简介：Trimethyltin(TMT)isanoccupationalandenvironmentalhealthhazardbehavingasapotentneurotoxinknowntoaffectthecentralnervoussystemaswellastheperipheralauditorysystem.However,themechanismsunderlyingTMT-inducedototoxicityarepoorlyunderstood.ToelucidatetheeffectsofTMTonthecochlea,asingleinjectionof4or8mg/kgTMTwasadministeredintraperitoneallytoadultrats.Thecompoundactionpotential(CAP)thresholdwasusedtoassessthefunctionalstatusofthecochleaandhistologicaltechniqueswereusedtoassesstheconditionofthehaircellsandauditorynervefibers.TMTat4mg/kgproducedatemporaryCAPthresholdelevationof25-60dBthatrecoveredby28dpost-treatment.Althoughtherewasnohaircelllosswiththe4mg/kgdose,therewasanoticeablelossofauditorynervefibersparticularlybeneaththeinnerhaircells.TMTat8mg/kgproducedalargepermanentCAPthresholdshiftthatwasgreatestatthehighfrequencies.TheCAPthresholdshiftwasassociatedwiththelossofouterhaircellsandinnerhaircellsinthebasal,high-frequencyregionofthecochlea,considerablelossofauditorynervefibersandasignificantlossofspiralganglionneuronsinthebasalturn.Spiralganglionneuronsshowedevidenceofsomashrinkageandnuclearcondensationandfragmentation,morphologicalfeaturesofapoptoticcelldeath.TMT-induceddamagewasgreatestinthehigh-frequency,basalregionofthecochleaandthenervefibersbeneaththeinnerhaircellswerethemostvulnerablestructures.

简介：Axonaldegenerationisapivotalfeatureofmanyneurodegenerativeconditionsandsubstantiallyaccountsforneurologicalmorbidity.AwidelyusedexperimentalmodeltostudythemechanismsofaxonaldegenerationisWalleriandegeneration(WD),whichoccursafteracuteaxonalinjury.Intheperipheralnervoussystem(PNS),WDischaracterizedbyswiftdismantlingandclearanceofinjuredaxonswiththeirmyelinsheaths.Thisisaprerequisiteforsuccessfulaxonalregeneration.Inthecentralnervoussystem(CNS),WDismuchslower,whichsignificantlycontributestofailedaxonalregeneration.Althoughitiswell-documentedthatSchwanncells(SCs)haveacriticalroleintheregenerativepotentialofthePNS,todatewehaveonlyscarceknowledgeastohowSCs‘sense'axonalinjuryandimmediatelyrespondtoit.Inthisregard,itremainsunknownastowhetherSCsplaytheroleofapassivebystanderoranactivedirectorduringtheexecutionofthehighlyorchestrateddisintegrationprogramofaxons.Olderreports,togetherwithmorerecentstudies,suggestthatSCsmountdynamicinjuryresponsesminutesafteraxonalinjury,longbeforeaxonalbreakdownoccurs.TheswiftSCresponsetoaxonalinjurycouldplayeitherapro-degenerativerole,oralternativelyasupportiverole,totheintegrityofdistressedaxonsthathavenotyetcommittedtodegenerate.Indeed,supportingthelatterconcept,recentfindingsinachronicPNSneurodegenerationmodelindicatethatdeactivationofakeymoleculepromotingSCinjuryresponsesexacerbatesaxonalloss.Ifthisholdstrueinabroaderspectrumofconditions,itmayprovidethegroundsforthedevelopmentofnewglia-centrictherapeuticapproachestocounteractaxonalloss.

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简介：在一个关上的领域的pycnocline被强迫的外部风倾斜并且当风下时，趋于恢复到一个水平位置。如果强迫是弱的，否则内部巨浪和内部独居的波浪出现，内部湖震摆动展出，它用作一个连接串联精力到小规模的过程。与一个骚乱闭合模型一起的二维的非静水力学的代码被构造扩大以前的实验室研究。模型能复制在相应实验室实验观察的所有关键现象。模型结果进一步为相关动态进程的深入的理解用作一个全面、可靠的数据集合。比较分析显示那个非线性的术语赞成内部巨浪和随后的内部独居的波浪的产生，并且线性模型相当预言一般趋势很好。垂直边界能近似反映所有到来的波浪，当斜坡边界为小规模的内部波浪碎和精力驱散用作一个区域时。领域的时间的进化综合运动并且势能也被分析，并且结果显示大约20%起始的可得到的势能在碎的第一个内部波浪期间被失去过程。象格子拓扑学和模型初始化那样的某数字战术简短也被讨论。

简介：Thedistributionofsensorysymptomsincarpaltunnelsyndromeisstronglydependentonthedegreeofelectrophysiologicaldysfunctionofthemediannerve.Theassociationbetweencarpaltunnelsyndromeandulnarnerveentrapmentisstillunclear.Inthisstudy,wemeasuredulnarnervefunctionin82patientswithcarpaltunnelsyndrome.ThepatientsweredividedintogroupIwithminimalcarpaltunnelsyndrome(n=35)andgroupIIwithmildtomoderatecarpaltunnelsyndrome(n=47)accordingtoelectrophysiologicaldata.Sixty-oneage-andsex-matchedsubjectswithoutcarpaltunnelsyndromewereusedasacontrolgroup.Therewerenosignificantdifferencesinulnarsensorynervepeaklatenciesorconductionvelocitiesfromthe4thand5thfingersbetweenpatientswithcarpaltunnelsyndromeandthecontrolgroup.Theulnarsensorynerveactionpotentialamplitudesfromthe4thand5thfingerswerelowerinpatientswithcarpaltunnelsyndromethaninthecontrolgroup.Theratiosoftheulnarsensorynerveactionpotentialamplitudesfromthe4thand5thfingerswerealmostthesameinpatientswithcarpaltunnelsyndromeasinthecontrolgroup.Thesefindingsindicatethatinpatientswithminimaltomoderatecarpaltunnelsyndrome,thereissomeelectrophysiologicalevidenceoftractionontheadjacentulnarnervefibers.Thefindingsdonotindicateaxonaldegenerationoftheulnarnerve.

简介：研究是否特定的等位基因HLA一级(HLA--A和HLA-B)并且班II(HLA医生)是风险因素因为年龄的exudative类型的发展联系了有斑点的退化(ARMD)，HLA抗原与ARMD在正常、影响的眼睛两个都被表示。我们设计了未来的控制盒子的研究。我们与主要经典或秘密的choroidalneovascularization招募了75个病人，对ARMD第二等，并且与光力学的治疗对待。超过55岁的250个病人，没有ophthalmologic病理，为分析平淡的检查去了医院的人，被用作控制。数据的分析显示出二个组之间的重要差别。等位基因HLA-B27与ARMD断然相关(p<0.0113)。然而，我们没发现等位基因否定地联系了。因此HLA-B27是等位基因预先安排承受ARMD。

简介：TheAMDcausesadeteriorationofthecentralfieldofvisionofthehumaneyecausedbylossoffunctionofthemacula.Themaculaisthecentralpartoftheretina,thepartthatreceivesthemostfinelydetailedinformationsinceitcontainsaconsiderablenumberofdaylightsensitiveandcoloursensitivephotoreceptorcells.PeoplewithlittleskinpigmentslikeEuropeanpeoplearemorefrequentlyaffectedthanpeoplefromtheAsiancontinentforexample.ThreequartersofthepeoplewhoareaffectedbyAMDsufferfromthedry

简介：TheLy5.1mouse,alsotermedB6.SJL-PtprcaPepcb/BoyJ,isacongenicstrainwidelyusedasarecipientinanimalstudiesofbonemarrowtransplant.OurpreviousstudydocumentedthatamajorityoftypeIspiralganglionneurons(SGNs)intheapicalturnsofLy5.1miceareunmyelinatedandaggregateintoneuronalclusters,similartothespiralganglioninthehumanear.Ouabain,awellknownNa-KATPaseinhibitor,hasbeenshowntoinduceneuronaldegenerationinavarietyofneuraltissuesincludingtheadultgerbilandCBA/CaJmousespiralganglion.Here,functionalandpathologicalchangesoftheauditorynervesinyoung-adultLy5.1micewereexaminedat3,7and14daysafterouabainexposure.SimilartoobservationsinCBA/CaJmice,ouabainapplicationselectivelyremovedtypeISGNs,resultinginanimmensedeclineoftheauditorynervefunction.Hyperplasiaofglialcellswasseenintheinjuredauditorynervesat7daysafterouabainexposure.Ourdataindicatethatthe'human-like'featuresofunmyelinatedtypeISGNshavenoprotectiveimpactonthefateofSGNsafterouabainexposure.Cellsincorporatingbromodeoxyuridine(BrdU)andexpressingSox2werealsocountedintheauditorynervesofcontrolandouabain-treatedears.ThenumberofSox2+glialcellssignificantlyincreasedat3and7dayspost-treatment.Interestingly,thehighestdensityofBrdU+cellsappearedintheapicalturnoftheinjuredauditorynerveshortlyafterouabainexposure,suggestingthatthepatternofSGNlossattheapicalturninLy5.1mousemayhavesomeimpactonthereactionofnon-neuronalcellsinresponsetoacuteototoxicdrugexposureintheauditorynerve.

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简介：AIM:ToevaluatethehighsensitivityC-reactiveprotein(hsCRP),Fetuin-Aandmatrixγ-carboxyglutamateprotein(MGP)asthemainfactorsforvascularcalcificationandinflammationinserumofpatientswithadvancedage-relatedmaculardegeneration(ARMD)incomparisontohealthycontrols.METHODS:Thesubjectswere40patientswithchoroidalneovascularization(CNV)havingameanageof70.9±9.1yandamatchedgroupof49apparentlyhealthycontrolsubjects.TheARMDwasdiagnosedusingaslitlampwithsuperfieldlens,fundusphotographyandfluoresceinangiography.MeasurementofhsCRPwasdonebynephelometrymethod.LevelsofFetuin-AandMGPweremeasuredbyenzyme-linkedimmunosorbentassay(ELISA)technique.RESULTS:hsCRP[0.45(0.07-2.63)mg/Lvs0.25(0.03-1.2)mg/L,P=0.02)]andFetuin-Alevels(50.27±5.04vs44.99±10.28ng/mL,P=0.009)werehigherinthepatientsthaninthecontrolgroups.WecouldnotfindsignificantdifferenceinMGPlevelbetweentwogroups(P=0.08).TherewasnotasignificantcorrelationbetweenMGPwithFetuin-AandhsCRPamongthepatients(P=0.7,P=0.9respectively).AsignificantnegativecorrelationofhsCRPwithFetuin-Awasobservedinbothcaseandcontrolgroups(P=0.004,r=-0.33andP=0.001,r=-0.54,respectively).CONCLUSION:AlthoughourstudyshowsthatserumhsCRPandFetuin-AisincreasedinCNVpatientsaswellasnegativelycorrelatedwithbothstudygroups,theirdirectroleonpathogenesisofARMDrequiredfuturestudies.

简介：Runningisbelievedtobebeneficialforhumanhealth.Manystudieshavefocusedontheneuroprotectiveeffectsofvoluntaryrunningonanimalmodels.Therewerebothprimaryandsecondarydegenerationinneurodegenerativediseases,includingglaucoma.However,whetherrunningcandelayprimaryorsecondarydegenerationorbothofthemwasnotclear.Partialopticnervetransectionmodelisavaluableglaucomamodelforstudyingbothprimaryandsecondarydegenerationbecauseitcanseparateprimary(mainlyinthesuperiorretina)fromsecondary(mainlyintheinferiorretina)degeneration.Therefore,wecomparedthesurvivalofretinalganglioncellsbetweenSprague-Dawleyratrunnersandnon-runnersbothinthesuperiorandinferiorretinas.Excitotoxicity,oxidativestress,andapoptosisareinvolvedinthedegenerationofretinalganglioncellsinglaucoma.Sowealsousedwesternimmunoblottingtocomparetheexpressionofsomeproteinsinvolvedinapoptosis(phospho-c-JunN-terminalkinases,p-JNKs),oxidativestress(manganesesuperoxidedismutase,MnSOD)andexcitotoxicity(glutaminesynthetase)betweenrunnersandnon-runnersafterpartialopticnervetransection.Resultsshowedthatvoluntaryrunningdelayedthedeathofretinalganglioncellsvulnerabletoprimarydegenerationbutnotthosetosecondarydegeneration.Inaddition,voluntaryrunningdecreasedtheexpressionofglutaminesynthetase,butnottheexpressionofp-JNKsandMnSODinthesuperiorretinaafterpartialopticnervetransection.Theseresultsillustratedthatprimarydegenerationofretinalganglioncellsmightbemainlyrelatedwithexcitotoxicityratherthanoxidativestress;andthevoluntaryrunningcoulddown-regulateexcitotoxicitytodelaytheprimarydegenerationofretinalganglioncellsafterpartialopticnervetransection.

简介：AIM:Tocomparetheeffectivenessandsafetybetweenbevacizumabandranibizumabinthetreatmentofagerelatedmaculardegeneration(AMD)throughasystematicreviewandmeta-analysis.METHODS:Weperformedacomprehensivesearchofrandomizedcontrolledtrials(RCTs),non-RCTs,casecontrolandcohortstudiesthatcomparedbevacizumabandranibizumabusingPubMedandtheCochraneLibrary.Aftertherelateddatawereextractedbytwoinvestigatorsindependently,pooledweightedmeandifferences(WMDs)andriskratios(RRs)with95%confidenceintervals(CIs)wereestimatedusingarandom-effectsorafixed-effectsmodel.RESULTS:AtotaloffourRCTsinvolving1927patientsandelevenretrospectivecaseseriesinvolving2296patientswereincluded.Fortheprimaryoutcomes,nosignificantdifferenceswerefoundbetweenranibizumabgroupandbevacizumabgroupinvisualacuity(WMD:-0.04;95%CI:-0.08to0.00;P=0.06),bestcorrectedvisualacuity(WMD:-0.05;95%CI:-0.10to0.00;P=0.05),retinathickness(WMD:-4.69;95%CI:-13.15to3.76;P=0.86)andfovealthickness(WMD:10.91;95%CI:-14.73to36.56;P=0.40).Thepooledanalysesintheevaluationofsafetyshowedthatcomparedtobevacizumab,ranibizumabwasassociatedwithdecreasedrisksofocularinflammation(RR:0.45;95%CI:0.23to0.89;P=0.02)andvenousthromboticevents(RR:0.27;95%CI:0.08to0.89;P=0.03).However,therewerenosignificantdifferencesobservedindeaths(P=0.69)andarterialthromboembolicevents(P=0.71)betweenthetwogroups.CONCLUSION:Withequalclinicalefficacy,ranibizumabwasfoundtobeassociatedwithlessadverseeventscomparedtobevacizumab,indicatingthatranibizumabmightbeasafermanagement.

简介：Age-relatedmaculardegeneration(AMD)causesirreversiblelossofcentralvisionforwhichthereisnoeffectivetreatment.IncipientpathologyisthoughttooccurintheretinaformanyyearsbeforeAMDmanifestsfrommidlifeonwardstoaffectalargeproportionoftheelderly.Althoughgeneticaswellasnon-genetic/environmentalrisksarerecognized,itscomplexaetiologymakesitdifficulttoidentifysusceptibility,orindeedwhattypeofAMDdevelopsorhowquicklyitprogressesindifferentindividuals.HerewesummarizetheliteraturedescribinghowtheAlzheimer's-linkedamyloidbeta(Aβ)groupofmisfoldingproteinsaccumulateintheretina.ThediscoveryofthiskeydriverofAlzheimer'sdiseaseinthesenescentretinawasunexpectedandsurprising,enablinganaltogetherdifferentperspectiveofAMD.WearguethatAβfundamentallydiffersfromothersubstanceswhichaccumulateintheageingretina,anddiscussourlatestfindingsfromamousemodelinwhichphysiologicalamountsofAβweresubretinally-injectedtorecapitulatesalientfeaturesofearlyAMDwithinashortperiod.OurdiscoveriesaswellasthoseofotherssuggestthepatternofAβaccumulationandpathologyindonoraged/AMDtissuesarecloselyreproducedinmice,includinglate-stageAMDphenotypes,whichmakesthemhighlyattractivetostudydynamicaspectsofAβ-mediatedretinopathy.Furthermore,wediscussourfindingsrevealinghowAβbehavesatsingle-cellresolution,andconsiderthelong-termimplicationsforneuroretinalfunction.WeproposeAβasakeyelementinswitchingtoadiseasedretinalphenotype,whichisnowbeingusedasabiomarkerforlatestageAMD.

简介：AbstractPurpose:Wallerian degeneration (WD) is an antegrade degenerative process distal to peripheral nerve injury. Numerous genes are differentially regulated in response to the process. However, the underlying mechanism is unclear, especially the early response. We aimed at investigating the effects of sciatic nerve injury on WD via CLDN 14/15 interactions in vivo and in vitro.Methods:Using the methods of molecular biology and bioinformatics analysis, we investigated the molecular mechanism by which claudin 14/15 participate in WD. Our previous study showed that claudins 14 and 15 trigger the early signal flow and pathway in damaged sciatic nerves. Here, we report the effects of the interaction between claudin 14 and claudin 15 on nerve degeneration and regeneration during early WD.Results:It was found that claudin 14/15 were upregulated in the sciatic nerve in WD. Claudin 14/15 promoted Schwann cell proliferation, migration and anti-apoptosis in vitro. PKCα, NT3, NF2, and bFGF were significantly upregulated in transfected Schwann cells. Moreover, the expression levels of the β-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK signaling pathways were also significantly altered.Conclusion:Claudin 14/15 affect Schwann cell proliferation, migration, and anti-apoptosis via the β-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK pathways in vitro and in vivo. The results of this study may help elucidate the molecular mechanisms of the tight junction signaling pathway underlying peripheral nerve degeneration.

简介：ASchwanncellhasregenerativecapabilitiesandisanimportantcellintheperipheralnervoussystem.ThismicroarraystudyispartofabioinformaticsstudythatfocusesmainlyonSchwanncells.Microarraydataprovideinformationondifferencesbetweenmicroarray-basedandexperiment-basedgeneexpressionanalyses.Accordingtomicroarraydata,severalgenesexhibitincreasedexpression(foldchange)buttheyareweaklyexpressedinexperimentalstudies(basedonmorphology,proteinandmRNAlevels).Incontrast,somegenesareweaklyexpressedinmicroarraydataandhighlyexpressedinexperimentalstudies;suchgenesmayrepresentfuturetargetgenesinSchwanncellstudies.Thesestudiesallowustolearnaboutadditionalgenesthatcouldbeusedtoachievetargetedresultsfromexperimentalstudies.Inthecurrentbigdatastudybyretrievingmorethan5000scientificarticlesfromPubMedorNCBI,GoogleScholar,andGoogle,1016(up-anddownregulated)genesweredeterminedtoberelatedtoSchwanncells.However,noexperimentwasperformedinthelaboratory;rather,thepresentstudyispartofabigdataanalysis.OurstudywillcontributetoourunderstandingofSchwanncellbiologybyaidingintheidentificationofgenes.Basedonacomparativeanalysisofallmicroarraydata,weconcludethatthemicroarraycouldbeagoodtoolforpredictingtheexpressionandintensityofdifferentgenesofinterestinactualexperiments.

简介：Objective:ToprovideahighlyefficientadenoviralvectorAd-CMV-hTGFβ1forthestudyofgenetherapyforreversionoftheintervertebraldiscdegeneration.Methods:Anewlydevelopedrecombinantadenoviralvectorconstructionsystemwasusedinthestudy.ThecDNAofhTGFβ1wasfirstsubclonedintoashuttleplasmidpShuttle-CMV.TheresultantplasmidwaslinearizedbydigestingwithrestrictionendonucleasePmeI,andsubsequentlytransformedintoE.coll.BJ5183cellswithanadenoviralbackboneplasmidpAdEasy-1.Recombinantswereselectedbykanamycinresistanceandconfirmedbyrestrictionendonucleaseanalysis.Finally,therecombinantplasmidlinearizedbyPmeIwastransfectedinto293cells.Recombinantadenovirusesweregeneratedwithin2weeks.Results:TherecombinantadenoviralplasmidswerecutbyBamHIandPacIrespectively,andthediagnosticfragmentsappearedin0.8%agaroseelectrophoresis.Theinfected293cellsshowedevidentcytopathlceffect(CPE).TheproductionsofPCRconfirmedthepresenceofrecombinantadenovirus.TheexpressionofhTGFβ1wasverifiedbyimmunohistochemicalstaining.Conclusions:ThesuccessfulgenerationoftheadenoviralvectorAd-CMV-hTGFβ1andtheconfirmationoftheinterestgeneexpressionmakeitpossiblefortheexperimentalstudyofthereversionoftheintervertebraldiscdegenerationbygenetherapy.

简介：为neovascular在诊断和预后调查neutrophil-to-lymphocyte比率(NLR)和platelet-to-lymphocyte比率(PLR)的地方年龄相关的有斑点的退化(AMD).METHODSOne百个AMD病人和100健康控制在学习被包括。血样品从静脉的血被获得，它被用于平淡的分析，并且这些样品被使遭到完成血计数。NLR被定义为淋巴细胞的数字划分的嗜中性的计数，并且PLR被定义为lymphocytes.RESULTSNo的数字划分的血小板计数统计上重要的差别以人口统计的特征在考虑下面在二个组之间被观察(P>0.05)。在耐心的组的平均NLR被发现在健康控制组比那显著地高(P<0.05)。平均PLR作为与控制组相比在耐心的组是显著地更高的(P<0.05)。当最好改正的视觉尖酸(BCVA)增加了，NLR和PLR减少了(在49.8%和63.0%点的重要否定关联，分别地)而当中央有斑点的厚度(CMT)增加了，NLR和PLR增加了(在59.3%和70.0%点的重要积极关联，分别地).CONCLUSIONNLR和PLR层次作为与健康控制相比在neovascularAMD病人之中是更高的组。NLR和PLR层次被发现与BCVA并且直接相反地成正比与CMT成正比。

简介：AIMTo调查经历了intravitrealranibizumabmonotherapy对待neovascular的病人的长期的视觉、解剖的结果年龄相关的有斑点的退化(AMD)并且为经历了ranibizumabmonotherapy因为neovascularAMD在这回顾的study.RESULTSThe一般水准病人年龄被包括的74个病人的74只眼睛的至少2y.METHODSA总数跟随起来是72.1

简介：Togaininsightsintotheototoxiceffectsofaminoglycosideantibiotics(AmAn)anddelayedperipheralganglionneurondeathintheinnerear.experimentalanimalmodelswerewidelyusedwithseveraldifferentapproachesincludingAmAnsystemicinjections,combinationtreatmentofAmAnanddiuretics,orlocalapplicationofAmAn.Intheseapproaches,systemicAmAntreatmentaloneusuallycausesincompletedamagetohaircellsintheinnerear.Co-administrationofdiureticandAmAncancompletelydestroythecochlearhaircells,butitisimpossibletodamagethevestibularsystem.OnlytheapproachofAmAnlocalapplicationcanselectivelyeliminatemostsensoryhaircellsintheinnerear.Therefore,AmAnlocalapplicationismoresuitableforstudiesforcompletehaircelldestructionsincochlearandvestibularsystemandthefollowingdelayedperipheralganglionneurondeath.Incurrentstudies,guineapigswereunilaterallytreatedwithahighconcentrationofgentamicin(GM,40nig/ml)throughthetympanicmembraneintothemiddleearcavity.AuditoryfunctionsandvestibularfunctionsweremeasuredbeforeandafterGMtreatment.Thelossofhaircellsanddelayeddegenerationofganglionneuronsinbothcochlearandvestibularsystemwerequantified30daysor60daysaftertreatment.TheresultsshowedthatbothauditoryandvestibularfunctionswerecompletelyabolishedafterGMtreatment.Thesensoryhaircellsweretotallymissinginthecochlea,andseverelydestroyedinvestibularend-organs.Thedelayedspiralganglionneurondeath60daysafterthedeafeningprocedurewasover50%.However,noobviouspathologicalchangeswereobservedinvestibularganglionneurons60dayspost-treatment.Theseresultsindicatedthatahighconcentrationofgentamycindeliveredtothemiddleearcavitycandestroymostsensoryhaircellsintheinnerearthatsubsequentlycausesthedelayedspiralganglionneurondegeneration.Thismodelmightbeusefulforstudiesofhaircellregenerations,delayeddegenerationofperipheralauditoryne