Exosomes derived from cochlear spiral ganglion progenitor cells prevent cochlea damage from ischemia-reperfusion injury via inhibiting the inflammatory process.

Ischemia-reperfusion injury (I/R)-induced inflammatory process can mediate cochlea damage-related hearing loss; whether cochlear spiral ganglion progenitor cell-derived exosomes (CSGPC-exos) play a protective role by carrying functional microRNAs into recipient cells is unknown. Different doses of CSGPC-exos (0.1 µg/µl, 0.2 µg/µl, 0.5 µg/µl, 1.0 µg/µl) were administrated into the cochleae of the I/R group induced with 30-min occlusion of the bilateral vertebral arteries and sham surgery group. The speech-evoked auditory brainstem response (ABR) test was utilized to estimate the auditory threshold shift. The relative expression of proinflammatory cytokines was detected with RT-PCR and Western blot, while parvalbumin and caspase-3 expression were detected by immunofluorescence staining in the cochleae. The relative expression of microRNAs (miR-21-5p, miR-26a-5p, and miR-181a-5p) was detected in the cochleae. I/R significantly up-regulated ABR threshold shift and promoted hair cell apoptosis indicated by parvalbumin and caspase-3 staining, while CSGPC-exos (0.5 µg/µl, 1.0 µg/µl) could diminish such damages with downregulated proinflammatory factors (IL-6, IL-1ß, TNF-α, and Cox-2) and upregulated anti-inflammatory miRNAs (miR-21-5p, miR-26a-5p, and miR-181a-5p) expression in the cochleae. CSGPC-exos could protect cochleae damage from I/R, probably via inhibiting the inflammatory process.

Value of CT and three-dimensional reconstruction revealing specific radiological signs for screening causative high jugular bulb in patients with Meniere's disease.

BACKGROUND: The aim of the present study was to investigate the pathological features of vestibular aqueduct (VA) related high jugular bulb (HJB) and explore the possible cause-consequence relation between HJB and endolymphatic hydrops (EH), and the potential specific radiological signs for screening causative HJB in Meniere's disease (MD). METHODS: High-resolution computed tomography (HRCT) and three-dimensional reconstruction (3DRC) were used to detect the anatomical variables associated with VA and jugular bulb (JB) in hydropic and non-hydropic ears. The presence or absence of EH in the inner ear was determined by gadopentetate dimeglumine-enhanced magnetic resonance imaging. The presence of different types of HJB, the anatomical variables of the VA and JB and the three types of anatomical relationship between the VA and HJB were compared between the hydropic and non-hydropic ears using the χ2 or Fisher's exact tests. P < 0.05 was considered to indicate a statistically significant difference. RESULTS: JB was classified as: Type 1, no bulb; type 2, below the inferior margin of the posterior semicircular canal (PSCC); type 3, between the inferior margin of the PSCC and the inferior margin of the internal auditory canal (IAC); type 4, above the inferior margin of the IAC. There were no significant differences in the presence of types 1, 2 and 3 JB between two groups. The presence of type 4 JB, average height of the JB and prevalence of the non-visualization of the VA in CT scans showed significant differences between two groups. The morphological pattern between the JB and VA revealing by 3DRC was classified as: Type I, the JB was not in contact with the VA; type II, the JB was in contact with the VA, but the latter was intact without obstruction; type III, the VA was obliterated by HJB encroachment. There were no significant differences in the presence of type I and II between two groups. Type III was identified in 5 hydropic ears but no non-hydropic ears, with a significant difference observed between the two groups. CONCLUSION: The present results showed that JB height and non-visualization of the VA on Pöschl's plane could render patients susceptible to the development of EH. A jugular bulb reaching above the inferior margin of the IAC (type 4 JB) could obstruct VA, resulting in EH in a few isolated patients with MD. VA obliteration revealed by 3DRC, as a specific radiological sign, may have the potential for screening causative HJB in MD.

Assessment of hearing loss induced by tympanic membrane perforations under blast environment.

PURPOSES: This study provides an approach to estimating tympanic membrane perforation-induced hearing loss (HL) using a human middle ear model. METHODS: Sixty-one cases of tympanic membrane perforation originating from fireworks were reported from the Ear-Nose-Throat Department. The otoscope, audiometry data and diagnosis records were organized, and gender, age, etiology, perforation size and diseased ear side were classified as independent variables. A multinomial regression model was used to analyze the potential effects of the variables on HL. Meanwhile, a human middle ear model was implemented to calculate the ensued HL resulting from different perforation areas and sites. In addition, linear regression models were used to establish functions between perforation size and HL. RESULTS: The audiometry data indicate that HL at high frequencies (f > 2 kHz) is much more profound than that at the speech frequency band (f < 1 kHz). Compared with mild HL (<15 dB), mediate HL (15-30 dB) was correlated with the perforation area (p < 0.05, 95% CI), while severe HL (>30 dB) was affected by both perforation size and age (p < 0.05, 95% CI). However, other factors, including gender and diseased ear side, do not show a statistically significant effect on HL. Furthermore, the Kruskal-Wallis test result reveals that HL at frequencies of 0.25 kHz ≤ f ≤ 8 kHz is strongly associated with the perforation size (p < 0.05, 95% CI). CONCLUSIONS: It is conclusive that HL is positively proportional to the perforation size. However, HL is not correlated with the perforation site for small perforation areas of < 10% (p > 0.05, 95% CI).

TMPRSS3 regulates cell viability and apoptosis processes of HEI-OC1 cells via regulation of the circ-Slc4a2, miR-182 and Akt cascade.

BACKGROUND: The present study aimed to investigate the functions and regulation mechanism of the transmembrane protease, serine 3 (TMPRSS3), which plays an important role in sensorineural hearing loss. METHODS: House Ear Institute-Organ of Corti 1 (HEI-OC1) cells, comprising auditory-related cells, were used in the present study. An overexpression vector and small hairpin RNA target on TMPRSS3 were designed and transfected into HEI-OC1 cells. Circular RNA (circRNA) sequencing was conducted and expression profiles were obtained. The circular structure of circRNAs was validated with a polymerase chain reaction and Sanger sequencing using convergent and divergent primers. RESULTS: Overexpression of TMPRSS3 increased cell viability, whereas suppression of TMPRSS3 increased the percentage of apoptotic cells and decreased cell viability, compared to the control group. circRNA sequencing provided expression profiles indicating that the overexpression of TMPRSS3 increased the expression level of 195 circRNAs. Results of GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) studies indicated that the circRNAs are focused on the RAS signaling pathway. The pathway, circ-Slc41a2 (chr10: 82744115|82767120), miR-182 and Akt, might comprise one of the key cascades of TMPRSS3. CONCLUSIONS: TMPRSS3 is an important molecule in the regulation of cell viability and cell apoptosis of HEI-OC1 cells. Its functions are dependent on the circ-Slc41a2, miR-182 and Akt cascade.

Microarray Analysis of Differentially-expressed MicroRNAs in Acquired Middle Ear Cholesteatoma.

Objectives: To analyze the miRNAs expression profiling between acquired middle ear cholesteatoma and normal skin, and to identify several novel miRNAs which may be involved in the etiopathogenesis of middle ear cholesteatoma. Methods: MiRNA microarray technology was adopted to analyze the miRNA expression profiling between acquired middle ear cholesteatoma and normal skin. qRT-PCR was used to validate selected differentially expressed miRNAs. Results: The miRNA microarray technology showed totally 44 upregulated (miRNA-21-3p, miRNA-584-5p, miRNA-16-1-3p, etc) and 175 downregulated (miRNA-10a-5p, miRNA-152-5p, miRNA-203b-5p, etc) miRNAs in cholesteatoma tissues with 2-fold change compared with normal skin. The qRT-PCR validation was in accordance with the microarray results partly: miRNA-21-3p and miRNA-16-1-3p expressed significantly higher while miRNA-10a-5p exhibited an obviously decreased expression in middle ear cholesteatoma tissues when compared with normal skin. The GO and KEGG pathway analyses provided clues that these differentially expressed miRNAs might play essential roles in the etiopathogenesis of middle ear cholesteatoma, including cell proliferation, apoptosis, cell cycle, differentiation, bone resorption and remodeling process. Conclusions: Our study suggests possible roles of differentially expressed miRNAs in the pathogenesis of middle ear cholesteatoma. Targeting on these miRNAs may provide a new strategy for cholesteatoma therapy in the future.

Anti-neutrophil cytoplasmic antibody-associated hypertrophic cranial pachymeningitis and otitis media: a review of literature.

BACKGROUND AND OBJECTIVE: It has been recognized that anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides may lead to hypertrophic pachymeningitis (HP) or intractable otitis media (OM). To our knowledge, few cases of coexistent ANCA-related HP and OM have been described previously. To increase awareness of this disease, we reviewed the literature describing patients with HP and intractable OM in a population with AAV to guide clinical decision making for otolaryngologists. METHODS:  PubMed was searched with the following terms: ANCA-associated vasculitis, otitis media, and hypertrophic pachymeningitis. Only patients with concomitant AAV, OM and HP were considered and included in this review. RESULTS: A total of 243 articles were reviewed, and of these, 6 met inclusion criteria. Headache, cranial polyneuropathy, and intractable OM with effusion or granulation were common. Serum MPO-ANCA positivity was most common in Asian patients. Almost all patients had dural mater thickening on gadolinium-enhanced magnetic resonance imaging of the brain. Corticosteroids plus an immunosuppressant was more effective and most patients had improved hearing after treatment, but approximately 50% of subjects had disease relapse. CONCLUSION: In this review, we summarized the current knowledge on the clinical features, diagnosis, treatment, and pathogenesis of this disease. We should carefully detect the potential cases of ANCA-related HP and OM in patients with intractable OM, HP, or AAV, and make the optimal treatment plan to avoid long-term neurological complications and irreversible hearing loss. Furthermore, due to an increased possibility of relapse, close follow-up, including a hearing test, ANCA titers, imaging examination, and detection of toxic and side effects of immunosuppressive therapy, are necessary.

A review of the management and prognosis of thyroid carcinoma with tracheal invasion.

The objective of the study was to explore the surgical approaches, treatment significance and prognosis of thyroid carcinoma with tracheal invasion. We retrospectively reviewed 48 patients with tracheal invasion by papillary thyroid carcinoma, follicular thyroid carcinoma and medullary thyroid carcinoma by means of clinical data ranging from 1993 to 2011. The patients were classified into three groups in terms of the depth and extent of tracheal invasion by the tumors, i.e., group A of 18 patients with localized tracheal invasion; group B of 21 patients with intraluminal tracheal invasion, and group C of nine patients with extensive invasion of the trachea, larynx, esophagus and/or mediastinum. Of these patients, 18 received radical tumorectomy and segmental resection of the outer layer of the tracheal wall; 21 had radical tumorectomy, circumferential sleeve trachea resection or segmental tracheal resection plus tracheal repair, and the remaining nine patients underwent radical tumorectomy, segmental trachea resection and esophagolaryngectomy. 46 patients took I(131) oral solution and/or had external radiotherapy postoperatively. A survival analysis was done using Kaplan-Meier Estimator for cumulative survival probability together with Log-Rank test, and Cox Regression Model was used for multivariate analysis. (1) In group A of 18 patients, 10 took I(131)oral solution and 7 received radiotherapy after surgery. The overall 5 and 10-year survival rates were 88.93 and 77.78 %, respectively; (2) In group B of 21 patients, 15 took I(131) oral solution and 7 received radiotherapy after surgery. The overall 5 and 10-year survival rates were 90.47 and 61.87 %, respectively; (3) In group C of 9 patients, 7 received radiotherapy after surgery. The overall 5 and 10-year survival rates were 77.78 and 22.22 %, respectively. Whether they received postsurgical I(131) treatment or radiotherapy, there was a statistical difference between the 5-year survival rates and the 10-year survival rates in all of these three groups (P value in each group is <0.05). In the treatment of thyroid carcinoma with tracheal invasion, radical tumorectomy plus tracheal repair, segmental tracheal resection or circumferential sleeve trachea resection could lengthen the survival time. Radical tumorectomy could enhance the probability of survival of patients with thyroid carcinoma that had extensively invaded the larynx, esophagus and/or mediastinum. Postsurgical I(131) treatment and radiotherapy enhanced the probability of survival.

Clinical manifestation and management of primary malignant tumors of the cervical trachea.

To explore clinical manifestation and therapies of primary malignant tumors of the cervical trachea, we retrospectively reviewed 31 patients with primary cervical tracheal malignant tumors diagnosed in the last 15 years by means of clinical manifestation, fiberoptic endoscopy, CT scanning and histopathological examinations. All of them were hospitalized and treated at the Second Xiangya Hospital, Central South University. Of them, 4 underwent emergent tracheotomy under local anesthesia, 9 were inserted with a laryngeal mask airway, 18 underwent tumorectomy under general anesthesia with endotracheal intubation, and of them 11 had tracheotomy during surgery. Of those 31 patients, tracheal malignant tumors in 9 cases were resected via laryngeal and retrograde tracheal incisions under endoscope; the tumors in 13 cases were excised via sleeve trachea resection and end-to-end anastomosis; those in 8 were removed by tracheofissure, and the tumor in 1 case was not excised surgically. Among the 30 resected patients, 20 patients received both radiotherapy and chemotherapy; 6 received radiotherapy only, and 4 did not receive any adjuvant therapies. During follow-up between 2 and 11 years, among 31 patients, there was no recurrence in 24 cases. Among the 7 deceased patients, 1 displayed multiple tracheal chondrosarcoma, 4 displayed adenoid cystic carcinoma, and 2 displayed squamous cell carcinoma. Emergency lower tracheotomy is necessary only when patients with tracheal, malignant tumors are in a critical condition. Sleeve trachea resection is the optimal therapy for tracheal malignant tumors. However, in the treatment of tracheal malignant tumors adjacent to the larynx or the involved trachea is over 6 cm in length, other surgeries shall be performed. Postoperative adjuvant radiotherapy and chemotherapy can achieve the same therapeutic effect as sleeve trachea resection.

Untargeted Metabolomic Analysis in Endolymphatic Sac Luminal Fluid from Patients with Meniere's Disease.

Dysfunction of the endolymphatic sac (ES) is one of the etiologies of Meniere's disease (MD), the mechanism of which remains unclear. The aim of the present study was to explore the molecular pathological characteristics of ES during the development of MD. Metabolomic profiling of ES luminal fluid from patients with MD and patients with acoustic neuroma (AN) was performed. Diluted ES luminal fluid (ELF) samples were obtained from 10 patients who underwent endolymphatic duct blockage for the treatment of intractable MD and from 6 patients who underwent translabyrinthine surgery for AN. ELF analysis was performed using liquid chromatography-mass spectrometry before the raw data were normalized and subjected to subsequent statistical analysis by MetaboAnalyst. Using thresholds of P ≤ 0.05 and variable important in projection > 1, a total of 111 differential metabolites were screened in the ELF, including 52 metabolites in negative mode and 59 in positive mode. Furthermore, 15 differentially altered metabolites corresponding to 15 compound names were identified using a Student's t-test, including 7 significant increased metabolites and 8 significant decreased metabolites. Moreover, two differentially altered metabolites, hyaluronic acid (HA) and 4-hydroxynonenal (4-HNE), were validated to be upregulated in the epithelial lining of the ES, as well as in the subepithelial connective-tissue in patients with MD comparing with that in patients with AN. Among these differentially altered metabolites, an upregulated expression of HA detected in the ES lumen of the patients with MD was supposed to be associated with the increased endolymph in ES, while an increased level of 4-HNE found in the ELF of the patients with MD provided direct evidence to support that oxidative damage and inflammatory lesions underlie the mechanism of MD. Furthermore, citrate and ethylenediaminetetraacetic acid were detected to be decreased substantially in the ELF of the patients with MD, suggesting the elevated endolymphatic Ca2+ in the ears with chronic endolymphatic hydrops is likely to be associated with the reduction of these two chelators of Ca2+ in ES. The results in the present study indicate metabolomic analysis in the ELF of the patients with MD can potentially improve our understanding on the molecular pathophysiological mechanism in the ES during the development of MD.

Meniere's Disease Patients with Distinct Sac Pathoanatomic Findings React Differently to Endolymphatic Duct Blockage.

OBJECTIVES: To explore the possible difference in response to endolymphatic duct blockage (EDB) treatment in patients with Meniere's disease (MD) with distinct pathoanatomic characteristics of the sac. METHODS: In a total of 24 patients with MD receiving EDB treatment, the dynamics of the vertigo attack, hearing, vestibular function, and endolymph hydrops (EH) before surgery and 40 months following surgery in patients with normoplastic extraosseous portion of endolymphatic sac (eES) were compared with that in patients with atrophic eES. RESULTS: A higher prevalence of complete vertigo control, better cochlear and vestibular function, and lower endolymph to vestibule-volume ratio were found in patients with normoplastic eES than in those with atrophic eES. Moreover, the reversal of EH was found in a total of six patients in normoplastic eES group, but no reversal of EH was detected in the atrophic eES group after surgery. CONCLUSIONS: A difference in response to EDB treatment was shown in the MD patients with normoplastic eES and those with atrophic eES; the reversal of EH was found in the normoplastic eES group, but not in the atrophic eES group after surgery, suggesting two distinct pathologies in the eESs may underlie the pathogenesis of EH in two subgroups of MD patients. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2761-2769, 2023.

Study of clinical treatment of esophageal foreign body-induced esophageal perforation with lethal complications.

Esophageal foreign body-induced esophageal perforation is a lethal complication and its treatment very complex. We had reviewed 1,428 patients with esophageal foreign body, who were hospitalized and treated over the past 25 years. A classification summary was made of 121 patients (of these 1,428 cases) who presented with esophageal foreign body-induced perforation and complicated cervical abscess, mediastinitis, and mediastinal abscess. This summary considered foreign body types, location and lodging duration, complications, and surgical approaches. Among these 121 patients, esophageal foreign bodies in 81 patients were successfully extracted via esophagoscope or fiber optic esophagoscope. Cervical esophageal foreign bodies in 22 patients were extracted by esophagoscope and lateral cervical incision (n = 6) and simple lateral cervical incision (n = 16). Thoracotomy was performed to remove thoracic esophageal foreign bodies in 18 patients with 10 successes and 8 failures. Of the 121 patients, 67 patients with cervical abscess were cured by means of lateral cervical abscess incision and drainage, esophageal stent placement, and esophageal perforation repair with pedicle myolemma or pedicle muscular periosteum flap. 54 patients with mediastinitis and/or abscess were all cured, except one mortality, by means of mediastinotomy and drainage or/and closed-chest drainage, simple esophageal repair, esophageal repair with pedicle myolemma or pedicle muscular periosteum flap and stent placement for esophageal perforation, and esophageal exclusion plus two-stage gastric-pharyngeal anastomosis. In the treatment of esophageal foreign body-induced severe complications, various therapies should be applied simultaneously. Lateral cervical incision should be made immediately to remove the foreign bodies if the foreign body extraction under esophagoscope proves to be a failure after repeated attempts, or esophageal perforation develops during the procedure, or should cervical abscess develop. Mediastinotomy and drainage or/and closed-chest drainage should be carried out as early as possible when mediastinitis and/or mediastinal abscess develops after esophageal foreign body ingestion.

Exosomes derived from heat shock preconditioned bone marrow mesenchymal stem cells alleviate cisplatin-induced ototoxicity in mice.

NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome contributes to the development of cisplatin-induced ototoxicity. Whether heat shock pretreatment could be utilized to up-regulate 70 kilodalton heat shock proteins (HSP70) expression in bone marrow mesenchymal stem cells (BMSCs)-derived exosomes (HS-BMSC-Exo) to alleviate cisplatin-induced ototoxicity is deciphered in this study. Heat shock pretreatment was performed on BMSCs to induce HS-BMSC-Exo, which were further trans-tympanically administrated into cisplatin intraperitoneally injected C57BL/6 mice. Auditory brainstem response (ABR) was assessed to indicate auditory sensitivity at 8, 16, 24, and 32 kHz. Myosin 7a staining was utilized to detect the mature hair cells. The relative expressions of the NLRP3 inflammasome complex were determined with Western blot in the cochlea. Diminished auditory sensitivity and increased hair cell loss could be observed in the cisplatin exposed mice with increased content of interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, NLRP3, ASC, cleaved caspase-1, and pro-caspase-1, and decreased content of IL-10, which could be reversed by HS-BMSC-Exo or BMSC-Exo administration. It was worth noting that HS-BMSC-Exo demonstrated more treatment benefits than BMSC-Exo in cisplatin-induced ototoxicity. Heat shock precondition may provide a new therapeutic option to produce exosomal HSP70, and HS-BMSC-Exo could be utilized to relieve cisplatin-induced ototoxicity.

Exosomes Derived from Bone Marrow-Mesenchymal Stem Cells Attenuates Cisplatin-Induced Ototoxicity in a Mouse Model.

BACKGROUND: Both hypoxia preconditioning and exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exo) have been adopted to alleviate hair-loss-related ototoxicity. Whether hypoxic BMSCs-derived exosomes (hypBMSC-Exo) could alleviate cisplatin-induced ototoxicity is investigated in this study. METHODS: Cisplatin intraperitoneally injected C57BL/6 mice were trans-tympanically administered BMSC-Exo or hypBMSC-Exo in the left ear. Myosin 7a staining was utilized to detect mature hair cells. Auditory brainstem response (ABR) was assessed to indicate auditory sensitivity at 8, 16, 24, and 32 kHz. The relative expressions of hypoxia-inducible factor-1α (HIF-1α), superoxide dismutase 1 (SOD1), and SOD2 were determined with RT-PCR and Western blot. The content of hydrogen peroxide (H2O2), malondialdehyde (MDA), SOD, and glutathione (GSH) in the middle turns of the cochlea were measured. RESULTS: Up-regulated HIF-1α expression was observed in hypBMSC-Exo compared with BMSC-Exo. Diminished auditory sensitivity and increased hair cell loss was observed in the cisplatin-exposed mice with increased content of H2O2 and MDA and decreased content of SOD and GSH, which could be reversed by hypBMSC-Exo or BMSC-Exo administration. It is worth noting that hypBMSC-Exo demonstrated more treatment benefits than BMSC-Exo with up-regulated SOD1 and SOD2 expression in the middle turns of the cochlea tissues. CONCLUSIONS: Hypoxic preconditioning may provide a new therapeutic option in regenerative medicine, and hypBMSC-Exo could be utilized to alleviate cisplatin-induced ototoxicity.

[The application value of video head impulse test, caloric test and dizziness handicap inventory in the diagnosis of acoustic neuroma].

Objective:To explore the application value of video head impulse test（vHIT）, caloric test（CT） and the dizziness handicap inventory（DHI） in the diagnosis of acoustic neuroma（AN）, to analyze the correlation between vHIT and CT, and to determine the correlationsof tumor size, vHIT, CT and DHI score. Methods:The clinical data of 24 patients with AN who underwent surgery in our department from January 2019 to January 2022 were analyzed retrospectively, including craniocerebral MRI, vHIT, caloric test and DHI score. All the data were statistically analyzed by GraphPadPrism9.0. Results:There was a significant negative correlation between the UW value of CT and the vestibular eye reflex gain of vHIT（P<0.01, r=-0.62）. The tumor size was significantly correlated with the increase of UW value of CT（P<0.01, r=0.69）, and with the decrease of vestibulo-ocular reflex gain of vHIT（P<0.01, r=-0.53）. The average Dizziness Handicap Inventory score was 8.9±16.2, which was not correlated with tumor size（P>0.05）. Conclusion:Both vHIT and CT can effectively evaluate the vestibular function of patients with AN（and they are complementary）, and they are related to the size of the tumor and have certain value in the diagnosis of acoustic neuroma.

Up-Regulated Expression of Interferon-Gamma, Interleukin-6 and Tumor Necrosis Factor-Alpha in the Endolymphatic Sac of Meniere's Disease Suggesting the Local Inflammatory Response Underlies the Mechanism of This Disease.

Background: Immune mediated inflammatory changes affecting the endolymphatic sac (ES) may underlie the pathology of Meniere's disease (MD). The aim of the present study was to explore the differentially expressed cytokines in ES luminal fluid (ELF) of patients with MD, and the correlation between the expression of cytokines in the ELF with that in the serum was determined by quantitatively analyzing the cytokines in human ELF and serum. Methods: Human ELF, serum and ES tissues were collected from patients with unilateral MD and patients with acoustic neuroma (AN) during surgery. The Simoa Cytokine 6-Plex Panel kit was used to analyze the levels of cytokines in the ELF and blood samples of the patients. Immunohistochemistry and immunofluorescence were subsequently used to validate the relative expression levels of the cytokines in MD. Results: Significant differences were identified in the expression levels of interferon-γ (IFN-γ) (P < 0.001), interleukin (IL)-6 (P = 0.008) and tumor necrosis factor-α (TNF-α) (P = 0.036) in the luminal fluid of the ES comparing between the MD and AN groups. By contrast, the levels of IFN-γ, IL-10, IL-12p70, IL-17A, IL-6 and TNF-α in the serum of the MD group were not significantly different from those of either the AN group or healthy control subjects. In addition, no significant correlations in the expression levels of cytokines compared between the ELF and serum were found for the patients in either the MD or the AN group. Finally, the detection of positive expression of TNF-α, IL-6 and IFN-γ in the epithelial cells of the majority of ES specimens from patients with MD confirmed the up-regulated expression of these cytokines in the ES of patients with MD. Conclusions: The identification of up-regulated expression levels of TNF-α, IL-6 and IFN-γ in the ELF in the present study has provided direct evidence for an increased immunologic activity in the microenvironment of the ES in patients with unilateral MD, may suggest the local inflammatory response underlies the mechanism of this disease.

Study on the treatment of traumatic orbital apex syndrome by nasal endoscopic surgery.

Orbital apex syndrome (OAS) is a complex disease caused by a variety of pathological factors, and trauma is one of the main factors/causes. Clinical data of 17 cases of traumatic OAS treated by nasal endoscopic surgery in our department from January 2002 to April 2009 were gathered and reviewed. Among them, the six patients presented with OAS after injury to the lateral wall of orbital apex. Seven other patients exhibited OAS after injury to the medial wall of orbital apex, two displayed OAS after zygomatic trauma, while OAS manifested in the other two patients with craniocerebral trauma 3 days after they had decompressive craniotomy--of them, one was blind in both eyes. In the 17 cases, 6 patients were without light sensation, 1 was blind in both eyes; the sight-chart index of eight patients was 0.1, that of three other patients was 0.1-0.2. Fifteen patients displayed eyeball movement disturbance (disorder) and cornea sensory disturbance (disorder), two were with the eyeball abducent disturbance. After the nasal endoscopic surgeries for OAS performed on the 17, the sight of the most patients was restored in varying degrees. The sight of nine patients was between 0.2 and 0.3, that of two patients was between 0.1 and 0.2, that of the other two patients was 0.1, and that of four patients remained unchanged. The eyeball movement and the cornea esthesia in 15 patients recovered from the surgeries, one patient recovered with good eyeball adducent movement and the cornea esthesia but with eyeball abducent disturbance, the other patient did not make a recovery from the eyeball immobility, cornea anesthesia and ptosis. A follow-up lasting 2 months to 2 years suggested that the 16 patients had stable recovery from the surgeries. Satisfactory results could be achieved in the treatment of traumatic OAS by nasal endoscopic surgery. From objective assessment of the therapeutic effects of traumatic OAS, it can be concluded that if a patient is diagnosed with fractures of the optic canal and the superior and medial walls of orbital apex, nasal endoscopic decompression of superior and medial walls of orbital apex and optic canal via the approach to the sphenoid and ethmoid sinuses is the most ideal operative therapy.

[Expression of proteinase TMPRSS3 in mouse cochlea].

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.

[Expression of TMPRSS3 in the rat cochlea following kanamycin ototoxicity].

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.

Identification of Novel Prognostic Markers Associated With Laryngeal Squamous Cell Carcinoma Using Comprehensive Analysis.

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is a leading malignant cancer of the head and neck. Patients with LSCC, in which the cancer has infiltrated and metastasized, have a poor prognosis. Therefore, there is an urgent need to identify more potential targets for drugs and biomarkers for early diagnosis. METHODS: RNA sequence data from LSCC and patients' clinical traits were obtained from the Gene Expression Omnibus (GEO) (GSE142083) and The Cancer Genome Atlas (TCGA) database. Differentially expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify hub genes. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, prognostic value analysis, receiver operating characteristic (ROC) curve analysis, gene mutation analysis, tumor-infiltrating immune cell abundance profile estimation, gene set variation analysis (GSVA), and gene set enrichment analysis (GSEA) were performed. Single-gene RNA sequencing data were obtained from the GSE150321 dataset. Cell proliferation and viability were confirmed by the CCK-8 assay and real-time PCR. RESULTS: A total of 701 DEGs, including 329 upregulated and 372 downregulated genes, were screened in the GSE142083 dataset. Using WGCNA, three modules were identified to be closely related to LSCC. After intersecting the DEGs and performing univariate and multivariate Cox analyses, a novel prognostic model based on three genes (SLC35C1, HOXB7, and TEDC2) for LSCC was established. Interfering TEDC2 expression inhibited tumor cell proliferation and migration. CONCLUSIONS: Our results show that SLC35C1, HOXB7, and TEDC2 have the potential to become new therapeutic targets and prognostic biomarkers for LSCC.

A comparison of endolymphatic duct blockage, endolymphatic sac drainage and endolymphatic sac decompression surgery in reversing endolymphatic hydrops in Meniere's disease.

BACKGROUND: To explore the differences between endolymphatic duct blockage, endolymphatic sac drainage and endolymphatic sac decompression surgery in the reversal of endolymphatic hydrops (EH) in patients with intractable Meniere's disease (MD). METHODS: A total of 27 MD patients receiving endolymphatic duct blockage surgery (n = 10), endolymphatic sac drainage surgery (n = 9) and endolymphatic sac decompression surgery (n = 8) underwent gadolinium-enhanced inner ear magnetic resonance imaging (MRI) scans prior to, 2 weeks after and at > 12 months following surgery. RESULTS: In the group with endolymphatic duct blockage, the second MRI revealed no changes in EH, whereas the third MRI revealed a reversal of vestibular EH in 3 patients and a downgrading of cochlear hydrops in 2 of these 3 patients, who presented with an improvement in their hearing and complete control of vertigo. In the group with endolymphatic sac drainage, the second MRI showed a reversal of EH in 4 patients, and no changes in EH in the remaining 5 patients, whereas the third MRI showed that those 4 patients who presented with a reversal of EH at the second MRI stage remained unchanged except a recurrence of vestibular hydrops in 1 patient. All 4 patients exhibited a complete control of vertigo, but hearing improved in 1, worsened in 1 and remained unchanged in 2. In the group with endolymphatic sac decompression, both the second and third MRI examination revealed no reversal of EH. CONCLUSIONS: The present study has shown that both endolymphatic duct blockage surgery and endolymphatic sac drainage surgery have the potential to reduce EH in certain MD patients, but none of the patients receiving endolymphatic sac decompression surgery showed reversal of their EH.