Therapeutic effects of melatonin on heatstroke-induced multiple organ dysfunction syndrome in rats

Abstract: Melatonin reportedly exerts beneficial effects to attenuate multiple organ dysfunction syndrome (MODS) in septic shock. Heatstroke resembles septic shock in many aspects. Thus, this study was performed on the anesthetized rats by using heat exposure to induce heatstroke‐associated MODS. We evaluated the effect of melatonin, a versatile molecule synthesized in the pineal gland and in many organs, in heatstroke rats and showed that melatonin (0.2–5.0 mg/kg of body weight, i.v., immediately after the start of heat stress) significantly (i) attenuated hyperthermia, hypotension and hypothalamic ischemia and hypoxia, (ii) reduced plasma index of the toxic oxidizing radicals like nitric oxide metabolites and hydroxyl radicals, (iii) diminished plasma index of hepatic and renal dysfunction like creatinine, blood urea nitrogen, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and lactate dehydrogenase, (iv) attenuated plasma systemic inflammation response molecules like soluble intercellular and lesion molecule‐1, E‐selectin, tumor necrosis factor‐alpha, interleukin (IL)‐1β, and IL‐6, (v) promoted plasma levels of an anti‐inflammatory cytokine IL‐10, (vi) reduced an index of infiltration of polymorphonuclear neutrophils in the lung like myeloperoxidase activity, and (vii) promoted the survival time to fourfold compared with the heatstroke alone group. Thus, melatonin could be a novel agent for the treatment of heatstroke animals or patients in the early stage.     

Gastric metaplasia of the duodenum: in vivo diagnosis by endomicroscopy and its relationship with functional dyspepsia

Background and Aim: Gastric metaplasia (GM) of the duodenum is difficult to assess because of its patchy distribution, and the role of GM in functional dyspepsia (FD) is not clear. The aims of this study were to determine if endomicroscopy could identify GM of the duodenum and whether GM has associations with FD. Methods: A series of 51 patients with FD and 25 asymptomatic controls were enrolled. Confocal laser endomicroscopy was performed to evaluate villi changes in vivo. Targeted biopsy specimens were then compared with histopathological results. Results: The accuracy of the endomicroscopy diagnosis of GM during endoscopy was 92.8%, and the sensitivity, specificity, and positive and negative predictive values were 86.2%, 97.4%, 89.3%, and 96.6%, respectively. The mean κ‐value for interobserver agreement was 0.89. GM in the duodenal bulb was more frequent in patients with FD than in the controls (33.3% vs 12%, P < 0.05), especially in patients with epigastric pain syndrome (47.6% vs 12%, P < 0.01). Conclusions: Endomicroscopy is useful for identifying GM, and GM might be related to FD. These findings could have potential applicability for duodenal screening, and suggest a possible targeting therapy in FD.     

Dexamethasone attenuates lipopolysaccharide-induced liver injury by downregulating glucocorticoid-induced tumor necrosis factor receptor ligand in Kupffer cells

Aim: Glucocorticoid‐induced tumor necrosis factor receptor ligand (GITRL) plays pro‐inflammatory roles in immune response. Thus, our aim was to assess if dexamethasone attenuates lipopolysaccharide (LPS)‐induced liver injury by affecting GITRL in Kupffer cells (KC). Methods: A BALB/c mouse model of liver injury was established by i.p. injecting with LPS (10 mg/kg) co‐treated with or without dexamethasone (3 mg/kg). Blood and liver samples were obtained for analysis of liver morphology, GITRL expression, hepatocellular function and cytokine levels at 24 h after injection. KC were isolated and challenged by LPS (1 µg/mL), with or without dexamethasone (10 µM) co‐treatment, or with GITRL siRNA pre‐transfection. The GITRL expression and cytokine levels were assayed at 24 h after challenge. Results: Dexamethasone treatment significantly improved the survival rate of endotoxemic mice (P < 0.05), whereas serum alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor (TNF)‐α, interleukin (IL)‐6 and γ‐interferon levels were significantly decreased (P < 0.05, respectively). Concurrently, LPS‐induced hepatic tissue injury was attenuated as indicated by morphological analysis; and expression of GITRL in liver tissue and KC was downregulated (P < 0.05). Consistent with these in vivo experiments, inhibited expression of GITRL, TNF‐α and IL‐6 caused by dexamethasone treatment were also observed in LPS‐stimulated KC. The GITRL, TNF‐α and IL‐6 expression was also significantly inhibited by GITRL gene silencing. Conclusion: The TNF‐α and IL‐6 expression of LPS‐stimulated KC was inhibited by GITRL gene silencing. Dexamethasone attenuates LPS‐induced liver injury, at least proportionately, by downregulating GITRL in KC.     

双相障碍临床研究现状与趋势

与抑郁障碍相比,双相障碍的临床表现和病程更复杂,治疗更困难,预后更差,自杀风险更大。据报道,双相谱系障碍的患病率为6%,但是在世界范围内尤其是在中国,对这类疾病的识别率和治疗率很低。临床医生需要更熟悉＂软双相＂的症状,更准确地鉴别双相抑郁与单相抑郁,更准确地区分出共病双相障碍的其他精神障碍,并为预防双相障碍的复发提供更有效的维持治疗。对双相谱系障碍的临床研究需要有效地整合心理治疗和生物治疗。     

胚胎干细胞核心转录因子靶基因集蛋白互作网络特征分析

背景：外源性核心转录因子导入终末分化细胞能产生具有与胚胎干细胞特性相似的诱导多潜能干细胞,其复杂机制目前尚未完全阐明。 目的：分析核心转录因子靶基因集蛋白互作网络特征,获得其影响“干性”特征的调控机制。 方法：去除BioGRID数据库中的冗余数据,获得非冗余蛋白互作数据库。perl程序搜索靶基因集组成的蛋白互作对,广度优先算法搜索非冗余蛋白互作数据库,获得靶基因集组成的最大连续蛋白互作网络,同时进行1 000次随机抽样网络分析。通过Cytoscape软件对网络进行可视化分析。复杂无标度网络Barabasi-Albert模型分析网络特征。 结果与结论：核心转录因子靶基因集形成更多的蛋白互作对,最大连续蛋白网络与随机蛋白网络相比具有明显的统计学差异,且核心转录因子靶基因集形成更大的互作网络。网络具有复杂网络无标度特性。该研究通过蛋白互作网络分析证明：靶基因集通过紧密相互作用,形成网络模块方式协调调控胚胎干细胞分子特性。     

计算机辅助数学模型分析Twin-block功能矫治后的组织相关性☆

背景：功能矫治器的观察对象都是处于生长期的青少年,在研究功能矫治是否有效的问题时,必须要考虑儿童本身的生长发育条件。 目的：排除自然生长因素对实验结果的影响,采用计算机辅助数学分析Twin-block矫治器治疗后Ⅱ类错牙合患者颅颌面软硬组织的相关性。 方法：选择Hagg手腕骨片为FG-G期的安氏Ⅱ类1分类下颌后缩患者31例,其中接受Twin-block功能矫治的Ⅱ类错牙合患者17例,放弃正畸治疗的Ⅱ类错牙合患者14例,2组患者年龄、性别相匹配。分别在治疗前后和自然生长前后拍摄头颅侧位片,观察Twin-block功能矫治前后和自然生长前后侧位片软硬组织头影测量值的变化规律,建立两组数学对比模型。 结果与结论：通过数学对比模型发现,在Twin-block矫治后软组织测量项目Ls-EP、Pn-HP、NB-Pg’-Ls与硬组织测量项目ANB之间存在明显的曲线关系,方程为：NB-Pg’ -Ls=-0.119 1(ANB)2 +3.002 9(ANB)+ 6.148 5,Pn-HP=0.021 4(ANB)2 -1.026 7(ANB)+ 0.347 4,Ls-EP =0.132 4(ANB)2 -0.536 4(ANB)+1.553 7。在自然生长前后,软硬组织的改变差异无显著性意义。提示Twin-block矫治后ANB的角度是改善Ⅱ类错牙合患者软组织侧貌的决定性因素。     

退变性腰椎疾患小关节囊中P物质的表达及其意义

[摘要] 目的 探讨退变性腰椎疾患中小关节囊病理变化及其疼痛机理。 方法 采用术前诊断性封闭方法筛选出18例退变性慢性腰痛患者,行小关节囊切除,切除的小关节囊标本作为实验组,选取18例骨折前无腰痛的腰椎骨折患者的小关节囊标本为对照组,进行P物质（Substance P,SP）免疫组化染色,观察SP免疫组化染色阳性神经纤维的分布情况。结果 实验组中13例可见SP阳性神经纤维,5例未见阳性反应。SP神经纤维在小关节囊内的定位与分布基本一致,关节囊上的SP神经纤维大部分沿血管走行,血管周围阳性神经纤维密度较大,也有一些SP 神经不与血管伴行,独立走行于关节囊基质中,另外在小关节软骨下骨区亦有少量独立走行的SP纤维。对照组腰椎小关节囊中3例可见少量SP阳性神经纤维,15例为阴性。结论 腰椎小关节囊病理改变与退变性腰痛有明显关系,小关节囊中SP阳性神经纤维可能参与了退变性腰痛疼痛的发生。小关节囊病理改变在小关节源性腰痛发生中起重要作用。