Objective:To investigate the mechanism of Juanbi Capsules in the intervention of knee osteoarthritis by inhibiting lipid peroxidation and chondrocyte ferroptosis through activating nuclear factor E2 related factor (Nrf2)/glutathione peroxidase 4 (GPx4) signaling pathway.Methods:Totally 45 rats were randomly divided into blank group, model group and Juanbi Capsules low-, medium- and high-dosage groups, with 9 rats in each group. Except the blank group, the other groups were injected with sodium monoiodoacetate (MIA) to establish knee osteoarthritis model. From the third week of modeling, rats in Juanbi Capsules low-, medium- and high-dosage groups were gavaged with 108.05, 216.09, and 432.18 mg/kg of Juanbi Capsules suspension, and rats in the blank group and model group were gavaged with equal volume of normal saline, once a day, for 28 consecutive days. HE and safranine fast green staining were used to observe the pathological changes of cartilage tissue, and Mankin's score was performed; the levels of MDA, Fe 2+, glutathione (GSH) in articular cartilage were detected by biochemical kit; Western blot was used to detect the protein expressions of SLC7A11, GPx4, acsll4 and Nrf2 in rat articular cartilage. Results:Compared with the model group, the Mankin's score was significantly lower in the Juanbi Capsules middle- and high-dosage groups ( P<0.01); the MDA level decreased in Juanbi Capsules low-, medium- and high-dosage groups ( P<0.01), GSH level increased ( P<0.01), and and Fe 2+ level decreased Juanbi Capsules middle- and high-dosage groups ( P<0.01, P<0.05); the protein expressions of Nrf2, SLC7A11 and GPx4 in cartilage tissue of Juanbi Capsules middle- and high-dosage groups increased ( P<0.01 or P<0.05), the expression of ACSl4 protein decreased ( P<0.01 or P<0.05), and SLC7A11 protein expression increased in Juanbi Capsules low-dosage group ( P<0.05). Conclusion:Juanbi Capsule may inhibit the ferroptosis of rat articular cartilage by activating the Nrf2/GPX4 signaling pathway.

Osteoarthritis(OA)is a degenerative joint disease primarily characterized by articular cartilage degeneration.Autophagy is a crucial intracellular homeostatic system that plays a vital role in maintaining normal cartilage function.By regulating cell apoptosis and repairing damaged chondro-cytes,autophagy protects cartilage,and dysfunction in chondrocyte autophagy is an important patho-genic mechanism underlying cartilage degeneration in OA.MicroRNAs(miRNA)can regulate gene expression and play a key role in chondrocyte development and functional maintenance.MiRNA in-volved in the regulation of autophagy are aberrantly expressed in OA,suggesting that miRNAs may serve as potential targets and biomarkers for early prediction,diagnosis,and effective treatment of OA.This review discussed the role of autophagy in OA and the regulatory role of miRNA in OA de-velopment,with a focus on the role of miRNA-mediated regulation of chondrocyte autophagy in OA pathogenesis and its potential therapeutic value.

OBJECTIVE To confirm the therapeutic effect of Jintiange capsules on osteoarthritis(OA) and the potential mechanism of synovial mesenchymal stem cell exosomes(SMSC-Exos) and articular chondrocytes(ACs) in the treatment of OA based on high-throughput sequencing technology. METHODS Type Ⅱ collagenase-induced OA rats were used for efficacy verification through general behavioral observation, bipedal balance difference experiment, mechanical foot reflex threshold, Micro-CT observation, and Safranin O-Fast Green staining. SMSCs and ACs were cultured in suitable concentration of drug-containing serum, and mRNA sequencing was performed on ACs in the control, model, and Jintiange capsules groups, as well as miRNA sequencing on SMSC-Exos. Differential expressed mRNAs and miRNAs were screened and target genes were predicted. The common differential expressed genes between SMSC and ACs were obtained by intersecting the differential expressed genes, and a miRNA-mRNA regulatory network was constructed using Cytoscape software. The expression trend analysis of common differential expressed genes was conducted, as well as the correlation analysis between differential expressed gene mRNA and miRNA, Micro-CT efficacy indicators, and differential expressed gene mRNA. RESULTS Under the pathological state of OA, the expression of miRNA-23a-3p, miRNA-342-3p, miRNA-146b-5p, miRNA-501-3p, and miRNA-214-3p were down-regulated, while miRNA-222-3p, miRNA-30e-3p, miRNA-676-3p, and miRNA-192-5p were up-regulated (P<0.05). The expressions of these miRNAs were significantly reversed after intervention with drug-containing serum of Jintiange capsules. There was a certain correlation between Micro-CT efficacy indicators, mRNA and miRNA. CONCLUSION Jintiange capsule has obvious efficacy in the treatment of OA, and its mechanism may be related to the promotion of SMSC-Exos targeting ACs to transport miRNA and then regulate Serpinb10, Ntn1, Il1b, Tgm2, Megf10, Il11, Cd40, Slc15a3, Pou2f2 and other genes.

Osteoarthritis (OA) is a common chronic degenerative disease of joints, which is one of the main causes of chronic pain and disability. Several studies have shown that OA is causally associated with many factors, such as cytokines, metabolic diseases, nutrients, gut microbiota, and life behaviors. The risk factors included obesity, hyperlipidemia and bone mineral density, and the protective factors included the use of potassium-sparing diuretics and aldosterone antagonists, folic acid and arginine. These factors influence the progression of OA mainly by participating in the body's inflammatory response and material metabolic processes or by altering the biomechanics of weight-bearing joints. In addition, the chronic pain symptoms of OA, the expression of inflammatory factors, and the use of non-steroidal anti-inflammatory drugs may increase the risk of other diseases, such as type 2 diabetes, severe depression, and Parkinson's disease. Mendelian randomization is a new method to explore the causal association between diseases and risk factors. This method uses the random allocation of genetic variants to simulate randomized controlled trials and uses the instrumental variables related to risk factors and diseases to test the causal association between them. This review included the Mendelian randomization-related studies of OA and analyzed the causal association between OA and metabolic diseases, cardiovascular diseases, musculoskeletal diseases, central nervous system diseases, psychiatric diseases, cytokines, metabolomics, nutrients, gut microbiota, life behavior, telomere length and mitochondrial heterogeneity, which is of great significance for the prevention and treatment of OA.

【Objective】 We combined the concept of traditional medicine with magnetic induction technology, originally brought up the research concept of magnetic hyperthermia to cure KOA, explored the mechanism and constructed a new treatment of KOA with modern medical features. 【Methods】 Through establishing a primary KOA model in rats and constructing ferrimagnetic vortex domain iron oxide nanorings (FVIOs) as a platform for highly efficient magnetic hyperthermia agent, the lesions of KOA were heated accurately under the low-intensity magnetic field. We confirmed the curative effect through the results of pain perception, histopathology, knee joint morphology and microscopic bone structure and the content of serum inflammatory factor, to study the therapeutic mechanism of magnetic hyperthermia for KOA. 【Results】 Compared with the model group, the recovery of mechanical pain threshold after magnetic hyperthermia improved by approximately 48.9%; the degree of hyperemia and edema of joint capsule and synovial tissue and the wear degree of joint cartilage surface, were significantly reduced; the Mankin and OARSI scores decreased by about 33% and 20%, respectively; the MicroCT results indicated that the degree of hardening of the subchondral bone also improved; the expression of inflammatory factors in the serum was reduced. 【Conclusion】 In this study, we utilized the FVIOs as a high-efficiency magnetic hyperthermia platform for the treatment of KOA. The efficacy of magnetic hyperthermia on KOA is clarified, and the mechanism is related to the inhibition of inflammatory factors.

【Objective】 Through bioinformatics methods to analyze the differences in the gene expression profiles of peripheral blood mononuclear cells （PBMCs） between middle-aged and elderly women and normal people， so as to explore the diagnosis and treatment targets of OA. 【Methods】 We downloaded the GSE48556 data set from GEO databases. We utilized the R language to screen out the differentially expressed genes （DEGs） between OA and NC. By gene set enrichment analysis （GSEA）， we obtained the target gene subset. The GO and KEGG pathways of the target gene subset were analyzed by DAVID. We applied STRING and Cytoscape software to construct PPI network. The module analysis was performed by the Mcode and centiscape plug-in， and the key genes were screened out by Cytohubba. 【Results】 By GSEA analysis and P.adjust <0.05 & |log2FC| >0.2， a total of 292 target genes were screened， consisting of 81 upregulated genes and 211 downregulated genes. The GO enrichment analysis of all target genes mainly focused on the biological functions， such as “regulation of NIK/NF-κB”， “monocytes”， “proliferation”， “regulation of apoptosis signaling pathway”， “TNF-mediated signaling pathway”， “regulation of Wnt signaling pathway”， “regulation of MAP kinase activity”， and “regulation of autophagy”. KEGG was mainly enriched in four pathways： cytotoxicity of natural killer cell mediation， TNF signaling pathway， MAPK signaling pathway， and apoptosis. We employed PPI network and related plug-ins to screen out eight core genes highly related to OA inflammation and apoptosis， namely， MAPK1， IL10， PTGS2， IL18， GSK3B， NFKBIA， TNFRSF1A， and EGR1. 【Conclusion】 Bioinformatics analysis revealed that the differences in PBMCs gene expressions between OA and NC were concentrated in the biological events of apoptosis and inflammation， making blood expression profile an effective breakthrough for monitoring OA target markers.

Objective To analyze the differentially expressed genes in peripheral blood of human immunodeficiency(HIV)/tubercle bacilli co-infected patients and explore the biological regulatory mechanism and network of key proteins,so as to provide new evidence for early diagnosis and clinical treatment of HIV/TB co-infected patients. Methods Microarray gene chip data of HIV/TB co-infected patients were downloaded from public databases GEO and imported into the analysis software GEO,STRING,PANTHER,and GenClip. The gene expression profiles,protein interaction networks,processes of molecular biology,and gene functions were analyzed. Results The expression profiles of 15 529 genes between the two groups of patients were similar,and gene expression profiles from 44 subjects were highly correlated. The 251 differentially expressed genes had good diagnostic capabilities in the differential diagnosis of HIV/TB infection. RPLP1 might be a key gene in the diagnosis of HIV/TB infection. The differentially expressed genes and positive regulators showed certain functions such as external stimuli,signal transduction pathways in cells,migration of neutrophils,and immunological and other relevant functionalities. Meanwhile,they may also be involved in free radical-related apoptosis,inflammation,and activation pathways. Conclusions A total of 251 differentially expressed genes are found to be able to distinguish simple HIV infection from HIV/TB infection. Protein-protein interaction network of top 40 differential expression genes includes RPLP1 gene,which is possibly associated with HIV/TB co-infection and may be involved in and the positive regulation of external stimuli,signal transduction pathways in cells,migration of neutrophils,and immunological functions. These findings may provide certain evidence for the diagnosis and treatment of HIV/TB infection.

Objective To analyze effect of intra-articular injections of sodium hyaluronate combined with diprospan in the treatment of hip osteoarthritis.Methods 90 patients with hip arthritis patients from January 2014 to July 2015 were randomly divided into observation group and control group.45 cases in each group.Control group was given Diprospan treatment, observation group was treated with articular injection of sodium hyaluronate combined with diprospan treatment.After 4 weeks of treatment,patients were followed up and recorded hip pain VAS score and WOMAC score, lipids and C-reactive protein levels, content changes in ESR and TNF-α.Results The patients after hip pain VAS score and WOMAC scores were better than control group(P<0.05).After observation group patients lipids and C-reactive protein were lower than control group(P<0.05).After treatment ESR and TNF-αof observation group were lower than control group’s(P<0.05).Conclusion Intra-articular injections of sodium hyaluronate combined with diprospan in treatment of hip arthritis has definite clinical effect.

The development of osteoarthritis (OA) is associated with the synovium around the joints, and the synovitis is closely related to the pain and swelling of OA. The synovitis is not only involved in the early OA, but also played an important role in the progression of OA throughout.

Objective To explore the mechanism of preventive effect of Chinese medicine with Replenishing kidney and invigorating Qi on osteoarthritis. Methods 72 male Long-eared white rabbits aged 4 months were randomly divided into six groups, A group (blank control group), B group (model group), C group (traditional Chinese medicine high-dose prevention group), D group (Chinese herbal medicine with medium-dose prevention group), E group (Chinese herbal medicine with low-dose prevention group), F group (glucose-amino acid hydrochloride capsules prevention group).All the animals apart from A group were established osteoarthritis model by immobilizing knee joint with plaster cast for 6 weeks. In the same time of immobilization, traditional Chinese medicine and glucose-amino acid hydrochloride capsules were given to C, D, E and F group for 4 weeks. Physiological saline was given to B group. After 6 weeks of modeling, synovial fluid was extracted and the changes of TNF-α in it were analyzed by ELISA. Results Articular cartilage degeneration of B group was most obviously compared with C, D, E and F group. There was a significant difference of TNF-α level in comparison of A and B group (P＜0.05), B and C, D, E and F group (P＜0.05), and among C, D and E group. Conclusion Chinese medicine with replenishing kidney and invigorating Qi can prevent osteoarthritis by reducing TNF-α level in synovial fluid, enhancing cartilage cell metabolism, and slowing down cartilage degradation.