The effect of caffeine abstinence on sleep among habitual caffeine users with poor sleep

Caffeine is the most widely used psychoactive substance in the world and is known to disrupt healthy sleep. However, very few studies have directly tested the effect of caffeine abstinence on sleep, and these have yielded inconsistent findings. The purpose of the present study was to examine changes in sleep following caffeine abstinence and examine the extent to which characteristics of habitual caffeine use moderated this change. Participants included 66 healthy, young adults with habitual caffeine use and poor sleep. During the 2‐week baseline, sleep was assessed using wrist actigraphy and daily caffeine use was assessed with bedtime diaries. Eligible participants then completed 1 week of caffeine abstinence, during which sleep was measured with wrist actigraphy. Multilevel models found no significant differences between either mean levels or growth trajectories of total sleep time or sleep efficiency between baseline and caffeine abstinence. Mean levels of sleep onset latency also did not differ between baseline and caffeine abstinence. A small but significant quadratic effect was observed, such that sleep onset latency decreased during the first few days of caffeine abstinence, then increased to levels above baseline. Characteristics of caffeine use did not moderate changes in sleep between baseline and caffeine abstinence. These data suggest that abstaining from caffeine may not result in long‐term sleep improvement for habitual caffeine users, which contradicts the common sleep health recommendation. The present findings encourage more rigorous investigation of the effectiveness of caffeine restriction on sleep.     

Association of job stress,CLOCK gene polymorphism and their interaction with poor sleep quality

Job stress and the Circadian Locomotor Output Cycles Kaput (CLOCK) gene could affect circadian rhythm and sleep quality. The main aim of our present study was to investigate the association of job stress, CLOCK gene polymorphism and their interaction with sleep quality in a non‐clinical Chinese Han population, which has not been reported to date. Using a cross‐sectional design, 450 subjects were recruited in Beijing. Sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI) and job stress was measured with the Work Stress Scale. CLOCK gene rs11932595 polymorphism was genotyped in 297 blood samples. Correlation analysis showed a close but different association of high job stress with the PSQI and its components. Analysis of variance showed significant main effects of the CLOCK gene rs11932595 polymorphism. G‐allele carriers had a higher score in the PSQI, sleep duration, sleep latency and sleep disturbances. Further interaction analyses showed an ordinal interaction on sleep duration, and a disordinal interaction on daytime dysfunction. Specifically, G‐allele carriers had poorer sleep duration than AA homozygotes when in high job stress, while the two subgroups displayed similar sleep duration when in low job stress, conforming to the diathesis–stress model. In comparison to G‐allele carriers, AA homozygotes experienced less daytime dysfunction when in low job stress whereas more daytime dysfunction when in high job stress, fitting with the differential susceptibility model. As genetic links have been revealed, our investigation might be conducive for elucidating aetiological factors for sleep quality and targets for implementing interventions to attain good sleep quality.     

LY3214996 relieves acquired resistance to sorafenib in hepatocellular carcinoma cells

Background: Sorafenib, an oral multi-kinase inhibitor of rapidly accelerated fibrosarcoma; vascular endothelial growth factor receptor-2/3, platelet-derived growth factor receptor, c-Kit, and Flt-3 signaling, is approved for treatment of advanced hepatocellular carcinoma (HCC). However, the benefit of sorafenib is often diminished because of acquired resistance through the reactivation of ERK signaling in sorafenib-resistant HCC cells. In this work, we investigated whether adding LY3214996, a selective ERK1/2 inhibitor, to sorafenib would increase the anti-tumor effectiveness of sorafenib to HCC cells.Methods: The Huh7 cell line was used as a cell model for treatment with sorafenib, LY3214996, and their combination. Phosphorylation of the key kinases in the Ras/Raf/MAPK and PI3K/Akt pathways, protein expression of the cell cycle, and apoptosis migration were assessed with western blot. MTT and colony-formation assays were used to evaluate cell proliferation. Wound-healing assay was used to assess cell migration. Cell cycle and apoptosis analyses were conducted with flow cytometry.Results: LY3214996 decreased phosphorylation of the Ras/Raf/MAPK and PI3K/Akt pathways, including p-c-Raf, p-P90RSK, p-S6K and p-eIF4EBP1 activated by sorafenib, despite increased p-ERK1/2 levels. LY3214996 increased the anti-proliferation, anti-migration, cell-cycle progression, and pro-apoptotic effects of sorafenib on Huh7^R cells.Conclusions: Reactivation of ERK1/2 appears to be a molecular mechanism of acquired resistance of HCC to sorafenib. LY3214996 combined with sorafenib enhanced the anti-tumor effects of sorafenib in HCC. These findings form a theoretical basis for trial of LY3214996 combined with sorafenib as second-line treatment of sorafenib-resistant in advanced HCC.     

基于CT图像的评分模型预测食管鳞癌喉返神经旁淋巴结转移风险

目的:基于原发肿瘤及淋巴结CT特征建立评分模型预测食管鳞癌患者喉返神经旁淋巴结(RLN-LN)转移风险。方法:回顾性收集2014年1月至2019年12月于北京大学肿瘤医院行食管癌根治术并清扫RLN-LN的92例食管鳞癌患者。根据术后淋巴结病理结果分为RLN-LN转移组(n=37)和非转移组(n=55)。评估术前CT图像,记录食管癌患者年龄、性别、分化程度、肿瘤位置、肿瘤大小(肿瘤长度、肿瘤厚度、厚度/长度)、RLN-LN大小(淋巴结短径、长径、短径/多平面重建(MPR)最长径]。采用多元logistic回归筛选独立预测因子并建立评分模型,采用ROC曲线评估评分模型及独立预测因子诊断RLN-LN转移的效能,采用Z检验比较曲线下面积(AUC)的差异。应用Hosmer-Lemeshow检验和校准曲线评估模型拟合度。结果:肿瘤位置、肿瘤长度、RLN-LN短径、短径/MPR最长径是RLN-LN转移的独立预测因子,其诊断RLN-LN转移的AUC分别为0.586、0.705、0.831、0.777。基于以上4个CT特征建立评分模型,评分模型诊断RLN-LN转移的AUC为0.903(95%CI 0.846~0.959),优于各单一CT特征(Z=5.812,P<0.001;Z=2.161,P=0.030;Z=2.929,P=0.003;Z=4.052,P<0.001)。拟合优度Hosmer-Lemeshow检验结果显示P=0.555,校准曲线提示评分模型预测RLN-LN转移风险与实际转移风险之间具有良好的一致性。结论:基于CT图像的评分模型有助于食管鳞癌RLN-LN转移状态危险分层。     

新冠疫情背景下组织学与胚胎学网络教学的实施及教学反思*

2020年1月,突发的新冠肺炎疫情给我国经济社会发展带来巨大的挑战,能否将信息技术和网络教学完美融合,确保网络教学的质量,是摆在每一位教育工作者面前的问题[1].按照国家关于新型冠状病毒肺炎疫情防控工作部署要求,遵循"停课不停教、停课不停学"的原则,在2020年春季学期面向本校中医学、针灸推拿学、临床医学等专业开设组织学与胚胎学课程的网络教学.组织学与胚胎学是医学院校中非常重要的专业基础课,与现代医学及生命科学相互交叉与渗透,该学科研究的是正常人体的微观结构及功能,具有教学内容多、知识点繁杂、专业术语多、教学学时偏少、学生学习难度较高等特点[2].     

成人朗格汉斯细胞组织细胞增生症的诊疗

朗格汉斯细胞组织细胞增生症(LCH)是一种以MAPK信号通路激活为主要特征的克隆性血液系统肿瘤,属于炎性髓系肿瘤。其临床表现多样,最常见的临床受累脏器为骨骼、肺、垂体等。其主要依赖于病理活检确诊,病理免疫组化CD207和电镜检查可见伯贝克颗粒是诊断的金标准。根据临床受累脏器范围,LCH分为单系统单病灶、单系统多病灶、多系统受累。治疗主要根据临床分型,对于单系统单病灶患者以局部治疗为主,对于单系统多病灶或多系统LCH以全身治疗为主。     

从中医“阳气亏虚，痰瘀内阻”理论探讨中医药防治心肌缺血再灌注损伤的机制＊

目的 从文献探讨中医“阳气亏虚，痰瘀内阻”理论防治急性心肌梗死（Acute myocardial infarction，AMI）后心肌缺血再灌注损伤（Myocardial ischemia reperfusion injury，MIRI）的机制，为其科研及防治提供依据。方法 检索中国知网数据库、万方数据库、NCBI数据库从建库到2020年6月14日有关MIRI的文献，总结MIRI的发病机制及中医证治的新观点，分析可信度较高的相关实验数据，对运用中医“阳气亏虚，痰瘀内阻”理论防治MIRI进行探讨。结果 文献表明温阳化气、活血化瘀、祛痰化浊的中医方药可通过抑制细胞内Ca²⁺超载，稳定线细胞膜，减少氧自由基的生成，改善细胞能量代谢等多条途径参与缺血心肌的保护作用。结论 MIRI的发病机制文献表明，涉及多种病因，中医药可通过多靶点、多路径参与对MIRI的防治，且可能对MIRI的临床辨证论治提供理论依据。     

构建靶向血管内皮生长因子受体2可调控活性的嵌合抗原受体T细胞及其体外功能验证

目的构建靶向血管内皮生长因子受体2(VEGFR2)可调控活性的小分子门控嵌合抗原受体T(smgCAR-T)细胞系统并在体外验证其抗肿瘤和可调节活性。方法采用基因全长合成和磷酸钙转染法构建smgCAR-T及其阳性(CAR+-T)和阴性(CAR--T)对照细胞。同时构建表达VEGFR2的小鼠结直肠癌细胞(MCA38VEGFR2+)。验证并筛选构建成功的细胞后再体外验证CAR-T细胞靶向结合能力。在不同的效靶比下检测白细胞介素-2和肿瘤坏死因子-γ的浓度来评估CAR-T细胞的体外分泌功能,用乳酸脱氢酶浓度评估CAR-T细胞的体外抗肿瘤活性。组间的比较采用t检验或单因素方差分析。结果基因测序和流式细胞术证实CAR-T细胞和靶细胞构建成功。与对照组比较,CAR+-T细胞+MCA38VEGFR2+组具有最强的靶细胞杀伤能力。在smgCAR-T细胞+MCA38VEGFR2+组中,随着C16-(S)-3-甲基吲哚雷帕霉素(Rapalog)滴度升高靶细胞杀伤率逐渐升高;当Rapalog为40 nmol/L时杀伤率达到最大值,为(66.25±13.20)%。分别向smgCAR-T细胞+MCA38VEGFR2+细胞组(A和B组)加入40 nmol/L的Rapalog后,在24 h时可观察到两组杀伤率出现同步升高[(44.25±6.24)%比(49.25±5.56)%,t=1.197,P>0.05],差异无统计学意义。在置换培养基后,再次添加了Rapalog的A组中观察到靶细胞杀伤率升高明显;而未再次添加Rapalog的B组中靶细胞杀伤率升高缓慢;此时,A和B组杀伤率差异有统计学意义[(89.00±3.16)%比(56.50±6.61)%,t=8.873,P<0.01]。结论构建的smgCAR-T细胞在体外展现出一定的抗肿瘤活性,且其活性受小分子化合物Rapalog的可逆调控。