1.Three-dimensional kinematic analysis can improve the efficacy of acupoint selection for post-stroke patients with upper limb spastic paresis: A randomized controlled trial.
Xin-Yun HUANG ; Ou-Ping LIAO ; Shu-Yun JIANG ; Ji-Ming TAO ; Yang LI ; Xiao-Ying LU ; Yi-Ying LI ; Ci WANG ; Jing LI ; Xiao-Peng MA
Journal of Integrative Medicine 2025;23(1):15-24
BACKGROUND:
China is seeing a growing demand for rehabilitation treatments for post-stroke upper limb spastic paresis (PSSP-UL). Although acupuncture is known to be effective for PSSP-UL, there is room to enhance its efficacy.
OBJECTIVE:
This study explored a semi-personalized acupuncture approach for PSSP-UL that used three-dimensional kinematic analysis (3DKA) results to select additional acupoints, and investigated the feasibility, efficacy and safety of this approach.
DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS:
This single-blind, single-center, randomized, controlled trial involved 74 participants who experienced a first-ever ischemic or hemorrhagic stroke with spastic upper limb paresis. The participants were then randomly assigned to the intervention group or the control group in a 1:1 ratio. Both groups received conventional treatments and acupuncture treatment 5 days a week for 4 weeks. The main acupoints in both groups were the same, while participants in the intervention group received additional acupoints selected on the basis of 3DKA results. Follow-up assessments were conducted for 8 weeks after the treatment.
MAIN OUTCOME MEASURES:
The primary outcome was the Fugl-Meyer Assessment for Upper Extremity (FMA-UE) response rate (≥ 6-point change) at week 4. Secondary outcomes included changes in motor function (FMA-UE), Brunnstrom recovery stage (BRS), manual muscle test (MMT), spasticity (Modified Ashworth Scale, MAS), and activities of daily life (Modified Barthel Index, MBI) at week 4 and week 12.
RESULTS:
Sixty-four participants completed the trial and underwent analyses. Compared with control group, the intervention group exhibited a significantly higher FMA-UE response rate at week 4 (χ2 = 5.479, P = 0.019) and greater improvements in FMA-UE at both week 4 and week 12 (both P < 0.001). The intervention group also showed bigger improvements from baseline in the MMT grades for shoulder adduction and elbow flexion at weeks 4 and 12 as well as thumb adduction at week 4 (P = 0.007, P = 0.049, P = 0.019, P = 0.008, P = 0.029, respectively). The intervention group showed a better change in the MBI at both week 4 and week 12 (P = 0.004 and P = 0.010, respectively). Although the intervention group had a higher BRS for the hand at week 12 (P = 0.041), no intergroup differences were observed at week 4 (all P > 0.05). The two groups showed no differences in MAS grades as well as in BRS for the arm at weeks 4 and 12 (all P > 0.05).
CONCLUSION:
Semi-personalized acupuncture prescription based on 3DKA results significantly improved motor function, muscle strength, and activities of daily living in patients with PSSP-UL.
TRIAL REGISTRATION
Chinese Clinical Trial Registry ChiCTR2200056216. Please cite this article as: Huang XY, Liao OP, Jiang SY, Tao JM, Li Y, Lu XY, Li YY, Wang C, Li J, Ma XP. Three-dimensional kinematic analysis can improve the efficacy of acupoint selection for post-stroke patients with upper limb spastic paresis: A randomized controlled trial. J Integr Med. 2025; 23(1): 15-24.
Humans
;
Male
;
Female
;
Middle Aged
;
Acupuncture Points
;
Upper Extremity/physiopathology*
;
Biomechanical Phenomena
;
Single-Blind Method
;
Aged
;
Stroke/therapy*
;
Acupuncture Therapy/methods*
;
Stroke Rehabilitation/methods*
;
Adult
;
Muscle Spasticity/therapy*
;
Paresis/physiopathology*
;
Treatment Outcome
2.Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm.
Xiao-Jie LI ; Le CHANG ; Yang MI ; Ge ZHANG ; Shan-Shan ZHU ; Yue-Xiao ZHANG ; Hao-Yu WANG ; Yi-Shuang LU ; Ye-Xuan PING ; Peng-Yuan ZHENG ; Xia XUE
Journal of Integrative Medicine 2025;23(4):445-456
OBJECTIVE:
Circadian rhythm disruption (CRD) is a risk factor that correlates with poor prognosis across multiple tumor types, including hepatocellular carcinoma (HCC). However, its mechanism remains unclear. This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity.
METHODS:
To quantify CRD, the HCC CRD score (HCCcrds) was developed. Using machine learning algorithms, we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort (n = 369), and the robustness of this method was validated. Furthermore, we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes.
RESULTS:
We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis. The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis, higher pathological grade, and advanced clinical stages, while the CRD-related subtype with low HCCcrds had better clinical outcomes. We also identified novel biomarkers for each subtype, such as nicotinamide n-methyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1.
CONCLUSION
We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers. Within these groups greater HCCcrds was associated with worse prognosis. This approach has the potential to improve prediction of an individual's prognosis, guide precision treatments, and assist clinical decision making for HCC patients. Please cite this article as: Li XJ, Chang L, Mi Y, Zhang G, Zhu SS, Zhang YX, et al. Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm. J Integr Med. 2025; 23(4): 445-456.
Humans
;
Carcinoma, Hepatocellular/pathology*
;
Liver Neoplasms/pathology*
;
Circadian Rhythm/genetics*
;
Prognosis
;
Male
;
Female
;
Biomarkers, Tumor/genetics*
;
Middle Aged
;
Machine Learning
;
Computational Biology
3.Comparative Transcriptomic and Metabolomic Analyses Reveal the Mechanism by Which Foam Macrophages Restrict Survival of Intracellular Mycobacterium Tuberculosis.
Xiao PENG ; Yuan Yuan LIU ; Li Yao CHEN ; Hui YANG ; Yan CHANG ; Ye Ran YANG ; Xuan ZHANG ; An Na JIA ; Yong Bo YU ; Yong Li GUO ; Jie LU
Biomedical and Environmental Sciences 2025;38(7):781-791
OBJECTIVES:
This study aimed to investigate the impact of foam macrophages (FMs) on the intracellular survival of Mycobacterium tuberculosis (MTB) and identify the molecular mechanisms influencing MTB survival.
METHODS:
An in vitro FM model was established using oleic acid induction. Transcriptomic and metabolomic analyses were conducted to identify the key molecular pathways involved in FM-mediated MTB survival.
RESULTS:
Induced FMs effectively restricted MTB survival. Transcriptomic and metabolomic profiling revealed distinct changes in gene and metabolite expression in FMs during MTB infection compared with normal macrophages. Integrated analyses identified significant alterations in the cyclic adenosine monophosphate (cAMP) signaling pathway, indicating that its activation contributes to the FM-mediated restriction of MTB survival.
CONCLUSIONS
FMs inhibit MTB survival. The cAMP signaling pathway is a key contributor. These findings enhance the understanding of the role of FMs in tuberculosis progression, suggest potential targets for host-directed therapies, and offer new directions for developing diagnostic and therapeutic strategies against tuberculosis.
Mycobacterium tuberculosis/physiology*
;
Transcriptome
;
Metabolomics
;
Foam Cells/microbiology*
;
Humans
;
Metabolome
;
Tuberculosis/microbiology*
;
Gene Expression Profiling
4.Effects of Total Intravenous Anesthesia and Inhalational Anesthesia on Postoperative Recovery in Patients Undergoing Transsphenoidal Pituitary Surgery:A Systematic Review.
Yun-Ying FENG ; Yu-Pei ZHANG ; Yue-Lun ZHANG ; Bing XING ; Wei LIAN ; Xiao-Peng GUO ; Lu-Lu MA ; Yu-Guang HUANG
Acta Academiae Medicinae Sinicae 2025;47(3):434-440
Objective To systematically evaluate the effects of total intravenous anesthesia and inhalational anesthesia on postoperative recovery in patients undergoing transsphenoidal pituitary tumor resection.Methods A comprehensive search was conducted in international biomedical databases including Ovid Medline,Embase,CINAHL(EBSCO),Cochrane Library,and Web of Science,from inception to July 4,2023.Additionally,ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing and completed trials.The randomized controlled trials(RCT)comparing total intravenous anesthesia and inhalational anesthesia in patients undergoing transsphenoidal surgery for pituitary tumors were included.The methodological quality of the included studies was evaluated by the Cochrane Collaboration tool.Relevant data were extracted and synthesized for analysis.Results A total of 327 records were identified,of which eight RCTs met the inclusion criteria.Four studies showed that the patients receiving desflurane or sevoflurane anesthesia experienced faster emergence from anesthesia than those receiving propofol.Two studies indicated that patients in the propofol group had lower levels of emergence agitation and a lower incidence of early postoperative nausea and vomiting.The results on postoperative cognitive function were inconsistent across studies.No differences were found between the groups in terms of postoperative complications or overall recovery quality during hospitalization.Conclusions Inhalational anesthesia appears to provide an advantage in promoting faster emergence following transsphenoidal pituitary surgery,whereas total intravenous anesthesia may contribute to smoother and more stable recovery.Further high-quality studies are needed to clarify the effects of different anesthetic techniques on both short- and long-term postoperative recovery.
Humans
;
Anesthesia, Intravenous
;
Pituitary Neoplasms/surgery*
;
Anesthesia, Inhalation
;
Randomized Controlled Trials as Topic
;
Anesthesia Recovery Period
;
Pituitary Gland/surgery*
;
Postoperative Period
5.Guideline for Adult Weight Management in China
Weiqing WANG ; Qin WAN ; Jianhua MA ; Guang WANG ; Yufan WANG ; Guixia WANG ; Yongquan SHI ; Tingjun YE ; Xiaoguang SHI ; Jian KUANG ; Bo FENG ; Xiuyan FENG ; Guang NING ; Yiming MU ; Hongyu KUANG ; Xiaoping XING ; Chunli PIAO ; Xingbo CHENG ; Zhifeng CHENG ; Yufang BI ; Yan BI ; Wenshan LYU ; Dalong ZHU ; Cuiyan ZHU ; Wei ZHU ; Fei HUA ; Fei XIANG ; Shuang YAN ; Zilin SUN ; Yadong SUN ; Liqin SUN ; Luying SUN ; Li YAN ; Yanbing LI ; Hong LI ; Shu LI ; Ling LI ; Yiming LI ; Chenzhong LI ; Hua YANG ; Jinkui YANG ; Ling YANG ; Ying YANG ; Tao YANG ; Xiao YANG ; Xinhua XIAO ; Dan WU ; Jinsong KUANG ; Lanjie HE ; Wei GU ; Jie SHEN ; Yongfeng SONG ; Qiao ZHANG ; Hong ZHANG ; Yuwei ZHANG ; Junqing ZHANG ; Xianfeng ZHANG ; Miao ZHANG ; Yifei ZHANG ; Yingli LU ; Hong CHEN ; Li CHEN ; Bing CHEN ; Shihong CHEN ; Guiyan CHEN ; Haibing CHEN ; Lei CHEN ; Yanyan CHEN ; Genben CHEN ; Yikun ZHOU ; Xianghai ZHOU ; Qiang ZHOU ; Jiaqiang ZHOU ; Hongting ZHENG ; Zhongyan SHAN ; Jiajun ZHAO ; Dong ZHAO ; Ji HU ; Jiang HU ; Xinguo HOU ; Bimin SHI ; Tianpei HONG ; Mingxia YUAN ; Weibo XIA ; Xuejiang GU ; Yong XU ; Shuguang PANG ; Tianshu GAO ; Zuhua GAO ; Xiaohui GUO ; Hongyi CAO ; Mingfeng CAO ; Xiaopei CAO ; Jing MA ; Bin LU ; Zhen LIANG ; Jun LIANG ; Min LONG ; Yongde PENG ; Jin LU ; Hongyun LU ; Yan LU ; Chunping ZENG ; Binhong WEN ; Xueyong LOU ; Qingbo GUAN ; Lin LIAO ; Xin LIAO ; Ping XIONG ; Yaoming XUE
Chinese Journal of Endocrinology and Metabolism 2025;41(11):891-907
Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.
6.Effect of visual deprivation training combined with proprioceptive training on balance in hemiplegic patients af-ter stroke
Panpan SU ; Peng YE ; Qian LU ; Chuan HE ; Xiao LU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(3):254-263
Objective To explore the effect of visual deprivation training combined with proprioceptive training on balance function of hemiplegic patients after stroke.Methods A total of 80 stroke patients with hemiplegia in Jiangsu Shengze Hospital were selected from May,2022 to March,2024,and randomly divided into control group(n=20),proprioceptive training group(n=20),visual de-privation group(n=20)and combined group(n=20).All the groups received routine rehabilitation training,while the proprioceptive training group added proprioceptive training,the visual deprivation group added balance training under visual deprivation,and the combined group added visual deprivation training and proprioceptive training,for four weeks.They were assessed with ProKin Balance Test and Training System,Berg Balance Scale(BBS),10-metre walking test(10MWT),Fugl-Meyer Assessment-Lower Extremities(FMA-LE)and Functional Gait Assessment(FGA)before and after treatment.Results The intra-group effect(F>96.618,P<0.001)and interaction effect(F>5.444,P<0.01)were significant in mean longitudinal velocity and mean horizontal velocity.The intra-group effect(F>177.671,P<0.001),inter-group effect(F>3.761,P<0.05)and interaction effect(F>7.555,P<0.001)were significant in movement el-lipse area and movement length both with eyes open and closed.The intra-group effect(F>221.902,P<0.001)and interaction effect(F>7.586,P<0.001)were significant in the time of 10MWT,and the scores of BBS,FMA-LE and FGA;and the inter-group effect were significant in FGA score(F=5.258,P<0.01).Post Hoc test showed that all the indicators were better in the combined group and the visual deprivation group than in the con-trol group(P<0.05);as well as in the proprioceptive training group than in the control group(P<0.05)except mean longitudinal velocity with eyes open,mean horizontal velocity with eyes closed,and movement length with eyes open;while all the indicators were better in the combined group than both in the visual deprivation group and the proprioceptive training group(P<0.05);there was no significant difference between the visual depriva-tion group and the proprioceptive training group for all the indicators(P>0.05).Conclusion Both visual deprivation training and proprioceptive training can improve balance,lower limb motor function and walking of hemiplegic stroke patients,and the combination is more effective.
7.Triptolide Ameliorates Collagen-Induced Arthritis and Bleomycin-Induced Pulmonary Fibrosis in Rats by Suppressing IGF1-Mediated Epithelial Mesenchymal Transition.
Pei-Pei LU ; Lan YAN ; Qi GENG ; Lin LIN ; Lu-Lu ZHANG ; Chang-Qi SHI ; Peng-Cheng ZHAO ; Xiao-Meng ZHANG ; Jian-Yu SHI ; Cheng LYU
Chinese journal of integrative medicine 2025;31(12):1069-1077
OBJECTIVE:
To investigate the common mechanisms among collagen-induced arthritis (CIA), bleomycin (BLM)-induced pulmonary fibrosis, and CIA+BLM to evaluate the therapeutic effect of triptolide (TP) on CIA+BLM.
METHODS:
Thirty-six male Sprague-Dawley rats were randomly assigned to 6 groups according to a random number table (n=6 per group): normal control (NC), CIA, BLM, combined CIA+BLM model, TP low-dose (TP-L, 0.0931 mg/kg), and TP high-dose (TP-H, 0.1862 mg/kg) groups. The CIA model was induced by intradermal injection at the base of the tail with emulsion of bovine type II collagen and incomplete Freund's adjuvant (1:1), with 200 µL administered on day 0 and a booster of 100 µL on day 7. Pulmonary fibrosis was induced via a single intratracheal injection of BLM (5 mg/kg). The CIA+BLM model combined both protocols, and TP was administered orally from day 14 to 35. After successful modeling, arthritis scores were recorded every 3 days, and pulmonary function was assessed once at the end of the treatment period. Lung tissues were collected for histological analysis (hematoxylin eosin and Masson staining), immunohistochemistry, measurement of hydroxyproline (HYP) content, and calculation of lung coefficient. In addition, HE staining was performed on the ankle joint. Total RNA was extracted from lung tissues for transcriptomic analysis. Differentially expressed genes (DEGs) were compared with those from the RA-associated interstitial lung diseases patient dataset GSE199152 to identify overlapping genes, which were then used to construct a protein-protein interaction network. Hub genes were identified using multiple topological algorithms.
RESULTS:
The successfully established CIA+BLM rat model exhibited significantly increased arthritis scores and severe pulmonary fibrosis (P<0.01). By intersecting the DEGs obtained from transcriptomic analysis of lung tissues in CIA, BLM, and CIA+BLM rats with DEGs from rheumatoid arthritis-interstitial lung disease patients (GSE199152 dataset), 50 upregulated and 44 downregulated genes were identified. Through integrated PPI network analysis using multiple topological algorithms, IGF1 was identified as a central hub gene. TP intervention significantly improved pulmonary function by increasing peak inspiratory flow (P<0.01), and reduced lung index and HYP content (P<0.01). Histopathological analysis showed that TP alleviated alveolar collapse, interstitial thickening, and collagen deposition in the lung tissues (P<0.01). Moreover, TP treatment reduced the expression of collagen type I and α-SMA and increased E-cadherin levels (P<0.01). TP also significantly reduced arthritis scores and ameliorated synovial inflammation (P<0.05). Both transcriptomic and immunohistochemical analyses confirmed that IGF1 expression was elevated in the CIA+BLM group and downregulated following TP treatment (P<0.05).
CONCLUSION
TP exerts protective effects in the CIA+BLM model by alleviating arthritis and pulmonary fibrosis through the inhibition of IGF1-mediated EMT.
Animals
;
Pulmonary Fibrosis/complications*
;
Bleomycin/adverse effects*
;
Phenanthrenes/pharmacology*
;
Male
;
Rats, Sprague-Dawley
;
Diterpenes/pharmacology*
;
Epoxy Compounds/therapeutic use*
;
Arthritis, Experimental/complications*
;
Insulin-Like Growth Factor I/metabolism*
;
Rats
;
Lung/physiopathology*
8.Diagnosis of coronary artery lesions in children based on Z-score regression model.
Yong WANG ; Jia-Ying JIANG ; Yan DENG ; Bo LI ; Ping SHUAI ; Xiao-Ping HU ; Yin-Yan ZHANG ; Han WU ; Lu-Wei YE ; Qian PENG
Chinese Journal of Contemporary Pediatrics 2025;27(2):176-183
OBJECTIVES:
To construct a Z-score regression model for coronary artery diameter based on echocardiographic data from children in Sichuan Province and to establish a Z-score calculation formula.
METHODS:
A total of 744 healthy children who underwent physical examinations at Sichuan Provincial People's Hospital from January 2020 to December 2022 were selected as the modeling group, while 251 children diagnosed with Kawasaki disease at the same hospital from January 2018 to December 2022 were selected as the validation group. Pearson correlation analysis was conducted to analyze the relationships between coronary artery diameter values and age, height, weight, and body surface area. A regression model was constructed using function transformation to identify the optimal regression model and establish the Z-score calculation formula, which was then validated.
RESULTS:
The Pearson correlation analysis showed that the correlation coefficients for the diameters of the left main coronary artery, left anterior descending artery, left circumflex artery, and right coronary artery with body surface area were 0.815, 0.793, 0.704, and 0.802, respectively (P<0.05). Among the constructed regression models, the power function regression model demonstrated the best performance and was therefore chosen as the optimal model for establishing the Z-score calculation formula. Based on this Z-score calculation formula, the detection rate of coronary artery lesions was found to be 21.5% (54/251), which was higher than the detection rate based on absolute values of coronary artery diameter. Notably, in the left anterior descending and left circumflex arteries, the detection rate of coronary artery lesions using this Z-score calculation formula was higher than that of previous classic Z-score calculation formulas.
CONCLUSIONS
The Z-score calculation formula established based on the power function regression model has a higher detection rate for coronary artery lesions, providing a strong reference for clinicians, particularly in assessing coronary artery lesions in children with Kawasaki disease.
Humans
;
Male
;
Female
;
Child, Preschool
;
Child
;
Coronary Artery Disease/diagnostic imaging*
;
Infant
;
Mucocutaneous Lymph Node Syndrome
;
Regression Analysis
;
Coronary Vessels/diagnostic imaging*
;
Echocardiography
;
Adolescent
9.Mediating effect of sleep duration between depression symptoms and myopia in middle school students.
Wei DU ; Xu-Xiang YANG ; Ru-Shuang ZENG ; Chun-Yao ZHAO ; Zhi-Peng XIANG ; Yuan-Chun LI ; Jie-Song WANG ; Xiao-Hong SU ; Xiao LU ; Yu LI ; Jing WEN ; Dang HAN ; Qun DU ; Jia HE
Chinese Journal of Contemporary Pediatrics 2025;27(3):359-365
OBJECTIVES:
To explore the mediating role of sleep duration in the relationship between depression symptoms and myopia among middle school students.
METHODS:
This study was a cross-sectional research conducted using a stratified cluster random sampling method. A total of 1 728 middle school students were selected from two junior high schools and two senior high schools in certain urban areas and farms of the Xinjiang Production and Construction Corps. Questionnaire surveys and vision tests were conducted among the students. Spearman analysis was used to analyze the correlation between depression symptoms, sleep duration, and myopia. The Bootstrap method was employed to investigate the mediating effect of sleep duration between depression symptoms and myopia.
RESULTS:
The prevalence of myopia in the overall population was 74.02% (1 279/1 728), with an average sleep duration of (7.6±1.0) hours. The rate of insufficient sleep was 83.62% (1 445/1 728), and the proportion of students exhibiting depression symptoms was 25.29% (437/1 728). Correlation analysis showed significant negative correlations between visual acuity in both eyes and sleep duration with depressive emotions as measured by the Center for Epidemiologic Studies Depression Scale (with correlation coefficients of -0.064, -0.084, and -0.199 respectively; P<0.01), as well as with somatic symptoms and activities (with correlation coefficients of -0.104, -0.124, and -0.233 respectively; P<0.01) and interpersonal relationships (with correlation coefficients of -0.052, -0.059, and -0.071 respectively; P<0.05). The correlation coefficients for left and right eye visual acuity and sleep duration were 0.206 and 0.211 respectively (P<0.001). Sleep duration exhibited a mediating effect between depression symptoms and myopia (indirect effect=0.056, 95%CI: 0.029-0.088), with the mediating effect value for females (indirect effect=0.066, 95%CI: 0.024-0.119) being higher than that for males (indirect effect=0.042, 95%CI: 0.011-0.081).
CONCLUSIONS
Sleep duration serves as a partial mediator between depression symptoms and myopia in middle school students.
Humans
;
Myopia/etiology*
;
Male
;
Female
;
Depression/physiopathology*
;
Cross-Sectional Studies
;
Sleep
;
Adolescent
;
Students
;
Child
;
Time Factors
;
Sleep Duration
10.Effects of MTHFR and GGH gene polymorphisms on plasma concentrations and toxicity following high-dose methotrexate therapy in children with acute lymphoblastic leukemia.
Lin-Xiao TENG ; Qi AN ; Lei WANG ; Nan WANG ; Qing-Ling KONG ; Rui HAN ; Yuan WANG ; Lu LIU ; Yan WANG ; Shu-Mei XU ; Kun-Peng SHI ; Fang-Shan QIU ; Xi-Xi DU ; Jin-Rui SHI
Chinese Journal of Contemporary Pediatrics 2025;27(7):802-807
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

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