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.

Copper-Catalyzed Asymmetric Allylation of N-Aryl Aldimines.

The copper-catalyzed enantioselective allylation reaction of N-aryl aldimines has been developed using a combination of Cu(OAc)2 and SPINOL-based phosphonamidite. This protocol significantly broadens the substrate scope, such that imines bearing various ortho-substituents on the N-aryl were converted smoothly into homoallylic amines in up to 99% yield and 98% ee. Taking advantage of the diversity of the N-aryl motif, three kinds of N-heterocyclic compounds were constructed, respectively, from the corresponding homoallylic amines in merely one step.

Association between 19 Allergens and Chronic Constipation in Adults: NHANES 2005-2006.

INTRODUCTION: There are increasing reports of a link between chronic constipation and allergies in children. However, similar epidemiological evidence is limited in the general adult population. Therefore, in this study, we attempted to assess the association between chronic constipation and allergy in adults aged ≥20 years in the USA. METHODS: We established a logistic regression model to test the relationship between chronic constipation and 19 specific immunoglobulin E (sIgE) types in adults aged ≥20 years using large-sample data from the National Health and Nutrition Examination Survey database (2005-2006). The weekly defecation times of the allergic and non-allergic groups were compared using the t test. RESULTS: We found that sIgE-sensitized participants had a 0.723 lower risk of chronic constipation than the general population (95% confidence interval (CI) = 0.566-0.923). There was a negative association between chronic constipation and sensitizations to peanut (odds ratio (OR) = 0.579, 95% CI = 0.381-0.935), egg (OR = 0.335, 95% CI = 0.134-0.838), dog (OR = 0.723, 95% CI = 0.522-0.965), and cockroach (OR = 0.540, 95% CI = 0.373-0.784). In addition, the frequency of defecation per week increased significantly in people allergic to peanuts and cockroaches (p < 0.05). DISCUSSION/CONCLUSION: The results of this study demonstrate an inverse relationship between sIgE sensitization and chronic constipation in adults. However, the specific association mechanism needs to be further studied.

The efficacy of steroid-eluting stents on the local inflammation of chronic rhinosinusitis with nasal polyposis after endoscopic sinus surgery: a multicenter prospective longitudinal study.

PURPOSE: Attenuating local inflammation of chronic rhinosinusitis with nasal polyps (CRSwNP) after endoscopic sinus surgery (ESS) was crucial. Corticosteroids were generally exploited to ameliorate the postoperative state of CRSwNP. This study aims to verify the efficacy of steroid-eluting stents on the local inflammation of CRSwNP following ESS. METHODS: 57 CRSwNP were enrolled from September 2021 to April 2022. 30 were with stents, and 27 were without stents after ESS. Eosinophilic cationic protein (ECP), myeloperoxidase (MPO), eosinophil, and neutrophil levels in nasal secretions, as well as visual analog scale (VAS) and modified perioperative sinus endoscopy (POSE) scores, were assessed preoperatively and after 2, 4, 8, and 12 weeks. RESULTS: All subjects of CRSwNP exhibited reduced results of eosinophil levels, neutrophil levels, nasal obstruction, nasal discharge, loss of smell, and total VAS scores after 12 weeks compared to the preoperative ones (p < 0.05). Compared with control subjects, CRSwNP with stents acquired lower levels of ECP, MPO, loss of smell, total VAS, and POSE scores at four follow-up visits, as well as reduced eosinophil and neutrophil levels in nasal secretions after 12 weeks (p < 0.05). Correlation analysis revealed that postoperative ECP and MPO levels of CRSwNP in nasal secretions correlated strongly with eosinophil and neutrophil levels, respectively, as well as POSE scores (r > 0.6). CONCLUSION: These findings indicated that steroid-eluting stents might be an acclaimed option for CRSwNP in alleviating local inflammation to acquire a superior state after ESS.

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.

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.

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.

Upregulation of claudin­4 by Chinese traditional medicine Shenfu attenuates lung tissue damage by acute lung injury aggravated by acute gastrointestinal injury.

CONTEXT: Many studies have explored new methods to cure acute lung injury (ALI); however, none of those methods could significantly change the high mortality rate of ALI. Shenfu is a Chinese traditional medicine that might be effective against ALI. OBJECTIVE: Our study explores the therapeutic potential of Shenfu in ALI. MATERIALS AND METHODS: Male C57BL/6 mice were assigned to control, lipopolysaccharide (LPS) (500 µg/100 µL per mouse), and LPS + Shenfu (30 mL/kg) groups. Shenfu (10 µL/mL) was added to LPS (10 µg/mL) treated MLE-12 cells for 48 h in vitro. Male C57BL/6 mice were divided into four groups: LPS, LPS + 3% dextran sulphate sodium (DSS), 3% DSS + Shenfu, and LPS + 3% DSS + Shenfu. RESULTS: Compared with the ALI group, Shenfu reduced wet/dry weight ratio (19.8%, 36.2%), and reduced the IL-2 (40.9%, 61.6%), IFN-γ (43.5%, 53.3%) TNF-α (54.1%, 42.1%), IL-6 (54.8%,70%), and IL-1ß (39.9%, 65.1%), reduced serum uric acid (18.8%, 48.7%) and creatinine (17.4%, 41.1%). Moreover, Shenfu enhanced cell viability (17.2%, 59.9%) and inhibited cell apoptosis (63.0%) and p38/ERK phosphorylation in in vitro cultured epithelial cells with LPS stimulation. Mechanistically, Shenfu mediated the protective effect by upregulating claudin-4 expression. In addition, Shenfu could protect against both lung and intestinal epithelial damage in acute gastrointestinal injury-exacerbated ALI. DISCUSSION AND CONCLUSIONS: Taken together, the results revealed the therapeutic effect and the underlying mechanism of Shenfu injection in an ALI in mouse model, indicating its clinical potential to treat patients with ALI.

The value of complete blood count for the prognosis analysis of preoperative esophageal squamous cell carcinoma.

OBJECTIVE: To investigate the predictive value of preoperative complete blood count for the survival of patients with esophageal squamous cell carcinoma. METHODS: A total of 1587 patients with pathologically confirmed esophageal squamous cell carcinoma who underwent esophagectomy in the Cancer Hospital Affiliated to Xinjiang Medical University from January 2010 to December 2019 were collected by retrospective study. A total of 359 patients were as the validation cohort from January 2015 to December 2016, and the remaining 1228 patients were as the training cohort. The relevant clinical data were collected by the medical record system, and the patients were followed up by the hospital medical record follow-up system. The follow-up outcome was patient death. The survival time of all patients was obtained. The Cox proportional hazards regression model and nomogram were established to predict the survival prognosis of esophageal squamous cell carcinoma by the index, their cut-off values obtained the training cohort by the ROC curve. The Kaplan-Meier survival curve was established to express the overall survival rate. The 3-year and 5-year calibration curves and C-index were used to determine the accuracy and discrimination of the prognostic model. The decision curve analysis was used to predict the potential of clinical application. Finally, the validation cohort was used to verify the results of the training cohort. RESULTS: The cut-off values of NLR, NMR, LMR, RDW and PDW in complete blood count of the training cohort were 3.29, 12.77, 2.95, 15.05 and 13.65%, respectively. All indicators were divided into high and low groups according to cut-off values. Univariate Cox regression analysis model showed that age (≥ 60), NLR (≥3.29), LMR (< 2.95), RDW (≥15.05%) and PDW (≥13.65%) were risk factors for the prognosis of esophageal squamous cell carcinoma; multivariate Cox regression analysis model showed that age (≥ 60), NLR (≥3.29) and LMR (< 2.95) were independent risk factors for esophageal squamous cell carcinoma. Kaplan-Meier curve indicated that age <  60, NLR < 3.52 and LMR ≥ 2.95 groups had higher overall survival (p <  0.05). The 3-year calibration curve indicated that its predictive probability overestimate the actual probability. 5-year calibration curve indicated that its predictive probability was consistent with the actual probability. 5 c-index was 0.730 and 0.737, respectively, indicating that the prognostic model had high accuracy and discrimination. The decision curve analysis indicated good potential for clinical application. The validation cohort also proved the validity of the prognostic model. CONCLUSION: NLR and LMR results in complete blood count results can be used to predict the survival prognosis of patients with preoperative esophageal squamous cell carcinoma.

Adverse reactions to subcutaneous immunotherapy in patients with allergic rhinitis, a real-world study.

PURPOSE: The efficacy of subcutaneous immunotherapy (SCIT) for allergic rhinitis (AR) have been proven but application is still limited by concerns about the safety. The aims of this study were to investigate the incidence of adverse reactions and to ascertain possible risk factors in patients treated with SCIT in central China. METHODS: This study retrospectively analyzed the application of SCIT from 2016 to 2018, in 236 patients with AR. After each injection, allergen dosage and details about local reactions (LRs)/systemic reactions (SRs) were recorded. RESULTS: Totaling 236 patients received 5844 injections. The rates of LR were 3.0% per injection and 34.7% per patient, while the rates of SR were 0.48% per injection and 10.6% per patient. 86.9 percent LRs were small. Most SRs were grade 1 (16/57.1%), followed by grade 2 (8/28.6%), grade 3 (4/14.3%). No fatal SRs was recorded. Children, high sensitization and absence of premedication were identified as risk factors for LRs. Recurrent LRs increased the risk of SRs. Premedication could reduce the number and severity of LRs, but not SRs. Dual therapy with antihistamine and montelukast did not provide additional benefit when compared with antihistamine alone. CONCLUSION: The incidence of SRs was low while LRs were common in SCIT. Children may be prone to develop LRs, while pretreatments could reduce the number and severity of LRs. Recurrent LRs was a risk factor for SRs.

Increased Expressions and Roles of CC Chemokine Ligand 21 and CC Chemokine Ligand 25 in Chronic Rhinosinusitis with Nasal Polyps.

INTRODUCTION: Chronic rhinosinusitis (CRS) is a local inflammation of the nasal mucosa and sinus that persists for >12 weeks. As CC chemokine ligand (CCL) 19 expression is known to be elevated in CRS, and CCL 19, CCL21, and CCL25 share the same atypical chemokine receptor 4, so we focused on CCL21 and CCL25. OBJECTIVES: To investigate the expression of CCL21 and CCL25 in different types of CRS and their significance in CRS development. METHODS: A total of 116 patients participated in the study, and uncinate process mucosa or nasal polyp (NP) specimens were collected during surgery. Western blotting and immunohistochemistry were performed to detect the expression of CCL21 and CCL25, respectively, in the nasal mucosa. Immunofluorescence was used to determine their cellular localization in NPs, whereas macrophage culture was used to determine their relationships with macrophages. RESULTS: Immunohistochemistry revealed that the expressions of CCL21 and CCL25 were increased in NPs only. Western blotting revealed that these expressions were gradually increased in control, CRS without NP and CRS with NP groups and were positively correlated with disease severity. Furthermore, increased expressions of CCL21 and CCL25 in NPs were not related to eosinophil infiltration. Immunofluorescence results demonstrated colocalization of CCL25+ cells and CD68+ macrophages. CCL25 expression was increased in macrophage culture, especially in M1 macrophages, while CCL21 expression was not significantly associated with macrophages. CONCLUSIONS: CCL21 and CCL25 were significantly upregulated in NPs and positively correlated with disease severity. CCL25 upregulation was related to M1 macrophages.

A quantum dot-based lateral flow immunoassay for the rapid, quantitative, and sensitive detection of specific IgE for mite allergens in sera from patients with allergic rhinitis.

The prevalence of allergic rhinitis (AR) is increasing worldwide. However, the current systems used to measure levels of immunoglobulin E (IgE) in sera are associated with several disadvantages that limit their further application. Consequently, there is a need to develop novel highly sensitive strategies that can rapidly detect IgE in a quantitative manner. The development of such systems will significantly enhance our ability to diagnose, treat, and even prevent AR. Herein, we describe our experience of using quantum dot-based lateral flow immunoassay (QD-LFIA), combined with a portable fluorescence immunoassay chip detector (PFICD), to detect serum-specific IgE against Dermatophagoides pteronyssinus (Der-p) and Dermatophagoides farinae (Der-f), two common mite allergens in China. Our data showed that our system could detect serum-specific levels of IgE against Der-p and Der-f as low as 0.093 IU/mL and 0.087 IU/mL, respectively. We also established a standard curve to determine serum-specific IgE concentrations that correlated well with the clinical BioIC microfluidics system. The sensitivity of our assay was 96.7% for Der-p and 95.5% for Der-f, while the specificity was 87.2% for Der-p and 85.3% for Der-f. Collectively, our results demonstrate that QD-LFIA is a reliable system that could be applied to detect serum-specific IgE in accordance with clinical demands. This QD-LFIA strategy can be applied at home, in hospitals, and in pharmacies, with reduced costs and time requirements when compared with existing techniques. In the future, this system could be developed to detect other types of allergens and in different types of samples (for example, whole blood). Graphical abstract We describe our experiment using a quantum dot-based lateral flow immunoassay combined with a portable fluorescence immunoassay chip detector for both qualitative and quantitative detection of serum-specific IgE against two common mite allergens. This strategy can be applied at home, in hospitals, and in pharmacies, with reduced costs and time requirements. In the future, this system could be developed to detect other types of allergens and in different types of samples.

Predicting domain-specific actions in expert table tennis players activates the semantic brain network.

Motor expertise acquired during long-term training in sports enables top athletes to predict the outcomes of domain-specific actions better than nonexperts do. However, whether expert players encode actions, in addition to the concrete sensorimotor level, also at a more abstract, conceptual level, remains unclear. The present study manipulated the congruence between body kinematics and the subsequent ball trajectory in videos of an expert player performing table tennis serves. By using functional magnetic resonance imaging, the brain activity was evaluated in expert and nonexpert table tennis players during their predictions on the fate of the ball trajectory in congruent versus incongruent videos. Compared with novices, expert players showed greater activation in the sensorimotor areas (right precentral and postcentral gyri) in the comparison between incongruent vs. congruent videos. They also showed greater activation in areas related to semantic processing: the posterior inferior parietal lobe (angular gyrus), middle temporal gyrus, and ventromedial prefrontal cortex. These findings indicate that action anticipation in expert table tennis players engages both semantic and sensorimotor regions and suggests that skilled action observation in sports utilizes predictions both at motor-kinematic and conceptual levels.

Different effects of allergic rhinitis on nasal mucosa remodeling in chronic rhinosinusitis with and without nasal polyps.

BACKGROUND: Allergic rhinitis (AR) has been reported to be associated with chronic rhinosinusitis (CRS). The objective of this study was to investigate the effect of AR on nasal mucosa remodeling in CRS. METHODS: Patients were enrolled and divided into the following groups: CRS with nasal polyps (NP) with allergic rhinitis (AR)(CRSwNPwAR; n = 20), CRS with NP without AR (CRSwNPsAR; n = 20), CRS without NP with AR (CRSsNPwAR; n = 20), CRS without NP without AR (CRSsNPsAR; n = 20), AR without CRS (AR; n = 20) and controls (n = 14). Eosinophil infiltration, mucus production, and collagen deposition were examined by hematoxylin and eosin, periodic acid schiff and masson's trichrome staining, respectively. VEGF-A and microvessel density were detected by immunohistochemistry. The expression of remodeling markers, including TGF-ß1, MMP-7, MMP-9 and TIMP-1 were measured by Western blot. RESULTS: The expression of remodeling factors, including VEGF-A, CD31, CD34 and TIMP-1 were significantly increased in CRSwAR compared to CRSsAR. Goblet cell hyperplasia, as well as VEGF-A, CD31, CD34, and MMP-9 expression were significantly higher in CRSwNPwAR compared to CRSwNPsAR. However, the expression of collagen fibers, MMP-7 and TGF-ß1 were significantly higher in CRSsNPwAR compared to CRSsNPsAR. CONCLUSIONS: AR could enhance the remodeling process in CRS. Moreover, AR had different effects on CRSwNP and CRSsNP.

Neural correlates of interference resolution in the multi-source interference task: a meta-analysis of functional neuroimaging studies.

BACKGROUND: Interference resolution refers to cognitive control processes enabling one to focus on task-related information while filtering out unrelated information. But the exact neural areas, which underlie a specific cognitive task on interference resolution, are still equivocal. The multi-source interference task (MSIT), as a particular cognitive task, is a well-established experimental paradigm used to evaluate interference resolution. Studies combining the MSIT with functional magnetic resonance imaging (fMRI) have shown that the MSIT evokes the dorsal anterior cingulate cortex (dACC) and cingulate-frontal-parietal cognitive-attentional networks. However, these brain areas have not been evaluated quantitatively and these findings have not been replicated. METHODS: In the current study, we firstly report a voxel-based meta-analysis of functional brain activation associated with the MSIT so as to identify the localization of interference resolution in such a specific cognitive task. Articles on MSIT-related fMRI published between 2003 and July 2017 were eligible. The electronic databases searched included PubMed, Web of Knowledge, and Google Scholar. Differential BOLD activation patterns between the incongruent and congruent condition were meta-analyzed in anisotropic effect-size signed differential mapping software. RESULTS: Robustness meta-analysis indicated that two significant activation clusters were shown to have reliable functional activity in comparisons between incongruent and congruent conditions. The first reliable activation cluster, which included the dACC, medial prefrontal cortex, supplementary motor area, replicated the previous MSIT-related fMRI study results. Furthermore, we found another reliable activation cluster comprising areas of the right insula, right inferior frontal gyrus, and right lenticular nucleus-putamen, which were not typically discussed in previous MSIT-related fMRI studies. CONCLUSIONS: The current meta-analysis study presents the reliable brain activation patterns on MSIT. These findings suggest that the cingulate-frontal-striatum network and right insula may allow control demands to resolve interference on MSIT. These results provide new insights into the neural mechanisms underlying interference resolution.

MicroRNA-146a induction during influenza H3N2 virus infection targets and regulates TRAF6 levels in human nasal epithelial cells (hNECs).

We have previously shown that human nasal epithelial cells (hNECs) are highly permissive cells for respiratory viruses including influenza A virus (IAV) and respiratory syncytial virus. Recent studies have indicated that microRNAs (miRNAs) are involved in virus-host relationship, and this led us to investigate its essential roles in the in vitro hNECs model derived from multiple donors. By comparing the differential expression of miRNAs upon IAV infection among animal and cell line studies, candidates were selected with focus on the initial immune response. After infection of influenza H3N2 virus, hNECs showed constant increase virus titer at 24-72h post-infection (hpi); accompanied with a significantly elevated level of miR-146a-5p at 72 hpi. The exponential elevation of progeny virus titer correlated with a key influenza sensing Toll-like receptor (TLR)7 pathway. TLR7 downstream gene transcripts, myeloid differentiation primary response gene 88 (MyD88), interferon regulator factor 7 (IRF7), and interferon-ß (IFN-ß) were significantly upregulated at 48 and 72 hpi, while interleukin-1 receptor-associated kinase 1 (IRAK1) and TNF receptor associated factor-6 (TRAF6) were unchanged. Interestingly, when miR-146a was overexpressed with miRNA mimics prior to H3N2 infection, further decreased transcripts of TRAF6, but not IRAK1, were detected. By using the in vitro hNEC model, we demonstrated that H3N2-induced miR-146a specifically targets and regulates TRAF6 expression; but not IRAK expression in the nasal epithelium. We also found that unlike the cell model studies that lead to our studies, when ran across a heterogeneous model of different individual, miRNA signals were highly varied and the expression of most miRNAs, including miR-146a-5p, was more subdued compared to homogenous cell line model, highlighting a need for a more thorough analysis of miRNA signals and targets in a model more mimicking a clinical influenza infection.

Comparison of outcomes between endoscopic surgery and conventional nasal packing for epistaxis in the posterior fornix of the inferior nasal meatus.

OBJECTIVE: To investigate the clinical features of epistaxis in the posterior fornix of the inferior nasal meatus and compare the treatment outcomes of endoscopic surgery and conventional nasal packing for this intractable form of epistaxis. METHODS: Between August 2011 and August 2014, the medical records of 53 adult patients with idiopathic epistaxis in the posterior fornix of the inferior nasal meatus diagnosed by nasal endoscopy were obtained from our department. Of these, 38 patients underwent endoscopic surgery (surgery group) and 15 received a nasal pack (packing group). The patients' background characteristics, incidence of re-bleeding, extent of discomfort after treatment as assessed using a 10-point visual analogue scale (VAS) and incidence of nasal cavity adhesion after treatment were analysed. RESULTS: There were no significant differences in background characteristics between the two groups. The incidence of re-bleeding (0/38 vs. 4/15, surgery vs. control, P = 0.001), VAS score for discomfort (2.4 ± 1.4 vs. 7.6 ± 1.0, surgery vs. control, P = 0.001) and incidence of nasal cavity adhesion after treatment (2/38 vs. 7/15, surgery vs. control, P = 0.007) were significantly lower in the surgery group than in the packing group. CONCLUSION: Endoscopic surgery is superior to conventional nasal packing for the management of epistaxis in the posterior fornix of the inferior nasal meatus. During surgery, it is crucial to expose the bleeding sites by shifting the inferior turbinate inward by fracture.

Exogenous interleukin-10 alleviates allergic inflammation but inhibits local interleukin-10 expression in a mouse allergic rhinitis model.

BACKGROUND: Interleukin-10 (IL-10) has an important anti-inflammatory and immunoregulatory function, and its expression is negatively correlated with the development and severity of allergic rhinitis (AR). However, the in vivo effects of exogenous IL-10 on AR have not been studied and the mechanisms underlying the effects of IL-10 have not been fully understood. Here, we investigated the effects of intranasal administration of recombinant mouse (rm) IL-10 on the expression of Th responses and local IL-10 in a mouse model of AR induced by ovalbumin. RESULTS: Administration of rmIL-10 during challenge significantly reduced the number of eosinophils and mast cells, as well as Type 2 helper T (Th2) and Th17 cell related cytokine and transcription factor levels in the nasal mucosa and nasal lavage fluid in AR mice. The rmIL-10 treatment significantly inhibited the number of IL-10-positive cells and IL-10 mRNA expression in the nasal mucosa in AR mice. CONCLUSION: Our results show that exogenous IL-10 administrated in challenge phase alleviates nasal allergic inflammation in AR mice, most likely by inhibiting Th2 and Th17 responses. It can also inhibit local IL-10 levels in the nasal mucosa. Our findings indicate that IL-10 may have the potential as an inhibitor of AR.

Fecal Microbiota Transplantation Alleviates Allergic Rhinitis via CD4+ T Cell Modulation Through Gut Microbiota Restoration.

Allergic rhinitis (AR) is an allergic condition of the upper respiratory tract with a complex pathogenesis, including epithelial barrier disruption, immune regulation, and gut microbiota, which is not yet fully understood. Gut microbiota is closely linked to allergic diseases, including AR. Fecal microbiota transplantation (FMT) has recently been recognized as a potentially effective therapy for allergic diseases. However, the efficacy and mechanism of action of FMT in AR remain unknown. Herein, we aimed to observe the implications of gut microbiota on epithelial barrier function and T cell homeostasis, as well as the effect of FMT in AR, using the ovalbumin (OVA)-induced AR mice. The intestinal microbiota of recipient mice was cleared using an antibiotic cocktail; thereafter, FMT was performed. Subsequently, the nasal symptom scores and histopathological features of colon and nasal mucosa tissues of mice were monitored, and serum OVA-sIgE and cytokines of IL-4, IFNγ, IL-17A, and IL-10 cytokine concentrations were examined. Thereafter, tight junction protein and CD4+ T cell-related transcription factor and cytokine expressions were observed in the colon and nasal mucosa, and changes in the expression of PI3K/AKT/mTOR and NFκB signaling pathway were detected by WB assay in each group. Fecal DNA was extracted from the four mice groups for high-throughput 16S rRNA sequencing. FMT ameliorated nasal symptoms and reduced nasal mucosal inflammation in AR mice. Moreover, according to 16S rRNA sequencing, FMT restored the disordered gut microbiota in AR mice. Following FMT, ZO-1 and claudin-1 and Th1/Th2/Th17-related transcription factor and cytokine expressions were upregulated, whereas Treg cell-related Foxp3 and IL-10 expressions were downregulated. Mechanistic studies have revealed that FMT also inhibited PI3K/AKT/mTOR and NF-κB pathway protein phosphorylation in AR mouse tissues. FMT alleviates allergic inflammation in AR by repairing the epithelial barrier and modulating CD4+ T cell balance and exerts anti-inflammatory effects through the PI3K/AKT/mTOR and NF-κB signaling pathways. Moreover, gut microbiota disorders are involved in AR pathogenesis. Disturbed gut microbiota causes an altered immune-inflammatory state in mice and increases susceptibility to AR. This study suggested the regulatory role of the gut-nose axis in the pathogenesis of AR is an emerging field, which provides novel directions and ideas for the treatment of AR.

Computational identification and experimental verification of a novel signature based on SARS-CoV-2-related genes for predicting prognosis, immune microenvironment and therapeutic strategies in lung adenocarcinoma patients.

Background: Early research indicates that cancer patients are more vulnerable to adverse outcomes and mortality when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Nonetheless, the specific attributes of SARS-CoV-2 in lung Adenocarcinoma (LUAD) have not been extensively and methodically examined. Methods: We acquired 322 SARS-CoV-2 infection-related genes (CRGs) from the Human Protein Atlas database. Using an integrative machine learning approach with 10 algorithms, we developed a SARS-CoV-2 score (Cov-2S) signature across The Cancer Genome Atlas and datasets GSE72094, GSE68465, and GSE31210. Comprehensive multi-omics analysis, including assessments of genetic mutations and copy number variations, was conducted to deepen our understanding of the prognosis signature. We also analyzed the response of different Cov-2S subgroups to immunotherapy and identified targeted drugs for these subgroups, advancing personalized medicine strategies. The expression of Cov-2S genes was confirmed through qRT-PCR, with GGH emerging as a critical gene for further functional studies to elucidate its role in LUAD. Results: Out of 34 differentially expressed CRGs identified, 16 correlated with overall survival. We utilized 10 machine learning algorithms, creating 101 combinations, and selected the RFS as the optimal algorithm for constructing a Cov-2S based on the average C-index across four cohorts. This was achieved after integrating several essential clinicopathological features and 58 established signatures. We observed significant differences in biological functions and immune cell statuses within the tumor microenvironments of high and low Cov-2S groups. Notably, patients with a lower Cov-2S showed enhanced sensitivity to immunotherapy. We also identified five potential drugs targeting Cov-2S. In vitro experiments revealed a significant upregulation of GGH in LUAD, and its knockdown markedly inhibited tumor cell proliferation, migration, and invasion. Conclusion: Our research has pioneered the development of a consensus Cov-2S signature by employing an innovative approach with 10 machine learning algorithms for LUAD. Cov-2S reliably forecasts the prognosis, mirrors the tumor's local immune condition, and supports clinical decision-making in tumor therapies.