浙江中医药大学

Orthopaedic infections are increasingly prevalent in the aging population, posing a significant clinical and economic burden. Despite progress in antimicrobial therapies, challenges such as antibiotic resistance and superbug emergence persist. Gas therapy has emerged as a promising strategy for managing orthopaedic infections. Classical gasotransmitters—including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H2S)—exhibit antibacterial and immunomodulatory effects at controlled concentrations, though improper dosing may induce adverse effects. This review critically examines the dual mechanisms through which gasotransmitters combat infection while promoting orthopaedic regeneration. We also survey advanced delivery platforms—such as smart scaffolds, nano-reservoirs, and on-demand release systems—engineered for targeted gasotransmitter delivery to infected bone tissue. Finally, we discuss current limitations and future prospects, aiming to inspire novel biomaterial designs for targeted therapeutic delivery and to advance gas therapy as a viable option for orthopaedic infection treatment.

Pediatric acute kidney injury (AKI) often presents insidiously and progresses rapidly. Traditional diagnostic criteria based on serum creatinine and urine output are markedly delayed and insufficient to capture injury patterns across different etiologies. This paper aims to summarize recent advances in pediatric AKI biomarker research since the release of the ADQI 23 (2020) consensus. Focusing on three major clinical scenarios—cardiac surgery, sepsis, and nephrotoxic drugs—it reviews early biomarker evidence and explores their potential applications in risk stratification. At the mechanistic level, this paper outlines key pathological pathways in pediatric AKI progression: oxygenation-perfusion imbalance after cardiac surgery, endothelium-immune dysregulation driven by sepsis, and tubular-mitochondrial injury associated with nephrotoxic exposure. In CS-AKI, uNGAL shows the earliest elevation within hours after cardiopulmonary bypass, followed by sequential changes in IL-18, L-FABP, and KIM-1. [TIMP-2] × [IGFBP7] and exosomal miRNA aid in identifying high-risk or severe AKI. In SA-AKI, suPAR and glycocalyx/endothelial injury markers (e.g., syndecan-1, Angpt-2/sTM/Tie-2), combined with urinary DKK3 and complement Ba, can be used for early risk stratification and predicting poor outcomes. In NT-AKI, uNGAL has high negative predictive value for excluding severe AKI, while uKIM-1, uCysC, uOPN, and multi-biomarker combinations can indicate subclinical tubular injury earlier after drug exposure. Overall, single biomarkers struggle to cover AKI heterogeneity. Future efforts should integrate functional dynamic assessments (e.g., FST, RRI), scenario-based multi-biomarker combinations, and AI dynamic models to propose evidence-based, scenario-stratified identification pathways. These will serve as structured references for prospective studies and clinical workflow optimization.

Inflammatory response is considered a critical component in developing cerebral ischemia/reperfusion injury (CI/RI). Dynamin-related protein 1 (Drp1) performs an essential role in initiating and advancing CI/RI-induced inflammatory reactions. The objective of the present study was to investigate whether Fuzheng Jiedu Tongluo Granule (FZJDTL) attenuated CI/RI by modulating the Drp1-mediated TXNIP/NLRP3 pathway in vivo and in vitro. Molecular docking and molecular dynamics simulations validated the interactions between the core target and the main components of FZJDTL. Oxygen–glucose deprivation/reoxygenation (OGD/R) in PC12 cells and middle cerebral artery occlusion/reperfusion (MCAO/R) in rats were established. Then, the neuroprotective effects of FZJDTL in MCAO/R rats were assessed using brain infarct volume, HE staining, and neurological deficit scores. The levels of inflammatory factors were detected by ELISA. We further examined whether the neuroprotective effect of FZJDTL on MCAO/R in rats and OGD/R in PC12 cells was connected to the suppression of the Drp1-mediated TXNIP/NLRP3 pathway through methods of Western blot and RT-qPCR. Molecular docking and molecular dynamics simulations revealed that the principal components of FZJDTL exhibited favorable binding affinity with Drp1. The results demonstrated that FZJDTL mitigated pathological brain damage, ameliorated neurological impairments, and reduced the volume of cerebral infarction. FZJDTL inhibited the production of ROS and inflammatory factors (IL-1β, IL-18). In vivo and in vitro studies revealed that the neuroprotective effect of FZJDTL was associated with Drp1-mediated modulation of the inflammatory response, as evidenced by the suppression of mRNA and protein expression of p-Drp1, TXNIP, NLRP3, GSDMD, GSDMD-N, Caspase-1, Cleaved caspase-1, and ASC. Besides, FZJDTL significantly upregulated the mRNA and protein expression of OPA1 and TRX, as verified by RT-qPCR and Western blot analysis. Taken together, treatment with FZJDTL attenuated CI/RI by reducing the inflammatory response via the Drp1-mediated TXNIP/NLRP3 pathway.

Hepatoprotective natural compounds are pivotal constituents for the formulation of functional foods and the prophylaxis of hepatic disorders. To enhance the efficiency and reliability of hepatoprotective compound discovery, we propose a new predictive framework named HP-MoleQ. It comprises a pretrained Transformer and an uncertainty quantification module. HP-MoleQ outperforms existing models and enables high-confidence screening of the FoodB database. Compounds are ranked according to 95

Ischemic stroke is a leading cerebrovascular disorder frequently complicated by cerebral ischemia-reperfusion injury (CIRI), which aggravates neurological damage and worsens clinical outcomes. Yangyin Formula (YYF), a traditional Chinese medicine composed of Rehmannia glutinosa, Dendrobium officinale, and Pueraria lobata, has shown potential in mitigating CIRI. To elucidate its therapeutic mechanisms, we integrated network pharmacology, molecular docking, and molecular dynamics simulations, followed by in vivo validation in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). A total of 61 bioactive compounds and 768 targets were identified, enriched in 136 signaling pathways. Computational analyses revealed strong binding affinities between key YYF components and CIRI-related targets. In vivo, YYF administration significantly improved neurological function, reduced infarct volume, and alleviated histopathological damage. Furthermore, YYF suppressed IL-17A, TNF-α, IL-1β, Caspase-3, p38 MAPK, and NF-κB p65 expression in brain and serum, with effects comparable to IL-17A inhibition. These findings suggest that YYF exerts neuroprotective effects against CIRI by modulating the IL-17A/p38 MAPK/NF-κB p65 signaling pathway, highlighting its potential as a therapeutic strategy for ischemic stroke.