基于SD-OCT建立新的前膜分级法评估IMEM对年龄相关性白内障患者术后视功能的影响

目的：在单纯白内障术前,根据频域光学相干断层扫描技术(SD-OCT)显示年龄相关性白内障合并特发性黄斑前膜(IMEM)的患眼黄斑中心凹内部精细结构的紊乱程度建立新的IMEM分级法,评估其用于预测年龄相关性白内障患者的视功能预后的价值。

方法：选取2017-10/2018-11在暨南大学附属深圳市眼科医院因年龄相关性白内障单纯行超声乳化白内障摘除联合人工晶状体植入术,术前眼底检查发现合并IMEM者64例80眼,根据SD-OCT显示的IMEM对黄斑中心凹内部精细结构的破坏程度将IMEM分为4级。对合并各级IMEM的患者术前、术后3mo的最佳矫正视力(BCVA,LogMAR)、平均视敏度(MS)、黄斑中心凹厚度(CMT)、黄斑前膜进展率进行对比分析。

结果：在SD-OCT图像上,随着合并的IMEM分级的增高,前膜越明显,患者的黄斑中心凹凹部丢失和内部结构紊乱越严重。白内障术前及术后3mo的患眼BCVA随着所合并的IMEM分级升高而增加(F=37.72、26.43,均P<0.001)。白内障术前及术后3mo的患眼MS随着所合并的IMEM分级升高而降低(F=43.77、28.96,均P<0.001)。术后3mo CMT的改变和黄斑前膜进展率并不一致,合并各级IMEM的患眼CMT与术前均无差异(P>0.05),但黄斑前膜进展率呈显著上升趋势(χ²_趋势=12.59,P<0.001)。

结论：借助于SD-OCT对年龄相关性白内障合并的IMEM进行新的精细分级,可以更精准地预测该类患者单纯行白内障手术术后的视功能恢复情况。     

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。     

髋关节置换患者不同阶段深静脉血栓风险调查及影响因素分析

目的：分析髋关节置换的患者不同阶段深静脉血栓（deep venous thrombosis,DVT）风险的变化情况及影响因素。方法：采用方便抽样法,使用一般资料调查表、Autar DVT风险量表、日常生活能力量表（Barthel量表）和Charlson合并症指数分别于入院当天、手术当天、出院当天、出院1个月对重庆市某三级甲等医院209名髋关节置换的患者进行追踪性观察。结果：各阶段DVT风险评估总分为12.31~15.42分,自入院当天开始上升,在手术当天达到最高值后,呈下降趋势,但出院当天DVT的风险高于入院当天。多元线性回归分析显示,入院时最有效的血栓预测指标为日常生活能力（β=-0.460,P＜0.05）,疾病类型是入院时DVT风险的独立影响因素（β=0.194,P=0.000）;体质指数（body mass index,BMI）在手术后至出院1个月均为血栓风险的重要指标（β=0.315,β=0.302,β=0.251,均P＜0.05）;年龄、住院次数和Charlson合并症是入院至出院1个月预测DVT的重要指标（β=0.229,β=0.098,β=0.258;β=0.383,β=0.133,β=0.423;β=0.273,β=0.114,β=0.115,β=0.313;β=0.217,β=0.115,β=0.223,均P＜0.05）,术后开始下床时间也是DVT的影响因素（β=0.258,β=0.278,均P＜0.05）。结论：髋关节置换患者从入院至出院1个月,DVT风险均处于中高危水平。高龄、肥胖、Charlson合并症、多次住院史、术后开始下床时间晚是DVT的危险因素。应根据不同阶段的危险因素采取针对性预防措施,提示医务人员对于出院时DVT高危患者给予持续关注,重视全面系统的院外血栓预防措施的普及,加强出院后的随访。     

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.     

右冠状动脉介入治疗的临床疗效及安全性观察

目的　观察右冠状动脉 (冠脉 )介入治疗 (PCI)的临床疗效及安全性。方法　回顾性分析 1995— 2 0 0 2年间进行的 188例 2 0 2处右冠脉靶血管介入治疗的特点。结果　 188例右冠脉病变共 2 0 2处右冠脉靶血管 ,靶血管介入成功率为 91 1%,其中 15 0例植入支架 174枚 ;PCI失败 18例 ,均发生在右冠脉近中段 ;室颤 2例 ,PCI后无复流现象 6例 ,早期急性冠脉闭塞 1例 ,冠脉破裂 3例 ,死亡 3例。随访 1～ 96月 ,绝大多数临床症状改善。结论　右冠脉病变的PCI是一项成功率高、并发症少、近远期临床疗效俱佳的治疗手段。