Glucagon-like peptide-1 (GLP-1) is an incretin hormone that facilitates insulin secretion and preserves β cell function. hypertriglyceridemia plays an important role in the pathogenesis of insulin resistance and T2DM. The purpose of this study was to measure fasting active GLP-1 levels in hypertriglyceridemia subjects and analyse the relationship between GLP-1 and insulin resistance. We recruited 146 subjects including 38 diabetes patients with hypertriglyceridemia, 33 diabetes patients without hypertriglyceridemia, 35 hypertriglyceridemia subjects, and 40 healthy subjects as the normal control group. Serum fasting active GLP-1 was tested with ELISA in the four groups, and associations with insulin resistance were analysed. Serum fasting active GLP-1 levels were significantly increased in hypertriglyceridemia subjects with or without T2DM compared with healthy controls, particularly hypertriglyceridemia patients with T2DM (p < 0.01). GLP-1 levels positively correlated with triglyceride (TG) levels, fasting insulin (FINS) levels, and HOMA-IR (p < 0.01). Furthermore, multiple stepwise regression showed that TG levels and HOMA-IR were independently associated with fasting active GLP-1 levels (p < 0.01). Hypertriglyceridemia was associated with elevated fasting active GLP-1 levels, and a significant association was noted between GLP-1 and HOMA-IR. This finding provides evidence that the increase in GLP-1 may play a compensatory role in the pathogenesis of insulin resistance induced by hypertriglyceridemia.

Thyroid disease associated with abnormal lipid profile, which may lead to atherosclerosis. Although several observations indicate that serum Thyroid Stimulating Hormone (TSH) levels in the high normal range are related to Cardiovascular (CVD) risk factors in the general population. However, it remains to be elucidated that the association between thyroid hormones within the normal range and lipids in patients with type 2 diabetes. Thyroid hormones, TSH levels, antithyroid antibodies, anthropometric parameters, lipid profile, glucose and blood pressure were measured in 404 euthyroid new-onset type 2 diabetic subjects. Pearson’s correlation analysis and multiple linear regression analysis were used to assess the influence of thyroid function parameters on the lipid profiles. The result showed that Total Cholesterol (TC), Low Density Lipoprotein-Cholesterol (LDL-C), Apolipoprotein B (ApoB) and Apolipoprotein A1 (ApoA1) increased linearly with the elevation of TSH within the normal range. Multiple regression analysis demonstrated high normal TSH level was positively correlated with the TC, LDL-C, ApoA1 and ApoB, serum Free Thyroxine (FT4) level was negative correlated with TC, Triglyceride (TG) and ApoB. The change of thyroid function, even within reference range of thyroid function tests, high normal TSH and low FT4 might exert adverse effects on the lipid profile resulting in hypercholesterolemia and hypertriglyceridemia, two well-known CVD risk factors.

Background: Receptor tyrosine kinases (RTKs) play crucial roles in numerous cancer cell processes including cell survival, proliferation, and migration. MEK1/2 MAPK kinases are very important for cancer survival and development. Anaplastic thyroid carcinoma (ATC) is a deadly type of thyroid cancer and there are no very effective systemic treatment strategies for ATC so far. Also, ATC can easily become resistant to therapy of traditional therapeutic drugs for ATC, such as doxorubicin. Drug combination treatment could be a promising therapeutic strategy for ATC, especially for drug resistant ATC.Methods: We explored the combination effect between a MEK1/2 inhibitor SL327 and a multi-targeted RTK inhibitor Sunitinib Malate in doxorubicin resistant ATC cells using cell viability assay, cell migration assay, nuclei morphology and caspase-3 activity analysis, as well as in vivo tumor growth assay.Results: There is a significant additive effect between SL327 and Sunitinib Malate in reducing viability, increasing apoptosis, and suppressing migration of doxorubicin-resistant ATC cells. Importantly, combination of SL327 and Sunitinib Malate induced significant additive suppression of in vivo doxorubicin-resistant ATC tumor growth.Conclusions: Our results suggest that the combination of MEK1/2 inhibitor and RTK inhibitor is promising for treatment of ATC especially doxorubicin-resistant ATC. The combination might not only enhance the anti-cancer efficacy, but also reduce the side effects and overcome drug resistance developed in ATC treatment. All these might provide useful information for clinical therapeutics of ATC. (C) 2017 Elsevier Masson SAS. All rights reserved.

目的 分析与探讨血液透析患者进行中心静脉置管后发生导管相关血流感染的病原菌分布特点及相应的治疗措施.方法 选取2013-01 ～ 2016-12该院肾内科及血液净化科以中心静脉置管建立血管通路进行血液透析的患者400例,分析发生导管相关血流感染患者的临床资料、病原菌分布特点及药敏结果.结果 400例行中心静脉置管患者中,发生导管相关血流感染43例(10.75％).病原菌分布以革兰氏阳性菌为主,占感染总数的69.77％,其中18例金黄色葡萄球菌,12例表皮葡萄球菌,对利奈唑胺、万古霉素、替考拉宁等抗生素敏感率均很高.革兰氏阴性菌占感染总数的30.23％,包括10例大肠埃希氏杆菌,3例鲍曼不动菌,对亚胺培南及美洛培南等抗生素敏感性最高.发生感染的患者平均年龄较大,空腹血糖较高,同时伴有贫血及低蛋白血症,感染时的炎性指标如白细胞总数、降钙素原、C反应蛋白均明显高于正常.结论 导管相关血流感染的患者,要积极改善血糖控制水平,纠正贫血和营养不良,同时给予针对性抗生素治疗,可以有效降低感染的发生率及改善疾病预后,提高患者生存率.

Background: Some studied reported the association between CCR5 rs333, rs1799987 and diabetic nephropathy (DN) risk. However, the results were controversial. Therefore, we performed this meta-analysis. Method: We searched PubMed and Embase databases. The strength of association was assessed by computing odds ratio (OR) with its corresponding 95% confidence interval (CI). Results: Nine studies with including 3475 cases and 3492 controls were included. The result showed that rs1799987 polymorphism significantly predicted DN risk (OR=1.38, 95% CI, 1.17-1.63). In the stratified analysis by ethnicity, the significant association was observed in Asians and Caucasians. In the subgroup analysis by type of diabetes, both T1D and T2D patients with rs1799987 polymorphism had increased DN risk. In addition, rs1799987 polymorphism significantly associated with EDN risk, while this polymorphism was not associated with AND risk. As for rs333, no significant association between this polymorphism and DN risk was found (OR=1.36, 95% CI, 0.79-2.33), even in the subgroup analyses. Conclusion: In conclusion, this meta-analysis suggests that individuals with CCR5 rs333 polymorphism may have an increased DN risk.

Non-alcoholic fatty liver disease (NAFLD) is a common liver disease and it represents the hepatic manifestation of metabolic syndrome, which includes type 2 diabetes mellitus (T2DM), dyslipidemia, central obesity and hypertension. Glucagon-like peptide-1 (GLP-1) analogues and dipeptidyl peptidase-4 (DPP-4) inhibitors were widely used to treat T2DM. These agents improve glycemic control, promote weight loss and improve lipid metabolism. Recent studies have demonstrated that the GLP-1 receptor (GLP-1R) is present and functional in human and rat hepatocytes. In this review, we present data from animal researches and human clinical studies that showed GLP-1 analogues and DPP-4 inhibitors can decrease hepatic triglyceride (TG) content and improve hepatic steatosis, although some effects could be a result of improvements in metabolic parameters. Multiple hepatocyte signal transduction pathways and mRNA from key enzymes in fatty acid metabolism appear to be activated by GLP-1 and its analogues. Thus, the data support the need for more rigorous prospective clinical trials to further investigate the potential of incretin therapies to treat patients with NAFLD.

The signal transducer and activator of transcription 4 (STAT4) rs7574865 polymorphism has been indicated to be correlated with type 1 diabetes (T1D) susceptibility, but study results are still debatable. Thus, a meta-analysis was conducted. The electronic databases PubMed, Embase, CNKI, and Web of Science (ISI) were searched to find eligible studies. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. A significant association was found between STAT4 rs7574865 polymorphism and T1D risk (OR=1.30; 95% CI, 1.13-1.48; P<0.01; I(2) =73%). Significant associations were also found in Asians (OR=1.33; 95% CI, 1.04-1.71; P=0.02; I(2) =60%) and Caucasians (OR=1.26; 95% CI, 1.08-1.47; P<0.01; I(2) =74%), respectively. This association was also positive in the pediatric patients (OR=1.41; 95% CI, 1.19-1.68; P<0.01; I(2) =46%). Moreover, we found that STAT4 rs7574865 polymorphism was associated with early-onset T1D risk (OR=1.43; 95% CI, 1.16-1.77; P<0.01; I(2) =0%). This meta-analysis suggested that the STAT4 rs7574865 polymorphism may be associated with T1D development.

口腔颌面部间隙感染为临床常见的面部感染疾病,若治疗不及时,加之糖尿病患者本身血糖控制差,感染细菌很容易入血,引起局部脓肿,甚至败血症,严重时可导致患者死亡.同时少数患者可以因感染导致急性视神经炎,影响患者视力.现报道此患者1例的诊断及治疗经过,希望加强对本病的认识,有利于指导临床治疗.

目的：探讨维持性血液透析患者静脉压高报警的原因及应急预防措施。方法：选取维持性血液透析患者60例，观察4680例次的血液透析，并研究263例次静脉压高报警的原因，及时给予干预。结果：本组263例次静脉压高报警原因：患者因素117例次、设备材料原因91例次、体内肝素化不足22例次、穿刺因素18例次、血流速度太慢15例次。结论：在维持性血液透析过程中，护理人员应加强巡视，及时发现并分析静脉压高报警原因，给予相应的处理和预防措施，从而确保血液透析的顺利进行。

目的 了解2型糖尿病(T2DM)患者医院感染的临床特点、病原菌分布及其对抗菌药物的耐药性.方法 对内分泌科2009年1月-2011年12月住院52例T2DM患者医院感染临床资料进行回顾性分析.结果 52例医院感染患者感染部位主要为泌尿系(25例)、呼吸道(18例)、肝脓肿(4例)、皮肤软组织(3例)及未发现明确感染部位(2例);检出病原菌以革兰阴性菌多见,其中大肠埃希菌26株、肺炎克雷伯菌16株、弗氏柠檬酸杆菌1株、葡萄球菌属7株、其他革兰阳性球菌2株;药敏试验中对革兰阴性杆菌敏感性较高的抗菌药物是亚胺培南及美罗培南,敏感率均为100.00％,其次是头孢哌酮/舒巴坦、哌拉西林/他唑巴坦及阿米卡星,敏感率分别为95.8％、90.5％和88.0％,对革兰阳性球菌敏感抗菌药物多为利奈唑胺、万古霉素、呋喃妥因,敏感率分别为100.0％、85.7％和85.7％.结论 T2DM合并败血症病原菌仍以革兰阴性杆菌多见,主要为大肠埃希菌及肺炎克雷伯菌;临床上早期诊断,积极抗感染治疗,同时应用胰岛素控制血糖,利于改善患者预后,临床宜根据药敏结果选择抗菌药物并合理使用,加强病原菌检测及耐药性监测.

Objective To observe the effect of levocarnitine combined with hemodialysis in the treatment of patients with uremic peripheral neuropathy.Methods Eighty-four patients with uremic peripheral neuropathy were randomly assigned to hemodialysis group(HD,n=30),hemodiafiltration group(HDF,n=27),or levocarnitine combined with hemodialysis group(LCN + HD,n=27).Patients in HD group received regular hemodialysis thrice a week.Patients in HDF group received regular hemodialysis twice a week and hemodiafiltration once a week.Patients in L-CN+HD group were given levocarnitine 2.0g dripped and intravenously thrice a week.Clinical symptoms and the sensory conduction velocity(SCV)of median nerve,tibial nerve and lateral popliteal nerve were observed in the three groups at baseline and after the treatment for 8 weeks.Results In HDF and L-CN+HD groups after the treatment for 8 weeks,peripheral neuropathy symptoms of Pain in the extremities、Sensory disturbances、 Numbness、Restless Legs Syndrom improved,as compared with HD group(χ 2 =13.87,17.52,25.37,9.20;P0.05),and SCV of L-CN+HD and HDF groups after the treatment became faster than that before treatment(t=L-CN+HD/ HDF=10.1/12.3,12.7/13.4,16.8/18.1;P0.05),with wider range of SCV change in treatment group than in HD group(F=25.63,32.83,22.5;P0.01).While the changes of SCV before and after the treatment for 8 weeks were statistically indifferent between HDF group and L-CN+HD group(F=0.613,P0.05).Conclusions Both levocarnitine combined with hemodialysis and hemodiafiltration are effective for the treatment of patients with uremic peripheral neuropathy.

Objective To investigate the changes of thyroid function in patients with end stage renal disease (ESRD) with or without dialysis. Methods Serum free-T3 (FT3), free-T4 (FT4) and thyrotropin (uTSH) concentrations were measured by electrochemiluminescence. These levels were compared in ESRD patients not on dialysis (n=42), those on hemodialysis (n=36), those on hemodialysis before and after hemodialysis sessions (n=12), and normal control subjects (n=30). Results (a) Compared with normal controls, serum levels of FT3 and FT4 were significantly lower (P< 0.05), and uTSH content was significantly higher (P < 0.01) in patients with ESRD. However, the differences of serum FT3 and FT4 levels were insignificant between ESRD patients on dialysis group and not on dialysis group (P > 0.05). (b) Serum FT3 and FT4 changed insignificantly in hemodialysis patients before and after hemodialysis sessions (P> 0.05). (c) The prevalence of hypothyroidism was higher in ESRD patients than in normal controls (P< 0.01), but the prevalence of hyperthyroidism was similar in ESRD patients and normal controls (P > 0.05). Conclusion Thyroid dysfunction with hypothyroidism is frequently found in ESRD patients. Dialysis can not change this abnormality.

Objective:To observe the effect of resistin on activity of glucoskinase(GK) and phosphoenolpyruvate carboxykinase(PEPCK) in cultured rat liver cells.Methods:Rat liver cells were incubated with resistin of different doses(ranging from 10nM/L to 100nM/L).Controled liver cells were invubated without resistin.Glucose-6-phosphate dehydrogenase couple chromatometry and lactate dehydrogenase couple chromatometry were used to determine activity of GK and PEPCK.Results:Compared with the control group,treated with resistin of 10nM/L and 50nM/L for 24h had no significant effect on activity of GK,but activity of PKPCK increased significantly(P0.05).At the dose of 100nM/L,resistin inhabited activity of GK markedly(P0.01),while activity of PKPCK increased more significantly(P0.01).Conclusion:The increase of Resistin leads to the decrease of activity of GK and increase of activity of PEPCK in rat liver cells,hence inhabite glycolysis and promote glyconeogenesis and increase blood glucose as well.The activity of two enzymes shows dose dependent relation with resistin.