Case Presentation: The authors, hereby, highlight varied presentations of tertiary hyperparathyroidism (THPT) by presenting 3 interesting cases, describing their clinical course and outcomes. Through sharing these experiences and insights, we hope to contribute to a better understanding of THPT and its optimal management in patients with ESKD.

Conclusion: THPT can have a significant impact on patient health and quality of life. Despite the widespread use of interventions, such as vitamin D analogues, calcimimetics and parathyroidectomy, THPT remains a significant clinical challenge for patients with ESKD.

Objective: This study aimed to describe the demography of renal cancer in the Kingdom of Bahrain, comparing it to other regions worldwide, emphasizing the most common type of renal cancer, clinical presentation, and immunohistochemistry.

Methodology: This retrospective chart review comprises 74 Bahraini patients diagnosed with Renal neoplasms (from 2009-2019) at the Bahrain Defense Force (BDF) Hospital in the Kingdom of Bahrain. Variables collected include demographics, clinical presentation from patients’ electronic records and pathology registry, surgical management, immunohistochemistry, pathological staging, grading, and prognosis. IBM SPSS Statistics, version 28.0.0.0, was used.

Results: About 71 patients’ characteristics were analyzed; 63 had malignant neoplasms, and 8 had benign neoplasms. The mean age of patients with a malignant renal neoplasm was 56.38 (± 12.643). The most common presentation was an incidental finding (60.6% of lesions being right-sided). Clear Cell RCC was the most common malignant lesion (77.1%), and the most common stage was stage 1 (69.8%). CD10 and vimentin were 100% sensitive for Clear Cell RCC. No significant association was found between diabetes and a higher Fuhrman grade (3 or 4) (P = 0.066).

Conclusion: From 2009 to 2019, renal neoplasms incidence increased. The most common malignant neoplasm was clear cell RCC and among benign tumours was oncocytoma. Immunohistochemistry plays an important role in subtype determination. One recommendation would be to assess the incidence of renal neoplasms in other hospitals in Bahrain to establish more epidemiological data and compare our results with other Gulf hospitals.

Case Study: We report a case of the rare fibromyxoid variant of nephrogenic adenoma in the prostate urethra. To the best of our knowledge, only a few cases have been described in the literature.

Conclusion: This tumour can have variable morphological patterns with occasional worrisome features that can mimic carcinoma of the lower urinary tract.

Case Report: A 35-year-old male patient with a known metastatic lung neuroendocrine tumor (NET) who was treated with Sunitinib for many years with partial response and tolerating the treatment well-developed recurrent DIC on Sunitinib after COVID-19 infection.

Discussion: COVID-19 infection is reported to be associated with endothelial injury and inflammation. Vascular endothelial growth factor (VEGF) receptors have a role in the protection and modulation of endothelium. Sunitinib is a multikinase inhibitor with anti- VEGF effect. It is possible that endothelial injury after COVID-19 may have triggered recurrent DIC in this patient who had previously tolerated the same drug without problems.

Conclusion:

DIC may be underreported especially with antineoplastics having anti-VEGF effects. Potential risk, interaction, and association with COVID-19 infection in the Era of the pandemic are unclear but warrants further research, and drug-induced DIC should be considered in the differential diagnosis of such cases.

Methods: Via bioinformatics approaches, we identified the target miRNA. Subsequently, CCK-8, cell cycle analysis, and flow cytometry were used to check the biological influences of miR-29c-3p on ESCA cells. TransmiR, mirDIP, miRPathDB, and miRDB databases were used as tools for the prediction of upstream transcription factors and downstream genes of miR-29c-3p. The targeting relationship of genes was detected via RNA immunoprecipitation and chromatin immunoprecipitation, which was further validated by dual-luciferase assay. Finally, in vitro experiments revealed the way E2F1/miR-29c-3p/COL11A1 affected sorafenib’s sensitivity, and in vivo experiments were used to verify the way E2F1 and sorafenib impacted ESCA tumor growth.

Results: miR-29c-3p, downregulated in ESCA, could suppress ESCA cell viability, arrest the cell cycle in the G0/G1 phase, and impel apoptosis. E2F1 was found to be upregulated in ESCA and it could abate the transcriptional activity of miR-29c-3p. COL11A1 was found to be a downstream target of miR-29c-3p to enhance cell viability, induce cell cycle arrest in S phase, and constrain apoptosis. Cellular and animal experiments together demonstrated that E2F1 abated the sorafenib’s sensitivity of ESCA cells via miR-29c-3p/COL11A1.

Conclusion: E2F1 affected the viability, cell cycle, and apoptosis of ESCA cells by modulating miR-29c-3p/COL11A1, and it attenuated the sensitivity of ESCA cells to sorafenib, shedding new light on the treatment of ESCA.

Objective: This study examined the expression profile of FGFR3 in human synovial biopsy tissues and evaluated its gene-silencing effects on behaviors of synovial cells.

Methods: Immunohistochemical staining was used to measure FGFR3 expression in human RA joint tissues. Cell proliferation, migration, and apoptosis assays were used to monitor behavioral changes in cultured synovial SW-982 cells with siRNA-mediated FGFR3 gene silencing. Immunofluorescent staining and western blotting were used to detect molecular changes in the FGFR3 gene-silenced cells.

Results: FGFR3 up-regulation was noted in both cytoplasms and nuclei of synovial cells in human RA joints. FGFR3 siRNA delivery experiments corroborated that FGFR3 knockdown decreased proliferation and migration, and triggered apoptosis of synovial cells. The FGFR3 gene knockdown enhanced constitutive expression of epithelial marker E-cadherin and conversely suppressed expression of epithelial-mesenchymal transition (EMT) markers, including Snail, fibronectin, and vimentin. In addition, FGFR3 silencing significantly reduced the constitutive expressions of TNF-α, transcription factor NF-κΒ, and downstream COX-2 protein and collagenolytic enzyme MMP-9. MAPK inhibition markedly suppressed constitutive levels of NF-κΒ, COX-2, and MMP-9.

Conclusion: Genetic interference of FGFR3 could modulate the expression of inflammatory mediators and EMT markers in the synovial cells. Targeting the FGFR3/MAPK signal axis may be considered a useful therapeutic strategy to ameliorate the development of RA.

Objective: In this comprehensive review, we have elaborated on the pathophysiology, and various signaling pathways linked with Sarcopenia. Also, discussed the preclinical models and current interventional therapeutics to treat muscle wasting in older patients.

Conclusion: In a nutshell, a comprehensive description of the pathophysiology, mechanisms, animal models, and interventions of Sarcopenia. We also shed light on pharmacotherapeutics present in clinical trials which are being developed as potential therapeutic options for wasting diseases. Thus, this review could fill in the knowledge gaps regarding Sarcopenia-related muscle loss and muscle quality for both researchers and clinicians.

Introduction: CBP/β-catenin antagonists rebalance the equilibrium between CBP/β-catenin and p300/β-catenin dependent transcription and may be able to treat or prevent many diseases of aging via maintenance of somatic stem cell pool and regulating mitochondrial function and metabolism involved in differentiation and immune cell function. The safety, efficacy, and therapeutic potential of the specific CBP/β-catenin antagonists, ICG-001, and the second-generation compound, C82, the active agent derived from the pro-drug PRI-724, have been studied extensively in a variety of preclinical disease models and in the clinic for oncology and hepatic fibrosis. However, the lack of oral bioavailability has hampered the further development of PRI-724. Thus, Eisai recently proposed a third-generation, orally available, reportedly CBP/β-catenin antagonist E7386. Here, we have performed a comparative analysis of E7386 with the highly specific bona fide CBP/β-catenin antagonists, ICG-001 and C82.

Methods: We utilized a series of previously validated biochemical and transcriptional assays to investigate the selective targeting of the CBP/β-catenin interaction in conjunction with global transcriptional profiling to compare the three small molecules, ICG-001, C82, and E7386.

Result: Our data cast significant doubt that the mechanism of action of E7386 is via specific CBP/β-catenin antagonism.

Conclusion: It can thus be concluded that E7386 is not a specific CBP/β-catenin antagonist.

Methods: To investigate IMPDH2 expression in HB tissues and prognostic significance in HB patients, gene expression profiling interactive analysis (GEPIA) has been adopted. Immunohistochemistry has also helped to validate the protein expression of IMPDH2 in HB tissues. The effect of IMPDH2 overexpression or depletion on the proliferation of Hepatoblastoma cells in vitro has been evaluated by CCK8 assays and colony formation assays. Xenograft tumor growth of mice has been detected. Luciferase reporter assays have been conducted to determine the interaction of IMPDH2 and JunB, which was further asserted by pharmacological inhibition of JunB.

Results: IMPDH2 was highly expressed in HB tissues. Experimentally, the proliferation and colony formation of HuH6 cells were increased by IMPDH2 overexpression. Conversely, genetic inactivation of IMPDH2 impaired the proliferative efficiency and colony-forming rate of HepG2 cells. Besides, the luciferase reporter assay validated IMPDH2 overexpression to be associated with enhanced JunB transcriptional activity, while its activity was diminished in the case of IMPDH2 depletion. JunB inhibitor neutralized the IMPDH2-mediated increased phosphorylation of JunB.

Conclusion: Our findings, thus, suggest that IMPDH2 exhibits its oncogenic role in HB partially via JunB-dependent proliferation.

Objective: The aim of this review was to discuss several important deregulated miRNAs that are involved in the p53 signaling pathway in BC, especially the TNBC subtype. Finally, miRNAs’ involvement in tumor properties and their applications as diagnostic, prognostic, and therapeutic agents have been elaborated in detail.

Results: The miRNA expression profile of BC is involved in tumor-grade estrogen receptor (ER) and progesterone receptor (PR) expression, and other pathological properties from luminal A to TNBC/basal-like subtypes via p53 signaling pathways.

Conclusion: Developing our knowledge about miRNA expression profile in BC, as well as molecular mechanisms of initiation and progression of BC can help to find new prognostic, diagnostic, and therapeutic biomarkers, which can lead to a suitable treatment for BC patients.

Background: GBM is the most malignant primary brain cancer with a poor prognosis. Previous studies have suggested that GBM vessels undergo dynamic remodeling modulated by tumor vasodilation and vasoconstriction instead of tumor angiogenesis.

Objective: Here, we have first investigated the expression and function of UTS2, a potent vasoconstrictor, in GBM.

Methods: The mRNA expression profiles and clinical information of GBM patients were obtained from the TCGA database. The clinical relevance of UTS2 was explored by the Mann-Whitney U test and Cox hazard regression survival test. We further explored the role of UTS2 in GBM cell proliferation, migration, and tumor immune microenvironment. Moreover, we established the in vivo mice model to validate its oncogenic effects on GBM progression.

Results: Although we did not find significant correlations between UTS2 expression and patients’ clinical characteristics, UTS2 was identified as a valid independent prognostic indicator according to multivariate survival analysis. Knockdown of UTS2 resulted in decreased GBM cell proliferation and migration. In addition, functional enrichment analysis implied UTS2 to be involved in the regulation of the immune microenvironment. In vivo studies showed that UTS2 knockdown suppressed GBM xenograft growth, highlighting the tumor-promoting effects of UTS2 on GBM.

Conclusion: Our study identified that UTS2 could predict the prognosis of GBM patients and provided evidence regarding its oncogenic effects both in vitro and in vivo.

Objective: This study investigated the discriminatory power of the stretched-exponential model and fractional-order calculus model parameters for hepatocellular carcinoma versus intrahepatic cholangiocarcinoma in orthotopic xenograft nude mice.

Methods: Prototype orthotopic xenograft models of hepatocellular carcinoma and intrahepatic cholangiocarcinoma were developed using 20 nude mice divided into two groups and separately transplanted with MHCC97H and HUCCT1 cells. Readout-segmented diffusion-weighted imaging with multiple b-values (0-2000 s/mm²) was obtained using a 3.0-T magnetic resonance imaging scanner. The apparent diffusion coefficient was calculated using the mono-exponential model. The distributed diffusion coefficient and intravoxel water molecular diffusion heterogeneity (α) were calculated using the stretched-exponential model. The diffusion coefficient (D), fractional-order derivative in space (β), and spatial parameter (μ) were calculated using the fractional-order calculus model. The liver and tumor specimens of nude mice were immunostained after euthanasia to clarify the liver cancer type. Differences in diffusion-related parameters between the groups were evaluated using Mann-Whitney U-test and univariate logistic analysis. Receiver operating characteristic curves were used to assess the diagnostic efficacy of each parameter. P<0.05 was deemed significant.

Results: α, D, and β were significant discriminators between the groups. The area under the curve for these three variables was 0.890, 0.830, and 0.870, respectively, with cutoff values of 0.491, 0.435, and 0.782, respectively.

Conclusion: The stretched-exponential model parameters α and the fractional-order calculus model parameters D and β showed high diagnostic efficacy in discriminating intrahepatic cholangiocarcinoma from hepatocellular carcinoma in orthotopic xenograft nude mouse models.

Methods: This retrospective study comprised 27 patients diagnosed with 29 tumors of CCPRCC. The study was approved by the Medical Ethics Committee and the requirement for the informed consent was waived. The inclusion criteria stipulated pathology-confirmed CCPRCCs with at least one preoperative imaging examination, including CT or MRI. Two experienced radiologists independently analyzed the imaging characteristics, including size, location, growth mode, morphology, texture, density, and enhancement pattern. Paired t-test was used to compare differences in CT Hounsfield unit values and apparent diffusion coefficient (ADC) imaging between the tumor and the renal cortex.

Results: The mean age of the 27 patients was 57.0 ± 14.2 years. Nineteen patients underwent CT, while 12 underwent MRI (There are 4 patients underwent not only CT but also MRI). Among the cases, 26 (96%) were single, and 1 (4%) was multiple, consisting of three lesions. Out of the 29 tumors, 15 (52%) were located in the left kidney and 14 (48%) in the right kidney. The mean tumor diameter was 3.3 ± 1.7 cm. Furthermore, 19 (66%), 3 (10%), and 7 (24%) tumors were solid, cystic, mixed solid, and cystic type, respectively. The growth mode was endogenous and exogenous in 8 (28%) and 21 (72%) tumors, respectively. The tumor shape was irregular and round in 5 (17%) and 24 (83%) tumors, respectively. The CT value of the tumor was approximately 33.2 ± 9.8 HU, which was not significantly different from that of the renal cortex(31.1 ± 6.3HU)(p = 0.343). Furthermore, 7 (24%), 12 (41%), and 3 (10%) had calcification, cystic degeneration, and hemorrhage, respectively. In 12 tumors, hypointense and hyperintense were predominant on T1 and T2-weighted images, respectively. The tumor capsule was found at the edge of 12 tumors. The average ADC value of the tumor (1.54 ± 0.74 × 10⁻³ mm²/s) and that of the renal cortex(1.68 ± 0.63×10–3mm2 /s) was not statistically significantly different (p = 0.260). The enhancement scanning revealed “wash-in and wash-out” enhancement in 19 (68%) tumors, continuous or progressive enhancement in 6 (21%) tumors, and enhanced cystic wall and central separation in 3 (11%) tumors.

Conclusion: CCPRCC occurs more likely in middle-aged and elderly individuals, and the tumor is prone to cystic degeneration, with rare bleeding and calcification, and no obvious limitation on MRI diffusion-weighted imaging, which enhancement form performs as mainly “wash-in and washout,” but the final diagnosis depends on histopathology.

Objective: This study aimed to evaluate ultrasound-based radiomics for predicting outcomes in HBV-ACLF.

Methods: We enrolled 264 HBV-ACLF patients, dividing them into a training cohort (n=184) and a validation cohort (n=80). From hepatic ultrasound images, 455 radiomic features were extracted. Radiomics-based phenotypes were identified through unsupervised hierarchical clustering. A radiomic signature was developed using a Cox-LASSO algorithm to predict 30-day mortality. Furthermore, we integrated the signature with independent clinical predictors via multivariate Cox regression to construct a combined clinical-radiomic nomogram (CCR-nomogram). Integrated discrimination improvement (IDI) and net reclassification improvement (NRI) assessed performance improvements achieved by adding radiomic features to clinical data.

Results: Both clustering and radiomic signature identified two distinct subgroups with significant differences in clinical characteristics and 30-day prognosis. In the training cohort, the signature achieved a C-index of 0.746, replicated in validation with a C-index of 0.747. The CCR-nomogram achieved C-indices of 0.834 and 0.819 for the training and validation cohorts. Incorporating radiomic features significantly improved the CCRnomogram over the signature and clinical-only models, evidenced by IDI of 0.108-0.264 and NRI of 0.292-0.540 in both cohorts (all p0.05).

Conclusion: Ultrasound-based radiomics offered prognostic information complementary to clinical data and demonstrated potential to enhance outcome prediction in HBV-ACLF.

Case Presentation: We present a case of a solid cystic renal mass that was evaluated by contrast-enhanced ultrasound (CEUS) during an imaging workup. The patient underwent nephrectomy and histopathological confirmation of MESTK. The lesions showed hypoenhancement during the process. Quantitative perfusion analysis showed the septation of the solid cystic lesion to have lower peak enhancement with a longer rise time compared to the normal renal cortex.

Discussion: CEUS can visualize the microcirculation of the organ and reconstruction of the vessels. By providing a more detailed visualization of the microvessel, CEUS is a useful tool for further characterizing renal lesions that show indeterminate enhancement on CT. This study determined the time to peak to be shorter for the cancerous lesion than the normal renal cortex, while peak intensity did not differ between the cancerous lesion and the normal renal cortex.

Conclusion: Quantitative perfusion analysis of CEUS may be useful for differentiating benign and malignant solid cystic renal masses. Further investigation is needed to determine whether peak intensity is a useful parameter in differentiating benign and malignant solid cystic lesions of the kidney.

Methods: From December 2020 to December 2021, patients who underwent imaging-guided RFA of CRLM at our hospital with available CT/MRI images were enrolled consecutively. 22 patients with 46 lesions had undergone conventional group RFA whereas 29 patients with 63 lesions had undergone fusion group RFA. The lesion detection rate, technical success, local tumor progression (LTP) and complications were calculated.

Results: In this retrospective study, 51 patients with 130 lesions were diagnosed with CRLM. However, there were 12 lesions and 9 lesions invisible in the conventional group and fusion group, respectively. The lesion detection rate on the fusion imaging was significantly higher than on the US or CEUS in the fusion group (P<0.05). There were no significant differences of the detection rate between the conventional group and the fusion group (P=0.207). In both groups, the technical success rate was 100%. For local tumor progression (LTP), there were no significant differences between the two groups (P>0.05). The complications after ablation had no significant differences between the two groups (P=0.97).

Conclusion: CEUS/ Gd-EOB-DTPA-enhanced MRI fusion imaging is a safe and effective method for RFA in the management of CRLM patients, and it may improve the therapeutic effect by detecting small lesions early.

Objective: To investigate the ultrasonographic features and diagnostic value of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion in children and adolescents.

Materials and Methods: The clinical and ultrasonographic data of 10 patients with renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion confirmed by pathology in our hospital were analyzed retrospectively. The age ranged from 3 to 18 years old, including 7 males and 3 females. The tumor location, size, boundary, echo, hemorrhage, cystic change, calcification, blood flow, lymph node status and metastasis were mainly observed, and the results were compared with the pathological results.

Results: There were 10 masses in 10 cases of renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion, including 4 in the right kidney and 6 in the left kidney; the maximum diameter line is 5-23cm; 9 cases had clear mass boundary (90%); 9 masses (90%) showed mixed cystic and solid masses with high echo of solid components, and 1 mass (10%) showed huge multilocular cystic mass with multiple septations; necrosis and cystic changes were seen in all 10 masses (100%); calcification in 5 masses (50%); blood flow signals were seen in the solid components of the mass (100%).

Conclusion: Renal cell carcinoma associated with Xp11.2 translocation/TFE3 gene fusion in children and adolescents are mostly large cystic and solid mixed echo masses, with high echo of solid components, and often accompanied by cystic changes and calcification. Its ultrasonic manifestations have certain characteristics. Color Doppler ultrasound has a certain diagnostic value for this disease.

Case Report: A 21-year-old male patient with a solitary kidney who had been diagnosed since birth presented with abdominal pain. Transabdominal and transrectal ultrasonography (US), computed tomography (CT), and MRI were performed. The contrast-enhanced MRI of the pelvis showed a tubular fluid-filled, macrolobulated lesion measuring 6 x 6 x 4 cm, mildly high signal intensity in the T2-weighted images, and slightly high signal intensity in the T1-weighted images, without contrast enhancement. The left kidney was hypoplasic. Imaging findings led to the diagnosis of Zinner’s syndrome, and conservative treatment was planned.

Discussion: Zinner’s syndrome is characterized by a triad consisting of unilateral renal agenesis or hypoplasia, ipsilateral seminal vesicle cyst, and ipsilateral ejaculatory duct obstruction. MRI is the modality of choice for an impeccable depiction of the anatomy of the male genital tract, for demonstrating the seminal vesicles and evaluating anomalies of the mesonephric duct. It is also useful in distinguishing seminal vesicle cysts from other cystic pelvic masses.

Conclusion: Zinner’s syndrome should be considered when diagnosing cystic pelvic masses in males with renal agenesis or hypoplasia. Because of its high soft tissue contrast resolution, MRI is the gold standard modality for confirming the diagnosis and assessing the cyst’s origin and contents.

Objective This study aimed to overcome the problem related to identifying kidney stone composition; we need an accurate method to analyze the composition of kidney stones.

Methods In this paper, we proposed the automatic kidney stone composition analysis algorithm based on a dual-energy CT image. The algorithm first segmented the kidney stone mask by deep learning model, then analyzed the composition of each stone by machine learning model.

Results The experimental results indicate that the proposed algorithm can segment kidney stones accurately (AUC=0.96) and predict kidney stone composition accurately (mean Acc=0.86, mean Se=0.75, mean Sp=0.9, mean F1=0.75, mean AUC=0.83, MR (Exact match ratio)=0.6).

Conclusion The proposed method can predict the composition and location of kidney stones, which can guide its treatment.

Experimental results show that the weighting strategy can improve kidney stone segmentation performance. In addition, the multi-label classification model can predict kidney stone composition precisely, including the mixed composition kidney stones.

Case Presentation: We report a case of a 73-year-old patient with small intestinal smooth muscle sarcoma with hepatic metastasis. No significant abnormalities were seen on examination of the abdomen. We performed abdominal enhancement CT, contrast-enhanced ultrasonography (CEUS), and ultrasoundguided pelvic mass puncture biopsy, and we found a heterogeneous density and echogenicity of the pelvic mass, and the enhancement was progressive with sustained hyperenhancement. The postoperative pathology was smooth muscle sarcoma of the small intestine. The typical fast-in, fast-out bull's-eye sign of metastases, characterized the liver presented with multiple hypodense and echogenic nodules and the enhancement. The clinical presentation, imaging, histologic features, and treatment are also discussed in this article.

Conclusion: This article briefly reviews the literature on small intestinal leiomyosarcoma. The purpose of this case report is to emphasize the specificity of the case and evaluate the imaging presentation of ultrasound (US) and CEUS and the main differential diagnosis of this rare gastrointestinal tumor.

Materials and Methods: This was a retrospective cohort study. Patients were divided into two groups according to the stage of cervical cancer. The mean term of pregnancy at the time of the diagnosis was the early second trimester (range 10-27 weeks) and the median age was 33 years (range 26-40 years). The abdominal and pelvic MRI images and clinical data of these patients were reviewed. Tumor size, local tumor spread, and nodal involvement were evaluated using an MRI dataset. The treatment and follow-up imaging were analyzed as well, and the ADC was measured before and after the chemotherapy.

Results: 16 patients with histopathologically confirmed cervical cancer during pregnancy were retrospectively enrolled. 7 patients were diagnosed with local cervical cancer (FIGO stage IAI) and designated as early stage group, as the lesion was invisible on MRI. In this group, pregnancies were allowed to continue until cesarean delivery (CD) at 38-41 weeks. The other 9 patients presenting with local or extensive cervical cancer (FIGO stage IB2-IIA2) were designated as the advanced-stage group. The lesion could be measured and analyzed on MRI. They were treated with neoadjuvant chemotherapy in pregnancy. Among them, 6 patients underwent TP regimen (paclitaxel 135~175 mg/m2 plus cisplatin 70~75 mg/m2), while 3 patients received TC regimen (paclitaxel 135~175 mg/m2 plus carboplatin AUC=5). NACT was performed for 1 to 2 courses before surgery. ADC demonstrated significant differences before and after chemotherapy administered during pregnancy (1.06 ± 0.12 sec/mm2 vs. 1.34 ± 0.21 sec/mm2).

Conclusion: MRI has been found to be helpful in staging cervical cancer in pregnancy. Patients with stage IA confirmed by MRI can choose conservative treatment and continue the pregnancy until term birth. MRI can dynamically monitor the efficacy of chemotherapy for patients with stage IB and above during pregnancy. ADC value can have a potential role in the evaluation of chemotherapy efficacy.

Objective: To explore the clinical significance of renal lesions with low-level enhancement on CT after exposure to anti-cancer drugs.

Methods: Medical records of patients with cancer who developed renal lesions on CT after exposure to anti-cancer drugs were retrospectively reviewed. Renal lesions were scored according to the extent of involvement, CT attenuation values of lesions and normal parenchyma were measured on precontrast CT and three phases of contrast-enhanced CT, and changes in serum creatinine (SCr) from one week before exposure to drugs to one week before and after the appearance of renal lesions were recorded.

Results: This study included 54 patients (86 lesions). Lesions were slightly lower density on pre-contrast CT, and less enhancing than normal renal parenchyma, especially in the delayed phase. Lesions were wedge-shaped, and involved the renal pyramid and associated renal cortex, as well as, were single or multiple, and occurred in the unilateral or bilateral kidneys. There were patchy and cord-like shadows of increased density in adjacent perirenal adipose tissue. During follow-up, lesions disappeared in 15 patients and persisted in 39 patients without significant progression. There were significant differences in renal lesions and normal renal parenchyma CT attenuation values in each phase of contrast-enhanced CT. Change in SCr level was significantly positively correlated with lesion score.

Conclusion: Renal lesions with low-level enhancement on CT suggest early drug-induced kidney injury. These findings will inform clinical decision-making.

Methods: Demographic data, pathology results, cancer stages, and hospitalization duration of 104 patients undergoing surgery at the urology clinic due to renal cell carcinoma between 2019 and 2023 were analyzed retrospectively. On computed tomography scans acquired during diagnosis, visceral adipose tissue, subcutaneous adipose tissue, total adipose tissue, and skeletal muscle area were measured. The ratios of body composition parameters were computed.

Results: When the correlation between survival time and body composition in deceased patients was analysed, a moderate but significant correlation was observed between skeletal muscle area value and total adipose tissue / skeletal muscle area ratio (r=0.630, p=0.001; r=0.598, p=0.002). A significant and strong correlation was observed between total adipose tissue value and survival (r=0.704, p<0.001). Subcutaneous adipose tissue / skeletal muscle area was found to be an independent risk factor associated with mortality, and a ratio of 0.98 or less increased the mortality risk approximately 16-fold.

Conclusion: The relationship between body composition parameters measured by computed tomography, which can be easily evaluated pre-treatment, and mortality, postoperative recovery and length of hospital stay can be evaluated, giving clinicians an idea about the potential difficulties that patients may encounter during the treatment process. For this purpose, the subcutaneous adipose tissue / skeletal muscle area ratio is the most helpful parameter that can be used.

Objective: To investigate the clinical value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in assessing renal pathological injury in patients with immunoglobulin A (IgA) nephropathy compared with a mono-exponential model.

Methods: Altogether, 80 patients with IgA nephropathy were divided into the mild (41 cases) andmoderate–severe (m–s) renal injury groups (39 cases) according to pathology scores, and 20 healthy volunteers were recruited as controls. All participants underwent IVIM-DWI of the kidneys, and renal parenchymal apparent diffusion coefficient (ADC), pure molecular diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) values were measured. One-way analysis of variance, receiver operating characteristic (ROC) curve analysis, and Pearson correlation analysis were performed for all the DWI-derived parameters.

Results: The DWI-derived parameters of the m–s renal injury group were significantly lower than those of the mild renal injury and control groups (P < 0.01). The ROC analysis revealed that f had the largest area under the ROC curve for differentiation between the m–s and mild renal injury groups and between the m–s renal injury and control groups. The f had the largest correlation coefficient with renal pathology scores (r=−0.81), followed by the D* (−0.69), ADC (−0.54), and D values (−0.53), respectively (all P<0.01).

Conclusion: IVIM-DWI demonstrated better diagnostic performance than the mono-exponential model in assessing renal pathological injury in patients with IgA nephropathy.

Case Report: A 52-year-old male patient was admitted to our clinic with the diagnosis of an incidental right renal mass. On contrast-enhanced abdominal CT revealed a mass reaching approximately 8 cm in diameter in the right kidney located in the middle pole. On contrast-enhanced thorax, CT showed a metastatic lesion in the left main bronchus bifurcation. The patient underwent an open radical nephrectomy with the diagnosis of an oligometastatic right renal mass. His pathology was reported as clear cell renal cell carcinoma (ccRCC). The patient was referred to the medical oncology clinic for immunotherapy. The metastatic lesion in the lung completely regressed in the follow-up of the patient who was started on Chek point inhibitors. However, he was referred to our clinic after an incidental metachronous mass was detected in the contralateral left adrenal in FDG PET/CT (SUVmax: 6.7) in 1st year. Dynamic contrast-enhanced MRI was performed to reevaluate and for mass characterization, and a 4 cm mass was observed in the left contralateral adrenal. Laparoscopic metastasectomy was performed for the left adrenal mass. No recurrence or adrenal insufficiency developed in the 6-month follow-up after discharge.

Conclusion: Transperitoneal adrenalectomy is a minimally invasive method that can be safely performed in metastatic adrenal masses. Although contralateral adrenal metastasis is rare in ccRCC, it should be kept in mind that adrenal metastasis may develop in the late period in patients with a history of renal cancer.

Materials and Methods: Patients who had undergone pelvic DWI, intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI) sequence MRI scan before surgery were retrospectively enrolled. Single index model, double index model, and DKI were used for post-processing of the DWI data, and the apparent diffusion coefficient (ADC), real diffusion coefficient (D), pseudo diffusion coefficient (D*), perfusion fraction (f), non-Gaussian mean diffusion kurtosis (MK), mean diffusion coefficient (MD) and anisotropy fraction (FA) were calculated and compared between the Ki-67 high (≥50%) and low (<50%) expression groups.

Results: Forty-two patients with a median age of 56 (range 37 - 75) years were enrolled, including 15 patients with a high Ki-67 (≥50%) expression and 27 with a low Ki-67 (<50%) expression. The MK (0.91 ± 0.12 vs. 0.76 ± 0.12) was significantly (P<0.05) higher while MD (0.99 ± 0.17 vs. 1.16 ± 0.22), D (0.55 ± 0.06 vs. 0.62 ± 0.08), and f (0.21 vs. 0.28) were significantly (P<0.05) lower in the high than in the low expression group. The combined model of MK, MD, D, and f-values had the largest area under the curve (AUC) value of 0.869 (95% CI: 0.764-0.974), sensitivity 0.733 and specificity 0.852, followed by the MK value with an AUC value 0.827 (95% CI: 0.700-0.954), sensitivity 0.733 and specificity 0.815.

Conclusions: IVIM and DKI have certain diagnostic values for preoperative evaluation of the EC Ki-67 expression, and the combined model has the highest diagnostic efficiency.

Methods: Sixty-four patients with single pulmonary lesions (SPLs) received DCE-MRI at 3.0 T. Of them, 49 cases were diagnosed with lung cancer, and 15 with benign pulmonary nodules (8 inflammatory nodules, 5 tuberculosis, and 2 abscesses). SPLs were quantitatively analyzed to determine the pulmonary lesions-related perfusion parameters, including reflux constant (Kep), volume transfer constant (K_trans), the maximum slope of increase (MaxSlope), extravascular extracellular space volume fraction (Ve), apparent diffusion coefficient (ADC), the initial area in the signal intensitytime curve (IAUGC), and contrast-enhancement ratio (CER). In addition, a Student’s t-test was conducted to calculate statistical significance regarding the quantitatively analyzed perfusion parameters in benign SPLs compared to malignant SPLs. The area under (AUC) the receiver operating characteristic (ROC) curve was studied to investigate the performance of perfusion parameters in diagnosing lung cancer.

Results: Values of K_trans, Kep, Ve, MaxSlope, and IAUGC increased within malignant nodules relative to benign nodules (K_trans: 0.21 ±0.08 vs. 0.73 ±0.40, P = 0.0001; Kep: 1.21 ±0.66 vs. 1.83 ±0.90, P = 0.0163; Ve: 0.24 ±0.08 vs. 0.47 ±0.18, P < 0.0001; MaxSlope: 0.09 ±0.14 vs. 0.28 ±0.29, P = 0.0166; IAUGC: 0.18 ±0.09 vs. 0.55 ±0.34, P = 0.0001). Meanwhile, malignant nodules presented higher ADC than benign nodules (0.0016 ±0.0006 vs. 0.0012 ±0.0003, P = 0.0019). K_trans and IAUGC showed the best diagnostic performance with AUCs [1.0, 95%CI (0.99–1.0); 0.93, 95%CI(0.85–1.0), respectively].

Conclusion: Malignant pulmonary lesions had higher values of K_trans, Ve, Kep, MaxSlope, and IAUGC compared to benign pulmonary lesions. Overall, perfusion parameters of DCE-MRI facilitate discrimination between benign from malignant pulmonary nodules.

Objective: The aim of this study was to construct and validate a radiomics model based on contrast-enhanced CT to predict the GPC3 expression in HCC.

Methods: This retrospective study included 141 (training cohort: n = 100; validation cohort: n = 41) pathologically confirmed HCC patients. Radiomics features were extracted from the Artery Phase (AP) images of contrast-enhanced CT. Logistic regression with the Least Absolute Shrinkage and Selection Operator (LASSO) regularization was used to select features to construct radiomics score (Rad-score). A final combined model, including the Rad-score of the selected features and clinical risk factors, was established. Receiver Operating Characteristic (ROC) curve analysis, Delong test, and Decision Curve Analysis (DCA) were used to assess the predictive performance of the clinical and radiomics models.

Results: 5 features were selected to construct the AP radiomics model of contrast-enhanced CT. The radiomics model of AP from contrast-enhanced CT was superior to the clinical model of AFP in training cohorts (P < 0.001), but not superior to the clinical model in validation cohorts (P = 0.151). The combined model (AUC = 0.867 vs. 0.895), including AP Rad-score and serum Alpha-Fetoprotein (AFP) levels, improved the predictive performance more than the AFP model (AUC = 0.651 vs. 0.718) in the training and validation cohorts. The combined model, with a higher decision curve indicating more net benefit, exhibited a better predictive performance than the AP radiomics model. DCA revealed that at a range threshold probability approximately above 60%, the combined model added more net benefit compared to the AP radiomics model of contrastenhanced CT.

Conclusion: A combined model including AP Rad-score and serum AFP levels based on contrast-enhanced CT could preoperatively predict GPC3-positive expression in HCC.

Objective: To describe the imaging characteristics of GCCMs and study the reasons for preoperative misdiagnosis.

Methods: We retrospectively analyzed the data of 12 patients (5 men, 7 women; mean age, 35.23 ± 12.64 years) with histopathologically confirmed GCCMs. Two radiologists analyzed the CT (n = 12) and MRI (n = 10) features: location, number, size, shape, boundary, signal intensity, and enhancement.

Results: The sellar region, cerebral hemisphere, skull bone, and ventricle were involved in 5, 4, 2, and 1 patients, respectively. Three tumors were irregularly shaped, while nine were oval. Eleven lesions showed slightly high- and/or high-density on CT; 1 lesion appeared as a low-density cyst. Calcifications were found in 11 lesions. Four tumors showed uniform hypointensity on T1-weighted imaging (T1WI) and hyperintense signals on T2-weighted imaging (T2WI). Six tumors showed mixed low-, equal-, and high-intensity signals on T1WI and T2WI. Noticeable contrast enhancement and gradual strengthening were noted on T1WI. Ten lesions showed hemorrhage and hemosiderin deposition. The GCCMs were wrongly diagnosed as cartilage-derived tumors/ meningioma (3 patients); tumor and hematoma (2 patients each); and pituitary tumor/ meningioma, chondroma, chordoma, ependymoma, and macroadenoma (1 patient each).

Conclusions: GCCMs present as an oval mass with slightly high- and/or high-density calcifications on CT and show hemorrhage and hemosiderin accumulation on MRI. Therefore, slightly high- and/or high-density calcification and hemosiderin accumulation are critical clinical characteristics of GCCMs.

Objectives: This research aimed to independently validate the performance of machine learning-based ultrasound (US) radiomics analysis in differentiating benign from malignant SRM, and to compare its performance with that of radiologists.

Methods: A total of 499 patients from two hospitals were retrospectively included in this study and divided into two cohorts. US images were used to extract radiomics features. To obtain the most robust features, inter-observer correlation coefficient, Spearman correlation coefficient, and least absolute shrinkage and selection operator methods were applied for feature selection. Three models were developed in the training data using the stochastic gradient boosting algorithm, including a clinical model, a radiomics model, and a combined model that integrated clinical factors and radiomics features. The performance of these models was evaluated in the independent external validation data, including discrimination, calibration, and clinical usefulness, and compared with pooled radiologists' assessments.

Results: The AUCs of the clinical, radiomics, and combined models were 0.844, 0.942, and 0.954, respectively. The radiomics and combined models significantly outperformed the clinical model (all p < 0.05), while no significant difference was observed between them (p = 0.32). The radiomics and combined models showed good discrimination and calibration. Decision curve analysis exhibited that the combined model had clinical usefulness. Compared with the pooled radiologists’ assessment (AUC, 0.799), the combined model showed superior classification results (p < 0.01) and higher specificity (p < 0.01) with similar sensitivity (p = 0.62).

Conclusion: The combined model incorporating clinical factors and radiomics features accurately distinguished benign from malignant SRM.

Case Description: A 57-year-old male presented to our hospital with right upper quadrant abdominal pain. Ultrasonography, computed tomography, and magnetic resonance imaging revealed a large mass with a well-defined margin in the right hemiliver. The patient underwent a right hemihepatectomy, and the final histopathology revealed clear cell-type HCC.

Conclusion: Distinguishing clear cell types from other types of HCC solely based on radiological findings is challenging. If hepatic tumors exhibit encapsulated margins, enhancing rims, intratumoral fat, and arterial phase hyperenhancement/washout pattern despite their large size, consideration of clear cell subtypes in the differential diagnosis list will aid patient management, implying better prognosis than not-otherwise-specified HCC.

Case Presentation: A chest CT scan of a 72-year-old man with suspected chronic pneumonia revealed a well-defined consolidation in the upper lobe of the left lung. The lesion was slightly enlarged at the 9-month follow-up, and low FDG accumulation was subsequently observed using 18F-fluorodeoxyglucose (18F-FDG) PET/CT scans. The patient was later diagnosed with PEAC through percutaneous lung biopsy.

Conclusion: Our case has demonstrated specific imaging findings of PEAC.

Methods: The patients with solid renal mass histopathological diagnosed after excision or tru-cat biopsy who underwent a preoperative ARFI elastography of the lesion during a 4-year period were included in this study. Preoperative shear wave velocity (SWV) values were measured in all the lesions. SWV results of RCCs and oncocytomas were compared by an independent t-test, and cut-off, sensitivity and specificity values were calculated.

Results: Forty-two of the 60 patients included in the study were men (70%) and, 18 were women (30%), and the mean age was 59.7 ± 14 (27-94) years. Among 46 RCCs (76.6%), 23 and 14 oncocytomas, 5 (23.4%) were located in the right kidney (p:0.34722). Mean SWV values were found to be significantly higher in RCCs (2.87± 0.74 (0.96-4.14) m/s) than oncocytomas (1.83 ± 0.78 (0.80-3.76) m/s) (p <0.001). In the ROC analysis, a cutoff value of 2.29 m/s was found to havean 80.4% sensitivity and a 78.6% specificity for the discrimination of RCCs from oncocytomas.

Conclusion: ARFI elastography measurements may be useful in distinguishing RCC and oncocytomas that may have similar solid radiological imaging features.

Case Presentation: A 46-year-old middle adulthood male presented with unexplained fever, night sweats, abdominal distension for 3 months, and weight loss of around 7kg during almost 6 months, which is extremely similar to lymphoma from the clinical features and imaging examinations. After a clear diagnosis, the case not only obtained the opportunity of surgery but was also exempted from radiotherapy. The treatment effect was good. We report a case of rare metastatic embryonal carcinoma, which can provide insight into the diagnosis and treatment of embryonal carcinoma.

Conclusion: Metastatic embryonal carcinoma of abdominal lymph nodes can be highly similar to lymphoma; the diagnosis can only be based on clinical manifestations and imaging examination but also combined with patient history, tumor markers and biochemical examination. However, the final diagnosis depends on pathological biopsy.

Methods: A retrospective analysis was conducted on a patient with synchronous CRC and ccRCC who underwent ¹⁸F-FDG PET/CT and contrast-enhanced CT before treatment. Databases were analyzed to identify differentially expressed genes between CRC and ccRCC, and co-expression genes were extracted for RCC and CRC.

Results: ¹⁸F-FDG PET/CT revealed intense metabolic activity in the primary colorectal lesion (SUVmax 13.2), while a left renal mass (diameter = 35 mm) was observed with no significant uptake. Contrast-enhanced CT during the arterial phase showed heterogeneous intense enhancement of the renal lesion, and the lesion washed out earlier than in the renal cortex in the nephrographic and excretory phases, indicating ccRCC. The histopathological results confirmed synchronous double primary malignant tumors. Our bioinformatic analysis results showed that synchronous occurrence of CRC and ccRCC may correlate with simultaneous expression of Carbonic Anhydrase 9 (CA9), integrin-binding sialoprotein (IBSP), and Fibrinogen γ chain (FGG).

Conclusion: ¹⁸F-FDG PET/CT combined with contrast-enhanced CT is an effective diagnostic tool in evaluating synchronous CRC and RCC. By analyzing this clinical case and conducting bioinformatic analysis, we improved our current understanding of the mechanisms underlying synchronous tumors.

Methods: A total of 19 patients who underwent preoperative spectral CT dual-phase enhancement and who were diagnosed with HCC by postoperative pathology were prospectively selected. Patients with ≥10% Ki67-positive tumor cells formed a high-Ki67 group, and those with <10% Ki67- positive cells formed a low-Ki67 group. The iodine concentrations (ICs) of the lesion and the descending aorta were measured during the arterial and venous phases. Relative iodine concentration (RIC) was calculated thus: RIC=IC_lesion/IC_{descending aorta}. CT values of the lesions at 40 and 70 keV were measured during the enhanced arterial and venous phases. The slope of the spectral curve (λ) was calculated thus: λ = (40 keV-70 keV) /(70-30). To compare the differences in quantitative parameters between the high- and low-Ki67 groups, either an independent samples t-test (normal distribution) or a Mann–Whitney U test (non-normal distribution) was used. Receiver operating characteristic curves were used to evaluate the effectiveness of spectral CT parameters in distinguishing between high-Ki67 and low-Ki67 groups. Pearson correlation analysis was used to evaluate the correlation between spectral CT quantitative parameters and Ki67 expression.

Results: IC, RIC and λ values for the high-Ki67 group in arterial and venous phases were higher than those for the low-Ki67 group, P < 0.05. IC, RIC, and λ values in the arterial phase were 0.83, 0.89, and 0.75, respectively; in the venous phase, the values of these three parameters were 0.76, 0.77, and 0.69, respectively. IC, RIC, and λ were positively correlated with Ki67 expression in both arterial and venous phases, with a highest correlation of 0.82 for arterial-phase RIC.

Conclusion: The quantitative parameters of spectral CT in HCC were correlated with Ki67 expression. This finding may make it easier for clinicians to determine whether a tumor is high or low in Ki67 before surgery.

Objectives: To determine whether DLIR can provide better image quality and reduce radiation dose in contrast-enhanced abdominal CT compared with the second generation of adaptive statistical iterative reconstruction (ASiR-V).

Aims: This study aims to determine whether deep-learning image reconstruction (DLIR) can improve image quality.

Methods: In this retrospective study, a total of 102 patients were included, who underwent abdominal CT using a DLIR-equipped 256-row scanner and routine CT of the same protocol on the same vendor's 64-row scanner within four months. The CT data from the 256-row scanner were reconstructed into ASiR-V with three blending levels (AV30, AV60, and AV100), and DLIR images with three strength levels (DLIR-L, DLIR-M, and DLIR-H). The routine CT data were reconstructed into AV30, AV60, and AV100. The contrast-to-noise ratio (CNR) of the liver, overall image quality, subjective noise, lesion conspicuity, and plasticity in the portal venous phase (PVP) of ASiR-V from both scanners and DLIR were compared.

Results: The mean effective radiation dose of PVP of the 256-row scanner was significantly lower than that of the routine CT (6.3±2.0 mSv vs. 2.4±0.6 mSv; p< 0.001). The mean CNR, image quality, subjective noise, and lesion conspicuity of ASiR-V images of the 256-row scanner were significantly lower than those of ASiR-V images at the same blending factor of routine CT, but significantly improved with DLIR algorithms. DLIR-H showed higher CNR, better image quality, and subjective noise than AV30 from routine CT, whereas plasticity was significantly better for AV30.

Conclusion: DLIR can be used for improving image quality and reducing radiation dose in abdominal CT, compared with ASIR-V.

Methods: After the exclusion of the articles as per the exclusion criteria, the total articles that fulfilled the inclusive criteria were reviewed. In addition, all the articles were further cross-referenced for additional articles. All published papers retrieved from this search were considered for this review. A total of 22 records (26 cases) were found with a diagnosis of LRs in the kidney to date. Some articles were published as case series. Accordingly, 26 patients were reported to have Liesegang rings associated with kidney neoplastic and non-neoplastic conditions, 12 were male and 14 were female. For one case the gender was not mentioned. LRs presented a higher frequency in individuals between 4th and 5th decades of life. No single case was reported in infants and younger children. Regarding predisposing factors for LRs, cystic fluid contents were the most common underlying condition.

Results: In our practice, we encountered an unusual case of a 55-year-old female with a complaint of pain in the left upper quadrant of the abdomen. The ultrasound revealed nephrolithiasis and chronic kidney disease for which a nephrectomy was performed. On the histopathological examination, there was an incidental finding of Liesegang rings and a papillary adenoma along with features of chronic pyelonephritis. Our review will provide insight about LRs in different spectrums of kidney diseases.

Conclusion: This study represents the first available systematic review of the literature demonstrating LRs in the kidney. Although Liesegang rings have no great clinical significance, these, presence in both tissue and cytological specimens should be kept in mind while dealing with different lesions of the kidney as these are good mimickers of many organic and inorganic substances, parasites, and malignancies.

Aim: In the present study, we aimed to compare sonoelastographic changes in both kidneys between patients who had totally recovered from COVID-19 and healthy individuals using strain wave elastography (SWE).

Methods: This study was conducted between June 2021 and May 2022 in Kahramanmaraş City Hospital Department of Radiology. File and archive records were retrospectively evaluated. Basic demographic, laboratory, and renal ultrasonography (USG) and sonoelastographic findings were screened and noted. Two groups were defined to compare sonoelastographic findings. Post-/long-COVID-19 group had 92 post-long COVID-19 patients, and the comparator group comprised healthy individuals”. Both groups’ demographic, laboratory, and ultrasound-elastographic findings were assessed.

Results: The post-long COVID-19 group had a higher renal elastographic value than the comparator group (1.52 [0.77–2.3] vs. 0.96 [0.54–1.54], p<0.001). There were no statistically significant differences between the two groups in terms of age (p=0.063), gender (p=0.654), or body mass index (BMI) (p=0.725), however, there was a significant difference observed between the two groups in the renal strain ratio (RSR). According to an receiver operating characteristic curve (ROC) analysis, an RSR cutoff of >1.66 predicted post-long COVID-19 with 44.9% sensitivity and 81.9% specificity. (AUC=0.655, p<0.001). A separate ROC analysis was performed to predict post-long COVID-19 with a BMI cutoff of <33.52, kg/m2 sensitivity of 92.4% and specificity of 17% (AUC=0.655, p<0.001).

Conclusion: We demonstrated that renal parenchymal stiffness increases with SWE in post-long COVID-19 patients.]]> https://www.benthamscience.comarticle/138776Objective: To investigate the feasibility of image characteristics and radiomics combined with machine learning based on Gd-EOB-DTPA-enhanced MRI for functional liver reserve assessment in cirrhotic patients.

Materials and Methods 123 patients with cirrhosis were retrospectively analyzed; all our patients underwent pre-contrast MRI, triphasic (arterial phase, venous phase, equilibrium phase) Gd-EOB-DTPA dynamic enhancement and hepatobiliary phase (20 minutes delayed). The relative enhancement (RE) of the patient's liver, the liver-spleen signal ratio in the hepatobiliary phase (SI liver/ spleen), the liver-vertical muscle signal ratio in the hepatobiliary phase (SI liver/ muscle), the bile duct signal intensity contrast ratio (SIR), and the radiomics features were evaluated. The support vector machine (SVM) was used as the core of machine learning to construct the liver function classification model using image and radiomics characteristics, respectively.

Results: The area under the curve was the largest in SIR to identify Child-Pugh group A versus Child-Pugh group B+C in the image characteristics, AUC = 0.740, and Perc. 10% to identify Child-Pugh group A versus Child-Pugh group B+C in the radiomics characteristics, AUC = 0.9337. The efficacy of the SVM model constructed using radiomics characteristics was better, with an area under the curve of 0.918, a sensitivity of 95.45%, a specificity of 80.00%, and an accuracy of 89.19%.

Conclusion: The image and radiomics characteristics based on Gd-EOB-DTPA-enhanced MRI can reflect liver function, and the model constructed based on radiomics characteristics combined with machine learning methods can better assess functional liver reserve.

Methods: Forty rabbits with implanted VX2 liver tumors underwent baseline MRI and were then given 10 mg/kg CA4P (n=20) or saline (n=20). After 4 h, 10 rabbits from each group underwent an MRI examination and were then sacrificed. The remaining rabbits underwent MRI after 1, 3, and 7 days and were then sacrificed. Liver samples were processed for H&E and immunohistochemical staining. IVIM parameters (D, f, D*) were compared in the treatment and control groups, and the correlations of IVIM parameters with microvascular density (MVD) were determined.

Results: At 4 h, the two treatment groups had significantly different f and D* values (p<0.001), and these values were at their minimum in the treatment group. The treatment group had moderate correlations between MVD and f at 4 h (r=0.676, p=0.032) and 7 days (r=0.656, p=0.039) and with D* at 4 h (r=0.732, p=0.016) and 7 days (r=0.748, p=0.013), but no correlation was reported between MVD and f or D* in the control group (all P>0.05).

Conclusion: IVIM DW-MRI is a sensitive imaging technique. It successfully evaluated the effect of CA4P on VX2 liver tumors in rabbits. The f and D* values correlated with MVD at 4 h and 7 days after using CA4P, indicating that these parameters have the potential to be used as indicators of tumor angiogenesis after treatment.

Methods: We synthesized EF-AuNps using a direct reduction method and characterized the NPs by employing various techniques, including UV-visible spectroscopy, DLS, XRD, EDX, TEM, and FT-IR. The anti-proliferative activity against MDA-MB-231 cells was assessed using MTT and colony formation assays, alongside evaluating cell viability with PI-FACS and live/dead assays. Furthermore, a Western blot was performed to determine the mechanism of action of EFAuNps in TNBC cells.

Result: We successfully synthesized triangular EF-AuNps (<100nm) and observed a substantial inhibition of cell proliferation (IC₅₀ 18μg/ml). Compared to EF alone, EF-AuNps significantly enhanced cell death in TNBC cells, as confirmed by flow cytometry and viability assays. Besides, Western blot analysis verified that the expression of apoptotic-related signal proteins, such as survivin, caspase 3, and caspase 9, were modulated by EF-AuNps.

Conclusion: EF-AuNps showed higher anti-cancer efficacy than EF in the MDA-MB-231 cell line. These findings suggest the therapeutic potential of EF-AuNps for TNBC treatment, advocating for further preclinical and clinical investigations into this promising anti-cancer formulation.

Case Presentation: Herein, we report the case of a 55-year-old woman with breast cancer. She previously underwent extensive excision of the breast lesion with adjuvant chemotherapy and endocrine therapy. After 9 years, she presented with neck discomfort and examination suggested right thyroid metastasis and lymph node metastasis in the neck. Imaging showed pulmonary and bone metastases. Furthermore, the patient received endocrine therapy. After 7 months of follow- up, the patient survived without any new distant metastases. Thyroid metastases originating from breast cancer often unfold with a subtle, intricate nature, making early detection challenging. They tend to emerge inconspicuously, intertwining with widespread systemic metastases, hinting at a less favorable prognosis.

Conclusion: Given the unusual clinical indicators, identifying heterochronic thyroid metastases in patients with tumors poses a distinct challenge, requiring clinicians to navigate the follow-up process with heightened sensitivity. The key lies in timely detection and early intervention, factors that can significantly enhance the overall quality of life for patients.

Objective: This study aimed to review the possible effects of Per and poly-fluoroalkyl substances exposure and their mechanism in overweight/obese children from pregnant ladies.

Methods: A detailed literature survey was conducted using online databases, including Science Direct, Google Scholar, Scopus, Cochrane, and PubMed. The study focused on the diverse effects of PFAS on maternal and child health, with particular emphasis on neurological complications.

Results: Child growth development depends upon breastfeeding and placenta health, which is disrupted by PFAS exposure, ultimately destroying the body mass index of the child. Neurotoxicity testing utilized the SH-SY5Y human-derived cell line as an in vitro model, revealing PFAS-induced increases in adipocyte number, reduced cell size, altered lipid conglomeration, increased adiposity, and changes in liver function. in vivo studies in mice and human cell lines indicated PPAR-γ and ER-α activation, leading to adiposity and weight gain through Estrogen signaling and Lipid metabolism. PFAS concentrations positively correlated in maternal sera, analyzed by liquid chromatography/quadrupole mass spectrometry.

Conclusion: PFAS, with a long half-life of 3.5-8.5 years, is commonly found in the serum of pregnant women, crossing the placenta barrier. This exposure disrupts placental homeostasis, negatively impacting mechanisms of action and potentially leading to deterioration in pregnancy and child health. Further research is needed to comprehensively understand the complex interplay between PFAS exposure and its implications for maternal and child well-being.

Methods: Rat renal proximal tubule NRK-52E cells were treated with different concentrations of DFO for 24 hours, followed by evaluation of RTEC injury, using a Cell Counting Kit-8 (CCK-8) to detect cell viability and western blotting to evaluate the expression of transforming growth factor- beta 1 (TGF-β1), α-smooth muscle actin (α-SMA), and hypoxia-inducible factor-1 alpha (HIF-1α) in NRK-52E cells. Then, three groups of NRK-52E cells were used in experiments, including normal control (NC), 25 μM DFO, and 25 μM DFO + MSC-CM. MSC-CM was obtained from the human umbilical cord. MSC-CM was used to culture cells for 12 hours before DFO treatment, then fresh MSC-CM and 25 μM DFO were added, and cells were cultured for another 24 hours before analysis.

Results: Western blotting and cellular immunofluorescence staining showed culture of NRK-52E cells in 25 μM DFO for 24 hours induced HIF-1α and nuclear receptor coactivator-1 (NCoA-1), simulating hypoxia. MSC-CM could inhibit the DFO-induced up-regulation of α-SMA, TGF-β1, HIF-1α and NCoA-1.

Conclusion: Our results suggest that MSC-CM has a protective effect on RTECs by down-regulating HIF-1α and NCoA-1, which may be the harmful factors in renal injury.

Methods: To ensure a thorough search of the literature for relevant English studies published before July 2023, several databases were searched, including PubMed, Web of Science, ProQuest, Cochrane Library, and Google Scholar. The study evaluated the impact of lncRNA SNHG5 on the overall survival (OS) of cancer by calculating the pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence intervals (CIs). To further confirm the accuracy of the findings, the study investigated the expression profile and prognostic significance of lncRNA SNHG5 through the use of GenomicScape, OncoLnc, Kaplan-Meier plotter, and GEPIA databases.

Results: In this study, 995 patients were examined across a total of fourteen original studies. The findings indicated that there was a significant relationship between heightened lncRNA SNHG5 expression and reduced OS, as evidenced by both univariate and multivariate analyses (HR = 1.89; 95% CI, 1.44-2.49; p < 0.001; HR = 3.97; 95% CI, 1.80-8.73; p < 0.001, respectively). Pooled OR analysis showed a significant association between over-expression of lncRNA SNHG5 with advanced histological grade (OR = 0.28; 95% CI, 0.11-0.71; p = 0.007), present lymph node metastasis (LNM; OR = 4.28; 95% CI, 2.47-7.43; p < 0.001), and smoking history (OR = 0.27; 95% CI, 0.15-0.49; p < 0.001). Bioinformatic databases confirmed that elevated SNHG5 expression was significantly linked to poor prognosis in cancer patients, including colorectal cancer (CRC), acute myeloid leukemia (AML), and esophageal adenocarcinoma (ESAD), and a longer OS in patients with uterine corpus endometrial carcinoma (UCEC).

Conclusion: These results suggest that lncRNA SNHG5 may serve as an adverse prognostic biomarker in several human cancers. Further investigations are needed to better understand the underlying mechanisms that link lncRNA SNHG5 to multiple malignancies.

Methods: Expression of NEIL3 and its upstream transcription factor MAZ in HCC tumor tissues was analyzed in bioinformatics efforts, while validation was done by qRT-PCR and western blot in HCC cell lines. The migration and tube formation capacity of HUVEC cells were analyzed by Transwell and tube formation assays. Glycolytic capacity was analyzed by extracellular acidification rate, glucose uptake, and lactate production levels. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter gene assays were utilized to investigate specific interactions between MAZ and NEIL3.

Results: NEIL3 and MAZ were substantially upregulated in HCC tissues and cells. NEIL3 was involved in modulating the glycolysis pathway, suppression of which reversed the stimulative impact of NEIL3 overexpression on migration and angiogenesis in HUVEC cells. MAZ bound to the promoter of NEIL3 to facilitate NEIL3 transcription. Silencing MAZ reduced NEIL3 expression and suppressed the glycolysis pathway, HUVEC cell migration, and angiogenesis.

Conclusion: MAZ potentiated the upregulated NEIL3-mediated glycolysis pathway and HCC angiogenesis. This study provided a rationale for the MAZ/NEIL3/glycolysis pathway as a possible option for anti-angiogenesis therapy in HCC.

Aims: The results are desired to provide an important theoretical basis for discovering new therapeutic targets for CRC.

Objectives: The expression of human endogenous retrovirus-H-long terminal repeat association protein 2 (HHLA2) in human CRC was detected to explore its correlationship with clinicopathological features and prognosis of patients and its potential in treating CRC.

Methods: Western blot was employed to detect HHLA2 expression in fresh tissues obtained from 6 CRC patients' excisions, including cancer, paracancer, and normal issues. Immunohistochemical staining was employed to determine HHLA2 expression in paraffin-embedded specimens of 139 patients with colorectal cancer, and its relationship with the clinicopathological profiles and survival was analyzed. Small interfering RNA (siRNA) targeting HHLA2 was used to transfect CRC cells to silent HHLA2. MTT, plate colony formation, cell scratch, and Transwell assay were conducted to observe the proliferation, migration, and invasion of CRC cells.

Results: HHLA2 protein was expressed in human colorectal cancer tissues, paracancer tissues and normal tissues, which was significantly upregulated in cancer tissues (P < 0.01). HHLA2 expression level in CRC tissues showed a close correlationship with the invasion depth of the tumor (P = 0.000), metastasis of regional lymph nodes (P = 0.018), clinical stage (P = 0.010), and patient survival (P = 0.011). Correlation with gender (P = 0.873), age (P = 0.864), location of the tumor (P = 0.768), degree of tumor differentiation (P = 0.569) and distant metastasis (P = 0.494) exhibited no significance. The survival time of CRC patients with high and low HHLA2 expression groups was 43.231 months and 55.649 months, respectively, with a statistical difference between the two groups (P = 0.001). Silencing HHLA2 inhibited proliferation, migration and invasion of CRC cells significantly.

Conclusion: HHLA2 is overexpressed in CRC tissues which is associated with poor prognosis of patients. HHLA2 might be recognized as a new candidate for adjuvant diagnosis and prognosis of CRC, as well as a promised new target for immunotherapy of CRC.

Methods: We performed in vitro gene silencing, cytotoxicity, and agarose gel electrophoresis to identify the optimal GLPS formulation. In vitro MRI and Prussian blue staining verified the liver-targeting function of GLPS. We also analyzed the biocompatibility of GLPS by co-culturing with rabbit red blood cells. Morphological changes were evaluated using HE staining.

Results: The GLPS optimal formulation consisted of LPS and siRNA at a mass ratio of 25:1 and LPS and DSPE-PEG-GPC3 at a molar ratio of 2:3. GLPS exhibited evident liver-targeting function. In vitro, we did not observe morphological changes in red blood cells or hemolysis after co-culture. In vivo, routine blood analysis revealed no abnormalities after GLPS injection. Moreover, the tissue morphology of the kidney, spleen, and liver was normal without injury or inflammation.

Conclusion: GLPS could potentially serve as an effective carrier for liver-targeted MRI monitoring and siRNA delivery.

Methods: We conducted a comprehensive analysis of the expression of SLC7A11 across 33 cancer types, employing datasets from public databases. Methods, such as Cox regression and survival analyses assessed its prognostic significance, while functional enrichment explored the biological processes tied to SLC7A11. The association between SLC7A11 expression, immune cell infiltration, and immune-related gene expression was also scrutinized.

Results: Notably, SLC7A11 expression was more pronounced in cancerous compared to normal samples and correlated with higher tumor grades. Increased SLC7A11 expression was linked to poor outcomes, particularly in liver hepatocellular carcinoma (LIHC). This protein's expression also showcased significant relationships with diverse molecular and immune subtypes.

Additionally, a prognostic nomogram was devised, integrating SLC7A11 expression and clinical variables. High SLC7A11 levels corresponded with cell growth and senescence pathways in various cancers and with lipid and cholesterol metabolism in LIHC. Furthermore, potential therapeutic compounds for LIHC with high SLC7A11 were identified. Real-time PCR (qPCR) and Western blot were conducted to explore the expression of SLC7A11 in tumor tissues and cancer cell lines.

Conclusion: In summation, this study emphasizes the prognostic and immunological importance of SLC7A11, spotlighting its potential as a therapeutic target in LIHC.

Objectives: The present study evaluated the pharmacokinetics and safety of Prusogliptin in subjects with mild or moderate hepatic impairment compared with healthy subjects.

Methods: According to the liver function of the subjects, we divided them into a mild liver dysfunction group, a moderate liver dysfunction group and a normal liver function group. All subjects in three groups received a single oral dose of Prusogliptin 100-mg tablets. Pharmacokinetics and safety index collection was carried out before and after taking the drug. Plasma pharmacokinetics of Prusogliptin were evaluated, and geometric least- -squares mean (GLSM) and associated 90% confidence intervals for insufficient groups versus the control group were calculated for plasma exposures.

Results: After a single oral administration of 100 mg of Prusogliptin tablets, the exposure level of Prusogliptin in subjects with mild liver dysfunction was slightly higher than that in healthy subjects. The exposure level of Prusogliptin was significantly increased in subjects with moderate liver dysfunction. There were no adverse events in this study.

Conclusion: The exposure level of Prusogliptin in subjects with liver dysfunction was higher than that in healthy subjects. No participant was observed of adverse events. Prusogliptin tablets were safe and well tolerated in Chinese subjects with mild to moderate liver dysfunction and normal liver function.

Objective: To design a single automated radiolabeling protocol for the GMP-compliant preparation of [⁶⁸Ga]Ga-PSMA-11, transposable to the production of [⁶⁸Ga]Ga-PSMA-617 and [⁶⁸Ga]Ga-PSMA-I&T.

Methods: A GAIA^® synthesis module and a GALLIAD^® generator were used. Radio-TLC and radio-HPLC methods were validated for radiochemical purity (RCP) determination. Three [⁶⁸Ga]Ga-PSMA-11 validation batches were produced and thoroughly tested for appearance and pH, radionuclide identity and purity, RCP, stability, residual solvent and sterility. Minimal modifications were made to the reagents and disposables for optimal application to other PSMA ligands.

Results: [⁶⁸Ga]Ga-PSMA-11 for clinical application was produced in 27 min. The 3 validation batches met the quality criteria expected by the European Pharmacopoeia to allow routine production. For optimal transposition to PSMA-617, the solid phase extraction cartridge was changed to improve purification of the radiolabeled product. For application to PSMA-I&T, the buffer solution initially used was replaced by HEPES 2.7 M to achieve good radiochemical yields. Residual HEPES content was checked in the final product and was below the Ph. Eur. threshold.

Conclusion: A single automated radiolabeling method on the GAIA^® module was developed and implemented for ⁶⁸Ga radiolabeling of 3 PSMA ligands, with slight adjustments for each molecule.

Methods: Raw data from microarray chips with GEO accession GSE49541 were downloaded from the Gene Expression Omnibus database, and the R package (Affy and Limma) was applied to investigate differentially expressed genes (DEGs) involved in the progress of low- (mild 0-1 fibrosis score) to high- (severe 3-4 fibrosis score) fibrosis stage NAFLD patients. Subsequently, significant DEGs with pathway enrichment were analyzed, including gene ontology (GO), KEGG and Wikipathway. In order to then explore critical genes, the protein-protein interaction network (PPI) was established and visualized using the STRING database, with further analysis undertaken using Cytoscape and Gephi software. Survival analysis was undertaken to determine the overall survival of the hub genes in the progression of NAFLD to hepatocellular carcinoma.

Results: A total of 311 significant genes were identified, with an expression of 278 being upregulated and 33 downregulated in the high vs. low group. Gene functional enrichment analysis of these significant genes demonstrated major involvement in extracellular matrix (ECM)-receptor interaction, protein digestion and absorption, and the AGE-RAGE signaling pathway. The PPI network was constructed with 196 nodes and 572 edges with PPI enrichment using a p-value < 1.0 e-16. Based on this cut-off, we identified 12 genes with the highest score in four centralities: Degree, Betweenness, Closeness, and Eigenvector. Those twelve hub genes were CD34, THY1, CFTR, COL3A1, COL1A1, COL1A2, SPP1, THBS1, THBS2, LUM, VCAN, and VWF. Four of these hub genes, namely CD34, VWF, SPP1, and VCAN, showed significant association with the development of hepatocellular carcinoma.

Conclusion: This PPI network analysis of DEGs identified critical hub genes involved in the progression of fibrosis and the biological pathways through which they exert their effects in NAFLD patients. Those 12 genes offer an excellent opportunity for further focused research to determine potential targets for therapeutic applications.

Methods: Based on the PRISMA guideline, we performed a systematic search for the identification of all relevant studies in various electronic databases up to June 2022. According to the inclusion and exclusion criteria, the obtained articles (n=59) were screened and 13 eligible articles were finally included in the present study.

Results: The findings of in-vitro experiments showed that cisplatin treatment significantly reduced the auditory cell viability in comparison with the control group; nevertheless, the alpha-lipoic acid co-administration protected the cells against the reduction of cell viability induced by cisplatin treatment. Moreover, the in-vivo results of the auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) tests revealed a decrease in DPOAE and an increase in ABR threshold of cisplatin-injected animals; however, it was shown that alpha-lipoic acid co-treatment had an opposite pattern on the evaluated parameters. Other findings demonstrated that cisplatin treatment could significantly induce the biochemical and histopathological alterations in inner ear cells/tissue; in contrast, alpha-lipoic acid co-treatment ameliorated the cisplatin-mediated biochemical and histological changes.

Conclusion: The findings of audiometry, biochemical parameters, and histological evaluation showed that alpha-lipoic acid co-administration alleviates the cisplatin-induced ototoxicity. The protective role of alpha-lipoic acid against the cisplatin-induced ototoxicity can be due to different mechanisms of anti-oxidant, anti-apoptotic, anti-inflammatory activities, and regulation of cell cycle progression.

Objective: To understand the immunomodulatory properties of various phytochemicals and investigate them in Echinacea species extracts using an in silico approach.

Methodology: Several scientific database repositories were searched using different keywords: “Phytochemicals,” “Alkaloids,” “Polyphenols,” “Flavonoids,” “Lectins,” “Glycosides,” “Tannins,” “Terpenoids,” “Sterols,” “Immunomodulators,” and “Human Immune System” without any language restriction. Additionally, the study specifically investigated the immunomodulatory properties of Echinacea species extracts using gene expression analysis of GSE12259 from NCBI-GEO through the Bioconductor package GEOquery and limma.

Results: A total of 182 studies were comprehensively analyzed to understand immunomodulatory phytochemicals. The in silico analysis highlighted key biological processes (positive regulation of cytokine production, response to tumor necrosis factor) and molecular functions (cytokine receptor binding, receptor-ligand activity, and cytokine activity) among Echinacea species extracts contributing to immune responses. Further, it also indicated the association of various metabolic pathways, i.e., pathways in cancer, cytokine-cytokine receptor interaction, NF-kappa B, PI3K-Akt, TNF, MAPK, and NOD-like receptor signaling pathways, with immune responses. The study revealed various hub targets, including CCL20, CCL4, GCH1, SLC7A11, SOD2, EPB41L3, TNFAIP6, GCLM, EGR1, and FOS.

Conclusion: The present study presents a cumulative picture of phytochemicals with therapeutic benefits. Additionally, the study also reported a few novel genes and pathways in Echinacea extracts by re-analyzing GSE 12259 indicating its anti-inflammatory, anti-viral, and immunomodulatory properties.

Aim: To clarify the mechanism of HDW for esophageal adenocarcinoma (EAC), we utilized network pharmacology and weighted gene co-expression network analysis methods (WGCNA).

Methods: The gene modules that were linked with the clinical features of EAC were obtained through the WGCNA method. Then, the potential target genes were retrieved through the network pharmacology method in order to determine the targets of the active components. After enrichment analysis, a variety of signaling pathways with significant ratios of target genes were found, including regulation of trans-synaptic signaling, neuroactive ligand-receptor interaction and modulation of chemical synaptic transmission. By means of protein-protein interaction (PPI) network analysis, we have successfully identified the hub genes, which were AR, CNR1, GRIK1, MAPK10, MAPT, PGR and PIK3R1.

Result: Our study employed molecular docking simulations to evaluate the binding affinity of the active components with the hub gene. The identified active anticancer constituents in HDW are scopoletol, quercetin, ferulic acid, coumarin, and trans-4-methoxycinnamyl alcohol.

Conclusion: Our findings shed light on the molecular underpinnings of HDW in the treatment of EAC and hold great promise for the identification of potential HDW compounds and biomarkers for EAC therapy.

Objective: The present study aims to enhance understanding of the disease mechanism and its progression by identifying prognostic biomarkers, potential drug targets, and candidate drugs that can be used for therapy in pancreatic cancer.

Methods: Gene expression profiles from the GEO database were analyzed to identify reliable prognostic markers and potential drug targets. The disease's molecular mechanism and biological pathways were studied by investigating gene ontologies, KEGG pathways, and survival analysis to understand the strong prognostic power of key DEGs. FDA-approved anti-cancer drugs were screened through cell line databases, and docking studies were performed to identify drugs with high affinity for ARNTL2 and PIK3C2A. Molecular dynamic simulations of drug targets ARNTL2 and PIK3C2A in their native state and complex with nilotinib were carried out for 100 ns to validate their therapeutic potential in PDAC.

Results: Differentially expressed genes that are crucial regulators, including SUN1, PSMG3, PIK3C2A, SCRN1, and TRIAP1, were identified. Nilotinib as a candidate drug was screened using sensitivity analysis on CCLE and GDSC pancreatic cancer cell lines. Molecular dynamics simulations revealed the underlying mechanism of the binding of nilotinib with ARNTL2 and PIK3C2A and the dynamic perturbations. It validated nilotinib as a promising drug for pancreatic cancer.

Conclusion: This study accounts for prognostic markers, drug targets, and repurposed anti-cancer drugs to highlight their usefulness for translational research on developing novel therapies. Our results revealed potential and prospective clinical applications in drug targets ARNTL2, EGFR, and PI3KC2A for pancreatic cancer therapy.

Methods: The online STRING web source was used to construct a protein network interacting with ETS1. The Cell Counting Kit-8 was used to detect the cell viability. A clonogenic assay, a wound-healing assay, and a Transwell assay were used to detect cell proliferation, invasion and migration abilities. Western blot was used to detect the expression of proteins.

Results: The data showed the expression of ETS1 in ccRCC tissues to be significantly increased compared to adjacent tissues (p<0.05). The positive expression of ETS1 in ccRCC patients aged 20–100 was statistically significant compared to adjacent normal tissues (p<0.05). The grade of ETS1 positive expression (1-4) and lymph node metastasis (N1) in ccRCC were significantly higher than those in adjacent normal tissues (p<0.05). The tumour stage (stages 1-4) in ccRCC patients with positive ETS1 expression was significantly higher than that in adjacent normal tissues (p<0.05). Knockdown of ETS1 and PERK inhibitors significantly inhibited the proliferation, migration and invasion of ccRCC cells. Knockdown of ETS1 inhibited MMP-2 expression, and an extracellular signal-related kinase (ERK) inhibitor inhibited both ETS1 and MMP-2 expression.

Conclusion: A high expression of ETS1 is associated with the progression of ccRCC. This study suggests that ETS1 promotes proliferation by increasing MMP2 expression in ccRCC, and combined knockdown of ETS1 and inhibition of ERK can significantly inhibit the proliferation, migration and invasion of ccRCC. ETS1 may be a therapeutic and prognostic target for renal cell carcinoma.

Materials and Methods: A mutator hypothesis was employed, combining the TCGA database of somatic mutation (SM) information, to identify GI-lncRNAs. Subsequently, a training cohort (n = 442) and a testing cohort (n = 439) were formed by randomly dividing all RCC patients. Based on the training cohort dataset, a multivariate Cox regression analysis lncRNAs risk model was created. Further validations were performed in the testing cohort, TCGA cohort, and different RCC subtypes. To confirm the relative expression levels of lncRNAs in HK-2, 786-O, and 769-P cells, qPCR was carried out. Functional pathway enrichment analyses were performed for further investigation.

Results: A total of 170 novel GI-lncRNAs were identified. The lncRNA prognostic risk model was constructed based on LINC00460, AC073218.1, AC010789.1, and COLCA1. This risk model successfully differentiated patients into distinct risk groups with significantly different clinical outcomes. The model was further validated in multiple independent patient cohorts. Additionally, functional and pathway enrichment analyses revealed that GI-lncRNAs play a crucial role in GI. Furthermore, the assessments of immune response, drug sensitivity, and cancer stemness revealed a significant relationship between GI-lncRNAs and tumor microenvironment infiltration, mutational burden, microsatellite instability, and drug resistance.

Conclusions: In this study, we discovered four novel GI-lncRNAs and developed a novel signature that effectively predicted clinical outcomes in pan-RCC. The findings provide valuable insights for pan-RCC immunotherapy and shed light on potential underlying mechanisms.

Introduction: Early evaluation of the safety of 1 was conducted in cynomolgus monkeys in which oral doses were administered to three animals in a rising-dose fashion (from 2 to 30 mg/kg/day). 1 produced severe toxicity including the evidence of hepatic toxicity, along with non-dose proportional increases in drug exposure. Investigations of cross-species hepatic bioactivation of 1 were conducted to assess whether the formation of reactive drug metabolites was associated with the mechanism of liver toxicity.

Methods: 1 contained two morpholine rings known as structural alerts and can potentially form reactive intermediates through oxidative metabolism. Bioactivation of 1 was investigated in rat, human and monkey liver microsomes fortified with trapping agents such as methoxylamine or potassium cyanide.

Results: Our results suggest that bioactivation of the morpholine moieties to reactive intermediates may have been involved in the mechanism of liver toxicity observed with 1. Aldehyde intermediates trappable by methoxylamine were identified in rat and monkey liver microsomal studies. In addition, a total of four cyano conjugates arising from the formation of iminium ion intermediates were observed and identified. These findings may potentially explain the observed monkey toxicity. Interestingly, methoxylamine or cyano adducts of 1 were not observed in human liver microsomes.

Conclusion: The bioactivation of 1 appears to be species-specific. Circumstantial evidence for the toxicity derived from 1 point to the formation of iminium ion intermediates trappable by cyanide in monkey liver microsomes. The cyano conjugates were only observed in monkey liver microsomes, potentially pointing to cause at least the hepatotoxicity observed in monkeys. In contrast, methoxylamine conjugates were detected in both rat and monkey liver microsomes, with only a trace amount in human liver microsomes. Cyano conjugates were not observed in human liver microsomes, challenging the team on the drugability and progressivity of 1 through drug development. The mechanisms for drug-induced liver toxicity are multifactorial. These results are highly suggestive that the iminium ion may be an important component in the mechanism of liver toxicity 1 observed in the monkey.

Methods: Bioinformatics analyses were employed to clarify TRIP13 expression in CRC tissues and predict the correlation of the TRIP13 enrichment pathway with glycolysis-related genes and stemness index mRNAsi. Quantitative real-time polymerase chain reaction and western blot were adopted to analyze the expression of TRIP13 and glycolysis- related genes. Cell Counting Kit-8 was utilized to determine the cell viability and IC₅₀ value. Western blot was employed to measure the expression of stemness-related factors. Cell function assays were performed to detect cells' sphere-forming ability and glycolysis level. Animal models were constructed to determine the effects of TRIP13 expression on CRC tumor growth.

Results: TRIP13 was significantly overexpressed in CRC, concentrated in the glycolysis signaling pathway, and positively correlated with stemness index mRNAsi. High expression of TRIP13 facilitated DOX resistance in CRC. Further mechanistic studies revealed that overexpression of TRIP13 could promote cell stemness through glycolysis, which was also confirmed in animal experiments.

Conclusion: TRIP13 was highly expressed in CRC, which enhanced the DOX resistance of CRC cells by activating glycolysis to promote cell stemness. These findings offer new insights into the pathogenesis of DOX resistance in CRC and suggest that TRIP13 may be a new target for reversing DOX resistance in CRC.