The optimal management strategy for adults with immune-tolerant (IT) chronic hepatitis B infection remains undefined. This study aimed to investigate the efficacy and predictive factors of a pegylated interferon (Peg-IFN)-based treatment strategy in IT patients with chronic HBV infection.

In this pilot, open-label, prospective study, 286 patients aged 18 to 60 years with IT characteristics were enrolled and allocated to one of three groups. The combination group received Peg-IFN for 48–96 weeks, with tenofovir disoproxil fumarate (TDF) initiated at week 12 and continued through week 96 (n = 103). The monotherapy group received TDF monotherapy alone (n = 125), and the control group was monitored without therapeutic intervention (n = 58).

No patients in the control group met any predefined efficacy endpoints. Intention-to-treat analysis showed that patients in the combination group achieved significantly higher virological response rates (71.8% vs. 53.6%, p = 0.005), hepatitis B e antigen seroconversion rates (15.5% vs. 1.6%, p < 0.001), and hepatitis B surface antigen (HBsAg) loss rates (10.7% vs. 0%, p < 0.001) compared with those in the monotherapy group at week 96. In the combination group, the cumulative rate of HBsAg loss was 5.4% at week 48 and increased to 11.8% by week 96. Independent predictors of achieving either hepatitis B e antigen seroconversion or HBsAg loss were baseline age under 30 years (odds ratio = 0.217, 95% confidence interval: 0.048–0.976, p = 0.046) and a decline in HBsAg level greater than 1 log10 IU/mL by week 24 (odds ratio = 13.976, 95% confidence interval: 2.506–77.932, p = 0.003).

A Peg-IFN-based treatment strategy significantly increases response rates compared with TDF monotherapy or observation in patients with IT characteristics.

Early and accurate prognostic assessment is crucial to avoid serious disease progression in patients with liver failure. Thyroid hormone is an important metabolic regulator involved in hepatic function. This review examines in detail the pathophysiological regulation of the hypothalamic-pituitary-thyroid axis in patients with liver failure and emphasizes the importance of thyroid profiling (thyroid-stimulating hormone, T3, and T4) in prognostic assessment and risk stratification. T3 can enhance liver regeneration. The clinical application of thyroid hormone replacement therapy in patients with acute-on-chronic liver failure complicated by non-thyroidal illness syndrome is controversial. This review aims to inform clinical practice regarding the relevance of TH level assessment in liver failure and to provide novel insights into the prognostic evaluation and comprehensive care of liver failure complicated by thyroid dysfunction.

Glioblastoma remains a highly challenging malignancy with a pronounced tendency for recurrence. The hypoxic microenvironment is a key contributor to its therapy resistance. Hyperbaric oxygen therapy (HBOT), which elevates tissue oxygen pressure and reverses hypoxia, exhibits a “dual effect” in glioblastoma management. This review aims to evaluate the therapeutic potential of HBOT in glioblastoma by examining its multifaceted effects on tumor biology and treatment response. On one hand, it enhances radiosensitivity through reactive oxygen species generation, increases chemotherapy efficacy by augmenting cytotoxicity and improving vascular perfusion, and remodels the tumor microenvironment via vessel normalization, edema reduction, and immune cell modulation. Furthermore, HBOT attenuates cancer stem cell properties by downregulating stemness markers and inhibiting self-renewal capacity. On the other hand, HBOT may also promote tumor progression: oxidative stress can induce genomic instability, while concomitant activation of HIF-, NF-κB-, and VEGF-mediated pro-survival pathways may facilitate malignant cell adaptation and proliferation. Given these opposing considerations, the clinical application of HBOT in glioblastoma management remains exploratory. In conclusion, future research should focus on optimizing HBOT protocols. In addition, exploring combination with other therapeutic approaches is equally important. These efforts are essential for the safe and effective integration of HBOT into comprehensive treatment strategies for glioblastoma.

Fast inverse planning in radiosurgery planning is limited by an excessive number of isocenters, which is clinically hypothesized to be driven by the morphological irregularity of the target volume. This retrospective cross-sectional study aimed to empirically evaluate this hypothesis in vestibular schwannoma cases.

Consecutive patients diagnosed with vestibular schwannoma and receiving Gamma Knife radiosurgery in 2023 were included, and their treatment plans designed using the GammaPlan planning system were collected. Morphological irregularity–related parameters, including standard sphericity (SS), volume ratio sphericity (VRS), and the coefficient of variance of diameters (DCV), were calculated based on parameters provided by the system. Basic demographic and clinical data were collected to evaluate their impact on sphericity. The effects of different sphericity assessment methods on common treatment plan parameters were analyzed.

Treatment plans of 280 patients with vestibular schwannoma were collected. The SS, VRS, and DCV of the tumors were 0.85 (0.77–0.91), 0.46 ± 0.16, and 0.22 (0.14–0.34), respectively. Multivariate analysis showed that lesion volume, acoustic neuroma consensus on systems for reporting results grade, and age were significant factors influencing sphericity. All other planning parameters, except prescription dose and homogeneity index, were significantly correlated with sphericity. DCV was more closely correlated with SS than with VRS.

DCV may serve as a simple quantitative metric of target morphological irregularity, showing strong consistency with SS. Incorporating morphological irregularity into Gamma Knife treatment plan evaluation may help improve future planning strategies and support optimization of isocenter utilization.

The bromodomain and extra-terminal domain (BET) protein family, particularly BRD4, is critical for the control of oncogenic transcriptional programs in solid tumors. Although initial-generation BET inhibitors, such as JQ1, molibresib, and birabresib, have demonstrated preclinical efficacy in repressing MYC-dependent pathways, their clinical translation has been hampered by low monotherapy activity, pharmacokinetic heterogeneity, and dose-limiting toxicities. This review aims to update the mechanistic foundations, clinical trial results, and development of therapeutic approaches to BET inhibition in solid tumors, outlining its evolving role in the next generation of cancer treatment strategies. Various clinical trials in different phases have demonstrated heterogeneous responses among solid tumor types, with greater effects in NUT carcinoma and castration-resistant prostate cancer. Resistance mechanisms, including BRD4 isoform switching and compensatory signaling activation, emphasize the need for advanced and innovative BET-targeting modalities. BD2-selective BET inhibitors and proteolysis-targeting chimeras are likely to overcome these limitations by increasing target specificity and reducing systemic side effects. In addition, combination strategies, such as PARP inhibitors, AR antagonists, and immune checkpoint blockade, have synergistic potential to augment anticancer activity. In conclusion, this review provides a comprehensive overview of the advances, challenges, and future directions of BET bromodomain inhibition in solid tumors.

The intestinal barrier, a critical interface between the body and the external environment, is essential for maintaining internal homeostasis. Comprising mechanical, chemical, immune, and biological components, its dysfunction underpins multiple gastrointestinal pathologies. Circular RNAs (circRNAs), covalently closed non-coding RNAs, have emerged as central regulators of gut barrier homeostasis. This review synthesizes advances in circRNA roles in intestinal stem cell renewal, apoptosis-proliferation balance, microbiome interactions, and immune regulation. Key findings highlight circRNA networks operating via competitive endogenous RNA mechanisms, protein interactions, and translational potential to influence barrier function. We further discuss circRNAs as diagnostic biomarkers in inflammatory bowel disease and their therapeutic potential in barrier-related pathologies. Advances in RNA nanotechnology (e.g., lipid nanoparticles) and synthetic biology position engineered circRNAs as next-generation therapies for precision intervention in gastrointestinal disorders. Importantly, this review also critically examines the current limitations of these translational approaches, including delivery challenges, safety considerations, and the preliminary nature of many preclinical findings, providing a balanced perspective on the path from bench to bedside.