过氧化体增殖物激活型受体γ对巨噬细胞脂质蓄积及CD36表达的影响

目的观察过氧化体增殖物激活型受体γ激动剂和拮抗剂对THP-1巨噬细胞胆固醇蓄积及CD36表达的影响。方法实验分对照组、氧化型低密度脂蛋白组、Ciglitazone处理组和GW9662处理组,后两组用50 mg/L氧化型低密度脂蛋白分别与过氧化体增殖物激活型受体γ激动剂Ciglitazone(10μmol/L)及拮抗剂GW9662(10μmol/L)共同孵育24 h,高效液相色谱分析法检测细胞总胆固醇蓄积情况,RT-PCR和Western blot分别检测THP-1巨噬细胞CD36 mRNA和蛋白的表达。结果与对照组(76.28±10.36 mg/g)相比,氧化型低密度脂蛋白(121.63±13.32 mg/g)能使细胞总胆固醇含量显著增加,而Ciglitazone能使氧化型低密度脂蛋白处理的细胞总胆固醇含量进一步增加(136.23±14.78 mg/g),GW9662能使氧化型低密度脂蛋白处理的细胞总胆固醇含量减少(98.52±11.45 mg/g)。过氧化体增殖物激活型受体γ拮抗剂GW9662使巨噬细胞CD36 mRNA和蛋白的表达下调及胆固醇蓄积减少,过氧化体增殖物激活型受体γ激动剂Ciglitazone使巨噬细胞CD36 mRNA和蛋白的表达上调及胆固醇蓄积增多。结论过氧化体增殖物激活型受体γ拮抗剂使THP-1巨噬细胞胆固醇蓄积减少及氧化型低密度脂蛋白诱导的CD36表达下调。     

芍药汤加味联合奥沙拉秦钠治疗湿热内蕴型活动期溃疡性结肠炎对照研究

[目的]观察芍药汤加味联合奥沙拉秦钠治疗湿热内蕴型活动期溃疡性结肠炎疗效。[方法]将40例门诊患者随机数字表法分为两组。对照组20例奥沙拉秦钠1g/次,2次/d,饭后口服。治疗组20例奥沙拉秦钠治疗同时加用芍药汤加味(白芍20g,黄芩15g,黄连9g,黄柏15g,大黄3g,槟榔9g,当归12g,木香12g,肉桂3g,甘草6g)1剂/d。均治疗6周,随访12月判定疗效。[结果]治疗组完全缓解12例,有效8例,无效0例,总有效率100.00%。对照组完全缓解10例,有效7例,无效3例,总有效率85.00%。临床疗效治疗组优于对照组(P<0.05),主要症状及结肠镜检有效率治疗组优于对照组(P<0.05)。[结论]芍药汤加味联合奥沙拉秦钠治疗湿热内蕴型活动期溃疡性结肠炎疗效优于单用奥沙拉秦钠,值得推广。     

一级并行米氏消除药物的稳态特性与给药方法

对非线性过程按一级并行米氏消除的药物，先给出ｎ次静脉推注药物浓度的解析表达式；然后进一步研究多剂给药的稳态特性，给出了稳态药物浓度、最高坪水平、最低坪水平、平均稳态浓度、达坪分数和积累系数等的解析表达式；并讨论了它们在制定最佳用药方案中的应用。     

Pathologic alterations in adult rainbow trout, Oncorhynchus mykiss, exposed to dietary 2,3,7,8-tetrachlorodibenzo-p-dioxin

Adult female rainbow trout (Oncorhynchus mykiss) fed [³H]2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) impregnated diet at 0, 1.8, 18 or 90 ng/kg food for up to 320 days were evaluated by clinical pathology, gross pathology and histopathology procedures. Gross pathological changes were limited to a slight increase in the incidence of lesions of the caudal fins in the treated groups. Mixed mononuclear inflammatory infiltrates were present in multiple organs of fish from control and treatment groups, but did not appear to be treatment related. Lesions associated with exposure to TCDD were observed histologically in liver and spleen after 100 and 250+ days of exposure. The livers of TCDD-treated fish contained less hepatocellular glycogen, more mitotic figures, greater anisokaryosis, anisocytosis, nuclear chromatin clumping and margination. Prominent nucleoli were directly proportional to TCDD dose. Hepatocellular changes in fish exposed to TCDD also included single cell necrosis and clear cytoplasmic vacuoles consistent with lipid. Some fish from all TCD exposed groups had lower lymphoid density compared to controls at all time intervals. Fish exposed to the highest TCDD dose had decreased peripheral leukocyte counts after 50 and 100 days. The lowest observable adverse effect level (LOAEL) for these effects was 5.69 ngTCDD/kg in diet and 0.90 ng TCDD/kg liver.     

结肠癌组织中微小RNA分子组学分析

目的 检测结肠癌组织与癌旁组织中微小RNA（miRNA）的差异表达.方法 采用实时荧光定量PCR法检测20例结肠癌组织与癌旁组织miRNA分子的差异表达,筛选具有显著差异表达（变化倍数大于2.4且P＜0.01）的miRNA,进一步通过聚类分析不同miRNA之间的聚集性.并分析miRNA与其他结肠癌相关蛋白表达的相关性.结果 17个miRNA分子在结肠癌组织中显著下调.聚类分析显示,其中miR763-3、miR451和miR99a表达相近.血浆CK20水平与miR100（r=-0.948）、miR125a-5p（r=-0.948）、miR125b（r=-0.949）、miR145 （r=-0.949）和miR145＊ （r=-0.949）均呈高度负相关（均P＜0.05）.结论 miR145等17种miRNA可作为结直肠诊断的分子标记物;miR100、miR125a-5p、miR125b、miR145和miR145＊可能成为提示结肠癌淋巴转移的分子标志物。     

Prolonged accumulation of high-dose methotrexate in a case with large liver cysts

Methotrexate (MTX) has been documented to accumulate in “third spaces’’ such as pleural effusions or ascitic fluids, resulting in delayed clearance and severe toxicity. We present a case of Burkitt lymphoma possessing large liver cysts, up to the size of 7 × 7 cm, wherein clearance of high-dose MTX was severely delayed, despite normal renal and liver functions. The serum MTX concentration was higher than 0.1 μM on day 12 and remained at toxic levels, higher than 0.01 μM, even on day 25, resulting in severe neutropenia, anorexia, and diarrhea. It was presumed that MTX accumulated in the liver cysts over time and was slowly released back into the serum, resulting into prolonged high serum MTX concentrations. High dose of MTX in patients with large liver cysts induces severe toxicity by virtue of MTX accumulation in the cysts and its subsequent delayed clearance.     

Anatomical distribution of diarrhetic shellfish poisoning (DSP) toxins in the mussel Mytilus galloprovincialis

The aim of this work was to shed light on the anatomical distribution of diarrhetic shellfish poisoning (DSP) toxins in the mussel Mytilus galloprovincialis and to determine any possible changes undergone during the depuration process. To this end, the distribution of two DSP toxins—okadaic acid and DTX2—and some of their derivatives were studied by means of HPLC/MS at different stages of the depuration process. Mussels were collected from mussel farms located in the Galician Rías and they were collected under three types of circumstances: (a) while ingesting toxic phytoplankton cells; (b) 1 week after the toxic cells had disappeared from the water; and (c) after ca. 2 months of depuration. Additionally, in case (b), the distribution among tissues was checked every week over a depuration period of 35 days in the laboratory. DSP toxins were only detected in non-visceral tissues when the extracts were concentrated 20-fold and, even in these cases, the concentrations found were very low. When the maximum possible contribution of non-visceral tissues was computed, taking into account the technique's detection limits and tissue weight, no relevant contribution to the toxin burden of non-visceral tissues was found at any stage of depuration, with the maximum possible contributions usually below 7%. The concentrated samples analysed showed that the actual contribution in all the cases studied was, in fact, less than 1% of the total toxin burden. These findings suggest that (1) when analytical methods are used to monitor DSP toxic mussels, non-visceral tissues should be assumed to be free of toxins in order to precisely compute the toxin concentration of the whole mass of edible tissues and (2) when studying the accumulation kinetics of DSP toxins, transference from the digestive gland to other tissues should not be taken into account, as the other tissues do not contain relevant amounts of DSP toxins.