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Development of Human in vitro Brain-blood Barrier Model from Induced Pluripotent Stem Cell-derived Endothelial Cells to Predict the in vivo Permeability of Drugs

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Neuroscience Bulletin 2019年第6期35卷 996-1010页

作者： Yuan Li Xueying Sun Houfu Liu Liang Huang Guofeng Meng Yu Ding Wenji Su Jiaqi Lu sophie gong Georg C.Terstappen Ru Zhang Wandong Zhang Shanghai Key Laboratory of Signaling and Disease Research Laboratory of Receptor-Based Bio-medicineCollaborative Innovation Center for Brain ScienceSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Platform Technology&Sciences GlaxoSmithKline China R&D CentreShanghai 201203China Neurosciences Therapeutic Area Unit GlaxoSmithKline China R&D CentreShanghai 201203China Human Health Therapeutics Research Centre National Research Council of Canada Faculty of Medicine University of OttawaOttawa K1A0R6Canada

An in vitro blood-brain barrier(BBB) model is critical for enabling rapid screening of the BBB permeability of the drugs targeting on the central nervous *** many models have been developed, their reproducibility and renewability remain a challenge. Furthermore, drug transport data from many of the models do not correlate well with the data for in vivo BBB drug ***-pluripotent stem cell(i PSC) technology provides reproducible cell resources for in vitro BBB ***, we generated a human in vitro BBB model by differentiating the human i PSC(hi PSC) line GM25256 into brain endothelial-type cells. The model displayed BBB characteristics including tight junction proteins(ZO-1,claudin-5, and occludin) and endothelial markers(von Willebrand factor and Ulex), as well as high transendothelial electrical resistance(TEER)(1560 ***2±230 ***2) and c-GTPase activity. Co-culture with primary rat astrocytes significantly increased the TEER of the model(2970 ***2 to 4185 ***2). RNAseq analysis confirmed the expression of key BBB-related genes in the hi PSC-derived endothelial cells in comparison with primary human brain microvascular endothelial cells,including P-glycoprotein(Pgp) and breast cancer resistant protein(BCRP). Drug transport assays for nine CNS compounds showed that the permeability of non-Pgp/BCRP and Pgp/BCRP substrates across the model was strongly correlated with rodent in situ brain perfusion data for these compounds(R2= 0.982 and R2= 0.9973,respectively), demonstrating the functionality of the drug transporters in the model. Thus, this model may be used to rapidly screen CNS compounds, to predict the in vivo BBB permeability of these compounds and to study the biology of the BBB.

关键词： Blood-brain barrier Drug transport Induced pluripotent stem cell Cell differentiation Prediction of in vivo permeability

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Identification of Markovian open system dynamics for qubit systems

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Chinese Science Bulletin 2012年第18期57卷 2242-2246页

作者： ZHOU WeiWei SCHIRMER sophie gong ErLing XIE HongWei ZHANG Ming Department of Automatic Control College Mechatronics and AutomationNational University of Defense TechnologyChangsha 410073China Department of Applied Mathematics and Theoretical Physics University of CambridgeWilberforce RoadCB3 OWAUK Physics Department College of ScienceSwansea UniversitySingleton ParkSwanseaSA2 8PPUK

We discuss the problem of identification of the dynamical generators for open two-level quantum systems in a Markovian *** on Bloch sphere representation,the identification problem is converted to the estimation of a 3-dimensional real process matrix A and an inhomogeneous term *** parameter identifiability and sufficient conditions for completely identification of A and c are *** discussion shows that the obtained sufficient conditions are not always *** approach can be generalized to finite-level open quantum systems in an arbitary Markovian environment.

关键词：系统动力学量子位量子系统马氏环境问题转换充分条件参数辨识环境系统

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Incidence and clinical correlates of anger attacks in Chinese patients with obsessive-compulsive disorder

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2019年第4期20卷 363-370页

作者： Ying-ying ZHANG Heng-fen gong Xiao-li ZHANG Wen-juan LIU Hai-yan JIN Fang FANG sophie SCHNEIDER Elizabeth MCINGVALE Chen-cheng ZHANG Wayne K.GOODMAN Xi-rong SUN Eric A.STORCH Department of Functional Neurosurgery Ruijin Hospital Shanghai Jiao Tong University School of Medicine Department of Psychiatry Pudong New District Mental Health Center The People's Hospital of Leshan Department of Psychological Medicine Zhongshan Hospital Fudan University Department of Psychiatry Ruijin Hospital Shanghai Jiao Tong University School of Medicine Department of Psychotherapy Shanghai Hongkou Mental Health Center Menninger Department of Psychiatry and Behavioral Sciences Baylor College of Medicine

Objective: Anger attacks have been observed in patients with obsessive-compulsive disorder(OCD), often triggered by obsessional triggers. However, few studies have reported the clinical characteristics and correlates of anger attacks among Chinese patients with OCD. Methods: A total of 90 adults with a primary diagnosis of OCD, ranging from 15 to 78 years old, participated in the study. Participants were administered the Rage Outbursts and Anger Rating Scale(ROARS), Yale-Brown Obsessive-Compulsive Scale-Second Edition, and Brown Assessment of Beliefs Scale by a trained clinician. Patients completed the Obsessive-Compulsive Inventory-Revised and Depression Anxiety Stress Scale-21. Results: A total of 31.3% of participants reported anger outbursts in the past week, and ROARS scores had no significant correlation with age, duration of illness, OCD severity, depression, or stress. However, ROARS scores were negatively related to education level, and positively related to obsessing symptoms and anxiety. Conclusions: These data suggest that anger attacks are relatively common in Chinese patients with OCD. The severity of anger attacks is related to educational level, obsessing symptoms, and anxiety, which may be a latent variable reflecting executive functioning and emotion regulation skills.

关键词： Obsessive-compulsive disorder Anger attacks Assessment China

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MY RESEARCH ACHIEVEMENTS IN THE FIELD OF NEURO-ANATOMY

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Bulletin of the Chinese Academy of Sciences 1995年第3期9卷 275-276页

作者： Ju gong(The PLA Fourth Military Medical University, Xi’an)

In 1929, I was born in Shanghai. I graduated from the former Hsiang Ya Medical College (a Yale-affdiated medical school in China before Liberation in 1949, and the predecessor of today’s Hunan Medical University) in 1952. My aspiration to be a clinical doctor was strongly influenced by my father sophie (his pen name) whereas my devotion for all my life to neuro-anatomy resulted from the interaction between the mandatory system of work assignment by the State and my personal selfdevelopment. In the year of my graduation, the Ministry of Public Health under the National Military Commission was in need of a human anatomy lecturer and asked its civil counterpart to select a nominee for the vacancy. At the time, Ihad chosen basic medical research as my career and anatomy was definitely not one of my options, nor was any of my classmates in favor of it. However, the solution to this issue was simple enough: the

关键词： MY RESEARCH ACHIEVEMENTS IN THE FIELD OF NEURO-ANATOMY

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