In contemporary practice, elevated 24-hour urinary copper excretion (24-h UCE) often triggers referral for suspected Wilson disease (WD). In this hypercupriuric referral setting, interpretation of 24-h UCE may be distorted by spectrum effects. In this study, we aimed to compare conventional copper biomarkers in hypercupriuric referrals and evaluate whether a Leipzig-aligned ceruloplasmin (Cp) framework could provide a clinically useful triage approach.

We retrospectively studied consecutive, untreated patients evaluated for suspected WD with hypercupriuria between February 2017 and February 2025. The final diagnosis was established using a prespecified Leipzig-based algorithm, with ATP7B testing when indicated. Diagnostic performance of Cp and 24-h UCE was compared. A prespecified Cp three-zone framework was evaluated using <0.10 g/L, 0.10–0.20 g/L, and >0.20 g/L as high-probability, indeterminate, and low-probability zones, respectively.

Among 541 untreated hypercupriuric patients, 65 had WD and 476 had adjudicated non-WD liver disease. Cp outperformed 24-h UCE for diagnosing WD (AUROC, 0.988 vs. 0.762). The optimal Cp cutoff was 0.15 g/L, with 90.8% sensitivity and 97.7% specificity. Cp < 0.10 g/L defined a high-probability zone with 98.0% WD prevalence, whereas Cp > 0.20 g/L defined a low-probability zone with 0.5% WD prevalence. Among non-WD controls, higher urinary copper was independently associated with higher bilirubin, prolonged international normalized ratio, and lower albumin.

In hypercupriuric referrals for suspected WD, Cp retained strong diagnostic performance and outperformed 24-h UCE. A Leipzig-aligned Cp three-zone framework may support probability-based triage in contemporary referral practice.

Despite the surging global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) and related liver fibrosis, effective treatments remain limited. While the traditional Chinese medicine Juanyu-Xiaozhi Formula (JYXZF) is used against MASLD, its bioactive components and mechanisms are poorly understood. This study aimed to investigate the therapeutic effects of JYXZF and elucidate its underlying mechanisms of action.

The constituents of JYXZF were characterized using ultra-high-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS). Its efficacy was evaluated in a rat model of metabolic dysfunction-associated steatohepatitis (MASH) induced by a high-fat/calorie diet with high-fructose/high-glucose water, utilizing serum biochemistry, histology, and glucose/insulin tolerance tests. Mechanistic validation was performed in free fatty acid-treated human hepatocellular carcinoma cell line HepG2 (HepG2) cells and HepG2/human hepatic stellate cell line LX-2 (LX-2) co-culture models using luciferase assays, chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR), and activator protein 1 (AP-1) overexpression rescue experiments. The functional relevance of stearoyl-CoA desaturase 1 (SCD1) was further assessed in vivo through liver-targeted adeno-associated virus (AAV)-mediated Scd1 overexpression.

Flavonoids were identified as the main bioactive constituents. JYXZF administration alleviated metabolic dysfunction, reduced hepatic lipid accumulation, and attenuated inflammation and fibrosis in MASH rats. Multi-omics integration and machine learning-assisted target prioritization identified lipid metabolic and inflammatory pathways. Among these pathways, we selected the AP-1/peroxisome proliferator-activated receptor gamma (PPARγ)/SCD1-related lipogenic pathway for functional validation. Target perturbation experiments supported the functional involvement of AP-1 in the regulation of the PPARγ/SCD1 pathway and its contribution to the anti-steatotic effects of JYXZF.

JYXZF alleviates MASLD-associated steatosis and fibrosis via the AP-1/PPARγ/SCD1-related lipogenic axis, demonstrating its therapeutic potential for MASLD/MASH and providing a mechanistic basis for future clinical applications.

Apatinib has been shown to be efficacious in the treatment of gallbladder cancer. However, the underlying mechanisms remain unclear. This study aimed to explore pathways related to the antitumor effects of apatinib at the cellular level in gallbladder cancer.

NOZ and GBC-SD gallbladder cancer cells were treated with apatinib at concentrations of 0 μM, 10 μM, or 20 μM. The effect of apatinib on the proliferation of these cells was assessed using MTT and colony formation assays, and the effects of apatinib on cell cycle progression and DNA synthesis were evaluated using flow cytometry. Clinical cancer tissue samples, along with paired adjacent normal tissue samples, were obtained from 10 patients with gallbladder cancer. Immunohistochemistry, western blotting, and quantitative real-time polymerase chain reaction analyses were conducted to elucidate molecular changes induced by apatinib treatment.

Treatment with 20 μM apatinib significantly inhibited the expression of phosphorylated (p)-vascular endothelial growth factor receptor 2 (VEGFR2), p-AKT, and histone deacetylase 1 (HDAC1). Additionally, apatinib treatment led to upregulated expression of p-cyclin-dependent kinase 1, p21, and Bax, and downregulated expression of cell division cycle 25B, B-cell lymphoma 2, Snail, and Slug. Apatinib decelerated DNA replication and induced cell cycle arrest at the G2/M phase, consequently suppressing the proliferation of gallbladder cancer cells.

Apatinib inhibits the proliferation of gallbladder cancer cells, and the mechanism involves VEGFR2/AKT, HDAC1, and downstream genes. These findings provide a basis for further investigation into the molecular mechanisms underlying the inhibitory effect of apatinib in gallbladder cancer.

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.

Post-stroke dysphagia management research has primarily focused on screening, assessment, and intervention strategies, with limited objective indicators for evaluating nursing care quality. This study aimed to develop a dysphagia nursing quality evaluation index system for neurosurgical inpatients with stroke.

Using the “structure-process-outcome” three-dimensional quality model as the theoretical framework, a preliminary quality evaluation index system was constructed through literature analysis and group discussion. A two-round Delphi expert consultation was conducted among 25 purposively selected clinical experts from tertiary Class A hospitals, with inclusion criteria requiring a bachelor’s degree or higher, an intermediate professional title or above, and at least 10 years of clinical experience in stroke nursing or related fields. The analytic hierarchy process was used to determine indicator weights. Outcome measures included expert authority coefficients (Cr), Kendall’s W concordance coefficient, internal consistency reliability (Cronbach’s α), and the final indicator structure.

The Cr values were 0.87 and 0.88 across the two rounds. Kendall’s W concordance coefficient increased from 0.207 to 0.235 (P < 0.001), indicating statistically significant expert agreement. The final index system comprised 3 first-level indicators, 11 second-level indicators, and 44 third-level indicators, with all indicator definitions and weights determined. The overall Cronbach’s α was 0.86, indicating preliminary internal consistency.

This study developed a dysphagia nursing quality evaluation index system for neurosurgical inpatients with stroke using the three-dimensional quality model and the Delphi method. The system showed acceptable expert authority, statistically significant expert agreement, and preliminary internal consistency, suggesting potential applicability for nursing quality monitoring in neurosurgical wards and Neurosurgery Intensive Care Units. Further clinical validation is needed before routine implementation.

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.