Research on the effect of DHA on glucose metabolism in human lung cancer cells and its anti-tumor mechanism

研究背景及目的： 肺癌是人类最常见的恶性肿瘤之一，尽管近年来治疗取得了很大进展，治疗效果仍然较差。癌细胞具有偏向通过糖酵解方式来进行糖代谢获得能量的代谢特征使得肿瘤细胞能够比正常细胞具有更强的葡萄糖代谢能力，为肿瘤细胞的快速增殖与生长提供了能量来源，也使其具备更强的凋亡抵抗能力。天然产物凭借其来源广泛、类型多样、不良反应小，具有开发为化疗药物增效减毒辅助药物的潜力等特点备受关注。双氢青蒿素是青蒿叶中分离的有效抗疟成分，体内代谢活性产物为双氢青蒿素。药物学研究证实青蒿素类药物具有抗疟、抗血吸虫、调节免疫等功能。近年研究发现青蒿素类药物具有抑制乳腺癌、宫颈癌、肝癌及胰腺癌生长作用。然而双氢青蒿素...Abstract BACKGROUND AND OBJECTIVE: Lung cancer is the most common malignant tumor and the leading cause of cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Resistance of NSCLC cells to apoptosis is a major obstacle in anticancer treatment. A unique characteristic of many tumor cells is increased glucose uptake and elevated aerobic ...学位：博士后院系专业：生命科学学院_肿瘤学学号：201317007

Artemisinin and malaria: Current understandings of drug activation, action, and resistance

如能及早确诊并合理救治,疟疾是可以通过抗疟药来治愈的.然而,抗药性疟原虫通常在一种新型药物的大规模使用后的数年内就会出现.随着疟原虫几乎对所有类; 型的抗疟药均产生了不同程度的抗性,青蒿素类药物联合疗法(ACTs)也由此成为治疗疟疾最重要的手段.不幸的是,已有报道称在东南亚地区采用青蒿素或A; CTs治疗后出现了延迟原虫清除的现象,这也让研究者们对青蒿素及其衍生物治疗在未来发生完全失效的可能感到担忧.本文简要综述了青蒿素的药物激活、作用; 机理、药物靶点及可能的抗药性机制等研究的进展;对抗药性的定义、青蒿素组合用药中伴侣药物的选择,以及当前为消除疟疾采取全民用药的努力等问题作了讨论; .与此相关的议题已有大量的研究和文献报道,由于篇幅有限未能逐一列举.此外,本文所讨论的某些问题仍存争议、还需深入的研究方能解答.Malaria is a disease that can be cured with antimalarial drugs if; treated early and appropriately. However, parasites resistant to a new; drug generally emerge within a few years after large-scale applications.; Artemisinin (ART or Qinghaosu) combination therapies (ACTs) have become; the major treatments for malaria after the emergence of parasites; resistant to almost all classes of antimalarial drugs. Parasites with; delayed parasite clearance (DPC) after ART or ACT therapies have also; been reported in Southeast Asia, raising concerns of total failure of; ART and its derivatives. Many classes of antimalarial drugs have been; introduced to successfully treat malaria infections, including; chloroquine, piperaquine, primaquine, mefloquine (MQ), pyrimethamine,; sulfadoxine, ART and derivatives, etc. Regrettably, many of these drugs; have been abandoned by many countries in malaria endemic regions due to; the emergence of drug resistant parasites. According to World Health; Organization, parasite responses to a drug can be classified into four; categories (S, RI, RII, and RIII): Sensitivity (S) to a drug is defined; as clearance of asexual parasitemia within seven days of the first day; of treatment without recrudescence; Resistance RI is defined as; clearance of asexual parasitemia as in sensitive parasites, followed by; recrudescence; RII resistance is indicated by marked reduction of; asexual parasitemia, but no clearance; and RIII resistance shows no; marked reduction of asexual parasitemia. Currently, RII and RIII; resistance to chloroquine, pyrimethamine, and other drugs have been; widely reported; but residence to ART remains largely at R1 level. ART; resistance was initially defined as parasites with half parasite; clearance time (PC1/2)>5 h under a standard ART treatment regimen; (three-day artesunate treatment at 2-4 mg kg-1 d-1). A second; measurement is in vitro ring survival assay (RSA) that was developed; based on the observation that the ring stages of some parasite strains; could survive a short period of ART treatment. Another indicator of; increasing ART tolerance is the elevated rate of recrudescence after ART; or ACT treatments. The generation of highly reactive radicals via; endoperoxide cleavage is critical for ART activation. Both free ferrous; iron and heme have been proposed to be the predominant iron sources for; ART activation. The heme required for ART activation can be derived from; the parasite's heme biosynthesis pathway at the early ring stage and/or; from hemoglobin digestion at later stages. A large number of parasite; molecules have been found to bind or interact with ART, most notably the; Plasmodium falciparum ATPase 6 (PfATP6 or SERCA),; phosphatidylinositol-3-kinase (PfPI3K), chloroquine resistance; transporter (PfCRT), and multiple drug resistance 1 (PfMDR1). Recently,; a gene encoding a parasite Kelch protein (K13) with a six-blade; propeller domain was identified as a potential molecular marker of ART; resistance in vivo (DPC>5 h) and in vitro (RSA). Various antimalarial; drugs such as meflouine and piperaquine have been used as partner drugs; in ACTs. However, parasites resistant to these partner drugs have also; been reported, which may explain the reported slow parasite clearance; after ACT treatment. The success of ACTs in treating malaria infections; has generated optimism and proposals for malaria eradication by mass; drug administration (MDA), and successes have been achieved from several; studies. However, the impact of MDA on malaria transmission in the long; term, especially in low- and moderate-transmission settings, and the; potential consequences of developing drug resistance, requires careful; evaluation. There are a large number of studies and publications on; these related subjects, and it is impossible to include or cite all the; publications in this review. Additionally, some of the issues discussed; here are still being debated, requiring further investigation.国家自然科学基金; 国家外国专家局和教育部111计划; 美国国家过敏和传染病研究所项目资

The Role and Mechanism of Dihydroartemisinin in the Development of Non-Small Cell Lung Carcinoma

背景及目的 肺癌是最常见的恶性肿瘤，在全世界范围内，也是肿瘤导致死亡的首位原因。非小细胞肺癌是肺癌最常见的一种类型。非小细胞肺癌细胞对凋亡的抵抗性是抗肿瘤治疗的一大主要的障碍。因此，目前研究关注的热点是那些能提高治疗抵抗非小细胞肺癌细胞凋亡的新型复合物的发展。双氢青蒿素是一种重要的青蒿素衍生物，是从中草药植物青蒿素中提取出来的天然产物。作为一种非常有效的抗疟疾药物，双氢青蒿素（DHA）在全世界范围内已经是治疗抗疟原虫的一线治疗药。近期研究发现DHA对乳腺癌，乳头瘤病毒导致的宫颈癌，肝癌和胰腺癌有着良好的效果，此外，DHA对肺癌可以通过诱导凋亡达到抗肿瘤的作用，而没有明显的副作用。并且，电离辐...Abstract Background and Objective Lung cancer is the most common malignant tumor and the leading cause of cancer-relatedmortality worldwide. Non-small cell lung cancer (NSCLC) is the most common type of lungcancer. Resistance of NSCLC cells to apoptosis is a major obstacle in anticancer treatment. Accordingly,current researches focus on the development of innovative compounds that promotethe apo...学位：医学硕士院系专业：医学院_外科学学号：2452013115350

Transition-metal Lewis Acid Catalyzed Three-Component Asymmetric Mannich Reaction

不对称Mannich反应是高效构建碳碳键、碳氮键的重要反应之一，它在合成手性β-氨基羰基化合物、α-氨基酸、β-氨基酸、γ-氨基醇等一系列含氮化合物中有着广泛的应用，其产物β-氨基羰基化合物是合成许多生物活性药物和天然产物的重要中间体。 第一章为绪论部分。简要介绍了Mannich反应在抗疟疾药物、抗肿瘤药物、抗微生物试剂、消炎药物和抗痉挛药物合成方面的应用。Mannich侧链的存在可以增加药物分子的溶解性进而可以提高其生物利用度，而Mannich反应为分子中引入氨基烷基取代基提供了一种方便快捷的方法。此外，对金属催化不对称Mannich反应的研究现状进行了简述。 第二章将手性在金属铑Lew...Asymmetric Mannich reaction is one of the most powerful C-C/C-N bond-forming reactions for the construction of nitrogen-containing coupounds, such as β-amino carbonyl compounds, α-amino acids, β-amino acids, γ-amino alcohols. And the resulting optically enriched β-amino carbonyl compounds are valuable intermediates in the preparation of many drugs and natural products with useful biological proper...学位：理学硕士院系专业：公共卫生学院_转化医学学号：3262014115057

Comprehensive Chiral Spectroscopy of Compounds and its Application Research

学科交叉是当代科学发展的大趋势，处于学科交叉立交桥地位的手性科学，不仅在化学和医药领域不可或缺，而且在材料、环境和生命科学等领域也有重要应用。其中，手性光谱是进行手性立体化学研究的必备利器，近年来，采用集成的手性光谱[电子圆二色(ECD)、振动圆二色(VCD)、圆偏振发射(CPL)、手性拉曼(ROA)]技术确定手性化合物的绝对构型，已然成为一种主流方法。本文应用集成的ECD和VCD光谱技术，结合晶体结构分析和密度泛函理论(DFT)、含时密度泛函理论(TDDFT)计算，对手性聚集诱导发光(AIE)化合物和手性席夫碱金属络合物的手性立体化学结构、ECD和VCD光谱以及绝对构型关联进行了深入研究，探...Interdisciplinarity is the trend of modern scientific development. As the overpass in the cross-disciplines, chirality plays an important role not only in the fields of chemistry and medicine, but also in the materials, environment and life sciences. In recent years, using comprehensive chiral spectroscopy [electronic circular dichroism (ECD), vibrational circular dichroism (VCD), circularly polar...学位：理学博士院系专业：化学化工学院_无机化学学号：2052013015381

青蒿素的发现与诺贝尔生理学或医学奖

屠呦呦研究员因发现青蒿素这一杰出的贡献获得了2015年诺贝尔生理学或医学奖.青蒿素挽救了数百万人的生命,它的发现被认为是中国对全球人类健康所作出的最重要的贡献之一.先前集众多科学家参与和协作的“523项目“鲜为人知,诺贝尔奖颁给个人也因此引起了许多争议.本文概述了“523项目“的几个关键节点,并提出了我们的观点以帮助公美国国立卫生研究院过敏与传染病研究所的资

中西医结合现状及其发展前景*

China gradually established the guidelines for the integration of traditional Chinese and Western medicine since early 1960s. From then on, the combination of traditional Chinese medicine and Western medicine has made great progress in the field of disease diagnosis and treatment, the development of traditional Chinese medicine, the establishment of new medical system and medical personnel training and discipline construction. However, medical theory of the combination of traditional Chinese and Western medicine, personnel training system, and so on, still need to be further explored and improved. This paper reviewed current situation and developmental prospect of integrative Chinese and Western medicine, in order to promote development process of integrative Chinese and Western medicine.20世纪60年代初，中国逐步确立了中西医结合的卫生工作方针。从此，中西医结合医学在疾病诊疗、中医药开发、医学新体系建立以及医学人才培养与学科建设等方面都取得了长足的进步。然而，在中西医结合的医学理论和人才培养体系等方面仍亟待进一步探讨与完善。本文就中西医结合现状作一综述，旨在有助于促进中西医结合的发展进程。

Studies on Synthesis and Reaction Chemistry of the Specific Organohydridosilane Compounds

有机硅氢化合物是一类重要的氢化试剂，广泛应用于有机合成、金属有机合成和金属纳米粒子的制备。相对于传统的有机硅氢化合物（RnSiH4-n），新型功能性有机硅氢化合物的合成和应用正逐步成为该领域的研究热点和重点。本文着重于新型硅氢化合物的合成和反应性能研究，进行了如下五个方面的工作。 1.芳胺基氢基硅二醇化合物的合成和反应性能研究 以芳基伯胺（ArNH2）为原料，通过多步脱质子化以及盐消除反应合成了芳胺基氢基硅氯化合物Ar(R3Si)NSiHCl2；进一步以苯胺为缚酸剂，通过控制性水解反应制备了芳胺基氢基硅醇化合物Ar(R3Si)NSiH(OH)2(R=SiMe2Ph，SiMe3;Ar=2，6...Organohydridosilanes are one of the most important hydrogenation reagents widely utilized for syntheses of organic and organometallic compounds and metal nanoparticles. The traditionally used organohydridosilanes with formula of RnSiH4-n are now meeting with a limit in newly required synthesis because of its simplicity in function. Therefore, developing the new type of the organohydridosilanes wit...学位：理学博士院系专业：化学化工学院_物理化学学号：2052013015387

Drug Repurposing and Screening for New Compounds as New Strategies for Cancer Drug Development: Antitumor Activity of Praziquantel and Establishment of an Assay for Screening Spindle Checkpoint Inhibitors

研究旧有药物的抗肿瘤新用途是抗肿瘤药物研发的一个重要方向。很多获批上市药物被发现有抗肿瘤新用途，如沙利度胺，维生素C，非固醇类抗炎症药物。已有的研究表明抗寄生虫药物青蒿素及其衍生物具有很好的抗肿瘤活性，表明一些抗寄生虫药物有可能具有应用于肿瘤治疗的前景。吡喹酮是另外一种高效广谱的抗寄生虫药，已在临床上用于治疗疟疾多年，且毒性低，使用方便，目前还未见吡喹酮可能有抗肿瘤作用的相关报道。为了探讨吡喹酮是否有抗肿瘤的潜力，我们就吡喹酮对体外培养的人肿瘤细胞的杀伤能力进行了研究。我们的研究发现，尽管吡喹酮单独使用时对肿瘤细胞没有明显的细胞毒性，但是当它和化疗药物紫杉醇联合使用时能显著提高紫杉醇对肿瘤细胞...Exploiting new uses for old drugs has important implications for development of anti-cancer drugs. Some successful examples for this type of cancer drug development were previously reported such as thalidomide, vitamin C, NSAIDs (nonsteroidal anti-inflammatory drugs). It has been demonstrated that artemisinin, an antiparasitic agent, and its derivatives, had profound anti-tumor activity, providing...学位：理学博士院系专业：生命科学学院生物医学科学系_细胞生物学学号：3052009015418

中医现代化新论

中医学的传承和发展,核心是要实现中医现代化,关键是找到真正适合中医现代化的切入点。根源在于如何认识中医现代化的本质、中医现代化的必要性、实现中医现代化的方法以及中医现代化的意义。文章通过对以上4个层次的阐述,以及对其间沟通联系形成认识体系的解读,以期对中医学的发展有一定的启发意义。厦门市重大科技计划项目(No.3502Z20100006);;厦门市科技计划高校创新项目(No.3502Z20153027)~