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Objective:Immunity is associated with acute low tone hearing loss. However, the exact pathophysiology of immunity-mediated acute low tone hearing loss remains unknown. In this study, we evaluated the presence, therapeutic effectiveness, and immunopathological mechanisms of anti-endothelial cell autoantibodies (AECEs) in patients with acute low-frequency hearing loss.Material and Methods:Forty-nine patients who were treated as inpatients having acute low-frequency hearing loss and additional symptoms, such as ear fullness, tinnitus, dizziness, or hyperacusis, were enrolled in this study. Serum samples from these patients were collected for laboratory serum autoimmunity detection, including AECAs, antinuclear antibodies, immunoglobulin, and circular immune complex. Therapeutic responses to combination therapy in short-term outcome and serum cytokine levels were compared between AECA-positive and AECA-negative patients.Results:Anti-endothelial cell autoantibodies–positive patients tended to show significantly less response to standard therapy compared with AECAs controls ( P < .05). Moreover, some serum cytokine levels elevated in both AECAs− and AECAs+ groups. Positive ratio of interleukin-8 and concentrations of macrophage inflammatory protein-1α were found higher in AECAs+ groups ( P < .05).Conclusion:The results supported that AECAs might wield influence on the short-term outcome of acute low-tone hearing loss (ALHL) treatment. Furthermore, AECA-mediated acute low-frequency hearing loss possibly involved dysregulation of inflammation process and release of cytokines.

Background. The precise mechanisms of nerve regeneration remain unclear. The potential of facial nerve regeneration and probable mechanisms involved following chronic facial nerve injury should be further studied. Methods. Adult male Wistar rats were used to model either (i) facial nerve injury (axotomy) or (ii) reinjury (chronic axotomy followed by a second axotomy within 5 months). The rats were housed in the animal facility of the Eye and ENT Hospital of Shanghai Medical School, Fudan University (Shanghai, China). Expression of Shh (sonic hedgehog) and growth-associated protein 43 (GAP43, a neuronal marker) was detected in bilateral facial nuclei using reverse transcriptase PCR, western blotting analysis, and immunohistochemistry. The number of surviving motoneurons was quantified, and facial nerve regeneration was examined using transmission electron microscopy. Results. Reinjury of the facial nerve 12 weeks after the first axotomy resulted in upregulation of GAP43 mRNA and protein expression in neurons ipsilateral to the axotomy; immunohistochemistry revealed that Shh expression was higher compared with control side facial nuclei at the same time point. GAP43 expression subsequently decreased. Conclusion. The greatest regeneration potential of the facial nerve occurred within 5 months following chronic axotomy in rats, and regeneration may involve the Shh signaling pathway.

Objective: To study the clinical anatomy of the epitympanum, the attic, and its medial wall, to try to discover a new clinical operation-related anatomical landmark, and to investigate the adjacent anatomical relationship with this landmark. Materials and Methods: Eight donor temporal bone specimens were dissected endoscopically. For 29 healthy persons (17 males and 12 females), CT images of the temporal bone (57 ears) were taken, 3-dimensional (3-D) reconstruction and multidimensional plane reconstruction were performed, and identification and assessment of 3-D spatial relationships between any 2 of these complex structures were done. Results: 3-D images of the temporal bone structures including the facial nerve, the cochlea, the semicircular canal, and the brain plate were reconstructed and shown in detail. We discovered a new clinical surgery-related anatomical landmark (the “cog” tangent and the trailing edge of the cog). Based on the tangent and the trailing edge of the cog, we quantified the anatomical relationship between it and its neighboring important structures. Conclusion: Based on endoscopic anatomy and the temporal bone spiral CT 3-D structure reconstruction of the epitympanum, the attic, and the adjacent structures, we found an extension of the clinical significance the cog. Quantification of the adjacent anatomical relationship of this landmark is very important for otology microsurgical operation.

Background/Purpose: To retrospectively analyze the epidemiological features, clinical diagnosis, and treatment of 610 patients with maxillofacial fractures, while providing a reference for the prevention and optimized treatment of maxillofacial fractures. Methods: Data of patients with maxillofacial fractures who were treated and followed up at the Second People’s Hospital of Kashi Prefecture from June 2012 to April 2018 were summarized. The epidemiological features, clinical manifestations, fracture sites, treatment methods, and results were analyzed. Results: The highest incidence was in the age range of 20 to 49 years. The main cause of fracture was traffic injury. Mandibular fractures accounted for 37.77%, zygoma and zygomatic arch fractures for 37.00%, and maxillary fractures for 21.19%. Atypical zygomatic arch fractures were more common in the maxilla, followed by Le Fort I and II fractures. Closed fractures accounted for 85.97%. Many (73.39%) patients were treated with computed tomography 3-dimensional (3D)-mediated precision modified incision internal fixation with satisfactory results. Conclusions: There is a high incidence of maxillofacial fractures among young men, especially in summer, with the most common injuries being traffic-related injuries. The most common site is the mandible, followed by the zygomatic arch, zygomatic complex, and maxilla. Computed tomography 3D-mediated precision modified incision internal fixation can achieve satisfactory results.

The loss of sensory hair cells in the cochlea is the major cause of sensorineural hearing loss, and inflammatory processes and immune factors in response to cochlear damage have been shown to induce hair cell apoptosis. The expression and function of Nfatc4 in the cochlea remains unclear. In this study, we investigated the expression of Nfatc4 in the mouse cochlea and explored its function using Nfatc4−/− mice. We first showed that Nfatc4 was expressed in the cochlear hair cells. Cochlear hair cell development and hearing function were normal in Nfatc4−/− mice, suggesting that Nfatc4 is not critical for cochlear development. We then showed that when the hair cells were challenged by ototoxic drugs Nfatc4 was activated and translocated from the cytoplasm to the nucleus, and this was accompanied by increased expression of Tnf and its downstream targets and subsequent hair cell apoptosis. Finally, we demonstrated that Nfatc4-deficient hair cells showed lower sensitivity to damage induced by ototoxic drugs and noise exposure compared to wild type controls. The Tnf-mediated apoptosis pathway was attenuated in Nfatc4-deficient cochlear epithelium, and this might be the reason for the reduced sensitivity of Nfatc4-deficient hair cells to injury. These findings suggest that the amelioration of inflammation-mediated hair cell apoptosis by inhibition of Nfatc4 activation might have significant therapeutic value in preventing ototoxic drug or noise exposure-induced sensorineural hearing loss.

To explore the structural characteristics of the cochlea in three-dimensional (3D) detail using 3D micro-computed tomography (mCT) image reconstruction of the osseous labyrinth, with the aim of improving the structural design of electrodes, the selection of stimulation sites, and the effectiveness of cochlear implantation. Three temporal bones were selected from among adult donors' temporal bone specimens. A micro-CT apparatus (GE eXplore) was used to scan three specimens with a voxel resolution of 45 μm. We obtained about 460 slices/specimen, which produced abundant data. The osseous labyrinth images of three specimens were reconstructed from mCT. The cochlea and its spiral characteristics were measured precisely using Able Software 3D-DOCTOR. The 3D images of the osseous labyrinth, including the cochlea, vestibule, and semicircular canals, were reconstructed. The 3D models of the cochlea showed the spatial relationships and surface structural characteristics. Quantitative data concerning the cochlea and its spiral structural characteristics were analyzed with regard to cochlear implantation. The 3D reconstruction of mCT images clearly displayed the detailed spiral structural characteristics of the osseous labyrinth. Quantitative data regarding the cochlea and its spiral structural characteristics could help to improve electrode structural design, signal processing, and the effectiveness of cochlear implantation. Clin. Anat. 30:39-43, 2017. © 2016 Wiley Periodicals, Inc.

To explore the feasibility of constructing a functional biomaterial complex with regenerated silk fibroin membrane and immortalized chondrocytes in vivo. Rat auricular chondrocytes (RACs) were transfected with the lentivirus vector pGC-FU-hTERT-3FLAG or pGC-FU-GFP-3FLAG, encoding the human telomerase reverse transcriptase (hTERT) or GFP gene. The effects of regenerated silk fibroin film on the adhesion, growth of immortalized chondrocytes and expression of collagen II in vitro were analyzed with immunofluorescent histochemistry. Immortalized RACs were transformed. Induction by nutrient medium promoted higher expression levels of collagen II in transformed chondrocytes. The regenerated silk fibroin film was not cytotoxic to immortalized chondrocytes and had no adverse influence on their adhesion. Collagen II expression was good in the immortalized chondrocytes in vivo. The construction of a silk-based biomaterial complex with immortalized chondrocytes may provide a feasible kind of functional biomaterial for the repair of cartilage defects in clinical applications. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1071–1078, 2014.

Objectives To explore the feasibility of silk fibroin as a biomaterial coating used in tracheal defect reconstruction. Methods Silk fibroin was subcutaneously embedded in three rabbits and as an artificial implant material coating to reconstruct 12 rabbits' tracheal defects. The postoperative radiologic and histologic characterization was summarized. Results The thickness of the fibroblasts layer covering the porus and nonporus silk fibroin film was 240.4 ± 9.9 and 302.3 ± 10.5 μm, respectively, and there was no statistical difference (P > 0.05) within each group. There was no foreign-body granuloma or macrophagocyte infiltration around the silk film. The tracheal reconstruction study showed a normal mucous membrane with normal cilial growth on the artificial implant and no visible granulation tissue in the reconstructed tracheal cavity. Conclusions Silk fibroin is a potential new biomaterial coating for tracheal defect reconstruction. The mechanism of silk fibroin appears to promote tracheal mucous membrane, which may be related to its molecular structure and biology.

Endolymphatic sac tumors (ELSTs) are locally invasive, osteolytic, and hypervascular tumors. If the labyrinth has not been invaded, the hearing should be preserved in operation.To summarize three cases of ELST and discuss whether to keep hearing in the surgical treatment of ELST.Complete otorhinolaryngological examinations with audiologic, vestibular, and neurologic evaluations were performed. CT and MRI scans were carried out before operation and in the course of follow-up. The patients underwent radical removal of the tumor through a transmastoid approach and accepted postoperative radiotherapy. In two of them, the structure of the labyrinth and facial nerve were preserved in operation.Histopathologic examinations agreed with features of an ELST. Patients suffered transitory vertigo shortly after operation, and so far, they are alive and well without further cranial nerve involvement. Case 3 patient has good hearing and facial nerve function now. No residual or recurrent tumor was detected on the postoperative MRI images.

One of the most unfortunate side effects of aminoglycoside (AG) antibiotics such as neomycin is that they target sensory hair cells (HCs) and can cause permanent hearing impairment. We have observed HC loss and microglia-like cell (MLC) activation in the inner ear (cochlea) following neomycin administration. We focused on CX3CL1, a membrane-bound glycoprotein expressed on neurons and endothelial cells, as a way to understand how the MLCs are activated and the role these cells play in HC loss. CX3CL1 is the exclusive ligand for CX3CR1, which is a chemokine receptor expressed on the surface of macrophages and MLCs. In vitro experiments showed that the expression levels of CX3CL1 and CX3CR1 increased in the cochlea upon neomycin treatment, and CX3CL1 was expressed on HCs, while CX3CR1 was expressed on MLCs. When cultured with 1 μg/mL exogenous CX3CL1, MLCs were activated by CX3CL1, and the cytokine level was increased in the cochleae leading to apoptosis in the HCs. In CX3CR1 knockout mice, a significantly greater number of cochlear HCs survived than in wild-type mice when the cochlear explants were cultured with neomycin in vitro. Furthermore, inhibiting the activation of MLCs with minocycline reduced the neomycin-induced HC loss and improved the hearing function in neomycin-treated mice in vivo. Our results demonstrate that CX3CL1-induced MLC activation plays an important role in the induction of HC death and provide evidence for CX3CL1 and CX3CR1 as promising new therapeutic targets for the prevention of hearing loss.

After the surgical procedure of ossicular chain reconstruction, the effectiveness and/or stability of partial ossicular replacement prosthesis (PORP) or total ossicular replacement prosthesis (TORP) were systematically compared and evaluated using meta-analysis. A total of 40 eligible investigations with 4,311 subjects were included in our study. There was a significant difference in the effectiveness of the reconstruction of the ossicular chain between PORP and TORP; the data showed a combined risk ratio (RR) of 1.28 (95 % CI 1.17–1.41, p < 0.00001), but no notable difference was obtained in staged procedures subgroup and cholesteatoma subgroup, with a combined RR of 1.13 (95 % CI 0.60–2.11, p = 0.70) in staged procedures subgroup and RR of 2.60 (95 % CI 0.20–36.21, p = 0.59 in cholesteatoma subgroup). There was a statistically significant difference in the stability of the prostheses in long-term follow-up, with a combined RR of 0.37 (95 % CI 0.16–0.85, p = 0.02), but no significant difference was observed in the total sample, with a combined RR of 0.64 (95 % CI 0.40–1.03, p = 0.06). Our overall results suggest that the effectiveness of PORP was higher than TORP, except within staged procedures subgroup and cholesteatoma subgroup. In addition, the stability of PORP was significantly superior to TORP in long-term follow-ups, but no significant effect was detected in the general study.

Objective To investigate an effective method of quantitative analysis of the facial nerve and its adjacent structures on the basis of three-dimensional (3D) CT image reconstruction of the temporal bone. Methods The inner structures of the temporal bone from CT images of 34 healthy adults were reconstructed. Precise measurement of the facial nerve and its adjacent structures were accomplished by using Able Software 3D-DOCTOR. Results 3D images of temporal bone structures, including facial nerve, tympanic annulus, cochleariform process, cochlea, semicircular canals, jugular fossa, and carotid artery, were reconstructed. Quantitative data of the facial nerve and its adjacent structures were analyzed, especially the detailed spatial relationships between the facial nerve and the surface of the mastoid process or tympanomastoid fissure. Conclusion 3D reconstruction of CT images clearly displayed the detailed structures of the temporal bone. Quantitative data of the facial nerve and its adjacent structures are very useful for temporal bone surgery.