Efficacy of repetitive transcranial magnetic stimulation in post-stroke cognitive impairment: an overview of systematic reviews.

Objective: The reliability of clinical evidence depends on high-quality meta-analyses/ systematic reviews (MAs/SRs). However, there has been no assessment of the quality of MAs/SRs for repetitive transcranial magnetic stimulation (rTMS) in post-stroke cognitive impairment (PSCI), both nationally and internationally. This article seeks to use radar plotting to visually present the quality of MAs/SRs on rTMS for improving cognitive function in PSCI, aiming to offer an intuitive foundation for clinical research. Methods: Eight Chinese or English databases were systematically searched to collect comprehensive literature, and the retrieval time ranged from inception to 26 March 2024. Literature ranking was calculated using six dimensions: publication year, design type, AMSTAR-2 score, PRISMA score, publication bias, and homogeneity. Finally, radar plots were drafted to present a multivariate literature evaluation. The GRADE tool assessed the strength of evidence for the outcome indicators included in the MAs/SRs. Results: The 17 articles included had average scores of 12.29, 17, 9.88, 9.71, 12.88, and 12.76 for each dimension. The radar plot showed that an article published in 2023 had the highest rank and a large radar plot area, while an article published in 2021 had the lowest rank and a small radar plot area. The GRADE tool evaluation revealed that 51 pieces of evidence were of very low quality, 67 were of low quality, 12 were of moderate quality, and only one was of high quality. Conclusion: The average rank score of literature ranged from 8.50 to 17, with higher rankings indicating greater significance in literature reference. Variations in literature quality were attributed to inadequate study planning, irregular literature search and screening, insufficient description of inclusion criteria for studies, and inadequate consideration of bias risk in the included studies. Most MAs/SRs indicated that rTMS was more effective than the control group in enhancing the global cognitive function and activities of daily living in PSCI patients. However, the overall quality of the literature was generally low and needs validation from future high-quality evidence.Systematic review registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42023491280.

The diagnostic value of image-enhanced endoscopy system in sinonasal inverted papilloma.

PURPOSE: This study aimed to evaluate the diagnostic value of image-enhanced endoscopy (IEE) in detecting sinonasal inverted papilloma (SNIP). METHODS: Overall, 86 patients with unilateral nasal papillary or lobulated neoplasms were included between July 2018 and June 2019. All patients underwent IEE examinations, and the diagnosis of all neoplasms was confirmed through postoperative pathology. Logistic regression analysis was conducted to screen for independent predictors of various types of vascular patterns of SNIP. Furthermore, a prognostic nomogram was constructed using the independent predictors screened by logistic regression analysis to evaluate its usefulness in distinguishing SNIP from nasal polyp (NP) and papillary mucosa folds (PMF). RESULTS: In total, 86 consecutive cases were observed, including 37 with SNIP, 40 with NP, and 9 with PMF. Logistic regression analysis showed that spot, corkscrew, and multilayered vascular patterns were independent predictors of SNIP diagnosis. Furthermore, a nomogram comprising the three independent risk factors was constructed with scores of 5, 2, and 3. The area under the receiver operating characteristic curve for predicting SNIP was 0.954, 0.66, 0.71, and 0.76 for the nomogram model, spot vascular pattern, corkscrew vascular pattern, and multilayered vascular pattern, respectively. CONCLUSION: The nomogram model based on spot, corkscrew, and multilayered vascular patterns in SNIP observed using IEE can be a useful diagnostic tool for predicting and distinguishing between NP and PMF.

Comparison of clinical traits for seasonal and perennial allergic rhinitis during allergen exposure.

Background: Allergic rhinitis (AR) is traditionally subdivided into seasonal AR (SAR) and perennial AR (PAR) according to the type of allergen and the occurrence of symptoms during the year. There are currently no reports on the comparison of trait profiles for SAR and PAR during the allergen exposure. Purpose: The purpose of this study was to analyze the clinical characteristics of SAR and PAR during respective allergen exposure periods to provide valuable information for the development of treatment strategies. Methods: This study was performed between August 1, 2021, and January 31, 2022, in the Department of Allergy, Beijing Tongren Hospital. We continuously included diagnosed SAR and PAR outpatients who volunteered to participate in the survey. A questionnaire with regard to medical history, severity of symptoms, and diagnosis and treatment status was collected. Results: A total of 296 patients with SAR and 448 with PAR were finally recruited. Patients with SAR had more severe rhinorrhea compared with patients with PAR (p < 0.001), whereas there was no statistically significant difference in the severity of itching, sneezing, and congestion between the two entities (p ≥ 0.05). Both the gritty and watery eyes of patients with SAR were noticeably more severe than those of patients with PAR (PTotal Ocular Symptom Score [PTOSS] < 0.001). AR symptom severity is mainly associated with the comorbid allergic conjunctivitis (odds ratio 1.94 [95% confidence interval, 1.21-3.09]). SAR patients and PAR patients show no statistically significant differences in terms of their frequency of visits, annual expenditure, and choice of medication treatment for AR (p > 0.05). The overall control under standard medication of both patients with PAR and those with SAR is not ideal, especially in SAR. Conclusion: The current cross-sectional study demonstrated that the patients with SAR exhibited more severe overall clinical symptoms than those with PAR, especially nasal rhinorrhea and gritty and watery eyes. Both of the two disease entities have poor control under standardized medication treatment, especially in SAR. Further multicenter longitudinal studies that involve larger and more diverse populations should be conducted to provide a more accurate and comprehensive understanding of the condition.

First-In-Human Study on Pharmacokinetics, Safety, and Tolerability of Single and Multiple Escalating Doses of PA9159 Nasal Spray, a Highly Potent Glucocorticoid in Healthy Chinese Volunteers.

OBJECTIVE: PA9159 (previously named VSG159) is a structurally novel and highly potent glucocorticoid that plays a role in the late development of autoimmune and inflammatory diseases. The current first-in-human ascending-dose study of the PA9159 nasal spray was conducted in healthy Chinese volunteers to evaluate its pharmacokinetics, safety, and tolerability. In addition, the effects of PA9159 on serum cortisol secretion were investigated. METHODS: This was a double-blinded, randomized, placebo-controlled clinical study that included four single-dose groups in the single ascending dose cohort (SAD) and two multiple-dose groups in the multiple ascending dose cohort (MAD), with dose ranges of 10-80 µg and 20-40 µg, respectively. PA9159 was administered bilaterally via nasal spray once only or once daily for seven days. Pharmacokinetic, safety, and tolerability profiles were evaluated. RESULTS: A total of 60 participants completed the study. PA9159 doses of up to 80 µg in the SAD and up to 40 µg in the MAD were shown to be safe and tolerable. The most common treatment-related AEs were mild and transient local nasal AEs. Morning serum cortisol levels approximately remained unchanged in both the single-dose and multiple-dose groups. PA9159 was quantified in 41.8% (368/880) of the samples in all treatment groups, including 25.2% (105/416) of the SAD and 56.7% (263/464) of the MAD. The majority (>80.0%) of PA9159 plasma concentrations ranged from 0.5 to 2 pg/mL in determined samples. The mean AUC0-t of PA9159 in the SAD was 0.91, 1.39±0.68, 11.40±9.91, and 46.30±25.80 h*pg/mL in the 10 to 80 ug single group. The mean terminal half-life time (t1/2) was 8.43 h and 8.97±2.28 h in 40 ug and 80 ug single group, respectively. The mean AUCss of PA9159 in the MAD was 31.70±7.04, 44.20±20.60 h*pg /mL, and the t1/2 was 16.00±4.18 h, 21.20±10.20 h in the 20 ug and 40 ug multiple groups, respectively. The median Tmax was approximately 6 hours in both the SAD and MAD cohorts. CONCLUSIONS: The PA9159 nasal spray was generally safe and well tolerated, and the effects of PA9159 on serum cortisol levels were limited. The plasma concentration and systemic exposure to PA9159 were very low. These findings support the necessity for further clinical studies on PA9159 nasal spray in patients suffering from allergic rhinitis.

SerpinB3/B4 Abates Epithelial Cell-Derived CXCL8/IL-8 Expression in Chronic Rhinosinusitis with Nasal Polyps.

Background: Serine proteinase inhibitors, clade B, member 3 (SerpinB3) and B4 are highly similar in amino acid sequences and associated with inflammation regulation. We investigated SerpinB3 and B4 expression and their roles in chronic rhinosinusitis with nasal polyps (CRSwNP). Methods: The expression of SerpinB3 and B4 in nasal mucosa tissues, brush cells, and secretions from CRSwNP patients was measured, and their regulation by inflammatory cytokines were investigated. Their functions were also analyzed using air-liquid interface (ALI)-cultured primary human nasal epithelial cells (HNECs) and transcriptomic analysis. Results: Both SerpinB3 and B4 expression was higher in nasal mucosa, brush cells, and secretions from eosinophilic (E) CRSwNP and nonECRSwNP patients than in healthy controls. Immunofluorescence staining indicated that SerpinB3 and B4 were primarily expressed in epithelial cells and their expression was higher in CRSwNP patients. SerpinB3 and B4 expression was upregulated by interleukin-4 (IL-4), IL-5, IL-6, and IL-17a. Transcriptomic analysis identified differentially expressed genes (DEGs) in response to recombinant SerpinB3 and B4 stimulation. Both the DEGs of SerpinB3 and B4 were associated with disease genes of nasal polyps and inflammation in DisGeNET database. Pathway enrichment indicated that downregulated DEGs of SerpinB3 and B4 were both enriched in cytokine-cytokine receptor interactions, with CXCL8 as the hub gene in the protein-protein interaction networks. Furthermore, CXCL8/IL-8 expression was downregulated by recombinant SerpinB3 and B4 protein in ALI-cultured HNECs, and upregulated when knockdown of SerpinB3/B4. Conclusion: SerpinB3/B4 expression is upregulated in nasal mucosa of CRSwNP patients. SerpinB3/B4 may play an anti-inflammatory role in CRSwNP by inhibiting the expression of epithelial cell-derived CXCL8/IL-8.

Comparative efficacy of different repetitive transcranial magnetic stimulation protocols for lower extremity motor function in stroke patients: a network meta-analysis.

Background: Lower extremity motor dysfunction is one of the most severe consequences after stroke, restricting functional mobility and impairing daily activities. Growing evidence suggests that repetitive transcranial magnetic stimulation (rTMS) can improve stroke patients' lower extremity motor function. However, there is still controversy about the optimal rTMS protocol. Therefore, we compared and analyzed the effects of different rTMS protocols on lower extremity motor function in stroke patients using network meta-analysis (NMA). Methods: We systematically searched CNKI, WanFang, VIP, CBM, PubMed, Embase, Web of Science, and Cochrane Library databases (from origin to 31 December 2023). Randomized controlled trials (RCTs) or crossover RCTs on rTMS improving lower extremity motor function in stroke patients were included. Two authors independently completed article screening, data extraction, and quality assessment. RevMan (version 5.4) and Stata (version 17.0) were used to analyze the data. Results: A total of 38 studies with 2,022 patients were eligible for the NMA. The interventions included HFrTMS-M1, LFrTMS-M1, iTBS-Cerebellum, iTBS-M1, dTMS-M1, and Placebo. The results of NMA showed that LFrTMS-M1 ranked first in FMA-LE and speed, and HFrTMS-M1 ranked first in BBS, TUGT, and MEP amplitude. The subgroup analysis of FMA-LE showed that HFrTMS-M1 was the best stimulation protocol for post-stroke time > 1 month, and LFrTMS-M1 was the best stimulation protocol for post-stroke time ≤ 1 month. Conclusion: Considering the impact of the stroke phase on the lower extremity motor function, the current research evidence shows that HFrTMS-M1 may be the preferred stimulation protocol to improve the lower extremity motor function of patients for post-stroke time > 1 month, and LFrTMS-M1 for post-stroke time ≤ 1 month. However, the above conclusion needs further analysis and validation by more high-quality RCTs.Systematic Review Registration:www.crd.york.ac.uk/prospero/, identifier (CRD42023474215).

Anti-thymic stromal lymphopoietin monoclonal antibody in patients with chronic rhinosinusitis with nasal polyps (DUBHE): Rationale and design of a multicenter, randomized, double-blind, placebo-controlled study.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) has a complex pathogenesis and is difficult to treat, which brings a huge economic burden to society. Despite all the progress in the treatment of CRSwNP, some patients with CRSwNP still experience recurrence. Therefore, there is an urgent need to develop novel drugs and treatments for CRSwNP. Thymic stromal lymphopoietin (TSLP) is produced by epithelial cells and mediates type 2 and nontype 2 inflammation through various downstream cellular immune and inflammatory pathways. Anti-TSLP treatment with tezepelumab has been proven to be effective in treating patients with uncontrolled asthma, regardless of their peripheral blood eosinophil levels being low or high. However, there is no relevant research on the usage of anti-TSLP monoclonal antibodies for the treatment of uncontrolled CRSwNP. Objective: This is the first phase Ib/IIa study for subjects with uncontrolled CRSwNP, aiming to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary efficacy of multiple ascending doses (MAD) of anti-TSLP monoclonal antibody. Methods: The DUBHE is a multicenter, randomized, double-blind, placebo-controlled, phase Ib/IIa clinical study. The study will be composed of 3 periods: a screening/run-in period of 4 weeks, a treatment period of 52 weeks (16 weeks of double-blind treatment period +36 weeks of open-label treatment period), and a safety follow-up period of 12 weeks. No more than 113 subjects with uncontrolled CRSwNP will be divided into 4 groups to receive different doses of CM326 or placebo treatments (55 mg every two weeks [Q2W] group, 110 mg Q2W group, 220 mg Q2W group, and 220 mg every four weeks [Q4W] group). Enrolled patients will be stratified by tissue eosinophil count (TEC). Results: The safety of the monoclonal antibody that targets TSLP in uncontrolled CRSwNP and its preliminary efficacy at 16 weeks of treatment. Conclusion: In this study, for the first time, the safety and preliminary efficacy of MAD of CM326 will be verified. The efficacy of CM326 in patients with eosinophilic CRSwNP (TEC ≥55/high power field [HPF]), as well as noneosinophilic CRSwNP (TEC <55/HPF) will be testified. Trial registration: NCT05324137.

Efficacy and safety of stapokibart (CM310) in uncontrolled seasonal allergic rhinitis (MERAK): an investigator-initiated, placebo-controlled, randomised, double-blind, phase 2 trial.

Background: There is no trial to assess the benefits of periodically using biologics during the pollen season in patients with uncontrolled seasonal allergic rhinitis (SAR), who have moderate-to-severe symptoms even after standard-of-care. This trial aimed to evaluate the efficacy and safety of the add-on administration of stapokibart, a humanised monoclonal antibody that targets interleukin-4 receptor alpha, in patients with uncontrolled SAR. Methods: In this investigator-initiated, randomised, double-blind, placebo-controlled trial, eligible patients received either stapokibart 600-300 mg weekly (QW), every 2 weeks (Q2W), or placebo QW for 4 weeks. All patients were given mometasone furoate nasal spray and loratadine throughout the trial. The primary endpoint was the mean change from baseline in daily reflective total nasal symptom score (rTNSS) during 2-week treatment. Secondary efficacy outcomes included: the mean change from baseline in daily rTNSS during 4-week treatment; the mean changes and the mean percentage changes from baseline during 2-week and 4-week treatment in 1) daily rTNSS and reflective total ocular symptom score (rTOSS), 2) morning (AM)/evening (PM) rTNSS and rTOSS, 3) AM instantaneous total nasal symptom score (iTNSS) and instantaneous total ocular symptom score (iTOSS), 4) individual nasal and ocular symptoms; the change from baseline in Rhinoconjunctivitis Quality of-Life Questionnaire score during 4-week treatment. Exploratory endpoints included the change of prespecified markers related to type 2 inflammation pre- and post-treatment. Safety, immunogenicity, and pharmacokinetics were also evaluated. This study is registered with www.clinicaltrials.gov (NCT05470647). Findings: Between August 17, 2022, and December 28, 2022, 92 patients with uncontrolled SAR were enrolled from 4 centres in China and randomly assigned to receive stapokibart 600-300 mg QW (n = 31), stapokibart 600-300 mg Q2W (n = 30), or placebo QW (n = 31), of whom 86 (93%) completed the study. Both stapokibart Q2W and QW did not significantly improve mean change from baseline in daily rTNSS compared with placebo in 2 weeks. The least-squares (LS) mean differences (97.5% confidence interval [CI]) compared with placebo were -1.0 (-2.3, 0.2) in stapokibart Q2W group (p = 0.065) and -0.2 (-1.5, 1.0) in stapokibart QW group (p = 0.67). For the secondary outcomes, compared with placebo, stapokibart Q2W presented significant improvements in the mean percentage change from baseline in daily rTNSS in 2 weeks (LS mean difference -12.9%, 95% CI -25.3%, -0.4%, p = 0.043), as well as AM iTNSS over 2 weeks (LS mean difference -17.4%, 95% CI -31.0%, -3.8%, p = 0.013) and 4 weeks (LS mean difference -15.4%, 95% CI -29.0%, -1.9%, p = 0.026). Additionally, the nasal congestion score was significantly lower in stapokibart Q2W than placebo during 2-week (LS mean difference -0.4, 95% CI -0.7, -0.1, p = 0.014) and 4-week (LS mean difference -0.4, 95% CI -0.7, -0.04, p = 0.028) treatment. Treatment-emergent adverse events (TEAEs) occurred in 48% (15/31), 33% (10/30), and 61% (19/31) of patients receiving stapokibart QW, Q2W, and placebo, respectively. Most reported TEAEs were sinus bradycardia, hyperlipidaemia, and blood uric acid increased. Interpretation: In this phase 2 trial, both stapokibart regimens had an acceptable safety and tolerability profile but did not significantly improve daily rTNSS in patients with uncontrolled SAR. The efficacy of stapokibart in patients with uncontrolled SAR is being further investigated in ongoing phase 3 trials (clinicaltrials.gov, NCT05908032). Funding: Ministry of Science and Technology of the People's Republic of China; Ministry of Education of the People's Republic of China; National Natural Science Foundation of China; Chinese Academy of Medical Sciences.

Expert consensus on odontogenic maxillary sinusitis multi-disciplinary treatment.

ABSTARCT: Odontogenic maxillary sinusitis (OMS) is a subtype of maxillary sinusitis (MS). It is actually inflammation of the maxillary sinus that secondary to adjacent infectious maxillary dental lesion. Due to the lack of unique clinical features, OMS is difficult to distinguish from other types of rhinosinusitis. Besides, the characteristic infectious pathogeny of OMS makes it is resistant to conventional therapies of rhinosinusitis. Its current diagnosis and treatment are thus facing great difficulties. The multi-disciplinary cooperation between otolaryngologists and dentists is absolutely urgent to settle these questions and to acquire standardized diagnostic and treatment regimen for OMS. However, this disease has actually received little attention and has been underrepresented by relatively low publication volume and quality. Based on systematically reviewed literature and practical experiences of expert members, our consensus focuses on characteristics, symptoms, classification and diagnosis of OMS, and further put forward multi-disciplinary treatment decisions for OMS, as well as the common treatment complications and relative managements. This consensus aims to increase attention to OMS, and optimize the clinical diagnosis and decision-making of OMS, which finally provides evidence-based options for OMS clinical management.

Comparative efficacy of different exercise methods to improve cardiopulmonary function in stroke patients: a network meta-analysis of randomized controlled trials.

Background: Although some studies have shown that exercise has a good effect on improving the cardiopulmonary function of stroke patients, it still needs to be determined which exercise method does this more effectively. We, therefore, aimed to evaluate the effectiveness of different exercise methods in improving cardiovascular function in stroke patients through a network meta-analysis (NMA), providing a basis to select the best treatment plan for stroke patients. Methods: We systematically searched CNKI, WanFang, VIP, CBM, PubMed, Embase, Web of Science, and The Cochrane Library databases from establishment to 30 April 2023. Randomized controlled trials (RCTS) on exercise improving cardiopulmonary function in stroke patients were included, and we screened the included articles and extracted the relevant data. RevMan (version 5.4) and Stata (version 17.0) were used for data analysis. Results: We included 35 RCTs and a total of 2,008 subjects. Intervention measures included high-intensity interval training (HIIT), aerobic training (AT), resistance training (RT), combined aerobic and resistance exercise (CE), and conventional therapy (CT). In the network meta-analysis, the surface under the cumulative ranking area (SUCRA) ranking result indicated that HIIT improved peak oxygen uptake (VO2peak) and 6 mins walking distance (6MWD) optimally, with rankings of HIIT (100.0%) > CE (70.5%) > AT (50.2%) > RT (27.7%) > CT (1.6%), and HIIT (90.9%) > RT (60.6%) > AT (48.9%) > RT (48.1%) > CT (1.5%), respectively. The SUCRA ranking result showed that CE improved systolic blood pressure (SBP) and diastolic blood pressure (DBP) optimally, with rankings of CE (82.1%) > HIIT (49.8%) > AT (35.3%) > CT (32.8%), and CE (86.7%) > AT (45.0%) > HIIT (39.5%) > CT (28.8%), respectively. Conclusion: We showed that exercise can effectively improve the cardiopulmonary function of stroke patients. HIIT was the most effective in improving VO2peak and 6MWD in stroke patients. CE was the most effective in improving SBP and DBP in stroke patients. However, due to the limitations of existing clinical studies and evidence, larger sample size, multi-center, and high-quality RCTs are needed to verify the above conclusions in the future. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier [CRD42023436773].

Matrix metalloproteinases in chronic rhinosinusitis.

INTRODUCTION: Matrix metalloproteinases (MMPs) are a group of enzymes that are essential in maintaining extracellular matrix (ECM) homeostasis, regulating inflammation and tissue remodeling. In chronic rhinosinusitis (CRS), the overexpression of certain MMPs can contribute to chronic nasal tissue inflammation, ECM remodeling, and tissue repair. AREAS COVERED: This review provides a comprehensive overview of the biological characteristics and functions of the MMP family, particularly focusing on the expression and activity of MMPs in patients with CRS, and delves into their role in the pathogenesis of CRS and their potential as therapeutic targets. EXPERT OPINION: MMPs are important in tissue remodeling and have been implicated in the pathophysiology of CRS. Previous studies have shown that the expression of MMPs is upregulated in the nasal mucosa of patients with CRS and positively correlates with the severity of CRS. However, there is still a large gap in the research content of MMP in CRS, and the specific expression and pathogenic mechanism of MMP still need to be clarified. The significance and value of the ratio of MMP to tissue inhibitors of metalloproteinase (TIMP) in diseases still need to be demonstrated. Moreover, further studies are needed to assess the efficacy and safety of biologics that target MMPs in patients with CRS.

The mucosal concept in chronic rhinosinusitis: Focus on the epithelial barrier.

Chronic rhinosinusitis (CRS) is a common chronic nasal cavity and sinus disease affecting a growing number of individuals worldwide. Recent advances have shifted our understanding of CRS pathophysiology from a physical obstruction model of ventilation and drainage to a mucosal concept that recognizes the complexities of mucosal immunologic variations and cellular aberrations. A growing number of studies have demonstrated the alteration of the epithelial barrier during inflammatory states. Therefore, the current review has focused on the crucial role of epithelial cells within this mucosal framework in CRS, detailing the perturbed epithelial homeostasis, impaired epithelial cell barrier, dysregulated epithelial cell repair processes, and enhanced interactions between epithelial cells and immune cells. Notably, the utilization of novel technologies, such as single-cell transcriptomics, has revealed the novel functions of epithelial barriers, such as inflammatory memory and neuroendocrine functions. Therefore, this review also emphasizes the importance of epithelial inflammatory memory and the necessity of further investigations into neuroendocrine epithelial cells and neurogenic inflammation in CRS. We conclude by contemplating the prospective benefits of epithelial cell-oriented biological treatments, which are currently under investigation in rigorous randomized, double-blind clinical trials in patients with CRS with nasal polyps.

IgE directly affects eosinophil migration in chronic rhinosinusitis with nasal polyps through CCR3 and predicts the efficacy of omalizumab.

BACKGROUND: Whether IgE affects eosinophil migration in chronic rhinosinusitis with nasal polyps (CRSwNP) remains largely unclear. Moreover, our understanding of local IgE, eosinophils, and omalizumab efficacy in CRSwNP remains limited. OBJECTIVE: We investigated whether IgE acts directly on eosinophils and determined its role in omalizumab therapy. METHODS: Eosinophils and their surface receptors were detected by hematoxylin and eosin staining and flow cytometry. IgE and its receptors, eosinophil peroxidase (EPX), eosinophilic cationic protein, and CCR3 were detected by immunohistochemistry and immunofluorescence. Functional analyses were performed on blood eosinophils and polyp tissues. Logistic regression was performed to screen for risk factors. Receiver operating characteristic curve was generated to evaluate the accuracy. RESULTS: Both FcεRI and CD23 were expressed on eosinophils. The expression of FcεRI and CD23 on eosinophil in nasal polyp tissue was higher than in peripheral blood (both P < .001). IgE and EPX colocalized in CRSwNP. IgE directly promoted eosinophil migration by upregulating CCR3 in CRSwNP but not in healthy controls. Omalizumab and lumiliximab were found to be effective in restraining this migration, indicating CD23 was involved in IgE-induced eosinophil migration. Both IgE+ and EPX+ cells were significantly reduced after omalizumab treatment in those who experienced response (IgE+ cells, P = .001; EPX+ cells, P = .016) but not in those with no response (IgE+ cells, P = .060; EPX+ cells, P = .151). Baseline IgE+ cell levels were higher in those with response compared to those without response (P = .024). The baseline local IgE+ cell count predicted omalizumab efficacy with an accuracy of 0.811. CONCLUSIONS: IgE directly promotes eosinophil migration, and baseline local IgE+ cell counts are predictive of omalizumab efficacy in CRSwNP.

Induction of a type 2 inflammatory chronic rhinosinusitis in C57BL/6 mice.

Background: Eosinophilic chronic rhinosinusitis (CRS) has been widely studied for its intractability and high recurrence rate. It can be divided into pure and mixed type 2 CRS subtypes. Mouse models that reflect pure type 2 inflammation of CRS are lacking. Objective: This study aims to establish a relatively pure type 2 CRS mouse model and compare it with 2 mixed type 2 CRS models. Methods: Three mouse CRS models were constructed: (1) aerosol ovalbumin (OVA) + aspergillus oryzae-derived protease (AP); (2) intranasal OVA + AP; (3) Intraperitoneal then intranasal OVA + AP (n = 10 per group). Nasal, lung symptoms, IgE, inflammatory cells, cytokines, and remodeling factors were evaluated. Results: Histological and micro-computed tomography showed inflammation, polyps, and opacification in all 3 experimental groups. The aerosol group had significantly increased local eosinophils and type 2 cytokines, while other types of cytokines showed no noticeable change. The nasal instillation groups also showed elevated other inflammatory factors and tissue polypoid changes were more pronounced. More severe pulmonary inflammation was observed with aerosol delivery. Conclusion: Aerosol inhalation mouse model is superior for studying nasal relatively pure type 2 inflammation and lower airway comorbidities.

The Efficacy of Budesonide, Levocabastine, and Their Combination in Treatment of Vasomotor Rhinitis.

INTRODUCTION: Relevant studies have demonstrated that glucocorticoids and antihistamines, such as budesonide and azelastine, are effective in the treatment of vasomotor rhinitis, with their combined use being more effective than that of a single drug. The aim of this study was to assess the improvement in the symptoms of patients following the combined administration of these drugs. METHODS: We conducted a single-center randomized study on 42 patients. Participants were randomly treated with budesonide, levocabastine hydrochloride, or their combination for 2 weeks. The visual analog scale (VAS) score and levels of eosinophil cationic protein (ECP), histamine (HA), leukotriene B4 (LTB4), and vasoactive intestinal peptide (VIP) in nasal secretions were evaluated before and after treatment. RESULTS: The symptoms of patients were improved in all 3 treatment groups compared with those before treatment. Following combined treatment, the improvement in symptoms of nasal obstruction, runny nose, nasal itching, and sneezing was much greater than those in the groups treated with budesonide or levocabastine hydrochloride alone (p = 0.04, 0.004, 0.005, 0.004, respectively). The decreased levels of these inflammatory mediators were significantly different between the different treatment groups. CONCLUSIONS: Budesonide or levocabastine hydrochloride alone improved the nasal symptoms of patients with vasomotor rhinitis and reduced the levels of ECP, HA, LTB4, and VIP in nasal secretions. However, their combination improved the symptoms of patients more significantly than each drug alone.

[Differential expression of NEDD8 in different pathological types of chronic rhinosinusitis with nasal polyps].

Objective:To analyze the differential expression of neural precursor cell-expressed developmentally downregulated 8（NEDD8） protein in nasal polyp tissues of patients with different pathological types of chronic rhinorhinosinusitis with nasal polyps（CRSwNP）. Methods:All specimens were obtained from the specimen library of Beijing Tongren Hospital, and were all patients who underwent nasal endoscopic surgery for chronic rhinosinusitis in Beijing Tongren Hospital. Hematoxylin-eosin staining（HE） was used to detect the number of eosinophils in nasal polyps, and CRSwNP patients were grouped according to the number of eosinophils in nasal polyps, immunohistochemistry was used to detect and analyze the expression level of NEDD8 protein in nasal polyps. Results:The expression level of NEDD8 protein in nasal polyps of patients with eosinophilic chronic rhinorhinosinusitis with nasal polyps was significantly higher than that of patients with non-eosinophilic chronic rhinosinusitis and nasal polyps（P<0.05）. In addition, there was a significant positive correlation between the expression level of NEDD8 protein and the number of eosinophils in nasal polyp tissue（r=0.79, P=0.02）. Conclusion:There are differences in the expression of NEDD8 protein in patients with chronic rhinosinusitis and nasal polyps of different pathological types.

Current and emerging biological therapies for Chronic rhinosinusitis with nasal polyps with type 2 inflammation.

INTRODUCTION: Chronic rhinosinusitis with nasal polyps (CRSwNP), especially CRSwNP with type 2 inflammation, remains the most difficult-to-treat subtype with high prevalence worldwide. The emergence of biologics has the potential to fulfill the unmet medical needs of patients with CRSwNP driven by type 2 inflammation. AREAS COVERED: A current review of the literature was performed to overview current and emerging biological therapies in the treatment of CRSwNP. EXPERT OPINION: In an era of precision medicine, biologics have been given expectations to provide customized therapies to patients with CRSwNP, particularly those with refractory CRSwNP. Large clinical trials and real-world experiences are both essential for the application of biologics. Moreover, to make biological therapy more tailored to patients, an in-depth understanding of the different mechanisms of biologics, further elucidating the relationship between biologics and conventional medical and surgical treatments, and identifying predictive biomarkers warrant thorough investigations.