简介:Cisplatindamagescochlearhaircellsandspiralganglionneuronsthroughcelldeathsignalingpathwaysthatarenotfullyunderstood.Weusedfocusedapoptosisgenemicroarraystostudyearlychangesingeneexpres-sionincochlearculturesfromP3neonatalratstreatedwithcisplatin(0.2mM).After12hoursofcisplatintreat-ment,morethan50%ofthe96genesonthearrayshowedasignificantdecreaseinexpression,consistentwithwidespreadcelldeath.However,after3hoursofcisplatintreatment,10genesshowedsignificantincreaseinex-pressionintotalcochleartissue.Inexperimentswithsubsetsofcochleartissues,at3h,cisplatininducedincreasedexpressionof12genesinthecochlearsensoryepithelium(basilarmembrane)and11genesinthespiralganglion(tissueofRosenthal'scanal,containingthespiralganglion).Theseincludedpro-andanti-apoptoticgenesin-volvedinthep53signalingpathway,TNFreceptorfamily,NF-kappaBpathway,deathdomainfamily,deatheffec-tordomainfamily,Bcl-2family,CARDfamily,TRAFfamily,andGTPsignaltransduction.Althoughthechangesingeneexpressionshowedanoverlapbetweenbasilarmembraneandspiralganglion,otherchanges,whichmayreflecttheuniqueresponseofeachtissue,werealsoobserved.Pifithrin-αblockedcisplatin-inducedup-regulationofgenesinthep53signalingpathwaywhenassayedbybothsuperarrayandrealtimePCR.Thedataaddtoourunderstandingoftheinvolvementofp53incisplatin-inducedototoxicityandotoprotection,conferredbythep53inhibitorPifithrin-α.
简介:NuclearfactorkappaB(NF-κB)isoneofthebest-characterizedtranscriptionfactorsplayingimportantrolesinmanycellularresponsestoalargevarietyofstimuli,includinginflammatorycytokines,phorbolesters,growthfactors,andbacterialandviralproducts.TheaimofthisstudyistodemonstrateNF-κBexpressioninthemousecochleaanditsenhancementinresponsetolipopolysaccharides(LPS)andkanamycin(KA)treatment.MethodsKAtreatmentconsistedofsubcutaneousKAinjectionsat700mg/kgtwiceadaywithaneight-hourintervalbetweenthetwoinjectionsfor3or7days.ForanimalsintheLPStreatmentgroup,asingledoseof0.3mgLPSdissolvedin0.2mlsterilesalinewereinjectedintobothbullaethroughthetympanicmembraneandkepttherefor3hours.Animalsinthecontrolgroupreceivedsubcutaneoussalineinjectionfor7days.Followingimmmunohistochemichalprocessingwithrabbitpolyclonalanti-NF-κBp65antibodies,cryosectionsofthecochleawereexaminedforexpressionofNF-κBp65invariousstructuresinthecochlea.ResultsNF-κBp65expression,identifiedbypresenceofbrownreactionproductscharacteristicofDABimmunohistochemistry,wasvisibleinthespiralligament,spiralprominence,tectorialmembrane(TM),spiralganglionandnervefibers.RelativelyweakNF-κBp65expressionwasalsovisualizedintheorganofCorti.WithintheorganofCorti,theinnerhaircells(IHC),outerhaircells(OHC),innerpillarcells(IP),outerpillarcells(OP),Deiter'scells(DC),andBoettcher'scellsexhibitedstrongerstainingthantheinnersulcuscells,Hensen'scells(HC)andClaudius'cells.NoNF-κBp65expressionwasseeninthenucleusoftheIHCandOHC.NF-κBp65expressionwasincreasedinanimalsexposedtoLPSorKA,demonstratingsignificantdifferencesinthestainingbetweencontrolanimalsandLPS/KA-treatedanimals.NF-κBp65expressionwasnotsignificantlydifferentbetweenLPStreatedandKAtreatedanimalsorbetween3and7daysinKA-treatedanimals.Conclusio
简介:ObjectiveAlongwithchangesintheecologysystemandundertheinfluenceofvariousenvironmentalfactors,theincidenceoftumorhasbeenincreasingyearafteryear.Thereisatrendincancertherapytomovetocombinedtherapiesinvolvingsurgery,radiationchemotherapyandgenetherapy.Cancergenetherapyinrecentyearshasbroughtnewopportunitiesfortreatmentoftumor.Itsadvantagesincludelowrateoftolerance,insensitivitytocellcycles,highspecificityandcoverageforbothprimaryandmetastatictumors1,2.However,thisisanewfieldofclinicalresearch.RegardingthecorrelationamongtheSTAT3,CyclinD1andP21genesandtumors,researchhasfocusedontheirexpressionandregulation.Thisarticleprovidesasummaryofrelatedresearch.
简介:Background:Currently,thereisasignificantlackofdataconcerninglong-termoutcomesfollowingpaediatriccochlearimplantationintermsofqualityoflife.Thereisaneedforalong-term,prospectivestudyinthisregard.Thisstudyaimsathighlightingthepreliminaryresults,oneyearpostsurgeryofafiveyearprospectivestudy.Methods:TheCochlearTMPaediatricImplantedRecipientObservationalStudy(P-IROS)isaprospective,patientoutcomesregistryforroutinelyimplantedchildren.Thestudycollectsdatausingquestionnairespost-surgeryandatregularintervalsuptofiveyears.Results:AtourCentre,159cochlearimplantsurgeryprocedureswerecarriedoutbetweenJanuary2014andDecember2014.CategoryofAuditoryPerformanceIIscoreincreasedfrom‘0’to‘3’atsixmonthsandto‘5’at12monthsforchildrenaged0—3years,althoughthiswasnotstatisticallysignificant.However,thesametrendwasstatisticallysignificantfortheage3—6yearandage6—10yearbrackets.Thequalityoflifeofthechildimprovedsignificantly.Analysisofcommunicationmoderevealedastatisticallysignificantoverallshifttotheauditory-oralmodefromtotalcommunication.Conclusion:Cochlearimplantationisalife-changingintervention.Theevidenceinsupportofwhatitcanachievesafelyisclear.However,thecostsassociatedwithitraisethequestionifitwillremainaneffectiveoptionforlifeinallchildren.TheCochlearP-IROSisanattempttoanswerthesameoverafiveyearperiod.OurstudyinNewDelhi,sofarconcludesthatcochlearimplantationinapopulationwithlimitedaccesstofundsisveryeffective,oneyearaftersurgery.
简介:目的考察3~5岁听障儿童的气质特点及其影响因素,为康复训练提供参考依据。方法选取111名3~5岁听障儿童,采用3~7岁儿童气质问卷施测。结果3~5岁听障儿童在气质各维度上的表现倾向不同(P〈0.05),适应度维度得分最高,其次为趋避性、心境、注意分散度和规律性,注意力持久性和反应阂得分最低。儿童性别、主要照顾人及其受教育水平、职业、家庭结构对听障儿童气质的多个维度具有显著影响(P〈0.05),主要表现在反应强度、注意力持久性、规律性、注意分散度、活动量、心境和适应度维度;助听设备和康复时间对听障儿童气质特点影响不明显(P〉0.05)。结论3~5岁听障儿童的气质受家庭、社会环境等多方面因素影响,但在具体特征上有其独特性。
简介:摘要目的探讨UF1000i尿沉渣分析仪和超高倍显微镜在尿红细胞形态检测分析中的应用价值。方法选取住院与门诊血尿标本217例,对同例样本分别采用UF-1000i尿沉渣分析仪与超高倍显微镜检测,分析尿液中红细胞的形态。结果UF-1000i尿沉渣分析仪与超高倍显微镜检测结果准确率较高,且两种方法之间均无差异性。结论UF-1000i尿沉渣分析仪和超高倍显微镜需结合使用,以克服两种方法的缺陷,提高检测的准确性,从而为临床诊断提高确切依据。
简介:目的研究10号染色体缺失张力蛋白磷酸酶(phosphataseandtensinhomologuedeletedonchromosometen,PTFEN)、磷酸化Akt(P—Akt)及核转录因子-KB(NF—KB)在中耳胆脂瘤上皮中的表达,探讨P13K(phos—phatidylinositol-3-kinase,磷脂酰肌醇-3激酶)-Akt信号通路在中耳胆脂瘤上皮细胞过度增殖机制中的可能作用。方法采用免疫组织化学SP法(辣根酶标记链霉卵白素连接法,streptavidin—peroxidaseconjugatedmethod)检测30例中耳胆脂瘤组织标本与15例正常外耳道皮肤标本中PTEN、P—Akt及NF—KB蛋白的表达。结果PTEN蛋白阳性表达主要定位于上皮细胞核,其在中耳胆脂瘤上皮中阳性表达率为36.7%,明显低于正常外耳道皮肤组的9313%(P〈0.01);P—Akt蛋白阳性表达主要定位于上皮细胞胞质,其在中耳胆脂瘤上皮中阳性表达率为70.0%.明显高于正常外耳道皮肤组的26.7%(P〈0.01);NF—KB蛋白阳性表达定位于上皮细胞核.其在中耳胆脂瘤上皮中阳性表达率为63-3%,明显高于正常外耳道皮肤组的20.0%(P〈0.01)。在30例中耳胆脂瘤上皮组织中,PTEN分别与P—Akt、NF—KB蛋白的表达之间呈显著负相关(P〈0.01),而P—Akt和NF—KB蛋白的表达呈显著正相关(P〈0.01)。结论PTEN、P-Akt和NF—KB在中耳胆脂瘤上皮的异常表达可能在胆脂瘤的发生、发展过程中起重要作用。胆脂瘤上皮中P13K—Akt信号通路的激活可能参与了胆脂瘤上皮细胞过度增殖机制。
简介:ObjectiveChronictinnitusisahighlyprevalentconditionandhasbeenhypothesizedtoresultfromaninnatedisturbanceincentralnervousserotonergictransmission.Giventhefrequentcomorbiditywithmajordepressionandanxiety,wearguethatcandidategenesforthesedisordersarelikelytooverlap.Thepresentstudyaddressesthegeneencodingforthe5-HT1Areceptorasaputativeriskfactorfortinnitus.MethodsIn88subjectswithadiagnosisofchronicsubjectivetinnituswhounderwentadetailedneurootologicalexamination,theentire5-HT1AgenewasamplifiedusingoverlappingPCRproducts.Ampliconswerecustomsequencedbidirectionallyandwerescreenedforvariantsinmultiplealignmentsagainstthehumangenomereference.ResultsWeidentifiedasynonymousC>Texchangeatresidue184(Pro)in7/88subjects,butdetectednomissensevariantsinthepopulationunderstudy.Specifically,thefollowingresidueswerefullyconserved:16(Pro),22(Gly),28(Ile),98(Val),220(Arg),267(Val),273(Gly),and418(Asn).DiscussionThepresentdatacountagainstthecausationofchronictinnitusbyachangeinthe5-HT1Areceptor'saminoacidsequence.However,theallelefrequencyforthe184Prominorallele(0.04)reachedtwicethefrequencyreportedincontrolcohortsfromthesameethnicity.Additionalinvestigationsareinvitedtoclarifytheroleofthe5-HT1Apolymorphisminlargersamples,andtocontrolforcomorbidaffectivedisorders.
简介:目的:探讨中国人X连锁Alport综合征患者的听力表型与皮肤组织Ⅳ型胶原α5链表达的关系。方法收集2008年8月至2013年8月期间确诊为X连锁Alport综合征的31例患者临床资料,采用纯音听阈测试或ABR+40Hz相关电位检查+声导抗+耳声发射的方式进行听力评估,并采用免疫组化染色检测皮肤组织基膜Ⅳ型胶原α5链的表达,采用Pearson相关分析方法分析二者的关系。结果31例X连锁Alport综合征中听力下降患者均表现为轻、中度感音神经性聋。听觉损害共28例(90.3%),其中22例男性中中度12例,轻度5例,轻微损害5例;女性6例,轻度3例,轻微损害3例。按皮肤Ⅳ胶原α5链染色分级,阴性17例均为男性,其中听力正常4例(3例OAE异常),听力下降13例(轻度4例,中度9例);大部阴性与可疑阳性各1例,均为男性,分别为中度和轻度;连续±2例(男性),正常和中度各1例;间断阳性3例均为女性,均为正常或轻度;连续++7例(男3,女4),其中听力正常4例,听力下降3例(2例轻度,1例中度)。染色阴性的11例听力下降患者听阈与年龄呈正相关(P=0.043,r=0.616)。结论X连锁Alport综合征患者皮肤组织Ⅳ胶原α5链的表达男性低于女性,听力表现与皮肤组织Ⅳ胶原α5链的表达有一定的关系,其中Ⅳ胶原α5链表达阴性的患者听力下降程度与年龄存在相关性,但也存在听力正常的患者,说明还有其他因素影响患者的听力。皮肤组织中Ⅳ胶原α5链表达在一定程度上能反映耳蜗基底膜中Ⅳ胶原α5链的表达和功能。