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.     

HIFα Regulates Developmental Myelination Independent of Autocrine Wnt Signaling

The developing CNS is exposed to physiological hypoxia, under which hypoxia-inducible factor α (HIFα) is stabilized and plays a crucial role in regulating neural development. The cellular and molecular mechanisms of HIFα in developmental myelination remain incompletely understood. A previous concept proposes that HIFα regulates CNS developmental myelination by activating the autocrine Wnt/β-catenin signaling in oligodendrocyte progenitor cells (OPCs). Here, by analyzing a battery of genetic mice of both sexes, we presented in vivo evidence supporting an alternative understanding of oligodendroglial HIFα-regulated developmental myelination. At the cellular level, we found that HIFα was required for developmental myelination by transiently controlling upstream OPC differentiation but not downstream oligodendrocyte maturation and that HIFα dysregulation in OPCs but not oligodendrocytes disturbed normal developmental myelination. We demonstrated that HIFα played a minor, if any, role in regulating canonical Wnt signaling in the oligodendroglial lineage or in the CNS. At the molecular level, blocking autocrine Wnt signaling did not affect HIFα-regulated OPC differentiation and myelination. We further identified HIFα–Sox9 regulatory axis as an underlying molecular mechanism in HIFα-regulated OPC differentiation. Our findings support a concept shift in our mechanistic understanding of HIFα-regulated CNS myelination from the previous Wnt-dependent view to a Wnt-independent one and unveil a previously unappreciated HIFα–Sox9 pathway in regulating OPC differentiation.SIGNIFICANCE STATEMENT Promoting disturbed developmental myelination is a promising option in treating diffuse white matter injury, previously called periventricular leukomalacia, a major form of brain injury affecting premature infants. In the developing CNS, hypoxia-inducible factor α (HIFα) is a key regulator that adapts neural cells to physiological and pathologic hypoxic cues. The role and mechanism of HIFα in oligodendroglial myelination, which is severely disturbed in preterm infants affected with diffuse white matter injury, is incompletely understood. Our findings presented here represent a concept shift in our mechanistic understanding of HIFα-regulated developmental myelination and suggest the potential of intervening with an oligodendroglial HIFα-mediated signaling pathway to mitigate disturbed myelination in premature white matter injury.     

关于医学教育专业人才培养方案修订的几点思考

随着“健康中国”战略的实施，需要建立与之相匹配的“新医科”人才培养体系，“基于医疗卫生系统的需求，以职业胜任力为导向”的教育教学改革势在必行。因此修订人才培养方案时要以胜任力为目标驱动重新梳理培养目标和毕业要求；采用“课程矩阵”设计法，反向设计、正向施工的原则优化课程体系；根据课程目标凝炼课程内容、精炼核心课程；充分利用网络开放课程资源，选修课分模块化设置；通过多种形式将创新创业教育贯穿人才培养全过程。     

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。     

中国县级及以上医疗机构青光眼诊疗服务 现状分析

目的：统计分析中国县级及以上医疗机构青光眼亚专科建设、诊疗设备配备和服务提供情况，为进 一步推动我国青光眼防治工作提供理论依据。方法：调查研究。2015年对全国提供眼科服务的县级 及以上医疗机构通过网上填报的方式进行普查，采用描述性统计方法，对我国县级及以上医疗机构 青光眼亚专科建设、诊疗设备配备和服务提供情况进行系统整理和统计分析。结果：本次调查覆盖 全国6 341家县级及以上医疗机构，其中设立青光眼亚专科的医疗机构有672家（10.60%）。在青光眼 检查和治疗相关设备中，视力表配置率最高（99.30%），平均每家医疗机构配置3.28台；超声生物显 微镜配置率最低（11.50%），平均每家医疗机构配置0.13台。眼压测量、白内障手术和小梁切开术是 青光眼主要的诊疗服务类型。结论：我国县级及以上医疗机构青光眼亚专科建设亟待加强，诊疗设 备配备不全，诊疗服务能力需要全面提升。     

非小细胞肺癌新辅助靶向及免疫治疗研究进展和展望

肺癌是全球发病率和死亡率最高的恶性肿瘤。近年来,随着新型药物的出现和治疗模式的优化,肺癌患者的预后已有一定改善。新辅助治疗是指对潜在可接受手术切除的患者,先给予术前抗肿瘤治疗后再行手术治疗。新辅助治疗通过术前治疗可以缩小肿瘤体积,降低肿瘤分期;并且可以杀灭患者机体中循环肿瘤细胞及微转移病灶,令患者远期生存获益。靶向治疗及免疫治疗已被应用于晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的一线治疗。因此,有临床试验尝试将以上两种治疗手段应用于早期可切除NSCLC患者的新辅助治疗。本文针对新辅助靶向及免疫治疗对早期可切除NSCLC患者的疗效、治疗中的潜在风险予以综述,并探讨新辅助治疗的未来发展方向。     

基于微信平台的翻转课堂在神经病学教学中的应用

目的　探讨基于微信平台的翻转课堂在神经病学教学中的应用及其效果。方法　以浙江中医药大学滨江学院2014级临床医学专业学生为教学对象，设一班、三班共74名学生为实验组，二班38名学生为对照组。选择周围神经病、神经肌肉-接头疾病为教学内容，实验组采用翻转课堂教学，并利用微信平台进行课前预习、课后复习和互动交流；对照组采用传统教学。两组学生课前和课后分别进行微测试、不记名问卷调查；课程结束后统一进行期末考试，其中包含病例分析题，记录并分析每组学生期末考试和病例分析题成绩。所有数据用SPSS 20.0处理，行t 检验或卡方检验。结果　实验组学生的课后微测试成绩明显高于对照组（P=0.038）；期末考试成绩高于对照组（P=0.046），且期末考试中病例分析题得分高于对照组（P=0.026）。课前问卷调查显示，在学习内容了解程度和预习情况的评价上，实验组选择“良”的学生比例高于对照组（P<0.05）。课后问卷调查显示，实验组在学习兴趣的评价中选择“优”“良”的学生比例均高于对照组（P<0.05）；自学能力评价中选择“良”的学生比例、临床思维能力和教学满意度评价中选择“优”的学生比例均高于对照组（P<0.05）；且实验组在所有项目评价中选择“优”“良”的学生总体比例均高于对照组（P<0.05）。课后实验组学习兴趣评价中选择“优”“良”的学生总体比例高于课前（P<0.01）。结论　基于微信平台的翻转课堂在神经病学教学中的应用可行且有效，可弥补传统教学的不足，有助于提高学生的学习兴趣和自主学习能力、锻炼学生的临床思维，值得推广。