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Multiple factors to assist human-derived induced pluripotent stem cells to efficiently differentiate into midbrain dopaminergic neurons

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Neural Regeneration Research 2024年第4期19卷 908-914页

作者： Yalan Chen Junxin Kuang Yimei Niu Hongyao Zhu Xiaoxia Chen Kwok-Fai So anding xu Lingling Shi Guangdong-Hong Kong-Macao Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan University Department of Neurology and Stroke Center The First Affiliated HospitalJinan University Department of Psychiatry The First Affiliated HospitalJinan University Co-innovation Center of Neuroregeneration Nantong University

Midbrain dopaminergic neurons play an important role in the etiology of neurodevelopmental and neurodegenerative *** also represent a potential source of transplanted cells for therapeutic *** vitro differentiation of functional midbrain dopaminergic neurons provides an accessible platform to study midbrain neuronal dysfunction and can be used to examine obstacles to dopaminergic neuronal *** evidence and impressive advances in human induced pluripotent stem cells,with tuned neural induction and differentiation protocols,makes the production of induced pluripotent stem cell-derived dopaminergic neurons *** SB431542 and dorsomorphin dual inhibitor in an induced pluripotent stem cell-derived neural induction protocol,we obtained multiple subtypes of neurons,including 20%tyrosine hydroxylase-positive dopaminergic *** obtain more dopaminergic neurons,we next added sonic hedgehog(SHH)and fibroblast growth factor 8(FGF8)on day 8 of *** increased the proportion of dopaminergic neurons,up to 75%tyrosine hydroxylase-positive neurons,with 15%tyrosine hydroxylase and forkhead box protein A2(FOXA2)co-expressing *** further optimized the induction protocol by applying the small molecule inhibitor,CHIR99021(CHIR).This helped facilitate the generation of midbrain dopaminergic neurons,and we obtained 31-74%midbrain dopaminergic neurons based on tyrosine hydroxylase and FOXA2 ***,we have established three induction protocols for dopaminergic *** on tyrosine hydroxylase and FOXA2 immunostaining analysis,the CHIR,SHH,and FGF8 combined protocol produces a much higher proportion of midbrain dopaminergic neurons,which could be an ideal resource for tackling midbrain-related diseases.

关键词： dopaminergic neurons FGF signal induced pluripotent stem cells midbrain neural differentiation SHH signal SMAD signal WNT signal

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Increased retinal venule diameter as a prognostic indicator for recurrent cerebrovascular events:a prospective observational study

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Neural Regeneration Research 2024年第5期19卷 1156-1160页

作者： Ying Zhao Dawei Dong Ding Yan Bing Yang Weirong Gui Man Ke anding xu Zefeng Tan Department of Neurology and Stroke Center the First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina Clinical Neuroscience Institute the First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina Department of Neurology the First People’s Hospital of FoshanFoshanGuangdong ProvinceChina

Microvasculature of the retina is considered an alternative marker of cerebral vascular risk in healthy ***,the ability of retinal vasculature changes,specifically focusing on retinal vessel diameter,to predict the recurrence of cerebrovascular events in patients with ischemic stroke has not been determined *** previous studies have shown a link between retinal vessel diameter and recurrent cerebrovascular events,they have not incorporated this information into a predictive ***,this study aimed to investigate the relationship between retinal vessel diameter and subsequent cerebrovascular events in patients with acute ischemic ***,we sought to establish a predictive model by combining retinal veessel diameter with traditional risk *** performed a prospective observational study of 141 patients with acute ischemic stroke who were admitted to the First Affiliated Hospital of Jinan *** of these patients underwent digital retinal imaging within 72 hours of admission and were followed up for 3 *** found that,after adjusting for related risk factors,patients with acute ischemic stroke with mean arteriolar diameter within 0.5-1.0 disc diameters of the disc margin(MAD_(0.5-1.0DD))of≥74.14μm and mean venular diameter within 0.5-1.0 disc diameters of the disc margin(MVD_(0.5-1.0DD))of≥83.91μm tended to experience recurrent cerebrovascular *** established three multivariate Cox proportional hazard regression models:model 1 included traditional risk factors,model 2 added MAD_(0.5-1.0DD)to model 1,and model 3 added MVD0.5-1.0DD to model *** 3 had the greatest potential to predict subsequent cerebrovascular events,followed by model 2,and finally model *** findings indicate that combining retinal venular or arteriolar diameter with traditional risk factors could improve the prediction of recurrent cerebrovascular events in patients with acute ischemic stroke,and that retinal imaging c

关键词： acute ischemic stroke arteriolar cerebrovascular events diameter digital retinal imaging microvasculature prediction recurrent retina venular

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集成平台在医院信息化建设中的应用

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移动信息 2024年第4期46卷 79-81页

作者：许岸铤中国人民大学北京100000

随着医疗技术的日新月异和信息化社会的快速发展,信息化已经成为医疗机构提升服务质量,提高工作效率,降低运营成本的重要手段。而在医院信息化建设中,集成平台的应用至关重要。文中探讨了集成平台在医院信息化中的应用。医院信息化集成... 详细信息

随着医疗技术的日新月异和信息化社会的快速发展,信息化已经成为医疗机构提升服务质量,提高工作效率,降低运营成本的重要手段。而在医院信息化建设中,集成平台的应用至关重要。文中探讨了集成平台在医院信息化中的应用。医院信息化集成平台是一种将医院内各部门、各系统、各数据源进行整合与互操作的系统平台,它通过标准化接口和统一的数据交换格式,实现医院内部信息的共享与传递、医院与外部系统的信息交互。通过集成平台,医院可以实现数据的互通互联和信息的共享共用,提高医疗服务的效率和质量,提升医院的管理水平和社会形象。

关键词：医疗信息集成平台医院建设

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Value of cerebral perfusion and vascular reserve for the treatment of symptomatic intracranial arterial stenosis

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Neural Regeneration Research 2008年第1期3卷 79-82页

作者： Li＇an Huang xuewen Song anding xu Department of Neurology First Affiliated Hospital of Jinan University Guangdong 510632 Guangzhou Province China

BACKGROUND： It is crucial to understand cerebral perfusion and vascular reserve in stegnotic arterial blood-supply regions to treat ischemic cerebrovascular diseases. However, effects on symptomatic intracranial arterial stenosis （SICAS） need to be further studied in additional applications. OBJECTIVE： To evaluate and summarize the effects of cerebral perfusion and vascular reserve on the treatment of SICAS. RETRIEVAL STRATEGY： A computer-based online search of English language publications from January 2000 to July 2007 was conducted in PubMed to identify publications that addressed cerebral perfusion and vascular reserve of SICAS. Search key words were ＂intracranial stenosis, perfusion, brain reserve＂. Relevant data were also searched with the China Journal Net, using the same key words in Chinese from January 2000 to January 2007. In total, 101 articles were retrieved. Inclusion criteria：（1） Articles describing the current status for the diagnosis and treatment of SICAS; （2） Articles concerning research developments of cerebral perfusion and vascular reserve of SICAS. Exclusion criteria： duplicated articles. LITERATURE EVALUATION： This study included 21 articles of experimental studies and conference reports. DATA SYNTHESIS： When performing interventional surgery in SICAS patients, it is important to understand cerebral perfusion and vascular reserve in addition to knowing the clinical symptoms and degrees of arterial stenosis. In recent years, there are a growing number of reports on measurements of vascular reserve through the use of magnetic resonance perfusion imaging （MR-PWI）. Investigations demonstrate cerebral perfusion and vascular reserve decrease in many SICAS patients. Many studies show that both improve after surgical intervention. CONCLUSION： Cerebral perfusion could provide direct evidence of whether ischemia has occurred in the brain. Because of lateral circulation and cerebral vascular reserve, intracranial vascular stenosis and/or decreased intr

关键词： intracranial stenosis perfusion brain reserve

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Cerebral perfusion in corresponding blood supply areas of transient ischemic attack patients with intracranial stenosis Seven cases of diamox-perfusion verified by magnetic resonance-perfusion-weighted imaging

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Neural Regeneration Research 2010年第1期5卷 58-63页

作者： Li'an Huang xuewen Song anding xu xueying Ling Zhichao Lin Department of Neurology First Affiliated Hospital of Jinan University Guangzhou 510632 Guangdong Province China Department of Radiology First Affiliated Hospital of Jinan University Guangzhou 510632 Guangdong Province China

BACKGROUND： Due to collateral circulation and cerebrovascular reserve, arterial stenosis and reduced cerebral blood flow may not necessarily indicate impaired cerebral peffusion. Therefore, according to degree of stenosis and clinical symptoms, interventional surgery to relieve arterial stenosis in transient ischemic attack （TIA） patients with major intracranial stenosis is imprudent. Rather, cerebral perfusion and reserve capacity are direct indicators for the assessment of degree and presence of cerebral ischemia. OBJECTIVE： To evaluate cerebral perfusion and reserve in TIA patients with major intracranial stenosis or occlusion using magnetic resonance-perfusion-weighted imaging （MR-PWl） data prior to and following diamox administration. DESIGN, TIME AND SETTING： A self-comparative, neuroimaging observation was performed at the Neurological Department and Radiological Center of the First Affiliated Hospital of Jinan University between December 2007 and April 2009. PARTICIPANTS： Seven acute TIA patients, who were admitted to the Neurological Department of the First Affiliated Hospital of Jinan University between December 2007 and April 2009, were enrolled in the present study. Magnetic resonance imaging confirmed that no acute cerebral infarction happened, nor did bleeding exist. Magnetic resonance angiography, transcranial Doppler ultrasound, and/or digital subtraction angiography confirmed the presence of major intracranial arterial stenosis. Clinical symptoms corresponded to blood supplying regions of the arterial stenosis. METHODS： Baseline MR-PWI was performed on seven patients with intracranial stenosis or occlusion. Two grams of acetazolamide （diamox） were orally administered after 2 days. A second PWl was performed after 2 hours to compare cerebral perfusion parameters prior to and following diamox administration. MAIN OUTCOME MEASURES： PWI results of cerebral perfusion prior to and following diamox administration. RESULTS： The baseline PWl from five patien

关键词： transient ischemic attack stenosis magnetic resonance-perfusion-weighted imaging diamox cerebral perfusion cerebral reserve capacity

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Changing the strategy and culture of stroke awareness education in China: implementing Stroke 1-2-0

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Stroke & Vascular Neurology 2020年第4期5卷 374-380页

作者： Jing Zhao xutong Li Xiaochuan Liu Yuming xu Jihong xu anding xu Yongjun Wang Renyu Liu Neurology Minhang HospitalFudan UniversityShanghaiChina Department of Neurology Fudan UniversityShanghaiChina Wannan Medical College WuhuChina Zhengzhou University First Affiliated Hospital ZhengzhouChina Anesthesiology and Critical Care University of Pennsylvania Perelman School of MedicinePhiladelphiaPennsylvaniaUSA Department of Neurology and Stroke Center Jinan University First Affiliated HospitalGuangzhouChina China National Clinical Research Center for Neurological Disease BeijingChina Neurology Tiantan Hospital Affiliated to Capital Medical UniversityBeijingChina

This project implemented the Stroke1-2-0 stroke awareness programme across China and investigated its impact over a 2-year *** initiated the Stroke1-2-0 educational campaign and Stroke1-2-0 special task forces(STF)across the *** media coverage,community-based educational sessions with videos and other related materials and induction of Stroke1-2-0 STF were the major means of *** delivered a survey at the end of 2016 and 2018 to evaluate the impact of our effort.A total of 3066 participants responded to the first survey in 2016,and 15207 participants responded in 2018 across *** acceptance rate for Stroke1-2-0 versus FAST(an English-language stroke awareness tool)was 50.2%versus 19.1%in 2016,and changed significantly to 82.2%versus 8.0%in 2018(p<0.001).Stroke1-2-0 was well accepted by all ages and by people with different academic *** 6.5%of survey respondents were aware that there was a therapeutic window for thrombolytic therapy in 2016,but this awareness increased significantly to 32.8%in *** 12.6%of people in 2016 indicated that they would send patients with stroke to the nearest hospital capable of performing thrombolytic therapy,but there was a nearly threefold increase(52.5%)in this number by *** than 1000 major hospitals joined the Stroke1-2-0 STF,and more than 20000‘stroke warriors’have joined our stroke awareness improvement effort so ***1-2-0 stroke awareness programme is well-implemented and accepted,and is generating profound improvement in stroke awareness in China.

关键词： education culture awareness

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Associations of HDL-C/LDL-C with myocardial infarction,all-cause mortality,haemorrhagic stroke and ischaemic stroke:a longitudinal study based on 384093 participants from the UK Biobank

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Stroke & Vascular Neurology 2023年第2期8卷 119-126页

作者： Shiqi Yuan Xiaxuan Huang Wen Ma Rui Yang Fengshuo xu Didi Han Tao Huang MIn Peng anding xu Jun Lyu Department of Neurology Jinan University First Affiliated HospitalGuangzhouGuangdongChina School of Public Health Xi'an Jiaotong UniversityXi'anShaanxiChina Department of Clinical Research Jinan University First Affiliated HospitalGuangzhouGuangdongChina Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization GuangzhouGuangdongChina

Objective To explore the correlations of high-density lipoprotein cholesterol(HDL-C)/low-density lipoprotein cholesterol(LDL-C)with myocardial infarction(MI),all-cause mortality,haemorrhagic stroke and ischaemic stroke,as well as the joint association of genetic susceptibility and HDL-C/LDL-C with the MI *** and results This study selected 384093 participants from the UK Biobank(UKB)***,restricted cubic splines indicated non-linear associations of HDL-C/LDL-C with MI,ischaemic stroke and all-cause ***,a Cox proportional-hazards model indicated that compared with HDL-C/LDL-C=0.4-0.6,HDL-C/LDL-C0.6 were correlated with all-cause mortality(HR=0.97 for HDL-C/LDL-C0.6,95%CI=1.16 to 1.26,p0.6 was associated with higher risk haemorrhagic stroke risk after full multivariable adjustment(HR=1.25,95%CI=1.03 to 1.52,p<0.05).Third,after calculating the coronary heart disease Genetic Risk Score(CHD-GRS)of each participant,the Cox proportional-hazards model indicated that compared with low CHD-GRS and HDL-C/LDL-C=0.4-0.6,participants with a combination of high CHD-GRS and HDL-C/LDL-C<0.4 were associated with the highest MI risk(HR=2.45,95%CI=2.15 to 2.8,p<0.001).Participants with HDL-C/LDL-C<0.4 were correlated with a higher MI risk regardless of whether they had a high,intermediate or low *** In UKB participants,HDL-C/LDL-C ratio of 0.4-0.6 was correlated with lower MI risk,all-cause mortality,haemorrhagic stroke and ischaemic *** with HDL-C/LDL-C<0.4 were correlated with a higher MI risk regardless of whether they had a high,intermediate or low *** clinical significance and impact of HDL-C/LDL-C need to be further

关键词： infarction haemorrhagic restricted

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The Chinese Stroke Association scientific statement:intravenous thrombolysis in acute ischaemic stroke

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Stroke & Vascular Neurology 2017年第3期2卷 147-159页

作者： Qiang Dong Yi Dong Liping Liu anding xu Yusheng Zhang Huaguang Zheng Yongjun Wang 无 Department of Neurology Huashan Hospital affiliated to Fudan UniversityShanghai ShiChina Department of Neurology Beijing Tiantan Hospital affiliated to Capital Medical UniversityBeijingChina Department of Neurology and Stroke Center First Affiliated HospitalJinan UniversityGuangzhou ShiChina On behalf of the CSA Scientific Statement on Intravenous Thrombolysis in Acute Ischemic Stroke Writing Group

The most effective medical treatment for acute ischaemic stroke(AIS)is to offer intravenous thrombolysis during the ultra-early period of time after the *** based on the Consensus of Chinese Experts on Intravenous Thrombolysis for AIS in 2012 and 2014 Chinese Guidelines on the Diagnosis and Treatment of AIS,the rate of thrombolysis for AIS in China remained around 2.4%,and the rate of intravenous tissue plasminogen activator usage was only about 1.6%in real *** indication of thrombolysis for AIS has been expanded,and contraindications have been reduced with recently published *** order to facilitate the standardisation of treating AIS,improve the rate of thrombolysis and benefit patients who had a stroke,Chinese Stroke Association has organised and developed this scientific statement.

关键词： thrombolysis intravenous acute

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Clopidogrel loading dose versus maintenance dose to treat patients with acute ischaemic stroke in China(CLASS-China):results from a prospective double-blind randomised clinical trial

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Stroke & Vascular Neurology 2017年第3期2卷 118-123页

作者： Ying Zhao Wanyong Yang Zefeng Tan Wenmin Wang Weimin Xiao Jinsheng Zeng anding xu Department of Neurology and Stroke Center The First Affiliated HospitalJinan UniversityGuangzhouChina Department of Neurology The First Affiliated HospitalKunming Medical CollegeKunmingYunnanChina Department of Neurology Dongguan People HospitalDongguanGuangdongChina Department of Neurology and Stroke Center First Affiliated HospitalSun Yat-Sen UniversityGuangzhouGuangdongChina

Aim The role of clopidogrel in treating patients with acute ischaemic stroke is *** have conducted the clinical trial in order to evaluate the efficacy and safety of clopidogrel with a loading dose in treating patients with non-cardiogenic acute ischaemic *** Clopidogrel loading dose versus maintenance dose to treat patients with acute ischaemic stroke in China(CLASS-China)was a prospective,randomised,double-blind and placebo-controlled clinical trial in *** with acute ischaemic stroke of non-cardiogenic origin within 48 hours of onset were enrolled and those received thrombolysis were *** patients were divided into two treatment groups:loading dose and routine *** primary outcome was the incidence of stroke recurrence or progression within 7 *** safety outcome was measured by life-threatening *** intent-to-treat analysis was used for the statistical *** From March 2008 to March 2010,a total of 303 patients from 16 centres were recruited into this study;six were excluded because of lack of basic *** the enrolment was slow and the study drug expired in March 2010,this clinical trial was stopped earlier than *** significant baseline and demographic differences were seen between the two *** was no difference in primary outcome between the loading dosage group 16.1%(24/149)and control group 14.9%(22/148),respectively(p=0.782).The mortality and disability rate within 90 days in loading dose group(19.6%)was slightly lower than that in controlled group(23.4%),p=*** dose group had two(1.3%)cases of fatal haemorrhage and control group had four(2.7%)within 90 days,p=*** significant difference was detected in other adverse events between the *** In our study stopped early due to slow enrolment,loading dose of clopidogrel does not reduce the risk of recurrent *** trials with sufficient number of patients enrolled are needed to re-e

关键词： patients dosage routine

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FUS-mediated HypEVs: Neuroprotective effects against ischemic stroke

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Bioactive Materials 2023年第11期29卷 196-213页

作者： Yousheng Wu Xiaoxiong Huang Zefeng Tan Jiankun Zang Min Peng Niu He Tao Zhang Hongcheng Mai anding xu Dan Lu Department of Neurology and Stroke Center The First Affiliated Hospital of Jinan UniversityGuangzhouChina Clinical Neuroscience Institute The First Affiliated Hospital of Jinan UniversityGuangzhouChina Key Lab of Guangzhou Basic and Translational Research of Pan-vascular Diseases The First Affiliated Hospital of Jinan UniversityGuangzhouChina Department of Neurology and Stroke Center The Central Hospital of ShaoyangHunanChina Department of Neurology The First People’s Hospital of FoshanGuangdongChina Department of Cardiology The First Affiliated Hospital of Jinan UniversityGuangzhouChina Munich Medical Research School(MMRS) Ludwig-Maximilians University MunichMunichGermany Insititute for Tissue Engineering and Regenerative Medicine(iTERM) Helmholtz Zentrum MünchenNeuherbergGermany

Few studies have investigated the properties and protein composition of small extracellular vesicles (sEVs) derived from neurons under hypoxic conditions. Presently, the extent of the involvement of these plentiful sEVs in the onset and progression of ischemic stroke remains an unresolved question. Our study systematically identified the characteristics of sEVs derived from neurons under hypoxic conditions (HypEVs) by physical characterization, sEV absorption, proteomics and transcriptomics analysis. The effects of HypEVs on neurites, cell survival, and neuron structure were assessed in vitro and in vivo by neural complexity tests, magnetic resonance imaging (MRI), Golgi staining, and Western blotting of synaptic plasticity-related proteins and apoptotic proteins. Knockdown of Fused in Sarcoma (FUS) small interfering RNA (siRNA) was used to validate FUS-mediated HypEV neuroprotection and mitochondrial mRNA release. Hypoxia promoted the secretion of sEVs, and HypEVs were more easily taken up and utilized by recipient cells. The MRI results illustrated that the cerebral infarction volume was reduced by 45% with the application of HypEVs, in comparison to the non- HypEV treatment group. Mechanistically, the FUS protein is necessary for the uptake and neuroprotection of HypEVs against ischemic stroke as well as carrying a large amount of mitochondrial mRNA in HypEVs. However, FUS knockdown attenuated the neuroprotective rescue capabilities of HypEVs. Our comprehensive dataset clearly illustrates that FUS-mediated HypEVs deliver exceptional neuroprotective effects against ischemic stroke, primarily through the maintenance of neurite integrity and the reduction of mitochondria-associated apoptosis.

关键词： Hypoxia FUS Neuron-derived small extracellular vesicle Neuroprotection Mitochondrial mRNA

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