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.

Thalassemia is a group of anemias that result from inherited defects in the production of the beta chain of hemoglobin. It is stabilized by gamma globin, which combines to form fetal hemoglobin. One therapeutic approach is to target histone deacetylase (HDAC), which plays an important role in controlling beta thalassemia. This study sought to identify a natural inducer for treating this disease.

Twenty-five Andrographis paniculata compounds were screened using Schrödinger Suite 2020 (Maestro 12.3) for ligand preparation, grid generation, glide extra precision docking and molecular mechanics/generalized born surface area scoring. The HDAC2 crystal structure (Protein Data Bank ID: 4LXZ) was prepared by removing crystallographic water molecules and performing restrained minimization. Top-scoring complexes were subjected to 5-ns molecular dynamics simulations in GROMACS 2019 using the optimized potentials for liquid simulations force field, three interaction site point charge solvation, and standard neutralization and equilibration protocols. Absorption, distribution, metabolism, and excretion properties were predicted using QikProp.

Among the twenty five screened compounds, SRJ09 derivative of andrographolide, ranked among the top candidates based on glide extra precision docking and molecular mechanics/generalized born surface area scores and was therefore selected for further analysis. SRJ09 showed favorable binding to the HDAC2 active site, with interactions comparable to the reference inhibitor 20Y. Absorption, distribution, metabolism, and excretion predictions indicated acceptable drug-likeness, and molecular dynamics simulations demonstrated stable SRJ09–HDAC2 complex behavior over 5 ns.

We concluded that beta thalassemia may benefit from the use of andrographolide, and SRJ 09 as prospective HDAC2 inhibitor drugs that are favourable and efficacious and that generate fetal hemoglobin. Therefore, this bioactive compound is worth further investigation using in vitro and in vivo studies.

Comparative data on sequential transarterial chemoembolization (TACE) after stereotactic body radiation therapy (SBRT) in recurrent hepatocellular carcinoma (HCC) remain limited. This study aimed to evaluate the efficacy of this combination.

We retrospectively reviewed 152 patients with recurrent HCC who met predefined eligibility criteria; 109 received SBRT alone and 43 received SBRT plus TACE. To minimize selection bias, a 2:1 propensity score matching was performed, resulting in 68 patients in the SBRT-alone group and 36 in the SBRT plus TACE group for the final comparative analysis. Overall survival, progression-free survival, and local control were assessed using the Kaplan-Meier method.

The SBRT plus TACE group was associated with numerically higher survival rates, although this difference did not reach statistical significance. The cumulative one-, three-, and five-year overall survival rates were 91.2%, 76.3%, and 61.8% for SBRT alone, compared to 100.0%, 86.1%, and 77.5% for the combination therapy ( p = 0.069). The corresponding progression-free survival rates were 73.1%, 51.1%, and 32.3% versus 88.9%, 58.1%, and 52.3% ( p = 0.091). No acute grade ≥3 toxicities were observed in either group.

In this exploratory analysis of recurrent HCC, the combination of SBRT and TACE demonstrated a favorable trend toward improved survival compared with SBRT alone, without an increase in severe toxicity. While these findings did not reach statistical significance, they establish the safety profile of the combined approach and provide preliminary evidence supporting its potential therapeutic role. This hypothesis-generating study justifies and informs the design of larger, prospective trials to definitively evaluate the efficacy of this regimen.

Despite rapid advances in computational biology and regulatory reforms encouraging the reduction of animal use, a clear synthesis of how artificial intelligence (AI)-driven polypharmacology can function as a scientific and ethical bridge between traditional in vivo pharmacology and human-relevant drug development remains lacking. The shift from cage-based experimentation to code-based predictive modeling presents both opportunities and unresolved challenges in biological interpretation, regulatory acceptance, and pharmacology education. Therefore, this review aims to critically examine the transition toward AI-enabled, human-centric drug discovery within the framework of the 3R principles (Replacement, Reduction, and Refinement). Specifically, it explores (i) the global regulatory and ethical drivers accelerating non-animal methodologies, (ii) the scientific and educational gaps emerging from reduced dependence on animal models, and (iii) the role of AI and deep learning in reconstructing biological complexity through multi-omics integration and predictive toxicity modeling. By analyzing emerging AI platforms and computational strategies, this review highlights how AI-driven polypharmacology may offer a scalable, ethical, and precision-oriented framework for future pharmacological research.

Perioperative anaphylaxis is a rare, life-threatening, iatrogenic condition that predominantly arises following anesthesia. The unique context of this condition, characterized by the concurrent administration of multiple drugs, patient draping, and altered physiological states, presents significant diagnostic and therapeutic challenges, contributing to a higher mortality rate compared to anaphylaxis in other settings. This narrative review synthesizes the evidence to delineate the evolving etiology, pathophysiology, atypical clinical presentation, evidence-based immediate management, and strategic prevention of perioperative anaphylactic reactions. The primary causative agents include neuromuscular blocking agents, antibiotics, and latex, with emerging culprits such as chlorhexidine, dyes, and novel agents like remimazolam. Diagnosis is complicated by the paucity of cutaneous signs; thus, cardiovascular collapse combined with a low end-tidal carbon dioxide level has emerged as a useful supportive diagnostic indicator that requires integration with the clinical context. Immediate management prioritizes the prompt administration of epinephrine and aggressive fluid resuscitation. Subsequent allergological investigations, primarily via skin testing and serum tryptase/histamine measurement, are paramount for identifying the causative agent and preventing its recurrence. Prevention strategies emphasize meticulous history-taking, risk stratification, and the creation of latex-free environments. Future directions must focus on establishing global surveillance networks, exploring novel biomarkers and risk factors such as the circulating microbiome—a preliminary but promising area of research—and enhancing team preparedness through simulation training to improve patient safety outcomes.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has become one of the leading causes of chronic liver diseases in China, imposing a substantial and growing burden on the healthcare system. Considering the large number of individuals affected by MAFLD and the gap in disease management capacity at the primary care level, standardized guidance tailored to primary healthcare settings is urgently needed. In response, the Chronic Disease Management Branch of the China Medical Biotechnology Association convened a multidisciplinary working group incorporating hepatologists, general practitioners, and other specialists to initiate the first China national Guidelines for Diagnosis and Management of Metabolic Dysfunction-associated Fatty Liver Disease in Primary Care (2025). These guidelines provide recommendations and suggestions covering screening, risk assessment, diagnosis, treatment, referral pathways, and follow-up tailored for primary care institutions, thereby improving the long-term outcomes for the population with MAFLD and comprehensively strengthening the role of primary healthcare in chronic liver disease management.