Experimental Study on the Effect of Sanchong Banxia Baizhu Tianma Decoction on the Expression of 5-HT1B/1D Receptor in the Brain of Rats with Migraine

目的探索三虫半夏白术天麻汤治疗偏头痛的作用机制。方法建立硝酸甘油致大鼠偏头痛模型,给予半夏白术天麻汤高、中、低剂量灌胃干预7 d,以苯甲酸利扎曲普坦为西药阳性对照药物,并予空白组、模型组进行对照。运用RT-PCR检测5羟色胺1B、1D(5-HT1B/1D)受体的基因表达。结果 1)对5-HT1B受体表达的影响:与空白组相比,模型组显著低于空白组(P0.05),中药中剂量组、中药高剂量组、西药组及联合用药组显著低于空白组(P0.05)。2)对5-HT1D受体表达的影响:与空白组相比,中药中剂量组显著降低(P0.05);与模型组相比,各组无显著差异(P>0.05);与中药中剂量组相比,空白组、中药低剂量组、西药组、联合用药组较中药中剂量组显著升高(P0.05)。结论 5-HT1B/1D受体调节异常为偏头痛的发病环节之一。三虫半夏白术天麻汤可以提高偏头痛大鼠脑组织5-HT1B受体的基因表达,对5-HT1D受体的基因表达具有双向调节作用,临床运用,剂量不宜过大。Objective: To explore the mechanism of Sanchong Banxia Baizhu Tianma Decoction in the treatment of migraine. Methods: Migraine model of SD rats were set up with nitroglycerin,given Banxiabaizhutianma decoction of high,medium and low-dose intervention respectively for 7 days,taking Rizatriptan Monobenzoate as a positive control drug medicine,compared with the blank control group and the model group. RT-PCR was used to test the genetic expression of the 5-HT1 B receptor and the 5-HT1 D receptor. Results: The influence on the expression of the 5-HT1 B receptor: compared with the blank control group,the model group was significantly lower than the control group(P 0.05);traditional Chinese medicine medium dose group,high dose group,western medicine group and the combination group were significantly lower than the blank control group(P 0.05). The influence on the expression of 5-HT1 D receptor:compared with the blank control group,traditional Chinese medicine medium dose group decreased significantly(P 0.05);compared with the model group,there was no significant differ ence among them(P > 0.05);compared with the traditional Chinese medicine medium dose group,the blank control group,traditional Chinese medicine low dose group,western medicine group and combination group were significantly higher(P 0.05). Conclusion: 5-HT1B/1D receptor dysregulation is one cause of the pathogenesis of migraine. Sanchong banxia baizhu tianma decoction can improve the genetic expression of 5-HT1 B receptors in migraine rats′ brains,and has a dual-direction regulation on genetic expression of the 5-HT1 D receptors. In the field of clinical application,the dose should not be too large.2012福建省中医药科研课题(wst201211

The effection of everolimus on hamster-to-rat concordant heart xenotransplantation

背景：器官移植是解决很多终末期疾病最有效的手段，然而器官短缺限制着器官移植术的推广。异种移植是最有可能快速解决器官短缺问题的途径之一。虽然异种移植的超级性排斥反应已经因分子生物学技术的应用而极大减轻，但异种移植的急性排斥反应、延迟性排斥反应等仍旧没有克服。新型免疫抑制剂的开发可能有助于克服这些类型的免疫排斥反应。依维莫司是雷帕霉素衍生物，是一种可用于抗移植排斥的免疫抑制药物，动物实验和临床资料表明它可延长同种器官移植物生存期。依维莫司对免疫系统具有多种调节作用。然而关于依维莫司对异种移植作用的研究目前尚属空白。 目的：本实验在体外研究免疫抑制剂依维莫司对T细胞的免疫抑制作用，在体内研究依维莫...Background: Organ transplantation is the most efficient method to solve end-stage disease. Howeve, the organ shortage has resulted in restriction of promotion of transplantation. Xenotransplantation is one of the most possible approach to solve the organ shortage problem. Although hyperacute rejection of xenotransplantation has already alleviated to a great extent with the application of molecular...学位：医学硕士院系专业：医学院_外科学学号：2452013115349

Effect of MS-275 combined with cisplatin on ErbB3-overexpressing human bladder transitional cell carcinoma, and its clinical prospect

摘要 第一部分MS-275联合顺铂对ErbB3过表达膀胱尿路上皮癌细胞的杀伤作用及机制研究 目的 ErbB3是表皮生长因子受体（ErbB/HER）家族的一员，其在肿瘤的发生发展过程中起着重要的作用。我们的前期研究通过慢病毒转染的方式获得了ErbB3过表达的人膀胱尿路上皮癌（BTCC）细胞株，并发现ErbB3过表达的人膀胱尿路上皮癌细胞株会对顺铂（DDP）等化疗药物产生耐药。有研究表明MS-275可抑制ErbB3蛋白在ErbB2过表达的人乳腺癌细胞中的表达并促进其凋亡。本研究使用MS-275及DDP单药和联合用药处理，观察MS-275和DDP对ErbB3过表达的人膀胱尿路上皮癌细胞株的杀伤...Abstract Part one: Effect of MS-275 combined with cisplatin on ErbB3-overexpressing human bladder transitional cell carcinoma, and its underlying mechanism. Objective: ErbB3 is a member of the epidermal growth factor receptor（ErbB/HER）family, which plays an important role in the development and progression of the tumor. Our previous study obtained the ErbB3-overexpressing human bladder uroth...学位：医学硕士院系专业：医学院_外科学学号：2452014115355

Effects of Recombinant Human Endostatin and Docetaxel on MMP and its Following Anti-neoplastic Effect under Different Administration Sequences

Background and objective The aim of this study is to observe the changes of MMP-2 and its regulators, and to investigate the mechanism of the two administration sequences of recombinant human endostatin (rh-endostatin) and docetaxel. Methods The experiment was performed as 2 stages. Firstly, nude mice with xenograft tumor were randomized into 2 groups as rh-endostatin-treated group with rh-endostatin 400 μg•d-1, d1-d14 and docetaxel-traeted group with docetaxel 10 mg•kg-1•3d-1, d1-d14. Secondly, nude mice with xenograft tumor were randomized into 3 groups as concurrent administration group (rh-endostatin 400 μg•d-1, d1-d35, docetaxel 10 mg•kg-1•3d-1, d1-d19), endo-first group (rh-endostatin 400 μg•d-1, d1-d35, docetaxel 10 mg•kg-1•3d-1, d16-d34) and model group (positive control, mice burdened tumor without treatment). The volume of tumor was measured during treatment. Detection of the expressions of MMP-2, TIMP-2, EMMPRIN and the count of microvessel density (MVD) by immunohistochemistry stain examination were carried out at the end of experiment. Results Compared with the docetaxel-treated group, more obvious down-regulation of expression of MMP-2, EMMPRIN (P=0.024, P=0.081) were observed in rh-endostatin-treated group. No significant difference was found in TIMP-2 expression between the 2 groups. In combined treatment groups, at the endpoint tumor volumes of concurrent administration group and the endo-first group were remarkably smaller than that in model group (P<0.001, P=0.003). According to the administration procedure, concurrent administration inhibited tumor growth stronger than endo-first treatment did. Both of the combined groups down-regulated the expression of MMP-2 and decreased microvessel density (P<0.05). Compared with model group, the expression of TIMP-2 was upregulated (P=0.001) as well as EMMPRIN down-regulated (P=0.018) in concurrent adminis-tration group. Oppositely, the same results were not observed in the endo-first group. Conclusion The schedule of the concurrent administration group could inhibit the tumor growth better, and it down-regulated MMP-2 expression through TIMP-2 and EMMPRIN, and thus slow down the tumor growth superiorly to another schedule of treatment

住院患者华法林与其他药物联用对抗凝作用的影响研究

目的探讨华法林在对住院患者行抗凝治疗时联用其他药物对抗凝作用的影响及处理方法。方法收集某院2014年1月—2016年12月服用华法林的住院患者病历信息,以华法林的药品说明书和《华法林抗凝治疗的中国专家共识》为参考依据,总结出可能与华法林存在药物相互作用的药品,分析可能由于药物相互作用导致出血的不良反应发生情况,重点监测平均每日国际化标准比值(INR)增加>0.50的患者及INR>3.00的患者。结果使用华法林患者48例。合并用药情况:应用可能增强华法林作用的药物15种(如左氧氟沙星、阿司匹林肠溶片、阿托伐他汀钙片等),可能减弱华法林作用的药物4种(如氢氯噻嗪片、螺内酯片等);未与19种药品合并用药的有7例;存在1种合并用药的有10例,存在2种合并用药的有8例,存在3种合并用药的有11例,存在4种及以上合并用药的有12例。43例患者进行了INR监测,INR平均监测次数为(3.2±1.4)次,其中10例患者平均每日INR增加>0.50,导致出血的患者有6例,涉及药物共8种。结论华法林是一个比较特殊的抗凝药品,可能增强华法林作用的药物有左氧氟沙星、阿司匹林肠溶片、阿托伐他汀钙片等,可能减弱华法林作用的药物有氢氯噻嗪片、螺内酯片等,应加强INR监测,及时调整用药方案,提高临床用药的安全性与合理性

舒林酸衍生物K-80003与MEK抑制剂考比替尼联合用药对乳腺癌的效果研究

目的舒林酸衍生物K-80003是全球首个以类维甲酸受体的截断形式(该文简称tRXRα)为靶点的原创候选新药。本课题组前期研究发现,K-80003在抑制乳腺癌的同时,在乳腺癌细胞中可以激活p-ERK,因此该文试图将K-80003与已上市的MEK抑制剂考比替尼(cobimetinib,GDC-0973)联合使用,探究其对乳腺癌的抑制效果是否增强。方法采用Western blot法、MMTV-PyMT乳腺癌转基因小鼠模型、免疫组化染色等方法,检测K-80003与GDC-0973联合用药对乳腺癌细胞内ERK信号通路及肿瘤细胞凋亡水平的影响。结果 K-80003与GDC-0973联合使用可以更好地抑制p-ERK,并促进PARP切割,导致乳腺癌细胞凋亡,K-80003与GDC-0973联合使用相比于K-80003单药使用,对肿瘤细胞增殖的抑制作用有明显统计学意义。结论舒林酸衍生物K-80003与MEK抑制剂GDC-0973联合使用呈现一定的协同促进乳腺癌细胞凋亡作用。国家自然科学基金资助项目(No 91429306

住院患者华法林与其他药物联用的相互作用研究

目的 探讨华法林在抗凝治疗时联用其他药物引起国际化标准比值(INR)变化的原因及处理方法。方法 收集某院2014年1月—2016年12月服用华法林的住院患者病历,以华法林的药品说明书和《华法林抗凝治疗的中国专家共识》为参考依据,总结出可能与华法林存在药物相互作用的药品,分析可能由于药物相互作用导致出血的不良反应发生情况,重点监测平均每日INR增加>0.50的患者及INR>3.0的患者。结果 使用华法林患者48例。合并用药情况:应用可能增强华法林作用的药物15种,可能减弱华法林作用的有4种;未与19种药品合并用药的有7例;存在1种合并用药的有10例,存在2种合并用药的有8例,存在3种合并用药的有11例,存在4种及以上合并用药的有12例。43例患者进行了INR监测,INR平均监测次数为(3.2±1.4)次,其中10例患者平均每日INR增加>0.5,导致出血的患者有6例,涉及药物共8种。结论 华法林是一个比较特殊的药品,在使用与华法林有相互作用的药物时要考虑其对抗凝治疗的影响,加强INR监测,及时调整用药方案,提高临床用药的安全性与合理性

门诊抗菌药处方调查及合理性分析

采用回顾性分析法,分层随机抽取2014年1月1日~12月31日使用抗菌药物的处方3600张,统计抗菌药应用品种、用药频度、联合用药、使用方法,并对抗菌药处方进行合理性分析。口服给药的处方占87.72%,注射给药处方占12.28%;单品种用药占83.67%,联合用药占16.33%;抗菌药处方合格率为95.08%

Recombinant IL-33 prolongs leflunomide-mediated graft survival through reducing Th1-type cytokine IFN-γ and expanding CD4+Foxp3+ regulatory T cells (Treg) in concordant heart transplantation

摘要 背景 白细胞介素33是一种非典型的IL-1家族成员。IL-33的给药与Th2型（Th2细胞）的应答促进相关联，其通过促进Th2细胞的活性和Th类型2相关的细胞因子，在体内，特别是以IL-4和IL-5的增殖为代表。最近，在同种异体心脏移植，IL-33显示出其能增加小鼠体内的CD4+Foxp3+调节性T细胞（Treg细胞），并抑制Th1型相关细胞因子IFN-γ的水平。我们采用小鼠到大鼠协调性异种移植模型，我们推测，IL-33和来氟米特可以延长移植物的存活。在这个模型中，异种移植物经受急性体液性异种移植排斥反应（AHXR）几乎全部是在第3天，由于细胞介导的排斥反应大约是在第7天，如果通过用...ABSTRACT Background Interleukin-33 is an atypical IL-1 family member. IL-33 administration is associated with facilitation of Th type-2(Th2) responses, typified by promoted Th2 cellactivity and proliferation of type 2-associated cytokines, particularly IL-4 and IL-5 in vivo. Recently, in allogeneic heart transplantation,IL-33 was shown to increase CD4+Foxp3+ regulatory T cells (Treg) in mice,a...学位：医学硕士院系专业：医学院_外科学学号：2452012115316

Maintenance of Long-term Tolerance by T Regulatory Cells in a Mouse Model of Heart Transplantation

目的：自20世纪以来，临床上心脏移植的一年生存率已经达到90%，但是移植后的慢性排斥以及长期存活仍面临巨大挑战，目前临床上所用的免疫抑制剂多数都必须终身用药，从而会产生多种副作用，危害受者的健康，影响患者的生活质量，所以如何诱导移植物的长期耐受是器官移植面临的重大难题。调节性T细胞是具有免疫调节功能的T细胞亚群,在移植后诱导和维持免疫耐受方面发挥重要作用。其中，CD4+CD25+Foxp3+T细胞（CD4+Foxp3+Treg）主要通过细胞接触发挥调节作用，而CD4+IL-10+IL-4-T细胞(Tr1)主要通过分泌抑制性细胞因子IL-10发挥作用。本文首次在小鼠同种异体心脏移植模型中，研究通...Background:In most experimental model of transplantation, the heart and lung allograft are called “tolerance resistant”organs (compared with the ”tolerance prone”organs). It’s reported the one-year survival of heart transplantation have been obviously improved from the 2000s, but long-term tolerance is still a major challenge. The abuse of immunosuppressive drugs, the side...学位：理学硕士院系专业：医学院_生理学学号：2452012115315