基于影像的形态学特征与胶质母细胞瘤特征分子表达的相关性研究

本文探讨了磁共振成像（MRI）形态学指标与胶质母细胞瘤（GBM）特征分子表达率的相关性,为GBM的临床评估、个性化治疗方案的选择及预后评价提供了影像学参考依据.首先回顾性分析了我院60例经手术病理证实的GBM的MRI数据,测量计算出肿瘤区最长径（TLD）、水肿区最长径（ELD）、强化与肿瘤长径比例（CTE/TLD）3个形态学指标.同时,进行免疫组化染色,得到GBM的表皮生长因子受体（EGFR）、异柠檬酸脱氢酶-1（IDH-1）、抑癌基因TP53、磷酸酶-张力蛋白（PTEN）和神经丝轻链（NEFL）特征性变化,根据染色程度与瘤细胞阳性细胞的比率的乘积进行评分.然后,对TLD、ELD和CTE/TLD与上述分子表达分别进行Pearson相关分析和多元logistic回归分析.结果标明TLD与EGFR、PTEN表达呈正相关（r=0.796、r=0.533）,与IDH-1表达呈负相关（r=-0.672）.CTE/TLD与EGFR、PTEN表达呈正相关（r=0.622、r=0.638）,与IDH-1表达呈负相关（r=-0.493）.ELD与5个特征分子的表达均无显著相关性.因此,基于MRI的肿瘤形态学分析能够在一定程度上反应肿瘤特征分子的差异,对GBM的分子分级和预后判断可提供直观的影像学参考依据.本文结果显示常规MRI测量肿瘤形态学指标有可能成为一种较为简便直观的胶质瘤分级与预后评估手段.     

纳米材料在用于癌症诊断的呼出气挥发性有机物检测中的应用

细胞新陈代谢的变化会导致挥发性有机化合物（VOCs）类型及含量发生变化,因此可通过分析某些标志性VOCs简立起多种疾病早期诊断的模型. 人体呼出物中特征VOCs的检测作为一种非侵入性、无损的检测手段,近些年在疾病检测领域已成为世界范围内的研究热点. 其中,纳米材料可用于增强传感器性能,并使传感器便携式小型化,推进检测传感器进入临床. 在这篇综述中,作者将种类繁多的传感器中用到的纳米材料归纳总结为金属、金属氧化物、碳基、复合物和MOFs基纳米材料等几类,并讨论了不同类纳米材料在VOCs检测中的优劣势. 本文所建立起的分析方法及讨论有助于进一步了解检测技术的优越性与局限性. 最后,作者对利用VOCs的检测实现癌症早期筛选的研究及发展提出了个人观点.     

Raman microspectrometric investigationof urea in calcite and gypsum powder matrices

Raman microspectrometry was used for the nondestructive detection of urea in artificially prepared mineral matrices. Various concentrations of urea, a possible biomarker, mixed with calcite and gypsum powders were analyzed using the 514.5‐nm line of an argon laser. Two types of measurements were carried out: direct measurements of powders and analysis of the same mixtures through natural, transparent crystals of calcite and gypsum. The detection limit for urea in artificial powder mixtures was 1 wt% for both calcite and gypsum. In the case of measurements through the monocrystals, the detection limit was between 1 and 5 wt% for calcite and slightly above 5 wt% in the case of gypsum. Copyright © 2010 John Wiley & Sons, Ltd.     

基于心磁信号的心脏电流偶极子阵列成像及相关性质的研究

超导量子干涉器（SQUID）能探测到微弱的心脏磁场信号. 通过对所得的心磁信号进行分析,可为许多心脏疾病的诊断提供依据. 利用心磁信号,采用极小范数最小二乘法（MNLS）对心脏的电流偶极子阵列进行重建,从而实现了对心脏内部等效电流源的成像. 在使用MNLS进行电流偶极子阵列反演重建的过程中,反演所需的心磁信号,分别由单电流偶极子和电流多极子作为激发源模拟得到,以及由SQUID实际测量得到. 同时,对不同心磁信号反演得到的电流偶极子的分布规律进行了分析. 此外,还给模拟的人体外心磁信号施加了均匀噪声和随机噪声,研究不同信噪比的均匀噪声和随机噪声对电流偶极子阵列重建的影响.     

Fabrication of a Colorimetric Carcino-Embryonic Antigen Sensor Using High-Activity DNAzyme as a Catalytic Label

Detection of biomarkers in a biologically complex mixture remains a major challenge. Herein, an ultrasensitive colorimetric sandwich sensor for carcino-embryonic antigen (CEA) detection is introduced. The DNAzyme was tethered to biotinylated monoclonal antibodies (McAbs) which serve as the sensing element to recognize the target protein and was then introduced on to the CEA-McAbs assembled micro plate. The CEA was captured in a sandwich assay by the McAbs. The peroxidase-like DNAzyme catalyzed the oxidation of 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid), which generated a blue-green colorimetric signal. This method detected CEA in a serum-containing medium at a concentration as low as 10 nM. This strategy is a promising tool for bioanalytical and clinical applications.     

Critical aspects of urine profiling for the selection of potential biomarkers using UPLC-TOF-MS

Biomarker selection through the metabolomics approach involves the acquisition of nontargeted metabolic profiles. In this study, some critical factors that may affect this process were investigated using urine test samples and a UPLC‐TOF system. Repeated injections of a single sample demonstrated that the percentage of undetected and poorly repeatable measurements (intensity RSD > 15%) decreased from 22.5 to 5.8% and from 32.9 to 14.7%, respectively, as the scan time was increased up to 0.6 s (approximately 11 data points per peak). An additional critical factor was identified in the presence of broad concentration differences between the samples; the application of a dilution scheme that minimized these differences reduced the number of missing values in the final datasets by 36%. The impact of missing values was further investigated in the study of two groups of samples produced by using a spike as artificial marker. Missing values weakened the models used for the interpretation of the metabolic profiles, and greatly hindered the identification of possible markers. Finally, a simple strategy for an effective analysis of urine samples was outlined; it proved to limit the need for the post‐acquisition elaboration of the data. The same strategy can easily be adapted to other matrices. Copyright © 2011 John Wiley & Sons, Ltd.     

Serum metabolomics as a novel diagnostic approach for gastrointestinal cancer

Conventional tumor markers are unsuitable for detecting carcinoma at an early stage and lack clinical efficacy and utility. In this study, we attempted to investigate the differences in serum metabolite profiles of gastrointestinal cancers and healthy volunteers using a metabolomic approach and searched for sensitive and specific metabolomic biomarker candidates. Human serum samples were obtained esophageal (n = 15), gastric (n = 11), and colorectal (n = 12) cancer patients and healthy volunteers (n = 12). A model for evaluating metabolomic biomarker candidates was constructed using multiple classification analysis, and the results were assessed with receiver operating characteristic curves. Among the 58 metabolites, the levels of nine, five and 12 metabolites were significantly changed in the esophageal, gastric and colorectal cancer patients, respectively, compared with the healthy volunteers. Multiple classification analysis revealed that the variations in the levels of malonic acid and l ‐serine largely contributed to the separation of esophageal cancer; gastric cancer was characterized by changes in the levels of 3‐hydroxypropionic acid and pyruvic acid; and l ‐alanine, glucuronoic lactone and l ‐glutamine contributed to the separation of colorectal cancer. Our approach revealed that some metabolites are more sensitive for detecting gastrointestinal cancer than conventional biomarkers. Our study supports the potential of metabolomics as an early diagnostic tool for cancer. Copyright © 2011 John Wiley & Sons, Ltd.     

LC-MS/MS method for the quantification of myo- and chiro-inositol as the urinary biomarkers of insulin resistance in human urine

A simple LC‐MS/MS method has been developed and validated for the quantification of endogenous myo‐ and chiro‐inositol in human urine. myo‐ and chiro‐Inositol were completely resolved from other carbohydrates and there were no interference peaks in human urine. The correlation coefficient (n = 3) was greater than 0.9991 over the range 0.05–25.0 µg/mL with the weighted (1/C²) least square method. Precision (%RSD) and accuracy (%RE) were 0–10.0% and 0–6.0% for the intra‐day assay (n = 5) and 0–14.3% and 0–10.0% for the inter‐day assay (n = 5). myo‐ and chiro‐Inositol have been shown to be stable in human urine stored at room temperature and for three freeze–thaw cycles. Copyright © 2011 John Wiley & Sons, Ltd.     

PSAQ™ standards for accurate MS–based quantification of proteins: from the concept to biomedical applications

Absolute protein quantification, i.e. determining protein concentrations in biological samples, is essential to our understanding of biological and physiopathological phenomena. Protein quantification methods based on the use of antibodies are very effective and widely used. However, over the last ten years, absolute protein quantification by mass spectrometry has attracted considerable interest, particularly for the study of systems biology and as part of biomarker development. This interest is mainly linked to the high multiplexing capacity of MS analysis, and to the availability of stable‐isotope‐labelled standards for quantification. This article describes the details of how to produce, control the quality and use a specific type of standard: Protein Standard Absolute Quantification (PSAQ?) standards. These standards are whole isotopically labelled proteins, analogues of the proteins to be assayed. PSAQ standards can be added early during sample treatment, thus they can correct for protein losses during sample prefractionation and for incomplete sample digestion. Because of this, quantification of target proteins is very accurate and precise using these standards. To illustrate the advantages of the PSAQ method, and to contribute to the increase in its use, selected applications in the biomedical field are detailed here. Copyright © 2012 John Wiley & Sons, Ltd.     

Neurodegeneration in Multiple Sclerosis: Symptoms of Silent Progression,Biomarkers and Neuroprotective Therapy—Kynurenines Are Important Players

Neurodegeneration is one of the driving forces behind the pathogenesis of multiple sclerosis (MS). Progression without activity, pathopsychological disturbances (cognitive impairment, depression, fatigue) and even optic neuropathy seems to be mainly routed in this mechanism. In this article, we aim to give a comprehensive review of the clinical aspects and symptomology, radiological and molecular markers and potential therapeutic targets of neurodegeneration in connection with MS. As the kynurenine pathway (KP) was evidenced to play an important role in the pathogenesis of other neurodegenerative conditions (even implied to have a causative role in some of these diseases) and more and more recent evidence suggest the same central role in the neurodegenerative processes of MS as well, we pay special attention to the KP. Metabolites of the pathway are researched as biomarkers of the disease and new, promising data arising from clinical evaluations show the possible therapeutic capability of KP metabolites as neuroprotective drugs in MS. Our conclusion is that the kynurenine pathway is a highly important route of research both for diagnostic and for therapeutic values and is expected to yield concrete results for everyday medicine in the future.