[A case report of nasopharyngeal inflammatory myofibroblastoma in infant].

Inflammatory myofibroblastic tumor （IMT） is a rare mesenchymal soft tissue tumor characterized by borderline or low-grade malignancy. It is rare childhood tumor with an average age of onset of 10 years old. It is even rarer in infants and toddlers, and the etiology and pathogenesis of this tumor are still unclear. The clinical presentation of IMT is non-specific and are related to the location of the tumor. When the tumor compresses adjacent organs, it can cause pain and functional impairment. According to the current literature, IMT is most commonly found in the digestive and respiratory systems, but also occasionally occur in the genitourinary system, head and neck, and limbs. At present, there have been no reports of nasopharyngeal IMT involving nasal cavity of infants and toddlers at home and abroad.This article reports a case of a massive inflammatory myofibroblastic tumor involving the nasal cavity and nasopharynx in an infant. Plasma-assisted minimally invasive surgery was performed through multiple surgical approaches and achieved satisfactory therapeutic results. This case report may provide valuable reference for the treatment of similar diseases.

[Two children with late-onset congenital central hypoventilation syndrome].

Two children with late-onset congenital central hypoventilation syndrome were reported, one of whom was male and had no abnormal manifestations after birth, respiratory failure occurs at the age of 1 year and 6 months. After being hospitalized, he was treated with oxygen inhalation and non-invasive ventilation, but carbon dioxide retention could not be corrected. After one month of tracheal intubation, he was failure to wean from ventilator, so tracheostomy was performed. He needs a ventilator to help breath while sleeping, and can breath autonomously during the day without ventilator. The other case was a female, with no abnormalities after birth. At the age of 11 months, she developed respiratory failure. During sleep, the child needs non-invasive assisted ventilation through a nasal mask, and during the day, she breathed autonomously.Two patients were followed up forever 2 years and their growth and development were normal.

The transcription factor XBP1 in dendritic cells promotes the TH2 cell response in airway allergy.

Dendritic cells (DCs) that express T cell immunoglobulin domain molecule-4 (TIM4), a cell surface receptor for phosphatidylserine, induce T helper 2 (TH2) cell responses and allergic reactions. We elucidated the role of the transcription factor X-box-binding protein-1 (XBP1) in the induction of the TH2 cell response through its role in generating TIM4+ DCs. We found that XBP1 was required for TIM4 mRNA and protein expression in airway DCs in response to the cytokine interleukin-2 (IL-2) and that this pathway was required for TIM4 expression on DCs in response to the allergens PM2.5 and Derf1. The IL-2-XBP1-TIM4 axis in DCs contributed to Derf1/PM2.5-induced, aberrant TH2 cell responses in vivo. An interaction between the guanine nucleotide exchange factor Son of sevenless-1 (SOS1) and the GTPase RAS promoted XBP1 and TIM4 production in DCs. Targeting the XBP1-TIM4 pathway in DCs prevented or alleviated experimental airway allergy. Together, these data suggest that XBP1 is required for TH2 cell responses by inducing the development of TIM4+ DCs, which depends on the IL-2-XBP1-SOS1 axis. This signaling pathway provides potential therapeutic targets for the treatment of TH2 cell-dependent inflammation or allergic diseases.

[Preliminary analysis of the effect of individualized voice therapy on pediatric voice disorders].

Objective:To determine the effectiveness of individualized voice therapy in persistent pediatric voice disorders. Methods:Thirty-eight children who were admitted to the Department of Pediatric Otolaryngology Shenzhen Hospital, Southern Medical University due to persistent voice disorder from November 2021 to October 2022 were included. All children were evaluated by dynamic laryngoscopy before voice therapy. Two voice doctors performed GRBAS score and acoustic analysis on the children's voice samples to obtain the relevant parameters including F0, Jitter, Shimmer, and MPT; All children were given personalized voice therapy for 8 weeks. Results:Among 38 children with voice disorders, 75.8%（29 cases） were diagnosed with vocal nodules, 20.6%（8 cases） were vocal polyps, and 3.4%（1 case） were vocal cysts. And in all children. And 51.7%（20 cases） had the sign of supraglottic extrusion under dynamic laryngoscopy. GRBAS scores decreased from 1.93 ± 0.62, 1.82 ± 0.55, 0.98 ± 0.54, 0.65 ± 0.48, 1.05 ± 0.52 to 0.62 ± 0.60, 0.58 ± 0.53, 0.32 ± 0.40, 0.22 ± 0.36, 0.37 ± 0.36. F0, Jitter, Shimmer decreased from（243.11±39.73） Hz, （0.85±0.99）%, （9.96±3.78）% to（225.43±43.20） Hz, （0.33±0.57）%, （7.72±4.32）%, respectively MPT was prolonged from（5.82±2.30） s to（7.87±3.21） s after treatment. All parameters changes had statistical significance. Conclusion:Voice therapy can solve children's voice problems, improve their voice quality and effectively treat children's voice disorders.

[Mechanism of Der f 1/IGF-1 nanoparticle promoting the production of regulatory T cell].

Objective:To prepare PLGA nanoparticles loaded with Der f 1/IGF-1（Der f 1/IGF-1 NPs） and investigate their role in promoting the formation of Treg cells. Methods:NPs coated with Der f 1/IGF-1 were prepared by double emulsion method and their physicochemical properties and cumulative release rate in vitro were analyzed. After pretreatment, BMDC was divided into Saline group, Blank NPs group, Der f 1/IGF-1 group and Der f 1/IGF-1 NPs group. Determination of the expression of IL-10 and TGF-ß in BMDC by ELISA. The number of Treg cells was detected by flow cytometry. Results:The results showed that Der f 1/IGF-1 NPs were spherical structures, with good dispersion, particle size less than 200 nm, negative charge and stable slow-release effect of Zeta potential. After BMDC pretreatment, the expression levels of TGF-ß and IL-10 in BMDC cells in the Der f 1/IGF-1 NPs group were significantly increased compared with the Blank NPs group, and the difference was statistically significant（P<0.001）. After co-culture with CD4+ T cells, the proportion of Treg cells produced in the Der f 1/IGF-1 NPs group was significantly increased, and the difference was statistically significant（P<0.001）. Conclusion:Der f 1/IGF-1 NPs can induce Treg cell generation in vitro. This study provides a new and more effective method for the reconstruction of immune tolerance dysfunction.

Multicentre clinical study of haemorrhage after coblation tonsillectomy in children: a prospective study protocol.

INTRODUCTION: Post-tonsillectomy haemorrhage (PTH) is the most common and significant life-threatening complication following tonsillectomy, especially in children. Coblation tonsillectomy (CTE) at low temperature is extensively used in China and has gradually replaced conventional tonsil dissection. However, risk of late PTH has been shown to increase with the use of hot instruments. The aim of this study is to detect post-CTE haemorrhage (PCTH) rates and analyse risk factors of PCTH in China, through a nationwide multicentre prospective study. METHODS AND ANALYSIS: This investigator-initiated, prospective, multicentre clinical trial will involve children with tonsil disease who will undergo CTE from 22 research centres in different cities in China. All operations will be performed using the same technique of extracapsular tonsillectomy. Data will be collected for all patients enrolled in this study through a preoperative visit, intraoperative data and a postoperative visit. The measurement data conforming to a normal distribution will be expressed by means±SDs, and a Student's t-test will be used for comparison. The comparison among groups of counting data will be expressed by percentage or rate, and a χ2 test will be used for comparison. Non-conditional logistic regression analysis will be used to analyse the preoperative, intraoperative and postoperative risk factors for haemorrhage rate after CTE. P<0.05 will be considered statistically significant. ETHICS AND DISSEMINATION: This study protocol was approved by the Ethics Committee of Shanghai Children's Hospital/Shanghai Jiao Tong University (reference number 2021R096-E01). All patients will provide written informed consent. Results of this study are to be published in respected, peer-reviewed journals and findings presented at scientific conferences in the field of paediatric otorhinolaryngology. TRIAL REGISTRATION NUMBER: NCT05206799.

TAFA4-IL-10 axis potentiate immunotherapy for airway allergy by induction of specific regulatory T cells.

Allergen-specific immunotherapy (AIT) is the main treatment for allergic diseases. The therapeutic efficacy of AIT has to be improved. Neuropeptides, such as TAFA4, have immune-regulating features. The objective of this study is to promote the efficacy of AIT in experimental allergic rhinitis (AR) by the concurrent use of TAFA chemokine as a family member 4 (TAFA4). In this study, an AR mouse model was developed using ovalbumin (OVA) as the specific antigen. The AR response was assessed in mice after treatment with AIT or/and TAFA4. We found that exposure to TAFA4 activated dendritic cells (DCs) in the airway tissues. Activation of DC by TAFA4 resulted in the expression of IL-10. TAFA4 also promoted the activities of c-Maf inducing protein. The FPR1-MyD88-AKT signal pathway was associated with the TAFA4-induced Il10 expression in the DCs. Co-administration of AIT/TAFA4 attenuated the AR response in mice by inducing antigen-specific Tr1 cells. In conclusion, TAFA4 induces the expression of IL-10 in DCs. Acting as an adjuvant, TAFA4 significantly improves AIT's therapeutic efficacy against AR by inducing antigen-specific Tr1 cells.

Rnf20 inhibition enhances immunotherapy by improving regulatory T cell generation.

BACKGROUND: Allergic disorders are common all over the world. The pathogenesis of allergy is unclear. Therapies for allergic disorders require improvement. Endoplasmic reticulum (ER) stress is one of the factors influencing immune response. The purpose of this study is to improve the effectiveness of immunotherapy for experimental respiratory allergy by targeting the ER stress signal pathway. METHODS: Committed CD4+ T cells were isolated from blood samples collected from patients with allergic rhinitis (AR) and TCR ovalbumin transgenic mice. The effects of TCR engagement and 3-methyl-4-nitrophenol (MNP) on inducing ER stress in committed CD4+ T cells were evaluated. RESULTS: ER stress was detected in antigen-specific CD4+ T cells (sCD4+ T cells) of AR patients. The environmental pollutant MNP increased the expression of the X-binding protein-1 (XBP1) in the committed CD4+ T cells during the TCR engagement. XBP1 mediated the effects of MNP on inhibiting regulatory T cell (Treg) generation. The effects of MNP on induction of protein 20 (Rnf20) in CD4+ T cells were mediated by XBP1. Inhibition of Rnf20 rescued the Treg development from MNP-primed sCD4+ T cells. The ablation of Rnf20 improved the immunotherapy of AR through the restoration of the Treg generation. CONCLUSIONS: ER stress can be detected in CD4+ T cells in TCR engagement. Exposure to MNP exacerbates ER stress in committed CD4+ T cells. Regulation of the ER stress-related Rnf20 expression can restore the generation of Treg from CD4+ T cells of subjects with allergic diseases.

[Preliminary study on efficacy and safety of submucosal plasma ablation of inferior turbinate in children with allergic rhinitis complicated with obstructive sleep apnea syndrome].

Objective:This study aimed to investigate the long-term clinical efficacy and safety of inferior turbinate submucosal plasma ablation combined with or without tonsillar and adenoid surgery in children with allergic rhinitis（AR） combined with obstructive sleep apnea syndrome（OSAS） who were ineffective after conservative systemic treatment. Methods:A total of 43 children with AR complicated with OSAS who met the inclusion criteria among 68 children hospitalized from January 2019 to February 2022 were retrospectively analyzed. The data were collected, including the clinical characteristics, surgical methods perioperative management and prevention and treatment of complications. Moreover, one year follow-up was performed to compare the VAS scores of children before and after surgery, and to evaluate their mid-term and long-term outcomes. Results:The average operation time was 36 minutes, meanwhile, the intraoperative blood was limited. The symptoms of nasal congestion, runny nose, sleep snoring, and mouth breathing were significantly improved after operation, and the results were satisfactory after one-year follow-up without complications such as bleeding, hematoma, intraoperative adhesion, and nasal dryness. Conclusion:Submucosal plasma ablation of inferior turbinate with or without tonsillectomy adenoidectomy in children with AR can effectively improve the clinical symptoms of AR combined with OSAS children who are ineffective after conservative treatment. It can improve the symptoms of sleep-disordered breathing such as sleep snoring and mouth breathing, with good mid-and long-term curative effects and fewer complications, which is an effective and safe treatment for children with AR combined with OSAS.

Noninvasive ventilation via bilevel positive airway pressure improved sleep in a child with congenital central hypoventilation syndrome: A case report.

We report the polysomnography findings of a 2-year-old girl who was previously diagnosed with CCHS and treated with bilevel positive airway pressure (BiPAP) and O2 supplementation for a year. The girl had convulsions 2 times in the last 10 days. After we replaced her nasal cannula with a nasal mask and adjusted the parameters of the BiPAP, her sleep and ventilation were improved. The polysomnographies measured under spontaneous breathing without oxygen supplementation showed that her sleep structure, heart rate, and oxygen saturation during sleep were improved 1 month and 1 year after effective BiPAP treatment.

[Application of multimodal combined surgical strategy in children with intractable laryngeal airway obstruction].

Objective:To explore the selection of surgical methods and intraoperative strategies for the treatment of children with intractable laryngeal airway obstruction, and to provide new options for the diagnosis and treatment of children with intractable laryngeal airway obstruction. Methods:The clinical data of 12 children with intractable laryngeal airway obstruction treated by our team from January 2005 to December 2021 were retrospective analyzed. All the children were treated with minimally invasive surgery under rigid bronchoscope or suspension laryngoscope combined with electronic endoscope. The surgical methods included laryngeal microsurgery, plasma ablation, balloon dilatation, drug-eluting stents, laser ablation, endoscopic snare, etc. The patients were followed up after operation. Results:All patients completed the operation under general anesthesia, and there were no intraoperative or postoperative complications. Except for one patient with bilateral vocal cord paralysis who failed to extubation due to restenosis, the others were successfully extubated after operation. Among them, 9 cases of benign space-occupying obstruction were followed up for 5-60 months without recurrence, and 2 cases of malignant tumor-induced obstruction were followed up for 24 months（acinar cell carcinoma） and 36 months（mucoepidermoid carcinoma） without recurrence. Conclusion:Endoscopic multi-operation is effective for children with intractable obstruction. Compared with traditional thoracotomy, endoscopic multi-operation strategies has the advantages of less trauma, faster and safer. For different sizes, locations and pathological types of obstruction, different surgical equipment and methods should be combined.

Superior Thermoelectric Performance of Robust Column-Layer ITO Thin Films Tuning by Profuse Interfaces.

Indium tin oxide (ITO) thin films suffer from poor chemical stability at high temperatures because of the instability of point defects and structural variations. An interface design strategy was proposed herein to improve this situation, where a robust ITO-based thin film with a column-layer structure was fabricated. Three types of column-layer ITO thin films were fabricated via magnetron sputtering. By tuning the interfaces, we controlled the effective mass and weighted mobility, enhancing the electrical conductivity (2.17 × 106 S m-1) and power factor (1138 µW m-1 K-2). The crack propagation path was prolonged because of the profuse interfaces between the columns and layers in the alternate thin films. Thus, enhanced nanohardness (16.5 GPa) was obtained. The structural evolution and performance of the column-layer ITO thin films annealed under different conditions were investigated. The atoms were restricted by the profuse interfaces, resulting in high-temperature stability. The results demonstrate that the interface design of ITO thin films can efficiently modify the stability of conductive ceramics over a wide temperature range, which has significant potential for applications in microdevices and aero engines.

[Low temperature plasma ablation and drug stent implantation for laryngotracheal atresia: a case report].

This paper reports a case of acquired laryngosis stenosis treated by arc plasma ablation, drug stent implantation and balloon dilatation. The patient with difficulty in pulling out the tube after intubation 3 years ago was diagnosed with laryngotracheal stenosis and treated with tracheotomy, in order to extubation. Physical examination showed that the metal trachea cannula in front of the neck was in position, unobstructed, and can be seen slightly inspiratory three concave sign when moving. CT and laryngoscope showed subglottic stenosis or atresia. After the operation, the children successfully removed the tracheal tube, after half a year, the laryngotracheal was unobstructed, the children had smooth breathing, no shortness of breath, and normal activities and diet.

Highly oriented platinum/iridium thin films for high-temperature thermocouples with superior precision.

The long-term precise high-temperature measurement of thin-film thermocouples (TFTCs) has attracted attention due to the capability of instantaneous temperature detection. However, related technologies have seen slow development, and there is no one standard TFTC yet. Here, we focus on a new strategy of reducing alloys for the easy preparation and performance enhancement of TFTCs via nanostructure and interface design. To this end, we fabricated a platinum/iridium (Pt/Ir) pure-element TFTC with a well matched interface and few defects, which demonstrated excellent long-term service stability over a high-temperature range. The corresponding polynomial fitting coefficients were ≥0.99999, indicating the accurate acquisition of temperature data. A reduced deviation (<0.21%) between three calibration cycles was obtained over a wide temperature range of 300 °C to 1000 °C, which is better than the maximum precision of a standard wire thermocouple. Superior properties are achieved because of the resulting fewer defects in the Pt and Ir thin films with highly preferential orientation along the (111) plane. The results indicate that our Pt/Ir TFTCs have significant potential for application in many domains such as thermal detection, microelectronics and aero-engines.

Superoxide Dismutase Prevents SARS-CoV-2-Induced Plasma Cell Apoptosis and Stabilizes Specific Antibody Induction.

The infection of coronavirus disease (COVID-19) seriously threatens human life. It is urgent to generate effective and safe specific antibodies (Abs) against the pathogenic elements of COVID-19. Mice were immunized with SARS-CoV-2 spike protein antigens: S ectodomain-1 (CoV, in short) mixed in Alum adjuvant for 2 times and boosted with CoV weekly for 6 times. A portion of mice were treated with Maotai liquor (MTL, in short) or/and heat stress (HS) together with CoV boosting. We observed that the anti-CoV Ab was successfully induced in mice that received the CoV/Alum immunization for 2 times. However, upon boosting with CoV, the CoV Ab production diminished progressively; spleen CoV Ab-producing plasma cell counts reduced, in which substantial CoV-specific Ab-producing plasma cells (sPC) were apoptotic. Apparent oxidative stress signs were observed in sPCs; the results were reproduced by exposing sPCs to CoV in the culture. The presence of MTL or/and HS prevented the CoV-induced oxidative stress in sPCs and promoted and stabilized the CoV Ab production in mice in re-exposure to CoV. In summary, CoV/Alum immunization can successfully induce CoV Ab production in mice that declines upon reexposure to CoV. Concurrent administration of MTL/HS stabilizes and promotes the CoV Ab production in mice.

Glutaminolysis is required in maintaining immune regulatory functions in B cells.

IL-10-expressing regulatory B cells (B10 cells) are dysfunctional in patients with many immune disorders. The underlying mechanism remains to be further elucidated. Glutamine is an essential nutrient for cell metabolism. This study aims to elucidate the role of glutaminolysis in maintaining the immune regulatory capacity in B10 cells. Peripheral blood samples were collected from 50 patients with allergic rhinitis and 50 healthy control subjects. B cells were isolated from blood samples by cell sorting with flow cytometry. The role of glutaminolysis in regulating B10 cell activities was assessed by immunological and biochemical approaches. The results showed that B cells from patients with allergic rhinitis expressed low levels of the transporter of glutamine and neutral amino acid. Glutaminolysis was required in the IL-10 expression in B cells. The glutamine catabolism was required in B10 cell generation. The mTOR activation mediated the glutaminolysis-associated B10 cell induction, and the suppression of the B cell glycogen synthase kinase-3 (GSK3) activation. GSK3 activation suppressed IL-10 expression in B cells. Inhibition of GSK3 enhanced IL-10 expression in B cells and alleviated experimental allergic rhinitis by generating immune competent type 1 regulatory T cells.

Flagellin Alleviates Airway Allergic Response by Stabilizing Eosinophils through Modulating Oxidative Stress.

Eosinophil (Eo) degranulation plays a central role in the initiations of allergic attacks. Flagellin (FGN), the major component of bacterial flagella, has immune regulatory functions. This study aims to investigate the role of FGN in alleviating the allergic reaction by stabilizing Eos. A toll-like receptor 5-knockout mouse strain was employed to test the role of FGN in stabilizing Eos. An airway allergy mouse model was developed to test the administration of FGN in alleviating the airway allergy by stabilizing Eos. The results showed that FGN was required in stabilizing Eos in the airway tissues. FGN prevented specific antigen-induced Eo activation. Oxidative stress was associated with the antigen-induced Eo activation that could be counteracted by the presence of FGN. The FGN levels were lower and chymase levels were higher in the airway tissues of mice with allergic inflammation. Negative correlation was detected between the data of FGN and chymase in the lung tissues. Chymase physically contacted FGN to speed up its degradation. The administration of FGN alleviated experimental allergic inflammation in the mouse airways by stabilized Eos in the lung tissues. In conclusion, FGN contributes to Eo stabilization. The administration of FGN alleviates the experimental airway allergy. The data suggest that FGN can be a candidate to be employed in the treatment of allergic disorders.

Livin in synergy with Ras induces and sustains corticosteroid resistance in the airway mucosa.

Rationale: Corticosteroid resistance (CR) seriously affects the therapeutic effects of steroids on many chronic inflammatory disorders, including airway allergy. The mechanism of CR development is unclear. Recent research indicates that livin, an apoptosis inhibitor, is associated with the regulation in cell activities. This study investigates the role of livin in the inducing and sustaining CR in the airway mucosa. Methods: Nasal epithelial cells (NECs) were isolated from surgically removed nasal mucosal tissues of patients with allergic rhinitis (AR) and nasal polyps with or without CR. Differentially expressed genes in NECs were analyzed by the RNA sequencing. A CR mouse model was developed to test the role of livin in CR development. Results: The results showed that NECs of AR patients with CR expressed high levels of livin, that was positively correlated with the thymic stromal lymphopoietin (TSLP) expression and the high Ras activation status in NECs. Livin and Ras activation mutually potentiating each other in the inducing and sustaining the TSLP expression in NECs. TSLP induced eosinophils and neutrophils to express glucocorticoid receptor-ß (GRß). Eosinophils and neutrophils with high CRß expression were resistant to corticosteroids. Depletion of livin or inhibition of TSLP markedly attenuated CR and airway allergy. Conclusions: Livin facilitates CR development in the airways by promoting TSLP expression in epithelial cells and the GRß expression in eosinophils and neutrophils. Depletion of livin or inhibiting TSLP attenuates CR development and inhibits airway allergy, this has the translational potential to be used in the treatment of airway allergy.