Materials and Methods: Twenty-two studies were included, describing 24 models characterized by substantial heterogeneity in terms of study populations, methodological design, and covariate selection. Most models were developed in Asia and focused on hospitalized patients, particularly those in intensive care units (ICUs). Data from 2150 patients were analyzed, with an average of 93 patients per model.

Results: The models demonstrated high variability in pharmacokinetic parameters, such as vancomycin clearance (Cl) and volume of distribution (Vd), influenced by factors, such as renal function, weight, age, and comorbidities. The meta-analysis conducted on clearance and interindividual variability in clearance (IIV Cl) revealed high heterogeneity among the analyzed studies. The average vancomycin clearance was 4.23 L/h, with higher values observed in neurosurgical, oncohematologic patients, and those with increased renal function. The volume of distribution showed greater variability in obese patients and those undergoing continuous renal replacement therapy. Creatinine clearance (ClCr) was identified as a significant covariate in 66% of the models, while weight was significant in 33%. Other important covariates included age, sex, serum creatinine, serum urea, and the hospital admission unit. The metaanalysis of Cl and IIV Cl showed high heterogeneity among the studies, with I² values of 0.83 for Cl and 0.98 for IIV Cl, indicating substantial variability.

Discussion: The limitations of this study included the diversity of the analyzed populations, which made it challenging to assess the model's suitability. While the models showed advances in precision, challenges, such as the lack of external validation and discrepancies in dosing recommendations, remain.

Conclusion: This review paper has highlighted the need to validate models in diverse populations and clinical settings to optimize personalized vancomycin therapy in adults. The findings have highlighted the importance of validating or adapting pharmacokinetic models to the specific characteristics of each hospital population.

Methods: The pharmacokinetics of MA-CEP-PMs in rats were assessed using Ultra-Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometry (UPLC-Q-TOF-MS). Lung-targeting ability was evaluated through tissue distribution studies and near-infrared imaging. In a rat model of ALI induced by lipopolysaccharide (LPS), anti-ALI effects were assessed via general physiological indicators, Enzyme-Linked Immunosorbent Assay (ELISA), and Western blot analysis. Hematoxylin-eosin (HE) staining was used to examine hepatotoxicity and nephrotoxicity of MA-CEP-PMs in normal rats. Cytotoxicity of the mannosylated polyethylene glycol–poly(lactic-co-glycolic acid) copolymer (MA-PEGPLGA) on NR8383 cells was evaluated using the Cell Counting Kit-8 (CCK-8) assay. Cellular uptake experiments were performed to determine the targeting ability of MA-PEG-PLGA in NR8383 cells, and the effects of MA-CEP-PMs on inflammatory cytokines were analyzed using ELISA.

Results: MA-CEP-PMs significantly increased the AUC and exhibited better lung targeting ability compared to the unmodified micelles (p < 0.01). In the ALI model, MA-CEP-PMs improved the thymus and spleen indices, decreased the lung wet-to-dry weight ratio (p < 0.05), alleviated model animal damage, and inhibited inflammatory factor and nuclear factor-κB (NF-κB)–related protein levels (p < 0.05). MACEP- PMs exhibited no significant hepatotoxicity or nephrotoxicity. MA-PEG-PLGA exhibited low toxicity against NR8383 cells and greater cell uptake, indicating stronger targeting of the lung. MA-CEPPMs also exhibited more potent anti-inflammatory effects.

Discussion: This study focused on the short-term therapeutic effects of ALI, whereas the clinical management of lung injury often requires long-term intervention. Future research should therefore assess the long-term efficacy of this delivery system in chronic lung injury, along with determining its safety profile and potential impacts on extra-pulmonary organs. While the involvement of the NF-κB pathway in the anti-inflammatory effects has been confirmed, it remains to be deciphered whether mannose modification synergistically regulates other signaling pathways and what the specific intracellular targets of CEP are, which would require further exploration through detailed molecular biology experiments.

Conclusion: The MA-CEP-PMs significantly improved CEP bioavailability and increased lung targeting. They exhibited good safety and had a significant effect on ALI management.

Methods: The cerebral ischemia-reperfusion injury (CIRI) model was established by middle cerebral artery occlusion (MCAO). The therapeutic effect of Ai pian on CIRI rats was evaluated by behavioral test, 2,3,5-triphenyltetrazolium chloride (TTC) staining, Nissl staining, and hematoxylin-eosin (HE) staining. The active compound–potential target–disease network for Ai Pian in the treatment of CIRI was established using network pharmacology methods. Rat serum was detected by the metabolomics technique based on UPLC-MS. A Western blot was used to validate common targets of the network pharmacology approach combined with serum metabolomics.

Results: The process of treating CIRI with Ai Pian involved regulating enzyme, nuclear receptor, and transcription factor activity, managing the inflammatory response, and participating in biofilm composition. Twenty endogenous potential biomarkers were screened and submitted to MetaboAnalyst 6.0 for pathway and enrichment analysis. Four metabolic pathways were identified: butanoate metabolism, fructose and mannose metabolism, alanine, aspartate, and glutamate metabolism, and pyrimidine metabolism. Fructose and mannose metabolism and pyrimidine metabolism were two key pathways. Western blot analysis suggested that DHODH, TYMS, and AKR1B1 may be targets through which therapeutic effects are exerted.

Discussion: The present study made preliminary predictions on the possible mechanisms of Ai Pian against CIRI. Differential metabolites were screened and identified, and the relevant metabolic pathways potentially affected by Ai Pian were discovered to understand the importance of these markers in health and disease. However, there were also some limitations, further exploration of the molecular mechanisms at the transcriptional level was necessary to make the experimental results more reliable.

Conclusion: This research contributed to the development of Ai pian as an adjunctive drug for treating CIRI and provided a basis for further research on CIRI.