Selection of a Surgical Approach for Middle Ear Cholesteatoma Based on the Fusion Images of Non-Echo Planar Diffusion-Weighted MRI and CT.

PURPOSE: This study aimed to explore the ability of fusion images of non-echo planar diffusion-weighted magnetic resonance imaging (non-EPI-DWI MRI) and computed tomography (CT) to accurately locate cholesteatoma and plan the surgical approach. METHODS: In the first part, 41 patients were included. Their CT images and non-EPI DWMRI images were fused. The scope of cholesteatoma in the fusion image was compared with that in the surgical video to evaluate the capability to locate cholesteatoma. A total of 229 patients were included in the second part, and they were divided into 2 groups. We chose the surgical approach for the CT group and the fusion group, and compared the accuracy of surgical approaches in the CT group and the fusion group using the surgical records. RESULTS: The location of cholesteatoma shown in the fusion images was almost identical to that observed during the operation (kappa = .862). The overall specificity and sensitivity of the fusion images in locating cholesteatoma were 94.12% and 93.06%, respectively. The accuracy of surgical approach selection based on the fusion images (99.02%) was higher than that of surgical approach selection based on the CT images (85.83%). CONCLUSION: It is recommended that the fusion images be used to locate the range of the cholesteatoma before operation.

Otomastoiditis Caused by Nocardia Farcinica: A Case Report and Literature Review.

Nocardia farcinica usually infects people with impaired immune status and usually manifests in the lungs. Otomastoiditis caused by Nocardia infection is extremely rare, with only 4 cases reported to date. This report describes a case of otomastoid N. farcinica infection in an immunocompetent patient. The case was a 10-month-old immunocompetent infant who presented with an approximately 3-month history of right ear discharge for which treatment with various antibiotics had not resulted in significant improvement. Multiple cultures of secretions and pathologic examination failed to identify the causative organism. The patient then underwent right mastoidectomy. Finally, metagenomic next-generation sequencing identified the pathogen to be N. farcinica. The patient was infection-free at the 6-month follow-up but had developed labyrinthitis ossificans. Otomastoid Nocardia infection has characteristic clinical features, namely, formation of a large amount of granulation tissue and coexistence of bone destruction and new bone formation. Traditionally, Nocardia is challenging to diagnose. Metagenomic next-generation sequencing of lesions is helpful. Complete local debridement and free drainage are key to treatment.

Effects of CIK Cell Therapy Combined with Camrelizumab on the Quality of Life in Patients with Nasopharyngeal Carcinoma and Analysis of Prognostic Factors.

Objective: To investigate the effects of CIK (cytokine-induced killer) cell therapy combined with camrelizumab on the quality of life in patients with nasopharyngeal carcinoma and prognostic factors. Methods: In this retrospective study, the materials of 80 patients with nasopharyngeal carcinoma treated in our hospital (February 2017-February 2019) were retrospectively analyzed, and they were equalized into experimental group (n = 40) and control group (n = 40) according to the order of admission. Both groups received 200 mg of camrelizumab on day 1 combined with 10 mg of anrotinib from day 2 to day 4. The patients received the above program every 3 weeks and 4 treatment cycles. The experimental group also received CIK cell therapy simultaneously. The patients' quality of life, immune indexes, local control, metastasis, and survival rate were compared between the two groups, and the prognostic factors were analyzed by logistic analysis. Results: Compared with the control group, the experimental group achieved much higher scores of physical well-being (18.38 ± 2.31), social/family well-being (16.40 ± 2.24), emotional well-being (15.35 ± 2.30), functional well-being (17.30 ± 2.20), and head and neck cancer subscale (15.40 ± 2.01, P < 0.001) and eminently better immune indexes (P < 0.001) after treatment. During the 24-month follow-up, there were 2 recurrent cases (5.0%) and 2 cases (5.0%) with distant metastasis among the 40 patients in the experimental group; there were 8 recurrent cases (20.0%) and 7 cases (17.5%) with distant metastasis among the 40 patients in the control group. In the experimental group, the median survival period was 18 months and the 2-year survival rate was 97.5% (39/40). In the control group, the median survival period was 14 months and the 2-year survival rate was 85.0% (34/40). Among the 80 patients, 7 cases (8.75%) died and 73 cases (91.25%) survived. After conducting the single-factor analysis, remarkable differences in the cases of IV stage, quality of life after treatment, and immune indexes after treatment between the survival group and the death group were observed (P < 0.05). According to the multiple-factor analysis, the clinical stage and immune indexes were identified as the prognostic factors. Conclusion: CIK cell therapy combined with camrelizumab can enhance the life quality and immune function of the patients with nasopharyngeal carcinoma, thus improving their prognoses.

Hydroxytyrosol enhances cisplatin-induced ototoxicity: Possible relation to the alteration in the activity of JNK and AIF pathways.

Hydroxytyrosol (HT), a polyphenol widely contained as an ester in olive fruits and olive leaves, exhibits a broad spectrum of effectiveness. The present study was designed to investigate the effect of HT alone as well as in the combination with cisplatin on the House Ear Institute-Organ of Corti 1 cells (HEI-OC1) and C57BL/6 cochlear hair cells in vitro. The cell viability was measured by cell counting kit-8 (CCK8) assay. The levels of reactive oxygen species were evaluated by Dichloro-dihydro-fluorescein diacetate (DCFH-DA) staining. The expression of phosphorylated Jun N-terminal kinase (p-JNK) and cleaved-caspase 3 was assessed by Western blotting. The apoptosis was detected by terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) staining. The distribution of apoptosis inducing factor (AIF) was determined by immunofluorescent staining. HT alleviated the levels of reactive oxygen species in both untreated state and after cisplatin stimulus. However, HT at concentration of 100 µM decreased the cell viability of HEI-OC1 from 100 ± 17.38% in control group to 50.17 ± 1.89% and increased the expression of p-JNK and c-caspase 3 from 0.62 ± 0.10, 0.20 ± 0.050 in the control group to 1.24 ± 0.18, 0.85 ± 0.18 in the group treated with 30 µM cisplatin, as well as to 1.64 ± 0.14, 1.44 ± 0.12 in the group with 30 µM cisplatin +100 µM HT, respectively. Meanwhile, HT triggered AIF transferring to nuclei and, also, led to cochlear HCs arranging disorderly and missing. Moreover, HT elevated the expression of p-JNK and c-caspase 3 from 1.00 ± 0.27, 1.00 ± 0.26 in the control group to 2.23 ± 0.24, 22.87 ± 3.80 in the group with 30 µM cisplatin, and to 2.75 ± 0.23, 31.56 ± 3.86 in the group with 30 µM cisplatin+100 µM HT correspondingly. Taken together, data from this work reveal that HT itself possesses toxic effect on HCs mainly thorough AIF-dependent apoptosis, while, it aggravates the ototoxicity-caused by cisplatin via both JNK and AIF pathways related apoptosis. Findings from this work offer clear evidence that that HT might not be recommended to utilize for preventing cisplatin-induced ototoxicity.

Paeoniflorin protects spiral ganglion neurons from cisplatin-induced ototoxicity: Possible relation to PINK1/BAD pathway.

The objective of this study was to elucidate whether paeoniflorin (PF) exerted an effect on cisplatin-induced spiral ganglion neuron (SGN) damage, with special attention given to the role of PINK1/BAD pathway in this process. Middle cochlear turn culture and C57BL/6 mice were utilized to identify the character of PF in vitro and in vivo. We found that cisplatin treatment led to SGN damage, in which reactive oxygen species (ROS) generation increased, PINK1 expression decreased, BAD accumulation on mitochondria raised and mitochondrial apoptotic pathway activated. Conversely, we demonstrated that PF pre-treatment obviously mitigated cisplatin-induced SGN damage. Mechanistic studies showed that PF could reduce ROS levels, increase PINK1 expression, decrease the BAD accumulation on mitochondria and, thus, alleviate the activated mitochondrial apoptosis in SGNs caused by cisplatin. Overall, the findings from this work reveal the important role of PF and provide another strategy against cisplatin-induced ototoxicity.

PINK1 Protects Against Gentamicin-Induced Sensory Hair Cell Damage: Possible Relation to Induction of Autophagy and Inhibition of p53 Signal Pathway.

Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) is a gatekeeper of mitochondrial quality control. The present study was aimed to examine whether PINK1 possesses a protective function against gentamicin (GM)-induced sensory hair cell (HC) damage in vitro. The formation of parkin particles (a marker revealing the activation of PINK1 pathway which is a substrate of PINK1 and could signal depolarized mitochondria for clearance) and autophagy were determined by immunofluorescence staining. The expressions of PINK1, LC3B, cleaved-caspase 3 and p53 were measured by Western blotting. The levels of reactive oxygen species (ROS) and apoptosis were respectively evaluated by DCFH-DA staining, Annexin V Apoptosis Detection Kit and TUNEL staining. Cell viability was tested by a CCK8 kit. We found that treatment of 400 µM GM elicited the formation of ROS, which, in turn, led to PINK1 degradation, parkin recruitment, autophagy formation, an increase of p53 and cleaved-caspase 3 in HEI-OC1 cells and murine HCs. In contrast, co-treatment with ROS scavenger N-acetyl-L-cysteine (NAC) inhibited parkin recruitment, alleviated autophagy and p53 pathway-related damaged-cell elimination. Moreover, PINK1 interference contributed to a decrease of autophagy but an increase of p53 level in HEI-OC1 cells in response to GM stimulus. Findings from this work indicate that PINK1 alleviates the GM-elicited ototoxicity via induction of autophagy and resistance the increase of p53 in HCs.

Activation of NLRX1-mediated autophagy accelerates the ototoxic potential of cisplatin in auditory cells.

To date, the mechanism (s) underlying the cisplatin-elicited ototoxicity has not been elucidated fully. Nucleotide-binding domain and leucine-rich-repeat-containing family member ×1 (NLRX1), a cytoplasmic pattern recognition receptor, is tightly related to mitochondrial function, reactive oxygen species (ROS) production, and autophagy. In this work, autophagy alteration, NLRX1 expression, ROS generation and cell injury were investigated correspondingly by immunofluorescence staining, western-blot, TEM, flow cytometry and MTT in HEI-OC1 cells of both NLRX1 overexpression and silencing in response to cisplatin stimulus. We found that NLRX1 expression was increased concurrent with the increase of autophagy activation in HEI-OC1 cells under the cisplatin insult. NLRX1 overexpression led to the amount of accumulation of autophagsomes in HEI-OC1 cells in normal condition and a higher activation of autophagy concurrent with cell injury in HEI-OC1 cells treated with cisplatin, whereas, NLRX1 silencing decreased the activation level of autophagy concurrent with increased cell viability in HEI-OC1 cells treated with cisplatin. Mechanistic studies showed that NLRX1 potentiated mitochondrial-derived ROS generation in response to cisplatin exposure. Inhibition of ROS generation significantly prevented autophagy activation and apoptosis both in HEI-OC1cells and cochlear explants treated with cisplatin. The findings from this work reveal that NLRX1 sensitizes auditory cells in vitro to cisplatin-induced ototoxity via autophagic cell death pathway, providing another strategy against cisplatin-induced ototoxity.

[Mutation analysis of 16 mutation spots related to children patients with non-syndromic sensorineural hearing loss].

OBJECTIVE: To explore the clinical signification of screening 16 target deafness mutations in GJB2, GJB3, SLC26A4, WFS1 and mitochondrial DNA 12S rRNA in 135 children patients with non-syndromic sensorineural hearing loss (NSHL) in Zibo City, Shandong province. METHOD: Peripheral blood samples of 135 subjects in the study diagnosed as NSHL were collected; Polymerase chain reaction (PCR) and direct sequencing were used to analyze the 16 mutation spots. RESULT: Sixty-two cases of 135 patients (45.9%, 62/135) were found out to be carries of at least one pathogenic gene mutation. Among them, 24 cases (17.8%, 24/135) had two mutated alleles (homozygote and compound heterozygote), and 38 cases (28.1%, 38/135) were single mutant carriers. Among all the children patients, 30 cases (22. 2%, 30/135) had SLC26A4 mutations, and 19 cases (14.1%, 19/135) had GJB2 mutations. In the study 86 Mutant alleles were detected, and the allele frequency of SLC26A4 c. 766_2A > G and GJB2 c. 235delC was 11.11% (30/270) and 8.5% (23/270) respectively. The allele frequency of SLC26A4 c. 2168A > G and WFS1 c. 2158A > G is 2.6% (7/270). CONCLUSION: SLC26A4 mutation is the primary cause of the patients with NSHL in this study, and GJB2 mutation is the secondary. The most common mutant form is c. 766_2A of SLC26A4, and the second is c. 235delC of GJB2. GJB3 and WFS1 mutations were detected, whereas mtDNA mutations were not found out in this study.

[Diagnosis and therapy for horizontal semicircular canal cupulolithiasis].

OBJECTIVE: By analysing the video-nystagmography findings of positional tests,to evaluate the therapeutic effect of the patients with horikontal semicircular canal cupulolithiasis (HSC-Cup). METHOD: A retrospective study of 36 patients with HSC-Cup. The induced nystagmus in roll tests was recorded by videonystagmography, whose direction, latency, intensity and time characteristics were analysed. All of the 36 patients were treated with lying position avoiding normal side and oral-taken betahistine mesilate tablets. A week later return visits and curative effects evaluation were made. RESULT: Horizontal apogeotropic nystagmus was induced by turning left or right in HSC-Cup roll tests. The time of latency and duration turning to normal and lesion side were(0. 93 ± 0. 65)s and(1. 01 ± 0. 78)s, (100.58 ± 36. 56)s and (118. 65 ± 143. 71)s, which showed no statistically significant difference (P>0. 05). The duration of nystagmus was more than 60 seconds. The intensity of nystagmus turning to normal and lesion side were(45.58 ± 28.71)°/s and (20.42 ± 16. 64)°/s. The intensity turning to normal side was greater than lesion side obviously. The difference was statistically significant (P<0. 05). Twenty-three patients withright HSC-Cup, and 13 patients with left HSC-Cup were taken in count. They were treated with above methods and return visit a week later. Twenty-eight patients (77. 77%) were cured, 36 patients (100. 00%) were improved. There were 4 patients recurrence during the follow-up. CONCLUSION: The direction and duration time of induced nystagmus are available to diagnose the HSC-Cup. The lesion side may determined according to the intensity of induced nystagmus. Lying position avoiding normal side and oral-taken betahistine mesilate tablets is an effective treatment methods for HSC-Cup.

[Application research of polysomnography and lateral cephalometric radiographs in the diagnosis and treatment of sleep-disordered breathing in children].

OBJECTIVE: To explore the application of polysomnography (PSG) and lateral cephalometric radiographs (LCR) in the diagnosis and treatment of sleep-disordered breathing (SDB) in children. METHOD: To select 157 cases of children suffering from SDB, 115 cases with primary snoring (PS) and 42 cases with obstructive sleep apnea hypopnea syndrome (OSAHS). After bilateral tonsillectomy and adenoidectomy, preoperative and postoperative LCR and PSG of measure were observed for statistical analysis. RESULT: Compared the group PS and group OSAHS; the thickness of adenoids was significantly different(P<0. 01). The preoperative oblique diameter of nasopharyngeal airway was significantly different (P<0. 05). There were significant differences on the preoperative and postoperative nasopharyngeal airway oblique diameter and oropharyngeal airway anteroposterior diameter in group PS and group OSAHS (all, P<0. 01). There were significant differences on the preoperative and postoperative AHI and LSaO2 in the group OSAHS (both, P<0. 01). The total effective rate of group PS was 97. 4% (112/115), and the total effective rate of group OSAHS was 97. 6% (41/42). CONCLUSION: PSG and LCR have a very important role in the diagnosis and treatment of SDB in children. Bilateral tonsillectomy and adenoidectomy are the primary means of treatment in children with SDB.

[Objective evaluation of CO2 laser in the treatment of Tis--T glottic carcinoma after operation for voice rehabilitation].

OBJECTIVE: To objectively evaluate the voice rehabilitation status in different period after treatment of Tis--T1 glottic carcinoma by CO2 laser with voice parameters. METHOD: A retrospective review of 41 cases with Tis--T1 glottic carcinoma treated by CO2 laser was performed, 23 cases were stage Tis (Tis group) and 18 cases with stage T1N0M0 (T1 group). The range of excision of the lesion by CO2 laser was according to the different stages of the tumor, and ensured theoperation negative margin was by intraoperative frozen pathological examination. We tested and compared the actual voice (coritaine F0, Jitter, Shimmer, NNE and MPT) of 30 cases of healthy middle-aged and old male(normal group) and all the patients at one day prior to operation, three months, six months and one year after operation respectively, which was to evaluate the voice rehabilitation status in different period after operation objectively. RESULT: Postoperative pathological examination revealed, 23 cases were squamous epithelium severe atypical hyperplasia, 16 cases were well differentiated squamous cell carcinoma, and 2 cases were moderately differentiated squamous cell carcinoma. Palatoglossal arch mucosal tear occurred in 3 patients. Respiratory difficulties were not seen in all cases, and normal oral feeding was obtained in all cases in postoperative three days. All patients were followed up for one year. There was statistical significance in F0, Jitter, Shimmer of both Tis group and T1 group after operation in different periods(P<0.05). But there was no statistical significance in NNE and MPT between six months and one years after operation in the two groups(P>0.05). CONCLUSION: CO2 laser surgery is an effective treatment for early glottic carcinoma. Postoperative vocal function was improved in varying degrees, and voice quality gradually improved with the rehabilitation time. Partly objective parameters reflecting the vocal function gradually stabilized after half a year after operation.