Oxidative stress plays a significant role in the pathogenesis of Alzheimer＇s disease （AD）, a devastating disease of the elderly. The brain is more vulnerable than other organs to oxidative stress, and most of the c...Oxidative stress plays a significant role in the pathogenesis of Alzheimer＇s disease （AD）, a devastating disease of the elderly. The brain is more vulnerable than other organs to oxidative stress, and most of the components of neurons （lipids, proteins, and nucleic acids） can be oxidized in AD due to mitochondrial dysfunction, increased metal levels, inflammation, and β-amyloid （Aβ） peptides. Oxidative stress participates in the development of AD by promoting Aβ deposition, tau hyperphosphorylation, and the subsequent loss of synapses and neurons. The relationship between oxidative stress and AD suggests that oxidative stress is an essential part of the pathological process, and antioxidants may be useful for AD treatment.展开更多
Objective：To systematically review the updated information about the gut microbiota-brain axis.Data Sources：All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literat...Objective：To systematically review the updated information about the gut microbiota-brain axis.Data Sources：All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literature search on PubMed,ScienceDirect,and Web of Science,with the keywords of＂gut microbiota＂,＂gut-brain axis＂,and ＂neuroscience＂.Study Selection：All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed,with no limitation of study design.Results：It is well-recognized that gut microbiota affects the brain＆#39;s physiological,behavioral,and cognitive functions although its precise mechanism has not yet been fully understood.Gut microbiota-brain axis may include gut microbiota and their metabolic products,enteric nervous system,sympathetic and parasympathetic branches within the autonomic nervous system,neural-immune system,neuroendocrine system,and central nervous system.Moreover,there may be five communication routes between gut microbiota and brain,including the gut-brain＆#39;s neural network,neuroendocrine-hypothalamic-pituitary-adrenal axis,gut immune system,some neurotransmitters and neural regulators synthesized by gut bacteria,and barrier paths including intestinal mucosal barrier and blood-brain barrier.The microbiome is used to define the composition and functional characteristics of gut microbiota,and metagenomics is an appropriate technique to characterize gut microbiota.Conclusions：Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain,which may provide a new way to protect the brain in the near future.展开更多
The number and health burden of Parkinson’s disease increase rapidly in China.It is estimated that China will have nearly half of the Parkinson’s disease population in the world in 2030.In this review,we present an ...The number and health burden of Parkinson’s disease increase rapidly in China.It is estimated that China will have nearly half of the Parkinson’s disease population in the world in 2030.In this review,we present an overview of epidemiology and health economics status of Parkinson’s disease across China and discuss the risk factors of Parkinson’s disease and related complications.From the view of clinical research,we also discuss the current status of clinical trials,diagnostic biomarkers,treatment of Parkinson’s disease,tertiary network and post-occupation education in Chinese Parkinson’s disease clinics.展开更多
Increased microvessel density in the peri-infarct region has been reported and has been correlated with longer survival times in ischemic stroke patients and has improved outcomes in ischemic animal models.This raises...Increased microvessel density in the peri-infarct region has been reported and has been correlated with longer survival times in ischemic stroke patients and has improved outcomes in ischemic animal models.This raises the possibility that enhancement of angiogenesis is one of the strategies to facilitate functional recovery after ischemic stroke.Blood vessels and neuronal cells communicate with each other using various mediators and contribute to the pathophysiology of cerebral ischemia as a unit.In this mini-review,we discuss how angiogenesis might couple with axonal outgrowth/neurogenesis and work for functional recovery after cerebral ischemia.Angiogenesis occurs within 4 to 7 days after cerebral ischemia in the border of the ischemic core and periphery.Post-ischemic angiogenesis may contribute to neuronal remodeling in at least two ways and is thought to contribute to functional recovery.First,new blood vessels that are formed after ischemia are thought to have a role in the guidance of sprouting axons by vascular endothelial growth factor and laminin/β1-integrin signaling.Second,blood vessels are thought to enhance neurogenesis in three stages:1)Blood vessels enhance proliferation of neural stem/progenitor cells by expression of several extracellular signals,2)microvessels support the migration of neural stem/progenitor cells toward the peri-infarct region by supplying oxygen,nutrients,and soluble factors as well as serving as a scaffold for migration,and 3)oxygenation induced by angiogenesis in the ischemic core is thought to facilitate the differentiation of migrated neural stem/progenitor cells into mature neurons.Thus,the regions of angiogenesis and surrounding tissue may be coupled,representing novel treatment targets.展开更多
Background and purpose Stroke is the leading cause of mortality and disability in China.Precise aetiological classification,imaging and biological markers may predict the prognosis of stroke.The Third China National S...Background and purpose Stroke is the leading cause of mortality and disability in China.Precise aetiological classification,imaging and biological markers may predict the prognosis of stroke.The Third China National Stroke Registry(CNSR-Ⅲ),a nationwide registry of ischaemic stroke or transient ischaemic attack(TIA)in China based on aetiology,imaging and biology markers,will be considered to clarify the pathogenesis and prognostic factors of ischaemic stroke.Methods Between August 2015 and March 2018,the CNSR-Ⅲrecruited consecutive patients with ischaemic stroke or TIA from 201 hospitals that cover 22 provinces and four municipalities in China.Clinical data were collected prospectively using an electronic data capture system by face-to-face interviews.Patients were followed for clinical outcomes at 3 months,6 months and 1-5 year annually.Brain imaging,including brain MRI and CT,were completed at baseline.Blood samples were collected and biomarkers were tested at baseline.Results A total of 15166 stroke patients were enrolled,among which 31.7%patients were women with the average age of 62.2±11.3 years.Ischaemic stroke was predominant(93.3%,n=14146)and 1020(6.7%)TIAs were enrolled.Conclusions CNSR-Ⅲis a large scale nationwide registry in China.Data from this prospective registry may provide opportunity to evaluate imaging and biomarker prognostic determinants of stroke.展开更多
Wilson＇s disease（WD） is an autosomal recessive disorder of copper metabolism. Its incidence is higher in China than in western countries. ATP7 B is the causative gene and encodes a P-type ATPase, which participates...Wilson＇s disease（WD） is an autosomal recessive disorder of copper metabolism. Its incidence is higher in China than in western countries. ATP7 B is the causative gene and encodes a P-type ATPase, which participates in the synthesis of holoceruloplasmin and copper excretion. Disease-causing variants of ATP7 B disrupt the normal structure or function of the enzyme and cause copper deposition in multiple organs,leading to diverse clinical manifestations. Given the variety of presentations, misdiagnosis is not rare. Genetic diagnosis plays an important role and has gradually become a routine test in China. The first Chinese spectrum of disease-causing mutations of ATP7 B has been established. As a remediable hereditary disorder, most WD patients have a good prognosis with an early diagnosis and chelation treatment. However, clinical trials are relatively few in China, and most treatments are based on the experience of experts and evidences from other countries. It is necessary to study and develop appropriate regimens specific for Chinese WD patients.展开更多
Introduction There is a downward trend of stroke-related mortality in the USA.By reviewing all published articles on stroke mortality in China,we analysed its trend and possible factors that have influenced the trend....Introduction There is a downward trend of stroke-related mortality in the USA.By reviewing all published articles on stroke mortality in China,we analysed its trend and possible factors that have influenced the trend.Methods Both English and Chinese literatures were searched on the mortality of stroke or cerebrovascular diseases in China.Potential papers related to this topic were identified from PubMed,Medline,Embase,Cochrane Library,Wanfang Database,SINOMED and China National Knowledge Infrastructure databases.Results Comparing the results from the most recent population-based epidemiological survey and databank from the national Center for Disease Control and Prevention,the age-adjusted stroke mortality rate has shown a downward trend among both urban and rural population in the past 30 years in China.Comparing with 30 years ago,the rate of stroke mortality has decreased by more than 31%in urban/suburban population and 11%in rural population.In men,the age-adjusted stroke mortality rate decreased by 18.9%and in women by 24.9%between 1994 and 2013.Factors that may have contributed to the trend of decreased stroke mortality rate include(1)improved healthcare coverage and healthcare environment;(2)improved treatment options and medical technology;(3)support by government to educate the public on stroke and stroke prevention;and(4)improved public knowledge on stroke.Conclusions The age-adjusted stroke mortality rate in China has shown a downward trend among both urban and rural population in the past 30 years.The major influencing factors that helped in reducing stroke mortality in China included improved healthcare coverage,healthcare environment,the updated treatment options and modern medical technology.展开更多
Objective Insomnia is a highly prevalent disorder among patients suffering from stroke.The association between insomnia and stroke mortality is less studied,particularly using the latest diagnostic criteria.The curren...Objective Insomnia is a highly prevalent disorder among patients suffering from stroke.The association between insomnia and stroke mortality is less studied,particularly using the latest diagnostic criteria.The current study examined the relationship between insomnia and mortality among patients with first-evonal hazard models were used to calculate HRs for stroke er stroke in China.Methods Patients with acute cerebrovascular diseases(stroke)were recruited from 56 hospitals in China's Mainland.Insomnia was defined as difficulty falling asleep,or difficulty staying asleep or waking up early,for at least two consecutive visits.Demographic data,medical history and clinical data were collected.Four follow-up visits occurred within the first year after stroke,and the last follow-up call was conducted 6 years later.Cox proportional hazard models were used to calculate HRs for stroke mortality.results Insomnia was reported by 38.4%(489/1273)of patients at baseline.During the 6 years of follow-up,after adjusting for all confounders,insomnia was found to be associated with increased mortality(HR=1.66,95%CI 1.10 to 2.48).Old age(HR=1.08,95%CI 1.06 to 1.10),stroke recurrence in the first year of follow-up(HR=2.53,95%CI 1.48 to 4.31)and stroke survivors with hypertension(HR=1.62,95%CI 1.04 to 2.53)had substantially higher risk of mortality.Conclusions Besides old age,stroke recurrence in the first year of follow-up and hypertension,insomnia is associated with increased risk of mortality in patients with first-ever stroke in China.More studies about prompt and efficient interventions for insomnia are expected in the future.Trial registration number rctn62169508.展开更多
Gliomas are the most common and malignant intracranial tumors in adults.Recent studies have revealed the significance of functional genomics for glioma pathophysiological studies and treatments.However,access to compr...Gliomas are the most common and malignant intracranial tumors in adults.Recent studies have revealed the significance of functional genomics for glioma pathophysiological studies and treatments.However,access to comprehensive genomic data and analytical platforms is often limited.Here,we developed the Chinese Glioma Genome Atlas(CGGA),a user-friendly data portal for the storage and interactive exploration of cross-omics data,including nearly 2000 primary and recurrent glioma samples from Chinese cohort.Currently,open access is provided to whole-exome sequencing data(286 samples),mRNA sequencing(1018 samples)and microarray data(301 samples),DNA methylation microarray data(159 samples),and microRNA microarray data(198 samples),and to detailed clinical information(age,gender,chemoradiotherapy status,WHO grade,histological type,critical molecular pathological information,and survival data).In addition,we have developed several tools for users to analyze the mutation profiles,mRNA/microRNA expression,and DNA methylation profiles,and to perform survival and gene correlation analyses of specific glioma subtypes.This database removes the barriers for researchers,providing rapid and convenient access to high-quality functional genomic data resources for biological studies and clinical applications.CGGA is available at http://www.cgga.org.cn.展开更多
Major depressive disorder(MDD)is a prevalent psychiatric disease that involves malfunctions of different cell types in the brain.Accumulating studies started to reveal that microglia,the primary resident immune cells,...Major depressive disorder(MDD)is a prevalent psychiatric disease that involves malfunctions of different cell types in the brain.Accumulating studies started to reveal that microglia,the primary resident immune cells,play an important role in the development and progression of depression.Microglia respond to stress-triggered neuroinflammation,and through the release of proinflammatory cytokines and their metabolic products,microglia may modulate the function of neurons and astrocytes to regulate depression.In this review,we focused on the role of microglia in the etiology of depression.We discussed the dynamic states of microglia;the correlative and causal evidence of microglial abnormalities in depression;possible mechanisms of how microglia sense depression-related stress and modulate depression state;and how antidepressive therapies affect microglia.Understanding the role of microglia in depression may shed light on developing new treatment strategies to fight against this devastating mental illness.展开更多
Spinal cord injury(SCI)remains a severe condition with an extremely high disability rate.The challenges of SCI repair include its complex pathological mechanisms and the difficulties of neural regeneration in the cent...Spinal cord injury(SCI)remains a severe condition with an extremely high disability rate.The challenges of SCI repair include its complex pathological mechanisms and the difficulties of neural regeneration in the central nervous system.In the past few decades,researchers have attempted to completely elucidate the pathological mechanism of SCI and identify effective strategies to promote axon regeneration and neural circuit remodeling.展开更多
Background In June 2015,the Chinese Stroke Association(CSA)initiated the Chinese Stroke Center Alliance(CSCA)to establish the national hospital-based stroke care quality assessment and improvement platform.This articl...Background In June 2015,the Chinese Stroke Association(CSA)initiated the Chinese Stroke Center Alliance(CSCA)to establish the national hospital-based stroke care quality assessment and improvement platform.This article outlines its objectives,operational structure,patient population,quality improvement(QI)intervention tools,data elements,data collection methodology and current patient and hospital data.Methods The CSCA is a national,hospital-based,multicentre,voluntary,multifaceted intervention and continuous QI initiative.This multifaceted intervention includes stroke centre development,written care protocols,workshops and a monitoring/feedback system of evidencebased performance measures.The data coordinating centre of the CSCA resides at the China National Clinical Research Center for Neurological Diseases,Beijing Tiantan Hospital.results As of July 2017,1576 hospitals in China have contributed detailed clinical information to serve as a benchmark for the stroke care quality of 433264 patients with acute stroke/transient ischaemic attacks(TIA),including 352572(81.38%)acute ischaemic stroke,30362(7.01%)TIA,42080(9.71%)spontaneous intracranial haemorrhage,5505(1.27%)subarachnoid haemorrhage and 2745(0.63%)not specified stroke.Conclusion The CSCA programme is designed to establish a continuous national stroke registry and help healthcare providers develop stroke centres and treat patients in a consistent manner in accordance with accepted national guidelines and,ultimately,improve patient outcomes.It supports the CSA mission to reduce stroke burden in China.展开更多
Understanding of the differentiation profile of brain tumor stem cells （BTSCs）, the key ones among tumor cell population, through comparison with neural stem cells （NSCs） would lend insight into the origin of glio...Understanding of the differentiation profile of brain tumor stem cells （BTSCs）, the key ones among tumor cell population, through comparison with neural stem cells （NSCs） would lend insight into the origin of glioma and ultimately yield new approaches to fight this intractable disease. Here, we cultured and purified BTSCs from surgical glioma specimens and NSCs from human fetal brain tissue, and further analyzed their cellular biological behaviors, especially their differentiation property. As expected, NSCs differentiated into mature neural phenotypes. In the same differentiation condition, however, BTSCs exhibited distinguished differences. Morphologically, cells grew flattened and attached for the first week, but gradually aggregated and reformed floating tumor sphere thereafter. During the corresponding period, the expression rate of undifferentiated cell marker CD 133 and nestin in BTSCs kept decreasing, but 1 week later, they regained ascending tendency. Interestingly, the differentiated cell markers GFAP and β-tubulinlII showed an expression change inverse to that of undifferentiated cell markers. Taken together, BTSCs were revealed to possess a capacity to resist differentiation, which actually represents the malignant behaviors of glioma.展开更多
background and purpose A multicentre prospective registry study of individually tailored stenting for a patient with symptomatic intracranial atherosclerotic stenosis(ICAS)combined with poor collaterals in China showe...background and purpose A multicentre prospective registry study of individually tailored stenting for a patient with symptomatic intracranial atherosclerotic stenosis(ICAS)combined with poor collaterals in China showed that the short-term safety and efficacy of stenting was acceptable.However,it remained uncertain whether the low event rate could be of a long term.We reported the 1-year outcome of this registry study to evaluate the long-term efficacy of individually tailored stenting for patients with severe symptomatic ICAS combined with poor collaterals.Methods Patients with symptomatic ICAS caused by 70%-99% stenosis located at the intracranial internal carotid,middle cerebral,intracranial vertebral or basilar arteries combined with poor collaterals were enrolled.Balloon-mounted stent or balloon plus self-expanding stent were selected based on the ease of vascular access and lesion morphology determined by the operators.The primary outcome was the rate of 30-day stroke,transient ischaemic attack and death,and 12-month ischaemic stroke within the same vascular territory,haemorrhagic stroke and vascular death after stenting.results From September 2013 to January 2015,300 patients(ages 58.3±9.78 years)were recruited.Among them,159 patients were treated with balloon-mounted stent and 141 with balloon plus self-expanding stent.During the 1-year follow-up,25 patients had a primary end point event.The probability of primary outcome at 1 year was 8.1%(95% CI 5.3% to 11.7%).In 76 patients with digital subtraction angiography follow-up,27.6%(21/76)had re-stenosis≥50% and 18.4%(14/76)had re-stenosis≥70%.No baseline characteristic was associated with the primary outcome.Conclusion The event rate remains low over 1 year of individually tailored stenting for patients with severe symptomatic ICAS combined with poor collaterals.Further randomised trial of comparing individually tailored stenting with best medical therapy is needed.展开更多
Cerebral ischemia is one of the leading causes of morbidity and mortality worldwide. Although stroke （a form of cerebral ischemia）-related costs are expected to reach 240.67 billion dollars by 2030, options for trea...Cerebral ischemia is one of the leading causes of morbidity and mortality worldwide. Although stroke （a form of cerebral ischemia）-related costs are expected to reach 240.67 billion dollars by 2030, options for treatment against cerebral ischemia/stroke are limited. All therapies except anti-thrombolytics （i.e., tissue plasminogen activator） and hypothermia have failed to reduce neuronal injury, neurological deficits, and mortality rates following cerebral ischemia, which suggests that development of novel therapies again st stroke/cerebral ischemia are urgently needed. Here, we discuss the possible mechanism（s） underlying cerebral ischemia-induced brain injury, as well as current and future novel therapies （i.e., growth factors, nicotinamide adenine dinucleotide, melatonin, resveratrol, protein kinase C isozymes, pifithrin, hypothermia, fatty acids, sympathoplegic drugs, and stem cells） as it relates to cerebral ischemia.展开更多
Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human dise...Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human diseases,including cardiovascular disease,diabetes,neurological degeneration,and cancer.Therefore,the growing emphasis on “healthy aging” raises a series of important questions in life and social sciences.In recent years,there has been unprecedented progress in aging research,particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes.In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases,we review the descriptive,conceptual,and interventive aspects of the landscape of aging composed of a number of layers at the cellular,tissue,organ,organ system,and organismal levels.展开更多
Psychological stress is an important factor for the development of irritable bowel syndrome(IBS). More and more clinical and experimental evidence showed that IBS is a combination of irritable bowel and irritable brai...Psychological stress is an important factor for the development of irritable bowel syndrome(IBS). More and more clinical and experimental evidence showed that IBS is a combination of irritable bowel and irritable brain. In the present review we discuss the potential role of psychological stress in the pathogenesis of IBS and provide comprehensive approaches in clinical treatment. Evidence from clinical and experimental studies showed that psychological stresses have marked impact on intestinal sensitivity, motility, secretion and permeability, and the underlying mechanism has a close correlation with mucosal immune activation, alterations in central nervous system, peripheral neurons and gastrointestinal microbiota. Stress-induced alterations in neuro-endocrine-immune pathways acts on the gut-brain axis and microbiota-gut-brain axis, and cause symptom flare-ups or exaggeration in IBS. IBS is a stresssensitive disorder, therefore, the treatment of IBS should focus on managing stress and stress-induced responses. Now, non-pharmacological approaches and pharmacological strategies that target on stress-related alterations, such as antidepressants, antipsychotics, miscellaneous agents, 5-HT synthesis inhibitors, selective 5-HT reuptake inhibitors, and specific 5-HT receptor antagonists or agonists have shown a critical role in IBS management. A integrative approach for IBS management is a necessary.展开更多
Since the outbreak of the coronavirus disease 2019(COVID-19)pandemic,there have been a few variants of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),one of which is the Omicron variant(B.1.1.529).The...Since the outbreak of the coronavirus disease 2019(COVID-19)pandemic,there have been a few variants of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),one of which is the Omicron variant(B.1.1.529).The Omicron variant is the most mutated SARS-CoV-2 variant,and its high transmissibility and immune evasion ability have raised global concerns.Owing to its enhanced transmissibility,Omicron has rapidly replaced Delta as the dominant variant in several regions.However,recent studies have shown that the Omicron variant exhibits reduced pathogenicity due to altered cell tropism.In addition.展开更多
Citrin deficiency,autosomal recessive disorder,caused by mutation of SLC25A13 gene on chromosome 7q21.3 has two major phenotypes:neonatal intrahepatic cholestatic hepatitis(NICCD)and adult-onset type Ⅱ citrullinemia(...Citrin deficiency,autosomal recessive disorder,caused by mutation of SLC25A13 gene on chromosome 7q21.3 has two major phenotypes:neonatal intrahepatic cholestatic hepatitis(NICCD)and adult-onset type Ⅱ citrullinemia(CTLN2).So far,we have identified 52 SLC25A13 mutations and diagnosed the patients not only in Japan(166 CTLN2 and 238 NICCD) but also in other countries.We have detected 76 Chinese,13 Korean and 15 Vietnamese patients with the same mutations as Japanese,and 13 patients(from Israel,UK,USA or Czech)with mutations different from those found in Japanese,indicating a wide distribution of citrin deficiency.DNA diagnoses of 13 known SLC25A13 mutations revealed that the carrier frequency was high in East Asian populations:Chinese(73/4 600=1/63),Japanese(21/1 372=1/65) and Korean(25/2 690=1/108),suggesting that near by 100 000 East Asians are homozygotes.It is important to find out patients with citrin deficiency,to treat them,and to prevent onset of severe CTLN2.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
基金supported by National Basic Research Development Program(973 Program)of China(2011CBA00400)the National Natural Science Foundation of China(91332201)+1 种基金the Natural Science Foundation of Shanghai Municipality,China(13JC1401500)fund for Medical Emerging Cutting-edge Technology in Shanghai Municipality,China(SHDC12012114)
文摘Oxidative stress plays a significant role in the pathogenesis of Alzheimer＇s disease （AD）, a devastating disease of the elderly. The brain is more vulnerable than other organs to oxidative stress, and most of the components of neurons （lipids, proteins, and nucleic acids） can be oxidized in AD due to mitochondrial dysfunction, increased metal levels, inflammation, and β-amyloid （Aβ） peptides. Oxidative stress participates in the development of AD by promoting Aβ deposition, tau hyperphosphorylation, and the subsequent loss of synapses and neurons. The relationship between oxidative stress and AD suggests that oxidative stress is an essential part of the pathological process, and antioxidants may be useful for AD treatment.
基金This study was supported by grants from Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support （No. XMLX201401）, the National Natural Science Foundation of China （No. 81301138）, National High-Tech R＆D Program of China （863 Program, No. 2015AA020514）, National Hundred, Thousand, and Ten Thousand Talents Project of Beijing （No. 2010-005）.
文摘Objective：To systematically review the updated information about the gut microbiota-brain axis.Data Sources：All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literature search on PubMed,ScienceDirect,and Web of Science,with the keywords of＂gut microbiota＂,＂gut-brain axis＂,and ＂neuroscience＂.Study Selection：All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed,with no limitation of study design.Results：It is well-recognized that gut microbiota affects the brain＆#39;s physiological,behavioral,and cognitive functions although its precise mechanism has not yet been fully understood.Gut microbiota-brain axis may include gut microbiota and their metabolic products,enteric nervous system,sympathetic and parasympathetic branches within the autonomic nervous system,neural-immune system,neuroendocrine system,and central nervous system.Moreover,there may be five communication routes between gut microbiota and brain,including the gut-brain＆#39;s neural network,neuroendocrine-hypothalamic-pituitary-adrenal axis,gut immune system,some neurotransmitters and neural regulators synthesized by gut bacteria,and barrier paths including intestinal mucosal barrier and blood-brain barrier.The microbiome is used to define the composition and functional characteristics of gut microbiota,and metagenomics is an appropriate technique to characterize gut microbiota.Conclusions：Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain,which may provide a new way to protect the brain in the near future.
基金This work was supported by grants from the National Natural Science Foundation of China[grant numbers 81430022,91332107,81371407].
文摘The number and health burden of Parkinson’s disease increase rapidly in China.It is estimated that China will have nearly half of the Parkinson’s disease population in the world in 2030.In this review,we present an overview of epidemiology and health economics status of Parkinson’s disease across China and discuss the risk factors of Parkinson’s disease and related complications.From the view of clinical research,we also discuss the current status of clinical trials,diagnostic biomarkers,treatment of Parkinson’s disease,tertiary network and post-occupation education in Chinese Parkinson’s disease clinics.
基金supported by a Grant-in-Aid for Scientific Research(Research Project No.15K19478 and 18K07493,both to MK)Japan Science and Technology Agency(JST),the Translational Research program+7 种基金Strategic Promotion for practical application of Innovative medical Technology(TR-SPRINT)supported by Japan Agency for Medical Research and Development(AMED)under Grant No.JP19lm0203023a grant from Takeda Science Foundationthe Bayer Scholarship for Cardiovascular ResearchJapan Cardiovascular Research FoundationAstellas Foundation for Research on Metabolic DisordersYoung Investigator Okamoto AwardMedical Research Encouragement Prize of the Japan Medical Association(to MK)supported by a grant from Tsubaki Memorial Foundation(to MH and IN)
文摘Increased microvessel density in the peri-infarct region has been reported and has been correlated with longer survival times in ischemic stroke patients and has improved outcomes in ischemic animal models.This raises the possibility that enhancement of angiogenesis is one of the strategies to facilitate functional recovery after ischemic stroke.Blood vessels and neuronal cells communicate with each other using various mediators and contribute to the pathophysiology of cerebral ischemia as a unit.In this mini-review,we discuss how angiogenesis might couple with axonal outgrowth/neurogenesis and work for functional recovery after cerebral ischemia.Angiogenesis occurs within 4 to 7 days after cerebral ischemia in the border of the ischemic core and periphery.Post-ischemic angiogenesis may contribute to neuronal remodeling in at least two ways and is thought to contribute to functional recovery.First,new blood vessels that are formed after ischemia are thought to have a role in the guidance of sprouting axons by vascular endothelial growth factor and laminin/β1-integrin signaling.Second,blood vessels are thought to enhance neurogenesis in three stages:1)Blood vessels enhance proliferation of neural stem/progenitor cells by expression of several extracellular signals,2)microvessels support the migration of neural stem/progenitor cells toward the peri-infarct region by supplying oxygen,nutrients,and soluble factors as well as serving as a scaffold for migration,and 3)oxygenation induced by angiogenesis in the ischemic core is thought to facilitate the differentiation of migrated neural stem/progenitor cells into mature neurons.Thus,the regions of angiogenesis and surrounding tissue may be coupled,representing novel treatment targets.
基金This study was supported by grants from the Ministry of Science and Technology of the People’s Republic of China(2016YFC0901001,2016YFC0901002,2017YFC1310901,2017YFC1310902,2018YFC1311700 and 2018YFC1311706)grants from Beijing Municipal Commission of Health and Family Planning(No.2016-1-2041,SML20150502).
文摘Background and purpose Stroke is the leading cause of mortality and disability in China.Precise aetiological classification,imaging and biological markers may predict the prognosis of stroke.The Third China National Stroke Registry(CNSR-Ⅲ),a nationwide registry of ischaemic stroke or transient ischaemic attack(TIA)in China based on aetiology,imaging and biology markers,will be considered to clarify the pathogenesis and prognostic factors of ischaemic stroke.Methods Between August 2015 and March 2018,the CNSR-Ⅲrecruited consecutive patients with ischaemic stroke or TIA from 201 hospitals that cover 22 provinces and four municipalities in China.Clinical data were collected prospectively using an electronic data capture system by face-to-face interviews.Patients were followed for clinical outcomes at 3 months,6 months and 1-5 year annually.Brain imaging,including brain MRI and CT,were completed at baseline.Blood samples were collected and biomarkers were tested at baseline.Results A total of 15166 stroke patients were enrolled,among which 31.7%patients were women with the average age of 62.2±11.3 years.Ischaemic stroke was predominant(93.3%,n=14146)and 1020(6.7%)TIAs were enrolled.Conclusions CNSR-Ⅲis a large scale nationwide registry in China.Data from this prospective registry may provide opportunity to evaluate imaging and biomarker prognostic determinants of stroke.
基金supported by the National Natural Science Foundation of China(81125009)
文摘Wilson＇s disease（WD） is an autosomal recessive disorder of copper metabolism. Its incidence is higher in China than in western countries. ATP7 B is the causative gene and encodes a P-type ATPase, which participates in the synthesis of holoceruloplasmin and copper excretion. Disease-causing variants of ATP7 B disrupt the normal structure or function of the enzyme and cause copper deposition in multiple organs,leading to diverse clinical manifestations. Given the variety of presentations, misdiagnosis is not rare. Genetic diagnosis plays an important role and has gradually become a routine test in China. The first Chinese spectrum of disease-causing mutations of ATP7 B has been established. As a remediable hereditary disorder, most WD patients have a good prognosis with an early diagnosis and chelation treatment. However, clinical trials are relatively few in China, and most treatments are based on the experience of experts and evidences from other countries. It is necessary to study and develop appropriate regimens specific for Chinese WD patients.
文摘Introduction There is a downward trend of stroke-related mortality in the USA.By reviewing all published articles on stroke mortality in China,we analysed its trend and possible factors that have influenced the trend.Methods Both English and Chinese literatures were searched on the mortality of stroke or cerebrovascular diseases in China.Potential papers related to this topic were identified from PubMed,Medline,Embase,Cochrane Library,Wanfang Database,SINOMED and China National Knowledge Infrastructure databases.Results Comparing the results from the most recent population-based epidemiological survey and databank from the national Center for Disease Control and Prevention,the age-adjusted stroke mortality rate has shown a downward trend among both urban and rural population in the past 30 years in China.Comparing with 30 years ago,the rate of stroke mortality has decreased by more than 31%in urban/suburban population and 11%in rural population.In men,the age-adjusted stroke mortality rate decreased by 18.9%and in women by 24.9%between 1994 and 2013.Factors that may have contributed to the trend of decreased stroke mortality rate include(1)improved healthcare coverage and healthcare environment;(2)improved treatment options and medical technology;(3)support by government to educate the public on stroke and stroke prevention;and(4)improved public knowledge on stroke.Conclusions The age-adjusted stroke mortality rate in China has shown a downward trend among both urban and rural population in the past 30 years.The major influencing factors that helped in reducing stroke mortality in China included improved healthcare coverage,healthcare environment,the updated treatment options and modern medical technology.
基金This study was funded by National Key Research&Development Program of China(2016YFC1307200)Beijing excellent talents training Program,the Ministry of Science and Technology and the Ministry of Health of the People’s Republic of China.Individual grants include the National 11th&12th Five-year S&T Major Project(2006BAI01A11,2011BAI08B01,2011BAI08B02,2015BAI13B03)+5 种基金the National Key Technology Research and Development Program of the Ministry of Science and Technology of China(2013BAI09B03)the Ministry of Science and Technology of the People’s Republic of China Beijing Institute for Brain Disorders(BIBD-PXM2013_014226_07_000084)the Beijing Biobank of Cerebral Vascular Disease(D131100005313003)the Basic Clinical Research Cooperation Program of Capital Medical University(16JL(TTZX)03)Beijing Brain Research(Z161100000216131)the Beijing Municipal Science&Technology Commission(Z151100004015127 and Z151100003915117)。
文摘Objective Insomnia is a highly prevalent disorder among patients suffering from stroke.The association between insomnia and stroke mortality is less studied,particularly using the latest diagnostic criteria.The current study examined the relationship between insomnia and mortality among patients with first-evonal hazard models were used to calculate HRs for stroke er stroke in China.Methods Patients with acute cerebrovascular diseases(stroke)were recruited from 56 hospitals in China's Mainland.Insomnia was defined as difficulty falling asleep,or difficulty staying asleep or waking up early,for at least two consecutive visits.Demographic data,medical history and clinical data were collected.Four follow-up visits occurred within the first year after stroke,and the last follow-up call was conducted 6 years later.Cox proportional hazard models were used to calculate HRs for stroke mortality.results Insomnia was reported by 38.4%(489/1273)of patients at baseline.During the 6 years of follow-up,after adjusting for all confounders,insomnia was found to be associated with increased mortality(HR=1.66,95%CI 1.10 to 2.48).Old age(HR=1.08,95%CI 1.06 to 1.10),stroke recurrence in the first year of follow-up(HR=2.53,95%CI 1.48 to 4.31)and stroke survivors with hypertension(HR=1.62,95%CI 1.04 to 2.53)had substantially higher risk of mortality.Conclusions Besides old age,stroke recurrence in the first year of follow-up and hypertension,insomnia is associated with increased risk of mortality in patients with first-ever stroke in China.More studies about prompt and efficient interventions for insomnia are expected in the future.Trial registration number rctn62169508.
基金supported by the National Natural Science Foundation of China(Grant Nos.81702460 and 81802994)
文摘Gliomas are the most common and malignant intracranial tumors in adults.Recent studies have revealed the significance of functional genomics for glioma pathophysiological studies and treatments.However,access to comprehensive genomic data and analytical platforms is often limited.Here,we developed the Chinese Glioma Genome Atlas(CGGA),a user-friendly data portal for the storage and interactive exploration of cross-omics data,including nearly 2000 primary and recurrent glioma samples from Chinese cohort.Currently,open access is provided to whole-exome sequencing data(286 samples),mRNA sequencing(1018 samples)and microarray data(301 samples),DNA methylation microarray data(159 samples),and microRNA microarray data(198 samples),and to detailed clinical information(age,gender,chemoradiotherapy status,WHO grade,histological type,critical molecular pathological information,and survival data).In addition,we have developed several tools for users to analyze the mutation profiles,mRNA/microRNA expression,and DNA methylation profiles,and to perform survival and gene correlation analyses of specific glioma subtypes.This database removes the barriers for researchers,providing rapid and convenient access to high-quality functional genomic data resources for biological studies and clinical applications.CGGA is available at http://www.cgga.org.cn.
基金supported by the National Natural Science Foundation of China(31830032,81527901,and 31671057)the non-profit Central Research Institute Fund of the Chinese Academy of Medical Sciences(2017PT31038,2018PT31041)+3 种基金the National Key Research and Development Program of China(2016YFA0501000)Key-Area Research and Development Program of Guangdong Province(2018B030334001,2018B030331001)the 111 Project(B13026)the Fountain-Valley Life Sciences Fund of University of Chinese Academy of Sciences Education Foundation and the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-057)。
文摘Major depressive disorder(MDD)is a prevalent psychiatric disease that involves malfunctions of different cell types in the brain.Accumulating studies started to reveal that microglia,the primary resident immune cells,play an important role in the development and progression of depression.Microglia respond to stress-triggered neuroinflammation,and through the release of proinflammatory cytokines and their metabolic products,microglia may modulate the function of neurons and astrocytes to regulate depression.In this review,we focused on the role of microglia in the etiology of depression.We discussed the dynamic states of microglia;the correlative and causal evidence of microglial abnormalities in depression;possible mechanisms of how microglia sense depression-related stress and modulate depression state;and how antidepressive therapies affect microglia.Understanding the role of microglia in depression may shed light on developing new treatment strategies to fight against this devastating mental illness.
基金This work was supported by grants from the National Key Research and Development Program of China(No.2016YFA0100800,2021YFA1101301)the National Natural Science Foundation of China(Grant Nos.82225027,81873994,81820108013,81901902,31727801,82202702,and 82202351)as well as the State Key Program of the National Natural Science Foundation of China(No.81330030).
文摘Spinal cord injury(SCI)remains a severe condition with an extremely high disability rate.The challenges of SCI repair include its complex pathological mechanisms and the difficulties of neural regeneration in the central nervous system.In the past few decades,researchers have attempted to completely elucidate the pathological mechanism of SCI and identify effective strategies to promote axon regeneration and neural circuit remodeling.
基金This work was supported by grants from the Ministry of Science and Technology and the Ministry of Health of the People’s Republic of China(National S&T Major Project of China:2011BAI08B02,2012ZX09303,2013BAI09B14,2013BAI09B03,2015BAI12B02,2015BAI12B04,2017YFC1310900,2017YFC1310901 and 2017YFC1310903)the National Key Technology Research and Development Program of the Ministry of Science and Technology of China(2013BAI09B03)+1 种基金Beijing Municipal Committee of Science and Technology(D15110700200000,D151100002015001,D151100002015002,Z161100000516223 and Z141107002514125)Beijing Institute for Brain Disorders(BIBD-PXM2013_014226_07_000084).
文摘Background In June 2015,the Chinese Stroke Association(CSA)initiated the Chinese Stroke Center Alliance(CSCA)to establish the national hospital-based stroke care quality assessment and improvement platform.This article outlines its objectives,operational structure,patient population,quality improvement(QI)intervention tools,data elements,data collection methodology and current patient and hospital data.Methods The CSCA is a national,hospital-based,multicentre,voluntary,multifaceted intervention and continuous QI initiative.This multifaceted intervention includes stroke centre development,written care protocols,workshops and a monitoring/feedback system of evidencebased performance measures.The data coordinating centre of the CSCA resides at the China National Clinical Research Center for Neurological Diseases,Beijing Tiantan Hospital.results As of July 2017,1576 hospitals in China have contributed detailed clinical information to serve as a benchmark for the stroke care quality of 433264 patients with acute stroke/transient ischaemic attacks(TIA),including 352572(81.38%)acute ischaemic stroke,30362(7.01%)TIA,42080(9.71%)spontaneous intracranial haemorrhage,5505(1.27%)subarachnoid haemorrhage and 2745(0.63%)not specified stroke.Conclusion The CSCA programme is designed to establish a continuous national stroke registry and help healthcare providers develop stroke centres and treat patients in a consistent manner in accordance with accepted national guidelines and,ultimately,improve patient outcomes.It supports the CSA mission to reduce stroke burden in China.
文摘Understanding of the differentiation profile of brain tumor stem cells （BTSCs）, the key ones among tumor cell population, through comparison with neural stem cells （NSCs） would lend insight into the origin of glioma and ultimately yield new approaches to fight this intractable disease. Here, we cultured and purified BTSCs from surgical glioma specimens and NSCs from human fetal brain tissue, and further analyzed their cellular biological behaviors, especially their differentiation property. As expected, NSCs differentiated into mature neural phenotypes. In the same differentiation condition, however, BTSCs exhibited distinguished differences. Morphologically, cells grew flattened and attached for the first week, but gradually aggregated and reformed floating tumor sphere thereafter. During the corresponding period, the expression rate of undifferentiated cell marker CD 133 and nestin in BTSCs kept decreasing, but 1 week later, they regained ascending tendency. Interestingly, the differentiated cell markers GFAP and β-tubulinlII showed an expression change inverse to that of undifferentiated cell markers. Taken together, BTSCs were revealed to possess a capacity to resist differentiation, which actually represents the malignant behaviors of glioma.
基金This work is supported by National Natural Science Foundation of China(81371290),Beijing High-level Personnel Funds(2013-2-019)This study is also funded by the National Science and Technology Support Program of‘The 12th Five-Year Plan’of the Ministry of Science and Technology(2011BAI08B02).
文摘background and purpose A multicentre prospective registry study of individually tailored stenting for a patient with symptomatic intracranial atherosclerotic stenosis(ICAS)combined with poor collaterals in China showed that the short-term safety and efficacy of stenting was acceptable.However,it remained uncertain whether the low event rate could be of a long term.We reported the 1-year outcome of this registry study to evaluate the long-term efficacy of individually tailored stenting for patients with severe symptomatic ICAS combined with poor collaterals.Methods Patients with symptomatic ICAS caused by 70%-99% stenosis located at the intracranial internal carotid,middle cerebral,intracranial vertebral or basilar arteries combined with poor collaterals were enrolled.Balloon-mounted stent or balloon plus self-expanding stent were selected based on the ease of vascular access and lesion morphology determined by the operators.The primary outcome was the rate of 30-day stroke,transient ischaemic attack and death,and 12-month ischaemic stroke within the same vascular territory,haemorrhagic stroke and vascular death after stenting.results From September 2013 to January 2015,300 patients(ages 58.3±9.78 years)were recruited.Among them,159 patients were treated with balloon-mounted stent and 141 with balloon plus self-expanding stent.During the 1-year follow-up,25 patients had a primary end point event.The probability of primary outcome at 1 year was 8.1%(95% CI 5.3% to 11.7%).In 76 patients with digital subtraction angiography follow-up,27.6%(21/76)had re-stenosis≥50% and 18.4%(14/76)had re-stenosis≥70%.No baseline characteristic was associated with the primary outcome.Conclusion The event rate remains low over 1 year of individually tailored stenting for patients with severe symptomatic ICAS combined with poor collaterals.Further randomised trial of comparing individually tailored stenting with best medical therapy is needed.
基金supported by the National Institutes of Health/National Institute of Neurological Disorders and Stroke grant 1R01NS096225-01A1the American Heart Association grants AHA-13SDG1395001413,AHA-17GRNT33660336,AHA-17POST33660174+1 种基金the Louisiana State University Grant in Aid research councilThe Malcolm Feist Cardiovascular Research Fellowship
文摘Cerebral ischemia is one of the leading causes of morbidity and mortality worldwide. Although stroke （a form of cerebral ischemia）-related costs are expected to reach 240.67 billion dollars by 2030, options for treatment against cerebral ischemia/stroke are limited. All therapies except anti-thrombolytics （i.e., tissue plasminogen activator） and hypothermia have failed to reduce neuronal injury, neurological deficits, and mortality rates following cerebral ischemia, which suggests that development of novel therapies again st stroke/cerebral ischemia are urgently needed. Here, we discuss the possible mechanism（s） underlying cerebral ischemia-induced brain injury, as well as current and future novel therapies （i.e., growth factors, nicotinamide adenine dinucleotide, melatonin, resveratrol, protein kinase C isozymes, pifithrin, hypothermia, fatty acids, sympathoplegic drugs, and stem cells） as it relates to cerebral ischemia.
基金supported by the National Natural Science Foundation of China(31871380,32000500,32070730,32170756,32170804,81330008,81671377,81725010,81725010,81872874,81921006,81922027,81971312,81991512,82030041,82103167,82122024,82125009,82125011,82130044,91749126,91949101,91949207,92049302)the National Key Research and Development Program of China(2017YFA0506400,2018YFA0800200,2018YFA0800700,2018YFA0900200,2018YFC2000100,2018YFC2000400,2018YFE-0203700,20192ACB70002,2019YFA0802202,2020YFA0113400,2020YFA0803401,2020YFA0804000,2020YFC2002800,2020YFC-2002900,2021ZD0202401)+11 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16010100,XDA16010603,XDA16020400,XDB29020000,XDB39000000,XDB39000000,XDB39030300)the China Association for Science and Technology(2021QNRC001)the Beijing Municipal Science and Technology Commission(Z200022)the Natural Science Foundation of Shanghai(21JC1406400)the Key Programs of the Jiangxi ProvinceChina(20192ACB70002)the“Shu Guang”Project supported by the Shanghai Municipal Education Commission and Shanghai Education Development Foundation(19SG18)the Shanghai Sailing Program(22YF1434300)the Research Project of Joint Laboratory of University of Science and Technology of China and Anhui Mental Health Center(2019LH03)the Fundamental Research Funds for the Central Universities(WK2070210004)the Young Elite Scientists Sponsorship Program by China Association for Science and Technology(YESS20210002)the Youth Innovation Promotion Association of Chinese Academy of Sciences(2022083)。
文摘Aging is characterized by a progressive deterioration of physiological integrity,leading to impaired functional ability and ultimately increased susceptibility to death.It is a major risk factor for chronic human diseases,including cardiovascular disease,diabetes,neurological degeneration,and cancer.Therefore,the growing emphasis on “healthy aging” raises a series of important questions in life and social sciences.In recent years,there has been unprecedented progress in aging research,particularly the discovery that the rate of aging is at least partly controlled by evolutionarily conserved genetic pathways and biological processes.In an attempt to bring full-fledged understanding to both the aging process and age-associated diseases,we review the descriptive,conceptual,and interventive aspects of the landscape of aging composed of a number of layers at the cellular,tissue,organ,organ system,and organismal levels.
文摘Psychological stress is an important factor for the development of irritable bowel syndrome(IBS). More and more clinical and experimental evidence showed that IBS is a combination of irritable bowel and irritable brain. In the present review we discuss the potential role of psychological stress in the pathogenesis of IBS and provide comprehensive approaches in clinical treatment. Evidence from clinical and experimental studies showed that psychological stresses have marked impact on intestinal sensitivity, motility, secretion and permeability, and the underlying mechanism has a close correlation with mucosal immune activation, alterations in central nervous system, peripheral neurons and gastrointestinal microbiota. Stress-induced alterations in neuro-endocrine-immune pathways acts on the gut-brain axis and microbiota-gut-brain axis, and cause symptom flare-ups or exaggeration in IBS. IBS is a stresssensitive disorder, therefore, the treatment of IBS should focus on managing stress and stress-induced responses. Now, non-pharmacological approaches and pharmacological strategies that target on stress-related alterations, such as antidepressants, antipsychotics, miscellaneous agents, 5-HT synthesis inhibitors, selective 5-HT reuptake inhibitors, and specific 5-HT receptor antagonists or agonists have shown a critical role in IBS management. A integrative approach for IBS management is a necessary.
基金We would like to apologize to those researchers whose related work we were not able to cite in this review.This work was supported by a special program from the Ministry of Science and Technology of China(2021YFA1101000)the Chinese National Natural Science Funds(31925013 and U20A20393 to L.Z.,31871405,32125016 and 82041009 to F.Z.)+5 种基金Zhejiang Provincial Natural Science Foundation of China under Grant(LBY21H060001 to L.Z.)the Medical and the Medical and Health Research Project of Zhejiang Province(2020RC115 to L.Z.)Jiangsu National Science Foundation(BK20180043 and 19KJA550003 to F.Z.)the Zhejiang Natural Science Fund(LD19C070001to L.Z.)the Key Project of University Natural Science Foundation of Jiangsu Province(19KJA550003)A project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions,and the Medical and Health Research Project of Zhejiang Province(2020RC155 to L.Z.).
文摘Since the outbreak of the coronavirus disease 2019(COVID-19)pandemic,there have been a few variants of the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),one of which is the Omicron variant(B.1.1.529).The Omicron variant is the most mutated SARS-CoV-2 variant,and its high transmissibility and immune evasion ability have raised global concerns.Owing to its enhanced transmissibility,Omicron has rapidly replaced Delta as the dominant variant in several regions.However,recent studies have shown that the Omicron variant exhibits reduced pathogenicity due to altered cell tropism.In addition.
基金Grant-in-Aids for Scientific Research(B:No.16390100 and 19390096)Asia-Africa Scientific Platform Program(AASPP)+1 种基金the Japan Society for the Promotion of Science(JSPS)a Grant for Child Health and Development(17-2 and 20-2)the Ministry of Health,Labour and Welfare in Japan
文摘Citrin deficiency,autosomal recessive disorder,caused by mutation of SLC25A13 gene on chromosome 7q21.3 has two major phenotypes:neonatal intrahepatic cholestatic hepatitis(NICCD)and adult-onset type Ⅱ citrullinemia(CTLN2).So far,we have identified 52 SLC25A13 mutations and diagnosed the patients not only in Japan(166 CTLN2 and 238 NICCD) but also in other countries.We have detected 76 Chinese,13 Korean and 15 Vietnamese patients with the same mutations as Japanese,and 13 patients(from Israel,UK,USA or Czech)with mutations different from those found in Japanese,indicating a wide distribution of citrin deficiency.DNA diagnoses of 13 known SLC25A13 mutations revealed that the carrier frequency was high in East Asian populations:Chinese(73/4 600=1/63),Japanese(21/1 372=1/65) and Korean(25/2 690=1/108),suggesting that near by 100 000 East Asians are homozygotes.It is important to find out patients with citrin deficiency,to treat them,and to prevent onset of severe CTLN2.
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.
