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MEFV,IRF8,ADA,PEPD,and NBAS gene variants and elevated serum cytokines in a patient with unilateral sporadic Meniere's disease and vascular congestion over the endolymphatic sac

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Journal of Otology 2022年第3期17卷 175-181页

作者： Jing Zou Zikai Zhao Guoping Zhang Qing Zhang Ilmari Pyykko Department of Otolaryngology-Head and Neck Surgery Changhai HospitalSecond Military Medical UniversityShanghaiChina Faculty of Information Technology and Communication Sciences Tampere UniversityTampereFinland Hearing and Balance Research Unit Field of OtolaryngologySchool of MedicineFaculty of Medicine and Health TechnologyTampere UniversityTampereFinland

The etiology and underlying mechanism of Meniere's disease(MD)development are still unknown,although inflammation and autoimmunity have been implicated as underlying mechanisms.The human endolymphatic sac(ES)has been reported to have innate and adaptive immune capacity in local immune reactions.In vivo demonstration of inflammation of the ES in patients with MD is missing in the literature.We report the case of a 47-year-old female patient diagnosed with unilateral MD with genetic variants and cytokine markers indicating inflammation and vascular congestion of the ES.Endolymphatic hydrops in the right cochlea(grade 2)and vestibulum(grade 3)were detected using MRI.She carried heterozygous variants in MEFV(c.442G>C),IRF8(c.1157G>T),ADA(c.445C>T),PEPD(c.151G>A),NBAS(c.4049T>C),CSF2RB(c.2222C>T),HPS6(c.277G>T),IL2RB(c.1109C>T),IL12RB1(c.1384G>T),IL17RC(c.260_271del GCAAGAGC TGGG),LIG1(c.746G>A),RAG1(c.650C>A),and SLX4(c.1258G>C,c.5072A>G).In the serum,the levels of granulocyte colony-stimulating factor(G-CSF),macrophage inflammatory protein 1a,and IL7 were significantly elevated,and the level of IL2Ra was reduced.Intratympanic administration of dexamethasone temporarily alleviated her hearing loss.Her vertigo was significantly relieved but remained slight after ES administration of corticosteroids.

关键词： Meniere's disease Autoinflammation Autoimmune Immune organ Endolymphatic sac

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Postaurical injection is a systemic delivery supported by symmetric distribution of Gd-DOTA in both the ipsilateral and contralateral ears

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Journal of Otology 2015年第4期10卷 136-142页

作者： Jing Zou Department of Otolaryngology-Head and Neck Surgery Center for Otolaryngology-Head&Neck Surgery of Chinese PLA Changhai Hospital Second Military Medical University Hearing and Balance Research Unit Field of Oto-laryngology School of Medicine University of Tampere

Postaurical injection of therapeutics was recently applied in clinical practice to treat inner ear diseases based on supposed existence of a direct channel from the postaurical area to the inner ear. Doubting on the associated reports and aiming to provide evidence on the inner ear uptake mechanism, the present study tracked the dynamic distribution of gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid (Gd-DOTA) in rat inner ears after postaurical injection using MRI. A targeted tympanic medial wall delivery was utilized as control. The results showed that, at the early time points after postaurical injection, Gd-DOTA distributed mainly in tissues surrounding the bulla, temporal bone and skull and neck space. In the inner ear, there was gradual uptake of Gd-DOTA on both the ipsilateral and contralateral sides with equal signal intensities. There was no sign of direct channel carrying the agent from the postaurical area to the inner ear. Targeted tympanic medial wall delivery induced significantly greater uptake of Gd-DOTA in the inner ear than did postaurical injection. At 30 min post-administration, targeted tympanic medial wall delivery yielded 4.6-folds higher signal intensity than did postaurical injection. The total dose of Gd-DOTA delivered by the targeted tympanic medial wall approach was only 0.1% of that delivered by postaurical injection. In conclusion, postaurical injection is a systemic administration, which is similar to hypodermic injection, rather than a focal delivery method. By contraries, targeted tympanic medial wall delivery induces fast and abundant uptake of Gd-DOTA in the ipsilateral inner ear without significant distribution in unwanted areas.

关键词： Focal drug delivery Inner ear Intratympanic delivery Hypodermic injection Magnetic resonance imaging

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Dexamethasone does not affect endolymphatic hydrops(EH)in patients with Meniere's disease within 24 h,and intratympanic administration of gadolinium plus dexamethasone simplifies high-quality imaging of EH using a novel protocol of 7 min

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Journal of Otology 2022年第3期17卷 164-174页

作者： Jing Zou Zikai Zhao Hongbin Li Guoping Zhang Qing Zhang Jianping Lu Ilmari Pyykko Department of Otolaryngology-Head and Neck Surgery Changhai HospitalSecond Military Medical UniversityShanghaiChina Department of Radiology Changhai HospitalSecond Military Medical UniversityShanghaiChina Faculty of Information Technology and Communication Sciences Tampere UniversityTampereFinland Hearing and Balance Research Unit Field of OtolaryngologySchool of MedicineFaculty of Medicine and Health TechnologyTampere UniversityTampereFinland

Background:Intratympanic administration of gadolinium chelate allows for a better visualization of endolymphatic hydrops(EH)using MRI than intravenous injection and was recently further improved to facilitate high-quality imaging of EH in 7 min.The aim of the present study was to simplify the intratympanic administration protocol by mixing gadolinium chelate with therapeutic dexamethasone and to evaluate the effects of this mixture on the visualization of EH in MRI.Materials and methods:In an in vitro study,the potential impact of gadolinium-diethylenetriamine pentaacetic acid(Gd-DTPA)on the stability of dexamethasone was evaluated by analyzing dynamic changes in dexamethasone with high-performance liquid chromatography(HPLC)after mixing with GdDTPA.Ten patients with definite Meniere's disease(MD)were recruited to study the potential interference of dexamethasone on MRI visualization of EH,and 49 patients with MD were recruited to evaluate the effect of intratympanic injection of Gd-DTPA mixed with dexamethasone on MRI of EH using a 3T MR machine and a novel heavily T2-weighted 3-dimensional fluid-attenuated inversion recovery reconstructed using a magnitude plus zero-filled interpolation(hT2FLAIR-MZFI)sequence.Results:The retention times and peak area of dexamethasone in HPLC were not modified by the addition of Gd-DTPA.EH grading in the cochlea and vestibule was not influenced in any ear by intratympanic injection of dexamethasone.Excellent inner ear images were obtained from all patients,and EHs with various grades were displayed.There were significant correlations between diagnosis and cochlear EH(p<0.01,Spearman's Rho),between diagnosis and vestibular EH(p<0.01,Spearman's Rho),and between cochlear and vestibular EH(p<0.01,Spearman's Rho).The distribution of Gd-DTPA plus dexamethasone negatively correlated with the grade of vestibular EH.Injury of the endolymph-perilymph barrier was detected in one cochlea and three vestibules of 59 inner ears with MD.Conclusions:Intratympanic administration of Gd-DTPA plus d

关键词： Meniere's disease Endolymphatic hydrops MRI Contrast agent Therapeutics Topical administration

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Label-free visualization of cholesteatoma in the mastoid and tympanic membrane using CARS microscopy

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Journal of Otology 2016年第3期11卷 127-133页

作者： Jing Zou Antti Isomaki Timo Hirvonen Antti Aarnisalo Jussi Jero Ilmari Pyykko Department of Otolaryngology-Head and Neck Surgery Center for Otolaryngology-Head&Neck Surgery of Chinese PLAChanghai HospitalSecond Military Medical University Hearing and Balance Research Unit Field of Oto-laryngologySchool of MedicineUniversity of Tampere Biomedicum Imaging unit Faculty of MedicineUniversity of Helsinki Department of Otorhinolaryngology-Head and Neck Surgery Helsinki University Central Hospital

Objective:The present study aimed to evaluate the possibility of using coherent anti-Stokes Raman spectroscopy（CARS） microscopy to determine the specific molecular morphology of cholesteatoma by detecting the natural vibrational contrast of the chemical bonds without any staining.Materials and methods:Specimens from the mastoid and tympanic membrane with and without cholesteatoma were analyzed using CARS microscopy,two-photon excited fluorescence（TPEF） microscopy,and the second harmonic generation（SHG） microscopy.Results:In cholesteatoma tissues from the mastoid,a strong resonant signal at 2845 cm;was observed by CARS,which indicated the detection of the CH;hydro-carbon lipid bonds that do not generate visible signals at 2940 cm;suggestive of CH;bonds in amino acids.A strong resonant signal at 2940 cm;appeared in an area of the same specimen,which also generated abundant signals by TPEF and SHG microscopy at 817 nm,which was suggestive of collagen.In the tympanic membrane specimen with cholesteatoma,a strong resonant signal with corrugated morphology was detected,which indicated the presence of lipids.A strong signal was detected in the tympanic membrane with chronic otitis media using TPEF/SHG at 817 nm,which indicated collagen enrichment.The CARS and TPEF/SHG images were in accordance with the histology results.Conclusion:These results suggest the need to develop a novel CARS microendoscope that can be used in combination with TPEF/SHG to distinguish cholesteatoma from inflammatory tissues.

关键词： Cholesteatoma Imaging Label-free Raman spectroscopy High resolution

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Inner ear barriers to nanomedicine-augmented drug delivery and imaging

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Journal of Otology 2016年第4期11卷 -页

作者： Jing Zou Ilmari Pyykk Jari Hyttinen Department of Otolaryngology e Head and Neck Surgery Center for Otolaryngology e Head & Neck Surgery of Chinese PLAChanghai HospitalSecond Military Medical University Hearing and Balance Research Unit Field of OtolaryngologySchool of MedicineUniversity of Tampere Department of Electronics and Communications Engineering Bio Medi TechTampere University of Technology

There are several challenges to inner ear drug delivery and imaging due to the existence of tight biological barriers to the target structure and the dense bone surrounding it. Advances in imaging and nanomedicine may provide knowledge for overcoming the existing limitations to both the diagnosis and treatment of inner ear diseases. Novel techniques have improved the efficacy of drug delivery and targeting to the inner ear, as well as the quality and accuracy of imaging this structure. In this review, we will describe the pathways and biological barriers of the inner ear regarding drug delivery, the beneficial applications and limitations of the imaging techniques available for inner ear research, the behavior of engineered nanomaterials in inner ear applications, and future perspectives for nanomedicine-based inner ear imaging.

关键词： Inner ear Nanotechnology Imaging Gene delivery Contrast agents

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Endolymphatic hydrops in Meniere's disease secondary to otitis media and visualized by gadolinium-enhanced magnetic resonance imaging

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World Journal of Otorhinolaryngology 2013年第1期3卷 22-25页

作者： Jing Zou Ilmari Pyykk? Hearing and Balance Research Unit Field of Oto-laryngology School of Medicine University of Tampere

Aimed to test the hypothesis that endolymphatic hydrops in Meniere's disease(MD) may be secondary to otitis media, history of a patient who developed MD as a complication of otitis media was reviewed. The inner ear was imaged using a 3.0 Tesla MR system post-intravenous injection of gadolinium-tetraazacyclododecane-tetraacetic acid(Gd-DOTA) in a standard single dosage(0.1 mmol/kg). Both t2-spc-rst-tra-iso(T2-weighted) and heavily T2-weighted 3-dimensional fluid-attenuated inversion recovery magnetic resonance imaging [h T(2)W-3D-FLAIR] sequences were applied. As a result, in the T2-weighted images, the perilymph and endolymph, cerebrospinal fluid surrounding the eighth nerve(N8), and middle ear granulation tissue showed intense signals. In the h T(2)W-3D-FLAIR images, evident enhancement by Gd-DOTA was observed in the middle ear cavity and the perilymphatic compartments of the cochlea. Cochlear endolymphatic hydrops was implicated by the enlarged scala media in the basalturn. In general, the Gd-DOTA uptake in the vestibule was weak, and signs of vestibular endolymphatic hydrops were obvious. The N8 on the diseased side was also significantly enhanced. To conclude, endolymphatic hydrops in MD may be induced by otitis media. Cochlear endolymphatic hydrops in MD secondary to otitis media may not follow the classical pattern.

关键词： Endolymphatic hydrops Otitis media Meniere'sdisease Magnetic resonance imaging Sensorineuralhearing loss

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圆窗和卵圆窗加固术治疗外伤性上半规管骨折

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听力学及言语疾病杂志 2015年第4期23卷 351-354页

作者：邹静郑宏良高颖娜彭日顺子郑贵亮第二军医大学长海医院耳鼻咽喉头颈外科全军耳鼻咽喉头颈外科中心上海200433 Hearing and Balance Research Unit Field of OtolaryngologySchool of MedicineUniversity of TampereTampereFinland

目的探讨圆窗和卵圆窗加固术治疗外伤性上半规管骨折引发的前庭功能障碍的手术方法及效果。方法回顾性分析1例采用圆窗和卵圆窗加固术治疗的外伤性上半规管骨折患者的临床资料,讨论其诊断要点、治疗方法及疗效。结果患者头部外伤后出现... 详细信息

目的探讨圆窗和卵圆窗加固术治疗外伤性上半规管骨折引发的前庭功能障碍的手术方法及效果。方法回顾性分析1例采用圆窗和卵圆窗加固术治疗的外伤性上半规管骨折患者的临床资料,讨论其诊断要点、治疗方法及疗效。结果患者头部外伤后出现低频声诱发眩晕、耳闷、自声增强、不能忍受低频振动等前庭功能障碍症状及听力减退;颞骨高分辨率CT示左侧上半规管顶壁多发性骨折,右侧上半规管壁单发骨折;诊断为上半规管骨折。在局麻下,耳内切口探查鼓室,用腹壁脂肪填塞圆窗,颞肌筋膜覆盖圆窗脂肪及镫骨底板周围,纤维蛋白组织胶密封颞肌筋膜与鼓室粘膜连接处;用钛质部分听骨链移植假体重建听骨链。术后患者立即体会到头部向上冲的感觉,声音诱发眩晕、耳闷、自声增强、耳鸣症状消失;左侧头部知觉恢复正常,右侧头部知觉部分恢复,听力提高,视觉定位好,视物清晰。术后14天左侧4kHz骨导听阈恢复20dB,但全频气骨导差较术前增大。结论微创的圆窗和卵圆窗加固术对撞击伤导致的上半规管裂综合症治疗效果明显。

关键词：半规管裂眩晕圆窗卵圆窗手术

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Clinically relevant human temporal bone measurements using novel high-resolution cone-beam CT

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Journal of Otology 2017年第1期12卷 9-17页

作者： Jing Zou Jaakko Laahelma Antti Arnisalo Ilmari Pyykko Department of Otolaryngology-Head and Neck Surgery Center for Otolaryngology-Head & Neck Surgery of Chinese PLA Changhai Hospital Second Military Medical University Shanghai China Hearing and Balance Research Unit Field of Oto-laryngology School of Medicine University of Tampere Tampere Finland Planmeca Oy Helsinki Finland Department of Otorhinolaryngology-Head and Neck Surgery Helsinki University Central Hospital Helsinki Finland

Objective: To test the feasibility of measuring fine temporal bone structures using a newly established cone-beam computed tomography(CBCT)system.Materials and methods: Six formalin-fixed human cadaver temporal bones were imaged using a high-resolution CBCT system that has 900 frames and copper t aluminum filtration. Fine temporal bone structures, including those of the facial nerve canal and vestibular structures, were identified and measured.Results: The fine structures of the middle ear, including the tympanic membrane, tendon of the tensor tympani, cochleariform process of the semicanal of the tensor tympani, pyramidal eminence, footplate of the stapes, full path of the facial nerve within the temporal bone, supralabyrinthine space, semicircular canals, pathway of the subarcuate canal, and full path of the vestibular aqueduct, were clearly demonstrated. The vestibular aqueduct has a midpoint width of 0.4 ± 0.0 mm and opercular width of 0.5 ± 0.1 mm(mean ± SD). The length of the internal acoustic meatus was 10.6 ± 1.2 mm(mean ± SD), and the diameter of the internal acoustic meatus was 3.7 ± 0.3 mm(mean ± SD).Conclusion: This novel high-resolution CBCT system has potentially broad applications in the diagnosis of inner ear disease and in monitoring associated pathological changes, surgical planning, navigation for the ear surgery, and temporal bone training.

关键词： CT Temporal bone anatomy Vestibule Facial nerve

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低频旋转乳突振动对正常志愿者听力的影响

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中华耳科学杂志 2015年第1期13卷 110-114页

作者：彭日顺子郑贵亮张青郑宏良邹静中国人民解放军第二军医大学长海医院耳鼻咽喉头颈外科全军耳鼻咽喉头颈外科中心上海200433 Hearing and Balance Research Unit Field of Oto-laryngologySchool of MedicineUniversity of Tampere

目的我们设计了一种新颖的治疗眩晕低频旋转乳突振动设备,本研究是为了评估该设备对听觉系统的安全性。方法选12名无眩晕主诉的志愿者,男性10例,女性2例,年龄23-25岁。将低频振动投放于右侧乳突,分别于振动前、振动后0.5小时、7天、和1... 详细信息

目的我们设计了一种新颖的治疗眩晕低频旋转乳突振动设备,本研究是为了评估该设备对听觉系统的安全性。方法选12名无眩晕主诉的志愿者,男性10例,女性2例,年龄23-25岁。将低频振动投放于右侧乳突,分别于振动前、振动后0.5小时、7天、和1年行纯音听阈检测,分析比较双耳的不同频率气、骨导阈值的变化。结果受试者双耳在低频振动后0.5小时的,右耳(暴露耳)在0.25、0.5、1.0 kHz骨导听阈分别降低了3、5、3 d B,有显著性差异(p<0.05),气导阈移无显著性差异;振动后7天,左耳(对照耳)在0.25、0.5 kHz气导听阈分别提高了3、2 dB,有显著性差异(p<0.05);振动后1年右耳在0.25、0.5、8kHz气导听阈分别降低了6、6、9 dB,在0.25、0.5、1 kHz骨导听阈分别升高了7、3、4 dB,均有显著性差异(p<0.05),左耳在2、4、8 kHz气导听阈分别提高了6、6、10 dB,在0.25、0.5、1、2、4kHz骨导听阈分别升高了7、6、6、8、8 dB,均有显著性差异(p<0.05)。结论振动后0.5小时及7天的听阈变化无规律,且数值小,无临床意义;1年后的左耳听阈升高6-10 dB,右耳低频气导听阈降低,低频骨导听阈提高,不符合振动引起的特异性改变,因此,该治疗眩晕的低频乳突振动设备对听觉系统是安全的。

关键词：振动乳突纯音听阈人类

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Can training extend current guidelines for cochlear implant candidacy?

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Neural Regeneration research 2015年第5期10卷 718-720页

作者： Amal Isaiah Douglas E.H.Hartley Department of Otorhinolaryngology-Head and Neck Surgery University of Maryland School of Medicine National Institute for Health research (NIHR) Nottingham Hearing Biomedical Research Unit Otology and hearing Group Division of Clinical NeuroscienceSchool of MedicineUniversity of Nottingham Medical research Council (MRC) Institute of hearing research

Since their introduction in the 1960s, cochlear implants （CIS） have undergone several transformations, ulti- mately positioning themselves as the best-performing neural prosthesis available today. They have also been recognized as a unique tool for studying the potential protective effects of patterned electrical stimulation on the developing auditory system, with results from animal models often changing the manner in which CIs are used clinically to deliver auditory information to the brain （Moore and Shannon, 2009）. From the development of the first successful commercial single-channel device, they have evolved into multi-channel devices that are part of the national health programmes of several coun- tries. From the limited speech information provided by the early, rudimentary cochlear implants, these devices are now in a position to deliver intelligible speech infor- mation to the auditory system, largely due to advances in signal processing. Concerted efforts from several dis- ciplines, including engineering, acoustics, neurobiology and otolaryngology have ensured that the continued development of CI technology has resulted in signifi- cant benefits to individuals with profound sensorineural hearing loss.

关键词： Can training extend current guidelines for cochlear implant candidacy CI

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