简介：Inanattempttoassessthepaleoenvironmentsofterrestrialsediments,sometwenty-tworepresenta-tiveChinesenon-marinesedimentsampleswerestudiedusingthemolecularorganicgeochemistrymethod.Thesedimentsamplesstuiedincludeoilshale,shale,mudstoneandglaubersaltfromTertiarytoCretaceousinage.Judgingfromgeological/geochemicaldataandpaleosalinitydata,thesamplesstudiedareoflacustrinesedimentaryoriginandcanbedividedintothreedifferenttypes:freshwater,brackishandsaline/hypersalinelakesediments.ThealiphaticfractionswereseparatedfromtheextractsofthesamplesandanalysedbymeansofGCandGC/MSinstruments,givinganumberofparameterssuchasrelativeabundancesofalkanesandcycloalkanesasshowninthemasschromatograms.

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简介：AbstractPancreatic neuroendocrine tumors (pNET) are heterogenous tumors originated from the diffuse neuroendocrine cells of pancreas, which show the function of synthesis, storage and secretion of peptide hormones and biomimetic amines. Biomarkers play a crucial role in the diagnosing, evaluating prognosis and predicting treatment response for pNET patients. Traditional NET markers such as chromogranin A and Neuron Specific Enolase, as a diagnostic biomarker, have relatively low sensitivity and specificity in pNET patients. The emergence of new types of biomarkers provides more reliable indicators for diagnosis and prognosis evaluation. Among them, NETest score is a promising biomarker with the highest diagnostic sensitivity (80%) and specificity (94%). In addition, this molecule can be also used as a prognostic biomarker, which can predict disease progression and shorter overall survival. Biomarkers related to therapeutic targets, such as vascular endothelial growth factor, vascular endothelial growth factor receptor, and key molecules of mTOR signaling pathway, have capability to predict response of treatment. With the development of next-generation sequencing, chip array, and digital droplet PCR, novel biomarkers such as circulating tumor cells, tumor-derived exosomes, and circulating tumor DNA and mRNA are expected to provide more accurate diagnosis, prognostic information, and prospective therapeutic targets. In this paper, biomarkers of pancreatic neuroendocrine tumor and their role in diagnosis, prognosis, diagnosis, treatment and monitoring are systematically introduced. Our conclusions can provide new basis for clinicians in the diagnosis and treatment process.

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简介：Epithelialovariancancer(EOC)istheleadingcauseofdeathamongallgynecologicalmalignancies.Despitethetechnologicalandmedicaladvancesoverthepastfourdecades,suchasthedevelopmentofseveralbiologicalmarkers(mRNAandproteinsbiomarkers),themortalityrateofovariancancerremainsachallengebecauseofitslatediagnosis,whichisspecificallyattributedtolowspecificitiesandsensitivities.Underthiscompulsivescenario,recentadvancesinexpressionbiologyhaveshiftedinidentifyinganddevelopingspecificandsensitivebiomarkers,suchasmicroRNAs(miRNAs)forcancerdiagnosisandprognosis.MiRNAsareanovelclassofsmallnon-codingRNAsthatderegulategeneexpressionattheposttranscriptionallevel,eitherbytranslationalrepressionorbymRNAdegradation.Thesemechanismsmaybeinvolvedinacomplexcascadeofcellulareventsassociatedwiththepathophysiologyofmanytypesofcancer.MiRNAsareeasilydetectableintissueandbloodsamplesofcancerpatients.Therefore,miRNAsholdgoodpromiseaspotentialbiomarkersinovariancancer.Inthisreview,weattemptedtoprovideacomprehensiveprofileofkeymiRNAsinvolvedinovariancarcinomatoestablishmiRNAsasmorereliablenon-invasiveclinicalbiomarkersforearlydetectionofovariancancercomparedwithproteinandDNAbiomarkers.

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简介：AbstractBackground:Deregulation of miRNA-21 expression has been reported to be associated with vascular smooth muscle behavior and cytoskeletal stability. This study is aimed to investigate the density of serum miRNA-21 in patients with different phases of intracranial aneurysms (IAs) and explore its warning function for IA rupture.Methods:A total of 16 in 200 IA patients were selected and categorized into 4 groups based on the phase of IA. Microarray study was carried out using serum miRNA and differentially expressed miRNAs were identified. Another 24 samples from a cohort of 360 patients were added and real-time polymerase chain reaction (RT-PCR) was performed on expanded sample size (n = 40) for miRNA-21 validation. Potential gene targets of miRNA-21 were screened out from Gene Ontology (GO) database and literatures.Results:Microarray study identified 77 miRNAs with significantly different expression levels between experimental groups and the control group. RT-PCR assays validated significant downregulation of miRNA-21 in experimental groups, among which miRNA-21 expression level of daughter aneurysm group decreased the most. Bioinformatic analyses revealed that several target genes related with miRNA-21 may be involved in IA formation and rupture.Conclusions:This study suggested that miRNA-21 had a protective effect for intracranial vascular wall against remodeling and warning function for intracranial aneurysm rupture. Significant suppression of serum miRNA-21 in IA patients may provide diagnostic clues for aneurysm rupture and guide clinical intervention.

简介：多肽和蛋白质与多种疾病，如癌症，糖尿病，神经疾病和心血管疾病等有关。从各种生理、病理样品中找出相关的疾病标志蛋白，将有助于新型药物靶标的发现、疾病的早期诊断及新疗法的开发。各种疾病蛋白质指纹谱的发现及深入研究，是当前蛋白质组学的前沿研究领域。结合新型的膜修饰技术及专有的化学洗脱方法，PerkinElmer公司新近推出两种生物标志蛋白富集试剂盒：低通量人工操作型，可处理10个样品；

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简介：AbstractBackground:According to the amyloid, tau, neurodegeneration research framework classification, amyloid and tau positive (A+T+) mild cognitive impairment (MCI) individuals are defined as prodromal Alzheimer disease. This study was designed to compare the clinical and biomarker features between A+T+MCI individuals who progressed to progressive MCI (pMCI) and those who remained stable MCI (sMCI), and to identify relevant baseline clinical biomarker and features that could be used to predict progression to dementia within 2 years.Methods:We stratified 197 A+T+MCI individuals into pMCI (n = 64) and sMCI (n = 133) over 2 years. Demographics and cognitive assessment scores, cerebrospinal fluid (CSF), and neuroimaging biomarkers (18F-florbetapir positron emission tomography mean standardized uptake value ratios [SUVR] and structural magnetic resonance imaging [MRI]) were compared between pMCI and sMCI at baseline, 12- and 24-month follow-up. Logistic regression models then were used to evaluate clinical baseline and biomarker features that predicted dementia progression in A+T+MCI.Results:pMCI individuals had higher mean 18F-florbetapir SUVR, CSF total-tau (t-tau), and p-tau181P than those in sMCI individuals. pMCI individuals performed poorer in cognitive assessments, both global and domain specific (memory, executive, language, attention, and visuospatial skills) than sMCI. At baseline, there were significant differences in regions of interest of structural MRI between the two groups, including bilateral amygdala, hippocampus and entorhinal, bilateral inferior lateral ventricle, left superior and middle temporal, left posterior and caudal anterior cingulate (P < 0.05). Baseline CSF t-tau levels and cognitive scores of Montreal cognitive assessment, functional assessment questionnaire, and everyday cognition by the patient’s study partner language domain could predict progression to dementia in A+T+MCI within 2 years.Conclusions:In future clinical trials, specific CSF and cognitive measures that predict dementia progression in A+T+MCI might be useful risk factors for assessing the risk of dementia progression.

简介：AbstractBackground:Psoriatic arthritis (PsA) is an inflammatory arthropathy characterized by psoriasis and bone erosion on radiology. Dickkopf-1 (Dkk-1) is considered to be the main inhibitor of the Wnt signaling pathway and results in reduced osteoblast proliferation. The aim of this study was to investigate the serum level of Dkk-1 and its association with bone erosion in PsA patients.Methods:Serum Dkk-1 levels were measured by enzyme-linked immunosorbent assay (ELISA) in 69 patients with PsA and 60 controls, including 39 rheumatoid arthritis (RA) patients, and 21 healthy controls (HCs). Rheumatoid factor and anti-cyclic citrullinated peptide levels were also determined by ELISA. The association of Dkk-1 level with clinical and laboratory features of PsA was analyzed. Logistic regression analysis was used to analyze the risk factors for bone erosion in PsA.Results:Dkk-1 was elevated in 68.1% (47/69) of the patients with PsA, 46.2% (18/39) of RA patients, and 9.5% (2/21) of HCs. Serum Dkk-1 concentration was significantly higher in PsA patients compared with that in HCs. The level of serum Dkk-1 was correlated with a swollen joint count, and levels of complement components 3 and 4. Elevated Dkk-1 level (odds ratio = 4.440, 95% confidence interval: 1.246-15.817, P = 0.021) was identified as the risk factor for bone erosion in PsA.Conclusions:The serum level of Dkk-1 is abnormally elevated in PsA patients. The elevation of Dkk-1 might be involved in the mechanism of bone erosion in patients with PsA.

简介：AbstractBackground:Gliomas are the most common primary malignant brain tumors and have a poor prognosis. Early detection of gliomas is crucial to improve patient outcomes. Urine accumulates systematic body changes and thus serves as an excellent early biomarker source.Methods:At the biomarker discovery phase, we performed a self-controlled proteomics analysis by comparing urine samples collected from five glioma patients at the time of tumor diagnosis and after surgical removal of the tumor. At the biomarker validation phase, we further validated some promising proteins using parallel reaction monitoring (PRM)-based targeted proteomics in another cohort, including glioma, meningioma, and moyamoya disease patients as well as healthy controls.Results:Using label-free proteome quantitation (LFQ), we identified twenty-seven urinary proteins that were significantly changed after tumor resection, many of which have been previously associated with gliomas. The functions of these proteins were significantly enriched in the autophagy and angiogenesis, which are associated with glioma development. After targeted proteomics validation, we identified a biomarker panel (AACT, TSP4, MDHM, CALR, LEG1, and AHSG) with an area under the curve (AUC) value of 0.958 for the detection of gliomas. Interestingly, AACT, LEG1, and AHSG are also potential cerebrospinal fluid or blood biomarkers of gliomas.Conclusions:Using LFQ and PRM proteome quantification, we identified candidate urinary protein biomarkers with the potential to detect gliomas. This study will also provide clues for future biomarker studies involving brain diseases.

简介：AbstractBackground:Accumulating evidence has revealed that circulating microRNAs (miRNAs) can serve as non-invasive biomarkers for cancer diagnosis. This study aimed to identify differentially expressed miRNAs in serum which might become potential biomarkers for non-invasive diagnosis of papillary thyroid carcinoma (PTC).Methods:The experiment was carried out between 2015 and 2017. In the screening stage, the Exiqon miRNA quantitative real-time polymerase chain reaction (qPCR) panel was applied to select candidate miRNAs. In the following training, testing, and external validation stages, the serum samples of 100 patients and 96 healthy controls (HCs) were analyzed to compare the expression levels of the identified miRNAs. The areas under the receiver operating characteristic curves (AUCs) were calculated to assess the diagnostic value of the identified signature.Results:Three miRNAs (miR-25-3p, miR-296-5p, and miR-92a-3p) in serum were consistently up-regulated in PTC patients compared with HCs. A three-miRNA panel was constructed by logistic regression analysis and showed better diagnostic performance than a single miRNA for PTC detection. The AUCs of the panel were 0.727, 0.771, and 0.862 for the training, testing, and external validation stage, respectively. Meanwhile, the panel showed stable capability in differentiating PTC patients from patients with benign goiters, with an AUC as high as 0.969. For further exploration, the three identified miRNAs were analyzed in tissue samples (23 PTC vs. 23 HCs) and serum-derived exosomes samples (24 PTC vs. 24 HCs), and the altered expression in the tumor also indicated their close relationship with PTC disease.Conclusion:We identify a three-miRNA panel in serum which might serve as a promising biomarker for PTC diagnosis.

简介：AbstractBackground:Low-grade gliomas (LGG) are WHO grade II tumors presenting as the most common primary malignant brain tumors in adults. Currently, LGG treatment involves either or a combination of surgery, radiation therapy, and chemotherapy. Despite the knowledge of constitutive genetic risk factors contributing to gliomas, the role of single genes as diagnostic and prognostic biomarkers is limited. The aim of the current study is to discover the predictive and prognostic genetic markers for LGG.Methods:Transcriptome data and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. We first performed the tumor microenvironment (TME) survival analysis using the Kaplan-Meier method. An analysis was undertaken to screen for differentially expressed genes. The function of these genes was studied by Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Following which a protein-protein interaction network (PPI) was constructed and visualized. Univariate and multivariate COX analyses were performed to obtain the probable prognostic genes. The key genes were selected by an intersection of core and prognostic genes. A clinical correlation analysis of single-gene expression was undertaken. GSEA enrichment analysis was performed to identify the function of key genes. Finally, a single gene-related correlation analysis was performed to identify the core immune cells involved in the development of LGG.Results:A total of 529 transcriptome data and 515 clinical samples were obtained from the TCGA. Immune cells and stromal cells were found to be significantly increased in the LGG microenvironment. The top five core genes intersected with the top 38 prognostically relevant genes and two key genes were identified. Our analysis revealed that a high expression of HLA-DRA was associated with a poor prognosis of LGG. Correlation analysis of immune cells showed that HLA-DRA expression level was related to immune infiltration, positively related to macrophage M1 phenotype, and negatively related to activation of NK cells.Conclusions:HLA-DRA may be an independent prognostic indicator and an important biomarker for diagnosing and predicting survival in LGG patients. It may also be associated with the immune infiltration phenotype in LGG.

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简介：AbstractBackground:Fibrosis in the peripheral airways contributes to airflow limitation in patients with chronic obstructive pulmonary disease (COPD). However, the key proteins involved in its development are still poorly understood. Thus, we aimed to identify the differentially expressed proteins (DEPs) between smoker patients with and without COPD and elucidate the molecular mechanisms involved by investigating the effects of the identified biomarker candidate on lung fibroblasts.Methods:The potential DEPs were identified by isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic analysis. The messenger RNA and protein levels of clusterin (CLU) in COPD patients and 12% cigarette smoke extract (CSE)-treated human bronchial epithelial cells were determined at the indicated time points. Furthermore, an in vitro COPD model was established via the administration of 8% CSE to normal human lung fibroblasts (NHLFs) at indicated time points. The effects of CSE treatment and CLU silencing on proliferation and activation of lung fibroblasts were analyzed.Results:A total of 144 DEPs were identified between COPD patients and normal smokers. The iTRAQ-based proteomics and bioinformatics analyses identified CLU as a serum biomarker candidate. We also discovered that CLU levels were significantly increased (P < 0.0001) in Global Initiative for Obstructive Lung Disease II, III, and IV patients and correlated (P < 0.0001) with forced expiratory volume in 1 s (R=-0.7705), residual volume (RV) (R = 0.6281), RV/total lung capacity (R = 0.5454), and computerized tomography emphysema (R = 0.7878). Similarly, CLU levels were significantly increased in CSE-treated cells at indicated time points (P < 0.0001). The CSE treatment significantly inhibited the proliferation, promoted the inflammatory response, differentiation of NHLFs, and collagen matrix deposition, and induced the apoptosis of NHLFs; however, these effects were partially reversed by CLU silencing.Conclusion:Our findings suggest that CLU may play significant roles during airway fibrosis in COPD by regulating lung fibroblast activation.

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简介：客观联系XIAP的因素1(XAF1)表示被显示了与在hepatocellular癌(HCC)的apoptosis相关。然而，有HCC肿瘤等级的XAF1表示的关联强烈地没被估计。联系XIAP的factor-1(XAF1)是在人的HCC的重要apoptosisinducer。这研究的目的是决定在XAF1表示和HCC组织病理学说的等级之间的关联。