基于生物信息学技术探索精神分裂症发病的关键基因及诊断的生物标志物

目的 基于生物信息学分析精神分裂症发病的可能分子机制，并分析诊断精神分裂症的生物标志物。方法 选择基因表达综合数据库（GEO）中的GSE48072数据集，对31例精神分裂症患者和35名健康对照者的mRNA表达谱进行生物信息学分析。对筛选得到的差异基因进行功能富集分析。采用string数据库构建差异基因的蛋白-蛋白相互作用（PPI）网络，并通过Cytoscape软件筛选关键基因。关键基因的诊断价值通过受试者工作特征（ROC）曲线验证。结果 共筛选出82个差异基因。富集分析结果显示，差异基因主要集中在炎症、免疫调节和不饱和脂肪酸代谢中。筛选后获得CD244、GZMH、GZMA、KLRD1、GZMK 5个关键基因，ROC曲线下面积分别为0.817、0.725、0.724、0.717、0.693。结论 精神分裂症患者存在炎症通路、不饱和脂肪酸以及维生素代谢异常，CD244等5个相关基因的表达变化可作为精神分裂症发病诊断的生物学标志物。     

高危神经母细胞瘤差异表达基因的生信分析

目的 应用生信分析方法筛选高危神经母细胞瘤的差异表达基因（DEG）。方法 从GEO数据库下载2个高危神经母细胞瘤数据集（GSE49710、GSE73517），筛选DEG，应用GO和KEGG进行富集分析，构建PPI网络筛选中枢基因。结果 GSE49710包括34个上调DEG和284个下调DEG，GSE73517包括62个上调DEG和309个下调DEG。GO分析显示，生物过程主要集中在细胞粘附、GTP酶活性的正调节、转录的负调节、DNA模板化、凋亡过程的负调节、中枢神经系统发育，调节的细胞成分富集在膜的组成部分、细胞外区域、质膜的组成部分、细胞外空间，调节的分子功能富集于钙离子结合、受体结合。KEGG分析显示在可卡因成瘾、造血细胞谱系、NOD样受体信号通路、糖胺聚糖生物合成-硫酸乙酰肝素/肝素中显著富集。PPI网络确定5个中枢基因（ADRB2、MC4R、CD69、RBFOX1和IL7R）。结论 ADRB2、MC4R、CD69、RBFOX1和IL7R可能与高危神经母细胞瘤的发生、发展相关，也可为高危神经母细胞瘤提供潜在治疗靶点。     

颅内动脉瘤破裂关键基因的生信分析

目的 探讨颅内动脉瘤破裂的关键基因.方法 采用生信分析方法,GEO数据库下载数据集GSE13353、GSE15629、GSE54083,R语言筛选差异表达基因(DEG),WGCNA算法分析动脉瘤破裂关键基因,采用GO和KEGG分析关键基因的生物学功能,GSEA软件进行基因富集分析.应用GSE122897数据集进行验证....     

基于GEO数据库筛选垂体泌乳素瘤发生的关键差异基因

目的 利用GEO数据库探究泌乳素瘤发生发展过程中的差异基因及潜在的相互作用机制,为泌乳素瘤的研究和治疗提供新的靶点。方法 挑选GEO数据库GSE119063为研究对象,使用R语言筛选出芯片中的差异基因,利用筛选出的基因进行功能富集分析,构建蛋白质互相作用网络图,探究泌乳素瘤发生发展的相关机制。结果 筛选出泌乳素瘤与正常垂体组织之间的差异基因279个,其中表达上调基因23个,表达下调基因256个。基因本体(gene ontology,GO)富集分析显示,差异基因主要分布于细胞外基质、内质网内腔等细胞结构,主要参与生殖、感官及视觉系统的发育、受体配体活动、生长因子活性、跨膜受体蛋白酪氨酸激酶活性等分子功能。通过对京都基因与基因百科全书(kyoto encyclopedia of genes and genonmes,KEGG)通路富集分析发现,差异基因主要在TGF-β信号通路、干细胞多能性调控信号通路、视黄醇新陈代谢通路等通路上富集。通过蛋白质互相作用网络,进一步挖掘得到可能参与垂体瘤发生发展的20个关键基因,包括SOX2、PAX6、SOX9、POMC等。结论本研究筛选得到SOX2、PAX6、SOX9、POMC等垂体泌乳素瘤发生的关键差异基因,并发现其主要通过影响TGF-β信号通路,从而影响泌乳素瘤的发生发展,可为后续泌乳素瘤的基础研究和治疗提供新靶点。     

阿尔茨海默病的组学机制分析及药物预测

目的通过生物信息学的方法分析阿尔茨海默病(AD)患者和正常对照之间的差异表达基因以及相应的靶向药物。方法从基因表达数据库(GEO)中获取AD患者和正常对照的相关数据芯片(GSE5281),利用R语言LIMMA程序包进行差异表达基因分析,筛选差异表达基因,使用DAVID数据库对进行基因本体(GO)及京都基因与基因组百科全书(KEGG)信号通路富集分析,再利用STRING数据库进行蛋白相互作用网络(PPI)分析,筛选出核心基因和关键基因,以核心基因为靶点的筛选出现有药物。结果共筛选出863个差异表达基因,包括246个上调基因和617个下调基因,GO富集分析结果示差异基因主要功能为ATP结合等,KEGG通路富集分析为帕金森病、朊蛋白病等多种神经退行性疾病,以及长时程增强作用、轴突导向等,STRING数据库分析得到5个核心基因(PSMA7、PSMA3、PSMB7、PSMC5和PSMC3),和31个关键基因(包括23个上调基因和8个下调基因),以核心基因为靶点筛选出8种现有药物,3组基因芯片两两比较筛选出13个共同的差异表达基因。结论基于GEO数据库的生物信息学分析,AD患者与正常对照之间存在差异表达基因并筛选出现有药物。     

基于基因芯片技术研究氯化锂-匹罗卡品致痫小鼠海马组织miRNA-187的表达及GO和KEGG分析

目的基于基因芯片技术研究氯化锂-匹罗卡品致痫小鼠海马组织miRNA-187的表达及GO和KEGG分析。方法选取氯化锂-匹罗卡品致痫小鼠海马组织,采用基因芯片技术挖掘差异基因,并运用q-PCR对芯片结果进行验证,利用Target Scan、miRBase、rna22预测靶基因、DAVID综合分析工具进行GO功能富集分析及KEGG信号通路分析。结果挖掘到与癫痫相关差异基因miRNA-187,利用Target Scan、miRBase、rna22 3种软件预测miRNA-187的靶基因,取交集得到107个共同的靶基因,并进行富集分析得到19个基因功能(P0.05)和7个信号通路(P0.05)。结论通过生物信息学方法,初步分析了miRNA-187在癫痫中可能参与调控的靶基因和信号通路,为下一步实验验证miRNA-187在癫痫的调控机制奠定基础。     

神经干细胞与神经元差异表达基因的生物信息学分析

目的通过生物信息学技术探讨神经干细胞与神经元间基因表达的差异,找出关键的差异基因及其潜在的分子调控机制;并对其所涉及的功能进行分析预测。方法从GEO表达谱数据库中下载与神经干细胞及神经元相关的表达谱基因芯片数据系列GSE70171,导入基因芯片在线分析工具morpheus,筛选出神经干细胞和神经元之间表达差异的基因,并构建聚类分析热图。采用DAVID数据库进行GO功能分析和KEGG通路富集分析,并使用STRING分析与Cytoscape软件构建PPI网络。结果筛选出表达差异的基因有4 022个,其中神经干细胞比神经元上调的基因有2 146个,下调基因1 876个。对表达差异的基因进行的生物信息学分析发现,下调的基因主要与神经元功能相关,上调基因与神经干细胞细胞再生和有肿瘤特征相关,其中神经干细胞的细胞周期通路和癌症通路存在研究价值。结论神经干细胞与神经元之间存在表达差异基因。几个关键基因CDC6、CDKN2A、CDC14A、BUB1、TTK、CHEK1、CDC25C在细胞周期通路中可能与神经干细胞再生功能相关。而KIF23、CDKN2A、TNC、CDC25C、CDCA5、BRCA1可能与神经干细胞的肿瘤特征相关。然而,这些关键基因的功能还需要今后的实验研究进一步证实。     

基于生物信息学技术探索丙戊酸盐导致大鼠孤独症样行为的机制

目的 利用生物信息学技术探索丙戊酸盐导致Wistar大鼠出现孤独症样行为的具体机制。方法 选取SPF级Wistar雄性大鼠4只（300～350 g），雌性大鼠8只（200～250 g），于8～10周将雌、雄大鼠以2︰1的比例合笼过夜。在雌鼠怀孕的第12.5天随机选取4只腹腔注射600 mg/kg的丙戊酸盐，产下的幼鼠纳入丙戊酸盐组，并于幼鼠出生后35 d通过旷场实验、高架十字迷宫实验、新物体识别实验和埋珠实验评价造模是否成功。另随机选取4只孕鼠注射等量生理盐水一次，产下的幼鼠纳入健康对照组。使用GSE42904数据集寻找服用丙戊酸盐和服用甲基纤维素的小鼠脑组织中表达有差异的基因，采用基因本体论（GO）、京都基因与基因组百科全书（KEGG）、GO/KEGG（联合LogFC）以及基因探针富集分析（GSEA）对差异基因进行富集分析。利用实时定量聚合酶链式反应（q-PCR）验证差异基因在丙戊酸盐组幼鼠脑组织中的表达情况。最终纳入丙戊酸盐组幼鼠14只，健康对照组幼鼠7只。结果 在旷场实验中，丙戊酸盐组的中心区累积时间、身体伸直次数少于健康对照组，在新物体识别实验中的识别指数低于健康对照组，埋珠实...     

红花黄色素治疗颅脑损伤作用机制的生物信息学分析

目的 应用生物信息学方法分析红花黄色素（YS）治疗颅脑损伤（TBI）的作用机制。方法 通过GEO数据库查询检索基因表达微阵列芯片数据集GSE21854,筛选差异表达基因（DEGs）, 并与YS靶点基因互相印射取交集。采用DAVID/String数据库对共同靶基因进行GO分析和KEGG通路分析,构建PPI网络。结果 筛选出140个DEGs,与YS靶点基因互相印射后得到26个共同靶基因;进一步GO分析前5个基因功能富集为信号转导、DNA 转录调节、血小板活化、信号与聚集、免疫系统及转录调控区 DNA 结合,KEGG通路途径分析筛选出前5条信号通路包括MAPK信号通路、趋化因子信号通路、PI3K/AKT信号通路、EGFR1信号通路和肿瘤信号通路。PPI分析筛选发现节点最高的中心蛋白编码基因是MAPK3。结论 应用生物信息学方法,可有效获取YS治疗TBI靶向基因的生物学功能、相关信号通路及核心关键蛋白,为后续研究和临床治疗提供了依据。     

基于生物信息学分析筛选重性抑郁障碍关键基因及构建诊断模型

目的 通过整合分析外周血转录组数据探究重性抑郁障碍（major depressive disorder,MDD）关键基因并创建诊断模型。方法 检索基因表达汇编（Gene Expression Omnibus,GEO）公共数据库得到5个MDD外周血相关数据集。使用R limma包及稳健排序聚合（robust rank aggregation,RRA）算法筛选出差异表达基因。以包含最大样本量的GSE98793为训练集，使用Boruta算法进行关键基因筛选，使用logistic回归分析关键基因表达水平与抑郁症的关系。使用Bootstrap法进行内部验证，将剩余4个数据集作为外部验证集，使用受试者工作特征（receiver operating characteristic, ROC）曲线评估诊断模型的诊断性能。结果 分析共得到31个差异表达基因，其中上调基因20个，下调基因11个，从中筛选出7个基因为关键基因，分别为MMP8、TDRD9、FAM3B、LCN2、ARG1、NPTN和FANCF。将7个基因纳入多因素logistic回归分析构建诊断模型，绘制ROC曲线，曲线下面积（area unde...     

Physical and Sexual Abuse and Neglect and Eating Disorder Symptoms

For eating-disordered patients with a history of post-traumatic stress, childhood abuse and neglect, and dissociative disorder, eating behavior symptoms may function as a rational response to unmetabolized traumatic experiences. This paper will review trauma-based theory, dissociation, abreactive, and ego-states therapy as they apply to eating disorder patients.     

Efficacy and Effectiveness of Child and Adolescent Psychotherapy and Pharmacotherapy

Decades of intervention research have produced a rich body of evidence on the effects of psychotherapies and pharmacotherapies with children and adolescents. Here we summarize and critique that evidence. We review findings bearing on the efficacy of psychosocial treatments and medications under controlled experimental conditions. We also report evidence, where available, on the effectiveness of both classes of treatment with clinically referred youth treated in real-world clinical contexts. In general, the large body of evidence on efficacy contrasts sharply with the small base of evidence on effectiveness. Addressing this gap through an enriched research agenda could contribute importantly to linking scientific inquiry and clinical practice—to the benefit of both ventures. This is one element of a multifaceted agenda for future research and for synthesis of research, which will require the interplay of multiple disciplines related to child and adolescent mental health.     

Presence and severity of anorexia and bulimia among male and female Omani and non-Omani adolescents

OBJECTIVE: The population of Oman is a heterogeneous mix of nationalities providing a natural setting for studying the cross-cultural differences in the presence and severity of eating disorders as well as an opportunity for evaluating the performance of measurement instruments for these disorders. METHOD: Disordered eating screening instruments (the Eating Attitude Test and the Bulimic Investigatory Test) were administered to Omani teenagers, non-Omani teenagers, and Omani adults. RESULTS: On the Eating Attitude Test, 33% of Omani teenagers (29.4% females and 36.4% males) and 9% of non-Omani teenagers (7.5% of males and 10.6% females) showed a propensity for anorexic-like behavior. On the Bulimic Investigatory Test, 12.3% of Omani teenagers showed a propensity for binge eating or bulimia (13.7% females and 10.9% males). Among the non-Omani teenagers, 18.4% showed a tendency toward bulimia, with females showing a slightly greater tendency than males. In contrast, barely 2% of Omani adults showed either a presence of or a severity of disorderly behavior with food. CONCLUSION: Omani teenagers scored significantly higher than other ethnic groups and Omani adults. This finding is discussed in the light of emerging evidence from many parts of the world suggesting that cultural transition, compounded by demographic constraints, plays a significant role in abnormal eating attitudes.     

Physical and Sexual Abuse and Neglect and Eating Disorder Symptoms

Abstract

For eating-disordered patients with a history of post-traumatic stress, childhood abuse and neglect, and dissociative disorder, eating behavior symptoms may function as a rational response to unmetabolized traumatic experiences. This paper will review trauma-based theory, dissociation, abreactive, and ego-states therapy as they apply to eating disorder patients.     

Micro-affirmations and Recovery for Persons with Mental Health and Alcohol and Drug Problems: User and Professional Experience-Based Practice and Knowledge

Recurrent factors contributing to a recovery process from co-occurring mental health and addiction problems mentioned by users and professionals have been analyzed as part of working alliances and helpful relationships. Still, we lack knowledge about how helpful relationships are developed in daily practice. In this article, we focus on the concrete construction of professional helpful relationships. Forty persons in recovery and fifteen professionals were interviewed. The interviews were analyzed according to thematic analysis, resulting in three themes presented as paradoxes (1) My own decision, but with the help of others; (2) The need for structures and going beyond them; and (3) Small trivial things of great importance. Micro-affirmations have a central role in creating helpful relationships by confirming the individuals involved as more than solely users or professionals. More attention and appreciation should be paid to practices involving micro-affirmations.

     

Opiate and digitalis receptor assays distinguish between neuroexcitant and inactive organochlorines and between anesthetics and convulsants

Specific binding of [3H]naloxone to rat brain tissue in vitro was inhibited by the excitant organochlorinated insecticides (OCI), by ether (E) and octanol (OCT), and by the convulsant indoklon (IND) and its anesthetic isomer, isoindoklon (ISO). In the presence of 100 mM NaCl the inhibition of naloxone binding by E, OCT and ISO was greatly potentiated, whereas that by OCI and IND was attenuated. KCl (100 mM) was equally effective as NaCl on the action of anesthetics, but the effect of the excitant drugs was, in contrast to NaCl, unaffected by KCl. Specific binding of [3H]ouabain in the absence of Na, was depressed by anesthetics and enhanced by neuroexcitants. In the presence of NaCl, which by itself inhibits ouabain binding to brain, both anesthetics and excitants enhanced ouabain binding. DDE, a non-insecticidal analog of DDT, and the dimethyl derivative of the OCI, lindane, were inactive in the receptor assays. These observations point to a unique isolated system which responds consistently to anesthetic agents as a class and, in a different way, to neuroexcitant compounds.