Plasmid DNA encoding transforming growth factor-beta1 suppresses chronic disease in a streptococcal cell wall-induced arthritis model.

Transforming growth factor beta is a potent immunomodulator with both pro- and antiinflammatory activities. Based on its immunosuppressive actions, exogenous TGF-beta has been shown to inhibit autoimmune and chronic inflammatory diseases. To further explore the potential therapeutic role of TGF-beta, we administered a plasmid DNA encoding human TGF-beta1 intramuscularly to rats with streptococcal cell wall-induced arthritis. A single dose of 300 microg plasmid DNA encoding TGF-beta1, but not vector DNA, administered at the peak of the acute phase profoundly suppressed the subsequent evolution of chronic erosive disease typified by disabling joint swelling and deformity (articular index = 8.17+/-0. 17 vs. 1.25+/-0.76, n = 6, day 26, P < 0.01). Moreover, delivery of the TGF-beta1 DNA even as the chronic phase commenced virtually eliminated subsequent inflammation and arthritis. Both radiologic and histopathologic as well as molecular evidence supported the marked inhibitory effect of TGF-beta1 DNA on synovial pathology, with decreases in the inflammatory cell infiltration, pannus formation, cartilage and bone destruction, and the expression of proinflammatory cytokines that characterize this model. Increases in TGF-beta1 protein were detected in the circulation of TGF-beta1 DNA-treated animals, consistent with the observed therapeutic effects being TGF-beta1 dependent. These observations provide the first evidence that gene transfer of plasmid DNA encoding TGF-beta1 provides a mechanism to deliver this potent cytokine that effectively suppresses ongoing inflammatory pathology in arthritis.     

筛检对肝癌死亡率影响的研究

5581名HBsAg阳性的男性随机分入周期性筛检组(A组,3712人)及对照组(B组,1869人)。A组(19155.4人年)共发生肝癌257例,B组(9785.5人年)为117例,两组的肝癌发生率分别为1342/10万与1196/10万;两组肝癌死亡分别为218与109例,肝癌死亡率分别为1138/10万与1114/10万。两组中Ⅰ期肝癌病例分别为29.6％与6.0％,差异有非常显著性意义。1、3、5年相对生存率A组为23.7％、7.0％、4.0％,B组为9.7％、4.0％、4.1％。用Poisson回归模型拟合显示,在调正年龄、初筛AFP及入列年份后,筛检对于肝癌的相对危险度为0.83,95％CI为0.68～1.03,有较弱的“保护”作用,Cox回归模型拟合结果显示当临床分期未引入模型时,筛检对于肝癌有显著的“保护”作用:危险率为0.6617,95％CI为0.5234～0.8365;而模型经调整后,危险率即接近“1”,95％CI为0.74～1.26。     

FM sonography in diffuse liver disease: prospective assessment and blinded analysis

FM sonography - a signal-processing technique that uses frequency and phase information as well as amplitude data - shows promise in evaluation of patients with diffuse liver disease. In a prospective blinded review of 37 patients with biopsy-proved liver disease and 42 healthy volunteers, FM sonography was clearly superior to traditional amplitude-based (AM) sonography in distinguishing healthy from diseased subjects. Statistically significant differences were seen in accuracy (FM, 98.7%; AM, 84.8%), sensitivity (FM, 97.3%; AM, 70.3%), and negative predictive value (FM, 97.7%; AM, 78.8%). Our data also suggest that current FM sonographic techniques cannot differentiate among histologic findings associated with different hepatic parenchymal abnormalities. It is unclear, therefore, whether FM imaging can reduce the numbers of patients who require biopsy for diagnosis or the frequency of biopsy procedures in patients with known disease.