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Reducing systemic absorption and macrophages clearance of genistein by lipid-coated nanocrystals for pulmonary delivery

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Chinese Chemical Letters 2023年第1期34卷 245-250页

作者： Yuan He Chang Liu Run Han yingmin liang Judith Choi Wo Mak Yinghao Zhu Haifeng Li Ying Zheng State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacaoChina Department of Pharmacy Xuzhou Medical UniversityXuzhou 221004China LKS Faculty of Medicine Department of MedicineThe University of Hong KongHong KongChina Institute of Applied Physics and Materials Engineering University of MacaoMacaoChina

Pulmonary delivery is an effective drug delivery strategy for the treatment of local respiratory ***,the rapid systemic absorption through the lung due to the thin barrier and persistent lung clearances influence the drug retention in the *** this study,we designed a lipid-coated genistein nanocrystals(Lipo-NCs)formulation to achieve enhanced efficiency of local pulmonary *** LipoNCs were fabricated by modifying genistein nanocrystals(NCs)with phospholipid membrane through thin film hydration following the homogenization *** prepared Lipo-NCs exhibited a decreased drug release rate compared with the naked *** results demonstrated that intracellular uptake and transcellular transport of NCs by the Calu-3 epithelial layer were reduced after lipid ***,the macrophages clearance was also impeded by this Lipo-NCs *** vivo lung retention and distribution revealed that more genistein was retained in the lung after intratracheal administration of *** pharmacokinetic study displayed that the AUC((0-t))values of Lipo-NCs were 1.59-fold lesser than those of the NCs group,indicating a reduced systemic *** conclusion,this research indicated that Lipo-NCs could be a suitable formulation for reducing systemic absorption and macrophages clearance,and thus enhancing drug concentration in lung by pulmonary delivery.

关键词： Pulmonary delivery Lipid-coated nanocrystals Cell uptake Transport Systemic absorption Macrophage clearances

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酪氨酸激酶抑制剂时代异基因造血干细胞移植在慢性髓性白血病治疗中的地位

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中华血液学杂志 2014年第2期35卷 92-93页

作者：粱英民第四军医大学唐都医院血液科西安710038

异基因造血干细胞移植（allo-HSCT）治疗慢性髓性白血病（cML）已有30多年的历史，目前仍然被认为是治愈CML最有效的方法。

关键词：异基因造血干细胞移植慢性髓性白血病酪氨酸激酶抑制剂治疗 CML

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Clinical risk score for invasive fungal diseases in patients with hematological malignancies undergoing chemotherapy:China Assessment of Antifungal Therapy in Hematological Diseases (CAESAR) study

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Frontiers of Medicine 2019年第3期13卷 365-377页

作者： Ling Wang Ying Wang Jiong Hu Yuqian Sun He Huang Jing Chen Jianyong Li Jun Ma Juan Li yingmin liang Jianmin Wang Yan Li Kang Yu Jianda Hu Jie Jin Chun Wang Depei Wu Yang Xiao Xiaojun Huang Blood & Marrow Transplantation Center Department of HematologyCollaborative Innovation Center of HematologyRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200025China Department of Hematology The First Affiliated Hospital of China Medical UniversityShenyang 110001China Department of Hematology The First Affiliated Hospital of Wenzhou Medical CollegeWenzhou 325000China Department of Hematology Fujian Medical University Union HospitalFuzhou 350001China Department of Hematology The First People's Hospital of ShanghaiShanghai 200080China Department of Hematology The First Affiliated Hospital of Soochow UniversitySuzhou 215006China Department of Hematology The General Hospital of Guangzhou Military Command of PLAGuangzhou 510010China Peking University Institute of Hematology Peking UniversityPeople's HospitalBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China Department of Hematology The First Affiliated Hospital of Medical School of Zhejiang UniversityHangzhou 310003China Department of Hematology-Oncology Shanghai Children's Medical CenterShanghai 200127China Department of Hematology Jiangsu Province HospitalNanjing 210029China Harbin Hematologic Tumor Institution Harbin 150010China Department of Hematology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China Department of Hematology Tangdu HospitalFourth Military Medical UniversityXi'an 710032China Department of Hematology Changhai Hospital of the Second Military Medical UniversityShanghai 200082China

Invasive fungal disease (IFD) is a major infectious complication in patients with hematological *** this study,we examined 4889 courses of chemotherapy in patients with hematological diseases to establish a training dataset (n=3500) by simple random sampling to develop a weighted risk score for proven or probable IFD through multivariate regression,which included the following variables: male patients,induction chemotherapy for newly diagnosed or relapsed disease,neutropenia,neutropenia longer than 10 days,hypoalbuminemia,central-venous catheter,and history of *** patients were classified into three groups,which had low (0-10,~1.2%),intermediate (11-15,6.4%),and high risk (> 15,17.5%) of *** the validation set (n=1389),the IFD incidences of the groups were ~1.4%,5.0%,and 21.4%.In addition,we demonstrated that antifungal prophylaxis offered no benefits in low-risk patients,whereas benefits were documented in intermediate (2.1% vs.6.6%,P=0.007) and high-risk patients (8.4% vs.23.3%,P=0.007).To make the risk score applicable for clinical settings,a pre-chemo risk score that deleted all unpredictable factors before chemotherapy was established,and it confirmed that anti-fungal prophylaxis was beneficial in patients with intermediate and high risk of *** conclusion,an objective,weighted risk score for IFD was developed,and it may be useful in guiding antifungal prophylaxis.

关键词： invasive fungal diseases hematological malignancies chemotherapy risk score prophylaxis

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Atomic modulation of Fe‐Co pentlandite coupled with nitrogen‐doped carbon sphere for boosting oxygen catalysis

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Chinese Journal of Catalysis 2022年第6期43卷 1502-1510页

作者： Si‐Jie Li Yong Xie Bi‐Lin Lai yingmin liang Kang Xiao Ting Ouyang Nan Li Zhao‐Qing Liu Institute of Clean Energy and Materials Guangzhou Key Laboratory for Clean Energy and MaterialsMinistry of EducationSchool of Chemistry and Chemical EngineeringGuangzhou UniversityGuangzhou Higher Education Mega CenterGuangzhou 510006GuangdongChina

Reversible oxygen reaction plays a crucial role in rechargeable battery systems,but it is limited by the slow reaction ***,the ionic modulation of cobalt pentlandite coupled with nitrogen‐doped bowl‐like hollow carbon sphere is well designed on octahedral and tetrahedral *** robust FexCo9−xS8‐NHCS‐V with iron replacing at the octahedron possesses prolonged metal sulfur bond and exhibits excellent bifunctional electrocatalytic performance towards oxygen reduction reaction(ORR,E_(1/2)=0.80 V ***)and excellent oxygen evolution reaction(OER,E_(j=10)=1.53 V ***)in 0.1 mol/L ***,a rechargeable Zn‐air battery of Fe_(x)Co_(9−x)S_(8)‐NHCS‐V cathode endows high energy efficiency(102 mW cm^(−2)),and a microbial fuel cell achieves a high‐power density(791±42 mW m^(−2)),outperforming the benchmark Pt/C catalyst.

关键词： Oxygen electrocatalysis Transition metal sulfide Nitrogen‐doped carbon Pentlandite structure Zinc‐air battery

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microRNA与急性移植物抗宿主病研究进展

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中华血液学杂志 2015年第10期36卷 894-896页

作者：胡彬黄斯勇梁英民第四军医大学唐都医院血液科西安710038

急性移植物抗宿主病（aGVHD）是异基因造血干细胞移植（allo-HSCT）后的常见并发症之一，重度aGVHD患者病死率高。HLA全相合患者allo-HSCT aGVHD发生率为40%～60%，HLA不全相合患者发生率更高［1］。aGVHD发病机制复杂，通常认为与免疫... 详细信息

急性移植物抗宿主病（aGVHD）是异基因造血干细胞移植（allo-HSCT）后的常见并发症之一，重度aGVHD患者病死率高。HLA全相合患者allo-HSCT aGVHD发生率为40%～60%，HLA不全相合患者发生率更高［1］。aGVHD发病机制复杂，通常认为与免疫激活、炎症因子释放、细胞数量的改变和影响GVHD中的特定蛋白质水平有关。目前临床上诊断aGVHD主要根据临床特征及病理学证据，仍然缺乏监测、诊断aGVHD的生物标志物。最近，许多文献报道microRNA （miRNA）在aGVHD及肿瘤方面有重要作用。本文我们将miRNA在aGVHD中的研究进展进行综述。

关键词：急性移植物抗宿主病 microRNA allo-HSCT 异基因造血干细胞移植 GVHD发生率 aGVHD miRNA 临床特征

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内皮细胞靶向的可溶性Notch配体hD1R蛋白对急性髓系白血病细胞增殖的影响

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中华血液学杂志 2018年第10期39卷 845-850页

作者：田登梅梁英民张永清解放军第309医院血液科北京100091 空军军医大学唐都医院血液科北京100091

目的探讨内皮细胞靶向的可溶性Notch配体hDlR蛋白对急性髓系白血病（AML）细胞增殖的影响。方法以24例初诊AML患者为研究对象（AML组），以9例白细胞或血小板计数略低，但骨髓象未见异常者为对照（对照组），采用实时定量PCR法检测其骨... 详细信息

目的探讨内皮细胞靶向的可溶性Notch配体hDlR蛋白对急性髓系白血病（AML）细胞增殖的影响。方法以24例初诊AML患者为研究对象（AML组），以9例白细胞或血小板计数略低，但骨髓象未见异常者为对照（对照组），采用实时定量PCR法检测其骨髓CD34＋细胞Notchl、Notch2、Notch3、Notch4、HeslmRNA水平；诱导、表达及纯化内皮细胞靶向的可溶性hDlR融合蛋白。以人脐静脉内皮细胞（HUVEC）作为支持细胞，联合应用重组人干细胞因子（SCF）、TPO、Fit-3配体（FL）、IL-6、IL-3五种人源性生长因子（5GF）及hDlR蛋白为共培养条件，分别将AML组和对照组的CD34＋细胞进行体外培养，分析在hDlR组、PBS组（PBS代替hDlR）、5GF组、γ-分泌酶抑制剂（GSI）组（hD1R＋GSI）4种不同培养条件下CD34。细胞增殖、凋亡情况。并用实时定量PCR法检测培养后的AML组和对照组细胞内Hesl、Bcl-2 mRNA表达。结果①与对照组相比，AML组细胞Notchl、HeslmRNA水平明显下降，Notch4mRNA水平明显升高（P值均〈0．05）。②在不同体外培养条件下，hDlR组、PBS组AML细胞总数分别为（0．74±0．13）×10^5、（2．164±0．21）×10^5，差异有统计学意义（t=5．70，P〈0．01）。③hDIR组培养条件下，AML组、对照组细胞凋亡率分别为（18．48±2．51）％、（3．19±0．58）％，差异有统计学意义（t=5．94，P〈0．01）。AML组不同培养条件下细胞凋亡率比较，hDlR组、5GF组较PBS组明显升高（P值均〈0．05），GSI组较hDlR组明显降低（P〈0．05）。④hD1R蛋白明显上调AML细胞Hesl表达（P〈0．01），下调抗凋亡基因Bcl-2表达（P〈0．05）。结论hDlR蛋白可有效激活AML细胞内Notch信号，下调Bcl-2基因，抑制AML细胞增殖，促进细胞凋亡。

关键词：白血病髓样急性 hDlR蛋白 Notch信号细胞增殖细胞凋亡

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Size Effect of Curcumin Nanocrystals on Airway Mucosa Penetration, Lung Tissue Distribution and Pharmacokinetics Studies by Pulmonary Delivery

Size Effect of Curcumin Nanocrystals on Airway Mucosa Penetr...

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2018年第十二届中国药物制剂大会

作者：何媛 yingmin liang Judith Choi Wo Mak Yonghong Liao Ting Li Ru Yan Haifeng Li Ying Zheng State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical Sciences University of Macau LKS Faculty of Medicine Department of Medicine The University of Hong Kong Institute of Medicinal Plant Development Chinese Academy of Medical Sciences and Peking Union Medical College Institute of Applied Physics and Materials Engineering University of Macau

Objective: Nanocrystal has been introduced for pulmonary delivery of hydrophobic drugs for several years. Although the deposition and bioavailability have been extensively studied, little is known about the absorption process after deposition. The aim of this study is to investigate the size effect of nanocrystals on pulmonary absorption and explore the real time release behavior during this process. Methods: Three different sized curcumin nanocrystals were fabricated by wet milling and anti-solvent precipitation method. The in vitro dissolution, mucus diffusion and Calu-3 uptake and transport studies were investigated. The real time release behavior was studied by the applying of FRET technology. Then the in vivo lung retention and distribution were conducted by drug concentration measurement and fluorescence observing in lung tissue sections after pulmonary administration. The pharmacokinetics study was performed by plasma concentration measurement with LC/MS. Results: The prepared nanocrystals were about 200 nm, 500 nm and 1000 nm with crystal characters. The in vitro dissolution and simulated mucus diffusion studies showed a size depended manner, where the smallest sized nanocrystal exhibited a rapid dissolution velocity and higher diffusion percentage. The Calu-3 cell studies demonstrated that smaller sized nanocrystals displayed higher uptake and transport efficiency. The result of real time dissolution behavior displayed that FRET efficiency decreased continuously from mucus to cells, which demonstrated the nanocrystals dissolved gradually during this process and penetrated through lung epithelium layer mainly by free drug form. The in vivo lung retention determination and histological studies showed that large sized nanocrystals remained higher amount in lung tissue, while small sized absorbed rapidly into blood system. The plasma pharmacokinetics study showed the AUC of small sized nanocrystal was 1.75 and 3.32 times greater than middle and large nanocrysta

关键词： Pulmonary delivery nanocrystals size effect FRET lung absorption

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SV40-LT基因使牙髓干细胞永生化的研究

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实用口腔医学杂志 2022年第2期38卷 189-193页

作者：陈冬雪白喜龙梁英民西安国际医学中心医院西安710100 陕西圆梦生命科学研究院

目的:分离牙髓干细胞,用含有SV40-LT抗原的慢病毒感染牙髓干细胞以建立永生化细胞株并进行鉴定。方法:消化法获得牙髓干细胞;用慢病毒粒子HBLV-SV40LT-3*flag-PURO感染目的细胞,抗生素筛选出稳定传代的细胞株,并进行干性测定。结果:原... 详细信息

目的:分离牙髓干细胞,用含有SV40-LT抗原的慢病毒感染牙髓干细胞以建立永生化细胞株并进行鉴定。方法:消化法获得牙髓干细胞;用慢病毒粒子HBLV-SV40LT-3*flag-PURO感染目的细胞,抗生素筛选出稳定传代的细胞株,并进行干性测定。结果:原代与永生化的牙髓干细胞(iDPSCs)在分化能力及表面标记物的检测无差异;Real-time PCR结果显示,感染组细胞中SV40-LT基因的转录水平显著提高;Western blot结果显示,实验组均可检测到标签蛋白Flag的表达。结论:含有SV40-LT基因片段的慢病毒可使人牙髓干细胞发生永生化,永生化后的细胞仍具有多向分化潜能。

关键词：牙髓干细胞永生化 SV40-LT

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小剂量高三尖杉酯碱＋阿糖胞苷方案诱导治疗不同危险度分层急性髓系白血病效果分析

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白血病．淋巴瘤 2016年第1期25卷 57-60,64页

作者：李丹慧李国辉梁英民第四军医大学唐都医院血液科西安710038

目的探讨小剂量（LD）-高三尖杉酯碱＋阿糖胞苷（HA）方案诱导治疗急性髓系白血病（AML）（除外M3）的临床效果。方法对52例接受LD-HA方案诱导治疗的AML患者资料进行回顾性分析，并依据分子生物学和细胞遗传学危险度分级，观察临床疗效... 详细信息

目的探讨小剂量（LD）-高三尖杉酯碱＋阿糖胞苷（HA）方案诱导治疗急性髓系白血病（AML）（除外M3）的临床效果。方法对52例接受LD-HA方案诱导治疗的AML患者资料进行回顾性分析，并依据分子生物学和细胞遗传学危险度分级，观察临床疗效、不良反应，随访长期生存，以同期49例伊达比星＋阿糖胞苷（IA）方案治疗患者为对照。结果1个疗程后，LD-HA组总有效（OR）率为71．2％（37／52）[完全缓解（CR）率50．0％（26／52），部分缓解（PR）率21．2％（11／52）]，IA组OR率为53．1％（26／49）[CR率44．9％（22／49），PR率8．2％（4／49）]，两组OR率差异无统计学意义（P=0．068）。按危险度分层，LD-HA组高危组的OR率高于IA组[100％（11／11）比66．7％（12／18）]，差异有统计学意义（P〈0．05）；LD—HA组和IA组的低危组和中危组OR率差异无统计学意义（P〉0．05）。LD—HA组心脏毒性及骨髓抑制均较IA组轻，不适合标准方案的AML患者亦对其耐受良好。结论LD-HA方案诱导治疗AML时，高危组OR率高，化疗相关不良反应发生率低，安全性较高。与标准方案相比，LD-HA对于高危AML患者可能更有效。

关键词：小剂量HA方案白血病髓样急性危险度分层分子生物学细胞遗传学

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β-血红蛋白病基因组编辑治疗的研究进展

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遗传 2018年第2期40卷 95-103页

作者：刘佳伟洪涛秦鑫梁英民张萍徐湘民第四军医大学医学遗传学与发育生物学教研室西安710032 湖北文理学院医学院襄阳441053 第四军医大学唐都医院血液科西安710032 不详

β-血红蛋白病(β-hemoglobinopathies)是严重危害人类健康的6种常见疾病之一,尽管其遗传分子机制已被阐释清楚,但目前除异基因骨髓移植外尚还缺乏根治性的治疗策略。近年来,基因组编辑技术的迅速发展及其在人造血干祖细胞中的应用为β... 详细信息

β-血红蛋白病(β-hemoglobinopathies)是严重危害人类健康的6种常见疾病之一,尽管其遗传分子机制已被阐释清楚,但目前除异基因骨髓移植外尚还缺乏根治性的治疗策略。近年来,基因组编辑技术的迅速发展及其在人造血干祖细胞中的应用为β-血红蛋白病的治疗开辟了新的方向。针对血红蛋白的基因突变,可利用同源重组介导的细胞内源性DNA损伤修复途径直接修复遗传缺陷,也可以利用非同源末端连接机制沉默抑制胎儿血红蛋白表达的分子,重新激活胎儿血红蛋白的表达以缓解β-血红蛋白病人的临床症状。本文从β-血红蛋白病的基因组编辑策略及尝试、临床转化平台的要素分析等方面对该病的基因组编辑治疗的研究进展展开综述,以期为β-血红蛋白病新型治愈方案的研究以及基因组编辑技术的临床转化提供参考。

关键词： β-血红蛋白病基因组编辑镰状红细胞贫血 β-地中海贫血 Cas9

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