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

Aim To study the mechanism of salidro-side combined with rosavin in rats with ischemic stroke.Methods The MCAO rats was established by using thread-embolic method.The rats were divided into the sham group,MCAO group,salidroside com-bined with rosavin group,and positive control group;the drug was given continuously for seven days.Western blot was used to detect apoptosis indicators.Proteomics was used to analyse differential proteins(DEPs).STEP receptor inhibitor was injected into the lateral ventricles,the rats were administered for seven days,then the apoptosis indicators were detected.Re-sults Salidroside combined with rosavin could reduce neurological function scores in MCAO rats and inhibit cell apoptosis.Quantitative proteomics identified 496 DEPs in brain tissue and discovered core proteins STEP,p38,and CRTC1.Salidroside combined with rosavin could promote the STEP and CRTC1 while in-hibiting p38 protein.After treatment with STEP inhibi-tor,those effects were reversed.Conclusion Salidro-side combined with rosavin can inhibit cell apoptosis in MCAO rats,which is closely related to the regulation of the STEP/p38/CRTC1 signaling pathway.

Objective:To analyze the clinical characteristics of frailty in elderly patients with chronic obstructive pulmonary disease (COPD).Methods:COPD patients aged ≥65 years registered in the RealDTC study from June 2023 to March 2024 were included. Demographic data, history of exacerbations in the past year, exposure to risk factors (smoking, biomass fuel exposure, occupational exposure), modified Medical Research Council (mMRC) dyspnea score, COPD Assessment Test (CAT) score, forced expiratory volume in the first second predicted of percentage (FEV 1%pred), forced expiratory volume in one second (FEV 1) to forced vital capacity (FVC), and comorbidities (bronchial asthma, bronchiectasis, pulmonary tuberculosis, cardiovascular disease, diabetes mellitus) were collected. According to Fried′s frailty phenotype, patients meeting any 3 of the 5 criteria were defined as frail and divided into a frailty group and a non-frailty group. Multivariate regression analysis was used to screen the related factors of frailty in elderly COPD patients, and the receiver operating characteristic (ROC) curve was used to calculate the area under the curve (AUC) of related factors for frailty assessment. Results:A total of 496 elderly COPD patients were included, of which 144(29.0%) had comorbid frailty. The frailty group had lower mass body index (BMI), FEV 1%pred, and FEV 1/FVC, higher mMRC and CAT scores, more exacerbations and hospitalizations in the past year (all P<0.001), and higher proportions of patients with junior high school education or below, Global Initiative for Chronic Obstructive Lung Disease (GOLD) group E, and GOLD grades 3 and 4 (all P<0.05). Multivariate regression analysis showed that low education level ( OR=2.117, 95% CI: 1.119-4.003), low BMI ( OR=0.927, 95% CI: 0.867-0.991), GOLD grade 4 ( OR=4.251, 95% CI: 1.477-12.235), high CAT score ( OR=1.174, 95% CI: 1.127-1.224), and high mMRC score ( OR=4.578, 95% CI: 3.364-6.231) were independent risk factors for frailty in elderly COPD patients (all P<0.05). The ROC curve showed that CAT score (AUC=0.78) and mMRC score (AUC=0.81) had the highest AUC for assessing frailty in elderly COPD patients. Conclusions:Elderly COPD patients with frailty have lower BMI, worse lung function, and more severe symptom burden. The results provide clinical reference for the management of frail elderly COPD patients.

Aim To study the effect of p-benzoyl sali-droside(pOBz)on angiogenesis after ischemic stroke and to explore the underlying mechanism.Methods The MCAO model was prepared by suture method.Rats were divided into four groups:sham,MCAO,pOBz administration,and edaravone positive control,treated for seven days.The mNSS was used to assess the neurological impairment.Western blotting was em-ployed to detect CD31,NICD,and Hes-1 protein ex-pression,while immunofluorescence staining was ap-plies to quantify CD31-positive cells in ischemic brain tissue.In vitro an OGD/R model was established in HUVECs.Following treatment with varying pOBz con-centrations(0.01,0.1,1 μmol·L-1),the CCK-8 as-say was uses to measure cell viability,and in vitro tube formation assay was utilized to evaluate angiogenesis.Western blotting was employed again to assess CD31,NICD and Hes-1 protein levels.To further elucidate the mechanism,HUVEC were treated with the Notch inhibitor DAPT prior to grouping and pOBz administra-tion,and the same parameters were evaluated.Results pOBz significantly reduced the mNSS score of MCAO rats,increased CD31-positive cell counts,and upregu-lated CD31,NICD,and Hes-1 protein expression(P＜0.01).In vitro results further showed that pOBz could dose-dependently increase the survival rate and angio-genesis ability of HUVEC induced by OGD/R,and promote CD31,NICD and Hes-1 proteins(P＜0.01),and Notch inhibitor DAPT could reverse the above effects of pOBz.Conclusion pOBz promotes angio-genesis in HUVEC,and its mechanism involves activa-tion of the Notch signaling pathway.

Aim To study the effect of p-benzoyl sali-droside(pOBz)on angiogenesis after ischemic stroke and to explore the underlying mechanism.Methods The MCAO model was prepared by suture method.Rats were divided into four groups:sham,MCAO,pOBz administration,and edaravone positive control,treated for seven days.The mNSS was used to assess the neurological impairment.Western blotting was em-ployed to detect CD31,NICD,and Hes-1 protein ex-pression,while immunofluorescence staining was ap-plies to quantify CD31-positive cells in ischemic brain tissue.In vitro an OGD/R model was established in HUVECs.Following treatment with varying pOBz con-centrations(0.01,0.1,1 μmol·L-1),the CCK-8 as-say was uses to measure cell viability,and in vitro tube formation assay was utilized to evaluate angiogenesis.Western blotting was employed again to assess CD31,NICD and Hes-1 protein levels.To further elucidate the mechanism,HUVEC were treated with the Notch inhibitor DAPT prior to grouping and pOBz administra-tion,and the same parameters were evaluated.Results pOBz significantly reduced the mNSS score of MCAO rats,increased CD31-positive cell counts,and upregu-lated CD31,NICD,and Hes-1 protein expression(P＜0.01).In vitro results further showed that pOBz could dose-dependently increase the survival rate and angio-genesis ability of HUVEC induced by OGD/R,and promote CD31,NICD and Hes-1 proteins(P＜0.01),and Notch inhibitor DAPT could reverse the above effects of pOBz.Conclusion pOBz promotes angio-genesis in HUVEC,and its mechanism involves activa-tion of the Notch signaling pathway.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

Aim To study the mechanism of salidro-side combined with rosavin in rats with ischemic stroke.Methods The MCAO rats was established by using thread-embolic method.The rats were divided into the sham group,MCAO group,salidroside com-bined with rosavin group,and positive control group;the drug was given continuously for seven days.Western blot was used to detect apoptosis indicators.Proteomics was used to analyse differential proteins(DEPs).STEP receptor inhibitor was injected into the lateral ventricles,the rats were administered for seven days,then the apoptosis indicators were detected.Re-sults Salidroside combined with rosavin could reduce neurological function scores in MCAO rats and inhibit cell apoptosis.Quantitative proteomics identified 496 DEPs in brain tissue and discovered core proteins STEP,p38,and CRTC1.Salidroside combined with rosavin could promote the STEP and CRTC1 while in-hibiting p38 protein.After treatment with STEP inhibi-tor,those effects were reversed.Conclusion Salidro-side combined with rosavin can inhibit cell apoptosis in MCAO rats,which is closely related to the regulation of the STEP/p38/CRTC1 signaling pathway.

Objective:To analyze the clinical characteristics of frailty in elderly patients with chronic obstructive pulmonary disease (COPD).Methods:COPD patients aged ≥65 years registered in the RealDTC study from June 2023 to March 2024 were included. Demographic data, history of exacerbations in the past year, exposure to risk factors (smoking, biomass fuel exposure, occupational exposure), modified Medical Research Council (mMRC) dyspnea score, COPD Assessment Test (CAT) score, forced expiratory volume in the first second predicted of percentage (FEV 1%pred), forced expiratory volume in one second (FEV 1) to forced vital capacity (FVC), and comorbidities (bronchial asthma, bronchiectasis, pulmonary tuberculosis, cardiovascular disease, diabetes mellitus) were collected. According to Fried′s frailty phenotype, patients meeting any 3 of the 5 criteria were defined as frail and divided into a frailty group and a non-frailty group. Multivariate regression analysis was used to screen the related factors of frailty in elderly COPD patients, and the receiver operating characteristic (ROC) curve was used to calculate the area under the curve (AUC) of related factors for frailty assessment. Results:A total of 496 elderly COPD patients were included, of which 144(29.0%) had comorbid frailty. The frailty group had lower mass body index (BMI), FEV 1%pred, and FEV 1/FVC, higher mMRC and CAT scores, more exacerbations and hospitalizations in the past year (all P<0.001), and higher proportions of patients with junior high school education or below, Global Initiative for Chronic Obstructive Lung Disease (GOLD) group E, and GOLD grades 3 and 4 (all P<0.05). Multivariate regression analysis showed that low education level ( OR=2.117, 95% CI: 1.119-4.003), low BMI ( OR=0.927, 95% CI: 0.867-0.991), GOLD grade 4 ( OR=4.251, 95% CI: 1.477-12.235), high CAT score ( OR=1.174, 95% CI: 1.127-1.224), and high mMRC score ( OR=4.578, 95% CI: 3.364-6.231) were independent risk factors for frailty in elderly COPD patients (all P<0.05). The ROC curve showed that CAT score (AUC=0.78) and mMRC score (AUC=0.81) had the highest AUC for assessing frailty in elderly COPD patients. Conclusions:Elderly COPD patients with frailty have lower BMI, worse lung function, and more severe symptom burden. The results provide clinical reference for the management of frail elderly COPD patients.

Objective:To investigate the synergistic effect and its mechanism of ginsenoside-Rg5 in combination with imatinib in inhibiting proliferation of chronic myeloid leukemia K562 cells.Methods:K562 cells were treated with ginsenoside-Rg5 and imatinib.Cell survival was detected by CCK-8 assay,and IC50 were calculated separately for each drug.Based on the value of IC50 of ginsenoside-Rg5 and imatinib,an appropriate concentration gradient was selected for the combination.The synergistic effect of the two drug was analyzed using the online software synergy finder.The effects of single or combination therapy on apoptosis rate and the cell cycle distribution of K562 cells were analyzed by flow cytometry.Western blot was used to detect the expression of PI3K/AKT/mTOR signaling pathway related proteins and apoptosis related proteins in K562 cells after single or combination therapy.Results:Ginsenoside-Rg5 and imatinib were able to inhibit the proliferative activity of K562 cells in a dose-dependent manner(r=-0.991,r=-0.942).The synergy score ZIP＞10 was measured by Synergy Finder online software,indicating that ginsenoside-Rg5 and imatinib act synergistically on K562 cells.The apoptotic rates of K562 cells after single treatments with ginsenoside-Rg5 and imatinib were 11.96％and 8.13％,respectively,while the rate increased to 21.35％with the combination of two drugs,the apoptosis rate in the combination group was higher than that in the single-drug group(P＜0.05).The proportion of K562 cells in the G0/G1 phase was significantly increased with the combined treatment of two drugs(P＜0.05).The protein expression levels of p-PI3K,p-AKT,p-mTOR in K562 cells treated with the combination were significantly decreased,with noticeable downregulation of BCL-2 and upregulation of BAX,leading to a decreased Bcl-2/BAX ratio,while no significant changes were observed in the non-phosphorylated forms of PI3K,AKT,and mTOR proteins.Conclusion:The combination of ginsenoside-Rg5 and imatinib can inhibit the proliferation of CML cells and induce apoptosis,and the mechanism may act through PI3K/AKT/mTOR signaling pathways.