子宫内膜异位症血清标志物研究进展

子宫内膜异位症是一种常见的妇科良性疾病。目前,临床对子宫内膜异位症虽然有比较有效的治疗方案,但尚缺乏有效的早期的诊断标志物。腹腔镜是子宫内膜异位症的金标准诊断方法,但需要对患者进行全身麻醉,且手术并发症及诊断费用较高。因此,迫切需要一种简单、微创、准确和快捷的对子宫内膜异位症的诊断方法[1]。本文通过对目前较为常用的血清标志物、血清miRNA、血清甲基化、血清细胞因子等几个方面对子宫内膜异位症的血清标志物进行综述。     

子宫内膜异位症实验室诊断研究进展

子宫内膜异位症（EMs）病因复杂，其诊断亦较困难，腹腔镜检查是目前诊断EMs的“金标准”，但是腹腔镜检查适应症有限，且步骤繁琐，因此寻找有效的血清和（或）腹水诊断标志物对筛查和诊断EMs具有十分重要的意义。目前在肿瘤标志物、免疫学标志物方面已进行了广泛研究，具有诊断价值的标志物包括CA125、sICAM-1、TNF-α、IL-6、EMAb、抗转铁蛋白抗体等，不过各种标志物诊断价值均有局限，近年来研究深入到基因多态性等遗传学标志物领域，已发现一些与EMs密切相关的基因。本文就近年来EMs实验室诊断的研究进展作一综述。     

子宫内膜异位症的超声诊断

目的探讨子宫内膜异位症的超声诊断价值。方法收集2012年1月~2013年12月在我院经过腹腔镜手术确诊患有子宫内膜异位症的93名患者超声影像特征,对比分析内在性子宫内膜异位症与外在性子宫内膜异位症的影响特征差异;结果 1子宫内膜异位症超声征象主要表现为:包块外形包块规则(占63%)、包块边界不清晰(占77.2%)、包块回声为无回声(占68.5%)或低回声(占27.2%)、内部无回声(占72.8%);无血流信号(占80.4%);2内在性子宫内膜异位症患者具有妊娠分娩史的占86.1%高于外在性子宫内膜异位症的66.1%;包块边界不清晰率88.9%高于外在性组的69.6%,组间差异显著;3超声诊断准确率达91.4%;结论超声对子宫内膜异位症的诊断便捷、准确率高、费用合理,但尚存在不符合特异征象的影像表现,需同时结合临床病史及其他指标进行联合诊断。     

不同部位子宫内膜异位症的超声诊断分析

目的 探讨不同部位的子宫内膜异位症(endometriosis,EM)的声像图特征及超声诊断价值.方法 回顾分析229例不同部位EM的超声检查资料.结果 内在性EM即子宫腺肌症78例,以灶性斑点状稍高回声为特点;外在性EM151例,其中盆腔巧克力囊肿142例,呈囊性,囊内回声复杂多样;腹壁疤痕EM5例,膀胱壁EM 1例,会阴侧切口EM1例,宫颈EM 1例,肠壁EM 1例,均表现为不均匀低回声肿块.结论 EM发病是广泛性的和多样的,不同部位EM的声像图特征不同;超声检查简单、快捷、价廉、无创伤,是目前诊查EM有效的首选检查方法.     

抗子宫内膜抗体在子宫内膜异位症诊断中的评价

本文采用纯化了的人子宫内膜抗原以间接酶联免疫法检测经手术或腹腔镜证实了的子宫内膜异位症患者62例，单纯子宫肌腺病者8例及正常对照组30例的血标本，结果发现子宫内膜异位症组抗宫内膜抗体阳性率为58．6%，子宫内膜异位症之不育患者抗宫内膜抗体阳性率为72．22%，均明显高于对照组6．67%及子宫肌腺病组12．5%，并且发现子宫内膜异位症组中抗内膜抗体的阳性率随其分期的升高而下降，Ⅳ期子宫内膜异位症之阳性率已与对照组无差异。认为：抗子宫内膜抗体的检测不失为一种对子宫内膜异位症患者无捐伤的，经济方便的辅助诊断方法，尤其对轻度子宫内膜异位症患者更具价值。     

子宫内膜异位症对子宫内膜容受性的影响

子宫内膜异位症（Endometriosis,EMs）是妇科常见病,也是女性不孕的常见原因之一,它通过影响生殖过程的各个环节而导致不孕.其中对胚胎植入的影响包括子宫内膜超微结构的改变、细胞因子及黏附分子的表达紊乱、同源盒基因HOXA10的下调等所致的子宫内膜容受性的下降.     

血清CA125水平与子宫内膜异位症关系的Meta分析

目的 系统评价血清CA125水平与子宫内膜异位症的关系.方法 计算机检索PubMed、Embase、WanFang、CNKI等数据库关于血清CA125水平与子宫内膜异位症关系的病例对照研究,搜索诸数据库自建库至2017年6月.按照纳入与排除标准筛选文献,应用Stata12.0软件进行Meta分析.结果 共纳入8个研究,1061例样本,其中观察组655例,对照组406例.剔除异质性较大的研究后Meta分析结果显示:与对照组比较,观察组的血清CA125水平[SMD=1.60,95% CI (1.27~1.92)]明显增高,差异有统计学意义(Z=9.69,P<0.005).结论 血清CA125水平与子宫内膜异位症关系密切,可作为临床评价的依据.     

子宫内膜异位症患者的皮纹学分析

本文对５４例子宫内膜异位症患者进行皮纹学分析，与文献国内女性正常值比较有明显差异的是：食指Ａ频率高（１８．５２％，正常３．５％）；尺箕Ｌ＂出现率低（４２．５７±１３．８５，正常４７．４８±０．６９）；各指嵴线数ＦＲＣ低（１２．１２±５．０２，正常１３．８５±５．４３）：总嵴线数ＴＦＲＣ低（１２１．８５±３７．２１，正常１３８．４６±４１．５９）；∠ａｔｄ增加（４２．２７°±４．９３，正常３９．９２°±６．６０）。     

血清CA125IRMA诊断子宫内膜异位症的价值

子宫内膜异位症(EM)是育龄妇女的多发病,目前它的诊断主要依赖临床症状、妇科检查、B超和腹腔镜技术.近年开始应用抗子宫内膜抗体(EmAb)和CA125的血清学检测作为辅助方法,但对它们的诊断价值评价不一[1-3].本文通过检测55例EM患者血清据以探讨GA125对EM的诊断价值. 资料和方法     

LNG-IUS治疗子宫内膜增生的预测性生物标志物

子宫内膜增生是一种常见的疾病,是由于外源性或内源性雌激素增多或孕激素的缺乏导致的子宫内膜组织的异常、非侵袭性增生。为了抑制其进展为子宫内膜癌,临床医生对子宫内膜增生保持高度警惕。现阶段治疗子宫内膜增生的方法有手术治疗和保守治疗两种,保守治疗分为全身孕激素治疗和左炔诺孕酮宫内缓释系统（LNG-IUS）。文中作者将对左炔诺孕酮宫内缓释系统治疗子宫内膜增生的疗效及优点进行论述,并对目前研究中可预测LNG-IUS治疗子宫内膜增生疗效的潜在生物标志物作一综述。     

Anti-p53 autoantibody in blood as a diagnostic biomarker for colorectal cancer: A meta-analysis

Serum autoantibodies against tumour-associated antigens are promising biomarkers for diagnosis of cancer. This review summarizes the available evidence pertaining to the diagnostic potential of autoantibodies studied in the context of colorectal cancer (CRC). A systematic literature search was conducted in three databases (PubMed, Cochrane Library and Embase). Data pertaining to a total of 145 autoantibodies published in 80 articles were reviewed. Of these, anti-p53 antibody was the most commonly studied autoantibody; thus, we performed a meta-analysis on anti-p53 antibody in 24 articles. According to the cut-off values used to determine positivity for anti-p53 antibody, we divided the included studies into five groups. Owing to the presence of threshold effect in groups 4 and 5 and non-threshold effect in groups 1 and 2, pooled analysis focused on group 3 using a fixed-effects model (Mantel-Haenszel). Group 3, determining the cut-off value based on the value of p53 antibody titre index, was comprised of five articles including 733 patients with CRC and 172 controls (126 healthy individuals and 46 benign diseases). The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and summary area under the receiver operating characteristic curves were 0.21, 0.99, 12.26, 0.80, 15.46 and 0.87, respectively. Serum anti-p53 autoantibody may potentially help distinguish CRC from healthy controls or benign diseases; however, it should be used in combination with other indicators due to the low sensitivity. Our study provides insights for further exploration of the optimal combination of different tumour-associated antigens or autoantibodies for diagnosis of CRC.     

Aberrant DNA methylation as a diagnostic biomarker of diabetic embryopathy

PurposeMaternal diabetes is a known teratogen that can cause a wide spectrum of birth defects, collectively referred to as diabetic embryopathy (DE). However, the pathogenic mechanisms underlying DE remain uncertain and there are no definitive tests to establish the diagnosis. Here, we explore the potential of DNA methylation as a diagnostic biomarker for DE and to inform disease pathogenesis.MethodsBisulfite sequencing was used to identify gene regions with differential methylation between DE neonates and healthy infants born with or without prenatal exposure to maternal diabetes, and to investigate the role of allele-specific methylation at implicated sites.ResultsWe identified a methylation signature consisting of 237 differentially methylated loci that distinguished infants with DE from control infants. These loci were found proximal to genes associated with Mendelian syndromes that overlap the DE phenotype (e.g., CACNA1C, TRIO, ANKRD11) or genes known to influence embryonic development (e.g., BRAX1, RASA3). Further, we identified allele-specific methylation (ASM) at 11 of these loci, within which 61.5% of ASM single-nucleotide variants are known expression quantitative trait loci (eQTLs).ConclusionsOur study suggests a role for aberrant DNA methylation and cis-sequence variation in the pathogenesis of DE and highlights the diagnostic potential of DNA methylation for teratogenic birth defects.     

Potential of RASSF1A promoter methylation as a biomarker for colorectal cancer: Meta-analysis and TCGA analysis

The RAS association domain family protein 1A (RASSF1A) is a tumor suppressor in colorectal cancer (CRC), and is often inactived by hypermethylation. Therefore, we evaluated the association between RASSF1A hypermethylation and the risk and prognosis in CRC. We identified literature through searching PubMed and China National Knowledge Infrastructure databases, and then validated and supplemented the meta-analysis with TCGA analysis. Twenty-three studies involving 2886 subjects of CRC were examined. The meta-analysis showed that RASSF1A promoter methylation inferred high CRC risk (odds ratio, 6.53, 95% confidence interval 3.88–11.01, P < .001) and poor overall survival (hazard ratio 2.85, 95% CI 1.88–4.31, P < .001). The TCGA analysis suggested that effect of RASSF1A promotor methylation was affected by tumor localization (colon vs. rectum). RASSF1A promoter methylation was a predictor of high risk (OR 2.38, 95%CI 1.02–5.6, P = .046) and poor disease free survival(HR 2.25, 95%CI 1.27–3.99, P = .006)in colon adenocarcinoma, but the association was statistically insignificant in rectum adenocarcinoma(HR 1.58, 95% CI 0.69–3.59, P = .28). These results suggested RASSF1A hypermethylation is a risk and a potential prognostic biomarker in CRC.     

外周血甲基化Septin-9-检测对结直肠癌诊断价值的Meta分析

目的:Meta 系统性评价Septin-9 在结直肠癌中的诊断价值。方法:检索PubMed、生物医学外文全文服务系统、Ovid、中国学术期刊全文数据库、中国生物医学文献数据库、维普中文科技期刊数据库、万方数据库,日期截止至2017 年1月。严格按照纳入和排除标准筛选文献,并依据QUADAS 标准对文献进行质量评估。使用双变量Meta 模型合并检验效能分析,通过Q 检验、I2 检验检测研究异质性,通过亚组分析、敏感性分析探讨异质性来源,通过Deek's 漏斗图评估发表偏移。结果:共纳入11 篇文献;Septin-9 诊断结直肠癌的合并敏感度为0.70(95%CI:0.67 ~0.72),合并特异度为0.91(95% CI:0.90 ~0.92),诊断比值比为28.76(95%CI:17.70 ~46.75),SROC 的曲线下面积(AUC)为0.922 1。异质性检验提示不存在阈值效应,但存在其他因素引起的异质性。通过敏感性分析发现纳入文献中有一个离群值。亚组分析结果显示,根据1/3 判为阳性和2/3 判为阳性分组:AUC 为0.939 7 比0.826 5。根据亚洲人种和欧美人种分组:AUC 为0.936 8 比0.921 0。Deek's 漏斗图评估纳入文献不存在发表偏倚。结论:外周血甲基化Septin-9 诊断结直肠癌的整体准确性较高,可作为一项很好的指标用于结直肠癌诊断。     

Circular RNAs as diagnostic biomarker in pancreatic cancer

Pancreatic cancer is one of the causes of death in the world. Unfortunately, common imaging technologies did not succeed in identifying this disease, and because of the absence of sensitive and specific biomarkers, it is not possible to screen and diagnose the disease. Therefore, this disease is usually diagnosed when patient is at an advanced stage of cancer and has lost the chance of surgery, and routine treatments such as radiotherapy and chemotherapy are not very effective. For this reason, the discovery of new biomarkers to overcome the diagnostic and therapeutic problems of pancreatic cancer is essential. Recently, circular RNAs (circRNAs) have been introduced as a group of noncoding RNAs that can play the role of critical regulators in various human diseases including cancer. A lot of studies revealed that circRNAs can have diverse roles in various cancers, including breast, colorectal, lung, renal, gastric, and hepatocellular carcinoma. The results of these researches have demonstrated that change in circRNAs expression levels in the tumor cells affects carcinogenesis, the stages of progression and metastasis of cancer through various mechanisms. Given that several studies have tested the role of circRNAs in pancreatic cancer, we decided to review the mechanisms proposed in these studies to conclude and summarize the work done in this regard.     

A genome-wide expression analysis in blood identifies pre-elafin as a biomarker in ARDS

Previous microarray-based studies of acute respiratory distress syndrome (ARDS) were performed using various models to mimic disease pathogenesis. The complexity of the pathophysiologic response to direct or indirect lung injury in ARDS is difficult to reconstruct in experimental conditions. Thus, direct analysis of ARDS patient blood may provide valuable information. We investigated genome-wide gene expression profiles in paired whole blood samples from patients with ARDS (n = 8) during the acute stage (within 3 d of diagnosis) and recovery stage of ARDS (around ICU discharge). Among 126 differentially expressed genes, peptidase inhibitor 3 (PI3, encoding elafin, a potent neutrophil elastase inhibitor) had the largest fold-change (-3-fold changes, acute stage/recovery stage) in expression, indicating down-regulation during the acute stage of ARDS. We further examined plasma PI3 levels in 40 patients with ARDS and 23 at-risk control subjects from the same cohort. There was a coincidence of the microarray findings of lower PI3 gene expression with the lower plasma PI3 during the acute-stage. The plasma PI3 levels were statistically significant different among pre-diagnosis, day of diagnosis, and post-diagnosis groups (ANOVA, P = 0.001), with a trend of decreasing from pre- to post-diagnosis group. The time course of plasma PI3 decrease is well correlated with the course of early ARDS development (Pearson correlation coefficient: -0.52, P = 0.0006). Considering that PI3 can covalently binding to extracellular matrix in lung, circulating PI3 may provide a useful clinical marker for monitoring the early development of ARDS and may have implications for ARDS treatment.     

Detection of cord blood hepcidin levels as a biomarker for early-onset neonatal sepsis

Early-onset neonatal sepsis (EONS) continues to be a severe condition associated with a high mortality and morbidity. However, symptoms and laboratory markers of this serious condition are nonspecific and currently there are no available standard tests to provide perfect diagnostic accuracy. An early recognition and initiation of antimicrobial therapy are essential in order to prevent morbidity and mortality. Hepcidin, the key regulator of iron homeostasis, is also an acute-phase reactant, which has a critical role in inflammation and contributes to host defense by interfering with microorganism’s access to iron. Since hepcidin expression is induced by interleukin-6 (IL-6), it also plays role in the innate immune system. Recently, endogenous expression of hepcidin by macrophages and neutrophils in response to bacterial pathogens confirmed its role in innate immunity. The clear link between the hepcidin molecule and innate immunity may be used for the detection of EONS. We hypothesized that an increased level of hepcidin in cord blood may be used as a reliable biological marker of EONS and designed a prospective cohort study to test this hypothesis and collected pilot data. Cord blood samples of all infants born between January 2009 and December 2010 at our university hospital were collected after parental consent and a total of 38 infants were enrolled in the study who fulfilled the sepsis criteria. The range of cord blood hepcidin was found to be significantly increased in newborns with EONS (min–max: 118.1–8400 ng/mL). To the best of our knowledge, this is the first study to investigate the pathophysiologic relevance of hepcidin in EONS and demonstrate increased levels of hepcidin in cord blood as an acute-phase reactant in response to sepsis.