蝮蛇抗栓酶治疗特发性突发性感音神经性耳聋的临床研究

我院自1991年3月至1992年11月底共收治特发性突发性感音神经性耳聋(突聋)80例,随机分成治疗组和对照组。治疗组40例,44耳,经蝮蛇抗栓酶治疗,治愈率47.7%,有效率81.8%。对照组40例,48耳,经用低分子右旋糖酐、丹参、病毒唑等药物综合治疗,治愈率25%,有效率50%,治愈率及有效率,治疗组明显高于对照组,经统计学处理,有显著性差异(P<0.05,P<0.01)。据血液流变学资料分析,治疗组治疗后全血低切粘度,高切粘度等五个指标明显下降。研究表明,蝮蛇抗栓酶治疗突聋,疗效高,无明显毒副作用,为治疗突聋开辟了新途径。     

双侧突发性耳聋疗效的影响因素分析

目的:探讨影响双侧突发性耳聋疗效的因素。方法:回顾性分析2011年2月至2013年5月我科收治的24例(48耳)双侧突发性耳聋的病例资料。其中,男性18例(75.0%),女性6例(25.0%)。年龄14-72岁,平均年龄49.3岁。按照听力曲线分型,低中频下降型0耳(0.0%),中高频下降型16耳(33.3%),平坦型18耳(27.5%),全聋型14耳(29.2%)。分析和比较具有不同听力曲线分型、伴发症状、年龄、伴发疾病、听力损失程度、发病至干预时间的双侧突发性耳聋患者总有效率的差异。结果:具有不同听力曲线类型、发病至干预时间、听力损失程度以及是否伴有高血压、糖尿病、高血脂、眩晕症状的双侧突发性耳聋患者的总有效率比较差异均无统计学意义(P0.05)。伴发耳鸣的双侧突发性聋患者治疗总有效率显著高于不伴发耳鸣患者,差异有统计学意义(P0.05)。年龄≤60岁的双侧突发性耳聋患者的治疗总有效率显著高于年龄60岁者(P0.05)。结论:伴发耳鸣、年龄小于60岁的双侧突发性耳聋患者的治疗效果相对较好,而听力曲线类型、听力损失程度、发病至干预时间、是否伴发眩晕症状与其治疗效果均无关。     

耳聋易感基因——间隙连接蛋白26基因

耳聋易感基因——间隙连接蛋白２６基因高琳童坦君（北京医科大学生物化学与分子生物学系,北京１０００８３关键词耳聋易感基因间隙连接蛋白２６基因耳聋和听力损伤是常见的遗传性感觉障碍,大约影响０．１％的儿童。近年已发现一些基因突变与Ｗａａｒｄｅｎｂｕｒｇ综合...     

利用成体干细胞治疗糖尿病

糖尿病是一类严重的代谢疾病, 正危害着世界上越来越多人口的健康。胰岛移植是一种治疗糖尿病的有效方法,却因供体缺乏和移植后免疫排斥问题制约了其广泛应用。干细胞为具有强增殖能力和多向分化潜能的细胞, 是利用细胞替代疗法治疗重大疾病的细胞来源之一, 其中成体干细胞因不存在致瘤性及伦理道德问题而被人们寄予厚望。成体胰腺干细胞在活体损伤及离体培养条件下均能产生胰岛素分泌细胞, 肝干细胞、骨髓干细胞和肠干细胞等在特定离体培养条件下或经过遗传改造后也均可产生胰岛素分泌细胞, 将这些干细胞来源的胰岛素分泌细胞移植到模型糖尿病小鼠中可以治疗糖尿病。因而, 成体干细胞可以为细胞替代疗法治疗糖尿病提供丰富的胰岛供体来源。     

关于不同民族耳聋人群耳聋基因常见突变的筛查分析

目的:分析不同民族(即维吾尔族、汉族、哈萨克族、回族)耳聋人群耳聋基因常见突变的一般特点。方法:选取4个不同民族共计714例耳聋患者(全部属于非综合征性耳聋患者),利用DNA技术对其耳聋基因突变进行分析。结果:在常见耳聋基因检出率方面,汉族为30.83%,哈萨克族为20.00%,回族为16.00%,维吾尔族为12.50%;235delC是汉族、维吾尔族、回族耳聋患者常见突变,35delG是维吾尔族、哈萨克族耳聋患者常见突变,IVS7-2AG是汉族耳聋患者常见突变,187delG是维吾尔族耳聋患者中第一次检测到的病理性突变。结论:在耳聋基因突变方面,4个民族表现出不同的特点,存在一定的差异。     

干细胞与心肌细胞替代治疗

胚胎干细胞及来源于骨髓、骨骼肌、血管、肝脏、皮肤、脂肪等组织器官的成体干细胞均有多向分化潜能。胚胎干细胞可分化为3个胚层的所有组织细胞。成体干细胞具有可塑性和转分化的潜能。在一定条件下,这些干细胞可被诱导分化为心肌细胞。成年心脏可能存在心肌干细胞,具有增殖和分化为包括跳动性心肌细胞的多种细胞的潜能。因此,干细胞可用于心肌细胞替代治疗,以替代死亡的心肌细胞,改善心脏功能,防治心肌梗塞后心衰、减少心肌重构等症状。本文对干细胞治疗心肌梗塞有关进展及问题作一综述。     

高压氧和丹参粉针剂治疗突发性耳聋临床体会

目的 探讨高压氧和丹参粉针剂治疗突发性耳聋的临床意义.方法 将125例突发性耳聋患者随机分为两组,治疗组63例(79耳)采用高压氧和丹参粉针剂治疗,对照组62例(75耳)采用丹参粉针剂治疗.两组疗程结束观察对比疗效.结果 治疗后治疗组听力恢复痊愈19耳,显效28耳,有效25耳,无效7耳,总有效率91.1%;对照组听力恢复痊愈10耳,显效20耳,有效26耳,无效19耳,总有效率为74.7%.两组疗效经Ridit分析,u=2.796,P<0.01,有非常显著性差异.结论 高压氧和丹参粉针剂治疗突发性耳聋可收到明显的疗效.     

干细胞和产前治疗

干细胞特殊的生物性质为产前治疗的研究和应用带来了新的希望。近年来,借助干细胞进行的产前治疗的基础研究进展迅速,为早日在临床广泛开展产前治疗提供了大量有益的参考和指导。本文就这方面的研究进展作一综述。 Stem Cells and Prenatal Therapy WANG Mo-lin,HUANG Shu-zhen Shanghai Institute of Medical Genetics,Shanghai Children Hospital,Shanghai 200040,China Abstract:The special biological properties of stem cells bring us new hope for the research and application of prenatal therapy.The basic reseach of prenatal therapy utilizing stem cells developed quickly,providing reference and direction for clinical therapy.This review is mainly related to the progress in this field in recent years. Key words：stem cell;prenatal therapy     

豚鼠Ⅰ型前庭毛细胞胆碱能受体通道特性

本文旨在探讨豚鼠Ⅰ型前庭毛细胞上有无胆碱能受体存在,并对其相应的离子通道特性进行研究.应用全细胞膜片钳技术检测急性分离的豚鼠Ⅰ型前庭毛细胞对乙酰胆碱(acetylcholine, ACh)的反应.结果显示,7.5%(21/279)的Ⅰ型前庭毛细胞对10～1000μmol/L ACh敏感,引发明显的外向电流.该电流对ACh的反应呈浓度依赖性,半数激活浓度(EC50)为(63.78±2.31)μmol/L,但该电流为非电压依赖性.在-50mV钳制电压和正常细胞外液中,100μmol/L ACh激活一持久缓慢的外向电流,电流幅值为(170±15)pA,该电流幅值依赖于胞外钙离子浓度,可被胞外给予的钙依赖性钾通道拮抗剂TEA阻断.Ⅰ型前庭毛细胞的再次激活时间不小于1min.长时间暴露在ACh的情况下,受体离子通道不会发生自发性关闭.以上结果提示,部分豚鼠Ⅰ型前庭毛细胞上存在胆碱能受体,胞外给予ACh可激活一持久缓慢的外向电流,其胆碱能受体通道对于ACh的作用呈浓度依赖性和外钙依赖性、非电压依赖性或失敏性.本研究结果对于阐明前庭传出神经的功能及其作用机制,证实并揭示Ⅰ型前庭毛细胞上存在传出神经递质受体以及日后临床指导眩晕疾病的康复治疗具有重要的意义.     

Morin hydrate promotes inner ear neural stem cell survival and differentiation and protects cochlea against neuronal hearing loss

We aimed to investigate the effect of morin hydrate on neural stem cells (NSCs) isolated from mouse inner ear and its potential in protecting neuronal hearing loss. 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) and bromodeoxyuridine incorporation assays were employed to assess the effect of morin hydrate on the viability and proliferation of in vitro NSC culture. The NSCs were then differentiated into neurons, in which neurosphere formation and differentiation were evaluated, followed by neurite outgrowth and neural excitability measurements in the subsequent in vitro neuronal network. Mechanotransduction of cochlea ex vivo culture and auditory brainstem responses threshold and distortion product optoacoustic emissions amplitude in mouse ototoxicity model were also measured following gentamicin treatment to investigate the protective role of morin hydrate against neuronal hearing loss. Morin hydrate improved viability and proliferation, neurosphere formation and neuronal differentiation of inner ear NSCs, and promoted in vitro neuronal network functions. In both ex vivo and in vivo ototoxicity models, morin hydrate prevented gentamicin‐induced neuronal hearing loss. Morin hydrate exhibited potent properties in promoting growth and differentiation of inner ear NSCs into functional neurons and protecting from gentamicin ototoxicity. Our study supports its clinical potential in treating neuronal hearing loss.     

Hidden hearing loss is associated with loss of ribbon synapses of cochlea inner hair cells

The present study aimed to observe the changes in the cochlea ribbon synapses after repeated exposure to moderate-to-high intensity noise. Guinea pigs received 95 dB SPL white noise exposure 4 h a day for consecutive 7 days (we regarded it a medium-term and moderate-intensity noise, or MTMI noise). Animals were divided into four groups: Control, 1DPN (1-day post noise), 1WPN (1-week post noise), and 1MPN (1-month post noise). Auditory function analysis by auditory brainstem response (ABR) and compound action potential (CAP) recordings, as well as ribbon synapse morphological analyses by immunohistochemistry (Ctbp2 and PSD95 staining) were performed 1 day, 1 week, and 1 month after noise exposure. After MTMI noise exposure, the amplitudes of ABR I and III waves were suppressed. The CAP threshold was elevated, and CAP amplitude was reduced in the 1DPN group. No apparent changes in hair cell shape, arrangement, or number were observed, but the number of ribbon synapse was reduced. The 1WPN and 1MPN groups showed that part of ABR and CAP changes recovered, as well as the synapse number. The defects in cochlea auditory function and synapse changes were observed mainly in the high-frequency region. Together, repeated exposure in MTMI noise can cause hidden hearing loss (HHL), which is partially reversible after leaving the noise environment; and MTMI noise-induced HHL is associated with inner hair cell ribbon synapses.     

Stem cells as therapy for hearing loss

One of the greatest challenges in the treatment of inner-ear disorders is to find a cure for the hearing loss that is caused by the loss of cochlear hair cells or spiral ganglion neurons. The recent discovery of stem cells in the adult inner ear that are capable of differentiating into hair cells, as well as the finding that embryonic stem cells can be converted into hair cells, raise hope for the future development of stem-cell-based treatment regimens. Here, we propose different approaches for using stem cells to regenerate the damaged inner ear and we describe the potential obstacles that translational approaches must overcome for the development of stem-cell-based cell-replacement therapies for the damaged inner ear.     

Celastrol enhances Atoh1 expression in inner ear stem cells and promotes their differentiation into functional auditory neuronal-like cells

We aimed to investigate the beneficial effect of Celastrol on inner ear stem cells and potential therapeutic value for hearing loss. The inner ear stem cells were isolated and characterized from utricular sensory epithelium of adult mice. The stemness was evaluated by sphere formation assay. The relative expressions of Atoh1, MAP-2 and Myosin VI were measured by RT-PCR and immunoblotting. The up-regulation of MAP-2 was also analysed with immunofluorescence. The in vitro neuronal excitability was interrogated by calcium oscillation. The electrophysiological property was determined by inward current recorded on patch clamp. Our results demonstrated that Celastrol treatment significantly improved the viability and proliferation of mouse inner ear stem cells, and facilitated sphere formation. Moreover, Celastrol stimulated differentiation of mouse inner ear stem cells to neuronal-like cells and enhanced neural excitability. Celastrol also enhanced neuronal-like cell identity in the inner ear stem cell derived neurons, as well as their electrophysiological function. Most notably, these effects were apparently associated with the upregulation of Atoh1 in response to Celastrol treatment. Celastrol showed beneficial effect on inner ear stem cells and held therapeutic promise against hearing loss.     

Evidence for multiple,developmentally regulated isoforms of Ptprq on hair cells of the inner ear

Ptprq is a receptor‐like inositol lipid phosphatase associated with the shaft connectors of hair bundles. Three lines of evidence suggest Ptprq is a chondroitin sulfate proteoglycan: (1) chondroitinase ABC treatment causes a loss of the ruthenium‐red reactive, electron‐dense particles associated with shaft connectors, (2) chondroitinase ABC causes an increase in the electrophoretic mobility of Ptprq, and (3) hair bundles in the developing inner ear of wild‐type mice, but not those of Ptprq^?/? mice, react with monoclonal antibody (mAb) 473‐HD, an IgM that recognizes the dermatan‐sulfate‐dependent epitope DSD1. Two lines of evidence indicate that there may be multiple isoforms of Ptprq expressed in hair bundles. First, although Ptprq is expressed throughout the lifetime of most hair cells, hair bundles in the mouse and chick inner ear only express the DSD1 epitope transiently during development. Second, mAb H10, a novel mAb that recognizes an epitope common to several avian inner‐ear proteins including Ptprq, only stains mature hair bundles in the extrastriolar regions of the vestibular maculae. MAb H10 does not stain mature hair bundles in the striolar regions of the maculae or in the basilar papilla, nor does it stain immature hair bundles in any organ. Three distinct, developmentally regulated isoforms of Ptprq may therefore be expressed on hair bundles of the chick inner ear. Hair bundles in the mature chick ear that do not express the H10 epitope have longer shaft connectors than those that do, indicating the presence or absence of the H10 epitope on Ptprq may modulate the spacing of stereocilia. © 2010 Wiley Periodicals, Inc. Develop Neurobiol 71: 129‐141, 2011     

Generating high-fidelity cochlear organoids from human pluripotent stem cells

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RIPOR2-mediated autophagy dysfunction is critical for aminoglycoside-induced hearing loss

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Therapeutic potential of neurotrophins for treatment of hearing loss

Degeneration of spiral ganglion neurons (SGNs) and hair cells in the cochlea induced by aging, injury, ototoxic drugs, acoustic trauma, and various diseases is the major cause of hearing loss. Discovery of growth factors that can either prevent SGN and hair-cell death or stimulate hair-cell regeneration would be of great interest. Studies over the past several years have provided evidence that specific neurotrophins are potent survival factors for SGNs and protect these neurons from ototoxic drugs in vitro and in vivo. Current research focuses more on understanding the mechanism of hair-cell regeneration/differentiation and identification of growth factors that can stimulate hair-cell regeneration. SGNs are required to relay the signal to the central nervous system even when a cochlear implant is used to replace hair-cell function or in the case that cochlear sensory epithelium can be stimulated to regenerate new hair cells successfully. Therefore, neurotrophins may have their therapeutic value in prevention and treatment of hearing impairment.     

The expression of PHB2 in the cochlea: Possible relation to age-related hearing loss

Age-related hearing loss (ARHL) is the most prevalent sensory deficit in the elderly, but its mechanism remains unclear. Scaffold protein prohibitin 2 (PHB2) has been widely involved in aging and neurodegeneration. However, the role of PHB2 in ARHL is undeciphered to date. To investigate the expression pattern and the role of PHB2 in ARHL, we used C57BL/6 mice and HEI-OC1 cell line as models. In our study, we have found PHB2 exists in the cochlea and is expressed in hair cells, spiral ganglion neurons, and HEI-OC1 cells. In mice with ARHL, mitophagy is reduced and correspondingly the expression level of PHB2 is decreased. Moreover, after H₂O₂ treatment the mitophagy is activated and the PHB2 expression is increased. These findings indicate that PHB2 may exert an important role in ARHL through mitophagy. Findings from this study will be helpful for elucidating the mechanism underlying the ARHL and for providing a new target for ARHL treatment.     

Cell-type identity of the avian cochlea

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