Background:The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3,apoptosis-associated speck-like protein containing CARD (ASC),and caspase-1 is engaged in the...Background:The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3,apoptosis-associated speck-like protein containing CARD (ASC),and caspase-1 is engaged in the inflammatory response of many kidney diseases and can be activated by purinergic 2X7 receptor (P2X7R).This study was conducted to explore whether P2X7R plays a pathogenic role in the podocyte damage of obesity-related glomerulopathy (ORG) and whether this role is mediated by the activation ofNLRP3 inflammasome.Methods:A mouse model of ORG was established by high-fat diet feeding.The conditionally immortalized mouse podocytes were cultured with leptin or with leptin and P2X7R antagonist (KN-62 or A438079).The mRNA and protein expression of the P2X7R and NLRP3 inflammasome components including NLRP3,ASC,and caspase-1,as well as the podocyte-associated molecules including nephrin,podocin,and desmin in mouse renal cortex or cultured mouse podocytes were tested by real-time-polymerase chain reaction and Westem blot analysis,respectively.Results:The significantly upregulated expression of P2X7R and NLRP3 inflammasome components and the NLRP3 inflammasome activation were observed in the renal cortex (in fact their location in podocytes was proved by confocal microscopy) of ORG mice in vivo,which were accompanied with the morphological changes of podocyte damage and the expression changes of podocyte-associated molecules.Similar changes in the expression of P2X7R and NLRP3 inflammasome components as well as in the expression ofpodocyte-associated molecules were also observed in the cultured podocyte studies treated by leptin in vitro,and all of the above changes were significantly attenuated by the P2X7R antagonist KN-62 or A438079.Conclusions:P2X7R could trigger the activation ofNLRP3 inflammasome,and the activated P2X7R/NLRP3 inflammasome in podocytes might be involved in the podocyte damage of ORG.展开更多
Background:Post hoc analysis of the landmark atrial fibrillation follow-up investigation of rhythm management trial revealed that amiodarone was associated with higher risks of mortality,intensive care unit admission,...Background:Post hoc analysis of the landmark atrial fibrillation follow-up investigation of rhythm management trial revealed that amiodarone was associated with higher risks of mortality,intensive care unit admission,and non-cardiovascular death.We aim to evaluate the association between amiodarone use and patient survival under updated medical mode and level using data from the China Atrial Fibrillation(China-AF)Registry study.Methods:Clinical data of 8161 non-valvular atrial fibrillation(NVAF)patients who were antiarrhythmic drug(AAD)-naive before enrollment into the China-AF Registry,recruited between August 2011 and February 2017,were collected.The primary outcome was all-cause mortality.A Cox proportional hazard regression model was used to evaluate the association between amiodarone use and the outcome.We also calculated the rate of sinus rhythm maintenance at the penultimate follow-up.Results:Compared with 6167 patients of non-AAD group,689 patients of the amiodarone group were younger(mean age 65.6vs.68.6 years),more frequently completed high school education,had fewer comorbidities such as chronic heart failure,prior bleeding,and stroke,and were more likely to be treated in tertiary hospitals while less hospitalization.The proportion of persistent AF was much lower among users of amiodarone,who were also less likely to be taking oral anticoagulants.The patients in the amiodarone group had a statistically insignificant lower incidence of all-cause mortality(2.44vs.3.91 per 100 person-years)over a mean follow-up duration of 300.6±77.5 days.After adjusting for potential confounders,amiodarone use was not significantly associated with a lower risk of all-cause mortality(adjusted hazard ratio,0.79;95%confidence interval,0.42-1.49).Sub-group analysis revealed the consistent results.The rate of sinus rhythm maintenance at the penultimate follow-up in the amiodarone group was significantly higher than in the non-AAD group.Conclusions:Our study indicated that amiodarone use was not significantly associated with a lower risk of 1-year all-cause mortality compared with a non-AAD strategy in"real-world"patients with NVAF.展开更多
To the Editor:As acute coronary syndromes(ACS)is common causes of morbidity and mortality in China,they serve as an important case example to assess the impact of these health reforms on the quality,safety,and efficie...To the Editor:As acute coronary syndromes(ACS)is common causes of morbidity and mortality in China,they serve as an important case example to assess the impact of these health reforms on the quality,safety,and efficiency of healthcare.[1]ACS comprises a wide spectrum of disease subgroups,including ST-segment elevation myocardial infarction(STEMI),unstable angina(UA),and non-ST-segment elevation myocardial infarction(NSTEMI).Previous studies have shown increases in the intensity of testing and treatment while stable in-hospital mortality for STEMI in China between 2001 and 2011.[2]As non-ST-segment elevation acute coronary syndrome(NSTE-ACS)patients,who account for about two-thirds of ACS patients,have a wide spectrum of disease severity,risk-stratified management is recommended to ensure appropriate allocation of resources,especially in limited-resource settings of China.As limited data exist on the use of medical services and clinical outcomes in relation to health reforms,we aimed to determine temporal trends in diagnosis,treatment,and outcome for hospitalized NSTE-ACS patients in three regions of China between 2008 and 2015.展开更多
基金grants from the National Natural Science Foundation of China (No.81573745and No.8160140274)Beijing Municipal Natural Science Foundation (No.7172066) Beijing Development Foundation of Traditional Chinese Medicine (QN2016-23).
文摘Background:The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3,apoptosis-associated speck-like protein containing CARD (ASC),and caspase-1 is engaged in the inflammatory response of many kidney diseases and can be activated by purinergic 2X7 receptor (P2X7R).This study was conducted to explore whether P2X7R plays a pathogenic role in the podocyte damage of obesity-related glomerulopathy (ORG) and whether this role is mediated by the activation ofNLRP3 inflammasome.Methods:A mouse model of ORG was established by high-fat diet feeding.The conditionally immortalized mouse podocytes were cultured with leptin or with leptin and P2X7R antagonist (KN-62 or A438079).The mRNA and protein expression of the P2X7R and NLRP3 inflammasome components including NLRP3,ASC,and caspase-1,as well as the podocyte-associated molecules including nephrin,podocin,and desmin in mouse renal cortex or cultured mouse podocytes were tested by real-time-polymerase chain reaction and Westem blot analysis,respectively.Results:The significantly upregulated expression of P2X7R and NLRP3 inflammasome components and the NLRP3 inflammasome activation were observed in the renal cortex (in fact their location in podocytes was proved by confocal microscopy) of ORG mice in vivo,which were accompanied with the morphological changes of podocyte damage and the expression changes of podocyte-associated molecules.Similar changes in the expression of P2X7R and NLRP3 inflammasome components as well as in the expression ofpodocyte-associated molecules were also observed in the cultured podocyte studies treated by leptin in vitro,and all of the above changes were significantly attenuated by the P2X7R antagonist KN-62 or A438079.Conclusions:P2X7R could trigger the activation ofNLRP3 inflammasome,and the activated P2X7R/NLRP3 inflammasome in podocytes might be involved in the podocyte damage of ORG.
基金National Key Research and Development Program of China(2016YFC0900901,2016YFC1301002,2017YFC0908803,2018YFC1312501)National Science Foundation of China(81530016)。
文摘Background:Post hoc analysis of the landmark atrial fibrillation follow-up investigation of rhythm management trial revealed that amiodarone was associated with higher risks of mortality,intensive care unit admission,and non-cardiovascular death.We aim to evaluate the association between amiodarone use and patient survival under updated medical mode and level using data from the China Atrial Fibrillation(China-AF)Registry study.Methods:Clinical data of 8161 non-valvular atrial fibrillation(NVAF)patients who were antiarrhythmic drug(AAD)-naive before enrollment into the China-AF Registry,recruited between August 2011 and February 2017,were collected.The primary outcome was all-cause mortality.A Cox proportional hazard regression model was used to evaluate the association between amiodarone use and the outcome.We also calculated the rate of sinus rhythm maintenance at the penultimate follow-up.Results:Compared with 6167 patients of non-AAD group,689 patients of the amiodarone group were younger(mean age 65.6vs.68.6 years),more frequently completed high school education,had fewer comorbidities such as chronic heart failure,prior bleeding,and stroke,and were more likely to be treated in tertiary hospitals while less hospitalization.The proportion of persistent AF was much lower among users of amiodarone,who were also less likely to be taking oral anticoagulants.The patients in the amiodarone group had a statistically insignificant lower incidence of all-cause mortality(2.44vs.3.91 per 100 person-years)over a mean follow-up duration of 300.6±77.5 days.After adjusting for potential confounders,amiodarone use was not significantly associated with a lower risk of all-cause mortality(adjusted hazard ratio,0.79;95%confidence interval,0.42-1.49).Sub-group analysis revealed the consistent results.The rate of sinus rhythm maintenance at the penultimate follow-up in the amiodarone group was significantly higher than in the non-AAD group.Conclusions:Our study indicated that amiodarone use was not significantly associated with a lower risk of 1-year all-cause mortality compared with a non-AAD strategy in"real-world"patients with NVAF.
基金the National Key Research and Development Program of the Ministry of Science and Technology of China(2020YFC2004803)the Beijing Municipal Commission of Science and Technology(No.D171100006817001).
文摘To the Editor:As acute coronary syndromes(ACS)is common causes of morbidity and mortality in China,they serve as an important case example to assess the impact of these health reforms on the quality,safety,and efficiency of healthcare.[1]ACS comprises a wide spectrum of disease subgroups,including ST-segment elevation myocardial infarction(STEMI),unstable angina(UA),and non-ST-segment elevation myocardial infarction(NSTEMI).Previous studies have shown increases in the intensity of testing and treatment while stable in-hospital mortality for STEMI in China between 2001 and 2011.[2]As non-ST-segment elevation acute coronary syndrome(NSTE-ACS)patients,who account for about two-thirds of ACS patients,have a wide spectrum of disease severity,risk-stratified management is recommended to ensure appropriate allocation of resources,especially in limited-resource settings of China.As limited data exist on the use of medical services and clinical outcomes in relation to health reforms,we aimed to determine temporal trends in diagnosis,treatment,and outcome for hospitalized NSTE-ACS patients in three regions of China between 2008 and 2015.
