As the search for effective treatments for COVID-19 continues,the high mortality rate among critically ill patients in Intensive Care Units(ICU)presents a profound challenge.This study explores the potential benefits ...As the search for effective treatments for COVID-19 continues,the high mortality rate among critically ill patients in Intensive Care Units(ICU)presents a profound challenge.This study explores the potential benefits of traditional Chinese medicine(TCM)as a supplementary treatment for severe COVID-19.A total of 110 critically ill COVID-19 patients at the Intensive Care Unit(ICU)of Vulcan Hill Hospital between Feb.,2020,and April,2020(Wuhan,China)participated in this observational study.All patients received standard supportive care protocols,with a subset of 81 also receiving TCM as an adjunct treatment.Clinical characteristics during the treatment period and the clinical outcome of each patient were closely monitored and analysed.Our findings indicated that the TCM group exhibited a significantly lower mortality rate compared with the non-TCM group(16 of 81 vs 24 of 29;0.3 vs 2.3 person/month).In the adjusted Cox proportional hazards models,TCM treatment was associated with improved survival odds(P<0.001).Furthermore,the analysis also revealed that TCM treatment could partially mitigate inflammatory responses,as evidenced by the reduced levels of proinflammatory cytokines,and contribute to the recovery of multiple organic functions,thereby potentially increasing the survival rate of critically ill COVID-19 patients.展开更多
Gene therapy employs exogenous nucleic acids to treat genetic diseases and disorders.The insufficient cytosolic delivery of genetic materials remains a major hurdle for effective gene therapy.To address this challenge...Gene therapy employs exogenous nucleic acids to treat genetic diseases and disorders.The insufficient cytosolic delivery of genetic materials remains a major hurdle for effective gene therapy.To address this challenge,we have designed and synthesized various cationic protein nanocapsules that can efficiently condense nucleic acids via self-assembly.Through systematically investigating the gene transfection efficiency of these nanocapsules as delivery vectors,we find that nanocapsules,which were synthesized with hydrolyzable polymers containing tertiary amine groups,afford the highest transfection efficiency(〜80%),resulting in stable protein expression for over four days.The mechanistic study reveals that tertiary amine groups facilitate the endosomal escape of the nucleic acid-nanocapsule complexes after their cell internalization via endocytosis.The subsequent hydrolysis of the polymers triggers the cytosolic release of the nucleic acids,thereby prompting gene expression.Our results not only provide a new class of gene delivery vectors but also detail the parameters for future vector design.展开更多
基金This work was supported by the National Science Foundation for Young Scientists of China(No.82100096)the National Science Foundation for Young Scientists of Beijing(No.7214254)+1 种基金the National Natural Science Foundation of China(Nos.81902426 and 81872441)the Emergency Scientific Research Project for COVID-19(No.20yjky007).
文摘As the search for effective treatments for COVID-19 continues,the high mortality rate among critically ill patients in Intensive Care Units(ICU)presents a profound challenge.This study explores the potential benefits of traditional Chinese medicine(TCM)as a supplementary treatment for severe COVID-19.A total of 110 critically ill COVID-19 patients at the Intensive Care Unit(ICU)of Vulcan Hill Hospital between Feb.,2020,and April,2020(Wuhan,China)participated in this observational study.All patients received standard supportive care protocols,with a subset of 81 also receiving TCM as an adjunct treatment.Clinical characteristics during the treatment period and the clinical outcome of each patient were closely monitored and analysed.Our findings indicated that the TCM group exhibited a significantly lower mortality rate compared with the non-TCM group(16 of 81 vs 24 of 29;0.3 vs 2.3 person/month).In the adjusted Cox proportional hazards models,TCM treatment was associated with improved survival odds(P<0.001).Furthermore,the analysis also revealed that TCM treatment could partially mitigate inflammatory responses,as evidenced by the reduced levels of proinflammatory cytokines,and contribute to the recovery of multiple organic functions,thereby potentially increasing the survival rate of critically ill COVID-19 patients.
基金supported by the National Science and Technology Major Project(Nos.2018ZX09J18101 and 2019ZX09J19103)the National Natural Science Foundation of China(No.81703048).
文摘Gene therapy employs exogenous nucleic acids to treat genetic diseases and disorders.The insufficient cytosolic delivery of genetic materials remains a major hurdle for effective gene therapy.To address this challenge,we have designed and synthesized various cationic protein nanocapsules that can efficiently condense nucleic acids via self-assembly.Through systematically investigating the gene transfection efficiency of these nanocapsules as delivery vectors,we find that nanocapsules,which were synthesized with hydrolyzable polymers containing tertiary amine groups,afford the highest transfection efficiency(〜80%),resulting in stable protein expression for over four days.The mechanistic study reveals that tertiary amine groups facilitate the endosomal escape of the nucleic acid-nanocapsule complexes after their cell internalization via endocytosis.The subsequent hydrolysis of the polymers triggers the cytosolic release of the nucleic acids,thereby prompting gene expression.Our results not only provide a new class of gene delivery vectors but also detail the parameters for future vector design.
