Investigation of the biocontrol mechanism of a novel Pseudomonas species against phytopathogenic Fusarium graminearum revealed by multi-omics integration analysis.

Phytopathogenic Fusarium graminearum poses significant threats to crop health and soil quality. Although our laboratory-cultivated Pseudomonas sp. P13 exhibited potential biocontrol capacities, its effectiveness against F. graminearum and underlying antifungal mechanisms are still unclear. In light of this, our study investigated a significant inhibitory effect of P13 on F. graminearum T1, both in vitro and in a soil environment. Conducting genomic, metabolomic, and transcriptomic analyses of P13, we sought to identify evidence supporting its antagonistic effects on T1. The results revealed the potential of P13, a novel Pseudomonas species, to produce active antifungal components, including phenazine-1-carboxylate (PCA), hydrogen cyanide (HCN), and siderophores [pyoverdine (Pvd) and histicorrugatin (Hcs)], as well as the dynamic adaptive changes in the metabolic pathways of P13 related to these active ingredients. During the logarithmic growth stage, T1-exposed P13 strategically upregulated PCA and HCN biosynthesis, along with transient inhibition of the tricarboxylic acid (TCA) cycle. However, with growth stabilization, upregulation of PCA and HCN synthesis ceased, whereas the TCA cycle was enhanced, increasing siderophores secretion (Pvd and Hcs), suggesting that this mechanism might have caused continuous inhibition of T1. These findings improved our comprehension of the biocontrol mechanisms of P13 and provided the foundation for potential application of Pseudomonas strains in the biocontrol of phytopathogenic F. graminearum. IMPORTANCE: Pseudomonas spp. produces various antifungal substances, making it an effective natural biocontrol agent against pathogenic fungi. However, the inhibitory effects and the associated antagonistic mechanisms of Pseudomonas spp. against Fusarium spp. are unclear. Multi-omics integration analyses of the in vitro antifungal effects of novel Pseudomonas species, P13, against F. graminearum T1 revealed the ability of P13 to produce antifungal components (PCA, HCN, Pvd, and Hcs), strategically upregulate PCA and HCN biosynthesis during logarithmic growth phase, and enhance the TCA cycle during stationary growth phase. These findings improved our understanding of the biocontrol mechanisms of P13 and its potential application against pathogenic fungi.

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.

MZB1-expressing cells are essential for local immunoglobulin production in chronic rhinosinusitis with nasal polyps.

BACKGROUND: The expression of MZB1 genes is significantly elevated in patients who have chronic rhinosinusitis with nasal polyp (CRSwNP) disease compared with healthy controls. OBJECTIVE: To characterize MZB1-positive B cells in CRSwNP and to estimate the contribution of distinct subsets of B cells to the local overproduction of immunoglobulins. METHODS: Single-cell RNA-sequencing with Cellular Indexing of Transcriptomes and Epitopes by Sequencing technology, Switching Mechanism At the 5' end of RNA Template sequencing, flow cytometry, immunohistochemistry and immunofluorescence staining, Western blot, QuantiGene Plex assay, B-cell ImmunoSpot assay, Luminex assay, and enzyme-linked immunosorbent assay were performed. RESULTS: Significantly higher mRNA expression of MZB1 and HSP90B1 was found in type 2 CRSwNP compared with controls. In CRSwNP, MZB1 expression correlated with the local production of IgE. MZB1 could be colocalized with plasma and mature B cells, especially marginal zone (MZ) B cells. Single-cell transcriptome and epitope studies revealed prominent populations of B cells in type 2 CRSwNP with unexpectedly high MZB1 gene expression. The MZ B-cell population was significantly increased in CRSwNP compared with healthy controls in both peripheral blood mononuclear cells and nasal tissue single-cell suspensions. When those single cells were cultured overnight, the MZ B-cell numbers were positively correlated with local IgE production but negatively correlated with local IgM production. In vitro, MZB1 stimulation up-regulated the mRNA expression of IgE. CONCLUSION: MZB1 was primarily expressed by plasma and mature B cells in nasal mucosa. MZB1 expression level was increased in CRSwNP compared with controls. MZB1 contributed to the local IgE production in type 2 CRSwNP.

Induced Resistance Mechanism of Bacillus velezensis S3-1 Against Pepper Wilt.

In recent years, pepper wilt has emerged as a pivotal constraint on pepper yield augmentation. Bacillus velezensis S3-1, with a wide array of hosts, can be used as both a biocontrol agent and biofertilizer. Nonetheless, the precise mechanisms underpinning its employment in combating pepper wilt remain cloaked in ambiguity. In our study, we found that B. velezensis S3-1 could significantly inhibit Fusarium sp. F1T that caused pepper wilt. S3-1 could effectively inhibit both the growth and germination of F1T conidia, leading to a reduction in the spore germination percentage from 83.2 to 37.1% in vitro experiments. Additionally, leaf detachment experiments revealed that the volatile compounds produced by S3-1 could inhibit the spread of pepper leaf spot area. Moreover, we observed a significant decrease in the content of malondialdehyde (MDA) in pepper treated with S3-1, along with a significant increase in the content of soluble protein, polyphenol oxidase (PPO), peroxidase (POD), and phenylalanine ammonia-lyase (PAL) in pepper. Furthermore, RT-PCR analysis showed that the expression of the defense genes CaPR 1 and CaPIN II in pepper after treatment with S3-1 was significantly upregulated, suggesting that S3-1 had the potential to induce systemic resistance in pepper, thereby enhancing its disease resistance. Hence, our findings suggest that S3-1 can be a promising biocontrol agent for managing pepper wilt in modern agriculture.

The multi-omics single-cell landscape of sinus mucosa in uncontrolled severe chronic rhinosinusitis with nasal polyps.

Uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with elevated levels of type 2 inflammatory cytokines and raised immunoglobulin concentrations in nasal polyp tissue. By using single-cell RNA sequencing, transcriptomics, surface proteomics, and T cell and B cell receptor sequencing, we found the predominant cell types in nasal polyps were shifted from epithelial and mesenchymal cells to inflammatory cells compared to nasal mucosa from healthy controls. Broad expansions of CD4 T effector memory cells, CD4 tissue-resident memory T cells, CD8 T effector memory cells and all subtypes of B cells in nasal polyp tissues. The T and B cell receptor repertoires were skewed in NP. This study highlights the deviated immune response and remodeling mechanisms that contribute to the pathogenesis of uncontrolled severe CRSwNP. CLINICAL IMPLICATIONS: We identified differences in the cellular compositions, transcriptomes, proteomes, and deviations in the immune profiles of T cell and B cell receptors as well as alterations in the intercellular communications in uncontrolled severe CRSwNP patients versus healthy controls, which might help to define potential therapeutic targets in the future.

A novel inflammatory endotype diagnostic model based on cytokines in chronic rhinosinusitis with nasal polyps.

Background: Type 2 CRSwNP is characterized by severe symptoms, multiple comorbidities, longer recovery course and high recurrence rate. A simple and cost-effective diagnostic model for CRSwNP endotype integrating clinical characteristics and histopathological features is urgently needed. Objective: To establish a clinical diagnostic model of inflammatory endotype in CRSwNP based on the clinical characteristics, pathological characteristics, and cytokines profile in the polyp tissue of patients. Methods: A total of 244 participants with CRSwNP were enrolled at 2 different centers in China and Belgium from 2018 to 2020. IL-5 level of nasal polyp tissue was used as gold standard. Clinical characteristics were used to establish diagnostic models. The area under the receiver operating curve (AUC) was used to evaluate the diagnostic performance. The study was approved by the ethics board of the First Affiliated Hospital of Sun Yat-sen University ([2020] 302), and written informed consent was obtained from all subjects before inclusion. Results: In total, 134 patients from China (training set) and 110 patients from Belgium (validation set) were included. The logistic regression (LR) model in predicting inflammatory endotype of CRSwNP showed the AUC of 83%, which was better than the diagnostic performance of machine learning models (AUC of 61.14%-82.42%), and single clinical variables. We developed a simplified scoring system based on LR model which shows similar diagnostic performance to the LR model (P = 0.6633). Conclusion: The LR model in this diagnostic study provided greater accuracy in prediction of inflammatory endotype of CRSwNP than those obtained from the machine learning model and single clinical variable. This indicates great potential for the use of diagnostic model to facilitate inflammatory endotype evaluation when tissue cytokines are unable to be measured.

Pathophysiology and management of Staphylococcus aureus in nasal polyp disease.

INTRODUCTION: Staphylococcus aureus (S. aureus) is a common pathogen that frequently colonizes the sinonasal cavity. Recent studies demonstrated the essential role of Staphylococcus aureus in the pathophysiology of uncontrolled severe chronic rhinosinusitis with nasal polyps (NP) by initiating an immune response to the germ and its products, resulting in type 2 inflammation. AREAS COVERED: This review aims to summarize the evidence for the role of S. aureus in the development of NP disease including S. aureus-related virulence factors, the pathophysiologic mechanisms used by S. aureus, and the synergistic effects of S. aureus and other pathogens. It also describes the current management of S. aureus associated with NPs as well as potential therapeutic strategies that are used in clinical practice. EXPERT OPINION: S. aureus is able to damage the nasal mucosal epithelial barrier, impair the clearance of the host immune system, and trigger adaptive and innate immune reactions which lead to the formation of inflammation and nasal polyp growth. Further studies should focus on the development of novel therapeutic strategies, such as biologics, bacteriophages, probiotics, and nanomedicine, which could be used to treat S. aureus and its immunological consequences in the future.

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.

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.

Source discrimination of mine water based on the random forest method.

Machine learning is one of the widely used techniques to pattern recognition. Use of the machine learning tools is becoming a more accessible approach for predictive model development in preventing engineering disaster. The objective of the research is to for estimation of water source using the machine learning tools. Random forest classification is a popular machine learning method for developing prediction models in many research settings. The type of mine water in the Pingdingshan coalfield is classified into surface water, Quaternary pore water, Carboniferous limestone karst water, Permian sandstone water, and Cambrian limestone karst water. Each type of water is encoded with the number 0-4. On the basis of hydrochemical data processing, a random forests model is designed and trained with the hydrochemical data. With respect to the predictive accuracy and robustness, fourfold cross-validation (CV) is adopted for the model training. The results show that the random forests model presented here provides significant guidance for the discrimination of mine water.

Prediction of elevation of substantial fluctuation in coal seam floor based on surface spline function and its derivative.

With the increasing depth of coal mining, the geological stress and structure becomes more and more complex. The elevation of No.8 coal floor significantly undulates in the studied coal mine. Even though a lot of boreholes have been drilled, it remains difficult to predict the spatial distribution features and it becomes challenging to plan the tunnel for the working face. Consequently, there has been a great loss of production in the coal mine, therefore, it is of great significance to study the prediction method for coal floor elevation of the working face. The surface spline function can be regarded as an infinite flat plate deformation in pure bending. The fluctuation of the coal floor can be considered to be the result of multi-period tectonic stress applied on the coal seam, so, the prediction of elevation of the coal floor with surface spline method is feasible. An advantage of surface spline method is that any order differentiable smooth surface can be obtained without regular known lattice and boundary derivatives. In the paper, the complete expression of surface spline function is derived, which is used to predict the elevation of No.8 coal floor of the coal mine. The results show that the trend of elevation of the coal floor can be extrapolated by known data, and the maximum error is 20 m, the minimum error is 0 m, and the error of 80% of the data is less than 3 m. The general trend of the coal floor has been predicted well. However, local peaks and valleys could not be predicted correctly, therefore, the first and second order derivative are projected to predict the peaks and valleys in the head of the tunneling.

Advances in chronic rhinosinusitis in 2020 and 2021.

Major progress has been achieved in the understanding and clinical practice of chronic rhinosinusitis, with or without nasal polyps. These advances resulted in a better understanding of the pathophysiology, the distribution into subgroups, and consequently in a better management perspective using classical approaches and biologics. Pathomechanisms, endotypes and biomarkers, and finally innovative therapeutic approaches are themes especially for the more severe forms of chronic rhinosinusitis, those with uncontrolled severe nasal polyps. Biologicals against key type 2 cytokines are gaining ground in the long-term treatment approaches of often recurrent nasal polyps, and should be integrated in care pathways making use of classical and innovative treatment pathways. These areas of interest show a fast development and will profoundly change our disease management within a decade.

The Development of the Mucosal Concept in Chronic Rhinosinusitis and Its Clinical Implications.

In the last 2 decades, an increasing understanding of pathophysiological mechanisms in chronic rhinosinusitis (CRS) opened an avenue from phenotyping to endotyping, from eosinophilic inflammation to type 2 immunity, and from the ventilation and drainage paradigm to the mucosal concept for therapeutic considerations. With the advent of type 2 endotyping and targeted biomarkers, precise endotype-driven therapeutic options are possible including biologics and adapted surgical approaches. We here aim to focus on the complexity and heterogeneity of the features of CRS endotypes, especially for those with nasal polyps, including its history, latest developments, clinical associations, and endotype-driven solutions. In order to better manage uncontrolled severe CRS in clinical practice, medical decisions based on a profound understanding of the pathology and immunology of this heterogeneous disease, aiding a precision-medicine based approach for patient's treatment, are pivotal.

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.

Effects of signaling pathway inhibitors on hematopoietic stem cells.

While there are numerous small molecule inhibitory drugs available for a wide range of signalling pathways, at present, they are generally not used in combination in clinical settings. Previous reports have reported that the effects of glycogen synthase kinase (GSK)3ß, p38MAPK, mTOR and histone deacetylase signaling combined together to suppress the stem­like nature of hematopoietic stem cells (HSCs), driving these cells to differentiate, cease proliferating and thereby impairing normal hematopoietic functionality. The present study aimed to determine the effect of HDACs, mTOR, GSK­3ß and p38MAPK inhibitor combinations on the efficient expansion of HSCs using flow cytometry. Moreover, it specifically aimed to determine how inhibitors of the GSK3ß signaling pathway, in combination with inhibitors of P38MAPK and mTOR signaling or histone deacetylase (HDAC) inhibitors, could affect HSC expansion, with the goal of identifying novel combination strategies useful for the expansion of HSCs. The results indicated that p38MAPK and/or GSK3ß inhibitors increased Lin­ cell and Lin­Sca­1+c­kit+ (LSK) cell numbers in vitro. Taken together, these results suggested that a combination of p38MAPK and GSK3ß signaling may regulate HSC differentiation in vitro. These findings further indicated that the suppression of p38MAPK and/or GSK3ß signalling may modulate HSC differentiation and self­renewal to enhance HSC expansion.

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.

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.

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.