Against the backdrop of the Russia-Ukraine Conflict in 2022,this article reviews the characteristics of traumatic hemorrhage in modern warfare spanning the past century.It investigates several types of tourniquets use...Against the backdrop of the Russia-Ukraine Conflict in 2022,this article reviews the characteristics of traumatic hemorrhage in modern warfare spanning the past century.It investigates several types of tourniquets used by the Russian and Ukrainian armed forces,including limb tourniquets and junctional tourniquets recommended by the Committee on Tactical Combat Casualty Care,tourniquets employed by the Armed Forces of the Russian Federation,and those used by the Armed Forces of Ukraine in the Russia-Ukraine Conflict.The analysis is conducted from perspectives,including the structure,usage methods,and limitations of different tourniquets.Additionally,the article synthesizes the research progress on tourniquets from 3 angles:battlefield adaptability,the impact of tourniquet application methods on patient outcomes,and training in tourniquet usage,offering insights from our team's perspective.展开更多
To the Editor:Atherosclerosis is the main pathological feature of ischemic stroke,which remains a major cause of disability and death worldwide.[1]Vulnerable plaque,was characterized by ulceration,platelet activation,...To the Editor:Atherosclerosis is the main pathological feature of ischemic stroke,which remains a major cause of disability and death worldwide.[1]Vulnerable plaque,was characterized by ulceration,platelet activation,and thrombosis,potentially leading to emboli detachment and stroke.[2]Vascular smooth muscle cells(VSMCs),a major cellular component within lesions,can display pleiotropic phenotypes,including osteogenic or inammatory phenotypes,which may be harmful in maintaining advanced atherosclerotic plaque stability.[3]The modulation of the function of VSMCs,including proliferation,migration,and synthesizing the extracellular matrix(ECM)and matrix metalloproteinase(MMP),is thought to markedly affect plaque formation and vulnerability.[4]Therefore,it is of considerable signicance to drive harmful VSMCs toward VSMCs having benecial properties to strengthen plaque stability and retard plaque development.展开更多
Objective:This study explores the role of methoxy polyethylene glycol@Elabela-11(mPEG@ELA-11),a pHresponsive ELA-11 conjugate,in modulating macrophage function and attenuating atherosclerosis,focusing on the protein k...Objective:This study explores the role of methoxy polyethylene glycol@Elabela-11(mPEG@ELA-11),a pHresponsive ELA-11 conjugate,in modulating macrophage function and attenuating atherosclerosis,focusing on the protein kinase B(AKT)-mediated endoplasmic reticulum(ER)stress pathway as a molecular target.Impact Statement:We reveal that ELA-11 alleviates atherosclerosis by suppressing macrophage foam cell formation,M1 polarization,and apoptosis via the AKT-ER stress pathway.We also develop mPEG@ELA-11,a novel pH-responsive nanocarrier,to enhance targeted drug delivery and therapeutic efficacy,offering a breakthrough for peptide-based cardiovascular nanomedicine.Introduction:Atherosclerosis,driven by macrophage dysfunction and lipid accumulation,is a major global killer.ELA-11,a fragment of Elabela peptide,shows cardiovascular protective effects,but its role in atherosclerosis and optimal delivery remain unstudied.Methods:Elabela mRNA(APELA)expression was analyzed in human carotid atherosclerotic plaques using real-time quantitative PCR analysis,and serum ELA levels were quantified via enzyme-linked immunosorbent assay in patients with carotid stenosis.In vitro studies on RAW264.7 macrophages evaluated mPEG@ELA-11 effects on oxidized low-density lipoprotein-induced foam cell formation,polarization,and apoptosis.In vivo efficacy was tested in ApoE-/-mice,comparing mPEG@ELA-11 with free ELA-11,and its pH-responsive release mechanism was characterized.Results:APELA was downregulated in human atherosclerotic plaques,especially unstable lesions.mPEG@ELA-11 suppressed foam cell formation,M1 polarization,and apoptosis by inhibiting the AKT-ER stress pathway in vitro.In mice,it reduced plaque area more effectively than free ELA-11 attributed to pH-triggered release.Conclusion:The pH-responsive mPEG@ELA-11 alleviates atherosclerosis by modulating macrophages via the AKT-ER stress pathway,with favorable targeting and safety,representing a promising targeted peptide nanomedicine for atherosclerosis.展开更多
文摘Against the backdrop of the Russia-Ukraine Conflict in 2022,this article reviews the characteristics of traumatic hemorrhage in modern warfare spanning the past century.It investigates several types of tourniquets used by the Russian and Ukrainian armed forces,including limb tourniquets and junctional tourniquets recommended by the Committee on Tactical Combat Casualty Care,tourniquets employed by the Armed Forces of the Russian Federation,and those used by the Armed Forces of Ukraine in the Russia-Ukraine Conflict.The analysis is conducted from perspectives,including the structure,usage methods,and limitations of different tourniquets.Additionally,the article synthesizes the research progress on tourniquets from 3 angles:battlefield adaptability,the impact of tourniquet application methods on patient outcomes,and training in tourniquet usage,offering insights from our team's perspective.
基金Specifically Invited Professor of Oriental Scholar of Shanghai Colleges and Universities Tracking Program(No.GZ2016008)National Natural Science Foundation of China(No.81870347)
文摘To the Editor:Atherosclerosis is the main pathological feature of ischemic stroke,which remains a major cause of disability and death worldwide.[1]Vulnerable plaque,was characterized by ulceration,platelet activation,and thrombosis,potentially leading to emboli detachment and stroke.[2]Vascular smooth muscle cells(VSMCs),a major cellular component within lesions,can display pleiotropic phenotypes,including osteogenic or inammatory phenotypes,which may be harmful in maintaining advanced atherosclerotic plaque stability.[3]The modulation of the function of VSMCs,including proliferation,migration,and synthesizing the extracellular matrix(ECM)and matrix metalloproteinase(MMP),is thought to markedly affect plaque formation and vulnerability.[4]Therefore,it is of considerable signicance to drive harmful VSMCs toward VSMCs having benecial properties to strengthen plaque stability and retard plaque development.
基金supported by the National Natural Science Foundation of China(82270481,82470481,and 82370498)the Shuang Bai Ren Project of Shanghai Jiao Tong University(JYYJXYS20240821)the Medical Scientific Research Project of Shanghai Hongkou Health Commission(Hongwei 2302-17 and 2302-22).
文摘Objective:This study explores the role of methoxy polyethylene glycol@Elabela-11(mPEG@ELA-11),a pHresponsive ELA-11 conjugate,in modulating macrophage function and attenuating atherosclerosis,focusing on the protein kinase B(AKT)-mediated endoplasmic reticulum(ER)stress pathway as a molecular target.Impact Statement:We reveal that ELA-11 alleviates atherosclerosis by suppressing macrophage foam cell formation,M1 polarization,and apoptosis via the AKT-ER stress pathway.We also develop mPEG@ELA-11,a novel pH-responsive nanocarrier,to enhance targeted drug delivery and therapeutic efficacy,offering a breakthrough for peptide-based cardiovascular nanomedicine.Introduction:Atherosclerosis,driven by macrophage dysfunction and lipid accumulation,is a major global killer.ELA-11,a fragment of Elabela peptide,shows cardiovascular protective effects,but its role in atherosclerosis and optimal delivery remain unstudied.Methods:Elabela mRNA(APELA)expression was analyzed in human carotid atherosclerotic plaques using real-time quantitative PCR analysis,and serum ELA levels were quantified via enzyme-linked immunosorbent assay in patients with carotid stenosis.In vitro studies on RAW264.7 macrophages evaluated mPEG@ELA-11 effects on oxidized low-density lipoprotein-induced foam cell formation,polarization,and apoptosis.In vivo efficacy was tested in ApoE-/-mice,comparing mPEG@ELA-11 with free ELA-11,and its pH-responsive release mechanism was characterized.Results:APELA was downregulated in human atherosclerotic plaques,especially unstable lesions.mPEG@ELA-11 suppressed foam cell formation,M1 polarization,and apoptosis by inhibiting the AKT-ER stress pathway in vitro.In mice,it reduced plaque area more effectively than free ELA-11 attributed to pH-triggered release.Conclusion:The pH-responsive mPEG@ELA-11 alleviates atherosclerosis by modulating macrophages via the AKT-ER stress pathway,with favorable targeting and safety,representing a promising targeted peptide nanomedicine for atherosclerosis.
