欧洲药物战略（2020）及其对中国医药领域的启示

在当前国际制药技术出现重大创新和变革、药品研发技术信息化和数字化程度不断发展，以及新型冠状病毒肺炎（COVID-19）疫情大流行的背景下，欧盟委员会为满足未竟临床需求、激励行业创新、增强监管系统应变能力、巩固欧盟药品监管体系国际地位，于2020年底发布了《欧洲药物战略》（Pharmaceutical Strategy for Europe，PSE）。PSE被视为欧洲未来5年卫生政策的“基石”，对欧洲制药领域发展和管理具有重要指导意义。通过对PSE制定背景及发展战略目标、具体举措等内容进行梳理分析，并结合中国COVID-19疫情防控与行业发展、药品科学监管与鼓励创新等实际工作提出政策建议。     

A Well-Balanced Positivity-Preserving Quasi-Lagrange Moving Mesh DG Method for the Shallow Water Equations

A high-order, well-balanced, positivity-preserving quasi-Lagrange moving mesh DG method is presented for the shallow water equations with non-flat bottom topography. The well-balance property is crucial to the ability of a scheme to simulate perturbation waves over the lake-at-rest steady state such as waves on a lake or tsunami waves in the deep ocean. The method combines a quasi-Lagrange moving mesh DG method, a hydrostatic reconstruction technique, and a change of unknown variables. The strategies in the use of slope limiting, positivity-preservation limiting, and change of variables to ensure the well-balance and positivity-preserving properties are discussed. Compared to rezoning-type methods, the current method treats mesh movement continuously in time and has the advantages that it does not need to interpolate flow variables from the old mesh to the new one and places no constraint for the choice of a update scheme for the bottom topography on the new mesh. A selection of one- and two-dimensional examples are presented to demonstrate the well-balance property, positivity preservation, and high-order accuracy of the method and its ability to adapt the mesh according to features in the flow and bottom topography.     

Synthesis of 13C-labeled parabens from isotopically enriched phenols using the Houben–Hoesch reaction

Parabens are antimicrobial additives found in a wide array of consumer products. However, the halogenated compounds formed from parabens during wastewater disinfection are a potential environmental concern. In order to identify these transformation products and investigate their mechanism of formation, a synthetic route to ethyl parabens labeled with the stable isotope carbon-13 at specific positions within the benzene ring was developed. This efficient two-step procedure starts from commercially available ¹³C-labeled phenols and involves (1) initial acylation of the phenol via a Houben–Hoesch reaction with trichloroacetonitrile followed by (2) a modified haloform reaction of the resulting trichloromethyl ketone to afford the corresponding ¹³C-labeled ethyl parabens in 65%–80% overall yield. The scope of the modified haloform reaction was also investigated, allowing for the synthesis of other parabens derived from primary or secondary alcohols, including ¹³C- and deuterium-labeled esters. In addition, 4-hydroxybenzoic acid can be formed directly from the common trichloromethyl ketone intermediate upon treatment with lithium hydroxide. This protocol complements existing methods for preparing ¹³C-labeled paraben derivatives and offers the specific advantages of exhibiting complete regioselectivity in the Houben–Hoesch reaction (to form the para-disubstituted product) and avoiding the need for protecting groups in the modified haloform reaction that forms the paraben esters.     

《邵氏医案》从血辨治痛经浅析

[目的]分析总结浙江近代著名临床医家邵兰荪治疗痛经的经验,以期为临床治疗提供借鉴。[方法]通过研读裘吉生编《邵氏医案》,筛选出其中治疗痛经的医案十余则,并结合邵氏在妇科方面的学术思想,进一步分析其辨证立法遣方特色,从而总结邵氏治疗痛经的临证经验。[结果]邵氏治疗痛经多从血辨治,且分虚实两端,其中属虚者血虚内热用益母胜金丹养血清热、活血止痛,血虚肝风治以养血柔肝、息风止痛;属实者水结血瘀用五苓散利水散瘀、行气止痛,气阻血滞治从行气活血、调经止痛。[结论]在治疗妇人痛经方面,邵氏辨治遣方确有独特经验,这些经验可为中医药治疗此类疾病拓宽诊治思路,有助于提高临床疗效。     

深圳市龙岗区饮用水中常规指标的健康风险评价

目的：评估深圳市龙岗区饮用水对人体的健康风险。方法：对深圳市龙岗区饮用水中砷（As）、三氯甲烷、四氯化碳、镉（Cd）、六价铬（Cr⁶⁺）、铁（Fe）、锰（Mn）、铜（Cu）、锌（Zn）、铅（Pb）、硒（Se）、汞（Hg）、氨氮、氟化物、硝酸盐氮共15种常规指标进行检测，按照美国国家环保署（US EPA）推荐的方法，建立水环境污染健康风险评价模型，对常规指标经饮水途径引起的健康风险进行评价。结果：饮用水中致癌物按健康风险大小排列为Cr⁶⁺ > As > Cd > 三氯甲烷 > 四氯化碳；非致癌物质按健康风险大小排列为氟化物 > 硝酸盐氮 > Hg > Cu > Pb > Se > Zn > 氨氮 > Mn > Fe。深圳市龙岗区饮用水个人健康危害总风险度为4.113×10^-5，范围3.906×10^-5~9.457×10^-5。结论：深圳市龙岗区饮用水中常规指标经饮水途径引起的健康风险接近国际辐射防护委员会（ICRP）推荐的最大可接受水平（5×10^-5），小于US EPA推荐的最大可接受水平（1×10^-4）。