骨髓间充质干细胞治疗感音神经性耳聋相关实验技术体系建设概要

感音神经性耳聋是由于内耳感觉细胞的损伤造成的,其治疗一直是耳科医生十分棘手的问题。近年来,利用干细胞修复内耳感觉细胞在国内外大量的研究中取得了诸多重要进展,特别是骨髓间充质干细胞,有易分离、低免疫源性、无致瘤性等优点,极具临床应用价值。但目前国内外各个研究小组从干细胞的制备,诱导到移植内耳的方法均有差异,未形成统一的流程,不利于其学术交流和实验结果大样本收集。本文集中介绍谢鼎华课题组在国家973项目干细胞治疗耳聋的实验技术体系标准制定课题的基础研究方法,并综述目前本领域国际最新动态,初步提出骨髓间充质干细胞治疗感音神经性耳聋的技术方法和质量控制措施的推荐方案,为最终临床安全、规范化运用干细胞治疗耳聋提供依据。     

干细胞与感音神经性耳聋

随着干细胞研究的深入,特别是近年来内耳干细胞的发现,为感音神经性耳聋的治疗带来了希望,本文就内耳干细胞的研究进展以及干细胞在感音神经性耳聋治疗的应用前景作一综述。     

干细胞与感音神经性耳聋

随着干细胞研究的深入,特别是近年来内耳干细胞的发现,为感音神经性耳聋的治疗带来了希望,本文就内耳干细胞的研究进展以及干细胞在感音神经性耳聋治疗的应用前景作一综述。     

感音神经性耳聋的预防及治疗

人类耳蜗有内外两种毛细胞。内毛细胞把外界传人内耳的声信号转换成电信号。外毛细胞对声信号起到协调作用。听觉神经元把电信号进一步传人听觉通道，最后传人听觉中枢。不幸的是，无论毛细胞或听神经元的损伤都可导致永久性不可逆转的感音神经性耳聋。占人类10％以上的成年人群都患有不同程度的感音神经性耳聋，随着世界人1：3的老龄化，耳聋占人类群体的比例会进一步上升。     

干细胞来源及内耳导入途径的研究进展

移植干细胞来源的选择、干细胞定向诱导分化、内耳移植途径的选择及移植后内耳功能恢复状况的评估是干细胞临床应用的研究热点。干细胞种类选择以及移植途径不同是影响内耳移植安全性及内耳功能恢复效果的两个重要因素,也是目前研究干细胞移植治疗耳聋的重点。本文就上述两者对感音神经性耳聋的治疗机制的相关文献进行综述,从而为耳聋传统治疗方案提供更新的指导。     

低频感音神经性聋患者的内耳免疫学探讨

目的 测定抗内耳自身抗体,以研究低频感音神经性耳聋患者与内耳免疫的相关性。方法 通过临床详细询问病史、纯音测听、声导抗测试及ABR测试,选择低频感音神经性聋患者30例做为研究对象。以豚鼠内耳石蜡切片作为抗原,用间接免疫荧光法检测患者血清中的抗内耳抗体。结果 30例患者中有26例血清中抗内耳抗体阳性,阳性率为86.67%,P<0.01有极显著性差异;低频感音神经性聋在青少年组(≤25岁)和女性组呈高发,阳性率均为63.33％(19／30),P<0.05有显著性差异;低频感音神经性聋多为双侧耳聋,少数为单侧耳聋,双侧耳聋阳性率为86.67%(26／30),P<0.01有极显著性差异。结论 自身免疫反应参与了低频感音神经性聋的发病过程;低频感音神经聋与年龄和性别有关;低频感音神经性聋发病多为双侧聋;同时检测患者血清ⅠgM和ⅠgG内耳抗体,可协助诊断。     

骨髓间充质干细胞内耳移植

干细胞内耳移植是近年来治疗感音神经性聋的研究热点,骨髓间充质干细胞具有多方向分化能力、低免疫源性和可以自体移植的优点,在内耳移植治疗上具有一定优势,本文总结骨髓间充质干细胞移植内耳后细胞分布、存活、分化情况以及应用于基因治疗等方面的进展.     

SOX10基因与综合征型耳聋的研究进展北大核心CSCD

SOX10参与神经嵴细胞的发育过程,在调控神经嵴细胞生存和保持多向分化潜能等方面起重要作用,研究表明SOX10基因在人体多个组织与器官中表达。感音神经性耳聋是由于螺旋器、听神经和各级听觉中枢的病变导致声音的感受和神经冲动传导发生障碍引起的耳聋。研究发现SOX10基因与先天性感音神经性耳聋关系密切,尤以综合征型聋为主,该基因影响内耳感觉上皮祖细胞分化及调控相关耳聋基因的表达,针对SOX10基因及蛋白与综合征型耳聋的研究有利于揭示耳聋的分子病因。     

神经干细胞耳蜗移植与感音神经性耳聋基因治疗

神经干细胞具有低免疫原性、自我更新及多潜能分化等特性。此外,神经干细胞可转染神经营养因子基因等目的基因,并能整合于宿主细胞,长期稳定表达外源性基因。因此,神经干细胞可以作为内耳基因治疗的一个理想载体,通过转染神经营养因子基因,并移植于耳蜗,在感音神经性耳聋的治疗中可能具有潜在的应用价值。     

先天性内耳畸形的临床表现及处理

先天性感音神经性聋包括遗传和非遗传内耳或听觉神经系统畸形（损害）而导致的感音神经性聋,也可伴发其他器官或系统畸形,先天性聋中大部分是遗传性的,约半数是严重耳聋。可分为单纯性耳聋及耳聋伴有内耳畸形。先天性感音神经性聋的病因中,CT和MRI所能分辨出的骨性内耳畸形所致者占20%～30%[1],其余为膜性畸形以及细胞水平的病理所致。而先天性内耳畸形临床罕见,极易漏诊误诊。为提高对本病的认识,我们收集确诊的Mondini畸形及大前庭水管综合征各1例临床资料报道如下。     

突发性耳聋的疗效探索

目的 探索突发性耳聋的有效治疗方案。方法 将我科近年来收治的394例突聋患者分为5组。第一组中西医结合治疗40例。在此基础上，第二组加体外反搏治疗44例，第三组加高压氧舱治疗46例，第四组加光量子血液疗法46例；第五组加声信息治疗52例。与之比较相应各组的中西医结合组分别为42例、44例、40例和40例。结果 第一组有效率70．0％，第二组有效率86．4％，第三组有效率89．1％，第四组有效率93．5％，第五组有效率88．5％。第一组与其余4组的疗效差异有显著性意义（P＜0．05）。结论 药物治疗的同时加用各种特殊治疗，均将取得更好的疗效。     

Evaluation of an Active Humidification System for Inspired Gas

ObjectivesThe effectiveness of the active humidification systems (AHS) in patients already weaned from mechanical ventilation and with an artificial airway has not been very well described. The objective of this study was to evaluate the performance of an AHS in chronically tracheostomized and spontaneously breathing patients.MethodsMeasurements were quantified at three levels of temperature (T°) of the AHS: level I, low; level II, middle; and level III, high and at different flow levels (20 to 60 L/minute). Statistical analysis of repeated measurements was performed using analysis of variance and significance was set at a P<0.05.ResultsWhile the lowest temperature setting (level I) did not condition gas to the minimum recommended values for any of the flows that were used, the medium temperature setting (level II) only conditioned gas with flows of 20 and 30 L/minute. Finally, at the highest temperature setting (level III), every flow reached the minimum absolute humidity (AH) recommended of 30 mg/L.ConclusionAccording to our results, to obtain appropiate relative humidity, AH and T° of gas one should have a device that maintains water T° at least at 53℃ for flows between 20 and 30 L/m, or at T° of 61℃ at any flow rate.     

Local interferon therapy for lip carcinoma

In a prospective non-randomized study 21 patients with lower lip squamous cell carcinoma were treated with human natural leukocyte interferon (HNLI). The response rate was measured by a size reduction of more than 25% and was 81%. A complete response rate was considered to be a cure according to histopathological and clinical findings and was 48%. The response rate of six lower lip squamous cell carcinoma cases treated with recombinant interferon alpha 2c was 67% and the complete response rate was 17%. Three patients with basal cell carcinoma of the upper lip were also treated with HNLI. All three patients were cured, as determined by histopathological and clinical findings. These findings indicate that interferon can be a useful alternative therapy for lip carcinoma either with or without surgery.     

Defibrinogenation Therapy for Idiopathic Sudden Sensorineural Hearing Loss in Comparison with High-dose Steroid Therapy

Objective--The efficacy of defibrinogenation therapy for idiopathic sudden sensorineural hearing loss was studied in comparison with high-dose steroid therapy.

Material and methods--Eighty-eight consecutive patients with hearing levels &gt;40 dB and who had suffered hearing loss for ≤30 days were enrolled: 40 patients for high-dose steroid therapy (PSL group) and 48 for defibrinogenation therapy (BX group). Hearing recovery was evaluated by grade assessment and by the improvement in hearing compared to the unaffected contralateral ear.

Results--The overall hearing outcomes of the two groups were roughly equivalent. However, with regard to patients with initial hearing levels &lt;80 dB, the hearing improvement rate of the BX group was significantly worse than that of the PSL group (61.2%±7.3% vs 88.7%±8.9%; p&lt;0.05), whereas in patients with initial hearing levels ≥80 dB, the hearing outcomes did not differ between the 2 groups. Three patients in the PSL group manifested hyperglycemia while no serious side-effects were observed in the BX group.

Conclusion--These results indicate that high-dose steroid therapy should be employed in preference to defibrinogenation therapy for patients with moderate hearing loss, whereas defibrinogenation therapy has an advantage for those with severe hearing loss, in view of its lower frequency of side-effects.     

小儿鼻窦炎的治疗

目的探讨小儿鼻窦炎的治疗方法,提高治疗效果,减少并发症。方法回顾性分析我院收治的100例小儿鼻窦炎,根据患儿不同情况采用药物鼻腔置换疗法、鼻内镜引导上颌窦自然开口置管冲洗及鼻内镜下功能性鼻窦手术治疗的疗效。结果痊愈74例,好转19例。总有效率为93%,全组病例无严重并发症。结论根据患儿不同情况采用药物鼻腔置换疗法、鼻内镜引导上颌窦自然开口置管冲洗及鼻内镜下功能性鼻窦手术治疗小儿鼻窦炎,治疗效果良好,值得临床推广。     

A Comparative Study of Azithromycin and Pseudoephedrine Hydrochloride for Otitis Media with Effusion in Children

We compared the outcomes of two different regimens azithromycin and pseudoephedrine hydrochloride (PHCl) for the treatment of otitis media with effusion (OME) in children. In a double-blind randomized clinical study, a total of 90 children aged between 2 and 13 years with persistent OME were randomly assigned to one of 3 treatment groups. The first group received azithromycin at a dose of 10 mg kg once daily for 3 days and this regimen was repeated weekly for up to 12 weeks according to the results of tympanometry and pneumatic otoscopy. The second group received azithromycin at a dose of 10 mg kg once daily for 3 days for the first week, and this regimen was repeated for 1 day a week for the following 11 weeks. The third group received PHCl, 4 mg kg, 3 times daily for up to 12 weeks. Each patient underwent pneumatic otoscopic and tympanometric investigations at baseline and at Weeks 4, 8 and 12. The outcomes in the azithromycin-treated groups were superior to that in the decongestant group. However, the difference between the outcomes in the azithromycin groups according to the treatment protocol was not statistically significant. Azithromycin therapy, particularly a once-weekly regimen, helps patients to comply with treatment and also helps us to achieve good results with minimal therapy.     

鼓室内灌注醋酸泼尼松龙治疗主观性耳鸣的临床观察

目的探讨鼓室内灌注激素时主观性耳鸣的治疗效果。方法选择病史在1月以上已接受过口服药物治疗的耳鸣患者49例(55耳),随机分为治疗组29例(30耳),鼓室内注入醋酸泼尼松龙,同时口服扩血管药及维生素;对照组20例(25耳),仅口服扩血管药及维生素,观察两组治疗前后耳鸣的变化。结果治疗组中,耳鸣伴突发性聋14耳、老年性聋3耳、噪声性聋2耳、耳硬化症1耳,原因尚不能明确的感音性聋5耳,混合性聋2耳及传导性聋1耳,特发性耳鸣2耳。经过一个疗程的治疗后,耳鸣消失5耳,减轻11耳,有效率53.3%(16/30)。对照组中,仅6耳耳鸣响度减轻,有效率24%(6/25)。结论鼓室内应用皮质类固醇激素能改善主观性耳鸣。     

颈动脉破裂引起致命性大出血的临床治疗分析

目的 探讨颈动脉破裂引起致命性出血的抢救方法。方法 回顾性分析本科2003年10月～2005年10月抢救的颈动脉破裂患者6例，总结经验教训。结果 6例患者中抢救成功4例，死亡2例。对于突发颈动脉壁破裂，应及时以大拇指压迫颈动脉，然后经皮肤用合适的缝针缝扎止血，综合治疗止血性休克，生命体征平稳后行血管介入治疗。结论 颈动脉破裂虽然出血汹涌，但只要抢救及时，方法妥当，是可以抢救成功的。     

鼻咽癌放疗后分泌性中耳炎的治疗

目的探讨治疗鼻咽癌放疗后分泌性中耳炎的治疗方法。方法将60例鼻咽癌放疗后并发分泌性中耳炎患者随机分为A、B两组,每组30例。A组鼓室置管;B组在鼻内镜下行鼻腔鼻咽部清理加鼓膜穿刺抽液加鼓室给药沐舒坦。比较分析两组治疗效果及并发症。结果随访10个月,60例中存活49例。存活患者中,分泌性中耳炎治疗有效率A组为52.6%,B组为81.6%,差异有统计学意义（P〈0.05）;并发症发生率A组为23.7%,B组为7.9%,差异有统计学意义（P〈0.05）。结论对鼻咽癌放疗后伴发的分泌性中耳炎治疗,鼻腔鼻咽部清理加鼓膜穿刺抽液加鼓室给药沐舒坦优于单纯鼓室置管引流。