氯吡格雷抵抗的临床研究现状

氯吡格雷是一种血小板聚集(platelet aggregation,PA)抑制剂,其活性代谢产物可选择并不可逆地与血小板表面二磷酸腺苷(adenosine diphosphate,ADP)受体P2Y12结合,减少ADP结合位点,阻断ADP对腺苷酸环化酶的抑制作用,从而抑制PA。氯吡格雷可以有效预防动脉粥样硬化患者中缺血性事     

冠状动脉支架植入术后氯吡格雷低反应患者短期替格瑞洛强化治疗研究

目的：探讨经皮冠状动脉支架植入术（percutaneous coronary intervention,PCI）后氯吡格雷低反应（clopidogrel low response,CLR）患者短期替格瑞洛强化抗血小板治疗的临床疗效。方法：连续入选PCI术后经光学血小板聚集（light transmittance aggregation,LTA）法检出的CLR患者100例,随机分为氯吡格雷组（50例）和替格瑞洛组（50例）。氯吡格雷组予氯吡格雷75 mg/d;后者予替格瑞洛90 mg,2次/d,bid,强化1个月后改为氯吡格雷75 mg/d;两组患者均联合服用阿司匹林100 mg/d。治疗1个月后检测所有患者的血小板聚集率;随访6个月,比较两组心血管不良事件的发生情况。结果：两组患者随机治疗前二磷酸腺苷诱导的血小板聚集率（adenosine diphosphate?induced platelet aggregation,PLADP）及花生四烯酸诱导的血小板聚集率（arachidonic acid?induced platelet aggregation,PLAA）均无统计学差异（P > 0.05）;治疗1个月时,替格瑞洛组PLADP显著低于氯吡格雷组［（21.27 ± 12.81）% vs.（48.72 ± 10.92）%,P < 0.01］,两组患者PLAA无统计学差异（P > 0.05）;6个月时随访,替格瑞洛组心源性再入院患者显著低于氯吡格雷组（6% vs. 20%,P < 0.05）,但轻微出血增加（24% vs. 8%,P < 0.05）。结论：替格瑞洛的抗血小板聚集作用显著优于氯吡格雷,对CLR患者PCI术后替格瑞洛强化抗血小板治疗1个月可能减少心源性住院事件。     

氯吡格雷在经皮冠状动脉介入治疗中的应用进展

氯吡格雷是一种噻吩吡啶类衍生物,抑制由血小板表面二磷酸腺苷（adenosine diphosphate,ADP）受体所介导的血小板聚集[1],广泛用于临床血栓性疾病,是经皮冠状动脉介入（percutaneous coronary intervention,PCI）围术期的基础用药之一.     

冠心病患者氯吡格雷低反应性的研究

目的：探讨冠心病患者氯吡格雷低反应性（Clopidogrel low-responsive-ness,CLR）的发生率,并分析其临床特征。方法：选择90例入住我院的急性冠脉综合征患者,其中有27例行经皮冠状动脉介入治疗（PCI）,所有入选患者均给予氯吡格雷负荷剂量300 mg及维持量75 mg/d,于服用氯吡格雷前及服用氯吡格雷后7 d测定5μmol/L二磷酸腺苷（adenosine diphosphate,ADP）诱导的血小板聚集率,并计算血小板聚集抑制率（△A）。根据△A分为氯吡格雷低反应组和氯吡格雷正常反应组。结果：氯吡格雷低反应的发生率为24.4%。低反应组与正常反应组比较发现总胆固醇（total cholesterol,TC）、体重指数（body mass in-dex,BMI）、合并糖尿病及置入支架患者中差异有统计学意义。结论：CLR现象可能与TC、BMI、是否有糖尿病、是否置入支架等因素有关。     

光学比浊法与连续血小板计数法监测血小板聚集功能的比较

目的评价血小板功能检测仪PL-11应用的连续血小板计数方法 （PL-11）监测血小板功能的价值。方法通过光学比浊法（light transmittance aggregometry,LTA）与PL-11连续血小板计数法检测本院2012年26例服用氯吡格雷抗凝治疗的心血管病患者和45例健康志愿者的血小板聚集功能,分析两种方法相关性及差异。结果血小板聚集诱聚剂二磷酸腺苷（adenosine diphosphate,ADP）诱导的LTA与PL-11最大血小板聚集率（maximal aggregation ratio,MAR）存在较好相关性（r=0.766,P〈0.000 1）。分别用LTA与PL-11检测健康志愿者组、服药患者组,最大血小板聚集率均存在统计学差异（P〈0.000 1）。在两组人群中,LTA测得最大血小板聚集率范围均较PL-11广。PL-11在每例标本检测过程中,各测试点提供的平均血小板体积（mean platelet volume,MPV）变化趋势与检测期间血小板聚集率变化情况一致。结论 PL-11连续血小板计数法与＂金标准＂的光学比浊法检测血小板聚集功能时有较好的相关性,其应用价值可供临床及实验室参考。富血小板血浆标本与全血标本可能是两种方法检测结果差异的原因。     

冠心病血瘀证患者细胞色素P450 2C19＊17基因型分布与氯吡格雷治疗后血小板聚集率及出血风险的关系

目的：探讨细胞色素P450（cytochrome, CYP）2C19＊17等位基因变异对中国冠心病血瘀证患者经皮冠状动脉介入术（percutaneous coronary intervention, PCI）后应用氯吡格雷治疗的血小板聚集率及出血事件的影响。 方法：以限制性片段长度多态性聚合酶链反应基因分析方法检测CYP2C19＊17基因多态性,研究2009年7月至2011年4月福建省立医院心内科择期进行PCI成功的冠心病血瘀证患者520例。PCI术前常规服用阿司匹林300 mg、氯吡格雷300 mg。术前采血,制备富血小板血浆、贫血小板血浆及二磷酸腺苷（adenosine diphosphate, ADP）诱导剂,采用比浊法,以最终浓度为5 μmol/L ADP为诱导剂,在氯吡格雷治疗前及治疗后10 d,检测血小板聚集率。分析最大血小板聚集率（maximal aggregation, Aggmax）和残余血小板聚集率（5-min aggregation, Agglate）。 结果：试验发现有5.96%的患者发生心肌梗死血栓溶解术出血事件,而本试验中病人的CYP2C19＊17等位基因频率为7.98%。对于CYP2C19＊17等位基因携带者,其出血事件发生率远高于野生型（P＜0.01）;在基线水平,5 μmol/L ADP诱导的Aggmax和Agglate以及血小板聚集率在CYP2C19＊17各基因型之间并没有显著区别;然而经氯吡格雷治疗10 d后,CYP2C19＊17等位基因携带者与野生型相比,上述3项指标均明显降低（P＜0.01或P＜0.05）,血小板聚集抑制率显著高于野生型患者（P＜0.01）;携带有CYP2C19＊17等位基因的患者与野生型相比,具有更高的出血风险（P＜0.01）。 结论：冠心病血瘀证患者CYP2C19＊17等位基因携带者有着显著的氯吡格雷反应性且其出血风险明显增加。     

PL-11两种诱导剂监测健康人服用氯吡格雷后的血小板功能变化

目的：评价新型血小板功能检测方法PL-11两种诱导剂对氯吡格雷短期效应的监测。方法与以二磷酸腺苷（adenosine diphosphate,ADP）诱导的光比浊法（ADP-LTA）为参照,比较ADP（ADP-PL-11）与胶原（Col-PL-11）诱导的PL-11对健康人服用氯吡格雷后血小板功能变化的监测。结果25名健康青年男性平均年龄（27.5±3.7）岁,服药6 d后,血小板功能均有所降低。Col-PL-11在基础值范围64.7%-83.6%（95%PI）,ADP-LTA结果在基础值范围是65.9%-89.1%（95%PI）,ADP-PL-11为67.2%-86.8%（95%PI）。服药前后Col-PL-11结果存在部分重叠区域。各方法相关性分别为ADP-PL-11 vs LTA, r=0.757,P＜0.001;ADP-PL-11 vs Col-PL-11,r=0.764,P＜0.001;Col-PL-11 vs LTA,r=0.521,P=0.009。以ADP活化LTA结果在服药后比服药前基础值降低至少10%（＞10%）为氯吡格雷低反应性的标准,ROC分析得到ADP-PL-11（临界值66%）敏感度和特异性分别为84.6%,88.2%;Col-PL-11（60.0%）敏感度和特异性分别为69.2%,70.6%。结论 PL-11检测氯吡格雷治疗时ADP比胶原具有较高的敏感度,ADP-LTA与ADP-PL-11之间结果可能存在可交换性,使ADP激活的PL-11检测可能成为替代经典光比浊法的血小板功能监测方法。     

急性冠脉综合征患者氯吡格雷低反应与短期临床观察

目的检测急性冠脉综合征（Acutecoronary syndrome,ACS）患者服用氯吡格雷治疗前后二磷酸腺苷（Adenosine diphosphate,ADP）诱导的血小板聚集率变化,同时观察氯吡咯雷低反应对ACS临床主要心血管事件（MACE）发生率的影响。方法 342名ACS患者服用氯吡格雷前与服用24h后ADP诱导的血小板聚集率,按照血小板聚集率的抑制程度分为低反应组和正常反应组。同时观察两组患者1个月内MACE发生率（包括：心源性死亡、非致死性心肌梗死、卒中、心绞痛）和出血并发症。结果发生氯吡格雷低反应的患者54例（15.8%）,氯吡格雷正常的患者288例（84.2%）。主要心血管事件发生26例（7.6%）,其中氯吡格雷低反应组为11例（20.4%,11/54）,正常反应组为15例（5.2%,15/288）,两组存在显著差异（P=0.001）。结论口服氯吡格雷对血小板聚集率的抑制程度存在明显的个体差异,与正常反应组相比,氯吡格雷低反应组MACE的发生率明显增高。     

不同抗血小板治疗对急性脑梗死患者血小板活化聚集状态的比较

目的:探讨不同抗血小板治疗对脑梗死急性期患者血小板活化及聚集状态的影响?方法:97例脑梗死患者随机入组不同的抗血小板治疗组(阿司匹林治疗组?氯吡格雷治疗组?阿司匹林联合氯吡格雷治疗组),在入院第1天(治疗前)和第10天采用流式细胞仪检测血小板CD62P?比浊法检测花生四烯酸(arachidonic acid,AA)诱导的血小板最大聚集率(MARAA)和二磷酸腺苷(adenosine diphosphate,ADP)诱导的血小板最大聚集率(MARADP)?结果:3组患者入院第1天CD62P?MARAA?MARADP无显著差异,治疗10 d后3组的CD62P?MARAA?MARADP值均下降,与入院第1天的CD62P?MARAA?MARADP值比较,差异有统计学意义?3组脑梗死患者血小板MARADP下降程度组间比较有差异,氯吡咯雷治组MARADP下降明显,阿司匹林联合氯吡格雷治疗组下降更明显?血小板MARAA?血小板CD62P下降程度组间比较无显著差异?结论:阿司匹林?氯吡格雷?阿司匹林联合氯吡格雷3种抗血小板治疗方法均能有效减少脑梗死急性期的血小板活化,降低血小板最大聚集率,提示临床治疗均有效;氯吡格雷和阿司匹林联合治疗更能抑制血小板的聚集,抗血小板疗效更好?     

冠心病患者白细胞miR-223-3p水平与氯吡格雷治疗后的血小板反应无关

目的：探讨冠心病患者白细胞miR-223-3p水平与氯吡格雷治疗后血小板反应之间的潜在相关性。方法：收 集188名择期经皮冠状动脉介入治疗(percutaneous coronary intervention,PCI)术后接受双重抗血小板治疗的门诊患者的 一般资料和血标本,检测二磷酸腺苷(adenosine diphosphate,ADP)诱导的全血血小板聚集率。选取血小板反应有显著 差异的患者(超反应组和无反应组),检测其白细胞miR-223-3p水平。结果：除ADP诱导的全血血小板聚集率外,两组 患者的一般资料和白细胞miR-223-3p水平差异无统计学意义(P>0.05)。结论：冠心病择期PCI术后门诊患者外周血白细 胞miR-223-3p水平与氯吡格雷治疗后的血小板反应无关。     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

APPLICATION OF LORNOXICAM TO PATIENT-CONTROLLED ANALGESIA IN PATIENTS UNDERGOING ABDOMINAL SURGERIES

FOR anesthesiologis s ,treatingpostoperativepainhas alwaysbeen a problem.Althoughopioidshave been provedtobe effective,theirsideeffectscouldnotbeignored.With thedevelopmentofscienceand pharmacology,many drugs with aspectsof satisfactoryanalgesicefficacyand couldbe welltoleratedby patientshave been developed.And lornoxicamisone of them, which isa non-steroidalanti-inflammatorydrug (NSAID ), with analgesic, anti-infl-ammatory,andantipyreticproperties.Itseliminationhalf-time(3 to 5 hours) isle…     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

目的：评价使用安心颗粒对急诊经皮冠状动脉介入术（PPCI）术后生活质量的影响.方法：将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组（术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次）和对照组（仅接受基础药物治疗）.所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表（MIDAS）、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果：入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异（P＞0.05）;出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低（P＜0.05）;组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低（P＜0.05）.两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血（P＞0.05）.两组发生轻度血小板减少症的患者数比较无差异（P＞0.05）.结论：PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.     

The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function, atrio-ventricular node function and hemodynamics

Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P＜0.01);the MAP decreased(P＜0.01)and the HR increased drastically(P＜0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.     

Dynamic Changes in Serum Estradiol and Progesterone levels in Patients of Premenstrual Syndrome with Adverse Flow of Liver-qi

Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.     

Real-time Three-dimensional Echocardiography in Assessment of Left Ventricular and Right Ventricular Volumes

Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.     

SCREENING FOR A 21-CHROMOSOME ABNORMALITY IN PREIMPLANTED EMBRYOS OF ELDERLY WOMEN

Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.     

Scientific principles and rigorous processes should be followed in developing clinical guidelines for therapeutic interventions of integrative medicine

A clinical guideline for the therapeutic interventions of integrative medicine may be defined as a written document which states a series of recommendations on therapeutic interventions of integrative medicine for a special disease or condition. The guideline may provide assistance to medical professionals in making clinical decisions aimed at improving the clinical outcome of patients and reducing the costs of medical care（~＇4~. Recommendations issued by a guideline should be based on the best available evidence in both Western and Chinese medicine. For fulfilling this purpose, the development of clinical guidelines for therapeutic interventions in the field of integrative medicine should follow scientific principles and undergo a rigorous processes.