ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure （CHF） due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β₁ （TGF-β₁）/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction （HFrEF） and heart failure with mildly reduced ejection fraction （HFmrEF） were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets， sacubitril-valsartan sodium tablets， metoprolol succinate， and spironolactone， and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance， New York Heart Association （NYHA） heart function grade， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， angiotensin Ⅱ （Ang Ⅱ）， left ventricular ejection fraction （LVEF）， left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， interventricular septum thickness at diastole （IVSd）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular shortening fraction （FS）， miR-423-5p， Smad7， Smad2， Smad3， Smad4， TGF-β₁， Ang Ⅱ， type Ⅰ collagen （Col Ⅰ）， type Ⅲ collagen （Col Ⅲ）， mRNA levels of fibronectin （Fn） and α-smooth muscle actin （α-SMA） in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment， both groups showed declined levels of NT-proBNP， Ang Ⅱ， miR-423-5p， Smad2， Smad3， Smad4， TGF-β₁， Col Ⅰ， Col Ⅲ， and mRNA levels of Fn and α-SMA （P0.05）， and the levels of the indicators above were lower in the observation group than in the control group （P0.05）. After treatment， the Smad7 level increased obviously in both groups （P0.05） and was higher in the observation group than in the control group （P0.05）. After treatment， both groups showed decreased MLHFQ scores and increased 6-min walking distance （P0.05）， and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group （P0.05）. After treatment， the control group showed increased LVEF and FS （P0.05） and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS （P0.05）. Moreover， the observation group had lower LVIDd and LVIDs （P0.05） and higher LVEF and FS （P0.05） than the control group. The total response rate of cardiac function in the observation group was 90.38% （47/52）， which was higher than that （70.59%， 36/51） in the control group （P0.05）. No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function， exercise tolerance， and quality of life， regulate neuroendocrine factors， and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF （syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β₁/Smads axis， inhibiting α-SMA and Fn expression， and alleviating myocardial fibrosis. It is worthy of further study.

ObjectiveTo investigate the clinical effect of Ershen Zhenwu Decoction on chronic heart failure （CHF） due to heart-kidney Yang deficiency and blood stasis and its regulatory effects on miR-423-5p/Smad7/transforming growth factor-β₁ （TGF-β₁）/Smads axis and myocardial fibrosis indicators. MethodsOne hundred and fourteen patients with heart failure with reduced ejection fraction （HFrEF） and heart failure with mildly reduced ejection fraction （HFmrEF） were randomly allocated into a control group and an observation group. The control group was treated with dapagliflozin tablets， sacubitril-valsartan sodium tablets， metoprolol succinate， and spironolactone， and the observation group was treated with Ershen Zhenwu Decoction on the basis of the therapy in the control group. The course of treatment was 8 weeks in both groups. The 6-min walking distance， New York Heart Association （NYHA） heart function grade， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， angiotensin Ⅱ （Ang Ⅱ）， left ventricular ejection fraction （LVEF）， left ventricular end-diastolic diameter （LVIDd）， left ventricular end-systolic diameter （LVIDs）， interventricular septum thickness at diastole （IVSd）， left ventricular end-diastolic posterior wall thickness （LVPWd）， left ventricular shortening fraction （FS）， miR-423-5p， Smad7， Smad2， Smad3， Smad4， TGF-β₁， Ang Ⅱ， type Ⅰ collagen （Col Ⅰ）， type Ⅲ collagen （Col Ⅲ）， mRNA levels of fibronectin （Fn） and α-smooth muscle actin （α-SMA） in the myocardial tissue were observed before and after treatment in both groups to evaluate the efficacy of cardiac function and drug safety. ResultsAfter treatment， both groups showed declined levels of NT-proBNP， Ang Ⅱ， miR-423-5p， Smad2， Smad3， Smad4， TGF-β₁， Col Ⅰ， Col Ⅲ， and mRNA levels of Fn and α-SMA （P0.05）， and the levels of the indicators above were lower in the observation group than in the control group （P0.05）. After treatment， the Smad7 level increased obviously in both groups （P0.05） and was higher in the observation group than in the control group （P0.05）. After treatment， both groups showed decreased MLHFQ scores and increased 6-min walking distance （P0.05）， and the observation group had lower MLHFQ score and longer 6-min walking distance than the control group （P0.05）. After treatment， the control group showed increased LVEF and FS （P0.05） and the observation group showcased decreased LVIDd and LVIDs and increased LVEF and FS （P0.05）. Moreover， the observation group had lower LVIDd and LVIDs （P0.05） and higher LVEF and FS （P0.05） than the control group. The total response rate of cardiac function in the observation group was 90.38% （47/52）， which was higher than that （70.59%， 36/51） in the control group （P0.05）. No adverse reactions associated with Ershen Zhenwu Decoction were observed during the study period. ConclusionErshen Zhenwu Decoction can improve the cardiac function， exercise tolerance， and quality of life， regulate neuroendocrine factors， and slow down/reverse myocardial remodeling in the patients with HFrEF and HFmrEF （syndrome of heart-kidney Yang deficiency and blood stasis by regulating the miR-423-5p/Smad7/TGF-β₁/Smads axis， inhibiting α-SMA and Fn expression， and alleviating myocardial fibrosis. It is worthy of further study.

Objective To observe the value of preoperative magnetization transfer imaging(MTI)for predicting postoperative pancreatic fistula(POPF)after distal pancreatectomy(DP).Methods A total of 65 patients with pancreatic tumor who underwent DP and preoperative MR scanning were retrospectively enrolled and divided into clinically relevant POPF(CR-POPF)group(n=14,with grade B or C fistula),biochemical fistula group(n=31,postoperative drain fluid amylase level exceeding 3 times the upper limit of normal)and non-fistula group(n=20,postoperative drain fluid amylase level not exceeding 3 times the upper limit of normal)based on postoperative records.Clinical data and magnetization transfer ratio(MTR)of pancreatic tissue at the surgical margin were compared among 3 groups.The predictive value of MTR for CR-POPF was evaluated according to the area under the curve(AUC)of receiver operating characteristic(ROC)curve.Results Patients' age,intraoperative blood loss and the proportion of pancreatic ductal adenocarcinoma in both CR-POPF group and biochemical fistula group were lower than those in non-fistula group(all adjusted P＜0.05),while no significant difference was found between the former two groups(all adjusted P＞0.05).MTR of pancreatic tissue at the surgical margin in CR-POPF group was lower than that in both biochemical fistula group and non-fistula group(both P＜0.05),whereas no statistical difference was detected between the latter two groups(P＞0.05).The AUC of MTR for predicting CR-POPF after DP was 0.727.Conclusion Preoperative MTI could be used to predict POPF after DP.

Objective To explore potential association between sedentary time and the risk of all-cause mortality and cardiovascular disease(CVD)in Chinese population using data from the Prospective Urban Rural Epidemiology(PURE-China)cohort study.Methods Baseline data were collected,from 2022 standardized questionnaires and physical examinations,with follow-up until August 31,2022.The primary endpoints were all-cause mortality and cardiovascular events(non-fatal myocardial infarction,stroke or heart failure).Multivariable Cox shared frailty model was used to analyze the association between sedentary time and the risks of all-cause mortality and CVD in the target population,and to compare differences across subgroups based on gender,age and geographic location.Results A total of 47 931 participants were recruited,and 43 367 were included in the final analysis.Over a me-dian follow-up of 11.9±3.0 years,2 277 participants experienced all-cause mortality,3 551 experienced cardiovas-cular events.The Cox model indicated that,compared to individuals with less than 4 h of sedentary time per day,those with 6-8 h had a 23％increased in risk of all-cause mortality(HR=1.23,95％CI:1.06-1.44)and an 18％increased risk of CVD(HR=1.18,95％CI:1.04-1.33).For individuals with more than 8 h of sedentary time,the risk increased by 50％for all-cause mortality(HR=1.50,95％CI:1.16-1.94)and 44％for CVD(HR=1.44,95％CI:1.16-1.79).These associations were more pronounced in men and individuals aged 50 years and older.Conclusions Sedentary behavior is associated with an increased risk of all-cause mortality and cardiovascular disease in Chinese population,especially in the population with sedentary time of 6 hrs or more per day.Reducing sedentary time and increasing physical activity is an important strategy to mitigate the disease burden of cardiovascular disease and premature death.

Immune checkpoint inhibitors(ICIs)have revolutionized cancer therapy,but their use is frequently complicated by immune-related adverse events(irAEs),which often require management with corticosteroids or additional immunosuppressive agents.The prognostic impact of these therapeutic strategies in the setting of irAEs has not been systematically elucidated.This systematic review and meta-analysis aimed to evaluate the impact of corticosteroid(CS)and second-line immunosuppressant(IM)use on survival outcomes among patients who developed irAEs during ICI therapy.Following a preregistered protocol(PROSPERO CRD1144835),we systematically searched PubMed,Embase,Web of Science,Cochrane Library,SinoMed,CNKI and Wanfang to identify studies published in the past 10 years(up to May 2025)reporting on the association between CS and IM use and survival outcomes in ICI-treated patients with irAEs.Two reviewers independently performed study selection,data extraction,and quality assessment.Meta-analyses were performed using R software.A total of 11 studies comprising 7 255 patients were included.Meta-analysis showed that CS use versus no use was not significantly associated with overall survival(OS)(HR=0.73,95%CI:0.45-1.18)or progression-free survival(PFS)(HR=0.68,95%CI:0.00-98.01).For post-irAE survival outcomes,higher cumulative CS dose(per 1 000 mg increment)was associated with a mild protective effect on post-irAE OS(HR=0.95,95%CI:0.92-0.98)and post-irAE PFS(HR=0.96,95%CI:0.94-0.99).In contrast to CS alone,IM use in combination with CS was associated with significantly increased risk of disease progression or death for post-irAE OS(HR=1.40,95%CI:1.11-1.76)and post-irAE PFS(HR=1.32,95%CI:1.08-1.62).Sensitivity analyses demonstrated good robustness of the main significant results.Current evidence suggests that CS and IM management strategies may differentially affect survival outcomes in patients with irAEs following ICI therapy.Increased cumulative CS dose is not associated with worse outcomes,whereas the addition of second-line IMs may increase the risk of adverse survival outcomes.Further prospective studies are warranted to optimize irAE management strategies and to balance the risks of immunosuppressive therapy with anticancer efficacy.

Objective To explore the potential impact of unhealthy diets on cardiovascular diseases and all-cause mortality.Methods This study included the individuals aged 35-70 years from 45 cities and 70 rural communities across 12 provinces in China,as part of the Prospective Urban Rural Epidemiology(PURE)study.Dietary habits were assessed using a food frequency questionnaire.The dietary health status was scored using the Alternative Healthy Eating Index(AHEI),with participants in the lowest tertile of AHEI being categorized into the unhealthy diet group,while others were classified as the healthy diet group.The primary endpoints included major cardiovas-cular diseases(myocardial infarction,stroke,or heart failure)and all-cause mortality.Cox proportional hazard models were used to estimate hazard ratios(HR)for each group.Results A total of 40 925 participants were in-cluded in the study,with a median follow-up time of 11.9 years(interquartile range 9.6-12.6 years).During this period,2 066 deaths and 3 099 cases of major cardiovascular diseases were reported.The results showed that un-healthy diet increased the risk of major cardiovascular diseases by 10%(HR=1.10,95%CI:1.02-1.20,P＜0.05)and all-cause mortality by 7%(HR=1.07,95%CI:1.00-1.18,P＜0.05).Among male residents,un-healthy diet did not increase the risk of major cardiovascular diseases or all-cause mortality.However,among female residents,those with an unhealthy diet had a higher risk of major cardiovascular diseases(HR=1.12,95%CI:1.00-1.25,P＜0.05)and all-cause mortality(HR=1.26,95%CI:1.08-1.46,P＜0.05)compared to those with a healthy diet.Conclusions Unhealthy diet increases the risk of major cardiovascular diseases and all-cause mortality,particularly among women.There is a need to raise awareness about healthy dietary to prevent death and the occurrence of major cardiovascular diseases.

Immune checkpoint inhibitors(ICIs)have revolutionized cancer therapy,but their use is frequently complicated by immune-related adverse events(irAEs),which often require management with corticosteroids or additional immunosuppressive agents.The prognostic impact of these therapeutic strategies in the setting of irAEs has not been systematically elucidated.This systematic review and meta-analysis aimed to evaluate the impact of corticosteroid(CS)and second-line immunosuppressant(IM)use on survival outcomes among patients who developed irAEs during ICI therapy.Following a preregistered protocol(PROSPERO CRD1144835),we systematically searched PubMed,Embase,Web of Science,Cochrane Library,SinoMed,CNKI and Wanfang to identify studies published in the past 10 years(up to May 2025)reporting on the association between CS and IM use and survival outcomes in ICI-treated patients with irAEs.Two reviewers independently performed study selection,data extraction,and quality assessment.Meta-analyses were performed using R software.A total of 11 studies comprising 7 255 patients were included.Meta-analysis showed that CS use versus no use was not significantly associated with overall survival(OS)(HR=0.73,95%CI:0.45-1.18)or progression-free survival(PFS)(HR=0.68,95%CI:0.00-98.01).For post-irAE survival outcomes,higher cumulative CS dose(per 1 000 mg increment)was associated with a mild protective effect on post-irAE OS(HR=0.95,95%CI:0.92-0.98)and post-irAE PFS(HR=0.96,95%CI:0.94-0.99).In contrast to CS alone,IM use in combination with CS was associated with significantly increased risk of disease progression or death for post-irAE OS(HR=1.40,95%CI:1.11-1.76)and post-irAE PFS(HR=1.32,95%CI:1.08-1.62).Sensitivity analyses demonstrated good robustness of the main significant results.Current evidence suggests that CS and IM management strategies may differentially affect survival outcomes in patients with irAEs following ICI therapy.Increased cumulative CS dose is not associated with worse outcomes,whereas the addition of second-line IMs may increase the risk of adverse survival outcomes.Further prospective studies are warranted to optimize irAE management strategies and to balance the risks of immunosuppressive therapy with anticancer efficacy.

Objective To explore the potential impact of unhealthy diets on cardiovascular diseases and all-cause mortality.Methods This study included the individuals aged 35-70 years from 45 cities and 70 rural communities across 12 provinces in China,as part of the Prospective Urban Rural Epidemiology(PURE)study.Dietary habits were assessed using a food frequency questionnaire.The dietary health status was scored using the Alternative Healthy Eating Index(AHEI),with participants in the lowest tertile of AHEI being categorized into the unhealthy diet group,while others were classified as the healthy diet group.The primary endpoints included major cardiovas-cular diseases(myocardial infarction,stroke,or heart failure)and all-cause mortality.Cox proportional hazard models were used to estimate hazard ratios(HR)for each group.Results A total of 40 925 participants were in-cluded in the study,with a median follow-up time of 11.9 years(interquartile range 9.6-12.6 years).During this period,2 066 deaths and 3 099 cases of major cardiovascular diseases were reported.The results showed that un-healthy diet increased the risk of major cardiovascular diseases by 10%(HR=1.10,95%CI:1.02-1.20,P＜0.05)and all-cause mortality by 7%(HR=1.07,95%CI:1.00-1.18,P＜0.05).Among male residents,un-healthy diet did not increase the risk of major cardiovascular diseases or all-cause mortality.However,among female residents,those with an unhealthy diet had a higher risk of major cardiovascular diseases(HR=1.12,95%CI:1.00-1.25,P＜0.05)and all-cause mortality(HR=1.26,95%CI:1.08-1.46,P＜0.05)compared to those with a healthy diet.Conclusions Unhealthy diet increases the risk of major cardiovascular diseases and all-cause mortality,particularly among women.There is a need to raise awareness about healthy dietary to prevent death and the occurrence of major cardiovascular diseases.

Objective To observe the value of preoperative magnetization transfer imaging(MTI)for predicting postoperative pancreatic fistula(POPF)after distal pancreatectomy(DP).Methods A total of 65 patients with pancreatic tumor who underwent DP and preoperative MR scanning were retrospectively enrolled and divided into clinically relevant POPF(CR-POPF)group(n=14,with grade B or C fistula),biochemical fistula group(n=31,postoperative drain fluid amylase level exceeding 3 times the upper limit of normal)and non-fistula group(n=20,postoperative drain fluid amylase level not exceeding 3 times the upper limit of normal)based on postoperative records.Clinical data and magnetization transfer ratio(MTR)of pancreatic tissue at the surgical margin were compared among 3 groups.The predictive value of MTR for CR-POPF was evaluated according to the area under the curve(AUC)of receiver operating characteristic(ROC)curve.Results Patients' age,intraoperative blood loss and the proportion of pancreatic ductal adenocarcinoma in both CR-POPF group and biochemical fistula group were lower than those in non-fistula group(all adjusted P＜0.05),while no significant difference was found between the former two groups(all adjusted P＞0.05).MTR of pancreatic tissue at the surgical margin in CR-POPF group was lower than that in both biochemical fistula group and non-fistula group(both P＜0.05),whereas no statistical difference was detected between the latter two groups(P＞0.05).The AUC of MTR for predicting CR-POPF after DP was 0.727.Conclusion Preoperative MTI could be used to predict POPF after DP.

Acute leukemias caused by mixed lineage leukemia(MLL)gene rearrangements(MLL-r)are characterized by high invasiveness and a poor prognosis,with few specific treatment options available.MLL protein is essential in embryonic development and hematopoiesis.It exhibits histone methyltransferase activity and can interact with various proteins through its functional domains,thus regulating downstream target gene expression through epigenetic modifications.MLL-r leads to the formation of MLL fusion proteins(MLL-FPs),in which the C-terminal is replaced by fusion partner proteins;over 100 such partner proteins have been identified to date.In numerous studies of the molecular mechanism,Menin serves as an important cofacter in the leukemogenesis of MLL-FPs and participates in forming the key complex when interacting with the N terminal of MLL protein,resulting in the disregulation of certain targeted genes,which makes the development of Menin-MLL inhibitors theoretically possible.To date,several small molecules have been identified that inhibit Menin-MLL interaction,including thienopyrimidine derivatives,piperidine derivatives,pyrimidine derivatives,and macrocyclic mimic peptides.Based on these prototypes,at least seven drugs are currently undergoing clinical evaluation,with some promising preliminary data regarding safety,tolerability,and efficacy.This review summarizes the structure and function of MLL,the mechanism of the occurrence of MLL-r leukemia,and current Menin-MLL inhibitors tested in MLL-r leukemia.