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B淋巴细胞刺激因子和增殖诱导配体在神经免疫性疾病中的作用

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中华神经科杂志 2024年第6期57卷 661-669页

作者：丁婕管阳太上海交通大学医学院附属仁济医院神经内科上海200127

B淋巴细胞刺激因子(BLyS)和增殖诱导配体(APRIL)是肿瘤坏死因子超家族成员,两者有较强同源性。作为淋巴细胞共刺激因子,能调节多种生物学功能,可调节细胞分化、增殖、存活和效应功能,特别是在调节B细胞和T细胞等免疫功能中发挥重要作用... 详细信息

B淋巴细胞刺激因子(BLyS)和增殖诱导配体(APRIL)是肿瘤坏死因子超家族成员,两者有较强同源性。作为淋巴细胞共刺激因子,能调节多种生物学功能,可调节细胞分化、增殖、存活和效应功能,特别是在调节B细胞和T细胞等免疫功能中发挥重要作用。BLyS/APRIL在视神经脊髓炎谱系疾病、多发性硬化、重症肌无力等神经免疫性疾病的发生发展中起重要作用。本文旨在提升对BLyS/APRIL及其在神经免疫性疾病中作用的认识。

关键词： B细胞活化因子增殖诱导配体神经免疫性疾病发病机制视神经脊髓炎谱系疾病

Novel drug-delivery approaches to the blood-brain barrier

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Neuroscience Bulletin 2015年第2期31卷 257-264页

作者： Xiaoqing Wang Xiaowen Yu William Vaughan Mingyuan Liu yangtai guan Department of Neurology Changhai Hospital Second Military Medical University Stem Cells and Medical Research Center Second Military Medical University Department of Gerontology Changhai Hospital Second Military Medical University Department of Genetics Yale University

The blood-brain barrier （BBB） maintains homeostasis by blocking toxic molecules from the circulation, but drugs are blocked at the same time. When the dose is increased to enhance the drug concentration in the central nervous system, there are side-effects on peripheral organs. In recent years, genetic therapeutic agents and small molecules have been used in various strategies to penetrate the BBB while minimizing the damage to systemic organs. In this review, we describe several representative methods to circumvent or cross the BBB, including chemical and physical strategies.

关键词： drug delivery blood-brain barrier nanoparticles focused ultrasound

Case report of rabies-induced persistent mental symptoms

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上海精神医学 2015年第1期27卷 52-54页

作者： Xiaoqing WANG Xiaowen YU yangtai guan DepartmentofNeurology ChanghaiHospitalShanghaiSecondMilitaryMedicalUniversity DepartmentofNeurology RenjiHospitalShanghaiJiaotongUniversitySchoolofMedicine

Rabies is a viral infection with a high case fatality rate. Typical symptoms of rabies include hydrophobia, pharynx muscle spasms, and progressive paralysis. Rabies-induced persistent mental disturbances are rare. Here we report a 22-year-old male who was infected with rabies after being attacked by a dog. He did not receive rabies vaccine immediately after the incident and was only provided with non-standard treatment at a local clinic. A week later he became disorientated, paranoid, and aggressive. One month after the attack, rabies antibody was found in his cerebrospinal fluid and a Magnetic Resonance Imaging (MRI) examination of his head revealed abnormal signals in the putamina, caudate nucleus, and insula. His mental symptoms persisted for six years and his daily functioning was severely impaired, but his vital signs were stable without signs of brain stem damage. Six years after the incident, a repeat MRI showed brain atrophy.

关键词：典型症状精神障碍狂犬病持续性病例报告病毒感染磁共振成像狂犬疫苗

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Neural Regeneration Research 2010年第16期5卷 1231-1237页

作者： Jianming Jiang Long Yu yangtai guan Zhiliang Yu Xinghua Huang Xiaosong Chen LishaTang Xianning Zhang Department of Neurology Changhai Hospital Second Military Medical University Shanghai 200433 China State Key Laboratory of Genetic Engineering Institute of Genetics School of Life Science Fudan University Shanghai 200433 China Zhejiang University-Adinovo Center for Genetic and Genomic Medicine Zhejiang University School of Medicine Hangzhou 310058 Zhejiang Province China

Epilepsy is a complex, Mendelian disease, and most cases are sporadic. Genomic comparisons of tissue from identified monogenic epilepsies with multigenic and acquired syndromes could ultimately reveal crucial molecular neuropathology for an epileptic phenotype. In the present study, a novel gene, human seizure-related （hSEZ）-6, was isolated from a human brain cDNA library. hSEZ-6 comprises 17 exons and spans a region of at least 55.6 kb, which was localized to 17q 12 by radiation hybridization, hSEZ-6 exhibits two isoform types, hSEZ-6A and hSEZ-6B, which encode 996 and 995 amino acids, respectively. The two putative hSEZ-6 proteins contain similar motifs and share 82% and 84% identity with mouse SEZ-6A protein, whose expression level increased in mouse cerebral cortex-derived cells treated with a convulsant drug, pentylentetrazole. Northern blot analysis demonstrated that hSEZ-6 is expressed highly in the cerebellum and in nucleus of the extrapyramidal system, such as the caudate nucleus and putamen. Reverse transcription polymerase chain reaction revealed that hSEZ-6 is expressed in neurons rather than gliocytes, which suggests that hSEZ-6 is a seizure-related gone.

关键词： seizures epilepsy human seizure-related-6 gene cloning brain-specific expression cerebellum

Correlation between human seizure-related gene 6 variants and idiopathic generalized epilepsy in a Southern Chinese Han population

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Neural Regeneration Research 2012年第2期7卷 96-100页

作者： Jianming Jiang Xiao ling Chen Wenting Liu Yan Zhao yangtai guan Yan Han FengWang Jiajun Lu Zhiliang Yu Zhenfang Du Xianning Zhang Department of Neurology Changhai Hospital Second Military Medical University of Chinese PLA Shanghai 200433 China Department of Biochemistry ＆ Genetics the National Education Base for Basic Medical Sciences Institute of Cell Biology ZhejiangUniversity School of Medicine Hangzhou 310058 Zhejiang Province China

This study sought to analyze the genotype and gene mutations of human seizure-related gene 6 in 98 patients with idiopathic generalized epilepsy （non-febrile seizures）, who were selected from three generations of the Chinese Han population living in Shanghai, Zhejiang Province, Wuxi of Jiangsu Province, and Jiangxi Province of Southern China. Twenty-six patients＇ parents were available as a first-degree relatives group and 100 biologically unrelated healthy controls were collected as the control group. Based on the age of onset and seizure type, the patients were divided into six subgroups. Polymerase chain reaction and DNA direct sequencing analysis showed that the most frequent mutations c. 1249dupC （p.Gly418Argfx31 ） and c.1636A 〉 G （p.Thr546Ala） were detected in some idiopathic generalized epilepsy patients and tl^eir asymptomatic first-degree relatives （30.6% vs. 19.2% and 11.2% vs. 26.9%）. A novel mutation c.1807G 〉A （p.Val603Met） was found in a patient with late-onset idiopathic generalized epilepsy. There was no significant difference in the incidence of these three mutations among the different subgroups of idiopathic generalized epilepsy and controls. Thus, further analysis of a larger population is needed to confirm the assumption that human seizure-related gene 6 is a susceptibility gene for idiopathic generalized epilepsy with various sub-syndromes.

关键词： human seizure-related gene 6 non-febrile seizure generalized epilepsy mutation polymorphism, genetic neural regeneration

探索多维度节点化过程考核模式在神经内科住院医师规范化培训中的应用

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中国毕业后医学教育 2024年第6期8卷 436-439页

作者：潘元美冯智英施国文姚小英戴若莲管阳太上海交通大学医学院附属仁济医院神经内科上海200127

目的探讨多维度节点过程考核模式在神经内科住院医师规范化培训中(简称住培)的应用效果。方法选取2019级—2022级的神经内科住院医师11人,其中2021级、2022级7人为观察组,采取多维度节点化考核,共进行10次;2019级、2020级4人为对照组... 详细信息

目的探讨多维度节点过程考核模式在神经内科住院医师规范化培训中(简称住培)的应用效果。方法选取2019级—2022级的神经内科住院医师11人,其中2021级、2022级7人为观察组,采取多维度节点化考核,共进行10次;2019级、2020级4人为对照组,采取传统考核方式。结果观察组培训效果显著提高,理论知识、病史采集和病例分析考试成绩均显著高于对照组,差异有统计学意义(均P<0.05)。同时,国家年度水平测试中,观察组成绩较对照组提升了12.7%。结论多维度节点化过程考核有助于神经病学专业知识的掌握和临床思维能力的提升,值得进一步探索和推广。

关键词：住院医师规范化培训神经内科过程考核多维度节点化考核

Study of PTEN Inhibition of the Downstream Molecular Mechanism to Promote CNS Axonal Regrowth after Ischemic Stroke

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Effect of PTEN Inhibitor bpv on the Axonal Regrowth and Functional Recovery of Cerebral Ischemia Reperfusion Injury in Mice

山东省2013年神经内科学学术会议暨中国神经免疫大会2...

作者： Lunlin Mao Jian Cheng yangtai guan Department of Neurology Changhai HospitalSecond Military Medical University Institute of Neuroscience Soochow University

＜正＞Objectives:To study whether the PTEN inhibitors bpv ischemia increase AKT and mTOR activity post-ischemic,as well as promotes neurite outgrowth on primary cortical neurons in vitro OGD model,To investigate the PTEN inhibition’s downstream molecular mechanisms in the promotion of CNS axonal regrowth after ischemic stroke. Methods:A potent PTEN inhibitor bpv at the doses of 0.2mg/kg/daily via a intra-peritoneal routes, starting at 24 hours after reperfusion;At the time point 96h after reperfusion,Cortical and striatal tissue were harvested from ischemic boundary zones （IBZ）and contralateral of the bpv treatment group and Saline group,use Western-blot to detect protein expression of AKT,p-AKT,S6,p-S6.Isolated from mouse embryos,cultured primary cortical nerve cells, after 7 days,1h OGD to the neurons,then divided into five groups:200nM bpv group,100nM bpv treatment group,50nM bpv treatment group,20nM bpv group and 2μl Saline group.They are placed in a C02 incubator,After 24 hours re-oxygenation, immunostaining was performed using antibodies against TUJ1 to assess dendrite outgrowth under the fluorescence microscope,determine the dose of bpv promote neurite outgrowth of neurons after OGD. After that,processing lh OGD to neurons,then divided into four groups:bvp +mTOR inhibitor （rapamycin-100nM） group,bpv+AKT inhibitors （LY294002,10μM）,bpv+DMSO and Saline group. They are placed in a CO2 incubator,After 24 hours re-oxygenation,immunostaining was performed using antibodies against TUJ1 to assess dendrite outgrowth under the fluorescence microscope, determine PTEN inhibition promote ischemic downstream molecular mechanism of CNS axonal regrowth after stroke. Results:The bpv group significantly increased phosphorylation of AKT and S6 in the Cortical and striatal IBZ at 96h after reperfusion compared to saline injection.After 24h re-oxygenation,the neurite length is 200.51±35.98um in lOOnM bpv group,much higher than the others（P＜0.001）.After 24h re-oxygenation,the neurite length is 210.80±49.34um in bpv+DMSO group,much

关键词： PTEN PCN OGD AKT mTOR

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Effect of PTEN Inhibitor bpv on the Axonal Regrowth and Func...

An ASA Based Feedforward Control of Skeleton Post-Stroke Rehabilitation Robot System

山东省2013年神经内科学学术会议暨中国神经免疫大会2...

作者： Lunlin Mao Jian Cheng yangtai guan Department of Neurology Changhai HospitalSecond Military Medical University Institute of Neuroscience Soochow University

＜正＞Objectives:Study on the effect of PTEN inhibitor bpv on the axonal regrowth and functional recovery of cerebral ischemia reperfusion injury in mice,and explore whether PTEN is the endogenous inhibition mechanism of the axonal regrowth after stroke. Methods:Firstly,according to the modified Zea-Longa suture method,build MCAO-reperfusion injury model.Cerebral ischemia and reperfusion,at the time point of 1d,3d,7d,14d,Cortical and striatal tissue were harvested from ischemic boundary zones and contralateral separately,use Western-blot technique to detect the p-PTEN and PTEN protein’s expression at each time point of each group.Secondly, the animals were randomly divided into 3 groups: Sham group;MCAO + saline group;MCAO+ bpv group,a potent PTEN inhibitor bpv at the doses of 0.2mg/kg/daily via a intra-peritoneal route for 14 days,starting at 24 hours after reperfusion;. MCAO+Saline is injected with the same dose of saline.After 96h,we use TTC staining and compare each group’s cerebral infarction volume,observe the mortality of animals after 14 days ischemia and the cortical width index at the time point:1d,3d,5d,7d, 9d,14d,we use NSS and forelimb placement test to assess the changes of neurological function in each group.We use Bielschowsky Silve staining method to show the distribution of axons within the white matter tracts at the edge of the cerebral ischemia,we use IHC to detect MBP and protein-43’s（GAP-43） expression which is associated with growth on the ischemic border zone. Results:During the animal ischemia reperfusion 1-14 days,total PTEN protein showed persistent high levels of expression in the ischemic cortex and striatum,no significant decrease compared with the Sham;Also no significant changes on cerebral ischemia phosphorylation of PTEN protein’s（non-activated） level compared with the Sham,the levels of phosphorylated and total PTEN protein expression,also its ratio in the contralateral cortex and striatum,compared with the Sham,have no significant changes（P＞0.05）.After 96h ischemia and reperfusion

关键词： PTEN cerebral ischemia/reperfusion injury axonal regrowth Mice

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An ASA Based Feedforward Control of Skeleton Post-Stroke Reh...