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.

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.

Brain tumors represent a common class of life-threatening neoplastic conditions. The core objective of neurosurgery is to achieve maximal safe resection of tumors while preserving the patient’s neurological function. Intraoperative ultrasound (IOUS) assists surgeons in achieving complete lesion removal, helping to avoid insufficient resection or excessive excision of normal tissue, thereby reducing surgical morbidity. Contrast-enhanced ultrasound (CEUS), through harmonic imaging, enables more precise localization of lesions and intracranial structures. This review focuses on the synergistic value of IOUS and CEUS in brain tumor surgery. It traces the technological evolution from two-dimensional ultrasound to elastography, color Doppler flow imaging, microvascular flow imaging, artificial intelligence, and beyond, with an emphasis on CEUS for cranial tumors. It also examines the clinical applications of IOUS and CEUS in precise resection, residual tumor identification, vascular protection, boundary differentiation from peritumoral edema, and prognostic assessment. The review concludes by summarizing diagnostic performance, current limitations, and future directions, offering neurosurgeons a theoretical and practical framework for optimizing intraoperative guidance.

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.

Emerging diseases are those that appear in a population for the first time or previously existed, but rapidly increase in incidence or geographic range. During the coronavirus disease 2019 (COVID-19) pandemic, ethnopharmacological practices became prominent in Nigeria because herbal remedies were affordable, locally accessible, and supported by longstanding cultural trust. However, despite broad public use and some regulatory progress, evidence for the safety, efficacy, standardization, and clinical application of these remedies remains limited. This narrative review examines the integration of ethnopharmacology into Nigeria’s COVID-19 response, evaluates its strengths, constraints, and lessons, and considers future pathways for incorporating ethnopharmacological practices into epidemic preparedness and response strategies. It reviews literature and regulatory information published from 2015 to 2025, focusing on herbal remedies used during the pandemic, regulatory listing processes, and key research gaps. Common remedies were derived from Zingiber officinale, Allium sativum, Citrus limon, Curcuma longa, and Garcinia kola. The National Agency for Food and Drug Administration and Control in Nigeria accelerated toxicological testing and listed 14 local herbal medicines, including Pax Herbal Cugzin, Niprimune, and IHP Detox Tea. This established a baseline safety for human consumption but did not validate therapeutic efficacy against severe acute respiratory syndrome coronavirus 2, which requires rigorous clinical trials. Although some formulations showed promising findings in preliminary clinical, in silico, and in vitro studies, the evidence was constrained by small pilot samples, absence of multiphase randomized controlled trials, insufficient in vivo pharmacokinetic data, and difficulties in isolating active compounds necessary for batch-to-batch consistency. Strengthening Nigeria’s resilience to future epidemics will require sustained investment in scientific research infrastructure, toxicogenomic and metabolomic studies, robust intellectual property frameworks for indigenous knowledge, and transparent public communication to reduce misinformation and product misuse.

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.

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.