简介：Recentstudieshaverevealedthatthepropertyofdrugismainlyassociatedwiththebody'ssubstanceandenergyme-tabolism.ThepresentstudyaimedtoevaluatethedrugpropertyofPoria,calledFuling(FL)intraditionalChinesemedicine(TCM),intermsofitseffectsonthesubstanceandenergymetabolisminratmodelsofcold-deficiencyandheat-deficiencysyndromes,comparedwithAconitiLateralisRadixPraeparaia,calledFuzi(FZ)inTCM,withhotproperty,andAnemarrhenaeRhizoma,calledZhimu(ZM)inTCM,withcoldproperty,asreferencedrugs,respectively.Theappearancescore,toeandrectaltemperaturesoftheanimalstreatedwereassessedatdifferenttimepoints.Severalindicesinvivocorrelatedwithsubstanceandenergymetabolism(glucokinas,phosphoglyceratekinase,cytochromecreductase,cytochromecoxydase,andNa^+-K^+-ATPase),endocrinesystem(triiodothyronine,thyroxine,and17-hydroxycorticosteroid),nervoussystem(acetylcholinesterase),andcyclicnucleotidesystemweredetermined.Thechangesinappearancescoreandindicesinvivosuggestedthesuccessfulestablishmentofcold-deficiencyandheat-deficiencysyndromemodels.FZreversedthedecreasedlevelsofindices(substanceandenergymetabolismandendocrinesystem)andalleviatedthesyndromeofcold-deficiencymodel,andZMshowedobviouslytherapeuticeffectonheat-deficiencysyndrome(appearancescore,substanceandenergymetabolism,andendocrinesystem).FLcouldalleviatecold-deficiencysyndromeandraisethedecreasedlevelsofglucokinas,phosphoglyceratekinase,cytochromecreductaseandtriiodothyronineincold-deficiencymodel,buthadnosignificanteffectonheat-deficiencysyndrome.DrugpropertyofFLwasinferredastrendingto"flatandwarm",whichstillneedfurtherstudy.Itwasadvisabletoadoptbothcold-deficiencyandheat-deficiencymodelstostudythedrugswith"flat"property.

简介：TodeterminetheregulatoryeffectsofestrogenandcytokineIL-6andIL-8onthegrowthofepithelialovariancancer(OVCA),wefirstexaminedthestatusofestrogenreceptors(ERαandERβ),IL-6receptor(IL-6Rαandgp130),andIL-8receptor(IL-8RAandIL-8RB)onfiveepithelialOVCAcelllinesbysemiquantitativeRT-PCRandWesternblotanalysis.Resultsshowedthattheexpressionsofthesereceptorswerevariableonthefivecells.ThoseOVCAcellsexpressingthereceptorswereselectedtostudyrelatedmolecularmechanism.MTTassaywasperformedtoobservetheeffectsof17β-estradiol(E2),IL-6andIL-8oncellproliferation.WediscoveredthatE2markedlypromotedtheproliferationofCAOV-3andOVCAR-3cellinatime-anddose-dependentmanner.Tamoxifen(Txf),anERinhibitor,completelyblockedtheproliferationoftheE2-inducedcells,andIL-6-or/andIL-8-neutralizingantibodyonlyshowedpartiallyblockingactivity.IL-6andIL-8wereabletosignificantlystimulateCAOV-3andOVCAR-3cellproliferationinatime-anddose-dependentmanner,whichhadapotentialsynergisticeffectonCAOV-3cellsbutnotonOVCAR-3cells.Thecellproliferationinducedbythesetwocytokineswasabolishedcompletelybytheirspecificneutralizingantibodies,partiallybyTxf,butnotbyunrelatedgoatIgG.Takentogether,ourresultssuggestedthatestrogen,IL-6andIL-8couldmodulateOVCAgrowthbyformingareciprocalcascadewithamplifyingeffect.Cellular&MolecularImmunology.

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简介：AbstractObjective:To analyze the proportion of peripheral regulatory T cells (Tregs) and the expression of the immune checkpoint molecules T-cell immunoglobulin and ITIM domain (TIGIT) and CD226 on Tregs in patients with recurrent spontaneous abortion (RSA).Methods:The proportion of CD3+CD4+CD25+Foxp3+ Tregs and the expression levels of CD226 and TIGIT on Tregs in 30 normal pregnant women and 28 patients with RSA were determined via flow cytometry.Results:The proportion of Tregs in the RSA group (4.41 % ± 1.54%) was significantly lower than that in the control group (5.27% ± 1.52%, P = 0.0374). Compared with the normal pregnant women, patients with RSA showed decreased TIGIT expression (54.75 ± 9.70% vs. 63.07 ± 12.48%, P = 0.0066) and increased CD226 expression on Tregs (25.59% ± 8.22% vs. 20.46% ± 6.97%, P = 0.0168). The ratio of CD226 to TIGIT in the RSA group (0.48 ± 0.19) was higher than that in the control group (0.34 ± 0.15, P = 0.0027). The proportion of TIGIT+CD226+ Tregs was significantly lower in patients with RSA (9.30% ± 4.95% vs. 13.43% ± 4.72%, P = 0.0020) than in the controls.Conclusions:Patients with RSA show a reduced proportion of Tregs and an imbalance in the expression of TIGIT and CD226 on Tregs.

简介：自然地发生的产生胸腺的CD4+CD25+规章的T(Treg)房间被认为在自我忍耐起一个中央作用。支持Treg房间的开发的精确信号留下逃犯，却可观证据建议T房间在胸腺在遇到抗原的costimulatory分子，cytokines，TCR的性质和壁龛或上下文起重要作用。从Treg房间的TCR的分析证明了这张人口的一个大比例从CD4+CD25-房间与TCR比较有更高的热望到自我抗原，那外部抗原为他们的发展，维护，或扩大被要求。Treg房间被显示了在圆周经历扩大，多半由自我抗原的存在调整了。许多研究证明了在忍耐正式就职的Treg房间的参与是抗原特定的，与甚至错配MHC在移植/接枝对主人疾病(GVHD)，autoimmunity，癌症，和怀孕。论文研究在身体正直的维护为自我反应的Treg房间结束了一个重要角色。基于那些研究，我们假设自我反应的Treg细胞在所有健康个人之中被分享并且认出一样的自我抗原和他们的TCR，这为定义健康自我的每个器官的很少主导的抗原编码。这些主导的自我抗原能被认为是“通用有免疫力的代码”。

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简介：在维持平衡外部有免疫力的system.Recent的一个重要角色学习的CD4+CD25+规章的T(TR)房间玩证明了TR房间可以也在压制反肿瘤免疫者反应起一个关键作用。以便调查TR极化上的肿瘤免疫者微型环境和它的影响，糟糕产生免疫性的肿瘤房间线D5(C57BL/6，H-2b)，产生免疫性的肿瘤房间线FBL3(C57BL/6，H-2b)并且H22BALB/c，H-2d)被用来建立syngeneic/allogeneic，糟糕产生免疫性/产生免疫性的混合淋巴细胞肿瘤房间文化(MLTC)。我们的结果表明在告知的splenocytes与D5肿瘤房间刺激了的syngeneic的MLTC的CD4+CD25+T房间的比例与H22房间比那高(0.43%对0.044%，并且类似的结果在与.Thesplenocytes从更高表明的房间比从D5肿瘤的allogeneicMLTC，房间，和splenocytes刺激了机智的CD4+CD25+房间分配的D5肿瘤的syngeneicMLTC与上层清液刺激了的D5肿瘤房间(0.39%对0.04%)刺激的allogeneicsplenocytes出现了TGF-1和Th2面向的cytokines(IL-4和IL-10)在糟糕产生免疫性的肿瘤房间的syngeneicMLTC的上层清液被统治。我们的结果为学习位于肿瘤免疫者监视下面的机制以及为肿瘤免疫疗法提供了有用信息。

简介：AbstractBackground:Pancreatic adenocarcinoma (PAAD) is an extremely lethal malignancy. Identification of the functional genes and genetic variants related to PAAD prognosis is important and challenging. Previously identified prognostic genes from several expression profile analyses were inconsistent. The regulatory genetic variants that affect PAAD prognosis were largely unknown.Methods:Firstly, a meta-analysis was performed with seven published datasets to systematically explore the candidate prognostic genes for PAAD. Next, to identify the regulatory variants for those candidate genes, expression quantitative trait loci analysis was implemented with PAAD data resources from The Cancer Genome Atlas. Then, a two-stage association study in a total of 893 PAAD patients was conducted to interrogate the regulatory variants and find the prognostic locus. Finally, a series of biochemical experiments and phenotype assays were carried out to demonstrate the biological function of variation and genes in PAAD progression process.Results:A total of 128 genes were identified associated with the PAAD prognosis in the meta-analysis. Fourteen regulatory loci in 12 of the 128 genes were discovered, among which, only rs4887783, the functional variant in the promoter of Ring Finger and WD Repeat Domain 3 (RFWD3), presented significant association with PAAD prognosis in both stages of the population study. Dual-luciferase reporter and electrophoretic mobility shift assays demonstrated that rs4887783-G allele, which predicts the worse prognosis, enhanced the binding of transcript factor REST, thus elevating RFWD3 expression. Further phenotypic assays revealed that excess expression of RFWD3 promoted tumor cell migration without affecting their proliferation rate. RFWD3 was highly expressed in PAAD and might orchestrate the genes in the DNA repair process.Conclusions:RFWD3 and its regulatory variant are novel genetic factors for PAAD prognosis.

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简介：摘要：目的 对某地区药店质量管理经营现状进行研究，优化药品监管模式。方法 结合药店质量管理经营实际状况,在对药店许可验收和日常检查监管环节存在的问题进行分析基础上,提出药品监管模式优化策略。结论 从引入新型监管模式、加强法律法规及日常质量管理培训和提高企业人员积极性以及效率有效性等方面对做好药店质量管理提出对策建议。 

简介：摘要：目的 对某地区药店质量管理经营现状进行研究，优化药品监管模式。方法 结合药店质量管理经营实际状况,在对药店许可验收和日常检查监管环节存在的问题进行分析基础上,提出药品监管模式优化策略。结论 从引入新型监管模式、加强法律法规及日常质量管理培训和提高企业人员积极性以及效率有效性等方面对做好药店质量管理提出对策建议。 

简介：Toinvestigatetheroleofnegative-regulatoryfactorsA20,IRF-4andTRAF4ofthetoll-likereceptor(TLR)signalpathwaysinimmunologicalpathogenesisofKawasakidisease(KD),48childrenwithKawasakidisease,16childrenwithinfectiousdisease(ID)and16age-matchedhealthychildrenwerestudied.Reverse-transcriptionPCR(RT-PCR)andreal-timePCRwereusedtoevaluatetheexpres-sionlevelsofnegative-regulatoryandeffectivefactorsintoll-likereceptor4(TLR4)signalpathwaysandproinflammatoryfactorsinperipheralbloodmonocyte/macrophage(MC).Inthisstudy,expressionlevelsofTLR4,MD-2,MyD88,IRAK-4,TRAF6,TAK1,andTAB2mRNAinKDgroupweredetectedtobeelevatedsignificantlyduringacutephaseofKD.Transcriptionlevelsofnegative-regulatoryfactorsA20,IRF-4andTRAF4mRNAinKDorIDpatientsincreasedremarkably.However,expressionsofIRF-4andTRAF4inKDpatientsweredetectedtobelowerthanthatinIDpatients,exceptthattran-scriptionlevelsofA20werefoundtobehigherthanthatinIDpatients.Simultaneously,expressionsofproinflammatorycytokinessuchasL-1β,IL-6andTNF-αinKDpatientsweresignificantlyelevatedcom-paredwiththoseinIDpatients.Furthermore,itwasfoundthatstimulationoflipopolysaccharide(LPS)remarkablyup-regulatedtheexpressionsofnegative-regulatoryfactorsA20,IRF-4andTRAF4inKDpa-tientsorhealthyvolunteers.ThemRNAlevelsofallthethreefactorsinKDpatientswerefoundtobelowerthanthatinthelatter.Inaddition,transcriptionlevelsofIRF-4andTRAF4inKDpatientswithcoronaryarterylesion(KD-CAL~+)weredetectedtobelowerthanthoseinKDpatientswithoutcoronaryarterylesion(KD-CAL~-)duringacutephase,whilethatofA20inKD-CAL~+groupwerelowerthanthatinthelatter.AndthelevelsofexpressionsofproinflammatorycytokinesinKD-CAL~+groupwerefoundtobehigherthanthoseinKD-CAL-group(P<0.01).Thesefindingssuggestthataberrantexpressionofnegative-regulatoryfactorsofTLRssignalpathwaysmaybeinvolved

简介：Xenogeneic胸腺移植能高效地在athymic接受者导致特定的有免疫力的忍耐到施主抗原。然而，许多裸体老鼠在xenogeneic胸腺移植以后患自体免疫的疾病(帮助)超过10个星期。CD4+CD25+Foxp3+规章的T(Treg)房间最近决心在在人和老鼠使忍耐有免疫力起一个枢轴的作用。因此，我们在受不了的老鼠帮助的猪胸腺接枝裸体的圆周调查了Treg房间的这subpopulation。我们的结果证明鼠标CD4+CD25+T房间和到CD4+T房间的CD4+CD25+Foxp3+Treg房间的比率上的Foxp3，CTLA-4和GITR的表达式显著地在受不了的鼠标帮助的猪胸腺接枝裸体的圆周被减少，与健康的猪或鼠标胸腺接枝裸体人鼠标相比。而且，在受不了的老鼠帮助的猪胸腺接枝裸体的老鼠CD4+CD25+T房间在xenogeneic与对应物相比在抑制免疫力的功能显示出更多的严重缺乏猪或syngeneic胸腺接枝裸体人老鼠没有帮助。因此，减少的频率，改变的显型和在猪胸腺接枝裸体人鼠标的鼠标CD4+CD25+Treg房间的功能的缺乏可以在这个模特儿贡献帮助的开发。

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