The clinical features and genetic variation of a patient with microcephaly, growth restriction, and increased sister chromatid exchange-2, who was treated in the Department of Gastroenterology, Children′s Hospital of Nanjing Medical University in April 2024 were analyzed, and the pathogenic cause was identified.The clinical data of the patient were collected, and the genomic DNA was extracted from the peripheral blood of the proband and his parents.Gene detection was conducted through whole-exome sequencing, and candidate variants were verified by Sanger sequencing and bioinformatics analysis.The proband presented with intrauterine growth restriction, retarded growth and development, microcephaly, and premature ageing-like facial features.Gene sequencing showed novel compound heterozygous variations c. 1333T>C (p.C445R) and c. 2345dup (p.P783Afs*3) in the proband.Both variants are conserved, and various bioinformatics tools predict them to be deleterious.The compound heterozygous variant (c.1333T>C/c.2345dup) in the TOP3A gene is the likely etiology of the patient′s condition.These two novel variants expand the spectrum of known TOP3A gene variants and provide a basis for genetic counseling for the family.

The clinical features and genetic variation of a patient with microcephaly, growth restriction, and increased sister chromatid exchange-2, who was treated in the Department of Gastroenterology, Children′s Hospital of Nanjing Medical University in April 2024 were analyzed, and the pathogenic cause was identified.The clinical data of the patient were collected, and the genomic DNA was extracted from the peripheral blood of the proband and his parents.Gene detection was conducted through whole-exome sequencing, and candidate variants were verified by Sanger sequencing and bioinformatics analysis.The proband presented with intrauterine growth restriction, retarded growth and development, microcephaly, and premature ageing-like facial features.Gene sequencing showed novel compound heterozygous variations c. 1333T>C (p.C445R) and c. 2345dup (p.P783Afs*3) in the proband.Both variants are conserved, and various bioinformatics tools predict them to be deleterious.The compound heterozygous variant (c.1333T>C/c.2345dup) in the TOP3A gene is the likely etiology of the patient′s condition.These two novel variants expand the spectrum of known TOP3A gene variants and provide a basis for genetic counseling for the family.

Objective:To explore the relevancy between the uridine diphosphate-glucuronylgly-cosyltransferase 1A1 (UGT1A1) gene mutation and the phenotype of indirect hyperbilirubinemia in children.Methods:Sixteen cases with indirect hyperbilirubinemia who visited the Department of Gastroenterology, Children's Hospital of Nanjing Medical University from July 2013 to November 2019 were retrospectively analyzed and were divided into Gilbert syndrome (GS), Crigler-Najjar syndrome type II (CNS-II), and indirect hyperbilirubinemia groups unexplained by UGT1A1 gene mutations. The differences in gene mutation site information and general clinical data were compared. The association between gene mutation spectrum and bilirubin level was explored by t-test analysis.Results:Ten of the sixteen cases with indirect hyperbilirubinemia had GS, three had CNS-II, and three had indirect hyperbilirubinemia unexplained by UGT1A1 gene mutations. A total of six mutation types were detected, of which c.211G?>?A accounted for 37.5% (6/16), c.1456T?>?G accounted for 62.5% (10/16), and TATA accounted for 37.5% (6/16), respectively. Compared with the GS group, the CNS group had early disease onset incidence, high serum total bilirubin ( t ?=?5.539, P ??0.05) and age of onset ( t ?=?0.3611, P ?>?0.05) between the two groups. There was no significant correlation between the number of UGT1A1 gene mutations and serum bilirubin levels. Children with c.1456T?>?G homozygous mutations had the highest serum bilirubin levels. Conclusion:The common pathogenic variants of the UGT1A1 gene sequence are c.1456T?>?G, c.211G?>?A, and TATA, indicating that these site mutations are related to the occurrence of indirect hyperbilirubinemia and have important guiding significance for the etiological analysis of indirect hyperbilirubinemia in children.

Objective To observe the value of quality control system based on artificial intelligence(AI)for improving imaging quality of chest CT.Methods Totally 1 726 CT images obtained from 415 patients were retrospectively collected,among which 1 414 images were used for convolutional neural network(CNN)training and the rest 312 images were used for validation.Precision,Recall,F1-Score,mean average precision(mAP)and intersection over union(IOU)of quality control system based on AI for chest CT scanning were calculated.Meanwhile,21 patients with unsatisfactory chest CT who would undergo re-examination were prospectively enrolled,and chest CT scanning with quality control system based on AI were performed.The results of 2 examinations were compared.Results Precision,Recall,F1-Score,mAP and IOU of quality control system based on AI for chest CT were all good.All 21 cases were diagnosed correctly with re-examination CT based on quality control system.Among 21 cases,the first CT misdiagnosed 19 cases,the displaying of the area,volume and display quality of pulmonary nodules were not significantly different,but the morphology,boundaries,spiny protrusions,vacuolar signs,inflatable bronchial signs of nodules as well as the thickened and twisted blood vessels were obviously different between 2 times examination.The first CT missed 1 case while correctly diagnosed 1 case.Conclusion The quality control system based on AI was helpful for improving imaging quality of chest CT and increasing diagnostic efficacy.

Objective:To investigate the clinical features, treatment and prognosis in pediatric Crohn′s disease (CD) with anal fistula.Methods:A retrospective case-control study was conducted. Clinical data of 66 children with CD diagnosed at the Department of Gastroenterology of Children′s Hospital of Nanjing Medical University from September 1st, 2014 to August 31th, 2020. According to the presence of anal fistula or not before diagnosis, the children were divided into anal fistula group and non-anal fistula group. The clinical features at initial onset between the above two groups were analyzed statistically. According to the use of infliximab (IFX) or not, children with anal fistula were divided into IFX group and non-IFX group and the clinical remission of anal fistula in the two groups was analyzed statistically.Results:Thirty CD children combined with anal fistula before diagnosis were set as anal fistula group, including 20 children of complex anal fistula and 10 of simple anal fistula. Eleven children underwent anal fistula incision-seton drainage and 19 did not receive surgery. The left 36 children without anal fistula were set as non-anal fistula group. The male proportion of children with anal fistula was higher than that of the children without anal fistula, and the difference was statistically significant (86.7% vs. 58.3%, P = 0.011) . Among the 30 children with anal fistula, 20 were treated with IFX-induced remission and maintenance therapy, and were set as IFX group, 10 were treated with enteral nutrition-induced remission and azathioprine-induced maintenance therapy, and were set as non-IFX group. The clinical remission rate of anal fistula in IFX group was significantly higher than that in non-IFX group after the follow-up period of 6 to 12 months (95% vs. 30%, P = 0.0001) . Conclusion:The CD children with anal fistula is more common in male, and the clinical remission rate of anal fistula is higher after IFX treatment.

Objective:To investigate the prevalence of rotavirus infection and susceptibility to Histo-Blood Group Antigens (HBGAs) in children with diarrhea under 5 years of age in Nanjing.Methods:Stool and corresponding saliva samples were collected from 295 children with acute diarrhea and 150 healthy children. Rotaviruses were detected in stool samples by antigen detection method, and rotavirus positive samples were genotyped by RT-PCR method. HBGA phenotype of saliva samples was determined by anti-tissue blood group monoclonal antibody ELISA method. Rotavirus infection and HBGA susceptibility were analyzed by statistical analysis.Results:In the case group, 139 (47.12%) of 295 samples were rotavirus positive, with G9[P8] genotype being the most common genotype (84.17%, 117/139). The proportion of fever ( χ2=34.81, P<0.001), vomiting ( χ2=25.01, P<0.001) and respiratory symptoms ( χ2=4.73, P=0.03) in rotavirus infected children, which were higher than those in non-rotavirus infected group, and the difference was statistically significant. In the ABO blood group system, type AB children were more likely to have diarrhea (95% CI: 1.029~2.622; P= 0.036), and type B children had a higher risk of rotavirus infection ( OR=1.783, 95% CI: 1.027~3.095, P= 0.039). In the secretory system antigens, secretory children were more prone to diarrhea and rotavirus infection, G9[P8] genotype infection was related to secretory phenotype ( OR=2.854, 95% CI: 1.641~4.962), and non-secretory children ( χ2=5.723, P=0.017) were less susceptible to rotavirus and G9[P8] genotype rotavirus infection. Conclusions:G9[P8] genotype was the main rotavirus infection in diarrhea children under 5 years of age in Nanjing, and individuals with secretory phenotype were more likely to be infected with G9[P8], which provided scientific basis for preventing and controlling rotavirus diarrhea in this area.

Objective:To investigate the clinical features, treatment and prognosis in pediatric Crohn′s disease (CD) with anal fistula.Methods:A retrospective case-control study was conducted. Clinical data of 66 children with CD diagnosed at the Department of Gastroenterology of Children′s Hospital of Nanjing Medical University from September 1st, 2014 to August 31th, 2020. According to the presence of anal fistula or not before diagnosis, the children were divided into anal fistula group and non-anal fistula group. The clinical features at initial onset between the above two groups were analyzed statistically. According to the use of infliximab (IFX) or not, children with anal fistula were divided into IFX group and non-IFX group and the clinical remission of anal fistula in the two groups was analyzed statistically.Results:Thirty CD children combined with anal fistula before diagnosis were set as anal fistula group, including 20 children of complex anal fistula and 10 of simple anal fistula. Eleven children underwent anal fistula incision-seton drainage and 19 did not receive surgery. The left 36 children without anal fistula were set as non-anal fistula group. The male proportion of children with anal fistula was higher than that of the children without anal fistula, and the difference was statistically significant (86.7% vs. 58.3%, P = 0.011) . Among the 30 children with anal fistula, 20 were treated with IFX-induced remission and maintenance therapy, and were set as IFX group, 10 were treated with enteral nutrition-induced remission and azathioprine-induced maintenance therapy, and were set as non-IFX group. The clinical remission rate of anal fistula in IFX group was significantly higher than that in non-IFX group after the follow-up period of 6 to 12 months (95% vs. 30%, P = 0.0001) . Conclusion:The CD children with anal fistula is more common in male, and the clinical remission rate of anal fistula is higher after IFX treatment.

Objective:To evaluate the correlation of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with the activity of pediatric Crohn′s disease (CD) , and to study the efficacy of NLR and PLR independently and combinedly in predicting active period of pediatric CD.Methods:A total of 43 children with CD (145 clinical records) admitted to Gastroenterology Department of Children′s Hospital of Nanjing Medical University from June 2017 to March 2020 were analyzed retrospectively. According to pediatric Crohn′s disease activity index, the clinical records were divided into inactive group (94 cases) , mild active group (29 cases) , moderate to severe active group (22 cases) . General information of the children and NLR and PLR results of each group on the second day after admission were collected.Results:The levels of NLR and PLR in mild active group and moderate to severe group were higher than those in inactive group [NLR: 2.96 (2.25, 4.12) vs. 1.10 (0.77, 1.92) , 3.25 (2.50, 5.53) vs. 1.10 (0.77, 1.92) ; PLR: 194.97 (143.30, 238.64) vs. 101.83 (81.75, 147.40) , 198.85 (166.95, 244.95) vs. 101.83 (81.75, 147.40) , P<0.001], but there was no significant difference between mild active group and moderate to severe active group. There were a strong positive correlation between NLR and PLR with CD activity ( rs = 0.622, P<0.001; rs = 0.582, P<0.001, respectively) . The cut-off values of NLR and PLR for predicting CD activity were 1.64 and 136.88, and the AUC was 0.877 and 0.855, respectively. The corresponding sensitivity and specificity were 96.08%, 71.28% and 84.31%, 74.47%, respectively. When NLR was combined with PLR, AUC was 0.891, sensitivity was 86.27%, and specificity was 78.72%. Conclusions:NLR and PLR can be used to distinguish the active and inactive periods of pediatric CD. The combination of NLR and PLR can be used to diagnose the active period of pediatric CD with higher AUC, sensitivity and specificity.

Objective:To evaluate the correlation of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with the activity of pediatric Crohn′s disease (CD) , and to study the efficacy of NLR and PLR independently and combinedly in predicting active period of pediatric CD.Methods:A total of 43 children with CD (145 clinical records) admitted to Gastroenterology Department of Children′s Hospital of Nanjing Medical University from June 2017 to March 2020 were analyzed retrospectively. According to pediatric Crohn′s disease activity index, the clinical records were divided into inactive group (94 cases) , mild active group (29 cases) , moderate to severe active group (22 cases) . General information of the children and NLR and PLR results of each group on the second day after admission were collected.Results:The levels of NLR and PLR in mild active group and moderate to severe group were higher than those in inactive group [NLR: 2.96 (2.25, 4.12) vs. 1.10 (0.77, 1.92) , 3.25 (2.50, 5.53) vs. 1.10 (0.77, 1.92) ; PLR: 194.97 (143.30, 238.64) vs. 101.83 (81.75, 147.40) , 198.85 (166.95, 244.95) vs. 101.83 (81.75, 147.40) , P<0.001], but there was no significant difference between mild active group and moderate to severe active group. There were a strong positive correlation between NLR and PLR with CD activity ( rs = 0.622, P<0.001; rs = 0.582, P<0.001, respectively) . The cut-off values of NLR and PLR for predicting CD activity were 1.64 and 136.88, and the AUC was 0.877 and 0.855, respectively. The corresponding sensitivity and specificity were 96.08%, 71.28% and 84.31%, 74.47%, respectively. When NLR was combined with PLR, AUC was 0.891, sensitivity was 86.27%, and specificity was 78.72%. Conclusions:NLR and PLR can be used to distinguish the active and inactive periods of pediatric CD. The combination of NLR and PLR can be used to diagnose the active period of pediatric CD with higher AUC, sensitivity and specificity.

Objective:To investigate the age of onset of functional constipation in children and to explore its relationship with possible factors.Methods:Four hundred and sixteen children with functional constipation who were admitted to the Digestive Specialist Clinic of Nanjing Children′s Hospital from January 2017 to December 2018 were divided into 4 groups (Q1-Q4) according to the quartiles of the onset age.The gender, duration of symptoms and constipation of their parents of the 4 groups were analyzed.Results:Age of onset of 416 children was (1.58±1.64) years, the age of onset in the Q1 group was (0.27±0.19) years, the age of onset in the Q2 group was (0.82±0.17) years, the age of onset in the Q3 group was (1.64±0.32) years, and the age of onset in the Q4 group was (3.91±1.83) years.The constipation duration in 416 patients was (1.50±1.62) years; the constipation duration of Q1, Q2 and Q4 groups was (2.20±1.95) years, (1.33±1.48) years, (1.11±1.05) years and (1.35±1.66) years, respectively, and the group with the youngest age of onset (Q1) had the longest duration of constipation, which was statistically significant compared with the other three groups ( F=9.644, P<0.05). Of the 416 children, 190 cases (45.7%) were boys, 226 cases (54.3%) were girls; 54 boys (50.9%) and 52 girls (49.1%) in the Q1 group, 47 boys (39.8%) and 71 girls (60.2%) in the Q2 group, 39 boys (40.6%) and 57 girls (59.4%) in the Q3 group; 53 boys (55.2%) and 43 girls (44.8%) in the Q4 group; there were no significant differences in gender ( χ2=7.210, P>0.05). Among 416 children with FC, 196 cases (47.1%) had at least one of their parents with constipation symptoms, including 61 cases (57.5%) in Q1 group, and 66 cases (55.9%) in Q2 group, 34 cases(35.4%) in Q3 group, 35 cases (36.5%) in Q4 group.The 2 groups (Q1-Q2) with younger onset compared with the older onset children (Q3-Q4), their parents were more likely to have constipation symptoms, and the difference was statistically significant ( χ2=17.96, P<0.05). Conclusions:The age of onset of functional constipation in children is young, and younger functional constipation children are less likely to receive formal guidance treatment at an early stage; gender has no significant relationship with the age of onset; children with a younger onset, genetic factors are more meaningful to them.