Inhibition of histone methyltransferase PRMT5 attenuates cisplatin-induced hearing loss through the PI3K/Akt-mediated mitochondrial apoptotic pathway / 药物分析学报

This study aimed to evaluate the therapeutic potential of inhibiting protein arginine methyltransferase 5(PRMT5)in cisplatin-induced hearing loss.The effects of PRMT5 inhibition on cisplatin-induced auditory injury were determined using immunohistochemistry,apoptosis assays,and auditory brainstem response.The mechanism of PRMT5 inhibition on hair cell survival was assessed using RNA-seq and Cleavage Under Targets and Tagment-quantitative polymerase chain reaction(CUT&Tag-qPCR)analyses in the HEI-OC1 cell line.Pharmacological inhibition of PRMT5 significantly alleviated cisplatin-induced damage to hair cells and spiral ganglion neurons in the cochlea and decreased apoptosis by protecting mitochondrial function and preventing the accumulation of reactive oxygen species.CUT&Tag-qPCR analysis demonstrated that inhibition of PRMT5 in HEI-OC1 cells reduced the accumulation of H4R3me2s/H3R8me2s marks at the promoter region of the Pik3ca gene,thus activating the expression of Pik3ca.These findings suggest that PRMT5 inhibitors have strong potential as agents against cisplatin-induced ototoxicity and can lay the foundation for further research on treatment strategies of hearing loss.

Inhibiting DNA methylation alleviates cisplatin-induced hearing loss by decreasing oxidative stress-induced mitochondria-dependent apoptosis via the LRP1-PI3K/AKT pathway

Cisplatin-related ototoxicity is a critical side effect of chemotherapy and can lead to irreversible hearing loss. This study aimed to assess the potential effect of the DNA methyltransferase (DNMT) inhibitor RG108 on cisplatin-induced ototoxicity. Immunohistochemistry, apoptosis assay, and auditory brainstem response (ABR) were employed to determine the impacts of RG108 on cisplatin-induced injury in murine hair cells (HCs) and spiral ganglion neurons (SGNs). Rhodamine 123 and TMRM were utilized for mitochondrial membrane potential (MMP) assessment. Reactive oxygen species (ROS) amounts were evaluated by Cellrox green and Mitosox-red probes. Mitochondrial respiratory function evaluation was performed by determining oxygen consumption rates (OCRs). The results showed that RG108 can markedly reduce cisplatin induced damage in HCs and SGNs, and alleviate apoptotic rate by protecting mitochondrial function through preventing ROS accumulation. Furthermore, RG108 upregulated BCL-2 and downregulated APAF1, BAX, and BAD in HEI-OC1 cells, and triggered the PI3K/AKT pathway. Decreased expression of low-density lipoprotein receptor-related protein 1 (LRP1) and high methylation of the LRP1 promoter were observed after cisplatin treatment. RG108 treatment can increase LRP1 expression and decrease LRP1 promoter methylation. In conclusion, RG108 might represent a new potential agent for preventing hearing loss induced by cisplatin via activating the LRP1-PI3K/AKT pathway.

Research progress on three-dimensional printed interbody fusion cage / 生物医学工程学杂志

Spinal fusion is a standard operation for treating moderate and severe intervertebral disc diseases. In recent years, the proportion of three-dimensional printing interbody fusion cage in spinal fusion surgery has gradually increased. In this paper, the research progress of molding technology and materials used in three-dimensional printing interbody fusion cage at present is summarized. Then, according to structure layout, three-dimensional printing interbody fusion cages are classified into five types: solid-porous-solid (SPS) type, solid-porous-frame (SPF) type, frame-porous-frame (FPF) type, whole porous cage (WPC) type and others. The optimization process of three-dimensional printing interbody fusion cage and the advantages and disadvantages of each type are analyzed and summarized in depth. The clinical application of various types of 3D printed interbody fusion cage was introduced and summarized later. Lastly, combined with the latest research progress and achievements, the future research direction of three-dimensional printing interbody fusion cage in molding technology, application materials and coating materials is prospected in order to provide some reference for scholars engaged in interbody fusion cage research and application.

Mechanism of Aurora-A to promote chemoresistance in nasopharyngeal carcinoma / 中国耳鼻咽喉头颈外科

OBJECTIVE To explore the mechanism of Aurora kinase A (Aurora-A) promoting cancer cell chemotherapy resistance in nasopharyngeal carcinoma. METHODS The expression of Aurora-A in nasopharyngeal carcinoma tissues and adjacent tissues were detected by Western bolt and Q-PCR. The highexpressing Aurora A cell line CNE2 was used to detected the cell apoptosis and the expression of key pathway marker protein after Aurora-A inhibitor VX680 and cisplatin treatment by using Flow cytometry and WB. RESULTS The expression of Aurora-A in nasopharyngeal carcinoma tissues was significantly higher than that in adjacent tissues. Comparing to normal nasopharyngeal cells NP69, Aurora-A was significantly highly expressed in all of nasopharyngeal carcinoma cells and was highest in CNE2. Inhibiton of Aurora-A increased the cell apoptosis and the expression of p-AKT, p21 and Cleaved-Caspase-3 after using cisplatin or the Aurora-A inhibitor VX680 treatment. CONCLUSION The results shown that Aurora-A confer chemoresistance to cisplatin treatment through p-AKT/p21/Cleaved-Caspase-3 pathway.

Idenfication of microRNAs profiles in nasopharyngeal carcinoma / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To filtrate and prove the different microRNAs (miRs) profiles in nasopharyngeal carcinoma.@*METHOD@#Screening the different expressions of miRs between nasopharyngeal carcinoma and the inflammatory tissues by the application of expression profiling of chip high-throughput and large-scale microarray analysis. Then we used RT-QPCR technology to prove the accuracy of screening results.@*RESULT@#There were significant expression differences of miRs between nasopharyngeal carcinoma and the control tissues, 144 human miRs had 2 or more fold the difference ratio. Compared with the inflammatory tissues, we have found that miRs-34b, miRs-449b and miRs-7-1 significantly low expressed in nasopharyngeal carcinoma, yet miRs-125b, miRs-184, miRs-196b, miRs-205 and miRs-24-1 expressed high. The results were consistent with the microarray analysis.@*CONCLUSION@#The difference expressed miRs might be closely related to the process of nasopharyngeal carcinoma, and the research on miRs profiles maybe provide a powerful target basis for early diagnosis and therapy of nasopharyngeal carcinoma.

CDK3 expression and its clinical significance in human nasopharyngeal carcinoma / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To investigate the expression profile and the clinical significance of CDK3 in the tissues of nasopharyngeal carcinoma.@*METHOD@#Immunohistochemistry was utilized to detect the expression of CDK3 in 94 cases of NPC and 40 cases of nasopharyngeal inflammation.@*RESULT@#CDK3 was highly expressed in NPC cell lines. Immunohistochemistry showed that CDK3 was mostly expressed in the cytoplasm. The positive expression rate of NPC was 67% and that of nasopharyngeal inflammation was only 12. 5%. The difference between these two groups was highly statistically significant. The CDK3 expression in NPC was related to the TNM clinical staging of NPC (P < 0.01).@*CONCLUSION@#The expression levels of CDK3 were obviously higher in NPC tissues. The CDK3 expression in NPC was related to the TNM clinical staging of NPC. It suggests that CDK3 expression may play an important role in the occurrence and development of nasopharyngeal carcinoma.

Treatment of infection in posterior tympani cavity during surgical procedures of otitis media / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#Analyse the effect of the treatment of infection in posterior tympani cavity in 168 cases with chronic otitis media.@*METHOD@#Infection was eliminated in posterior tympani cavity of all 168 cases after surgical procedures of otitis media, and 102 tympanoplasty with autoplastic bone were operated in all cases. 22 tympanoplasty were operated without mastoidectomy, 53 with transmastoid approach, 27 with mastoidectomy and tympanoplasty.@*RESULT@#All cases were followed up for more than one year. 160 cases were cured, the effective rate was 95% and no recurrence appeared except for 8 cases. The average threshold of hearing improvement of 87 cases > 15 dB, the effective rate was 85%.@*CONCLUSION@#To eliminate infection, the exploratory surgery of posterior tympani cavity should be done during surgical procedures of otitis media, for improving the effect of the treatment of otitis media.

The value of loop-mediated isothermal amplification method for rapid diagnosis of EBV DNA / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#To establish a rapid method for EBV detection with loop-mediated isothermal amplification (LAMP), and to make it as a clue for early diagnosis of nasopharyngeal carcinoma cancer.@*METHOD@#EBV DNA was fast extracted from samples after boiling, while the whole detection will be finished within an hour with specific amplification of EBV gene by LAMP.@*RESULT@#High specificity was shown from EBV detection of 33 clinical samples. Comparing with PCR, LAMP is more simple and convenient to perform under isothermal conditions, and require no special apparatus, thus, it is more economical and practical.@*CONCLUSION@#LAMP analysis of EBV may be an efficient and easy way for clinical diagnosis of nasopharyngeal carcinoma.

Electron Microscopic Autoradiography in Inner Ear Pathological Study / 听力学及言语疾病杂志

Objective To evaluate the technique of electron microscopic autoradiography in inner ear pathology.Methods The thin sections that was labeled with the thymidine-H3(3H-TdR)were prepared.The labeled specimen were processed for electron microscopic autoradiography(EM-ARG)after treatment with emulsions,development and fixation.Results Incorporation of 3H-TdR was seen over regenerated cells in the experimental papilla in regions of hair cell loss.Conclusion This methocl gives a good localization of the label at the ultrastructural level.