核糖核酸干扰沉默生长抑制因子1基因表达对胃腺癌AGS细胞凋亡的影响

目的 探讨RNA干扰沉默生长抑制因子1(ING1)基因表达对胃腺癌AGS细胞凋亡的影响。方法人胃腺癌细胞株AGS经常规培养后分为空白对照组、阴性对照组[转染阴性对照小干扰RNA(siRNA)序列]、siRNA组（转染特异性ING1 siRNA序列）。应用免疫荧光、定量PCR和免疫印迹方法检测转染后不同时间的ING1基因表达沉默效果。应用流式细胞技术检测ING1基因表达沉默对AGS细胞凋亡的影响。结果ING1主要在AGS细胞胞质中表达。在荧光定量PCR技术检测中将空白对照组的ING1基因表达量设为1,则转染后24和40 h阴性对照组的ING1基因相对表达量分别为0.88±0.16和0.92±0.13,siRNA组ING1基因相对表达量分别为0.38±0.09和0.17±0.06。空白对照组和阴性对照组比较,P值分别=0.78和0.82。空白对照组和siRNA组比较,P值均=0.01。阴性对照组和siRNA组比较,P值分别=0.02和0.01。免疫印迹技术检测结果显示,转染后40 h AGS细胞中ING1蛋白表达水平明显下调。空白对照组AGS细胞凋亡率为11.06％±0.97％,阴性对照组、siRNA组转染40 h后AGS细胞凋亡率为11.82％±0.69％和 6.70％±0.41％。空白对照组与siRNA组比较P=0.024。空白对照组与阴性对照组比较P=0.76。阴性对照组与siRNA组比较P=0.019。结论ING1在人胃癌细胞凋亡过程中发挥重要作用,可能成为胃癌基因治疗的新靶点。     

生长因子受体结合蛋白2在人类真核翻译延长因子1A2促进胰腺癌发生发展中的作用

目的 明确生长因子受体结合蛋白2(GRB2)在人类真核翻译延长因子1A2(EEFlA2)促进胰腺癌发生发展中的作用.方法 用腺病毒质粒Ad5/F35-EEFl A2转染胰腺癌细胞株SW1990(EEFlA2低表达),应用小干扰RNA(siRNA)技术下调胰腺癌细胞BxPC-3 (EEF1A2高表达)中EEFlA2的表达水平,用RT-PCR及Western印迹方法检测SW1990和BxPC-3细胞株处理前后GRB2的表达.化学合成GRB2特异高效的siRNA干扰片段,干预胰腺癌细胞BxPC-3后通过MTT和Transwell实验观察BxPC-3细胞增殖和运动能力的变化.统计学处理采用单因素方差分析.结果 腺病毒Ad5/F35-EEF1A2转染人胰腺癌细胞株SW1990后,GRB2的mRNA和蛋白表达水平均明显升高(F=5.67和6.39,P均＜0.05).EEF1A2-siRNA抑制BxPC-3胰腺癌细胞EEF1A2表达后,GRB2的mRNA和蛋白表达水平均明显下调(F=-6.59和4.69,P均＜0.05).BxPC-3在被转染siRNA-GRB2后,MTT结果显示72 h时,siRNA-GRB2组吸光度值为1.22±0.14,与阴性对照组和空白对照组(1.42±0.15和1.39±0.15)相比,差异有统计学意义(F=6.63,P＜0.05).Transwell实验结果显示siRNA GRB2组细胞侵袭能力减弱,24 h后穿膜细胞数为(24.10±4.25)个,与阴性对照组[(54.72±5.24)个]及空白对照组[(51.26±6.23)个]相比,差异有统计学意义(F=55.00,P＜0.05).结论 GRB2是EEF1A2促进胰腺癌发生发展的关键分子.     

组蛋白去乙酰化酶1对人胰腺癌细胞增殖凋亡的影响

目的 观察沉默组蛋白去乙酰化酶1(HDAC1)基因对人胰腺癌PaTu8988细胞增殖及凋亡的影响.方法 培养胰腺癌PaTu8988细胞株,设空白对照组(未予任何处理)、阴性对照组[予30 nmol/L阴性小干扰RNA(siRNA)]、HDACI低剂量组(予15 nmol/L HDAC1 siRNA)和HDAC1高剂量组(予30 nmol/L HDAC1 siRNA),siRNA转染48 h后,分别采用相对实时定量PCR法和Western印迹法检测HDAC1基因在mRNA和蛋白水平的沉默效率,细胞计数试剂盒法检测siRNA干扰前、后细胞增殖变化,流式细胞技术检测干扰前、后细胞凋亡变化.结果 转染HDAC1siRNA 48 h后,低剂量组和高剂量组人胰腺癌PaTu8988细胞中HDAC1 mRNA表达率分别为46.1%±6.1%和32.3%±1.4%,均显著低于空白对照组(100.0%±3.4%)和阴性对照组(87.4%±28.3%),差异有统计学意义(P值均<0.05).空白对照组和阴性对照组HDAC1蛋白表达水平高于其余两组.空白对照组、阴性对照组、HDAC1低剂量组和HDAC1高低剂量组的细胞存活率分别为100.0%±17.1%、87.1%±5.0%、68.7%±4.7%和61.6%±2.0%,细胞凋亡率分别为4.20%±0.95%、4.59%±1.26%、10.09%±1.36%和11.19%±6.07%,空白对照组和阴性对照组与其余两组比较,差异均有统计学意义(P值均<0.05).结论 HDAC1 siRNA能特异、有效地抑制人胰腺癌PaTu8988细胞HDAC1表达,抑制细胞增殖、诱导细胞凋亡.     

干扰趋化因子Fractalkine的表达对胰腺癌细胞株生物学功能的影响

目的 探讨阻断趋化因子Fractalkine(FKN)对胰腺癌细胞株SW-1990和PNAC-1生物学功能的影响.方法 腺病毒作为载体包装FKN-小干扰RNA(siRNA),转染人胰腺癌细胞株SW-1990和PNAC-1.应用克隆形成实验、MTT法和细胞侵袭实验检测FKN-siRNA转染与否、胰腺癌细胞增殖和侵袭力的变化.Western印迹法和RT-PCR检测转染FKN-siRNA的胰腺癌细胞FKN、TNF-α和IL-6蛋白和mRNA的表达.统计学处理采用单因素方差分析.结果 FKN-siRNA转染人胰腺癌细胞株SW-1990和PNAC-1后,与对照组的克隆数[分别为(1.97％±0.25％)和(1.77％±0.25％)]和阴性FKN-siRNA组的克隆数[分别为(2.10％±0.30％)和(1.97％±0.25％)]相比,细胞克隆增大,克隆数[分别为(5.27％±0.35％)和(4.60％±0.30％)]增多,差异均有统计学意义(F=113.51、103.86,P值均＜0.05).MTT实验48 h和72 h后,转入FKN-siRNA的转染人胰腺癌细胞株SW-1990和PNAC-1吸光度(48 h时分别为1.28±0.07和1.19±0.14;72 h时分别为1.49±0.11和1.52±0.16)高于对照组([48 h时分别为0.80±0.03和0.74±0.11;72 h时分别为0.89±0.03和0.93±0.04)和阴性FKN-siRNA组(48 h时分别为0.85±0.02和0.76±0.05;72 h时分别为0.89±0.02和1.07±0.09),差异均有统计学意义(F=83.80、71.99、17.19、23.51,P值均＜0.05).细胞侵袭实验中,转入FKN-siRNA的细胞侵袭力强于对照组和阴性FKN-siRNA组,差异有统计学意义(F=37.37、9.08,P值均＜0.05).FKN-siRNA转染后,SW-1990和PNAC-1细胞中,FKN蛋白(F=118.93、88.62)和mRNA(F=47.91、72.59)表达水平下降,同时TNF-α和IL-6的蛋白(FTNF-α=112.90、77.88,FIL-6=165.27、286.49)和mRNA(FTNFα=47.93、45.19,FIL-6=36.41、23.67)表达水平增高,差异均有统计学意义(P均＜0.05).结论 应用siRNA技术静默趋化因子FKN的功能后,胰腺癌细胞株的增殖活性和侵袭力增强,表明FKN可能抑制了胰腺癌细胞的生物学活性.     

RNA干扰沉默NF-κB p65基因表达抑制胰腺癌PANC1细胞增殖与侵袭的研究

目的 运用RNA干扰技术阻断人胰腺癌细胞株PANC1的NF-κB p65表达,观察该基因沉默后对细胞增殖能力及体外侵袭能力的影响.方法 采用阳离子脂质体LipofectamineTM 2000将化学合成的人NF-κB p65的小干扰RNA(siRNA)转染人胰腺癌细胞PANC1作为siRNA组,另设无同源性siRNA转染细胞的阴性对照组和蒸馏水空白对照组.实验重复6次.应用RT-PCR检测转染细胞NF-κB p65 mRNA与细胞间黏附分子-1(ICAM-1)mRNA的表达.MTT结合克隆形成实验测定细胞生长抑制率.Matrigel细胞侵袭实验测定细胞体外侵袭能力.结果 siRNA组、阴性对照组和空白对照组NF-κB p65 mRNA相对表达量分别为0.227±0.045、0.381±0.038和0.404±0.031;ICAM-1 mRNA相对表达量分别为0.597±0.083、0.983±0.068和1.027±0.098;细胞生长抑制率(72 h)分别为18.3%、2.3%和0;克隆形成率分别为(14.1±3.1)%、(24.5±2.1)%和(27.2±2.6)%;侵袭细胞数分别为80.25±6.35、123.83±8.80和127.68±9.23.siRNA组均明显低于2个对照组(P＜0.01).结论 NF-κB p65的RNA干扰能抑制胰腺癌PANC1细胞NF-κB p65 mRNA和ICAM-1 mRNA的表达,抑制细胞的生长和侵袭.     

人类真核延伸因子1A2对胰腺癌细胞侵袭、转移能力的影响

目的 探讨外源性人类真核延伸因子(EEF)1A2基因导入人胰腺癌SW1990细胞株后.细胞侵袭转移能力的改变.方法 应用腺病毒载体将EEF1A2基因导入人胰腺癌SW1990细胞中,采用划痕实验、Transwell小室、细胞粘附实验检测转染前后细胞运动、侵袭、转移及粘附能力的改变.结果 Ad5/F35-EEF1A2转染后继续培养48 h的SW1990细胞,可见预期大小的特异性条带.实验组24 h后细胞迁移率为(74.43±2.12)%,与阴性对照组和空白对照组比较差异有统计学意义[(44.08±5.92)%和(48.09±3.54)%,P＜0.05].实验组48 h后穿膜细胞数为(65.42±8.24)个,与阴性对照组和空白对照组相比差异有统计学意义[(20.10±5.82)个和(23.25±5.23)个,P＜0.05].实验组48 h后穿膜细胞数为(61.30±5.68)个,与阴性对照组和空白对照组相比差异有统计学意义[(32.04±3.60)个和(32.33±2.51)个,P＜0.05],且对Ⅰ型、Ⅱ型、Ⅳ型胶原、纤维结合蛋白、粘蛋白的粘附力增强(P＜0.05).结论 腺病毒介导的EEF1A2高表达能明显增强胰腺癌SW1990细胞的运动、侵袭、转移及粘附能力.提示EEF1A2可能通过改变胰腺癌细胞的生物学特性影响胰腺癌的发生发展.     

靶向性沉默DNMT1基因对胰腺癌细胞DNA甲基化的影响

目的 观察DNA甲基转移酶1(DNMT1)基因沉默后对人胰腺癌PaTu8988细胞的DNMT活性及hMLH-1基因CpG岛DNA甲基化状态的影响.方法 由美国Ambion公司设计合成DNMT1siRNA和阴性对照siRNA,分别用15、30 nmol/L的浓度转染胰腺癌PaTu8988细胞,以未转染组细胞作为对照.应用实时PCR和蛋白质印迹法检测DNMT1 mRNA和蛋白的表达;用DNMT活性检测试剂盒检测其活性;用亚硫酸氢盐测序PCR(BSP)法检测hMLH-1基因CpG岛的甲基化状态;实时PCR法检测hMLH-1 mRNA的表达.结果 转染48 h后,DNMT1 siRNA15、30 nmol/L组细胞DNMT1 mRNA表达量分别为0.573±0.026和0.143±0.044,显著低于对照组的1.020±0.217及阴性siRNA 15、30 nmol/L组的0.900±0.475和0.938±0.327(P值均＜0.05);DNMT1 siRNA组的DNMT1蛋白表达亦低于对照组和阴性siRNA组.DNMT1 siRNA15、30 nmol/L组细胞DNMT活性分别为0.364±0.124和0.250±0.072,明显低于对照组的0.931±0.065及阴性siRNA 15、30 nmol/L组的0.665±0.055和0.472±0.040.DNMT活性与DNMT1 mRNA表达呈正相关(r=0.69,P＜0.01).DNMT1 RNA干扰后导致hMLH-1基因CpG位点的8个甲基化减少到1个甲基化.结论 DNMT1 siRNA能特异性抑制胰腺癌PaTu8988细胞DNMT1基因的表达,明显抑制DNMT的活性,并引起hMLH-1基因CpG岛去甲基化.     

TLR4 shRNA质粒的构建及稳定转染人胰腺癌PANC1细胞株的筛选

目的 构建靶向人TLR4基因的短发夹RNA(shRNA)真核表达质粒,转染胰腺癌细胞,并筛选出稳定转染的克隆细胞株.方法 采用小分子干扰RNA(siRNA)软件设计3个靶向TLR4基因的shRNA,构建3个质粒表达载体,分别命名为TLR4-1、TLR4-2、TLR4-3;选取抑制效率最高的shRNA质粒,采用脂质体法转染胰腺癌PANC1细胞;实时定量PCR和流式细胞技术检测细胞TLR4 shRNA基因沉默效率和转染效率;G418抗性筛选和有限稀释单克隆形成法挑选培育稳定转染TLR4 shRNA的单克隆细胞系.结果 转染48 h后PANC1细胞瞬时转染效率为(46.72±5.06)％.转染TLR4-1、TLR4-2、TLR4-3的细胞的TLR4mRNA表达水平分别为0.025±0.004、0.027±0.003、0.019±0.006,均显著低于未转染组的0.061±0.018和阴性对照转染组的0.057±0.015(P值均＜0.05).以沉默效果最佳的TLR4-3转染细胞所获得的稳转细胞的转染效率为(82.79 ±8.16)％,较瞬转细胞显著提高(P=0.001);TLR4 mRNA表达水平为0.010±0.002,较瞬转细胞显著下调(P=0.001);TLR4蛋白表达率为(0.54±0.32)％,显著低于未转染细胞的(87.42±5.00)％和转染阴性对照细胞的(82.90±5.00)％(P=0.000).结论 成功筛选到TLR4基因沉默的稳转PANC1细胞.     

胰腺癌细胞TM4SF1的表达及其对细胞增殖、迁移及侵袭能力的影响

目的 检测5株人胰腺癌细胞株中TM4SF1 mRNA的表达,探讨TM4SF1基因对癌细胞增殖、迁移及侵袭能力的影响.方法 采用实时PCR方法检测人胰腺癌细胞株MPanc96、MiaPaCa-2、HPAC、PANC1、AsPC-1的TM4SF1 mRNA表达,并与人正常胰腺导管上皮细胞（HPDE）的TM4SF1mRNA表达进行比较.应用RNA干扰方法将靶向TM4SF1的siRNA及阴性对照siRNA瞬时转染MPanc96、MiaPaCa-2细胞.采用MTS法检测转染细胞的增殖能力,Transwell小室法检测细胞的迁移及侵袭能力.结果 胰腺癌细胞株MPanc96、MiaPaCa-2、PANC1、AsPC-1、HPAC的TM4SF1 mRNA相对表达量分别为1.205±0.073、1.096±0.260、1.382±0.075、1.374±0.363、0.744±0.096,均显著高于HPDE的0.020±0.003（F =22.26,P＜0.01）.与转染阴性对照siRNA的细胞比较,TM4SF1基因表达沉默的MPanc96、MiaPaCa-2细胞的增殖无显著变化,但细胞的迁移力分别降低（62.5±7.6）％、（72.8±4.0）％,侵袭能力分别下降（69.5±5.7）％、（78.6±6.3）％.结论 TM4SF1在人胰腺癌细胞中高表达,并增强胰腺癌细胞的迁移和侵袭能力.     

HDAC1基因沉默对人胰腺癌细胞PaTu8988细胞周期的影响

目的 探讨组蛋白脱乙酰基酶1( HDAC1)基因沉默对人胰腺癌PaTu8988细胞周期影响及可能机制.方法 常规培养胰腺癌PaTu8988细胞,分为对照组、阴性siRNA转染(c-siRNA)组及15、30 nmol/L HDAC1 siRNA转染组.采用脂质体2000转染细胞48 h后,应用蛋白质印迹法检测细胞HDAC1基因沉默效率及p21基因表达;流式细胞法检测细胞周期的变化.结果 与对照组比较,30 nmol/L HDAC1 siRNA组PaTu8988细胞的HDAC1蛋白表达明显下降,P21蛋白表达明显增加;G2/M 期细胞比例显著减少[(21.48±3.67)％比(28.28±2.94)％,P＜0.05],S期细胞比例显著增加[(50.20±6.85)％比(32.49±2.78)％,P＜0.05].结论 HDACl siRNA能特异、有效地抑制人胰腺癌PaTu8988细胞HDACl的表达,引起细胞S期阻滞,其机制可能与上调p21蛋白表达有关.     

胰岛素瘤的解剖分布特点分析

目的胰岛素瘤是最常见的胰腺神经内分泌肿瘤，因其临床表现多样，导致诊断困难。影像学诊断尤其是超声内镜(EUS)在胰岛素瘤的诊断中起着重要作用，拥有较高的敏感性和特异性。本研究拟通过明确胰岛素瘤的解剖分布特点，以期有助于提高影像学的诊断准确率和降低漏诊率，尤其是在教育和培训实践中对于EUS的学习者更具有指导价值。 方法回顾性分析解放军总医院第一医学中心病案资料数据库1993年1月至2019年11月经外科手术、病理确诊为胰岛素瘤的患者的临床资料，检索方法采取搜索术后病理诊断为"胰岛素瘤"的病例，通过查阅病例的方法，提取出胰岛素瘤的大小和解剖分布等数据，进一步分析其特点。 结果共检索到确诊为胰岛素瘤的患者116例，其中，男45例、女71例，年龄13～76岁，平均年龄(44.4±14.85)岁。胰岛素瘤单发110例(94.8%)、多发6例(5.2%)。位置分布：头颈部46例(39.7%)，单发45例、多发1例；体尾部68例(58.6%)，单发65例、多发3例；全胰腺多发2例(1.7%)。病变大小特点：最大径0.4～3.4 cm，平均大小(1.53±0.58)cm。≤1 cm 29例、>1 cm而≤1.5 cm41例、>1.5 cm而≤2.0 cm28例，≤3 cm 15例，>3 cm 3例。年龄与肿瘤的大小相关，≤44岁患者肿瘤平均大小为(1.36±0.51)cm、>44岁患者肿瘤平均大小为(1.70±0.60)cm，P<0.05。头颈部的肿瘤大于体尾部的肿瘤，头颈部肿瘤平均大小(1.66±0.63)cm，体尾部(1.42±0.52)cm，P<0.05。 结论胰岛素瘤在胰腺体尾部较头颈部更好发；绝大多数单发，但可以全胰腺多发；多数小于1.5 cm，肿瘤的大小与患者年龄和肿瘤的解剖分布相关。     

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7?, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20?, MUC2?). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Demonstration of the mechanism of action of biguanides

Summary Palmitic acid oxidation in rat diaphragm homogenate is depressed by biguanide concentrations that are still incapable of inhibiting oxidative phosphorylation. Glucose oxidation is not directly effected by the same biguanide concentrations: however, the inhibitory effect of palmitic acid on glucose oxidation is partly removed by biguanides. Inhibition of fatty acid oxidation, which accounts for most of the metabolic effects caused by these drugs, can be regarded as the fundamental mechanism of action of biguanides. There is some evidence suggesting that these drugs might interact with carnitine, thus preventing long-chain fatty acids from being transported across the mitochondrial membrane to the site of oxidation. Traduzione a cura degli AA.     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

血吸虫童虫生长发育及其机制的研究进展

血吸虫童虫是宿主免疫系统攻击的重要靶标,包括皮肤型、肺型和肝门型童虫。宿主分子对童虫生长发育具有重要作用。童虫生长发育机制包括免疫调节、信号转导、性别发育及凋亡等。肌动蛋白、组织蛋白酶、烯醇化酶和葡萄糖基转移酶等分子为血吸虫童虫生长发育的重要分子。本文对血吸虫童虫生长发育及其机制的研究进展做一综述。     

124例耐多药结核分枝杆菌基因突变特征分析

目的对临床分离的耐多药结核分枝杆菌相关基因的突变特征进行分析。方法对124例耐多药结核分枝杆菌以及50株敏感株的耐药相关基因(包括异烟肼inh A、kat G、oxyR-ahp C间隔区以及利福平rpo B)进行序列测定,分析其基因突变情况。结果异烟肼耐药inh A基因突变率为14.5%;kat G基因突变率为70.2%(87/124),主要位于315位;oxyR-ahp C间隔区突变率为15.3%;inh A、kat G两种基因同时突变率75.0%,三种基因同时突变率为89.5%。利福平rpo B基因突变的检出率高达95.2%,突变主要发生在531、526、516位点。结论我省耐多药菌异烟肼耐药相关基因最常见突变为kat G 315、inh A C-T(-15)、axyR-ahp C间隔区(-10)C-T,利福平为rpo B531、526、516。结合MDR-TB耐药相关基因的特征分析,可以建立一种快速、准确、特异的适合于我省的检测结核菌耐多药性的新方法。     

氯硝柳胺悬浮剂的毒性评价

目的评价氯硝柳胺悬浮剂的毒性，为现场大规模应用灭螺提供依据。方法按照中华人民共和国国家标准GB 15670-1995《农药登记毒理学试验方法》和鱼类毒性试验方法进行。结果经口、经皮肤的LDso雌、雄性大鼠均>5 000 mg/kg，经呼吸道的LCso雌、雄性大鼠均>5 000mg/m3，该药经口、经皮肤、经呼吸道毒性均属微毒类药物；兔眼用药后，观察期内无不良反应，对眼无刺激性；皮肤用药后对皮肤无刺激性。与氯硝柳胺原药、氯硝柳胺乙醇胺盐原药和氯硝柳胺乙醇胺盐可湿性粉剂相比，氯硝柳胺悬浮剂对鱼急性毒性最低。结论氯硝柳胺悬浮剂属微毒类药物，对鱼的毒性低于其乙醇胺盐可湿性粉剂，适合于现场应用。     

Assessment of quality of life of parents of children with juvenile chronic arthritis

The aim of the study was to assess the quality of life (QOL) and the psychological status of parents of children with juvenile chronic arthritis (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA were evaluated and compared to those of the parents of 28 healthy children. Mothers of JCA children and mothers of healthy children reported similar QOL. The reported anxiety and depression levels were similar for mothers and fathers in both groups. The parents of children with pauciarticular-type JCA reported lower QOL and higher levels of anxiety and depression than the parents of children with other types, namely polyarticular and systemic JCA. These findings may be explained by the fact that the pauciarticular patients had shorter disease duration and were less frequently seen in the outpatient clinic. The QOL of mothers of children with JCA was found to be slightly impaired in the group of children with pauciarticular JCA. Future larger studies are needed to confirm these results, as the number of subjects in the three groups was rather low. Received: 26 September 2001 / Accepted: 8 February 2002     

治疗高血压药物的经济学评价

重视高血压治疗中的经济学评价,对利用我国有限的卫生资源来遏制高血压对人民群众的危害有着重要的现实意义。药物经济学对于药物治疗的成本和治疗的结果给予同样的关注。因为治疗高血压的费用,不仅涉及药物价格,还包括患者的危险水平,降压疗效和对临床终点事件的影响,以及治疗的依从性和安全性。因此药物经济学更强调整体成本和价-效比。低危病人,若非药价低廉,治疗的价-效比不够理想。而在高危的患者,价-效比越小越经济而不是药费越便宜越好。     

Numerical Simulation of the Effect of Rate of Change of Glucose on Measurement Error of Continuous Glucose Monitors

Background

A 5-day in-patient study designed to assess the accuracy of the FreeStyle Navigator® Continuous Glucose Monitoring System revealed that the level of accuracy of the continuous sensor measurements was dependent on the rate of glucose change. When the absolute rate of change was less than 1 mg•dl⁻¹•min⁻¹ (75% of the time), the median absolute relative difference (ARD) was 8.5%, with 85% of all points falling within the A zone of the Clarke error grid. When the absolute rate of change was greater than 2 mg•dl⁻¹•min⁻¹ (8% of the time), the median ARD was 17.5%, with 59% of all points falling within the Clarke A zone.

Method

Numerical simulations were performed to investigate effects of the rate of change of glucose on sensor measurement error. This approach enabled physiologically relevant distributions of glucose values to be reordered to explore the effect of different glucose rate-of-change distributions on apparent sensor accuracy.

Results

The physiological lag between blood and interstitial fluid glucose levels is sufficient to account for the observed difference in sensor accuracy between periods of stable glucose and periods of rapidly changing glucose.

Conclusions

The role of physiological lag on the apparent decrease in sensor accuracy at high glucose rates of change has implications for clinical study design, regulatory review of continuous glucose sensors, and development of performance standards for this new technology. This work demonstrates the difficulty in comparing accuracy measures between different clinical studies and highlights the need for studies to include both relevant glucose distributions and relevant glucose rate-of-change distributions.