目的探究沙库巴曲缬沙坦联合琥珀酸美托洛尔缓释片治疗冠状动脉粥样硬化性心脏病(以下简称冠心病)并慢性心力衰竭患者的效果。方法选取于2017年9月至2018年9月在河南科技大学第三附属医院和郑州市心血管病医院住院的冠心病并慢性心力衰...目的探究沙库巴曲缬沙坦联合琥珀酸美托洛尔缓释片治疗冠状动脉粥样硬化性心脏病(以下简称冠心病)并慢性心力衰竭患者的效果。方法选取于2017年9月至2018年9月在河南科技大学第三附属医院和郑州市心血管病医院住院的冠心病并慢性心力衰竭患者为研究对象,按照入院顺序及年龄、病程、性别组间均衡的原则分为观察组(n=94)与对照组(n=93)。观察组给予沙库巴曲缬沙坦联合琥珀酸美托洛尔缓释片治疗,对照组给予琥珀酸美托洛尔缓释片治疗。两组患者均连续治疗6个月,对比两组治疗效果及治疗前后心功能指标:舒张早期最大充盈速度(maximum early filling speed,E)、左心室射血分数(ejection fraction,EF)、舒张晚期最大充盈速度(maximum filling speed in late diastole,A)、E/A、血管内皮功能[血浆内皮素(endothelin,ET)、降钙素基因相关肽(calcitonin gene-related peptide,CGRP)、一氧化氮(nitric oxide,NO)]。结果观察组临床治疗效果(93.62%)高于对照组(78.49%),差异有统计学意义(P<0.05);治疗后观察组的E、EF、E/A、CGRP、NO高于对照组,A、ET低于对照组,差异均有统计学意义(P<0.05)。结论沙库巴曲缬沙坦联合琥珀酸美托洛尔缓释片治疗冠心病并慢性心力衰竭患者治疗效果显著,可有效改善冠心病并慢性心力衰竭患者心功能。展开更多
African swine fever(ASF)is a devastating infectious disease in swine that is severely threatening the global pig industry.An efficacious vaccine is urgently required.Here,we used the Chinese ASFV HLJ/18 as a backbone ...African swine fever(ASF)is a devastating infectious disease in swine that is severely threatening the global pig industry.An efficacious vaccine is urgently required.Here,we used the Chinese ASFV HLJ/18 as a backbone and generated a series of genedeleted viruses.The virulence,immunogenicity,safety,and protective efficacy evaluation in specific-pathogen-free pigs,commercial pigs,and pregnant sows indicated that one virus,namely HLJ/18-7GD,which has seven genes deleted,is fully attenuated in pigs,cannot convert to the virulent strain,and provides complete protection of pigs against lethal ASFV challenge.Our study shows that HLJ/-18-7GD is a safe and effective vaccine against ASFV,and as such is expected to play an important role in controlling the spread of ASFV.展开更多
Rheumatoid arthritis（RA） is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. A...Rheumatoid arthritis（RA） is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. A better understanding of how the pathological mechanisms drive the deterioration of RA progress in individuals is urgently required in order to develop therapies that will effectively treat patients at each stage of the disease progress. Here we dissect the etiology and pathology at specific stages：（i） triggering,（ii） maturation,（iii） targeting, and（iv） fulminant stage, concomitant with hyperplastic synovium, cartilage damage, bone erosion, and systemic consequences. Modern pharmacologic therapies（including conventional, biological, and novel potential small molecule disease-modifying anti-rheumatic drugs） remain the mainstay of RA treatment and there has been significant progress toward achieving disease remission without joint deformity. Despite this, a significant proportion of RA patients do not effectively respond to the current therapies and thus new drugs are urgently required. This review discusses recent advances of our understanding of RA pathogenesis, disease modifying drugs, and provides perspectives on next generation therapeutics for RA.展开更多
Wnt signaling transduces evolutionarily conserved pathways which play important roles in initiating and regulating a diverse range of cellular activities,including cell proliferation,calcium homeostasis,and cell polar...Wnt signaling transduces evolutionarily conserved pathways which play important roles in initiating and regulating a diverse range of cellular activities,including cell proliferation,calcium homeostasis,and cell polarity.The role of Wnt signaling in controlling cell proliferation and stem cell self-renewal is primarily carried out through the canonical pathway,which is the best-characterized the multiple Wnt signaling branches.The past 10 years has seen a rapid expansion in our understanding of the complexity of this pathway,as many new components of Wnt signaling have been identified and linked to signaling regulation,stem cell functions,and adult tissue homeostasis.Additionally,a substantial body of evidence links Wnt signaling to tumorigenesis of cancer types and implicates it in the development of cancer drug resistance.Thus,a better understanding of the mechanisms by which dysregulation of Wnt signaling precedes the development and progression of human cancer may hasten the development of pathway inhibitors to augment current therapy.This review summarizes and synthesizes our current knowledge of the canonical Wnt pathway in development and disease.We begin with an overview of the components of the canonical Wnt signaling pathway and delve into the role this pathway has been shown to play in stemness,tumorigenesis,and cancer drug resistance.Ultimately,we hope to present an organized collection of evidence implicating Wnt signaling in tumorigenesis and chemoresistance to facilitate the pursuit of Wnt pathway modulators that may improve outcomes of cancers in which Wnt signaling contributes to aggressive disease and/or treatment resistance.展开更多
文摘目的探究沙库巴曲缬沙坦联合琥珀酸美托洛尔缓释片治疗冠状动脉粥样硬化性心脏病(以下简称冠心病)并慢性心力衰竭患者的效果。方法选取于2017年9月至2018年9月在河南科技大学第三附属医院和郑州市心血管病医院住院的冠心病并慢性心力衰竭患者为研究对象,按照入院顺序及年龄、病程、性别组间均衡的原则分为观察组(n=94)与对照组(n=93)。观察组给予沙库巴曲缬沙坦联合琥珀酸美托洛尔缓释片治疗,对照组给予琥珀酸美托洛尔缓释片治疗。两组患者均连续治疗6个月,对比两组治疗效果及治疗前后心功能指标:舒张早期最大充盈速度(maximum early filling speed,E)、左心室射血分数(ejection fraction,EF)、舒张晚期最大充盈速度(maximum filling speed in late diastole,A)、E/A、血管内皮功能[血浆内皮素(endothelin,ET)、降钙素基因相关肽(calcitonin gene-related peptide,CGRP)、一氧化氮(nitric oxide,NO)]。结果观察组临床治疗效果(93.62%)高于对照组(78.49%),差异有统计学意义(P<0.05);治疗后观察组的E、EF、E/A、CGRP、NO高于对照组,A、ET低于对照组,差异均有统计学意义(P<0.05)。结论沙库巴曲缬沙坦联合琥珀酸美托洛尔缓释片治疗冠心病并慢性心力衰竭患者治疗效果显著,可有效改善冠心病并慢性心力衰竭患者心功能。
基金supported by the National Key R&D Program of China(2018YFC1200601)Applied Technology Research and Development Project of Heilongjiang Province(GA19B301)+1 种基金Key-Area Research and Development Program of Guangdong Province(2019B020211004)the grant from the State Key Laboratory of Veterinary Biotechnology Program(SKLVBP201801)。
文摘African swine fever(ASF)is a devastating infectious disease in swine that is severely threatening the global pig industry.An efficacious vaccine is urgently required.Here,we used the Chinese ASFV HLJ/18 as a backbone and generated a series of genedeleted viruses.The virulence,immunogenicity,safety,and protective efficacy evaluation in specific-pathogen-free pigs,commercial pigs,and pregnant sows indicated that one virus,namely HLJ/18-7GD,which has seven genes deleted,is fully attenuated in pigs,cannot convert to the virulent strain,and provides complete protection of pigs against lethal ASFV challenge.Our study shows that HLJ/-18-7GD is a safe and effective vaccine against ASFV,and as such is expected to play an important role in controlling the spread of ASFV.
基金supported in part by the Australian National Health and Medical Research Council (NHMRC, No. 1107828)Arthritis foundation of Australiathe University of Western Australia Research Collaboration Awards
文摘Rheumatoid arthritis（RA） is a chronic systemic autoimmune disease that primarily affects the lining of the synovial joints and is associated with progressive disability, premature death, and socioeconomic burdens. A better understanding of how the pathological mechanisms drive the deterioration of RA progress in individuals is urgently required in order to develop therapies that will effectively treat patients at each stage of the disease progress. Here we dissect the etiology and pathology at specific stages：（i） triggering,（ii） maturation,（iii） targeting, and（iv） fulminant stage, concomitant with hyperplastic synovium, cartilage damage, bone erosion, and systemic consequences. Modern pharmacologic therapies（including conventional, biological, and novel potential small molecule disease-modifying anti-rheumatic drugs） remain the mainstay of RA treatment and there has been significant progress toward achieving disease remission without joint deformity. Despite this, a significant proportion of RA patients do not effectively respond to the current therapies and thus new drugs are urgently required. This review discusses recent advances of our understanding of RA pathogenesis, disease modifying drugs, and provides perspectives on next generation therapeutics for RA.
基金The authors’research efforts were supported in part by research grants from the NIH(AT004418 to TCH)the 973 Program of Ministry of Science and Technology(MOST)of China(#2011CB707900 to TCH)+1 种基金the Scoliosis Research Society(to MJL),MKM was a recipient of Howard Hughes Medical Institute Medical Research FellowshipCS was a recipient of the Pritzker Summer Research Fellowship funded through a NIH T-35 training grant(NIDDK).
文摘Wnt signaling transduces evolutionarily conserved pathways which play important roles in initiating and regulating a diverse range of cellular activities,including cell proliferation,calcium homeostasis,and cell polarity.The role of Wnt signaling in controlling cell proliferation and stem cell self-renewal is primarily carried out through the canonical pathway,which is the best-characterized the multiple Wnt signaling branches.The past 10 years has seen a rapid expansion in our understanding of the complexity of this pathway,as many new components of Wnt signaling have been identified and linked to signaling regulation,stem cell functions,and adult tissue homeostasis.Additionally,a substantial body of evidence links Wnt signaling to tumorigenesis of cancer types and implicates it in the development of cancer drug resistance.Thus,a better understanding of the mechanisms by which dysregulation of Wnt signaling precedes the development and progression of human cancer may hasten the development of pathway inhibitors to augment current therapy.This review summarizes and synthesizes our current knowledge of the canonical Wnt pathway in development and disease.We begin with an overview of the components of the canonical Wnt signaling pathway and delve into the role this pathway has been shown to play in stemness,tumorigenesis,and cancer drug resistance.Ultimately,we hope to present an organized collection of evidence implicating Wnt signaling in tumorigenesis and chemoresistance to facilitate the pursuit of Wnt pathway modulators that may improve outcomes of cancers in which Wnt signaling contributes to aggressive disease and/or treatment resistance.
