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Acid-sensitive PEGylated cabazitaxel prodrugs for antitumor therapy

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Chinese Chemical Letters 2021年第5期32卷 1751-1754页

作者： Tao Liu hui Zou Jingqing Mu Na Yu Yang Xu Guohua Liu Xingjie liang Shutao Guo Key Laboratory of Functional Polymer Materials of Ministry of Education State Key Laboratory of Medicinal Chemical Biology and Institute of Polymer ChemistryCollege of ChemistryNankai UniversityTianjin 300071China Laboratory of Controllable Nanopharmaceuticals CAS Center for Excellence in NanoscienceCAS Key Laboratory for Biomedical Effects of Nanomaterials and NanosafetyNational Center for Nanoscience and TechnologyBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China

Although the antitumor drug cabazitaxel shows great therapeutic potential,its high toxicity and poor water solubility limit its ***,the use of stimuli-responsive prodrugs is a promising strategy for overcoming these ***,we report the synthesis of two highly water soluble,acidsensitive PEGylated acyclic-ketal-linked cabazitaxel prodrugs(PKCs)with improved antitumor *** an acidic tumor microenvironment,the PKCs hydrolyzed rapidly to release the native drug,whereas they were stable in the normal physiological *** with cabazitaxel injection,the PKCs had much higher maximum tolerated doses:and in an MDA-MB-231 subcutaneous xenograft nude mouse model,the PKCs showed better antitumor efficacy and safety than cabazitaxel *** prodrug strategy reported herein could be useful for the development of other water soluble,acidsensitive prodrugs with improved efficacy.

关键词： Prodrugs Acid-sensitive Antitumor therapy Cabazitaxel PEGylation

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13个柚木种源/家系生长表现研究

林业科学研究 2024年第1期37卷 1-9页

作者：李运兴梁坤南黄桂华邝炳朝郝建杨保国潘丽琴黄日逸中国林业科学研究院热带林业实验中心广西凭祥532699 中国林业科学研究院热带林业研究所广东广州510520 广西民族师范学院广西崇左532200 广西友谊关森林生态系统国家定位观测研究站崇左凭祥友谊关森林生态系统广西野外科学观测研究站广西凭祥532699

[目的]了解国内柚木种源/家系的遗传变异特征,选育更多适应性强的优良种质。[方法]对采集自海南尖峰岭等地的13个种源/家系进行造林试验,在5、10、37 a时测定树高、胸径,应用方差分析方法进行差异性分析和重复力估算,运用偏相关分析揭... 详细信息

[目的]了解国内柚木种源/家系的遗传变异特征,选育更多适应性强的优良种质。[方法]对采集自海南尖峰岭等地的13个种源/家系进行造林试验,在5、10、37 a时测定树高、胸径,应用方差分析方法进行差异性分析和重复力估算,运用偏相关分析揭示生长因子与地理及气候因子的相关性,进而筛选优良种质。[结果](1)不同种源/家系间37 a生时保存率、树高、胸径、单株材积差异显著,其变化范围分别为68.81%~94.29%、11.72~16.03 m、11.33~17.92 cm、0.0844~0.3291 m^(3)。(2)树高、胸径、材积重复力分别为0.6077、0.5131、0.6344。(3)保存率、树高与地理坐标、气候因子相关不显著;胸径和单株材积与海拔(r=0.938^(**),r=0.868^(**))、年均温(r=0.914^(**),r=0.844^(**))显著正相关,与经度(r=-0.913^(**),r=-0.735^(*))、距离(r=-0.923^(**),r=-0.832^(**))显著负相关。(4)聚类分析结果表明,37 a生时,种源/家系7514的保存率、树高、胸径和单株材积表现最好,8440表现最差,其次是75129。[结论]不同种源/家系间保存率、树高、胸径、单株材积差异显著,树高、单株材积有较高的重复力。柚木引种宜选择年均气温相近且距离较近的种源/家系以获得较好的遗传表现,对于凭祥当地而言,种源/家系7514适宜广泛推广种植。

关键词：柚木种源/家系生长表现相关因子

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邵征洋治疗儿童肥胖症经验

浙江中西医结合杂志 2024年第3期34卷 201-203页

作者：葛亮张春辉刘玥葛泰慧邵征洋浙江中医药大学第二临床医学院杭州310053 杭州市红十字会医院儿科杭州310003

肥胖作为全球突出的健康问题,发病率呈现逐年上升的趋势^([1])。儿童超重肥胖不仅会影响身高,增加儿童期、成年期代谢综合征的风险,还容易产生外貌焦虑等心理障碍,影响患儿正常生活、学习和社交^([1])。WHO倡导要以儿童肥胖防控为全球... 详细信息

肥胖作为全球突出的健康问题,发病率呈现逐年上升的趋势^([1])。儿童超重肥胖不仅会影响身高,增加儿童期、成年期代谢综合征的风险,还容易产生外貌焦虑等心理障碍,影响患儿正常生活、学习和社交^([1])。WHO倡导要以儿童肥胖防控为全球肥胖趋势抑制的着力点,目前临床上儿童肥胖以饮食运动方案为基础,疗效有限且易反复,药物及手术方案在儿童中使用仍然较为谨慎。近年来中医药在小儿肥胖治疗中应用广泛^([2])。邵征洋教授是浙江省名中医,从事儿科临床工作30余载,其运用中医药治疗小儿肥胖特色鲜明。

关键词：儿童肥胖邵征洋临床经验

Expression of insulin-like growth factor binding protein-2 in gastric carcinoma and its relationship with cell proliferation

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World Journal of Gastroenterology 2006年第39期12卷 6285-6289页

作者： liang-hui Shi Xiao-Qun Zhu Guo-Hai Zhao Ya-Bin Xia Yi-Sheng Zhang Department of Surgery Affiliated Yijishan Hospital. Wanna-n Medical College Wuhu 241001 Anhui Province China Departmentof Pathology Wannan Medical College Wuhu 241001 Anhui Province China

AIM: To investigate the expression of insulin-like growth factor binding protein-2 (IGFBP-2) in gastric carcinoma and its clinical significance and to explore its relationship with cell proliferation. METHODS: Expressions of IGFBP-2 and Ki-67 in 118 cases of gastric carcinoma and 40 cases of normal gastric mucosa were detected by EnVision immunohistochemical technique. RESULTS: Expression of IGFBP-2 in gastric carcinoma was higher than that in normal gastric mucosa (P 0.05). Expression of IGFBP-2 in advanced gastric carcinoma was higher than that in early gastric carcinoma (P < 0.05). Expression of IGFBP-2 in gastric carcinoma with lymph node metastasis was higher than that without lymph node metastasis (P < 0.01). IGFBP-2 expression was a positively related to the clinical stage of gastric carcinoma (P < 0.01). There was a positive correlation between IGFBP-2 and Ki-67 (P < 0.05). CONCLUSION: IGFBP-2 may be involved in carcino- genesis and progression of gastric carcinoma by promoting cell proliferation.

关键词： Gastric carcinoma Insulin-like growth factor binding protein Cell proliferation Immunohistochemistry

Analysis of tumor-infiltrating gamma delta T cells in rectal cancer

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World Journal of Gastroenterology 2016年第13期22卷 3573-3580页

作者： liang Rong Ke Li Rui Li hui-Min Liu Rui Sun Xiao-Yan Liu Department of Gastroenterology the Fifth Affiliated Hospital of Xinjiang Medical University Department of Gastroenterology the First Affiliated Hospital of Soochow University

AIM: To investigate the regulatory effect of Vδ1 T cells and the antitumor activity of Vδ2 T cells in rectal ***: Peripheral blood, tumor tissues and para-carcinoma tissues from 20 rectal cancer patients were collected. Naïve CD4 T cells from the peripheral blood of rectal cancer patients were purified by negative selection using a Naive CD4+ T Cell Isolation Kit II (Miltenyi Biotec). Tumor tissues and para-carcinoma tissues were minced into small pieces and digested in a triple enzyme mixture containing collagenase type IV, hyaluronidase, and deoxyribonuclease for 2 h at room temperature. After digestion, the cells were washed twice in RPMI1640 and cultured in RPMI1640 containing 10% human serum supplemented with L-glutamine and 2-mercaptoethanol and 1000 U/mL of IL-2 for the generation of T cells. Vδ1 T cells and Vδ2 T cells from tumor tissues and para-carcinoma tissues were expanded by anti-TCR γδ antibodies. The inhibitory effects of Vδ1 T cells on naïve CD4 T cells were analyzed using the CFSE method. The cytotoxicity of Vδ2 T cells on rectal cancer lines was determined by the LDH ***: The percentage of Vδ1 T cells in rectal tumor tissues from rectal cancer patients was significantly increased, and positively correlated with the T stage. The percentage of Vδ2 T cells in rectal tumor tissues from rectal cancer patients was significantly decreased, and negatively correlated with the T stage. After culture for 14 d with 1 μg/mL anti-TCR γδ antibodies, the percentage of Vδ1 T cells from para-carcinoma tissues was 21.45% ± 4.64%, and the percentage of Vδ2 T cells was 38.64% ± 8.05%. After culture for 14 d, the percentage of Vδ1 T cells from rectal cancer tissues was 67.45% ± 11.75% and the percentage of Vδ2 T cells was 8.94% ± 2.85%. Tumor-infiltrating

关键词： Rectal cancer T cells Vδ 1 T cells Vδ 2 T cells Foxp3 Cytotoxicity

Comparison of TPMT and NUDT15 polymorphisms in Chinese patients with inflammatory bowel disease

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World Journal of Gastroenterology 2018年第8期24卷 941-948页

作者： Hong-hui Wang Ying He Hong-Xian Wang Cheng-Ling Liao Yu Peng Li-jian Tao Wei Zhang hui-Xiang Yang Department of Gastroenterology Xiangya Hospital Central South University Department of Anesthesiology Kunming Angel Women’s & Children’s Hospital Department of Clinical Pharmacology Hunan Key Laboratory of Pharmacogenetics Xiangya Hospital Central South University Department of Nephrology Xiangya Hospital Central South University

AIM To observe gene polymorphisms of TPMT and NUDT15, and compare their predictive value for azathioprine(AZA)-induced leukopenia in inflammatory bowel disease(IBD).METHODS This study enrolled 219 patients diagnosed with IBD in Xiangya Hospital, Central South University, Changsha, China from February 2016 to November 2017. Peripheral blood of all patients was collected to detect their genotypes of TPMT and NUDT15 by pyrosequencing at the Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, Xiangya Hospital. Eighty patients were treated with AZA according to the disease condition. During the first month, patients who received AZA underwent routine blood tests and liver function tests once a week. The endpoint of the study was leukopenia induced by AZA. By analyzing patient characteristics, genotypes and leukopenia induced by drug use, we found the risk factors associated with AZA-induced *** There were 219 patients with IBD(160 men and 59 women), including 39 who were confirmed with ulcerative colitis(UC), 176 with Crohn's disease(CD) and 4 with undetermined IBD(UIBD). There were 44 patients(20.1%) with mutant genotype of NUDT15(C/T); among them, 16 received AZA, and 8(50%) developed leukopenia. There were 175 patients(79.7%) with wild genotype of NUDT15(C/C); among them, 64 received AZA, and 11(17.2%) developed leukopenia. A significant difference was found between NUDT15 C/T and its wild-type C/C(P = 0.004). There were only 3 patients with TPMT mutant genotype of A/G(1.4%) who participated in the research, and 1 of them was treated with AZA and developed leukopenia. The remaining 216 patients(98.6%) were found to bear the wild genotype of TPMT(A/A); among them, 79 patients received AZA, and 18(22.8%) developed leukopenia, and there was no significant difference from those with A/G(P = 0.071). The frequency of TPMT mutation was 1.4%, and NUDT15 mutation rate was significantly higher and reached 20.1%(P = 0.000). Therefore, NU

关键词： NUDT15 TPMT Azathioprine Leukopenia Inflammatory bowel disease Individualized therapy

尿毒清颗粒联合包醛氧淀粉治疗慢性肾衰竭的临床疗效及对氧化应激指标的影响

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医学信息 2024年第18期37卷 104-107页

作者：周燕子王梦琳梁洪富易辉吉水县人民医院肾内科永丰县人民医院新生儿科

目的探究尿毒清颗粒联合包醛氧淀粉治疗慢性肾衰竭（CRF）的临床疗效及对氧化应激指标的影响。方法以2021年4月-2023年5月吉水县人民医院收治的62例CRF患者为研究对象，经随机数字表法分为对照组（31例）和观察组（31例），对照组给... 详细信息

目的探究尿毒清颗粒联合包醛氧淀粉治疗慢性肾衰竭（CRF）的临床疗效及对氧化应激指标的影响。方法以2021年4月-2023年5月吉水县人民医院收治的62例CRF患者为研究对象，经随机数字表法分为对照组（31例）和观察组（31例），对照组给予包醛氧淀粉口服治疗，观察组在其基础上联合尿毒清颗粒治疗，比较两组临床疗效、中医症状积分（恶心呕吐、面浮肢肿、倦怠乏力）、肾功能指标[血肌酐（Cr）、尿素氮（BUN）、尿微量白蛋白（ALB）]、氧化应激指标[C反应蛋白（CRP）、超氧化物歧化酶（SOD）、丙二醛（MDA）]。结果观察组总有效率高于对照组（P<0.05）。两组治疗后恶心呕吐、面浮肢肿、倦怠乏力积分均低于治疗前，且观察组恶心呕吐、面浮肢肿、倦怠乏力积分低于对照组（P<0.05）；两组治疗后Cr、BUN、ALB低于治疗前，且观察组Cr、BUN、ALB低于对照组（P<0.05）；两组治疗后CRP、MDA低于治疗前，SOD高于治疗前，且观察组CRP、MDA低于对照组，SOD高于对照组（P<0.05）。结论尿毒清颗粒联合包醛氧淀粉治疗CRF疗效肯定，可有效缓解患者症状，改善其肾功能，减轻机体氧化应激状态。

关键词：慢性肾衰竭尿毒清颗粒包醛氧淀粉氧化应激肾功能

Coherent Coupling between Microwave and Optical Fields via Cold Atoms

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Chinese Physics Letters 2019年第8期36卷 5-9页

作者： Zhen-Tao liang Qing-Xian Lv Shan-Chao Zhang Wei-Tao Wu Yan-Xiong Du hui Yan Shi-liang Zhu Guangdong Provincial Key Laboratory of Quantum Engineering and Quantum Materials GPETR Center forQuantum Precision Measurement and SPTESouth China Normal UniversityGuangzhou510006 National Laboratory of Solid State Microstructures School of PhysicsNanjing UniversityNanjing210093

We demonstrate a long-coherent-time coupling between microwave and optical fields through cold atomic *** phase information of the microwave field is stored in a coherent superposition state of a cold atomic ensemble and is then read out by two optical fields after 12 ms.A similar operation of mapping the phase of optical fields into a cold atomic ensemble and then retrieving by microwave is also *** studies demonstrate that long-coherent-time cold atomic ensembles could resonantly couple with microwave and optical fields simultaneously,which paves the way for realizing high-efficiency,high-bandwidth,and noiseless atomic q uant um converters.

关键词： Hamiltonian red Microwave

A multiple maneuvering targets tracking algorithm based on a generalized pseudo-Bayesian estimator of first order

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Journal of Zhejiang University-Science C(Computers and Electronics) 2013年第6期14卷 417-424页

作者： Shi-cang ZHANG jian-xun LI liang-bin WU Chang-hai SHI School of Electronic Information and Electrical Engineering Shanghai Jiao Tong University Aviation Key Laboratory of Science and Technology on AISSS AVIC Radar and Avionics Institute

We describe the design of a multiple maneuvering targets tracking algorithm under the framework of Gaussian mixture probability hypothesis density(PHD) ***,a variation of the generalized pseudo-Bayesian estimator of first order(VGPB1) is designed to adapt to the Gaussian mixture PHD filter for jump Markov system models(JMS-PHD).The probability of each kinematic model,which is used in the JMS-PHD filter,is updated with *** weighted sum of state,associated covariance,and weights for Gaussian components are then *** and merging techniques are also adopted in this algorithm to increase *** of the proposed algorithm is compared with that of the JMS-PHD ***-Carlo simulation results demonstrate that the optimal subpattern assignment(OSPA) distances of the proposed algorithm are lower than those of the JMS-PHD filter for maneuvering targets tracking.

关键词： Gaussian mixture PHD filter Jump Markov system Generalized pseudo-Bayesian estimator of first order(GPB1) Multi-target tracking