We characterized the clinical features of PTPN11-related deafness and evaluated the outcomes of cochlear implantation in affected patients. Whole-exome sequencing and bioinformatic analyses were performed in a cohort of 467 individuals with congenital sensorineural hearing loss to identify potential genetic etiologies. Four patients harboring PTPN11 variants were reviewed for their clinical characteristics and post-implantation auditory rehabilitation outcomes. PTPN11 variants were identified in four patients (Cases 1–4). A missense variant c.1391G > C (p.Gly464Ala) in exon 12 was detected in Case 1 and the recurrent variant c.836A > G (p.Tyr279Cys) in exon 7 was identified in Case 2. Both patients were diagnosed with Noonan syndrome with multiple lentigines. Missense variants c.1510A > G (p.Met504Val) in exon 13 and c.923A > G (p.Asn308Ser) in exon 8 were found in Cases 3 and 4, respectively; both were diagnosed with Noonan syndrome. Cases 1, 2, and 4 underwent cochlear implantation and demonstrated favorable postoperative auditory and speech outcomes. Our study provides a comprehensive characterization of auditory, speech and systemic phenotypes in PTPN11-related Noonan spectrum disorders and demonstrates that cochlear implantation is highly effective for severe-to-profound hearing loss. These findings emphasize the value of early genetic diagnosis and emphasize the importance of coordinated, interdisciplinary management.

随着现代科学技术的飞速发展,临床诊疗技术和方法不断发展和完善。本专栏的开辟旨在创建一个学术交流平台,针对本学科临床工作中的热点和难点,邀请在相关领域做出大量工作并颇有建树的专家和教授,介绍他们的见解和经验,以飨读者。圆桌论坛为个人意见不具共识性。

Objectives:To explore molecular diagnoses in cochlear implantation (CI) recipients and evaluate CI outcomes in patients with PCDH15 mutations. Methods:Whole-exome sequencing and biomedical informatics were used to identify potential genetic causes in 467 individuals with congenital sensorineural hearing loss. We reviewed six CI recipients with PCDH15 mutations, assessing their CI outcomes and clinical features. Results:Nine PCDH15 variants and a heterozygous variant in CDH23 were identified in members of five families who underwent CI. Six of these were novel variants: exon 14-21 del, exon two del, exon 19 del, two splicing variants (c.2869-2A>C, c.1918-1G>A) in PCDH15, and c.209C>T in CDH23. All but one of the individuals with PCDH15 mutations exhibited autosomal recessive inheritance; one showed both digenic and autosomal recessive inheritance. Variants in PCDH15 contributed to Usher syndrome type 1F in patients 1 and 5, whereas the remaining four had isolated deafness (DFNB23). All six patients expressed satisfaction with their CI outcomes. Conclusion:CI significantly improved auditory and communication abilities in individuals with PCDH15 mutations. Early intervention is critical for achieving favorable outcomes. Preoperative genetic testing in individuals with hearing loss provides valuable insights for predicting CI success, offering potential treatments for retinal degeneration in Usher syndrome and facilitating personalized genetic counseling.

Objective:The aim of this study was to present an institution's experience with cochlear reimplantation（CRI）, to assess surgical challenges and post-operative outcomes and to increase the success rate of CRI. Methods:We retrospectively evaluated data from 76 reimplantation cases treated in a tertiary center between 2001 and 2022. Clinical features include caused of CRI, type of failure, surgical issues, and auditory speech performance were analyzed. Categorical Auditory Performance （CAP） and Speech Intelligibility Rating （SIR） scores were used to evaluate pre-and post-CRI outcomes. Our center's consecutive cohort of 1 126 patients had seven patients, while 69 patients were from other cochlear implant centers. Device failure was the most common cause of CRI（68/76）, with the remaining cases including flap complications（3/76）, magnet displacement（3/76）, secondary meningitis（1/76）, and foreign bodies around the implant（1/76）. Postoperative auditory and speech outcome improved in 31.6%（24/76） of patients, remained unchanged in 63.2%（48/76）, and decreased in CAP and SIR scores in 5.2%（4/76） of patients. Postoperatively, the seven patients with cochlear ossification and fibrosis scored lower on the overall CAP and SIR scale than non-ossification individuals, which is a significant factor in surgical success rates and auditory-speech outcomes. Conclusion:CRI surgery is a challenging but relatively safe procedure, and most reimplanted patients experience favorable postoperative outcomes. Medical complications and intracochlear damage are the main causes of poor postoperative results. Therefore, minimally invasive CI has a positive significance for reducing the difficulty of CRI surgery and improving the CI performance.

This study examined the relationships between electrophysiological measures of the electrically evoked auditory brainstem response (EABR) with speech perception measured in quiet after cochlear implantation (CI) to identify the ability of EABR to predict postoperative CI outcomes. Thirty-four patients with congenital prelingual hearing loss, implanted with the same manufacturer’s CI, were recruited. In each participant, the EABR was evoked at apical, middle, and basal electrode locations. The following EABR measures were analyzed: wave III and V input/output (I/O) function, latency, threshold, threshold0.5 μV and Gibson scoring. Patients’ speech perception abilities were assessed using the Mandarin Speech Perception (MSP) materials presented in quiet. The Categories of Auditory Performance (CAP) and Speech Intelligibility Rating (SIR) were also used to assess CI outcomes. A regression model was developed to explore the relationship between EABR and each speech measure, to identify parameters with significant predictive ability. A significantly shorter eV latency, lower eV threshold, lower eV threshold0.5 μV and steeper I/O slopes for both eV and eIII were observed when these responses were evoked at the apical electrode, compared to the middle and basal positions. Implantation age was significantly negatively correlated with bisyllables recognition rate (R2 = 0.20, p = 0.0194). The eIII slope at the apical site and the eV slope at the basal site demonstrated the highest R2 values in positive correlation with CAP, both with R2 = 0.09. Among the EABR parameters, the regression models based on MSP bisyllables recognition rate, basal eV latency, eV thresholds and threshold0.5 μV recorded at the apical and middle positions were statistically significant. Our study identified an apex-to-base gradient in EABR responsiveness following prolonged CI use. The threshold and I/O slopes of EABR appear to be informative predictors of speech perception performance in CI users, especially in the low-to-middle frequency range. However, further validation is needed.

Objectives: The aim of this study was to present an institution's experience with cochlear reimplantation (CRI), to assess surgical challenges and post-operative outcomes and to increase the success rate of CRI. Study design: Retrospective single-institution study. Setting: Tertiary medical center. Methods: We retrospectively evaluated data from 76 reimplantation cases treated in a tertiary center between 2001 and 2022. Clinical features including etiology of hearing loss, type of failure, surgical issues, and auditory speech performance were analyzed. Categorical Auditory Performance (CAP) and Speech Intelligibility Rating (SIR) scores were used to evaluate pre- and post-CRI outcomes. Results: The CRI population comprises of 7 patients from our institute,69 referred patients from other centers. Device failure was the most common reason (68/76, 89.5 %) for CRI; in addition, there were 7 medical failures and 1 had both soft device failure. Medical failures included flap rupture and device extrusion, magnet migration, auditory neuropathy, leukoencephalopathy, foreign-body residue and meningitis. In 21/76 patients, the electrode technology was upgraded. The mean time to failure was 0.58-13 years, with a mean of 4.97 years. The mean (f SD) CAP and SIR scores before and after CRI were 5.2 f 1.2 versus 5.5 f 1.1 and 3.4 f 1.1 versus 3.5 f 1.1, respectively. Performance was poor in six patients with severe cochlear malformation, auditory nerve dysplasia, leukoencephalopathy, and epilepsy. Conclusion: CRI surgery is a challenging but relatively safe procedure, and most reimplanted patients experience favorable postoperative outcomes. Medical complications and intracochlear damage are the main causes of poor postoperative results. Therefore, adequate preoperative preparation and atraumatic CRI should be carried out for optimal results.

PurposeTo evaluate the clinical validity of preimplantation genetic testing (PGT) to prevent hereditary hearing loss (HL) in Chinese population.MethodsA PGT procedure combining multiple annealing and looping-based amplification cycles (MALBAC) and single-nucleotide polymorphisms (SNPs) linkage analyses with a single low-depth next-generation sequencing run was implemented. Forty-three couples carried pathogenic variants in autosomal recessive non-syndromic HL genes, GJB2 and SLC26A4, and four couples carried pathogenic variants in rare HL genes: KCNQ4, PTPN11, PAX3, and USH2A were enrolled.ResultsFifty-four in vitro fertilization (IVF) cycles were implemented, 340 blastocysts were cultured, and 303 (89.1%) of these received a definite diagnosis of a disease-causing variant testing, linkage analysis and chromosome screening. A clinical pregnancy of 38 implanted was achieved, and 34 babies were born with normal hearing. The live birth rate was 61.1%.Conclusions and relevanceIn both the HL population and in hearing individuals at risk of giving birth to offspring with HL in China, there is a practical need for PGT. The whole genome amplification combined with NGS can simplify the PGT process, and the efficiency of PGT process can be improved by establishing a universal SNP bank of common disease-causing gene in particular regions and nationalities. This PGT procedure was demonstrated to be effective and lead to satisfactory clinical outcomes.

OBJECTIVE:To analyze binaural integration, we used a new stimulation mode of the electrically evoked auditory brainstem response (EABR), to reflect bilaterally implanted cochlear function.DESIGN:EABR was tested using the following procedure: First, both ears were evaluated separately, with the contralateral speech processor closed (C), followed by another measurement with both processors open (O). Subsequently, the eV latencies and amplitudes were assessed. The Speech, Spatial, and Qualities of Hearing Scale (SSQ), Categories of auditory performance (CAP) and speech intelligibility rating (SIR) scores were used to assess binaural hearing ability subjectively.STUDY SAMPLE:Fifteen subjects with bilateral CI from 1997 to 2018 were recruited, each diagnosed with severe to profound hearing loss.RESULTS:All SSQ scores, except for one, were greater than six (the exception scored 1.3/0.8/1.0). All CAP/SIR scores except one were greater than 6/4 (the exception scored 0/1). All patients exhibited good quality EABR measurements. The open contralateral processor significantly reduced the eV latency while enhancing the eV amplitude compared to monaural stimulation. The objective EABR results were consistent with subjective speech perception and auditory ability assessed using the SSQ scale.CONCLUSION:The EABR accurately reflected auditory pathway maturation and development after CI; thus, reflecting accordance with subjective speech and hearing performances. Furthermore, bilateral CI facilitates binaural integration and auditory brainstem plasticity.

Hearing loss (HL) is one of the most common disabilities in the world. In industrialized countries, HL occurs in 1–2/1,000 newborns, and approximately 60% of HL is caused by genetic factors. Next generation sequencing (NGS) has been widely used to identify many candidate genes and variants in patients with HL, but the data are scattered in multitudinous studies. It is a challenge for scientists, clinicians, and biologists to easily obtain and analyze HL genes and variant data from these studies. Thus, we developed a one-stop database of HL-related genes and variants, Gene4HL ( http://www.genemed.tech/gene4hl/ ), making it easy to catalog, search, browse and analyze the genetic data. Gene4HL integrates the detailed genetic and clinical data of 326 HL-related genes from 1,608 published studies, along with 62 popular genetic data sources to provide comprehensive knowledge of candidate genes and variants associated with HL. Additionally, Gene4HL supports the users to analyze their own genetic engineering network data, performs comprehensive annotation, and prioritizes candidate genes and variations using custom parameters. Thus, Gene4HL can help users explain the function of HL genes and the clinical significance of variants by correlating the genotypes and phenotypes in humans.

Background: The development of hearing and plasticity of brain after cochlear implantation (CI) for prelingually deaf children with white matter changes (group A) is unclear. Objective: To investigate the development of hearing for children in group A during 1 year after CI activation, compared with non-complicated peers (group B). Materials and methods: Twenty-one and 22 children (average age is about 5 years old) were included in groups A and B, respectively. Questionnaires were used to assess the hearing ability at pre-CI, 1, 6 and 12 months after CI activation (called Mpre, M1, M6, M12 for short). In addition, MMRs to pure tones were investigated at the same three time points after CI. Results: There is no significant difference in scores on questionnaires, MMR incidence, latency or amplitude between children in two groups. Scores on questionnaires showed a significant progressive improvement in two groups during the first year after CI. Furthermore, MMR incidence at M6 was significantly higher than that at M1, and MMR latency at M12 was significantly shorter than that at M1.

PURPOSE:To review delayed-onset skin flap complications associated with pediatric cochlear implantation (CI) in our institute, analyze the etiology, and explore effective treatment strategies.METHODS:Retrospective analyses of 811 children who had undergone cochlear implantation between January 2003 and March 2019 were performed. Twelve (1.48%) patients developed skin flap complications after CI. We present a classification of flap issues and wound histopathology following cochlear implantation. The interventions for flap problems included drug treatment, aspiration, local wound care, revision surgery, and explantation depending on the clinical situation. The temporalis myofascial reconstructive option is discussed.RESULTS:Seven subjects were cured with conservative treatment. Five cases with flap infection or necrosis underwent revision surgery, with wound closure in three cases (60%) and revision surgery with explantation in the remaining two cases (40%). Explantation ultimately led to wound healing in all cases. They all achieved excellent performance through re-implantation.CONCLUSION:Flap complications after CI are rare but treatable. Comprehensive treatments should be developed to achieve a stable and healed wound for CI.

Background Brainstem auditory evoked potentials (BAEPs) have been widely monitored to prevent hearing loss (HL) during microvascular decompression (MVD) for hemifacial spasm (HFS); however, their predictive value is still unclear. The aim of this study is to investigate the predictive values of the maximum changes in BAEPs and define the best warning indicator and a cutoff value (CV) during HFS-MVD. Methods The clinical data of 93 HFS-MVD patients were retrospectively analysed. The maximum change rates of the latency and amplitude of waves I, III, and V and the interpeak latencies (IPLs) I-III, I-V, and III-V, when BAEPs change most during MVD, were defined. Pure tone audiometry was performed to evaluate hearing loss (HL). Logistic regression, propensity score, receiver operating curve (ROC), and area under the curve (AUC) were used to identify the predictive value of relevant indexes and to determine the CV (with the largest Youden index) of the best index at different levels of HL. Results The AUCs of BAEPs for predicting HL were 0.98, 0.92, and 0.84 for 50 dB, 30 dB, and 10 dB, respectively. The amplitude of wave V (AwV) was the best single predictive index at all three HL levels. The CV of AwV was 55% (50 dB), 46% (30 dB), and 34% (10 dB). At 50 dB HL, the predictive value of IPLs I-V (AUC 0.89 with CV 0.6 ms) was better than that of LwV (AUC 0.82 with CV 1 ms). Conclusion BAEPs can predict HL well. AwV is the best single predictive index of all BAEPs. The reduction of AwV by 34% (watching), 46% (reporting), and 55% (warning) can be used as a sliding-scale warning sign. In addition, IPLs I-V (> 0.6 ms) and LwV (> 1 ms) should also be observed and reported during MVD.

目的:制备薄荷素油鼻黏膜保湿微乳,并对其黏膜黏附性和纤毛毒性进行考察.方法:以聚氧乙烯氢化蓖麻油为乳化剂制备薄荷素油鼻黏膜保湿微乳,基于综合评分以正交设计法优化微乳的制备工艺;对所制微乳进行表征并采用气相色谱法测定薄荷醇含量;通过测定蟾蜍在体纤毛传输速率评价其黏膜黏附性,测定蟾蜍离体纤毛持续运动时间以评价其纤毛毒性.结果:自制微乳的优化制备工艺为先将薄荷素油与乳化剂分散,再加入无水乙醇、食用甘油、蒸馏水混合后,于1200 r/min的转速下搅拌2 h.3批自制微乳中薄荷醇的平均含量为2.682、2.507、2.496 mg/mL,RSD为2.89％(n=3).自制微乳高、中、低剂量组(以薄荷醇计2.561、0.256、0.128 mg/mL)蟾蜍在体上颚纤毛传输速率分别为(0.65±0.01)、(0.78±0.03)、(0.92±0.04)cm/min,显著低于生理盐水组和复方薄荷脑滴鼻液组(P<0.05);蟾蜍离体上颚纤毛运动时间分别为(206.7±4.9)、(226.0±13.5)、(269.3±12.9)min,显著长于去氧胆酸钠组(P<0.05).结论:自制微乳的制备工艺可行、质量可控,其黏膜黏附性较好,无纤毛毒性.

耳聋是人类最常见的遗传疾病之一,世界不同国冢地区报告新生儿耳聋的发病翠在1～3‰.在我国大概有2780万聋人,每年有3万多先天性耳聋的新生儿出生,之前有调查显示耳聋新生儿中有54.93％是由遗传因素造成.如此庞大的耳聋及突变基因携带者家庭很大一部分具有强烈的生育正常听力下一代的意愿.目前对于阻断耳聋向子代遗传,产前诊断技术是唯一的预防手段.但由于其有创、可能面临大月份引产等带来一定的伦理争议.对于耳聋这种非致死性遗传病,胚胎植入前诊断(preimplantation genetic diagnosis,PGD)是目前国际上主流的预防手段.因此我们亟需建立一种针对中国人群耳聋遗传病特点的,简便易行、可靠性高、成功率高的胚胎植入前诊断方法.成为耳聋三级预防体系的第一道关卡.本文系统回顾了单基因遗传病尤其是遗传性耳聋胚胎植入前诊断方法的发展历史和最新进展,阐述了胚胎活检、全基因组扩增、连锁分析、染色体扫描四个胚胎植入前诊断关键技术步骤的方法及新进展.

Objective:To evaluate the clinical efficacy of Qingyan lozenges for the treatment of chronic pharyngitis.Methods:A total of 209 patients with pharyngitis who visited ENT Departments of China-Japan Friendship Hospital and The First Affiliated Hospital of Guangzhou Medical University in July 2016 were randomly divided into observation group (101 cases)and control group (108 cases),according to age,gender and severity of the disease.The observation group were treated with Qingyan lozenges and the control group with Golden Throat lozenges(OTC)for two weeks.The main complaints and local signs were collected and compared at the beginning of treatment,1 week and 2 weeks after the treatment.Results:After taking Qingyan lozenges,the effective rate was 64.4％ 1 week later,and 87.1％ after 2 weeks;while the effective rate of the Golden Throat lozenges group was 64.8％ at 1 week,and 84.3％ 2 weeks later.There was no significant difference between the 2 groups (P＞0.05).After 1 week,the comprehensive scale improvement degrees of Qingyan lozenges group were 4.4 and 6.7 points,and Golden Throat lozenges patients' were 4.5 and 6.4 points.After 1 week and 2 weeks Qingyan lozenges therapy,the self-induction scale and signs of the scale improvement degrees were 2.1,2.7 and 2.3,4.0 points;and control group improvement degrees were 2.2,2.6 and 2.3,3.8 points.The differences between the 2 groups had not statistically significant(P＞0.05).Conclusion:Qingyan lozenges has the same clinical effect as Golden Throat lozenges for chronic pharyngitis and has good application value.

OBJECTIVETo explore the application of immediate recurrent laryngeal nerve reconstruction in the treatment of thyroid cancer invading the recurrent laryngeal nerve.METHODSTen patients with thyroid cancer invading unilateral recurrent laryngeal nerve underwent radical surgery and immediate recurrent laryngeal nerve reconstruction. The reconstructive surgical approach included recurrent laryngeal nerve decompression surgery, end-to-end anastomosis of the recurrent laryngeal nerve, anastomosis of ansa cervicalis nerve to the recurrent laryngeal nerve, and nerve-muscle pedicle (NMP) technique. Among the ten patients, one underwent nerve decompression, one underwent end-to-end anastomosis of the recurrent laryngeal nerve, seven had anastomosis of ansa cervicalis to recurrent laryngeal nerve, and one case had anastomosis of ansa cervicalis to recurrent laryngeal nerve combined with nerve-muscle pedicle (NMP) technique. The effect of surgery was evaluated by videolaryngoscopy, maximum phonation time (MPT), phonation efficiency index (PEI) and voice assessment. T-test was used in the statistical analysis.RESULTSAll of the 10 patients had no complications including tumor recurrence and hypoparathyroidism after the surgery. Their hoarseness symptoms were improved, and the patients returned to normal or near-normal voice. Postoperative videolaryngoscopy showed that paralyzed vocal cord returned to normal muscle tone and volume, and the vocal cord vibration and mucosal wave were symmetric and the patients got good glottal closure. The pre- and post-operative maximum phone times of the patients were (4.52 ± 0.89) s and (11.91 ± 1.87) s, respectively (P < 0.01). The pre- and post-operative phonation efficiency indices were (1.37 ± 0.43) s/L and (4.02 ± 1.33) s/L, respectively (P < 0.05).CONCLUSIONSIn patients with thyroid cancer invading unilateral recurrent laryngeal nerve, immediate recurrent laryngeal nerve reconstruction following radical surgery of thyroid cancer can effectively achieve recovery in phonation function and improve the quality of life of the patients.

>耳聋是常见致残性疾病,是我国的重大公共卫生问题。据2012年的残疾人调查结果显示,我国因聋致残者多达2 054万人。新生儿耳聋发生率为0.1% 0 .3%,即每年新生2～3万例耳聋患儿[1],这一数字提示,我国的防聋治聋工作任务艰巨。一、与耳聋相关的基因突变全国性聋病分子流行病学调查显示,我国耳聋群体中60%为遗传性耳聋[2]。GJB2基因突变是最常见的致聋因素,我国耳聋患者中21.6%携带

Objective To study the feasibility and rehabilitation outcomes of one -stage cochlear implantation (CI) in profound deaf children with secretory otitis media (SOM ) .Methods A total of 11 profound deaf children with soal receired one -soage unilateral cochlear implantation with a follow -up period from 13~60 months .In-flamed mucosa in the mastoid as well as exudates were removed radical1y at the time of implantation for adequate drainage of the middle ear .After the sugery ,the patients were followed up and the hearing and rehabilitating out-comes were eveluated .Results All 11 patients were successfully operated with 8 cases in the right ear and 3 cases in the left ear .Among them ,7 cases were nucleus 24 CA ,1 case losa clarion AB 90 K ,2 cases were medel combi 40+and 1 case was pulsar .All patients were successfully operated .No infectious complications occurred .No recurrence of secretory otitis media was observed .After initial stimulation and post regular fitting ,the status of the implant-able devices were all stable .All the implantees had satisfied hearing and entered normal kindergartens or schools . Conclusion Profound deaf pediatric patients with SOM are not an absolute contraindication for CI .With sufticient pre-operation preparontion ,proper trentment and nursing .Cochlear implantation should be condnote as early as possible better rehabilitation performance .

<正>1概述咽旁间隙位于颅咽筋膜的外侧,呈一倒置的三棱形,上至颅底,下达舌骨平面,以茎突及茎突诸肌为界分为咽旁前、后间隙。咽旁前间隙较小,内有腭帆提肌、腭帆张肌、