论文泛读课件

论文泛读1.Meta-analysis-胃肠病>10分(Gastroenterology,Gut,Hepatology,Journalofhepatology)在2014发表的meta分析(风险，预后，诊断…)2.KynurenineIncreasedIntakeofVegetables,ButNotFruit,ReducesRisk

forHepatocellularCarcinoma:AMeta-analysisMethods1Databases:PubMed(Medline),WebofScience,andEMBASE2Time:from1956toMay31,20143Terms:(fruitorvegetablesordietornutritionorlifestyle)combinedwith(hepatocellularcarcinomaorlivercancerorhepatomaorlivertumor)4SelectionCriteria:a.cohortorcase-control;b.exposurewasvegetables/fruit;c.outcomewasHCCincidence/mortality;d.oddsratiosorrelativerisks(RR)with95%(CIs).Animalstudies,reviews,letters,editorials,commentaries,abstracts,unpublishedstudies,andduplicatestudieswereexcluded.5DataExtracted:firstauthor’sname,publicationyear,location,design,numberofcases,numberofcontrols,dietaryassessment,HCCdiagnosismethod,comparisons,RRswithcorresponding95%CIsforthehighestcomparedwithlowestintake,andadjustedvariables.6QualityAssessment:Newcastle-Ottawascale.Amaximumof9points.Afinalscore>6wasregardedashighquality.StatisticalMethods1Software:STATAversion12.0.2

Model:Therandom-effectsmodel3

HeterogeneityAssessment:QandI2statistics,withI2>50%representingsubstantialheterogeneity.4Dose–responsemeta-analysis:GLST(Generalizedleastsquaresfortrendestimation)（atleast3quantitativecategories）5Subgroupanalysesstratifiedbypotentialconfoundingfactorsandmeta-regressionanalyseswerecarriedouttoexplorethesourcesofheterogeneity6Sensitivityanalysiswasperformedbyremovingonestudyeachtimeandexaminingtheinfluenceofaspecificstudyonthepooledresults.7PublicationbiaswasevaluatedusingafunnelplotandtheEgger’stest,withP<.1indicatingsignificantpublicationbias.“trimandfill”methodwasusedtocorrectpublicationbiasIncreasedIntakeofVegetables,ButNotFruit,ReducesRisk

forHepatocellularCarcinoma:AMeta-analysis营养学食物频率法问卷调查RelationshipofvitaminDstatuswithadvancedliverfibrosisandresponsetohepatitisCvirustherapy:Ameta-analysis.Methods1Databases:PubMed,SCOPUS,LILACS,CochraneLibraryliterature2Time:from1956toApril,20143Terms:(“hepatitisC”or“HCV”or“chronichepatitisC”)and(“vitaminD”or“ergocalciferol”or“cholecalciferol”).4SelectionCriteria:Included:a.patientswithHCVorHCV/HIV;b.ALFdatawerederivedfromhepaticbiopsy(notfromnoninvasivemarkers)inpatientsundergoingpegIFNa/ribavirintherapy;c.serumorplasma25(OH)Dlevels.Excluded:a.coinfectionwithHBV;b.absentinformationabout25(OH)Dlevels,studypopulation,HCVstatus,ornotenoughinformationtocalculateORand95%CI;c.samplesizelessthan40;d.receivedvitaminDsupplementation;e.reviews,letters,editorials,orclinicalcases.5QualityAssessment:modifiedNewcastle-Ottawascale.Score7ormorestarswereregardedashighquality.6Guideline:PRISMAALFaccordingtoMetavir(F3).DatacontainingadifferentscoreweretransformedtotheMetavirscore.2.SVRwasdefinedasanundetectableserumHCVRNAlevelupthrough24weeksaftertheendofHCVtreatment.HCV-GT1/4patientswereconsideredasdifficult-to-treatandHCV-GT2/3patientswereconsideredaseasy-to-treat.StatisticalMethods1Software:STATAversion11.0.2

Model:Afixedeffectmodelwasusedforhomogeneousstudies.Whensignificantheterogeneityexisted,arandomeffectmodelwasapplied.3

HeterogeneityAssessment:QandI2statistics,QstatisticP<0.1orI2>50%representingsubstantialheterogeneity.4Subgroupanalysesandmeta-regressionanalyses5Sensitivityanalysiswasperformedbyremovingonestudyeachtimeandexaminingtheinfluenceofaspecificstudyonthepooledresults.6PublicationbiaswasevaluatedusingafunnelplotandtheEgger’stest,withP<0.05indicatingsignificantpublicationbias.7GalbraithplotwasusedtodetectpossibleoutliersoftheheterogeneityPortalhypertensionontheoutcomeofsurgeryforhepatocellularcarcinomaincompensatedcirrhosis:asystematicreviewandmeta-analysis.Methods1Databases:Medline2Time:fromJanuary1996(yearofpublicationofthefirstarticleinthisareareportingthatHVPG≥10mmHgisanindependentnegativeprognosticfactoronpostoperativeoutcome)toOctober10,2013.3Terms:“hepatocellularcarcinoma”AND[“surgery”OR“hepatectomy”,OR“resection”]AND“portalhypertension”4SelectionCriteria:Included:a.originalpublicationsinEnglishwithfull-text;b.patientswithcirrhosisandHCCforsurgery;c.assessedportalhypertensionclearlystatinghowwasdefined;d.reportedpostoperativeoutcome(survivaland/orclinicaldecompensation).Clinicallysignificantportalhypertensionwasdefinedaccordingtothefollowingdefinitions:HVPG≥10mmHgorPVP≥20cmH2Oorstandardsurrogatecriteria:presenceofgastro-esophagealvaricesorplateletcount<100000/mlandspleendiameter>12cm.Excluded:casereports,reviews,correspondingletters,oreditorials.5QualityAssessment:QualityInPrognosisStudies(QUIPS).6Guideline:PRISMAStatisticalMethods1Software:

ReviewManager.2

Model:random-effectsmodel.3

HeterogeneityAssessment:X2andI2statistics,I2>50%representingsubstantialheterogeneity.4Subgroupanalysesandmeta-regressionanalyses5Sensitivityanalysis.6Publicationbias.7Agreementbetweenauthorsselectingthearticleswasassessedbycalculatingkappaconcordancecoefficient(k);agreementwasgradedbythescaleproposedbyLandisandKoch.Figure2.ImpactofCSPHonpostoperativeoutcomesofpatientswithHCCandcompensatedcirrhosisinalltheincludedstudies.PanelA:3-yearmortality;PanelB:5-yearmortality;PanelC:clinicaldecompensation.Figure3.Stratifiedmeta-analysisaccordingtothediagnosticmethodusedtoassessthepresenceofclinicallysignificantportalhypertension.PanelA:3-yearmortality;PanelB:5-yearmortality;PanelC:clinicaldecompensation.常见肝纤维化非侵袭性指标a:真阳性；b:假阳性；c:假阴性；d:真阴性。Sensitivity=

a/(a+c)

真阳性率，由金标准确诊有病的病例数（a+c)中试验组内所检测出阳性病例数(a)的比率Specificity=

d/(b+d)

真阴性率，由金标准确诊为无病的对照组（b+d)内所检测出阴性人数(d)的比率Positivelikelihoodratio(+LR)

=

SEN/1-SPE

筛检结果的真阳性率（a/a+c)与假阳性率即误诊率(b/b+d)之比。说明筛检试验正确判断阳性的可能性是错误判断阳性可能性的倍数。比值越大，试验结果阳性时为真阳性的概率越大。Negativelikelihoodratio

(-LR)

=

(1-SEN)/SPE筛检结果的假阴性率即漏诊率(c/a+c)与真阴性率(d/b+d)之比。表示错误判断阴性的可能性是正确判断阴性可能性的倍数。其比值越小，试验结果阴性时为真阴性的可能性越大。Thedatawereextractedand2×2tableswereconstructedtocalculatesensitivity,specificity,positivepredictivevalue(PPV)andnegativepredictivevalue(NPV)foreachreportedtestthreshold.肝穿刺活检APRIFIB-4ComparisonofDiagnosticAccuracyofAPRIandFIB-4for

DetectingLiverFibrosisinAdultPatientswithChronicHepatitisB

VirusInfection:ASystemicReviewandMeta-analysisMethods1Databases:Pubmed/Medline,EMBASE,CochraneLibrary,WebofKnowledge.2Time:01/2005-12/2013.3Terms:APRI,AST-to-plateletratioindex,AST,platelet,FIB-4,age,hepatitisBandnon-invasivemodelsandfibrosis.4SelectionCriteria:Included:a.evaluatedtheperformanceofAPRIorFIB-4fordetectingfibrosisinHBV-infectedpatients;b.liverbiopsywasusedasthereferencestandardforassessingfibrosis;c.Datacouldbeextractedtoallowtheconstructionofatleastone2×2tableoftestperformance;d.morethan30patients.Studiesincludinghumanimmunodeficiencyvirus(HIV)-co-infectedpatientswereexcluded.5QualityAssessment:TheQualityAssessmentofDiagnosticAccuracyStudies(QUADAS)score.Theoutcomesweretheidentificationofsignificantfibrosis,advancedfibrosisandcirrhosis,definedrespectivelyasMETAVIR,BattsandLudwigorScheuerstagesF2–F4,F3–F4andF4orasIshakstagesF3–F6,F4–F6andF5–F6.StatisticalMethods1Software:

Stata12.0,Meta-Discsoftware1.4,ReviewManager5.2andMedCalc12.7.0.2

Model:

a.TheZ-testwasusedtocomparetheAUCvaluesofAPRIandFIB-4forpredictingliverfibrosis.b.diagnosticoddsratios(DORs)usingaDer-SimonianandLairdrandomeffectsmodel.c.Summarysensitivitiesandspecificitieswerealsocalculatedemployingthebivariatemeta-analyticapproach.3

HeterogeneityAssessment:QandI2statistics,I2>50%representingsubstantialheterogeneity.4

Publicationbias.5Subgroupanalysis:Becausemeta-regressionanalysesarelimitedbythenumberofstudies,weexaminedmethodologicalheterogeneityonlyingroupsofmorethan10studies.ThreemeasureswereexaminetheaccuracyofAPRIandFIB-4forthediagnosisofsignificantfibrosis,advancedfibrosisandcirrhosis:theareaunderthesummaryreceiveroperatingcharacteristic(SROC),thesummarydiagnosticoddsratios(DORs)andthesummarysensitivitiesandspecificities.TheZ-testwasusedtocomparetheAUCvaluesofAPRIandFIB-4forpredictingliverfibrosis.Figure2.(A).SROCcurveofAPRIandFIB-4fordetectingsignificantfibrosis.(B).SROCcurveofAPRIandFIB-4fordetectingadvancedfibrosis.(C).SROCcurveoftheAPRIandFIB-4fordetectingcirrhosis.Figure3.(A1)DiagnosticaccuracyofAPRIforsignificantfibrosis;(A2)DiagnosticaccuracyofAPRIforadvancedfibrosis;and(A3)DiagnosticaccuracyofAPRIforcirrhosis.(B1)DiagnosticaccuracyofFIB-4forsignificantfibrosis;(B2)DiagnosticaccuracyofFIB-4foradvancedfibrosis;and(B3)DiagnosticaccuracyofFIB-4forcirrhosis.APRIFIB-4Figure4.Linearregressiontestoffunnelplotasymmetryforpublication.(A1)APRIdetectingsignificantfibrosis;(A2)APRIdetectingadvancedfibrosis;and(A3)APRIdetectingcirrhosis.(B1)FIB-4detectingsignificantfibrosis;(B2)FIB-4detectingadvancedfibrosis;and(B3)FIB-4detectingcirrhosis.Part2:Kynureninekynurenines—thatregulateimmunehomeostasisbyactingasAhRligandsandallowingthegenerationofregulatoryTcells,whichprotectmicefromchronichyperinflammatoryresponses.Increasedplasmakynureninelevelsandkynurenine-to-tryptophanratioshavebeenfoundinpatientswithsystemicinflammatoryresponsesyndrome,sepsisandsepticshock.Sublethaldose(10mgperkg)lungliverserumFigure2|AbsoluterequirementforAhR,functionalIDO1inLPStolerance.a,SurvivalofWTandLPS-primedWT(prWT),IDO1-deficient(prIdo1–/–)andIDO2-deficient(prIdo2–/–)miceafterrechallenge.n58–10;oneexperimentofthree.**P,0.001;log-ranktest.b,EndotoxinLD50intolerizedmice.n510.c,d,Histopathologyinlungsandliver,respectively;scalebar,100mm.Oneexperimentoftwo.e,Survivalofvariouslytreatedmice(n510;oneofthreeexperiments).**P,0.001(log-ranktest).f,Cytokinemeasurements(mean6s.d.ofthreeexperiments;n56).**P,0.001(two-tailedStudent’st-test).LPS10mg/kg-1w-40mg/kgAhR拮抗剂Figure3|LPStoleranceinducesAhR-andSrc-dependentIDO1phosphorylation.a,PhosphorylationofIDO1intotalsplenocytesisolatedfromLPS-tolerantmiceinoneexperimentofthree.pIDO1/IDO1ratiosshownbelowthegelsaremeanvaluesfromthethreeexperiments.*P,0.001(15minversussingleLPSexposure;two-tailedStudent’st-test).pIDO1,phosphorylatedIDO1.b,Splenicimmunofluorescentstaining.Scalebar,100mm.c,PhosphorylationofIDO1’sITIM2inWTandAhR-deficientcDCs.Oneexperimentofthree,ratiosbeingmeansfromthethreeexperiments.*P,0.001(30minversussingleLPSexposure;two-tailedStudent’st-test).isolatedspleencellsα-半乳糖基神经酰胺FIGURE1.UpregulationofIDOexpressionandactivityintheliveraftera-GalCerinjection.A,L-KynconcentrationsinserumdeterminedbyperformingtheHPLCmethodonWTandIDO-KOmicetreatedwitha-GalCer.Eachvalueisrepresentedbythemean(SEM)ofthreemice.pp,0.05.B,TherelativeexpressionlevelsofIDOmRNAintheliversofWTmiceadministereda-GalCerweremeasuredusingquantitativereal-timePCR.Theresultswerenormalizedbytheexpressionof18SmRNA.Eachvalueisrepresentedbythemean(SEM)ofthreemice.pp,0.05.C,ExpressionofIDOproteinintheliversofWTmice1daftertreatmentwitha-GalCerwasexaminedbyWesternblotanalysisandwasdeterminedusingtheGAPDHprotein.Dataarerepresentativeofatleastthreeindependentexperimentswithsimilarresults.D,ImmunohistochemicalanalysisofIDOintheliverofWTandIDO-KOmiceaftera-GalCerinjection.IDOproteinwasstainedbyusingalabeledstreptavidin-biotinkitcontainingbiotinylatedAbandperoxidase-labeledstreptavidin.Theperoxidasebindingsitesweredetectedbystainingwith3,39-diaminobenzidine.Scalebar,25mm.Originalmagnification3200.Dataarerepresentativeofatleastthreeindependentexperimentswithsimilarresults.FIGURE2.Inductionofliverinjurybya-GalCerinWTmiceandIDO-KOmice.A,SerumALTactivitywasmeasuredatvaryingtimepointsaftera-GalCerinjectionintoWTandIDO-KOmice.Eachvalueisrepresentedbythemean(SEM)ofthreemice.pp,0.05.B,HistopathologicalcharacteristicsofWTandIDO-KOmiceliversobservedat0,1,and2daftera-GalCeradministrationinthesemice.H&E,originalmagnification3200;scalebar,100mm.Arrowsdesignatenecroinflammatoryfociintheliver.Theseexperimentswererepeatedthreetimes,andthesameresultswereobtained.FIGURE3.a-GalCer–inducedTNF-aproductioninWTandIDO-KOmice.A,TNF-amRNAexpressionintheliversofWTandIDOKOmicethatwereadministereda-GalCer.ThemRNAlevelofTNF-awasnormalizedtothatof18SmRNA.Representativechartswerederivedfromtheanalysesofthreemicepergroup.B,SerumTNF-aconcentrationwasdeterminedbyELISAinWTandIDO-KOmiceaftera-GalCerinjection.Eachvalueisrepresentedbythemean(SEM)ofthreemice.pp,0.05.FIGURE4.a-GalCer–inducedcytokineandchemokineexpressioninWTmiceandIDO-KOmice.A,IL-2,IL-4,IL-6,andIFN-gmRNAexpressionintheliversofWTandIDO-KOmicethatwereadministereda-GalCer.B,mRNAexpressionofchemokines(MIP-2,MCP-1,andKC)intheliversofWTandIDO-KOmicethatwereadministereda-GalCer.C,TGF-bandIL-10mRNAexpressionintheliversofWTandIDO-KOmicethatwereadministereda-GalCer.ThemRNAlevelsofcytokinesandchemokineswerenormalizedtothoseof18SmRNA.D,SerumIL-6,MIP-2,andKCconcentrationsinWTandIDO-KOmiceaftera-GalCerinjectionweredeterminedbyELISA.Representativechartsderivedfromtheanalysesofthreemicepergroup.pp,0.05.FIGURE5.KineticsandlymphocytephenotypesofhepaticMNCsaftera-GalCerinjectionintoWTandIDO-KOmice.HepaticMNCsfromWT(blackbars)andIDO-KO(graybars)micewereobtainedat0,1,and2daftera-GalCerinjection.CellnumberswerequantifiedusingFACScananalysis.A,TotalnumberofhepaticMNCsaftera-GalCerinjection.B,NumberofCD32CD49b+cells,CD3+CD49b+cells,andCD3+CD49b2cellsaftera-GalCerinjection.C,NumberofCD4+andCD8+cellsaftera-GalCerinjection.D,NumberofCD11b+Gr-12cells,CD11b+Gr-1+cells,andCD11b2Gr-1+cellsat1daftera-GalCerinjection.ResultsarepresentedasthemeannumberofcellsofeachcelltypeofhepaticMNCsforatleastthreemicepergroup.ErrorbarsindicatetheSEM.pp,0.05.IHL,intrahepaticlymphocyte.FIGURE6.a-GalCer–inducedTNF-aproductioninCD49b+andCD11b+cells.FlowcytometricanalysisofintracellularTNF-aproducedbyhepaticCD49b+andCD11b+cellsobtainedfrommiceat0,5,and12haftera-GalCerinjectionandculturedfor4hinbrefeldinA.Dataarerepresentativeofatleastthreeindependentexperimentswithsimilarresults.FIGURE7.IDOinhibitor(1-MT)enhancesa-GalCer–inducedliverinjury.IDO-WTmicewereorallyadministered1-MTat0or5mg/mlindrinkingwaterfor3dbeforea-GalCerstimulation.SerumALTactivitywasanalyzedatvaryingtimepointsrelativetotheinjectionofa-GalCerinto1-MT–treatedandnontreatedmice.Representativechartswerederivedfromtheanalysesoffourorfivemicepergroup.Theseexperimentswereindependentlyperformedtwice(Exp.1andExp.2).ErrorbarsindicatetheSEM.pp,0.05.Fig.1.IncreasesinIDOexpressionandactivitywereobservedinHBV-Tg/IDO-WTmice

afterHBV-specificCTLinjection.(A)TherelativeexpressionlevelofIDOmRNAinliversofHBV-Tg/IDO-WTandHBV-Tg/IDO-KOmiceadministeredHBV-specificCTLwasmeasuredbyquantitativereal-timeRT-PCR.Theresultantdataarerepresentedasmeans±SDoftheresultsof4miceineachgroup.(B)ExpressionofIDOproteinintheliversofHBV-Tg/IDO-WTmiceat0d,1d,2d,and7dafterHBV-specificCTLinjectionwasexaminedbywesternblotanalysisandwasnormalizedtoβ-actinprotein.Dataarerepresentativeofatleast3independentexperimentswithsimilarresults.(C)IDOactivityintheliversofHBV-Tg/IDO-WTmiceat2dafterreceivingHBV-specificCTLinjections:Dataarerepresentedasmean±SDoftheresultsfrom4miceineachgroup.(D)KynurenineconcentrationsinplasmaweredeterminedusingHPLCforHBV-Tg/IDO-WTandHBV-Tg/IDO-KOmiceinjectedwithHBV-specificCTL.Dataarerepresentedasmean±SDoftheresultsfrom4miceineachgroup.*,pb0.05.Fig.2.HBV-specificCTL-inducedliverdiseaseinHBV-Tg/IDO-WTmiceandHBV-Tg/IDO-KOmice.(A)PlasmaALTlevelswereanalyzedatvaryingtimesrelativetotheinjectionof1×106HBV-specificCTLintoHBV-Tg/IDO-WT,HBV-Tg/IDO-KOandnon-HBV-Tgmice.Dataarerepresentedasmean±SDoftheresultsfrom4miceineachgroup.(B,C)HistopathologicalcharacteristicsofHBV-Tg/IDO-WTmiceandHBV-Tg/IDO-KOmice.HematoxylinandeosinstainingandTUNELstainingwereperformedinlivertissuesat2dafterinjectingthesemicewithCTL.Dataarerepresentedasmean±SDoftheresultsfrom5miceineachgroup.Scalebars,200μm(low-powerfield)and50μm(high-powerfield).*,p<0.05.Fig.3.CytokineandchemokineexpressioninthelivertissuesofHBV-Tg/IDO-WTandHBV-Tg/IDO-KOmiceafterHBV-specificCTLinjection.(A)TNF-α,IFN-γ,IL-6,IL-10,MCP-1andMIP-2mRNAexpressionwasdeterminedinliversfromHBV-Tg/IDO-WTandHBVTg/IDO-KOat0d,1d,2d,and7dafterCTLinjection.Dataarerepresentedasmean±SDoftheresultsfrom4to6miceineachgroup.(B)TNF-αandIFN-γmRNAexpressionwasdeterminedinparenchymalcellsandnon-parenchymalcellsofliversfromHBV-Tg/IDO-WTandHBVTg/IDO-KOat0dand2dafterCTLinjection.Dataarerepresentedasmean±SDoftheresultsfrom3miceineachgroup.*,p<0.05.Fig.4.Theeffectof1-MTandkynurenineonliverinjuryinducedbyHBV-specificCTLinHBV-Tgmice.(A,B)HBV-Tg/IDO-WTmicewereorallyadministered1-MTat0mg/mLor5mg/mLindrinkingwaterfor3dpriortoHBV-specificCTLinjection.PlasmaALTlevelswereanalyzedat0d,1d,2d,4d,and7dafterCTLinjection.Hematoxylinandeosinstainingwasperformedinmouselivertissuesat2dafterCTLinjection.(C,D)HBV-Tg/IDO-KOmicewereinjectedwithHBV-specificCTLfollowedbyintraperitonealinjectionwithkynurenine(KYN)daily.PlasmaALTlevelswereanalyzedat0d,1d,2d,4d,and7dafterCTLinjection(A,C).Hematoxylinandeosinstainingwasperformedinlivertissuesat2dafterCTLinjection(B,D).Dataarerepresentedasmean±SDoftheresultsfrom4to6miceineachgroup.*,p<0.05.Jul2014–

presentPostdoctoralfellowGeneralHospitalofShenyangMilitaryRegion·DepartmentofGastroenterologyChina·ShenyangSep2008–

Jun2014MedicalDoctorFourthMilitaryMedicalUniversity·XijingHospitalofDigestiveDiseasesChina·Xi’an"XijingHospitalofDigestiveDiseases,FourthMilitaryMedicalUniversity"isright.Pleasedon'tcorrect.Jul2006–

presentResidentNo.463HospitalofChinesePLA·DepartmentofGastroenterologyChina·Shenyang,LiaoningLetter共54篇一作，letter10分以上:NEJM2篇1作；Lancet1篇2作；JCO1篇1作；Gut1篇2作；Hepatology2篇1作，2篇3作；Journalofhepatology1篇1作，1篇2作；AmJGastroenterol，1篇1作…ThecomprehensiveSeminarbyAlejandroFornerandcolleagues1showsthatchronicinfectionwithhepatitisBvirus(HBV)orhepatitisCvirus(HCV)andalcoholusearethemainriskfactorsforhepatocellularcarcinoma.However,severalstudieshaveshownarelativelyhighincidenceofhepatocellularcarcinomainpatientswithmembranousobstructionoftheinferiorvenacava(MOVC;table)…Inconclusion,MOVCshouldnotbeneglectedasariskfactorforhepatocellularcarcinoma.Itdiscussesacaseofa42-year-oldwomanwhoexperiencedmilddyspnea,peripheraledema,andfatigue.ItsaysthatanabdominalcomputedtomographyandaDopplerultrasoundstudy