Objective PERK/elF2/CHOP is a major signaling pathway mediating endoplasmic reticulum （ER） stress related with atherosclerosis. Oxidized LDL （ox-LDL） also induces endothelial apoptosis and plays a vital role in th...Objective PERK/elF2/CHOP is a major signaling pathway mediating endoplasmic reticulum （ER） stress related with atherosclerosis. Oxidized LDL （ox-LDL） also induces endothelial apoptosis and plays a vital role in the initiation and progression of atherosclerosis. The present study was conducted to explore the regulatory effect of ox-LDL on PERK/elF2a/CHOP signaling pathway in vascular endothelial cells. Methods The effects of ox-LDL on PERK and p-elF2a protein expression of primary human umbilical vein endothelial cells （HUVECs） were investigated by Western blot analysis. PERK gene silencing and selective elF2a phosphatase inhibitor, salubrinal were used to inhibit the process of ox-LDL induced endothelial cell apoptosis, caspase-3 activity, and CHOP mRNA level. Results Ox-LDL treatment significantly increased the expression of PERK, PERK-mediated inactivation of elF2a phosphorylation, and the expression of CHOP, as well as the caspase-3 activity and apoptosis. The effects of ox-LDL were markedly decreased by knocking down PERK with stable transduction of lentiviral shRNA or by selective elF2a phosphatase inhibitor, salubrinal. Conclusion This study provides the first evidence that ox-LDL induces apoptosis in vascular endothelial cells mediated largely via the PERK/elF2a/CHOP ER-stress pathway. It adds new insights into the molecular mechanisms underlying the pathogenesis and progression of atherosclerosis.展开更多
Objective The mechanism through which platelet activating factor （PAF） induces cardiac electrical activity and arrhythmia is not well understood and previous studies have suggested a potential involvement of ion cha...Objective The mechanism through which platelet activating factor （PAF） induces cardiac electrical activity and arrhythmia is not well understood and previous studies have suggested a potential involvement of ion channels in its action. The present study was aimed to clarify the role of PAF in fatal arrhythmias following acute myocardia infarction （AMI） and the underlying mechanism. Methods （1） Blood PAF levels were measured among 72 AMI patients at the time of diagnosis with AMI and 48 h later, and their electrocardiogram （ECG） was recorded continuously. （2） Ischemia simulation and surface electrocardiogram were conducted in 20 pigs and their PAF levels were measured. （3） PAF perfusion and standard microelectrode recording were performed on guinea pig papillarymuscles. Results In both humans and pigs, elevated PAF levels were detected in AMI and simulated ischemia, respectively, and even higher PAF levels were found when fatal arrhythmias occurred. In guinea pig myocardium, PAF induced a shortening of action potential duration at 90% level of repolarization （APD 90 ）under non-ischemic conditions and a more pronounced shortening under early simulated ischemic conditions. Conclusion AMI and ischemia are associated with increased PAF levels in humans and pigs, which are further raised when fatal arrhythmia follows. The effects of PAF on the myocardium may be mediated by multiple ion channels.展开更多
Objective To investigate the incidence of falls and recurrent falls, and explore associated factors for single and recurrent falls among urban community-dwelling elderly in Beijing. Methods A cross-sectional study was...Objective To investigate the incidence of falls and recurrent falls, and explore associated factors for single and recurrent falls among urban community-dwelling elderly in Beijing. Methods A cross-sectional study was conducted in 472 elderly in the Longtan community of Dongcheng district, Beijing in 2009. Data regarding the incidence of fall and recurrent falls in the previous year, as well as associated factors were collected from the elderly through face-to-face interviews. Results The incidence of falls and recurrent falls was 17.8% and 6.1%, respectively, and it increased with age （X^2for trend=21.06, 19.20, P=0.001, 0.002）. Binary logistic stepwise regression analysis showed that age （OR=2.20）, living alone （OR=4.67） and gait disturbance （OR=1.27） were risk factors, while housing with elevators （OR=0.35）, appropriate width/height of stair steps （0R=0.78）, sufficient lighting for stairway （OR=0.45） and regular exercise （OR=0.12） could lower the risk for single fall; factors such as low monthly family income （OR=1.39）, poor vision （OR=1.83）, low physical ability （OR=4.47）, abnormal static balance （OR=2.48）, and fear of falls（OR=2.23） were risk factors, while appropriate width/height of stair steps （OR=0.49） and easiness of access to daily supplies （OR=0.41） were protective factors for recurrent falls. Conclusion The incidence of falls in commun and their related injuries have been associated ty-dwelling elderly people in Beijing is common, and falls with both intrinsic and extrinsic factors.展开更多
Vascular endothelium refers to a single layer of endothelial cells that line the inner surface of blood vessels,serving as barriers and transducers between the circulating blood in the lumen and the rest of the vessel...Vascular endothelium refers to a single layer of endothelial cells that line the inner surface of blood vessels,serving as barriers and transducers between the circulating blood in the lumen and the rest of the vessel wall.Endothelial cells play essential roles in many aspects of vascular biology,such as barrier functions,thrombosis/fibrinolysis,inflammation,angiogenesis,vasoconstriction and vasodilation.展开更多
Septic shock is a common critical condition, for which effective early fluid resuscitation is the therapeutic focus. According to the 2008 international guidelines for management of severe sepsis and septic shock, res...Septic shock is a common critical condition, for which effective early fluid resuscitation is the therapeutic focus. According to the 2008 international guidelines for management of severe sepsis and septic shock, resuscitation should achieve a central venous pressure （CVP） of 8-12 mmHg within the first 6 h. However, it is still uncertain about the sensitivity and specificity of CVP in reflecting the cardiac preload. Ultrasonography is a simple, rapid, non-invasive, and repeatable method for the measurement of sensitivity and specificity of CVP and has thus gradually attracted the increasing attention of physicians. It was reported that ultrasonography can show the inferior vena cava diameter, respiratory variability index, and blood volume in patients with sepsis or heart failure.展开更多
基金State Key Clinical Specialty Construction Project,China
文摘Objective PERK/elF2/CHOP is a major signaling pathway mediating endoplasmic reticulum （ER） stress related with atherosclerosis. Oxidized LDL （ox-LDL） also induces endothelial apoptosis and plays a vital role in the initiation and progression of atherosclerosis. The present study was conducted to explore the regulatory effect of ox-LDL on PERK/elF2a/CHOP signaling pathway in vascular endothelial cells. Methods The effects of ox-LDL on PERK and p-elF2a protein expression of primary human umbilical vein endothelial cells （HUVECs） were investigated by Western blot analysis. PERK gene silencing and selective elF2a phosphatase inhibitor, salubrinal were used to inhibit the process of ox-LDL induced endothelial cell apoptosis, caspase-3 activity, and CHOP mRNA level. Results Ox-LDL treatment significantly increased the expression of PERK, PERK-mediated inactivation of elF2a phosphorylation, and the expression of CHOP, as well as the caspase-3 activity and apoptosis. The effects of ox-LDL were markedly decreased by knocking down PERK with stable transduction of lentiviral shRNA or by selective elF2a phosphatase inhibitor, salubrinal. Conclusion This study provides the first evidence that ox-LDL induces apoptosis in vascular endothelial cells mediated largely via the PERK/elF2a/CHOP ER-stress pathway. It adds new insights into the molecular mechanisms underlying the pathogenesis and progression of atherosclerosis.
文摘Objective The mechanism through which platelet activating factor （PAF） induces cardiac electrical activity and arrhythmia is not well understood and previous studies have suggested a potential involvement of ion channels in its action. The present study was aimed to clarify the role of PAF in fatal arrhythmias following acute myocardia infarction （AMI） and the underlying mechanism. Methods （1） Blood PAF levels were measured among 72 AMI patients at the time of diagnosis with AMI and 48 h later, and their electrocardiogram （ECG） was recorded continuously. （2） Ischemia simulation and surface electrocardiogram were conducted in 20 pigs and their PAF levels were measured. （3） PAF perfusion and standard microelectrode recording were performed on guinea pig papillarymuscles. Results In both humans and pigs, elevated PAF levels were detected in AMI and simulated ischemia, respectively, and even higher PAF levels were found when fatal arrhythmias occurred. In guinea pig myocardium, PAF induced a shortening of action potential duration at 90% level of repolarization （APD 90 ）under non-ischemic conditions and a more pronounced shortening under early simulated ischemic conditions. Conclusion AMI and ischemia are associated with increased PAF levels in humans and pigs, which are further raised when fatal arrhythmia follows. The effects of PAF on the myocardium may be mediated by multiple ion channels.
基金supported by the National Health and Family Planning Commission of the People’s Republic of China,No.W2013BJ02
文摘Objective To investigate the incidence of falls and recurrent falls, and explore associated factors for single and recurrent falls among urban community-dwelling elderly in Beijing. Methods A cross-sectional study was conducted in 472 elderly in the Longtan community of Dongcheng district, Beijing in 2009. Data regarding the incidence of fall and recurrent falls in the previous year, as well as associated factors were collected from the elderly through face-to-face interviews. Results The incidence of falls and recurrent falls was 17.8% and 6.1%, respectively, and it increased with age （X^2for trend=21.06, 19.20, P=0.001, 0.002）. Binary logistic stepwise regression analysis showed that age （OR=2.20）, living alone （OR=4.67） and gait disturbance （OR=1.27） were risk factors, while housing with elevators （OR=0.35）, appropriate width/height of stair steps （0R=0.78）, sufficient lighting for stairway （OR=0.45） and regular exercise （OR=0.12） could lower the risk for single fall; factors such as low monthly family income （OR=1.39）, poor vision （OR=1.83）, low physical ability （OR=4.47）, abnormal static balance （OR=2.48）, and fear of falls（OR=2.23） were risk factors, while appropriate width/height of stair steps （OR=0.49） and easiness of access to daily supplies （OR=0.41） were protective factors for recurrent falls. Conclusion The incidence of falls in commun and their related injuries have been associated ty-dwelling elderly people in Beijing is common, and falls with both intrinsic and extrinsic factors.
基金funded by Beijing Science and Technology Commission Foundation[Z151100004015071]
文摘Vascular endothelium refers to a single layer of endothelial cells that line the inner surface of blood vessels,serving as barriers and transducers between the circulating blood in the lumen and the rest of the vessel wall.Endothelial cells play essential roles in many aspects of vascular biology,such as barrier functions,thrombosis/fibrinolysis,inflammation,angiogenesis,vasoconstriction and vasodilation.
文摘Septic shock is a common critical condition, for which effective early fluid resuscitation is the therapeutic focus. According to the 2008 international guidelines for management of severe sepsis and septic shock, resuscitation should achieve a central venous pressure （CVP） of 8-12 mmHg within the first 6 h. However, it is still uncertain about the sensitivity and specificity of CVP in reflecting the cardiac preload. Ultrasonography is a simple, rapid, non-invasive, and repeatable method for the measurement of sensitivity and specificity of CVP and has thus gradually attracted the increasing attention of physicians. It was reported that ultrasonography can show the inferior vena cava diameter, respiratory variability index, and blood volume in patients with sepsis or heart failure.
