胶原性关节炎大鼠滑膜组织细胞因子基质金属蛋白酶3和组织金属蛋白酶抑制剂1表达的变化

目的:观察Ⅱ型胶原诱导的实验性关节炎动物模型组织细胞因子基质金属蛋白酶3和组织金属蛋白酶抑制剂1表达的变化,探讨基质金属蛋白酶3和组织金属蛋白酶抑制剂1在类风湿关节炎发病机制中的作用。方法:实验于2005-09/2006-11在白求恩国际和平医院中心实验室完成。①实验分组:健康雄性Wistar大鼠60只,体质量(100±20)g,随机选出50只以备造模,另外10只作为对照组。在造模成功的大鼠中再随机选出10只作为模型组。②实验方法:采用10mg牛Ⅱ型胶原与100mg弗氏不完全佐剂和60mg卡介苗充分研磨后,以每支每点0.1～0.2mL(1g/L)从大鼠背部尾根部多点皮下注射,于10d后按上述方法和剂量再次重复免疫和制作大鼠胶原性关节炎模型。③实验评估:初次免疫后7周,剥离膝关节滑膜,进行苏木精-伊红染色光镜下观察;切除另侧膝关节滑膜,免疫组织化学染色后,用Metamorph图像分析系统进行检测,计算每个视野基质金属蛋白酶3和组织金属蛋白酶抑制剂1的阳性面积比,以其作为阳性反应细胞密度。结果:纳入大鼠60只,20只进入结果分析。模型组大鼠关节组织中的基质金属蛋白酶3阳性密度为0.75±0.19,明显高于对照组,差异有显著性意义(P<0.01);组织金属蛋白酶抑制剂1的表达阳性密度为0.48±0.17,与对照组0.78±0.21比较明显降低,差异有显著性意义(P<0.01)。结论:细胞因子基质金属蛋白酶3和组织金属蛋白酶抑制剂1表达的变化与胶原性关节炎大鼠的发病相关。     

Information‐based sample size re‐estimation in group sequential design for longitudinal trials

Group sequential design has become more popular in clinical trials because it allows for trials to stop early for futility or efficacy to save time and resources. However, this approach is less well‐known for longitudinal analysis. We have observed repeated cases of studies with longitudinal data where there is an interest in early stopping for a lack of treatment effect or in adapting sample size to correct for inappropriate variance assumptions. We propose an information‐based group sequential design as a method to deal with both of these issues. Updating the sample size at each interim analysis makes it possible to maintain the target power while controlling the type I error rate. We will illustrate our strategy with examples and simulations and compare the results with those obtained using fixed design and group sequential design without sample size re‐estimation. Copyright © 2014 John Wiley & Sons, Ltd.     

Hepcidin对小鼠脑组织中铁沉积及运动行为能力的影响

目的：观察hepcidin对小鼠脑组织铁沉积及运动行为能力的影响,并探讨其作用机制。方法：将雌雄各半的昆明小鼠随机分为7组,分别为空白对照组、铁负荷组（2mg·ml^-1、1mg·ml^-1、0.5mg·ml^-1）、hepcidin 5μg＋铁负荷组（2mg·ml^-1、1mg·ml^-1、0.5mg·ml^-1）,以不同浓度的右旋糖酐铁隔日大腿肌肉注射建立铁过载模型。8周后,血细胞计数仪检测血液中血红蛋白含量,全自动生化分析仪检测血清铁含量,试剂盒检测血清中转铁蛋白（Tf）和总铁结合力（TIBC）;原子吸收光谱法检测测定脑组织中铁的含量;ROS试剂盒检测脑组织中活性氧簇（Reactive oxygen species,ROS）含量;Morris水迷宫实验观察小鼠运动行为的改变。结果：与空白对照组比较,铁负荷组小鼠血清铁及血红蛋白含量明显增加,转铁蛋白（Tf）和总铁结合力（TIBC）明显减少,小脑、中脑和纹状体中铁含量和ROS明显升高,且呈剂量依赖性;Morris水迷宫实验结果显示,铁负荷组小鼠与空白对照组比较,平均逃逸时间明显增加,而靶象限活动时间明显下降（p〈0.05）;而hepcidin组均出现相反方向变化：hepcidin组小鼠平均逃逸时间明显下降,而靶象限活动时间明显增加。结论：铁过负荷对小鼠小脑、中脑和纹状体造成明显毒性损害,并引起脑的氧化应激,认知行为和空间记忆力下降;而hepcidin可抑制铁负荷引起的脑铁沉积和运动行为能力变化。     

Rapid prenatal diagnosis of beta thalassemia using DNA amplification and nonradioactive probes

We used in vitro DNA amplification by the polymerase chain reaction and nonradioactive probes for prenatal diagnosis of beta thalassemia in Chinese from the Guangdong province. Exact molecular diagnoses were made in all 20 fetuses studied over a 6-month period. We conclude that this method of prenatal diagnosis for beta thalassemia is a viable approach in many parts of the world where this disease is common.     

Tegillarca granosa extract Haishengsu (HSS) suppresses expression of mdr1, BCR/ABL and sorcin in drug-resistant K562/ADM tumors in mice

PurposeTo evaluate the effect of Haishengsu (HSS), a protein extract from Tegillarca granosa, on multidrug-resistance genes mdr1, BCR/ABL and sorcin in transplanted tumors.Material/MethodsMice were inoculated subcutaneously with a drug resistant leukemia cell line K562/ADM. Tumor-bearing animals were divided into control, adriamycin, HSS and combination therapy (adriamycin plus HSS) groups. Flow cytometry was used to detect apoptosis of tumor cells, and RT-PCR was used to evaluate the expression of mdr1, BCR/ABL and sorcin.ResultsThe apoptosis rate in the high (71.8%), medium (72.3%) and low doses HSS group (72.4%) was higher than in control (1.2%, p<0.01), adriamycin (34.4%, p<0.05) or combination therapy group (46.4%, p<0.05). The mean optical density of mdr1, BCR/ABL and sorcin in HSS groups was lower than in control, adriamycin and combination therapy group (p<0.01). The optical density of the three genes in high HSS group was lower than in medium and low HSS group (p<0.01).ConclusionsHaishengsu promotes apoptosis of drug-resistant K562/ADM tumors in mice in a dose-dependent manner. The pro-apoptotic effect of Haishengsu may be related to a reduced expression of multidrug-resistance genes mdr1, BCR/ABL and sorcin.     

Four categories of gamma-globin gene triplications: DNA sequence comparison of low G gamma and high G gamma triplications

The human fetal gamma chains are produced by closely linked G gamma and A gamma genes, and unequal crossing over between them leads to gamma gene deletions and triplications. Nine gamma gene triplications from seven ethnic groups were analyzed for G gamma and hemoglobin F (Hb F) values of heterozygotes and for the presence of polymorphic XmnI restriction sites 5' to the gamma genes. Four categories of triplication were found: I had low G gamma and low Hb F values and lacked XmnI sites 5' to the three gamma genes [---]. II had high G gamma and slightly elevated Hb F values but was also [---]. III was similar to II, except that XmnI was [+--]. IV had very high G gamma and slightly elevated Hb F values, and XmnI was [++-]. One case each of triplications I and IV were cloned into Charon 35. For both, the two 5' gamma gene code for G gamma chain, while the 3' gamma gene codes for A gamma chain. DNA sequencing showed that the unequal crossover occurred between 472 and 398 base pairs (bp) 5' to the gamma gene Cap sites (- 472 and -398) for the type IV triplication and between -271 and codon 136 for the type I triplication. In addition, type I had a 4-bp deletion of AGCA from -225 to -222. The high G gamma values of the type IV triplication are explained by its -G gamma-G gamma-A gamma-gene arrangement and the XmnI sites 5' to the G gamma genes. We hypothesize that the low G gamma value of the type I triplication, which is also -G gamma-G gamma-A gamma-, is due to inactivation of the middle G gamma gene by the AGCA deletion at -225 to -222.     

Effects of sera from burn patients on human hepatocytic viscoelasticity

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