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.

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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.

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.

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.

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 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.

Objective: To characterize the morphology of chondrocytes and the expression and secretion of active collagen II by these cells cultured within a regenerated silk fibroin film. Silk fibroin film cytocompatibility and the effect of silk fibroin on chondrocytes in vitro were also evaluated. Methods: Chondrocytes were transfected with a lentivirus containing a green fluorescent protein marker and cultured within a regenerated silk fibroin film. Effects on chondrocyte adhesion, growth, and expression of functional collagen II were assessed in vitro by analysis with immunofluorescent histochemistry and laser scanning confocal microscopy. Results: The results of this study showed that the regenerated silk fibroin film had no cytotoxic effect on chondrocytes. The regenerated silk fibroin film facilitated the adhesion of chondrocytes with typical morphology. Chondrocytes cultured within silk fibroin films exhibited the expression of collagen II in vitro. Conclusion: Regenerated silk fibroin film was found to be an excellent biomaterial with good cytocompatibility for chondrocytes, because these cells remained functional and maintained normal cell morphology when cultured in silkbased biomaterials. These results suggest that silk-based chondrocyte biomaterial complexes may provide a feasible and functional biomaterial for repairing clinical cartilage defects.