Expression of TRIM22 mRNA in chronic hepatitis C patients treated with direct-acting antiviral drugs

Hepatitis C is a global public health problem, and Pakistan is the second largest country in the globe with highest prevalence rate of hepatitis C virus (HCV). Until 2014, pegylated interferon (PEG-IFN) plus ribavirin (RBV) has been the standard therapy for HCV, however, owing to its adverse side effects and very low sustained virologic response (SVR) rates therapeutics trend is shifted toward direct-acting antivirals. Tripartite motif containing 22 (TRIM22) is a dynamic antiviral protein that can inhibit multiple viruses in vivo. Expression of TRIM22 mRNA has been linked to outcome of PEG-IFN and ribavirin therapy, where its higher expression leads to rapid virus clearance. However, in terms of therapy with direct-acting antiviral (DAA) or double DAA, impact of TRIM22 expression is largely unknown. These new drugs show more than 90% of SVR rates and lesser side effects and have proven to be better than IFN therapy. Endogenous IFN system suppresses various pathogens through the induction of antiviral effectors termed as interferon-stimulating genes (ISGs). We have studied the expression levels of one of these antiviral effectors, TRIM22 in response to sofosbuvir (SOF) and daclatasvir (DAC) in combination with RBV, using quantitative PCR in the peripheral blood mononuclear cells (PBMCs) of HCV-infected patients. We have observed sustained virus clearance in more than 90% of patients treated with DAA and double DAA and have seen the expression of TRIM22 to be higher in patients who attained SVR as compared to the untreated patients. We have also observed downregulation of TRIM22 in patients who failed to attain rapid virus clearance, and upregulation in those who achieved rapid clearance of virus. Genetic factors that determine the lower TRIM22 expression in these patients are needed to be explored that may also play a role in lower response to anti-HCV therapy. Endogenous IFN system and effects of antiviral proteins in response to DAA therapy is needed to be studied in order to better understand the host response toward these drugs to make them more effective.     

高危型人乳头瘤病毒感染宫颈病变患者体质特点探析

目的探究高危型人乳头瘤病毒(HR-HPV)感染的宫颈病变患者中医体质分布特点,分析其临床特征与体质类型的关系,为中医药防治HR-HPV感染导致的宫颈病变提供依据。方法采用流行病学研究方法,以问卷调查的方式收集135例HR-HPV感染的宫颈病变患者相关信息,进行体质判定,分析其体质分布特点及主要体质类型与宫颈病变程度、HR-HPV感染特点、年龄及p16抑癌蛋白表达强度的关系。结果HR-HPV感染的宫颈病变患者体质类型所占比例由高到低依次为湿热质、阳虚质、平和质、气虚质、气郁质、阴虚质、痰湿质、血瘀质、特禀质,差异有统计学意义(P<0.05)。不同体质类型患者的宫颈病变程度、HR-HPV感染特点、年龄、p16抑癌蛋白表达强度比较,差异有统计学意义(P<0.05)。结论HR-HPV感染的宫颈病变患者体质类型以湿热质、阳虚质为主,其体质类型与宫颈病变程度、HR-HPV感染特点、年龄、p16抑癌蛋白表达强度有关。     

CIP2A在子宫内膜样腺癌中的表达及临床意义

目的:探究蛋白磷酸酶2A(CIP2A)在子宫内膜样腺癌中的表达情况及临床意义。方法:选取2011年1月至2014年3月行手术切除并经病理证实的50例子宫内膜样腺癌(EAC)及同期行门诊刮宫术获取的40例正常增生期子宫内膜(NE)组织标本。应用RT-PCR、Western blot法检测EAC和NE组织中CIP2A mRNA及蛋白水平，免疫组化法检测CIP2A阳性表达情况。分析CIP2A在EAC和NE组织中的表达差异及与子宫内膜样腺癌临床病理特征的关系。采用Kaplan-Meier法分析CIP2A不同表达水平对患者预后生存的影响，通过COX分析预后独立危险因素。结果:免疫组化染色显示:CIP2A在子宫内膜样腺癌中呈高表达，阳性着色定位于细胞浆和细胞核中，EAC组织中CIP2A阳性表达率显著高于NE组织(P＜0.01)。RT-PCR和Western blot检测显示EAC组织中CIP2A mRNA及蛋白表达水平高于NE组织(P＜0.01)。CIP2A表达与EAC的组织学分级、FIGO分期、宫颈管受累情况、p53表达及Ki-67增殖指数有关（P＜0.05）。Kaplan-Meier法生存分析显示EAC患者5年无病生存率为92.0%、总生存率为88.0%；CIP2A表达、组织学分级、FIGO分期、肌层浸润深度、附件转移、脉管内癌栓及Ki-67增殖指数与患者预后不良相关（P＜0.05）。多因素分析显示，组织学分级、FIGO分期及脉管内癌栓是影响子宫内膜样腺癌患者预后生存的独立危险因素（P＜0.05）。结论:CIP2A在子宫内膜样腺癌中呈高表达，与患者总生存率下降相关，并非影响患者预后的独立危险因素。     

EphB6受体在恶性肿瘤中的研究进展

受体酪氨酸激酶(RTKs)是一种主要的膜受体,调控细胞增殖、分化和迁移。解除RTK信号通路的管制会导致许多疾病,如癌症和发育障碍。促红细胞生成素肝细胞受体(Erythropoietin-producing hepatocellular,Eph)家族是酪氨酸激酶受体家族中最大的一个亚族,其与配体Ephrin的相互作用在生长发育和肿瘤发生过程中发挥着重要作用。研究表明,一种缺乏酪氨酸激酶活性的特殊Eph受体EphB6在乳腺癌、结直肠癌等许多恶性肿瘤中表达下降,而大量证据表明EphB6表达的缺失依赖于其启动子DNA的高甲基化,进而促进肿瘤的进展与转移。EphB6是近期研究的热点因子,本文就其目前在恶性肿瘤中研究进展做一综述。     

抗PD-(L)1、抗CTLA-4免疫治疗标志物研究进展

免疫检查点抑制剂已经改变了包括肺癌、黑色素瘤等许多肿瘤的治疗情况，并且在一些难治性肿瘤中表现出持久的应答率，然而在部分接受治疗的患者中表现出无反应及严重免疫相关副作用。为了优化免疫疗法的使用，可能需要多种临床应答的预测性标志物。本研究回顾了几种潜在有效生物标志物的可用数据，通过免疫组化检测肿瘤细胞和免疫细胞中PD-L1的表达，提示其是一种临床疗效的良好预测标志物;且PD-L1表达阴性者经免疫治疗后仍可获益。PD-L1表达在肿瘤内是动态和异质性的:在原发性灶和转移灶之间或在穿刺标本和大体标本之间表达不一致。肿瘤突变负荷与新抗原的高比率可获得持久获益。外周血标志物也可作为潜在标志物，增加的绝对淋巴细胞计数（ALC）与疾病控制和生存显著相关。在这篇综述中，我们旨在讨论抗PD-（L）1与抗CTLA-4 免疫治疗相关标志物研究现状，为临床运用提供指导，以便能够准确筛选出从这些治疗中获益更多的患者。     

Cytokine-related genes play critical roles in extrafollicular growth of follicular lymphoma cells

Follicular lymphoma (FL) is a germinal center-derived B-cell lymphoma that is known to proliferate in the intrafollicular region. However, lymphoma cells can be identified in the extrafollicular regions, which are related to disease dissemination. We purified the intrafollicular and extrafollicular regions of FL cells by laser microdissection and conducted microarray analysis in order to characterize the gene expression profiles of FL cells from both regions. BCL2 and genes of germinal B-cell markers clearly separated intrafollicular and extrafollicular regions of reactive follicular hyperplasia, suggesting the adequacy of the current analysis. In FL cases, cytokine-related genes were significantly enriched in extrafollicular regions compared with those in the intrafollicular regions. In intrafollicular regions of FL, cell-cycle–related genes were enriched. We found that the FL cells in the extrafollicular region more strongly expressed IL3RA and CXCL12 than those of intrafollicular regions. The cytokines might be also derived from stroma cells in the extrafollicular regions, which may initiate activation and migration of the tumor cells to this region. Our results suggest that FL cell interaction with surrounding stroma cells plays an important role in the pathophysiology of FL and that such interactions should be a good target for therapy.     

Compositional analyses reveal correlations between taxon-level gut bacterial abundance and peripheral T cell marker expression in African infants

ABSTRACT

Although exclusive breastfeeding has been linked to lower rates of postnatal HIV transmission compared to nonexclusive breastfeeding, mechanisms underlying this are unclear. Across a longitudinally sampled cohort of South African infants, we showed that exclusively breastfed (EBF) infants had altered gut bacterial communities when compared to nonexclusively breastfed (NEBF) infants, as well as reduced peripheral CD4 + T cell activation and lowered chemokine and chemokine receptor expression in the oral mucosa. We further demonstrated that the relative abundance of key taxa was correlated with peripheral CD4 + T cell activation. Here, we supplement those findings by using compositional data analyses to identify shifts in the abundance of several Bifidobacteria strains relative to select strains of Escherichia, Bacteroides, and others that are associated with the transition to NEBF. We illustrate that the abundance ratio of these taxa is tightly correlated with feeding modality and is a strong predictor of peripheral T cell activation. More broadly, we discuss our study in the context of novel developments and explore future directions for the field.