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.     

补体C3基因rs7951位点多态性与重症肌无力的相关性研究

目的 探索补体C3基因rs7951位点多态性与重症肌无力(MC)的易感性和严重程度的相关性.方法 纳入475例MG患者和487例健康对照组,采用SNPscanTM多重SNP分型技术对C3基因rs7951位点进行基因分型,比较等位基因和基因型频率在MG组及各亚组(性别、发病年龄、胸腺情况、首发受累范围以及最严重时的Osserman分型和Osterhuis评分)间的分布.结果 rs7951位点检测到CC、CT、TT3种基因型,MG组T等位基因(118/950,12.4％)高于对照组(92/974,9.4％),差异有统计学意义(P=0.036,OR=1.360,95％ CI 1.019～1.815).分别在共显性、隐性、显性和加性模型下分析MG组与对照组的基因型频率,发现基因型差异(与CC相比)在显性模型(P =0.044,OR=1.38,95％CI1.01 ～1.89)和加性模型(P=0.037,OR =1.36,95％CI 1.02 ～ 1.82)下有统计学意义.除了在15 ～50岁MG亚组与对照组之间,rs7951位点的基因型在其他各MG亚组分布频率的差异无统计学意义.结论 补体C3基因rs7951T等位基因可能与MG易感性相关.     

PentaD、PentaE基因座基因频率在军人主、被动攻击行为群体分布的比较

目的通过比较PentaD、PentaE基因座等位基因及基因型频率在军人主、被动攻击行为群体中的分布,来推测与主、被动攻击行为发生相关的遗传因素。方法采用PCR结合毛细管电泳的方法对华东地区273例男性军人主动攻击行为者与163例男性军人被动攻击行为者进行PentaD、PentaE基因座的基因型分析,观察两组在PentaD、PentaE基因座的等位基因及基因型分布差异。结果PentaD、PentaE基因座均符合Hardy-Weinberg平衡;PentaE基因座基因型频率在主、被动军人攻击行为群体分布差异有统计学意义（P〈0．01）;单因素分析显示两组在PentaE基因座的基因型16-18的频率分布差异有统计学意义（P=0．0001）;PentaE基因座等位基因频率及PentaD基因座等位基因频率和基因型频率在两个群体中分布差异均无统计学意义（P〉0．05）。结论PentaE基因座可能与攻击行为的发生有关;在人攻击行为群体中PentaE基因座的基因型16-18为被动攻击行为的易感因素。     

D6S1043、D12S391基因座与主动攻击行为的关联研究

目的 探讨主动攻击行为与D6S1043、D12S391基因座等位基因或基因型的关联情况.方法 采用PCR结合毛细管电泳的方法对江苏地区103例男性主动攻击行为者(研究组)和159例健康男性(对照组)的外周静脉血样进行D6S1043、D12S391基因座的基因型分析,观察两组在D6S1043、D12S391基因座的等位基因及基因型分布差异,以推测与主动攻击行为相关的易感因素和(或)抗性因素.结果 D6S1043、D12S391基因座均符合遗传平衡定律(Hardy-Weinberg定律)(P＞0.05);在两个群体中D6S1043基因座的基因型12-19的频率分布差异有统计学意义(P =0.000 4,OR=7.511,95％CI:2.084 ～ 27.066),但等位基因频率分布无差异(P ＞0.05/n);在D12S391基因座上未发现分布存在显著差异的等位基因及基因型(P ＞0.05/n).结论 D6S1043基因座的基因型12-19可能为主动攻击行为的易感因素.     

环指蛋白213基因多态性与中国汉族成人型烟雾病遗传易患性的相关性

目的 探讨环指蛋白213(RNF213)基因rs112735431和rs138130613两位点多态性与中国汉族成人型烟雾病的遗传易患性的关系.方法 从南京卒中注册系统中提取2010年12月至2011年10月经脑血管造影明确诊断的64例成年型烟雾病患者,同时选取96名性别和年龄与烟雾病患者相匹配的健康人作为对照.通过改进的多重连接酶检测反应技术分析RNF213基因rs112735431和rs138130613位点的多态性,对各位点基因型、等位基因型频率进行比较分析.结果 病例组中rs112735431位点GA+AA基因型频率为10.94％(7/64)、GG基因型频率为89.06％(57/64),等位基因A频率为6.25％ (8/128)、等位基因G频率为93.75％ (120/128)；对照组分别为1.04％(1/96)、98.96％(95/96),0.52％ (1/192)、99.48％ (191/192),两组间差异具有统计学意义(OR=11.67,95％ CI 1.40 ～97.28,P =0.007;OR=12.73,95％ CI 1.57 ～ 103.09,P=0.003).rs138130613位点的基因型和等位基因频率在两组间差异无统计学意义.结论 RNF213基因rs112735431位点的多态性可能是中国汉族成人型烟雾病患者的易患因子.     

色氨酸羟化酶基因多态性与精神分裂症的关联研究

目的探讨中国汉族人群色氨酸羟化酶(TPH)基因A218C多态性与精神分裂症的关系。方法选取符合美国精神障碍诊断与统计手册第4版(DSM-IV)精神分裂症诊断标准的患者212例和正常对照168名,应用聚合酶链式反应(PCR)扩增及限制性片段长度多态性(RFLP)技术检测TPH基因A218C多态性,比较两组基因型和等位基因频率。结果TPH基因的A218C多态性基因型和等位基因频数在患者组与对照组间的分布差异无统计学意义(P>0.05)。②女性患者等位基因A频率显著高于女性对照组(χ2=4.905,P=0.027,OR=1.637,95%CI:1.057~2.536)。③早发型与晚发型分裂症间基因型和等位基因频率的差异无统计学意义(P>0.05)。④患者组家族史阴性和阳性亚组间的A218C多态性的基因型和等位基因频率的差异无统计学意义(P>0.05)。结论TPH基因A218C多态性等位基因A可能是女性精神分裂症的危险因子。     

P-选择素基因S290N和P-选择素糖蛋白配体-1基因M62I多态性与缺血性脑梗死临床关联性研究

目的探讨P-选择素(SELP)基因S290N和P-选择素糖蛋白配体-1(PSGL-1)基因M62I多态性与缺血性脑梗死的关系。方法选取148例缺血性脑梗死患者作为脑梗死组,并分为大动脉粥样硬化性(LAA)亚组、心源性脑栓塞(CE)亚组和小动脉闭塞性(SAO)亚组;88例正常人群作为正常对照组。运用基因测序方法检测所有受试者SELP基因S290N和PSGL-1基因M62I的基因多态性。结果与正常对照组比较,脑梗死组及其亚组S290N基因型和等位基因频率差异无统计学意义(均P0.05);脑梗死组M62I基因型和等位基因频率差异有统计学意义(均P0.01);LAA亚组M62I基因型差异无统计学意义(χ~2=5.889,P=0.053),但等位基因频率差异有统计学意义(χ~2=6.156,P=0.021);CE亚组基因型和等位基因频率差异均无统计学意义(χ~2=1.693,P=0.429;χ~2=1.372,P=0.238);SAO亚组基因型和等位基因频率差异均有统计学意义(χ~2=12.572,P=0.002;χ~2=8.736,P=0.004)。S290N与缺血性脑梗死风险无相关性(均P0.05)。M62I显性模型和超显性模型与缺血性脑梗死风险有相关性(OR=2.662,95%CI:1.531~4.630,P=0.000;OR=0.392,95%CI:0.219~0.701,P=0.001),而隐性模型和加性模型与缺血性脑梗死风险无相关性(OR=1.428,95%CI:0.528~3.862,P=0.630;OR=2.121,95%CI:0.766~5.872,P=0.156)。结论 PSGL-1基因M62I多态性与缺血性脑梗死之间具有相关性。     

云南纳西族脑梗死患者载脂蛋白E基因多态性的研究

目的 探讨云南纳西族脑梗死患者载脂蛋白E (ApoE)基因多态性.方法 采用基因测序法,对云南58例纳西族脑梗死患者(脑梗死组)和50名纳西族健康对照者(正常对照组)的ApoE基因进行检测.对两组基因型及等位基因频率进行比较.结果 脑梗死组ApoE基因ε3/ε4基因型频率显著高于正常对照组,ε3/ε3基因型频率显著低于正常对照组(均P＜0.05).脑梗死组ApoE基因ε4等位基因频率显著高于正常对照组;ε3等位基因频率显著低于正常对照组(均P＜0.05).相关性分析显示,ApoE基因ε3/ε3基因型及ε3等位基因是脑梗死的保护性因素(OR=0.346,95％ CI:0.176 ～0.681,P=0.020;OR=0.412,95％ CI:0.227 ～0.749,P=0.004),ApoE基因ε3/ε4基因型及ε4等位基因是脑梗死的易感因素(OR =3.818,95％CI:1.509 ～9.665,P=0.005; OR=3.502,95％CI:1.524～8.047,P=0.003).结论 ApoE基因ε3/ε4基因型及ε4等位基因是云南纳西族人群脑梗死的遗传易感因子.     

肿瘤坏死因子超家族成员4基因SNP rs3861950与脑梗死

目的 探讨肿瘤坏死因子超家族成员4(TNFSF4)基因SNP rs3861950与本地区脑梗死发病的关系.方法 采用TaqMan-PCR方法检测TNFSF4基因SNP rs3861950基因型与等位基因频率.湖南籍汉族脑梗死共287例,对照组为湖南籍汉族健康体检者共285名.结果 脑梗死组CC基因型(7.7%)分布与对照组(2.1%)相比,差异具有统计学意义(X2=9.553,P=0.008);C等位基因频率脑梗死组(0.190)高于对照组(0.137,X2=5.887,P=0.015).动脉血栓性脑梗死亚组与对照组比较其基因型(X2=9.396,P=0.009)及等位基因频率(X2=6.134,P=0.013)差异均有统计学意义.非条件Logistic多因素回归分析显示CC基因型使脑梗死发病的风险是其他危险因素的3.7倍(P=0.002,OR 3.706).结论 TNFSF4基因rs3861950 C→T与湖南籍汉族脑梗死发病相关,尤其与动脉血栓性脑梗死发病相关,rs3861950 C等位基因可能是湖南籍汉族脑梗死发病的独立危险因素.     

男性冲动攻击行为的15个短串联重复序列基因位点等位基因频率的病例对照研究

背景：遗传多态性短串联重复序列（short tandem repeats, STRs）分析是用于检测基因型和表型之间关联的公认方法,但它以前没有在冲动攻击行为的遗传学研究中使用。 目的：在有冲动攻击行为史的男性和无冲动攻击行为史的男性对照组之间,比较15个STR基因位点（D8S1179, D21S11, D7S820, CSF1PO, D3S1358, TH01, D13S317, D16S539, D2S1338, D19S433, vWA, TPOX, D18S51, D5S818和FGA）不同多态性的发生率。 方法：应用AmpFlSTR？Identifiler？试剂盒比较407个有冲动性攻击行为的案例和415个对照的15个STR基因位点等位基因的分布。 结果：有冲动攻击行为史的男性以下等位基因的平均频率显著低于对照组：TH01的等位基因10（OR=0.29,95%CI=0.16-0.52, p 结论：据我们所知,本项行为遗传学研究首次清楚表明了特定的遗传标记与非精神病罪犯的冲动暴力行为之间的密切关系。进一步的前瞻性工作将需要确定已辨识出的等位基因是否可以被认为是冲动攻击行为的危险因素以及导致这种关系的基本机制。     

Ultrastructure of non-myelinated neurons during energy deprivation

Summary This paper examines the neuropathology of oxygen-glucose deprivation uncomplicated by stagnant conditions. Rabbit vagus nerves were pulled into asmulti-compartment perfusion chamber, stimulated five times per second and deprived of energy by substituting nitrogen and deoxyglucose for oxygen and glucose in the Locke's perfusate. After incubation the compartments were perfused with gluteraldehyde solution, and the nerves were prepared for electron microscopy. Fixation in the compartments ensured precise cross and longitudinal sections which permitted quantitative comparisons. Although the action potentials ceased in 45 min, 1 h of energy deprivation did not significantly affect the ultrastructure. After 2 h of deprivation the axons were smaller and flattened and microtubules appeared packed together. In the smallest axons the microtubules were gone, the neurofilaments were compacted and the few mitochondria had a dense, homogenous appearance. By 4 h the shrinking was extreme, yet 8% were swollen much larger than any of the controls. Longitudinal views showed these balloned areas were greatly expanded regions of the smallest axons. Both tiny and huge regions were devoid of microtubules and the swollen axons contained expanded mitochondria.Calcium is indirectly implicated in the pathogenesis by the concurrence of mitochondrial alteration as the microtubules disappear coupled with the known role of mitochondria in calcium regulation and the reported effect of high calcium on microtubual dissociation. In is suggested that axons first shrink as osmotially active molecules are used or washed out. After a time without energy the mitochondria can no longer regulate the intracellular calcium, microtubules dissociate, and calcium-activated phospholipases create osmotically active molecules. Finally, high-amplitude, disruptive swelling occurs.Supported, in part, by a Grant-in-aid from the American Heart Association with funds contributed by the American Heart Association, Kansas Affiliate and by the University of Kansas Biomedical Sciences Support Grant RR0737     

星形胶质细胞对天冬氨酸特异性半胱氨酸蛋白酶介导β淀粉样蛋白早期突触毒性作用的影响

目的探讨星形胶质细胞(astrocyte,AS)对天冬氨酸特异性半胱氨酸蛋白酶(cysteinyl aspartate specific proteinase,caspase)介导β淀粉样蛋白(β-amyloid,Aβ)早期突触毒性作用的影响,以期为进一步研究与血管性痴呆(vascular dementia,Va D)的发病机制奠定基础。方法以原代培养大鼠海马纯神经元体系(NE-S)及混合培养体系(MIX-S,主要包含神经元及AS)为研究对象,各体系分为6组:对照组、caspase-8抑制剂组、caspase-9抑制剂组、Aβ处理组、caspase-8抑制剂预处理加Aβ组和caspase-9抑制剂预处理加Aβ组。免疫荧光检测各组近胞体10μm段树突中突触后密度蛋白(postsynaptic density-95,PSD95)表达量的变化。结果 1在NE-S与MIX-S中,与对照组相比,caspase-8抑制剂组、caspase-9抑制剂组PSD95的表达量均无明显差异,Aβ处理组PSD95的表达量均显著降低(P均0.001)。2在NE-S中,与Aβ处理组相比,caspase-9抑制剂预处理加Aβ组PSD95的表达量显著回升至对照组水平,caspase-8抑制剂预处理加Aβ组则无显著改变;在MIX-S中的结果则相反,即caspase-8抑制剂预处理加Aβ组PSD95的表达量显著回升至对照组水平,而caspase-9抑制剂预处理加Aβ组则无显著改变。3MIX-S与NE-S两种培养系统间相比较,对照组间及Aβ处理组间PSD95的表达量均无显著差异,而caspase-8抑制剂预处理加Aβ组间及caspase-9抑制剂预处理加Aβ组间PSD95的表达量差异有显著性。结论在Aβ早期突触毒性作用中,AS参与caspase-8介导的死亡受体通路激活过程,且参与抑制神经元的线粒体通路。     

Effects of genistein on neuronal apoptosis, and expression of Bcl-2 and Bax proteins in the hippocampus of ovariectomized rats

Genistein is one of several isoflavones that has a structure similar to 17β-estradiol, has a strong antioxidant effect, and a high affinity to estrogen receptors. At 15 weeks after ovariectomy, the expression of Bcl-2 in the hippocampus of rats decreased and Bax expression increased, with an obvious upregulation of apoptosis. However, intraperitoneal injection of genistein or 17β-estradiol for 15 consecutive weeks from the second day after operation upregulated Bcl-2 protein expression downregulated Bax protein expression, and attenuated hippocampal neuron apoptosis. Our experimental findings indicate that long-term intervention with genistein can lead to a decrease in apoptosis in hippocampal neurons following ovariectomy, upregulate the expression of Bcl-2, and downregulate the expression of Bax. In addition, genistein and 17β-estradiol play equal anti-apoptotic and neuroprotective roles.     

Magnetic resonance morphometry of the loss of gray matter volume in Parkinson’s disease patients

Voxel-based morphometry can be used to quantitatively compare structural differences and functional changes of gray matter in subjects.In the present study,we compared gray matter images of 32 patients with Parkinson’s disease and 25 healthy controls using voxel-based morphometry based on 3.0 T high-field magnetic resonance T1-weighted imaging and clinical neurological scale scores.Results showed that the scores in Mini-Mental State Examination and Montreal Cognitive Assessment were lower in patients compared with controls.In particular,the scores of visuospatial/executive function items in Montreal Cognitive Assessment were significantly reduced,but mean scores of non-motor symptoms significantly increased,in patients with Parkinson’s disease.In addition,gray matter volume was significantly diminished in Parkinson’s disease patients compared with normal controls,including bilateral temporal lobe,bilateral occipital lobe,bilateral parietal lobe,bilateral frontal lobe,bilateral insular lobe,bilateral parahippocampal gyrus,bilateral amygdale,right uncus,and right posterior lobe of the cerebellum.These findings indicate that voxel-based morphometry can accurately and quantitatively assess the loss of gray matter volume in patients with Parkinson’s disease,and provide essential neuroimaging evidence for multisystem pathological mechanisms involved in Parkinson’s disease.     

Development of 18F-labeled radiotracers for neuroreceptor imaging with positron emission tomography

Positron emission tomography (PET) is an in vivo molecular imaging tool which is widely used in nuclear medicine for early diagnosis and treatment follow-up of many brain diseases. PET uses biomolecules as probes which are labeled with radionuclides of short half-lives, synthesized prior to the imaging studies. These probes are called radiotracers. Fluorine-18 is a radionuclide routinely used in the radiolabeling of neuroreceptor ligands for PET because of its favorable half-life of 109.8 min. The delivery of such radiotracers into the brain provides images of transport, metabolic, and neurotransmission processes on the molecular level. After a short introduction into the principles of PET, this review mainly focuses on the strategy of radiotracer development bridging from basic science to biomedical application. Successful radiotracer design as described here provides molecular probes which not only are useful for imaging of human brain diseases, but also allow molecular neuroreceptor imaging studies in various small-animal models of disease, including genetically-engineered animals. Furthermore, they provide a powerful tool for in vivo pharmacology during the process of pre-clinical drug development to identify new drug targets, to investigate pathophysiology, to discover potential drug candidates, and to evaluate the pharmacokinetics and pharmacodynamics of drugs in vivo.     

Differential expression of carboxyl terminal derivatives of amyloid precursor protein among cell lines.

Understanding the pathway for amyloid percursor protein (APP) catabolism has become an important line of investigation. APP is a ubiquitous membrane bound protein that is rapidly cleaved at the membrane, yielding a secreted protein identical to protease nexin II and an internalized 11.5 kDa 100 residue C terminal derivative (CTD). The levels of CTDs in a variety of cell lines have been examined and were found to differ. Cell types associated with the pathology of Alzheimer's disease (AD), such as olfactory neuroblasts (ON) and cortical vascular endothelial cells, have higher levels of CTDs than lymphoblasts and melanoma cells. The mechanism of CTD catabolism appears to involve the lysosome because blockade of lysosomal but not endosomal or mitochondrial function results in increased levels of CTDs. Under these conditions, production of larger, amyloidogenic CTDs is also seen. In cells possessing higher levels of CTDs we find that the mechanism for production of amyloidogenic CTDs may involve the internalization of intact full-length APP. Thus, inhibition of the lysosomal system appears capable of generating amyloidogenic peptides. The amount of amyloidogenic peptides appears to vary among cell lines. Such variation may shed light on why amyloid accumulates around specific cell types such as vascular endothelial cells, neurons, and glia. Finally, disfunction of the lysosomal system may play a role in the pathogenesis of Alzheimer's disease.     

Neuroprotective role of fibronectin in neuron-glial extrasynaptic transmission

Most hypotheses concerning the mechanisms underlying Parkinson’s disease are based on altered synaptic transmission of the nigrostriatal system.However,extrasynaptic transmission was recently found to affect dopamine neurotransmitter delivery by anisotropic diffusion in the extracellular matrix,which is modulated by various extracellular matrix components such as fibronectin.The present study reviewed the neuroprotective effect of fibronectin in extrasynaptic transmission.Fibronectin can regulate neuroactive substance diffusion and receptor activation,and exert antineuroinflammatory,adhesive and neuroprotective roles.Fibronectin can bind to integrin and growth factor receptors to transactivate intracellular signaling events such as the phosphatidylinositol 3-kinase/protein kinase B pathway to regulate or amplify growth factor-like neuroprotective actions.Fibronectin is assembled into a fibrillar network around cells to facilitate cell migration,molecule and ion diffusion,and even drug delivery and treatment.In addition,the present study analyzed the neuroprotective mechanism of fibronectin in the pathogenesis of Parkinson’s disease,involving integrin and growth factor receptor interactions,and discussed the possible therapeutic and diagnostic significance of fibronectin in Parkinson’s disease.     

Clinical and molecular research of neuroacanthocytosis

Neuroacanthocytosis is an autosomal recessive or dominant inherited disease characterized by widespread, non-specific nervous system symptoms, or spiculated "acanthocytic" red blood cells. The clinical manifestations typically involve chorea and dystonia, or a range of other movement disorders. Psychiatric and cognitive symptoms may also be present. The two core neuroacanthocytosis syndromes, in which acanthocytosis is atypical, are autosomal recessive chorea-acanthocytosis and X-linked McLeod syndrome. Acanthocytes are found in a smaller proportion of patients with Huntington’s disease-like 2 and pantothenate kinase-associated neurodegeneration. Because the clinical manifestations are diverse and complicated, in this review we present features of inheritance, age of onset, neuroimaging and laboratory findings, as well as the spectrum of central and peripheral neurological abnormalities and extraneuronal involvement to help distinguish the four specific syndromes.     

轻型缺血性卒中静脉溶栓后双重抗血小板疗效观察

目的 观察rt-PA静脉溶栓联合双重抗血小板治疗轻型缺血性卒中的有效性及安全性。 方法 以2013年12月-2016年12月在石家庄市第一医院连续住院治疗的轻型缺血性卒中患者为研究 对象,将其随机分为对照组、溶栓+单抗组和溶栓+双抗组。对照组不进行静脉溶栓,长期口服阿 司匹林（100 mg/d）抗血小板治疗;溶栓+单抗组在rt-PA静脉溶栓（0.9 mg/kg,最大剂量90 mg）基 础上长期单用阿司匹林（100 mg/d）抗血小板治疗;溶栓+双抗组在溶栓后单抗基础上加用氯吡格雷 （75 mg/d）双重抗血小板治疗,双抗治疗21 d后改为阿司匹林长期单抗治疗。随访3个月,有效性指标 为3个月时NIHSS 0～1分、Barthel指数（Barthel index,BI）95～100分和mRS 0～1分的比例,3个月时缺 血性卒中的复发率;安全性指标为治疗24 h出血转化和症状性出血转化的发生率。另外比较三组间 基线和3个月时血清hs-CRP和IL-6的水平差异。 结果 研究共纳入85例患者,对照组28例,溶栓+单抗组28例,溶栓+双抗组29例,全部患者均完 成3个月随访,无死亡患者。对照组、溶栓+单抗组和溶栓+双抗组3个月随访时NIHSS 0～1分比例分 别为46.43%、78.57%和93.10%,BI 95～100分比例分别为53.57%、82.14%和89.66%,mRS 0～1分 的比例分别为50.00%、82.14%和93.10%,三组上述有效性指标差异均有统计学意义,两两比较显 示,溶栓+双抗组高于溶栓+单抗组和对照组,溶栓+单抗组高于对照组,差异均有统计学意义;对 照组、溶栓+单抗组和溶栓+双抗组3个月时缺血性卒中复发率分别为32.14%、7.14%和3.45%,差异 有统计学意义。安全性指标方面,三组均无出血转化事件。对照组、溶栓+单抗组和溶栓+双抗组3 个月时的hs-CRP水平分别为11.92±3.58 mg/L、9.04±2.85 mg/L和6.04±2.65 mg/L,IL-6水平分别为 26.18±4.65 ng/L、16.11±6.93 ng/L和12.84±2.57 ng/L,三组上述炎症因子水平差异均有统计学意 义,其中溶栓+双抗组低于溶栓+单抗组和对照组,溶栓+单抗组低于对照组。 结论 对于急性轻型缺血性卒中患者,rt-PA静脉溶栓治疗后短期双重抗血小板治疗可显著改善患 者神经功能,降低炎症因子水平,降低复发率,且不增加出血风险。     

Gene-environment interaction and covariation in schizophrenia: the role of obstetric complications

While genetic factors account for a significant proportion of liability to schizophrenia, a body of evidence attests to a significant environmental contribution. Understanding the mechanisms through which genetic and environmental factors coalesce in influencing schizophrenia is critical for elucidating the pathways underlying psychotic illness and for developing primary prevention strategies. Although obstetric complications (OCs) remain among the most well-documented environmental indicators of risk for schizophrenia, the pathogenic role they play in the etiology of schizophrenia continues to remain poorly understood. A question of major importance is do these factors result from a genetic diathesis to schizophrenia (as in gene-environment covariation), act additively or interactively with predisposing genes for the disorder in influencing disease risk, or independently cause disease onset? In this review, we evaluate 3 classes of OCs commonly related to schizophrenia including hypoxia-associated OCs, maternal infection during pregnancy, and maternal stress during pregnancy. In addition, we discuss several mechanisms by which OCs impact on genetically susceptible brain regions, increasing constitutional vulnerability to neuromaturational events and stressors later in life (ie, adolescence), which may in turn contribute to triggering psychosis.