Objective:To explore the hearing changes of children with different genotypes of SLC26A4 with enlarged vestibular aqueduct（EVA） using the linear mixed effect model（LMM）, providing evidence for the risk prediction of progressive hearing loss. Methods:A total of 48 children with EVA diagnosed in our hospital from January 2017 to January 2024. All subjects underwent two or more auditory tests. According to the results of deafness gene screening and sequencing, the genotypes are divided into: type A: homozygous mutation of c. 919-2A>G, type B: compound heterozygous or heterozygous mutation containing c. 919-2A>G, and type C: no mutation site of c. 919-2A>G of SLC26A4 gene. LMM was used to analyze the hearing thresholds change of 500 Hz, 1 000 Hz, 2 000 Hz, 4 000 Hz and the average in children with different genotypes with age. Results:A total of 92 ears, 314 audiograms of 48 children were included, the median number of audiograms was 3, the median age of initial diagnosis was 4 months, and the median follow-up time was 13 months. According to LMM, the standard deviation of random effects between patients and ears was large. There was no significant difference in hearing thresholds of different frequencies and the average in genotype A, genotype B, and genotype C, indicating that genotype had no effect on hearing threshold. There is an interaction between age and genotype. Taking genotype C as the reference, children with genotype B had the lowest increase in 500 Hz, 1000 Hz, and the average hearing threshold, followed by type A. Conclusion:EVA children exhibit substantial inter-individual/ear hearing threshold variability. Low-frequency thresholds progress slower than high frequencies. Genotype modulates progression rates, with wild-type（Type C） demonstrating fastest deterioration, supporting personalized auditory monitoring strategies.
Humans ; Vestibular Aqueduct/abnormalities* ; Genotype ; Sulfate Transporters ; Mutation ; Auditory Threshold ; Hearing Loss, Sensorineural/genetics* ; Male ; Female ; Child ; Child, Preschool ; Hearing Loss/genetics* ; Hearing Tests ; Linear Models ; Infant

OBJECTIVE To investigate the relationship between 23-site chip genetic screening failures and the results of newborns hearing screening,and to provide clinical reference for the diagnosis and treatment of genetic screening failures.METHODS There were 1 916 newborns born in the Beijing area from November 2022 to May 2024,who did not pass the 23-site chip genetic screening tests and underwent newborn hearing screening with definite initial screening results.Chi-square test was used to analyze the relationship between different mutation types and genotypes and the initial hearing screening results.RESULTS The overall neonatal hearing screening failure rate was 5.27%(101/1 916),with a higher failure rate of 61.54%(56/91)for homozygous and compound heterozygous mutations than the failure rate of 2.54%(45/1 772)for heterozygous mutations,0%(0/34)for digenic gene heterozygous mutations,and 0(0/19)for mtDNA 12S rRNA mutations,with a statistically significant difference(P<0.001).Among the homozygous and compound heterozygous mutations,the failure rates of homozygous and compound heterozygous for GJB2 gene and SLC26A4 gene were 59.76%(49/82)and 77.78%(7/9),respectively,with no statistically significant difference between the two groups(P=0.488).The homozygous and compound heterozygous for GJB2 gene were divided into three groups based on genotype:c.109G>A homozygous mutations,c.109G>A compound heterozygous mutations,and other homozygous and compound heterozygous mutations.The hearing screening failure rates of the three groups,from highest to lowest,were as follow:other homozygous and compound heterozygous mutations(88.89%,8/9),c.109G>A homozygous mutations(65.12%,28/43),and c.109G>A compound heterozygous mutations(43.33%,13/30),with a statistically significant difference(P=0.029).The failure rates of heterozygous for GJB2 gene,SLC26A4 gene and GJB3 gene were 2.86%(40/1 398),1.25%(4/321)and 1.89%(1/53),respectively,with no statistically significant difference among the three groups(P=0.241).The failure rate of hearing screening for individuals with GJB2 heterozygotes of different genotypes and individuals with SLC26A4 heterozygotes of different genotypes did not show statistically significant differences.CONCLUSION The failure rate of newborn hearing screening for homozygous and compound heterozygous mutation of 23-site chip genetic screening is higher than that of other mutation types,verifying the effectiveness of the newborn hearing screening program.Some newborns of homozygous and compound heterozygous mutation can pass the hearing screening,especially those with the c.109G>A homozygous and compound heterozygous mutation,who need clinical follow-up.

OBJECTIVE To explore the early detection of large vestibular aqueduct syndrome(LVAS)in children by applying several audiological indicators.METHODS Ninety-two children with hearing loss(aged 1-70 months)were enrolled and divided into an LVAS group(45 cases)and a control group(47 cases).Eleven audiological indicators were statistically analyzed:lateral of hearing loss,the degree of hearing loss,configuration of hearing loss;ABR air-conduction threshold;ABR air-bone gap;ASSR average threshold;ASSR thresholds at 0.5,1,2,and 4 kHz;and tympanogram type.Indicators showing significant two-group differences were used to construct a visualized multifactorial linear prediction model using the R language.RESULTS Nine indicators demonstrated statistically significant differences between groups(P<0.05):laterality,configuration of hearing loss,ABR air-conduction threshold,ASSR average threshold,ASSR thresholds at all frequencies(0.5,1,2,4 kHz),and tympanogram type.A prediction model was established.When the total model score ranged between 200 and 240 points,the predicted LVAS risk probability was 0.1 to 0.99.The consistency index(C-index)was 0.85,indicating good predictive ability of the model.CONCLUSION The identified nine audiological indicators are valuable for the early detection of LVAS in children.The developed model can estimate LVAS risk.After refinement,this model holds potential to support early clinical diagnosis and intervention.

To analyze the disease burden and trends of motor neuron disease(MND) in China and globally from 1990 to 2021, providing evidence for the formulation of relevant health strategies inChina.

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Objective:To conjecture the correlation between fetal hydrothorax(FHT)and pregnancy outcome through the analysis of 95 fetuses with hydrothorax and their mothers.Methods:In this case series study, 95 FHT patients admitted to the Third Affiliated Hospital of Zhengzhou University from January 2016 to October 2022 were retrospectively analyzed.According to the pregnancy outcome, these patients were divided into the induced labor group (13 patients) and the delivery group (82 patients). General data and genetic examinations of patients in the induced labor group were analyzed to explore their pathogenesis and genetics.According to the neonatal Apgar score, patients in the delivery group were divided into the normal group and the asphyxia group.Fifteen indicators including the maternal age, gestational week at first diagnosis, maternal complications, FHT location, FHT severity, FHT outcome during pregnancy, fetal ascites, hydrops fetalis, other abnormal fetal structures, amniotic fluid volume, intrauterine treatment, gestational week of delivery, mode of delivery, sex of the newborn, and newborn birth weight in the 2 groups were comparatively analyzed by the chi-square test.With the neonatal Apgar score as the dependent variable, variables that had statistical significance during the univariate analysis were included in the regression analysis, and a multivariate binary Logistic regression equation was established to explore the factors affecting the pregnancy outcome.Results:There were significant differences in the FHT outcome during pregnancy (16/22/13 cases vs.2/18/11 cases, χ2=6.994, P=0.030), FHT severity (27/24 cases vs.9/22 cases, χ2=4.475, P=0.034), hydrops fetalis (14/37 cases vs.23/8 cases, χ2=17.012, P=0.001), amniotic fluid volume (21/30 cases vs.24/7 cases, χ2=10.228, P=0.001), intrauterine treatment (19/32 cases vs.2/29 cases, χ2=9.603, P=0.002), gestational week of delivery[(38.15±2.05) weeks vs.(34.83±3.14) weeks, t=5.748, P=0.001], and newborn birth weight[(3 325.00±637.41) g vs.(2 714.58±837.99) g, t=3.727, P=0.001]between the normal and asphyxia groups(all P<0.05). Among them, hydrops fetalis ( OR=7.070, P=0.020) and severe FHT ( OR=6.927, P=0.043) were risk factors for neonatal Apgar scores.Intrauterine treatment ( OR=0.062, P=0.027) and gestational week of delivery( OR=0.577, P=0.022) could be used as a protective factor for neonatal Apgar scores. Conclusions:Diagnosis of FHT during the early gestational weeks and multiple fetal structural abnormalities, especially hydrops fetalis, have higher probabilities of abnormal genetic examinations, and the fetal prognosis was poor.It is recommended to carry out chromosomal karyo type and microarray tests, as well as whole exome sequencing and detection of genetic syndromes(if necessary), to avoid unnecessary fetal treatment and improve the survival rate of perinatal infants after intrauterine treatment.The poor prognosis is related to hydrops fetalis and severe FHT; however, timely intrauterine treatment and prolonging pregnancy can improve the pregnancy outcome and increase the survival rate of perinatal infants.

Objective To explore the application value of Fast Dixon technique in MR hip joint scanning.Methods Fifty young volunteers were recruited to perform axial and coronal MR scans of the hip joint.The scanning sequence was Fast Dixon T2WI sequence and conventional Dixon T2WI sequence.A double-blind five-point scale was used to subjectively evaluate the image quality of the two types sequences.The signal-to-noise ratio(SNR)and contrast-to-noise ratio(CNR)of the axial image were measured at the maximum level of the bladder display.Results In the scores of"good contrast between surrounding tissue and femoral head signal"and"overall image quality",the Fast Dixon T2WI sequence was better than the conventional Dixon T2WI sequence,and the difference was statistically significant(P<0.05).There was no significant difference in the average scores of"whether bladder artifacts affected the diagnosis"and"whether the fat suppression effect was good"between Fast Dixon T2WI sequence and conventional Dixon T2WI sequence(P>0.05).In the objective image quality evaluation,the SNR and CNR of Fast Dixon T2WI sequence were better than those of conventional Dixon T2WI sequence,and the difference was statistically significant(P<0.05).Conclusion The image quality score of the hip joint of young volunteers with Fast Dixon T2WI sequence combined with multiple averaging excitation technique is significantly higher than that of conventional Dixon T2WI sequence.The Fast Dixon T2WI sequence can increase the effect of inhibiting fat and motion artifacts without increasing the scanning time,and the joint face ratio is good.Fast Dixon technique can replace the traditional Dixon technique,thus becoming an optimal choice for hip joint MR scanning.

Objective To study the prognostic factors of progressive hearing loss among children with large vestibular aqueduct syndrome(LVAS).Methods The clinical data of 49 children(95 ears)with LVAS who re-ceived at least two hearing tests from January 2017 to January 2023 in our hospital were retrospectively analyzed,and they were divided into two groups according to the progression of hearing loss:the stable group(55 ears)and the progressive group(40 ears).The effects for progressive hearing loss of initial age,gender,laterality,imaging features,audiometric data,and incomplete partition type Ⅱ(IP-Ⅱ)and SLC26A4(type A,B,C,D)genotypes were analyzed by univariate and multivariate Cox regression analysis.The potential prognostic factors were further verified by Kaplan-Meier survival analysis.Results Each dB decrease in the initial average hearing threshold in-creased the expected hazard by 7.03％(P=0.02).Incomplete partition type Ⅱ(IP-Ⅱ)was associated with 5.11 hazard ratio(95％CI,1.81 to 14.45,P=0.002).Genotype C was associated with 6.13 hazard ratio for progressive hearing loss(95％CI,2.07 to 18.13,P=0.001).Conclusion The initial average hearing threshold,IP-Ⅱ,and SLC26A4 genotype C were significant effect factors of progressive hearing loss in patients with LVAS.This could predict the progression of hearing loss in children with LVAS and help identify patients at high risk for progressive hearing loss.

OBJECTIVE To analyze the difference of genotypes and hearing phenotypes in infants with biallelic allele variant in GJB2,and to provide reference for clinical practice. METHODS One hundred and forty-two subjects with biallelic allele variant in GJB2 were recruited in Beijing Tongren Hospital from August 2012 to March 2024. All subjects received universal newborn hearing screening(UNHS),neonatal deafness genetic screening and audiological tests. The subjects were divided into three groups according to the genotypes:T/T groups(truncated/truncated mutations,59 cases),T/NT group(truncated/non-truncated mutations,50 cases) and NT/NT group(non-truncated/non-truncated mutations,33 cases). Three groups of genotypes,newborn hearing screening results,age at first diagnosis and hearing diagnosis results were analyzed. RESULTS The homozygous mutation of c.235delC/c.235delC was the dominant in T/T group(57.63％),the compound heterozygous mutation of c.235delC/c.109G>A was the dominant in T/NT group(74.00％),and the homozygous mutation of c.109G>A/c.109G>A was the dominant in NT/NT group(96.97％). The overall refer rate of UNHS was 80.28％,and the refer rate of T/T group was 89.83％,which was significantly higher than that of T/NT group 70.00％(P=0.009). The age of first diagnosis of 142 cases was (3.70±1.56) months,there was no significant difference between the three groups(P>0.05). In 142 cases,104 cases with hearing loss accounted for 73.24％,38 cases with normal hearing accounted for 26.76％. The proportion of confirmed hearing loss in T/T group was 100.00％,which was significantly higher than that in T/NT group 52.00％(P<0.001) and NT/NT group 57.58％(P<0.001). In side of hearing loss,of the 104 patients with hearing loss,86 cases(82.69％) had bilateral hearing loss and 18 cases(17.31％) had unilateral hearing loss. The proportion of bilateral hearing loss in T/T group was 100.00％,which was significantly higher than that in T/NT group 57.69％(P<0.001) and NT/NT group 63.16％(P<0.001). Among 190 ears of 104 patients with hearing loss,the degree of hearing loss was predominantly mild to moderate(63.16％),followed by profound(24.74％) and severe(12.10％). Among them,the T/T group was mainly marked by severe to profound hearing loss(58.47％),while both the T/NT group and the NT/NT group were mainly characterized by mild hearing loss(58.54％ and 74.19％),and the differences among the three groups were statistically significant(P<0.001). CONCLUSION In the T/T group,all patients were diagnosed as bilateral hearing loss at first diagnosis,and was mainly severe and profound hearing loss. The bilateral and unilateral hearing loss were 52.00％ and 57.58％ in the T/NT group and NT/NT group at first diagnosis respectively,and was mainly mild hearing loss.

Objective:To observe the clinical efficacy and safety of Tongren Niuhuang Qingxin Pills combined with telmisartan tablets in the treatment of hypertensive vertigo syndrome of phlegm-heat disturbance.Methods:Randomized controlled trial was conducted. Totally 80 patients with hypertension vertigo and phlegm-heat disturbance syndrome were selected from March 2021 to August 2022 at Beijing Tongrentang Hospital of Traditional Chinese Medicine as the observation objects. They were randomly divided into two groups using a random number table method, with 40 cases in each group. The control group received oral telmisartan tablets, while the experimental group received Tongren Niuhuang Qingxin Pills in addition to the control group. Both groups were treated for 28 days and followed up for 1 month. The patients' room blood pressure before and after treatment was measured, and TCM syndrome scores were evaluated. The dizziness assessment rating scale (DARS) was used to evaluate the severity of dizziness, adverse reactions during treatment were recorded, drug safety was observed, and clinical efficacy was evaluated.Results:The total effective rate of the experimental group was 85.0% (34/40), and that of the control group was 7.5% (3/40), with statistical significance between the two groups ( χ2=48.32, P<0.001). Compared with before treatment, the experimental group had SBP [(136.63 ± 6.01) mmHg vs. (159.30 ± 9.01) mmHg, t=-21.00] and DBP [(84.48 ± 4.36) mmHg vs. (95.30 ± 3.75) mmHg, t=-13.80] after treatment; after treatment, SBP [(137.34 ± 6.39) mmHg vs. (158.00 ± 10.06) mmHg, t=-5.28] and DBP [(86.08 ± 4.43) mmHg vs. (95.18 ± 6.61) mmHg, t=-8.09] decreased in the control group ( P<0.01), but there was no statistical significance between the two groups after treatment ( P>0.05). After treatment, the TCM syndrome scores in the experimental group (8.68 ± 3.39 vs. 15.12 ± 3.03, Z=-6.61) were lower than those in the control group ( P<0.001), and DARS score [(8.53 ± 3.93) vs. (12.20 ± 3.95), Z=-3.63] was lower than that in the control group ( P<0.001). After treatment, the therapeutic effect index of TCM syndromes in the experimental group improved compared to before treatment in the same group. The therapeutic effect index of each symptom, from high to low, was as follows: rotation of oneself or visual objects>numbness of limbs>dry stool>dizziness and dizziness>liking cold drinks>bitter and dry mouth>red urine>red tongue, yellow coating, and greasy tongue>vomiting sticky and turbid phlegm>tinnitus>smooth pulse. There were no significant adverse reactions during the treatment of the two groups. Conclusion:Tongren Niuhuang Qingxin Pills combined with telmisartan can reduce the blood pressure of patients with hypertensive vertigo syndrome of phlegm-heat disturbance, improve the vertigo symptoms and TCM syndromes of patients, and the efficacy evaluation is superior to that of telmisartan alone.