Structure-based design of novel heterocyclesubstituted ATDP analogs as non-nucleoside reverse transcriptase inhibitors with improved selectivity and solubility

Following on our recently developed biphenyl-ATDP non-nucleoside reverse transcriptase inhibitor ZLM-66(SI=2019.80,S=1.9μg/mL),a series of novel heterocycle-substituted ATDP derivatives with significantly improved selectivity and solubility were identified by replacement of the biphenyl moiety of ZLM-66 with heterocyclic group with lower lipophilicity.Evidently,the representative analog 7w in this series exhibited dramatically enhanced selectivity and solubility(SI=12,497.73,S=4472μg/mL)in comparison with ZLM-66(SI=2019.80,S=1.9μg/mL).This new NNRTI conferred low nanomolar inhibition of wild-type HIV-1 strain and tested mutant strains(K103N,L1001,Y181C,E138K,and K103N+Y181C).The analog also demonstrated favorable safety and pharmacokinetic profiles,as evidenced by its insensitivity to CYP and hERG,lack of mortality and pathological damage,and good oral bioavailability in rats(F=27.1%).Further development of 7w for HIV therapy will be facilitated by this valuable information.

当前我国农业立体污染防治研究的若干重要问题

丰富了农业立体污染新观念的内涵,分析了我国农业立 体污染的严峻现状、研究与防治实践中存在的问题,重点阐述 了我国农业立体污染防治中监测信息网络建设、相关基础理 论与科学体系构建、关键技术集成与攻关、政策法规等保障体 系建设等重要问题。

中心摆药室使用全自动药品分包机的体会与评价

目的:评价我院引进全自动药品分包机的使用体会。方法:对这一年使用全自动药品分包机的优缺点进行总结与分析。结果:全自动药品分包机具有提高摆药速度和准确度、减少药品污染、增加服药依从性等优点,同时也存在机器、耗材成本等问题。结论:全自动药品分包机提高了药学服务水平,是医院自动化进展的趋势,值得临床推广和使用。

根因分析法用于自动包药机管理效果分析

目的提升自动包药机的工作性能和药品管理水平。方法采用根因分析(RCA)法分析住院药房自动包药机运行中存在问题发生的近端原因与根本原因,并制订相应改进措施。比较7个病区RCA法实施前(2023年3月至5月)和实施后(2023年6月至8月)自动包药机的日均分包数量、日均调剂时间、日均溢袋数量、月均分包差错、包药机内药品月均滞销品种数及其占比、月均患者满意度。结果RCA法实施后,自动包药机的日均溢袋数量、月均分包差错、药品月均滞销品种数、月均滞销品种数占比分别为0包、(3.48±0.94)例、(6.67±1.16)种、(1.14±0.20)%,分别显著低于实施前的(5.20±1.82)包、(7.86±2.29)例、(16.00±1.00)种、(2.73±0.17)%(P<0.05)。结论RCA法用于住院药房自动包药机管理,可提升药品分包的质量与效率,提升住院药房的管理水平。