Diagnosis, differential diagnosis, and treatment for sudden sensorineural hearing loss: Current otolaryngology practices in China.

Introduction: Although sudden sensorineural hearing loss (SSNHL) has been attempted to be understood for 70 years, diagnosis and treatment strategies still have strong heterogeneity worldwide, which are reflected in the guidelines issued by countries and the clinical practice of otolaryngologists. Methods: Questionnaires were sent to registered otolaryngologists nationwide via an online questionnaire system. We investigated the current views and clinical practices of otolaryngologists in mainland China about the diagnosis, examination, and treatment strategies of SSNHL. Results: Most otolaryngologists supported diagnostic classification via audiograms. Regional economic situation and hospital grade affected application strategies for differential diagnosis. Regarding corticosteroid therapy, 54.9% of respondents opted to discontinue the drug 5 days after systemic administration. Both intratympanic therapy and post-auricular injections were selected by more than half of the respondents as initial and salvage treatments. Discussion: Chinese otolaryngologists exhibit heterogeneity in clinical practices for SSNHL, including distinct approaches to combination therapy and local application of steroids. This study pointed out Chinese doctors' similarities, differences, and unique strategies in diagnosing and treating SSNHL and analyzed the possible reasons to help the world understand the current otolaryngology practices in China.

Dynamic changes of otolith organ function before and after repositioning in patients with benign paroxysmal positional vertigo detected by virtual reality auxiliary technology: A cohort study.

Objectives: To dynamically investigate otolith function in patients with benign paroxysmal positional vertigo (BPPV) before, after, and 1 month after repositioning, and explore the possible compensation mechanisms. Methods: Thirty-six patients confirmed with BPPV (canal lithiasis) treated in our hospital between August 2020 and March 2021, as well as 36 health controls matched for age and gender (normal control group, NC group) were enrolled. For NC group, the virtual reality (VR) auxiliary static subjective visual vertical (SVV), subjective visual horizontal (SVH), and SVV of dynamic unilateral centrifugation (DUC), were measured at inclusion. For the BPPV group, visual analog scale (VAS) was used to assess the vertigo degree, while static SVV, SVH, and DUC were performed before, after, and 1 month after repositioning. First, we compare the deviations of SVV0/SVH0° when the subject's head is in the positive position, and SVV of DUC between BPPV and NC groups before repositioning, after which we compared the deviations in SVV45, SVV90, SVH45, SVH90°, and SVV of DUC between the affected and unaffected sides before repositioning. Finally, paired t-test was used to compare the VAS score, deviations in static SVV0, SVV45, SVV90, SVH0, SVH45, and SVH90°, and deviations in SVV of DUC before, after, and 1 month after repositioning. (Here, 0, 45, and 90° refer to the angle which the center axis of head deviates from the gravity line.). Results: SVV0 SVH0°, and SVV of DUC at 120 and 180°/s 0 significantly differed between BPPV and NC group before repositioning. The deviations in SVV45, SVV90, SVH45, SVH90°, and SVV of DUC at 120°/s-2 and 180°/s-4.5 did not significantly differ between bilateral sides in BPPV patients before repositioning. The deviation in SVH90° was significantly lower after repositioning than before. The deviation in SVH45° was significantly higher 1 month after repositioning than before. The deviation angle of SVV of DUC at 180°/s-0 was significantly lower after repositioning than before. The vertigo VAS score of patient with BPPV continued to decrease after repositioning. Conclusion: Before repositioning, the otolithic organ function of BPPV patients was obviously impaired, with no significant difference between the healthy and affected ear. After repositioning, there was a transient recovery of otolithic organ dysfunction followed by a sustained decline to similar levels to before repositioning.

Corrigendum: Overexpression of mGluR7 in the Prefrontal Cortex Attenuates Autistic Behaviors in Mice.

[This corrects the article DOI: 10.3389/fncel.2021.689611.].

Overexpression of mGluR7 in the Prefrontal Cortex Attenuates Autistic Behaviors in Mice.

Autism spectrum disorder (ASD) is associated with a range of abnormalities pertaining to socialization, communication, repetitive behaviors, and restricted interests. Owing to its complexity, the etiology of ASD remains incompletely understood. The presynaptic G protein-coupled glutamate receptor metabotropic glutamate receptor 7 (mGluR7) is known to be essential for synaptic transmission and is also tightly linked with ASD incidence. Herein, we report that prefrontal cortex (PFC) mGluR7 protein levels were decreased in C57BL/6J mice exposed to valproic acid (VPA) and BTBR T+ Itpr3tf/J mice. The overexpression of mGluR7 in the PFC of these mice using a lentiviral vector was sufficient to reduce the severity of ASD-like behavioral patterns such that animals exhibited decreases in abnormal social interactions and communication, anxiety-like, and stereotyped/repetitive behaviors. Intriguingly, patch-clamp recordings revealed that the overexpression of mGluR7 suppressed neuronal excitability by inhibiting action potential discharge frequencies, together with enhanced action potential threshold and increased rheobase. These data offer a scientific basis for the additional study of mGluR7 as a promising therapeutic target in ASD and related neurodevelopmental disorders.

[Clinical and genetic analysis of a child with 2q37 deletion syndrome resulting from a translocation involving chromosome satellite].

OBJECTIVE: To carry out cyto- and molecular genetic testing for a child featuring facial dysmorphism and attention deficit and hyperactive disorder. METHODS: The child was subjected to routine peripheral blood lymphocyte chromosomal karyotyping, fluorescence in situ hybridization (FISH) and single nucleotide polymorphism array (SNP-array) analyses. RESULTS: The child's facial dysmorphism included low-set ears, curly ear auricle, protuberance of eyebrow arch, nostril notch, short and flat philtrum and thin upper lip. SNP-array revealed that he has carried a 4.883 Mb deletion at 2q37. His chromosomal karyotype was ultimately determined as 45, XY, der(2;21) (2pter→ 2q37.3::21p13→ 21p10::20p10→ 20pter), der(20) (21qter→ 21q10::20q10→ 20qter). CONCLUSION: A rare case of 2q37 deletion syndrome involving three chromosomes was discovered. Combined use of various cyto- and molecular genetic techniques is crucial for the diagnosis of chromosomal abnormalities with complex structures.

[Analysis of a Chinese pedigree with autosomal dominant Charcot-Marie-Tooth disease type 2A2A].

OBJECTIVE: To explore the genetic basis of a pedigree affected with peroneal muscular atrophy. METHODS: Neuroelectrophysiological examination and whole exome sequencing were carried out for the proband, a six-year-and-ten-month-old boy. Suspected variant was verified in his family members through Sanger sequencing. Bioinformatic analysis was carried to predict the conservation of amino acid sequence and impact of the variant on the protein structure and function. RESULTS: Electrophysiological examination showed demyelination and axonal changes of motor and sensory nerve fibers. A heterozygous missense c.1066A>G (p. Thr356Ala) variant was found in exon 11 of the MFN2 gene in the proband and his mother, but not in his sister and father. Bioinformatic analysis using PolyPhen-2 and Mutation Taster software predicted the variant to be pathogenic, and that the sequence of variation site was highly conserved among various species. Based no the American College of Medical Genetics and Genomics standards and guidelines, the c.1066A>G (p. Thr356Ala) variant of MFN2 gene was predicted to be likely pathogenic (PS1+ PM2+ PP3+ PP4). CONCLUSION: The heterozygous missense c.1066A>G (p.Thr356Ala) variant of the MFN2 gene probably underlay the disease in the proband, and the results have enabled genetic counseling and prenatal diagnosis for this family.

[Analysis of clinical characteristics of 87 patients with cochlear migraine].

Objective:The aim of this study is to analyze the clinical features of cochlear migraine. Methods:The clinical data of cases of cochlear migraine were collected, and the clinical symptoms and hearing examination results were analyzed. Results:The ratio of male to female patients with cochlear migraine was 1∶3.1; the peak incidence was between 30 to 60 years old; the clinical symptoms were tinnitus in 61 people（70%）, mild hearing loss in 52 people（60%）, aural fullness in hyperacusis in 13 people（15%）, auditory allergy in 9 people（10%） and otalgia in 5 people（6%）; the audiology characteristic was that 61.5%（32/52） of patients with hearing loss showed mild high-frequency neurological hearing loss, 34.6%（18/52） of patients showed mild low-frequency neurological hearing loss, and 3.8%（2/52） of patients showed full-frequency mild neurological hearing loss; the effective rate of tinnitus treatment was 57.4%, the effective rate of hearing loss was 71.2%, and the effective rate of aural fullness was 69.2%, the effective rate of hyperacusis is 66.7% and the effective rate of otalgia is 60.0%. Conclusion:The clinical characteristics of cochlear migraine are summarized, which provides a basis for the intervention of anti-migraine treatment programs for inner ear diseases.

[Analysis of MCCC2 gene variant in a pedigree affected with 3-methylcrotonyl coenzyme A carboxylase deficiency].

OBJECTIVE: To explore the genetic basis for a child with clinically suspected 3-methylcrotonyl-coenzyme A carboxylase deficiency (MCCD). METHODS: Genomic DNA was extracted from peripheral blood samples of the proband and her parents. Whole exome sequencing was used to screen pathogenic variant in the proband. Suspected variant was verified by Sanger sequencing. Impact of the variant on the structure and function of protein product was analyzed by using bioinformatic software. RESULTS: Sanger sequencing showed that the proband has carried homozygous missense c.1342G>A (p.Gly448Ala) variant of the MCCC2 gene, for which her mother was a heterozygous carrier. The same variant was not detected in her father. The variant was predicted to be pathogenic by PolyPhen-2 and Mutation Taster software, and the site was highly conserved among various species. Based on the American College of Medical Genetics and Genomics standards and guidelines, the c.1342G>A (p.Gly448Ala) variant of MCCC2 gene was predicted to be likely pathogenic(PM2+PP2-PP5). CONCLUSION: The homozygous missense variant of the MCCC2 gene c.1342G>A (p.Gly448Ala) probably underlay the molecular pathogenesis of the proband. Genetic testing has confirmed the clinical diagnosis.

Using a cartoon questionnaire to improve consent process in children: a randomized controlled survey.

OBJECTIVE: The aim of the study was to evaluate the effectiveness of an audio and animated cartoon questionnaire (AACQ) at improving consent process in child for biospecimen donation. METHODS: A multi-center randomized and controlled survey was performed at two pediatric hospitals in China from 2019 to 2020. Children aged from 7 to 18 years in the pediatric surgery wards were invited to investigate the participants' willingness and attitudes for donating biospecimens. A total of 264 children, including 119 in the AACQ group and 145 in the TQ group, and 67 parents of children were analyzed. A separate knowledge test was acquired in the questionnaires. RESULTS: Our findings showed that the response rate of the AACQ group (89.85%) was significantly higher than that of the TQ group (68.44%; p < 0.001). AACQ can improve the child's understanding, increase children's engagement in biospecimen donation, reduced the differences in selected characteristics affecting children understanding, and enhanced their risk awareness of donating biospecimens. We also found that increasing pain and privacy disclosure were the most popular concern among children for the refusal to donate biospecimens. CONCLUSIONS: AACQ is an effective and standardized tool of content delivery to children from the surgical wards. Children who fully understood of biospecimen donation are suggested to participate in the consent signing. IMPACT: Using audio and animated cartoon questionnaire is a more effective and standardized tool of content delivery to children. This study expanded the use of an animated cartoon to a children's survey. Audio and animated cartoon questionnaire (AACQ) can improve the child's understanding, increase children's engagement in biospecimen donation compared to text questionnaire (TQ) group, and enhanced their risk awareness of donating biospecimens. More AACQ should be used with children in the future to effectively deliver content to children and improve children's participation in the survey.

Comparison of Structure and Properties of Mo2FeB2-Based Cermets Prepared by Welding Metallurgy and Vacuum Sintering.

At present, most Mo2FeB2-based cermets are prepared by vacuum sintering. However, vacuum sintering is only suitable for ordinary cylinder and cuboid workpieces, and it is difficult to apply to large curved surface and large size workpieces. Therefore, in order to improve the flexibility of preparing Mo2FeB2 cermet, a flux cored wire with 70% filling rate, 304 stainless steel, 60 wt.% Mo powder and 40 wt.% FeB powder was prepared. Mo2FeB2 cermet was prepared by an arc cladding welding metallurgy method with flux cored wire. In this paper, the microstructure, phase evolution, hardness, wear resistance and corrosion resistance of Mo2FeB2 cermets prepared by the vacuum sintering (VM-Mo2FeB2) and arc cladding welding metallurgy method (WM-Mo2FeB2) were systematically studied. The results show that VM-Mo2FeB2 is composed of Mo2FeB2 and γ-CrFeNi.WM-Mo2FeB2 is composed of Mo2FeB2, NiCrFe, MoCrFe and Cr2B3. The volume fraction of hard phase in WM-Mo2FeB2 is lower than that of VM-Mo2FeB2, and its hardness and corrosion resistance are also slightly lower than that of VM-Mo2FeB2, but there are obvious pores in the microstructure of VM-Mo2FeB2, which affects its properties. The results show that WM-Mo2FeB2 has good diffusion and metallurgical bonding with the matrix and has no obvious pores. The microstructure is compact and the wear resistance is better than that of VM-Mo2FeB2.

Effect of Rare Earth on Microstructure and Wear Resistance of In-Situ-Synthesized Mo2FeB2 Ceramics-Reinforced Fe-Based Cladding.

Mo2FeB2 ceramics-reinforced Fe-based cladding with various rare earth (RE) concentrations were prepared by the carbon arc surfacing process. The effects of RE content on the microstructure, phase composition, hardness and wear resistance of the cladding were systematically discussed. Meanwhile, the area fraction and grain size of Mo2FeB2 phase were exactly measured. Moreover, the refining mechanism of rare earth Y was analyzed. Results revealed that the claddings consisted of Mo2FeB2, FeCr, MoB and CrB. Adding the rare-earth Y decreased the grain sizes of Mo2FeB2 phase. Furthermore, grain-refining effects of Mo2FeB2 phase were significant when the RE content was 2% and hard phases evenly distributed in the cladding. In addition, the maximum microhardness value of claddings was about 1078 HV. The claddings with 2% RE contents had better wear resistance, which was equivalent to a sintered sample.

Identification of hydatidosis-related modules and key regulatory genes.

BACKGROUND: Echinococcosis caused by larval of Echinococcus is prevalent all over the world. Although clinical experience showed that the presence of tapeworms could not be found in liver lesions, the repeated infection and aggravation of lesions still occur in the host. Here, this study constructed a multifactor-driven disease-related dysfunction network to explore the potential molecular pathogenesis mechanism in different hosts after E.multilocularis infection. METHOD: First, iTRAQ sequencing was performed on human liver infected with E.multilocularis. Second, obtained microRNAs(miRNAs) expression profiles of humans and canine infected with Echinococcus from the GEO database. In addition, we also performed differential expression analysis, protein interaction network analysis, enrichment analysis, and crosstalk analysis to obtain genes and modules related to E.multilocularis infection. Pivot analysis is used to calculate the potential regulatory effects of multiple factors on the module and identify related non-coding RNAs(ncRNAs) and transcription factors(TFs). Finally, we screened the target genes of miRNAs of Echinococcus to further explore its infection mechanism. RESULTS: A total of 267 differentially expressed proteins from humans and 3,635 differentially expressed genes from canine were obtained. They participated in 16 human-related dysfunction modules and five canine-related dysfunction modules, respectively. Both human and canine dysfunction modules are significantly involved in BMP signaling pathway and TGF-beta signaling pathway. In addition, pivot analysis found that 1,129 ncRNAs and 110 TFs significantly regulated human dysfunction modules, 158 ncRNAs and nine TFs significantly regulated canine dysfunction modules. Surprisingly, the Echinococcus miR-184 plays a role in the pathogenicity regulation by targeting nine TFs and one ncRNA in humans. Similarly, miR-184 can also cause physiological dysfunction by regulating two transcription factors in canine. CONCLUSION: The results show that the miRNA-184 of Echinococcus can regulate the pathogenic process through various biological functions and pathways. The results laid a solid theoretical foundation for biologists to further explore the pathogenic mechanism of Echinococcosis.

A Lactococcus lactis-vectored oral vaccine induces protective immunity of mice against enterotoxigenic Escherichia coli lethal challenge.

Enterotoxigenic Escherichia coli (ETEC) is a global primary pathogenic bacterium causing diarrhoea in human and a wide variety of neonatal animals. Lactococcus lactis as non-pathogenic and food-grade lactic acid bacteria has already been explored as a vector for mucosal vaccine. Here, the current study was undertaken to evaluate the live recombinant L. lactis (rL. lactis) vaccine expressing the trivalent enterotoxin protein STa-LTB-STb and the F5 fimbrial antigen (SLS-F5) with OmpH of Yersinia enterocolitica in protection against ETEC. Western blot confirmed the expression of fusion protein SLS-F5-OmpH in nisin-controlled expression (NICE) system. Mice orally immunized with rL. lactis-SLS-F5-OmpH were observed to produce high levels of mucosal SIgA and serum IgG antibodies, while also inducing increases in the production of CD4+ and CD8+ T cells, lymphocyte proliferation, and secretion of cytokines. Moreover, orally immunized mice produced complete protection after ETEC challenge. The above results suggested that rL. lactis-SLS-F5-OmpH has the potential as a candidate for oral vaccine against ETEC.

LncRNA DLX6-AS1 promotes laryngeal squamous cell carcinoma growth and invasion through regulating miR-376c.

Accumulating evidence showed that lncRNAs play important roles in tumour development. Recently, a novel lncRNA DLX6-AS1 was found to be overexpressed in some tumors such as lung adenocarcinoma, renal cell carcinoma and hepatocellular carcinoma. However, the functional roles of DLX6-AS1 in laryngeal squamous cell carcinoma (LSCC) are still unclear. In the study, we showed that the expression level of DLX6-AS1 was upregulated in the LSCC samples compared to the noncancerous tissues. By using CCK-8 analysis, we demonstrated that knockdown expression of DLX6-AS1 suppressed the Hep2 cell growth. DLX6-AS1 knockdown inhibited the Hep2 cell cycle and invasion. MiR-376c was identified to have the complementary binding sites with the DLX6-AS1. By luciferase reporter assay, we indicated that overexpression of miR-376c inhibited the luciferase activity of wild-type DLX6-AS1, but it failed to suppress luciferase activity of mutated one. DLX6-AS1 knockdown enhanced the expression of miR-376c in the Hep2 cell. Moreover, we showed that the expression level of miR-376c was lower in the LSCC samples than in the noncancerous tissues and the expression of miR-376c was negatively correlated with expression of DLX6-AS1 in LSCC tissues. Ectopic expression of miR-376c suppressed cell proliferation, cycle and invasion of LSCC cell. DLX6-AS1 knockdown suppressed cell proliferation, cycle and invasion via regulating miR-376c expression. These data proved that lncRNA DLX6-AS1 might play as an oncogene in LSCC development and tumorigenesis.

[Application of multiple MLL gene rearrangement detection techniques for children with acute mononuclear leukemia].

OBJECTIVE: To assess the value of detecting multiple rearrangements of MLL gene in children with acute mononuclear leukemia (AML). METHODS: Eighty six children with AML were analyzed by fluorescence in situ hybridization (FISH), chromosomal karyotyping and multiplex reverse transcription-PCR (RT-PCR). RESULTS: Cross signals were detected by FISH in 26 cases, and 30.2% were detected with MLL gene rearrangements. R-band karyotyping analysis revealed 14 translocations with breakages involving 11q23 and 5 other aberrations, which yielded an overall detection rate of 22.1%. Multiple RT-PCR has detected 12 fusion genes produced by the MLL translocation, which yielded a detection rate of 14.0%. A significant difference was found in the detection rate of the three methods (P< 0.05). CONCLUSION: Combined use of FISH, chromosomal karyotyping and multiplex RT-PCR can improve the detection of MLL gene rearrangements and provide important clues for clinical diagnosis, treatment and prognosis of AML.

MicroRNA-H4-5p encoded by HSV-1 latency-associated transcript promotes cell proliferation, invasion and cell cycle progression via p16-mediated PI3K-Akt signaling pathway in SHSY5Y cells.

Herpes simplex virus 1 (HSV-1) microRNAs (miRNAs) mostly located in transcription-associated transcript (LAT) region have been identified that play critical roles in the intricate host-pathogen interaction networks. Increasing evidences throw new insight into the role of miRNA-mediated miRNA-mRNA cross-talk in HSV-1 latent or acute infection. In the present study, we found that hsv-1 miR-H4-5p (here termed as miR-H4b) can down-regulate the expression of cyclin-dependent kinase inhibitor 2A (CDKN2A, p16) in neuroblastoma (SHSY5Y) cell lines. Decreased expression of miR-H4b was directly related to attenuated cell proliferation and invasion as well as malfunction of cell cycle in recombinant SHSY5Y cells that stably expressing miR-H4b. Bioinformatics analysis and luciferase assays demonstrated miR-H4b can directly target p16 mRNA. MiR-H4b exerts its pro-proliferation function through inhibition of the p16-related PI3K-Akt pathways. Our findings provide, for the first time, significant clues regarding the role of herpesvirus-encoded miRNAs as a viral modulator to host cells.

Evaluation of CYP2C9 Activity in Rats: Use of Tolbutamide Alone and in Combined with Bupropion.

A "cocktail"of several probe drugs is often used to evaluate metabolic activity of multiple cytochrome P450 enzymes in one session. Some interactions among probe drugs can appear and may impact the rate of biotransformation of other ones. Our presented work was aimed on the influence of bupropion on cytochrome P450-mediated metabolism of tolbutamide. The biotransformation rates of tolbutamide administered either separately or in combined with bupropion were compared in this study. The results revealed that bupropion had no significant effect on tolbutamide hydroxylation. Thus, due to stability in cytochrome P450 enzyme metabolic activity in the case of combining of two model probe drugs the procedure can show to no extent differential results comparing to the single-marker use.

Codonopsis pilosula (Franch) Nannf total alkaloids potentiate neurite outgrowth induced by nerve growth factor in PC12 cells.

AIM: To explore the effect of Codonopsis pilosula (Franch) Nannf total alkaloids (DSA) on differentiation induced by nerve growth factor (NGF) in PC12 cells. METHODS: After culturing PC12 cells with DSA in the presence or absence of NGF, neurite outgrowth in PC12 cells and correlated protein kinases were assayed. RESULTS: DSA alone did not exhibit neuritogenic activity, but caused a significant enhancement of NGF (2 microg/L)-induced neurite outgrowth in PC12 cells, and increased the phosphorylation of mitogen-activated protein kinase (MAPK). Furthermore, this enhancing effect was completely blocked by a specific MAPK kinase inhibitor, PD98059. CONCLUSION: DSA enhanced the NGF-induced neurite outgrowth in PC12 cells by amplifying an up-stream step of the MAPK-dependent signaling pathway.

[Combined reconstruction of tympanic membrane and posterior wall of external ear canal with cartilage].

OBJECTIVE: To study the reconstruction technique of tympanic membrane and posterior wall of external ear canal with auricular cartilage at same time. METHOD: The tympanic membrane and posterior wall of external ear canal of 43 cases of chronic suppurative otitis media were reconstructed with auricular cartilage after mastoidectomy between 1995-2000. The results were compared with that of without reconstruction of the posterior wall of external canal group of 60 ears in same period. RESULT: The average follow-up period was 32 months, 3 cases were faced in all of 43 cases, the others were healed in one stage. Postoperative period to be a dry ear was significantly shorter in the reconstruction group than in the canal-wall-down and open group (t-test, t = 3.98, < 0.01). The rezidive results is statistic not significant between this two groups. The patients of both groups have had good hearing results. CONCLUSION: The auricular cartilage is a good material for the reconstruction of tympanic membrane and posterior wall of the external auditory canal. It can not only reduce the time of drying ear, improve the hearing results, but also avoid the second operation. The quality of the patients life can be improved.