药用矿物蒙脱石的X-射线定向衍射分析

目的：揭示蒙脱石层状晶体结构及层间吸附和膨胀性能,为其作为药物和药剂辅料提供科学依据。方法：将样品提纯,获得粒径小于1μm的胶体,制成取向样品,进行X－射线定向衍射分析。结果：得到了有关蒙脱石层间域在不同条件下的变化规律。结论：蒙脱石的层间吸附是可能的,而且定向衍射方法可以定量测定其层间距离。     

石油沥青对职业人群健康影响的调查

目的调查长期接触石油沥青对职业人群健康的影响，为制订职业卫生标准提供职业流行病学调查资料。方法对防水材料生产企业和石油沥青暴露人群进行作业场所劳动卫生学和职业流行病学调查。结果对石油沥青暴露组394人，对照组237人调查结果表明，暴露组失眠、胸闷、鼻干等症状出现率高于对照组，其他检查显示，暴露组肺纹理增强、支气管炎出现率虽高于对照组，但无统计学意义。结论作业场所石油沥青烟浓度为0．69—10．46mg／m^3的情况下，石油沥青对职业人群健康没有产生明显的损害作用，也没有发现特异性损害。     

金属硫蛋白和肿瘤增殖抗原在肾癌组织中的表达及意义

目的　探讨金属硫蛋白 (MT)和肿瘤增殖抗原 (Ki 67)在肾癌组织中的表达及意义。　方法　应用免疫组化SABC法检测 5 9例肾癌患者组织标本及 19例正常肾组织标本中MT及Ki 67蛋白表达 ,流式细胞术检测DNA含量及S期比例。　结果　MT在肾癌及正常肾组织中的阳性表达率分别为 5 2 .5 %和 78.9% (P <0 .0 5 ) ;G1表达率高于G2 、G3(P <0 .0 1) ,Ⅰ、Ⅱ期高于Ⅲ、Ⅳ期 (P <0 .0 5 ) ,有无淋巴结转移之间差别有显著性意义 (P <0 .0 1) ,不同直径肿瘤之间差别无显著性意义 (P>0 .0 5 )。MT( )及MT( - )患者术后 5年生存率分别为 5 8.1%和 2 8.6% (P <0 .0 5 )。肾癌组织Ki 67指数高于正常肾组织 (P <0 .0 1) ,且与病理分级、临床分期相关 ;Ki 67指数较高者 ,MT表达率较低 ,MT表达率及Ki 67指数分别与S期比例显著相关。　结论　MT及Ki 67蛋白可能参与肾癌的发生、进展及转移过程 ,可作为肾癌细胞增殖及预后估计的参考指标。     

Mpl受体介导的HEL细胞电子传递反应的变化

为研究Mpl受体介导的HEL细胞电子传递反应的变化,建立了用细胞电极测定HEL细胞电子传递的电化学方法。结果发现,当TPO-Mpl作用后数分钟可以观察到一个向上的“”形氧化电位,TPO-Mpl的最大作用出现在5分钟内,TPO-Mpl的解离在二者作用后60分钟趋向明显,240分钟后完全解离。Scatchard分析说明HEL细胞表面有两种Mpl受体亲和力(K_1=1.8 pmol/L,K_2=1.11nmol/L)。结果提示,TPO与Mpl受体结合迅速,解离缓慢,HEL细胞上存在两种亲和力的Mpl受体。该方法灵敏、方便,可以连续观察,需要细胞少(1.0×10~4细胞)。     

Our Postpandemic World: What Will It Take to Build a Better Future for People and Planet?

Policy Points

• Despite the pandemic''s ongoing devastating impacts, it also offers the opportunity and lessons for building a better, fairer, and sustainable world.
• Transformational change will require new ways of working, challenging powerful individuals and industries who worsened the crisis, will act to exploit it for personal gain, and will work to ensure that the future aligns with their interests.
• A flourishing world needs strong and equitable structures and systems, including strengthened democratic, research, and educational institutions, supported by ideas and discourses that are free of opaque and conflicted influence and that challenge the status quo and inequitable distribution of power.

     

DMPK dosage alterations result in atrioventricular conduction abnormalities in a mouse myotonic dystrophy model

Myotonic dystrophy (DM) is the most common form of muscular dystrophy and is caused by expansion of a CTG trinucleotide repeat on human chromosome 19. Patients with DM develop atrioventricular conduction disturbances, the principal cardiac manifestation of this disease. The etiology of the pathophysiological changes observed in DM has yet to be resolved. Haploinsufficiency of myotonic dystrophy protein kinase (DMPK), DM locus-associated homeodomain protein (DMAHP) and/or titration of RNA-binding proteins by expanded CUG sequences have been hypothesized to underlie the multi-system defects observed in DM. Using an in vivo murine electrophysiology study, we show that cardiac conduction is exquisitely sensitive to DMPK gene dosage. DMPK-/- mice develop cardiac conduction defects which include first-, second-, and third-degree atrioventricular (A-V) block. Our results demonstrate that the A-V node and the His-Purkinje regions of the conduction system are specifically compromised by DMPK loss. Importantly, DMPK+/- mice develop first-degree heart block, a conduction defect strikingly similar to that observed in DM patients. These results demonstrate that DMPK dosage is a critical element modulating cardiac conduction integrity and conclusively link haploinsufficiency of DMPK with cardiac disease in myotonic dystrophy.     

Cytoplasmic CUG RNA Foci Are Insufficient to Elicit Key DM1 Features

The genetic basis of myotonic dystrophy type I (DM1) is the expansion of a CTG tract located in the 3′ untranslated region of DMPK. Expression of mutant RNAs encoding expanded CUG repeats plays a central role in the development of cardiac disease in DM1. Expanded CUG tracts form both nuclear and cytoplasmic aggregates, yet the relative significance of such aggregates in eliciting DM1 pathology is unclear. To test the pathophysiology of CUG repeat encoding RNAs, we developed and analyzed mice with cardiac-specific expression of a beta-galactosidase cassette in which a (CTG)₄₀₀ repeat tract was positioned 3′ of the termination codon and 5′ of the bovine growth hormone polyadenylation signal. In these animals CUG aggregates form exclusively in the cytoplasm of cardiac cells. A key pathological consequence of expanded CUG repeat RNA expression in DM1 is aberrant RNA splicing. Abnormal splicing results from the functional inactivation of MBNL1, which is hypothesized to occur due to MBNL1 sequestration in CUG foci or from elevated levels of CUG-BP1. We therefore tested the ability of cytoplasmic CUG foci to elicit these changes. Aggregation of CUG RNAs within the cytoplasm results both in Mbnl1 sequestration and in approximately a two fold increase in both nuclear and cytoplasmic Cug-bp1 levels. Significantly, despite these changes RNA splice defects were not observed and functional analysis revealed only subtle cardiac dysfunction, characterized by conduction defects that primarily manifest under anesthesia. Using a human myoblast culture system we show that this transgene, when expressed at similar levels to a second transgene, which encodes expanded CTG tracts and facilitates both nuclear focus formation and aberrant splicing, does not elicit aberrant splicing. Thus the lack of toxicity of cytoplasmic CUG foci does not appear to be a consequence of low expression levels. Our results therefore demonstrate that the cellular location of CUG RNA aggregates is an important variable that influences toxicity and support the hypothesis that small molecules that increase the rate of transport of the mutant DMPK RNA from the nucleus into the cytoplasm may significantly improve DM1 pathology.