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

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.

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: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 assess the feasibility of nuclear score combined with cyclin D1 immunocytochemistry in classifying indeterminate thyroid nodules with fine-needle aspiration (FNA) cytological diagnosis of Bethesda category Ⅲ-Ⅴ. Methods: A consecutive cohort of 118 thyroid FNA specimens with indeterminate diagnosis (TBSRTC category Ⅲ-Ⅴ) and available histopathologic follow-up data were collected between December 2018 and April 2022 at the Department of Pathology, Beijing Hospital, China. These cases were subjected to cytological evaluation and cyclin D1 immunocytochemistry. The optimal cut-off points of a simplified nuclear score and the percentage of cyclin D1-positive cells for the diagnosis of malignancy or low-risk neoplasm were determined using the receiver operating characteristic (ROC) curves and area under the ROC curve (AUC). The specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of nuclear score and cyclin D1 immunostaining were evaluated from the crosstabs based on cut-off points. The diagnostic accuracy of simplified nuclear score combined with cyclin D1 immunostaining was estimated using ROC curve analysis. Results: Nuclear grooves, intra-nuclear inclusions and chromatin clearing were more commonly found in malignancy/low-risk neoplasms than benign lesions (P=0.001, P=0.012 and P=0.001 respectively). A cut-off point of≥2 for the simplified nuclear score was sensitive for defining malignancy/low-risk neoplasm, and its PPV, NPV, sensitivity and specificity were 93.6%, 87.5%, 99.0% and 50.0% respectively. A positive cut-off point of 10% positive thyroid cells in cyclin D1 immunostaining demonstrated sensitivity of 88.5%, specificity of 100%, PPV of 100% and NPV of 53.8% for correctly detecting thyroid malignancy or low-risk neoplasm. The sensitivity and PPV of simplified nuclear score combined with cyclin D1 immunostaining were 93.3% and 100%, respectively. Both specificity and NPV were maintained at high levels (100% and 66.7%, respectively). The diagnostic accuracy of simplified nuclear score combined with cyclin D1 immunostaining in detecting thyroid malignancy/low-risk neoplasm was increased to 94.1% compared to using either of them alone. Conclusions: Combing simplified nuclear score and cyclin D1 immunostaining on FNA cytology specimens can increase the diagnostic accuracy in classifying thyroid nodules of indeterminate cytological categories. Thus, this supplementary approach provides a simple, accurate, and convenient diagnostic method for cytopathologists so that may reduce unnecessary thyroidectomies.
Humans ; Thyroid Nodule/pathology* ; Biopsy, Fine-Needle ; Cyclin D1 ; Immunohistochemistry ; Thyroid Neoplasms/pathology* ; Retrospective Studies

The aim of this study is to investigate the effects of Gynostemma pentaphyllum dried with two different methods(air drying and heating) on inflammation in acute lung injury(ALI) mice in vivo and in vitro. Lipopolysaccharide(LPS) was sprayed into the airway of wild type C57BL/6J male mice to establish the model, and the drug was injected into the tail vein 24 h after modeling. Lung function, lung tissue wet/dry weight(W/D) ratio, the total protein concentration, interleukin 6(IL-6), IL-1β, and tumor necrosis factor-α(TNF-α) in the bronchoalveolar lavage fluid(BALF), and pathological changes of the lung tissue were used to evaluate the effects of different gypenosides on ALI mice. The results showed that total gypenosides(YGGPs) and the gypenosides substituted with one or two glycosyl(GPs_(1-2)) in the air-dried sample improved the lung function, significantly lowered the levels of IL-1β and TNF-α in BALF, and alleviated the lung inflammation of ALI mice. Moreover, GPs_(1-2) had a more significant effect on inhibiting NO release in RAW264.7 cells. This study showed that different drying methods affected the anti-inflammatory activity of G. pentaphyllum, and the rare saponins in the air-dried sample without heating had better anti-inflammatory activity.
Male ; Mice ; Animals ; Tumor Necrosis Factor-alpha/metabolism* ; Gynostemma ; Mice, Inbred C57BL ; Lung ; Anti-Inflammatory Agents/metabolism* ; Interleukin-6/metabolism* ; Interleukin-1beta/metabolism* ; Lipopolysaccharides/pharmacology*

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Objective To study the biomechanical effect of jumping distance on dental implants with socket-shield technique (SST), so as to provide references for clinical standards of jump distance. Methods Based on clinical characteristics, four groups of three-dimensional (3D) SST implant system models with 0, 0. 5, 1 and 1. 5 mm jumping distance were established, and the corresponding material parameters were assigned. The peak stress and stress distributions on models were simulated under specific occlusal condition. Results When the jumpingdistance was non-zero, namely, the implant was not in contact with the retained root fragment, the stress of the implant and abutment increased with the increase of jumping distance, and the peak stress in root fragment and periodontal membrane decreased with the increase of jumping distance. When the jumping distance was zero, the peak stress of the implant, abutment, root fragment and periodontal membrane reached the maximum, far exceeding that of the other groups. Conclusions The jumping distance has a significant effect on the SST implant system. It is recommended to take a larger jumping distance in clinical practices. The edge of the root fragment should be rounded, and the size of the lower edge should not be too small.