BACKGROUND:Studies at home and abroad have shown that sarcopenia is closely related to metabolites.At present,the relationship between the latest 1400 blood metabolites and sarcopenia is still unknown.OBJECTIVE:To analyze the causal relationship between 1 400 metabolites and sarcopenia and its relevance with cardiovascular disease using Mendelian randomization.METHODS:Genome-wide association study(GWAS)data of sarcopenia-related characteristics(grip strength,limb muscle lean body mass,and walking speed)were obtained from the OPEN GWAS website as outcome data.A GWAS containing 1 400 metabolites was used as an exposure factor,and single nucleotide polymorphisms significantly associated with exposure factors were selected as instrumental variables.The causal association between 1 400 metabolites and sarcopenia was analyzed by"TwoSampleMR"and"gwasglue"packages of R software(V4.3.2).The research methods included inverse variance weighting,MR-Eggeer regression intercept,weighted median method,and simple mode.Heterogeneity,pleiotropic,sensitivity and other verification analysis were performed.Finally,reverse Mendelian randomization analysis was performed.RESULTS AND CONCLUSION:(1)The causal relationship between 1 400 serum metabolites and sarcopenia was analyzed by inverse variance weighting.The results showed that 1-linoleoyl-2-linoleoyl-GPC(18:2/18:3)and glycodeoxycholate 3-sulfate were protective factors,and the risk of disease decreased with the increase of metabolites(P＜0.01).(2)Two unknown metabolites(X-12822 and X-15486)and trans-3,4-methyleneheptanoate were risk factors.With the increase of two unknown metabolites(X-12822 and X-15486),the degree of low grip strength of male hands increased.Similarly,with the increase of trans-3,4-methylene heptanoate,the risk of disease also increased(P＜0.01).(3)To conclude,1-linoleoyl-2-linoleoyl-GPC(18:2/18:3)and glycodeoxycholate 3-sulfate have inhibitory effects on sarcopenia.Two unknown metabolites(X-12822 and X-15486)and trans-3,4-methyleneheptanoate can promote sarcopenia.This may be a new idea and new basis for sarcopenia research and treatment in the future.This study will also provide a reference for the study of the role of related metabolites in the Chinese population.

BACKGROUND:Observations from several clinical studies suggest a close relationship between hypertension and osteoporosis,but the causal relationship between hypertension and osteoporosis is unclear. OBJECTIVE:To determine whether there is a causal relationship between hypertension and osteoporosis,multisite bone mineral density and osteoporosis with fractures in Asian and European populations,respectively,using a comprehensive two-sample Mendelian randomized analysis. METHODS:Data of osteoporosis in Asian populations were obtained through Japan biological bank. Data of osteoporosis in European populations were obtained from UK Biobank,a British biological bank. Data of hypertension,multisite bone mineral density and osteoporosis with fractures were all from FinnGen R10 database. Inverse variance weighted method,MR-Egger regression method,weighted median method,weighted model method and simple model method were used to study the causal relationship between hypertension and osteoporosis,multisite bone mineral density and osteoporosis with fracture in Asian and European populations. Comprehensive sensitivity analysis was used to verify the robustness,heterogeneity and level pleiotropy of the results. Stsiger test was used to determine whether there was a reverse causal relationship between osteoporosis and hypertension. RESULTS AND CONCLUSION:In Asian populations,there was no significant genetic predictive causal relationship between hypertension and osteoporosis,and there was a positive causal relationship between hypertension and calcaneal bone mineral density. In European populations,hypertension had a negative causal relationship with osteoporosis,and there was no significant causal relationship between hypertension and systemic bone mineral density,calcaneal bone mineral density,forearm bone mineral density and osteoporosis with fracture. According to the stsiger test,there was no reverse causal relationship between osteoporosis,multiplesite bone mineral density,osteoporosis with fracture and hypertension in Asian and European populations. These results indicate that there is a causal relationship between hypertension and osteoporosis,that is,in Asian populations,hypertension and calcaneal bone mineral density show a positive causal relationship;in European populations,hypertension and osteoporosis show a negative causal relationship,but no reverse causal relationship.

BACKGROUND:The relationship between rheumatoid arthritis and coronary atherosclerosis has received extensive attention.Inflammation is related to rheumatoid arthritis and coronary atherosclerosis,indicating that there may be a common pathophysiological pathway between the two diseases.However,observational studies have not yet clarified the causal relationship.OBJECTIVE:To explore whether there is a causal relationship between rheumatoid arthritis and coronary atherosclerosis,as well as the potential causal relationship with 1 400 serum metabolites and 91 inflammatory factors through a Mendelian randomization analysis.METHODS:Coronary atherosclerosis data are from Finngen database,rheumatoid arthritis data are from IEU OpenGWAS database,serum metabolites data are from Canadian Longitudinal Study on Aging,Augsburg Cooperative Health Research and British Twin Project Research,and data of 91 inflammatory proteins are from research published in Nature Immunology in 2023.Mendelian randomization analysis was performed using data from genome-wide association studies,and causal effects were evaluated using inverse variance weighting,MR-Egger regression,weighted median,weighted model,and simple model methods,with inverse variance weighting being the primary analysis method.To enhance robustness,Cochran's Q-test MR-Egger intercept was used for sensitivity analysis.RESULTS AND CONCLUSION:(1)Inverse variance weighting results showed that rheumatoid arthritis was positively correlated with the increased relative risk of coronary atherosclerosis(odds ratio=1.002,95％confidence interval=1.001-1.003,P=0.003).There was no reverse causal relationship between coronary atherosclerosis and rheumatoid arthritis.In addition,96 serum metabolites and 9 inflammatory factors were found to have causal relationships with coronary atherosclerosis.There was a causal relationship between 51 serum metabolites and 7 inflammatory factors and rheumatoid arthritis.(2)This study provided epidemiological evidence between rheumatoid arthritis and coronary atherosclerosis,and emphasized the potential role of serum metabolites and inflammatory factors in the pathogenesis of these diseases.These findings may contribute to the development of new treatment strategies.Due to the limited inclusion of data from Asian populations,most contemporary studies used international databases and European population analyses.By collecting and analyzing the health data of European populations,it is conducive to a better understanding of the effects and potential role of Chinese medicine in Europe,and to further promote the practice of modern integration of Western and Chinese medicine.Meanwhile,through the comparative study with the European databases,it is possible to reveal the genetic differences and susceptibility to diseases among different populations,providing more dimensions and perspectives for global health research.

BACKGROUND:Observations from several clinical studies suggest a close relationship between hypertension and osteoporosis,but the causal relationship between hypertension and osteoporosis is unclear. OBJECTIVE:To determine whether there is a causal relationship between hypertension and osteoporosis,multisite bone mineral density and osteoporosis with fractures in Asian and European populations,respectively,using a comprehensive two-sample Mendelian randomized analysis. METHODS:Data of osteoporosis in Asian populations were obtained through Japan biological bank. Data of osteoporosis in European populations were obtained from UK Biobank,a British biological bank. Data of hypertension,multisite bone mineral density and osteoporosis with fractures were all from FinnGen R10 database. Inverse variance weighted method,MR-Egger regression method,weighted median method,weighted model method and simple model method were used to study the causal relationship between hypertension and osteoporosis,multisite bone mineral density and osteoporosis with fracture in Asian and European populations. Comprehensive sensitivity analysis was used to verify the robustness,heterogeneity and level pleiotropy of the results. Stsiger test was used to determine whether there was a reverse causal relationship between osteoporosis and hypertension. RESULTS AND CONCLUSION:In Asian populations,there was no significant genetic predictive causal relationship between hypertension and osteoporosis,and there was a positive causal relationship between hypertension and calcaneal bone mineral density. In European populations,hypertension had a negative causal relationship with osteoporosis,and there was no significant causal relationship between hypertension and systemic bone mineral density,calcaneal bone mineral density,forearm bone mineral density and osteoporosis with fracture. According to the stsiger test,there was no reverse causal relationship between osteoporosis,multiplesite bone mineral density,osteoporosis with fracture and hypertension in Asian and European populations. These results indicate that there is a causal relationship between hypertension and osteoporosis,that is,in Asian populations,hypertension and calcaneal bone mineral density show a positive causal relationship;in European populations,hypertension and osteoporosis show a negative causal relationship,but no reverse causal relationship.

BACKGROUND:The relationship between rheumatoid arthritis and coronary atherosclerosis has received extensive attention.Inflammation is related to rheumatoid arthritis and coronary atherosclerosis,indicating that there may be a common pathophysiological pathway between the two diseases.However,observational studies have not yet clarified the causal relationship.OBJECTIVE:To explore whether there is a causal relationship between rheumatoid arthritis and coronary atherosclerosis,as well as the potential causal relationship with 1 400 serum metabolites and 91 inflammatory factors through a Mendelian randomization analysis.METHODS:Coronary atherosclerosis data are from Finngen database,rheumatoid arthritis data are from IEU OpenGWAS database,serum metabolites data are from Canadian Longitudinal Study on Aging,Augsburg Cooperative Health Research and British Twin Project Research,and data of 91 inflammatory proteins are from research published in Nature Immunology in 2023.Mendelian randomization analysis was performed using data from genome-wide association studies,and causal effects were evaluated using inverse variance weighting,MR-Egger regression,weighted median,weighted model,and simple model methods,with inverse variance weighting being the primary analysis method.To enhance robustness,Cochran's Q-test MR-Egger intercept was used for sensitivity analysis.RESULTS AND CONCLUSION:(1)Inverse variance weighting results showed that rheumatoid arthritis was positively correlated with the increased relative risk of coronary atherosclerosis(odds ratio=1.002,95％confidence interval=1.001-1.003,P=0.003).There was no reverse causal relationship between coronary atherosclerosis and rheumatoid arthritis.In addition,96 serum metabolites and 9 inflammatory factors were found to have causal relationships with coronary atherosclerosis.There was a causal relationship between 51 serum metabolites and 7 inflammatory factors and rheumatoid arthritis.(2)This study provided epidemiological evidence between rheumatoid arthritis and coronary atherosclerosis,and emphasized the potential role of serum metabolites and inflammatory factors in the pathogenesis of these diseases.These findings may contribute to the development of new treatment strategies.Due to the limited inclusion of data from Asian populations,most contemporary studies used international databases and European population analyses.By collecting and analyzing the health data of European populations,it is conducive to a better understanding of the effects and potential role of Chinese medicine in Europe,and to further promote the practice of modern integration of Western and Chinese medicine.Meanwhile,through the comparative study with the European databases,it is possible to reveal the genetic differences and susceptibility to diseases among different populations,providing more dimensions and perspectives for global health research.

Objective:To investigate the influence of ultrasonic monitoring of bladder filling levels on setup errors before fractionated radiotherapy for cervical cancer patients through a comparative analysis, and its effectiveness in improving clinical target volume (CTV) margins.Methods:A retrospective study was conducted on 1 284 error data of setup via cone beam CT (CBCT) and 6D setup error correction system from 172 cervical cancer patients treated in the Radiotherapy Department of Peking University Cancer Hospital from January 2019 to October 2023. These patients were classified into two groups: 87 (659 times of setup) with ultrasonic monitoring of bladder filling levels and 85 (625 times of setup) without ultrasonic monitoring. The setup errors, error distributions, and numbers of abnormal setups between the two groups were compared in the lateral (Lat), longitudinal (Lng), vertical (Vrt), pitch (Pitch), roll (Roll), and rotational (Rtn) dimensions. Moreover, the CTV to planning target volume(PTV) margin values in the three-dimensional direction were calculated for both groups to assess the clinical value of ultrasonic monitoring of bladder filling levels before fractionated radiotherapy.Results:Compared to the group without ultrasonic monitoring, the group with ultrasonic monitoring exhibited lower median values of setup errors in all six-dimensional directions and smaller upper and lower interquartile ranges ( Z = -10.86 to -6.34, P<0.05). The group with ultrasonic monitoring manifested more concentrated setup errors in various directions and statistically significantly reduced numbers of abnormal setups ( χ2=15.33, P<0.05). Moreover, CTV-PTV margins of the group with ultrasonic monitoring displayed reduced CTV-PTV margin values by 0.55, 1.52, and 1.26 mm in the Vrt, Lng, and Lat directions, respectively. Conclusions:Pre-radiotherapy ultrasonic monitoring of bladder filling levels in cervical cancer patients can significantly improve the repeatability of setup, thus notably reducing the incidence of abnormal setups. Theoretically, it can narrow the range from the CTV to the PTV, thereby minimizing radiation exposure to healthy tissues and ultimately enhancing radiotherapy precision for cervical cancer and reducing radiation damage.

Objective To utilize a comprehensive two-sample Mendelian randomized analysis for determining the causal relation-ship between immune cells and heart failure.Methods Immune cell data were collected from the genome-wide association analysis da-tabase,while the data of heart failure were obtained from the FinnGen database.The inverse variance weighted method,MR-Egger re-gression method,weighted median method,and weighted model method were employed to analyze the causal relationship between immune cells and heart failure.Comprehensive sensitivity analysis was utilized to verify the robustness,heterogeneity,and level pleiotropy of the results.The Stsiger test was applied to determine whether there was a reverse causal relationship between heart failure and immune cells.Results A total of 2557single nucleotide polymorphisms(SNP)were obtained from 731 immune cells.A total of 25 immunophenotypes were identified as having a causal function before the adjustment.After Bonferroni adjustment,only three results retained statistical signifi-cance.The inverse variance weighted analysis showed that there was a significant causal relationship between the absolute lymphocyte count and the increased risk of heart failure(HF)(OR=1.199,95％CI:1.104-1.302,P=1.70 × 10-5).The absolute count of T cells(OR=1.186,95％CI:1.095-1.284,P=2.84×10-5),and the absolute count of plasma-like dendritic cells(OR=1.137,95％CI:1.056-1.224,P=0.0007)were positively correlated with HF.The Stsiger test did not detect a causal relationship between heart failure and immune cells.Conclusion There exists a causal relationship between immune cells and the risk of heart failure.

BACKGROUND:Studies at home and abroad have shown that sarcopenia is closely related to metabolites.At present,the relationship between the latest 1400 blood metabolites and sarcopenia is still unknown.OBJECTIVE:To analyze the causal relationship between 1 400 metabolites and sarcopenia and its relevance with cardiovascular disease using Mendelian randomization.METHODS:Genome-wide association study(GWAS)data of sarcopenia-related characteristics(grip strength,limb muscle lean body mass,and walking speed)were obtained from the OPEN GWAS website as outcome data.A GWAS containing 1 400 metabolites was used as an exposure factor,and single nucleotide polymorphisms significantly associated with exposure factors were selected as instrumental variables.The causal association between 1 400 metabolites and sarcopenia was analyzed by"TwoSampleMR"and"gwasglue"packages of R software(V4.3.2).The research methods included inverse variance weighting,MR-Eggeer regression intercept,weighted median method,and simple mode.Heterogeneity,pleiotropic,sensitivity and other verification analysis were performed.Finally,reverse Mendelian randomization analysis was performed.RESULTS AND CONCLUSION:(1)The causal relationship between 1 400 serum metabolites and sarcopenia was analyzed by inverse variance weighting.The results showed that 1-linoleoyl-2-linoleoyl-GPC(18:2/18:3)and glycodeoxycholate 3-sulfate were protective factors,and the risk of disease decreased with the increase of metabolites(P＜0.01).(2)Two unknown metabolites(X-12822 and X-15486)and trans-3,4-methyleneheptanoate were risk factors.With the increase of two unknown metabolites(X-12822 and X-15486),the degree of low grip strength of male hands increased.Similarly,with the increase of trans-3,4-methylene heptanoate,the risk of disease also increased(P＜0.01).(3)To conclude,1-linoleoyl-2-linoleoyl-GPC(18:2/18:3)and glycodeoxycholate 3-sulfate have inhibitory effects on sarcopenia.Two unknown metabolites(X-12822 and X-15486)and trans-3,4-methyleneheptanoate can promote sarcopenia.This may be a new idea and new basis for sarcopenia research and treatment in the future.This study will also provide a reference for the study of the role of related metabolites in the Chinese population.

Objective To explore the impact of Qiangxin Tang on myocardial fibrosis in rats with chronic heart failure by mediating myocardial mitochondrial autophagy through the Bcl-2/adenovirus E1B 19kDa interacting protein 3/NIP3 like protein X and FUN14domain-containing protein 1.Methods Forty Sprague Dawley rats were divided into five groups randomly by the random number table:sham operation group,model group,Qiangxin Tang group,Captopril group,and Qiangxin Tang+Captopril group,with a total of eight rats in each group.Only the sham operation group threaded without ligating the left coronary artery of the heart.In all the other groups,CHF rat models were established after myocardial infarction by ligating the left coronary artery of the heart.From the day after successful modeling,each group was given corresponding drugs by gavage,and the left ventricular myocardial tissue of each group was de-tected.Western blot was used to detect the expression of NIX,BNIP3,and FUNDC1 proteins in each group.ELISA was used to detect brain natriuretic peptide and cardiac troponin T level.Mitochondrial morphology was observed under transmission electron microscopy.Masson staining was used to observe left ventricular myocardial fibrosis.Results Compared with the sham surgery group,the expression of NIX,BNIP3 and FUNDC1 proteins in the model group was significantly reduced,while the levels of BNP and cTnT were significantly increased(P＜0.05).The left ventricular myocardial tissue showed significant fibrosisand mitochondrial swelling.Compared with the model group,the expression of NIX,BNIP3,and FUNDC1 proteins was significantly increased in Qiangxin Tang group and Captopril group,while the levels of BNP and cTnT were significantly decreased(P＜0.05).The left ventricular myocardial tissue fibrosis was sig-nificantly reduced,and the mitochondrial morphology was mildly altered.Compared with Qiangxin Tang group and Captopril group,the Qiangxin Tang+Captopril group showed significant improvement in the above indicators,and there was no significant difference in the in-dicators between Qiangxin Tang group and Captopril group.Conclusion Qiangxin Tang may promote mitochondrial autophagy and ensure the morphology and function of mitochondrial by upregulating the expression of NIX,BNIP3 and FUNDC1,thereby reducing myocardial injury and fibrosis.In addition,the combination of Qiangxin Tang and Captopril has a better therapeutic effect on CHF.

Objective To utilize a comprehensive two-sample Mendelian randomized analysis for determining the causal relation-ship between immune cells and heart failure.Methods Immune cell data were collected from the genome-wide association analysis da-tabase,while the data of heart failure were obtained from the FinnGen database.The inverse variance weighted method,MR-Egger re-gression method,weighted median method,and weighted model method were employed to analyze the causal relationship between immune cells and heart failure.Comprehensive sensitivity analysis was utilized to verify the robustness,heterogeneity,and level pleiotropy of the results.The Stsiger test was applied to determine whether there was a reverse causal relationship between heart failure and immune cells.Results A total of 2557single nucleotide polymorphisms(SNP)were obtained from 731 immune cells.A total of 25 immunophenotypes were identified as having a causal function before the adjustment.After Bonferroni adjustment,only three results retained statistical signifi-cance.The inverse variance weighted analysis showed that there was a significant causal relationship between the absolute lymphocyte count and the increased risk of heart failure(HF)(OR=1.199,95％CI:1.104-1.302,P=1.70 × 10-5).The absolute count of T cells(OR=1.186,95％CI:1.095-1.284,P=2.84×10-5),and the absolute count of plasma-like dendritic cells(OR=1.137,95％CI:1.056-1.224,P=0.0007)were positively correlated with HF.The Stsiger test did not detect a causal relationship between heart failure and immune cells.Conclusion There exists a causal relationship between immune cells and the risk of heart failure.