Objectives: . The aim of this study was to explore the functional consequences of two common variants, p.V37I and c.299-300delAT, in the hearing loss-associated gene GJB2. Methods: . Connexin 26 expression and gap junctional permeability were studied in HEK 293T cells transfected with plasmids expressing GJB2 wild-type, p.V37I, or c.299-300delAT CX26 proteins tagged with fluorescent markers. Functional analyses of various GJB2 haplotypes were conducted to thoroughly evaluate alterations in ionic and small-molecule coupling. Results: . The p.V37I protein was localized at the plasma membrane, but it failed to effectively transport intercellular propidium iodide or Ca2+ efficiently, indicating an impairment in both biochemical and ionic coupling. The presence of GJB2 p.V37I seemed to increase the cells’ sensitivity to H2O2 treatment. In contrast, the known variant c.299-300delAT protein was not transported to the cell membrane and was unable to form gap junctions, remaining confined to the cytoplasm. Both ionic and biochemical coupling were defective in cells transfected with c.299-300delAT. Conclusion . The p.V37I and c.299-300delAT GJB2 mutations resulted in deficient gap junction-mediated coupling. Additionally, environmental factors could influence the functional outcomes of the GJB2 p.V37I mutation. These findings could pave the way for the development of molecular therapies targeting GJB2 mutations to treat hearing loss.

Objectives: . The aim of this study was to explore the functional consequences of two common variants, p.V37I and c.299-300delAT, in the hearing loss-associated gene GJB2. Methods: . Connexin 26 expression and gap junctional permeability were studied in HEK 293T cells transfected with plasmids expressing GJB2 wild-type, p.V37I, or c.299-300delAT CX26 proteins tagged with fluorescent markers. Functional analyses of various GJB2 haplotypes were conducted to thoroughly evaluate alterations in ionic and small-molecule coupling. Results: . The p.V37I protein was localized at the plasma membrane, but it failed to effectively transport intercellular propidium iodide or Ca2+ efficiently, indicating an impairment in both biochemical and ionic coupling. The presence of GJB2 p.V37I seemed to increase the cells’ sensitivity to H2O2 treatment. In contrast, the known variant c.299-300delAT protein was not transported to the cell membrane and was unable to form gap junctions, remaining confined to the cytoplasm. Both ionic and biochemical coupling were defective in cells transfected with c.299-300delAT. Conclusion . The p.V37I and c.299-300delAT GJB2 mutations resulted in deficient gap junction-mediated coupling. Additionally, environmental factors could influence the functional outcomes of the GJB2 p.V37I mutation. These findings could pave the way for the development of molecular therapies targeting GJB2 mutations to treat hearing loss.

Objectives: . The aim of this study was to explore the functional consequences of two common variants, p.V37I and c.299-300delAT, in the hearing loss-associated gene GJB2. Methods: . Connexin 26 expression and gap junctional permeability were studied in HEK 293T cells transfected with plasmids expressing GJB2 wild-type, p.V37I, or c.299-300delAT CX26 proteins tagged with fluorescent markers. Functional analyses of various GJB2 haplotypes were conducted to thoroughly evaluate alterations in ionic and small-molecule coupling. Results: . The p.V37I protein was localized at the plasma membrane, but it failed to effectively transport intercellular propidium iodide or Ca2+ efficiently, indicating an impairment in both biochemical and ionic coupling. The presence of GJB2 p.V37I seemed to increase the cells’ sensitivity to H2O2 treatment. In contrast, the known variant c.299-300delAT protein was not transported to the cell membrane and was unable to form gap junctions, remaining confined to the cytoplasm. Both ionic and biochemical coupling were defective in cells transfected with c.299-300delAT. Conclusion . The p.V37I and c.299-300delAT GJB2 mutations resulted in deficient gap junction-mediated coupling. Additionally, environmental factors could influence the functional outcomes of the GJB2 p.V37I mutation. These findings could pave the way for the development of molecular therapies targeting GJB2 mutations to treat hearing loss.

Objectives: . The aim of this study was to explore the functional consequences of two common variants, p.V37I and c.299-300delAT, in the hearing loss-associated gene GJB2. Methods: . Connexin 26 expression and gap junctional permeability were studied in HEK 293T cells transfected with plasmids expressing GJB2 wild-type, p.V37I, or c.299-300delAT CX26 proteins tagged with fluorescent markers. Functional analyses of various GJB2 haplotypes were conducted to thoroughly evaluate alterations in ionic and small-molecule coupling. Results: . The p.V37I protein was localized at the plasma membrane, but it failed to effectively transport intercellular propidium iodide or Ca2+ efficiently, indicating an impairment in both biochemical and ionic coupling. The presence of GJB2 p.V37I seemed to increase the cells’ sensitivity to H2O2 treatment. In contrast, the known variant c.299-300delAT protein was not transported to the cell membrane and was unable to form gap junctions, remaining confined to the cytoplasm. Both ionic and biochemical coupling were defective in cells transfected with c.299-300delAT. Conclusion . The p.V37I and c.299-300delAT GJB2 mutations resulted in deficient gap junction-mediated coupling. Additionally, environmental factors could influence the functional outcomes of the GJB2 p.V37I mutation. These findings could pave the way for the development of molecular therapies targeting GJB2 mutations to treat hearing loss.

Objective This study addresses the characters of magnetic resonance imaging (MRI) and clinical features,and curative effects in the screening of SSNHL due to inner-ear hemorrhage.Methods MRI and relevant audiometric test were given to 160 patients with SSNHL,who were hospitalized in the First Affiliated Hospital of Sun Yat-sen University from January 2011 to April 2013.The clinical features and curative effects of patients with high signals in the labyrinth on MRI were analyzed.Results MRI abnormities were found in 22 (13.8％) of the patients.Specifically,eight cases were considered for innerear hemorrhage.For the eight inner-ear hemorrhage cases,clinical features included the sudden onset of complete hearing loss,which worsened within several hours.Pure tone audiometry indicated profound sensorineural deafness.The prevalence of inner-ear hemorrhage was 5％ in SSNHL cases and 18.6％ in cases of profound sensorineural.MRI showed high signal intensity in the cochlear,semicircular canals or vestibule on unenhanced T1-weighted and fluid-attenuated inversion recovery images.The high signal intensity in the inner ear gradually degraded in six months.There was no improvement in hearing for the patients with inner-ear hemorrhage following symptomatic therapy.Conclusion SSNHL due to inner-ear hemorrhage is characterized by profound sensorineural deafness in all frequencies,and high signal intensity for the hemorrhagic inner ear on T1-weighted MRI,with poor prognosis.

Objective:To investigate the characteristics of cochleo-vestibular dysfunction in patients with profound sudden deafness, and the prognosis of inner ear hemorrhage.Methods:From January 2017 to December 2018, 92 inpatients with profound sudden sensorineural hearing loss were enrolled in the Department of Otorhinolaryngology, First Affiliated Hospital of Sun Yat-sen University. Our studied patients included 47 males and 45 females, aged 20-78 (39.3±6.1) years. According to the results of inner ear magnetic resonance imaging (MRI), the patients were divided into two groups: inner ear hemorrhage group and non-inner ear hemorrhage group. The clinical features, vestibular tests and audiological examination results during follow up were compared between the two groups. SPSS 22.0 software was used for statistical analysis.Results:The inner ear hemorrhage group consisted of 32 cases (34.8%, 32/92), all of whom complained of vertigo (100%, 32/32). Simultaneous vertigo attack and hearing loss occurred in 78.1% of this group (24/32). Neither semicircular canals function, nor cervical vestibular evoked myogenic potential (c-VEMP), nor ocular vestibular evoked myogenic potential (o-VEMP) in the affected side was normal (100%, 32/32). The rates of benign paroxysmal positional vertigo (BPPV) and disequilibrium were 37.5% (12/32) and 25.0% (8/32) respectively. Hearing improved in 28.1% (9/32) two weeks after treatment, and became stable at one month′s follow up. In 60 cases without inner ear hemorrhage, 58.3% of them (35/60) experienced vertigo, which occurred simultaneously with hearing loss in 21 patients (60%, 21/35). The abnormal rates of semicircular canals function, c-VEMP and o-VEMP were 71.6% (43/60), 78.3% (47/60) and 66.7% (40/60), respectively. The incidence of BPPV was 16.7% (10/60) and 8.3% (5/60) in cases with disequilibrium. Hearing improved in 58.3% (35/60) two week after treatment, and became stable at three months′ follow up. Significant difference was found in either vertigo rate, or simultaneous vertigo/hearing loss rate, or abnormal c-VEMP/o-VEMP rates, or accompanying BPPV, or disequilibrium rates between the two groups ( P<0.05 each). Moreover, we observed better hearing recovery in non-inner ear hemorrhage group in the two weeks, one month, three months and six months′ follow up, when compared with those in inner ear hemorrhage groups ( P<0.05 each). Conclusions:Inner ear hemorrhage is associated with more severe cochlea-vestibular lesion and poorer prognosis, in comparison to the non-inner ear hemorrhage,in patients with profound sudden sensorineural hearing loss.

Objective: To analyze the clinical features and possible pathogenesis of sudden deafenss and vertigo induced by inner ear hemorrhage. Methods: Clinical data of 30 patients with inner ear hemorrhage, from the first affiliated hospital of Sun Yat-sen university during Jan 2016 to May 2017, were retrospectively analyzed. Results: Vergito and profound deafness were seen in all patients. The duration of vertigo ranged from 24 hours to three days in 11 cases, three to 14 days in the remaining 19 cases. Simultaneous occurrence of vergito and deafenss were seen in 24 patients. Semicircular canal hypofunction and abnormal cervical vestibular evoked myogenic potentials(C-VEMP)/ocular vestibular evoked myogenic potentials(O-VEMP) were detected in all cases. Ten patients had benign paroxysmal positional vertigo(BPPV) simultaneously. Hearing recovered in 20% of the cohort posttreatment. Dizziness and balance disturbance disappeared 1 to 2 months after therapy in 16 cases. Long term (6 months) follow up revealed poor hearing outcome and vestibular rehabilitation. Conclusion Vestibular vertigo and profound sensorineural hearing loss, with unsatisfactory clinical prognosis, constituted the characters of inner ear hemorrhage-associated sudden deafness.

Objective     To analyze the effect of myocardial protection between modified Del Nido cardioplegia and St. Thomas Hospital Cardioplegia in adult patients with aortic valve and mitral valve replacement. Methods     From January 2014 to June 2016, 140 patients underwent aortic valve and mitral valve replacement in our hospital. According to different cardioplegia, the patients were divided into two groups including a modified Del Nido cardioplegia group (70 patients, 37 males, 33 females at mean age of 53.13±9.52 years) and a St. Thomas cardioplegia group (70 patients, 32 males, 38 females, at age of 50.71±9.29 years). We collected clinical data of the patients before operation (T1), 2 h after aortic unclamping (T2), 24 h after operation (T3) and 48 h after operation (T4). Indexes of muscle enzymes including blood center creatine kinase (CK), creatine kinase isoenzyme (CK-MB) concentration and liver function indexes including urea nitrogen (BUN), creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST) concentrations, and compared the postoperative and follow-up clinical data. Results     There was no statistical difference in age, weight, gender, ejection fraction baseline data between the two groups (P>0.05). All patients were successfully completed  combined valve replacement under cardiopulmonary bypass. The cardiopulmonary time was no statistical difference between the two groups (P>0.05). However, compared with St. Thomas cardioplegia group, modified Del Nido group was less in perfusion (1.19±0.39 vs. 2.99±0.75, P<0.001), shorter in aortic clamping time (P=0.003). No statistical difference was found in defibrillation rate after resuscitation between the two groups (P=0.779). Biochemical indicators were not statistically different at different time points between the two groups (P>0.05). Conclusion     Modified Del Nido cardioplegia has the same effect on myocardial protection with St. Thomas cardioplegia in adult patients. It reduces the frequency of reperfusion, and shortens the clamping time. There is no additional injury in the important organs such as liver, kidney. Modified Del Nido cardioplegia myocardial protection ability in adult heart valve surgery is feasible.