麻醉期心率变异性的分形特性分析

采用关联维数、分形维数、尺度指数分析38例受试者麻醉期心率变异性信号的分形特性。结果表明:麻醉期心搏周期有显著性的分形特性变化,麻醉状态下心率变异性信号的关联维数(P<0.000001)明显低于清醒状态,而短时程尺度指数α1(P<0.0001)显著性地高于清醒状态。说明了麻醉期心率变异性信号的分形特性有明显地变化,提示运用非趋势波动分析方法分析麻醉期心率变异性信号的分形特性更适合于临床麻醉深度监测。     

分子生药学学科在新“形势”下培养中药材产业人才的教学研究

《中药材保护和发展规划(2015—2020)》和《中医药发展战略规划纲要(2016—2030年)》的发布说明我国中药材产业进入新的、高水平的发展机遇期;另一方面,"屠呦呦"效应不仅助推了该产业的发展,也预示着该产业的国际竞争日渐剧烈。在机遇与竞争高位并存的新"形势"下,中药材产业现代高级技术人员的培养成为中药材产业可持续发展的关键问题之一。作为中药学等相关专业的前沿课程,分子生药学是生药学与分子生物学结合的一门新兴交叉学科,对培养现代中药材产业的高级技术人员显得尤为重要。分子生药学不仅继承传统生药学的观念,弥补其不足,还处于分子生物技术领域的前沿,不断地推陈出新,进而促进生药学的发展。这些也是分子生药学的教学难点,很难有统一的教学模式,因此,该文从全国分子生药学教学的现状、本科生和研究生教育、社会认同、课程自我理论和实践的更新等几个方面阐述可能的教学模式,培养高级中药材产业人才,满足社会和产业发展的需求。     

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??OBJECTIVE To investigate the impacts of particle size and preferred orientation on relative peak intensity, number of peaks and order of peak intensity in powder X-ray diffraction (PXRD) analysis of organic and inorganic pharmaceutical crystalline materials and evaluate the phase identification methods in various pharmaceutical compendiums.METHODS The PXRD patterns of organic and inorganic materials with different particle sizes obtained by sieving or grinding were acquired and the number of diffraction peaks, peak position and intensity of diffraction peaks were compared across different samples. RESULTS Due to preferred orientation effects, the diffraction patterns of samples with different particle sizes were apparently different, including the number of peaks, relative peak intensity and the order of the peak intensity. CONCLUSION Scientists may get different CONCLUSION s from the RESULTS of same tests performed according to the related guiding principles of current Chinese Pharmacopeia and USP39, EP8.0, JP16 ???? pharmacopoeia for identifying the crystalline forms.The phase identification by PXRD method in current Chinese Pharmacopeia neglects the effects of preferred orientation on diffraction peaks and relative peak intensity. This guideline needs to be updated to better reflect the scientific observation in industry and align with other well accepted compendiums such as USP, EP and JP.     

MF-SuP-pKa: Multi-fidelity modeling with subgraph pooling mechanism for pKa prediction

Acid-base dissociation constant (pK_a) is a key physicochemical parameter in chemical science, especially in organic synthesis and drug discovery. Current methodologies for pK_a prediction still suffer from limited applicability domain and lack of chemical insight. Here we present MF-SuP-pK_a (multi-fidelity modeling with subgraph pooling for pK_a prediction), a novel pK_a prediction model that utilizes subgraph pooling, multi-fidelity learning and data augmentation. In our model, a knowledge-aware subgraph pooling strategy was designed to capture the local and global environments around the ionization sites for micro-pK_a prediction. To overcome the scarcity of accurate pK_a data, low-fidelity data (computational pK_a) was used to fit the high-fidelity data (experimental pK_a) through transfer learning. The final MF-SuP-pK_a model was constructed by pre-training on the augmented ChEMBL data set and fine-tuning on the DataWarrior data set. Extensive evaluation on the DataWarrior data set and three benchmark data sets shows that MF-SuP-pK_a achieves superior performances to the state-of-the-art pK_a prediction models while requires much less high-fidelity training data. Compared with Attentive FP, MF-SuP-pK_a achieves 23.83% and 20.12% improvement in terms of mean absolute error (MAE) on the acidic and basic sets, respectively.     

The impact of lipids on the cancer–immunity cycle and strategies for modulating lipid metabolism to improve cancer immunotherapy

Lipids have been found to modulate tumor biology, including proliferation, survival, and metastasis. With the new understanding of tumor immune escape that has developed in recent years, the influence of lipids on the cancer–immunity cycle has also been gradually discovered. First, regarding antigen presentation, cholesterol prevents tumor antigens from being identified by antigen presenting cells. Fatty acids reduce the expression of major histocompatibility complex class I and costimulatory factors in dendritic cells, impairing antigen presentation to T cells. Prostaglandin E2 (PGE2) reduce the accumulation of tumor-infiltrating dendritic cells. Regarding T-cell priming and activation, cholesterol destroys the structure of the T-cell receptor and reduces immunodetection. In contrast, cholesterol also promotes T-cell receptor clustering and relative signal transduction. PGE2 represses T-cell proliferation. Finally, regarding T-cell killing of cancer cells, PGE2 and cholesterol weaken granule-dependent cytotoxicity. Moreover, fatty acids, cholesterol, and PGE2 can improve the activity of immunosuppressive cells, increase the expression of immune checkpoints and promote the secretion of immunosuppressive cytokines. Given the regulatory role of lipids in the cancer–immunity cycle, drugs that modulate fatty acids, cholesterol and PGE2 have been envisioned as effective way in restoring antitumor immunity and synergizing with immunotherapy. These strategies have been studied in both preclinical and clinical studies.     

我院门诊药房智能发药系统持续优化

目的 为了降低门诊药房调配差错率,探讨浙江大学医学院附属邵逸夫医院门诊智能药房发药系统质量优化措施。方法 利用回顾性研究方法,从药品调配数量错误、品种错误2个方面进行分析,提出相应的优化措施,并评价优化措施的效果。结果 优化后的智能发药系统差错发生概率中,数量错误由1.22‰下降到0.55‰,品种错误由0.33‰下降到0.22‰,改善前后有明显的统计学意义（P<0.05）。结论 门诊智能药房是国内医院药学发展新的趋势,最大化地发挥智能药房的优势,必将为临床安全用药和医院药事管理提供更有力的支持。     

非布司他片多条溶出曲线对比研究

目的 通过试验建立有区分能力的溶出曲线测定条件,考察自制片与原研片体外溶出曲线的一致性.方法 分别在美国食品药品监督管理局公布的溶出曲线条件(pH 6.0缓冲液),转速50 rpm和75 rpm,溶出介质900 mL;在不同浓度(0.2%、0.3%、0.5%)十二烷基硫酸钠(SDS)的水溶液,转速50 rpm,溶出介质900 mL;不同pH(1.2、4.5、6.8)缓冲液,转速50 rpm,溶出介质900 mL条件下进行溶出曲线考察.结果 原研片在0.3%十二烷基硫酸钠溶出曲线条件认为有区分能力,自制片与原研片在多条溶出介质中的f2值大于50或15 min累积溶出大于85%.结论 通过试验建立了有区分力的体外溶出曲线条件,试验结果 表明自制片与原研片的溶出行为基本一致,为一致性评价提供试验依据.     

PEO-PPO聚醚嵌段共聚物的表面活性及其在溶液界面的结构

利用和频振动光谱及表面张力测定技术对两亲性聚氧乙烯-聚氧丙烯（PEO-PPO）表面活性剂的表面活性及溶液界面结构进行了研究。结果表明：疏水PPO链段在溶液界面吸附并紧密排列是溶液表面张力降低的主要原因。增加溶液浓度、增大共聚物链内PPO与PEO聚合度比值可增加高分子链在界面的吸附,并使PPO在界面紧密排列,侧基（甲基）有序取向。另外,PPO在分子链中的位置也对这一行为产生影响,PPO位于分子链两端时的结构更有利于PPO在表面紧密堆积,降低界面高分子链间相互作用,减小溶液表面张力。     

阿尔茨海默病与PRNP突变体小鼠动物模型

阿尔茨海默病是由β淀粉样蛋白造成的人类神经损伤性痴呆病之一,目前尚无治疗办法。朊蛋白是β淀粉样蛋白的受体,是阿尔茨海默病发病过程的关键蛋白之一,具有传递神经毒性和保护神经细胞的双重作用。人朊蛋白编码基因（PNRP）多态性影响阿尔茨海默病潜伏期和临床症状,而PRNP突变体小鼠的发现弥补了现有阿尔茨海默病动物模型的不足,并具有在朊蛋白疾病多项研究中的潜在应用价值。本文总结了朊蛋白在阿尔茨海默病病理中的作用及PRNP突变对阿尔茨海默病的影响,并详细总结了PRNP突变体小鼠的发现及在蛋白沉淀样病变研究中的应用和价值,旨在为阿尔茨海默病动物模型研究提供理论参考。