简介：AbstractObjective:To identify potential early diagnostic markers for hepatitis B progression to primary liver carcinoma using routine immunological tests based on 6 cytokine combinations.Methods:Eight hundred and ninety-nine patients with hepatitis B progressing to early primary liver carcinoma admitted to and treated at Changhai Hospital, Naval Military Medical University, Shanghai, China between March 2015 and June 2017 were included in this observational study, including 666 patients with HBsAg+, HBeAb+, HBcAb+ liver carcinoma and 233 patients with HBsAg+, HBeAg+, HBcAb+ liver carcinoma. Receiver operating characteristic (ROC) curves were used to evaluate the efficiency of the different cytokine in the diagnosis of hepatocellular carcinoma in patients with hepatitis B. This study was approved by the Institutional Review Board of Changhai Hospital, Naval Military Medical University, China (approval No. CHEC2020-080) on June 6, 2020.Results:Changed levels of interleukin (IL)-1β, IL-2R, IL-8, and tumor necrosis factor (TNF)-α were statistically significant (P < 0.05). The area under the ROC curve, sensitivity, specificity, positive predictive value, negative predictive value, and Youden index for the diagnosis of primary liver carcinoma using the combination of IL-1β, IL-2R, IL-8, and TNF-α were 0.938, 79.2%, 96.7%, 96%, 82.0%, 0.759, respectively. The serum alpha-fetoprotein level in patients with primary liver carcinoma was positively correlated with IL-2R (r=0.3502, P < 0.001), IL-8 (r=0.1558, P=0.0273), and TNF-α (r=0.2544, P < 0.001) levels. The equation fitted to the results was logit(P)=0.086+ 0.01 × IL-2R-0.001 × IL-8-0.033 × TNF-α-0.041 × IL-1β.Conclusion:Our study establishes a novel, potentially valuable diagnostic model based on four cytokines related to the early stages of liver carcinoma.

简介：AbstractSurgical resection (SR) is recommended as a radical procedure in the treatment of hepatocellular carcinoma (HCC). However, postoperative recurrence negatively affects the long-term efficacy of SR, and preoperative adjuvant therapy has therefore become a research hotspot. Some clinicians adopt transcatheter arterial chemoembolization (TACE) as a preoperative adjuvant therapy in patients undergoing SR to increase the resection rate, reduce tumor recurrence, and improve the prognosis. However, the findings of the most relevant studies remain controversial. Some studies have confirmed that preoperative TACE cannot improve the long-term survival rate of patients with HCC and might even negatively affect the resection rate. Which factors influence the efficacy of preoperative TACE combined with SR is a topic worthy of investigation. In this review, existing clinical studies were analyzed with a particular focus on several topics: screening of the subgroups of patients most likely to benefit from preoperative TACE, exploration of the optimal treatment regimen of preoperative TACE, and determination of the extent of tumor necrosis as the deciding prognostic factor.

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：TostudythemechanismofinfectionofEpstein-Barrvirus(EBV)ingastriccarcinomacells,theAkataandP3HR-1strainsofEBVwereusedastheteststrainsofviruses,andthesignetringcelllineHSC-39ofgastriccarcinomacellswasusedasthetargetcellsofinfection.Thevirus-infectedcellcloneswereisolatedbylimiteddilutionmethod.ItwasfoundthattheEBV-encodedsmallRNA(EBER)couldbedetectedintheinfectedcells.TheAkataandP3HR-1EBVinfectedparentalcellsandmostofclonesexpressedEBNA1,butnotEBNA2.Latentmembraneprotein(LMP-1)andLMP-2,andtheQpromoter(p),butnottheCp/WpforEBNAgenetranscriptionwasactiveintheinfectedparentalcellsaswellasalltheclones.UninfectedHSC-39cellsdidnotexpressCD21,however,AkatabutnotP3HR-1EBV-infectedclonesex-pressedlowlevelofCD21mRNA.TheseresultsdemonstratethatHSC-39cellsaresusceptibletobothEBVstrainsandEBVinfectsHSC-39cellsthroughtheCD21-independentpathway.ThisstudydefinesasignetringtypeofgastriccarcinomacellslineasauniquetargetcellsforthestudyofEBVinfectionmechanism.

简介：Objective:TolookforthefurtherevidenceforHPVL1HPV16E6,HPV18E6andEBVascarcinogenicfactorsinlaryngealcarcinoma.Method:weexaminedrepresentativenumbersofspecimensfromlaryngealcancerwithhighlysensitivePCRtechniqueforthepresenceofHPVL1andhigh-risktypesHPV16E6,HPV18E6andEBVLMP1.Results:UsingPCRdetection,7.3%sampleswereHPVL1positive,52.03%wereHPV16E6positive,30.89%wereHPV18E6positiveand9.13%wereEBVLMP1positive.ThelowincidenceofHPVL1andhighincidenceofHPV-16E6andHPV18E6genessuggestthatHPVmightbeintegratedintotumorcells.OurresultssupportaroleofHPV-16andHPV-18infectioninthepathogenesisoflaryngealcarcinomainChina.Conclusion:IntegrationofE6intohostgenomeandstableexpressionofthesegenesmaybeassociatedwiththecarcinogenesisoflaryngealcarcinoma.HPV-16andHPV-18maysynergisticallyfunctiononthepathogenesisoflaryngealcarcinoma.Ourresultssuggestanassociationoflaryngealcarcinogenesisandinfectionwiththehigh-riskHPVtypes16,HPV18andEBV.

简介：AbstractBackground:Pre-operative non-invasive histological evaluation of hepatocellular carcinoma (HCC) remains a challenge. Tumor perfusion is significantly associated with the development and aggressiveness of HCC. The purpose of the study was to evaluate the clinical value of quantitative liver perfusion parameters and corresponding histogram parameters derived from traditional triphasic enhanced computed tomography (CT) scans in predicting histological grade of HCC.Methods:Totally, 52 patients with HCC were enrolled in this retrospective study and underwent triple-phase enhanced CT imaging. The blood perfusion parameters were derived from triple-phase CT scans. The relationship of liver perfusion parameters and corresponding histogram parameters with the histological grade of HCC was analyzed. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal ability of the parameters to predict the tumor histological grade.Results:The variance of arterial enhancement fraction (AEF) was significantly higher in HCCs without poorly differentiated components (NP-HCCs) than in HCCs with poorly differentiated components (P-HCCs). The difference in hepatic blood flow (HF) between total tumor and total liver flow (ΔHF = HFtumor -HFliver) and relative flow (rHF = ΔHF/HFliver) were significantly higher in NP-HCCs than in P-HCCs. The difference in portal vein blood supply perfusion (PVP) between tumor and liver tissue (ΔPVP) and the ΔPVP/liver PVP ratio (rPVP) were significantly higher in patients with NP-HCCs than in patients with P-HCCs. The area under ROC (AUC) of ΔPVP and rPVP were both 0.697 with a high sensitivity of 84.2% and specificity of only 56.2%. The ΔHF and rHF had a higher specificity of 87.5% with an AUC of 0.681 and 0.673, respectively. The combination of rHF and rPVP showed the highest AUC of 0.732 with a sensitivity of 57.9% and specificity of 93.8%. The combined parameter of ΔHF and rPVP, rHF and rPVP had the highest positive predictive value of 0.903, and that of rPVP and ΔPVP had the highest negative predictive value of 0.781.Conclusion:Liver perfusion parameters and corresponding histogram parameters (including ΔHF, rHF, ΔPVP, rPVP, and AEFvariance) in patients with HCC derived from traditional triphasic CT scans may be helpful to non-invasively and pre-operatively predict the degree of the differentiation of HCC.

简介：Differentialproteomeprofilesofhumanlungsquamouscarcinomatissuecomparedtopairedtumor-adjacentnormalbronchialepithelialtissuewereestablishedandanalyzedbymeansofimmobilizedpHgradient-basedtwo-dimensionalpolyacrylamidegelelectrophoresis(2-DPAGE)andmatrix-assistedlaserdesorption/ionizationtimeofflightmassspectrometry(MALDI-TOF-MS).Theresultsshowedthatwell-resolved,reproducible2-DEpatternsofhumanlungsquamouscarcinomaandadjacentnormalbronchialepithelialtissueswereobtainedundertheconditionof0.75-ugprotein-load.Theaveragedeviationofspotpositionwas0.733+0.101mminIEFdirection,and0.925+0.207mminSDS-PAGEdirection.Fortumortissue,atotalof1241±88spotsweredetected,987±65spotswerematchedwithanaveragematchingrateof79.5%.Forcontrol,atotalof1190+72spotsweredetected,and875±48spotswerematchedwithanaveragematchingrateof73.5%.Atotalof864±34spotswerematchedbetweentumorsandcontrols.Forty-threedifferentialproteinswerecharacterized:someproteinswererelatedtooncogenes,andothersinvolvedintheregulationofcellcycleandsignaltransduction.Itissuggestedthatthedifferentialproteomicapproachisvaluableformassidentificationofdifferentiallyexpressedproteinsinvolvedinlungcarcinogenesis.Thesedatawillbeusedtoestablishhumanlungcancerproteomedatabasetofurtherstudyhumanlungsquamouscarcinoma.

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简介：AbstractBackground:MicroRNA-20a (miR-20a) is dysregulated in many types of malignancies, including human hepatocellular carcinoma (HCC), but its expression level and functional significance in HCC are still disputed. We aimed to study the role of miR-20a-5p in HCC and its downstream molecular mechanisms.Methods:We used real-time polymerase chain reaction to detect the expression of miR-20a-5p and runt-related transcription factor 3 (RUNX3) in HCC and paraneoplastic tissue, transfected Huh7 and highly metastatic human hepatocellular carcinoma (MHCC97H) cells. A live cell workstation was used to observe the proliferation and migration of transfected cells. The invasiveness of transfected cells was verified by Transwell assay. Cell apoptosis was detected by flow cytometry. The expression levels of proteins after transfection were measured using simple western immunoblot measurements. Gene expression profiles between HCC and normal samples were obtained from The Cancer Genome Atlas. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment results were processed by the database for annotation, visualization and integrated discovery. Potential target genes of miR-20a-5p were predicted to further investigate how miR-20a-5p regulates epithelial-mesenchymal transition (EMT) in HCC.Results:MiR-20a-5p was significantly highly expressed in HCC tissues, and overexpression of miR-20a-5p significantly promoted HCC cell proliferation, migration, and invasion and inhibited apoptosis in vitro. The protein expression of E-cadherin was decreased and that of vimentin was increased after overexpression of miR-20a-5p in HCC cells. We discovered the intersection of genes from miRDB, miR TarBase, and TargetScan, obtained 397 target genes and finally focused on RUNX3. RUNX3 was not only reduced in HCC specimens but also drastically reduced in HCC cells overexpressing miR-20a-5p. RUNX3 expression decreased with elevated miR-20a-5p, which activated downstream EMT signaling and promoted cell proliferation, migration, and invasion.Conclusions:Since RUNX3 is involved in EMT in HCC, as proven by previous research, our findings provide further evidence for a novel regulatory pathway comprising the miR-20a/RUNX3/EMT axis that upregulates EMT signaling and enhances the migration of HCC cells.

简介：AbstractBackground:Hepatectomy for hepatocellular carcinoma (HCC) beyond the Milan criteria is shown to be beneficial. However, a high rate of post-operative HCC recurrence hinders the long-term survival of the patients. This study aimed to investigate and compare the impacts of tenofovir (TDF) and entecavir (ETV) on the recurrence of hepatitis B viral (HBV)-related HCC beyond the Milan criteria.Methods:Data pertaining to 1532 patients who underwent hepatectomy and received antiviral therapy between January 2014 and January 2019 were collected from five centers. Recurrence-free survival (RFS) analysis was performed using the Kaplan-Meier method. Cox proportional hazards regression analysis was performed to determine prognostic factors for HCC recurrence.Results:The analysis incorporates 595 HBV-related HCC patients. The overall 5-year RFS was 21.3%. Among them, 533 and 62 patients received ETV and TDF treatment, respectively. The 1-, 3-, and 5-year RFS rates were 46.3%, 27.4%, and 19.6%, respectively, in the ETV group compared with 65.1%, 41.8%, and 37.2%, respectively, in the TDF group (P < 0.001). Multivariate analysis showed that TDF treatment (hazard ratio [HR]: 0.604, P = 0.005), cirrhosis (HR: 1.557, P = 0.004), tumor size (HR: 1.037, P = 0.008), microvascular invasion (MVI) (HR: 1.403, P = 0.002), portal vein tumor thrombus (PVTT) (HR: 1.358, P = 0.012), capsular invasion (HR: 1.228, P= 0.040), and creatinine levels (CREA) (HR: 0.993, P = 0.031) were statistically significant prognostic factors associated with RFS.Conclusions:Patients with HCC beyond the Milan criteria exhibited a high rate of HCC recurrence after hepatectomy. Compared to the ETV therapy, TDF administration significantly lowered the risk of HCC recurrence.

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简介：ObjectiveToinvestigatethehypermethylationstatusofglutathionetransferaseP1(GSTP1)andE-cadherin(ECAD),TSGs(tumorsuppressorgenes)inourbreastcancersamplesandexploretheircorrelationwithclinicopathologicalfeaturesofcorrespondingcancerpatients.MethodsOnehundredandthirty-sixIDC(invasiveductalcarcinoma)patientswererecruitedforanalysisand16fibroadenomapatientsactedascontrol.DNAextractionandmethylation-specificPCR(MSP)weresubsequentlyperformedprecededbypathologicalexamination.ResultsThepercentageofhypermethylatedGSTP1incarcinomaandfibroadenomagroupswas34.92%and15.79%respectivelyandthepercentageofhypermethylatedECADincarcinomasandfibroadenomaswas18.00%and0.00%respectively.Carcinomahadthehighestpercentageofc-erbB2overexpressionbeing54.55%amongtheclinicopathologicalparameters.ConclusionHypermethylationpatternsarefrequentinIDCandseemtorelatetoc-erbB2overexpression,andsuchepigeneticchangeshouldnotbeneglectedinfibroadenoma.Tumormethylationstatusincancerpatientscanbedeterminedatearlystageanditmaybeareferenceforbettertreatmentplanning.

简介：在忍受人的上皮的裸体老鼠在下的xenotransplanted肿瘤的生长上调查dys心理的压力效果的目的卵巢的癌，和对P53和NFBp65表情的影响。

简介：Monoclonalantibody(MAb)toratlivercyto-chromeP-450jisozyme,anactivatingenzymespecifictonitrosaminemetabolism,wasusedcoupledwithimmunoblotting,densitometerscanningofSDS-PAGEgelsandimmunohistochemicaltechnique.ThetraceP-450HSjisozyme(Mr.51.5Kd)wasfoundinhumangastricmucosa.ItwassimilartoP-450jinmolecularweight,catalyticandimmunochemicalproperties.TheconcentrationsofP-450HSjinmucosaoflessercurvaturewerehigherthanthoseingreatercurvature.Thismightbeoneoftheimportantreasonsthatlessercurvatureisthecommonestareaforgastriccarcinoma.ButtherewaspossiblylessP-450HSjingastricmucosawithcancer.Im-munohistochemically,P-450HSjwasdiscoveredinthecytoplasmofsomeglandularepithelialcells,especiallyintheglandswithhyperplasticandintestinalmetaplasticchangesadjacenttocarcinoma.Itwasalsofoundinsomenormalglandsandintumorcellsofhigh-differentiatedadenocarcinoma,butnotinthoseoflow-differentia

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简介：Interleukin-12(IL-12)isacriticalcytokinerepresentingthelinkbetweenthecellularandhumoralbranchesofhostimmunedefenseapparatus.IL-12-inducedcytotoxiclymphocyte(CTL)developmentisacentralmechanisminimmuneresponsesagainstintracellularinfectiousagentsaswellasmalignantgrowth.However,themolecularbasisoftumor-specificCTLresponsesmediatedbyIL-12remainspoorlydefined.Inthisstudy,weaddressedthisissueinacomprehensivemannertoprobeintoIL-12-inducedanti-tumorresponsesbyglobalgeneexpressionprofilingofmRNAexpressioninCD8+TcellsinatransplantablesyngeneicmousemammarycarcinomamodeltreatedornotwithrecombinantIL-12.AstrongtumorregressionwasinducedbytheIL-12treatment.AnintrospectionofdifferentialgeneexpressionatanearlystageoftheIL-12-initiatedCTLactivationrevealsinterestinggenesandmolecularpathwaysthatmayaccountforthemarkedtumorregression,andislikelytoprovidearichsourceofpotentialtargetsforfurtherresearchanddevelopmentofeffectivetherapeuticmodalities.Cellular&MolecularImmunology.2004;1(5):357-366.

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简介：Objective:Toexploretherelationshipbetweenperoxisomeproliferatoractivatedreceptor-gamma(PPARγ)andperoxisomeproliferator-activatedreceptor-gammacoactivator-1(PGC-1)expressioningastriccarcinoma(GC),andanalyzetheircorrelationswithclinicopathologicalfeaturesandclinicaloutcomesofpatients.Methods:Thetwo-stepimmunohistochemicalmethodwasusedtodetecttheexpressionofPPARγandPGC-1in179casesofGC,and108casesofmatchednormalgastricmucosa.Besides,16casesoffreshGCspecimensandcorrespondingnormalgastricmucosaweredetectedforPGC-1expressionwithWesternblotting.Results:ThepositiveratesofPPARγandPGC-1expressionweresignificantlylowerinGC(54.75%,49.16%)thaninnormalgastricmucosa(70.37%,71.30%),respectively(P<0.05).ThedecreasedexpressionofPGC-1inGCwasconfirmedinourWesternblotanalysis(P=0.004).PPARγandPGC-1expressionswererelatedtoLauren’stypesofGC(P<0.05).PositivecorrelationwasfoundbetweenPPARγandPGC-1expressioninGC(rk=0.422,P<0.001).ThesurvivaltimeofPPARγnegativeandpositivepatientswas36.6±3.0vs.38.5±2.7months,andnostatisticaldifferencewasfoundbetweenthe5-yearsurvivalratesoftwogroups(34.4%vs.44.1%,P=0.522,log-ranktest);thesurvivaltimeofPGC-1negativeandpositivepatientswas36.2±2.8vs.39.9±2.9months,whilenostatisticaldifferencewasfoundbetweenthe5-yearsurvivalratesofthetwogroups(32.0%vs.48.2%,P=0.462,log-ranktest)Conclusions:DecreasedexpressionofPPARγandPGC-1inGCwasrelatedtotheLauren’sclassification.TheirexpressionsinGCwerepositivelycorrelated,indicatingthattheirfunctionsingastriccarcinogenesismaybecloselyrelated.