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.

Modulating oxidative stress counteracts specific antigen-induced regulatory T-cell apoptosis in mice.

Treg are known to have a central role in orchestrating immune responses, but less is known about the destiny of Treg after being activated by specific Ags. This study aimed to investigate the role of superoxide dismutase, an active molecule in the regulation of oxidative stress in the body, in the prevention of Treg apoptosis induced by specific Ags. Ag-specific Tregs were isolated from the DO11.10 mouse intestine. A food allergy mouse model was developed with ovalbumin as the specific Ag and here, we observed that exposure to specific Ag induced Treg apoptosis through converting the precursor of TGF-ß to its mature form inside the Tregs. Oxidative stress was induced in Tregs upon exposure to specific Ags, in which Smad3 bound the latency-associated peptide to induce its degradation, converting the TGF-ß precursor to its mature form, TGF-ß. Suppressing oxidative stress in Tregs alleviated the specific Ag-induced Treg apoptosis in in vitro experiments and suppressed experimental food allergy by preventing the specific Ag-induced Treg apoptosis in the intestine. In conclusion, exposure to specific Ags induces Treg apoptosis and it can be prevented by upregulating superoxide dismutase or suppressing reactive oxidative species in Tregs.

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.

Epithelial cell-derived CD83 restores immune tolerance in the airway mucosa by inducing regulatory T-cell differentiation.

The mechanism of generation of regulatory T cells (Treg) remains incompletely understood. Recent studies show that CD83 has immune regulatory functions. This study aims to investigate the role of epithelial cell-derived CD83 in the restoration of immune tolerance in the airway mucosa by inducing the Treg differentiation. In this study, CD83 and ovalbumin (OVA)-carrying exosomes were generated from airway epithelial cells. An airway allergy mouse model was developed to test the role of CD83/OVA-carrying exosomes in the suppression of airway allergy by inducing Treg generation. We observed that mouse airway epithelial cells expressed CD83 that could be up-regulated by CD40 ligand. The CD83 deficiency in epithelial cells retarded the Treg generation in the airway mucosa. CD83 up-regulated transforming growth factor-ß-inducible early gene 1 expression in CD4+ T cells to promote Foxp3 expression. Exposure of primed CD4+ T cells to CD83/OVA-carrying exosomes promoted antigen-specific Treg generation. Administration of CD83/OVA-carrying exosomes inhibited experimental airway allergic response. In summary, airway epithelial cells express CD83 that is required in the Treg differentiation in the airway mucosa. Administration of CD83/OVA-carrying exosomes can inhibit airway allergy that has the translation potential in the treatment of airway allergic disorders.

Interaction between Ras and Bcl2L12 in B cells suppresses IL-10 expression.

The pathogenesis of recurrent tonsillitis is to be further investigated. B cell-derived interleukin (IL)-10 plays a critical role in immune regulation. Ras activation plays an important role in cancer and many immune disorders. This study aims to investigate the role of Ras activation in down regulating IL-10 expression in tonsillar B cells. Surgically removed tonsil tissues were collected from patients with recurrent acute tonsillar inflammation; B cells were isolated from the tonsillar tissues by flow cytometry sorting to be analyzed by the Ras-specific enzyme-linked immunosorbent assay and pertinent immunological approaches. We found that, compared to peripheral B cells (pBC), B cells isolated from the tonsillar tissues with recurrent inflammation (tBC) showed higher Ras activation, lower IL-10 expression and higher Bcl2L12 expression. Bcl2L12 formed a complex with GAP (GTPase activating protein) to prevent Ras from deactivating. The Ras activation triggered the MAPK/Sp1 pathway to promote the Bcl2L12 expression in B cells. Bcl2L12 prevented the IL-10 expression in tBCs, that was counteracted by inhibition of Ras or the Ras signal transduction pathway. In conclusion, Bcl2L12 interacts with Ras activation to compromise immune tolerance in the tonsils by inhibiting the IL-10 expression in tBCs. Inhibition of Bcl2L12 can restore the IL-10 expression in tBCs.

Twist1 sustains the apoptosis resistance in eosinophils in nasal mucosa of allergic rhinitis.

Eosinophils (Eos) are the canonical effector cells in allergic rhinitis (AR) and many inflammatory diseases. The mechanism of eosinophilia occurring in the lesion sites is not fully understood yet. Twist1 protein (Twist, in short) is an apoptosis inhibitor that also has immune regulatory functions. This study aims to investigate the role of Twist in the pathogenesis of eosinophilia in AR. In this study, surgically removed human nasal mucosal samples were obtained from patients with chronic sinusitis and nasal polyps with AR (the AR group) or without AR (the nAR group). Eos were isolated from the samples by flow cytometry. We found that abundant Eos were obtained from the surgically removed nasal mucosa tissues of both nAR and AR groups. Significantly higher Ras activation was detected in AR Eos than that in nAR Eos. Ras activation was associated with the apoptosis resistance in AR Eos. The Twist (an apoptosis inhibitor) expression was higher in AR Eos, which was positively correlated with the Ras activation status. The sensitization to IgG induced Twist expression in Eos, in which Ras activated the MAPK-HIF-1α pathway, the latter promoted the Twist gene transcription. Twist bound Rac GTPase activating protein-1 to sustain the Ras activation in Eos. Ras activation sustained the apoptosis resistance in Eos. In conclusion, high Ras activation was detected in the AR nasal mucosal tissue-isolated Eos. IgG-sensitization induced Ras activation and Twist expression in Eos, that conferred Eos the apoptosis resistance.

Specific antigen-guiding exosomes inhibit food allergies by inducing regulatory T cells.

The therapies for food allergy (FA) need to be improved. The generation of inducible regulatory T cells (Tregs) can support immune tolerance in the body. This study aims to suppress experimental FA by inducing Tregs through the employment of modified exosomes (mExosomes). In this study, mExosomes were prepared by incubating dendritic cells with interleukin (IL)-2 and ovalbumin (OVA, used as a specific antigen) in the culture. Exosomes were purified from culture supernatant and used as the mExosomes. A murine FA model was developed to test the effects of mExosomes on the generation of Tregs in the mouse intestinal tissues and inhibiting FA. The results showed that mExosomes, which carried IL-2 and a complex of OVA peptide-major histocompatibility complex class II on the surface of exosomes, bound to OVA-specific CD4+ T cells and induced CD4+ T cells to differentiate into Tregs. In the FA mouse intestinal tissues, we found low IL-2 levels that were positively correlated with the number of Tregs. Depletion of IL-2 in mice prevented the generation of Tregs. The levels of peroxisome proliferator-activated receptor-γ were increased in the FA intestinal tissues with inhibited IL-2 production. Administration of mExosomes induced Tregs in the intestinal tissues and efficiently suppressed FA in mice. We conclude that the mExosomes can suppress FA in mice through inducing Tregs. The data suggest that the mExosomes have translational potential in the treatment of FA and other allergic disorders.

Mal-deficiency impairs the tolerogenicity of dendritic cell of patients with allergic rhinitis.

The tolerogenic dendritic cell dysfunction is associated with the pathogenesis of immune diseases. Microbial stimulus is required in the maintenance of immune functions. This study aims to elucidate the role of Mal signal in the maintenance of DEC205+ DC (decDC) immune tolerogenic function. In this study, peripheral DCs were collected from allergic rhinitis (AR) patients and healthy control (HC) subjects to assess the functional status of decDCs. An AR murine model was developed to test the role of Mal signals in the maintenance of decDCs' functions. We observed that AR decDCs (decDCs obtained from AR patients) were incompetent in the induction of type 1 regulatory T cells (Tr1 cells). AR decDCs expressed less IL-10 than that in HC decDCs. IL-10 mRNA decayed spontaneously in AR decDCs. Tat-activating regulatory DNA-binding protein-43 (TDP43) protected IL-10 mRNA from decay. AR decDCs expressed lower levels of Mal than that in HC decDCs. Mal depletion resulted in IL-10 mRNA decay in HC decDCs. Reconstitution of Mal in AR decDCs restored the capacity of inducing Tr1 cells and attenuated experimental AR in mice. In conclusion, Mal plays a critical role in the maintenance of decDC's immune tolerogenic function. The absence or insufficient Mal signal impairs decDC's tolerogenic property. Reconstitution of Mal in AR decDCs can restore the immune tolerogenic capacity, which may have translational potential in the treatment of AR and other allergic diseases.

Impact of metabolic syndrome on recovery of idiopathic sudden sensorineural hearing loss.

PURPOSE: Metabolic syndrome (MetS) was reported to a risk factor of developing idiopathic sudden sensorineural hearing loss (ISSNHL), but limited data exist on its effect on the recovery. The purpose of this study was to evaluate the impact of (MetS) and its components on recovery of patients with ISSNHL. MATERIAL AND METHODS: 228 ISSNHL patients were divided into MetS group and Non-MetS group according to the diagnostic criteria of MetS, and demographic and clinical characteristics and hearing recovery were reviewed between two groups. RESULTS: In total, 86 (37.7%) patients in MetS group, and 142 (62.3%) patients in Non-MetS group. The rate of hypertension, diabetes mellitus, low HDL-C, high TG and obesity were significantly higher in the MetS group than those in the Non-MetS group (P < 0.05). The complete recovery rate and partial recovery rate were significantly lower in the MetS group than those in the Non-MetS group. According to the multivariate analysis, MetS was significantly associated with a poor prognosis; high initial hearing threshold and presence of diabetes mellitus were correlated with a poor prognosis (P < 0.05). CONCLUSIONS: These results suggest that MetS has a negative impact on the hearing recovery of ISSNHL. High initial hearing threshold and diabetes mellitus were indictors of a poor prognosis of ISSNHL.

miR-1, regulated by LMP1, suppresses tumour growth and metastasis by targeting K-ras in nasopharyngeal carcinoma.

There is evidence to show that downregulation of miR-1 expression is closely related to cancer progression, including in nasopharyngeal carcinoma (NPC). However, the molecular mechanisms underlying miR-1 downregulation in NPC remain largely unknown, especially its association with Epstein-Barr virus (EBV). In this study we found that restoration of miR-1 dramatically inhibited cell invasion in vitro, together with tumour growth and metastasis in vivo. Importantly, we found that LMP1, an Epstein-Barr virus (EBV)-associated protein, suppressed miR-1 expression. Furthermore, we identified K-ras as a novel direct target of miR-1. Our results demonstrated for the first time that miR-1 was suppressed by LMP1 and its tumour-suppressive effects were mediated chiefly by repressing K-ras expression. We propose that miR-1 could serve as an independent biomarker to identify patients with different clinical characteristics.

Enhanced thermoelectric properties of Ga-doped In2O3 ceramics via synergistic band gap engineering and phonon suppression.

Ga doped In2O3-based thermoelectric materials were prepared by spark plasma sintering (SPS) using sintered powders in the low temperature solid phase. The solubility of Ga in In2O3 is about 10 at%, much larger than other elements such as Ge, Ce, etc. The larger solubility of Ga allows us to optimize the thermal and electrical transport properties of Ga doped In2O3 in a wider window. While tuning the concentration of dopants, the thermoelectric performance of Ga doped In2O3 was enhanced through a synergistic approach combining band-gap engineering and phonon suppression. The power factor increases from ∼0.5 × 10(-4) to ∼9.6 × 10(-4) W mK(-2) at 700 °C while thermal conductivity reduces from ∼4 to ∼2 W mK(-1) at 700 °C in In1.9Ga0.1O3. The maximum ZT of 0.37, increased by a factor of 4 from the pristine In2O3, is achieved in In1.9Ga0.1O3 at 700 °C.

Application of bidirectional telemedicine in home CPAP for children with obstructive sleep apnea syndrome.

BACKGROUND: Traditional telemedicine follow-up proves unsuitable for home continuous positive airway pressure (CPAP) therapy in children with obstructive sleep apnea syndrome (OSAS). Accompanying advancements in mobile internet, this study explores the feasibility and effectiveness of a mobile communication and remote monitoring system as a novel bidirectional telemedicine approach to enhance adherence to home CPAP in children with OSAS. METHODS: A prospective cohort utilizing bidirectional telemedicine follow-up from January to December 2022 (TM) was compared with a retrospective cohort receiving conventional phone follow-up from August 2018 to December 2021 (CP). Participants in TM group were subdivided into two groups based on the number of inquiries in the first week: a high-question group and a low-question group. The main endpoints included successful CPAP adaption and adherence at 2 months of follow-up. RESULTS: The TM group exhibited a significantly lower termination rate within 2 months compared to the CP group (1/24 vs. 6/22, p = 0.037). In the first week of home CPAP, the high-question group reported shorter average nightly usage and fewer days with usage of ≥4 h compared to the low-question group (5 h per night vs. 8.5 h per night, 4.5 days vs. 7 days, both p < 0.001). However, the high-question group showed significant improvement in adherence from the second week onward for the remainder of the study period. CONCLUSIONS: Bidirectional telemedicine represents an effective and feasible method to improve adherence to home CPAP therapy in children with OSAS. Considering the costs, researchers recommend applying bidirectional telemedicine for at least 1 week to better enhance long-term adherence.

TRIM41 contributes to the pathogenesis of airway allergy by compromising dendritic cells' tolerogenic properties.

Dendritic cells (DC) play a crucial role in the initiation of immune responses. TRIM41, an E3 ubiquitin ligase, can facilitate targeting protein degradation. The purpose of this study is to analyze the role of TRIM41 in the pathogenesis of airway allergy (AA) and the impact of regulating TRIM41 on suppressing AA. We observed that the airway DCs of AA mice had a higher expression of Trim41. The expression of Trim41 in airway DCs was associated with the DCs' tolerogenic functions of AA mice. The AA responses, including increased amounts of eosinophil peroxidase, mast cell protease-1, Th2 cytokines, and specific IgE in bronchoalveolar lavage fluids, were positively correlated with the Trim41 expression in mouse airway DCs. TRIM41 induced c-Maf degradation and interfered with the Il10 expression in airway DCs, which could be counteracted by inhibiting TRIM41. Regulation of TRIM41 mitigated experimental AA responses.

[Prediction of hemorrhage rate after tonsil surgery in children based on random forest model].

Objective:Hemorrhage after tonsil surgery in children is a serious and potentially life-threatening complication. The purpose of this study was to establish a risk warning model for hemorrhage after tonsil surgery in children through a national multi-center retrospective study, providing a basis for hierarchical management after tonsil surgery in children. Methods:Stratified sampling was performed on 8 854 children who underwent tonsillectomy under general anesthesia from 15 research centers in different provinces from January 15, 2022 to May 15, 2023. The sample size of this study was 2 724 cases, including 1 096 males and 1 628 females. Children were divided into bleeding and non-bleeding groups according to whether or not they had bleeding after surgery. The random forest algorithm was used to build a risk warning model. By continuously exploring the optimized model, the accuracy of predicting the postoperative bleeding rate of tonsils in children was improved, and the prediction effectiveness of the model was verified by ten-fold cross-validation. Results:Among 2 724 children, 117 had postoperative bleeding after tonsillectomy, with a bleeding rate of 4.30%. The model constructed by the random forest algorithm for the training set was verified in the test set, and the obtained prediction accuracy was 98.72%, the recall rate was 78.95%, and the area under the ROC curve AUC was 0.96. Conclusion:Although the recall rate of the random forest model needs to be improved, the overall accuracy is quite excellent. It can effectively avoid misjudging positive cases as negative cases. It is a useful tool that can be used to predict the postoperative bleeding rate of tonsils and clinical medical decision-making, laying a good foundation for subsequent optimization and improvement.

Nano-inclusions: a novel approach to tune the thermal conductivity of In2O3.

Indium oxides such as In2O3 based thermoelectric ceramics exhibit a figure of merit ZT ~0.5 above 1000 K, while optimized ZnO based thermoelectrics may reach ZT ~0.3 at 1273 K. A way to further optimize the thermoelectric performance is to tune the thermal conductivity. In this work, a reduction of the thermal conductivity greater than 30% has been observed. Combining thermal conductivity measurements, Scanning Electron Microscopy (SEM) images, X-ray Absorption Fine-structure spectroscopy (XAFS) data and Full Multiple Scattering calculations, we associated the phenomenon with an effective scattering of mid- and long-wavelength phonons by embedded ZnO nano-inclusions in the In2O3 matrix. The results suggest a protocol for the synthesis of new heat-designed materials for many novel applications, such as high ZT thermoelectrics, thermal crystals, heat optics devices, etc.

[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.

[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.

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.

[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.

[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.