[Expert consensus on the diagnosis and treatment of respiratory diseases exacerbated by nonsteroidal anti-inflammatory drugs （2024, Chengdu）].

Non-steroidal anti-inflammatory drugs-exacerbated respiratory disease （N-ERD） is a chronic respiratory disease characterized by eosinophilic inflammation, featuring chronic rhinosinusitis （CRS）, asthma, and intolerance to cyclooxygenase 1 （COX-1） inhibitors. The use of these medications can lead to an acute worsening of rhinitis and asthma symptoms. This condition has not yet received sufficient attention in China, with a high rate of misdiagnosis and a lack of related research. The Chinese Rhinology Research Group convened a group of leading young experts in otolaryngology from across the country, based on the latest domestic and international evidence-based medical practices to formulate this consensus.The consensus covers the epidemiology, pathogenesis, clinical manifestations, diagnostic methods, and treatment strategies for N-ERD, including pharmacotherapy, surgery, biologic treatments, and desensitization therapy. The goal is to improve recognition of N-ERD, reduce misdiagnosis, and enhance treatment outcomes.

Association between depression and tinnitus in US adults: A nationally representative sample.

Background: Data from the National Health and Nutrition Examination Survey (NHANES) has not been previously utilized to study the prevalence of tinnitus and depression among adults over 20 years old, nor the impact of tinnitus on depression. Objective: The aim of this study was to evaluate the relationship between tinnitus and depression among adults in the United States. Materials and Methods: This cross-sectional study drew upon data from the 2005-2018 NHANES, incorporating adults aged 20 and older who had completed the tinnitus and depression questionnaire. Depression was assessed using the PHQ-9 questionnaire. Multivariate logistic regression models, subgroup analyses, and sensitivity analyses were performed to examine the association between tinnitus and depression. Results: This nationally representative study included 10,409 participants, of whom 17.69% reported experiencing tinnitus. The prevalence of depression was 6.2% among those without tinnitus and 15.1% among those with tinnitus (p < .0001). Accounting for potential confounders such as demographic and socioeconomic variables, participants who experienced tinnitus were more likely to exhibit depression symptoms (adjusted odds ratio = 2.0, 95% confidence interval = 1.61-2.48). Subgroup analyses further suggested that tinnitus was associated with an increased prevalence of depression across all subgroups. Sensitivity analysis affirmed these findings. Conclusions: This study suggests that there is a significant association between tinnitus and the risk of depression in the adult population of the United States, emphasizing the importance of psychological factors in the clinical management of tinnitus. Level of Evidence: 2b.

The Age-Related Growth of Mastoid Air Cells in Infancy: A Retrospective Cross-Sectional Study.

OBJECTIVES: To investigate the normal growth and development of mastoid pneumatization volume from 5 to 12 months for pediatric otosurgeons. STUDY DESIGN: Retrospective chart review. SETTING: A tertiary referral center. PATIENTS: This study evaluated age-dependent changes in mastoid air cell volume in 94 (188 ears) patients aged 5 to 12 months without a history of middle ear disease. MAIN OUTCOME MEASURES: Volume reconstruction was based on high-resolution computed tomography images using a three-dimensional reconstruction that is considered normal by radiologists. One-way analysis of variance and linear regression were used to determine the relationship between the volume and age in male and female subjects. RESULTS: Forty-eight scans were from male and 46 from female patients. In the age group from 5 to 12 months, the mastoid pneumatization was independent of age ( p > 0.05). There were no significant volume differences found between the age groups. Neither male/female nor right/left significant differences were observed in relation to the algebraic data of the mastoid air cells volume ( p > 0.05). CONCLUSIONS: Based on this analytic study, we are the first to use three-dimensional volume quantification based on high-resolution computed tomography in such large samples of early infancy. Because of its potential role as a susceptibility factor for otitis media and other otologic problems, it is important to describe the growth and development of mastoid pneumatization. More extensive clinical studies are needed to give a comprehensive insight into the air cell volume across age groups in different populations.

Fecal and serum metabolomic signatures and gut microbiota characteristics of allergic rhinitis mice model.

Background: The etiology of allergic rhinitis (AR) is complicated. Traditional therapy of AR still has challenges, such as low long-term treatment compliance, unsatisfactory therapeutic outcomes, and a high financial burden. It is urgent to investigate the pathophysiology of allergic rhinitis from different perspectives and explore brand-new possible preventative or treatment initiatives. Objective: The aim is to apply a multi-group technique and correlation analysis to explore more about the pathogenesis of AR from the perspectives of gut microbiota, fecal metabolites, and serum metabolism. Methods: Thirty BALB/c mice were randomly divided into the AR and Con(control) groups. A standardized Ovalbumin (OVA)-induced AR mouse model was established by intraperitoneal OVA injection followed by nasal excitation. We detected the serum IL-4, IL-5, and IgE by enzyme-linked immunosorbent assay (ELISA), evaluated the histological characteristics of the nasal tissues by the hematoxylin and eosin (H&E) staining, and observed the nasal symptoms (rubs and sneezes) to evaluate the reliability of the AR mouse model. The colonic NF-κB protein was detected by Western Blot, and the colonic histological characteristics were observed by the H&E staining to evaluate inflammation of colon tissue. We analyzed the V3 and V4 regions of the 16S ribosomal DNA (rDNA) gene from the feces (colon contents) through 16S rDNA sequencing technology. Untargeted metabolomics was used to examine fecal and serum samples to find differential metabolites. Finally, through comparison and correlation analysis of differential gut microbiota, fecal metabolites, and serum metabolites, we further explore the overall impact of AR on gut microbiota, fecal metabolites, and host serum metabolism and its correlation. Results: In the AR group, the IL-4, IL-5, IgE, eosinophil infiltration, and the times of rubs and sneezes were significantly higher than those in the Con group, indicating the successful establishment of the AR model. No differences in diversity were detected between the AR and Con groups. However, there were modifications in the microbiota's structure. At the phylum level, the proportion of Firmicutes and Proteobacteria in the AR group increased significantly, while the proportion of Bacteroides decreased significantly, and the ratio of Firmicutes/Bacteroides was higher. The key differential genera, such as Ruminococcus, were increased significantly in the AR group, while the other key differential genera, such as Lactobacillus, Bacteroides, and Prevotella, were significantly decreased in the Con group. Untargeted metabolomics analysis identified 28 upregulated and 4 downregulated differential metabolites in feces and 11 upregulated and 16 downregulated differential metabolites in serum under AR conditions. Interestingly, one of the significant difference metabolites, α-Linoleic acid (ALA), decreased consistently in feces and serum of AR. KEGG functional enrichment analysis and correlation analysis showed a close relationship between differential serum metabolites and fecal metabolites, and changes in fecal and serum metabolic patterns are associated with altered gut microbiota in AR. The NF-κB protein and inflammatory infiltration of the colon increased considerably in the AR group. Conclusion: Our study reveals that AR alters fecal and serum metabolomic signatures and gut microbiota characteristics, and there is a striking correlation between the three. The correlation analysis of the microbiome and metabolome provides a deeper understanding of AR's pathogenesis, which may provide a theoretical basis for AR's potential prevention and treatment strategies.

Inflammatory markers in children with obstructive sleep apnea syndrome.

Objective: To evaluate serum inflammatory markers of YKL-40, Interleukin-6 (IL-6), Interleukin-8(IL-8), Interleukin-10(IL-10), TNF-α(tumor necrosis factor-α), and CRP (C-reactive protein) in children with and without OSAS. Methods: The ELISA technique has been used to identify the concentration of inflammatory markers such as YKL-40, IL-6, IL-8, IL-10, TNF-α, and CRP in the serum of 83 children with OSAS and 83 children without OSAS. Results: Serum levels of YKL-40, IL-6, IL-8, and IL-10 were found to be increased in children with OSAS. YKL-40 was found to be positively correlated with IL-6 and IL-8, and negatively correlated with IL-10. At the same time,YKL-40 was also found to be positively correlated with OAHI and LoSpO2% in OSAS group. IL-8 was positively correlated with OAHI whereas IL-10 was positively correlated with LoSpO2. Conclusion: Children with OSAS are in a systemic inflammatory state. YKL-40 together with IL-8 may act as serum inflammatory markers and provide an indication for the diagnosis of children with OSAS.

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.

Heterogeneity and subtypes of CD4+ regulatory T cells: implications for tumor therapy.

In the conventional view, CD4+ regulatory T cell (Treg) represents a subset of lymphocytes that involve the perception and negative regulation of the immune response. CD4+Treg plays an important role in the maintenance of immune homeostasis and immune tolerance. However, recent studies have revealed that CD4+Treg do not suppress the immune response in some diseases, but promote inflammatory injury or inhibit tissue remodeling, suggesting the functional heterogeneity of CD4+Treg. Their involvement in tumor pathogenesis is more complex than previously understood. This article reviews the relevant research on the heterogeneity of CD4+Treg, subtype classification, and their relationship with tumor therapy.

Vancomycin-induced gut microbiota dysbiosis aggravates allergic rhinitis in mice by altered short-chain fatty acids.

Objective: This study aims to explore how gut microbiota dysbiosis affects allergic rhinitis (AR) and whether short-chain fatty acids (SCFAs) play a role in this process. Methods: A mouse gut microbiota dysbiosis model was established by adding vancomycin to drinking water for 2 weeks before ovalbumin (OVA) sensitization. Then an OVA-alum AR mouse model was established by intraperitoneal OVA injection followed by nasal excitation. Hematoxylin and eosin (H&E) staining was performed to observe pathological changes in nasal and colon tissues of AR mice. Serum levels of total-IgE, OVA-sIgE, IL-4, IL-5, IL-10, and TGF-ß1 were measured. The composition and diversity of the mouse gut microbiota were observed by 16S rDNA sequencing. Levels of SCFAs in feces were determined using SCFA-targeted metabolomics. Sodium butyrate (NaB) was added daily to mice on a low-fiber basal diet 2 weeks before the first sensitization, until the end of the study. Results: After gut microbiota dysbiosis, serum levels of the total IgE, OVA-sIgE, IL-4, and IL-5 in AR mice were significantly increased, compared with the control group. The composition and diversity of gut microbiota were significantly altered after gut microbiota dysbiosis, with the fecal SCFAs significantly reduced as well. The reduced bacterial genera after gut microbiota dysbiosis, such as Ruminococcus and Lactobacillus, were significantly and positively correlated with SCFAs. In contrast, the increased genera in the Van group, such as Escherichia-Shigella and Klebsiella, were significantly negatively correlated with SCFAs in feces. NaB treatment significantly reduced total-IgE, OVA-sIgE, IL-4, and IL-5 levels in serum, and inflammatory infiltration of the nasal and colon mucosa. In addition, serum levels of IL-10 and TGF-ß1 increased significantly after NaB treatment. Foxp3 protein in the colon was upregulated considerably after NaB intervention. Conclusion: Vancomycin-induced gut microbiota dysbiosis increased susceptibility and severity of AR, which is significantly related to reduced SCFA-producing bacteria, fecal SCFAs, and specific bacterial taxa. In addition, it was found that NaB alleviated low dietary fiber base-fed symptoms and immune status in AR mice.

3-Amino-1,2,4-triazole-derived graphitic carbon nitride for photodynamic therapy.

Graphitic carbon nitride (g-C3N4) has been shown as a promising visible-light photosensitizer for photodynamic therapy (PDT) application. Nevertheless, its therapeutic efficiency is limited by the low efficiency of visible-light utilization. To overcome this issue, 3-amino-1,2,4-triazole-derived graphitic carbon nitride nanosheets (g-C3N5 NSs) are prepared for PDT application. The addition of nitrogen-rich triazole group into the g-C3N4 motif significantly makes the light absorption of g-C3N5 NSs red-shift with the band gap down to 1.95 eV, corresponding to a absorption edge at a wavelength of 636 nm. g-C3N5 NSs generate superoxide anion radicals (O2•-) and singlet oxygen (1O2) under the irradiation of a low-intensity white light emitting diode. Owing to the high efficiency of visible-light utilization, g-C3N5 NSs show about 9.5 fold photocatalytic activity of g-C3N4 NSs. In vitro anticancer studies based on the results of CCK-8 assay, Calcein-AM/PI cell-survival assay and photo-induced intracellular ROS level analysis in living HeLa cells demonstrate the potential of g-C3N5 NSs as a low-toxic and biocompatible high-efficient photosensitizer for PDT.

Long-term survival trend after primary total laryngectomy for patients with locally advanced laryngeal carcinoma.

Purpose: To evaluate long-term survival trends after primary total laryngectomy (TL) for locally advanced laryngeal carcinoma (LC). Methods: A total of 2094 patients diagnosed with locally advanced LC and underwent primary TL (1992-2011, at least 5-year follow-up) in the Surveillance, Epidemiology, and End Results (SEER) database were included in this study. Besides the traditional overall survival (OS) and cancer-specific survival (CSS) by using Kaplan-Meier curves, the 3-year conditional survival analysis was also performed to describe the long-term trends in these patients. Time-dependent multivariate competing-risk models were constructed to assess the persistent sub-distribution hazard of prognostic factors. Finally, a nomogram was developed to predict conditional cancer-specific survival. Results: The curves of overall hazard and cancer-specific hazard both quickly reached the apex within the first year since TL, then decreased thereafter. In general, the CS3 steadily increased from within 5 years after TL. In the stratified CS3 analysis, the increments in patients with adverse characteristics were more pronounced. 4 years after TL, the probability of surviving the next year exceeded 90%. The time-dependent multivariate competing-risk models indicated that age and lymph node ratio (LNR) persistently contributed to the cancer-specific outcome. The nomogram based on the competing-risk model was constructed to estimate CSS probability conditional upon 3 years for advanced LC patients having survived 1, 2, and 3 years. Conclusion: Most patients achieved a substantially improved survival rate after surviving a long period after primary TL. Patients diagnosed at older age and with higher LNR should receive more effective follow-up. The predictive nomogram can provide significant evidence for clinical research and practice.

Study on the correlation between OSAS and thoracic deformity in children: A retrospective single-center study in China.

OBJECTIVE: To evaluate the correlation between obstructive sleep apnea syndrome (OSAS) and the development of thoracic deformity in Children. METHODS: A retrospective analysis was performed with the medical records of 39 pediatric OSAS patients with thoracic deformity and matching 39 without thoracic deformity as control group between January 2015 and June 2019. The contrast was performed with age, gender, height, weight, body mass index (BMI), apnea/hypopnea index (AHI), the lowest oxyhemoglobin saturation (loSpO2)at night, tonsil and adenoid size, Alkaline phosphatase (ALP)and trace elements and metals between two groups. RESULTS: BMI, AHI, the lowest SpO2, Phosphorus and Zinc were the risk factors of thoracic deformity. Age, gender, disease history, the size of tonsil and adenoid, ALP and other trace elements were no significant difference occurred between two groups. CONCLUSION: OSAS characterized by apnea and hypoxia which are caused by narrow upper airway may be one cause of thoracic deformity in children. Pediatricians, thoracic and otolaryngologic surgeons should be alert to OSAS when thoracic deformities are diagnosed in children.

Phenyl doped graphitic carbon nitride nanosheets for sensing of copper ions in living cells.

Copper (Cu) is a vital metal element for humans and animals. Monitoring and evaluating the concentration level of Cu2+ in a biological body is an effective way to prevent a variety of diseases. In this work, phenyl doped graphitic carbon nitride (PDCN) nanosheets with strong green fluorescence exhibited a sensitive and selective detection for Cu2+ with a linear range from 0.1-2.0 µmol L-1. Furthermore, fluorescent imaging was applied to semiquantitatively detect Cu2+ in HeLa cells using PDCN nanosheets as the probe, which can avoid the interference of background autofluorescence. This work provided a low-cost and biologically friendly fluorescent probe to monitor the concentration level of Cu2+ in living cells.

The primary tumor resection in patients with distant metastatic laryngeal carcinoma.

BACKGROUND: The role of primary tumor resection in patients with distant metastatic laryngeal carcinoma (DMLC) has not been clarified completely. Thus, we used propensity score matching (PSM) and survival analysis to address this issue. METHODS: The PSM was utilized to avoid selection bias and disproportionate distributions of the confounding factors. Kaplan-Meier estimates and Cox proportional hazard analysis were utilized to evaluate overall survival (OS) and cancer-specific survival (CSS). RESULTS: From the Surveillance, Epidemiology, and End Results Program database, a cohort of 480 patients with DMLC were included. After PSM, the OS and CSS for patients who underwent resection were significantly longer than those without resection (median OS: 19 months vs. 8 months, P < 0.001; median CSS: 19 months vs. 9 months, P = 0.002). Tumor resection significantly prolonged survival of DMLC patients with appropriate demographic and clinical characteristics. In the multivariate analysis, age at diagnosis, race, pathologic subtype, and marital status were found significantly affecting both OS and CSS of patients who underwent surgical resection. Predictive nomograms were developed to help distinguish patients with early mortality potential after surgical resection. CONCLUSIONS: This study is the first one using PSM to assess the role played by surgical resection in DMLC and evaluate the prognostic factor of resected patients. Premised on well controlled postoperative complications, resection could significantly prolong OS and CSS of certain patients.

Fluorescence imaging of Cys in keratinocytes upon UVB exposure using phenyl doped graphitic carbon nitride Nanosheets-Au nanoparticles nanocomposite.

Ultraviolet B (UVB) irradiation induces the generation of reactive oxygen species (ROS) and causes damages to human skin. The depletion of glutathione (GSH) to scavenge ROS can protect skin cells from oxidative damage. However, little is known about the concentration level changes of cysteine (Cys), a precursor of GSH in skin cells after exposure to UVB irradiation. Herein, phenyl doped graphitic carbon nitride nanosheets-Au nanoparticles nanocomposite was prepared by in situ deposition of Au nanoparticles on the surface of phenyl doped graphitic carbon nitride nanosheets and showed a turn-on fluorescence response toward Cys over homocysteine, glutathione under physiological conditions. In the presence of Cys, remarkable enhancement of green fluorescence was observed. This nanocomposite was successfully applied for fluorescence imaging of Cys in human skin epidermal cells and monitoring the changes of Cys concentration level under the oxidative stress upon exposure to UVB irradiation in keratinocytes. It was found that the concentration of Cys was increased in the initial period after exposure to UVB irradiation and then gradually decreased to the normal level for the synthesis of GSH to defense the oxidative stress. Our result helps to understand the physiological function of Cys in human skin cells under UVB exposure.

Influence of POLG on Radiosensitivity of Nasopharyngeal Carcinoma Cells.

BACKGROUND AND OBJECTIVE: There is a high incidence of nasopharyngeal carcinoma (NPC), malignant head and neck tumors, in southern China. Radioresistance is the main cause affecting the efficacy of NPC treatments. The POLG gene particularly plays an important role in radiation-induced damage repair. In this study, the authors established RNAi CNE-1 and CNE-2 knockdown in two NPC cell lines to observe whether this gene affects the radiosensitivity of NPC cells. MATERIALS AND METHODS: Four short hairpin RNA (shRNA) expression plasmids targeting POLG gene were constructed and transfected into the NPC cell lines CNE-1 and CNE-2. Screening was performed to evaluate the stable expression of cloned cells, which were named CNE-1/POLG-shRNA1, CNE-1/POLG-shRNA2, CNE-2/POLG-shRNA1, and CNE-2/POLG-shRNA2. The negative controls CNE-1/Neg-shRNA and CNE-2/Neg-shRNA were additionally used. The MTT method, flow cytometry, clone formation analysis, cell migration, and other experimental methods were employed to verify changes in the radiosensitivity of the NPC cells. RESULTS: Fluorescent quantitative PCR and Western blot confirmed the downregulation of the PLOG gene through diminished PLOG messenger RNA and protein levels. Consequently, the authors report the stable knockdown of the POLG gene in an NPC model. Dose-dependent radiation exposure of POLG inhibited NPC cell growth and increased apoptosis compared with control cells (p < 0.01), as demonstrated through colony formation assay and flow cytometry. Functional assays indicated that knockdown of the POLG in CNE-1 and CNE-2 cells remarkably reduced cell viability and proliferation. Specifically, POLG knockdown led to G1 phase arrest and apoptosis. CONCLUSIONS: Overall, the authors conclude that POLG downregulation alters the radiosensitivity of NPC cells, indicating that the gene is likely involved in conferring the radiation response of the cells. In addition, findings in this study suggest a novel role for POLG as a potential predictive marker for NPC radiotherapy efficiency. POLG gene can be used as a potential clinical target to effectively improve the radiosensitivity of NPC.

Defining the regulatory role of programmed cell death 4 in laryngeal squamous cell carcinoma.

Programmed cell death 4 (PDCD4) is decreased in many different kinds of malignant tumors. EMT endows tumor cells invasive and metastatic properties. However, few studies have determined the role of PDCD4 in the regulation of EMT in the context of laryngeal carcinoma. We examined the relationship between PDCD4 and EMT-associated proteins E-cadherin and N-cadherin using laryngeal carcinoma tissues. Gene manipulation was used to define the regulatory capacity of PDCD4. We report that PDCD4 and E-cadherin/N-cadherin expression were significantly changed in the carcinoma tissues, and their expression was associated with pathological grade, metastatic state, and clinical stage. The suppression of PDCD4 (and consequently, E-cadherin) was concomitant with increased proliferation and G2-phase arrest, decreased apoptosis, and increased cell invasion. PDCD4 upregulation reversed the above-mentioned results. In nude mice, PDCD4 knockdown increased tumor growth and pathological features, confirming the tumorigenic role of PDCD4. Finally, PDCD4 silencing was associated with dysregulation of the carcinogenic Wnt-ß-catenin and the STAT3-miR-21 signaling pathways. This study revealed a dynamic regulatory relationship between PDCD4 and critical factors for EMT, establishing a broad, functional role for PDCD4 in laryngeal carcinoma, which may be propagated by the STAT3-miR-21 pathway. These findings provide new information on an EMT-associated target that may lead to a novel therapy.