Background: Programmed death-ligand 1 (PD-L1) contributes to the immune escape of tumor cells and is a critical target for antitumor immunotherapy. However, the molecular mechanisms regulating PD-L1 expression remain unclear, hindering the development of effective therapies. Here we investigate the role and molecular mechanism of the core clock gene Period2 (PER2) in regulating PD-L1 expression and its role in the combination therapy of oral squamous cell carcinoma (OSCC). Methods: Quantitative real-time PCR, western blotting or immunohistochemistry to detect expression of PER2 and PD-L1 in OSCC tissues and cells. Overexpression and knockdown of PER2 detects the function of PER2. Bioinformatics, immunoprecipitation, GST pull-down, CHX chase assay and western blot and strip to detect the mechanism of PER2 regulation for PD-L1. A humanized immune reconstitution subcutaneous xenograft mouse model was established to investigate the combination therapy efficacy. Results: In OSCC tissues and cells, PER2 expression was reduced and PD-L1 expression was increased, the expression of PER2 was significantly negatively correlated with PD-L1. In vitro and in vivo experiments demonstrated that PER2 inhibited PD-L1 expression and enhanced T-cell-mediated OSCC cell killing by suppressing the IKK/NF-κB pathway. Mechanistically, PER2 binds to heat shock protein 90 (HSP90) through the PAS1 domain and reduces the interaction of HSP90 with inhibitors of kappa B kinase (IKKs), promoting the ubiquitination of IKKα/β and p65 nuclear translocation to inhibit IKK/NF-κB pathway, thereby suppressing PD-L1 expression. In humanized immune reconstitution subcutaneous xenograft mouse model, it was demonstrated that PER2 targeting combined with anti-PD-L1 treatment improved the inhibition of OSCC growth by promoting CD8⁺ T-cell infiltration into the tumor. Conclusions: Our findings reveal the role and mechanism of PD-L1 regulation by PER2 and support the potential clinical application of PER2 targeting in combination with anti-PD-L1 in OSCC immunotherapy.

Peer reviewed article authored by (Deping Sun, Kai Yang, Gang Zheng, et al). Read article or submit your manuscript for publishing.

Objective: This study aimed to determine the prevalence of hearing loss and identify associated risk factors in a Chinese population aged 45 years and older.Study design: This study employed a cross-sectional research design. Data from the 4th wave survey of the China Health and Retirement Longitudinal Study (CHARLS) conducted in 2018 were utilized. Participants were assessed using self-reported questionnaires, and various demographic and comorbidity factors were analyzed to elucidate the risk factors associated with hearing loss.Methods: A total of 17,695 individuals from 10,257 households in 450 villages and urban settlements were included in the study. Hearing loss was assessed through self-reported questionnaires. Risk factors, including demographic characteristics and comorbidities, were analyzed to identify associations with hearing loss.Results: The study population had a hearing loss prevalence rate of 17.9% (n = 3,179). Regional variations were observed, with highest rates in Chongqing (28.67%), Yunnan (25.12%), and Qinghai (24.36%), and lowest rates in Zhejiang (17.71%), Tianjin (10.56%), and Shanghai (9.26%). Age ≥70 was associated with higher risk (OR = 3, p<0.05), while being female was associated with reduced risk (OR = 0.81, p<0.05). Higher education level showed lower risk (OR<1, p<0.05). Non-agricultural workers had lower risk (OR = 0.67, p<0.05). Fewer social activities were correlated with decreased risk (OR = 0.89, p = 0.024). Ethnic minorities had slightly higher risk (OR = 1.23, p<0.05).Conclusion: This study provides valuable insights into the prevalence and risk factors associated with hearing loss in the Chinese population aged 45 years and older. The findings emphasize the importance of early detection and intervention, particularly among older individuals and those residing in specific regions, for effective hearing loss management.

This study examines the association between denture use and all-cause mortality risk among Chinese edentulous elderly, using data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS, 2008–2014 waves). A cohort of 8444 adults aged \(\ge 60\) with complete tooth loss was analyzed, with denture use recorded as a binary variable (yes/no) and mortality verified via follow-up linkages. Missing data were handled via multiple imputation (MICE), and propensity score matching (PSM) balanced covariates between denture users and non-users. Kaplan-Meier survival analysis demonstrated significantly improved survival probabilities among denture users compared to non-users (log-rank p = 0.0033). Multivariate Cox proportional hazards models, after full adjustment for potential confounders, consistently revealed that denture non-users faced a 15.8% higher mortality risk (HR = 1.158, 95% CI 1.082–1.239, P < 0.001). Mediation analyses elucidated potential pathways, identifying BMI as a significant partial mediator (indirect effect = − 0.010, P < 0.001) in the denture-mortality relationship. In contrast, neither dietary diversity (DDS: p = 0.105) nor daily staple food intake (DSFA: p = 0.190) demonstrated significant mediating effects. The robustness of these findings was confirmed through comprehensive sensitivity analyses, including complete-case analysis and evaluation of pre-propensity score matched cohorts, with all approaches yielding consistent results. This study provides robust evidence that denture use is significantly associated with reduced all-cause mortality among edentulous elderly adults, with BMI serving as a key mediating factor in this protective relationship.

Objective. The objective of this study was to design and validate a nomogram of intranasal corticosteroid (INCS) insensitivity for adult patients with allergic rhinitis (AR). Methods. Training and validation datasets comprised randomly divided groups of AR patients diagnosed between 2019 and 2022, with a 7:3 ratio. These patients were categorized according to their INCS insensitivity status, and LASSO and multivariate logistic regression analyses were conducted to identify associated risk factors. These factors were incorporated into a nomogram for predicting INCS insensitivity. The performance of the nomogram was assessed using receiver operating characteristic (ROC) curves, calibration curves, and discrimination techniques. Results. In this study, 313 patients were included, of which 120 (38.3) showed INCS insensitivity. The type of AR, comorbidities, family history of AR, and duration of AR were identified as predictors and incorporated into the nomogram using least absolute shrinkage and selection operator and multivariate logistic regression. The calibration curves showed excellent agreement between predicted and actual probabilities of INCS insensitivity in both the training and validation sets. The area under the curve values observed in the validation set were 0.918 (95 confidence interval, 0.8590.943), and 0.932 (95 confidence interval, 0.8490.953) in the training set, indicating strong performance on both sets. Decision curve analysis showed that the constructed nomogram yielded a net clinical benefit for AR patients. Conclusion. The nomogram constructed from risk predictors of INCS insensitivity in patients with AR demonstrated strong predictive power and enabled clinicians to identify high-risk patients, aiding them in developing an optimal treatment plan for AR.

The study aimed to explore the relationship between tooth count and sleep quality and duration in the elderly, investigating the potential mediating role of temporomandibular joint (TMJ) pain in this relationship. Using data from the China Health and Longevity Longitudinal Survey (CLHLS), a cohort analysis was conducted on 5941 older Chinese adults. Multivariate linear regression and mediation analysis were applied to assess the associations, adjusting for sociodemographic factors, health behaviours, and comorbidities. The participants had a mean natural tooth count of 10.1 (SD = 10.4), a mean sleep quality score of 2.38 (SD = 0.93; lower scores indicate better quality), and a TMJ pain prevalence of 6.93%. Linear regression showed that more natural teeth were associated with better sleep quality (coefficient = -0.0036, P = .012), meaning each additional tooth correlated with a small improvement in sleep quality. TMJ pain was linked to poorer sleep quality (coefficient = 0.2175, P < .001), indicating worse sleep in those with TMJ pain. Mediation analysis revealed that TMJ pain partially mediated the relationship: the indirect effect (average causal mediation effect [ACME] = 0.0004, 95% CI: 0.0002 to 0.0005, P < .001) accounted for 11.5% of the total effect, while the direct effect of tooth count on sleep quality remained significant (ADE = -0.0039, P = .006). More natural teeth are associated with better sleep quality in older adults, and TMJ pain partially mediates this relationship. These findings highlight the importance of oral health (tooth retention and TMJ pain management) in improving sleep quality among older adults, providing new insights for clinical intervention in sleep disorders.