Background Cardiac resynchronization therapy （CRT） with biventricular pacing improves cardiac function,functional capacity and quality of life in selected patients with heart failure.The current study aimed to evalu...Background Cardiac resynchronization therapy （CRT） with biventricular pacing improves cardiac function,functional capacity and quality of life in selected patients with heart failure.The current study aimed to evaluate the efficacy of the intracardiac electrogram （IEGM）-based optimization method,QuickOptTM,in Chinese patients treated with CRT.Methods Aortic time velocity integrals （AVTI） achieved at the sensed atrioventricular （AV）,paced AV and interventricular （VV） interval settings recommended by both QuickOptTM and standard echocardiographic optimization were measured in 101 patients.Consistency and the strength of the relationship between the two timing cycle optimization methods were assessed by intra-class correlation coefficient （ICC）.Results The ICC showed good agreement and correlation with what the AVTI achieved at the optimal sensed AV （ICC=0.9683 （0.9535-0.9785））,paced AV （ICC=0.9642 （0.9475-0.9757）） and VV （ICC=0.9730 （0.9602-0.9817）） interval settings determined by the two optimization methods.The average time required by echocardiographic optimization and by QuickOptTM were （78.32±32.40） minutes and （1.98±1.64） minutes respectively （P 〈0.0001）.Conclusion The QuickOptTM algorithm provides a quicker,simpler and reliable alternative to the standard method for timing cycle optimization.（ClinicaITrial.gov Reference Number：NCT00918294）展开更多
It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in thedfferentiated populations with complex diseases,as stable coronary heart disease...It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in thedfferentiated populations with complex diseases,as stable coronary heart disease.Here,in an adaptive,31-center,randomized,double-blind trial invoving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI),a kind of polyphamacological drug with high quality control,or placebo(0.9%saline),with 76-day following-up,we firstly confrmed that DHl couldincrease the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire(ASAQ-AF220)(12.78%at Day 30,95%confidence interval[C]5.86-19.71%,P=0.0003,13.82%at Day 6C0,95%CI 6.82-20.82%,P=0.0001and 8.95%at Day 90,95%CI 2.06-15.85%,P=0.01).We also found that there were no significant differences in new-onset major vascularevents(P=0.8502)and serious adverse events(P=0.9105)between DHl and placebo.After performing the RNA sequencing in 62 selectedpatients,we developed a systemic modular approach tp identfy differentilly expressed modules(DEMs)of DHI with the Z_(summay)valueless than 0 compared with the control group,calculated by weighted gene co-expression network analysis(WGCNA),and sketched out thebasic framework on a modular map with 25 functional modules targeted by DII.Furthermore,the effective therapeutic module(ETM),defined as the highest corelation value with the phenotype alteration(SAQ-AF,the change in SAQ-AF at Day 30 from baseline)calculatedby WGCNA,was identifed in the population with the best effect(ASAQ-AF240),which is related to anticoagulation and regulation ofcholesterol metabolism.We assessed the modular flexbility of this ETM using the global topological D value based on Euclidean distance,which is corelated with phenotype alteration(r^(2):0.8204,P=0.019)by linear regression.Our study identified the ant-angina therapeuticmodule in the effective population treated by the multi-target drug.Modular methods facilitate the discovery of展开更多
A microstructure composed of martensite matrix,lower bainite,and stable film-like austenite was designed by a quenching and isothermal bainitic holding process in a 0.30C–2.69Mn–1.71Si(wt.%)steel.The yield strength,...A microstructure composed of martensite matrix,lower bainite,and stable film-like austenite was designed by a quenching and isothermal bainitic holding process in a 0.30C–2.69Mn–1.71Si(wt.%)steel.The yield strength,tensile strength,and ductile-to-brittle transition temperature(DBTT)of the high-strength steel thus obtained were 1263 MPa,1521 MPa,and-33℃,respectively,and at-20℃,it showed superior low-temperature toughness,which reached 77.5 J/cm^(2).Meanwhile,it showed excellent hydrogen embrittlement(HE)resistance,and the total elongation loss is only 3.1%after 15 min of hydrogen charging.The excellent comprehensive performance is attributed to the fact that fine stable austenite with film-like morphology hindered the crack nucleation and propagation,and hindered hydrogen diffusion as a hydrogen trap.However,with a decrease in the isothermal temperature,transition carbide precipitation was accompanied by a further decrease in austenite grain size.For this condition,although transition carbides can act as effective hydrogen traps,excessive precipitation decreased the carbon content of retained austenite and increased the deformation heterogeneity between austenite and martensite matrix,leading to weakened austenite stability and HE resistance,a total elongation loss of approximately 39%(15 min hydrogen charging),a sharp decrease in impact toughness,and an increase in DBTT.The competitive role of film-like austenite and transition carbides on the comprehensive mechanical performance of steel is revealed,especially the suppression of crack nucleation and propagation that will provide a guide for the design of high strength steels with excellent impact toughness and HE resistance.展开更多
文摘Background Cardiac resynchronization therapy （CRT） with biventricular pacing improves cardiac function,functional capacity and quality of life in selected patients with heart failure.The current study aimed to evaluate the efficacy of the intracardiac electrogram （IEGM）-based optimization method,QuickOptTM,in Chinese patients treated with CRT.Methods Aortic time velocity integrals （AVTI） achieved at the sensed atrioventricular （AV）,paced AV and interventricular （VV） interval settings recommended by both QuickOptTM and standard echocardiographic optimization were measured in 101 patients.Consistency and the strength of the relationship between the two timing cycle optimization methods were assessed by intra-class correlation coefficient （ICC）.Results The ICC showed good agreement and correlation with what the AVTI achieved at the optimal sensed AV （ICC=0.9683 （0.9535-0.9785））,paced AV （ICC=0.9642 （0.9475-0.9757）） and VV （ICC=0.9730 （0.9602-0.9817）） interval settings determined by the two optimization methods.The average time required by echocardiographic optimization and by QuickOptTM were （78.32±32.40） minutes and （1.98±1.64） minutes respectively （P 〈0.0001）.Conclusion The QuickOptTM algorithm provides a quicker,simpler and reliable alternative to the standard method for timing cycle optimization.（ClinicaITrial.gov Reference Number：NCT00918294）
基金funded by China National Science and Technology Major Project for"Significant New Drugs Development"(2011ZX09304-07)National Natural Science Foundation of China(81673833)China Fundamental Research Funds for the Central Public Welfare Research Institutes(ZZ0908029).
文摘It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in thedfferentiated populations with complex diseases,as stable coronary heart disease.Here,in an adaptive,31-center,randomized,double-blind trial invoving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI),a kind of polyphamacological drug with high quality control,or placebo(0.9%saline),with 76-day following-up,we firstly confrmed that DHl couldincrease the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire(ASAQ-AF220)(12.78%at Day 30,95%confidence interval[C]5.86-19.71%,P=0.0003,13.82%at Day 6C0,95%CI 6.82-20.82%,P=0.0001and 8.95%at Day 90,95%CI 2.06-15.85%,P=0.01).We also found that there were no significant differences in new-onset major vascularevents(P=0.8502)and serious adverse events(P=0.9105)between DHl and placebo.After performing the RNA sequencing in 62 selectedpatients,we developed a systemic modular approach tp identfy differentilly expressed modules(DEMs)of DHI with the Z_(summay)valueless than 0 compared with the control group,calculated by weighted gene co-expression network analysis(WGCNA),and sketched out thebasic framework on a modular map with 25 functional modules targeted by DII.Furthermore,the effective therapeutic module(ETM),defined as the highest corelation value with the phenotype alteration(SAQ-AF,the change in SAQ-AF at Day 30 from baseline)calculatedby WGCNA,was identifed in the population with the best effect(ASAQ-AF240),which is related to anticoagulation and regulation ofcholesterol metabolism.We assessed the modular flexbility of this ETM using the global topological D value based on Euclidean distance,which is corelated with phenotype alteration(r^(2):0.8204,P=0.019)by linear regression.Our study identified the ant-angina therapeuticmodule in the effective population treated by the multi-target drug.Modular methods facilitate the discovery of
基金the National Key R&D Program of China(No.2021YFB3702401)Major Program of the National Natural Science Foundation of China(No.52293394)the National Natural Science Foundation of China(Nos.U1564203,51571141 and 51201105).
文摘A microstructure composed of martensite matrix,lower bainite,and stable film-like austenite was designed by a quenching and isothermal bainitic holding process in a 0.30C–2.69Mn–1.71Si(wt.%)steel.The yield strength,tensile strength,and ductile-to-brittle transition temperature(DBTT)of the high-strength steel thus obtained were 1263 MPa,1521 MPa,and-33℃,respectively,and at-20℃,it showed superior low-temperature toughness,which reached 77.5 J/cm^(2).Meanwhile,it showed excellent hydrogen embrittlement(HE)resistance,and the total elongation loss is only 3.1%after 15 min of hydrogen charging.The excellent comprehensive performance is attributed to the fact that fine stable austenite with film-like morphology hindered the crack nucleation and propagation,and hindered hydrogen diffusion as a hydrogen trap.However,with a decrease in the isothermal temperature,transition carbide precipitation was accompanied by a further decrease in austenite grain size.For this condition,although transition carbides can act as effective hydrogen traps,excessive precipitation decreased the carbon content of retained austenite and increased the deformation heterogeneity between austenite and martensite matrix,leading to weakened austenite stability and HE resistance,a total elongation loss of approximately 39%(15 min hydrogen charging),a sharp decrease in impact toughness,and an increase in DBTT.The competitive role of film-like austenite and transition carbides on the comprehensive mechanical performance of steel is revealed,especially the suppression of crack nucleation and propagation that will provide a guide for the design of high strength steels with excellent impact toughness and HE resistance.
