1.Study on the brain functional network and structural-functional coupling in children with drug-resistant epilepsy
Xuhong LI ; Jianhui XIAO ; Heng LIU ; Yulun HE ; Haifeng RAN ; Yuxin XIE ; Guiqin CHEN ; Qian′e YU ; Zhen ZENG ; Wenfu LI ; Tijiang ZHANG
Chinese Journal of Radiology 2025;59(2):184-191
Objective:To investigate the changes in brain functional network and structural-functional network coupling in children with drug-resistant epilepsy (DRE), and to analyze their correlation with cognitive function, disease duration, and age of onset.Methods:This study was a cross-sectional study. Clinical and imaging data of 19 children with DRE who received consultation and treatment at the Affiliated Hospital of Zunyi Medical University from August 2021 to August 2023 (DRE group) were prospectively included. Another 27 age-and sex-matched healthy children were collected as the healthy control group. All subjects had 3D-T 1WI, T 2 fluid-attenuated inversion recovery, diffusion tensor imaging (DTI), resting-state functional magnetic resonance imaging (rs-fMRI) scans and Wechsler Intelligence Scale assessments. Independent sample t-test and Mann-Whitney U test were used to analyze the global and local topological attributes, as well as the structural-functional coupling (SFC) values at the whole brain and modular levels in two groups. Correlations between abnormal resting state brain functional network indicators and the Wechsler Intelligence Scale score [verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), processing speed index (PSI), full scale intelligence quotient (FSIQ)], disease duration and age of onset was evaluated using a Spearman or Pearson correlation analysis. Results:Compared to the healthy control group, DRE group exhibited decreased VCI, PRI, WMI, PSI, FSIQ and the differences were all statistically significant (all P<0.05). Both brain functional networks had small world attributes. There was a statistically significant difference in the area under the curve of sparsity of degree centrality (DC) in the left pallidum between the DRE group and healthy control group (2.998±0.942, 4.992±1.945, t=-4.07, FDR corrected P<0.05). Compared with the control group, the DRE group had decreased SFC within the limbic network (LN) ( P<0.05), increased SFC within the sensorimotor (SMN) ( P<0.05), decreased SFC between the default mode network-LN ( P<0.05), and increased SFC between the SMN-attentional network (AN) ( P<0.05). There was no statistically significant difference in SFC at the whole brain level between the two groups. Correlation analysis indicated that DC in left pallidum in DRE group negatively correlated with the PSI ( r=-0.537, P=0.018), and SFC between the SMN and AN demonstrated a negative correlation with age of onset ( r=-0.537, P=0.018). Conclusion:The altered DC in left pallidum may be related to cognitive impairment in children with DRE, providing biomarker information for the study of neural mechanisms in children with DRE.
2.Analysis of risk factors for fever with thrombocytopenia syndrome-associated encephalitis
Jinqiu RAN ; Yuxin CHEN ; Chao WU
Chinese Journal of Clinical Laboratory Science 2025;43(8):596-601
Objective To analyze the risk factors for severe fever with thrombocytopenia syndrome(SFTS)-associated encephalitis and the risk factors for mortality in patients with SFTS-associated encephalitis.Methods The general data and laboratory indicators of 266 SFTS patients hospitalized at Nanjing Drum Tower Hospital from October 2010 to October 2022 were retrospectively collected.Logistic regression was used to analyze the risk factors for the occurrence of encephalitis in SFTS patients and the risk factors for the death of SFTS-related encephalitis patients,and a nomogram graph model was constructed to predict the risk of encephalitis in SFTS patients based on the results of multifactorial logistic regression analysis.Results Among the 266 SFTS patients included,84(31.6%)devel-oped encephalitis.Logistic regression analysis of general data and laboratory indicators indicated that age,gamma-glutamyl γ-transpep-tidase(GGT),and low levels of platelets(PLT)were the independent risk factors for the occurrence of encephalitis in SFTS patients.Among the 84 SFTS patients with encephalitis,47 cases(56.0%)died.Logistic regression analysis showed that activated partial thromboplastin time(APTT)was the independent risk factors for mortality in SFTS-related encephalitis patients.A nomogram model for predicting the occurrence of encephalitis in SFTS patients was constructed based on the above three independent risk factors.The area under the ROC curve(AUCROC)for the training and validation sets under the model was 0.755 and 0.778,respectively,suggesting good predictive performance.Conclusion Age,GGT,and low PLT levels were the independent risk factors for the occurrence of en-cephalitis in SFTS patients,and APTT was the independent risk factors for mortality in SFTS-related encephalitis patients.The nomo-gram model constructed based on the independent risk factors for the occurrence of encephalitis in the patients with SFTS demonstrated high predictive efficacy.
3.Single-cell sequencing reveals functional changes of dendritic cells in hepatitis B patients
Shixing CHEN ; Shengxia YIN ; Wanying ZHANG ; Juntao MA ; Hui CHEN ; Yijia ZHU ; Jinqiu RAN ; Yuxin CHEN ; Chao WU
Chinese Journal of Clinical Laboratory Science 2025;43(9):680-688
Objective To investigate the functional changes of dendritic cells(DCs)in patients at different stages of hepatitis B virus(HBV)infection and analyze the mechanisms underlying DC dysfunction.Methods Single-cell RNA sequencing dataset GSE182159 was downloaded from the GEO database and classified into healthy control(HC),immune active(IA),and immune tolerant(IT)groups based on infection stage.Peripheral blood samples were collected from 7 IA patients,7 IT patients,and 12 healthy controls.Flow cytometry was used to isolate classical dendritic cells(cDC)and plasmacytoid dendritic cells(pDC).The expression levels of transcription factors in cDC and pDC were measured by quantitative real-time PCR(qRT-PCR).Bioinformatics analyses were per-formed using R and Python package.Results The proportions of DCs in IA and IT groups were higher than that in HC group.Func-tional enrichment analysis revealed that the differentially expressed genes(DEGs)of cDCs in the IA group were primarily enriched for the processes,such as inflammatory response,MHC classⅡantigen processing and presentation,cell migration,signal transduction,metabolism,and immune response.In contrast the IT group exhibited lower enrichment intensity and a significant reduction in interfer-on responses.The DEGs of pDC in the IA group were enriched in the processes of MHC-Ⅱantigen presentation,Fc receptor signal transduction,and metabolism,whereas those in the IT group were showed enrichment only in Fc receptor signal transduction and me-tabolism with a lower intensity.Both groups exhibited reduced synthesis of typesⅠandⅡinterferons in pDC,with the IT group showing a more pronounced downregulation.Cell-cell communication analysis demonstrated enhanced interactions between myeloid cells(except pDC)and T cells in the IA group,whereas the interactions between cDC/pDC and T cells in the IT group were reduced.Transcription factor analysis revealed that STAT2,STAT3,IRF1,and IRF5 were highly expressed in the IA group but their expression exhibited low-er expression levels in the IT group.In contrast,BHLHE40 was broadly upregulated in both cDC and pDC subsets within the IT group.The qRT-PCR results were consistent with the findings from the single-cell transcription factor analysis.Conclusion The IT phase of hepatitis B infection represents a critical period for cDC dysfunction,characterized by significant suppression of MHCⅡantigen presen-tation,metabolism,and interferon responsiveness.The functional impairment of pDC precedes that of cDC,as evidenced by a marked downregulation of interferon synthesis capacity observed during the IA phase.
4.Analysis of risk factors for fever with thrombocytopenia syndrome-associated encephalitis
Jinqiu RAN ; Yuxin CHEN ; Chao WU
Chinese Journal of Clinical Laboratory Science 2025;43(8):596-601
Objective To analyze the risk factors for severe fever with thrombocytopenia syndrome(SFTS)-associated encephalitis and the risk factors for mortality in patients with SFTS-associated encephalitis.Methods The general data and laboratory indicators of 266 SFTS patients hospitalized at Nanjing Drum Tower Hospital from October 2010 to October 2022 were retrospectively collected.Logistic regression was used to analyze the risk factors for the occurrence of encephalitis in SFTS patients and the risk factors for the death of SFTS-related encephalitis patients,and a nomogram graph model was constructed to predict the risk of encephalitis in SFTS patients based on the results of multifactorial logistic regression analysis.Results Among the 266 SFTS patients included,84(31.6%)devel-oped encephalitis.Logistic regression analysis of general data and laboratory indicators indicated that age,gamma-glutamyl γ-transpep-tidase(GGT),and low levels of platelets(PLT)were the independent risk factors for the occurrence of encephalitis in SFTS patients.Among the 84 SFTS patients with encephalitis,47 cases(56.0%)died.Logistic regression analysis showed that activated partial thromboplastin time(APTT)was the independent risk factors for mortality in SFTS-related encephalitis patients.A nomogram model for predicting the occurrence of encephalitis in SFTS patients was constructed based on the above three independent risk factors.The area under the ROC curve(AUCROC)for the training and validation sets under the model was 0.755 and 0.778,respectively,suggesting good predictive performance.Conclusion Age,GGT,and low PLT levels were the independent risk factors for the occurrence of en-cephalitis in SFTS patients,and APTT was the independent risk factors for mortality in SFTS-related encephalitis patients.The nomo-gram model constructed based on the independent risk factors for the occurrence of encephalitis in the patients with SFTS demonstrated high predictive efficacy.
5.Single-cell sequencing reveals functional changes of dendritic cells in hepatitis B patients
Shixing CHEN ; Shengxia YIN ; Wanying ZHANG ; Juntao MA ; Hui CHEN ; Yijia ZHU ; Jinqiu RAN ; Yuxin CHEN ; Chao WU
Chinese Journal of Clinical Laboratory Science 2025;43(9):680-688
Objective To investigate the functional changes of dendritic cells(DCs)in patients at different stages of hepatitis B virus(HBV)infection and analyze the mechanisms underlying DC dysfunction.Methods Single-cell RNA sequencing dataset GSE182159 was downloaded from the GEO database and classified into healthy control(HC),immune active(IA),and immune tolerant(IT)groups based on infection stage.Peripheral blood samples were collected from 7 IA patients,7 IT patients,and 12 healthy controls.Flow cytometry was used to isolate classical dendritic cells(cDC)and plasmacytoid dendritic cells(pDC).The expression levels of transcription factors in cDC and pDC were measured by quantitative real-time PCR(qRT-PCR).Bioinformatics analyses were per-formed using R and Python package.Results The proportions of DCs in IA and IT groups were higher than that in HC group.Func-tional enrichment analysis revealed that the differentially expressed genes(DEGs)of cDCs in the IA group were primarily enriched for the processes,such as inflammatory response,MHC classⅡantigen processing and presentation,cell migration,signal transduction,metabolism,and immune response.In contrast the IT group exhibited lower enrichment intensity and a significant reduction in interfer-on responses.The DEGs of pDC in the IA group were enriched in the processes of MHC-Ⅱantigen presentation,Fc receptor signal transduction,and metabolism,whereas those in the IT group were showed enrichment only in Fc receptor signal transduction and me-tabolism with a lower intensity.Both groups exhibited reduced synthesis of typesⅠandⅡinterferons in pDC,with the IT group showing a more pronounced downregulation.Cell-cell communication analysis demonstrated enhanced interactions between myeloid cells(except pDC)and T cells in the IA group,whereas the interactions between cDC/pDC and T cells in the IT group were reduced.Transcription factor analysis revealed that STAT2,STAT3,IRF1,and IRF5 were highly expressed in the IA group but their expression exhibited low-er expression levels in the IT group.In contrast,BHLHE40 was broadly upregulated in both cDC and pDC subsets within the IT group.The qRT-PCR results were consistent with the findings from the single-cell transcription factor analysis.Conclusion The IT phase of hepatitis B infection represents a critical period for cDC dysfunction,characterized by significant suppression of MHCⅡantigen presen-tation,metabolism,and interferon responsiveness.The functional impairment of pDC precedes that of cDC,as evidenced by a marked downregulation of interferon synthesis capacity observed during the IA phase.
6.Study on the brain functional network and structural-functional coupling in children with drug-resistant epilepsy
Xuhong LI ; Jianhui XIAO ; Heng LIU ; Yulun HE ; Haifeng RAN ; Yuxin XIE ; Guiqin CHEN ; Qian′e YU ; Zhen ZENG ; Wenfu LI ; Tijiang ZHANG
Chinese Journal of Radiology 2025;59(2):184-191
Objective:To investigate the changes in brain functional network and structural-functional network coupling in children with drug-resistant epilepsy (DRE), and to analyze their correlation with cognitive function, disease duration, and age of onset.Methods:This study was a cross-sectional study. Clinical and imaging data of 19 children with DRE who received consultation and treatment at the Affiliated Hospital of Zunyi Medical University from August 2021 to August 2023 (DRE group) were prospectively included. Another 27 age-and sex-matched healthy children were collected as the healthy control group. All subjects had 3D-T 1WI, T 2 fluid-attenuated inversion recovery, diffusion tensor imaging (DTI), resting-state functional magnetic resonance imaging (rs-fMRI) scans and Wechsler Intelligence Scale assessments. Independent sample t-test and Mann-Whitney U test were used to analyze the global and local topological attributes, as well as the structural-functional coupling (SFC) values at the whole brain and modular levels in two groups. Correlations between abnormal resting state brain functional network indicators and the Wechsler Intelligence Scale score [verbal comprehension index (VCI), perceptual reasoning index (PRI), working memory index (WMI), processing speed index (PSI), full scale intelligence quotient (FSIQ)], disease duration and age of onset was evaluated using a Spearman or Pearson correlation analysis. Results:Compared to the healthy control group, DRE group exhibited decreased VCI, PRI, WMI, PSI, FSIQ and the differences were all statistically significant (all P<0.05). Both brain functional networks had small world attributes. There was a statistically significant difference in the area under the curve of sparsity of degree centrality (DC) in the left pallidum between the DRE group and healthy control group (2.998±0.942, 4.992±1.945, t=-4.07, FDR corrected P<0.05). Compared with the control group, the DRE group had decreased SFC within the limbic network (LN) ( P<0.05), increased SFC within the sensorimotor (SMN) ( P<0.05), decreased SFC between the default mode network-LN ( P<0.05), and increased SFC between the SMN-attentional network (AN) ( P<0.05). There was no statistically significant difference in SFC at the whole brain level between the two groups. Correlation analysis indicated that DC in left pallidum in DRE group negatively correlated with the PSI ( r=-0.537, P=0.018), and SFC between the SMN and AN demonstrated a negative correlation with age of onset ( r=-0.537, P=0.018). Conclusion:The altered DC in left pallidum may be related to cognitive impairment in children with DRE, providing biomarker information for the study of neural mechanisms in children with DRE.
7.Analysis of the epidemiological characteristics of adenovirus enteritis in hospitalized children in China from 2016 to 2021
Jiao TIAN ; Yuxin SHAO ; Xinyu WANG ; Qi LI ; Guoshuang FENG ; Yueping ZENG ; Ran WANG ; Zhengde XIE
Chinese Journal of Experimental and Clinical Virology 2024;38(6):687-693
Objective:This report analyzed the epidemiological characteristics of adenovirus enteritis in hospitalized children based on data from a nationwide multicenter study.Methods:We analyzed patient admission records of children hospitalized for adenoviral enteritis from the FUTang Update medical Records (FUTURE) database. Data were collected from 22 tertiary pediatric hospitals between January 2016 and December 2021. The study focused on identifying epidemiological trends and assessing the disease burden.Results:A total of 1 638 children were hospitalized for adenovirus gastroenteritis, accounting for 0.03% (1 638/5 465 249) of all hospitalizations in this age group and 2.88% (1 638/56 859) of diarrhea-related hospitalizations. The male-to-female ratio was 1.47∶1, with more males affected across all age groups, years, and regions. The majority of hospitalizations (77.41%) occurred among children aged 7 months to 2 years, who also represented the highest proportion (0.070%) of hospitalizations within their age group. Additionally, the number of hospitalizations increased annually from 2016 to 2021, with a noticeable rise in admissions during the summer and autumn months (July-October). Two-thirds of the patients had no significant extraintestinal comorbidities, while approximately one-fifth developed respiratory comorbidities such as pneumonia or acute bronchitis. The median length of hospital stay was 5 days (IQR 3.75-6), and the median hospitalization cost was 4 582.56 RMB (IQR 3 261.52-6 256.87).Conclusions:This study highlights adenovirus gastroenteritis as a significant cause of diarrhea-related hospitalizations in children in China, particularly among those aged 7 months to 2 years. Hospitalization rates were notably higher in males, with a peak in admissions during July to October. Most children experienced no extraintestinal comorbidities.
8.Analysis of acoustic characteristics in elderly patients with dysarthria in the anterior and posterior circulation cerebral infarction
Lu WANG ; Lei HE ; Shuangshuang CHAI ; Baoyu FENG ; Xiuying HUANG ; Yuxin TIAN ; Ran ZHANG ; Wen XU ; Lei GAO
Chinese Journal of Geriatrics 2024;43(12):1568-1574
Objective:To investigate the differences in acoustic characteristics between older patients with dysarthria resulting from anterior and posterior circulation cerebral infarctions.Methods:A case-control study was conducted.Sixty hospitalized older patients with dysarthria were selected and divided into two groups: the anterior circulation cerebral infarction group and the posterior circulation cerebral infarction group, each comprising 30 cases.Additionally, thirty healthy individuals aged 65 and above were included as a control group.The subjective evaluation of the patients' overall phonetic function was conducted using the GRBAS scale.Objective parameters, including fundamental frequency(F0), Jitter, Shimmer, maximum phonation time(MPT), maximum sound pressure level(SPLmax), minimum sound pressure level(SPLmin), and the dysphonia severity index(DSI), were collected using the DIVAS2.5 voice analysis system.We analyzed the acoustic characteristics across the three groups: patients with dysarthria and healthy subjects.Results:The grade(G), roughness(R), breathiness(B), asthenia(A), and strain(S)scores of patients in both the anterior and posterior circulation cerebral infarction groups were significantly higher than those of the healthy control group( F=16.574, 39.793, 46.309, 52.154, 25.603; all P<0.001).Furthermore, the roughness(R)and strain(S)of the voice in the anterior circulation cerebral infarction group were significantly elevated compared to the posterior circulation cerebral infarction group, whereas the breathiness(B), asthenia(A), and grade(G)scores in the posterior circulation cerebral infarction group were significantly higher than those in the anterior circulation cerebral infarction group(all P<0.001).The fundamental frequency value(F0)of the voice in patients with anterior circulation cerebral infarction was significantly greater than that of both the posterior circulation cerebral infarction group and the healthy control group( F=39.050, P<0.001).In contrast, the fundamental frequency value(F0)of patients with posterior circulation cerebral infarction was lower than that of the healthy control group( P=0.003).Additionally, the Jitter value in the anterior circulation cerebral infarction group was higher than in both the posterior circulation cerebral infarction group and the healthy control group( F=64.976, P<0.001).The Shimmer value in the anterior circulation cerebral infarction group was lower than that in the posterior circulation cerebral infarction group but higher than that in the healthy control group(both P<0.001).Finally, the values of MPT, SPLmin and SPL max, DSI in the anterior circulation cerebral infarction group were higher than those in the posterior circulation cerebral infarction group and lower than those in the healthy control group( F=90.406, 24.003, 16.164; all P<0.001); the value of DSI in the anterior circulation cerebral infarction group was lower than in both the posterior circulation cerebral infarction group and the healthy control group( F=87.921, P<0.001). Conclusions:There are notable differences in the acoustic characteristic parameters of dysarthria resulting from injuries at various anatomical sites in older patients with cerebral infarction.In practical clinical settings, a comprehensive evaluation of dysarthria in these patients should integrate the anatomical location of the injury, subjective symptom assessment, and objective analysis of acoustic characteristics to inform precise and personalized rehabilitation strategies.
9.Analysis of acoustic characteristics in elderly patients with dysarthria in the anterior and posterior circulation cerebral infarction
Lu WANG ; Lei HE ; Shuangshuang CHAI ; Baoyu FENG ; Xiuying HUANG ; Yuxin TIAN ; Ran ZHANG ; Wen XU ; Lei GAO
Chinese Journal of Geriatrics 2024;43(12):1568-1574
Objective:To investigate the differences in acoustic characteristics between older patients with dysarthria resulting from anterior and posterior circulation cerebral infarctions.Methods:A case-control study was conducted.Sixty hospitalized older patients with dysarthria were selected and divided into two groups: the anterior circulation cerebral infarction group and the posterior circulation cerebral infarction group, each comprising 30 cases.Additionally, thirty healthy individuals aged 65 and above were included as a control group.The subjective evaluation of the patients' overall phonetic function was conducted using the GRBAS scale.Objective parameters, including fundamental frequency(F0), Jitter, Shimmer, maximum phonation time(MPT), maximum sound pressure level(SPLmax), minimum sound pressure level(SPLmin), and the dysphonia severity index(DSI), were collected using the DIVAS2.5 voice analysis system.We analyzed the acoustic characteristics across the three groups: patients with dysarthria and healthy subjects.Results:The grade(G), roughness(R), breathiness(B), asthenia(A), and strain(S)scores of patients in both the anterior and posterior circulation cerebral infarction groups were significantly higher than those of the healthy control group( F=16.574, 39.793, 46.309, 52.154, 25.603; all P<0.001).Furthermore, the roughness(R)and strain(S)of the voice in the anterior circulation cerebral infarction group were significantly elevated compared to the posterior circulation cerebral infarction group, whereas the breathiness(B), asthenia(A), and grade(G)scores in the posterior circulation cerebral infarction group were significantly higher than those in the anterior circulation cerebral infarction group(all P<0.001).The fundamental frequency value(F0)of the voice in patients with anterior circulation cerebral infarction was significantly greater than that of both the posterior circulation cerebral infarction group and the healthy control group( F=39.050, P<0.001).In contrast, the fundamental frequency value(F0)of patients with posterior circulation cerebral infarction was lower than that of the healthy control group( P=0.003).Additionally, the Jitter value in the anterior circulation cerebral infarction group was higher than in both the posterior circulation cerebral infarction group and the healthy control group( F=64.976, P<0.001).The Shimmer value in the anterior circulation cerebral infarction group was lower than that in the posterior circulation cerebral infarction group but higher than that in the healthy control group(both P<0.001).Finally, the values of MPT, SPLmin and SPL max, DSI in the anterior circulation cerebral infarction group were higher than those in the posterior circulation cerebral infarction group and lower than those in the healthy control group( F=90.406, 24.003, 16.164; all P<0.001); the value of DSI in the anterior circulation cerebral infarction group was lower than in both the posterior circulation cerebral infarction group and the healthy control group( F=87.921, P<0.001). Conclusions:There are notable differences in the acoustic characteristic parameters of dysarthria resulting from injuries at various anatomical sites in older patients with cerebral infarction.In practical clinical settings, a comprehensive evaluation of dysarthria in these patients should integrate the anatomical location of the injury, subjective symptom assessment, and objective analysis of acoustic characteristics to inform precise and personalized rehabilitation strategies.
10.Analysis of the epidemiological characteristics of adenovirus enteritis in hospitalized children in China from 2016 to 2021
Jiao TIAN ; Yuxin SHAO ; Xinyu WANG ; Qi LI ; Guoshuang FENG ; Yueping ZENG ; Ran WANG ; Zhengde XIE
Chinese Journal of Experimental and Clinical Virology 2024;38(6):687-693
Objective:This report analyzed the epidemiological characteristics of adenovirus enteritis in hospitalized children based on data from a nationwide multicenter study.Methods:We analyzed patient admission records of children hospitalized for adenoviral enteritis from the FUTang Update medical Records (FUTURE) database. Data were collected from 22 tertiary pediatric hospitals between January 2016 and December 2021. The study focused on identifying epidemiological trends and assessing the disease burden.Results:A total of 1 638 children were hospitalized for adenovirus gastroenteritis, accounting for 0.03% (1 638/5 465 249) of all hospitalizations in this age group and 2.88% (1 638/56 859) of diarrhea-related hospitalizations. The male-to-female ratio was 1.47∶1, with more males affected across all age groups, years, and regions. The majority of hospitalizations (77.41%) occurred among children aged 7 months to 2 years, who also represented the highest proportion (0.070%) of hospitalizations within their age group. Additionally, the number of hospitalizations increased annually from 2016 to 2021, with a noticeable rise in admissions during the summer and autumn months (July-October). Two-thirds of the patients had no significant extraintestinal comorbidities, while approximately one-fifth developed respiratory comorbidities such as pneumonia or acute bronchitis. The median length of hospital stay was 5 days (IQR 3.75-6), and the median hospitalization cost was 4 582.56 RMB (IQR 3 261.52-6 256.87).Conclusions:This study highlights adenovirus gastroenteritis as a significant cause of diarrhea-related hospitalizations in children in China, particularly among those aged 7 months to 2 years. Hospitalization rates were notably higher in males, with a peak in admissions during July to October. Most children experienced no extraintestinal comorbidities.

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