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
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
One of the most important points in the meta-analyses is certainly represented by the assessment of the quality of the studies included in such research. The meta-analyses are considered the highest level of evidence ...One of the most important points in the meta-analyses is certainly represented by the assessment of the quality of the studies included in such research. The meta-analyses are considered the highest level of evidence in science. Also for this reason, the quality of the studies included should be accurately evaluated by standardized tools. The overall results of the metaanalysis depend indeed also on a rigorous evaluation of the studies quality. Among all the possible tools for this complex evaluation, the Newcastle Ottawa Scale(NOS) is one of the most used worldwide, above all for observational studies. In this review, we will discuss the strengths and limitation of the NOS, also on the basis of the branch of science in which it has been applied.展开更多
INTRODUCTION Sleep disturbance is one of the most common nonmotor symptoms in Parkinson's disease (PD).Sleep disturbance affects 40-98% of PD patients in the world. In China, the prevalence of PD patients with sle...INTRODUCTION Sleep disturbance is one of the most common nonmotor symptoms in Parkinson's disease (PD).Sleep disturbance affects 40-98% of PD patients in the world. In China, the prevalence of PD patients with sleep disturbance ranges from 47.66% to 89.10%. Sleep disturbance usually has adverse impact on the quality of life of PD patients. Apossible pathogenesis of PD with sleep disturbance include thalamocortical pathway degeneration and changes of neurotransmitter systems. The etiology of sleep disturbance is multifactorial,involving degeneration of areas regulating sleep,sleep structure affected by drugs,sleep disturbance induced by drug,and sleep fragmentation by multiple factors.展开更多
Objective:Neutrophil extracellular traps(NETs)produced by tumor-infiltrating neutrophils(TINs)are associated with poor prognosis in patients with several types of cancer.However,the mechanisms underlying the involveme...Objective:Neutrophil extracellular traps(NETs)produced by tumor-infiltrating neutrophils(TINs)are associated with poor prognosis in patients with several types of cancer.However,the mechanisms underlying the involvement of NETs in glioma progression remain largely unknown.This study aimed to elucidate the roles of NETs in biological processes that drive the crosstalk between glioma progression and the tumor microenvironment.Methods:Neutrophil infiltration and NETs formation were investigated in glioma tissue through immunohistochemistry,and their relationships with clinicopathological features and outcomes were statistically evaluated.The effects of NETs on glioma cell progression were studied in a co-culture system.In vivo and in vitro experiments validated the reactive oxygen species activity and cytokine production of TINs,as well as the ERK signaling pathway activation and the metastasis of gliomas.Results:Neutrophil infiltration and NETs formation were induced in high-grade glioma compared with low-grade glioma.NETs induced by TINs were determined to be an oncogenic marker of high-grade gliomas and to be involved in cell proliferation and invasion.NETs overproduction promoted glioma cell proliferation,migration,and invasion.Furthermore,HMGB1 was found to bind to RAGE and activate the NF-κB signaling pathway in vitro.In addition,NETs stimulated the NF-κB signaling pathway,thus promoting IL-8 secretion in glioblastoma.Subsequently,IL-8 recruited neutrophils which in turn mediated NETs formation via the PI3 K/AKT/ROS axis in TINs.Conclusions:Our results suggest that NETs produced by TINs mediate the crosstalk between glioma progression and the tumor microenvironment by regulating the HMGB1/RAGE/IL-8 axis.Targeting NETs formation or IL-8 secretion may be an effective approach to inhibit glioma progression.展开更多
Abstract： With the rapid development of assisted reproductive technology, various reproductive disorders have been effectively addressed. Acupuncture-like therapies, including electroacupuncture （EA） and transcutan...Abstract： With the rapid development of assisted reproductive technology, various reproductive disorders have been effectively addressed. Acupuncture-like therapies, including electroacupuncture （EA） and transcutaneous electrical acupoint stimulation （TEAS）, become more popular world-wide. Increasing evidence has demonstrated that EA and TEAS are effective in treating gynecological disorders, especially infertility. This present paper describes how to select acupoints for the treatment of infertility from the view of theories of traditional Chinese medicine and how to determine critical parameters of electric pulses of ENTEAS based on results from animal and clinical studies. It summarizes the principles of clinical application of EA/rEAS in treating various kinds of reproductive disorders, such as polycystic ovary syndrome （PCOS）, pain induced by oocyte retrieval, diminished ovarian reserve, embryo transfer, and oligosperrnia/ asthenospermia. The possible underlying mechanisms mediating the therapeutic effects of EA/TEAS in reproductive medicine are also examined.展开更多
Gradual degeneration and loss of dopaminergic neurons in the substantia nigra,pars compacta and subsequent reduction of dopamine levels in striatum are associated with motor deficits that characterize Parkinson’s dis...Gradual degeneration and loss of dopaminergic neurons in the substantia nigra,pars compacta and subsequent reduction of dopamine levels in striatum are associated with motor deficits that characterize Parkinson’s disease(PD).In addition,half of the PD patients also exhibit frontostriatal-mediated executive dysfunction,including deficits in attention,short-term working memory,speed of mental processing,and impulsivity.The most commonly used treatments for PD are only partially or transiently effective and are available or applicable to a minority of patients.Because,these therapies neither restore the lost or degenerated dopaminergic neurons,nor prevent or delay the disease progression,the need for more effective therapeutics is critical.In this review,we provide a comprehensive overview of the current understanding of the molecular signaling pathways involved in PD,particularly within the context of how genetic and environmental factors contribute to the initiation and progression of this disease.The involvement of molecular chaperones,autophagy-lysosomal pathways,and proteasome systems in PD are also highlighted.In addition,emerging therapies,including pharmacological manipulations,surgical procedures,stem cell transplantation,gene therapy,as well as complementary,supportive and rehabilitation therapies to prevent or delay the progression of this complex disease are reviewed.展开更多
AIM: To assess the impact of percutaneous cardiac support in cardiogenic shock(CS) complicating acute myocardial infarction(AMI), treated with percutaneous coronary intervention. METHODS: We selected all of the studie...AIM: To assess the impact of percutaneous cardiac support in cardiogenic shock(CS) complicating acute myocardial infarction(AMI), treated with percutaneous coronary intervention. METHODS: We selected all of the studies published from January 1st, 1997 to May 15 st, 2015 that compared the following percutaneous mechanical support in patients with CS due to AMI undergoing myocardial revascularization:(1) intra-aortic balloon pump(IABP) vs Medical therapy;(2) percutaneous left ventricular assist devices(PLVADs) vs IABP;(3) complete extracorporeal life support with extracorporeal membrane oxygenation(ECMO) plus IABP vs IABP alone; and(4) ECMO plus IABP vs ECMO alone, in patients with AMI and CS undergoing myocardial revascularization. We evaluated the impact of the support devices on primary and secondary endpoints. Primary endpoint was the inhospital mortality due to any cause during the same hospital stay and secondary endpoint late mortality at 6-12 moof follow-up. RESULTS: One thousand two hundred and seventytwo studies met the initial screening criteria. After detailed review, only 30 were selected. There were 6 eligible randomized controlled trials and 24 eligible observational studies totaling 15799 patients. We found that the inhospital mortality was:(1) significantly higher with IABP support vs medical therapy(RR = +15%, P = 0.0002);(2) was higher, although not significantly, with PLVADs compared to IABP(RR = +14%, P = 0.21); and(3) significantly lower in patients treated with ECMO plus IABP vs IABP(RR =-44%, P = 0.0008) or ECMO(RR =-20%, P = 0.006) alone. In addition, Trial Sequential Analysis showed that in the comparison of IABP vs medical therapy, the sample size was adequate to demonstrate a significant increase in risk due to IABP. CONCLUSION: Inhospital mortality was significantly higher with IABP vs medical therapy. PLVADs did not reduce early mortality. ECMO plus IABP significantly reduced inhospital mortality compared to IABP.展开更多
Background The incidence of spinal injury with spinal cord contusion is high in developed countries and is now growing in China. Furthermore, spinal cord injury happens mostly in young people who have a long life expe...Background The incidence of spinal injury with spinal cord contusion is high in developed countries and is now growing in China. Furthermore, spinal cord injury happens mostly in young people who have a long life expectance. A large number of patients thus are wheelchair bound for the rest of their lives. Therefore, spinal cord injury has aroused great concern worldwide. Despite great efforts, recovery from spinal cord injury remains unsatisfactory. Based on the pathology of spinal cord contusion, an idea of early neurosurgical intervention has been formulated in this study. Methods A total of 30 patients with ＂complete＂ spinal cord injury or classified as American Spinal Injury Association （ASIA）-A were studied. Orthopedic treatment of the injured vertebra（e）, internal fixation of the vertebral column, and bilateral laminectomy for epidural decompression were followed directly by neurosurgical management, including separation of the arachnoid adhesion to restore cerebrospinal fluid flow and debridement of the spinal cord necrotic tissue with concomitant intramedullary decompression. Rehabilitation started 17 days after the operation. The final outcome was evaluated after 3 months of rehabilitation. Pearson chi-square analysis was used for statistical analysis. Results All the patients recovered some ability to walk. The least recovered patients were able to walk with a wheeled weight support and help in stabilizing the weight bearing knee joint （12 cases, 40%）. Thirteen patients （43%） were able to walk with a pair of crutches, a stick or without any support. The timing of the operation after injury was important. An optimal operation time window was identified at 4-14 days after injury. Conclusions Early neurosurgical intervention of spinal cord contusion followed by rehabilitation can significantly improve the locomotion of the patients. It is a new idea of a therapeutic approach for spinal cord contusion and has been proven to be very successful.展开更多
Objective：To review recent research advances on tau,a major player in Alzheimer＇s disease （AD） pathogenesis,a biomarker for AD onset,and potential target for AD therapy.Data Sources：This review was based on a com...Objective：To review recent research advances on tau,a major player in Alzheimer＇s disease （AD） pathogenesis,a biomarker for AD onset,and potential target for AD therapy.Data Sources：This review was based on a comprehensive search using online literature databases,including PubMed,Web of Science,and Google Scholar.Study Selection：Literature search was based on the following keywords：Alzheimer＇s disease,tau protein,biomarker,cerebrospinal fluid （CSF）,therapeutics,plasma,imaging,propagation,spreading,seeding,prion,conformational templating,and posttranslational modification.Relevant articles were carefully reviewed,with no exclusions applied to study design and publication type.Results：Amyloid plaques enriched with extracellular amyloid beta （Aβ） and intracellular neurofibrillary tangles comprised of hyperphosphorylated tau proteins are the two main pathological hallmarks ofAD.Although the Aβ hypothesis has dominated AD research for many years,clinical Aβ-targeting strategies have consistently failed to effectively treat AD or prevent AD onset.The research focus in AD has recently shifted to the role oftau in AD.In addition to phosphorylation,tau is acetylated and proteolytically cleaved,which also contribute to its physiological and pathological functions.Emerging evidence characterizing pathological tau propagation and spreading provides new avenues for research into the molecular and cellular mechanisms underlying AD pathogenesis.Techniques to detect tau at minute levels in CSF and blood have been developed,and improved tracers have facilitated tau imaging in the brain.These advances have potential to accurately determine tau levels at early diagnostic stages in AD.Given that tau is a potential therapeutic target,anti-tau immunotherapy may potentially be a viable treatment strategy in AD intervention.Conclusion：Detecting changes in tau and targeting tau pathology represent a promising lead in the diagnosis and treatment of AD.展开更多
β-amyloid (Aβ) and copper play important roles in the pathogenesis of Alzheimer’s disease (AD).However,the behavioral correlativity and molecular mechanisms of Aβ and copper toxicity have been investigated less of...β-amyloid (Aβ) and copper play important roles in the pathogenesis of Alzheimer’s disease (AD).However,the behavioral correlativity and molecular mechanisms of Aβ and copper toxicity have been investigated less often.In the present study,we investigated the interaction and toxicity of Aβ1-42 and copper in the Aβ1-42 transgenic Caenorhabditis elegans worm model CL2006.Our data show that the paralysis behavior of CL2006 worms significantly deteriorated after exposure to 10-3 mol L-1 copper ions.However,the paralysis behavior was dramatically attenuated with exposure to 10-4 mol L-1 copper ions.The exogenous copper treatment also partially changed the homeostatic balance of zinc,manganese,and iron.Our data suggest that the accumulation of reactive oxygen species (ROS) was responsible for the paralysis induced by Aβ and copper in CL2006.The ROS generation induced by Aβ and copper appear to be through sod-1,prdx-2,skn-1,hsp-60 and hsp-16.2 genes.展开更多
Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment.The purpose of this study was to investigate the effects of mesenchymal stem cell-derived e...Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment.The purpose of this study was to investigate the effects of mesenchymal stem cell-derived exosomes on neurogenesis and cognitive capacity in a mouse model of Alzheimer’s disease.Alzheimer’s disease mouse models were established by injection of beta amyloid 1?42 aggregates into dentate gyrus bilaterally.Morris water maze and novel object recognition tests were performed to evaluate mouse cognitive deficits at 14 and 28 days after administration.Afterwards,neurogenesis in the subventricular zone was determined by immunofluorescence using doublecortin and PSA-NCAM antibodies.Results showed that mesenchymal stem cells-derived exosomes stimulated neurogenesis in the subventricular zone and alleviated beta amyloid 1?42-induced cognitive impairment,and these effects are similar to those shown in the mesenchymal stem cells.These findings provide evidence to validate the possibility of developing cell-free therapeutic strategies for Alzheimer’s disease.All procedures and experiments were approved by Institutional Animal Care and Use Committee(CICUAL)(approval No.CICUAL 2016-011)on April 25,2016.展开更多
WHO-FIC-FDRG专家委员会Stucki博士于2008年5月13日访问了中国康复研究中心康复信息研究所,并与WHO-FIC-FDRG专家邱卓英博士及其同事做了广泛交流。Stucki博士就ICF应用于康复科学体系建设以及开发基于ICF核心分类模板相关事宜做了专题...WHO-FIC-FDRG专家委员会Stucki博士于2008年5月13日访问了中国康复研究中心康复信息研究所,并与WHO-FIC-FDRG专家邱卓英博士及其同事做了广泛交流。Stucki博士就ICF应用于康复科学体系建设以及开发基于ICF核心分类模板相关事宜做了专题讲座。作为《Journal of Rehabilitation Medicine》杂志编委,Stucki博士欣然接受本刊邀请成为本刊的国际编委,并代表德国国际分类家族WHO合作中心—ICF研究分中心(ICF Research Branch of WHO Collaborating Center for the Family of International Classifications,Germany(DMIDI))与中国康复信息研究所建立有关ICF研究国际合作,建立了《Journal of Rehabilitation Medicine》和《中国康复理论与实践》杂志间的学术联系。本专题的英文文章发表于《Journal of Rehabilitation Medicine》,由Stucki教授授权《中国康复理论与实践》杂志以中文形式独家发表。第一篇是由中外专家专门为本刊撰写的特稿。本专题的文章是在相关专家组织下翻译的,内容涉及基于ICF的康复学科体系的建立,面向功能的整合性康复学科体系的发展,从细胞到社会的功能结构分类摸板,基于ICF重新定义康复医学、康复科学和康复服务,以及开发应用于不同康复医疗领域的ICF核心分类等内容。这些研究反应了国际最新的理论和应用发展成果,对于依据ICF这一国际性的功能残疾模式和知识分类标准,建立符合科学发展规律和社会发展要求的学科体系以及实践领域具有十分重要的理论和实践意义。通过出版本专题,希望能使广大康复科技工作者关注国际相关发展,更新有关观念和方法,推动康复科学学科建设和发展,扩大国际合作与交流。鉴于ICF理论与方法相对较新,本专题中很多文章从科学学和方法论角度探讨学科建设和知识体系的构建,有的内容涉及到专业性很强的测量学方法,这些对于专题译校团队的专家学者也是�展开更多
Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum...Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.展开更多
We characterized a unique group of patients with neuromyelitis optica spectrum disorder （NMOSD） who carded autoantibod- ies of aquaporin-4 （AQP4） and myelin-oligodendrocyte glycoprotein （MOG）. Among the 125 NMOS...We characterized a unique group of patients with neuromyelitis optica spectrum disorder （NMOSD） who carded autoantibod- ies of aquaporin-4 （AQP4） and myelin-oligodendrocyte glycoprotein （MOG）. Among the 125 NMOSD patients, 10 （8.0%） were AQP4- and MOG-ab double positive, and 14 （11.2%） were MOG-ab single positive. The double-positive patients had a multiphase disease course with a high annual relapse rate （P=0.0431）, and severe residual disability （P〈0.0001）. Of the dou- ble-positive patients, 70% had MS-like brain lesions, more severe edematous, multifocal regions on spinal magnetic resonance imaging （MRI）, pronounced decreases of retinal nerve fiber layer thickness and atrophy of optic nerves. In contrast, patients with only MOG-ab had a higher ratio of monophasic disease course and mild residual disability. Spinal cord MRI illustrated multifocal cord lesions with mild edema, and brain MRIs showed more lesions around lateral ventricles. NMOSD patients carrying both autoantibodies to AQP4 and MOG existed and exhibited combined features of prototypic NMO and relaps- ing-remitting form of MS, whereas NMOSD with antibodies to MOG only exhibited an ＂intermediate＂ phenotype between NMOSD and MS. Our study suggests that antibodies against MOG might be pathogenic in NMOSD patients and that determi- nation of anti-MOG antibodies maybe instructive for management of NMOSD patients.展开更多
Alzheimer＇s disease （AD） is the most common type of dementia, comprising an estimated 60-80% of all dementia cases. It is clinically characterized by impairments of memory and other cognitive functions. Previous st...Alzheimer＇s disease （AD） is the most common type of dementia, comprising an estimated 60-80% of all dementia cases. It is clinically characterized by impairments of memory and other cognitive functions. Previous studies have demonstrated that these impairments are associated with abnormal structural and functional connections among brain regions, leading to a disconnection concept of AD. With the advent of a combination of non-invasive neuroimaging （structural magnetic resonance imaging （MRI）, diffusion MRI, and functional MRI） and neurophysiological techniques （electroencephalography and magnetoencephaJography） with graph theoretical analysis, recent studies have shown that patients with AD and mild cognitive impairment （MCI）, the prodromal stage of AD, exhibit disrupted topological organization in large-scale brain networks （i.e., connectomics） and that this disruption is significantly correlated with the decline of cognitive functions. In this review, we summarize the recent progress of brain connectomics in AD and MCI, focusing on the changes in the topological organization of large-scale structural and functional brain networks using graph theoretical approaches. Based on the two different perspectives of information segregation and integration, the literature reviewed here suggests that AD and MCI are associated with disrupted segregation and integration in brain networks. Thus, these connectomics studies open up a new window for understanding the pathophysiological mechanisms of AD and demonstrate the potential to uncover imaging biomarkers for clinical diagnosis and treatment evaluation for this disease.展开更多
Gene editing in model organisms has provided critical insights into brain development and diseases. Here, we report the generation of a cynomolgus monkey （Macaca fascicularis） carrying MECP2 mutations using transcri...Gene editing in model organisms has provided critical insights into brain development and diseases. Here, we report the generation of a cynomolgus monkey （Macaca fascicularis） carrying MECP2 mutations using transcription activator-like effector nucleases （TALENs）-mediated gene targeting. After injecting TALENs mRNA into monkey zygotes achieved by in vitro fertilization and embryo transplantation into surrogate monkeys, we obtained one male newborn monkey with an MECP2 deletion caused by frame- shifting mutation in various tissues. The monkey carrying the MECP2 mutation failed to survive after birth, due to either the toxicity of TALENs or the critical requirement of MECP2 for neural development. The level of MeCP2 protein was essentially depleted in the monkey＇s brain. This study demonstrates the feasibility of introducing genetic mutations in non-human primates by site-specific gene-editing methods.展开更多
Perinatal complications,such as asphyxia,can cause brain injuries that are often associated with subsequent neurological deficits,such as cerebral palsy or mental retardation.The mechanisms of perinatal brain injury a...Perinatal complications,such as asphyxia,can cause brain injuries that are often associated with subsequent neurological deficits,such as cerebral palsy or mental retardation.The mechanisms of perinatal brain injury are not fully understood,but mitochondria play a prominent role not only due to their central function in metabolism but also because many proteins with apoptosis-related functions are located in the mitochondrion.Among these proteins,apoptosis-inducing factor has already been shown to be an important factor involved in neuronal cell death upon hypoxia-ischemia,but a better understanding of the mechanisms behind these processes is required for the development of more effective treatments during the early stages of perinatal brain injury.In this review,we focus on the molecular mechanisms of hypoxic-ischemic encephalopathy,specifically on the importance of apoptosis-inducing factor.The relevance of apoptosis-inducing factor is based not only because it participates in the caspase-independent apoptotic pathway but also because it plays a crucial role in mitochondrial energetic functionality,especially with regard to the maintenance of electron transport during oxidative phosphorylation and in oxidative stress,acting as a free radical scavenger.We also discuss all the different apoptosis-inducing factor isoforms discovered,focusing especially on apoptosis-inducing factor 2,which is only expressed in the brain and the functions of which are starting now to be clarified.Finally,we summarized the interaction of apoptosis-inducing factor with several proteins that are crucial for both apoptosis-inducing factor functions(prosurvival and pro-apoptotic)and that are highly important in order to develop promising therapeutic targets for improving outcomes after perinatal brain injury.展开更多
Brain-derived neurotrophic factor(BDNF) regulates many neurological functions and plays a vital role during the recovery from central nervous system injuries. However, the changes in BDNF expression and associated fac...Brain-derived neurotrophic factor(BDNF) regulates many neurological functions and plays a vital role during the recovery from central nervous system injuries. However, the changes in BDNF expression and associated factors following hypoxia-ischemia induced neonatal brain damage, and the significance of these changes are not fully understood. In the present study, a rat model of hypoxic-ischemic brain damage was established through the occlusion of the right common carotid artery, followed by 2 hours in a hypoxic-ischemic environment. Rats with hypoxic-ischemic brain damage presented deficits in both sensory and motor functions, and obvious pathological changes could be detected in brain tissues. The m RNA expression levels of BDNF and its processing enzymes and receptors(Furin, matrix metallopeptidase 9, tissuetype plasminogen activator, tyrosine Kinase receptor B, plasminogen activator inhibitor-1, and Sortilin) were upregulated in the ipsilateral hippocampus and cerebral cortex 6 hours after injury;however, the expression levels of these m RNAs were found to be downregulated in the contralateral hippocampus and cerebral cortex. These findings suggest that BDNF and its processing enzymes and receptors may play important roles in the pathogenesis and recovery from neonatal hypoxic-ischemic brain damage. This study was approved by the Animal Ethics Committee of the University of South Australia(approval No. U12-18) on July 30, 2018.展开更多
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.
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.
文摘One of the most important points in the meta-analyses is certainly represented by the assessment of the quality of the studies included in such research. The meta-analyses are considered the highest level of evidence in science. Also for this reason, the quality of the studies included should be accurately evaluated by standardized tools. The overall results of the metaanalysis depend indeed also on a rigorous evaluation of the studies quality. Among all the possible tools for this complex evaluation, the Newcastle Ottawa Scale(NOS) is one of the most used worldwide, above all for observational studies. In this review, we will discuss the strengths and limitation of the NOS, also on the basis of the branch of science in which it has been applied.
文摘INTRODUCTION Sleep disturbance is one of the most common nonmotor symptoms in Parkinson's disease (PD).Sleep disturbance affects 40-98% of PD patients in the world. In China, the prevalence of PD patients with sleep disturbance ranges from 47.66% to 89.10%. Sleep disturbance usually has adverse impact on the quality of life of PD patients. Apossible pathogenesis of PD with sleep disturbance include thalamocortical pathway degeneration and changes of neurotransmitter systems. The etiology of sleep disturbance is multifactorial,involving degeneration of areas regulating sleep,sleep structure affected by drugs,sleep disturbance induced by drug,and sleep fragmentation by multiple factors.
基金supported by The National Natural Science Foundation of China(Grant No.81702972,Grant No.81874204)China Postdoctoral Science Foundation(Grant No.2018M640305,Grant No.2019M660074)+4 种基金The Research Project of the Chinese Society of Neuro-oncology,CACA(Grant No.CSNO-2016-MSD12)Heilongjiang Postdoctoral Science Foundation(Grant No.LBH-Z18103)The Research Project of the Health and Family Planning Commission of Heilongjiang Province(Grant No.2017–201)Postgraduate Research&Practice Innovation Program of Harbin Medical University(Grant No.YJSKYCX2018-94HYD)The Young and middle-aged Science Foundation of Harbin Medical University(Grant No.KYCX2018-08)。
文摘Objective:Neutrophil extracellular traps(NETs)produced by tumor-infiltrating neutrophils(TINs)are associated with poor prognosis in patients with several types of cancer.However,the mechanisms underlying the involvement of NETs in glioma progression remain largely unknown.This study aimed to elucidate the roles of NETs in biological processes that drive the crosstalk between glioma progression and the tumor microenvironment.Methods:Neutrophil infiltration and NETs formation were investigated in glioma tissue through immunohistochemistry,and their relationships with clinicopathological features and outcomes were statistically evaluated.The effects of NETs on glioma cell progression were studied in a co-culture system.In vivo and in vitro experiments validated the reactive oxygen species activity and cytokine production of TINs,as well as the ERK signaling pathway activation and the metastasis of gliomas.Results:Neutrophil infiltration and NETs formation were induced in high-grade glioma compared with low-grade glioma.NETs induced by TINs were determined to be an oncogenic marker of high-grade gliomas and to be involved in cell proliferation and invasion.NETs overproduction promoted glioma cell proliferation,migration,and invasion.Furthermore,HMGB1 was found to bind to RAGE and activate the NF-κB signaling pathway in vitro.In addition,NETs stimulated the NF-κB signaling pathway,thus promoting IL-8 secretion in glioblastoma.Subsequently,IL-8 recruited neutrophils which in turn mediated NETs formation via the PI3 K/AKT/ROS axis in TINs.Conclusions:Our results suggest that NETs produced by TINs mediate the crosstalk between glioma progression and the tumor microenvironment by regulating the HMGB1/RAGE/IL-8 axis.Targeting NETs formation or IL-8 secretion may be an effective approach to inhibit glioma progression.
基金Project supported by the Special Research Fund for the Public Welfare Industry of Health of China(No.201302013)
文摘Abstract： With the rapid development of assisted reproductive technology, various reproductive disorders have been effectively addressed. Acupuncture-like therapies, including electroacupuncture （EA） and transcutaneous electrical acupoint stimulation （TEAS）, become more popular world-wide. Increasing evidence has demonstrated that EA and TEAS are effective in treating gynecological disorders, especially infertility. This present paper describes how to select acupoints for the treatment of infertility from the view of theories of traditional Chinese medicine and how to determine critical parameters of electric pulses of ENTEAS based on results from animal and clinical studies. It summarizes the principles of clinical application of EA/rEAS in treating various kinds of reproductive disorders, such as polycystic ovary syndrome （PCOS）, pain induced by oocyte retrieval, diminished ovarian reserve, embryo transfer, and oligosperrnia/ asthenospermia. The possible underlying mechanisms mediating the therapeutic effects of EA/TEAS in reproductive medicine are also examined.
文摘Gradual degeneration and loss of dopaminergic neurons in the substantia nigra,pars compacta and subsequent reduction of dopamine levels in striatum are associated with motor deficits that characterize Parkinson’s disease(PD).In addition,half of the PD patients also exhibit frontostriatal-mediated executive dysfunction,including deficits in attention,short-term working memory,speed of mental processing,and impulsivity.The most commonly used treatments for PD are only partially or transiently effective and are available or applicable to a minority of patients.Because,these therapies neither restore the lost or degenerated dopaminergic neurons,nor prevent or delay the disease progression,the need for more effective therapeutics is critical.In this review,we provide a comprehensive overview of the current understanding of the molecular signaling pathways involved in PD,particularly within the context of how genetic and environmental factors contribute to the initiation and progression of this disease.The involvement of molecular chaperones,autophagy-lysosomal pathways,and proteasome systems in PD are also highlighted.In addition,emerging therapies,including pharmacological manipulations,surgical procedures,stem cell transplantation,gene therapy,as well as complementary,supportive and rehabilitation therapies to prevent or delay the progression of this complex disease are reviewed.
文摘AIM: To assess the impact of percutaneous cardiac support in cardiogenic shock(CS) complicating acute myocardial infarction(AMI), treated with percutaneous coronary intervention. METHODS: We selected all of the studies published from January 1st, 1997 to May 15 st, 2015 that compared the following percutaneous mechanical support in patients with CS due to AMI undergoing myocardial revascularization:(1) intra-aortic balloon pump(IABP) vs Medical therapy;(2) percutaneous left ventricular assist devices(PLVADs) vs IABP;(3) complete extracorporeal life support with extracorporeal membrane oxygenation(ECMO) plus IABP vs IABP alone; and(4) ECMO plus IABP vs ECMO alone, in patients with AMI and CS undergoing myocardial revascularization. We evaluated the impact of the support devices on primary and secondary endpoints. Primary endpoint was the inhospital mortality due to any cause during the same hospital stay and secondary endpoint late mortality at 6-12 moof follow-up. RESULTS: One thousand two hundred and seventytwo studies met the initial screening criteria. After detailed review, only 30 were selected. There were 6 eligible randomized controlled trials and 24 eligible observational studies totaling 15799 patients. We found that the inhospital mortality was:(1) significantly higher with IABP support vs medical therapy(RR = +15%, P = 0.0002);(2) was higher, although not significantly, with PLVADs compared to IABP(RR = +14%, P = 0.21); and(3) significantly lower in patients treated with ECMO plus IABP vs IABP(RR =-44%, P = 0.0008) or ECMO(RR =-20%, P = 0.006) alone. In addition, Trial Sequential Analysis showed that in the comparison of IABP vs medical therapy, the sample size was adequate to demonstrate a significant increase in risk due to IABP. CONCLUSION: Inhospital mortality was significantly higher with IABP vs medical therapy. PLVADs did not reduce early mortality. ECMO plus IABP significantly reduced inhospital mortality compared to IABP.
文摘Background The incidence of spinal injury with spinal cord contusion is high in developed countries and is now growing in China. Furthermore, spinal cord injury happens mostly in young people who have a long life expectance. A large number of patients thus are wheelchair bound for the rest of their lives. Therefore, spinal cord injury has aroused great concern worldwide. Despite great efforts, recovery from spinal cord injury remains unsatisfactory. Based on the pathology of spinal cord contusion, an idea of early neurosurgical intervention has been formulated in this study. Methods A total of 30 patients with ＂complete＂ spinal cord injury or classified as American Spinal Injury Association （ASIA）-A were studied. Orthopedic treatment of the injured vertebra（e）, internal fixation of the vertebral column, and bilateral laminectomy for epidural decompression were followed directly by neurosurgical management, including separation of the arachnoid adhesion to restore cerebrospinal fluid flow and debridement of the spinal cord necrotic tissue with concomitant intramedullary decompression. Rehabilitation started 17 days after the operation. The final outcome was evaluated after 3 months of rehabilitation. Pearson chi-square analysis was used for statistical analysis. Results All the patients recovered some ability to walk. The least recovered patients were able to walk with a wheeled weight support and help in stabilizing the weight bearing knee joint （12 cases, 40%）. Thirteen patients （43%） were able to walk with a pair of crutches, a stick or without any support. The timing of the operation after injury was important. An optimal operation time window was identified at 4-14 days after injury. Conclusions Early neurosurgical intervention of spinal cord contusion followed by rehabilitation can significantly improve the locomotion of the patients. It is a new idea of a therapeutic approach for spinal cord contusion and has been proven to be very successful.
基金This work was supported by grants from the National Natural Science Foundation of China （No. 81671352, 91232709）, the National Key Project of Research and Development Plan （No. 2016YFC1306404）, the National Institute of Health （No. R21 AG048519, R01 AG021173, R01 AG038710, R01 AG044420, R01 NS046673, RF1 AG056130, and RF1 AG056114）, the Tanz Family Fund as well as scholarship from China Scholarship Council （No. 201608350068）.
文摘Objective：To review recent research advances on tau,a major player in Alzheimer＇s disease （AD） pathogenesis,a biomarker for AD onset,and potential target for AD therapy.Data Sources：This review was based on a comprehensive search using online literature databases,including PubMed,Web of Science,and Google Scholar.Study Selection：Literature search was based on the following keywords：Alzheimer＇s disease,tau protein,biomarker,cerebrospinal fluid （CSF）,therapeutics,plasma,imaging,propagation,spreading,seeding,prion,conformational templating,and posttranslational modification.Relevant articles were carefully reviewed,with no exclusions applied to study design and publication type.Results：Amyloid plaques enriched with extracellular amyloid beta （Aβ） and intracellular neurofibrillary tangles comprised of hyperphosphorylated tau proteins are the two main pathological hallmarks ofAD.Although the Aβ hypothesis has dominated AD research for many years,clinical Aβ-targeting strategies have consistently failed to effectively treat AD or prevent AD onset.The research focus in AD has recently shifted to the role oftau in AD.In addition to phosphorylation,tau is acetylated and proteolytically cleaved,which also contribute to its physiological and pathological functions.Emerging evidence characterizing pathological tau propagation and spreading provides new avenues for research into the molecular and cellular mechanisms underlying AD pathogenesis.Techniques to detect tau at minute levels in CSF and blood have been developed,and improved tracers have facilitated tau imaging in the brain.These advances have potential to accurately determine tau levels at early diagnostic stages in AD.Given that tau is a potential therapeutic target,anti-tau immunotherapy may potentially be a viable treatment strategy in AD intervention.Conclusion：Detecting changes in tau and targeting tau pathology represent a promising lead in the diagnosis and treatment of AD.
基金supported by the National Natural Science Foundation of China (Grant No. 30870578)the National Basic Research Program of China (Grant No. 2006CB500700)funded by the US National Institutes of Health for providing nematode strains used in this work
文摘β-amyloid (Aβ) and copper play important roles in the pathogenesis of Alzheimer’s disease (AD).However,the behavioral correlativity and molecular mechanisms of Aβ and copper toxicity have been investigated less often.In the present study,we investigated the interaction and toxicity of Aβ1-42 and copper in the Aβ1-42 transgenic Caenorhabditis elegans worm model CL2006.Our data show that the paralysis behavior of CL2006 worms significantly deteriorated after exposure to 10-3 mol L-1 copper ions.However,the paralysis behavior was dramatically attenuated with exposure to 10-4 mol L-1 copper ions.The exogenous copper treatment also partially changed the homeostatic balance of zinc,manganese,and iron.Our data suggest that the accumulation of reactive oxygen species (ROS) was responsible for the paralysis induced by Aβ and copper in CL2006.The ROS generation induced by Aβ and copper appear to be through sod-1,prdx-2,skn-1,hsp-60 and hsp-16.2 genes.
基金sponsored by CONACYT scholarship#487713Fondo Mixto de Ciencia y Tecnología del Estado de Jalisco grant JAL-2014-0-250508
文摘Studies have shown that mesenchymal stem cell-derived exosomes can enhance neural plasticity and improve cognitive impairment.The purpose of this study was to investigate the effects of mesenchymal stem cell-derived exosomes on neurogenesis and cognitive capacity in a mouse model of Alzheimer’s disease.Alzheimer’s disease mouse models were established by injection of beta amyloid 1?42 aggregates into dentate gyrus bilaterally.Morris water maze and novel object recognition tests were performed to evaluate mouse cognitive deficits at 14 and 28 days after administration.Afterwards,neurogenesis in the subventricular zone was determined by immunofluorescence using doublecortin and PSA-NCAM antibodies.Results showed that mesenchymal stem cells-derived exosomes stimulated neurogenesis in the subventricular zone and alleviated beta amyloid 1?42-induced cognitive impairment,and these effects are similar to those shown in the mesenchymal stem cells.These findings provide evidence to validate the possibility of developing cell-free therapeutic strategies for Alzheimer’s disease.All procedures and experiments were approved by Institutional Animal Care and Use Committee(CICUAL)(approval No.CICUAL 2016-011)on April 25,2016.
文摘WHO-FIC-FDRG专家委员会Stucki博士于2008年5月13日访问了中国康复研究中心康复信息研究所,并与WHO-FIC-FDRG专家邱卓英博士及其同事做了广泛交流。Stucki博士就ICF应用于康复科学体系建设以及开发基于ICF核心分类模板相关事宜做了专题讲座。作为《Journal of Rehabilitation Medicine》杂志编委,Stucki博士欣然接受本刊邀请成为本刊的国际编委,并代表德国国际分类家族WHO合作中心—ICF研究分中心(ICF Research Branch of WHO Collaborating Center for the Family of International Classifications,Germany(DMIDI))与中国康复信息研究所建立有关ICF研究国际合作,建立了《Journal of Rehabilitation Medicine》和《中国康复理论与实践》杂志间的学术联系。本专题的英文文章发表于《Journal of Rehabilitation Medicine》,由Stucki教授授权《中国康复理论与实践》杂志以中文形式独家发表。第一篇是由中外专家专门为本刊撰写的特稿。本专题的文章是在相关专家组织下翻译的,内容涉及基于ICF的康复学科体系的建立,面向功能的整合性康复学科体系的发展,从细胞到社会的功能结构分类摸板,基于ICF重新定义康复医学、康复科学和康复服务,以及开发应用于不同康复医疗领域的ICF核心分类等内容。这些研究反应了国际最新的理论和应用发展成果,对于依据ICF这一国际性的功能残疾模式和知识分类标准,建立符合科学发展规律和社会发展要求的学科体系以及实践领域具有十分重要的理论和实践意义。通过出版本专题,希望能使广大康复科技工作者关注国际相关发展,更新有关观念和方法,推动康复科学学科建设和发展,扩大国际合作与交流。鉴于ICF理论与方法相对较新,本专题中很多文章从科学学和方法论角度探讨学科建设和知识体系的构建,有的内容涉及到专业性很强的测量学方法,这些对于专题译校团队的专家学者也是�
基金supported by the National Natural Science Foundation of China(31730036,31871380,31871382,31930055,31930058,32000500,32022034,32030033,32070730,32130046,3217050247,32150005,32200595,32222024,81730019,81730022,81830014,81921006,81925005,81970426,81971301,81971312,82030041,82061160495,82070805,82071595,82090020,82100841,82120108009,82122024,82125002,82125011,82125012,82130045,82171284,82173061,82173398,82225007,82225015,82225017,82225018,82230047,82230088,82271600,91949106,91949201,92049116,92049302,92049304,92149303,92149306,92157202,92168201,92169102,92249301,92268201)the National Key Research and Development Program of China(2018YFA0800700,2018YFC2000100,2018YFC2000102,2018YFC2002003,2019YFA0110900,2019YFA0801703,2019YFA0801903,2019YFA0802202,2019YFA0904800,2020YFA0113400,2020YFA0803401,2020YFA0804000,2020YFC2002900,2020YFC2008000,2020YFE0202200,2021YFA0804900,2021YFA1100103,2021YFA1100900,2021YFE0114200,2021ZD0202400,2022YFA0806001,2022YFA0806002,2022YFA0806600,2022YFA1103200,2022YFA1103601,2022YFA1103701,2022YFA1103800,2022YFA1103801,2022YFA1104100,2022YFA1104904,2022YFA1303000,2022YFC2009900,2022YFC2502401,2022YFC3602400,2022YFE0118000,2022ZD0213200)+9 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16030302,XDB39000000,XDB39030600)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2020085,2021080)CAS Project for Young Scientists in Basic Research(YSBR-076)the Program of the Beijing Natural Science Foundation(JQ20031)Clinical Research Operating Fund of Central High level hospitals(2022-PUMCHE-001)CAMS Innovation Fund for Medical Sciences(CIFMS)(2022-I2M1-004)Talent Program of the Chinese Academy of Medical Science(2022RC310-10)Research Funds from Health@Inno HK Program launched by Innovation Technology Commission of the Hong Kong Special Administrative Region,Guangdong Basic and Applied Basic Research Foundation(2020B1515020044)Guangzhou Planned Project of Science and Technology(202002020039)the Major Technology Innovation of Hubei Province(2019ACA14
文摘Aging biomarkers are a combination of biological parameters to(i)assess age-related changes,(ii)track the physiological aging process,and(iii)predict the transition into a pathological status.Although a broad spectrum of aging biomarkers has been developed,their potential uses and limitations remain poorly characterized.An immediate goal of biomarkers is to help us answer the following three fundamental questions in aging research:How old are we?Why do we get old?And how can we age slower?This review aims to address this need.Here,we summarize our current knowledge of biomarkers developed for cellular,organ,and organismal levels of aging,comprising six pillars:physiological characteristics,medical imaging,histological features,cellular alterations,molecular changes,and secretory factors.To fulfill all these requisites,we propose that aging biomarkers should qualify for being specific,systemic,and clinically relevant.
基金supported by National Basic Research Program of China Grant (2013CB96690)the Natural Science Foundation of China Grants (81100888, 81230028, 81371372)+2 种基金the National Key Clinical Specialty Construction Program of ChinaUS National Institute of Health (R01AI083294)the American Heart Association (14GRNT18970031)
文摘We characterized a unique group of patients with neuromyelitis optica spectrum disorder （NMOSD） who carded autoantibod- ies of aquaporin-4 （AQP4） and myelin-oligodendrocyte glycoprotein （MOG）. Among the 125 NMOSD patients, 10 （8.0%） were AQP4- and MOG-ab double positive, and 14 （11.2%） were MOG-ab single positive. The double-positive patients had a multiphase disease course with a high annual relapse rate （P=0.0431）, and severe residual disability （P〈0.0001）. Of the dou- ble-positive patients, 70% had MS-like brain lesions, more severe edematous, multifocal regions on spinal magnetic resonance imaging （MRI）, pronounced decreases of retinal nerve fiber layer thickness and atrophy of optic nerves. In contrast, patients with only MOG-ab had a higher ratio of monophasic disease course and mild residual disability. Spinal cord MRI illustrated multifocal cord lesions with mild edema, and brain MRIs showed more lesions around lateral ventricles. NMOSD patients carrying both autoantibodies to AQP4 and MOG existed and exhibited combined features of prototypic NMO and relaps- ing-remitting form of MS, whereas NMOSD with antibodies to MOG only exhibited an ＂intermediate＂ phenotype between NMOSD and MS. Our study suggests that antibodies against MOG might be pathogenic in NMOSD patients and that determi- nation of anti-MOG antibodies maybe instructive for management of NMOSD patients.
基金supported by National Key Basic Research Program of China(2014CB846102)Natural Science Foundation of China(81030028 and 31221003)+1 种基金Beijing Natural Science Foundation(Z111107067311036)National Science Fund for Distinguished Young Scholars(81225012)
文摘Alzheimer＇s disease （AD） is the most common type of dementia, comprising an estimated 60-80% of all dementia cases. It is clinically characterized by impairments of memory and other cognitive functions. Previous studies have demonstrated that these impairments are associated with abnormal structural and functional connections among brain regions, leading to a disconnection concept of AD. With the advent of a combination of non-invasive neuroimaging （structural magnetic resonance imaging （MRI）, diffusion MRI, and functional MRI） and neurophysiological techniques （electroencephalography and magnetoencephaJography） with graph theoretical analysis, recent studies have shown that patients with AD and mild cognitive impairment （MCI）, the prodromal stage of AD, exhibit disrupted topological organization in large-scale brain networks （i.e., connectomics） and that this disruption is significantly correlated with the decline of cognitive functions. In this review, we summarize the recent progress of brain connectomics in AD and MCI, focusing on the changes in the topological organization of large-scale structural and functional brain networks using graph theoretical approaches. Based on the two different perspectives of information segregation and integration, the literature reviewed here suggests that AD and MCI are associated with disrupted segregation and integration in brain networks. Thus, these connectomics studies open up a new window for understanding the pathophysiological mechanisms of AD and demonstrate the potential to uncover imaging biomarkers for clinical diagnosis and treatment evaluation for this disease.
基金supported by the National Basic Research Development Program of China (2011CBA00400 and 2011CB809102)the CAS Strategic Priority Research Program of China (XDB02050400)+2 种基金the National Key Technology R&D Program of China (2014BAI03B00)the CAS Hundreds of Talents Program of China (to Z.Q. and Q.S.)the National Science Foundation of China (91232712)
文摘Gene editing in model organisms has provided critical insights into brain development and diseases. Here, we report the generation of a cynomolgus monkey （Macaca fascicularis） carrying MECP2 mutations using transcription activator-like effector nucleases （TALENs）-mediated gene targeting. After injecting TALENs mRNA into monkey zygotes achieved by in vitro fertilization and embryo transplantation into surrogate monkeys, we obtained one male newborn monkey with an MECP2 deletion caused by frame- shifting mutation in various tissues. The monkey carrying the MECP2 mutation failed to survive after birth, due to either the toxicity of TALENs or the critical requirement of MECP2 for neural development. The level of MeCP2 protein was essentially depleted in the monkey＇s brain. This study demonstrates the feasibility of introducing genetic mutations in non-human primates by site-specific gene-editing methods.
基金the Swedish Research Council(2018-02667)the National Natural Science Foundation of China(31761133015,U1704281,81901335)+3 种基金the Swedish Childhood Cancer Foundation(PR2018-0082)Swedish Governmental Grants to Scientists Working in Health Care(ALFGBG-717791)the Swedish Brain Foundation(FO2018-0034)the Chinese Scholarship Council to TL(201707040025)and to YX(201507040082)。
文摘Perinatal complications,such as asphyxia,can cause brain injuries that are often associated with subsequent neurological deficits,such as cerebral palsy or mental retardation.The mechanisms of perinatal brain injury are not fully understood,but mitochondria play a prominent role not only due to their central function in metabolism but also because many proteins with apoptosis-related functions are located in the mitochondrion.Among these proteins,apoptosis-inducing factor has already been shown to be an important factor involved in neuronal cell death upon hypoxia-ischemia,but a better understanding of the mechanisms behind these processes is required for the development of more effective treatments during the early stages of perinatal brain injury.In this review,we focus on the molecular mechanisms of hypoxic-ischemic encephalopathy,specifically on the importance of apoptosis-inducing factor.The relevance of apoptosis-inducing factor is based not only because it participates in the caspase-independent apoptotic pathway but also because it plays a crucial role in mitochondrial energetic functionality,especially with regard to the maintenance of electron transport during oxidative phosphorylation and in oxidative stress,acting as a free radical scavenger.We also discuss all the different apoptosis-inducing factor isoforms discovered,focusing especially on apoptosis-inducing factor 2,which is only expressed in the brain and the functions of which are starting now to be clarified.Finally,we summarized the interaction of apoptosis-inducing factor with several proteins that are crucial for both apoptosis-inducing factor functions(prosurvival and pro-apoptotic)and that are highly important in order to develop promising therapeutic targets for improving outcomes after perinatal brain injury.
基金supported by the National Natural Science Foundation of China,No. 82001604 (to LLX)the Joint Subject of Southwest Medical University and Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University of China,No. 2018XYLH-004 (to LLX)+1 种基金the National Construction Project of Regional Chinese Medicine Treatment Centre of China,No. 2018205 (to XB)the National Construction Project of the Second Clinical Research Base of Chinese Medicine of China,No. 2018131 (to XB)。
文摘Brain-derived neurotrophic factor(BDNF) regulates many neurological functions and plays a vital role during the recovery from central nervous system injuries. However, the changes in BDNF expression and associated factors following hypoxia-ischemia induced neonatal brain damage, and the significance of these changes are not fully understood. In the present study, a rat model of hypoxic-ischemic brain damage was established through the occlusion of the right common carotid artery, followed by 2 hours in a hypoxic-ischemic environment. Rats with hypoxic-ischemic brain damage presented deficits in both sensory and motor functions, and obvious pathological changes could be detected in brain tissues. The m RNA expression levels of BDNF and its processing enzymes and receptors(Furin, matrix metallopeptidase 9, tissuetype plasminogen activator, tyrosine Kinase receptor B, plasminogen activator inhibitor-1, and Sortilin) were upregulated in the ipsilateral hippocampus and cerebral cortex 6 hours after injury;however, the expression levels of these m RNAs were found to be downregulated in the contralateral hippocampus and cerebral cortex. These findings suggest that BDNF and its processing enzymes and receptors may play important roles in the pathogenesis and recovery from neonatal hypoxic-ischemic brain damage. This study was approved by the Animal Ethics Committee of the University of South Australia(approval No. U12-18) on July 30, 2018.
