1.Clinical and genetic characteristics of children with neurodevelopmental disorder caused by MAPK8IP3 gene variations and literature review
Yanhong WANG ; Huichun ZHANG ; Yang GU ; Xuan ZHENG ; Xiaoman ZHANG ; Chao GAO ; Shiyue MEI ; Yaodong ZHANG
Chinese Journal of Neurology 2025;58(8):862-868
Objective:To summarize the clinical and genetic characteristics of patients with neurodevelopmental disorder with or without variable brain abnormalities (NEDBA) caused by MAPK8IP3 gene variation. Methods:The clinical data and genetic testing results of 2 children with NEDBA treated in Henan Children′s Hospital from August 2019 to January 2022 were collected retrospectively. Literature was searched and reviewed from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, PubMed database and OMIM database (up to October 2024) with" MAPK8IP3 gene ""NEDBA ""neurodevelopmental disorders "as the search terms. The main clinical genetic characteristics of NEDBA caused by MAPK8IP3 gene variation were summarized. Results:The 2 children, a boy aged 1 year and 8 months and a girl aged 1 year and 4 months, both showed global developmental delay and the onset of the disease in infancy. The de novo heterozygous mutation c.1732C>T(p.Arg578Cys) of the MAPK8IP3 gene was detected by whole-exome sequencing. Case 1 was followed up to 3 years and 10 months old, who had severe developmental delay and was accompanied by hip subluxation and strephexopodia. Literature search retrieved 0 Chinese literature and 2 English literatures. A total of 18 patients including 2 cases reported in this study were identified as NEDBA caused by MAPK8IP3 gene variations, including 16 cases with missense mutations and 2 cases with truncation mutations. Among them, 7 patients carried c.1732C>T(p.Arg578Cys) and 5 patients carried c.3436C>T(p.Arg1146Cys). The main clinical manifestations of the 18 patients included developmental delay/intellectual disability (18 cases), poor or absent speech (11 cases), abnormal neurological examination (10 cases: 6 with spastic paraplegia, 2 with spasticity, 2 with ataxia, 1 with unstable gait), hypotonia (10 cases), skeletal malformations (10 cases: 4 with short stature, 3 with scoliosis, 1 with 5th finger clinodactyly and brachydactylky, 1 with flat-valgus feet, 1 with hip subluxation), seizures (3 cases), left hearing loss (1 case), myopic astigmatism and pseudostrabismus (1 case), abnormal brain magnetic resonance imaging (15 cases). Conclusions:Patients with NEDBA is usually characterized by global developmental delay apparent from infancy or early childhood, resulting in language and motor disorders. Additional features may include hypotonia, spasticity, skeletal malformations and abnormal brain magnetic resonance imaging. Currently, missense variations are frequent among the heterozygous MAPK8IP3 genotypes, among which c.1732C>T(p.Arg578Cys) and c.3436C>T(p.Arg1146Cys) are considered hot spot variations.
2.Experience of LI Diangui in Treating Gastroesophageal Reflux Disease Based on the Theory of Turbidity-Toxin in Liver
Shiyue LIANG ; Mengqi GAO ; Yansheng LIU ; Minan BAI ; Yingying LOU ;
Journal of Traditional Chinese Medicine 2025;66(16):1640-1644
This paper summarized the clinical experience of Prof. LI Diangui in treating gastroesophageal reflux disease (GERD) based on the theory of turbidity-toxin in liver. It is believed that internal accumulation of turbidity-toxin and liver depression with stomach counterflow are the main pathogenesis of GERD, and thus the therapeutic methods of resolving turbidity and resolving toxins, regulating the liver and harmonizing the stomach are proposed. In clinical practice, GERD is divided into the early stage, middle stage and late stage. For the early stage, the modified Huazhuo Shugan Hewei Formula (化浊疏肝和胃方) is used to regulate qi and remove turbidity, soothe the liver and harmonize the stomach; for the middle stage, the modified Huazhuo Qingre Zhisuan Formula (化浊清热制酸方) is applied to clear heat, direct the turbid downward, and resolve toxins; for the late stage, the modified Yiwei Decoction (益胃汤) is adopted to replenish qi, nourish yin and simultaneously resolve turbidity-toxin. Throughout the treatment process, attention should be paid to protecting the spleen and stomach, and the medication could be modified according to changes of individual condition.
3.Clinical and genetic characteristics of children with neurodevelopmental disorder caused by MAPK8IP3 gene variations and literature review
Yanhong WANG ; Huichun ZHANG ; Yang GU ; Xuan ZHENG ; Xiaoman ZHANG ; Chao GAO ; Shiyue MEI ; Yaodong ZHANG
Chinese Journal of Neurology 2025;58(8):862-868
Objective:To summarize the clinical and genetic characteristics of patients with neurodevelopmental disorder with or without variable brain abnormalities (NEDBA) caused by MAPK8IP3 gene variation. Methods:The clinical data and genetic testing results of 2 children with NEDBA treated in Henan Children′s Hospital from August 2019 to January 2022 were collected retrospectively. Literature was searched and reviewed from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, PubMed database and OMIM database (up to October 2024) with" MAPK8IP3 gene ""NEDBA ""neurodevelopmental disorders "as the search terms. The main clinical genetic characteristics of NEDBA caused by MAPK8IP3 gene variation were summarized. Results:The 2 children, a boy aged 1 year and 8 months and a girl aged 1 year and 4 months, both showed global developmental delay and the onset of the disease in infancy. The de novo heterozygous mutation c.1732C>T(p.Arg578Cys) of the MAPK8IP3 gene was detected by whole-exome sequencing. Case 1 was followed up to 3 years and 10 months old, who had severe developmental delay and was accompanied by hip subluxation and strephexopodia. Literature search retrieved 0 Chinese literature and 2 English literatures. A total of 18 patients including 2 cases reported in this study were identified as NEDBA caused by MAPK8IP3 gene variations, including 16 cases with missense mutations and 2 cases with truncation mutations. Among them, 7 patients carried c.1732C>T(p.Arg578Cys) and 5 patients carried c.3436C>T(p.Arg1146Cys). The main clinical manifestations of the 18 patients included developmental delay/intellectual disability (18 cases), poor or absent speech (11 cases), abnormal neurological examination (10 cases: 6 with spastic paraplegia, 2 with spasticity, 2 with ataxia, 1 with unstable gait), hypotonia (10 cases), skeletal malformations (10 cases: 4 with short stature, 3 with scoliosis, 1 with 5th finger clinodactyly and brachydactylky, 1 with flat-valgus feet, 1 with hip subluxation), seizures (3 cases), left hearing loss (1 case), myopic astigmatism and pseudostrabismus (1 case), abnormal brain magnetic resonance imaging (15 cases). Conclusions:Patients with NEDBA is usually characterized by global developmental delay apparent from infancy or early childhood, resulting in language and motor disorders. Additional features may include hypotonia, spasticity, skeletal malformations and abnormal brain magnetic resonance imaging. Currently, missense variations are frequent among the heterozygous MAPK8IP3 genotypes, among which c.1732C>T(p.Arg578Cys) and c.3436C>T(p.Arg1146Cys) are considered hot spot variations.
4.Analysis of clinical characteristics and risk factors for delayed diagnosis of tuberculosis in children
Yilin WANG ; Qi SUN ; Zhuo QIAN ; Jingyue LI ; Shiyue MEI ; Hengmiao GAO ; Junwen YANG ; Zhipeng JIN
Chinese Journal of Infection and Chemotherapy 2024;24(5):507-514
Objective To summarize the clinical characteristics of delayed diagnosis of tuberculosis in children,analyze the risk factors of delayed diagnosis,and support early diagnosis of tuberculosis in children.Methods This is a retrospective analysis based on the clinical data of tuberculosis patients admitted to the Children's Hospital Affiliated to Zhengzhou University from January 2015 to February 2023.The clinical characteristics of children were analyzed in terms of age group.According to the definition of diagnosis delay,the patients were assigned to delayed group and non-delayed group.Univariate analysis and multivariate logistic regression were used to analyze the risk factors for diagnosis delay.Results A total of 82 children with tuberculosis were included(46 cases in delayed diagnosis group and 36 cases in non-delayed diagnosis group).The rate of diagnosis delay was 56.1%.The incidence of acute miliary pulmonary tuberculosis and tuberculous meningitis was significantly higher in children ≤5 years old than that in children>5 years old(P<0.05).Diagnosis delay was associated with significantly higher prevalence of chronic fever,cough>2 weeks,growth retardation and significantly longer duration of empirical antibiotic use compared to the children without diagnosis delay(P<0.05).Univariate analysis showed that patient origin,contact history,mixed infection,tuberculosis type,molecular biological assay and severe disease were related to the delay of TB diagnosis(P<0.05).Multivariate logistic regression analysis showed that patient origin[≥3 clinic visits(OR=7.064,95%CI:1.677-29.754)],mixed infection(OR=3.812,95%CI:1.185-12.260),severe disease(OR=3.697,95%CI:1.081-12.646)]were risk factors for diagnosis delay in children.Molecular biological assay(OR=4.642,95%CI:1.318-16.345)was a protective factor.Conclusions The clinical symptoms of tuberculosis in children are atypical.Delayed diagnosis of tuberculosis is common.Multiple clinic visits,mixed infection,and severe disease are the risk factors for diagnosis delay.Tuberculosis should be taken into account for the children with chronic fever,cough and growth retardation who have failed to respond to adequate therapy with third-generation cephalosporin and carbapenems.Molecular biological assay is helpful for early diagnosis of tuberculosis in children with negative sputum smear.
5.Analysis of clinical characteristics and risk factors for delayed diagnosis of tuberculosis in children
Yilin WANG ; Qi SUN ; Zhuo QIAN ; Jingyue LI ; Shiyue MEI ; Hengmiao GAO ; Junwen YANG ; Zhipeng JIN
Chinese Journal of Infection and Chemotherapy 2024;24(5):507-514
Objective To summarize the clinical characteristics of delayed diagnosis of tuberculosis in children,analyze the risk factors of delayed diagnosis,and support early diagnosis of tuberculosis in children.Methods This is a retrospective analysis based on the clinical data of tuberculosis patients admitted to the Children's Hospital Affiliated to Zhengzhou University from January 2015 to February 2023.The clinical characteristics of children were analyzed in terms of age group.According to the definition of diagnosis delay,the patients were assigned to delayed group and non-delayed group.Univariate analysis and multivariate logistic regression were used to analyze the risk factors for diagnosis delay.Results A total of 82 children with tuberculosis were included(46 cases in delayed diagnosis group and 36 cases in non-delayed diagnosis group).The rate of diagnosis delay was 56.1%.The incidence of acute miliary pulmonary tuberculosis and tuberculous meningitis was significantly higher in children ≤5 years old than that in children>5 years old(P<0.05).Diagnosis delay was associated with significantly higher prevalence of chronic fever,cough>2 weeks,growth retardation and significantly longer duration of empirical antibiotic use compared to the children without diagnosis delay(P<0.05).Univariate analysis showed that patient origin,contact history,mixed infection,tuberculosis type,molecular biological assay and severe disease were related to the delay of TB diagnosis(P<0.05).Multivariate logistic regression analysis showed that patient origin[≥3 clinic visits(OR=7.064,95%CI:1.677-29.754)],mixed infection(OR=3.812,95%CI:1.185-12.260),severe disease(OR=3.697,95%CI:1.081-12.646)]were risk factors for diagnosis delay in children.Molecular biological assay(OR=4.642,95%CI:1.318-16.345)was a protective factor.Conclusions The clinical symptoms of tuberculosis in children are atypical.Delayed diagnosis of tuberculosis is common.Multiple clinic visits,mixed infection,and severe disease are the risk factors for diagnosis delay.Tuberculosis should be taken into account for the children with chronic fever,cough and growth retardation who have failed to respond to adequate therapy with third-generation cephalosporin and carbapenems.Molecular biological assay is helpful for early diagnosis of tuberculosis in children with negative sputum smear.
6.Analysis of clinical characteristics and risk factors for delayed diagnosis of tuberculosis in children
Yilin WANG ; Qi SUN ; Zhuo QIAN ; Jingyue LI ; Shiyue MEI ; Hengmiao GAO ; Junwen YANG ; Zhipeng JIN
Chinese Journal of Infection and Chemotherapy 2024;24(5):507-514
Objective To summarize the clinical characteristics of delayed diagnosis of tuberculosis in children,analyze the risk factors of delayed diagnosis,and support early diagnosis of tuberculosis in children.Methods This is a retrospective analysis based on the clinical data of tuberculosis patients admitted to the Children's Hospital Affiliated to Zhengzhou University from January 2015 to February 2023.The clinical characteristics of children were analyzed in terms of age group.According to the definition of diagnosis delay,the patients were assigned to delayed group and non-delayed group.Univariate analysis and multivariate logistic regression were used to analyze the risk factors for diagnosis delay.Results A total of 82 children with tuberculosis were included(46 cases in delayed diagnosis group and 36 cases in non-delayed diagnosis group).The rate of diagnosis delay was 56.1%.The incidence of acute miliary pulmonary tuberculosis and tuberculous meningitis was significantly higher in children ≤5 years old than that in children>5 years old(P<0.05).Diagnosis delay was associated with significantly higher prevalence of chronic fever,cough>2 weeks,growth retardation and significantly longer duration of empirical antibiotic use compared to the children without diagnosis delay(P<0.05).Univariate analysis showed that patient origin,contact history,mixed infection,tuberculosis type,molecular biological assay and severe disease were related to the delay of TB diagnosis(P<0.05).Multivariate logistic regression analysis showed that patient origin[≥3 clinic visits(OR=7.064,95%CI:1.677-29.754)],mixed infection(OR=3.812,95%CI:1.185-12.260),severe disease(OR=3.697,95%CI:1.081-12.646)]were risk factors for diagnosis delay in children.Molecular biological assay(OR=4.642,95%CI:1.318-16.345)was a protective factor.Conclusions The clinical symptoms of tuberculosis in children are atypical.Delayed diagnosis of tuberculosis is common.Multiple clinic visits,mixed infection,and severe disease are the risk factors for diagnosis delay.Tuberculosis should be taken into account for the children with chronic fever,cough and growth retardation who have failed to respond to adequate therapy with third-generation cephalosporin and carbapenems.Molecular biological assay is helpful for early diagnosis of tuberculosis in children with negative sputum smear.
7.Establishment and Clinical Test of Automatic Image Recognition Model for Ulcerative Colitis Colonoscopy Based on ResNet
Yansheng LIU ; Qianru YU ; Kun ZHANG ; Weichao XU ; Minan BAI ; He HU ; Zhicheng WANG ; Shiyue LIANG ; Mengqi GAO ; Yingying LOU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(9):2346-2354
Objective To train an automatic recognition and classification model of ulcerative colitis colonoscopy image based on ResNet,and to test its accuracy,in order to help doctors improve the clinical detection rate and classification accuracy of ulcerative colitis.Methods A total of 4000 colonoscopy images were retrospectively collected from the Colonoscopy Center of Hebei Hospital of Traditional Chinese Medicine from January 2018 to October 2023,and were divided into normal group,mild group,moderate group and severe group according to Mayo endoscopic scoring criteria,with 1000 images for each group.After pre-processing such as brightness adjustment and Angle rotation,the number of images was expanded to 20,000,and the data set was randomly divided into training set,verification set and test set according to the ratio of 7∶2∶1.The training set and verification set are input into the ResNet model to learn and test its stability.After all training is completed,the accuracy of the model is recorded through the test set,and the accurate regression curve is made to evaluate the classification effect of the model.Results In the test set,the accuracy of classification of ulcerative colitis was 99.8%in normal group,98.8%in mild group,95.6%in moderate group and 97.8%in severe group.Conclusion ResNet has good performance in image recognition and classification of ulcerative colitis,can improve the clinical accuracy of ulcerative colitis,and can assist doctors to identify and classify the disease,which has a more reliable clinical application value.
8.Analysis of clinical characteristics and risk factors for delayed diagnosis of tuberculosis in children
Yilin WANG ; Qi SUN ; Zhuo QIAN ; Jingyue LI ; Shiyue MEI ; Hengmiao GAO ; Junwen YANG ; Zhipeng JIN
Chinese Journal of Infection and Chemotherapy 2024;24(5):507-514
Objective To summarize the clinical characteristics of delayed diagnosis of tuberculosis in children,analyze the risk factors of delayed diagnosis,and support early diagnosis of tuberculosis in children.Methods This is a retrospective analysis based on the clinical data of tuberculosis patients admitted to the Children's Hospital Affiliated to Zhengzhou University from January 2015 to February 2023.The clinical characteristics of children were analyzed in terms of age group.According to the definition of diagnosis delay,the patients were assigned to delayed group and non-delayed group.Univariate analysis and multivariate logistic regression were used to analyze the risk factors for diagnosis delay.Results A total of 82 children with tuberculosis were included(46 cases in delayed diagnosis group and 36 cases in non-delayed diagnosis group).The rate of diagnosis delay was 56.1%.The incidence of acute miliary pulmonary tuberculosis and tuberculous meningitis was significantly higher in children ≤5 years old than that in children>5 years old(P<0.05).Diagnosis delay was associated with significantly higher prevalence of chronic fever,cough>2 weeks,growth retardation and significantly longer duration of empirical antibiotic use compared to the children without diagnosis delay(P<0.05).Univariate analysis showed that patient origin,contact history,mixed infection,tuberculosis type,molecular biological assay and severe disease were related to the delay of TB diagnosis(P<0.05).Multivariate logistic regression analysis showed that patient origin[≥3 clinic visits(OR=7.064,95%CI:1.677-29.754)],mixed infection(OR=3.812,95%CI:1.185-12.260),severe disease(OR=3.697,95%CI:1.081-12.646)]were risk factors for diagnosis delay in children.Molecular biological assay(OR=4.642,95%CI:1.318-16.345)was a protective factor.Conclusions The clinical symptoms of tuberculosis in children are atypical.Delayed diagnosis of tuberculosis is common.Multiple clinic visits,mixed infection,and severe disease are the risk factors for diagnosis delay.Tuberculosis should be taken into account for the children with chronic fever,cough and growth retardation who have failed to respond to adequate therapy with third-generation cephalosporin and carbapenems.Molecular biological assay is helpful for early diagnosis of tuberculosis in children with negative sputum smear.
9.Analysis of clinical characteristics and risk factors for delayed diagnosis of tuberculosis in children
Yilin WANG ; Qi SUN ; Zhuo QIAN ; Jingyue LI ; Shiyue MEI ; Hengmiao GAO ; Junwen YANG ; Zhipeng JIN
Chinese Journal of Infection and Chemotherapy 2024;24(5):507-514
Objective To summarize the clinical characteristics of delayed diagnosis of tuberculosis in children,analyze the risk factors of delayed diagnosis,and support early diagnosis of tuberculosis in children.Methods This is a retrospective analysis based on the clinical data of tuberculosis patients admitted to the Children's Hospital Affiliated to Zhengzhou University from January 2015 to February 2023.The clinical characteristics of children were analyzed in terms of age group.According to the definition of diagnosis delay,the patients were assigned to delayed group and non-delayed group.Univariate analysis and multivariate logistic regression were used to analyze the risk factors for diagnosis delay.Results A total of 82 children with tuberculosis were included(46 cases in delayed diagnosis group and 36 cases in non-delayed diagnosis group).The rate of diagnosis delay was 56.1%.The incidence of acute miliary pulmonary tuberculosis and tuberculous meningitis was significantly higher in children ≤5 years old than that in children>5 years old(P<0.05).Diagnosis delay was associated with significantly higher prevalence of chronic fever,cough>2 weeks,growth retardation and significantly longer duration of empirical antibiotic use compared to the children without diagnosis delay(P<0.05).Univariate analysis showed that patient origin,contact history,mixed infection,tuberculosis type,molecular biological assay and severe disease were related to the delay of TB diagnosis(P<0.05).Multivariate logistic regression analysis showed that patient origin[≥3 clinic visits(OR=7.064,95%CI:1.677-29.754)],mixed infection(OR=3.812,95%CI:1.185-12.260),severe disease(OR=3.697,95%CI:1.081-12.646)]were risk factors for diagnosis delay in children.Molecular biological assay(OR=4.642,95%CI:1.318-16.345)was a protective factor.Conclusions The clinical symptoms of tuberculosis in children are atypical.Delayed diagnosis of tuberculosis is common.Multiple clinic visits,mixed infection,and severe disease are the risk factors for diagnosis delay.Tuberculosis should be taken into account for the children with chronic fever,cough and growth retardation who have failed to respond to adequate therapy with third-generation cephalosporin and carbapenems.Molecular biological assay is helpful for early diagnosis of tuberculosis in children with negative sputum smear.
10.Analysis of clinical characteristics and risk factors for delayed diagnosis of tuberculosis in children
Yilin WANG ; Qi SUN ; Zhuo QIAN ; Jingyue LI ; Shiyue MEI ; Hengmiao GAO ; Junwen YANG ; Zhipeng JIN
Chinese Journal of Infection and Chemotherapy 2024;24(5):507-514
Objective To summarize the clinical characteristics of delayed diagnosis of tuberculosis in children,analyze the risk factors of delayed diagnosis,and support early diagnosis of tuberculosis in children.Methods This is a retrospective analysis based on the clinical data of tuberculosis patients admitted to the Children's Hospital Affiliated to Zhengzhou University from January 2015 to February 2023.The clinical characteristics of children were analyzed in terms of age group.According to the definition of diagnosis delay,the patients were assigned to delayed group and non-delayed group.Univariate analysis and multivariate logistic regression were used to analyze the risk factors for diagnosis delay.Results A total of 82 children with tuberculosis were included(46 cases in delayed diagnosis group and 36 cases in non-delayed diagnosis group).The rate of diagnosis delay was 56.1%.The incidence of acute miliary pulmonary tuberculosis and tuberculous meningitis was significantly higher in children ≤5 years old than that in children>5 years old(P<0.05).Diagnosis delay was associated with significantly higher prevalence of chronic fever,cough>2 weeks,growth retardation and significantly longer duration of empirical antibiotic use compared to the children without diagnosis delay(P<0.05).Univariate analysis showed that patient origin,contact history,mixed infection,tuberculosis type,molecular biological assay and severe disease were related to the delay of TB diagnosis(P<0.05).Multivariate logistic regression analysis showed that patient origin[≥3 clinic visits(OR=7.064,95%CI:1.677-29.754)],mixed infection(OR=3.812,95%CI:1.185-12.260),severe disease(OR=3.697,95%CI:1.081-12.646)]were risk factors for diagnosis delay in children.Molecular biological assay(OR=4.642,95%CI:1.318-16.345)was a protective factor.Conclusions The clinical symptoms of tuberculosis in children are atypical.Delayed diagnosis of tuberculosis is common.Multiple clinic visits,mixed infection,and severe disease are the risk factors for diagnosis delay.Tuberculosis should be taken into account for the children with chronic fever,cough and growth retardation who have failed to respond to adequate therapy with third-generation cephalosporin and carbapenems.Molecular biological assay is helpful for early diagnosis of tuberculosis in children with negative sputum smear.

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