The Asia-Pacific region accounts for a larger share of the hepatitis B burden than any other regions of the world, presenting a challenge to meeting the World Health Organization (WHO) 2030 elimination targets. In this study, we aimed to quantify the burden of chronic hepatitis B (CHB) and project its trends through 2030 using the Global Burden of Disease 2023 framework, thereby identifying gaps and priorities for the Asia-Pacific region to achieve WHO 2030 targets.

Using data from the Global Burden of Disease Study 2023, we analyzed CHB prevalence, mortality, and disability-adjusted life years. We evaluated temporal trends (1990–2023) using average annual percent changes and projected the 2024–2030 burden using Bayesian age-period-cohort models.

In 2023, the Asia-Pacific region accounted for 63% of global CHB cases (178.0 million), 66% of deaths (259.1 thousand), and 65% of disability-adjusted life years (8.4 million). Regional prevalence and mortality rates exceeded global averages, although childhood (<5 years) prevalence was comparatively lower (590.3 vs. 1,325.3 per 100,000). East Asia bore the highest absolute burden (99.2 million cases), and South Asia had the largest pediatric caseload. Between 1990 and 2023, Western Asia showed the steepest decline in adult prevalence (−1.99%), whereas Southeast and Central Asia exhibited upward mortality trends. Projections indicate that the Asia-Pacific region is off track to meet the WHO 2030 disease elimination targets, as the prevalence rate in children under five years remains above the 0.1% target threshold and absolute mortality is projected to increase.

The Asia-Pacific region continues to contribute the largest share of the global CHB burden and now faces persistent gaps despite progress. Although substantial progress has been made in reducing prevalence through immunization, the region is currently off track to meet the WHO 2030 targets for both incidence and mortality.

The aberrant activation of the mTOR pathway and its crosstalk with other signaling cascades represent key drivers of hepatocellular carcinoma (HCC) progression. mTOR-mediated ferroptosis suppression has been implicated in HCC resistance to chemotherapy. This study aimed to elucidate the mechanisms underlying mTOR inhibitor resistance and to evaluate the therapeutic potential of multidrug combinations in β-catenin-mutant HCC.

MHCC97H and SNU449 cells were transfected with 4EBP1WT, 4EBP1A4, or HSP90β expression plasmids and then treated with rapamycin to assess their effects on ferroptosis and rapamycin sensitivity. The role of 4EBP1 in regulating ferroptosis was further explored by Western blotting, co-immunoprecipitation, and immunofluorescence. The inhibitory effects of mTOR inhibitors (rapamycin, MLN0128), ERK inhibitors (PD901), and their combination (MLN0128 + PD901) on tumor cells were evaluated. HCC mouse models were generated via hydrodynamic tail vein injection of c-Met/β-cateninΔN90 or c-Met/β-cateninΔN90/4EBP1A4 plasmids to evaluate the therapeutic effects of the four treatment regimens.

Rapamycin more potently inhibited mTOR/RPS6 than mTOR/4EBP1 and concurrently induced ferroptosis. 4EBP1A4 promoted ferroptosis and potentiated rapamycin efficacy. Mechanistically, 4EBP1A4 competitively bound HSP90β, displacing Keap1, thereby increasing Keap1–Nrf2 complex formation and promoting Nrf2 degradation. Furthermore, rapamycin, MLN0128, PD901, and their combination reduced p-4EBP1 levels, induced ferroptosis, and inhibited HCC cell proliferation, thereby suppressing tumor growth, with the combination exhibiting the strongest effect.

4EBP1A4 enhances Nrf2 ubiquitination and degradation via the HSP90β/Keap1 axis, relieving mTOR-mediated ferroptosis suppression and synergistically improving rapamycin efficacy. Additionally, rapamycin, MLN0128, and PD901 suppress HCC progression by inducing ferroptosis, with their combination showing superior potency.

Chronic pelvic pain remains a significant clinical challenge, often refractory to conservative and interventional treatments. Superior hypogastric plexus block is an established technique; however, conventional anterior and posterior approaches may be limited by anatomical variability and potential risks to adjacent structures. Based on these anatomical findings, we propose that a posterior transosseous S1 pedicular approach represents a novel and anatomically robust corridor for accessing the superior hypogastric plexus. We hypothesize that the highly reproducible osseous anatomy of the S1 pedicle, combined with its consistent spatial relationship to the anterior sacral cortex and retroperitoneal compartment, may enable precise and fluoroscopically reproducible instrument guidance toward the plexus. Furthermore, this trajectory may mitigate the anatomical variability and procedural limitations associated with conventional anterior or paravertebral techniques while potentially reducing the risk of inadvertent injury to adjacent visceral, vascular, and neural structures. This concept is based on anatomical reasoning and fluoroscopic observations obtained during cadaveric anatomical orientation, suggesting that a transosseous trajectory through the S1 pedicle toward the anterior sacral cortex may offer improved spatial control and reproducibility compared with soft-tissue-based approaches. The proposed pathway remains conceptual and is not intended for clinical application at this stage. Further cadaveric, imaging-based, and clinical studies are required to evaluate its anatomical validity, safety, and potential clinical relevance.