ML162 derivatives incorporating a naphthoquinone unit as ferroptosis/apoptosis inducers: Design, synthesis, anti-cancer activity, and drug-resistance reversal evaluation.

Activating apoptosis has long been viewed as an anti-cancer process, but recently increasing evidence has accumulated that induction of ferroptosis has emerged as a promising strategy for cancer therapeutics. Glutathione peroxidase 4 (GPX4) is one of the pivotal factors regulating ferroptosis that targeted inhibition or degradation of GPX4 could effectively trigger ferroptosis. In this study, a series of ML162-quinone conjugates were constructed by using pharmacophore hybridization and bioisosterism strategies, with the aim of obtaining more active anticancer agents via the ferroptosis and apoptosis dual cell death processes. Of these compounds, GIC-20 was identified as the most active one that exhibited promising anticancer activity both in vitro and in vivo via ferroptosis and apoptosis dual-targeting processes, without obvious toxicity compared with ML162. On one hand, GIC-20 could trigger ferroptosis in cells by inducing intracellular lipid peroxide and ROS accumulation, and destroying mitochondrial structure. In addition to GPX4 inhibition, GIC-20 can also trigger ferroptosis via proteasomal-mediated degradation of GPX4, suggesting GIC-20 may function as a molecule glue degrader. On the other hand, GIC-20 can also induce apoptosis via upregulating the level of apoptotic protein Bax and downregulating the level of anti-apoptotic protein Bcl-2 in HT1080 cells. Furthermore, GIC-20 also enhanced the sensitivity of resistant MIA-PaCa-2-AMG510R cells to AMG510, suggesting the great potential of GIC-20 in overcoming the acquired resistance of KRASG12C inhibitors. Overall, GIC-20 represents a novel dual ferroptosis/apoptosis inducer warranting further development for cancer therapeutics and overcoming drug resistance.

Neuroprotection Role of Vitamin C by Upregulating Glutamate Transporter-1 in Auditory Cortex of Noise-Induced Tinnitus Animal Model.

Vitamin C (Vc) plays a pivotal role in a series of pathological processes, such as tumors, immune diseases, and neurological disorders. However, its therapeutic potential for tinnitus management remains unclear. In this study, we find that Vc relieves tinnitus in noise-exposed rats. In the 7-day therapy groups, spontaneous firing rate (SFR) increases from 1.17 ± 0.10 Hz to 1.77 ± 0.15 Hz after noise exposure. Vc effectively reduces the elevated SFR to 0.99 ± 0.07 and 0.55 ± 0.05 Hz at different doses. The glutamate level in auditory cortex of noise-exposed rats (3.78 ± 0.42 µM) increases relative to that in the control group (1.34 ± 0.22 µM). High doses of Vc (500 mg/kg/day) effectively reduce the elevated glutamate levels (1.49 ± 0.28 µM). Mechanistic studies show that the expression of glutamate transporter 1 (GLT-1) is impaired following noise exposure and that Vc treatment effectively restores GLT-1 expression in the auditory cortex. Meanwhile, the GLT-1 inhibitor, dl-threo-beta-benzyloxyaspartic acid (dl-TBOA), invalidates the protection role of Vc. Our finding shows that Vc substantially enhances glutamate clearance by upregulating GLT-1 and consequently alleviates noise-induced tinnitus. This study provides valuable insight into a novel biological target for the development of therapeutic interventions that may prevent the onset of tinnitus.

Synthesis and evaluation of WK-X-34 derivatives as P-glycoprotein (P-gp/ABCB1) inhibitors for reversing multidrug resistance.

The emergence of multidrug resistance (MDR) in malignant tumors is one of the leading threats encountered currently by many chemotherapeutic agents. A proposed strategy to overcome MDR is to disable the efflux function of P-glycoprotein (P-gp/ABCB1), a critical member of the ABC transporter family that significantly increases the efflux of various anticancer drugs from tumor cells. In this study, structural modification of a third-generation P-gp inhibitor WK-X-34 based on bioisosteric and fragment-growing strategies led to the discovery of the adamantane derivative PID-9, which exhibited the best MDR reversal activity (IC50 = 0.1338 µM, RF = 78.6) in this series, exceeding those of the reported P-gp inhibitors verapamil and WK-X-34. In addition, compared with WK-X-34, PID-9 showed decreased toxicity to cells. Furthermore, the mechanism studies revealed that the reversal activity of adamantane derivatives PID-5, PID-7, and PID-9 stemmed from the inhibition of P-gp efflux. These results indicated that compound PID-9 is the most effective P-gp inhibitor among them with low toxicity and high MDR reversal activity, which provided a fundamental structural reference for further discovery of novel, effective, and non-toxic P-gp inhibitors.

MSC-derived exosomes protect auditory hair cells from neomycin-induced damage via autophagy regulation

BACKGROUND: Sensorineural hearing loss (SNHL) poses a major threat to both physical and mental health; however, there is still a lack of effective drugs to treat the disease. Recently, novel biological therapies, such as mesenchymal stem cells (MSCs) and their products, namely, exosomes, are showing promising therapeutic potential due to their low immunogenicity, few ethical concerns, and easy accessibility. Nevertheless, the precise mechanisms underlying the therapeutic effects of MSC-derived exosomes remain unclear. RESULTS: Exosomes derived from MSCs reduced hearing and hair cell loss caused by neomycin-induced damage in models in vivo and in vitro. In addition, MSC-derived exosomes modulated autophagy in hair cells to exert a protective effect. Mechanistically, exogenously administered exosomes were internalized by hair cells and subsequently upregulated endocytic gene expression and endosome formation, ultimately leading to autophagy activation. This increased autophagic activity promoted cell survival, decreased the mitochondrial oxidative stress level and the apoptosis rate in hair cells, and ameliorated neomycin-induced ototoxicity. CONCLUSIONS: In summary, our findings reveal the otoprotective capacity of exogenous exosome-mediated autophagy activation in hair cells in an endocytosis-dependent manner, suggesting possibilities for deafness treatment.

Design and synthesis of proteolysis-targeting chimeras (PROTACs) as degraders of glutathione peroxidase 4.

Ferroptosis is a new type of regulated, non-apoptotic cell death driven by iron-dependent phospholipid peroxidation. Inducing cell ferroptosis by inactivating glutathione peroxidase 4 (GPX4) has been considered as an effective cancer treatment strategy, but only few GPX4 inhibitors have been reported to date. Targeted protein degradation is receiving increasing attention in the discovery and development of therapeutic modality, particularly proteolysis targeting chimeras (PROTACs). Herein, we reported the design, synthesis, and evaluation of different types of GPX4-targeting PROTACs using ML162 derivatives and ligands for CRBN/VHL E3 ligases. Among them, CRBN-based PROTAC GDC-11 showed a relatively balanced biological profile in GPX4 degradation (degradation rate of 33% at 10 µM), cytotoxicity (IC50 = 11.69 µM), and lipid peroxides accumulation (2-foldincreaserelatedtoDMSO), suggesting a typical characteristic of ferroptosis. In silico docking and quantum chemistry theoretical calculations provided a plausible explanation for the moderate degrading effect of these synthesized PROTACs. Overall, this work lays the foundation for subsequent studies of GPX4-targeting PROTACs, and further design and synthesis of GPX4-targeting degrader are currently in progress in our group, which will be reported in due course.

Tinnitus assessment: Chinese version of the Tinnitus Primary Function Questionnaire.

Objective: The aim of this study is to evaluate the Chinese Version of the Tinnitus Primary Function Questionnaire (TPFQ). Methods: One hundred and sixteen patients who had been suffering from tinnitus for over 3 months were included in this study. Those tinnitus patients were administered the TPFQ, the Tinnitus Handicap Inventory (THI), the Beck Anxiety Inventory (BAI), the Beck Depression Inventory (BDI), and the Pittsburgh Sleep Quality Index (PSQI). Additionally, the magnitude estimate of tinnitus loudness, pure tone audiogram, and tinnitus matching was obtained. The factor structure was measured using the Kaiser-Meyer-Olkin test. The internal consistency was examined using Cronbach's α coefficient. The relationships between the TPFQ scores and other measurements were compared using Spearman's rank correlation coefficient. Results: The Cronbach's α of the 20-item version of TPFQ was 0.94, and that of the 12-item version of TPFQ was 0.92. Both the 20- and 12-item versions of TPFQ were significantly correlated with magnitude estimation of tinnitus loudness, THI, PSQI, BDI, and BAI. The average pure tone hearing threshold was significantly correlated with the hearing subscale. Conclusion: The 20- and 12-item Chinese versions of TPFQ are reliable and valid measures of tinnitus. The TPFQ can be applied to the assessment and management of tinnitus among the Chinese-speaking population.

Deep learning-based approach for the automatic segmentation of adult and pediatric temporal bone computed tomography images.

Background: Automatic segmentation of temporal bone computed tomography (CT) images is fundamental to image-guided otologic surgery and the intelligent analysis of CT images in the field of otology. This study was conducted to test a convolutional neural network (CNN) model that can automatically segment almost all temporal bone anatomy structures in adult and pediatric CT images. Methods: A dataset comprising 80 annotated CT volumes was collected, of which 40 samples were obtained from adults and 40 from children. A further 60 annotated CT volumes (30 from adults and 30 from children) were used to train the model. The remaining 20 annotated CT volumes were employed to determine the model's generalizability for automatic segmentation. Finally, the Dice coefficient (DC) and average symmetric surface distance (ASSD) were utilized as metrics to evaluate the performance of the CNN model. Two independent-sample t-tests were used to compare the test set results of adults and children. Results: In the adult test set, the mean DC values of all the structures ranged from 0.714 to 0.912, and the ASSD values were less than 0.24 mm for 11 structures. In the pediatric test set, the mean DC values of all the structures ranged from 0.658 to 0.915, and the ASSD values were less than 0.18 mm for 11 structures. There was no statistically significant difference between the adult and child test sets in most temporal bone structures. Conclusions: Our CNN model shows excellent automatic segmentation performance and good generalizability for both adult and pediatric temporal bone CT images, which can help to advance otologist education, intelligent imaging diagnosis, surgery simulation, application of augmented reality, and preoperative planning for image-guided otology surgery.

[Expression and predictive value of type â ¡ inflammatory cytokines in nasal secretion in eosinophilic chronic rhinosinusitis with nasal polyps].

Objective:To analyze the expression of type Ⅱ inflammatory-related cytokines in nasal secretions of patients with eosinophilic chronic rhinosinusitis with nasal polyps（ECRSwNP）, and to preliminarily explore the role of type Ⅱ inflammatory cytokines in nasal secretions in predicting ECRSwNP. Methods:A prospective analysis was made of 91 patients with CRSwNP who underwent endoscopic sinus surgery in Peking University Third Hospital from November 2020 to June 2021. All the selected patients had their SNOT-22 score, Lund-Mackay score and blood eosinophilia collected before surgery. Percentage and absolute value; the nasal secretions of patients were collected before operation, and enzyme-linked immunosorbent assay was used to detect the typeⅡinflammatory cytokines（IL-4, IL-5, IL-13, IL-25, IL-33, Eotaxin-3, periostin）, intraoperative nasal polyp tissue was collected for eosinophil count. According to the proportion of eosinophils in the tissue≥10%, they were divided into ECRSwNP group and nECRSwNP group. The clinical baseline data and type Ⅱ inflammatory cytokines were compared between the two groups, and the related factors of ECRSwNP were evaluated by univariate logistic regression analysis. The receiver operating characteristic（ROC） curve was used to evaluate the predictive potential of each clinical index. Results:The SNOT-22 score, Lund-Mackay score, blood eosinophil percentage and absolute value in the ECRSwNP group were higher than those in the nECRSwNP group（P<0.05）. In the nECRSwNP group（P<0.01）. Logistic regression analysis found that IL-5, Eotaxin-3 and blood eosinophil percentage were risk factors for ECRSwNP（P<0.05）. ROC analysis found that IL-5, Eotaxin-3 and blood eosinophil percentage had predictive diagnostic value（P<0.01）, among which blood eosinophil percentage had the greatest predictive value（AUC=0.756）. The prediction model composed of Eotaxin-3, SNOT-22 score, sinus CT Lund-Mackay score, blood eosinophil percentage and blood eosinophil absolute value had better prediction effect on ECRSwNP（AUC=0.873）. Conclusion:Type Ⅱ inflammatory cytokines IL-5 and Eotaxin-3 in nasal secretions may be involved as biomarkers for early diagnosis of ECRSwNP.

Tissue eosinophils and mucous inflammatory cytokines for the evaluation of olfactory recovery after endoscopic sinus surgery in patients with nasal polyposis.

The etiologies of chronic rhinosinusitis with nasal polyps (CRSwNP)-associated olfactory dysfunction have several potentially overlapping hypotheses. Understanding the association of tissue eosinophils and mucous inflammatory cytokines with olfactory function and identifying predictors of olfactory outcomes in patients with nasal polyposis after surgery is fundamental for future clinical care and research. METHODS: Eighty-five patients who underwent endoscopic surgery for nasal polyposis were enrolled in this study. Olfactory measurements were performed before surgery and 3-6 months after surgery using a T&T olfactometer. Baseline characteristics of CRSwNP patients were collected, and Spearman's rho correlation was performed to assess the association of olfactory function with tissue eosinophils and mucous inflammatory cytokines. A multivariate logistic regression model was used to assess the independent predictors of olfactory outcomes after surgery. RESULTS: Here, 85 CRSwNP patients, including 25 patients without olfactory disorder and 60 patients with hypo-anosmia, were evaluated. Of the 60 patients with preoperative hypo-anosmia, 22 did not have improved olfactory function, and 38 demonstrated normal olfactory function after surgery based on the T&T olfactometer results. The levels of tissue eosinophil, interleukin-5 (IL-5), IL-13, eotaxin-3, and periostin in the preoperative hypo-anosmia group were higher than those in the preoperative normosmia group. Tissue eosinophil count, IL-5, and periostin levels in patients without olfactory improvement were higher than those in patients with olfactory improvement. The tissue eosinophil count, blood eosinophil count, and nasal mucus levels of IL-5, eotaxin-3, and periostin were significantly correlated with olfactory function in all patients with CRSwNP. The IL-5 level remained a strong predictor of poor olfactory outcomes after surgery. CONCLUSIONS: Both tissue eosinophils and mucous inflammatory cytokines, including IL-5, IL-13, eotaxin-3, and periostin, may contribute to the pathogenesis of CRSwNP-associated olfactory dysfunction. Higher IL-5 levels are associated with a lower chance of olfactory function recovery after each surgical revision.

Fully automated segmentation in temporal bone CT with neural network: a preliminary assessment study.

BACKGROUND: Segmentation of important structures in temporal bone CT is the basis of image-guided otologic surgery. Manual segmentation of temporal bone CT is time- consuming and laborious. We assessed the feasibility and generalization ability of a proposed deep learning model for automated segmentation of critical structures in temporal bone CT scans. METHODS: Thirty-nine temporal bone CT volumes including 58 ears were divided into normal (n = 20) and abnormal groups (n = 38). Ossicular chain disruption (n = 10), facial nerve covering vestibular window (n = 10), and Mondini dysplasia (n = 18) were included in abnormal group. All facial nerves, auditory ossicles, and labyrinths of the normal group were manually segmented. For the abnormal group, aberrant structures were manually segmented. Temporal bone CT data were imported into the network in unmarked form. The Dice coefficient (DC) and average symmetric surface distance (ASSD) were used to evaluate the accuracy of automatic segmentation. RESULTS: In the normal group, the mean values of DC and ASSD were respectively 0.703, and 0.250 mm for the facial nerve; 0.910, and 0.081 mm for the labyrinth; and 0.855, and 0.107 mm for the ossicles. In the abnormal group, the mean values of DC and ASSD were respectively 0.506, and 1.049 mm for the malformed facial nerve; 0.775, and 0.298 mm for the deformed labyrinth; and 0.698, and 1.385 mm for the aberrant ossicles. CONCLUSIONS: The proposed model has good generalization ability, which highlights the promise of this approach for otologist education, disease diagnosis, and preoperative planning for image-guided otology surgery.

[Application of deep learning assisted electronic laryngoscope in diagnosis of laryngeal leukoplakia].

In recent years, medical imaging technology and computer technology have made great progress. On the one hand, with the development and popularization of electronic laryngoscope, the image of electronic laryngoscope plays a very important role in the diagnosis of vocal cord lesions. On the other hand, deep learning algorithm，especially convolutional neural networkhas gradually become the first choice of medical image recognition since the foundation of deep learning algorithm. So far, deep learning algorithm has made great contributions in many disciplines. In this paper, the basic concept of deep learning, the current status of image recognition of vocal cord lesions, and the prospect of research based on deep learning in vocal cord image lesions recognition are reviewed.

[Causes analysis of mastoid cavity infection after mastoidectomy and key techniques of revision mastoidectomy].

Objective:To analyze the causes of infected mastoid cavity after mastoidectomy and explore the key techniques of revision mastoidectomy. Methods:Ninety-two patients, who underwent revision mastoidectomy due to mastoid cavity infection after mastoidectomy were retrospectively analyzed. There were 56 cases of canal wall up mastoidectomy plus tympanoplasty and 36 cases of canal wall down mastoidectomy plus tympanoplasty in previous surgery. The interval between the previous operation and this revision ranged from 7 months to 50 years, with a median of 9 years. By reviewing the general clinical data, preoperative HRCT scan of temporal bone and intraoperative findings, the defects of the previous operation and the region of the lesion were analyzed and counted. Results:Out of the 92 cases, 7 cases（7.6%） had sigmoid sinus antedisplacement and low-lying middle cranial fossa, and 45 cases（48.9%） with facial nerve canal loss. Among the 36 patients who underwent canal wall down mastoidectomy and tympanoplasty, mastoid cells were removed in completely; 26 patients had high facial ridge, accounting for 72.2%（26/36）. The defects of the previous operation included: stenosis of external auditory meatus（65/92, 70.7%）, obstruction of Eustachian tube（11/92, 12.0%）, and tympanitis（2/92, 2.2%）. Residual or recurrent lesions were most common in mastoid process and tympanic sinus（50/92, 54.3%）, followed by attic cell and anterior cavity（44/92, 47.8%）, posterior tympanic cavity（29/92, 31.5%）, perilabyrinthine cells（13/92, 14.1%）, sinus meningeal angle（13/92, 14.1%）, cells behind the facial nerve（12/92, 13.0%）, Eustachian tube（10/92, 10.9%）, and hypotympanum（9/92, 9.8%）. Conclusion:The main causes of mastoid cavity infecion after mastoidectomy include incomplete removal of the lesion and inadequate drainage conditions. The key techniques of revisional mastoidectomy include disc-shaped operative cavity, skeletonization of mastoid process, reduction of facial nerve ridge, management of Eustachian tube and conchaplasty. The above techniques are also key in the first operation in order to improve the success rate of operation and avoid revision operation.

[Quality of life assessment after endoscopic and microscopic myringoplasty using Chinese version of the Zurich chronic middle ear inventory].

Objective:To assess and compare therapeutic effects and quality of life after endoscopic and microscopic myringoplasty using Chinese version of the Zurich chronic middle ear inventory（ZCMEI）. Methods:Patients with chronic suppurative otitis media underwent myringoplasty at the Third Hospital of Peking University from October 2018 to September 2019 were included in this study and divided into two groups: endoscopic tympanoplasty group（n=40） and microscopic tympanoplasty group（n=57）. ZCMEI survey and pure tone audiometry were conducted preoperatively and 3-9 months postoperatively. The operation time, intraoperative blood loss, length of hospital, graft success rate, complication rate, hearing improvement and quality of life improvement were compared. Results:①The operation time, length of hospital and intraoperative blood loss of endoscopic group were significantly lower（P<0.05）. ②The graft success rate was 92.5% and 98.2%, respectively（P>0.05）. The difference between the complication rate in two groups was not significant, but patients in endoscopic group had no symptoms of wound numbness or pain. ③Air conduction threshold（AC） and air-bone gap（ABG） were significantly lower after surgery in endoscopic group（n=33） and microscopic group（n=43）. The analyzed result of generalized linear model indicated surgical approach had no influence on postoperative AC and ABG（P>0.05）. ④The total scores of ZCMEI were significantly improved in endoscopic group（n=32） and microscopic group（n=48） postoperatively, as well as the scores of ear symptoms, hearing and psychosocial impact（P<0.05）. Preoperative and postoperative scores of medical resources were not significantly different in either groups（P>0.05）. Controlling the course of disease, the total ZCMEI results and scores of each subscale in patients with single ear involved（n=71） had no significant difference between two groups. Conclusion:Endoscopic myringoplasty has the advantages of minimal invasiveness, short operation time, and quick recovery evaluated from subjective and objective aspects. Audiometry improvement, graft success rate, complication rate and quality of life improvements are comparable between endoscopic tympanoplasty and conventional microscopic tympanoplasty. The assessment of the quality of life is of great significance in efficacy evaluation of otitis media. Doctors should comprehensively consider patient's subjective experience and the objective improvement to obtain the best clinical efficacy.

[Clinical analysis of 21 cases of cholesteatoma recidivism after canal-wall-up mastoidectomy with tympanoplasty].

Objective:To discuss the possible reasons for cholesteatoma recidivism after canal-wall-up mastoidectomy with tympanoplasty by analyzing clinical characteristics of patients. Methods:Data of 21 cases who suffered from cholesteatoma recidivism after canal-wall-up surgery were retrospectively reviewed, including preoperative examination, high resolution temporal bone CT, and intraoperative findings. Results:90.5%（19/21） cases had recurrent cholesteatoma with retraction pockets. Among 12 cases with previous operative notes, 66.7%（8/12） had extensive cholesteatoma which was not limited to attic in the original surgery. The intraoperative features of revision surgery in 21 patients including the destruction of reconstructive lateral attic wall and scutumwere found in 19.0%（4/21） cases, the head of malleus left in 19.0%（4/21） cases, the cholesteatoma found in hidden part in 14.3%（3/21） cases, the hadeustachian tube dysfunction in 38.1%（8/21）cases. the sclerotic mastoid in 42.9%（9/21） cases. hadanatomic variations of the temporal bone in 14.3%（3/21） cases and atresia of external auditory canal in 4.8%（1/21） cases. Conclusion:In this group of recidivism cases, most patients had extensive cholesteatoma, which may lead to excessive mucosa loss during lesion clearance, poor ventilation of tympanic isthmus after surgery, and promote the formation of retraction pocket. In addition, some cases had eustachian tube dysfunction, unstable reconstruction of attic lateral wall, and improper selection of the indications, which may also increase the risk of recurrence. Therefore, in order to reduce cholesteatoma recidivism after canal-wall-up surgery, attention should be paid to the striction of surgical indications, comprehensive preoperative evaluation, thorough clearance of lesions and firm reconstruction.

Label-Free Resistance Cytometry at the Orifice of a Nanopipette.

Development of new principles and techniques at the single-cell level is significantly important since cells as basic units of living organisms always bear large heterogeneity. Herein, we demonstrate a new electrochemical principle for single-cell analysis based on an ion current blockage at the orifice of a nanopipette, defined as resistance cytometry. The amplitude and the frequency of ion current transients show strong dependence on the size and the concentration of cells, which could be used for in situ cell sizing and counting. This technique shows good ability to detect the size change of RBCs under stimulations of different pH and osmotic pressure values. More importantly, the as-presented resistance cytometry can distinguish lymphoma blood cells from normal blood cells for patient blood samples. The as-presented resistance cytometry is label-free, non-invasive, and non-destructive, which not only opens new opportunities for single-cell analysis but also provides a new platform for cell-related medical diagnostic technologies.

[Application of 3D U-net in automatic segmentation of middle ear surgery structures in temporal bone CT].

Objective:To study the feasibility of fully automatic segmentation of labyrinth, facial nerve and ossicles in clinical routine temporal bone CT images based on 3D U-net neural network. Method:Clinical data were divided into two groups: ①Normal group: data were randomly assigned from 30 patients for routine temporal bone CT examination; ②Abnormal group: cochlear, ossicles and facial nerve morphology variation of 1 case each. The structures of facial nerve, labyrinth and ossicles were manually initial segmented and fine segmented by 2 clinicians with Mimics 20.0. Three-dimensional convolutional neural network（3D U-Net） was selected to conduct deep learning on the same data. The dice similarity coefficient（DSC） was used as the evaluation index. Result:The 3D U-net neural network was used to automatically segment the labyrinth, ossicles and facial nerve in the routine temporal bone CT. In the normal group, the DSC of labyrinth, ossicles and facial nerve were 0.79±0.03, 0.64±0.05 and 0.49±0.09, respectively. In the abnormal group, the DSC of these structures were 0.71, 0.54 and 0.40. Conclusion:According to the anatomical characteristics of the temporal bone, the labyrinth, ossicles and the facial nerve can be totally automatic segmented by 3D U-net neural network, and the accuracy was closed to that of manual segmentation. This method is feasible, fast and accurate.

[The physiological function of cingulate cortex and its role in the mechanism of tinnitus].

Cingulate cortex, as an important part of limbic system, is connected with number of areas in the brain, which regulate and control the conduction of multiple sensations. Studies of tinnitus have shown that abnormal changes in cingulate cortex are involved in the process of tinnitus, and play a key role in noise cancelling, cognition and emotional experience of tinnitus. This paper reviews the physiological function of the cingulate cortex and its role in the mechanism of tinnitus, providing new ideas for the treatment of tinnitus.

Image-guided cochlear access by non-invasive registration: a cadaveric feasibility study.

Image-guided cochlear implant surgery is expected to reduce volume of mastoidectomy, accelerate recovery, and improve safety. The purpose of this study was to investigate the safety and effectiveness of image-guided cochlear implant surgery by a non-invasive registration method, in a cadaveric study. We developed a visual positioning frame that can utilize the maxillary dentition as a registration tool and completed the tunnels experiment on 5 cadaver specimens (8 cases in total). The accuracy of the entry point and the target point were 0.471 ± 0.276 mm and 0.671 ± 0.268 mm, respectively. The shortest distance from the margin of the tunnel to the facial nerve and the ossicular chain were 0.790 ± 0.709 mm and 1.960 ± 0.630 mm, respectively. All facial nerves, tympanic membranes, and ossicular chains were completely preserved. Using this approach, high accuracy was achieved in this preliminary study, suggesting that the non-invasive registration method can meet the accuracy requirements for cochlear implant surgery. Based on the above accuracy, we speculate that our method can also be applied to neurosurgery, orbitofacial surgery, lateral skull base surgery, and anterior skull base surgery with satisfactory accuracy.