Adenoviral-mediated Hath1-EGFP gene transfer into guinea pig cochlea through intact round window membrane

Objective To study expression of adenoviral-mediated Hath1-EGFP gene in the guinea pig cochlea after transfer through intact round window membrane(RWM), and to assess its effects on hearing. Methods Twenty adult guinea pigs were used, of which: 12 were surgically inoculated with Ad-Hath1-EGFP in the bony groove of round window niche, and 8 with artificial perilymph. Auditory brainstem response(ABR) thresholds were determined in all animals before and 5 days after surgery. On post-surgery day 5 and day 14, animals were sacrificed and whole mounts of cochlea and frozen sections were examined. Results ABR tests showed no significant change of hearing after the surgery. Strong fluorescence staining in the cochleae was seen in Ad-Hath1-EGFP groups. The highest levels of gene expression were seen in the post-surgery day 5 group with little decrease on post-surgery day 14.The contralateral cochlea and those in the control groups were free of fluorescence staining. Conclusion The transgenic Hath1-EGFP can be effectively delivered into the inner ear through intact RWM, in an atraumatic manner.

Mechanical model of round window membrane under reverse excitation

According to the vibration characteristics of the round window, a mechani- cal model of a round window membrane is established. The Euler equation of the round window and the complementary boundary conditions are derived by the variational prin- ciple. Combined with the Bessel function, an analytical solution of the round window displacement is obtained by MATHEMATICA. Combined with clinical characteristics of round window membrane lesion, the effect of sound transmission due to thickening of the round window membrane caused by the otitis media, shrinkage of the round window membrane area caused by otosclerosis, and hardening of the round window membrane itself is analyzed. The results show that with thickening of the round window membrane, the displacement of the round window membrane is decreased. In the meantime, with hardening of the round window membrane and shrinkage of the membrane area, the max- imum displacement Of the round window membrane is gradually reduced, leading to a decrease in sound transmission. Thus, the analyticM analysis can avoid interference of environment and the technical level of personnel, and it can evaluate transmission per- formance of the round window membrane efficiently, providing a theoretical basis for the reverse excitation of artificial prosthesis.

Permeability of round window membrane and its role for drug delivery:our own findings and literature review

We investigated the pharmacokinetics of caroverine in the perilymph,cerebrospinal fluid and plasma after systemic and local administrations in guinea pigs by using high-performance liquid chromatography.Auditory brainstem responses were measured to evaluate auditory functional effect.The results showed that local application was a both safe and efficient method.We further reviewed literature and pinpointed that the round window is effectively local drug delivery means for future inner ear treatment.

In vitro permeability of round window membrane to transforming dexamethasone with delivery vehicles——a dosage estimation

Background In recent years the interest of sustained drug delivery into inner ear is promising, at the same time a great deal of novel oral drugs using biodegradable vehicles have been produced to achieve sustained drug release. The aim of this study was to use biodegradable vehicles to release dexamethasone in the round window membrane application. Methods Dexamethasone gels composed of alginate and chitin were prepared and the release-permeating profiles were studied using a reproducible in vitro apparatus. A longer-period time course was simulated using the parameters acquired in this study. The data obtained in this study was compared with those of other studies in intratympanic drug delivery, and an appropriate initial dosage was extrapolated. Results The combination of alginate and chitin could efficiently restrict dexamethasone diffusion and the time course suggested a sustained drug concentration within 24 hours. A higher initial dosage was estimated to achieve a stable therapeutic concentration in vivo. Conclusion The combination of alginate and chitin could be used as vehicle for sustained release of dexamethasone in intratympanic application.

Application of intraoperative round window electrocochleography for screening the patients with auditory neuropathy

Background Most patients with auditory neuropathy （AN） could receive good even the best effects after cochlear implantation. How to diagnose AN objectively and accurately is very important. In this study, we screened the patients with AN according to the presence or absence of compound action potential （CAP） of intraoperative round window electrocochleography （RW ECochG）. Methods Intraoperative RW ECochG was performed on 32 patients with profound sensorineural deafness, who had normal cochlea during cochlear implantation surgery under general anesthesia in the standard operating room. The cochlear microphonic （CM） and CAP of RW ECochG was observed and recorded. Results The presence of CM but the absence of CAP of RW ECochG occurred in 12 among the 32 patients. They were suspected to suffer from AN. The rest patients who had CM and CAP of RW ECochG were thought not to suffer from AN. Conclusion Application of intraoperative RW ECochG during the cochlear implantation surgery may objectively and accurately screen the patients with AN, and can give a meaningful clue for implanted device working.

The impact of round window vs cochleostomy surgical approaches on interscalar excursions in the cochlea:Preliminary results from a flat-panel computed tomography study

Objective:To evaluate incidence of interscalar excursions between round window (RW) and cochleostomy approaches for cochlear implant (CI) insertion. Methods:This was a retrospective case-comparison. Flat-panel CT (FPCT) scans for 8 CI users with Med-El standard length electrode arrays were collected. Surgical technique was identified by a combination of operative notes and FPCT imaging. Four cochleae underwent round win-dow insertion and 4 cochleae underwent cochleostomy approaches anterior and inferior to the round window. Results:In our pilot study, cochleostomy approaches were associated with a higher likeli-hood of interscalar excursion. Within the cochleostomy group, we found 29% of electrode contacts (14 of 48 electrodes) to be outside the scala tympani. On the other hand, 8.5%of the electrode contacts (4 of 47 electrodes) in the round window insertion group were extra-scalar to the scala tympani. These displacements occurred at a mean angle of occur-rence of 364? ? 133?, near the apex of the cochlea. Round window electrode displacements tend to localize at angle of occurrences of 400? or greater. Cochleostomy electrodes occurred at an angle of occurrence of 19?e490?.

Radiologic anatomy of the round window relevant to cochlear implantation and inner ear drug delivery

Objective:To determine anatomic relationships and variation of the round window membrane to bony surgical landmarks on computed tomography.Study design:Retrospective imaging review.Methods:100 temporal bone images were evaluated.Direct measurements were obtained for membrane position.Vector distances and angulation from umbo and bony annulus were calculated from image viewer software coordinates.Results:The angle of round window membrane at junction with cochlear basal turn was(42.1±8.6)°.The membrane’s position relative to plane of the facial nerve through facial recess was(14.7±5.2)°posterior from a reference line drawn through facial recess to carotid canal.Regarding transtympanic drug delivery,the round window membrane was directed 4.1 mm superiorly from the inferior annulus and 5.4 mm anteriorly from the posterior annulus.The round window membrane on average was angled superiorly from the inferior annulus(77.1±27.9)°and slightly anteriorly from the posterior annulus(19.1±11.1°).The mean distance of round window membrane from umbo was 4 mm and posteriorly rotated 30°clockwise from a perpendicular drawn from umbo to inferior annulus towards posterior annulus.Together,these measurements approximate the round window membrane in the tympanic membrane’s posteroinferior quadrant.Conclusions:These radiologic measurements demonstrate normal variations seen in round window anatomy relative to facial recess approach and bony tympanic annulus,providing a baseline to assess round window insertion for cochlear implantation and outlines anatomic factors affecting transtympanic drug delivery.

圆窗膜挑开前后豚鼠听功能变化研究

目的探讨圆窗膜挑开前后健康豚鼠听功能的变化。方法选取健康豚鼠30只(60耳),吸入异氟烷麻醉后打开听泡挑开圆窗膜挑开前后分别行听性脑干反应(ABR)、耳蜗电图(electrocochleogram,ECochG)、电诱发复合动作电位(electrically evoked compound action potentials,ECAP)及电诱发听性脑干反应(electrically evoked auditory brainstem responses,EABR)检测,进行统计学分析。结果豚鼠54耳记录到分化良好且稳定的以III波为主的ABR、ECochG、ECAP及EABR波形。圆窗膜挑开前后ABR阈值分别为36.67±7.76 dB SPL、98.81±10.74 dB SPL,二者之间有显著差异(P<0.05);ECochG中CAP阈值分别为28.73±9.72 dB SPL、68.48±11.21 dB SPL,二者之间有显著差异(P<0.05);ECAP阈值分别为0.35±0.11 mA、0.46±0.13 mA,二者之间有显著差异(P<0.05);EABR阈值分别为0.21±0.05 mA、0.30±0.07 mA,二者之间有显著差异(P<0.05)。结论圆窗膜挑开前后健康豚鼠的听功能出现明显变化,表现为听力下降。

圆之缘——中国传统建筑中的圆门窗探源

圆形门和圆形窗是中国传统建筑中典型的形式语言和象征符号,它们随处可见甚至到了泛滥之态,然而这种圆形母题的“中国式样”究竟源自何时、如何发展、意义何在尚未有公论。通过梳理历史文献和相关学者论述,结合传统造型、传统绘画、传统园林建筑等具体案例,试图厘清圆门窗的发展源流、形式特点,以及其在中国传统建筑中的空间和文化意义。

融合多语义特征的精读式文档级事件抽取

为解决文档级事件抽取任务依赖实体识别、忽略先验语义和参数分散的问题,提出一种融合多语义特征的精读式抽取方法。结合“三阶段”阅读特点,根据事件与角色交互、角色类型及释义特征构建外部语义模板,提出窗口切分算法切割文档语义;基于预训练模型BERT融合外部与窗口语义;多轮精读文档避免实体依赖,设计记忆网络对精读结果建模,完成跨句定位参数和事件路径扩展。引入噪声扰动防止模型过拟合。实验结果表明,该模型性能优于当前主流方法,验证了其可行性和有效性。

初压力控制式圆窗激振压电作动器设计与优化

针对临床上所用的圆窗激振人工中耳不是针对该激振方式设计,存在术后补偿性能个体差异大、性能不稳定、增益值达不到理论值的问题,设计了一款作动端与圆窗膜尺寸匹配、初始压力可控的圆窗激振压电作动器。首先,结合人耳解剖结构,设计了作动器的机械组成结构及宏观尺寸;其次,对弯张放大器进行受力分析,采用粒子群算法对弯张放大器进行优化设计,以获得最优输出位移放大倍数;再次,构建了压电作动器-人耳耦合力学模型,分析了支撑弹簧横截面积与压电叠堆层数对作动器听损补偿性能的影响,确定了该设计参数;最后,根据确定的设计尺寸制造了压电作动器样机,搭建了激光测振试验台,对压电作动器的动态特性进行了测试。试验结果表明,所设计的圆窗激振式压电作动器作用在圆窗膜上的初始压力可控,且具有工作频带宽(100~10000 Hz)、谐波失真低(THD≤0.29%)的优点。该压电作动器适用于圆窗激振的听力损伤补偿,为混合性听力损伤的临床治疗提供一种新的方案。

面神经垂直段遮窗患者人工耳蜗植入

目的 报告面神经垂直段遮窗患者人工耳蜗植入(cochlear implantation, CI)方法。方法 回顾性分析2015年1月至2021年1月收治的5例面神经垂直段遮窗的重度或极重度聋患者的临床资料,包括病史、听力资料、影像学资料、手术方法等。结果 5例面神经垂直段遮窗患者中,4例为面神经垂直段完全遮挡圆窗,调整患者体位及显微镜角度仍无法窥及圆窗,选择面后入路行人工耳蜗电极植入;1例为面神经垂直段部分遮挡圆窗,调整患者体位及显微镜角度可见部分圆窗,选择将骨性外耳道后壁磨低,低于鼓乳裂水平,直至充分暴露圆窗后行人工耳蜗电极植入。5例患者均顺利植入电极,术中神经反应遥测均引出,术后未见面神经麻痹、外耳道后壁塌陷、平衡障碍等并发症发生。结论 重度或极重度聋患者人工耳蜗植入术中发现面神经垂直段遮挡圆窗时可根据遮窗程度选择不同的手术方式,面神经垂直段完全遮窗可选择面后入路,部分遮窗可选择磨低骨性外耳道后壁完成人工耳蜗电极植入。

圆中园——从圆门(窗)管窥中国园林的符号与空间

圆形门和圆形窗是中国传统园林建筑中典型的形式符号和空间语言,一方面其抽象的几何原型蕴含着极强的理性和哲学意味,另一方面与月亮的形式关联又将之引向诗情画意的移情想象。圆洞门(窗)因其特殊形态成为了中国园林中无可比拟的一种设计语汇,承载了“如画视觉”和“入画行为”的双重属性。通过解析传统园林中具体的圆门(窗)案例,探究其形式渊源、造型操作、符号特征和空间意义,探讨在现代建筑中重构和转译这种古典语汇的可能性。

基于往返时延梯度的多路径拥塞控制算法

为更好利用有限的网络带宽资源,提高带宽利用率,提出一种利用往返时延梯度精确感知带宽变化的多路径拥塞控制算法。根据往返时延的大小反馈网络拥塞程度,将拥塞程度量化为时延梯度作为拥塞窗口的控制参数;为保证链路公平,利用往返时延估计链路带宽,经迭代分配带宽,给出公平的资源分配方法。在NS-3上进行仿真,其结果表明,多路径流的吞吐量较单路径流明显提高,保证了链路分配的公平,动态环境下的响应时间较同类算法有所减小。该算法进一步提高了网络带宽的利用率。

鼓室灌注地塞米松治疗难治性突发性感音神经性聋临床分析

目的观察和比较鼓膜穿刺、鼓膜置管和圆窗置管微泵灌注地塞米松3种方法治疗难治性突发性感音神经性聋的疗效。方法55例常规方法治疗无效的突聋患者作为研究对象,其中圆窗置管微泵灌注用药治疗21例(置管组),每次2.5mg/0.5ml,维持1小时,每天两次,连续给药7天,总剂量35mg;鼓膜穿刺注药23例(穿刺组),首次剂量为2.5mg,此后,每2天重复注药1次(每次2.5mg),共4次,总剂量10mg;鼓膜切开置管滴药11例(滴药组),首次剂量为0.5%地塞米松0.5ml,经通气管滴入鼓室,每天重复滴药2次(每次2.5mg),共7天,总剂量32.5mg。同期常规方法治疗无效的32例突聋患者,且拒绝鼓室用药者随访作为对照(对照组),比较各组听力恢复及并发症情况。4组治疗前听力无显著差异(P>0.05)。结果治疗完成后1月纯音测听检查:置管组、穿刺组和滴药组平均PTA分别提高9dB、8.6dB和1.7dB,前2组明显高于对照组1.4dB(P<0.05),置管组8例(38.1%)听力改善约15～56dB,无效13例;穿刺组8例(34.8%)听力改善约16～54dB,无效15例;滴药组1例(9.1%)听力改善约26dB,无效10例;对照组3例(9.4%)听力改善约15～36dB,无效29例。结论鼓室灌注地塞米松治疗难治性突聋方法安全有效,为用常规方法治疗无效的突聋患者,提供了再次治疗的机会。

与人工耳蜗植入术相关的面神经垂直段应用解剖

目的 通过观测面神经垂直段解剖 ,了解与圆窗龛的关系 ,为人工耳蜗植入手术中避免面神经损伤提供参考。方法 通过对 12个成人颞骨标本解剖 ,模拟人工耳蜗植入术 ,观察和测量面神经垂直段位置与圆窗龛关系。结果 圆窗龛上缘至面神经垂直段距离 5 .49± 1.0 76mm ,圆窗上缘至砧骨短脚 5 .0 7± 2 .0 2mm ,圆窗龛平面面神经至鼓索神经距离 2 .2 5± 0 .3 8mm ,圆窗龛平面面神经垂直段至后半规管距离 2 .41± 0 .46mm。圆窗龛全貌能暴露者 7例 ,前部部分暴露 4例 ,有一例圆窗龛因面神经垂直段影响未能显示 ,未见面神经垂直段有分成两支的情况。结论 面神经垂直段前置将影响圆窗龛暴露 。

腺病毒携带EGFP基因经完整圆窗膜转导豚鼠耳蜗的实验研究

目的研究腺病毒携带目的基因经完整圆窗膜途径耳蜗转导的可行性及安全性,为内耳基因治疗提供实验基础和理论依据。方法20只白色红目豚鼠,术前及术后分别行听性脑干反应(ABR)检查。实验组(12只)以重组腺病毒携带的增强型绿色荧光蛋白基因(enhanced green fluorescent protein,EGFP),对照组(8只)以人工外淋巴液注入豚鼠圆窗龛内。分别于术后5天、14天取双侧耳蜗标本做基底膜铺片,耳蜗冰冻切片观察。结果于圆窗龛内注入腺病毒携带目的基因的转导方法对听力无明显影响。转染耳蜗及对侧耳蜗内目的基因呈广泛表达。5天组表达产物最高,14天组逐渐降低。对照组耳蜗未见EPFP表达。结论于圆窗龛内注入腺病毒携带目的基因转导的方法对耳蜗无明显毒害作用,且能够将目的基因成功转导至双侧耳蜗组织并广泛表达。

人工耳蜗植入术鼓阶入口定位的相关解剖研究

目的通过对人工耳蜗植入手术相关的后鼓室及上鼓室解剖结构进行观察、测量,为人工耳蜗植入手术中顺利找到并准确定位鼓阶入口提供理论参考。方法对20侧成人颞骨标本进行解剖,模拟人工耳蜗植入术,在手术显微镜下观察、测量与人工耳蜗植入手术相关的解剖数据。结果砧骨短脚至圆窗龛之间的距离为(5.91±0.29)mm;镫骨头至圆窗龛之间的距离为(2.11±0.18)mm;面神经垂直段至圆窗龛之间的距离为(6.70±0.19)mm;锥隆起至圆窗膜前缘之间的距离为(2.22±0.21)mm;镫骨头至圆窗膜下缘之间的距离为(2.16±0.14)mm;鼓阶入口与卵圆窗最近距离为(2.12±0.19)mm;匙状突至圆窗龛之间的距离为(3.79±0.17)mm;镫骨头至耳蜗第二回切开点之间距离为(2.25±0.13)mm;锥隆起至耳蜗第二回转切开点之间距离为(2.28±0.20)mm。结论人工耳蜗植入手术中切开耳蜗底回的位置位于锥隆起前下方约2.22 mm处;切开耳蜗第二回的位置位于锥隆起前上方约2.28 mm处;根据病人不同情况,为术中选择不同的鼓阶切开点提供了参考。

耳后入路圆窗膜显微注射小鼠耳蜗基因转染新途径的研究

目的研究腺病毒携带目的基因经小鼠耳后入路圆窗膜显微注射途径耳蜗转导的可行性,为以小鼠作为动物模型的内耳基因治疗提供实验基础和解剖学依据。方法12只C57BL/6J小鼠分为2组,实验组(8只)以重组腺病毒携带的增强型绿色荧光蛋白基因(enhanced green fluorescent protein,EGFP)、对照组(4只)以人工外淋巴液经耳后入路圆窗膜显微注射注入耳蜗内。分别于术后5、14天取双侧耳蜗标本做基底膜铺片,在激光共聚焦显微镜下观察GFP表达。结果术后动物存活10只(每组死亡1只)。实验组转染后耳蜗底回基底膜及螺旋神经节上目的基因有表达,14天组强于5天组。对照组耳蜗未见荧光表达。结论耳后入路操作简单、损伤小、易于暴露圆窗龛。耳后入路圆窗膜显微注射腺病毒携带目的基因转导的方法能够将目的基因成功转导至耳蜗组织并表达。

圆窗区颞骨切片和CT对照观察

目的 明确圆窗区及其相关结构在耳的横断薄层和在CT上的定位及毗邻关系 ,为该区域病变的影像诊断和手术治疗提供解剖学参考。方法 外观无异常的经 10 %甲醛固定的成人头颅标本 15例 (30侧 ) ,以眦耳线为基线 ,用高分辨率CT扫描 ,获得间隔为 1 0 0mm ,厚度为 1 0 0mm的CT图像 ,扫描后的颅脑标本按原定位截取以耳颞区为中心的组织块 ,常规脱钙、脱水、火棉胶浸胶 ,包埋并按标记切制成厚为 1 0 0mm的连续横断薄层切片 ,肉眼和手术显微镜下观察切片的下表面并扫描照相。标本切片与CT图像对照 ,逐一辨识颞骨内听小骨、骨性半规管、前庭、圆窗、圆窗龛、耳蜗、锥隆起、内耳道、耳蜗水管等结构。结果 颞骨横断CT扫描 ,有 18～ 2 2个层面 ,圆窗和圆窗龛出现层面多为第 10层 (右侧 )和第 11层 (左侧 ) ,圆窗龛前壁厚度平均为右侧 0 92mm和左侧 0 90mm ,龛深平均为右侧 1 89mm和左侧 2 0 4mm ,龛与颈静脉窝间骨壁的平均距离为右侧 2 10mm和左侧 2 39mm。龛前壁厚度、龛深、龛与颈静脉窝骨壁的距离左、右侧差异无显著性 (P >0 0 5 )。结论 耳颞区火棉胶薄层断面标本能良好显示圆窗区及其周围结构的解剖位置和毗邻关系 ,可直接与高分辨率CT扫描图像进行对照研究 ,其结果对耳科疾病的影像诊断及手术治疗有?