ATP-binding cassette (ABC) transporters are transmembrane proteins involved in the translocation of bilirubin, bile acids, phospholipids, and cholesterol into bile canaliculi. Mutations in particular genes encoding these transporters—including BSEP (ABCB11 gene), MDR3 (ABCB4 gene), sterolin-1 and sterolin-2 (ABCG5/8 genes), and MRP2 (ABCC2 gene)—result in a wide spectrum of liver diseases, ranging from benign conditions such as Dubin-Johnson syndrome to more severe presentations like progressive familial intrahepatic cholestasis. The severity of disease is influenced by many factors, including zygosity, mutation type, and environmental modifiers such as hormones, consanguinity, and founder effects. Homozygous and compound heterozygous mutations typically result in severe and early-onset diseases, while heterozygous single-allelic mutants generally result in milder diseases. Next-generation genetic testing has proven to have high diagnostic value and is important for prognostication. With knowledge of the underlying specific mutations, there is also potential for future targeted therapy for many severe diseases. The aim of this review is to update and discuss the hepatic diseases associated with ABC transporter mutations, the genetic and environmental effects that influence the severity of disease, typical presentations of these cholestatic hepatic diseases, diagnostic considerations, and treatment options.

Hepatic iron deposition (HID) in the reticuloendothelial system (RES) is associated with histological severity in metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to assess the interaction between the transferrin (TF)-rs1049296 C>T variant and HID patterns on the risk of significant liver fibrosis in MASLD.

We analyzed 406 adults with liver biopsy-confirmed MASLD. HID was categorized as hepatocellular, RES, or mixed, based on Perl's iron staining. The association between iron-related genetic variants and significant liver fibrosis (fibrosis stage ≥ F2) was analyzed, focusing on the interactions between single-nucleotide polymorphism genotypes and iron deposition patterns. Multivariable logistic regression analysis was used to adjust for potential confounders.

HID was detected in 271 (66.7%) patients, with hepatocellular, RES, and mixed patterns accounting for 11.1%, 18.0%, and 37.7%, respectively. A significant interaction was observed between HID and the TF-rs1049296 genotype (Pinteraction = 0.035). In multivariable analysis, male sex, hypertension, severe lobular inflammation, and mixed hepatocellular/RES iron deposition were independent predictors of significant liver fibrosis. RES deposition markedly increased the risk of significant liver fibrosis (adjusted odds ratio: 6.65; 95% confidence interval: 1.84–23.97, p < 0.05), particularly in men with isolated RES iron deposition (adjusted odds ratio: 5.26; 95% confidence interval: 1.21–22.81, p < 0.05).

The TF-rs1049296 T allele interacts with RES iron deposition to identify a MASLD subpopulation at elevated risk of progressive liver disease, providing opportunities for refined risk stratification and personalized management.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is now considered to be among the most prevalent chronic liver diseases worldwide. Its comprehensive management encompasses multiple stages, including risk assessment, early detection, stratified intervention, and long-term follow-up. Among these, improving diagnostic accuracy and optimizing individualized therapeutic strategies remain key challenges in both research and clinical practice. In recent years, artificial intelligence and smart devices have developed rapidly and have gradually been applied in the medical field, offering novel tools and pathways for MASLD risk stratification, non-invasive diagnosis, therapeutic evaluation, and patient self-management. This review summarizes the current applications of artificial intelligence and smart devices in MASLD care, highlights their benefits and limitations, and discusses future directions to support precision diagnosis and treatment strategies.

Microsatellite-stable colorectal cancer, which accounts for roughly 80–85% of cases, remains largely refractory to immune checkpoint inhibitors compared with microsatellite instability-high tumors. This review synthesizes current evidence on tumor-intrinsic and microenvironmental mechanisms underlying immune checkpoint inhibitor resistance in microsatellite-stable colorectal cancer—including low neoantigen burden and impaired antigen presentation, activation of Wnt/β-catenin and MAPK signaling that exclude T cells, an immunosuppressive cellular milieu (regulatory T cells, myeloid-derived suppressor cells, M2-like tumor-associated macrophages, cancer-associated fibroblasts), metabolic reprogramming, and gut microbiome dysbiosis—and evaluates translational strategies aimed at overcoming these barriers. Preclinical and early-phase clinical data indicate that rational, mechanism-guided combinations (vascular normalization, myeloid reprogramming, metabolic inhibitors, antigen-priming approaches, and microbiome modulation) can enhance immune infiltration and produce benefits in biomarker-defined subgroups. Moving the field forward will require biomarker-driven, adaptive clinical trials with embedded translational endpoints to optimize patient selection and manage toxicity.

The global integration of traditional medicine (TM) and modern medicine reflects a fundamental shift in healthcare aimed at delivering more holistic, culturally sensitive, and patient-centered care. With over 80% of the global population relying on some form of TM, especially in Asia, Africa, and Latin America, there is growing momentum to institutionalize TM alongside evidence-based biomedicine. Countries like India, China, and Korea have led integration through formal education, government-supported research, and clinical frameworks, while high-income countries are increasingly adopting complementary and integrative medicine models. However, this convergence faces substantial challenges, including differences in epistemology, regulatory standards, evidence hierarchies, and practitioner training. Limited clinical trials, quality assurance concerns, and issues related to intellectual property rights and biopiracy further complicate harmonization. Despite these barriers, the World Health Organization’s Traditional Medicine Strategy (2014–2023) and its newly established Global Centre for Traditional Medicine (India) underscore a growing international commitment to evidence-based integration. Opportunities lie in promoting collaborative research, strengthening regulatory frameworks, enhancing digital health platforms for TM documentation, and fostering intercultural dialogue between health systems. If guided ethically and scientifically, integration can improve access to care, reduce treatment costs, and offer personalized health solutions for chronic and lifestyle-related diseases. This review explored global integration models, evaluated emerging challenges, and identified strategies to support an inclusive, pluralistic, and sustainable healthcare future that respects both traditional wisdom and modern science.

Traumatic brain injury (TBI)-associated cognitive impairment is highly prevalent, severely impacting patients’ daily life and social functioning, with its mechanisms incompletely understood. Globally, TBI affects over 69 million people annually, and post-TBI cognitive impairment may last for years, or even a lifetime, imposing heavy burdens on patients’ families. The brain-lymphatic axis (glymphatic + peripheral lymphatic systems, especially meningeal vessels) has gained attention: glymphatic dysfunction (dependent on astrocyte endfeet Aquaporin-4 polarization, key for clearing β-amyloid and other wastes) causes metabolic waste accumulation and neuroinflammation, while peripheral lymphatic stasis worsens cognitive decline. This review aims to summarize their roles, dissect mechanisms, and outline therapies. The review found that most current studies explore the glymphatic system and the peripheral lymphatic system in isolation, lacking understanding of their dynamic interplay (e.g., bidirectional inflammatory factor transmission, immune cell migration, synergistic dysfunction); longitudinal studies that track axis changes across TBI stages (acute, subacute, chronic) are scarce; diagnostic tools are insufficient (non-invasive biomarkers lack large-scale clinical validation, and imaging has limited clinical use); and existing therapeutic strategies mostly target single subsystems, with few combined interventions for the whole axis. In conclusion, this review highlights critical gaps in current knowledge and proposes integrated, axis-targeted approaches as a promising direction for future research and therapeutic development.

Harlequin ichthyosis, one of the rarest and most severe skin disorders, is mainly characterized by extreme hyperkeratosis, severely impairing the natural barrier function of the skin. This congenital disease results from a mutation in the ABCA12 gene responsible for lipid transport, whereby healthy skin development is assured. Harlequin ichthyosis is an autosomal recessive condition that requires parents to carry a defective gene copy for the disorder to manifest in their offspring. Babies born with Harlequin ichthyosis have thick skin plates that crack and flake off; they easily become dehydrated, infected, and may suffer from respiratory complications. With new improvements in neonatal care and systemic therapy, notably retinoid therapy, infants’ survival rates have improved. This review provides an inclusive overview of the pathophysiology, clinical features, diagnostic methods, management, and potential future therapies for Harlequin ichthyosis. In addition, a discussion on genetic counseling and its importance in managing family risk factors is also included, as well as a look into cutting-edge research focused on gene therapy and potential curative treatments.

The association between chronic inflammation and cancer has reshaped our understanding of tumorigenesis and cancer therapy. Inflammatory responses can both promote and suppress cancer, depending on the context and timing. Key molecular players, such as nuclear factor kappa-light-chain-enhancer of activated B cells, interleukin-6, signal transducer and activator of transcription 3, and a variety of immune cell types, including tumor-associated macrophages, myeloid-derived suppressor cells, and regulatory T cells, orchestrate an environment conducive to tumor survival, angiogenesis, metastasis, and immune evasion. In recent years, immunotherapy, particularly immune checkpoint inhibitors, has revolutionized cancer treatment. However, its success varies across tumor types and patients, underscoring the need to understand the tumor microenvironment and inflammatory context. This review examines the mechanistic underpinnings of inflammation-driven cancer, discusses translational research efforts targeting inflammatory pathways, and explores clinical applications, including the integration of immunotherapy with anti-inflammatory agents and biomarkers for personalized treatment. Future directions in the field include the application of artificial intelligence, microbiome research, single-cell technologies, and gene editing tools to further tailor therapies and overcome resistance mechanisms.

The prognostic nutritional index (PNI), calculated from serum albumin and lymphocyte count, reflects a patient’s immune-nutritional status and has been proposed as a prognostic marker in hepatocellular carcinoma (HCC). However, its role in advanced HCC patients treated with atezolizumab plus bevacizumab (Ate/Bev) remains unclear. In this study, we aimed to evaluate the prognostic value of PNI in patients receiving first-line Ate/Bev therapy.

We retrospectively analyzed 362 patients with unresectable HCC who received Ate/Bev between November 2020 and June 2023 across two centers. Based on prior literature, a cutoff of 45 was used to classify patients into low-PNI (<45) and high-PNI (≥45) groups. Propensity score matching was performed to balance baseline characteristics.

After propensity score matching, 130 patients (65 per group) were included in the analysis. The high-PNI group showed a significantly lower incidence of grade ≥ 3 treatment-related adverse events (10.8% vs. 24.6%, p = 0.039), a higher objective response rate (38.4% vs. 20.0%, p = 0.037), and significantly longer overall survival (16.7 vs. 7.9 months, p = 0.009). Although progression-free survival was longer in the high-PNI group (4.8 vs. 3.0 months), the difference was not statistically significant (p = 0.597). Multivariate analysis confirmed that PNI was an independent predictor of overall survival (hazard ratio: 0.574, 95% confidence interval: 0.353–0.933, p = 0.025), after adjusting for vascular invasion, alpha-fetoprotein levels, concurrent therapy, and post-treatment interventions.

PNI is an independent prognostic factor for overall survival in advanced HCC patients treated with Ate/Bev in real-world clinical practice. Incorporating PNI into routine assessments may enhance risk stratification and guide therapeutic decision-making.