The Infulence of Factors on Auditory and Speech Performances in Preschool Children with Unilateral Cochlear Implantation / 听力学及言语疾病杂志

Objective To investigate the affecting factors on auditory and speech performances in preschool children with unilateral cochlear implantation (CI) .Methods The clinical data of the preschool children (n=165) with unilateral cochlear implantation in the Second Xiangya hospital from January 2006 to April 2013 were collected . These children received rehabilitation according to the method recommended by the China Rehabilitation Research Center for Deaf Children ,and the data were analyzed retrospectively .The categories of auditory performance (CAP) and speech intelligibility rating (SIR) were used to assess their auditory and speech performances .The relationships between the performance and gender ,implanted age ,genotype ,inner ear malformation ,history of hearing aid were evaluated .Results Implanted ages and genotypes were associated with the auditory and speech performance of par‐ticipants (P<0 .05) ,while genders ,hearing aid experience ,and inner ear malformations(enlarged vestibular aque‐duct syndrome ,EVAS)were not significant related (P<0 .05) .Children were found to have achieved better CAP and SIR growths when CI was implanted during 1~3 years old and 2~4 years old ,respectively (P<0 .05) .The outcomes of CI recipients with GJB2 mutation were significantly better than those of the GJB2-nonrelated CI recipi‐ents (P<0 .05) .Conclusion This study provides evidence that CIs during first 1~3 years old having better auditory rehabilitation results than those of during 4~6 years old ,and CIs during 2~4 years old obtaining a better speech development in the first 12 months after operation .Deaf children with GJB2 mutation show better auditory and speech performances after CIs than those of the peers without GJB2 mutation .CIs can be effectively performed in deaf children associated with EVAs as in those without EVAS .

Treatment of esophageal perforation complicated with lethal massive hemorrhage induced by foreign body / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To explore the clinical characteristics and therapies for esophageal perforation complicated with lethal massive hemorrhage caused by esophageal foreign body.@*METHOD@#To retrospective analysis the treatment of massive hemorrhage at the carotid artery or aorta caused by esophageal foreign body in forty seven patients, Foreign body characters, surgical approaches, and postsurgical management were summarized.@*RESULT@#Among 24 patients with cervical esophageal foreign body, the object was removed either by esophagoscopy or through lateral cervical incision. After controlling carotid artery hemorrhage and repairing Fistula of artery from cervical incision, 19 patients survived. For the 23 patients with thoracic esophageal foreign body accompanied with aorta hemorrhea, thoracotomy was performed to remove the foreign body and repair the aortic fistula. Only 3 of these 23 patients recovered from the emergent surgery, other 20 patients died.@*CONCLUSION@#For the patients with esophageal foreign body inducing large vessel impingement, the most reliable therapeutic method is surgical repairing of arterial perforation and extraction of the foreign body via cervical or thoracic incision. Carotid ligation should be considered in patients with recurrent carotid hemorrhage. For the patient with mediastinitis, esophageal exclusion is recommended to prevent infection and to promote healing of aortic perforation after aortic fistula repairing.

Mutation screening in taperin gene in Chinese with prelingual nonsyndromic hearing impairment / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To screen and identify the frequency and characteristic of mutation in stereocilium-related gene Taperin of Chinese prelingual nonsyndromic hearing impairment with DNA microarray combined with PCR.@*METHOD@#One hundred and thirty-four patients of prelingual nonsyndromic deafness and one hundred health individuals in China were investigated in this study. Genomic DNA was extracted from the patients and was subjected to DNA microarray to screen mutations in 4 most common genes. The samples that carried none of the common mutant alleles were subjected to PCR and sequenced to detect mutations in Taperin gene.@*RESULT@#Ninteen out of one hundred and thirty-four patients of prelingual nonsyndromic deafness were detected carring common deafness gene with DNA microarray. Taperin gene were detected in one hundred and fifteen patients with PCR. A187S was detected in Taperin as hetrozygous state in 2 patients and their unaffected members of their family. It occurred at the evolutionary conservation of the amino acids of taperin according to alignment analysis. Two polymorphism, 157C>T and 318C>T, were found in the patients and the control group.@*CONCLUSION@#A novel Taperin mutation, A187S was detected in Chinese patients with prelingual nonsyndromic hearing loss, which may be relevant to hearing loss. Two polymorphism, 157C>T and 318C>T, were found in Chinese in our research. The carrier frequency for Taperin mutation is about 1.74% of prelingual nonsyndromic deafness in Chinese patients.

CD44 regulates epithelial-mesenchymal transition and metastasis in nasopharyngeal cancer cells / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To study the correlation of CD44 with epithelial-mesenchymal transition(EMT) and metastasis in nasopharyngeal cancer cells, and explore the possible mechanism of CD44 regulates EMT and metastasis in nasopharyngeal cancer cells.@*METHOD@#The CD44 and EMT-associated proteins in 5-8F and 6-10B nasopharyngeal cancer cell lines were assayed by Western blotting. The erasion trace test was performed to observe the migratory ability of 5-8F and 6-10B nasopharyngeal cancer cells. Using lipid-mediated DNA transfection technique, the low metastatic nasopharyngeal cancer cells 6-10B were transfected in vitro with plasmid which contained CD44 gene, and then new nasopharyngeal cancer cells were obtained. The CD44 and EMT-associated proteins in 6-10B, empty vector transfected and CD44-transfected cells were assayed by Western blotting. The erasion trace test was performed to observe the alteration of migratory ability of nasopharyngeal cancer cells before and after CD44 transfection.@*RESULT@#The expression of CD44 and EMT-associated protein MMP-9 in 5-8F was higher than that in 6-10B, but EMT-associated protein E-Cadherin in 5-8F was lower than that in 6-10B. The migratory ability of 5-8F was higher than that of 6-10B. The expression of CD44 and MMP-9 were significantly higher in the CD44-transfected nasopharyngeal cancer cells than in the control groups. Compared with control groups, the migratory ability of CD44-transfected nasopharyngeal cancer cells was significantly increased.@*CONCLUSION@#CD44 positively regulates the metastatic ability of nasopharyngeal cancer cells, which is relevant to the process of EMT.

Clinical analysis on extramedullary plasmacytoma in the upper airway / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the clinical manifestation, treatment and prognosis of extramedullary plasmacytoma(EMP) in the upper airway, and to improve the diagnosis and outcome of EMP treatment.@*METHOD@#Clinical data of 26 EMP cases were reviewed retrospectively, and then compared with multiple myeloma(MM) patients presenting with lesions in upper airway.@*RESULT@#Of 26 cases, 9 cases with the tumors occurred in nasal cavities, 7 in nasal sinuses, 6 in pharyngeal, 4 in throat, mainly manifesting with local masses and relevant symptoms. The manifestations of clinical, endoscopy findings and pathologic results in EMP patients were not distinguishable from the lesions of MM patients, while MM patients often accompanied by other findings, such as anemia and bone damage. Involvement of neck lymph nodes was more common in MM patients than in EMP patients. Ten patients were treated with surgery, and 16 patients with surgery and radiotherapy. Of the seven EMP patients with involvement of neck lymph nodes, four patients received additional chemotherapy besides surgery and radiotherapy, and no local relapse and MM happened in them, while of the three patients only received surgery and radiotherapy, one local relapse were found and one progressed to MM.@*CONCLUSION@#The diagnosis of EMPs mainly depends on pathological results. The judgment of pathologists and application of molecular biology technology are vital for the diagnosis of EMP in upper airway, and MM must be excluded very carefully in the diagnosis of EMP. Surgery combined with radiotherapy is the main treatment for EMP in the upper airway, and the prognosis is good but the follow-up should be taken. Besides surgery and radiotherapy, chemotherapy is beneficial for the EMP patients accompanied with lesions in neck lymph nodes.

Expression of TMPRSS3 in the rat cochlea following kanamycin ototoxicity / 中南大学学报(医学版)

OBJECTIVE@#To establish the kanamycin-induced deafness model in SD rats, and to investigate the expression and significance of transmembrane protease, serine 3 (TMPRSS3) in the cochlea following kanamycin ototoxicity.@*METHODS@#A total of 40 male SD rats were randomly divided into 4 groups. The experimental rats received intramuscular kanamycin sulfate for 3, 7, and 14 consecutive days, and the control group were treated with normal saline for 14 days. Auditory brainstem responses (ABR) were obtained before and after the kanamycin administration. The expression of TMPRSS3 in the cochlea was identified and detected by immunohistochemistry and Western blot.@*RESULTS@#Kanamycin-induced deafness model in the SD rats was successfully established. ABR thresholds were increased and the expression of TMPRSS3 in the cochlea was reduced after the kanamycin injection (P<0.01).@*CONCLUSION@#TMPRSS3 may play an important role in normal cochlea function and involve in the process of aminoglycoside antibiotics induced deafness.

Expression of proteinase TMPRSS3 in mouse cochlea / 中南大学学报(医学版)

OBJECTIVE@#To observe the expression of proteinase transmembrane protease, serine 3 (TMPRSS3) in mouse cochlea, and to investigate the significance of TMPRSS3 in the inner ear.@*METHODS@#The protein expression of TMPRSS3 in C57/BL mouse cochlea was identified and detected by immunohistochemistry and immunofluorescence. Different cochlear tissues, such as spiral ganglion neurons, corti organ, stria vascularis and so on, were separated to detect the gene expression of TMPRSS3 by real-time fluorescence quantitative polymerase chain reaction (qPCR). The cochlear tissues with different ages were collected and the expression of TMPRSS3 mRNA was detected by qPCR.@*RESULTS@#TMPRSS3 was mainly expressed in the spiral ganglion neurons, and there was TMPRSS3 mRNA in the cochlea in groups with different age. The expression level of TMPRSS3 mRNA was much weaker.@*CONCLUSION@#The distribution of TMPRSS3 was observed in many regions of the mouse cochlea, but mainly in the spiral ganglion neurons. This indicates that TMPRSS3 may be involved in the physiological functional regulation of the spiral ganglion neurons.

Expressions of LL-37 and IL-8 in chronic sinusitis with nasal polyps / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the expressions of LL-37 and IL-8 in chronic sinusitis with nasal polyps.@*METHOD@#Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical staining were used to detect the expressions of LL-37 and IL-8 in nasal polyp tissues of 31 patients with chronic sinusitis and inferior turbinate tissues of 11 patients with chronic rhinitis.@*RESULT@#LL-37 and IL-8 mRNA were all positively expressed in all nasal polyps and inferior turbinate tissues. There were significant increases of LL-37 and IL-8 mRNA expressions in nasal polyps compared with the inferior turbinate tissues (P < 0.01). There were also significant increases of positive expression rates of LL-37 and IL-8 protein in nasal polyps, compared with the inferior turbinate tissues (P < 0.01). There was a positive relationship between the mRNA and protein expressions of LL37 and IL-8 (P < 0.01).@*CONCLUSION@#The expressions of LL-37 and IL-8 in nasal polyps suggest that they may play a role in the pathogenesis of chronic sinusitis. Besides its innate immune, LL-37 could enhance human body's anti-infected function by increasing acquired immune.

Non-virus vector methods in hBDNF gene transfected bone marrow mesenchymal stem cells :Lipofectamine versus electroporation / 中国组织工程研究

BACKGROUND:Gene transfection of cells includes virus and non-virus vector.As virus vector has some issues,such as safety and immunological rejection,the present study explored lipofectamine and electroporation transfection methods.OBJECTIVE:To establish genetic engineering cells using human brain-derived neurotrophic factor(hBDNF)gene transfected bone marrow mesenchymal stem cells(BMMSCs)by lipofectamine or electroporation,and explore its characteristics and expression in vitro.METHODS:Lipofectamine method:The BMMSCs were obtained from the tibias and femurs of the guinea pigs.The third passage BMMSCs were cultured with plasmid-lipofectamine mixture for 6 hours,followed by fetal bovine medium for 48 hours.Immunohistochemistry was performed for transient expression.G418 was added after 48 hours.Electroporation method:BMMSCs were trypsinized and resuspended with serum-free medium.Cell suspension was added into electrotransformation pool,and plasmid was added.The electrotransformation pool was moved between electrodes.After transfection for 48 hours,gene transient expression was detected.G418 was added after 48 hours.Brain-derived neurotrophic factor expression was detected by immunohistochemistry and RT-PCR.RESULTS AND CONCLUSION:Immunohistochemistry showed that BDNF transient expression was 5.80% by lipofectamine and 24.29% by electroporation.Cells almost died at 14 days following lipofectamine transfection.Stable expression cell lines of BDNF engineered BMMSC were successfully established by electroporation,with 90% expressive rate by immunohistochemistry and expression of BDNF mRNA by RT-PCR.Genetic engineering cells using BDNF transected BMMSC were established by electroporation whereas failed by lipofectamine,and the expressed BDNF was confirmed by immunohistochemistry and RT-PCR in vitro.

The incidence of facial nerve dehiscence at mastoidectomy and its risk factors / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To study the incidence and locations of facial nerve dehiscence (FND) in mastoidectomy for the patients with cholesteatoma and chronic otitis media, and to determine its relevance as pre-operative prediction.@*METHOD@#Three hundred and fifteen ears (217 ears with cholesteatoma and 98 with chronic otitis media) undergoing mastoidectomy with or without tympanoplasties were selected for retrospective study, in which the incidence and locations of FND was studied, and the relevance for FND were analyzed by univariate test following by multivariate stepwise logistic regression.@*RESULT@#The presence of FND was 22.9% of total surgical procedures and the locations of FND were 93.1% in the tympanic segment, which was significantly higher than in the mastoid segment. The factors as otogenic facial paralysis, pathologic style (cholesteatoma or chronic otitis media) and lateral semicircular canal (LSC) fistula were related to FND, while others factors as sex, age, revision operations, preoperative complications, dural exposure, sigmoid sinus exposure were not risk factors for FND.@*CONCLUSION@#The incidence of FND was 22.9% in this study, the most common location for FND was in the tympanic segment, therefore, the facial nerves should be especially taken care in mastoidectomy for patients with presence of otogenic facial paralysis, cholesteatoma and LSC fistula.

A Preliminary Study on the Differentiation of bone-marrow mesenchymal Stem Cells into Neuron-like Cells in Vitro after transfected by Brain- derived neurotrophic Factor Gene / 听力学及言语疾病杂志

Objective To investigate the function of bone-marrow mesenehymal stem eells(BMSCs) differ-entiating into neuron-like cells in vitro after transfected by human brain-derived neurotrophie factor (BDNF) gene. Methods Human BDNF genes were cloned and recombinant pcDNA3. 1(-)-BDNF plasmids were construc-ted. BMSCs from five guinea pigs were isolated and cultured while their morphologies were observed by microscope. The surface antigen was detected by flowcytometry. BDNF genes were transfected into BMSCs with electroporation, and the transfected BMSCs were induced by ratinoie acid(RA)after bolted by Geneticin-418 (G418), then the dif-ferentiated BMSCs were identified by immunocytochemistry. Results The culture ceils demonstroted the typical mor-phology and surface antigen of BMSCs. The transfected cells expressed neuron- specific enolase(NSE), Nestin and glial fi-brillary acid protein(GFAP) also secreted BDNF. Conclusion BMSCs transfected by BDNF genes can differentiate into neu-ron- like cells in vitro, electroporation can enhame the transfection efficiency, RA can promote cell induction.

The expressions and clinical significance of tumor suppressor gene CX26 in laryngeal squamous cell carcinoma / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the expressions of tumor suppressor gene CX26 mRNA and coding protein in laryngeal squamous cell carcinoma, and to explore the relationship between CX26 gene and the biological behaviors of laryngeal squamous cell carcinoma for understanding the tumorigenicity and development of laryngeal squamous cell carcinoma.@*METHOD@#Laryngeal carcinoma tissues (studying group), which takeda from the center of tumors and laryngeal normal tissues (control group) takeda at the place of 1.0 cm out of the edge of the tumors, were took from 38 patients with laryngeal squamous cell carcinoma while they were in operation. Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) was used to analyze the expression level of CX26 mRNA, and immunohistochemical staining (frozen section) was used to detect the expression of CX26 protein in laryngeal carcinoma tissues and laryngeal normal tissues of 38 cases, respectively.@*RESULT@#mRNA of CX26 gene was all positively expressed in laryngeal carcinoma tissues and laryngeal normal tissues of 38 cases by RT-PCR. However, CX26 mRNA was obviously down-regulated in laryngeal carcinoma tissues than that in laryngeal normal tissues (P < 0.05). Immunohistochemical staining showed CX26 protein was strong-positively expressed in laryngeal normal tissues in 34 cases (89.5%), while it was positively expressed in laryngeal carcinoma tissues in 18 cases (47.4%), and with the location alteration of CX26 protein in laryngeal carcinoma cells. There was significant difference between the expression rate of CX26 protein in laryngeal carcinoma tissues and in laryngeal normal tissues (P < 0.05). Meanwhile, the expression level of CX26 mRNA and the positive-expressed rate of CX26 protein of the laryngeal carcinoma tissues in the advanced stage patients group (III stage and IV stage) were significantly lower than these in the early stage patients group (I and II) (P < 0.05), and it was significantly lower in those who have a cervical lymph node metastasis than those without metastasis. (P < 0.05). Moreover, the expression level of CX26 mRNA and the positive-expressed rate of CX26 protein reduced along with the reduction of pathological differentiation, and there was significant difference among the well-differentiated group, moderately-differentiated group and poorly-differentiated group (P < 0.05).@*CONCLUSION@#CX26 gene may play an important role in the pathogenesis and development of laryngeal carcinoma and may be related to its prognosis.

Differentially expressed proteins of the fibroblast cell-secreted protein in nasopharyngeal carcinoma / 中华检验医学杂志

Objectives To establish the two-dimensional electrophoresis(2-DE)profile of cell. Secreted proteins.Difierential expression profiling of fibroblast cell secreted proteins between nasopharyngeal carcinoma and normal nasopharyngeal tissue was analyzed.Methods Five tissue specimens each from patients with nasopharyngeal carcinoma and nasal polyp were collected individually.Fibroblast eells from above-mentioned tissue were cultured in serum-free medium,and cell-secreted proteins from the cultured medium were harvested by uhrafihration concentration and desalination.Samples were analyzed by 2-DE,and the differentially expressed proteins were analyzed and identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry.Galectin-1 wa8 analyzed by EUSA test.Results 2-DE diagram of fibroblast cell-secreted proteins Was constructed.1 8 protein spots displayed quantitative changes in expression,and 11 protein spots among them were identified by mass speetrometrv.3 proteins including cystatin C,complement subcomponent C1S precursor,heterogeneous nuclear ribonueleoprotein A1 were down-regulated in the cultured medium of nasopharyngeal carcinoma associated fibroblast cells(CAFs). Nevertheless,the rest cell-secreted proteins including galectin-1,14-3-3 protein sigma,eathepsin L and etc,were up-regulated.Meanwhile,the expression of galectin-1 in the cultured medium was also analyzed and Its results were compared between CAFs and the normal fibroblast cells by ELISA.There Was statistical significance difference between them,and galectin-1 was up-regulated in the cIlltured medium of CAFs.Conclusions The changes of fibroblast cell-secreted proteins during nasopharyngeal carcinogenesi8 are analyzed by 2-DE analysis.The variation of pattern of secreted proteins is involved in signal transduction,protein synthesis,degradation and other pathways.CAFs may regulate tumor microenvironment by the abeve-mentioned pathways,and influence nasopharyngeal carcinogenesis,progress,invasion and metastasis.This study provided experimental basis for the eell secreted proteomics studv in future.

Clinical analysis of extramedullary plasmacytomas in the head and neck / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To summarize the clinical features and the experiences of diagnosis and treatment of extramedullary plasmacytomas (EMPs), and to enhance the cure rates of EMPs.@*METHOD@#Clinical data of 8 patients with EMPs in head and neck, who treated in our hospital from Jan. 1990 to Dec. 2004, were reviewed. Of 8 cases, 3 cases with the tumors occurred in nasal cavities, 1 in maxillary sinus, 2 in nasopharynx, 1 in posterior wall of oropharynx.@*RESULT@#Eight patients who were all pathologic confirmed EMP accepted surgical resections of the tumors, and 4 of 8 cases were boosted radiation therapy post-operation. Four cases were still alive disease-free for more than 1, 5, 10 and 12 years after treatments, respectively. One died of local recurrence in 2 years, 1 died of multiple myeloma in 3 year, and 1 died of heart attack in 2 years after treatments, respectively. One lost follow-up.@*CONCLUSION@#EMPs in head and neck are low potential malignancy tumors. The diagnosis of EMPs mainly depends on clinical manifestations and pathological results. Surgery and radiation therapy are the main treatments for EMPs in head and neck.

Diagnosis and surgical treatment of the carotid body tumors / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To enhance the cure rate and lower the complication rate and the mortality rate through summarizing the clinical features and experiences in diagnosis and therapy of carotid body tumor (CBT).@*METHOD@#Retrospectively analyzed the clinical data of 21 cases (23 sides) of CBT from 1995-2095 occurring in our hospital.@*RESULT@#The accurate diagnosis rates hy using digital subtraction angiography (DSA) and magnetic resonance imaging (MRI) were 100%. Seventeen cases (19 sides) accepted surgical operation with different kinds of procedures. The tumors of 8 cases were simplex isolated from the carotid artery. Both the tumour and the external carotid artery were resected in 9 cases. One case underwent resection of both the internal and external carotid artery and the tumour without carotid reconstruction. One case underwent resection of the internal, external carotid artery and the tumor with reconstruction of the internal carotid artery. No operative mortality was observed. The ventricular arrhythmia which had not been controlled pre-operation occurred in 1 case who was finally self-cured. One case had hoarseness and completely recovered in one week. and 1 case without carotid reconstruction had a frequent headache and gradually recovered in 5 months. The others had no complications.@*CONCLUSION@#OSA and MRI are the best methods for diagnosing CBT. Surgery is the first choice concerning the treatment of CBT. Accurate preoperative evaluation, correct therapeutic decision exquisite vascular surgical techniques can help to significantly decrease, even avoid the complications.

Diagnosis and management of lipogranuloma of the eyelids from nasal endoscopic surgery / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To enhance the safety of nasal endoscopic surgery and decrease its complications of eyes.@*METHOD@#Three patients of chronic rhinosinusitis and nasal polyposis with lipogranulomas of the eyelids after nasal endoscopic surgery and nasal packing of petrolatum gauze were reported and analyzed, and their treatment results were presented during the last 2 years.@*RESULT@#The medial orbital wall injury occurred in all three patients during endoscopic sinus surgery. The patients developed an ipsilateral periocular swelling, eyelid hematoma and palpebral conjunctival edema during 2 to 3 hours after surgery. Nasal packs petrolatum gauze were removed 10-24 hours after surgery. The patients were discharged from hospital when periorbital swelling and eyelid ecchymoma disappeared, and nasal cavity obstruction was improved 6 to 8 days after surgery. The swelling and nodular mass of ipsilateral eyelids (one in left upper eyelid and two in right lower eyelid) were found 12-15 days after surgery, and their eye movement and eyesight were normal. Antibiotic and corticosteroid were administered for 3 4 weeks with only improvement in eyelid swelling. These masses of eyelids were completely excised through palpebral margin 1-6 months after surgery. The histopathological examination of the surgical specimens showed lipogranuloma. No recurrence and symptom of the eyes had been observed during 4-18 months follow up.@*CONCLUSION@#The lipogranuloma of the eyelid is a rare and late complication after nasal endoscopic surgery and nasal packing with vaspetrolatum gauze. The medial orbital wall injury and bleeding during surgery, and vaseline of nasal packing permeated into the eyelid are the direct causes of this complication. The application of petrolatum gauze should be avoided when the medial orbital wall trauma is identified. The complete excision of granulomas is a best effective therapy.

A Member of Ⅱ Transmembrane Serine,TMPRSS3 and Hereditary Deafness / 生物化学与生物物理进展

TMPRSS3 (transmembrane protease, serine 3) is a member of Ⅱ transmembrane serine proteases (TTSPs), and like the other members of this family, it contains typical domains including a serine protease domain, a transmembrane domain, a LDL receptor-like domain (LDLRA), and a scavenger receptor cysteine-rich domain (SRCR). Four alternative protein isoforms have been described, and isoform A is thought to be primary isoform which is expressed in many tissues, especially in the cochlea. TMPRSS3 protein is primarily localized in the endoplasmic reticulum membranes where it may be anchored by its transmembrane domain. TMPRSS3 is mutated in non-syndromic autosomal recessive deafness (DFNB8/10). Therefore TMPRSS3 is thought to be involved in the development and maintenance of the inner ear, and isoform D may be proposed as a novel diagnostic marker in ovarian carcinoma. TMPRSS3 protein is the first protease which mutation could lead to deafness. These data indicate that important signaling pathways in the inner ear are controlled by proteolytic cleavage. However, it is not clear about TMPRSS3 substrates and its function. The epithelial amiloride-sensitive sodium channel (ENaC) which is regulated by membrane-bound channel activating serine proteases (CAPs), a member of TTSPs, may be a potential substrate of TMPRSS3, but this hypothesis is still to be verified in vivo. With the development of protease research and the application of protease proteomics, substrate degradomes of a protease may therefore represent an important tool for the research of TMPRSS3 function and its molecular mechanism.

Deafness genes for nonsyndromic hearing loss and current studies in China / 中华医学杂志(英文版)

<p><b>OBJECTIVES</b>To review the identified deafness genes related to nonsyndromic hearing loss (NSHL) and summarize their expressions and functions in the cochlea and to introduce the current studies of molecular genetics on NSHL in China.</p><p><b>METHODS</b>The presented data are based on a review of the literature as well as the author' s experience with NSHL and communications with other researchers in China over the past 3 years.</p><p><b>RESULTS</b>Currently, 23 deafness genes related to NSHL have been cloned and identified. Some genes are associated with both NSHL and syndromic hearing loss (SHL), in both dominant and recessive deafness. Deafness genes have a highly specific expression pattern in the inner ear. Some functional categories are starting to emerge from a characterization of deafness genes. There are interacting genes in the genetic background that influence the extent of hearing impairment. The GJB3 gene, which is associated with high-frequency hearing impairment, was cloned in a Chinese laboratory. Mutations in some genes, such as GJB2 and mitochondrial 12S rRNA, have been screened in Chinese patients with NSHL. Mapping new deafness gene loci as well as identifying new genes and their functions is an active area of study in China.</p><p><b>CONCLUSIONS</b>It is challenging for us to continue identifying new deafness genes and analyze gene functions. By identifying genes responsible for monogenic hearing impairment, more insight may be gained into the molecular process of hearing and the pathology of hearing loss.</p>

Morphological and Functional Alterations of Ear in Lysosomal Protective Protein/Cathepsin A Gene Knock Out Mouse / 听力学及言语疾病杂志

Objective Galactosialidosis(GS) is an autosomal recessive lysosomal storage disease caused by a combined deficiency of lysosomal ?-galactosidase and neuraminidase as a result of a primary defect in the protective protein/cathepsin A(PPCA).Mouse model of GS has been generated by targeted deletion of PPCA gene and closely resembled the phenotypes in human conditions.However,it remains to be determined whether hearing loss observed in human also occurs in the mouse model.In this study,we observed their alterations of the auditory function and morphology of the ear,and explored pathophysiological mechanisms of hearing impairment.Methods PPCA homozygous(PPCA-/-) mice at 1 and 2 months of age,and their wildtype littermates(PPCA+/+) were examined for auditory thresholds through auditory brainstem responses(ABR) to click,tone pips 8,16,and 32 kHz stimuli.Morphological analyses in ears were performed by series temporal bone section and light microscopy.Results PPCA-/-mice at 1 month of age showed a normal threshold and the morphology of ears.Up to 2months of age,their thresholds were elevated 40～45 dB SPL above those of PPCA+/+ mice.There were distinct pathological changes of middle and inner ear in PPCA-/-mice of 2 months old.The severe otitis media and the vacuolation associated with lysosomal storage were observed within ossicles and cochlear bone cells,stria vascularis cells,spiral ganglion neurons,spiral limbus,Reissner's membrane cells,and the mesothelial cells of the perilymphatic scala and basilar membrane,but not within the organ of Corti.Vestibular organ did not show vacuolation.Conclusion The deficiency of lysosomal protective protein/cathepsin A may result in hearing loss and morphological alterations of ear.The otitis media and ossicle changes,and the defects in lysosomal storage of neurons,stria vascularis,spiral limbus,Reissner's membrane and basilar membrane cells may contribute to the conductive and sensorineural hearing loss respectively.

Protective Role of BDNF and NGF Against Cisplatin-Induced Ototoxicity / 听力学及言语疾病杂志

Objective To study the expression of brain-derived neurotrophic factor(BDNF) and nerve growth factor(NGF) in the guinea pig cochlea of cisplatin-induced ototoxicity, and to understand its protective role for the inner ear.Methods The animals were divided into normal group and experimental group with cisplatin. Sodium chloride was used for the control. All animals were sacrificed on the day 3, 5 and 7, and the cochlea were used for BDNF and NGF staining.Results The weak expression of BDNF and the moderate expression of NGF were observed in the cochlea in the normal group. The strongest expression of BDNF and NGF was observed in the animals with cisplatin.Conclusion The existence of NGF in the normal cochlea indicates that NGF plays an important role to maintain auditory physiology.BDNF and NGF may be involved in self-protection mechanism for the cochlea and auditory nerves from cisplatin-induced ototoxicity.