Fourth Hospital of Hebei Medical University

ObjectivesATP-binding cassette sub-family B member 1 (ABCB1) is closely associated with multidrug resistance (MDR) in colorectal cancer; however, safe and effective clinical treatment options remain limited. This study aimed to evaluate electroacupuncture, a traditional Chinese medicine technique, for its potential to overcome ABCB1-mediated MDR in colorectal cancer and investigate the underlying mechanisms.MethodsThe tumor-inhibitory effects of electroacupuncture were investigated in nude mice with ABCB1 overexpression-induced MDR. Chemotherapy drug metabolism in tumor tissues and blood was assessed using pharmacokinetic analysis. In vivo fluorescence imaging was employed to monitor the accumulation of the ABCB1 substrate Rhodamine 123 within tumors. ABCB1 expression was analyzed using Western blotting, polymerase chain reaction (PCR), and immunofluorescence. Proteomic and bioinformatic analyses were conducted to explore the mechanisms through which electroacupuncture overcomes ABCB1-mediated drug resistance.ResultsElectroacupuncture significantly enhanced the sensitivity of ABCB1-mediated MDR nude mice to paclitaxel, markedly inhibiting tumor growth and promoting apoptosis. Tumor drug concentrations increased, while the expression of hypoxia-inducible factor 1-alpha (HIF1A) and its downstream target, ABCB1, decreased. Proteomic analyses suggested that extracellular matrix (ECM) remodeling plays a key role, indicated by decreased TIMP-1 and increased collagen expressions (collagen alpha-1(I) chain [COL1A1], collagen alpha-2(I) chain [COL1A2], and collagen alpha-1 (XVIII) chain [COL18A1]). Collectively, these findings indicate that electroacupuncture may influence tumor mechanical properties and the hypoxic microenvironment by modulating the balance between ECM degradation and deposition, providing a potential mechanistic explanation for the reversal of ABCB1-mediated MDR.ConclusionElectroacupuncture may reverse ABCB1-mediated tumor MDR, potentially through ECM remodeling and improvement of the tumor mechanical microenvironment. These insights provide a basis for developing new strategies to combat clinical drug resistance.

ObjectiveThe synergistic carcinogenic effect of areca nut chewing and tobacco exposure is a major risk factor for oral squamous cell carcinoma (OSCC). However, the molecular mechanisms, particularly related to N6-methyladenosine (m6A) modification, remain unclear. This study explores the potential mechanisms by which arecoline and 4-nitroquinoline-1-oxide (4-NQO) induce OSCC, focusing on m6A regulatory factors and key targets.MethodsTranscriptional data were obtained from Gene Expression Omnibus (GEO), with differentially expressed genes (DEGs) identified using the limma package. The intersection of DEGs and 21 m6A regulators was analyzed, and their prognostic relevance was validated with The Cancer Genome Atlas (TCGA) data. Arecoline and 4-NQO targets were identified through online databases, and compound-target and protein-protein interaction (PPI) networks were constructed. Core targets were selected using Degree, MCC, and FRIENDS algorithms. Spearman analysis assessed correlations with m6A factors, and molecular docking was performed to verify binding properties.ResultsHeterogeneous Nuclear Ribonucleoprotein C (HNRNPC), AlkB Homolog 5 (ALKBH5), and ELAV Like RNA Binding Protein 1 (ELAVL1) were identified as key genes. High HNRNPC expression correlated with poor prognosis. AKT Serine/Threonine Kinase 1 (AKT1) was the core target across algorithms, with significant correlations between AKT1 and m6A factors. Molecular docking indicated potential binding between AKT1 and the compounds.ConclusionThis study establishes a regulatory network linking arecoline/4-NQO, AKT1, m6A factors, and OSCC, and identifies key molecular targets and mechanisms underlying the carcinogenic process. These findings provide a theoretical foundation for understanding the pathogenesis of OSCC and developing targeted strategies for early intervention and treatment.

Background/Objectives: Bone is the most common organ affected by distant metastasis in advanced breast cancer, and the development of skeletal-related events (SREs) often leads to significant deterioration in patients' quality of life and survival outcomes. In this study, we aimed to explore the risk factors associated with bone metastasis in breast cancer and to develop a predictive nomogram for identifying high-risk patients, which may facilitate timely preventive interventions and improve clinical prognosis. Methods: A retrospective analysis was conducted on 672 patients with breast cancer who underwent surgery at the Fourth Hospital of Hebei Medical University (Shijiazhuang, China) between 2013 and 2023; this cohort served as the training set. Clinical and pathological characteristics potentially influencing bone metastasis-including age, menopausal status, histological grade, affected side, maximum tumor diameter, lymph node staging, TNM staging, ER status, PR status, HER-2 status, Ki-67, molecular subtypes, vascular tumor thrombus, nerve infiltration and visceral metastasis-were collected. The median follow-up time was 42 months. Patients were stratified into two cohorts based on whether postoperative bone metastasis occurred, with groups matched according to Tumor-Node-Metastasis (TNM) stage. Univariate and multivariate logistic regression models were applied to identify independent factors associated with breast cancer bone metastasis, and a nomogram prediction model was constructed using the variables retained in the final analysis. For external validation, data from 2814 patients with breast cancer who underwent surgery between 2013 and 2021 were extracted from the U.S. Surveillance, Epidemiology, and End Results database. Results: The multivariate logistic regression analysis revealed that histological grade (p = 0.002), progesterone receptor (PR) negativity (p = 0.001), human epidermal growth factor receptor 2 (HER-2) negativity (p = 0.002) and visceral metastasis (p < 0.001) were identified as independent predictors of bone metastasis in breast cancer. A nomogram predictive model was established using these four factors. The area under the receiver operating characteristic curve was 0.720 (95% confidence interval (CI): 0.6797-0.7607) for the training cohort and 0.701 (95% CI: 0.6813-0.7205) for the external validation cohort. Decision curve analysis further confirmed the clinical applicability of the model. Conclusions: The present study confirms that histological grade, PR status, HER-2 status and visceral metastasis are independent factors associated with bone metastasis in breast cancer. The constructed nomogram may effectively predict breast cancer-related bone metastasis and could serve as a practical tool for clinical decision-making.

Abstract Precise evaluation of cervical lymph node metastasis (CLNM) and genetic mutations (BRAF V600E /TERT promoter, TERTp) is pivotal for tailoring surgical and prognostic evaluation and adjuvant strategies in thyroid cancer (TC). Although current methods have limitations, we aim to develop deep learning (DL) models to predict CLNM and genetic mutations from TC frozen sections. We developed a DL framework using 2499 frozen‐section whole‐slide images from 2176 TC patients across five centers. The model was trained with a transfer learning‐based feature extractor and an attention‐based multiple instance learning (MIL) classifier, and validated on both internal and external cohorts. StyleGAN3‐based data augmentation was employed to tackle class imbalance for TERTp prediction, while interpretability was assessed via attention heatmaps and Leiden clustering. The CLNM prediction model achieved a patient‐level AUROC of 0.918 internally and 0.803–0.885 across three external validation datasets. For BRAF V600E prediction, AUROCs attained 0.814 internally and spanned 0.750––0.811 in external validation. In TERTp mutation prediction, GAN‐based augmentation increased the AUROC to 0.804 (internal) and 0.732 (external), up from 0.782 and 0.724, respectively. Attention maps visualized CLNM correlations with invasive tumor margins, while mutations localized to specific cellular morphology features. Our DL models accurately predict CLNM and genetic mutations from TC frozen sections, potentially reducing unnecessary procedures and providing a rapid alternative to traditional molecular testing.

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.

ObjectiveNeutrophil-to-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR), Red-cell-distribution width (RDW) and Platelet-distribution width(PDW) have been proved to be related to the severity of a variety of diseases and poor prognosis. But their predictive value in neonatal pneumonia is still unknown. Therefore, this study explored the predictive value of NLR, PLR, RDW and PDW in the adverse prognosis of neonatal pneumonia.MethodsWe retrospectively analyzed 132 neonates with pneumonia treated in our hospital from April 2022 to October 2024. At the same time, 50 healthy newborns delivered in our hospital during the same period were selected as the control group. The levels of NLR, PLR, RDW and PDW in children with different disease severity and prognosis were analyzed; The correlation between NLR, PLR, RDW, PDW levels and disease severity was analyzed, and the predictive value for the adverse prognosis of neonatal pneumonia.ResultsAmong 132 children, 65 were mild, 44 moderate and 23 severe; 26 cases had poor prognosis. The levels of NLR, PLR, RDW and PDW in children with different disease severity were significantly different (P<0.05). Spearman test showed that NLR, PLR, RDW, PDW were significantly positively correlated with the severity of neonatal pneumonia (P<0.05). Multivariate logistic regression analysis showed that NLR, PLR, RDW and PDW were the related factors influencing the poor prognosis of neonatal pneumonia (p<0.05). ROC curve analysis showed that the value of combined prediction of four indicators for poor prognosis of neonatal pneumonia was higher than that of single indicators, and the sensitivity of combined prediction was 100%, and the specificity was 94.9%.ConclusionNLR, PLR, RDW, PDW were positively correlated with the severity of neonatal pneumonia, and the value of combined prediction of poor prognosis was higher.

A teenage girl presented with sudden lower abdominal pain following exercise, prompting initial consideration of ovarian cyst rupture by the attending emergency physician. However, the presence of unilateral renal absence on Computed Tomography (CT) imaging strongly suggested a reproductive tract malformation, later confirmed by Magnetic Resonance Imaging (MRI). Surgical exploration during laparotomy revealed a functional non-communicating rudimentary horn with associated ovarian endometriosis, in the setting of chronic dysmenorrhea. This rare case underscores the essentiality of comprehensive preoperative assessment to identify anatomical variations, guide surgical decision-making, and prevent diagnostic errors. Subsequent literature review focused on the co-occurrence of endometriosis in rudimentary horns and congenital urinary system abnormalities.