Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) constitutes a viral persistence reservoir that sustains chronic infection. Although the DNA damage response (DDR) facilitates cccDNA biogenesis, its role in regulating cccDNA stability remains unclear. By intersecting published cccDNA-associated proteomic datasets with known DDR-related host factors, we identified heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) as a novel restriction factor that binds cccDNA and suppresses HBV replication by promoting cccDNA degradation. Mechanistically, hnRNPA2B1 interacted with the G-quadruplex (G4) structure of cccDNA, with preference for G4-1, G4-7, and G4-10, and leads to the recruitment of the cytidine deaminase APOBEC3B by its prion-like domain (PrLD), thereby inducing C>T and G>A hypermutations and initiating cccDNA decay. Notably, HBV counteracts this defense mechanism through HBx-mediated hnRNPA2B1 polyubiquitination and proteasomal degradation, revealing a viral evasion strategy that perpetuates cccDNA persistence. These findings reveal a G4-dependent surveillance axis wherein hnRNPA2B1 directs APOBEC3B-mediated cytidine deamination to destabilize cccDNA while identifying HBx-induced hnRNPA2B1 ubiquitination as a viral countermeasure. This mechanistic duality not only elucidates a critical virus-host interaction governing cccDNA persistence but also provides a promising therapeutic target for the treatment of HBV infection.

There are individual differences in the efficacy of glucocorticoid therapy for hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Annexin A3 (ANXA3), as a potential biomarker, may be associated with the clinical outcomes of glucocorticoid therapy in HBV-ACLF patients. We enrolled 108 HBV-ACLF patients receiving glucocorticoid therapy to assess the effects of glucocorticoid therapy on ANXA3 mRNA and methylation levels in peripheral blood mononuclear cells. At the same time, clinical parameters during therapy were collected. In HBV-ACLF patients who survived, ANXA3 expression significantly decreased after glucocorticoid therapy, while methylation levels increased. No significant changes were observed in non-survivors. Logistic regression analysis of 90-day follow-up further indicated that ANXA3 methylation levels could serve as an independent predictor of glucocorticoid treatment response, with its elevation significantly correlating with favorable clinical outcomes. In HBV-ACLF patients, ANXA3 methylation levels were associated with clinical outcomes following glucocorticoid therapy, suggesting its potential as a candidate therapy-associated prognostic biomarker.

Hepatitis B-associated liver failure (HBV-LF) is a severe hepatic disease induced by hepatitis B virus infection, characterized by massive hepatocyte necrosis, rapid liver dysfunction, uncontrolled inflammation, bile acid metabolism disorders and immune microenvironment imbalance. It has a high short-term mortality of 40%-70% worldwide. Current mainstream treatments, including antiviral and organ support therapies, only control viral replication and maintain organ function, but cannot effectively reverse the excessive inflammatory cascade and metabolic disorders that drive HBV-LF progression. This review systematically summarizes the molecular mechanisms by which GPBAR1 regulates the four core pathological processes of HBV-LF: uncontrolled inflammation, massive hepatocyte apoptosis, bile acid metabolism disorders and hepatic microcirculation disturbance, and clarifies its value as a potential therapeutic target. G protein-coupled bile acid receptor 1 (GPBAR1/TGR5) is a key membrane receptor for bile acids and critically regulates hepatic physiology and pathology. Given the limited direct evidence in HBV-LF, we cautiously extrapolate relevant mechanisms from chronic hepatitis B, acute liver injury and metabolic liver diseases based on shared pathological features, while noting that these mechanisms require further validation in HBV-LF models and clinical samples. We review the structure, distribution, activation and signaling pathways of GPBAR1, focusing on its protective role in HBV-LF: inhibiting excessive inflammation via NF-κB and Keap1-Nrf2 pathways, reducing hepatocyte apoptosis through mitochondrial and PI3K/Akt pathways, maintaining bile acid balance by regulating CYP7A1/CYP8A1, and improving hepatic immunity and microcirculation via NKT, CCL2/CCR2 and ET-1 axes. Abnormal GPBAR1 expression correlates with HBV-LF severity and poor prognosis. We also summarize preclinical progress of GPBAR1 agonists (e.g. INT-767, BAR501) and compare GPBAR1-targeted strategies with other GPCR therapies. This review provides a theoretical basis for mechanistic research and target identification of HBV-LF.

Liver diseases pose a significant challenge in global public health, and scientific prevention and treatment strategies have become particularly crucial. Silybin, a flavonoid and active ingredient extracted from the traditional Chinese medicinal herb milk thistle, is the most critical effective component in silymarin, and has clearly demonstrated potent anti-oxidative stress capabilities. This unique attribute makes it a highly promising drug candidate for treating acute hepatitis, chronic hepatitis, cirrhosis, liver cancer, and other liver diseases. In the progression of liver diseases, silybin exerts significant therapeutic effects via dual anti-oxidant and anti-inflammatory mechanisms through which it alleviates the inflammatory response in acute hepatitis, stabilizes the progression of chronic hepatitis, and promotes the benign transition from decompensated to compensated cirrhosis. This study comprehensively reviews research findings on silybin in treating liver diseases via this anti-oxidative stress mechanism over the past few decades, and offers a particular focus on the development of novel drug formulations based on the oxidative stress pathogenesis of liver diseases. These formulations target the CD44 receptor, retinol/vitamin A, CXCR4 receptor, glycyrrhetinic acid receptor, GLUT4 protein, NS5B protein, and SPARC. It also examines the current status of the anti-oxidant and anti-inflammatory applications of silybin formulations in global liver disease treatments. However, more high-quality, detailed experimental studies are needed to explore its exact efficacy and safety so as to provide a stronger scientific basis for the widespread application of silybin in liver disease treatment.

Background/Aims Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is associated with extremely high short-term mortality. In this study, we aim to assess the methylation level of Takeda G protein-coupled receptor 5 (TGR5) promoter in patients with HBV-ACLF and to explore its prognostic predictive value. Methods We enrolled 118 patients with HBV-ACLF, 92 patients with chronic hepatitis B (CHB), and 47 healthy controls (HCs) between September 2024 and November 2025 from three clinical centers in China. TGR5 methylation level in peripheral blood mononuclear cells was quantified using MethyLight. Clinical and laboratory data were also collected for analysis. Results TGR5 methylation levels were significantly elevated in patients with HBV-ACLF compared to those with CHB and HCs. Among HBV-ACLF patients, non-survivors exhibited markedly elevated TGR5 methylation levels compared with survivors at both 28 and 90 days. TGR5 methylation level was positively correlated with TBIL, PCT, WBC count and MELD score. Univariate and multivariate logistic regression analyses identified TGR5 methylation level as an independent predictor for both 28-day and 90-day prognosis in HBV-ACLF. Meanwhile, TGR5 methylation level showed superior predictive performance in predicting both 28-day and 90-day mortality compared to the MELD score alone, and their combination further enhanced predictive accuracy. Conclusions TGR5 promoter methylation level shows high predictive value for short-term mortality in HBV-ACLF and may serve as a promising biomarker for prognostic assessment.

Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is associated with a high short-term mortality rate. Therefore, early and accurate prognostic prediction is crucial for precise clinical management. This study aims to investigate the expression patterns of intercellular adhesion molecule-1 (ICAM-1) and its predictive value for the short-term prognosis of patients with HBV-ACLF. The Methylight method was used to quantitatively detect ICAM-1 promoter methylation level in peripheral blood mononuclear cells (PMBCs) of 286 participants. Meanwhile, the mRNA and plasma expression levels of ICAM-1 were determined using RT-qPCR and ELISA, respectively. The ICAM-1 promoter methylation levels in PBMCs of HBV-ACLF patients were significantly lower than those in chronic hepatitis B (CHB) patients and healthy controls (HCs), whereas the mRNA and plasma expression levels of ICAM-1 were markedly elevated. The ICAM-1 methylation levels in HBV-ACLF patients correlated with specific clinical parameters. Among HBV-ACLF patients, ICAM-1 methylation levels were significantly lower in the non-survivor groups at both 28 and 90 days. The study further revealed that ICAM-1 methylation level serves as an independent influencing factor for the prognosis of HBV-ACLF patients at 28 and 90 days. Based on ROC curve and Kaplan-Meier curves, ICAM-1 methylation levels demonstrated excellent performance in predicting 28- and 90-day mortality in patients with HBV-ACLF. In conclusion, patients with HBV-ACLF exhibit hypomethylation of the ICAM-1 promoter. The combination of ICAM-1 promoter methylation level and MELD score can effectively enhance the predictive ability for the short-term prognosis of HBV-ACLF patients.

BACKGROUND:Metabolic-associated fatty liver disease (MAFLD), particularly advanced metabolic dysfunction-associated steatohepatitis (MASH), leads to irreversible liver damage. Specnuezhenide (SPE), naturally isolated from Ligustrum lucidum Ait, has been demonstrated to exert hepatoprotective effects. However, its functional role and underlying mechanisms in MAFLD remain poorly understood. PURPOSE:This study investigated the therapeutic effects and potential mechanism of SPE on MAFLD. METHODS:MAFLD mice induced by high-fat diet (HFD) were employed to assess SPE's therapeutic effects in vivo. The impact of SPE on gut microbiota was analysed by 16S rRNA sequencing. RNA-seq analysis was conducted to uncover SPE's molecular mechanisms. Complementary in vitro investigations utilized FFA-treated HepG2 cells to systematically examine SPE's cellular-level impacts and regulatory pathways. RESULTS:The results indicated that SPE could improve hepatic steatosis, liver injury and oxidative stress in MAFLD mice. SPE treatment also affected the diversity of gut microbiota and altered their composition by decreasing the Firmicutes/Bacteroidetes (F/B) ratio. The results of 16S rRNA sequencing, RNA-seq and Western blot analysis indicated that the effect of SPE on MAFLD was related to fatty acid beta-oxidation and the PPARα signalling pathway. Moreover, in HepG2 cells, SPE reduced FFA-induced lipid accumulation and oxidative stress, which was dependent on PPARα up-regulation. CONCLUSION:This is the first study to demonstrate that SPE alleviates MAFLD and is associated with modulation of gut microbiota composition and activation of the PPARα signalling pathway. Our findings suggest a potential link between gut microbiota remodelling and PPARα-mediated fatty acid oxidation, highlighting its potential as a therapeutic candidate for MAFLD.

Hepatitis B virus (HBV) infection causes persistent hepatic inflammation, and chemokine CXCL16 serves as a key mediator in liver injury, but its epigenetic regulation in chronic hepatitis B (CHB) remains unclear. This study enrolled 217 CHB patients (113 HBeAg‑positive, 104 HBeAg‑negative) and 27 healthy controls to investigate CXCL16 promoter methylation, mRNA and protein expression, as well as their correlations with inflammatory indices and liver injury markers. The results showed that CXCL16 promoter methylation was significantly lower, while CXCL16 mRNA and serum levels were markedly higher in CHB patients, especially in HBeAg‑positive cases. CXCL16 promoter methylation was negatively correlated with CXCL16 expression, HBeAg status, ALT, AST, TNF‑α and IL‑1βlevels. ROC analysis indicated that CXCL16 promoter methylation had favorable diagnostic value for evaluating hepatic inflammatory injury in CHB patients. In conclusion, CXCL16 promoter hypomethylation is closely associated with elevated CXCL16 expression and exacerbated hepatic inflammation in CHB patients, and may serve as a potential non‑invasive biomarker for assessing CHB‑related liver inflammation. These findings enrich the epigenetic mechanism underlying HBV‑related hepatic inflammation and provide a novel target which is CXCL16 for clinical evaluation and intervention.

PURPOSE:Human health could be at risk from microwave radiation, especially for the eyes because of their unique anatomical and visual characteristics. This study aimed to investigate whether the Fushiming capsule can protect against microwave radiation-induced retinal damage, oxidative stress, and pathological vascular neovascularization. METHODS:A network pharmacology approach was adopted to identify the primary components and action targets of Fushiming with potential treatment effects on the retinal diseases. Moreover, we predicted and verified its mechanisms of action. RESULTS:Network pharmacology analysis identified 43 principal components in Fushiming, and the protein-protein interaction network analysis revealed several key targets, such as VEGFA and VCAM-1. GO enrichment analysis showed that oxidative stress was an important biological process involved in the pathophysiology of the retinal diseases. In vivo and in vitro experiments revealed that Fushiming significantly alleviated microwave radiation-induced retinal pathological damage and improved electroretinogram responses to restore retinal function. Furthermore, Fushiming significantly increased the serum concentration of superoxide dismutase, glutathione peroxidase, and catalase activities, while reducing reactive oxygen species accumulation. Fushiming markedly downregulated the expression of VEGF, VEGFA, eNOS, VEGFR2, and MMP2 proteins in tissue and cellular samples. CONCLUSION:The present results indicate that Fushiming can prevent microwave radiation-induced retinal damage by enhancing antioxidant pathways and inhibiting angiogenesis-related processes.

Mex3a has been implicated in tumor progression in several malignancies; however, its clinical significance and biological role in hepatocellular carcinoma (HCC) remain incompletely understood. Mex3a expression patterns and prognostic relevance were first explored using The Cancer Genome Atlas (TCGA) dataset. A single-institution cohort of 59 patients with HCC was then analyzed to evaluate the association between Mex3a expression and clinicopathological characteristics, overall survival (OS), and recurrence-free survival (RFS). Survival outcomes were assessed using Kaplan–Meier analysis and Cox proportional hazards regression. Functional assays in vitro and in vivo were performed to investigate the role of Mex3a in HCC progression. Mex3a was significantly upregulated in hepatocellular carcinoma tissues compared with non-tumor tissues in the TCGA cohort and was associated with poorer overall survival at the univariate level. In the clinical cohort, high Mex3a expression correlated with aggressive clinicopathological features. Multivariate Cox regression analysis demonstrated that Mex3a expression was an independent prognostic factor for overall survival after adjustment for established clinicopathological variables. In contrast, Mex3a expression was not independently associated with recurrence-free survival. Functional experiments revealed that Mex3a promoted malignant phenotypes of HCC cells in vitro and enhanced tumor progression in vivo. Mex3a is associated with aggressive tumor behavior and serves as an independent prognostic factor for overall survival, but not recurrence-free survival, in patients with hepatocellular carcinoma. These findings suggest that Mex3a may contribute to disease progression and patient outcomes in HCC.

Ischemic stroke (IS) presents a major threat to human life and health due to its high disability and mortality rates. 3-n-Butylphthalide (NBP), derived from celery seeds of the Apiaceae family native to the Mediterranean region, was first introduced in China for acute IS treatment in 2004. NBP demonstrates multiple therapeutic actions, including reconstruction of microcirculation in the cerebral ischemia area, inhibition of platelet aggregation, reduction of cerebral infarction volume, maintenance of blood-brain barrier (BBB) integrity, and enhancement of cerebral blood perfusion. However, its overall efficacy remains moderate, limited by poor water solubility and low bioavailability, which constrains its clinical application. To address these limitations, researchers have actively pursued the development of NBP derivatives and analogs, achieving notable progress. These efforts, including substituent introduction, ring opening derivatization, esterification, and atom substitution, have generated diverse NBP derivatives. Several of these derivatives have advanced to clinical studies. Specifically, potassium 2-(1-hydroxypentyl)-benzoate (PHPB), brozopentyl sodium (BZP), and XY-03-EA (ZONK1103) have reached phase II clinical trials, while (S)-2-(1-acetoxypentyl)benzoic acid L-arginine salt (AAPB) has received clinical trial approval for 2024. This review examines the structural modification and optimization of NBP over the past two decades from a medicinal chemistry perspective, aiming to facilitate the development of superior derivatives and advance cerebral ischemia treatment.

Growing evidence suggests that environmental pollutants may contribute to metabolic disorders, but their specific role in Non-Alcoholic Fatty Liver Disease (NAFLD) remains unclear. This study examines the association between multiple pollutant exposures and NAFLD risk, while exploring potential demographic variations in susceptibility. The study utilized data from the National Health and Nutrition Examination Survey (NHANES). Based on diagnostic and exclusion criteria, a total of 2092 participants were included in the study, involving 16 types of environmental pollutants categorized into three groups. The Exposome-wide association study (ExWAS) was employed to analyze the relationship between exposure to environmental pollutants and NAFLD. The study included a total of 2092 participants, of whom 709 were diagnosed with NAFLD. ExWAS analysis revealed that barium, cobalt, cesium, iodine, molybdenum, thallium, and tungsten in urine were significantly positively correlated with NAFLD. Furthermore, subgroup analysis indicated that females and individuals under 65 years old were more susceptible to NAFLD due to environmental factors. Long-term exposure to environmental pollutants may increase the probability of NAFLD occurrence, and females and individuals under 65 years old may be more susceptible to these effects.

Purpose:Acute-on-chronic liver failure (ACLF) associated with hepatitis-B-virus (HBV) is a life-threatening condition characterized by severe hepatic dysfunction. The TL1A/DR3 signaling axis modulates immune responses and contributes to hepatic inflammation. This study aimed to investigate the methylation level of TL1A/DR3 promoter, explore its ability to predict prognosis, and establish a prognostic model combined with clinical indicators. Method:Methylation status and gene expression of TL1A and DR3 were analyzed in peripheral blood mononuclear cells (PBMCs) from 714 participants using Methylight and quantitative polymerase chain reaction (qPCR). Univariate, LASSO, and multivariate analyses were performed to identify key prognostic factors for 90-day outcomes in patients with HBV-associated acute-on-chronic liver failure (HBV-ACLF) and develop corresponding prognostic models. Model performance, including calibration and clinical utility, was evaluated using receiver operating characteristic (ROC) curves, Hosmer-Lemeshow (H-L) tests, and decision curve analysis (DCA). A visual nomogram was constructed to integrate these factors for risk stratification. Result:Analysis revealed significantly reduced TL1A and DR3 promoter methylation in HBV-ACLF patients, correlating with impaired liver function and coagulation parameters. PBMCs from these patients showed elevated mRNA expression of TL1A, DR3 and IL-6 compared to other groups. Methylation levels of TL1A and DR3 demonstrated high sensitivity and specificity in predicting HBV-ACLF severity. Besides, non-survivors exhibited lower TL1A/DR3 methylation than survivors. A prognostic model integrating prothrombin time activity (PTA), procalcitonin (PCT), and TL1A/DR3 methylation demonstrated excellent performance in predicting 90-day outcomes. Conclusion:Aberrant TL1A/DR3 promoter methylation reflects the disease severity, and can serve as potential biomarkers for the risk assessment of HBV-ACLF.

Hepatitis B virus (HBV) infection can cause liver damage through oxidative stress (OS) and immune-inflammatory responses. This study aims to explore the clinical significance of fibroblast growth factor 21 (FGF21) in the development and progression of chronic hepatitis B (CHB). A total of 336 participants were recruited, including 320 CHB patients and 16 healthy controls. The expression of FGF21, immune cytokines, and OS-related molecules in peripheral blood mononuclear cells (PBMCs) was detected using real-time quantitative polymerase chain reaction. The methylation level of the FGF21 gene promoter in PBMCs was detected using TaqMan probe-based quantitative methylation-specific PCR. The expression level of FGF21 in the peripheral blood of CHB patients was higher than that of HC, but the methylation level of the FGF21 promoter was lower than that of HC, especially in patients during the immune activation phase. The mRNA expression levels of CXCR3 and CCL5 in PBMCs of CHB patients during the immune activation and reactivation phases were higher than those in other clinical stages. Single-cell analysis revealed that CXCR3 and CCL5 expression in the immune tolerance and immune activation phases with high HBsAg expression was closely related to T lymphocytes (T cells) and natural killer cells (NK cells) and was highly expressed in CD4 and CD8 T cells and NK cells. In addition, the mRNA expression levels of Nrf2 and GPX4 in the reactivation phase were higher than those in other clinical stages. The mRNA expression level and methylation level of FGF21 in PBMCs of CHB patients were correlated with the viral load, immune inflammation, and OS levels during the antiviral treatment course of CHB. The methylation level of the FGF21 promoter has the potential to become a non-invasive biomarker for monitoring the progress of antiviral treatment in CHB.IMPORTANCEThis study conducted an in-depth exploration of the application of methylation detection technology, analyzing its value and driving mechanism in the oxidative stress and immune-inflammatory balance during the course of chronic hepatitis B. The study analyzed the methylation patterns of the FGF21 promoter and the expression levels of its receptor FGFR1, as well as the expression levels of chemokines CXCR3, CCL5, and oxidative stress factors GPX4 and Nrf2 in the immune tolerance period, immune clearance period, immune control period, and reactivation period of chronic hepatitis B. It clarified the association between these molecules and the FGF21/FGFR1 axis and revealed the synergistic or antagonistic mechanisms of these molecules in the oxidative stress and inflammatory vicious cycle. At the same time, this study also explored the value of FGF21 promoter methylation in disease diagnosis and prognosis, providing a theoretical basis for evaluating the antiviral treatment effect and disease progression of chronic hepatitis B.

BACKGROUND:Existing assessment systems for chronic hepatitis B (CHB)-associated liver fibrosis (LF) exhibit insufficient accuracy, thereby requiring further improvements. AIM:To investigate the association of LF staging with hepatitis B core antibody (HBcAb), hepatitis B virus DNA (HBV-DNA), and hepatitis B surface antigen (HBsAg) in patients with CHB. METHODS:We selected 120 patients with CHB receiving treatment in Hangzhou Linping District First People's Hospital from January 2020 to June 2024. Participants were allocated into the mild (F0-F1, n = 52) and moderate-to-severe groups (F2-F4, n = 68) following the rigorous LF staging criteria. HBcAb, HBV-DNA, and HBsAg concentrations were measured. Pearson correlations were employed to examine the correlations of HBcAb with HBV-DNA and HBsAg, whereas Spearman correlation analysis was conducted to identify the associations of the three with LF staging. Receiver operating characteristic (ROC) curves were further used to analyze the performance of these biomarkers in diagnosing LF stages. Furthermore, binary logistic regression analysis was conducted to determine the association of these three with LF progression in CHB. RESULTS:Markedly increased HBcAb and notably decreased HBV-DNA and HBsAg were observed in moderate-to-severe cases vs their mild counterparts. A positive correlation was observed between HBV-DNA and HBsAg, whereas both markers were inversely associated with HBcAb. Moreover, LF staging exhibited a significant positive correlation with HBcAb and an inverse connection with HBV-DNA and HBsAg. The receiver operating characteristic analysis revealed area under the curve values of 0.715, 0.799, and 0.662 for HBcAb, HBV-DNA, and HBsAg in diagnosing LF staging, respectively. Combining these markers improved the area under the curve to 0.851. The final analysis identified HBcAb as promoting fibrosis advancement (odds ratio = 2.765), whereas HBV-DNA demonstrated protective properties (odds ratio = 0.247). CONCLUSION:HBcAb is negatively correlated with HBV-DNA and HBsAg but positively associated with LF staging. All three markers are valuable in assessing LF staging, and their combined use presents the highest diagnostic efficacy. Importantly, a high HBcAb/low HBV-DNA profile markedly increased fibrosis progression risks in CHB-affected individuals.

BackgroundGlutathione peroxidase 3 (GPX3) is a strong antioxidant. While elevated GPX3 levels are linked to diverse pathologies, its role in liver failure (LF) remains underexplored. This study investigates GPX3’s diagnostic potential and mechanistic contributions to LF pathogenesis.MethodsWe integrated two high-quality liver tissue datasets (GSE38941 and GSE14668) from the Gene Expression Omnibus (GEO) database. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were conducted to identify potential biomarkers associated with liver failure. The Comparative Toxicogenomics Database was used to predict the function of GPX3. In addition, in our study, we verified the target gene mRNA expression level in 40 patients with acute or chronic acute liver failure (ACHBLF) by RT-QCPR experiment and detect the methylation status of GPX3 promoter of ACHBLF patients with methylation specific PCR (MSP).ResultsThe results demonstrate that GPX3 drives pathogenic mechanisms in liver failure through oxidative stress-related pathways (e.g., collagen cross-linking, extracellular matrix remodeling) and immune dysregulation (e.g., macrophage activation, PD-1/CTLA-4 signaling). CPX8, PRDX6, GPX4, GSS, GSR, TXN, GPX7, PPARGC1A, ALOX15, and ALOX5 have been identified as key immune-related genes. Furthermore, there were significant differences in immune cell infiltration between the high and low expression groups of GPX3 groups. Immune infiltration analysis demonstrated strong correlations between GPX3 expression and key immune markers (p < 0.05), suggesting its role in modulating inflammatory responses. Additionally, GPX3 increased susceptibility to aerosols, cyclosporin and dexamethasone was observed in patients with elevated levels of GPX3. The mRNA expression of GPX3 was much higher in ACHBLF patients than in other groups. In ACHBLF patients, the group with GPX3 methylated promoter had higher mortality than those without.ConclusionIn conclusion, GPX3 is a promising diagnostic biomarker for liver failure. Its promoter methylation status may serve as a prognostic indicator, highlighting its therapeutic potential.

Hepatitis B virus (HBV) infection is a global public health challenge that alters the immune microenvironment of the liver and drives disease progression by triggering chronic inflammation that leads to hepatic cell death through multiple programmed cell death (PCD) modalities. Due to the persistence of covalently closed circular DNA in hepatocytes, there is a lack of curative drugs that can completely eradicate HBV. Therefore, revealing how HBV infection leads to changes in the hepatic immune microenvironment, as well as searching for specific molecular targets, is crucial for controlling the onset and progression of chronic hepatitis B (CHB). In this study, we used the single sample gene set enrichment analysis and CIBERSORT algorithms to assess immune cell infiltration in the livers of CHB patients. With three advanced machine learning algorithms, random forest, least absolute shrinkage and selection operator, and selected support vector machine recursive feature elimination, we identified the PCD signature genes associated with CHB from the candidate genes. We further validated that ubiquitin-specific peptidase 21 could differentiate CHB patients with different natural courses by receiver operating characteristic analysis. These findings enhance our understanding of the mechanisms of HBV infection.

Objectives:To establish and validate a multi-parameter model for the prediction of early recurrence in patients with hepatitis B-associated hepatocellular carcinoma (HBV-HCC) after microwave ablation. Methods:This study retrospectively reviewed the clinical features and preoperative magnetic resonance imaging (MRI) scans of 166 patients with HBV-HCC who underwent microwave ablation at two hospitals. The training cohort comprised 116 patients from the first hospital (n = 116; mean age, 56 years; 84 male patients), while 50 patients from the second hospital constituted the external validation cohort (n = 50; mean age, 60 years; 38 male patients). A transformer-based deep learning network was used to fuse images from multi-sequence MRI and predict recurrence within 1 year after microwave ablation. Additionally, a nomogram based on deep learning radiomics and clinical features was developed and externally validated in a validation group from a second hospital. Results:The combined model was better than the clinical model and MRI model in predicting early recurrence of hepatitis B-associated hepatocellular carcinoma within 1 year after microwave ablation. Nomograms based on joint models include aspartate aminotransferase, portal hypertension, and deep learning-based radiomics scores. The areas under curves of the models in the training group and the validation group were 0.868 (95% CI: 0.793-0.924) and 0.842 (95% CI: 0.711-0.930), respectively, indicating high prediction ability. The results of decision curve analysis showed that the combined model had good clinical application value and correction effect. Conclusions:Our nomogram combined with clinical features and preoperative magnetic resonance imaging features effectively predicted early recurrence of hepatitis B-associated hepatocellular carcinoma within 1 year after microwave ablation.