簡(jiǎn)介：RADIOLOGYORIGINALARTICLEVALUEOFAPPARENTDIFFUSIONCOEFFICIENTMEASUREMENTFORDISCRIMINATIONOFFOCALBENIGNANDMALIGNANTHEPATICMASSESOKILICKESMEZ,1SBAYRAMOGLU,2EINCI2ANDTCIMILLI21DEPARTMENTOFRADIOLOGY,SCHOOLOFMEDICINE,YEDITEPEUNIVERSITYAND2DEPARTMENTOFRADIOLOGY,ISTANBULBAKIRKOYDRSADIKONUKTRAININGANDRESEARCHHOSPITAL,ISTANBUL,TURKEYOKILICKESMEZMDSBAYRAMOGLUMDEINCIMDTCIMILLIMDCORRESPONDENCEDROZGURKILICKESMEZ,DEPARTMENTOFRADIOLOGY,SCHOOLOFMEDICINE,YEDITEPEUNIVERSITY,DEVLETYOLUANKARASTREET102/104,KOZYATAGI34752,ISTANBUL,TURKEYEMAILOKILICKESMEZYAHOOCOMCONFLICTSOFINTERESTNONESUBMITTED30JULY2008ACCEPTED31JULY2008DOI101111/J17549485200902036XSUMMARYTHEPURPOSEOFOURSTUDYWASTOINVESTIGATETHEVALUEOFDIFFUSIONWEIGHTEDMAGNETICRESONANCEIMAGINGDWMRITODISCRIMINATEBENIGNANDMALIGNANTFOCALLESIONSOFTHELIVERUSINGPARALLELIMAGINGTECHNIQUEATOTALOF77PATIENTSAND65HEALTHYCONTROLSWEREENROLLEDINTHESTUDYDWMRIWASPERFORMEDWITHBFACTORSOF0,500AND1000S/MM2,ANDTHEAPPARENTDIFFUSIONCOEFFICIENTSADCVALUESOFTHENORMALLIVERANDTHELESIONSWERECALCULATEDTHEMEANADCVALUEOFTHEFOCALLIVERLESIONSWEREASFOLLOWSSIMPLECYSTS316±018?1023MM2/S,HYDATIDCYSTS258±053?1023MM2/S,HEMANGIOMAS197±049?1023MM2/S,METASTASES114±041?1023MM2/SANDHEPATOCELLULARCARCINOMASHCC115±036?1023MM2/STHEMEANADCVALUESOFALLTHEDISEASEGROUPSWERESTATISTICALLYSIGNIFICANTWHENCOMPAREDWITHTHEMEANADCVALUEOFTHENORMALLIVER156±014?1023MM2/S,P001THEREWEREALSOSTATISTICALLYSIGNIFICANTDIFFERENCESAMONGTHEADCVALUESOFHEMANGIOMASANDHCCMETASTASESP001,ANDSIMPLEANDHYDATIDCYSTSP0008HOWEVER,THEREWASNOSTATISTICALLYSIGNIFICANTDIFFERENCEBETWEENHCCANDMETASTASESTHEPRESENTSTUDYSHOWEDTHATADCMEASUREMENTHASTHEPOTENTIALTODIFFERENTIATEBENIGNANDMALIGNANTFOCALHEPATICLESIONSWEPROPOSETOADDDWSEQUENCEINTHEMRPROTOCOLFORTHEDETECTIONANDQUANTITATIVEDISCRIMINATIONOFHEPATICPATHOLOGIESKEYWORDSABDOMENDIFFUSIONWEIGHTEDIMAGINGLIVERMAGNETICRESONANCEIMAGINGINTRODUCTIONMAGNETICRESONANCEIMAGINGISCONSIDEREDTHEMOSTACCURATEMODALITYTOIMAGETHELIVERFORDETECTIONANDCHARACTERIZATIONOFDIFFUSEANDFOCALLIVERDISEASESANDTODISCRIMINATEBENIGNFROMMALIGNANTTUMORS,REFLECTINGITSABILITYONTHEBASISOFVARIOUSDATAACQUIRED,SUCHAST1,T2,ANDEARLYANDLATEPOSTGADOLINIUMIMAGES1,2CHARACTERIZATIONOFFOCALLIVERLESIONSISVERYIMPORTANTBECAUSEPATIENTSWITHKNOWNPRIMARYMALIGNANTNEOPLASMSOFTENHAVEBENIGNFOCALLIVERLESIONS,WHICHMUSTBEDIFFERENTIATEDFROMMETASTASESTHELACKOFIONIZINGRADIATIONWITHMRIMAGINGANDTHESAFETYOFGADOLINIUMCHELATES,ASCOMPAREDWITHIODINATEDCONTRASTAGENTS,ARETWOIMPORTANTCONSIDERATIONSFORTHEPREFERENTIALUSEOFMRIMAGINGOVERCTSCANNINGINTHEINVESTIGATIONOFLIVERDISEASE3FURTHERMORE,DWIHASEMERGEDASANEWDIAGNOSTICTOOLWITHTHEABILITYTODETECTFOCALLESIONSANDTODISCRIMINATEMALIGNANTONESWITHOUTTHENEEDFORCONTRASTMATERIAL4–7WEAIMEDTOINVESTIGATEWHETHERDWIHASTHEABILITYTODETECTMALIGNANCYANDTODISCRIMINATEMETASTASESANDHEPATOCELLULARCARCINOMASMETHODSTHISWASARETROSPECTIVESTUDYCONDUCTEDATOURINSTITUTIONBETWEENJANUARY2006ANDMARCH2007ATOTALOF77PATIENTS42WOMEN,35MENMEANAGE,59YEARSAND65HEALTHYCONTROLS35WOMEN,30MENMEANAGE,35YEARSWITHCOMPLETELYNORMALLIVERMRIANDLABORATORYFINDINGSWEREENROLLEDINTHESTUDYTHERESEARCHPROTOCOLWASAPPROVEDBYTHEETHICSCOMMITTEEOFOURINSTITUTIONWRITTENCONSENTWASOBTAINEDFROMALLPATIENTSPRIORTOCOMMENCEMENTOFTHESTUDYMAGNETICRESONANCEIMAGINGWASPERFORMEDONA1,5TBODYSCANNERAVANTOSIEMENS,ERLANGEN,GERMANYJOURNALOFMEDICALIMAGINGANDRADIATIONONCOLOGY53200950–5550a2009THEAUTHORSJOURNALCOMPILATIONa2009THEROYALAUSTRALIANANDNEWZEALANDCOLLEGEOFRADIOLOGISTSCLOSESTTHREEMEASUREMENTSINTHEPATIENTGROUP,AFREEHANDROIWASDEFINEDFORTHELESIONSDETECTEDONTHET2WEIGHTEDEPIIMAGEB0,WHILEREFERRINGTOTHECONVENTIONALSEQUENCESFORVERIFICATIONOFTHELESIONBOUNDARIESTHEROIWASTHENCOPIEDTOTHECORRESPONDINGADCMAPSTATISTICALANALYSISALLSTATISTICALANALYSESWEREPERFORMEDUSINGSPSSSTATISTICALPACKAGEFORSOCIALSCIENCESFORWINDOWS100THEADCVALUESOFCASESAREREPORTEDASTHEMEAN±STANDARDDEVIATIONVARIANCEANALYSISANDPAIREDSAMPLESTESTWEREALSOCONDUCTEDFORCOMPARISONOFSEGMENTSOFABDOMINALORGANSAPVALUEOFLESSTHAN005WASCONSIDEREDTOINDICATEASTATISTICALLYSIGNIFICANTDIFFERENCERESULTSAPPARENTDIFFUSIONCOEFFICIENTVALUESOFALLTHEPATIENTSWHOUNDERWENTCONVENTIONALANDDIFFUSIONWEIGHTEDMREXAMINATIONSARELISTEDASBOXPLOTSINFIGURE1THEMEANADCVALUEOFTHELIVERLESIONSWEREASFOLLOWSTABLE1SIMPLECYSTS,20CASES316±018?1023MM2/SHYDATIDCYSTS,13CASES258±053?1023MM2/SHEMANGIOMAS,15CASES197±049?1023MM2/SMETASTASES,13CASES114±041?1023MM2/SANDHEPATOCELLULARCARCINOMASHCC13CASES115±036?1023MM2/STHEMEANADCVALUESOFALLOFTHEDISEASEGROUPSWERESTATISTICALLYSIGNIFICANTWHENCOMPAREDWITHMEANADCVALUEOFTHENORMALLIVERGROUP156±014?1023MM2/S,P001THEREWEREALSOSTATISTICALLYSIGNIFICANTDIFFERENCESAMONGTHEADCVALUESOFHEMANGIOMASANDHCCMETASTASESP001,ANDSIMPLEANDHYDATIDCYSTSP0008HOWEVER,THEREWASNOSTATISTICALLYSIGNIFICANTDIFFERENCEBETWEENHCCANDMETASTASESREPRESENTATIVECASESARESHOWNINFIGURES2–5DISCUSSIONDIFFUSIONISTHETERMUSEDTODESCRIBETHERANDOMBROWNIANMOTIONOFWATERMOLECULES8WITHAVERYSTRONGBIPOLARGRADIENTPULSEINSERTEDINTOEITHERASPINECHOPULSESEQUENCEIESTEJSKALTANNERTECHNIQUEORAGRADIENTECHOPULSESEQUENCE,MRIMAGINGCANBEMADESENSITIVETOTHEDIFFUSIONOFWATERMOLECULESINTHETISSUE6,9DIFFUSIONRESTRICTIONINCREASESINHIGHLYCELLULARTISSUESINCONTRAST,ITDECREASESINLOWCELLULARTISSUESWITHLARGEEXTRACELLULARSPACEORWITHBROKENDOWNCELLULARMEMBRANES7STUDIESHAVEBEENPUBLISHEDCONCERNINGTHEDIFFUSIONPROPERTIESOFFOCALHEPATICLESIONSMOSTOFTHESTUDIESREVEALEDTHATADCVALUESOFBENIGNLESIONSCYSTSANDHEMANGIOMASWERESIGNIFICANTLYHIGHERTHANTHOSEOFMALIGNANTLESIONSATTRIBUTEDTOHIGHCELLULARITYOFMALIGNANTMASSES10–12ASWITHTHEPREVIOUSSTUDIES,WEFOUNDTHATHEPATICCYSTSHADTHEHIGHESTADCBECAUSEOFTHEIRFLUIDCONTENT,WITHNONRESTRICTEDMOTIONOFWATERMOLECULES4,10TABLE1ADCVALUESOFTHEFOCALLIVERLESIONSLESIONSNMEANADCMM2/SNORMALLIVER65156±014?1023MM2/SSIMPLECYSTS20316±018?1023MM2/SHYDATIDCYSTS13258±053?1023MM2/SHEMANGIOMAS15197±049?1023MM2/SHEPATOCELLULARCARCINOMAS13115±036?1023MM2/SMETASTASES13114±041?1023MM2/SADC,APPARENTDIFFUSIONCOEFFICIENTSFIG2FORTYYEAROLDWOMANWITHHEMANGIOMAAAXIALFST2WIMAGEREVEALSAMARKEDHYPERINTENSELESIONBAXIALDIFFUSIONWEIGHTEDB1000S/MM2IMAGEREVEALSMODERATEHYPERINTENSITYCAPPARENTDIFFUSIONCOEFFICIENTSADCWERECALCULATEDTUMORONADCIMAGESHOWSMILDHYPERINTENSITYSLIGHTLYINCREASEDDIFFUSIONCOMPAREDWITHNORMALPARENCHYMAREGIONOFINTERESTWASPLACEDONMASSROI1,CADCOFLESIONWAS192?1023MM2/SOKILICKESMEZETAL52a2009THEAUTHORSJOURNALCOMPILATIONa2009THEROYALAUSTRALIANANDNEWZEALANDCOLLEGEOFRADIOLOGISTS

簡(jiǎn)介：MAGE,BAGE,ANDGAGEGENEEXPRESSIONINPATIENTSWITHESOPHAGEALSQUAMOUSCELLCARCINOMAANDADENOCARCINOMAOFTHEGASTRICCARDIAANNALISAZAMBON,PHD1SUSANNAMANDRUZZATO,PHD1ANNAPARENTI,MD2BEATRICEMACINO,PHD1PIERODALERBA,MD1ALBERTORUOL,MD3STEFANOMERIGLIANO,MD3GIOVANNIZANINOTTO,MD3PAOLAZANOVELLO,PHD11DEPARTMENTOFONCOLOGYANDSURGICALSCIENCES,ONCOLOGYSECTION,UNIVERSITYOFPADOVA,PADOVA,ITALY2DEPARTMENTOFONCOLOGYANDSURGICALSCIENCES,PATHOLOGYSECTION,UNIVERSITYOFPADOVA,PADOVA,ITALY3DEPARTMENTOFMEDICALANDSURGICALSCIENCES,CLINICACHIRURGICA4,UNIVERSITYOFPADOVA,PADOVA,ITALYPRESENTEDATTHE33RDCONGRESSOFTHEEUROPEANSOCIETYFORSURGICALRESEARCHESSR,PADOVA,ITALY,APRIL22–25,1998ANDATTHEINTERNATIONALSOCIETYFORTHEDISEASESOFTHEESOPHAGUSISDESEVENTHWORLDCONGRESS,MONTREAL,QUEBEC,CANADA,SEPTEMBER1–41998SUPPORTEDBYTHEASSOCIAZIONEITALIANAPERLARICERCASULCANCROAIRC,MILAN,ITALYANDTHEREGIONEVENETOGRANT657/02/96,RICERCASANITARIAFINALIZZATASMWASSUPPORTEDBYAPOSTDOCTORALFELLOWSHIPFROMICGEB,TRIESTE,ITALYANDBMWASSUPPORTEDBYAPERSONALGRANTFROMAIRCTHEAUTHORSAREGRATEFULTODRGLDESALVOANDMEPIFANIFORSTATISTICALANALYSISANDTOPSEGATOFORHELPINARTICLEPREPARATIONADDRESSFORREPRINTSALBERTORUOL,MD,CLINICACHIRURGICA4,UNIVERSITYOFPADOVA,VIAGIUSTINIANI,2,35128PADOVA,ITALYFAX?390498213152EMAILARUOLUX1UNIPDITRECEIVEDJUNE28,2000REVISIONRECEIVEDJANUARY10,2001ACCEPTEDJANUARY19,2001BACKGROUNDTHEMAGE,BAGE,ANDGAGEGENEFAMILIESCODEFORDISTINCT,TUMORSPECIFICANTIGENSTHATARERECOGNIZEDBYCYTOTOXICTLYMPHOCYTESINTHECONTEXTOFHLAMOLECULESTHEPURPOSEOFTHISSTUDYWASTOANALYZEMAGE,BAGE,ANDGAGEGENEEXPRESSIONINTHETWOMAJORHISTOLOGICTYPESOFESOPHAGEALCARCINOMA,SQUAMOUSCARCINOMAESCCANDADENOCARCINOMACAC,ANDTOCORRELATETHEIREXPRESSIONPATTERNSWITHTHEPRINCIPALPROGNOSTICPARAMETERSANDLONGTERMSURVIVALMETHODSGENEEXPRESSIONWASANALYZEDINSURGICALSAMPLESFROM24PATIENTSWITHESCCAND24PATIENTSWITHCACBYREVERSETRANSCRIPTASEPOLYMERASECHAINREACTIONAMPLIFICATIONRTPCRNONEOFTHEPATIENTSHADRECEIVEDPREOPERATIVECHEMOTHERAPYORRADIOTHERAPY,ANDALLWEREFOLLOWEDUNTILDEATHORFORAMINIMUMOF4YEARSRESULTSSIXTEENESCCSAMPLES67AND9CACSAMPLES375EXPRESSEDATLEASTONEOFTHEGENESUNDERSTUDYTHEEXPRESSIONOFEACHMAGEGENEINTHETWOHISTOLOGICTYPESWASNOTSIGNIFICANTLYDIFFERENT,WITHTHEEXCEPTIONOFMAGE4,WHICHWASEXPRESSEDMOREINESCCSAMPLESTHANINCACSAMPLESBAGEANDGAGEEXPRESSIONWASRATHERLOWAND,INEVERYCASE,WASASSOCIATEDWITHTHEEXPRESSIONOFATLEASTONEMAGEGENECONCLUSIONSINTHEGROUPASAWHOLE,ANDINBOTHESCCANDCACSUBGROUPS,NOSIGNIFICANTCORRELATIONEMERGEDBETWEENTHEEXPRESSIONOFANYGENEANDPROGNOSTICPARAMETERS,SUCHASPATHOLOGICTUMOR,LYMPHNODE,ORDISEASESTAGENEVERTHELESS,BAGEORGAGEEXPRESSIONWASRELATEDSIGNIFICANTLYTOAPOORPROGNOSIS,WHEREASTHEEXPRESSIONOFMAGEGENESINTHEABSENCEOFBAGEANDGAGEEXPRESSIONWASRELATEDSIGNIFICANTLYTOAGOODPROGNOSISCANCER2001911882–8?2001AMERICANCANCERSOCIETYKEYWORDSESOPHAGEALCARCINOMA,TUMORANTIGENS,MAGE,BAGE,GAGEINRECENTYEARS,NUMEROUSHUMANTUMORANTIGENSTHATARERECOGNIZEDBYAUTOLOGOUSCYTOTOXICTLYMPHOCYTESCTLSHAVEBEENIDENTIFIED1ANIMPORTANTCATEGORYOFTHESESOCALLEDTCELLDEFINEDTUMORANTIGENSCONSISTSOFNORMALGENEPRODUCTSTHATARENOTEXPRESSEDINMOSTBODYTISSUES,WITHTHEEXCEPTIONOFMALEGERMLINECELLSANDPLACENTA,ANDAREACTIVATEDINANUMBEROFDIFFERENTTUMORSANTIGENICPEPTIDESENCODEDBYTHEMAGE,BAGE,ANDGAGEGENEFAMILIESAREPROTOTYPESOFTHISCATEGORYOFSHAREDTUMORANTIGENS2–5ALTHOUGHTHEYINITIALLYWEREDESCRIBEDINMELANOMA,THESEGENESHAVEBEENFOUNDTOBEEXPRESSEDINASUBSTANTIALNUMBEROFSOLIDTUMORSINVARIOUSORGANS,SUCHASLUNG,BREAST,BLADDER,HEADANDNECK,ESOPHAGUS,ANDSTOMACH,ASWELLASINSEVERALTUMORCELLLINES2BECAUSEOFTHEIRSTRICTTUMORSPECIFICITY,THEYAREOFPARTICULARINTERESTFORCANCERIMMUNOTHERAPY1882?2001AMERICANCANCERSOCIETYDEOXYNUCLEOTIDESDNTPS,1?LOFA500?G/MLSOLUTIONOFOLIGODT12–18PRIMERS,20UNITSOFRNASEOUTGIBCOBRL,2?LOF01M1,4DITHIOTHREITOL,AND200UNITSOFMOLONEYMURINELEUKEMIAVIRUSREVERSETRANSCRIPTASEGIBCOBRLTHEREACTIONWASINCUBATEDAT42°CFOR60MINUTESANDTHENDILUTEDTO40?LWITHWATERTWOMICROLITERSOFTHECDNAMIXTUREWEREUSEDFOREACHPOLYMERASECHAINREACTIONPCRAMPLIFICATIONINA50?LREACTIONVOLUMECONTAINING1?LOFEACHPRIMER40?M,1?LEACHOF25MMDNTP,15MMMGCL2,AND2UNITSTAQDNAPOLYMERASEPROMEGA,MADISON,WIINBUFFERA,WHICHWASSUPPLIEDBYTHEMANUFACTURERTHEPRIMERSUSEDINTHISSTUDYTOENSURESPECIFICITYFOREACHGENEWEREDESCRIBEDPREVIOUSLY3,4,9THIRTYTWOAMPLIFICATIONCYCLESWERERUN1MINUTEAT94°CAND3MINUTESAT72°CFORMAGE1ANDMAGE31MINUTEAT94°C,2MINUTESAT68°C,AND2MINUTESAT72°CFORMAGE2ANDMAGE41MINUTEAT94°C,2MINUTESAT70°C,AND2MINUTESAT72°CFORMAGE61MINUTEAT94°C,2MINUTESAT62°C,AND2MINUTESAT73°CFORBAGEAND1MINUTEAT94°C,2MINUTESAT55°C,AND2MINUTESAT72°CFORALLOFTHEGAGEGENESCYCLINGWASCONCLUDEDWITHAFINALEXTENSIONSTEPOF15MINUTESAT72°CTOVERIFYRNAINTEGRITYINEACHSAMPLE,23CYCLESFOR1MINUTEAT94°C,2MINUTESAT68°C,AND2MINUTESAT72°CWERERUNWITHPRIMERSSPECIFICFOR?ACTINAFTERAMPLIFICATION,PCRPRODUCTSWEREANALYZEDBYAGAROSEGELELECTROPHORESISSTATISTICALANALYSISSTATISTICALANALYSESWEREPERFORMEDUSINGTHESASSTATISTICALPACKAGESAS,INC,CARY,NCDIFFERENCESBETWEENGROUPSWEREASSESSEDBYCHISQUAREANALYSIS,FISHEREXACTTEST,ORSTUDENTTTEST,ASINDICATEDALLPVALUES?005WERECONSIDEREDSIGNIFICANTSURVIVALWASMEASUREDFROMTHEDATEOFSURGERYTODEATHORLASTDATEOFFOLLOWUPSURVIVALRATESANDSTANDARDERRORSWERECALCULATEDBYTHEKAPLAN–MEIERMETHOD,INCLUDINGDEATHSFROMALLCAUSES,EXCEPTTHETWOHOSPITALDEATHSTHATWERERELATEDTOPOSTOPERATIVECOMPLICATIONSTHESTATISTICALSIGNIFICANCEOFDIFFERENCESINSURVIVALWASANALYZEDBYTHELOGRANKTEST,WITHP?005CONSIDEREDSIGNIFICANTTHEPROGNOSTICIMPORTANCEOFCLINICALVARIABLESWASEVALUATEDBYACOXPROPORTIONALHAZARDREGRESSIONUSINGMULTIVARIATEANALYSISRESULTSMAGE1,MAGE2,MAGE3,MAGE4,MAGE6,BAGE,ANDGAGEGENEEXPRESSIONWASEVALUATEDIN48SURGICALSPECIMENS,OFWHICH24SPECIMENSWEREESCC,AND24SPECIMENSWERECACTABLE1,ANDIN5SAMPLESOFNORMALESOPHAGEALTISSUEADJACENTTOTHETUMORSIXTYSEVENPERCENTOFTHEESCCTUMORSAND375OFTHECACTUMORSEXPRESSEDATLEASTONEOFTHESEGENESFIGURE1SHOWSTHEDIFFERENTPATTERNSOFMAGEBAGEGAGEGENEEXPRESSIONINEIGHTREPRESENTATIVECACSAMPLESTOGETHERWITHAPPROPRIATECONTROLSTABLE2SHOWSTHATTHEPATTERNOFMAGEGENEEXPRESSIONWASVERYSIMILARINBOTHESCCANDCACSAMPLES,EXCEPTFORMAGE4,WHICHWASEXPRESSEDSIGNIFICANTLYMOREINTHEESCCSAMPLES58VS25,RESPECTIVELYP?0019TWOESCCSAMPLES8,BUTNONEOFTHECACSAMPLES,EXPRESSEDBAGEP?0149GAGEGENEEXPRESSIONWASOBSERVEDINFOURESCCSAMPLES17ANDINTHREECACSAMPLES13P?0683NONEOFTHEGENESUNDERSTUDYWASEXPRESSEDINNORMALESOPHAGEALTISSUESAMPLESDATANOTSHOWNWEINVESTIGATEDTHEASSOCIATIONBETWEENMAGE,BAGE,ANDGAGEGENEEXPRESSION,ANDTHECLINICOPATHOLOGICPARAMETERSLISTEDINTABLE1INTHEGROUPOFPATIENTSASAWHOLEANDINBOTHESCCANDCACSUBGROUPS,NOSIGNIFICANTCORRELATIONEMERGEDBETWEENTHEEXPRESSIONOFANYOFTHESEGENES,ANDPATIENTGENDERANDAGE,HISTOLOGICTUMORTYPEANDGRADINGPT,PN,ANDPSTAGE,ANDTYPEOFRESECTION,WITHTHESINGLEEXCEPTIONOFTHEGAGEGENE,WHICHWASEXPRESSEDSIGNIFICANTLYMOREINTUMORSAMPLESOBTAINEDFROMPATIENTSWHOUNDERWENTR1–R2RESECTIONP?0027DATANOTSHOWNMAGE,BAGE,ANDGAGEGENEEXPRESSIONAPPEAREDTOBECLUSTEREDINASUBSETOFTHETUMORSEXAMINED,BECAUSEMOSTLESIONSEITHERDIDNOTEXPRESSANYGENE4823OF48PATIENTSORSIMULTANEOUSLYCOEXPRESSEDTHREEORMOREGENES3517OF48PATIENTSTABLE3BAGEANDGAGEGENESALWAYSWERECOEXPRESSEDWITHONEORMOREMEMBERSOFTHEMAGEFAMILYTHEOVERALL1YEAR,3YEAR,AND5YEARACTUARIALSURVIVALRATESOFPATIENTSSURVIVINGESOPHAGECTOMYN?46PATIENTSWERE85,41,AND24,RESPECTIVELYTHE1YEAR,3YEAR,AND5YEARACTUARIALSURVIVALRATESAFTERR0RESECTIONN?37PATIENTSWERE89,51,AND30,RESPECTIVELYTABLE4SUMMARIZESTHEUNIVARIATEANALYSISOFTHEPROGNOSTICVALUEOFSEVERALCLINICOPATHOLOGICPARAMETERSINTHEFIRSTSETOFSURVIVALANALYSES,THESAMPLESWEREDIVIDEDINTOTWOCOHORTSTHOSEEXPRESSINGONEORMOREOFTHEGENESSTUDIEDANDTHOSESHOWINGNOGENEEXPRESSIONINTHEENTIREGROUPOFPATIENTSANDINBOTHESCCANDCACSUBGROUPS,WHICHWEREEVALUATEDSEPARATELY,NOSIGNIFICANTASSOCIATIONWASFOUNDBETWEENTHEABOVETWOCOHORTSANDSURVIVALDATANOTSHOWNASIMILARANALYSISWASCARRIEDOUTFOREACHOFTHEMAGE,BAGE,ANDGAGEGENESSEPARATELYONLYBAGEORGAGEEXPRESSIONWASRELATEDSIGNIFICANTLYTOAPOORPROGNOSISTABLE4FINALLY,WEGROUPEDTHEPATIENTSACCORDINGTOTHE1884CANCERMAY15,2001/VOLUME91/NUMBER10

簡(jiǎn)介：中文中文3650字，字，2660單詞，單詞，14000英文字符英文字符出處出處TORRICELLIFCM,DES,SARKISSIANC,ETALHYDROPHILICGUIDEWIRESEVALUATIONANDCOMPARISONOFTHEIRPROPERTIESANDSAFETYJUROLOGY,2013,82511821186親水導(dǎo)絲親水導(dǎo)絲評(píng)估和比較其性能與安全性評(píng)估和比較其性能與安全性FABIOCESARMIRANDATORRICELLI，SHUBHADE，CARLSARKISSIAN，ANDMANOJMONGA目的目的比較10種市售親水導(dǎo)絲的物理和機(jī)械性能方法方法進(jìn)行體外測(cè)試評(píng)估10種不同的直型親水導(dǎo)絲（5種普通導(dǎo)絲和5種硬導(dǎo)絲）GLIDEWIRE，NICORE，EZGLIDER，HIWIRE與ZIPWIRE。測(cè)量所有這10種導(dǎo)絲的頭端穿刺力，頭端彎曲力，桿彎曲力以及在運(yùn)動(dòng)中的摩擦力。采用高倍光學(xué)顯微鏡測(cè)量頭端輪廓。結(jié)果結(jié)果GLIDEWIRE穿刺我們的模型所需的力最大（P01）。EZGLIDER，ZIPWIRE和GLIDEWIRE頭端彎曲力最小（P＜001）。GLIDEWIRE桿最硬（P＜001）。EZGLIDER和GLIDEWIRE在摩擦力測(cè)試中力最大。就硬導(dǎo)絲而言，GLIDEWIRES在穿刺測(cè)試中力最大（P≤05）。GLIDEWIRES和EZGLIDERS頭端彎曲力最小。ZIPWIRES和NICORES桿最硬（P≤01）GLIDEWIRES在摩擦測(cè)試中力最大（P≤001）。頭端輪廓測(cè)試顯示ZIPWIRE，HIWIRES以及EZGLIDERS頭端最圓。結(jié)論結(jié)論每一種導(dǎo)線都有其獨(dú)特的優(yōu)點(diǎn)和缺點(diǎn)。雖然GLIDEWIRE（硬導(dǎo)絲和普通導(dǎo)絲兩種）潤(rùn)滑性較差，但是其刺穿的可能性最低。GLIDEWIRE和EZGLIDER頭端彎曲的力最小。在腔道泌尿外科手術(shù)過(guò)程中選擇正確的導(dǎo)絲可以幫助提高成功率，減少發(fā)病率。當(dāng)通過(guò)狹窄的輸尿管段或嵌頓結(jié)石時(shí)，可以使用親水性柔韌導(dǎo)絲繞過(guò)阻塞，不會(huì)發(fā)生穿孔或創(chuàng)傷。目前存在大量的市售導(dǎo)絲，每個(gè)都有其獨(dú)特的屬性，這些屬性可以影響它們的性能和潛在的發(fā)病率。導(dǎo)絲的功能是在輸尿管撕裂的情況下提供連續(xù)性和作為器械能夠通過(guò)的引導(dǎo)。由于術(shù)中對(duì)導(dǎo)絲的需求在不同情況下是不一樣的，可以使用各種不同的組成材料、形狀、桿剛性、潤(rùn)滑性，表面涂層、頭端設(shè)計(jì)和柔韌性的導(dǎo)絲?？紤]所有這些屬性是為臨床應(yīng)用選擇合適的導(dǎo)絲的關(guān)鍵。在遇到嚴(yán)重曲折、障礙物或嘗試用普通導(dǎo)絲失敗等復(fù)雜的情況下，親水導(dǎo)絲通常會(huì)被用來(lái)幫助疏通通道。這些導(dǎo)絲通常有一個(gè)堅(jiān)實(shí)的鎳鈦或金屬合金核心，以及持久的親水涂層，親水涂層顯著減少了其濕潤(rùn)時(shí)的摩擦系數(shù)。圖1A穿刺實(shí)驗(yàn)；B桿彎曲試驗(yàn)；C頭端彎曲試；D摩擦實(shí)驗(yàn)統(tǒng)計(jì)分析導(dǎo)絲被分為2組（普通VS硬），使用單向方差分析來(lái)確定各組中的各個(gè)測(cè)試的所有導(dǎo)絲之間的統(tǒng)計(jì)學(xué)差異。T檢驗(yàn)用于各試驗(yàn)中的導(dǎo)線之間的成對(duì)比較。使用MICROSOFTEXCEL分析工具庫(kù)（微軟，華盛頓州雷蒙德市）來(lái)分析所收集的數(shù)據(jù)。顯著性被定為P005。結(jié)果所有導(dǎo)絲的直徑為0889毫米，長(zhǎng)150厘米，帶3厘米軟頭。單因素方差分析結(jié)果顯示，在所有測(cè)試每個(gè)組內(nèi)導(dǎo)絲之間平均力測(cè)量有顯著的統(tǒng)計(jì)學(xué)差異（P0001表1）。普通硬導(dǎo)絲普通GLIDEWIRE刺穿我們的模型需要約的力量比其他導(dǎo)絲大約40（0363±0704N），其次是ZIPWIRE（0328±0085N，P340），EZGLIDER（0261±0071N，P06），HIWIRE（0259±0038N，P001），以及NICORE（0257±0048N，P01）。桿彎曲測(cè)試表明GLIDEWIRE最硬（0134±0005），明顯比其他導(dǎo)絲需要更大

簡(jiǎn)介：PROCNATLACADSCIUSAVOL95,PP8801–8805,JULY1998MEDICALSCIENCESMYOCYTEPROLIFERATIONINENDSTAGECARDIACFAILUREINHUMANSMITOTICINDEX?CYTOKINESISJANKAJSTURA?,ANNAROSALERI,NICOLETTAFINATO?,CARLADILORETO?,CARLOABELTRAMI?,ANDPIEROANVERSADEPARTMENTOFMEDICINE,NEWYORKMEDICALCOLLEGE,VALHALLA,NY10595AND?DEPARTMENTOFPATHOLOGY,UNIVERSITYOFUDINE33100,UDINE,ITALYCOMMUNICATEDBYEUGENEBRAUNWALD,PARTNERSHEALTHCARESYSTEM,INC,BOSTON,MA,MAY18,1998RECEIVEDFORREVIEWJANUARY14,1998ABSTRACTINTRODUCEDSEVERALDECADESAGO,THEDOGMAPERSISTSTHATCARDIACMYOCYTESARETERMINALLYDIFFERENTIATEDCELLSANDTHATDIVISIONOFMUSCLECELLSISIMPOSSIBLEINTHEADULTHEARTMORERECENTLY,NUCLEARMITOTICDIVISIONSINMYOCYTESOCCASIONALLYWERESEEN,BUTTHOSEOBSERVATIONSWERECHALLENGEDONTHEASSUMPTIONTHATTHERATEOFCELLPROLIFERATIONWASINCONSEQUENTIALFORACTUALTISSUEREGENERATIONMOREOVER,MITOSESWERENEVERDETECTEDINNORMALMYOCARDIUMHOWEVER,THEANALYSISOFROUTINEHISTOLOGICPREPARATIONSCONSTITUTEDTHEBASISFORTHEBELIEFTHATMYOCYTESWEREUNABLETOREENTERTHECELLCYCLEANDDIVIDE,IGNORINGTHELIMITATIONSOFTHESETECHNIQUESWEREPORTHEREBYCONFOCALMICROSCOPYTHAT14MYOCYTESPERMILLIONWEREINMITOSISINCONTROLHUMANHEARTSANEARLY10FOLDINCREASEINTHISPARAMETERWASMEASUREDINENDSTAGEISCHEMICHEARTDISEASE152MYOCYTESPERMILLIONANDINIDIOPATHICDILATEDCARDIOMYOPATHY131MYOCYTESPERMILLIONBECAUSETHELEFTVENTRICLECONTAINS58?109MYOCYTES,THESEMITOTICINDICESIMPLYTHAT812?103,882?103,AND760?103MYOCYTESWEREINMITOSISINTHEENTIREVENTRICULARMYOCARDIUMOFCONTROLHEARTSANDHEARTSAFFECTEDBYISCHEMICANDIDIOPATHICDILATEDCARDIOMYOPATHY,RESPECTIVELYADDITIONALLY,MITOSISLASTSLESSTHAN1HR,SUGGESTINGTHATLARGENUMBERSOFMYOCYTESCANBEFORMEDINTHENONPATHOLOGICANDPATHOLOGICHEARTWITHTIMEEVIDENCEOFCYTOKINESISINMYOCYTESWASOBTAINED,PROVIDINGUNEQUIVOCALPROOFOFMYOCYTEPROLIFERATIONITISAGENERALCONTENTIONTHATCARDIACMYOCYTESAREUNABLETODIVIDEINTHEADULTHEART1,2HOWEVER,QUANTITATIVERESULTSSUGGESTTHATANINCREASEINMYOCYTENUMBEROCCURSWITHSEVEREMYOCARDIALHYPERTROPHY3,4,BUTBECAUSEMITOSESINMYOCYTESWERENOTIDENTIFIED,THISDEFICIENCYLEDTODISBELIEFOFTHESEMORPHOMETRICRESULTSTHEOCCASIONALDETECTIONOFNUCLEARMITOTICDIVISIONSINTHEPATHOLOGICHEART5,6,WASCONSIDEREDOFNOVALUEINTERMSOFACTUALREGENERATIONOFMYOCARDIALMASSADDITIONALLY,MITOSESWERENEVEROBSERVEDINCONTROLMYOCARDIUMSIMILARLY,DOCUMENTATIONOFCYTOKINESISINMYOCYTESWASLACKINGISCHEMICANDIDIOPATHICDILATEDCARDIOMYOPATHIESINHUMANSARECHARACTERIZEDSTRUCTURALLYBYSEVEREMYOCARDIALSCARRINGCONSISTINGOFMULTIPLESITESOFREPLACEMENTFIBROSISANDDIFFUSEINTERSTITIALFIBROSIS7–10MOREOVER,AREASOFSEGMENTALFIBROSISAREPRESENTINALLCASESOFISCHEMICMYOPATHIES7,9SEGMENTAL,REPLACEMENT,ANDINTERSTITIALFIBROSISARETHECONSEQUENCEOFMYOCYTENECROSISHOWEVER,ADISCREPANCYEXISTSBETWEENTHEEXTENSIVECOLLAGENACCUMULATIONANDTHEMODESTREDUCTIONINTHENUMBEROFVENTRICULARMYOCYTESINTHEPOSTINFARCTEDHUMANHEART9THEDEPOSITIONOF1MM3OFCOLLAGENREFLECTSTHELOSSOF50?103MUSCLECELLS11,ANDTHEMAGNITUDEOFFIBROSISINENDSTAGEISCHEMICCARDIOMYOPATHYWOULDIMPLYANEARLY90DECREASEINTHETOTALNUMBEROFLEFTVENTRICULARMYOCYTES9CONVERSELY,DECREASESOFLESSTHAN30HAVEBEENREPORTED9THISDISCREPANCYISEVENMOREAPPARENTINIDIOPATHICDILATEDCARDIOMYOPATHYINWHICHMYOCARDIALFIBROSISISASSOCIATEDWITHPRESERVATIONOFTHENUMBEROFMYOCYTESINTHEVENTRICLES10UNDERSTANDINGOFTHECELLULARBASISOFWALLRESTRUCTURINGINTHEDISEASEDHEARTISCOMPLICATEDFURTHERBYTHEDOCUMENTATIONTHATPROGRAMMEDMYOCYTECELLDEATHOCCURSWITHVENTRICULARDECOMPENSATION12,13APOPTOSISDOESNOTRESULTINTISSUEFIBROSISDYINGMYOCYTESAREREMOVEDFROMNEIGHBORINGCELLSINTHEABSENCEOFANINFLAMMATORYREACTION14THESEPHENOMENA,INDICATINGSEVEREONGOINGNECROTICANDAPOPTOTICMYOCYTEDEATH,POINTTOTHEPOSSIBILITYTHATMYOCYTESARENOTTERMINALLYDIFFERENTIATEDANDCELLPROLIFERATIONMAYBESTIMULATEDINTHEPATHOLOGICHEARTIMMUNOCYTOCHEMISTRYANDCONFOCALMICROSCOPYWEREUSEDHERETOMEASUREAMITOTICINDEXINMYOCYTESOFHEARTSOBTAINEDFROMPATIENTSUNDERGOINGCARDIACTRANSPLANTATIONASARESULTOFCHRONICISCHEMICHEARTDISEASEANDDILATEDCARDIOMYOPATHYHEARTSCOLLECTEDATAUTOPSYWEREUSEDASCONTROLSMATERIALSANDMETHODSCARDIACCHARACTERISTICSTWENTYSEVENPATIENTSUNDERGOINGCARDIACTRANSPLANTATION,12FORISCHEMICAND15FORIDIOPATHICDILATEDCARDIOMYOPATHY,WERESTUDIEDTHEFIRSTGROUPINCLUDED11MALESANDONEFEMALE,WITHANAVERAGEAGEOF52?9YEARS,ANDTHESECOND11MALESANDFOURFEMALES,WITHANAVERAGEAGEOF55?11YEARSNINECONTROLHEARTS,SEVENMALESANDTWOFEMALES,WITHANAVERAGEAGEOF48?15YEARS,WERECOLLECTEDATAUTOPSYWITHIN15HRAFTERDEATHDEATHOCCURREDFROMCAUSESOTHERTHANCARDIOVASCULARDISEASEMITOTICINDEXINTHE27EXPLANTEDANDNINECONTROLHEARTS,SPECIMENSCOMPRISINGTHEENTIRETHICKNESSOFTHEANTERIORANDPOSTERIORASPECTSOFTHELEFTVENTRICULARWALLWEREOBTAINEDHALFWAYBETWEENTHEAPEXANDTHEBASEOFTHEHEARTSAMPLESWEREFIXEDINFORMALINANDEMBEDDEDINPARAFFINSECTIONSWERESTAINEDWITHPROPIDIUMIODIDE20?G?MLAND?SARCOMERICACTINANTIBODYCLONE5C5,SIGMATOVISUALIZEDNAANDMYOFIBRILLARSTRUCTURESTHESESECTIONSWEREEXAMINEDBYCONFOCALMICROSCOPYMRC1000,BIORADWITHANOPTICALSECTIONTHICKNESSOF057?MTHEPERCENTAGEOFMYOCYTENUCLEIUNDERGOINGMITOSISWASOBTAINEDBYSAMPLINGANUMBEROFMYOCYTENUCLEI,VARYINGFROM12,000TO67,000VALUESINCONTROLHEARTSWERE75,000AND230,000THEEVALUATIONOFAMITOTICINDEXININTERSTITIALCELLSINCLUDEDSEVENCASESWITHISCHEMICCARDIOMYOPATHY,FIVEWITHDILATEDCARDIOMYOPATHY,ANDFOURCONTROLHEARTSINEACHPATHOLOGICANDNORMALHEART30,000AND100,000NUCLEIWERESAMPLED,RESPECTIVELYDATACOLLECTIONANDANALYSISRESULTSAREPRESENTEDASMEAN?SDSIGNIFICANCEBETWEENTWOMEASUREMENTSWASDETERMINEDBYTHESTUDENT’STTEST,ANDINMULTIPLECOMPARISONSWASEVALUATEDBYTHEBONFERRONIMETHOD15P?005WASCONSIDEREDSIGNIFICANTTHEPUBLICATIONCOSTSOFTHISARTICLEWEREDEFRAYEDINPARTBYPAGECHARGEPAYMENTTHISARTICLEMUSTTHEREFOREBEHEREBYMARKED‘‘ADVERTISEMENT’’INACCORDANCEWITH18USC§1734SOLELYTOINDICATETHISFACT?1998BYTHENATIONALACADEMYOFSCIENCES00278424?98?9588015200?0PNASISAVAILABLEONLINEATHTTP??WWWPNASORG?TOWHOMREPRINTREQUESTSSHOULDBEADDRESSEDATDEPARTMENTOFMEDICINE,VOSBURGHPAVILION,ROOM302,NEWYORKMEDICALCOLLEGE,VALHALLA,NY105958801RESULTSPATIENTSALLPATIENTSHADNEWYORKHEARTASSOCIATIONFUNCTIONALCLASSIIIORIVLEFTANDRIGHTVENTRICULARWEIGHTSWERE189?26AND62?18G,RESPECTIVELY,INCONTROLS,281?51AND110?33G,RESPECTIVELY,INISCHEMICCARDIOMYOPATHY,AND362?129AND96?36G,RESPECTIVELY,INDILATEDCARDIOMYOPATHYTHE49P?005AND92P?0001INCREASEINLEFTVENTRICULARWEIGHT,AND77P?001AND55P?005INCREASEINRIGHTVENTRICULARWEIGHTWITHISCHEMICANDDILATEDCARDIOMYOPATHY,RESPECTIVELY,WERESIGNIFICANTTISSUESAMPLINGOFTHELEFTVENTRICLEWASRESTRICTEDTOREGIONSINWHICHAREASOFSCARRINGWERENOTMACROSCOPICALLYVISIBLEHOWEVER,SMALLFOCIOFREPLACEMENTFIBROSISANDDIFFUSEINTERSTITIALFIBROSISWEREPRESENTINTHETISSUESECTIONSFROMPATHOLOGICHEARTSAREASOFREPARATIVEANDINTERSTITIALFIBROSISOCCASIONALLYWERESEENINTHELEFTVENTRICLEOFCONTROLHEARTSCONFOCALMICROSCOPYSECTIONSOFMYOCARDIUMWERELABELEDWITHPROPIDIUMIODIDEAND?SARCOMERICACTINANTIBODYTHISANTIBODYISSPECIFICFORIBANDSOFCARDIACANDSKELETALMUSCLECELLSANDDOESNOTREACTWITHOTHERACTINISOFORMS16CONFOCALMICROSCOPYALLOWEDANACCURATEIDENTIFICATIONOFMITOSISINMYOCYTESCHROMOSOMESWEREDEPICTEDBYTHEGREENCOLORASSIGNEDTOPROPIDIUMIODIDEFLUORESCENCE,ANDMYOFIBRILLARSTRUCTURESWERERECOGNIZEDBYTHEREDCOLORASSIGNEDTOTHEFLUORESCENCEOF?SARCOMERICACTINANTIBODYLABELINGFIG1A–CILLUSTRATESANUCLEUSINMITOSISANDTWODAUGHTERCELLSATTHECOMPLETIONOFCYTOKINESISINAPATIENTAFFECTEDBYDILATEDCARDIOMYOPATHYINTHISLATTEREXAMPLE,THEAGGREGATESOFCHROMOSOMESMIRROREACHOTHERINTHETWONEWLYGENERATEDMYOCYTESFIG1ESHOWSALATEPROPHASETHATISCHARACTERIZEDBYTHEPRESERVATIONOFNUCLEARSHAPEINTHEABSENCEOFNUCLEARMEMBRANETWOMOREMYOCYTENUCLEIEXHIBITINGMETAPHASECHROMOSOMESAREDEPICTEDINFIG1DANDFTHEINITIALSEPARATIONOFCHROMOSOMESINFIG1DMAYCORRESPONDTOLATEMETAPHASEORONSETOFANAPHASETHESETHREEMITOTICFIGURESWEREFOUNDINACASEOFISCHEMICCARDIOMYOPATHY,DILATEDCARDIOMYOPATHY,ANDACONTROLHEART,RESPECTIVELYAMITOTICIMAGEINANINTERSTITIALCELLANDTHREEADDITIONALMITOSESINMYOCYTESAREDEPICTEDINFIG1G–LUNDIFFERENTIATEDCYTOPLASMSURROUNDINGTHENUCLEUSUNDERGOINGDIVISIONFIG1IWASOBSERVEDIN52OFTHECASES74OF142ORGANELLESBREAKUPINTOSMALLFRAGMENTSTOALLOWMOREUNIFORMDISTRIBUTIONOFTHESECOMPONENTSINTHETWODAUGHTERCELLSTHEDISTINCTIONBETWEENMYOCYTEANDNONMYOCYTENUCLEIWASEXTREMELYSIMPLE,BECAUSEINTERSTITIALCELLSWERENOTSTAINEDBY?SARCOMERICACTINANTIBODYANDONLYTHENUCLEUSCOULDBEIDENTIFIEDBYPROPIDIUMIODIDESTAININGFIG1G,H,ANDJ–LTHISWASAPPARENTINNONDIVIDINGANDDIVIDINGINTERSTITIALCELLSFIG1GTHEREWASNOAPPARENTDIFFERENCEINTHELOCALIZATIONOFMITOSESINTHEANTERIORANDPOSTERIORASPECTSOFTHELEFTVENTRICLEINCONTROLANDPATHOLOGICHEARTSTHEAVERAGEAREAOFMYOCARDIUMEXAMINEDBYCONFOCALMICROSCOPYINEACHPATIENTWAS609?240MM2INCONTROLS,327?193MM2INISCHEMICCARDIOMYOPATHY,AND341?194MM2INDILATEDCARDIOMYOPATHYCORRESPONDINGNUMBERSOFMYOCYTENUCLEICOUNTEDWERE141,136?56,699,38,854?16,766,AND36,013?17,134VALUESFORMYOCYTEMITOTICFIGURESWERE18?06,51?35,AND43?20,RESPECTIVELYTHESEDATAALLOWEDTHECOMPUTATIONOFAMYOCYTEMITOTICINDEXINEACHGROUPFIG2INNORMALLEFTVENTRICLES,ANAVERAGEOF14MYOCYTESPERMILLIONCELLSWEREUNDERGOINGMITOSIS,BUTAMUCHHIGHERMITOTICINDEXWASMEASUREDINPATHOLOGICHEARTSINISCHEMICCARDIOMYOPATHY,152MYOCYTESPERMILLIONWEREDIVIDING,ANDINDILATEDCARDIOMYOPATHY,131MYOCYTESPERMILLIONWEREINMITOSISTHESMALLDIFFERENCEBETWEENTHETWOGROUPSOFPATIENTSWITHCARDIACFAILUREWASNOTSIGNIFICANT,YIELDINGANAVERAGEVALUEOF140PROLIFERATINGMYOCYTESPERMILLIONCELLSINCOMPARISONWITHHEALTHYMYOCARDIUM,CARDIACFAILUREWASCHARACTERIZEDBYA10FOLDINCREASEINTHENUMBEROFDIVIDINGMYOCYTESP?00001NOGENDERDIFFERENCEINTHISPARAMETERCOULDBEDETECTEDTHEMITOTICINDEXININTERSTITIALCELLSWAS18?13PERMILLIONCELLSINCONTROLSN?4AND106?42PERMILLIONCELLSINFAILINGHEARTSN?12SEVENISCHEMICANDFIVEIDIOPATHICMYOPATHIESWITHRESPECTTOMYOCYTES140?50N?27,THE24LOWERVALUEININTERSTITIALCELLSWASNOTSIGNIFICANTDISCUSSIONCARDIACHYPERTROPHYINTHEEARLY1920S,ANATOMICALSTUDIESEMPHASIZEDTHEDIFFICULTIESOFDETECTINGMITOTICFIGURESINMYOCYTESAND,ONTHISBASIS,INTRODUCEDTHECONCEPTTHATMUSCLECELLPROLIFERATIONISABSENTINTHEADULT,FULLYDIFFERENTIATED,MAMMALIANMYOCARDIUM1MOREOVER,EXPERIMENTALRESULTSOFACUTECARDIACHYPERTROPHYINRODENTSDEMONSTRATEDTHEINABILITYOFMYOCYTESTOREENTERTHECELLCYCLE,SYNTHESIZEDNA,ANDUNDERGOMITOTICDIVISION17–19THESEOBSERVATIONSWERERESPONSIBLEFORTHECREATIONOFTHEDOGMATHAT,SHORTLYAFTERBIRTH,VENTRICULARMYOCYTESWITHDRAWPERMANENTLYFROMTHECELLCYCLEANDAREDESTINEDTODIEWITHOUT

簡(jiǎn)介：中文中文3500字出處出處CHOIWH,KWONSU,JWAYJ,ETALTHEPULMONARYEMBOLISMSEVERITYINDEXINPREDICTINGTHEPROGNOSISOFPATIENTSWITHPULMONARYEMBOLISMJKOREANJOURNALOFINTERNALMEDICINE,2009,242123127肺栓塞嚴(yán)重程度指數(shù)預(yù)測(cè)肺栓塞患者的預(yù)后分析肺栓塞嚴(yán)重程度指數(shù)預(yù)測(cè)肺栓塞患者的預(yù)后分析CHOIWH,KWONSU,JWAYJ,ETAL【摘要】背景/目的許多預(yù)后模型已經(jīng)被建立來(lái)幫助醫(yī)生做出醫(yī)療決定以更好的治療肺栓塞患者。在這些模型中，肺栓塞嚴(yán)重程度指數(shù)（PESI）已被證明是一個(gè)成功的急性肺栓塞患者危險(xiǎn)分層工具。然而，PESI，沒有被應(yīng)用在韓國(guó)的肺栓塞患者。方法在這項(xiàng)研究中的患者由仁濟(jì)大學(xué)一山白醫(yī)院進(jìn)行計(jì)算機(jī)斷層掃描，時(shí)間1999年12月至2007年3月。為病人進(jìn)行危險(xiǎn)分層使用的PESI。根據(jù)PESI計(jì)算死亡風(fēng)險(xiǎn)。結(jié)果在這項(xiàng)研究中，90例患者中，有10例為PESI，29例為PESIII類，22例Ⅲ類，8例IV級(jí)，10例V級(jí)。30天之后，在每個(gè)級(jí)別的死亡率分別為0，103，91，0和50％（P00016），而分別的醫(yī)院內(nèi)死亡率為48，138，136，125，和50％（P值00065）?？傮w死亡率為95，276，318，500和60％（P00019）。死亡率與PESI分級(jí)顯著相關(guān)。結(jié)論P(yáng)ESI分級(jí)被發(fā)現(xiàn)與30天死亡率，醫(yī)院內(nèi)死亡率和整體死亡率顯著相關(guān)。我們的數(shù)據(jù)表明的PESI可以被用來(lái)預(yù)測(cè)肺栓塞患者的預(yù)后和決定患者的治療。【關(guān)鍵詞】急性肺栓塞預(yù)后簡(jiǎn)介肺動(dòng)脈栓塞發(fā)生比較頻繁，在美國(guó)每年每10萬(wàn)人有23例1，但是，由于其臨床特點(diǎn)是非特異的，因此診斷肺栓塞不是容易的。進(jìn)而，如果沒有適當(dāng)?shù)闹委?，肺栓塞是致命的。因此，恰?dāng)?shù)膽岩珊瓦m當(dāng)?shù)脑u(píng)估對(duì)于預(yù)后是很重要的。一旦預(yù)后被預(yù)測(cè)，通過(guò)適當(dāng)?shù)闹委?，死亡率可以降低。雖然已經(jīng)取得了明確的肺栓塞的危險(xiǎn)因素分類及治療方法，預(yù)后指標(biāo)數(shù)據(jù)仍是相對(duì)少。然而，自2000年日內(nèi)瓦評(píng)分發(fā)現(xiàn)2和2005年肺栓塞嚴(yán)重性指數(shù)（PESI）3被提出，這兩種模型已被引入。PESI評(píng)分被證明具有更高的預(yù)測(cè)精度4。表面上，韓國(guó)人可能會(huì)有較少肺栓塞的危險(xiǎn)因素，如肥胖或深靜脈血栓形成，與西方人相比，并可能有較好的預(yù)后5,6。然而，在目前的較少有數(shù)據(jù)支持這一論斷。出于這個(gè)原因，我們分析了用的PESI3分析韓國(guó)肺栓塞患者的預(yù)后預(yù)測(cè)。方法病人選擇1999年12月至2007年3月，我們招收在仁濟(jì)大學(xué)的一山白醫(yī)院的195例確診為急性肺栓塞的住院病人或門診病人，根據(jù)韓國(guó)疾病指南（KCD）。在這些患者中，84診斷不充分（即沒有經(jīng)計(jì)算機(jī)斷層掃描（CT）證實(shí)肺栓塞），21人生存或死亡沒能由醫(yī)療記錄錄或電話或保存病歷中獲得，將他們排除在外。在這項(xiàng)研究中，共對(duì)90名患者進(jìn)行了評(píng)價(jià)。研究設(shè)計(jì)1999年12月，我們選擇經(jīng)胸部CT檢查證實(shí)肺栓塞的患者，對(duì)他們的醫(yī)療記錄進(jìn)行了分析。除了11項(xiàng)的被認(rèn)為包括在PESI指數(shù)中的項(xiàng)目外，還記錄了年齡，性別，既往病史，合并癥，臨床癥狀3。根據(jù)AUJESKY等人3提出的方法，分?jǐn)?shù)計(jì)算如下年齡每歲為1分，男性10分，心率110次/分鐘為20分，癌癥為30分，心臟衰竭10分，慢性肺疾病10分，收縮壓30次/分鐘為20分，體溫36℃為20分，精神狀態(tài)改變?yōu)?0討論肺栓塞患者的死亡率報(bào)告的各種各樣（從2％到95％）79。根據(jù)我們的數(shù)據(jù)，30天的死亡率為111％，而住院期間的死亡率為156％，總死亡率為300％。我們懷疑該報(bào)告的死亡率，因?yàn)槊總€(gè)病人有一些混雜因素，可能會(huì)影響他/她的預(yù)后，如不同的合并疾病和不同程度的肺栓塞。然而，很少有報(bào)告中均提到的因素，可以影響預(yù)后或肺栓塞的預(yù)測(cè)因素。要?jiǎng)?chuàng)建一個(gè)肺栓塞患者預(yù)后預(yù)測(cè)系統(tǒng)，日內(nèi)瓦評(píng)分22000年開發(fā)，PESI評(píng)分3在2005年首次提出。自那時(shí)以來(lái)，PESI評(píng)分已被證明是一個(gè)較好的預(yù)后模型4。AUJESKY等3報(bào)道，PESI評(píng)分IV級(jí)的患者30天的死亡率為08271％，意味著PESI評(píng)分越高的患者死亡率有增加的傾向。PESI被應(yīng)用于韓國(guó)，30天的死亡率，住院期間死亡率和總死亡率為060％。由于所有的結(jié)果都有顯著的意義，PESI預(yù)測(cè)韓國(guó)肺栓塞患者的預(yù)后是有意義的（30天死亡率P00016，住院死亡率P00065，整體死亡率P00019）。AUJESKY等人3斷言，PESI可以被用來(lái)確定低風(fēng)險(xiǎn)群體，并制定一個(gè)治療計(jì)劃。他們報(bào)告說(shuō)，PESI評(píng)分I和II的患者30天的死亡率為16％和35％以下。治療過(guò)程中出血的危險(xiǎn)肺動(dòng)脈栓塞復(fù)發(fā)的頻率要低一些。他們還聲稱，在I級(jí)和II級(jí)的患者，低分子量肝素可以安全地使用，即使在門診病人，這些患者實(shí)際上是一個(gè)低風(fēng)險(xiǎn)組10。然而，當(dāng)根據(jù)PESI計(jì)算韓國(guó)患者30天的死亡率，I級(jí)患者為0％，而II級(jí)患者為103％，組間有顯著差異。AUJESKY等報(bào)道3，PESI為II級(jí)的病人難以通過(guò)日間護(hù)理治療。住院期間死亡率（I級(jí)48％，Ⅱ級(jí)138％）（P0029）和總死亡率（I級(jí)95％，Ⅱ級(jí)276％）（P0115），但兩組之間的差異無(wú)統(tǒng)計(jì)學(xué)意義。這可能因?yàn)镻ESI評(píng)分I級(jí)患者21個(gè)，II級(jí)患者的數(shù)量為29人。因此，對(duì)于兩個(gè)PESIⅠ和Ⅱ級(jí)為低風(fēng)險(xiǎn)群體門診治療可能是危險(xiǎn)的。IIIV級(jí)的患者表現(xiàn)出了類似的30天死亡率，住院期間的死亡率和總死亡率。等級(jí)越高沒有死亡率增加的傾向（P0424，0995和0281），當(dāng)PESI評(píng)分IIIV被重新分組為中等風(fēng)險(xiǎn)組，分級(jí)越高，死亡率明顯增加（30天死亡率P00016→00003，住院死亡率P00065→00038，整體死亡率P00019→00034）。因此，如果的PESI分級(jí)被重新分為低危（I級(jí)），中危（IIIV級(jí)），高危（V級(jí)），可改善后預(yù)測(cè)指標(biāo)的便利性，可行性和準(zhǔn)確性。比較各組死亡率，在低，中，高危人群分別為0，82％和50％，而30天死亡率住院期間死亡率分別為48，131和50％。相比較而言，總死亡率為95，311，和60％（表2）。肺栓塞要確定合適的治療方案，最重要的考慮病人的血流動(dòng)力學(xué)穩(wěn)定和超聲心動(dòng)圖結(jié)果。在這項(xiàng)研究中，觀察右心室運(yùn)動(dòng)障礙三個(gè)75例患者采取了心電圖，值得注意的是，這些患者中1人是在PESIⅢ級(jí)和其他兩個(gè)人在IV級(jí)，表明所有實(shí)例發(fā)生在相對(duì)較高的PESI類。這表明，可以用來(lái)確定高危人群以及低風(fēng)險(xiǎn)人群治療方案。這項(xiàng)研究有任何追溯性研究，包括在病人的選擇和治療計(jì)劃不一致的內(nèi)在限制。根據(jù)患者組（N90），對(duì)他們來(lái)說(shuō)，死亡原因未分類的數(shù)量相對(duì)較少。然而，我們的研究結(jié)果的精度提高，只有那些情況下，肺栓塞，通過(guò)胸部CT確認(rèn)都包括在內(nèi)。此外，使用的電話使我們能夠進(jìn)行相對(duì)長(zhǎng)期隨訪，以確認(rèn)在30天的死亡率，以及死亡率住院期間總死亡率。這項(xiàng)研究表明，PESI是一個(gè)有用的預(yù)測(cè)，不只是30天的死亡率，也包括住院期間死亡率及總死亡率。風(fēng)險(xiǎn)組分類使用PESI可以預(yù)測(cè)不僅是30天的死亡率，也包括住院期間死亡率及總死亡率，這表明它是一個(gè)相對(duì)準(zhǔn)確的預(yù)后預(yù)測(cè)的指標(biāo)。

簡(jiǎn)介：中文中文3400字出處出處KILICKESMEZO,BAYRAMOGLUS,INCIE,ETALVALUEOFAPPARENTDIFFUSIONCOEFFICIENTMEASUREMENTFORDISCRIMINATIONOFFOCALBENIGNANDMALIGNANTHEPATICMASSESJJOURNALOFMEDICALIMAGINGRADIATIONONCOLOGY,2009,5315055表觀擴(kuò)散系數(shù)對(duì)肝臟良惡性腫塊的鑒別表觀擴(kuò)散系數(shù)對(duì)肝臟良惡性腫塊的鑒別KILICKESMEZO,BAYRAMOGLUS,INCIE,ETAL摘要我們研究的目的是探討使用并行成像技術(shù)的磁共振彌散加權(quán)成像（DWI）區(qū)分肝臟良性和惡性局灶性病變的價(jià)值。77例患者和65例健康對(duì)照者被納入研究中。DWI選取B值0，500和1000S/毫米2，計(jì)算出病灶及正常肝臟表觀擴(kuò)散系數(shù)（ADC）值。肝局灶性病變的ADC值如下單純性囊腫（316±01810?3毫米2／S），包蟲囊腫（258±05310?3毫米2／S），血管瘤（197±04910?3毫米2／S），轉(zhuǎn)移（114±04110?3毫米2／S）和肝細(xì)胞癌（HCC）（115±03610?3毫米2／S）。與正常肝平均ADC值（156±01410?3毫米2／S）相比，所有疾病組的ADC值差異均有統(tǒng)計(jì)學(xué)意義（P＜001）。血管瘤和肝癌轉(zhuǎn)移瘤間的ADC值也有統(tǒng)計(jì)上的顯著差異（P001），兩者與單純的包蟲囊腫間也有統(tǒng)計(jì)學(xué)差異（P＜0008。然而，HCC和轉(zhuǎn)移瘤之間有無(wú)統(tǒng)計(jì)學(xué)差異。目前的研究表明，ADC的測(cè)量對(duì)鑒別肝臟局灶性良、惡性病變有很大潛力。我們建議添加DWI序列在MR掃描中和肝臟病理定量鑒別檢測(cè)。前言磁共振成像是檢測(cè)肝臟彌漫性和局灶性病變及區(qū)分良惡性腫瘤的特性最準(zhǔn)確的方法，其反映了其對(duì)各種數(shù)據(jù)采集的基礎(chǔ)能力，如T1，T2和注射造影劑釓后的早期和晚期增強(qiáng)圖像。肝臟局灶性病變的表征是非常重要的，患者知道原發(fā)惡性腫瘤長(zhǎng)需與已知的常見良性肝臟局灶性病變及轉(zhuǎn)移灶相鑒別。在肝臟疾病的調(diào)查中，也由于磁共振成像缺少電離輻射，且釓螯合物與碘造影劑相比相對(duì)安全等以上兩個(gè)重要因素使MR成像優(yōu)先使用CT掃描。此外，DWI已經(jīng)成為一個(gè)新的無(wú)對(duì)比材料的診斷工具來(lái)檢測(cè)和區(qū)分惡性局灶性病變。4我們的目的是研究DWI是否有檢測(cè)和區(qū)分惡性腫瘤的轉(zhuǎn)移和原發(fā)性肝細(xì)胞癌的能力。這是我們的機(jī)構(gòu)2006年1月至2007年3月進(jìn)行了一項(xiàng)回顧性研究。77例患者（42名女性，35名男性；平均年齡，59歲）和65名健康對(duì)照者（35名女性，30名男性；平均年齡，35歲）與完全正常的肝臟MRI及實(shí)驗(yàn)室檢查患者的研究。研究方案是經(jīng)我們機(jī)構(gòu)的道德委員會(huì)批準(zhǔn)。所有患者的書面同意書已在研究開始之前獲得。統(tǒng)計(jì)分析統(tǒng)計(jì)分析所有的統(tǒng)計(jì)分析采用SPSSWINDOWS100分析。病例的ADC值表示為平均值±標(biāo)準(zhǔn)偏差。方差分析和配對(duì)樣本的測(cè)試也被用于腹部器官段進(jìn)行比較。一個(gè)P值小于005被認(rèn)為是表示統(tǒng)計(jì)上有顯著差異。結(jié)果結(jié)果所有患者行常規(guī)及彌散加權(quán)MR檢查表觀擴(kuò)散系數(shù)的值列為箱形圖。肝臟病變的平均ADC值為（表1）單純性囊腫，20例（316±01810?3毫米2／S）；包蟲囊腫，13例（258±05310?3毫米2／S）；血管瘤，15例（197±04910?3毫米2／S）；轉(zhuǎn)移，13例（114±04110?3毫米2／S）；與肝細(xì)胞癌（HCC）13例（115±03610?3毫米2／S）。與正常肝組平均ADC值相比，所有的疾病組的平均ADC值差異有統(tǒng)計(jì)學(xué)意義（156±01410?3毫米2／S），（P＜001）。肝臟血管瘤和肝癌轉(zhuǎn)移瘤的ADC值也有統(tǒng)計(jì)上的顯著差異，（P001），它們與單純的包蟲囊腫間也有統(tǒng)計(jì)學(xué)意義（P＜0008）。然而，HCC和轉(zhuǎn)移瘤之間差異無(wú)統(tǒng)計(jì)學(xué)意義。討論討論擴(kuò)散加權(quán)成像是用來(lái)描述水分子的隨機(jī)（布朗）運(yùn)動(dòng)。插入一個(gè)自旋回波脈沖序列的一個(gè)非常強(qiáng)大的雙極性梯度脈沖或梯度回波脈沖序列，MRI可以對(duì)在組織中的水分子的擴(kuò)散更敏感。在多細(xì)胞組織擴(kuò)散限制增加；相反，它減少了在大細(xì)胞外空間或破壞細(xì)胞膜的低細(xì)胞組織。7很多關(guān)于肝臟局灶性病變的擴(kuò)散特性的文章已經(jīng)被發(fā)表。大多數(shù)研究表明，良性病變的ADC值（囊腫、血管瘤）明顯高于惡性病變高細(xì)胞的惡性腫塊。與先前的研究中，我們發(fā)現(xiàn)肝囊腫有最高的ADC值，無(wú)限制運(yùn)動(dòng)的水分子。有人發(fā)現(xiàn)基于擴(kuò)散信號(hào)的不同，單純肝囊腫與其他病變有顯著的統(tǒng)計(jì)學(xué)差異。作者認(rèn)為這種差異是由于粘性包蟲囊腫由頭節(jié)，小鉤，氯化鈉，葡萄糖，蛋白質(zhì)，脂類和多糖的離子。同樣，我們也發(fā)現(xiàn)了單純肝囊腫與其他病變有顯著間有統(tǒng)計(jì)學(xué)差異。與以往的研究中相比，我們的研究表明，定性和定量指標(biāo)容易區(qū)分血管瘤、囊腫及惡性腫塊。血管瘤相比囊腫有較低的ADC值，這可能與血管瘤成分是相關(guān)的。陳等人的報(bào)道稱，DWI可以鑒別膿腫與囊性腫瘤。在這項(xiàng)研究中所有膿腫腔顯示有較低的ADC值與腫瘤壞死部分不重疊。

簡(jiǎn)介：中文中文4125字出處出處OKOCHIM,OHTAH,TANAKAT,ETALELECTROCHEMICALPROBEFORONCHIPTYPEFLOWIMMUNOASSAYIMMUNOGLOBULINGLABELEDWITHFERROCENECARBOALDEHYDEJBIOTECHNOLOGYKOJIMAETAL,2003LIMETAL,2002,2003SALEH和SOHN,2003SATOETAL,2002WANGETAL,1998,2002WANG和JIN,2003二茂鐵衍生物常被用來(lái)做免疫分析LIMETAL,2002,2003PADESTEETAL,2000WANGETAL,2002以及DNA雜化測(cè)定的（FIG1B）。在兩種方法中，未標(biāo)記的二茂鐵是通過(guò)YM30超濾而除去的。超濾常進(jìn)行1215次，直至二茂鐵的響應(yīng)峰消失。與IGG結(jié)合的二茂鐵數(shù)目的確定結(jié)合的二茂鐵數(shù)目的確定羊抗人IGEIGG結(jié)合的二茂鐵平均數(shù)目通過(guò)原子吸收光譜儀（AA6600G型號(hào)，SHIMAZU,KYOTO,JAPAN）檢測(cè)鐵離子濃度而測(cè)定。FCCOOH的水溶液作為鐵離子的標(biāo)準(zhǔn)溶液。IGG的濃度可以通過(guò)BCA蛋白質(zhì)分析方法檢測(cè)（SMITHETAL,1985）。蛋白質(zhì)的濃度是通過(guò)三次測(cè)定而最終確定。FCCHO標(biāo)記標(biāo)記IGG的ELISA分析分析將抗原溶液（10MM人抗原IGE，100ΜL/WELL）置于96孔的聚苯乙烯高密度檢測(cè)板（CORNINGGLASS,CORNING,NY）中，室溫下培育1小時(shí)。此板用含005％TWEEN20的PBS溶液沖洗三次，然后將200ΜL含有01％BSA（W/V）的PBS溶液加入每個(gè)孔中，室溫下培育1小時(shí)以抑制活性位點(diǎn)的非特異性吸收。經(jīng)過(guò)清洗步驟之后，加入10MM標(biāo)記FCCHO的羊抗人IGEIGG100ΜL，反應(yīng)1小時(shí)。然后再次清洗實(shí)驗(yàn)板，加入100ΜL的ALP兔抗羊IGG在PBS中稀釋100倍二次抗體，反應(yīng)1小時(shí)；每次親合反應(yīng)后，實(shí)驗(yàn)板用PBST洗三次。將ALP的底物魯米諾530，滴入每個(gè)孔中，然后用LUCY2ANTHOSLABTECINSTRUMENTS,SALZBURG,AUSTRIA檢測(cè)光的強(qiáng)度。

簡(jiǎn)介：THEPULMONARYEMBOLISMSEVERITYINDEXINPREDICTINGTHEPROGNOSISOFPATIENTSWITHPULMONARYEMBOLISMWONHOCHOI1,SUNGUKKWON1,2,YOONJUNGJWA1,JUNGAKIM1,YUNHOCHOI1,JEHOCHANG1,HOONJUNG1,JOONHYUNGDOH1,2,JUNENAMGUNG1,2,SUNGYUNLEE1,2ANDWONROLEE1,2DEPARTMENTSOF1INTERNALMEDICINEAND2VISION21CARDIAC24123127KEYWORDSPULMONARYEMBOLISMPROGNOSISRECEIVEDAPRIL13,2008ACCEPTEDJULY28,2008CORRESPONDENCETOSUNGUKKWON,MDDEPARTMENTOFINTERNALMEDICINE,INJEUNIVERSITYILSANPAIKHOSPITAL,2240DAEHWADONG,ILSANGU,GOYANG411706,KOREATEL82319107830,FAX82319107219,EMAILMDKSUILSANPAIKACKRINTRODUCTIONPULMONARYEMBOLISMSOCCURRELATIVELYFREQUENTLY,WITH23CASESPER100,000ANNUALLYINTHEUNITEDSTATES1HOWEVER,SINCEITSCLINICALFEATURESARENONSPECIFIC,ADIAGNOSISOFPULMONARYEMBOLISMISNOTEASYTOMAKEFURTHERMORE,WITHOUTAPPROPRIATETREATMENT,APULMONARYEMBOLISMCANBEFATALTHEREFORE,SUSPECTINGSUCHACONDITIONANDEVALUATINGITAPPROPRIATELYISIMPORTANTINMAKINGAPROGNOSISONCEAPROGNOSISHASBEENMADE,THEMORTALITYRATECANBELOWEREDTHROUGHPROPERTREATMENTHOWEVER,WHILESIGNIFICANTEFFORTHASBEENMADETOCLARIFYTHERISKFACTORSANDTREATMENTOFPULMONARYEMBOLISM,RELATIVELYLITTLEDATAAREAVAILABLEREGARDINGAPROGNOSTICINDEXNEVERTHELESS,SINCETHEDEVELOPMENTOFTHEGENEVASCORE2IN2000ANDTHEPULMONARYEMBOLISMSEVERITYINDEXPESI3IN2005,TWOMODELSHAVEBEENINTRODUCEDASPROGNOSTICPREDICTIVEINDEXESOFTHESE,THEPESIHASBEENSHOWNTOHAVEHIGHERPREDICTIVEACCURACY4OSTENSIBLY,KOREANSMAYAPPEARTOHAVEFEWERRISKFACTORSFORPULMONARYEMBOLISM,SUCHASOBESITYORDEEPVEINTHROMBOSIS,COMPAREDTOPEOPLEINTHEWEST,ANDMAYTHUSBEEXPECTEDTOSUFFERFROMPULMONARYEMBOLISMS133HADDIABETES,AND16178HADEITHERBEENDIAGNOSEDWITHCANCERORWEREBEINGTREATEDFORCANCERNINEPATIENTS10WERECONFIRMEDASHAVINGEMPHYSEMATHROUGHCHESTCT,WHILETENPATIENTS111HADACEREBRALHEMORRHAGEANDCEREBRALINFARCTION,AND26289HADASURGICALHISTORYTABLE1PESICLASSIFICATICHWITHREGARDTOTHEDISTRIBUTIONOFTHEPATIENTSACCORDINGTOTHEIRPESIRISKCLASS,2123,3465POINTS,AVERAGE499POINTSPATIENTSWEREINCLASSI126PESIPOINTSTHUS,MOSTOFTHEPATIENTSWEREINCLASSIIWHILETHESMALLESTNUMBERWEREINCLASSIVFIG1MORTALITYRATEBASEONTHEPESITHEMORTALITYRATEAFTER30DAYS,MORTALITYRATEDURINGHOSPITALIZATION,ANDTOTALMORTALITYRATEWERECOMPAREDACCORDINGTOTHEPESIRISKCLASSESOFTHEPATIENTSAT30DAYS,THEMORTALITYRATEWAS111WHENTHISRESULTWASANALYZEDACCORDINGTOPESICLASS,ASIGNIFICANTTRENDTOWARDINCREASEDMORTALITYWITHAHIGHERCLASSWASDETECTEDP00016,WITH0INCLASSI,103INCLASSII,91INCLASSIII,0INCLASSIV,AND50INCLASSVINCONSIDERINGTHE0MORTALITYRATEDETECTEDFORCLASSIV,NOTETHATTHEAVERAGEHOSPITALSTAYFORTHISGROUPWAS10DAYSSHORTERTHANTHATFORTHEOTHERGROUPSTHUS,THEPOSSIBILITYOFUNDERESTIMATIONEXISTSINCOMPARISON,THEHOSPITALMORTALITYRATEWAS156WHENITWASANALYZEDACCORDINGTOPESICLASS,ASIGNIFICANTTRENDP00065WASOBSERVED,WITH48INCLASSI,138INCLASSII,136INCLASSIII,125INCLASSIV,AND50INCLASSVFIG2THETOTALMORTALITYRATEWAS30WHENITWASANALYZEDACCORDINGTOPESICLASS,ANINCREASINGTENDENCYTOWARDTHEHIGHERCLASSWASOBSERVED,WITH95INCLASSI,276INCLASSII,318INCLASSIII,50INCLASSIV,AND60INCLASSVP00019FIG3MORTALITYRATEOFTHEREDISTRIBUTEDPESIGROUPINGOFTHEPESICLASSESINTOLOWCLASSI,INTERMEDIATECLASSESIIIV,ANDHIGHRISKCLASSVGROUPSPRODUCEDA30DAYMORTALITYRATEOF0,82,AND50,RESPECTIVELYCOMPAREDTOTHERESULTSBEFORETHEREDISTRIBUTION,THETENDENCYWASQUITECLEARP00016→00003THEMORTALITYRATEDURINGHOSPITALIZATIONWAS48,131,AND50FORTHELOW,INTERMEDIATE,ANDHIGHRISKGROUPS,RESPECTIVELY,ANDTHETENDENCYWASMUCHCLEARERP00065→00038,ASWASTHE30DAYMORTALITYRATETHETOTALMORTALITYRATEWAS95,311,AND60FORTHELOW,INTERMEDIATE,ANDHIGHRISKGROUPS,RESPECTIVELY,CHOIWH,ETALUSEOFPESITOPREDICTPROGNOSISOFPULMONARYEMBOLISM125FIGURE1PATIENTSDISTRIBUTIONACCORDINGTOPESIRISKCLASS23N2132N2925N229N811N10CLASSICLASSIICLASSIIICLASSIVCLASSVFIGURE2HOSPITALMORTALITYACCORDINGTOPESIRISKCLASSIFICATIONPESI,PULMONARYEMBOLISMSEVERITYINDEXNS,NOTSIGNIFICANT5000000000000000CLASSICLASSIICLASSIIICLASSIVCLASSVHOSPITALMORTALITYP0026PNS4808013601250PFIGURE3OVERALLMORTALITYACCORDINGTOPESIRISKCLASSIFICATIONPESI,PULMONARYEMBOLISMSEVERITYINDEXNS,NOTSIGNIFICANT6000P00000000000000CLASSICLASSIICLASSIIICLASSIVCLASSVOVERALLMORTALITYP0038PNS950603180P00

簡(jiǎn)介：SAGEHINDAWIACCESSTORESEARCHMOLECULARBIOLOGYINTERNATIONALVOLUME2011,ARTICLEID437301,7PAGESDOI104061/2011/437301REVIEWARTICLEMIR146AINIMMUNITYANDDISEASENICOLERUSCAANDSILVIAMONTICELLIINSTITUTEFORRESEARCHINBIOMEDICINE,VIAVINCENZOVELA6,6500BELLINZONA,SWITZERLANDCORRESPONDENCESHOULDBEADDRESSEDTOSILVIAMONTICELLI,SILVIAMONTICELLIIRBUNISICHRECEIVED17DECEMBER2010ACCEPTED17FEBRUARY2011ACADEMICEDITORALESSANDRODESIDERICOPYRIGHT?2011NRUSCAANDSMONTICELLITHISISANOPENACCESSARTICLEDISTRIBUTEDUNDERTHECREATIVECOMMONSATTRIBUTIONLICENSE,WHICHPERMITSUNRESTRICTEDUSE,DISTRIBUTION,ANDREPRODUCTIONINANYMEDIUM,PROVIDEDTHEORIGINALWORKISPROPERLYCITEDMICRORNASMIRNASAREREGULATORYMOLECULESABLETOINFLUENCEALLASPECTSOFTHEBIOLOGYOFACELLTHEYHAVEBEENASSOCIATEDWITHDISEASESSUCHASCANCER,VIRALINFECTIONS,ANDAUTOIMMUNEDISEASES,ANDINRECENTYEARS,THEYALSOEMERGEDASIMPORTANTREGULATORSOFIMMUNERESPONSESMIR146AINPARTICULARISRAPIDLYGAININGIMPORTANCEASAMODULATOROFDIFFERENTIATIONANDFUNCTIONOFCELLSOFTHEINNATEASWELLASADAPTIVEIMMUNITYGIVENITSIMPORTANCEINREGULATINGKEYCELLULARFUNCTIONS,ITISNOTSURPRISINGTHATMIR146AEXPRESSIONWASALSOFOUNDDYSREGULATEDINDIFFERENTTYPESOFTUMORSINTHISPAPER,WESUMMARIZERECENTPROGRESSINUNDERSTANDINGTHEROLEOFMIR146AININNATEANDADAPTIVEIMMUNERESPONSES,ASWELLASINDISEASE1INTRODUCTIONMICRORNASMIRNASREPRESENTAPERVASIVEFEATUREOFALLCELLS,ASTHEYREGULATELARGEFRACTIONSOFTHECELL’STRANSCRIPTOMESOFAR,672MOUSEMIRNASAND1048HUMANMIRNASHAVEBEENDESCRIBEDINTHEMIRBASEDATABASEHTTP//WWWMIRBASEORG/,RELEASESEPT2010WITHEACHMIRNAPOTENTIALLYREGULATINGTHEEXPRESSIONOFHUNDREDSOFTARGETGENES,HIGHLIGHTINGTHEEXTENTOFTHISFORMOFREGULATION1WHEREASSOMEMIRNASAREWIDELYEXPRESSED,OTHERSEXHIBITONLYLIMITEDDEVELOPMENTALSTAGE,TISSUE,ORCELLTYPESPECIFICPATTERNS2SIMILARTOANYOTHERMAMMALIANCELLTYPE,CELLSOFTHEIMMUNESYSTEMRELYONMIRNASTOREGULATELINEAGECOMMITMENT,PROLIFERATION,MIGRATION,ANDDIFFERENTIATIONINMOSTCASES,THESEACTIVITIESAREORCHESTRATEDBYBOTHUBIQUITOUSLYEXPRESSEDANDCELLTYPESPECIFICMIRNASPECIES3–7THEIMPORTANCEOFMIRNASINREGULATINGDIFFERENTIATIONANDFUNCTIONOFIMMUNECELLSISUNDERLINEDBYTHEPHENOTYPICALPERTURBATIONSTHATOCCURWHENMIRNAEXPRESSIONISALTEREDGIVENTHEEMERGINGROLESOFMIRNASINMODULATINGIMMUNERESPONSES,ITISLIKELYTHATANYDYSREGULATIONOFMIRNAEXPRESSIONMAYCONTRIBUTETOTHEPATHOGENESISOFAUTOIMMUNEDISEASES,CHRONICINFLAMMATION,ANDMALIGNANCIESINDEED,SEVERALHUMANDISEASESHAVENOWBEENASSOCIATEDWITHDYSREGULATEDMIRNAEXPRESSION,ANDMIRNASHAVEBEENSHOWNTOFUNCTIONBOTHASONCOGENESANDTUMORSUPPRESSORGENES8,9MIR146AHASBEENRECENTLYSHOWNTOBEANIMPORTANTMODULATOROFDIFFERENTIATIONANDFUNCTIONOFCELLSOFINNATEASWELLASADAPTIVEIMMUNITYHERE,WESUMMARIZERECENTPROGRESSINUNDERSTANDINGTHEROLEOFMIR146AINIMMUNERESPONSESANDINDISEASESEEALSOTABLE12WHATAREMICRORNASMIRNASARESMALL20–25NUCLEOTIDES,NONCODINGRNAMOLECULESINVOLVEDINPOSTTRANSCRIPTIONALGENEREGULATIONTHEYDERIVEFROMPRIMARYTRANSCRIPTSPRIMIRNATHATAREPROCESSEDINTOHAIRPINPRECURSORSPREMIRNASWITHINTHENUCLEUSOFTHECELLBYTHEMICROPROCESSORCOMPLEX,WHICHINCLUDESTHERNASEIIIENZYMEDROSHAPREMIRNASARETRANSLOCATEDINTOTHECYTOPLASMANDPROCESSEDBYDICERINTOTHEIRMATUREFORMFORARECENTREVIEWSEE25ANEXCEPTIONTOTHISRULEISREPRESENTEDBYTHELESSABUNDANT“MIRTRONS”,THATBYPASSDROSHAANDAREPROCESSEDONLYBYDICER26MATUREMIRNASLOADEDONTOTHERNAINDUCEDSILENCINGCOMPLEXRISCRECOGNIZESITESLOCATEDMOSTLYINTHE3?UNTRANSLATEDREGION3?UTROFTARGETMRNASTHROUGHCANONICALBASEPAIRINGBETWEENTHESEEDSEQUENCEOFTHEMIRNANUCLEOTIDES2–8ATITS5?ENDANDITSCOMPLEMENTARYSEQUENCEINTHETARGETMRNATHISLEADSTOABLOCKINTRANSLATIONWITHORWITHOUTDESTABILIZATIONANDDEGRADATIONOFTHETARGETEDMRNAMIRNASMODULATEAMOLECULARBIOLOGYINTERNATIONAL3TCELLSUBSETSINDEED,TCELLSLACKINGDICERSHOWEDINCREASEDDIFFERENTIATIONTOTHETH1SUBSETWITHACORRESPONDINGLYREDUCEDPOLARIZATIONTOTH229ADDINGTOTHECOMPLEXITYOFGENEREGULATORYNETWORKS,PROLIFERATINGTCELLSEXPRESSGENESWITHSHORTER3?UTRSTHANTHOSEEXPRESSEDINRESTINGTCELLS,MAKINGTHESEMRNASLESSSUSCEPTIBLETOREGULATIONBYMIRNASDUETOTHELOSSOFMIRNABINDINGSITES41FINALLY,INDIVIDUALMIRNASWEREALSOSHOWNTOPLAYIMPORTANTROLESINTCELLDIFFERENTIATIONANDFUNCTIONFOREXAMPLE,MIR181A,WHICHISUPREGULATEDDURINGTCELLDEVELOPMENT,WASSHOWNTOENHANCETCELLRECEPTORTCRSIGNALLINGSTRENGTHBYDIRECTLYTARGETINGANUMBEROFPROTEINPHOSPHATASES32,WHILEMICELACKINGMIR155SHOWEDANALTEREDTH1/TH2POLARIZATIONWITHABIASTOWARDSTH2,INDICATINGTHATMIR155PROMOTESDIFFERENTIATIONTOWARDSTH1CELLS35ASFORTHEROLEOFMIR146AINTCELLS,BYANALYZINGTHEEXPRESSIONOFMIRNASINHIGHLYPURIFIEDSUBSETSOFCELLSOFTHEIMMUNESYSTEM,WESHOWEDTHATMIR146AISONEOFTHEVERYFEWMIRNASDIFFERENTIALLYEXPRESSEDBETWEENTH1ANDTH2CELLSINTHEMOUSE,SUGGESTINGTHATITMIGHTBEINVOLVEDINFATEDETERMINATIONOFTHESECELLS5RECENTWORKPERFORMEDINMIR146ADEFICIENTMICESHOWEDANINCREASEINTHEPERCENTAGEOFINFΓPRODUCINGTCELLSUBSETINTHEABSENCEOFMIR146A10INHUMANTCELLS,MIR146AISEXPRESSEDATLOWLEVELSINNA¨IVETLYMPHOCYTESWHILEITISABUNDANTLYEXPRESSEDINMEMORYTCELLSANDITISINDUCEDUPONTCRSTIMULATION,CONSISTENTWITHITSEXPRESSIONBEINGDEPENDENTONNFΚBINDUCTION12,13INDEED,NFΚBANDCETSBINDINGSITESWERESHOWNTOBEREQUIREDFORTHEINDUCTIONOFMIR146ATRANSCRIPTIONINHUMANTCELLS,ANDSUCHINDUCTIONPOTENTIALLYMODULATEDCELLDEATHINTHESECELLSBYTARGETINGFADDANDBYIMPAIRINGBOTHAP1ACTIVITYANDIL2PRODUCTION13TREGCELLSCONSTITUTEASPECIALIZEDTCELLSUBSETABLETOMAINTAINIMMUNEHOMEOSTASISBYLIMITINGTHEINFLAMMATORYRESPONSES,ANDTHEIRSUPPRESSIVEFUNCTIONISINDISPENSABLEFORIMMUNEHOMEOSTASISANDSURVIVALOFHIGHERORGANISMSRECENTLY,LUANDCOLLEAGUESREPORTEDTHATMIR146AISAMONGTHEMIRNASPREVALENTLYEXPRESSEDINTREGCELLSANDSHOWEDTHATITISCRITICALFORTREGFUNCTIONSINDEED,DEFICIENCYOFMIR146ARESULTEDININCREASEDNUMBERSBUTIMPAIREDFUNCTIONOFTREGCELLSANDASACONSEQUENCE,BREAKDOWNOFIMMUNOLOGICALTOLERANCEWITHMASSIVELYMPHOCYTEACTIVATION,ANDTISSUEINFILTRATIONINSEVERALORGANS10THEIMMUNEMEDIATEDLESIONSINDUCEDBYTHELACKOFMIR146AINTREGSWEREDEPENDENTONINFΓANDSTAT14MIR146ININNATEIMMUNITYANDNONIMMUNESYSTEMSCELLSOFTHEINNATEIMMUNESYSTEM,SUCHASGRANULOCYTES,NATURALKILLERNKCELLS,MONOCYTES,ANDMACROPHAGES,PROVIDEANIMPORTANTFIRSTLINEOFDEFENSEFORTHEORGANISMAGAINSTINVADINGPATHOGENSMIRNASHAVEBEENIMPLICATEDINBOTHTHEDEVELOPMENTANDFUNCTIONSOFINNATEIMMUNECELLSFOREXAMPLE,THEMACROPHAGEINFLAMMATORYRESPONSETOINFECTIONINVOLVESTHEUPREGULATIONOFSEVERALMIRNAS,SUCHTLR4ADAPTERMOLECULESIKKCOMPLEXPPIRAK1TRAF6CYTOPLASMNUCLEUSPRIMIR146AMIR146ARISCCOMPLEXIΚBΑNFΚBNFΚBFIGURE1MIR146ANEGATIVELYREGULATESSIGNALTRANSDUCTIONPATHWAYSLEADINGTONFΚBACTIVATIONUPONACTIVATIONOFACELLSURFACERECEPTORSUCHASTLR4,AMOLECULARCASCADEINCLUDINGTRAF6ANDIRAK1LEADSTOIΚBΑPHOSPHORYLATIONANDDEGRADATIONANDTONFΚBACTIVATIONANDNUCLEARTRANSLOCATION12,42NFΚBACTIVATIONINDUCESTRANSCRIPTIONOFMANYGENES,INCLUDINGPRIMIR146AONCETRANSLOCATEDTOTHECYTOPLASMANDLOADEDONTOTHERISCCOMPLEX,MATUREMIR146ACONTRIBUTESTOATTENUATERECEPTORSIGNALINGTHROUGHTHEDOWNMODULATIONOFIRAK1ANDTRAF6ASMIR155,MIR146,MIR147,MIR21,ANDMIR912,43–46SEVERALSTUDIESLINKEDMIR146AEXPRESSIONTONFΚBSIGNALINGWITHINTHEINNATEIMMUNESYSTEMFIGURE1ANDWEREINITIATEDBYASTUDYSHOWINGTHATMIR146AISQUICKLYINDUCEDUPONACTIVATIONOFHUMANMONOCYTES12INTHISSTUDY,MIR146AWASFOUNDTOBEINDUCIBLEUPONSTIMULATIONWITHLPSINANFΚBDEPENDENTMANNER,ANDTOTARGETTHETNFRECEPTORASSOCIATEDFACTOR6TRAF6ANDIL1RECEPTORASSOCIATEDKINASE1IRAK1GENESTHESEGENESENCODETWOKEYADAPTERMOLECULESDOWNSTREAMOFCYTOKINEANDTOLLLIKERECEPTORSTLR,POINTINGTOWARDSAROLEFORMIR146AINCONTROLLINGSIGNALINGFROMTHESERECEPTORSTHROUGHANEGATIVEFEEDBACKREGULATORYLOOPINVOLVINGDOWNREGULATIONOFTRAF6ANDIRAK112ITWASALSOSUGGESTEDTHATMIR146ACONTRIBUTESTOTHEESTABLISHMENTOFENDOTOXINTOLERANCEINMONOCYTESANDTOTHEREGULATIONOFTNFΑPRODUCTION14INTHISCONTEXT,MIR146AWOULDTHEREFOREACTASATUNINGMECHANISMTOPREVENTANOVERSTIMULATEDINFLAMMATORYSTATEINHUMANLANGERHANSCELLSLCS,MIR146AWASFOUNDTOBECONSTITUTIVELYEXPRESSEDATHIGHLEVELS,ASCOMPAREDTOINTERSTITIALDENDRITICCELLSINTDCS15INTHESECELLS,HIGHMIR146AEXPRESSIONWASINDUCEDBYTHETRANSCRIPTIONFACTORPU1INRESPONSETOTGFΒ1,AKEY

簡(jiǎn)介：中文中文5200字出處出處KAJSTURAJ,LERIA,FINATON,ETALMYOCYTEPROLIFERATIONINENDSTAGECARDIACFAILUREINHUMANSJPROCEEDINGSOFTHENATIONALACADEMYOFSCIENCES,1998,951588018805心臟衰竭末期的心肌細(xì)胞再生心臟衰竭末期的心肌細(xì)胞再生KAJSTURAJ,LERIA,FINATON,DILORETOC,BELTRAMICA,ANVERSAP前言前言在幾十年前，人們一直堅(jiān)信心肌細(xì)胞是一種終極分化細(xì)胞，在成人心臟中心肌細(xì)胞分裂是不可能的。然而最近，偶爾有在心肌細(xì)胞中發(fā)現(xiàn)細(xì)胞核有絲分裂的報(bào)道，但是這種發(fā)現(xiàn)被一種假設(shè)所質(zhì)疑如果心肌細(xì)胞存在有絲分裂，但現(xiàn)實(shí)中的卻沒有心肌組織再生。此外，心肌細(xì)胞有絲分裂的現(xiàn)象從來(lái)沒有在正常心肌細(xì)胞中被發(fā)現(xiàn)。然而，通過(guò)分析常規(guī)的組織組成的基礎(chǔ)需求，忽略設(shè)備的限制，確信心肌細(xì)胞沒有能力進(jìn)入細(xì)胞周期及細(xì)胞分裂。在這里我們的研究通過(guò)顯微鏡發(fā)現(xiàn)在每100萬(wàn)個(gè)心肌細(xì)胞中有14個(gè)在進(jìn)行有絲分裂。在在缺血性心臟疾病及先天性擴(kuò)張型心肌病中這個(gè)數(shù)字將是正常心臟的10倍（在缺血性心臟病中每100萬(wàn)個(gè)心肌細(xì)胞中有152個(gè)，在先天性擴(kuò)張性心肌病中每100萬(wàn)個(gè)心肌細(xì)胞中有131個(gè)）。由于左心室大約有58109個(gè)心肌細(xì)胞，這些有絲分裂指數(shù)暗示在正常心肌，缺血性心肌病及先天性心肌病的整個(gè)左心室中將分別有812103,882103,76103個(gè)心肌細(xì)胞在進(jìn)行有絲分裂。與此同時(shí)，有絲分裂時(shí)間通常少于一小時(shí)，提示在非病理及病理心臟中隨時(shí)間發(fā)展將有大量的心肌細(xì)胞生成。我們已經(jīng)發(fā)現(xiàn)了細(xì)胞質(zhì)分裂的證據(jù)，這清楚地證明了心肌細(xì)胞有絲分裂的存在。心肌細(xì)胞在成人心臟中是否能夠分裂一直是人們爭(zhēng)論的話題。然而大量證據(jù)提示在心肌嚴(yán)重肥厚時(shí)存在心肌細(xì)胞數(shù)目大量增長(zhǎng)，但是心肌細(xì)胞是否進(jìn)行有絲分裂卻沒有被證實(shí)，這個(gè)證據(jù)的缺乏質(zhì)疑了體視學(xué)結(jié)論的可信性。偶有發(fā)現(xiàn)在有病理性心臟疾病的心臟中存在細(xì)胞核的有絲分裂，但是這個(gè)發(fā)現(xiàn)對(duì)證實(shí)心肌細(xì)胞的大量再生沒有任何價(jià)值。另外，心肌細(xì)胞的有絲分裂從沒有在正常心臟的心肌細(xì)胞中發(fā)現(xiàn)。于此同時(shí)，心肌細(xì)胞細(xì)胞質(zhì)的有絲分裂證據(jù)也是不足的。人類缺血性心臟疾病及先天性擴(kuò)張性心臟疾病的結(jié)構(gòu)特征是由多處心肌纖維化及彌漫性的間質(zhì)纖維化構(gòu)成的心肌瘢痕。此外，在心肌缺血所有樣本中都有發(fā)現(xiàn)纖維片段。心肌細(xì)胞的壞死導(dǎo)致了纖維片段、纖維替代及間質(zhì)纖維化的現(xiàn)象。然而，大量膠原的積累與梗死后人左心室心肌細(xì)胞的大量減少出現(xiàn)明顯的差異。每減少1MM3的膠原反映了大約50103心肌細(xì)胞的丟失，在缺血性心肌病末期，大量纖維化暗示了大約有90的心肌細(xì)胞減少。相反的，曾經(jīng)報(bào)道實(shí)際心肌細(xì)胞的減少小于30。這種差異在先天性擴(kuò)張性心肌病中更加明顯。在有先天性擴(kuò)張性心肌病患者的心室肌中心肌纖維化，但是心肌細(xì)胞的數(shù)目卻沒有減少。在細(xì)胞基礎(chǔ)層面上研究疾病心臟的的心肌重塑機(jī)制是非常復(fù)雜的，遠(yuǎn)遠(yuǎn)超出心室的失代償導(dǎo)致的心肌細(xì)胞程序化死亡這樣的解釋。細(xì)胞凋亡不會(huì)導(dǎo)致組織纖維化；死亡的細(xì)胞被周圍細(xì)胞清除因此不會(huì)有炎癥反應(yīng)的發(fā)生。在嚴(yán)重的心肌細(xì)胞死亡及凋亡中，這些現(xiàn)象指出心肌細(xì)胞可能不是終極分化細(xì)胞，細(xì)胞的再生可能由病理性刺激誘導(dǎo)。我們用免疫細(xì)胞化學(xué)及共焦顯微鏡來(lái)計(jì)算由于慢性缺血性心臟病機(jī)擴(kuò)張性心肌病而需進(jìn)行心臟移植的患者的心臟心肌細(xì)胞的有絲分裂指數(shù)。用來(lái)做解剖的心臟都是受法律保護(hù)的。性心肌病組327±193MM2，在擴(kuò)張性心肌病組341±194MM2相應(yīng)的細(xì)胞核的數(shù)目分別為14136±56699,38854±16766，36013±17134細(xì)胞分裂指數(shù)分別為18±06,51±35,43±20用這些數(shù)據(jù)可以估算在各個(gè)組中心肌細(xì)胞的有絲分裂指數(shù)。在正常的左心室中平均每100萬(wàn)個(gè)心肌細(xì)胞有14個(gè)心肌細(xì)胞在進(jìn)行有絲分裂，但在病理心臟左心室中這個(gè)指數(shù)要高得多。在缺血性心肌病中平均每100萬(wàn)個(gè)心肌細(xì)胞中有152個(gè)在進(jìn)行有絲分裂，在擴(kuò)張性心肌病中每100萬(wàn)中有131個(gè)心肌細(xì)胞在進(jìn)行有絲分裂。在有心臟衰竭的這兩組患者中這種指數(shù)很小的差別沒有意義，平均一下每100萬(wàn)個(gè)心肌細(xì)胞中有140個(gè)心肌細(xì)胞在進(jìn)行著有絲分裂。與健康心肌相比，有絲分裂細(xì)胞數(shù)目在有心臟衰竭的患者總是正常健康人的10倍。實(shí)驗(yàn)中沒有性別差異。在正常組有絲分裂指數(shù)為18±13/100萬(wàn)細(xì)胞中，在衰竭的心臟中有106±42/100萬(wàn)心肌細(xì)胞中。（N127個(gè)缺血性心肌病，5個(gè)先天性心肌?。?。與心肌細(xì)胞相比，間質(zhì)細(xì)胞有絲分裂指數(shù)下降24是沒有意義的。討論討論心肌肥厚心肌肥厚在20世紀(jì)20年代初，在許多解剖研究中都強(qiáng)調(diào)，在心肌細(xì)胞中檢測(cè)核分裂有許多困難，并在此基礎(chǔ)上，介紹了細(xì)胞的增殖在成人、完全分化的生物及哺乳動(dòng)物的心肌中是不存在的的概念（1）。此外，實(shí)驗(yàn)結(jié)果證明，急性心肌肥厚的嚙齒類動(dòng)物心肌細(xì)胞沒有再一次進(jìn)入細(xì)胞周期、合成DNA并進(jìn)行有絲分裂的能力。這些發(fā)現(xiàn)都證明了一個(gè)學(xué)說(shuō)，在出生后不久，心室肌細(xì)胞就永久的不再進(jìn)入細(xì)胞周期并注定不再?gòu)?fù)制最終細(xì)胞死亡。在20世紀(jì)50年代中期這種論點(diǎn)被LINZBACH在形態(tài)學(xué)研究中的成果所質(zhì)疑。形態(tài)學(xué)研究表明在心衰患者的心肌中有發(fā)現(xiàn)心肌細(xì)胞增生。最近的數(shù)據(jù)結(jié)果支持LINZBACH的假說(shuō)，并確認(rèn)在人類心臟失代償期，心室肌細(xì)胞的數(shù)量幾乎增加了一倍（4，20，21）。定量分析未能成功記載心肌細(xì)胞的有絲分裂，更偏向于應(yīng)用體視學(xué)定律分析心肌細(xì)胞數(shù)量上的變化。缺乏有絲分裂使得對(duì)心肌細(xì)胞分化機(jī)制的解釋更加復(fù)雜，其中包括心肌細(xì)胞的縱向分裂而細(xì)胞核卻不分裂。這種現(xiàn)象將導(dǎo)致在每個(gè)細(xì)胞中細(xì)胞核含量的減少。然而在人類心臟中單核細(xì)胞與雙核細(xì)胞的比例是不變的。如果細(xì)胞沒有完成最終分裂，在細(xì)胞處于G0期時(shí)，給予細(xì)胞一定刺激，細(xì)胞將再次進(jìn)入細(xì)胞周期完成細(xì)胞核及細(xì)胞質(zhì)的分裂。只有這種增長(zhǎng)方式才會(huì)出現(xiàn)心肌細(xì)胞數(shù)量的增長(zhǎng)與心肌細(xì)胞的再生。早期的發(fā)現(xiàn)及近期的數(shù)據(jù)都堅(jiān)持了這種增值方式的可能性，因?yàn)樵谛牧λソ叩男呐K心機(jī)中已經(jīng)被證實(shí)存在細(xì)胞核與細(xì)胞質(zhì)的分裂。心肌細(xì)胞增殖心肌細(xì)胞增殖根據(jù)學(xué)說(shuō)中提到，心室肌細(xì)胞是一種沒有再生能力的細(xì)胞，細(xì)胞壽命完全與個(gè)體或生物的壽命相對(duì)應(yīng)。在人類試驗(yàn)研究中證實(shí)，在人類出生幾個(gè)月后心肌細(xì)胞數(shù)量就已達(dá)到成人水平，他們一直以每分鐘70次的頻率收縮，直到細(xì)胞死亡。由于有一部分人口壽命能達(dá)到100歲或是更長(zhǎng)，一個(gè)不可避免的結(jié)論由此產(chǎn)生心肌細(xì)胞在功能與形態(tài)上可能是不朽的。這種假說(shuō)與細(xì)胞衰老、細(xì)胞程序化死亡及隨著哺乳動(dòng)物心臟的衰老，細(xì)胞翻新速度減慢的邏輯產(chǎn)生矛盾。然而后者的可能性更大，在沒有疾病的正常心臟發(fā)現(xiàn)，從17歲到89歲，心肌細(xì)胞每年將減少64106個(gè)，這暗示了細(xì)胞是隨診年齡增長(zhǎng)死亡的。除此之外，盡管缺少生理負(fù)荷需求，心肌細(xì)胞也可以再進(jìn)入細(xì)胞周期，合成DNA。那些對(duì)與心臟細(xì)胞衰老及心肌細(xì)胞不斷更新的研究表明，在正常情況下，每100萬(wàn)個(gè)心肌細(xì)胞中有14個(gè)細(xì)胞能進(jìn)行有絲分裂。在衰竭的心肌中，心肌細(xì)胞這種再生與代替死亡細(xì)胞的能力明顯增強(qiáng)，每100

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簡(jiǎn)介：中文中文3200字出處出處ICHIKAWAT,ERTURKSM,MOTOSUGIU,ETALHIGHBVALUEDIFFUSIONWEIGHTEDMRIINCOLORECTALCANCERJAMERICANJOURNALOFROENTGENOLOGY,2006,1871181184高B值彌散加權(quán)值彌散加權(quán)MRIMRI在結(jié)直腸癌中的應(yīng)用在結(jié)直腸癌中的應(yīng)用ICHIKAWAT,ERTURKSM,MOTOSUGIU,ETAL摘要摘要目的目的這篇文章的目的是評(píng)估高B值擴(kuò)散加權(quán)成像（DWMRI）檢測(cè)大腸腺癌的實(shí)用性。結(jié)論結(jié)論高B值DWMRI在檢測(cè)大腸腺癌方面具有很高的靈敏度和特異性檢測(cè)。關(guān)鍵詞癌癥；結(jié)腸；彌散加權(quán)成像；磁共振前言彌散加權(quán)MRI（DWMRI），在評(píng)估的惡性腫瘤變得越來(lái)越重要。人們普遍接受DW核磁共振成像是在使生物組織的非侵入性的特性基礎(chǔ)上，反映它們的水?dāng)U散性征，它能提供組織生物物理性質(zhì)方面的信息，如細(xì)胞的組織和密度，顯微組織及微循環(huán)。DW核磁共振成像已被廣泛用于在影像學(xué)，但其腹部?jī)?nèi)的應(yīng)用卻受到大的生理運(yùn)動(dòng)的阻礙，如呼吸，腸蠕動(dòng)，血流量，及比擴(kuò)散更大的振幅等。高原直泰等提出了DWMRI的技術(shù)可能提供改進(jìn)的信號(hào)噪聲比（信噪比）的圖像，這些圖像的對(duì)比度，在黑色和白色圖像對(duì)比度特性密切類似PET逆轉(zhuǎn)。我們猜測(cè)，由于不同的健康和腫瘤組織的細(xì)胞結(jié)構(gòu)的不同，高B值DWMRI圖像，可以直接用于腫瘤的檢測(cè)。我們決定研究大腸腺癌，因?yàn)榻Y(jié)腸MRI有一定的挑戰(zhàn)，包括非實(shí)體性質(zhì)的器官，胃腸蠕動(dòng)，和運(yùn)動(dòng)腔內(nèi)的內(nèi)容物的干擾等。因此，我們?cè)谶@個(gè)初步研究的目的是評(píng)估的有用的高B值DWMRI檢測(cè)大腸腺癌。材料及方法材料及方法患者患者2004年8月至2005年2月，為期6個(gè)月期間內(nèi)，在我們的機(jī)構(gòu)和兩個(gè)相關(guān)的醫(yī)院中共收集了33例患者（平均年齡59歲，范圍3369歲，15名女性，18名男性），并納入本研究。其中33例均經(jīng)結(jié)腸內(nèi)窺鏡證實(shí)大腸癌，病灶從20毫米到70毫米不等（平均33毫米）被發(fā)現(xiàn)在，病變位于直腸（14例），乙狀結(jié)腸（8例），橫結(jié)腸（N2），升結(jié)腸（8例），盲腸（1例）。另外選取同一時(shí)期15名結(jié)腸鏡檢為陰性的患者作為對(duì)照。所有大腸癌患者手術(shù)切除并證實(shí)診斷。所有患者和陰性對(duì)照組的病例在檢查前均行增強(qiáng)CT及MR。本研究施行前已經(jīng)我們的機(jī)構(gòu)審查委員會(huì)批準(zhǔn)且所有患者簽署知情同意書。MRIMRI序列及參數(shù)序列及參數(shù)研究為何高B值DWMR圖像上只有結(jié)腸腺癌，表現(xiàn)出強(qiáng)烈的信號(hào)強(qiáng)度，而健康的結(jié)腸則不是高信號(hào)的原因是一個(gè)具有挑戰(zhàn)性的問題，值得進(jìn)一步研究。然而，理論解釋可能構(gòu)造通過(guò)DW核磁共振成像良好的一般的假設(shè)。這是眾所周知的，擴(kuò)散即隨機(jī)的平移分子運(yùn)動(dòng)，也被稱為布朗運(yùn)動(dòng)。DWMRI是唯一的成像方法，該方法可以評(píng)估在體內(nèi)的擴(kuò)散過(guò)程。在細(xì)胞外和細(xì)胞內(nèi)的組件的組織的水分子的擴(kuò)散速度是不同的。細(xì)胞內(nèi)成分的擴(kuò)散速度相對(duì)較慢，這是因?yàn)榇嬖诩?xì)胞膜。因此，表觀擴(kuò)散系數(shù)（ADC），這是定量表達(dá)的組織中的擴(kuò)散特性，與胞外和胞內(nèi)組分的比例。他們往往會(huì)減少與增加組織細(xì)胞性或細(xì)胞密度。相反，細(xì)胞密度可能是腫瘤惡化的指標(biāo)LYNG以等報(bào)道腫瘤細(xì)胞高轉(zhuǎn)移能力增加。此外，在除了細(xì)胞膜，細(xì)胞內(nèi)的細(xì)胞骨架，細(xì)胞器，基質(zhì)型纖維和可溶性大分子在腫瘤的擴(kuò)散也限制。因此，擴(kuò)散的曲線迅速衰減或大型ADC值可能是典型的外大空間和小細(xì)胞性健康組織或良性的病理過(guò)程，而曲線衰減慢或小的ADC值可能表示惡性腫瘤或細(xì)胞過(guò)多。因此，DWMRI應(yīng)該可以敏感的鑒別病理組織特性。事實(shí)上，一些報(bào)道已經(jīng)指出各種惡性病變ADC值下降。然而，以前相關(guān)DWMR的研究并沒有直接視覺評(píng)估和報(bào)告這種技術(shù)的腹部病癥的診斷性能。雖然在本研究中所使用的技術(shù)主要基于DW核磁共振成像，事實(shí)上，DW核磁共振成像并沒有被經(jīng)常使用在臨床設(shè)置用于檢測(cè)大腸癌，但作為一個(gè)潛在的工具，用于治療監(jiān)測(cè)手段曾被提出過(guò)，建議使用的應(yīng)用程序是非定性得，但定量基于ADC測(cè)量。我們?cè)谶@項(xiàng)研究中使用的高B值DWMRI技術(shù)與多個(gè)激勵(lì)和使用收購(gòu)法無(wú)屏氣，提高信噪比。因?yàn)槠翚鈷呙钑r(shí)間的限制，不允許獲得足夠的SNR和多個(gè)激發(fā)，就不可以用來(lái)獲得作為多平面重建源圖像的彌散加權(quán)的薄層圖像。相反，運(yùn)動(dòng)偽影的增加是可能存在的理論缺點(diǎn)，然而，在實(shí)踐中，被平均的運(yùn)動(dòng)偽影期間多次激發(fā)的應(yīng)用使DW核磁共振成像和重建圖像變得不顯眼的運(yùn)動(dòng)探測(cè)梯度。因此，圖像有更好的信噪比都達(dá)到了絕對(duì)變得無(wú)法計(jì)算，因?yàn)樾盘?hào)平均ADC值交換。我們的初步結(jié)果證明，高B值DWMRI對(duì)于檢測(cè)大腸癌的診斷表現(xiàn)為高靈敏度，30/33（91％）和特異性（100％，15/15），這種技術(shù)的其他優(yōu)點(diǎn)是，它是完全非侵襲性的，并不需要暴露于電離輻射或注入造影材料，并且不會(huì)引起病人的不適。此外，因?yàn)樗莵?lái)自行之有效的DWMRI技術(shù)，高B值DWMRI并不需要運(yùn)營(yíng)商提供先進(jìn)的技術(shù)技能或高成本的基礎(chǔ)設(shè)施投資，如回旋加速器PET等。高B值DWMRI的另一個(gè)優(yōu)點(diǎn)是，它是一個(gè)可以很容易地添加到MR檢查序列，因?yàn)樗恍枰粋€(gè)很短的掃描時(shí)間。在本研究中，我們沒有評(píng)估淋巴結(jié)轉(zhuǎn)移，我們的目的是評(píng)估高B值DWMRI檢測(cè)大腸腺癌的診斷能力。然而，在一些患者中，淋巴結(jié)在圖像上可以顯示?；谖覀兒?jiǎn)短的影像學(xué)病理的相關(guān)性，大部分轉(zhuǎn)移淋巴結(jié)表現(xiàn)為高信號(hào)強(qiáng)度，所以可以被很好的檢測(cè)，但在一些患者健康的淋巴結(jié)也同樣顯示出很高的信號(hào)強(qiáng)度。關(guān)于特異性檢測(cè)淋巴結(jié)轉(zhuǎn)移，這種觀察可能是一個(gè)具有挑戰(zhàn)性的問題，有待進(jìn)一步研究。我們的研究有一定的局限性。首先，研究人口相對(duì)較少，我們的研究結(jié)果需要在更大范圍的臨床研究證實(shí)。其次，研究包括陰性的病例，但不包括其他良性疾病，如發(fā)炎性腸道疾病或良性腫瘤。因此，應(yīng)考慮在本研究中報(bào)道的靈敏度是相對(duì)的而不是絕對(duì)的?？傊?，根據(jù)我們的初步研究結(jié)果，高B值DWMRI可能是一個(gè)檢測(cè)大腸癌有用的工具，它顯示了較高的敏感性和特異性。然而，因?yàn)橐陨纤枋龅木窒扌裕孕枰M(jìn)一步的大樣本研究來(lái)支持我們的調(diào)查結(jié)果。

簡(jiǎn)介：中文中文4900字出處出處RUSCAN,MONTICELLISMIR146AINIMMUNITYANDDISEASEJMOLECULARBIOLOGYINTERNATIONAL,2011,17免疫和疾病中的免疫和疾病中的MIR146MIRNA分子是一類在細(xì)胞中可以影響各種生物功能的分子。已經(jīng)證實(shí)他們與癌癥、病毒感染和免疫性疾病相關(guān)，近些年，還發(fā)現(xiàn)它們成為免疫反應(yīng)的重要調(diào)節(jié)者。尤其是MIR146A迅速成為一種重要的分化調(diào)節(jié)者，同樣在先天免疫和獲得性免疫中有很重要的作用。鑒于它在調(diào)節(jié)細(xì)胞功能方面的重要作用，MIRNA146A在各種腫瘤中被發(fā)現(xiàn)表達(dá)失調(diào)也不足為奇。這篇文章，我們主要總結(jié)了近些年對(duì)MIR146A在先天免疫和獲得性免疫反應(yīng)及疾病中的作用的進(jìn)展。1介紹介紹MIRNA代表了所有的細(xì)胞的普遍特征，因?yàn)樗鼈冋{(diào)節(jié)了細(xì)胞轉(zhuǎn)錄過(guò)程中的大部分。至今，672個(gè)鼠的MIRNA分子和1048個(gè)人的MIRNA已經(jīng)在MIRBASE數(shù)據(jù)庫(kù)中被描述（HTTP//WWWMIRBASEORG/,RELEASESEPT2010其中每個(gè)MIRNA潛在地調(diào)節(jié)了成百上千的目標(biāo)基因，這顯著地?cái)U(kuò)展了調(diào)節(jié)模式。然而一些MIRNA表達(dá)廣泛，其他的僅僅抑制有限發(fā)展的階段、組織或者細(xì)胞特異的類型。類似于一些哺乳細(xì)胞的類型，細(xì)胞免疫系統(tǒng)依賴MIRNA來(lái)調(diào)節(jié)譜系的定型、增殖、遷移和分化。在大部分的情況下，這些活動(dòng)都是十分和諧，在廣泛的表達(dá)和細(xì)胞特定的MIRNA類型方面。當(dāng)MIRNA的表達(dá)被改變時(shí)MIRNA在調(diào)節(jié)分化和免疫細(xì)胞功能方面的重要性就通過(guò)表型干擾表現(xiàn)得尤為突出。MIRNA在修飾免疫反應(yīng)的重要作用，可能任何MIRNA表達(dá)的失調(diào)都會(huì)導(dǎo)致自身免疫性疾病、慢性炎癥和惡性腫瘤的發(fā)生。事實(shí)上，已經(jīng)證明人類的一些疾病和MIRNA的表達(dá)失調(diào)有關(guān)，MIRNA的功能可以充當(dāng)癌基因和抑癌基因。MIR146A最近已經(jīng)報(bào)道成為在先天和獲得性免疫中重要的細(xì)胞分化和功能的調(diào)節(jié)者。在此，我們總結(jié)了近來(lái)關(guān)于MIR146A在免疫反應(yīng)和疾病中作用的理解（見表1）。2什么是什么是MIRNA（此部分未翻譯，和之前的文章基本重復(fù)）（此部分未翻譯，和之前的文章基本重復(fù)）MIRNA是一種非編碼小RNA分子（長(zhǎng)度2025核苷酸），參與轉(zhuǎn)錄后基因的調(diào)控。它們最初為初級(jí)MIRNAPREMIRNA，這會(huì)在細(xì)胞核內(nèi)通過(guò)微處理復(fù)合體形成前體發(fā)夾結(jié)構(gòu)（PREMIRNA），這種復(fù)合體發(fā)函RNASEIII酶DROSHA。3MIRNA146A在獲得性免疫反應(yīng)中在獲得性免疫反應(yīng)中雖然獲得性免疫應(yīng)答反應(yīng)失調(diào)會(huì)導(dǎo)致自身免疫性疾病和慢性炎癥疾病，但是能有效地消滅病原體的感染。獲得性免疫反應(yīng)的發(fā)展和進(jìn)步對(duì)于侵入的病原體會(huì)形成一系列精密的反應(yīng)步驟，包括免疫細(xì)胞的活化增殖和隨后遷移到炎癥部位。最初的跡象表明MIRNA參與調(diào)節(jié)免疫細(xì)胞的分化，這已經(jīng)被陳和他的同事們用MIR181在造血干細(xì)胞中特異性的表達(dá)證明。在造血干細(xì)胞中的易位表達(dá)導(dǎo)致了部分B細(xì)胞系在體外誘導(dǎo)分化和大鼠的模型中的增加。接下來(lái)的開創(chuàng)性的研究，證明MIRNA是控制免疫細(xì)胞分化和功能重要的組成部分。當(dāng)與抗原結(jié)合后，原始CD4T細(xì)胞升高了T細(xì)胞亞群（TH1，TH2，TH17，TREGS，濾泡輔助性T細(xì)胞）根據(jù)它們各自在宿主防御中的功能。最初的表達(dá)鑒定了MIRNA的表達(dá)譜在不同的T細(xì)胞亞群和部分分化階段。T細(xì)胞特異性切酶顯示在T細(xì)胞的發(fā)展中需要MIRNA通路，同時(shí)T細(xì)胞亞群的分化也需要。事實(shí)上，缺乏DICER酶的T細(xì)胞表現(xiàn)出向TH1亞群的分化增加，同時(shí)向TH2減少。根據(jù)復(fù)雜的基因調(diào)控網(wǎng)絡(luò)，增殖的T細(xì)胞比靜止的T細(xì)胞表達(dá)更短的3‘UTR，使得這些MRNA更不易被MIRNA調(diào)控由于缺失MIRNA結(jié)合位點(diǎn)。最終，個(gè)別的MIRNA對(duì)T細(xì)胞分化和功能有重要的作用。例如，MIR181A，面對(duì)病毒的入侵時(shí)免疫細(xì)胞使用各個(gè)層次的負(fù)向調(diào)節(jié)以防免疫應(yīng)答不受控制，這種調(diào)節(jié)機(jī)制也可以被病毒使用為了逃離免疫監(jiān)視。發(fā)現(xiàn)MIR146A在調(diào)節(jié)皰疹性口腔炎病毒（VSV）的感染時(shí)有作用。在巨噬細(xì)胞中，VSV的感染上調(diào)了MIR146A的表達(dá)，導(dǎo)致負(fù)向調(diào)節(jié)VSV觸發(fā)的I型IFN通過(guò)下調(diào)TRAF6，IRAK1和IRAK2，因此促進(jìn)了VSV在巨噬細(xì)胞中的復(fù)制。作者提出了一種模式，VSV的感染首先被RIGI（視黃酸誘導(dǎo)基因蛋白I）感受到，這反過(guò)來(lái)抑制I型IFN的產(chǎn)生來(lái)對(duì)抗VSV的感染。同時(shí)，VSV的感染上調(diào)了MIR146A的表達(dá)，通過(guò)破壞RIGI信號(hào)抑制了先天免疫應(yīng)答。EBV（人類皰疹病毒4）感染過(guò)超過(guò)90的全世界的人口。EV病毒感染會(huì)導(dǎo)致惡性腫瘤，包括BURKITT’S和霍奇金淋巴瘤。LMP1潛伏膜蛋白是EV病毒編碼的主要的癌基因產(chǎn)物，它可以活化轉(zhuǎn)錄因子如NFKB和AP1，由此來(lái)控制宿主細(xì)胞、調(diào)節(jié)細(xì)胞分化、遷移和凋亡的過(guò)程。通過(guò)它的這種活化轉(zhuǎn)錄因子的能力，LMP1也能誘導(dǎo)細(xì)胞中MIRNA的表達(dá)，其中最顯著的是MIR146A，因此在感染EB病毒后對(duì)細(xì)胞的永生化和腫瘤發(fā)生有幫助。6MIR146和癌癥和癌癥癌癥是一系列復(fù)雜過(guò)程的結(jié)果，是一些基因各種順序改變的積累，包括編碼MIRNA。既然MIRNA參與保持基因平衡的任務(wù)，那么它也可以決定細(xì)胞的命運(yùn)，它們的失調(diào)潛在地會(huì)減弱這種平衡，因此可能導(dǎo)致癌癥的發(fā)生、發(fā)展。事實(shí)上，MIRNA表達(dá)譜中已經(jīng)發(fā)現(xiàn)在一些癌癥中MIRNA的表達(dá)被顯著地改變了。關(guān)于MIR146A可能參與癌癥發(fā)展的初步證據(jù)來(lái)自MIR146A在PTC（甲狀腺乳頭狀癌）樣本中被上調(diào)的研究與未受影響的甲狀腺組織相比。有趣的是，一組5個(gè)MIRNA，包括MIR221，MIR222，MIR146對(duì)區(qū)分PTC和正常甲狀腺組織是足夠的了。在免疫設(shè)置中進(jìn)行同樣的觀察，MIR146A/B在代謝旺盛的人類乳腺癌細(xì)胞株MDAMB231中的過(guò)表達(dá)顯著下調(diào)了IRAK1和TRAF6的表達(dá)，負(fù)調(diào)節(jié)了NFKB的活性。在功能上，這導(dǎo)致與控制組的細(xì)胞相比這些細(xì)胞的侵襲和轉(zhuǎn)移的能力明顯受損。這些發(fā)現(xiàn)說(shuō)明MIR146在乳腺癌細(xì)胞中不僅是NFKB的負(fù)向調(diào)節(jié)者，而且說(shuō)明調(diào)節(jié)MIR146的水平或許可以潛在地抑制乳腺癌的轉(zhuǎn)移。用相同的路線，在眾多的MIRNA中發(fā)現(xiàn)與正常宮頸組織相比MIR146A在宮頸癌組織中上調(diào)。當(dāng)引入細(xì)胞株時(shí)，發(fā)現(xiàn)MIR146A促進(jìn)了細(xì)胞增殖。雖然這種增加增殖的分子機(jī)制已經(jīng)被研究，但是這些發(fā)現(xiàn)說(shuō)明MIR146A可能與宮頸癌的發(fā)生有關(guān)。另一種癌癥激素難治性前列腺癌（HRPC），MIR146A的水平減少了，與雄激素敏感性的非癌癥上皮細(xì)胞相比。在這方面，MIR146A扮演腫瘤抑制的角色，減少了它的靶點(diǎn)ROCK1的水平，ROCK1是參與HRPC轉(zhuǎn)化的一個(gè)關(guān)鍵激酶。因此，強(qiáng)化MIR146A的表達(dá)可以減少ROCK1蛋白的水平、細(xì)胞分化、侵襲和向人單層骨髓上皮細(xì)胞的轉(zhuǎn)移。同樣，MIR146A在胰腺癌細(xì)胞中水平較低與正常人胰腺細(xì)胞相比。MIR146A的表達(dá)通過(guò)下調(diào)EGFR（表皮生長(zhǎng)因子受體）和IRAK1抑制了胰腺癌細(xì)胞的侵襲能力。最后，最近的一項(xiàng)研究說(shuō)明用DZ（二氮嗪）治療骨髓源性的間充質(zhì)肝細(xì)胞（MSCS）顯著地增加了MIR146A的表達(dá)，促進(jìn)了細(xì)胞的存活。此外，通過(guò)反義抑制劑MIR146A水平的下調(diào)消除了DZ誘導(dǎo)的細(xì)胞保護(hù)作用。這說(shuō)明MIR146A在MSC（骨髓基質(zhì)細(xì)胞）存活中有重要作用。7基因多態(tài)性和轉(zhuǎn)錄后的修飾基因多態(tài)性和轉(zhuǎn)錄后的修飾基因多態(tài)性影響MIRNA的表達(dá)、成熟或者M(jìn)RNA的識(shí)別可能對(duì)增加腫瘤的風(fēng)險(xiǎn)成為重要的決定因素。事實(shí)上，最近KIT癌基因3‘UTR遺傳變異被描述，這導(dǎo)致了MIR221種子區(qū)的不匹配，伴隨增加黑色素瘤的風(fēng)險(xiǎn)。至于MIR146A，單核苷酸多態(tài)性在前MIR146A的傳遞鏈上被發(fā)現(xiàn)。罕見的C等位基因降低了和前體MIR146A合成的過(guò)程，降低了PREMIR146A和成熟MIR146A的水平，解鎖了它的靶基因，包括TRAF6和IRAK1。一項(xiàng)與PTC患者有關(guān)的研究，GC雜合狀態(tài)會(huì)增加獲得性PTC的風(fēng)險(xiǎn)，但是兩個(gè)純合子狀態(tài)

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