The intestinal barrier, a critical interface between the body and the external environment, is essential for maintaining internal homeostasis. Comprising mechanical, chemical, immune, and biological components, its dysfunction underpins multiple gastrointestinal pathologies. Circular RNAs (circRNAs), covalently closed non-coding RNAs, have emerged as central regulators of gut barrier homeostasis. This review synthesizes advances in circRNA roles in intestinal stem cell renewal, apoptosis-proliferation balance, microbiome interactions, and immune regulation. Key findings highlight circRNA networks operating via competitive endogenous RNA mechanisms, protein interactions, and translational potential to influence barrier function. We further discuss circRNAs as diagnostic biomarkers in inflammatory bowel disease and their therapeutic potential in barrier-related pathologies. Advances in RNA nanotechnology (e.g., lipid nanoparticles) and synthetic biology position engineered circRNAs as next-generation therapies for precision intervention in gastrointestinal disorders. Importantly, this review also critically examines the current limitations of these translational approaches, including delivery challenges, safety considerations, and the preliminary nature of many preclinical findings, providing a balanced perspective on the path from bench to bedside.

Adeno-associated virus (AAV) vectors have favorable safety and durable transgene expression but are limited in oncology by insufficient tumor specificity and off-target expression. Tumor hypoxia and non-small cell lung cancer (NSCLC)-associated surface ligands offer complementary layers of biological selectivity for more precise gene delivery. This study proposes an NSCLC-directed, hypoxia-responsive AAV architecture that integrates MGS4-guided capsid targeting with dual hypoxia-responsive element (HRE)-gated promoters driving glutamine-modified C-X-C motif chemokine ligand 9-fragment crystallizable region fusion protein (Q-CXCL9-Fc) expression and baculoviral IAP repeat containing 5 (BIRC5)-linked mesothelin (MSLN) silencing. We conceptually designed an AAV vector that combines three layers of NSCLC selectivity: MGS4-guided capsid targeting, hypoxia-gated transcription, and tumor-active promoter control. The capsid displays the MGS4 peptide, isolated by phage display biopanning as a high-affinity ligand for the lung squamous cell carcinoma cell line HCC15 and later shown to internalize into a substantial fraction of NSCLC cell lines and bind a subset of human NSCLC biopsy samples, indicating activity across multiple NSCLC subtypes. The genome encodes Q-CXCL9-Fc under a 4× HRE-cytomegalovirus promoter to sustain C-X-C motif chemokine receptor 3-dependent T-cell recruitment and a miR-30-based short hairpin RNA targeting MSLN under a 4× HRE-BIRC5 promoter to inhibit tumor progression. This architecture is hypothesized to enrich AAV entry into NSCLC lesions via MGS4 while restricting Q-CXCL9-Fc secretion and MSLN silencing to hypoxic, BIRC5-active tumor regions, enabling synergistic enhancement of antitumor immunity and suppression of tumor-intrinsic pathways. The proposed multimodal, hypoxia-responsive AAV platform represents a conceptual precision oncology strategy that couples environmental sensing, tumor-specific transcription, and peptide-defined tropism within a single vector and could inform next-generation NSCLC-directed AAV systems.

Medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy arising from parafollicular C-cells with known variations in cytomorphologic and immunophenotypic features. New neuroendocrine markers pituitary homeobox 2 (PITX2), paired-like homeobox 2B (PHOX2B), and heart and neural crest derivatives expressed 2 (HAND2) have recently been introduced, but studies using these markers in MTC are limited. The aim of this study was to evaluate the expression and potential diagnostic utility of PITX2, PHOX2B, and HAND2 in primary and secondary MTCs and to compare their expression with chromogranin A, synaptophysin, insulinoma-associated protein 1 (INSM1), and calcitonin.

A total of 34 histologically confirmed cases of MTC with available cell blocks were included. Sixteen MTC samples were fine-needle aspirates from primary thyroid lesions, and eighteen were from secondary metastatic lesions. Twelve samples from thyroid carcinomas of follicular origin were included as controls.

PITX2 positivity was observed in 17 (50.0%) MTC samples and in 4 (33.3%) control samples (P = 0.502). PITX2 positivity was found in 43.8% of primary thyroid MTC lesions and in 55.6% of secondary MTC lesions (P = 0.366). Co-expression of PITX2 with chromogranin A, synaptophysin, INSM1, and calcitonin was observed. PHOX2B and HAND2 were negative in all MTC and control samples.

There were no significant differences in PITX2 expression between primary and secondary MTC samples. PITX2 did not show reliable utility in distinguishing MTC from thyroid carcinomas of follicular origin. PHOX2B and HAND2 were negative in all samples. These results suggest that these new markers do not offer diagnostic value for MTC as stand-alone markers or as additions to the diagnostic workup panel.

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.

Liver fibrosis is a central pathological process driving the progression of chronic liver disease, yet effective antifibrotic therapies remain limited. Increasing evidence has identified the mineralocorticoid receptor (MR), a ligand-activated nuclear receptor, as a key regulator of intrahepatic homeostasis and fibrogenesis. MR is expressed across multiple hepatic cell types, including hepatocytes, hepatic stellate cells, macrophages, and liver sinusoidal endothelial cells, where it integrates metabolic, inflammatory, and microvascular signaling. Under pathological conditions, MR activation—mediated by both aldosterone-dependent and ligand-independent mechanisms such as hypoxia and oxidative stress—amplifies core profibrotic pathways, including transforming growth factor-β (TGF-β) signaling, reactive oxygen species (ROS) generation, and nuclear factor-kappa B (NF-κB)–driven inflammation. These molecular mechanisms are executed in a cell-type–specific manner, promoting hepatic stellate cell activation, macrophage-mediated inflammation, hepatocyte metabolic dysfunction, and liver sinusoidal endothelial cell capillarization, thereby forming a self-reinforcing fibrogenic network. Preclinical studies consistently demonstrate that mineralocorticoid receptor antagonists attenuate fibrosis by targeting these interconnected pathways. However, clinical evidence remains limited, with only early-phase trials in metabolic dysfunction-associated steatohepatitis and indirect support from cardiorenal studies. Nonsteroidal mineralocorticoid receptor antagonists, particularly finerenone, exhibit improved receptor selectivity and safety profiles, highlighting their therapeutic potential. Future research should focus on disease-specific patient stratification, validated antifibrotic endpoints, and rigorous safety evaluation to enable effective clinical translation of MR-targeted therapies in liver fibrosis.

The Asia-Pacific region accounts for a larger share of the hepatitis B burden than any other regions of the world, presenting a challenge to meeting the World Health Organization (WHO) 2030 elimination targets. In this study, we aimed to quantify the burden of chronic hepatitis B (CHB) and project its trends through 2030 using the Global Burden of Disease 2023 framework, thereby identifying gaps and priorities for the Asia-Pacific region to achieve WHO 2030 targets.

Using data from the Global Burden of Disease Study 2023, we analyzed CHB prevalence, mortality, and disability-adjusted life years. We evaluated temporal trends (1990–2023) using average annual percent changes and projected the 2024–2030 burden using Bayesian age-period-cohort models.

In 2023, the Asia-Pacific region accounted for 63% of global CHB cases (178.0 million), 66% of deaths (259.1 thousand), and 65% of disability-adjusted life years (8.4 million). Regional prevalence and mortality rates exceeded global averages, although childhood (<5 years) prevalence was comparatively lower (590.3 vs. 1,325.3 per 100,000). East Asia bore the highest absolute burden (99.2 million cases), and South Asia had the largest pediatric caseload. Between 1990 and 2023, Western Asia showed the steepest decline in adult prevalence (−1.99%), whereas Southeast and Central Asia exhibited upward mortality trends. Projections indicate that the Asia-Pacific region is off track to meet the WHO 2030 disease elimination targets, as the prevalence rate in children under five years remains above the 0.1% target threshold and absolute mortality is projected to increase.

The Asia-Pacific region continues to contribute the largest share of the global CHB burden and now faces persistent gaps despite progress. Although substantial progress has been made in reducing prevalence through immunization, the region is currently off track to meet the WHO 2030 targets for both incidence and mortality.

Studies suggest that Yiguanjian (YGJ) may exert a therapeutic effect on liver fibrosis. However, the active components and molecular targets responsible for its action remain unclear. This study aimed to systematically evaluate the active ingredients and potential targets of YGJ in the treatment of liver fibrosis.

Active compounds and corresponding targets of YGJ were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the Encyclopedia of Traditional Chinese Medicine (ETCM) databases. Liver fibrosis-related datasets were obtained from the Gene Expression Omnibus (GEO) database and divided into training and validation sets. Differentially expressed genes (DEGs) from the training set were subsequently analyzed using network pharmacology, molecular dynamics simulations, and immune infiltration analysis. Three machine learning models were employed to screen for core targets, followed by Gene Set Enrichment Analysis (GSEA) and Mendelian randomization (MR) analysis. The validation set was used to assess the expression levels and diagnostic potential of core targets.

A total of 2,887 liver fibrosis-related targets and 1,198 YGJ-related targets were identified. Three hundred and three putative targets for YGJ in the treatment of liver fibrosis were identified. Three machine learning methods further narrowed these down to five core targets. Immune infiltration analysis revealed an increase in effector B cells, resting CD4+ memory T cells, γδ T cells, and M1 macrophages during liver fibrosis progression. MR analysis showed that all five core targets (FABP4, MDM2, AKR1B1, PDGFRB, and NR1H4) had odds ratios greater than 1, indicating that they function as risk factors. Expression analyses in both the training and validation sets consistently validated the MR results, demonstrating strong diagnostic potential. GSEA revealed that the core targets were enriched in key signaling pathways, including Wnt, PPAR, and MAPK. Molecular docking and molecular dynamics simulations showed that the active compounds of YGJ exhibited strong binding affinity and stability with the core targets.

YGJ exerts its potential antifibrotic effects by downregulating or antagonizing the risk-associated targets (FABP4, MDM2, AKR1B1, PDGFRB, and NR1H4). These findings provide new insights into the potential of YGJ for treating liver fibrosis, while offering a scientific reference for the prevention and treatment of chronic liver diseases.

Pancreatic solid tumors encompass diverse pathological subtypes. Objective, accurate, and comprehensive imaging examinations and diagnostic reports are essential for preoperative staging, treatment planning, and prognostic evaluation. Currently, China lacks corresponding guidelines or consensus documents, leading to prominent issues including subjective diagnostic reports, incomplete descriptions, and inconsistent terminology. The present guideline was developed to standardize diagnostic imaging reporting of pancreatic solid tumors in China. Relevant domestic and international evidence on imaging examination techniques, key reporting elements, and diagnostic criteria was systematically reviewed and synthesized. This guideline was developed by a multidisciplinary expert panel through systematic evidence retrieval and appraisal, GRADE-based recommendation grading, modified Delphi consensus, and external review. A total of 20 evidence-based recommendations, 13 strong and 7 weak, were formulated, in aspects of imaging examination and diagnostic reporting standards, including the measurement of the tumor size of pancreatic solid tumors, assessment of the obstruction of the main pancreatic duct and common bile duct, definition, assessment, and clinical significance of pancreatic parenchymal atrophy, the assessment of obstructive acute pancreatitis, pseudocysts/retention cysts, and peripancreatic vessels, criteria for resectability, regional lymph node assessment, criteria for suspicious lymph nodes and descriptions of their specific location, and detection of hepatic and peritoneal metastases. Implementation of this guideline in clinical practice will help standardize the accuracy and consistency of diagnostic imaging reports for pancreatic solid tumors in China, thereby advancing standardized imaging diagnosis and informing clinical treatment decisions.

Nonalcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder with a complex pathogenesis. Although epitranscriptomic modifications such as N6-methyladenosine (m6A) have been implicated in NAFLD, the role of N1-methyladenosine (m1A) and its regulators is largely unexplored. Recently, YTHDF1, a well-characterized m6A reader, was also shown to recognize m1A; however, the functional consequences of this dual specificity are unknown. This study aimed to investigate the role of YTHDF1 in NAFLD pathogenesis and to explore whether its function is mediated through recognition of RNA methylation modification on specific target mRNAs.

Expression of YTHDF1 in NAFLD was analyzed in the GEO database. Loss-of-function studies for YTHDF1 were conducted in vivo (high-fat diet-fed mice) and in vitro (free fatty acid-treated HepG2 cells) in models of NAFLD. We employed RNA-seq and m1A-MeRIP-seq to identify key targets, followed by mechanistic validation of the YTHDF1–m1A–NUPR1 axis using biochemical, histological, and mRNA stability assays.

We identified a critical role for YTHDF1 in promoting hepatic steatosis. NUPR1, a stress-induced transcriptional regulator, undergoes m1A modification. YTHDF1 directly binds to m1A-modified NUPR1 mRNA, enhancing its stability, thereby leading to elevated NUPR1 protein levels. Functionally, upregulated NUPR1 acts as a core driver of NAFLD pathogenesis by activating lipogenic and suppressing fatty acid β-oxidation genes, thereby exacerbating hepatic lipid accumulation.

Our study unveils a novel epitranscriptomic mechanism in which YTHDF1, functioning as a dual-specificity reader, governs NAFLD progression through the m1A-NUPR1 axis. This not only expands the understanding of RNA modification recognition but also establishes the YTHDF1–m1A–NUPR1 pathway as a promising therapeutic target for metabolic liver disease.