国家药品标准物质保障供应综合数据平台建设

目的：进一步提高国家药品标准物质供应保障的能力和水平,更好支撑药品监管需求和服务行业发展。方法：将信息化管理和分析方法与现有的标准物质管理技术要求相结合,研究建立数字化、可视化的数据共享系统。结果：建成的国家药品标准物质保障供应综合数据平台,可显示各品种的研制生产阶段和效率。结论：该平台试运行一年来已成为指导研制、生产和管理的有力抓手,为对接国际标准ISO 17034奠定了重要基础。     

FMEA在降低自动口服摆药机调剂差错风险中的应用

目的：探讨失效模式和影响分析（failure mode and effect analysis,FMEA）在降低自动口服摆药机调剂差错风险中的应用。方法：运用FMEA识别自动口服摆药机调剂过程中的失效模式,分析其出现的原因,制定降低调剂差错的措施。结果：实施风险控制措施后,影响自动口服摆药机调剂差错风险失效模式的风险优先指数（risk priority number,RPN）值由119分降到55分,差异具有统计学意义（P<0.05）。结论：FMEA应用于自动口服摆药机调剂差错的风险管理,可有效降低调剂差错,提高药学服务质量。     

CYP2D6联合CYP1A2基因多态性对老年晚期癌症伴发 抑郁状态患者奥氮平个体化用药的指导研究

目的：研究老年晚期癌症伴发抑郁状态患者细胞色素酶P450（Cytochrome P450,CYP）2D6联合CYP1A2基因多态性指导奥氮平（olanzapine,OLA）个体化用药。方法：选取2016年9月~2018年1月入院治疗的老年晚期癌症伴发抑郁状态患者80例,利用SPSS 23.0软件随机分为对照组20例和试验组60例,第1周对照组根据经验给予奥氮平初始剂量5 mg·d-1,试验组根据CYP2D6联合CYP1A2基因型给予不同初始剂量奥氮平（联合快代谢型为7.5 mg·d-1,中等代谢型为5 mg·d-1）。第2、3、4周根据奥氮平血药浓度、病情、不良反应调整剂量。给药后第1、4周末,比较两组血药浓度达标情况及疗效。结果：第1周末,试验组血药浓度、达到靶血药浓度范围患者比例、标准化血药浓度、HAMD-24减分率显著高于对照组[（14.13±3.95） vs. （9.59±3.83） ng·L-1,86.7% vs. 60.0%,（38.90±15.51） vs.（30.93±13.55） ng·mL-1·mg-1·kg-1,（28.17±6.52）% vs.（23.27±5.45）%,P<0.05],试验组4周调整剂量患者比例显著低于对照组（20.0% vs. 50.0%,P<0.05）。第1、4周末,试验组快代谢型与中等代谢型患者上述指标均无显著差异（P>0.05）。第1周末,试验组快代谢型患者血药浓度、达到靶血药浓度范围患者比例、标准化血药浓度、HAMD-24减分率显著高于对照组快代谢型[（15.13±3.61） ng·L-1 vs. （6.27±2.62） ng·L-1,86.9% vs. 14.3%,（32.53±11.45） ng·mL-1·mg-1·kg-1 vs. （19.27±8.00） ng·mL-1·mg-1·kg-1,（28.49±5.96）% vs. （21.01±5.44）%,P<0.05],试验组快代谢型4周调整剂量患者比例显著低于对照组快代谢型（17.4% vs. 100.0%,P<0.05）。结论：根据CYP2D6联合CYP1A2基因代谢型指导老年晚期癌症伴发抑郁状态患者服用奥氮平的初始剂量,能够更加有效地使各代谢型患者在治疗早期尽快达到有效奥氮平血药浓度。     

Palmitate enhanced the cytotoxicity of ZnO nanomaterials possibly by promoting endoplasmic reticulum stress

We recently synthesized ZnO nanomaterials (denoted as ZnO nanorods [NRs] and Mini‐NRs) and suggested that their cytotoxicity could be related with the activation of endoplasmic reticulum (ER) stress apoptosis. However, in a complex biological microenvironment, the ER stress‐apoptosis pathway could also be modulated by biological molecules, such as free fatty acids, leading to unpredicted biological effects. In this study, we investigated the combined toxicity of ZnO NRs/Mini‐NRs and palmitate (PA) to THP‐1 macrophages. PA influenced the zeta potential and solubility of ZnO NRs and ZnO Mini‐NRs in water, which indicated a change of colloidal stability. Exposure to ZnO NRs and Mini‐NRs dose‐dependent decreased cellular viability and release of soluble monocyte chemotactic protein 1 (sMCP‐1), and these effects were significantly promoted with the presence of PA. However, ZnO NR‐ and Mini‐NR‐induced intracellular Zn ions or reactive oxygen species were not significantly affected by PA. ZnO NRs and ZnO Mini‐NRs significantly promoted the expression of ER stress genes HSPA5, DDIT3, XBP‐1s and apoptotic gene CASP3, whereas PA also modestly promoted the expression of HSPA5, DDIT3 and CASP3. Interestingly, the ER stress inducer thapsigargin showed a similar effect as PA to promote the cytotoxicity of ZnO NRs and ZnO Mini‐NRs. It is suggested that PA might promote the cytotoxicity of ZnO NRs and ZnO Mini‐NRs possibly by promoting ER stress.     

Anticancer properties of novel pyrazole‐containing biguanide derivatives with activating the adenosine monophosphate‐activated protein kinase signaling pathway

Biguanides, including metformin and phenformin, have emerged as promising anticancer agents. However, the high dose needed for their efficient anticancer properties restricts their clinical application. In an attempt to obtain higher active compounds than these parent compounds, pyrazole‐containing biguanide derivatives were synthesized and screened for in vitro cytotoxicity against human cancer cell lines. Clonogenic assays and scratch wound healing assays demonstrated that these new derivatives profoundly inhibit cell proliferation and migration. Compounds 10b and 10d exhibited strong potency with low IC₅₀ values in the range of 6.9‐28.3 μM, far superior to phenformin and metformin. Moreover, 20 μM 10b and 10d resulted in 72.3‐88.2% (p < 0.001) inhibition of colony formation and 29.3‐60.7% (p < 0.05) inhibition of cell migration. Mechanistically, 10b and 10d activated adenosine monophosphate‐activated protein kinase, leading to inactivation of the mammalian target of rapamycin (mTOR) signaling pathway with the regulation of 4EBP1 and p70S6K. These results suggest the value of these novel biguanide derivatives as candidates with therapeutic potential for the treatment of bladder and ovarian cancer.