Immune regulation by low doses of the DNA methyltransferase inhibitor 5-azacitidine in common human epithelial cancers

Epigenetic therapy is emerging as a potential therapy for solid tumors. To investigate its mechanism of action, we performed integrative expression and methylation analysis of 63 cancer cell lines (breast, colorectal, and ovarian) after treatment with the DNA methyltransferase inhibitor 5-azacitidine (AZA). Gene Set Enrichment Analysis demonstrated significant enrichment for immunomodulatory pathways in all three cancers (14.4-31.3%) including interferon signaling, antigen processing and presentation, and cytokines/chemokines. Strong upregulation of cancer testis antigens was also observed. An AZA IMmune gene set (AIMs) derived from the union of these immunomodulatory pathway genes classified primary tumors from all three types into “high” and “low” AIM gene expression subsets in tumor expression data from both TCGA and GEO. Samples from selected patient biopsies showed upregulation of AIM genes after treatment with epigenetic therapy. These results point to a broad immune stimulatory role for DNA demethylating drugs in multiple cancers.     

肺腺癌中关键lncRNA的表达及免疫相关分析

目的:通过鉴定与肺腺癌（LUAD）预后相关的长非编码RNA（lncRNA）,研究LUAD的发生机制及其预后意义,确定与LUAD预后相关的敏感性生物标志物,并对其进行免疫途径相关性分析。方法:从肿瘤基因组图谱数据库(TCGA)中获取与LUAD相关的数据,通过单因素Cox回归分析及套索算法（LASSO）筛选lncRNA,使用多因素Cox回归进行预后风险评分分析,建立预后风险模型,用计算曲线下面积（AUC）和Kaplan-Meier（K-M）生存分析方法评价模型的稳健性和准确性。利用K-M生存分析方法确定与生存状态相关的潜在生物标志物,并通过ImmLnc平台对其进行免疫途径相关性研究。结果:从49个与生存相关的lncRNAs中确定了12个预后相关生物标志物,通过K-M生存分析,MIR34AHG和PRKCA-AS1被确定为与预后相关的生物标志物(P＜0.05)。模型的3年和5年生存率的AUC分别为0.82和0.846。与MIR34AHG相关的免疫途径分别为“细胞因子受体”(P＜0.05),“抗原处理和提呈”(P＜0.05),与PRKCA-AS1相关的免疫途径为“抗原处理和提呈”(P＜0.05)。结论:通过对生物信息大数据的分析,我们确定了两个关键lncRNAs及其相关的免疫途径,为LUAD的预后评估提供了新的生物标志物。     

性别对肥胖哮喘患儿吸入糖皮质激素后肺功能的影响

目的研究性别对肥胖哮喘患儿吸入糖皮质激素（ICS）治疗前后肺功能的影响。方法190例哮喘患儿根据性别分为男性 组（102例,正常体质量组/肥胖组57/45）、女性组（88例正常体质量组/肥胖组46/42）,检测所有患儿治疗前及规范化ICS治疗1 年后肺功能,包括第1秒时间肺活量（FEV1）、用力肺活量（FVC）、用力呼气50%流量（MEF50）、用力呼气25%流量（MEF25）。结 果治疗前各组肺功能男女性比较无统计学差异（均P>0.05）。ICS治疗1年后,正常体质量男女性组FVC%、FEV1%较治疗前 均明显升高（P<0.05）;肥胖男性组FVC%、FEV1%较治疗前明显升高（P<0.05）,而肥胖女性组仅FVC%较治疗前升高（P< 0.05）。结论ICS治疗能够改善哮喘大气道通气功能,性别对哮喘ICS治疗大气道通气功能的改善依赖于体质量指数,表现为 性别对正常体质量哮喘患儿ICS治疗影响作用较小,而女性肥胖哮喘患儿肺功能改善程度明显低于男性肥胖哮喘患儿。     

可溶性和膜结合性CD14在类风湿关节炎患者外周血中的表达及临床意义

目的:探讨类风湿关节炎(RA)患者血清中可溶性CD14(sCD14)的水平及血浆单核细胞膜结合性CD14(mCD14)的表达与RA的关系。方法:收集78例RA患者和50名健康对照者(对照组)的外周血,酶联免疫吸附试验法检测血清中sCD14的表达,同时分离RA患者和对照组外周血单个核细胞,通过流式细胞术检测mCD14的表达水平,分析CD14的表达水平与RA的关系。结果:RA患者血清中的sCD14与mCD14表达水平均明显高于对照组(P<0.01),RA活动期患者sCD14与mCD14表达水平亦均明显高于RA缓解期患者(P<0.01)。结论:sCD14与mCD14在RA外周血中表达水平异常增高,它们可能参与了RA的发病或病情进展。     

被动吸烟对儿童免疫功能及生长发育的影晌

目的　研究被动吸烟对儿童呼吸系统疾病、唾液中硫氰酸盐含量、非特异性免疫功能的影响。方法　选择条件和生源相近的四所日托幼儿园的 1 0 31名 4～ 6岁的儿童做为调查对象 ,采用自制的家庭成员问卷和儿童健康调查表 ,对其家庭成员吸烟情况及儿童健康状况进行了问卷调查 ,测量身高、体重 ,测定唾液中硫氰酸盐含量、唾液免疫球蛋白 (IgA、IgG、IgM)、唾液溶菌酶。结果　 (1 )幼儿被动吸烟量越大 ,唾液中硫氰酸盐含量越高 ,而唾液中溶菌酶含量越低 ,两项指标不同吸烟量各组两两之间均有显著性差异 (P均 <0 0 1 )。被动吸烟量与唾液硫氰酸盐含量呈正相关 ,被动吸烟量与溶菌酶含量呈负相关 ;(2 )幼儿被动吸烟量越大 ,唾液中IgG、IgA、IgM含量越低 ;(3)幼儿被动吸烟量与一年内呼吸系统疾病发病次数呈正相关 (r=0 1 9,P <0 0 1 ) ;(4)被动吸烟影响儿童身高、体重 ,年龄段较大者较年龄段较小者明显。结论　家庭成员吸烟导致儿童被动吸烟可对儿童健康造成危害 ,应动员全社会的力量 ,减少儿童在家庭和公共场所内受吸烟危害     

The Simultaneous Onset of Pancreatitis and Colitis as Immune-related Adverse Events in a Patient Receiving Nivolumab Treatment for Renal Cell Carcinoma

Immune checkpoint inhibitors (ICIs), which have anti-tumor effects, are currently approved for treatment of several kinds of advanced malignancies. However, with their increasing use, a variety of immune-related adverse events (irAEs) in administered patients have been reported. We herein report a rare case of the simultaneous onset of acute pancreatitis and colitis as irAEs during nivolumab treatment given to a patient with renal cell carcinoma, who then shown marked improvement with corticosteroid therapy.     

Effects of Diastolic Blood Pressure on Brain Structures and Cognitive Functions in Middle and Old Ages: Longitudinal Analyses

Hypertension is a pervasive public health concern due to strong associations with cardiovascular diseases and stroke. Alternatively, the associations between hypertension and the risk of Alzheimer’s disease are complex and recent large sample studies reported positive associations. In this paper, we examine the associations between diastolic blood pressure (BP) and subsequent changes in brain structure and cognitive function over several years by multiple regression analyses (with adjustment for a wide range of potential confounding variables) among a large cohort from the UK Biobank. Higher baseline diastolic BP was associated with a slightly smaller relative increase (relative improvements) in reaction time and a slightly greater reduction in depression scores. Higher baseline diastolic BP was also associated with a greater total gray matter volume (GMV) retention, while aging alone was associated with GMV reduction. White matter microstructural analyses revealed that a greater diastolic BP was associated with reduced longitudinal mean and regional fractional anisotropy, greater increases in mean and regional mean diffusivity, radial diffusivity, and axial diffusivity, a greater decline in mean intracellular volume fraction, and greater increases in mean and regional isotropic volume fraction. These white matter microstructural changes were consistent with those seen in the aging process. Additional analyses revealed a greater cheese intake level at baseline, which is associated with a subsequent decline in diastolic BP and a relative subsequent increase in depressive tendency together with a relative increase in fluid intelligence and visuospatial memory performance. These results are congruent with the view that a higher BP in the aging brain has a complex role.     

月见草花浸液对正常小鼠免疫功能的影响

目的:探讨月见草花提取物对正常小鼠免疫功能的影响。方法:ICR小鼠随机分组,给药8天后测定月见草花浸液对小鼠胸腺重量的影响。应用巨噬细胞吞噬功能测定和空斑形成试验,检测月见草花浸液对正常小鼠部分免疫功能的影响。结果:月见草花浸液可明显促进小鼠的腹腔巨噬细胞的吞噬能力,提高小鼠的抗体生成细胞数。结论:月见草花浸液对小鼠的免疫功能具有一定的免疫促进作用。     

Association of Dietary Inflammatory Potential with Blood Inflammation: The Prospective Markers on Mild Cognitive Impairment

Inflammation is known as an important mechanism of cognitive dysfunction. Systemic immune inflammation index (SII) and system inflammation response index (SIRI) are two blood inflammatory markers, which are related to many chronic diseases including cognitive impairment. It is recognized that dietary inflammatory index (DII), which is used to estimate the overall inflammatory potential of diet, may be related to mild cognitive impairment (MCI) as well. This study aimed to explore the relationship between SII, SIRI and DII, as well as the role of these inflammatory indexes on MCI in elderly people. A total of 1050 participants from Beijing were included. Neuropsychological tests were used for cognitive evaluation. Energy-adjusted DII scores were calculated based on semi-quantitative food frequency questionnaire. Blood samples were tested for calculating SII and SIRI. Log-binomial regression models were used to estimate the correlation of indexes. After adjusting demographic characteristics, SII and SIRI in MCI individuals were higher than controls (p ≤ 0.001). DII, SII and SIRI had positive relationship with MoCA scores (p < 0.005). DII also correlated with SIRI in MCI (β = 0.11, p = 0.031). Higher DII and SIRI could definitely increase the risk of MCI, as well as DII and SII (p < 0.005). In conclusion, DII was positively correlated with blood inflammation. The elderly with higher level of DII and SIRI, or DII and SII could be considered as people with higher risk of developing MCI.