I型内皮素受体反义寡聚核苷酸抑制VSMC增殖及内膜增生

目的　观察 型内皮素受体 (ETA)反义寡核苷酸(ODN)对血管平滑肌细胞 (VSMC)增殖和内膜增生的抑制作用 .方法　 1细胞培养 :取家兔主动脉中膜消化后培养传代 ,经抗 α- actin鉴定后使用第 4～ 6代传代细胞 ;2人工合成ODN:经 Genbank检索筛选 ,合成含 18bp ETA- ODN片段 ,再对 5 端硫代修饰以增加稳定性 ,同时行地高辛标记以检测反义片段的细胞膜穿透性 ;3 MTT分光光度法检测 ETA-ODN对 VSMC增殖的抑制作用 ;4运用放射受体结合分析法 (1 2 5I- ET- 1)了解 ODN对 ETA蛋白表达的抑制作用 ,以探讨其反义作用 ;5兔颈动脉空气干燥模型在体研究 ODN对血管内膜增生的抑制作用 :应用 F- 12 7凝胶载体携带 ETA-ODN(3.0μmol· L- 1 )导入血管周围 ,术后不同时间观察增生内膜相对厚度 .结果　 ODN于培养后 12 h进入细胞内 ,并逐渐增加 ;15 μmol· L- 1 ETA- ODN对 VSMC增殖具有抑制作用 ,2 4h后即有显著作用 ;ETA- ODN对 ETA表达亦有明显的抑制作用 ,表现为 CPM于 2 4h逐渐减少 ;ETA- ODN导入后 ,血管增生内膜相对厚度减少 .结论　 ETA- ODN以浓度和时间依赖方式抑制 ETA蛋白表达以及 VSMC的增殖 ;反义寡核苷酸是通过反义机制实现对 ETA蛋白和 VSMC增殖的抑制作用     

前列腺癌肿瘤血管生成的研究

目的：探讨肿瘤微血管与前列腺癌生长,转移的关系。方法：应用免疫组化技术结合放射免疫测定检测第Ⅷ因子相关抗原和前列腺特异性抗原（PSA）在19例前列腺癌和40例前列腺增生中的表达和平均值及其相关关系。结果：前列腺癌组织中微血管密度（MVD）和PSA值明显高于前列腺增生,转移性前列腺癌MVD和PSA值高于非转移性前列腺癌,前列腺癌MVD与PSA呈正相关,结论：血管形成与前列腺癌的发生,发展和转移密切相关,肿瘤的增长和转移有赖于肿瘤血管的生成。     

职业性慢性放射病临床诊断及预后

目的：探讨慢性放射病（以下简称慢放病）的诊断、治疗及预后。方法：以受照剂量,临床症状,造血功能,Ｔ淋巴细胞百分率,染色体畸变率对３０例慢性放射损伤患者进行综合分析判断,对其中１１例慢放病用胸腺肽治疗并追踪观察１０年。结果：慢放病患者受照剂量超过２Ｓｖ,白细胞下降伴有几髓造血功能障碍,Ｔ淋巴细胞百分率下降,染色体畸变率显著上升。胸腺肽能改善临床症状,显著提高细胞免疫功能。慢放病各项指标恢复依时间顺序为：Ｔ淋巴细胞百分率（２年）,临床症状（３．５年）,造血功能（５～８年）,染色体畸变率（１０年）。结论：受照剂量是误断慢放病的重要依据;白细胞总数、骨髓造血功能改变是诊断的关键;Ｔ淋巴细胞百分率、染色体畸变率可作为鉴别诊断指标。慢放病是一种可以恢复的职业性疾病,胸腺肽治疗有助于慢放病的恢复。     

Risk factors for hepatocellular carcinoma at baseline and 1 year after initiation of nucleos(t)ide analog therapy for chronic hepatitis B

Nucleos(t)ide analogs (NAs) cannot completely suppress the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). This study aimed to identify the risk factors for HCC development in naïve CHB patients treated with current NA. Patients receiving NA (n = 905) were recruited retrospectively from the 17 hospitals of the Japanese Red Cross Liver Study Group. All treatment-naïve patients had been receiving current NA continuously for more than 1 year until the end of the follow-up. We analyzed the accuracy of predictive risk score using the area under receiver operating characteristic curve. The albumin–bilirubin (ALBI) score was significantly improved by NA therapy (−0.171 ± 0.396; p < 0.001 at Week 48). A total of 72 (8.0%) patients developed HCC over a median follow-up of 6.2 (1.03–15.7) years. An independent predictive factor of HCC development was older age, cirrhosis, lower platelet counts at baseline and ALBI score, and alpha-fetoprotein (AFP) at 1 year after NA therapy according to multivariate analysis. The accuracy was assessed using the PAGE-B, mPAGE-B, aMAP, APA-B, and REAL-B scores that included these factors. Discrimination was generally acceptable for these models. aMAP and REAL-B demonstrated high discrimination with 0.866/0.862 and 0.833/0.859 for 3- and 5-year prediction from the status of 1 year after NA therapy, respectively. Baseline age and platelet count, as well as ALBI and AFP one year after NA, were useful for stratifying carcinogenesis risk. The aMAP and REAL-B scores were validated with high accuracy in Japanese CHB patients.     

Bone scan of hemodialysis patients with secondary hyperparathyroidism before and after parathyroidectomy

Renal osteodystrophy (ROD) accompanied by long-term hemodialysis patients with chronic renal failure includes several forms of disorders of mineral and skeletal metabolism such as osteitis fibrosa attributed to secondary hyperparathyroidism, osteomalasia and adynamic bone disease. Bone scan is performed to detect of the mainly pathophysiology of ROD. We investigated bone scan of 25 hemodialysis patients with secondary hyperparathyroidism diagnosed clinically before and after parathyroidectomy (PTX). Before PTX an diffusely high accumulation of bone seeking agent in the whole skeleton especially skull in all patients (100%), vertebra in 24 out of 25 (96%), patella in 24/25 (96%), limbs in 23/25 (92%), sternum in 19/25 (76%), sacrum in 18/25 (72%) and costochondral junctions in 14/25 (56%) was noted in these patients. The radionuclide activity of the calvaria, maxilla and mandible in the skull was prominently high. Fourteen patients had an equally high activity in the calvaria, maxilla and mandible, 6 patients had higher activity in the maxilla and mandible than that of calvaria and 5 patients had higher in the calvaria than that of maxilla and mandible. After PTX the changes in the skull were obvious in 19 patients who showed a more markedly decreased in activity of the maxilla and mandible than that of the calvaria. In 3 patients showed a more markedly decreased in activity of the calvaria than that of the maxilla and mandible. Another 3 demonstrated equally decreased in activity in the calvaria, maxilla and mandible. It became clear that the highest activity of the skull was shown in all patients and the therapeutic changes of the skull are the most pronounced in maxilla and mandible in this study.     

Manometric Evidence of Improved Early Gastric Stasis by Erythromycin after Pylorus-preserving Pancreatoduodenectomy

Gastric stasis is a frequent complication of pylorus-preserving pancreatoduodenectomy (PPPD). We demonstrated that it might be attributable to delayed recovery of phase III activity of the gastric migrating motor complex due to low concentrations of plasma motilin caused by resection of the duodenum. Leucine 13-motilin is effective for treating gastric stasis, but it is not yet available for clinical use. Whether erythromycin would improve early gastric stasis after PPPD was tested clinically and by manometry. A manometric tube assembly and a gastrostomy tube were inserted in the stomach of 10 patients at PPPD for pressure recording from the gastric antrum and jejunum and for gastric juice drainage, respectively. After baseline recording, erythromycin 5 mg/kg was given intravenously on day 14 and saline as a placebo on day 17 every 4 hours four times a day. The daily volume of gastric juice output and the gastric motility index were measured. The mean period until the return of gastric phase III was 31 +/- 1 days. Erythromycin significantly increased the gastric motility index from 7.9 +/- 1.3 mmHg to 15.7 +/- 1.8 mmHg (p = 0.0005), whereas saline did not (7.2 +/- 1.6 mmHg to 6.5 +/- 1.2 mmHg; p = 0.21). Erythromycin significantly decreased the gastric juice output from 1,080 +/- 190 ml to 738 +/- 199 ml (p < 0.0001), but the saline injections did not (1,064 +/- 174 ml to 1,115 +/- 189 ml; p = 0.35). Erythromycin, a universally available motilin agonist, is a safe, effective, potent drug for the treatment of early gastric stasis after PPPD.     

聚乙二醇修饰水蛭素的分离纯化与活性分析

用活化的聚乙二醇(PEG)对水蛭素进行化学修饰，质谱分析表明，修饰产物是修饰度不同的分子质量相差5000u的水蛭素的混合物。用离子交换层析和凝胶过滤层析对反应产物进行分离纯化，离子交换层析难以达到完全分离；而采用凝胶过滤层析方法可较好地分离修饰度不同的各组份。生物学活性分析表明，不同的PEG修饰度对水蛭素的活性具有显著影响，连接1～2个PEG的水蛭素保持了原有活性，而连接3个PEG的水蛭素活性显著下降。     

辛伐他汀治疗老年人高脂血症的临床观察

目的 :了解辛伐他汀 (舒降之 )治疗老年人高脂血症的疗效。方法 :对 93例老年高脂血症患者采用舒降之治疗。结果 :治疗了 4周和 8周后 ,胆固醇 (TC)明显降低 2 2 %、2 7% (P <0 .0 1) ,低密度脂蛋白 (LDL C)明显降低 17%、2 4 % (P <0 .0 1) ,高密度脂蛋白 (HDL C)增加 15 %、16 % (P <0 .0 5 ) ,三酰甘油 (TG)降低 18%、2 1% (P <0 .0 5 ) ,仅有轻微不良反应。结论 :辛伐他汀可显著降低TC、LDL C ,可中等程度降低TG及升高HDL C。表明辛伐他汀是治疗老年人高脂血症的理想调脂药物