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A family study of endophenotypes for psychosis within an early intervention programme in Hong Kong: Rationale and preliminary findings

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Chinese Science Bulletin 2011年第32期56卷 3394-3397页

作者： LUI Simon S Y sham.pak CHAN Raymond C K CHEUNG Eric F C Neuropsychology and Applied Cognitive Neuroscience Laboratory Key Laboratory of Mental Health Institute of Psychology Chinese Academy of Sciences Graduate University of Chinese Academy of Sciences Castle Peak Hospital Department of Psychiatry the University of Hong Kong

The study of endophenotypes may be a viable strategy to tackle the genetic complexity and phenotypic heterogeneity of psychosis, but this research direction is relatively under-developed in China as compared to Western countries. We have recently initiated one of the first family studies of endophenotypes for psychosis in China. Patients entering an established early psychosis intervention service are recruited into this research project for phenotyping, endophenotyping and genotyping. At the endophenotypic level, four domains (neurological soft signs, neurocognition of prospective memory, social cognition of facial emotion recognition, and affective cognition of anticipatory and consummatory pleasure) are studied in the sample of patients with psychosis and their unaffected siblings. This article illustrates the benefit of a research-oriented clinical programme and its findings based on the data collected as of early 2011.

关键词：精神病患者稳定家庭早期原理预计香港面部表情识别

Rational use of mesenchymal stem cells in the treatment of autism spectrum disorders

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World Journal of Stem Cells 2019年第2期11卷 55-72页

作者： Qiang Liu Mo-Xian Chen Lin Sun Chloe U Wallis Jian-Song Zhou Li-Juan Ao Qi Li pak C sham Department of Surgery The Chinese University of Hong Kong School of Rehabilitation Kunming Medical University Department of Psychology Weifang Medical University Medical Sciences Division University of Oxford Mental Health Institute of the Second Xiangya Hospital Central South University Department of Psychiatry the University of Hong Kong State Key Laboratory of Brain and Cognitive Sciences Center for Genomic Sciences the University of Hong Kong

Autism and autism spectrum disorders(ASD) refer to a range of conditions characterized by impaired social and communication skills and repetitive behaviors caused by different combinations of genetic and environmental influences. Although the pathophysiology underlying ASD is still unclear, recent evidence suggests that immune dysregulation and neuroinflammation play a role in the etiology of ASD. In particular, there is direct evidence supporting a role for maternal immune activation during prenatal life in neurodevelopmental conditions. Currently, the available options of behavioral therapies and pharmacological and supportive nutritional treatments in ASD are only symptomatic. Given the disturbing rise in the incidence of ASD, and the fact that there is no effective pharmacological therapy for ASD, there is an urgent need for new therapeutic options. Mesenchymal stem cells(MSCs) possess immunomodulatory properties that make them relevant to several diseases associated with inflammation and tissue damage. The paracrine regenerative mechanisms of MSCs are also suggested to be therapeutically beneficial for *** the underlying pathology in ASD, including immune system dysregulation and inflammation, represent potential targets for MSC therapy. This review willfocus on immune dysfunction in the pathogenesis of ASD and will further discuss the therapeutic potential for MSCs in mediating ASD-related immunological disorders.

关键词： Autism spectrum disorders Mesenchymal stem cells Major histocompatibility complex Inflammation Maternal immune activation Cell therapy

The role of gene variants in the pathogenesis of neurodegenerative disorders as revealed by next generation sequencing studies:a review

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Translational Neurodegeneration 2017年第1期6卷 245-255页

作者： Shirley Yin-Yu Pang Kay-Cheong Teo Jacob Shujui Hsu Richard Shek-Kwan Chang Miaoxin Li pak-Chung sham Shu-Leong Ho Division of Neurology Department of MedicineQueen Mary HospitalUniversity of Hong KongHong KongPeople’s Republic of China Centre for Genomic Sciences University of Hong KongHong KongPeople’s Republic of China Department of Medical Genetics Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouPeople’s Republic of China Key Laboratory of Tropical Disease Control(SYSU) Ministry of EducationGuangzhouPeople’s Republic of China

The clinical diagnosis of neurodegenerative disorders based on phenotype is difficult in heterogeneous conditions with overlapping *** does not take into account the disease etiology or the highly variable clinical course even amongst patients diagnosed with the same *** advent of next generation sequencing(NGS)has allowed for a system-wide,unbiased approach to identify all gene variants in the genome *** the plethora of new genes being identified,genetic rather than phenotype-based classification of Mendelian diseases such as spinocerebellar ataxia(SCA),hereditary spastic paraplegia(HSP)and Charcot-Marie-Tooth disease(CMT)has become widely *** has also become clear that gene variants play a role in common and predominantly sporadic neurodegenerative diseases such as Parkinson’s disease(PD)and amyotrophic lateral sclerosis(ALS).The observation of pleiotropy has emerged,with mutations in the same gene giving rise to diverse phenotypes,which further increases the complexity of phenotype-genotype *** mechanisms of pleiotropy include different downstream effects of different mutations in the same gene,presence of modifier genes,and oligogenic *** directions include development of bioinformatics tools and establishment of more extensive public genotype/phenotype databases to better distinguish deleterious gene variants from benign polymorphisms,translation of genetic findings into pathogenic mechanisms through in-vitro and in-vivo studies,and ultimately finding disease-modifying therapies for neurodegenerative disorders.

关键词： Next generation sequencing Neurodegenerative diseases Genetics Pleiotropy

Coagulation factors and the incidence of COVID-19 severity:Mendelian randomization analyses and supporting evidence

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Signal Transduction and Targeted Therapy 2021年第7期6卷 1976-1978页

作者： Yao Zhou Xinyi Qian Zipeng Liu Hongxi Yang Tong Liu Kexin Chen Yaogang Wang pak Chung sham Ying Yu Mulin Jun Li The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics Tianjin Medical UniversityTianjinChina Centre for PanorOmic Sciences-Genomics and Bioinformatics Cores The University of Hong KongHong KongChina National Clinical Research Center for Cancer Tianjin Medical University Cancer Institute and HospitalTianjin Medical UniversityTianjinChina

Dear Editor,The evolving pandemic of coronavirus disease 19(COVID-19),is arousing alarm to public *** to epidemiological and observational investigations,coagulopathy was frequently seen in severe COVID-19 *** coagulation factors such as D-dimer,prothrombin time(PT);von Willebrand factor(VWF),platelet count,and fibrinogen were documented to be important predictors of critically ill patients with COVID-19 in many retrospective observational studies and were substantially discussed before(see Supplementary Notes),yet the causality from specific coagulation factors to the incidence of COVID-19 severity and the underlying mechanism remains elusive.

关键词： severity supporting Notes

Interleukin-18 levels in the hippocampus and behavior of adult rat offspring exposed to prenatal restraint stress during early and late pregnancy

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Neural Regeneration Research 2020年第9期15卷 1748-1756页

作者： Mo-Xian Chen Qiang Liu Shu Cheng Lei Lei Ai-Jin Lin Ran Wei Tomy C.K.Hui Qi Li Li-Juan Ao pak C.sham School of Rehabilitation Kunming Medical UniversityKunmingYunnan ProvinceChina Department of Surgery The Chinese University of Hong KongHong Kong Special Administrative RegionChina Department of Rehabilitation China Resources&WISCO General HospitalWuhanHubei ProvinceChina Department of Rehabilitation Medicine the Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan ProvinceChina Institute of Basic Medicine Shandong Academy of Medical SciencesJinanShandong ProvinceChina Department of Psychiatry The University of Hong KongHong Kong Special Administrative RegionChina State Key Laboratory of Brain and Cognitive Sciences The University of Hong KongHong Kong Special Administrative RegionChina Centre for Genomic Sciences The University of Hong KongHong Kong Special Administrative RegionChina

Exposure to maternal stress during prenatal life is associated with an increased risk of neuropsychiatric disorders, such as depression and anxiety, in offspring. It has also been increasingly observed that prenatal stress alters the phenotype of offspring via immunological mechanisms and that immunological dysfunction, such as elevated interleukin-18 levels, has been reported in cultures of microglia. Prenatal restraint stress(PRS) in rats permits direct experimental investigation of the link between prenatal stress and adverse outcomes. However, the majority of studies have focused on the consequences of PRS delivered in the second half of pregnancy, while the effects of early prenatal stress have rarely been examined. Therefore, pregnant rats were subjected to PRS during early/middle and late gestation(days 8–14 and 15–21, respectively). PRS comprised restraint in a round plastic transparent cylinder under bright light(6500 lx) three times per day for 45 minutes. Differences in interleukin-18 expression in the hippocampus and in behavior were compared between offspring rats and control rats on postnatal day 75. We found that adult male offspring exposed to PRS during their late prenatal periods had higher levels of anxiety-related behavior and depression than control rats, and both male and female offspring exhibited higher levels of depression-related behavior, impaired recognition memory and diminished exploration of novel objects. Moreover, an elevated level of interleukin-18 was observed in the dorsal and ventral hippocampus of male and female early-and late-PRS offspring rats. The results indicate that PRS can cause anxiety and depression-related behaviors in adult offspring and affect the expression of interleukin-18 in the hippocampus. Thus, behavior and the molecular biology of the brain are affected by the timing of PRS exposure and the sex of the offspring. All experiments were approved by the Animal Experimentation Ethics Committee at Kunming Medical U

关键词： behavior depression dorsal hippocampus interleukin-18 prenatal restraint stress recognition memory sex ventral hippocampus

Endophenotypic Strategies for Schizophrenia Research:A Link Between Genetics and Clinical Manifestations

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Endophenotypic Strategies for Schizophrenia Research:A Link ...

An Empirical Analysis of SINO-pak Bilateral Trade Performance ——Based on the Gravity Model of Trade

2009年国际基因组学大会

作者： Raymond C.K.Chan Irving I.Gottesman pak sham R.Walter Heinrichs Neuropsychology and Applied Cognitive Neuroscience Laboratory Institute of PsychologyChinese Academy of Sciences Key Laboratory of Mental Health Institute of PsychologyChinese Academy of Sciences Department of Psychiatry University of Minnesota Department of Psychiatry the University of Hong Kong Genome Research Centre the University of HongKong Department of Psychology York University

＜正＞The identification of genes with large effects that contribute to susceptibilities to neuropsychiatric disorders such as schizophrenia has been not very successful due to the lack of powerful molecular genetic approaches,unlike the state of affairs for type 2 *** possible limitation of these studies is that carriers of vulnerable genotypes may be classified as"normal"unless they exhibit full symptom manifestation as a *** diagnoses are likely to be heterogeneous as not all people with the same diagnosis carry the same susceptibility genes.A new encouraging direction is the identification of endophenotypes,characteristics upstream of symptoms and downstream of genetic polymorphisms,which may be more closely linked to gene expression.A substantial number of studies,especially of at-risk offspring,have suggested that neurocognitive dysfunctions are among the most promising of the candidate *** indicators in schizophrenia have been recognized as among the"target features"through which genetic and non-genetic processes lead to neurointegrative defects that later manifest in neurocognitive ***,aberrant neurological indicators have been suggested as potential endophenotypes in *** this presentation,we will review the substantial evidence for the utility of quantifiable neurological soft signs as potential endophenotypes for schizophrenia spectrum *** for additional research to further elucidate the potential use of neurological soft signs for schizophrenia research are made

关键词： endophenotype schizophrenia neurological soft signs

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An Empirical Analysis of SINO-PAK Bilateral Trade Performanc...

作者： sham SUNDER 南京理工大学

学位级别：硕士

pakistan and China enjoy a cordial relationship over the *** decades-long history of friendly relationship in both countries bore the fruits in the form of pakistan–China free-trade agreement（PCFTA）in 2006 signed in Nov.2006 and effect from July *** primary purpose of the study is to analyses pakistan’s bilateral trade performance and influence of this Free Trade Agreement（FTA）with China and also its FTA partner nations by implementing gravity model of trade in a balanced panel dataset dealing with the period *** model used for the analysis of data which is a typically used tool for the evaluation of bilateral trade activities and also showed to be useful in describing bilateral trade of pakistan with China and with all Free Trade Agreement（FTA）-partner countries by higher values of *** outcomes showed that GDP,trade openness in each country,WTO and the shared border nations positively influenced on pakistan’s bilateral trade with all FTA-partner nations,while distance and inflation showed a negative relation towards trade *** additionally specified that the overall Trade Agreements PTAs impact on bilateral trade of pakistan along with its FTA-partner nations is strongly significant and *** have also estimated enormous pakistan’s trade potential just in case of *** pakistan also can lessen its total trade deficit by deflecting its exports out of traditional or conventional destinations towards China,and it is a market of over millions of *** can be accomplished by boosting private sector of pakistan to improve its business procedures and policies,spend money on innovative work,enhance human capital,look for international quality accreditations,and furthermore meet quality criteria as anticipated by the *** sectors of pakistan,as well as exporters,must take on new steps to increase and maximize the exports to China and to generate sensible equality in the bilateral trading relationshi

关键词： Bilateral Trade Gravity Model Free Trade Agreement Panel Data China and pakistan

Extensive brain structural network abnormality in first-episode treatment-naive patients with schizophrenia:Morphological and covariation study

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Extensive brain structural network abnormality in first-epis...

胎儿期恰逢1959～1961年饥荒的中国成人精神分裂症的发病率

中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Siew E Chua Charlton Cheung Grinne M.McAlonan pak C sham David A Collier Marco Picchioni Stefania Benetti Andrea Mechelli Nicolas Crossley Joseph P.Kambeitz Paul Allen Philip McGuire Department of Psychiatry The University of Hong KongPokfulamS.A.R.China MRC SGDP Centre Institute of PsychiatryKing's College LondonLondon SE5 8AFUK Division of Psychological Medicine and Psychiatry Section of NeuroimagingInstitute of PsychiatryKing's College LondonLondon SE5 8AFUK St Andrew's Academic Centre Institute of PsychiatryKing's College LondonNN1 5BG Department of Psychosis Study Institute of PsychiatryKing's College LondonLondon SE5 8AFUK

＜正＞Objective With a particular focus on putative cortico-striatal-thalamic-cortical（CSTC） networks current study aimed to explore robust gray matter volume（GMV） changes in non-medicated first-episode schizophrenia（FES） *** High-resolution T1-weighted images were obtained using 3.0 Tesla magnetic resonance imaging from 86 first-episode drug-naive schizophrenia patients and 86 healthy controls（CON）.Severity of symptoms in patients was evaluated by using Positive and Negative Syndrome Scale（PANSS）.Fourteen spherical region of interest （ROI） GMV in the CSTC loop were acquired after optimized voxel-based morphometry（VBM） *** of Spherical ROIs and corresponding correlation coefficients were compared between FES and CON *** associations of GMV with PANSS subscale score and symptom dimension scores were also *** GMV reduction was detected in bilateral hippocampus in FES group by VBM *** located in left inferior frontal gyrus（Brodmann’s area 47） and right thalamus（medial dosal nucleus） present GMV *** of ROIs revealed more extensive GMV loss and disassociation between *** Our study support that schizophrenia involves distributed rather than focal pathology and disordered *** analysis could make compensation to VBM and ROI method to uncover more subtle aberrations in regional correlation.

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美国医学会杂志（中文版） 2006年第4期25卷 210-214页

作者： David St Clair Mingqing Xu Peng Wang Yaqin Yu Yourong Fang Feng Zhang Xiaoying Zheng Niufan Gu Guoyin Feng pak sham Lin He 张继志（译） Bio-X Center Shanghai Jiao Tong University Shanghai Institute for Nutritional Sdences Shanghai Institute of Biological Sciences Chinese Academy of Sciences Fourth People＇s Hospital Wuhu Anhui Second People＇s Hospital. Huang Shan Anhui Institute of Population Reseasch Peking University Shanghai Institute of Mental Health Shanghai Department of Psychiatry University of Hong Kong Hong Kong NHGG Shanghai Jiao Tong University Shanghai People＇s Republic of China Department of Mental Health University of Aberdeen Scotland Division of Psychological Medicine Institute of Psychiaby London England 不详

背景：精神分裂症是一种常见的中度精神障碍。子宫内营养缺乏可增大患精神分裂症的危险。其主要依据来自1944～1945年荷兰饥饿冬天（Dutch Hunger Winter）研究，当时食品摄入在短期内极剧下降。这项有关饥荒期间受孕人群的大型队列研... 详细信息

背景：精神分裂症是一种常见的中度精神障碍。子宫内营养缺乏可增大患精神分裂症的危险。其主要依据来自1944～1945年荷兰饥饿冬天（Dutch Hunger Winter）研究，当时食品摄入在短期内极剧下降。这项有关饥荒期间受孕人群的大型队列研究显示，发生精神分裂症的危险增大两倍。目的：确定经受1959～1961年大饥荒的中国人是否有相似的结果。设计、地点及参试者：发生精神分裂症危险的调查于安徽省芜湖地区进行，这是当初受灾最重的地区之一。对饥荒之前、饥荒期间和饥荒以后出生的人群发病率进行比较。芜湖及其周围6个县是由一所精神病院负责的。对1971～2001年所有的精神病病历记录均进行检查。精神分裂症患者的临床和社会人口学资料由对自然灾害暴露情况不知情的研究者摘录。有关饥荒年出生人数和死亡人数的数据是有效可用的，累积死亡率根据以后的人口学调查进行估计。主要观测指标：饥荒的证据已经核实，计算未校正的以及对死亡率进行校正后的发生精神分裂症的相对危险度。结果：安徽省的出生率（每1000人）在饥荒期问降低了约80％，从1958年的28．28降至1959年的20．97、1960年的8．61和1961年的11．06。在饥荒期间出生的人，晚年发生精神分裂症的校正后危险明显增高，从1959年的0．84％增至1960年的2．15％和1961年的1．81％。死亡率校正相对危险在1960年出生者为2．30（95％可信区间，1．99～2．05），1961年出生者为1．93（95％可信区间，1．68～2．23）。结论：我们的调查重复了荷兰不同种族人群的数据，结果显示，出生前遭受饥荒可增高晚年患精神分裂症的危险。

关键词：精神分裂症患者中国成人发病率饥荒胎儿期累积死亡率人口学资料相对危险度种族人群芜湖地区