Mutation of IFNLR1, an interferon lambda receptor 1, is associated with autosomal-dominant non-syndromic hearing loss.

Background Hereditary sensorineural hearing loss is a genetically heterogeneous disorder. Objectives This study was designed to explore the genetic etiology of deafness in a large Chinese family with autosomal dominant, nonsyndromic, progressive sensorineural hearing loss (ADNSHL). Methods Whole exome sequencing and linkage analysis were performed to identify pathogenic mutation. Inner ear expression of Ifnlr1 was investigated by immunostaining in mice. ifnlr1 Morpholino knockdown Zebrafish were constructed to explore the deafness mechanism. Results We identified a cosegregating heterozygous missense mutation, c.296G>A (p.Arg99His) in the gene encoding interferon lambda receptor 1 (IFNLR1) - a protein that functions in the Jak/ STAT pathway- are associated with ADNSHL Morpholino knockdown of ifnlr1 leads to a significant decrease in hair cells and non-inflation of the swim bladder in late-stage zebrafish, which can be reversed by injection with normal Zebrafish ifnlr1 mRNA. Knockdown of ifnlr1 in zebrafish causes significant upregulation of cytokine receptor family member b4 (interleukin-10r2), jak1, tyrosine kinase 2, stat3, and stat5b in the Jak1/STAT3 pathway at the mRNA level. ConclusionIFNLR1 function is required in the auditory system and that IFNLR1 mutations are associated with ADNSHL. To the best of our knowledge, this is the first study implicating an interferon lambda receptor in auditory function.

Effect of Anterior Thoracoscopic Release Combined with the Posterior Correction Operation on the Pulmonary Function of Patients with Idiopathic Scoliosis.

BACKGROUND: Anterior thoracoscopic release combined with posterior correction is a common surgery to treat idiopathic scoliosis (IS). However, whether it has detrimental effects on pulmonary function is still unknown. AIM: The aim of the study is to evaluate the effect of anterior thoracoscopic release combined with posterior correction on the pulmonary function. Materials and Methods A retrospective study of 28 (12 male, 16 female) patients with IS undergoing anterior thoracoscopic release combined with posterior correction from 2009 to 2011 was performed. The radiographic and pulmonary function evaluations were performed preoperatively and at 24 months postoperatively. RESULTS: The average coronal Cobb angle was corrected from 88.36 ± 25.6 degrees to 49.8 ± 11.8 degrees, and average sagittal Cobb angle was corrected from 57.5 ± 17.2 degrees to 26.3 ± 4.7 degrees. The measured forced vital capacity (FVC) and total lung capacity (TLC) were significantly increased at 2 years postoperatively (3.21 ± 1.18 versus 2.47 ± 0.33; 4.32 ± 1.41 versus 3.68 ± 0.36; p < 0.01). However, no significant difference in the FVC% and TLC% was observed. The functional residual capacity percentage was 109.87 ± 14.87 preoperatively and increased to 118.56 ± 34.34 at 2 years postoperatively (p < 0.05). Both the measured residual volume (RV) and RV% were reduced postoperatively (p < 0.05). The maximum ventilatory volume percentage improved significantly (107.38 ± 39.22 versus 77.46 ± 12.37, p < 0.05). In addition, total airway resistance, inhaled airway resistance, and exhaled airway resistance were all decreased significantly. CONCLUSION: Anterior thoracoscopic release combined with posterior correction has proved to be a safe surgical technique that results in minor pulmonary function impairment.

Comparison of the sagittal profiles among thoracic idiopathic scoliosis patients with different Cobb angles and growth potentials.

BACKGROUND: Previous studies have demonstrated that pelvic incidence and sacral slope are significantly greater in idiopathic scoliosis patients compared with normal adolescents. However, whether these sagittal parameters are related to the progression of scoliosis remain unknown. The present was designed to determine the differences in the sagittal profiles among thoracic idiopathic scoliosis patients with different potentials for curve progression. METHODS: Ninety-seven outpatient idiopathic scoliosis patients enrolled from June 2008 to June 2011 were divided to three groups according to different Cobb angles and growth potentials: (1) non-progression of thoracic curve group, Risser sign of 5 and Cobb's angle < 40°; (2) moderate progression of thoracic curve group, Risser sign of 5 and Cobb's angle ≥ 40°; and (3) severe progression of thoracic curve group, Risser sign ≤ 3 and Cobb's angle ≥ 40°. All patients underwent whole spinal anteroposterior and lateral X-ray in standing position, and the sagittal parameters were measured, including thoracic kyphosis, lumbar lordosis, sacral slope, pelvic incidence, and pelvic tilt. RESULTS: The average thoracic scoliosis Cobb's angle in the non-progression group was significantly less than that in the moderate progression group (P < 0.01) and severe progression group (P < 0.01), but there was no statistical difference in the average thoracic scoliosis Cobb's angle between the severe progression group and moderate progression group. The average thoracic kyphosis angle in the severe progression group (9° ± 4°) was significantly smaller than that in the non-progression group (18° ± 6°, P < 0.01) and moderate progression group (14° ± 5°, P < 0.05). No statistical differences were present in the average lumbar lordosis, sacral slope, pelvic incidence, and pelvic tilt among the three groups. CONCLUSIONS: Thoracic hypokyphosis is strongly related with the curve progression in thoracic idiopathic scoliosis patients, but not pelvic sagittal profiles.

[Changes of hearing threshold and calcium/calmodulin in the cochlear nucleus cells of mice with cytomegalovirus intracranial infection].

OBJECTIVE: To explore the changes in the threshold of auditory brainstem response (ABR) and [Ca(2+)]I and calmodulin (CaM) in cochlear nucleus of newborn mice infected by murine cytomegalovirus (MCMV) in the brain. METHODS: Sixty-nine newborn mice were randomized into model group and control group. The model group (54 mice) was established by intracranial injection with MCMV viral suspension 20 l and the same volume of 0.9% sodium chloride was injected in the control group (15 mice). After 1 month, the ABR was tested in a sound-electric screen environment and the threshold was recorded. Then intracellular free calcium [Ca(2+)]i and the mRNA level of CaM in the cochlear nucleus were assayed by flow cytometry and RT-PCR. RESULTS: Compare to the control group [(64.0 ± 1.3) dBSPL], the threshold of ABR in the model group [(84.5 ± 2.7) dBSPL] was increased (F = 2.789,P = 0.000). Moreover, in the model group the intracellular free calcium [Ca(2+)]i and the mRNA level of CaM in the cochlear nucleus were increased (F = 1.290, P = 0.000; F = 4.252, P = 0.023), and the differences were statistically significant. CONCLUSIONS: The intracranial injection of MCMV can lead to abnormal changes in the threshold of ABR in mice, and the change of [Ca(2+) ]I/CaM in cochlear nucleus may be the important pathological basis of sensorineural hearing loss induced by MCMV infection.