RUNX1-BMP2 promotes vasculogenic mimicry in laryngeal squamous cell carcinoma via activation of the PI3K-AKT signaling pathway.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is one of the most common malignant tumors of the head and neck. Vasculogenic mimicry (VM) is crucial for tumor growth and metastasis and refers to the formation of fluid channels by invasive tumor cells rather than endothelial cells. However, the regulatory mechanisms underlying VM during the malignant progression of LSCC remain largely unknown. METHODS: Gene expression and clinical data for LSCC were obtained from the TCGA and Gene GEO (GSE27020) databases. A risk prediction model associated with VM was established using LASSO and Cox regression analyses. Based on their risk scores, patients with LSCC were categorized into high- and low-risk groups. The disparities in immune infiltration, tumor mutational burden (TMB), and functional enrichment between these two groups were examined. The core genes in LSCC were identified using the machine learning (SVM-RFE) and WGCNA algorithms. Subsequently, the involvement of bone morphogenetic protein 2 (BMP2) in VM and metastasis was investigated both in vitro and in vivo. To elucidate the downstream signaling pathways regulated by BMP2, western blotting was performed. Additionally, ChIP experiments were employed to identify the key transcription factors responsible for modulating the expression of BMP2. RESULTS: We established a new precise prognostic model for LSCC related to VM based on three genes: BMP2, EPO, and AGPS. The ROC curves from both TCGA and GSE27020 validation cohorts demonstrated precision survival prediction capabilities, with the nomogram showing some net clinical benefit. Multiple algorithm analyses indicated BMP2 as a potential core gene. Further experiments suggested that BMP2 promotes VM and metastasis in LSCC. The malignant progression of LSCC is promoted by BMP2 via the activation of the PI3K-AKT signaling pathway, with the high expression of BMP2 in LSCC resulting from its transcriptional activation by runt-related transcription factor 1 (RUNX1). CONCLUSION: BMP2 predicts poor prognosis in LSCC, promotes LSCC VM and metastasis through the PI3K-AKT signaling pathway, and is transcriptionally regulated by RUNX1. BMP2 may be a novel, precise, diagnostic, and therapeutic biomarker of LSCC.

[Analysis of clinical manifestations and imaging features of facial nerve schwannomas].

Objective:To explore the clinical manifestations and imaging characteristics, and to clarify the imaging value in the diagnosis of facial nerve schwannomas. Methods:Retrospectively analyze the data of 23 patients with facial nerve schwannomas confirmed by surgery and pathology in the Department of Otorhinolaryngology of the First Affiliated Hospital of the Air Force Military Medical University from September 2020 to September 2022, including 8 males and 15 females, aged 18-66 years old. Summarize and analyze their clinical symptoms, specialized examinations, and imaging findings. Results:The clinical manifestations were facial nerve paralysis in 15 cases（2 cases of HB Ⅳ, 6 cases of HB Ⅴ, 7 cases of HB Ⅵ）, hearing loss in 14 cases（5 cases of conductive deafness, 2 cases of mixed deafness, and 7 cases of severe sensorineural hearing loss）, 8 cases tinnitus, 7 cases ear pain, 4 cases dizziness, 4 cases headache, 2 cases ear pus, and parotid gland tumors in 6 cases presenting as local masses. Endoscopic examination revealed 8 cases of external ear canal tumors and 3 cases of intratympanic tumors. Combining temporal bone HRCT, MRI enhanced scanning, and CPR imaging techniques, 1 case involved the internal auditory canal segment, 2 cases in the tympanic segment, 6 cases in the parotid gland area. A total of 14 cases involved two or more segments of the internal auditory canal segment, the labyrinthine segment, geniculate ganglion, the tympanic segment, and the mastoid segment. When the tumors were large, adjacent structures were involved. It was found that 8 cases invaded the external auditory canal and tympanic cavity, ossicles were displaced or bony destruction; 3 cases invaded the jugular foramen area, and 1 case grew to the middle cranial fossa region with temporal lobe brain parenchymal compression. Conclusion:The clinical manifestations of facial nerve schwannomas are diverse. The combination of various imaging techniques will be conducive to topical and qualitative diagnosis and provide an important basis for treatment strategies.

Choanal Polyps With Osseous Metaplasia From the Nasal Septum: A Case Report and the Literature Review.

Choanal polyps belong to a special type of nasal polyps, which are quite uncommon if originating from the nasal septum, especially those with osseous metaplasia. In this article, we report the case of a 63-year-old male patient with persistent nasal obstruction on the right side. An irregular light yellow lobulated mass with smooth surface could be visualized in the nasal cavity through nasal endoscopy, arising from the right nasal septum and extending to the nasopharynx. Computed tomography scan showed a large soft tissue shadow of the nasal meatus, with ossified structure in the center. Histopathological biopsy revealed nasopharyngeal mucositis. The patient underwent functional endoscopic sinus surgery and the polypoidal mass sent for histopathological examination proved to be choanal polyps.

Translocation of telomerase reverse transcriptase coincided with ATP release in postnatal cochlear supporting cells.

The spontaneous bursts of electrical activity in the developing auditory system are derived from the periodic release of adenosine triphosphate (ATP) by supporting cells in the Kölliker's organ. However, the mechanisms responsible for initiating spontaneous ATP release have not been determined. Our previous study revealed that telomerase reverse transcriptase (TERT) is expressed in the basilar membrane during the first postnatal week. Its role in cochlear development remains unclear. In this study, we investigated the expression and role of TERT in postnatal cochlea supporting cells. Our results revealed that in postnatal cochlear Kölliker's organ supporting cells, TERT shifts from the nucleus into the cytoplasm over time. We found that the TERT translocation tendency in postnatal cochlear supporting cells in vitro coincided with that observed in vivo. Further analysis showed that TERT in the cytoplasm was mainly located in mitochondria in the absence of oxidative stress or apoptosis, suggesting that TERT in mitochondria plays roles other than antioxidant or anti-apoptotic functions. We observed increased ATP synthesis, release and activation of purine signaling systems in supporting cells during the first 10 postnatal days. The phenomenon that TERT translocation coincided with changes in ATP synthesis, release and activation of the purine signaling system in postnatal cochlear supporting cells suggested that TERT may be involved in regulating ATP release and activation of the purine signaling system. Our study provides a new research direction for exploring the spontaneous electrical activity of the cochlea during the early postnatal period.

Cuproptosis-related LINC02454 as a biomarker for laryngeal squamous cell carcinoma based on a novel risk model and in vitro and in vivo analyses.

PURPOSE: Laryngeal squamous cell carcinomas (LSCCs) are aggressive tumors with the second-highest morbidity rate in patients with head and neck squamous cell carcinoma. Cuproptosis is a type of programmed cell death that impacts tumor malignancy and progression. The purpose of this study was to investigate the relationship between cuproptosis-related long non-coding RNAs (crlncRNAs) and the tumor immune microenvironment and chemotherapeutic drug sensitivity in LSCC, and crlncRNA impact on LSCC malignancy. MATERIALS AND METHODS: Clinical and RNA-sequencing data from patients with LSCC were retrieved from the Cancer Genome Atlas. Differentially expressed prognosis-related crlncRNAs were identified based on univariate Cox regression analysis, a crlncRNA signature for LSCC was developed and validated using LASSO Cox regression. Finally, the effect of LINC02454, the core signature crlncRNA, on LSCC malignancy progression was evaluated in vitro and in vivo. RESULTS: We identified a four-crlncRNA signature (LINC02454, AC026310.1, AC090517.2, and AC000123.1), according to which we divided the patients into high- and low-risk groups. The crlncRNA signature risk score was an independent prognostic indicator for overall and progression-free survival, and displayed high predictive accuracy. Patients with a higher abundance of infiltrating dendritic cells, M0 macrophages, and neutrophils had worse prognoses and those in the high-risk group were highly sensitive to multiple chemotherapeutic drugs. Knockdown of LINC02454 caused tumor suppression, via cuproptosis induction. CONCLUSIONS: A novel signature of four crlncRNAs was found to be highly accurate as a risk prediction model for patients with LSCC and to have potential for improving the diagnosis, prognosis, and treatment of LSCC.

Comparative Analysis of the Hearing Effects of Partial Ossicular Replacement Prosthesis Versus Conchal Cartilage in Canal Wall Down Mastoidectomy with Type II Tympanoplasty: A Retrospective Case Review Study.

OBJECTIVES: To investigate the effects of titanium partial ossicular replacement prosthesis (PORP) and conchal cartilage for ossiculoplasty on hearing results in single-stage canal wall down (CWD) mastoidectomy surgery with type II tympanoplasty in patients with cholesteatoma. METHODS: The patients were performed surgeries for the first time by a senior otosurgeon from 2009 to 2022 and were performed CWD mastoidectomy with type II tympanoplasty in one stage were enrolled. Patients who could not be followed up were excluded. Titanium PORP or conchal cartilage was used for ossiculoplasty. When the stapes head was intact, a cartilage 1.2-1.5 mm thick was attached directly to the stapes; when the head of the stapes was eroded, a 1 mm high PORP and cartilage of .2-.5 mm thick were placed on the stapes simultaneously. RESULTS: 148 patients were included in the study in total. The titanium PORP and conchal cartilage groups showed no statistically significant differences at 500, 1000, 2000, and 4000 Hz considering the number of decibels of closure of the air-bone gap (ABG) (P > .05) and pure-tone average ABG (PTA-ABG) (P > .05). Meanwhile, the closure of PTA-ABG between the 2 groups showed no statistically significant differences in the overall distribution (P > .05). CONCLUSIONS: For patients with cholesteatoma and mobile stapes who underwent CWD mastoidectomy with type II tympanoplasty in one stage, either PORP or conchal cartilage is a satisfactory material for ossiculoplasty.

NRG1/ErbB2 axis regulated mitochondrial function and antioxidant enzymes of neural stem cells in the cochlear nucleus partially through PGC-1α.

Neuregulin-1 (NRG1)/erythroblastic leukaemia viral oncogene homologues 2 (ErbB2) pathway had been implicated in promoting differentiation and suppressing apoptosis of neuronal stem cells (NSCs) isolated from cochlear nucleus. In the current study, we aimed at determining the effects of NRG1/ErbB2 on mitochondrial (mt) function of NSCs. As expected, NRG1 increased the expression of mitofusin (Mfn) 1 and Mfn2 and decreased the expression of mitochondrial fission protein 1 (Fis1) and dynamin-related protein 1 (Drp1). However, after ErbB2 knockout, Mfn1 and Mfn2 expression decreased while Fis1 and Drp1 increased. Moreover, the increased mtDNA copy number and intracellular ATP level, elevated ATPase activities as well as decreased lactate production induced by NRG1 were partially reversed by ErbB2 knockout. Additionally, NRG1 treatment increased the activities of catalase, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and upregulated the protein expression of catalase, manganese superoxide dismutase (MnSOD), peroxisome proliferator-activated receptor-γ coactlvator-1α (PGC-1α), nuclear respiratory factor 1 (NRF1) and transcription factor A, mitochondrial (TFAM), which were also reversed by ErbB2 knockout. Furthermore, PGC-1α overexpression partially reversed the above effects of ErbB2 knockout. In conclusion, these findings suggest that the promotion of mitochondrial function of NRG1/ErbB2 axis is at least in part mediated by PGC-1α in NSCs from cochlear nucleus.

[Clinical features, diagnosis and treatment for patients presenting with granulation tissue of the external auditory canal].

Objective:To explore the clinical characteristics and diagnosis and treatment in the patients presenting with granulation tissue of the external auditory canal. Methods:The data of 71 postoperative patients presenting with granulation tissue of the external auditory canal in the Department of Otolaryngology, the First Affiliated Hospital of the Air Force Military Medical University from January 2015 to June 2020 were analyzed retrospectively, including the chief complaint, physical examination, auxiliary examination and preoperative imaging, biopsy was performed when necessary to confirm the diagnosis. Among the 71 patients, 30 cases were diagnosed as chronic otitis media, 19 cases were external auditory canal cholesteatoma, 5 cases were external auditory canal carcinoma, 6 cases were paraganglioma, 1 case was granulomatous hemangioma, 1 case was first branchial cleft fistula, 4 cases were granuloma of the external auditory canal, 4 cases were hemangioma of the external auditory canal, and 1 case was foreign body of the external auditory canal. Individualized treatment plans are made according to the characteristics and extent of the lesions. Results:Postoperative follow-up was 12 to 74 months, with an average of （44±18.1） months. Seventy patients（98.6%） had no complications such as sensorineural deafness, external auditory stenosis or peripheral facial paralysis after surgery, and one patient with paraganglioma had postoperative neurological function grade Ⅱ, and was treated with nutritional nerves, and the postoperative neural function recovered to grade Ⅰ after 3 months. Conclusion:The patients presenting with granulation tissue of the external auditory canal can be diagnosed as various diseases. It is necessary to analyze the patient's medical history in detail, confirm the diagnosis in combination with imaging examination, and formulate an individualized treatment plan to reduce misdiagnosis and missed diagnosis.

A forskolin-loaded nanodelivery system prevents noise-induced hearing loss.

Hearing loss is the most common sensory disorder worldwide and may result from age, drugs, or exposure to excessive noise. Crossing the blood-labyrinth barrier to achieve targeted drug delivery to the inner ear is key to the treatment of hearing loss. We designed a nanoparticle (NP)-based system for targeted drug delivery of forskolin (FSK) to the inner ear, driven by the prestin-targeting peptide LS19 ("ligand-receptor type interaction"). In vivo experiments in developing zebrafish embryos (4-96 h past fertilization) and mice confirmed that LS19-FSK specifically targeted and accumulated in zebrafish lateral line neuromasts and mouse outer hair cells (OHCs). LS19 peptide modification enabled LS19-FSK-NPs to rapidly target OHCs with high specificity. Furthermore, the multifunctional LS19-FSK-NPs were successfully delivered to the OHCs via the round window membrane route and exhibited slow-release properties. The sustained release and intracellular accumulation of FSK inhibited apoptosis of OHCs. Compared with LS19-NPs and FSK-NPs, LS19-FSK-NPs provided significantly stronger protection against noise-induced hearing damage, based on auditory brainstem responses at 4, 8, 16, and 32 kHz. Thus, our specially designed targeted nano-delivery system may serve as a basis for future clinical applications and treatment platforms and has the potential to significantly improve the treatment results of many inner ear diseases.

[Perioperative management of cochlear implantation for CHARGE syndrome].

Objective:To explore the perioperative period characteristics of paediatric cochlear implant recipients of CHARGE syndrome with complex deformities. Methods:Retrospective case series of CHARGE syndrome were included. Radiological results, intraoperative findings, surgical planning and post-operative complications were analyzed. Routine audiometric measurements, speech perception categories and speech intelligibility ratings were performed pre and post-operatively to measure auditory speech rehabilitation outcomes. Results:Five prelingual profoundly deaf children were identified, aged from 14 months to 60 months. All patients had congenital heart disease and underwent surgery before cochlear implantation. Upper airway abnormalities were detected as choanal atresia, laryngomalacia and tracheal stenosis. All ten ears showed cochlear abnormalities（Incomplete partition Ⅱ）, eight of them combined with secretory otitis media and/or middle ear deformity. All patients underwent single side surgery using standard transmastoid facial recess approach. Full insertion of the electrode was achieved in two cochleas, while partial insertion was done in three cochleas. Three ears with absent auditory nerves in MRI showed no response in the neural remote test. All patients had improved audio-speech performance with CAP scores 3.0±0.7 and 3.6±0.9, SIR scores 1.2±0.4 and 1.8±0.8, IT-MAIS scores 18.8±9.1 and 26.2±10.0, MUSS scores 2.2±2.4 and 7.2±8.3 after twelve months and twenty-four months follow up. Conclusion:Cochlear implantation in patients with CHARGE syndrome is a challenge in both its surgical and rehabilitation aspects due to multiple abnormalities. Adequate treatment planning is necessary for safe and effective surgery, including airway structures and intricate temporal bone landmarks.

De novo Splice Site Mutation of the CHD7 Gene in a Chinese Patient with Typical CHARGE Syndrome.

INTRODUCTION: CHARGE syndrome (CS, OMIM 214800) is a rare genetic disease characterized by multiple congenital abnormalities, including coloboma, heart defect, atresia of the choanae, retardation of development, genital anomalies, and ear anomalies/deafness. The syndrome is mainly caused by a heterozygous variant in the chromodomain helicase DNA-binding protein 7 (CHD7) gene that encodes the CHD7 protein, involved in the ATP-dependent remodeling of chromatin. METHODS: In this study, the next-generation sequencing targeted panel was used to detect a de novo variant c.3523-2A>G in the CHD7 gene in a patient with severe CS, congenital heart disease, left coloboma of the choroid, cryptorchidism, and congenital deafness. The Sanger sequencing confirmed the variant and clarified it as de novo variant by short tandem repeat analysis in the patient family. We analyzed the effect of a variant by Minigene assay to evaluate the pathogenicity of the variant. RESULTS: In summary, cDNA analysis confirmed that c.3523-2A>G variant activates a cryptic splice site, resulting in 172 base pair missing in exon 15, leading to the premature truncation of the CHD7 protein (p.V1175Afs*11). CONCLUSION: The present study functionally characterized the novel c.3523-2A>G variant in CHD7, providing further confirmatory evidence that it is associated with CS.

Analysis of the Clinical Features and Surgical Outcomes of First Branchial Cleft Anomalies.

OBJECTIVES: To analyze the clinical features and otologic manifestations of first branchial cleft anomalies (FBCAs) and the disparity between Work's classification, and to explore the relationships between postoperative facial paralysis and features of FBCAs. STUDY DESIGN: Retrospective clinical study. METHODS: A retrospective analysis of 109 patients with FBCAs was conducted, including clinical characteristics and otologic features. Pearson chi-square tests and Fisher's exact tests were used to compare disparity between Work's classification, and the impact factors of postoperative facial paralysis among 86 patients who were explored in follow-up. RESULTS: Patients with FBCAs presented with otologic symptoms, including cysts or fistula in the external auditory canal (EAC) and periauricular (43.2%), microtia (3.7%), EAC web (1.8%), otitis media (1.8%), and otorrhea (4.6%). Eighty-five cases (78.0%) were type I FBCAs and 24 (22.0%) were type II. Compared to type I FBCAs, type II (58.3%) was more likely to be located deep to the facial nerve (FN) and to have superficial parotidectomy on them (79.2%). This difference was statistically significant (P < .001). FBCAs deep to the FN had a higher incidence of postoperative facial paralysis (P < .05). CONCLUSION: The majority of patients (55.0%) had otologic symptoms. The FBCAs of Work type II was commonly deep to the FN and superficial parotidectomy was frequently performed. Postoperative facial paralysis was associated with FBCAs located deep to the FN, but not with Work's type. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:1008-1014, 2022.

[Clinical features and prognostic factors for early-stage external auditory canal carcinoma].

Objective:To analyze the clinical features and the prognostic factors of early-stage external auditory canal carcinoma. Methods:Data from 36 patients with early-stage external auditory canal carcinoma（T1, T2） treated in Department of Otolaryngology, Xijing Hospital, Air Force Military Medical University from January 2008 to June 2020 were reviewed retrospectively, including clinical manifestations, surgical and treatment methods, pathological types and disease status. The relationship between survival rate and the prognostic factors was compared using Kaplan-Meier method, and the independent risk factors were analyzed by Cox proportional hazards model. Results:There were 36 patents with early-stage external auditory canal carcinoma. The common initial symptoms were otalgia（66.7%）, otorrhea（41.7%） and hearing loss（30.6%）. The most common histopathologic types were adenoid cystic carcinoma（50.0%） and squamous cell carcinoma（33.3%）. Among the patients, 21 patients（58.3%） were initially treated, 9 patients（25.0%） were treated with salvage therapy, and 6 patients（16.7%） were re-surgery after recurrence. The 5-year disease-specific survival（DSS）, disease-free survival（DFS） and relapse-free survival（RFS） were 82.3%, 64.0% and 73.0% respectively. Seven cases （19.4%） relapsed after surgery. For 5-year survival rate, the lateral temporal bone resection with superficial parotidectomy（DSS 91.7%, DFS 83.9%） is higher than the lateral temporal bone resection only（DSS 77.8%, DFS 55.6%） and sleeve resection（DSS 75.0%, DFS 56.0%）, but there was no significant difference（P>0.05）. In these patients, the postoperative radiotherapy and disease status had no significant impact on the survival rate. Additionally, there was no obvious correlation between recurrence and age, gender, stage, histopathologic types, operation methods and postoperative radiotherapy（P>0.05）. But there were significant differences between histopathologic types and DSS or DFS（P<0.05）. Multivariate regression analysis showed that histopathologic type was an independent prognostic factor for DFS. Conclusion:There are no specific clinical manifestations for early-stage external auditory canal carcinoma, such as otalgia and otorrhea. Histopathologic types have a direct impact on the patients'prognosis. Thus, individualized treatment should be applied based on pathologic findings to improve the survival rate.

Unusual presentation of a first branchial arch fistula with maxillofacial infection: a case report.

BACKGROUND: First branchial cleft anomaly (FBCA) is a rare congenital defect that arises due to incomplete closure of the ventral portion of the first and second branchial arches. There are variable complex clinical manifestations for patients with FBCA, which are prone to misdiagnosis and inadequate treatment. FBCAs usually involve the facial nerve with a consequent increased risk of facial nerve damage. Here, we present an unusual case of FBCA presenting with two preauricular pits in association with an abnormal maxillofacial cyst. CASE PRESENTATION: A 10-month-old girl presented to our department due to recurrent maxillofacial infections accompanied by swelling or abscess of the left cheek and purulent discharge from the preauricular pit for 4 months. A 3D-computed tomography (CT) fistulogram and magnetic resonance imaging (MRI) revealed two conjunctive tract lesions: one tract arose from the skin surface anteroinferior to the external auditory canal (EAC), through the deep lobe of the left parotid, and anteriorly extended to the left masseter; the other extended from the superficial lobe of the left parotid to the intertragic notch. After the maxillofacial infection was controlled by intravenous antibiotic administration, surgery was performed. Intraoperative tools, such as facial nerve monitors, microscopes, and methylene blue dyes, were used to facilitate the complete dissection and protection of the facial nerve. On follow-up over one year, the patient recovered well without facial palsy or recurrence. CONCLUSION: FBCA with maxillofacial cysts is rare and prone to misdiagnosis. Physicians should pay attention to this anatomic variant of FBCA with the fistula track located deep inside the facial nerve and projected medially to the masseter.

[Analysis of clinical effect of nasal endoscope-assisted nasal columella approach for simultaneous correction of nasal septum deviation and crooked nose deformity].

Objective:To analyze the clinical effect of nasal endoscope-assisted nasal columella approach in the correction of nasal septum deviation and crooked nose deformity. Methods:The clinical data of 33 patients with deviation of nasal septum with crooked nose deformity in First Affiliate Hospital of Air Force Military Medical University from January 2016 to June 2019 were collected. All patients underwent surgery under general anesthesia. Nasal columella inverted "V" incision was used to expose and release. The deviated nasal septum cartilage and bone were removed with the assistance of nasal endoscope. Twelve（36.4%） patients underwent osteotomy of nasal bone and frontal process of maxilla at the same time, 13（39.4%） patients used autologous nasal septum to reshape the tip, back and external nose. Results:During a follow-up of 18 months to 60 months, 30（90.9%） patients were satisfied with the improvement of postoperative nasal function, 3（9.1%） patients were basically satisfied; 23（69.7%） patients were satisfied with the appearance of the nose after operation, 8（24.2%） patients were basically satisfied, and 2（6.1%） patients were dissatisfied. No postoperative complications such as nasal adhesion, nasal septum perforation, nasal septum hematoma and nasal dorsal collapse occurred in all patients. Conclusion:The nasal endoscope-assisted nasal columella approach and the correction of nasal septum deviation and crooked nose deformity can solve the nasal deformity and nasal ventilation function at the same time, realize the unity of cosmetology and function, and reduce the frequency and cost of surgical treatment at the same time. The effect is good, and the patients benefit greatly.

A novel KCNQ4 gene variant (c.857A>G; p.Tyr286Cys) in an extended family with non­syndromic deafness 2A.

Deafness is one of the most common sensory disorders found in humans; notably, >60% of all cases of deafness have been attributed to genetic factors. Variants in potassium voltage­gated channel subfamily Q member 4 (KCNQ4) are etiologically linked to a type of progressive hearing loss, deafness non­syndromic autosomal dominant 2A (DFNA2A). In the present study, whole­exome sequencing (WES) was performed on three members of a five­generation Chinese family with 46 members with hearing loss. Pure tone audiometry and Sanger sequencing were performed for 11 family members to determine whether the novel variant in the KCNQ4 gene was segregated with the affected family members. In addition, evolutionary conservation analysis and computational tertiary structure protein prediction of the wild­type KCNQ4 protein and its variant were performed. The family exhibited autosomal dominant, progressive, post­lingual, non­syndromic sensorineural hearing loss. A novel co­segregating heterozygous missense variant (c.857A>G; p.Tyr286Cys) in the glycine­tyrosine­glycine signature sequence in the pore region of the KCNQ4 channel was identified. This variant was predicted to result in a tyrosine­to­cysteine substitution at position 286 in the KCNQ4 protein. The tyrosine at position 286 is well conserved across different species. The substitution of tyrosine with cysteine would affect the structure of the pore region, resulting in the loss of channel function. The KCNQ4 gene is one of the most common mutated genes observed in patients with autosomal dominant, non­syndromic hearing loss. Taken together, for the family analyzed in the present study, performing WES in conjunction with Sanger sequencing has led to the detection of a novel, potentially causative variant (c.857 A>G; p.Tyr286Cys) in exon 6 of the KCNQ4 gene. The present study has added to the number of pathogenic variants observed in the KCNQ4 gene, and the findings may prove to be useful for both the diagnosis of DFNA2A and in the design of early interventional therapies.

[Comparative analysis of the hearing of three type reconstruction material in type â ¡ tympanoplasty of 286 cases].

Objective:To compare the effect on hearing of different reconstruction material in type Ⅱ tympanoplasty. Methods:Retrospectively analysis of 286 patients who accepted type Ⅱ tympanoplasty. The air-bone gap of 0.5, 1, 2, 4 kHz was analyzed before and after operation. We compared the hearing change and the complications between each group. Results:In incus group, the manubrium mallei and the head of stapes were connected with shaped incus, PORP group were implanted with PORP during operation, and cartilage group used auricular cartilage to cover the head of stapes. There was no significant difference in 4 kHz air-bone gap（ABG） between the cartilage group and PORP group either before or after the operation （P>0.05）. Air-bone gap of 0.5, 1, 2, 4 kHz of the incus group, and the 0.5, 1, 2 kHz of the cartilage and PORP group were significantly reducedafter the operation（P<0.05）. One patient got severe sensorineural hearing loss in incus group after the operation. The high frequency of bone conduction decreased in 1 patient（2, 4 kHz）.In the incus group, 3 patients had temporary facial paralysis after operation. Incus and cartilage group each have 1 patient with dizziness after the operation. Incus, cartilage and PORP group had 5, 3 and 11 patients with perforation again respectively. There was extrusion occurred in 1 patient of PORP group. Conclusion:Self incus, cartilage and PORP can be used in typeⅡ tympanoplasty, the effect of hearing reconstruction is similar. The first two are more economical, PORP implantation has the lowest technical difficulty and the most widely application, but there is a certain risk of extrusion .

[Evaluation of clinical application of new remote radar monitoring equipment for obstructive sleep apnea].

Objective:The result consistency between the new remote radar monitoring equipment and PSG detection is compared. Methods:The monitoring results of 71 patients were randomly selected to observe and compare the difference of monitoring data of the same patient with two kinds of detection equipment. Results:Using AHI≥5 as the diagnostic criteria, compared with PSG monitoring results, the sensitivity, specificity and Youden index of the new remote radar monitoring equipment were 96.2%, 89.5% and 0.857（P<0.01） respectively. Compared with PSG monitoring results, when LSaO2≤90% in PSG monitoring, the sensitivity, specificity and Youden index of the new remote radar monitoring equipment were 94.3%, 88.9% and 0.832（P<0.01） respectively. Conclusion: There the new remote radar monitoring device can be used to monitor OSA.

Nrg1/ErbB2 regulates differentiation and apoptosis of neural stem cells in the cochlear nucleus through PI3K/Akt pathway.

Sensorineural hearing loss (SNHL) is a common causes of disability. Neural stem cells (NSCs) from the cochlear nuclei have been considered to be a potential direction for the treatment of SNHL. Neuregulin 1 (NRG1)/ErbB2 signaling displays an essential role in nervous system development. In this study, we aimed to explore the roles of NRG1/ErbB2 in differentiation and apoptosis of cochlear nuclei NSCs. The data showed that the expression of NGR1 and ErbB2 in cochlear nuclei NSCs isolated from rats were increased with the age of rats. NRG1 treatment reduced the nestin-positive cells number, increased the MAP2-positive and GFAP-positive cells number, decreased the expression of cleaved-caspase-3, and increased the activation of PI3K/AKT. ErbB2 knockdown by lentiviral-mediated ErbB2 shRNA infection reversed the effect of NRG1 on cochlear nuclei NSCs. LY294002 administration further enhanced the effect of ErbB2 silencing on the expression of nestin, MAP2, GFAP and cleaved-caspase-3. Taken together, NRG1/ErbB2 regulates differentiation and apoptosis of cochlear nucleus NSCs through PI3K/Akt pathway.

The regulatory role of SFRP5/WNT5A axis in allergic rhinitis through inhibiting JNK pathway activation and lowering mucin generation in human nasal epithelial cells.

Allergic rhinitis (AR) is tightly associated with type 2 inflammation. SFRP5 combined with WNT5A mainly inhibits chronic inflammatory response, atherosclerosis, and other metabolic disorders. However, the effect of SFRP5/WNT5A axis on recombinant human interleukin-13 (rhIL-13)-induced inflammation has not been studied. In this study, we aimed to investigate whether secreted frizzled-related protein 5 (SFRP5) could modulate the production of cytokines relevant to eosinophil infiltration and mucin secretion through blocking the activation of Wnt family 5A (WNT5A) signaling pathway. A mouse model of AR demonstrated low expression of SFRP5 and high expression of WNT5A, and indicated that the number of eosinophil and goblet cells was increased, concomitant with elevated IL-13, colony stimulating factor 2 (CSF2), chemokine ligand 11 (CCL11), Mucin 4, and Mucin 5AC levels. Furthermore, lentivirus-SFRP5 overexpression up-regulated the expression of SFRP5 but down-regulated WNT5A level, and inhibited the activation of JNK pathway via decreasing p-JNK1/2 (Thr183/Tyr185) and p-c-Jun (Ser73) protein expressions in rhIL-13-treated human nasal epithelial cells (HNEpCs). Noticeably, SFRP5 overexpression markedly reduced rhIL-13-induced inflammatory protein and mucin generation through lowered CSF2, CCL11, Mucin 4, as well as Mucin 5AC levels. Taken together, these findings confirmed the regulatory role of SFRP5/WNT5A axis in rhIL-13-mediated inflammatory response in HNEpCs.