Sun Yat-sen University Cancer Center

Joint learning on diverse ultrasonic source scenarios presents a challenge in preserving stable generalization due to the combination of heterogeneity of different sources and the inconsistency of joint learning features. Previous joint learning studies, which are not source-resilient frameworks, may not preserve stable generalization when trained on diverse source scenarios. Furthermore, the limited variations in single-source data and the interference from ultrasound imaging, which are common in ultrasonic source scenarios, further decrease generalization. To address these problems, we proposed a source-resilient joint learning framework consisting of three stages: 1) Source transforming, where our 1-to-N transformation unifies diverse source scenarios for source-resiliency. 2) Our feature enhancement modules model the source-resilient joint learning network, including a manifold-constraint normalization module (MCNM) for addressing heterogeneity by minimizing manifold-based loss, a task-consistent attention module (TCAM) shares the multi-scale features with self-attention to address inconsistency, and an adaptive feature-shifting module (AFSM) for feature-level augmentation to overcome single-source data. 3) Our ultrasound-hybrid linear mapping (USmapping) cascades speckle randomization and mask-guiding Monge-Kantorovitch linear mapping to achieve ultrasonic style randomization for addressing the interference of ultrasonic data. Our framework was evaluated on eight ultrasound datasets from various scanners at multiple centers and surpassed previous comparable studies in both segmentation (DSC$WAvg$ of 75.7%) and classification (AUROC$WAvg$ of 68.8%) tasks. Our framework has the potential to serve as a general framework for enhancing the performance of joint learning under diverse ultrasonic source scenarios.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally; however, the molecular drivers remain unclear. Dysregulated cholesterol metabolism is a hallmark of HCC and contributes to tumor progression. The Niemann-Pick type C1 protein (NPC1), a lysosomal cholesterol transporter, is overexpressed in cancers; however, its oncogenic mechanisms in HCC remain unclear. In this study, we identified NPC1 as a critical regulator of HCC progression through dual mechanisms involving p53 destabilization and modulation of cholesterol metabolism. Analysis of the clinical data revealed that NPC1 was significantly upregulated in HCC tissues and correlated with poor prognosis. Functional studies have demonstrated that NPC1 silencing suppresses HCC cell proliferation, both in vitro and in vivo. Mechanistically, NPC1 interacts with deubiquitinase ubiquitin-specific protease 7 (USP7), disrupting its binding to p53 and enhancing p53 ubiquitination and proteasomal degradation. Concurrently, NPC1 modulates cholesterol synthesis and distribution via the p53-SREBP2 axis, and p53 knockdown reverses the cholesterol reduction caused by NPC1 silencing. The pharmacological activation of p53 reversed the decrease in cholesterol levels mediated by the overexpression of NPC1. These findings reveal that NPC1 is a multifaceted oncoprotein in HCC, linking cholesterol metabolism to p53 regulation and highlighting its potential as a therapeutic target for HCC intervention.

BackgroundThis study aimed to evaluate the knowledge, attitudes, and practices (KAP) related to nasopharyngeal carcinoma (NPC) among young adults and students, a key subgroup of the general population, in Southern China.MethodsA cross-sectional survey was conducted between February 6 and March 5, 2025, targeting individuals from the general population in southern China. Structural equation modeling (SEM) analysis was employed to examine the direct and indirect relationships among KAP dimensions.ResultsA total of 664 valid questionnaires were obtained. Among the respondents, 421 (63.4%) were female, and 335 (50.5%) identified as students. The knowledge, attitude, and practice scores were 7.99 ± 3.80 (possible range: 0–15), 34.45 ± 4.85 (possible range: 8–40), and 43.88 ± 7.30 (possible range: 10–50), respectively. SEM analysis demonstrated that knowledge had a significant direct effect on attitude (β = 0.329, P < 0.001), while attitude had a strong direct effect on practice (β = 0.866, P < 0.001). Although the direct effect of knowledge on practice was not statistically significant (β = 0.013, P = 0.641), an indirect effect of knowledge on practice through attitude was observed (β = 0.285, P < 0.001).ConclusionYoung adults and students in Southern China exhibit low knowledge of NPC but demonstrates positive attitudes and practices. Future targeted health education interventions could enhance public knowledge, thereby further strengthening positive attitudes and promoting more effective preventive behaviors in clinical and community settings.

Patients with peripheral T cell lymphoma (PTCL) who achieved tumor response with first-line standard therapy were at high risk of disease relapse. We explored golidocitinib (150 mg once daily) as maintenance therapy for this group of patients (JACKPOT26, NCT06511869). This study included two cohorts: patients achieving a complete response (Cohort 1 (CR), N = 30) and a partial response (Cohort 2 (PR), N = 18) during induction stage. All enrolled patients were transplant ineligible or did not have a transplant plan. All dosed patients were included in the efficacy and safety analysis. In Cohort 1, the 24-month disease free survival (DFS) rate was 74.2% with golidocitinib treatment. In nodal subtypes (AITL, NOS, ALK- ALCL), the 24-month DFS rate was 62.7%. In Cohort 2, median progression free survival (PFS) was 17.4 months, and 24-month PFS rate was 48.6%. Nine out of 18 patients with initial PR achieved complete response, leading to a complete response rate of 50.0%, and median duration of response of 23.9 months. The most common ≥grade 3 treatment-related treatment-emergent adverse events (TRAEs) were hematological adverse events in nature, including neutrophil count decreased (47.9%), white blood cell count decreased (31.3%), lymphocyte count decreased (14.6%) and leukopenia (12.5%). The majority of these TRAEs were reversible and clinically manageable. TRAEs leading to treatment interruption and discontinuation occurred in 60.4% and 10% of patients, respectively. No TRAEs leading to fatal outcomes were reported. This study suggests the potential of golidocitinib as maintenance therapy for patients with PTCL.

MicroRNAs are promising liquid biopsy biomarkers, but their clinical translation is hindered by detection challenges, including low abundance, high sequence similarity, and background interference. Here we present SE-SPTM-PCR, a detection platform integrating selective miRNA enrichment using locked nucleic acid probes with specific probe terminal mediated RT-qPCR. We show that SE-SPTM-PCR eliminates nonspecific amplification and achieves 100-fold higher sensitivity than conventional stem-loop RT-qPCR. In clinical studies, SE-SPTM-PCR significantly improves hsa-miR-92a-3p performance for colorectal cancer detection, increasing its AUC from 0.72 to 0.85 in 48 patients versus 48 controls. Additionally, SE-SPTM-PCR also restores utility to two abandoned biomarkers: For HCMV reactivation monitoring in 32 DNA positive and 32 DNA negative hematopoietic stem cell transplant recipients, hcmv-miR-UL22A-5p achieves an AUC of 0.95. For nasopharyngeal carcinoma, ebv-miR-BART3-3p reaches a perfect AUC of 1.0 in 40 patients and 40 controls. This platform provides a robust tool for miRNA-based liquid biopsy, offering enhanced diagnostic accuracy to support early disease detection and personalized treatment strategies.