Treatment of congenital middle ear cholesteatoma in children using endoscopic and microscopic ear surgeries: a case series.

Introduction: Surgical removal is widely employed in children with congenital middle ear cholesteatoma (CMEC). Here, we report the surgical outcomes of CMEC removal via endoscopic ear surgery (EES) and microscopic ear surgery (MES) in children. Methods: Children with CMEC who underwent preoperative medical history inquiry, hearing test, endoscopic evaluation, and radiology imaging before receiving EES or MES were included. Postoperative audiological outcomes and recurrence rates were collected. Results: Seventeen children (20 ears) with stage II-IV CMEC were included. Of those, 11 ears (55.0%) underwent EES, and 9 ears (45.0%) underwent MES. The follow-up time was 35 ± 13.5 months. One child in the EES group with stage III CMEC had a recurrence during the follow-up period. In the EES group, the average minimum diameter of the external auditory canal on the affected side was 5.8 mm (4.3-8.0 mm). No linear association was found between age and the minimum diameter of the external auditory canal. Discussion: EES is a promising treatment option for children with early-stage CMEC because of its low recurrence rate and minimally invasive nature. The minimum diameter of the external auditory canal on the affected side should be meticulously examined when performing EES in children.

[Postoperative effect analysis of different surgical techniques used in facial nerve reconstruction].

Objective:To investigate the factors and efficacy of different surgical techniques used in facial nerve（FN） reconstruction. Methods:A retrospective analysis was conducted on 24 patients who underwent facial nerve reconstruction surgery in our department from January 2016 to January 2021. The duration of total facial nerve paralysis was less than 18 months. The study included 5 surgical techniques, including 6 cases of FN anastomosis（Group A）, 5 cases of FN grafting（sural nerve or great auricular nerve）（Group B）, 5 cases of side-to-end facial-hypoglossal nerve anastomosis（Group C）, 4 cases of side-to-end FN grafting（sural nerve or great auricular nerve） hypoglossal nerve anastomosis（Group D）, and 4 cases of dual nerve reanimation（Group E）. The postoperative follow-up period was ≥1 year. Results:The HB-Ⅲ level of FN function at 1 year after surgery was 83.3%（5/6） in group A, 60.0%（3/5） in group B, 40.0%（2/5） in group C, 25.0%（1/4） in group D, and 50.0%（2/4） in group E. In patients without multiple FN repair, the incidence of synkinesis was 15.0%（3/20）, while no cases of synkinesis were observed in patients with dual nerve reanimation. The patients who underwent hypoglossal-facial side-to-end anastomosis showed no hypoglossal nerve dysfunction. Conclusion:Different FN repair techniques result in varying postoperative FN function recovery, as personalized repair should be managed. Among the various techniques, FN end-to-end anastomosis after FN transposition is recommended as to reduce the number of anastomotic stoma, while hypoglossal-facial side-to-end anastomosis is advocated as to prevent postoperative hypoglossal nerve dysfunction. Additionally, dual nerve repair can effectively improve smile symmetry and reduce synkinesis, which enhances patients' quality.

Oligodendrocyte Progenitor Cell Transplantation Ameliorates Preterm Infant Cerebral White Matter Injury in Rats Model.

Background: Cerebral white matter injury (WMI) is the most common brain injury in preterm infants, leading to motor and developmental deficits often accompanied by cognitive impairment. However, there is no effective treatment. One promising approach for treating preterm WMI is cell replacement therapy, in which lost cells can be replaced by exogenous oligodendrocyte progenitor cells (OPCs). Methods: This study developed a method to differentiate human neural stem cells (hNSCs) into human OPCs (hOPCs). The preterm WMI animal model was established in rats on postnatal day 3, and OLIG2+/NG2+/PDGFRα+/O4+ hOPCs were enriched and transplanted into the corpus callosum on postnatal day 10. Then, histological analysis and electron microscopy were used to detect lesion structure; behavioral assays were performed to detect cognitive function. Results: Transplanted hOPCs survived and migrated throughout the major white matter tracts. Morphological differentiation of transplanted hOPCs was observed. Histological analysis revealed structural repair of lesioned areas. Re-myelination of the axons in the corpus callosum was confirmed by electron microscopy. The Morris water maze test revealed cognitive function recovery. Conclusion: Our study showed that exogenous hOPCs could differentiate into CC1+ OLS in the brain of WMI rats, improving their cognitive functions.

Differentiation of geniculate ganglion venous malformation from schwannoma: dynamic T1-weighted imaging provides unique diagnostic value.

OBJECTIVE: To distinguish geniculate ganglion venous malformation (GGVM) from schwannoma (GGS) by using high-resolution CT (HRCT), routine MRI, and dynamic T1-weighted imaging (T1WI) characteristics. METHODS: Surgically confirmed GGVMs and GGSs between 2016 and 2021 were retrospectively included. Preoperative HRCT, routine MR, and dynamic T1WI were performed on all patients. Clinical data, imaging characteristics including lesion size, involvement of facial nerve (FN), signal intensity, enhancement pattern on dynamic T1WI, and bone destruction on HRCT were evaluated. Logistic regression model was developed to identify independent factors for GGVMs, and the diagnostic performance was accessed by receiving operative curve (ROC) analysis. Histological characteristics were explored for both GGVMs and GGSs. RESULTS: Twenty GGVMs and 23 GGSs with mean age of 31 were included. On dynamic T1WI, 18 GGVMs (18/20) showed "pattern A" enhancement (a progressive filling enhancement), while all 23 GGSs showed "pattern B" enhancement (a gradual whole-lesion enhancement) (p < 0.001). Thirteen GGVMs (13/20) showed the "honeycomb" sign whereas all GGS (23/23) showed extensive bone changes on HRCT (p < 0.001). Lesion size, involvement of FN segment, signal intensity on non-contrast T1WI and T2-weighted imaging (T2WI), and homogeneity on enhanced T1WI were obviously differed between two lesions (p < 0.001, p = 0.002, p < 0.001, p = 0.01, p = 0.02, respectively). Regression model showed the "honeycomb" sign and "pattern A" enhancement were independent risk factors. Histologically, GGVM was characterized by interwoven dilated and tortuous veins, while GGS was characterized by abundant spindle cells with dense arterioles or capillaries. CONCLUSIONS: The "honeycomb" sign on HRCT and "pattern A" enhancement on dynamic T1WI are the most promising imaging characteristics for differentiating GGVM from GGS. CLINICAL RELEVANCE STATEMENT: The characteristic sign and enhancement pattern on HRCT and dynamic T1-weighted imaging allow preoperative differentiation of geniculate ganglion venous malformation and schwannoma feasible, which will improve clinical management and benefit patient prognosis. KEY POINTS: • The "honeycomb" sign on HRCT is a reliable finding to differentiate GGVM from GGS. • GGVM typically shows "pattern A" enhancement (focal enhancement of the tumor on early dynamic T1WI, followed by progressive contrast filling of the tumor in the delayed phase), while "pattern B" enhancement (gradual heterogeneous or homogeneous enhancement of the whole lesion) is observed in GGS on dynamic T1WI.

Indications of and Efficacy of Facial Nerve Decompression Through Endoscopic Transcanal Approach for Patients with Traumatic Facial Paralysis.

BACKGROUND: The aim of this study is to evaluate the indications and efficacy of facial nerve decompression through an endoscopic transcanal approach for patients with traumatic facial paralysis. METHODS: This single-center retrospective study included 11 patients with traumatic facial paralysis from February 2018 to April 2019. We compared the facial nerve and auditory function before and after operation so as to reveal the feasibility and effect of the surgical approach. RESULTS: All 11 patients have successfully received facial nerve decompression through endoscopic transcanal approach. Facial nerve function was objectively evaluated by electroneurography test and House-Brackmann facial nerve grading system. All patients were graded HB-VI with electroneurography ≥ 95% before surgery. The recovery of facial nerve function was good (HB-I or II) (90.9%) a year after surgery with only one case (9.1%) for HB-III. Preoperative high-resolution computed tomography showed that 1 patient had ossicular chain interruption, which was confirmed during operation. Meanwhile, 2 patients with air-bone gap >35 dBHL and whose computed tomography failed to diagnose were found with ossicular chain interruption during operation. The air-bone gap of patients with normal ossicular chain connection was all <30 dBHL. The average air-bone gap was reduced from 27.5 ± 10.1 dBHL to 7.8 ± 3.3 dBHL after operation. CONCLUSION: Preoperative high-resolution computed tomography combined with localization test can accurately estimate the location of facial nerve injury. Facial nerve decompression through endoscopic transcanal approach can decompress the geniculate ganglion to pyramidal segment of facial nerve, which is suitable for patients with traumatic facial paralysis of this segment. In addition, air-bone gap >35 dBHL may indicate the ossicular chain interruption when it is difficult to be completely judged by high-resolution computed tomography.

Identifying a novel frameshift pathogenic variant in a Chinese family with neurofibromatosis type 1 and review of literature.

AIM: To detect the pathogenic gene variant in a family with neurofibromatosis type 1 (NF1). METHODS: This patient with NF1 was sequenced using target sequence capture and high-throughput sequencing technology. After detecting the suspicious pathogenic variant type, the pathogenic variant sites of the patient and the patient's family members were verified by multiple ligation dependent probe amplification and Sanger sequencing. Sift, polyphen-2, Mutation Taster and GERP++ software were used to predict the pathogenicity of the unknown loci. The clinical data, diagnosis and treatment process of the patients were reviewed. Using the keyword "NF1; frameshift pathogenic variant", relevant literature was gathered for analysis from Chinese and international databases, with articles dating from the establishment of each database to April 2022. RESULTS: A heterozygous frameshift pathogenic variant of NF1 in exon 33 was detected in the patient. The insertion of adenine in coding region 4486 resulted in the replacement of isoleucine with asparagine in protein 1497. Sanger sequencing validation and segregation analysis were performed, which demonstrated that the NF1 gene was cosegregated with the disease phenotype in this family. This study identified a novel NF1 heterozygous frameshift mutation c.4486dupA (p.I1497Nfs*12). Relevant literature retrieval found 7 Chinese articles and 12 foreign articles. With NF1 gene mutation, mutation types are diverse, including point mutation, frameshift mutation, splice site mutation, exon mutation, chimeric mutation and de novo mutation. Foreign reports are based on autosomal dominant inheritance. CONCLUSION: This study's results demonstrate that a novel deletion in exon 33 caused NF1 in this Chinese family, expanding the mutational spectrum of the NF1 gene.

Simultaneous Bilateral Cochlear Implantation in Very Young Children Improves Adaptability and Social Skills: A Prospective Cohort Study.

OBJECTIVES: To investigate the value of using the Gesell Development Diagnosis Scale (GDDS) to predict developmental outcomes in very young children who undergo simultaneous bilateral cochlear implantation. DESIGN: In this prospective cohort study, a repeated-measures investigation was conducted in a tertiary referral hospital. A total of 62 children receiving simultaneous bilateral cochlear implantations were enrolled from April 2017 to August 2018. They were divided into 2 groups depending on the operative age: "Infants" group (6 to 12 months, N = 38) or "Children" group (12 to 36 months, N = 24). Data on the surgical outcomes, auditory development, speech production, and developmental indicators were collected until 2 years after the initial fitting. The primary outcome measure was the GDDS, a neuropsychological development examination. Secondary outcomes included the following: complication rate, aided pure-tone average, Infant-Toddler Meaningful Auditory Integration Scale, Categories of Auditory Performance-II, Meaningful Use of Speech Scale, Speech Intelligibility Rating, and the LittlEARS Auditory Questionnaire. RESULTS: The mean ages at implantation in infants and children groups were 9.2 ± 1.17 and 16.6 ± 3.60 months, respectively. Significant differences were found in the social skills ( p = 0.001) and adaptability ( p = 0.031) domains of GDDS. The younger the age of bilateral cochlear implants surgery, the higher developmental quotient of language, social skills, and adaptability the child could achieve after 2 years. The complication rates in the infants and children groups were 0% versus 2.1% ( p = 0.57). There was no surgical complication in the infants group. In the children group, 1 case with enlarged vestibular aqueduct and Mondini malformation had a receiver-implant misplacement on the right side (2%, 1/48). In the two groups, auditory performance and speech production had improved similarly. In the infants group, social skills developmental quotient at baseline had a significant positive relationship with Meaningful Use of Speech Scale after 2 years. CONCLUSIONS: Simultaneous bilateral cochlear implantation in younger children improves adaptability and social skills. GDDS is a sensitive tool of evaluating short-term effect of bilateral cochlear implants in neuropsychological development and constitutes a reliable predictor of speech production for the very younger pediatric cochlear implant users.

Optimization of an Intranasal Route for the Delivery of Human Neural Stem Cells to Treat a Neonatal Hypoxic-Ischemic Brain Injury Rat Model.

Objective: Stem cell administration via the intranasal route has shown promise as a new therapy for hypoxic-ischemic encephalopathy (HIE). In this study, we aimed to improve the intranasal delivery of stem cells to the brain. Methods: Human neural stem cells (hNSCs) were identified using immunofluorescence, morphological, and flow cytometry assays before transplantation, and cell migration capacity was examined using the transwell assay. Cerebral hypoxia-ischemia (HI) was induced in 7-day-old rats, followed by the intranasal transplantation of CM-Dil-labeled hNSCs. We examined various experimental conditions, including preconditioning hNSCs with hypoxia, catheter method, multiple low-dose transplantation, head position, cell appropriate concentration, and volume. Rats were sacrificed 1 or 3 days after the final intranasal administration, and parts of the nasal tissue and whole brain sections were analyzed under a fluorescence microscope. Results: The isolated hNSCs met the characteristics of neural stem cells. Hypoxia (5% O2, 24 h) enhanced the surface expression of CXC chemokine receptor 4 (CXCR4) (9.21 ± 1.9% ~ 24.76 ± 2.24%, P < 0.01) on hNSCs and improved migration (toward stromal cell-derived factor 1 [SDF-1], 0.54 ± 0.11% ~ 8.65 ± 1.76%, P < 0.001; toward fetal bovine serum, 8.36 ± 0.81% ~ 21.74 ± 0.85%, P < 0.0001). Further improvement increased the number of surviving cell distribution with increased uniformity on the olfactory epithelium and allowed the cells to stay in the nasal cavity for at least 72 h, but they did not survive for longer than 48 h. Optimization of pre-transplantation conditions augmented the success rate of intranasally delivered cells to the brain (0-41.6%). We also tentatively identified that hNSCs crossed the olfactory epithelium into the tissue space below the lamina propria, with cerebrospinal fluid entering the cribriform plate into the subarachnoid space, and then migrated toward injured areas along the brain blood vessels. Conclusion: This study offers some helpful advice and reference for addressing the problem of repeatability in the intranasal delivery of stem cells.

Single-Cell RNA Sequencing Reveals the Interaction of Injected ADSCs with Lung-Originated Cells in Mouse Pulmonary Fibrosis.

Pulmonary fibrosis (PF) is a severe chronic lung disease with little effective treatment options other than lung transplantation. Adipose-derived mesenchymal stem cells (ADSCs) have been shown to exert therapeutic effects on PF, but the underlying mechanisms remain to be further elucidated. Here, we show the interaction of ADSCs and lung-originated cells at the single-cell level, using bleomycin- (BLM-) induced mice PF model and green fluorescent protein- (GFP-) labeled mouse ADSCs. The intratracheally injected ADSCs were successfully recollected with flow cytometry and, together with lung-originated cells, were subjected to single-cell RNA sequencing (scRNA-seq). The ADSC treatment drastically changed the transcriptomic profile and composition of lung cells, especially macrophages. We explored the signal pathway interactions between ADSCs and lung-originated cells, showing potentially regulative pathways including NGR, ANNEXIN, HGF, and PERIOSTIN. Our data indicate that the injected ADSCs increased the number of Trem2 + antiinflammatory lung macrophages and lowered further inflammation and fibrosis in the lung. Our work realized the direct analysis of injected ADSCs to explore its in vivo interaction with the lung environment under PF and may provide critical information for future engineering of ADSCs to achieve better therapeutic effects in PF.

Synergistic Effect of Erastin Combined with Nutlin-3 on Vestibular Schwannoma Cells as p53 Modulates Erastin-Induced Ferroptosis Response.

Vestibular schwannoma (VS) is a rare neurotology neoplasm that results in partial neurological defects. As we know, a comprehensive understanding of basic mechanisms and targeted therapy is vital for disease management. In VS, p53 has been proved to suppress tumor progression via a cooperative with the key protein, merlin, as well as regulation of the cell cycle. However, there are more potential mechanisms of p53 in VS needed to exploit. First, via genome-wide RNA expression analysis, we identified differentially expressed genes in VS compared with normal nerves, and then, bioinformatics analyses were used to analyze these differential expression data and suggested a high level of enrichment of cysteine and glutathione metabolism pathways in VS. Meanwhile, we observed a downregulation of SLC7A11/xCT, a component of the cystine/glutamate antiporter (also known as system xc -) involved in cystine uptake. Next, for a deeper study, our group extracted tumor cells from vestibular schwannoma tissues and established two immortalized cell lines named JEI-001 and JEI-002. Secondly, in our established cells, we demonstrated that ferroptosis participated in erastin-induced growth inhibition. As a novel cell death process, ferroptosis driven by iron-mediated lipid reactive oxygen species (lipid ROS), as well as cysteine and glutathione metabolism. Furthermore, ferroptosis contributes to the inhibitory effects of tumor suppressor p53. Here, we show that p53 sensitizes schwannoma cells to ferroptosis by repressing expression of SLC7A11/xCT. Finally, erastin combined with Nutlin-3, which s to p53 activation, triggered antitumor effects of ferroptosis on the growth of schwannoma cells in vitro. These findings present potential mechanism of p53 in schwannomas and raise the possibility of treatment strategies directed against this pathogenesis.

Endoscopic transcanal facial nerve decompression in Bell's palsy: A pilot study.

PURPOSE: To explore the surgical effects of endoscopic facial nerve decompression in Bell's palsy. MATERIALS AND METHODS: This retrospective study included 15 patients with Bell's palsy. All had grade VI (House-Brackmann grading system) complete unilateral facial paralysis before surgery and a >95% reduction in amplitude on electroneurography testing compared to the unaffected side. Their MRI results indicated perineural edema in the geniculate ganglion area. Endoscopic decompression surgery was performed soon after they presented at our hospital. The time between onset of facial paralysis and surgery ranged from 25 to 93 days. All patients had no relevant surgical history or ear diseases. RESULTS: At 1-year follow-up, 13 of the 15 (87%) patients had recovered to normal or near-normal facial function (House-Brackmann grade I-II), and all patients had reached House-Brackmann grade III or lower facial function. No obvious air-bone gap or sensorineural hearing loss occurred after surgery, and there were no severe complications or synkinesis. CONCLUSIONS: Endoscopic transcanal facial nerve decompression provides a less traumatic and improved exposure of the geniculate ganglion, and may also help prevent permanent severe facial sequela. Results of intraoperative facial nerve stimulation may be related to the length of time required for recovery. The optimal time of surgery after onset of paralysis needs to be investigated further, to identify a post-drug surgical therapy which may be more acceptable for patients. Patients' response to conservative treatments should be assessed as soon as possible so as not to delay surgery.

Facial reanimation with interposition nerve graft or masseter nerve transfer: a comparative retrospective study.

Both interposition nerve grafts and masseter nerve transfers have been successfully used for facial reanimation after irreversible injuries to the cranial portion of the facial nerve. However, no comparative study of these two procedures has yet been reported. In this two-site, two-arm, retrospective case review study, 32 patients were included. Of these, 17 patients (eight men and nine women, mean age 42.1 years) underwent interposition nerve graft after tumor extirpation or trauma between 2003 and 2006 in the Ear Institute, School of Medicine, Shanghai Jiao Tong University, China, and 15 patients (six men and nine women, mean age 40.6 years) underwent masseter-to-facial nerve transfer after tumor extirpation or trauma between November 2010 and February 2016 in Shanghai Ninth People's Hospital, China. More patients achieved House-Brackmann III recovery after masseter nerve repair than interposition nerve graft repair (15/15 vs. 12/17). The mean oral commissure excursion ratio was also higher in patients who underwent masseter nerve transfer than in patients subjected to an interposition nerve graft. These findings suggest that masseter nerve transfer results in strong oral commissure excursion, avoiding obvious synkinesis, while an interposition nerve graft provides better resting symmetry. This study was approved by the Institutional Ethics Committee, Shanghai Ninth People's Hospital, China (approval No. SH9H-2019-T332-1) on December 12, 2019.

Origins of biallelic inactivation of NF2 in neurofibromatosis type 2.

BACKGROUND: Elucidating the mechanism by which biallelic inactivation evolved could provide a mechanistic understanding for NF2 tumorigenesis and also a rationale for clinical management. METHODS: A cohort of 60 NF2 patients was recruited. Next-generation sequencing of tumor and paired control samples was used to explore how NF2 mutations evolve in determining the clinical phenotypes. RESULTS: In total, 60 blood samples (one from each patient) and 61 (from 35 patients) NF2-associated tumors were collected. Next-generation sequencing of the blood samples detected "first hit" NF2 mutation in 35/60 donors (58.3%), 82.9% of which (29/35) bear heterozygous germline mutations, and 17.1% (6/35) of which are mosaics with variable allelic frequency (VAF). While a number of NF2 patients were found without germline mutation, most (57/61, 93.4%) NF2-associated tumors were identified with NF2 somatic mutation. We calculated the correlation between the onset latency of mosaic and germline NF2 allele carriers with the mosaicism VAF. The mosaicism VAF is negatively and linearly correlated to clinical symptom onset latency (R2 = 0.3677, P = .00351), suggesting biallelic inactivation probability is a linear function of "first hit" prevalence in the body. The second NF2 somatic mutation occurrence time positively correlates with the onset of clinical symptoms (R2 = 0.4151, P = .02633), suggesting tumor growth is linearly proportional to the time after biallelic inactivation. CONCLUSIONS: Our results suggested that biallelic inactivation of NF2 evolved through neutral drift and preexisting first hit NF2 allele determines certain aspects of the clinical symptoms. Genetic diagnosis should be included in the diagnostic criteria and treatment consideration of NF2.

Characterization of a newly established schwannoma cell line from a sporadic vestibular schwannoma patient.

A stable, human sporadic vestibular schwannoma cell line is not currently available. By using a lentivirus-mediated transfection from a 41-year-old sporadic vestibular schwannoma patient, primary schwannoma cells were obtained, cultured and immortalized using the hHERT gene. The NF2 gene of the resulting JEI-001 cell line contains a specific Exon 5 mutation. The schwannoma cell origin of this cell line was confirmed using STR techniques and immunocytochemistry. A comparison between the primary tumor tissue and JEI-001 revealed a common mutation of the NF2 gene, which indicated that the JEI-001 cell line had retained most of its original tumor characteristics. The JEI-001 cell line was found to be non-tumorigenic in nude mice, but certain growth features had been altered, resulting in changes such as independence from the Schwann cell growth factors and a higher proliferation rate. This was the first known study to establish cell lines immortalized from human sporadic vestibular schwannoma that had different characteristics from that of HEI-193. This is a novel model system that can be used for the study of NF2 gene functions, in order to elaborate on the biological features of sporadic vestibular schwannoma, even including familial NF2 tumors, and to further explore the molecular pathogenesis and develop new adjuvant therapies.

[Perioperative airway management of infantile subglottic hemangioma].

Objective:To investigate the relevant influencing factors for perioperative airway events of infantile subglottic hemangioma, and to further discuss the strategies of perioperative airway management. Methods:A total of 36 infants with subglottic hemangioma that had no response to the drug therapy and underwent surgical treatment from July 2007 to April 2017 were enrolled. The relevant influencing factors, including gender, age, birth weight, age of onset, degree of tracheal stenosis and histories of underlying diseases（congenital heart disease and respiratory disease）, were also recorded simultaneously. Intraoperative SpO2 decline, intraoperative emergency tracheal intubation, intraoperative emergency tracheotomy, whether preserving tracheal intubation after operation or not, and postoperative emergency tracheal intubation were included in the perioperative airway events of infantile subglottic hemangioma. The relevant influencing factors of perioperative airway events were analyzed so that meaningful statistical indicators were selected for grouped logistic regression analysis, and the correlation was evaluated based on OR value and 95% confidence interval（CI）. Based on the correlation between influencing factors and airway events, perioperative airway management was discussed. Results:①The degree of tracheal stenosis was a risk factor for SpO2 decline（95%CI[2.121-33.818]）; ②The degree of airway stenosis, history of comorbid cardiovascular disease and respiratory disease were the influencing factors for intraoperative emergency tracheal intubation（95%CI[0.863-21.692], [0-+∞] and [1.741-232.403], respectively）; ③The degree of airway stenosis was the influencing factor for postoperative emergency tracheal intubation（95%CI[1.277-20.421]）; ④The degree of airway stenosis was a risk factor for whether preserving postoperative tracheal intubation or not（95%CI[1.523-13.296]）. Conclusion:①Infants with a history of preoperative underlying diseases are more likely to present with intraoperative airway instability and SpO2 decline, which deserves more preoperative and postoperative attention. Tracheal intubation should be performed timely in case of intraoperative SpO2 decline. ②Preoperative tracheotomy should be performed in infants with preoperative grade Ⅲ airway stenosis, especially those with comorbid heart diseases or respiratory diseases. ③The degree of airway stenosis is an extremely important influencing factor for perioperative airway management of infantile subglottic hemangioma. For infants whose airway stenosis were greater than 60% of airway diameter, the airway maintenance should be closely monitored. Once SpO2 decreases, tracheal intubation should be performed immediately. It's recommended to preserve tracheal intubation so as to ensure the airway stability. The tracheal intubation could be prolonged to 48-72 hours postoperatively. ④The surgical approach has no significant effect on perioperative airway management.

High throughput proteomic and metabolic profiling identified target correction of metabolic abnormalities as a novel therapeutic approach in head and neck paraganglioma.

Head and neck paragangliomas (HNPGLs) are rare neoplasms that represent difficult treatment paradigms in neurotology. Germline mutations in genes encoding succinate dehydrogenase (SDH) are the cause of nearly all familial HNPGLs. However, the molecular mechanisms underlying tumorigenesis remain unclear. Mutational analysis identified 6 out of 14 HNPGLs harboring clinicopathologic SDH gene mutations. The SDHB gene was most frequently mutated in these patients, and western blot showed loss of SDHB protein in tumors with SDHB mutations. The paraganglioma cell line (PGL-626) was established from a sample that harbored a missense SDHB mutation (c.649C > T). Spectrometric analysis using tandem mass tags identified 151 proteins significantly differentially expressed in HNPGLs compared with normal nerves. Bioinformatics analyses confirmed the high level of enrichment of oxidative phosphorylation and metabolism pathways in HNPGLs. The mitochondrial complex subunits NDUFA2, NDUFA10, and NDUFA4, showed the most significantly increased expression and were localized predominantly in the cytoplasm of PGL-626 cells. The mitochondrial complex I inhibitor metformin exerted dose-dependent inhibitory effects on PGL-626 cells via cooperative down-regulation of NDUFA2, 4, and 10, with a significant decrease in the levels of reactive oxygen species and mitochondrial membrane potential. Further metabolomic analysis of PGL-626 cells showed that metabolites involved in central carbon metabolism in cancer and sphingolipid signaling pathways, pantothenate and CoA biosynthesis, and tryptophan and carbon metabolism were significantly altered after metformin treatment. Thus, this study provides insights into the molecular mechanisms underlying HNPGL tumorigenesis and identifies target correction of metabolic abnormalities as a novel therapeutic approach for this disease.

[Tumor necrosis factor α inhibits the migration of human oligodendrocyte precursor cells in vitro].

Objective To investigate the impact of tumor necrosis factor alpha (TNF-α) on the migration ability of oligodendrocyte precursor cells (OPCs) derived from human adult neural stem cells (NSCs) for transplantation therapy. Methods Flow cytometry was performed to detect the expressions of platelet derived growth factor receptor alpha (PDGFRα) and ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 (ST8SIA1/A2B5) in human OPCs. OPCs were cultured and incubated with 0, 10, 100, 200 ng/mL TNF-α for 18 hours. OPC viability was detected by CCK-8 assay and OPC migration was detected by TranswellTM migration assay. Results OPCs derived from human adult NSC specifically expressed PDGFRα (87.9%) and A2B5 (40.0%). Treatment with 10 ng/mL TNF-α had no impact on OPC viability while both 100 ng/mL and 200 ng/mL TNF-α treatments decreased OPC viability significantly. OPC migration was reduced significantly in 10 ng/mL TNF-α treated group compared with the blank control. Conclusion TNF-α inhibits the migration of the cultured OPCs.

Thermal Safety of Endoscopic Usage in Robot-Assisted Middle Ear Surgery: An Experimental Study.

Objectives: The widespread application of endoscopic ear surgery (EES), performed through the external auditory canal, has revealed the limitations of the one-handed technique. The RobOtol® (Collin ORL, Bagneux, France) otological robotic system has been introduced to enable two-handed procedures; however, the thermal properties of dedicated endoscopes, which are usually used in neurosurgery, called "neuro-endoscopes," have not yet been clarified for the robotic systems. In this study, we aimed to profile the thermal characteristics of two dedicated neuro-endoscopes, as compared to endoscopes used routinely in manual EES, called "oto-endoscopes," and defined by a smaller diameter and shorter length, and to discuss the safe application of robotic assistance in EES. Methods: Two neuro-endoscopes (3.3 mm, 25 cm, 0°/30°) were studied using two routine light sources (LED/xenon), and two routine oto-endoscopes (3 mm, 14 cm, 0°/30°) were initially measured to provide a comprehensive comparison. Light intensities and temperatures were measured at different power settings. The thermal distributions were measured in an open environment and a human temporal bone model of EES. The cooling measures were also studied. Results: Light intensity was correlated with stabilized tip temperatures (P < 0.01, R 2 = 0.8719). Under 100% xenon power, the stabilized temperatures at the tips of 0°, 30° neuro-endoscopes, and 0°, 30° oto-endoscopes were 96.1, 60.1, 67.8, and 56.4°C, respectively. With 100% LED power, the temperatures decreased by about 10°C, respectively. For the 0° neuro-endoscope, the illuminated area far away 1cm from the tip was below 37°C when using more than 50% both power, while this distance for 30° neuro-endoscope was 0.5 cm. In the EES temporal bone model, the round window area could reach 59.3°C with the 0° neuro-endoscope under 100% xenon power. Suction resulted in a ~1-2°C temperature drop, while a 10 mL saline rinse gave a baseline temperature which lasted for 2.5 min. Conclusion: Neuro-endoscope causes higher thermal releasing in the surgical cavity of ESS, which should be especially cautious in the robotic system usage. Applying submaximal light intensity, a LED source and intermittent rinsing should be considered for the safer robot-assisted EES using a neuro-endoscope that allows a two-handed surgical procedure.

Study on the Safety of Human Oligodendrocyte Precursor Cell Transplantation in Young Animals and Its Efficacy on Myelination.

Oligodendrocyte precursor cells (OPCs) can differentiate into myelinating oligodendrocytes during embryonic development, thereby representing an important potential source for myelin repair or regeneration. To the best of our knowledge, there are very few OPCs from human sources (human-derived OPCs [hOPCs]). In this study, we aimed to evaluate the safety and remyelination capacity of hOPCs developed in our laboratory, transplanted into the lateral ventricles of young animals. Several acute and chronic toxicity experiments were conducted in which different doses of hOPCs were transplanted into the lateral ventricles of Sprague-Dawley rats of different ages. The toxicity, biodistribution, and tumor formation ability of the injected hOPCs were examined by evaluating the rats' vital signs, developmental indicators, neural reflexes, as well as by hematology, immunology, and pathology. In addition, the hOPCs were transplanted into the corpus callosum of the shiverer mouse to verify cell myelination efficacy. Overall, our results show that transplanted hOPCs into young mice are nontoxic to their organ function or immune system. The transplanted cells engrafted in the brain and did not appear in other organs, nor did they cause tissue proliferation or tumor formation. In terms of efficacy, the transplanted hOPCs were able to form myelin in the corpus callosum, alleviate the trembling phenotype of shiverer mice, and promote normal development. The transplantation of hOPCs is safe; they can effectively form myelin in the brain, thereby providing a theoretical basis for the future clinical transplantation of hOPCs.