Intelligent and connected vehicles(ICVs)are confronted with critically complex traffic scenarios and safety challenges that have attracted increasing attention from academia and industry.The intelligent safety of ICVs...Intelligent and connected vehicles(ICVs)are confronted with critically complex traffic scenarios and safety challenges that have attracted increasing attention from academia and industry.The intelligent safety of ICVs involves several technologies and requires the common efforts of researchers and engineers,including the safety of the intended functionality(SOTIF),the safety of artificial intelligence,the intricacies of cybersecurity,and ethical dilemmas.Ensuring the intelligent safety of ICVs presents substantial chal-lenges in both research and commercialization,particularly SOTIF,which refers to the absence of unreasonable risk owing to hazards resulting from functional insufficiencies of the intended functiona-lity or reasonably foreseeable misuse by person.Because of the limited scene coverage ability of training samples and the practical application conditions without boundary restrictions,it is very dif-ficult to find the functional insufficiency of the intended function-ality and overcome it under dynamic unknown scenarios,which is also the source of SOTIF.展开更多
Epinephrine is often used for the treatment of patients with heart failure, low cardiac output and cardiac arrest. It can acutely improve hemodynamic parameters; however, it does not seem to improve longer term clinic...Epinephrine is often used for the treatment of patients with heart failure, low cardiac output and cardiac arrest. It can acutely improve hemodynamic parameters; however, it does not seem to improve longer term clinical outcomes. Therefore, we hypothesized that epinephrine may induce unfavorable changes in gene expression of cardiomyocyte. Thus, we investigated effects of epinephrine exposure on the mediation or modulation of gene expression of cultured cardiomyocytes at a genome-wide scale. Our investigation revealed that exposure of cardiomyocytes to epinephrine in an in vitro environment can up-regulate the expression ofangiopoietin-2 gene （~ 2.1 times）, and down-regulate the gene expression of neuregulin 1 （-3.7 times）, plasminogen activator inhibitor-1 （-2.4 times） and SPARC-related modular calcium-binding protein-2 （-4.5 times）. These changes suggest that epinephrine exposure may induce inhibition of angiogenesis-related gene expressions in cultured rat cardiomyocytes. The precise clinical significance of these changes in gene expression, which was induced by epinephrine exposure, warrants further experimental and clinical investigations.展开更多
Congestive heart failure(CHF)is defined as a cardiac dysfunction leading to low cardiac output and inadequate tissue perfusion.Intravenous positive inotropes are used to increase myocardial contractility in hospitaliz...Congestive heart failure(CHF)is defined as a cardiac dysfunction leading to low cardiac output and inadequate tissue perfusion.Intravenous positive inotropes are used to increase myocardial contractility in hospitalized patients with advanced heart failure.Milrinone is a phosphodiesterase Ⅲ inhibitor and used most commonly for inotropic effect.The well-known PROMISE study investigated the effects of milrinone on mortality in patients with severe CHF,and concluded that long-term therapy with milrinone increased morbidity and mortality armong patients with advanced CHF.Previous studies have suggested that phosphodiesterase inhibitors can have potential effects on inflammatory pathways.Hence,we hypothesized that milrinone may alter inflammatory gene expressions in cardiomyocytes,thus leading to adverse clinical outcomes.We used rat cardiomyocyte cell line H9 C2 and studied the impact of exposing cardiomyocytes to milrinone(10 μmol/L)for 24 hours on inflammatory gene expressions.RNA extracted from cultured cardiomyocytes was used for whole rat genome gene expression assay(41 000 genes).The following changes in inflammatory response-related gene expressions were discovered.Genes with increased expressions included:THBS2(+ 9.98),MMP2(+3.47),DDIT3(+2.39),and ADORA3(+3.5).Genes with decreased expressions were:SPP1(-5.28)and CD14(-2.05).We found that the above mentioned gene expression changes seem to indicate that milrinone may hinder the inflammatory process which may potentially lead to adverse clinical outcomes.However,further in vivo and clinical investigations will be needed to illustrate the clinical relevance of these gene expression changes induced by milrinone.展开更多
文摘Intelligent and connected vehicles(ICVs)are confronted with critically complex traffic scenarios and safety challenges that have attracted increasing attention from academia and industry.The intelligent safety of ICVs involves several technologies and requires the common efforts of researchers and engineers,including the safety of the intended functionality(SOTIF),the safety of artificial intelligence,the intricacies of cybersecurity,and ethical dilemmas.Ensuring the intelligent safety of ICVs presents substantial chal-lenges in both research and commercialization,particularly SOTIF,which refers to the absence of unreasonable risk owing to hazards resulting from functional insufficiencies of the intended functiona-lity or reasonably foreseeable misuse by person.Because of the limited scene coverage ability of training samples and the practical application conditions without boundary restrictions,it is very dif-ficult to find the functional insufficiency of the intended function-ality and overcome it under dynamic unknown scenarios,which is also the source of SOTIF.
基金supported by internal funding from the Department of Anesthesiology and Perioperative Medicine
文摘Epinephrine is often used for the treatment of patients with heart failure, low cardiac output and cardiac arrest. It can acutely improve hemodynamic parameters; however, it does not seem to improve longer term clinical outcomes. Therefore, we hypothesized that epinephrine may induce unfavorable changes in gene expression of cardiomyocyte. Thus, we investigated effects of epinephrine exposure on the mediation or modulation of gene expression of cultured cardiomyocytes at a genome-wide scale. Our investigation revealed that exposure of cardiomyocytes to epinephrine in an in vitro environment can up-regulate the expression ofangiopoietin-2 gene （~ 2.1 times）, and down-regulate the gene expression of neuregulin 1 （-3.7 times）, plasminogen activator inhibitor-1 （-2.4 times） and SPARC-related modular calcium-binding protein-2 （-4.5 times）. These changes suggest that epinephrine exposure may induce inhibition of angiogenesis-related gene expressions in cultured rat cardiomyocytes. The precise clinical significance of these changes in gene expression, which was induced by epinephrine exposure, warrants further experimental and clinical investigations.
基金fully supported by an intemal funding from the Department of Anesthesiology&Perioperative Medicine to Dr. Henry Liu
文摘Congestive heart failure(CHF)is defined as a cardiac dysfunction leading to low cardiac output and inadequate tissue perfusion.Intravenous positive inotropes are used to increase myocardial contractility in hospitalized patients with advanced heart failure.Milrinone is a phosphodiesterase Ⅲ inhibitor and used most commonly for inotropic effect.The well-known PROMISE study investigated the effects of milrinone on mortality in patients with severe CHF,and concluded that long-term therapy with milrinone increased morbidity and mortality armong patients with advanced CHF.Previous studies have suggested that phosphodiesterase inhibitors can have potential effects on inflammatory pathways.Hence,we hypothesized that milrinone may alter inflammatory gene expressions in cardiomyocytes,thus leading to adverse clinical outcomes.We used rat cardiomyocyte cell line H9 C2 and studied the impact of exposing cardiomyocytes to milrinone(10 μmol/L)for 24 hours on inflammatory gene expressions.RNA extracted from cultured cardiomyocytes was used for whole rat genome gene expression assay(41 000 genes).The following changes in inflammatory response-related gene expressions were discovered.Genes with increased expressions included:THBS2(+ 9.98),MMP2(+3.47),DDIT3(+2.39),and ADORA3(+3.5).Genes with decreased expressions were:SPP1(-5.28)and CD14(-2.05).We found that the above mentioned gene expression changes seem to indicate that milrinone may hinder the inflammatory process which may potentially lead to adverse clinical outcomes.However,further in vivo and clinical investigations will be needed to illustrate the clinical relevance of these gene expression changes induced by milrinone.
