Hereditary unconjugated hyperbilirubinemia is most often caused by UGT1A1 mutations and includes Gilbert syndrome, Crigler-Najjar syndrome types I and II, and prolonged neonatal unconjugated hyperbilirubinemia. In Chinese patients, however, the variant spectrum and its clinical relevance remain incompletely characterized. We therefore aimed to define the UGT1A1 variant profile and assess genotype-phenotype correlations in a Chinese cohort.

We retrospectively analyzed 163 patients from the Affiliated Hospital of Hangzhou Normal University (2016–2025). Sanger sequencing of UGT1A1 was performed, covering the enhancer, promoter, and all coding regions. The association between variant types and total serum bilirubin levels was evaluated.

UGT1A1 variants were detected in 156 patients (95.7%), covering 19 distinct variants, including two previously unreported candidate variants (c.272C>G and c.556delinsAATGG). The most common alleles were c.-3279T>G (allele frequency: 0.68), (TA)6>(TA)7 (0.49), and p.G71R (0.23). Coding-region variants were observed more frequently in the Crigler-Najjar syndrome type II group than in the Gilbert syndrome group (P < 0.05), while total bilirubin levels were higher with both coding and non-coding variants than with non-coding variants alone (adjusted P < 0.05 by Dunn’s test), although median-regression confidence intervals included zero.

UGT1A1 genotyping yields a variant detection rate of 95.7% and identifies two previously unreported candidate variants in this Chinese cohort. Exploratory analyses suggest higher bilirubin levels in patients carrying both coding and non-coding variants than in those carrying non-coding variants alone, warranting confirmation in larger cohorts.

Acute decompensation (AD) of cirrhosis has heterogeneous outcomes; existing scores incompletely capture the immune-metabolic mechanisms associated with progression to acute-on-chronic liver failure (ACLF). We aimed to construct and evaluate three latent immune-metabolic dimensions (hyperinflammation, immunoparalysis, and defense-reserve depletion), identify exploratory unsupervised phenotypes, and assess their incremental predictive value beyond The Model for End-Stage Liver Disease (MELD) and Chronic Liver Failure Consortium Acute Decompensation (CLIF-C AD) scores.

In this ambispective cohort study, 485 prospectively enrolled patients formed the discovery cohort (January 2024–September 2025), and 623 patients formed the same-center historical evaluation cohort (December 2019–December 2023). Eleven biomarkers were modeled via exploratory and confirmatory factor analysis. Gaussian mixture modeling identified three phenotypes. Tiered models were compared using Fine-Gray regression and competing-risk-aware performance measures for 90-day ACLF (primary endpoint), and Cox regression and survival performance measures for 90-day mortality.

In the historical evaluation cohort, all three dimensions were independently associated with 90-day ACLF and mortality; immunoparalysis was most strongly associated with ACLF (subdistribution hazard ratio 1.92 per 1 standard deviation [SD], 95% confidence interval [CI] 1.56–2.35; P < 0.001). The Depleted phenotype (P3, approximately 5%) had 90-day ACLF cumulative incidences of 56.0% (discovery) and 66.7% (historical evaluation). In the historical evaluation cohort, FS2-MELD achieved an area under the curve (AUC) of 0.793 (95% CI 0.748–0.832) for 90-day ACLF, versus 0.711 (0.661–0.756) for FS0-MELD (ΔAUC = 0.082; P < 0.001).

Three immune-metabolic dimensions derived from admission biomarkers improve ACLF and mortality prediction beyond conventional scores in AD of cirrhosis, with immunoparalysis showing the strongest prognostic association.

Early breast cancer may induce a systemic immune response before abundant tumor-derived material reaches the circulation, creating a potential source of amplified liquid-biopsy biomarkers. However, the extent to which host-response signatures can support early detection or population screening before diagnosis remains uncertain. This structured narrative review examines the biological basis, analytical platforms, evidence, clinical roles, and translational requirements of circulating autoantibodies, leukocyte transcriptomic and epigenetic profiles, immune-cell phenotypes, adaptive immune-receptor repertoires, soluble mediators, extracellular vesicles, and integrated multi-omics. PubMed/MEDLINE and citation networks were searched through August 31, 2026 using a predefined diagnostic review framework. Evidence was organized by intended use, sample timing, comparator spectrum, and validation maturity, with appraisal informed by established diagnostic-accuracy and prediction-model standards. Proof-of-concept estimates include a mean area under the curve of 0.96 for a machine-learning T-cell receptor model in 98 women, 80.8% sensitivity and 61.6% specificity for a 28-autoantibody panel, and an external-validation area under the curve of 0.951 for a 20-analyte proteome-metabolome model involving 662 participants. These estimates are not directly comparable: most derive from retrospective case-control or diagnostic cohorts with established cancer, healthy or benign comparators, post-diagnosis sampling, data-driven thresholds, and limited independent validation. Consequently, discrimination between known cases and controls must not be equated with detection of occult disease or population screening utility. Breast-specific prediagnostic evidence and screening validation remain sparse. Host-response signatures are therefore best considered investigational, complementary biological sensors rather than replacements for mammography. Their most plausible future roles include triage after equivocal imaging, enrichment for supplemental imaging, and longitudinal surveillance in high-risk populations. Translation requires prospective prediagnostic cohorts, representative benign and inflammatory controls, locked algorithms, high-specificity performance, calibration at screening prevalence, external validation, subgroup fairness, reproducibility, and evidence that testing improves cancer yield or stage distribution without unacceptable false-positive procedures, overdiagnosis, cost, or inequity.

The huge burden of type 1 diabetes mellitus (T1DM) has been a source of concern globally since the Industrial Revolution in the 18th–19th centuries. To this end, studies have shown that certain environmental changes that accompanied the Revolution may have increased the risk and burden of the disease in genetically predisposed individuals. However, documented studies that synthesize these environmental triggers are scarce. As a result, the current study was conceived to synthesize the environmental triggers of T1DM to boost public awareness. Relevant information was retrieved from reputable academic databases; namely, Scopus, PubMed, SpringerLink, and Embase. The results showed that chemical exposure, viral infection, gut microbiome disruption, vitamin and mineral deficiencies, inadequate or exclusive breastfeeding, as well as early exposure to infant feeding formulas could increase the risk and burden of T1DM in genetically predisposed individuals. As a consequence, these triggers could compromise the expression of certain genes involved in insulin synthesis and immune function, such as the human leukocyte antigen (HLA), insulin (INS), cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), and protein tyrosine phosphatase non-receptor type 22 (PTPN22) genes. This would result in a dysfunctional immune system in which immune cells, such as T-cells and B-cells and molecules, such as cytokines would attack self-tissues, thus causing autoimmunity of the pancreatic beta cells. Environmental triggers could also induce the T1DM pathophysiology by modifying the epigenome of the mentioned genes. Furthermore, some epigenetic changes could be reversed, which would infer that treatment procedures that would include the pathophysiology of the environmental triggers could be more effective.

Emerging evidence suggests that RNA-binding motif (RBM) proteins are involved in hepatocarcinogenesis and act either as oncogenes or tumor suppressors. The objective of this study was to investigate the role of RBM34, an RBM protein, in hepatocellular carcinoma (HCC).

We first examined the expression of RBM34 across cancers. The correlation of RBM34 with clinicopathological features and the prognostic value of RBM34 for HCC was then investigated. Functional enrichment analysis of RBM34-related differentially expressed genes (DEGs) was performed to explore its biological function. RNA sequencing (RNA-seq) was applied to identify downstream genes and pathways affected upon RBM34 knockout. The correlation of RBM34 with immune characteristics was also analyzed. The oncogenic function of RBM34 was examined in in vitro and in vivo experiments.

RBM34 was highly expressed in hepatocellular carcinoma and correlated with poor clinicopathological features and prognosis. RBM34 was positively associated with tumor immune cell infiltration, biomarkers of immune cells, and immune checkpoint expression. A positive correlation was also observed between RBM34, T cell exhaustion, and regulatory T cell marker genes. Knockout of RBM34 significantly inhibited cell proliferation, migration, and xenograft tumor growth, and sensitized HCC cells to sorafenib treatment. RBM34 inhibition reduced FGFR2 expression and affected PI3K-AKT pathway activation in HCC cells.

Our study suggests that RBM34 may serve as a new prognostic marker and therapeutic target of HCC.

Naringenin is an anti-inflammatory flavonoid that has been studied in chronic liver disease. The mechanism specific to its antifibrosis activity needs further investigation This study was to focused on the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) pathway in hepatic stellate cells and clarified the antifibrosis mechanism of naringenin.

The relationship between the cGAS-stimulator of interferon genes (STING) pathway and liver fibrosis was analyzed using the Gene Expression Omnibus database. Histopathology, immunohistochemistry, fluorescence staining, Western blotting and polymerase chain reaction were performed to assess gene and protein expression levels associated with the cGAS pathway in clinical liver tissue samples and mouse livers. Molecular docking was performed to evaluate the relationship between naringenin and cGAS, and western blotting was performed to study the expression of inflammatory factors downstream of cGAS in vitro.

Clinical database analyses showed that the cGAS-STING pathway is involved in the occurrence of chronic liver disease. Naringenin ameliorated liver injury and liver fibrosis, decreased collagen deposition and cGAS expression, and inhibited inflammation in carbon tetrachloride (CCl4)-treated mice. Molecular docking found that cGAS may be a direct target of naringenin. Consistent with the in vivo results, we verified the inhibitory effect of naringenin on activated hepatic stellate cells (HSCs). By using the cGAS-specific agonist double-stranded (ds)DNA, we showed that naringenin attenuated the activation of cGAS and its inflammatory factors affected by dsDNA. We verified that naringenin inhibited the cGAS-STING pathway, thereby reducing the secretion of inflammatory factors by HSCs to ameliorate liver fibrosis.

Interrupting the cGAS-STING pathway helped reverse the fibrosis process. Naringenin has potential as an antihepatic fibrosis drug.