Qing Mao

Objective: Hepatitis B surface antigen (HBsAg) clearance is a key milestone for functional (clinical) cure of chronic hepatitis B virus (HBV) infection. However, data on the efficacy and safety of pegylated interferon alpha (Peg-IFNα) for HBsAg clearance in postpartum women with chronic HBV infection remain scarce. This study aimed to prospectively evaluate the efficacy and safety of Peg-IFNα in promoting HBsAg clearance in this specific population. Methods: A total of 263 HBV-infected postpartum women with a baseline HBsAg levels ≤3000 IU/mL were enrolled. Based on patient preference, they were assigned to either the Peg-IFNα group (n=62, receiving Peg-IFNα monotherapy or combination therapy with nucleos(t)ide analogs [NAs]) or the control group (n=201, receiving NAs or follow-up only). The duration of Peg-IFNα treatment was ≥48 weeks. Propensity score matching (PSM) was performed to balance baseline characteristics. The primary endpoints were both HBsAg clearance rate and the magnitude of HBsAg decline. Results: At week 48, the Peg-IFNα group had significantly higher HBsAg clearance (29.03% [18/62]) and seroconversion rates (27.42% [17/62]) than the control group (both 0%, P < 0.001). Post-PSM, the Peg-IFNα group still had a significantly higher HBsAg clearance/seroconversion rate (30.43% [14/46]) versus the control group (0%, P < 0.001). Subgroup analysis showed that patients with baseline HBsAg < 1000 IU/mL had higher clearance rates (pre-PSM: 39.02% [16/41]; post-PSM: 40.00% [12/30]). Receiver operating characteristic (ROC) curve analysis identified a ≥ 99.2% HBsAg reduction from baseline to week 12 as a strong predictor of week 48 HBsAg clearance (AUC ≥0.9; sensitivity =0.818; specificity= 1.000). Conclusion: Peg-IFNα treatment can achieve high rates of HBsAg clearance and seroconversion in postpartum women with chronic HBV infection. The postpartum period represents a unique and favorable immune window for interferon-based intervention, and patients with baseline HBsAg <1000 IU/mL derive particular benefit from this strategy.

Background: This study aims to investigate the impact of home quarantine on insulin resistance and other metabolic parameters in general populations through the changes in metabolic profile, especially Triglyceride/Glucose (TyG).Methods: This study included participants who underwent two health checkups at the Health Management Center of the First Affiliated Hospital of the Army Medical University, before and after home quarantine, between December 2021 and February 2023. The home quarantine policy in the Chongqing area was executed between August 2022 and December 2022. Triglyceride/Glucose (TyG), TyG-body mass index (TyG-BMI), and TyG-waist circumference (TyG-WC) were calculated.Results: A total of 19,957 cases were screened, and 2,473 participants (mean age: 39.35 ± 10.36 years, 69.8% female) were included for the final analysis. Compared to before home quarantine, the TyG (6.80 ± 0.58 vs. 6.83 ± 0.58, p < 0.001), TyG-BMI (158.30 ± 31.92 vs. 159.48 ± 31.73, p < 0.001), and TyG-WC (533.53 ± 103.15 vs. 535.78 ± 103.65, p = 0.039) increased significantly after the home quarantine. Besides, glucose, lymphocyte, and platelet decreased significantly while BMI, systolic blood pressure, diastolic blood pressure, pulse, total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, uric acid, red blood cell, and monocyte also increased significantly after home quarantine (all p < 0.05).Conclusion: Home quarantine might pose a potential negative impact on insulin resistance risk, indicating that insulin resistance and other metabolic health parameters during the home quarantine period should be monitored regularly.

Background Currently, pegylated interferon-α (Peg-IFN-α)-based antiviral therapy brings dawn to the clinical cure of chronic hepatitis B(CHB). Our aim was to investigate markers associated with clinical cure and off-treatment hepatitis B surface antigen (HBsAg) reversion in CHB receiving Peg-IFN-α-based therapy. Methods In total, 101 patients with hepatitis B e antigen-negative CHB who were treatment-naive or nucleotide analogs(NAs) treated patients were enrolled, then they were all received Peg-IFN-α-based therapy. Hepatitis B core-related antigen (HBcrAg), HBsAg and hepatitis B surface antibody (HBsAb) levels were examined dynamically and used to investigate the predictive value for HBsAg clearance and off-treatment reversion. Results Out of 101 patients, 41(40.59%) individuals achieved HBsAg clearance at the end of treatment (EOT). High baseline HBsAg (2.32 log₁₀ IU/mL) combined with HBcrAg (3.90 log₁₀ U/mL) was strongly associated with the HBsAg clearance (AUC = 0.714, P10 U/mL and HBsAb ≥ 51.50 IU/L at EOT had a negative predictive value of 85.71% for off-treatment HBsAg reversion (AUC = 0.840, P < 0.001). Conclusions HBcrAg and HBsAg can be used to predict clinical cure, while the HBcrAg and HBsAb were closely related to the off-treatment HBsAg reversion in patients with CHB receiving Peg-IFN-α-based therapy.

Background: T cells play critical roles in the progression of tuberculosis (TB); however, knowledge regarding these molecular mechanisms remains inadequate. This study constructed a critical ceRNA network was constructed to identify the potentially important role of TB activation via T-cell regulation.Methods: We performed integrated bioinformatics analysis in a randomly selected training set from the GSE37250 dataset. After estimating the abundance of 18 types of T cells using ImmuCellAI, critical T-cell subsets were determined by their diagnostic accuracy in distinguishing active from latent TB. We then identified the critical genes associated with T-cell subsets in TB activation through co-expression analysis and PPI network prediction. Then, the ceRNA network was constructed based on RNA complementarity detection on the DIANA-LncBase and mirDIP platform. The gene biomarkers included in the ceRNA network were lncRNA, miRNA, and targeting mRNA. We then applied an elastic net regression model to develop a diagnostic classifier to assess the significance of the gene biomarkers in clinical applications. Internal and external validations were performed to assess the repeatability and generalizability.Results: We identified CD4⁺ T, Tr1, nTreg, iTreg, and Tfh as T cells critical for TB activation. A ceRNA network mediated by the MIR600HG/hsa-mir-21-5p axis was constructed, in which the significant gene cluster regulated the critical T subsets in TB activation. MIR600HG, hsa-mir-21-5p, and five targeting mRNAs (BCL11B, ETS1, EPHA4, KLF12, and KMT2A) were identified as gene biomarkers. The elastic net diagnostic classifier accurately distinguished active TB from latent. The validation analysis confirmed that our findings had high generalizability in different host background cases.Conclusion: The findings of this study provided novel insight into the underlying mechanisms of TB activation and identifying prospective biomarkers for clinical applications.

Excessive inflammatory responses contribute to the pathogenesis and lethality of highly pathogenic human coronaviruses, but the underlying mechanism remains unclear. In this study, the N proteins of highly pathogenic human coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), middle east respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were found to bind MASP-2, a key serine protease in the lectin pathway of complement activation, resulting in excessive complement activation by potentiating MBL-dependent MASP-2 activation, and the deposition of MASP-2, C4b, activated C3 and C5b-9. Aggravated inflammatory lung injury was observed in mice infected with adenovirus expressing the N protein. Complement hyperactivation was also observed in SARS-CoV-2-infected patients. Either blocking the N protein:MASP-2 interaction, MASP-2 depletion or suppressing complement activation can significantly alleviate N protein-induced complement hyperactivation and lung injury in vitro and in vivo. Altogether, these data suggested that complement suppression may represent a novel therapeutic approach for pneumonia induced by these highly pathogenic coronaviruses.

Objective: Increasing evidence shows that dysregulated RNA binding proteins (RBPs) modulate the progression of several malignancies. Nevertheless, their clinical implications of RBPs in HBV-related hepatocellular carcinoma (HCC) remain largely undefined. Here, this study systematically analyzed the associations of RBPs with HBV-related HCC prognosis.Methods: Based on differentially expressed RBPs between HBV-related HCC and control specimens, prognosis-related RBPs were screened by univariate analyses. A LASSO model was then created. Kaplan-Meier curves, ROCs, multivariate analyses, subgroup analyses and external verification were separately applied to assess the efficacy of this model in predicting prognosis and recurrence of patients. A nomogram was created by incorporating the model and clinical indicators, which was verified by ROCs, calibration curves and decision curve analyses. By CIBERSORT algorithm, the association between the risk score and immune cell infiltrations was evaluated.Results: Totally, 54 RBPs were distinctly correlated to prognosis of HBV-related HCC. An 11-RBP model was created, containing POLR2L, MRPS12, DYNLL1, ZFP36, PPIH, RARS, SRP14, DDX41, EIF2B4, and NOL12. This risk score sensitively and accurately predicted one-, three- and five-year overall survival, disease-free survival, and progression-free interval. Compared to other clinical parameters, this risk score had the best predictive efficacy. Also, the clinical generalizability of the model was externally verified in the GSE14520 dataset. The nomogram may predict patients’ survival probabilities. Also, the risk score was related to the components in the immune microenvironment.Conclusion: Collectively, RBPs may act as critical elements in the malignant progression of HBV-related HCC and possess potential implications on prognostication and therapy decision.