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 explore the causal association between serum 25-hydroxyvitamin D[25(OH)D]and tic disorder(TD)based on two sample Mendelian randomization(TSMR)analysis.Methods Single nucleotide polymorphisms(SNP)associated with exposure and outcome were selected from the Genome-Wide Association Studies datasets of the publicly gene databases.Serum 25(OH)D was taken as the exposure factor and TD as the outcome factor.The inverse variance weighted(IVW)method was used as the main analysis method for data analysis and visualization.Results Forward Mendelian randomization(MR)analysis included 75 25(OH)D SNPs.IVW results showed no statistically significant difference in the effect of serum 25(OH)D levels on TD.In the reverse MR analysis involving 5 TD SNPs,the IVW results indicated no statistically significant impact of TD on serum 25(OH)D levels.All auxiliary method results demonstrated no causal association between TD and serum 25(OH)D levels(P＞0.05).Conclusion Through the analysis of TSMR,the results showed that there was no direct causal relationship between serum 25(OH)D level and TD,and 25(OH)D may affect TD through indirect action.

Objective To explore the causal association between serum 25-hydroxyvitamin D[25(OH)D]and tic disorder(TD)based on two sample Mendelian randomization(TSMR)analysis.Methods Single nucleotide polymorphisms(SNP)associated with exposure and outcome were selected from the Genome-Wide Association Studies datasets of the publicly gene databases.Serum 25(OH)D was taken as the exposure factor and TD as the outcome factor.The inverse variance weighted(IVW)method was used as the main analysis method for data analysis and visualization.Results Forward Mendelian randomization(MR)analysis included 75 25(OH)D SNPs.IVW results showed no statistically significant difference in the effect of serum 25(OH)D levels on TD.In the reverse MR analysis involving 5 TD SNPs,the IVW results indicated no statistically significant impact of TD on serum 25(OH)D levels.All auxiliary method results demonstrated no causal association between TD and serum 25(OH)D levels(P＞0.05).Conclusion Through the analysis of TSMR,the results showed that there was no direct causal relationship between serum 25(OH)D level and TD,and 25(OH)D may affect TD through indirect action.

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 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 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.

This article reports a case of sinus node dysfunction induced by thalidomide in ulcerative colitis in the Affiliated Hospital of Qingdao University and discusses the drug-induced arrhythmias induced by thalidomide.

This article reports a case of sinus node dysfunction induced by thalidomide in ulcerative colitis in the Affiliated Hospital of Qingdao University and discusses the drug-induced arrhythmias induced by thalidomide.

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 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*