简介:Objective:Chroniclymphocyticleukemia(CLL)andmantlecelllymphoma(MCL)cellsover-expressaguanineexchangefactor(GEF),Rasgrf-1.ThisGEFincreasesactiveRasasitcatalyzestheremovalofGDPfromRassothatGTPcanbindandactivateRas.ThisstudyaimstostudythemechanismofactionofRasgrf-1inB-cellmalignancies.Methods:N-terminustruncatedRasgrf-1variantshaveahigherGEFactivityascomparedtothefull-lengthtranscriptthereforeaMCLcelllinewithstableover-expressionoftruncatedRasgrf-1wasestablished.TheB-cellreceptor(BCR)andchemokinesignalingpathwayswerecomparedintheRasgrf-1over-expressingandacontroltransfectedcellline.Results:Cellsover-expressingtruncatedformofRasgrf-1haveahigherproliferativerateascomparedtocontroltransfectedcells.BCRwasactivatedbylowerconcentrationsofanti-IgMantibodyinRasgrf-1over-expressingcellsascomparedtocontrolcellsindicatingthatthesecellsaremoresensitivetoBCRsignaling.BCRsignalingalsophosphorylatesRasgrf-1thatfurtherincreasesitsGEFfunctionandamplifiesBCRsignaling.ThisactivationofRasgrf-1inover-expressingcellsresultedinahigherexpressionofphospho-ERK,AKT,BTKandPKC-alphaascomparedtocontrolcells.BesidesBCR,Rasgrf-1over-expressingcellswerealsomoresensitivetomicroenvironmentstimuliasdeterminedbyresistancetoapoptosis,chemotaxisandERKpathwayactivation.Conclusions:ThisGEFproteinsensitizesB-cellstoBCRandchemokinemediatedsignalingandalsoupregulatesanumberofothersignalingpathwayswhichpromotesgrowthandsurvivalofthesecells.
简介:随着外科手术微创化时代的发展,经皮脊柱内镜技术的发展也取得了长足的进步,并逐渐走向成熟。经皮脊柱内镜技术是在YESS(yeungendoscopicspinesystem)技术基础之上逐渐发展起来的。所谓YESS技术,即美籍华人Yeung[1]于20世纪90年代研制了脊柱内镜YESS系统,并应用该系统采用后外侧入路经皮经Kambin三角进入椎间盘行髓核摘除减压的技术。Hoogland等[2]又在YESS技术基础上进行扩展改进,提出了TESSYS(transforaminalendoscopicspinesystem)技术,借助内镜直视下直接到达椎管内突出的髓核,
简介:指深屈肌腱撕脱性损伤俗称"运动衣,Jersey"损伤,常伴有肌腱止点处的撕脱骨折,是一种少见的损伤。国外报道较多,国内也偶见报道[1-2]。Leddy等[3]早在1977年就根据损伤后肌腱所在的位置,将此种损伤分为3种类型,I型:撕脱的肌腱回缩到手掌部,肌腱长短腱纽均断裂。II型:肌腱回缩到近端指间关节,短腱纽断裂,长腱纽完整,肌腱断端常带有小片撕脱骨折。III型:指屈肌腱止点处撕脱骨折,骨折片较大,常累及关节面,短腱纽完整,骨折片移位到远端指间关节。1981年,Smith[4]对此分型做了新的补充,也就是IV型,即:肌腱止点处撕脱骨折,同时肌腱又从骨折片上撕脱,并向近端回缩。2001年,Al-Qattan[5]报道了4例不同于前几型的损伤,即:屈指深肌腱止点撕脱骨折同时合并末节基底的骨折,他称之为V型损伤,并根据撕脱骨折是否涉及关节面,分为Va和Vb不同类型。2002年,潘勇卫等[1]报道的14例屈指深肌腱撕脱性损伤中有4例是此种类型的损伤。2012年10月29日,我们收治2例非运动性损伤的V型屈指深肌腱撕脱伤患者的诊断和治疗进行探讨。
简介:ThechronicinfectionofhepatitisBvirus(HBV)iscloselyrelatedtotheoccurrenceanddevelopmentofhepatocellularcarcinoma(HCC).AccumulatedevidencehasshownthatHBVXprotein(HBxprotein)isamultifunctionalregulatorwithacrucialroleinhepatocarcinogenesis.However,informationonthemechanismbywhichHBVinducesHCCislacking.ThisreviewfocusesonthepathologicalfunctionsofHBxinHBV-inducedhepatocarcinogenesis.Asatransactivator,HBxcanmodulatenuclearfactorkappa-light-chain-enhancerofactivatedBcells(NF-κB)andtranscriptionfactorAP-2.Moreover,HBxcanaffectregulatorynon-codingRNAs(ncRNAs)includingmicroRNAsandlongncRNAs(lncRNAs),suchasmiRNA-205andhighlyupregulatedinlivercancer(HULC),respectively.HBxisalsoinvolvedinepigeneticmodification,includingmethylationandacetylation.HBxinteractswithvarioussignal-transductionpathways,suchasproteinkinaseB/Akt,Wnt/β-catenin,signaltransducerandactivatoroftranscription,andNF-κBpathways.Moreover,HBxaffectscellularfatebyshiftingthebalancetowardcellsurvival.HBxmayleadtothelossofapoptoticfunctionsordirectlycontributestooncogenesisbyachievingtransformingfunctions,whichinducehepatocarcinogenesis.Additionally,HBxcanmodulateapoptosisandimmuneresponsebydirectorindirectinteractionwithhostfactors.WeconcludethatHBxhastensthedevelopmentofhepatoma.
简介:目的:探讨示指固有伸肌腱移位重建伸拇功能术后对拇指和示指功能的影响及其解剖学机制。方法对12例进行回顾性研究,男7例,女5例,年龄18~78岁,平均42.3岁,拇长伸肌腱损伤的平面为III区4例,IV区5例,V区3例。采用示指固有伸肌腱移位重建伸拇功能,术后8~83(33.5±29.9)个月进行电话随访。评价指标包括拇指和示指的功能。拇指功能评价指标:(1)患手手掌向下平置于桌面,能否主动将拇指指尖抬离桌面;(2)能否完成“挑大拇指”的动作;(3)在保持拇指掌指关节和指间关节伸直的情况下,能否完成以第一腕掌关节为支点的拇指划圈运动;(4)在拇指处于中立位时,能否较好地完成拇指指间关节屈曲动作。示指功能评价指标:(1)患手手掌向下平置于桌面时,能否主动将示指指尖单独抬离桌面;(2)在第3~5指呈握拳位时,能否将示指伸直至与手背同一平面,完成指示的动作;(3)能否完成“兰花指”的动作;(4)示指能否自如地使用鼠标,并完成连续双击左键的动作。另外,对5具成年男性尸体的前臂标本进行解剖学研究,重点测量了指总伸肌腱中示指和中指伸肌腱腱性起点的位置。结果术后所有患者都能使用患手较为顺利地完成日常生活和工作中的常用动作,年轻患者中除1例外,均恢复了原工作。12例中有11例主观评价手术疗效满意,1例表示对疗效不满意。其中有8例能完成全部4项拇指功能评价的动作,有3例可以完成拇指功能评价动作的3项,1例仅能完成拇指功能评价动作中的2项。12例均能使用示指自如地使用鼠标,有9例能够在患手手掌向下平置于桌面时主动将示指指尖单独抬离桌面。12例均能单独伸示指,完成指示动作,但仅有7例能在第3~5指呈握拳位时将示指伸直至与手背同一平面,另5例单独伸�
简介:目的探讨术前肝纤维化指数(HFI)对肝癌手术疗效及预后的影响。方法2011年4月至2015年4月,将北京大学深圳医院接受肝癌切除术的65例患者分为低指数组(HFI≤5.4)与高指数组(HFI〉5.4)。分析两组术后疗效及预后情况。结果术前资料,两组性别、年龄、谷氨酰转肽酶、透明质酸、血小板、肝功能分级、HBV-DNA拷贝量比较,差异有统计学意义(均P〈0.05)。术中、术后资料,两组肿瘤数目、肿瘤最大径、肝纤维化类型、术后血管侵犯情况、切缘情况、肝门静脉癌栓和HBVDNA变化比较,差异有统计学意义(均P〈0.05)。低指数组并发症发生率20.0%,复发率23.3%,1、3、5年生存率分别为93.0%、53.0%、53.0%;高指数组并发症发生率22.9%,复发率25.7%,1、3、5年生存率分别为72.0%、29.0%、25.7%,两组生存率比较,差异有统计学意义(P〈0.05)。肿瘤数目〉3、HFI〉5.4、肝、门静脉癌栓是肝癌术后复发的独立危险因素。结论术前肝纤维化指数对手术疗效及预后均有显著影响,是术后复发的独立危险因素。
简介:DuckhepatitisBvims(DHBV)DNAwasdetectedindifferenttumorousnodulesofduckswithhepaticmulticentriccancerorintrahepaticmetastasisbySouthernblottechnique.Among7duckswithhepatocellularcarcinomaofmultipletumornodules,thehybridizationpatternofIntegratedDHBVDNAIndifferenttumorousnoduleswasidenticalin3casesanddifferentin2cases.OnecaseshowedasimilarhybridizationpatternintwotumorousnodulesandotheronewasnegativetorDHBVDNA.IntegratedDHBVDNAwasalsoidentifiedinametastaticlungcancerofduckswithhepatocellularcarcinoma.Thehybridizationpatternofmetastasisoflungswasasthesomeasthatinprimaryhepatocellularcarcinoma.ThesamediscretehybridizationbandsInthedifferenttumorousnodulesindicatethatthesenodulesmightarisefromonetransformedcell.ThedifferenthybridizationpatternsInvarioustumorousnodulesshowthatthesetumorousnodulesmightarisefromvarioustransformedcells.Theresultssuggestthatthehyb
简介:Objective:ToassesstheeffectofantiviraltherapyforhepatitisBvirus(HBV)-relatedhepatocellularcarcinoma(HCC)afterradicalhepatectomy.Methods:Atotalof478HBV-relatedHCCpatientstreatedbyradicalhepatectomywereretrospectivelycollected.Patientsinthetreatmentgroup(n=141)receivedpostoperativelamivudinetreatment(100mg/d),whereaspatientsinthecontrolgroup(n=337)didnot.Recurrence-freesurvival(RFS)rates,overallsurvival(OS)rates,treatmentsforrecurrentHCCandcauseofdeathwerecomparedbetweenthetwogroups.Propensityscorematching(PSM)analysiswasalsoconductedtoreduceconfoundingbiasbetweenthetwogroups.Results:The1-,3-,and5-yearRFSratesdidn’tsignificantlydifferbetweenthetwogroups(P=0.778);however,the1-,3-,and5-yearOSratesinthetreatmentgroupweresignificantlyhigherthanthoseinthecontrolgroup(P=0.002).Similarresultswereobservedinthematcheddata.SubgroupanalysisshowedthatantiviraltreatmentconferredasignificantsurvivalbenefitforBarcelonaClinicalLiverCancerstageA/Bpatients.FollowingHCCrecurrence,morepeopleinthetreatmentgroupwereabletochoosecurativetreatmentsthanthoseinthecontrolgroup(P=0.031).Forcauseofdeath,fewerpeopleinthetreatmentgroupdiedofliverfailurethanthoseinthecontrolgroup(P=0.041).Conclusion:PostoperativeantiviraltherapyincreaseschancesofreceivingcurativetreatmentsforrecurrentHCCandpreventsdeathbecauseofliverfailure,therebysignificantlyprolongingOS,especiallyinearly-orintermedian-stagetumors.
简介:许多人类疾病的发生和发展可归因于一些基因的异常表达,从而导致疾病的发生。其中一部分基因是在核因子kappaB(nuclearfactor-kappaB,NF—κB)调控下进行的。NF—κ是广泛存在于哺乳动物中的转录因子,是由Sen等于1986年首先在B细胞中发现的一种核蛋白。因它能与B细胞免疫球蛋白上的K轻链基因增强子κB序列(GGGACTITCC)特异结合而得名。实际上它能与多种细胞基因的启动子和增强子序列位点发生特异性结合,并促进转录和表达,参与众多与免疫和炎症反应有关的基因转录的调控。它的异常激活或完全抑制与多种疾病的发生有关。在控制细胞增殖、凋亡、肿瘤的发生、发展和耐药问题上均起着重要的作用。因此深入探讨NF—κB在体内病理状态下的活化机制以及其与细胞、基因之间的调节作用具有重要的意义。现就NF—κB的组成、结构、激活途径以及与肿瘤的关系作一综述。
简介:Objective:Cancercellradioresistanceisastumblingblockinradiationtherapy.TheactivityinthenuclearfactorkappaB(NFκB)pathwaycorrelateswithanti-apoptoticmechanismsandincreasedradioresistance.TheIKKcomplexplaysamajorroleinNFκBactivationuponnumeroussignals.Inthisstudy,weexaminedtheinteractionbetweenionizingradiation(IR)anddifferentmembersoftheIKK-NFκBpathway,aswellasupstreamactivators,RAF1,ERK,andAKT1.Methods:Theeffectof4GyofIRontheexpressionoftheRAF1-ERK-IKK-NFκBpathwaywasexaminedinA549andH1299lungcancercelllinesusingWesternblotanalysisandconfocalmicroscopy.WeexaminedchangesinradiationsensitivityusinggenesilencingorpharmacologicalinhibitorsofERKandIKKβ.Results:IKKα,IKKγ,andIκBαincreaseduponexposuretoIR,therebyaffectingnuclearlevelsofNFκB(phospho-p65).ERKinhibitionorsiRNA-mediateddown-regulationofRAF1suppressedthepost-irradiationsurvivaloftheexaminedlungcancercelllines.AsimilareffectwasdetectedonsurvivaluponsilencingIKKα/IKKγorinhibitingIKKβ.Conclusions:ExposureoflungcancercellstoIRresultsinNFκBactivationviaIKK.ThegeneticorpharmacologicalblockageoftheRAF1-ERK-IKK-NFκBpathwaysensitizescellstotherapeuticdosesofradiation.Therefore,theIKKpathwayisapromisingtargetfortherapeuticinterventionincombinationwithradiotherapy.
简介:Objective:TodeterminewhetherInterferon-alpha-2b(IFN-α2b)canmodulatetheautophagicresponseinhepatocellularcarcinomacells.Methods:HepatocellularcarcinomacellsweretreatedwithIFN-α2b.Autophagywasassessedbyacridineorangestaining,GFP-LC3dottedassay,transmissionelectronmicroscopyandimmunoblotting.Results:AcridineorangestainingshowedthatIFN-α2btriggeredtheaccumulationofacidicvesicularandautolysosomesinHepG2cells.TheacridineorangeHepG2cellratioswere(4.3±1.0)%,(6.9±1.4)%,and(13.1±2.3)%,respectively,aftertreatmentwith100,1,000,and10,000IU/mLIFN-α2bfor48h.AmarkedlypunctatepatternwasobservedinHepG2cellstreatedwith10,000IU/mLIFN-α2bfor48h,butonlydiffuseandweaklyfluorescentGFP-LC3punctawasobservedincontrolcells.HepG2cellstreatedwith10,000IU/mLIFN-α2bfor48hdevelopedautophagosome-likecharacteristics,includingsingle-ordouble-membranevacuolescontainingintactanddegradedcellulardebris.TheBeclin1andLC3-IIproteinexpressionwasup-regulatedbyIFN-α2btreatment.Conclusion:Autophagycanbeinducedinadose-dependentmannerbytreatmentwithIFN-α2binHepG2cells,andtheBeclin1signalingpathwaywasstimulatedbyIFN-α2b.
简介:Objective:Toinvestigatephospho-(-cateninexpressioninnon-smallcelllungcancer(NSCLC)andtostudytherelationshipbetweenphospho-(-cateninexpressionandsomeclinicalpathologicalfactors.Methods:Theexpressionofphospho-(-cateninin67primaryNSCLCcasesdetectedimmunohistochemically.Results:phospho-(-cateninwasnotexpressedinnormalbronchialmucouscellandshowedcytoplasmicandnuclearexpressioninNSCLCcell.Totalpositiveexpressionratereached62.7%,andpositiveexpressionrateofnucleuswas38.8%.Thepositiveexpressionrate(87.5%)andnuclearexpressionrateofadenocarcinoma(62.5%)wereapparentlyhigherthanthoseofsquamouscellcancer(40.0%and17.1%)(P<0.01).Expressionofphospho-(-cateninhadnorelationshiptodifferentiationdegreeandlymphaticmetastasis.Thepostoperativesurvivaltimeisnotrelatedtophospho-(-cateninexpression.(Log-ranktest,P=0.9198;P=0.6274).COXmodelanalysisshowedthattumorstageanddifferentiationareindependentriskfactorstoprognosis(P=0.001;P=0.020).Conclusion:NSCLCcellsshowpositiveexpressionofphospho-(-catenin,phospho-(-cateninnuclearexpressionisrelevanttohistologicaltypes.Thereisnodifferenceinpostoperativesurvivaltimebetweenpatientswithphospho-(-cateninpositiveexpressionandpatientswithnegativeexpression,expressionofphospho-(-cateninisnotindependentriskfactortoprognosis.
简介:Objective:Toassesstheclinicalfeatures,survivalandprognosticfactorsofprimarytesticulardiffuselargeB-celllymphoma(DLBCL).Methods:Aretrospectivestudyof37patientswithprimarytesticularDLBCLwascarriedoutfromNovember2003toMay2012.Theirclinicalfeatures,survivalandprognosticfactorswereanalyzed.Results:Duringamedianfollow-upperiodof39.8months(5.4-93.0months),themedianprogression-freesurvival(PFS)was26.2months(95%CI:0-65months)andthe3-yearoverallsurvival(OS)ratewas78.4%.Withinthewholecohort,thefactorssignificantlyassociatedwithasuperiorPFSwerelimitedstage(stageI/II),lactatedehydrogenase(LDH)≤245U/L,internationalprognosticindex(IPI)≤1,primarytumordiameter<7.5cm,andpatientswhohadcompleteresponse(CR)andreceiveddoxorubicin-containedchemotherapy(P<0.05).Therewasatrendtowardsuperioroutcomeforpatientswhoreceivedcombinedtherapy(surgery/chemotherapy/radiotherapy)(P=0.055).PatientswhohadCR,primarytumordiameter<7.5cmandIPIscore≤1weresignificantlyassociatedwithlongerPFSatmultivariateanalysis.Conclusions:PrimarytesticularDLBCLhadpoorersurvival.CR,primarytumordiameterandIPIwereindependentprognosticfactors.Thecombinedtherapyoforchectomy,doxorubicin-containedchemotherapyandcontralateraltesticularradiotherapy(RT)seemedtoimprovesurvival.
简介:目的通过对比分析探讨肩峰指数与退变性全层肩袖撕裂之间的关系。方法选取我院2014年3月至2017年10月经MRI检测或肩关节镜确诊肩袖全层撕裂的患者48例为实验组,平均年龄66岁;选取同期因其它肩关节疾病(冻结肩或肩关节不稳)就诊的患者52例为对照组,平均年龄63岁。将两者基本资料进行对比,由同一名放射科医生采集所有患者的肩关节标准前后位X线片,由2名独立的骨科医师测量所有患者的肩峰指数结果,对比两组之间肩峰指数的差异并进行统计学分析。结果肩峰指数值:肩袖撕裂组平均肩峰指数0.71,对照组肩峰指数0.65,二者相比差异有统计学意义(P=0.001);肩袖撕裂患者中,女性肩峰指数为0.70,男性肩峰指数为0.69,二者相比其差异无统计学意义(P=0.150)。结论肩峰指数可有效预测老年人群中退变性全层肩袖撕裂的发生。