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 explore the molecular pathogenesis of hereditary protein C (PC) deficiency due to a p. Gly86Asp variant of the PROC gene through in vitro expression experiment.Methods:Wild type and Gly86Asp mutant expression plasmids of PC were constructed and respectively transfected into HEK 293FT cells. Total RNA was extracted from the transfected cells, and the expression of PROC gene was determined by quantitative real-time PCR (qRT-PCR). PC antigen (PC: Ag) in the supernatant of cell culture and cell lysate was determined by enzyme-linked immunosorbent assay (ELISA), and the level of PC protein was detected by Western blotting. Results:qRT-PCR has detected no significant difference in the transcription level of wild-type and mutant-type PC. Compared with the wild type, the level of mutant PC: Ag in the supernatant and cell lysate were 81.3%±2.6% and 110.0%±2.8%, respectively. No difference was detected in the molecular weight between the wild-type and mutant-type PC by Western blotting. The PC content of mutant type was higher than wild-type in cell lysate, while the opposite was found with the cell culture supernatant.Conclusion:The impaired secretion by mutant PC may be the molecular mechanism of PC deficiency caused by the p.

Objective:To explore the genetic basis for a patient with factor XIII (FXIII) deficiency.Methods:All exons of the F13A1 and F13B genes were amplified by PCR and sequenced directly. The sequencing was performed with a reverse primer if a variant was found. Conservation of variant site was analyzed by the ClustalX software. Four online bioinformatic software including MutationTaster, PolyPhen-2, PROVEAN and SIFT were used to predict the function of the mutation site. The Swiss-PdbViewer software was applied to analyze the changes in the protein model and intermolecular force. Results:The proband was found to harbor a novel c. 515G>C (p.Arg171Pro) variant of the F13A1 gene. The corresponding amino acid Arg171 is conserved among homologous species. Bioinformatic analysis indicated that Arg171Pro variant may affect the protein function. Protein model analysis showed that in the wild-type, there is one hydrogen bond between Arg171 and Pro27; one hydrogen bond between Arg171 and Thr28; two hydrogen bonds between Arg171 and Glu102. When Arg171 was mutated to Pro171, the three hydrogen bonds between Arg171 and Pro27, Glu102 are all disappeared and formed a new benzene ring which might affect the stability of the protein structure. No variant was found in the F13B gene. Conclusion:The Arg171Pro variant may account for the decreased FXIII level. Above finding has enriched the spectrum of F13A1 gene variants.