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A novel coumarin derivative DBH2 inhibits proliferation and induces apoptosis of chronic myeloid leukemia cells

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Genes & Diseases 2023年第2期10卷 596-607页

作者： Jiajia Xin huijie Zhang Dandan Yin Ning An Yaozhen Chen Jinmei Xu Jing Zhang Zhixin Liu Yongsheng Liu Wen Yin Mingkai Li xingbin hu Department of Blood Transfusion Xijing HospitalAir Force Medical UniversityXi’anShaanxi 710032China Key Laboratory of Biochemistry and Molecular Pharmacology of Chongqing Chongqing Medical UniversityChongqing 400016China Department of Hematology Tangdu HospitalAir Force Medical UniversityXi’anShaanxi 710038China Department of Pharmacology School of PharmacyAir Force Medical UniversityXi’anShaanxi 710032China

With the development of tyrosine kinase inhibitor(TKI)resistance,finding the novel effective chemotherapeutic agent is of seminal importance for chronic myelogenous leukemia(CML)treatment.This study aims to find the effective anti-leukemic candidates and investigate the possible underlying mechanism.We synthesized the novel coumarin derivatives and evaluated their anti-leukemic activity.Cell viability assay revealed that compound DBH2 exhibited the potent inhibitory activity on the proliferation of CML K562 cells and TKI resistant K562 cells.Morphological observation and flow cytometry confirmed that DBH2 could selectively induce cell apoptosis and cell cycle arrest at G2/M phase of the K562 cells,which was further confirmed on the bone marrow cells from CML transgenic model mice and CD34+bone marrow leukemic cells from CML patients.Treatments of DBH2 in combination with imatinib could prolong the survival rate of SCL-tTA-BCR/ABL transgenic model mice significantly.Quantitative RT-PCR revealed that DBH2 inhibited the expression of STAT3 and STAT5 in K562 cells,and caspase-3 knockout alleviated the DBH2 induced apoptosis.Furthermore,DBH2 could induce the expression of PARP1 and ROCK1 in K562 cells,which may play the important role in caspase-dependent apoptosis.Our results concluded that coumarin derivative DBH2 serves as a promising candidate for the CML treatment,especially in the combination with imatinib for the TKI resistant CML,and STAT/caspase-3 pathway was involved in the molecular mechanism of anti-leukemic activity of DBH2.

关键词： Apoptosis Caspase Chronic myeloid leukemia Coumarin STAT

Glutamine metabolic microenvironment drives M2 macrophage polarization tomediate trastuzumab resistance in HER2-positive gastric cancer

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Cancer Communications 2023年第8期43卷 909-937页

作者： xingbin hu Zhenfeng Ma Beibei Xu Shulong Li Zhiqi Yao Bishan Liang Jiao Wang Wangjun Liao Li Lin Chunling Wang Siting Zheng Qijing Wu Qiong huang Le Yu Fenghua Wang Min Shi Department of Oncology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdongP.R.China School of Biomedical Engineering Southern Medical UniversityGuangzhouGuangdongP.R.China School of Pharmaceutical Sciences Southern Medical UniversityGuangzhouGuangdongP.R.China Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongP.R.China

Background:Trastuzumab is a first-line targeted therapy for human epidermal growth factor receptor-2(HER2)-positive gastric cancer.However,the inevitable occurrence of acquired trastuzumab resistance limits the drug benefit,and there is currently no effective reversal measure.Existing researches on the mechanism of trastuzumab resistance mainly focused on tumor cells themselves,while the understanding of the mechanisms of environment-mediated drug resistance is relatively lacking.This study aimed to further explore the mechanisms of trastuzumab resistance to identify strategies to promote survival in these patients.Methods:Trastuzumab-sensitive and trastuzumab-resistant HER2-positive tumor tissues and cells were collected for transcriptome sequencing.Bioinformatics were used to analyze cell subtypes,metabolic pathways,and molecular signaling pathways.Changes in microenvironmental indicators(such as macrophage,angiogenesis,and metabolism)were verified by immunofluorescence(IF)and immunohistochemical(IHC)analyses.Finally,a multi-scale agent-based model(ABM)was constructed.The effects of combination treatment were further validated in nude mice to verify these effects predicted by the ABM.Results:Based on transcriptome sequencing,molecular biology,and in vivo experiments,we found that the level of glutamine metabolism in trastuzumabresistant HER2-positive cells was increased,and glutaminase 1(GLS1)was significantly overexpressed.Meanwhile,tumor-derived GLS1 microvesicles drove M2macrophage polarization.Furthermore,angiogenesis promoted trastuzumab resistance.IHC showed high glutamine metabolism,M2 macrophage polarization,and angiogenesis in trastuzumab-resistant HER2-positive tumor tissues from patients and nudemice.Mechanistically,the cell division cycle 42(CDC42)promoted GLS1 expression in tumor cells by activating nuclear factor kappa-B(NF-κB)p65 and drove GLS1microvesicle secretion through IQmotif-containing GTPase-activating protein 1(IQGAP1).Based on the ABM and in vivo experiments,we confirmed that the combin

关键词： Gastric cancer glutamine metabolism macrophage mathematical model microvesicles trastuzumab

历版《中华人民共和国药典》酊剂制剂通则与中药酊剂相关问题的分析及探讨

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中华中医药杂志 2024年第1期39卷 417-424页

作者：朱荣玥蔡梦如付婷婷胡雪凌王开心尹东阁胡盼祥杨玉畅黄华婷尹兴斌倪健北京中医药大学中药学院北京102488 中药制药与新药开发教育部工程研究中心北京100029 北京市药品检验研究院国家药品监督管理局中成药质量评价重点实验室北京100022

《中华人民共和国药典》(以下简称《中国药典》)是国家药品标准的重要组成部分,其颁布实施对保障药品质量、维护公众健康、促进医药产业发展有着深远的影响。酊剂是中药剂型中重要的组成部分,自1953年起就被药典收录,常用于止痛、健脾... 详细信息

《中华人民共和国药典》(以下简称《中国药典》)是国家药品标准的重要组成部分,其颁布实施对保障药品质量、维护公众健康、促进医药产业发展有着深远的影响。酊剂是中药剂型中重要的组成部分,自1953年起就被药典收录,常用于止痛、健脾益胃等。本研究围绕《中国药典》中酊剂的相关规定进行了整理分析,比较历版《中国药典》中酊剂通则的变化,汇总了从1953年版至2020年版被《中国药典》收录过的26种中药酊剂,从品种、浓度规定、注意事项等方面进行分析比较,探讨其变化及存在的问题;围绕2020年版《中国药典》收录的13种中药酊剂品种,整理分析各品种在不同版本《中国药典》中规定的异同点,从处方及制法、鉴别及含量测定、检查项等方面探讨其变化及发展,分析问题并提出可行性建议,以期为2025年版《中国药典》中药酊剂相关规定的完善提供借鉴和参考。

关键词：《中华人民共和国药典》中药酊剂制剂通则品种主治标准与规定

基于Kokkos模板元编程的性能可移植求解器开发

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数据与计算发展前沿 2024年第1期6卷 12-20页

作者：郑亮黎坤运周兴彬李永辉于要杰向玉开胡健柴华郭黎国家超级计算成都中心四川成都610213 成都数据集团四川成都610041

【目的】解决面向多样化异构计算架构的求解器应用编程问题。【应用背景】超级计算机的硬件架构日益多样化,新的异构架构因生态不够完善,往往导致软件移植研发门槛过高、研发周期过长,以及存在针对不同硬件反复适配、移植等问题。【方... 详细信息

【目的】解决面向多样化异构计算架构的求解器应用编程问题。【应用背景】超级计算机的硬件架构日益多样化,新的异构架构因生态不够完善,往往导致软件移植研发门槛过高、研发周期过长,以及存在针对不同硬件反复适配、移植等问题。【方法】在Kokkos代数算子库基础上,开发一套面向国产E级计算环境的“性能可移植”模板元接口开源框架,用于线性代数求解器编程。【结果】本文给出其用于Krylov子空间算法的简单编程示范,实现了面向国产异构处理器的线性代数求解器移植,部分求解器相较于10核超线程Xeon CPU有数十倍以上加速。【结论】性能可移植编程可成为应对多样化异构计算的解决方案。

关键词：性能可移植 Kokkos 模板元编程线性代数求解器

华蟾素联合沙利度胺/地塞米松方案治疗新诊断多发性骨髓瘤痰瘀痹阻型患者的回顾性临床研究

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中医杂志 2024年第1期65卷 72-78页

作者：张玮光丁海花陈碧清孔祥图代兴斌徐祖琼杨箐刘细细黎陈铖胡中晓朱学军南京中医药大学附属医院江苏省南京市210029 南京中医药大学第一临床医学院南京市浦口区中医院

目的观察华蟾素片联合沙利度胺/地塞米松(TD)方案治疗新诊断多发性骨髓瘤痰瘀痹阻型患者的疗效及安全性。方法回顾性分析2015年6月1日至2019年7月31日江苏省中医院收治的50例新诊断多发性骨髓瘤痰瘀痹阻型患者的临床资料,根据治疗方... 详细信息

目的观察华蟾素片联合沙利度胺/地塞米松(TD)方案治疗新诊断多发性骨髓瘤痰瘀痹阻型患者的疗效及安全性。方法回顾性分析2015年6月1日至2019年7月31日江苏省中医院收治的50例新诊断多发性骨髓瘤痰瘀痹阻型患者的临床资料,根据治疗方案分为对照组(含硼替佐米/地塞米松方案) 27例和观察组(华蟾素片联合TD方案) 23例。两组患者均治疗2或3个疗程。主要结局指标为患者治疗后临床缓解情况(包括总缓解率、深度缓解率),患者1年、2年总生存率,不良反应。次要结局指标为治疗前后骨髓浆细胞比例,血红蛋白、血清β2-微球蛋白、乳酸脱氢酶、血肌酐、血尿素氮水平及骨痛积分、卡氏(KPS)评分。结果治疗后观察组和对照组总缓解率分别为69.57%(16/23)及70.37%(19/27),深度缓解率分别为56.52%(13/23)及55.56%(15/27),两组比较差异均无统计学意义(P>0.05)。观察组和对照组1年总生存率分别为90.9%和92.4%,2年总生存率分别为81.8%和80.9%,组间差异均无统计学意义(P>0.05)。治疗过程中,两组均未发生肾功能损伤。观察组周围神经损伤发生率为8.70%(2例),低于对照组的48.15%(13例),两组比较差异有统计学意义(P<0.01)。与治疗前比较,两组患者治疗后骨髓浆细胞比例、β2-微球蛋白水平、血肌酐水平、骨痛评分降低,血红蛋白水平、KPS评分升高(P<0.05或P<0.01)。两组治疗后比较,观察组治疗后骨痛评分低于对照组,KPS评分高于对照组(P<0.05)。结论华蟾素片联合TD方案与含硼替佐米/地塞米松方案治疗新诊断多发性骨髓瘤痰瘀痹阻型患者疗效相当,但华蟾素片联合TD方案在减轻患者疼痛、提高生活质量方面优于含硼替佐米/地塞米松方案,且安全性更好。

关键词：多发性骨髓瘤痰瘀痹阻华蟾素沙利度胺硼替佐米临床缓解生存率不良反应

Variation in assimilable organic carbon formation during chlorination of Microcystis aeruginosa extracellular organic matter solutions

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Journal of Environmental Sciences 2016年第7期28卷 1-6页

作者： xingbin Sun Ting Yuan huishan Ni Yanpeng Li Yang hu Department of Environmental Science Northeast Forestry University

This study investigated the chlorination of Microcystis aeruginosa extracellular organic matter（EOM） solutions under different conditions, to determine how the metabolites produced by these organisms affect water safety and the formation of assimilable organic carbon（AOC）. The effects of chlorine dosages, coagulant dosage, reaction time and temperature on the formation of AOC were investigated during the disinfection of M.aeruginosa metabolite solutions. The concentration of AOC followed a decreasing and then increasing pattern with increasing temperature and reaction time. The concentration of AOC decreased and then increased with increasing chlorination dosage, followed by a slight decrease at the highest level of chlorination. However, the concentration of AOC decreased continuously with increasing coagulant dosage. The formation of AOC can be suppressed under appropriate conditions. In this study, chlorination at 4 mg/L, combined with a coagulant dose of 40 mg/L at 20°C over a reaction time of 12 hr, produced the minimum AOC.

关键词： Microcystis aeruginosa Chlorination Assimilable organic carbon（AOC）

Apogossypolone对人前列腺癌LNCaP移植瘤的生长抑制作用(英文)

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The Chinese-German Journal of Clinical Oncology 2012年第1期11卷 33-36页

作者： Yaozhen Chen Haishan Chen Chen Chen Xiaofeng huang Shijie Mu Mengyao Zhang xingbin hu Qunxing An Xianqing Zhang Department of Blood Transfusion Xijing Hospital The Fourth Military Medical University Xi＇an 710032 China Department of Blood Transfusion 210 Hospital of PLA Dalian 116000 China Central laboratory The Fourth Military Medical University Xi＇an 710032 China Department of Chemistry School of Pharmacy The Fourth Military Medical University Xi＇an 710032 China

Objective:The aim of this study was to investigate the inhibitory effect of apogossypolone (ApoG2) on subcutaneous implants of human LNCaP prostatic carcinoma cells, and explore its mechanism. Methods:To establish human LNCaP prostatic carcinoma cell line subcutaneous xenograft models and observe the inhibitory effect of ApoG2 on the tumor model. Immunohistochemistry was employed to observe the expression of Bcl-2, PCNA, CD31, caspase-3 and-8 in tumor tissues. The microvessel density was calculated. Results:ApoG2 could obviously inhibit the growth of subcutaneous prostatic carcinoma implant. ApoG2 decreased the expression of PCNA and CD31, and increased the expression of caspases-3,-8 in tumor tissues. Conclusion:ApoG2 has an inhibitory effect on prostatic carcinoma implants.

关键词：前列腺癌细胞抑制作用植入人类 caspase-3 免疫组织化学方法半胱天冬酶-3 上皮

致敏红细胞BPGM酶活性降低对红细胞携氧/释氧能力的影响研究

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临床输血与检验 2024年第3期26卷 308-314页

作者：孟炜程陈要臻王雅芬安宁刘志新吴晓双王斐胡兴斌空军军医大学第一附属医院输血科陕西西安710032

目的分析致敏红细胞的携氧/释氧能力并初步探讨出现异常的原因。方法用微柱凝胶卡检测致敏红细胞,用携氧/释氧功能评价装置分析自身免疫性溶血性贫血(AIHA)和新生儿溶血病(HDN)患者的致敏红细胞的携氧/释氧能力。使用健康成人的血浆... 详细信息

目的分析致敏红细胞的携氧/释氧能力并初步探讨出现异常的原因。方法用微柱凝胶卡检测致敏红细胞,用携氧/释氧功能评价装置分析自身免疫性溶血性贫血(AIHA)和新生儿溶血病(HDN)患者的致敏红细胞的携氧/释氧能力。使用健康成人的血浆构建输血性溶血反应小鼠模型,对照组给予PBS,记录小鼠负重游泳至力竭的时间,分离小鼠红细胞并分析其携氧/释氧能力,利用蛋白组学对小鼠溶血组与正常组血浆中差异蛋白进行GO和KEGG富集分析。采用ELISA方法检测致敏红细胞BPGM酶活性和2,3-DPG含量。结果与相应对照组相比,AIHA、HDN和输血性溶血反应模型小鼠的红细胞的氧解离曲线均发生左移和P50下降。溶血模型小鼠的负重游泳时间明显缩短,蛋白组学筛选结果发现红细胞BPGM异常,致敏红细胞BPGM酶活性降低且细胞内2,3-DPG含量下降。结论致敏红细胞BPGM酶活性降低导致红细胞释放氧气能力下降。

关键词：红细胞溶血 BPGM 2 3-DPG

Simulation Analysis on Quasistatic Characteristics of Multistage Face Gears with Double Crown Surfac

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Computer Modeling in Engineering & Sciences 2019年第2期118卷 447-470页

作者： xingbin Chen Qingchun hu Zhongyang Xu Yao Ding Qianli Mai Chune Zhu School of Mechanical and Automotive engineering South China University of TechnologyGuangzhou510641China eBizprise Technology(TJ)Limited Tianjin300040China Institute for Biomedical and Pharmaceutical Sciences Guangdong University of TechnologyGuangzhou510006China.

The multistage face gears are the core component of the planetary gear train,which is symmetrically meshed by multiple single-stage face gear and multiple cylindrical gears.However,it is difficult to synchronize the contact between face gears and cylindrical gear due to the tooth number differences.Thus,the interference problems between two stages and big stress concentration are obvious.The crown surface configuration technology and structure design were introduced to optimize the meshing condition.To improve the double crown design feasibility and meshing stability,it is necessary to establish a reasonable multistage face gears pair simulation model to evaluate various influence factors on the contact condition and quasi-static characteristics of multistage face gears structure.The relevant scatter plots are fitted by comparing the contact results with different crown quantities and friction coefficients to intuitively obtain the variation regularity of maximum deformation,maximum strain,maximum stress and maximum strain energy.The natural frequency and mode coefficient are also determined by modal analysis under these two conditions.All the above mentioned studies verified the contact conjugate properties of double crown surface configuration were suitable.The results can provide a foundation for structure optimization and transmission reliability of multistage face gears.

关键词： Multistage face gears quasi-static contact characteristics modal characteristics double crown surface simulation analysis.