简介：Ovariancanceristhesecondmostlethalgynecologicalcancerworldwideandwhilemostpatientsrespondtoinitialtherapy,theyoftenrelapsewithresistantdisease.Humanepidermalgrowthfactorreceptors(especiallyHER1/EGFRandHER2/ERBB2)areinvolvedindiseaseprogression;hence,strategiestoinhibittheiractioncouldproveadvantageousinovariancancerpatients,especiallyinpatientsresistanttofirstlinetherapy.Monoclonalantibodiesandtyrosinekinaseinhibitorsaretwoclassesofdrugsthatactonthesereceptors.Theyhavedemonstratedvaluableantitumoractivityinmultiplecancersandtheirpossibleuseinovariancancercontinuestobestudied.Inthisreview,wediscussthehumanepidermalgrowthfactorreceptorfamily;reviewemergingclinicalstudiesonmonoclonalantibodiesandtyrosinekinaseinhibitorstargetingthesereceptorsinovariancancerpatients;andproposefutureresearchpossibilitiesinthisarea.

简介：Objective:Tostudytheexpressionofactivatedepi-dermalgrowthfactorreceptor(EGFR)andtranscrip-tionfactorE2F(E2F)inCondylomaAccuminata(CA)patients.Methods:ImmunofluorescenttechniqueswereusedtoinvestigatetheexpressionofactivatedEGFRandE2FinCApatients.Results:TheexpressionofactivatedEGFRonthemembraneofepithelialcellsinCAlesionswassig-nificantlygreatercomparedtoexpressionleversinthecontrolgroup(P<0.01).Moreover,theco-expres-sionofactivatedEGFRandE2Fwassignificantlyin-creasedcomparedtothecontrolgroup(P<0.01).Conclusion:Ourobservationssuggestthatthein-creaseinactivatedEGFRexpressionmaystimulatehyperplasiainCApatientsthroughtheactivationoftranscriptionfactorE2F.

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简介：AbstractNearly 70% of breast cancer (BC) is hormone-receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, and endocrine therapy is the mainstay of treatment for this subtype. However, intrinsic or acquired endocrine resistance can occur during the endocrine treatment. Based on insights of endocrine resistance mechanisms, a number of targeted therapies have been and continue to be developed. With regard to HR-positive, HER2-negative advanced BC, aromatase inhibitor (AI) is superior to tamoxifen, and fulvestrant is a better option for patients previously exposed to endocrine therapy. Targeted drugs, such as cyclindependent kinases (CDK) 4/6 inhibitors, mammalian target of rapamycin (mTOR) inhibitors, phosphoinositide-3-kinase (PI3K) inhibitors, and histone deacetylase (HDAC) inhibitors, play a significant role in the present and show a promising future. With the application of CDK4/6 inhibitors becoming common, mechanisms of acquired resistance to them should also be taken into consideration.

简介：Topreparemonoclonalantibodyspecifictoepidermalgrowthfactorreceptor(EGFR)intracellulardomain,itsgenewasamplifiedfromtotalRNAofA431cellbyRT-PCR.ThenthegenewasclonedintoprokaryoticvectorpET30a(+).TherecombinantplasmidwastransformedintoE.ColiBL21(DE3)strainforproteinexpression.RecombinantproteinwasinducedwithIPTGandpurifiedusingNi2+-NTAagarose.Thentheanti-EGFRmonoclonalantibody(nAb)waspreparedwithclassicalhybridomatechnique.Positivecloneswereselectedusingindirectenzyme-linkedinmunoabsorbentassay(ELISA).Totally4hybridomacloneswereobtainedandthesemAbswereIgG1(3clones)andIgG2a(1clone),respectively.Theirlightchainswereallkappachains.WesternblottinganalysisandconfocalimmunofluorescenceassaysdemonstratedthatmAbscouldspecificallyrecognizeEGFRexpressingonA431carcinomacellline.ThemAbswillbeusefulinthestudyofEGFR-mediatedsignaltransduction.

简介：Objective:Toinvestigatetheproliferativeeffectofkeratinocytegrowthfactor(KGF-2)onhumanadultkeratinocytes.Methods:Thestandardmediumwaskeratinocytegrowthmediumwithoutbovinepituitaryextract(BPE),hydrocortisoneorepidermalgrowthfactor(EGF).Keratinocytesfroma48-year-oldsubjectwereculturedandseededondisheswithstandardmediumofEGFincelldensityof2×104/32mm2.After24hours,themediumwasreplacedbythestandardmediumwith0,4,16,125and500ng/mlKGF-2,respectively.ThestandardmediumwithEGFwasusedasthepositivecontrolandthestandardmediumwithoutEGForKGF-2wasusedasthenegativecontrols.Thegrowthofkeratinocyteswasmonitoredby3-(4,5-dimethythiazol-2-yl)-2,5dipheyltetrazoliumbromide(MTT)assayandbyphotographsondays3,5and7,respectively.Results:KGF-2inconcentrationsof4-500ng/mlshowedasignificantproliferativeeffectondays5and7ascomparedwiththatofthenegativecontrols(P<0.01).Onday3thecellswereproliferatedto1.5-2.5-fold,onday5to3-5-foldandonday7to3-12-foldinKGF-2mediumasthatofthenegativecontrols.TheoptimalresponseoccurredwhentheconcentrationofKGF-2was125ng/mlonday7.CellproliferationwasalsoconsistentlyhigherinallKGF-2concentrationsascomparedwiththatofthepositivecontrols.Conclusions:KGF-2hassignificanteffectsontheproliferationofadultkeratinocytes,whicharemoreeffectivethanthatofEGF.ThisstudysupportsKGF-2canimprovethehealingofchronicwoundsinadultsinclinic.

简介：ToexploretherelationshipbetweensubstanceP(SP)releasedfromperipheralnerveendingsandtheexpressionofepidermalgrowthfactor(EGF)andepidermalgrowthfactorreceptor(EGFR)duringwoundhealing.Methods:FiftyWistarratswererandomlydividedinto2groups,injurygroupandcapsaicingroup.Intheinjurygroup,afull-thicknessskinwoundonthebackoftheratwastaken.Thewoundedgeandgranulationtissuesweretakenonthe1st,3rd,6th,9th,12thdaysafterinjury,respectively.Inthecapsaicingroup,capsaicinwasinjectedsubcutaneouslyonthebackoftheratstodestroythesensorynervetopreventthesecretionofSP,thenawoundandsamplewasmadeinthesameway.ImmunohistochemistryandinsituhybridizationwereemployedtodetecttheexpressionofSP,EGF/EGFR,andEGFmRNA/EGFRmRNAinthegranulationtissues.Results:Intheinjurygroup,immunohistochemicalstainofSPandEGF/EGFRwaslocatedonthehairfolliclesandsebaceousglandsatthe1stday.AndthestainofSPwasobviousatthe3rddayinthegranulationtissues,thendecreasedgradually.EGF/EGFRwasatlowlevelatthe3rdday,thenincreasedgraduallyandreachedthepeakatthe9thday,thendeclined.Inthecapsaicingroup,theimmunohistochemicalstainofSPandEGF/EGFRwasfaintandwithoutobviouschangeduringthewoundhealingprocess.ThetendencyoftheEGFmRNA/EGFRmRNAexpressionwassimilartothatofEGF/EGFR.Conclusions:Duringwoundhealing,SPmaypromotethehealingprocessbyaffectingtheexpressionofEGF/EGFRinthegranuationtissues.

简介：AbstractBackground:Breast cancer with low-positive human epidermal growth factor receptor 2 (HER2) expression has triggered further refinement of evaluation criteria for HER2 expression. We studied the clinicopathological features of early-stage breast cancer with low-positive HER2 expression in China and analyzed prognostic factors.Methods:Clinical and pathological data and prognostic information of patients with early-stage breast cancer with low-positive HER2 expression treated by the member units of the Chinese Society of Breast Surgery and Chinese Society of Surgery of Chinese Medical Association, from January 2015 to December 2016 were collected. The prognostic factors of these patients were analyzed.Results:Twenty-nine hospitals provided valid cases. From 2015 to 2016, a total of 25,096 cases of early-stage breast cancer were treated, 7642 (30.5%) of which had low-positive HER2 expression and were included in the study. After ineligible cases were excluded, 6486 patients were included in the study. The median follow-up time was 57 months (4-76 months). The disease-free survival rate was 92.1% at 5 years, and the overall survival rate was 97.4% at 5 years. At the follow-up, 506 (7.8%) cases of metastasis and 167 (2.6%) deaths were noted. Multivariate Cox regression analysis showed that tumor stage, lymphvascular invasion, and the Ki67 index were related to recurrence and metastasis (P < 0.05). The recurrence risk prediction model was established using a machine learning model and showed that the area under the receiving operator characteristic curve was 0.815 (95% confidence interval: 0.750-0.880).Conclusions:Early-stage breast cancer patients with low-positive HER2 expression account for 30.5% of all patients. Tumor stage, lymphvascular invasion, and the Ki67 index are factors affecting prognosis. The recurrence prediction model for breast cancer with low-positive HER2 expression based on a machine learning model had a good clinical reference value for predicting the recurrence risk at 5 years.Trial registration:ChiCTR.org.cn, ChiCTR2100046766.

简介：AIM:Toinvestigatethemorphologicalalteringeffectoftransforminggrowthfactor-β2(TGF-β2)onuntransfectedhumancornealendothelialcells(HCECs)invitro.METHODS:AfteruntransfectedHCECsweretreatedwithTGF-β2atdifferentconcentrations,themorphology,cytoskeletondistribution,andtypeIVcollagenexpressionofthecellswereexaminedwithinvertedcontrastlightmicroscopy,fluorescencemicroscopy,immunofluorescenceorWesternBlot.RESULTS:TGF-β2attheconcentrationof3-15μg/LhadobviouslyalterativeeffectsonHCECsmorphologyindoseandtime-dependentmanner,and9μg/Lwasthepeakconcentration.TGF-β2(9μg/L)alteredHCEcellmorphologyaftertreatmentfor36h,increasedthemeanopticaldensity(P<0.01)andthelengthofF-actin,reducedthemeanopticaldensity(P<0.01)ofthecollagentypeIVinextracellularmatrix(ECM)andinducedtherearrangementofF-actin,microtubuleincytoplasmandcollagentypeIVinECMaftertreatmentfor72h.·CONCLUTION:TGF-β2hasobviouslyalterativeeffectonthemorphologyofHCECsfrompolygonalphenotypetoenlargedspindle-shapedphenotype,indoseandtime-dependencemannerbyinducingmore,elongationandalignmentofF-actin,rearrangementofmicrotubuleandlargerspreadareaofcollagentypeIV.

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简介：AIM:Toestablishtheratmodelofstreptozotocin(STZ)induceddiabeticretinopathy(DR),whichisthemostcommoncauseofvisuallossandblindnessinpatientswithdiabetes,andobservethegeneexpressionofvascularendothelialgrowthfactor(VEGF)anditsreceptorsduringthedevelopmentofDR.METHODS:AratmodelofdiabeteswasestablishedbyintraperitonealinjectionofSTZ.Thediabeticratswerehousedfor2,3and4monthsafterthedevelopmentofdiabetes.Retinalhistopathologicalobservationwasperformed.TheretinalvesselswereobservedbyimmunofluorescencestainingbyCD31.ThemRNAexpressionofVEGF,VEGFreceptor1and2(VEGFR1/2)inratretinawasdetectedbyreversetranscriptionpolymerasechainreaction(RT-PCR)analysis.RESULTS:Retinalhistopathologicalobservationshowedthemorphologicalchangesofinnernuclearlayer(INL)andouternuclearlayer(ONL)atanytime-point,andalsodemonstratedtheincreasednewvesselsatboth3,4monthsafterthedevelopmentofdiabetes.TheCD31stainingresultsshowedthatthenumberofvesselswasincreasedintheretinasofdiabeticratsatboth3and4monthsafterthedevelopmentofdiabetes.Ascomparedtothenormalrats,themRNAexpressionofVEGFwasincreasedinretinasofdiabeticratsat3monthsafterthedevelopmentofdiabetes,whileVEGFR1andVEGFR2mRNAexpressionwasincreasedat2,3and4monthsafterthedevelopmentofdiabetes.CONCLUSION:Takentogether,ourresultsdemonstratedthatDRwasoccurredat3monthsafterthedevelopmentofdiabetes,andthemRNAexpressionofVEGF,VEGFR1andVEGFR2wereincreasedintheprocessofDR.ThepresentstudyfurtherevidencedtheinvolvementofVEGFanditsreceptorsintheprocessofDR.

简介：ObjectivesToinvestigatetheeffectsoftestosteroneenanthate(TE)onserumlipidsandlipoproteinsmetabolismandtheexpressionofandrogenreceptor(AR),estrogenreceptorbeta(ER-β)andplateletderivedgrowthfactorbeta(PDGFR-β)inaorticvascularsmoothmuscletissues(VSMTs).MethodsFortyagedmaleratswererandomlydividedinto4groups,groupA(placebogroup),groupB(2.5mg/kgintramuscularinjectionofTEonceaweek),groupC(5.0mg/kgintramuscularinjectionofTEonceaweek),groupD(10.0mg,/kgintramuscularinjectionofTEonceaweek).Allanimalswerefedfreelyduring16-weektreatmentperiods.TheexpressionofAR,ER-βandPDGFR-βwerestudiedbyWesternbolt.ResultsAverageserumLDL-CwasloweringroupDthanthatingroupA(p＜0.01).Comparedwiththeothergroups,averageserumTCwasalsoloweringroupD(p＜0.05).ARexpressioninaorticvascularsmoothmuscletissuescouldberegulatedbyTE:99.50±21.74,125.38±28.68and101.98±15.42forTEconcentrationsat2.5mg/kg,5.0mg/kgand10.0mg/kg,respectively,theexpressionofER-βcouldberegulatedbyTE:92.34±18.68,47.72±18.12,82.13±23.50,andtheexpressionofPDGFR-βcouldberegulatedaswellbyTE:219.70±45.59,50.16±9.72,125.36±15.74(DataforAR,ER-βandPDGFR-βproteinbandintensitywereexpressedwithx±s,withcontrolgrouptakenas100).ConclusionsThisstudyindicatesthatandrogenshavesignificanteffectsonserumlipidsandlipoproteinmetabolism.Testosteroneenanthateat5.0mg/kgcanstimulatetheexpressionofAR,butinhibitetheexpressionofPDGFR.Testosteroneenanthateattheconcentrationsof5.0mg/kgand10.0mg/kgcaninhibitetheexpressionofER-β.

简介：AbstractObjective:The role of Vitamin D-binding protein (DBP) in preeclampsia (PE) pathogenesis is unknown. In this study, we compared the expression of DBP in the placentas of PE patients with the placentas of normotensive pregnant women with placenta previa controls, and aimed to explore the effect of DBP on endothelial cells (ECs) and the underlying mechanism.Methods:DBP expression in placental tissues collected from PE patients and controls was evaluated by immunohistochemistry. The downregulation and upregulation of DBP expression in HTR-8/SVneo cells were examined using DBP-targeting small interfering RNA (siRNA) and DBP-expression vector, respectively. The conditioned media of these DBP-overexpressing and DBP-siRNA HTR-8/SVneo cells were collected and added to human umbilical vein EC (HUVEC) cultures. Angiogenic effects on HUVECs were assessed by tube formation assays, and the proliferation and migration of HUVECs were examined using the Real-Time Cell Analyzer. The expression of vascular endothelial growth factor (VEGF) and VEGF receptor (VEGFR)-2, as well as the phosphorylation of different residues of VEGFR-2 in HUVECs, were determined by western blotting.Results:DBP expression was significantly increased in the placental tissues collected from PE patients. The conditioned medium of DBP-overexpressing HTR-8/SVneo cells potently inhibited tube formation by HUVECs, in addition to their proliferation and migration. Furthermore, treatment of HUVECs with the conditioned medium of DBP-overexpressing HTR-8/SVneo cells decreased the phosphorylation of VEGFR-2 at tyrosine 996, whereas the treatment of these cells with the conditioned medium of DBP-siRNA HTR-8/SVneo cells increased the phosphorylation of VEGFR-2 at tyrosine 951, 996, and 1,175.Conclusions:The expression of DBP is increased in the placentas of PE patients. DBP plays potential roles in endothelial dysfunction, which contributes to PE development, by inhibiting tyrosine phosphorylation of VEGFR-2 in ECs.

简介：Themonoclonalantibodyagainstbovinerotavirus(BRV)receptor(BRV-R-mAb)wasusedtoexplorethesimilaritybetweenthereceptorsofBRVandhumanrotavirus(HRV).ELISA,dotimmunobindingassay,cellprotectionassay,solid-phaseassayandimmunohistochemistrymethodwereapplied.BRV-R-mAbboundbothanti-BRVIgGandanti-HRVIgGrespectivelyandcouldprotectMA104cellsagainstBRVandHRVchallenges.Immunohistochemistrytestshowedthattherewererotavirusreceptorsonthesurfacesoffoetalintestinal,trachealmucosaandMA104cellsmembrane.WepurifiedtherotavirusreceptorsonMA104ceils,whichcouldbindbothBRVandHRVinvitro.ItisconcludedthatBRVreceptorandHRVreceptorarehomogenousproteinsandcanberecognizedbybothBRVandHRV.

简介：探索骨头的效果的目的有带hepatocyte生长因素的adenoviral向量的导出髓的间充质的干细胞(BMSC)transfected(HGF，Ad-HGF)在灼伤创伤愈合上。从男Wistar老鼠的方法BMSC用由密度坡度centrifugation中等、与包含20%胎儿的牛的浆液(FBS)的DMEM有教养的Percoll分开被分开并且净化。当时，BMSC是有在感染(MOI)的100复合的最佳的基因transduction效率的Ad-HGF的transfected。transfection和在暂停的HGF的表示的效率被流动cytometry检测，酶分别地连接了immunosorbent试金(ELISA)。32只雌老鼠受到90慥?灳瑩吗？

简介：客观：为了与M-CSFR验证MAF-J6-1受体的抗原协会并且进一步学习M-CSF和它的受体的角色，调停了在支持白血病的房间增长的juxtacrine。方法：MAF-J6-1RRE2的Monoclonal抗体(McAb)和rhM-CSFR的polyclonal抗体(PolyAb)被准备。到M-CSFR的McAbRE2的特性被ELISA被间接ELISA，有J6-1房间殖民地形成的跨neutralizing试金和中立化测试证实。结果：到M-CSFR的净化的RE2的反应活动是超过1：16000。M-CSFR和MAF-J6-1R的禁止的活动能被RE2和anti-M-CSFR抗体堵住。到M-CSFR的RE2的反应能被M-CSFR减少。结论：到M-CSFR的RE2的特性被证实，有M-CSFR的MAF-J6-1R的抗原协会被证明。它建议M-CSF和它的受体调停了auto-juxtacrine刺激能是在白血病或nonhematological恶意的起作用的机制。

简介：Thegrowthofdevelopingcountriesisanimportanteventofhistoricsignificanceinthecurrentworld.Withthechangesoftheconditionsofthetimes,theirpoliticalandeconomicpursuits

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简介：AbstractBackground:Since its discovery in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected more than 2 180 000 people worldwide and has caused more than 150 000 deaths as of April 16, 2020. SARS-CoV-2, which is the virus causing coronavirus disease 2019 (COVID-19), uses the angiotensin-converting enzyme 2 (ACE2) as a cell receptor to invade human cells. Thus, ACE2 is the key to understanding the mechanism of SARS-CoV-2 infection. This study is to investigate the ACE2 expression in various human tissues in order to provide insights into the mechanism of SARS-CoV-2 infection.Methods:We compared ACE2 expression levels across 31 normal human tissues between males and females and between younger (ages ≤ 49 years) and older (ages > 49 years) persons using two-sided Student's t test. We also investigated the correlations between ACE2 expression and immune signatures in various tissues using Pearson's correlation test.Results:ACE2 expression levels were the highest in the small intestine, testis, kidneys, heart, thyroid, and adipose tissue, and were the lowest in the blood, spleen, bone marrow, brain, blood vessels, and muscle. ACE2 showed medium expression levels in the lungs, colon, liver, bladder, and adrenal gland. ACE2 was not differentially expressed between males and females or between younger and older persons in any tissue. In the skin, digestive system, brain, and blood vessels, ACE2 expression levels were positively associated with immune signatures in both males and females. In the thyroid and lungs, ACE2 expression levels were positively and negatively associated with immune signatures in males and females, respectively, and in the lungs they had a positive and a negative correlation in the older and younger groups, respectively.Conclusions:Our data indicate that SARS-CoV-2 may infect other tissues aside from the lungs and infect persons with different sexes, ages, and races equally. The different host immune responses to SARS-CoV-2 infection may partially explain why males and females, young and old persons infected with this virus have markedly distinct disease severity. This study provides new insights into the role of ACE2 in the SARS-CoV-2 pandemic.

简介：Osteoblastsofratculturedinvitrowerestimulatedwithpulsed50Hzelectromagneticfieldandbasicfibroblastgrowthfactor(bFGF).TheMTTmethod,flowcytometryandhistochemistrystainingwereusedtodetectcellproliferation,cellcycleandalkalinephosphatase.Theresultsindicated:afterstimulatedby1mTelectromagneticfield,thecellsaremoreabundant,havemoreSphasepercentages,2mTelectromagneticfieldhavenoevidenteffectoncells'growth;comparedwithelectromagneticfield,thecellsstimulatedbybFGFaremoreabundantandhavelargerSphaseratios.ElectromagneticfieldandbFGFhavenoeffectoncells,alkalinephosphatase.Therefore,weconcludedthatelectromagneticfieldcanenhanceosteoblastsgrowthlikesomegrowthfactorsuchasbasicfibroblastgrowthfactor,andtheosteoblasts',characteristicswasnotchanged.