Objective To explore the risk factors analysis and prediction model establishment of restenosis dysfunction at 1 year after percutaneous transluminal angioplasty(PTA)of internal arteriovenous fistula based on machine learning.Methods A total of 322 patients who underwent PTA of internal arteriovenous fistula in Wenzhou Central Hospital from June 1,2018 to December 31,2023 were enrolled.The operation-related data were collected.Variables were used to construct prediction models using five machine learning algorithms:Random forest(RF),extreme gradient boosting(XGBoost),support vector machine(SVM),gradient boosting decision tree(GBDT)and Logistic regression(LR).The predictive efficacy was evaluated by area under receiver operating characteristic curve.Results There were 97 cases of restenosis dysfunction and 225 cases of non-dysfunction.The incidence of internal fistula restenosis dysfuction was 30.1％1 year after PTA.The age,diabetes,smoking,calcium-phosphorus product,dilatation pressure ≥20mmHg,and balloon diameter ≥6mnm in dysfunction group were higher than those in non-dysfunction group.The difference was statistically significant(P＜0.05).The area under the curve of RF,XGBoost,SVM,GBDT and LR models based on machine learning was 0.908(95％CI:0.836-0.980),0.809(95％CI:0.696-0.922),0.745(95％CI:0.624-0.867),0.711(95％CI:0.576-0.847)and 0.651(95％CI:0.508-0.795),respectively.The sensitivity was 79.1％,70.8％,83.3％,62.5％and 72.3％,respectively.The specificity was 89.0％,81.2％,57.8％,78.9％and 71.0％,respectively.Conclusion Age,diabetes mellitus,smoking,calcium-phosphorus product,expansion pressure ≥20mnmHg,balloon diameter ≥ 6mm are independent risk factors for restenosis failure after PTA in patients with internal arteriovenous fistula,which can be used as an index to predict restenosis failure 1 year after PTA in internal arteriovenous fistula.The random forest prediction model based on machine learning algorithm has good prediction performance and can better predict restenosis failure 1 year after PTA in internal arteriovenous fistula.

Objective:To understand the molecular evolutionary characteristics of the recombinant strain GII.3[P12] of norovirus acute gastroenteritis outbreaks and aggregated outbreaks in China from 2022 to 2023.Methods:Epidemiological information, case information, clinical samples, as well as detection and genotyping information of norovirus outbreaks and aggregated outbreaks from 2022 to 2023 were collected; positive samples of the GII.3[P12] recombinant strain were subjected to nucleic acid extraction, whole-genome amplification, and sequence analysis; and homology simulation method were used to construct a three-dimensional structure and predict antigenic epitopes.Results:From January 2022 to December 2023, a total of 1 136 norovirus outbreaks and aggregated outbreaks were reported in China′s norovirus outbreak surveillance network, and genotyping result were successfully obtained for 942 outbreaks, with GII dominating, accounting for 76.0% (716/942), and the proportion of GI and mixed genotypes being 15.8% (149/942) and 8.2% (77/942). Norovirus outbreaks caused by GII were dominated by GII.3[P12] (22.5%, 161/716), while other major genotypes included GII.17[P17] (18.7%, 134/716), GII.4_Sydney 2012[P16] (11.6%, 83/716) and GII.6[P7] ( 11.3%, 81/716). 2022-2023 Outbreaks caused by GII.3[P12] were concentrated in February-March (54.0%, 87/161), with the main outbreaks occurring in nursery and primary schools (87.5%), the mode of transmission was mainly human-to-human (68.9%), and the main susceptible population was children aged 3-7 years (93.3%). In this study, the genome sequences of 25 GII.3[P12] recombinant strains were obtained, and according to the phylogenetic analysis, it was shown that the GII.3[P12] recombinant strains in China in 2022-2023 belonged to the Cluster IV cluster of sublineage b (7 strains) and sublineage c (18 strains). A total of 11 linear and 8 conformational epitopes were predicted by epitope prediction analysis, and the predicted linear and conformational epitopes had overlapping positions, and each conformational epitope was part of the predicted linear epitope with conserved potential antigen-binding and receptor-binding sites.Conclusions:The recombinant strain GII.3[P12] is one of the epidemic strains that will cause outbreaks and clusters of norovirus in China in 2022-2023, and its genome did not undergo significant mutation.

Objective To explore the risk factors analysis and prediction model establishment of restenosis dysfunction at 1 year after percutaneous transluminal angioplasty(PTA)of internal arteriovenous fistula based on machine learning.Methods A total of 322 patients who underwent PTA of internal arteriovenous fistula in Wenzhou Central Hospital from June 1,2018 to December 31,2023 were enrolled.The operation-related data were collected.Variables were used to construct prediction models using five machine learning algorithms:Random forest(RF),extreme gradient boosting(XGBoost),support vector machine(SVM),gradient boosting decision tree(GBDT)and Logistic regression(LR).The predictive efficacy was evaluated by area under receiver operating characteristic curve.Results There were 97 cases of restenosis dysfunction and 225 cases of non-dysfunction.The incidence of internal fistula restenosis dysfuction was 30.1％1 year after PTA.The age,diabetes,smoking,calcium-phosphorus product,dilatation pressure ≥20mmHg,and balloon diameter ≥6mnm in dysfunction group were higher than those in non-dysfunction group.The difference was statistically significant(P＜0.05).The area under the curve of RF,XGBoost,SVM,GBDT and LR models based on machine learning was 0.908(95％CI:0.836-0.980),0.809(95％CI:0.696-0.922),0.745(95％CI:0.624-0.867),0.711(95％CI:0.576-0.847)and 0.651(95％CI:0.508-0.795),respectively.The sensitivity was 79.1％,70.8％,83.3％,62.5％and 72.3％,respectively.The specificity was 89.0％,81.2％,57.8％,78.9％and 71.0％,respectively.Conclusion Age,diabetes mellitus,smoking,calcium-phosphorus product,expansion pressure ≥20mnmHg,balloon diameter ≥ 6mm are independent risk factors for restenosis failure after PTA in patients with internal arteriovenous fistula,which can be used as an index to predict restenosis failure 1 year after PTA in internal arteriovenous fistula.The random forest prediction model based on machine learning algorithm has good prediction performance and can better predict restenosis failure 1 year after PTA in internal arteriovenous fistula.

Objective:To understand the molecular evolutionary characteristics of the recombinant strain GII.3[P12] of norovirus acute gastroenteritis outbreaks and aggregated outbreaks in China from 2022 to 2023.Methods:Epidemiological information, case information, clinical samples, as well as detection and genotyping information of norovirus outbreaks and aggregated outbreaks from 2022 to 2023 were collected; positive samples of the GII.3[P12] recombinant strain were subjected to nucleic acid extraction, whole-genome amplification, and sequence analysis; and homology simulation method were used to construct a three-dimensional structure and predict antigenic epitopes.Results:From January 2022 to December 2023, a total of 1 136 norovirus outbreaks and aggregated outbreaks were reported in China′s norovirus outbreak surveillance network, and genotyping result were successfully obtained for 942 outbreaks, with GII dominating, accounting for 76.0% (716/942), and the proportion of GI and mixed genotypes being 15.8% (149/942) and 8.2% (77/942). Norovirus outbreaks caused by GII were dominated by GII.3[P12] (22.5%, 161/716), while other major genotypes included GII.17[P17] (18.7%, 134/716), GII.4_Sydney 2012[P16] (11.6%, 83/716) and GII.6[P7] ( 11.3%, 81/716). 2022-2023 Outbreaks caused by GII.3[P12] were concentrated in February-March (54.0%, 87/161), with the main outbreaks occurring in nursery and primary schools (87.5%), the mode of transmission was mainly human-to-human (68.9%), and the main susceptible population was children aged 3-7 years (93.3%). In this study, the genome sequences of 25 GII.3[P12] recombinant strains were obtained, and according to the phylogenetic analysis, it was shown that the GII.3[P12] recombinant strains in China in 2022-2023 belonged to the Cluster IV cluster of sublineage b (7 strains) and sublineage c (18 strains). A total of 11 linear and 8 conformational epitopes were predicted by epitope prediction analysis, and the predicted linear and conformational epitopes had overlapping positions, and each conformational epitope was part of the predicted linear epitope with conserved potential antigen-binding and receptor-binding sites.Conclusions:The recombinant strain GII.3[P12] is one of the epidemic strains that will cause outbreaks and clusters of norovirus in China in 2022-2023, and its genome did not undergo significant mutation.

Objective:To analyze the effect of Iron deficiency anemia (IDA) and Black stain (BS) on the microbial community of dental plaque.Methods:A total of 136 preschool children aged 3 to 6 years old from 12 kindergartens in Shinan District and Shibei District of Qingdao City were investigated by using a cluster sampling method from April to May 2019. They were divided into two groups based on oral examination: the early childhood caries (ECC) group and the caries-free (CF) group. According to whether they had IDA and BS, they were further divided into four groups: the IDA with caries (IDA-ECC) group, the non-IDA with caries (NIDA-ECC) group, the BS without caries (BS-CF) group and the non-BS without caries (NBS-CF) group. The gingival plaque of the study subjects was collected. The 16S rRNA gene was sequenced by using Illumina MiSeq high-throughput sequencing technology. The composition, community structure and different bacteria genera of the microbial communities between the groups were compared and analyzed. Potential biomarkers within each group were further identified by linear discriminant analysis of effect size (LEfSe).Results:The 136 children were aged (5.11±0.87) years old, with 80 boys (58.82%). There were statistically significant differences in the microbial composition, structure and function of oral plaque between the ECC and CF groups ( P<0.05). There were statistically significant differences in the microbial richness and diversity of oral plaque between the IDA-ECC and NIDA-ECC groups ( P<0.05). There was no significant difference in microbial diversity index between the BS-CF and NBS-CF groups ( P>0.05). The LEfSe analysis results showed that 41, 31 and 9 taxa with different relative abundance were identified between the ECC and CF groups, IDA-ECC and NIDA-ECC groups, and BS-CF and NBS-CF groups, respectively. Conclusion:IDA and BS have an effect on the microecological diversity and microbial community function of oral plaque in young children with early childhood caries.

Objective:To analyze the effect of Iron deficiency anemia (IDA) and Black stain (BS) on the microbial community of dental plaque.Methods:A total of 136 preschool children aged 3 to 6 years old from 12 kindergartens in Shinan District and Shibei District of Qingdao City were investigated by using a cluster sampling method from April to May 2019. They were divided into two groups based on oral examination: the early childhood caries (ECC) group and the caries-free (CF) group. According to whether they had IDA and BS, they were further divided into four groups: the IDA with caries (IDA-ECC) group, the non-IDA with caries (NIDA-ECC) group, the BS without caries (BS-CF) group and the non-BS without caries (NBS-CF) group. The gingival plaque of the study subjects was collected. The 16S rRNA gene was sequenced by using Illumina MiSeq high-throughput sequencing technology. The composition, community structure and different bacteria genera of the microbial communities between the groups were compared and analyzed. Potential biomarkers within each group were further identified by linear discriminant analysis of effect size (LEfSe).Results:The 136 children were aged (5.11±0.87) years old, with 80 boys (58.82%). There were statistically significant differences in the microbial composition, structure and function of oral plaque between the ECC and CF groups ( P<0.05). There were statistically significant differences in the microbial richness and diversity of oral plaque between the IDA-ECC and NIDA-ECC groups ( P<0.05). There was no significant difference in microbial diversity index between the BS-CF and NBS-CF groups ( P>0.05). The LEfSe analysis results showed that 41, 31 and 9 taxa with different relative abundance were identified between the ECC and CF groups, IDA-ECC and NIDA-ECC groups, and BS-CF and NBS-CF groups, respectively. Conclusion:IDA and BS have an effect on the microecological diversity and microbial community function of oral plaque in young children with early childhood caries.

Objective:To explore the therapeutic efficacy and toxicity of oral Etoposide chemotherapy in children with disseminated medulloblastoma (MB) after the standard treatment plan.Methods:The clinical data of 86 children with disseminated MB admitted in the Department of Pediatrics, Beijing Shijitan Hospital of Capital Medical University from January 2016 to May 2020 were analyzed retrospectively.The median age of children was 8.8 (3.0-16.7) years old.Among them, 33 children treated with maintenance chemotherapy via oral Etoposide were included in the chemotherapy group, and 53 children without oral maintenance chemotherapy were included in the non-chemotherapy group.The gender distribution, surgical resection range, pathological type, molecular classification, postoperative mutism, M-stage and survival[progression-free survival (PFS) and overall survival (OS)] of the 2 groups were compared.The main adverse events of oral Etoposide chemotherapy were recorded. Chi- square test is used for data comparison, Kaplan-Meier method was used to plot the survival curve of disseminated MB patients, followed by the Log- rank test. Results:There were no significant differences in gender, surgical resection range, pathological type, molecular typing, postoperative mutism and M-stage between the 2 groups (all P>0.05). Of 86 patients, the median PFS and OS were 3.0 (0.2-6.3) years, and 3.6 (0.5-6.3) years, respectively.Twenty five cases (29.1%) relapsed, 13 cases (15.1%) died.The 3-year[(65.8±6.8)% vs.(82.0±7.3)%] and 5-year PFS[(56.8±7.7)% vs.(82.0±7.3)%] in non-chemotherapy group were significantly lower than those of chemotherapy group ( P=0.037). The 3-year[(81.6±5.6)% vs.100.0%] and 5-year OS[(71.2±7.7)% vs.(92.3±7.4)%] in non-chemotherapy group were significantly lower than those of chemotherapy group ( P=0.025). Among the children with the SHH subtype, the PFS of children with oral Etoposide maintenance chemotherapy after a regular treatment was significantly higher than that without oral maintenance chemotherapy (100.0% vs.57.1%)( P=0.021). The major adverse events of oral Etoposide were myelosuppression and gastrointestinal symptoms, which were mostly relieved after a symptomatic treatment.Treatment-related deaths were not reported. Conclusions:The prognosis of disseminated MB in children is relatively poor.Oral Etoposide for maintenance therapy after a standard treatment is beneficial in reducing relapse and improving the 5-year survival, which is well tolerated.

Tumor-induced osteomalacia(TIO)is a rare paraneoplastic syndrome in which tumor-induced osteochondrosis is a metabolic bone disease caused by increased renal excretion of phosphorus due to excessive secretion of fibroblast growth factor 23(FGF23)by tumor tissue.We report here a rare case of TIO in which the tumor was found in the hyoid body and the patient had tertiary hyperparathyroidism.The patient's symptoms did not improve after removal of the tumor from the hyoid body,and the patient's hypophosphatemia was gradually improved after subsequent removal of the left parathyroid gland.TIO derived from the tongue tumor is very rare,and also subsequent tertiary hyperparathyroidism is even rarer.This report helps to improve the understanding of TIO and provides reference in the diagnosis and treatment of TIO.

Objective:To investigate the molecular pathogenesis of a newly discovered gene mutation in a family with hereditary coagulation factor Ⅺ(FⅪ) deficiency.Methods:The proband was admitted to the First Affiliated Hospital of Wenzhou Medical University in September 2021 due to "calculus of intrahepatic duct". The patient had no symptoms of spontaneous bleeding.The clinical data and blood samples of the proband and her family members (10 persons in 3 generations) were collected.The activated partial thromboplastin time (APTT) and FⅪ activity (FⅪ:C) were performed by the one-stage clotting assay. FⅪ antigen (FⅪ:Ag) were detected by enzyme linked immunosorbent assay (ELISA). Genomic DNA extracted from peripheral blood cells of subjects was used as template to analyze F11 gene mutation by DNA direct sequencing. Bioinformatics software was used to analyze the effects of mutations on protein structure and function. Wild-type and mutant FⅪ protein expression vectors were constructed and transient transfected into HEK293T cells. The total RNA was extracted from positive transfected cells and then reversely transcribed into cDNA. The mRNA expression level of F11 gene in transfected cells was detected by real-time fluorescence quantitative PCR (qRT-PCR). The content of FⅪ:Ag and the expression of FⅪ protein in transfected cell lysates and culture supernatant were detected by ELISA and western blot.Results:The APTT of the proband was significantly prolonged to 107.9s (reference range 29.0-43.0s), while FⅪ:C and FⅪ:Ag were significantly decreased to 2% (reference range 84%-122%) and 5% (reference range 76%-127%), respectively. Gene sequencing analysis indicated that the proband had c.536C>T (p.Thr161Met) heterozygous missense mutation and c.1556G>A (p.Trp501Ter) heterozygous nonsense mutation in exon 6 and 13 of the F11 gene, respectively. Bioinformatics analysis showed that the amino acids at site 161 of FⅪ protein were threonine (Thr) in the matrix composed of five different species, indicating that Thr161 site was highly conserved among homologous genes in different species. p.Thr161Met heterozygous mutation affected the stability of local intermolecular structure of FⅪ protein. In vitro expression experiments of p.Thr161Met mutation showed that FⅪ protein had a normal synthesis in the cells but secretion dysfunction.Conclusions:c.536C>T (p.Thr161Met) heterozygous missense mutation and c.1556G>A (p.Trp501Ter) heterozygous nonsense mutation were mainly responsible for the decrease of FⅪ in this family. p.Thr161Met mutation was first reported in the world and did not affect the normal synthesis of FⅪ protein, but caused secretion dysfunction.

Objective:Summarizing the clinical characteristics of extraneural metastasis in childhood medulloblastoma.Methods:A total of 616 cases with medulloblastoma treated in Beijing Shijitan Hospital from April 2010 to April 2019 were analyzed retrospectively, among which 11 cases developed extraneural metastasis.The age of onset, location and time of extraneural metastasis, pathological and molecular typing, treatment and prognosis were descriptively analyzed.The differences of blood biochemical indexes between medulloblastoma cases with and without extraneural metastasis were statistically analyzed by t test. Results:As of February 2020, the median follow-up period was 16 months (ranging from 3 to 69 months). Eleven cases, including 8 males and 3 females, were diagnosed with extraneural metastasis, with the incidence being about 1.8%.The median age of medulloblastoma was 6 years (2-10 years), and the median age at presentation of extraneural metastasis was 7 years (2-12 years). Extraneural metastasis occurred from 0.5 months to 38.0 months after the operation, and the affected location includes bone (6 cases), bone marrow (3 cases), lung (3 cases), pelvis (2 cases) and abdominal cavity (1 case). In these patients, the range of lactic dehydrogenase (LDH) was (2 298.00±1 570.70) U/L and neuron-specific enolase (NSE) was (201.00±68.34) μg/L, which were significantly higher than those in patients without extraneural metastasis [(249.50±46.28) U/L and (22.80±7.12) μg/L, all P<0.05]. Partial patients were treated with chemotherapy, while the majority of them were treated with palliative treatment in the terminal stage, with the survival period mostly less than 10 months. Conclusions:Although there is a low incidence of extraneural metastasis in medulloblastoma pediatric patients, the prognosis of these patients with extraneural metastasis is poor and most of them would die within one year.The most common sites include bone, followed by bone marrow and lungs, which may be related to the spread of cerebrospinal fluid and the increased levels of LDH and NSE.