不同营养状况与慢性阻塞性肺病患者预后的相关性分析

<正>慢性阻塞性肺病(chronic obstructive pulmonary diseases,COPD)在临床呼吸科发病率与病死率排名首位,使患者的生命受到严重威胁[1]。COPD患者由于消化、呼吸功衰退,营养吸收功能减弱,同时气道阻力升高,减弱了肺部顺应性,所以伴发能量不足型营养障碍的机率较高[2-3]。出现营养不良的患者往往疾病加重,影响预后,而临床COPD患者疾病严重程度与预后又同肺功能变化密切相关[4]。本文分析了不同营养状况与COPD患者预后的相关性。     

Helicobacter pylori induces epithelial-mesenchymal transition in gastric carcinogenesis via the AKT/GSK3β signaling pathway

Helicobacter pylori (H. pylori) is a main risk factor for gastric cancer (GC). Epithelial-mesenchymal transition (EMT) is involved in the development and progression of H. pylori-associated GC. However, the exact molecular mechanism of this process remains unclear. The AKT/GSK3β signaling pathway has been demonstrated to promote EMT in several types of cancer. The present study investigated whether H. pylori infection induced EMT, and promoted the development and metastasis of cancer in the normal gastric mucosa, and whether this process was dependent on AKT activation. The expression levels of the EMT-associated proteins, including E-cadherin and N-cadherin, were determined in 165 gastric mucosal samples of different disease stages by immunohistochemical analysis. The expression levels of E-cadherin, N-cadherin, AKT, phosphorylated (p-)AKT (Ser473), GSK3β and p-GSK3β (Ser9) were further determined in H. pylori-infected Mongolian gerbil gastric tissues and cells co-cultured with H. pylori by immunohistochemical analysis and western blotting. The results indicated that the expression levels of the epithelial marker E-cadherin were decreased, whereas the expression levels of the mesenchymal marker N-cadherin were increased during gastric carcinogenesis. Their expression levels were associated with H. pylori infection. Furthermore, H. pylori infection resulted in downregulation of E-cadherin expression and upregulation of N-cadherin expression in Mongolian gerbils and GES-1 cells. In addition, an investigation of the associated mechanism of action revealed that p-AKT (Ser473) and p-GSK3β (Ser9) were activated in GES-1 cells following co-culture with H. pylori. Furthermore, following pretreatment of the cells with the AKT inhibitor VIII, the expression levels of E-cadherin, N-cadherin, p-AKT and p-GSK3β did not show significant differences between GES-1 cells that were co-cultured with or without H. pylori. The levels of p-AKT and p-GSK3β were increased in H. pylori-infected Mongolian gerbils. In conclusion, the present study demonstrated that H. pylori infection activated AKT and resulted in the phosphorylation and inactivation of GSK3β, which in turn promoted early stage EMT. These effects were AKT-dependent. This mechanism may serve as a prerequisite for GC development.     

热疗对肿瘤免疫微环境中免疫细胞及免疫相关细胞因子的影响

随着对肿瘤热疗和肿瘤免疫微环境(TIME)的深入研究,近年来热疗对TIME的作用越来越受到学者们的重视。本文就目前国内外研究进展,对热疗与TIME中几类主要免疫细胞和免疫相关细胞因子的影响及作用机制作一综述。全面而透彻的了解热疗对TIME的调控作用,有助于为肿瘤治疗提供新的思路和方法。     

Melatonin induces apoptosis of colorectal cancer cells through HDAC4 nuclear import mediated by CaMKII inactivation

Melatonin induces apoptosis in many different cancer cell lines, including colorectal cancer. However, the precise mechanisms involved remain largely unresolved. In this study, we provide evidence to reveal a new mechanism by which melatonin induces apoptosis of colorectal cancer LoVo cells. Melatonin at pharmacological concentrations significantly suppressed cell proliferation and induced apoptosis in a dose‐dependent manner. The observed apoptosis was accompanied by the melatonin‐induced dephosphorylation and nuclear import of histone deacetylase 4 (HDAC4). Pretreatment with a HDAC4‐specific siRNA effectively attenuated the melatonin‐induced apoptosis, indicating that nuclear localization of HDAC4 is required for melatonin‐induced apoptosis. Moreover, constitutively active Ca²⁺/calmodulin‐dependent protein kinase II alpha (CaMKIIα) abrogated the melatonin‐induced HDAC4 nuclear import and apoptosis of LoVo cells. Furthermore, melatonin decreased H3 acetylation on bcl‐2 promoter, leading to a reduction of bcl‐2 expression, whereas constitutively active CaMKIIα(T286D) or HDAC4‐specific siRNA abrogated the effect of melatonin. In conclusion, the present study provides evidence that melatonin‐induced apoptosis in colorectal cancer LoVo cells largely depends on the nuclear import of HDAC4 and subsequent H3 deacetylation via the inactivation of CaMKIIα.     

液体复苏在高呼吸末正压通气导致的肺泡微循环障碍中的作用

目的明确高呼气末正压（PEEP）条件下肺泡微循环的变化情况以及液体复苏在高PEEP情况下对肺泡微循环的影响。 方法选用北京当地的15条健康成年杂种狗进行实验，分别观察基线（PEEP 5 cmH₂O，1 cmH₂O=0.098 kPa）、高PEEP（平均动脉压下降≥20 mmHg，1 mmHg=0.133 kPa）及液体复苏后的呼吸、系统循环及肺泡微循环情况，肺泡微循环利用旁流暗视野成像（SDF）技术进行观察、留取视频结果，线下利用AVA3.2软件进行分析，不同条件下的实验数据之间的差异利用Wilcoxon秩和检验进行分析。 结果高PEEP可导致中心静脉压（CVP）升高（P=0.001）及心输出量（CO）下降（P=0.002），肺泡微循环表现为总微血管数量（TVDa，P=0.036）、灌注血管数量（PVDa，P=0.002）、灌注血管比例（PPVa，P=0.003）、血流状态（MFIa，P=0.002）显著下降，肺泡周围毛细血管密度下降不明显（TVDs，P=0.319）；液体复苏恢复整体循环后，微循环参数均无显著改善。 结论过高的PEEP水平可导致肺泡微循环的显著恶化，通过液体复苏不能改善由此产生的微循环障碍。     

临床医学专业“5+3”一体化本科全程导师制创新人才培养的实践与探索

以培养创新型人才为目标，大连医科大学制定实施了“5+3”创新人才培养改革方案，以导师制培养为载体，在医学本科教育全过程中，制定分阶段创新能力培养体系，涵盖课程、讲座、实验设计、论文等基本科研能力训练，强化本科生科研能力培养。通过对首届“5+3”学生阶段性培养成果的统计学分析发现，“5+3”学生发表中文期刊、SCI，主持国家级创新项目、省级创新项目的比例均显著高于普通5年制学生，差异具有统计学意义（P<0.05）。虽然实施过程中存在一些问题和不足，但以导师制为核心的科研基础训练对提高学生科研思维和创新能力效果显著，对培养医学创新型人才具有可实施性。     

Quantitative chemical exchange saturation transfer (qCEST) MRI – omega plot analysis of RF‐spillover‐corrected inverse CEST ratio asymmetry for simultaneous determination of labile proton ratio and exchange rate

Chemical exchange saturation transfer (CEST) MRI is sensitive to labile proton concentration and exchange rate, thus allowing measurement of dilute CEST agent and microenvironmental properties. However, CEST measurement depends not only on the CEST agent properties but also on the experimental conditions. Quantitative CEST (qCEST) analysis has been proposed to address the limitation of the commonly used simplistic CEST‐weighted calculation. Recent research has shown that the concomitant direct RF saturation (spillover) effect can be corrected using an inverse CEST ratio calculation. We postulated that a simplified qCEST analysis is feasible with omega plot analysis of the inverse CEST asymmetry calculation. Specifically, simulations showed that the numerically derived labile proton ratio and exchange rate were in good agreement with input values. In addition, the qCEST analysis was confirmed experimentally in a phantom with concurrent variation in CEST agent concentration and pH. Also, we demonstrated that the derived labile proton ratio increased linearly with creatine concentration (P < 0.01) while the pH‐dependent exchange rate followed a dominantly base‐catalyzed exchange relationship (P < 0.01). In summary, our study verified that a simplified qCEST analysis can simultaneously determine labile proton ratio and exchange rate in a relatively complex in vitro CEST system. Copyright © 2015 John Wiley & Sons, Ltd.