China faces the greatest challenge from stroke in the world.The death rate for cerebrovascular diseases in China was 149.49 per 100000,accounting for 1.57 million deaths in 2018.It ranked third among the leading cause...China faces the greatest challenge from stroke in the world.The death rate for cerebrovascular diseases in China was 149.49 per 100000,accounting for 1.57 million deaths in 2018.It ranked third among the leading causes of death behind malignant tumours and heart disease.The age-standardised prevalence and incidence of stroke in 2013 were 1114.8 per 100000 population and 246.8 per 100000 person-years,respectively.According to the Global Burden of Disease Study 2017,the years of life lost(YLLs)per 100000 population for stroke increased by 14.6%;YLLs due to stroke rose from third highest among all causes in 1990 to the highest in 2017.The absolute numbers and rates per 100000 population for all-age disability-adjusted life years(DALYs)for stroke increased substantially between 1990 and 2017,and stroke was the leading cause of all-age DALYs in 2017.The main contributors to cerebrovascular diseases include behavioural risk factors(smoking and alcohol use)and pre-existing conditions(hypertension,diabetes mellitus,dyslipidaemia and atrial fibrillation(AF)).The most prevalent risk factors among stroke survivors were hypertension(63.0%-84.2%)and smoking(31.7%-47.6%).The least prevalent was AF(2.7%-7.4%).The prevalences for major risk factors for stroke are high and most have increased over time.Based on the latest national epidemiological data,26.6%of adults aged≥15 years(307.6 million adults)smoked tobacco products.For those aged≥18 years,age-adjusted prevalence of hypertension was 25.2%;adjusted prevalence of hypercholesterolaemia was 5.8%;and the standardised prevalence of diabetes was 10.9%.For those aged≥40 years,the standardised prevalence of AF was 2.31%.Data from the Hospital Quality Monitoring System showed that 3010204 inpatients with stroke were admitted to 1853 tertiary care hospitals during 2018.Of those,2466785(81.9%)were ischaemic strokes(ISs);447609(14.9%)were intracerebral haemorrhages(ICHs);and 95810(3.2%)were subarachnoid haemorrhages(SAHs).The average age of patients admitted was 66 years old,and展开更多
This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder(ASD) in Chinese children.We targeted the population of 6 to 12-year-old children for this prevalence study by multis...This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder(ASD) in Chinese children.We targeted the population of 6 to 12-year-old children for this prevalence study by multistage convenient cluster sampling.The Modified Chinese Autism Spectrum Rating Scale was used for the screening process.Of the target population of 142,086 children,88.5%(n=125,806) participated in the study.A total of 363 children were confirmed as having ASD.The observed ASD prevalence rate was 0.29%(95% CI:0.26%-0.32%) for the overall population.After adjustment for response rates,the estimated number of ASD cases was867 in the target population sample,thereby achieving an estimated prevalence of 0.70%(95% CI:0.64%-0.74%).The prevalence was significantly higher in boys than in girls(0.95%;95% CI:0.87%-1.02% versus 0.30%;95%CI:0.26%-0.34%;P <0.001).Of the 363 confirmed ASD cases,43.3% were newly diagnosed,and most of those(90.4%) were attending regular schools,and 68.8% of the children with ASD had at least one neuropsychiatric comorbidity.Our findings provide reliable data on the estimated ASD prevalence and comorbidities in Chinese children.展开更多
The NLRP3 inflammasome is a cytosolic multiprotein complex composed of the innate immune receptor protein NLRP3,adapter protein ASC,and inflammatory protease caspase-1 that responds to microbial infection,endogenous d...The NLRP3 inflammasome is a cytosolic multiprotein complex composed of the innate immune receptor protein NLRP3,adapter protein ASC,and inflammatory protease caspase-1 that responds to microbial infection,endogenous danger signals,and environmental stimuli.The assembled NLRP3 inflammasome can activate the protease caspase‐1 to induce gasdermin D-dependent pyroptosis and facilitate the release of IL-1β and IL-18,which contribute to innate immune defense and homeostatic maintenance.However,aberrant activation of the NLRP3 inflammasome is associated with the pathogenesis of various inflammatory diseases,such as diabetes,cancer,and Alzheimer’s disease.Recent studies have revealed that NLRP3 inflammasome activation contributes to not only pyroptosis but also other types of cell death,including apoptosis,necroptosis,and ferroptosis.In addition,various effectors of cell death have been reported to regulate NLRP3 inflammasome activation,suggesting that cell death is closely related to NLRP3 inflammasome activation.In this review,we summarize the inextricable link between NLRP3 inflammasome activation and cell death and discuss potential therapeutics that target cell death effectors in NLRP3 inflammasome-associated diseases.展开更多
INTRODUCTIONThe transforming growth factor-β （TGF-β） superfamily com- prises TGF-βs, Activin, bone morphogenetic proteins （BMPs） and other related proteins. TGF-β superfamily members act through a heteromeric ...INTRODUCTIONThe transforming growth factor-β （TGF-β） superfamily com- prises TGF-βs, Activin, bone morphogenetic proteins （BMPs） and other related proteins. TGF-β superfamily members act through a heteromeric receptor complex,, comprised of type I and type II receptors at the cell surface that transduce intracellular signals via Smad complex or mitogen-activated protein kinase （MAPK） cascade.展开更多
Appropriate autophagy has protective effects on ischemic nerve tissue,while excessive autophagy may cause cell death.The inflammatory response plays an important role in the survival of nerve cells and the recovery of...Appropriate autophagy has protective effects on ischemic nerve tissue,while excessive autophagy may cause cell death.The inflammatory response plays an important role in the survival of nerve cells and the recovery of neural tissue after ischemia.Many studies have found an interaction between autophagy and inflammation in the pathogenesis of ischemic stroke.This study outlines recent advances regarding the role of autophagy in the post-stroke inflammatory response as follows.(1)Autophagy inhibits inflammatory responses caused by ischemic stimulation through mTOR,the AMPK pathway,and inhibition of inflammasome activation.(2)Activation of inflammation triggers the formation of autophagosomes,and the upregulation of autophagy levels is marked by a significant increase in the autophagy-forming markers LC3-II and Beclin-1.Lipopolysaccharide stimulates microglia and inhibits ULK1 activity by direct phosphorylation of p38 MAPK,reducing the flux and autophagy level,thereby inducing inflammatory activity.(3)By blocking the activation of autophagy,the activation of inflammasomes can alleviate cerebral ischemic injury.Autophagy can also regulate the phenotypic alternation of microglia through the nuclear factor-κB pathway,which is beneficial to the recovery of neural tissue after ischemia.Studies have shown that some drugs such as resveratrol can exert neuroprotective effects by regulating the autophagy-inflammatory pathway.These studies suggest that the autophagy-inflammatory pathway may provide a new direction for the treatment of ischemic stroke.展开更多
Artificial intelligence(AI)aims to mimic human cognitive functions.It is bringing a paradigm shift to healthcare,powered by increasing availability of healthcare data and rapid progress of analytics techniques.We surv...Artificial intelligence(AI)aims to mimic human cognitive functions.It is bringing a paradigm shift to healthcare,powered by increasing availability of healthcare data and rapid progress of analytics techniques.We survey the current status of AI applications in healthcare and discuss its future.AI can be applied to various types of healthcare data(structured and unstructured).Popular AI techniques include machine learning methods for structured data,such as the classical support vector machine and neural network,and the modern deep learning,as well as natural language processing for unstructured data.Major disease areas that use AI tools include cancer,neurology and cardiology.We then review in more details the AI applications in stroke,in the three major areas of early detection and diagnosis,treatment,as well as outcome prediction and prognosis evaluation.We conclude with discussion about pioneer AI systems,such as IBM Watson,and hurdles for real-life deployment of AI.展开更多
Cerebral small vessel disease(CSVD)is a very common neurological disease in older people.It causes stroke and dementia,mood disturbance and gait problems.Since it is difficult to visualise CSVD pathologies in vivo,the...Cerebral small vessel disease(CSVD)is a very common neurological disease in older people.It causes stroke and dementia,mood disturbance and gait problems.Since it is difficult to visualise CSVD pathologies in vivo,the diagnosis of CSVD has relied on imaging findings including white matter hyperintensities,lacunar ischaemic stroke,lacunes,microbleeds,visible perivascular spaces and many haemorrhagic strokes.However,variations in the use of definition and terms of these features have probably caused confusion and difficulties in interpreting results of previous studies.A standardised use of terms should be encouraged in CSVD research.These CSVD features have long been regarded as different lesions,but emerging evidence has indicated that they might share some common intrinsic microvascular pathologies and therefore,owing to its diffuse nature,CSVD should be regarded as a‘whole-brain disease’.Single antiplatelet(for acute lacunar ischaemic stroke)and management of traditional risk factors still remain the most important therapeutic and preventive approach,due to limited understanding of pathophysiology in CSVD.Increasing evidence suggests that new studies should consider drugs that target endothelium and blood–brain barrier to prevent and treat CSVD.Epidemiology of CSVD might differ in Asian compared with Western populations(where most results and guidelines about CSVD and stroke originate),but more community-based data and clear stratification of stroke types are required to address this.展开更多
Ischemic stroke is a leading cause of morbidity and mortality worldwide. Resident microglia are the principal immune cells of the brain, and the first to respond to the pathophysiological changes induced by ischemic s...Ischemic stroke is a leading cause of morbidity and mortality worldwide. Resident microglia are the principal immune cells of the brain, and the first to respond to the pathophysiological changes induced by ischemic stroke. Traditionally, it has been thought that microglial activation is deleterious in ischemic stroke, and therapies to suppress it have been intensively explored. However,increasing evidence suggests that microglial activation is also critical for neurogenesis, angiogenesis, and synaptic remodeling, thereby promoting functional recovery after cerebral ischemia. Here, we comprehensively review the dual role of microglia during the different phases of ischemic stroke, and the possible mechanisms controlling the post-ischemic activity of microglia. In addition, we discuss the dynamic interactions between microglia and other cells, such as neurons, astrocytes, oligodendrocytes,and endothelial cells within the brain parenchyma and the neurovascular unit.展开更多
Oxidative stress plays a significant role in the pathogenesis of Alzheimer＇s disease （AD）, a devastating disease of the elderly. The brain is more vulnerable than other organs to oxidative stress, and most of the c...Oxidative stress plays a significant role in the pathogenesis of Alzheimer＇s disease （AD）, a devastating disease of the elderly. The brain is more vulnerable than other organs to oxidative stress, and most of the components of neurons （lipids, proteins, and nucleic acids） can be oxidized in AD due to mitochondrial dysfunction, increased metal levels, inflammation, and β-amyloid （Aβ） peptides. Oxidative stress participates in the development of AD by promoting Aβ deposition, tau hyperphosphorylation, and the subsequent loss of synapses and neurons. The relationship between oxidative stress and AD suggests that oxidative stress is an essential part of the pathological process, and antioxidants may be useful for AD treatment.展开更多
Neuroinflammation is associated with neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease,ancamyotrophic lateral sclerosis.Microglia and astrocytes are key regulators of inflammatory resp...Neuroinflammation is associated with neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease,ancamyotrophic lateral sclerosis.Microglia and astrocytes are key regulators of inflammatory responses in the central nervous system.The activation of microglia and astrocytes is heterogeneous and traditionally categorized as neurotoxi(M1-phenotype microglia and A1-phenotype astrocytes)or neuroprotective(M2-phenotype microglia and A2-phenotype astrocytes).However,this dichotomized classification may not reflect the various phenotypes of microgliaand astrocytes.The relationship between these activated glial cells is also very complicated,and the phenotypic distribution can change,based on the progression of neurodegenerative diseases.A better understanding of the rolesof microglia and astrocytes in neurodegenerative diseases is essential for developing effective therapies.In this review,we discuss the roles of inflammatory response in neurodegenerative diseases,focusing on the contributions of microglia and astrocytes and their relationship.In addition,we discuss biomarkers to measure neuroinflammation andstudies on therapeutic drugs that can modulate neuroinflammation.展开更多
Objective：To systematically review the updated information about the gut microbiota-brain axis.Data Sources：All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literat...Objective：To systematically review the updated information about the gut microbiota-brain axis.Data Sources：All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literature search on PubMed,ScienceDirect,and Web of Science,with the keywords of＂gut microbiota＂,＂gut-brain axis＂,and ＂neuroscience＂.Study Selection：All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed,with no limitation of study design.Results：It is well-recognized that gut microbiota affects the brain＆#39;s physiological,behavioral,and cognitive functions although its precise mechanism has not yet been fully understood.Gut microbiota-brain axis may include gut microbiota and their metabolic products,enteric nervous system,sympathetic and parasympathetic branches within the autonomic nervous system,neural-immune system,neuroendocrine system,and central nervous system.Moreover,there may be five communication routes between gut microbiota and brain,including the gut-brain＆#39;s neural network,neuroendocrine-hypothalamic-pituitary-adrenal axis,gut immune system,some neurotransmitters and neural regulators synthesized by gut bacteria,and barrier paths including intestinal mucosal barrier and blood-brain barrier.The microbiome is used to define the composition and functional characteristics of gut microbiota,and metagenomics is an appropriate technique to characterize gut microbiota.Conclusions：Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain,which may provide a new way to protect the brain in the near future.展开更多
Background DI-3-n-butylphthalide （NBP）, first isolated from the seeds of celery, showed efficacy in animal models of stroke. This study was a clinical trial to assess the efficacy and safety of NBP with a continuous...Background DI-3-n-butylphthalide （NBP）, first isolated from the seeds of celery, showed efficacy in animal models of stroke. This study was a clinical trial to assess the efficacy and safety of NBP with a continuous dose regimen among patients with acute ischemic stroke. Methods A randomized, double-blind, double-dummy trial enrolled 573 patients within 48 hours of onset of ischemic stroke in China. Patients were randomly assigned to receive a 14-day infusion of NBP followed by an NBP capsule, a 14- day infusion of NBP followed by aspirin, or a 14-day infusion of ozagrel followed by aspirin. The efficacy measures were Barthel index score and the modified Rankin scale （mRS） at day 90. Differences among the three groups on mRS were compared using X2 test of proportions （with two-sided e=0.05） and Logistic regression analysis was conducted to take the baseline National Institutes of Health Stroke Scale （NIHSS） score into consideration. Results Among the 535 subjects included in the efficacy analysis, 90-day treatment with NBP was associated with a significantly favorable outcome than 14-day treatment with ozagrel as measured by mRS （P 〈0.001）. No significant difference was found among the three groups on Barthel index at day 90. The rate of adverse events was similar among the three groups. Conclusions The 90-day treatment with NBP could improve outcomes at the third month after stroke. The NBP treatment （both intravenous and oral） is safe （ChiCTR-TRC-09000483）.展开更多
Echinococcosis or hydatid disease （HD） is a zoonosis caused by the larval stages of taeniid cestodes belong- ing to the genus Echinococcus. Hepatic echinococcosis is a life-threatening disease, mainly differentiated...Echinococcosis or hydatid disease （HD） is a zoonosis caused by the larval stages of taeniid cestodes belong- ing to the genus Echinococcus. Hepatic echinococcosis is a life-threatening disease, mainly differentiated into alveolar and cystic forms, associated with Echinoc- cus multilocularis （E. multi/ocular/s） and Echinococcus granulosus （E. granulosus） infection, respectively. Cys- tic echinococcosis （CE） has a worldwide distribution, while hepatic alveolar echinococcosis （AE） is endemic in the Northern hemisphere, including North America and several Asian and European countries, like France, Germany and Austria. E. granulosus young cysts are spherical, unilocular vesicles, consisting of an internal germinal layer and an outer acellular layer. Cyst expansion is associated with a host immune reaction and the subsequent development of a fibrous layer, called the per/cyst; old cysts typically present internal septa- tions and daughter cysts. E. multilocularis has a tumor-like, infiltrative behavior, which is responsible for tissue destruction and finally for liver failure. The liver is the main site of HD involvement, for both alveolar and cystic hydatidosis. HD is usually asymptomatic for a long period of time, because cyst growth is commonly slow; the most frequent symptoms are fatigue and abdominal pain. Patients may also present jaundice, hepatomegaly or anaphylaxis, due to cyst leakage or rupture. HD diagnosis is usually accomplished with the combined use of ultrasonography and immunodiagnosis; furthermore, the improvement of surgical techniques, the introduction of minimally invasive treatments [such as puncture, aspiration, injection, re-aspiration （PAIR）] and more effective drugs （such as benzoimidazoles） have deeply changed life expectancy and quality of life of patients with HD. The aim of this article is to provide an up-to-date review of biological, diagnostic, clinical and therapeutic aspects of hepatic echinococcosis.展开更多
Increased microvessel density in the peri-infarct region has been reported and has been correlated with longer survival times in ischemic stroke patients and has improved outcomes in ischemic animal models.This raises...Increased microvessel density in the peri-infarct region has been reported and has been correlated with longer survival times in ischemic stroke patients and has improved outcomes in ischemic animal models.This raises the possibility that enhancement of angiogenesis is one of the strategies to facilitate functional recovery after ischemic stroke.Blood vessels and neuronal cells communicate with each other using various mediators and contribute to the pathophysiology of cerebral ischemia as a unit.In this mini-review,we discuss how angiogenesis might couple with axonal outgrowth/neurogenesis and work for functional recovery after cerebral ischemia.Angiogenesis occurs within 4 to 7 days after cerebral ischemia in the border of the ischemic core and periphery.Post-ischemic angiogenesis may contribute to neuronal remodeling in at least two ways and is thought to contribute to functional recovery.First,new blood vessels that are formed after ischemia are thought to have a role in the guidance of sprouting axons by vascular endothelial growth factor and laminin/β1-integrin signaling.Second,blood vessels are thought to enhance neurogenesis in three stages:1)Blood vessels enhance proliferation of neural stem/progenitor cells by expression of several extracellular signals,2)microvessels support the migration of neural stem/progenitor cells toward the peri-infarct region by supplying oxygen,nutrients,and soluble factors as well as serving as a scaffold for migration,and 3)oxygenation induced by angiogenesis in the ischemic core is thought to facilitate the differentiation of migrated neural stem/progenitor cells into mature neurons.Thus,the regions of angiogenesis and surrounding tissue may be coupled,representing novel treatment targets.展开更多
引言血管性认知损害（vascular cognitive impairment,VCI）诊断共识的缺乏（体现为多种不同评估方案的使用）,妨碍了对其理解和治疗的推进.多个国家的大量临床医生和研究人员参与了2个阶段血管性认知损害分类共识研究（Vascular Impair...引言血管性认知损害（vascular cognitive impairment,VCI）诊断共识的缺乏（体现为多种不同评估方案的使用）,妨碍了对其理解和治疗的推进.多个国家的大量临床医生和研究人员参与了2个阶段血管性认知损害分类共识研究（Vascular Impairment of Cognition Classification Consensus Study,VICCCS）,旨在就VCI的诊断原则（VICCCS-1）和诊断方案（VICCCS-2）达成一致意见.本文提供了VICCCS-2的相关内容.方法使用VICCCS-1达成的原则和已发表的诊断指南作为在线德尔菲（Delphi）调查的参考基点,以期对VCI的临床诊断达成共识.结果共进行了6轮调查,每轮有65～79名专家参与,他们就VICCCS修订的轻度和重度VCI的诊断指南达成共识,并肯定了美国国立神经疾病与卒中研究所-加拿大卒中网（National Institute of Neurological Disorders and Stroke–Canadian Stroke Network,NINDS-CSN）发布的神经心理学评估方案和对影像学检查的推荐意见.讨论VICCCS-2建议规范化应用NINDS-CSN推荐的神经心理学和影像学评估方案诊断VCI,以促进研究协作.展开更多
Background and purpose Stroke is the leading cause of mortality and disability in China.Precise aetiological classification,imaging and biological markers may predict the prognosis of stroke.The Third China National S...Background and purpose Stroke is the leading cause of mortality and disability in China.Precise aetiological classification,imaging and biological markers may predict the prognosis of stroke.The Third China National Stroke Registry(CNSR-Ⅲ),a nationwide registry of ischaemic stroke or transient ischaemic attack(TIA)in China based on aetiology,imaging and biology markers,will be considered to clarify the pathogenesis and prognostic factors of ischaemic stroke.Methods Between August 2015 and March 2018,the CNSR-Ⅲrecruited consecutive patients with ischaemic stroke or TIA from 201 hospitals that cover 22 provinces and four municipalities in China.Clinical data were collected prospectively using an electronic data capture system by face-to-face interviews.Patients were followed for clinical outcomes at 3 months,6 months and 1-5 year annually.Brain imaging,including brain MRI and CT,were completed at baseline.Blood samples were collected and biomarkers were tested at baseline.Results A total of 15166 stroke patients were enrolled,among which 31.7%patients were women with the average age of 62.2±11.3 years.Ischaemic stroke was predominant(93.3%,n=14146)and 1020(6.7%)TIAs were enrolled.Conclusions CNSR-Ⅲis a large scale nationwide registry in China.Data from this prospective registry may provide opportunity to evaluate imaging and biomarker prognostic determinants of stroke.展开更多
INTRODUCTIONDiscovery of the spectrum ofautoimmune encephalitis （ALE） is among the most attractive events of neurology in the past decade. AIE includes a heterogeneous group of encephalitic syndromes, which generall...INTRODUCTIONDiscovery of the spectrum ofautoimmune encephalitis （ALE） is among the most attractive events of neurology in the past decade. AIE includes a heterogeneous group of encephalitic syndromes, which generally include two major categories： classic paraneoplastic limbic encephalitis （LE） associated with the so-called well-characterized onconeural autoantibodies against intracellular neuronal antigens （e.g., Hu, Ma2, etc.） and new-type AIE associated with autoantibodies to the neuronal surface or synaptic antigens.展开更多
Background Edaravone Dexborneol is a novel neuroprotective agent that comprised edaravone and(+)-borneol,a food additive with an anti-inflammatory effect in animal ischaemic stroke models.This study aims to assess the...Background Edaravone Dexborneol is a novel neuroprotective agent that comprised edaravone and(+)-borneol,a food additive with an anti-inflammatory effect in animal ischaemic stroke models.This study aims to assess the safety and efficacy of Edaravone Dexborneol compared with edaravone in treating patients with acute ischaemic stroke(AIS).Methods In this multicentre,randomised,double-blind,multiple-dose,active-controlled,phaseⅡclinical trial,patients with AIS within 48 hours after stroke onset were randomly assigned(1:1:1:1)to low-dose(12.5 mg),medium-dose(37.5 mg)or high-dose(62.5 mg)Edaravone Dexborneol groups,and an active control group with edaravone(30 mg)by 30 min intravenous infusion every 12 hours,for 14 consecutive days.The primary efficacy outcome was the proportion of modified Rankin Scale(mRS)score≤1 at 90 days and National Institutes of Health Stroke Scale(NIHSS)score change from baseline to 14 days after randomisation.The safety outcome included any adverse event during 90 days after treatment.Results Of 385 patients included in the efficacy analysis,94 were randomised to low-dose group,97 to medium-dose group,98 to high-dose group and 96 to the control group.No significant difference was observed among the four groups on mRS score(mRS≤1,p=0.4054)at 90 days or NIHSS score change at 14 days(p=0.6799).However,a numerically higher percentage of patients with mRSscore≤1 at 90 days in the medium-dose(69.39%)and high-dose(65.63%)groups was observed than in the control group(60.64%).No significant difference in severe adverse events was found among the four groups(p=0.3815).Conclusions Compared with edaravone alone,Edaravone Dexborneol was safe and well tolerated at all doses,although no significant improvement in functional outcomes was observed at 90days.展开更多
基金This study was funded by Ministry of Science and Technology of the People’s Republic of China,National Key R&D Programme of China(2017YFC1310901,2016YFC0901002,2017YFC1307905,and 2015BAI12B00)the Youth Programme(QML20180501)+1 种基金National Natural Science Foundation of China(81801152)Beijing Talents Project(2018000021223ZK03 and 2018A13).
文摘China faces the greatest challenge from stroke in the world.The death rate for cerebrovascular diseases in China was 149.49 per 100000,accounting for 1.57 million deaths in 2018.It ranked third among the leading causes of death behind malignant tumours and heart disease.The age-standardised prevalence and incidence of stroke in 2013 were 1114.8 per 100000 population and 246.8 per 100000 person-years,respectively.According to the Global Burden of Disease Study 2017,the years of life lost(YLLs)per 100000 population for stroke increased by 14.6%;YLLs due to stroke rose from third highest among all causes in 1990 to the highest in 2017.The absolute numbers and rates per 100000 population for all-age disability-adjusted life years(DALYs)for stroke increased substantially between 1990 and 2017,and stroke was the leading cause of all-age DALYs in 2017.The main contributors to cerebrovascular diseases include behavioural risk factors(smoking and alcohol use)and pre-existing conditions(hypertension,diabetes mellitus,dyslipidaemia and atrial fibrillation(AF)).The most prevalent risk factors among stroke survivors were hypertension(63.0%-84.2%)and smoking(31.7%-47.6%).The least prevalent was AF(2.7%-7.4%).The prevalences for major risk factors for stroke are high and most have increased over time.Based on the latest national epidemiological data,26.6%of adults aged≥15 years(307.6 million adults)smoked tobacco products.For those aged≥18 years,age-adjusted prevalence of hypertension was 25.2%;adjusted prevalence of hypercholesterolaemia was 5.8%;and the standardised prevalence of diabetes was 10.9%.For those aged≥40 years,the standardised prevalence of AF was 2.31%.Data from the Hospital Quality Monitoring System showed that 3010204 inpatients with stroke were admitted to 1853 tertiary care hospitals during 2018.Of those,2466785(81.9%)were ischaemic strokes(ISs);447609(14.9%)were intracerebral haemorrhages(ICHs);and 95810(3.2%)were subarachnoid haemorrhages(SAHs).The average age of patients admitted was 66 years old,and
基金supported by the National Health Commission of the People’s Republic of China (201302002,Clinical Trial NCT02200679)。
文摘This study aimed to obtain the first national estimate of the prevalence of autism spectrum disorder(ASD) in Chinese children.We targeted the population of 6 to 12-year-old children for this prevalence study by multistage convenient cluster sampling.The Modified Chinese Autism Spectrum Rating Scale was used for the screening process.Of the target population of 142,086 children,88.5%(n=125,806) participated in the study.A total of 363 children were confirmed as having ASD.The observed ASD prevalence rate was 0.29%(95% CI:0.26%-0.32%) for the overall population.After adjustment for response rates,the estimated number of ASD cases was867 in the target population sample,thereby achieving an estimated prevalence of 0.70%(95% CI:0.64%-0.74%).The prevalence was significantly higher in boys than in girls(0.95%;95% CI:0.87%-1.02% versus 0.30%;95%CI:0.26%-0.34%;P <0.001).Of the 363 confirmed ASD cases,43.3% were newly diagnosed,and most of those(90.4%) were attending regular schools,and 68.8% of the children with ASD had at least one neuropsychiatric comorbidity.Our findings provide reliable data on the estimated ASD prevalence and comorbidities in Chinese children.
基金This work was supported by the Fundamental Research Funds for the Central Universities(WK2070000191,WK9110000037)the fellowship of China National Postdoctoral Program for Innovative Talents(BX20200325)the Natural Science Foundation of Anhui province(1808085QH244).
文摘The NLRP3 inflammasome is a cytosolic multiprotein complex composed of the innate immune receptor protein NLRP3,adapter protein ASC,and inflammatory protease caspase-1 that responds to microbial infection,endogenous danger signals,and environmental stimuli.The assembled NLRP3 inflammasome can activate the protease caspase‐1 to induce gasdermin D-dependent pyroptosis and facilitate the release of IL-1β and IL-18,which contribute to innate immune defense and homeostatic maintenance.However,aberrant activation of the NLRP3 inflammasome is associated with the pathogenesis of various inflammatory diseases,such as diabetes,cancer,and Alzheimer’s disease.Recent studies have revealed that NLRP3 inflammasome activation contributes to not only pyroptosis but also other types of cell death,including apoptosis,necroptosis,and ferroptosis.In addition,various effectors of cell death have been reported to regulate NLRP3 inflammasome activation,suggesting that cell death is closely related to NLRP3 inflammasome activation.In this review,we summarize the inextricable link between NLRP3 inflammasome activation and cell death and discuss potential therapeutics that target cell death effectors in NLRP3 inflammasome-associated diseases.
基金supported by grants by NIH grant AR-044741(Y-PL) and R01DE023813 (Y-PL)
文摘INTRODUCTIONThe transforming growth factor-β （TGF-β） superfamily com- prises TGF-βs, Activin, bone morphogenetic proteins （BMPs） and other related proteins. TGF-β superfamily members act through a heteromeric receptor complex,, comprised of type I and type II receptors at the cell surface that transduce intracellular signals via Smad complex or mitogen-activated protein kinase （MAPK） cascade.
基金supported by the Natural Science Foundation of Shanghai of China,No.17ZR1425800(to KYL)the Shanghai Pudong District Health Bureau of China,No.PDZX2017-25(to KYL)
文摘Appropriate autophagy has protective effects on ischemic nerve tissue,while excessive autophagy may cause cell death.The inflammatory response plays an important role in the survival of nerve cells and the recovery of neural tissue after ischemia.Many studies have found an interaction between autophagy and inflammation in the pathogenesis of ischemic stroke.This study outlines recent advances regarding the role of autophagy in the post-stroke inflammatory response as follows.(1)Autophagy inhibits inflammatory responses caused by ischemic stimulation through mTOR,the AMPK pathway,and inhibition of inflammasome activation.(2)Activation of inflammation triggers the formation of autophagosomes,and the upregulation of autophagy levels is marked by a significant increase in the autophagy-forming markers LC3-II and Beclin-1.Lipopolysaccharide stimulates microglia and inhibits ULK1 activity by direct phosphorylation of p38 MAPK,reducing the flux and autophagy level,thereby inducing inflammatory activity.(3)By blocking the activation of autophagy,the activation of inflammasomes can alleviate cerebral ischemic injury.Autophagy can also regulate the phenotypic alternation of microglia through the nuclear factor-κB pathway,which is beneficial to the recovery of neural tissue after ischemia.Studies have shown that some drugs such as resveratrol can exert neuroprotective effects by regulating the autophagy-inflammatory pathway.These studies suggest that the autophagy-inflammatory pathway may provide a new direction for the treatment of ischemic stroke.
文摘Artificial intelligence(AI)aims to mimic human cognitive functions.It is bringing a paradigm shift to healthcare,powered by increasing availability of healthcare data and rapid progress of analytics techniques.We survey the current status of AI applications in healthcare and discuss its future.AI can be applied to various types of healthcare data(structured and unstructured).Popular AI techniques include machine learning methods for structured data,such as the classical support vector machine and neural network,and the modern deep learning,as well as natural language processing for unstructured data.Major disease areas that use AI tools include cancer,neurology and cardiology.We then review in more details the AI applications in stroke,in the three major areas of early detection and diagnosis,treatment,as well as outcome prediction and prognosis evaluation.We conclude with discussion about pioneer AI systems,such as IBM Watson,and hurdles for real-life deployment of AI.
基金YS is supported by the China Scholarships Council.The work described in this paper was supported by the Wellcome Trust(WT088134/Z/09/A)the MRC,the Scottish Chief Scientist Office(CZB/4/281)Chest Heart Stroke Scotland,the UK HTA,etc.
文摘Cerebral small vessel disease(CSVD)is a very common neurological disease in older people.It causes stroke and dementia,mood disturbance and gait problems.Since it is difficult to visualise CSVD pathologies in vivo,the diagnosis of CSVD has relied on imaging findings including white matter hyperintensities,lacunar ischaemic stroke,lacunes,microbleeds,visible perivascular spaces and many haemorrhagic strokes.However,variations in the use of definition and terms of these features have probably caused confusion and difficulties in interpreting results of previous studies.A standardised use of terms should be encouraged in CSVD research.These CSVD features have long been regarded as different lesions,but emerging evidence has indicated that they might share some common intrinsic microvascular pathologies and therefore,owing to its diffuse nature,CSVD should be regarded as a‘whole-brain disease’.Single antiplatelet(for acute lacunar ischaemic stroke)and management of traditional risk factors still remain the most important therapeutic and preventive approach,due to limited understanding of pathophysiology in CSVD.Increasing evidence suggests that new studies should consider drugs that target endothelium and blood–brain barrier to prevent and treat CSVD.Epidemiology of CSVD might differ in Asian compared with Western populations(where most results and guidelines about CSVD and stroke originate),but more community-based data and clear stratification of stroke types are required to address this.
基金the National Natural Science Foundation of China (81571132, 81873743, and 81801223)Fundamental Research Funds for the Central Universities, China (2017KFYXJJ107 and 2017KFYXJJ124)the National Institutes of Health, USA (R01NS088627)
文摘Ischemic stroke is a leading cause of morbidity and mortality worldwide. Resident microglia are the principal immune cells of the brain, and the first to respond to the pathophysiological changes induced by ischemic stroke. Traditionally, it has been thought that microglial activation is deleterious in ischemic stroke, and therapies to suppress it have been intensively explored. However,increasing evidence suggests that microglial activation is also critical for neurogenesis, angiogenesis, and synaptic remodeling, thereby promoting functional recovery after cerebral ischemia. Here, we comprehensively review the dual role of microglia during the different phases of ischemic stroke, and the possible mechanisms controlling the post-ischemic activity of microglia. In addition, we discuss the dynamic interactions between microglia and other cells, such as neurons, astrocytes, oligodendrocytes,and endothelial cells within the brain parenchyma and the neurovascular unit.
基金supported by National Basic Research Development Program(973 Program)of China(2011CBA00400)the National Natural Science Foundation of China(91332201)+1 种基金the Natural Science Foundation of Shanghai Municipality,China(13JC1401500)fund for Medical Emerging Cutting-edge Technology in Shanghai Municipality,China(SHDC12012114)
文摘Oxidative stress plays a significant role in the pathogenesis of Alzheimer＇s disease （AD）, a devastating disease of the elderly. The brain is more vulnerable than other organs to oxidative stress, and most of the components of neurons （lipids, proteins, and nucleic acids） can be oxidized in AD due to mitochondrial dysfunction, increased metal levels, inflammation, and β-amyloid （Aβ） peptides. Oxidative stress participates in the development of AD by promoting Aβ deposition, tau hyperphosphorylation, and the subsequent loss of synapses and neurons. The relationship between oxidative stress and AD suggests that oxidative stress is an essential part of the pathological process, and antioxidants may be useful for AD treatment.
基金supported by the Basic Science Research Program of the National Research Foundation of Korea,which was funded by the Ministry of Science,ICT,and Future Planning(2018R1A2A2A15023219)a grant of the Korea Health Technology R&D Projea through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(HI20C0253)the Medical Research Centre(2017R1A5A2015395).
文摘Neuroinflammation is associated with neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease,ancamyotrophic lateral sclerosis.Microglia and astrocytes are key regulators of inflammatory responses in the central nervous system.The activation of microglia and astrocytes is heterogeneous and traditionally categorized as neurotoxi(M1-phenotype microglia and A1-phenotype astrocytes)or neuroprotective(M2-phenotype microglia and A2-phenotype astrocytes).However,this dichotomized classification may not reflect the various phenotypes of microgliaand astrocytes.The relationship between these activated glial cells is also very complicated,and the phenotypic distribution can change,based on the progression of neurodegenerative diseases.A better understanding of the rolesof microglia and astrocytes in neurodegenerative diseases is essential for developing effective therapies.In this review,we discuss the roles of inflammatory response in neurodegenerative diseases,focusing on the contributions of microglia and astrocytes and their relationship.In addition,we discuss biomarkers to measure neuroinflammation andstudies on therapeutic drugs that can modulate neuroinflammation.
基金This study was supported by grants from Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support （No. XMLX201401）, the National Natural Science Foundation of China （No. 81301138）, National High-Tech R＆D Program of China （863 Program, No. 2015AA020514）, National Hundred, Thousand, and Ten Thousand Talents Project of Beijing （No. 2010-005）.
文摘Objective：To systematically review the updated information about the gut microbiota-brain axis.Data Sources：All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literature search on PubMed,ScienceDirect,and Web of Science,with the keywords of＂gut microbiota＂,＂gut-brain axis＂,and ＂neuroscience＂.Study Selection：All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed,with no limitation of study design.Results：It is well-recognized that gut microbiota affects the brain＆#39;s physiological,behavioral,and cognitive functions although its precise mechanism has not yet been fully understood.Gut microbiota-brain axis may include gut microbiota and their metabolic products,enteric nervous system,sympathetic and parasympathetic branches within the autonomic nervous system,neural-immune system,neuroendocrine system,and central nervous system.Moreover,there may be five communication routes between gut microbiota and brain,including the gut-brain＆#39;s neural network,neuroendocrine-hypothalamic-pituitary-adrenal axis,gut immune system,some neurotransmitters and neural regulators synthesized by gut bacteria,and barrier paths including intestinal mucosal barrier and blood-brain barrier.The microbiome is used to define the composition and functional characteristics of gut microbiota,and metagenomics is an appropriate technique to characterize gut microbiota.Conclusions：Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain,which may provide a new way to protect the brain in the near future.
文摘Background DI-3-n-butylphthalide （NBP）, first isolated from the seeds of celery, showed efficacy in animal models of stroke. This study was a clinical trial to assess the efficacy and safety of NBP with a continuous dose regimen among patients with acute ischemic stroke. Methods A randomized, double-blind, double-dummy trial enrolled 573 patients within 48 hours of onset of ischemic stroke in China. Patients were randomly assigned to receive a 14-day infusion of NBP followed by an NBP capsule, a 14- day infusion of NBP followed by aspirin, or a 14-day infusion of ozagrel followed by aspirin. The efficacy measures were Barthel index score and the modified Rankin scale （mRS） at day 90. Differences among the three groups on mRS were compared using X2 test of proportions （with two-sided e=0.05） and Logistic regression analysis was conducted to take the baseline National Institutes of Health Stroke Scale （NIHSS） score into consideration. Results Among the 535 subjects included in the efficacy analysis, 90-day treatment with NBP was associated with a significantly favorable outcome than 14-day treatment with ozagrel as measured by mRS （P 〈0.001）. No significant difference was found among the three groups on Barthel index at day 90. The rate of adverse events was similar among the three groups. Conclusions The 90-day treatment with NBP could improve outcomes at the third month after stroke. The NBP treatment （both intravenous and oral） is safe （ChiCTR-TRC-09000483）.
文摘Echinococcosis or hydatid disease （HD） is a zoonosis caused by the larval stages of taeniid cestodes belong- ing to the genus Echinococcus. Hepatic echinococcosis is a life-threatening disease, mainly differentiated into alveolar and cystic forms, associated with Echinoc- cus multilocularis （E. multi/ocular/s） and Echinococcus granulosus （E. granulosus） infection, respectively. Cys- tic echinococcosis （CE） has a worldwide distribution, while hepatic alveolar echinococcosis （AE） is endemic in the Northern hemisphere, including North America and several Asian and European countries, like France, Germany and Austria. E. granulosus young cysts are spherical, unilocular vesicles, consisting of an internal germinal layer and an outer acellular layer. Cyst expansion is associated with a host immune reaction and the subsequent development of a fibrous layer, called the per/cyst; old cysts typically present internal septa- tions and daughter cysts. E. multilocularis has a tumor-like, infiltrative behavior, which is responsible for tissue destruction and finally for liver failure. The liver is the main site of HD involvement, for both alveolar and cystic hydatidosis. HD is usually asymptomatic for a long period of time, because cyst growth is commonly slow; the most frequent symptoms are fatigue and abdominal pain. Patients may also present jaundice, hepatomegaly or anaphylaxis, due to cyst leakage or rupture. HD diagnosis is usually accomplished with the combined use of ultrasonography and immunodiagnosis; furthermore, the improvement of surgical techniques, the introduction of minimally invasive treatments [such as puncture, aspiration, injection, re-aspiration （PAIR）] and more effective drugs （such as benzoimidazoles） have deeply changed life expectancy and quality of life of patients with HD. The aim of this article is to provide an up-to-date review of biological, diagnostic, clinical and therapeutic aspects of hepatic echinococcosis.
基金supported by a Grant-in-Aid for Scientific Research(Research Project No.15K19478 and 18K07493,both to MK)Japan Science and Technology Agency(JST),the Translational Research program+7 种基金Strategic Promotion for practical application of Innovative medical Technology(TR-SPRINT)supported by Japan Agency for Medical Research and Development(AMED)under Grant No.JP19lm0203023a grant from Takeda Science Foundationthe Bayer Scholarship for Cardiovascular ResearchJapan Cardiovascular Research FoundationAstellas Foundation for Research on Metabolic DisordersYoung Investigator Okamoto AwardMedical Research Encouragement Prize of the Japan Medical Association(to MK)supported by a grant from Tsubaki Memorial Foundation(to MH and IN)
文摘Increased microvessel density in the peri-infarct region has been reported and has been correlated with longer survival times in ischemic stroke patients and has improved outcomes in ischemic animal models.This raises the possibility that enhancement of angiogenesis is one of the strategies to facilitate functional recovery after ischemic stroke.Blood vessels and neuronal cells communicate with each other using various mediators and contribute to the pathophysiology of cerebral ischemia as a unit.In this mini-review,we discuss how angiogenesis might couple with axonal outgrowth/neurogenesis and work for functional recovery after cerebral ischemia.Angiogenesis occurs within 4 to 7 days after cerebral ischemia in the border of the ischemic core and periphery.Post-ischemic angiogenesis may contribute to neuronal remodeling in at least two ways and is thought to contribute to functional recovery.First,new blood vessels that are formed after ischemia are thought to have a role in the guidance of sprouting axons by vascular endothelial growth factor and laminin/β1-integrin signaling.Second,blood vessels are thought to enhance neurogenesis in three stages:1)Blood vessels enhance proliferation of neural stem/progenitor cells by expression of several extracellular signals,2)microvessels support the migration of neural stem/progenitor cells toward the peri-infarct region by supplying oxygen,nutrients,and soluble factors as well as serving as a scaffold for migration,and 3)oxygenation induced by angiogenesis in the ischemic core is thought to facilitate the differentiation of migrated neural stem/progenitor cells into mature neurons.Thus,the regions of angiogenesis and surrounding tissue may be coupled,representing novel treatment targets.
文摘引言血管性认知损害（vascular cognitive impairment,VCI）诊断共识的缺乏（体现为多种不同评估方案的使用）,妨碍了对其理解和治疗的推进.多个国家的大量临床医生和研究人员参与了2个阶段血管性认知损害分类共识研究（Vascular Impairment of Cognition Classification Consensus Study,VICCCS）,旨在就VCI的诊断原则（VICCCS-1）和诊断方案（VICCCS-2）达成一致意见.本文提供了VICCCS-2的相关内容.方法使用VICCCS-1达成的原则和已发表的诊断指南作为在线德尔菲（Delphi）调查的参考基点,以期对VCI的临床诊断达成共识.结果共进行了6轮调查,每轮有65～79名专家参与,他们就VICCCS修订的轻度和重度VCI的诊断指南达成共识,并肯定了美国国立神经疾病与卒中研究所-加拿大卒中网（National Institute of Neurological Disorders and Stroke–Canadian Stroke Network,NINDS-CSN）发布的神经心理学评估方案和对影像学检查的推荐意见.讨论VICCCS-2建议规范化应用NINDS-CSN推荐的神经心理学和影像学评估方案诊断VCI,以促进研究协作.
基金This study was supported by grants from the Ministry of Science and Technology of the People’s Republic of China(2016YFC0901001,2016YFC0901002,2017YFC1310901,2017YFC1310902,2018YFC1311700 and 2018YFC1311706)grants from Beijing Municipal Commission of Health and Family Planning(No.2016-1-2041,SML20150502).
文摘Background and purpose Stroke is the leading cause of mortality and disability in China.Precise aetiological classification,imaging and biological markers may predict the prognosis of stroke.The Third China National Stroke Registry(CNSR-Ⅲ),a nationwide registry of ischaemic stroke or transient ischaemic attack(TIA)in China based on aetiology,imaging and biology markers,will be considered to clarify the pathogenesis and prognostic factors of ischaemic stroke.Methods Between August 2015 and March 2018,the CNSR-Ⅲrecruited consecutive patients with ischaemic stroke or TIA from 201 hospitals that cover 22 provinces and four municipalities in China.Clinical data were collected prospectively using an electronic data capture system by face-to-face interviews.Patients were followed for clinical outcomes at 3 months,6 months and 1-5 year annually.Brain imaging,including brain MRI and CT,were completed at baseline.Blood samples were collected and biomarkers were tested at baseline.Results A total of 15166 stroke patients were enrolled,among which 31.7%patients were women with the average age of 62.2±11.3 years.Ischaemic stroke was predominant(93.3%,n=14146)and 1020(6.7%)TIAs were enrolled.Conclusions CNSR-Ⅲis a large scale nationwide registry in China.Data from this prospective registry may provide opportunity to evaluate imaging and biomarker prognostic determinants of stroke.
文摘INTRODUCTIONDiscovery of the spectrum ofautoimmune encephalitis （ALE） is among the most attractive events of neurology in the past decade. AIE includes a heterogeneous group of encephalitic syndromes, which generally include two major categories： classic paraneoplastic limbic encephalitis （LE） associated with the so-called well-characterized onconeural autoantibodies against intracellular neuronal antigens （e.g., Hu, Ma2, etc.） and new-type AIE associated with autoantibodies to the neuronal surface or synaptic antigens.
基金Simcere Pharmaceutical Group supported the present study
文摘Background Edaravone Dexborneol is a novel neuroprotective agent that comprised edaravone and(+)-borneol,a food additive with an anti-inflammatory effect in animal ischaemic stroke models.This study aims to assess the safety and efficacy of Edaravone Dexborneol compared with edaravone in treating patients with acute ischaemic stroke(AIS).Methods In this multicentre,randomised,double-blind,multiple-dose,active-controlled,phaseⅡclinical trial,patients with AIS within 48 hours after stroke onset were randomly assigned(1:1:1:1)to low-dose(12.5 mg),medium-dose(37.5 mg)or high-dose(62.5 mg)Edaravone Dexborneol groups,and an active control group with edaravone(30 mg)by 30 min intravenous infusion every 12 hours,for 14 consecutive days.The primary efficacy outcome was the proportion of modified Rankin Scale(mRS)score≤1 at 90 days and National Institutes of Health Stroke Scale(NIHSS)score change from baseline to 14 days after randomisation.The safety outcome included any adverse event during 90 days after treatment.Results Of 385 patients included in the efficacy analysis,94 were randomised to low-dose group,97 to medium-dose group,98 to high-dose group and 96 to the control group.No significant difference was observed among the four groups on mRS score(mRS≤1,p=0.4054)at 90 days or NIHSS score change at 14 days(p=0.6799).However,a numerically higher percentage of patients with mRSscore≤1 at 90 days in the medium-dose(69.39%)and high-dose(65.63%)groups was observed than in the control group(60.64%).No significant difference in severe adverse events was found among the four groups(p=0.3815).Conclusions Compared with edaravone alone,Edaravone Dexborneol was safe and well tolerated at all doses,although no significant improvement in functional outcomes was observed at 90days.
