简介:BACKGROUND:Increasingevidencesuggestsoverlappedgeneticsusceptibilityacrosstraditionalclassificationsystemsthatdividedpsychoticdisordersintoschizophreniaoraffectivedisorder.OBJECTIVE:ThisstudyaimedtoexplorewhetherschizophreniaandaffectivedisordersharegeneticsusceptibilityinNOTCH4andGRIK2lociinapopulationofHanChinese.DESIGN:Repetitivemeasurements.SETTING:TheexperimentwascarriedoutatShanghaiMentalHealthCenterandHongkouMentalHealthCenterofShanghaibetweenJanuary2001andJune2004.PARTICIPANTS:Sixty-fivemixedpedigrees(sufferingfromvariousdiseases,incombinationwithschizophreniaandaffectivedisorder),composedof45completedtriosand20single-parentfamilies,wereselectedfromShanghaiMentalHealthCenterandHongkouMentalHealthCenterofShanghaibetweenJanuary2001andJune2004.ProbandsreceivedclinicaldiagnosisaccordingtoICD-10;anindependentclinicianusedidenticalcriteriatoreviewalldiagnoses.AllsubjectswereHanChineseinoriginandprovidedinformedconsent.Therewere65probandsand110parentsamongthesubjects.Theprobandscomprised30malesand35females:33withschizophrenia,32withaffectivedisorder,meanageof(30.9±9.8)years,meanageofonset(24.3±8.8)years,meanduration(6.6±7.0)years,andmeanageofparents(58.8±10.9)years.METHODS:DNAsamplesfromprobandsandtheirbiologicalparentswereextractedfromperipheralbloodaccordingtostandardmethods.Fourpolymorphisms,-1725T/Gand-25T/CinNOTCH4,rs6922753T/Candrs2227283G/AinGRIK2,wereamplifiedandgenotypedwithPCR-RFLPtechniques.MAINOUTCOMEMEASURES:AssociationbetweenNOTCH4,GRIK2polymorphism,andschizophreniawasanalyzedbytransmissiondisequilibriumtest(TDT).RESULTS:Sixty-fiveprobandsand110parentswereincludedintheresultanalysis,withnodropouts.Theresultsshowedthatthe-25T/CpolymorphismofNOTCH4associatedsignificantlywithaffectivedisorderand-1725G/-25Thaplotypewit
简介:目的研究富含亮氨酸重复序列免疫球蛋白样蛋白1(LRIG1)、表皮生长因子受体(EGFR)、ECadherin及N-Cadherin在不同病理级别胶质瘤中表达差异,探讨LRIG1在胶质瘤恶性进展中可能的作用机制。方法收集74例胶质瘤患者手术标本,包含12对原发及复发配对胶质瘤标本,采用qRT-PCR检测LRIG1、EGFR、E-Cadherin、N-Cadherin基因的表达,并采用免疫印迹检测LRIG1、EGFR、E-Cadherin、NCadherin、Vimentin蛋白表达情况。结果随着胶质瘤病理级别的升高,LRIG1、E-Cadherin基因及蛋白表达水平降低,EGFR、N-Cadherin基因及蛋白表达水平升高,差异均具有统计学意义(均P〈0.05)。WHOⅢ-Ⅳ组胶质瘤EGFR/LRIG1及N-Cadherin/E-Cadherin比值显著高于WHOⅠ-Ⅱ组(均P〈0.05)。EGFR/LRIG1与NCadherin/E-Cadherin变化之间存在正相关(r=0.56,P〈0.05)。对原发及复发配对胶质瘤标本的研究结果与上述一致。结论胶质瘤中EGFR/LRIG1表达失衡,可能通过诱导上皮间质转化(EMT)促进胶质瘤细胞的恶性进展。LRIG1可能成为胶质瘤治疗的新靶点。
简介:SpinaldorsalhornN-Methyl-D-asparticacidreceptor2B(NR2B)overexpressionplaysanimportantroleintheproductionandmaintenanceofneuropathicpain.BecausesmallinterferingRNA(siRNA)caninhibitNR2Bexpression,siRNAmayprovideanovelapproachtotreatneuropathicpainandpossiblynerveinjury.However,anefficientandsafevectorforNR2BsiRNAhasnotbeendiscov-ered.Thisstudyshowsthatawatersolublelipopolymer(WSLP)comprisedoflowmolecularweightpolyethyleneimine(PEI)andcholesterolcandeliversiRNAtargetingNR2Bforthetreatmentofneuropathicpain.ResultsshowthatintrathecalinjectionofWSLP/siRNAcomplexesfor3daysin-hibitNR2BgeneexpressionwithreductionsinmRNAandproteinlevelsby59%and54%,respec-tively,comparedwithcontrolrats(P<0.01).InjectionofWSLPcomplexedwithscrambledsiRNA,orPEIwithsiRNAdidnotshowthisinhibitoryeffect.Moreover,injectionofWSLP/siRNAcomplexessignificantlyrelievedneuropathicpainat3,7,12,and21days,whileinjectionofWSLPwithscrambledsiRNAorPEIwithsiRNAdidnot.TheseresultsdemonstratethatWSLPcanefficientlydeliversiRNAtargetingNR2Binvivoandrelieveneuropathicpain.
简介:目的观察急性脑梗死患者Toll样受体4(TLR4)mRNA表达及与TNF-α仅浓度的相关性,初步探讨TLR4在急性脑梗死缺血炎性损伤中的作用,为临床治疗脑梗死提供新的思路。方法分别运用RT-PCR法、ELISA法测定35例急性脑梗死患者的外周血单个核细胞(淋巴细胞、单核细胞)TLR4mRNA表达及血清TNF-α仅浓度,同期与20例正常者、20例动脉粥样硬化患者比较。结果脑梗死组发病第1天TLR4mRNA表达、血清TNF-α仅浓度均显著高于正常对照组和动脉粥样硬化组(P〈0.01)。TLR4mRNA表达与血清炎性因子TNF-α仅浓度呈正相关(P〈0.01)。结论脑梗死患者急性期外周血单个核细胞TLR4mRNA表达上调,可能通过促使炎性因子产生分泌增多来介导脑缺血炎性损伤。
简介:目的研究生长抑制因子4(ING4)在脑胶质瘤中的表达和姜黄素(curcumin)对脑胶质瘤的治疗作用,揭示curcumin抗脑胶质瘤作用的分子机制。方法体外培养U251胶质瘤细胞并以不同浓度curcumin处理细胞;以药物敏感试验和流式细胞仪分别检测curcumin对胶质瘤细胞生长和细胞周期的影响,以DNA梯度凝胶电泳检测细胞凋亡,以Westernblot分析curcumin处理后蛋白表达变化。结果ING4蛋白在正常神经细胞中高表达,在U251细胞中几乎不表达。低剂量curcumin对U251细胞无明显抑制作用,而高剂量curcumin对U251细胞存在明显的生长抑制作用,生长抑制率达35%。10μMcurcumin作用24h后,U251细胞中ING4蛋白表达水平显著增加。结论高剂量curcumin通过诱导ING4表达上调,抑制脑胶质瘤细胞体外生长。
简介:Thegenesfor5-lipoxygenaseactivatingprotein(ALOX5AP)andphosphodiesterase4D(PDE4D)havebeendemonstratedassusceptibilitygenesforlacunarintheIcelandicandPakistanipopulations,butlittleisknownabouttheroleofthesegenesinChinesepopulations.Thepresentstudyutilizedpolymerasechainreactionandligasedetectionreactiontodetectsinglenucleotidepolymorphisms(SNPs)in280consecutivestrokepatientsand258unrelatedpopulation-basedcontrolsfromNanjing,JiangsuProvince,China.Theallelefrequency,genotypes,andhaplotypesofthetwoSNPs(rs456009andrs966221)inPDE4Dweresimilarbetweenthetwogroups.However,Aallelefrequencyofrs4073259(A/G)andrs4769055(A/C)intheALOX5APgeneexhibiteddifferencesintwogroups,andespeciallythehaplotypeoftheSNPwassignificantlydifferentbetweenthetwogroups.ResultssuggestedthattheALOX5APgenemightbeinvolvedinlacunarinfarct,whilePDE4DgenewasnotariskfactorforlacunarinfarctinindividualsfromJiangsuProvince,China.
简介:BACKGROUND:Previousexperimentshaveconfirmedbonemorphogeneticproteins(BMPs)upregulatecholinergicexpressioninneuronsisolatedfromtheembryonicrathippocampusandcerebralcortex.Therefore,BMPscouldbeusefulfortreatingAlzheimer'sdiseaseandotherneurodegenerativediseases.OBJECTIVE:BMP-4wasinfusedintothehippocampaldentategyrusoffornix-fimbriatransectedratstotesttheeffectsofBMP-4oncholinergicexpressionindentategyrusneurons,andtoobservechangesinspatialmemorybehavior.DESIGN:Arandomizedcontrolledanimalexperiment.SETTING:DepartmentofNeurosurgeryandLaboratoryforCellBiology,InstituteofGeriatrics,GeneralHospitalofChinesePLA.MATERIALS:Twenty-sevenhealthyadultmaleSpragueDawley(SD)rats,weighing250-300g,wereprovidedbytheLaboratoryAnimalCenteroftheGeneralHospitalofChinesePLA.Reagents:BMP-4(B-2680,SigmaCompany)andcholineacetyltransferase(ChAT)antibody(AB5042,ChemiconCompany)wereusedinthisstudy.Equipments:aratstereotaxicinstrument(type:SN-2N,NarushigeGroup,Japan)andImage-prog-plusimageanalysissoftware(MediaCyberneticscompany,USA)wereusedinthisstudy.Theprotocolwascarriedoutinaccordancewithethicalguidelinesfortheuseandcareofanimals.METHODS:ThisexperimentwasperformedintheInstituteofGeriatrics,GeneralHospitalofChinesePLAbetweenJuly2004andMarch2005.Ratswererandomlydividedinto4groups:Alzheimer'sdiseasegroup(n=7),normalcontrolgroup(n=5),BMP-4-Alzheimer'sdiseasegroup(n=8),andmodelgroup(n=7).IntheAlzheimer'sdiseasegroup,thelefthippocampalfornix-fimbriaofratswastransectedtomimicAlzheimer'sdiseasesymptoms.IntheBMP-4-Alzheimer'sdiseasegroup,1μLBMP-4(10mg/L)wasperfusedintotheleftdentategyruswithamicroinjectorat1μL/min.Inthemodelgroup,1μLsalinewasperfusedintothesamepositionbythesamemethod.Twenty-eightdaysafterinjection,Morriswatermazetestwasperformedinallr
简介:目的探讨成人脑室-腹腔分流术后晚期感染并发症的临床特点及治疗措施。方法回顾性分析北京协和医院神经外科收治的4例脑积水术后感染患者的临床资料。对术后出现腹腔源性感染及多发感染并发症进行分析,并复习相关文献,总结其临床特点。结果4例术后晚期感染者均为交通性脑积水行脑室-腹腔分流术后患者。其中2例患者表现为粘连性肠梗阻、1例患者为多发腹腔内脓肿,1例患者为肺部及泌尿系感染,均合并颅内感染。经拔除脑室-腹腔分流管、抗生素治疗后感染均得到控制,后期行二次分流手术,疗效满意出院。随访6个月以上,4例患者均无感染复发。结论脑室-腹腔分流术后晚期感染,尤其腹腔源性感染临床相对少见,并常合并颅内感染。其治疗过程复杂,持续引流及系统性抗生素治疗是关键。
简介:目的研究β--七叶皂甙钠对大鼠脑出血后水通道蛋白4(AQP4)表达及脑水肿的影响,探讨β--七叶皂甙钠治疗出血性脑水肿的作用机制。方法在大鼠苍白球注射胶原酶制作脑出血模型,采用干湿重法观察脑水肿的变化;应用免疫组织化学方法检测脑组织AQP4表达。结果脑出血模型大鼠病灶侧脑含水量、血肿周围AQP4的表达水平均明显高于假手术组(均P〈0.01);各个时间点β--七叶皂甙钠治疗组病灶侧脑含水量以及血肿周围AQP4的表达水平均明显低于对照组(均P〈0.05);AQP4表达水平与脑含水量呈正相关(r=0.976,P〈0.01)。结论β--七叶皂甙钠能明显减轻脑出血后脑水肿及AQP4的表达,β--七叶皂甙钠可能抑制AQP4的表达而减轻脑水肿。
简介:目的探讨GATA-3及Th2细胞因子IL-4与多发性肌炎(PM)/皮肌炎(DM)的关系。方法用RT-PCR方法检测PM/DM患者外周血单个核细胞(PBMC)中GATA-3、IL-4的mRAN表达,并与正常健康人进行比较。结果PM、DM组中GATA-3mRNA表达阳性率(85.7%,86.4%)均高于正常对照组(25%)(P〈0.05);PM、DM组GATA-3的表达强度(0.268,0.411)均高于正常对照组(0.000)(P〈0.05);皮肌炎IL-4mRNA的表达强度(0.251)高于正常对照组(0.000)(P〈0.05);GATA-3与IL-4的表达强度呈正相关(r=0.475,P〈0.05)。结论皮肌炎的Th2细胞过度分化及体液免疫增强可能与GATA-3表达增强有关。