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摘要： 替格瑞洛是一种新型P2Y12受体拮抗剂,具有起效快、作用强、无需肝脏代谢激活及可逆性抑制血小板聚集等优势。研究证实,替格瑞洛对氯吡格雷抵抗的缺血性脑卒中患者疗效较好,尤其在双联抗血小板治疗中表现出更低的脑卒中复发风险,且严重出血风险未显著增加。本文围绕替格瑞洛的作用机制及其在急性缺血性脑卒中的应用研究进展进行综述,以期为临床上替格瑞洛的应用提供参考。
关键词: 替格瑞洛 ；急性缺血性脑卒中 ；血小板 ；动脉粥样硬化 ；随机对照试验 ；指南
摘要： Professor LUO Guoan,a professor at Tsinghua University,is the director of the Network Center(Ministry of Education,PRC)for Collaborative Study of TCM Modernization.His main research areas include pharmaceutical analysis,modernization of traditional Chinese medicine(TCM),and systems biology for TCM.Currently,his research focuses on organ-on-a-chip,organoid-on-a-chip,and drug sensitivity screening and automated platform for tumor organoid.As one of the pioneers of microfluidic technology in China,Prof.Luo has led his research team in conducting research on microfluidic technology in the field of biomedicine for more than 20 years.They have successfully established a highly integrated and automated bio-mimetic microfluidic chip experimental platform,and developed various new models of microfluidic organ-on-a-chip.These contributions have provided reliable experimental platforms and in vitro models for the evaluation of drug efficacy and safety.Prof.Luo is also dedicated to applying modern pharmaceutical analysis techniques and multidisciplinary approaches from life sciences to the study of complex systems of TCM.He has founded and developed a series of theoretical and technical frameworks for the analysis of TCM and the modern research of TCM formulas,including fingerprints of traditional Chinese medicines,Chemomics,and TCM integrative systems biology,thereby advancing the modernization of TCM research.His research achievements have been awarded the National Science and Technology Progress Second Prize four times,and multiple provincial and ministerial-level science and technology progress or natural science awards.
关键词: thereby ；conducting ；modernization
摘要： 抗栓治疗是预防急性缺血性卒中复发的关键手段。随着多组学研究的进展和越来越多影响药物安全性和有效性的相关基因被发现,药物基因组学在个体化治疗中的应用逐渐受到关注。本文阐述了药物基因组学在急性缺血性卒中患者抗栓治疗中的指导作用的研究进展,旨在挖掘通过基因检测优化药物选择与剂量调整的潜力。研究表明,氯吡格雷等药物的疗效因细胞色素P450酶家族2亚家族C成员19(cytochrome P450 family 2 subfamily C member 19,CYP2C19)基因多态性而异,携带CYP2C19*2或CYP2C19*3等功能缺失等位基因的患者对标准抗血小板治疗反应较差,不能有效降低卒中复发风险,但通过基因检测指导药物选择可以显著提高治疗效果。此外,心源性卒中患者目前常选择华法林或新型口服抗凝药作为主要的抗栓治疗选择。华法林的剂量效应与多个基因,如细胞色素P450酶家族2亚家族C成员9(cytochrome P450 family 2 subfamily C member 9,CYP2C9)和维生素K环氧化物还原酶C1(vitamin K epoxide reductase complex 1,VKORC1)的多态性密切相关。基因检测能够帮助医师个体化调整华法林剂量,减少出血或血栓事件的发生。综上所述,药物基因组学在急性缺血性卒中抗栓治疗中的应用为个体化治疗提供了新的思路,未来有望进一步提高治疗的安全性和有效性。
关键词: 急性缺血性卒中 ；药物基因组学 ；个体化治疗 ；抗栓治疗
被引量
1
摘要： 目的:为新型抗血小板药物的研发提供参考。方法:以“抗血小板”“血小板黏附”“血小板活化”“血小板聚集”“作用机制”“Antiplatelet”“Platelet adhesion”“Platelet activation”“Platelet aggregation”“Mechanism”等为中英文关键词,在中国知网、万方数据、PubMed等数据库中组合查询2003年1月-2020年2月发表的相关文献,就血小板参与血栓形成过程中各个级联反应相关的重要信号通路及其作用,以及以各个分子信号为靶点的药物研究进展进行综述。结果与结论:共检索到相关文献3863篇,其中有效文献52篇。目前,抗血小板药物作用靶点包括血小板黏附信号靶点[如膜糖蛋白(GP)Ⅰb-Ⅸ-Ⅴ与血管性血友病因子的相互作用、GPⅥ与胶原的相互作用]、血小板活化信号靶点[二磷酸腺苷(ADP)受体通路、磷酸二酯酶相关信号、磷脂酰肌醇-3-激酶信号、血栓素相关信号)、血小板聚集靶点[GPⅡb/Ⅲa、蛋白酶激活受体]、磷脂酶C、P-选择素、血小板活化因子等。这些靶点和信号通路参与了血小板黏附、激活、聚集过程以及促进了血小板相关血栓的形成,许多作用于上述靶点的抗血小板药物被研发,包括卡普赛珠单抗、西洛他唑、氮吡格雷等。现有抗血小板药物或在动物实验阶段,或在临床试验阶段,仅有部分药物被批准用于临床。
关键词: 抗血小板 ；血小板黏附 ；血小板激活 ；血小板聚集 ；药物研发 ；作用靶点
被引量
24
摘要： 替格瑞洛是一种新型的P2Y12受体拮抗剂,可与血小板P2Y12受体可逆结合,主要经细胞色素P450酶3A4(CYP3A4)代谢,口服后可迅速产生血小板抑制作用,是治疗急性冠状动脉综合征(ACS)的重要药物之一。与其他噻吩吡啶类(氯吡格雷、普拉格雷)抗血小板药物临床获益不同之处在于,替格瑞洛的某些临床特征独立于P2Y12受体拮抗作用。替格瑞洛还可抑制平衡核苷转运体1(ENT1),从而抑制细胞内腺苷摄取,增加腺苷半衰期及血浆腺苷浓度水平,发挥保护心肌细胞、增加冠状动脉灌注血流、抑制血小板聚集等等作用。随着腺苷浓度的升高,也会引起一些如呼吸困难、肌酐和尿酸水平的升高、心动过缓等不良反应。本文将对替格瑞洛对腺苷的影响及其所产生的生物学效应的研究进展进行综述。
关键词: 替格瑞洛 ；腺苷 ；生物学效应
被引量
6
摘要： 铜离子导致细胞死亡是一种铜依赖性且独特的细胞死亡,与其他现有的形式的细胞死亡不同。长期以来,铜诱导的细胞死亡是否可以导致细胞死亡及其导致细胞死亡的机制一直存在争议,直到最近的研究铜死亡cuproptosis的机制被发现。在那之后,越来越多的研究人员试图确定cuproptosis与癌症过程之间的关系。因此,在这篇综述中,我们系统地详细介绍了铜离子在人类的全身和细胞代谢过程,以及铜离子在肿瘤中的作用。其次,讲明了cuproptosis的发现过程及其机制,还概述了cuproptosis及其关键基因FDX1与癌症之间的关联,及FDX1与现有的肿瘤药物相互作用的新进展。Cell death caused by copper ions is a copper-dependent and unique cell death that is different from other existing forms of cell death. For a long time, whether copper-induced cell death can lead to cell death and the mechanism by which it leads to cell death have been controversial until recent studies have discovered the mechanism of copper death cuproptosis. Since then, more and more researchers have tried to determine the relationship between cuproptosis and cancer processes. Therefore, in this review, we systematically and in detail introduce the systemic and cellular metabolic processes of copper ions in humans, as well as the role of copper ions in tumors. Secondly, the discovery process and mechanism of cuproptosis are explained, and the association between cuproptosis and its key gene FDX1 and cancer is also outlined, as well as new progress in the interaction between FDX1 and existing tumor drugs.
关键词: 肿瘤 ；铜死亡 ；FDX1
摘要： 脑梗死的发病率和致死率极高,其病因主要是动脉粥样硬化性脑血栓形成,抗血小板治疗是动脉粥样硬化性脑梗死急性期及二级预防的重要环节。阿司匹林和氯吡格雷是目前在临床应用最为广泛的抗血小板药物,但是抗血小板聚集作用在不同个体间存在较大差异,部分人群对于抗血小板药物的反应性较低,称为抗血小板药物抵抗。文中阐述了导致阿司匹林和氯吡格雷抵抗的主要机制以及临床上针对此种现象所采取的治疗措施,旨在为脑梗死患者的个性化治疗提供参考。
关键词: 阿司匹林 ；氯吡格雷 ；抵抗 ；机制 ；治疗
被引量
103
摘要： 甲型流感病毒因其高变异性和传播能力,能够引起全球性的大流行。目前,抗流感病毒药物是临床治疗流感的主要手段,这些药物通过阻断病毒的进入、复制和释放等环节发挥抗病毒作用。然而,流感病毒的变异和逃避免疫系统的能力促使科研人员不断分析新的甲型流感抗病毒药物。扎那米韦是一种有效的神经氨酸酶抑制剂,通过抑制病毒从宿主细胞中释放,从而限制其在体内的传播。随着流感病毒的不断变异和耐药性的增加,单一药物的治疗方案已经不足以应对当前的流感挑战。因此,开发与扎那米韦等神经氨酸酶抑制剂联合使用,成为当前抗流感药物研发的热点。本文综述了扎那米韦在治疗甲型流感方面的临床研究进展,重点关注了其对流感治疗作用,期望对流感临床药学应用发展提供新的用药治疗参考。Influenza A viruses are capable of causing a global pandemic due to their high mutability and transmissibility. Currently, anti-influenza virus drugs are the mainstay of clinical treatment for influenza, and these drugs exert their antiviral effects by blocking the entry, replication, and release of the virus. However, the ability of influenza viruses to mutate and evade the immune system has prompted researchers to continuously analyze new influenza A antiviral drugs. Zanamivir is a potent neuraminidase inhibitor that works by inhibiting the release of the virus from host cells, thereby limiting its spread through the body. As influenza viruses continue to mutate and increase drug resistance, single-drug regimens are no longer sufficient to meet the current influenza challenge. Therefore, the development of combinations with neuraminidase inhibitors, such as zanamivir, has become a hot topic in current anti-influenza drug development. This article reviews the clinical research progress of zanamivir in the treatment of influenza A, focusing on its therapeutic effect on influenza, and expects to provide new references for the development of influenza clinical pharmacy applications for drug therapy.
关键词: 扎那米韦 ；甲型流感 ；抗病毒药物 ；神经氨酸酶抑制剂
摘要： SGLT-2 (钠–葡萄糖协同转运蛋白2)抑制剂是一种新型降糖药,它作用于肾脏,能够降低肾脏重新吸收葡萄糖的能力,促使尿糖排泄量增加,最终达到降低血糖水平的效果。近年来,SGLT-2被发现不仅具有降糖的作用,还可以通过抑制葡萄糖代谢、抑制血管生成、影响免疫微环境等多个机制起到抗肿瘤的作用。目前,SGLT-2抑制剂在肺癌中的作用的研究仍处于初步阶段,这篇综述系统地阐述了SGLT-2抑制剂在肺癌中的研究进展,希望能为未来SGLT-2抑制剂在肺癌中的应用提供参考。SGLT-2 (sodium-glucose co-transporter protein-2) inhibitor is a new type of hypoglycemic drug, which acts on the kidneys and can reduce the kidney’s ability to reabsorb glucose, prompting an increase in urinary glucose excretion, and ultimately achieving the effect of lowering blood glucose levels. In recent years, SGLT-2 has been found to not only have a hypoglycemic effect, but also play an anti-tumor role by inhibiting glucose metabolism, inhibiting angiogenesis, affecting the immune microenvironment and other mechanisms. At present, the research on the role of SGLT-2 inhibitors in lung cancer is still in the preliminary stage, and this review systematically describes the research progress of SGLT-2 inhibitors in lung cancer, hoping to provide a reference for the future application of SGLT-2 inhibitors in lung cancer.
关键词: 糖尿病 ；肺癌 ；钠–葡萄糖协同转运蛋白2抑制剂
摘要： A lack of knowledge about genetic variation in minority populations throughout the world limits the potential uptake of genomic-based precision medicine in these often-underserved people.Extrapolation of pharmacogenetic results derived from more extensively studied populations to minority groups carries risk,as founder effects,genetic drift and unique selective pressures can result in the appearance of novel,functionally significant variants and the disappearance of ones common to a larger population.The NIH-funded Northwest-Alaska Pharmacogenetic Research Network was formed in 2010with the goal of addressing the pharmacogenetic knowledge deficit in Alaska native(AN)and American Indian(AI)populations.A collaboration of investigators at the University of Washington,University of Montana,University of Alaska-Fairbanks,Southcentral Foundation and Group Health Cooperative of Washington was formed to investigate genetic variation in key pharmacogenes and the resulting effect on drug disposition and response,with a focus on anticoagulation,antiplatelet and anticancer therapies.With regard to anticoagulation therapy,we sequenced and genotyped variation in the VKORC1,GGCX,CYP4F2,CYP4F11 and CYP2C9 genes in AN populations living in the interior and western Alaska.While no new variants in the VKORC1,GGCX,and CYP4F genes at frequencies≥1%were discovered,the reduced function-1639 variant in the VKORC1 gene associated with a lower warfarin dose requirement was found at a relatively high frequency in the western AN population(78%),similar to that seen in some Asian populations(92%),but not so high in the interior AN population(54%).The loss-of function CYP4F2*3 variant associated with a higher warfarin dose requirement was found at a frequency of 51%and 31%in the western and interior AN populations respectively,both higher than that found in most other world population(8%-29%).Interestingly,in the western AN population,the reduced function CYP4F2*3 allele was associated with both short-term(plasma vitamin K concentration)and long-term(plasma PIVKA-Ⅱconcentration)measures of vitamin K status,which can affect anti-coagulation control in warfarin-treatedpatients because of its essential role in the synthesis ofⅡ-carboxylated clotting factors(eg,FactorⅡ).CYP4F2catabolizes vitamin K to inactive metabolites.Individuals carrying the CYP4F2*3 allele were less likely to exhibit vitamin K insufficiency than those homozygous for the reference CYP4F2*1 allele.Moreover,the odds of longterm vitamin K insufficiency was lower in individuals reporting regular consumption of vitamin K rich foods than those who reported no consumption of those foods,and this risk factor was independent of CYP4F2*3 status.Inheritance of the CYP4F2*3 allele may enhance the hepatic vitamin K reserve and reduce the risk of major,unexpected bleeding events in individuals receiving longterm warfarin therapy,as we reported in a non-native population receiving care from Group Health Cooperative.With respect to warfarin metabolism,we identified two novel coding variants(M1L and N218I)in the CYP2C9 gene at frequencies of 6.3%and 3.8%in the western AN population and 1.4%and 5.4%in the interior AN population.In vitro studies indicate that the M1L variant will confer a complete loss of CYP2C9 function as a consequence of loss of the translation start codon.Interestingly,the common CYP2C9*2 and*3 variants associated with reduced CYP2C9 function and lower warfarin dose requirement were found at lower frequencies in both AN populations than that seen in Caucasians.Thus,genotyping for only previously known CYP2C9variants in an population would lead to significant misclassification and inappropriate genotype-guided dose recommendations.In the case of antiplatelet therapy,we examined the relationship between putative dietary modulators of platelet activation(ω3 polyunsaturated fatty acids;ω3PUFAs)and basal platelet activationin the same western AN population,using a novel,nitrogen-isotope based biomarker of dietaryω3 PUFA consumption and membraneω3 PUFA levels(δ15N;8).A significant fraction of the AN population in western Alaska adheres to a′traditional′diet of marine foods rich inω3 PUFAs.In that population,the degree of platelet activation,as determined by measurement of plasma s P-selectin concentration,correlated strongly and inversely withω3 PUFA consumption.This finding is consistent with older reports of nutritionally-based blood diathesis in other circumpolar populations.Thus,diet,or more specificallyω3 PUFA consumption,may modify the efficacy and safety of antiplatelet therapies.
关键词: PUFAs ；CYP
摘要： 阿芬太尼是一种作用于μ受体的新型芬太尼衍生物,为短效强阿片类镇痛药。由于其起效快、作用时间短、无明显药物蓄积,对呼吸和循环的抑制小,不良反应少,安全系数大等特点,目前被广泛应用于无痛胃肠镜检查中。本文结合国内外文献和阿芬太尼的临床药理特性、临床应用优势,给药方案,常用药物组合等方面的研究进展进行综述,旨在优化无痛胃肠镜检查中的麻醉用药方案,为阿芬太尼在临床上的使用提供理论依据。Alfentanil is a new type of fentanyl derivative acting on the μ receptor and is a short-acting and potent opioid analgesic. Due to its characteristics such as rapid onset, short duration of action, no obvious drug accumulation, little inhibition of respiration and circulation, few adverse reactions, and a large safety factor, it is currently widely used in painless gastrointestinal endoscopy. This article reviews the research progress in aspects such as the clinical pharmacological properties, clinical application advantages, administration regimens, and commonly used drug combinations of alfentanil, combined with domestic and foreign literature. It aims to optimize the anesthesia drug regimens for painless gastrointestinal endoscopy and provide a theoretical basis for the clinical use of alfentanil.
关键词: 阿芬太尼 ；无痛胃肠镜 ；药理学 ；靶控输注 ；复合麻醉
摘要： 综述阿司匹林和氯吡格雷在缺血性脑卒中急性期的应用研究进展。抗血小板治疗可以有效地降低缺血性脑卒中的复发率,阿司匹林和氯吡格雷作为抗血小板治疗的一线用药,目前相关研究及指南未明确阿司匹林和氯吡格雷在缺血性脑卒中急性期应用策略。
关键词: 缺血性脑卒中 ；阿司匹林 ；氯吡格雷 ；抗血小板治疗 ；综述
被引量
27
摘要： 随着炎症性肠病(IBD)治疗药物的不断更新,其治疗药物由传统氨基水杨酸、糖皮质激素和免疫抑制剂拓展至靶向生物制剂及小分子合成药物。但其出现的各种不良并发症以及药物失应答与安全性等问题不可避免,而作为参与淋巴细胞归巢过程中的整合素、黏附分子、部分趋化因子及其他分子,可能是未来靶向治疗IBD甚至自身免疫性疾病的重要方向。本文通过综述靶向参与淋巴细胞归巢的整合素、黏附分子和趋化因子与其他分子,简述了其在控制IBD疾病中的研究进展,为开发新型生物制剂治疗IBD提供更广阔的临床前景。With the continuous development of inflammatory bowel disease (IBD) treatment drugs, its therapeutic drugs have expanded from traditional aminosalicylic acid, glucocorticoids and immunosuppressants to targeted biologics and small molecule synthetic drugs. However, various adverse complications and drug failure and safety problems are inevitable. Integrins, adhesion molecules, partial chemokines and other molecules involved in the homing process of lymphocytes may be an important direction for targeted therapy of IBD and even autoimmune diseases in the future. This article reviews the integrins, adhesion molecules, chemokines and other molecules involved in lymphocyte homing, and briefly reviews their research progress in the control of IBD diseases, providing a broader clinical prospect for the development of new biologics for the treatment of IBD.
关键词: 炎症性肠病 ；整合素 ；黏附分子 ；趋化因子及其他分子 ；研究进展
摘要： 氯吡格雷作为最常用的一线抗血小板药,被广泛应用于心脑血管性疾病的二级预防治疗中。但在临床中,有部分患者存在氯吡格雷反应不佳,抗血小板作用不足现象,即氯吡格雷抵抗,导致缺血事件再发。目前多个研究显示,造成氯吡格雷抵抗的主要因素为参与氯吡格雷代谢的酶的基因多态性所致,而其中以CYP2C19基因为主。不同的等位基因可影响氯吡格雷活性代谢物的生成,从而影响其对血小板聚集的抑制作用。而基于CYP2C19基因检测进行氯吡格雷处方,指导个体化抗血小板治疗可有效减少患者主要不良心血管事件的发生,但如何进行个体化干预,目前尚无统一方案。本文就氯吡格雷抵抗与基因多态性的关系,及氯吡格雷抵抗治疗策略的研究进展做一综述,旨在帮助临床医生理解基因检测结果,及如何根据结果进一步优化药物治疗方案。
关键词: 氯吡格雷 ；氯吡格雷抵抗 ；基因多态性 ；抗血小板治疗
被引量
1
摘要： 缺血性脑卒中是危害人类健康的主要疾病之一。近年研究发现,多不饱和脂肪酸(PUFA)及其经细胞色素P450 (cytochrome P450,CYP)途径代谢的产物参与缺血性脑卒中的生理病理过程。血浆中ω-3多不饱和脂肪酸(ω-3 PUFA)、20-羟基二十碳四烯酸(20-HETE)和环氧二十碳三烯酸(EETs)浓度水平可反映疾病的预后,对CYP450途径代谢酶进行诱导或抑制可改善神经功能。此外,CYP2C19基因型与氯吡格雷抗血小板治疗效果及复发性缺血性脑卒中有关,因而鉴定基因型和选择合理治疗方案尤为重要。本文就缺血性脑卒中与CYP450代谢途径相关研究进展进行综述。
关键词: 缺血性脑卒中 ；细胞色素P450 ；20-羟基二十碳四烯酸 ；环氧二十碳三烯酸 ；ω-3多不饱和脂肪酸 ；氯吡格雷
被引量
2
摘要： 氯吡格雷是缺血性脑血管病抗血小板治疗的主要药物之一。氯吡格雷抵抗是缺血性脑血管病患者在应用氯吡格雷治疗期间缺血性脑血管事件复发的重要原因,及时发现并纠正氯吡格雷抵抗,对改善缺血性脑血管病患者的预后至关重要。文中对缺血性脑血管病患者氯吡格雷抵抗的定义、影响因素、诊断标准及防治策略的研究进展进行综述。
关键词: 氯吡格雷 ；药物抵抗 ；脑缺血 ；短暂性脑缺血发作 ；治疗
被引量
14
摘要： 抗血小板药物氯吡格雷是二磷酸腺苷(adenosine diphosphate,ADP)受体拮抗剂,是急性脑梗死或短暂性脑缺血发作(transient ischemic attack,TIA)的一级和二级预防的主要药物[1],但接受抗血小板药物治疗的患者中有很高比例会反复发生脑血管事件[2-3],称为血小板高反应性(high on-treatment platelet reactivity,HTPR),既往称之为氯吡格雷抵抗(clopidogrel resistance,CR)。发生率各家报道不同,占到16%~50%[4]。表明抗血小板药物抑制作用存在缺陷,可能导致不良临床血管事件,今就氯吡格雷治疗后HTPR影响因素的研究进展进行综述。
关键词: 抗血小板药物 ；急性脑梗死 ；血小板高反应性 ；氯吡格雷抵抗 ；脑血管事件 ；二级预防 ；二磷酸腺苷 ；受体拮抗剂
被引量
9
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