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.

Microbial resistance and oxidative stress are two significant health issues associated with chronic illnesses and therapy failures. The antioxidant and antibacterial properties of Euphorbia cuneata Vahl. aerial component extracts made with various polarity solvents were assessed in this work.

Disc diffusion and minimum inhibitory concentration (MIC) tests were used to evaluate the 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity, total phenolic and flavonoid contents, and antimicrobial activity of n-hexane, toluene, ethanolic, and aqueous extracts against specific ESKAPE pathogens (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Candida albicans). High-performance liquid chromatography and gas chromatography-mass spectrometry were used to further characterize the most active extract.

Compared to the aqueous (IC₅₀ = 51.61 µg/mL), toluene (IC₅₀ = 30.57 µg/mL), and n-hexane (IC₅₀ = 128.15 µg/mL) extracts, the ethanolic extract demonstrated the greatest 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity (97.90 ± 0.8%; IC₅₀ = 28.52 µg/mL). Additionally, it has the highest levels of flavonoids (40.5 ± 1.5 mg luteolin equivalents/g) and phenolic (80.0 ± 0.2 mg gallic acid equivalents/g). While gas chromatography-mass spectrometry found methyl 12-hydroxy-9-octadecenoate (44.39%) as the main volatile molecule, high-performance liquid chromatography analysis identified caffeic acid, pyrogallol, rutin, and 7-hydroxyflavone as important ingredients. The ethanolic extract showed antifungal activity against C. albicans (MIC = 6.25 mg/mL) and moderate antibacterial activity with the lowest MIC values against S. aureus (450 µg/mL) and E. coli (500 µg/mL).

The ethanolic extract of Euphorbia cuneata demonstrated potent in vitro antioxidant activity and moderate antimicrobial effects, primarily attributable to its high phenolic and flavonoid content. These results support its potential as a natural source of bioactive compounds for further development.

Colorectal polyp detection from endoscopic images is critical for the early diagnosis of colorectal cancer. However, traditional deep learning methods often suffer from limited generalization when deployed across datasets containing different polyp morphologies. This work aimed to investigate whether vision-language foundation models can facilitate zero-shot generalization across multiple polyp datasets without target-domain fine-tuning.

We introduced a zero-shot colorectal polyp detection framework based on Contrastive Language-Image Pretraining (CLIP) to improve cross-dataset detection performance. Key innovations include: (1) a background patch contrastive loss using pseudo-normal tissue patches to teach the model to distinguish normal mucosa from polyps; (2) attribute-enhanced text prompts that incorporate domain-specific descriptors of polyp appearance, improving the model’s semantic generalization to novel polyp morphologies; and (3) an enhanced CLIP visual adapter with per-layer adaptive feature fusion and generalized mean pooling to capture multi-scale features for better polyp localization. During training, we use one annotated colorectal polyp dataset (e.g., CVC-ColonDB) to learn patch-level image-text correspondence. The model is then evaluated in a zero-shot manner on different polyp datasets (CVC-ClinicDB, Kvasir-SEG, and CVC-300), where we evaluate pixel-level anomaly detection performance.

The framework demonstrated robust zero-shot generalization on unseen test cohorts. Without any dataset-specific fine-tuning, the model achieved a mean pixel-level AUROC of 0.94 and a mean average precision of 0.81 across the 12 leave-one-dataset-out zero-shot transfer settings. In the CVC-ColonDB-source benchmark, the model achieved a mean Dice coefficient of 0.84 across CVC-ClinicDB, Kvasir-SEG, and CVC-300. This high level of performance was consistent across datasets with distinct visual characteristics, underscoring the ability of the model to detect diverse polyp morphologies that it had not been explicitly trained to recognize.

Our findings demonstrate that an anomaly-aware vision-language model significantly improves cross-dataset polyp detection generalization without requiring normal images for training. This multimodal strategy may facilitate the robust deployment of artificial intelligence-based colorectal screening systems by enabling reliable detection of diverse polyp morphologies across different clinical settings. Extension to non-polyp colorectal pathologies (e.g., ulcerative colitis and colorectal tumors) remains an important direction for future work, pending the availability of pixel-level annotated datasets for these lesion categories.

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.

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.

Myelodysplastic syndromes (MDS) are a group of hematopoietic disorders characterized by ineffective hematopoiesis, with manifestations of cytopenias in one, two, or three lineages. CD34+ micromegakaryocytes and giant platelets are very rarely seen in MDS patients but may lead to unnecessary treatments. Therefore, we report and follow up on an MDS case with such an unusual finding.

A 57-year-old male veteran with a history of MDS, alcoholic cirrhosis, and portal hypertension presented to the Emergency Department in 2020 for evaluation after a blackout, at which time peripheral blood samples and bone marrow biopsies were obtained. Flow cytometry analysis of his peripheral blood detected 8% CD34+ cells. This finding raised the possibility of acute leukemic transformation from MDS. Further studies revealed that these CD34+ cells represented dysplastic micromegakaryocytes and giant platelets rather than blasts. During his 4-year follow-up, the patient was alive and complained only of easy fatigability, lasting several weeks. His laboratory results showed pancytopenia and persistent iron-deficiency anemia.

The distinction between micromegakaryocytes and giant platelets versus megakaryoblasts is extremely important in patients with MDS. This distinction may prevent misdiagnosis of acute leukemia and unnecessary treatments such as chemotherapy.

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.

Hepatitis B virus (HBV) infection and hepatitis C virus (HCV) infection are among the leading causes of chronic liver diseases worldwide. Through the same transmission routes, HBV/HCV coinfection is widespread and aggravates liver damage. In this study, we aimed to assess the safety and efficacy of sofosbuvir/velpatasvir (SOF/VEL) and the pre-treatment of tenofovir alafenamide fumarate (TAF) on HBV reactivation in HBV/HCV coinfected patients.

A multicenter, prospective, single-arm, open-label 12-week trial, followed by a 12/48-week observational clinical trial, was conducted. Ninety-six adults with chronic HBV/HCV coinfection were enrolled from May 2021 to December 2024 in thirteen centers in China. Seventy-seven non-cirrhotic patients were included in Group 1 and nineteen compensated cirrhotic patients in Group 2. All subjects were enrolled to receive SOF/VEL once daily for 12 weeks. Non-cirrhotic subjects received TAF once daily for 28 weeks, and compensated cirrhotic subjects received TAF once daily for 64 weeks simultaneously. Statistical significance was set at P < 0.05.

At the end of SOF/VEL treatment, the overall sustained virologic response was 97.9%, of which 100% was achieved in Group 2. HCV RNA, HBV DNA, and HBV RNA levels were substantially decreased in all patients. Alanine aminotransferase (ALT) (61.5 vs. 21.9, P < 0.001) and aspartate aminotransferase (AST) (50.8 vs. 25.7, P < 0.001) levels decreased, and albumin (ALB) (42.4 vs. 45.1, P < 0.001) level increased compared to pre-treatment in Group 1 at 12 weeks post-treatment. ALT (64.1 vs. 25.2, P < 0.001), AST (65.7 vs. 29.7, P < 0.001), alkaline phosphatase (ALP) (111.6 vs. 88.2, P < 0.05), and alpha-fetoprotein (AFP) (17.9 vs. 4.7, P < 0.05) levels decreased, and ALB (41.3 vs. 42.5, P = 0.051) and platelet count (PLT) (114.0 vs. 127.2, P = 0.052) levels showed a trend toward increase compared to pre-treatment in Group 2 at 48 weeks post-treatment. Liver stiffness measurement (LSM) (22.6 vs. 12.7, P < 0.01), aspartate aminotransferase to platelet ratio index (APRI) (1.6 vs. 0.6, P < 0.001), and fibrosis-4 index (FIB-4) (4.7 vs. 2.6, P < 0.05) significantly decreased after treatment in Group 2. Two patients in Group 1 with genotype 3 showed HBV reactivation and HCV relapse, respectively. No drug-related adverse events were observed in the study.

SOF/VEL effectively achieves a sustained virologic response and improves liver function, with an acceptable safety profile in chronic HBV/HCV coinfected patients, including those with compensated cirrhosis, who achieved modest improvement in non-invasive fibrosis indices. Pre-administration of TAF may mitigates the risk of HBV reactivation in this population.

Luteolin is a dietary flavonoid widely distributed in fruits and vegetables. It has attracted substantial preclinical interest due to its pleiotropic hepatoprotective effects against hepatic steatosis, inflammation, fibrosis, and hepatocellular carcinoma. By reviewing data from in vitro and in vivo studies, this review comprehensively synthesizes the full spectrum of liver-directed pharmacology of luteolin, covering metabolic and toxic liver injury, fibrosis, cancer, and viral hepatitis, while critically mapping each mechanism to specific disease contexts and systematically identifying the key challenges limiting its clinical translation. The underlying mechanisms of luteolin action involve activation of Nrf2-mediated antioxidant defense, suppression of NF-κB- and NLRP3-driven inflammatory responses, inhibition of hepatic stellate cell activation via the TGF-β/Smad and STAT3 pathways, and regulation of metabolic homeostasis through liver X receptor (LXR)/SREBP-1c and AMPK signaling. Despite well-characterized mechanisms in preclinical models, several critical gaps hinder its clinical translation: (1) Rigorous randomized controlled trials in well-defined patient populations are scarce, with only one combination supplement study reported. (2) The relative contribution of luteolin metabolites to its overall bioactivity remains poorly understood, even though derivatives such as luteolin-7-diglucuronide exhibit distinct pharmacological properties. Cell-type-specific delivery systems, which show promise in preclinical fibrosis and cancer models, have not been evaluated clinically. (3) Systematic studies on the synergistic effects of luteolin with standard-of-care drugs remain largely exploratory. Overall, luteolin is a promising multi-target nutraceutical for liver diseases, and its clinical translation requires optimized delivery strategies, investigation of metabolite activity, and well-designed human clinical trials.