The NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, a high-molecular-weight protein complex in the cytoplasm, is composed of three core components: the sensor protein NLRP3, the adaptor protein apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) and the effector protein caspase-1. It plays a critical role in regulating host immune and inflammatory responses. Studies have shown that the NLRP3 inflammasome has increasingly become a focal point in tumor molecular biology field. A growing body of evidence indicates that the increased expression and activation of the NLRP3 inflammasome is closely associated with the pathogenesis of head and neck squamous cell carcinoma (HNSCC) and the tumor microenvironment (TME). It may promote tumor proliferation, invasion, migration, and other biological behaviors through various regulatory mechanisms while influencing tumor immune evasion and therapy resistance, which holds promise as a prognostic biomarker for patients. This review explores the current effect and mechanism of the NLRP3 inflammasome and its signaling pathways in head and neck cancer, providing insights into clinical targeted drug development and molecular immunotherapy.
Humans ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Inflammasomes/metabolism* ; Head and Neck Neoplasms/pathology* ; Squamous Cell Carcinoma of Head and Neck/metabolism* ; Tumor Microenvironment ; Signal Transduction ; Animals

Objective:To investigate the impact of four registration methods on the accuracy of virtual occlusal records (VOR) in intraoral scanning for implant restorations with multiple missing teeth.Methods:A mandibular model simulating clinical conditions with multiple missing teeth (right first molar, left second premolar, left first molar, left second molar) and a maxillary compete dentition model were mounted on a semi-adjustable articulator. Subsequently, twelve 0.5 mm stainless steel spheres were adhered to reference positions (16, 46, 13, 43, 23, 33, 25, 35, 26, 36, 27, 37) as fiducial markers. Following this, a laboratory scanner generated reference datasets by digitizing the models in maximum intercuspation (MIP). Meanwhile, ten maxillary and mandibular scans were acquired using an intraoral scanner, with all nonarticulated scans duplicated four times to ensure data consistency. Forty VOR intraoral scans were performed in MIP using four registration protocols: left-side, right-side, anterior, and bilateral registration ( n=10 per group), randomized via a computer-generated pseudo-random sequence. For measurement, linear distances (D16-46, D13-43, D23-33, D25-35, D26-36, D27-37, D16-46 represented the single-tooth defect position, whereas D25-35, D26-36, D27-37 reflected positions in free-end edentulism areas) between opposing markers were measured in a reverse engineering software, with deviations (ΔD) from the reference scan calculated to assess accuracy. Specifically, negative ΔD values indicated vertical dimension underestimation. Given that non-normally distributed data were analyzed using medians [interquartile ranges (IQR)], trueness (median ΔD) and precision (IQR) were evaluated. The interaction effect between the registration method and the position of the measurement items was evaluated by using the generalized linear model. The accuracy was compared overall by the Kruskal-Wallis test with the two-sided significance level of α=0.05. For pairwise comparisons, post-hoc tests were conducted by Dunn′s t-test with the Bonferroni correction for the significance level. Results:The accuracy of VOR was affected by registration method ( P<0.05), with a significant position×registration method interaction observed ( P<0.05). In particular, in all four groups, only the bilateral registration group showed trueness of less than 0.1 mm for both free-end edentulism and the single tooth defect, with ΔD16-46, ΔD25-35, ΔD26-36, and ΔD27-37 being 0.059 (0.015), -0.082 (0.052), -0.065 (0.032), -0.070 (0.050) mm, respectively. Moreover, trueness in free-end edentulism showed negative values across all groups, with the largest negative deviations observed in the right-side registration group, with ΔD25-35, ΔD26-36 and ΔD27-37 being -0.410 (0.174), -0.442 (0.225), -0.439 (0.262) mm, respectively. Conclusions:In fully digital workflows of implant restorations for mandibular free-end edentulism with multiple missing teeth, registration method critically influences VOR accuracy. While four registration methods exhibited underestimation of occlusal vertical dimension, bilateral registration achieved the highest accuracy.

Objective To develop and translate the Chinese listening self-efficacy questionnaire(C-LSEQ)and to test its reliability and validity.Methods A total of 172 subjects aged≥60 years with age-related hearing loss completed the C-LSEQ questionnaire via direct interviews.Pure tone hearing threshold test,Mandarin hearing in noise test,and the hearing handicap inventory for elderly-screening(HHIE-S)were evaluated.Twenty subjects were randomly selected from the original group to complete the C-LSEQ questionnaire in 2 weeks after the initial evaluation.Results ① Reliability:The Cronbach's a coefficients of the three sub-dimensions and the overall ques-tionnaire were all＞0.8,and the test-retest reliability coefficients of the three sub-dimensions and the overall ques-tionnaire were all＞0.9(P＜0.001).② Validity:The experts collectively evaluated the representativeness of the statements with good content validity.The convergent validity test showed that the composite reliability(CR)of the 2 sub-dimensions and the overall questionnaire were all＞0.7,and the average variance extracted(AVE)were all＞0.5.The CR value of the complex listening dimension was 0.655,and the AVE value was 0.937.The criterion validity test showed that the overall questionnaire and the three sub-dimensions of the C-LSEQ were significantly correlated with the pure-tone average,speech recognition thresholds in noise,and HHIE-S(P＜0.001).Conclusion The C-LSEQ exhibits stable structure,with good reliability and validity.It can be used to assess listen-ing self-efficacy in adults with hearing loss,especially in the elderly with age-related hearing loss.

Objective To establish a human luminal breast cancer stem cell(BCSC)model and investigate the inhibitory effects of astragaloside Ⅳ(AS-Ⅳ)on BCSC growth.Methods MCF-7 breast cancer cells were cultured in stem cell-specific medium to induce BCSC formation.The BCSCs were then divided into a blank control group and an AS-Ⅳ treatment group,both groups were given PBS or AS-Ⅳ treatment.Morphological changes were observed after intervention.The therapeutic efficacy of AS-Ⅳ was evaluated using 3D spheroid formation and cell viability assays.Transcriptomic profiling and gene expression analysis were performed to elucidate the underlying mechanisms.Results Compared with the MCF7 breast cancer cells,MCF7 breast cancer stem cell mammospheres exhibited accelerated growth(P＜0.01)and significantly increased expression of the stemness marker ALDH1A1(P＜0.01).Further comparison with the blank control group revealed that astragaloside Ⅳ(AS-Ⅳ)treatment significantly inhibited MCF7 breast cancer stem cell proliferation(P＜0.001)and slowed mammosphere growth(P＜0.01).Transcriptomic analysis demonstrated that differentially expressed genes(DEGs)induced by stem cell modeling and AS-Ⅳ intervention were enriched in the cellular senescence signaling pathway.AS-Ⅳ intervention substantially increased the number of SA-β-gal-positive cells(P＜0.01).RT-PCR analysis confirmed that AS-Ⅳsignificantly upregulated mRNA expression of IL-1α(P＜0.01),P21(P＜0.001),and P53(P＜0.05)in MCF7 breast cancer stem cells.Conclusion Astragaloside Ⅳ suppresses the growth of human luminal breast cancer stem cells by inducing cellular senescence.

The aim of this study is to identify the cause of death of a South China tiger cub at the Meihuashan breeding institute of Fujian Province.Pathogenic bacteria were isolated and cultured from liver,spleen,lung and other tissue samples of the dead South China tiger aseptically.The iso-lated bacteria were identified through morphological observation,biochemical characterization,sequence analysis of housekeeping gene gyrB,virulence gene detection,animal pathogenicity test and drug sensitivity test.A pathogenic Aeromonas hydrophila strain,designated FJ/Tiger-201809 was successfully isolated from the trachea of dead South China tiger.The nucleotide sequence ho-mology between the isolate and 11 strains of Aeromonas gyrB ranged from 91.2％to 99.1％,with the highest homology of 99.1％observed with Aeromonas hydrophila(AF208251.1).Genetic evo-lution analysis showed that the isolated strain FJ/Tiger-201809 was in the same evolutionary branch as other reference strains of Aeromonas hydrophila and was closely related.The pathoge-nicity test in mice showed artificial infection of mice with the strain resulted in varying degrees of lesions in several organs of the mice,and the median lethal dose(LD50)was 1 × 107.8 CFU/mL.Virulence gene test results showed that the isolate FJ/Tiger-201809 carried two virulence genes,aer and act.The results of drug sensitivity test showed that FJ/Tiger-201809 was highly sensitive to enrofloxacin and ampicillin among 18 commonly used antibiotics,relatively sensitive to penicil-lin G and doxycycline,and resistant to the other 14 antibiotics.In conclusion,this study isolated and identified a strain of Aeromonas hydrophila from a dead South China tiger with multiple drug resistance and strong pathogenicity,which provided an important reference for the prevention and control of bacterial diseases in South China tiger.

Objective:To explore the factors influencing ethical sensitivity of oncology nurses.Methods:Using purposive sampling, 15 oncology nurses from 13 tertiary general hospitals in Foshan, Guangdong Province were selected as research participants from July to September 2023. In-depth semi-structured interviews were conducted, and Colaizzi's seven-step content analysis method was applied to organize and analyze the collected data.Results:A total of 4 themes were summarized: insufficient clinical experience and knowledge reserve; lack of ethical education and management system processes; high-pressure working environment and communication barriers; and the constraints of the cultural concept of "valuing life over death".Conclusions:Oncology nurses have insufficient ethical sensitivity. Nursing managers should establish a systematic ethical education system, improve ethical management systems, optimize the clinical working environment, and integrate cultural sensitivity education to jointly enhance nurses' communication skills. Attention should also be paid to the inheritance of clinical experience from senior nurses, so as to improve the ethical sensitivity of oncology nurses in a multidimensional way.

Objective:To explore the factors influencing ethical sensitivity of oncology nurses.Methods:Using purposive sampling, 15 oncology nurses from 13 tertiary general hospitals in Foshan, Guangdong Province were selected as research participants from July to September 2023. In-depth semi-structured interviews were conducted, and Colaizzi's seven-step content analysis method was applied to organize and analyze the collected data.Results:A total of 4 themes were summarized: insufficient clinical experience and knowledge reserve; lack of ethical education and management system processes; high-pressure working environment and communication barriers; and the constraints of the cultural concept of "valuing life over death".Conclusions:Oncology nurses have insufficient ethical sensitivity. Nursing managers should establish a systematic ethical education system, improve ethical management systems, optimize the clinical working environment, and integrate cultural sensitivity education to jointly enhance nurses' communication skills. Attention should also be paid to the inheritance of clinical experience from senior nurses, so as to improve the ethical sensitivity of oncology nurses in a multidimensional way.

Objective To investigate the underlying mechanisms contributing to the limited therapeutic efficacy of endocrine therapy combined with CDK4/6 inhibitors in HR+/HER2-low breast cancer,and to develop a breast cancer organoid model as a tool for the precise identification of HR+/HER2-low patients who are responsive to pan-TKI treatment.Methods Transcriptomics was employed to identify differentially expressed genes in HR+/HER2-0 and HR+/HER2-low breast cancer samples and to perform functional enrichment analysis.Tumor organoid models were established using breast cancer tissues obtained from clinical sources,and the differential sensitivity of these samples to therapeutic agents was assessed using Calcein-AM/PI cell viability staining and EdU-based cell proliferation assays.Results The results of transcriptomic enrichment analysis indicated that EGFR was signifi-cantly activated in HR+/HER2-low breast cancer and exhibited characteristics of resistance to TKIs.Breast cancer organoids were successfully established.Drug sensitivity testing revealed that the therapeutic efficacy of ET combined with CDK4/6 inhibitors was suboptimal in certain cases of HR+/HER2-low breast cancer,while the addition of TKIs effectively restored sensitivity to the ET+CDK4/6 inhibitor regimen(P<0.05).Conclusions TKI can restore the reduced sensitivity of HR+/HER2-low breast cancer to endocrine therapy combined with CDK4/6 inhibitors.Breast cancer organoids hold promise as screening tools for assessing drug sensitivity in clinical settings for patients with HR+/HER2-low breast cancer.

Objective To develop and translate the Chinese listening self-efficacy questionnaire(C-LSEQ)and to test its reliability and validity.Methods A total of 172 subjects aged≥60 years with age-related hearing loss completed the C-LSEQ questionnaire via direct interviews.Pure tone hearing threshold test,Mandarin hearing in noise test,and the hearing handicap inventory for elderly-screening(HHIE-S)were evaluated.Twenty subjects were randomly selected from the original group to complete the C-LSEQ questionnaire in 2 weeks after the initial evaluation.Results ① Reliability:The Cronbach's a coefficients of the three sub-dimensions and the overall ques-tionnaire were all＞0.8,and the test-retest reliability coefficients of the three sub-dimensions and the overall ques-tionnaire were all＞0.9(P＜0.001).② Validity:The experts collectively evaluated the representativeness of the statements with good content validity.The convergent validity test showed that the composite reliability(CR)of the 2 sub-dimensions and the overall questionnaire were all＞0.7,and the average variance extracted(AVE)were all＞0.5.The CR value of the complex listening dimension was 0.655,and the AVE value was 0.937.The criterion validity test showed that the overall questionnaire and the three sub-dimensions of the C-LSEQ were significantly correlated with the pure-tone average,speech recognition thresholds in noise,and HHIE-S(P＜0.001).Conclusion The C-LSEQ exhibits stable structure,with good reliability and validity.It can be used to assess listen-ing self-efficacy in adults with hearing loss,especially in the elderly with age-related hearing loss.

Objective:To investigate the impact of four registration methods on the accuracy of virtual occlusal records (VOR) in intraoral scanning for implant restorations with multiple missing teeth.Methods:A mandibular model simulating clinical conditions with multiple missing teeth (right first molar, left second premolar, left first molar, left second molar) and a maxillary compete dentition model were mounted on a semi-adjustable articulator. Subsequently, twelve 0.5 mm stainless steel spheres were adhered to reference positions (16, 46, 13, 43, 23, 33, 25, 35, 26, 36, 27, 37) as fiducial markers. Following this, a laboratory scanner generated reference datasets by digitizing the models in maximum intercuspation (MIP). Meanwhile, ten maxillary and mandibular scans were acquired using an intraoral scanner, with all nonarticulated scans duplicated four times to ensure data consistency. Forty VOR intraoral scans were performed in MIP using four registration protocols: left-side, right-side, anterior, and bilateral registration ( n=10 per group), randomized via a computer-generated pseudo-random sequence. For measurement, linear distances (D16-46, D13-43, D23-33, D25-35, D26-36, D27-37, D16-46 represented the single-tooth defect position, whereas D25-35, D26-36, D27-37 reflected positions in free-end edentulism areas) between opposing markers were measured in a reverse engineering software, with deviations (ΔD) from the reference scan calculated to assess accuracy. Specifically, negative ΔD values indicated vertical dimension underestimation. Given that non-normally distributed data were analyzed using medians [interquartile ranges (IQR)], trueness (median ΔD) and precision (IQR) were evaluated. The interaction effect between the registration method and the position of the measurement items was evaluated by using the generalized linear model. The accuracy was compared overall by the Kruskal-Wallis test with the two-sided significance level of α=0.05. For pairwise comparisons, post-hoc tests were conducted by Dunn′s t-test with the Bonferroni correction for the significance level. Results:The accuracy of VOR was affected by registration method ( P<0.05), with a significant position×registration method interaction observed ( P<0.05). In particular, in all four groups, only the bilateral registration group showed trueness of less than 0.1 mm for both free-end edentulism and the single tooth defect, with ΔD16-46, ΔD25-35, ΔD26-36, and ΔD27-37 being 0.059 (0.015), -0.082 (0.052), -0.065 (0.032), -0.070 (0.050) mm, respectively. Moreover, trueness in free-end edentulism showed negative values across all groups, with the largest negative deviations observed in the right-side registration group, with ΔD25-35, ΔD26-36 and ΔD27-37 being -0.410 (0.174), -0.442 (0.225), -0.439 (0.262) mm, respectively. Conclusions:In fully digital workflows of implant restorations for mandibular free-end edentulism with multiple missing teeth, registration method critically influences VOR accuracy. While four registration methods exhibited underestimation of occlusal vertical dimension, bilateral registration achieved the highest accuracy.