Objective To investigate the clinical features of chronic hepatitis C(CHC)patients with hepatitis C virus genotype 3(HCV GT3)infection and the risk factors for disease progression.Methods A multicenter retrospective cohort study was conducted among 1 002 CHC patients from 11 clinical centers in Northwest China from December 2017 to November 2023,and according to their genotype,they were divided into GT1,GT2,GT3,and GT6 groups.Clinical features were compared between the patients with different genotypes.The one-way analysis of variance was used for comparison of normally distributed continuous data between groups,and the Scheffe test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of data with skewed distribution between groups;the chi-square test or Fisher test was used for comparison of categorical data between groups.The multivariate logistic regression analysis was used to explore the influencing factors for the progression of CHC to liver cirrhosis.Results In terms of the genotype,there were 427 patients with GT1 infection,242 with GT2 infection,299 with GT3 infection(210 patients with GT3a infection,87 with GT3b infection,and 2 with unclassified genotype),and 34 with GT6 infection.The patients with GT3 infection had a significantly younger age than those with GT1 infection(51.3±0.5 years vs 53.2±0.6 years,P<0.05)or GT2 infection(51.3±0.5 years vs 53.7±0.8 years,P<0.05),and for the patients with liver cirrhosis,the patients with GT3 infection had a significantly younger age than those with GT1 infection(52.1±0.5 years vs 59.4±0.9 years,P<0.001)or GT2 infection(52.1±0.5 years vs 58.1±1.1 years,P<0.001).Among the patients with GT3 infection,male patients accounted for 77.9%and the patients with liver cirrhosis accounted for 46.2%,which were significantly higher than those among the patients with GT1,GT2 or GT6 infection(all P<0.001).At baseline,the patients with GT3 infection had significantly higher levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)than those with GT1 or GT2 infection,significantly higher aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB4)than those with GT1,GT2 or GT6 infection,a significantly lower platelet count(PLT)than those with GT2 or GT6 infection,a significantly higher level of alpha-fetoprotein than those with GT2 or GT6 infection,and a significantly lower level of albumin(Alb)than those with GT6 infection(all P<0.05).There were no significant differences between the patients with GT3a infection and those with GT3b infection in age,sex,the proportion of patients with liver cirrhosis,comorbidities,HCV RNA quantification,PLT,ALT,AST,alkaline phosphatase,Alb,APRI,and FIB-4(all P>0.05).The multivariate logistic regression analysis showed that PLT≤150×109/L(odds ratio[OR]=10.72,95%confidence interval[CI]:5.76-35.86,P<0.001)and Alb≤35 g/L(OR=3.74,95%CI:1.22-11.45,P=0.021)were risk factors for liver cirrhosis.Conclusion Most CHC patients with GT3 infection are male in Northwest China,and compared with the patients with other genotypes,such patients tend to have a younger age of onset and higher degrees of liver inflammation activity and fibrosis.Low PLT and a low level of Alb are risk factors for progression to liver cirrhosis in CHC patients with GT3 infection.

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.

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.

Objective To investigate the clinical features of chronic hepatitis C(CHC)patients with hepatitis C virus genotype 3(HCV GT3)infection and the risk factors for disease progression.Methods A multicenter retrospective cohort study was conducted among 1 002 CHC patients from 11 clinical centers in Northwest China from December 2017 to November 2023,and according to their genotype,they were divided into GT1,GT2,GT3,and GT6 groups.Clinical features were compared between the patients with different genotypes.The one-way analysis of variance was used for comparison of normally distributed continuous data between groups,and the Scheffe test was used for further comparison between two groups.The Kruskal-Wallis H test was used for comparison of data with skewed distribution between groups;the chi-square test or Fisher test was used for comparison of categorical data between groups.The multivariate logistic regression analysis was used to explore the influencing factors for the progression of CHC to liver cirrhosis.Results In terms of the genotype,there were 427 patients with GT1 infection,242 with GT2 infection,299 with GT3 infection(210 patients with GT3a infection,87 with GT3b infection,and 2 with unclassified genotype),and 34 with GT6 infection.The patients with GT3 infection had a significantly younger age than those with GT1 infection(51.3±0.5 years vs 53.2±0.6 years,P<0.05)or GT2 infection(51.3±0.5 years vs 53.7±0.8 years,P<0.05),and for the patients with liver cirrhosis,the patients with GT3 infection had a significantly younger age than those with GT1 infection(52.1±0.5 years vs 59.4±0.9 years,P<0.001)or GT2 infection(52.1±0.5 years vs 58.1±1.1 years,P<0.001).Among the patients with GT3 infection,male patients accounted for 77.9%and the patients with liver cirrhosis accounted for 46.2%,which were significantly higher than those among the patients with GT1,GT2 or GT6 infection(all P<0.001).At baseline,the patients with GT3 infection had significantly higher levels of alanine aminotransferase(ALT)and aspartate aminotransferase(AST)than those with GT1 or GT2 infection,significantly higher aspartate aminotransferase-to-platelet ratio index(APRI)and fibrosis-4(FIB4)than those with GT1,GT2 or GT6 infection,a significantly lower platelet count(PLT)than those with GT2 or GT6 infection,a significantly higher level of alpha-fetoprotein than those with GT2 or GT6 infection,and a significantly lower level of albumin(Alb)than those with GT6 infection(all P<0.05).There were no significant differences between the patients with GT3a infection and those with GT3b infection in age,sex,the proportion of patients with liver cirrhosis,comorbidities,HCV RNA quantification,PLT,ALT,AST,alkaline phosphatase,Alb,APRI,and FIB-4(all P>0.05).The multivariate logistic regression analysis showed that PLT≤150×109/L(odds ratio[OR]=10.72,95%confidence interval[CI]:5.76-35.86,P<0.001)and Alb≤35 g/L(OR=3.74,95%CI:1.22-11.45,P=0.021)were risk factors for liver cirrhosis.Conclusion Most CHC patients with GT3 infection are male in Northwest China,and compared with the patients with other genotypes,such patients tend to have a younger age of onset and higher degrees of liver inflammation activity and fibrosis.Low PLT and a low level of Alb are risk factors for progression to liver cirrhosis in CHC patients with GT3 infection.

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.

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.

OBJECTIVE To investigate the effects and potential mechanism of Qiangxin decoction on mitochondrion of rats with chronic heart failure(CHF).METHODS The CHF model was established by ligating the left anterior descending branch of the coronary artery.Modeled rats were divided into model group,Qiangxin decoction low-dose and high-dose groups(12.25,24.50 g/kg,calculated by crude drug),and chemical medicine group(Sacubitril valsartan sodium tablets,10.42 mg/kg),with 10 rats in each group;control group was set up without treatment.Each group of rats was orally administered with the corresponding medication or normal saline twice a day for 28 consecutive days.After the last medication,the contents of N-terminal pro-brain natriuretic peptide(NT-proBNP)and adenosine triphosphate(ATP)in serum and phosphatidic acid(PA)and cardiolipin(CL)in myocardial tissue were all detected;the pathological damage and collagen fibrosis of rat myocardial tissue were observed;the apoptosis of myocardial cells was determined;the ultrastructure of myocardial tissue was observed;the protein expressions of mitofusin 1(Mfn1),Mfn2,optic atrophy protein 1(OPA1)and dynamin-related protein 1(Drp1)were all detected in myocardial tissue.RESULTS Compared with control group,the serum content of NT-proBNP,apoptotic rate of myocardial cells,and relative expressions of S-OPA1 and Drp1 proteins were all increased significantly;serum content of ATP,contents of PA and CL,and relative expressions of Mfn1,Mfn2 and L-OPA1 proteins were all significantly reduced(P＜0.05).There were abnormal membrane tissue structure in various layers of myocardial tissue,degeneration and necrosis of myocardial cells,and severe fibrosis;the mitochondria were swollen,with reduced or absent cristae,and uneven matrix density.After intervention with Qiangxin decoction,the levels of the aforementioned quantitative indicators in serum and myocardial tissue of rats(excluding CL content in the Qiangxin decoction low-dose group)were significantly reversed(P＜0.05);the pathological damage of myocardial tissue had significantly improved,fibrosis had significantly reduced,mitochondrial morphology tended to be normal,cristae had increased,and matrix density was uniform.CONCLUSIONS Qiangxin decoction can regulate myocardial mitochondrial function and structural integrity of CHF rats,thereby improving myocardial energy metabolism and antagonizing myocardial fibrosis,the mechanism of which may be associated with activating PA/Mfn/CL signaling pathway.

Objective To evaluate the causal relationship between blood metabolites and hypertensive heart disease(HHD)using two-sample bidirectional Mendelian randomization(MR)analysis.Methods HHD data were obtained from the Genome-wide Associ-ation Study(GWAS)database.A GW AS containing 1400 blood metabolites was used as an exposure factor,and single nucleotide poly-morphism(SNP)significantly associated with exposure factors were selected as instrumental variable(IV).The causal relationship be-tween 1400 blood metabolites and HHD was analyzed by'TwoSampleMR'and'gwasglue'packages of R software(V4.3.2).MR-Eggeer regression method,weighted median(WM)method,and inverse variance weighting(IVW)method and other methods were used.And a series of verification analyses such as heterogeneity,pleiotropic,and sensitivity and so on were performed.Finally,reverse MR a-nalysis was performed.Results IVW analysis of the causal relationship between 1400 blood metabolites and HHD showed that deoxychol-ic acid glucuronic(OR=0.847,95％CI:0.770-0.931)was a protective factor,and the risk of HHD decreased with the increase of this metabolite.Butyric/isobutyric(4∶0)(OR=1.316,95％CI:1.134-1.528)was a risk factor.With the increase of metabolites,the risk of HHD increased.Conclusion Butyric/isobutyric(4∶0)had effect of promoting HHD,and deoxycholic acid glucuronide had effect of inhibiting HHD.This may be a new idea and new basis for the future research and treatment of HHD.