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  • 简介:AIMToinvestigatetheroleofthecomplement5a(C5a)/C5areceptor(C5aR)pathwayinthepathogenesisofacuteliverfailure(ALF)inamousemodel.METHODSBALB/cmicewererandomlyassignedtodifferentgroups,andintraperitonealinjectionsoflipopolysaccharide(LPS)/D-galactosamine(D-GalN)(600mg/kgand10μg/kg)wereusedtoinduceALF.TheKaplanMeiermethodwasusedforsurvivalanalysis.Serumalanineaminotransferase(ALT)levels,atdifferenttimepointswithina1-wkperiod,weredetectedwithabiochemistryanalyzer.Pathologicalexaminationoflivertissuewasperformed36hafterALFinduction.Serumcomplement5(C5),C5a,tumornecrosisfactor-α(TNF-α),interleukin(IL)-1β,IL-6,high-mobilitygroupproteinB1(HMGB1)andsphingosine-1-phosphatelevelsweredetectedbyenzyme-linkedimmunosorbantassay.Hepaticmorphologicalchangesat36hafterALFinductionwereassessedbyhematoxylinandeosinstaining.ExpressionofC5aR,sphingosinekinase1(SphK1),p38-MAPKandp-p38-MAPKinlivertissue,peripheralbloodmononuclearcells(PBMCs)andperitonealexudativemacrophages(PEMs)ofmiceorRAW264.7cellswasanalyzedbywesternblotting.C5aRmRNAlevelsweredetectedbyquantitativereal-timePCR.RESULTSActivationofC5andup-regulationofC5aRwereobservedinlivertissueandPBMCsofmicewithALF.BlockadeofC5aRwithaC5aRantagonist(C5aRaC5aRa)significantlyreducedthelevelsofserumALT,inflammatorycytokines(TNF-α,IL-1βandIL-6)andHMGB1,aswellasthelivertissuedamage,butincreasedthesurvivalrates(P<0.01forall).BlockadeofC5aRdecreasedSphK1expressioninbothlivertissueandPBMCssignificantlyat0.5hafterALFinduction.C5aRapretreatmentsignificantlydownregulatedthephosphorylationofp38-MAPKinlivertissuesofALFmiceandC5astimulatedPEMsorRAW264.7cells.Moreover,inhibitionofp38-MAPKactivitywithSB203580reducedSphK1proteinproductionsignificantlyinPEMsafterC5astimulation.CONCLUSIONTheC5a/C5aRpath

  • 标签: 尖锐的肝失败 C5a/C5aR P38-MAPK 鞘氨醇 kinase 1
  • 简介:【摘要】

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  • 简介:AbstractBackground:Drug-coated balloons (DCBs) have emerged as potential alternatives to drug-eluting stents in specific lesion subsets for de novo coronary lesions. Quantitative flow ratio (QFR) is a method based on the three-dimensional quantitative coronary angiography and contrast flow velocity during coronary angiography (CAG), obviating the need for an invasive fractional flow reserve procedural. This study aimed to assess the serial angiographic changes of de novo lesions post-DCB therapy and further explore the cut-off values of lesion and vessel QFR, which predict vessel restenosis (diameter stenosis [DS] ≥50%) at mid-term follow-up.Methods:The data of patients who underwent DCB therapy between January 2014 and December 2019 from the multicenter hospital were retrospectively collected for QFR analysis. From their QFR performances, which were analyzed by CAG images at follow-up, we divided them into two groups: group A, showing target vessel DS ≥50%, and group B, showing target vessel DS <50%. The median follow-up time was 287 days in group A and 227 days in group B. We compared the clinical characteristics, parameters during DCB therapy, and QFR performances, which were analyzed by CAG images between the two groups, in need to explore the cut-off value of lesion/vessel QFR which can predict vessel restenosis. Student’s t test was used for the comparison of normally distributed continuous data, Mann-Whitney U test for the comparison of non-normally distributed continuous data, and receiver operating characteristic (ROC) curves for the evaluation of QFR performance which can predict vessel restenosis (DS ≥50%) at mid-term follow-up using the area under the curve (AUC).Results:A total of 112 patients with 112 target vessels were enrolled in this study. Group A had 41 patients, while group B had 71. Vessel QFR and lesion QFR were lower in group A than in group B post-DCB therapy, and the cut-off values of lesion QFR and vessel QFR in the ROC analysis to predict target vessel DS ≥50% post-DCB therapy were 0.905 (AUC, 0.741 [95% confidence interval, CI: 0.645, 0.837]; sensitivity, 0.817; specificity, 0.561; P < 0.001) and 0.890 (AUC, 0.796 [95% CI: 0.709, 0.882]; sensitivity, 0.746; specificity, 0.780; P < 0.001).Conclusions:The cut-off values of lesion QFR and vessel QFR can assist in predicting the angiographic changes post-DCB therapy. When lesion/vessel QFR values are <0.905/0.890 post-DCB therapy, a higher risk of vessel restenosis is potentially predicted at follow-up.

  • 标签: Quantitative flow ratio Drug-coated balloons De novo coronary lesions Cut-off value Receiver operating characteristic curves
  • 简介:Reporter:TheDecisionoftheThirdPlenarySessionoftheEighteenthCPCCentralCommitteeproposedtostartupapolicythatallowscoupleswithonespousebeinganonly-childtohavetwochildren(hereinafterreferredtoas'thepolicyoftwochildrenforoneonly-childspouse').Thepolicyhasreceivedwideattentionfromthesociety.Whydoesthegovernmentchoosetostartupthepolicyatthisstage?

  • 标签: 独生子女 计划生育 配偶 孩子 副部长 委员会
  • 简介:摘要:对于尾水衬管没有预留尾水检修平台搭设孔的老电站,尾水检修平台采用悬空搭设方式,解决了机组大修若开挖搭设孔后没有足够时间养护混凝土的难题,使得搭设过程安全高效且方便,大大降低劳动强度。

  • 标签: 尾水检修平台 悬空搭设 设计
  • 简介:抗原特定的CD8T房间的显型和功能仔细与治疗学的种痘的功效被联系。这里,我们证明有在Freund的助手的LCMVgp33-41肽(KAV)的多重免疫能与CD127和CD62L分子的低表示导致KAV特定的CD8T房间。禁止的受体PD-1也在怒气和淋巴节点在KAV特定的CD8T房间上在KAV特定的CD8T房间,和它的表示水平的实质的部分上被表示高得多什么时候与那些相比在外部血。而且,KAV特定的CD8T房间能明确地在vivo杀死搏动KAV的目标房间,但是效率是低的。这些数据建议有在Freund的助手的肽的那张主要增加的种痘时间表能与部分功能的疲劳得到像受动器的显型的抗原特定的CD8T房间,它可以仅仅对病原体提供短期的保护。

  • 标签: LCMV T细胞 肽疫苗 表型