To the Editor:Thrombotic microangiopathy(TMA)is an uncommon hematological involvement in systemic lupus erythematosus(SLE)patients with an estimated incidence of 0.5–1.0%,including but not limited to thrombotic throm...To the Editor:Thrombotic microangiopathy(TMA)is an uncommon hematological involvement in systemic lupus erythematosus(SLE)patients with an estimated incidence of 0.5–1.0%,including but not limited to thrombotic thrombocytopenic purpura(TTP),hemolytic uremic syndrome(HUS),and other secondary conditions.SLE-TMA has a rapid onset and poor prognosis,manifesting as microvascular thrombosis,thrombocytopenia,and microangiopathic hemolytic anemia.[1]Based on the Chinese SLE Treatment and Research Group(CSTAR)registry,we aimed to summarize clinical characteristics and explore prognostic risk factors in SLE-TMA patients through a retrospective multicenter study.展开更多
南极Dome A被认为是地球上最好的天文观测台址,研制一台用于测光和台址测量的南极小望远镜的课题由此产生。CSTAR(Chinese Small Telescope ARray)于2006年8月提出,用时一年研制成功,并于2007年11月启程运往南极。文章运用振动理论并辅...南极Dome A被认为是地球上最好的天文观测台址,研制一台用于测光和台址测量的南极小望远镜的课题由此产生。CSTAR(Chinese Small Telescope ARray)于2006年8月提出,用时一年研制成功,并于2007年11月启程运往南极。文章运用振动理论并辅以ANSYS有限元分析软件,设计了该望远镜的抗振运输箱并通过实验加以验证。展开更多
Pulmonary arterial hypertension(PAH)is a severe complication of sys-temic lupus erythematosus(SLE),associated with right heart failure and high mortality.This study investigates SLE-PAH pathogenesis using the CSTAR co...Pulmonary arterial hypertension(PAH)is a severe complication of sys-temic lupus erythematosus(SLE),associated with right heart failure and high mortality.This study investigates SLE-PAH pathogenesis using the CSTAR cohort and whole-exome sequencing.Gene-based burden analysis of SLE-PAH patients(n=241),SLE-nonPAH patients(n=736),and healthy controls(n=996)identified rare TRAF5 coding variants in 3.78%of SLE-PAH cases(9/238)compared with 1.37%in SLE-nonPAH(10/728;95%CI,1.133–8.030,p=0.029)and 1.13%in healthy controls(11/977,95%CI,1.414–8.427,p=0.008).TRAF5 expression was signifi-cantly reduced in SLE-PAH variant carriers compared with SLE-PAH non-carriers or SLE-nonPAH patients(p<0.01).TRAF5 knockout mice ex-hibited more severe pulmonary hypertension,right ventricular hypertro-phy,and increased early mortality compared with wild-type mice.Sin-gle-cell RNA sequencing of lung tissue from knockout mice revealed reduced TRAF5 expression and increased apoptosis in arterial endothelial cells(ECs),with BMP/TGF-βpathway activation.In vitro studies confirmed that TRAF5 deficiency impaired the functions of pulmonary arterial ECs.Moreover,endothelium-specific TRAF5 overexpression in an SLE-PAH mouse model attenuated pulmonary hypertension.These findings suggest that TRAF5 loss-of-function exacerbates SLE-PAH by inducing EC dysfunction via the BMP/TGF-βsignaling,suggesting potential therapeutic targets.展开更多
基金supported by the Chinese National Key Technology R&D Program,Ministry of Science and Technology(No.2021YFC2501300)Beijing Municipal Science&Technology Commission(Nos.Z201100005520022,Z201100005520023,Z201100005520025,Z201100005520026,and Z201100005520027)+2 种基金CAMS Innovation Fund for Medical Sciences(CIFMS)(Nos.2021-I2M-1-005,2022-I2M-1-004,and 2023-I2M-2-005)National High-Level Hospital Clinical Research Funding(Nos.2022-PUMCH-B-013,2022-PUMCH-C-002,and 2022-PUMCH-D-009)Peking Union Medical College Student Innovation Training Project(No.2023zg1c06017).
文摘To the Editor:Thrombotic microangiopathy(TMA)is an uncommon hematological involvement in systemic lupus erythematosus(SLE)patients with an estimated incidence of 0.5–1.0%,including but not limited to thrombotic thrombocytopenic purpura(TTP),hemolytic uremic syndrome(HUS),and other secondary conditions.SLE-TMA has a rapid onset and poor prognosis,manifesting as microvascular thrombosis,thrombocytopenia,and microangiopathic hemolytic anemia.[1]Based on the Chinese SLE Treatment and Research Group(CSTAR)registry,we aimed to summarize clinical characteristics and explore prognostic risk factors in SLE-TMA patients through a retrospective multicenter study.
文摘南极Dome A被认为是地球上最好的天文观测台址,研制一台用于测光和台址测量的南极小望远镜的课题由此产生。CSTAR(Chinese Small Telescope ARray)于2006年8月提出,用时一年研制成功,并于2007年11月启程运往南极。文章运用振动理论并辅以ANSYS有限元分析软件,设计了该望远镜的抗振运输箱并通过实验加以验证。
基金supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project(2024ZD 0526700 and 2024ZD0526701)the National Natural Science Foundation of China(nos.82271855,82241019,82073853)+2 种基金CAMS Innovation Fund for Medical Sciences(nos.2021-I2M-1-005 and 2022-I2M-1-004)National High Level Hospital Clinical Research Funding(2022-PUMCH-B-013,C-002,D-009)Beijing Natural Science Foundation(nos.7244387 and 7242202).
文摘Pulmonary arterial hypertension(PAH)is a severe complication of sys-temic lupus erythematosus(SLE),associated with right heart failure and high mortality.This study investigates SLE-PAH pathogenesis using the CSTAR cohort and whole-exome sequencing.Gene-based burden analysis of SLE-PAH patients(n=241),SLE-nonPAH patients(n=736),and healthy controls(n=996)identified rare TRAF5 coding variants in 3.78%of SLE-PAH cases(9/238)compared with 1.37%in SLE-nonPAH(10/728;95%CI,1.133–8.030,p=0.029)and 1.13%in healthy controls(11/977,95%CI,1.414–8.427,p=0.008).TRAF5 expression was signifi-cantly reduced in SLE-PAH variant carriers compared with SLE-PAH non-carriers or SLE-nonPAH patients(p<0.01).TRAF5 knockout mice ex-hibited more severe pulmonary hypertension,right ventricular hypertro-phy,and increased early mortality compared with wild-type mice.Sin-gle-cell RNA sequencing of lung tissue from knockout mice revealed reduced TRAF5 expression and increased apoptosis in arterial endothelial cells(ECs),with BMP/TGF-βpathway activation.In vitro studies confirmed that TRAF5 deficiency impaired the functions of pulmonary arterial ECs.Moreover,endothelium-specific TRAF5 overexpression in an SLE-PAH mouse model attenuated pulmonary hypertension.These findings suggest that TRAF5 loss-of-function exacerbates SLE-PAH by inducing EC dysfunction via the BMP/TGF-βsignaling,suggesting potential therapeutic targets.
