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。     

Role for interleukin-1 (IL-1) in benzene-induced hematotoxicity: inhibition of conversion of pre-IL-1 alpha to mature cytokine in murine macrophages by hydroquinone and prevention of benzene-induced hematotoxicity in mice by IL-1 alpha

Chronic exposure of humans to benzene (BZ), a myelotoxin, causes aplastic anemia and acute leukemia. The stromal macrophage that produces interleukin-1 (IL-1), a cytokine essential for hematopoiesis, is a target of BZ's toxicity. Monocyte dysfunction and decreased IL-1 production have been shown to be involved in aplastic anemia in humans. Hydroquinone (HQ), a toxic bone marrow (BM) metabolite of BZ, causes time- and concentration-dependent inhibition of processing of the 34-Kd pre-interleukin-1 alpha (IL-1 alpha) to the 17-Kd mature cytokine in murine P388D1 macrophages and BM stromal macrophages, as measured by Western immunoblots of cell lysate proteins using a polyclonal rabbit antimurine IL-1 alpha antibody. HQ over a 10-fold concentration range had no effect on the lipopolysaccharide (LPS)-induced production of pre- IL-1 alpha precursor or on cell viability or DNA and protein synthesis. Stromal macrophages obtained from the femoral BM of C57Bl/6 mice exposed to BZ (600 or 800 mg/kg body weight) for 2 days were incapable of processing the 34-Kd pre-IL-1 alpha to the mature 17-Kd cytokine when stimulated in culture with LPS. Stromal macrophages from mice coadministered BZ and indomethacin, a prostaglandin H synthase (PHS) inhibitor that has been shown to prevent BZ-induced myelotoxic and genotoxic effects in mice when coadministered with benzene were able to convert the pre-IL-1 alpha to mature cytokine. Administration of recombinant murine IL-1 alpha (rMuIL-1 alpha) to mice before a dose of BZ that causes severe depression of BM cellularity completely prevents BM depression, most probably by bypassing the inability of the stromal macrophage in BZ-treated animals to process pre-IL-1 alpha to the mature cytokine.