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
Ischemic stroke is a common disease with high mortality and morbidity worldwide.One of the important pathophysiological effects of ischemic stroke is apoptosis.A neuroprotective effect is defined as the inhibition of ...Ischemic stroke is a common disease with high mortality and morbidity worldwide.One of the important pathophysiological effects of ischemic stroke is apoptosis.A neuroprotective effect is defined as the inhibition of neuronal apoptosis to rescue or delay the infarction in the surviving ischemic penumbra.Resveratrol is a natural polyphenol that reportedly prevents cerebral ischemia injury by regulating the expression of PI3K/AKT/mTOR.Therefore,this study aimed to elucidate the neuroprotective effect of resveratrol on cerebral ischemia/reperfusion injury and to investigate the signaling pathways and mechanisms through which resveratrol regulates apoptosis in the ischemic penumbra.Rats were subjected to middle cerebral artery occlusion for 2 h followed by 24 h reperfusion.Cerebral infarct volume was measured using 2%TTC staining.TUNEL staining was conducted to evaluate neuronal apoptosis.Western blotting and immunohistochemistry were used to detect the proteins involved in the JAK2/STAT3/PI3K/AKT/mTOR pathway.The results suggested that resveratrol significantly improved neurological function,reduced cerebral infarct volume,decreased neuronal damage,and markedly attenuated neuronal apoptosis;these effects were attenuated by the inhibition of PI3K/AKT with LY294002 and JAK2/STAT3 with AG490.We also found that resveratrol significantly upregulated the expression of p-JAK2,p-STAT3,p-AKT,p-mTOR,and BCL-2 and downregulated expression of cleaved caspase-3 and BAX,which was partially reversed by LY294002 and AG490.These results suggested that resveratrol provides a neuroprotective effect against cerebral ischemia/reperfusion injury,which is partially mediated by the activation of JAK2/STAT3 and PI3K/AKT/mTOR.Resveratrol may indirectly upregulate the PI3K/AKT/mTOR pathway by activating JAK2/STAT3.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
Ferroptosis is an iron-dependent cell death,which is different from apoptosis,necrosis,autophagy,and other forms of cell death.The process of feroptotic cell death is defined by the accumulation of lethal lipid specie...Ferroptosis is an iron-dependent cell death,which is different from apoptosis,necrosis,autophagy,and other forms of cell death.The process of feroptotic cell death is defined by the accumulation of lethal lipid species derived from the peroxidation of lipids,which can be prevented by iron chelators(e.g.deferiprone,deferoxamine)and small lipophilic antioxidants(e.g,ferrostatin,liproxstatin).This review summarizes current knowledge about the regulatory mechanism of ferroptosis and its association withseveral pathways,including iron,lipid,and cysteine metabolism.We have further discussed the contribution of ferroptosis to thepathogenesis of several diseases such as cancer,ischemia/reperfusion,and various neurodegenerative diseases(e.g.Alzheimersdisease and Parkinson's disease),and evaluated the therapeutic applications of ferroptosis inhibitors in clinics.展开更多
The gastrointestinal(GI) barrier serves a critical role in survival and overall health of animals and humans. Several layers of barrier defense mechanisms are provided by the epithelial, immune and enteric nervous sys...The gastrointestinal(GI) barrier serves a critical role in survival and overall health of animals and humans. Several layers of barrier defense mechanisms are provided by the epithelial, immune and enteric nervous systems. Together they act in concert to control normal gut functions(e.g., digestion,absorption, secretion, immunity, etc.) whereas at the same time provide a barrier from the hostile conditions in the luminal environment. Breakdown of these critical GI functions is a central pathophysiological mechanism in the most serious GI disorders in pigs. This review will focus on the development and functional properties of the GI barrier in pigs and how common early life production stressors, such as weaning, can alter immediate and long-term barrier function and disease susceptibility.Specific stress-related pathophysiological mechanisms responsible for driving GI barrier dysfunction induced by weaning and the implications to animal health and performance will be discussed.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
Background： Autoimmune encephalitis associated with antibodies against γ-aminobutyric acid B receptor （GABABR） in patients with limbic encephalitis （LE） was first described in 2010. We present a series of klan C...Background： Autoimmune encephalitis associated with antibodies against γ-aminobutyric acid B receptor （GABABR） in patients with limbic encephalitis （LE） was first described in 2010. We present a series of klan Chinese patients tbr further clinical refinement. Methods： Serum and cerebrospinal fluid （CSF） samples from patients referred to the program of encephalitis and paraneoplastic syndrome of Peking Union Medical College Hospital were tested with indirect immunofluorescence. Clinical information of patients with anti-GABABR antibody positivity was retrospectively reviewed, and descriptive statistical analysis was performed. Results： All eighteen anti-GABABR antibody-positive cases had limbic syndromes, and electroencephalogram （EEG） or neuroimaging evidence fulfilled the diagnostic criteria of LE. Four patients had additional antibodies against Hu in serum and one had anti-N-methyl-d-aspartate receptor antibody in both sera and CSF. Seventeen （17/18） patients presented with new-onset refractory seizure or status epileptics. Twelve （12/18） patients had memory deficits, 11 （11/18） patients had personality change, 7 （7/18） patients had disturbance of consciousness, and 3 （3/18） patients showed cerebellar dysfunction. One patient with LE had progressive motor and sensory polyneuropathy. Lung cancer was detected in 6 （6/18） patients. Ten （10/18） patients showed abnormality in bilateral or unilateral mediotemporal region on magnetic resonance imaging. Ten （10/18） patients had temporal lobe epileptic activity with or without general slowing on EEG. Seventeen patients received immunotherapy and 15 of them showed neurological improvement. Four patients with lung cancer died within 1-12 months due to neoplastic complications. Conclusions： Our study demonstrates that most Han Chinese patients with anti-GABABR antibody-associated LE have prominent refractory epilepsy and show neurological improvement on immunotherapy. Patients with underlying lung tumor have a relati展开更多
Metastasis is the hallmark of cancer that is responsible for the greatest number of cancer-related deaths.Yet,it remains poorly understood.The continuous evolution of cancer biology research and the emergence of new p...Metastasis is the hallmark of cancer that is responsible for the greatest number of cancer-related deaths.Yet,it remains poorly understood.The continuous evolution of cancer biology research and the emergence of new paradigms in the study of metastasis have revealed some of the molecular underpinnings of this dissemination process.The invading tumor cell,on its way to the target site,interacts with other proteins and cells.Recognition of these interactions improved the understanding of some of the biological principles of the metastatic cell that govern its mobility and plasticity.Communication with the tumor microenvironment allows invading cancer cells to overcome stromal challenges,settle,and colonize.These characteristics of cancer cells are driven by genetic and epigenetic modifications within the tumor cell itself and its microenvironment.Establishing the biological mechanisms of the metastatic process is crucial in finding open therapeutic windows for successful interventions.In this review,the authors explore the recent advancements in the field of metastasis and highlight the latest insights that contribute to shaping this hallmark of cancer.展开更多
Neural stem cells （NSCs） are present not only during the embryonic development but also in the adult brain of all mammalian species, including humans. Stem cell niche architecture in vivo enables adult NSCs to conti...Neural stem cells （NSCs） are present not only during the embryonic development but also in the adult brain of all mammalian species, including humans. Stem cell niche architecture in vivo enables adult NSCs to continuously generate functional neurons in specific brain regions throughout life. The adult neurogenesis process is subject to dynamic regulation by various physiological, pathological and pharmacological stimuli. Multipotent adult NSCs also appear to be intrinsically plastic, amenable to genetic programing during normal differentiation, and to epigenetic reprograming during de-differentiation into pluripotency. Increasing evidence suggests that adult NSCs significantly contribute to specialized neural functions under physiological and pathological conditions. Fully understanding the biology of adult NSCs will provide crucial insights into both the etiology and potential therapeutic interventions of major brain disorders. Here, we review recent progress on adult NSCs of the mammalian central nervous system, including topics on their identity, niche, function, plasticity, and emerging roles in cancer and regenerative medicine.展开更多
The homeostasis of the immune system depends on the balance between the immune response to an invaded pathogen and the immune tolerance to self antigens. Both central and peripheral tolerances are important mechanisms...The homeostasis of the immune system depends on the balance between the immune response to an invaded pathogen and the immune tolerance to self antigens. Both central and peripheral tolerances are important mechanisms for the induction and maintenance of T cell tolerance. Recently, much attention has been paid to regulatory T cells （Treg）, which play a significant role in maintaining peripheral immune tolerance. So far, there has been no satisfactory advance regarding the surface markers of Treg cells, as none is unique for Treg cells. In this review, we summarize some important molecules expressed in naturally occurring CD4^＋CD25^＋ Treg cells （nTreg）, including forkhead/winged-helix family transcriptional repressor p3 （Foxp3）, the tumor necrosis factor receptor （TNFR） family, CD28/CTLA4 molecules, chemokine receptors, Toll-like receptors （TLRs）, membrane- bound TGF-β and other molecules, such as neuropilin-1, lymphocyte activation gene-3 （LAG）-3 and granzyme. This review provides a collective view on current studies of nTreg cell activation and development related to the expression of molecules and cell phenotype markers, which is important for elucidation of nTreg cell origin, development and function. Cellular ＆ Molecular Immunology. 2006;3（3）：189-195.展开更多
Gastrodin, the major component isolated from the rhizome of the Chinese traditional medicinal herb Gastrodia elata（‘‘Tianma＇＇）, has a long history in the treatment of epilepsy and other neurological disorders.Ho...Gastrodin, the major component isolated from the rhizome of the Chinese traditional medicinal herb Gastrodia elata（‘‘Tianma＇＇）, has a long history in the treatment of epilepsy and other neurological disorders.However, the molecular mechanisms are not clear. Here,we found that gastrodin ameliorated pentylenetetrazole（PTZ）-induced epileptic seizures with improvement of the electroencephalographic pattern in mice. Further studies demonstrated that gastrodin decreased the levels of the pro-inflammatory cytokines interleukin-1b and tumor necrosis factor-a while increasing interleukin-10, an antiinflammatory cytokine in the brain. Furthermore, gastrodin attenuated the PTZ-induced microglial activation along with inhibition of mitogen-activated protein kinases,c AMP response element binding protein, and NF-j B. Our data suggest that gastrodin attenuates seizures by modulating the mitogen-activated protein kinase-associated inflammatory responses.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
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
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
目的探讨骨质疏松性骨折人群的骨密度与跌倒风险、体质量指数(body mass index,BMI)、肌力、体脂含量的相关性。方法通过对4 632例社区45岁以上绝经后女性的问卷调研及骨密度筛查,筛查出既往有脆性骨折史的骨质疏松性骨折人群。测定骨...目的探讨骨质疏松性骨折人群的骨密度与跌倒风险、体质量指数(body mass index,BMI)、肌力、体脂含量的相关性。方法通过对4 632例社区45岁以上绝经后女性的问卷调研及骨密度筛查,筛查出既往有脆性骨折史的骨质疏松性骨折人群。测定骨质疏松性骨折人群的骨密度、身高、体质量、跌倒风险、肌力和腹部脂肪含量。采用Spearman检验分析跌倒指数、体脂含量、年龄、身高、体质量、BMI与骨密度(bone mass density,BMD)之间的相关性。BMD校正年龄、身高、体质量、BMI、体脂含量,采用ANCOVA分析跌倒指数对BMD的影响;校正年龄、身高、体质量、BMI、跌倒指数,分析体脂含量对BMD的影响。结果对筛查出的839例骨质疏松性骨折患者的BMD、BMI、跌倒风险、腹部体脂含量、肌力等相关性分析结果显示,骨质疏松性骨折人群BMI、跌倒指数、肌力与BMD均显著相关(BMI r=0.161,跌倒指数r=0.238,肌力r=0.198,P均<0.001)。BMI、肌力、跌倒风险与BMD呈正相关;校正年龄、身高、体质量、BMI等因素,采用ANCOVA分析跌倒指数与BMD无显著相关(F=1.011,P>0.05)。结论跌倒风险和低BMD为骨折的主要危险因素。本研究显示体脂含量与BMD呈显著相关性。展开更多
Parkinson’s disease(PD),the second most common age-associated neurodegenerative disorder,is characterized by the loss of dopaminergic(DA)neurons and the presence ofα-synuclein-containing aggregates in the substantia...Parkinson’s disease(PD),the second most common age-associated neurodegenerative disorder,is characterized by the loss of dopaminergic(DA)neurons and the presence ofα-synuclein-containing aggregates in the substantia nigra pars compacta(SNpc).Chronic neuroinflammation is one of the hallmarks of PD pathophysiology.Postmortem analyses of human PD patients and experimental animal studies indicate that activation of glial cells and increases in pro-inflammatory factor levels are common features of the PD brain.Chronic release of proinflammatory cytokines by activated astrocytes and microglia leads to the exacerbation of DA neuron degeneration in the SNpc.Besides,peripheral immune system is also implicated in the pathogenesis of PD.Infiltration and accumulation of immune cells from the periphery are detected in and around the affected brain regions of PD patients.Moreover,inflammatory processes have been suggested as promising interventional targets for PD and even other neurodegenerative diseases.A better understanding of the role of inflammation in PD will provide new insights into the pathological processes and help to establish effective therapeutic strategies.In this review,we will summarize recent progresses in the neuroimmune aspects of PD and highlight the potential therapeutic interventions targeting neuroinflammation.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
Glial scarring following severe tissue damage and inflammation after spinal cord injury （SCI） is due to an extreme, uncontrolled form of reactive astrogliosis that typically occurs around the injury site. The scarri...Glial scarring following severe tissue damage and inflammation after spinal cord injury （SCI） is due to an extreme, uncontrolled form of reactive astrogliosis that typically occurs around the injury site. The scarring process includes the misalignment of activated astrocytes and the deposition of inhibitory chondroitin sulfate proteoglycans. Here, we first discuss recent developments in the molecular and cellular features of glial scar formation, with special focus on the potential cellular origin of scar-forming cells and the molecular mechanisms underlying glial scar formation after SCI. Second, we discuss the role of glial scar formation in the regulation of axonal regeneration and the cascades of neuro-inflammation. Last, we summarize the physical and pharmacological approaches targeting the modulation of glial scarring to better understand the role of glial scar formation in the repair of SCI.展开更多
Brain-derived neurotrophic factor(BDNF) attracts increasing attention from both research and clinical fields because of its important functions in the central nervous system. An adequate amount of BDNF is critical to ...Brain-derived neurotrophic factor(BDNF) attracts increasing attention from both research and clinical fields because of its important functions in the central nervous system. An adequate amount of BDNF is critical to develop and maintain normal neuronal circuits in the brain. Given that loss of BDNF function has beenreported in the brains of patients with neurodegenerative or psychiatric diseases, understanding basic properties of BDNF and associated intracellular processes is imperative. In this review, we revisit the gene structure, transcription, translation, transport and secretion mechanisms of BDNF. We also introduce implications of BDNF in several brain-related diseases including Alzheimer's disease, Huntington's disease, depression and schizophrenia.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.
基金supported by the Foundation for Science and Technology Research Project of Chongqing(cstc2012ggB1002).
文摘Ischemic stroke is a common disease with high mortality and morbidity worldwide.One of the important pathophysiological effects of ischemic stroke is apoptosis.A neuroprotective effect is defined as the inhibition of neuronal apoptosis to rescue or delay the infarction in the surviving ischemic penumbra.Resveratrol is a natural polyphenol that reportedly prevents cerebral ischemia injury by regulating the expression of PI3K/AKT/mTOR.Therefore,this study aimed to elucidate the neuroprotective effect of resveratrol on cerebral ischemia/reperfusion injury and to investigate the signaling pathways and mechanisms through which resveratrol regulates apoptosis in the ischemic penumbra.Rats were subjected to middle cerebral artery occlusion for 2 h followed by 24 h reperfusion.Cerebral infarct volume was measured using 2%TTC staining.TUNEL staining was conducted to evaluate neuronal apoptosis.Western blotting and immunohistochemistry were used to detect the proteins involved in the JAK2/STAT3/PI3K/AKT/mTOR pathway.The results suggested that resveratrol significantly improved neurological function,reduced cerebral infarct volume,decreased neuronal damage,and markedly attenuated neuronal apoptosis;these effects were attenuated by the inhibition of PI3K/AKT with LY294002 and JAK2/STAT3 with AG490.We also found that resveratrol significantly upregulated the expression of p-JAK2,p-STAT3,p-AKT,p-mTOR,and BCL-2 and downregulated expression of cleaved caspase-3 and BAX,which was partially reversed by LY294002 and AG490.These results suggested that resveratrol provides a neuroprotective effect against cerebral ischemia/reperfusion injury,which is partially mediated by the activation of JAK2/STAT3 and PI3K/AKT/mTOR.Resveratrol may indirectly upregulate the PI3K/AKT/mTOR pathway by activating JAK2/STAT3.
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Supported by funds from the Ministry of Science and Technology of China(2018YFC1312300)The National Natural Science Foundation of China(81722016,82071191)The Alzheimer’s Association(AARFD-16-442821).
文摘Ferroptosis is an iron-dependent cell death,which is different from apoptosis,necrosis,autophagy,and other forms of cell death.The process of feroptotic cell death is defined by the accumulation of lethal lipid species derived from the peroxidation of lipids,which can be prevented by iron chelators(e.g.deferiprone,deferoxamine)and small lipophilic antioxidants(e.g,ferrostatin,liproxstatin).This review summarizes current knowledge about the regulatory mechanism of ferroptosis and its association withseveral pathways,including iron,lipid,and cysteine metabolism.We have further discussed the contribution of ferroptosis to thepathogenesis of several diseases such as cancer,ischemia/reperfusion,and various neurodegenerative diseases(e.g.Alzheimersdisease and Parkinson's disease),and evaluated the therapeutic applications of ferroptosis inhibitors in clinics.
基金supported by a grant from the National Institutes of Health HD072968Agriculture and Food Research Initiative Competitive Grant No. 2017-67015-26673 from the USDA National Institute of Food and Agriculture
文摘The gastrointestinal(GI) barrier serves a critical role in survival and overall health of animals and humans. Several layers of barrier defense mechanisms are provided by the epithelial, immune and enteric nervous systems. Together they act in concert to control normal gut functions(e.g., digestion,absorption, secretion, immunity, etc.) whereas at the same time provide a barrier from the hostile conditions in the luminal environment. Breakdown of these critical GI functions is a central pathophysiological mechanism in the most serious GI disorders in pigs. This review will focus on the development and functional properties of the GI barrier in pigs and how common early life production stressors, such as weaning, can alter immediate and long-term barrier function and disease susceptibility.Specific stress-related pathophysiological mechanisms responsible for driving GI barrier dysfunction induced by weaning and the implications to animal health and performance will be discussed.
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Background： Autoimmune encephalitis associated with antibodies against γ-aminobutyric acid B receptor （GABABR） in patients with limbic encephalitis （LE） was first described in 2010. We present a series of klan Chinese patients tbr further clinical refinement. Methods： Serum and cerebrospinal fluid （CSF） samples from patients referred to the program of encephalitis and paraneoplastic syndrome of Peking Union Medical College Hospital were tested with indirect immunofluorescence. Clinical information of patients with anti-GABABR antibody positivity was retrospectively reviewed, and descriptive statistical analysis was performed. Results： All eighteen anti-GABABR antibody-positive cases had limbic syndromes, and electroencephalogram （EEG） or neuroimaging evidence fulfilled the diagnostic criteria of LE. Four patients had additional antibodies against Hu in serum and one had anti-N-methyl-d-aspartate receptor antibody in both sera and CSF. Seventeen （17/18） patients presented with new-onset refractory seizure or status epileptics. Twelve （12/18） patients had memory deficits, 11 （11/18） patients had personality change, 7 （7/18） patients had disturbance of consciousness, and 3 （3/18） patients showed cerebellar dysfunction. One patient with LE had progressive motor and sensory polyneuropathy. Lung cancer was detected in 6 （6/18） patients. Ten （10/18） patients showed abnormality in bilateral or unilateral mediotemporal region on magnetic resonance imaging. Ten （10/18） patients had temporal lobe epileptic activity with or without general slowing on EEG. Seventeen patients received immunotherapy and 15 of them showed neurological improvement. Four patients with lung cancer died within 1-12 months due to neoplastic complications. Conclusions： Our study demonstrates that most Han Chinese patients with anti-GABABR antibody-associated LE have prominent refractory epilepsy and show neurological improvement on immunotherapy. Patients with underlying lung tumor have a relati
文摘Metastasis is the hallmark of cancer that is responsible for the greatest number of cancer-related deaths.Yet,it remains poorly understood.The continuous evolution of cancer biology research and the emergence of new paradigms in the study of metastasis have revealed some of the molecular underpinnings of this dissemination process.The invading tumor cell,on its way to the target site,interacts with other proteins and cells.Recognition of these interactions improved the understanding of some of the biological principles of the metastatic cell that govern its mobility and plasticity.Communication with the tumor microenvironment allows invading cancer cells to overcome stromal challenges,settle,and colonize.These characteristics of cancer cells are driven by genetic and epigenetic modifications within the tumor cell itself and its microenvironment.Establishing the biological mechanisms of the metastatic process is crucial in finding open therapeutic windows for successful interventions.In this review,the authors explore the recent advancements in the field of metastasis and highlight the latest insights that contribute to shaping this hallmark of cancer.
文摘Neural stem cells （NSCs） are present not only during the embryonic development but also in the adult brain of all mammalian species, including humans. Stem cell niche architecture in vivo enables adult NSCs to continuously generate functional neurons in specific brain regions throughout life. The adult neurogenesis process is subject to dynamic regulation by various physiological, pathological and pharmacological stimuli. Multipotent adult NSCs also appear to be intrinsically plastic, amenable to genetic programing during normal differentiation, and to epigenetic reprograming during de-differentiation into pluripotency. Increasing evidence suggests that adult NSCs significantly contribute to specialized neural functions under physiological and pathological conditions. Fully understanding the biology of adult NSCs will provide crucial insights into both the etiology and potential therapeutic interventions of major brain disorders. Here, we review recent progress on adult NSCs of the mammalian central nervous system, including topics on their identity, niche, function, plasticity, and emerging roles in cancer and regenerative medicine.
基金This work was supported by grants from the National Natural Science Foundation for Distinguished Young Scholars(C03020504,Y.Z.)the National Basic Research Program(973 Program,2003CB515501,Y.Z.)+2 种基金100 Quality Vocational Colleges of Chinese Academy of Sciences(2003-85,Y.Z.)the Knowledge Innovation Program of Chinese Academy of Sciences(KSCX2-SW-333,Y.Z.)the Scientific Research Foundation for the Returned 0verseas Chinese Scholars of State Education Ministry(2005-546,Y.Z.).
文摘The homeostasis of the immune system depends on the balance between the immune response to an invaded pathogen and the immune tolerance to self antigens. Both central and peripheral tolerances are important mechanisms for the induction and maintenance of T cell tolerance. Recently, much attention has been paid to regulatory T cells （Treg）, which play a significant role in maintaining peripheral immune tolerance. So far, there has been no satisfactory advance regarding the surface markers of Treg cells, as none is unique for Treg cells. In this review, we summarize some important molecules expressed in naturally occurring CD4^＋CD25^＋ Treg cells （nTreg）, including forkhead/winged-helix family transcriptional repressor p3 （Foxp3）, the tumor necrosis factor receptor （TNFR） family, CD28/CTLA4 molecules, chemokine receptors, Toll-like receptors （TLRs）, membrane- bound TGF-β and other molecules, such as neuropilin-1, lymphocyte activation gene-3 （LAG）-3 and granzyme. This review provides a collective view on current studies of nTreg cell activation and development related to the expression of molecules and cell phenotype markers, which is important for elucidation of nTreg cell origin, development and function. Cellular ＆ Molecular Immunology. 2006;3（3）：189-195.
文摘Gastrodin, the major component isolated from the rhizome of the Chinese traditional medicinal herb Gastrodia elata（‘‘Tianma＇＇）, has a long history in the treatment of epilepsy and other neurological disorders.However, the molecular mechanisms are not clear. Here,we found that gastrodin ameliorated pentylenetetrazole（PTZ）-induced epileptic seizures with improvement of the electroencephalographic pattern in mice. Further studies demonstrated that gastrodin decreased the levels of the pro-inflammatory cytokines interleukin-1b and tumor necrosis factor-a while increasing interleukin-10, an antiinflammatory cytokine in the brain. Furthermore, gastrodin attenuated the PTZ-induced microglial activation along with inhibition of mitogen-activated protein kinases,c AMP response element binding protein, and NF-j B. Our data suggest that gastrodin attenuates seizures by modulating the mitogen-activated protein kinase-associated inflammatory responses.
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.
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.
文摘目的探讨骨质疏松性骨折人群的骨密度与跌倒风险、体质量指数(body mass index,BMI)、肌力、体脂含量的相关性。方法通过对4 632例社区45岁以上绝经后女性的问卷调研及骨密度筛查,筛查出既往有脆性骨折史的骨质疏松性骨折人群。测定骨质疏松性骨折人群的骨密度、身高、体质量、跌倒风险、肌力和腹部脂肪含量。采用Spearman检验分析跌倒指数、体脂含量、年龄、身高、体质量、BMI与骨密度(bone mass density,BMD)之间的相关性。BMD校正年龄、身高、体质量、BMI、体脂含量,采用ANCOVA分析跌倒指数对BMD的影响;校正年龄、身高、体质量、BMI、跌倒指数,分析体脂含量对BMD的影响。结果对筛查出的839例骨质疏松性骨折患者的BMD、BMI、跌倒风险、腹部体脂含量、肌力等相关性分析结果显示,骨质疏松性骨折人群BMI、跌倒指数、肌力与BMD均显著相关(BMI r=0.161,跌倒指数r=0.238,肌力r=0.198,P均<0.001)。BMI、肌力、跌倒风险与BMD呈正相关;校正年龄、身高、体质量、BMI等因素,采用ANCOVA分析跌倒指数与BMD无显著相关(F=1.011,P>0.05)。结论跌倒风险和低BMD为骨折的主要危险因素。本研究显示体脂含量与BMD呈显著相关性。
基金by grants from the National Key Basic Research Program of China(2011CB504102)Natural Science Foundation of China(31430036,31123002,31321091).
文摘Parkinson’s disease(PD),the second most common age-associated neurodegenerative disorder,is characterized by the loss of dopaminergic(DA)neurons and the presence ofα-synuclein-containing aggregates in the substantia nigra pars compacta(SNpc).Chronic neuroinflammation is one of the hallmarks of PD pathophysiology.Postmortem analyses of human PD patients and experimental animal studies indicate that activation of glial cells and increases in pro-inflammatory factor levels are common features of the PD brain.Chronic release of proinflammatory cytokines by activated astrocytes and microglia leads to the exacerbation of DA neuron degeneration in the SNpc.Besides,peripheral immune system is also implicated in the pathogenesis of PD.Infiltration and accumulation of immune cells from the periphery are detected in and around the affected brain regions of PD patients.Moreover,inflammatory processes have been suggested as promising interventional targets for PD and even other neurodegenerative diseases.A better understanding of the role of inflammation in PD will provide new insights into the pathological processes and help to establish effective therapeutic strategies.In this review,we will summarize recent progresses in the neuroimmune aspects of PD and highlight the potential therapeutic interventions targeting neuroinflammation.
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.
基金supported by grants from the National Basic Research Development Program of China (2011CB504401)the National Natural Science Foundation of China (31130024,31070922 and 81261130313)
文摘Glial scarring following severe tissue damage and inflammation after spinal cord injury （SCI） is due to an extreme, uncontrolled form of reactive astrogliosis that typically occurs around the injury site. The scarring process includes the misalignment of activated astrocytes and the deposition of inhibitory chondroitin sulfate proteoglycans. Here, we first discuss recent developments in the molecular and cellular features of glial scar formation, with special focus on the potential cellular origin of scar-forming cells and the molecular mechanisms underlying glial scar formation after SCI. Second, we discuss the role of glial scar formation in the regulation of axonal regeneration and the cascades of neuro-inflammation. Last, we summarize the physical and pharmacological approaches targeting the modulation of glial scarring to better understand the role of glial scar formation in the repair of SCI.
基金Supported by The Health and Labor Sciences Research Grants(Comprehensive Research on Disability,Health,and Welfare H21-kokoro-002)(H.K.)the Core Research for Evolutional Science and Technology Program,CREST,Japan Science and Technology Agency(JST)(T.N.,N.A.and H.K.)+3 种基金the Naito Foundation(N.A)the Takeda Science Foundation(T.N.)a grant from Grant-in-Aid for Scientific Research(B),(JSPS KAKENHI)(T.N.),No.24300139Grant-in-Aid for Challenging Exploratory Research(JSPS KAKENHI)(T.N.)from the Ministry of Education,Culture,Sports,Science,and Technology of Japan,No.25640019
文摘Brain-derived neurotrophic factor(BDNF) attracts increasing attention from both research and clinical fields because of its important functions in the central nervous system. An adequate amount of BDNF is critical to develop and maintain normal neuronal circuits in the brain. Given that loss of BDNF function has beenreported in the brains of patients with neurodegenerative or psychiatric diseases, understanding basic properties of BDNF and associated intracellular processes is imperative. In this review, we revisit the gene structure, transcription, translation, transport and secretion mechanisms of BDNF. We also introduce implications of BDNF in several brain-related diseases including Alzheimer's disease, Huntington's disease, depression and schizophrenia.
