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.

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.

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.

Despite the surging global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and related liver fibrosis, effective treatments remain limited. While the traditional Chinese medicine Juanyu-Xiaozhi Formula (JYXZF) is used against MASLD, its bioactive components and mechanisms are poorly understood. This study aimed to investigate the therapeutic effects of JYXZF and elucidate its underlying mechanisms of action.

The constituents of JYXZF were characterized using ultra-high-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Its efficacy was evaluated in a rat model of metabolic dysfunction-associated steatohepatitis (MASH) induced by a high-fat/calorie diet with high-fructose/high-glucose water, utilizing serum biochemistry, histology, and glucose/insulin tolerance tests. Mechanistic validation was performed in free fatty acid-treated human hepatocellular carcinoma cell line HepG2 (HepG2) cells and HepG2/human hepatic stellate cell line LX-2 (LX-2) co-culture models using luciferase assays, chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR), and activator protein 1 (AP-1) overexpression rescue experiments. The functional relevance of stearoyl-CoA desaturase 1 (SCD1) was further assessed in vivo through liver-targeted adeno-associated virus (AAV)-mediated Scd1 overexpression.

Flavonoids were identified as the main bioactive constituents. JYXZF administration alleviated metabolic dysfunction, reduced hepatic lipid accumulation, and attenuated inflammation and fibrosis in MASH rats. Multi-omics integration and machine learning-assisted target prioritization identified lipid metabolic and inflammatory pathways. Among these pathways, we selected the AP-1/peroxisome proliferator-activated receptor gamma (PPARγ)/SCD1-related lipogenic pathway for functional validation. Target perturbation experiments supported the functional involvement of AP-1 in the regulation of the PPARγ/SCD1 pathway and its contribution to the anti-steatotic effects of JYXZF.

JYXZF alleviates MASLD-associated steatosis and fibrosis via the AP-1/PPARγ/SCD1-related lipogenic axis, demonstrating its therapeutic potential for MASLD/MASH and providing a mechanistic basis for future clinical applications.

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.

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.

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.