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ObjectiveTo construct an evaluation index system for the development level of county-level chronic disease management centers, providing a basis for evaluating and comparing the construction of these centers. MethodsFocusing on the key points of county-level chronic disease management center construction and combining relevant literature, a candidate index database was constructed. Twenty-nine experts in the field of chronic disease management were selected to conduct two rounds of Delphi consultation to determine the evaluation index system for the development level of county-level chronic disease management centers, and the analytic hierarchy process was used to determine the index weights. ResultsThe active participation rates of experts in the two rounds of Delphi consultation were 90.91% and 96.67%, respectively, with expert authority coefficients of 0.85 and 0.84, and Kendall′s W of 0.15 and 0.20 (both P < 0.001). After two rounds of consultation, a final evaluation index system for the development level of county-level chronic disease management centers was constructed, consisting of 5 dimensions and 45 indicators: organizational management and basic conditions, chronic disease management informatization, county-township collaborative management of chronic diseases, capacity building and quality control of chronic disease management, and quality and effectiveness of chronic disease management. The weights of the 5 dimensions were 0.212 2, 0.180 1, 0.219 4, 0.179 4, and 0.208 9, respectively. ConclusionThe evaluation index system for the development level of county-level chronic disease management centers constructed in this study is reasonable, practical, representative, and instructive, providing a reference basis for evaluating the development level of these centers and key directions for subsequent construction.

BackgroundMost head and neck squamous cell carcinoma (HNSCC) patients are diagnosed at an advanced local stage. While immunotherapy has improved survival rates, only a minority of patients respond durably to targeted immunotherapies, posing substantial clinical challenges. We investigated the heterogeneity of the tumor microenvironment in HNSCC cohorts before and after immunotherapy by analyzing single-cell RNA sequencing (scRNA-seq) data and bulk RNA sequencing datasets retrieved from public databases.MethodsWe constructed a single-cell transcriptome landscape of HNSCC patients before and after immunotherapy and analyzed the cellular composition, developmental trajectories, gene regulatory networks, and communication patterns of different cell type subpopulations. Additionally, we assessed the expression levels of relevant indicators in HNSCC cells via western blot, ELISA, and fluorescent probe techniques.ResultsAt the single-cell level, we identified a subpopulation of TP63+ SLC7A5+ HNSCC that exhibited a ferroptosis-resistant phenotype. This subpopulation suppresses ferroptosis in malignant cells through the transcriptional upregulation of SLC7A5 mediated by high TP63 expression, thereby promoting tumor growth and resistance to immunotherapy. The experimental results demonstrated that the overexpression of TP63 upregulated the expression of SLC7A5 and suppressed the concentrations of Fe2+ and ROS in HNSCC cells. By integrating bulk transcriptome data, we developed a clinical scoring model based on TP63 and SLC7A5, which are closely associated with tumor stage, revealing the significant prognostic efficacy of the TP63+ SLC7A5+ HNSCC-mediated ferroptosis mechanism in HNSCC patients.ConclusionOur research elucidates the TME in HNSCC before and after immunotherapy, revealing a novel mechanism by which TP63+ SLC7A5+ HNSCC inhibits ferroptosis and enhances tumor resistance via TP63-induced SLC7A5 upregulation. These insights lay the foundation for the development of more effective treatments for HNSCC.

Background: Head and Neck Squamous Cell Carcinoma (HNSCC) is a malignancy characterized by a high incidence and recurrence rate. 5-methylcytosine (m5C) RNA modification is a common alteration affecting cancer progression; however, how m5C operates within the tumor microenvironment of HNSCC remains to be elucidated. Methods: We conducted Nanopore sequencing on 3 pairs of cancer and paracancerous tissues from mid- and late-stage HNSCC, obtaining 132 upregulated genes (transcriptomically upregulated, m5C elevated) and 129 downregulated genes (transcriptomically downregulated, m5C reduced). Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed; a differential gene interaction network (PPI) was constructed, revealing the interactions of each gene with others in the network. Co-expression analysis was performed on the genes within the PPI, unveiling their expression and regulatory relationships. Through GSVA analysis, variations in related pathways under different states were identified. Furthermore, results of m5C in lncRNA were screened, followed by target gene prediction. Results: Sequencing results from the 3 pairs of mid- and late-stage HNSCC cancer and paracancerous tissues demonstrated that RPS27A, RPL8, and the lncRNAs including differentiation antagonizing nonprotein coding RNA (DANCR), DCST1 antisense RNA 1 (CCDC144NL-AS1), Growth Arrest-Specific Transcript 5 (GAS5), Nuclear Paraspeckle Assembly Transcript 1 (NEAT1), and Small Nucleolar RNA Host Gene 3 (SNHG3), etc., under m5Cregulation, have close connections with surrounding genes. The differentially m5Cmodified genes are primarily involved in ribosomal protein synthesis, oxidative stress response, metabolic reprogramming, immunity, and other life processes; pathways like mitochondrial protein import and photodynamic therapy induced unfolded protein response are upregulated in the tumor, while pathways, including the classic P53, are suppressed. Analysis on m5C-regulated long non-coding RNAs (lncRNAs) revealed tight associations with RPS27A and RPL8 as well. Conclusion: Our study identifies the key factors and signaling pathways involving m5C in HNSCC. The findings suggest that ribosome-related genes might regulate ribosomal protein synthesis, oxidative stress response, metabolic reprogramming, and immune response through m5C RNA modification by means like hypoxia and ferroptosis, thereby playing a pivotal role in the onset and progression of HNSCC. Hence, attention should be paid to the role of ribosomes in HNSCC. These findings may facilitate the precision and individualized treatment of patients with mid- and late-stage HNSCC in clinical settings.

To improve the construction performance and seismic resilience of precast reinforced-concrete frame structures, an innovative self-centering precast steel–concrete hybrid frame has been proposed and subjected to cyclic loading tests. In this paper, a comprehensive numerical analysis was conducted to further investigate the frame’s hysteretic behavior. Initially, a numerical model was developed using the finite element software OpenSees. Numerical analyses of two frame specimens were conducted, demonstrating good agreement between the numerical and experimental hysteretic characteristics, thus validating the model’s accuracy. Subsequently, based on the numerical simulations, a quantitative comparison of hysteretic performance between a novel frame and a traditional reinforced-concrete frame of the same scale was performed. While the proposed frame exhibited slightly lower initial stiffness and energy dissipation capacity than the traditional frame, it outperformed in terms of load-carrying capacity and self-centering ability. Finally, parametric analyses were carried out to assess the influence of various design parameters on the hysteretic performance, including friction force in the web frictions devices, initial post-tensioned force of the prefabricated steel–concrete hybrid beams, the steel arm length, and the column longitudinal reinforcement ratio. The results showed that increases in these four parameters improved the load-carrying capacity and initial stiffness of the proposed frame. Additionally, an increase in the friction force, steel arm length, or column longitudinal reinforcement ratio enhanced the frame’s energy dissipation capacity, while an increase in the initial post-tensioned force or a decrease in the friction force enhanced the frame’s self-centering capacity.

Steel beam–column connections with dog-bone beam sections have gained significant attention and have been extensively applied. This is attributed to their ability to effectively centralize and integrate plastic hinges, thereby diverting potential damage away from the beam ends during earthquake events. In order to achieve the enhancement of the ductility and energy dissipation of connections by inhibiting local buckling during an earthquake event, a novel steel moment connection with buckling-restrained dog-bone beam sections was proposed in this paper. There were three types of proposed connections according to the different arrangements of restrained steel plates, including arranging the restrained plates only on the flanges, only on the web, and on both the flanges and webs of the dog-bone beam sections. In this study, three specimens with buckling-restrained dog-bone beam sections and one control specimen with a dog-bone beam section were tested under cyclic loading. The failure modes, hysteretic curves, skeleton curves, stiffness degradation ductilities, displacement ductility ratios, and energy dissipation capacities of the specimens were analyzed based on the experimental results to evaluate the seismic behavior of the proposed connections. The results indicated that the local buckling of the proposed connections was significantly reduced compared with the traditional connection with a dog-bone beam section under the condition of keeping the plastic hinges away from the beam–column connection core. The arrangement of the restrained plates in the dog-bone beam section had little effect on the bearing capacity and the initial stiffness, with errors all being within 6%. It is worth mentioning that the connection with restrained plates only on the flanges in the dog-bone beam sections showed a more obvious improvement in the deformation capacity and energy dissipation capacity of the connection, which increased by 21% and 16%, respectively. Additionally, high-quality welding between the beam and column, smooth cutting shapes on the weakened flanges, and the high-quality drilling of long slots at the fixed point in the restrained plates and the dog-bone beam sections should be guaranteed to improve the hysteretic stabilities of the proposed connections.

This paper is about the existence of traveling wave solutions for a delayed nonlocal dispersal SIR epidemic model with the critical wave speed. Because of the introduction of nonlocal dispersal and the generality of incidence function, it is difficult to investigate the existence of critical traveling waves. To this end, we construct an auxiliary system and show the existence of traveling waves for the auxiliary system. Employing the results for the auxiliary system, we obtain the existence of traveling waves for the delayed nonlocal dispersal SIR epidemic model with the critical wave speed under mild conditions.