Hepatocellular carcinoma (HCC) is characterized by high mortality, frequent recurrence, and limited long-term benefit from systemic therapy and radiotherapy. Circular RNAs (circRNAs), a class of covalently closed non-coding RNAs with high molecular stability and tissue-specific expression, have emerged as important regulators of HCC biology and treatment response. We searched PubMed from database inception to May 2, 2026 and manually screened the reference lists of eligible studies and relevant reviews for studies investigating circRNA-related molecular mechanisms, tumor progression, therapeutic resistance, radiotherapy response, or translational applications in HCC. A total of 694 records were identified in PubMed, 694 records were screened after duplicate removal, and 42 studies were included in the qualitative synthesis. Original studies involving human tissues, clinical cohorts, cell lines, or animal models were eligible. Title/abstract screening, full-text assessment, and data extraction were performed independently by two reviewers, with disagreements resolved by consensus or senior-author adjudication. Given substantial heterogeneity in study design, model systems, molecular endpoints, and reported outcomes, findings were synthesized qualitatively rather than by meta-analysis, and a structured qualitative evidence appraisal was used to weight mechanistic and translational conclusions. The included evidence indicates that circRNAs participate in HCC progression through miRNA sponging, RNA-binding protein interactions, transcriptional regulation, epigenetic modulation, and, in selected contexts, translational activity. Distinct oncogenic and tumor-suppressive circRNAs converge on pathways related to proliferation, epithelial-mesenchymal transition, metastasis, ferroptosis, stemness, and DNA-damage repair. CircRNAs were also associated with sorafenib and lenvatinib response, radioresistance, and radiosensitivity. Emerging translational applications include tissue and liquid-biopsy biomarkers, especially exosomal circRNAs, as well as junction-targeted oligonucleotide strategies. Current evidence supports circRNAs as mechanistically relevant regulators and promising translational candidates in HCC. However, progress toward clinical application is constrained by etiologic heterogeneity, limited standardization, incomplete specificity validation for therapeutic targeting, and the lack of multicenter prospective validation studies.

Guinea has the highest incidence of hepatocellular carcinoma (HCC) in Sub-Saharan Africa (> 21 cases/100,000 habitants/year). This high incidence is largely attributed to the combination of a high prevalence of chronic hepatitis B virus (HBV) infection and significant exposure to aflatoxin B1 (AFB1), a known carcinogen. However, the clinical presentation of HCC in Guinea has not been well-documented to date. We conducted a retrospective analysis of 216 HCC cases from patients who received care between 2015 and 2023 at the Donka University Hospital in Conakry, the main tertiary care institution of the country. Demographical, clinical, and biological data were extracted from medical records and analyzed using both descriptive and inferential statistics. The median age of patients was relatively young, at 43.0 years (IQR = 34.5-55.0) with a male-to-female ratio of 3.1 (162/54). Half of the male patients were younger than 41 years. Chronic HBV infection was the predominant risk factor accounting for 75.0% of cases. Almost all patients have been exposed to HBV at some moment of their lives (total anti-HBc seropositivity: 92.2%). Chronic HBV infection was rarely replicative with only 7.8% of patients tested positive for HBeAg. Hepatitis C virus Infection was observed in a small subset of cases (7.9%). Toxic risk factors such as alcohol (12.5%) or tobacco (19.4%) were also rather infrequent. HBV-infected patients were significantly younger than non-HBV patients (median age: 40.0 vs. 50.5 years, p = 0.0109). Susu ethnicity, a Mande-speaking group primarily residing in Guinea's coastal plain was associated with an earlier onset of HCC than other ethnic groups (median age: 37.0 vs. 46.0 years, p = 0.0007). HBV infection is the major risk factor of HCC in Guinea with an earlier onset of the disease by nearly a decade compared to other risk factors. A notable ethnic variation was observed with Susu patients displaying a predisposition to early HCC. Further molecular research is needed to precisely assess the potential role of AFB1 in liver carcinogenesis of Guinean populations.

Hepatic steatosis is a precursor to metabolic dysfunction-associated steatohepatitis (MASH), which is linked to obesity and diabetes and poses a risk for liver cirrhosis and cancer. For detecting MASH and hepatic steatosis, liver biopsy is the reference method, but it is invasive and impractical for repeated monitoring of treatment efficacy. Our goal was to develop a convenient and non-invasive tool for accurately identifying MASH and steatosis grade in people with obesity. This retrospective study included 321 people with obesity who underwent bariatric surgery, during which liver biopsies were also performed. Clinical characteristics, presurgical computed tomography (CT)-derived parameters, magnetic resonance imaging proton density fat fraction (MRI-PDFF), and CT-based skeletal muscle index (SMI) were obtained. A convenient model consisting of liver CT attenuation value (CTLiver), alanine aminotransferase (ALT) and high-density lipoprotein cholesterol (HDL-C) was developed for identifying MASH, with area under the curve (AUC) of 0.799. To predict hepatic steatosis of grade ≥ 1, ≥ 2 and 3, the AUCs of CTLiver-based combination models were 0.954, 0.927, and 0.894, respectively. The diagnostic performance of the CTLiver-based combination models was comparable to that of liver MRI-PDFF in identifying different hepatic steatosis grades (Delong's test, p > 0.05). CT-based SMI was significantly positively correlated with hepatic steatosis grade (r = 0.12, p = 0.031) and non-alcoholic fatty liver disease (NAFLD) activity score (r = 0.18, p = 0.002). The liver CT-based composite biomarkers can identify MASH and hepatic steatosis grade with high diagnostic performance in people with obesity, providing a non-invasive, accessible, and practical supplementary tool for clinical stratified management.

Double balloon enteroscopy (DBE) is a key diagnostic and therapeutic tool for small bowel pathologies, particularly in patients with obscure gastrointestinal bleeding (OGIB). Although DBE's diagnostic value is well established, long-term quantitative data on hemoglobin recovery and transfusion needs remain limited. To evaluate the effectiveness of DBE and endoscopic intervention in improving hemoglobin levels and reducing transfusion and iron supplementation requirements in patients with OGIB. We conducted a retrospective cohort study at Rambam Medical Center between January 2014 and June 2023, including 77 adults who underwent 96 DBE procedures. Data were collected from electronic medical records and community health centers, with follow-up of up to 5years. The primary endpoint was an increase in hemoglobin of ≥ 2g/dL or > 9g/dL at ≥ 6months post-procedure. Secondary outcomes included blood transfusion requirements, intravenous iron supplementation, repeat enteroscopy, and surgery. Angioectasias were the most common lesions (42%). Therapeutic endoscopic intervention was performed in 51% of patients, most commonly argon plasma coagulation (72%). The mean follow-up duration was 3.6years. Overall, mean hemoglobin increased from approximately 9g/dL pre-procedure to 11.5g/dL at last follow-up, with 52% achieving a ≥ 2g/dL rise and 79% attaining hemoglobin > 9g/dL. Compared with diagnostic-only DBE, patients undergoing intervention were older (72 vs 64years, p = 0.003), had lower baseline hemoglobin (8.35 vs 9.59g/dL, p = 0.009), and higher prior transfusion rates (62% vs 37%, p = 0.041). At follow-up, they had lower mean hemoglobin (10.62 vs 12.41g/dL, p = 0.001) and required more transfusions (38% vs 11%, p = 0.007). Fewer intervention patients achieved hemoglobin > 9g/dL (69% vs 89%, p = 0.047), while the proportion achieving a ≥ 2g/dL rise was similar (46% vs 58%). Outcomes were comparable between overt and occult bleeding. Patients undergoing DBE without prior VCE required significantly more pre-procedure transfusions (87% vs. 40%, p = 0.001) and had less favorable outcomes, including a lower proportion achieving hemoglobin > 9g/dL at follow-up (53% vs 85%, p = 0.011). Among patients with negative DBE but prior VCE (n = 22), VCE frequently identified lesions-most commonly angioectasias (45%), followed by ulcers (27%) and polyps (14%). Patients requiring therapeutic DBE appear to represent a higher-risk population with more severe baseline anemia and ongoing transfusion needs. These findings suggest that combined endoscopic management and adjunctive medical therapy may be necessary in complex small-bowel bleeding. Prospective studies are needed to clarify the impact of DBE-directed therapy on long-term clinical outcomes.

Crohn's disease (CD) exhibits substantial heterogeneity in disease behavior and therapeutic outcomes across distinct disease locations. Specific alterations in the gut microbiota and metabolites may drive this variation. This review aims to characterize the distinctive microbial and metabolic signatures across CD phenotypes based on disease location. Electronic databases were searched from inception to December 2025 for studies that observed alterations in gut microbiota and metabolites in CD patients with different disease locations. Forty-eight studies including 3,577 CD patients and 2,916 healthy controls (HCs) were analyzed. Ileal Crohn's disease (ICD) was characterized by significant dysbiosis compared with HCs, featuring enrichment of Enterobacteriaceae (especially adherent-invasive Escherichia coli [AIEC]), Fusobacterium and Shigella, alongside depletion of Faecalibacterium prausnitzii, Roseburia and Coprococcus. Patients with colonic Crohn's disease (CCD) exhibited increased levels of Proteobacteria, pro-inflammatory families (Actinomycetaceae, Micrococcaceae) and opportunistic pathogens (Streptococcus, Klebsiella). In contrast, a decrease in short-chain fatty acid (SCFA)-producing families (Lachnospiraceae, Ruminococcaceae) and F. prausnitzii was observed in CCD. Ileocolonic Crohn's disease (ICCD) displayed features combining ICD and CCD elements, with specific depletion in Alistipes communis and enrichment of Shigella flexneri. More pro-inflammatory bacteria were observed in ICD compared with CCD. In terms of metabolic alterations, ICD showed impaired enterohepatic bile acid circulation with excessive fecal loss of conjugated bile acids, while CCD exhibited defective conversion of primary to secondary bile acids. ICCD exhibited both impaired ileal reabsorption and defective colonic transformation. Our results identified disease location-specific alterations in the microbiome and metabolome of CD, which might be associated with the clinical manifestations and prognosis of different phenotypes.

To compare urban-rural disparities in overall survival of patients with esophageal squamous cell carcinoma (ESCC) in China and identify independent prognostic factors. A retrospective cohort study including 133,064 ESCC patients diagnosed between 1973 and 2024 was conducted. Survival curves were estimated using the Kaplan-Meier method, and differences were tested by log-rank test. Univariate and multivariate Cox regression analyses were performed to identify prognostic factors. Propensity score matching (PSM) was applied to balance baseline characteristics between rural and urban groups. Overall survival was significantly better in rural patients than in urban patients (log-rank P < 0.001). Multivariate analysis showed that urban residence was an independent risk factor for poor prognosis (HR = 1.032, 95% CI: 1.001-1.064, P = 0.042). Significant urban-rural differences were observed in age, gender, smoking, alcohol intake, tumor differentiation, TNM stage, and treatment modality. Subgroup analysis revealed that the survival advantage of rural patients was more prominent in stage Ⅲ-Ⅳ disease. After 1:1 PSM, survival differences between urban and rural patients were no longer significant (P = 0.375). Rural residence is an independent favorable prognostic factor for ESCC, and its effect is mainly mediated by baseline clinicopathological characteristics, lifestyle factors, and treatment patterns. After adjusting for confounding factors, survival between urban and rural patients becomes comparable. These findings provide real-world evidence for risk stratification and individualized treatment of ESCC. Future studies are needed to explore the molecular mechanisms underlying urban-rural heterogeneity in ESCC.

Endoscopic submucosal dissection (ESD) is a cornerstone organ-preserving treatment for colorectal neoplasia; however, the impact of advanced age on procedural efficiency, safety, and economic burden remains controversial. This study aimed to comprehensively evaluate these outcomes in older adults within a real-world clinical setting. We retrospectively reviewed 255 patients who underwent colorectal ESD between January 2022 and December 2023. Patients were divided into elderly (≥ 65 years, n = 119) and non-elderly (< 65 years, n = 136) groups. Operative outcomes (resection and wound-management speeds), safety (delayed bleeding and perforation), and economic metrics (hospital stay and costs) were evaluated. Multivariable regression, age-stratified models, and 1:1 propensity score matching (PSM) were utilized to rigorously adjust for baseline confounders. Elderly patients presented with significantly larger and morphologically more complex lesions. Nevertheless, multivariable analyses demonstrated no significant independent association between age and resection speed or wound-management speed, which was fully supported by subsequent PSM and restricted cubic spline (RCS) analyses. Complication rates were extremely low (2.0% for bleeding, 0.8% for perforation) with no descriptive differences between groups. Although initial regression models suggested a slight age-related increase in hospital costs and length of stay, these economic disparities were attenuated and lost significance after applying PSM to balance clinical drivers such as ASA physical status and anesthesia methods (matched hospital costs: 11.39k vs. 10.57k RMB, p = 0.249; identical median stay: 4 vs. 4 days). Appropriately selected elderly patients achieve operative and safety outcomes comparable to younger individuals during colorectal ESD. The initial economic variances observed are likely driven by underlying comorbidities and anesthetic requirements rather than chronological age itself. Clinical decisions should prioritize comprehensive, patient-centered assessments over strict age cutoffs.

Conventional non-invasive tests (NITs) for chronic liver disease (CLD) conflate fibrosis and inflammation, limiting diagnostic accuracy. We aimed to redefine the pathophysiological basis of key biomarkers and translate these insights into an integrated diagnostic strategy. In a critically underpowered retrospective cohort of 99 patients with histologically confirmed CLD, we performed a comprehensive evaluation of FIB-4, MRE, and DHR-MAP. Analytical rigor was ensured through post-hoc power assessment and stringent multiple comparisons correction. Statistical approaches included partial correlation, hierarchical regression, and mediation analysis to establish biomarker specificity. Diagnostic performance and the proposed two-step strategy were validated via 5-fold cross-validation. Our analysis resolved a fundamental biomarker paradox. FIB-4 was identified as a marker predominantly reflective of inflammatory activity, showing no independent association with fibrosis after controlling for hepatitis (p=0.414). Conversely, MRE and DHR-MAP were established as fibrosis-specific indicators. This mechanistic clarity informed a novel two-step diagnostic framework: For advanced fibrosis (≥F3), initial screening with DHR-MAP+FIB-4 achieved high sensitivity (0.778 in cross-validation), followed by confirmatory MRE providing high specificity (1.000). For moderate hepatitis (≥G2), FIB-4 screening delivered perfect sensitivity (1.000), with subsequent DHR-MAP+FIB-4 confirmation offering balanced accuracy (specificity 0.857). This integrated strategy substantially reduced diagnostic errors compared to single-modality approaches (88.5% net error reduction for fibrosis; 30.4% for hepatitis) in this cohort, although performance metrics require validation in larger, prospectively designed studies. This study provides a pathophysiological redefinition of key CLD biomarkers, proposing FIB-4 as an inflammation-predominant marker and introducing a novel two-step diagnostic framework that strategically sequences biomarkers based on their specific strengths. The findings-particularly the dissociation of FIB-4 from fibrosis-offer a mechanistic hypothesis and a practical diagnostic template that must be validated in larger, appropriately powered prospective cohorts to assess generalizability and clinical impact.