To analyze the disease burden of acute lymphoid leukemia(ALL) and its changing trends in China and globally from 1990 to 2021, aiming to provide a theoretical basis for disease prevention, treatment, and policy formulation.

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

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.

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.

Objective To investigate the sequencing results of the SLC26A4 gene in 34 nuclear families and the genetic diagnosis on the offspring in the nuclear families who have been screened for SLC26A4 gene single-allele mutation in the deafness genetic screening,to provide a basis for genetic consulting.Methods A retrospective anal-ysis was performed on the results of SLC26A4 gene testing in 34 nuclear families,in which the offspring with SLC26A4 gene single-allele mutation in deafness genetic screening of each nuclear family.The offspring of 34 nucle-ar families with the second mutation site detected by sequencing,their audiological results were included in the anal-ysis;and if they suffered from hearing loss,the results of temporal bone CT or inner ear MRI were also included in the analysis.Results The sequencing results of 34 nuclear families showed that there were 23 offsprings(67.65％,23/34)with SLC26A4 gene single-allele mutation,and one parent was SLC26A4 gene single-allele mutation.There were 11 offsprings(32.35％,11/34)with second site,among which 7 offsprings(63.64％,7/11)with SLC26A4 gene complex heterozygous mutations,and their parents were SLC26A4 gene single-allele mutations.Among the 7 offsprings with SLC26A4 gene complex heterozygous mutation,3 cases were with hearing loss,all of which were diagnosed as large vestibular aqueduct syndrome,and the other 4 cases were normal.While 4 offsprings(36.36％,4/11)with SLC26A4 gene double heterozygous mutation(cis mutation),and one parent was SLC26A4 gene double heterozygous mutation.The hearing 4 offsprings with SLC26A4 gene double heterozygous mutations were normal.Among the 34 nuclear families,3 pairs of parents were SLC26A4 gene single-allele mutation,and both mutation sites were pathogenic,risk of reproducing children with hereditary hearing loss was 25％.Conclusion The detec-tion sites of deafness gene chip are limited.Using gene sequencing technology to sequence the nuclear family can fur-ther clarify the gene mutation type in offspring and provide guidance for parents to reproduce.

Objective To explore the effect of remote ischemic conditioning(RIC)combined with binaural beat music(BBM)train-ing in patients with cognitive dysfunction after cerebral infarction.Methods From June,2024 to January,2025,200 patients with cognitive dysfunction after cerebral infarction in the Affil-iated Hospital of North China University of Science and Technology were randomly divided into control group(n=50),RIC group(n=50),BBM group(n=50)and combined group(n=50).All the groups received stan-dardized routine training,RIC group received RIC,BBM group received BBM,and the combined group received RIC+BBM,for 14 days.They were assessed with Montreal Cognitive Assessment(MoCA)and Stroke-Specific Quality of Life Scale(SS-QOL)at baseline,day 14,and day 90.Results Two cases in the control group,four in RIC group,three in BBM group and three in the combined group dropped out.For MoCA scores,the inter-group effect,intra-group effect and interaction effect were all significant(F>13.463,P<0.001).After intervention,on both day 14 and day 90,the score of MoCA was higher in each in-tervention group than in the control group(P<0.05),and was higher in the combined group than in both BBM and RIC groups(P<0.05);and on day 90,it was higher in RIC group than in BBM group(P<0.05).For SS-QOL,the score increased with time in all the groups(χ2>75.182,P<0.001).After intervention,there was signif-icant difference at each time point among four groups(H>18.260,P<0.001).On day 14 and day 90,the score of SS-QOL was higher in the combined group than in the control and BBM groups(|Z|>3.149,P<0.05);on day 90,the score was higher in RIC group than in the control group(|Z|=3.590,P<0.05),and it was higher in the combined group than in RIC group(|Z|=3.186,P<0.05).Conclusion RIC,BBM and their combination all improved cognitive function after cerebral infarction.RIC was superior to BBM,and the combined intervention yielded the greatest benefit.Both RIC and the combined intervention im-proved quality of life,with the combined approach being the most effective.

Objective To explore the effect of remote ischemic conditioning(RIC)combined with binaural beat music(BBM)train-ing in patients with cognitive dysfunction after cerebral infarction.Methods From June,2024 to January,2025,200 patients with cognitive dysfunction after cerebral infarction in the Affil-iated Hospital of North China University of Science and Technology were randomly divided into control group(n=50),RIC group(n=50),BBM group(n=50)and combined group(n=50).All the groups received stan-dardized routine training,RIC group received RIC,BBM group received BBM,and the combined group received RIC+BBM,for 14 days.They were assessed with Montreal Cognitive Assessment(MoCA)and Stroke-Specific Quality of Life Scale(SS-QOL)at baseline,day 14,and day 90.Results Two cases in the control group,four in RIC group,three in BBM group and three in the combined group dropped out.For MoCA scores,the inter-group effect,intra-group effect and interaction effect were all significant(F>13.463,P<0.001).After intervention,on both day 14 and day 90,the score of MoCA was higher in each in-tervention group than in the control group(P<0.05),and was higher in the combined group than in both BBM and RIC groups(P<0.05);and on day 90,it was higher in RIC group than in BBM group(P<0.05).For SS-QOL,the score increased with time in all the groups(χ2>75.182,P<0.001).After intervention,there was signif-icant difference at each time point among four groups(H>18.260,P<0.001).On day 14 and day 90,the score of SS-QOL was higher in the combined group than in the control and BBM groups(|Z|>3.149,P<0.05);on day 90,the score was higher in RIC group than in the control group(|Z|=3.590,P<0.05),and it was higher in the combined group than in RIC group(|Z|=3.186,P<0.05).Conclusion RIC,BBM and their combination all improved cognitive function after cerebral infarction.RIC was superior to BBM,and the combined intervention yielded the greatest benefit.Both RIC and the combined intervention im-proved quality of life,with the combined approach being the most effective.

Objective To investigate the sequencing results of the SLC26A4 gene in 34 nuclear families and the genetic diagnosis on the offspring in the nuclear families who have been screened for SLC26A4 gene single-allele mutation in the deafness genetic screening,to provide a basis for genetic consulting.Methods A retrospective anal-ysis was performed on the results of SLC26A4 gene testing in 34 nuclear families,in which the offspring with SLC26A4 gene single-allele mutation in deafness genetic screening of each nuclear family.The offspring of 34 nucle-ar families with the second mutation site detected by sequencing,their audiological results were included in the anal-ysis;and if they suffered from hearing loss,the results of temporal bone CT or inner ear MRI were also included in the analysis.Results The sequencing results of 34 nuclear families showed that there were 23 offsprings(67.65％,23/34)with SLC26A4 gene single-allele mutation,and one parent was SLC26A4 gene single-allele mutation.There were 11 offsprings(32.35％,11/34)with second site,among which 7 offsprings(63.64％,7/11)with SLC26A4 gene complex heterozygous mutations,and their parents were SLC26A4 gene single-allele mutations.Among the 7 offsprings with SLC26A4 gene complex heterozygous mutation,3 cases were with hearing loss,all of which were diagnosed as large vestibular aqueduct syndrome,and the other 4 cases were normal.While 4 offsprings(36.36％,4/11)with SLC26A4 gene double heterozygous mutation(cis mutation),and one parent was SLC26A4 gene double heterozygous mutation.The hearing 4 offsprings with SLC26A4 gene double heterozygous mutations were normal.Among the 34 nuclear families,3 pairs of parents were SLC26A4 gene single-allele mutation,and both mutation sites were pathogenic,risk of reproducing children with hereditary hearing loss was 25％.Conclusion The detec-tion sites of deafness gene chip are limited.Using gene sequencing technology to sequence the nuclear family can fur-ther clarify the gene mutation type in offspring and provide guidance for parents to reproduce.

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.