Objective:To investigate the impact of pre-treatment TPMT and NUDT15 genotyping on medication selection, tolerability and discontinuation rates of azathioprine or 6-mercaptopurine therapy in children with inflammatory bowel disease (IBD).Methods:A retrospective cohort study was conducted on 181 children with IBD who were scheduled for azathioprine or 6-mercaptopurine therapy at the Department of Gastroenterology, Children′s Hospital, Zhejiang University School of Medicine between January 2010 and January 2023. Among them, 168 children who received treatment were divided into a genotyped group and non-genotyped group based on pre-treatment TPMT and NUDT15 genotyping. The incidence of drug-related adverse reactions was compared between the two groups. The impact of genotyping on medication selection and discontinuation rates was analyzed. Chi-square test or Fisher exact test were used for intergroup comparisons. Logistic regression analysis was used to control the confounding factors. Firth Logistic regression analysis was applied for data with complete separation. The probability of discontinuation was assessed using survival analysis with Cox proportional hazards modeling.Results:Among the 181 children with IBD, 13 did not receive azathioprine or 6-mercaptopurine due to genetic variants, while the remaining 168 underwent the therapy (154 cases of Crohn′s disease and 14 cases ulcerative colitis; 108 males and 60 females). Excluding the 13 untreated cases, 77 children underwent TPMT and NUDT15 genotyping were assigned to the genotyped group, and the remaining 91 to the non-genotyped group. Adverse reactions included myelosupression (26 cases,15.5%), hepatotoxicity (18 cases,10.7%), gastrointestinal disturbance (25 cases,14.9%), alopecia (12 cases,7.1%), fever (3 cases,1.8%), rash (2 cases,1.2%), and pancreatitis (1 case,0.6%). The incidence of overall adverse reactions was significantly higher in the non-genotyped group compared to that of the genotyped group (40.7% (37/91) vs. 26.0% (20/77), P<0.05). Specifically, the non-genotyped group had a higher rate of gastrointestinal reactions compared to the genotyped group (24.2% (22/91) vs. 3.3% (3/77), P<0.01). Cox regression analysis revealed that non-genotyped group had a higher risk of treatment discontinuation due to the adverse reactions ( HR=1.47, 95% CI 0.65-3.30). Conclusion:Pre-treatment genotyping of TPMT and NUDT15 variants can help guide the selection of clinical drugs, reduce the incidence of drug-related adverse reactions and enhance tolerability of azathioprine or 6-mercaptopurine therapy in IBD children.

Objective:To investigate the impact of pre-treatment TPMT and NUDT15 genotyping on medication selection, tolerability and discontinuation rates of azathioprine or 6-mercaptopurine therapy in children with inflammatory bowel disease (IBD).Methods:A retrospective cohort study was conducted on 181 children with IBD who were scheduled for azathioprine or 6-mercaptopurine therapy at the Department of Gastroenterology, Children′s Hospital, Zhejiang University School of Medicine between January 2010 and January 2023. Among them, 168 children who received treatment were divided into a genotyped group and non-genotyped group based on pre-treatment TPMT and NUDT15 genotyping. The incidence of drug-related adverse reactions was compared between the two groups. The impact of genotyping on medication selection and discontinuation rates was analyzed. Chi-square test or Fisher exact test were used for intergroup comparisons. Logistic regression analysis was used to control the confounding factors. Firth Logistic regression analysis was applied for data with complete separation. The probability of discontinuation was assessed using survival analysis with Cox proportional hazards modeling.Results:Among the 181 children with IBD, 13 did not receive azathioprine or 6-mercaptopurine due to genetic variants, while the remaining 168 underwent the therapy (154 cases of Crohn′s disease and 14 cases ulcerative colitis; 108 males and 60 females). Excluding the 13 untreated cases, 77 children underwent TPMT and NUDT15 genotyping were assigned to the genotyped group, and the remaining 91 to the non-genotyped group. Adverse reactions included myelosupression (26 cases,15.5%), hepatotoxicity (18 cases,10.7%), gastrointestinal disturbance (25 cases,14.9%), alopecia (12 cases,7.1%), fever (3 cases,1.8%), rash (2 cases,1.2%), and pancreatitis (1 case,0.6%). The incidence of overall adverse reactions was significantly higher in the non-genotyped group compared to that of the genotyped group (40.7% (37/91) vs. 26.0% (20/77), P<0.05). Specifically, the non-genotyped group had a higher rate of gastrointestinal reactions compared to the genotyped group (24.2% (22/91) vs. 3.3% (3/77), P<0.01). Cox regression analysis revealed that non-genotyped group had a higher risk of treatment discontinuation due to the adverse reactions ( HR=1.47, 95% CI 0.65-3.30). Conclusion:Pre-treatment genotyping of TPMT and NUDT15 variants can help guide the selection of clinical drugs, reduce the incidence of drug-related adverse reactions and enhance tolerability of azathioprine or 6-mercaptopurine therapy in IBD children.

Iron is an essential element for living organisms that plays critical roles in the process of bacterial growth and metabolism. However, it remains to be elucidated whether piuB encoding iron-uptake factor is involved in iron uptake and pathogenicity of Xanthomonas axonopodis pv. glycines (Xag). To investigate the function of piuB, we firstly generated a piuB deletion mutant (ΔpiuB) by homologous recombination. Compared with the wild-type, the piuB mutant exhibited significantly reduced growth and virulence in host soybean. The mutant displayed markedly increased siderophore secretory volume, and its sensitivity to Fe³⁺, Cu²⁺, Zn²⁺ and Mn²⁺ was significantly enhanced. Additionally, the H₂O₂ resistance, exopolysaccharide yield, biofilm formation, and cell mobility of ΔpiuB were significantly diminished compared to that of the wild-type. The addition of exogenous Fe³⁺ cannot effectively restore the above characteristics of ΔpiuB. However, expressing piuB in trans rescued the properties lost by ΔpiuB to the levels in the wild-type. Taken together, our results demonstrated that PiuB is a potential factor for Xag to assimilate Fe³⁺, and is necessary for Xag to be pathogenic in host soybean.
Iron ; Glycine max ; Virulence ; Xanthomonas axonopodis/genetics* ; Hydrogen Peroxide

Diacylglycerol o-acyltransferase 1（DGAT1）is the key enzyme in fat metabolism.When DGAT1 gene who encodes this enzyme is mutated，it can affect the intracellular fat metabolism in organism with various clinical manifestations.DGAT1 gene deficiency is one of the causes of congenital diarrhea and enteropathies.The onset age in patients with DGAT1 deficiency is early.The main clinical manifestations of such patients include protein-losing enteropathy，malnutrition and other nutritional disorders.There is no specific drug for such disease so far.Early identification of DGAT1 deficiency and nutritional therapy in early infancy can treat this disease effectively and improve the prognosis.

Objective: To analyze the clinical characteristics of X-linked inhibitor of apoptosis (XIAP) deficient patients with clinical manifestation of Crohn's disease. Methods: Clinical manifestations, laboratory investigations, genetic testing and therapeutic interventions of one case of XIAP deficiency who was admitted to Department of Gastroenterology in Children's Hospital, Zhejiang University School of Medicine in May 2016 were summarized. PubMed and Chinese database for articles published from January 2016 to June 2017 were searched using the key words of'Crohn's disease’and'XIAP’, and the relevant literature was reviewed. Results: The case we reported was a 6-year-1-month-old boy with recurrent bloody stool for 2 months, and abdominal pain with fever for 2 weeks. The patient had a past history of hemophagocytic lymphohistiocytosis (HLH) and epilepsy in the past one year. Complete blood cell count showed mild anemia (Hb108 g/L). The patient had an elevated high-sensitivity C reactive protein (86 mg/L) and erythrocyte sedimentation rate (46 mm/1h) . White blood cells, pus cells and red blood cells were found on routine stool examination. Biochemical panel showed hypoalbuminemia (25.2 g/L) , elevated transaminase (alanine aminotransferase 175 U/L, aspartate transaminase 229 U/L) , hypertriglyceridemia (4.41 mmol/L) , and hyperferritinemia (>1 650.0 μg/L) . Magnetic resonance enterography revealed the intestinal wall thickening and increased enhancement in parts of illeum and colon. Capsule endoscopy revealed multiple ulcers in jejunum. Colonoscopy showed multiple ulcers in colon and the pathological examination revealed chronic inflammation in mucosa of terminal ileum and colon, which was combined with partial necrosis and ulceration. Some phagocytes were seen in bone marrow smears. The patient was given multiple diagnoses, including hemophagocytic lymphohistiocytosis, Crohn's disease, sepsis, epilepsy, severe malnutrition, and hypoproteinemia. The pediatric Crohn's disease activity index (PCDAI) was 37.5. Genetic testing identified a hemizygotic mutation of c.910G>T chrX:123022501 p.G304X in XIAP. The parents had no such mutation. The patient showed response to infliximab with oral intake of mercaptopurine and corticosteroids, and had remission with PCDAI of 0. There were 9 relevant articles (Chinese 0 English 9), which showed 33.3% XIAP deficient patients manifested with inflammatory bowel disease(IBD), who might have other manifestations such as hemophagocytic lymphohistiocytosis or splenomegaly simultaneously or sequentially. Those patients showed poor response to monotherapy. Conclusion XIAP deficient patients have various clinical manifestations. Genetic testing is important to those male pediatric IBD patients who have the complicated symptoms or little response to standard therapy.