ALOX15+ M2 macrophages contribute to epithelial remodeling in eosinophilic chronic rhinosinusitis with nasal polyps.

BACKGROUND: Epithelial remodeling is a prominent feature of eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP), and infiltration of M2 macrophages plays a pivotal role in the pathogenesis of eCRSwNP, but the underlying mechanisms remain undefined. OBJECTIVE: We aimed to investigate the role of ALOX15+ M2 macrophages in the epithelial remodeling of eCRSwNP. METHODS: Digital spatial transcriptome and single-cell sequencing analyses were used to characterize the epithelial remodeling and cellular infiltrate in eCRSwNP. Hematoxylin and eosin staining, immunohistochemical and immunofluorescent staining were used to explore the relationship between ALOX15+ M2 (CD68+CD163+) macrophages and epithelial remodeling. A co-culture system of primary human nasal epithelial cells (hNECs) and the macrophage cell line THP-1 was used to determine the underlying mechanisms. RESULTS: Spatial transcriptomics analysis showed that upregulation of epithelial remodeling-related genes, such as VIM and MMP10, and enrichment of epithelial-mesenchymal transition (EMT)-related pathways, in the epithelial areas in eCRSwNP, with more abundance of epithelial basal, goblet and glandular cells. Single-cell analysis identified ALOX15+, rather ALOX15-, M2 macrophages were specifically highly expressed in eCRSwNP. CRSwNP with high ALOX15+ M2THP-1-IL-4+IL-13 macrophages had more obvious epithelial remodeling features and increased genes associated with epithelial remodeling and integrity of epithelial morphology versus that with low ALOX15+ M2THP-1-IL-4+IL-13 macrophages. IL-4/13-polarized M2THP-1-IL-4+IL-13 macrophages upregulated expressions of EMT-related genes in hNECs, including VIM, TWIST1, Snail, and ZEB1. ALOX15 inhibition in M2THP-1-IL-4+IL-13 macrophages resulted in reduction of the EMT-related transcripts in hNECs. Blocking CCL13 signaling inhibited M2THP-1-IL-4+IL-13 macrophage-induced EMT alteration in hNECs. CONCLUSION: ALOX15+ M2 macrophages are specifically increased in eCRSwNP and may contribute to the pathogenesis of epithelial remodeling via production of CCL13.

The complete chloroplast genome of Castanopsis hystrix Hook. f. & Thomson ex A. DC. 1863 (Fagaceae).

Castanopsis hystrix Hook. f. & Thomson ex A. DC. 1863 (Fagaceae) is an evergreen broad-leaved tree with high economic and ecological value. In this study, the complete chloroplast genome of C. hystrix was sequenced, assembled and annotated. The plastome (plastid genome) of C. hystrix was 160,624 bp in size, consisting of a pair of inverted repeats (IRs, 25,699 bp), a large-single-copy (LSC, 90,276 bp) region, and a small-single-copy (SSC, 18,950 bp). The overall GC content of C. hystrix was 36.8%. A total of 133 genes were annotated, including 88 protein-coding genes (PCG), 37 transfer RNA genes (tRNA), and eight ribosomal RNA genes (rRNA). A maximum likelihood analysis showed that the Castanopsis species form a monophyletic clade. C. hystrix is most closely related to C. tibetana with 100% bootstrap support value. The result enriches the genomic data for the genus Castanopsis, which will contribute to future studies in phylogenetics and evolution.

Diagnosis and treatment of transnasal endoscopic optic canal decompression for traumatic optic neuropathy.

Objective: To investigate the clinical efficacy and prognostic factors of transnasal endoscopic optic decompression in the treatment of traumatic optic neuropathy (TON). Methods: A retrospective analysis was performed on 13 TON patients in The Seventh Affiliated Hospital of Sun Yat-sen University and Shenzhen Eye Hospital in Shenzhen City (China) from June 2020 to April 2022. These patients had received transnasal endoscopic optic decompression, and hormonal and neurotrophic drugs were given after surgery. Visual acuity (VA) improvement was used as the criterion to judge clinical efficacy. Results: In a total of 13 patients, 13 injured eyes (12 men and 1 woman; mean age, 28.0 ± 11.8 years) received transnasal endoscopic optic decompression. After surgery, nine patients had improved VA, whereas four patients failed to show any improvement, resulting in a total effective rate of 69.2%. Of the six patients with no light perception preoperatively, three had effective results after the operation, giving an effective rate of 50.0%. Of the seven patients with residual light sensation preoperatively, six had effective results after the operation, giving an effective rate of 85.7%. Of the 10 patients operated on within 7 days after injury, seven had effective results, giving an effective rate of 70%. Of the three patients injured and operated on after 7 days, two had effective results, giving an effective rate of 66.7%. Conclusion: Transnasal endoscopic optic nerve decompression is an effective treatment method for TON. The presence of residual light perception and the timing of surgery within 7 days are crucial to the prognosis.

Endotyping Difficult-to-Treat Chronic Rhinosinusitis with Nasal Polyps by Structured Histopathology.

INTRODUCTION: This study aimed to identify the histopathologic characteristics associated with difficult-to-treat chronic rhinosinusitis with nasal polyps (CRSwNPs), enabling physicians to predict the risk of poor outcome after endoscopic sinus surgery (ESS). METHODS: A prospective cohort study performed at the First Affiliated Hospital of Sun Yat-sen University between January 2015 and December 2018 with CRSwNP patients who underwent ESS. Polyp specimens were collected during surgery and were subjected to structured histopathological evaluation. Difficult-to-treat CRSwNPs were determined at 12-15 months post-operation according to the European Position Paper. Multiple logistic regression model was used to assess the association between histopathological parameters and the difficult-to-treat CRSwNP. RESULTS: Among 174 subjects included in the analysis, 49 (28.2%) were classified with difficult-to-treat CRSwNP, which had higher numbers of total inflammatory cells, tissue eosinophils, and percentages of eosinophil aggregates and Charcot-Leyden crystals (CLC) formation but a lower number of interstitial glands than the nondifficult-to-treat CRSwNP. Inflammatory cell infiltration (adjusted OR: 1.017), tissue eosinophilia (adjusted OR: 1.005), eosinophil aggregation (adjusted OR: 3.536), and CLC formation (adjusted OR: 6.972) were independently associated with the difficult-to-treat outcome. Furthermore, patients with tissue eosinophil aggregation and CLC formation had an increasingly higher likelihood of uncontrolled disease versus those with tissue eosinophilia. CONCLUSION: The difficult-to-treat CRSwNP appears to be characterized by increased total inflammatory infiltrates, tissue eosinophilia, eosinophil aggregation, and CLC formation in structured histopathology.

The complete chloroplast genome of Eurya rubiginosa var. attenuata H. T. Chang (Pentaphylacaceae).

Eurya rubiginosa var. attenuata is a valuable multiuse tree with a long history of use in China. It has great economic and ecological importance and is used for landscape and urban planting, soil improvement, and raw materials for food production. However, genomic studies of E. rubiginosa var. attenuata are limited. Meanwhile, the classification of this taxon is controversial. In this study, the complete plastome of E. rubiginosa var. attenuata was successfully sequenced and assembled. The chloroplast genome is 157,215 bp in length with a 37.3% GC content. The chloroplast genome structure includes a quadripartite structure comprising a pair of inverted repeat (IR) sequences of 25,872 bp, a small single-copy (SSC) region of 18,216 bp, and a large single-copy (LSC) region of 87,255 bp. The genome contains 128 genes, including 83 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. Phylogenetic inference based on complete plastome analysis showed that E. rubiginosa var. attenuata is closely related to E. alata and belongs to the family Pentaphylacaceae, which differs from the results of the traditional Engler system. The chloroplast genome sequence assembly and phylogenetic analysis enrich the genetic resources of Pentaphylacaceae and provide a molecular basis for further studies on the phylogeny of the family.

Chinese Expert Consensus on the Use of Biologics in Patients with Chronic Rhinosinusitis (2022, Zhuhai).

BACKGROUND: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. SUMMARY: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. KEY MESSAGES: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

Mapping Topsoil Total Nitrogen Using Random Forest and Modified Regression Kriging in Agricultural Areas of Central China.

Accurate understanding of spatial distribution and variability of soil total nitrogen (TN) is critical for the site-specific nitrogen management. Based on 4337 newly obtained soil observations and 33 covariates, this study applied the random forest (RF) algorithm and modified regression kriging (RF combined with residual kriging: RFK, hereafter) model to spatially predict and map topsoil TN content in agricultural areas of Henan Province, central China. According to the RFK prediction, topsoil TN content ranged from 0.52 to 1.81 g kg-1, and the farmland with the topsoil TN contents of 1.00-1.23 g kg-1 and 0.80-1.23 g kg-1 accounted for 48.2% and 81.2% of the total farmland area, respectively. Spatially, the topsoil TN in the study area was generally higher in the west and lower in the east. By using the Boruta variable selection algorithm, soil organic matter (SOM) and available potassium contents in topsoil, nitrogen deposition, average annual precipitation, livestock discharges, and topsoil pH were identified as the main factors driving the spatial distribution and variation of soil TN in the study area. The RF and RFK models used showed the expected performance and achieved acceptable TN prediction accuracy. In comparison, RFK performed slightly better than the RF model. The R2 and RMSE achieved by the RFK model were improved by 4.5% and 4.5%, respectively, compared with that by the RF model. However, the results suggest that RFK was inferior to the RF model in quantifying prediction uncertainty and thus may have a slight disadvantage in model reliability.

Relationship between Eosinophilic and Neutrophilic Inflammation in Chinese Chronic Rhinosinusitis with Nasal Polyps.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNPs) in China is characterized by a mixed eosinophilic-neutrophilic inflammation, linking to a more heterogeneous clinical phenotype. However, the relationship between eosinophilic and neutrophilic inflammation in Chinese patients with CRSwNP remains largely unknown. We aimed to further characterize the correlation between neutrophils with eosinophils in relation to clinical characters and disease control status after endoscopic sinus surgery (ESS). METHODS: A total of 242 patients were recruited and stratified based on tissue (≥10%) eosinophilia and (≥20/per high-power field) neutrophilia. Clinical characteristics and disease control status were compared between subgroups. Associations between tissue eosinophils and neutrophils were analyzed. RESULTS: The uncontrolled patients accounted for 41.3%, 41.3%, 17.1%, and 22.2% in subjects with concomitant tissue eosinophilia and neutrophilia (EN-high), isolated eosinophilia (E-high), isolated neutrophilia (N-high), and no eosinophilia and neutrophilia (EN-low), respectively. Positive correlations between tissue eosinophils and neutrophils were observed in patients with CRSwNP as well as in EN-high and N-high subgroups but not in E-high and EN-low subgroups. The EN-high subgroup had higher tissue eosinophil numbers than the other three subgroups. Both EN-high and E-high subgroups had higher rates of uncontrolled subjects than the N-high and EN-low subgroups; however, there was no difference in the rate of uncontrolled subjects between EN-high and E-high subgroups and between N-high and EN-low subgroups. CONCLUSION: Tissue neutrophils might have a potential interaction and mutual promotion effect with eosinophils in CRSwNP. However, tissue neutrophilia would not pose significant risk for poor disease control after ESS. Further larger, prospective studies are needed to confirm our findings.

Deep learning-based prediction of treatment prognosis from nasal polyp histology slides.

BACKGROUND: Histopathology of nasal polyps contains rich prognostic information, which is difficult to extract objectively. In the present study, we aimed to develop a prognostic indicator of patient outcomes by analyzing scanned conventional hematoxylin and eosin (H&E)-stained slides alone using deep learning. METHODS: An interpretable supervised deep learning model was developed using 185 H&E-stained whole-slide images (WSIs) of nasal polyps, each from a patient randomly selected from the pool of 232 patients who underwent endoscopic sinus surgery at the First Affiliated Hospital of Sun Yat-Sen University (internal cohort). We internally validated the model on a holdout dataset from the internal cohort (47 H&E-stained WSIs) and externally validated the model on 122 H&E-stained WSIs from the Seventh Affiliated Hospital of Sun Yat-Sen University and the University of Hong Kong-Shenzhen Hospital (external cohort). A poor prognosis score (PPS) was established to evaluate patient outcomes, and then risk activation mapping was applied to visualize the histopathological features underlying PPS. RESULTS: The model yielded a patient-level sensitivity of 79.5%, and specificity of 92.3%, with areas under the receiver operating characteristic curve of 0.943, on the multicenter external cohort. The predictive ability of PPS was superior to that of conventional tissue eosinophil number. Notably, eosinophil infiltration, goblet cell hyperplasia, glandular hyperplasia, squamous metaplasia, and fibrin deposition were identified as the main underlying features of PPS. CONCLUSIONS: Our deep learning model is an effective method for decoding pathological images of nasal polyps, providing a valuable solution for disease prognosis prediction and precise patient treatment.

Endoscopic Endonasal Trans-Agger Nasi Approach for Resection of Ossifying Fibroma Involving the Anterior Skull Base: Surgical Anatomy and Technical Note.

OBJECTIVE: A variety of approaches for resection of the ossifying fibromas in sinonasal cavities have been described. However, for those involving the anterior skull base, endoscopic surgery remains challenging because of limitations in identification of tumor boundaries from the anterior skull base and proper control of the tumor-feeding vessel. This study aimed to describe a technique for resection of ossifying fibromas involving the anterior skull base through an endoscopic endonasal trans-agger nasi approach, based on anatomic studies and surgeries. METHODS: Two human cadaveric heads were prepared for study of the anatomic relationship between agger nasi and anterior skull base. Two clinical cases were used to illustrate the technique and feasibility of the approach. RESULTS: The agger nasi was located anterior and inferior to the frontal ostium and the anterior skull base. The frontal ostium and anterior skull base could be visualized and accessed under the 0-degree endoscope by removing the agger nasi. Application of the endoscopic endonasal trans-agger nasi approach in the two patients resulted in complete resection of the tumors with no surgical complications. CONCLUSIONS: An endoscopic endonasal trans-agger nasi approach provides a direct access to the anterior skull base. It would be feasible, effective, and safe for selected cases of ossifying fibroma involving anterior skull base.

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.

Clinical characteristics of patients with CRSwNP with intensely high eosinophil level.

Background: High tissue and blood eosinophils are linked to poor treatment outcome in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, the difference between the patients with different level of blood or tissue eosinophilia in relation to disease control is still lacking. Objectives: This study aimed to characterize patients with CRSwNP with intensely high eosinophil level. Methods: A retrospective study of CRSwNP patients underwent endoscopic sinus surgery was conducted. The patients were subdivided with various cut-off values of blood and tissue eosinophils. Tissue eosinophils of ≥50% and 10%-20% were defined as intensely high tissue eosinophils (IH-tissue-eos) and high tissue eosinophils (H-tissue-eos), respectively. Blood eosinophils of ≥0.6 × 109/L and 0.2 × 109/L-0.3 × 109/L were defined as intensely high blood eosinophils (IH-blood-eos) and high blood eosinophils (H-blood-eos). Clinical characteristics, Lund-Mackay score (LMS), and disease control status were compared between subgroups. Results: A total of 302 patients were enrolled. There was a trend toward a higher rate of uncontrolled disease when the patients subdivided by blood eosinophil cut-off values ranged from 0.1 × 109/L to 0.6 × 109/L. The controlled patients accounted for 27%, 36%, 22%, and 31%, and the uncontrolled patients 46%, 32%, 52%, and 31% of patients in IH-tissue-eos, H-tissue-eos, IH-blood-eos, and H-blood-eos subgroup, respectively. The percentages of patients in the three categories of control were not significantly different between IH-tissue-eos and H-tissue-eos subgroups. By contrast, the IH-blood-eos subgroup had higher percentages of current smoker and asthma, preoperative LMS and tissue eosinophil percentage, and showed a trend toward a higher rate of uncontrolled subjects compare with the H-blood-eos subgroup. Conclusion: CRSwNP patients with IH-blood-eos (≥0.6 × 109/L) may be possibly associated with a poorer disease control than those with levels near the threshold of blood eosinophilia (0.2 × 109/L-0.3 × 109/L). Further larger, preferably prospective studies are needed to confirm this relationship.Level of Evidence: 4.

Association Between Serum Amyloid A Expression and Disease Control after Endoscopic Sinus Surgery in Patients With Chronic Rhinosinusitis With Nasal Polyps.

OBJECTIVE: Our previous study revealed that serum amyloid A (SAA) levels in polyp tissues could serve as a biomarker for the prediction of corticosteroid insensitivity in patients with chronic rhinosinusitis with nasal polyps (CRSwNP). However, their association with disease control status in the patients after endoscopic sinus surgery remains to be assessed. METHODS: Polyp tissues and control uncinate process mucosa were collected from 48 patients with CRSwNP and 10 healthy control subjects. SAA expression was examined using immunohistochemistry and enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curves were performed to determine the predictive value of SAA in nasal polyps. The clinical characteristics of 2 CRSwNP subtypes (SAAhigh and SAAlow) were evaluated. RESULTS: The SAA expression levels in polyp tissues were significantly elevated both in non-eosinophilic and eosinophilic CRSwNP as compared to the healthy controls. In patients with CRSwNP, the tissue SAA level was significantly higher in the disease-controlled patients than those of the partly controlled and uncontrolled. ROC curve analysis revealed that a cut-off value of 114.9 ng/mL for the tissue SAA level predicted the patients with disease-controlled status with 93.33% sensitivity and 63.64% specificity (AUC = .8727, P < .001). Furthermore, The SAAhigh subgroup showed higher tissue eosinophil numbers and percentage of the disease-controlled patients compared to the SAAlow subgroup. CONCLUSIONS: Our findings suggest that measurements of SAA in polyp tissues may provide useful information for evaluating CRSwNP conditions, especially identifying the CRSwNP patients with disease-controlled status after endoscopic sinus surgery.

Artificial intelligence for cellular phenotyping diagnosis of nasal polyps by whole-slide imaging.

BACKGROUND: artificial intelligence (AI) for cellular phenotyping diagnosis of nasal polyps by whole-slide imaging (WSI) is lacking. We aim to establish an AI chronic rhinosinusitis evaluation platform 2.0 (AICEP 2.0) to obtain the proportion of inflammatory cells for cellular phenotyping diagnosis of nasal polyps and to explore the clinical significance of different phenotypes of nasal polyps on the WSI. METHODS: a total of 453 patients were enrolled in our study. For the development of AICEP 2.0, 179 patients (WSIs) were obtained from the Third Affiliated Hospital of Sun Yat-Sen University (3HSYSU) from January 2008 to December 2018. A total of 24,625 patches were automatically extracted from the regions of interest under a 400× HPF by Openslide and the number of inflammatory cells in these patches was counted by two pathologists. For the application of AICEP 2.0 in a prospective cohort, 158 patients aged 14-70 years old with chronic rhinosinusitis with nasal polyps (CRSwNP) who had undergone endoscopic sinus surgery at 3HSYSU from June 2020 to December 2020 were included for preoperative demographic characteristics. For the application of AICEP 2.0 in a retrospective cohort, 116 patients with CRSwNP who had undergone endoscopic sinus surgery from May 2016 to June 2017 were enrolled for the recurrence rate. The proportion of inflammatory cells of these patients on WSI was calculated by our AICEP 2.0. FINDINGS: for AICEP 2.0, the mean absolute errors of the ratios of eosinophils, lymphocytes, neutrophils, and plasma cells were 1.64%, 2.13%, 1.06%, and 1.22%, respectively. The four phenotypes of nasal polyps were significantly different in clinical characteristics (including asthma, itching, sneezing, total IgE, peripheral eosinophils%, tissue eosinophils%, tissue neutrophils%, tissue lymphocytes%, tissue plasma cells%, and recurrence rate; P <0.05), but there were no significant differences in age distribution, onset time, total VAS score, Lund-Kennedy score, or Lund-Mackay score. The percentage of peripheral eosinophils was positively correlated with the percentage of tissue eosinophils (r = 0.560, P <0.001) and negatively correlated with tissue lymphocytes% (r = -0.489, P <0.001), tissue neutrophils% (r = -0.225, P = 0.005), and tissue plasma cells% (r = -0.266, P = 0.001) in WSIs.

Modified adenoid grading system for evaluating adenoid size in children: a prospective validation study.

Nasal endoscopy is the best choice for evaluation of adenoid size, but very few studies published on the endoscopic quantitative assessment. This study aimed to newly propose and validate a modified adenoid grading system (MAGS) with the existing endoscopic scoring methods of adenoid size. A prospective study on children with chronic mouth breathing and having endoscopic nasal examination was conducted. Digital images obtained during endoscopic examination were evaluated with the traditional method and the MGAS. Adenoid size was also evaluated by intraoperative nasal endoscopy among those underwent adenoidectomy. One hundred and thirty patients were enrolled. The MAGS showed high inter-rater reliability with a Kappa score of 0.869. Sixty of 130 patients underwent adenoidectomy and assessed with intraoperative nasal endoscopy. The MAGS significantly correlated to the percentage of nasopharyngeal obstruction of intraoperative endoscopy (Spearman's r = 0.796, gamma coefficient = 0.94), and the percentage of choanal obstruction of preoperative endoscopy (Spearman's r = 0.816, gamma coefficient = 0.859). Our findings suggest that the MAGS has high reliability and validity for assessment of adenoid size. It may be a more suitable and reliable grading system for endoscopic evaluation of adenoid size.

Chinese expert recommendation on transnasal corticosteroid nebulization for the treatment of chronic rhinosinusitis 2021.

Corticosteroids are efficacious in treating chronic rhinosinusitis (CRS), but concerns on the potential side effects remain, especially for long-term usage of systemic corticosteroids. Accumulated evidence shows that transnasal nebulization may be a reasonable solution in balancing both efficacy and safety. However, no consensus or guideline has been formulated on the use of steroid transnasal nebulization in treating CRS. The consensus is achieved through literature review and exchange of Chinese experts in Group of Otorhinolaryngology and Ophthalmology, Chinese Society of Allergy (CSA). This document covers the development, equipment, pharmacological mechanism, and evidence-based efficacy and safety, as well as the special concern of the application of steroid transnasal nebulization during the coronavirus disease (COVID-19) pandemic. The expert consensus clarifies the application of steroid transnasal nebulization in treating CRS and common comorbidities during the perioperative and postoperative periods.

Elevated Levels of Activated and Pathogenic Eosinophils Characterize Moderate-Severe House Dust Mite Allergic Rhinitis.

Eosinophils play a critical role in the pathogenesis of allergic airway inflammation. However, the relative importance of eosinophil activation and pathogenicity in driving the progression of disease severity of allergic rhinitis (AR) remains to be defined. We aimed to assess the relation of activated and pathogenic eosinophils with disease severity of patients with AR. Peripheral blood and nasal samples were collected from patients with mild (n = 10) and moderate-severe (n = 21) house dust mite AR and healthy control subjects (n = 10) recruited prospectively. Expressions of activation and pathogenic markers on eosinophils in the blood and nose were analyzed by flow cytometry. The eosinophilic cation protein- (ECP-) releasing potential and the pro-Th2 function of blood eosinophils were compared between the mild and moderate-severe patients and healthy controls. Our results showed that the numbers of activated (CD44+ and CD69+) and pathogenic (CD101+CD274+) eosinophils in the blood and nose as well as blood eosinophil progenitors were increased in moderate-severe AR compared with the mild patients and healthy controls. In addition, the levels of activated and pathogenic eosinophils in the blood were positively correlated with the total nasal symptom score and serum ECP and eosinophil peroxidase (EPX) levels in patients with AR. Furthermore, the blood eosinophils obtained from the moderate-severe patients exhibited a higher potential of releasing ECP and EPX induced by CCL11 and of promoting Th2 responses than those from the mild patients and healthy controls. In conclusion, patients with moderate-severe AR are characterized by elevated levels of activated and pathogenic eosinophils, which are associated with higher production of ECP, EPX, and IL-4 in the peripheral blood.

Combinatorial IL-17RB, ST2, and TSLPR Signaling in Dendritic Cells of Patients With Allergic Rhinitis.

OBJECTIVES: Myeloid dendritic cells (DCs) in patients with allergic rhinitis (AR) express higher levels of IL-17RB, ST2, and TSLPR. However, their functional roles in DCs are much less clear. This study aimed to determine the combined effects of these three receptor signals on the T cell-polarizing function of DCs in AR patients. METHODS: Monocyte-derived DCs (mo-DCs) were generated and stimulated with Toll-like receptor (TLR) 1-9 ligands. Der.p1-induced mo-DCs were stimulated with different combinations of IL-25, IL-33, and TSLP to determine phenotypic characteristics and then co-cultured with CD4+ T cells to assess Th2 cytokine production. Expression levels of IL-17RB, ST2, and TSLPR on myeloid DCs (mDCs) from peripheral blood of AR and healthy subjects were detected to confirm the association of these receptors with disease severity. RESULTS: TLR ligands induced AR-derived mo-DCs to increase IL-17RB, ST2, and TSLPR expression by varying degrees; among these, Der.p1 was the strongest inducer. Der.p1-induced mo-DCs from AR showed increased OX40L expression. IL-25, IL-33, and TSLP (alone or in double combination) significantly increased OX40L expression on Der.p1-induced mo-DCs from AR, thereby increasing the production of IL-4, IL-5, and IL-13 in co-cultured CD4+ T cells; triple combination further enhanced these effects. The percentage of IL-17RB+ST2+TSLPR+ mDCs was increased in AR, higher in moderate to severe phase than in mild phase, and positively correlated with the percentages of IL-4+, IL-5+, and IL-13+ T cells. CONCLUSION: A combination of IL-17RB, ST2, and TSLPR signals amplified the Th2-polarizing function of DCs and was associated with disease severity in AR patients.

USP22 controls iNKT immunity through MED1 suppression of histone H2A monoubiquitination.

The ubiquitin pathway has been shown to regulate iNKT cell immunity, but the deubiquitinase involved in this process has not been identified. Herein we found that ubiquitin-specific peptidase 22 (USP22) is highly expressed in iNKT cells during their early developmental stage 1. USP22 deficiency blocked the transition from stage 1 to 2 during iNKT cell development in a cell-intrinsic manner. USP22 suppression also diminishes iNKT17 and iNKT1 differentiation but favors iNKT2 polarization without altering conventional T cell activation and differentiation. USP22 interacts with the Mediator complex subunit 1 (MED1), a transcription coactivator involved in iNKT cell development. Interestingly, while interacting with MED1, USP22 does not function as a deubiquitinase to suppress MED1 ubiquitination for its stabilization. Instead, USP22 enhances MED1 functions for IL-2Rß and T-bet gene expression through deubiquitinating histone H2A but not H2B monoubiquitination. Therefore, our study revealed USP22-mediated histone H2A deubiquitination fine-tunes MED1 transcriptional activation as a previously unappreciated molecular mechanism to control iNKT development and functions.