目的 探究提前停服替格瑞洛(PTD)在急性冠状动脉综合征(ACS)患者中的发生率、原因及影响因素.方法 回顾性纳入2018年1月至10月于海军军医大学(第二军医大学)长海医院心血管内科使用阿司匹林和替格瑞洛双联抗血小板治疗的ACS住院患者400例,收集患者基线资料并随访,分析ACS患者PTD的发生率、原因和影响因素.结果 出院12个月时PTD患者49例(12.2％),未PTD患者351例(87.8％).PTD组年龄>75岁、有心力衰竭病史、既往行经皮冠状动脉介入(PCI)的患者比例和血钾、尿素水平均高于未PTD组(P=0.004、0.031、0.028、0.037、0.001),使用β受体阻滞剂的患者比例和血管病变严重程度均低于未PTD组(P=0.041、0.018).呼吸困难(22.4％,11/49)、当地无药(18.4％,9/49)和出血(12.2％,6/49)是导致PTD最常见的3个原因,改良英国医学研究理事会呼吸困难指数(mMRC)评分为2级及2级以上的呼吸困难患者均停服替格瑞洛(mMRC评分1级2例,2级6例,3级2例,4级1例).Kaplan-Meier曲线分析PTD累积发生率结果显示,67.3％(33/49)的患者PTD发生在出院后90 d内.多因素logistic回归分析结果显示,年龄>75岁(OR=2.58,95％CI 1.26～5.26,P=0.009)和尿素水平升高(OR=1.17,95％CI 1.04～1.30,P=0.007)均为ACS患者PTD的独立预测因素,血管病变严重(OR=0.95,95％CI 0.92～0.98,P=0.001)是ACS患者坚持服用替格瑞洛的相关因素.结论 ACS患者双联抗血小板治疗期间PTD的发生率为12.2％.对于呼吸困难且mMRC评分为2级及2级以上的患者,临床应及时更换P2Y12受体拮抗剂.年龄>75岁为ACS患者PTD的独立预测因素,临床实践中应该高度重视服用替格瑞洛的高龄患者,关注其有无发生呼吸困难及PTD.

微粒是细胞激活或凋亡时细胞膜通过出芽形式脱落的直径约为0.1～1 μm的小囊泡,载有蛋白质、细胞因子、mRNA、微RNA等物质,发挥多种生物学效应.在动脉粥样硬化的发生和发展中,微粒在内皮细胞损伤、炎症反应、平滑肌细胞增殖和迁移等过程中发挥重要作用.循环中高水平的微粒不仅是动脉粥样硬化患者血管损伤的生物标志物,也是动脉粥样硬化的潜在诊断指标和治疗靶点.本文立足于微粒在动脉粥样硬化发生和发展中的作用,从细胞水平对相关研究进展作一综述.

Autophagy is a highly regulated intracellular process to maintain cellular homeostasis by degrading damaged proteins and organelles. Dysregulation of autophagic activity in cardiomyocytes is implicated in various heart diseases. However, the underlying mechanisms of cardiomyocyte autophagy are not yet known. In this study, the enhanced cardiomyocyte autophagy was induced by angiotensin II (0.1 μmol/L), demonstrated by the increase of double-membraned autophagosomes, BECN1 expression, and the conversion of LC3-I to LC3-II. Microarray assay showed that a total of 197 genes were differentially expressed in angiotensin II–treated cardiomyocytes, including 22 upregulated and 175 downregulated. Gene ontology functional enrichment analysis showed that nearly 50% of differentially expressed genes were related to metabolism and energy maintenance in biological process. Pathway analysis showed that most frequently represented pathways were involved in metabolism and the citric acid cycle and respiratory electron transport. Based on KEGG database, 10 differentially expressed genes were found to be involved in autophagic signaling pathways. The hub genes with high degree were predicted to regulate cardiomyocyte autophagy activity by PPI network analysis. NEDD4, the top focus hub gene, showed a clear time-dependent increased expression pattern in cardiomyocytes during angiotensin II treatment. Moreover, inhibition of NEDD4 could significantly reduce cardiomyocyte autophagy induced by angiotensin II. In summary, the cardiomyocyte autophagy–related genes were screened by microarray assay combining with bioinformatics analysis. The role of NEDD4 on cardiomyocyte autophagy might provide valuable clues to finding therapeutic targets for heart diseases.

目的 探讨急性心肌梗死(AMI)与冠脉支架后再狭窄患者抗血小板药物治疗对凝血功能的影响.方法 选取海军军医大学附属长海医院心血管内科2014年4—11月收治的93例AMI或冠脉介入治疗(PCI)术后支架内再狭窄的患者为研究对象.测定氯吡格雷的血小板抑制率(IPA)及凝血指标.根据IPA将其分为A组(IPA<50％,n=64)与B组(IPA≥50％,n=29).比较两组凝血指标并分析IPA与各凝血指标的相关性.结果 B组患者的国际标准化比值(INR)、活化部分凝血酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间(TT)均显著低于A组(P<0.05).B组患者的IPA与INR、APTT、PT、TT呈负相关(P<0.05);而A组IPA与INR、APTT、PT、TT无明显相关性(P>0.05).结论 当抗血小板药物的IPA较低时,不会对凝血功能产生影响;抗血小板药物的IPA较强时,可以增强凝血功能,从而使血栓发生率升高.

替格瑞洛是一种新型口服抗血小板药物,通过直接作用于二磷酸腺苷(ADP)受体P2Y12抑制ADP介导的血小板聚集,发挥抗血小板功能.除抑制血小板聚集外,替格瑞洛还表现出生物多效性,如增加冠状动脉血流、限制心肌梗死面积和诱发呼吸困难等.研究认为替格瑞洛的生物多效性与腺苷密切相关,但目前有关替格瑞洛对血浆腺苷浓度影响的研究结果并不一致,可能与血浆腺苷浓度的不同测定方法(尤其是终止液配比)、不同测定时间点等有关.规范血浆腺苷浓度的测定方法以及动态监测服用替格瑞洛后血浆腺苷浓度的变化,有助于进一步明确替格瑞洛对血浆腺苷浓度的影响.

替格瑞洛是一种与P2Y12受体直接、可逆结合的抗血小板药物.相比于目前临床常用的氯吡格雷,替格瑞洛起效更快、抗血小板作用更强,且个体差异较小.但是,替格瑞洛相关呼吸困难在临床也较常见,成为患者过早停药或换药的主要原因之一.目前研究认为,引发呼吸困难的原因可能与血浆腺苷水平升高有关,但受限于血浆腺苷水平较复杂的测定方法,近年的临床研究结论并不一致.该文对近年来替格瑞洛相关呼吸困难的临床研究进行了综述,内容包括呼吸困难发生率和因呼吸闲难停药率,替格瑞洛对血浆腺苷水平的影响,以及出现呼吸困难患者的临床预后和常规处置等.

Objective To investigate the in-hospital and long-term survival of acute myocardial infarction(AMI)patients treated by optimal drug therapy,primary PCI or elective PCI.Methods A retrospective study was performed on total of 3 238 AMI patients who were admitted from December 2006 to February 2016.The general condition,past medical history,family history,clinical examination and diagnosis,complications,treatment,hospital survival and cause of death,and follow-up of all patients were collected and analyzed for the long-term survival and causes of death.Results The mortality of AMI patients was 5.8%,and the mortality of the patients in the non-operation group was higher than that in the operation group(26.6% versus 2.5%);the mortality of patients in the primary PCI group was higher than that in the elective PCI group(3.5% versus 2.0%);non cardiogenic death was the leading cause of death in hospital(31.7%),followed by cardiogenic shock(30.2%).Killips classification,age,white blood cell level,ventricular fibrillation,cardiogenic shock were independent risk factors for hospital death in drug treatment groups;Killips grading,age,admission blood glucose,admission troponin,ventricular fibrillation,unused ACEI/ARB were independent risk factors for hospital death in primary PCI groups;PCI/CABG history,admission of creatinine,ventricular fibrillation,Gensini score,cardiogenic shock were independent risk factors for hospital death in elective PCI groups.The 2 046 cases of patients were followed-up,drug therapy group has a significantly higher mortality than that in the primary PCI and elective PCI groups(34.3% versus 4.6% and 5.3%);there was no statistically significant difference of follow-up mortality between the primary and elective PCI groups(P>0.05).Conclusion For patients with AMI,early PCI can improve their hospital and long-term survival.Attention should be paid to complications such as cardiogenic shock and malignant arrhythmia.More education should be conducted to certain patients characterized by elders,female or combined with diabetes,which may contribute to early detection and timely treatment of AMI,thus reduce mortality of AMI.

Journal of Cardiac SurgeryVolume 32, Issue 12 p. 809-811 IMAGES IN CARDIAC SURGERY Left atrial myxoma induced acute ST-segment elevation myocardial infarction Yunyan Zhang, Yunyan Zhang Department of Cardiology, Changhai Hospital, The Second Military Medical University, Shanghai, ChinaSearch for more papers by this authorYang Lu, Yang Lu Department of Cardiology, Changhai Hospital, The Second Military Medical University, Shanghai, ChinaSearch for more papers by this authorRuming Xu, Ruming Xu Department of Cardiology, Changhai Hospital, The Second Military Medical University, Shanghai, ChinaSearch for more papers by this authorYuchen Xiao, Yuchen Xiao Department of Cardiology, Changhai Hospital, The Second Military Medical University, Shanghai, ChinaSearch for more papers by this authorYing Gu, Corresponding Author Ying Gu gyjiangxb@126.com Department of Cardiology, Changhai Hospital, The Second Military Medical University, Shanghai, China Correspondence Y. Gu, Department of Cardiology, Changhai Hospital, The Second Military Medical University, 168 Changhai Road, Shanghai 200433, China. Email address: gyjiangxb@126.comSearch for more papers by this author Yunyan Zhang, Yunyan Zhang Department of Cardiology, Changhai Hospital, The Second Military Medical University, Shanghai, ChinaSearch for more papers by this authorYang Lu, Yang Lu Department of Cardiology, Changhai Hospital, The Second Military Medical University, Shanghai, ChinaSearch for more papers by this authorRuming Xu, Ruming Xu Department of Cardiology, Changhai Hospital, The Second Military Medical University, Shanghai, ChinaSearch for more papers by this authorYuchen Xiao, Yuchen Xiao Department of Cardiology, Changhai Hospital, The Second Military Medical University, Shanghai, ChinaSearch for more papers by this authorYing Gu, Corresponding Author Ying Gu gyjiangxb@126.com Department of Cardiology, Changhai Hospital, The Second Military Medical University, Shanghai, China Correspondence Y. Gu, Department of Cardiology, Changhai Hospital, The Second Military Medical University, 168 Changhai Road, Shanghai 200433, China. Email address: gyjiangxb@126.comSearch for more papers by this author First published: 12 December 2017 https://doi.org/10.1111/jocs.13504Citations: 3Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume32, Issue12December 2017Pages 809-811 RelatedInformation

Objective To investigate the effectiveness and safety of low dose ticagrelor in population of China.Methods Twenty healthy subjects were randomly selected,of which ten were treated with standard dose of ticagrelor and ten received low-dose ticagrelor.Blood was collected at 0 hour,0.5 hour,1 hour,2 hours,4 hours and 8 hours,respectively.Blood was collected the next day(24 hours)before taking the dose.After the third day(48 hours)and the fourth day(72 hours),blood was taken before taking the medicine.The platelet function of whole blood was detected by VerifyNow-P2Y12 system and the main adverse reactions were observed.Results There was no significant difference of platelet aggregation rate and PRU between the two groups and the standard dose ticagrelor at 0.5 hour,1 hour,2 hours,4 hours,8 hours,24 hours,48 hours and 72 hours after administration(P>0.05).After 0.5 hour,the average platelet aggregation rate was 58.5% and 53.9% in the standard and low dose groups,respectively.The platelet aggregation rate reached the peak at 2 to 4 hours after the administration,and the PAI was 98.7% and 97.1%,which were maintained at a high level at 8 hours,24 hours and 48 hours.Subjects were resistant to ticagrelor and no serious adverse events occurred.Two cases of mild bleeding occurred in the standard dose of ticagrelor group,one case occurred in the low maintenance dose of ticagrelor group,and the incidence of bleeding between the two groups had not statistically significant difference(P>0.05).Conclusion In the healthy population of China,low dose ticagrelor and standard dose of ticagrelor have a faster,stronger platelet inhibition,and does not increase the risk of bleeding.

Objective To study the in-hospital survival rate and risk factors of female acute myocardial infarction (AMI) patients.Methods A total of 2667 AMI patients were divided into male group (n=2042) and female group (n=625).The patients in female group were further divided into survival group (n=565) and death group (n=60),and their general condition,past medical history,family history,clinical examination findings,complications,therapies and in-hospital survival rate were compared and analyzed.Results The in-hospital mortality was significantly higher in female group than in male group,in patients who received PCI than in those who did not receive PCI,and in patients who received emergency PCI than in those who received elective PCI (9.6％ vs 5.3％,P＜0.01;5.1％ vs 25.7％,P＜0.01;10.1％ vs 2.5％,P＜0.01).The in-hospital outcome of female AMI patients was positively related with STEMI,erythrocyte specific volume,therapies,β-receptor blockers,use of statins and negatively related with age,severe heart failure,cardiogenic shock,atrioventricular block,AF,troponin T peak value,and postoperative creatinine level (P＜0.05,P＜0.01).Age,urea,troponin T peak value,intraartery saccular counterpulsation,use of statins were the independent risk factors for in-hospital mortality in female AMI patients (P＜0.05,P＜0.01).Conclusion More attention should be paid to the onset of disease,urea and troponin level,intraartery saccular counterpulsation and optimized drug therapies in female AMI patients.

Autophagy is a ubiquitous intracellular process for cellular homeostasis maintenance by recycling damaged protein and organelles. Dysregulation of cardiomyocytes autophagic activity is implicated in various heart diseases. Recent studies had demonstrated that long non-coding RNAs (lncRNAs) played crucial roles on modulation of autophagic activity. In this study, we first established an angiotensin II-induced autophagy model on neonatal rat cardiomyocytes. Western blot assay confirmed that the expression of Beclin 1 and the conversion of soluble LC3-I to lipid bound LC3-II were significantly increased at 12 h after angiotensin II stimulation, but the cardiomyocytes surface area and hypertrophic markers expression had no significant change. Then microarray analysis and real-time PCR were applied to detect differentially expressed lncRNAs during cardiomyocytes autophagy. A total of 1,249 lncRNAs were determined as differentially expressed, including 700 upregulated lncRNAs and 549 downregulated lncRNAs. LncRNAs subgroup analysis showed there were 43 transcribed ultra-conserved noncoding RNAs (T-UCRs) differentially expressed in cardiomyocytes autophagy, of which 26 T-UCRs were upregulated and 17 T-UCRs were downregulated. Bioinformatics analysis further showed that 94 differentially expressed lncRNAs contained potential binding sites of miR-22, a pro-hypertrophic and pro-autophagic microRNA. Therefore, these differentially expressed lncRNAs might play critical roles in cardiomyocytes autophagy. This finding would provide an experimental basis for future investigation on ischemic heart disease.

Objective To investigate the in-hospital mortality and risk factors among the very elderly acute myocardial infarction(AMI) patients.Methods A retrospective study was performed on 3 229 very elderly AMI patients who were admitted from December 2006 to February 2015.All the patients were divided into the non-elderly group(n=2 322) and the elderly group(n=907).According to their in-hospital survival condition,the patients in elderly group were assigned into the survival group(accounted for 87.1%,n=790) and death group(accounted for 12.9%,n=117).The general condition,medical history,family history,admission examination,complications,clinical diagnosis,treatment and in-hospital survival condition were compared and analyzed.Results In-hospital survival rate was positively correlated with diagnosis,treatment,red blood cell volume,postoperative hemoglobin levels,use of beta blockers and statins ratio;while it was negatively correlated with Killip 3-4 grade proportion,atrial fibrillation,cardiac shock,three degree atrioventricular block ratio,disease severity and troponin peak,all the differenceshad statistical significance(P<0.05).The in-hospital mortality risk factors for elderly patients were the ratio of STEMI,combined with cardiac shock,ventricular fibrillation,potassium levels on admission,the peak troponin and the treatment.Conclusion Active reperfusion therapy can improve the prognosis of elderly patients with AMI,while still needs to be payed attention to heart failure,cardiogenic shock and other risk factors for elderly patients and their families should strengthen education,improve the understanding of coronary heart disease and acute chest pain,early detection and early treatment,in order to improve the prognosis of elderly patients with AMI.

Objective To explore the protective effect of active component of Eclipta on hepatic injury induced by Concanavalin A(ConA) in mice.Methods Mouse hepatic injury models were established by injection of ConA(15 mg/kg) via tail vein.The effect of Eclipta extracts on serum alanine aminotransferase(ALT) and liver histology in both normal mice and hepatic injury mice was examined.A pure compound was obtained by means of bioactivity-guided isolation,and IR, ~(13)C-NMR,~1H-NMR,~1H-~(13)C HMBC and ~1'H-~(13)C HMQC were used for structural identification.Results Eclipta extracts decreased serum ALT in hepatic injury mice induced by ConA,and demonstrated anti-apoptosis effect induced by ConA in hepatocytes.Wedelolactone,a coumarin,was isolated from Eclipta,and its structure was identified on the basis of spectroscopic analysis.Wedelolactone inhibited ConA-induced T cell proliferation selectively,and completely antagonized the effect of ConA at the concentration of 10μg/mL.Conclusion Eclipta herb has hepatoprotective effect. Wedelolactone,the anti-inflammatory and anti-apoptosis active component of Eclipta,might serve as a lead compound for developing new antiinflammatory drugs.

Objective To evaluate the strengthening and restoring effects and hepatoprotective effect of Eclipta extracts.Methods Sixty Kunming mice were randomly divided into control group,low-dose Eclipta group,high-dose Eclipta group,cyclophosphamide(CY) group,low-dose Eclipta CY group and high-dose Eclipta CY group(n=10).Eclipta 8 g·kg-1·d-1 or 4 g·kg-1·d-1 were administered by oral gavage for 7 d.Immunosuppression mouse models were established by intraperitoneal injection of 0.05 g/kg CY on the fourth day of administration.The effects of Eclipta extracts on thymus index,spleen index and carbon clearance index in both normal mice and immunosuppression mice induced by CY were tested,and those on proliferation of lymphocyte and T cells induced by ConA were examined.Based on these data,strengthening and restoring effects of Eclipta were observed.Besides,70 Kunming mice were randomly divided into control group,low-dose Eclipta group,high-dose Eclipta group,CCl4 group,DDB group,low-dose Eclipta CCl4 group and high-dose Eclipta CCl4 group.20 g·kg-1·d-1 and 10 g·kg-1·d-1 Eclipta were administered by oral gavage for 7 d.Hepatic injury mouse models were established by intraperitoneal injection of 10 mL/kg CCl4 2 h after the last administration.The effects of Eclipta extracts on serum ALT,MDA,TP and T-Bil levels in both normal mice and hepatic injury mice induced by CCl4 was tested,and those on the viability of the primary culture hepatocytes were determined.Based on these data,hepatoprotective effect of Eclipta was observed. Results Eclipta extracts increased thymus index and carbon clearance index in both normal mice and immunosuppression mice induced by CY,promoted proliferation of lymphocyte and proliferation of T cells induced by ConA,reduced serum ALT and MDA levels in hepatic injury mice,and improved the viability of the primary culture hepatocytes. Conclusion Eclipta herb has strengthening and restoring effects and hepatoprotective effect.

Objective To establish a method for detection and identification of serum monocolonal components using capillary zone electrophoresis (CZE) and immunosubtraction capillary electrophoresis (IS-CZE),and to compare the results with those detected by agarose gel electrophoresis (AGE) and immunofixation electrophoresis (IFE). Methods Five hundred and thirty-two samples were screened for paraprotein separately by CZE and AGE. Sixty-four samples with paraprotein were then typed by IS-CZE and IFE. Results In comparison with AGE,the CZE system could detect 96.9% of the paraprotein. 89% of the paraprotein could be typed by IS-CZE in comparison with IFE. Self-coated antibody could meet the needs of the study. Conclusions CZE can detect and identify the paraprotein quickly and efficiently,which may be suitable to be extended to more clinical laboratories.

Objective To synthesize p - nitrophenyl -α-D-glucopyranoside as a substrate for α- glucosidase, and develope a method for testing its activity. Methods The substrate was prepared by Westphal and Feier synthesis. A quantitative method was established according to α-glucosidase' s kinetic characters on the substrate. Results A highly purified substrate (purity 99.0% ) was obtained. A kit for α-glucosidase was made with OCV 2. 5% , RCV 3. 8% , and sensitivity 85. 7% . Conclusion The kit can be reliably used in clinics.

A convenient method for quantitative analysis of the nucleosides in Fritillaria bulbs has been developed by means of thin layer chromatography and ultraviolet spectrophotometry. The MeOH extracts from four species of Fritillaria were analyzed with this method. The results show that both adenosine and thymidine in the four species are quite disparate, suggesting that the nucleosides may be responsible for the anti-coagulative activity of Fritillaria.

蟛蜞菊内酯属重要的小分子活性化合物香豆素，其活性多样，作用明确，且实现全合成，有望作为先导化合物进行新药研发。本文对其结构、提取分离方法、合成方法及药理活性进行综述。