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.

Diabetic cardiomyopathy (DCM), a diabetes-specific cardiovascular complication, is pathologically characterized by cardiomyocyte apoptosis, oxidative stress, inflammatory responses, and myocardial fibrosis, distinguishing it from other cardiac disorders, such as hypertension and coronary artery disease. Challenges in early diagnosis, coupled with the limited efficacy and adverse effects of current treatments, have made DCM a significant contributor to heart failure and mortality in patients with diabetes. Natural products, recognized for their diverse sources, structural variety, and multitarget therapeutic potential, have shown promise in preventing and treating DCM. Drawing on advances over the past five years, this review systematically summarizes the pharmacological effects and molecular mechanisms of natural products (e.g., flavonoids, terpenoids, phenylpropanoids, alkaloids, and polysaccharides) in the treatment of DCM, with the aim of providing a theoretical foundation for further research and drug development.

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.

Obstructive sleep apnea (OSA) is a prevalent sleep disorder characterized by intermittent hypoxia and sleep fragmentation, which may contribute to lung cancer development and progression. This review synthesizes epidemiological evidence on the association between OSA and lung cancer incidence and mortality, highlighting inconsistencies due to study design, population differences, and confounding factors such as smoking and obesity. While some studies report an increased lung cancer risk, particularly with severe nocturnal hypoxemia, others suggest no significant association or a potential protective effect. Pathophysiologically, OSA promotes oncogenesis through hypoxia-inducible factor activation, tumor immune microenvironment remodeling, exosome-mediated signaling, nuclear factor κB pathway activation, and enhanced cancer stem cell properties. Continuous positive airway pressure therapy may mitigate these effects, with evidence suggesting reduced lung cancer incidence and improved prognosis in adherent patients. This review underscores the need for standardized studies using objective diagnostics and robust confounder adjustment to clarify the OSA–lung cancer link and optimize clinical management.

Micro- and nanoplastics (MNPs) are pervasive environmental contaminants with growing recognition as potential contributors to human disease. Widespread human exposure occurs primarily through ingestion of contaminated food and water, and MNPs have been detected in multiple human tissues, including the gastrointestinal tract. Experimental evidence provides a plausible biological basis for disease associations, including impairment of intestinal barrier integrity, activation of mucosal immune pathways, and alteration of gut microbial communities caused by MNP exposure. Although human data remain limited, early studies demonstrate MNP detection in stool and suggest potential correlations with inflammatory biomarkers such as fecal calprotectin. These findings, together with mechanistic data from in vitro and animal models, raise concern that MNP exposure represents a paradigm shift in the pathogenesis or modulation of inflammatory bowel disease (IBD); however, methodological variability, small sample sizes, and contamination challenges currently limit definitive conclusions. The aim of this review is to evaluate the current understanding of MNP exposure and its impact on intestinal health, particularly in relation to IBD. We synthesize mechanistic and early clinical evidence linking MNPs to IBD and highlight critical research gaps. Future standardized exposure assessment, mechanistic validation in human systems, and longitudinal studies are essential to clarify causal relationships. Given the modifiable nature of environmental plastic exposure, advancing this field may offer new opportunities for IBD prevention and intervention.

Breast cancer (BCA) is one of the most common cancers worldwide, with a high rate of mortality and morbidity in women. This review focuses on the applications of nanotechnology, nanomaterials, and nanoparticles (NPs) in BCA, encompassing diagnosis and therapy. Nanotechnologies, nanocarriers, and nano-encapsulations versus their corresponding counterparts for BCA diagnosis and therapy have been discussed. Various drug formulations into different nanocarriers (lipid NPs, nanoemulsions, polymeric NPs, and metal-based NPs) enhanced their bioavailability and therapeutic efficacy, overcoming the limitations of conventional formulations. Additionally, clinical specialists have achieved improved outcomes in the detection and monitoring of BCA at various stages using nanotechnology, ultimately leading to an improved quality of life for patients.