Insomnia symptoms are associated with an increased risk of type 2 diabetes mellitus among adults aged 50 and older

Purpose

To evaluate the association of the different degrees of insomnia symptoms with subsequent incidence of type 2 diabetes mellitus (T2DM).

Methods

The data were extracted from Health and Retirement Study 2006–2014 waves. The association of insomnia symptoms with T2DM incidence was evaluated by the competing risk model with cumulative incidence function (death was considered a competing event) and Cox proportional hazard model with the Kaplan–Meier method. Population attributable fraction (PAF) was calculated. All analyses related to our study were conducted between November 2020 and January 2021.

Results

A total of 14,112 patients were included in this study, with an average follow-up of 6.4 years, and the incidence density was 17.9 per 1000 person-years. Insomnia symptoms were positively associated with T2DM incidence compared with those with no insomnia symptoms, regardless of competing risk model (≥?1 symptoms: sub-distribution hazard ratio (SHR) 1.13; 95% confidence interval (CI) 1.02–1.26; P-trend?=?0.012) and Cox proportional hazard model (≥?1 symptoms: hazard ratio (HR) 1.13; 95% CI 1.02–1.26; P-trend?=?0.013). The cumulative incidence function (Gray’s test, p?<?0.001) and Kaplan–Meier estimate (log-rank test, p?<?0.001) also presented this positive relationship. This positive association was more apparent in women and participants with ages from 50 to 65 years. The PAF was 4.1% with 95% CI (0.7–7.9%).

Conclusions

Insomnia symptoms may be an important risk factor for the development of T2DM, which is unbiased by the death competing risk. These findings suggest that management of sleep problems may be an important part of strategies to prevent T2DM.

     

Cholangiocyte endothelin 1 and transforming growth factor beta1 production in rat experimental hepatopulmonary syndrome

BACKGROUND & AIMS: Hepatic production and release of endothelin 1 plays a central role in experimental hepatopulmonary syndrome after common bile duct ligation by stimulating pulmonary endothelial nitric oxide production. In thioacetamide-induced nonbiliary cirrhosis, hepatic endothelin 1 production and release do not occur, and hepatopulmonary syndrome does not develop. However, the source and regulation of hepatic endothelin 1 after common bile duct ligation are not fully characterized. We evaluated the sources of hepatic endothelin 1 production after common bile duct ligation in relation to thioacetamide cirrhosis and assessed whether transforming growth factor beta1 regulates endothelin 1 production. METHODS: Hepatopulmonary syndrome and hepatic and plasma endothelin 1 levels were evaluated after common bile duct ligation or thioacetamide administration. Cellular sources of endothelin 1 were assessed by immunohistochemistry and laser capture microdissection of cholangiocytes. Transforming growth factor beta1 expression and signaling were assessed by using immunohistochemistry and Western blotting and by evaluating normal rat cholangiocytes. RESULTS: Hepatic and plasma endothelin 1 levels increased and hepatopulmonary syndrome developed only after common bile duct ligation. Hepatic endothelin 1 and transforming growth factor beta1 levels increased over a similar time frame, and cholangiocytes were a major source of each peptide. Transforming growth factor beta1 signaling in cholangiocytes in vivo was evident by increased phosphorylation and nuclear localization of Smad2, and hepatic endothelin 1 levels correlated directly with liver transforming growth factor beta1 and phosphorylated Smad2 levels. Transforming growth factor beta1 also stimulated endothelin 1 promoter activity, expression, and production in normal rat cholangiocytes. CONCLUSIONS: Cholangiocytes are a major source of hepatic endothelin 1 production during the development of hepatopulmonary syndrome after common bile duct ligation, but not in thioacetamide-induced cirrhosis. Transforming growth factor beta1 stimulates cholangiocyte endothelin 1 expression and production. Cholangiocyte-derived endothelin 1 may be an important endocrine mediator of experimental hepatopulmonary syndrome.     

Evaluation of a rapid test for the detection of antibodies to human immunodeficiency virus type 1 and 2 in the setting of multiple transmitted viral subtypes

Rapid HIV testing is an appealing strategy in the approach to HIV diagnosis in developing countries. Concern has been raised about the use of these tests in the setting of multiple transmitted HIV subtypes. We sought to compare the OraQuick(TM) HIV-1/2 Test, a qualitative immunochromatographic test for the detection of antibodies to HIV-1 and HIV-2 using stored sera, with a conventional enzyme immunoassay (EIA)/Western blot (WB) algorithm. The study design used was a blinded retrospective study. Samples were collected on patients attending sexually transmitted disease clinics and tuberculosis clinics in Kinshasa, the Democratic Republic of Congo and included 72 known HIV seropositive and 131 known HIV seronegative subjects. All 72 known HIV seropositive samples were positive by OraQuick and all 131 known HIV seronegative samples were negative by OraQuick resulting in 100% sensitivity and specificity. We conclude that the OraQuick rapid HIV-1/2 test performs well in the setting of diverse HIV viral subtypes.     

Tegaserod does not alter fasting or meal-induced biliary tract motility

OBJECTIVE: Tegaserod is a 5-HT(4) receptor partial agonist that increases peristaltic activity of the intestinal tract. It is approved for the treatment of patients with irritable bowel syndrome with constipation (IBS-C). IBS is a chronic gastrointestinal disorder of function that is reported to be associated with an increased incidence of abdominal surgery including cholecystectomy. The effect of tegaserod on nongut digestive organs, such as the gallbladder and biliary tract, has not been previously investigated. Therefore, this study aimed to evaluate the effects of tegaserod on gallbladder contractility and on functional status of the sphincter of Oddi during both the interdigestive and the digestive periods in healthy female subjects and in female patients with IBS-C. METHODS: During a 6-wk, double-blind, placebo-controlled crossover study, gallbladder contractility and concomitant change in luminal diameter of the common hepatic duct (CHD) and the common bile duct (CBD, both proximal and distal) in response to a standard liquid meal were quantified using real-time ultrasonography. Changes in luminal diameter of the CHD and the CBD were used as a surrogate marker for sphincter of Oddi function. Ultrasound measurements were conducted every 15 min from 45 min before, to 60 min after the test meal to observe the impact of tegaserod on gallbladder volume and any concomitant change in the diameters of the CHD and the CBD that developed in response to gallbladder contraction. The ultrasound measurements of gallbladder contractility, along with the CHD and the CBD diameters, were repeated after each of the two 2-wk periods of treatment with tegaserod or placebo. The recommended dose of tegaserod (6 mg b.i.d.) for IBS-C patients was used in healthy female subjects (n = 13) and female patients with IBS-C (n = 20). Twice this dose (12 mg b.i.d.) was also evaluated in an additional 20 female patients with IBS-C. Statistical evaluations were conducted using a two-sided analysis of variance (ANOVA). RESULTS: Gallbladder contractility variables including ejection fraction, ejection rate and ejection period, fasting and residual volume, and maximal emptying, were similar after 2 wk of treatment with tegaserod 6 mg b.i.d. and placebo in healthy female subjects and female patients with IBS-C. There were no significant changes in the luminal diameters of the CHD or the CBD after tegaserod compared to placebo in any cohort. Additionally, no significant dilation (> or =7 mm in diameter) of the CHD or CBD was observed during maximal gallbladder emptying. Similar results were also observed when tegaserod was given at 12 mg b.i.d. in patients with IBS-C. Tegaserod treatment had no significant effect on plasma CCK concentration in response to the test meal. No significant abdominal pain or unexpected adverse events were reported during the study. CONCLUSIONS: This study showed no significant pharmacodynamic effect of tegaserod on gallbladder contractility or on CBD and CHD diameters as a surrogate marker of sphincter of Oddi function during both the interdigestive (fasting) and the digestive (postprandial) periods in healthy female subjects and female patients with IBS-C.     

72例鼻咽结核的临床分析

目的 探讨鼻咽结核的诊断与治疗。方法 对72例经活检病理证实的鼻咽结核进行回顾性分析。结果 72例患者中男性31例，女性41例，男女比例为1：1．32，平均年龄为30．7岁；鼻咽结核以局部症状为特征，颈淋巴结肿大发生率为79．2％（57／72）；鼻咽结核在临床上误诊率较高；抗结核治疗9～12个月治愈，随访1～5年，未见复发。结论 近年来鼻咽结核有增加的趋势，尤以原发性病例居多。鼻咽镜活检可确诊，规则抗结核治疗可治愈。     

Intestinal signaling to GABAergic neurons regulates a rhythmic behavior in Caenorhabditis elegans

The Caenorhabditis elegans defecation motor program (DMP) is a highly coordinated rhythmic behavior that requires two GABAergic neurons that synapse onto the enteric muscles. One class of DMP mutants, called anterior body wall muscle contraction and expulsion defective (aex) mutants, exhibits similar defects to those caused by the loss of these two neurons. Here, we demonstrate that aex-2 encodes a G-protein-coupled receptor (GPCR) and aex-4 encodes an exocytic SNAP25 homologue. We found that aex-2 functions in the nervous system and activates a G(s)alpha signaling pathway to regulate defecation. aex-4, on the other hand, functions in the intestinal epithelial cells. Furthermore, we show that aex-5, which encodes a pro-protein convertase, functions in the intestine to regulate the DMP and that its secretion from the intestine is impaired in aex-4 mutants. Activation of the G(s)alpha GPCR pathway in GABAergic neurons can suppress the defecation defect of the intestinal mutants aex-4 and aex-5. Lastly, we demonstrate that activation of GABAergic neurons using the light-gated cation channel channelrhodopsin-2 is sufficient to suppress the behavioral defects of aex-2, aex-4, and aex-5. These results genetically place intestinal genes aex-4 and aex-5 upstream of GABAergic GPCR signaling. We propose a model whereby the intestinal genes aex-4 and aex-5 control the DMP by regulating the secretion of a signal, which activates the neuronal receptor aex-2.     

Modulation of platelet and leucocyte function by a Chinese herbal formulation as compared with conventional antiplatelet agents

Platelet and leucocyte activity are important in the acute development of thrombosis and in the pathogenesis of ischaemic vascular disease. Dan Shen Di Wan (DS, Cardiotonic Pill or Dantonic(R) Pill) is one of the most commonly used Chinese herbal formulations for treating patients with atherosclerotic disease in China and several Asian countries. We studied the effect of DS on platelet and leucocyte function and compared the effects with conventional antiplatelet agents, cangrelor (ADP P2Y(12) receptor antagonist) and aspirin (acetyl salicylic acid, ASA). Measurements were made by platelet aggregation (%) and activation (CD62P %), platelet-monocyte conjugate formation (P/M, CD42a median fluorescence, mf), platelet-neutrophil conjugate formation (P/N, mf), and leucocyte activation (CD11b median fluorescence on monocytes and neutrophils, mf) in response to 3.3 micromol/L adenosine diphosphate (ADP), 1.0 micromol/L platelet activating factor (PAF), 5.0 micromol/L adrenaline and 0.5 microg/mL collagen. We also evaluated the effect of its main component, water soluble extract of salvia miltiorrhiza (SME) on intracellular calcium mobilization in platelets triggered by 10 micromol/L ADP, 10 micromol/L PAF, 2 microg/mL collagen and 15 micromol/L thrombin receptor activating peptide (TRAP). Overall DS showed inhibition of platelet aggregation, platelet activation, platelet-leucocyte conjugate formation and leucocyte activation in response to all the agonists apart from adrenaline (all p < 0.01). DS showed inhibition of platelet aggregation and leucocyte activation equivalent to cangrelor 100 nmol/L and ASA 100 micromol/L. SME dose-dependently inhibited intracellular calcium mobilization in platelets following stimulation with all the platelet agonists with maximum effective at 0.36 mg/mL (all p < 0.01). When used at 0.18 mg/mL its inhibitory effect was equivalent to cangrelor and ASA. We conclude that DS is a potential inhibitor of both platelet and leucocyte activation.     

中性粒细胞与淋巴细胞比值、血小板与淋巴细胞比值在重症肺炎支原体肺炎中的诊断价值北大核心CSCD

目的研究中性粒细胞与淋巴细胞比值(NLR)及血小板与淋巴细胞比值(PLR)在重症肺炎支原体肺炎(MPP)中的诊断价值。方法回顾性分析2015年1月至2017年12月苏州大学附属儿童医院住院的616例MPP患儿(MPP组)的临床资料和实验室数据,选取同期100例健康体检儿童为健康对照组。采用t检验或秩和检验比较MPP组与健康对照组、重症MPP组与普通MPP组间的NLR及PLR的差异。筛选出影响重症MPP的危险因素,描绘受试者工作特征曲线(ROC)并寻找最佳截断点。结果1.MPP组患儿白细胞计数(WBC)、中性粒细胞数(N)、血小板计数(PLT)、NLR、PLR、免疫球蛋白(Ig)M的中位数及CD3^(-)CD_(19)^(+)、CD_(19)^(+)CD_(23)^(+)百分比的中位数均高于健康对照组[8.36×10^(9)/L比7.49×10^(9)/L、4.41×10^(9)/L比3.11×10^(9)/L、340.92×10^(9)/L比234.00×10^(9)/L、1.70比0.91、112.99比70.34、1.33 g/L比1.29 g/L、20.95%比17.10%、11.25%比9.70%];淋巴细胞数(L)、IgA的中位数及CD3^(+)、CD3^(+)CD8^(+)、CD3^(-)CD_((16+56))^(+)百分比的中位数均低于健康对照组[2.64×10^(9)/L比3.37×10^(9)/L、0.86 g/L比1.30 g/L、64.55%比68.00%、23.65%比24.90%、10.50%比12.20%],差异均有统计学意义(Z=-3.074、-2.413、-2.972、-1.357、-1.863、-2.251、-4.282、-3.420、-2.221、-4.181、-2.784、-2.024、-2.791,均P<0.05)。2.重症MPP组患儿N、NLR、PLR、IgA、IgG、IgM的中位数及CD3^(+)、CD3^(+)CD8^(+)百分比均高于普通MPP组[5.18×10^(9)/L比3.52×10^(9)/L、2.39比1.03、149.32比94.23、1.29 g/L比0.71 g/L、9.63 g/L比8.19 g/L、1.40 g/L比1.29 g/L、(65.53±9.75)%比(62.81±9.89)%、(25.35±6.65)%比(23.38±6.91)%];L的中位数、CD3^(-)CD_(19)^(+)、CD_(19)^(+)CD_(23)^(+)百分比的中位数均低于普通MPP组(2.02×10^(9)/L比3.25×10^(9)/L、17.40%比21.50%、9.00%比11.70%),差异均有统计学意义(Z/t=-7.807、-11.313、-10.452、-8.819、-6.162、-3.047、-3.128、-3.270、-9.402、-5.191、-5.214,均P<0.05)。3.通过单因素和多因素的Logistic回归分析发现,CD3^(-)CD_(19)^(+)是患儿发生重症MPP的保护因素;N、NLR、PLR是患重症MPP的危险因素(均P<0.05),且相对危险度由高到低依次为NLR>PLR>N。4.NLR、PLR诊断重症MPP的ROC曲线下面积(AUC)分别为:NLR(AUC=0.789,95%CI:0.754~0.823,P<0.001);PLR(AUC=0.767,95%CI:0.730~0.804,P<0.001)。当NLR的截断值为1.09时,敏感性为98.9%,特异性为70.6%;当PLR的截断值为97.47时,敏感性为88.5%,特异性为69.4%。结论NLR、PLR可作为发生重症MPP的独立影响因素,对诊断重症MPP有一定价值。     

左乙拉西坦的国产仿制药替换治疗儿童癫痫的疗效及安全性研究北大核心CSCD

目的评价左乙拉西坦的国产仿制药替换原研药进口左乙拉西坦治疗儿童癫痫的疗效及安全性。方法回顾性分析2019年5月至2020年12月在广东省人民医院住院或门诊接受左乙拉西坦的国产仿制药替换治疗的154例癫痫患儿的临床资料,分析比较左乙拉西坦的国产仿制药替换原研药治疗的效果及安全性。结果154例患儿基线期癫痫控制率为77.3%(119/154),替换治疗6个月后癫痫控制率达83.8%(129/154),差异有统计学意义(P<0.05)。基线期与替换治疗6个月后癫痫发作频率比较差异无统计学意义(P>0.05)。替换治疗后无效患儿出现难治性癫痫比例高于有效患儿(P<0.05)。替换治疗前,仅1例患儿(0.6%)出现嗜睡;替换治疗后,3例患儿(1.9%)观察到轻度药物不良反应,包括头晕、嗜睡、易激惹、脾气暴躁,与替换治疗前比较差异无统计学意义(P>0.05)。结论左乙拉西坦的国产仿制药替换原研药进口左乙拉西坦治疗儿童癫痫是安全有效的,值得推广,但是需要更多的前瞻性随机对照试验来证实。