CENPN suppresses autophagy and increases paclitaxel resistance in nasopharyngeal carcinoma cells by inhibiting the CREB-VAMP8 signaling axis.

Chemotherapeutic resistance is one of the most common reasons for poor prognosis of patients with nasopharyngeal carcinoma (NPC). We found that CENPN can promote the growth, proliferation and apoptosis resistance of NPC cells, but its relationship with chemotherapeutic resistance in NPC is unclear. Here we verified that the CENPN expression level in NPC patients was positively correlated with the degree of paclitaxel (PTX) resistance and a poor prognosis through analysis of clinical cases. VAMP8 expression was significantly increased after knockdown of CENPN by transcriptome sequencing. We found in cell experiments that CENPN inhibited macroautophagy/autophagy and VAMP8 expression and significantly increased PTX resistance. Overexpression of CENPN reduced the inhibitory effects of PTX on survival, cell proliferation, cell cycle progression and apoptosis resistance in NPC cells by inhibiting autophagy. In turn, knockdown of CENPN can affect the phenotype of NPC cells by increasing autophagy to achieve PTX sensitization. Sequential knockdown of CENPN and VAMP8 reversed the PTX-sensitizing effect of CENPN knockdown alone. Experiments in nude mice confirmed that knockdown of CENPN can increase VAMP8 expression, enhance autophagy and increase the sensitivity of NPC cells to PTX. Mechanistic studies showed that CENPN inhibited the translocation of p-CREB into the nucleus of NPC cells, resulting in the decreased binding of p-CREB to the VAMP8 promoter, thereby inhibiting the transcription of VAMP8. These results demonstrate that CENPN may be a marker for predicting chemotherapeutic efficacy and a potential target for inducing chemosensitization to agents such as PTX.Abbreviations: 3-MA: 3-methyladenine; ATG5: autophagy related 5; CENPN: centromere protein N; CQ: chloroquine; CREB: cAMP responsive element binding protein; ChIP: chromatin immunoprecipitation assay; IC50: half-maximal inhibitory concentration; LAMP2A: lysosomal associated membrane protein 2A; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; NPC: nasopharyngeal carcinoma; NPG: nasopharyngitis; oeCENPN: overexpressed CENPN; PTX: paclitaxel; RAPA: rapamycin; RNA-seq: transcriptome sequencing; shCENPN: small hairpin RNA expression vector targeting the human CENPN gene; shCENPN-shVAMP8: sequential knockdown targeting the human CENPN gene and VAMP8 gene; shVAMP8: small hairpin RNA expression vector targeting the human VAMP8 gene; TEM: transmission electron microscopy; TIR: tumor inhibitory rate; VAMP8: vesicle associated membrane protein 8.

Association of Dietary Polyunsaturated Fatty Acid Intake with Allergic Rhinitis in Adults: A Cross-Sectional Study of NHANES 2005-2006.

INTRODUCTION: The incidence of allergic rhinitis (AR) is increasing year by year, and the pathogenesis is complex, in which diet may play an important role. The role of polyunsaturated fatty acids (PUFAs) in AR is still controversial. Previous studies have looked at the effects of PUFA during pregnancy, childhood, and adolescence. In this study, we aimed to determine the association between dietary intake of PUFA and AR in adults. METHODS: We used the NHANES database from 2005 to 2006 to include a total of 4,211 adult subjects. We collected dietary PUFA intake data and information on AR. Logistic regression and restricted cubic spline models were constructed to examine the association between PUFA intake and AR in adults. The t test was used to compare daily PUFA intakes in patients with and without AR. RESULTS: In the fully adjusted model (OR: 1.016; 95% CI: 1.003; 1.028), PUFA intake was positively correlated with allergic symptoms, hay fever, and AR in adults (p < 0.05). In addition, daily PUFA intake was significantly higher in people with allergic symptoms, hay fever, and AR than in people without the disease (p < 0.01). CONCLUSIONS: Our results suggest a positive association between dietary PUFA intake and AR in adults to a certain extent. Future studies on dietary PUFA dose will provide new strategies for the prevention and treatment of allergic diseases such as AR related to non-pharmaceutical interventions.

Enhancing nasopharyngeal carcinoma cell radiosensitivity by suppressing AKT/mTOR via CENP-N knockdown.

OBJECTIVE: Investigating the impact of centromere protein N (CENP-N) on radiosensitivity of nasopharyngeal carcinoma (NPC) cells. METHODS: Using immunohistochemistry and immunofluorescence to detect CENP-N expression in tissues from 35 patients with radiosensitive or radioresistant NPC. Assessing the effect of combined CENP-N knockdown and radiotherapy on various cellular processes by CCK-8, colony formation, flow cytometry, and Western blotting. Establishing a NPC xenograft model. When the tumor volume reached 100 mm3, a irradiation dose of 6 Gy was given, and the effects of the combined treatment were evaluated in vivo using immunofluorescence and Western blotting techniques. RESULTS: The level of CENP-N was significantly reduced in radiosensitive tissues of NPC (p < 0.05). Knockdown of CENP-N enhanced NPC radiosensitivity, resulting in sensitizing enhancement ratios (SER) of 1.44 (5-8 F) and 1.16 (CNE-2Z). The combined treatment showed significantly higher levels of proliferation suppression, apoptosis, and G2/M phase arrest (p < 0.01) compared to either CENP-N knockdown alone or radiotherapy alone. The combined treatment group showed the highest increase in Bax and γH2AX protein levels, whereas the protein Cyclin D1 exhibited the greatest decrease (p < 0.01). However, the above changes were reversed after treatment with AKT activator SC79. In vivo, the mean volume and weight of tumors in the radiotherapy group were 182 ± 54 mm3 and 0.16 ± 0.03 g. The mean tumor volume and weight in the combined treatment group were 84 ± 42 mm3 and 0.04 ± 0.01 g. CONCLUSION: Knockdown of CENP-N can enhance NPC radiosensitivity by inhibiting AKT/mTOR.

Calpeptin may reverse glucocorticoid-resistance of allergic rhinitis associated with cigarette smoke exposure by down-regulating interferon regulatory factor 1.

Cigarette smoke exposure is an important factor in chronic inflammation in patients with allergic rhinitis (AR); however, the relationship between cigarette smoke and AR-related glucocorticoid resistance requires further study. In mice, calpeptin significantly reduces inflammation of the lower respiratory tract caused by cigarette smoke, but whether it can treat glucocorticoid-resistant AR caused by cigarette smoke requires further research. In this study, we confirmed that cigarette smoke exposure can aggravate the Th2 inflammatory response in AR leading to glucocorticoid resistance. The underlying mechanism may be related to decreased expression of DNA methyltransferase 3a (Dnmt3a), and increased expression of interferon regulatory factor 1 (IRF1). In addition, we found that calpeptin can inhibit the expression of IRF1 and thus treat AR-associated glucocorticoid resistance in rats exposed to cigarette smoke. These data suggest that calpeptin may downregulate IRF1 and therefore treat glucocorticoid resistance in AR-associated with cigarette smoke exposure.

The ratio of total IgE level at week 16 to baseline significantly correlated with the clinical response to omalizumab in moderate to severe allergic rhinitis patients.

OBJECTIVE: To analyze whether the ratio of total IgE level at week 16 to baseline could be used as an indicator to evaluate clinical efficacy of patients treated with omalizumab. METHODS: We retrospectively analyzed the clinical characteristics of 62 patients with moderate-to-severe allergic rhinitis treated with omalizumab, and compared the pre-and post-treatment nasal visual analog scale (n-VAS) scores, the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), Rhinitis Control Assessment Test (RCAT), improvement in nasal congestion, number of acute episodes of rhinitis, and total IgE levels in serum. The relationship between the efficacy of treatment with omalizumab and the change in total IgE levels before and after treatment was further analyzed. RESULTS: This study included 62 patients with moderate-to-severe allergic rhinitis, of which 48 demonstrated significant improvement after 16 weeks of omalizumab therapy; the results of 16 weeks' omalizumab treatment in 14 patients did not show significant improvements in allergic rhinitis symptoms based on RACT scores. After 16 weeks of omalizumab treatment, the RQLQ score decreased from (36.6 ± 13.7) at baseline level to (9.1 ± 12.6) after 16 weeks treatment.The ratio of total IgE at week 16 to total IgE levels at baseline was (2.9 ± 1.4) KU/L in 62 patients. And the ratio of total IgE levels at week 16 to total IgE levels at baseline was (3.3 ± 1.4) KU/L for responders and (1.6 ± 0.5) KU/L for non-responders. CONCLUSION: The ratio of total IgE level at week 16 to baseline significantly correlated with the clinical response to omalizumab in moderate to severe allergic rhinitis patients, when the ratio of total IgE level at week 16 to baseline was ≥2.0. Omalizumab effectively treated patients with moderate-to-severe allergic rhinitis, and improved their quality of life.

LncRNA IUR downregulates miR-144 to regulate PTEN in nasopharyngeal carcinoma.

IUR is a recently identified oncogenic lncRNA in leukaemia, while its roles in nasopharyngeal carcinoma (NPC) are unclear. We aimed to explore the possible involvement of IUR in NPC. IUR and PTEN were downregulated, while miR-144 was upregulated in NPC. In addition, IUR was inversely correlated with miR-144 and positively correlated with PTEN. In NPC cells, overexpression of IUR resulted in a downregulated expression of miR-144 and an upregulated expression of PTEN. Overexpression of miR-144 led to a downregulated expression of PTEN and attenuated the effects of overexpression of IUR. Cell proliferation assay showed that overexpression of IUR and PTEN resulted in decreased NPC cell proliferation rate. Overexpression of miR-144 played an opposite role and attenuated the effects of overexpression of IUR. In conclusion, IUR can downregulate miR-144 to upregulate PTEN in NPC, therefore inhibiting NPC cell proliferation.

Fasting Plasma Glucose and Glycohemoglobin with Allergic Symptoms and Specific Sensitization: Results from NHANES 2005-2006.

OBJECTIVE: The National Health and Nutrition Examination Survey (NHANES) data has been used to study the relationship between fasting plasma glucose (FPG) and glycohemoglobin (A1c) in patients with allergic symptoms and specific sensitization, respectively. METHODS: A total of 1,687 participants and a variety of logistic regression models were selected based on the 2005-2006 NHANES (n = 10,348) for our study to describe the relationship between FPG and A1c in subjects with the sensitivity of allergic symptoms, specific sensitization and specific sensitization of 19 allergens, respectively. On this basis, a variety of logistic regression models were further established for hierarchical analysis to study the limiting conditions when FPG and A1c were related to allergic symptoms. RESULTS: We adjusted the confounding factors and found that the risk of specific sensitization increased with the increase in FPG and A1c. Stratified analysis showed that the risk of allergic symptoms increased with the increase in FPG and A1c when born elsewhere other than in the U.S. and Mexico or underweight or overweight or with hypertension. Furthermore, we found that the risk of egg sensitization increased with the increase in FPG and A1c, while the risk of rat sensitization decreased with the increase in FPG. CONCLUSION: Under certain conditions, FPG and A1c were risk factors for allergic symptoms. FPG and A1c were risk factors for specific sensitization, especially egg sensitization. These findings indicate a possible link between diabetes and allergies.

Giant Cell Tumor and Giant Cell Reparative Granuloma of Bone of the Head: CT and MR Imaging Findings.

BACKGROUND: This study aimed to determine the features and differentiation of Giant Cell Reparative Granuloma (GCRG) and Giant Cell Tumor (GCT) of the head on CT and MRI. METHODS: This retrospective study included six patients with histopathology-confirmed head GCRG and 5 patients with histopathology-confirmed head GCT. All images were independently reviewed by two radiologists. The growth pattern, bone changes, MRI signal intensity, enhancement patterns and other image features were recorded. All patients received CT scans and MR images. RESULTS: All the lesions were located centrally in the bone. Osteolytic bone destruction and expansive growth patterns were observed on CT images. Four of six cases broke the cortical bone with residual cortical bone, and the last two showed a thin cortex in GCRG. Five cases broke the cortical bone with residual cortical bone in GCT. There were enhancing septations in GCT lesions on contrast- enhanced T1-Weighted Images (T1WI) while enhancing septations were not present in GCRG cases. The size of GCT lesions was larger than that of GRCG. GCRG and GCT showed iso-low signals on T1WI and iso-high signals on T2-Weighted Images (T2WI). There was a case with cystic or necrotic lesions in each of the two types of lesions. Osteolytic bone destruction and expansive growth patterns were observed in GCTs and GCRGs. CONCLUSION: The size of the GRCG lesion was smaller than that of the GCT. The presence of enhancing septations and the size of the lesion may distinguish GCTs from GCRG.

Differentiation of eosinophilic and non-eosinophilic chronic rhinosinusitis on preoperative computed tomography using deep learning.

OBJECTIVES: This study aimed to develop deep learning (DL) models for differentiating between eosinophilic chronic rhinosinusitis (ECRS) and non-ECRS (NECRS) on preoperative CT. DESIGN: Axial spiral CT images were pre-processed and used to build the dataset. Two semantic segmentation models based on U-net and Deeplabv3 were trained to segment the sinus area on CT images. All patient images were segmented using the better-performing segmentation model and used for training and testing of the transferred efficientnet_b0, resnet50, inception_resnet_v2, and Xception neural networks. Additionally, we evaluated the performances of the models trained using each image and each patient as a unit. PARTICIPANTS: A total of 878 chronic rhinosinusitis (CRS) patients undergoing nasal endoscopic surgery at Renmin Hospital of Wuhan University (Hubei, China) between October 2016 to June 2021 were included. MAIN OUTCOME MEASURES: The precision of each model was assessed based on the receiver operating characteristic curve. Further, we analyzed the confusion matrix and accuracy of each model. RESULTS: The Dice coefficients of U-net and Deeplabv3 were 0.953 and 0.961, respectively. The average area under the curve and mean accuracy values of the four networks were 0.848 and 0.762 for models trained using a single image as a unit, while the corresponding values for models trained using each patient as a unit were 0.893 and 0.853, respectively. CONCLUSIONS: Combining semantic segmentation with classification networks could effectively distinguish between patients with ECRS and those with NECRS based on preoperative sinus CT images. Furthermore, labeling each patient to build a dataset for classification may be more reliable than labeling each medical image.

Notch2-dependent GATA3+ Treg cells alleviate allergic rhinitis by suppressing the Th2 cell response.

The aim of this study was to investigate the role and mechanism of Notch2-dependent GATA3+ Treg cells in allergic rhinitis (AR). Samples were collected from patients in the control and AR groups to detect differences in the numbers of GATA3+ Treg cells and their intracellular Notch2 levels. The effects of Notch2 on GATA3+ Treg cell differentiation and function in vitro were detected. AR mice were subjected to adoptive transfer of GATA3+ Treg cells to detect changes in the allergic inflammatory response and Th2 cells. Mice with Treg cell-specific knockout of Notch2 were constructed, and an AR model was established to detect the changes. The number of GATA3+ Treg cells and intracellular Notch2 expression in peripheral blood of the AR group were decreased compared with the controls (P < 0.05), and the number of GATA3+ Treg cells was significantly negatively correlated with the level of allergen-specific IgE (sIgE; P < 0.01). In vitro experiments showed that Notch2 promoted the differentiation and immunosuppressive function of GATA3+ Treg cells, and Notch2 directly promoted GATA3 transcription in Treg cells (P < 0.05). Animal experiments indicated that adoptive transfer of GATA3+ Treg cells reduced the allergic inflammatory response in AR mice (P < 0.05). The number of GATA3+ Treg cells was decreased in gene knockout mice (P < 0.05), and autoimmune inflammation was observed. After modeling, the allergic inflammatory response was further aggravated (P < 0.05). Overall, our findings indicate that Notch2 alleviates AR by specifically increasing GATA3+ Treg cell differentiation. Notch2 expressed in Treg cells is expected to be a new therapeutic target for AR.

Allergen immunotherapy enhances the immunosuppressive effects of Treg cells to alleviate allergic rhinitis by decreasing PU-1+ Treg cell numbers.

OBJECTIVE: To investigate the role of Tregs and their subtypes in the treatment of allergic rhinitis with allergen immunotherapy (AIT) as well as the underlying mechanism. METHODS: 1. Thirty-one healthy controls, 29 Allergic rhinitis (AR) patients and 16 AR patients treated with AIT were recruited. The total nasal symptom scores (TNSSs) were calculated. The serum levels of IgE, IL-2, TNF-α, IFN-γ, IL-4, IL-5, IL-6, IL-10 and IL-17 were measured. 2. Changes in the proportions of CD4+ T cells, Treg cells, Treg subtypes and Th1/Th2/Th9/Th17/Tfh cells in the peripheral blood of the subjects in the three groups were measured. 3. The correlations of Treg cells, Treg subtypes and TNSS with the levels of various cytokines in the AR group and AIT group were analysed. RESULTS: 1. Compared with the control group, the TNSS and IgE, IL-5 and IL-6 levels in the AR group were significantly increased, while the IL-2, IFN-γ and IL-10 levels were significantly decreased (P < 0.05). Compared with the AR group, the TNSS and IgE, IL-5 and IL-6 levels in the AIT group were significantly decreased, while the IL-2, IFN-γ and IL-10 levels were significantly increased (P < 0.05). 2. Compared with the control group, the proportions of Tregs, GATA3+ Tregs and Th1 cells in the AR group were significantly reduced, while the proportions of PU-1+ Tregs, T-bet+ Tregs and Th2 cells were significantly increased (P < 0.05). Compared with the AR group, the proportions of Tregs and Th1 cells in the AIT group were significantly increased, while the proportions of PU-1+ Tregs and Th2 cells were decreased (P < 0.05). 3. Correlation analysis showed that Treg cell proportions were negatively correlated with the TNSS, sIgE levels, IL-5 levels and IL-6 levels but positively correlated with the IL-2 and IL-10 levels (P < 0.05). PU-1+ Treg cell proportions were positively correlated with the TNSS, sIgE levels, IL-5 levels and IL-6 levels but negatively correlated with the Treg cell proportions, IL-2 levels and IL-10 levels (P < 0.05). CONCLUSIONS: AIT can reduce the proportions of PU-1+ Treg subtypes in AR patients. PU-1+ Treg cell numbers can potentially be used as an indicator to monitor the therapeutic effect of AIT on AR.

Allergy-related outcomes and sleep-related disorders in adults: a cross-sectional study based on NHANES 2005-2006.

BACKGROUND: Epidemiological evidence between the sleep disorders and allergy-related outcomes is limited. OBJECTIVES: The purpose of the present study was to estimate the relationship between sleep disorders and allergy-related outcomes in adults. METHODS: We built logistic regression models to examine the associations between sleep disorders and allergy-related outcomes in adult participants using the 2005-2006 NHANES database. Allergy-related outcomes included sIgE levels, asthma, hay fever, sneezing, wheezing, and eczema. Sleep disorders included sleep latency, sleep length, sleep problems, OSA symptoms, and daytime sleepiness. A t-test was used for between-group comparisons. RESULTS: Participants with OSA symptoms had 2.72 × higher odds of experiencing hay fever and 1.54 × higher odds of having eczema compared to Non-OSA symptoms participants. Participants with insufficient sleep (≤ 6 h/night) had 1.27 × higher odds of developing allergic sensitisation compared to participants with adequate sleep (7-8 h/night). Sneezing was positively associated with sleep problems (OR: 1.706; 95% CI 1.386, 2.099), OSA symptoms (OR: 1.297; 95% CI 1.049, 1.605), and daytime sleepiness (OR: 1.569; 95% CI 1.205, 2.04). CONCLUSION: Our findings suggest a positive association between allergy-related outcomes and sleep disorders. In particular, OSA symptoms, daytime sleepiness, and sleep problems are strongly associated with allergic conditions.

Anatomical Partition-Based Deep Learning: An Automatic Nasopharyngeal MRI Recognition Scheme.

BACKGROUND: Training deep learning (DL) models to automatically recognize diseases in nasopharyngeal MRI is a challenging task, and optimizing the performance of DL models is difficult. PURPOSE: To develop a method of training anatomical partition-based DL model which integrates knowledge of clinical anatomical regions in otorhinolaryngology to automatically recognize diseases in nasopharyngeal MRI. STUDY TYPE: Single-center retrospective study. POPULATION: A total of 2485 patients with nasopharyngeal diseases (age range 14-82 years, female, 779[31.3%]) and 600 people with normal nasopharynx (age range 18-78 years, female, 281[46.8%]) were included. SEQUENCE: 3.0 T; T2WI fast spin-echo sequence. ASSESSMENT: Full images (512 × 512) of 3085 patients constituted 100% of the dataset, 50% and 25% of which were randomly retained as two new datasets. Two new series of images (seg112 image [112 × 112] and seg224 image [224 × 224]) were automatically generated by a segmentation model. Four pretrained neural networks for nasopharyngeal diseases classification were trained under the nine datasets (full image, seg112 image, and seg224 image, each with 100% dataset, 50% dataset, and 25% dataset). STATISTICAL TESTS: The receiver operating characteristic curve was used to evaluate the performance of the models. Analysis of variance was used to compare the performance of the models built with different datasets. Statistical significance was set at P < 0.05. RESULTS: When the 100% dataset was used for training, the performances of the models trained with the seg112 images (average area under the curve [aAUC] 0.949 ± 0.052), seg224 images (aAUC 0.948 ± 0.053), and full images (aAUC 0.935 ± 0.053) were similar (P = 0.611). When the 25% dataset was used for training, the mean aAUC of the models that were trained with seg112 images (0.823 ± 0.116) and seg224 images (0.765 ± 0.155) was significantly higher than the models that were trained with full images (0.640 ± 0.154). DATA CONCLUSION: The proposed method can potentially improve the performance of the DL model for automatic recognition of diseases in nasopharyngeal MRI. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 1.

Allergen induces CD11c+ dendritic cell autophagy to aggravate allergic rhinitis through promoting immune imbalance.

The level of autophagy in CD11c+ dendritic cell (DC) and its contribution to the subsequent immune imbalance are still unclear. The aim of this study was to investigate the role and mechanism of them in promoting the allergic inflammatory response. Nasal mucosa tissues were collected from allergic rhinitis (AR) mice and their control group to detect the expression of LC3II, P62 and ATG5 and CD11c+DC autophagy. Different concentration of OVA or the combination of OVA and autophagy inhibitor (3-MA) were used to induce the differentiation of mouse bone marrow-derived DCs (CD11c+BMDCs). Differences in LC3II, P62 and ATG5 expression and autophagosome formation were detected. BMDCs in the above groups were cocultured with spleen lymphocytes to detect the proportions of effector T cells and changes in cytokines. OVA-loaded BMDCs were injected intravenously into C57BL/6 mice to develop allergic model. The nasal mucosa of mice in the AR group showed significantly increased LC3II and ATG5 protein expression, whereas showed significantly decreased P62 protein expression. Moreover, LC3II was mainly co-expressed with CD11c+ DC markers. In vitro, OVA stimulation induced the increase of autophagosomes and the expression of autophagy-related proteins in BMDCs in a dose-dependent manner, and inhibition of autophagy showed significantly decreased LC3II and ATG5 expression and autophagosome abundance. In addition, OVA-induced BMDC autophagy can affect CD4+T cell differentiation and related cytokine levels, however, the Th1/Th2/Th9/Th17/Treg/Tfh cell immune imbalances were significantly reversed after the addition of 3-MA. Adoptive transfer of OVA-loaded BMDCs could promote the allergic inflammation, while the administration of 3-MA on OVA-loaded BMDCs could significantly reduce the AR inflammation. Overall, our findings demonstrate that allergen can induce CD11c+DC autophagy in a dose-dependent manner and promote the immune imbalance of downstream T cells towards a proinflammatory phenotype.

A Multicenter Study of Prevalence and Risk Factors for Allergic Rhinitis in Primary School Children in 5 Cities of Hubei Province, China.

BACKGROUND: Few data are available concerning the prevalence and risk factors for allergic rhinitis (AR) in school children in Hubei Province which is located in the central part of China. This study investigated the epidemiological features of AR among school children in Hubei Province. METHODS: A cross-sectional questionnaire survey on AR in school children was carried out in 5 cities in Hubei Province by cluster sampling from June to September 2018. Questionnaires were filled out by children and their parents jointly. The diagnostic criteria of AR were according to the SFAR. Questions from the questionnaire were used to examine the pattern of AR. Logistic regression analysis was used to assess the risk factors for childhood allergies. RESULTS: The total prevalence rate of AR was 16.16%, with 24.31% (Wuhan), 4.34% (Xiangyang), 4.31% (Tianmen), 10.92% (Jingmen), and 11.42% (Huangshi), respectively. The prevalence of AR was positively correlated with gross domestic product per capita (p < 0.05). Multivariate analysis revealed that male, city of Wuhan, family history of allergy, food allergy, drug allergy, air purifier, exposure to dust, living in towns or urban area before 2 years old, maternal age for 26-35 years old, and frequent application of antibiotics increased the risk of AR, while daily outdoor time for 1-2 h, daily sleeping time >8 h, siblings, and breastfeeding for >6 months reduced the risk significantly. CONCLUSION: We found the apparent geographic variation of children allergies in Hubei Province. Both genetic and environment factors had impacts on the prevalence of AR in school children. Public policies should specifically target at the local risk factors for different areas.

The IRF2/CENP-N/AKT signaling axis promotes proliferation, cell cycling and apoptosis resistance in nasopharyngeal carcinoma cells by increasing aerobic glycolysis.

BACKGROUND: Centromere protein N (CENP-N) has been reported to be highly expressed in malignancies, but its role and mechanism in nasopharyngeal carcinoma (NPC) are unknown. METHODS: Abnormal CENP-N expression from NPC microarrays of GEO database was analyzed. CENP-N expression level was confirmed in NPC tissues and cell lines. Stable CENP-N knockdown and overexpression NPC cell lines were established, and transcriptome sequencing after CENP-N knockdown was performed. In vitro and in vivo experiments were performed to test the impact of CENP-N knockdown in NPC cells. ChIP and dual luciferase reporter assays were used to verify the combination of IRF2 and CENP-N. Western blot analysis, cellular immunofluorescence, immunoprecipitation and GST pulldown assays were used to verify the combination of CENP-N and AKT. RESULTS: CENP-N was confirmed to be aberrantly highly expressed in NPC tissues and cell lines and to be associated with high 18F-FDG uptake in cancer nests and poor patient prognosis. Transcriptome sequencing after CENP-N knockdown revealed that genes with altered expression were enriched in pathways related to glucose metabolism, cell cycle regulation. CENP-N knockdown inhibited glucose metabolism, cell proliferation, cell cycling and promoted apoptosis. IRF2 is a transcription factor for CENP-N and directly promotes CENP-N expression in NPC cells. CENP-N affects the glucose metabolism, proliferation, cell cycling and apoptosis of NPC cells in vitro and in vivo through the AKT pathway. CENP-N formed a complex with AKT in NPC cells. Both an AKT inhibitor (MK-2206) and a LDHA inhibitor (GSK2837808A) blocked the effect of CENP-N overexpression on NPC cells by promoting aerobic glycolysis, proliferation, cell cycling and apoptosis resistance. CONCLUSIONS: The IRF2/CENP-N/AKT axis promotes malignant biological behaviors in NPC cells by increasing aerobic glycolysis, and the IRF2/CENP-N/AKT signaling axis is expected to be a new target for NPC therapy.

[The research progress of mechanism of allergen immunotherapy in allergic rhinitis].

Allergic rhinitis（AR） is a chronic non-infectious nasal mucosal disease mediated by IgE. It can be divided into seasonal and perennial according to the types of allergens.At present, there are many treatments for AR, among which allergen immunotherapy（AIT） is the only treatment option that can change the natural process of AR.AIT can improve innate immune response by reducing local hypertrophy, eosinophils, basophils and type 2 innate lymphocytes, and affect various T cells, B cells and many cytokines to regulate adaptive immunity. The mechanism of AIT on immune response is complex.In this review, the mechanism of immunotherapy on the innate and adaptive immunity of AR patients is highlighted, hoping to further understand the immunotherapy pathway of AR, and provide more theoretical basis for immunotherapy of AR.

Erratum: Neonatal Immune State Is Influenced by Maternal Allergic Rhinitis and Associated With Regulatory T cells.

This corrects the article on p. 133 in vol. 9, PMID: 28102058.

Sevoflurane promotes the apoptosis of laryngeal squamous cell carcinoma in-vitro and inhibits its malignant progression via miR-26a/FOXO1 axis.

Laryngeal squamous cell carcinoma (LSCC) is a laryngeal malignancy with a high mortality rates, and its treatment remains difficult. Sevoflurane is a surgical anesthesia which has anti-tumor effect. This investigation assessed the effects of LSCC cells treatment with Sevoflurane in vitro and in vivo. Hep-2 and Tu177 cells, human LSCC samples and BALB/C nude mice were used for result assessments. Cell viability, proliferation, migration and invasion were assessed via Cell Count Kit-8, wound healing assay and transwell invasion assay respectively. MiR-26a and FOXO1 expressions was examined by qRT-PCR. FOXO1, E-cadherin, N-cadherin and vimentin activities were examined by Western blotting. Moreover, animal experiments were performed to verify our findings in vitro. Lastly, miR-26a and FOXO1 expression levels in clinical samples were analyzed. According to the results, Sevoflurane decreased LSCC cells' viability and even stimulated their apoptosis in vitro and in vivo. Moreover, it could reduce the migration, invasion and EMT. Mechanistically, sevoflurane could downregulate miR-26a expression and that miR-26a could negatively modulate FOXO1 activity. Thus, sevoflurane could increase FOXO1 activity. In the clinical samples, miR-26a expression was significantly upregulated, but FOXO1 was remarkably down-regulated and miR-26a expression in LSCC was linked with better prognosis. In conclusion, MiR-26a is increased and FOXO1 is reduced in human LSCC, Sevoflurane inhibits proliferation and mediates apoptosis of LSCC cells. Further, MiR-26a binds FOXO1 directly, and FOXO1 expression is down-regulated by Sevoflurane. Finally, Sevoflurane triggers LSCC cells apoptosis in vivo. Sevoflurane use to target miR-26a/FOXO1 may be a novel alternative for LSCC therapy.

PLAC8 gene knockout increases the radio-sensitivity of xenograft tumors in nude mice with nasopharyngeal carcinoma by promoting apoptosis.

In vitro cell experiments showed that knocking out the placenta-specific protein 8 (PLAC8) gene significantly increased the sensitivity of tumor cells to radiation. This study used two nude mouse models of nasopharyngeal carcinoma (NPC) to investigate the radio-sensitization and molecular mechanism of PLAC8 knockout in vivo. The expression of PLAC8 in 120 NPC tissues and 30 nasopharyngitis (NPG) tissues was detected by immunohistochemistry (IHC) to analyze the relationship between PLAC8 and neck lymph node metastasis and prognosis in NPC patients. The mRNA expression level of PLAC8 in several NPC cell lines was detected by semi-quantitative RT-PCR. The PLAC8 gene was knocked out in CNE-2 cells using CRISPR/Cas9. The effect of PLAC8 gene knockout on the radiotherapy sensitivity of NPC cells was analyzed by establishing model 1 and model 2 tumor-bearing nude mouse models with two different irradiation methods. The expression of γH2AX, Bax, Bcl-2, Caspase-3 and cleaved Caspase-3 was detected by immunofluorescence (IF), IHC and western blot analysis. PLAC8 expression was significantly increased in NPC tissue samples and NPC cell lines compared with NPG tissue samples and normal cell lines (P<0.01). PLAC8 upregulation was associated with lymph node metastasis and a poor prognosis in patients with NPC (P<0.01). Both animal models showed that radiotherapy after PLAC8 knockout significantly slowed tumor growth and reduced tumor volume, with tumor inhibition rates of 100% and 66.04%, respectively. In model 2, PLAC8 knockout with radiotherapy increased the expressions of γH2AX, Bax, Caspase-3 and cleaved Caspase-3 but decreased the expression of Bcl-2 (P<0.01). In model 1, there was no tumor formation at the site where the cancer cells were injected. The expression levels of γH2AX, Bax, Caspase-3 and cleaved Caspase-3 in skin tissues taken at the injection site were lower than those in NPC tissues treated with radiotherapy, while the expression level of Bcl-2 was higher (P<0.01). PLAC8 expression is closely related to neck metastasis and the prognosis of NPC. PLAC8 gene knockout significantly increases the radio-sensitivity of NPC cells in vivo by promoting apoptosis, which is an effective strategy for the radiotherapy sensitization of NPC.