先天性耳廓畸形是颌面部的常见畸形,影响患儿面容及心理发育.非手术矫正纠正先天性耳廓畸形疗效确切,避免了手术治疗带来的风险.本文旨在对先天性耳廓畸形的发病机制、分类等方面进行综述,并对耳模矫正技术的类型、治疗时机、影响疗效的因素及并发症进行归纳,以期促进耳廓畸形非手术矫正技术在临床上的应用.

2019新型冠状病毒（2019 novel coronavirus，2019-nCoV）感染已被纳入《中华人民共和国传染病防护法》规定的乙类传染病，并采取甲类传染病预防控制措施。耳鼻咽喉头颈外科急症食管异物、呼吸道异物、鼻出血、喉阻塞合并呼吸困难及头颈部外伤发病率相对较高，部分可迅速危及生命的急症需紧急手术。本文根据新型冠状病毒肺炎诊疗方案（试行第五版），在疫情蔓延地区结合华中科技大学同济医学院附属协和医院耳鼻咽喉科急诊手术处理的经验，现总结制订了新型冠状病毒防控期间耳鼻咽喉头颈外科急症手术诊疗建议，以期在新型冠状病毒防控期间提高耳鼻咽喉头颈外科急症的救治成功率及减少或避免围手术期医护人员新型冠状病毒感染可能。

The 2019 Novel Coronavirus (2019-nCoV, SARS-CoV-2) infection has already been assigned as a Class B infectious disease requiring Class A management strategy according to "the Law on the Prevention and Control of Infectious Diseases of the People's Republic of China" and become a global pandemic. The incidence of emergencies in otorhinolaryngology, head and neck surgery such as foreign bodies in the esophagus and the respiratory tract, epistaxis, laryngeal obstruction with dyspnea, and head and neck trauma are relatively high. Emergency surgeries are required as some of these diseases progress rapidly and probably be life-threatening. In this article, we drafted the recommendations for diagnosis and treatment of emergency surgeries in otorhinolaryngology, head and neck surgery in the epidemic area of novel coronavirus pneumonia based on "Novel Coronavirus Pneumonia Diagnosis and Treatment Plan (Provisional; 7th Edition Revisions)"and WHO guidelines, combined with the experience of emergency surgeries in the Department of Otorhinolaryngology, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, which is at the center outbreak area of the SARS-CoV-2 pneumonia (COVID-19) in China, to improve the success rate of treatment for otorhinolaryngology, head and neck surgery emergency surgeries and to reduce the SARS-CoV-2 infection rate in the perioperative period.

Age‐associated degeneration in the central auditory system, which is defined as central presbycusis, can impair sound localization and speech perception. Research has shown that oxidative stress plays a central role in the pathological process of central presbycusis. Thioredoxin 2 (Trx2), one member of thioredoxin family, plays a key role in regulating the homeostasis of cellular reactive oxygen species and anti‐apoptosis. The purpose of this study was to explore the association between Trx2 and the phenotype of central presbycusis using a mimetic aging animal model induced by long‐term exposure to d‐galactose (d‐Gal). We also explored changes in thioredoxin‐interacting protein (TXNIP), apoptosis signal regulating kinase 1 (ASK1) and phosphorylated ASK1 (p‐ASK1) expression, as well as the Trx2–TXNIP/Trx2–ASK1 binding complex in the auditory cortex of mimetic aging rats. Our results demonstrate that, compared with control groups, the levels of Trx2 and Trx2–ASK1 binding complex were significantly reduced, whereas TXNIP, ASK1 p‐ASK1 expression, and Trx2–TXNIP binding complex were significantly increased in the auditory cortex of the mimetic aging groups. Our results indicated that changes in Trx2 and the TXNIP–Trx2–ASK1 signal pathway may participate in the pathogenesis of central presbycusis.

OBJECTIVE:To investigate characteristics of molecular etiology of children with profound sensorineural hearing loss in Hubei province, and to provide reference for deafness treatment and genetic counseling.METHOD:Three hundred and six children with profound sensorineural hearing loss in Hubei province were enrolled, their genomic DNA were extracted from peripheral blood and a deafness gene test chip was used to screen nine hot spot mutation in the GJB2, GJB3, SLC26A4, and mitochondria 12SrRNA gene. All patients with SLC26A4 gene mutation were given temporal bone CT scan.RESULT:One hundred and thirty-two (43.14%) out of 306 children were found carrying at least one pathogenic gene mutation. The mutation rates of GJB2, SLC26A4 and mitochondria DNA 12SrRNA gene were 29.41% (90/306), 13.72% (42/306) and 0.65% (2/306), respectively. None out of 306 children was detected GJB3 gene mutation. Thirty-six patients carrying SLC26A4 gene mutation were detected enlarged vestibular aqueduct by CT scan.CONCLUSION:Mutations of GJB2 and SLC26A4 gene are two major pathogenic gene for genetic hearing loss in children. 235delC mutation is the main mutation type, followed by IVS7-2A> G mutation type. The screening of SLC26A4 gene common mutations contribute to the diagnosis of enlarged vestibular aqueduct syndrome.

Presbycusis is the most common functional disabling disease, the pathogenesis of which has not been clarified up to now and there is lack of effective treatment method for this reason. It has been recently reported that it is a com-prehensive disease resulted from the interaction between the hereditary factors and environmental factors. The 4977bp deletion of presbycusis in human (The 4834bp deletion of mitochondrial DNA in rat) were called the Common Dele-tion, which were considered relating to the Presbycusis. The aim of this paper is to review the studying of the presbycusis associated with mitochondrial DNA deletion, present the progress in pathogenesis and therapy research( using the es-tablished in vivo and in vitro model) of this presbycusis .

In humans, chronic dyslipidemia associated with elevated triglycerides may reduce auditory function. However, there is little evidence available in the literature concerning the effects of a long-term high-fat diet (HFD) on the inner ears of animals. The purpose of this study was to investigate the effect of 12 month-HFD on the inner ear of Sprague–Dawley rats and on the d-galactose (d-gal)-induced aging process in the inner ear. We found that 12 month-HFD markedly elevated the auditory brainstem response (ABR) threshold in the high-frequency region. The HFD significantly increased the generation of reactive oxygen species (ROS) and the expressions of NADPH oxidase (NOX) and the uncoupling proteins (UCP). Furthermore, an elevated accumulation of the mitochondrial DNA (mtDNA) common deletion (CD) and mitochondrial ultrastructural changes in the inner ear suggested that there was mitochondrial damage in response to the excessive fat intake. The expression level of cleaved caspase-3 and the number of terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end-labelling (TUNEL)-positive cells in the inner ear were increased by the HFD. The effects of d-gal on the inner ears were similar with 12 month-HFD. We found that rats receiving both the HFD and d-gal exhibited a greater shift in the ABR threshold, larger increases in the expression levels of NOX, UCP and cleaved caspase-3 and an increased number of TUNEL-positive cells in the inner ear. The present study demonstrated that HFD may induce oxidative stress, mitochondrial damage and apoptosis in the inner ear, and it provided evidence regarding the link between HFD and an increased risk of age-related hearing loss.

OBJECTIVE:To investigate the influence of overexpression of manganese superoxide dismutase (MnSOD) of stria marginal cells (MCs) of the rat cochlea by the recombinant adeno-associated viruses of the serotypes 2 (AAV2) mediated gene-delivery for hydrogen peroxide-induced oxidative stress in vitro.METHOD:Primary cultures of MCs were infected using rAAV2-MnSOD-EGFP at dosage of multiplicity of infection (MOI) 10(1)v x /cell and using rAAV2-EGFP as control. The expression of MnSOD in MCs was examined using western blot and the activity of MnSOD was determinated by colorimetric assays. Oxidative stress was induced in MCs by exposing them to H2O2 (400 micromol/L) for 2 hour and preculturing them in normal medium. After 24 h the amount of the lipid peroxidation production malondialdehyde (MDA) was detected. Apoptosis was assessed by flow cytometry by Propidium oidium staining. The expression of the cleaved Caspase-3 was assessed by Western blot.RESULT:(1) EGFP expression in MCs could not be detected until 4 days after rAAV2- MnSOD-EGFP infection and reached fastigium after 10 days and lasted over a month. The MnSOD level in the rAAV2- MnSOD-EGFP group was higher than that in the control group. (2) After being exposed to H2O2, the amounts of MDA in rAAV2-MnSOD-EGFP group, control group and normal group were 0.464 +/- 0.049, 1.103 +/- 0.033 and 0.185 +/- 0.005 (nmol/mg prot), respectively. The expression of the cleaved-caspase-3 in rAAV2-MnSOD-EGFP group was lower than that in control group and the number of apoptotic cells decreased significantly.CONCLUSION:The results demonstrate that the rAAV2-MnSOD-EGFP can effectively transfect cultured MCs, and the transgenic cells show a high expression of MnSOD which can protect the MCs against oxidative challenge. The role of overexpression MnSOD in MCs apoptosis induced by oxidative injury may be associated with suppressing the activation of caspase-3.

Oxidative damage to mtDNA is associated with excessive reactive oxygen species production. The mitochondrial common deletion (mtDNA 4977-bp and 4834-bp deletion in humans and rats, respectively) is the most typical and frequent form of mtDNA damage associated with aging and degenerative diseases. The accumulation of the mitochondrial common deletion has been proposed to play a crucial role in age-related hearing loss (presbycusis). However, the mechanisms underlying the formation and accumulation of mtDNA deletions are still obscure. In the present study, a rat mimetic aging model induced by D-Gal was used to explore the origin of deletion mutations and how mtDNA repair systems modulate this process in the inner ear during aging. We found that the mitochondrial common deletion was greatly increased and mitochondrial base excision repair capacity was significantly reduced in the inner ear in D-Gal-treated rats as compared with controls. The overexpression of mitochondrial transcription factor A induced by D-Gal significantly stimulated mtDNA replication, resulting in an increase in mtDNA copy number. In addition, an age-related loss of auditory sensory cells in the inner ear was observed in D-Gal-treated rats. Taken together, our data suggest that mitochondrial base excision repair capacity deficiency and an increase in mtDNA replication resulting from mitochondrial transcription factor A overexpression may contribute to the accumulation of mtDNA deletions in the inner ear during aging. This study also provides new insights into the development of presbycusis.

OBJECTIVE:Use the inner ear mimetic aging model which has been established by our research institute, investigate its sensitivity to noise trauma and the possible role of mitochondrial DNA deletions.METHOD:Thirty-two Wistar rats of 2 months old were randomly divided into four groups. In group A, D-galactose was subcutaneously injected at dose of 150 mg/kg weigh per day for 8 weeks, after that these rats were exposed to 110 dB SPL noise 4 hours each day, for 2 days. Group B were given normal saline (NS) injected at dose of 150 mg/kg weigh per day for 8 weeks,also given noise exposure as that of group A. Group C were give D-galactose without noise exposure. Group D were given normal saline (NS) without noise exposure. The thresholds of auditory brainstem response (ABR) were measured 2 weeks after stopping of noise exposure. And T-SOD and MDA of the inner membranous labyrinthine tissue were measured. Nest polymerase chain reaction (Nest PCR) were used to identify the mtDNA common deletion (CD), and PCR products were sequenced in the meantime.RESULT:The elevation of the mean ABR thresholds in group A was higher than that in group B, and the difference had statistic significance (P < 0.01). The reduction of T-SOD in group A was obvious, while the level of MDA was greatly increased. The difference in the levels of T-SOD and MDA between group A and group B had statistic significance (P < 0.01). The detection rate of mtDNA 4834 deletion were as follows: group A 87.5% (7/8); group B 12.5% (1/8); group C 75.0% (1/8); group D 0(0/8).CONCLUSION:The rat in the inner ear mimetic aging model are hypersensitive to noise exposure, and mtDNA4834 deletions in the inner ear may play an important role in it.

OBJECTIVE:To observe the expression of mGluR5 in the medial vestibular nucleus (MVN) following unilateral labyrinthectomy (UL).METHOD:Thirty Wistar rats were randomly divided into two groups. Twenty four animals received unilateral labyrinthectomy while the others maintained labyrinthine well. After setting left labyrinthine, the change of mGluR5 was induced by immunohistochemistry, in situ hybridization.RESULT:mGluR5 was increased in lesioned side MVN after unilateral labyrinthectomy. The 12 h post-UL was highest. Then it was decrease in 36 h post-UL, while 7 d post-UL was same as control group. The change of contralateral was same as that in ipsilateral.CONCLUSION:UL can induce increase of mGluR5 in the MVN. The reduced resting discharge in the primary vestibular afferents or in the central vestibular neurons may be responsible for the change of mGluR5. However the significance of the change of mGluR1 in the vestibular compensation is still unknown.

Objective Plasmids, recombinant adenoviruses(rAds), and adeno-associated viruses(rAAVs) are frequently used vectors, each with distinctive characteristics that may be advantageous in cochlea gene therapy. Although the general advantages and disadvantages of these vectors had been evaluated, there were no data available on the delivery of extrogene to marginal cells(MCs) of the stria vascularis(SV) in primary culture using nonviral and viral vectors. Methods In this study, the rat cochlear SV MCs were transfected with plasmid vector-pEGFPN1, rAd5, and rAAV2. The transfection efficiency, the incidence of cellular apoptosis and cell's activity were evaluated after transfection. Results The transfection rates were as follows: pEGFP-N1, 23.65-45%; rAAV2, 46.89-88%; and rAd5, 78.89-99%. The MCs viabilities after transfection were as follows: PEGFP-N1, 75.79-85.93% (average 80.7%); rAAV2, 97.54-99.76%(average 98.32%); rAd5, 88.62-93.3%(average 91.00%); and normal control, 98.93-99.89%(average 99.27%). The proportions of early apoptotic cells, end- stage apoptotic and dead cells were as follows: pEGFPN-1-transfected MCs, 39.8%; rAAV2-transfected MCs, 2.4%; and rAd5-transfected MCs, 9.2%. Conclusion Our results indicated that viral vectors were more reliable and efficient vehicles for gene transfer to the SV MCs of cochlea compared to plasmid vector. Given its high transfection efficiency and low cytotoxicity, rAd5 was more suitable for transfection of SV MCs in vitro.

OBJECTIVE To set up the oxidative stress experimental model of rat cochlea with stria vascularis marginal cells injury induced by hydrogen peroxide in vitro. METHODS Cultured marginal cells of rat were treated by 200, 300, 400, 600 and 800 micromol/L hydrogen peroxide (H(2)O(2)) for 0.5, 1, 2, 4, 16 and 24 hours, respectively. Cell viability was assessed by the CCK-8 assay. The content of the lipid peroxidation production malondialdehyde (MDA) were detected in H(2)O(2) induced marginal cells injury with different concentration H(2)O(2). Apoptosis was assessed by flow cytometry by propidium sodium staining. The expression of the cleaved-caspase-3 was assessed by Western blot. RESULTS Being exposed to H(2)O(2), marginal cells displayed nuclear pyknosis and margination, cytoplasmic condensation, cell shrinkage and formation of membrane and bounded apoptotic bodies. A time-dependent and dose-dependent decrease of cellular viability was detected with the treatment of H(2)O(2). Cellular maleic dialdehyde was generated in proportion to the concentration of H(2)O(2) at 2 hours and the number of apoptotic cells increased significantly (P < 0. 05). Western blot showed the expression of the cleaved-caspase-3 increased when 200 micromol/L, 300 micromol/L and 400 micromol/L H(2)O(2) treated cultured marginal cells. Thereafter the expression of the cleaved-caspase-3 decreased with 600 micromol/L H(2)O(2) and with 800 micromol/L H(2)O(2) the expression of cleaved-caspase-3 was weak. CONCLUSIONS The findings indicated that the experimental model can be established successfully using cultured cells exposed to H(2)O(2) and activation of caspase-3 is associated with hydrogen peroxide induced rat marginal cells the oxidative stress injury.

OBJECTIVE:To research the animal model with mimetic aging effect in the inner ear predispose to the ototoxicity of kanamycin.METHODS:Fifty wistar rats were randomly divided into four groups: group A (D-galactose group, n = 14) were treated with hypodermic 5% D-galactose (150 mg x kg(-1) x d(-1)) for 8 weeks and then with intraperitoneal saline for 10 days; group B (D-galactose and kanamycin group, n = 14) were given the same dose of D-galactose but kanamycin (500 mg x kg(-1) x d(-1)) instead of saline; group C (kanamycin group, n = 12) were treated with saline for 8 weeks and then with intraperitoneal kanamycin for 10 days;group D (control group, n = 10) were given saline only. Auditory brainstem response (ABR) was used to detect the hearing threshold of rats and colorimetry was used to analyze the activity of the GSH-PX. The inner ear tissue was harvested and the mitochondrial DNA was amplified to identify the 4834 bp deletion mutation by nested primer polymerase chain reaction (nested PCR) technique.RESULTS:The incidence of mitochondrial DNA 4834 bp deletion mutation was 100% (28/28) in group A, 92.86% (26/28) in group B and 0% in group C or group D. The activity of GSHPX in group A was (59.07 +/- 8.70)U, (63.29 +/- 12. 40)U in group B, (136.67 +/- 9.53)U in group C and (142.10 +/- 7.02)U in group D. The difference between group A and D was significant (P = 0.000) while the difference between group A and B was not significant (P = 0.307), which was similarly as between group C and group D (P = 0.151). ABR threshold was (5.36 +/- 3.08) dB peSPL in group A, (61.79 +/- 11.20) dB peSPL in group B, (34.17 +/- 4.69) dB peSPL in group C and (6.50 +/- 3.37) dB peSPL in group D. No difference was found between group A and D (P = 0.398) while the difference in shift of ABR threshold between group B and group C (or group D) was significant (P = 0.000).CONCLUSIONS:The mimetic aging effect in the inner ear of the rat can be induced by D-galactose, and these rats present high incidence of mtDNA4834 deletion which can greatly enhance the sensitivity of the inner ear to the kanamycin.

Objective Eukaryotic expression plasmid of rat Mn-superoxide dismutase(MnSOD) gene rAAV2-IRES-EGFP/MnSOD was constructed and its expression was examined in primary cultured marginal cells(MCs) from the stria vascularis(SV) and cochlear tissue of the rats.Methods The targeted segments were obtained from rat myocardial tissue and were inserted into an eukaryotic expression plasmid pEGFP-N1/MnSOD or rAAV2-IRES-EGFP/MnSOD.Then the recombinant adeno-associated viral vector 2-IRES-EGFP/MnSOD(rAAV2-IRES-EGFP/MnSOD) particles were obtained.The expression of gene of interest was detected by confocal fluorescence microscopy,fluorescence activated call sorting(FACS),RT-PCR and Western blotting.Results Rat MnSOD cDNA eukaryotic expression plasmid pEGFP-N1/MnSOD and rAAV2-IRES-EGFP/MnSOD were successfully constructed.MnSOD protein could be detected in the MCs and cochlear tissue after transfection.Conclusion Rat MnSOD cDNA eukaryotic expression plasmid rAAV2-IRES-EGFP/MnSOD was successfully constructed and expressed in MCs and cochlear tissue of the rat.This results provide a basis for the antioxidant gene therapy for inner ear diseases.

近年来,随着耳外科技术的发展及生物医学工程领域的进步,围绕着感音神经性耳聋、耳发育畸形、复杂中耳病变等的替代治疗,取得了很大的进步,植入式助听装置为重要代表之一.

OBJECTIVE:To investigate the balance function of the patients with unilateral vestibular hypofunction (UVH) by timed balance tests and static posturography (SPG). METHODS:Sixty-five subjects with UVH and 92 healthy subjects were taken the timed balance tests under differential stance including (1) standard Romberg test, (2) feet apart stance test, (3) tandem and (4) unilateral standing tests with eyes open and eyes closed. The average timing that subjects kept balance before falling in each standing conditions was recorded by stopwatch as the timed result. The body sway velocity during the test (1) and (2) were also recorded by the SPG. RESULTS:The timed results of the tandem and unilateral standing with eyes open and eyes closed in the UVH group were decreased (P < 0.001) compared with the control group. The body sway velocity of the standard Romberg test and foot apart stance with eyes open was not different between the UVH group and control group (P-value was 0.118 and 0.110 for the two tests respectively), and the difference was significant in the eyes closed condition (P < 0.001). For the two groups, the body sway velocity of foot apart standing was decreased than that of the standard Romberg test with eyes open and eyes closed (P < 0.05 or P < 0.001). Significant correlations were not found between the timed results and sway velocity results in both two groups respectively (P > 0.05). CONCLUSIONS:According to clinical assessment of balance function in UVH, the tandem and unilateral stance test could provide the additional information about the upright stance to the SPG measurement. The effect of foot position on the results of SPG should been considered in clinic.

Objective To investigate the effect of head extension on the postural stability in the healthy young subjects. Methods Thirty-four healthy young subjects were tested using posturography under four conditions, including (1) firm surface and head erected; (2) firm surface and head extension; (3) foam surface and head erected; (4) foam surface and head extension. Each condition was tested under eye open (EO) and closed (EC). The body sway velocity (SV) was analyzed. Results (1) SV under foam surface was greater than those under firm surface with EO(t = 15.484, P 0.001) and EC(t = 19.302, P 0.001) when the head was in the erect position. (2) The difference of SV between the head erect and the head extension was not significant regardless of whether the surface was firm or foamy when the eye was open. While under eye closed, the SV with head extension was greater than that with head erect under the two surface conditions. (3) The body sway increase ratio obtained on a foam surface was greater than that on a firm surface when the head was extended with eye closed (t = 5.757, P 0.001). Conclusion The human standing balance is impaired when the proprioceptive input is interrupted. The postural stability is reduced when the head of normal individuals is put in a extended position during standing with eye closed. Head extension may make the body more reliance on the proprioceptive input.