简介:Thesphericalheadmodelhasbeenwidelyusedinmagnetoencephalography(MEG)asasimpleforwardmodelforcalculatingtheexternalmagneticfieldproducingbyneuralcurrentsinahumanbrain.Butthismodelmayleadtoaninaccurateresult,evenifthecomputationspeedisfast.Formoreprecisecomputation,realisticbrain-shapedheadmodelisusedwiththeboundaryelementmethod(BME),butatgreatlyincreasedcomputationalcost.WhensolvingMEGinverseproblembyusingoptimizationmethods,theforwardproblemmustoftenbesolvedforthousandsofpossiblesourceconfigurations.Soifthebrain-shapedheadmodelisusedinalliterativestepsofoptimization,itmaybecomputationallyinfeasibleforpracticalapplication.Inthispaper,wepresentamethodaboutusingcompoundheadmodelinMEGinversesolution.Inthismethod,firstsphericalheadmodelisusedforaroughestimation,thenbrain-shapedheadmodelisadoptedformoreprecisesolution.Numericalsimulationindicatesthatundertheconditionofsameaccuracy,thecomputationspeedforthepresentmethodisaboutthreetimesfasterthanamethodusingthebrain-shapedheadmodelatalliterations.
简介:一个适当小动物模型的缺乏仍然是一个主要障碍因为学习immunotolerance和immunopathogenesis由肝炎B病毒(HBV)导致了感染。在这研究,我们与recombinant在感染以后与持续HBVviremia报导一个老鼠模型带一个可复制的HBV染色体(AAV/HBV)的联系adeno的病毒(AAV)。类似于临床的HBV搬运人,感染AAV/HBV的老鼠为对HBV表面抗原(HBsAg)的抗体是sero否定的。有面对铝助手疫苗的常规HBV的免疫没能在这些老鼠对HBV得到有免疫力的回答。为了识别一支疫苗,那能潜在地围绕这忍耐,TLR9收缩筋CpG作为一个助手被加到HBsAg。有HBsAg/CpG的老鼠的种痘导致了viremia,而且强壮的抗体生产和T房间回答的不仅清理。而且,DNA复制和HBV的蛋白质表示显著地在AAV/HBV-infected鼠标的肝被减少。因此,AAV/HBV-infected老鼠可以作为一个柔韧的模型被使用调查HBVimmunotolerance并且为开发新奇免疫疗法根除的内在的机制HBV感染。
简介:ObjectiveTostudytheauditionandinnerearstructureinanormalswinemodel.MethodsAuditorybrainstemresponses(ABRs)weredeterminedinswineat1dayand1monthafterbirth.Theformofthecochleaandhaircellswereexaminedunderascanningelectronmicroscopeandoncochlearslices.ResultsABRthresholdsat1dayand1monthpost-birthwerebetween40and50dBSPL.ThelatenciesofwavesI,IIIandVin1dayoldswinewere1.97±0.13,3.01±0.16and4.26±0.20ms,respectively.At1month,thelantanciesofwavesI,IIIandVwere2.01±0.05,3.11±0.08and4.65±0.14ms,respectively,slightlylongerthanthoseat1day,althoughnotstatisticallysignificant(p>0.05).Theswinecochleawasconstitutedof3andahalfturnsandthecochlearhaircellslinedupinfourrows.Haircellciliaintheapicalturnwerelongerthanthoseinotherturns.ConclusionsTheswinecochleaismatureatthetimeofbirth.SwineABRthresholdsareslightlyhigherthanhumansandrats.Swineappearstobeaprecocialanimalspecies.
简介:AbstractBackground:Traumatic brain injury, one of the leading causes of death in adults under 40 years of age in the world, is frequently caused by mechanical shock, resulting in diffuse neuronal damage and long-term cognitive dysfunction. Many existing TBI animal models revival with expensive equipment or special room are needed or the processes of operations are complex and not easy to be widely used. Therefore, a simpler TBI model needs to be designed.Methods:Our TBI model is an innovation of the modeling method through air guns shutting rubber bullets. A core facet is the application of our designed rubber bullet impact device. It could focus the hitting power to the fixed site of the brain, thus triggering a mild closed head injury. Moreover, the degree of damage can be adjusted by the times of shots.Results:Our model induced blood-brain barrier leakage and diffused neuronal damage. Besides, it led to an increased level of Tau phosphorylation and resulted in cognitive dysfunction within several weeks post-injury.Conclusion:Our TBI model is not only simple and time-saving but also can simulate mild brain injuries in clinical. It is suitable for exploring pathobiological mechanisms as well as a screening of potential therapies for TBI.
简介:BackgroundMyocardialfibrosisplaysacriticalroleintheprocessofdiabeticcardiacremolding.MicroRNAs(miRNAs)areendogenous,smallnon-codingRNAsthatnegativelyregulategeneexpressionindiversebiologicalandpathologicalprocesses.However,therolesofmiRNAsinmyocardialfibrosishavenotbeenwellelucidated.Inthepresentstudy,miRNAsprofilesinthefibroticmyocardiumofdb/dbmiceandmiRNAsexpressioninTGF-β1-stimulatedmousecardiacmyofibroblastswasexamined.MethodsHeartfunctionof18-week-olddb/dbmiceanddb/mcontrolmicewasdetectedbyechocardiography.miRNAexpressionprofileindiabeticmyocardiumwasdetectedbymiRNAmicroarray.Quantitativereal-timePCRwasusedtodeterminetheexpressionoffibrosis-relatedgenesandmiRNAprecursorsofinterest.Westernblotwasusedtodetectthelevelsoffibrosis-relatedproteins,activatedSmad3andtotalSmad3.ResultsTheresultofechocardiographyshowedthatleftventricularsystolicanddiastolicfunctionwasimpairedin18-week-olddb/dbmicewithoutsignificantchangeofejectionfraction(EF)andfractionalshortening(FS).Fibrosis-relatedgenesexpressionwasupregulatedandtheamountofphosphorylatedSmad3wasincreasedsignificantlyinthediabeticmyocardium.miRNAsdysregulationwasshownindiabeticmyocardium,sixty-eightmiRNAs,includingmiR-208b,miR-29b,miR-26bandmiR-30e,wereincreasedovertwo-fold,meanwhile,sixty-twomiRNAsweredecreasedmorethantwo-foldinthemyocardiumofdb/dbmicecomparedtodb/mcontrols.InparallelwithasignificantupregulationofCol1a1,Col3a1andCTGFmiRNAexpression,miR-208b,miR-29b,miR-26bandmiR-30eprecursorswerealsoshowntobeupregulatedinTGF-β1-inducedC57bl/6mousecardiacmyofibroblasts.ConclusionsmicroRNAsweredysregulatedindiabeticmyocardium,withtheactivationofTGF-β/smad3pathway,contributingtodiabeticmyocardialfibrosis.
简介:ObjectiveTostudyeffectsofJiangtangFanglongWan(glucose-loweringanddeafness-preventingcapsule)onhearinginananimalmodelofdiabetes.MethodsWistarratswereusedtocreateadiabetesmodelbyintraperitonealinjectionofstreptozotocin(STZ,55mg/kg).FortyratswererandomlyselectedtoreceiveJiangtangFanglongWan(10g/kg/day)throughintragastricgavage(treatmentgroup)ornormalsaline(controlgroup).Auditorybrainstemresponses(ABRs)wererecordedatMonths1,2and3.ResultsABRlatenciesandwaveintervalsweresimilarbetweenthetwogroupsatMonth1(P>0.05).ABRlatenciesandwaveintervalswereshorterinthetreatmentgroupthanthoseofthecontrolgroupatMonths2and3(P<0.05andP<0.01,respectively).ConclusionOurresultssuggestthatJiangtangFanglongWanmayhaveabeneficialeffectinpreventingandtreatinghearingimpairmentassociatedwithdiabetes.
简介:Aratmodelofchronictympanicmembraneperforationwasdevelopedtobeusedinthesearchofnewmaterialsforthesealingoftheseperforations.AlongitudinalstudywascarriedoutinratssubjectedtoincisionalmyringotomyfollowedbytheapplicationofmitomycinCaloneorwithdexamethasone.Ratswerecheckedatdays3,7,10,14andweeklythereafteruntilperforationclosure,forupto6months.Theadditionofdexamethasoneisakeycomponentinordertoobtainachronicopening.Myringotomiestreatedwithsalinehadameanhealingtimeof8.5days.At8weeks,between62.5%and77.7%oftympanicmembranestreatedwithmitomycinCanddexamethasoneremainedperforatedandat6monthsthisnumberfellto21.4%.Thistechniqueisabletomaintainmosttympanicmembraneperforationspatentforatleast8weeks.Thisratmodelisadequateforitsuseinpreclinicalortranslationalresearch.
简介:MicroRNAs(miRNAs)aredynamicallyregulatedduringneurodevelopment,yetfewreportshaveexaminedtheirroleinspinabifida.Inthisstudy,weusedanestablishedfetalratmodelofspinabifidainducedbyintragastricallyadministeringoliveoil-containingall-transretinoicacidtodamsonday10ofpregnancy.Damsthatreceivedintragastricadministrationofall-transretinoicacid-freeoliveoilservedascontrols.ThemiRNAexpressionprofileintheamnioticfluidofratsat20daysofpregnancywasanalyzedusinganmiRNAmicroarrayassay.Comparedwiththatincontrolfetuses,theexpressionofmiRNA-9,miRNA-124a,andmiRNA-138wassignificantlydecreased(>2-fold),whereastheexpressionofmiRNA-134wassignificantlyincreased(>4-fold)intheamnioticfluidofratswithfetusesmodelingspinabifida.Theseresultswerevalidatedusingreal-timequantitativereverse-transcriptionpolymerasechainreaction.HierarchicalclusteringanalysisofthemicroarraydatashowedthatthesedifferentiallyexpressedmiRNAscoulddistinguishfetusesmodelingspinabifidafromcontrolfetuses.OurbioinformaticsanalysissuggestedthatthesedifferentiallyexpressedmiRNAswereassociatedwithmanycytologicalpathways,includinganervoussystemdevelopmentsignalingpathway.ThesefindingsindicatethatfurtherstudiesarewarrantedexaminingtheroleofmiRNAsthroughtheirregulationofavarietyofcellfunctionalpathwaysinthepathogenesisofspinabifida.Suchstudiesmayprovidenoveltargetsfortheearlydiagnosisandtreatmentofspinabifida.
简介:Oxaliplatin,ananticancerdrugcommonlyusedtotreatcolorectalcancerandothertumors,hasanumberofserioussideeffects,mostnotablyneuropathyandototoxicity.Togaininsightsintoitsototoxicprofile,oxaliplatinwasappliedtoratcochlearorgancultures.Consistentwithitneurotoxicpropensity,oxaliplatinselectivelydamagednervefibersataverylowdose1μM.Incontrast,thedoserequiredtodamagehaircellsandspiralganglionneuronswas50foldhigher(50μM).Oxailiplatin-inducedcochlearlesionsinitial-lyincreasedwithdose,butunexpectedlydecreasedatveryhighdoses.Thisnon-lineardoseresponsecouldberelatedtodepressedoxaliplatinuptakeviaactivetransportmechanisms.Previousstudieshavedemon-stratedthataxonaldegenerationinvolvesbiologicallyactiveprocesseswhichcanbegreatlyattenuatedbynicotinamideadeninedinucleotide(NAD+).TodetermineifNAD+wouldprotectspiralganglionaxonsandthehaircellsfromoxaliplatindamage,cochlearculturesweretreatedwithoxaliplatinaloneatdosesof10μMor50μMrespectivelyascontrolsorcombinedwith20mMNAD+.Treatmentwith10μMoxaliplatinfor48hoursresultedinminordamagetoauditorynervefibers,butsparedcochlearhaircells.However,whencochlearculturesweretreatedwith10μMoxaliplatinplus20mMNAD+,mostauditorynervefiberswereintact.50μMoxaliplatindestroyedmostofspiralganglionneuronsandcochlearhaircellswithapop-toticcharacteristicsofcellfragmentations.However,50μMoxaliplatinplus20mMNAD+treatmentgreat-lyreducedneuronaldegenerationsandhaircellmissing.TheresultssuggestedthatNAD+providessignifi-cantprotectionagainstoxaliplatin-inducedneurotoxicityandototoxicity,whichmaybeduetoitsactionsofantioxidant,antiapoptosis,andenergysupply.
简介:
简介:Objective:Theaimofthepresentstudywastoconstructariskassessmentmodelwhichwastestedbydisease-freesurvival(DFS)ofesophagealcancerafterradicalsurgery.Methods:Atotalof164consecutiveesophagealcancerpatientswhohadundergoneradicalsurgerybetweenJanuary2005andDecember2006wereretrospectivelyanalyzed.Thecutpointofvalueatrisk(VaR)wasinferredbystem-and-leafplot,aswellasbyindependent-samplest-testforrecurrence-freetime,furtherconfirmedbycrosstabchi-squaretest,univariateanalysisandCoxregressionanalysisforDFS.Results:ThecutpointofVaRwas0.3onthebasisofourmodel.Therateofrecurrencewas30.3%(30/99)and52.3%(34/65)inVaR<0.3andVaR≥0.3(chi-squaretest,χ2=7.984,P=0.005),respectively.The1-,3-,and5-yearDFSofesophagealcancerafterradicalsurgerywas70.4%,48.7%,and45.3%,respectivelyinVaR≥0.3,whereas91.5%,75.8%,and67.3%,respectivelyinVaR<0.3(Log-ranktest,χ2=9.59,P=0.0020),andfurtherconfirmedbyCoxregressionanalysis[hazardratio=2.10,95%confidenceinterval(CI):1.2649-3.4751;P=0.0041].Conclusions:Themodelcouldbeappliedforintegratedassessmentofrecurrenceriskafterradicalsurgeryforesophagealcancer.
简介:瞄准:估计probioticBifidobacteriumlactis的反煽动性的效果(B。lactis)在大肠炎的一个采纳转移模型。方法:施主和接受者老鼠收到了任何一个B。lactis或象在在天真、规章的T房间的混合的转移以前喝水一个星期直到牺牲的控制(deManRogosaSharpe)中等的细菌的文化。结果:所有接受者老鼠开发了结肠的发炎的符号,但是重量损失的重要减小在B被观察。与控制鼠标相比的喂lactis的接受者鼠标。而且,向mucosal厚度和稀释上皮的损坏的减少的一个趋势被揭示。支持inflammatory和T房间标记的结肠的表示显著地在B被减少。与控制相比的喂lactis的接受者老鼠。附随地,forkhead盒子蛋白质3,规章的T房间的一个标记,由B是显著地起来调整的。lactis。结论:B的每天口头的管理。lactis对煽动性的还原剂和T房间调停人有能力,在一只老鼠的特定的标记大肠炎当模特儿支持规章的T房间。
简介:客观:在vitro建立Sprague-Dawley老鼠的海马趾的神经原的一个简单、可再现、实际的机械损害模型。方法;从1-2-day孤立的海马趾的神经原年老的老鼠在vitro是有教养的。温和、中等、严重的机械损害被分别地撕的注射针送到神经原。控制神经原与损伤的例外相等被对待。房间损坏被在损害以后测量在不同时间的碘化物(PI)uptaking削尖的thePropidium(0.5,1,6,12和24个小时)估计。特定的enolase也是的神经原的集中在一些时间测量了点。结果;病理学的检查证明那退化,降级和坏死在受伤有教养的神经原发生了。与控制组相比,在受伤的组的Pi积极的房间的比率在30分钟损害以后显著地增加了(P<0.05)。更严重损坏是,更PI积极的神经原被检测。与控制组相比,在受伤文化的特定的enolase在1小时损害以后显著地增加了的神经原的集中(P<0.05)。结论:在vitro的海马趾的神经原损害的确定的模型能容易被重复并且能模仿创伤的大脑损害的损坏机制,它能在创伤的大脑损害的未来研究被使用。
简介:Objective:Toestablishananimalmodeloflike-auditoryneuropathyinneonatalrat.MethodsTheani-malswereinjectedwithphenylhydrazinehydrochlorideorsalineat7-dayofage.ABRandDPOAEwereperformedtoassesstheauditoryfunction.Thecochleabasilarmembranestretchedpreparationandcochlearfrozensectionswerepreparedforimmunohistochemicalstainingtoexaminethemorphologicalchangeofhaircellsandspiralganglioncells(SGNs).ResultsAt7-dayagetheABRwaveI,III,V,latenciesandI-III,I-VIWIsintheexperimentalgroupweresignificantlyprolongedcomparedwiththoseinthecontrolgroup.TheABRthresholdswerealsoelevatedintheexperimentalgroup.Wefoundthereisnosignificantdiffer-enceinDPOAEinphenylhydrazinehydrochlorideexposuregroupcomparetocontrolgroup.Thecochlearhaircellsshowednosignsoflossinbothgroup,butthetotalnumberofneurofilamentspositivecellsinSGNsweresignificantlyreducedinthephenylhydrazinetreatedanimals.ConclusionOurstudysuggeststhatphenylhydrazinehydrochloridecanchangetheauditoryfunctionandinduceperipheralnervepathologybytargetedmainlytheSGNsinneonatalrat.
简介:Objective:Toestablishagoodrecoverableratmodelofcardiopulmonarybypass(CPB)tolaythefoundationforstudyingthepathophysiologyofCPB.Methods:TwentyadultmaleSprague-Dawleyratsweighing480g±20gwererandomlydividedintoCPBgroup(n=10)andShamgroup(n=10).Allratswereanaesthetized,intubatedandventilated.Thecarotidarteryandjugularveinwerecannulated.Thebloodwasdrainedfromtherightatriumviatherightjugularveinandfurthertransferredbyaminiaturizedrollerpumptoahollowfiberoxgenatorandbacktotheratviatheleftcarotidartery.Primingconsistedof8mlofhomologousbloodand6mlofcolloid.Thesurfaceofthehollowfiberoxgenatorwas0.075m~2.Ratswerecatheterizedandbroughtinbypassfor120minataflowrateof100-120ml/kg/min.Oxygenflow/perfusionflowwas0.8to1.0,themeanarterialpressure(MAP)keptin60-80mmHg.Bloodgasanalysis,lactatedehydrogenase(LDH),andsurvivalratewereexaminedsubsequently.Resnits:AllCPBratsrecoveredfromtheoperativeprocesswithoutincidentandremaineduneventfulwithinoneweek.Normalcardiacfunctionaftersuccessfulweaningwasconfirmedbyelectrocardiographyandbloodpressuremeasurements.MAPremainedstable.Theresultsofbloodgasanalysisatdifferenttimepointswerewithinanormalrange.NosignificanthaemolysiscouldbedetectedinthegiventimeframeunderbypassconditionbyusingLDH.Conclusions:TheratmodelofCPBcanprincipallysimulatetheclinicalsettingofhumanCPB.Thenon-transthoracicmodeliseasytoestablishandisassociatedwithexcellentrecovery.ThiswellreproduciblemodelmayopenthefieldforvariousstudiesonpathophysiologicalprocessofCPBandalsoofsystemicischemia-reperfusioninjuryinvivo.