Methods: The study included 157 patients diagnosed with subclinical hypothyroidism, categorised into anti-TPO-positive and anti-TPO-negative groups. A retrospective comprehensive evaluation comprising demographic data, thyroid medication status, ultrasonographic characteristics, and laboratory parameters was conducted and statistically analysed between the groups.

Results: Of 157 patients, 48.4% were anti-TPO positive. This group was significantly associated with increased levothyroxine (LT4) use and sonographic parenchymal heterogeneity. However, there were no significant differences in nodule presence, number, size, or structure. A positive correlation was found between anti-TPO and ferritin levels. In addition, a positive correlation was observed between the thyroid-stimulating hormone (TSH)/free T4 ratio and the solidity of nodules, as well as between TSH and the neutrophil-to-lymphocyte ratio (NLR). Surprisingly, a negative correlation was found between anti-TPO levels and the number of nodules, as well as the cystic characterisation of the nodules.

Discussion: In our study, higher levels of anti-TPO and TSH were associated with inflammatory markers such as ferritin and NLR, suggesting a possible link with systemic inflammation. Furthermore, anti-TPO and the TSH/T4 ratio also showed associations with specific sonographic features of the thyroid gland.

Conclusion: TSH and anti-TPO levels might be associated with systemic inflammation and thyroid sonographic findings in patients with subclinical hypothyroidism. More studies on larger patient populations should confirm the same results to suggest their clinical significance.

Systemic glucocorticoids are commonly prescribed in the management of COPD exacerbations; however, prolonged or repeated steroid use may lead to adrenal suppression. Although the standard steroid regimen for COPD exacerbations is short-term, frequent ED visits may result in cumulative steroid exposure, raising concerns about adrenal insufficiency and its clinical consequences.

This study investigates the potential association between steroid-induced adrenal suppression and frequent ED visits among COPD patients. It further examines the impact of steroid administration on cortisol and Adrenocorticotropic hormone (ACTH) levels.

Methods: This prospective, cross-sectional, observational study was conducted in a university- based ED. Patients with COPD, with dyspnea and who presented to the ED between 06:00-08:00 were included. Demographics, previous presentations to the ED, medications used, hormone levels, and other laboratory results were recorded.

Results: Fifty patients (82% were male) included. Sputum symptoms along with incidences of heart failure were higher in patients who received steroids in the ED. Ronchi was higher, crackles and pretibial edema were lower in the patients who received steroids in the ED. Among the patients with low cortisol levels, the frequency of patients who received steroids in the ED was higher than those who did not.

Conclusion: Primary healthcare clinicians should monitor COPD patients for potential adrenal insufficiency. Careful regulation of steroid dosages during exacerbation treatment and minimizing polypharmacy are essential to mitigate the long-term effects of prolonged steroid use.

Materials and Methods: The key active components of YPSXZJDD were screened using UHPLC- Q Exactive Orbitrap-MS, and a Protein-Protein Interaction (PPI) network diagram was constructed to explore potential mechanisms of action. The identified components were then utilized to intervene in both cellular and animal models of hyperuricemic nephropathy, evaluating their therapeutic effects and underlying mechanisms.

Results: Catalpol and Tanshinone IIA were identified as the key active components of YPSXZJDD. These compounds significantly mitigated renal epithelial cell apoptosis and inflammation by upregulating miR-223, which in turn inhibited the NLRP3/Caspase-1 pathway. The upregulation of miR-223 led to a marked reduction in NLRP3 activity and inflammatory responses, thereby alleviating HN-induced kidney damage.

Discussion: The findings of this study underscore the critical role of miR-223 in regulating the NLRP3 inflammasome and highlight its potential as a therapeutic target for HN. The inhibition of the NLRP3/Caspase-1 pathway by miR-223 significantly reduces inflammation and renal injury, demonstrating the therapeutic efficacy of YPSXZJDD. These results offer a novel perspective on the application of traditional Chinese medicine in treating HN, highlighting the importance of miR-223 in regulating inflammation.

Conclusion: This study demonstrates that YPSXZJDD alleviates HN-induced kidney injury by upregulating miR-223 and inhibiting the NLRP3/Caspase-1 pathway. The therapeutic potential of YPSXZJDD is supported by its ability to mitigate inflammation and renal damage, offering a promising approach for HN treatment. Further research into the broader role of miR-223 in kidney disease and related conditions is warranted to expand the understanding of its therapeutic applications.

Methods: Single-cell RNA sequencing (scRNA-seq) Data from 2 pre-B high hyperdiploid (HHD) ALL patients and 3 healthy pediatric bone marrow samples (GSE132509) were utilized for cell clustering using the Seurat package. Functional enrichment, pseudo-time trajectory, and cell-cell communication analyses were performed using clusterProfiler, Monocle2, and CellChat R packages, respectively. Bulk RNA-seq data of 511 cALL samples in the TARGET-ALL-P2 cohort were used to construct a prognostic model via Cox and LASSO regression. Immune infiltration differences between different risk groups were analyzed using ESTIMATE, MCP-counter, and CIBERSORT algorithms.

Results: The scRNA-seq analysis identified five cell subpopulations, with B cells demonstrating significant enrichment in cALL samples. Notably, the C2 subset was associated with cell proliferation. Ligand-receptor analysis revealed key interactions involving B cell C2. Four marker genes (CENPF, IGLL1, ANP32E, and PSMA2) were identified to build a risk model. Low-risk patients showed better survival, while high-risk patients had higher ESTIMATE scores.

Discussion: This study examined the key role of B cells in cALL, constructed a risk model with strong prognostic predictive ability applying multi-omics analysis, and primarily explored its potential mechanism in immune regulation.

Conclusion: This study revealed the critical role of B cells in cALL, and the prognostic model showed a high prediction accuracy, providing a potential target for individualized treatment of cALL.

Methods: AKI samples were acquired from Gene Expression Omnibus (GEO) database. AKI-related module genes were identified using the “WGCNA” package. The “Limma” package was used to filter Differentially Expressed Genes (DEGs). Protein interaction networks were constructed by intersecting key modular genes with DEGs, and six algorithms (MCC, MNC, Degree, EPC, Closeness, and Radiality) in the cytoHubba plug-in were combined to screen candidate genes. Diagnostic biomarkers were cross-screened using LASSO regression with Support Vector Machine–Recursive Feature Elimination (SVM-RFE) machine learning algorithm, and their predictive performance was verified by Receiver Operating Characteristic (ROC) analysis. Transcription Factors (TFs) regulatory network was constructed applying Cytoscape 3.8.0. Finally, the prediction and molecular docking analysis of potential target drugs were performed using the DSigDB database and AutoDockTools.

Results: A total of 498 key modular genes significantly associated with AKI were screened, and 88 AKI- related DEGs and 18 candidate genes were further identified. Importantly, four biomarkers with high diagnostic value (DDX17, FUBP1, PABPN1, and SF3B1) were screened and validated using dual machine learning algorithms, including LASSO regression and SVM-RFE. The area under the ROC curve (AUC) values for these biomarkers were greater than 0.8, indicating good predictive performance. Moreover, 19 TFs and 17 miRNA of SF3B1, 10 TFs and 58 miRNA of PABPN1, 15 TFs and 60 miRNA of FUBP1, together with 13 TFs and 109 miRNA of DDX17, were screened. Drug prediction and molecular docking analysis revealed that Demecolcine and Testosterone Enanthate stably bind to certain markers.

Discussion: Four potential biomarkers closely related to AKI were identified, which may be involved in the occurrence and progression of AKI by regulating key processes such as transcription. The predicted Demecolcine and Testosterone Enanthate may also be involved in the repair of renal injury by regulating key target genes. Although further experimental validation is still needed, these may still provide new intervention strategies for the treatment of AKI.

Conclusion: To conclude, four AKI biomarkers with high diagnostic value were screened by integrating multiple computational methods, revealing a new perspective on the molecular mechanism of AKI. The results provided a new theoretical basis for achieving early precision diagnosis and individualized treatment of AKI.

Objective: This review synthesizes mechanistic insights into DAMP signaling and regulated cell death modalities in IRI, aiming to identify translational gaps and propose precision-targeted therapies.

Methods: A literature search in PubMed using keywords “IRI,” “DAMPs,” and cell death modes was conducted without date restrictions. Peer-reviewed studies on human/animal models were included, with qualitative synthesis of DAMP-cell death interactions.

Results: During ischemia, mitochondrial dysfunction releases HMGB1, ATP, and mtDNA, activating Kupffer cell TLR4/RAGE and cGAS-STING pathways, triggering NLRP3 inflammasomedriven cytokine storms. Reperfusion amplifies ROS bursts, lipid peroxidation, and iron overload, creating a self-sustaining cycle of damage. Cell death modalities exhibit spatiotemporal specificity: hepatocyte ferroptosis dominates early injury, while macrophage pyroptosis and necroptosis predominate in steatotic livers during late phases. HMGB1 lactylation and mtDNA-cGAS signaling emerge as key regulators. Machine perfusion (e.g., hypothermic oxygenated perfusion) reduces biliary complications via mitochondrial resuscitation, outperforming conventional drugbased therapies.

Conclusion: Current single-pathway targeting shows limited efficacy due to IRI’s complexity. Future strategies should integrate temporal targeting (ferroptosis inhibitors pre-reperfusion; pyroptosis blockers post-reperfusion), DAMP-neutralizing agents (anti-HMGB1 antibodies), and precision preservation combining multi-omics biomarkers with ex vivo pharmacological preconditioning. Addressing metabolic vulnerabilities in fatty livers and refining cell death-specific interventions are critical for bridging translational gaps.

Case Presentation: A 48-year-old woman with poorly controlled type 2 diabetes developed necrotizing fasciitis of the right perineum secondary to an ischial tuberosity pressure ulcer. She had a prior spinal cord injury resulting in sensory dysfunction in the lower limbs, which masked significant pain. Management included surgical debridement, open wound care, antimicrobial therapy, and a free skin graft for wound closure.

Conclusion: Effective treatment of necrotizing fasciitis relies on aggressive debridement and appropriate antimicrobial therapy. This case highlights the importance of early recognition and intervention to improve clinical diagnostic and management strategies.

Objective: This study sought to explore the role and mechanism of esketamine in the LIR-ALI rat model.

Methods: The effects of esketamine on the LIR-ALI rats model were evaluated through histopathological examination, assessment of pulmonary edema, measurement of MDA and SOD levels, and analysis of inflammatory cytokine levels (IL-1β, etc.) in the bronchoalveolar fluid (BALF) and serum. Western blot analysis was used to assess the expressions of TLR4, NF-κB, and NLRP3. TLR4 agonist, LPS, was used to validate the role of NF-κB/NLRP3 pathway in LIRALI.

Results: Esketamine significantly alleviated LIR-induced ALI by reducing pulmonary edema, inflammatory cell infiltration, and oxidative stress. Elevated MDA content and suppressed SOD activity were significantly reversed by esketamine, along with inactivity of the TLR4/NF-κB/NLRP3 pathway. Esketamine treatment reduced inflammatory response in BALF and serum. TLR4 activation by LPS reversed the ameliorative effects of esketamine on LIR-ALI.

Conclusion: Esketamine protected against LIR-induced ALI by mitigating oxidative stress and suppressing the TLR4/NF-κB/NLRP3 axis. These findings highlight the potential therapeutic value of esketamine for ALI.

Background: Testicular cancer is a frequently diagnosed male tumor. Emerging evidence suggests that Copines family genes are implicated in a variety of cancer phenotypes and cancer progression. Analyzing the expression pattern of Copines family genes in testicular cancer may help improve the treatment efficacy of the cancer.

Objective: This study sought to characterize the expression profiles of Copines family genes in the cellular subpopulations of testicular cancer and to identify key signaling pathways through which they regulate cancer progression.

Methods: Based on single-cell transcriptomic data of testicular cancer, we classified testicular cancer cell subpopulations and analyzed the expressions of Copines family genes in each subpopulation. Cell subpopulations were grouped according to the expression levels of Copines family genes, and differentially expressed Copines family genes between the groups were screened by differential expression analysis. Functional enrichment analysis on the differentially expressed genes (DEGs) was performed with a clusterprofiler package. Functional pathways enriched by the Copines family genes were calculated by AUCell enrichment score. Copy number variation (CNV) analysis was performed using inferCNV to analyze gene mutation patterns across cellular subpopulations, and pseudotime analysis was conducted using Monocle to infer cellular differentiation pathways of cellular subpopulations.

Results: Single-cell clustering identified four major cell subpopulations, namely, NK/T cells, tumor cells, B cells, and macrophages. Notably, the control samples had a relatively small proportion of tumor cells. Further clustering of the tumor cells identified six cell subpopulations, among which multiple Copines genes, especially CPNE1 and CPNE3, showed a high expression. The testicular cancer samples were grouped by the expression patterns of Copines genes, and the DEGs between groups included GNLY, MGP1, CFD2, CCL21, SPARCL13 as well as some other genes involved in the malignant progression of cancer. Pseudotime analysis showed that the upregulated genes were enriched in cell migration and PI3K-Akt pathway, while the downregulated genes were related to immunity. This indicated that the Copines genes regulated the cellular heterogeneity and malignant transformation in testicular cancer.

Conclusion: This study revealed the potential molecular mechanism through which Copines family genes drove the progression of testicular cancer through regulating PI3K-Akt signaling pathway and cell cycle, providing a new target for the development of precision treatment targeting Copines family genes and prognostic assessment of the cancer.

Methods: Appropriate single nucleotide polymorphisms (SNPs) were carefully selected from publicly available GWAS databases based on rigorous criteria to ensure the validity of the Mendelian randomization (MR) analysis. Inverse variance weighting (IVW) was employed as the primary approach for assessing effect sizes, supplemented by four sensitivity analysis techniques: weighted median, simple mode, weighted mode, and MR-Egger regression tests, all aimed at ensuring the robustness and reliability of the IVW results. Reverse MR was conducted to confirm the feasibility of the mediation analysis. Lastly, Cochran’s Q test, MR Egger intercept regression, and MR-PRESSO analysis were utilized to examine heterogeneity and horizontal pleiotropy.

Results: The expression of BDH1 is inversely associated with the risk of type 2 diabetes, with an odds ratio of 0.97 (95% CI: 0.95-0.99). IgD+ CD38+ B cell absolute count (20.7%), HLA DR on dendritic cell (18.7%), BAFF-R on CD20- CD38- B cell (9.5%), CD25 on IgD⁺ CD24⁺ B cell (4.1%), and BAFF-R on IgD+ B cell (3.4%), all exhibit certain mediating effects, whereas IgD+ CD38⁺ B cell absolute count, activated and resting CD4 regulatory T cell %, CD4⁺ T cell, transitional B cell absolute count, CD28- CD8 dim T cell absolute count, CD45 on HLA DR⁺ CD8⁺ T cell, FSC-A on HLA DR⁺ natural killer, and SSC-A on plasmacytoid dendritic cell exert masking effects.

Conclusion: The findings indicate that immunocytes could serve as a crucial mediating mechanism through which BDH1 exerts its protective effect against type 2 diabetes, offering novel insights for the prevention and therapeutic management of the disease.

Methods: A retrospective cross-sectional analysis was conducted using data from 502 patients. Glycemic control was assessed based on HbA1c levels, and serum magnesium concentrations were evaluated concerning clinical and demographic variables. Statistical analyses included ttests, Mann-Whitney U tests, logistic regression, and ROC curve analysis.

Results: Patients with poor glycemic control had significantly lower serum magnesium levels. Magnesium levels were lower in females, particularly postmenopausal women. Magnesium levels were significantly associated with hypertension, gender, and the use of specific medications such as metformin and indapamide. Logistic regression revealed a significant inverse association between serum Magnesium levels and congestive heart failure (OR = 0.055), but not with other comorbidities. ROC analysis revealed limited predictive value of magnesium for glycemic control (AUC = 0.41).

Discussion: Although group-level differences in magnesium were evident, magnesium levels alone were not reliable predictors of glycemic control. However, the associations with CHF, HT, gender, and specific medications suggest that magnesium plays a multifaceted role in type 2 diabetes mellitus management.

Conclusion: Regular monitoring of serum magnesium may aid in identifying at-risk patients, especially those with hypertension, CHF, or on magnesium-depleting medications. Further prospective studies are needed to clarify the clinical utility of magnesium in diabetes care.

Materials and Methods: JTD's targets were cross-matched with genes associated with T2DM or NAFLD. SMR and co-localization analyses, utilizing eQTL and pQTL data, identified causal signals for each disease and their shared counterparts. GO/KEGG enrichment analyses were performed on these shared signals. Molecular docking assessed binding interactions. In vitro experiments, including ELISA (Enzyme-linked immunosorbent assay) and lipid staining, evaluated JTD's hypoglycemic/hypolipidemic effects, while PCR/immunofluorescence validated key molecular predictions in High-Glucose and High-Lipid (HGHL)-induced HepG2 cells.

Results: Initial network pharmacology identified 1107 JTD targets for T2DM and 1126 for NAFLD. SMR analyses revealed 78 eQTLs and 67 pQTLs for T2DM, and 40 eQTLs and 38 pQTLs for NAFLD. Eight shared causal genetic signals were identified: ADAMTS4, ALDH2, GLO1, CDH1, PDHB, PRKAB1, TCF4, and EP300. In vitro, JTD significantly attenuated hepatic gluconeogenesis and lipid deposition, downregulated IL-1β, and notably restored PRKAB1 expression in HepG2 cells treated with HGHL.

Discussion: Enrichment analysis revealed shared processes, including membrane microdomains, oxidoreductase activity, and responses to nutrient and oxygen levels. PRKAB1 exhibited a strong binding affinity with the JTD component Salsalate.

Conclusion: This study identified eight genes that are genetically predicted to be causal for the therapeutic effects of JTD on both T2DM and NAFLD, thereby establishing a genetic link between the conditions. These targets and associated pathways illuminate common underlying mechanisms, supporting JTD's potential for integrated treatment strategies and providing a basis for further investigation.

Methods: Using Genome-Wide Association Study (GWAS) summary data, we conducted both univariate and multivariable Mendelian Randomization (MVMR) analyses. The primary causal inference was based on Inverse Variance Weighted (IVW), MR-Egger, weighted median, and sensitivity analyses (Cochran’s Q, MR-PRESSO). Mediation analysis was employed to quantify the proportion of effects operating through metabolite-regulated pathways.

Results: BMR was inversely associated with hyperemesis gravidarum (OR=0.73, 95% CI: 0.59-0.90, P=0.008), Intrahepatic Cholestasis of Pregnancy (ICP) (OR=0.67, 95% CI: 0.56-0.80, P<0.001), poor fetal growth (OR=0.80, 95% CI:0.71-0.90, P=0.001), and preterm delivery (OR=0.78, 95% CI:0.70-0.87, P<0.001). MVMR identified elevated BMR and mannose levels as protective against ICP, with BMR showing a positive correlation with mannose. Mediation analysis revealed that BMR reduced ICP risk partly through increased mannose (OR = 1.38, 95% CI: 1.19-1.59, P = 2.03 × 10⁻⁵), accounting for 29.93% of the effect.

Discussion: Elevated BMR significantly reduced risks of intrahepatic cholestasis (HR=0.67), fetal distress (HR=0.80), and preterm birth (HR=0.78), mediated partly by mannose levels. Mendelian randomization established causality, linking metabolic adaptation to improved pregnancy outcomes. However, these findings, based on European genetic data, limit generalizability, and unmeasured confounders may persist despite MR methods.

Conclusion: Higher BMR may lower risks of hyperemesis gravidarum, ICP, poor fetal growth, and preterm delivery. Mannose mediates the protective effect of BMR on ICP, highlighting potential metabolic pathways for intervention.

Methods: Summary statistics for 179 lipid species across 13 classes were retrieved from the GWAS Catalog, encompassing 7,174 Finnish individuals from the GeneRISK study. For AF, data were synthesized from six major studies comprising over one million subjects. Our Two-Sample MR (TSMR) approach was implemented using Inverse Variance Weighting (IVW), MR-Egger, and MR-PRESSO for sensitivity analysis. Additionally, we uniquely integrated the Mendelian Randomization-Bayesian Model Averaging (MR_BMA) method to robustly prioritize the most likely causal lipid determinants of AF, and performed bidirectional MR analysis to assess potential reverse causality.

Results: The TSMR analysis, reinforced by MR_BMA, revealed significant causal associations between specific lipid species and AF risk. In particular, Phosphatidylcholine (17:0_18:2) was associated with a decreased risk of AF (OR = 0.96, 95% CI 0.93–0.99, P<0.05), whereas Phosphatidylcholine (16:0_20:5) and Phosphatidylcholine (17:0_20:4) were linked to increased risks (OR = 1.04, 95% CI 1.01–1.07, P<0.01; and OR = 1.02, 95% CI 1.00–1.05, P<0.05, respectively). Furthermore, elevated levels of Phosphatidylethanolamine (18:0_20:4) (OR = 1.03, 95% CI 1.01–1.06, P<0.01) and Triacylglycerol (50:4) (OR = 1.04, 95% CI 1.00–1.07, P<0.05) were also associated with increased AF risk. In addition, Sphingomyelin (d34:2), Sterol ester (27:1/18:0), and Sterol ester (27:1/18:3) emerged as further risk factors, thereby expanding the spectrum of lipidomic determinants implicated in AF. The bidirectional MR analysis provided no evidence of reverse causation, reinforcing the directionality of the lipid-driven association. Sensitivity analyses demonstrated robust findings with no indication of pleiotropy or heterogeneity.

Conclusion: This study provides strong evidence for the causal role of specific lipid species in the development of AF. Our comprehensive MR analysis not only deepens our understanding of AF pathophysiology but also highlights the therapeutic potential of targeting these lipid alterations. Notably, the absence of reverse causation supports a unidirectional relationship wherein altered lipid species drive AF risk.

Methods: MethylTarget™ sequencing targeted AIM2 cg11003133 (chr1:159076528-159076740) in RA, Ankylosing Spondylitis (AS), Psoriatic Arthritis (PsA), gout, Systemic Lupus Erythematosus (SLE), Dermatomyositis (DM), primary Sjögren's Syndrome (SS), and Healthy Controls (HC) patients. Logistic regression, random forest, and XGBoost models were applied, with Spearman’s correlation used to assess associations.

Results: RA and RF/CCP-positive patients showed significantly higher methylation at cg11003133_79/91 compared to HC and AS (FDR < 0.05), but lower levels compared to DM. Methylation at cg11003133_139 was elevated in RA compared to AS/SS (FDR = 0.04/0.03). Anti- TNF-α non-responders had higher cg11003133_79/91 methylation levels compared to HC/AS non-responders (FDR < 0.05). RF-negative RA patients had higher cg11003133_91 methylation than AS patients who failed anti-TNF-α treatment (FDR < 0.05). Haplotype CCCC correlated positively with CRP (r = 0.14, P = 0.006); TTTT was significantly negatively correlated with erythrocyte sedimentation rate, CRP, and the presence of diabetes (r = -0.18, -0.15, and -0.14; P < 0.001, 0.003, and 0.008, respectively). XGBoost and RF models achieved AUCs of 0.9911 and 0.9975 for RA versus non-RA, and 1 for RF/CCP double-negative versus double-positive RA.

Discussion: AIM2 cg11003133 methylation is strongly linked to RA, aligning with its role in inflammasome activation. While promising for diagnostics, larger validation is needed.

Conclusions: AIM2 cg11003133 methylation may serve as a diagnostic biomarker for RA and subtypes.

Aims and Objectives: This study aimed to explore the prognostic factors associated with nitrogen metabolism in bladder cancer (BC) and to construct a prognostic model.

Methods: Differential expression gene analysis was performed to identify genes associated with nitrogen metabolism by analyzing mRNA expression data from BC patients. The prognostic relationship between these genes and BC patients was analyzed using univariate Cox regression. One hundred one combinatorial machine learning methods were applied for feature selection, and key prognostic genes were identified based on the method with the highest combined score. Immunocyte infiltration analysis was carried out to assess the tumor microenvironmental characteristics of patients in different risk groups.

Results: Twenty-five genes significantly associated with prognosis were identified from nitrogen metabolism-related genes. Twenty-three most prognostically predictive signature genes were screened under feature screening with multiple machine-learning models. Immune cell infiltration analysis showed that patients in the high-risk group had significantly different immune cell infiltration, suggesting that these genes may influence BC progression by regulating immune escape mechanisms. These results provide new biomarkers and potential therapeutic targets for precision treatment and prognostic assessment of BC.

Discussion: The findings suggest that nitrogen metabolism-related genes play a key role in the prognosis of bladder cancer and may be involved in regulating the tumor immune microenvironment. Different immune environments were demonstrated in high and low Riskscore groups, implying that these genes may contribute to immune evasion and thus promote tumor progression. These observations are consistent with emerging evidence that emphasizes the interplay between metabolism and immunity during cancer development. By combining nitrogen metabolism with immune analysis, this study provides a new perspective for stratifying BC patients and identifying therapeutic targets.

Conclusion: The expression patterns of nitrogen metabolism-related genes identified can be used as effective biomarkers for bladder cancer prognosis, providing a scientific basis for personalized treatment. Future studies can further explore the specific biological functions and mechanisms of action of these genes to promote more effective clinical applications.

Methods: Primary human orbital preadipocytes were chosen and authenticated using immunofluorescence. Cells were treated with the IGF-1R agonist ginsenoside Rg5, IGF-1R overexpression plasmid, dexamethasone (Dex), and/or DA, after which cell proliferation and differentiation were assessed by cell counting kit-8 (CCK-8), oil red O staining, real-time quantitative polymerase chain reaction, and Western blot assays.

Results: Orbital preadipocytes showed positive expression of Pref-1. Treatment with IGF-1R agonist, as well as Dex, promoted orbital adipocyte viability and lipid accumulation, and increased the expression of adiponectin and leptin. It was observed that the overexpression of IGF-1R boosted PI3K/AKT activation and elevated PPARγ and C/EBPα expressions. Importantly, DA reversed the effects of IGF-1R on cell viability, lipid accumulation, and the PI3K/AKT signaling pathway.

Discussion: This study, for the first time, revealed the molecular mechanism by which DA regulates orbital fat metabolism through targeted inhibition of the IGF-1R/PI3K/AKT signaling axis. Notably, IGF-1R overexpression partially counteracted the inhibitory effect of DA, suggesting that this component has multi-target regulatory characteristics.

Conclusion: This study not only reveals a new mechanism by which DA treats TAO but also provides theoretical support for the treatment of adipose metabolism.

Case Presentation: We provide the first complete case of Graves' disease with ICPi therapy in a patient who already had Hashimoto's thyroiditis. The patient, a 52-year-old male, was diagnosed with lung adenocarcinoma and received Atezolizumab. Clinical evaluation revealed hyperthyroidism, confirmed by elevated thyroid hormones and autoantibodies (TRAb and TSAb). The patient was managed with methimazole and demonstrated a transient hyperthyroid phase followed by persistent hypothyroidism. Only 16 confirmed cases of Graves' disease induced by ICPi were reported. We conducted a review to investigate the clinical characteristics, risk factors, and prognosis trends associated with ICPi-induced Graves disease in PTAD patients. Additionally, changes in thyroid function and autoantibodies during and after ICPi treatment are examined.

Conclusion: This case underscores the importance of monitoring thyroid function and autoantibodies in patients with PATD undergoing ICPi therapy. The findings suggest distinct differences in the humoral immune response between ICPi-induced and spontaneous Graves' disease, necessitating further research into autoantibody dynamics and their relationship with cellular immunity in these patients.

Aims: The aim of this study was to discover common diagnostic genes for LUAD and MI and analyze their molecular functions and potential drug values by applying bioinformatics analysis.

Objective: The objective was to provide a theoretical basis for further research on the pathological mechanisms of LUAD and MI, contributing to the development of novel diagnostic and therapeutic strategies for the two diseases.

Methods: In this study, the datasets of LUAD and MI were obtained from TCGA and GEO databases, and differential expression analysis was performed to screen significantly differentially expressed genes (DEGs). Subsequently, disease-related genes were identified using WGCNA analysis, and the biological functions of these genes were explored by functional enrichment analysis. After screening key genes using the protein-protein interaction (PPI) network and the cytoHubba algorithm, biomarkers were determined by LASSO and SVM-RFE machine-learning methods. Finally, immune infiltration analysis and drug prediction were performed, and biomarker expression was verified by single-cell sequencing analysis.

Results: A total of 158 differentially upregulated genes were identified between LUAD and MI. WGCNA analysis screened 86 genes that were significantly associated with both diseases and were enriched in an inflammatory response and immune regulation-related pathways, such as the IL-17 signaling pathway. Ten significant genes were identified by the PPI network and cytoHubba and then reduced to 4 using LASSO and SVM-RFE. Noticeably, MMP9 was significantly overexpressed in both diseases. Immune infiltration analysis showed that MMP9 was significantly related to multiple immune cell infiltration. Drug prediction and molecular docking analysis predicted Ilomastat and Osthole as the potential target drugs. Single-cell sequencing analysis revealed that MMP9 was high-expressed in the macrophages in LUAD tissues.

Conclusion: This study identified MMP9 as a common diagnostic gene and potential therapeutic target for both LUAD and MI and revealed its role in inflammation and immune regulation through comprehensive bioinformatics analysis. These findings provided a theoretical basis for further research on the pathological mechanisms of LUAD and MI, contributing to the development of novel diagnostic and therapeutic strategies.

Background: FM is a chronic disease featuring widespread pain, and the immune system may be involved in the FM progression.

Objective: The objectives of this study are as follows: 1) To identify the molecular subtypes of FM based on IRGs. 2) To screen and validate the hub genes in FM. 3) To predict the transcription factor (TF) targeting hub genes and 4) To evaluate the correlation between immune cell infiltration, hallmark pathways, and hub genes.

Methods: Two FM datasets were acquired from the Gene Expression Omnibus (GEO) database. IRGs were collected from the ImmPort database. Molecular subtypes of FM were identified using the “ConsensusClusterPlus” package. IRGs score and differentially expressed genes (DEGs) between different FM subtypes and control samples were obtained using “GSVA” and “limma” packages. Key module genes related to FM subtypes were identified using the “WGCNA” package. Hub genes were screened and verified using “glmnet” and “pROC” packages. TF-hub gene regulatory network was constructed by Cytoscape software. The correlation between immune cells, hallmark pathways, and hub genes was analyzed by the Spearman method. Finally, the DSigDB database was used to obtain associations between characterized genes and drugs, and the expression of key genes was verified using qRT-PCR.

Results: FM samples were classified into two subtypes, and the IRGs score of the C2 subtype was lower than that of the C1 subtype. Then, 184 module genes were obtained and mainly enriched in immune-related pathways. Next, 11 hub genes (TSPAN16, RILPL2, RASSF5, PGAP2, PADI2, NACC1, LRRC25, ITGAD, HIPK1, ATP6V0D1, AP1M2) were screened with good diagnostic performance. Besides, 45 TFs targeting hub genes were predicted. Most hub genes were negatively associated with CD4/CD8 T cells while positively correlated with macrophages, mast cell, monocyte, and neutrophil, as well as inflammatory response, angiogenesis pathways, etc. Molecular docking suggests that chloroquine and L-citrulline may be potent agents binding to NACC1 and PADI2. RILPL2 and ITGAD were significantly differentially expressed in FM-modeled mice.

Conclusion: This study identified two subtypes and 11 hub genes of FM based on IRGs, providing a reference for the clinical diagnosis of FM.

Aims: This study explored the mutation status of DRGs in CESC.

Objective: After analyzing the mutation profiles of DRGs in CESC, this study established a prognostic model for CESC and also explored the differences in immune infiltration (accumulation of immune system cells in tissues or organs), related enriched pathways, and drug sensitivity between high-risk and low-risk CESC groups.

Methods: The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) were accessed to source related data. The mutation profiles of DRGs in CESC were analyzed using Mutect2 software, and disulfidptosis scores were calculated by ssGSEA. WGCNA was performed to identify modular genes, which were further filtered and used to formulate a risk model by applying the survival and glmnet packages. Low- and high-risk groups of CESC patients were classified using the survminer package. GSEA was performed to conduct pathway analysis, and immune infiltration was assessed using the MCPcounter package, ESTIMATE, and TIMER algorithms. Finally, immunotherapy response and drug sensitivity were analyzed using the TIDE method and the pRRophetic package, respectively.

Results: Except for NDUFA11, ARL6IP5, EPM2AIP1, GBE1, RBM38, ULK4, and ZBTB47 were found to be the DRGs significantly mutated in CESC. The six genes were integrated to develop a RiskScore model with a relatively high Area Under the Curve (AUC) value. Significant differences between the two risk groups were determined, indicating that the model was highly reliable. Notably, the low-risk group was enriched in energy metabolism-correlated pathways, while the high-risk group was primarily enriched in immune-correlated pathways. The high-risk group showed higher immune cell activity, higher TIDE score, and more B cells than the low-risk group. Drug sensitivity study revealed that the high-risk group was more sensitive to chemotherapy drugs.

Conclusion: This study provides novel insights into CESC prognosis, immunotherapy, and drug development, contributing to the clinical treatment for CESC.

Methods: We established a rat model of HFpEF using Dahl salt-sensitive rats and evaluated three experimental groups: control (A), HFpEF (B), and canagliflozin-treated HFpEF (C). This study carried out comprehensive analyses of cardiac structure and function, metabolomic profiling, and detailed assessment of myocardial energy metabolism, including mitochondrial respiratory capacity and ATP synthesis. Additionally, we validated our findings using H9C2 cardiomyocytes under controlled conditions.

Results: Canagliflozin treatment significantly improved cardiac remodeling markers, including reduced myocardial volume and fibrosis area, while enhancing diastolic function (E/A ratio). Metabolomic analysis revealed normalization of hypermetabolic states, with significant reductions in key metabolites, including L-lysine, D-glucose, and uridine. The treatment restored balance in multiple metabolic pathways, particularly affecting β-alanine metabolism, pyrimidine metabolism, and the citrate cycle. Notably, canagliflozin enhanced mitochondrial respiratory function, increased ATP synthesis, and optimized fatty acid utilization, as evidenced by reduced free fatty acid content.

Conclusion: Our findings demonstrated that canagliflozin exerts cardioprotective effects through multiple metabolic pathways, suggesting its potential as a therapeutic option for HFpEF. The ability of the drug to optimize energy metabolism and improve mitochondrial function represents a novel mechanism for treating this challenging condition.

Methods: Articles concerning children with MAFLD published from 2014-2023 were identified from the Science Citation Index-Expanded of the Web of Science Core Collection. CiteSpace software, VOSviewer, and the Online Analysis Platform of Literature Metrology were used to analyze the current publication trends and hotspots.

Results: The analysis identified 1,609 English-language articles on pediatric MAFLD published from 2014 to 2023. The United States emerged as the most active participant in international collaborations. The University of California San Diego (UCSD) demonstrated the highest research output among the analyzed institutions. Additionally, UCSD exhibited the most extensive collaborative network, engaging in frequent and substantive research partnerships with a diverse range of academic and scientific organizations. Valerio Nobili was found to be the most prolific author, with 67 articles. Keyword burst analysis revealed that cardiovascular risk factors were the most intense research hotspot.

Conclusion: Current research on pediatric MAFLD warrants greater attention, particularly regarding cardiovascular risk factors. This study provides valuable references for researchers, offering insights to guide future research directions and potential collaborations.

Objective: Chinese medicines have been used effectively in the treatment of infectious disorders; thus, this study aimed to investigate the efficiency of Chinese medicine against S. aureus.

Methods: An extract of traditional Chinese medicine was prepared using nine compounds: tongcao, talc, red peony root, fennel, guangui, lychee core, dry sunflower, dianthus, and purslane, to evaluate its antibacterial activity against Staphylococcus aureus RN450RF.

Results: The minimum inhibitory concentration (MIC) of the Chinese medicine measured by the consecutive double dilution technique was 200g/L. The drug-resistant plasmid was transferred equally well under controlled laboratory conditions with a median conjugation frequency of 1.1x10⁶. The maximum activity of conjugated transfer of resistant drug plasmid of E. coli CP9 (R45) was observed at 2/1 MIC (100 g/L drug concentration), 32h time interval, with a bacterial concentration 10⁸ CFU/ml.

Conclusion: These results suggest that the secondary inhibitory concentration (1/2 MIC) of the Chinese medicine solution can promote the combination and transfer of the resistance plasmid of Chinese medicine (R45) between different strains. The drug concentration, binding time, and initial bacterial concentration have different degrees of positive promotion effects on the conjugation and transfer of drug-resistant plasmids. Traditional Chinese medicine might be a potentially huge disease management and infection control resource.

Methods: We thoroughly searched the Science Citation Index-Expanded (SCI-E) of the Web of Science Core Collection (WoSCC), PubMed, and the Excerpta Medica Database (Embase) to identify relevant articles on the links between NASH and DM from 2004 to 2023. The current publication trends and hotspots in this field were analyzed using the Online Analysis Platform of Literature Metrology, CiteSpace software, VOSviewer, and the R package Bibliometrix.

Results: From 2004 to 2023, 943 articles were found that focused on the links between NASH and DM with a noticeable surge in publications since 2015. The United States has taken the primary position in terms of the number of publications. It has also been the most active country in international collaborative efforts. The University of California, San Diego, and Kenneth Cusi were the most productive institution and scholar, respectively. The co-citation keywords cluster labels revealed 10 primary clusters: adiponectin, MAFLD, mortality, NASH, nonalcoholic fatty liver, SGLT2, neurodegeneration, LY2405319, autophagy, and hepatocytes. Recent studies focused on weight loss, fibrosis stage, NAFLD, mortality, and diabetes mellitus.

Discussion: Research on NASH and DM has transitioned from early mechanistic exploration to a current focus on weight management, diabetes control, and fibrosis prevention, particularly through lifestyle interventions and antidiabetic drug therapy. Future studies should integrate lifestyle adjustments with drug development, enhance international cooperation to fill regional research gaps, and achieve more effective management of NASH and DM.

Conclusion: Over the past 20 years, global publications on the relationship between NASH and DM have grown rapidly. The current research hotspots focus on weight loss, and the reduction of blood glucose and fibrosis in NASH. Maintaining a healthy diet, exercising regularly, taking appropriate medication, and being vigilant about complications are essential for delaying the progression of NASH and DM. These are also the primary future directions of research.

Registration Number: Registration number: 1020973(PROSPERO)

Methods: Data were obtained from the European FinnGen biobank and the Gene Expression Omnibus (GEO) database. Mendelian Randomization (MR) analysis was performed with instrumental variables (IVs). The study assessed causal robustness using MR methods and sensitivity analysis, followed by differential expression analysis and weighted gene co-expression network analysis (WGCNA) to screen for the core genes. Further, machine learning algorithms, such as least absolute shrinkage and selection operator (LASSO), random forest (RF), and support vector machine (SVM) algorithms, were applied to screen for key diagnostic genes. Additionally, the CIBERSORT algorithm was used to analyze immune cell infiltration, and validation was conducted using an in vitro oxidized low-density lipoprotein (ox-LDL)-induced endothelial cell model and western blot experiments.

Results: MR analysis revealed a positive causal link among vitamin B12 deficiency anemia, hemolytic anemia, and coronary heart disease, while cardiovascular events appeared to have a negative association with hemolytic anemia. Integrated bioinformatics analysis identified six core genes involved in immune response, inflammation, and lipid metabolism. To improve the accuracy of key gene screening and avoid bias from a single method, this study combined multiple machine learning algorithms for comprehensive analysis, ultimately identifying IFIH1 and APBB2 as potentially valuable diagnostic biomarkers, and revealing affected macrophages, mast cells, and T cells infiltration. In vitro experiments confirmed altered expression of IFIH1 and APBB2 upon ox-LDL treatment, supporting their role in CHD pathogenesis.

Discussion: The findings of this study suggest that vitamin B12 deficiency anemia and hemolytic anemia are potential risk factors for CHD. The identification of IFIH1 and APBB2 as key biomarkers provides novel insights into the molecular mechanisms underlying CHD development in the context of anemia, offering potential targets for early diagnosis and personalized intervention strategies.

Conclusion: This study, through the integration of MR, transcriptomics, and machine learning methods, has for the first time revealed the causal role of vitamin B12 deficiency anemia and hemolytic anemia in the occurrence of CHD, and identified IFIH1 and APBB2 as potential biomarkers. This research study has provided a new theoretical basis and research direction for understanding the molecular link between anemia and CHD and for improving clinical early warning systems.

Methods: This cross-sectional study included adult participants from the 2007-2018 National Health and Nutrition Examination Survey (NHANES). The RFM was calculated as: RFM =64 - (20 × height/waist circumference) + (12 × sex), where sex is defined as 0 for men and 1 for women. Hyperuricemia was confirmed by using serum uric acid (SUA) levels ≥ 7 mg/dL in men and ≥ 6 mg/dL in women. The relationship between RFM and the risk of hyperuricemia was thoroughly investigated.

Results: A total of 29369 participants were enrolled in this study. The RFM levels in the hyperuricemia group were higher than those in the non-hyperuricemia group (P < 0.01). Logistic and linear regression indicated that RFM levels were positively associated with the risk of hyperuricemia (OR=1.08, 95% CI: 1.05-1.11, P < 0.001) and SUA levels (β=0.04, 95% CI: 0.03-0.05, P < 0.001). The relationship remained consistent across subgroups. Smooth curve fitting showed a nonlinear relationship, with an inflection point at 34.22. Above this threshold, the link between RFM levels and hyperuricemia was found to be more remarkable.

Conclusion: Higher RFM is associated with an increased risk of hyperuricemia. RFM could act as a cost-efficient and straightforward measure for hyperuricemia risk assessment.

Methods: The GSE122897 and GSE75436 datasets were obtained from the Gene Expression Omnibus (GEO) database. Senescence and inflammation scores were calculated using single-sample GSEA (ssGSEA), and weighted gene co-expression network analysis (WGCNA) was performed to identify relevant modules and hub genes. Differentially expressed genes (DEGs) were determined with the DESeq2 package, followed by conducting LASSO regression and support vector machine-recursive feature elimination (SVM-RFE) to screen key genes. Immune infiltration was analyzed using CIBERSORT and ESTIMATE algoritms, and correlations between key genes and immune cells were assessed. Finally, transcription factor (TF)-miRNA regulatory networks were constructed using the JASPAR package and ENCORI database.

Results: IA samples exhibited significantly higher senescence and inflammation scores in comparison to the controls. A total of 858 hub genes identified by WGCNA were intersected with the DEGs for further refinement by LASSO and SVM-RFE, ultimately yielding PTCH1, ACACB, DRD1, and SLC25A21-AS1 as the candidate genes for IA. Immune infiltration analysis showed that the expression of these genes was associated with several immune cells, including NK cells. Moreover, IA samples had higher ESTIMATEScore, ImmuneScore, and StromalScore, which were all negatively correlated with the expression of the four genes. TF-miRNA network analysis revealed 67, 71, and 76 potential TF regulators for PTCH1, ACACB, and SLC25A21-AS1, respectively.

Discussion: These findings indicated that senescence and inflammation contributed to IA pathogenesis and may regulate disease progression by modulating the immune microenvironment, highlighting their dual role in IA.

Conclusion: PTCH1, ACACB, and SLC25A21-AS1 were identified as potential biomarkers associated with senescence and inflammation in IA, providing novel insights into its molecular mechanisms and potential diagnostic or therapeutic targets.

Objective: This case-control study, conducted at a tertiary care center, aimed to elucidate the relationship between obesity and the degree of obesity, thyroid autoimmunity, and TFTs in euthyroid individuals with a BMI >30 kg/m² and explore variations based on the degree of obesity.

Methods: Free thyroid hormones, TSH, thyroid peroxidase antibodies (anti-TPO), anti-thyroglobulin antibodies (Anti-Tg), and metabolic parameters (glucose, lipid profile, insulin resistance, hemoglobin A1c) were measured in 164 euthyroid patients with obesity and 73 lean subjects aged 18-65 years. Subjects with obesity were stratified into three groups based on body mass index (BMI): first-degree obesity (BMI 30-34.9 kg/m²), second-degree obesity (BMI 35-39.9 kg/m²), and third-degree obesity (BMI ≥ 40 kg/m²).

Results: The prevalence of thyroid antibody positivity was significantly higher in the obese group compared with the non-obese group, specifically for anti-TPO (45 (27.4%) vs. 7 (9.6%) and anti- Tg (35 (21.3%) vs. 5 (6.8%). Anti-Tg titers were elevated in the obese group (p=0.006), but anti- TPO levels were similar across the groups. Among the BMI-stratified groups, individuals with first and second-degree obesity exhibited higher anti-TPO positivity and anti-Tg titers compared with the control group. No significant differences were found in the third-degree obesity group. TSH and fT4 levels were higher in the obese group compared with the non-obese group (p=0.016 and p=0.045, respectively), whereas fT3 levels and the fT3/fT4 ratio remained consistent across the groups. Although no direct correlation was found between thyroid autoantibodies and metabolic parameters, individuals positive for anti-TPO and/or anti-Tg exhibited worse metabolic profiles compared with individuals who were antibody-negative.

Conclusion: There is an increase in thyroid autoimmunity among euthyroid individuals with obesity; however, this increase does not appear to be proportional to BMI. The effect of antibody presence on metabolic parameters in individuals with obesity is not yet fully understood.

Methods: In this study, a rat model of SAP was established, and the rats were divided into three groups for treatment: the Control group (CON), the SAP group (SAP), and the SAP group treated with JZL184 (JZL184). The serum levels of amylase (AMS), alanine aminotransferase (ALT), creatinine (Cr), nitric oxide (NO), cyclic guanosine monophosphate (cGMP), and phosphodiesterase (PDE) were measured using enzyme-linked immunosorbent detection kits. The ascites volume was determined using the cotton ball weighing method. The levels of reactive oxygen species (ROS) were detected using the ROS Kit. Additionally, histological tissue changes were assessed through hematoxylin and eosin staining.

Results: The SAP group showed increased levels of AMS, ALT, Cr, ROS, and ascites volume compared to the CON group. Additionally, the SAP group exhibited congested and edematous lung and pancreatic tissues with inflammation. However, the JZL184 group, when compared to the SAP group, showed decreased levels of AMS, ALT, Cr, and ROS, reduced ascites volume, and significantly reduced lung tissue and pancreatic histopathology scores. In the NO/cGMP/PDE system, compared with the CON group, the levels of NO and PDE in the SAP group were higher and the levels of cGMP were lower. Compared with the SAP group, the JZL184 group decreased NO and PDE levels and increased cGMP levels.

Conclusions: Indeed, the inhibition of MAGL with JZL184 has been found to have a protective effect on rats with SAP. Specifically, it has shown significant improvement in the pathological damage of lung and pancreatic tissues. Furthermore, JZL184 has also exhibited protective effects on the liver and kidney. The mechanism may be related to the effect of JZL184 on the NO/cGMP/ PDE signaling pathway.

Materials and Methods: Whole-blood scRNA-seq samples from four septic patients and five healthy subjects were collected from the Gene Expression Omnibus (GEO) database (GSE175453). The Seurat R package was used for quality control and cell clustering by scRNA- seq analysis. Gene set enrichment analysis (GSEA) was performed using the clusterProfiler R package for pathway enrichment analysis. Then, the SCENIC analysis was used to identify key transcriptional regulons, and the CellChat R package was used for cell communication analysis.

Results: We mainly obtained 9 cell clusters, including myeloid cells, T cells, dendritic cells, NK T cells, B cells, plasma B cells, megakaryocytes, mast cells and erythrocytes. Notably, myeloid cells, erythrocytes and mast cells had a higher proportion in sepsis patients. Activated IL-17 and p53 pathways supported anti-infection response in myeloid cells, and JUNB and SPI1 mediated multiple inflammatory pathways, including TNF signaling and neutrophil activation. We also identified that the cell interaction mode of myeloid cells, such as MPZL1-MPZL1 and FASL-FAS, may serve as a potential target for an anti-inflammatory response in sepsis treatment.

Discussions: The scRNA-seq analysis revealed pro-inflammatory pathways (IL-17, p53) and key regulators (JUNB, SPI1) in septic myeloid cells. Receptor genes (MPZL1 and FAS) mediated cell communication, offering potential biomarkers and targets for sepsis therapy.

Conclusion: We characterized the pro-inflammatory immune response pathways, transcriptional regulon and cell interaction modes of myeloid cells in the development of sepsis.

Aims: This study aimed to present a bibliometric overview and visualization analysis of the existing studies examining the relationship between KD and ageing, identify trends in this field, and provide a basis for future research and sustainable development goals.

Materials and Methods: This study involved a systematic review of the literature. In this study, Scopus (Elsevier) and Web of Science Core Collection (WoSCC) databases were used for bibliometric analysis. In the study, all articles, reviews, and other types of publications on KD and ageing published between 1995 and 2024 were analysed. Studies covering the years 1995-2025 and including the keywords ‘ketogenic diet OR ketogenic diets OR ketone diet AND aging AND PUBYEAR > 1995 AND PUBYEAR < 2025' in the title were included. The VOSviewer software (VOSviewer v.1.6.10) was utilized to visualize the data. The data obtained were evaluated by bibliometric methods, such as keyword analysis and cluster analysis.

Results: A significant increase in the number of studies on KD and ageing was observed. In the study, when the data obtained from WoSCC and Scopus databases and VOSviewer analysis results were evaluated together, a total of 10,170 scientific documents in the Scopus database and a total of 168 scientific documents were identified in the Web of Science database between 1995-2025 worldwide. The author publishing the most on the subject was found to be Cunnane, S.C. The country contributing the most to the field was found to be the United States of America (USA). The institution that produced the most documents was Harvard Medical School. In a total of 10,170 records, the most preferred type of publication was articles. Nutrients journal was the journal with the highest number of publications. According to the results of keyword analysis, the words “ketogenic diet” and “aging” were the most frequently used and most strongly related words.

Conclusion: The results of this study showed a significant increase in the number of studies investigating the effects of KD on ageing. More high-quality, randomised controlled clinical trials are needed in this field. In particular, there is a lack of studies examining the effects of KD on age-related diseases at the molecular level.

Materials and Methods: Three MG patients (male: female = 1:2) and three healthy controls were enrolled for microarray analysis. The “Limma” package was employed to identify the differentially expressed circRNAs (DECs). Target miRNAs of DECs were predicted via the CircInteractome database, while target genes of miRNAs were predicted utilizing miRWalk, miRTarbase, and TargetScan databases. Cytoscape software was applied to establish the circRNAs-miRNAs-mRNAs network. Thereafter, a dual-luciferase reporter assay was conducted to validate the targeted regulatory relationship between hsa_circ_0062400, hsa_circ_0002397, and miR-338-3p. The expression of NRP1 was measured by qRT-PCR and Western blotting, and the cell viability of Jurkat cells was evaluated via CCK-8 assay. The levels of cytokines (IL-2, IL-6, IFN-γ, TNF-α) after NRP1 knockout were detected by ELISA.

Results: 4 circRNAs, 2 miRNAs, and 11 target genes associated with MG pathogenesis were identified to construct a ceRNA regulatory network. In-vitro assays validated the targeted interactions between hsa_circ_0062400, hsa_circ_0002397, and miR-338-3p. miR-338-3p negatively regulated both protein and mRNA levels of NRP1. Further, silencing hsa_circ_0062400 or hsa_circ_ 0002397 markedly suppressed NRP1 expression and Jurkat cell proliferation, which was reversed by miR-338-3p inhibitor. Moreover, NRP1 affected the levels of cytokines in Jurkat cells.

Discussion: The circRNAs were demonstrated to be closely associated with MG etiology, which was also supported by our current discovery that hsa_circ_0062400 and hsa_circ_0002397 regulated the level of NRP1 by sponging miR-338-3p in MG. However, the roles of hsa_circ_0062400 and hsa_circ_0002397 in MG have been rarely reported, which requires further validation. Limitations of this study included a small, gender-imbalanced sample size for microarray analysis and incomplete verification of the ceRNA network. In addition, functional experiments were limited to Jurkat cells, and more in-vivo validation assays were lacking.

Conclusion: Collectively, the present study revealed MG pathogenesis and also provided potential treatment targets for the disease.

Case Presentation: This case report describes a middle-aged female patient diagnosed with LGI1 antibody-associated encephalitis, complicated by Sjögren's syndrome and acute cerebral infarction. The patient presented with an acute onset of symptoms, including delayed response, cognitive impairment, and right-sided weakness. Brain MRI revealed a fresh infarction in the left basal ganglia region. Blood and cerebrospinal fluid tests confirmed the presence of LGI1 antibodies, with blood anti-SS-A antibody levels at +++ and anti-SS-B antibody levels at +, as well as anti- Ro-52 antibody levels at +++.

Conclusions: This report emphasizes the importance of recognizing the overlap between these conditions, as timely diagnosis and intervention can lead to better outcomes in similar cases. By examining the relationship between anti-LGI1 antibody-associated encephalitis, primary Sjögren's syndrome, and acute cerebral infarction, this paper aims to expand the understanding of the complex interactions between autoimmune encephalitis and systemic disorders.

Methods: A systematic literature review was executed across the PubMed and Google Scholar electronic databases spanning the period from January 2000 to December 2024, employing the following keyword combination: “isoliquiritigenin” (MeSH) AND “inflammation” (MeSH).

Results: ISL was found to exhibit significant therapeutic potential in mitigating both acute and chronic inflammatory responses. Particular attention was devoted to elucidating ISL's multi-target regulatory mechanisms in acute organ injury models, including neurological, pulmonary, hepatic, and renal systems. Furthermore, the compound's therapeutic effects were found to extend to chronic inflammatory pathologies associated with metabolic and neurodegenerative disorders, notably diabetes mellitus, obesity-related complications, and Alzheimer's disease-associated tissue damage, particularly manifesting in ocular, pulmonary, and cardiovascular systems. Systematic characterization of ISL's molecular targets and associated signalling cascades, like MAPK, JAK/STAT3, Nrf2, and SIRT1 pathways, substantially enhanced our mechanistic understanding of its anti-inflammatory properties.

Discussion: ISL demonstrated extensive protection in many inflammatory models. Its multi-target action implied broad therapeutic applicability. However, despite its excellent anti-inflammatory efficacy and safety profile, further study is required to investigate its effectiveness for clinical translation.

Conclusion: This comprehensive analysis has provided a pharmacological foundation for developing ISL-based therapeutic interventions against inflammation-driven human pathologies.

Case Presentation: This case presents a seventy-five-year-old woman suffering from colon adenocarcinoma with liver metastasis undergoing pembrolizumab therapy. Shortly after its second administration, she developed severe hypercalcemia (21 mg/dL) with acute kidney failure. Serum intact parathyroid hormone (PTH), parathyroid hormone-related peptide (PTHrP), 25-OH vitamin D, and 1,25-OH vitamin D were suppressed while computerized tomography (CT) imaging ruled out relevant osteolytic or granulomatous lesions. Treatment included hydration, infusion of zoledronic acid, and high-dose glucocorticoids. The patient's serum calcium levels normalized, and her condition improved. Primary hyperparathyroidism, ectopic PTHrP secretion, and ectopic 25(OH) D-1-hydroxylase expression were ruled out by clinical and laboratory data. Notably, experimental models of PD-1/PD-L1 inhibition have demonstrated increased bone resorption. Although the absence of specific bone turnover markers and a recent 18FDG-PET/CT scan partly limits the understanding of the pathophysiological mechanism, immune-mediated osteoclast activation represents a potential pathophysiological mechanism of acute reversible hypercalcemia.

Conclusion: The present case is unique due to its early onset, absence of calcitriol and PTHrP elevation, and rapid response to corticosteroids. Serum calcium should be assessed both before each ICI’s dose administration and throughout treatment in case of symptoms suspicious for hypercalcemia to prevent the onset and progression of this rare but critical irAE.

Methods: A comprehensive literature review was conducted to explore tsRNA biology, radiation- induced cardiovascular injury, and non-coding RNA function. We systematically searched databases including PubMed, Web of Science, and Scopus using keywords such as “tsRNA,” “tRNA- derived fragments,” “radiation-induced heart disease,” “oxidative stress,” and “cardiovascular injury.” Literature screening prioritized original research articles and high-impact reviews providing mechanistic insights into tsRNA expression, biogenesis, or function in the context of radiation response or cardiovascular pathologies. Non-peer-reviewed articles, conference abstracts, non- English publications, or studies not directly relevant to the core themes were excluded. The selected studies were analyzed to identify and synthesize the mechanistic links between tsRNA dysregulation and radiation-induced cardiovascular damage.

Result: Ionizing radiation robustly induces tsRNA biogenesis via endonucleases (e.g., angiogenin, Dicer) in cardiovascular cells. Post-irradiation, specific tsRNAs are dysregulated and contribute to key RIHD mechanisms, including sustained oxidative stress, mitochondrial dysfunction, endothelial senescence, DNA damage response, and fibrotic remodeling. These tsRNAs modulate critical signaling pathways, including PI3K/AKT, JNK, and NF-κB, thereby regulating targets involved in redox balance, apoptosis, and extracellular matrix deposition. Notably, circulating tsRNAs emerge as promising early, non-invasive biomarkers of radiation exposure in both preclinical and clinical settings, highlighting their translational potential.

Discussion: Our study reveals that tsRNAs serve as molecular transducers linking acute radiation stress to chronic cardiovascular dysfunction. Further, they hold promise as early warning biomarkers and therapeutic targets in cardio-oncology.

Conclusion: RIHD is pathologized by tsRNAs. They identify potential non-invasive biomarkers to detect RIHD early and possibly target it for treatment in cancer survivors.

Methods: We conducted a thorough analysis by screening thyroid cancer and paraneoplastic tissues from 20 patients sourced from the Gene Expression Omnibus database. The dataset comprised 11 primary tumor tissues, 6 paraneoplastic tissues, 8 metastatic lymph nodes, and 2 distant metastases of papillary thyroid cancer. Through comprehensive bioinformatic analyses, we constructed a panoramic single-cell atlas of thyroid cancer (THCA).

Results: Our findings revealed significant heterogeneity in gene expression among tumor cells from different patients with THCA, contributing to the development of a comprehensive single- cell landscape. Notably, the long noncoding RNA (lncRNA) gene XIST exhibited higher abundance in anaplastic thyroid cancer (ATC) tumor cells. Additionally, we identified an enriched m6A locus in lncRNA XIST and observed high expression of the m6A “reader” IGF2BP3, as well as low expression of the “encoder” VIRMA. Based on these observations, we hypothesized that IGF2BP3 and VIRMA could augment the expression of lncRNA XIST, thereby promoting the malignant proliferation and invasion of ATC.

Conclusion: By leveraging scRNA-seq technology, our study sheds light on the intricate molecular characteristics of THCA lesions. These findings have the potential to revolutionize our understanding of thyroid cancer pathogenesis and pave the way for innovative therapeutic interventions.

Methods: A young rat model of NAFLD was established by administering a high-fat diet (HFD). Also, Fortunellin was delivered via intragastric administration. The effects of Fortunellin on NAFLD were assessed through hematoxylin-eosin staining, analysis of serum levels of ALT, AST, TCH, TG, LDL-C, and HDL-C, Oil Red O staining, Western blot, ELISA, and quantitative real-time PCR (qRT-PCR). Additionally, the Fortunellin mechanism in NAFLD was estimated with Western blot, immunofluorescence, Oil Red O staining, and ELISA assays.

Results: Functionally, Fortunellin (5 or 10 mg/kg) reduced liver injury in young NAFLD rats, which was mainly associated with the gradual decrease of a liver index, the increased liver tissue score, and the gradually decreased serum levels of ALT and AST. Also, Fortunellin restrained NFALD rat dyslipidemia by lessening TCH, TG, LDL-C serum levels, and increasing HDL-C levels. Furthermore, Fortunellin repressed liver lipid metabolism and immune disorders in young NAFLD rats. Mechanically, Fortunellin enhanced the AMPK activation in young NAFLD rats. Additionally, Fortunellin relieved lipid deposition and immune disorders in young NAFLD rats, while compound C (CC, an AMPK inhibitor) abolished these impacts.

Discussion : This study confirmed that Fortunellin alleviated liver injury in young rats with NAFLD, and this might be achieved by activating the AMPK axis. The completion of this study provided a promising drug for the NAFLD treatment.

Conclusion: In summary, Fortunellin alleviated lipid deposition and immune disorders in young rats with NAFLD through the activation of AMPK.

Objective: This study aims to compare the clinical characteristics, risk factors, and outcomes of CAM and NCM to enhance the understanding and management of these infections, particularly during the COVID-19 pandemic.

Methods: A retrospective multicenter study was conducted at Cukurova University, Malatya İnönü University, and Gaziantep University. We analyzed and compared cases of CAM and NCM diagnosed between January 2018 and February 2022. Data were collected from the infectious diseases and clinical microbiology departments, including demographic details, underlying conditions, treatment regimens, and outcomes.

Results: A total of 38 cases were analyzed, with 21 cases of COVID-19-associated mucormycosis (CAM) and 17 cases of non-COVID-19-associated mucormycosis (NCM). The key findings of the study were as follows: CAM was strongly associated with corticosteroid use (p<0.001) and diabetes (p=0.001), while NCM cases were more frequently linked to malignancy and neutropenia (p<0.05). Clinically, CAM cases had a higher incidence of cavernous sinus involvement and bone destruction (p=0.003) compared to NCM cases. However, there was no significant difference in overall survival between the CAM and NCM groups (p=0.201).

Conclusion: The study highlights the critical role of corticosteroid use and diabetes as prominent risk factors for CAM. Timely diagnosis and intervention are essential to prevent severe complications, such as cavernous sinus involvement and bone destruction. These findings emphasize the need for tailored management strategies for CAM in the context of COVID-19, with particular attention to these risk factors.

Case Presentation: A 19-year-old transgender person assigned female at birth started testosterone therapy to achieve full masculinization. For 14 months, testosterone was administered via transdermal and intramuscular preparations and was well tolerated. However, the individual later developed several angioedematous reactions at different times, despite the use of various testosterone formulations. Allergy evaluations, such as blood tests, SPT, IDT, and drug challenges for both testosterone and excipients, were conducted; the drug challenge for testosterone was positive, confirming it as the trigger of angioedema. The use of omalizumab 150 mg subcutaneously every two weeks allowed the patient to resume testosterone therapy without further systemic reactions. This helped to reduce the patient’s perceived stress and supported his psycho-physical well-being.

Conclusion: Omalizumab was able to successfully manage the systemic allergic reactions to testosterone therapy, and this report could be useful for other clinicians facing similar clinical situations.

Objective: This study aimed to assess the efficacy and safety of SGCs in managing patients with stress-induced hyperglycemia in the intensive care unit.

Methods: A prospective study was conducted involving 22 patients with stress-induced hyperglycemia monitored using the SGCs for 72 hours. Measurements included mean blood glucose, maximum blood glucose, minimum blood glucose, and frequencies of hyperglycemia (> 8.3 mmol/L), hypoglycemia (< 4.4 mmol/L), and target blood glucose (4.4 - 8.3 mmol/L).

Results: Mean blood glucose level was significantly different at 24 hours and 48 hours and 24 hours and 72 hours with SGCs (24h vs 48h, P=0.0289; 24h vs 72h, P=0.0252). The times of hyperglycemia (> 8.3 mmol/L) (24h vs 48h, P=0.0289; 24h vs 72h, P=0.0216) was significantly reduced at 48 hours and 72 hours compared to 24 hours. The average interval between blood glucose measurements was significantly extended at 48 hours and 72 hours compared to 24 hours (24h vs 48h, P=0.0037; 24h vs 72h, P=0.0332). The frequency of target blood glucose (4.4 - 8.3 mmol/L) under SGCs blood glucose management at 48 hours and 72 hours was significantly higher than at 24 hours (24h vs 48h, P=0.0395; 24h vs 72h, P=0.0379). There was no significant difference in the times of hypoglycemia (< 4.4 mmol/L) and the highest blood glucose values between 24 hours, 48 hours, and 72 hours with SGCs glucose management (P>0.05). These findings indicate that SGCs blood glucose management can promote greater stability in the blood glucose levels of patients and alleviate the workload of medical staff to some extent.

Conclusion: SGCs is effective in stabilizing blood glucose levels, increasing the frequency of target blood glucose values, and thereby reducing significant glucose fluctuations, which can improve patient recovery outcomes. Additionally, prolonged use of the SGCs not only optimizes glucose management but also significantly alleviates the workload of nursing staff, enhancing efficiency and allowing for more focused patient care.

Case Presentation: We present the case of a 49-year-old woman with Morris syndrome, diagnosed in 1992, who has undergone gonadectomy and hormone replacement therapy for about 15 years. The patient was referred to our centre for the clinical suspicion of acromegaly in June 2022, for the enlargement of the acral extremities and the development of prognathism in the last 10 years. The patient underwent mandibular reduction surgery and removal of a tubular adenoma of the colon in 2010. In June 2021, the patient performed random GH, IGF-I, and prolactin (PRL) dosages that confirmed the diagnosis of acromegaly. A contrasted pituitary MRI showed the presence of an 8 mm intrasellar pituitary adenoma. Therefore, a transsphenoidal resection of the pituitary tumor was conducted in September 2021. The histological examination proved the diagnosis of somatotropinoma. At the last follow-up at our center in June 2024, the patient presented in a fair general clinical condition, with recovery of related acromegaly symptoms, normalized IGF-I levels, and a negative pituitary MRI for signs of somatotropinoma recurrence.

Conclusion: Our clinical case describes for the first time the association between Morris syndrome and acromegaly. Due to the singularity of this case, we decided to conduct more in-depth genetic analyses through a clinical exome study and CGH Array evaluation, which, however, did not lead to the discovery of a genetic association between the two conditions.

Although this condition is rare, further genetic studies are needed to demonstrate a genetic association between these two conditions.

Methods: A CRISPR-Cas9 genome-wide screening approach was employed to identify key genes involved in cisplatin-induced renal tubular epithelial cell injury. UBE2M, identified as a critical survival factor, was further investigated using both gain- and loss-of-function strategies to explore its biological function and underlying regulatory mechanisms in the Cis-AKI model

Results: CRISPR screening identified UBE2M as a key regulator of cellular survival in Cis-AKI, and subsequent validation experiments confirmed its suppression in cisplatin-induced renal injury models. UBE2M overexpression alleviated apoptosis and renal injury by reducing p53 activation. In contrast, UBE2M knockdown exacerbated these effects, leading to increased apoptosis and renal injury.

Discussion: This study reveals that UBE2M is a critical regulator of cisplatin-induced renal tubular epithelial cell injury. By regulating the p53-mediated apoptotic pathway, UBE2M protects against Cis-AKI.

Conclusion: UBE2M could serve as a novel therapeutic target for the prevention and treatment of cisplatin-induced nephrotoxicity.

Objective: The current study aimed to evaluate the pre-and post-treatment methylation status of ABCG1 and TXNIP loci in individuals diagnosed recently with type 2 diabetes (T2Ds).

Methods: In this quasi-experimental study, individuals recently diagnosed with T2Ds were recruited from 1^st March 2022 to 12^th June, 2023 from diabetes OPDS/clinics. We included the participants (total n=75) as groups that were prescribed Metformin (Met)alone (n=25), Metformin and Dipeptidyl Peptidase- 4 inhibitors in combination (Met+DDP4I) (n=25), and Metformin and Sodium-Glucose co-Transporter 2 Inhibitors in combination (Met+SGLT2I) (n=25). The methylation status of TXNIP and ABCG1 for all the study groups were evaluated by methylation-specific qPCR. Paired T-test and ANOVA were applied to compare the pre-and post-treatment methylation status of the study groups. Pearson’s correlation test followed by multiple linear regression analysis was performed to analyze the respective correlations and effect of different independent variables on the outcome of the study i.e., post-treatment methylation percentages of ABCG1 and TXNIP.

Results: In all groups, post-treatment ABCG1 methylation was found to be significantly decreased, post-treatment TXNIP methylation displayed a significant increase. In a model of linear regression, among various dependent variables, BMI was observed to significantly influence post treatment ABCG1 methylation in all groups, including Met alone (β=0.788, p=0.002), Met+DDP4I, (β= 0.754, p=0.04) and Met+SGLT2I (β= 0.733, p=0.027). While post-treatment TXNIP methylation was significantly affected by reduction in HbA1c levels in all groups, Met alone (β= -0.999, p <0.001), Met+DDP4I (β= -0.850 p <0.001) and Met+SGLT2I (β= -1.007, p <0.001).

Conclusion: Metformin alone and its combinations with DDP4I and SGLT2I decrease the methylation of ABCG1, while increase the methylation of TXNIP in patients with type 2 diabetes. The post-treatment ABCG1 methylation is associated with a decrease in BMI, whereas the post-treatment TXNIP methylation is associated with a decrease in HbA1c levels. Considering the effects of antidiabetic drugs on the methylation status of aforementioned loci involved in the control of glycemic and metabolic parameters; the results of the current study may pave a path for the implementation of precision medicine in type 2 diabetes after further validation by large scale clinical studies.

Objective: We aimed to investigate the role of EphrinB2 in the renal fibrosis model and its underlying mechanisms.

Materials and Methods: Unilateral ureteral obstruction (UUO) models and TGF-β-treated renal tubular epithelial cells (HK2) were adopted in this study to determine if EphrinB2 could lead to renal fibrosis.

Results: EphrinB2 was highly expressed in renal tubular cells in UUO mice. Using adeno-associated virus (AAV)-mediated EphrinB2 overexpression, we observed significant improvements in renal function and injury, as well as a marked reduction in fibrosis. For example, EphrinB2 overexpression decreased the expression of fibrosis markers such as Fibronectin and α-SMA by approximately 40%. In vitro, EphrinB2 also significantly reduced extracellular matrix (ECM) deposition and cellular fibrosis under TGF-β stimulation. Mechanistically, EphrinB2 inhibited TGF-β/Smad3 signaling by approximately 40%, and reduced inflammatory markers such as MCP1 and IL-1β by approximately 60% and 35%, respectively.

Discussion and Conclusion: This study uncovered a previously unrecognized anti-fibrotic role of EphrinB2 in renal fibrosis, which is achieved through the prevention TGF-β/Smad3 signaling and inflammation response. It seemed that EphrinB2 might be a promising therapeutic target in the treatment of fibrotic diseases and kidney failure.

Methods: We utilized summary statistics for 2,888 druggable genes from the eQTLGen Consortium and the FinnGen Consortium for CeD. In our Mendelian Randomization (MR) analysis, we identified genes associated with CeD that had a false discovery rate (FDR) < 0.05 using the Inverse Variance Weighted (IVW) method. To enhance the reliability of the results, we validated them through colocalization analysis and Summary-data-based Mendelian Randomization (SMR) analyses.

Results: Through our analysis, we identified 18 druggable genes with a causal relationship to CeD under an FDR < 0.05. Subsequent colocalization and SMR analyses highlighted the PRKCD gene as a potential therapeutic target for CeD (IVW method: Odds Ratio 1.319, 95% Confidence Interval 1.182-1.471, P = 6.85E-07, FDR = 0.002). Additionally, these results have passed horizontal pleiotropy tests, heterogeneity analysis, and leave-one-out sensitivity analysis.

Discussion: The identification of PRKCD as a therapeutic target represents a significant advancement in addressing the unmet medical need for CeD treatment. However, the hypothesis that PRKCD contributes to CeD pathogenesis by regulating tight junction proteins and altering intestinal barrier function requires further experimental validation in future studies.

Conclusion: Our study is the first to identify the PRKCD gene as a potential therapeutic target for treating CeD, providing new insights into the treatment of CeD and guiding the development of corresponding therapeutic drugs.

Methods: Prospective randomized controlled trials (RCTs) of clomiphene citrate (CC) and letrozole (LE) combined with acupuncture in PCOS infertility patients were identified through computerized searches in databases including PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, and Chongqing VIP Database. The search period was set from inception until August 1, 2023, with no language restrictions. Two researchers screened articles, extracted data, and independently assessed the risk of bias in eligible trials. Data were analyzed and visualized using the R software gemtc package. With patients with medication treatment only set as controls, a meta-analysis was performed to investigate the difference in the pregnancy outcomes of the PCOS patients following medication amalgamated with different acupuncture treatments, namely, manual acupuncture (MA), electroacupuncture (EA), and warm acupuncture (WA).

Results: The serum concentrations of follicle-stimulating hormone (FSH) did not exhibit significant changes following acupuncture treatments. Notably, acupuncture-based medication treatment significantly reduced serum levels of luteinizing hormone (LH) and elevated the testosterone (T) concentrations of patients when compared to medication treatment alone. Patients also showed significantly escalated serum estradiol (E2) levels after receiving CC integrated with acupuncture than those given monotherapy of CC. The combined regimen of medication and acupuncture appeared to improve the pregnancy outcomes compared to the monotherapy of medication, as evidenced by the significantly increased success rate of pregnancy. Furthermore, the treatment combination of CC plus WA and LE plus MA yielded the highest probability of achieving the best pregnancy outcomes.

Conclusion: For PCOS infertility patients, acupuncture, as a complementary treatment to CC and LE, holds advantages in improving reproductive hormone levels and enhancing pregnancy success rates. The highest probability of achieving the best pregnancy outcomes is associated with the treatment combination of CC with WA and LE with MA.

Methods: Active components of CC and their potential antidiabetic targets were identified through TCMSP, DisGeNET, and GeneCards. The PPI networks were constructed with STRING and analyzed with Cytoscape, while GO and KEGG analyses utilized the DAVID database. Molecular docking with core targets was performed using Autodock Vina. The efficacy of CC in diabetes mellitus was evaluated through H&E staining, qPCR, and Western blot in the T2DM mouse.

Results: Eleven active components and sixty-six potential antidiabetic targets of CC were identified. The enrichment analysis revealed 288 GO terms and 37 pathways. The molecular docking showed high affinity for PPAR-γ and IL-6 receptors. In vivo studies further confirmed CC's ability to modulate PPAR-γ and IL-6, contributing to its antidiabetic effects.

Conclusion: CC manages diabetes by regulating the PPAR-γ pathway and suppressing associated inflammation, providing a multi-pathway therapeutic approach.

Objective: The objective of this case-control study was to evaluate the efficacy of empagliflozin in modifying the arterial stiffness in type 2 diabetic patients.

Methods: Pulse wave velocity (PWV) and other parameters of arterial stiffness were assessed at baseline and after three months of empagliflozin treatment in 16 consecutive outpatients with type 2 diabetes mellitus (T2DM) exhibiting normal left ventricular function and no signs of heart failure. A control group of 16 T2DM outpatients not treated with SGLT2 inhibitors was used for comparison.

Results: Duration of diabetes mellitus and sex distribution did not differ between groups. Patients in the empagliflozin group were younger compared to controls (64.1 ± 8.68 vs 74.45 ± 8.13, p < 0.05). At 3-month follow-up, empagliflozin treatment significantly reduced HbA1c (7.9 ± 0.78 vs 7.04 ± 1.09%, p < 0.008). Empagliflozin significantly improved PWV compared to controls (from 13.2 ± 2.0 m/sec to 12.3 ± 1.8 m/sec; P = 0.001; in the control group 12.8 ± 2.3m/s to 13.2 ± 2.4, p = ns, with age and HbA1c as covariates) as well as body weight that significantly reduced (86.75 ± 16.16 kg vs 81.71 ± 16.5 kg, p =0.001) and BMI (30.48 ± 5.4 versus 28.75 ± 5.66 kg/m2, p < 0.002) in comparison to controls. Estimated glomerular filtration rate (eGFR) remained unchanged whereas a significant improvement of urine Albumin to Creatinine ratio with empagliflozin emerged (17.8 ± 46.8 vs 12.2 ± 35.7 mg/mmol, p = 0.049).

Conclusion: In this clinical study, mid-term treatment with empagliflozin in patients with type 2 diabetes mellitus (T2DM) resulted in a significant reduction in arterial stiffness. Additionally, the improvement in the urine albumin-to-creatinine ratio suggests a potential enhancement in endothelial function.

Methods: Paraffin-embedded tissue blocks from PTC patients (n=255) who underwent thyroid surgery between 2020 and 2021 were analyzed for EBV and HPV DNA using PCR-based methods.

Results: Results showed EBV positivity in 45.1% of PTC cases, significantly higher than in benign thyroid tumors (35.2%), while HPV positivity was low (0.7%). EBV positivity was not associated with age, gender, lesion type, lymph node metastasis, or extrathyroidal extension but was significantly higher in PTC cases with concurrent Hashimoto's thyroiditis. The study suggests a notable presence of EBV in PTC, especially in cases with Hashimoto's thyroiditis, but indicates a limited role for HPV in thyroid cancer.

Conclusion: Further research is warranted to understand the specific pathogenic mechanisms and potential therapeutic implications of EBV and HPV in thyroid cancer.

Case Presentation: A 63-year-old Caucasian male known for right adrenal pheochromocytoma waiting for surgical removal was admitted to the Emergency Department (ED) in March 2021 for a fainting episode and hypertensive crisis that he never experienced before.

The patient had a known medical history of type 2 mellitus diabetes and hypercholesterolemia treated by slow-release metformin 500 mg/day and atorvastatin 40 mg/day and was not vaccinated for Sars-CoV-2. Two months before, the patient was hospitalized in another hospital for myocardial infarction with non-obstructive coronary arteries, and a chest-abdomen TC scan showed a right adrenal lodge occupied by coarse formation. In the 24-h urine sample, metanephrines were >5000 μg/24 h and Normetanephrines >2500 μg/24 h. Scintigraphy with 123I-Metaiodobenzylguanidine (MIBG) showed accumulation in right adrenal gland formation, confirming the suspicion of pheochromocytoma. No further areas of pathological uptake were present. Fort that, the patient was started on alpha-blockers (doxazosin 2 mg twice/day). Two weeks later, the patient was also prescribed metoprolol 50 mg twice/day.

When admitted to the Emergency Department (ED), Blood Pressure (BP) was 210/108 mmHg with a heart rate of 105 bpm. A routine nasopharyngeal swab for Sars-CoV-2 was performed, resulting positive. After an extra dosage of 2 mg of doxazosin and 20 mg of nifedipine, symptoms addressed to catecholamine release disappeared. Being positive for Sars-CoV-19, the patient was transferred to the infectious diseases department. High mean BP was demonstrated at the control profile. Doxazosin was increased to 4 mg twice a day with a good effect on BP and tachycardia. After 10 days, the SARS-CoV-2 swab result was negative, and the patient was discharged with normal vital parameters and instructions to continue the increased dose of doxazosin. No other crisis was reported until surgery, which was performed without any complications after 1 month.

Conclusion: Since the adrenal crisis is a life-threatening condition, we suggest close BP monitoring and therapeutic adherence in patients with pheochromocytoma waiting for surgery and living in areas characterized by outbreaks of COVID-19 infection. Moreover, we suggest considering an increase in alpha-blocker dosage to prevent the crisis.

Methods: We recruited a total of 135 subjects from the outpatient department of the ENT unit of our institute. Real-time Polymerase Chain Reaction (PCR) was used to evaluate the levels of TAP-1 and TAP-2 gene expression in pre-cancerous and oral squamous carcinoma samples. Additionally, we measured the circulating levels of inflammatory markers using an automated biochemistry analyzer.

Results: In the current study, we found that the subjects with oral squamous cell carcinoma had lower expressions of the TAP 1 and TAP 2 genes than precancerous oral subjects of OSMF, leukoplakia, and OLP. In oral squamous carcinoma subjects, we found a 1.7- and 2.1-fold change in gene expression of TAP-1 and TAP-2, respectively, compared to control subjects. Furthermore, we observed an increased levels of metabolic inflammatory biomarkers, including CRP, ESR, and ferritin in oral squamous carcinoma subjects compared to premalignant cases and controls, indicating the presence and aggravation of systemic inflammation.

Conclusion: The study revealed that subjects with oral squamous cell carcinoma have lower TAP 1 and TAP 2 gene expression than premalignant control subjects, thus affecting MHC-I processing, which ultimately affects the functioning of the immune system. These results have the potential to improve our understanding of disease pathophysiology and provide more targeted treatment options.

Objective: We aimed to explore the role and mechanism of PF4 on trophoblasts in RM in vitro.

Methods: In this study, the expression of PF4 and PF4 receptor CXC chemokine receptor 3 (CXCR3) in the placentas of patients with RM were analyzed by RT-qPCR and western blotting. Serum PF4 level was tested by ELISA. Following PF4 silencing and SOCS3 overexpression in HTR-8/SVneo cells, cell proliferation was detected by CCK-8, colony formation, and EDU assays. Wound healing and transwell assays separately evaluated cell migration and invasion. Immunofluorescence assay determined E-cadherin expression. Tube formation assay was used to measure the angiogenesis. Western blotting examined the expression of metastasis, epithelial-mesenchymal transition (EMT) and suppressor of cytokine signaling 3 (SOCS3)/signal transducer and activator of transcription 3 (STAT3) signaling-associated proteins.

Results: The results revealed that PF4 displayed increased expression in placental villus tissues of RM patients. Serum PF4 level was also elevated in RM patients. PF4 silencing promoted the proliferation, migration, invasion, EMT, and angiogenesis of HTR-8/SVneo cells. Additionally, PF4 knockdown downregulated SOCS3 expression to activate STAT3 signaling. SOCS3 overexpression countervailed the effects of PF4 deficiency on HTR-8/SVneo cells.

Conclusion: In summary, PF4 participated in the proliferation, migration, invasion, EMT and angiogenesis of trophoblast cells by modulating the SOCS3/STAT3 signaling pathway, indicating that targeting the PF4/SOCS3/STAT3 pathway could be a novel therapy for RM.

Objective: This study aimed to explore the effects of amino acid supplementation in conjunction with a standard psycho-nutritional rehabilitation program on body composition, symptoms and psychopathology status in 30 female patients with eating disorders hospitalized at the Residenza Palazzo Francisci in Todi, Italy.

Methods: Enrolled patients were divided in two groups receiving amino acid supplementation for 45 and 90 days, respectively. Each patient underwent bioelectrical impedance analysis at baseline, after 45 days and after 90 days. Validated psychometric tests were administered at study entry and study end to all enrolled patients.

Results: Results from bioelectrical impedance analysis suggest that amino acid supplementation contributes to restoring nutritional and metabolic balance, with effects proportional to the duration of administration. Conversely, interpreting the effects on psychopathologic state and symptoms was challenging, probably due to the small sample size and short observation period.

Conclusion: Prolonged amino acid supplementation may play a role in the management of patients with eating disorders, favoring the correction of the catabolic state and possibly contributing to improvement of the psychopathologic state.

Methods: A retrospective cohort study using data from the UK Biobank (UKB) and a cross-sectional analysis from the National Inpatient Sample (NIS) were conducted. Propensity score matching was applied to control for confounding factors. Cox proportional hazards models (UKB) and logistic regression models (NIS) were used to evaluate the association between IBS and hypothyroidism. Subgroup analyses by age and sex were performed.

Results: The UKB cohort included 22,970 IBS patients (mean age 56.1 ± 7.94 years, 72.2% female) with a hypothyroidism prevalence of 4.1%, compared to 438,094 non-IBS participants (mean age 56.4 ± 8.12 years, 51.9% female) with a prevalence of 2.9%. In the NIS, 183,738 IBS patients had a hypothyroidism prevalence of 20.6%, compared to 10.3% in 20,298,589 non-IBS participants. After PSM, the hazard ratio (HR) for hypothyroidism in IBS patients was 1.21 (95% CI: 1.12–1.30, P < 0.001) in the UKB, and the odds ratio (OR) was 1.25 (95% CI: 1.23–1.27, P < 0.001) in the NIS. Subgroup analyses showed a higher risk for hypothyroidism in IBS patients, particularly those aged ≤65 years and females.

Conclusions: IBS is associated with an increased risk of hypothyroidism. Clinicians should consider screening for thyroid dysfunction in IBS patients to improve patient outcomes.

Methods: To identify differentially expressed genes (DEGs) associated with immune dysfunction and mitochondrial pathways in PAAD, data from TCGA, GTEx, and three GEO datasets were integrated. Differential gene expression was analyzed using DESeq2, applying criteria of p-value < 0.05 and |log₂ fold change| > 1. Using the “immune dictionary” framework, a prognostic model was developed through LASSO-Cox regression, followed by survival analysis for validation. The expression of key genes identified in the bioinformatics analysis was validated by quantitative real- time PCR (qPCR) on paired PAAD tissue and adjacent normal samples, focusing on NOG, TNFSF9, and TNFSF10.

Results: Fifty-two DEGs associated with immune and mitochondrial dysfunction were identified. Gene set enrichment analysis revealed critical pathways, including IL-4 signaling, NF-κB activation, and autophagy. The LASSO-Cox model identified 12 prognostic genes that effectively stratified patients into high- and low-risk groups with high predictive accuracy. Validation confirmed significant differential expression patterns, consistent with computational findings.

Discussion: This study, utilizing the immune dictionary framework, systematically analyzed immune- related and mitochondria-related genes in PAAD, identifying 12 DEGs for prognostic modeling. It revealed significant correlations between immune evasion and mitochondrial dysfunction, offering novel targets for personalized therapy.

Conclusion: This study presents an innovative immune dictionary approach to identify key immune- and mitochondria-related DEGs in PAAD, providing potential targets for new therapeutic strategies and personalized treatment approaches.

Objective: This systematic review and meta-analysis aimed to determine the effect of the GCKR polymorphisms on GDM susceptibility.

Methods: Seven literature databases were searched (from inception to February 17, 2024) to locate relevant studies included in further meta-analysis. Odds ratio (OR) and 95% confidence intervals (CI) in the pooled population were estimated to assess the effects of the variant allele on GDM risk.

Results: For the rs780094 polymorphism, 13 datasets with 3443 GDM cases and 5930 nondiabetic controls were included. The pooled estimates in the allele model (OR: 1.19, 95% CI: 1.07~1.32), homozygote model (OR: 1.27, 95% CI: 1.10~1.47), dominant model (OR: 1.16, 95% CI: 1.03~1.31), and recessive model (OR: 1.31, 95% CI: 1.09~1.57) suggested that the C allele carriers were prone to GDM. For the rs1260326 polymorphism, five datasets with 1495 cases and 2678 controls were integrated. The statistically significant effect of the C allele was evident in the allele model (OR: 1.12, 95% CI: 1.01~1.24) and the homozygote model (OR: 1.26, 95% CI: 1.03~1.54).

Conclusion: This meta-analysis suggested that the C allele of the rs780094 and rs1260326 polymorphisms in the GCKR gene are significantly associated with increased risk of GDM.

Methods: Sixty-eight participants were recruited for the discovery experiment (NOGD: healthy control (HC) = 39:29). Peripheral Blood Mononuclear Cells (PBMCs) were isolated. Flow cytometry was performed to detect CD226 expression on multiple lymphocyte subtypes. CD226 mRNA expression in PBMCs was detected by qPCR. Fifty-eight participants were recruited for the validation experiment (NOGD: HC=35:23). CD4⁺ T cells were isolated, and the level of CD226 mRNA in CD4⁺ T cells was detected. Five cases of each of Graves' disease (GD) thyroid and control thyroid were collected for CD226 immunohistochemical staining.

Results: CD226 expression was the highest in monocytes (NOGD: 94.1% vs. HC: 94.8%) and the lowest in CD8⁺ T cells (NOGD: 65.3% vs. HC: 64.9%). Compared with HC, CD226 expression on the CD4⁺ T cells increased in the peripheral blood of NOGD patients and correlated with TPOAb. Meanwhile, CD226 mRNA levels were elevated in CD4⁺ T cells and positively correlated with TR-Ab. CD226 expression was significantly increased in the thyroid tissues of GD patients.

Conclusion: This study demonstrates for the first time the elevated expression of CD226 in CD4⁺ T cells and thyroid tissue of NOGD. The abnormal elevation of CD226 is correlated with clinical indicators. It suggests that the co-stimulatory molecule CD226 is involved in the pathogenesis of GD.

Methods: This randomized trial was conducted over 180 days in 58 patients with T2DM and HF, assigned in a 1:1 ratio to standard therapy or standard therapy plus dapagliflozin 10 mg daily. Lipid, glycemic, and IR parameters were assessed at baseline, 12 weeks, and 24 weeks.

Results: Dapagliflozin group showed marked improvements in BMI (p = 0.01), TC (p = 0.02), TG (p = 0.01), HDL (p = 0.001), LDL (p = 0.002), and VLDL (p = 0.01), FPG (p = 0.0001), PPG (p = 0.002) and HbA1c (p = 0.01), HOMA-IR (p = 0.002), HOMA2%B (p = 0.003), and decreased insulin levels (p = 0.001) by 24 weeks. In contrast, significant changes were noted only in LDL (p = 0.01), HDL (p = 0.03), and TG (p = 0.01) in the standard group. A positive correlation was observed between the mean change in TG and HOMA-IR after 24 weeks of dapagliflozin treatment.

Discussion: Dapagliflozin improved lipid profile and reduced IR, demonstrating benefits in T2DM and HF patients, which aligned with the findings from the larger SGLT2i trials. Study limitations included the small sample size, single-center setting, and an open-label design.

Conclusion: Dapagliflozin improved lipid and IR, highlighting its potential as an adjunctive therapy in patients with co-morbid T2DM and HF.

Clinical Trial Number: CTRI/2024/01/06208

Methods: Sixty 8-week-old NOD.H-2h4 mice of SPF grade were selected and randomly divided into six groups: control group, model group, Buzhong Yiqi decoction low, middle, and high-dose groups (4.78, 9.56, 19.12 g·kg^-1), and Western medicine group (selenium yeast tablets, 3.033×10^-5 g·kg^-1), with ten mice in each group. All groups of AIT model mice were allowed to drink a 0.05% sodium iodide solution freely for 8 weeks to establish the AIT model, while the control group drank distilled water freely. ELISA, HE staining, Real-time PCR, and Western Blot were used to assess serum antibodies, thyroid pathology, and expression levels of Wnt5a, β-catenin, PPAR, GSK-3β, IL-1β, and IL-6.

Results: The model group showed increased TgAb and TPOAb levels (P<0.01), lymphocyte infiltration, and altered expression of Wnt5a, β-catenin, PPAR, GSK-3β, IL-1β, and IL-6 (P<0.01). Buzhong Yiqi decoction groups and Western medicine groups significantly reduced these effects, indicating improved thyroid function and inflammation reduction.

Discussion: Buzhong Yiqi decoction modulates the Wnt5a/β-catenin pathway, suggesting a potential therapeutic approach for AIT by reducing inflammation and restoring thyroid function.

Conclusion: Buzhong Yiqi decoction can effectively improve AIT inflammatory damage, and the modulation of the Wnt/β-catenin signaling pathway may be one of its intervention mechanisms.

Materials and Methods: We obtained the expression profile chip data GSE197884 from the Gene Expression Omnibus (GEO) database. Subsequently, “DESeq” and “Limma” R packages were employed to identify differentially expressed genes (DEGs) while constructing a co-expressed gene network using weighted gene co-expression analysis (WGCNA). Functional enrichment analyses were then carried out, followed by the construction of a protein-protein interaction (PPI) network to uncover core genes. The core genes were confirmed through data retrieved from The Cancer Genome Atlas (TCGA) database in order to determine their status as hub genes. Finally, survival and tumor immune infiltration analyses were performed to unveil the prognostic significance of these hub genes.

Results: In total, 126 intersection targets were retrieved through the Venn diagram. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses revealed that the DEGs were primarily related to the proliferation and apoptosis of HCC cells, the digestion and metabolism of liver cells, the HCC tumor microenvironment, and immune response. The PPI network analysis identified 11 core targets, among which seven hub genes, including NSDHL, MVK, SQLW, GCAT, ALAS2, GLDC, and AGXT, were obtained after TCGA database validation. Furthermore, it was found that NSDHL was closely associated with the clinical diagnosis and prognosis of HCC induced by HFD/SW and also affected the cellular immune infiltration in the HCC tumor microenvironment.

Conclusion: The present study demonstrated a significantly elevated expression of NSDHL in HCC tissues, suggesting its potential as a specific biomarker for precise clinical diagnosis and prognosis assessment of HCC induced by HFD/SW.

Case Presentation: We report a septic patient with pseudo-Cushing's syndrome in the pre-agonal phase, suggesting that PCS during sepsis is an underestimated condition, as the severity of the patient's clinical condition is compounded by the difficulty of diagnosis itself.

Conclusion: In this clinical case, for the severe clinical conditions of the patient and the poor prognosis, we conducted a comprehensive endocrine work-up to rule out an ACTH-dependent hypercortisolism that, if confirmed, could have changed the therapeutic approach and the prognosis of the reported patient.

Methods: The Web of Science database was selected as the source of literature, and all the literature on MSCs in diabetes from January 1, 2000, to October 18, 2023, was selected. After screening, CiteSpace and VOSviewer were imported into bibliometric software to construct the knowledge visualization map. Journal analysis, author analysis, country/region analysis, reference analysis, and keyword analysis were performed.

Results: A total of 2912 articles and reviews were included. The number of articles on the use of MSCs for the treatment of diabetes is increasing annually. These publications originate mainly from 90 countries and 278 institutions, of which China and the United States were the top producers. We identified 15384 authors, with Liu Jiejie having the largest number of articles and Shapiro Amj being the most frequently co-cited. Stem Cell Research and Therapy was the most studied journal, and Diabetes was the most frequently cited journal. After analysis, the most common keywords were MSCs, diabetes mellitus, expression, transplantation, and differentiation.

Conclusion: Research into MSC-based interventions for diabetes is booming. In the future, cooperation and connections between various countries and institutions should be strengthened. MSC-induced differentiation into insulin-producing cells, MSCs homing in vivo, the therapeutic effect of MSCs on diabetic nephropathy, and the therapeutic effect of exosomes secreted by MSCs constitute the current research hotspots and development trends for future research.

Methods: 24 PA patients and 24 healthy adults served as the control group in this study. Six participants were chosen from each group to have their peripheral blood and serum samples analyzed for omics investigations. Another eighteen participants' peripheral blood samples were selected for further validation of the RNA-sequencing results.

Results: Transcriptomic analyses found 518 differentially expressed genes (DEGs), and 339 remarkably differential metabolites (DMs) were identified by untargeted metabolomics. The pathway enrichment analysis was performed by combining with the omics analysis data. We also focused on analyzing metabolic pathways that repeatedly occur and constructed possible genemetabolic networks. A total of 5 genes and 11 metabolites showed significant changes in altered 3 lipid metabolic pathways. Furthermore, the expressions of these genes were verified by qRT-PCR.

Conclusion: The combination of metabolomic and transcriptomic data can give a comprehensive picture of unique illness markers and preliminary knowledge of the molecular abnormalities underpinning PA. These findings may point to viable targets for creating treatments.

Methods: In a cross-sectional study at a tertiary healthcare facility's endocrinology and metabolism outpatient clinic, participants who had undergone their first thyroid FNAB and attended the clinic to review their results were included. Data collection encompassed demographic information, clinical history, and sonographic features of thyroid nodules. Patient knowledge was assessed using a 6-item questionnaire that evaluated awareness of the indications for thyroid FNAB, potential diagnostic outcomes, and the likelihood of a repeat biopsy.

Results: A total of 423 patients participated in this study, with the majority being female (83.7%). The median age was 54 years. The indication for the biopsy was correctly identified by 68.5% of participants. Awareness of the potential for benign (85.1%) and malignant (84.6%) results was high. However, only 20.4% were informed about non-diagnostic outcomes and 16.6% about indeterminate results. Furthermore, 34.1% understood the need for a repeat biopsy. Participants under 65 years of age demonstrated significantly higher knowledge regarding the reason for the biopsy and the potential for benign or malignant results (p < 0.001). Participants with at least a high school education (38.1%) were more knowledgeable about all aspects of FNAB compared to those with lower educational levels (p < 0.05). Patients with a history of non-thyroidal malignancy (5.7%) demonstrated significantly greater understanding of non-diagnostic and indeterminate results (p < 0.001).

Conclusion: The study reveals substantial knowledge gaps, particularly in understanding thyroid FNAB and its outcomes. Thus, targeted educational interventions are necessary to enhance patient comprehension and improve clinical outcomes.

Methods: A hospital-based cross-sectional study of 100 women aged 20–40 years was conducted at the University of Lahore Teaching Hospital from December 2023 to September 2024. Participants were stratified according to normal weight (BMI < 25 kg/m²) and elevated BMI (BMI ≥ 25 kg/m2) groups with healthy and PCOS as subgroups within each group.

Results: The left ovarian volume in PCOS patients was significantly larger than that in women without PCOS (mean 13.5 mL (SD 3.6) vs 10.4 mL (SD 1.9), P < 0.05). Likewise, the mean follicle size in the left ovary was also significantly larger in women with PCOS than in normal controls, 6.3 mm (SD 1.7) and 5.6 mm (SD 1.1), respectively (P < 0.05). PCOS showed a significant association with amenorrhea (85%) and acne (66%); however, 59% of participants showed hirsutism which was not significant.

Discussion: The observed asymmetry in ovarian volume and the influence of BMI suggest underlying physiological variability. However, the absence of hormonal and metabolic data limits the interpretation, warranting cautious application of these findings.

Conclusion: Ovarian volume alone is not a reliable diagnostic marker for PCOS. While the left ovary showed significant differences, the inconsistent findings support the need for a combined clinical, biochemical, and sonographic approach.

Materials and Methods: HDAC scores were computed by ssGSEA. WGCNA was applied to identify HDAC-related gene modules, followed by functional enrichment analysis. Machine learning methods were employed to screen diagnostic biomarkers. Immune infiltration analysis and molecular docking were performed to validate gene-immune correlations and potential drugs. An in-vitro sepsis model was established by using lipopolysaccharide to induce THP-1-derived macrophages. The gene expression and inflammatory factor levels were assessed using qPCR, Western blot, and ELISA methods. Finally, the effect of TRIM24 knockdown on cell apoptosis and inflammatory responses was analyzed.

Results: Two HDAC-related genes (TOM1L2, TRIM24) were identified as potential diagnostic biomarkers for sepsis, showing significant correlation with immune cell infiltration. Molecular docking confirmed the binding capacity of Acetaminophen, 8-azaguanine, and Ochratoxin A with the two biomarkers. In-vitro sepsis model showed that TRIM24 knockdown markedly lowered the levels of pro-inflammatory cytokines and apoptosis.

Discussion: The two biomarkers, along with the RiskScore model, could potentially contribute to the prognostic assessment of sepsis and the development of personalized treatment. However, further experimental validation is also needed to substantiate our findings and to translate them into practical clinical applications.

Conclusion: This study identified TOM1L2 and TRIM24 as key HDAC-related biomarkers for sepsis, providing novel insights for the early diagnosis and targeted treatments of sepsis.

Methods: Data were collected from Gene Expression Omnibus (GEO). Enrichment scores were calculated by single-sample gene set enrichment analysis (GSEA), while pathway analysis was performed using GSEA. Key modules were identified through weighted gene co-expression network analysis (WGCNA), followed by the screening of differentially expressed genes (DEGs) using the limma package. The intersection genes were further screened by LASSO and Support Vector Machine-Recursive Feature Elimination (SVM-RFE). Potential transcription factors (TFs) were predicted using hTFtarget, and related microRNAs were analyzed using the Encori database. The TF regulatory network was visualized using Cytoscape 3.8.0.

Results: Patients with cryptorchidism exhibited significantly higher early estrogen response scores compared to controls, with a notable enrichment of the early estrogen response pathway. This study identified 2 biomarkers, PRR15 and SRPX, which were both regulated by the TF SPI1. PRR15 gene expression was significantly related to early estrogen response. Additionally, these two biomarkers were primarily involved in cell division pathways; in particular, PRR15 was closely linked to progesterone-mediated oocyte maturation.

Discussion: PRR15 and SRPX, which SPI1 potentially regulated, were identified as genes associated with early estrogen response in cryptorchidism and were enriched in estrogen-related and cell division pathways.

Conclusion: This study provided translational insights, enhancing the current understanding of testicular pathogenesis and contributing to the diagnosis and treatment of cryptorchidism.

Methods: Data mining of CP literature for UC from VIP, CNKI, WanFang, and PubMed (2013–2023), which focused on herb usage frequency, properties, flavors, meridian tropisms, core herb pairs, and UC categories. Finally, the top ten CPs were further analyzed for clinical application.

Results: A total of 62 prescriptions from 383 articles were analyzed, and the most frequently used prescriptions were Sishen pill, Huangqin decoction, and Shaoyao decoction. The greatest frequency herbs were Glycyrrhizae Radix et Rhizoma, Coptidis Rhizoma, Paeoniae Radix Alba, and Atractylodis Macrocephalae Rhizoma. Herbs were pungent, bitter, and sweet in flavor with properties mainly being warm, cold, and neutral and targeting the liver, spleen, stomach, and heart meridians. Core herb pairs included Bupleuri-Poria, Atractylodis-Saposhnikoviae, Zingiberis-Jujubae, Phellodendri Chinensis Cortex -Coptidis Rhizoma, Pinelliae Rhizoma-Ginseng Radix et Rhizoma. Through cluster analysis, the herbs were categorized into four distinct clusters. Furthermore, the CP primarily exerted therapeutic effects by alleviating inflammation, restoring mucosal barriers, and maintaining immune balance.

Conclusion: Data mining identified Sishen Pill, Huangqin Decoction, and Shaoyao Decoction as the top three CPs for UC. The main mechanism of treating UC is by reducing inflammation, maintaining immune balance, and repairing the mucosal barrier.

Methods: The Gene Expression Omnibus (GEO) was utilized to get microarray data. Differentially expressed genes (DEGs) in individuals with CD and RA were identified. Weighted gene co-expression network analysis (WGCNA) was used to identify key modular genes in CD and RA. The least absolute shrinkage and selection operator (LASSO) logistic regression was used to identify hub genes. The correlation between immune cell infiltration and common biomarkers was examined by utilizing the GSEA and ssGSEA.

Results: CD27 and GZMK were recognized as co-biomarkers in RA and CD. The analysis of immune infiltration revealed a significant relationship between a range of immune cells, including CD8 T cell, MDSC, and natural killer T cell, and both RA and CD.

Conclusion: CD27 and GZMK are biomarkers shared by CD and RA and are potential diagnostic and therapeutic targets for them, especially in patients with CD combined with RA. CD and RA are highly associated with dysregulation of the acquired immune response system and imbalance of the innate immune system.

Objective: This study aimed to evaluate the effectiveness of medication adherence education interventions for the clinical outcomes of adults with T2DM.

Materials and Methods: Seventy adults with T2DM from an outpatient clinic in the City of Ardabil, Iran, participated in this study. The participants were randomized into an intervention group (n=35) or a non-interventional group (n=35). The intervention group underwent four educational sessions focused on adherence to OADs. Content within classes was influenced by a participant’s Stage of Change (SOC) result, which was related to behavior change modeling. Participants in the non-interventional group were placed on a waiting list to receive educational content after the follow- up. Assessments were conducted at baseline, four weeks, and six months.

Results: Significant improvements in Fasting Plasma Glucose (FPG) (P = 0.018) and 2-hour Plasma Glucose (2-hPG) (P < 0.001) levels were found in the intervention group compared to the noninterventional group post-intervention. Additionally, HbA1C was significantly lower at follow-up in the intervention group than in the non-intervention group (P < 0.001). The Homeostasis Model of Insulin Resistance Assessment (HOMA-IR) revealed a significant increase in target cell sensitivity to insulin in the intervention group compared to that in the non-interventional during the follow- up period (P = 0.009). The SOC for adherence to OADs was significantly improved in the intervention group compared to that in the non-intervention group at the follow-up timepoint (P< 0.001).

Conclusion: Medication adherence education interventions may improve the clinical outcomes of adults with T2DM.

Clinical Trial Registration Number: IRCT201701165670N23.

Methods: The research integrated multi-dimensional research methods, including network pharmacology, metabolomics, and animal experiments, to comprehensively investigate the scientific mechanisms of Gushukang granules' intervention in sarcopenia.

Results: Network pharmacology analysis identified multiple potential targets related to muscle growth and repair. UPLC-Q-TOF MS technology tracked metabolic pathways, while animal experiments verified that Gushukang granules precisely regulate muscle metabolic balance by modulating key signaling pathways involved in protein synthesis and degradation.

Discussion: The findings demonstrate the potential of integrating traditional and modern medical approaches in addressing age-related muscle degradation, providing scientific validation for TCM treatment of sarcopenia.

Conclusion: This study establishes a model for modernizing TCM research, offering solid scientific evidence for comprehensive intervention of chronic diseases in the elderly and highlighting the TCM concept of “preventing disease before its onset” in modern medical translation.

Materials and Methods: Single-cell data were preprocessed using the Seurat package. The communication network between cell subpopulations and fibroblasts was analyzed using CellChat. Key hub genes were initially identified through hdWGCNA, while differentially expressed genes (DEGs) between cancer and control groups were obtained using DESeq2. Subsequently, the overlapping genes between the hub genes and DEGs were subjected to LASSO regression (via the glmnet package) and SVM-RFE (implemented in e1071 package) to select biomarkers for GC. Immune cell infiltration was assessed using the CIBERSORT package, and functional enrichment analysis was performed on the background gene set by GSEA_4.2.2 software. Finally, drugs targeting the biomarkers were predicted by employing the DSigDB database.

Results: Single-cell analysis identified eight major cell subpopulations, with fibroblasts distinctly marked by DCN and LUM expression. Cell communication analysis revealed that HLA-ECD94: NKG2A and HLA-E-KLRC1 were the main interactions through which other cell clusters exerted influence on fibroblasts. COL1A1 and SERPINH1 were identified as CAF-related biomarkers that promoted GC progression through macrophage-mediated immune infiltration. High co-expression of the two genes was significantly enriched in epithelial-mesenchymal transition (EMT).

Discussion: COL1A1 and SERPINH1 may promote GC progression via regulating EMT and forming an immunosuppressive microenvironment through ECM remodeling and macrophage polarization. Additionally, chitosamine was screened as a potential COL1A1-targeting drug for GC treatment.

Conclusion: These findings have deepened our current understanding of CAF-mediated mechanisms in GC, contributing to the development of precision diagnostics and therapeutics in GC.

Methods: Blood samples drawn for thyroid parameters in each trimester during the antenatal period were determined after the participants gave birth. Serum thyrotropin, free thyroxine, free triiodothyronine, anti-thyroid peroxidase antibody (TPOAb), and anti-thyroglobulin antibody (TgAb) levels were tested using electrochemiluminescence immunoassays.

Results: Among all the participants, TAI and hypothyroxinemia in the first trimester (T1) were significantly related to an increased risk of gestational hypertension (OR=5.136, 95% CI 1.537-17.158 and OR=7.683, 95% CI: 1.890-31.229, respectively). Additionally, subclinical hypothyroidism in T1 was independently associated with a higher risk of postpartum hemorrhage (OR = 38.063, 95% CI 2.091-692.834). Besides, subclinical thyrotoxicosis in T1 showed a significant correlation with a raised risk of small for gestational age (OR=14.650, 95% CI 1.221-175.760). Among euthyroid women during the whole pregnancy, either TPOAb+ or TgAb+ in the third trimester was an independent risk factor of premature birth (OR=5.092, 95% CI 1.059-24.481) and low birth weight (OR=8.165, 95% CI 1.717-38.824), respectively.

Conclusion: Our findings indicate the importance of screening thyroid parameters in early pregnancy and the need to dynamically monitor these parameters throughout the entire pregnancy.

Methods: The db/db mice were gavaged with 25 mg/kg, 50 mg/kg, and 100 mg/kg of 1-DNJ for 8 weeks. At the end of the administration, the serum and liver were isolated for further detection. The biochemical indices including TC, TG, LDL-C, AST, ALT, and TBiL were detected in serum. The livers were further analyzed with H&E, oil red, and Masson staining, and the amount of ROS in the liver was detected with probe dihydroethidium. Western blot was used to analyze the levels of proteins involved in fibrosis, oxidative stress, and AMPK/SIRT1 signaling pathway in the liver.

Results: 1-DNJ administration reduced body weight, liver coefficient, and TC, TG, LDL-C, AST, ALT, and TBiL in db/db mice. H&E and oil red staining showed that 1-DNJ ameliorated hepatocellular ballooning degeneration and lipid deposition in the liver. Moreover, 1-DNJ reduced the hepatic collagen fiber deposition and the protein expression of α-SMA and Collagen I. Further assays revealed that 1-DNJ treatment reduced the ROS level, up-regulated the proteins expression of SOD2, HO-1, NQO-1, p-AMPK/AMPK, p-ACC/ACC, and SIRT1 proteins, and down-regulated the expression of SREBP-1 and SCD-1 proteins in the liver.

Conclusion: 1-DNJ improves liver function, lipid deposition, and fibrosis of diabetic liver injury in db/db mice by regulating the AMPK/SIRT1 pathway to improve glucose-lipid metabolism and oxidative stress.

Methods: A retrospective analysis was conducted over a ten-year period, reviewing the clinical and surgical records of patients diagnosed with Hirschsprung disease. Pathological sections were re-evaluated, and patient medical histories, prior surgeries, and other relevant clinical data were confirmed.

Results: A total of 106 cases of Hirschsprung disease were identified. The mean age at diagnosis was 2.4 ± 3.0 years, with 40.6% of cases diagnosed within the first year of life. The male-to-female ratio was 2.6:1. The most commonly affected anatomical sites were the colon (35.8%) and rectum (23.6%). Pathological evaluation revealed the absence of ganglion cells in 57.5% of cases. Rectal biopsy was the most frequently performed diagnostic procedure (64.2%), and colon resection was required in 35.8% of cases. A significant association was found between disease presence and anatomical site involvement (P = 0.010) and surgical intervention (P = 0.046).

Conclusion: The study highlights a male predominance in Hirschsprung disease, with the majority of cases diagnosed within the first year of life. The rectum and colon were the most commonly affected sites. Significant associations were observed between disease presence and anatomical site involvement, as well as surgical interventions, emphasizing the importance of early diagnosis and appropriate management strategies.

Objective: The core objective of this review is to elucidate the pathogenesis, clinical risk factors, and significance of different types of herbal medications utilized in managing steroid-induced diabetes among patients undergoing glucocorticoid therapy.

Methods: The relevant data was obtained by reading many sources, including review papers from various publications that included keywords like glucocorticoids, hyperglycaemia, steroids, and herbal medications. Additionally, information was gathered from online sources.

Results: Steroid-induced diabetes mellitus (SIDM) represents a typical side effect stemming from an uncontrolled elevation of blood glucose level and it is closely related to the long-term damage and dysfunction caused by steroid use. The most commonly used medicinal plants to help manage blood glucose include Anethum graveolens, Gynura procumbens, Inula racemosa, and Gymnema Sylvestre, and the predominant mode of action for many herbal products and secondary metabolites employed in the management of steroid-induced diabetes revolves around modulating insulin signalling pathways.

Conclusion: Glucocorticoids may provoke hyperglycaemia by increasing insulin resistance, which increases hepatic gluconeogenesis while decreasing glucose absorption by peripheral tissues including muscle cells and adipocytes. Presently no current optimal treatment for steroid-induced diabetes is available. Herbal medications have been shown to effectively manage blood sugar levels by maintaining a steroid concentration.

Methods: This study was conducted in two parts. In the first part, 20 patients with primary hypothyroidism and serum thyrotropin (TSH) >30 mU/L were randomized into three groups receiving 1.6 μg/kg L-T4, equivalent doses of SRT3 or L-T3 of 0.55 μg/kg for 4 weeks. Their fasting serum-free T4 (fT4), T3, and TSH were measured weekly before taking medication for up to 4 weeks. In the second part, in 9 hypothyroid patients on L-T4 therapy and normal serum TSH, LT4 therapy was discontinued, and a once-daily dose of SRT3 of 0.55 μg/kg was replaced. Serum fT4, T3, and TSH were measured weekly.

Results: In part one, in patients treated with L-T3 and L-T4, serum TSH decreased to normal values after 4 weeks of intervention. In 7 patients on SRT3, serum T3 increased from 47 ± 12 at baseline to 110 ± 16 ng/dL, and serum TSH decreased from 60 ± 11 at baseline to 24 ± 10 and 26 ± 7 mU/L, respectively, at 14 and 21 days after intervention. At the end of 28 days, mean serum T3 was 110 ± 16, 168 ± 74, and 96 ± 18 ng/dL in SRT3, L-T3, and L-T4 groups, respectively (p < 0.001). In part two, serum fT4 decreased from 1.43 ± 0.7 to 0.41 ± 0.14 ng/dl, and serum T3 increased from 86 ± 21 to 113 ± 27 ng/dL by 21 days. Mean serum TSH remained normal until 14 days but increased to 15.1 ± 7.6 mU/L at 21 days. In the end, mean serum fT4, T3, and TSH were 0.35 ± 0.17 ng/dl, 77.4 ± 8.9 ng/dL, and 35 ± 11 mU/L, respectively.

Conclusion: In patients with primary hypothyroidism, SRT3 monotherapy with an equivalent dose to L-T4 maintained normal serum T3 but could not sustain normal serum TSH concentration.

Clinical Trial Registration Number: IRCT20100922004794N12.

Background: Patients with LADA tend to experience poorer glycaemic control, placing them at a higher risk of cardiovascular disease.

Objective: This study aimed to explore the relationship between osteocalcin levels and cardiometabolic risk factors, such as HbA1c, lipids, insulin resistance and obesity, in patients with LADA.

Methods: This retrospective study included 110 patients suffering from LADA with high glutamic acid decarboxylase (GAD) levels (≥180 IU/ml) and 286 with low GAD levels (<180 IU/ml) between January 2018 and December 2021. All participants were aged ≥30 years. Blood samples, collected after 8 hours of fasting, were analysed for osteocalcin and other biomarkers using chemiluminescence immunoassay. Logistic regression analysis assessed the relationship between osteocalcin and cardiometabolic risk factors.

Results: The LADA^high group had a lower body mass index (19.5 vs 23.4 kg/m², p = 0.014) and a lower proportion of obesity (19.1% vs 25.2%, p = 0.001) compared with the LADA^low group. Participants in the LADA^high group were slightly older (58.7 vs 58.3 years, p = 0.641). Fasting blood glucose was higher (8.9 vs 8.4 mmol/l, p = 0.068), and C-peptide was lower (1.0 vs 1.8 ng/ml, p = 0.024). Osteocalcin levels were significantly lower in the LADA^high group (12.19 vs 13.96 ng/ml, p = 0.004). Subgroup analyses revealed significant correlations, such as those between osteocalcin and HbA1c in the LADA^low group and an inverse relationship with triglyceride in men from the LADA^high group. Logistic regression analysis indicated that lower osteocalcin levels were significantly associated with a higher risk of poor glycaemic control and increased obesity.

Conclusion: Lower osteocalcin levels in patients with LADA with high GAD are associated with worse cardiometabolic parameters and increased cardiovascular risk. Osteocalcin may be a potential marker for assessing cardiometabolic risk in patients with LADA.