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.

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.

Nitric oxide (NO) is a crucial regulator of hepatic and systemic vascular tone. Abnormal distribution of NO in various anatomical locations is a pathogenetic characteristic of portal hypertension. Under normal portal pressure conditions, liver sinusoidal endothelial cells produce NO, which promotes both vasodilation and hepatic stellate cell relaxation. In portal hypertension, endothelial dysfunction, imbalance of asymmetric dimethylarginine levels, and production of superoxide result in impaired intrahepatic NO availability, leading to activation and contraction of hepatic stellate cells and worsening portal hypertension. Excess extrahepatic NO levels in the splanchnic vasculature result in systemic vasodilation, hyperdynamic circulation, and collateral vascular formation, worsening portal pressure. Abnormal clearance and production of NO can lead to extrahepatic complications, including hepatorenal syndrome and hepatopulmonary syndrome. Therapies including statins, phosphodiesterase-5 inhibitors, and midodrine have been developed to restore NO homeostasis but have achieved only partial success in modulating NO production, bioavailability, and distribution. The aim of this review is to update the understanding of the mechanisms and effects of NO dysregulation in cirrhosis as they relate to current and future therapeutic options.

Chronic hepatitis B patients with baseline hepatitis B surface antigen (HBsAg) <1500 IU/mL are considered as the favorable population for achieving functional cure. This trial aimed to explore a treatment strategy to help the unfavorable population characterized by high HBsAg levels (>3000 IU/mL), hepatitis B e antigen-negative status, and normal alanine transaminase levels in the indeterminate phase (HBeIP), transition to the favorable group.

In this investigator-initiated, open-label clinical trial, we randomly assigned participants aged 18 to 60 years with HBeIP characteristics to receive either tenofovir disoproxil fumarate (TDF) monotherapy (monotherapy group) or pegylated interferon alfa-2b (Peg-IFNα-2b) plus TDF (combination group). The primary endpoints were the HBsAg loss rate and the proportion of participants with HBsAg <1,500 IU/mL through week 96.

From May 2021 to November 2023, we enrolled 263 participants, with 131 randomly assigned to the combination group and 132 to the monotherapy group. In the primary analysis, none of the 132 participants (0%) in the monotherapy group achieved HBsAg loss, compared with 10 of 131 (7.6%) in the combination group (P = 0.001). Through week 96, 48.9% (64/131) of participants in the combination group achieved HBsAg <1,500 IU/mL, and a reduction in HBsAg level greater than 1 log10 IU/mL between baseline and week 24 was an independent predictor of this endpoint (Odds Ratio = 16.957, 95% Confidence Interval: 3.002–95.797, P = 0.001). In contrast, only two participants (1.5%) in the monotherapy group achieved HBsAg <1,500 IU/mL.

Compared with TDF monotherapy, combination therapy with Peg-IFNα-2b and TDF significantly improved both HBsAg <1,500 IU/mL and HBsAg loss rates in HBeIP patients.

The impact of baseline liver fibrosis severity on the effectiveness of pegylated interferon (Peg-IFN) combined with nucleos(t)ide analogs (NAs) in the treatment of hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) has not been fully clarified. This study aimed to investigate whether the effectiveness of this combination therapy differed according to the severity of baseline liver fibrosis.

A total of 172 HBeAg-positive CHB patients receiving Peg-IFN plus NAs were stratified according to non-invasive fibrosis markers (aspartate aminotransferase-to-platelet ratio index [APRI] and fibrosis-4 index [FIB-4]) into three groups: no significant fibrosis (n = 75), significant fibrosis (n = 70), and advanced fibrosis/cirrhosis (n = 27). The primary outcome was the HBeAg clearance rate at 24 months of treatment. Secondary outcomes included the hepatitis B surface antigen (HBsAg) clearance rate, the rate of HBsAg level decline > 1.0 log10, virological response, and improvement in non-invasive fibrosis indices.

At 24 months, HBsAg clearance and complete virological response rates were comparable across the three groups. Cumulative HBeAg clearance rates differed significantly (log-rank P = 0.027): 16.00%, 30.00%, and 40.74% in the three groups, respectively, with Group 3 higher than Groups 1 and 2. Multivariate analysis identified a significantly higher likelihood of HBeAg clearance in Group 3 versus Group 1 (adjusted odds ratio = 6.373, 95% confidence interval: 1.288–31.531, P = 0.023). Additionally, analysis of liver fibrosis outcomes showed that patients with more severe baseline fibrosis had a higher proportion of improvement in non-invasive fibrosis indices, with 95.00% in Group 3, while 42.98% of the overall cohort achieved fibrosis improvement.

Baseline fibrosis severity is associated with higher HBeAg clearance and greater improvement in non-invasive fibrosis indices during Peg-IFN plus NAs therapy in HBeAg-positive CHB.

Cervical cancer is a major malignancy that threatens women’s health, and early screening is a core strategy for reducing its incidence and mortality. Multimodal fusion artificial intelligence (AI) pathological diagnosis models integrate multidimensional data—including cytological images, colposcopic images, whole-slide histopathological images, clinical data, and molecular testing results—and may enhance the detection sensitivity, grading accuracy, and screening efficiency for early cervical cancer and precancerous lesions. However, traditional cervical cancer screening methods face limitations such as high subjectivity, reliance on single-source information, relatively low efficiency, and insufficient primary care resources. Furthermore, existing reviews mostly focus on single-modal AI models or specific technical aspects, lacking a comprehensive analysis of the full technical framework and clinical translation pathways of multimodal fusion models. This review aims to comprehensively present the development and application of multimodal fusion AI models in pathological diagnosis for early cervical cancer screening. Specifically, it comprehensively details the technical architecture, data modalities, and fusion strategies—including deep learning, attention mechanisms, and cross-modal alignment techniques—that enable the complementary representation of morphological, clinical, and molecular information. Additionally, the review integrates recent advances in clinical applications and evaluates current translational challenges, providing insights into clinical validation pathways to bridge technological innovation and practical healthcare delivery. In conclusion, with further technological refinement and clinical validation, multimodal fusion AI may become a useful tool for improving the precision and efficiency of cervical cancer screening and prevention, and may inform the standardized application and translational research of AI technology in this field.

Bladder cancer (BC) remains a major public health concern in China, but comprehensive and up-to-date assessments of its burden and temporal patterns remain limited. This study aimed to systematically evaluate the current burden, temporal trends, and future projections of BC in China using data from the Global Burden of Disease Study 2023.

Data on BC incidence, mortality, disability-adjusted life years, and risk-attributable mortality in China from 1990 to 2023 were extracted from the Global Burden of Disease Study 2023. Temporal trends were assessed using Joinpoint regression, with a maximum of six joinpoints allowed, to estimate annual percentage changes and average annual percentage changes. Age-period-cohort models based on log-linear Poisson regression were used to examine age, period, and cohort effects. Bayesian age-period-cohort models were then applied to project incidence and mortality rates to 2030 while accounting for age-period-cohort effects and demographic changes.

From 1990 to 2023, crude incidence, mortality, and disability-adjusted life year rates increased, whereas age-standardized rates generally declined (average annual percentage changes = −0.32%, −1.31%, and −1.62%, respectively). In 2023, an estimated 38.06% and 10.37% of bladder cancer deaths were attributable to smoking and high fasting plasma glucose, respectively. Recent upward trends were nevertheless observed across all three indicators, particularly for incidence and mortality during 2020–2023 (annual percentage changes = 5.05% and 4.39%, respectively). Local drifts were negative in most age groups but approached or exceeded zero in the oldest groups. The incidence local drift was 0.35% (95% confidence interval [CI]: −0.07%, 0.78%) in the 85–89-year age group and 0.64% (95% CI: −0.31%, 1.61%) in the 90–94-year age group, whereas the corresponding mortality local drifts were −0.70% (95% CI: −0.97%, −0.43%) and −0.18% (95% CI: −0.72%, 0.36%), respectively. Compared with the reference period (2004–2008), the relative risks for incidence and mortality in 2019–2023 were 0.95 (95% CI: 0.91–0.98) and 0.75 (95% CI: 0.71–0.78), respectively. Compared with the reference cohort (1951–1956), earlier birth cohorts had elevated risks; in the 1901–1906 cohort, the relative risks were 1.13 (95% CI: 0.82, 1.57) for incidence and 2.10 (95% CI: 1.75, 2.52) for mortality. During 2024–2030, both crude incidence and crude mortality rates were projected to increase further.

Despite long-term declines in age-standardized rates, BC remains a substantial burden in China, and recent upward trends warrant attention. These findings support targeted primary prevention and risk-stratified early-detection strategies for high-risk populations.

Metabolic dysfunction–associated steatotic liver disease (MASLD) is increasing rapidly, yet regional differences in burden and care quality remain unclear. This study aimed to compare regional incidence, mortality, and disability; evaluate care quality; identify key determinants; and project future incidence.

We analyzed the Global Burden of Disease 2023 estimates of MASLD incidence, deaths, and disability-adjusted life years from 1990 to 2023 by age, sex, country, and region. Age-standardized rates were assessed using joinpoint regression. A composite Quality of Care Index (QCI) was derived through principal component analysis. Gradient boosting models with SHapley Additive exPlanations interpretation identified key predictors, and Bayesian age–period–cohort models generated incidence projections.

In 2023, South and East Asia had the largest numbers of new cases, while North Africa and the Middle East and Andean Latin America recorded the highest age-standardized incidence, mortality, and disability rates. Eastern Europe and Andean Latin America showed sustained increases in mortality and disability despite moderate incidence growth. QCI values were lowest in South Asia, Western Sub-Saharan Africa, and Eastern Europe. High body mass index and fasting plasma glucose were prominent contributors in comparative risk attribution analyses, and machine learning models identified age and calendar year as the strongest predictors of modeled burden patterns. Incidence is projected to continue increasing through 2050, particularly in India and China.

MASLD burden and care quality vary widely across regions. Low-QCI regions show higher mortality and disability, unfavorable metabolic risk profiles, and delayed detection patterns. Strengthening prevention, early case finding, fibrosis assessment, and treatment access may slow MASLD progression.