[Genetic analysis of a child with Complex cortical dysplasia with other brain malformations type 6 due to a p.M73V variant of TUBB gene].

OBJECTIVE: To explore the genetic basis for a child with multiple malformations. METHODS: A child who had presented at Shanxi Provincial Children's Hospital in February 2021 was selected as the study subject. Clinical data of the patient was collected, and whole exome sequencing (WES) was carried out to screen pathogenic variants associated with the phenotype. Candidate variant was validated by Sanger sequencing of her family members. RESULTS: The child had normal skin, but right ear defect, hemivertebral deformity, ventricular septal defect, arterial duct and patent foramen ovale, and separation of collecting system of the left kidney. Cranial MRI showed irregular enlargement of bilateral ventricles and widening of the distance between the cerebral cortex and temporal meninges. Genetic testing revealed that she has harbored a heterozygous variant of NM_178014.4: c.217A>G (p.Met73Val) in the TUBB gene, which was unreported previously and predicted to be likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). The child was diagnosed with Complex cortical dysplasia with other brain malformations 6 (CDCBM6). CONCLUSION: CDCBM is a rare and serious disease with great genetic heterogeneity, and CDCBM6 caused by mutations of the TUBB gene is even rarer. Above finding has enriched the variant and phenotypic spectrum of the TUBB gene, and provided important reference for summarizing the genotype-phenotype correlation of the CDCBM6.

Correlation of TGF-ß signaling pathway gene polymorphisms with unexplained recurrent spontaneous abortion.

BACKGROUND: The association of key genes in the transforming growth factor-ß (TGF-ß) signaling pathway and their gene polymorphisms with unexplained recurrent spontaneous abortion (URSA) is unclear. OBJECTIVE: To investigate the association of gene polymorphisms related to the TGF-ß signaling pathway in URSA women. METHODS: The study population consisted of 80 women with URSA and 90 normal control women, of which 10 women with URSA and 10 normal control women underwent high-throughput sequencing to select loci, and the remaining 70 women with URSA and 80 normal control women underwent flight mass spectrometry experiments to verify gene loci polymorphism. A total of 7 polymorphic loci in interleukin-6 (IL-6), TGF-ß1, TNF-α, SMAD1, and TNFRSF4 genes were screened by high-throughput sequencing combined with a review of databases. An SNP flight mass spectrometer (Mass ARRAY detection system) was applied to detect the polymorphisms and their frequencies in 70 women with URSA and 80 normal control women at the 7 gene loci. RESULTS: Among the 7 loci of IL-6, TGF-ß1, TNF-α, SMAD1, and TNFRSF4 genes, 2 loci were found to have significantly different allele and genotype frequency distributions between the 70 URSA and 80 normal controls, one was the IL-6 gene -174G/C locus (rs1800795), the risk of disease was 2.636 and 3.231 times higher in individuals carrying the C allele and CC genotype than in those carrying the G allele and GG genotype, respectively; the other was the TGF-ß1 gene -509T/C locus (rs1800469), and the risk of disease was 1.959 and 3.609 times higher in individuals carrying the T allele and TT genotype than in those carrying the C allele and CC genotype, respectively. The remaining 5 genetic loci have no statistically significant. CONCLUSION: IL-6 gene -174G/C locus (rs1800795) genotype CC and allele C may be the causative factor of URSA, TGF-ß1 gene -509T/C locus (rs1800469) genotype TT and allele T may be the causative factor of URSA, and polymorphisms of the 2 loci may be associated with URSA.

Diagnostic value of CBCT in Chinese children with adenoid hypertrophy.

Objective: The main objectives of the study were to investigate the reliability and accuracy of cone-beam computed tomography (CBCT) in the diagnosis of adenoid hypertrophy in Chinese children and to evaluate its value in clinical diagnosis. Methods: From January 2019 to January 2020, 300 children with sleep snoring in Xinhua Hospital Affiliated to Medical College of Shanghai Jiaotong University were retrospectively studied. All patients underwent nasopharyngoscopy (NE) and CBCT scanning. The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, and negative likelihood ratio of CBCT were determined according to the diagnostic criteria of NE, and the consistency between CBCT and NE was evaluated. Results: The clinical study of 300 children patients found that compared with NE, CBCT had a sensitivity of 87.3%, specificity of 89.2%, the positive predictive value of 93.20%, the negative predictive value of 80.5%, the positive likelihood ratio of 8.08, the negative likelihood ratio of 0.14, and Kappa value of .748. Conclusion: CBCT is a reliable and accurate tool for the diagnosis of adenoid hypertrophy and can be used as an alternative examination method for children with contraindications or intolerance during NE. Level of Evidence: 4.

Clinical characteristics of vestibular evoked myogenic potentials in children with recurrent vertigo of childhood.

OBJECTIVE: To explore the possible pathogenesis of recurrent vertigo of childhood (RVC) and the clinical diagnosis value of vestibular-evoked myogenic potentials (VEMPs). METHODS: The clinical data of 19 children (5.95 ± 0.38 years) diagnosed with RVC and 17 normal children (5.35 ± 0.31 years) enrolled in the control (NC) group from April 2017 to February 2021 was collected and analyzed. All subjects were tested for both cervical VEMP (cVEMP) and ocular VEMP (oVEMP). The elicit rate, thresholds, N1 latency, P1 latency, interval, amplitude, and amplitude asymmetry ratio (AAR) of VEMPs were compared and analyzed between the two groups. RESULTS: (1) The elicit rates of cVEMP and oVEMP have no significant difference between the two groups (P > 0.05). (2) The thresholds of cVEMP and oVEMP in the RVC group were higher than that in the NC group (P < 0.05). (3) The N1 latency of cVEMP in the RVC group was longer than that in the NC group (P < 0.05). The P1 latency of cVEMP and latencies of oVEMP have no significant difference between the two groups (P > 0.05). (4) The interval of cVEMP in the RVC group was longer than that in the NC group (P < 0.05), while the interval of oVEMP has no significant difference between the two groups (P > 0.05). (5) The amplitude of cVEMP in the RVC group was higher than that in the NC group (P < 0.05), while the amplitude of oVEMP was similar in the two groups (P > 0.05). (6) The AAR values of oVEMP and cVEMP were similar in the two groups (P > 0.05). CONCLUSIONS: The elicit rates of VEMPs in children with RVC did not differ from that of normal children, but the thresholds were all increased, suggesting reduced sensitivity of the otolith organ and vestibular nerve conduction pathways. The P1 latency of cVEMP was normal in children with RVC, but N1 latency and interval of cVEMP were increased, we finally reached a conclusion that there might be potential impairment in the inferior vestibular nerve and the subsequent nerve conduction pathway in RVC.

DHI Increases the Proliferation and Migration of Schwann Cells Through the PI3K/AKT Pathway and the Expression of CXCL12 and GDNF to Promote Facial Nerve Function Repair.

The facial nerve is one of the vulnerable nerves in otolaryngology. Repair and recovery of facial nerve injury have a high priority in clinical practice. The proliferation and migration of Schwann cells are considered of great significance in the process of nerve injury repair. Danhong injection (DHI), as a common drug for cardiovascular and cerebrovascular diseases, has been fully certified in neuroprotection research, but its role in facial nerve injury is still not clear. Our study found that DHI can promote the proliferation and migration of RSC96 cells, a Schwann cell line, and this effect is related to the activation of the PI3K/AKT pathway. LY294002, an inhibitor of PI3K, inhibits the proliferation and migration of RSC96 cells. Further studies have found that DHI can also promote the expression of CXCL12 and GDNF at gene and protein levels, and CXCL12 is, while GDNF is not, PI3K/AKT pathway-dependent. Animal experiments also confirmed that DHI could promote CXCL12 and GDNF expression and promote facial nerve function recovery and myelin regeneration. In conclusion, our in vitro and in vivo experiments demonstrated that DHI could promote the proliferation and migration of Schwann cells through the PI3K/AKT pathway and increase the expression of CXCL12 and GDNF to promote facial nerve function repair.

Hearing Protection Outcomes of Analog Electrode Arrays Coated with Different Drug-Eluting Polymer Films Implanted into Guinea Pig Cochleae.

OBJECTIVE: To investigate the hearing protection outcomes of different drug-eluting analog electrode arrays implanted into guinea pig cochleae. METHODS: Sixty guinea pigs were randomly divided into a negative control group and five experimental groups implanted separately with blank (drug carrier), dexamethasone (DXM), aracytine (Ara-C), Ara-C+DXM, and nicotinamide adenine dinucleotide (NAD+) eluting analog electrode arrays. Micro CT was used to supervise the surgical procedure. Auditory brainstem response (ABR) thresholds of the guinea pigs were measured and analyzed. RESULTS AND CONCLUSIONS: Compared with the negative control, all other groups showed a significant increase in ABR threshold (p<0.001) after surgery. Among them, there was no obvious difference between the blank (0 vs 90 days: 59.70±10.57 vs 64.60±9.47 dB SPL) and the NAD+ group (0 vs 90 days: 59.90±9.87 vs 64.70±8.65 dB SPL). On the other hand, the ABR thresholds in the DXM (0 days: 58.10±10.73 dB SPL; 90 days: 51.70±9.07 dB SPL) and the Ara-C group (0 days: 59.00±10.05 dB SPL; 90 days: 51.60±8.48 dB SPL) decreased significantly compared with the former two groups (p<0.001). However, the Ara-C+DXM group showed no further benefit (p>0.05). In addition, a significantly higher survival rate of spiral ganglion neurons in cochleae was observed in the Ara-C and/or DXM groups.

[Research advances on umbilical cord blood derived mesenchymal stem cell in therapy of sensorineural hearing loss].

Sensorineural hearing loss（SNHL） is a difficult and hot issue in the field of otology. The effect of medications targeting the mechanism of SNHL are often unsatisfactory for hearing improvement. Hearing aids and cochlear implants are the mainstream treatment methods at present, but neither of them can reverse the pathological changes of affected inner ear. In recent years, mesenchymal stem cells transplantation has been confirmed by several animal studies and clinical trials to have great potential for clinical applications in restoring the structure of the inner ear and hearing improvement to some extent. In this review, we review the characteristics of umbilical cord blood derived mesenchymal stem cells（UCBMSCs）, the approaches of transplantation, the efficacy and mechanism of UCBMSCs in the treatment of SNHL, and the safety of clinical application, covering the existing problems and future prospects of this rising treatment.