煤矿区大气污染与儿童呼吸道疾病住院人数的时间序列分析

目的评价神木县大气污染与儿童呼吸道感染住院人数的关系。方法收集2009年11月至2012年10月间神木县的气象因素（气温、相对湿度）和环境因素：二氧化硫（SO,）、二氧化氮（NO：）和可吸入颗粒物（PM10）,以及16岁及以下儿童的住院资料。利用SAS9．3对气象、环境因素和住院人数资料进行描述性分析,并判断主要污染物。利用R3．0．1统计软件的建立Poisson回归的广义相加模型,引入大气污染物浓度及气象因素拟合线性模型,并考虑其滞后效应,评价主要大气污染物对儿童呼吸道感染住院的相对危险度。结果神木县的首要污染物为PM10,PM10与空气污染指数（API）的相关系数为0．917,P〈0．01。在控制了长期趋势、“星期几效应”、气象因素及其它污染物的影响后发现,首要大气污染物PM10浓度每上升10μg／m3时,每日呼吸道感染住院患儿的上呼吸道相对危险度（RR）及其95％可信区间（95％cx）为1．002（0．996～1．007）,t=0．589,P=0．556;下呼吸道为1．000（0．995～1．005）,t=-0．007,P=0．995。当日或滞后1～10日内PM10浓度变化均不能显著改变儿童上、下呼吸道感染的住院率。结论神木县首要污染物PM10浓度变化对儿童上、下呼吸道感染的住院情况无明显影响。     

A newly synthesized platinum-based compound (PBC-II) increases chemosensitivity of HeLa ovarian cancer cells via inhibition of autophagy

There are many mechanisms of resistance, chemoresistance of HeLa cells to anti-cancer agents seems to be autophagy-mediated. While using very effective anti-cancers such as Doxorubicin and cisplatin, cells overcome the cytotoxicity of these drugs through promotion of what so-called cytoprotective autophagy. Here in this study, we sought to introduce a novel platinum-based compound PBC-II that possesses anti-cancer activity. Our data showed that PBC-II is able to induce apoptosis at relatively low concentrations, with no detectable reactive oxygen species (ROS). However, further experiments demonstrated that exposure of HeLa cells to PBC-II did not promote autophagy; rather, it resulted in accumulation of p62 and decrease in LC3-II levels. Autophagy was then promoted in HeLa cells pharmacologically by Doxorubicin and genetically by siRNA IL-10. In order to confirm promotion of autophagy in our model, we performed acridine orange staining to assess for autophagy under microscope as well as via flow cytometry. We then measured protein level of autophagy markers p62 and LC3 by western blot. Our data indicated that PBC-II interferes with therapy-induced autophagy. We also determined PI3K activity while co-incubation of PBC-II with autophagy inducers. It was clear that PI3K activation decreased when PBC-II was co-administered with autophagy inducers. Collectively, PBC-II exerts unique anti-proliferative effects associated with inhibition of autophagy, which indicates that PBC-II is potentially a promising agent to be used in resistant ovarian tumors.     

10-乙酰乙酰紫杉醇标准品的制备工艺研究

目的 研究半合成紫杉醇中工艺杂质10-乙酰乙酰紫杉醇的制备方法。方法 选择性地保护紫杉醇的2''位和7位羟基,然后在碱性条件下脱去10位乙酰基,未保护的10位羟基与2,2,6-三甲基-4H-1,3-二噁英-4-酮进行缩合,最后脱去7位和2''位的保护基,制备得到10-乙酰乙酰紫杉醇。结果 以紫杉醇为原料通过5步反应制备得到10-乙酰乙酰紫杉醇,总收率为27%,纯度高达95%。结论 为10-乙酰乙酰紫杉醇标准品的制备提供了简便易行的方法,有利于紫杉醇原料药的质量控制与评价。     

3,5-Dimethoxy-4-hydroxy myricanol ameliorates photoreceptor cell degeneration in Pde6brd10 mouse model

Introduction: Retinitis pigmentosa (RP) caused by the photoreceptor cell degeneration is currently incurable and leads to partial or complete blindness eventually. 3,5-dimethoxy-4-hydroxy myricanol (DM) is a novel compound isolated from the leaves of Micromelum integerrimum, with proliferative activities on NIH3T3 cells. This study was to investigate whether DM could mitigate retinal degeneration of rd10 mice, a well-characterized mouse model of RP. Materials and method: Rd10 mice were treated with DM daily by intraperitoneal injection from postnatal day 12 (P12) to P26. Electroretinography (ERG) reflects the mass response of photoreceptor cells and was used to test the outer retinal function after DM treatment. Haematoxylin and Eosin staining was used to show the retinal morphology and evaluate the rod photoreceptor cell loss. TUNEL assay was used to detect the apoptosis-positive cells. Inflammatory factors were measured by ELISA to show the inflammatory response. Real-time PCR and western blot were applied to measure the gene and protein change to explore the underlying mechanisms. Results: Results showed that DM significantly improved the retinal function by increasing the ERG amplitude, preserving the retinal morphology, reducing photoreceptor cell apoptosis, decreasing inflammatory response, and inhibiting endoplasmic reticulum stress in rd10 mice. Conclusion: This is the first time when the protective effects of DM against photoreceptor cell degeneration of rd10 mice have been demonstrated, providing scientific rationale to develop DM as a potential agent to treat RP.     

低聚原花青素对葡聚糖硫酸钠诱导小鼠溃疡性结肠炎的保护作用

 目的 研究低聚原花青素(oligomeric proanthocyanidins,OPC)对葡聚糖硫酸钠(dextran sulfate sodium,DSS)诱导的溃疡性结肠炎(ulcerative colitis,UC)小鼠的治疗作用,并初步探讨其保护机制。方法 选取雄性C57小鼠40只,选取8只为正常对照组。其他32只用2.5%的DSS进行UC造模后,随机分为模型组、美沙拉嗪组(美沙拉嗪500 mg/kg)、低剂量组(OPC500 mg/kg)、高剂量组(OPC1000 mg/kg),每组8只。连续给药7 d后处死小鼠,评估疾病活动指数(DAI),观察结肠病理变化,评估结肠大体形态损伤指数(colon macroscopic damage index,CMDI),计算检测血清IL-10水平,测定髓过氧化物酶(myeloperoxidase,MPO)活性。结果 与正常对照组相比,造模后各组小鼠的DAI评分明显升高,结肠黏膜变薄、上皮脱落和炎性细胞浸润,CMDI评分明显升高,结肠长度和血清IL-10水平明显降低,组织MPO活性明显升高,差异有统计学意义(P<0.05);与模型组相比,美沙拉嗪组、低剂量组和高剂量组的DAI评分和CMDI评分显著降低,结肠长度延长,血清IL-10水平明显升高,MPO活性明显降低,差异有统计学意义(P<0.05)。且美沙拉嗪组与高剂量组接近,均优于低剂量组。结论 OPC可通过减少氧化应激,抑制炎性反应,降低DSS诱导UC小鼠的DAI,改善小鼠结肠组织病理形态,具有治疗作用。