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 investigate the trends in mortality and life loss of gastric cancer in Wenzhou City, Zhejiang Province from 2014 to 2023, so as to provide the evidence for formulating the prevention and control strategy for gastric cancer. Methods: The surveillance on causes of death data of permanent residents in Wenzhou City were collected through the Wenzhou Chronic Disease Monitoring and Management Information System from 2014 to 2023. The crude mortality of gastric cancer was calculated, and standardized by the data from the Sixth Chinese National Population Census in 2010. The life loss were measured using potential years of life lost (PYLL) and rate of potential years of life lost (PYLLR). The characteristics of mortality and life loss of gastric cancer in different genders and age groups were described. The trends in mortality and PYLLR of gastric cancer were analyzed using the average annual percent change (AAPC). Results: Totally 17 080 deaths were reported due to gastric cancer in Wenzhou City from 2014 to 2023, accounting for 12.58% and ranking third in the order of malignant tumor deaths. The crude mortality of gastric cancer was 20.73/105, and the standardized mortality was 15.22/105, showing decreasing trends (AAPC=-3.311%, -6.470%, both P<0.05). The crude mortality of gastric cancer was 29.22/105 in men and 11.61/105 in women, with standardized mortality rates of 20.81/105 and 8.74/105 (both P<0.05). The crude mortality of gastric cancer appeared a tendency towards a rise with increasing age (P<0.05), reaching the highest rate of 225.88/105 in the group aged 80 to <85 years. The PYLL and PYLLR of gastric cancer were 107 607.50 person-years and 1.37‰. The PYLLR appeared a tendency towards a decline from 2014 to 2023, with AAPC of -6.667% (P<0.05). Conclusions The mortality and PYLLR of gastric cancer in Wenzhou City appeared a tendency towards a decline from 2014 to 2023. Men and the elderly populations were the key groups for the prevention and treatment of gastric cancer.

Objective:To explore the trend of hearing changes in infants with GJB2 gene p.V37I mutation at different months. Methods:The subjects were 54 children（108 ears） with p.V37I homozygous or compound heterozygous mutation in GJB2 gene. All the subjects underwent auditory brainstem response, auditory steady-state response, acoustic immittance and other audiological tests. Children were divided into three groups according to their age, 26 cases in group A were ≤3 months old, 17 cases in group B were>3~≤6 months old, and 11 cases in group C were>6 months old. Statistical analysis was performed on the three groups of ABR response threshold, hearing degree, the ASSR average response threshold of four frequencies and the ASSR response thresholds for each frequency of 500, 1 000, 2 000 and 4 000 Hz. Results:Among the 54 cases, 35 were male and 19 were female, with an age rang of 2-27 months and a median age of 4 months. The ABR response threshold of the three groups were ranked from low to high as group A, group B and group C, and the difference was statistically significant（P<0.05）. The ABR response thresholds of the three groups were ranked from low to high as group A, group B, and group C. The comparison between groups showed that the ABR response thresholds of group C was higher than that of group A（P=0.006）. The proportion of confirmed hearing loss in the three groups was 34.61%, 50.00% and 63.64%, respectively, and the difference of hearing level among the three groups was statistically significant（P<0.05）. The comparison between groups showed that the difference between group A and group C was statistically significant（P=0.012）, normal hearing accounted for the highest proportion in group A（65.39%）, while mild hearing loss accounted for the highest proportion in group C（45.46%）. The ASSR average response thresholds of the four frequencies in the three groups were ranked from low to high as group A, group B and group C, and the difference is statistically significant（P<0.05）. The comparison between groups showed that response ASSR thresholds of group C was higher than that of group A（P=0.002）. Response thresholds of ASSR in each frequency in the three groups were all ranked from low to high as in group A, group B and group C, and the differences were statistically significant（P<0.05）. Compared with each other between groups, response ASSR thresholds of group C was higher than those of group A（P=0.003） and group B（P=0.015） at 500 Hz, while response ASSR thresholds of group C was higher than group A at 1 000 Hz（P=0.010） and 2 000 Hz（P<0.001）, and there was no statistical difference at 4 000 Hz. Conclusion:The incidence of hearing loss in GJB2 gene p.V37I mutation increased with age, and the degree of hearing loss increased, the hearing progression was mainly 500, 1 000 and 2 000 Hz suggesting regular follow-up and alert to hearing changes.
Humans ; Connexin 26 ; Male ; Female ; Infant ; Child, Preschool ; Mutation ; Evoked Potentials, Auditory, Brain Stem ; Connexins/genetics* ; Auditory Threshold ; Hearing/genetics* ; Hearing Loss/genetics*

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 systematically review the application and effectiveness of deep learning(DL)in diagnosis of mild cogni-tive impairment(MCI)among older adults.Methods PubMed,Web of Science,CNKI and Wanfang databases were searched for literatures related to the application of DL in MCI among older adults,from database inception to December,2024.A scoping review was conducted.The literature screening process followed the Scoping Review Report Specification list,and the quality assess-ment was conducted using the cross-sectional study quality evaluation tool developed by the Evidence-based Health Care Center.Results A total of eleven papers were included,from Italy,USA,South Korea,China,India and Switzerland,involving 11 829 elderly participants,publicated mainly between 2014 and 2024,reflecting the rapid development trend of the field in the last decade,which was in line with the timing of the development of DL technology.The quality scores of the included literatures were all six to seven.The types of studies were all cross-sectional studies with significant cross-disciplinary characteristics,mainly originating from the fields of clinical medicine,biology and neuroimaging.The literature data were mainly based on the Alzheimer's disease Neuroimaging Program database and integrated other data resources.In terms of data type,in addition to brain imaging data,one study based on text data was also included.In terms of models used,five of the studies were mainly based on convolutional neu-ral networks,and the rest used different DL modeling frameworks.The task types contained binary and triple classification.In terms of prediction results,the DL models constructed on multimodal data,such as brain imag-es,could be used to construct high-precision prediction models for MCI classification,and the models were all good,with accuracy more than 70%and AUC values more than 0.7.The diagnostic accuracy of some of the mod-els was more than 90%,and the model with the highest prediction accuracy was the one that used the Biceph-Net lightweight framework,with accuracy close to 100%,and the text analysis model based on Transformer made the AUC value of 0.846,which provided new ideas for the diagnosis of non-imaging data.Conclusion DL can not only provide strong support for the accurate identification of MCI in the elderly,but also provide auxiliary prediction tools for clinicians,which can help delay the progression of the disease and improve the prognosis of patients.

Objective: To investigate the trends in mortality and life loss due to falls among the elderly in Wenzhou City, Zhejiang Province, so as to provide the basis for formulating prevention and control measures for falls among the elderly. Methods: The data on fall-related deaths among the elderly aged 60 and above in Wenzhou City were collected through the Wenzhou Chronic Disease Monitoring and Management Information System from 2015 to 2023. The crude mortality was calculated and standardized using the data from the Sixth National Population Census in 2010. The life loss were measured using potential years of life lost (PYLL), average years of life lost (AYLL), and potential years of life lost rate (PYLLR). The trends in mortality and life loss among the elderly were analyzed using the annual percent change (APC) and average annual percent change (AAPC). Results: There were 11 378 deaths due to falls among the elderly in Wenzhou City from 2015 to 2023, with a crude mortality of 82.67/100 000 and a standardized mortality of 65.32/105, which appeared no significant changing trend (AAPC=3.401%、2.995%,both P>0.05). There was a tendency towards a rise from 2019 to 2023 (APC=12.592%、11.507%, both P<0.05). The majority of falls occurred at home, with 6 312 cases accounting for 55.48%. The primary types of fall-related deaths were slips, trips, and falls on the same level, with 8 541 cases representing 75.07%. The crude mortality and standardized mortality of falls in males were 76.63/105 and 60.86/105, which were lower than that in females at 88.72/100 000 and 70.33/100 000 (both P<0.05), and the trends were consistent with the overall population. The crude mortality of falls among the elderly increased with age (P<0.05). From 2015 to 2023, the crude mortality of falls among the elderly aged 60 to <65 years showed an upward trend (AAPC=4.860%, P<0.05), while no significant trend was observed in other age groups (all P>0.05). The PYLL was 5 123 person-years, the AYLL was 0.45 years per person, and the PYLLR was 0.37‰. From 2015 to 2023, PYLL showed an upward trend (AAPC=5.477%, P<0.05). The PYLL, AYLL, and PYLLR for males were 3.08 times, 3.48 times, and 2.67 times those of females, respectively. Conclusions From 2015 to 2023, the mortality of falls among the elderly in Wenzhou City had remained relatively stable. However, PYLL showed an upward trend. Males and older seniors were key groups for falls prevention. It is recommended to enhance health education and promote age-friendly home modifications to prevent falls among the elderly.

Objective: To investigate the association between overweight, obesity, central obesity and hypertension, so as to provide the basis for formulating targeted hypertension prevention and control strategies. Methods: Permanent residents aged ≥18 years were selected in Wenzhou City, Zhejiang Province from June 2023 to August 2024 by a multistage cluster random sampling method. Data on demographic information, lifestyle, height, weight, waist circumference (WC), blood pressure, and blood biochemical indicators were collected through questionnaire surveys, physical examinations, and laboratory tests. The prevalence of hypertension was calculated and standardized using the data of the Sixth National Population Census in 2010. Body mass index (BMI) was calculated to determine overweight and obesity, while WC was used to identify central obesity. The association between overweight, obesity, central obesity and hypertension were analyzed using multivariable logistic regression models. Results: A total of 38 593 residents were surveyed, including 19 481 (50.48%) males and 19 112 (49.52%) females. The median age was 46.00 (interquartile range, 26.00) years. The rates of overweight, obesity, and central obesity were 32.74% (12 634 individuals), 10.27% (3 963 individuals), and 27.87% (10 755 individuals), respectively. There were 11 813 cases of hypertension, with a prevalence and standardized prevalence of 30.61% and 24.41%, respectively. Multivariable logistic regression analysis showed that after adjusting for demographic information, lifestyle, diabetes and dyslipidemia, the likelihood of hypertension in the overweight and obesity groups was 1.927 (95%CI: 1.815-2.045) times and 3.724 (95%CI: 3.404-4.073) times that of the normal BMI group, respectively. The likelihood of hypertension in the central obesity group was 2.346 (95%CI: 2.214-2.486) times that of the normal WC group. The likelihood of hypertension in the central obesity only, overweight only, overweight with central obesity, obesity only and obesity with central obesity groups was 1.586 (95%CI: 1.391-1.809), 1.704 (95%CI: 1.582-1.835), 2.433 (95%CI: 2.254-2.626), 1.768 (95%CI: 1.424-2.194), and 4.466 (95%CI: 4.053-4.921) times that of the normal BMI and WC group, respectively. Conclusions Overweight, obesity and central obesity were all associated with hypertension among adult residents. The highest likelihood of hypertension was observed among adult residents with both general obesity and central obesity.

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 investigate the value of T helper 17 cells（Th17）/regulatory T cells（Treg）imbalance in the evaluation of intravenous immunoglobulin（IVIG）resistance in children with Kawasaki disease and Kobayashi score≤4.Methods:A total of 78 children with Kawasaki disease and Kobayashi score ≤ 4 admitted to Hunan Children's Hospital from January 2020 to December 2023 were prospectively selected as the study subjects，all of whom received IVIG treatment.In the acute phase，the proportion of Th17 cells and Treg cells was detected.Children were divided into IVIG sensitive group and IVIG resistance group based on their responsiveness to IVIG treatment.Baseline data of children with different IVIG treatment responsiveness，acute Th17 cell inflammatory factors [interleukin（IL）-17，IL-21，tumor necrosis factor-α（TNF-α）]，Treg cell inflammatory factors [IL-10，IL-35，transforming growth factor-β（TGF-β）] levels，and Th17/Treg values were compared.The correlation between Th17/Treg values and IVIG resistance in children with Kawasaki disease was analyzed using a restricted cubic spline model（RCS）.According to the threshold of correlation between Th17/Treg values obtained from RCS analysis and drug resistance in children，Th17/Treg was grouped，with a focus on analyzing the predictive value and clinical benefits of Th17/Treg values for IVIG resistance in children with Kawasaki disease.Results:Among the 78 children with Kawasaki disease，16 were resistant to IVIG treatment，accounting for 20.51%.The levels of C-reactive protein（CRP）,IL-17,and Th17/Treg in the acute phase of children in the IVIG resistance group were higher than those in the IVIG sensitive group，while the levels of IL-10 were lower than those in the IVIG sensitive group（ P<0.05）.RCS analysis showed that there was a non-linear dose-response relationship between IVIG resistance and acute Th17/Treg values in children with Kawasaki disease（ P<0.05）.When the acute Th17/Treg value was greater than 1.05，the risk of IVIG resistance in children with Kawasaki disease increased with the increase in indicator levels.The levels of CRP and IL-17 in the acute phase of children with Th17/Treg>1.05 were higher than those in the Th17/Treg < 1.05 group，while IL-10 levels were lower than those in the Th17/Treg<1.05 group.The proportion of children resistant to IVIG treatment was higher than that in the Th17/Treg<1.05 group（ P<0.05）.Multivariate Logistic regression analysis showed that CRP，IL-17，IL-10，and Th17/Treg were the influencing factors of IVIG resistance in children with Kawasaki disease（ P<0.05）.It was found through a nomogram that the C-index of the acute phase Th17/Treg values and their secretion of inflammatory factors in children with Kawasaki disease and Kobayashi score ≤ 4，as well as other major indicators，predicted the risk of IVIG resistance.The C-index was 0.975（95% CI 0.944-1.000），indicating good discrimination.When drawing the decision curve，it was found that compared to using each indicator separately，the Th17/Treg value and its secreted inflammatory factors in the acute phase assisted other major indicators in drawing the decision curve with a higher net benefit rate，with a maximum net benefit rate of 0.205. Conclusion:IVIG resistance in children with Kawasaki disease and Kobayashi score≤4 is related to Th17/Treg imbalance.When the Th17/Treg value in the acute phase of the disease is greater than 1.05，the risk of IVIG resistance is higher.The inflammatory factors IL-17 and IL-10 secreted by the two can assist other known indicators related to IVIG resistance in Kawasaki disease patients，improving the accuracy of predicting resistance risk.

Objective:To investigate the value of T helper 17 cells（Th17）/regulatory T cells（Treg）imbalance in the evaluation of intravenous immunoglobulin（IVIG）resistance in children with Kawasaki disease and Kobayashi score≤4.Methods:A total of 78 children with Kawasaki disease and Kobayashi score ≤ 4 admitted to Hunan Children's Hospital from January 2020 to December 2023 were prospectively selected as the study subjects，all of whom received IVIG treatment.In the acute phase，the proportion of Th17 cells and Treg cells was detected.Children were divided into IVIG sensitive group and IVIG resistance group based on their responsiveness to IVIG treatment.Baseline data of children with different IVIG treatment responsiveness，acute Th17 cell inflammatory factors [interleukin（IL）-17，IL-21，tumor necrosis factor-α（TNF-α）]，Treg cell inflammatory factors [IL-10，IL-35，transforming growth factor-β（TGF-β）] levels，and Th17/Treg values were compared.The correlation between Th17/Treg values and IVIG resistance in children with Kawasaki disease was analyzed using a restricted cubic spline model（RCS）.According to the threshold of correlation between Th17/Treg values obtained from RCS analysis and drug resistance in children，Th17/Treg was grouped，with a focus on analyzing the predictive value and clinical benefits of Th17/Treg values for IVIG resistance in children with Kawasaki disease.Results:Among the 78 children with Kawasaki disease，16 were resistant to IVIG treatment，accounting for 20.51%.The levels of C-reactive protein（CRP）,IL-17,and Th17/Treg in the acute phase of children in the IVIG resistance group were higher than those in the IVIG sensitive group，while the levels of IL-10 were lower than those in the IVIG sensitive group（ P<0.05）.RCS analysis showed that there was a non-linear dose-response relationship between IVIG resistance and acute Th17/Treg values in children with Kawasaki disease（ P<0.05）.When the acute Th17/Treg value was greater than 1.05，the risk of IVIG resistance in children with Kawasaki disease increased with the increase in indicator levels.The levels of CRP and IL-17 in the acute phase of children with Th17/Treg>1.05 were higher than those in the Th17/Treg < 1.05 group，while IL-10 levels were lower than those in the Th17/Treg<1.05 group.The proportion of children resistant to IVIG treatment was higher than that in the Th17/Treg<1.05 group（ P<0.05）.Multivariate Logistic regression analysis showed that CRP，IL-17，IL-10，and Th17/Treg were the influencing factors of IVIG resistance in children with Kawasaki disease（ P<0.05）.It was found through a nomogram that the C-index of the acute phase Th17/Treg values and their secretion of inflammatory factors in children with Kawasaki disease and Kobayashi score ≤ 4，as well as other major indicators，predicted the risk of IVIG resistance.The C-index was 0.975（95% CI 0.944-1.000），indicating good discrimination.When drawing the decision curve，it was found that compared to using each indicator separately，the Th17/Treg value and its secreted inflammatory factors in the acute phase assisted other major indicators in drawing the decision curve with a higher net benefit rate，with a maximum net benefit rate of 0.205. Conclusion:IVIG resistance in children with Kawasaki disease and Kobayashi score≤4 is related to Th17/Treg imbalance.When the Th17/Treg value in the acute phase of the disease is greater than 1.05，the risk of IVIG resistance is higher.The inflammatory factors IL-17 and IL-10 secreted by the two can assist other known indicators related to IVIG resistance in Kawasaki disease patients，improving the accuracy of predicting resistance risk.