BACKGROUND:Some studies have confirmed the changes in the function of immune cell subsets such as monocytes,T cells,B cells,and natural killer cells(NK cells)in patients with osteoarthritis,but the specific regulatory mechanisms are unclear.OBJECTIVE:To explore the causal relationship between plasma metabolite-mediated immune cells and hip osteoarthritis.METHODS:The Genome-Wide Association Studies(GWAS)data of 731 immune cells were used as the exposure,the GWAS data of hip osteoarthritis were used as the outcome,and 1 400 plasma metabolites were selected as mediating factors.The GWAS database is an important database for genetic association studies,maintained by international organizations with no country-specific affiliation.The inverse variance weighting method in the two-sample Mendelian randomization method was the main method,and the Bayesian weighted Mendelian randomization method was used to analyze the prior distribution,sample data and weights,which were then used to calculate the posterior distribution.The accuracy and reliability of the inverse variance weighting results were evaluated according to the posterior distribution,supplemented by MR-Egger,weighted median,simple model,and weighted mode methods.The pliotropy test and heterogeneity test were used to ensure the robustness of the process.The results of the inverse variance weighting method were used for subsequent mediating effect analysis.RESULTS AND CONCLUSION:(1)The inverse variance weighting method identified 4 immune cells strongly correlated with hip osteoarthritis,and 20 metabolites strongly associated with hip osteoarthritis,all of which had no reverse causal relationship.At the same time,the validation results of Bayesian weighted Mendelian randomization method showed that the posterior mean value was similar to the estimated value of the inverse variance weighting,and the posterior variance was relatively lower.One monocyte subtype(PDL-1 on CD14-CD16+)was finally screened out to have a causal relationship with hip osteoarthritis,with a total effect of-0.047(odds ratio=0.954,95％confidence interval:0.926-0.983),and a mediating effect of-0.004(odds ratio=0.939,95％confidence interval:0.902-0.978)mediated by alliin levels,accounting for 8.5％of the total effect.It was concluded that alliin is a protective factor in the progression of hip osteoarthritis,in which this metabolite plays a mediating role.(2)The large amount of data from international databases and European population analysis is of great significance to Chinese biomedicine,which can provide clues for research on the genetic susceptibility to similar diseases in the Chinese population,aiding in discovering the unique associations.The pharmacogenomic approaches used can be adapted to screen for drug response genes in the Chinese population,enhancing the precision of personalized medicine.Additionally,the advanced high-throughput technologies and statistical methods employed can be learned and applied to disease prevention and treatment research.

BACKGROUND:Some studies have confirmed the changes in the function of immune cell subsets such as monocytes,T cells,B cells,and natural killer cells(NK cells)in patients with osteoarthritis,but the specific regulatory mechanisms are unclear.OBJECTIVE:To explore the causal relationship between plasma metabolite-mediated immune cells and hip osteoarthritis.METHODS:The Genome-Wide Association Studies(GWAS)data of 731 immune cells were used as the exposure,the GWAS data of hip osteoarthritis were used as the outcome,and 1 400 plasma metabolites were selected as mediating factors.The GWAS database is an important database for genetic association studies,maintained by international organizations with no country-specific affiliation.The inverse variance weighting method in the two-sample Mendelian randomization method was the main method,and the Bayesian weighted Mendelian randomization method was used to analyze the prior distribution,sample data and weights,which were then used to calculate the posterior distribution.The accuracy and reliability of the inverse variance weighting results were evaluated according to the posterior distribution,supplemented by MR-Egger,weighted median,simple model,and weighted mode methods.The pliotropy test and heterogeneity test were used to ensure the robustness of the process.The results of the inverse variance weighting method were used for subsequent mediating effect analysis.RESULTS AND CONCLUSION:(1)The inverse variance weighting method identified 4 immune cells strongly correlated with hip osteoarthritis,and 20 metabolites strongly associated with hip osteoarthritis,all of which had no reverse causal relationship.At the same time,the validation results of Bayesian weighted Mendelian randomization method showed that the posterior mean value was similar to the estimated value of the inverse variance weighting,and the posterior variance was relatively lower.One monocyte subtype(PDL-1 on CD14-CD16+)was finally screened out to have a causal relationship with hip osteoarthritis,with a total effect of-0.047(odds ratio=0.954,95％confidence interval:0.926-0.983),and a mediating effect of-0.004(odds ratio=0.939,95％confidence interval:0.902-0.978)mediated by alliin levels,accounting for 8.5％of the total effect.It was concluded that alliin is a protective factor in the progression of hip osteoarthritis,in which this metabolite plays a mediating role.(2)The large amount of data from international databases and European population analysis is of great significance to Chinese biomedicine,which can provide clues for research on the genetic susceptibility to similar diseases in the Chinese population,aiding in discovering the unique associations.The pharmacogenomic approaches used can be adapted to screen for drug response genes in the Chinese population,enhancing the precision of personalized medicine.Additionally,the advanced high-throughput technologies and statistical methods employed can be learned and applied to disease prevention and treatment research.

BACKGROUND:It has been hypothesized that PANoptosis may be involved in the pathologic process of osteoporosis,but there have been no studies addressing the mechanisms of PANoptosis genes in osteoporosis. OBJECTIVE:To analyze the biological mechanism of PANoptosis regulators in the occurrence and development of osteoporosis. METHODS:The GSE56815 dataset was obtained from the Gene Expression Omnibus database and PANoptosis genes were extracted for differential analysis.The key genes of PANoptosis were screened by random forest tree model to construct a disease risk prediction model.Consensus clustering algorithm,single sample genome enrichment analysis and immune infiltration analysis were used to explore the differences between different PANoptosis molecular subtypes.Herbal drugs that regulate the key genes of PANoptosis were predicted through Coremine medical database,a medical ontology information retrieval platform. RESULTS AND CONCLUSION:Based on the four PANoptosis key genes(CASP1,CASP10,MEFV,and TNF),the diagnostic markers of osteoporosis were determined,and the risk prediction model was constructed and verified.Osteoporosis was divided into two different PANoptosis subtypes(clusters A,B and gene clusters A,B),and the PANoptosis scores of cluster B and gene cluster B were higher than those of cluster A and gene cluster A,respectively.Traditional Chinese drugs such as ginseng which can regulate the key genes of PANoptosis were predicted by the Coremine medical database.

BACKGROUND:The etiology of osteoarthritis is varied and its pathogenesis is still unclear.As bioinformatics has been deepening in recent years,increasing studies have found that the aberrant expression of long non-coding RNAs(lncRNAs)and microRNAs(miRNAs)in joint tissues may mediate the downstream signaling pathways involved in the development of osteoarthritis. OBJECTIVE:To review the mechanism of lncRNA in the development of osteoarthritis and the therapeutic effects of monomers and active compounds derived from traditional Chinese medicine that modulate lncRNA and downstream signaling pathways in osteoarthritis. METHODS:We searched CNKI,WanFang,VIP,and PubMed using the search terms of"long non-coding RNA,knee osteoarthritis,miRNA,chondrocytes,signaling pathway,and traditional Chinese medicine"in Chinese and English,respectively.The search time was from the inception of each database to March 2023.A total of 61 articles were included according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:The pathogenesis of knee osteoarthritis involves a complex molecular regulatory network,including aberrant expression of lncRNAs and miRNAs in cartilage tissues,which may lead to apoptosis of chondrocytes,degradation of cartilage extracellular matrix,and production of large amounts of pro-inflammatory cytokines.These changes interact with each other to cause degeneration of articular cartilage and progression of osteoarthritis.Therefore,further in-depth studies are needed to reveal the fine mechanisms of the molecular regulatory network.The mechanism of traditional Chinese medicine in the treatment of osteoarthritis mainly focuses on regulating the expression of lncRNA and miRNA,thereby alleviating chondrocyte apoptosis and extracellular matrix degradation,promoting cell proliferation,and slowing down the development of osteoarthritis.

Objective To determine whether thyroid hormone (TH) level could also be an independent and incremental predictor of adverse events in patients with hypertrophic cardiomyopathy (HCM).Methods A total of 982 consecutive patients with HCM at the National Center for Cardiovascular Diseases (China) from October 2009 to December 2013 were included in the present study,and followed up till the end of December 2016.The patients were divided into three groups according to the levels of free triiodothyronine (FT3):the group 1 (FT3≤4.28 pmol/L,n=335),the group 2 (FT3＞4.28-＜4.79 pmol/L,n=310),and the group 3 (FT34.79-6.30 pmol/L,n=337).Results After a follow-up period of (53.8 ± 14.1) months,39 patients (4.0％) either suffered death with all causes or received a cardiac transplantation (7.8％,2.9％ and 1.2％ of the patients in the group 1,group 2 and group 3,respectively).A multivariable Cox regression analysis revealed that FT3≤4.28 pmol/L was associated with a significantly higher risk of all-cause mortality or cardiac transplantation (HR 8.83,95％ CI 1.115-69.905,P=0.039) in HCM patients.Conclusions Low levels of FT3 is a risk factor of adverse events for patients with HCM,indicting a role of FT3 as a marker for assessing the risk of long-term adverse events in these patients.

Objective: To determine the value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) on predicting the long-term outcome of patients with hypertrophic cardiomyopathy (HCM) . Methods: NT-proBNP was measured in 831 consecutive patients with HCM at Fuwai Hospital from October 2009 to December 2013 and patients were followed up clinically for (53.3±15.4) months. Patients were divided into 3 groups according to NT-proBNP values: NT-proBNP<860 pmol/L (n=276) , 860 pmol/L≤NT-proBNP≤1 905 pmol/L (n=278) , NT-proBNP>1 905 pmol/L (n=277) . The related baseline data, laboratory examination and echocardiographic results were compared among groups. The primary endpoints of this study were all-cause mortality and cardiac transplantation. Cox proportional hazards model was used to estimate hazard ratio (HR) . Kaplan-Meier analysis was used to evaluate the survival status of patients among the 3 groups. Results: During a median follow-up of (53.3±15.4) months, all-cause mortality or cardiac transplantation occurred in 37 patients (4.5%) , event rate was 1.4% (4/276) , 4.0% (11/278) and 7.9% (22/277) in patients with NT-proBNP<860 pmol/L, 860 pmol/L≤NT-proBNP≤1 905 pmol/L and NT-proBNP>1 905 pmol/L, respectively. Multivariable Cox regression analysis identified that age (HR 1.066, 95%CI 1.027-1.107) and NT-proBNP (HR 1.026, 95% CI 1.010-1.042) were independent predictors of all-cause mortality or cardiac transplantation. Among the 3 groups, the survival rate of the NT-proBNP<860 pmol/L group was the highest,and that of the NT-proBNP>1 905 pmol/L group was the lowest (P<0.01) . Conclusions The level of NT-proBNP provides clinically relevant information for long-term adverse events risk stratification in patients with HCM.