苯并二氢吡喃腙衍生物的合成及其初步药理活性

为进一步筛选活性更强、副作用更小的抗绝经后骨质疏松症药物 ,在综合考察雷洛昔芬和异丙氧基异黄酮的基础上 ,设计合成一系列苯并二氢吡喃腙化合物 .化合物的结构均经波谱鉴定 ,并通过研究其对幼年小鼠子宫增重和血碱性磷酸酶活性的影响 ,初步考察化合物的药理活性 .结果表明 ,XY990 2具有较弱的雌激素受体激动作用和一定的雌激素受体拮抗作用 ,并有助于成骨细胞增殖 ,对治疗骨质疏松症是有利的 .     

丹参酮提取物物理化学质量属性相关性分析

目的：探寻丹参酮提取物化学成分的含量与物理性质之间的相关性。方法：HPLC测定50批丹参酮提取物中隐丹参酮、丹参酮IIA的含量,经典方法测定物理性质,将成分含量与物理性质进行相关性分析。结果：两变量组组内的隐丹参酮与丹参酮IIA含量,D10、D50、D90 之间,松装密度与振实密度,豪斯纳比率与压缩度指数均具有较强的相关性,休止角与均齐度、豪斯纳比率、压缩度指数具有一定的相关性,但相关性不强。两变量组的原始变量组间相关性系数最大不超过0.400,相关性不强。经过典型相关分析,3对典型变量的相关性显著,相关系数分别为0.851,0.674,0.565。结论：对于丹参酮提取物的化学、物理质量属性,原始变量组内具有较好的相关性,但组间相关性较差。相比原始变量,典型变量呈现出了较好的组间相关性,表明丹参酮提取物的物理化学属性之间具有一定的相关性。     

Network pharmacology explores the mechanisms of Eucommia ulmoides cortex against postmenopausal osteoporosis

Postmenopausal osteoporosis (PMOP) has become one of most frequent chronic disease worldwide with aging population. Eucommia ulmoides cortex (EU), a traditional Chinese medicine, has long since been used to treat PMOP. The aim of this study is to explore pharmacological mechanisms of EU against PMOP through using network pharmacology approach.The active ingredients of EU were obtained from Traditional Chinese Medicine System Pharmacology database, and target fishing was performed on these ingredients in UniProt database for identification of their relative targets. Then, we screened the targets of PMOP using GeneCards database and DisGeNET database. The overlapping genes between PMOP and EU were obtained to performed protein–protein interaction, Gene Ontology analysis, Kyoto encyclopedia of genes, and genomes analysis.Twenty-eight active ingredients were identified in EU, and corresponded to 207 targets. Also, 292 targets were closely associated with PMOP, and 50 of them matched with the targets of EU were considered as therapeutically relevant. Gene ontology enrichment analysis suggested that EU exerted anti-PMOP effects via modulating multiple biological processes including cell proliferation, angiogenesis, and inflammatory response. Kyoto encyclopedia of genes and genomes enrichment analysis revealed several pathways, such as PI3K-AKT pathway, mitogen-activated protein kinase pathway, hypoxia-inducible factors-1 pathway, tumor necrosis factor pathway, and interleukin-17 pathway that might be involved in regulating the above biological processes.Through the method of network pharmacology, we systematically investigated the mechanisms of EU against PMOP. The multi-targets and multi-pathways identified here could provide new insights for further determination of more exact mechanisms of EU.     

羟氯喹致眼毒性的文献分析

摘 要 目的：探讨羟氯喹致眼毒性的发生规律和特点，以期为临床安全用药提供参考。方法：检索截止2018年7月国内外文献数据库关于羟氯喹致眼毒性的临床研究文献，通过文献筛选后，对纳入的文献进行数据的提取和分析，包括患者性别、年龄、人种、原患疾病、累积剂量、给药剂量、治疗后不良反应出现时间、眼毒性类型、转归、严重程度、合并用药及眼科病史等。 结果：共检索到17篇文献20例患者，其中女19例，男1例；60岁以下患者占70%；白种人居多；原发疾病为系统性红斑狼疮10例，类风湿关节炎5例和其他疾病5例。眼毒性类型以黄斑变性、视力下降和视网膜病变居多。12例患者在治疗5年后出现药品不良反应（ADR）；累积剂量低于1 000 g与超过1 000 g出现眼毒性的患者数各占一半；羟氯喹日剂量超过6.5 mg·kg·d-1的患者比例较高。20例患者中有3例症状持续无法缓解。严重不良反应患者3例（15%），其余为一般不良反应。结论：羟氯喹致眼毒性较为罕见，但可能出现严重的不可逆损害。白种人、女性、60岁以下、患有系统性红斑狼疮或类风湿关节炎、治疗时间超过5年、每日给药剂量超过6.5 mg·kg-1·d-1的患者可能较易出现眼毒性，临床需格外关注，使用前和用药期间应定期行眼科检查。     

阿奇霉素对COPD急性发作期患者组蛋白去乙酰化酶2表达影响

目的 探讨慢性阻塞性肺疾病(COPD)患者在急性发作期血液中白介素-8(IL-8)、肿瘤坏死因子(TNF-α)以及组蛋白去乙酰化酶2(HDAC2)表达.观察阿奇霉素、地塞米松等药物体外干预对COPD急性发作期(AECOPD)血液中炎症因子以及HDAC2表达影响.方法 COPD稳定期患者13例为对照组,抽取空腹静脉血5 ...     

Exosomes Derived from Glioma Cells under Hypoxia Promote Angiogenesis through Up-regulated Exosomal Connexin 43

Glioblastoma multiform (GBM) is a highly aggressive primary brain tumor. Exosomes derived from glioma cells under a hypoxic microenvironment play an important role in tumor biology including metastasis, angiogenesis and chemoresistance. However, the underlying mechanisms remain to be elucidated. In this study, we aimed to explore the role of connexin 43 on exosomal uptake and angiogenesis in glioma under hypoxia. U251 cells were exposed to 3% oxygen to achieve hypoxia, and the expression levels of HIF-1α and Cx43, involved in the colony formation and proliferation of cells were assessed. Exosomes were isolated by differential velocity centrifugation from U251 cells under normoxia and hypoxia (Nor-Exos and Hypo-Exos), respectively. Immunofluorescence staining, along with assays for CCK-8, tube formation and wound healing along with a transwell assay were conducted to profile exosomal uptake, proliferation, tube formation, migration and invasion of HUVECs, respectively. Our results revealed that Hypoxia significantly up-regulated the expression of HIF-1α in U251 cells as well as promoting proliferation and colony number. Hypoxia also increased the level of Cx43 in U251 cells and in the exosomes secreted. The uptake of Dio-stained Hypo-Exos by HUVECs was greater than that of Nor-Exos, and inhibition of Cx43 by ^37,43gap27 or lenti-Cx43-shRNA efficiently prevented the uptake of Hypo-Exos by recipient endothelial cells. In addition, the proliferation and total loops of HUVECs were remarkably increased at 24 h, 48 h, and 10 h after Hypo-Exos, respectively. Notably, ^37,43gap27, a specific Cx-mimetic peptide blocker of Cx37 and Cx43, efficiently alleviated Hypo-Exos-induced proliferation and tube formation by HUVECs. Finally, ^37,43gap27 also significantly attenuated Hypo-Exos-induced migration and invasion of HUVECs. These findings demonstrate that exosomal Cx43 contributes to glioma angiogenesis mediated by Hypo-Exos, and suggests that exosomal Cx43 might serve as a potential therapeutic target for glioblastoma.     

The upregulated intestinal folate transporters direct the uptake of ligand-modified nanoparticles for enhanced oral insulin delivery

Transporters are traditionally considered to transport small molecules rather than large-sized nanoparticles due to their small pores. In this study, we demonstrate that the upregulated intestinal transporter (PCFT), which reaches a maximum of 12.3-fold expression in the intestinal epithelial cells of diabetic rats, mediates the uptake of the folic acid-grafted nanoparticles (FNP). Specifically, the upregulated PCFT could exert its function to mediate the endocytosis of FNP and efficiently stimulate the traverse of FNP across enterocytes by the lysosome-evading pathway, Golgi-targeting pathway and basolateral exocytosis, featuring a high oral insulin bioavailability of 14.4% in the diabetic rats. Conversely, in cells with relatively low PCFT expression, the positive surface charge contributes to the cellular uptake of FNP, and FNP are mainly degraded in the lysosomes. Overall, we emphasize that the upregulated intestinal transporters could direct the uptake of ligand-modified nanoparticles by mediating the endocytosis and intracellular trafficking of ligand-modified nanoparticles via the transporter-mediated pathway. This study may also theoretically provide insightful guidelines for the rational design of transporter-targeted nanoparticles to achieve efficient drug delivery in diverse diseases.     

腹腔镜监视下Ⅰ期经肛门巨结肠根治术10例报告

1998年,Torre首先提出治疗先天性巨结肠采用一期经肛门拖出术（transanal endorectal pull-through or transanal surgvry,TAS）。手术经肛门施行．不需开腹或应用腹腔镜技术游离肠管。该术式具有简便、合并症少、费用低、创伤小等优点。在国内尤其是经济欠发达或没有腹腔镜技术的地区得到迅速开展,然而该术式视野仅限于肛门区．术中腹腔内情况难以发现。如结肠系膜出血、结肠扭转、拖下吻合的结肠张力过大、腹腔内脏器（大网膜、小肠、卵巢）嵌入肌鞘内等。基于此我们采用微型腹腔镜监视下完成该手术。取得良好的效果．现报告如下。     

Does Waldenstrom’s macroglobulinemia also cause bone destruction? A rare case report

Waldenstrom’s macroglobulinemia (WM) is a rare type of malignant B-cell lymphoma. The main feature of WM is elevated serum monoclonal immunoglobulin M, similar to multiple myeloma (MM). Unlike in MM, the rarity of destructive bone lesions in WM has been repeatedly emphasized. We report a unique case of WM with a vertebral compression fracture as the first symptom. This case highlights that the presence or absence of bone destruction may not clearly distinguish between WM and MM. The possibility of WM should be considered in patients with vertebral fracture and destruction as the first presentation. Performing vertebral bone marrow aspiration biopsy during percutaneous vertebroplasty is a convenient and effective method to assist in the diagnosis of WM.     

Highlight from recent cancer literature

正Two cellular lineages are identified to initiate prostate cancer Identifying the cells of origin for prostate cancer is a key step to improve disease prevention and therapeutics. However, the identity of these cells has been long debated and remains inadequately defined because of a lack of proper animal models. Now, recent findings by Xin and colleagues provide new insight on the origins of prostate cancer. Their report, published in Cancer Cell, shows that prostate cancer can initiate from