Objective To explore the relationship between circadian rhythm genes and the occurrence, development, prognosis, and tumor microenvironment (TME) of lung adenocarcinoma (LUAD). Methods The Cancer Genome Atlas data were used to evaluate the expression, copy number variation, and somatic mutation frequency of circadian gene sets in LUAD. Gene ontology, Kyoto encyclopedia of genes and genomes, and gene set enrichment analysis were used to explore the potential mechanisms by which circadian rhythm genes affected LUAD progression. Cox regression, least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and random forest screened circadian genes and established prognostic models, and on this basis constructed nomogram to predict patients’ 1-, 3-, and 5-year survival rates. Kaplan-Meier survival curves, receiver operating characteristic (ROC) curves, and time-dependent ROC curves were drawn to evaluate the predictive ability of the model, and the external dataset of GEO further verified the prognostic value of the prediction model. In addition, we evaluated the association of the prognostic model with immune cells and immune checkpoint genes. Single cell RNA sequencing (scRNA-seq) analysis was used to explore the molecular characteristics between prognostically relevant circadian genes and different immune cell populations in TME. Results Differentially expressed circadian rhythm genes were mainly enriched in biological processes related to cGMP-PKG signaling pathway, lipid and atherosclerosis, and JAK-STAT signaling pathway. Seven circadian rhythm genes: LGR4, CDK1, KLF10, ARNTL2, RORA, NPAS2, PTGDS were screened out, and a RiskScore model was established. According to the median RiskScore, samples were divided into a high-risk group and a low-risk group. Compared with patients in the low-risk group, patients in the high-risk group showed a poorer prognosis (P<0.001). Immunological characterization analysis showed that there were differences in the infiltration of multiple immune cells between the low-risk group and high-risk group. Most immune checkpoint genes had higher expression levels in the high-risk group than those in the low-risk group, and RiskScore was positively correlated with the expression of CD276, TNFSF4, PDCD1LG2, CD274, and TNFRSF9, and negatively correlated with the expression of CD40LG and TNFSF15. The scRNA-seq analysis showed that RORA and KLF10 were mainly expressed in natural killer cells. Conclusion The prognostic model based on seven feature circadian rhythm genes has certain predictive value for predicting survival of LUAD patients. Dysregulated expression of circadian genes may regulate the occurrence, progression as well as prognosis of LUAD through affecting TME, which provides a possible direction for finding potential strategies for treating LUAD from the perspective of mechanism by which circadian disorder affects immune cells.

Background/Aims: Acetyl coenzyme A (acetyl-CoA) is one of the most essential metabolites in cell metabolism but its function and concentration in hepatocellular carcinoma (HCC) remain elusive and controversial. Methods: A comprehensive analysis of acetyl-CoA levels and acetyl-CoA synthetase 2 (ACSS2) expression across a range of samples, including patient specimens from both hepatitis B virus (HBV) positive and HBV negative HCC individuals, HBV-transgenic mouse HCC models, and multiple cell lines. Furthermore, to evaluate the functional significance of ACSS2 in HBV-related HCC, we implemented both genetic and pharmacological inhibition strategies targeting ACSS2. Molecular mechanism and mitophagy assessment were revealed by cleavage under target and tagmentation sequencing, RNA sequencing, bioinformatic analyses, transmission electron microscopy and JC-1 staining. Results: Our study revealed a distinct metabolic signature of HBV-related HCC, marked by elevated acetyl-CoA, which was driven by ACSS2. ACSS2 was upregulated by the carbohydrate response element-binding protein in HBV-related HCC. Furthermore, ACSS2 improved tumor cell proliferation, an effect that was dependent on its enzymatic activity. Mechanistically, ACSS2-induced acetyl-CoA accumulation activated voltage-dependent anion channels 1 transcription through increased H3K27ac occupancy, which subsequently promoted mitophagy and HBV-related HCC tumorigenesis. Notably, targeting ACSS2 by depletion or inhibition with a catalytic inhibitor significantly suppressed tumor growth. Conclusions These findings not only illustrate the interplay between metabolic reprogramming, epigenetic modification, and tumorigenesis in the context of HBV infection, but also highlight ACSS2 as a novel metabolic vulnerability in HBV-related HCC. Therefore, targeting ACSS2 could be a novel strategy against HBV-related HCC.

Objective: To deeply explore the systemic management dilemmas affecting patients with chronic periodontitis in underdeveloped regions, providing practical pathways for achieving oral health equity. Methods: This study has been reviewed and approved by the Medical Ethics Committee, and written informed consent was obtained from the participants. Based on a comprehensive design integrating literature review and theory, an interview guide was developed. Using purposive sampling, semi-structured interviews were conducted with 20 patients diagnosed with chronic periodontitis who were from underdeveloped regions and attended the Stomatological Hospital of Southern Medical University between November 2025 and February 2026. The sample size was determined by data saturation. Data analysis employed Colaizzi’s seven-step method. Results: Through interview with 20 participants, three core themes were extracted, encompassing eight sub-themes: individual cognitive-behavioral dilemmas (cognitive limitations and passive coping, inefficient and superficial self-management, and economic and psychological barriers to seeking care); systemic and environmental structural obstacles (distrust in primary healthcare capabilities, and the limited buffering effect and constraints of medical insurance); and the need for health empowerment and support systems (authoritative knowledge and management skill guidance, aspirations for access to high-quality specialized medical resources, and sustained and reminder-based remote support). Conclusion Patients with chronic periodontitis in underdeveloped regions face a multidimensional dilemma composed of limited health literacy, poor adherence to health behaviors, weak primary care service capacity, uneven medical insurance coverage, and insufficient high-quality specialized medical resources. Patients’ health literacy should be advanced through innovative health education, primary care capacity should be strengthened for periodontal disease prevention and treatment, and it is recommended to prioritize the inclusion of initial periodontal therapy in outpatient coordination or chronic disease management, and a remote medical support system based on digital technology should be established.

Objective: To conduct a scoping review on the types, construction methods and predictive performance of health literacy prediction models based on machine learning methods, so as to provide the reference for the improvement and application of such models. Methods: Publications on health literacy prediction models conducted using machine learning methods were retrieved from CNKI, Wanfang Data, VIP, PubMed and Web of Science from inception to May 1, 2024. The quality of literature was assessed using the Prediction Model Risk of Bias ASsessment Tool. Basic characteristics, modeling methods, data sources, missing value handling, predictors and predictive performance were reviewed. Results: A total of 524 publications were retrieved, and 22 publications between 2007 and 2024 were finally enrolled. Totally 48 health literacy prediction models were involved, and 25 had a high risk of bias (52.08%), with major issues focusing on missing value handling, predictor selection and model evaluation methods. Modeling methods included regression models, tree-based machine learning methods, support vector machines and neural network models. Predictors primarily encompassed factors at four aspects: individual, interpersonal, organizational and society/policy aspects, with age, educational level, economic status, health status and internet use appearing frequently. Internal validation was conducted in 14 publications, and external validation was conducted in 4 publications. Forty-two models reported the areas under the receiver operating characteristic curve, which ranged from 0.52 to 0.983, indicating good discrimination. Conclusion Health literacy prediction models based on machine learning methods perform well, but have deficiencies in risk of bias, data processing and validation.

BACKGROUND:Neuregulin 1 has been shown to be characterized in cell proliferation,differentiation,and vascular growth.Human amniotic mesenchymal stem cells are important seed cells in the field of tissue engineering,and have been shown to be involved in tissue repair and regeneration. OBJECTIVE:To construct human amniotic mesenchymal stem cells overexpressing neuregulin 1 and investigate their proliferation and migration abilities,as well as their effects on wound healing. METHODS:(1)Human amniotic mesenchymal stem cells were in vitro isolated and cultured and identified.(2)A lentivirus overexpressing neuregulin 1 was constructed.Human amniotic mesenchymal stem cells were divided into empty group,neuregulin 1 group,and control group,and transfected with empty lentivirus and lentivirus overexpressing neuregulin 1,or not transfected,respectively.(3)Edu assay was used to detect the proliferation ability of the cells of each group,and Transwell assay was used to detect the migration ability of the cells.(4)The C57 BL/6 mouse trauma models were constructed and randomly divided into control group,empty group,neuregulin 1 group,with 8 mice in each group.Human amniotic mesenchymal stem cells transfected with empty lentivirus or lentivirus overexpressing neuregulin-1 were uniformly injected with 1 mL at multiple local wound sites.The control group was injected with an equal amount of saline.(5)The healing of the trauma was observed at 1,7,and 14 days after model establishment.Histological changes of the healing of the trauma were observed by hematoxylin-eosin staining.The expression of CD31 on the trauma was observed by immunohistochemistry. RESULTS AND CONCLUSION:(1)Human amniotic mesenchymal stem cells overexpressing neuregulin-1 were successfully constructed.The mRNA and protein expression of intracellular neuregulin 1 was significantly up-regulated compared with the empty group(P<0.05).(2)The overexpression of neuregulin 1 promoted the migratory ability(P<0.01)and proliferative ability of human amniotic mesenchymal stem cells(P<0.05).(3)Human amniotic mesenchymal stem cells overexpressing neuregulin 1 promoted wound healing in mice(P<0.05)and wound angiogenesis(P<0.05).The results showed that overexpression of neuregulin 1 resulted in an increase in the proliferative and migratory capacities of human amniotic mesenchymal stem cells,significantly promoting wound healing and angiogenesis.

Objective To investigate the value of ¹⁸F-FDG PET/CT metabolic parameters in the prognostic assessment of nasopharyngeal cancer patients. Methods The clinical data and PET/CT metabolic parameters of 185 nasopharyngeal cancer patients were retrospectively analyzed. The collected parameters were SUV_max, MTV, TLG, total metabolic tumor volume (TMTV) and whole-body total lesion glycolysis (WTLG). The ROC curve was used to determine the optimal cut-off values of PET/CT metabolic parameters. Univariate and multivariate Cox regression models were used to screen the independent prognostic factors. Kaplan–Meier curves were used to analyze the survival differences. Results The results of univariate Cox regression analysis showed that age, pathologic type, WTLG, TMTV, MTV, and TLG were closely associated with OS and PFS; and SUV_max was associated with PFS (P<0.05). Multivariate Cox regression analysis results showed that age, TMTV, and WTLG were the independent prognostic factors for OS and PFS (P<0.05). The combination of WTLG with T/N staging (AUC=0.781 and 0.781) and TMTV with T/N staging (AUC=0.800 and 0.790) yielded greater predictive accuracy than that of WTLG and TMTV alone (AUC=0.724 and 0.719) or T/N staging (AUC=0.593 and 0.575). Conclusion TMTV and WTLG are important prognostic predictors of nasopharyngeal carcinoma. TLG and MTV of primary lesions are prognostic factors for patients’ PFS and OS. SUV_max has limited prognostic value. Systemic metabolic indexes (TMTV and WTLG), when combined with T/N staging, can optimize prognostic stratification.

Objective To explore the relative positioning of the superior orbital fissure and internal carotid artery through CT three-dimensional reconstruction,and to provide anatomical references for safe dissection during surgeries involving the orbital apex from a radiological perspective.Methods Totally 64 cases(128 sides)of head and neck CT angiography were analyzed and Mimics 21.0 software was employed for three-dimensional reconstruction.Measurements were taken on the three-dimensional models,including the distance from the inner boundary of the superior orbital fissure to the anterior convexity,proximaldural ring,and distaldural ring of the internal carotid artery.Distances were also measured from the lower boundary of the superior orbital fissure to the anterior convexity,proximaldural ring,and distaldural ring of the internal carotid artery.Additionally,measurements were taken from the upper boundary of the superior orbital fissure to the anterior convexity,proximaldural ring,and distaldural ring of the internal carotid artery.Patient demographic data such as gender,age,and sphenoid sinus aeration were recorded,and anatomical variations were analyzed in correlation with the measured result.Results Distances were measured as follows,d1(6.32±1.98)mm,d2(7.13±2.66)mm,and d3(9.88±2.29)mm from the inner boundary of the superior orbital fissure to the anterior convexity,proximaldural ring,and distaldural ring of the internal carotid artery,respectively.Distances were also measured as d4(11.93±2.17)mm,d5(10.39±2.36)mm,and d6(16.18±2.28)mm from the lower boundary of the superior orbital fissure to the anterior convexity,proximaldural ring,and distaldural ring of the internal carotid artery,respectively.Distances from the upper boundary of the superior orbital fissure to the anterior convexity,proximaldural ring,and distaldural ring of the internal carotid artery were measured as d7(7.91±2.55)mm,d8(9.63±2.99)mm,and d9(10.09±2.72)mm,respectively.The relative distance between the superior orbital fissure and the cavernous segment of the internal carotid artery was significantly greater in males than in females.In patients under 20 years of age,d7-d9 were significantly smaller than in patients over 20 years old,with statistically significant differences.There was a correlation between the type of sphenoid sinus aeration and the main measured parameters d1-d6,while the degree of sphenoid sinus aeration and the presence of the superior orbital fissure were not significantly correlated with the main measured parameters.Conclusion Three-dimensional reconstruction based on CT angiography provides a better assessment of the distance between the superior orbital fissure and internal carotid artery.This method holds clinical reference value for orbital apex surgeries and ensures a safe dissection distance.

Objective To investigate the clinical efficacy and safety of endoscopic ultrasonography-guided(EUS-guided)enterocolon anastomosis in treating patients with malignant bowel obstruction(MBO).Methods The clinical data of 12 patients with MBO,who underwent EUS-guided enterocolon anastomosis at the Nanjing Drum Tower Hospital of China from April 2023 to December 2023,were collected.The perioperative clinical efficacy and safety were retrospectively analyzed.Results Successful EUS-guided enterocolon anastomosis was accomplished in all the 12 patients,with a technical success rate of 100％(12/12).The clinical success rate was 83.3％(11/12),one patient developed obstruction of the stent.The clinical symptoms were relieved in 2-68 hours after treatment,and the time to resume defecation and exhaust was(18.02±15.75)hours.Within one week after the operation,4 patients took liquid diet and 8 patients took semi-fluid diet.Each dimension score of the Quality of Life Core-30 scale of The European Organization for Research and Treatment of Cancer(EORTC QLQ-C30)was remarkably improved,the patient's overall health score was increased from preoperative median 5 points to postoperative 8 points(P＜0.001).During the operation,stent displacement occurred in 2 patients,and the operation was successfully completed after promptly taking remedial measures.After operation,11 patients developed fever(37.5-39.4 ℃),and all the patients were discharged smoothly after symptomatic treatment.No complication such as bleeding,perforation,or stent displacement occurred.Conclusion EUS-guided enterocolon anastomosis is clinically safe and effective,it can effectively relieve the clinical symptoms and improve the quality of life of patients with MBO.

Objective:To investigate the correlation between serum neuron-specific enolase (NSE) levels and poor neurological outcomes in cardiac arrest (CA) patients supported by veno-arterial extracorporeal membrane oxygenation (VA-ECMO).Methods:This retrospective analysis was conducted on adult CA patients treated with VA-ECMO at Hangzhou First People's Hospital Affiliated to Westlake University School of Medicine, and Second Affiliated Hospital Zhejiang University School of Medicine, from December 2018 to February 2024. General clinical data and serial serum NSE levels at 24, 48, and 72 h after ECMO initiation were collected. Based on the Glasgow-Pittsburgh Cerebral Performance Category (CPC) at discharge, patients were divided into poor neurological outcome group (CPC 3-5) and good neurological outcome group (CPC 1-2). Differences in serum NSE levels between the two groups were compared. The accuracy of serum NSE levels at three time points in predicting poor neurological outcomes in CA patients was assessed via receiver operating characteristic curves, and the optimal cut-off values were determined by the Youden index. Multivariate logistic regression analysis was performed to determine the relationship between serum NSE levels and poor neurological outcomes. Subgroup analysis was based on age, sex, location of CA, and extracorporeal cardiopulmonary resuscitation (ECPR).Results:A total of 120 eligible CA patients were included, with 88 patients (73.3%) having poor neurological outcomes at discharge. Serum NSE levels at 24, 48, and 72 h after ECMO initiation were higher in the poor outcome group compared to the good outcome group (all P<0.05). The serum NSE level at 72 h had the highest accuracy in predicting poor outcomes, with an area under the curve (AUC) of 0.91 (95% CI: 0.85-0.96), and a cut-off value of 42.0 μg/L. The AUCs for 24 and 48 h were 0.78 (95% CI: 0.69-0.86) and 0.87 (95% CI: 0.80-0.94), with cut-off values of 70.6 μg/L and 64.5 μg/L, respectively. Multivariate logistic regression analysis suggested that the serum NSE level at 72 h was associated with poor outcomes ( P<0.05), and an NSE level >42.0 μg/L was an independent risk factor for poor outcomes ( OR=20.29, 95% CI: 2.90-92.15). Subgroup analysis showed that serum NSE level at 72 h was an independent risk factor for poor neurological outcomes in CA patients aged<60 years old, male or female, out-of-hospital or in-hospital CA, and whether to perform ECPR (all P<0.05). Conclusion:Elevated serum NSE levels at 72 h after VA-ECMO initiation are associated with poor neurological outcomes in CA patients, with the cut-off value of 42.0 μg/L.

Objective:To investigate the protective effect of N-acetylcysteine (NAC) against α-amanitin (α-AMA)-induced liver injury via regulation of mitochondrial dynamic imbalance.Methods:Thirty-two ICR mice were randomly (random number) assigned to four groups ( n = 8 per group): normal control, NAC control, α-AMA poisoning, and α-AMA + NAC treatment group. After modeling, behavioral changes were observed and survival curves were plotted. Liver function markers and oxidative stress indicators were measured using ELISA. Pathological damage in liver tissue was examined, and mitochondrial ultrastructural changes were observed via transmission electron microscopy, followed by mitochondrial injury scoring. Survival rates were analyzed using the Kaplan–Meier method. One-way ANOVA was used for intergroup comparisons, followed by pairwise comparisons. Results:Compared with the control group, α-AMA intoxication significantly reduced survival rates and increased serum ALT and AST levels ( P < 0.05). Liver tissues exhibited disordered hepatic cord arrangement, cytoplasmic loosening, and edema. Mitochondria showed moderate to severe swelling, cristae fragmentation, matrix dissolution, and vacuolation, along with increased injury scores ( P < 0.05). Oxidative markers MDA and ROS were elevated, while antioxidant enzymes SOD and CAT were decreased (all P < 0.05). Mitochondrial activity was impaired, expression of fusion proteins OPA1, MFN1, and MFN2 was downregulated, and fission protein DRP1 was upregulated (all P < 0.05). Compared with the α-AMA group, NAC treatment significantly improved survival, reduced ALT and AST levels ( P < 0.05), alleviated pathological and mitochondrial ultrastructural damage, decreased MDA and ROS, increased SOD and CAT (all P < 0.05), enhanced mitochondrial activity, upregulated OPA1, MFN1, and MFN2, and downregulated DRP1 (all P < 0.05). No significant differences were observed between the normal and NAC control groups. Conclusions:NAC may attenuate α-AMA-induced acute liver injury by maintaining mitochondrial dynamic homeostasis.