OBJECTIVETo study the clinical significance of hepatitis B surface antigen (HBsAg) levels and HBsAg/hepatitis B virus (HBV) DNA ratio in relation to liver inflammation in HBeAg-positive chronic hepatitis B (CHB).

METHODSOne hundred and fifty-three Chinese patients with chronic HBV infection with HBeAg-positive status were enrolled in the study.Quantitative measurements were made for HBsAg levels by immunoassay (Architect HBsAg QT by Abbott Diagnostic) and HBV DNA by real-time fluorescence quantitative PCR.Levels of liver function markers were measured by standard methods.Liver biopsy specimens were obtained from all patients and used to score the histology (liver inflammation) activity index (HAI) and grade (G) the extent of necroinflammation.Statistical correlation analysis was performed to determine the association of HBsAg titre or HBsAg/HBV DNA ratio with the various parameters of liver injury.

RESULTSHBsAg titre and HBsAg/HBV DNA ratio were significantly correlated (r =0.578, P less than 0.0001).A significant positive correlation (r =0.642, P less than 0.0001) was found between HBsAg titre and HBV DNA load, and a significant negative correlation was found between the HAI and HBsAg (r =-0.389, P less than 0.0001) and HBsAg/HBV DNA ratio (r =-0.307, P=0.000l).A significant positive correlation was found between alanine aminotransferase (ALT) level and the HAI (r =0.480, P less than 0.0001).Patients with G less than 2 necroinflammation had significantly higher HBsAg titre and HBsAg/HBV DNA ratio than patients with G more than or equal to 2 necroinflammation (both P less than 0.01) but similar levels ofHBV DNA.Generation of a receiver operating characteristic curve using G more than or equal to 2 as the positive index provided the following area under the curve (AUC) values:HBsAg titre, 0.700; HBsAg/HBV DNA ratio, 0.672; ALT level, 0.713.When the random chance AUC was 0.5, all levels of AUC were statistically significant (Pless than 0.001).HBsAg titre (sensitivity =76.92%) was more sensitive than ALT level (sensitivity =76.92%), and HBsAg/HBV DNA ratio (specificity =81.33%) was more specific than ALT level (specificity =81.33%).Youden's index for comprehensive evaluation using ALT was higher than those for HBsAg titre or HBsAg/HBV DNA ratio.When HBsAg and ALT were considered in parallel, the sensitivity increased to 94.08% and specificity rose to 85.60%.

CONCLUSIONHBsAg titre, HBsAg/HBV DNA ratio and ALT levels can be used as the index for judging the degree of liver inflammation in HBeAg-positive CHB patients.Higher sensitivity and specificity are attained when HBsAg and ALT are used in series or parallel.

Alanine Transaminase ; Area Under Curve ; Biomarkers ; DNA, Viral ; Hepatitis B e Antigens ; Hepatitis B virus ; Hepatitis B, Chronic ; Humans ; Inflammation ; ROC Curve ; Real-Time Polymerase Chain Reaction ; Serologic Tests

Objective:To construct a clinical-radiomics model based on MRI, and to explore its predictive value for biochemical recurrence (BCR) after radical prostatectomy in prostate cancer patients.Methods:A total of 212 patients with prostate cancer who underwent radical prostatectomy in the First Affiliated Hospital of Soochow University from January 2015 to December 2018 and had complete follow-up data were retrospectively analyzed. The random toolkit of Python language was used to randomly sample the patients at a ratio of 7∶3 without replacement, and they were divided into a training set (149 cases) and a test set (63 cases). The endpoint of follow-up was BCR or at least 3 years. BCR occurred in 50 patients in the training group and 21 patients in the test group. The imaging features of the main lesion area in the preoperative T 2WI, diffusion-weighted imaging and apparent diffusion coefficient map of patients in the training set were extracted, and the unsupervised K means clustering algorithm was used to screen the features. The selected features were fitted by a multivariate Cox regression model, and the radiomics model was constructed. Univariate Cox regression analyses were used to screen the main clinical risk factors associated with BCR, and the clinical-radiomics model was constructed combined with RadScore. In the test set, the time-dependent receiver operating characteristic (ROC) curve was constructed, and the area under the curve (AUC) was calculated to evaluate the predictive efficacy of the radiomics model, clinical-radiomics model and prostate cancer risk assessment after radical resection (CAPRA-S) score for the occurrence of BCR. Harrell consistency index (C-index) was used to evaluate the model to predict BCR consistency. The calibration curve was used to evaluate the degree of variation of the model. The decision curve was used to evaluate the clinical application value of the prediction model. Results:A total of 26 radiomics features were screened to establish the radiomics model. The univariate Cox showed that the preoperative clinical features included preoperative prostate-specific antigen level (HR=1.006, 95%CI 1.002-1.009, P=0.001), Gleason score of biopsy (HR=1.422, 95%CI 1.153-1.753, P=0.001), clinical T stage (HR=1.501, 95%CI 1.238-1.822, P<0.001). The multivariate Cox showed that the RadScore was an independent predictor of BCR after radical prostatectomy (HR=51.214, 95%CI 18.226-143.908, P<0.001). The selected preoperative clinical features were combined with RadScore to construct a clinical-radiomics model. In the test set, the AUCs of the time (3 years)-dependent ROC curves of the radiomics model, the clinical-radiomics model, and the CAPRA-S score were 0.824 (95%CI 0.701-0.948), 0.841 (95%CI 0.714-0.968), and 0.662 (95%CI 0.518-0.806), respectively. The C-index of the radiomics model, clinical-radiomics model and CAPRA-S score were 0.784 (95%CI 0.660-0.891), 0.802 (95%CI 0.637-0.912) and 0.650 (95%CI 0.601-0.821), respectively. The calibration curve showed that the predicted probability and actual probability of BCR by radiomics model, clinical-radiomics model and CAPRA-S score were in good agreement (χ 2=7.64, 10.61, 6.37, P=0.465, 0.225, 0.498). The decision curve showed that the clinical net benefit of the clinical-radiomics model and the radiomics model was significantly higher than the CAPRA-S score. When the threshold probability was 0.20-0.30, 0.40-0.50, and >0.55, the clinical net benefit of the clinical radiomics model was higher than that of the radiomics model. Conclusions:The clinical-radiomics model can effectively predict the occurrence of BCR in patients with prostate cancer after radical prostate ctomy, and the prediction efficacy is better than the radiomics model and CAPRA-S score.

The Ly-6 and uPAR (LU) domain-containing proteins represent a large family of cell-surface markers. In particular, mouse Ly-6A/Sca-1 is a widely used marker for various stem cells; however, its human ortholog is missing. In this study, based on a systematic survey and comparative genomic study of mouse and human LU domain-containing proteins, we identified a previously unannotated human gene encoding the candidate ortholog of mouse Ly-6A/Sca-1. This gene, hereby named LY6A, reversely overlaps with a lncRNA gene in the majority of exonic sequences. We found that LY6A is aberrantly expressed in pituitary tumors, but not in normal pituitary tissues, and may contribute to tumorigenesis. Similar to mouse Ly-6A/Sca-1, human LY6A is also upregulated by interferon, suggesting a conserved transcriptional regulatory mechanism between humans and mice. We cloned the full-length LY6A cDNA, whose encoded protein sequence, domain architecture, and exon-intron structures are all well conserved with mouse Ly-6A/Sca-1. Ectopic expression of the LY6A protein in cells demonstrates that it acts the same as mouse Ly-6A/Sca-1 in their processing and glycosylphosphatidylinositol anchoring to the cell membrane. Collectively, these studies unveil a novel human gene encoding a candidate biomarker and provide an interesting model gene for studying gene regulatory and evolutionary mechanisms.
Humans ; Membrane Proteins/genetics* ; Pituitary Neoplasms/genetics* ; Biomarkers