拉萨地区冠心病与幽门螺杆菌感染相关性研究

目的探讨西藏拉萨地区幽门螺杆菌（Helicobacter pyloric，Hp）感染与冠心病及多种危险因素的关系。为该地区冠心病的防治提供依据。方法分为冠心病组46例和非冠心病组51例，应用检测血抗HpIgG及-C-尿素呼气试验方法检测Hp感染情况，并分别测定各组血脂、血糖、餐后2h血糖、C反应蛋白、纤维蛋白原、白细胞总数。结果冠心病组患者血清抗HpIgG阳性率为50．0％（23／46），明显高于非冠心病组的23．5％（12／51），P〈0．05；冠心病患者Hp现症感染率为54．3％（25／46），明显高于非冠心病组的31．3％（27／51），P〈0．05；冠心病组Hp感染患者血脂、空腹及餐后2h血糖、C反应蛋白、纤维蛋白原较非感染患者明显升高（P〈0．05）。结论Hp感染与冠心病相关，可能是拉萨地区冠心病发病的独立危险因素。     

Comparative mouse skin tumorigenicity and induction of Ha-ras mutations by bay region diol epoxides of 5-methylchrysene and 5,6- dimethylchrysene

We compared the tumor-initiating activities toward mouse skin of two structurally related polycyclic aromatic hydrocarbon diol epoxides: racemic anti-1,2,3,4-tetrahydro-5,6-dimethylchrysene-1,2-diol-3,4- epoxide (5,6-diMeCDE) and racemic anti-1,2,3,4-tetrahydro-5- methylchrysene-1,2-diol-3,4-epoxide (5-MeCDE). Tumors induced by these diol epoxides were analysed for mutations in the Ha-ras gene. 5,6- diMeCDE is derived from the non-planar parent compound 5,6- dimethylchrysene, and reacts to approximately equal extents with dA and dG in DNA, whereas 5-MeCDE is derived from a nearly planar parent compound, 5-methylchrysene, and reacts mainly with dG in DNA. 5,6- diMeCDE, at initiating doses of 33, 100 or 400 nmol per mouse, induced 1.2, 2.2 and 6.2 skin tumors per mouse, respectively. It was significantly less tumorigenic than 5-MeCDE which induced 3.1, 7.5 and 9.1 skin tumors per mouse at the same doses. Tumors induced by 5,6- diMeCDE had a large number of CAA-->CTA mutations in codon 61 of the Ha- ras gene: 50, 55 and 75% of the tumors analysed had this mutation at the 33, 100 and 400 nmol doses. No mutations were found in codons 12 and 13 in the tumors induced by 5,6-diMeCDE. In contrast, CAA-->CTA mutations in codon 61 were rarely seen in tumors induced by 5-MeCDE. At the highest dose of 5-MeCDE, 20% of the tumors analysed had mutations at G of codons 12 and 13. The results of this comparative study support the hypothesis that mutations in the Ha-ras gene in mouse skin tumors induced by PAH diol epoxides occur as a result of their direct reaction with the gene. However, pathways other than the commonly observed Ha- ras codon 61 mutations are clearly important in mouse skin tumorigenesis by these diol epoxides.      

Paraoxonase1 deficiency in mice is associated with hypotension and increased levels of 5,6-epoxyeicosatrienoic acid

AimSerum paraoxonase 1 (PON1) is an HDL-associated lipolactonase and its association with hypertension is controversial. We studied the possible role of PON1 in blood pressure (BP) regulation, by using PON1 knockout (PON1KO) mice.Methods and resultsBoth, systolic and diastolic BPs were lower in PON1KO compared to WT mice. Hypotension detected in PON1KO is probably neither related to nitric oxide/guanylate cyclase-mediated vasodilation nor to angiotensin II or aldosterone-mediated vasoconstriction. Surprisingly, when challenged by high-salt diet, BP was further reduced in PON1KO mice. The later, pointed to a possible involvement of transient receptor potential vanilloid 4 (TRPV4), and indeed, administration of ruthenium red, a TRPV4 blocker, resulted in a sharp rise in BP. The protein levels of TRPV4 in kidneys of PON1KO were not higher than in WT. However, the renal level of 5,6-epoxyeicosatrienoic acid (5,6-EET), a TRPV4 specific agonist, was significantly higher in PON1KO compared with WT mice. 5,6-EET levels were further elevated under high-salt diet or administration of arachidonic acid. Injection of inhibitor of CYP450 epoxygenase resulted in increased BP in PON1KO mice. Injection of recombinant human PON1 resulted in elevation of BP and a concomitant reduction in renal content of 5,6-EET. PON1, in vitro, metabolized 5,6-EET, but not other EETs, to its corresponding diol. Vasodilation, blocked by excess of dietary K⁺ but not reversed by depletion of cellular Ca²⁺ stores, point to endothelial-derived hyperpolarization-like response.ConclusionThe present study shows causal, direct relationship between PON1 and blood pressure which is mediated, at least in part, by the regulation of 5,6-EET.     

Pulmonary hypertension in patients with end-stage renal disease

BACKGROUND: The aims of this study were to evaluate the incidence of unexplained pulmonary hypertension (PH) among patients with end-stage renal disease (ESRD) and to suggest possible etiologic factors. METHODS: The incidence of PH was prospectively estimated by Doppler echocardiography in 58 patients with ESRD receiving long-term hemodialysis via arteriovenous access, and in control groups of 5 patients receiving peritoneal dialysis (PD) and 12 predialysis patients without a known other cause to suggest the presence of PH. Clinical variables were compared between patients with and without PH receiving hemodialysis. Changes in pulmonary artery pressure (PAP) values before and after onset of hemodialysis via arteriovenous access, arteriovenous access compression, and successful kidney transplantation were recorded. RESULTS: PH > 35 mm Hg was found in 39.7% of patients receiving hemodialysis (mean +/- SD, 44 +/- 7 mm Hg; range, 37 to 65 mm Hg), in none of the patients receiving PD, and in 1 of 12 predialysis patients. Patients with PH receiving hemodialysis had a significantly higher cardiac output (6.9 L/min vs 5.5 L/min, p = 0.017). PH developed in four of six patients with normal PAP after onset of hemodialysis therapy via arteriovenous access. One-minute arteriovenous access compression in four patients decreased the mean systolic PAP from 52 +/- 7 to 41 +/- 4 mm Hg (p = 0.024). PH normalized in four of five patients receiving hemodialysis following kidney transplantation. Kaplan-Meier survival analysis according to PAP values revealed significant survival differences (p < 0.024). CONCLUSIONS: This study demonstrates a surprisingly high incidence of PH among patients with ESRD receiving long-term hemodialysis with surgical arteriovenous access. Both ESRD and long-term hemodialysis via arteriovenous access may be involved in the pathogenesis of PH by affecting pulmonary vascular resistance and cardiac output.     

2型糖尿病家系非糖尿病一级亲属胰岛素抵抗与胰岛β细胞功能变化5年随访研究

目的：探讨随访2型糖尿病（T2DM）家系非糖尿病一级亲属5年的胰岛素抵抗和胰岛β细胞功能变化。方法：入选2型糖尿病家系非糖尿病一级亲属组（FDR）32例和正常对照组（NC）18例,基线检测了体质量指数、腰臀比、血压、血脂、血糖和空腹胰岛素（FINS）水平。采用稳态模式（HOMA）评价胰岛素抵抗（HOMA-IR）和胰岛β细胞功能（HOMA-β）,5年后进行了相同的随访。结果：5年后FDR组HOMA-IR明显升高（P=0.040）,HOMA-β明显降低（P=0.004）。5年后FDR组与NC组HOMA-IR组间无显著差异（P=0.594）,HOMA-β明显降低（P=0.000）。多元逐步回归分析显示,FINS、空腹血糖（FBG）、高密度脂蛋白-胆固醇（HDL-C）是影响FDR组胰岛素抵抗的独立危险因素;FBG和FINS是影响FDR组胰岛β细胞功能的独立危险因素。结论：T2DM患者一级亲属非肥胖患者在发生糖尿病之前已经存在胰岛素抵抗和胰岛分泌功能缺陷,且随着病程延长胰岛β细胞功能衰竭可能更明显。     

肠镜在腹腔镜辅助低位直肠癌根治术后吻合口出血防治中的意义

目的:探讨肠镜在腹腔镜辅助低位直肠癌根治术后吻合口出血防治中的意义。方法 :回顾性分析我院2006年1月至2011年12月共279例腹腔镜直肠癌根治术病人的资料,其中18例术后吻合口出血。采用卡方检验分析影响吻合口出血的可能因素,对于P