医疗机构放射工作人员血清中胰岛素样生长因子结合蛋白3水平的影响因素分析

目的 探究低剂量电离辐射对医疗机构放射工作人员外周静脉血清中胰岛素样生长因子结合蛋白3（IGFBP-3）表达水平的影响。方法 采用单纯随机抽样法选取183名放射工作人员纳入此次研究,按放射工种分组,其中介入放射学组37例、核医学组43例、放射治疗组48例和诊断放射学组55例。血清IGFBP-3浓度测定采用酶联免疫吸附试验。结果 4个不同工种组间放射工作人员血清IGFBP-3浓度的差异具有统计学意义（F＝6.056,P<0.05）,其中介入放射学组血清IGFBP-3浓度最高（t＝2.815、3.611、3.936,P<0.05）;不同年有效剂量组间放射工作人员血清中IGFBP-3的浓度差异具有统计学意义（F＝8.380,P<0.05）。随着放射工龄和年有效剂量的增加,放射工作人员血清IGFBP-3浓度呈现上升趋势（r_s=0.202、0.151,P<0.05）。结论 血清IGFBP-3表达水平有作为反映长期慢性低剂量电离辐射累积暴露的生物标志物的潜力。     

Plasma neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in adult critically ill patients: A prospective study

Purpose

The aim of the study was to assess the ability of plasma neutrophil gelatinase-associated lipocalin (pNGAL) to predict acute kidney injury (AKI) in adult intensive care unit (ICU) patients.

Methods

All consecutives patients admitted to 3 ICUs were enrolled in this prospective-observational study. Plasma neutrophil gelatinase-associated lipocalin was analyzed at ICU admission. Risk, injury, failure, loss, and end-stage kidney (RIFLE) criteria were calculated at admission and for each day during the first week. Patients were classified according to whether they met the threshold for RIFLE criteria (RIFLE 0 or 1) at admission and during the first week. Four groups were identified: RIFLE (0-0), (1-1), (1-0), and (0-1).

Results

During this 1-month period, 88 patients were included in the study. Thirty-six patients met the criteria for RIFLE 0-0 with a mean pNGAL of 98 ± 60 nmol/L, 22 for RIFLE 1-1 with a mean pNGAL of 516 ± 221 nmol/L, and 20 patients had no AKI at admission but develop AKI at 48 hours (24-96 hours) (RIFLE 0-1) with a pNGAL of 342 ± 183 nmol/L. Ten patients met the criteria for RIFLE 1-0 and had a mean pNGAL of 169 ± 100 nmol/L. Using a cutoff of 155 nmol/L, sensitivity and specificity to predict AKI were 82% and 97%, respectively (area under the curve [AUC] = 0.92 [0.852-0.972]; P = .001). Looking at the patients without AKI at admission (n = 56) and who developed (n = 20) or did not develop (n = 36) AKI, receiver operating characteristic curve analysis was as follows: AUC = 0.956 (0.864-0.992). Sensitivity was 85% and specificity was 97%. Of the 7 patients who required renal replacement therapy, all of them had pNGAL of more than 303 nmol/L (AUC = 0.788 [0.687-0.868]).

Conclusion

Plasma neutrophil gelatinase-associated lipocalin at ICU admission is an early biomarker of AKI in adult ICU patients. Plasma neutrophil gelatinase-associated lipocalin increased 48 hours before RIFLE criteria.     

Bile acid indices as biomarkers for liver diseases I: Diagnostic markers

BACKGROUNDHepatobiliary diseases result in the accumulation of toxic bile acids (BA) in the liver, blood, and other tissues which may contribute to an unfavorable prognosis.AIMTo discover and validate diagnostic biomarkers of cholestatic liver diseases based on the urinary BA profile.METHODSWe analyzed urine samples by liquid chromatography-tandem mass spectrometry and compared the urinary BA profile between 300 patients with hepatobiliary diseases vs 103 healthy controls by statistical analysis. The BA profile was characterized using BA indices, which quantifies the composition, metabolism, hydrophilicity, and toxicity of the BA profile. BA indices have much lower inter- and intra-individual variability compared to absolute concentrations of BA. In addition, BA indices demonstrate high area under the receiver operating characteristic curves, and changes of BA indices are associated with the risk of having a liver disease, which demonstrates their use as diagnostic biomarkers for cholestatic liver diseases.RESULTSTotal and individual BA concentrations were higher in all patients. The percentage of secondary BA (lithocholic acid and deoxycholic acid) was significantly lower, while the percentage of primary BA (chenodeoxycholic acid, cholic acid, and hyocholic acid) was markedly higher in patients compared to controls. In addition, the percentage of taurine-amidation was higher in patients than controls. The increase in the non-12α-OH BA was more profound than 12α-OH BA (cholic acid and deoxycholic acid) causing a decrease in the 12α-OH/ non-12α-OH ratio in patients. This trend was stronger in patients with more advanced liver diseases as reflected by the model for end-stage liver disease score and the presence of hepatic decompensation. The percentage of sulfation was also higher in patients with more severe forms of liver diseases.CONCLUSIONBA indices have much lower inter- and intra-individual variability compared to absolute BA concentrations and changes of BA indices are associated with the risk of developing liver diseases.     

Differential expression of HER2 and downstream proteins in prediction of advanced tumor phenotypes and overall survival of patients with Epstein-Barr virus-positive vs. negative gastric cancers

This study evaluated the associations of HER2 protein, HER2 gene amplification, and positivity for p-AKT, p-ERK, and p-PLCγ proteins with clinicopathological status and overall survival (OS) of patients who had Epstein-Barr virus-associated gastric cancer (EBVaGC; n = 58) or EBV-negative GC (EBVnGC; n = 329). Tissue samples were subjected to immunohistochemistry and fluorescence in situ hybridization (FISH). Results showed that EBVaGC less expressed HER2 and amplified HER2 gene. p-AKT (p = 0.035) and p-ERK (p = 0.001) were inhibited in EBVaGC than in EBVnGC, while p-PLCγ (p = 0.034) was upregulated. Among EBVaGC patients, p-ERK positivity was associated with Lauren classification (p = 0.023), and p-PLCγ positivity was inversely associated with TNM stage (p = 0.041) and lymph node metastasis (p = 0.041). In contrast, among EBVnGC patients, HER2 expression was associated with distant metastasis (p = 0.043) and p-AKT positivity was associated with intestinal subtype (p < 0.004), lymph node metastasis (p = 0.031), distant metastasis (p < 0.001), and elder age (>60y, p < 0.004). Overall analysis showed that EBVaGC patients presented better OS than EBVnGC patients (p = 0.044). Among EBVaGC patients, p-AKT positivity (p = 0.008) was associated with worse OS; as well as, HER2 high expression (p < 0.001), p-AKT positivity (p = 0.010), and p-PLCγ (p < 0.001) were associated with worse OS in EBVnGC patients. Multivariate analysis showed that distant metastasis (95% CI: 1.559 to 4.028, p < 0.001), HER2 high expression (95% CI: 1.058 to 2.454, p = 0.026), and p-PLCγ positivity (95% CI: 1.056 to 2.435, p = 0.027) were independent prognostic predictors of OS in EBVnGC patients. Our results indicated that p-AKT positive patients presented worse OS than p-AKT negative ones in EBVaGC, as well as, HER2, p-AKT, and p-PLCγ are prognostic biomarkers for OS in EBVnGC patients.     

Autoantibodies against MMP-7 as a novel diagnostic biomarker in esophageal squamous cell carcinoma

AIM: To evaluate the diagnostic values of serum autoantibodies against matrix metalloproteinase-7 (MMP-7) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: The MMP-7 cDNA was cloned from ESCC tissues, and MMP-7 was expressed and purified from a prokaryotic system. MMP-7 autoantibodies were then measured in sera from 50 patients with primary ESCC and 58 risk-matched controls, using a reverse capture enzyme-linked immunosorbent assay (ELISA) in which autoantibodies to MMP-7 bound to the pur...     

Pancreatic cancer circulating tumor cells: applications for personalized oncology

Introduction: Pancreatic cancer (PC) is a highly lethal disease, in part because of early metastasis, late diagnosis, and limited treatment options. Circulating tumor cells (CTCs) are cancer cells that have achieved the metastatic step of intravasation, and are thus a unique source of biomarkers with potential applications in the staging, prognostication, and treatment of PC.

Areas covered: This review describes the use of CTCs in PC, including isolation methods, the significance of CTC enumeration, and studies examining phenotypic and molecular characteristics of CTCs. We also speculate on future directions for PC CTC research such as single-cell analysis and CTC culture.

Expert commentary: CTCs represent a potential unique serial source of cancer tissue via a convenient and minimally invasive blood draw. Recent development of isolation methods that allow for the release of viable CTCs with unaltered molecular characteristics has set the stage for single-cell analysis and ex vivo culture. Although there is significant potential for CTCs as a biomarker to impact PC from diagnosis to therapy, there still remain a number of challenges to the routine implementation of CTCs in the clinical management of PC.     

Salivary alkaline phosphatase activity and chronological age as indicators for skeletal maturity

Objectives:To investigate the relationship between salivary alkaline phosphatase activity (ALP), protein concentration, and chronological age with cervical vertebral maturation stages (CVMS) as noninvasive biomarkers for skeletal maturity assessment.Materials and Methods:This cross-sectional study included 79 subjects (48 females, 31 males; 7 to 23 years old) categorized into five CVMS based on lateral cephalographs evaluated by three examiners. ALP activity and protein concentration in unstimulated whole saliva were compared among five CVMS. The association between age and CVMS was assessed and five multinomial logistic regression models were utilized to predict CVMS based on salivary ALP activity, protein concentration, and chronological age.Results:Salivary ALP reached the peak at early pubertal stage and then declined with a significant difference between CVMS I and CVMS II (P < .001) and between CVMS I and CVMS V (P = .004). A significant positive correlation between age and CVMS was found (r_s = 0.763, P < .001). The models'' overall correct classification rates for predicting CVMS were 32.9% using protein concentration, 35.4% using ALP activity, and 53.2% using both ALP activity and age.Conclusions:The combination of salivary ALP activity and chronological age may provide the best CVMS prediction.     

MicroRNAs as potential biomarkers for gastric cancer

Gastric cancer is the fourth most common cancer in the world and the second leading cause of cancerrelated death.More than 80%of diagnoses occur at the middle to late stage of the disease,highlighting an urgent need for novel biomarkers detectable at earlier stages.Recently,aberrantly expressed microRNAs(miRNAs)have received a great deal of attention as potential sensitive and accurate biomarkers for cancer diagnosis and prognosis.This review summarizes the current knowledge about potential miRNA biomarkers for gastric cancer that have been reported in the publicly available literature between 2008 and 2013.Available evidence indicates that aberrantly expressed miRNAs in gastric cancer correlate with tumorigenesis,tumor proliferation,distant metastasis and invasion.Furthermore,tissue and cancer types can be classified using miRNA expression profiles and next-generation sequencing.As miRNAs in plasma/serum are well protected from RNases,they remain stable under harsh conditions.Thus,potential functions of these circulating miRNAs can be deduced and may implicate their diagnostic value in cancer detection.Circulating miRNAs,as well as tissue miRNAs,may allow for the detection of gastric cancer at an early stage,prediction of prognosis,and monitoring of recurrence and/or lymph node metastasis.Taken together,the data suggest that the participation of miRNAs in biomarker development will enhance the sensitivity and specificity of diagnostic and prognostic tests for gastric cancer.     

sLOX-1：一个极具研究潜力的心血管疾病诊断生物标志物

凝集素样氧化型低密度脂蛋白受体1(LOX-1)是血管内皮细胞上氧化型低密度脂蛋白的主要受体,其胞外结构域被降解后释放到血液中,形成可溶性LOX-1(s LOX-1)。血清s LOX-1水平在动脉硬化及血管内皮细胞损伤相关疾病患者中明显升高,是极具研究潜力的生物标志物。本文首次对s LOX-1作为心血管等疾病生物标志物的最新研究进展进行了全面综述。