黄芪多糖对人鼻咽癌CNE-1细胞的放疗增敏及上皮间质转化的作用

目的:采用黄芪多糖(APS)与放射治疗(IR)联用,研究APS对人鼻咽癌CNE-1细胞的放疗敏感性及上皮间质转化(EMT)的作用机制。方法:采用细胞计数(CCK-8)法检测不同质量浓度APS(0,6.25,12.5,25,50,100,200 g·L-1)对CNE-1细胞的细胞毒性;克隆形成实验计算12.5 g·L-1APS与不同放射剂量(0,2,4,6 Gy)联用后对CNE-1细胞的存活分数(SF),利用线性二次方程数学模型(LQ)根据SF值绘制放射敏感曲线;细胞划痕和transwell小室实验分别检测各组细胞的迁移和侵袭能力;流式细胞仪检测各组细胞的凋亡情况;蛋白免疫印迹法(Western blot)检测各组细胞的EMT标记物、凋亡标记物以及蛋白激酶B/细胞外调节蛋白激酶(Akt/ERK)通路蛋白的表达水平。结果:克隆形成实验和放射敏感曲线结果表明,非毒性剂量12.5 g·L-1APS与4 Gy放射剂量联合给药可以明显增加CNE-1细胞的放疗敏感性;与空白组及IR组比较,APS与IR联用可以抑制CNE-1细胞的迁移和侵袭能力(P0.05),明显增加CNE-1细胞的凋亡率(P0.05)。与空白组及IR组比较,APS与IR联用可以显著下调间质型钙黏蛋白(N-cadherin),p-Akt和p-ERK蛋白表达水平,明显上调上皮型钙黏蛋白(E-cadherin),B淋巴细胞瘤-2相关X蛋白(Bax)和半胱天冬氨酸蛋白酶-3(Caspase-3)蛋白表达水平(P0.05)。结论:APS与IR联用可以抑制CNE-1细胞的迁移和侵袭,增加放疗引起的细胞凋亡,其可能通过抑制EMT和Akt/ERK通路有关。     

Effect of Exposure to Agent Orange on the Risk of Monoclonal Gammopathy and Subsequent Transformation to Multiple Myeloma: A Single-Center Experience From the Veterans Affairs Hospital,Detroit

BackgroundMonoclonal gammopathy of undetermined significance (MGUS) is an indolent, premalignant plasma cell disorder with the potential of transforming into symptomatic multiple myeloma (MM). There are multiple risk factors that contribute to transformation. Agent Orange (AO) has been linked with multiple malignant and nonmalignant conditions.Patients and MethodsWe conducted a retrospective chart review of patients with monoclonal gammopathy who were seen at John D. Dingell Veterans Affairs Medical Center (Detroit, Michigan) between 2005 and 2015 with MGUS, smoldering multiple myeloma, and MM. We explored baseline patient characteristics and explored AO exposure. Dates of diagnosis, dates of progression, and expiration dates were recorded to time to progression and overall survival (OS).ResultsWe identified 211 patients with monoclonal gammopathy; 96% were male and 122 were African American. Eleven patients had reported AO exposure. Cumulative risk of progression in the overall population was 1.4% at 1 year. Risk of transformation in the population exposed to AO was significantly higher with a hazard ratio (HR) of 11.19 (95% confidence interval [CI], 2.10-59.47; P = .005). OS was numerically shorter in AO-exposed patients with a median OS of 7 years compared with 11.1 years in those not exposed. However, AO exposure was not associated with OS in multivariable analysis (HR, 0.50; 95% CI, 0.07-3.83; P = .508).ConclusionMonoclonal gammopathy is a premalignant condition with the risk of progressing to MM. Exposure to AO has been implicated in multiple conditions including MM. Our study demonstrates an increased risk of progression in exposed patients.     

E-cadherin在妇科三大恶性肿瘤中表达的意义及研究进展

E-钙黏蛋白（E-cadherin）是一种主要存在于人和动物上皮的黏附分子，主要功能是维持正常上皮细胞形态和结构完整性。现已在多种肿瘤研究中发现，E-cadherin表达的下调，极易造成肿瘤细胞向外周组织发生浸润和远端转移，但与E-cadherin相关研究在妇科恶性肿瘤中进展缓慢，E-cadherin在子宫内膜癌、卵巢癌和宫颈癌病变过程的调控机制尚不完全清楚，而且肿瘤的发生和发展是多因素作用的过程，需要进一步加强研究，该文章就 E-cadherin在妇科三大妇科恶性肿瘤中表达的意义及研究进展进行综述。     

天麻素生物合成的研究进展

天麻素是我国名贵中药材天麻中的一种主要活性成分，具有降血压、抗癫痫、抑制肿瘤、保护神经等多方面的药理活性。随着市场对天麻素需求的不断增长以及传统获取方法固有的问题，导致急需新的方法来解决天麻素生产实际中面临的各项困难。生物合成法是一种有别于传统获取法的新方法，已在天麻素获取上取得了较大进展和成果，故现阶段有必要从天麻素生物合成途径、植物转化法和微生物转化法3个方面，对天麻素生物合成进行系统地阐述，从而为进一步改进和完善天麻素生产方法，以满足人们对其不断增长的需求提供有价值的参考。     

PP4R1 interacts with HMGA2 to promote non-small-cell lung cancer migration and metastasis via activating MAPK/ERK-induced epithelial-mesenchymal transition

Protein phosphatase 4 regulatory subunit 1 (PP4R1) has been shown to play a role in the regulation of centrosome maturation, apoptosis, DNA repair, and tumor necrosis factor signaling. However, the function of PP4R1 in non-small-cell lung cancer remains unclear. In this study, we identify PP4R1 as an oncogene through Oncomine database mining and immunohistochemical staining, and we showed that PP4R1 is upregulated in lung cancer tissues as compared with that in normal lung tissues and correlated with a poor prognosis in lung cancer patients. Furthermore, in vitro study by wound-healing and Transwell assay showed that PP4R1 could promote migration and invasion of lung cancer cells. Mechanistic investigations revealed that PP4R1 could cooperate with high mobility group AT-hook 2 and thereby promotes epithelial-mesenchymal transition via MAPK/extracellular receptor kinase activation. Taken together, our study provides a rich resource for understanding PP4R1 in lung cancer and indicates that PP4R1 may serve as a potential biomarker in lung cancer therapies.     

生理学教学核心理念变革的探讨

医学教育改革更多的是热衷于授课形式和方法的改革，而忽视了真正能够渗透到教学各方面的教学理念的改革。结合对生理学教学目标的反思和“岗位胜任力”培养的需求，将生理学教学的核心理念总结为四个方面：“三观”要正，帮助学生树立平衡观、辩证观和整体观；“三基”要牢，培养学生掌握基本的知识架构体系、基本的知识获取能力、基本的操作技能；重视学以致用和强化人文素养。上述核心理念在教学实践中得到学生的广泛认可，临床医学专业学生对核心理念的评价明显高于护理专业。下一步教学改革的方向是在教学理念的指导下如何细化授课内容，以适应专业设置越来越细化的现状。     

＊ 补充基金信息（立项部门，项目类型，课题名称，负责人信息）

病机是认识疾病病变的关键，抓住核心病机演变发展的规律，是中医临床诊疗的主旨和核心。病机兼化理论由中国中医科学院胡镜清研究员提出，用以从病机层面理解疑难复杂疾病病证关系和把握其演变规律，在明确疾病基本矛盾的同时，兼顾疾病的复杂性和多变性。文章通过构建新型冠状病毒肺炎病机兼化框架，揭示其病机演化规律，认为新冠肺炎属于“湿毒疫”范畴，湿毒始终是本病的病变核心，初期寒化，进展期热化，恢复期虚化是本病病机的传变方式。知本病之机，可未病先防，知病机传变，可截断扭转，有利于临床上增强对疾病发生发展趋势的预见性。