RNAi screening with shRNAs against histone methylation-related genes reveals determinants of sorafenib sensitivity in hepatocellular carcinoma cells

Sorafenib is the first drug currently approved to treat advanced hepatocellular carcinoma (HCC). However, very low response rate and acquired drug resistance makes rare patients benefit from sorafenib therapy, therefore it is urgent to find biomarkers for sorafenib sensitivity. Histone modifications, including histone methylation, have been demonstrated to influence the initiation and progression of HCC. It is of great interest to elicit the possibility whether histone methylation plays a role in regulation of sorafenib sensitivity. In present work, a high throughput RNAi screening with 176 shRNA pools against 88 histone methyltransferases (HMTs) and histone demethyltransferases genes was applied to HepG2 cells. Silencing of 3 genes (ASH1L, C17ORF49 and SETD4) was validated to specifically promote HepG2 cells sensitivity to sorafenib. Western blotting results showed that those 3 HMT genes knockdown alone or sorafenib treatments alone both induce AKT/ERK activation. However, combination treatment with sorafenib and silencing of C17ORF49 or SETD4 downregulated AKT phosphorylation and hence induced HCC cells death. Our work may provide potential biomarkers for sorafenib sensitivity and therapeutic combination for sorafenib treatment in HCC patients.     

肺瘤平Ⅱ号对Lewis肺癌小鼠瘤细胞CD44V6及CD49表达的影响*

目的:研究中药复方制剂肺瘤平Ⅱ号对Lewis肺癌小鼠移植瘤细胞CD44V6及CD49表达的影响,探讨肺瘤平Ⅱ号抗肿瘤的作用机制。方法:60只C57BL/6近交系小鼠右腋皮下接种Lewis瘤细胞悬液0.2 mL,随机分为生理氯化钠溶液对照组、环磷酰胺(CTX,60 mg.kg-1,ip)组、榄香烯组(65 mg.kg-1,ip,qd)、参一胶囊组(5 mg.kg-1,ig,qd)、肺瘤平Ⅱ号高、低剂量组(10,2.5 g.kg-1,ig,qd),每组10只。实验d 2开始给药,除CTX组给药1 d外,其余各组均给药12 d。实验d14以流式细胞仪检测各组小鼠移植瘤组织中瘤细胞CD44V6及CD49的表达。结果:与生理氯化钠溶液对照组比较,肺瘤平Ⅱ号高、低剂量组瘤细胞中CD44V6和CD49表达均显著降低(CD44V6:12.04±2.05 vs.8.44±1.57,8.23±2.05;CD49:59.07±7.78 vs.46.96±2.63,51.81±6.54;P<0.05或P<0.01)。结论:肺瘤平Ⅱ号通过抑制肿瘤细胞CD44V6和CD49的表达,可能是其抗肿瘤作用机制之一。     

补肾生血法对慢性再生障碍性贫血患者骨髓单个核细胞粘附分子VLA-5/CD49e表达水平的影响

目的:探讨补肾生血法对慢性再生障碍性贫血(简称慢性再障,Chronic Aplastic Anemia CAA)患者的粘附分子VLA-5/CD_(49e)表达水平的影响。方法:将45例慢性再障患者随机分为补髓生血颗粒组(实验组)和再障生血片组(对照组),采用流式细胞术(FCM)检测实验组和对照组慢性再障患者治疗前后骨髓单个核细胞相关整合素VLA亚家族粘附分子VLA-5/CD_(49e)的抗原表达水平并进行比较分析。结果:CAA患者骨髓单个核细胞粘附分子VLA-5/CD_(49e)处于低表达状态,疗后实验组和对照组表达水平均有所恢复,但组间差异显著,组内治疗前后差异显著,但与正常组比较仍有显著性差异,疗后VLA-5/ CD_(49e)表达阳虚与阴虚无显著差异。结论:慢性再障患者骨髓单个核细胞粘附分子VLA-5/CD_(49e)表达水平异常,它有可能是CAA造血微环境粘附造血异常调控的因素之一。     

In vitro interactions of agonists and antagonists with beta-adrenergic receptors

Neurotransmitters and hormones mediate their effects through interaction with specific receptors. A complete understanding of the effects of these chemical signals requires detailed knowledge, at the molecular level, of agonist/receptor interactions. It is likely that agonists and antagonists interact with the same site on a receptor. Agonists, however, are by definition different from antagonists in that agonists are responsible for transducing information across the cell membrane, ultimately resulting in a biological response, while antagonists appear to act through passive occupancy of receptors. Implicit in this concept is the idea that these fundamental differences between agonists and antagonists arise from the sequelae induced by agonist-specific interactions with receptors.     

Advanced early and late atrioventricular block in acute inferior wall myocardial infarction

Seventy-six patients with acute inferior acute myocardial infarction (AMI) and advanced atrioventricular (AV) block are described. According to pre-established ECG criteria and time of appearance of the advanced AV block, patients were divided into two groups. The early block group consisted of 31 patients who developed advanced AV block during the hyperacute ECG stage of AMI. Advanced AV block in these patients was characterized by early appearance, short duration, third-degree type block, poor response to atropine, and increased need for pacemaker therapy. The late block group consisted of 45 patients who developed advanced AV block during subsequent ECG stages of AMI. Advanced AV block in these patients was characterized by late appearance, longer duration, second-degree type block, positive response to atropine, and diminished need for pacemaker therapy. Morbidity and mortality also differed between both groups. Patients with early block had more syncope (32% vs 2%, p < 0.0001), more left heart failure (36 vs 7%, p < 0.005), and more cardiogenic shock (39% vs 2%, p < 0.001) than patients with late block. The mortality rate in the early block group was high (23%) and similar to that reported in the literature, whereas the mortality rate in the late block group was low (7%, p < 0.05) and similar to the mortality rate reported for acute inferior AMI without advanced AV block. These data identify a subgroup of patients with acute inferior AMI and advanced AV block, which accounts for the high mortality rate reported in this group of patients.     

Sleep microstructure and neurodegeneration as measured by [<Superscript>123</Superscript>I]β-CIT SPECT in treated patients with Parkinson’s disease

Abstract Objectives Along with spindles, K-complexes are well known hallmarks of stage 2 (S2) sleep. However, little is known about their quantity in S2 sleep of patients with Parkinsons disease (PD). Setting Sleep laboratory, Department of Neurology, University of Vienna, Austria. Patients and methods Whole-night polysomnography (PSG) was performed in twelve treated PD patients and ten healthy controls without history of sleep complaints. The quantity of spontaneous K-complexes, K-alpha-complexes, and sleep spindles in one hour S2 sleep, distributed in four epochs of 15 minutes all through the night, were visually selected and analysed. The quantity and the temporal course of these phasic events were compared with the quantity in age-matched healthy controls. Nine of the twelve PD patients underwent [¹²³I]-CIT SPECT for calculating dopamine transporter binding in the striatum and serotonin transporter density in the thalamus-hypothalamus region. Results There was no difference between the quantity of K-complexes, K-alpha-complexes, and sleep spindles in PD patients and in the healthy control group. K-complexes but not sleep spindles decreased over the night in both groups. The number of sleep spindles did not correlate with the dopamine transporter binding in the striatum or the serotonin binding in the thalamic/hypothalamic region. Conclusion K-complexes and sleep spindles are not reduced and do not seem to be related to the degree of dopaminergic degeneration in treated PD patients.This research was supported in part by the European Commission, DG XII (Project Biomed-2 BMH4-CT97–2040 SIESTA) and by the Austrian National Bank (Project 7870). Svenja Happe, MD, was recipient for a fellowship stipend of the European Neurological Society (ENS).     

Onset of oscillopsia after visual maturation in patients with congenital nystagmus1

Purpose

To describe the clinical and oculographic characteristics of a cohort of five patients with congenital nystagmus (CN) and late-onset oscillopsia caused by a coincidental decline in other visual and/or ocular motor functions.

武功演员肩部损伤的治疗

武功演员（包括戏曲武功演员、杂技顶功演员,舞蹈顶尖演员等）最常见的损伤是肩部损伤,而肩部损伤最常见的是肩峰、肩袖、肩肌群的慢性损伤。１　病因机理武功演员双手倒立、拿顶、前翻、后滚、纵跳、穿毛、投抱、弄剑、阻击、对打、无不以肩部动作为主导,肩部的肌肉群在多次的反复动作,特别是肱二头肌肌腱结节及冈上肌、冈下肌起止点受到机械刺激,加上慢性劳损兼受风寒湿的侵袭,使局部气血瘀滞,肌腱群与肌腱腔增粗、变性,亦使纤维管腔变窄变细,从而使肌腱在管内的滑动受到影响,而产生肩部的╥、胀、痛、麻的临床症状,甚者发生肩…