Hearing loss is the most prevalent disabling disease. Cochlear implantation（CI） serves as the primary intervention for severe to profound hearing loss. This consensus systematically explores the value of genetic diagnosis in the pre-operative assessment and efficacy prognosis for CI. Drawing upon domestic and international research and clinical experience, it proposes an evidence-based medicine three-tiered prognostic classification system（Favorable, Marginal, Poor）. The consensus focuses on common hereditary non-syndromic hearing loss（such as that caused by mutations in genes like GJB2, SLC26A4, OTOF, LOXHD1） and syndromic hereditary hearing loss（such as Jervell & Lange-Nielsen syndrome and Waardenburg syndrome）, which are closely associated with congenital hearing loss, analyzing the impact of their pathological mechanisms on CI outcomes. The consensus provides recommendations based on multiple round of expert discussion and voting. It emphasizes that genetic diagnosis can optimize patient selection, predict prognosis, guide post-operative rehabilitation, offer stratified management strategies for patients with different genotypes, and advance the application of precision medicine in the field of CI.
Humans ; Cochlear Implantation ; Prognosis ; Hearing Loss/surgery* ; Consensus ; Connexin 26 ; Mutation ; Sulfate Transporters ; Connexins/genetics*

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective:To evaluate the efficacy and safety of nebulized inhalation of recombinant human interferon (IFN) α1b injection in the treatment of respiratory syncytial virus (RSV) associated lower respiratory tract infections (pneumonia and bronchiolitis) in children.Methods:A randomized, double-blind, parallel, placebo-controlled add-on design was used.Children with pneumonia or bronchiolitis aged 2 months to 5 years who tested positive for RSV antigen within 72 hours of onset from 30 clinical trial sites including Beijing Children′s Hospital, Capital Medical University between February 2021 and December 2022 were included in this study and randomly divided into 2 groups at a ratio of 1∶1 based on a stratified-block method.Both groups received basic treatments such as cough control, asthma relieving, expectorant treatment, fever reduction, oxygen therapy, etc.The experimental group received additional nebulized inhalation of IFN α1b injection at a dose of 2.0 μg/(kg·time), twice a day.The control group received nebulized inhalation of placebo twice a day.Clinical efficacy was evaluated based on indicators such as the duration of clinical symptoms and signs, and the Kaplan-Meier method was used to calculate the median and 95% CI of the duration of clinical symptoms and signs.The Log-rank test was used to compared data between groups.Safety was assessed through the incidence of adverse reactions and laboratory tests, and the Chi-square test was used to analyze the difference between groups. Results:There were 123 children in the experimental group and 122 children in the control group.The median durations of all the 5 clinical symptoms and signs [including shortness of breath, wheezing, dyspnea (visible retractions), decreased transcutaneous oxygen saturation, and abnormal mental state] in the experimental group after treatment were slightly shortened than those in the control group [2.7 d(95% CI: 1.9-3.0 d)] vs.[2.9 d(95% CI: 2.6-3.6 d), P=0.027].The improvement in dyspnea (retractions) was especially pronounced in the experimental group, with a relief rate of 50.0% (0, 100%) on the first day of administration[compared with 0 (0, 50.0%) in the control group ( Z=2.002, P=0.025)].The median duration of dyspnea in the experimental group was nearly 1 day shorter than that in the control group [1.0 d(95% CI: 0.7-1.7 d) vs.1.8 d(95% CI: 1.0-2.5 d), P=0.046].There were no significant difference in hospital stay [6.0(5.0, 8.0) d vs.6.5(5.0, 8.0) d, Z=0.675, P=0.500], oxygen therapy duration [32.0(14.0, 96.3) h vs.39.0 (24.0, 83.2) h, Z=0.094, P=0.925], the recovery rate from clinical symptoms during treatment [(105/106, 99.1%) vs.(96/101, 95.0%)], and recurrence rate [(0/106, 0) vs.(2/101, 2.0%)] between the 2 groups (all P>0.05).However, the above-mentioned four indicators in the experimental group showed a trend of clinical benefits.The quantitative virus detection results showed that the RSV viral load in both groups decreased after treatment compared to before treatment.After 2 days of treatment, the decline rate of RSV viral load from the baseline was 0.90 lg copies/(mL·d) in the experimental group and 0.25 lg copies/(mL·d)in the control group, with a statistically significant difference ( P<0.05).Furthermore, there was no statistically significant difference in the incidence of adverse reactions between the 2 groups ( P>0.05).Importantly, no drug-related serious adverse reactions occurred in both groups. Conclusions:The nebulized inhalation therapy of IFN α1b demonstrates efficacy and safety in treating pediatric RSV associated lower respiratory tract infections.It particularly offers outstanding clinical therapeutic value for severe children.

Objective To observe the inter-observer consistency of diameter of inferior vena cava(IVC)and IVC collapsibility index(IVCCI)measured and assessed with echocardiography and the correlations with right heart parameters in patients with right heart dysfunction.Methods Forty-seven patients with right heart dysfunction were prospectively recruited in observation group,while 50 adults with normal right heart function were taken as controls(control group).Parameters of the right heart were obtained with echocardiography,including the right ventricular fractional area change(FAC),the tricuspid annular plane systolic excursion(TAPSE),the myocardial performance index(MPI),the tricuspid annular systolic velocity(S')as well as early and late diastolic velocity(e',a')and e'/a' ratio,also the tricuspid valve orifice early and late diastolic velocities(E,A)and E/A ratio and E/e',the vena contracta width of tricuspid regurgitation(TR-VCW),the maximum velocity of tricuspid regurgitation(TR-Vmax),the pulmonary artery systolic pressure(PASP)and right atrial area(RAA).Besides,the maximal and minimal diameter of IVC(IVCDmax,IVCDmin)during the respiratory cycle were measured with two dimensional(2D)ultrasound and anatomical M-mode ultrasound,respectively,and the IVCCI were calculated.Then 20 subjects were randomly selected from each group,and IVC parameters were obtained.The basic data,right heart parameters and IVC parameters were compared between groups,intra-class correlation coefficient(ICC)between 2 sonographers of IVC parameters were calculated,and correlations between IVC parameters and right heart parameters were assessed.Results No significant differences of gender,age nor body mass index(BMI)was detected between groups(all P＞0.05).Compared with those in control group,MPI,e',e'/a',E,A,E/e',TR-VCW,TR-Vmax,PASP and RAA increased,whereas FAC,TAPSE,S'and a'decreased in observation group(all P＜0.05).The inter-observer consistencies were good for IVCDmax and IVCCI in observation group(ICC=0.787-0.971)and IVCDmax in the control group(ICC=0.971,0.964)obtained with 2D ultrasound and anatomical M-mode ultrasound,but poor for IVCCI in control group(ICC=0.169,0.456).Compared with those in control group,IVC parameters 2D-IVCDmax,2D-IVCDmin,M-IVCDmax and M-IVCDmin increased but 2D-IVCCI and M-IVCCI decreased in observation group(all P＜0.05).In control group,2D-IVCDmax was weakly negatively correlated with TAPSE and a'(r=-0.392,-0.364),weakly positively correlated with e'/a',E,E/A,TR-VCW and RAA(r=0.396,0.483,0.461,0.565,0.582),2D-IVCCI was weakly negatively correlated with TR-VCW and RAA(r=-0.386,-0.380),while M-IVCDmax was weakly negatively correlated with TAPSE(r=-0.384),and weakly positively correlated with e'/a',E,E/A,TR-VCW and RAA(r=0.357,0.453,0.473,0.549,0.550),M-IVCCI was weakly negatively correlated with MPI,E,TR-VCW and RAA(r=-0.347,-0.337,-0.475,-0.421).Conclusion In patients with right heart dysfunction,IVCD diameter and IVCCI obtained with echocardiography had good inter-observer consistencies.Parameters obtained with 2D ultrasound and anatomic M-mode ultrasound had certain relations with the right heart parameters.

Objective:To explore the application value of non-invasive prenatal testing (NIPT) technology in twin pregnancy.Methods:A total of 339 twin pregnant women who underwent NIPT at Dalian Municipal Women and Children′s Medical Center(Group), Dalian Jinpu New District Maternity and Child Health Hospital, and Dalian Lvshunkou District People′s Hospital from July 1, 2019 to June 30, 2021 were continuously retrospectively included. The clinical characteristics and test results of pregnant women with high-risk and low-risk were analyzed.Results:Among 339 pregnant women, 336 were successfully tested, with a success rate of 99.12%(336/339); 6 pregnant women were at high risk of NIPT, with a positive screening rate of 1.77%(6/339), including 1 case of high risk of trisomy 13, 2 cases of high risk of trisomy 18, and 3 cases of high risk of Trisomy 21; the results of amniocentesis for 2 high-risk pregnant women were not abnormal.Conclusions:NIPT technology is non-invasive, safe and efficient, and is suitable for large-scale prenatal screening. However, the detection accuracy of pregnant women with twin pregnancy needs to be improved.

Objective:To investigate the relationship between the serum high mobility group box 1 (HMGB1) level and children with febrile convulsion(FC) and epileptic seizures in the future.Methods:A total of 359 children with first-episode FC occurring in January 2014 to January 2017 admitted to the Department of Pediatrics, Henan Provincial People′s Hospital, were enrolled in the FC group.One hundred children without FC were enrolled in the fever control group, and 100 healthy children were enrolled in the healthy control group.Children with FC were followed for 18 months and their seizures were recorded.Serum HMGB1 and inflammatory response indexes were measured in all subjects, and the diagnostic value of HMGB1 for FC was analyzed.Other data were used to analyze the correlation between HMGB1 and the conversion of FC into epilepsy.Results:The level of serum HMGB1 in the FC group were hig-her than those in the healthy control group and the fever control group, and the differences were statistically significant [(3.04±1.01) μg/L, (5.09±1.45) μg/L vs.(8.32±2.27) μg/L, all P<0.01]. serum HMGB1 level in children with FC was positively correlated with interleukin(IL)-1β, IL-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP) and white blood cell (WBC) ( r=0.364, 0.173, 0.227, 0.235, 0.247, all P<0.05). There were significant differences in HMGB1 levels between groups with different duration and types of convulsions [(8.11±2.15) μg/L vs.(10.19±2.51) μg/L, (7.63±1.93) μg/L vs.(9.83±2.25) μg/L, all P<0.05]; HMGB1 level diagnosis of FC was better [area under the receiver′s operating characteristic curve (AUC)=0.843 (95% CI: 0.811-0.873)]; Serum HMGB1 in children with epilepsy with FC was higher than that without conversion to epilepsy, and the difference was statistically significant [(8.18±2.14) μg/L vs.(8.95±2.73) μg/L, P<0.05]; However, its performance in predicting the conversion of FC to epilepsy was not high [AUC=0.596 (95% CI: 0.544-0.691)]; Multivariate regression analysis showed that it was not an independent influencing factor of FC to epilepsy [odd ratio( OR)=1.929, P=0.222]. Conclusions:Serum HMGB1 levels in children with FC are related to the onset, severity and type of fever, and are one of the influencing factors affecting the conversion of FC to epilepsy, but not the independent factors.

Objective To explore the therapeutic mechanism of in response to kainic acid－induced epilepsy in mice. Methods Sixty mice Were randomly divided into control group,model group and loW－dose Sirolimus group, medium－dose and high－dose Sirolimus groups. Prevention and therapeutic administration Were used in the Sirolimus loW,medium and high dose groups. One Week before model establishment,intraperitoneal injection of Sirolimus 1 mg／kg,3 mg／kg and 9 mg／kg Were given once a day,but the model group and the control group Were injected intra﹣peritoneally the same dose of 9 g／L saline. One Week after the preventive administration,all mice except the control group,Were intraperitoneally injected 30 mg／kg kainate solution,and the control group Was injected an equal dose of 9 g／L saline. Mice Were treated 1 Week after the establishment of the models. The number of mice With epileptic symp﹣toms and the number of epileptic seizures,the seizure time and the average number of episodes Were recorded,the Mor﹣ris Water maze test Was performed on the mice,and the arrival time,sWimming distance and number of crossing times of the mice Were collected. The expression levels of mTOR pathWay－related protein gene and the number of apoptotic cells in hippocampus Were detected in hippocampus of mice. Results Epilepsy symptoms appeared earlier in the model group after modeling,and the epileptoid－like symptoms Were significantly delayed in each group(P﹦0. 001 9). The epilepsy grading model group Was significantly higher than that of other groups. The mouse seizure time on the 6th day after modeling Was significantly higher than that on the 3rd day after modeling. The time required for the model epileptic mouse to reach the platform and the sWimming length Was significantly more than that of the control group( P ﹦0. 000 1),While the number of the mice traversing the platform Was significantly loWer(P﹦0. 000 2),and the admi﹣nistration group Was significantly relieved. The gene expression levels of mTOR pathWay key proteins mTOR and S6 in the hippocampus of mice in the model group Were significantly up－regulated(P﹦0. 000 1). Simultaneously,different doses of Sirolimus could significantly doWn － regulate PI3K,AKT,mTOR,and S6 gene expression levels( P ﹦0. 000 1). Compared With the control group,the gray ratios of p－PI3K,p－AKT,p－mTOR and p－S6 and normal PI3K,AKT,mTOR and S6 protein in the model group Were significantly higher(P﹦0. 000 1),and Sirolimus Was also observed. It Was significantly doWn－regulated after administration(P﹦0. 000 1). Conclusions Sirolimus can signifi﹣cantly inhibit the over－activation of mTOR signaling pathWay in the hippocampal region of kainic acid－induced epi﹣lepsy mice,thereby alleviating the symptoms of epilepsy in mice and increasing learning and memory.

Objective To assess the accuracy of automated image－based bilirubin ( AIB ) of newborns or early infants obtained using a smartphone application called BiliScan for Newborn Jaundice . Method Jaundiced neonates (gestational age≥35 weeks) and early infants (postnatal age≤60 days) from out－patient or in－patient of our hospital during November 2016 to September 2017 were prospectively included.The total serum bilirubin ( TSB ), transcutaneous bilirubin ( TcB ) and AIB on chest were completed simultaneously on hospitalization , pre phototherapy, 0 h and 12 ～24 h after cessation of phototherapy for in－patients, and after diagnosis of breast－feeding jaundice for out－patients participants.The AIB were all detected by smartphone with an application of BiliScan for Newborn Jaundice .Statistical analysis was performed by SPSS 20.0.Result A total of 296 sets of data were enrolled from 194 neonates or infants in this study.The accuracy of AIB was not inferior to the TcB (The difference between the mean of the absolute value of AIB －TSB and the absolute value of TcB －TSB was 0.77 mg/dl, 95% confidence interval were 0.63 ～0.91 mg/dl).These results of the subgroups from male and female term infants , postnatal age＞2 days and the value of TSB≤20 mg/dl were similar to the overall results.However, in the subgroup of TSB＞20 mg/dl, the accuracy of AIB was lower than that of TcB compared to TSB.There were good correlation (r＝0.824) and consistency (96.5% samples lay within the 95% limits of agreement ) between AIB and TSB.In the subgroup of 10 mg/dl ＜TSB≤20 mg/dl, the correlation and consistency between AIB and TSB were better than those of the subgroups of TSB ≤10 mg/dl and TSB ＞20 mg/dl. Furthermore, TSBs of 97.5% neonates were not beyond AIB plus 3.80 mg/dl.Conclusion When 10 mg/dl＜TSB≤20 mg/dl, the accuracy of AIB was not inferor to TcB , and the correlation and consistency between AIB and TSB were relatively superior.The application BiliScan for Newborn Jaundice was suitable for dynamic monitoring moderate jaundice of neonates and early infants at home.

Accurate determination of biological activity is essential in quality control of recombinant human brain natriuretic peptide (rhBNP). In previous study, we successfully developed a genetically modified cell line 293GCAC3-based ELISA assay for rhBNP. But ELISA procedure is still tedious, so this study was aimed to develop a rapid and simple bioassay for rhBNP using GloSensor technology, which provides a platform of flexible luciferase-based biosensors for real-time detection of signaling events in live cells, including cGMP production. A reporter cell line 293GCAGlo-G1 was constructed by transfecting pGloSensor?40 F plasmid into 293GCAC3. The reporter assay based on 293GCAGlo-G1 showed high precision with intra-assay CV being 8.3% and inter-assay CV being 14.1%; high accuracy with 80%, 100% and 120% recovery rate being 99.2%, 102.4% and 99.0% respectively; and great linearity with R2of linear fitting equation being 0.99. Besides, no significant difference was found in test results of reporter assay and 293GCAC3-based ELISA assay (paired t test, p＝0.630). All these results suggested that the reporter assay was a viable assay for biological determination of rhBNP.

Objective To investigate the effects of the interaction between human hepatoma cells and hepatic stellate cells on their growth state,and study its role of interaction on the progression of hepatocellular carcinoma.Methods Human hepatoma cell line HepG2 and hepatic stellate cell line hepatic stallate cells (HSC)-T6 were used and the methods including methyl thiazolyl tetrazolium (MTT) assay,flow cytometry (FCM) analysis,immunohistochemistry,and electron microscopy were employed in this experiment.The effects of conditioned medium (CM) of HepG2 on the activation and proliferation of HSC were explored.The effects of activated HSC CM on HepG2 proliferation were investigated.The uhrastructural changes of the two co-cultured cells were observed.Results MTT assay result showed that HepG2/HSC CM could promote HSC/HepG2 proliferation.FCM result demonstrated that HepG2/HSC CM could influence the cell cycle distribution in HSC/HepG2.Immunohistochemistry exhibited that after the treatment of HepG2/HSC CM,the expression ofα-smooth muscle actin (α-SMA) in HSC and proliferating cell nuclear antigen (PCNA) in HepG2 were increased.When HepG2 and HSC were co-cultured,the ultrastructure of HSC displayed an activated feature.Conclusions HepG2 cells can induce the activation and proliferation of HSC,and the activated HSC can also stimulate the proliferation of HepG2.Interaction between hepatoma cells and hepatic stellate cells may play an important role in the progression of hepatocellular carcinoma.