IL-21 Enhances the Immune Protection Induced by the Vibrio vulnificus Hemolysin A Protein.

We previously reported that the Vibrio vulnificus hemolysin A (VvhA) protein elicited good immune protection and could effectively control V. vulnificus infection in mice. However, its molecular mechanism remains unknown. We hypothesized that hemolysin A induces an immunoprotective response via IL-21 regulation. To demonstrate this, IL-21 expression in mice was regulated by injecting either specific antibodies or rIL-21, and the immune response was evaluated by flow cytometry. Our results suggested that IL-21 enhances immune protection by inducing a T follicular helper cell and germinal center B cell response. We used RNA-seq to explore molecular mechanisms and identified 10 upregulated and 32 downregulated genes involved in IL-21-upregulated protection. Gene Ontology analysis and pathway analysis of the differentially expressed genes were also performed. Our findings indicate that IL-21 can enhance the immune protection effect of the VvhA protein and may serve as a novel strategy for enhancing the immune protection effect of protein vaccines.

MALDI-TOF-MS analysis in low molecular weight serum peptidome biomarkers for NSCLC.

OBJECTS: Lung cancer is one of the leading causes of death from cancer in the world. Screening new serum biomarkers is important for the early detection of lung cancer. The purpose of this study was to investigate the serum peptide model between non-small cell lung cancer (NSCLC) patients and healthy controls, as well as between paired pre- and postoperative NSCLC patients, and to find the low molecular weight (LMW) potential tumor markers for NSCLC. METHODS: 56 serum samples from NSCLC patients, 56 controls, and 20 matched pre- and postoperative patients were analyzed using magnetic-bead (MB)-based purification technique combined with MALDI-TOF-MS. To distinguish NSCLC from cancer-free controls, three models were established. Finally, comparing the three groups of serum protein fingerprints, nano-liquid chromatography-electrospray ionization tandem mass spectrometry was used to further identify the differential peptides. RESULTS: Among the three models constructed, the GA model had the best diagnostic efficacy. Five differential peaks were screened by combining the case group, healthy controls, and postoperative group analysis, which were up-regulated in the case group and showed a tendency to return to healthy control values after surgery. The protein matching the mass spectrometry peak m/z 2953.73 was identified as fibrinogen α chain. CONCLUSION: This study shows that the application of MALDI-TOF-MS is a promising approach for the identification of potential serum biomarkers for NSCLC, which is potentially valuable for establishing a new diagnostic method for lung cancer. In addition, we found that fibrinogen α chain may be an auxiliary diagnostic indicator for NSCLC.

Chinese Expert Consensus on the Nucleic Acid Detection of SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) has already become a pandemic wherein the infection's timely diagnosis has proven beneficial to patient treatment and disease control. Nucleic acid detection has been the primary laboratory diagnostic method for the detection of SARS-CoV-2. To ensure laboratory staff safety and quality nucleic acid testing, the Chinese Society of Laboratory Medicine formulated this consensus, based on the Chinese National Recommendations and previous literature for nucleic acid detection. A working group comprises 34 hospital professionals experience with real-time polymerase chain reactions (PCR) testing for SARS-CoV-2 drafted guidance statements during online discussions. A modified Delphi methodology was used in forming a consensus among a wider group of hospital professionals with SARS-CoV-2 detection experience. Guidance statements were developed for four categories: (I) specimen type, priority, collecting, transportation and receiving; (II) nucleic acid isolation and amplification; (III) quality control; (IV) biosafety management and decontamination. The modified Delphi voting process included a total of 29 guidance statements and final agreement. Consensus was reached after two rounds of voting. Recommendations were established for the detection of SARS-CoV-2 using real time PCR testing based on evidence and group consensus. The manuscript was evaluated against The Appraisal of Guidelines for Research & Evaluation Instrument (AGREE II) and was developed to aid medical laboratory staff in the detection of the ribonucleic acid (RNA) of SARS-CoV-2.

Detection and Identification of Serum Peptides Biomarker in Papillary Thyroid Cancer.

BACKGROUND Papillary thyroid cancer (PTC) is currently the most commonly diagnosed endocrine malignancy. In addition, the sex- and age-adjusted incidence of PTC has exhibited a greater increase over the last 2 decades than in many other malignancies. Thus, discovering noninvasive specific serum biomarker to distinguish PTC from cancer-free controls in its early stages remains an important goal. MATERIAL AND METHODS Serum samples from 88 PTC patients and 80 cancer-free controls were randomly allocated into training or validation sets. Serum peptide profiling was performed by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS) after using weak cation exchange magnetic beads (WCX-MB), and the results were evaluated by use of ClinProTools™ Software. To distinguish PTC from cancer-free controls, quick classifier (QC), supervised neural network (SNN), and genetic algorithm (GA) models were established. The models were blindly validated to verify their diagnostic capabilities. The most discriminative peaks were subsequently identified with a nano-liquid chromatography-electrospray ionization-tandem mass spectrometry system. RESULTS Six peptide ions were identified as the most discriminative peaks between the PTC and cancer-free control samples. The QC model exhibited satisfactory sensitivity and specificity among the 3 models that were validated. Two peaks, at m/z 2671.17 and m/z 1464.68, were identified as fragments of the alpha chain of fibrinogen, while a peak at m/z 1738.92 was a fragment of complement component 4A/B. CONCLUSIONS MS combined with ClinProTools™ software was able to detect peptide biomarkers in PTC patients. In addition, the constructed classification models provided a serum peptidome pattern for distinguishing PTC from cancer-free controls. Both fibrinogen a and complement C4A/B were identified as potential markers for diagnosis of PTC.

Diagnostic accuracy of MALDI-TOF mass spectrometry for non-small cell lung cancer: a meta-analysis.

Objective: To assess the overall accuracy of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in identifying non-small cell lung cancer (NSCLC).Methods: A comprehensive search of PubMed, EMBASE and CNKI databases as well as the reference lists from relevant articles was performed prior to July 2017. Two authors independently screened articles based on inclusion and exclusion criteria and assessed the quality of each study using the Quality Assessment of Diagnostic Accuracy Studies 2 (QADAS-2) tool. Meta-disc 1.4 and Stata12.0 software programs were used for the statistical analysis.Results: Eleven eligible articles comprising 16 studies and representing 935 subjects were included in this meta-analysis. The pooled sensitivity and specificity were 0.84 (95% CI: 0.80-0.87) and 0.77 (95% CI: 0.74-0.80), respectively. The overall diagnostic performance as measured by the area under the curve (AUC) for the summary receiver-operating characteristic (SROC) curve was 0.9380.Conclusions: MALDI-TOF MS has a high diagnostic accuracy for NSCLC.

Direct Detection of Vibrio vulnificus, Vibrio parahaemolyticus, and Vibrio alginolyticus from Clinical and Environmental Samples by a Multiplex Touchdown Polymerase Chain Reaction Assay.

BACKGROUND: Vibrio vulnificus, V. alginolyticus, and V. parahaemolyticus are commonly and opportunistically pathogenic to humans. METHODS: In this study, a novel multiple touchdown polymerase chain reaction method (MT-PCR) was developed to benefit rapid and simultaneous detection of the presence of the three Vibrio species from the enriched clinical and environmental samples. RESULTS: The method showed a sensitivity of 104 colony forming units (CFU)/mL for V. vulnificus, 103 CFU/mL for V. parahaemolyticus and V. alginolyticus, and a specificity of 100% for all the three Vibrio species. All strains of the three Vibrio species were detected in the spiked samples artificially contaminated with reference strains and were identified directly from the enriched clinical and environmental samples within three hours by this MT-PCR assay. All the corresponding bacteria were isolated from these enriched samples in 48 hours by standard microbiologic procedures. CONCLUSIONS: This MT-PCR method, which can detect V. vulnificus, V. parahaemolyticus, and V. alginolyticus directly and simultaneously, was rapid, sensitive, specific, and can be used in clinical diagnostics, food industry studies, and risk assessment of environment.

Vibrio vulnificus VvhA induces Th1 and Tfh cells to proliferate against Vibrio vulnificus in a mouse model of infection.

AIM: To characterize the roles of VvhA in host's acquired immune response to Vibrio vulnificus infection. MATERIALS & METHODS: The recombinant VvhA fusion protein was used to immunize mice and the anti-VvhA polyclonal antibody was produced in vivo for prophylactic and therapeutic efficacy assay. The roles of VvhA in T helper (Th) cells differentiation were analyzed by vvhA-deleted mutant during the early phase of infection, while the ratio of Th2 and T follicular helper (Tfh) cells were examined in VvhA immunization. RESULTS: Anti-VvhA antibody exhibited neutralization activity against V. vulnificus. Wild-type strain induced higher level of Th1 cells than the mutant, and the concentrations of IgG2a and IFN-γ were increased during the early phase of infection. The spontaneous development of Tfh was observed in immunized model, and the serum IL-21 was increased. CONCLUSION: V. vulnificus VvhA elicited cellular and humoral immune responses by Th1 and Tfh cells to provide protection against VvhA.

Upregulation of kallikrein­related peptidase 5 is associated with the malignant behavior of colorectal cancer.

Kallikrein-related peptidase 5 (KLK5) is a serine protease that has exhibited upregulated expression in numerous types of human cancer. The present study assessed KLK5 expression in colorectal cancer (CRC) tissues, in order to determine its association with clinicopathological data and prognosis. The mRNA and protein expression levels of KLK5 were detected using reverse transcription­quantitative polymerase chain reaction, immunohistochemistry and enzyme­linked immunosorbent assay, respectively. KLK5 expression was detected in 48 paraffin­embedded tumor tissue samples and corresponding tumor­free areas within the same specimens, 40 paired normal and CRC frozen tissues, and serum samples from 70 patients with CRC (including 38 serum samples taken pre­ and post­surgery) and 53 healthy individuals. The results demonstrated that KLK5 protein was strongly expressed in CRC; however, its expression was hardly detected in the matched normal mucosal tissue. The KLK5 mRNA expression levels were significantly upregulated in CRC tissues compared with the paired normal tissues, and were higher in Dukes' stage C/D cancer than in stage A/B (P<0.001). Furthermore, sera from patients with CRC exhibited increased KLK5 levels, as compared with that of healthy volunteers (878.02 vs. 391.07 pg/ml; P<0.001). Serum KLK5 levels were also significantly higher in patients prior to surgery compared with post­surgery (909.48±536.72 vs. 644.00±522.87 pg/ml; P<0.001). In addition, increased serum KLK5 levels were associated with CRC lymph node or distant metastasis (P=0.003), tumor­lymph node­metastasis stage (P=0.004), and Dukes' stage (P=0.005). The results of the present study indicated that the mRNA and protein expression levels of KLK5 were significantly upregulated in CRC tissues and sera, and were associated with an advanced tumor stage. Further studies may identify KLK5 as a biomarker of CRC recurrence or treatment response.

Diagnostic value of KLK6 as an ovarian cancer biomarker: A meta-analysis.

Kallikrein-related peptidase 6 (KLK6) is a new potential serum biomarker of ovarian cancer. The aim of the present study was to assess the diagnostic value of KLK6 systematically for ovarian cancer. All the selected studies regarding the changes of KLK6 in ovarian cancer were published prior to April 2015. Five studies involving 485 patients with ovarian cancer, 420 benign cysts and 245 healthy controls met the inclusion criteria. The value of sensitivity, specificity, positive-likelihood ratio (LR+), negative-likelihood ratio (LR-) and area under the receiver operating characteristic curve (ROC) were obtained. All these indices were used to evaluate the diagnostic value of KLK6 for ovarian cancer. The values of sensitivity, specificity, LR+ and LR- (95% confidence interval) of KLK6 were 0.50 (0.47-0.54), 0.91 (0.89-0.93), 7.20 (3.34-15.52) and 0.51 (0.43-0.62), respectively. The area under the summary ROC of KLK6 was 0.86. The index of Q* was 0.79. In conclusion, KLK6 showed high specificity for the diagnosis of ovarian cancer. It can improve the diagnostic accuracy of cancer antigen 125 (CA125). A combined panel of CA125 and KL K6 shows a high diagnostic efficiency for advanced ovarian cancer. Owing to the small number of studies and lack of samples, additional studies meeting the inclusion criteria are required to further analyze the diagnostic value of KLK6 for ovarian cancer.

Serum Metabolomics to Identify the Liver Disease-Specific Biomarkers for the Progression of Hepatitis to Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common malignancy that has region specific etiologies. Unfortunately, 85% of cases of HCC are diagnosed at an advanced stage. Reliable biomarkers for the early diagnosis of HCC are urgently required to reduced mortality and therapeutic expenditure. We established a non-targeted gas chromatography-time of flight-mass spectrometry (GC-TOFMS) metabolomics method in conjunction with Random Forests (RF) analysis based on 201 serum samples from healthy controls (NC), hepatitis B virus (HBV), liver cirrhosis (LC) and HCC patients to explore the metabolic characteristics in the progression of hepatocellular carcinogenesis. Ultimately, 15 metabolites were identified intimately associated with the process. Phenylalanine, malic acid and 5-methoxytryptamine for HBV vs. NC, palmitic acid for LC vs. HBV, and asparagine and ß-glutamate for HCC vs. LC were screened as the liver disease-specific potential biomarkers with an excellent discriminant performance. All the metabolic perturbations in these liver diseases are associated with pathways for energy metabolism, macromolecular synthesis, and maintaining the redox balance to protect tumor cells from oxidative stress.

Liraglutide protects pancreatic ß-cells against free fatty acids in vitro and affects glucolipid metabolism in apolipoprotein E-/- mice by activating autophagy.

The aim of the present study was to determine whether liraglutide (LRG), a long acting glucagon-like peptide 1 analogue, exerted a protective effect on free fatty acid (FFA)­treated pancreatic ß­cells via activating autophagy. INS­1 insulinoma pancreatic islet cell lines were treated with FFA and the levels of cell necrosis, apoptosis and autophagy were detected using an MTT assay, flow cytometry and electron microscopy (ECM). A type 2 diabetes mellitus mouse model was established through treatment of mice with a high­fat diet for 8 weeks and injection of streptozotocin. LRG and autophagy inhibitors were used to investigate the protective effect of LRG on pancreatic ß­cells in vivo. Metabolic indices were measured and pancreatic autophagy was detected. In the INS­1 cells, viability was higher in the FFA + LRG group compared with the FFA group, while the apoptotic rate was lower (P<0.05). The light chain 3B and p62 autophagy­associated proteins were upregulated by LRG, while ATG7 and Beclin1 were downregulated. Autophagy inhibitors reduced the protective effect of LRG in the FFA­treated INS­1 cells. The type 2 diabetes mouse model was successfully established, termed the HF group, in which LRG was observed to reduce body weight and decrease levels of fasting blood glucose, total cholesterol, serum insulin, triglyceride, low density lipoprotein­cholesterol and glycosylated hemoglobin (P<0.05), compared with the HF group. However, chloroquine treatment abrogated these effects (P<0.05, compared with the HF + LRG group; P>0.05, compared with the HF group). Autophagosomes were also observed under ECM in the pancreatic tissues of mice in the HF + LRG group. Therefore, LRG induced autophagy and exerted protective effects on pancreatic ß-cells in vitro and in vivo.

Identification of Novel Inflammatory Cytokines and Contribution of Keratinocyte-Derived Chemokine to Inflammation in Response to Vibrio vulnificus Infection in Mice.

Currently, only tumor necrosis factor alpha (TNF-α) and interleukin family cytokines have been found to be elicited in Vibrio vulnificus (V. vulnificus)-infected animal models and humans. However, multiple other cytokines are also involved in the immune and inflammatory responses to foreign microorganism infection. Antibody array technology, unlike traditional enzyme-linked immunosorbent assay (ELISA), is able to detect multiple cytokines at one time. Therefore, in this study, we examined the proinflammatory cytokine profile in the serum and liver homogenate samples of bacterial-infected mice using antibody array technology. We identified nine novel cytokines in response to V. vulnificus infection in mice. We found that keratinocyte-derived chemokine (KC) was the most elevated cytokine and demonstrated that KC played a very important role in the V. vulnificus infection-elicited inflammatory response in mice, as evidenced by the fact that the blocking of KC by anti-KC antibody reduced hepatic injury in vivo and that KC induced by V. vulnificus infection in AML-12 cells chemoattracted neutrophils. Our findings implicate that KC may serve as a novel diagnostic biomarker and a possible therapeutic target for V. vulnificus infection.

Meta-analysis: diagnostic accuracy of anti-cyclic citrullinated peptide antibody for juvenile idiopathic arthritis.

OBJECTIVE: To estimate the diagnostic accuracy of the anti-CCP test in JIA and to evaluate factors associated with higher accuracy. METHODS: Two investigators performed an extensive search of the literature published between January 2000 and January 2014. The included articles were assessed by the Quality Assessment of Diagnostic Accuracy Studies tool. The meta-analysis was performed using a summary ROC (SROC) curve and a bivariate random-effect model to estimate sensitivity and specificity across studies. RESULTS: The bivariate meta-analysis yielded a pooled sensitivity and specificity of 10% (95% confidence interval (CI): 6.0%-15.0%) and 99.0% (95% CI: 98.0%-100.0%). The area under the SROC curve was 0.96. Sensitivity estimates were highly heterogeneous, which was partially explained by the higher sensitivity in the rheumatoid factor-positive polyarthritis (RF+ PA) subtype (48.0%; 95% CI: 31.0%-65.0%) than in the other subtypes (17.0%; 95% CI: 14.0%-20.0%) and the higher sensitivity of the Inova assay (17.0%; 95% CI: 14.0%-20.%%) than the other assays (0.05%; 95% CI: 2.0%-11.0%). CONCLUSIONS: Anti-CCP antibody test has a high specificity for the diagnosis of JIA. The sensitivity of this test is low and varies across populations but is higher in RF+ PA than in other JIA subtypes.

Complete Genome Sequence of Vibrio alginolyticus ATCC 17749T.

Vibrio alginolyticus is a Gram-negative halophilic bacterium and has been recognized as an opportunistic pathogen in both humans and marine animals. It is the causative agent of food-borne diseases, such as gastroenteritis, and it invades through wounds in predisposed individuals. In this study, we present the completed genome of V. alginolyticus ATCC 17749(T) through high-throughput sequencing.

Diagnostic accuracy of fecal lactoferrin for inflammatory bowel disease: a meta-analysis.

OBJECTIVE: To do a systematic review using meta-analysis to assess the diagnostic accuracy of fecal lactoferrin (FL) in patients with inflammatory bowel disease (IBD). METHODS: We performed a literature review and systematically searched the Medline and EMBASE databases for eligible studies. The quality of the included studies was assessed using the QUADAS tool. The sensitivity, specificity, and other diagnostic indexes of FL were pooled using a random-effects model. RESULTS: Seven studies, involving 1816 patients, met the inclusion criteria. In all studies, the pooled FL sensitivity and pooled specificity were 0.82 (95% confidence interval [CI]: 0.72, 0.89) and 0.95 (95% CI: 0.88, 0.98), respectively. The positive and negative likelihood ratios were 16.63 and 0.18, respectively. The area under the summary receiver-operating characteristic curve (SROC) was 0.95 (95% CI: 0.93, 0.97), and the diagnostic odds ratio was 90.04 (95% CI: 37.01, 219.02). The pooled FL sensitivity and specificity for Crohn's disease (CD) diagnosis (sensitivity =75%, specificity =100%) was not as good as it was for ulcerative colitis (UC) diagnosis (sensitivity =82%, specificity =100%). CONCLUSION: FL, as a noninvasive and screening marker, has a high specificity and a modest specificity during the diagnosis of suspected IBD.

Diagnostic value of total plasma lysophosphatidic acid in ovarian cancer: a meta-analysis.

OBJECTIVE: This study aimed to assess the diagnostic value of lysophosphatidic acid (LPA) in ovarian cancer. METHODS: A systematic review of related studies was performed; sensitivity, specificity, and other measures about the accuracy of serum LPA in the diagnosis of ovarian cancer were pooled using random-effects models. Summary receiver operating characteristic curve analysis was used to summarize the overall test performance. RESULTS: Six studies involving 363 patients with ovarian cancer and 273 healthy control women met the inclusion criteria. The summary estimates for LPA in diagnosing ovarian cancer in the included studies were as follows: sensitivity, 0.94 [95% confidence interval (CI), 0.91-0.96]; specificity, 0.88 (95% CI, 0.83-0.91); and diagnostic odds ratio, 141.59 (95% CI, 52.1-384.63). The area under the curve and Q value for summary receiver operating characteristic curves were 0.97 and 0.92, respectively. CONCLUSIONS: The LPA assay showed high accuracy and sensitivity for the diagnosis of ovarian cancer. The present study was limited by the small number of available studies and sample size; therefore, additional studies with a better design and larger samples are needed to further assess the diagnostic accuracy of LPA.

Correlation between KLK6 expression and the clinicopathological features of glioma.

AIM OF THE STUDY: We measured the impact of changing KLK6 expression levels on the pathological grade of gliomas and on proliferation rate, cell cycle progression, and apoptosis in the U251 glioblastoma cell line. MATERIAL AND METHODS: The expression of KLK6 in 35 brain glioma tissues and adjacent noncancerous tissues was measured using real-time quantitative polymerase chain reaction (PCR) and the relationship between KLK6 expression and pathological grades was analysed. RESULTS: The KLK6 expression in U251 cells was silenced by a specific siRNA, and the effects on proliferation, the cell cycle, and apoptosis were compared to wild type cells. Expression of KLK6 was downregulated in gliomas relative to matched noncancerous tissue. There was no obvious relationship between patient sex, pathological grade, or tumour classification and the expression of KLK6. In the U251 cell line, cell proliferation was enhanced and the fractions of cells in the G2 and S phases were increased by siRNA-mediated KLK6 silencing. CONCLUSIONS: Expression of KLK6 inhibits tumour growth. Decreased KLK6 expression may be a possible risk factor for glioma.

Hepatitis C virus infection and the risk of Sjögren or sicca syndrome: a meta-analysis.

Previous studies have suggested an association between hepatitis C virus (HCV) infection and the development of Sjögren's syndrome (SS), also known as sicca syndrome. The main objective of this study was to summarize the existing evidence and quantitatively evaluate the association between hepatitis C virus infection and SS/sicca syndrome by performing a meta-analysis of observational studies. MEDLINE and PubMed (January 1980-August 2013) were searched to identify relevant studies in English. Outcomes were calculated and are reported as odds risk (OR) and 95% CIs based on a random-effects model. Heterogeneity was assessed with I(2) statistics. Quality assessment was performed with the Newcastle-Ottawa scale. Based on meta-analysis of five cross-sectional and five cohort studies, a significant positive relationship between HCV infection and development of SS/sicca syndrome was found, the pooled random effects OR being 3.31 (95% CI, 1.46-7.48; P < 0.001). In subset analyses, the studies that used European diagnostic criteria showed a higher summary OR than did studies that adopted other diagnostic criteria. When the data were stratified by source of controls, significant associations were also observed when healthy people (OR = 9.44; 95% CI = 2.67-33.40; P = 0.204) or subjects with hepatitis B virus infection (OR = 6.57; 95% CI = 1.21-35.57; P = 0.5) were used as controls, but not when the controls were hospital-based (OR = 0.99; 95% CI = 0.61-1.61; P = 0.169). In summary, the findings suggest that HCV infection is associated with SS/sicca syndrome. The observed increased risk in studies in which European diagnostic criteria and healthy controls were used and the decreased risk in studies with hospital-based controls may be attributable to selection bias or other unknown factors.

Serum peptide pattern that differentially diagnoses hepatitis B virus-related hepatocellular carcinoma from liver cirrhosis.

BACKGROUND: Although alpha-fetoprotein (AFP) is a useful serologic marker of hepatocellular carcinoma (HCC), it is not sufficiently sensitive to differentiate HCC and liver cirrhosis (LC) caused by hepatitis B virus (HBV) infection. AIMS: The aim is to discover novel noninvasive specific serum biomarkers for the differential diagnosis of HBV-related HCC and LC. METHODS: With a highly optimized peptide extraction and matrix-assisted laser desorption/ionization time of flight/time of flight mass spectrometric approach, we investigated serum peptide profiles of 80 HCC and 67 LC patients. Three supervised machine learning methods were employed to construct classifiers. Receiver operator curves were plotted to evaluate the performance of classifiers. RESULTS: With a support vector machine-based strategy, we picked nine peaks with m/z ratios of 819.49, 1076.14, 1341.72, 2551.44, 3156.44, 3812.88, 4184.26, 4465.92, and 4776.41 to construct the classifier. We proposed a novel method for distinguishing HCC from cirrhosis, based on a multilayer perceptron (MLP) method. We obtained a sensitivity of 90.0%, specificity of 79.4%, and overall accuracy of 85.1% on an independent test set. The combination of the MLP model and serum AFP level outperformed serum AFP marker alone in distinguishing HCC patients from LC patients. In this experience, sensitivity increased from 62.5% to 87.5%, and specificity increased from 79.4% to 88.2%. CONCLUSIONS: Our results indicate that the MLP model is a novel and useful serum peptide pattern for distinguishing HCC and LC. The peptidome signature alone or together with serum AFP determination may be a more effective method for early diagnosis of HCC in patients with HBV-related LC.

Diagnostic accuracy of osteopontin for malignant pleural mesothelioma: a systematic review and meta-analysis.

BACKGROUND: Osteopontin has been viewed as a promising biomarker for malignant pleural mesothelioma (MPM); however, the conclusions of various studies on diagnostic accuracy of osteopontin have not been consistent. The aim of this study was to conduct a systematic review and meta-analysis to evaluate the diagnostic accuracy of circulating osteopontin for MPM. METHODS: Using appropriate key words, scientific literature that evaluated circulating levels of osteopontin for the diagnosis of MPM was retrieved from electronic databases. Only articles published in English till March 26, 2013 were included in this study. The quality of the studies was assessed using the revised Quality Assessment for Studies of Diagnostic Accuracy (QUADAS-2) tools. The random-effects models were applied for analysing the performance of pooled characteristics. RESULTS: Six studies were included in the analysis. The overall diagnostic sensitivity and specificity were 0.65 (95% CI: 0.60-0.70) and 0.81 (95% CI: 0.78-0.85), respectively. The area under summary receiver operating characteristic (sROC) curves (AUC) was 0.83. The diagnostic accuracy of serum and plasma osteopontin was comparable. CONCLUSIONS: Osteopontin is an effective marker for MPM diagnosis. However, more studies with a larger sample size and better design are needed to rigorously assess the diagnostic power of osteopontin.