A Pedigree Study of Hereditary Auditory Neuropathy with Optic Atrophy / 听力学及言语疾病杂志

Objective To investigate the genetic causes of auditory neuropathy with optic atrophy in a family.Methods The proband's medical history and family history were inquired in detail,and relevant clinical examina-tions were performed to confirm the diagnosis of auditory neuropathy with optic atrophy,and the genetic pedigree of the family was drawn.Peripheral blood of proband(Ⅲ-7)was collected for whole exome sequencing,and the patho-genicity of the detected mutations were interpreted.Blood samples of proband's wife(Ⅲ-8),eldest daughter(Ⅳ-7),second daughter(Ⅳ-9)and son(Ⅳ-10)were tested for mutation sites by Sanger sequencing.Combined with clinical manifestations and examination results,the family was studied.Results The genetic pattern of this family was autosomal dominant.The proband showed decreased visual acuity at the age of 19,bilateral sensorineural deaf-ness at the age of 30,and decreased speech recognition rate.Among 20 members of the family of 5 generations,10(2 deceased)showed similar symptoms of hearing and visual impairment.Proband(Ⅲ-7),eldest daughter(Ⅳ-7)and son(Ⅳ-10)underwent relevant examination.Pure tone audiometry showed bilateral sensorineural deafness.ABR showed no response bilaterally.The 40 Hz AERP showed no response in both ears.OAE showed responses in some or all of the frequencies.No stapedial reflex was detected.The eye movement of Ⅲ-7 and Ⅳ-10 were reasona-ble in all directions,and color vision was normal.Ocular papilla atrophy was observed in different degrees in fundus examination.OCT showed thinning of optic disc nerve fibers in both eyes,and visual evoked potential showed pro-longed P100 wave peak.They were diagnosed as hereditary auditory neuropathy with optic atrophy.A mutation of the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)at a pathogenic locus on chromosome 3 was detected by whole exon detection in Ⅲ-7.The results of generation sequencing analysis showed that the OPA1 gene c.1334G＞A(p.Arg445His,NM_015560.2)mutation of chromosome 3 was also found in Ⅳ-7 and Ⅳ-10.Meanwhile,the gen-otypes of Ⅲ-8 and Ⅳ-9 were wild homozygous,that is,no mutation occurred.Conclusion The OPA1 c.1334G＞A(p.Arg445His,NM_015560.2)mutation site might be the pathogenic mutation in this family.

CGRP inhibits proliferation, activation and cytokine secretion of group 2 innate lymphoid cells (ILC2) in peripheral blood from patients with allergic rhinitis / 细胞与分子免疫学杂志

Objective To investigate the effect of calcitonin gene-related peptide (CGRP) on the regulation of group 2 innate lymphoid cells (ILC2) in the peripheral blood of patients with allergic rhinitis (AR). Methods Peripheral blood mononuclear cells (PBMCs) were extracted from normal healthy individuals and AR patients, then stimulated with CGRP, interleukin 33 (IL-33) and CGRP combined with IL-33 for 3 days, with blank stimulus as control. The percentage of ILC2 in the four groups was measured by flow cytometry. After being sorted, ILC2 was given to CGRP, IL-33 and CGRP combined with IL-33 stimulation for 3 days, with blank stimulus as control. The percentage of IL-5 and IL-13 positive cells in ILC2 was detected by flow cytometry, and the levels of IL-5 and IL-13 in ILC2 supernatant were measured by ELISA. Results The percentage of ILC2 in the peripheral blood of AR patients was significantly higher than that of the control group. The levels of IL-5+ILC2 and IL-13+ILC2 were significantly increased by IL-33 single stimulation after culturing PBMCs. After adding IL-33 combined with CGRP stimulation, the levels of IL-5+ILC2 and IL-13+ILC2 in PBMCs were significantly reduced; after CGRP single stimulation, the levels of IL-5+ILC2 and IL-13+ILC2 in PBMCs were further decreased. After ILC2 was sorted and cultured, the levels of IL-5+ILC2 and IL-13+ILC2 showed significant increase after IL-33 single stimulation. The levels of IL-5+ILC2 and IL-13+ILC2 were decreased by IL-33 and CGRP co-stimulation, and they were further reduced after CGRP single stimulation. Compared to IL-33 single stimulation, IL-5 and IL-13 levels dropped significantly due to the IL-33 and CGRP co-stimulation. The levels of IL-5 and IL-13 were further reduced by CGRP single stimulation. Conclusion CGRP inhibits the proliferation and activation of peripheral blood ILC2 in AR and exert anti-inflammatory effects in AR.

Chinese Society of Allergy and Chinese Society of Otorhinolaryngology-Head and Neck Surgery Guideline for Chronic Rhinosinusitis

The current document is based on a consensus reached by a panel of experts from the Chinese Society of Allergy and the Chinese Society of Otorhinolaryngology-Head and Neck Surgery, Rhinology Group. Chronic rhinosinusitis (CRS) affects approximately 8% of Chinese adults. The inflammatory and remodeling mechanisms of CRS in the Chinese population differ from those observed in the populations of European descent. Recently, precision medicine has been used to treat inflammation by targeting key biomarkers that are involved in the process. However, there are no CRS guidelines or a consensus available from China that can be shared with the international academia. The guidelines presented in this paper cover the epidemiology, economic burden, genetics and epigenetics, mechanisms, phenotypes and endotypes, diagnosis and differential diagnosis, management, and the current status of CRS in China. These guidelines—with a focus on China—will improve the abilities of clinical and medical staff during the treatment of CRS. Additionally, they will help international agencies in improving the verification of CRS endotypes, mapping of eosinophilic shifts, the identification of suitable biomarkers for endotyping, and predicting responses to therapies. In conclusion, these guidelines will help select therapies, such as pharmacotherapy, surgical approaches and innovative biotherapeutics, which are tailored to each of the individual CRS endotypes.

Application of endoscopic nasal lateral wall dissection in lesions of the maxillary sinus / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the application of endoscopic nasal lateral wall dissection in lesions of the maxillary sinus.@*METHOD@#Ten hospitalized patients with the maxillary sinus lesions were treated with the endoscopic nasal lateral wall dissection.@*RESULT@#All 10 patients were unilateral invasion. Among them, 7 cases were inverted papilloma, 2 cases were recurrent antrochoanal polyps, 1 case was sinusal tooth. The tumors and antrochoanal polyps originated from the every part of the maxillary sinus wall during operation, especially from the anterior and media wall. During 10-62 months follow-up,epithelization of nasal occured and the shape of inferior turbinate was well. All of them had no epiphora.@*CONCLUSION@#Endoscopic nasal lateral wall dissection can remain the function of nasal lacrimal duct and nasal cavity,and may provide a new minimally invasive approach for complete resection of lesions of nasal cavity and the maxillary sinus.

Pathway analysis of the differential expression genes of oligonucleotide microarray of airway allergic diseases using GenMAPP / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To detected the mechanism of allergic rhinitis associated with asthma with bioinformatics methods.@*METHOD@#GenMAPP software was used to analyze the expression profile of nasal mucosa of seasonal allergic rhinitis(SAR) and SAR associated with asthma of oligonucleotide microarray (Affymetrix HG-U133-plus2). One the first step,of differentially expressed genes screening were done, then differential gene database retrieval was established, at last pathway analysis was performed.@*RESULT@#689 genes out of 47 000 analyzed transcripts of nasal mucosa of SAR associated with asthma were differentially expressed at least 4-fold, in which 233 genes were up regulated and 456 genes were down regulated. These differential expression genes participate in 69 bio-pathways, in which the interaction pathway between cytokine and cytokine receptor was most. Chemotactic factor CXCL12 and its receptor CXCR4 expressed in SAR associated with asthma patients were up-regulated predominantly, compared with that in SAR patients.@*CONCLUSION@#Multiple pathways were involved in the development of SAR and SAR complicated with asthma. The CXCL12/CXCR4 axis might play a main role in the allergic airway diseases.

Expression and DNA binding activity of NF-kappaB p50 in nasal mucosal tissue of seasonal allergic rhinitis / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To study the expression and activation of p50 subunit of nuclear factor-kappa B(NF-kappaB) in mucosa of seasonal allergic rhinitis.@*METHOD@#The expression of p50 subunit of NF-kappaB in the mucosa from 16 patients (6 patients with symptom, 10 patients without symptom)and 10 normal subjects were detected by immunohistochemistry. The activation of DNA-binding proteins which was labeled with 32P-radiolabeled oligonucleotide probe for NF-kappaB was detected with electrophoretic mobility shift assays(EMSA) in mucosa.@*RESULT@#The expression of p50 subunit of NF-kappaB was observed in the nasal mucosa of SAR and normal samples. The expression of p50 subunit of NF-kappaB was positive in the cytoplasm and some nuclei of the mucosal epithelia, inflammatory cells, glandular epithelia, and vascular endothelia in nasal mucosa. The Rate of nucleus positive staining of p50 was (41.83 +/- 4.43)% and(37.19 +/- 3.93)% in SAR with symptom and SAR without symptom patients,respectively. There was no significant difference (P > 0.05). The Rate of nucleus positive staining of p50 in nasal mucosa of normal samples was (8.89 +/- 1.32)%. The difference of p50 subunit of NF-kappaB expression between SAR group and normal group was statistically significant (P < 0.01). The DNA-binding proteins activity of samples from patients with seasonal allergic rhinitis was stronger than that in normal subjects (P < 0.05).@*CONCLUSION@#p50 subunit of NF-kappaB was activated in healthy nasal mucosa to some extent. The expression and DNA-binding proteins activity of p50 subunit of NF-kappaB was enhanced in seasonal allergic rhinitis. It indicated that p50 subunit of NF-kappaB may be involved in nasal mucosa physiological function and may have an important role in maintaining the chronic inflammation in seasonal allergic rhinitis.