简介:Inthepresentstudy,aseriesofnovelnitricoxide-hydrogensulfidereleasingderivativesof(S)-3-n-butylphthalide((S)-NBP)weredesigned,synthesized,andevaluatedaspotentialantiplateletagents.CompoundNOSH-NBP-5displayedthestrongestactivityininhibitingthearachidonicacid(AA)-andadenosinediphosphate(ADP)-inducedplateletaggregationinvitro,with3.8-and7.0-foldmoreeffectivenessthan(S)-NBP,respectively.Furthermore,NOSH-NBP-5couldreleasemoderatelevelsofNOandH2S,whichwouldbebeneficialinimprovingcardiovascularandcerebralcirculation.Moreover,NOSH-NBP-5couldrelease(S)-NBPwhenincubatedwithratbrainhomogenate.Inconclusion,thesefindingsmayprovidenewinsightsintothedevelopmentofnovelantiplateletagentsforthetreatmentofthrombosis-relatedischemicstroke.
简介:摘要目的RNA结合基序蛋白10(RBM10)突变体(N392S)的鉴定及探究其对肺腺癌细胞功能的影响。方法收集天津医科大学肿瘤医院生物样本库108例肺腺癌(LUAD)组织样本,进行RBM10外显子的sanger测序。将野生型RBM10及RBM10突变体(N392S)通过慢病毒感染的方法分别转入肺癌细胞,转入空载体的细胞作为对照。采用细胞增殖实验(MTT)、平板克隆实验、划痕实验和侵袭实验分析RBM10突变体对肺癌细胞增殖和迁移能力的影响,通过实时荧光定量聚合酶链反应(qPCR)检测含有和不含第9外显子的NUMB转录本核糖核酸(RNA)水平的变化分析RBM10突变体对NUMB第9外显子的剪切调控作用。组间数据比较采用t检验。结果在LUAD组织样本中检测到一种新的RBM10错义突变(N392S);与空载体对照细胞比较,表达野生型RBM10的A549-RBM10-Wild和H358-RBM10-Wild细胞增殖明显变慢(1.28±0.01比1.43±0.03,t=7.866,P<0.01;1.27±0.03比1.70±0.05,t=11.840,P<0.01),而表达突变体RBM10(N392S)的A549-RBM10-Mut和H358-RBM10-Mut细胞增殖能力高于表达野生型RBM10细胞系(1.49±0.13比1.28±0.01,t=2.851,P<0.05;1.62±0.10比1.27±0.03,t=5.823,P<0.01);在平板克隆实验中,表达RBM10突变体的A549和H358细胞克隆形成率高于表达野生型RBM10的A549和H358细胞克隆形成率(53.00±3.61比28.60±4.34,t=9.675,P<0.01;42.40±3.98比18.60±4.34,t=9.047,P<0.01);细胞划痕实验显示,野生型RBM10较对照组抑制肺腺癌细胞的迁移(56.28±13.49比100.00±10.27,t=4.465,P<0.01),而突变体较野生型则失去抑制细胞迁移的能力(138.94±20.18比56.28±13.49,t=5.898,P<0.01);Transwell实验证实,野生型RBM10较对照组抑制肺腺癌细胞的迁移(158.00±36.81比497.25±38.20,t=15.093,P<0.01),突变体较野生型RBM10失去抑制肺腺癌细胞迁移的能力(474.00±48.63比158.00±36.81,t=12.424,P<0.01);分析RBM10对NUMB第9外显子的剪切调控作用,随着野生型RBM10质粒浓度的递增,野生型RBM10促进NUMB第9外显子(NUMB-EXON 9)的跳读使得NUMB短剪接转录本水平的增加,而随着RBM10(N392S)质粒浓度的递增,NUMB短剪接转录本水平没有变化。结论RBM10突变体(N392S)丧失了野生型RBM10抑制LUAD细胞增殖与迁移的功能,并可能通过调控NUMB蛋白剪切影响LUAD细胞功能。
简介:摘要目的比较S-ReSC和S.T.O.N.E.评分系统对经皮肾镜取石术后结石清除率的预测价值。方法收集2016年9月至2019年4月在本院接受F24标准通道经皮肾镜取石术治疗的113例结石患者的临床资料,根据术后结石是否清除分为结石清除组82例和结石残留组31例。根据S-ReSC和S.T.O.N.E.评分系统分别对患者进行S-ReSC和S.T.O.N.E.评分,采用受试者工作特征(ROC)曲线分析S-ReSC和S.T.O.N.E.评分系统对结石清除的预测价值,采用多因素logistic回归模型分析影响结石清除的因素。结果结石清除组手术时间、术中出血量和住院时间均低于结石残留组(t=2.325、2.726、2.301,P<0.05);结石清除组S-ReSC评分和S.T.O.N.E.总评分低于结石残留组(t=10.673、5.147,P<0.05),两组S.T.O.N.E.评分中结石最大截面积、皮肾通道距离、肾积水程度、累及肾盏个数四项评分分布比较,差异有统计学意义(χ2=9.296、4.543、4.292、8.533,P<0.05),两组结石密度评分比较,差异无统计学意义(χ2=2.105,P>0.05);S-ReSC评分、S.T.O.N.E.总评分、结石最大截面积、肾积水程度、累及肾盏个数与结石清除状态有相关性(P<0.05),而皮肾通道距离、结石密度与结石清除状态无相关性(P>0.05);S-ReSC评分、S.T.O.N.E.评分预测结石清除的ROC曲线下面积(AUC)分别为0.875(95%CI:0.796~0.953)、0.751(95%CI:0.655~0.847),S-ReSC评分预测结石清除的AUC大于S.T.O.N.E.评分(Z=2.117,P=0.034);多因素logistic回归分析显示,手术时间、S-ReSC评分和S.T.O.N.E.评分是结石清除的影响因素。结论S-ReSC和S.T.O.N.E.评分系统均是预测经皮肾镜取石术后结石清除率的有效方法,S-ReSC评分的预测准确性更好。
简介:目的探讨特勤人员S_ⅠS_ⅡS_Ⅲ综合征特点。方法选取Ⅰ、Ⅱ、Ⅲ标准导联同时存在S波的患者心电图,分析Ⅰ、Ⅱ、Ⅲ、aVR、V1、V5导联R波与S波比值、心电轴及年龄、体型以及病史等相关参数。结果(1)S_ⅠS_ⅡS_Ⅲ综合征发生率低,仅0.9%(51/5639人);(2)51例S_ⅠS_ⅡS_Ⅲ综合征患者心电轴偏移范围宽,在-110°~+178°,平均(27.49±79.74)°,其中心电轴正常19例(37.3%)、右偏15例(29.4%)、左偏13例(25.5%)、心电轴不确定4例(7.8%);(3)S_ⅠS_ⅡS_Ⅲ综合征多见于体质量指数偏低即呈瘦长体型年轻人,体质量指数〈24.0者占58.8%(30/51);(4)疗养体检无其他异常发现。结论健康特勤人员可出现S_ⅠS_ⅡS_Ⅲ综合征,多见于瘦长体型年轻人,可能系正常心电图变异,但诊断要慎重,须经心脏超声及X射线等检查排除器质性疾病。
简介:AIM:Toinvestigatetheeffectsofhydrogen-richsaline(HRS)onmicrogliaactivationandSirtuintype1(Sirt1)inratswithN-methyl-N-nitrosourea(MNU)-inducedretinitispigmentosa(RP).METHODS:Ratsweredividedintonorm(N)group,model(M)groupandHRS(H)group.RatsinMandHgroupsweregivensalineandHRSrespectivelypriortoandafteradministrationofMNU.Atoneday(d1)andd3afterwards,electroretinogramandhistologicalexaminationwereperformedtoconfirmtheeffectsofHRSonretinalfunctionandstructureofMNU-inducedRP.Immunofluorescencestainingofanti-ionizedcalcium-bindingadaptermolecule1(Iba1),amakerofmicrogliacells,wasperformed,withquantitativereal-timepolymerasechainreaction(qRT-PCR)foritsmRNAquantification.Moreover,Sirt1mRNAandproteinexpressionintheretinasweredetectedbyWesternblotandqRT-PCR.RESULTS:HRSpreservedtheretinalfunctionandmitigatedthereductionofphotoreceptordegenerationinMNU-treatedretinas.ThepresenceofmicrogliacellswassomewhatmoreobviousinHgroupthanthatinMgroupatd1.HRSsuppressedthefurtheractivationofmicrogliacells,withthenumberofmicrogliacellslessthanthatofMgroupatd3.ResultsofqRT-PCRofIba1wereconsistentwiththoseofimmunofluorescencestaining,withthemRNAexpressionofIba1inHgroupmoreintensivethanthatofMgroupatd1(P<0.05),whilelessthanthatofMgroupatd3(P<0.05).Furthermore,theSirt1mRNAandproteinexpressiondecreasedafterMNUadministration,whileHRSmitigatedtheMNU-induceddownregulationofSirt1.CONCLUSION:HRScaneffectivelykeepmicrogliaactivationinducedbyMNUtoanappropriateextent,whileupregulateSirt1inMNU-inducedRP.
简介:Thequestforneuroprotectivedrugstoslowtheprogressionofneurodegenerativediseases(NDDs),includingAlzheimer'sdisease(AD),Parkinson'sdisease(PD),andHuntington'sdisease(HD),hasbeenlargelyunrewarding.Preclinicalevidencesuggeststhatrepurposingquetiapine,lithium,valproate,fluoxetine,donepezil,andmemantineforearlyandpre-symptomaticdisease-modificationinNDDsmaybepromisingandcanspareregulatorybarriers.Theliteratureofthesepsychotropicsinearlystageandpre-symptomaticAD,PD,andHDisreviewedandpropitiousfindingsfollow.Mildcognitiveimpairment(MCI)phaseofAD:salutaryhumanrandomizedcontrolledtrialfindingsforlow-doselithiumand,inselectedpatients,donepezilawaitreplication.Pre-symptomaticAD:humanepidemiologicaldataindicatethatlithiumreducesADrisk.Animalmodelstudies(AMS)revealencouragingresultsforquetiapine,lithium,donepezil,andmemantine.EarlyPD:valproateAMSfindingsshowpromise.Pre-symptomaticPD:lithiumandvalproateAMSfindingsareencouraging.EarlyHD:uncontrolledclinicaldataindicatenon-progressionwithlithium,fluoxetine,donepezil,andmemantine.Pre-symptomaticHD:lithiumandvalproateareauspiciousinAMS.Manyotherpromisingfindingsawaitingreplication(valproateinMCI;lithium,valproate,fluoxetineinpre-symptomaticAD;lithiuminearlyPD;lithium,valproate,fluoxetineinpre-symptomaticPD;donepezilinearlyHD;lithium,fluoxetine,memantineinpre-symptomaticHD)arereviewed.Dose-andstage-dependenteffectsareconsidered.Suggestionsforsignal-enhancementinhumantrialsareprovidedforeachNDDstage.
简介:QUALITATIVESTUDYOFSIALOMUCINSCHANGESDURINGN-METHYL-N-NITROSOUREA-INDUCEDCOLONICCARCINOGENESISINMICEWangQiang王强;WangYuanhe王元和;...
简介:Neurotrophicfactorscompriseessentialsecretedproteinsthathaveseveralfunctionsinneuralandnon-neuraltissues,mediatingthedevelopment,survivalandmaintenanceofperipheralandcentralnervoussystem.Therefore,neurotrophicfactorissuehasbeenextensivelyinvestigatedintothecontextofneurodegenerativediseases.Alzheimer'sdiseaseandParkinson'sdiseaseshowchangesintheregulationofspecificneurotrophicfactorsandtheirreceptors,whichappeartobecriticalforneuronaldegeneration.Indeed,neurotrophicfactorspreventcelldeathindegenerativeprocessesandcanenhancethegrowthandfunctionofaffectedneuronsinthesedisorders.Basedonrecentreports,thisreviewdiscussesthemainfindingsrelatedtotheneurotrophicfactorsupport–mainlybrain-derivedneurotrophicfactorandglialcellline-derivedneurotrophicfactor–inthesurvival,proliferationandmaturationofaffectedneuronsinAlzheimer'sdiseaseandParkinson'sdiseaseaswellastheirputativeapplicationasnewtherapeuticapproachforthesediseasesmanagement.
简介:AbstractObjective:The prevalence of midline birth defects, such as gastroschisis, has increased worldwide, over the last few decades. This study aims to explore the prevalence, maternal epidemiological characteristics, and natural history of neonates affected by gastroschisis at the University Hospital of León city, Nicaragua.Methods:Data were collected from the birth defect surveillance system of the Hospital Oscar Danilo Rosales (HEODRA). The analysis included all pregnancies that had gastroschisis complications between January 1 and December 31, 2020. The prevalence of gastroschisis was calculated according to maternal age. The mothers were interviewed, and the clinical records of the newborns were reviewed.Results:Among the 4,460 deliveries included in this study, four cases of gastroschisis were identified, including three live births and one stillbirth. The gastroschisis rate was 8.9 per 10,000 live births (95% confidence interval [CI]: 0.18-17.8). The prevalence among mothers younger than 20 years and those older than 20 years was 26.4 (95% CI: -3.43 to 56.25) and 3.01 (95% CI: 2.89-8.90)/10,000 births, respectively. Mothers of gastroschisis-affected fetuses were of rural origin (n = 3), had normal body mass indexes (n = 3), were exposed to tobacco and wood smoke (n = 2), and one was exposed to pesticides during the periconceptional period. Primary closure of the gastroschisis was performed on one patient, and complex gastroschisis for intestinal perforation was observed in another patient. The mean hospitalization duration was 33 days, and two patients were discharged alive.Conclusions:Gastroschisis was a significant birth defect among children delivered at HEODRA in 2020. Its prevalence in Nicaragua was higher than that in other countries in the region. All complicated pregnancies were young women with unplanned pregnancies, from rural areas, with exposure to secondhand smoke, and without vitamin supplements before or during the first trimester of pregnancy. Only 67% of infants survived after hospital discharge.