eIF4EBP3 was downregulated by methylation and acted as a tumor suppressor by targeting eIF4E/β-catenin in gastric cancer

Gastric Cancer - Epigenetic aberrations of tumor suppressor genes (TSGs), particularly DNA methylation, are frequently involved in the pathogenesis of gastric cancer (GC). Through a methylome...     

CTA诊断右下肺叶基底段异常体动脉供血1例

患者男,22岁,无明显诱因咳嗽、痰中带血1周,起初干咳,后咳痰并痰中带血,偶咯出少量暗红色血液;无发热、盗汗、乏力,无胸闷、胸痛及呼吸困难,平素体健,无家族病史。查体:双肺呼吸音稍粗,右肺下叶闻及细湿啰音。胸部增强CT:右肺下叶基底段见片状磨玻璃影,内见直径约8mm粗大供血动脉自腹腔干发出;支气管树分支及肺发育正常,未见隔离肺(图1A^1C)。肺动脉CTA示右下肺基底段动脉部分缺如(图1D),考虑为右下肺异常体动脉供血并周围肺组织肺泡出血可能。     

依维莫司联合全反式维甲酸逆转急性早幼粒细胞白血病细胞耐药的研究

目的探讨依维莫司联合全反式维甲酸(简称维甲酸)逆转急性早幼粒细胞白血病(APL)细胞株NB4-R1耐药的作用。方法应用CD11b染色流式细胞术及硝基四唑氮蓝(NBT)还原实验检测两药联合应用对细胞分化的影响, 流式细胞术检测细胞周期情况, Annexin V/PI双染色检测细胞凋亡情况, 蛋白质印迹法检测自噬相关蛋白微管结合蛋白轻链3(LC3)、Beclin 1及早幼粒白血病-维甲酸受体融合蛋白(PML-RARα)、磷酸化核糖体S6激酶(P-P70S6K)、磷酸化4E结合蛋白1(P-4E-BP1) 等表达水平。结果与维甲酸组比较, 联用组能诱导耐药细胞株NB4-R1细胞的分化, 并将细胞增殖阻止在G ₁期而对细胞凋亡无明显影响。100 nmol/L依维莫司组、1μmol/L维甲酸组、联用组、对照组NB4-R1细胞培养48 h后分化百分率分别为(2.29±0.57)%、(17.06±2.65)%、(54.47±4.91)%、(2.54±0.53)%; 处于G ₁期的细胞百分率分别为(35.20±11.97)%、(33.54±6.25)%、(53.70±8.73)%、(27.40±6.01)%; 四组细胞凋亡细胞百分率分别为(2.30±0.14)%、(2.25±0.21)%、(2.40±0.28)%、(1.95±0.07)%。与维甲酸组比较, 联用组mTOR信号通路下游的P70S6K、4E-BP1分子磷酸化水平下降, LC3-II和Beclin 1的表达上调, 且能部分降解融合蛋白PML-RARα。 结论依维莫司联合维甲酸能诱导NB4-R1细胞分化, 且能阻滞细胞周期而不致细胞凋亡, 其机制可能与依维莫司联合维甲酸抑制mTOR信号通路激活自噬作用从而降解PML-RARα蛋白有关。     

两例 SMILE 术中特殊情况更改 SBK 手术的疗效观察

目的：通过对同一患者双眼不同手术方式的自身对比，了解飞秒扫描后改SBK手术的疗效差异，为不同患者屈光手术方式的选择提供临床指导依据。方法回顾分析2例右眼行飞秒激光小切口透镜取出术（ SMILE），左眼SMILE术中负压环脱失和激光扫描不良透镜分离困难而改行机械刀制瓣准分子激光手术（ SBK）的患者，比较术后视力、等效球镜（ SE）、对比敏感度（ CSF）、波前像差（ HAOS）以及泪膜破裂时间（ BUT）、泪液分泌功能试验（ Schimer I）和SPEED、OSDI干眼症状问卷调查分析差异。结果（1）术后个月，均能达到最佳矫正视力（BSCVA），等效球镜均在±0．75 D以内，双眼比较无显著性差异。（2）CSF的比较，左右眼无显著性差异，略低于正常水平。（3）术后3个月，BUT和Schimer检查中，双眼无显著性差异。（4）HAOS比较中，总像差RMS和高阶像差这两项， SMILE眼低于SBK眼；球差（S）的比较，SMILE眼高于SBK眼。（5）SPEED和OSDI问卷评分双眼无显著差异。结论 SMILE失败眼改SBK后视觉质量与SMILE眼无显著差异，其视觉质量、疗效不受影响。     

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.