Hepatitis B virus (HBV) genotype C is common in East Asia and is associated with poor outcomes, particularly liver cirrhosis and hepatocellular carcinoma (HCC). Clinically, genotype C infection is generally associated with persistent viral replication, later HBeAg seroconversion, more active hepatic inflammation, and an increased risk of HCC. Current evidence suggests that these features are driven by several key molecular events, including the A1762T/G1764A double mutation in the basal core promoter, the G1896A mutation in the precore region, abnormal hepatitis B virus X protein function, and viral integration. Together, these changes may reshape viral transcription, antigen expression, host immune interactions, and oncogenic signaling, thereby contributing to disease progression and hepatocarcinogenesis. Other factors, such as epigenetic changes, dysregulated DNA damage responses, impaired tumor protein p53 function, and disrupted autophagy, may also be involved, although their exact roles remain unclear. Notably, even after effective viral suppression with potent nucleos(t)ide analogs, patients with genotype C may still have a relatively high residual risk of HCC. This review summarizes the molecular virological features, pathogenic mechanisms, immune dysregulation, and clinical significance of HBV genotype C, and discusses the potential value of genotype information in risk stratification, long-term surveillance, and clinical assessment of chronic hepatitis B.

Observational studies indicate frequent associations between systemic lupus erythematosus (SLE) and various hematologic disorders, yet causal inferences are limited by confounding and reverse causality. We therefore applied a bidirectional Mendelian randomization (MR) design to assess potential genetic causal associations of SLE with specific hematologic conditions.

We used European-ancestry GWAS summary statistics for SLE (5,201 cases, 9,066 controls) and five hematologic outcomes (vitamin B12 deficiency anemia (B12DA), myelodysplastic syndrome (MDS), immune thrombocytopenia (ITP), agranulocytosis (AGC), iron deficiency anemia (IDA)) from FinnGen. The primary analysis used inverse-variance weighting, supplemented by MR-Egger and weighted median methods, with comprehensive sensitivity analyses, including heterogeneity tests, pleiotropy assessment, and leave-one-out analysis.

Bidirectional MR analysis revealed that genetically predicted SLE increased the risk of B12DA (odds ratio (OR) = 1.08, P < 0.001), and genetically predicted B12DA was associated with an increased risk of SLE (OR = 2.22, P = 1.6 × 10−29). The MDS → SLE association was nominally significant (P = 0.023) but did not survive Bonferroni correction (P < 0.005) and was inconsistent across MR methods. No significant genetic associations were found between SLE and ITP, AGC, or IDA in either direction (all P > 0.005).

This bidirectional MR study provides genetic evidence that SLE increases the risk of B12DA, whereas the reverse direction (B12DA → SLE) should be interpreted cautiously because it was based on only five instruments and was not supported by the Steiger directionality test. No robust genetic associations were found for ITP, AGC, IDA, or MDS. Clinically, monitoring B12DA in SLE patients may be warranted, although screening recommendations await prospective validation.

Anti-anxiety medications may cause adverse effects and can be associated with long-term health risks. Rooibos tea (Aspalathus linearis) contains polyphenolic compounds that may confer health benefits. This study aims to investigate the effects of green rooibos extract supplementation on anxiety levels in adults with mild-to-moderate anxiety.

This double-blind, placebo-controlled, randomized controlled trial will enroll 60 adults aged 18-65 years with mild-to-moderate anxiety. Participants will receive either green rooibos extract (19.25 mg aspalathin per capsule; n = 30) or placebo (n = 30). They will take one capsule each morning during the first week and two capsules each morning during the subsequent 7 weeks. The anxiety subscale of the 21-item Depression, Anxiety and Stress Scale will be the primary outcome and will be assessed from baseline to post-intervention. Secondary outcomes will include salivary biomarkers, heart rate variability, sleep quality, and dietary intake. Measurements will be collected at baseline, mid-intervention, and post-intervention.

The findings may help determine whether green rooibos extract supplementation is associated with reduced anxiety and improvements in related health markers in adults with mild-to-moderate anxiety.

Randomized controlled trials (RCTs) have been conducted to evaluate treatment efficacy for metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis. This study aimed to compare the effectiveness and safety of 11 promising targets among adults with MASLD.

PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, Scopus, and Embase were searched from inception to November 20, 2024. The primary outcomes were fibrosis improvement ≥1 stage without worsening of steatohepatitis and steatohepatitis resolution without worsening of fibrosis. Additional outcomes included reductions in liver fat content, liver enzymes, metabolic profiles, and selected safety outcomes. The surface under the cumulative ranking curve (SUCRA) was used to rank efficacy.

Of 11,584 articles screened, 44 eligible RCTs (11,410 participants, 33 medications) were included. For fibrosis improvement, d-(R)-pioglitazone (SUCRA: 79.3) and fibroblast growth factor (FGF) 21 analogs (SUCRA: 71.9) ranked higher. For steatohepatitis resolution, glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) dual receptor agonists (RAs) (SUCRA: 91.7) ranked higher. Co-agonists of GLP-1/GIP/GCG and GLP-1/GCG receptors ranked higher for relative and absolute changes in liver fat content, respectively. For liver enzymes and glucose improvement, the combination of a GLP-1 RA and an acetyl-coenzyme A carboxylase inhibitor ranked higher. GLP-1 RAs, peroxisome proliferator-activated RAs, and FGF21 analogs showed favorable effects on lipid profile improvement.

Incretin-based co-agonists and FGF21 analogs showed favorable profiles across key endpoints, while d-(R)-pioglitazone and GLP-1/GIP dual RAs ranked higher for fibrosis improvement and steatohepatitis resolution, respectively. SUCRA rankings should be interpreted in conjunction with effect sizes, uncertainty, and available safety data.

Hepatic sinusoidal obstruction syndrome (HSOS) is a life-threatening liver vascular disorder with limited treatment options. HSOS results from the activation and injury of liver sinusoidal endothelial cells (LSECs). Berberine (BBR) has been shown to protect endothelial cells in various diseases. However, whether BBR can alleviate liver injury and LSEC disruption in HSOS remains unclear. In this study, we aimed to evaluate the effect of BBR on HSOS.

Two mouse models of HSOS were established using monocrotaline or oxaliplatin. Mice in the treatment groups received a low dose (100 mg/kg) or a high dose (200 mg/kg) of BBR daily. Histology, scanning electron microscopy, immunofluorescence, and flow cytometry were used to evaluate the therapeutic effects of BBR. Cell co-culture, Transwell assays, qRT-PCR, and Western blotting were performed to investigate the molecular pathways involved.

BBR treatment dose-dependently reduced liver injury and disruption of LSECs in murine HSOS models. Moreover, BBR significantly reduced hepatic neutrophil infiltration, thereby attenuating neutrophil-mediated injury to LSECs. Additionally, BBR inhibited the effect of injured LSECs on neutrophil activation. Mechanistically, injured LSECs were identified as one of the major sources of CXCL1 in HSOS, and BBR downregulated CXCL1 expression in injured LSECs by inhibiting MAPK signaling.

In this study, we demonstrate that BBR ameliorates HSOS by inhibiting endothelial-mediated neutrophil recruitment and activation. BBR may be a promising therapeutic option for HSOS treatment.