Background: Although alanine aminotransferase (ALT) is well known to be associated with metabolic syndrome (MetS), prospective data on longitudinal increments in ALT activities and incident cases of MetS are limited. We analyzed the impact of longitudinal increments of ALT on MetS based on a health check-up population in China. Methods: A total of 4491 subjects free of MetS who completed at least two annual health examinations during March 2010 to April 2016 were enrolled in this cohort study. The MetS was defined according to the Joint Interim Statement criteria 2009. The RRs of incident MetS were estimated by using the Cox model and the Joint model in R software. Results: The cumulative incidence of MetS was 18.55% during the 7 years of follow-up. In the Cox model, the estimated RR of developing MetS was 1.751 (95% CI =1.532-2.000) for 1 unit augmented in LNALT-0 level. In the Joint model, the estimated RR of developing MetS was 3.626 (95% CI = 2.721-4.831) for 1 unit augmented in LNALT activity longitudinally. Conclusions: The longitudinal increment of individuals' ALT activity over time increased the incidence risk of MetS and the effects generated by longitudinal increments of ALT on MetS was higher than that generated by baseline ALT.
Dickkopf-1 (Dkkl)'s dysregulation has been implicated in the pathogenesis of a variety of cancers. It is part of the Dkk family of proteins that includes Dkk2, Dkk3 and Dkk4. This family of secreted proteins shares similar conserved cysteine domains and inhibits the Wnt/b-catenin pathway by causing proteasomal B-catenin degradation, inducing apoptosis, and preventing cell proliferation. Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer mortality in the United States due to the late stage of diagnosis and the limited effectiveness of current therapy. Dkkl is found increased in PADC patients' specimens and serum. Dkkl can be a promising biomarker specific to PDAC, which has the potential to increase PDAC survival rates through improving early stage detection and monitoring progression compared to current biomarker gold standards. In addition, recent studies suggest that Dkkl could be an excellent target for cancer immunotherapy. Interestingly, Dkkl-CKAP4-PI3K/AKT signal pathway also plays role in pancreatic cancer cell proliferation. In this review, we present the multiple mechanisms of Dkkl in PDAC studied thus far and explore its function, regulation, and clinical applications in gynecological cancers including pancreatic ductal adenocarcinoma (PDAC), breast, ovarian, cervical, and endometrial cancer. Further research into Dkkl's mechanism and use as a diagnostic tool, alone or in combination with other biomarkers, could prove clinically useful for better understanding the pathology of PDAC and improving its early detection and treatment.
Background Endometrial cancer (EC) is common type of gynecologic malignancy affecting a large number of females around the world. While most early stage cases are well managed with a relatively benign prognosis, the late stage cases have poor survival. Among the many biomarkers identified, serum human epididymis protein 4 (HE4) and CA125 are most promising surrogates for EC detection. Methods: We performed a meta-analysis to estimate the diagnostic accuracy of HE4 and CA125 and compared their performance. A literature research was performed in Medline, Cochrane Literature Library and CNKI. After filtering, twelve studies evaluating the diagnostic value of serum HE4, alone or in comparison with CA125, were included. The total sample size was 1106 patients and 1480 controls. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) were calculated and summary receiver operating characteristic (SROC) curves were plotted to assess the diagnostic accuracy. Results: The pooled estimates for HE4 were sensitivity: 0.71 (95%Cl 0.56-0.82), specificity: 0.87 (95%Cl 0.80-0.92), and area under ROC curve: 0.88 (0.85-0.91), compared to 0.35 (95% CI 0.25-0.46), 0.83 (95% CI 0.71-0.91), and 0.58 (95% CI 0.54-0.63), respectively, of CA125. Subgroup analysis demonstrated a better performance of HE4 in Caucasian population, compared to Chinese population. Conclusion: This analysis suggested that when stage and histological type are not specifically considered, serum HE4 is generally a better tool than CA125 in EC diagnosis by its significantly higher sensitivity than CA125.
Background. Development of a test card based on up-conversion phosphor technology-based immune lateral flow (UPT-LF) assay as a near-patient detection tool for serum Prothrombin induced by vitamin K absence or antagonist II (PIVKA-II). Methods: Up-converted phosphor nanoparticles (UCPs) were used to bind to PIVKA-II monoclonal antibodies as labeled probes to develop the test card for detecting serum PIVKA-II. The UPT-LF test card was evaluated by the limit of detection, linearity, stability, recovery rate, precision and interference. Preliminary clinical validation was conducted by detection of 498 serum samples from 228 patients with hepatocellular carcinoma (HCC), 170 patients with liver benign lesion (LBL) and 100 healthy controls (HC). Additionally, the correlation of serum PIVKA-II detection between UPT-LF assay and Chemiluminescence enzyme immunoassay (CLEIA) assay were performed. Results: Modified and activated UCPs bound to monoclonal antibodies powerfully to form the luminescent labeled probes. Limit of detection and linear range of UPT-LF test card for serum PIVKA-II were 2.66 and 4.8-20,000 ng/ml, respectively. Test card had good 25 degrees C thermal and 4 degrees C validity period stability, 93.1%-99.2% of recovery rate, 2.6-5.8% and 5.4-8.9% of intra-assay and inter-assay CVs, and strong anti interference ability for 8 common serum analytes. The sensitivity and specificity (vs LBL + HC group) of test card for HCC were 71.5% and 88.9%, respectively. The R2 between UPT-LF assay and CLEIA assay was 0.901. Conclusions: UPT-LF assay provides a reliable, rapid and convenient test for quantitative detection of serum PIVKA-II as well as diagnosis of HCC by a point of care testing way.
Background: Pannexin-1 is a type of hexameric plasma membrane channel-forming proteins, and plays a significant role in brain injury. We investigated the potential prognostic value of pannexin-1 in traumatic brain injury. Methods: A single peripheral blood sample in 112 patients with severe traumatic brain injury and 112 controls was prospectively collected for subsequent measurement of serum pannexin-1. Clinical follow-up was performed at 6 months. An unfavorable outcome was defined as Glasgow Outcome Scale score of 1-3. Results: The patients showed markedly higher serum pannexin-1 concentrations than the controls. Among the patients, pannexin-1 concentrations were significantly and negatively correlated with Glasgow coma scale scores. On receiver operating characteristic curve analysis, the predictive value in terms of area under the curve was substantially high for serum pannexin-1 as a predictor for both 6-month mortality and unfavorable outcome. Regression analyses confirmed that there was an increased risk of either 6-month mortality, overall survival or unfavorable outcome associated with serum pannexin-1 concentrations after adjusting for possible confounders. Conclusions: Serum pannexin-1 may represent a potential prognostic biomarker for head trauma.
Background: Recent studies have borne out claims that inflammation has a vital role in the development and progression of many diseases, including cancers. It has been reported that neutrophil-lymphocyte ratio (NLR) and red blood cell distribution width (RDW) could act as independent prognostic factors for several malignant tumors. We evaluated the diagnosis and prognosis values of preoperative inflammatory indicators, including NLR and RDW in esophageal cancer (EC). Methods: We retrospectively analyzed the clinical data of 354 EC patients and 220 early esophageal cancer (EEC) undergoing potentially curative esophagectomy in Shandong Provincial Hospital Affiliated to Shandong University and chose 201 age and sex-matched healthy volunteers as the control group. We compared the clinicopathological features, survival curves and prognosis of the EC patients between the high and low groups according to the cutoff values of NLR and RDW. Results: Significant higher preoperative NLR and RDW values were detected in patients with EEC and EC compared to the healthy controls (P <.001). A high RDW was significantly associated with an older age (P <.05). NLR and RDW values after surgery in EC group were significantly higher than those before surgery (P <.001 and P <.001, respectively). For EEC group, a higher RDW value showed a significantly worse overall survival (OS) and disease-free survival (DFS) (P =.040 and P =.013, respectively). For EC group, an increased NLR indicated a significantly association with poor overall survival (OS) (P =.004) and DFS (P =.001). Preoperative NLR can act as an independent prognostic indicator for EC. Conclusion: The preoperative NLR and RDW are convenient, practical easily measured biomarkers of clinical diagnosis and prognostic assessment of patients with EC. Furthermore, NLR was more effective than RDW acting as an independent prognostic biomarker for EC.
Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a novel inflammatory biomarker, which is useful as an adjunct identification tool for cardiovascular disease. However, the important limitation of the conventional enzyme-linked immunosorbent assay (PLAC ELISA) for Lp-PLA2 assay is its relatively low sensitivity and time consuming. A method to measure the Lp-PLA2 simply, rapidly and sensitively is essential for predicting cardiovascular events in clinic. Methods: We took advantage of magnetic separation integrated with chemiluminescence to detect Lp-PLA2. The concentration of Lp-PLA2 was measured through a one-step process by mixing antibody labelled magnetic beads, antigen and antibody at one time. Results: Our method realized the sample to answer within 17 min. The detection limit and measurement range were 0.18 ng/ml and 0.18-1350 ng/ml, respectively. The specificity assay showed that no appreciable interference was observed for the substances of bilirubin, triglyceride, hemoglobin, rheumatoid factor and human anti-mouse antibody up to the concentrations of 40 mg/dl, 1000 mg/dl, 2000 mg/dl, 1500 IU/ml and 30 ng/ml, separately. We also tested 122 clinical samples using our method, presenting good overall correlations (R2 = 0.979) to the PLAC ELISA. It is worth mentioning that, our method was faster, had a wider range of measurement and higher sensitivity compared with the PLAC ELISA. Conclusions: The Lp-PLA2 assay is straightforward, sensitive and precise, which is highly suitable to further explore the clinical performance of Lp-PLA2 in studies of cardiovascular risk management.
LncRNAs are a group of noncoding RNAs that are > 200 nucleotides in length. These RNAs have no significant protein-coding potential due to the lack of obvious open reading frames. To date, accumulating evidence has demonstrated that dysregulation of lncRNAs exhibits indispensable roles in the pathological processes of human cancers. These RNAs function as either oncogenes or tumor suppressor genes to regulate proliferation, migration and invasion of cancer cells. GHET1, a prominent oncogenic lncRNA, is highly expressed in diverse malignancies. Furthermore, GHET1 performs key functions in carcinogenesis and progression, suggesting that GHET1 is expected to be a prospective biomarker or therapeutic target for cancers. In this review, we provide a summary of the current evidence concerning the biological functions, underlying mechanisms and clinical significance of GHET1 during tumor development.
Objective: The study was designed to analyze three different algorithms with the implementation of treponema tests for detecting suspected syphilis in west China where no syphilis algorithms guideline exists. Methods: We retrospectively collected data to reanalyze three syphilis testing algorithms: the classical revers algorithm, and two options of syphilis screening in European syphilis guideline. The kappa (kappa) coefficients were used to compare the concordance between algorithms using different syphilis assays during two periods. I receiver operating characteristic curve was used to determine the optimal S/CO ratios of InTec EIA o Lumipulse (R) G TP-N assay (CLIA) to predict confirmatory TPPA results. Results: The agreements between the reverse algorithm and the EU option 1 algorithms were perfect irrespective of EIA or CLIA used (all kappa > 0.9). But the agreements between the EU option 2 algorithms and reverse or Et option 1 were not good (kappa < 0.4). > 50% cases confirmed syphilis infections by reverse or EU option 1 algo rithm were missed by EU option 2. There is no very need for a confirmatory TPPA assay in EU Option 1 when S, CO is above 6.12 for CLIA (3.67 for EIA). The false-positive rate was 0.26% above this cutoff level. Conclusions: EU Option 1, involving a reactive TT, followed by another Tr of a different type and a quantitative NTT if second TT is positive, which is the same as the 2015 UK syphilis algorithm, is recommended. We also propose that when S/CO of the CLIA or EIA is high enough, TPPA confirmation can be omitted from the testing algorithm, and costs would be significantly reduced.
Background and aims: Metabolomics serves as an important tool in distinguishing changes in metabolic pathway and the diagnosis of human disease. Hepatocellular carcinoma (HCC) is a malignance present of heterogeneous metabolic disorder and lack of effective biomarker for surveillance and diagnosis. In this study, we searched for potential metabolite biomarkers of HCC using tissue and serum metabolomics approach. Methods: A total of 30 pairs of matched liver tissue samples from HCC patients and 90 serum samples (30 HCC patients, 30 liver cirrhosis patients, and 30 healthy individuals) were assessed. Metabolomics was performer through ultra performance liquid chromatography-mass spectrometry in conjunction with multivariate and univariate statistical analyses. Results: A total of six differential metabolites including chenodeoxycholic acid (CDCA), glycocholic acid (GCA) LPC20:5, LPE18:0, succinyladenosine and uridine were present in HCC tissue and serum samples. CDCA LPC20:5, succinyladenosine and uridine were used to construct a diagnostic model based on logistic regression The four-metabolite panel discriminated HCC from liver cirrhosis with an AUC score of 0.938, sensitivity of 93.3% and specificity of 86.7%. For all HCC and cirrhosis patients, the diagnostic accuracy increased to 96.7% and 90.0%, respectively. Conclusion: The combination of CDCA, LPC20:5, succinyladenosine and uridine can be used as a biomarker panel to improve HCC sensitivity and specificity. This panel significantly benefits HCC diagnostics and reveal new insight into HCC pathogenesis.
Background: Translocator protein (TP) is related to inflammation and is involved in brain injury. The objective of this study was to ascertain whether serum TP concentrations are associated with the severity and prognosis of traumatic brain injury (TBI). Methods: We quantified the serum concentrations of TP in 106 healthy controls and 106 patients with severe TBI. Recorded prognostic variables included acute lung injury, acute traumatic coagulopathy, progressive hemorrhagic injury, posttraumatic cerebral infarction, 6-month mortality and 6-month poor outcome (Glasgow Outcome Scale score of 1-3). Trauma severity was assessed by Glasgow coma scale (GCS) score. Extent of inflammatory response was indicated by serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-a) and C-reactive protein (CRP) concentrations. Results: Patients had significantly higher serum TP concentrations than controls. Among patients, serum TP concentrations strongly and independently correlated with GCS score and serum IL-6, TNF-a and CRP concentrations. Serum TP was identified as an independent predictor for the preceding prognostic variables, its prognostic predictive ability was similar to that of GCS score and it also significantly improved prognostic predictive ability of GCS score. Conclusion: Serum TP may be intimately linked with in inflammation, disease progression and poor prognosis in TBI patients.
Background: Previous studies in animal model have demonstrated that neurotrophins were associated with functional outcome following stroke. However, the relationship between serum nerve growth factor (NGF) and functional outcome in stroke patients has not been explored. Our objective was to investigate the association between serum NGF concentrations at admission and functional outcome of patients at 3 month after stroke. Methods: One-hundred eight-five patients with acute ischaemic stroke were recruited in our study. Serum NGF concentrations were measured by ELISA at admission. The stroke severity at admission was assessed by the National Institute of Health Stroke Scale (NIHSS). The modified Rankin Scale (mRS) was used to assess the functional outcome of patients at 3 month after stroke. In addition, 100 healthy controls were recruited. Results: Serum NGF concentrations were higher in good functional outcome group (mRS score of 0-2) than that in poor functional outcome group (mRS score of 3-6) (9.51 +/- 2.33 vs. 8.12 +/- 1.61, P < 0.001). Meanwhile the serum NGF concentrations in healthy group were lower than that in acute ischemic stroke patient (7.17 +/- 1.49 vs. 9.15 +/- 2.24, P < 0.001). Moreover, our results demonstrated that high serum NGF con centrations (> 9.21 ng/l) were independently associated with the better functional prognosis at 3 months following the occurrence of stroke (OR 0.048, 95% CI 0.012-0.185, P < 0.001). Conclusions: High concentrations of serum NGF at admission may predict good functional outcome of patients a 3 months after acute cerebral ischemia stroke.
Objective: The objective of this study was to screen new antigens for syphilis serodiagnosis. Methods: First, we determined whether the Treponema pallidum proteins Tp0971, Tp0768 and Tp0462 were infection phase-dependent antigens by observing serum reactivity differences in New Zealand rabbits infected with activated or inactivated T. pallidum. A non-infection phase-dependent antigen, the Tp92 membrane protein, was used as the negative control. Next, Tp0971-, Tp0768- and Tp0462-based ELISA was performed on 2138 human serum samples and compared with the T. pallidum passive particle agglutination assay (TPPA) and LiZhu (TM) Tp-ELISA. In addition, another 60 paired serum samples from patients at follow-up were analysed to evaluate the relationships between titre changes and differences in the A450 nm values of the Tp0971, Tp0768, Tp0462 and Tp92 antibodies measured by ELISA. Results: Compared with Tp92 (negative control), Tp0971, Tp0768 and Tp0462 were determined to be infection phase-dependent antigens. Compared with those of the TPPA, the sensitivities of Tp0971-, Tp0768- and Tp0462-based ELISA were 96.4%, 96.9% and 93.0%, respectively, and the specificities were 97.7%, 95.4% and 98.9%, respectively, resulting in consistencies of 97.1%, 96.2% and 95.9%, respectively. Compared with those of the LiZhu (TM) Tp-ELISA, the consistencies of Tp0971-, Tp0768- and Tp0462-based ELISA were 95.1%, 94.2% and 94.0%, respectively, with kappa values of 0.902, 0.884 and 0.880, respectively. Tp0971, Tp0768 and Tp0462 demonstrated high sensitivities and specificities, as well as high conformity to the TPPA and LiZhu (TM) Tp-ELISA. Moreover, a significantly positive Spearman rank correlation coefficient (0.82,*P < 0.05) was found between the difference in the A450 nm values of the Tp0971 antibody and the RPR titre change. Conclusion: The infection phase-dependent antigens Tp0971, Tp0768 and Tp0462 are promising for syphilis diagnosis, and Tp0971 may be utilized to monitor curative effects during syphilis treatment.
RAS oncogene mutations frequently occur in acute myeloid leukaemia (AML), but the prognostic significance of RAS mutations in AML is inconclusive. We searched the databases of PubMed, Web of Science, EMBASE, and Cochrane from 1990 to 2018. In this study, 24 eligible studies were included, and the meta-analysis was conducted with the Comprehensive Meta-Analysis Version 2 software program. The row hazard ratio (HR) was adjusted and re-evaluated when publication bias existed after detecting all the heterogeneities. A combined analysis showed that RAS mutations were not associated with a poor prognosis in general AML patients (HR: 0.96, 95% CI: 0.78-1.19, p = 0.70). To further verify the results, a subgroup analysis was conducted. Interestingly, in the analysis of age bracket, children with RAS mutations had an unfavourable survival (HR: 1.35, 95% CI: 1.05-1.75, p = 0.02) of AML, but the adults did not (HR: 0.87, 95% CI: 0.70-1.09, p = 0.21). Further analysis of the subgroup of children indicated that patients with NRAS mutations had an adverse prognosis (FIR: 1.55, 95% CI: 1.13-2.12, p = 0.007), but not those with KRAS mutations (HR: 1.51, 95% CI: 0.34-6.73, p = 0.59). In conclusion, this study revealed that RAS mutations did not influence the over survival for adults with AML. However, NRAS mutations may be a key prognostic marker related with poor survival for children with AML.