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简介：AbstractImportance:Cadherin-11 (CDH11), a cell-to-cell adhesion molecule, is implicated in the fibrotic process of several organs. Biliary atresia (BA) is a common cholestatic liver disease featuring cholestasis and progressive liver fibrosis in children. Cholestatic liver fibrosis may progress to liver cirrhosis and lacks effective therapeutic strategies. Currently, the role of CDH11 in cholestatic liver fibrosis remains unclear.Objective:This study aimed to explore the functions of CDH11 in cholestatic liver fibrosis.Methods:The expression of CDH11 in BA livers was evaluated by database analysis and immunostaining. Seven BA liver samples were used for immunostaining. The wild type (Wt) and CDH11 knockout (CDH11-/-) mice were subjected to bile duct ligation (BDL) to induce cholestatic liver fibrosis. The serum biochemical analysis, liver histology, and western blotting were used to assess the extent of liver injury and fibrosis as well as activation of transforming growth factor-β (TGF-β)/Smad pathway. The effect of CDH11 on the activation of hepatic stellate cell line LX-2 cells was investigated.Results:Analysis of public RNA-seq datasets showed that CDH11 expression levels were significantly increased in livers of BA, and CDH11 was correlated with liver fibrosis in BA. BDL-induced liver injury and liver fibrosis were attenuated in CDH11-/- mice compared to Wt mice. The protein expression levels of phosphorylated Smad2/3 were decreased in livers of CDH11-/- BDL mice compared to Wt BDL mice. CDH11 knockdown inhibited the activation of LX-2 cells.Interpretation:CDH11 plays an important role in cholestatic liver fibrosis and may represent a potential therapeutic target for cholestatic liver disease, such as BA.

简介：Anewthermokineticreducedextentmethodforstudyingofthereversiblecompetitiveinhibitionofsinglesubstrateenzyme-catalyzedreactionswasproposedinthispaper.Thereactionthatarginase-catalyzedhydrolysisofL-argininetoL-ornithineandureaandtheinhibitionofthisreactionbytheproduct,L-ornithine,andexogenousL-lysinewerestudiedat37℃in40mmol·L^-1sodiumbarbiturate-HC1buffersolution(pH=9.4).MichealisconstantKmforarginineandmaximumvelocityVmofthereactionweredeterminedtobe5.14mmol·L^-1and1.13×10^-2mmol·L^+1·s^-1,respectively.TheproductinhibitionconstantKpandinhibitoryconstantK1ofL-lysineweredeterminedtobe1.18and5.6mmol.L-l,respectively.Alltheresultshavebetterrepeatabilityandself-consistencyandareinagreementwithliteraturevalues.Thisnewmethodusingmoredirectthermalinformationfromtheprocesswouldgivemorereliablekineticinformationthanthetraditionalinitialratemethod.

简介：SulfatechitosanderivativeshavegoodsolubilityandtherapeuticeffectonthecellmodelofNAFLD.TheaimofthisstudywastoexaminethetherapeuticeffectofsulfatechitosanderivativesonNAFLD.ThemaleWistarratswereorallyfedhighfatemulsionandreceivedsulfatechitosanderivativesfor5weekstodeterminethepre-treatmenteffectofsulfatechitosanderivativesonNAFLD.ToevaluatethetherapeuticeffectofsulfatechitosanderivativesonNAFLD,theratswereorallyfedwithhighconcentrationemulsionfor5weeks,followedbysulfatechitosanderivativesfor3weeks.Histologicalanalysisandbiomedicalassaysshowedthatsulfatechitosanderivativescandramaticallypreventthedevelopmentofhepaticsteatosisinhepatocytecells.Inanimalstudies,pre-treatmentandtreatmentwithsulfatechitosanderivativessignificantlyprotectedagainsthepaticsteatohepatitisinducedbyhighfatdietaccordingtohistologicalanalysis.Furthermore,increasedTC,ALT,MDA,andLEPinNAFLDweresignificantlyamelioratedbypre-treatmentandtreatmentwithsulfatechitosanderivatives.Furthermore,increasedTG,AST,andTNF-αinNAFLDweresignificantlyamelioratedbytreatmentwithsulfatechitosanderivatives.Sulfatechitosanderivativeshavegoodpre-treatmentandtherapeuticeffectonNAFLD.

简介：Themammalianliverhasaverystrongregenerationcapacityafterpartialhepatectomy(PH).Tofurtherlearnthegenesparticipatingintheliverregeneration(LR),551cDNAsselectedfromsubtractedcDNAlibrariesoftheregeneratingratliverwerescreenedbymicroarray,andtheirexpressionprofileswerestudiedbyclusterandgeneralizationanalyses.Amongthem,177geneswereidentifiedunreportedandup-ordown-regulatedmorethantwofoldatoneormoretimepointsafterPH,ofwhich62genesweredown-regulatedtolessthan0.5;99geneswereup-regulatedto2-10folds,and16geneswereeitherup-ordown-regulatedatdifferenttimepointsduringLR.ByusingBLASTandGENSCAN,thesegeneswerelocatedonresponsiblechromosomeswith131genesonthelongarmsofthechromosomes.Theclusterandgeneralizationanalysesshowedthatthegeneexpressionprofilesaresimilarin2and4,12and16,96and144hrespectivelyafterPH,suggestingthattheactionsofthegenesexpressedinthesameprofilesaresimilar,andthoseexpressedindifferentprofileshavelesssimilarity.However,thetypes,characteristicsandfunctionsofthe177genesremaintobefurtherstudied.

简介：背景：为疼痛地势的Opioid药方正在增加。Codeine是在几个欧洲国家的统治opioid，与在最高的codeine用户之中的挪威。瞄准：决定codeine是否首先为剧烈疼痛被使用或是否有一个药方模式，显示有问题的opioid使用。方法：在挪威的所有药店被强迫在所有分配药方上在公共健康的挪威的研究所电子地提交数据到挪威的药方数据库。因为所有药方与一个独特的人标识符被识别，识别所有药方到一个题目是可能的。codeine的有的药方在2004，2005或2006分配了到他们的所有题目在学习被包括。结果：385190个挪威的人有在2005由于非癌症疼痛分配到他们的codeine的至少一张药方，相应于8.3%的1年的周期的流行。223(58%)778在2005收到了仅仅一张药方，121(31%)025收到了超过一张药方，但是<120定义每日的剂量(DDD)，30(8%)939在120和365DDD之间收到了，7661(2%)在365和730DDD之间，当(0.5%)仅仅1787超过了730DDD的最大的推荐剂量时。在后者组，有benzodiazepines(65%)和carisoprodol(45%)的合作药是流行的。结论：大约一在在挪威的10个成年的人是在2005的分配codeine。一个多数(58%)收到了codeine仅仅一次，为剧烈疼痛最可能，而一个小少数(0.5%)有一个药方模式显示有问题的opioid，使用。

简介：Splanchniccirculationistheprimarymechanismthatregulatesvolumesofcirculatingbloodandsystemicbloodpressureinpatientswithcirrhosisaccompaniedbyportalhypertension.Recently,interesthasbeenexpressedinmodulatingsplanchniccirculationinpatientswithlivercirrhosis,becausethiscapabilitymightproducebeneficialeffectsincirrhoticpatientsundergoingalivertransplant.Pharmacologicmodulationofsplanchniccirculationbyuseofvasoconstrictorsmightminimizevenouscongestion,replenishcentralbloodflow,andthusoptimizemanagementofbloodvolumeduringalivertransplantoperation.Moreover,splanchnicmodulationminimizesanyhighportalbloodflowthatmayoccurfollowingliverresectionandthesubsequentlivertransplant.Thiseffectissignificant,becausehighportalflowimpairsliverregeneration,andthusadverselyaffectsthepostoperativerecoveryofatransplantpatient.Anincreaseinportalbloodflowcanbeminimizedbyeithersurgicalmethods（e.g.,splenicarteryligation,splenectomyorportocavalshunting）oradministrationofsplanchnicvasoconstrictordrugssuchasVasopressinorterlipressin.Finally,modulationofsplanchniccirculationcanhelpmaintainperioperativerenalfunction.Splanchnicvasoconstrictorssuchasterlipressinmayhelpprotectagainstacutekidneyinjuryinpatientsundergoinglivertransplantationbyreducingportalpressureandtheseverityofahyperdynamicstate.Theseeffectsareespeciallyimportantinpatientswhoreceiveatoosmallforsizegraft.TerlipressinselectivelystimulatesV1receptors,andthuscausesarteriolarvasoconstrictioninthesplanchnicregion,withaconsequentshiftofbloodfromsplanchnictosystemiccirculation.Asaresult,terlipressinenhancesrenalperfusionbyincreasingbotheffectivebloodvolumeandmeanarterialpressure.

简介：PolyomavirusBK（BKV）infectsupto90%ofthegeneralpopulation.Afterprimaryinfection,occurringearlyduringchildhood,astateofnon-replicativeinfectionisestablishedinthereno-urinarytract,withoutcomplicationsforimmunocompetenthosts.Inimmunocompromisedindividuals,particularlytransplantedpatients,asymptomaticBKVviremiaand/orviruriacanbeobserved.RenalgraftsmayalsobesourcesofinfectionasBKVpreferskidneysratherthanothersolidorgansfortransplantationsuchastheliver.ThemechanismbehindthehigherincidenceofBKVinfectioninkidneytransplantpatients,comparedtoliverorhearttransplantation,isunclearandtheprevalenceofBKVinfectioninnon-renalsolidorgantransplantshasnotbeenyetthoroughlyinvestigated.WeevaluatedtheprevalenceofPolyomavirusBKinfectionamonglivertransplantrecipients.APubMedsearchwasconductedusingthetermsBKVinfectionANDlivertransplantrecipients;BKVANDnon-renalsolidorgantransplant＊;BKVinfectionANDimmunosuppression;thesearchwaslimitedtotitle/abstractandEnglish-languagearticlespublishedfrom2000,toMarch2015.ElevenrelevantstudiessuggestthattheprevalenceofBKVviruriaand/orviremiaamonglivertransplantrecipientsislessthanthatreportedinkidneyorhearttransplantrecipients,exceptwhenchronickidneydisease（CKD）ispresentatthesametime.DataalsosuggestthatviruricandviremicpatientshavehigherlevelsofserumcreatininethanBKVnegativepatients.Moreover,nospecificimmunosuppressivedrugsareassociatedwiththeonsetofBKVnephropathy.ThecomorbidityoftransplantationandCKDcouldplayamajorroleinpromotingBKVreplication.

简介：Livercancer,primarilyhepatocellularcarcinoma(HCC),isamajorcauseofcancer-relateddeathworldwide.HCCisasuitablemodelofinflammation-inducedcancerbecausemorethan90%ofHCCcasesarecausedbyliverdamageandchronicinflammation.Severalinflammatoryresponsepathways,suchasNF-κBandJAK/STAT3signalingpathways,playrolesinthecrosstalkbetweeninflammationandHCC.MicroRNAs(miRNAs)areevolutionarilyconserved,shortendogenous,non-codingsingle-strandedRNAsthatareinvolvedinvariousbiologicalandpathologicalprocessesbyregulatinggeneexpressionandproteintranslation.EvidenceshowedthatmiRNAsplayapivotalroleinhepatitisvirusinfectionandserveaspromotersorinhibitorsofinflammatoryresponse.AberrantmiRNAwasobservedduringliverinflammationandHCC.ManydysregulatedmiRNAsmodulatetheinitiationandprogressionofinflammation-inducedHCC.ThisreviewsummarizestheroleandfunctionsofmiRNAsininflammation-associatedHCC,aswellasthedesignedtherapeuticstargetingmiRNAstotreatliverinflammationandHCC.

简介：AIM:Tostudytheformationofintracellularglyceraldehyde-derivedadvancedglycationendproducts(Glycer-AGEs)inthepresenceofhighconcentrationsoffructose.METHODS:CellsofthehumanhepatocytecelllineHep3Bwereincubatedwithorwithoutfructoseforfivedays,andthecorrespondingcelllysateswereseparatedbytwo-dimensionalgradientsodiumdodecylsulfate-polyacrylamidegelelectrophoresis.Glycer-AGEsweredetectedwiththeanti-Glycer-AGEsantibody.Furthermore,theidentificationoftheproteinsthataremodifiedbyglyceraldehydeinthepresenceofhighconcentrationsoffructosewasconductedusingmatrixassistedlaserdesorption/ionizationtime-of-flightmassspectrometry(MALDI-TOF-MS).TheproteinandmRNAlevelsweredeterminedbyWesternblottingandrealtimereversetranscriptionPCR,respectively.RESULTS:Theresultsofthetwo-dimensionalgradientsodiumdodecylsulfate-polyacrylamidegelelectrophoresisindicatedagreateramountofGlycerAGEsinthesampleexposedtohighconcentrationsoffructosethaninthecontrol.ThedetectedGlycerAGEsshowedisoelectricpointsintherangeof8.0-9.0andmolecularweightsintherangeof60-80kDa.TheheterogeneousnuclearribonucleoproteinM(hnRNPM),whichplaysanimportantroleinregulatinggeneexpressionbyprocessingheterogeneousnuclearRNAstoformmaturemRNAs,wasidentifiedasamodifiedproteinusingMALDI-TOF-MS.Increasingtheconcentrationoffructoseinthemediuminducedaconcentration-dependentincreaseinthegeneratedGlycer-AGEs.Furthermore,inanexperimentusingglyceraldehyde,whichisaprecursorofGlycer-AGEs,hnRNPMwasfoundtobemoreeasilyglycatedthantheotherproteins.CONCLUSION:Theresultssuggestthatglyceraldehyde-modifiedhnRNPMaltersgeneexpression.Thischangemaycauseadverseeffectsinhepatocytesandmayserveasatargetfortherapeuticintervention.

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简介：AbstractObjective:This study aims to describe presenting characteristics of patients diagnosed with non-invasive chronic rhinosinusitis (CRS) following liver or kidney transplant and determine factors associated with disease-related complications, selection of endoscopic sinus surgery (ESS), and disease resolution in this population.Study design:Retrospective chart review.Setting:An academic tertiary care center (Mayo Clinic, Rochester, Minnesota).Subjects and methods:Liver and kidney transplant recipients evaluated by Mayo Clinic otolaryngologists for CRS between 1998 and 2018 were identified. Univariate and multivariate logistic regression analyses were used to determine patient factors and treatment modalities associated with developing complications, selection of ESS, and disease resolution.Results:Fifty-seven patients met inclusion criteria. No patients developed intraorbital or intracranial complications of their CRS. Multivariate modeling demonstrated that the presence of polyps (P = 0.036) was associated with undergoing ESS within one year of presentation. A higher Lund-Mackay (LM) computed tomography score (P = 0.023) and older age (P = 0.018) were significantly associated with decreased disease resolution. No other factors were significantly associated with the use of endoscopic sinus surgery within one year of otolaryngology presentation or resolution of CRS in this cohort.Conclusion:The risk of developing CRS-related intraorbital or intracranial complications in this immunecompromised patient cohort may be lower than originally thought. For liver- and kidney-recipients stable on immunosuppressive medication for many years, prognostic factors for CRS may mirror those for immunocompetent patients.

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简介：AbstractNon-alcoholic fatty liver disease (NAFLD) is one of the fastest-growing diseases, and its global prevalence is estimated to increase >50% by 2030. NAFLD is comorbid with metabolic syndrome, obesity, type 2 diabetes, and insulin resistance. Despite extensive research efforts, there are no pharmacologic or biological therapeutics for the treatment of NAFLD. Bile acids and sphingolipids are well-characterized signaling molecules. Over the last few decades, researchers have uncovered potential mechanisms by which bile acids and sphingolipids regulate hepatic lipid metabolism. Dysregulation of bile acid and sphingolipid metabolism has been linked to steatosis, inflammation, and fibrosis in patients with NAFLD. This clinical observation has been recapitulated in animal models, which are well-accepted by experts in the hepatology field. Recent transcriptomic and lipidomic studies also show that sphingolipids are important players in the pathogenesis of NAFLD. Moreover, the identification of bile acids as activators of sphingolipid-mediated signaling pathways established a novel theory for bile acid and sphingolipid biology. In this review, we summarize the recent advances in the understanding of bile acid and sphingolipid-mediated signaling pathways as potential contributors to NAFLD. A better understanding of the pathologic effects mediated by bile acids and sphingolipids will facilitate the development of new diagnostic and therapeutic strategies for NAFLD.

简介：Objective:LivercancerisoneofthemostcommoncancersandmajorcauseofcancerdeathsinChina,whichaccountsforover50%ofnewcasesanddeathsworldwide.Thesystematiclivercancerstatisticsincludingofprojectionthrough2030couldprovidevaluableinformationforpreventionandcontrolstrategiesinChina,andexperienceforothercountries.Methods:TheburdenoflivercancerinChinain2014wasestimatedusing339cancerregistries’dataselectedfromChineseNationalCancerCenter(NCC).Incidentcasesof22cancerregistrieswereappliedfortemporaltrendsfrom2000to2014.Theburdenoflivercancerthrough2030wasprojectedusingage-period-cohortmodel.Results:About364,800newcasesoflivercancer(268,900malesand95,900females)occurredinChina,andabout318,800livercancerdeaths(233,500malesand85,300females)in2014.WesternregionsofChinahadthehighestincidenceandmortalityrates.Incidenceandmortalityratesdecreasedbyabout2.3%and2.6%peryearduringtheperiodof2000-2014,respectively,andwoulddecreasebymorethan44%between2014and2030inChina.Theyounggeneration,particularlyforthoseagedunder40years,showedafasterdowntrend.Conclusions:Basedontheanalysis,incidenceandmortalityratesoflivercancerareexpectedtodecreasethrough2030,buttheburdenoflivercancerisstillseriousinChina,especiallyinruralandwesternareas.MostcasesoflivercancerinChinacanbepreventedthroughvaccinationandmorepreventioneffortsshouldbefocusedonhighriskgroups.

简介：AIM:Toinvestigateenoughvalidmeasurements(VMs)toassessliverfibrosisinchronichepatitisBpatients(CHB).METHODS:OnehundredandtwelveCHBpatients(25women,87men)withameanageof38.43yearsreceivedliverstiffnessevaluationsusingreal-timeshearwaveelastographyfor10VMs.Allpatientsunderwentliverbiopsy.Basedonthebiopsypathology,theliverstiffnessdataobtainedfromdifferentVMs(1,2,3,5and10times)werecomparedfortheevaluationofliverfibrosis.ThecorrelationbetweentheelasticmodulusmeansoftheliverobtainedfromdifferentVMsofdetectionateachpathologicalstagewasanalysed.Thereceiveroperatingcharacteristic(ROC)curvewasemployedtodeterminethediagnosticperformanceofdifferentVMsofdetection,andtheareasundertheROCcurveofdifferentgroupswerecompared.RESULTS:Theliverstiffnessvaluesobtainedfrom1VM,2VMs,3VMs,5VMsandall10VMsforstageF0were6.95±2.01kPa,6.87±1.83kPa,6.90±1.88kPa,6.95±1.93kPaand7.15±1.89kPa,respectively(F=0.043,P=0.996).ForstageF1,thesevalueswere7.12±1.72kPa,7.24±1.72kPa,7.21±1.74kPa,7.10±1.78kPaand7.04±1.70kPa,respectively(F=0.075,P=0.990).ForstageF2,theywere9.37±3.87kPa,9.18±3.68kPa,9.19±3.81kPa,9.18±3.81kPaand9.19±3.53kPa,respectively(F=0.012,P=1.000).ForstageF3,thesewere11.91±3.88kPa,11.78±4.04kPa,11.83±4.07kPa,11.94±4.17kPaand12.00±4.02kPa,respectively(F=0.010,P=1.000).ForstageF4,thereadingswere19.30±7.63kPa,19.40±7.36kPa,19.54±7.43kPa,19.73±7.21kPaand20.25±7.22kPa,respectively(F=0.054,P=0.995).Therewerenosignificantdifferencesbetweenthesegroups.Intraclasscorrelationcoefficientsamongdifferentpathologicalstages(F0-F4)withdifferentdetectionVMswere0.995,0.993,0.996,0.994and0.996,respectively.Themeanelasticityvaluesfrom1VM,2VMs,3VMs,5VMsand10VMscanaccuratelydistinguishfibrosisstages(F0vsF1234,F01vsF234,F012vsF34andF0123vsF4)withnosignificantdifferencesinthefivegroups(P>0.05forall).CONCLUSION:One

简介：Hepaticencephalopathy(HE)isasevereneuropsychiatricsyndromethatmostcommonlyoccursindecompensatedlivercirrhosisandincorporatesaspectrumofmanifestationsthatrangesfrommildcognitiveimpairmenttocoma.AlthoughtheetiologyofHEisnotcompletelyunderstood,itisbelievedthatmultipleunderlyingmechanismsareinvolvedinthepathogenesisofHE,andoneofthemainfactorsisthoughttobeammonia;however,theammoniahypothesisinthepathogenesisofHEisincomplete.Recently,ithasbeenincreasinglydemonstratedthatinflammation,includingsystemicinflammation,neuroinflammationandendotoxemia,actsinconcertwithammoniainthepathogenesisofHEincirrhoticpatients.Meanwhile,agoodnumberofstudieshavefoundthatcurrenttherapiesforHE,suchaslactulose,rifaximin,probioticsandthemolecularadsorbentrecirculatingsystem,couldinhibitdifferenttypesofinflammation,therebyimprovingtheneuropsychiatricmanifestationsandpreventingtheprogressionofHEincirrhoticpatients.TheantiinflammatoryeffectsofthesecurrenttherapiesprovideanoveltherapeuticapproachforcirrhoticpatientswithHE.ThepurposeofthisreviewistodescribetheinflammatorymechanismsbehindtheetiologyofHEincirrhosisanddiscussthecurrenttherapiesthattargettheinflammatorypathogenesisofHE.

简介：Overthepastfewdecades,non-alcoholicfattyliverdisease(NAFLD)hasbecomeone,ifnotthemostcommon,causeofchronicliverdiseaseaffectingbothadultsandchildren.Theincreasingnumberofcasesatanearlyageisthemostworryingaspectofthispathology,sinceitprovidesmoretimeforitsevolution.Thespectrumofthisdiseaserangesfromliversteatosistosteatohepatitis,fibrosisandinsomecases,hepatocellularcarcinoma.NAFLDmaynotalwaysbeconsideredabenigndiseaseandhepatologistsmustbecautiousinthepresenceoffattyliver.Thisshouldprompttheuseoftheavailableexperimentalmodelstounderstandbetterthepathogenesisandtodeveloparationaltreatmentofadiseasethatisdangerouslyincreasing.Inspiteofthegrowingefforts,thepathogenesisofNAFLDisstillpoorlyunderstood.InthepresentarticlewereviewthemostrelevanthypothesesandevidencethataccountfortheprogressionofNAFLDtonon-alcoholicsteatohepatitis(NASH)andfibrosis.TheavailableinvitroandinvivoexperimentalmodelsofNASHarediscussedandrevisedintermsoftheirvalidityintranslationalstudies.Thesestudiesmustbeaimedatthediscoveryofthestillunknowntriggersormediatorsthatinducetheprogressionofhepaticinflammation,apoptosisandfibrosis.