OBJECTIVES: To investigate the effects of methylenetetrahydrofolate reductase (MTHFR) rs1801133 and γ-glutamyl hydrolase (GGH) rs11545078 gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate (MTX) therapy in children with acute lymphoblastic leukemia (ALL). METHODS: Children with ALL treated at the Xuzhou Children's Hospital of Xuzhou Medical University from January 2021 to April 2024 were selected for this study. Genotypes of MTHFR rs1801133 and GGH rs11545078 were determined using multiplex polymerase chain reaction. MTX plasma concentrations were measured by enzyme-multiplied immunoassay technique, and toxicity was graded according to the Common Terminology Criteria for Adverse Events version 5.0. The relationships between MTHFR rs1801133 and GGH rs11545078 genotypes and both MTX plasma concentrations and associated toxicities were analyzed. RESULTS: In the low-risk ALL group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 72 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05), and the GGH rs11545078 genotype was associated with increased MTX plasma concentrations at 48 hours (P<0.05). In the intermediate- to high-risk group, the MTHFR rs1801133 genotype was associated with the occurrence of reduced hemoglobin (P<0.05), and the GGH rs11545078 genotype was associated with the occurrence of thrombocytopenia (P<0.05). CONCLUSIONS Detection of MTHFR rs1801133 and GGH rs11545078 genotypes can be used to predict increased MTX plasma concentrations and the occurrence of toxic reactions in high-dose MTX treatment of ALL, enabling timely interventions to enhance safety.
Humans ; Methotrexate/toxicity* ; Methylenetetrahydrofolate Reductase (NADPH2)/genetics* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood* ; Male ; Female ; Child ; Child, Preschool ; gamma-Glutamyl Hydrolase/genetics* ; Antimetabolites, Antineoplastic/adverse effects* ; Infant ; Polymorphism, Genetic ; Adolescent ; Genotype ; Polymorphism, Single Nucleotide

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

This study was aimed at identifying the pathogenic bacteria responsible for the death of a young tiger at the Fujian Meihua Mountain South China Tiger Breeding Research Institute.Tissue samples from the lungs,liver,and intestines of the deceased tiger were collected,and the bacteria were cultured inasterile environment.The bacterial strains were characterized according to their morphological and molecular biological properties,including assessment of virulence genes and antibiotic resistance genes,mouse lethality tests,and antibiotic susceptibility evaluations.A predominant bacterial strain isolated from the liver of the deceased tiger was identified as enterotoxigenic Escherichia coli(ETEC)strain Tiger22513F.Phylogenetic analysis of the 16S rRNA gene revealed that the Tiger22513F strain exhibited close genetic similarity to the reference strain ETEC(MF919609.1),with 99.9%nucleotide similarity,and resided on the same evolutionary branch.The Tiger22513F strain contained 11 antibiotic resistance genes(tetA,sul1,sul3,cmlA,floR,blaTEM,blaSHV,blaCMY-2,qnrA,qnrS,and qnrD)along with five virulence genes(VT1,fyuA,tsh,iucD,and ST).Mouse lethality tests indicated significant pathogenicity toward mice,affecting primarily the lungs,liver,and intestines.Antibiotic susceptibility testing demonstrated that this strain exhibited resistance to various classes of beta-lactam antibiotics,as well as quinolones and aminoglycosides.This investigation successfully isolated a multi-drug resistant enterotoxigenic Escherichia coli strain with pronounced pathogenicity from the liver of a deceased tiger;thus providing valuable scientific insights for clinical diagnosis,as well as prevention and control measures,against ETEC infections in South China tigers.

The scientific research and innovation capabilities of medical students are intrinsically linked to the sustained and high-quality development of national healthcare initiatives.Cultivating outstanding medi-cal students with independent scientific capabilities and innovative consciousness is a critical component in the education and training of high-level medical professionals.Our investigation revealed that within the imperfections of the cultivating model,some faculty and students at medical schools have an insufficient understanding of scientific research and innovation and lack motivation for engaging in such activities,which hinder the progression of scientific research activities.Consequently,we initiated a teaching practice and exploratory study on the"tutorial system"aimed at fostering medical students'scientific research and innovation abilities.Based on the principle of"research informing teaching,teaching and research advan-cing together,"this study implements a"tutorial system"coordinated by tutors,supplemented by graduate and undergraduate student mentors,to cultivate innovative thinking,stimulate interest in scientific re-search,and enhance practical and research skills among medical students.Through collaborative efforts within"scientific research innovation teams,"various educational methods—including preliminary re-search,in-class and extracurricular activities,intra-group and inter-group interactions,and theoretical and practical applications—are employed to improve and strengthen the cultivation of medical students'scientif-ic research and innovation abilities.This study aims to provide valuable references for optimizing medical education management systems and enhancing the quality of medical student training.

Objective:To investigate the positive rate and isolate Bordetella pertussis in children with suspected whooping cough and their close family members in Zhejiang Province, and further explore the susceptibility and resistant mechanism of Bordetella pertussis to antibiotics. Methods:A total of 273 nasopharynx swabs specimens from children with suspected whooping cough in Hangzhou Children′s Hospital from May 2022 to October 2022 were collected. The strains were isolated and cultured using charcoal select agar plate. Pertussis target genes were detected by RT-PCR. E-test method was used to detect the sensitivity of Bordetella pertussis strains to different antibiotics. The mechanism of resistance of Bordetella pertussis to macrolides was analyzed by whole genome sequencing. The phylogenetic analysis of isolated strains was based on core genome multilocus sequence typing(cgMLST). Results:Among 273 clinical samples of children with suspected pertussis and their close family members, 168 samples were positive by fluorescence quantitative PCR, accounting for 61.54%, and 30 pertussis strains were successfully isolated with a positive rate of 10.98%. In addition, among the 143 samples of close family members, 54.55% (78/143) samples were positive by RT-PCR and 9.79% (14/143) samples were positive by culture, suggesting that the close family member are important in family transmission of pertussis. Besides, most of the positive samples were from mothers. The results of E-test showed that 96.67%(29/30) strains showed high resistance to azithromycin with MIC value>256 mg/L, and the resistant mechanism of azithromycin was A2047G mutation in 23S rRNA. The phylogenetic analysis based on the cgMSLT showed that the isolated strains were clustered into two new different clades.Conclusions:The positive rate of Bordetella pertussis in close family members is at a high level and the mother may be the main source of infection, which is of great significance for monitoring and laboratory detection of suspected children′s family members. Bordetella pertussis shows high resistance to macrolides in Zhejiang Province, so monitoring of the antimicrobial resistance should be further strengthened to provide theoretical basis for clinical treatment and drug guidance.

Objective To investigate the values of CT radiomics combined with machine learning algorithms for discriminating tumor deposits(TDs),lymph node metastasis(LNM)and their simultaneous occurrence in colorectal cancer(CRC).Methods Totally 261 CRC patients treated at some hospital from January 2017 to December 2023 had their clinical data analyzed retrospectively,who were classified into a TDs-positive group(TDs+group,64 cases),a LNM-positive group(LNM+group,99 cases)and a TDs-positive combined with LNM-positive group(TDs+combined with LNM+group,98 cases)according to A JCC 8th Edition:Colorectal Cancer.MaZda version 4.6 software was used to outline the region of interest,and then the texture feature parameters with the most discriminative value were selected by the screening method coming with this software.Texture feature parameters with statistically significant differences in one-way analysis(P＜0.05)were included to draw ROC curves,and the diagnostic efficacy of the included parameters was evaluated.The diagnostic efficacy of four machine learning algorithms such as Bayesian,decision tree,random forest and Logistic regression for the TDs+group,the LNM+group and the TDs+combined with LNM+group was assessed based on the included parameters and ten-fold cross-validation.Statistical analysis was performed using SPSS 26.0,MedCalc 19.1.3,Weka 3.8.6 and R language software.Results Texture feature parameters with statistically significant(P＜0.05)one-way ANOVA differences among the 3 groups included skewness,S(2,-2)and mean value,S(0,4)correlation,S(3,3)difference variance and S(0,4)inverse moments.The S(3,3)difference variance had the highest diagnostic efficacy in the TDs+group and the LNM+group,and the skewness did in the TDs+combined with LNM+group.Random forest algorithm behaved the best in diagnostic efficacy when compared with Bayesian,decision tree and Logistic regression algorithms,which had the accuracy rates being 0.897,0.830 and 0.861 and the AUCs being 0.951,0.957 and 0.958 respectively in the TDs+group,the LNM+group and the TDs+combined with LNM+group.Conclusion CT radiomics combined with random forest algorithm is of high value for discriminating TDs,LNM and their simultaneous occurrence in CRC patients,and thus can provide comprehensive diagnosis information for clinicians and help to formulate accurate treatment strategies for patients.[Chinese Medical Equipment Journal,2024,45(11):60-66]

Objective Hippocampal atrophy is a clinically important marker for the diagnosis of many psychiatric disorders such as Alzheimer’s disease‚ so accurate segmentation of the hippocampus is an important scientific issue. With the development of deep learning‚ a large number of advanced automatic segmentation method have been proposed. However‚ 3D hippocampal segmentation is still challenging due to the effects of various noises in MRI and unclear boundaries between various classes of the hippocampus. Therefore‚ the aim of this paper is to propose new method to segment the hippocampal head‚ body‚ and tail more accurately. Methods To overcome these challenges‚ this paper proposed two strategies. One was the spatial and frequency domain features adaptive fusion strategy‚ which reduced the influence of noise on feature extraction by automatically selecting the appropriate frequency combination through fast Fourier transform and convolution. The other was an inter-class boundary region enhancement strategy‚ which allowed the network to focus on learning the boundary regions by weighting the loss function of the boundary regions between each class to achieve the goal of pinpointing the boundaries and regulating the size of the hippocampal head‚ body and tail. Results Experiments performed on a 50-case teenager brain MRI dataset show that our method achieves state-of-the-art hippocampal segmentation. Hippocampal head‚ body and tail had been improved compared to the existing method. Ablation experiments demonstrated the effectiveness of our two proposed strategies‚ and we also validated that the network had a strong generalization ability on a 260-case Task04_Hippocampus dataset. It was shown that the method proposed in this paper could be used in more hippocampal segmentation scenarios. Conclusion The method proposed in this paper can help clinicians to observe hippocampal atrophy more clearly and accomplish more accurate diagnosis and follow-up of the condition.

Objective:This study aimed to clarify the clinical characteristics of children infected with rhinovirus in the context of the Corona Virus Disease 2019 (COVID-19) pandemic and to explore the impact of recent COVID-19 infection history on their clinical features.Methods:Clinical data and laboratory test result of 286 children diagnosed with rhinovirus infection at Hangzhou Children′s Hospital from July 2022 to October 2023 were collected. A retrospective survey was conducted to determine whether all study participants had a history of COVID-19 infection within the 6 months prior to hospitalization.Results:Among the 286 children with rhinovirus infection, 180 (62.94%) had simple rhinovirus infection, while 106 (37.06%) had co-infections with other pathogens; Among the 180 rhinovirus simplex-positive children, 56.67% had wheezing symptoms; among them, 15 cases (15/180, 8.33%) were diagnosed with acute asthma attacks; 7 cases (7/180, 3.88%) were diagnosed with severe pneumonia. Based on whether the children had a history of COVID-19 infection in the 6 months prior to hospitalization, they were divided into a group with previous COVID-19 infection and a group without previous COVID-19 infection. There were no significant differences between the two groups in terms of gender, age of onset, peak fever, incidence of wheezing, incidence of pneumonia, proportion of severe pneumonia, proportion of severe asthma attacks, duration of fever, time to relief of wheezing, length of stay, white blood cell count, eosinophil count, C-reactive protein, procalcitonin, immunoglobulin E, oxygen therapy requirements, and use of intravenous steroids ( P>0.05). Conclusions:A history of COVID-19 infection in the past 6 months does not exacerbate the clinical symptoms of children with rhinovirus infection, nor does it increase the incidence of wheezing.

This study was aimed at exploring the infections and viral genetic characteristics in rodents from coastal cities in Fujian Province.Intestinal tissue samples were obtained from rodents in Ningde,Fuzhou,Quanzhou,and Zhangzhou city.The adenovirus DNA polymerase(DPOL)gene was analyzed by nested PCR,and the large(L)segment gene of arenavirus was as-sessed with RT-PCR.Homology and genetic characteristics were analyzed in bioinformatics software.A total of 152 rodents were captured and showed a murine adenovirus infection rate of 4.61％.The murine adenovirus infection rate was 5.26％in wild rodents and 4.21％in domestic rodents.Murine adenoviruses were detected in four rodent species:Rattus sladeni,Rattus nor-vegicus,Rattus tanezumi,and Rattus losea.This was the first time that murine adenovirus has been detected in Rattus slade-ni.Analysis of relevant factors revealed no significant differences in murine adenovirus infection rates by rodent species,sex,age,and habitat.Sequence analysis indicated that the adenoviruses infecting rodents in coastal cities of Fujian were Murine ade-novirus 2 and Murine adenovirus 3.A significant difference was observed in the sequences of murine adenoviruses with respect to those in other regions,with nucleic acid sequence identity ranging from 72.25％to 91.01％.No arenavirus was detected in any rodent specimens.Adenovirus infections were found in rodents in coastal cities of Fujian Province,but no arenavirus infec-tions were found.This study provides useful information to support further research on murine adenovirus and arenavirus in Fujian Province.