Kiehl and colleagues1 utilized data from the Osteoarthritis Initiative(OAI)to address a clinically significant question:Is lifetime participation in strength training(ST)associated with improved trajectories of pain,f...Kiehl and colleagues1 utilized data from the Osteoarthritis Initiative(OAI)to address a clinically significant question:Is lifetime participation in strength training(ST)associated with improved trajectories of pain,function,and mobility in individuals with knee osteoarthritis(OA)?Among 3192 participants,those classified as“Lifelong ST”(n=142)demonstrated superior 4-year patient-reported outcomes and exhibited the lowest incidence of mobility disability(0.8%vs 2.3%–4.1%).Notably,they also maintained the fastest walking speeds at Year 4.展开更多
Estrogen deficiency after menopause accelerates bone loss by stimulating osteoclast formation and activity,but the molecular pathways that link estrogen signaling to osteoclast regulation remain incompletely defined.H...Estrogen deficiency after menopause accelerates bone loss by stimulating osteoclast formation and activity,but the molecular pathways that link estrogen signaling to osteoclast regulation remain incompletely defined.Here,we identify the sialyltransferase ST3GAL-I as a key mediator of RANKL-induced osteoclastogenesis.RANKL activates c-FOS to drive ST3GAL1 transcription,whereas estrogen-bound ERαcompetes with TRAF6 and suppresses this c-FOS–dependent induction.In a clinical cohort of pre-menopausal and post-menopausal women with or without osteoporosis,serum total andα-2,3-linked sialic acid levels increased with age and were highest in post-menopausal osteoporotic patients.Single-cell RNA sequencing of human bone revealed that osteoclasts form a prominent cluster only after menopause,where FOS,CTSK,and ST3GAL1 are strongly co-expressed,and the estrogen-responsive gene PGR is down-regulated.Additionally,in vivo experiments showed that sialidase treatment in estrogen-deficient models effectively reduced osteoclast-mediated bone loss,mimicking the effects of estradiol.These findings define a direct molecular link between loss of estrogen and activation of a FOS–ST3GAL1 sialylation pathway in osteoclasts,providing mechanistic insight into the enhanced bone resorption characteristic of post-menopausal osteoporosis.展开更多
目的探讨动态心电图参数联合心肌梗死溶栓疗法(TIMI)危险评分对急性ST段抬高型心肌梗死(STEMI)患者经皮冠状动脉介入治疗(PCI)术后发生主要不良心血管事件(MACE)的预测价值。方法选取2021年7月至2024年6月于连云港市第一人民医院就诊的S...目的探讨动态心电图参数联合心肌梗死溶栓疗法(TIMI)危险评分对急性ST段抬高型心肌梗死(STEMI)患者经皮冠状动脉介入治疗(PCI)术后发生主要不良心血管事件(MACE)的预测价值。方法选取2021年7月至2024年6月于连云港市第一人民医院就诊的STEMI患者119例,根据术后1年随访期内是否发生MACE分为发生组(24例)和未发生组(95例)。比较两组一般临床资料、动态心电图参数;采用多因素Logistic回归分析STEMI患者PCI术后发生MACE的影响因素;采用ROC曲线分析动态心电图参数[包括24 h QT间期变异性(24 h QTV)、窦性心搏RR间期的标准差(SDNN)等]、TIMI危险评分对STEMI患者PCI术后发生MACE的预测价值。结果发生组年龄、Killip心功能分级≥Ⅱ级、TIMI危险评分高于未发生组(P<0.05)。发生组24 h QTV、SDNN水平低于未发生组(P<0.001)。多因素Logistic回归分析显示,年龄、TIMI危险评分是STEMI患者PCI术后发生MACE的独立危险因素,24 h QTV、SDNN是STEMI患者PCI术后发生MACE的独立保护因素(OR=2.098,95%CI:1.022~4.307,P=0.044;OR=2.869,95%CI:1.267~6.497,P=0.012;OR=0.355,95%CI:0.159~0.795,P=0.012;OR=0.376,95%CI:0.174~0.813,P=0.013)。ROC曲线分析显示,24 h QTV、SDNN、TIMI危险评分预测STEMI患者PCI术后发生MACE的曲线下面积分别为0.762、0.740、0.761,联合检测预测的曲线下面积为0.930,显著优于单独检测(P<0.05)。结论动态心电图参数24 h QTV、SDNN及TIMI危险评分均是STEMI患者PCI术后发生MACE的独立影响因素,联合检测可较好地预测STEMI患者PCI术后MACE的发生。展开更多
文摘Kiehl and colleagues1 utilized data from the Osteoarthritis Initiative(OAI)to address a clinically significant question:Is lifetime participation in strength training(ST)associated with improved trajectories of pain,function,and mobility in individuals with knee osteoarthritis(OA)?Among 3192 participants,those classified as“Lifelong ST”(n=142)demonstrated superior 4-year patient-reported outcomes and exhibited the lowest incidence of mobility disability(0.8%vs 2.3%–4.1%).Notably,they also maintained the fastest walking speeds at Year 4.
基金funded by a grant from the National Natural Science Foundation of China(82572785,82172489,82172449)funding for young investigators of PLA(2022-JCJQ-QT-004)。
文摘Estrogen deficiency after menopause accelerates bone loss by stimulating osteoclast formation and activity,but the molecular pathways that link estrogen signaling to osteoclast regulation remain incompletely defined.Here,we identify the sialyltransferase ST3GAL-I as a key mediator of RANKL-induced osteoclastogenesis.RANKL activates c-FOS to drive ST3GAL1 transcription,whereas estrogen-bound ERαcompetes with TRAF6 and suppresses this c-FOS–dependent induction.In a clinical cohort of pre-menopausal and post-menopausal women with or without osteoporosis,serum total andα-2,3-linked sialic acid levels increased with age and were highest in post-menopausal osteoporotic patients.Single-cell RNA sequencing of human bone revealed that osteoclasts form a prominent cluster only after menopause,where FOS,CTSK,and ST3GAL1 are strongly co-expressed,and the estrogen-responsive gene PGR is down-regulated.Additionally,in vivo experiments showed that sialidase treatment in estrogen-deficient models effectively reduced osteoclast-mediated bone loss,mimicking the effects of estradiol.These findings define a direct molecular link between loss of estrogen and activation of a FOS–ST3GAL1 sialylation pathway in osteoclasts,providing mechanistic insight into the enhanced bone resorption characteristic of post-menopausal osteoporosis.
文摘目的探讨动态心电图参数联合心肌梗死溶栓疗法(TIMI)危险评分对急性ST段抬高型心肌梗死(STEMI)患者经皮冠状动脉介入治疗(PCI)术后发生主要不良心血管事件(MACE)的预测价值。方法选取2021年7月至2024年6月于连云港市第一人民医院就诊的STEMI患者119例,根据术后1年随访期内是否发生MACE分为发生组(24例)和未发生组(95例)。比较两组一般临床资料、动态心电图参数;采用多因素Logistic回归分析STEMI患者PCI术后发生MACE的影响因素;采用ROC曲线分析动态心电图参数[包括24 h QT间期变异性(24 h QTV)、窦性心搏RR间期的标准差(SDNN)等]、TIMI危险评分对STEMI患者PCI术后发生MACE的预测价值。结果发生组年龄、Killip心功能分级≥Ⅱ级、TIMI危险评分高于未发生组(P<0.05)。发生组24 h QTV、SDNN水平低于未发生组(P<0.001)。多因素Logistic回归分析显示,年龄、TIMI危险评分是STEMI患者PCI术后发生MACE的独立危险因素,24 h QTV、SDNN是STEMI患者PCI术后发生MACE的独立保护因素(OR=2.098,95%CI:1.022~4.307,P=0.044;OR=2.869,95%CI:1.267~6.497,P=0.012;OR=0.355,95%CI:0.159~0.795,P=0.012;OR=0.376,95%CI:0.174~0.813,P=0.013)。ROC曲线分析显示,24 h QTV、SDNN、TIMI危险评分预测STEMI患者PCI术后发生MACE的曲线下面积分别为0.762、0.740、0.761,联合检测预测的曲线下面积为0.930,显著优于单独检测(P<0.05)。结论动态心电图参数24 h QTV、SDNN及TIMI危险评分均是STEMI患者PCI术后发生MACE的独立影响因素,联合检测可较好地预测STEMI患者PCI术后MACE的发生。
