p53抑制剂pifithrin-α对肝原代细胞增殖的影响

目的:观察p53抑制剂pifithrin-α对肝原代细胞增殖及增殖相关蛋白表达的影响。方法:肝原代细胞分别经0、10、20和30μmol/L的pifithrin-α处理1h后,再用10nmol/LEGF诱导30、36和48h,用放射性计数法测定细胞增殖水平。另取肝原代细胞,分3组,对照组常规培养,EGF组用10nmol/L的EGF诱导,EGF+pifithrin-α组用30μmol/Lpifithrin-α和10nmol/LEGF诱导,EGF诱导24、30h后,Westernblot法检测细胞中P53、P21、CyclinD、CyclinE、pErk蛋白的表达水平。结果:pifithrin-α作用后,EGF诱导的细胞增殖水平均降低,且pifithrin-α浓度越大,增殖水平越低(F剂量=54.690,F时间=214.370,F交互=50.450,P<0.001)。与对照组比较,EGF组细胞P53、Cyc-linE蛋白表达水平未发生变化,但P21、CyclinD及pErk表达水平升高(P<0.05),EGF+pifithrin-α组细胞P21、CyclinD及pErk蛋白表达水平较EGF组降低(P<0.05)。结论:P53蛋白可能通过激活MAPK信号通路、上调Cy-clinD表达,从而发挥促进肝原代细胞增殖的作用。     

Hepatoprotective effect of chitosan-caffeic acid conjugate against ethanol-treated mice

The chitosan-caffeic acid (CCA) conjugate shows a hepatoprotective effect against oxidative stress-induced hepatic damage in cultured hepatocytes. The objective of this study is the verification of the hepatoprotective effect of the CCA in vivo against ethanol-induced liver injury in mice. The administration of ethanol resulted in the increase of the serum-aminotransferase activities (AST and ALT), triglycerides, total cholesterol, and lipid peroxidation. The CCA co-administration, however, significantly (p < 0.05) ameliorated these serum biomarkers. The antioxidant-enzyme activities in the liver tissue, including those of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), were significantly decreased by a chronic ethanol administration, whereas the hepatic lipid-peroxidation level was increased. Moreover, the chronic ethanol administration elevated the gene expression of pro-inflammatory cytokines such as tumor-necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in the liver tissue. The CCA co-administration, however, significantly (p < 0.05) increased the activities of the SOD, CAT, and GPx and caused the down-regulation of the TNF-α- and IL-6-gene expressions in the liver tissue. An histopathologic evaluation also supported the hepatoprotective effect of the CCA against ethanol-induced hepatotoxicity in the mice.     

Leg Weakness in a Patient with Lumbar Stenosis and Adrenal Insufficiency

Lumbar spinal stenosis (LSS) is a common spinal disease in the elderly. The cardinal symptom of LSS is neurogenic claudication, but not all patients present with such typical symptom. The clinical symptoms are often confused with symptoms of peripheral neuropathy, musculo-skeletal disease and other medical conditions in elderly patients. In particular, LSS presenting with rapid progression of leg weakness must be distinguished from other combined diseases. We report a case of rapid progressive leg weakness in a patient with LSS and iatrogenic adrenal insufficiency that was induced by obscure health supplement.     

Distribution of Mercury Concentrations in Tree Rings and Surface Soils Adjacent to a Phosphate Fertilizer Plant in Southern Korea

This study aimed to determine mercury concentrations in tree rings and surface soils at distances of 4, 26 and 40 km from a fertilizer plant located in Yeosu City, Korea. Mercury concentrations in all tree rings were low prior to the establishment of the plant in 1977 and became elevated thereafter. The highest average mercury concentration in the tree rings was 11.96 ng g^?1 at the Yeosu site located nearest to the plant, with the lowest average mercury concentration of 4.45 ng g^?1 at the Suncheon site furthest away from the plant. In addition, the highest mercury content in the surface soil was 108.51 ng cm^?3 at the Yeosu site, whereas the lowest mercury content in the surface soil was 31.47 ng cm^?3 at the Suncheon site. The mercury levels decreased gradually with increasing distance from the plant.     

Addressing Methodologic Challenges and Minimizing Threats to Validity in Synthesizing Findings from Individual-Level Data Across Longitudinal Randomized Trials

Integrative Data Analysis (IDA) encompasses a collection of methods for data synthesis that pools participant-level data across multiple studies. Compared with single-study analyses, IDA provides larger sample sizes, better representation of participant characteristics, and often increased statistical power. Many of the methods currently available for IDA have focused on examining developmental changes using longitudinal observational studies employing different measures across time and study. However, IDA can also be useful in synthesizing across multiple randomized clinical trials to improve our understanding of the comprehensive effectiveness of interventions, as well as mediators and moderators of those effects. The pooling of data from randomized clinical trials presents a number of methodological challenges, and we discuss ways to examine potential threats to internal and external validity. Using as an illustration a synthesis of 19 randomized clinical trials on the prevention of adolescent depression, we articulate IDA methods that can be used to minimize threats to internal validity, including (1) heterogeneity in the outcome measures across trials, (2) heterogeneity in the follow-up assessments across trials, (3) heterogeneity in the sample characteristics across trials, (4) heterogeneity in the comparison conditions across trials, and (5) heterogeneity in the impact trajectories. We also demonstrate a technique for minimizing threats to external validity in synthesis analysis that may result from non-availability of some trial datasets. The proposed methods rely heavily on latent variable modeling extensions of the latent growth curve model, as well as missing data procedures. The goal is to provide strategies for researchers considering IDA.