Inhibition of G9a promoted 5-fluorouracil (5-FU) induced gastric cancer cell apoptosis via ROS/JNK signaling pathway in vitro and in vivo

A histone methyltransferase G9a, encoded by euchromatic histone-lysine N-methyltransferase 2 (EHMT2), is up-regulated in various cancers, and is involved in their poor prognosis. In the study reported here, the abnormal expression of G9a in gastric cancer it was investigated in vitro and in vivo. Furthermore, the expression of G9a was revealed to have a negative correlation with chemotherapy response in gastric cancer patients. Next, the effect of G9a knockdown on fluorouracil (5-FU) induced cell apoptosis in gastric cancer cells was focused on. The results demonstrated that G9a knockdown significantly activated the expression level of phospho c-Jun N-terminal kinase (p-JNK) and increased the intracellular reactive oxygen species (ROS) levels in the gastric cancer cells. Inhibition of the ROS/JNK signaling partial reversed the effect of G9a knockdown on 5-FU treated gastric cancer cells. Down-regulation of G9a enhanced the sensitivity of 5-FU to the gastric cancer cells in vitro and in vivo, which was involved in the activation of the ROS/JNK signaling pathway. These results demonstrated that G9a could play a critical role in the sensitivity of chemotherapy for gastric cancer and might be a novel method for treating gastric cancer in the clinic.

A histone methyltransferase G9a, encoded by euchromatic histone-lysine N-methyltransferase 2 (EHMT2), is up-regulated in various cancers, and is involved in their poor prognosis.     

An efficient 3-acylquinoline synthesis from acetophenones and anthranil via C(sp3)–H bond activation mediated by Selectfluor

An efficient method for the synthesis of 3-functionalized quinolines from commercially available acetophenones and anthranil has been described. Selectfluor propels the C(sp³)–H bond activation of the acetophenones and aza-Michael addition of anthranil resulting in annulated 3-acylquinolines in moderate to high yields. DMSO acts not only as a solvent but also as a one carbon donor in the reaction.

An efficient method for the synthesis of 3-functionalized quinolines from acetophenones and anthranil mediated by Selectfluor was achieved.     

人Ⅱ型肿瘤坏死因子受体-免疫球蛋白G1 Fc融合蛋白在糖基工程化毕赤酵母中的表达

目的在糖基工程化毕赤酵母中表达人Ⅱ型肿瘤坏死因子受体-免疫球蛋白G1 Fc融合蛋白（tumor necrosis factor receptor-immunoglobulin G1 Fc fusion,TNFR-Fc）,考察糖基工程化过程对其活性的影响。方法将编码TNFR-Fc的cDNA序列插入毕赤酵母表达载体pPIC6αA中,构建重组表达质粒pPIC6-TF。用表达质粒转染N-糖基化工程改造的毕赤酵母菌株GSB,在含有杀稻瘟菌素的YPD平板上进行筛选。然后再使用HRP标记的羊抗人IgG在醋酸-硝酸纤维素双层膜上进行斑点印迹（dot-blot）筛选。选择表达量较高的工程菌株TNFR-Fc/GSB57进行高密度培养,通过Protein A亲和层析从发酵上清中纯化融合蛋白,利用鼠L929细胞对融合蛋白的抗TNFα活性进行分析。结果通过筛选获得了表达人Ⅱ型肿瘤坏死因子受体-Fc融合蛋白的表达菌株,纯化后的TNFR-Fc融合蛋白拮抗TNFα的EC50高于野生型毕赤酵母表达产物,而低于哺乳动物细胞的表达产物。结论糖基化改造改善了人Ⅱ型肿瘤坏死因子受体-Fc融合蛋白的抗TNFα活性,但必须进行进一步的改造才可能获得与哺乳动物细胞表达产物相似的活性。     

仰卧旋转法治疗腰椎间盘突出症的病例对照研究

目的:比较仰卧位左右旋转作用力和平面作用力手法治疗腰椎间盘突出症的疗效。方法:2008年12月至2011年1月,收治腰椎间盘突出症患者134例,男74例,女60例;年龄17～67岁,50岁以上33例;膨出型9例,突出型74例,游离型51例。134例按随机数字表法分为治疗组(69例)和对照组(65例)。治疗组采用牵引治疗仪持续牵引20min后,用仰卧旋转手法治疗;对照组采用牵引治疗仪20min后,用平面用力推拿手法治疗。隔1d治疗1次,3次为1个疗程。治疗1个疗程后观察患者的症状和体征的积分(包括腰部疼痛与不适、下肢疼痛与麻木、大小便的情况、直腿抬高的水平、下肢行走能力、工作生活情况),并按疗效标准比较2种治疗方法的治疗效果。结果:2组患者均获得随访,时间0.5～2个月,平均1.1个月。治疗组与对照组的症状和体征均较治疗前有明显改善(P<0.01);对照组大小便无力与会阴麻木的症状较治疗前无明显改善(P>0.05)。治疗组69例中,良42例,可20例,差7例;对照组65例中,良20例,可25例,差20例。结论:仰卧位旋转手法治疗腰椎间盘突出症的整体疗效满意,但进行旋转手法操作时力量不宜过重,旋转次数也不宜过多。     

Single-stage anterior debridement and fusion with autografting and internal fixation for pyogenic lumbar spondylodiscitis

Introduction  

Patients with pyogenic lumbar spondylodiscitis can be successfully treated by non-operative methods. However, the typical operation for this condition includes debridement of the infected site, bone grafting and internal fixation to stabilize the spine. Single-stage anterior debridement and fusion with autografting and internal fixation of one spinal segment were performed on nine patients with pyogenic lumbar spondylodiscitis. This operative procedure is rarely documented for pyogenic lumbar spondylodiscitis.     

膝关节骨关节炎内侧间室软骨病损的MRI表现与关节镜术后疗效的相关性研究

目的探讨膝关节骨关节炎（OA）内侧间室软骨病损的MRI表现和关节镜手术后疗效的相关性及膝关节OA的关节镜手术适应证。方法对92例关节镜手术病例,其中男54例,女38例;年龄43～69岁,平均58.5岁。对患者膝关节股骨内髁和胫骨内侧平台软骨的MRI表现按ICRSMR分级标准进行分级,对所有患者均进行了术后12～30个月的随访,随访时进行Lysholm评分。结果 92例92个膝关节,核磁共振显示关节软骨损伤Ⅳ级10例;Ⅲ级16例;Ⅱ级20例;Ⅰ级25例;0级21例,分级的均数为（1.66±1.303）;术后Lysholm评分最高100分;最低64分,评分的均数（95.42±7.398）。术后Lysholm评分与ICRSMR分级相关系数r=-0.672,P〈0.05,统计学处理呈负相关。结论认为术前膝关节内侧间室软骨的MRI（1.5T）分级对膝关节OA关节镜手术指征的判断有重要的参考价值。     

Influence of angiotensin II type 1 receptor-associated protein on prenatal development and adult hypertension after maternal dietary protein restriction during pregnancy

An adverse relationship between suboptimal fetal environments and the development of adult diseases, such as hypertension, type II diabetes, and cardiovascular disease, has been reported in numerous studies. The purpose of this study was to investigate the strain difference of offspring’s response to maternal malnutrition during pregnancy and the involvement of the renin-angiotensin system (RAS) in the development of adult hypertension using C57BL/6J (C57) mice and angiotensin II (Ang II) type 1 receptor-associated protein-transgenic (ATRAP-Tg) mice. Pregnant dams were fed an isocaloric diet containing either 20% (normal protein; NP) or 8% (low protein; LP) protein. Birth weight was significantly reduced in C57-LP offspring, but not in ATRAP-Tg-LP offspring. Arterial blood pressure was higher in C57-LP offspring than in the other groups. In contrast, ATRAP-Tg-LP offspring did not show an increase in blood pressure compared with NP offspring. Renal angiotensin II type 1 (AT₁) receptor expression was not altered by maternal malnutrition, whereas angiotensin II type 2 receptor expression was significantly decreased in C57-LP offspring. In conclusion, these findings suggest that a suboptimal intrauterine environment induces adult hypertension because of an alteration of expression of RAS components, which was partly suppressed by sustained ATRAP overexpression via attenuation of the AT₁ receptor-mediated pathological response.     

Prognostic factors before and after recurrence of resected non-small cell lung cancer

BackgroundThe post-surgical follow-up strategy in non-small cell lung cancer (NSCLC) is still controversial. Data on factors that affect the interval between surgery and recurrence or predict survival after recurrence in NSCLC patients are still limited.MethodsFrom a group of 775 NSCLC patients who consecutively underwent curative surgery, 133 patients showing recurrence were retrospectively analyzed.ResultsRecurrence was most often seen in smokers and patients with advanced stage disease. In patients experiencing relapse, the 1- and 2-year recurrence rates were 58% and 84%, respectively. A multivariate analysis showed that patients who underwent limited surgery, had non-adenocarcinoma disease, or had metastatic lymph node involvement showed early recurrence (p-values: <0.01, 0.04, and 0.04, respectively). Among all relapsed patients, the 2-year overall survival rate after recurrence was 37%. A multivariate analysis demonstrated that patients with lymph node metastasis at the time of surgery and patients who experienced early recurrence were significantly more likely to have a shorter survival time after recurrence (hazard ratio, 1.73; p=0.03; hazard ratio, 2.56; p<0.001, respectively).ConclusionsPatients who are node-positive, show non-adenocarcinoma disease, and/or undergo limited surgery should receive careful follow-up during the first year after surgery for NSCLC. The present data provide additional information about postoperative recurrence in NSCLC patients.