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 analyze the clinical and genetic features of four children with pediatric acute liver failure (PALF) caused by neuroblastoma-amplified sequence ( NBAS) gene variant, as well as the correlation between clinical phenotype and genotype. Methods:The clinical data and genetic test results of four children with NBAS gene variants admitted to the Department of Gastroenterology, Children's Hospital Affiliated to Zhejiang University School of Medicine from August 2015 to June 2023 mainly presenting with pediatric acute liver failure (PALF) were retrospectively analyzed. The relevant literature from January 2015 to May 2024 was retrieved using the Chinese and English keywords " NBAS," "neuroblastoma amplified sequence," "SOPH," "short stature with optic nerve atrophy and Pelger Hu?t anomaly," "liver failure," and "neuroblastoma amplified sequence" indexed in the CNKI database, Wanfang Data Knowledge Service Platform, and PubMed database. The clinical features and gene mutation characteristics of domestic patients were summarized. Results:The age at which the initial PALF attack occurred in the four children varied from eight months to three years and seven months. All patients developed PALF within 1-2 days after the onset of fever, with symptoms such as vomiting, convulsions, and mental depression or confusion, accompanied by a sharp increase in transaminases, elevated bilirubin and blood ammonia, hyperlactatemia, and hepatomegaly. The PALF gradually improved, and three pediatric patients showed extrahepatic manifestations following antipyretic, fluid replacement, and other symptomatic supportive treatment. Long-term follow-up showed that active temperature control and symptomatic therapy reduced the recurrence of PALF. Genetic testing identified eight kinds of NBAS gene variants sites. Family testing validated compound heterozygous variants, which included four missense variants, one nonsense variants, and three frameshift mutations. A literature study revealed that out of 51 Chinese patients with NBAS gene variants, 98.0% (50/51) had liver involvement, and 37 cases showed PALF. A total of 61 mutation sites were identified, with c.3596G>A (45.1%, 23/51) as a hotspot variants. Conclusions:PALF caused by NBAS gene variant has obvious clinical and genetic characteristics, and there is a correlation between genotype and clinical phenotype. The c.3596G>A variant site is a hotspot mutation in China and is strongly correlated with the liver failure phenotype.

OBJECTIVE To investigate the construction and practice of a drug traceability code management system in pediatric hospitals， providing a reference for promoting drug traceability code collection in healthcare institutions. METHODS Taking the outpatient pharmacy of our hospital as the research subject， a drug traceability code management system was constructed through the upgrade of the hospital information system （HIS）， process optimization， and human-machine collaboration mechanism. The PDCA （plan-do-check-act） cycle management method was applied to continuously optimize this system. Based on operational data from March 2024 to February 2025， the changes in the collection rate of drug traceability codes were analyzed， and the differences in the average patient pickup time， the average pharmacist dispensing time， and the dispensing error rate were compared before and after the implementation of the system. RESULTS In the initial period of trial operation of the drug traceability code management system（June 2024）， the collection rate of drug traceability codes was 57.17%， which subsequently improved to 93.52% by February 2025 following process optimization. Compared with the pre-implementation period （March-May 2024）， there was no significant difference （P＞0.05） in the average patient pickup time during the stable run-in period （August-October 2024）； the overall average pharmacist dispensing time increased significantly （P＜0.001）， but the clinical significance of this increase （0.42 s） was limited； stratified analyses showed a significant increase in the average pharmacist dispensing time for prescriptions involving chronic disease multidrug combinations （[ 23.29±6.83） s vs. （17.87±3.64 ） s， P＜0.001]； the dispensing error rate was reduced from 0.13‰ to 0.03‰ （P＝0.038）. CONCLUSIONS By adopting the strategy of “system reconstruction-process reengineering-human-machine collaboration”， our hospital has successfully established a drug traceability code management system. While complying with national regulatory requirements， we have maintained service efficiency and reduced the medication dispensing error rate.

Objective:To investigatethe effects of different blood lead levels on indicators of immune function in occupationally lead-exposed populations.Methods:From October to December 2023, a total of 126 occupationally exposed lead workers of a company in Guizhou Province were selected, and their basic information was collected through questionnaires. Inductively coupled plasma mass spectrometry was used to detect blood lead levels in the study population. Workers were categorized into Group 1, Group 2 and Group 3 based on blood lead levels (blood lead levels <200 μg/L, 200~400 μg/L and >400 μg/L). Lymphocyte subpopulation marker leukocyte differentiation antigen (CD) in peripheral blood and interleukin (IL) -1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, tumor necrosis factor-alpha (TNF-α), and interferon (IFN) -γ in serum were examined by flow cytometry. Serum levels of immunoglobulin (Ig) A, IgG, IgM, and complement proteins (C3, C4) were measured by immunoscattering turbidimetry. Data were statistically analyzed using rank sum test, Chi-square test or Fisher exact probability method for multiple samples.Results:Compared with group 1, the percentage of CD3 +CD8 + and CD4 +CD25 + cells decreased ( P<0.05) and the percentage of CD4 + CD95 + cells increased in the lead-exposed populations in groups 2 and 3 ( P<0.05) ; however, the serum IL-1β, IL-2, IL- 5, IL-8, IL-12p70, and IFN-γ levels were decreased ( P<0.05) in group 3. Meanwhile, IgG ( P<0.05) and IgM levels in serum of lead-exposed population in group 2 and group 3 were reduced ( P<0.05) comparing with group 1. Spearman correlation analysis showed that blood lead levels of workers were negatively correlated with the percentage of peripheral blood CD8 +CD95 + cells, CD3 +CD8 + cells, CD3 -CD16 + CD56 + cells, IgG, IgM, and IgA ( rs=-0.20, -0.22, -0.23, -0.24, -0.26, -0.35, P<0.05), but was positively correlated with the level of CD3 +CD4 + cells ( rs= 0.18, P<0.05). Regression analysis revealed that blood lead level was a risk factor for the percentage of CD8 +CD95 + cells, CD3 +CD8 + cells, CD3 -CD16 + CD56 + cells, IgG, IgM, and IgA ( P<0.05) . Conclusion:Different lead loads can lead to abnormal changes in peripheral blood lymphocyte subsets, cytokines, and immunoglobulin levels in occupationally lead-exposed people. Lead exposure in occupationally lead-exposed populations may affect their immune function.

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 analyze the clinical and genetic features of four children with pediatric acute liver failure (PALF) caused by neuroblastoma-amplified sequence ( NBAS) gene variant, as well as the correlation between clinical phenotype and genotype. Methods:The clinical data and genetic test results of four children with NBAS gene variants admitted to the Department of Gastroenterology, Children's Hospital Affiliated to Zhejiang University School of Medicine from August 2015 to June 2023 mainly presenting with pediatric acute liver failure (PALF) were retrospectively analyzed. The relevant literature from January 2015 to May 2024 was retrieved using the Chinese and English keywords " NBAS," "neuroblastoma amplified sequence," "SOPH," "short stature with optic nerve atrophy and Pelger Hu?t anomaly," "liver failure," and "neuroblastoma amplified sequence" indexed in the CNKI database, Wanfang Data Knowledge Service Platform, and PubMed database. The clinical features and gene mutation characteristics of domestic patients were summarized. Results:The age at which the initial PALF attack occurred in the four children varied from eight months to three years and seven months. All patients developed PALF within 1-2 days after the onset of fever, with symptoms such as vomiting, convulsions, and mental depression or confusion, accompanied by a sharp increase in transaminases, elevated bilirubin and blood ammonia, hyperlactatemia, and hepatomegaly. The PALF gradually improved, and three pediatric patients showed extrahepatic manifestations following antipyretic, fluid replacement, and other symptomatic supportive treatment. Long-term follow-up showed that active temperature control and symptomatic therapy reduced the recurrence of PALF. Genetic testing identified eight kinds of NBAS gene variants sites. Family testing validated compound heterozygous variants, which included four missense variants, one nonsense variants, and three frameshift mutations. A literature study revealed that out of 51 Chinese patients with NBAS gene variants, 98.0% (50/51) had liver involvement, and 37 cases showed PALF. A total of 61 mutation sites were identified, with c.3596G>A (45.1%, 23/51) as a hotspot variants. Conclusions:PALF caused by NBAS gene variant has obvious clinical and genetic characteristics, and there is a correlation between genotype and clinical phenotype. The c.3596G>A variant site is a hotspot mutation in China and is strongly correlated with the liver failure phenotype.

Objective:To investigatethe effects of different blood lead levels on indicators of immune function in occupationally lead-exposed populations.Methods:From October to December 2023, a total of 126 occupationally exposed lead workers of a company in Guizhou Province were selected, and their basic information was collected through questionnaires. Inductively coupled plasma mass spectrometry was used to detect blood lead levels in the study population. Workers were categorized into Group 1, Group 2 and Group 3 based on blood lead levels (blood lead levels <200 μg/L, 200~400 μg/L and >400 μg/L). Lymphocyte subpopulation marker leukocyte differentiation antigen (CD) in peripheral blood and interleukin (IL) -1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17, tumor necrosis factor-alpha (TNF-α), and interferon (IFN) -γ in serum were examined by flow cytometry. Serum levels of immunoglobulin (Ig) A, IgG, IgM, and complement proteins (C3, C4) were measured by immunoscattering turbidimetry. Data were statistically analyzed using rank sum test, Chi-square test or Fisher exact probability method for multiple samples.Results:Compared with group 1, the percentage of CD3 +CD8 + and CD4 +CD25 + cells decreased ( P<0.05) and the percentage of CD4 + CD95 + cells increased in the lead-exposed populations in groups 2 and 3 ( P<0.05) ; however, the serum IL-1β, IL-2, IL- 5, IL-8, IL-12p70, and IFN-γ levels were decreased ( P<0.05) in group 3. Meanwhile, IgG ( P<0.05) and IgM levels in serum of lead-exposed population in group 2 and group 3 were reduced ( P<0.05) comparing with group 1. Spearman correlation analysis showed that blood lead levels of workers were negatively correlated with the percentage of peripheral blood CD8 +CD95 + cells, CD3 +CD8 + cells, CD3 -CD16 + CD56 + cells, IgG, IgM, and IgA ( rs=-0.20, -0.22, -0.23, -0.24, -0.26, -0.35, P<0.05), but was positively correlated with the level of CD3 +CD4 + cells ( rs= 0.18, P<0.05). Regression analysis revealed that blood lead level was a risk factor for the percentage of CD8 +CD95 + cells, CD3 +CD8 + cells, CD3 -CD16 + CD56 + cells, IgG, IgM, and IgA ( P<0.05) . Conclusion:Different lead loads can lead to abnormal changes in peripheral blood lymphocyte subsets, cytokines, and immunoglobulin levels in occupationally lead-exposed people. Lead exposure in occupationally lead-exposed populations may affect their immune function.

Objective:To analyze the efficacy of switching to adalimumab (ADA) treatment in pediatric with inflammatory bowel disease (IBD) after failure of infliximab (IFX) treatment.Methods:Clinical data of children with IBD who were treated at the Children's Hospital of Zhejiang University School of Medicine from January 2019 to May 2023 and switched to ADA treatment after IFX treatment failure were retrospectively included. The clinical symptoms, laboratory results, disease activity index of pediatrics, and endoscopic severity scores under colonoscopy were compared between baseline, treatment after 3 months and 12 months.Results:A total of 47 IBD patients were enrolled, including 36 cases of Crohn's disease, 4 cases of ulcerative colitis, and 7 cases of IBD unclassified. There were 28 male and 19 female patients. Among patients who were converted to ADA treatment, 31/47 (66.0%) had low trough concentration and high anti-IFX antibodies, 12/47 (25.5%) had allergic reactions to IFX, and 4/47 (8.5%) had low IFX trough concentration and no anti-IFX antibody. The overall 12 month retention rate of IBD patients who converted to ADA treatment after IFX treatment was 76.6% (36/47). After 3 months of ADA treatment, compared to the baseline, in body mass index for age, height for age, and serum albumin levels increased, while inflammatory markers such as high sensitivity C reactive protein, erythrocyte sedimentation rate, and pediatric Crohn's disease activity index scores decreased. Compared to 3 months of treatment, nutritional and inflammatory markers after 12 months of treatment were stable. No serious adverse reactions or severe infections were found. Six (13%) patients who had pain and swelling at the injection site. Two patients were detected to have high titers of antibodies.Conclusions:Pediatric IBD patients switched to ADA treatment after failure of IFX treatment with ADA for 3 months improves nutrition status and serum albumin levels, while reducing inflammatory markers and disease activity. No serious adverse reactions are found. Application of ADA after failure of IFX treatment provides a practical basis for converting biological agents for pediatric IBD.

Objective:To analyze the efficacy of switching to adalimumab (ADA) treatment in pediatric with inflammatory bowel disease (IBD) after failure of infliximab (IFX) treatment.Methods:Clinical data of children with IBD who were treated at the Children's Hospital of Zhejiang University School of Medicine from January 2019 to May 2023 and switched to ADA treatment after IFX treatment failure were retrospectively included. The clinical symptoms, laboratory results, disease activity index of pediatrics, and endoscopic severity scores under colonoscopy were compared between baseline, treatment after 3 months and 12 months.Results:A total of 47 IBD patients were enrolled, including 36 cases of Crohn's disease, 4 cases of ulcerative colitis, and 7 cases of IBD unclassified. There were 28 male and 19 female patients. Among patients who were converted to ADA treatment, 31/47 (66.0%) had low trough concentration and high anti-IFX antibodies, 12/47 (25.5%) had allergic reactions to IFX, and 4/47 (8.5%) had low IFX trough concentration and no anti-IFX antibody. The overall 12 month retention rate of IBD patients who converted to ADA treatment after IFX treatment was 76.6% (36/47). After 3 months of ADA treatment, compared to the baseline, in body mass index for age, height for age, and serum albumin levels increased, while inflammatory markers such as high sensitivity C reactive protein, erythrocyte sedimentation rate, and pediatric Crohn's disease activity index scores decreased. Compared to 3 months of treatment, nutritional and inflammatory markers after 12 months of treatment were stable. No serious adverse reactions or severe infections were found. Six (13%) patients who had pain and swelling at the injection site. Two patients were detected to have high titers of antibodies.Conclusions:Pediatric IBD patients switched to ADA treatment after failure of IFX treatment with ADA for 3 months improves nutrition status and serum albumin levels, while reducing inflammatory markers and disease activity. No serious adverse reactions are found. Application of ADA after failure of IFX treatment provides a practical basis for converting biological agents for pediatric IBD.

Objective:To investigate the interaction of platelet factor 4(PF4)with tumor necrosis factor-α(TNF-α)in the pathoge-nesis of chronic periodontitis(Ⅲ-C).Methods:22 patients with chronic periodontitis(Ⅲ-C)and 22 subjects with periodontal health were recruited.Before and after periodontal treatment,the concentration of PF4 and TNF-α in gingival crevicular fluid(GCF)and ser-um,the amount of PF4 released by platelets after lipopolysaccharide(LPS)stimulated peripheral blood platelets were measured by ELISA.Flow cytometry was used to calculate the number of platelets in GCF before and after treatment.Results:The concentrations of PF4 and TNF-α in the GCF and serum of the patients were higher than those in the periodontal healthy group(P＜0.05).After treat-ment,the concentrations of PF4 and TNF-α in the GCF were significantly lower than those before treatment(P＜0.05),and the con-centrations of PF4 and TNF-α in the serum were unchanged(P＞0.05).After LPS stimulation of the platelets in blood before and after treatment,the concentration of PF4 released by the platelets was much higher in the patients than that in the healthy controls(P＜0.01),and the concentration was significantly lower after periodontal treatment than before treatment(P＜0.01).The number of CD41/CD61 double positive platelets and CD45 negative cells in GCF before periodontal treatment were 85 times and 87 times higher than those in periodontal healthy subjects,respectively(P＜0.01).Conclusion:PF4 and TNF-α have synergistic effect in the patho-genesis of chronic periodontitis.