Genome-wide gene and serum ferritin interaction in the development of type 2 diabetes in adults aged 40 years or older

Background and aimsElevated serum ferritin is associated with incident Type 2 diabetes (T2D), but the interactions between serum ferritin and genetic factors which may improve understanding underlying mechanism in the development of T2D are still unclear. We determined the gene–ferritin interactions on the development of T2D by genome-wide gene–ferritin interaction analyses.Methods and resultsA total of 3405 participants from two prospective cohorts of community living residents were included, and the median follow-time was 3.99 years. Genome-wide gene–ferritin interactions were analyzed using the joint test with two degrees of freedom and the interaction test with one degree of freedom. There were 18 SNPs selected in the joint test. Finally, four independent variants [rs355140 (LINC00312), rs4075576 (nearby PDGFA), rs1332202 (PTPRD), and rs713157 (nearby LINC00900)] with low pairwise linkage disequilibrium (r2 < 0.2) and located at least 1000 kb from the index SNP showed interactions with serum ferritin level. In the association analyses between serum ferritin levels (tertiles of ferritin and ferritin status) and the incidence of T2D according to genotype, the Incidence Rate Ratios (IRRs) in the highest tertile of ferritin level (vs. the lowest tertile) were greater for participants with heterozygotes of risk alleles of each of the four SNP than IRRs for those with wild type. Compared with the normal group, the elevated ferritin group also had a higher risk of T2D for all genetic variants of risk alleles, particularly its homozygotes.ConclusionSerum ferritin level interacts with genetic variants (rs355140, rs4075576, rs1332202, and rs713157) in the development of T2D.     

惠州地区女性体检人群中 HPV 感染情况调查

目的 筛查广东省惠州地区女性体检人群人乳头瘤病毒 (HPV) 感染情况，分析其型别特征、年龄分布特点及宫颈病 变程度。方法 收集 2016 年 8 月-2017 年 6 月共 702 例广东省惠州地区女性体检人群的宫颈脱落细胞标本，采用 Luminex 200 的流式荧光技术检测 27 种人乳头瘤病毒 (HPV) 的基因型，包括高危型别 (17 种 )：16、18、31、33、35、39、45、51、52、56 、 58、59、66、68、26、53 和 82，低危亚型 (10 种 )：6、11、40、42、43、44、55、61、81 和 83。同时对 HPV 分型阳性的标本行 液基细胞学检测 (TCT)。分析 HPV 流行率、感染型别、年龄分布及宫颈病变程度。结果 702 例女性体检人群中 HPV 感染者人 数为 101 例，感染率为 14.4%。HPV 单一感染型占 82.2%(83 例 /101 例 )，以高危亚型为主 (83.1%，69 例 /83 例 )，前 3 位感染亚 型分别是 52 型 (24.1%，20 例 /83 例 )、16 型 (10.8%，9 例 /83 例 )、58 型 (10.8%，9 例 /83 例 )。多重亚型感染占 17.8%(18 例 /101 例 )。 ≤30岁、31~40岁、41~50岁、>50岁年龄组感染率分别为18.7%、14.4%、14.0%和11.7%，各年龄层感染率无统计学差异(P＞0.05)。 其中 92 例 HPV 分型阳性患者同时进行了 TCT 检测，25% 人群宫颈有炎症细胞或出血，10.9% 人群出现了非典型鳞状细胞不能 排除高级别上皮内病变 (ASC-H) 和低度鳞状上皮内病变 (LSIL)。结论 广东省惠州地区女性体检人群中 HPV 感染主要以 52 型、 16 型、58 型为主，且为单一感染，其中部分 HPV 感染体检人群宫颈已经出现了病变。流式荧光技术可以精确分出 27 种最见的 HPV 亚型，对 HPV 的筛查具有良好的应用前景。     

基于数据分析的NFASC与胃癌预后的关系及相关机制

目的:探讨NFASC在胃癌中的预后意义及相关机制。方法:从人类肿瘤相关基因表达汇编（Gene Expression Omibus，GEO）数据库中下载GSE62254胃癌数据集，分析NFASC表达与胃癌临床病理学参数的相关性及对预后的影响；利用Cox模型分析影响胃癌患者总生存期的因素并建立预后预测列线图模型；采用基因集富集分析(GSEA)方法预测NFASC参与的信号通路。结果: NFASC高表达的胃癌患者总生存时间（overall survival，OS）更短（P<0.05），NFASC表达与患者年龄、T分期及Lauren分型相关（P均<0.05）。NFASC高表达富集了TGF-β信号通路、mTOR信号通路、MAPK信号通路和Wnt信号通路等与肿瘤细胞增殖密切相关的通路（P<0.05，FDR<0.25）。结论: NFASC是胃癌的不良预后因素，其表达可能成为胃癌预后预测生物标志物。     

青黛作用于急性幼粒细胞白血病的可视化“药靶蛋白模型”分析

目的:目前青黛已是治疗急性幼粒细胞白血病(APL)的临床有效药物,但其分子机制与物质基础仍不明确。基于此本研究构建青黛与APL可视化药靶蛋白模型,以探究青黛作用于APL的分子机制。方法:通过GEO数据库检索APL微阵列芯片分析APL差异表达基因,使用TCMSP数据库筛选青黛活性成分,结合PubChem和SwissTargetPrediction匹配活性成分的靶基因并进行富集分析。String用于挖掘并构建APL可视化蛋白互作数据,将其读入Cytoscape,通过Centiscape实现网络拓扑分析。综合APL差异表达基因,通过Sybyl与青黛活性成分构建药靶蛋白模型。结果:筛选出3张APL微阵列芯片,164个差异表达基因,9种青黛活性成分,541个靶基因,这些靶点较多地参与细胞凋亡、药物结合、癌症途径、慢性粒细胞白血病等,这些都在APL中起重要作用。拓扑分析显示ELANE,CTSS为核心基因,将其与青黛9种活性成分进行药靶蛋白模型预测,显示靛玉红和靛蓝与核心基因结合度最佳。结论:APL是受多基因调控的复杂疾病,而青黛成分中靛玉红和靛蓝可通过结合ELANE,CTSS作用于APL的发生发展。     

Evaluation of <i>MGMT</i> Gene Methylation in Neuroendocrine Neoplasms

Unresectable neuroendocrine neoplasms (NENs) often poorly respond to standard therapeutic approaches. Alkylating agents, in particular temozolomide, commonly used to treat high-grade brain tumors including glioblastomas, have recently been tested in advanced or metastatic NENs, where they showed promising response rates. In glioblastomas, prediction of response to temozolomide is based on the assessment of the methylation status of the MGMT gene, as its product, O6 -methylguanine-DNA methyltransferase, may counteract the damaging effects of the alkylating agent. However, in NENs, such a biomarker has not been validated yet. Thus, we have investigated MGMT methylation in 42 NENs of different grades and from various sites of origin by two different approaches: in contrast to methylation-specific PCR (MSP), which is commonly used in glioblastoma management, amplicon bisulfite sequencing (ABS) is based on high-resolution, next-generation sequencing and interrogates several additional CpG sites compared to those covered by MSP. Overall, we found MGMT methylation in 74% (31/42) of the NENs investigated. A higher methylation degree was observed in welldifferentiated tumors and in tumors originating in the gastrointestinal tract. Comparing MSP and ABS results, we demonstrate that the region analyzed by the MSP test is sufficiently informative of the MGMT methylation status in NENs, suggesting that this predictive parameter could routinely be interrogated also in NENs.     

IGF2基因在乳腺癌中的研究进展

乳腺癌目前是中国女性发病率第一位的恶性肿瘤， 严重威胁着患者的健康。与乳腺癌相关基因和治疗靶点的研究一直是业界热潮。胰岛素样生长因子2(insulin-like growth factor 2，IGF2)与多种恶性肿瘤的发生与发展存在相关性。随着精准医疗的发展，乳腺癌的治疗越来越趋于个体化，IGF2基因与乳腺癌的侵袭性、发生风险、进展速度、预后治疗是否存在着联系与相关性，笔者总结了IGF2基因在乳腺癌研究的重要成果，包括IGF2基因结构与功能、IGF2基因克隆与表达及IGF2基因与乳腺癌的关系等。     

circCDYL Acts as a Tumor Suppressor in Triple Negative Breast Cancer by Sponging miR-190a-3p and Upregulating TP53INP1

BackgroundBreast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among females. Circular RNAs (circRNAs) have been implicated in the initiation and development of cancer. Here, we explored the biological role and regulatory mechanism of circCDYL in breast cancer.Materials and MethodsThe expression and correlation of circCDYL/miR-190a-3p/TP53INP1 axis in breast cancer tissues and cells were determined by quantitative polymerase chain reaction and Western blot. Cell-counting Kit-8, colony formation, cell migration, and invasion assays were applied to investigate the biological roles of circCDYL in breast cancer development and progression.ResultsCircCDYL were down-regulated in breast cancer tissues and cells, the expression of which positively correlated with patients’ survival rate. CircCDYL worked as a “sponge,” binding to miR-190a-3p directly, which inhibited the expression of miR-190a-3p and relieved the inhibition of tumor suppressor gene TP53INP1.ConclusionCircCDYL promotes apoptosis and inhibits proliferation of the malignant phenotype of breast cancer through regulating miR-190a-3p/TP53INP1 axis, which suggests that circCDYL is a potential therapeutic target for breast cancer.     

症状前期进行性肌营养不良患儿24例病例系列报告

背景：进行性肌营养不良（PMD）中Duchenne型肌营养不良(DMD)和Becker型肌营养不良(BMD)的临床表现、治疗和预后差异明显，目前国内外对症状前期PMD患儿的诊断尚无共识。 目的：探讨婴幼儿时期症状前期PMD患儿的临床特征和实验室检查特点，并探讨血清肌酶水平在DMD和BMD分型诊断中的价值。 设计：病例系列报告。 方法：收集2016年1月至2020年7月江西省儿童医院确诊的症状前期PMD患儿，分析临床特征和实验室检查特点，并以基因检测结果为诊断标准分为DMD组和BMD组，血清肌酶通过ROC曲线分析以约登指数最大值时的取值作为诊断界值，比较不同肌酶的诊断准确性。 主要结局指标：PMD患儿的临床表现、基因结果、血清酶水平（AST、ALT、LTH、CK、CK-MB）。 结果：24例PMD患儿纳入分析，其中DMD组18例，BMD组6例。22例（91.7%）因发现转氨酶升高就诊，2例（8.3%）因亲戚确诊前来就医。PMD患儿CK-MB、CK、LDH、AST和ALT水平均明显升高，DMD组均高于BMD组（除AST外，P均<0.05）。当ALT>224.5 U·L-1、CK>11 069 IU·L-1、CK-Mb>204 IU·L-1、LDH>1 349.5 IU·L-1时为DMD的可能性更高，尤其是LDH>1 349.5 IU·L-1具有高度特异性。 结论：血清肌酶水平增高为 PMD 患儿症状前期的主要表现。LDH＞1 349.5 IU·L-1对诊断DMD具有高度特异性。     

DNA methylation signatures reveal that distinct combinations of transcription factors specify human immune cell epigenetic identity

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PTGS1基因多态性与急性脑梗死患者阿司匹林抗血栓疗效的相关性

目的 探讨前列腺素内过氧化物合酶1(Prostaglandin-endoperoxide synthase1, PTGS1)基因多态性与急性脑梗死患者阿司匹林抗血栓疗效的相关性。方法 回顾性分析2017年10月-2020年10月在本院接受治疗的200例急性脑梗死患者的临床资料,按照其阿司匹林抗血栓疗效将其分为阿司匹林抵抗组(n=69)和阿司匹林敏感组(n=131),分析所有患者PTGS1基因多态性情况,比较2组性别、年龄、身体质量指数(Body Mass Index,BMI)、合并症(高血压病、冠心病、糖尿病)、PTGS1基因突变、不良嗜好(吸烟、酗酒)等临床特征及生化指标[血小板计数(Blood platelet,PLT)、超敏C反应蛋白(Hypersensitive-C reactive protein,hs-CRP)]水平,利用受试者工作特征(Receiver operating characteristic,ROC)曲线分析PLT,hs-CRP预测急性脑梗死患者阿司匹林抵抗的价值,将2组有差异的指标纳入Logistic回归分析模型,进行量化赋值,明确引起急性脑梗死患者阿司匹林抵抗的危险因素。结果 本研究200例急性脑梗死患者中PTGS1基因位点以AA为主,发生率为81.50%,其突变基因位点分别为AG,GG,占人数的14.00%、4.50%。阿司匹林抵抗组年龄≥60岁、合并糖尿病、PTGS1基因突变、吸烟患者的比例及PLT,hs-CRP水平显著高于阿司匹林敏感组(P<0.05)。经ROC曲线分析PLT,hs-CRP预测急性脑梗死患者阿司匹林抵抗的曲线下面积分别为0.879、0.866。年龄≥60岁、合并糖尿病、PTGS1基因突变、吸烟、PLT≥202.255×10⁹/L,hs-CRP≥24.695 mg/L是引起急性脑梗死患者阿司匹林抵抗的危险因素。结论 PTGS1基因多态性会增加急性脑梗死患者阿司匹林抵抗风险。除此之外,高龄、糖尿病、抽烟及PLT,hs-CRP异常高表达均可能影响阿司匹林抗血栓治疗效果。