BACKGROUND:In recent years,epidemiological studies have shown that sleep patterns are risk factors for osteoarthritis,but the causal relationship between sleep characteristics and osteoarthritis remains unknown. OBJECTIVE:To investigate the causal relationship between seven sleep phenotypes and osteoarthritis,thereby providing a theoretical foundation for clinical prevention and intervention of osteoarthritis. METHODS:Seven sleep-related features,namely sleep duration,wake-up time,daytime napping,morning/evening preference,snoring,insomnia,and hypersomnia,were selected from published genome-wide association studies.Instrumental variables for these sleep-related features were extracted.Instrumental variables for knee osteoarthritis and hip osteoarthritis were obtained from publicly available genome-wide association studies.Causal relationships between sleep characteristics and outcome risks were evaluated using two-sample and multivariable Mendelian randomization analyses.The inverse variance weighted method was employed as the primary Mendelian randomization approach.Various methods,including weighted median,weighted mode,Mendelian randomization-Egger regression,Mendelian randomization pleiotropy-residual sum and outlier,were utilized to detect and correct for the presence of pleiotropy. RESULTS AND CONCLUSION:The results of the inverse variance-weighted method in the two-sample Mendelian randomization study revealed a detrimental causal association between the duration of sleep and the incidence risk of knee osteoarthritis[odds ratio(OR)=0.621,95%confidence interval(CI):0.470-0.822,P=0.001].Concurrently,insomnia displayed a positive causal connection with hip osteoarthritis risk(OR=2.016,95%CI:1.249-3.254,P=0.005).Sensitivity analysis affirmed the robustness of these causal relationships,and Mendelian randomization-Egger intercept analysis found no evidence of potential horizontal pleiotropy(knee osteoarthritis:P=0.468,hip osteoarthritis:P=0.551).Moreover,the results from the multivariable Mendelian randomization analysis showed that the causal association between insomnia and hip osteoarthritis lacked statistical significance(P=0.715).In contrast,sleep duration exhibited a direct negative causal relationship with the incidence risk of knee osteoarthritis(OR=0.526,95%CI:0.336-0.824,P=0.005).Reverse Mendelian randomization analysis indicated that knee osteoarthritis did not influence sleep duration(P=0.757).These findings indicate a negative correlation between sleep duration and incidence risk of knee osteoarthritis,suggesting that correcting insufficient sleep might mitigate the incidence risk of knee osteoarthritis.

Knee osteoarthritis （KOA） is a common degenerative joint disease characterized primarily by the degeneration and damage of knee joint cartilage， accompanied by osteophyte formation and inflammation. In recent years， the prevalence of KOA has been increasing globally， significantly impacting the quality of life patients. However， the pathogenesis of KOA remains not fully understood， and current treatment methods are limited. Therefore， finding new therapeutic strategies is a research hotspot. Previous studies have found that the onset of KOA is related to abnormal mitochondrial regulation. Mitochondria， functioning as secondary messengers， play crucial roles in cellular respiration， reactive oxygen species （ROS） generation， and adenosine triphosphate （ATP） production through oxidative phosphorylation. Mitochondrial quality control is a pivotal mechanism for maintaining the morphology， quantity， and quality of mitochondria. The connection between mitochondrial quality control and the pathogenesis of KOA involves several factors， such as mitochondrial oxidative stress， mitophagy， imbalances in mitochondrial biogenesis， abnormal mitochondrial dynamics （fission and fusion）， and dysregulation of calcium ions. Metabolic abnormalities in the body lead to mitochondrial structural damage， which in turn contributes to the onset and progression of KOA. Traditional Chinese medicine （TCM） has made some progress in intervening in mitochondrial quality control， employing multi-faceted， multi-pathway， and multi-target strategies to treat KOA. Several studies have shown that mitochondrial quality control may be one of the therapeutic targets of TCM in treating KOA. However， there is currently a lack of comprehensive reviews summarizing the TCM interventions in mitochondrial quality control for treating KOA. This paper systematically reviewed the research progress in TCM treatment of KOA based on five aspects of mitochondrial quality control， aiming to provide a theoretical basis for the clinical prevention and treatment of KOA.

OBJECTIVE To conduct a reevaluation of the systematic review （SR）/meta-analysis on the use of Xianling gubao capsules （XLGBC） for knee osteoarthritis （KOA）， and provide evidence-based support for the clinical use of the drugs. METHODS Computerized searches including CNKI， Wanfang Data， VIP， China Biomedical Literature Database， the Cochrane Library， PubMed， Embase and Web of Science were conducted to collect systematic reviews （SR） or meta-analyses of XLGBC for the treatment of KOA from the inception to May 31st， 2024. The report quality， methodological quality， risk of bias and evidence quality were assessed using the PRISMA 2020 statement， AMSTAR 2 scale， ROBIS tool and GRADE tool， respectively. A comprehensive quality analysis of the quantitative results from the SR/meta-analysis was also performed. RESULTS A total of five SR/meta-analyses were included. The evaluation results based on the PRISMA 2020 statement showed that one study report was relatively complete （21 points）， while four studies had deficiencies （18-20 points）. The assessment using the AMSTAR 2 scale indicated that the methodological quality of all five studies was rated as very low. According to the ROBIS tool evaluation， the risk of comprehensive bias in all five studies was classified as high. GRADE tool evaluation revealed that among 49 outcome indicators， 5 （10.2%） were rated as moderate-quality evidence （10.2%）， 12 as low-quality evidence （24.5%）， and 32 as very low-quality evidence （65.3%）. The results of comprehensive quality analysis showed that the clinical efficacy， visual analogue scale score， pain relief time， comprehensive indexes of knee joint function， the levels of inflammatory factors and the incidence of adverse events in patients with XLGBC combined with conventional treatment were significantly better than conventional treatment alone （P＜0.05）. CONCLUSIONS Compared with conventional treatment， XLGBC in combination with conventional treatment for KOA may have some efficacy and safety advantages. However， due to the low quality of evidence for the outcome indicators included in the studies， the conclusions should be interpreted with caution.

OBJECTIVE To conduct a reevaluation of the systematic review （SR）/meta-analysis on the use of Xianling gubao capsules （XLGBC） for knee osteoarthritis （KOA）， and provide evidence-based support for the clinical use of the drugs. METHODS Computerized searches including CNKI， Wanfang Data， VIP， China Biomedical Literature Database， the Cochrane Library， PubMed， Embase and Web of Science were conducted to collect systematic reviews （SR） or meta-analyses of XLGBC for the treatment of KOA from the inception to May 31st， 2024. The report quality， methodological quality， risk of bias and evidence quality were assessed using the PRISMA 2020 statement， AMSTAR 2 scale， ROBIS tool and GRADE tool， respectively. A comprehensive quality analysis of the quantitative results from the SR/meta-analysis was also performed. RESULTS A total of five SR/meta-analyses were included. The evaluation results based on the PRISMA 2020 statement showed that one study report was relatively complete （21 points）， while four studies had deficiencies （18-20 points）. The assessment using the AMSTAR 2 scale indicated that the methodological quality of all five studies was rated as very low. According to the ROBIS tool evaluation， the risk of comprehensive bias in all five studies was classified as high. GRADE tool evaluation revealed that among 49 outcome indicators， 5 （10.2%） were rated as moderate-quality evidence （10.2%）， 12 as low-quality evidence （24.5%）， and 32 as very low-quality evidence （65.3%）. The results of comprehensive quality analysis showed that the clinical efficacy， visual analogue scale score， pain relief time， comprehensive indexes of knee joint function， the levels of inflammatory factors and the incidence of adverse events in patients with XLGBC combined with conventional treatment were significantly better than conventional treatment alone （P＜0.05）. CONCLUSIONS Compared with conventional treatment， XLGBC in combination with conventional treatment for KOA may have some efficacy and safety advantages. However， due to the low quality of evidence for the outcome indicators included in the studies， the conclusions should be interpreted with caution.