自闭症个体道德推理的心理机制及其脑机制

社交障碍是自闭症个体主要的临床症状之一,对他们的道德推理状况进行研究有助于我们解释这一现象.研究表明,自闭症个体在进行道德推理时和常人之间有所不同,而道德推理任务中经常包含有心理理解和移情方面的信息,提示我们自闭症个体的心理推理和移情能力可能是影响他们道德推理的内在心理机制.自闭症个体能够区分道德违背和习俗违背,但是他们经常判断不是故意造成的伤害是有意的.他们对伤害者的情绪线索也不太敏感,不能理解他人的感受,这种移情能力和道德推理能力之间的表现是相关的.此外,自闭症个体对道德推理的解释和言语发展水平之间也存在关联,他们经常通过重复故事情节、引述具体后果来解释道德推理,而缺乏对抽象道德规则的描述.脑成像研究表明,自闭症个体进行道德推理时在眶额叶皮质、杏仁核、脑岛、额下回、前扣带回、内侧前额叶皮质、默认网络模式、右颞顶联合区等部位的激活程度与常人存在着显著差异,这些部位同时也是心理理论或移情能力的重要脑区.自闭症个体在句子加工任务中言语功能联合区的激活程度也与常人存在差异,这可能是他们在对道德推理进行解释时存在困难的内部原因.未来研究需要考察心理理论、移情和言语能力对自闭症道德推理的交互作用,并采取非言语的方式对自闭症个体的道德推理进行研究,同时可通过脑损伤技术和激素水平的分析对影响他们道德推理的生理机制进行更加全面的考察.     

自闭症患者大脑语言功能的异常偏侧化研究进展

自闭症谱系障碍(autismspectrumdisorders,ASD)是一种广泛发展障碍,以社会交往障碍、言语和非言语交流缺陷、兴趣狭窄和行为刻板等为主要临床特征.本文简述了自闭症的核心症状——语言障碍,回顾了自1986年以来,对自闭症语言障碍神经机制的研究,从其大脑结构、功能不对称性及相关利手因素的影响三个方面,综述了自闭症语言功能的异常偏侧化领域的研究成果和进展,期望为自闭症语言障碍的鉴别与治疗提供帮助,并促进汉语背景下自闭症患者的语言功能偏侧化研究.     

基于蛋白质互作网络挖掘自闭症谱系障碍的功能模块与核心基因

自闭症谱系障碍(autism spectrum disorder, ASD)是一种具有高遗传性、临床异质性和生物复杂性的神经行为障碍类疾病。为挖掘ASD发生发展过程中的功能模块与核心基因,本文从自闭症谱系障碍疾病数据库获取ASD相关基因;利用STRING数据库构建ASD相关基因的蛋白质互作网络;通过MCODE算法对蛋白质互作网络进行模块分析并筛选核心基因;最后对各功能模块进行KEGG通路分析,根据富集到的通路类别评估功能模块之间的相互作用。结果显示, 3个疾病基因数据库筛选出182个共有基因,构建的蛋白质互作网络包含171个节点和1 041条边,其中NRXN1、GRIN2B、GRIN2A、DLG4、NLGN3、MECP2、CNTNAP2、BDNF、NLGN4X、FMR1等23个基因具有较高的连通度(degree)。从蛋白质互作网络中分析得到5个功能模块,包括68个核心基因。KEGG富集分析发现功能模块参与多个生物学通路,包括细胞黏附分子、钙离子通路、神经活性的配体-受体相互作用、多巴胺能神经突触等。分析结果提示,挖掘的ASD功能模块和核心基因大多集中在神经元活动、信号分子和信号传导等,且各模块相互作用共同影响ASD的发生发展。     

自闭症儿童口腔正畸治疗中系统性心理预防与干预的作用

目的:评估系统性心理预防及干预在自闭症儿童口腔疾病治疗中的作用。方法:将在我医院进行正畸治疗的40例12~16岁自闭症患者按着随机分配分为对照组与实验组,每组各20例。在正畸治疗过程中,对照组实施常规心理行为预防及干预,包括:治疗前的基础准备、治疗过程中注意事项、治疗后康复方案及辅助治疗等。而对于实验组,除了实施常规的行为预防及干预外,还进行系统性心理行为预防及干预,包括:语言疏导、健康教育、辅助矫正、生命体征监测、肢体语言演示等。结果:实验组和控制组的孩子们能够完成正畸治疗,自闭症儿童治疗配合的的程度,听话依从性,显著高于对照组(P0.01),两组之间蛀牙数和牙龈指数存在差异(P0.05)。结论:系统性行为预防及干预能够提高自闭症儿童的配合合作的程度及医嘱依从性,值得在口腔正畸科门诊自闭症儿童患者中推广。     

自闭症的病因和治疗方法研究进展

自闭症是一种发育障碍类疾病,病程可持续一生,难以逆转,且患病率逐年升高,已给家庭和社会造成巨大的经济和社会负担.然而,自闭症的病因尚未完全明晰,缺少有效的治疗和干预方法.自闭症是生物性疾病,受基因和环境因素共同影响,环境可能是主要影响因素.自闭症儿童大脑早期发育异常可能是自闭症发病的直接诱因,神经毒性物质、营养物质、代谢产物和神经活性物质等都可能是自闭症的病因.一些自闭症患者存在染色体异常和基因变异,同时,更多的病例在胃肠道症状等其他方面也表现异常.自闭症患者中较高比例的胃肠道异常症状与患者肠道微生物紊乱关系密切,因此推论,微生物、肠道与大脑构成的菌-肠-脑轴可能在自闭症的发病过程中起重要作用.针对不同的影响因素,目前,已有多种干预方法,包括生物和非生物疗法.生物疗法包括:抗生素、药物和饮食等,其中,以肠道微生物为靶点的检测与干预的自闭症疗法将是未来的趋势,用益生菌和粪菌移植进行干预也日趋引起关注.虽然,这些疗法都有患者在使用,但多数疗法并不能有效改善自闭症核心症状,仍缺乏完整有效的安全性和有效性评估,因此,今后应加强系统性的控制研究,开展针对菌-肠-脑轴的病因探索和微生物干预研究.     

MMP-1、MMP-3 和MMP-13在慢性睡眠剥夺所致颞下颌关节损伤中的变化

目的：观察MMP-1、MMP-3 和MMP-13 在慢性睡眠剥夺所致颞下颌关节损伤中表达的变化,探讨慢性睡眠剥夺所致颞下颌关节损伤的可能机制。方法：采用改良多平台(MMPM)建立大鼠慢性睡眠剥夺模型,将90 只成年雄性Wastar 大鼠随机分为小平台组、网格组和对照组。小平台组和网格组大鼠接受每天18 h的睡眠剥夺和6 h间歇期(10:00-16:00),间歇期大鼠正常笼养。实验第7、14 和21 d时分别观察动物的行为学观察、检测动物血浆皮质醇(CORT)和促肾上腺皮质激素(ACTH)水平检测,通过免疫印迹法和实时定量聚合酶链反应(PRC)检测颞下颌关节软骨中MMP-1、MMP-3 和MMP-13 的蛋白和mRNA表达,并通过HE 染色法观察颞下颌关节结构的变化。结果：与对照组和网格组大鼠相比,小平台组大鼠第14 d和21 d 时髁突软骨中间部位表面纤维在出现明显的炎症、松解及脱落现象;第21天时的血浆ACTH 和CORT 水平均显著高于网格组和对照组,差异有统计学意义(P<0.05);第7、14、21 d时关节软骨MMP-1 和MMP-13 蛋白和mRNA 的表达水平均显著上调(P<0.05)。结论：慢性睡眠剥夺所致的颞下颌关节损伤可能与关节软骨中MMP-1、MMP-3 和MMP-13 的表达上调有关。     

从中医发展现状和价值角度谈当今中医如何发展

在当今经济全球化的趋势下,先进的科技、学术理论不断的涌现在国内,面对如此的环境,我国中医的发展面临着前所未有的大冲击。无论社会怎么变,我们不可否认的便是历经几千年来的风雪洗礼,我国的中医学独树一帜的流传到了今天。中医文明的生生不息得益于它自身的价值,但是在面对西医如此盛行的境况下,当今的中医虽然有着独特的魅力,可在一定程度上还是敌不过西医的受欢迎程度。在此种境地下,当今中医的发展就显得尤为重要了,本文正是从中医本身的现状和价值来探讨当今中医的走向。     

SARS和MERS中和抗体假病毒检测方法的建立

严重急性呼吸综合征冠状病毒(SARS-CoV)和中东呼吸综合征冠状病毒(MERS-CoV)均属冠状病毒科(Coronaviridae),能够引起人类严重疾病,特别是SARS-CoV可以导致严重急性呼吸综合征,而且容易造成暴发式流行,引起社会恐慌。本研究利用含有SARS-CoV和MERS-CoV棘突蛋白(Spike protein,S)基因的表达质粒pcD-NA3.1-SS、pcDNA3.1-MS,成功构建了高滴度假病毒,在此基础上通过对病毒接种量进行优化,建立了稳定可靠的假病毒中和抗体检测方法,并通过检测SARS恢复期病人血清以及免疫后小鼠血清对方法的特异性、稳定性以及重复性进行分析,充分证明了该方法是有效的血清中和抗体的检测手段。本研究成功构建了不依赖于BSL-3级生物安全条件的SARS和MERS假病毒,不仅可应用于血清中和抗体检测,还为后续单克隆抗体及抗病毒药物筛选和评价、疫苗研发及病毒感染机制研究等奠定了基础。     

云南锦鲤养殖场鲤浮肿病毒的鉴定及基因型分析

锦鲤睡眠病(Koi sleepy disease,KSD)是一种由鲤浮肿病毒(Carp edema virus,CEV)引起鲤科鱼类死亡的病毒性传染病,已经对世界鲤科鱼类养殖业造成危害。2016年,中国云南某锦鲤养殖场养殖的锦鲤出现以体表出血、眼睛凹陷、沉于池底昏睡为主要临床症状的疾病,发病水温为11℃~20℃,累计死亡率30%~50%。从该养殖场不同池塘采集两个样品,使用nested PCR和real-time PCR方法进行实验室诊断。结果表明,两个样品CEV检测结果均为阳性,发病锦鲤鳃和肾脏CEV病毒载量为250.02~1 332.94拷贝/250ng,鳃中CEV病毒载量约为肾脏的6~7倍。在排除寄生虫、细菌、SVCV和KHV感染后,推测CEV可能是引起此次云南锦鲤场发生疫情的病原,但还需回归感染实验做进一步验证。基于CEV P4a基因的遗传进化分析结果表明,此次从云南发病锦鲤检出的两个CEV毒株均属于IIa基因型,且与英国(R083株)和日本CEV毒株(CyPP-3)的遗传进化关系最近。     

δ-睡眠肽与GFP融合蛋白的表达和纯化

构建δ-睡眠肽(DSIP)蛋白与GFP的融合基因表达载体,高效表达和纯化GFP-DSIP融合蛋白。通过SOE-PCR拼接DSIP全长编码基因,并使得DSIP上游具有肠激酶识别位点,经双酶切定向克隆至表达载体pET-28a,构建重组载体pET-28a-DSIP,通过PCR扩增GFP全长编码基因,经双酶切定向克隆至pET-28a-DSIP,构建原核重组表达载体pET-28a-GFP-DSIP,通过双酶切和测序鉴定后,导入E.coli BL21宿主菌中,IPTG诱导表达融合蛋白,采用镍亲和层析和分子筛凝胶层析获得高纯度蛋白,SDS-PAGE分析鉴定。经测序鉴定成功构建了原核重组表达载体pET-28a-GFP-DSIP,在IPTG诱导下获得可溶性的绿色荧光蛋白与睡眠肽的融合蛋白,经Ni-NTA亲和层析纯化成功获得高纯度的融合蛋白。成功构建了DSIP与GFP融合基因的重组表达载体,确定了GFP-DSIP融合蛋白诱导表达的最佳条件,获得了较高纯度的融合蛋白,为进一步研究DSIP蛋白的生物学功能奠定了基础。     

The Use of Stem Cells to Study Autism Spectrum Disorder

Autism spectrum disorder (ASD) affects as many as 1 in 68 children and is said to be the fastest-growing serious developmental disability in the United States. There is currently no medical cure or diagnostic test for ASD. Furthermore, the U.S. Food and Drug Administration has yet to approve a single drug for the treatment of autism’s core symptoms. Despite numerous genome studies and the identification of hundreds of genes that may cause or predispose children to ASD, the pathways underlying the pathogenesis of idiopathic ASD still remain elusive. Post-mortem brain samples, apart from being difficult to obtain, offer little insight into a disorder that arises through the course of development. Furthermore, ASD is a disorder of highly complex, human-specific behaviors, making it difficult to model in animals. Stem cell models of ASD can be generated by performing skin biopsies of ASD patients and then dedifferentiating these fibroblasts into human-induced pluripotent stem cells (hiPSCs). iPSCs closely resemble embryonic stem cells and retain the unique genetic signature of the ASD patient from whom they were originally derived. Differentiation of these iPSCs into neurons essentially recapitulates the ASD patient’s neuronal development in a dish, allowing for a patient-specific model of ASD. Here we review our current understanding of the underlying neurobiology of ASD and how the use of stem cells can advance this understanding, possibly leading to new therapeutic avenues.     

A Comprehensive Survey of Current and Former College Students with Autism Spectrum Disorders

Background: There is a paucity of research concerning individuals with autism spectrum disorders (ASD) pursuing higher education.Method: This study sought to augment this gap in the literature by surveying individuals with ASD who are currently college students or who have previously attended college.Results: Thirty-five individuals completed an online survey. These individuals reported receiving extensive academic supports that enabled their academic success. Their reported difficulties in the social and emotional domains received less support. In addition, not all areas of campus life were supportive, as study abroad and career service offices were reported to not understand individuals with ASD.Conclusions: Overall, the results of this survey indicate the importance of self-advocacy and the need for institutions of higher education to provide comprehensive supports for individuals with ASD in the academic, social, and emotional domains in order to effectively integrate this group into the campus environment.     

Toward Innovative,Cost-Effective,and Systemic Solutions to Improve Outcomes and Well-Being of Military Families Affected by Autism Spectrum Disorder

The burdens faced by military families who have a child with autism are unique. The usual challenges of securing diagnostic, treatment, and educational services are compounded by life circumstances that include the anxieties of war, frequent relocation and separation, and a demand structure that emphasizes mission readiness and service. Recently established military autism-specific health care benefits set the stage for community-viable and cost-effective solutions that can achieve better outcomes for children and greater well-being for families. Here we argue for implementation of evidence-based solutions focused on reducing age of diagnosis and improving access to early intervention, as well as establishment of a tiered menu of services, individualized to the child and family, that fit with the military ethos and system of health care. Absence of this new model of care could compromise the utility and sustainability of the autism-specific benefit.     

Increased Risk of Autism Development in Children Whose Mothers Experienced Birth Complications or Received Labor and Delivery Drugs

Autism spectrum disorder (ASD) is a perplexing and pervasive developmental disorder characterized by social difficulties, communicative deficits, and repetitive behavior. The increased rate of ASD diagnosis has raised questions concerning the genetic and environmental factors contributing to the development of this disorder; meanwhile, the cause of ASD remains unknown. This study surveyed mothers of ASD and non-ASD children to determine possible effects of labor and delivery (L&D) drugs on the development of ASD. The survey was administered to mothers; however, the results were analyzed by child, as the study focused on the development of autism. Furthermore, an independent ASD dataset from the Southwest Autism Research and Resource Center was analyzed and compared. Indeed, L&D drugs are associated with ASD (p = .039). Moreover, the Southwest Autism Research and Resource Center dataset shows that the labor induction drug, Pitocin, is significantly associated with ASD (p = .004). We also observed a synergistic effect between administrations of L&D drugs and experiencing a birth complication, in which both obstetrics factors occurring together increased the likelihood of the fetus developing ASD later in life (p = .0003). The present study shows the possible effects of L&D drugs, such as Pitocin labor-inducing and analgesic drugs, on children and ASD.     

A Laboratory Study of Sleep and Dreaming in a Case of Asperger's Syndrome

Asperger's Syndrome (AS) is a pervasive developmental disorder whose continuity with High-Functioning Autism is still a matter of debate. Clinical observations suggest that patients with AS may present the same sleep disorders as autistic patients, including difficulties in initiating and maintaining sleep as well as poor dream recall. We recorded the sleep of a 25-year-old male patient with AS for two nights using a full EEG montage and compared the second night to that of a group of normal participants. We found low levels of slow wave sleep (SWS: stages 3 + 4), high levels of stage 1, and a large number of awakenings. The organization of REM sleep was unremarkable, including normal REM density. Analyses of phasic EEG events revealed a very low incidence of sleep spindles and a normal number of K-complexes over bilateral frontal and central EEG leads. In order to collect dream reports, the patient was awakened three times over two nights following at least 15 minutes of REM sleep in each case. On each occasion the patient was not aware of any mental activity happening just prior to awakening. These observations are discussed with regards to the connections that may exist between EEG sleep spindle activity, selective attention, and the capacity to generate a dream report.     

Molecular Therapy and Prevention of Liver Diseases

Molecular analyses have become an integral part of biomedical research as well as clinical medicine. The definition of the genetic basis of many human diseases has led to a better understanding of their pathogenesis and has in addition offered new perspectives for their diagnosis, therapy and prevention. Genetically, human diseases can be classified as hereditary monogenic, acquired monogenic and polygenic diseases. Based on this classification, gene therapy is based on six concepts (1) gene repair, (2) gene substitution, (3) cell therapy, (4) block of gene expression or function, (5) DNA vaccination and (6) gene augmentation. While major advances have been made in all areas of gene therapy during the last years, various delivery, targeting and safety issues need to be addressed before these strategies will enter clinical practice. Nevertheless, gene therapy will eventually become part of the management of patients with various liver diseases, complementing or replacing existing therapeutic and preventive strategies.     

骨折电流疗法的改良

目的:针对电流治疗骨折等疾病时存在的问题,提出相应的改进方法。方法:分析以往使用电流对骨折等疾病进行治疗时存在的电化学副作用、创口易于感染、重复施术不便等问题,提出相应的诸如使用溶液导电、隔离电解物、使电极与创口闭合生长等改进方法;并提出将电流治疗与药物治疗相结合的骨科疾病电流疗法改良方案。结果:将电流与药物相结合治疗骨折等疾病是很有可行性的治疗方法,本法不仅克服了已往疗法存在的一些问题,还为骨伤药物直接进入病患部位提供了有效的平台,使骨折、骨不连等疾病能够快速愈合。今后应加强研究骨折愈合各阶段所需的直接注射药物及其配比。完善电流—药物复合电极使用方法,以便与本法尽快进入临床实践。结论:将电流与药物相结合治疗骨折等疾病是很有可行性的治疗方法。     

Antidepressant effects of combination of sleep deprivation and early evening treatment with melatonin or placebo for winter depression

Patients with winter depression (seasonal affective disorder) respond beneficially to sleep deprivation and bright light, but the mechanisms of these responses remain unknown. The study was designed to test whether afternoon/evening melatonin can prevent further relapse after sleep deprivation (presumably due to a pharmacologically induced advance shift of circadian phase). Compared to phase advancing by alteration of sleep - wake schedule or by bright light exposure, the melatonin intake is a more tolerated treatment procedure, and it provides a possibility of blind comparison between chronotherapeutic and placebo treatments. The depression was scored in 16 female patients with winter depression and 17 age-matched female controls before and after total night sleep deprivation and after subsequent six-day administration of melatonin (0.5 mg) or placebo under double blind conditions. The melatonin intake was scheduled at 17:00 in order to produce a phase advance of circadian rhythms. Sleep deprivation resulted in 38% reduction of depression score in patients, but it did not reduce depression score in controls. After subsequent treatment with placebo or melatonin, slight but significant improvement of mood was found in controls. These treatments also stabilized the antidepressant response to sleep deprivation in patients. However, neither differential effect of melatonin and placebo on depression score nor alteration of habitual sleep timing was found in patients and controls. Thus, the study results do not provide evidence for the antidepressant potential of melatonin in patients with winter depression under realistic clinical conditions. The finding of stabilization of mood in patients with placebo points to the contribution of psychological factors to the therapeutic action of this and other types of innovative treatments for winter depression. To include psychosocial aspects in the theoretical framework of seasonal depression, we conceptualized depression as an evolved feature of emotional response to psychosocial rather than physical environment. The seasonality of depression might be explained by cumulative effects of aperiodical psychosocial factors and periodical physical factors on one of the mechanisms of brain neurotransmission.     

用微生态疗法防治幼畜幼禽腹泻和提高增重的试验

本试验用乳酸杆菌K、P株作为幼畜禽的饲料添加剂。对动物试验的结果表明,使哺乳仔猪平均日增重分别比对照组提高17.36％和18.68％,使肉用仔鸡提高增重10.5％;与对照组相比,差异均极显著(P<0.01)。本制剂对预防幼畜禽下痢亦有显著效果。     

The acquisition of conscience and Developmental Systems Theory

Summary Proponents of Developmental Systems Theory (DST) argue that it offers an alternative to current research programs in biology that are built on the historic disjunction between evolutionary and developmental biology. In this paper I illustrate how DST can be used to account for the acquisition of an important component of moral agency, conscience. Susan Oyama, a major proponent of DST, has set moral issues outside the compass of DST. Thus, I examine her reasons for restricting DST to non-moral matters, and argue that they are not decisive. On the positive side, I argue that DST not only is compatible with attempts to describe and explain moral agency but also aids us in understanding it. In particular, I show how DST can provide a fruitful perspective for viewing some significant current findings and theories in moral developmental psychology about the acquisition of conscience. The familiar dichotomies resisted by DST, those between genes and environment, inherited and acquired, innate and learned, and biological and cultural, have also plagued human developmental psychology, including moral development. By bringing a DST perspective to the study of moral development, I illustrate how a DST perspective might offer a promising way to reconceive that phenomenon, and provide some insights into how further work in understanding the development of moral agency might proceed. Thus, I hope to contribute to the current efforts of proponents of DST to integrate developmental and evolutionary considerations.