简介：AIMTotestwhetherNox1playsaroleintyphlitisinducedbySalmonellaentericaserovarTyphimurium(S.Tm)inamousemodel.METHODSEight-week-oldmalewild-type(WT)andNox1knockout(KO)C57BL6/J(B6)micewereadministeredmetronidazolewaterfor4dtomakethemsusceptibletoS.Tminfectionbytheoralroute.Themiceweregivenplainwaterandadministeredwith4differentdosesofS.Tmbyoralgavage.Themicewerefollowedforanother4d.Fromthetimeofthemetronidazoleapplication,themicewereobservedtwicedailyandweigheddaily.Theileum,cecumandcolonwereremovedforsamplingatthefourthdaypost-inoculation.PortionsofallthreetissueswerefixedforhistologyandplacedinRNAlaterformRNA/cDNApreparationandquantitativereal-timePCR.ThecontentsofthececumwererecoveredforestimationofS.TmCFU.RESULTSWefoundNox1-knockout(Nox1-KO)micewerenotmoresensitivetoS.TmcolonizationandinfectionthanWTB6mice.Thisconclusionisbasedonthefollowingobservations:(1)S.Tm-infectioninducedsimilarweightlossinNox1-KOmicecomparedtoWTmice;(2)thesameS.TmCFUwasrecoveredfromthececalcontentofNox1-KOandWTmiceregardlessoftheinoculationdose,exceptthelowestinoculationdose(2×106CFU)forwhichtheNox1-KOhadone-loglowerCFUthanWTmice;(3)thereisnodifferenceincecalpathologybetweenWTandNox1-KOgroups;and(4)therearenoS.Tminfection-inducedchangesingeneexpressionlevels(IL-1b,TNF-α,andDuox2)betweenWTandNox1-KOgroups.TheAlpigeneexpressionwasmoresuppressedbyS.TmtreatmentinWTthantheNox1-KOcecum.CONCLUSIONNox1doesnotprotectmicefromS.Tmcolonization.Nox1-KOprovidesaveryminorprotectiveeffectagainstS.Tminfection.UsingNOX1-specificinhibitorsforcolitistherapyshouldnotincreaserisksinbacterialinfection.

简介：背景:协同刺激分子的异常表达与肿瘤细胞免疫逃逸关系密切。程序性死亡受体-1(PD-1)是重要的负性协同刺激分子,与相关配体结合后可诱导并维持肿瘤细胞的免疫耐受,从而促进肿瘤的发生、发展。目的:探讨结直肠癌患者外周血PD-1的表达及其临床意义。方法:选取2015年3月—2015年9月苏州大学附属第一医院的88例结直肠癌患者,以16名健康志愿者作为对照。采用ELISA法检测血清可溶性PD-1(sPD-1)含量,流式细胞术检测外周血CD3+T细胞上PD-1的表达。结果:结直肠癌患者外周血sPD-1含量和CD3+T细胞上PD-1阳性表达率均显著高于对照组(P<0.05),且sPD-1含量与肿瘤分化程度、淋巴结转移和Dukes分期相关(P<0.05),而与患者的性别、年龄和肿瘤部位无关(P>0.05)。结论:结直肠癌患者外周血PD-1高表达,且与肿瘤分期、转移呈正相关。检测PD-1有助于估计病情的进展,有望成为新的肿瘤标记物或抗肿瘤靶点。

简介：一、临床资料患者,男,76岁,山东威海农民。因胸骨后梗噎感伴呕吐8d于2015年4月24日入院。患者于入院前8d食用生海螺肉时,因牙齿不全未经咀嚼整体吞入食管,随后出现胸骨后梗噎感,自觉食物堵塞不能下行,少量饮食水后即出现呕吐,呕吐物为吞咽的食水,呕吐后梗噎感无缓解;无呕血黑便,无胸痛、发热、呼吸困难等不适。

简介：背景:Gankyrin是一个含锚蛋白重复序列的原癌蛋白,其高表达参与了多种恶性肿瘤的发生、发展进程。目的:探讨下调gankyrin表达对胃癌细胞增殖能力的影响及其可能机制。方法:以携带gankyrinsiRNA的慢病毒载体转染人胃癌细胞株MKN28,分别采用MTT实验、流式细胞术和蛋白质印迹法检测下调gankyrin表达对MKN28细胞增殖、细胞周期分布及其β-catenin/cyclinD1信号通路的影响。结果:慢病毒载体的转染效率在90%以上,转染gankyrinsiRNA后,MKN28细胞gankyrin蛋白表达显著受抑(P<0.01)。与未转染慢病毒和转染对照病毒的细胞相比,转染gankyrinsiRNA的MKN28细胞体外生长于第3天起显著受抑,细胞周期G1期细胞比率增高,S期细胞比率降低,细胞中的β-catenin和cyclinD1表达水平降低,差异均有统计学意义(P<0.01)。结论:下调胃癌细胞中的gankyrin表达可通过抑制β-catenin/cyclinD1信号通路引起细胞周期G1期阻滞和细胞增殖抑制,gankyrin有望成为胃癌靶向治疗的新靶点。

简介：我们诊治1例原发性肝癌合并下腔静脉和右心房瘤栓致肺栓塞患者，现报道如下。1病例摘要患者男性，54岁，农民。既往体健。因“活动后胸闷、气促5天”于2014年3月1日入院。查体：体温：36．9℃，脉搏：106次份，呼吸25次／分，血压90／50mmHg。

简介：AIM:Toelucidatethemechanism(s)bywhichS-adenosyl-L-methionine(SAM)decreaseshepatitisCvirus(HCV)expression.METHODS:WeexaminedtheeffectsofSAMonviralexpressionusinganHCVsubgenomicrepliconcellculturesystem.Huh7HCV-repliconcellsweretreatedwith1mmol/LSAMfordifferenttimes(24-72h),thentotalRNAandproteinswereisolated.cDNAwassynthesizedandrealtime-PCRwasachievedtoquantifyHCV-RNA,superoxidedismutase1and2(SOD-1,SOD-2)catalase,thioredoxin1,methionineadenosyltransferase1Aand2A(MAT1A,MAT2A)expression,andGAPDHandRPS18asendogenousgenes.Expressionofcellularandviralproteinwasevaluatedbywestern-blotanalysisusingantibodiesvsHCV-NS5A,SOD-1,SOD-2,catalase,thioredoxin-1,MAT1A,MAT2A,GAPDHandactin.TotalglutathionelevelsweremeasuredatdifferenttimesbyEllman’srecyclingmethod(0-24h).Reactiveoxidativespecies(ROS)levelswerequantifiedbythedichlorofluoresceinassay(0-48h);Pyrrolidindithiocarbamate(PDTC)wastestedasanantioxidantcontrolandH2O2asapositiveoxidantagent.RESULTS:SAMexpositiondecreasedHCV-RNAlevels50%-70%comparedtonon-treatedcontrols(24-72h).SAMinducedasynergicantiviraleffectwithstandardIFNtreatmentbutitwasindependentofIFNsignaling.Inaddition,1mmol/LSAMexpositiondidnotmodifyviralRNAstability,butitneedscellulartranslationmachineryinordertodecreaseHCVexpression.TotalglutathionelevelsincreaseduponSAMtreatmentinHCV-repliconcells.Transcriptionalantioxidantenzymeexpression(SOD-1,SOD-2andthioredoxin-1)wasincreasedatdifferenttimesbutinterestingly,therewasnosignificantchangeinROSlevelsuponSAMtreatment,contrarytowhatwasdetectedwithPDTCtreatment,whereanaverage40%reductionwasobservedinexposedcells.TherewasaturnoverfromMAT1A/MAT2A,sinceMAT1Aexpressionwasincreased(2.5fold-timesat48h)andMAT2Awasdiminished(from24h)uponSAMtreatmentatboththetranscriptionalandtranslationall

简介：AIMToinvestigatetheroleofthecomplement5a(C5a)/C5areceptor(C5aR)pathwayinthepathogenesisofacuteliverfailure(ALF)inamousemodel.METHODSBALB/cmicewererandomlyassignedtodifferentgroups,andintraperitonealinjectionsoflipopolysaccharide(LPS)/D-galactosamine(D-GalN)(600mg/kgand10μg/kg)wereusedtoinduceALF.TheKaplanMeiermethodwasusedforsurvivalanalysis.Serumalanineaminotransferase(ALT)levels,atdifferenttimepointswithina1-wkperiod,weredetectedwithabiochemistryanalyzer.Pathologicalexaminationoflivertissuewasperformed36hafterALFinduction.Serumcomplement5(C5),C5a,tumornecrosisfactor-α(TNF-α),interleukin(IL)-1β,IL-6,high-mobilitygroupproteinB1(HMGB1)andsphingosine-1-phosphatelevelsweredetectedbyenzyme-linkedimmunosorbantassay.Hepaticmorphologicalchangesat36hafterALFinductionwereassessedbyhematoxylinandeosinstaining.ExpressionofC5aR,sphingosinekinase1(SphK1),p38-MAPKandp-p38-MAPKinlivertissue,peripheralbloodmononuclearcells(PBMCs)andperitonealexudativemacrophages(PEMs)ofmiceorRAW264.7cellswasanalyzedbywesternblotting.C5aRmRNAlevelsweredetectedbyquantitativereal-timePCR.RESULTSActivationofC5andup-regulationofC5aRwereobservedinlivertissueandPBMCsofmicewithALF.BlockadeofC5aRwithaC5aRantagonist(C5aRaC5aRa)significantlyreducedthelevelsofserumALT,inflammatorycytokines(TNF-α,IL-1βandIL-6)andHMGB1,aswellasthelivertissuedamage,butincreasedthesurvivalrates(P<0.01forall).BlockadeofC5aRdecreasedSphK1expressioninbothlivertissueandPBMCssignificantlyat0.5hafterALFinduction.C5aRapretreatmentsignificantlydownregulatedthephosphorylationofp38-MAPKinlivertissuesofALFmiceandC5astimulatedPEMsorRAW264.7cells.Moreover,inhibitionofp38-MAPKactivitywithSB203580reducedSphK1proteinproductionsignificantlyinPEMsafterC5astimulation.CONCLUSIONTheC5a/C5aRpath