Chronic pancreatitis is an inflammatory disease and is difficult to manage despite advancements in medical science. This study examined the effect of water/ethanol extracts of Justicia carnea leaves on oxidative stress and glucagon expression in a mouse model of chronic pancreatitis induced by trinitrobenzenesulfonic acid (TNBS).

Twenty-five male Swiss albino mice were randomized and treated intrarectally with vehicle (the control group) or TNBS. Some TNBS-treated mice were treated orally with 200 mg/kg or 400 mg/kg J. carnea extracts, or with the positive control, 500 mg/kg sulfasalazine, every other day on three occasions. Oxidative stress markers and pancreatic glucagon expression were assessed.

Compared with the healthy control mice, treatment with TNBS significantly decreased the levels of pancreatic glutathione (0.89 µmol/g tissue vs. 7.16 µmol/g tissue in the control) and glutathione peroxidase activity, but significantly increased the levels of α-amylase and lipase activities, lipid peroxidation, total antioxidant capacity, and nitric oxide, as well as serum C-reactive protein (P < 0.05 for all), accompanied by severe inflammation and reduced glucagon expression in the pancreatic tissues. The toxic effects of TNBS were significantly mitigated by treatment with J. carnea extracts.

These findings provide evidence that treatment with J. carnea extracts inhibited oxidative stress and preserved glucagon expression in the pancreatic tissues of mice.

Phenylethanoid glycosides (PhGs) are water-soluble natural compounds widely distributed in the plant kingdom, attracting significant attention from medicinal chemists due to their promising potential in pharmaceutical applications. PhGs exhibit a broad range of activities, including neuroprotective, hepatoprotective, anti-inflammatory, antioxidant, and immunomodulatory effects. This review aims to update the hepatoprotective effects of total PhG extracts and individual PhG compounds, as well as the underlying mechanisms. Additionally, we describe the structural characteristics, representative PhG compounds, and their structure–activity relationships. In brief, total PhG extracts can exert synergistic protection by reducing serum alanine aminotransferase/aspartate aminotransferase levels, suppressing oxidative stress, and attenuating inflammatory responses. Representative PhGs, including acteoside (verbascoside), echinacoside, forsythoside A (also known as forsythiaside A), and cistanoside A, protect against liver injury through modulation of the Nrf2/HO-1, NF-κB, MAPK, and TGF-β/Smad pathways, thereby regulating oxidative stress, inflammation, apoptosis, fibrosis, and lipid metabolism. Structurally, PhGs consist of a phenylethyl alcohol core, cinnamoyl residues, and glycosyl moieties. Structure–activity relationship analyses indicate that caffeoyl substitution, multiple phenolic hydroxyl groups, and optimal glycosylation patterns are key determinants of hepatoprotective efficacy.

Extrahepatic cancers have been recognized as a significant outcome of metabolic dysfunction–associated steatotic liver disease (MASLD), which involves five cardiometabolic risk factors, including hypertension, and is associated with the tumorigenesis of several cancers or with anti-cancer treatment. We aimed to investigate the association between hypertension, liver fibrosis, and extrahepatic cancers in the MASLD population.

This multicenter cross-sectional study was based on a MASLD population from hospital-based databases across 11 centers nationwide in China, according to MASLD diagnostic criteria identified using keywords and ICD-10 codes. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between risk factors and extrahepatic cancers.

A total of 103,652 individuals with MASLD were identified, among whom 6,605 were diagnosed with extrahepatic cancers. The primary outcome revealed that hypertension was significantly associated with extrahepatic cancers (OR 1.14, 95% CI: 1.08–1.21), and its combination with hyperglycemia further increased this association (OR 1.36, 95% CI: 1.22–1.51). Risk factors for extrahepatic cancers included being over 40 years of age and female sex. Conversely, certain metabolism-based treatments were found to have potentially protective effects, including angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, fibrates, GLP-1 receptor agonists, and thiazolidinediones. After adjusting for confounding factors, the fibrosis-4 (FIB-4) score was associated with extrahepatic cancers. In the hypertension subgroup, FIB-4 scores of 1.30–2.66, 2.67–3.47, and ≥ 3.48 were associated with extrahepatic cancers in individuals aged 35–64 years, consistent with findings in those aged ≥ 65 years of age with FIB-4 ≥ 2.

Hypertension combined with liver fibrosis is associated with extrahepatic cancers in patients with MASLD.

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.

Predicting the malignant transformation of rectal precancerous lesions remains challenging because conventional Whole Slide Images (WSIs) capture morphological information but lack molecular insight. Multiomics data provide complementary biological signals that often precede visible morphological changes. This study aimed to develop an artificial intelligence (AI)-based multimodal framework integrating WSI and multiomics data for accurate early prediction of malignant transformation.

WSI patches (512×512 px at 20× magnification) and matched multiomics profiles were used for 450 rectal tissue samples from the publicly available The Cancer Genome Atlas dataset. A multimodal architecture was designed, employing a Vision Transformer (ViT-B/16) for WSI feature extraction and a Variational Autoencoder for multiomics representation learning. Features were fused via a cross-attention mechanism to capture inter-modality dependencies. Baseline models, including a convolutional neural network-only image model and an omics-only multilayer perceptron, were trained for comparison. Five-fold cross-validation was applied, with binary cross-entropy loss, the AdamW optimizer, early stopping, and hyperparameter tuning to ensure reproducibility.

The multimodal Vision Transformer–Variational Autoencoder fusion model outperformed unimodal baselines, achieving an accuracy of 0.892 ± 0.012 and an area under the receiver operating characteristic curve of 0.927 ± 0.009, corresponding to a 7–10% improvement over WSI-only and omics-only models. Cross-attention–based fusion improved prediction stability and classification performance, while interpretability analyses (Grad-CAM and SHAP) highlighted biologically meaningful histopathological regions and molecular feature contributions.

This study presents a robust and scalable AI-based framework for integrating WSI and multiomics data in rectal precancerous lesions. The model improves predictive precision compared with unimodal baselines and offers preliminary interpretability insights through attention mechanisms. These findings support the potential of multimodal AI for early cancer risk assessment and precision pathology.

Liver transplant rejection significantly affects patient prognosis. Myeloid-derived suppressor cells (MDSCs), known for their potent immunoregulatory functions, represent a promising target for managing liver transplant rejection. This study aimed to systematically characterize the diversity of MDSC subsets and their context-dependent functions, particularly within the context of transplant tolerance.

We analyzed clinical and murine liver transplants using single-cell RNA sequencing, bulk RNA sequencing, flow cytometry, multiplex immunohistochemistry, and co-culture assays to phenotype MDSC subsets.

Single-cell RNA sequencing analysis of human and murine samples revealed MDSC involvement in transplant rejection. In mice, MDSC scores followed a normal distribution during the first week post-transplant and correlated with clinical flow cytometry data at one month. A distinct LDLR+ monocytic MDSC (M-MDSC) subset was identified and confirmed through spatial mapping by multiplex immunohistochemistry. Flow cytometry demonstrated dynamic changes in LDLR+ M-MDSCs across tissues (liver, spleen, peripheral blood, bone marrow, and lymph nodes), with a peak during acute rejection. Co-culture experiments showed that LDLR−/− M-MDSCs exhibited reduced Arg-1/iNOS expression and an impaired capacity to induce inhibitory receptors (TIGIT, PD1, CTLA-4) or suppress effector molecules (GZMB, IFN-γ, IL-2) in CD8+ T cells.

These findings highlight the critical role of MDSCs in liver transplant rejection. LDLR+ M-MDSCs exhibited enhanced immunosuppressive properties, underscoring their potential clinical relevance in mitigating rejection and promoting immune tolerance.

Acute liver failure (ALF) is a severe hepatic injury associated with high short-term mortality. Our previous study found that 1,5-anhydroglucitol (1,5AG) levels correlate with clinical outcomes in patients with liver failure. This study aimed to explore the potential effects and mechanisms of 1,5AG in ALF.

An experimental model of ALF was established using LPS and D-GalN. 1,5AG was administered to mice by gavage before modeling. Empagliflozin was then administered to reduce 1,5AG levels in mice. Peroxisome proliferator-activated receptor alpha (PPARα) agonists were also used to explore the role of 1,5AG in mice with liver failure.

1,5AG pretreatment significantly increased ALT and AST levels, aggravated histological damage and hepatocyte apoptosis, and increased mortality in ALF mice. Transcriptomic analysis and western blot validation revealed that 1,5AG significantly inhibited the PPARα signaling pathway and its downstream target, fibroblast growth factor 21. Empagliflozin treatment reduced 1,5AG levels, alleviated liver injury and hepatocyte apoptosis, and promoted the PPARα signaling pathway in ALF. PPARα agonists effectively reversed the effects of 1,5AG on ALF, thereby alleviating liver damage, pathological injury, and hepatocyte apoptosis.

1,5AG exacerbated liver injury in ALF mice by inhibiting the hepatic PPARα pathway, thereby promoting hepatocyte apoptosis.

The long-term clinical outcomes of patients with hepatitis B virus (HBV)-related cirrhosis receiving nucleos(t)ide analog (NA) therapy according to virological response patterns remain inadequately defined. This study aimed to investigate the association between virological response patterns and clinical outcomes in a large, long-term, real-world cohort.

This retrospective–prospective cohort study enrolled patients with HBV-related cirrhosis receiving NA therapy from 2009 to 2019. According to the serum HBV DNA levels during the initial two years of antiviral treatment, patients were categorized as having a complete (CVR) or partial virological response (PVR). Patients with CVR were further stratified according to their dynamic HBV DNA changes during follow-up into maintained virological response (MVR) or virological breakthrough (VBT) patterns. The primary clinical outcomes included hepatocellular carcinoma (HCC), acute-on-chronic liver failure, and liver-related death. Secondary endpoints included recompensation and progression to decompensation. Cox proportional hazards regression was used to assess the association between virological response patterns and clinical endpoints.

In total, 1,869 patients were enrolled. During a median follow-up of seven years, the MVR, VBT, and PVR rates were 65.4%, 26.5%, and 8.1%, respectively. The cumulative serum hepatitis B surface antigen (HBsAg) clearance rate was 9.8%. Moreover, 34.9% of patients with HBsAg < 100 IU/mL at baseline experienced HBsAg clearance. Compared with patients with VBT and PVR, those with MVR had a lower five- and ten-year cumulative incidence of HCC in both the compensated (five-year: 10.1% vs. 17.0%; ten-year: 14.2% vs. 33.6%; P < 0.001) and decompensated cirrhosis subgroups (five-year: 19.5% vs. 36.7%; ten-year: 25.7% vs. 49.7%; P < 0.001). Similarly, patients with MVR also had a lower cumulative incidence of liver-related death. Additionally, a higher hepatic recompensation rate was observed in patients with MVR than in those with VBT (34.1% vs. 22.5%, P < 0.001). Importantly, patients achieving HBsAg clearance and undetectable serum HBV DNA levels (“functional cure” during ongoing NA therapy) had the lowest five- and ten-year cumulative incidence of HCC (3.9% and 8.7%, respectively).

Patients with long-term MVR exhibited a lower incidence of HCC and liver-related death in both compensated and decompensated HBV-related cirrhosis subgroups, especially those achieving “functional cure.” However, more than 30% of patients experienced PVR or VBT during long-term NA antiviral therapy. These findings highlight the importance of long-term, rigorous monitoring after initial CVR to optimize outcomes and support clinical decision-making.