经典名方厚朴麻黄汤物质基准质量标准及制剂提取工艺研究

目的 建立厚朴麻黄汤物质基准质量标准,并优化其制剂提取工艺。方法 制备15批厚朴麻黄汤物质基准对应实物并检测出膏率。采用高效液相色谱法检测指标性成分（厚朴酚、和厚朴酚、盐酸麻黄碱及盐酸伪麻黄碱）含量与特征图谱,分析指标性成分从饮片到对应实物的转移率,评价特征图谱的相似度。以出膏率、指标性成分转移率为指标,采用L₉（3⁴）正交试验优化厚朴麻黄汤的制剂提取工艺（液料比、提取时间、提取次数）。结果 15批对应实物的出膏率为11.10%~13.13%,指标性成分质量分数及饮片-对应实物转移率分别为厚朴酚0.034%~0.051%、1.474%~2.801%,和厚朴酚0.030%~0.059%、2.154%~4.241%,盐酸麻黄碱0.309%~0.377%、23.278%~37.774%,盐酸伪麻黄碱0.138%~0.233%、27.417%~47.658%。各批次特征图谱与对照图谱间的相似度均大于0.9。综合考虑出膏率、成分转移率及生产实际,确定最优工艺为提取3次,分别加8、6、6倍量水,分别提取1.0、1.0、0.5 h。结论 结合出膏率、指标性成分含量及特征图谱对厚朴麻黄汤的物质基准质量属性进行全面分析,并优化其制剂提取工艺,可为厚朴麻黄汤质量标准的建立及后续开发提供参考。     

Effects of short-term in vivo exposure to polybrominated diphenyl ethers on thyroid hormones and hepatic enzyme activities in weanling rats.

Polybrominated diphenyl ethers (PBDEs), used as flame retardants, are ubiquitous environmental contaminants. PBDEs act as endocrine disruptors via alterations in thyroid hormone homeostasis. We examined thyroid hormone concentrations and hepatic enzyme activity in weanling rats exposed to three commercial PBDE mixtures: DE-71, DE-79, and DE-83R. Female Long-Evans rats, 28 days old, were orally administered various doses of DE-71, DE-79, or DE-83R for 4 days. Serum and liver samples were collected 24 h after the last dose and analyzed for serum total thyroxine (T(4)), triiodothyronine (T(3)), thyroid-stimulating hormone (TSH), hepatic microsomal ethoxy- and pentoxy-resorufin-O-deethylase (EROD and PROD), and uridinediphosphate-glucuronosyltransferase (UDPGT) activities. The PBDE-treated groups did not exhibit significant changes in body weight; however, increased liver weights, as well as 10- to 20-fold induction in EROD and 30- to 40-fold induction in PROD were found in the DE-71-- and DE-79--treated animals. DE-71 and DE-79 caused dose-dependent depletion of T(4), accompanied by up to 3- to 4-fold induction in UDPGT activities. Serum total T(4) was decreased a maximum of 80% for DE-71 and 70% for DE-79 in the highest dose, with benchmark doses (BMDs) of approximately 12.74 mg/kg/day for DE-71 and 9.25 mg/kg/day for DE-79. Dose-related effects in serum T(3) levels were less apparent, with maximal reductions of 25-30% at the highest dose for both DE-71 and DE-79. The two mixtures showed no effect on serum TSH levels. Benchmark dose analysis revealed that the two mixtures were comparable in altering thyroid hormone levels and hepatic enzyme activity. DE-83R was not effective in altering any of the measured parameters. The present study suggests that short-term exposure to some commercial PBDE mixtures interferes with the thyroid hormone system via upregulation of UDPGTS:     

加味柴胡疏肝散基准样品HPLC指纹图谱及关键质量属性量值传递规律研究

目的 建立加味柴胡疏肝散（Modified Chaihu Shugan Powder,MCSP）基准样品HPLC指纹图谱及多成分含量测定的方法,结合化学模式分析,探究关键质量属性的传递规律。方法 制备40批MCSP样品,利用HPLC法,以乙腈-0.2%磷酸水溶液为流动相,采用“中药色谱指纹图谱相似度评价软件（2012年版）”计算其相似度,结合化学计量法分析多产地多批次MCSP基准样品,结合指标性成分含量以及转移率,进行量值传递分析及整体质量研究。结果 建立的40批MCSP基准样品相似度大于0.90,指纹图谱相似度良好,29个共有峰中指认出其中13个色谱峰,所建立的多成分含量测定方法稳定可靠。芍药内酯苷、芍药苷、阿魏酸、芸香柚皮苷、柚皮苷、橙皮苷、橙皮素、新橙皮苷、去氢木香内酯、柴胡皂苷A的平均转移率分别为29.96%、22.08%、32.98%、22.42%、33.26%、15.50%、34.23%、56.94%、8.66%、8.69%。结论 采用指纹图谱结合多指标成分含量测定及转移率等评价指标对MCSP基准样品进行了量值传递综合考察,初步构建MCSP全过程质量控制体系,为制剂开发及MCSP的进一步研究提供参考。     

基于生物活性与效应基准的中药质量 评价技术发展现状与展望

中药质量的评控问题是制约中药现代化发展的瓶颈,因此有必要在现有检测方法的基础上结合生物评价,继而更为全面地保证中药质量。生物评价是完善中药质量标准、保证临床功效和安全性评价的重要方法,已成为中药质量标准化发展趋势之一。在此处主要论述了近年来基于生物活性与效应基准的中药质量评价技术和已取得的部分研究进展,同时对目前中药质量生物评价研究与应用中存在的主要问题进行探讨,进一步对其未来应用做出展望,从而更好的对中药质量进行控制。     

SLS人体单次斑贴试验阳性对照物基准模型的建立

目的:建立十二烷基磺酸钠(SLS)人体单次斑贴试验阳性基准模型。方法:60名健康受试者使用0.01%、0.05%、0.10%、0.50%和1.00%SLS进行第一阶段皮肤单次斑贴试验,确定阳性对照物的初步合适浓度区间。然后再选取60名健康受试者根据第一阶段合适浓度范围设计浓度进行第二阶段试验,进一步确定合适浓度。结果:第一阶段的试验提示,阳性基准物的浓度在0.01%~0.05%之间,第二阶段确定0.02%SLS的1级皮肤反应人数≤5例,2级皮肤反应人数2例,该反应率与标准中的阳性结果最为接近。结论:建议以0.02%SLS作为人体单次斑贴试验的阳性对照物基准模型。     

Benchmark for the Coupled Magneto-Mechanical Boundary Value Problem in Magneto-Active Elastomers

Within this contribution, a novel benchmark problem for the coupled magneto-mechanical boundary value problem in magneto-active elastomers is presented. Being derived from an experimental analysis of magnetically induced interactions in these materials, the problem under investigation allows us to validate different modeling strategies by means of a simple setup with only a few influencing factors. Here, results of a sharp-interface Lagrangian finite element framework and a diffuse-interface Eulerian approach based on the application of a spectral solver on a fixed grid are compared for the simplified two-dimensional as well as the general three-dimensional case. After influences of different boundary conditions and the sample size are analyzed, the results of both strategies are examined: for the material models under consideration, a good agreement of them is found, while all discrepancies can be ascribed to well-known effects described in the literature. Thus, the benchmark problem can be seen as a basis for future comparisons with both other modeling strategies and more elaborate material models.     

Development and Validation of a Hospital Indicator of Activity-Based Costs for Injury Admissions

ObjectivesTo develop a hospital indicator of resource use for injury admissions.MethodsWe focused on resource use for acute injury care and therefore adopted a hospital perspective. We included patients ≥16 years old with an Injury Severity Score >9 admitted to any of the 57 trauma centers of an inclusive Canadian trauma system from 2014 to 2018. We extracted data from the trauma registry and hospital financial reports and estimated resource use with activity-based costing. We developed risk-adjustment models by trauma center designation level (I/II and III/IV) for the whole sample, traumatic brain injuries, thoraco-abdominal injuries, orthopedic injuries, and patients ≥65 years old. Candidate variables were selected using bootstrap resampling. We performed benchmarking by comparing the adjusted mean cost in each center, obtained using shrinkage estimates, to the provincial mean.ResultsWe included 38 713 patients. The models explained between 12% and 36% (optimism-corrected r²) of the variation in resource use. In the whole sample and in all subgroups, we identified centers with higher- or lower-than-expected resource use across level I/II and III/IV centers.ConclusionsWe propose an algorithm to produce the indicator using data routinely collected in trauma registries to prompt targeted exploration of potential areas for improvement in resource use for injury admissions. The r² of our models suggest that between 64% and 88% of the variation in resource use for injury care is dictated by factors other than patient baseline risk.     

Quantitative dose–response analysis of ethyl methanesulfonate genotoxicity in adult gpt‐delta transgenic mice

The assumption that mutagens have linear dose–responses recently has been challenged. In particular, ethyl methanesulfonate (EMS), a DNA‐reactive mutagen and carcinogen, exhibited sublinear or thresholded dose‐responses for LacZ mutation in transgenic Muta?Mouse and for micronucleus (MN) frequency in CD1 mice (Gocke E and Müller L [2009]: Mutat Res 678:101–107). In order to explore variables in establishing genotoxicity dose–responses, we characterized the genotoxicity of EMS using gene mutation assays anticipated to have lower spontaneous mutant frequencies (MFs) than Muta?Mouse. Male gpt‐delta transgenic mice were treated daily for 28 days with 5 to 100 mg/kg EMS, and measurements were made on: (i) gpt MFs in liver, lung, bone marrow, kidney, small intestine, and spleen; and (ii) Pig‐a MFs in peripheral blood reticulocytes (RETs) and total red blood cells. MN induction also was measured in peripheral blood RETs. These data were used to calculate Points of Departure (PoDs) for the dose responses, i.e., no‐observed‐genotoxic‐effect‐levels (NOGELs), lower confidence limits of threshold effect levels (Td‐LCIs), and lower confidence limits of 10% benchmark response rates (BMDL₁₀s). Similar PoDs were calculated from the published EMS dose–responses for LacZ mutation and CD1 MN induction. Vehicle control gpt and Pig‐a MFs were 13–40‐fold lower than published vehicle control LacZ MFs. In general, the EMS genotoxicity dose–responses in gpt‐delta mice had lower PoDs than those calculated from the Muta?Mouse and CD1 mouse data. Our results indicate that the magnitude and possibly the shape of mutagenicity dose responses differ between in vivo models, with lower PoDs generally detected by gene mutation assays with lower backgrounds. Environ. Mol. Mutagen. 55:385–399, 2014. © 2014 Wiley Periodicals, Inc.     

Activation of Self-Knowledge Reduces Conflict During Occupational Choice: An ERP Study

We investigated whether the activation of self-knowledge reduces conflict during occupational choice, which can elicit many correct answers. Conflict was measured via event-related brain potentials (ERPs). Results of this study showed that activation of self-knowledge reduces conflict during occupational choice. Our results suggest that, in a situation in which two or more possible correct answers exist, people use self-knowledge as a benchmark to reduce conflict by biasing either choice of behavior.     

Statistical Benchmarks for Health Care Provider Performance Assessment: A Comparison of Standard Approaches to a Hierarchical Bayesian Histogram-Based Method

ObjectiveExamine how widely used statistical benchmarks of health care provider performance compare with histogram-based statistical benchmarks obtained via hierarchical Bayesian modeling.ConclusionsGiven the rewards and penalties associated with characterizing top performance, the ability of statistical benchmarks to summarize key features of the provider performance distribution should be examined.