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.

Objective To investigate the causal relationship between gut microbiota and pigmented villonodular synovitis using Mendelian randomization analysis.Methods We conducted a two-sample Mendelian randomization analysis to investigate the causal relationship between 211 gut microbiome taxa and pigmented villonodular synovitis based on GWAS summary data,with inverse variance weighted(IVW)analysis as the primary result and the other methods as supplementary analyses.The reliability of the results was tested using Cochran's Q test,MR-Egger regression,MR-PRESSO method and conditional Mendelian randomization analysis(cML-MA).Results The increased abundance of Barnesiella(OR=3.12,95%CI:1.15-8.41,P=0.025)and Rumatococcaceae UCG010(OR=4.03,95%CI:1.19-13.68,P=0.025)may increase the risk of pigmented villous nodular synovitis,and elevated abundance of Lachnospiraceae(OR=0.33,95%CI:0.12-0.91,P=0.032),Alistipes(OR=0.16,95%CI:0.05-0.53,P=0.003),Blautia(OR=0.20,95%CI:0.06-0.61,P=0.005),and Lachnospiraceae FCS020 group(OR=0.38,95%CI:0.15-0.94,P=0.036)and Ruminococcaceae UCG014(OR=0.36,95%CI:0.14-0.94,P=0.037)were all associated with a reduced risk of pigmented villonodular synovitis,which were supported by the results of sensitivity analyses.Reverse Mendelian randomization analysis did not reveal any inverse causal association.Conclusion Increased abundance of specific intestinal microorganisms is associated with increased or decreased risks of developing hyperpigmented villonodular synovitis,and gut microbiota plays an important role in the pathogenesis of this disease.

Objective To investigate the causal relationship between gut microbiota and pigmented villonodular synovitis using Mendelian randomization analysis.Methods We conducted a two-sample Mendelian randomization analysis to investigate the causal relationship between 211 gut microbiome taxa and pigmented villonodular synovitis based on GWAS summary data,with inverse variance weighted(IVW)analysis as the primary result and the other methods as supplementary analyses.The reliability of the results was tested using Cochran's Q test,MR-Egger regression,MR-PRESSO method and conditional Mendelian randomization analysis(cML-MA).Results The increased abundance of Barnesiella(OR=3.12,95%CI:1.15-8.41,P=0.025)and Rumatococcaceae UCG010(OR=4.03,95%CI:1.19-13.68,P=0.025)may increase the risk of pigmented villous nodular synovitis,and elevated abundance of Lachnospiraceae(OR=0.33,95%CI:0.12-0.91,P=0.032),Alistipes(OR=0.16,95%CI:0.05-0.53,P=0.003),Blautia(OR=0.20,95%CI:0.06-0.61,P=0.005),and Lachnospiraceae FCS020 group(OR=0.38,95%CI:0.15-0.94,P=0.036)and Ruminococcaceae UCG014(OR=0.36,95%CI:0.14-0.94,P=0.037)were all associated with a reduced risk of pigmented villonodular synovitis,which were supported by the results of sensitivity analyses.Reverse Mendelian randomization analysis did not reveal any inverse causal association.Conclusion Increased abundance of specific intestinal microorganisms is associated with increased or decreased risks of developing hyperpigmented villonodular synovitis,and gut microbiota plays an important role in the pathogenesis of this disease.

Objective To compare the clinical efficacy of ankle arthroscopy combined with closed reduction guide and conventional surgical incision in the treatment of trimalleolar fracture.Methods A total of 60 patients with ankle fracture were divided into two groups according to different surgical plans:the ankle arthroscopy combined with closed reduction guide surgery group(arthroscopy group)and the conventional incision surgery group(incision group),with 30 cases in each group.The operative time,intraoperative blood loss and complications of the two groups were observed and compared.Pain and functional recovery of patients were evaluated by the American Orthopaedic Foot&Ankle Society(AOFAS)ankle and hind foot scores and Foot and Ankle Disability Index(FADI)scores.Results All 60 patients were followed up.Compared with the arthroscopy group,patients in the incision group had a longer surgical time,a shorter incision length in the medial malleolus,a reduced number of cases of skin numbness and reduced bleeding(P＜0.05).The AOFAS score and the FADI score at 12 months after surgery were higher in the arthroscopic group than those of the incision group(P＜0.05).After 12 months of surgery,the AOFAS score in patients without cartilage injury of the arthroscopic group were higher than those of patients with cartilage injury(P＜0.05),while there were no significant differences in pain and force line scores between patients with cartilage injury and patients without cartilage injury(P＞0.05).Conclusion The application of ankle arthroscopy combined with closed reduction guide in the treatment of trimalleolar fracture can achieve better postoperative results,but it has no obvious advantages in operation time and incision infection compared with the incision surgery.

Objective:To investigate the application value of nectin-4 targeting radiotracer 68Ga-N188 in the diagnosis of pancreatic cancer. Methods:The prospective study was conducted. The clinicopathologic data of 16 patients diagnosed as pancreatic cancer on enhanced computed tomography (CT) who were admitted to the Peking University First Hospital from August to December 2022 were collected. There were 9 males and 7 females, aged (62±8)years. All patients underwent 18F-flurodeoxyglucose ( 18F-FDG) and 68Ga-N188 positron emission tomography (PET)/CT examination. Observation indicators: (1) distribution of 68Ga-N188 in different tissues and tumor primary lesion of patients; (2) expression of Nectin-4 and uptake of 68Ga-N188 in pancreatic cancer; (3) comparison of examination results between 68Ga-N188 and 18F-FDG PET/CT. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Count data were described as absolute numbers or percentages. Results:(1) Distribution of 68Ga-N188 in different tissues and tumor primary lesion of patients. Results of PET/CT examination showed that in 1 hour after injection, the maximum standard uptake value (SUVmax) and mean standard uptake value (SUVmean) of 68Ga-N188 in fat, muscle, skin, and brain tissues of 16 patients were 0.40±0.16 and 0.25±0.09, 0.68±0.20 and 0.44±0.12, 0.39±0.14 and 0.28±0.11, 0.09±0.04 and 0.05±0.02, respectively. In the tissues of the esophagus, liver, spleen, and pancreas, the above indicators were 1.53±0.48 and 1.16±0.31, 1.49±0.45 and 0.91±0.30, 1.40±0.30 and 1.02±0.24, 1.24±0.31 and 0.96±0.25, respectively. In tumor primary lesion, the above indicators were 3.28±1.02 and 2.14±0.62, respectively, showing significant differences in SUVmax and SUVmean compared with pancreatic tissue ( t=8.03, 6.75, P<0.05). The tumor background ratio in tumor primary lesion based on SUVmax was 1.82±0.58. (2) Expression of Nectin-4 and uptake of 68Ga-N188 in pancreatic cancer. Results of immunohistochemical staining in 16 patients showed that there were 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression. Results of PET/CT examination showed that the SUVmax of 68Ga-N188 in tumor primary lesion of the 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression were 3.77±1.10 and 2.64±0.68, showing a significant difference between them ( t=2.64, P<0.05). The SUVmax of 18F-FDG in tumor primary lesion of the 7 patients with high Nectin-4 expression and 9 patients with low Nectin-4 expression were 6.73±3.24 and 6.43±3.45, showing no significant difference between them ( t=0.17, P>0.05). (3) Comparison of examination results between 68Ga-N188 and 18F-FDG PET/CT. Of the 16 patients, cases with positive results of tumor primary lesion on 68Ga-N188 and 18F-FDG PET/CT were 14 and 11, respectively, for the 14 pancreatic cancer patients diagnosed by postoperative histopathology. Among them, cases with positive results of tumor primary lesion on 68Ga-N188 and 18F-FDG PET/CT were 3 and 1 for the 3 pancreatic cancer patients receiving evaluation for chemotherapy. The SUVmax of 18F-FDG in tumor primary lesion of the 3 patients with chemotherapy and the 11 patients without chemotherapy were 2.80±0.69 and 6.97±2.11, showing a significant difference between them ( t=3.29, P<0.05). The SUVmax of 68Ga-N188 in tumor primary lesion of the 3 patients with chemotherapy and the 11 patients without chemotherapy were 3.38±1.12 and 2.93±0.50, showing no significant difference between them ( t=0.66, P>0.05). Cases with positive results of lymph node metastases in 68Ga-N188 and 18F-FDG PET/CT were 6 and 4, respectively, for the 6 pancreatic cancer patients diagnosed with lymph node metastases by postoperative histopathology, and the SUVmax of 68Ga-N188 and 18F-FDG in lymph node metastases were 2.25±1.12 and 4.02±1.27. Conclusion:68Ga-N188 PET/CT can be used for imaging diagnosis of tumor primary lesion and lymph node metastases of pancreatic cancer.

BACKGROUND:Based on different algorithms of machine learning,how to carry out clinical research on lumbar disc herniation with the help of various algorithmic models has become a trend and hot spot in the development of intelligent medicine at present. OBJECTIVE:To review the characteristics of different algorithmic models of machine learning in the diagnosis and treatment of lumbar disc herniation,and summarize the respective advantages and application strategies of algorithmic models for the same purpose. METHODS:The computer searched PubMed,Web of Science,EMBASE,CNKI,WanFang,VIP and China Biomedical(CBM)databases to extract the relevant articles on machine learning in the diagnosis and treatment of lumbar disc herniation.Finally,96 articles were included for analysis. RESULTS AND CONCLUSION:(1)Different algorithm models of machine learning provide intelligent and accurate application strategies for clinical diagnosis and treatment of lumbar disc herniation.(2)Traditional statistical methods and decision trees in supervised learning are simple and efficient in exploring risk factors and establishing diagnostic and prognostic models.Support vector machine is suitable for small data sets with high-dimensional features.As a nonlinear classifier,it can be applied to the recognition,segmentation and classification of normal or degenerative intervertebral discs,and to establish diagnostic and prognostic models.Ensemble learning can make up for the shortcomings of a single model.It has the ability to deal with high-dimensional data and improve the precision and accuracy of clinical prediction models.Artificial neural network improves the learning ability of the model,and can be applied to intervertebral disc recognition,classification and making clinical prediction models.On the basis of the above uses,deep learning can also optimize images and assist surgical operations.It is the most widely used model with the best performance in the diagnosis and treatment of lumbar disc herniation.The clustering algorithm in unsupervised learning is mainly used for disc segmentation and classification of different herniated segments.However,the clinical application of semi-supervised learning is relatively less.(3)At present,machine learning has certain clinical advantages in the identification and segmentation of lumbar intervertebral discs,classification and grading of the degenerative intervertebral discs,automatic clinical diagnosis and classification,construction of the clinical predictive model and auxiliary operation.(4)In recent years,the research strategy of machine learning has changed to the neural network and deep learning,and the deep learning algorithm with stronger learning ability will be the key to realizing intelligent medical treatment in the future.

BACKGROUND:Anterior cruciate ligament rupture is one of the injuries that seriously affect life and sports performance,and the anterior cruciate ligament as a stabilizing structure is irreplaceable in maintaining sports performance.In view of its severe injury manifestations,the current treatment for anterior cruciate ligament rupture is a surgery for anterior cruciate ligament reconstruction.Since an anterior cruciate ligament injury can cause loss of mechanoreceptors,which in turn causes a reduction in proprioception,it is a great problem for patients to recover their motor performance. OBJECTIVE:To summarize the effects of proprioceptive training on clinical outcomes after anterior cruciate ligament reconstruction and to explore the underlying mechanisms,thereby providing more references for clinical prevention and treatment. METHODS:A computerized search of PubMed,CNKI,WanFang Data,and VIP databases was conducted for literature(from January 2013 to March 2023)related to proprioceptive training after anterior cruciate ligament reconstruction that improves joint stability and motor balance ability.A total of 108 articles were finally included for review. RESULTS AND CONCLUSION:Proprioceptive training can effectively improve the proprioceptive functions of patients,such as positional sense and kinesthetic sense after anterior cruciate ligament reconstruction,and improve joint stability,postural control and motor ability.The proprioceptive training improves the proprioceptive function through three mechanisms:stimulation of periprosthetic receptors around the knee joint,activation of spinal reflex stimulation,reinforcement of motor control in the brain,and enhancement of cognitive processing.The proprioceptive training may improve proprioceptive functions by activating the potential mechanisms of growth associated protein-43 activity,Piezo2 mechanotransducer,and NT-3/TrkC signaling pathway.Hydrotherapy is the mainstay in the early stages,while neuromuscular training,individual strength training and visual feedback training are prioritized in the middle and late stages.There exists an as-yet-unsegmented reconstructive surgery graft,sex,and a lack of devices or proprioceptive training methods based on the idea of combining multiple sensory stimuli.

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.

Objectives:To investigate the effect of inhibition of long non-coding RNA(lnc RNA)in human metastasis associated lung adenocarcinoma transcript 1(MALAT1)on glycolipitoxicity-induced human umbilical vein endothelial cell dysfunction. Methods:Human umbilical vein endothelial cells were treated with glucose and palmitic acid in vitro to establish the glycolipitoxic endothelial cell models.Following groups were examined:control group,high-glucose and high-fat group,high-glucose and high-fat + non-targeting RAN control group,high-glucose and high-lipid+MALAT1 siRNA group,and high-glucose and high-lipid+MAPK1 siRNA group.RT-qPCR was used to detect the mRNA expression of MALAT1 and MAPK1.Western blot was used to detect the expression levels of autophagy,mitochondrial fusion division,apoptosis,and pathway-related proteins.Immunofluorescence confocal localization was used to detect the fluorescence colocalization of autophagy and lysosome-related proteins.The number of autophagolysosomes in endothelial cells was observed by transmission electron microscopy.Mitochondrial probe staining was used to detect mitochondrial morphology,immunofluorescence was used to detect intracellular reactive oxygen species(ROS)production,flow cytometry was used to detect the apoptosis of cells in each group,cell proliferation and scratch assays were used to detect the proliferation and migration ability of cells in different groups at different time points.The angiogenesis was quantified by counting the number of new blood vessels in each group. Results:Compared with the control group,the expression of lncRNA MALAT1 mRNA and the expression of phosphorylated mito-activated protein kinase 1(p-MAPK1)were upregulated(both P＜0.05)and the expression of phosphorylated mammalian target protein(p-mTOR)was downregulated in the high-glucose and high-fat group and the high-sugar and high-fat control group(all P＜0.01).Compared with the high-glucose and high-fat non-targeting RNA control group,the expressions of microtubule-associated protein 1A/1B-light chain 3(LC3)and p62 were downregulated(P＜0.01,P＜0.05),LC3 and lysosome-associated membrane protein 2(LAMP2)protein co-localized positive fluorescence particles were increased(both P＜0.01),number of lysosomes were decreased,the expression of ROS was decreased(P＜0.01),the expression level of mitochondrial fusion protein optic nerve atrophin 1(OPA1)was increased(P＜0.05),the expressions of cleaved caspase-3 and BCL-2-related X protein(BAX)were decreased and BCL-2 was increased(all P＜0.05),cell proliferation,migration,and tube-forming ability were increased(all P＜0.01),and the expression of p-MAPK1 was decreased(P＜0.05)and p-mTOR expression was increased(both P＜0.05)in the high-glucose and high-lipid+si-MALAT1 group.Compared with the high-glucose and high-fat non-targeting RNA control group,the expression of p-MAPK1 in endothelial cells was decreased and the expression of p-mTOR was increased in the high-glucose and high-lipid+si-MAPK1 group(both P＜0.01). Conclusions:Inhibition of lncRNA MALAT1 expression can reduce the level of mitophagy in glycolipidotoxic environments,reduce apoptosis of endothelial cells and improve endothelial cell function,which may be related to the regulation of MAPK1/mTOR signaling pathway.