SORLl基因rs2070045单核苷酸多态性与遗忘型轻度认知功能障碍的关联分析

目的分析北京地区汉族人群分拣蛋白相关受体1（sortilin-relatedreceptorl,SORL1,又称sorl1或LR11）rs2070045单核苷酸多态性与遗忘型轻度认知功能障碍（amnesticmildcognitiveimpairment,aMCI）是否存在关联。方法采用病例对照的关联分析方法,提取139例aMCI（病例组）和213例非认知障碍健康人（对照组）外周血中基因组DNA,应用聚合酶链反应-高分辨溶解曲线（PCR-HRM）技术结合测序验证法检测SORLl基因rs2070045位点单核苷酸多态性的分布情况,分析SORL1基因多态性与aMCI的相关性。结果aMCI组中GG,GT,TT基因型分别为54例（38．8）,65例（46．8）,20例（14．4）;对照组中GG,GT,TT基因型分别为59例（27．7）,103例（48．4）,51例（23．9）。aMCI组与对照组SORL1基因rs2070045单核苷酸多态性的基因型及等位基因频率分布差异明显（X2=7．109,P=0．029;X2=7．315,P=0．007）,男性aMCI组与对照组基因型及等位基因频率分布差异不明显（X2=3．068,P=0．216;X2=2．357,P=0．125）,女性aMCI组与对照组基因型频率分布差异也不明显（X2=4．229,P=0．121）,等位基因频率分布差异明显（x。=4：438,P=0．035）。结论SORL1基因rs2070045位点单核苷酸多态性与北京地区汉族人群aMCI的发生明显相关,G等位基因为危险等位基因。     

血管内皮生长因子基因启动子区多态与散发性阿尔茨海默病的关系

目的 研究血管内皮生长因子(vascular endothelial growth factor,VEGF)基因启动子区多态与散发性阿尔茨海默病(sporadic Alzheimer's disease,SAD)发病的关系.方法 用聚合酶链反应.限制性片段长度多态性(PCR-RFLP)或直接测序的方法对北方汉族279例SAD患者和317名健康对照者进行多态分型.采用SPSS 11.5统计学软件包进行等位基因和基因型分布的比较及其与疾病的关联分析.结果 北方汉族人群中VEGF启动子存在3个多态位点:-2578C/A(rs699947)、-2549I/D(rs35569394)和-1154G/A(rs1570360),其中-2549I/D位点为18个碱基的插入或缺失.-2578C/A和-2549I/D存在显著的连锁不平衡,当-2578为A等位基因时,-2549I/D位点有18个碱基的插入,而当-2578是C纯合子时,-2549I/D位点则为18个碱基的缺失.这3个多态位点的基因型频率、等位基因频率以及单体型分布在SAD患者和对照组间差异无统计学意义.用Logistic回归校正年龄、性别和ApoE状态后,-1154G/A的GG基因型增加了SAD的发病风险.在不携带ApoE ε4的亚组中,单体型-2549D/-1154G可能增加SAD的发病风险(OR=1.325,95%CI1.023～1.716,P=0.033).结论 北方汉族人群中VEGF启动子存在3个多态位点-2578C/A、-2549I/D和-1154G/A.-1154G/A的GG基因型增加了SAD的发病风险.在不携带ApoE ε4的情况下,VEGF启动子的-2549D/-1154G单体型可能是SAD发病的危险因素.     

色氨酸羟化酶2基因多态性与强迫症的关联研究

目的 探索汉族人群中具有中枢特异性的色氨酸羟化酶2(TPH2)基因多态性与强迫症的关系.方法 选取TPH2基因转录区的单核苷酸多态rs4570625,采用TaqMan探针SNP基因分型技术测定137例强迫症患者和190名健康人的多态分布. 结果强迫症组色氨酸羟化酶(TPH)-2基因rs4570625G/T多态基因型及等位基因频数多态分布与对照组间有统计学差异 (χ2=9.972,P<0.01;χ2=8.417,P<0.01); GG基因型和G等位基因与强迫症之间存在显著正关联 [比数比(OR)值分别为2.239和1.587].早发型患者组该多态基因型及等位基因频数多态分布与对照组间有显著差异 (χ2=9.202,P<0.05;χ2=8.833,P<0.01); GG基因型和G等位基因与早发型强迫症之间存在显著正关联[OR值分别为2.514和1.886],晚发型患者组与对照组间无统计学差异. 结论在汉族人群中色氨酸羟化酶TPH2基因rs4570625G/T多态可能与强迫症存在遗传关联,GG基因型和等位基因G可能主要是早发型强迫症的风险因子.     

两种轻度认知损害患者的神经心理学功能比较

背景区别轻度认知损害（mildcognitiveimpairment,MCI）的两种亚型,即遗忘型轻度认知损害（alTlnesticmildcogni—tiveimpairment,aMCI）和小血管型轻度认知损害（MCIassociatedwithsmallvesseldiseases,sv-MCI）将有利于延缓和预防MCI进展为阿尔茨海默病性痴呆和血管性痴呆。目的识别并区分区aMCI与sv-MCI的神经心理学特征。方法从宣武医院神经科门诊就诊患者或在北京社区进行的一项入户调查中选择符合入组标准的被试。根据Pe—tersen诊断标准筛选aMCI患者50例,根据Hachinski诊断标准筛选sv-MCI患者65例。以上两组患者和49名55岁以上没有认知障碍的社区被试一同接受简明精神状态量表（MiniMentalStateExamination,MMSE）检查及画钟测验（ClockDrawingTest,CDT）与听觉词语学习测验（AuditoryVerbalLearningTest,AVLT,评定即刻记忆、延迟回忆和延迟再认能力）。采用单因素方差分析法比较3组被试各项测验的平均得分,如果结果存在明显差异,再进行多个样本两两比较的Tukey法检验。结果aMCI组和SV．MCI组5项测验平均得分均明显低于健康对照组。aMCI组AVLT即刻记忆、延迟回忆和延迟再认测验得分均低于SV．MCI组。在校正了年龄、性别、受教育年限后,上述差异仍旧存在。结论实验结果与既往结果一致,与SV—MCI患者相比,aMCI患者记忆损害更加明显。记忆相关的评估测验,尤其是AVLT,或将有助于区别这两种MCI亚型。     

卷曲蛋白6基因多态性与中国北方汉族儿童神经管缺陷的相关性

目的 研究中国北方汉族儿童卷曲蛋白6基因编码区单核苷酸多态性(singlenucleotide polymorphisms,SNPs)与神经管缺陷(neural tube defects,NTDs)发生的相关性.方法 采用PCR扩增和测序的方法对135例NTDs患儿和135例对照者卷曲蛋白6基因编码区3个错义单核苷酸多态位点(rs827528,rs3808553,rs12549394)进行基因分型及统计学分析.结果 rs3808553等位基因T和基因型TT在病例组中的频率显著高于对照组,T等位基因和TT基因型儿童发生NTDs的危险性分别是G等位基因和GG基因型的1.575倍(OR=1.575,95％CI1.112 ～2.230,P=0.010)和2.811倍(OR =2.811,95％CI 1.325～5.967,P=0.023);其余2个多态位点在两组间等位基因与基因型分布差异不具有统计学意义.3个SNPs位点间的单体型A-G-C在病例-对照组间分布具有统计学意义(OR =0.560,95％CI0.378～0.830,P=0.004),而单体型A-T-C在病例-对照组间分布也具有统计学意义(OR=1.670,95％CI 1.126 ～2.475,P=0.011).结论 中国北方汉族儿童中卷曲蛋白6基因rs3808553位点多态性与NTDs发生具有明显相关性,基因型TT使NTDs发生的危险度增加,而rs827528和rs 12549394位点多态性与NTDs发生无明显相关性.     

不同记忆测验识别轻度认知损害的差异

目的分析不同的记忆测验对于轻度认知损害（MCI）的识别力的差异。方法2004年5月至2006年5月就诊于本院神经内科记忆障碍门诊的被试共712例，除了客观记忆指标，其余要求均符合MCI入组标准的有329例。全部入组者完成听觉词语学习测验（AVLT）、逻辑记忆测验（LM）、Rey-Osterrieth复杂图形测验（CFT）及MMSE、画钟测验、五点测验、言语流畅性测验、Stroop色词测验、连线测验、临床痴呆评定量表。结果对于MCI的识别率AVLT-Ⅱ（51％）〉AVLT-Ⅰ（31％）〉CFT回忆（27％）〉LM-Ⅰ（21％）=LM-Ⅱ（21％）。AVLT-Ⅱ与LM-Ⅱ均〉划界分者，为主观认知缺损（SCI）组，占47％（155／329）；AVLT-Ⅱ与LM-Ⅱ均≤划界分者，为确定MCI组，占19％（63／329）；AVLT-Ⅱ与LM-Ⅱ不一致，其中AVLT-Ⅱ≤划界分而LM-Ⅱ〉划界分者，为分歧组，占32％（104／329）。通过对各领域神经心理测验结果和临床表现进行比较，分歧组明显不同于SCI组，而是接近于确定MCI组，也就是说，分歧组是认知功能损害相对较轻的MCI。结论不同的情景记忆测验对于MCI的识别能力存在巨大的差异。AVLT延迟回忆最敏感，可以作为MCI“记忆减退的客观证据”。     

阿尔茨海默病患者FGF1基因启动子-1385A/G多态与ApoE基因多态关联性分析

目的探讨成纤维细胞生长因子1（FGF1）基因启动子，载脂蛋白E（ApoE）基因多态性在散发性阿尔茨海默病（sporadic Alzheimer disease，SAD）发病机制中的作用。方法应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法检测41例SAD患者和43名健康人中FGF1基因启动子和ApoE基因多态性分布，并通过比值比（OR）对这两种基因与AD之间进行关联性分析。结果FGF1基因启动子多态性（-1385A／G）与AD的发病风险显著相关；GG基因型与非GG基因型的OR=3．15，95％ CI=1．08～5．46。SAD患者与ApoE基因的等位基因ε4正关联，ApoE ε4与非ε4的OR=4．02，95％ CI=1．64～9．52。在ApoE ε4中携带FGF1 GG基因型的OR=15．22，95％ CI=6．68～40．58。结论FGF1基因启动子-1385A／G多态可能是SAD发病的遗传危险因素，FGF1启动子多态与ApoE基因多态性之间有协同作用，ApoE ε4等位基因与FGF1 GG基因型同时存在时，患AD的危险性显著提高。     

遗忘型轻度认知障碍与血管紧张素转换酶的基因多态性和血清水平关系的研究

目的 探讨遗忘型轻度认知障碍(aMCI)与血管紧张素转换酶(ACE)基因插入和缺失(I/D)多态性及血清ACE活力水平的关系.方法 对符合美国Meyo诊所Petersen等制定的aMCI诊断标准的90例aMCI患者(aMC[组)及90名与aMCI组相匹配正常对照者(对照组)进行神经认知功能评估,并应用聚合酶链反应检测ACE基因I/D多态性,用紫外分光光度法检测血清ACE活力水平.结果 (1)aMCI组的各项神经认知测试成绩均差于对照组(P<0.01).(2)aMCI组ACE基因型(χ2=1.510)及等位基因频率(χ2=6.945)与对照组的差异均有统计学意义(P<0.01),其中aMCI组DD基因型(23%)及D等位基因频率(57%)高于对照组(分别为16%和43%).(3)两组DD基因型(n=35)及DI基因趔(n=109)者的听觉词语记忆、符号数宁转换测试、复杂图形及类别词语流畅性得分低于Ⅱ基因型者(n=36;均P<0.05-0.01).(4)aMCI组(F=7.491)和对照组(F=4.970)ACE基因型各亚组问血清ACE活力水平的差异均有统计学意义(P<0.01),两组ACE活力水平均为DD型组>DI型组>II型组.(5)aMCI组血清ACE活力与听觉词语记忆测试的延迟回忆得分呈负相关(r=-0.249,P<0.05).结论 D等位基因可能为aMCI的发病危险因子,其调控的血清ACE高活力水平与aMCI患者情节记忆损害有关.     

载脂蛋白E基因单核苷酸多态性与癫痫耐药的相关性研究

目的探讨汉族人群中载脂蛋白E(apolipoprotein E,Apo E)基因2个单核苷酸多态(single nucleotidepolymorphism,SNPs)位点与癫痫耐药的相关性。方法选取2011年5月-2014年5月期间于我院神经内科癫痫专科门诊患者317例,其中耐药性癫痫患者(耐药组)142例,非耐药性癫痫患者(非耐药组)175例。对入组患者抽取外周静脉血并提取全基因组DNA,对Apo E基因的rs7412与rs769450位点进行基因分型,比较癫痫耐药组与非耐药组患者等位基因频率、基因型频率及位点间连锁不平衡差异。结果与非耐药组比较,耐药组rs769450位点GG基因型(OR=2.041,95%CI 1.195~3.457,P=0.010)和G等位基因(1.619,95%CI 1.191~2.196,P=0.002)的频率较高;两组的rs7412位点在基因型和等位基因频率分布上无明显差异;耐药组rs769450位点GG基因型(OR=2.041,95%CI 1.196~3.557,P=0.011)和G等位基因(OR=1.639,95%CI 1.181~2.185),P=0.003)较高,差异具有统计学意义。通过SHEsis平台对两位点进行连锁不平衡分析,提示rs7412和rs769450位点间不存在连锁不平衡(D’=0.073)。结论 Apo E rs769450 GG基因型及G等位基因在汉族人群中可能与癫痫耐药相关。     

脑源性神经营养因子基因多态性与精神分裂症及其认知功能的关联研究

目的:探讨脑源性神经营养因子(BDNF)基因多态性与中国汉族精神分裂症(SCZ)发病及其认知功能的关系。方法:对354例SCZ患者(SCZ组)和416名健康对照人群(正常对照组)的BDNF基因4个多态性位点(rs7482257、rs7483883、rs1491850、rs16917234)进行基因分型;采用重复性成套神经心理状态测验(RBANS)对SCZ组及正常对照组进行认知功能评估。结果:SCZ组RBANS注意分、言语分、视觉广度分、即刻记忆分、延迟记忆分及总分明显低于正常对照组(F=1. 40,F=16. 38,F=96. 99,F=41. 12,F=114. 40,F=65. 23; P均0. 001)。两组BDNF基因4个多态性位点的等位基因(χ2=0. 37～2. 80)、基因型(χ2=1. 06～5. 77)及单体型(χ2=0. 224～2. 979)分布频率比较差异无统计学意义(P均 0. 05)。在SCZ组中,BDNF基因rs7482257不同基因型间视觉广度因子评分差异有统计学意义(F=3. 79,P=0. 024)。结论:BDNF基因多态性可能与SCZ易感性无关联; BDNF基因rs7482257位点的CC基因型可能与SCZ的视觉广度损害有关。     

The effect of age of onset of PD on risk of dementia

Background Dementia occurs in the majority of patients with Parkinson’s disease (PD). Late onset of PD has been reported to be associated with a higher risk for dementia. However, age at onset (AAO) and age at baseline assessment are often correlated. The aim of this study was to explore whether AAO of PD symptoms is a risk factor for dementia independent of the general effect of age. Methods Two community-based studies of PD in New York (n = 281) and Rogaland county, Norway (n = 227) and two population-based groups of healthy elderly from New York (n = 180) and Odense, Denmark (n = 2414) were followed prospectively for 3–4 years and assessed for dementia according to DSM-IIIR. All PD and control cases underwent neurological examination and were followed with neurological and neuropsychological assessments. We used Cox proportional hazards regression based on three different time scales to explore the effect of AAO of PD on risk of dementia, adjusting for age at baseline and other demographic and clinical variables. Findings In both PD groups and in the pooled analyses, there was a significant effect of age at baseline assessment on the time to develop dementia, but there was no effect of AAO independent of age itself. Consistent with these results, there was no increased relative effect of age on the time to develop dementia in PD cases compared with controls. Interpretation This study shows that it is the general effect of age, rather than AAO that is associated with incident dementia in subjects with PD. Received in revised form: 22 December 2005     

腺垂体功能减退症临床特征变化分析

目的探讨腺垂体功能减退症患者的病因结构变化及临床表现。方法回顾性分析我院2013-01—2016-12住院及门诊78例腺垂体功能减退症患者的临床资料。结果男32例(41.03%),女46例(58.97%);诊断时年龄11~89岁,平均62.5岁;鞍区占位(包括术前及术后)52例(66.67%),席汉综合征8例(10.26%),空泡蝶鞍9例(11.65%),病因不明8例(10.26%),垂体-下丘脑发育不良1例(1.28%)。首次就诊科室:纳差厌食、恶心呕吐就诊于消化内科36例(46.15%)最常见。ACTH+TSH+Gn+G激素缺乏为19例最多,占24.36%,ACTH+TSH+Gn缺乏15例,占19.23%。结论腺垂体功能减退症病因结构发生变化,发病人群、首发症状及受累激素也不同,患者女性多于男性,发病年龄偏高,症状不典型,分布于临床多个科室,其中以低钠血症为首发临床表现就诊消化内科最多。     

Standards of instrumentation of EMG

Standardization of Electromyography (EMG) instrumentation is of particular importance to ensure high quality recordings. This consensus report on “Standards of Instrumentation of EMG” is an update and extension of the earlier IFCN Guidelines published in 1999. First, a panel of experts in different fields from different geographical distributions was invited to submit a section on their particular interest and expertise. Then, the merged document was circulated for comments and edits until a consensus emerged.The first sections in this document cover technical aspects such as instrumentation, EMG hardware and software including amplifiers and filters, digital signal analysis and instrumentation settings. Other sections cover the topics such as temporary storage, trigger and delay line, averaging, electrode types, stimulation techniques for optimal and standardised EMG examinations, and the artefacts electromyographers may face and safety rules they should follow. Finally, storage of data and databases, report generators and external communication are summarized.     

Release of endogenous catecholamines from slices of hypothalamus of rats

The release of endogenous catecholamines from superfused slices of rat hypothalamus was studied under basal conditions and during release evoked by 40 mM K⁺. Catecholamines in superfusates, and in extracts of the tissue after stimulation, were isolated by column chromatography and quantitated by liquid chromatography with electrochemical detection. Norepinephrine (NE) was not consistently demonstrable in superfusate collected under basal conditions, but 40 mM K⁺ caused the release of from 2 to 4 ng/g of tissue per min. The addition of cocaine to the superfusate caused increases in basal and evoked release of NE. Epinephrine (E) could be measured in superfusates of slices from male but not female rats and then only when cocaine was added to the superfusate. Accordingly, the concentration of E in hypothalamus was greater in male rats than in female rats. Dopamine (DA) was not consistently measurable in the spontaneous overflow from slices either in the presence or absence of cocaine. K⁺-evoked release of DA could be demonstrated in slices from female rats. The addition of cocaine increased the evoked release of DA from slices from both sexes. Corticosterone, added to cocaine, had no effects on the efflux of any of the catecholamines. The experiments suggest that neuronal reuptake of all catecholamines is very efficient in the hypothalamus both under basal conditions and during evoked release.     

帕金森病运动症状进展分析

目的分析帕金森病(PD)患者运动症状进展特点。方法采用PD统一评分量表(UPDRS)Ⅲ对912例PD患者进行评估。结果与病程1年的患者比较,除病程1~2年的患者外,其他病程患者的UPDRSⅢ评分、强直分、姿势或步态异常分、轴性症状总分、言语分、步态分显著升高(均P0.05),病程5~6年及14年患者的震颤分,病程5~6年、7~8年、9~13年、14年患者的运动迟缓分、姿势分显著升高(P0.05~0.01)。轴性症状进展速度高于UPDRSⅢ评分。结论 PD患者病程早期UPDRSⅢ评分进展快,震颤症状进展独立于其他症状,轴性症状评分较UPDRSⅢ更敏感地反映疾病加重趋势。     

Effects of prevention of afferentation of the development of the chick optic lobe

BONDY, S. C., M. E. HARRINGTON AND C. L. ANDERSON. Effects of prevention of afferentation on the developmentof the chick optic lobe. BRAIN RES. BULL. 3(5) 411–413, 1978.—The effects of unilateral extirpation of the right optic cup of the three-day incubated chick embryo upon the rate of synthesis and the stability of DNA in the non-innervated optic lobe, have been studied. This surgical procedure prevents innervation of the optic lobe contralateral to the removed eye, while the other optic lobe is normally innervated by retinal ganglion cells of the remaining eye. At the 20th day of incubation, the DNA content of the non-innervated lobe was below that of the paired lobe receiving normal innervation. This deficiency of cell number was caused by two events; death of an excess number of neurons formed early in embryogenesis and a reduced rate of glial proliferation in the later stages of incubation.     

Frequency of accumulation of filaments in adaxonal cytoplasm of Schwann cells of myelinated fibers of rat spinal roots

Summary The frequency of accumulation of 6-nm filaments in the adaxonal cytoplasm of Schwann cells in the 6th lumbar dorsal and ventral roots was evaluated in 4-, 8-, 26- and 45-week-old Sprague-Dawley rats. The frequency was higher in 4- and 8-week-old (growing) rats than in 26- and 45-week old (mature) rats, and also higher in ventral than in dorsal roots in 4-, 8- and 26-week old rats. There were no clusters on certain groups of myelinated fibers according to the size of transverse axonal area, in both the ventral and dorsal roots. Therefore, this accumulation may reflect certain functions of the adaxonal cytoplasm of Schwann cell during natural growth and maturation of the axon and myelin sheath.     

《绵阳市社会心理服务工作管理办法》解读

2018年,国家卫生健康委员会等10部委联合发布《关于印发全国社会心理服务体系建设试点工作方案的通知》,四川省绵阳市被列为全国第一批试点地区。绵阳市人民政府依据《中华人民共和国精神卫生法》等相关法律法规和文件精神,结合前期调查研究和社会心理服务工作的试点实际,编制出台了《绵阳市社会心理服务工作管理办法》,并于2021年12月25日起施行。本文围绕社会心理服务的相关概念、办法总则、重点内容、保障措施等方面进行解读,以期为社会心理服务工作的规范、持续和有效开展提供参考。     

Function of circle of Willis

Nearly 400 years ago, Thomas Willis described the arterial ring at the base of the brain (the circle of Willis, CW) and recognized it as a compensatory system in the case of arterial occlusion. This theory is still accepted. We present several arguments that via negativa should discard the compensatory theory. (1) Current theory is anthropocentric; it ignores other species and their analog structures. (2) Arterial pathologies are diseases of old age, appearing after gene propagation. (3) According to the current theory, evolution has foresight. (4) Its commonness among animals indicates that it is probably a convergent evolutionary structure. (5) It was observed that communicating arteries are too small for effective blood flow, and (6) missing or hypoplastic in the majority of the population. We infer that CW, under physiologic conditions, serves as a passive pressure dissipating system; without considerable blood flow, pressure is transferred from the high to low pressure end, the latter being another arterial component of CW. Pressure gradient exists because pulse wave and blood flow arrive into the skull through different cerebral arteries asynchronously, due to arterial tree asymmetry. Therefore, CW and its communicating arteries protect cerebral artery and blood–brain barrier from hemodynamic stress.     

阿立哌唑对精神分裂症患者生活质量的影响

目的:比较阿立哌唑与利培酮对精神分裂症患者生活质量的影响。方法:60例精神分裂患者随机平分为两组各30例,分别给予阿立哌唑和利培酮治疗。疗程8周。用生活质量综合评定问卷-74(GQOLI-74)、阳性与阴性症状量表(PANSS)及副反应量表(TESS)评定疗效及不良反应。结果:阿立哌唑与利培酮均能显著提高精神分裂症患者生活质量,但阿立哌唑在改善GQOLI-74总分、躯体健康及社会功能维度优于利培酮。结论:阿立哌唑治疗有利于提高精神分裂症患者生活质量。