芩黄颗粒离心造粒设备调控参数的优化

应用方差分析结果建立了三元相关调控图，在图中安全调控范围，使苓黄颗粒了离心包衣造粒规模生产收率稳定在９０％左右。     

基于网络药理学和分子对接技术探讨玫瑰花黄酮治疗2型糖尿病的作用机制

目的 以网络药理学和分子对接技术作为分析方法，探究<玫瑰花黄酮类成分在防治糖尿病中的作用机制。方法 采用TCMSP、GeneCards和DisGeNET数据库获取活性成分和疾病靶点，并绘制Venny图；使用Cytoscape 3.9.0软件制作靶标图；String构建PPI蛋白网络；DAVID进行GO和KEGG富集分析；SYBYL-X2.0和PYMOL进行分子对接验证及展示。结果 玫瑰花黄酮11个活性成分通过调控207个糖尿病相关的疾病靶点，产生了667对活性成分－靶点关系，其中山柰酚、槲皮素、芹菜素等成分通过调控Pathway in cancer、AGE-RAGE、PI3K-Akt等通路防治糖尿病；分子对接显示活性成分与糖尿病核心靶点具有较好的结合活性。 结论 本研究系统揭示了玫瑰花黄酮防治糖尿病“活性成分－靶点”的复杂关系，为玫瑰花治疗2型糖尿病的作用机制提供了理论依据。     

中药龟板活性部位GC-MS生物活性指纹图谱和应用

目的 探求调控骨髓间质干细胞中药的共性。方法 硅胶柱层析龟板活性部位浸膏，用石油醚-乙酸乙酯作洗脱剂，梯度洗脱，得到16个样品；采用MTT法研究了它们对rMSCs的增殖调控作用，根据总离子图的相似保留时间和相应峰面积，获得促进rMSCs的增殖的指纹图；同样根据它们的总离子图的相似保留时间和相应峰面积也获得了抑制rMSCs增殖的指纹图；用中药龟板提取物有效部位指纹图谱预测中药汤剂“四物汤”和“栽培红厚壳果仁”共7个样品。结果 活性实验结果显示Ts-2、Ts-3、Ts-11、Ts-12、Ts-16能促进rMSCs的增殖作用（P〈0．05）；Ts-4对rMSCs具有明显抑制作用，其他样品对rMSCs的增殖作用不显著（P〉0．05），不具统计学意义；龟板活性部位指纹图谱预测其他中药活性正确率为86％。结论 这种以生物活性为基础的指纹图谱具有科学性，为寻找相似活性的中药提供新思路。     

基于生物信息学方法筛选骨关节炎进展相关关键基因

目的 利用生物信息学方法筛选骨关节炎进展相关的差异表达基因(DEGs)。方法 在基因表达组学数据库(GEO)下载GSE206848数据集，运用GEO₂R在线工具进行分析，并筛选DEGs;利用R语言绘制火山图和热图。然后对DEGs进行GO功能富集分析和KEGG通路富集分析；将获得的DEGs数据导入STRING数据库构建蛋白互作网络(PPI),并通过CytoHubba插件以5种算法取交集筛选关键基因(Hub gene)。结果 经GEO₂R筛选，从GSE206848数据集中获得DEGs 1 592个(545个上调基因、1 047个下调基因)。GO功能富集分析发现，DEGs的生物学过程主要富集在DNA代谢过程的调节、超分子纤维组织的调控、细胞器组织的负调控；细胞定位主要富集细胞边缘、肌动蛋白细胞骨架、核散斑；分子功能主要富集微管蛋白结合、蛋白丝氨酸/苏氨酸激酶活性、蛋白丝氨酸/苏氨酸/酪氨酸激酶活性。KEGG通路富集分析结果主要涉及PI3K-Akt信号通路、肌动蛋白细胞骨架调控等。应用CytoHubba插件筛选得到3个关键基因(PIK3CA、EGFR...     

表观遗传修饰在肿瘤代谢重编程中的作用和机制★

代谢重编程和表观遗传修饰是肿瘤的重要特征。在肿瘤发生发展过程中，肿瘤细胞改变其新陈代谢途径，表现出可调控的代谢可塑性。肿瘤代谢的改变在很大程度上受到表观遗传修饰的调控，比如，表观遗传修饰酶的表达或活性改变可能对肿瘤代谢产生直接或间接的影响。因此，探讨表观遗传修饰在肿瘤代谢重编程过程中的调控作用，对于深入理解肿瘤的致病机制具有重要意义。本文主要探讨了表观遗传修饰调控肿瘤代谢重编程的最新研究发现，包括DNA甲基化、组蛋白修饰、染色质重塑和非编码RNA对肿瘤代谢重编程的调控，并展望了基于表观遗传修饰调控的肿瘤代谢重编程的治疗前景。     

几种调控基因对除虫链霉菌工业生产株的抗生素效价的影响

在模式链霉菌（如天蓝色链霉菌和变铅青链霉菌）中导入许多抗生索生物合成的调控基因可以大幅度提高抗生索的含量。本文报道利用链霉菌的整合质粒克隆几种已知的调控基因。并通过接合转移从大肠埃希菌中导入产生avermectin和多拉菌素的除虫链霉菌工业生产菌株中。发现3种调控基因afiR、aveR和orfX对菌株MMR630中avermectin的含量均可以提高约1倍。但是，以上的3种，加上另外3种调控基因分别导入菌株G11后，发现除aft8提高约13％外，其余调控基因使菌株产生多拉菌素的含量反而有不同程度的降低。将调控基因币B置于链霉菌强启动子PerrnE^＊下表达降低了菌株G11中多拉菌素的含量。上述结果表明，调控基因对不同链霉菌的抗生素生物合成具有不同的影响，反映了抗生素生物合成确实受到了复杂网络的调控。     

核受体介导的摄入型转运体转录调控对化疗药物药效的影响

核受体作为主要的转录调控因子对生物体内药物转运体的基因表达起到关键的调控作用。近年的研究发现，核受体介导的药物转运体过表达与化疗药物多药耐药密切相关，在研究外排转运体介导的多药耐药的同时，与摄入型转运体相关的肿瘤耐药也逐渐进入了研究者的视线。鉴于核受体对药物转运体转录调控的重要意义，有必要对其导致的摄入型转运体转录失调进行深入地探讨。本文从核受体调控角度出发，综述了核受体对摄入型转运体基因表达调控机制的研究进展，从而为提高化疗药物敏感性和逆转化疗药物的多药耐药提供一种新思路。     

基因组特定基因座相关蛋白的纯化

真核生物的DNA在染色质中被多种蛋白复合体结合及调控，本文介绍了一种叫做离体染色质片段蛋白组学（proteomics of isolated chromatin segments，PICh）的方法来解析调控特定基因座的蛋白。PICh利用一种特殊的核酸探针来分离鉴定结合基因组DNA的蛋白。利用PICh法从人端粒染色质上纯化鉴定出了大多数已知的端粒因子，并发现了大量新的调控蛋白。     

Bcl-2家族与脑缺血/再灌注后神经细胞凋亡

脑缺血再灌注损伤（cerebral ischemia reperfusion injury，CIRI）的机制研究经历了从器官水平到分子水平的不断深化过程．认为细胞凋亡与缺血再灌注损伤密切相关。细胞凋亡（apoptosis）又称程序性细胞死亡（programmed cell death，PCD），是受基因调控的细胞主动自杀过程。CIRI可诱导多种凋亡调控基因表达。包括促凋亡基因和抑凋亡基因．这些基因编码的蛋白质产物可直接或间接参与凋亡的调控。Bcl-2家族在细胞凋亡调控过程中起重要作用，目前研究也较为深入。     

关于插图制作的要求

按插图在文中出现的先后顺序连续编码，如图1、图2，……。每个插图均应冠有图题，说明性的资料应置于图的下方注释中。请用计算机扫描或制图，图像要求有良好的清晰度和对比度，需要标注的符号（包括剪头）请在图中一一标出。图序、图题要明白清晰。图的上下方向要明确清楚，切勿颠倒。如是人物肖像，应征得本人的书面同意。大体标本照片在图内应用具体的尺度标记，     

Solid dispersion of pharmaceutical ternary systems I: Phase diagram of aspirin-acetaminophen-urea system

The phase diagram of an aspirin-acetaminophen-urea system was constructed. The data obtained by the thermomicroscopic method showed that the binary systems of aspirin-acetaminophen, aspirin-urea, and acetaminophen-urea are simple eutectic mixtures with negligible formation of solid solutions or molecular compounds. The equilateral triangular phase diagram of the ternary system revealed that it forms, upon solidification, solid dispersions of the mechanical mixture type. The ternary eutectic corresponded to a composition of 60% aspirin, 20% acetaminophen, and 20% urea at 72 degrees. The method of calculating the composition finally solidified melts, lying within any area of the phase diagram, is presented. Use of the phase diagram in selecting the optimum ratio of components to enhance dissolution rates of these drugs may be possible.     

Thermal Analysis of the Tertiary Butyl Alcohol-Water System and Its Implications on Freeze-Drying

Utilizing differential scanning calorimetry (DSC) for tertiary butyl alcohol (TBA) solutions a phase diagram was constructed for the TBA-water system. By utilizing thermal treatment during the DSC measurements the metastable states were eliminated. The phase diagram fit that for a congruently melting compound in which compound formation occurred with a maximum at 70% TBA representing pure TBA hydrate. Two eutectics occurred at 20% (Eutectic A) and 90% (Eutectic B). A freeze-drying microscope revealed that TBA altered the crystal habit of ice. A concentration of 3% TBA was required before large needle-shaped ice crystals became evident. The addition of 10% TBA to the system resulted in even finer needle-shaped ice crystals. At the eutectic compositions (20% and 90% TBA), the frozen eutectic mixture could not be resolved with the microscope because eutectic crystals are very small. The 70% TBA solution, which corresponds to the melting of pure TBA hydrate, formed very large hydrate crystals. The rate of sublimation of the TBA and water molecules was found to be concentration dependent. At concentrations below 20% TBA (water rich portion of the phase diagram) water molecules sublimed faster while at concentrations above 20% TBA (TBA rich portion of the phase diagram) TBA molecules sublimed faster. At the eutectic A composition, both TBA and water molecules sublimed at the same rate. This may be because all of the TBA molecules are strongly associated with each other in the form of a clathrate hydrate.     

基于帕累托图及鱼骨图分析的医院中药饮片代煎服务质量提升的探索与实践

目的探索帕累托图及鱼骨图分析法在提升医院中药饮片代煎服务质量中的作用。方法制作医院中药饮片代煎服务质量问题登记表,统计河南省洛阳正骨医院 2020年 1—6月(整改前)的中药代煎服务过程中出现的质量问题及类型,利用帕累托图及鱼骨图分析法,确定中药代煎服务质量问题的主要类型,找出根本原因,制定相关整改措施,持续质量改进。比较整改前与 2020年 7—12月(整改后)服务质量差异。结果整改前中药代煎服务处方 7 106张,出现服务质量问题 479例,整改后中药代煎服务处方 9 879张,出现服务质量问题 184例,帕累托图分析显示,中药代煎服务问题的主要类型为:煎药量误差(24.22%)、药味 /颜色差异(18.16%)、未核对处方药物(15.87%)、特殊煎煮方法未标识(11.06%)、未对病人进行用药指导( 10.23%);经整改后,中药代煎服务人次增加,服务质量问题发生率由管理前的 6.74%下降为 1.86%,各类型服务质量问题发生率均有下降,其中下降最为明显的为煎药量误差;煎药人员中药代煎综合服务能力评分由管理前的(7.58±2.43)分提升为管理后的(11.17±1.34)分(P<0.01)。结论利用帕累托图及鱼骨图分析方法可以有效提高煎药人员工作技能及效率,保障中药饮片代煎服务质量。     

某三甲医院门诊不合理用药处方Pareto图分析

目的分析某三甲医院门诊处方,确定不合理用药情况及类型,为进一步提高合理用药水平提供参考。方法以该院2018年6月至2019年5月门诊处方为对象,采用人工点评方式对处方的合理性进行评价,并通过Pareto图分析造成门诊处方不合理用药的主要、次要及一般因素。结果2018年6月至2019年5月期间,随机提取该院门诊处方共计23658张,不合理用药处方1022张,占4.32%。不合理用药的主要因素为适应证不适宜、临床诊断书写不全;次要因素为用法用量不适宜;一般因素为医师未按规定开具抗菌药物、临床诊断不规范、联合用药不适宜、药品剂型或给药途径不适宜、遴选药品不适宜、重复给药、超禁忌用药。结论通过Pareto图对门诊不合理用药处方进行分析,有利于确定该院门诊不合理用药处方存在问题的主要因素和次要因素,从而有针对性地实施药学干预,提高临床用药的合理性。     

不同方法制备枸杞籽油微乳的比较研究

目的:优选枸杞籽油微乳的处方组成,比较枸杞籽油微乳的3种制备方法。方法:以枸杞籽油自身作为油相,利用外观、乳滴粒径、三元相图和伪三元相图等评价指标,优选枸杞籽油微乳的制剂处方;以乳滴粒径和粒度分布为指标,比较超声乳化法、高压乳匀法和自乳化法制备枸杞籽油微乳的不同特点。结果:优选的处方为1%枸杞籽油、1%吐温80、2%甘油;超声乳化法的工艺参数为超声功率480W,工作-间歇时间为10s-5s,超声时间25min,制得微乳的平均粒径为(74.6±45.3)nm(多分散系数(P.I)=0.368);高压乳匀法的工艺参数为均质压力500bar循环3次,制得微乳平均粒径为(69.0±31.5)nm(P.I=0.378);在相同处方比例下,自乳化法无法自发形成微乳,而当枸杞籽油:吐温80:甘油=1:7:2时,可自发形成微乳。结论:不同方法均能制得粒径小而均匀、外观透明有乳光的枸杞籽油微乳,但各法适用范围和特点不同。     

Synthesis of Caffeine/Maleic Acid Co-crystal by Ultrasound-assisted Slurry Co-crystallization

A green approach has been used for co-crystallization of noncongruent co-crystal pair of caffeine/maleic acid using water. Ultrasound is known to affect crystallization; hence, the effect of high power ultrasound on the ternary phase diagram has been investigated in detail using a slurry co-crystallization approach. A systematic investigation was performed to understand how the accelerated conditions during ultrasound-assisted co-crystallization will affect different regions of the ternary phase diagram. Application of ultrasound showed considerable effect on the ternary phase diagram, principally on caffeine/maleic acid 2:1 (disappeared) and 1:1 co-crystal (narrowed) regions. Also, the stability regions for pure caffeine and maleic acid in water were narrowed in the presence of ultrasound, expanding the solution region. The observed effect of ultrasound on the phase diagram was correlated with solubility of caffeine and maleic acid and stability of co-crystal forms in water.     

Phase diagram studies for microencapsulation of pharmaceuticals using cellulose acetate trimellitate

Phase diagrams were prepared to indicate the region of microcapsule formation for the following system: cellulose acetate trimellitate, light mineral oil, and the solvent mixture (acetone:ethanol), using chloroform as the hardening agent. The effect of sorbitan monoleate, sorbitan monolaurate, and sorbitan trioleate on the region of the phase diagram for the formation of microcapsules was investigated. The results indicate that microcapsules are readily formed when the polymer concentration is in the 0.5-1.5% range and the solvent concentration is in the 5-10% range. Aggregation of microcapsules was minimized by using lower solvent concentration. Low concentrations of sorbitan monooleate in mineral oil (less than or equal to 1%) gave products that had smoother coats and more uniform particle size. Surfactants with low hydrophile:lipophile balance produced larger regions on the phase diagram for microencapsulation compared with a surfactant with higher hydrophile:lipophile balance. A mechanism for microencapsulation is described. Tartrazine microcapsules produced using different concentrations of surfactant were tested for dissolution characteristics in both acidic and neutral conditions. Tartrazine-containing microcapsules prepared by using 3% sorbitan monooleate had the lowest release in acidic conditions. The effect of surfactant and formulation concentration on microcapsule size was studied by analyzing the particle size distribution for both blank and tartrazine-containing microcapsules. The smallest microcapsule size was obtained when the sorbitan monooleate concentration was 3%. It appears that there is an upper limit for the surfactant concentration that could be used to achieve successful microencapsulation.     

甲苯咪唑-倍他环糊精包合物相溶解度图的绘制

通过测定甲苯咪唑在不同浓度的倍他环糊精溶液中的溶解度,绘制溶解度曲线,得到的相溶解度图为Ｂｓ型,并由此求出包合物的表观稳定常数为３９．５８。     

Study of the Interaction of Dithranol with Heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin in Solution and in the Solid State

The interaction between dithranol and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TMBCyD) has been investigated in aqueous solution containing isoascorbic acid (0·2% w/v) as antioxidant and in the solid state. The interaction in the solid state was studied by differential scanning calorimetry (DSC), infrared spectroscopy (IR), X-ray powder diffractometry (XPD) and a dissolution-rate method. The extent of complexation between the two substances was poor, as indicated by the low value of the slope of the linear part of the solubility curve. A phase diagram was constructed by measuring the thermal behaviour of various re-solidified physical mixtures of dithranol and of TMBCyD previously subjected to heating until melting of the TMBCyD. The loss of dithranol, owing to sublimation and degradation caused by the thermal treatment used, was less than 10%. In keeping with XPD and IR data, the phase diagram indicated that a complex was formed containing 13·7% dithranol (molar ratio 1:1) which had a congruent melting point at 164°C. The drug dissolution rate from the 1:1 complex was measurable, unlike that of the corresponding physical mixture, and was significantly increased when the complex was dispersed in the glassy matrix of TMBCyD, as it was in re-solidified mixtures containing 2–7% dithranol. The results show that the solubility of dithranol is increased significantly as a consequence of its interaction with TMBCyD, despite the low extent of complexation between the two substances.     

品管圈在降低我院门诊药房药品过期损耗中的应用

目的：探讨品管圈活动对降低药品过期造成的药品损耗的效果。方法：成立品管圈,按照品管圈的步骤实施各项活动,运用头脑风暴法分析产生药品过期损耗高的原因,采取鱼骨图及关联图手法探讨解决的对策并实施,评价有形成果（过期药品报损率）,采用雷达图评价无形成果（圈能力）。结果：我院过期药品损耗率高的主要原因是医生获得药品信息不畅,药师工作有疏漏,频繁更换药品规格、厂家、批号及商业配送近效期药品等。针对上述原因制定了相应的工作制度及多项措施,并纳入药品养护的工作流程。定期组织对医生、药师进行业务知识、相关制度强化培训等有效措施。活动后成效显著,过期药品报损率由0.230%降低至0.021%。药师在品管圈手法、责任感、团队精神、沟通及协调能力等方面都有大幅度提高。结论：品管圈活动对我院降低药品过期报损率发挥了重要作用。