131I联合糖皮质激素治疗Graves眼病疗效的Meta分析

目的 对131I+糖皮质激素（GC）治疗Graves眼病（GO）进展的有效性和安全性进行系统评价。 方法 检索PubMed、Embase、Cochrane Library和中国知网、万方数据知识服务平台中关于131I+GC治疗GO的相关研究,检索时间从建库至2021年7月20日。根据纳入和排除标准筛选文献、提取数据。应用Stata 15.0软件进行Meta分析,比较131I+GC治疗与单纯131I治疗对不同时期 Graves 甲状腺功能亢进症（GH）合并GO患者的疗效,并分析静脉注射与口服GC 2种用药方式对GO治疗及其并发症发生情况的影响。采用χ2检验的P值和 I2对文献进行异质性评价,GO病情进展情况用相对危险度（RR）表示,采用Egger法和剪补法对纳入文献的发表偏倚和敏感性进行分析,采用Z检验分析2种用药方式的治疗效能。 结果 最终纳入22篇文献,其中15篇文献为随机对照试验类,7篇文献为队列研究类。131I+GC治疗较131I治疗对GH合并GO患者的疗效更佳,差异有统计学意义（Z=3.18,RR=0.37,95%CI:0.20~0.68,P=0.004）;标准剂量GC（0.3~0.5 mg/kg）较低剂量GC（0.2~0.3 mg/kg）能更好地预防GO的进展。不同的用药方式对预防GO进展的影响不大。 结论 131I+GC治疗对预防GH合并GO患者的病情进展是有效的,特别是活动期的GO患者;标准剂量GC较低剂量GC能更好地控制GO的进展,但同时产生更多的并发症;静脉注射与口服GC 2种用药方式对131I治疗后的GO患者疗效相当。     

阿尔茨海默病与帕金森病痴呆病人的ASL脑灌注研究

目的 利用三维伪连续动脉自旋标记（3D pcASL）成像技术比较阿尔茨海默病（AD）和帕金森病痴呆（PDD）病人脑灌注的异同,并分析脑灌注改变与认知功能损害的相关性。 方法 前瞻性收集AD病人24例、PDD病人26例、正常对照（NC）36例,均行颅脑常规MRI及3D pcASL灌注MRI检查。采用基于Matlab的SPM12软件对3D pcASL序列扫描获得的脑血流（CBF）图进行预处理,通过单因素协方差分析及独立样本t检验进行组间比较。利用DPABI软件提取AD组与NC组、PDD组与NC组灌注存在差异脑区的相对脑血流量（rCBF）值,采用Pearson相关方法对rCBF值与简易精神状态量表（MMSE）及蒙特利尔认知评估量表（MoCA）评分做相关性分析。 结果 与NC组相比,AD组双侧大脑皮质的广泛区域灌注减低,双侧丘脑、基底节、海马及辅助运动区（SMA）灌注增高;PDD组表现为与AD组基本一致的灌注减低和增高的脑区,但是脑区变化范围缩小。与AD组相比,PDD组双侧壳核、左侧中央前回、右侧SMA灌注减低,右侧顶下小叶灌注增高。AD组左侧额中回及左侧颞中回的灌注值与MMSE评分（分别r=0.64,P<0.001;r=0.50,P=0.01）及MoCA评分（分别r=0.44,P=0.03;r=0.48,P=0.02）均呈正相关,PDD组相关脑区与认知评分未见显著相关性。 结论 3D pcASL成像技术能够直观地反映AD与PDD病人类似的脑血流灌注模式,同时显示两者的灌注差异。AD病人多个脑区灌注值与认知相关评分呈正相关,提示脑血流改变与认知损伤具有相关性。     

抗咯萘啶的伯氏疟原虫感染红细胞多胺量的测定

目的：了解疟原虫的多胺代谢与咯萘啶（ＰＮＤ）抗药性的关系。方法：感染伯氏疟原虫ＡＮＫＡ株（ＰＳ）和由该株培育的中抗ＰＮＤ品系（ＰＲＡ）及高抗ＰＮＤ品系（ＰＲＢ）的昆明株小鼠于腹腔接种（ｉｐ）后ｄ７取血，经薄层层析后用荧光分光光度法测定正常ＲＢＣ、ＰＳ、ＰＲＡ和ＰＲＢ感染ＲＢＣ的丁二胺（ＰＴＣ）、精脒（ＳＰＤ）和精胺（ＳＰＭ）量。另有感染ＰＳ和ＰＲＢ的小鼠于ｉｐ后ｄ６分别１次灌胃（ｉｇ）ＰＮＤ５ｍｇ／ｋｇ和１０ｍｇ／ｋｇ，ｄ７取血，按上述方法测定给药后感染ＲＢＣ的多胺量，并与不给药组比较。结果：ＰＳ感染ＲＢＣ的多胺量均明显高于未感染疟原虫的正常ＲＢＣ，而感染ＰＲＡ和ＰＲＢ的ＲＢＣ多胺量又显著高于ＰＳ感染ＲＢＣ，且多胺量的增高与抗性程度有关。经ＰＮＤ治疗后ＰＳ感染ＲＢＣ的ＳＰＤ和ＳＰＭ较未治疗组显著下降，而ＰＲＢ感染ＲＢＣ则未见明显变化。结论：伯氏疟原虫对ＰＮＤ的抗药性与其多胺代谢有关。     

Relation of spontaneous transformation in cell culture to adaptive growth and clonal heterogeneity.

Cell transformation in culture is marked by the appearance of morphologically altered cells that continue to multiply to form discrete foci in confluent sheets when the surrounding cells are inhibited. These foci occur spontaneously in early-passage NIH 3T3 cells grown to confluency in 10% calf serum (CS) but are not seen in cultures grown to confluency in 2% CS. However, repeated passage of the cells at low density in 2% CS gives rise to an adapted population that grows to increasingly higher saturation densities and produces large numbers of foci in 2% CS. The increased saturation density of the adapted population in 2% CS is retained upon repeated passage in 10% CS, but the number and size of the foci produced in 2% CS gradually decrease under this regime. Clonal analysis confirms that the focus-forming potential of most if not all of the cells in a population increases in response to a continuously applied growth constraint, although only a small fraction of the population may actually form foci in a given assay. The acquired capacity for focus formation varies widely in clones derived from the adapted population and changes in diverse ways upon further passage of the clones. We propose that the adaptive changes result from progressive selection of successive phenotypic variations in growth capacity that occur spontaneously. The process designated progressive state selection resolves the apparent dichotomy between spontaneous mutation with selection on the one hand and induction on the other, by introducing selection among fluctuating states or metabolic patterns rather than among genetically altered cells.     

抗胃癌抗体重链可变区序列分析及空间结构模拟

目的:通过序列分析确定抗胃癌抗体重链可变区(VH)的一级结构,并借助同源模建方法模拟其三级结构.方法:从抗人胃癌噬菌体抗体库中筛选出VH基因,并进行序列测定、翻译和分析.利用计算机辅助蛋白质空间模拟技术,采用同源模建、力学优化合理模建VH的三维空间结构.结果:序列比对分析表明获得的VH序列符合鼠抗体可变区特征,通过Kabat分析确定了FR、CDR;合理搭建了抗体重链可变区的空间构象,并通过分子力学优化获得了稳定的三维结构.结论:所测得的VH一级结构和构建的三维空间结构均有较高的可靠性,为进一步的生物学实验奠定了基础.     

Isolation of drug-resistant variants of HIV-1 from patients on long-term zidovudine therapy. Canadian Zidovudine Multi-Centre Study Group

We determined whether drug-resistant variants of HIV-1 could be isolated from the peripheral blood mononuclear cells of 20 individuals with HIV infection (Centers for Disease Control groups II and III) on long-term zidovudine (AZT) therapy. Toward this end, zidovudine (10 microM) has been included in the tissue culture medium used to isolate HIV-1. Under these circumstances, virus with a zidovudine-resistant phenotype was successfully obtained in five out of 20 cases. This property of drug resistance appeared to be stable, and did not disappear upon extended replication of such virus in the absence of drug pressure. Drug-resistant virus could also be isolated from these subjects on subsequent occasions, but was not present in samples obtained prior to therapy. Replication of these zidovudine-resistant isolates in tissue culture was inhibited by each of four other nucleoside analogues. Thus, other drugs may be useful in controlling selective zidovudine-resistant variants of HIV-1.     

高灵敏度薄膜生物传感器基因芯片系统的研制

目的: 在传统基因芯片技术基础上, 应用生物传感器技术, 研制一种能将基因芯片信号原位放大后达肉眼判读灵敏度, 无需专用基因芯片检测仪器就可使用, 易于在基层医疗单位推广的薄膜生物传感器基因芯片诊断系统.方法:在薄膜生物传感器基片基础上, 经过表面化学处理, 使特定的基因捕获探针在传感器表面固定, 形成特定检测目的生物传感器基因芯片. 并以乙肝病毒YMDD区的特异序列设计为例, 通过特定的YMDD区的捕获探针, 以矩阵的形式点样于传感器芯片表面来实现本系统. 同时, 纳米金标记的检测探针取代了传统芯片中的荧光标记探针. 扩增后的目的PCR片段与捕获探针、生物素标记探针、链亲蛋白纳米金探针进行反应, 最后得到探针-生物素-链亲蛋白-纳米金复合物, 并在芯片表面经生物传感器芯片将信号原位放大, 获得肉眼观的芯片信号并进行分析, 完成芯片诊断. 以乙型肝炎病毒YMDD突变为例, 观察该芯片系统对临床诊断标本诊断的可靠性.结果: 基因芯片的检测信号经生物传感器原位放大后能肉眼判读或借助普通数码照像机或计算机扫描, 根据信号出现的特定位置即可确定突变的类型. 且该生物传感器基因芯片系统信噪比高, 在人工合成的寡核苷酸及临床血清的检测中, 均可实现生物芯片阴阳性信号完全的有或无的判读; 临床血清标本检测证实, 使用该传感器芯片系统对前期经过测序确定为YMDD突变的23份临床血清结果与测序结果完全一致. 结论:薄膜生物传感器基因芯片集纳米材料、生物传感器技术及原位放大技术为一体, 实现了信号的肉眼判读, 具有通用性高, 准确可靠, 无需大型设备, 易于在基层医疗单位推广使用.     

Suppressive oligodeoxynucleotides inhibit atherosclerosis in ApoE(-/-) mice through modulation of Th1/Th2 balance

Atherosclerosis is a chronic inflammatory disease, which is positively and negatively regulated by T helper (Th) 1 and Th2 lymphocytes, respectively. Recent findings indicate that suppressive oligodeoxynucleotides (ODNs) expressing TTAGGG motifs selectively reduce Th1 cytokine production and have been proven effective at blocking the development of organ-specific autoimmune diseases. In the current research, we hypothesized that suppressive ODNs may alter the development of atherosclerosis. Eight-week-old homozygous ApoE^−/− male mice were injected with 300 μg ODNs A151 (TTAGGG) or nonspecific ODNs 1612. Atherosclerotic lesion sizes were dramatically reduced by ODNs A151, but not by nonspecific ODNs. MCP-1 and VCAM-1, which are the key inflammatory factors in atherogenesis, were significantly attenuated by the suppressive ODNs A151. In the splenic lymphocytes, FACS analysis showed ODNs A151 reduced the percentage of IFN-γ-producing Th1 cells and slightly increased the percentage of IL-4-producing Th2 cells, indicating that suppressive ODNs skewed the Th1/Th2 balance toward Th2 inflammation in vivo. Furthermore, ODNs A151 down-regulated the phosphorylation of STAT1 and STAT4 and suppressed up-regulation of T-bet, a signal modulator for Th1, and didn't impact GATA-3 and STAT6, which are associated with a Th2 phenotype. Consistent with this in vivo observation, ELISA analysis demonstrated that ODNs A151 suppressed Th1 cytokines IFN-γ and TNF-α, and augmented Th2 cytokines IL-4 and IL-10 in vitro. This study provides the first experimental evidence that suppressive ODNs inhibit the development of atherosclerosis through inhibition of the STAT1/4 and T-bet pathways, which further modulate the Th1/Th2 balance in vivo.     

Liver fibrosis in chronic viral hepatitis： An ultrasonographic study

AIM: To select valuable ultrasonographic predictors for the evaluation of hepatic inflammation and fibrosis degree in chronic hepatitis, and to study the value of ultrasonography in the evaluation of liver fibrosis and compensated liver cirrhosis in comparison with serology and histology. METHODS: Forty-four ultrasonographic variables were analyzed and screened using color Doppler ultrasound system in 225 patients with chronic viral hepatitis and compensated liver cirrhosis. The valuable ultrasonographic predictors were selected on the basis of a comparison with histopathological findings. The value of ultrasonography and serology in the evaluation of liver fibrosis degree and the diagnosis of compensated liver cirrhosis was also studied and compared. Meanwhile, the influencing factors on ultrasonographic diagnosis of compensated liver cirrhosis were also analyzed. RESULTS: By statistical analysis, the maximum velocity of portal vein and the degree of gall-bladder wall smoothness were selected as the valuable predictors for the inflammation grade (G), while liver surface, hepatic parenchymal echo pattern, and the wall thickness of gall-bladder were selected as the valuable predictors for the fibrosis stage (S). Three S-related independent ultrasonographyic predictors and three routine serum fibrosis markers (HA, HPCIII and CIV) were used to discriminate variables for the comparison of ultrasonography with serology. The diagnostic accuracy of ultrasonography in moderate fibrosis was higher than that of serology (P<0.01), while there were no significant differences in the general diagnostic accuracy of fibrosis as well as between mild and severe fibrosis (P<0.05). There were no significant differences between ultrasonography and serology in the diagnosis of compensated liver cirrhosis. However, the diagnostic accuracy of ultrasonography was higher in inactive liver cirrhosis and lower in active cirrhosis than that of serology (both P<0.05). False positive and false negative results where found when the diagnosis of compensated liver cirrhosis was made by ultrasonography. CONCLUSION: There are different ultrasonographic predictors for the evaluation of hepatic inflammation grade and fibrosis stage of chronic hepatitis. Both ultrasonography and serology have their own advantages and disadvantages in the evaluation of liver fibrosis and compensated liver cirrhosis. Combined application of the two methods is hopeful to improve the diagnostic accuracy.     

Expression of Bcl-2 and Bax in extrahepatic biliary tract carcinoma and dysplasia

AIM: To compare the difference of expression of Bcl-2 and Bax in extrahepatic biliary tract carcinoma and dysplasia, and to analyze the role of Bcl-2 and Bax proteins in the progression from dysplasia to carcinoma and to evaluate the correlation of Bcl-2/Bax protein expression with the biological behaviors. METHODS: Expressions of Bcl-2 and Bax were examined immunohistochemically in 27 cases of extrahepatic biliary tract carcinomas (bile duct carcinoma: n=21, carcinoma of ampulla of Vater: n=6), and 10 cases of atypical dysplasia. Five cases of normal biliary epithelial tissues were used as controls. A semiquantitative scoring system was used to assess the Bcl-2 and Bax reactivity. RESULTS: The expression of Bcl-2 was observed in 10 out of 27 (37.0%) invasive carcinomas, 1 out of 10 dysplasias, none out of 5 normal epithelial tissues. Bax expression rate was 74.1% (20/27) in invasive carcinoma, 30% (3/10) in dysplasia, and 40% (2/5) in normal biliary epithelium. Bcl-2 and Bax activities were more intense in carcinoma than in dysplasia, with no significant difference in Bcl-2 expression (P=0.110), and significant difference in Bax expression (P=0.038). Level of Bax expression was higher in invasive carcinoma than in dysplasia and normal tissue (P=0.012). Bcl-2 expression was correlated to Bax expression (P=0.0059). However, Bcl-2/Bax expression had no correlation with histological subtype, grade of differentiation, or level of invasion. CONCLUSION: Increased Bcl-2/Bax expression from dysplasia to invasive tumors supports the view that this is the usual route for the development of extrahepatic biliary tract carcinoma. Bcl-2/Bax may be involved, at least in part, in the apoptotic activity in extrahepatic biliary carcinoma.