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High Sensitivity CRP Predicts Long-Term Mortality in Patients with Atrial Fibrillation and Evident Acute Coronary Syndrome

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International Journal of Clinical Medicine 2013年第3期4卷 137-144页

作者： christoph liebetrau Luise Gaede Sebastian Szardien Johannes Rixe Oliver Doerr Matthias Willmer Michael Weber Andreas Rolf Helge Mollmann Albrecht Elsasser Christian Hamm Holger Nef Department of Cardiology Kerckhoff Heart and Thorax CenterBad NauheimGermany Department of Cardiology and Angiology Faculty of MedicineJustus-Liebig University of GiessenGiessenGermany

Background: Atrial fibrillation (AF) is a frequent arrhythmia associated with an adverse prognostic value in patients with ACS. Risk stratification as well as diagnosis of ACS is strongly supported by biomarkers. High sensitivity CRP (hs-CRP) is known to be elevated in patients presenting with ACS as well as with ***: In total, 2034 consecutive patients with an ACS were analysed. The incidence of AF in the setting of ACS, the prognostic value of hs-CRP and the clinical outcome within 6 months were subject of the study. Death after 6 months was considered as primary endpoint. Results: The frequency of AF among patients admitted with suspected ACS was 124 (6.1%). During 6-month follow-up the mortality rate among patients with AF was significantly higher (20 [16.1%] vs 133 [6.9%];log-rank 13.72;p 0.001) compared to patients without AF. Cox regression analysis revealed an increased risk for ACS patients with AF with an adjusted HR of 2.63 (95% CI 1.48 - 3.78;p 0.001). Patients with AF showed significant higher levels of hs-CRP than patients without AF (6.01mg/dl IQR [1.7 - 17.8] vs 3.3mg/dl IQR [1.37 - 9.83];p = 0.003). By the use of multivariate Cox regression analysis, risk of mortality was higher when AF patients had higher concentrations of hs-CRP (HR 1.076;95% CI 1.02 - 1.13;p = 0.002).Conclusions: AF is a strong and independent indicator for increased mortality in patients presenting with ACS. hs-CRP predicts mortality in AF patients and should be considered for risk stratification in clinical routine.

关键词： Acute Coronary Syndrome Atrial Fibrillation Risk Stratification High-Sensitivity CRP

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Impact of triple antithrombotic therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention in real-world practice

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Journal of Geriatric Cardiology 2017年第11期14卷 679-687页

作者： Yan YAN Xiao WANG Jing-Yao FAN Shao-Ping NIE SerGio Raooseiras-Roubin Emad Abu-Assi Jose P Simao Henriques: Fabrizio D'Ascenzo Jorge Saucedo Jose R Gonzalez-Juanate Stephen B Wilton Wouter J Kikkert Ivan Nunez-Gil Albert Ariza-Sole Xian-Tao SONG Dimitrios Alexopoulos christoph liebetrau Tetsuma Kawaji Claudio Morettil Zenon Huczek Toshiharu Fujii Luis cL Correia Masa-aki Kawashiri Sasko Kedev Beijing Anzhen Hospital Capital Medical University Beijing China University Hospital Alvaro Cunqueiro Vigo Spain University Academic Medical Center Amsterdam The Netherlands Dipartimento di Scienze Mediche Divisione di Cardiologia Cittgl della Salute e della Scienza Turin Italy NorthShore University Hospital Chicago U.S.A. University Clinical Hospital of Santiago de Compostela Spain Libin Cardiovascular Institute of Alberta Calgary Canada San Carlos Hospital Madrid Spain Bellvitge Hospital Barcelona Spain University Patras Hospital Athens Greece Kerckhoff Heart and Thorax Center Frankfurt Germany Graduate School of Medicine Kyoto University Kyoto Japan University Clinical Hospital Warsaw Poland Tokai University School of Medicine Tokyo Japan Hospital Sao Rafael Salvador Brazil Kan'azawa University Graduate School of Medicine Kanazawa Japan University Clinic of Cardiology Skopje Macedonia

Objective The optimal antithrombotic regimen for patients on oral anticoagulation （OAC） after acute coronary syndrome （ACS） and percutaneous coronary intervention （PCI） remains debated. This study sought to evaluate the efficacy and safety of OAC plus clopidogrel with or without aspirin in a real-world setting. Methods We retrospectively analyzed data from an international, multi-center registry be- tween 2003 and 2014 （n = 15,401）. Patients with ACS and receiving OAC after PCI were screened. The composite primary endpoint was 1-year all-cause death, re-infarction, or severe bleeding. Results The final analysis enrolled 642 patients including 62 patients （9.7%） with OAC and clopidogrel （dual therapy）, and 580 patients （90.3%） with the combination of aspirin, OAC and clopidogrel （triple therapy）. Pa- tients on triple therapy were more often female and were more likely to have comorbidities. There was no significant difference regarding the primary end point between dual therapy with triple therapy patients [17.74% vs. 17.24%; unadjusted hazard ratio （HR）： 1.035; 95% confi- dence interval （CI）： 0.556-1.929; adjusted HR： 1.026; 95% CI： 0.544-1.937]. However, the re-infarction rate was significantly higher in dual therapy than triple therapy patients （14.52% vs. 5.34%; unadjusted HR： 2.807; 95% CI： 1.329-5.928; adjusted HR： 2.333; 95% CI： 1.078-5.047）. In addition, there was no difference between two regimes in all-cause death and severe bleeding. Conclusions In real-life patients with ACS following PCI and with an indication of OAC, triple therapy was not associated with an increased rate of adverse out- comes compared to dual therapy. Moreover, it decreased risk of re-infarction and did not increase risk of severe bleeding.

关键词： Acute coronary syndrome Oral anticoagulation Outcome Triple antithrombotic therapy

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Pathologic Q Waves and Prolonged QTc Time in Preoperative ECG Are Predictive for Perioperative Cardiovascular Events

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World Journal of Cardiovascular Diseases 2014年第10期4卷 498-509页

作者： Thomas Wolters Michael Weber Thomas Neumann Hans-Georg Strauß Andreas Luchner Manfred Seeberger Christian Mueller christoph liebetrau Svetlana Apostolovic Radmilo Jankovic Dragic Bankovic Marina Jovic Vesselin Mitrovic Holger Nef Helge Mollmann Karl Werdan Christian W. Hamm Axel Schlitt Department of Medicine III University Clinic Halle (Saale) Halle Germany Department of Medicine Clinic Grabs Grabs Switzerland Department of Cardiology Kerckhoff Heart and Thorax Center Bad Nauheim Germany Department of Medicine II Clinic Gro&szlig -Umstadt Gro&szlig -Umstadt Germany Department of Medicine II University of Regensburg Regensburg Germany Department of Cardiology University of Basel Basel Switzerland University Cardiology Clinic Ni&scaron Serbia Department of Mathematical Sciences University of Kragujevac Kragujevac Serbia Department of Medicine I University Clinic of Gie&szlig en and Marburg Gie&szlig en Germany Department of Medicine I Paracelsus-Harz-Clinic Bad Suderode Quedlinburg Germany

Aims: The value of ECG in the perioperative risk stratification under modern treatment options is uncertain. The main objective of the present analysis was to determine the usefulness of a pre-operative ECG derivation for evaluating the risk of perioperative morbidity and mortality. Methods: We performed a secondary analysis of the prospective, international, multicenter, observational “No-Risk” Study (N-terminal B-type natriuretic peptide [NT-proBNP] for the assessment of the perioperative cardiac risk after major noncardiac surgery) to determine the prognostic value of 12-lead ECG. Inclusion criteria were age >55 years and at least one of the following cardiovascular risk factors: arterial hypertension, diabetes mellitus, dyslipidemia, active smoking, and family history positive for coronary heart disease. The combined primary endpoint included total mortality, acute myocardial infarction (NSTEMI and STEMI), cardiopulmonary resuscitation, heart failure, and asystole or ventricular fibrillation during hospitalization. ECGs from 616 patients enrolled from 2006 to 2009 prior to noncardiac surgery in the No-Risk Study were analyzed. Results: The mean age was 67.6 (±8.1) years;300 (48.7%) patients were male. Fourteen (2.3%) patients suffered from the combined primary endpoint while in the hospital. In Kaplan-Meier analyses, a pathologic Q wave and QTc > 500 ms were significantly related to the incidence of the primary endpoint (p p = 0.042, respectively), whereas other ECG parameters such as LBBB, RBBB, PQ interval, QRS interval, and others were not related to worse in-hospital outcome. Conclusion: The 12-lead ECG is still an important diagnostic tool for perioperative risk assessment of cardiovascular events in noncardiac surgery in patients at risk.

关键词： ECG Perioperative Risk Cardiovascular Risk

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Effects of P301L-TAU on post-translational modifications of microtubules in human iPSC-derived cortical neurons and TAU transgenic mice

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Neural Regeneration Research 2025年第8期20卷 2348-2360页

作者： Mohamed Aghyad Al Kabbani christoph Köhler Hans Zempel Institute of Human Genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for Molecular Medicine Cologne(CMMC) University of CologneCologneGermany Center Anatomy Department ⅡMedical FacultyUniversity of CologneCologneGermany

TAU is a microtubule-associated protein that promotes microtubule assembly and stability in the *** is missorted and aggregated in an array of diseases known as *** are essential for neuronal function and regulated via a complex set of post-translational modifications,changes of which affect microtubule stability and dynamics,microtubule interaction with other proteins and cellular structures,and mediate recruitment of microtubule-severing *** impairment of microtubule dynamics causes neuronal dysfunction,we hypothesize cognitive impairment in human disease to be impacted by impairment of microtubule *** therefore aimed to study the effects of a disease-causing mutation of TAU(P301L)on the levels and localization of microtubule post-translational modifications indicative of microtubule stability and dynamics,to assess whether P301L-TAU causes stability-changing modifications to *** investigate TAU localization,phosphorylation,and effects on tubulin post-translational modifications,we expressed wild-type or P301L-TAU in human MAPT-KO induced pluripotent stem cell-derived neurons(i Neurons)and studied TAU in neurons in the hippocampus of mice transgenic for human P301L-TAU(p R5 mice).Human neurons expressing the longest TAU isoform(2N4R)with the P301L mutation showed increased TAU phosphorylation at the AT8,but not the p-Ser-262 epitope,and increased polyglutamylation and acetylation of microtubules compared with endogenous TAU-expressing neurons.P301L-TAU showed pronounced somatodendritic presence,but also successful axonal enrichment and a similar axodendritic distribution comparable to exogenously expressed 2N4R-wildtype-TAU.P301L-TAU-expressing hippocampal neurons in transgenic mice showed prominent missorting and tauopathy-typical AT8-phosphorylation of TAU and increased polyglutamylation,but reduced acetylation,of microtubules compared with non-transgenic *** sum,P301L-TAU results in changes in micr

关键词： human induced pluripotent stem cell microtubules P301L pR5 mice TAU tauopathy tubulin code

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Impact of concomitant use of proton pump inhibitors and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome

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Journal of Geriatric Cardiology 2016年第3期13卷 209-217页

作者： Yan YAN Xiao WANG Jing-Yao FAN Shao-Ping NIE Sergio Raposeiras-Roubin Emad Abu-Assi Jose P Simao Henriques Fabrizio D'Ascenzo Jorge Saucedo Jose R Gonzfilez-Juanatey Stephen B Wilton Wouter J Kikkert Ivlin Nufiez-Gil Albert Ariza-Sole Xian-Tao SONG Dimitrios Alexopoulos christoph liebetrau Tetsuma Kawaji Claudio Moretti Zenon Huczek Toshiharu Fujii Luis C Correia Masa-aki Kawashiril Sasko Kedev Beijing Anzhen Hospital Capital Medical University Beijing China University Hospital.4lvaro Cunqueiro Vigo Spain University Academic Medical Center Amsterdam the Netherlands Dipartimento di Scienze Mediche Divisione di Cardiologia. Citt& della Salute e della Scienza Turin Italy NorthShore University Hospital Chicago. USA University Clinical Hospital of Santiago de Compostela Spain Libin Cardiovascular Institute of Alberta Calgary Canada San Carlos Hospital Madrid Spain Bellvitge Hospital Barcelona Spain University Patras Hospital Athens Greece Kerckhoff Heart and Thorax Center Frankfurt Germany Graduate School of Medicine Kyoto University Kyoto Japan University Clinical Hospital Warsaw Poland Tokai University School of Medicine Tokyo Japan Hospital Sao RafaeL Salvador Brazil Kanazawa University Graduate School of Medicine Kanazawa Japan University Clinic of Cardiology Skopje Macedonia

Background There is great debate on the possible adverse interaction between proton pump inhibitors （PPIs） and clopidogrel. In ad- dition, whether the use of PPIs affects the clinical efficacy of ticagrelor remains less known. We aimed to determine the impact of concomi- tant administration of PPIs and clopidogrel or ticagrelor on clinical outcomes in patients with acute coronary syndrome （ACS） after percuta- neous coronary intervention （PCI）. Methods We retrospectively analyzed data fi＇om a ＂real world＂, international, multi-center registry between 2003 and 2014 （n = 15,401） and assessed the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on 1-year composite primary endpoint （all-cause death, re-infarction, or severe bleeding） in patients with ACS after PCI. Results Of 9429 patients in the final cohort, 54.8% （n = 5165） was prescribed a PPI at discharge. Patients receiving a PPI were older, more often female, and were more likely to have comorbidities. No association was observed between PPI use and the primary endpoint for patients receiving clopidogrel （ad- justed HR： 1.036; 95% CI： 0.903-1.189） or ticagrelor （adjusted HR： 2.320; 95% CI： 0.875-45.151）（Pinteraction = 0.2004）. Similarly, use of a PPI was not associated with increased risk of all-cause death, re-infarction, or a decreased risk of severe bleeding for patients treated with either clopidogrel or ticagrelor. Conclusions In patients with ACS following PCI, concomitant use of PPIs was not associated with in- creased risk of adverse outcomes in patients receiving either clopidogrel or ticagrelor. Our findings indicate it is reasonable to use a PPI in combination with clopidogrel or ticagrelor, especially in patients with a higher risk of gastrointestinal bleeding.

关键词： Acute coronary syndrome Clopidogrel Outcome Proton pump inhibitor Ticagrelor

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P2Y12受体抑制剂联合质子泵抑制剂对急性冠脉综合征患者缺血事件影响的临床分析

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中华医学杂志 2016年第33期96卷 2611-2615页

作者：冯斯婷严妍范婧尧王晓郑文聂绍平 Sergio Raposeiras-Roubin Emad Abu-Assi Jose P Simao Henriques Fabrizio D' Ascenzo Jorge Saucedo Jose R Conzalez-Juanatey Stephen B Wilton Wouter J Kikkert Ivan Nunez-Gil Albert Ariza-Sole Dimitrios Alexopoulos christoph liebetrau Tetsuma Kawaji Claudio Moretti Zenon Huczek Toshiharu Fujii Luis C Correia Masa-aki Kawashiri Sasko Kedev 首都医科大学附属北京安贞医院急诊危重症中心 100029 University Hospital Alvaro Cunqueiro Vigo Spain Academic Medical Center Amsterdam the Netherlands Dipartimento di Scienze Mediche Divisione di Cardiologia Citta della Salute e della Scienza Turin Italy North Shore University Hospital Chicago USA University Clinical Hospital of Santiago de Compostela Santiago de compostela Spain Libin Cardiovascular Institute of Alberta Calgary Canada San Carlos Hospital Madrid Spain Bellvitge University Hospital Barcelona Spain University Patras Hospital Athens Greece Kerckhoff Heart and Thorax Center Frankfurt Germany Graduate School of Medicine Kyoto University Kyoto Japan University Clinical Hospital Warsaw Poland Hospital Sao Rafael Salvador Brazil Kanazawa University Graduate School of Medicine Kanazawa Japan University Clinic of Cardiology Skopje Macedonia

目的本研究旨在分析P2Y12受体抑制剂联合质子泵抑制剂（PPI）治疗对经皮冠状动脉介入（PCI）术后的急性冠脉综合征患者缺血事件的影响。方法基于国际多中心回顾性注册登记研究，纳入2003至2014年因急性冠脉综合征人院行PCI术的患者，分... 详细信息

目的本研究旨在分析P2Y12受体抑制剂联合质子泵抑制剂（PPI）治疗对经皮冠状动脉介入（PCI）术后的急性冠脉综合征患者缺血事件的影响。方法基于国际多中心回顾性注册登记研究，纳入2003至2014年因急性冠脉综合征人院行PCI术的患者，分为PPI组及非PPI组并随访1年，主要临床终点为全因死亡／再发心肌梗死的复合终点。根据P2Y12受体抑制剂种类，将入组患者分为氯吡格雷组及替格瑞洛组，并比较不同药物与PPI联用发生临床终点事件的风险。结果研究入选9429例患者，PPI组占54．8％，具有更多高危因素。Cox回归结果提示PPI组较非PPI组全因死亡／再发心肌梗死复合事件的发生差异无统计学意义（HR1．00，95％CI 0．86—1．18）。根据P2Y12抑制剂种类不同分为氯吡格雷组和替格瑞洛组，不同P2Y12受体抑制剂联用PPI较未联用PPI患者的临床终点无差异，联用PPI的氯吡格雷组与替格瑞洛组的临床终点差异也无统计学意义。结论急性冠脉综合征患者PPI与P2Y12受体抑制剂联用不增加全因死亡和再发心肌梗死风险，尤其PPI联用氯吡格雷在患者的缺血事件上与替格瑞洛比较差异无统计学意义。

关键词：急性冠脉综合征氯吡格雷质子泵抑制剂患者结局评价替格瑞洛

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联合应用氯吡格雷和质子泵抑制剂对急性冠状动脉综合征患者经皮冠状动脉介入术后预后的影响

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中国医药 2017年第2期12卷 161-166页

作者：严研王晓范婧尧聂绍平 Sergio Raposeiras-Roubin Emad Abu-Assi Jose Paulo Simao Henriques Fabrizio D'Ascenzo Jorge Saucedo Jose Ramon Gonzalez-Juanatey Stephen B. Wilton Wouter J. Kikkert Ivan Nunez-Gil Albert Ariza-Sole Dimitrios Alexopoulos christoph liebetrau Testuma Kawaji Claudio Moretti Zenon Huczek Toshiharu Fujii Luis Claudio Correia Masa-aki Kawashiri Sasko Kedev 首都医科大学附属北京安贞医院急诊危重症中心 000029 西班牙比戈市阿尔瓦罗康克雷诺医院心内科 36312 荷兰阿姆斯特丹大学学术医学中心心内科 1105 意大利都灵市圣乔瓦尼巴蒂斯塔医院心内科 10126 美国芝加哥市北岸大学医院心内科 60201 西班牙圣地亚哥·德·孔波斯特拉大学临床医院心内科 15706 加拿大卡尔加里市阿尔伯塔利宾心血管研究所心脏科学医学科 T2N4N1 西班牙马德里市圣卡洛斯医院心内科 28040 西班牙巴塞罗纳市贝尔维尔医院心内科 08907 希腊雅典市佩特雷大学医院心内科 26504 德国法兰克福市基尔霍夫胸腔心脏中心心内科 61231 日本京都大学医学研究生院心内科 606-8507 波兰华沙市临床医院心内科 02-091 日本东京市东海大学医学院心内科 259-1193 巴西萨尔瓦多市圣拉斐尔医院 41253-190 日本金泽大学医学研究生院心内科 920-0942 马其顿斯科普里市临床心脏病诊所心内科 1000

目的探讨联合应用氯吡格雷和质子泵抑制剂（PPI）对急性冠状动脉综合征（ACS）患者经皮冠状动脉介入（PCI）术后预后的影响。方法回顾性分析2003年至2014年来自10个国家（加拿大，巴西，德国，波兰，荷兰，西班牙，意大利，希腊，中国... 详细信息

目的探讨联合应用氯吡格雷和质子泵抑制剂（PPI）对急性冠状动脉综合征（ACS）患者经皮冠状动脉介入（PCI）术后预后的影响。方法回顾性分析2003年至2014年来自10个国家（加拿大，巴西，德国，波兰，荷兰，西班牙，意大利，希腊，中国，日本）15个临床中心的ACS合并PCI术后18077例患者的临床资料。研究氯吡格雷、PPI与ACS患者PCI术后预后的关系。比较患者的基本临床特征、既往病史、生化指标、药物应用，以及终点事件的发生率情况。通过Cox回归模型进行分析及倾向性评分调整其他可能影响患者的预后因素包括人口学信息（年龄、性别）和临床指标，计算PPI这一干预因素的风险比并评价其是否能够明显影响患者的预后。结果基于国际多中心Blee MACs注册登记研究分析，排除关键数据缺失过多患者2676例。根据纳入与排除标准及倾向性评分调整整理后，再排除患者6461例，最终列队患者8940例。根据患者用药不同，将患者分为氯吡格雷＋PPI组（4814例）和氯吡格雷组（4126例）。氯吡格雷＋PPI组患者女性、高血压病史、高脂血症病史、糖尿病史、外周血管疾病史、既往急性心肌梗死史、慢性肾功能不全病史、消化道溃疡病史、冠状动脉旁路移植术病史、既往出血病史、恶性肿瘤病史、不稳定型心绞痛、非sT段抬高型心肌梗死、心功能Killip分级≥2级、经皮腔内冠状动脉成形术、出院后血管紧张素转换酶抑制剂／血管紧张素Ⅱ受体拮抗剂应用比例、年龄和入院时血肌酐水平明显高于氯吡格雷组[25．4％（1225／4814）比21．0％（865／4126）、59．9％（2882／4814）比49．2％（2032／4126）、48．3％（2327／4814）比42．7％（1762／4126）、26．4％（1272／4814）比22．1％（910／4126）、8．0％（386／4814）比5．6％（231／4126）、12．3％（593／4814）比10．6％（436／4126）、2．0％（98／4814）比0．7％（30／4126）、2．3％（112／4814）比1．0％（42／4126）、3．6％（172／4814）比2．2％（92／4126）、4．5％（219／4814）比3．0％（123／4126）、8．0％（387／4814）比4．7％（193／4126）、13．4％（644／4814）比9．1％（374／4126）、29．1％（1400／4814）比15．9％（656／4126）、14．5％（699／4814）比11．2％（462／4126）、56．0％（2697／4814）比55．7％（2300／4126）、75．5％（3633／4814）比68．6％（2829／4126）、（66±12）岁比（61±13）岁、（10±6）mg／L比（9±4）mg／L]；且入院时血红蛋白水平和出院后β受体阻滞剂应用比例明显低于氯吡格雷组[（138±19）g／L比（141±16）g／L、80．6％（3880／4814）比83．1％（3428／4126）]，差异均有统计学意义（均P〈0．05）。调整前，氯吡格雷＋PPI组主要终点事件（全因死亡／再发心肌梗死／出血）发生率明显高于氯吡格雷组，差异有统计学意义（风险比为1．331，95％置信区间为1．161-1．524）。调整后，氯吡格雷＋PPI组主要终点事件（全因死亡／再发心肌梗死／出血）发生率与氯吡格雷组比较，差异无统计学意义（风险比为1．036，95％置信区间为0．903-1．189）。结论ACS患者PCI术后联合应用PPI与氯吡格雷是合理的，尤其在胃肠道出血高危患者中。

关键词：急性冠状动脉综合征氯吡格雷质子泵抑制剂预后

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急性冠状动脉综合征患者经皮冠状动脉介入术后出血情况分析

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中国医药 2017年第6期12卷 801-805页

作者：严研王晓范婧尧聂绍平宋现涛 Sergio Raposeiras-Roubin Emad Abu-Assi Jose Paulo Simao Henriques Fabrizio D'Ascenzo Jorge Saucedo Jose Ramon Gonza1ez-Juanatey Stephen B. Wilton Ivan Nufiez-Gil Albert Ariza-Sole Dimitrios Alexopoulos [ christoph liebetrau Testuma Kawaji Zenon Huczek Toshiharu Fujii Luis Claudio Correia Masa-aki Kawashiri Sasko Kedev 首都医科大学附属北京安贞医院急诊危重症中心 100029 首都医科大学附属北京安贞医院心内科 100029 西班牙比戈市阿尔瓦罗康克雷诺医院心内科 36312 荷兰阿姆斯特丹大学学术医学中心心内科 1105 意大利都灵市圣乔瓦尼巴蒂斯塔医院心内科 10126 美国芝加哥市北岸大学医院心内科 60201 西班牙圣地亚哥·德·孔波斯特拉大学临床医院心内科 15706 加拿大卡尔加里市阿尔伯塔省利宾心血管研究所心脏科学医学科 T2N4N1 西班牙马德里市圣卡洛斯医院心内科 28040 西班牙巴塞罗纳市贝尔维尔医院心内科 08907 希腊雅典市佩特雷大学医院心内科 26504 德国法兰克福市基尔霍夫胸腔心脏中心心内科 61231 日本京都大学医学研究生院心内科 606-8507 日本东京市东海大学医学院心内科 259-1193 巴西萨尔瓦多市圣拉斐尔医院心内科 41253-190 日本金泽大学医学研究生院心内科 920-0942 马其顿斯科普里市临床心脏病诊所心内科 1000

目的分析急性冠状动脉综合征（ACS）经皮冠状动脉介入（PCI）术后出血情况。方法回顾性分析2003年1月至2014年12月来自11个国家16个临床中心的18077例行PCI的ACS患者的临床资料。根据是否出现出血事件，将患者分为出血组（558例）和非... 详细信息

目的分析急性冠状动脉综合征（ACS）经皮冠状动脉介入（PCI）术后出血情况。方法回顾性分析2003年1月至2014年12月来自11个国家16个临床中心的18077例行PCI的ACS患者的临床资料。根据是否出现出血事件，将患者分为出血组（558例）和非出血组（17519例），比较2组患者的基本临床特征、手术情况及生化指标。分析ACS患者PCI术后出血相关情况。结果马其顿中心数据因关键变量缺失过多而被排除患者2676例，故最终纳入10个国家15个中心15401例ACS患者。排除缺失数据，本研究共有12910例患者收集到出血部位的数据，409例患者存在出血事件。胃肠道是最常见出血部位，占48．7％（199／409），颅内出血占7．6％（31／409）。Logistic逐步回归方法多因素分析显示，既往出血病史、高血压病史是术后1年内消化道出血的危险因素。排除马其顿中心数据（2676例）与Cox回归模型和倾向性评分调整再排除5972例，剩余9429例作分层分析。根据是否联用质子泵抑制剂（PPI），将出院应用氯吡格雷生存患者8942例分为氯吡格雷联合应用PPI组（4814例）和氯吡格雷未联合应用PPI组（4126例）；将出院应用替格瑞洛生存患者489例分为替格瑞洛联合应用PPI组（351例）和替格瑞洛未联合应用PPI组（138例）。Kaplan-Meier法分析显示氯吡格雷联合应用PPI组1年出血事件发生率明显高于氯吡格雷未联合应用PPI组，差异有统计学意义（P=0．004）；替格瑞洛联合应用PPI组1年出血事件发生率与替格瑞洛未联合应用PPI组比较，差异无统计学意义（P=0．573）。结论ACS患者PCI术后最常见的出血部位为消化道，PPI与替格瑞洛联合应用在胃肠道出血风险较高患者中适用。

关键词：急性冠状动脉综合征出血质子泵抑制剂氯吡格雷替格瑞洛

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Achievements and Challenges in European Energy Markets

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Journal of Modern Power Systems and Clean Energy 2023年第3期11卷 698-704页

作者： christoph Weber University of Duisburg-Essen EssenGermany IEEE

The European electricity and gas markets have been deregulated more than two decades *** rather diverse starting points,they have continuously evolved over the years to accommodate with new challenges and to improve *** 2005,these markets have been complemented by the market for emission certificates established by the European Union(EU)emission trading *** partly competing paradigms have thereby shaped the markets and continue to drive their on-going transformation:effective competition,subsidiarity and sustainability.

关键词： Electricity marker Europe carbon pricing market design deregulation decarbonization sustainable energy system

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The evolutionary ecology of symbiont-conferred resistance to parasitoids in aphids

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Insect Science 2014年第3期21卷 251-264页

作者： christoph Vorburger Institute of Integrative Biology ETH Zǖrich Universitātstrasse 16 8092 Zǖdch EAWAG Swiss Federal Institute of Aquatic Science and Technology Uberlandstrasse 133 8600 Dǖbendoàf Switzerland

Aphids may harbor a wide variety of facultative bacterial endosymbionts. These symbionts are transmitted maternally with high fidelity and they show horizontal trans-mission as well, albeit at rates too low to enable infectious spread. Such symbionts need to provide a net fitness benefit to their hosts to persist and spread. Several symbionts haveachieved this by evolving the ability to protect their hosts against parasitoids. Reviewing empirical work and some models, I explore the evolutionary ecology of symbiont-conferredresistance to parasitoids in order to understand how defensive symbiont frequencies are maintained at the intermediate levels observed in aphid populations. I further show thatdefensive symbionts alter the reciprocal selection between aphids and parasitoids by augmenting the heritable variation for resistance, by increasing the genetic specificity of thehost-parasitoid interaction, and by inducing environment-dependent trade-offs. These effects are conducive to very dynamic, symbiont-mediated coevolution that is driven by frequency-dependent selection. Finally I argue that defensive symbionts represent a problem for biological control of pest aphids, and I propose to mitigate this problem byexploiting the parasitoids＇ demonstrated ability to rapidly evolve counteradaptations to symbiont-conferred resistance.

关键词： aphids biological control coevolution genotype × genotype interaction Hamiltonella defensa parasitoid resistance symbiosis

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