Outcomes of endoscopic sinus surgery in patients with central compartment atopic disease.

Background: Central compartment atopic disease (CCAD) is a subtype of chronic rhinosinusitis (CRS). Research focusing on the endoscopic sinus surgery (ESS) outcomes of CCAD is limited. This study aimed to evaluate the outcomes of ESS in CCAD and compared to 2 following subtypes: chronic rhinosinusitis with nasal polyps (CRSwNP) and concomitant polypoid disease in the central compartment (CRSwNP/CC) and CRSwNP not otherwise specified (CRSwNP NOS). Methods: This case-control study enrolled patients with bilateral CRSwNP who underwent ESS and had at least 1 year of follow-up. Patients were classified into CCAD, CRSwNP/CC, and CRSwNP NOS. The demographic data, preoperative disease severity, and surgery outcomes, including CRS control status, endoscopic score, and symptom scores at 1 year postoperatively, were collected. We defined well controlled and partly controlled as appropriate disease control. Results: This study screened 259 patients and enrolled 138 patients with complete medical records and 1-year follow-up (CCAD N = 51, CRSwNP/CC N = 55, CRSwNP NOS N = 32). Among them, appropriate disease control was achieved in 84.3% of patients (43/51) in the CCAD group, 69.1% (38/55) in the CRSwNP/CC group, and 93.7% (30/32) in the CRSwNP NOS group (P = 0.029). Then we performed post-hoc analysis using appropriate disease control and uncontrolled. There was a significant difference between CRSwNP/CC and CRSwNP NOS (P = 0.007), but no significant difference compared CCAD group to CRSwNP/CC group (P = 0.065) and CRSwNP NOS group (P = 0.199). There were significant differences in endoscopic E-score among groups (P < 0.001). In post-hoc analysis, we found that CRSwNP/CC (Median [IQR], 33.32 [42.14]) had a significantly worse E-score than CCAD (8.33 [16.67]) and CRSwNP NOS (4.17 [8.30]). Also, postoperative olfactory visual analog scale (VAS) scores significantly differed among groups (P = 0.043). However, post-hoc analysis showed no difference between any 2 groups. There were no differences in postoperative VAS scores of obstruction (P = 0.159), rhinorrhea (P = 0.398), and headache/facial pain (P = 0.092). Conclusion: Most CCAD patients had good surgical outcomes 1 year after surgery. Meanwhile, the CRSwNP/CC group had the fewest patients under appropriate disease control.

Epithelium-derived kallistatin promotes CD4+ T-cell chemotaxis to TH2-type inflammation in chronic rhinosinusitis.

BACKGROUND: The function of kallistatin in airway inflammation, particularly chronic rhinosinusitis with nasal polyps (CRSwNP), has not been elucidated. OBJECTIVE: We sought to investigate the role of kallistatin in airway inflammation. METHODS: Kallistatin and proinflammatory cytokine expression levels were detected in nasal polyps. For the in vivo studies, we constructed the kallistatin-overexpressing transgenic mice to elucidate the role of kallistatin in airway inflammation. Furthermore, the levels of plasma IgE and proinflammatory cytokines in the airways were evaluated in the kallistatin-/- rat in vivo model under a type 2 inflammatory background. Finally, the Notch signaling pathway was explored to understand the role of kallistatin in CRSwNP. RESULTS: We showed that the expression of kallistatin was significantly higher in nasal polyps than in the normal nasal mucosa and correlated with IL-4 expression. We also discovered that the nasal mucosa of kallistatin-overexpressing transgenic mice expressed higher levels of IL-4 expression, associating to TH2-type inflammation. Interestingly, we observed lower IL-4 levels in the nasal mucosa and lower total plasma IgE of the kallistatin-/- group treated with house dust mite allergen compared with the wild-type house dust mite group. Finally, we observed a significant increase in the expression of Jagged2 in the nasal epithelium cells transduced with adenovirus-kallistatin. This heightened expression correlated with increased secretion of IL-4, attributed to the augmented population of CD4+CD45+Notch1+ T cells. These findings collectively may contribute to the induction of TH2-type inflammation. CONCLUSIONS: Kallistatin was demonstrated to be involved in the CRSwNP pathogenesis by enhancing the TH2 inflammation, which was found to be associated with more expression of IL-4, potentially facilitated through Jagged2-Notch1 signaling in CD4+ T cells.

Unraveling the Molecular Mechanisms of Tomatoes' Defense against Botrytis cinerea: Insights from Transcriptome Analysis of Micro-Tom and Regular Tomato Varieties.

Botrytis cinerea is a devastating fungal pathogen that causes severe economic losses in global tomato cultivation. Understanding the molecular mechanisms driving tomatoes' response to this pathogen is crucial for developing effective strategies to counter it. Although the Micro-Tom (MT) cultivar has been used as a model, its stage-specific response to B. cinerea remains poorly understood. In this study, we examined the response of the MT and Ailsa Craig (AC) cultivars to B. cinerea at different time points (12-48 h post-infection (hpi)). Our results indicated that MT exhibited a stronger resistant phenotype at 18-24 hpi but became more susceptible to B. cinerea later (26-48 hpi) compared to AC. Transcriptome analysis revealed differential gene expression between MT at 24 hpi and AC at 22 hpi, with MT showing a greater number of differentially expressed genes (DEGs). Pathway and functional annotation analysis revealed significant differential gene expression in processes related to metabolism, biological regulation, detoxification, photosynthesis, and carbon metabolism, as well as some immune system-related genes. MT demonstrated an increased reliance on Ca2+ pathway-related proteins, such as CNGCs, CDPKs, and CaMCMLs, to resist B. cinerea invasion. B. cinerea infection induced the activation of PTI, ETI, and SA signaling pathways, involving the modulation of various genes such as FLS2, BAK1, CERK1, RPM, SGT1, and EDS1. Furthermore, transcription factors such as WRKY, MYB, NAC, and AUX/IAA families played crucial regulatory roles in tomatoes' defense against B. cinerea. These findings provide valuable insights into the molecular mechanisms underlying tomatoes' defense against B. cinerea and offer potential strategies to enhance plant resistance.

Therapeutic potential of recombinant human basic fibroblast growth factor on postoperative patients with chronic rhinosinusitis with nasal polyps.

OBJECTIVES: To explore the effect of intranasal administration of recombinant human basic fibroblast growth factor (rh-bFGF) on postoperative chronic rhinosinusitis with nasal polyps (CRSwNP) patients. DESIGN: A prospective, randomised, controlled, single-blinded trial. SETTING AND PARTICIPANTS: Seventy-five hospitalised patients who met the criteria of primary bilateral CRSwNP were enrolled from March 2020 to January 2021. MAIN OUTCOME MEASURES: Visual analogue scale, 22-item Sino-Nasal Outcome Test, Lund-Kennedy (L-K) system and scanning electron microscopy and quantitative real-time polymerase chain reaction. RESULTS: Seventy-five patients with CRSwNP were randomly assigned to three groups, and 72 patients completed the 1-month medication regimen and 1-year follow-up. Rh-bFGF nasal-spray and drop application reduced general nasal VAS scores within 2 weeks after endoscopic sinus surgery (ESS) compared to the control group. In contrast, only rh-bFGF nasal-drops reduced SNOT-22 scores at 2 weeks and 1 year compared with the control group. A significant reduction in the endoscopic L-K score was observed in the rh-bFGF nasal-spray and drop group compared with the control group. This is primarily because rh-bFGF promotes cilia growth in the nasal mucosal epithelium after the operation, as illustrated by scanning electron microscopy and expression of CP110, Tap73 and Foxj1 mRNA. For eosinophilic CRSwNP, the general VAS score of rh-bFGF nasal-drops was more obviously reduced compared to the control group after ESS. A similar trend was observed for L-K score. CONCLUSIONS: Rh-bFGF nasal-drops and sprays can quickly and effectively relieve postoperative symptoms and improve long-term prognosis of patients with CRSwNP. Moreover, rh-bFGF nasal-drops is also an effective method for postoperative patients with eosinophilic CRSwNP.

Short-term postoperative efficacy of steroid-eluting stents for eosinophilic chronic rhinosinusitis with nasal polyps: A randomized clinical trial.

BACKGROUND: Eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP) is a refractory clinical phenotype with a high symptom burden and relapse rate. Steroid-eluting stents are safe and effective for reducing polyp size, symptom burden, and the need for revision sinus surgery. In this study we aimed to evaluate the efficacy and safety of steroid-eluting stent implantation on the surgical outcomes of patients with ECRSwNP. METHODS: This prospective, multicenter, randomized, intrapatient-controlled trial recruited patients 18 to 65 years of age with ECRSwNP who required surgery. Ninety-eight patients were enrolled and randomly implanted with absorbable steroid-eluting stents containing mometasone furoate in one sinus at the end of surgery. All patients received standard postoperative care and follow-up. The primary outcome was the Lund-Kennedy endoscopic score within 12 weeks postsurgery. Secondary outcomes included nasal symptoms scores, nasal resistance, acoustic rhinometry, nasal nitric oxide levels, 3-dimensional volumetric computed tomography scores, and eosinophil counts in the ethmoid mucosa. RESULTS: Ninety-five patients completed the trial. At postoperative weeks 4, 8, and 12, the Lund-Kennedy scores were significantly lower on the treatment side than on the control side (all p < 0.01). Compared with the treatment side, the control side exhibited higher tissue eosinophilia at week 4 and higher volumetric, nasal obstruction, and total nasal symptom scores at postoperative week 8 (p = 0.011, p = 0.011, p < 0.01, and p = 0.001, respectively). No adrenal cortical suppression or serious side effects were observed. CONCLUSION: Steroid-eluting stents reduce postoperative sinus mucosal edema, and eosinophilic inflammation, with persistent effects after stent disintegration, and are a good supplementary postsurgical treatment in patients with ECRSwNP.

Clinical characteristics of central compartment atopic disease in Southern China.

BACKGROUND: Central compartment atopic disease (CCAD) is a newly reported subset of chronic rhinosinusitis. It was considered associated with inhalant antigen. However, CCAD in Chinese population is not fully studied yet. DESIGN: Prospective cohort study. OBJECTIVE: This study aimed to describe the clinical manifestations of CCAD and compared the following two subtypes: sinonasal polyps and concomitant polypoid disease in the central compartment (CRSwNP/CC) and CRSwNP not otherwise specified (CRSwNP NOS). Also, we compared the clinical manifestations of atopy CCAD and non-atopy CCAD. METHODS: We consecutively enrolled CRSwNP patients without prior sinus surgery, and assessed the nasal endoscopy and computed tomography of the paranasal sinuses. Allergy was confirmed by skin or serum testing. Eosinophilic CRSwNP (ECRS) was considered as tissue eosinophils to total inflammatory cells >10%. RESULTS: We enrolled a total of 116 patients, including 39 with CCAD, 38 with CRSwNP/CC and 39 with CRSwNP NOS. Atopy was detected in 37.1% of the CCAD group, an incidence showing no significant difference from those in the other two groups (37.1% in the CRSwNP/CC group, 31.0% in the CRSwNP NOS group; p = 0.846). However, the incidence of ECRS in the CCAD group was the highest among the different groups (97.4% in the CCAD group vs. 67.6% in the CRSwNP/CC group vs. 35.1% in the CRSwNP NOS group; p = 0.000). In addition, the incidence of asthma in the CCAD group (33.3%) was significantly higher than that in the CRSwNP NOS group (10.3%), but quite similar to CRSwNP/CC (34.2%). In the subgroup analysis of CCAD, only total serum IgE and sIgE demonstrated significant differences between atopy CCAD and non-atopy CCAD. CONCLUSION: CCAD in Southern China may associate with asthma and significant eosinophilia, with a lower incidence of systemic allergy based on skin and serum testing.

Risk Factors and Characteristics of the Recurrence of Juvenile Nasopharyngeal Angiofibroma: A 22-Year Experience With 123 Cases at a Tertiary Center.

OBJECTIVES: Despite the efficacy of surgical treatments, the high rate of recurrence in juvenile nasopharyngeal angiofibroma (JNA) after surgery remains an unresolved problem. The present study comprehensively analyzed the risk factors and characteristics of JNA recurrence, providing clinical guidance for reducing recurrence. METHODS: A total of 123 patients who underwent surgery for JNA between 1997 and 2019 at a single hospital were analyzed retrospectively. Univariate and multivariate analyses were used to assess the clinical risk factors for the recurrence of JNA. The relapse-free survival and annual cumulative recurrence rates were analyzed for subgroups defined according to clinical parameters. RESULTS: After screening, 78 of the 123 patients were included in the present study. The main risk factors associated with JNA recurrence included the year of diagnosis, tumor size, sphenoid bone invasion, Radkowski stage, surgical approach, and intraoperative bleeding. Importantly, the surgical approach and sphenoid bone invasion were independent prognostic factors affecting recurrence. Patients who underwent endoscopic surgery without sphenoid bone invasion exhibited longer relapse-free survival. In the present study, the overall cumulative recurrence rate of JNA was 38.7%, and recurrence occurred mainly in the first year after the initial surgery. CONCLUSION: Endoscopic surgery achieved better relapse-free survival in JNA patients, and patients with sphenoid bone invasion should be carefully explored to avoid residual JNA. The recurrence rate of JNA differed among subgroups defined based on clinical parameters and was highest in the first year after surgery. Computed tomography or magnetic resonance imaging, along with close follow-up, should be performed strictly within 1 year after the primary operation.

A novel risk score for disease control prediction of chronic rhinosinusitis.

OBJECTIVES: To assess the impact of risk factors on the disease control among chronic rhinosinusitis (CRS) patients, following 1 year of functional endoscopic sinus surgery (FESS), and combining the risk factors to formulate a convenient, visualised prediction model. DESIGN: A retrospective and nonconcurrent cohort study. SETTING AND PARTICIPANTS: A total of 325 patients with CRS from June 2018 to July 2020 at the First Affiliated Hospital of Sun Yat-sen University, the Third Affliated Hospital of Sun Yat-sen University, the Seventh Affiliated Hospital of Sun Yat-sen University. MAIN OUTCOMES MEASURES: Outcomes were time to event measures: the disease control of CRS after surgery 1 year. The presence of nasal polyps, smoking habits, allergic rhinitis (AR), the ratio of tissue eosinophil (TER) and peripheral blood eosinophil count (PBEC) and asthma was assessed. The logistic regression models were used to conduct multivariate and univariate analyses. Asthma, TER, AR, PBEC were also included in the nomogram. The calibration curve and area under curve (AUC) were used to evaluate the forecast performance of the model. RESULTS: In univariate analyses, most of the covariates had significant associations with the endpoints, except for age, gender and smoking. The nomogram showed the highest accuracy with an AUC of 0.760 (95% CI, 0.688-0.830) in the training cohort. CONCLUSIONS: In this cohort study that included the asthma, AR, TER, PBEC, which had significantly affected the disease control of CRS after surgery. The model provided relatively accurate prediction in the disease control of CRS after FESS and served as a visualised reference for daily diagnosis and treatment.

Age-Associated Changes of Nasal Bacterial Microbiome in Patients With Chronic Rhinosinusitis.

Age-related changes in nasal bacterial microbiota of patients with chronic rhinosinusitis (CRS) remains unclear. In this study, we aimed to identify distinct characteristics of nasal bacterial microbiota between aged and younger patients with CRS through 16S rDNA gene sequencing. Patients with CRS undergoing endoscopic sinus surgery were recruited and separated into aged (≥60 years, median age = 66 years, N = 17) and younger (<60 years, median age = 35.5 years, N = 14) patients. Diversity, bacterial composition and metabolic activities of nasal microbiota between aged and younger patients were compared. Results have shown that levels of OTUs (p = 0.0173) and microbiota diversity (all p < 0.05) decreased significantly in aged patients. The abundance of phylum Actinobacteria, and genus Corynebacterium were significantly higher in aged patients, while the abundance of phylum Bacteroidetes, Fusobacteria, and genus Fusobacterium, Peptoniphilus were significantly higher in younger patients. In addition, predicted functional profiles have revealed that 41 KEGG pathways involving in 12 metabolic pathways, 4 genetic information processing, 3 environmental information processing, 4 cellular processes, 8 organismal systems, 6 human diseases, and 4 unclassified pathways were identified. Among which, the vast majority of metabolic activities are involved in replication and repair, membrane transport, translation, and the metabolism of amino acid, carbohydrate, energy, cofactors and vitamins, and nucleotide. On the level of the thirdly bacterial metabolic pathways, purine metabolism, glycine, serine and threonine metabolism, valine, leucine and isoleucine biosynthesis, glycolysis/gluconeogenesis and phenylalanine, tyrosine and tryptophan biosynthesis are significantly up-regulated while carbon fixation pathways in prokaryotesand methane metabolism are significantly down-regulated in aged patients. Overall, our analysis revealed that age-related physiological and pathological changes on the nasal mucosal surface may alter the host immune response and be highly associated with the nasal bacterial microbiota of patients with CRS. However, future studies are needed to elucidate the causal relationship.

[Delayed cerebrospinal fluid leak post-intensity-modulated radiotherapy for nasopharyngeal carcinoma: a case report].

A 60-year-old man, who diagnosed nasopharyngeal carcinoma staged as T1N1M0 in 2003 and received 68 Gy 30 times intensity modulated radiotherapy for primary tumor, was diagnosed as "cerebrospinal fluid rhinorrhea（left side）; purulent meningitis; nasopharyngeal carcinoma（post-radiotherapy） " in 2017. The patient received an emergency repair of the cerebrospinal fluid leakage by nasal endoscope approach surgery. No rhinorrhea complained in the following 2 years. But two years later, the patient complained a recurrent rhinorrhea by no incentives. The CT scan found ethmoid-like defect change in bottom of the right sphenoid sinus bone this time and no tumor recurrence was observed in CT scan or MRI exam. Then the patient received a second time right-side endoscopic transphenoid approach cerebrospinal fluid leakage repair operation. The patient recovered well after operation and regular endoscope follow-up showed no evidence of cerebrospinal fluid rhinorrhea. This case showed that the risk of cerebrospinal fluid leakage should be considered by the use of intensity modulated radiotherapy. For the cerebrospinal fluid rhinorrhea caused by osteonecrosis after radiotherapy, emergency surgical treatment is required since conservative treatment may not be effective.

The changes of clinical and histological characteristics of chronic rhinosinusitis in 18 years: Was there an inflammatory pattern shift in southern China?

BACKGROUND: Nowadays, the heterogeneity of chronic rhinosinusitis (CRS) has attracted extensive attention. The histological patterns and clinical characteristics may vary greatly in different areas and among different groups of people. Prior studies found a shift from the neutrophilic inflammatory pattern to the eosinophilic inflammatory pattern in Asian cities. This study set out with the aim of investigating the changes that have occurred in the past 18 years of southern China and exploring the causes. METHODS: Tissues, clinical, and demographic characteristics were obtained from 473 patients (91 in 2000-2001, 170 in 2010-2011, 212 in 2017-2018) who satisfied the criteria of diffuse (bilateral) chronic rhinosinusitis. The clinical characteristics, including the previous history of allergic rhinitis and asthma, and the major symptoms of rhinosinusitis, were collected. Formalin-fixed nasal tissue was obtained from each patient for calculating inflammatory cells. We also performed immunohistochemistry to evaluate the expression levels of eosinophilic cationic protein (ECP), IgE, myeloperoxidase (MPO), and other Type 1, Type 2, and Type 3 related inflammatory cytokines. RESULTS: The comorbidity of asthma and atopic disease was higher in 2017-2018 compared to 2000-2001. The histological characteristics revealed a significant increase in tissue eosinophils and decrease in neutrophils in 2017-2018 as compared with 2000-2001. Meanwhile, the proportion of eosinophilic CRS (eCRS) increased significantly from 2000 to 2001 to 2017-2018 (P = 0.03). The tissue eosinophil increase was higher in overweight patients (Body Mass Index, BMI≥24) as compared with non-overweight. There was an increasing trend of ECP, IL-13 and IL-17. Besides, IFN-γ and TNF-α decreased. CONCLUSIONS: There was an eosinophilic shift of diffuse rhinosinusitis inflammatory pattern in southern China over the last 18 years. The proportion of eCRS and difficult-to-treat rhinosinusitis has steadily increased, which is associated with the increase of Type 2, Type 3 cytokines and the decrease of Type 1 cytokines. This study also provided firstly evidence of a strong relationship between overweight and eosinophil shift in the southern Chinese population.

A novel nomogram to predict the overall survival in esthesinoeroblastoma.

BACKGROUND: Increasing evidence indicates that the pathology and the modified Kadish system have some influence on the prognosis of esthesioneuroblastoma (ENB). However, an accurate system to combine pathology with a modified Kadish system has not been established. METHODS: This study aimed to set up and evaluate a model to predict overall survival (OS) accurately in ENB, including clinical characteristics, treatment and pathological variables. We screened the information of patients with ENB between January 1, 1976, and December 30, 2016 from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program as a training cohort. The validation cohort consisted of patients with ENB at Sun Yat-sen University Cancer Center and The First Affiliated Hospital of Sun Yat-sen University in the same period, and 87 patients were included. The Pearson's chi-squared test was used to assess significance of clinicopathological and demographic characteristics. We used the Cox proportional hazards model to examine univariate and multivariate analyses. The model coefficients were used to calculate the Hazard ratios (HR) with 95% confidence intervals (CI). Prognostic factors with a p-value < 0.05 in multivariate analysis were included in the nomogram. The concordance index (c-index) and calibration curve were used to evaluate the predictive power of the nomogram. RESULTS: The c-index of training cohort and validation cohort are 0.737 (95% CI, 0.709 to 0.765) and 0.791 (95% CI, 0.767 to 0.815) respectively. The calibration curves revealed a good agreement between the nomogram prediction and actual observation regarding the probability of 3-year and 5-year survival. We used a nomogram to calculate the 3-year and 5-year growth probability and stratified patients into three risk groups. CONCLUSIONS: The nomogram provided the risk group information and identified mortality risk and can serve as a reference for designing a reasonable follow-up plan.

miR-223-3p Inhibits Antigen Endocytosis and Presentation and Promotes the Tolerogenic Potential of Dendritic Cells through Targeting Mannose Receptor Signaling and Rhob.

BACKGROUND: The role of miR-223-3p in dendritic cells (DCs) is unknown. This study is aimed at investigating the effect of miR-223-3p on the antigen uptake and presentation capacities of DCs and the underlying molecular mechanism. METHODS: FITC-OVA antigen uptake and cell surface markers in bone marrow-derived DCs (BMDCs) were analyzed by flow cytometry. BMDCs were transfected with the miR-223-3p mimic or inhibitor. Cytokine levels were determined by ELISA. CD4+ T cell differentiation was determined by mixed lymphocyte culture assay. RESULTS: OVA treatment significantly downregulated miR-223-3p in BMDCs. The miR-223-3p mimic significantly inhibited OVA-induced antigen uptake and surface expression of MHC-II on BMDCs (P < 0.01). The miR-223-3p mimic increased TGF-ß1 production in OVA-treated DCs (P < 0.01). Mixed lymphocyte reaction showed that the miR-223-3p mimic significantly promoted Treg cell differentiation. In addition, the miR-223-3p mimic significantly upregulated CD103 in DCs, indicating the promotion of tolerogenic DCs. The miR-223-3p mimic downregulated Rhob protein in OVA-induced DCs. Rhob knockdown significantly suppressed the ability of FITC-OVA endocytosis (P < 0.01) and surface MHC-II molecule expression (P < 0.01) in BMDCs, promoting promoted Treg cell differentiation. Mannose receptor (MR) knockdown significantly upregulated miR-223-3p, downregulated Rhob protein in OVA-treated DCs, inhibited the FITC-OVA endocytosis and surface MHC-II expression in BMDCs, and promoted Treg cell differentiation (all P < 0.01). CONCLUSION: These data suggest that miR-223-3p has an inhibitory effect on the antigen uptake and presentation capacities of BMDCs and promotes Treg cell differentiation, which is, at least partially, through targeting MR signaling and Rhob.

Effect of short-course glucocorticoid application on patients with chronic rhinosinusitis with nasal polyps.

BACKGROUND: Local and systemic glucocorticoids are mainstay therapies for chronic rhinosinusitis. With respect to local glucocorticoids, nasal spray is used extensively, but some patients do not benefit from short-course treatment. Recently, some clinicians have focused on the effects of high-dose local glucocorticoids in chronic rhinosinusitis with nasal polyps (CRSwNP), such as treatment using nasal irrigation, transnasal nebulization, and nose-dripping therapy (nasal drop) with high-dose budesonide. However, there are little data comparing the effect of short-course high-dose local glucocorticoids with regular nasal spray and oral steroids in the treatment of preoperative CRSwNP patients. Furthermore, the appropriate use of different types of glucocorticoids in different endotypes of CRSwNP remains unclear. METHODS: This randomized controlled clinical research study was performed at a single academic center. Patients who satisfied the criteria of chronic rhinosinusitis with bilateral nasal polyps were randomly assigned in a 1:1:1 ratio to receive oral methylprednisolone, 24 mg/d and budesonide nasal spray, 256 µg/d, or intranasal budesonide suspension, 1 mg/d and budesonide nasal spray, 256 µg/d, or budesonide nasal spray, 256 µg/d for one week. Symptoms, endoscopic scores, and tissue and blood inflammatory cells were recorded before and after the study. Adverse events were recorded by clinicians. RESULTS: A total of 127 patients with CRSwNP underwent randomization. The total nasal symptoms scores (TNSS) decreased significantly in all groups compared to those at baseline. The assessment of the reduction in TNSS demonstrated that the change was significantly greater in the nasal drop group than in the nasal spray group (-7.47 vs -4.10, P = 0.032), and it was also greater in the oral steroid group than in the nasal spray group (-7.30 vs -4.10, P = 0.039). A similar trend also appeared in the reduction in Sinonasal-Outcome Test 22 (SNOT-22). After treatment, a significantly reduction in NP score was observed in the nasal drop group (-0.82) and oral steroid group (-0.85) compared with that in the nasal spray group (-0.10), and there was no significant difference between the nasal drop and oral steroid groups (P = 0.98). While calculating the percentage of patients who were sensitive to glucocorticoid treatment, there was 10.26% in the nasal spray group, 47.37% in the nasal drop group, and 52.50% in the oral steroid group that were sensitive to glucocorticoid treatment. The reduction in NP score was more significant in patients with eosinophilic CRSwNP in the nasal drop group and oral steroid group than in the nasal spray group. However, in patients with non-eosinophilic CRSwNP, the change in NP size was similar in the different treatment groups. CONCLUSION: Budesonide suspension nasal drop can significantly improve the quality of life and reduce the endoscopic score following short-course treatment, and the treatment effect of nasal drop was better than that of regular nasal spray. Budesonide nasal suspension can be used as a regular treatment for eosinophilic CRSwNP and can be an alternative choice for patients with a high percentage of tissue eosinophil infiltration who cannot use oral glucocorticoids.

Proteomics profiling of epithelium-derived exosomes from nasal polyps revealed signaling functions affecting cellular proliferation.

BACKGROUND: Nasal polyps are a significantly associated pathology of chronic rhinosinusitis (CRS) whose mechanisms of pathogenesis are not fully elucidated, especially the interaction of the polyp with its environment that allows its growth on the nasal epithelial lining. Exosomes are nanovesicles that serve important biological functions, including cell-to-cell signaling and communication. OBJECTIVE: Hence, we sought to explore the roles of the epithelial-derived exosomal proteome obtained from the human nasal epithelium in the modulation of CRS with nasal polyp (CRSwNP) pathogenesis. METHODS: We sampled exosomes from nasal lavage fluid and primary human nasal epithelial cells (hNECs) from healthy controls and patients with CRSwNP with and without coexisting asthma. The presence of exosomes was confirmed using a NanoSight assay, transmission electron microscopy and western blotting. The exosomal proteome was profiled with mass spectrometry. The Cell Counting Kit-8 was used to confirm the roles of exosomes in mediating cellular proliferation. RESULTS: The hNEC-derived exosomes from diseased epithelium contained differentially expressed proteins that were mainly involved in epithelial remodeling via pathways such as p53. An in vitro study further demonstrated that epithelial-derived exosomes from patients with CRSwNP (with and without coexisting asthma) significantly reduced the rate of proliferation of control hNECs at an effective concentration of ≥10 µg/ml. CONCLUSIONS: Exosomes secreted by hNECs from patients with CRSwNP, regardless of their coexistence with asthma, are laden with proteins that influence cell proliferation pathways, potentially leading to remodeling of the sinonasal mucosa.

MiR-146a Promotes Tolerogenic Properties of Dendritic Cells and through Targeting Notch1 Signaling.

BACKGROUND: MiR-146a has been shown to negatively regulate innate immune, inflammatory response and antiviral pathway, however, its role in the tolerogenic responses remains largely unknown. This study aimed to investigate the role of miR-146a in the OVA-induced allergic inflammation of dendritic cells (DCs). METHODS: Bone marrow-derived DCs (BMDCs) were treated with OVA (100 µg/ml) for 24 h. MiR-146a expressions were assessed by quantitative RT-PCR. BMDCs were transfected with miR-146a mimics or inhibitor. Cell surface markers were analyzed by flow cytometry. Cytokine levels were determined by ELISA assay. Mixed lymphocyte culture assay was adopted to assess CD4 + T-cell differentiation. The 3' UTR luciferase reporter assay was utilized to determine the miRNA target sequence. RESULTS: OVA treatment significantly up-regulated miR-146a in BMDCs in a dose- and time-dependent manner. In the OVA-treated DCs, overexpression of miR-146a (mimics transfection) down-regulated the surface markers (CD80, CD86) and increased production of anti-inflammatory cytokines TGF-ß1 and IL-10 but decreased pro-inflammatory cytokine IL-12. MiR-146a overexpression promoted immature DC to induce regulatory T cells (Treg) differentiation. By contrast, transfection of miR-146a inhibitor into DC exhibited the opposite trends. Notch1 was a direct target of miR-146a, and Notch1 knock-down induced similar effects as miR-146a mimics transfection in BMDCs. Moreover, the effect of miR-146a inhibitor on OVA-induced DC was attenuated by Notch1 knock-down. CONCLUSION: miRNA-146a promoted tolerogenic properties of DCs, at least partially, through targeting Notch1 signaling.

Quality analysis of smart phone sleep apps in China: can apps be used to conveniently screen for obstructive sleep apnea at home?

BACKGROUND: Obstructive sleep apnea (OSA) is a sleep disorder with a high prevalence in China. Standard diagnosis of OSA requires polysomnography (PSG). Currently, smart phone applications (apps) are widely used as an important source of health guidance. However, the quality of the information provided by these apps has not been carefully assessed. METHODS: We searched for sleep apps available in China. We designed an evaluation scale that included scientific, functionality and usability, and accountability domains. The Scientific domain included an index of 16 items to evaluate the scientific quality of the apps for their level of adherence to PSG. The functionality and usability domain included 10 items to evaluate the functions of apps and 1 item to define whether the apps needed to connect with other devices. The accountability domain included 9 items that came from the Silberg Scale to evaluate whether the information provided by apps were trustable or not. We then calculated the sum of all domains. We also evaluated the popularity of each app. RESULTS: A total of 2379 apps were found, and 127 met the inclusion criteria. The mean total score of the apps was 14.23 ± 3.93. The mean scores of scientific basis, functionality and usability, and accountability were 5.51 ± 2.58, 2.90 ± 1.84, and 2.90 ± 1.84. The scientific scores of apps that could connect to other devices were higher than those of apps that worked alone (mean score: 5.26 vs. 4.17, P < 0.001). The functionality and usability score was correlated with the accountability score, and the coefficient of correlation was 0.304 (P = 0.001). CONCLUSIONS: Apps that could connect to other devices were more scientific and powerful than those that worked alone. Multifunctional apps were more popular and reliable. Because of the low quality of sleep apps in China, more work is necessary to create an ideal app.

Concordant systemic and local eosinophilia relates to poorer disease control in patients with nasal polyps.

BACKGROUND: Eosinophilic inflammation is a major phenotype associated with poorly controlled disease in nasal polyp patients. The difference between systemic and local eosinophilia in relation to disease control is poorly understood. OBJECTIVE: To explore whether blood and polyp tissue eosinophil numbers are independent risk factors for poor disease control in patients with nasal polyp. METHODS: By using the electronic medical records database and manual evaluation, 183 nasal polyp patients who had undergone endoscopic sinus surgery at least one year prior to the study with complete data of tissue specimens, baseline blood routine test, nasal endoscopy and sinus computed tomography, were identified and recruited to assess disease control based on the criteria of a European position paper on rhinosinusitis and nasal polyps 2012 (EPOS 2012). Multiple logistic regression model was used to determine the association between blood and tissue eosinophil numbers and risk of poor disease control by adjusting for demographics and comorbidities. RESULTS: We broke down the cohort into 4 groups according to blood (0.3 â€‹× â€‹109/L) and tissue (10%) eosinophils. The patients without eosinophilic inflammation represented the largest group (41.5%). The group with concordant blood and tissue eosinophilia represented the second largest (31.2%), and the patients with isolated tissue (15.3%) or blood (12.0%) eosinophilia were relatively rare. Multiple logistic regression models found blood eosinophil count and tissue eosinophil percentage were independently associated with increased risk for poor disease control after adjustments for covariates related to poor treatment outcome. Furthermore, subjects with concordant blood and tissue eosinophilia had a higher risk for poor disease control than those with isolated blood or tissue eosinophilia. CONCLUSION: Concordant blood and tissue eosinophilia relates to a higher likelihood of poor disease control than isolated blood or tissue eosinophilia after adjustment of potential confounders in nasal polyp patients.

LL-37 promotes neutrophil extracellular trap formation in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Neutrophil accumulation has been observed in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the functions of neutrophils are poorly understood. Neutrophils produce neutrophil extracellular traps (NETs), which are involved in a variety of chronic inflammatory pathologies. LL-37 is the only member of the cathelicidin family in human. OBJECTIVE: Our aims were to examine the presence of NETs in CRSwNP and to investigate the regulatory effect of LL-37 on NET formation. METHODS: Nasal polyp tissues were investigated for the presence of NETs by using immunofluorescent (IF) staining. The expression and distribution of LL-37 were examined by using quantitative RT-PCR, ELISA, IF, and immunohistochemistry. Purified peripheral neutrophils were stimulated with LL-37 and stained with IF to identify NETs. NETs% was defined as percentage of NET-generating neutrophils to the total number of neutrophils. RESULTS: Neutrophil extracellular traps were located in the subepithelial layer of nasal polyps and control tissues. Nasal polyps had higher NETs% compared with that of controls (23.01% ± 3.43% vs 4.52% ± 1.33%, P < 0.0001). NET count was also increased in nasal polyps. NET count correlated with neutrophil count (r = 0.908, P < 0.001). LL-37 protein and mRNA levels were upregulated in nasal polyps. LL-37 was distributed in the epithelial and subepithelial layer and mainly expressed by neutrophils. Moreover, LL-37 promoted peripheral neutrophils to form NETs in a dose-dependent manner ex vivo. Interestingly, dexamethasone did not inhibit the effect of LL-37 on inducing NET formation. Furthermore, peripheral neutrophils from CRSwNP patients were more susceptible to LL-37-mediated NET formation, compared with neutrophils derived from control subjects. In addition, NETs released LL-37 in vivo and ex vivo. CONCLUSION: Neutrophil extracellular traps are significantly increased in nasal polyps and LL-37 induces NET formation in CRSwNP patients. These findings indicate that NETs may contribute to the pathogenesis of neutrophilic inflammation in CRSwNP.