Objective:This study aims to summarize the achievements of the research wards in a large grade A tertiary hospital in Beijing, discuss the important role of pharmacists, and provide a reference for improving the functions and responsibilities of pharmacists in the research ward construction.Methods:Combining the practice of research ward construction in a grade A tertiary hospital in Beijing, the important role of pharmacists in the construction and operation of research wards were analyzed in system construction, information construction, analysis laboratory construction, and project management.Results:The participation of pharmacists with professional pharmaceutical knowledge and familiarity with the relevant policies and regulations of clinical research can greatly improve the quality and efficiency of research ward construction and operation.Conclusions:Pharmacists' participation in the construction of research wards is beneficial to improving clinical research ability and quality, and is of great significance to the development of China′s pharmaceutical health industry.

Objective:This study aims to summarize the construction and operation results of a clinical research support platform in a large grade A tertiary hospital in Beijing, and to explore the top-level design, functional positioning, and operation management based on research wards, thereby providing a reference for improving the clinical research support system in China.Methods:Guided by the needs of clinical research, the clinical research support platform consisted of seven core functional units, including the clinical trial platform, medical ethical review platform, medical experiment and clinical testing platform, clinical research big data platform, clinical research methodology platform, scientific and technological achievements transformation platform, and biobank.Results:The clinical research support platform with perfect functions, scientific management, and efficient operation can provide strong technical support for efficient operation of research wards, high-quality development of clinical trials, and rapid transformation of innovative results.Conclusions:A high-level clinical research support platform can effectively integrate medical resources, promote resource sharing and cooperation, promote the deep integration of industry, academia, research, and medicine, and enhance the collaboration and scientific level of clinical research.

GB223 is a novel, fully-humanized monoclonal antibody against the receptor activator of nuclear factor-kappa B ligand (RANKL). In this phase I study, the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of GB223 were investigated. This was a randomized, double-blinded, placebo-controlled, single-dose escalation study conducted in 44 healthy Chinese adults. Participants were randomly assigned to receive a single subcutaneous injection dose of 7, 21, 63, 119, or 140 mg of GB223 (n = 34) or placebo (n = 10) and were followed up for 140–252 days. The results of noncompartmental analysis showed that GB223 was slowly absorbed after dosing, with a time to reach maximum concentration (Tmax) ranging from 5 to 11 days. Serum GB223 concentrations decreased slowly, with a long half-life ranging from 7.91 to 19.60 days. A two-compartment Michaelis–Menten model was found to best describe the pharmacokinetics of GB223, and the absorption rate of GB223 differed between males (0.0146 h-1) and females (0.0081 h-1). Serum C-terminal telopeptide of type I collagen decreased significantly postdose, and the inhibition lasted 42–168 days. No deaths or drug-related serious adverse events occurred. The most frequent adverse events were blood parathyroid hormone increased (94.1

Filgotinib是治疗对一种或多种改善病情抗风湿药(DMARDs)反应不佳或不耐受的中重度活动性类风湿关节炎(RA)成人患者的JAK1抑制剂,于2020年9月24日由欧洲药品管理局(EMA)和日本厚生劳动省(MHLW)批准上市.大量临床研究表明,Filgotinib对RA的疗效明确、安全性和耐受性良好.本文对Filgotinib的药理作用及作用机制、临床药代动力学、临床疗效、安全性、用法用量及药物相互作用等方面进行综述,同时介绍了临床研究最新进展,旨在为RA的创新临床治疗提供参考.

目的 考察常春藤皂苷元对人肝微粒体中的5种细胞色素P450(CYP450)酶的抑制作用.方法 采用Cocktail探针药物法,在肝微粒体中加入常春藤皂苷元与混合探针底物[包含非那西丁(CYP1 A2探针底物)、双氯芬酸钠(CYP2C9探针底物)、苯乙妥英(CYP2C19探针底物)、右美沙芬(CYP2D6探针底物)和咪达唑仑(CYP3A4探针底物)]共同孵育60 min.采用超高效液相色谱-质谱联用法(UPLC-MS/MS),以甲苯磺丁酰胺为内标,定量检测底物的代谢物含量,并计算常春藤皂苷元和特异性抑制药对人肝微粒体中CYP1 A2、CYP2D6、CYP2C19、CYP2C9和CYP3A4的半数抑制浓度(IC50).结果 常春藤皂苷元对人肝微粒体中CYP1A2、CYP2D6与CYP3A4的IC50值均大于50μmol·L-1,对CYP2C9及CYP2C19的IC50值分别为4.94μmol·L-1和18.00μmol·L-1.结论 常春藤皂苷元对肝微粒体中CYP1A2、CYP2D6与CYP3A4无明显抑制作用,对CYP2C9和CYP2C19有一定的抑制作用.

Dostarlimab是一种抗程序性死亡受体1(anti-PD-1)阻断抗体,用于治疗DNA错配修复功能缺陷(dMMR)的晚期或复发性实体瘤成人患者,这些患者在先前治疗后病情进展,且没有令人满意的替代治疗方案.dMMR状态是一种可以预测肿瘤对免疫检查点抑制剂反应的有效生物标志物,其在子宫内膜癌、胃癌、结直肠癌等实体瘤中发病率较高.本文就Dostarlimab的药理作用及作用机制、药物代谢动力学、临床疗效和安全性评价等进行综述.

Risankizumab是一种治疗中重度斑块型银屑病成人患者的最新白细胞介素23(IL-23)抑制剂,2019年4月23日由美国食品药品管理局(FDA)批准上市.大量研究表明,Risankizumab的疗效优于此前治疗斑块型银屑病的主流药物肿瘤坏死因子α(TNF-α)抑制剂和IL-12/IL-23抑制剂等,其将成为斑块型银屑病治疗的未来趋势.为进一步加深临床工作者对Risankizumab的认识与理解,本文主要针对Risankizumab治疗斑块型银屑病的作用机制、药物代谢动力学、临床疗效和安全性等进行综述,同时与其他相关药物进行对比.

目的 探讨rhGLP-1(7-36)对糖尿病肾病(diabetic kidney disease,DKD)大鼠肾脏的保护机制.方法 DKD模型大鼠随机分成模型组、rhGLP-1(7-36)低剂量组(20μg·kg-1)、rhGLP-1(7-36)中剂量组(40 μg·kg-1)、rhGLP-1(7-36)高剂量组(80 μg-kg-1),另设正常组,皮下注射给药4周.全自动生化分析仪检测24h尿微量白蛋白、血肌酐及尿肌酐水平,计算肌酐清除率;进行腹腔糖耐量实验并计算药时曲线下面积(areaunderthecure,AUC);HE染色行肾组织病理形态学观察;Western blotting检测肾组织SIRT1蛋白水平.结果 与模型组相比,rhGLP-1(7-36)高剂量组大鼠肌酐清除率有明显改善(P＜0.05);24h尿微量白蛋白水平明显下降(P＜0.05);腹腔糖耐量AUC水平明显减小(P＜0.05);肾组织病理变化有不同程度改善;肾组织SIRT1蛋白水平明显上升(P＜0.05).结论 rhGLP-1(7-36)能有效改善DKD大鼠的肾脏功能,其机制可能与上调肾脏组织的SIRT1水平有关.

The sustained effect of myocardial hypertrophy can cause heart damage and dysfunction, resulting in heart failure or death. MicroRNAs, important regulators, are involved in the progress of cardiac hypertrophy. Recently, increasing studies show that microRNAs can promote or curb cardiac hypertrophy. In addition, microRNAs are considered potential biomarkers for cardiovascular diseases assessment. Therefore, this review focuses on the effect of microRNAs on cardiac hypertrophy.

双特异性抗体能够识别并结合两种不同抗原的抗体,与普通抗体药物相比具有灵敏度高、特异性强、以及能够同时阻断多条疾病通路的优势.迄今为止,全球共有3款双特异性抗体药物已上市,近100种双特异性抗体在研,展现出广阔的开发前景.双特异性抗体药物的免疫原性指其进入体内后会引起机体免疫反应产生抗药抗体,可能对药物的药代动力学、药效动力学性质产生影响.本文对卡妥索单抗(catumaxomab)、博纳吐单抗(blinatumomab)、艾美赛珠单抗(emicizumab)的免疫原性相关研究进展进行综述,以期为双特异性抗体的安全性、有效性以及临床合理应用提供参考.

腺苷三磷酸结合盒转运蛋白家族成员乳腺癌耐药蛋白(ABCG2)参与多种药物的吸收、分布和消除,是涉及药物肠道吸收或渗透最重要的外排转运蛋白之一,具有多功能外排泵的作用.ABCG2基因单核苷酸多态性与多种药物的药代动力学相关.本文就ABCG2基因单核苷酸多态性与药物药代动力学关系的最新研究进行综述.

Erdafitinib是一种口服成纤维细胞生长因子受体(FGFR)抑制剂,用于治疗局部晚期或转移性尿路上皮癌(mUC)的成人患者.该类患者具有FGFR3或FGFR2基因突变,曾接受过至少1种铂类化疗方案(包括新辅助或辅助铂类化疗方案)治疗的12个月内出现疾病进展.美国食品药品监督管理局(FDA)于2019年4月12日加速批准了erdafitinib上市,这是FDA批准的首个针对此适用证的靶向药物.本文就erdafitinib的作用机制、药代动力学、临床评价、安全性、用法用量以及药物相互作用作一概述,以期为临床用药提供参考.

表皮生长因子受体(EGFR)在许多恶性肿瘤中过度表达,针对EGFR的靶向药物可以有效、高选择性地抑制EGFR活性,从而有效治疗多种恶性肿瘤.EGFR靶向药物目前主要包括小分子表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs)、单克隆抗体(mAbs)以及抗体偶联药物(ADC)等.本文将就EGFR靶向药物的作用机制、药物分类和联合治疗做一综述.

微小RNA(miRNA)和长链非编码RNA (LncRNA)作为保守的非编码RNA,是肾细胞癌增殖、转移和靶向治疗的关键调控因子,与酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKI)治疗肾细胞癌的敏感性、耐药性及预后密切相关.本文归纳总结了miRNA及LncRNA作为生物标志物预测TKI治疗肾细胞癌的反应性及其与TKI耐药机制的关系.

目的:预测青皮挥发油防治阿尔茨海默病(AD)的主要活性成分和潜在作用靶点.方法:采用气质联用技术(GC-MS)分析青皮挥发油化学成分,并借助NIST 11.L数据库和人工数据解析进行成分的结构鉴定.借助中药系统药理学分析平台(TCMSP)、PharmMapper数据库等预测青皮挥发油活性成分及其对应靶点,借助GeneCards数据库、人类孟德尔遗传数据库等挖掘AD相关靶点;利用Venny 2.1.0软件映射以获取青皮挥发油防治AD的直接靶点;借助STRING数据库和Cytoscape 7.2.1软件挖掘核心节点,利用Venny2.1.0软件映射并去重后获取青皮挥发油防治AD的间接靶点;借助DAVID 6.7数据库对上述直接和间接靶点(即作用靶点)进行基因本体(GO)功能富集和KEGG通路富集分析;采用Cytoscape 7.2.1软件,以节点度值、介数中心度、紧密中心度为指标,对青皮挥发油“活性成分-作用靶点”网络进行拓扑学分析,挖掘关键成分和关键靶点.结果 与结论:GC-MS法共分离并鉴定出青皮挥发油化学成分40个,均为活性成分,包括右旋柠檬烯、γ-萜品烯等.共挖掘出活性成分对应靶点151个、AD相关靶点1 291个,其中直接靶点48个、间接靶点41个.上述89个作用靶点主要富集于细胞分数、轴突、胞浆等细胞组分,细胞内信号级联、对有机物的反应等生物过程,蛋白激酶活性、胺受体活性等分子功能,以及癌症通路、钙信号通路、神经营养素信号通路等信号通路(P＜0.05).共挖掘出α-萜品烯、β-elemen、百里酚、(-)-4-萜品醇等关键成分10个,雄激素受体(AR)、前列腺素G/H合酶2 (PTGS2)、丝裂原活化蛋白激酶14、毒蕈碱乙酰胆碱受体M1等关键靶点21个,表明青皮挥发油防治AD呈多成分、多靶点、多通路的作用特点.

目的 探讨中国健康绝经期妇女细胞色素P450酶2A6(CYC2A6)基因多态性及临床多因素对来曲唑药代动力学的影响.方法 纳入38例中国健康绝经期妇女,单次给予来曲唑片2.5 mg,采用HPLC-MS/MS法测定来曲唑血药浓度,计算药代动力学参数,比较不同基因型对Ka、Tmax、Cmax、Vd、CL、t1/2的影响.同时,结合临床多因素,全面考察基因多态性及临床多因素对来曲唑药代动力学的影响.结果 单因素方差分析表明,CYP2 A6*9不同基因型TT、TG之间的CL和t1/2差异均有统计学意义(P<0.05);多因素协方差分析表明,Vd与体重指数(BMI)呈正相关(P<0.05),与总胆红素(TBIL)呈负相关(P<0.05);CYP2A6*4和*9型突变显著降低CL(P<0.05),CL与BMI呈正相关(P<0.05),与谷草转氨酶(GOT)呈负相关(P<0.05);CYP2A6*9型突变显著延长t1/2(P<0.05).结论 CYP2 A6*4和*9基因多态性可影响来曲唑代谢,BMI及肝功能也对来曲唑的代谢显示出一定影响,建议使用来曲唑前充分考虑CYP2 A6基因多态性和患者个体特征,确保临床用药安全.

目的:分析健康受试者口服pazopanib片后体内药代动力学(PK)规律,初步探讨pazo-panib片PK个体差异的遗传学机制.方法:14例健康男性受试者分别在给药当天单次口服pazo-panib片(200 mg)后,采集基线至96 h血液样本,用LC-MS/MS法测定服药后各时间点血药浓度,用WinNonlin 6.3软件计算药代动力学相关参数,采用SNapShot法测定细胞色素P4503A4(CYP3A4)基因多态性.结果:Cmax变化范围(7361.65-26081.00)ng/mL,平均值 ± 标准差(15410.72±6366.21)ng/mL;tmax变化范围(1.50-4.00)h、平均值±标准差(2.50±0.83)h;AUC0-t变化范围(228013.55-775231.63)ng·mL-1·h,平均值±标准差(516279.90±175688.41)ng·mL-1·h.个体间Cmax、AUC相差达3倍以上,tmax可相差2倍以上;14例受试者CYP3A4(RS35599367)位点皆为野生型.结论:pazopanib片在中国健康男性志愿者中个体差异较大,未观察到CYP3A4(rs35599367)位点单核苷酸多态性,pazopanib个体间PK差异可能与其他药物代谢相关基因多态性有关.

目的 评价3种单硝酸异山梨酯缓释片在中国健康成年人体内的药代动力学行为与相对生物利用度.方法 纳入健康受试者12例,采用单中心、随机、开放、单次给药、三周期、三序列、交叉试验研究设计方法,受试者随机交叉单次口服受试制剂(T1、T2)和参比制剂(R)40 mg,用LC-MS/MS法测定单硝酸异山梨酯血药浓度,用WinNonlin 6.3软件计算药代动力学相关参数.结果 受试者服用受试制剂(T1、T2)和参比制剂(R)后,血浆中单硝酸异山梨酯缓释片受试制剂(T1、T2)和参比制剂(R)Cmax分别为(548.00±66.53),(511.08±80.80),(572.92±81.70)ng·mL-1;tmax分别为(5.75±1.73),(4.42±1.04),(4.21±0.69)h;AUC0-t分别为(7810.24±1084.02),(7535.29±1061.05),(7787.37±1263.02) ng·mL-1·h;AUC0-∞分别为(7878.44 ± 1078.90),(7603.18 ±1053.82),(7863.97 ±1274.41)ng· mL-1·h;平均相对生物利用度为100.69％和97.19％.结论 三种单硝酸异山梨酯缓释片具有生物等效性.

Aim: The long-term efficacy of cytokine-induced killer cellular therapy for hepatocellular carcinoma patients after curative treatments remains controversial. Methods: A meta-analysis was conducted, and the outcomes were the recurrence rate and overall survival. Results: Eight randomized clinical trials with 1038 participants were included. Compared with the control group, cytokine-induced killer cellular therapy group could reduce 1-year, 3-year recurrence rates, as well as improve 1-5 years overall survival for hepatocellular carcinoma patients (p < 0.05). However, it failed to affect the 5-year recurrence rate and 6-year overall survival (p > 0.05). Conclusion: Cytokine-induced killer cellular adjuvant therapy exerted a favorable role in improving early and long-term efficacy for hepatocellular carcinoma patients.