简介：ＴＨＥＣＥＲＶＩＸＭＵＬＴＩ－ＶＩＲＵＳＥＳＩＮＦＥＣＴＩＯＮＡＮＤＴＨＥＤＥＶＥＬＯＰＭＥＮＴＯＦＣＥＲＶＩＣＡＬＣＡＲＣＩＮＯＭＡＳＺｈａｎｇＷｅｉ张伟；ＪｉｎＳｎｕｎｑｉａｎ金顺钱；ＬｉｕＢｏｑｉ刘伯齐；ＬｉａｎｓＸｉａｏ梁肖；ＭｉｎｇＬｉｈｕ...

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简介：Objective:Multiplemechanismsunderlyingthedevelopmentofportalveintumorthrombus(PVTT)inhepatocellularcarcinoma(HCC)havebeenreportedrecently.However,theoriginsofPVTTremainunknown.Increasingmulti-omicsdataonPVTTsinHCCshavemadeitpossibletoinvestigatewhetherPVTTsoriginatefromthecorrespondingprimarytumors(Ts).Methods:TheclonalrelationshipbetweenPVTTsandtheircorrespondingprimaryTswasinvestigatedusingdatasetsdepositedinpublicdatabases.OneDNAcopynumbervariationsdatasetandthreegeneexpressiondatasetsweredownloadedfortheanalyses.ClonalityanalysiswasperformedtoinvestigatetheclonalrelationshipbetweenPVTTsandTsfromanindividualpatient.DifferentialgeneexpressionanalysiswasappliedtoinvestigatethegeneexpressionprofilesofPVTTsandTs.Results:Oneoutof19PVTTshadnoclonalrelationshipwithitscorrespondingT,whereastheothersdid.ThePVTTswithindependentclonaloriginshoweddifferentgeneexpressionandenrichmentinbiologicalprocessesfromtheprimaryTs.Basedontheuniquegeneexpressionprofiles,agenesignatureincluding24geneswasusedtoidentifypairsofPVTTsandprimaryTswithoutanyclonalrelationship.ValidationinthreedatasetsshowedthatthesetypesofpairsofPVTTsandTscanbeidentifiedbythe24-genesignature.Conclusions:OurfindingsshowadirectevidenceforPVTToriginandconsolidatetheheterogeneityofPVTTsobservedinclinic.TheresultssuggestthatPVTTinvestigationatamolecularlevelisclinicallynecessaryfordiagnosisandtreatment.

简介：Objective:ToevaluatethefeasibilityofDNAimagecytometry(DNA-ICM)asaprimaryscreeningmethodforesophagealsquamouscellcancer(ESCC).Methods:Atotalof5,382localresidentsaged40–69yearsfromthreehigh-riskareasinChina(LinzhouinHenanprovince,FeichenginShandongprovinceandCixianinHebeiprovince)from2008to2011wererecruitedinthispopulation-basedscreeningstudy.And2,526subjectsdeclinedtoreceiveendoscopicbiopsyexaminationwithLugol'siodinestaining,while9and815subjectswereexcludedfromliquid-basedcytologyandDNA-ICMtestrespectivelyduetoslidequality.Finally,2,856,5,373and4,567subjectswereenrolledintheanalysisforendoscopicbiopsyexamination,liquid-basedcytologyandDNA-ICMtest,respectively.Sensitivity(SE),specificity(SP),negativepredictivevalues(NPV)andpositivepredictivevalues(PPV)aswellastheir95%confidenceintervals(95%CI)forDNA-ICM,liquid-basedcytologyandthecombinationofthetwomethodswerecalculated.Receiveroperatingcharacteristic(ROC)curveswereappliedtodeterminethecutoffpointofDNA-ICMforesophagealcancer.Results:DNA-ICMresultsweresignificantlycorrelativewithesophagealcancerandprecancerlesions(χ~2=18.016,P<0.001).Thecutoffpointswere5,802,5,803and8,002basedondissimilarpathologicaltypesoflowgradeintraepithelialneoplasia(LGIN),highgradeintraepithelialneoplasia(HGIN),andESCC,respectively,and5,803waschoseninthisstudyconsideringtheSEandSP.TheSE,SP,PPV,NPVofDNA-ICMtest(cutoffpoint5,803)combinedwithliquid-basedcytology[thresholdatypicalsquamouscellsofundeterminedsignificance(ASCUS)]wereseparately72.1%(95%CI:70.3%-73.9%),43.3%(95%CI:41.3%-45.3%),22.8%(95%CI:21.1%-24.5%)and87.0%(95%CI:85.7%-88.3%)forLGIN,85.7%(95%CI:84.3%-87.1%),41.3%(95%CI:39.3%-43.3%),4.6%(95%CI:3.8%-5.4%)and98.9%(95%CI:98.5%-99.3%)forHGIN,and96.0%(95%CI:95.2%-96.8%),40.8%(95%CI:38.8%-42.8%),1.7%(95%CI:1.2%-2.2%)and99.9%

简介：Objective:Toinvestigatetheinvitrocleavageabilityandeffectsonapoptosisandcellgrowthofthebcr-ablfusiongenespecificmulti-unitribozymes.Methods:Threefusionpointspecificribozymesweredesignedandthemulti-unitribozymes'invitrotranscriptionvectorandretroviralvectorwereconstructed.Theinvitrocleavageabilitywastested.TheretroviralvectorwastransfectedintoK562cellandtheeffectsonproliferation,apoptosis,cellcycleandcellstructurewereobserved.Results:Multi-unitribozymeshadinvitrocleavageefficiencyof70.8%,whichwasmoreefficientthansingle-unitanddouble-unitribozymes.TransfectionoftheretroviralvectoroftheribozymeintoK562cells,inducedinhibitionofcellgrowthandapoptosis.TheincorporationrateofDNAinribozymestransfectedK562cellswasgreatlydecreasedalongwithtimepassed,withaninhibitionrateofmorethan50%after96hoftransfection.UnderFCM,18.4%ofthecellsunderwentapoptosis72haftertransfectionandmorecellswereblockedinGphase,withtheratioinSphasegreatlydecreased(41.9%).Underelectronmicroscope,compactionofnuclearchromatinandapoptosisbodieswereobserved.Conclusion:Multi-unitribozymesspecifictobcr-ablfusiongenecanbeusedtotreatCMLandtopurgebonemarrowforself-grafting.