基于网络药理学探讨补肾强督治偻方治疗强直性脊柱炎的作用机理

目的通过网络药理学方法探讨补肾强督治偻方治疗强直性脊柱炎的作用机理。方法运用中药系统药理学成分分析平台(BAT-MAN)数据库获取补肾强督治偻方的作用靶标基因,于CTD数据库中获取强直性脊柱炎疾病相对应的靶标基因,将两者取交集后获取疾病-药物蛋白靶基因,运用网络可视化软件STRING构建蛋白质间相互作用网络,并将结果进行网络可视化展示,通过网络结构和节点间加权重联系的计算分析算法筛选出重要的关键基因。借助DAVID在线工具进行疾病-药物交集靶基因的基因本体论(GO)分析和KEGG通路富集分析。最后在CTD数据库中获取关键基因于强直性脊柱炎的疾病治疗作用。结果补肾强督治偻方靶标基因与强直性脊柱炎疾病靶标基因的交集基因有705个。GO分析结果显示,补肾强督治偻方-强直性脊柱炎交集靶基因的生物功能主要包括基因表达的阳性调控、炎症反应、细胞增殖阳性调控等;信号通路富集结果显示,补肾强督治偻方-强直性脊柱炎交集靶基因的网络主要涉及肿瘤坏死因子信号通路、雌激素信号通路、T细胞受体信号通路等。获得关键基因23个,都与痛症、炎症性疾病及关节炎性疾病相关。结论补肾强督治偻方治疗强直性脊柱炎是多靶点、多通路、多选择的复杂机制过程,其机制多与抗炎和镇痛相关。     

A prognostic signature based on immune-related genes for cervical squamous cell carcinoma and endocervical adenocarcinoma

Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) is the fourth commonest female malignancy worldwide. CESC progresses in immune-microenvironment mainly composed of infiltrating immune and stromal cells. Here, we performed an integrated analysis incorporating the expression profiles from the Cancer Genome Atlas (TCGA) database and scores of immune and stromal cells calculated by Estimation of Stromal and Immune cells in Malignant Tumours using Expression data (ESTIMATE) algorithm. A two-gene signature (CD1C and CD6 genes) was established to predict the prognosis of CESC. Based on this signature, patients were divided into the high- and low-risk groups, and this signature showed good prognostic performance according to the results of Kaplan-Meier analysis and receiver operating characteristic (ROC) analysis in train set and two validation sets. A nomogram was built for evaluating the clinical applicability of this signature. In addition, based on Tumor Immune Estimation Resource (TIMER) database, 2 hub genes showed negative correlations with tumor purity and positive correlations with infiltrating levels of immune filtrating cells. What’s more, we propose new treatment strategies for the two prognostic subtypes. Low- risk patients were found presenting with a higher level of immune checkpoint molecules and showing higher immunogenicity in immunophenoscore (IPS) analysis, which indicated a better response for immunotherapy. Meanwhile, estimated by Genomics of Drug Sensitivity in Cancer (GDSC) database, the high-risk patients showed sensitive responses to five chemotherapy drugs. Finally, 10 candidate small-molecule drugs for CESC were defined. In summary, the CD1C-CD6 signature can accurately predict the prognosis of CESC.     

基于网络药理学和生物信息学方法的白藜芦醇治疗三阴性乳腺癌的机制研究

目的 探索白藜芦醇抗三阴性乳腺癌（triple negative breast cancer,TNBC）的潜在作用机制。方法 利用PharmMapper、SwissTargetPrediction、SuperPred、DrugBank数据库,筛选整合白藜芦醇可能作用的靶点。与CTD、DisGeNET、MalaCards数据库中筛选得到的TNBC靶点相映射后得到白藜芦醇抗TNBC可能作用的靶点。利用DAVID数据库对得到的靶点进行基因功能（Gene ontology,GO）和京都基因与基因组数据库（Kyoto Encyclopedia of Genes and Genomes,KEGG）通路注释分析,利用STRING数据库和Cytoscape软件构建靶点间的蛋白互作网络,筛选出核心靶点及核心模块。结果 共筛选得到422个白藜芦醇可能作用的靶点,1 799个TNBC相关靶点,映射后共得到白藜芦醇治疗TNBC的潜在作用靶点130个,并从中进一步筛选出了10个核心基因（MAPK1、MAPK3、TP53、SRC、PIK3CA、AKT1、PIK3R1、MAPK8、PTPN11、JAK2）,KEGG通路富集提示核心基因主要涉及PI3K-Akt等信号通路。结论 白藜芦醇可能是通过靶向作用于多个靶点及通路,形成相互协调的作用网络从而发挥抗TNBC作用,其中PI3K/Akt通路可能发挥重要作用,为白藜芦醇在TNBC治疗方面的进一步研究提供参考。     

Group sequential designs with prospectively planned rules for subpopulation enrichment

We propose a class of randomized trial designs aimed at gaining the advantages of wider generalizability and faster recruitment while mitigating the risks of including a population for which there is greater a priori uncertainty. We focus on testing null hypotheses for the overall population and a predefined subpopulation. Our designs have preplanned rules for modifying enrollment criteria based on data accrued at interim analyses. For example, enrollment can be restricted if the participants from a predefined subpopulation are not benefiting from the new treatment. Our designs have the following features: the multiple testing procedure fully leverages the correlation among statistics for different populations; the asymptotic familywise Type I error rate is strongly controlled; for outcomes that are binary or normally distributed, the decision rule and multiple testing procedure are functions of the data only through minimal sufficient statistics. Our designs incorporate standard group sequential boundaries for each population of interest; this may be helpful in communicating the designs, because many clinical investigators are familiar with such boundaries, which can be summarized succinctly in a single table or graph. We demonstrate these designs through simulations of a Phase III trial of a new treatment for stroke. User‐friendly, free software implementing these designs is described. Copyright © 2016 John Wiley & Sons, Ltd.     

A Study of Expectations and the Marital Quality of Participants of a Marital Enrichment Seminar

This longitudinal study investigated the effects of expectations of effort of self and spouse on the marital quality of marital enrichment seminar participants. Self‐report measures of marital quality, expectations regarding effort put into implementing what was learned during the seminar, amount of perceived effort, and satisfaction with effort were administered before and after the seminar, as well as at a 2‐month follow‐up. Participants (147 women, 95 men) attended community‐based marital enrichment seminars in 12 U.S. cities. Multivariate path models indicated that larger discrepancies between expectations of effort postseminar and perceived effort at 2‐month follow‐up were associated with less satisfaction with perceived effort. Furthermore, participants' dissatisfaction in their spouses' effort had a negative effect on marital quality while controlling for initial marital quality, whereas dissatisfaction in their own effort did not. These findings highlight the possible detrimental effect that unmet spousal expectations can have. Implications for marital enrichment programs and couples therapy are discussed.     

基于系统药理学探索莪术有效成分的药理作用机制

目的:通过一系列系统药理学方法初步探讨了莪术有效成分的药理作用机制。方法:利用中药系统药理学分析平台(TCMSP)数据库获取莪术中有效成分;从Pharm Mapper Server中获得莪术有效成分的靶蛋白;Uni Prot数据库中获取靶标的基因名称并于CTD数据库中获取基因相对应的疾病;运用网络可视化软件,构建莪术有效成分-靶点-疾病相互作用网络;借助DAVID工具进行莪术有效成分蛋白质群的基因本位论(GO)分析和靶蛋白作用通路的富集分析。结果:文本挖掘结果表明莪术主要相关疾病有肿瘤性疾病、神经系统疾病和代谢性疾病;GO分析结果表明莪术主要通过类固醇激素介导的信号通路、从RNA聚合酶Ⅱ启动子的转录起始、凋亡过程的负调控、肽基络氨酸磷酸化、蛋白质自磷酸化、视黄酸受体信号通路、从RNA聚合酶Ⅱ启动子的转录的正调节等作用发挥生物学功能;信号通路富集结果表明莪术主要作用蛋白与癌症途径,PPAR信号通路,癌症中的蛋白多糖,非小细胞癌,PI3K-Akt信号通路等信号通路有关。结论:莪术可能主要通过调控癌症途径,PPARP,PI3K-Akt信号通路等多途径发挥其药理作用。综合运用系统药理学的方法可以实现快速而全面地分析药物的药理作用。     

阿胶酶解液相对分子质量分布及其补血升白作用

目的:研究阿胶酶解液的相对分子质量分布及其补血、升白的作用。方法:采用TSK-GEL G2000SWXL色谱柱(7.8 mm×300 mm,5μm),流动相0.1 mol·L~(-1)NaCl+0.05%NaN_3+0.1 mol·L~(-1)磷酸盐缓冲液(pH 6.7),流速0.5 m L·min~(-1),检测波长280 nm,对阿胶原液、阿胶仿生酶解液、阿胶胰蛋白酶酶解液进行相对分子质量分布的测定;采用放血法致小鼠血虚模型及环磷酰胺致小鼠白细胞减少模型,观察阿胶酶解液的补血升白作用。结果:阿胶所含蛋白及多肽的相对分子质量6.64×10~4Da,胰蛋白酶酶解液及仿生酶解液的相对分子质量主要集中在3.7×10~3Da左右;阿胶仿生酶解液及胰蛋白酶酶解液可使血虚模型小鼠血红蛋白(Hb),红细胞计数(RBC)水平显著提高,使白细胞减少模型小鼠的白细胞计数(WBC),RBC和Hb水平显著提高。结论:阿胶经酶解后相对分子质量减小且具有显著的补血升白作用,胰蛋白酶酶解与仿生酶解效力大致相当。     

大孔吸附树脂富集纯化珠子参总皂苷的工艺研究

目的:建立大孔吸附树脂富集、纯化珠子参总皂苷的最佳工艺条件。方法:以人参皂苷Re为对照,以总皂苷含量为指标,研究了HPD型大孔树脂吸附和纯化珠子参总皂苷的工艺条件。结果:优化的工艺条件为:样品溶液的浓度为0.13g/mL(生药量/体积);树脂用量为生药量的2倍(质量比);纯化先用水洗至α-萘酚反应呈阴性,改用6BV的60%乙醇洗脱,洗脱速度为2BV/min。结论:HPD-100型非极性大孔树脂对珠子参总皂苷有良好的吸附及纯化性能;本工艺对珠子参总皂苷的纯化收率高且稳定,纯化后总皂苷含量可达60%以上。     

副溶血弧菌和霍乱弧菌合检增菌液pH值和盐度的研究

目的:研究共同增菌液pH值和盐度对副溶血弧菌和霍乱弧菌生长的影响,找出副溶血弧菌和霍乱弧菌共增菌液的最佳pH值和盐度。方法:利用副溶血性弧菌、霍乱弧菌以及杂菌对共同增菌液的pH值和盐度进行实验,通过弧菌显色平板计数验证增菌效果,从而确定两种弧菌的共同增菌液pH和盐度。结果:副溶血性弧菌和霍乱弧菌合检增菌液的最佳条件为pH8.4,盐度2.1%。结论:增菌液pH值和盐度的改变对副溶血性弧菌和霍乱弧菌生长具有一定影响。