Knee osteoarthritis (KOA) is a common degenerative disease of the joints, and the Huiyang Zhitong Plaster (HYZTP) formulation exhibits distinct therapeutic advantages in the clinical treatment of KOA. However, the underlying pharmacological mechanisms of HYZTP remain unclear. This study aimed to explore the mechanism underlying the therapeutic effect of HYZTP in the treatment of KOA. Methods: The active components and targets of HYZTP were identified from the TCMSP database, and the KOA-related genes were retrieved from the GeneCards database, Therapeutic Target Database (TDD) database, and Online Mendelian Inheritance in Man (OMIM) database. The potential targets related to both HYZTP and KOA were identified using the online Venny tool. Protein-protein interaction (PPI) network analysis was performed using the online STRING data analysis tool, and the network was optimized using Cytoscape. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were additionally performed using the Oebiotech cloud platform. The interactions between the core targets and active components of HYZTP were investigated by molecular docking, and animal experiments were conducted for investigating the mechanism of action of HYZTP in the treatment of KOA. Results: A total of 138 active components of HYZTP, which are associated with its therapeutic effect in the treatment of KOA, were identified by integrating the results of database search. Of the 129 targets, 39 key genes were found to be significantly enriched in the TNF, IL-17, HIF-1, and Toll-like receptor (TLR) signaling pathways. The results of molecular docking revealed that the key components of HYZTP, namely, beta-sitosterol and stigmasterol, exhibited a favorable binding potential for the targets in the TNF signaling pathway, including TNF-alpha, IL-1 beta, and AKT1. Further histopathological analysis revealed that HYZTP repaired cartilage damage in a rabbit model of KOA. The results of western blotting revealed that the expression levels of TNF-alpha, RIP1, CASP3, and BAX proteins were downregulated in the knee joint cartilage of the HYZTP group, compared to those of the model group. Conclusion: HYZTP likely hinders the progression of KOA by inhibiting the TNF signaling pathway and suppressing cellular apoptosis. The study provides novel insights into the underlying pharmacological mechanism of HYZTP in the treatment of KOA, providing a foundation for further research into the clinical applications of HYZTP.

Osteoarthritis (OA) causes pain and disability in the elderly and has placed a severe burden on healthcare worldwide. Excessive death and decreased density of chondrocytes are recognized as the major pathological characteristic of OA. Chondrocytes have been shown to have multiple forms of death, including apoptosis, pyroptosis, necroptosis, and ferroptosis. The excessive death of chondrocytes often forms a vicious circle with imbalanced chondrocytes extracellular matrix (ECM) metabolism. Therefore, inhibiting chondrocytes excessive death has become a key point that cannot be ignored in the development of OA treatment strategies. We summarized recent studies on the functions and mechanisms of different modes of chondrocyte death and potential therapeutic strategies for OA and offered our views. This may provide direction and theoretical support for formulating OA treatment strategies in the future.

Based on network pharmacology and molecular docking, this study seeks to investigate the mechanism of Taohong Siwu decoction (THSWD) in the treatment of avascular necrosis of the femoral head (AVNFH). The Traditional Chinese Medicine Systems Pharmacology database was used in this investigation to obtain the active ingredients and related targets for each pharmaceutical constituent in THSWD. To find disease-related targets, the terms "avascular necrosis of the femoral head," "necrosis of the femoral head," "steroid-induced necrosis of the femoral head," "osteonecrosis," and "avascular necrosis of the bone" were searched in the databases DisGeNET, GeneCards, Comparative Toxicogenomics Database, and MalaCards. Following the identification of the overlap targets of THSWD and AVNFH, enrichment analysis using gene ontology, Kyoto Encyclopedia of Genes and Genomes, Reactome, and WikiPathways was conducted. The "THSWD-drug-active compound-intersection gene-hub gene-AVNFH" network and protein-protein interaction network were built using Cytoscape 3.9.1 and string, and CytoHubba was used to screen hub genes. The binding activities of hub gene targets and key components were confirmed by molecular docking. 152 prospective therapeutic gene targets were found in the bioinformatics study of ONFH treated with THSWD, including 38 major gene targets and 10 hub gene targets. The enrichment analysis of 38 key therapeutic targets showed that the biological process of gene ontology analysis mainly involved cytokine-mediated signaling pathway, angiogenesis, cellular response to reactive oxygen species, death-inducing signaling complex. The Kyoto Encyclopedia of Genes and Genomes signaling pathway mainly involves TNF signaling pathway, IL-17 signaling pathway, and the Recactome pathway mainly involves Signaling by Interleukins, Apoptosis, and Intrinsic Pathway for Apoptosis. WikiPathways signaling pathway mainly involves TNF-related weak inducer of apoptosis signaling pathway, IL-18 signaling pathway. According to the findings of enrichment analysis, THSWD cured AVNFH by regulating angiogenesis, cellular hypoxia, inflammation, senescence, apoptosis, cytokines, and cellular proliferation through the aforementioned targets and signaling pathways. The primary component of THSWD exhibits a strong binding force with the key protein of AVNFH. This study sheds new light on the biological mechanism of THSWD in treating AVNFH by revealing the multi-component, multi-target, and multi-pathway features and molecular docking mechanism of THSWD.

目的 探讨内侧入路微创经皮钢板内固定(MIPPO)技术治疗胫骨远段闭合骨折的临床疗效.方法 采用内侧入路MIPPO技术治疗18 例胫骨远段闭合骨折患者.记录手术时间、术中出血量、骨折复位情况、骨折愈合时间、踝关节活动度及并发症发生情况,采用AOFAS踝关节评分评价疗效.结果 患者均获得随访,时间9～26 个月.手术时间85～120 min,术中出血量100～220 ml.骨折均对位对线可,踝关节面平整,关节间隙正常,患肢未见明显短缩、旋转和成角畸形.切口均愈合,无钢板外露及感染发生.骨折愈合时间4～10个月.末次随访时,AOFAS踝关节评分为 95～100 分;踝关节活动度:跖屈 40°～45°,背伸 40°～45°,内翻35°～40°,外翻30°～35°.结论 内侧入路MIPPO技术治疗胫骨远段闭合骨折复位效果较好,软组织损伤小,疗效满意.

Based on network pharmacology methods, we explored the mechanism of the classic Chinese medicine formula Coix seed decoction (CSD) in treating knee osteoarthritis (KOA). We searched each single drug in the CSD in the traditional Chinese medicine systematic pharmacology database in turn to obtain information on the active ingredients and target proteins of the CSD, and obtain the name of the genes corresponding to the target proteins through the UniProt database. We collected KOA-related genes from DisGeNET, GeneCards, comparative toxicogenomics database, and MalaCards database. The Venny online tool identified potential therapeutic targets by intersecting CSD and KOA target genes, while gene ontology and Kyoto encyclopedia of genes and genomes analysis was performed using the Oebiotech Cloud Platform. A protein-protein interaction network was established using the String database; a “CSD-active ingredient-target gene-KOA” network plot was constructed using Cytoscape 3.9.1 software and screened for key targets and hub targets. Finally, molecular docking was performed for hub genes with high Degree values. A total of 227 effective target genes for CSD and 8816 KOA-related target genes were obtained, as well as 191 cross-target genes for CSD and KOA. We screened 37 key gene targets and identified the top 10 hub target genes in descending order of Degree value using protein-protein interaction and Cytoscape 3.9.1 software (TNF, IL-6, MMP-9, IL-1β, AKT-1, VEGFα, STAT-3, PTGS-2, IL-4, TP53). Gene ontology analysis showed that the biological process of CSD treatment of KOA mainly involves cytokine-mediated signaling pathway, negative regulation of apoptotic process, cellular response to hypoxia, cellular response to cadmium ion, response to estradiol, and extrinsic apoptotic signaling pathway in absence of ligand. Kyoto encyclopedia of genes and genomes analysis revealed major signaling pathways including Cellular senescence, TNF signaling pathway, and PI3K-Akt signaling pathway. The molecular docking results show that the core components bind well to the core targets. In conclusion, CSD may exert therapeutic effects on KOA by inhibiting pathological processes such as inflammatory response, apoptosis, cellular senescence, and oxidative stress.