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53. A semimechanistic pharmacokinetic/pharmacodynamic model for alanine aminotransferase‐based hepatotoxicity of methotrexate in paediatric patients with acute lymphoid leukaemia.

Author

Yin, Qiufen, Cheng, Zeneng, Yang, Minghua, Wang, Shengfeng, and Xie, Feifan

Subjects
ALANINE aminotransferase, CHILD patients, ACUTE leukemia, HEPATOTOXICOLOGY, PHARMACOKINETICS, ALANINE, METHOTREXATE
Abstract

Aims: Methotrexate (MTX) is recognized for its potential to induce hepatotoxicity, commonly manifested by elevated alanine aminotransferase (ALT) levels. However, the quantitative relationship between the pharmacokinetics (PK) of MTX and ALT‐based hepatotoxicity remains unclear. This study aimed to develop a semimechanistic PK/pharmacodynamic (PD) model to characterize the MTX‐induced hepatotoxicity based on ALT in paediatric patients with acute lymphoid leukaemia. Methods: A retrospective study was conducted on paediatric patients who received high‐dose (3–5 g/m2) MTX treatment. MTX concentrations were assessed at 24‐h intervals until the concentration dropped below 0.1 μmol/L. ALT concentrations were measured both before and after MTX administration. A population PK model was initially developed, which was later connected to a semimechanistic hepatotoxicity model. Results: The PK model was developed using 354 MTX concentrations obtained from 51 patients, while the PD model was constructed using 379 ALT concentrations collected from 48 patients. The optimal PK model for MTX consisted of a 2‐compartment structure, where body surface area served as a covariate for clearance and central volume of distribution. An indirect response model coupled to a liver injury signal transduction model was developed to describe the dynamics of ALT after MTX administration. The drug effect was adequately described by a linear model, exhibiting considerable interoccasion variability for each treatment session. No significant covariates were identified to have an impact on the PD parameters. Conclusion: A semimechanistic model was developed to describe ALT‐based hepatotoxicity of MTX, and it has the potential to serve as a valuable tool for characterizing drug‐induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

Published
2023
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57. Analyticity and Existence of the Keller–Segel–Navier–Stokes Equations in Critical Besov Spaces

Author

Yang Minghua, Fu Zunwei, and Liu Suying

Subjects
keller–segel system, navier–stokes equation, gevrey regularity, global solution, besov space, 35q30, 35q335, 76d03, 35e15, 42b37, Mathematics, QA1-939
Abstract

This paper deals with the Cauchy problem to the Keller–Segel model coupled with the incompressible 3-D Navier–Stokes equations. Based on so-called Gevrey regularity estimates, which are motivated by the works of Foias and Temam [20], we prove that the solutions are analytic for a small interval of time with values in a Gevrey class of functions. As a consequence of Gevrey estimates, we particularly imply higher-order derivatives of solutions in Besov and Lebesgue spaces. Moreover, we prove that the existence of a positive constant C~{\tilde{C}} such that the initial data (u0,n0,c0):=(u0h,u03,n0,c0){(u_{0},n_{0},c_{0}):=(u_{0}^{h},u_{0}^{3},n_{0},c_{0})} satisfy

Published
2018
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61. Prognostic factors of childhood acute lymphoblastic leukemia with TCF3::PBX1 in CCCG‐ALL‐2015: A multicenter study

Author

Zhang, Honghong, primary, Wan, Yang, additional, Wang, Hongsheng, additional, Cai, Jiaoyang, additional, Yu, Jie, additional, Hu, Shaoyan, additional, Fang, Yongjun, additional, Gao, Ju, additional, Jiang, Hua, additional, Yang, Minghua, additional, Liang, Changda, additional, Jin, Runming, additional, Tian, Xin, additional, Ju, Xiuli, additional, Hu, Qun, additional, Jiang, Hui, additional, Li, Zhifan, additional, Wang, Ningling, additional, Sun, Lirong, additional, Leung, Alex W. K., additional, Wu, Xuedong, additional, Qian, Xiaowen, additional, Qian, Maoxiang, additional, Li, Chi‐kong, additional, Yang, Jun, additional, Tang, Jingyan, additional, Zhu, Xiaofan, additional, Shen, Shuhong, additional, Zhang, Li, additional, Pui, Ching‐Hon, additional, and Zhai, Xiaowen, additional

Published
2023
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66. A guideline on the molecular ecosystem regulating ferroptosis

Author

Dai, Enyong, Chen, Xin, Linkermann, Andreas, Jiang, Xuejun, Kang, Rui, Kagan, Valerian E., Bayir, Hülya, Yang, Wan Seok, Garcia-Saez, Ana J., Ioannou, Maria S., Janowitz, Tobias, Ran, Qitao, Gu, Wei, Gan, Boyi, Krysko, Dmitri V., Zhu, Xiaofeng, Wang, Jiayi, Krautwald, Stefan, Toyokuni, Shinya, Xie, Yangchun, Greten, Florian R., Yi, Qing, Schick, Joel, Liu, Jiao, Gabrilovich, Dmitry I., Liu, Jinbao, Zeh, Herbert J., Zhang, Donna D., Yang, Minghua, Iovanna, Juan, Kopf, Manfred, Adolph, Timon E., Chi, Jen-Tsan, Li, Changfeng, Ichijo, Hidenori, Karin, Michael, Sankaran, Vijay G., Zou, Weiping, Galluzzi, Lorenzo, Bush, Ashley I., Li, Binghui, Melino, Gerry, Baehrecke, Eric H., Lotze, Michael T., Klionsky, Daniel J., Stockwell, Brent R., Kroemer, Guido, and Tang, Daolin

Abstract

Ferroptosis, an intricately regulated form of cell death characterized by uncontrolled lipid peroxidation, has garnered substantial interest since this term was first coined in 2012. Recent years have witnessed remarkable progress in elucidating the detailed molecular mechanisms that govern ferroptosis induction and defence, with particular emphasis on the roles of heterogeneity and plasticity. In this Review, we discuss the molecular ecosystem of ferroptosis, with implications that may inform and enable safe and effective therapeutic strategies across a broad spectrum of diseases.

Published
2024
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67. Cloning of FITM2 gene and investigating its expression levels in Banna miniature inbred pig (Sus scrofa) tissues.

Author

Xu, Taojie, Yang, Minghua, Jian, Zonghui, Pan, Hongbin, Jia, Junjing, and Zhao, Sumei

Subjects
*GENE expression, *MOLECULAR cloning, *WILD boar, *AMINO acid sequence, *GENE expression profiling, *SOMATIC cell nuclear transfer
Abstract

Fat storage-inducing transmembrane protein 2 (FITM2) plays an important role in regulating lipid storage and could be regarded as a candidate gene for intramuscular fat deposition in pigs. The aim of this study was to clone the coding domain sequence (CDS) of FITM2 gene, to compare the nucleotide acid and deduced amino acid sequences between breeds and species, to analyze the structure and characteristics of protein and to detect the expression profile of gene. The results exhibited that the CDS of FITM2 gene was 789 bp in length. The mutation of nucleotide acids led to the mutation of deduced amino acids between Banna miniature inbred pigs and other two breeds (Yorkshire × Landrace pigs and Duroc × (Landrace × Yorkshire) pigs). It was indicated that high identities of nucleotide acid and deduced amino acid sequences between Banna miniature inbred pigs and other species. The deduced amino acids were composed of loops and alpha helices in the structure. FITM2 protein may be a 30 kDa hydrophobic protein with 26 phosphorylation sites and one potential N-glycosylated site. FITM2 gene was widely expressed in various tissues, and the highest expression level was in adipose tissue. [ABSTRACT FROM AUTHOR]

Published
2023
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68. Circadian clock protein Bmal1 accelerates acute myeloid leukemia by inhibiting ferroptosis through the EBF3/ALOX15 axis.

Author

Wang, Dan, Wang, Fenglin, Zhang, Haixia, Chen, Pan, and Yang, Minghua

Abstract

Acute myeloid leukemia (AML) is a major leukemia with high mortality. Ferroptosis is an important regulator of cancers. However, the role of ferroptosis and its regulatory mechanisms in AML remain largely unknown. In this study, we reported elevated brain and muscle ARNT‐Like protein‐1 (Bmal1) expression in AML patients and cell lines, and its upregulation indicated the poor survival of patients. The correlation analysis showed that Bmal1 expression was closely correlated with cytogenetics and the French–American–British subtypes, but was not correlated with age, gender and white blood cells. RSL3 reduced Bmal1 expression in HL‐60 and NB4 cells. Malondialdehyde, total iron, Fe2+, glutathione and lipid peroxidation were examined to evaluate ferroptosis. Overexpression of Bmal1 repressed RSL3‐induced ferroptosis in AML cells. Bmal1 recruited Enhancer of zeste homolog 2 (EZH2) to the Early B cell factor 3 (EBF3) promoter and enhanced its methylation, thus suppressing EBF3 expression. Moreover, the knockdown of Bmal1 sensitized AML cells to RSL3‐induced ferroptosis, and it was counteracted by EBF3 knockdown. Furthermore, EBF3 bound to the Arachidonate 15‐pipoxygenase (ALOX15) promoter to enhance its expression, and overexpression of EBF3 enhanced RSL3‐induced ferroptosis dependent on ALOX5. We established a subcutaneous AML xenograft tumor model and reported that knockdown of Bmal1 and overexpression of EBF3 restrained AML growth by promoting ALOX15‐mediated ferroptosis in vivo. Collectively, Bmal1 inhibits RSL3‐induced ferroptosis by promoting EZH2‐mediated EBF3 methylation and suppressing the expression of EBF3 and ALOX15, thus accelerating AML. [ABSTRACT FROM AUTHOR]

Published
2023
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79. Prognostic significance of steroid response in pediatric acute lymphoblastic leukemia: The CCCG-ALL-2015 study

Author

Chu, Jinhua, primary, Cai, Huaju, additional, Cai, Jiaoyang, additional, Bian, Xinni, additional, Cheng, Yumei, additional, Guan, Xianmin, additional, Chen, Xiaoqian, additional, Jiang, Hua, additional, Zhai, Xiaowen, additional, Fang, Yongjun, additional, Zhang, Lei, additional, Tian, Xin, additional, Zhou, Fen, additional, Wang, Yaqin, additional, Wang, Lingzhen, additional, Li, Hong, additional, Kwan Alex, Leung Wing, additional, Yang, Minghua, additional, Yang, Hanfang, additional, Zhan, Aijun, additional, Wang, Ningling, additional, and Hu, Shaoyan, additional

Published
2022
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85. Extended vincristine and dexamethasone pulse therapy may not be necessary for children with TCF3‐PBX1 positive acute lymphoblastic leukaemia

Author

Wan, Yang, primary, Zhang, Honghong, additional, Zhang, Li, additional, Cai, Jiaoyang, additional, Yu, Jie, additional, Hu, Shaoyan, additional, Fang, Yongjun, additional, Gao, Ju, additional, Jiang, Hua, additional, Yang, Minghua, additional, Liang, Changda, additional, Jin, Runming, additional, Tian, Xin, additional, Ju, Xiuli, additional, Hu, Qun, additional, Jiang, Hui, additional, Li, Hui, additional, Wang, Ningling, additional, Sun, Lirong, additional, Leung, Alex W. K., additional, Wu, Xuedong, additional, Wang, Junxia, additional, Li, Chi‐kong, additional, Yang, Jun, additional, Tang, Jingyan, additional, Shen, Shuhong, additional, Zhai, Xiaowen, additional, Pui, Ching‐Hon, additional, and Zhu, Xiaofan, additional

Published
2022
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91. Prognostic factors of childhood acute lymphoblastic leukemia with TCF3-PBX1 in CCCG-ALL-2015: a multi-center study

Author

Zhang, Honghong, primary, Wan, Yang, additional, Wang, Hongsheng, additional, Cai, Jiaoyang, additional, Yu, Jie, additional, Hu, Shaoyan, additional, Fang, Yongjun, additional, Gao, Ju, additional, Jiang, Hua, additional, Yang, Minghua, additional, Liang, Changda, additional, Jin, Runming, additional, Tian, Xin, additional, Ju, Xiuli, additional, Hu, Qun, additional, Jiang, Hui, additional, Li, Zhifan, additional, Wang, Ningling, additional, Sun, Lirong, additional, Leung, Alex, additional, Wu, Xuedong, additional, Qian, Xiaowen, additional, Qian, Maoxiang, additional, Li, Chi, additional, Yang, Jun, additional, Tang, Jingyan, additional, Zhu, Xiaofan, additional, Shen, Shuhong, additional, Zhang, Li, additional, Pui, Ching-Hon, additional, and Zhai, Xiaowen, additional

Published
2022
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92. Reduced Dose Intensity of Daunorubicin During Remission Induction for Low-Risk Patients With Acute Lymphoblastic Leukemia: A Retrospective Cohort Study of the Chinese Children’s Cancer Group

Author

Zhuang, Yong, primary, Wu, Kefei, additional, Zhu, Xiaofan, additional, Cai, Jiaoyang, additional, Hu, Shaoyan, additional, Gao, Ju, additional, Jiang, Hua, additional, Zhai, Xiaowen, additional, Tian, Xin, additional, Fang, Yongjun, additional, Jin, Runming, additional, Hu, Qun, additional, Jiang, Hui, additional, Wang, Ningling, additional, Sun, Lirong, additional, Leung, Wing Kwan, additional, Yang, Minghua, additional, Pan, Kaili, additional, Wu, Xuedong, additional, Liang, Changda, additional, Shen, Shuhong, additional, Yu, Jie, additional, and Ju, Xiuli, additional

Published
2022
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95. Cerium oxide nanoparticle-loaded polyvinyl alcohol nanogels delivery for wound healing care systems on surgery

Author

Cao, Lianlian, Shao, Guojing, Ren, Fengmei, Yang, Minghua, Nie, Yan, Peng, Qian, and Zhang, Peng

Subjects
Male, Chitosan, Mice, Inbred BALB C, integumentary system, cerium nanogels, Nanogels, wound healing, Cerium, RM1-950, in vivo mouse model, Bandages, Anti-Bacterial Agents, Drug Liberation, Mice, polyvinyl alcohol, Animals, Nanoparticles, Therapeutics. Pharmacology, Particle Size, Research Article
Abstract

This study was designed to establish the composition of wound bandages based on Cerium nanoparticle (CeNP)-loaded polyvinyl alcohol (PVA) nanogels. The CeNP nanogel (Ce-nGel) was fabricated by the fructose-mediated reduction of Cerium oxide solutions within the PVA matrix. The influences of different experimental limitations on PVA nanogel formations were examined. The nanogel particle sizes were evaluated by transmission electron microscopy and determined to range from ∼10 to 50 nm. Additionally, glycerol was added to the Ce-nGels, and the resulting compositions (Ce-nGel-Glu) were coated on cotton fabrics to generate the wound bandaging composite. The cumulative drug release profile of the Cerium from the bandage was found to be ∼38% of the total loading after two days. Additionally, antibacterial efficacy was developed for Gam positive and negative microorganisms. Moreover, we examined in vivo healing of skin wounds formed in mouse models over 24 days. In contrast to the untreated wounds, rapid healing was perceived in the Ce-nGel-Glu-treated wound with less damage. These findings indicate that Ce-nGel-Glu-based bandaging materials could be a potential candidate for wound healing applications in the future.

Published
2021

96. Evaluation of Essential and Toxic Elements in the Blood of 0–14-Year-Old Children in Hunan, China From 2013 to 2019: A Retrospective Analysis

Author

Tan, Shan, primary, Yang, Yang, additional, Chen, Zhiheng, additional, Zhao, Lingling, additional, Yang, Zuocheng, additional, Dai, Hongmei, additional, He, Wei, additional, Jiang, Mei, additional, Yao, Yanhua, additional, Huang, Ke, additional, Li, Liu, additional, Zhu, Pengfei, additional, Xu, Shasha, additional, Zhao, Mingyi, additional, and Yang, Minghua, additional

Published
2022
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