Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Objective To analyze the risk factors for cough variant asthma (CVA) and investigate the influence of indoor environment on CVA. Methods From July 2021 to August 2024, 315 patients admitted to the hospital due to CVA were selected as the CAV group. Meanwhile, 100 healthy individuals were selected as the control group. Clinical data of all subjects were collected. Univariate analysis and multivariate logistic regression analysis were used to identify the influencing factors of CVA. Results The proportions of subjects with family history and recurrent respiratory tract infection in the CVA group were higher than those in the control group (P<0.05). The CVA group had significantly higher rates of indoor renovation, mold growth, infrequent bedding cleaning, opening window for ventilation once to 3 times a week, keeping pets, and passive smoking compared to the control group within one year, and the differences were statistically significant (P<0.05). Multivariate logistic regression analysis results showed that indoor-decoration in the past year (OR=2.282, 95%CI: 1.1454.549), mould growth (OR=2.036, 95%CI: 1.228-3.376), opening window for ventilation once to 3 times a week (OR=1.895, 95%CI: 1.253-2.865), seldom cleaning bedding (OR=2.257, 95%CI: 1.132-4.499), keeping pets (OR=2.071, 95%CI: 1.146-3.743), and passive smoking (OR=2.208, 95%CI: 1.377-3.541) were independent risk factors for CVA (P<0.05). Conclusion There is a significant correlation between the occurrence of CVA and indoor environment. Changes in indoor environment include indoor-decoration in the past year, mould growth, low frequency of opening window for ventilation, low frequency of bedding cleaning, keeping pets and passive smoking which are risk factors for the occurrence of CVA.

ObjectiveTo study the relationship between qi stagnation constitution and suboptimal health status (SHS) or lifestyle.MethodsFrom 2012 to 2013, we conducted a cross-sectional survey of 24 159 Chinese individuals aged 12–80 years. The qi stagnation constitution was assessed using the Constitution in Chinese Medicine Questionnaire. Health status was evaluated through medical records and the Subhealth Measurement Scale V1.0 (SHMS V1.0). Health-promoting lifestyles were measured using the Health-Promoting Lifestyle Profile II (HPLP-II).ResultsOf the 24 159 participants, 16.1% and 15.2% were classified as “always” and “sometimes” having the qi stagnation constitution, respectively. Those classified as “rarely” having the qi stagnation constitution scored higher on both the HPLP-II and SHMS V1.0. The participants classified as “always” having the qi stagnation constitution showed a significant association with SHS or disease compared to other imbalanced constitutions. Those in the “always” category were approximately 21 times more likely to be classified as having SHS (odds ratio [OR]: 21.17, 95% confidence interval [CI]: 15.74–28.45), whereas those in the “sometimes” category were approximately six times more likely (OR: 5.89, 95% CI: 5.04–6.90). Accordingly, the qi stagnation constitution score was significantly associated with the diagnosis of SHS, with an area under the curve of 0.77 (P .001). A score of 18.75 yielded the highest Youden Index (0.407), with a sensitivity of 60.5% and a specificity of 80.3%. Significant associations were observed between health-promoting lifestyles and qi stagnation constitution severity in an ordinal regression analysis (P .001). Protective factors included stress management (OR: 1.59), self-actualization (OR: 1.57), and exercise (OR: 1.36). In contrast, poorer interpersonal relationships (OR: 0.79), greater health responsibilities (OR: 0.86), and poorer nutrition (OR: 0.91) were associated with increased severity.ConclusionModulating the qi stagnation constitution through lifestyle interventions may help prevent the progression of SHS to disease, which aligns with core preventive principles in traditional Chinese medicine.

OBJECTIVES: This study aims to explore the potential relationships of cell-free DNA (cfDNA) in gingival crevicular fluid (GCF) with periodontal clinical indicators and the expression of DNA receptor pathway cyclic guanosine phosphate-adenosine phosphate synthase (cGAS)-stimulator of interferon genes (STING) in gingival tissues and human gingival fibroblasts (HGFs). METHODS: GCF and gingival tissue samples were collected from periodontally healthy individuals and patients diagnosed with periodontitis. Periodontal clinical indicators were recorded, including plaque index (PLT), bleeding index (BI), probing depth (PD), and clinical attachment level (CAL). The concentration of cfDNA in GCF was quantified, and the correlation between GCF and periodontal clinical indicators was analyzed. Immunofluorescence and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) were used to assess the distribution of cGAS, STING, and p-STING in gingival tissues. Additionally, the mRNA expression levels of the key components of the cGAS-STING signaling pathway, namely, cGAS, STING, inhibitory of kappa-B kinase (IKK), nuclear factor kappa-B p65 (NF-κB p65), interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α), were measured. Furthermore, cfDNA extracted from GCF was employed to stimulate HGFs in the healthy control and periodontitis groups, and the mRNA expression levels of the key molecules of cGAS-STING signaling pathway were detected through Western blot and RT-qPCR. RESULTS: The concentration of cfDNA in GCF was found to be significantly elevated in the periodontitis group compared with the control group. Moreover, cfDNA concentration demonstrated a strong positive correlation with the periodontal clinical indicators. Immunofluorescence analysis revealed considerably increased percentage of fluorescence co-localization of cGAS, STING, and p-STING with the gingival fibroblast FSP-1 marker in the gingival tissues of the periodontitis group. The mRNA expression levels of cGAS, STING, IKK, NF-κB p65, IL-1β, IL-6,and TNF-α were significantly higher in the periodontitis group. In vitro stimulation of HGFs with GCF-derived cfDNA resulted in increased protein expression of cGAS and p-STING and considerably upregulated the mRNA expression levels of cGAS, STING, IKK, NF-κB p65, IL-1β, IL-6, and TNF-α in the healthy and periodontitis groups compared with the blank group. Correlation analysis showed that the concentration of cfDNA at the sampling site was positively correlated with the mRNA expression levels of cGAS, STING, NF-κB p65, and IL-6 in gingival tissues. CONCLUSIONS cfDNA concentrations in the GCF of patients with periodontitis are considerably elevated, and are associated with the activation of the cGAS-STING signaling pathway in HGFs. These findings suggest that cfDNA contributes to the progression of periodontitis.
Humans ; Gingival Crevicular Fluid/metabolism* ; Signal Transduction ; Gingiva/cytology* ; Nucleotidyltransferases/genetics* ; Membrane Proteins/genetics* ; Cell-Free Nucleic Acids/analysis* ; Fibroblasts/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Periodontitis/metabolism* ; Interleukin-1beta/metabolism* ; Interleukin-6/metabolism* ; Adult ; RNA, Messenger/metabolism* ; Male ; Female

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Objective The progressive loading process of implants was simulated,and the influence of progressive loading method on peri-implant bone reconstruction was evaluated.Methods Using finite element analysis combined with the ANSYS parametric design language(APDL),the average bone density of the peri-implant regions was observed using conventional loading(control group)and progressive loading(experimental group)within six months of implant placement.The stress distributions of bone tissues in a 1 mm3 region of interest(ROI)around the implant and variations in bone density were observed.Results Within six months after implantation,the cortical bone density of the control group decreased by 0.19 g/cm3,whereas that of the experimental group decreased by 0.15 g/cm3.The trabecular bone density of each area in the experimental group increased by 0.4 g/cm3 compared with that in the control group.The bone density in the experimental group was lower than that in the control group.The increase in cancellous bone in the experimental group was higher than that in the control group.The finite element analysis revealed that the equivalent stress distribution range and maximum value of the experimental group(8.9 MPa)were significantly higher than those of the control group(6.68 MPa).Conclusions The use of the progressive loading method within six months after implantation was conducive to the distribution of stress on the bone tissues around the implant.This reduced the variation in bone density at the edge of the implant.The peri-implant bone density increased more under progressive loading than under conventional loading.The effect is superior to that of the conventional loading method.

To enhance the spatial resolution of vibro-acoustography,an improved vibro-acoustography system is constructed using a large-angle dual-frequency focused transducer.Based on this system,mimicking phantoms are used as the experimental objects to explore the spatial resolution of vibro-acoustography,and test the vibro-acoustography results of mimicking phantoms with different acoustic characteristics.Additionally,the effects of the position of hydrophone and difference frequency on the vibro-acoustography results are studied,and the effects of transducer component distribution on vibro-acoustography results are analyzed with a simulation model established with k-Wave.The research results indicate that the vibro-acoustography system with a large-angle dual-frequency focused transducer has higher spatial resolution,contrast and specificity in imaging mimicking phantoms with different acoustic characteristics.The choice of difference frequency is critical for the imaging quality,but the position of the hydrophone and transducer component distribution have trivial effects on vibro-acoustography results.The study is expected to provide new ideas for the development of vibro-acoustography technology,and to promote its further practical application.

Objective:To identify the relationship between the CT arterial radiomics score and the treatment response to neoadjuvant therapy for pancreatic cancer.Methods:The clinical data of 243 pancreatic cancer patients who received surgical resection after neo-adjuvant therapy in the First Affiliated Hospital of Naval Medical University from March 2017 to March 2023 were retrospectively analyzed. Based on the tumor regression grade (TRG), the patients were divided into good response group (TRG 0-1, n=30) and non-good response group (TRG 2-3, n=213). The clinical, radiological and pathological features were compared between two groups. Fully-automated segmentation tool was used for segmenting the arterial CT scan of pancreatic tumor before and after treatment. Python package was applied to extract the radiomics features of tumors after segmentation and the extracted features were reduced and chosen using the least absolute shrinkage and selection operator (Lasso) logistic regression algorithm. Lasso logistic regression formula was applied to calculate the arterial radiomics score. Univariate and multivariate logistic regression models were used to analyze the association between arterial radiomics score and treatment response to neoadjucant therapy. Receiver operating-characteristics (ROC) curve was drawn and area under curve (AUC), specificity, sensitivity and accuracy for evaluating the treatment response were calculated. The clinical usefulness of arterial radiomics score for diagnosing the response of neoadjuvant treatment for pancreatic cancer were determined by decision curve analysis (DCA) . Results:A total of 330 arterial radiomics CT features were obtained, and 9-selected arterial phase features associated with treatment response were determined after being reduced by the Lasso logistic regression algorithm. Univariate analysis showed that the arterial radiomics score, three-dimensional diameter after neoadjuvant therapy, pancreatic contour, T stage, N stage, Peri-pancreatic nerve invasion, lymph-vascular space invasion (LVSI) and invasion of duodenum were all associated with treatment response (all P value <0.05). Multivariate logistic regression analyses confirmed that arterial radiomics score was obviously associated with the neoadjuvant treatment response ( P<0.001). At the cut-off value of 1.93, AUC of the arterial radiomics score for diagnosing neoadjuvant treatment response was 0.92, and the specificity, sensitivity and accuracy was 86.7%, 84.5% and 84.8%. DCA demonstrated that when the percentage for predicting the treatment response by using the arterial radiomics score was >0.2, the patients could benefit from the application of arterial radiomics score for evaluating neoadjuvant therapy response. Conclusions:The arterial radiomics score was strongly correlated with the neoadjuvant treatment response of pancreatic cancer, and can accurately predict neoadjuant treatment efficacy.

Objective A porcine vocal cord injury model was established to analyze and compare the damage range of porcine vocal cords and the repair process after vocal cord injury caused by CO2 laser surgery and radiofre-quency ablation with plasma spot excitation technology.Methods Fifteen pigs,30 sides of vocal cords,were used in this study.The bilateral vocal cords of the same pig were divided into CO2 laser and radiofrequency coblation(RFC)groups respectively.CO2 laser and radiofrequency ablation with plasma spot excitation technology were used to perform ubligamental cordectomy.Three pigs were sacrificed after anesthesia on postoperative day 1 and postop-erative 3,6,9,and 15 weeks.The vocal cords were harvested for HE staining.The depth of edema degeneration zone and the fibrous tissue thickness were measured vertically in the two groups,and the postoperative vocal cord damage range and vocal cord repair process were compared between the two groups.Results The depth of edema degeneration zone in the CO2 laser group was deeper than that in the RFC group at 1 day postoperatively(P＜0.01).There was no significant difference in the depth of the edema degeneration zone between the two groups at the 3rd,6th,and 9th weeks after operation(P＞0.05).The depth of the edema degeneration zone at 3rd weeks postoperatively was less than that at 1 day postoperatively,and at 6th weeks postoperatively was less than that at 3rd weeks postoperatively for both operation modes(P＜0.05).There was no statistically significant difference be-tween 9th weeks postoperatively and 6th weeks postoperatively(P＞0.05).At the 15th week after operation,the fibrous tissue thickness of the vocal fold lamina propria in the RFC group was thinner than that in the CO2 laser group(P＜0.01).Conclusion Radiofrequency ablation with plasma spot excitation technology causes less damage to porcine vocal fold than CO2 laser.There is no significant difference between the two operation modes in terms of postoperative repair process,while the fibrous tissue in the lamina propria of the vocal fold is thinner in the RFC group when a vocal fold scar is formed.