Sox2 enhances the tumorigenicity and chemoresistance of cancer stem-like cells derived from gastric cancer

Gastric cancer stem-like cells(GCSCs) have been identified to possess the ability of self-renewal and tumor initi-ation.However,the mechanisms involved remain largely unknown.Here,we isolated and characterized the GCSCs by side population(SP) sorting procedure and cultured sphere cells(SC) from human gastric cancer cell lines SGC-7901,BGC-823,MGC-803,HGC-27 and MKN-28.The sorting and culture assay revealed that SP cells proliferated in an asymmetric division manner.In addition,SP cells exhibited a higher potential of spheroid colony formation and greater drug resistance than non-SP cells(NSP).Moreover,the SC were found with enhanced capabilities of drug resistance in vitro and tumorigenicity in vivo.Sox2 mRNA and protein was highly and significantly overex-pressed in the SP cells and SC.Importantly,downregulation of Sox2 with siRNA obviously reduced spheroid colony formation and doxorubicin efflux,as well as increased apoptosis rate in sphere cells in vitro and suppressed tumori-genicity in vivo.These results suggest that both SP cells and cultured SC enrich with GCSCs and that Sox2 plays a pivotal role in sustaining stem cell properties and might be a potential target for gastric cancer therapy.     

武汉市中学生初次吸烟行为与生活事件的关系初探

目的 分析武汉市中学生初次吸烟行为与日常生活事件的关系以及压力对青少年初次吸烟的影响。方法 采用分层整群随机抽样法,对武汉市城区和郊区22所学校的6994名在校初中生进行问卷调查,选择报告过去一年内开始吸烟和从未吸过烟的学生共5536人作为本次分析对象。结果 武汉市中学生在调查的前一年内开始吸整支烟的吸烟率为8.2％,男生高于女生,初二学生高于初一学生,初三学生略有下降。控制性别、年龄、城乡和年级的影响,多因素logistic回归分析结果显示,武汉市青少年初次吸烟行为与家庭、学校的负性生活事件呈正性相关(P<0.05),而与学校方面的正性生活事件呈负性相关(P<0.05)。结论 青少年学生初次吸烟行为与应激性生活事件有密切的联系,特别是学校和家庭方面的生活事件。     

Paracrine rather than autocrine regulation of myeloma-cell growth and differentiation by interleukin-6

To explore the mechanisms involved in the pathogenesis of human multiple myeloma (MM), we investigated the potential role of interleukin-6 (IL-6), a B-cell differentiation factor in humans, and a growth factor for rat/mouse heterohybridomas and murine plasmacytomas. Using a heterohybridoma assay, we found that two well-documented human myeloma cell lines, RPMI 8226 and U266, did not secrete IL-6 and did not express RNA messengers for IL-6. Neutralizing antibodies to IL-6 did not inhibit their proliferation, and recombinant IL-6 did not stimulate it. Taken together, these data show that IL-6 is not the autocrine growth factor of these human myeloma cell lines. A high production of IL-6 was found in the bone marrows of patients with fulminating MM, compared with patients with inactive or slightly active MM, or to healthy donors. This IL-6 production was assigned to adherent cells of the bone-marrow environment but not to myeloma cells. A spontaneous proliferation of myeloma cells freshly isolated from patients was observed in short-term cultures. Recombinant IL-6 was able to amplify it two- to threefold. The spontaneous proliferation of the myeloma cells was inhibited by anti-IL-6 antibodies and reinduced by recombinant IL-6. After 2 to 3 weeks of culture, the myeloma-cell proliferation progressively declined and no IL-6-dependent myeloma cell lines could be obtained despite repeated additions of fresh IL-6 and costimulation with other cytokines such as tumor necrosis factor (TNF)beta, or IL-1 beta. These data demonstrated a paracrine but not autocrine regulation of the growth and differentiation of myeloma cells by IL-6.     

Cyclosporine A stimulated hair growth from mouse vibrissae follicles in an organ culture model

Hypertrichosis is one of the most common side effects of systemic cyclosporine A therapy.It has been previously shown that cyclosporine A induces anagen and inhibits catagen development in mice.In the present study,to explore the mechanisms of cyclosporine A,we investigated the effects of cyclosporine A on hair shaft elongation,hair follicle cell proliferation,apoptosis,and mRNA expression of selected growth factors using an organ culture model of mouse vibrissae.In this model,cyclosporine A stimulated hair growth of normal mouse vibrissae follicles by inhibiting catagen-like development and promoting matrix cell proliferation.In addition,cyclosporine A caused an increase in the expression of vascular endothelial growth factor(VEGF),hepatocyte growth factor(HGF),and nerve growth factor(NGF),and inhibited follistatin expression.Our findings provide an explanation for the clinically observed effects of cyclosporine A on hair growth.The mouse vibrissae organ culture offers an attractive model for identifying factors involved in the modulation of hair growth.     

格列吡嗪片体外溶出度的比较

目的：对３种市售格列吡嗪片的体外溶出度进行比较,为其质量控制提供参考,方法：选用转篮法,并对Ｔ５０,Ｔｄ等参数进行统计分析,结果：３种格列吡嗪片在２０ｍｉｎ的溶出量均超过标示量的８０％,但配对ｔ检验显示Ｔ５０,Ｔｄ具有显著差异（Ｐ〈０．０１）。结论：Ｉｔａ厂的格列吡嗪片其体溶出较ＨＮ厂和ＳＨ厂的产品为优。     

双波长紫外分光光度法测定盐酸普鲁卡因溶液的含量

目的：为准确测定盐酸普鲁卡因溶液的含量。方法;采用双波长分光光度法测定盐酸普鲁卡因溶液的含量,测定波长为２８９ｎｍ,参比波长为２５９．７ｎｍ。结果;平均回收率为１００．７％,ＲＳＤ＝１．０６％。结论：本方法能有效地消除盐酸普鲁卡因分解产物对氨基苯甲酸的干扰,准确测得其真实含量。     

Monte Carlo modeling of a high-sensitivity MOSFET dosimeter for low- and medium-energy photon sources

Metal-oxide-semiconductor field effect transistor (MOSFET) dosimeters are increasingly utilized in radiation therapy and diagnostic radiology. While it is difficult to characterize the dosimeter responses for monoenergetic sources by experiments, this paper reports a detailed Monte Carlo simulation model of the High-Sensitivity MOSFET dosimeter using Monte Carlo N-Particle (MCNP) 4C. A dose estimator method was used to calculate the dose in the extremely thin sensitive volume. Efforts were made to validate the MCNP model using three experiments: (1) comparison of the simulated dose with the measurement of a Cs-137 source, (2) comparison of the simulated dose with analytical values, and (3) comparison of the simulated energy dependence with theoretical values. Our simulation results show that the MOSFET dosimeter has a maximum response at about 40 keV of photon energy. The energy dependence curve is also found to agree with the predicted value from theory within statistical uncertainties. The angular dependence study shows that the MOSFET dosimeter has a higher response (about 8%) when photons come from the epoxy side, compared with the kapton side for the Cs-137 source.     

柔性纳米脂质体双氯芬酸钠外用透皮吸收的效果

目的:观察双氯芬酸钠柔性纳米脂质体皮肤给药缓释系统体外透皮吸收情况。方法:验于2005-03/11在中南大学湘雅医院中西结合研究所完成。实验材料:双氯芬酸钠柔性纳米脂质体(中南大学化工研究所,将双氯芬酸钠制成纳米粒,并包封于卵磷脂及其有生物膜特性和功能的脂质体中,其粒径为30～100nm),扶他林(双氯芬酸钠)。实验分组:15只健康的SD大鼠按随机数字表法分为3组:质量分数为0.01的扶他林组、质量分数为0.05的外用双氯芬酸钠柔性纳米脂质体组和质量分数为0.1的外用双氯芬酸钠柔性纳米脂质体组,每组5只。将鼠皮装于Franz扩散池,角质层面向供给室,真皮层面向接受池,分别将质量分数为0.05的外用双氯芬酸钠柔性纳米脂质体25mg、质量分数为0.1的外用双氯芬酸钠柔性纳米脂质体12.5mg和质量分数为0.01的扶他林125mg(含双氯芬酸钠均为1.25mg)均匀涂布于大鼠皮肤角质层表面,分别于2,4,6,8,10,12h于接受池取样5mL,用0.45μm微孔滤膜过滤。滤液用生理盐水稀释至10mL,于276nm处测定吸光度值,扣除生理盐水的吸光度值后代入标准曲线,计算累积透过量和12h累积透过率,对比3种制剂经大鼠皮肤的体外透皮吸收差异。结果:质量分数为0.05,0.1的外用双氯芬酸钠柔性纳米脂质体组累积透过量、12h累积透过率均高于质量分数为0.01的扶他林组[12h累积透过率分别为(70.76±0.23)%,(75.2±0.32)%,(33.51±0.29)%],差异有显著性意义(t=317.17,232.54,P<0.01);质量分数为0.05的外用双氯芬酸钠柔性纳米脂质体组与质量分数为0.1的外用双氯芬酸钠柔性纳米脂质体组累积透过量、12h累积透过率差异无显著性意义(P>0.05)。结论:双氯芬酸钠柔性纳米脂质体能有效渗透皮肤组织。     

激光多普勒血流仪测定兔后肢电损伤局部血流变化

目的:应用激光多谱勒血流仪监测局部血流变化以判断高压电损伤程度。方法:实验于2003-10/2005-01在深圳市第二人民医院烧伤整形科实验室完成。选择健康新西兰兔32只,采用自制电击设备建立电损伤重度损伤模型,将电击区域均分为A,B,C,D,E5个区,依次为肢体远端到近端。在A,B,E区于伤前、伤后0,2,4,24,48,72h,4,5,6,7d测定局部皮肤表面及肌肉中血流值变化情况。结果:①损伤前A、B、E区皮肤表面平均血流值分别为75.74,78.86,84.21PU,表明肢体近端至远端血流值逐渐减少,各点之间血流值差异无显著性意义(P>0.05)。②A区皮肤表面伤后2h血流值明显低于伤后0,4,24,48h,差异有显著性意义[分别为(27.22±22.80),(91.60±74.37),(63.97±44.41),(58.80±52.50),(58.72±39.02)PU,t=2.357,2.856,2.364,2.998,P<0.05],此时组织学表现为细胞水肿明显,有少量中性粒细胞浸润。A区皮肤表面伤后4h血流值增加,但至伤后4d才逐渐恢复到伤前水平。A区肌肉伤后2h血流值低于伤后24h,4d,差异有显著性意义[分别为(83.70±73.30),(135.10±63.07),(160.26±71.32)PU,t=2.383,2.367,P<0.05]。此时组织学表现为肌纤维肿胀,部分横纹消失,肌纤维的胞浆呈红染的疏松水波状和网状结构。③B区皮肤表面伤后4,24h血流值低于损伤前和伤后0h,差异有显著性意义[分别为(50.75±41.69),(47.23±35.36),(78.86±26.47),(83.89±32.77)PU;t=2.324,2.732,2.826,3.189,P<0.05,0.01],组织学表现同A区。B区局部肌肉伤后4h血流值低于伤后0,48,72h,差异有显著性意义[分别为(64.65±34.08),(107.11±36.50),(130.30±75.04),(180.56±72.59)PU,t=2.545,2.712,2.963,P<0.05]。此时组织学表现基本上同A区伤后2h。④E区皮肤表面各时相点之间血流值差异无显著性意义(P>0.05)。组织学表现同A区。E区局部肌肉伤后2h血流值低于伤后0,24,72h,差异有显著性意义[分别为(129.11±65.08),(175.02±71.67),(169.14±71.05),(196.64±67.34)PU,t=2.776,2.521,2.895,P<0.05]。此时组织学表现为肌纤维溶解断裂及中性粒细胞浸润。结论:用激光多谱勒血流仪监测损伤局部血流变化可以判断高压电损伤程度。