OBJECTIVE Aimed to investigate the impact of comorbid asthma on chronic rhinosinusitis with nasal polyps(CRSwNP)and identify key proteins and signaling pathways.METHODS Proteomic methods were employed to analyze differentially expressed proteins(DEPs)in nasal lavage fluid(NLF)from control,CRSwNP,and CRSwNP with asthma groups.DIA quantitative analysis technology was used to assess the gradient changes of DEPs among the three groups to determine key proteins affected by comorbid asthma in CRSwNP.RESULTS Compared to the control group,1 377 and 1 006 DEPs were identified in the CRSwNP and CRSwNP with asthma groups,respectively.Peroxiredoxin-5(PRDX5),Ran-Binding Protein 1(RanBP1)(upregulated),and Keratin 9(KRT9)(downregulated)were identified as key proteins affecting CRSwNP with asthma.CONCLUSION Comorbid asthma may promote the occurrence and development of nasal polyps through specific key proteins and signaling pathways,providing new molecular insights into the interaction between CRSwNP and asthma.

OBJECTIVE To investigate the expression characteristics and regulatory mechanisms of the circadian clock gene period circadian regulator 1(PER1)and the tumor suppressor gene serine peptidase inhibitor Kazal type 5(SPINK5)in head and neck squamous cell carcinoma(HNSCC),and to elucidate the molecular mechanism by which PER1 regulates SPINK5 transcription via the NF-κB signaling pathway.METHODS Differentially expressed genes in HNSCC were screened using The Cancer Genome Atlas(TCGA)and GSE205155 datasets.The association between SPINK5 expression and patient prognosis was assessed via the GEPIA database.mRNA and protein expression levels of SPINK5 and PER1 in 60 clinical samples were detected by RT-qPCR,immunohistochemistry,and Western blot.PER1 knockdown(using siRNA)and overexpression(via plasmid transfection)were performed in the AMC-HN-8 cell line.Wound healing and colony formation assays were applied to evaluate the effects of PER1,SPINK5,and their interaction on HNSCC cell migration and proliferation.Western blot was utilized to examine the regulatory effect of NF-κB on SPINK5.RESULTS SPINK5 and PER1 were significantly downregulated in HNSCC tissues(all P<0.01),and their low expression was correlated with poor patient prognosis(for SPINK5,HR=0.69,P=0.006 7).A significant positive correlation was observed between PER1 and SPINK5 expression(R2=0.719 2,P=0.001 0).Knockdown and overexpression of PER1 respectively resulted in synchronous alterations in SPINK5 mRNA levels(all P<0.05).PER1 knockdown enhanced cell migration and proliferation(P<0.05),whereas SPINK5 overexpression suppressed these capabilities(P<0.01).Importantly,SPINK5 overexpression reversed the phenotypic changes induced by PER1 knockdown.Mechanistically,PER1 overexpression led to concomitant changes in NF-κB expression,activating the NF-κB pathway and thereby promoting SPINK5 transcription.CONCLUSION PER1 positively regulates SPINK5 transcription via the NF-κB pathway,inhibiting HNSCC cell proliferation and migration.These findings suggest that PER1 and SPINK5 may serve as potential therapeutic targets for HNSCC.

OBJECTIVE To analysis the clinical and pathological characteristics of lymph nodes metastasis in pediatric patients with differentied thyroid carcinoma(pDTC),and to develop a nomogram for predicting lymph nodes metastasis in patients with pDTC.METHODS Four cohorts were integrated in this study,including internal training cohort(1419 cases)and validation cohort(609 cases)from the Surveillance,Epidemiology,and End Results(SEER)database of the National Cancer Institute,TCGA-pDTC cohort(20 cases from the Cancer Genome Atlas Program)and YHD-pDTC cohort(39 cases from true world).The least absolute shrinkage and selection operator(Lasso)and logistic regression were used to screen factors related to lymph nodes metastasis in the presence and exclusion of T stage in pDTCs based on internal training cohort and construct nomograms.Calibration curve,receiver operating characteristic(ROC)curve,area under the ROC curve(AUC)and decision curve analysis(DCA)were used to evaluate model performance in the other three cohorts.RESULTS Multivariate logistic regression results showed that pathology[OR(95%CI):0.020(0.010-0.060),P<0.001],M stage[OR(95%CI):29.550(3.190-273.490),P=0.003],and T stage[OR(95%CI):2.210(1.820-2.680),P<0.001]were independent factors affecting lymph nodes metastasis in pDTCs.Through the internal training set,internal validation set,YHD-pDTC cohort and TCGA-pDTC cohort,the AUC values were 0.734(0.709,0.758),0.752(0.716,0.788),0.969(0.920,1),and 0.600(0.342,0.858)in that order,and the calibration curves are close to the perfect reference line.T stage is a better predictor of lymph nodes metastasis than extraperitoneal intrusion and tumor size.CONCLUSION Pathology,M stage,and T stage are risk factors for predicting lymph nodes metastasis in pDTCs.The nomogram established on this basis can make individualized predictions of the probability of lymph nodes metastasis in pDTCs.

[ABSTRACT]OBJECTIVE To analyze the risk factors for relapse in patients with chronic rhinosinusitis with nasal polyps(CRSwNP)combined with asthm and provide favorable information for precise treatment and healthy prognosis of patients with CRSwNP combined with asthma.METHODS The clinical data of 161 patients with chronic rhinosinusitis with nasal polyps(CRSwNP)combined with asthm who underwent endoscopic surgery at the Department of Otolaryngology Head and Neck Surgery,Yantai Yuhuanding Hospital,affiliated to Qingdao University,from January 2016 to June 2021 were selected.Based on Lasso's Cox regression analysis and multifactorial Cox regression analysis,the associated risk factors were investigated,and the area under curve(AUC)was calculated to determine the performance of the model.Finally,the Kaplan-Meier(K-M)curves were plotted for the relevant influencing factors.RESULTS The Age[HR(95%CI):0.96(0.948-0.98),P<0.001],gender[HR(95%CI):1.94(1.21-3.14),P=0.006],tissue eosinophil percentage[HR(95%CI):1.01(1.01-1.02),P=0.004],and endoscopic nasal polyp score[HR(95%CI):0.86(0.78-0.96),P=0.005]were highly correlated with recurrence in patients with CRSwNP combined with asthma.Patients with CRSwNP combined with asthma had a higher likelihood of relapse after treatment when the tissue Eos%was>21.28%and the endoscopic nasal polyp score was>4.CONCLUSION The age,gender,tissue eosinophil percentage and endoscopic nasal polyp score are independent risk factors for disease recurrence in patients with CRSwNP combined with asthma.

Objective:To analyze the risk factors affecting regional lymph node metastasis in salivary gland mucoepidermoid carcinoma (MEC) and to establish a nomogram model for individually predicting lymph node metastasis in salivary gland MEC.Methods:The clinical data of 2 152 patients with salivary gland MEC from 1975 to 2020 were collected from the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute. The collected data were divided into training cohort (1 506 cases) and validation cohort (646 cases) according to the ratio of 7∶3. Single-factor regression and multi-factor logistic regression were used to screen factors related to local lymph node metastasis in salivary gland MEC, with constructing of a nomogram. Calibration curve, receiver operating characteristic (ROC) curve, area under the ROC curve (AUC) and decision curve analysis were used to evaluate model performance in the validation cohort and the total cohort. Statistical tests were performed using SPSS (26.0) and R (4.3.0) software.Results:Multivariate logistic regression results showed that M stage [ OR(95% CI):12.360(3.295-46.365), P=0.014], pathological grade Ⅱ、Ⅲ、Ⅳ[ OR(95% CI): 1.956(1.329-2.879), 9.654(6.309-14.772), 9.298(6.072-14.238), P<0.001], T staging T2, T3, T4[ OR(95% CI): 1.706(0.932-3.124), 3.021(1.790-5.096), 3.311(1.925-5.695), P<0.001], and gender [ OR(95% CI):0.759(0.593-0.972), P=0.029] were independent factors affecting local lymph node metastasis in salivary gland MEC. Through verification in the validation cohort and the total cohort, the AUC values were greater than 0.8, and the calibration curve was close to the perfect reference line, proving that the constructed nomogram model had good specificity and sensitivity for predicting local lymph node metastasis in salivary gland MEC. Conclusion:M stage, pathological grade, T stage, and gender are risk factors for predicting regional lymph node metastasis and the established-nomogram has good predictive performance for local lymph node metastasis in salivary gland MEC.

Objective:To identify potential therapeutic targets of chronic sinusitis with nasal polyps (CRSwNP) through proteomics screening of and verify its effectiveness experimentally.Methods:The nasal tissue samples were collected from patients undergoing surgical treatment in the Department of Otorhinolaryngology, Head and Neck Surgery in Yuhuangding Hospital of Yantai from June 2010 to December 2021, including 69 patients with CRSwNP and 39 patients in the control group. Tissue samples were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in data-independent acquisition (DIA) mode to find differentially expressed proteins. Bioinformatics tools were employed to analyze the functions of differentially expressed proteins. The expression of hematopoietic cell kinase (HCK) in nasal tissues of patients with CRSwNP was further confirmed by qPCR and western blot. The mouse model of CRSwNP was established and treated with HCK inhibitor. The levels of inflammatory factors IgE, IL-4 and IL-5 in serum of CRSwNP mice, both treated and untreated with HCK inhibitors, were detected by enzyme-linked immunosorbent assay (ELISA) across different experimental groups. The experimental data were analyzed by Graphpad Prism 9 software.Results:DIA analysis identified 1 850 differential proteins, including 760 up-regulated proteins and 1 090 down-regulated proteins. Weighted correlation network analysis (WGCNA) correlation analysis of phenotypic data such as cell count and CT score with the results of genomics indemnified 575 proteins of MEBrown module which intersected with 35 kinases further screened from 1 850 differential proteins, yielding eight protein kinases: HCK, SYK, PDK2, FGR, PRKCB, ROR1, CAMK1 and GRK6. qPCR showed that the expression of HCK in CRSwNP was significantly higher than that in the control group ( P<0.05). Further experiments in mice confirmed that the secretion of IgE, IL-4 and IL-5 in the serum of CRSwNP group was significantly higher than the control group (all P<0.05), indicating successful model establishment. The intervention of HCK significantly decreased the secretion of IgE, IL-4 and IL-5 in serum of mice (all P<0.05). Conclusion:The HCK inhibitor can reduce the inflammatory index of mice with CRSwNP, and HCK is a potential therapeutic target of CRSwNP.

OBJECTIVE To explore the independent factors affecting tissue inflammatory cells changes in recurrent nasal polyps.METHODS The clinical data of 31 patients with nasal polyps who underwent endoscopic surgery at the Department of Otolaryngology Head and Neck Surgery,Yantai Yuhuanding Hospital from December 2007 to December 2021 were selected and analyzed by stepwise regression logistic analysis.RESULTS The number of tissue inflammatory cells in recurrent nasal polyps changed compared with that in primary nasal polyps,and the number and percentage of neutrophils in recurrent polyps increased(P<0.05).Logistic analysis revealed that smoking was an independent risk factor for eosinophilia in recurrent nasal polyps,increasing age was an independent factor for lowering neutrophils,and the comorbid allergic rhinitis and the time interval of recurrence were independent factors for lowering and increasing lymphocytes,respectively.CONCLUSION The number of tissue-infiltrating cells is altered in recurrent polyps compared with primary polyps.Smoking is an independent risk factor for eosinophilia in recurrent polyps.

Objective:To investigate the clinicopathological features and prognostic factors of breast cancer patients with low expression of human epidermal growth factor receptor 2 (human epidermal growth factor receptor-2, HER-2).Methods:Retrospective analysis was made on the clinical data of 823 cases of breast cancer with HER-2 non positive treated by surgery in the First Affiliated Hospital of Bengbu Medical College from January 1, 2013 to December 31, 2016. Collect general clinical indicators (age, site of onset, menstrual status, etc.), pathological features (tumor TNM staging, histological grading, pathological type, axillary lymph node status, Ki-67 index, and expression of HER-2, ER, PR), treatment plans (endocrine therapy, radiotherapy, and chemotherapy plans), survival status (pathological diagnosis time, surgery time, recurrence or metastasis time, and death time). To compare the clinicopathological characteristics of HER-2 non positive breast cancer patients with different hormone receptor status, and analyze the influencing factors of DFS and overall survival. Non normally distributed econometric data are represented by M( Q1, Q3), and Wilcoxon rank sum test is used for comparison between the two groups; Count data is represented as an example (%), and χ 2 test is used for inter group comparison; Use Kaplan Meier method to plot survival curves, and analyze the differences in disease-free survival rate and overall survival rate among different subgroups through Log rank test; Use univariate and multivariate Cox proportional risk models to analyze the influencing factors of prognosis. P<0.05 indicates a statistically significant difference. Results:Among 823 HER-2 non positive breast cancer patients, 657 (79.83%) were hormone receptor positive and 166 (20.17%) were negative; 287 cases (34.87%) had zero expression of HER-2, and 536 cases (65.13%) had low expression. Compared with the hormone receptor negative group, the hormone receptor positive group had a higher proportion of HER-2 low expression (68.49% (450/657) compared to 51.81% (86/166), χ 2=16.25, P<0.001), and a lower proportion of Ki-67>30% (32.57% (214/657) compared to 72.29% (120/166), χ 2=86.69, P<0.001). In the hormone receptor positive group, compared with the HER-2 zero expression subgroup, the HER-2 low expression subgroup had a lower proportion of patients with onset age ≥ 40 years old ( P=0.026), a higher proportion of premenopausal women ( P=0.045), a later pathological stage ( P=0.042), and a lower positive rate of axillary lymph nodes ( P=0.023). Multivariate analysis showed that primary tumor size stage T3-T4, Ki-67 > 30% and HER-2 zero expression were risk factors for 10-year DFS and total survival of hormone receptor positive HER-2 non positive breast cancer patients (10-year DFS: HR values were 2.840, 2.010, 2.652, 95% CI: 2.265－4.010, 1.563－2.471, 1.983－3.441, all P=0.001; Overall survival: HR values were 1.923, 1.954, 95% CI: 1.332－2.642, 1.774－2.531, with P values of 0.041 and 0.012, respectively; Primary tumor size stage T3-T4 and HER-2 zero expression are risk factors for 10-year DFS in hormone receptor negative HER-2 non positive breast cancer patients ( HR values are 2.096 1.885, 95% CI: 1.687－3.000, 1.452－2.774, P values are 0.026 and 0.005, respectively). Regional lymph node stage N1-N3 is a risk factor for 10-year overall survival ( HR=1.982, 95% CI: 1.230－2.710, P=0.001). Conclusions:Low HER2 expression in HR Positive patients with breast cancer is more common than in TNBC.There is heterogeneity between the clinicopathological features of patients with zero expression of HER-2 and low expression of HER-2. The survival prognosis of patients with breast cancer with low expression of HER-2 is better than that of patients with zero expression of HER-2, and the expression of HER2 has a significant effect on survival and prognosis.

Objective:To construct a practical education training quality evaluation system that can monitor the entire training process for the master of public health, and to provide a basis for improving the public health education system.Methods:Based on the survey of the current status of the master of public health, combined with the literature survey, the focus group discussion and the expert forum, an evaluation system was established, and the weight coefficient of each index was determined by the analytic hierarchy process (AHP). All data were entered by Excel double-person, and matlabR2018a was used to calculate the weight, and determine the maximum characteristic root of the matrix, consistency index and consistency ratio.Results:The evaluation index system consisted of 7 first-level indicators and 24 second-level indicators. The average authority coefficient of 32 experts was 0.791. The top three items with the highest weight in the first-level indicators were mentor guidance (0.213), professional practice (0.157) and scientific research topics (0.149). The weight coefficient consistency ratio ( CR) was 0.040, showing that the consistency test passed ( CR<0.1). Conclusion:The educational quality evaluation system of the master of public health constructed by the institute is scientific, and the weight of the evaluation index reflects the focus of the postgraduate training process of the master of public health, which can provide a reference for improving the quality of public health professionals.

Allergens ; Asthma ; Humans ; Rhinitis, Allergic ; Seasons ; Skin Tests