Host response biomarkers can accurately distinguish between influenza and bacterial infection. However, published biomarkers require the measurement of many genes, thereby making it difficult to implement them in clinical practice. This study aims to identify a single-gene biomarker with a high diagnostic accuracy equivalent to multi-gene biomarkers.In this study, we combined an integrated genomic analysis of 1071 individuals with experiments using well-established infection models.We identified a single-gene biomarker,, which had a high prediction accuracy (91%) equivalent to that obtained by multi-gene biomarkers. studies showed that was upregulated by TLR7 in plasmacytoid dendritic cells, antigen-presenting cells that responded to influenza virus rather than bacteria. studies confirmed that was expressed in influenza patients but not in bacterial infection, as demonstrated in multiple patient cohorts (n=521). In a large prospective study (n=439) of patients presented with undifferentiated respiratory illness (aetiologies included viral, bacterial and non-infectious conditions), displayed 88% diagnostic accuracy (AUC) and 90% specificity in discriminating between influenza and bacterial infections. represents a significant step forward in overcoming a translational barrier in applying genomic assay in clinical setting; its implementation may improve the diagnosis and management of respiratory infection.

We examined whether the hepatitis B virus (HBV) pregenomic RNA (pgRNA) status after nucleos(t)ide (NA) treatment can predict the long‐time prognoses of chronic hepatitis B patients. Patients with chronic hepatitis B (98) who were treatment‐naïve and had begun a 7‐year NA therapy regimen were enrolled in this study. Biochemical indicators and serological markers of HBV infection were performed during therapy. HBV pgRNA was quantified by real‐time quantitative PCR with specific primers. During treatment, HBV DNA undetectable rates increased. The aminotransferase (ALT) normalization (ALT < 50 IU/L) and HBeAg‐negative rates also increased. After 48 weeks’ NA treatment, 48.28% (28/58) of HBV DNA undetectable patients still had HBV pgRNA‐positive. After 7 years of treatment, more HBV pgRNA‐negative patients (n = 35) achieved HBeAg clearance than the patients who were HBV pgRNA‐positive (n = 63) (19/23 vs 19/56, P < .00). HBV pgRNA‐positive patients also had an increased risk of failing to achieve HBeAg clearance (OR = 9.25, 95% CI: 2.75‐31.08). The median time to HBeAg clearance in the HBV pgRNA‐positive patients was longer than that of the HBV pgRNA‐negative patients (152 weeks vs 72 weeks). The HBV pgRNA‐positive patients also required more time to achieve HBV DNA undetectable (124 weeks, 95% CI: 103.33‐144.67 vs 48 weeks, 95% CI: 34.80‐61.20). The HBV pgRNA status after NA treatment can predict the long‐term prognoses of patients with chronic HBV. Patients who remain HBV pgRNA‐positive after 48 weeks of NA treatment have an increased risk of not achieving HBeAg clearance, need more time to achieve HBeAg clearance and undetectable HBV DNA load.

BACKGROUNDCharacteristics of alterations of serum hepatitis B virus (HBV) RNA in different chronic hepatitis B (CHB) patients still cannot be fully explained. Whether HBV RNA can predict HBeAg seroconversion is still controversial.AIMTo investigate whether HBV RNA can predict virological response or HBeAg seroconversion during entecavir (ETV) treatment when HBV DNA is undetectable.METHODSThe present study evaluated 61 individuals who were diagnosed and treated with long-term ETV monotherapy at the Department of Infectious Diseases of Peking University First Hospital (China) from September 2006 to December 2007. Finally, 30 treatment-naive individuals were included. Serum HBV RNA were extracted from 140 μL serum samples at two time points. Then they were reverse transcribed to cDNA with the HBV-specific primer. The product was quantified by real-time quantitative PCR (RT-PCR) using TAMARA probes. Statistical analyses were performed with IBM SPSS 20.0.RESULTSLevel of serum HBV RNA at baseline was 4.15 ± 0.90 log10 copies/mL. HBV RNA levels showed no significant difference between the virological response (VR) and partial VR (PVR) groups at baseline (P = 0.940). Serum HBV RNA significantly decreased among patients who achieved a VR during ETV therapy (P < 0.001). The levels of HBV RNA in both HBeAg-positive patients with seroconversion group and those with no seroconversion increased after 24 wk of treatment. Overall, HBV RNA significantly but mildly correlated to HBsAg (r = 0.265, P = 0.041), and HBV RNA was not correlated to HBV DNA (r = 0.242, P = 0.062). Furthermore, serum HBV RNA was an independent indicator for predicting HBeAg seroconversion and virological response. HBeAg seroconversion was more likely in CHB patients with HBV RNA levels below 4.12 log10 copies/mL before treatment.CONLUSIONThe level of serum HBV RNA could predict HBeAg seroconversion and PVR during treatment. In the PVR group, the level of serum HBV RNA tends to be increasing.

BackgroundReactivation of hepatitis B virus (HBV) is a fatal complication of chemotherapy. Occult HBV infection might be reactivated in patients undergoing chemotherapy or immunosuppression. However, the mechanism of HBV reactivation induced by chemotherapy or immunosuppression remains unclear.Material/MethodsHepG2.2.15 cells were treated with an autophagy inducer (rapamycin), an inhibitor (3-methyladenine, 3-MA), and dexamethasone. Autophagosomes were observed by a transmission electron microscope (TEM). LC3-I, LC3-II, and P62 were analyzed by western blot. HBV replicative intermediates were detected by southern blot. HBV DNA expression was quantitated with real-time polymerase chain reaction (PCR). The level of HBV surface antigen (HBsAg) in culture medium was examined by ELISA.ResultsIn this study, we find that dexamethasone stimulates HBV replication and protein expression by inducing autophagy in HepG2.2.15 cells. In contrast, autophagy inhibitor (3-MA) abrogates HBsAg secretion stimulated by dexamethasone.ConclusionsOur results suggest that dexamethasone stimulates HBV replication through autophagy. This might provide a novel insight into the mechanism of glucocorticoid-mediated HBV reactivation through autophagy, which might be a new therapeutic target.