本文選題：表沒食子兒茶素沒食子酸酯 + 膽固醇代謝��； 參考：《北京協(xié)和醫(yī)學院》2015年博士論文

【摘要】：研究背景及目的：冠狀動脈粥樣硬化性心臟病(冠心病)仍然是威脅人類健康的重要疾病。血中總膽固醇和低密度脂蛋白膽固醇(LDL-C)濃度的升高,已被確認為冠心病發(fā)生的最主要危險因素。健康的生活方式,如良好的飲食習慣可預防高脂血癥的發(fā)生。綠茶是我國傳統(tǒng)飲品,富含茶多酚,其中茶多酚單體表沒食子兒茶素沒食子酸酯(epigallocatechin gallate, EGCG)是綠茶中最具活性的分子。近年的流行病學研究提示飲用綠茶與心血管疾病死亡險呈負相關。一些基礎研究表明茶多酚可通過抑制腸道內(nèi)外源性膽固醇的吸收、增加肝臟LDL受體(LDLR)表達及活性、調(diào)節(jié)載脂蛋白的分泌等機制調(diào)節(jié)血LDL-C水平。但目前茶多酚對脂質(zhì)代謝通路基因的直接作用以及可能的分子機制仍不清楚。長鏈非編碼RNA (long nocoding RNA, IncRNA)是一類轉錄本長度超過200個核苷酸的RNA分子,能以RNA的形式在多種層面上(表觀遺傳、轉錄以及轉錄后水平)調(diào)控基因的表達,參與了劑量補償效應、基因組印記、細胞發(fā)育分化等重要生物學過程。目前越來越多的研究揭示了IncRNA在心臟發(fā)育和心血管疾病(如冠心病)中發(fā)揮了重要作用,已成為心血管領域研究的新熱點。因此,本研究通過生物芯片技術觀察茶多酚EGCG對HepG2細胞脂質(zhì)代謝通路基因和lncRNAs表達的影響,并初步探討lncRNA對脂質(zhì)代謝通路基因的調(diào)控作用。研究方法：人HepG2細胞經(jīng)茶多酚EGCG (25μM)處理24小時后,抽提RNA,質(zhì)檢合格后雜交至Human Transcriptome Array 2.0(HTA2.0)芯片,進行mRNA和IncRNAs表達譜的分析并篩選出差異表達的基因。篩選標準為倍數(shù)變化(fold change)≥1.5 且 P0.05。通過生物信息學方法對差異表達的IncRNAs進行靶基因預測,建立IncRNAs和脂代謝相關基因的可能作用關系。為進一步研究IncRNA對靶基因的調(diào)控作用,我們利用RNA干擾技術降低相關IncRNA的表達,應用實時熒光定量多聚酶鏈反應和Western blot檢測靶基因的mRNA和蛋白表達水平改變。研究結果：表達譜芯片結果顯示與對照組相比,茶多酚EGCG處理后有27條脂質(zhì)代謝相關基因表達差異具有統(tǒng)計學意義(P0.05),涉及脂質(zhì)合成、轉運與分解。其中EGCG可直接影響膽固醇平衡代謝調(diào)控的3個關鍵基因：羥甲基戊二酸單酰輔酶A還原酶(HMGCR)、LDLR及乙酰輔酶A乙酰轉移酶2(ACAT2)的表達水平。同時EGCG處理后共有285條IncRNAs表達水平有統(tǒng)計學差異(P0.05)。生物信息學靶基因預測發(fā)現(xiàn)5個脂代謝相關基因包括HMGCR和ACAT2的表達可能受IncRNA的調(diào)控,其中IncRNA NONHSAT102202對HMGCR表達可能起著順式調(diào)控作用。RNA干擾抑制IncRNA NONHSAT102202的表達后接受不同濃度EGCG (0,10,25 μM)處理,HMGCR mRNA和蛋白表達水平均顯著性增高(P0.05)。結論：茶多酚EGCG可直接影響脂質(zhì)代謝通路基因的表達,包括在膽固醇平衡調(diào)控中起關鍵作用的基因-LDLR, HMGCR和ACAT2。同時EGCG可上調(diào)或下調(diào)眾多的IncRNAo。功能研究證實IncRNA NONHSAT102202可抑制HMGCR的表達。本研究結果提示IncRNAs可能是茶多酚降膽固醇作用的一個重要分子機制。研究背景及目的：高血壓是心血管疾病的重要危險因素。在高血壓防控中,尤其應關注正常高值血壓(收縮壓120-139 mmHg,舒張壓80-89 mmHg).目前,我國約有3億人為正常高值血壓。正常高值血壓者發(fā)展為高血壓、發(fā)生心血管事件及死于心血管疾病的風險較120/80 mm Hg以下的血壓正常者明顯增高。正常高值血壓在臨床事件發(fā)生之前即可造成亞臨床的心血管靶器官損害,因此需給予積極的干預。目前有關藥物干預的循證依據(jù)不足,而采取生活方式的干預可能更具有公共健康意義。綠茶和紅茶是世界上非常受歡迎的飲品,富含茶多酚,具有抗氧化應激和抗炎癥的作用。本研究旨在系統(tǒng)評價茶多酚的攝入(綠茶或紅茶)對正常高值血壓者或高血壓患者的降壓作用。研究方法：計算機檢索MEDLINE.EMBASE.Cochrane數(shù)據(jù)庫(檢索時間均從建庫至2014年5月),語種限制為英文,全面收集有關茶多酚攝入對血壓影響的隨機對照試驗,并追查所有納入文獻的參考文獻。由兩名評價者獨立選擇研究,進行文獻的逐步篩查,并按照Cochrane系統(tǒng)評價方法,由2名評價者獨立對納入研究的質(zhì)量進行評價和資料提取。運用加權均數(shù)差(weighted mean difference, WMD)和95%置信區(qū)間(condential interval.CI)作為血壓前后變化的效應尺度。異質(zhì)性采用I2和Cochrane Q檢驗,I250%或Q檢驗0.1認為存在異質(zhì)性。若存在異質(zhì)性,采用隨機效應模型,否則運用固定效應模型進行統(tǒng)計。按照事先定義好的亞組分析探索臨床特征(干預時程、種族、茶的類型、茶多酚的劑量、健康狀況和咖啡因攝入)對茶多酚降壓效應的影響。結果：共納入25篇隨機對照試驗1,476例研究對象。其中6篇評價了茶多酚的即時降壓效應(acute effect),平均觀察時間為6.8小時；21篇評價了茶多酚的長期效應(long-term effect),中位觀察時間為12周。薈萃分析顯示茶多酚對收縮壓和舒張壓均無明顯的即時降壓效應(收縮壓,95% CI-0.62,5.46；舒張壓,95% CI-0.01,1.42)。而茶多酚的長期攝入可顯著性地降低收縮壓1.8 mmHg(95% CI-2.4.-1.1.I2=17.4%)和舒張壓1.4 mmHg(95%CI-2.2,.0.6,I2=52.5%).根據(jù)茶的類型,薈萃分析顯示綠茶可顯著性地降低收縮壓2.1 mmHg(95%CI-2.9,-1.2.I2=21.8%)和舒張壓1.7 mmHg(95%CI-2.9,-0.5,I2=59.9%),紅茶可降低收縮壓1.4 mmHg(95%CI-2.4,-0.4,I2=9.7%)和舒張壓1.1 mmHg(95%CI一1.9,-0.2.I2=22.9%).亞組分析顯示顯示攝入茶多酚≥12周后可更為顯著地降低收縮壓(WMD-2.6[95%CI-3.5,-1.7]mmHg,I2=0%)和舒張壓(WMD-2.2[95%CI-3.0,-1.3]mmHg,I2=43.3%),而攝入的茶多酚的含量、種族、是否伴隨心血管危險因素以及咖啡因的攝入對茶多酚的降壓效應無明顯作用。結論：長期的茶多酚攝入(≥12周)可顯著降低正常高值血壓者的血壓水平。背景及目的冠心病是危害人類健康的頭號殺手。我國目前有近4000萬冠心病患者,每年死于冠心病及并發(fā)癥者已超過100萬。目前對冠心病尤其是急性冠脈綜合征的患者(acute coronary syndromes, ACS)治療中,經(jīng)皮冠狀動脈支架植入術(percutaneous coronary intervention, PCI)是最為行之有效的辦法,極大地挽救了患者的生命。氯吡格雷與阿司匹林聯(lián)合應用已經(jīng)成為PCI術后的標準治療方案,能明顯減少心血管事件的發(fā)生率,降低支架內(nèi)血栓形成的風險。但是,臨床上仍然有2-3%的患者發(fā)生支架內(nèi)血栓事件。這部分患者往往存在氯吡格雷治療后的血小板高反應性(high on-treatment platelet reactivity, HTPR)。大量數(shù)據(jù)證實HTPR與PCI術后主要心血管不良事件(major adversecardiovascular events, MACE)發(fā)生有很強的相關性。其中殘余血小板的活性可能是主要關鍵因素之一。替格瑞洛是一種新型的血小板ADP受體P2Y12拮抗劑,與同樣作用于P2Y12受體的氯吡格雷不同,它無需經(jīng)過肝臟代謝,本身已是活性狀態(tài),能夠更加迅速、強效、持久的血小板抑制作用。PLATO(抑制血小板與患者轉歸)研究表明與氯吡格雷相比,替格瑞洛可顯著降低ACS患者主要復合終點事件(心血管死亡、再發(fā)心梗和卒中)的發(fā)生風險,且不增加總體出血的風險。但是,PLATO研究主要基于國外人群,此外關于替格瑞洛在HTPR患者應用的研究也不多。因此,我們通過隨機對照研究,運用快速血小板功能分析儀(VerifyNow-P2Y12)來評價替格瑞洛對PCI術后HTPR患者的抗血小板作用。并對替格瑞洛的安全性作一初步探討,從而為PCI術后HTPR患者的合理治療提供依據(jù)。研究方法連續(xù)入選2014年4月至2015年4月阜外心血管病醫(yī)院12病區(qū)住院經(jīng)冠脈造影確診為冠心病并有介入指征行PCI術的患者。所有患者術前均服用氯吡格雷常規(guī)劑量75mg至少1周或少于一周但給予300mg負荷。根據(jù)血栓彈力圖(Thrombelasography, TEG)進行初篩,當ADP抑制率50%且最大聚集幅度MA-ADP47mm,高度懷疑為HTPR,并于術后24h內(nèi)采集空腹靜脈血5m1運用VerifyNow-P2Y12系統(tǒng)檢測P2Y12反應單位(P2Y12 reaction unit, PRU), PRU≥235定義為HTPR。將HTPR患者隨機分為氯吡格雷組(150 mg qd)和替格瑞洛組(首次180 mg負荷,繼以90mg bid維持),各組分別于服藥后2、8、24 h再次采血運用VerifyNow-P2Y12分析比較兩組對血小板活性的抑制作用。所有患者進行CYP2C19*2基因型鑒定。隨訪1個月,記錄兩組MACE、出血事件及藥物不良反應情況。兩組患者均常規(guī)接受阿司匹林100mg qd。研究結果1.本研究共入選465例經(jīng)我院冠脈造影術確診為冠心病(穩(wěn)定型心絞痛或ACS)并行PCI術的患者其中有317例患者術后成功完成了TEG檢測,共有53例懷疑為HTPR。經(jīng)VerifyNow-P2Y12系統(tǒng)檢測為HTPR患者45例,依據(jù)排除標準,最后納入40例,隨機分為氯吡格雷組(n=20)和替格瑞洛組(n=20)。兩組在基線特征方面均無統(tǒng)計學差異,具有良好的可比性。2.兩組服用抗血小板藥物后,均可顯著性地降低血小板殘余活性(PRU)。與氯吡格雷組相比,替格瑞洛對血小板的抑制更為明顯(P0.001)。在各個時間點上(2,8,24 h)替格瑞洛均比氯吡格雷更有效地降低PRU水平(P0.001)。3.服用替格瑞洛后2 h,所有患者PRU位于切點值(235)以下,在8,24 h檢測PRU分別有1例(5%)及3例(15%)患者為HTPR。而氯吡格雷組,2,8,24 h檢測HTPR分別為9例(45%),8例(40%),10例(50%),兩組間HTPR發(fā)生率差異均有統(tǒng)計學差異(P0.05)。4.替格瑞洛組9例患者(45%)攜帶至少一個CYP2C19*2能缺失等位基因。在攜帶者和非攜帶者中,替格瑞洛均可顯著降低PRU水平和減少HTPR的發(fā)生率(P0.001)。提示CYP2C19*2基因變異不影響替格瑞洛的抗血小板效應。5.隨訪1個月,兩組均未發(fā)生MACE事件。替格瑞洛組有6例發(fā)生輕微出血,主要為皮膚瘀斑。1例發(fā)生小出血,為少量消化道出血。氯吡格雷組有5例輕微出血。兩組在總體出血風險方面差異無統(tǒng)計學意義。此外,替格瑞洛組有5例患者(25%)出現(xiàn)呼吸困難,與氯吡格雷組相比,差異具有統(tǒng)計學意義(P0.05)。結論1.PCR術后HTPR患者應用替格瑞洛較高劑量氯吡格雷更能快速強效地抑制血小板活性,減少HTPR發(fā)生率。2.替格瑞洛的抗血小板效應不受CYP2C19*2基因變異的影響。3.替格瑞洛沒有增加總體出血的風險,但呼吸困難發(fā)生率高于氯吡格雷組。
[Abstract]:Background and purpose: coronary atherosclerotic heart disease (coronary heart disease) remains an important disease that threatens human health. The increase in the concentration of total cholesterol and low density lipoprotein cholesterol (LDL-C) in blood has been identified as the most important risk factor for coronary heart disease. Healthy lifestyle, such as good eating habits, can be prevented. The occurrence of lipidemia. Green tea is a traditional Chinese drink rich in tea polyphenols and tea polyphenols (epigallocatechin gallate, EGCG) is the most active molecule in green tea. In recent years, epidemiological studies suggest that green tea drinking is negatively related to cardiovascular disease death risk. Some basic studies show tea. Polyphenols can inhibit the absorption of endogenous cholesterol and increase the expression and activity of LDL receptor (LDLR) in the liver, regulate the secretion of apolipoprotein and regulate the level of blood LDL-C. However, the direct effect of tea polyphenols on the lipid metabolism pathway and the possible molecular mechanism are still unclear. Long chain non coded RNA (long nocoding RNA, In) CRNA) is a class of transcriptional transcriptional RNA molecules with more than 200 nucleotides and can regulate gene expression in a variety of layers (epigenetic, transcriptional, and post transcriptional levels) in the form of RNA, and participates in important biological processes such as dose compensation, genomic imprinting, and cell development differentiation. At present, more and more studies have revealed that IncRNA is in the heart. The important role of dirty development and cardiovascular disease (such as coronary heart disease) has become a new hot spot in the research of cardiovascular field. Therefore, the effect of tea polyphenols EGCG on the gene of lipid metabolism pathway and the expression of lncRNAs in HepG2 cells is observed by biochip technology, and the effect of lncRNA on the regulation of lipid metabolism pathway is preliminarily discussed. Methods: after 24 hours' treatment of human HepG2 cells through tea polyphenols (25 u M), RNA was extracted and RNA was extracted and hybridized to Human Transcriptome Array 2 (HTA2.0) chip after quality examination. The expression profiles of mRNA and IncRNAs were analyzed and the differentially expressed genes were screened. The screening criteria were multiple (fold change) above 1.5 and through bioinformatics. The target gene was predicted for differentially expressed IncRNAs, and the possible relationship between IncRNAs and lipid metabolism related genes was established. In order to further study the regulation of IncRNA on target gene, we use RNA interference technique to reduce the expression of related IncRNA, and use real-time fluorescent quantitative polymerase chain reaction and Western blot to detect mRNA of target gene. The results of the protein expression level change. The results of the expression spectrum chip showed that compared with the control group, there were 27 differences in the expression of lipid metabolism related genes after the treatment of the tea polyphenols EGCG (P0.05), involving lipid synthesis, transport and decomposition. Among them, EGCG could directly affect the 3 key genes of the regulation of cholesterol balance metabolism: hydroxymethyl. The expression level of glutaric acid monoyl coenzyme A reductase (HMGCR), LDLR and acetyl coenzyme A acetyltransferase 2 (ACAT2). At the same time, there was a total of 285 IncRNAs expressions after EGCG treatment (P0.05). The prediction of bioinformatics target gene found that the expression of 5 lipid metabolism related genes, including HMGCR and ACAT2, may be regulated by IncRNA, including IncRN A NONHSAT102202 may play a cis role in the expression of HMGCR in the expression of.RNA interference and the expression of IncRNA NONHSAT102202 with different concentrations EGCG (0,10,25 u M) treatment, HMGCR mRNA and protein expression levels are significantly increased (P0.05). Conclusion: tea polyphenols can directly affect the expression of lipid metabolism pathway genes, including cholesterol level. Genes -LDLR, HMGCR and ACAT2., which play a key role in the regulation and control, can up or down a large number of IncRNAo. functions, which confirm that IncRNA NONHSAT102202 can inhibit the expression of HMGCR. The results of this study suggest that IncRNAs may be an important molecular mechanism of the effect of tea polyphenols on cholesterol lowering. Research background and purpose: hypertension is the heart and blood. In the prevention and control of hypertension, in the prevention and control of hypertension, we should pay special attention to normal high blood pressure (systolic pressure 120-139 mmHg, diastolic pressure 80-89 mmHg). At present, about 300 million people in our country are normal high blood pressure. Normal high blood pressure people develop hypertension, the risk of cardiovascular events and death of cardiovascular disease is less than 120/80 mm Hg Normal high blood pressure can cause subclinical cardiovascular target damage before the occurrence of clinical events. Therefore, a positive intervention is needed. The evidence of drug intervention is not evidence-based, and the intervention of lifestyle may be more public health. Green tea and black tea are very happy in the world. The purpose of this study is to systematically evaluate the antihypertensive effects of tea polyphenols (green tea or black tea) on normal high blood pressure or hypertensive patients. Research methods: the computer retrieval MEDLINE.EMBASE.Cochrane database (retrieval time from construction to May 2014) A randomized controlled trial of tea polyphenols intake on the influence of tea polyphenols intake on blood pressure was collected and all the references were reviewed. Two evaluators selected the study independently, screened the literature, and evaluated and funded the quality of the study independently by 2 evaluators according to the Cochrane system evaluation method. Material extraction. Using weighted mean difference (weighted mean difference, WMD) and 95% confidence interval (condential interval.CI) as the effect scale of the changes before and after blood pressure. Heterogeneity uses I2 and Cochrane Q test, I250% or Q test 0.1 considers the existence of heterogeneity. If heterogeneity exists, the random effect model is used, otherwise the fixed effect model is used. The effect of clinical features (intervention duration, race, tea type, tea polyphenols dose, health status and caffeine intake) on the antihypertensive effect of tea polyphenols was investigated in accordance with a pre defined subgroup analysis. Results: a total of 1476 subjects were included in 25 randomized controlled trials. 6 of them evaluated the immediate hypotension effect of tea polyphenols (acute Effect), the average observation time was 6.8 hours; 21 articles evaluated the long-term effect of tea polyphenols (long-term effect), and the median observation time was 12 weeks. The meta-analysis showed that there was no obvious immediate hypotensive effect on systolic and diastolic pressure (systolic pressure, 95% CI-0.62,5.46; diastolic pressure, 95% CI-0.01,1.42). The systolic pressure was significantly reduced by 1.8 mmHg (95% CI-2.4.-1.1.I2=17.4%) and diastolic pressure 1.4 mmHg (95%CI-2.2,.0.6, I2=52.5%). According to the type of tea, the meta-analysis showed that green tea could significantly reduce the systolic pressure 2.1 mmHg (95%CI-2.9, -1.2.I2=21.8%) and diastolic pressure 1.7 mmHg (95%CI-2.9, -0.5, and 1.4), and black tea could reduce the systolic pressure 1.4 .4, -0.4, I2=9.7%) and diastolic pressure of 1.1 mmHg (95%CI 1.9, -0.2.I2=22.9%). Subgroup analysis showed that after intake of tea polyphenols more than 12 weeks, the systolic pressure (WMD-2.6[95%CI-3.5, -1.7]mmHg, I2=0%) and diastolic pressure (WMD-2.2[95%CI-3.0, -1.3]mmHg, I2= 43.3%) were significantly reduced, and the content of tea polyphenols intake, race, and cardiovascular risk Factors and caffeine intake have no obvious effect on the antihypertensive effect of tea polyphenols. Conclusion: long-term tea polyphenols intake (more than 12 weeks) can significantly reduce the level of normal high blood pressure. Background and objective coronary heart disease is the leading killer of human health. There are nearly 40 million coronary heart disease patients in China, died of coronary heart disease and the same year. More than 1 million of the patients have been diagnosed with coronary artery disease (acute coronary syndromes, ACS). Percutaneous coronary stent implantation (percutaneous coronary intervention, PCI) is the most effective way to save the patient's life. The combination of clopidogrel and aspirin should be combined. The use of a standard treatment program after PCI can significantly reduce the incidence of cardiovascular events and reduce the risk of thrombosis in the stent. However, stent thrombosis in patients with 2-3% is still in the clinic. These patients often have high on-treatment platelet reactiv after clopidogrel treatment. Ity, HTPR). A large number of data confirmed that HTPR has a strong correlation with the major cardiovascular adverse events (major adversecardiovascular events, MACE) after PCI. The activity of residual platelets may be one of the major key factors. The vililo is a new type of platelet ADP receptor P2Y12 antagonist, which is also used in P2Y12 receptor. Unlike clopidogrel, which does not need to be metabolized by the liver and itself is active, a more rapid, powerful and persistent platelet inhibition.PLATO (inhibition of platelet and patient outcomes) studies show that, compared with clopidogrel, velogelo significantly reduces the main complex endpoint events in ACS patients (cardiovascular death, recurrent myocardial infarction and death). However, PLATO studies are mainly based on foreign populations, and there are few studies on the use of tigreloo in HTPR patients. Therefore, we used a randomized controlled study to evaluate the resistance of tigreloe to HTPR patients after PCI with a rapid platelet function analyzer (VerifyNow-P2Y12). Thrombocytopenia, and a preliminary study of the safety of T - greelo, provides a basis for the rational treatment of HTPR patients after PCI. The methods of study were continuously selected from April 2014 to April 2015 in 12 patients in Fuwai Hospital of Cardiovascular Disease, which were diagnosed as coronary heart disease with coronary artery angiography and had interventional indications for PCI. All patients were pretreated before operation. The routine dose of clopidogrel was given for at least 1 weeks or less than one week but given 300mg load. The initial screening was carried out according to the thrombus elasto map (Thrombelasography, TEG), when the ADP inhibition rate was 50% and the maximum aggregation amplitude was MA-ADP47mm, and the HTPR was highly suspected, and the 5m1 using VerifyNow-P2Y12 system in 24h in 24h was detected in 24h, and the P2Y12 reaction was detected in 24h. P2Y12 reaction unit (PRU) and PRU > 235 were defined as HTPR. to randomly divide HTPR patients into clopidogrel group (150 mg QD) and tenogelo group (first 180 mg load, followed by 90mg bid). Each group was divided into two groups to compare the inhibitory effect on platelet activity. 1 months followed up for 1 months, two groups of MACE, bleeding events and adverse drug reactions were recorded. The two groups were routinely received aspirin 100mg qd. results in 1. study, and 465 patients with coronary heart disease (stable angina or ACS) and 317 patients with coronary heart disease (stable angina or ACS) were enrolled in this study. After successful completion of the TEG test, 53 cases were suspected to be HTPR. by VerifyNow-P2Y12 system for 45 cases of HTPR patients, according to the exclusion criteria, and finally included in 40 cases, randomly divided into the clopidogrel group (n=20) and tenogelo group (n=20). The two groups were not statistically different in the baseline characteristics, with a good comparability of the.2. two groups taking antiplatelet. Compared with the clopidogrel group, the inhibitory effect of Grillo on platelets was significantly lower than that of the clopidogrel group (P0.001). At all time points (2,8,24 h), tgrel was more effective than clopidogrel in reducing PRU level (P0.001).3. after taking the 2 h of togelo, and all patients were at the cut point value (235). In 8,24 h, 1 (5%) and 3 (15%) patients were HTPR. and clopidogrel, 2,8,24 h was used to detect HTPR in 9 cases (45%), 8 (40%), 10 (50%), and there were statistically significant differences in the incidence of HTPR in group two (P0.05).4. (45%) carrying at least one CYP2C19*2 allele. In non carriers, Grillo could significantly reduce the level of PRU and reduce the incidence of HTPR (P0.001). It was suggested that the CYP2C19*2 gene mutation did not affect the platelet effect of the antiplatelet effect of 1 months, and there were no MACE events in the two groups. There were 6 cases of slight bleeding in the group of the greelo group, which was mainly caused by small bleeding in the.1 cases of skin ecchymosis, and a small amount of elimination. There were 5 cases of mild bleeding in clopidogrel group. There was no significant difference in the overall bleeding risk between the two groups.

【學位授予單位】：北京協(xié)和醫(yī)學院
【學位級別】：博士
【學位授予年份】：2015
【分類號】：R544.1

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