Microglia are the main non-neuronal cells in the central nervous system that have important roles in brain development and functional connectivity of neural circuits.In brain physiology,highly dynamic microglial proce...Microglia are the main non-neuronal cells in the central nervous system that have important roles in brain development and functional connectivity of neural circuits.In brain physiology,highly dynamic microglial processes are facilitated to sense the surrounding environment and stimuli.Once the brain switches its functional states,microglia are recruited to specific sites to exert their immune functions,including the release of cytokines and phagocytosis of cellular debris.The crosstalk of microglia between neurons,neural stem cells,endothelial cells,oligodendrocytes,and astrocytes contributes to their functions in synapse pruning,neurogenesis,vascularization,myelination,and blood-brain barrier permeability.In this review,we highlight the neuron-derived“find-me,”“eat-me,”and“don't eat-me”molecular signals that drive microglia in response to changes in neuronal activity for synapse refinement during brain development.This review reveals the molecular mechanism of neuron-microglia interaction in synaptic pruning and presents novel ideas for the synaptic pruning of microglia in disease,thereby providing important clues for discovery of target drugs and development of nervous system disease treatment methods targeting synaptic dysfunction.展开更多
Objective:This study aims to evaluate the morphology and function of the aortic valve after transcatheter closure of ventricular septal defect(VSD)with aortic valve prolapse(AVP)abased on clinical and radiological out...Objective:This study aims to evaluate the morphology and function of the aortic valve after transcatheter closure of ventricular septal defect(VSD)with aortic valve prolapse(AVP)abased on clinical and radiological outcomes.Methods:From January 2013 to November 2014,164 consecutive patients(97 males,59.1%)with VSD and AVP were treated by transcatheter closure.The patients were divided into the mild AVP group(n=63),moderate AVP group(n=89)and severe AVP group(n=12).The clinical and radiological outcomes of these patients were analyzed retrospectively.Results:In total,146(89.0%)patients were successfully treated with VSD occluders,including 59/63(93.7%)with mild AVP,80/89(89.9%)with moderate AVP and 7/12(58.3%)with severe AVP.The degree of AVP was ameliorated or disappeared in 39(26.7%)patients,and remained unchanged in 103(70.5%)patients after the intervention.In the 35 patients who initially had trivial-to-moderate aortic regurgitation(AR),the degree of AR was ameliorated or disappeared in 25(71.4%)patients,aggravated from trivial to mild AR in 1(2.9%)patient,and remained unchanged in 9(25.7%)patients.In 111 patients without AR,1(0.9%)patient had mild AR and 24(21.6%)patients had trivial AR after intervention.The depth and width of the prolapsed aortic valve decreased after transcatheter closure of VSD in all three groups.During the 70-month(range,54–77)follow-up period,no patients with AVP and AR needed an aortic valve intervention.Conclusions:Transcatheter closure of VSD with AVP is feasible.The morphology and function of the prolapsed aortic valve improved and remained stable for a long period after intervention.展开更多
Background：Autophagy has been found to be involved in animal and cell models ofatherosclerosis,but to date,it lacks general observation in human atherosclerotic plaques.Here,we investigated autophagy in smooth muscle...Background：Autophagy has been found to be involved in animal and cell models ofatherosclerosis,but to date,it lacks general observation in human atherosclerotic plaques.Here,we investigated autophagy in smooth muscle cells （SMCs）,endothelial cells （ECs）,and macrophages in human atherosclerotic plaques via transmission electron microscopy （TEM）,western blotting,and immunohistochemistry analysis.Methods：The histopathologic morphology of these plaques was observed via hematoxylin and eosin staining.The ultrastructural morphology of the SMCs,ECs,and macrophages in these plaques was observed via TEM.The localization ofmicrotubule-associated protein 1 light chain 3 （MAP 1-LC3）,a relatively special maker ofautophagy,in plaques was observed by double fluorescent immunochemistty and western blotting.Results：All of these human atherosclerotic plaques were considered advanced and unstable in histologically observation.By double fluorescent immunochemistry,the expression of LC3-Ⅱ increased in the SMCs of the fibrous cap,the macrophages,and the microvascular ECs of the plaque shoulders.The protein level of LC3-Ⅱ by western blotting significantly increased in plaques compared with normal controls.In addition,TEM observation of plaques revealed certain features of autophagy in SMCs,ECs,and macrophages including the formation of myelin figures,vacuolization,and the accumulation of inclusions in the cytosol.These results indicate that autophagy is activated in SMCs,ECs,and macrophages in human advanced atherosclerotic plaques.Conclusions：Our study is to demonstrate the existence of autophagy in human atherosclerotic plaques by different methods,which may contribute to the development of pharmacological approaches to stabilize vulnerable and rupture-prone lesions.展开更多
基金supported by the National Natural Science Foundation of ChinaNo.32200778(to QC)+5 种基金the Natural Science Foundation of Jiangsu ProvinceNo.BK20220494(to QC)Suzhou Medical and Health Technology Innovation ProjectNo.SKY2022107(to QC)a grant from the Clinical Research Center of Neurological Disease in The Second Affiliated Hospital of Soochow UniversityNos.ND2022A04(to QC)and ND2023B06(to JS)。
文摘Microglia are the main non-neuronal cells in the central nervous system that have important roles in brain development and functional connectivity of neural circuits.In brain physiology,highly dynamic microglial processes are facilitated to sense the surrounding environment and stimuli.Once the brain switches its functional states,microglia are recruited to specific sites to exert their immune functions,including the release of cytokines and phagocytosis of cellular debris.The crosstalk of microglia between neurons,neural stem cells,endothelial cells,oligodendrocytes,and astrocytes contributes to their functions in synapse pruning,neurogenesis,vascularization,myelination,and blood-brain barrier permeability.In this review,we highlight the neuron-derived“find-me,”“eat-me,”and“don't eat-me”molecular signals that drive microglia in response to changes in neuronal activity for synapse refinement during brain development.This review reveals the molecular mechanism of neuron-microglia interaction in synaptic pruning and presents novel ideas for the synaptic pruning of microglia in disease,thereby providing important clues for discovery of target drugs and development of nervous system disease treatment methods targeting synaptic dysfunction.
基金This study was reviewed and approved by the Institutional Review Board of Guangdong Province People’s Hospital(Guangzhou,Guangdong,China)(No.GDREC2020213H)This study was supported by National Key R&D Program of China(Grant No.2016YFC1100305)Sanming Medical Project of China(Grant No.SZSM201612057).
文摘Objective:This study aims to evaluate the morphology and function of the aortic valve after transcatheter closure of ventricular septal defect(VSD)with aortic valve prolapse(AVP)abased on clinical and radiological outcomes.Methods:From January 2013 to November 2014,164 consecutive patients(97 males,59.1%)with VSD and AVP were treated by transcatheter closure.The patients were divided into the mild AVP group(n=63),moderate AVP group(n=89)and severe AVP group(n=12).The clinical and radiological outcomes of these patients were analyzed retrospectively.Results:In total,146(89.0%)patients were successfully treated with VSD occluders,including 59/63(93.7%)with mild AVP,80/89(89.9%)with moderate AVP and 7/12(58.3%)with severe AVP.The degree of AVP was ameliorated or disappeared in 39(26.7%)patients,and remained unchanged in 103(70.5%)patients after the intervention.In the 35 patients who initially had trivial-to-moderate aortic regurgitation(AR),the degree of AR was ameliorated or disappeared in 25(71.4%)patients,aggravated from trivial to mild AR in 1(2.9%)patient,and remained unchanged in 9(25.7%)patients.In 111 patients without AR,1(0.9%)patient had mild AR and 24(21.6%)patients had trivial AR after intervention.The depth and width of the prolapsed aortic valve decreased after transcatheter closure of VSD in all three groups.During the 70-month(range,54–77)follow-up period,no patients with AVP and AR needed an aortic valve intervention.Conclusions:Transcatheter closure of VSD with AVP is feasible.The morphology and function of the prolapsed aortic valve improved and remained stable for a long period after intervention.
文摘Background：Autophagy has been found to be involved in animal and cell models ofatherosclerosis,but to date,it lacks general observation in human atherosclerotic plaques.Here,we investigated autophagy in smooth muscle cells （SMCs）,endothelial cells （ECs）,and macrophages in human atherosclerotic plaques via transmission electron microscopy （TEM）,western blotting,and immunohistochemistry analysis.Methods：The histopathologic morphology of these plaques was observed via hematoxylin and eosin staining.The ultrastructural morphology of the SMCs,ECs,and macrophages in these plaques was observed via TEM.The localization ofmicrotubule-associated protein 1 light chain 3 （MAP 1-LC3）,a relatively special maker ofautophagy,in plaques was observed by double fluorescent immunochemistty and western blotting.Results：All of these human atherosclerotic plaques were considered advanced and unstable in histologically observation.By double fluorescent immunochemistry,the expression of LC3-Ⅱ increased in the SMCs of the fibrous cap,the macrophages,and the microvascular ECs of the plaque shoulders.The protein level of LC3-Ⅱ by western blotting significantly increased in plaques compared with normal controls.In addition,TEM observation of plaques revealed certain features of autophagy in SMCs,ECs,and macrophages including the formation of myelin figures,vacuolization,and the accumulation of inclusions in the cytosol.These results indicate that autophagy is activated in SMCs,ECs,and macrophages in human advanced atherosclerotic plaques.Conclusions：Our study is to demonstrate the existence of autophagy in human atherosclerotic plaques by different methods,which may contribute to the development of pharmacological approaches to stabilize vulnerable and rupture-prone lesions.
