Objective There is a large population of patients classified as complex higher-risk and indicated patients(CHIPs)in China with a poor prognosis.The treatment of these patients is complex and challenging,especially whe...Objective There is a large population of patients classified as complex higher-risk and indicated patients(CHIPs)in China with a poor prognosis.The treatment of these patients is complex and challenging,especially when acute cardiac events occur,such as acute coronary syndrome(ACS)or heart failure.Pharmacotherapy and some mechanical circulatory support(MCS)therapeutic devices can provide stable hemodynamic support for CHIPs-percutaneous coronary intervention(PCI).LDL-C is an important pathogenic factor in atherosclerosis,and the target of blood lipid control.Recent studies have revealed that lipoprotein(a)[Lp(a)],which is formed when a covalent bond between apolipoprotein(a)and apolipoprotein B-100 is made,produces an LDL-like particle.This particle is an independent risk factor for the development of atherosclerosis,and is closely correlated to stent thrombosis and restenosis.Furthermore,this requires active intervention.PCSK9 inhibitors have been used in lipid-lowering treatment,and preventing atherosclerosis.The present study explores the efficacy of PCSK9 inhibitors in CHIPs-ACS,and the association between the change in Lp(a)and survival after 2 years of follow-up.Methods The present real-world,prospective control study enrolled 321 CHIPs-ACS who underwent emergency PCI from August 2019 to November 2020,and these patients were followed up for 2 years.These patients were divided into two groups:PCSK9 group(n=161)given the combined PCSK9 inhibitor(140 mg of evolocumab every 2 weeks)and statins-based therapy,and SOC group(n=160)treated with statin-based lipid-lowering therapy alone.Then,the change in lipid index was measured,and the cardiovascular(CV)event recurrence rate was evaluated after one month and 2 years.Afterwards,the contribution of serum lipid parameters,especially the Lp(a)alteration,in patients with earlier initiation of the PCSK9 inhibitor to the CV outcome was analyzed.Results The LDL-C level was significantly reduced in both groups:52.3%in the PCSK9 group and 32.3%(P<0.001)in the SOC group.It is noteworthy that the Lp(a)level decreased by 13.2%in the PCSK9 group,but increased by 30.3%in the SOC group(P<0.001).Furthermore,the number of CV events was not significantly different between the PCSK9 and SOC groups after the 2-year follow-up period.In the PCSK9 group,the Lp(a)reduction was associated with the baseline Lp(a)levels of the patients(r2=−0.315,P<0.001).Moreover,the decrease in Lp(a)contributed to the decline in CV events in patients who received ACS CHIPs-PCI,and the decrease in Lp(a)level was independent of the LDL-C level reduction.Conclusion The early initiation of PCSK9 inhibitors can significantly reduce the LDL-C and Lp(a)levels in ACS CHIPs-PCI.However,further studies are needed to confirm whether PCSK9 inhibitors can reduce the incidence of CV disease in CHIPs.展开更多
The liquid loading is one of the most frequently encountered phenomena in the transportation of gas pipeline,reducing the transmission efficiency and threatening the flow assurance.However,most of the traditional mech...The liquid loading is one of the most frequently encountered phenomena in the transportation of gas pipeline,reducing the transmission efficiency and threatening the flow assurance.However,most of the traditional mechanism models are semi-empirical models,and have to be resolved under different working conditions with complex calculation process.The development of big data technology and artificial intelligence provides the possibility to establish data-driven models.This paper aims to establish a liquid loading prediction model for natural gas pipeline with high generalization ability based on machine learning.First,according to the characteristics of actual gas pipeline,a variety of reasonable combinations of working conditions such as different gas velocity,pipe diameters,water contents and outlet pressures were set,and multiple undulating pipeline topography with different elevation differences was established.Then a large number of simulations were performed by simulator OLGA to obtain the data required for machine learning.After data preprocessing,six supervised learning algorithms,including support vector machine(SVM),decision tree(DT),random forest(RF),artificial neural network(ANN),plain Bayesian classification(NBC),and K nearest neighbor algorithm(KNN),were compared to evaluate the performance of liquid loading prediction.Finally,the RF and KNN with better performance were selected for parameter tuning and then used to the actual pipeline for liquid loading location prediction.Compared with OLGA simulation,the established data-driven model not only improves calculation efficiency and reduces workload,but also can provide technical support for gas pipeline flow assurance.展开更多
Bcl6,a critical pro-oncogene of human B-cell lymphomas,can promote tumor progress.Previous studies have found that Bcl6 participates in hypoxia injury in cardiomyocytes.However,the effect of Bcl6 on cardiac fibroblast...Bcl6,a critical pro-oncogene of human B-cell lymphomas,can promote tumor progress.Previous studies have found that Bcl6 participates in hypoxia injury in cardiomyocytes.However,the effect of Bcl6 on cardiac fibroblasts is still unclear.The aim of this study was to elucidate the functional role of Bcl6 in cardiac fibroblast activation and function.The neonatal rat cardiac fibroblasts were isolated and cultured.First,transforming growth factor β1 (TGFβ1) was used to stimulate fibroblast activation.A decreased expression level of Bcl6 was observed in fibroblasts after stimulation with TGFβ1.Then,cells were transfected with adenovirus Bcl6 to overexpress Bcl6.The results showed that Bcl6 overexpression induced decreased proliferation and reduced activation of fibroblasts which were stimulated with TGFβ1.It was found that activated smad2 and smad3 were not changed by overexpressing Bcl6,but smad4 was decreased.Furthermore,co-immunoprecipitation results showed that Bcl6 directly bound to smad4,and induced down-regulation of smad4.At last,smad4 activator could counteract the anti-fibroblast effects of Bcl6.In conclusion,Bcl6 may negatively regulate cardiac fibroblast activation and function by directly binding to smad4.展开更多
Objective:The nuclear factor erythroid 2(NFE2)-related factor 2(Nrf2)is associated with doxorubicin(DOX)-induced cardiac injury.It has been reported that microRNA-24-3p(miR-24-3p)may regulate the Keapl by mRNA degrada...Objective:The nuclear factor erythroid 2(NFE2)-related factor 2(Nrf2)is associated with doxorubicin(DOX)-induced cardiac injury.It has been reported that microRNA-24-3p(miR-24-3p)may regulate the Keapl by mRNA degradation,whereas Keapl can suppress the activation of Nrf2.However,the role of miR-24-3p in DOX-related cardiotoxicity remains unclear.展开更多
The reliability of a substrate curvature-based stress measurement method for CrN thin films on substrate with fluctuant surface was discussed.The stress error led by the ignorance of substrate thermal deformation was ...The reliability of a substrate curvature-based stress measurement method for CrN thin films on substrate with fluctuant surface was discussed.The stress error led by the ignorance of substrate thermal deformation was studied.Results showed that this error could be as large as several hundred MPa under general deposition conditions.Stress in the CrN thin films with different thicknesses ranging from 110 to 330 nm on stainless steel was studied by this method,in comparison with conventional results on silicon wafer.The thin films＇ morphology and structure were investigated and related to the film stress.A significant result of the comparison is that stress evolution in the thin films on steel obviously differs from that on silicon wafer,not only because the two substrates have different coefficients of thermal expansion,which provokes thermal stress,but also the considerable discrepancy in the thin films＇ grain coarsening rate and structure that induce different intrinsic stresses.展开更多
基金the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University(No.ZNLH-201907)the Hubei Province Health and Family Planning Scientific Research Project(No.WJ2019Q041)the Chinese Academy of Medical Science Innovation Fund for Medical Sciences(No.2021-I2M-1-009).
文摘Objective There is a large population of patients classified as complex higher-risk and indicated patients(CHIPs)in China with a poor prognosis.The treatment of these patients is complex and challenging,especially when acute cardiac events occur,such as acute coronary syndrome(ACS)or heart failure.Pharmacotherapy and some mechanical circulatory support(MCS)therapeutic devices can provide stable hemodynamic support for CHIPs-percutaneous coronary intervention(PCI).LDL-C is an important pathogenic factor in atherosclerosis,and the target of blood lipid control.Recent studies have revealed that lipoprotein(a)[Lp(a)],which is formed when a covalent bond between apolipoprotein(a)and apolipoprotein B-100 is made,produces an LDL-like particle.This particle is an independent risk factor for the development of atherosclerosis,and is closely correlated to stent thrombosis and restenosis.Furthermore,this requires active intervention.PCSK9 inhibitors have been used in lipid-lowering treatment,and preventing atherosclerosis.The present study explores the efficacy of PCSK9 inhibitors in CHIPs-ACS,and the association between the change in Lp(a)and survival after 2 years of follow-up.Methods The present real-world,prospective control study enrolled 321 CHIPs-ACS who underwent emergency PCI from August 2019 to November 2020,and these patients were followed up for 2 years.These patients were divided into two groups:PCSK9 group(n=161)given the combined PCSK9 inhibitor(140 mg of evolocumab every 2 weeks)and statins-based therapy,and SOC group(n=160)treated with statin-based lipid-lowering therapy alone.Then,the change in lipid index was measured,and the cardiovascular(CV)event recurrence rate was evaluated after one month and 2 years.Afterwards,the contribution of serum lipid parameters,especially the Lp(a)alteration,in patients with earlier initiation of the PCSK9 inhibitor to the CV outcome was analyzed.Results The LDL-C level was significantly reduced in both groups:52.3%in the PCSK9 group and 32.3%(P<0.001)in the SOC group.It is noteworthy that the Lp(a)level decreased by 13.2%in the PCSK9 group,but increased by 30.3%in the SOC group(P<0.001).Furthermore,the number of CV events was not significantly different between the PCSK9 and SOC groups after the 2-year follow-up period.In the PCSK9 group,the Lp(a)reduction was associated with the baseline Lp(a)levels of the patients(r2=−0.315,P<0.001).Moreover,the decrease in Lp(a)contributed to the decline in CV events in patients who received ACS CHIPs-PCI,and the decrease in Lp(a)level was independent of the LDL-C level reduction.Conclusion The early initiation of PCSK9 inhibitors can significantly reduce the LDL-C and Lp(a)levels in ACS CHIPs-PCI.However,further studies are needed to confirm whether PCSK9 inhibitors can reduce the incidence of CV disease in CHIPs.
基金supported by the National Science and Technology Major Project of China(2016ZX05066005-001)Zhejiang Province Key Research and Development Plan(2021C03152)Zhoushan Science and Technology Project(2021C21011)
文摘The liquid loading is one of the most frequently encountered phenomena in the transportation of gas pipeline,reducing the transmission efficiency and threatening the flow assurance.However,most of the traditional mechanism models are semi-empirical models,and have to be resolved under different working conditions with complex calculation process.The development of big data technology and artificial intelligence provides the possibility to establish data-driven models.This paper aims to establish a liquid loading prediction model for natural gas pipeline with high generalization ability based on machine learning.First,according to the characteristics of actual gas pipeline,a variety of reasonable combinations of working conditions such as different gas velocity,pipe diameters,water contents and outlet pressures were set,and multiple undulating pipeline topography with different elevation differences was established.Then a large number of simulations were performed by simulator OLGA to obtain the data required for machine learning.After data preprocessing,six supervised learning algorithms,including support vector machine(SVM),decision tree(DT),random forest(RF),artificial neural network(ANN),plain Bayesian classification(NBC),and K nearest neighbor algorithm(KNN),were compared to evaluate the performance of liquid loading prediction.Finally,the RF and KNN with better performance were selected for parameter tuning and then used to the actual pipeline for liquid loading location prediction.Compared with OLGA simulation,the established data-driven model not only improves calculation efficiency and reduces workload,but also can provide technical support for gas pipeline flow assurance.
文摘Bcl6,a critical pro-oncogene of human B-cell lymphomas,can promote tumor progress.Previous studies have found that Bcl6 participates in hypoxia injury in cardiomyocytes.However,the effect of Bcl6 on cardiac fibroblasts is still unclear.The aim of this study was to elucidate the functional role of Bcl6 in cardiac fibroblast activation and function.The neonatal rat cardiac fibroblasts were isolated and cultured.First,transforming growth factor β1 (TGFβ1) was used to stimulate fibroblast activation.A decreased expression level of Bcl6 was observed in fibroblasts after stimulation with TGFβ1.Then,cells were transfected with adenovirus Bcl6 to overexpress Bcl6.The results showed that Bcl6 overexpression induced decreased proliferation and reduced activation of fibroblasts which were stimulated with TGFβ1.It was found that activated smad2 and smad3 were not changed by overexpressing Bcl6,but smad4 was decreased.Furthermore,co-immunoprecipitation results showed that Bcl6 directly bound to smad4,and induced down-regulation of smad4.At last,smad4 activator could counteract the anti-fibroblast effects of Bcl6.In conclusion,Bcl6 may negatively regulate cardiac fibroblast activation and function by directly binding to smad4.
基金This project was supported by National Natural Science Foundation of China(No.80700289)and Medical Research Foundation of Wuhan Municipal Health Commission(No.WX19Q15).
文摘Objective:The nuclear factor erythroid 2(NFE2)-related factor 2(Nrf2)is associated with doxorubicin(DOX)-induced cardiac injury.It has been reported that microRNA-24-3p(miR-24-3p)may regulate the Keapl by mRNA degradation,whereas Keapl can suppress the activation of Nrf2.However,the role of miR-24-3p in DOX-related cardiotoxicity remains unclear.
文摘The reliability of a substrate curvature-based stress measurement method for CrN thin films on substrate with fluctuant surface was discussed.The stress error led by the ignorance of substrate thermal deformation was studied.Results showed that this error could be as large as several hundred MPa under general deposition conditions.Stress in the CrN thin films with different thicknesses ranging from 110 to 330 nm on stainless steel was studied by this method,in comparison with conventional results on silicon wafer.The thin films＇ morphology and structure were investigated and related to the film stress.A significant result of the comparison is that stress evolution in the thin films on steel obviously differs from that on silicon wafer,not only because the two substrates have different coefficients of thermal expansion,which provokes thermal stress,but also the considerable discrepancy in the thin films＇ grain coarsening rate and structure that induce different intrinsic stresses.
