Efeitos Terapêuticos da Tripla Antiagregação Plaquetária em Pacientes Femininas Idosas com Diabetes e Infarto Agudo do Miocárdio

BackgroundDual antiplatelet therapy (DAPT) is the cornerstone treatment of acute myocardial infarction (AMI).ObjectiveThe present study aimed to investigate the efficacy and safety of triple antiplatelet therapy (TAPT) in elderly female patients with diabetes and ST segment elevation myocardial infarction (STEMI), who had undergone percutaneous coronary intervention (PCI).MethodsWe designed a randomized, single-blind study. Control group A (97 elderly male patients with diabetes and STEMI, whose CRUSADE scores were < 30) received aspirin, ticagrelor, and tirofiban. A total of 162 elderly female patients with diabetes and STEMI were randomly divided into two groups according to CRUSADE score. Group B (69 patients with CRUSADE score > 31) received aspirin and ticagrelor. Group C (93 patients with CRUSADE score < 30) received aspirin, ticagrelor and tirofiban. P values < 0.05 were considered statistically significant.ResultsCompared to the findings in group A, post-PCI Thrombolysis in Myocardial Infarction (TIMI) grade 3 blood flow and TIMI myocardial perfusion grade 3 were significantly less prevalent in group B (p < 0.05). When compared to groups A and C, the incidence of major adverse complications was significantly higher in group B (p < 0.05).ConclusionTAPT could effectively reduce the incidence of major complications in elderly female patients with diabetes and STEMI. However, close attention should be paid to hemorrhage in patients receiving TAPT. (Arq Bras Cardiol. 2020; [online].ahead print, PP.0-0)     

利用CNV-seq技术产前诊断Pallister-Killian综合征胎儿一例

应用拷贝数变异测序(copy number variation sequencing,CNV-seq)技术鉴别来源不明的胎儿标记染色体,明确其遗传物质的来源,并探讨此技术在产前诊断中的应用价值。讨论Pallister-Killian综合征(Pallister-Killian syndrome,PKS)的临床特征及遗传学特点,提高对此类罕见染色体疾病的认识。该病例因在妊娠中期超声发现胎儿异常而行羊水穿刺进行CNV-Seq检测,同时分析胎儿和父母的核型。羊水CNV-Seq结果示该样本12号染色体p13.33-p11.1处检测到拷贝数为3.5、片段大小为34.70 Mb的嵌合重复区域;羊水染色体核型结果为47,XY,+i(12)(p10)[58]/46,XX[42],综合上述结果考虑为PKS。通过结合超声结果,综合应用染色体G显带核型分析和CNV-seq技术能准确确认染色体异常片段来源,在产前有效诊断PKS患者。     

Exosomes from miRNA‐126‐modified endothelial progenitor cells alleviate brain injury and promote functional recovery after stroke

AimsWe previously showed that the protective effects of endothelial progenitor cells (EPCs)‐released exosomes (EPC‐EXs) on endothelium in diabetes. However, whether EPC‐EXs are protective in diabetic ischemic stroke is unknown. Here, we investigated the effects of EPC‐EXs on diabetic stroke mice and tested whether miR‐126 enriched EPC‐EXs (EPC‐EXs^miR126) have enhanced efficacy.MethodsThe db/db mice subjected to ischemic stroke were intravenously administrated with EPC‐EXs 2 hours after ischemic stroke. The infarct volume, cerebral microvascular density (MVD), cerebral blood flow (CBF), neurological function, angiogenesis and neurogenesis, and levels of cleaved caspase‐3, miR‐126, and VEGFR2 were measured on day 2 and 14.ResultsWe found that (a) injected EPC‐EXs merged with brain endothelial cells, neurons, astrocytes, and microglia in the peri‐infarct area; (b) EPC‐EXs^miR126 were more effective than EPC‐EXs in decreasing infarct size and increasing CBF and MVD, and in promoting angiogenesis and neurogenesis as well as neurological functional recovery; (c) These effects were accompanied with downregulated cleaved caspase‐3 on day 2 and vascular endothelial growth factor receptor 2 (VEGFR2) upregulation till day 14.ConclusionOur results indicate that enrichment of miR126 enhanced the therapeutic efficacy of EPC‐EXs on diabetic ischemic stroke by attenuating acute injury and promoting neurological function recovery.     

TGFβ promotes YAP‐dependent AXL induction in mesenchymal‐type lung cancer cells

The acquisition of chemoresistance remains a major cause of cancer mortality due to the limited accessibility of targeted or immune therapies. However, given that severe alterations of molecular features during epithelial‐to‐mesenchymal transition (EMT) lead to acquired chemoresistance, emerging studies have focused on identifying targetable drivers associated with acquired chemoresistance. Particularly, AXL, a key receptor tyrosine kinase that confers resistance against targets and chemotherapeutics, is highly expressed in mesenchymal cancer cells. However, the underlying mechanism of AXL induction in mesenchymal cancer cells is poorly understood. Our study revealed that the YAP signature, which was highly enriched in mesenchymal‐type lung cancer, was closely correlated to AXL expression in 181 lung cancer cell lines. Moreover, using isogenic lung cancer cell pairs, we also found that doxorubicin treatment induced YAP nuclear translocation in mesenchymal‐type lung cancer cells to induce AXL expression. Additionally, the concurrent activation of TGFβ signaling coordinated YAP‐dependent AXL expression through SMAD4. These data suggest that crosstalk between YAP and the TGFβ/SMAD axis upon treatment with chemotherapeutics might be a promising target to improve chemosensitivity in mesenchymal‐type lung cancer.

Abbreviations

AUC

area under the curve

AXL

AXL receptor tyrosine kinase

BCL2

B‐cell lymphoma 2

CTD2

cancer target discovery and development

CTGF

connective tissue growth factor

DEG

differentially expressed genes

DOXO

doxorubicin

EMT

epithelial–mesenchymal transition

Eto

etoposide

FDA

Food and Drug Administration

ITGB3

integrin beta‐3

MAPK

mitogen‐activated protein kinase

MMP2

matrix metalloproteinase‐2

MMP9

matrix metalloproteinase‐9

mRNA

messenger RNA

NF‐κB

nuclear factor kappa‐light‐chain‐enhancer of activated B cells

SBE

SMAD binding element

SERPINE1

serpin family E member 1

siRNA

small interfering RNA

ssGSEA

single‐sample gene set enrichment analysis

TCGA

The Cancer Genome Atlas

TGFβ

transforming growth factor beta

YAP

Yes‐associated protein

YAP8SA

mutants of inhibitory phosphorylation site at eight serine to Alanine of YAP

ZEB1

zinc finger E‐box binding homeobox 1

ZEB2

zinc finger E‐box‐binding homeobox 2

     

母亲龋易感性与婴儿口腔微生物多样性关系的纵向探究

目的通过检查有龋及无龋母亲的口腔卫生状况,并通过随访收集其婴儿1个月(1月龄)及6个月(6月龄)的唾液样本测序分析,观察母亲患龋情况对其婴儿口腔微生物多样性的影响。方法通过筛查收集1月龄婴儿的唾液样本;于首次采样时记录母亲的口腔卫生状况,根据母亲患龋情况将婴儿分为母亲有龋组(简称有龋组)和母亲无龋组(简称无龋组),跟踪随访至婴儿6个月时再次收集唾液样本。通过高通量测序的方法,分析婴儿不同月龄微生物多样性的变化。结果本研究随访受试者10例(男6例,女4例),其中有龋组7例,无龋组3例,各组间的微生物群落多样性Shannon指数均无显著性差异(P>0.05)。无龋组婴儿1月龄至6月龄时微生物群落的物种组成有较大变化;有龋组婴儿在1月龄和6月龄时组内各样本间物种组成均差异较大;1月龄时两组微生物群落较相似,而至6月龄时两组婴儿唾液的物种组成已开始发生变化。结论有龋组婴儿口腔内菌群多样性总体高于无龋组,在1月龄至6月龄间婴儿口腔内微生物物种的多样性及丰度均有了不同程度的提高。     

出凝血异常普通外科病人围手术期静脉血栓栓塞症防治策略

易栓症是外科围手术期静脉血栓栓塞症(VTE)的防治重点。对于接受手术的止凝血障碍病人,需要谨慎评估VTE的个体风险,同时兼顾手术和麻醉的性质、出血障碍类型和严重程度、年龄、体重指数(BMI)、血栓形成史、恶性肿瘤和其他高危共患病。VTE风险应与已知出血障碍病人使用抗凝相关的出血风险平衡。实验室检查有助于发现和判断血栓与出血的病因,对病人的止凝血代偿能力作出评估,并对抗凝药物的合理使用提供依据。对上述病人,建议术后不常规使用药物预防血栓,尤其是血友病病人,但围手术期因子替代和止血药物的过度应用仍存在导致血栓的风险。使用低分子肝素(LMWH)和直接口服抗凝剂前应评估肾小球滤过率。当血小板计数<50×109/L,LMWH短期减量应用可能相对安全,监测抗Хa水平可用于调整中重度血小板减少症病人LMWH的剂量。主要消化道出血停止和重新使用华法林应至少相隔7 d。对于高血栓栓塞风险和术后高出血风险病人,术后当晚和术后第1天减量应用直接口服抗凝剂是一种可取的做法。     

不同强度经皮穴位电刺激对胸腔镜手术患者术后免疫功能的影响

目的观察不同强度经皮穴位电刺激(TEAS)对胸腔镜手术患者术后免疫功能的影响。方法将68例行胸腔镜手术治疗的患者按住院先后顺序采取随机数字表法分为低强度TEAS组、中强度TEAS组、高强度TEAS组和电针组,每组17例。4组术后在镇痛泵治疗的基础上,给予不同强度的TEAS或电针治疗。观察4组患者治疗前后T淋巴细胞亚群、自然杀伤细胞(NK细胞)和血清免疫球蛋白水平。结果4组术后CD3﹢和CD4﹢T淋巴细胞、NK细胞、血清IgM、血清IgG的水平均较术前降低(P<0.05);术后48 h低强度TEAS组和高强度TEAS组的CD3﹢和CD4﹢T淋巴细胞、NK细胞、血清IgM的水平均低于电针组(P<0.05);中强度TEAS组和电针组比较差异无统计学意义(P>0.05)。4组术后CD8﹢T淋巴细胞、CD4﹢/CD8﹢以及血清IgG水平组间比较,差异无统计学意义(P>0.05)。结论中强度TEAS能够有效改善胸腔镜手术后患者的免疫功能。