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 analyze the clinical and epidemiological characteristics of adult carotid body tumors (CBTs) in Northwest China to provide references for early diagnosis and treatment of CBTs.Methods:A multicenter, retrospective, non-intervention epidemiological investigation was conducted on adult CBTs patients who were hospitalized from January 1, 2011 to June 30, 2023 in 7 Class A tertiary hospitals in Northwest China (Departments of Neurosurgery, First Affiliated Hospital of Air Force Medical University, Second Affiliated Hospital of Lanzhou University, People's Hospital of Gansu Province, 940 th Hospital of PLA Joint Logistic Support Force, People's Hospital of Qinghai Province, General Hospital of Ningxia Medical University, People's Hospital of Ningxia Hui Autonomous Region). Medical records were collected in these patients, and they were divided into 2 groups according to their average altitude residence: high altitude group (≥1 500 m) and low altitude group (<1 500 m); meanwhile, these patients were divided into Shamblin type I, type II and type III groups according to Shamblin classification criteria; differences in general data and clinical features among patients from different altitude groups or Shamblin subgroups were compared. Independent influencing factors for Shamblin type III CBTs were analyzed by multivariate ordered Logistic regression. Results:(1) A total of 359 patients were enrolled in the study, including 276 females and 83 males, aged (48.80±12.07) years; 211 patients were into the high altitude group and 148 into the low altitude group; 165 patients were into Shamblin type I group, 146 into Shamblin type II group, and 48 into Shamblin type III group. (2) Compared with those in the low altitude group, patients in the high altitude group had higher proportion of females, older age, lower proportion of Han nationality, higher proportion of Shamblin type I, smaller tumor volume, lower platelet count, higher red blood cell count, hematocrit, hemoglobin level, platelet distribution width and mean platelet volume, and higher large platelet percentage, with significant differences ( P<0.05). (3) Compared with those in the Shamblin type I group, patients in the Shamblin type III group had younger age, lower resident altitude, larger tumor volume, longer time interval from onset to diagnosis, higher proportion of unintentional tumor discovery, larger volume of intraoperative blood loss, lower hemoglobin level, hematocrit, mean erythrocyte volume, and mean hemoglobin concentration, decreased erythrocyte distribution width variable coefficient, and increased platelet count, with significant differences ( P<0.05). Compared with those in the Shamblin type II group, patients in Shamblin type III group had younger age, larger tumor volume, longer time interval from onset to diagnosis, larger volume of intraoperative blood loss, lower hemoglobin, hematocrit and mean erythrocyte volume, higher erythrocyte distribution width variable coefficient and platelet count, with significant differences ( P<0.05). (4) Age ( OR=0.960, 95% CI: 0.942-0.977, P<0.001), residence altitude ( OR=0.992, 95% CI: 0.990-0.999, P=0.020) and time interval from onset to diagnosis ( OR=1.009, 95% CI: 1.005-1.014, P<0.001) were independent influencing factors for Shamblin type III CBTs. Conclusions:More females than males are noted in patients with adult CBTs in Northwest China, and more CBTs patients live at high altitude, with Shamblin type I enjoying the highest proportion. More female and old patients lived at high altitude is noted than those lived at low altitude; patients with Shamblin type III have the youngest age, lowest altitude, and longest time interval from onset to diagnosis. CBTs patients with young age, low residence altitude, and long time interval from onset to diagnosis are more likely to develop Shamblin type III.

Objective:To explore the genetic etiology and clinical phenotype of Feingold syndrome due to chromosome 2p24.3p24.2 microdeletion.Methods:The clinical data of a child admitted to Henan Provincial People′s Hospital in November 2021 and diagnosed as Feingold syndrome type 1 (FGLDS1) associated with chromosome 2p24.3p24.2 microdeletion were collected. The clinical and genetic variation characteristics of the patient were summarized, and 10 patients with chromosome 2p microdeletion reported until November 2022 were reviewed.Results:The boy was 12 years and 5 months old. He presented with backward physical development, motor development retardation, low intelligence, special body and facial appearance, finger developmental deformity and other manifestations, accompanied by hyperactivity and aggressive behavior, impulsive irritability, self-injury and other behavior problems. The proband showed normal chromosome karyotype; the genome-wide copy number variant sequencing and trio-whole exome sequencing revealed a 2.61 Mb deletion at chromosome 2p24.3p24.2 region, and 10 genes including MYCN gene (exons 1 to 3) in the deleted region.The same deletion was not found in either of his parents. The genetic features of 11 cases (including this case) with chromosome 2p microdeletion were summarized, all of whom had insufficient haploid dosage of the MYCN gene due to chromosome 2p microdeletion, and the clinical manifestations of these 11 patients matched the clinical diagnosis of FGLDS1. Conclusion:The proband is consistent with the clinical presentation of the typical Feingold syndrome, and the haploinsufficiency of the MYCN gene due to the microdeletion of chromosome 2 is the genetic etiology of the proband.

Objective To study the effects of Gouteng Jiangya Jieyu Prescription(Uncariae Ramulus cum Uncis,Gastrodiae Rhizoma,Pheretima,Puerariae Lobatae Radix,Salviae Miltiorrhizae Radix et Rhizoma,etc.)on learning and memory ability,hippocampal inflammatory response and autophagy-related protein expression in rats with hypertension complicated with depression(HD).Methods Thirty spontaneously hypertensive rats(SHR)were randomly divided into model group,positive control group(Levamlodipine Besylate 0.45 mg·kg-1+Fluoxetine Hydrochloride 1.80 mg·kg-1)and Gouteng Jiangya Jieyu Prescription high-,medium-and low-dose groups(25.38,12.69,6.34 g·kg-1).Another 6 SD rats were used as blank control group.The SHR rats were intervened by chronic mild unpredictable stress combined with solitary rearing to replicate the HD rat model.At the same time,intragastric administration was given once a day for 6 weeks.The systolic blood pressure and diastolic blood pressure of rat tail artery were measured by non-invasive sphygmomanometer.The learning and memory ability of rats was detected by Morris water maze test.The ultrastructure of hippocampal neurons was observed by transmission electron microscope.The contents of interleukin-1β(IL-1β),IL-18 and IL-10 in hippocampus were detected by ELISA.The expression of autophagy-related proteins Beclin1 and Bcl-2 in hippocampus was detected by immunohistochemistry.The expression of autophagy-related proteins LC3Ⅰ and LC3Ⅱ in hippocampus was detected by Western Blot.Results Compared with the blank control group,the SBP and DBP of the rats in the model group were significantly increased from week 1-6(P＜0.01).The escape latency was significantly prolonged on the third and fourth day(P＜0.01).The first time of crossing the platform was significantly prolonged(P＜0.01),the times of crossing the platform area was significantly reduced(P＜0.05),and the retention time of the platform area was significantly shortened(P＜0.01).The neuronal cell body was obviously swollen,the ridge was destroyed,the nucleus was shrunk,and a large number of autophagosomes appeared;the contents of IL-1β and IL-18 in hippocampus were significantly increased(P＜0.01).The ratio of LC3Ⅱ/LC3Ⅰ protein expression and the expression of Beclin1 protein in hippocampus were significantly up-regulated(P＜0.05,P＜0.01),and the expression of Bcl-2 protein was significantly down-regulated(P＜0.01).Compared with the model group,the SBP of rats in the low-dose group of Gouteng Jiangya Jieyu Prescription was significantly decreased at the weeks 1,3,4,5,6(P＜0.01),and the DBP was significantly decreased at weeks 1,3,4,5(P＜0.05,P＜0.01).The SBP of the rats in the medium-dose group of Gouteng Jiangya Jieyu Prescription was significantly decreased at weeks 1,5,6(P＜0.01),and the DBP was significantly decreased at week 4(P＜0.05).The SBP of rats in the high-dose group of Gouteng Jiangya Jieyu Prescription was significantly decreased in the first week(P＜0.01).The escape latency of rats in the high-and medium-dose groups of Gouteng Jiangya Jieyu Prescription was significantly shortened on the third day(P＜0.05),and the escape latency of rats in the high-and low-dose groups of Gouteng Jiangya Jieyu Prescription was significantly shortened on the fourth day(P＜0.05).The first crossing platform time of rats in the high-,medium-and low-dose groups of Gouteng Jiangya Jieyu Prescription was significantly shortened(P＜0.01).The times of rats crossing the platform area in the medium-and low-dose groups of Gouteng Jiangya Jieyu Prescription were significantly increased(P＜0.05),and the retention time in the platform area was significantly prolonged(P＜0.05).In the administration group,the degree of hippocampal neuron damage was reduced,the nuclear shrinkage was significantly improved,and the autophagosomes were reduced.The contents of pro-inflammatory factors IL-1β and IL-18 in the hippocampus of rats in the high-and medium-dose groups of Gouteng Jiangya Jieyu Prescription were significantly decreased(P＜0.05,P＜0.01).The content of anti-inflammatory factor IL-10 in the hippocampus of rats in the high-dose group of Gouteng Jiangya Jieyu Prescription was significantly increased(P＜0.01).The protein expression ratio of LC3Ⅱ/LC3Ⅰ in hippocampus of high-,medium-and low-dose groups of Gouteng Jiangya Jieyu Prescription was significantly down-regulated(P＜0.01),and the expression of Bcl-2 protein was significantly up-regulated(P＜0.01).The expression of Beclin1 protein in the hippocampus of the high-and medium-dose groups of Gouteng Jiangya Jieyu Prescription was significantly down-regulated(P＜0.05,P＜0.01).Conclusion Gouteng Jiangya Jieyu Prescription can reduce the tail arterial pressure of HD rats,improve their learning and memory ability,and alleviate hippocampal neuronal damage.The mechanism may be related to reducing the release of inflammatory factors,increasing the level of anti-inflammatory factors,and regulating the expression of hippocampal autophagy-related proteins LC3Ⅱ/LC3Ⅰ,Beclin1 and Bcl-2.

OBJECTIVE: To identify pathogenic variants in two patients with suspected for Mowat-Wilson syndrome (MWS). METHODS: Genomic DNA was extracted from peripheral blood samples of the patients and his family members, and gene variants were analysis by Trio-whole exome sequences and copy number variation sequencing. RESULTS: Patient 1 was found to carried a de novo heterozygous c.2769C>A (p.Y923*) nonsense variant of ZEB2 gene. The variant was not found in his healthy parents and sister. Patient 2 carried a de novo heterozygous frameshift variant of the ZEB2 gene, namely c.315delC (p.A105Afs*3), which has not been previously reported. Both variants were predicted to be pathogenic and can lead to premature occurrence of stop codons. CONCLUSION The heterozygous c.2769C>A (p.Y923*) and c.315delC (p.A105Afs*3) variants of the ZEB2 gene probably underlay the pathogenesis in the two patients. Gene testing has facilitated confirmation of the diagnosis and genetic counselling.
DNA Copy Number Variations ; Facies ; Hirschsprung Disease ; Humans ; Intellectual Disability/genetics* ; Microcephaly/genetics* ; Zinc Finger E-box Binding Homeobox 2/genetics*

OBJECTIVE: To explore the clinical characteristics of a child with early-onset infantile epileptic encephalopathy type 8 associated with synonymous variant of ARHGEF9 gene. METHODS: Clinical data of the patient was summarized. The child and his parents were subjected to trio-whole exome sequencing. RESULTS: The child has presented with global developmental delay, epilepsy, impulsive behavior, hypersensitivity to sound, and mental retardation. He was found to harbor a de novo synonymous variant c.741C>T (p.Cys247Cys) of the ARHGEF9 gene. RNA splicing analysis confirmed that the variant has led to abnormal splicing of exon 5, resulting in a 55-bp deletion. CONCLUSION The clinical features of ARHGEF9 gene-related early-onset infantile epileptic encephalopathy type 8 includes mental and motor developmental delay, epilepsy, auditory allergy, and hyperactivity impulsivity. For synonymous variant, in vitro study and transcriptional experiment may be carried out to evaluate its functional and splicing effect. Above finding has enriched the phenotypic and genotypic spectrum of the ARHGEF9 gene.
Child ; Epilepsy/genetics* ; Exons ; Humans ; Infant ; Intellectual Disability/genetics* ; Male ; Rho Guanine Nucleotide Exchange Factors/genetics* ; Spasms, Infantile/genetics*

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.

Objective To explore the effect of Valpar occupational assessment training system on cognitive dysfunction in schizophrenia. Methods Sixty patients with schizophrenia were randomly assigned into Valpar therapy group ( experiment group, n=30) and traditional rehabilitation therapy group ( control group, n=30) according to the order number. The duration of the treatment was six weeks. The brief assess?ment of cognition in schizophrenia ( BACS) and Wisconsin card sorting test ( WCST) were conducted as pre?and post?treatment assessment. Results There were significant differences between scores of BASC in pre?and post?treatment assessment in experiment group. More specifically, the BASC scores in symbol coding (37.50±6.50, t=-4.60, P<0.01),token movement(60.80±8.72, t=-2.54, P=0.017),verbal memory (44.40±11.29, t=-2.19, P=0.037)),and word fluency(14.23±4.35, t=-3.39, P=0.002) were signifi?cantly different when comparing pre?and post?treatment assessment outcomes. In control group,the only sig?nificant difference was found in word fluency (14.23±4.35, t=-3.39, P=0.002).In addition,response errors (57.80±10.35, t=-3.06, P=0.005) and repeat errors (34.67±6.96, t=3.41, P=0.002) in WCST in exper?iment group were significantly different in pre?and post?treatment assessment while only repeat errors (34.30 ±7.01, t=4.36, P=0.000) was different in control group. It was further discovered that scores in in symbol cod?ing( t=2.010, P=0.048),token movement ( t=2.124, P=0.038),response errors ( t=2.413, P=0.020) and repeat errors( t=2.009, P=0.047) in WCST were different between two groups. Conclusion Valpar professional evaluation train?ing system can significantly improve the cognitive function of people with schizophrenia.