目的 探究阿司匹林联合低分子肝素治疗高凝状态复发性流产(RSA)的临床效果。方法 选择2018年9月—2019年9月我院收治的80例高凝状态RSA患者,随机分为两组,各40例。比较两组胎儿的结局情况;比较两组治疗前、妊娠12周后D-二聚体、血小板聚集率;比较两组用药安全性。结果 观察组足月产率、活产率高于对照组,流产率低于对照组,差异有统计学意义(P＜0.05);治疗后,观察组D-二聚体、血小板聚集率均低于对照组,差异有统计学意义(P＜0.05);两组不良反应率之间,差异无统计学意义(P＞0.05)。结论 阿司匹林、低分子肝素联合治疗高凝状态RSA的效果显著,可以改善胎儿结局,降低D-二聚体、血小板聚集率,改善孕妇机体高凝状态,且安全性高。

目的 通过生物信息学方法,分析阿司匹林抗结直肠癌的作用机制。方法 在DrugBank 5.1.5中查找阿司匹林的直接作用蛋白靶点(direct protein targets,DPTs);构建阿司匹林DPTs的蛋白质-蛋白质相互作用(protein-protein interaction,PPI)网络并分析相关信号通路;从GEO数据库中获取结直肠癌表达谱芯片数据,筛选中心度最高的20个结直肠癌差异表达基因作为Hub基因;将DPTs相互关联基因与结直肠癌Hub基因求交集,确认阿司匹林抗结直肠癌的潜在作用靶点,分析其在TCGA数据库结肠腺癌样本中的表达情况,并进行GO功能富集分析和KEGG信号通路分析。最终通过RT-PCR和WB实验验证阿司匹林抗结直肠癌的潜在靶点。结果 在DrugBank 5.1.5中确定了11个阿司匹林DPTs,KEGG信号通路分析发现其中6个DPTs(EDNRA,IKBKB,NFKB2,NFKBIA,PTGS2,TP53)与癌症的发生发展有关。将DPTs相关联基因与筛选的20个结直肠癌Hub基因求交集,发现5个基因(CDK1,AURKA,CCNB1,MAD2L1,TPX2)可能是阿司匹林抗结直肠癌的潜在作用靶点,其在TCGA数据库结肠腺癌样本中均表达上调,基因功能主要富集于细胞周期调控。RT-PCR和WB实验结果显示阿司匹林可以降低人结肠癌细胞中CDK1,AURKA,CCNB1,MAD2L1,TPX2的mRNA水平和蛋白表达。结论 CDK1,AURKA,CCNB1,MAD2L1,TPX2可能是阿司匹林抗结直肠癌的潜在靶点,其可能通过影响细胞周期调控发挥抗肿瘤作用。

Objective To analyze the mechanism of aspirin against colorectal cancer(CRC)by bioinformatic analysis. Methods DrugBank 5.1.5 was used to identify direct protein targets (DPTs) of aspirin. The protein-protein interaction (PPI) network of DPTs was constructed and involved signaling pathways were analyzed. CRC-associated gene expression datasets were downloaded from GEO database, and the top twenty differentially expressed genes with the highest degree were screened out as Hub genes. Common genes between the genes associated with the DPTs and the Hub genes of CRC were the potential targets of aspirin against CRC. The potential targets in TCGA database colon adenocarcinoma (COAD) samples were examined. GO functional enrichment analysis and KEGG signaling pathway analysis of the potential targets were performed. The potential targets of aspirin against CRC cells were verified by reverse transcription-polymerase chain reaction (RT-PCR) and western blot (WB). Results Eleven DPTs of aspirin were identified in DrugBank 5.1.5. KEGG signaling pathway showed that 6 genes (EDNRA, IKBKB, NFKB2, NFKBIA, PTGS2, TP53) were associated with the occurrence and development of CRC. By intersecting 20 Hub genes of CRC with genes associated with the DPTs of aspirin, it was found that 5 genes (CDK1, AURKA, CCNB1, MAD2L1, TPX2) might be the potential targets of aspirin against CRC. They were all up-regulated in TCGA-COAD samples, and the gene functions were mainly enriched in cell cycle regulation. The results of RT-PCR and WB showed that aspirin could down-regulate the mRNA and protein expression levels of CDK1, AURKA, CCNB1, MAD2L1 and TPX2 in human colon cancer cells respectively. Conclusion CDK1, AURKA, CCNB1, MAD2L1 and TPX2 could be potential targets of aspirin against CRC by affecting the progress of cell cycle regulation.

目的 探讨长期吸烟史对高危脑卒中患者口服阿司匹林二级预防效果的影响。方法 将2012年8月—2014年8月医院口服阿司匹林二级预防的高危脑卒中患者115例作为研究对象,根据有无吸烟史分为无吸烟史组(34例)和吸烟史组(81例),其中36例吸烟时间≥20 a(长期吸烟史组)、45例吸烟时间1～19 a(短期吸烟史组)。随访12个月,测定血小板颗粒膜蛋白(GMP-140)、D-二聚体(D-D)、纤维蛋白原(FIB)、组织型纤溶酶原激活物(t-PA)、血小板膜糖蛋白CD61、CD62p,记录1年阿司匹林抵抗和临床终点事件发生率。结果 长期吸烟史组治疗前后GMP-140、D-D、FIB、CD61、CD62p高于短期吸烟史组和无吸烟史组,t-PA低于短期吸烟史组和无吸烟史组,且短期吸烟史组和无吸烟史组组间比较,差异有统计学意义(P＜0.05);长期吸烟组阿司匹林抵抗发生率和临床终点事件发生率分别为33.33%、30.56%,高于无吸烟史组的8.82%、8.82%,差异有统计学意义(P＜0.05),其余组组间比较差异无统计学意义(P＞0.05)。结论 长期吸烟史会使脑卒中患者存在血栓前状态,增加阿司匹林抵抗和临床终点事件的发生几率。

Objective To explore effects of long-term smoking on secondary prevention for oral aspirin in high-risk stroke patients. Methods A total of 115 high-risk stroke patients who orally took aspirin for secondary prevention in our hospital from August 2012 to August 2014 were selected as the study subjects. According to smoking or not, they were divided into non smoking history group (34 cases) and smoking history group (81 cases). Among them, 36 cases whose smoking time was ≥ 20 years were included in the long-term smoking history group, and 45 cases whose smoking time was 1 to 19 years were included in the short-term smoking history group. The patients were followed up for 12 months. The platelet granule membrane protein (GMP-140), D-dimer (D-D), fibrinogen (FIB), tissue plasminogen activator (t-PA), platelet membrane glycoprotein CD61 and CD62p were determined. The incidence rates of 1-year aspirin resistance and clinical outcome events in the three groups were recorded. Results Before and after treatment, GMP-140, D-D, FIB, CD61 and CD62p in long-term smoking history group were higher than those in short-term smoking history group and non smoking history group while T-PA was lower, and there were significant differences between short-term smoking history group and non smoking history group (P<0.05). The incidence rates of aspirin resistance and clinical outcome events in long-term smoking history group (33.33%, 30.56%) were higher than those in non smoking history group (8.82%, 8.82%)(P<0.05), but there was no significant difference among other groups (P>0.05). Conclusion Long-term smoking history will cause prethrombotic state in stroke patients and increase the incidence rates of aspirin resistance and clinical outcome events.

目的 研讨阿司匹林广泛用于高危血栓、栓塞抗凝的预防治疗应用。方法 查阅参考文献,结合临床实践,新口服抗凝药疗效终点卒中和体循环栓塞方面为基准。结果 界於CHADS2和CHA2DS2-VASc 评分所涵盖的风险和差异因素,后期华法林与新口服抗凝药可能取舍或并存。结论 在危险分层,卒中抗拴防凝治疗中,我国房颤患者不建议继续服用阿司匹林。

Objective To Study and discuss the applications for prevention and treatment of high risky thrombosis and embolism anticoagulation of Aspirin. Methods Combining literature consultation and clinical practice,making stroke and general circulation embolism of oral anticoagulant curative effect terminal point as the base. Results According to the risky and different factors covered by CHADS2 and CHA2DS2-VASc in the later stage, warfarin and the new oral anticoagulant can be taken together or abandon one of them. Conclusion In the risky factors classification and stroke anticoagulant therapy, we suggest that the atrial fibrillation patients should not take Aspirin.