简介：High-gradegliomasareaggressiveanduniformlyfataltumors,composedofaheterogeneouspopulationofcellsthatincludemanywithstem-cell-likeproperties.Theacquisitionofstem-liketraitsmightcontributetogliomainitiation,growth,andrecurrence.HereweinvestigatedtheroleofthetranscriptionfactormyeloidElf-1likefactor(MEF,alsoknownasELF4)ingliomas.WefoundthatMEFishighlyexpressedinbothhumanandmouseglioblastomasanditsabsenceimpairsgliomagenesisinaPDGF-drivengliomamousemodel.WeshowthatmodulationofMEFlevelsinbothmouseneuralstemcellsandhumanglioblastomacellshasasignificantimpactonneurosphereformation.Moreover,weidentifySox2asadirectdownstreamtargetofMEF.Takentogether,ourstudiesimplicateMEFasapreviouslyunrecognizedgatekeepergeneingliomagenesisthatpromotesstemcellcharacteristicsthroughSox2activation.

简介：FromNovember1,2013,TranslationalLungCancerResearch(TLCR)isofficiallyendorsedbytheSpanishLungCancerGroup(Figure1).ThisisameaningfulmilestoneforTLCRasanacknowledgmentofitsexpansionanddedicationtolungcancerresearchandwilltremendouslyadvanceitscontinuedexplorationinthefield.SinceitwaslaunchedinMay2013,TLCRhasbeendedicatedtoprovidingcutting-edgefindingsintherapidly

简介：Chronicdiseaseshavebecomeafocalpointofpublichealthworldwidewithestimatesoftrillionsofdollarsinannualhealthcarecostandcausingmorethan36milliondeathsayear.Lifestylefactorssuchasphysicalinactivityareheavilycorrelatedwiththedevelopmentofmanychronicdiseases.Newstrategiesforprimaryandsecondarydiseasepreventionaredesperatelyneededtoaidinbluntingthenegativeeconomicandsocialimpactofthesediseases.Physicalactivity(PA)andexercisearenowconsideredprincipalinterventionsforuseinprimaryandsecondarypreventionofchronicdiseases.Currently,moreemphasisinprimarypreventionofdiseaseisnecessarytoreducediseaseriskinyouthandadults;howeverwithchronicdiseaseprevalencesohigh,similaremphasisisalsonecessaryforsecondarypreventioninthosechildrenandadultsalreadyinflictedwithchronicdiseases.Conditionssuchascardiovasculardisease,type2diabetes,obesity,andcanceraredrasticallyimprovedwhenPAandexercisearepartofamedicalmanagementplan.Inaddition,thenationalPAguidelinesinconjunctionwithPApromotiontoolslikeExerciseisMedicine?areneededtopromoteincreasedPAandexerciselevelsworldwide.

简介：Microphthalmia-associatedtranscriptionfactor(MITF)controlsmelanocytesurvivalanddifferentiationthroughdirectlyregulatingtheexpressionofthetyrosinase(TYR)andtyrosinase-relatedproteins1and2(TYRP1andTYRP2)genes.MITFmutationshavebeenreportedtoresultinanabnormalmelanocytedevel-opmentandleadtoWaardenburgsyndrometype2(WS2),characterizedbyvariabledegreesofsensorineu-ralhearinglossandpatchyregionaldistributionofhypopigmentation.Recently,MITFwasalsoindicatedasacausativegeneforamoreseveresyndrome,theTietzSyndrome(TS),characterizedbygeneralizedhy-popigmentationandcompletehearingloss.However,fewfunctionalstudieshavebeenperformedtocom-parethediseases-causingmutations.Here,weanalyzedtheinvitroactivityoftworecentidentifiedWS2-as-sociatedmutation(p.R217Iandp.T192fsX18)andoneTS-associatedmutationp.N210K.TheR217IMITFretainedpartialactivity,normalDNA-bindingabilityandnucleardistribution,whereastheT192fsX18MITFfailedtoactivateTYRpromoterduetolossofDNA-bindingactivity,andaberrantsubcellularlocalization.TheaberrantsubcellularlocalizationofT192fsX18MITFmaybecausedbydeletionofaputativenuclearlocalizationsignal(NLS)ataa213-218(ERRRRF).Indeed,MITFwithdeletionoftheNLSfragmentfailedtotranslocateintothenucleusandactivatedtheTYRpromoter.TaggingthisNLStoGFPpromotedthegreenfluorescenceprotein(GFP)translocatedintothenucleus.ThesurprisingfindingofourstudyisthataTS-as-sociatedMITFmutation,N210K,showedcomparableinvitroactivityasWT.Thus,thepossibleinvolve-mentofMITFinTSanditsunderlyingmechanismsstillneedfurtherinvestigation.

简介：AIM:ToInvestigatethegeneticfindingsandphenotypiccharacteristicsofaChinesefamilywithNorriedisease（ND）.METHODS:MoleculargeneticanalysisandclinicalexaminationswereperformedonaChinesefamilywithND.MutationsintheNorriediseasepseudoglioma（NDP）geneweredetectedbydirectsequencing.Haplotypeswereconstructedandcomparedwiththephenotypesinthefamily.Evolutionarycomparisonsandmutantopenreadingframe（ORF）predictionwerealsoundertaken.RESULTS:TwofamilymemberswithocularmanifestationswerediagnosedwithND.Nosignsofsensorineuralhearinglosswereobservedineitherpatient,whileoneofthemshowedsignsofmildmentalretardation.AnovelheterozygousmutationintheNDPgene,c.-12delAAT,wasdetectedinbothpatients.ThemutationandthemutationbearinghapiotypecosegregatedwiththeNDphenotypeinmalesandwastransmittedfromtheirmothersand/orgrandmothers（Ⅱ:2）.ThemalewithoutNDdidnotharborthemutation.Themutationoccurredatthehighlyconservednucleotides.DRFfinderpredictedthatthemutationwouldleadtotheproductionofatruncatedproteinthatlacksthefirst11N-terminalaminoacids.CONCLUSION:Anovelmutation,c.-12delAATintheNDPgene,wasidentifiedinaChinesefamilywithND.ThismutationcausedNDwithoutobvioussensorineuralhearingloss.Mentaldisorderwasfoundinonebutnottheotherpatients.Theclinicalheterogeneityinthefamilyindicatedthatothergeneticvariantsandepigeneticfactorsmayalsoplayaroleinthediseasepresentation.

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简介：Objective:Chemotherapyisthestandardtreatmentforsmall-celllungcancer(SCLC),andleukopeniaisacommonsideeffect.Thisstudyassesseswhetherchemotherapy-inducedleukopeniaisapredictorofefficacyandwhetheritisassociatedwiththesurvivalofSCLCpatients.Methods:Aretrospectiveanalysiswasconductedondatafrom445patientswithSCLCwhoreceivedstandardchemotherapyfor4to10cycles.TheWorldHealthOrganizationgradingsystemclassifiesleukopeniaduringchemotherapyasfollows:absent(grade0),mild(grades1and2),orsevere(grades3and4).Theprimaryendpointisoverallsurvival(OS).Results:Theassociationbetweenchemotherapy-inducedleukopeniaandOSwasassessed.AccordingtoamultivariateCoxmodelwithtime-varyingcovariates,thehazardratioofdeathwassignificantlyloweramongpatientswithmildleukopeniathanamongpatientswithsevereleukopeniaat0.687(0.506to0.943)and1.414(1.147to1.744),respectively.Themediansurvivalwas13months(95%CI:11to15months)forpatientswhodidnotexperienceleukopenia,17months(95%CI:14to18months)forthosewithmildleukopenia,and14months(95%CI:13to16months)forthosewithsevereleukopenia(absentvs.mildvs.severeleukopenia,P=0.047).Conclusion:LeukopeniaduringchemotherapyisassociatedwiththesurvivalofSCLCpatients.Mildleukopeniaisstronglyassociatedwithlongersurvivaltime.

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简介：A60-year-oldwomanwithsquamouscellcarcinomaintherightlungwassuccessfullytreatedwithfourcyclesofcombinationchemotherapyaftersurgery,andcompleteremissionwasachieved.However,thepatientdevelopedmyelodysplasticsyndrome(MDS)RAEB-2withmyelofibrosisafterremission,possiblybecauseofchemotherapyorDNAmethylation.Thepatientrespondedwelltodacitabine(Dacogen),suggestingthatDNAhypomethylationagentscanbeapromisingtherapytoretardtheprogressionofasecondtumororcarcinoma.

简介：SubthalamicnucleusdeepbrainstimulationhasbecomeastandardneurosurgicaltherapyforadvancedParkinson’sdisease.Subthalamicnucleusdeepbrainstimulationcandramaticallyimprovethemotorsymptomsofcarefullyselectedpatientswiththisdisease.Surprisingly,somespecificdimensionsofqualityoflife,"psychological"aspectsandsocialadjustmentdonotalwaysimprove,andtheycouldsometimesbeevenworse.Patientsandtheirfamiliesshouldfullyunderstandthatsubthalamicnucleusdeepbrainstimulationcanalterthemotorstatusandtimeisneededtoreadapttotheirnewpostoperativestateandlifestyles.Thispaperreviewstheliteraturesregardingeffectsofbilateralsubthalamicnucleusdeepbrainstimulationonsocialadjustment,qualityoflifeandcopingstrategiesinpatientswithParkinson’sdisease.ThefindingsmayhelptounderstandthepsychosocialmaladjustmentandpoorimprovementinqualityoflifeinsomeParkinson’sdiseasepatients.

简介：ThepreviousSpecialIssuewasdevotedtophysicalactivity(PA),physicalfitness,diet,andhealthinyoungpeople.ThecontentofthissecondSpecialIssuewillfocusonPAandchronicdiseaseinchildrenandyoungadults.ThefirstpaperwrittenbyDurstineetal.considerstheproblemofchronicdiseasesbecomingapublichealthconcernworldwidewithestimatesoftrillionsofdollaisinannualhealthcarecostsandcausingmorethan36milliondeathsayear.Their

简介：Metastasisoflungcancertothetemporalboneisaveryrarediseaseandsubjectivetinnitusasthepresent-ingsymptominthesepatientsisevenrarer.Herewereportacaseinwhicha42-year-oldmalepresentedwithsubjectivetinnitusofthreemonths,withnopulmonarydiseasesymptoms.Puretoneaudiometryindi-catedmoderateconductivedeafnessinleftearwithanair-bonegapof21.3dB.HRCTtemporalbonescan-ningindicatedhigh-densityshadowsintheleftepitympaniccavity,sinustympaniandmastoidcavity.Chron-icotitismediawithcholesteatomawassuspectedandsurgicaltreatmentrecommended.However,preopera-tivechestx-rayrevealedhigh-densitymilletlesionsscatteredwidelyinbothlungs.HRCTlungscanningconfirmedthelungslesionsandindicatedlungcancer.Inordertodeterminecorrelationsbetweenthetempo-ralboneandpulmonarylesions,aCT-guidedtrans-mastoidaspirationbiopsyandimmunohistochemicalstudywereconducted,whichconfirmedthatthetemporalbonelesionwasmetastaticfromthelungs.Thepa-tientwasgivenaseriesofchemotherapyimmediatelyandhistinnitussignificantlyimprovedafterthreemonthsoftreatment,withfullrecoveryofhishearingandcompleteresolutionofshadowsinthemastoidcavity.Unfortunately,hesubsequentlydevelopedmultiplebonemetastasesinthe9thmonthandcerebralmetastasisinthe18thmonth.Multipleorganfailureresultedindeathin2.5years.

简介：ObjectivesToassesswhetherstatinsreduceall-causemortalityandCVeventsinelderlypeoplewithoutestablishedCVdisease.BackgroundSinceageingofthepopulationissteadilyraising,preventionofcardiovascular(CV)diseaseintheelderlyisrelevant.InelderlypatientswithpreviousCVevents,useofstatinsisrecommendedbyguidelines,whereasbenefitsofthesedrugsinelderlysubjectswithoutpreviousCVeventsarestilldebated.MethodsRandomizedtrialscomparingstatinsversusplaceboandreportingall-causeandCVmortality,myocardialinfarction(MI),stroke,andnewcanceronsetinelderly(>65yearsold)subjectswithoutestablishedCVdiseasewereincluded.ResultsEighttrialsenrolling24,674subjects(42.7%females;meanage73.0+2.9;meanfollow-up3.5+1.5years)wereincludedinanalyses.Statins,comparedtoplacebo,significantlyreducedtheriskofMIby39.4%(relativerisk[RR]:0.606[95%confidenceinterval(CI):0.434to0.847];P=0.003),aswellastheriskofstrokeby23.8%(RR:0.762[CI:0.626to0.926];P=0.006).Incontrast,theriskofall-causedeath(RR:0.941[CI:0.856to1.035];P=0.210)andofCVdeath(RR:0.907[CI:0.686to1.199];P=0.493)werenotsignificantlyreduced.Newcanceronsetdidnotdifferbetweenstatin-comparedtoplacebotreatedsubjects(RR:0.989[CI:0.851to1.151];P=0.890).ConclusionsPInelderlysubjectsathighCVriskwithoutestablishedCVdisease,statinssignificantlyreducetheincidenceofMIandstroke,butdonotsignificantlyprolongsurvivalintheshort-term.

简介：Objective:Thisstudyinvestigatedthecapabilityofdual-energyspectralcomputedtomography(CT)toquantitativelyevaluatelungperfusiondefectsthatareinducedbycentrallungcancer.Methods:Thirty-twopatientswithcentrallungcancerunderwentCTangiographyusingspectralimaging.Aunivariategenerallinearmodelwasconductedtoanalyzethevarianceofiodineconcentration/CTvaluewiththreefactorsoflungfields.Apairedt-testwasusedtocompareiodineconcentrationsandCTvaluesbetweenthedistalendoflungcancerandthecorrespondingareainthecontralateralnormallung.Results:Iodineconcentrationsincreasedprogressivelyinthefar,intermediateandneargroundsidesinthenormallungfieldsat0.60±0.28,0.93±0.27and1.25±0.38mg/mL,respectively(P<0.001).ThesametrendwasobservedfortheCTvalues[–(840.64±49.08),–(812.66±50.85)and–(760.83±89.17)HU,P<0.001].Theiodineconcentration(0.70±0.42mg/mL)ofthelungfieldinthedistalendoflungcancerwassignificantlylowerthanthecorrespondingareainthecontralateralnormallung(1.19±0.62mg/mL)(t=–7.23,P<0.001).However,theCTvalueoflungfieldinthedistalendoflungcancerwassignificantlyhigherthanthecorrespondingareainthecontralateralnormallung[–(765.29±93.34)HUvs.–(800.07±76.18)HU,t=3.564,P=0.001].Conclusions:SpectralCTimagingbasedonthespectraldifferentiationofiodineisfeasibleandcanquantitativelyevaluatepulmonaryperfusionandidentifyperfusiondefectsthatareinducedbycentrallungcancer.SpectralCTseemstobeapromisingtechniqueforthesimultaneousevaluationofbothmorphologicalandfunctionallunginformation.

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简介：Objective:TostudythecharacteristicsofpulsetracingsinCHD,andobjectivelyevaluatethesignificanceofpulsesignalindiagnosisandappreciationoftherapeuticeffectinpatientswithcoronaryheartdisease(CHD),andaccordinglyprovidewiththeoreticproofsfordevelopingnon-invasivetechniqueofpulsediagnosis.Methods:Byusingthepulsedetectionsystem,pulsegraphsinCHDpatients,patientswithoutCHDand"health"adultswerecollectedandcompared.ThencharactersofthepulsesignalwereanalyzedwithHilbert-Huangtransformationroutine(HHT)andtime-domainmethodrespectively.Results:ThereexistedcharacteristicchangeinpulsegraphinCHD.①h1,h3,h4,h3/h1,t,t5/t4intimedomainparametersofpulsegraphincreasedandw1waswidened.②44%ofC2waveinHHTdisplayshowedchaoticanddisorderlywaveandirregularlywaveamplitudeinCHD.And72%ofC5Waveexhibitedinirregularwavewithaveragewaveamplitudeover10gram-forces.Thesechangesweresignificantlydifferentfromhealthadults.Conclusion:CharacteristicwaveofpulsegraphextractedwithmethodsoftimedomainorHHTroutinemightbeconsideredasproofsfordiagnosisanddifferentiationinCHD.OurresearchesprognosticatethatpulsediagnosiscanbeusedasanancillarydeterminationinoccurrenceofCHDforreasonsoftheadvantageofconvenientoperationandnon-invasion.

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简介：Graft-versus-host疾病(GVHD)是在造血的干细胞移植以后的最普通的复杂并发症。澄清像使用费的受体的角色4(TLR4)，它是为细菌的lipopolysaccharides(LPS)的主要受体在尖锐GVHD的发展，我们使用了一个TLR4大美人(TLR4−/−)老鼠GVHD模型并且分析了内在的免疫学的机制。当TLR4−/−老鼠被用作骨头髓和splenocyte房间接枝施主或接受者时，GVHD症状出现和死亡被推迟与相比野类型(TLR4+/+)老鼠。另外，组织病理学说的分析在TLR4−/−BALB/c怪物，肝和小肠织物损坏与最小的淋巴球的渗入被减少。与TLR4+/+,TLR4−/−老鼠相对照，树枝状的房间没在处于一个不成熟的状态感应、留下的LPS期间表示CD80，CD86，CD40，MHC-II或IL-12。而且，TLR4−/−鼠标怒气的能力支持allogeneicT房间增长的树枝状的房间和，特别地T助手房间1(Th1)开发显然与TLR4+/+鼠标相比被稀释interferon-γ的树枝状的房间，和层次；(IFN-γ；)并且IL-10，Th2房间特定的cytokines，在TLR4−/−BALB/c比在TLR4+/+BALB/c妄想的老鼠。总的来说，我们的数据表明TLR4可以在GVHD和基因治疗可能提供的那指向的TLR4的致病起一个作用减少GVHD的风险的一条新处理途径。