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.

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.

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.

Hearing loss has become increasingly prevalent and causes considerable disability, thus gravely burdening the global economy. Irreversible loss of hair cells is a main cause of sensorineural hearing loss, and currently, the only relatively effective clinical treatments are limited to digital hearing equipment like cochlear implants and hearing aids, but these are of limited benefit in patients. It is therefore urgent to understand the mechanisms of damage repair in order to develop new neuroprotective strategies. At present, how to promote the regeneration of functional hair cells is a key scientific question in the field of hearing research. Multiple signaling pathways and transcriptional factors trigger the activation of hair cell progenitors and ensure the maturation of newborn hair cells, and in this article, we first review the principal mechanisms underlying hair cell reproduction. We then further discuss therapeutic strategies involving the co-regulation of multiple signaling pathways in order to induce effective functional hair cell regeneration after degeneration, and we summarize current achievements in hair cell regeneration. Lastly, we discuss potential future approaches, such as small molecule drugs and gene therapy, which might be applied for regenerating functional hair cells in the clinic.
Infant, Newborn ; Humans ; Hair Cells, Auditory, Inner/physiology* ; Ear, Inner/physiology* ; Hair Cells, Auditory/physiology* ; Regeneration/genetics* ; Stem Cells

Objective To investigate whether modification with IL-21 and CCL19 enhances killing and tumor-infiltrating efficiency of NKP30 CAR-T cells in lung cancer.Methods The modified IL-21-CCL19 NKP30 CAR-T cells expressing IL-21 and CCL19 fusion gene was constructed based on NKP30 CAR-T cells and stimulated with CD3CD28 antibodies and IL-2.The immunophenotype and migration of the cells in the presence of IL-21 were investigated using flow cytometry and migration experiments.Lactate dehydrogenase(LDH)release and sphere formation assays were used to assess the killing and infiltration capabilities of CAR-T cells,and the secretion levels of IFN-γ,IL-21 and CCL19 were determined with enzyme-linked immunospot assay(ELISPOT)and ELISA.A zebrafish model bearing HCG-27 cell xenograft was established by microinjection of the tumor cells into the yolk sac followed 24 h later by injection of the immune cells at the same site,and the fluorescence signals were captured using a fluorescent microscopy.Results The NKP30 ligand B7H6,which was almost undetectable in normal tissues and blood cells,was highly expressed(over 90%)in lung cancer cells.Compared with NKP30 CAR-T cells and conventional T cells,IL-21-CCL19 NKP30 CAR-T cells exhibited stronger proliferative and migration capabilities with the formation of central memory T cells.The reduced expressions of CTLA4 and PD1 in the constructed cells resulted in enhanced killing efficiency against lung cancer cells accompanied by significantly increased production of IFN-γ,IL-21 and CCL19.In the zebrafish models,CAR-T cells exhibited stronger cytotoxicity and proliferative abilities than typical T cells,but these differences were not statistically significant between the two CAR-T cells.Conclusion Modification of NKP30 CAR-T cells with IL-21 and CCL19 facilitates their access into solid tumors for more effective tumor cell killing while producing a large number of memory T cells.

A public hospital Party branch,in the establishment of the"Four Orientations"project(Leading groups work effectively,Party branches work with promising methods,Party building achieves a fame with brand,and each unit has its own model)and"Four Strengths"(strong political role,strong Party branch team,strong team of Party members,and strong per-formance)has combined its work with bold exploration at the intersection of party building and discipline development.The branch has refined a distinctive"Bridge Culture"concept,symbolizing its identity,and has implemented four key projects:"Building bridges""Consolidating bridges""Expanding bridges"and"Preserving bridges".Collectively,these initiatives have led to the development of a"Bridge Culture"brand.The branch's role,as a vanguard in discipline advancement and public health services,has been fully leveraged,aiming to drive high-quality development of discipline through the vehicle of ideological and political work.

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.