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简介：AbstractIt has been reported that liver fibrosis could be reversed after eliminating liver injuries. This article systematically summarizes the evidence of fibrosis regression based on histology, liver stiffness, and serum biomarkers, and discusses several clinically relevant challenges. Evidence from liver biopsy has been regarded as the gold standard in the assessment of fibrosis regression. Semi-quantitative staging and grading systems are traditionally and routinely used to define regression. Recently, the predominantly regressive, indeterminate, and predominantly progressive score was proposed, based on the regressive features from "hepatic repair complex" , to provide additional information regarding the quality of fibrosis. For non-invasive assessment, although liver stiffness and serum biomarkers could be applied to reflect the dynamic changes of liver fibrosis, other confounding factors such as liver inflammation have to be considered. In conclusion, both histology and non-invasive methods can provide evidence regarding fibrosis regression. The predictive value of fibrosis regression in long-term prognosis warrants further investigation.

简介：BackgroundMyocardialfibrosisisoneprocessofthevariousheartdiseases,whichleadstocommonpathologicalchangeswhenitdevelopstoacertainstage.Itisthemaincauseofventricularremodelingwhicheventuallyleadstodifferentdegreesofcardiacdysfunction,malignantarrhythmiasandsuddencardiacdeath.Manystudieshaveshownthatvariouscytokinesplayaveryimportantroleinthedevelopmentofmyocardialfibrosis.Thispaperreviewsthelatestresearchesontheroleofcytokinesinmyocardialfibrosis.

简介：BackgroundMyocardialfibrosisplaysacriticalroleintheprocessofdiabeticcardiacremolding.MicroRNAs(miRNAs)areendogenous,smallnon-codingRNAsthatnegativelyregulategeneexpressionindiversebiologicalandpathologicalprocesses.However,therolesofmiRNAsinmyocardialfibrosishavenotbeenwellelucidated.Inthepresentstudy,miRNAsprofilesinthefibroticmyocardiumofdb/dbmiceandmiRNAsexpressioninTGF-β1-stimulatedmousecardiacmyofibroblastswasexamined.MethodsHeartfunctionof18-week-olddb/dbmiceanddb/mcontrolmicewasdetectedbyechocardiography.miRNAexpressionprofileindiabeticmyocardiumwasdetectedbymiRNAmicroarray.Quantitativereal-timePCRwasusedtodeterminetheexpressionoffibrosis-relatedgenesandmiRNAprecursorsofinterest.Westernblotwasusedtodetectthelevelsoffibrosis-relatedproteins,activatedSmad3andtotalSmad3.ResultsTheresultofechocardiographyshowedthatleftventricularsystolicanddiastolicfunctionwasimpairedin18-week-olddb/dbmicewithoutsignificantchangeofejectionfraction(EF)andfractionalshortening(FS).Fibrosis-relatedgenesexpressionwasupregulatedandtheamountofphosphorylatedSmad3wasincreasedsignificantlyinthediabeticmyocardium.miRNAsdysregulationwasshownindiabeticmyocardium,sixty-eightmiRNAs,includingmiR-208b,miR-29b,miR-26bandmiR-30e,wereincreasedovertwo-fold,meanwhile,sixty-twomiRNAsweredecreasedmorethantwo-foldinthemyocardiumofdb/dbmicecomparedtodb/mcontrols.InparallelwithasignificantupregulationofCol1a1,Col3a1andCTGFmiRNAexpression,miR-208b,miR-29b,miR-26bandmiR-30eprecursorswerealsoshowntobeupregulatedinTGF-β1-inducedC57bl/6mousecardiacmyofibroblasts.ConclusionsmicroRNAsweredysregulatedindiabeticmyocardium,withtheactivationofTGF-β/smad3pathway,contributingtodiabeticmyocardialfibrosis.

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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.

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简介：肝纤维变性和它的结束阶段后果，肝硬化，代表最后的普通小径几乎所有长期的肝疾病。对肝的星形的房间激活的研究，细胞外的矩阵合成和降级和cytokines和chemokines的贡献的不平衡进一步阐明了机制内在的纤维变性。而且，在适应的主人和天生的免疫系统的变化的澄清加速了我们在肝发炎和纤维变性之间的协会的理解。肝的纤维变性的机制的继续的说明提供了纤维变性前进和回归的一个全面模型。这评论总结在纤维变性的领域里被做了的改进的当前的概念。

简介：AbstractImportance:Vitamin A (or retinol) has considerable antioxidative and anti-inflammatory attributes and it may have protective effects on the respiratory health of patients with cystic fibrosis (CF). This issue, however, remains controversial.Objective:The purpose of the present study was to investigate the relationship between serum retinol levels (SRL) and force expiratory volume in 1 second (FEV1) in patients with CF.Methods:All patients with pancreatic insufficiency attending the CF Department of "Agia Sofia" Children’s Hospital in Athens, Greece, aged 6 to 19 years during the 2012-2016 period, who could perform spirometry effectively, were included in the study. The impact of SRL on FEV1 was examined longitudinally and analyzed with generalized estimating equations.Results:The study included 231 patients and 851 SRL measurements were performed. In 25 (3.2%) cases the SRL were below the 5th percentile of reference distribution; none was above the 95th percentile. The analysis showed that SRL was positively correlated with the FEV1 (P < 0.001).Interpretation:In this sample of children and adolescents with CF, vitamin A deficiency was rare. Our results suggest a positive relationship between SRL and FEV1.

简介：INTRODUCTIONAmajorfunctionoftheintestinalepitheliumistocontroltheamountoffluidenteringintoandbeingabsorbedfromthelumen.Inhealthyconditions,netfluidmovementfollowsanabsorptivevector,althoughsignificantsecretionalsotakesplacetosubservedigestivefunction.Thus,the

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简介：以前的学习显示出那个aerosolized信号变换器和antisenseoligodeoxynucleotide(ASON)禁止了的transcription-1(STAT1)的使活跃之物在牙槽的巨噬细胞(Ams)的STATI和ICAM-1mRNA和蛋白质的表达式并且减少TGF-的集中，在在bleomycin(BLM)的bronchioalveolarlavage液体(BALF)的PDGF和TNF-导致了老鼠肺的纤维变性。STAT1ASON的管理改善了在老鼠的齿槽炎肺的纤维变性。然而，进一步的调查被需要决定是否从纤维变性上的STAT1ASON的管理有效果。这研究在导致BLM的老鼠在煽动性的调停人，hydroxyproline和类型和类型骨胶原mRNA的表情上调查了aerosolizedSTAT1ASON的效果肺的纤维变性。结果证明aerosolization使用的STAT1ASON能改善齿槽炎和纤维变性，禁止煽动性的调停人，的表情减少hydroxyproline的内容，并且在导致BLM的老鼠在肺织物压制类型和类型骨胶原mRNA的表情肺的纤维变性。这些结果建议aerosolizedSTAT1ASON可能在肺的纤维变性的处理被看作有希望的新策略。

简介：Aims：TotaltriterpenoidfromPrunellavulgarisL.（TTP）,knownasmedicinehad,hadapreventiveeffectagainsthepaticsteatosisinourpreviouswastoevaluatewhetherTTPcouldimproveliverfibrosisnismofactionofTTPonhepaticstellategrowthfactor（PDGF）.atraditionalChinesestudy.Ourobjectiveinratsandtoinvestigatethemecha-cell（HSC）proliferationinducedbyplatelet-derivedgrowthfactor（PDGF）.

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简介：AIM:Toevaluatethecorrelationofshearwaveelastography(SWE)resultswithliverfibrosishistologyandquantitativefunctionreserve.METHODS:Weeklysubcutaneousinjectionof60%carbontetrachloride(1.5mL/kg)wasgivento12caninesfor24wktoinduceexperimentalliverfibrosis,witholiveoilgivento2controlcanines.At24wk,liverconditionwasevaluatedusingclinicalbiochemistryassays,SWEimaging,lidocainemetabolitemonoethylglycine-xylidide(MEGX)test,andhistologicfibrosisgrading.Clinicalbiochemistryassayswereperformedattheinstitutionalcentrallaboratoryforroutineliverfunctionevaluation.Liverstiffnesswasmeasuredintriplicatefromthreedifferentintercostalspacesandexpressedasmeanliverstiffnessmodulus(LSM).PlasmaconcentrationsoflidocaineanditsmetaboliteMEGXweredeterminedusinghigh-performanceliquidchromatographyrepeatedinduplicate.Liverbiopsysampleswerefixedin10%formaldehyde,andliverfibrosiswasgradedusingthemodifiedhistologicalactivityindexKnodellscore(F0-F4).Correlationsamonghistologicgrading,LSM,andMEGXmeasureswereanalyzedwiththePearsonlinearcorrelationcoefficient.RESULTS:At24wkliverfibrosishistologicgradingwasasfollows:F0,n=2(control);F1,n=0;F2,n=3;F3,n=7;andF4,n=2.SWELSMwaspositivelycorrelatedwithhistologicgrading(r=0.835,P<0.001).Specifically,theF4grouphadasignificantlyhigherelasticmodulusthantheF3,F2,andF0groups(P=0.002,P=0.003,andP=0.006,respectively),andtheF3groupalsohadasignificantlyhighermodulusthanthecontrolF0group(P=0.039).LSMwasnegativelyassociatedwithplasmaMEGXconcentrationsat30min(r=-0.642;P=0.013)and60min(r=-0.651;P=0.012),timeto?ofthemaximumconcentration(r=-0.538;P=0.047),andtheareaunderthecurve(r=-0.636;P=0.014).Multiplecomparisonsshowedidenticaldifferencesinthesethreemeasures:significantlylowerwithF4(P=0.037)andF3(P=0.032)ascomparedtoF0a

简介：Carvedilol,nonselectiveβ-adrenoreceptorantagonist,wasshowedprotectiveeffectsagainstacutemyocardialinfarction(AMI)-inducedmyocardialinjury,however,themechanismsunderlyingtheantifibrosiseffectofcarvedilolhasnotbeenwellknown.Theaimofthepresentstudywastoinvestigatethepotentialmechanismfortheanti-fibrosiseffectofcarvedilolagainstAMI-inducedmyocardialfibrosisinrats.MethodsMaleSDratswererandomizedintotheshamgroup,LADsurgery-AMImodelgroup,AMIpluslowdoseofcarvediloltreatmentgroup(1mg/kgperday,CAR-L),AMIplusmediumdoseofcarvediloltreatmentgroup(5mg/kgperday,CAR-M)andAMIplushighdoseofcarvediloltreatmentgroup(10mg/kgperday,CAR-H).Thepassage3neonatalSDratcardiacfibroblastswereusedforhypoxia/normoxia(2h/4h)treatmentinthepresenceofcarvedilol(0,1,2and4μM).ResultsCardiacremodelingandimpairedheartfunctionwereobservedafter14-weekLADsurgerytreatment,however,andthecardiacremodelinganddecreasedejectionfraction(EF%)andfractionalshortening(FS%)wereefficientlyrescuedintheCAR-MandCAR-Hgroups.Theup-regulatedexpressionsofCol1a1,Col3a1andα-SMAatmRNAandproteinlevelsweresignificantlyreducedintheCAR-MandCAR-Hgroups.TheinvitrostudyshowedthatCol1a1,Col3a1andαSMAexpressionsatbothmRNAandproteinlevelsweredown-regulatedbycarvedilolinratcardiacfibroblastsinadose-dependentmanner.Smad3inhibitors,SIS-3andnaringenin,couldefficientlydecreaseCol1a1,Col3a1andα-SMAexpressionsinratcardiacfibroblasts.Smad3wasshownsignificantlyinactivatedincarvedilol-treatedratcardiacfibroblasts.ConclusionCarvedilolnegativelyregulatesSmad3signalpathwayandinhibitsextracellularmatrixrelatedCol1a1,Col3a1andα-SMAexpressions,contributingtotheanti-fibrosiseffectofcarvedilolagainstAMI-inducedmyocardialfibrosisinrats.

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简介：Despitetheacceptanceofphysicalactivity(PA)beingintegraltoayoungperson'shealth,childrenwithdisabilityoftenexhibitlowlevelsofPA.Inyoungpeoplewithcysticfibrosis(CF)theimportanceofexerciseanddailyPAisacknowledgedbycliniciansandtheirsupportteams,however,thereisalackofknowledgerelatedtoitsprescription.CFisarecessivegeneticdisorderaffectingthelung,pancreasandsweatglands.CFisthemostcommonlifeshorteninggeneticdiseaseintheCaucasianpopulationforwhichthereisnocure.IntheUK,CFaffectsover9000people,with4000under16yearsofage.OnlyabouthalfoftheCFpopulationcanexpecttolivebeyond40yearsofage.Besidesdrugtherapies,rehabilitativeexerciseprogrammesformanimportantcomponentoftreatmentandlongtermexerciseprogrammesareconsideredpositivetreatmentstrategies,butalllackanydetailedprescriptiveinformation.SeveralreviewsandeditorialshavehighlightedthelackofevidencebasedresearchinPAandexercisetraininginyoungpeoplewithCF;butadvocateagreaterneedforunderstandingtheroleofexerciseintherapeuticinterventions.ThepurposeofthisreviewistoupdatethereaderonthecurrentrecommendationsandevidenceinPAandexercisetrainingforyoungpeoplewithCF.ThesedevelopmentshaveextendedourunderstandingofPAandexercisetraininginchildrenandadolescentswithCF,anditsimplementationinthemanagementofthischronicdisease.