Endoscopic Management of Recurrent Epistaxis Caused by Retiform Hemangioendothelioma in a Child: A Case Report.

Retiform hemangioendothelioma (RH) is a rare intermediate (locally aggressive) vascular tumor that mostly affects the dermis of the trunk and limbs, but has never been reported in the inferior turbinate. A 10-year-old Chinese boy presented with recurrent epistaxis in his left nasal cavity and anemia for more than 2 years. Radiographic and electronic video laryngoscopic images showed an expansile mass in the left inferior turbinate. Endoscopic surgery and electrocautery were performed to resect the tumor beyond the macroscopic border. Histopathologically, the tissues were infiltrated by hyperplastic blood vessels arranged in a retiform pattern, and endothelial cells proliferate significantly in some areas. Immunohistochemistry showed a positive result for CD31, CD34, Fli-1, and ERG. No epistaxis, tumor recurrence, or metastasis was found on reexamination over 18 months after surgery.

Phospholipid-inspired alkoxylation induces crystallization and cellular uptake of luminescent COF nanocarriers.

The porous nature and structural variability of covalent organic frameworks (COFs) make them preferred for drug loading and delivery applications. However, most COF materials suffer from poor luminescent properties and inefficiency for cell uptake. Herein, we experimentally demonstrate the crucial role of long alkoxy chains in the synthesis of crystalline COF nanostructures with high cellular uptake efficiency. After luminescence integration through band engineering, the semiconducting COF exhibits an optical bandgap of 2.05 eV, an emission wavelength of 632 nm, a high quantum yield of 37 %, and excellent fluorescence stability (100 % at 3 h). Such excellent optical properties of the designed COF nanocarriers enable quantitative evaluations of cellular uptake and visual tracking of drug delivery. It was demonstrated that the cellular uptake efficiency was enhanced by orders of magnitude for the COF after the introduction of long n-octyloxy chains, which firstly delivered the anticancer camptothecin (CPT) to cell lysosomes, and then underwent "endo/lysosomal escape" to induce cell apoptosis. In vivo assay evidenced a significant enhancement in the therapeutic effect with a 96 % inhibition of tumor growth after 14 days of treatment. This progress sheds light on designing cutting-edge drug delivery nanosystems based on COF materials with integrated diagnostic and therapeutic functions.

A novel intronic variant causing aberrant splicing identified in two deaf Chinese siblings with enlarged vestibular aqueducts.

OBJECTIVE: We aimed to evaluate the genotype-phenotype relationship in two Chinese family members with enlarged vestibular aqueduct (EVA). METHODS: We collected blood samples and clinical data from each pedigree family member. Genomic DNA was isolated from peripheral leukocytes using standard methods. Targeted next-generation sequencing and Sanger sequencing were performed to find the pathogenic mutation in this family. Minigene assays were used to verify whether the novel intronic mutation SLC26A4c.765+4A>G influenced mRNA splicing. RESULTS: Hearing loss in the patients with EVA was diagnosed using auditory tests and imaging examinations. Two pathogenic mutations, c.765+4A>G and c.919-2A>G were detected in SLC26A4. In vitro minigene analysis confirmed that c.765+4A>G variant could cause aberrant splicing, resulting in skipping over exon 6. CONCLUSIONS: The SLC26A4c.765+4A>G mutation is the causative variant in the Chinese family with EVA. Particular attention should be paid to intronic variants.

Red-Fluorescent Covalent Organic Framework Nanospheres for Trackable Anticancer Drug Delivery.

Covalent organic frameworks (COFs) have emerged as promising drug carriers due to their structural variability, inherent porosity, and customizable functions. However, most COFs used in drug delivery suffer from low cellular bioavailability and poor luminescence properties. In this study, we designed a series of size-tunable, crystalline, and red-fluorescent COF nanospheres (COFNSs) for trackable anticancer drug delivery. The semiconducting COFNSs were prepared by condensations of 1,3,5-triformylbenzene (TFB) with various dihydrazide blocks through the Schiff-base reaction, resulting in red emission at 647 nm and excellent fluorescence stability (∼100% for 1 h). Such fluorescence property allowed for systematic investigation of the cellular endocytosis pathway of COFNSs, visualization of drug delivery, and observation of the cell apoptosis process. The COFNSs exhibited high cell viability (>90%), a loading capacity of 183 wt % for the anticancer drug camptothecin (CPT), and significant enhancement in inhibiting 4T1 cancers both in vitro and in vivo as the CPT nanocarrier. This progress presents a valuable approach to design COF nanocarriers with integrated fluorescent and drug delivery functions.

The mental health of paediatric cochlear implant recipients.

OBJECTIVES: To evaluate the mental health of paediatric cochlear implant users and analyse the relationship between six dimensions (movements, cognitive ability, emotion and will, sociality, living habits and language) and hearing and speech rehabilitation. METHODS: Eighty-two cochlear implant users were assessed using the Mental Health Survey Questionnaire. Age at implantation, time of implant use and listening modes were investigated. Categories of Auditory Performance and the Speech Intelligibility Rating Scale were used to score hearing and speech abilities. RESULTS: More recipients scored lower in cognitive ability and language. Age at implantation was statistically significant (p < 0.05) for movements, cognitive ability, emotion and will, and language. The time of implant usage and listening mode indicated statistical significance (p < 0.05) in cognitive ability, sociality and language. CONCLUSION: Timely attention should be paid to the mental health of paediatric cochlear implant users, and corresponding psychological interventions should be implemented to make personalised rehabilitation plans.

Research Advances on Deafness Genes Associated with Mitochondrial tRNA-37 Modifications.

As the most common cause of speech disorders, the etiological study of deafness is important for the diagnosis and treatment of deafness. The mitochondrial genome has gradually become a hotspot for deafness genetic research. Mitochondria are the core organelles of energy and material metabolism in eukaryotic cells. Human mitochondria contain 20 amino acids, except for tRNALeu and tRNASer, which have 2 iso-receptors, the other 18 amino acids correspond to unique tRNAs one by one, so mutations in any one tRNA may lead to protein translation defects in mitochondria and thus affect their oxidative phosphorylation process resulting in the corresponding disease phenotype. Mitochondrial tRNAs are extensively modified with base modifications that contribute to the correct folding of tRNAs and maintain their stability. Defective mitochondrial tRNA modifications are closely associated with the development of mitochondrial diseases. The in-depth study found that modification defects of mammalian mitochondrial tRNAs are associated with deafness, especially the nucleotide modification defect of mt-tRNA-37. This article reviews the research on mitochondrial tRNAs, nucleotide modification structure of mitochondrial tRNA-37, and nuclear genes related to modification defects to provide new ideas for the etiological study of deafness.

The effect of SLC26A4 gene mutations on long-term rehabilitative outcomes in cochlear implant patients.

BACKGROUND: SLC26A4 gene mutations related to hearing loss patients can obtain good hearing and speech rehabilitation effects after cochlear implantation (CI). OBJECTIVE: To explore the long-term rehabilitative outcomes of CI in patients with different SLC26A4 mutation groups. MATERIAL AND METHODS: Clinical data of 71 patients with SLC26A4 gene mutations who received CI in the Second Hospital of Lanzhou University from 2012 to 2015 were retrospectively reviewed. According to the genetic test results, use One-way ANOVA analysis to compare the differences in auditory results, categories of auditory performance (CAP) and speech intelligibility rating (SIR) index questionnaire scores and speech recognition rates among different groups in 4-5 years after CI. RESULT: Compared with other genotypes of SLC26A4, the patients with homozygous mutation of c.919-2A > G in SLC26A4 had better hearing aid threshold at 500 Hz and better recognition rates of Yangyang words than other monoallelic mutation groups after CI (p < .05). CONCLUSIONS AND SIGNIFICANCE: The most common hot spot mutation of SLC26A4 gene is c.919-2A > G. The patients with homozygous mutation of c.919-2A > G in SLC26A4 gene had partly better hearing and speech rehabilitation than other monoallelic mutation groups after CI.

Research on congenital severe-to-profound sensorineural hearing loss associated with central lucency of the bony island of the lateral semicircular canal.

BACKGROUND: Central lucency of the bony island of the lateral semicircular canal (LSCC) is commonly found in patients with congenital severe-to-profound sensorineural hearing loss (SNHL). OBJECTIVE: Exploring the significance of bony island lucency of LSCC in congenital severe-to-profound SNHL patients. MATERIAL AND METHODS: Retrospective measurements of the inner ear structures were made on axial temporal bone CT scans from 182 (364 ears) congenital severe-to-profound SNHL patients and 50 (100 ears) tympanic membrane perforation (TMP) patients. RESULTS: The incidence of bony island lucency of LSCC was 46.7% in the congenital severe-to-profound SNHL group and 0% in the TMP group. There was a statistically significant difference in inner ear structures among congenital severe-to-profound SNHL patients with normal inner ear structure and bony island lucency of LSCC, congenital severe-to-profound SNHL patients with normal inner ear structure and no bony island lucency of LSCC, and TMP patients. The importance of the bony island lucency of LSCC was further confirmed through multiple linear regression analysis. CONCLUSIONS AND SIGNIFICANCE: Bony island lucency may have significance in congenital severe-to-profound SNHL and may be a manifestation of largely overlooked SCC malformation or hypoplasia of the inner ear.

The value of nonverbal intelligence in cochlear implant.

BACKGROUND: Congenital sensorineural hearing loss is a common congenital condition. OBJECTIVES: The purpose of this study was to assess the correlation between nonverbal mental development and the effect of post-cochlear implant in children. MATERIAL AND METHODS: The study is a retrospective analysis of the CI program implemented at the ENT in the Lanzhou University Second Hospital (China). We reviewed data of 225 children who received CI between 2015 and 2018. Finally, 115 children met the inclusion criteria. Our hospital used The Griffith mental development scales to evaluate the preoperative non-verbal intelligence. The outcome of CI was evaluated using the categories of IT-MAIS, MUSS, CAP and SIR at 2 years after surgery. The associations between the preoperative non-verbal development quotient (DQ) and the postoperative outcomes were analyzed. RESULTS: Preoperative non-verbal DQ correlates with the long-term postoperative result, especially the Eye-hand co-ordination and Performance DQ. CONCLUSIONS AND SIGNIFICANCE: Preoperative non-verbal intelligence would predict postoperative effect. The single postoperative scale does not fully reflect the postoperative result.

Analysis of GJB2 Gene Mutations in 1330 Deafness Cases of Major Ethnic Groups in Northwest China.

Background: The GJB2 gene is the most common deafness gene, and epidemic characteristics have obvious racial specificity. Our study aimed to investigate the prevalence and ethnic specificity of the GJB2 gene in deafness in major ethnic groups in Northwest China, evaluate the value of molecular screening for deafness in minority populations, and explore the strategies and methods for genetic diagnosis. Methods: Ethics approval was obtained to collect 1330 cases of moderate to very severe nonsyndromic sensorineural deafness in northwestern China. The mutation characteristics of ethnic minorities were analyzed and compared with those of 464 patients with nonsyndromic sensorineural deafness among ethnic Han in the northwestern from research group by Sequence Scanner V25.0. Then, we analyzed the ethnic specificity of the mutations. Results: A total of 15 GJB2 sequence changes were detected in 1330 minority patients. The study showed that the allele frequency in Tibetan patients was significantly lower than that in Hui and Dongxiang patients, that in Uygur patients was significantly lower than that in Han and Hui patients, and that in Kazak and Tibetan patients was significantly lower than that in Han patients, and the differences between other ethnic groups were not statistically significant. Each ethnic group has a unique GJB2 gene mutation spectrum, and its hotspot mutation distribution has its own characteristics, with c.235delC, c.109 G > A, c.299-300delAT, and c.35delG being common. Conclusions: It has been confirmed that GJB2 gene mutation has a high prevalence in patients with nonsyndromic sensorineural hearing loss in Northwest China. Each ethnic group has a unique mutation spectrum for the GJB2 gene, which is related to its genetic background. It is necessary to develop a corresponding gene diagnosis strategy according to the hotspot mutations and mutation spectrum of each ethnic group.

Pharyngeal Ectopic Thymus: A Case Report.

Pharyngeal ectopic thymus is a rare cause of pharyngeal masses and is rarely considered in the differential diagnosis of neck and head masses in children. In this paper, the case of an infant with a pharyngeal ectopic thymus is presented and our intraoral surgical approach in the patient's treatment is described.

[Computer tomography demonstrations of single-sided deafness].

Objective:To investigate the distribution of common inner ear and internal auditory canal malformations in children with single-sided deafness（SSD） ,and to explore the imaging etiology of SSD by comparing the quantitative parameters of key bone structures between deaf and normal ears in children with congenital SSD. Method:Forty children with SSD diagnosed in the Second Hospital of Lanzhou University from September 2016 to March 2019 were collected. All of them underwent HRCT examinations of temporal bone . The area of bone island, the width of vestibular, the width of internal auditory canal, the height of cochlear and the width of cochlear basal axis were measured. Paired t test was used to compare the difference between the hearing abnormality and normal hearing in children with SSD. Result:The rate of inner ear deformity was 62.5% in SSD group,the most common deformity was cochlear nerve canal deformity, 20 cases （50.0%） of cochlear canal stenosis and 3 cases （7.5%） of cochlear canal atresia.The second most common deformity was internal auditory canal deformity, including 5 cases （12.5%） of internal auditory canal stenosis and 1 case （2.5%） of internal auditory canal atresia. Other malformations included 1 case（2.5%） of RO, 2 cases （5.0%） of incomplete partition （IP） type II and 1 case （2.5%） of enlargement of vestibular aqueduct （EVA）. There are no significant difference in the measured results of the key structures of the inner ear between two groups except the width of cochlear nerve canal, internal auditory canal and the area of bone island. Conclusion:The main inner ear deformities in children with SSD are cochlear nerve canal stenosis and inner auditory canal stenosis. HRCT of temporal bone has high diagnostic value for inner ear deformities in children with SSD.

Analysis between phenotypes and genotypes of inner ear malformation.

BACKGROUND: The clinical characteristics of LVAS have attracted more and more attention, its audiology and imaging features have also been deeply studied. OBJECTIVE: To analyze phenotypes, genotypes of EVA, and find out the relationship between them. METHODS: Sixty EVA patients were tested by audiometry, temporal bone high-resolution CT and inner ear MRI. SNPscan technology were carried out after the patients signed informed consent. SPSS19.0 software was used. RESULT: 1. Three types malformations include EVA, EVA with Mondini and Mondini were found. They accounted for 48.20%, 40.10%, and 11.70%. 2. The SLC26A4 gene mutation frequency was (47/53) 88.68% in EVA patients. The most common genotype was c.919-2A > G/c.919-2A > G, accounting for 28.30%. The most common mutation type was c.9I9-2A > G. 3. GJB2 and SLC26A4 gene mutation frequencies were significantly different (χ2＝65.185, p<.001). CONCLUSIONS: 1. EVA patients with severe sensorineural hearing loss were always diagnosed in childhood and Cochlear implantation was feasible for these patients with the bilateral hearing loss. 2. SLC26A4 gene was closely related to EVA. 3. GJB2 and mtDNA genes were not responsible for EVA. SIGNIFICANCE: The relationship between genotype and clinical phenotype provides a theoretical basis for future gene diagnosis and prevention and treatment of LVAS.

The deafness-causing mutation c.508_511dup in the GJB2 gene and a literature review.

CONCLUSIONS: The mutation c.508_511dup in GJB2 gene has been incorrectly named as other mutations. It is essential to standardize mutation nomenclature to describe complex mutations. OBJECTIVES: This paper aimed to verify a series of patients with the frame-shift mutation c.508_511dup in the GJB2 gene and review the literature on related mutations. METHODS: All the included patients with non-syndromic hearing loss (NSHL) carried the 504insAACG or c.508_511dup mutation of the GJB2 gene in the present study. Their parents were encouraged to participate. After written informed consent and clinic data had been obtained, genomic DNA was extracted from venous blood of participants. The target fragments were amplified by polymerase chain reaction (PCR) and subjected to bidirectional sequencing to identify sequence variations. RESULTS: A total of 14 patients with prelingual NSHL and 6 normal parents were recruited. Genotyping revealed that one mutation, c.508_511dup (not 504insAACG), was homozygous in 1 patient, heterozygous in 2 patients and 3 parents, and compound heterozygous in 11 patients. Twelve patients had hearing loss caused by c.508_511dup in a homozygous or compound heterozygous form, and further study showed that it was wrongly named as 504insAACG. Additionally, according to the standard nomenclature, the previously reported mutations with distinct names from the literature review may be replaced by c.508_511dup.

Analysis of common deafness gene mutations in deaf people from unique ethnic groups in Gansu Province, China.

CONCLUSIONS: The GJB2 gene mutation characteristic of Dongxiang was the interaction result of ethnic background and geographical environment, and Yugur exhibited the typical founder effect. The SLC26A4 gene mutation characteristic of Dongxiang was related to caucasian backgrounds and selection of purpose exons, i.e. ethnic background and the penetrance of ethnic specificity caused the low mtDNA1555A>G mutation frequency in Dongxiang. OBJECTIVES: To determine the prevalence of GJB2 and SLC26A4 genes and mtDNA1555A>G mutations and analyze the ethnic specificity in the non-syndromic sensorineural hearing loss (NSHL) of unique ethnic groups in Gansu Province. METHODS: Peripheral blood samples were obtained from Dongxiang, Yugur, Bonan, and ethnic Han groups with moderately severe to profound NSHL in Gansu Province. Bidirectional sequencing (or enzyme digestion) was applied to identify the sequence variations. RESULTS: The pathogenic allele frequency of the three gene mutations was different. The frequency of the GJB2 gene among the Dongxiang, Yugur, Bonan, and ethnic Han groups was 9.03%, 12.5%, 5.88%, and 12.17%, respectively. No difference was found between the ethnic groups. The frequencies of the SLC26A4 genes were 3.23%, 8.33%, 0%, and 9.81%, respectively. The mutation frequency of mtDNA1555A>G was 0%, 0%, 0%, and 6.03%, respectively. No difference was found between the ethnic groups, except for the Dongxiang and ethnic Han groups, both in SLC26A4 gene and mtDNA1555A>G.