CYP2C19基因多态性对老年冠心病PCI术后抗血小板治疗的影响

目的探讨中国南方汉族人中CYP2C19基因多态性与冠心病(CHD)氯吡格雷治疗后血小板活性的关系。方法选取拟行冠脉介入术治疗的中国南方汉族老年CHD患者193例,均给予氯吡格雷300 mg负荷剂量,75 mg qd维持剂量。通过流式细胞仪检测血小板聚集率,采用聚PCR RFLP法基因型进行CYP2C19基因型检测。根据不同的基因型人群间氯吡格雷的药物代谢动力学特征把携带野生型基因(*1/*1)归为快代谢型,突变杂合型(*1/*2、*1/*3)为中间代谢型、突变纯合型(*2/*2、*2/*3、*3/*3)为慢代谢型。观察患者在服用氯吡格雷等药物治疗后7 d及14 d血小板聚集率的情况。结果野生型与中间代谢型、慢代谢型组间血小板聚集程度比较差异有统计学意义(P0.05)。中间代谢型、慢代谢型7 d组血小板活性降低程度显著优于7 d组,患者CYP2C19基因慢代谢型的比例为9.84%;心血管事件占8.08%,与野生型基因患者相比有差异(P0.05)。结论 CYP2C19基因突变与CHD PCI术后氯吡格雷治疗血小板活性有关。     

细胞色素P4502 C19快代谢基因型缺血性卒中患者氯吡格雷抵抗的影响因素分析

目的 探讨细胞色素P4502C19(CYP2C19)快代谢基因型缺血性卒中患者氯吡格雷抵抗的影响因素.方法 回顾性连续纳入CYP2C19快代谢基因型(CYP2C19*1/*1)缺血性卒中住院患者204例,均于确诊后连续服用氯吡格雷75 mg/d,共7 d,第8天晨起空腹抽取静脉血,2 h内完成血栓弹力图血小板图的检测....     

CYP2C19基因多态性与冠心病患者PCI术后氯吡格雷抵抗的关系

目的:探讨CYP2C19基因多态性对冠心病患者经皮冠状动脉介入治疗(PCI)术后氯吡格雷抵抗(CR)的影响。方法:选择在我院接受治疗并进行PCI手术的冠心病患者100例,其中CR 24例,无氯吡格雷抵抗(NCR)76例。根据CYP2C19基因型,患者被分为快代谢型CYP2C19*1/*1 (49例),中间代谢型CYP2C19*1/*2(28例)和*1/*3 (11例),慢代谢型CYP2C19*2/*2 (9例)和*2/*3 (3例)。分析不同基因型与CR、最大血小板聚集率(MPA)、主要不良心血管事件(MACE)发生的关系。结果:以快代谢型CYP2C19*1/*1基因型为基础,中间代谢型CYP2C19*1/*2和*1/*3 (OR=4.16、5.03,P均0.05)及慢代谢型CYP2C19*2/*2和*2/*3 (OR=7.04、17.6,P均0.01)发生CR的风险显著增加,中间代谢型分别增加4.16和5.03倍,慢代谢型分别增加7.04和17.60倍;与快代谢基因型比较,中、慢代谢基因型的MPA和MACE发生率均显著增加(P0.05或0.01);CR组MACE发生率显著高于NCR组(20.8%比5.3%,P=0.02)。结论:CYP2C19基因多态性对冠心病患者PCI术后氯吡格雷抵抗有一定的影响,带有中、慢代谢基因型冠心病患者更易发生氯吡格雷抵抗以及有更高的最大血小板聚集率和主要不良心血管事件发生率。     

细胞色素P4502C19基因多态性对NSTE-ACS患者血小板反应性及临床预后的影响

目的探讨细胞色素P450 2C19(CYP2C19)基因多态性与非ST段抬高急性冠脉综合征(NSTE-ACS)患者服用氯吡格雷后血小板反应性的关系,并评价不同基因型对NSTE-ACS患者预后的影响。方法连续纳入接受PCI治疗的NSTE-ACS患者462例,依据CYP2C19基因型,分为快代谢型(CYP2C19*1/*1)、中间代谢型(CYP2C19*1/*2、CYP2C19*1/*3)和慢代谢型(CYP2C19*2/*2、CYP2C19*2/*3)。采用流式细胞术测定的血小板反应指数(PRI)和光比浊法测定的血小板聚集率(PAG)两种方法来评价患者在服用氯吡格雷后的血小板反应性。全部患者随访2年,以全因死亡、支架内再狭窄、急性支架内血栓形成、再发急性心肌梗死定义为主要不良心血管事件(MACE),采用Cox回归分析评价CYP2C19基因型、PRI、PAG等指标对MACE的预测能力。结果快代谢型158例、中间代谢型246例、慢代谢型58例。快代谢型、中间代谢型、慢代谢型PRI分别为48.6±10.5、56.7±12.6、65.3±11.4,PAG分别为67.4±8.5、71.9±8.2、7...     

北京地区汉族冠心病患者CYP2C19基因多态性的研究分析

目的:探讨北京地区汉族冠心病患者细胞色素P450(CYP)2C19基因多态性的分布特征及其与氯吡格雷抵抗、支架内血栓的相关性。方法:入选800例无亲缘关系的冠心病患者,检测其CYP2C19基因型,和ADP诱导的血小板聚集率,确定是否存在氯吡格雷抵抗(CR),并分为CR组(215例),NCR组(585例),比较两组携带基因型及冠脉支架内血栓发生率。结果:CYP2C19分为三种表型,快代谢型(基因型为CYP2C19*1/*1)、中间代谢型(基因型为CYP2C19*1/*2和*1/*3)、慢代谢型(基因型为CYP2C19*2/*2、*2/*3)。入选冠心病患者携带快代谢型*1/*1(41.6%),中间代谢型*1/*2,*1/*3(46.8%)较多,以中间代谢型显著较多;CR组215例,即氯吡格雷抵抗发生率为26.9%(215/800)。与NCR组比较,CR组患者携带快代谢型基因型*1/*1(43.9%比35.3%)明显减少,而携带慢代谢型基因型*2/*2,*2/*3(9.9%比17.2%)明显较多(P0.05或0.01)。本研究中共有15例(1.88%)发生确定的支架内血栓,其中10例(4.65%)为CR组,5例(0.85%)为NCR组,即CR组的支架内血栓事件率显著高于NCR组(P0.01)。结论:北京地区汉族冠心病患者携带P450(CYP)2C19基因中间代谢型最多;氯吡格雷抵抗发生率26.9%,CR组携带慢代谢型基因型显著多于NCR组;CR组的支架内血栓事件率显著高于NCR组。     

冠心病介入术后病人CYP2C19基因多态性与血小板抑制率的关系探讨

目的探讨冠心病介入术后服用氯吡格雷病人CYP2C19基因多态性与二磷酸腺苷(ADP)诱导的血小板抑制率之间的关系。方法入选2015年9月—2016年4月因冠心病(CHD)就诊并成功进行经皮冠状动脉介入术(PCI)的病人132例,最终纳入符合条件的病人124例。根据CYP2C19基因型将病人分为氯吡格雷正常、中间和慢代谢型3组。并采用改良血栓弹力图(TEG)法测定二磷酸腺苷(ADP)诱导的血小板抑制率及ADP的MA值(MA-ADP)。分析3组病人的临床资料(一般情况、合并疾病、血脂及肌酐水平),CYP2C19基因型与ADP抑制率及MA-ADP之间的相关性。结果超快代谢病人(CYP2C19*1/*17)1例(0.8%),正常代谢病人(CYP2C19*1/*1)43例(34.5%),中间代谢型(CYP2C19*1/*2、CYP2C19*1/*3)56例(45.2%),慢代谢病人(CYP2C19*2/*2、CYP2C19*2/*3)24例(19.4%)。3组病人在性别、年龄、高血压、糖尿病、吸烟、总胆固醇(TC)及肌酐(Cr)水平方面差异均无统计学意义(P0.05),低密度脂蛋白(LDL)、高密度脂蛋白(HDL)及体重指数(BMI)比较差异有统计学意义(P0.05)。3组病人氯吡格雷低反应性(LCR)发生率比较差异无统计学意义(χ~2=1.670,P0.05);3组病人MA-ADP47 mm发生率比较无统计学意义(χ~2=1.883,P0.05)。结论CYP2C19基因型与ADP抑制率及MA-ADP之间无明显相关性,但与BMI可能存在一定相关性。     

CYP2C19指导ACS行PCI患者抗血小板药物选择的研究

目的:根据急性冠状动脉综合征(ACS)行经皮冠状动脉介入治疗(PCI)患者CYP2C19基因型的不同选择抗血小板药物及剂量进行治疗,观察其抗血小板效应及出血风险,为个体化抗血小板药物的选择提供参考。方法:入选231例行PCI的ACS患者并检测其CYP2C19基因型,根据基因型的不同分为快代谢组(CYP2C19*1/*1)、中代谢组(CYP2C19*1/*2、CYP2C19*1/*3)、慢代谢组(CYP2C19*2/*2、CYP2C19*3/*3、CYP2C19*2/*3),并分别给予快代谢组常规双联抗血小板治疗(氯吡格雷75mg qd+阿司匹林100mg qn),中代谢组氯吡格雷剂量加倍(氯吡格雷150mg qd+阿司匹林100mg qn),慢代谢组换用新型抗血小板药物(替格瑞洛90mg bid+阿司匹林100mg qn),比较各组用药3个月后血小板抑制率变化情况及出血事件的发生情况。结果:根据基因型所分3组的临床基线资料及PCI结果无统计学差异。中代谢组及慢代谢组患者用药3个月后,血小板抑制率均较快代谢组血小板抑制率升高,慢代谢组血小板抑制率较中代谢组明显升高,差别具有统计学意义(均P0.05)。结论:PCI术后的ACS患者中,携带CYP2C19*2、CYP2C19*3等位基因的高危患者,采用氯吡格雷剂量加倍及换用替格瑞洛均可充分抑制血小板,且换用替格瑞洛优于氯吡格雷剂量加倍。     

沈阳地区汉族人群CYP2C19基因代谢型分布及临床用药指导

目的研究沈阳地区汉族人群中氯吡格雷基因代谢型的分布情况,以指导临床用药。方法收集2016年9月—2017年8月于沈阳医学院附属第二医院体检及住院的病人96例,应用多重荧光定量PCR探针法对其CYP2C19的基因多态性进行检测,研究氯吡格雷基因代谢型的分布情况,根据其对抗血小板聚集药物氯吡格雷的药物敏感性,为病人提供用药指导。结果本研究共检测到7种基因型,分别为:*1/*1(38.54%),*1/*2(33.33%),*2/*2(14.58%),*1/*3(7.29%),*2/*3(2.08%),*1/*17(3.12%),*2/*17(1.04%),其中CYP2C19*1位点突变占60.4%,CYP2C19*2位点突变占32.8%,CYP2C19*3位点突变占4.7%,CYP2C19*17位点突变占2.1%。4种代谢型:慢代谢型(*2/*2,*2/*3,*3/*3)占16.7%,中等代谢型(*1/*2,*1/*3,*2/*17,*3/*17)占40.6%,快代谢型(*1/*1)占38.5%,超快代谢型(*1/*17,*17/*17)占4.2%。结论 CYP2C19中,慢代谢型病人所占比例高,鉴于*2、*3基因携带者在植入支架后再形成血栓的风险高,对拟行经皮冠状动脉介入治疗(PCI)术并用氯吡格雷治疗的病人,进行个体化的CYP2C19基因检测,具有十分重要的临床意义。     

冠心病介入治疗术后服用氯吡格雷患者的CYP2C19基因型与血小板抑制率的关系研究

目的探讨服用氯吡格雷的冠心病介入术后患者的CYP2C19基因型与二磷酸腺苷(ADP)诱导的血小板抑制率之间的关系。方法选取冠心病介入治疗术后服用氯吡格雷的患者500例,根据CYP2C19基因型分为氯吡格雷快、中、慢代谢3组,通过血栓弹力图测定ADP诱导的血小板抑制率;分析3组CYP2C19基因型与血小板抑制率之间的相关性;对患者进行术后6个月的随访,观察心血管不良事件发生率。结果 (1)500例患者中,氯吡格雷快、中、慢代谢3组的人群分布为42.0%、44.8%和13.2%。(2)氯吡格雷快代谢组的血小板抑制率在0~20%、20%~50%、50%~75%和75%~100%的人群分布为1.90%、14.29%、30.00%和53.81%;中代谢组的人群分布为3.57%、17.86%、22.32%和56.25%;慢代谢组的人群分布为7.58%、21.21%、30.30%和40.91%;3组之间ADP诱导的血小板抑制率差异无统计学意义(P>0.05)。(3)随访6个月,氯吡格雷快、中、慢代谢3组发生心血管缺血事件分别有9、13和4例,3组之间的缺血性心血管事件差异无统计学意义(P>0.05)。结论在本组人群中,CYP2C19基因型与氯吡格雷血小板抑制率之间无明显相关性,推测仅通过CYP2C19基因型不能准确预测氯吡格雷抵抗。     

CYP2C19基因多态性与PCI手术患者血小板抑制率的相关性研究

目的 研究CYP2C19基因多态性对经皮冠状动脉介入治疗（PCI）手术患者血小板抑制率的影响。方法 本研究纳入符合入选标准的2014年1月至2016年4月在解放军第一七五医院心内科住院的冠心病患者210例,均需行PCI手术治疗。所有入选者均采取静脉血标本并提取外周血基因组DNA,进行PCR 扩增及纯化,进行基因芯片杂交显色,通过生物芯片识读仪检测CYP2C19基因型,根据不同的基因型对患者进行分组。入选者服用负荷量阿司匹林+氯吡格雷24 h后采取静脉血标本,然后用血栓弹力图仪（TEG）检测并自动计算出二磷酸腺苷（ADP）诱导的血小板抑制率。结果 入选的210例患者各基因型比例分别为：（*1/*1）94例（44.8%)、（*1/*2）79例（37.6%）、（*1/*3）12例（5.7%）、（*2/*2）20例（9.5%）、（*2/*3）4例（1.9%）、（*3/*3）1例（0.5%）,其中快代谢型（EM型）94例（44.8%）、中等代谢型（IM型）91例（43.3%）、慢代谢型（PM型）25例（11.9%）,共有43例患者（20.5%）出现氯吡格雷抵抗现象（CR）。不同基因型组患者的血小板抑制率差异均有统计学意义（P<0.01）,其中PM型患者的血小板抑制率最低,IM型次之;不同基因型组患者的氯吡格雷抵抗情况差异有统计学意义（P<0.01）,其中PM型患者的CR远高于另外两组。结论 CYP2C19不同基因型对氯吡格雷抗血小板作用的影响存在显著差异,其中携带CYP2C19 *2或*3突变等位基因的PCI手术患者发生CR的风险明显增加。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.