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Bone infection site targeting nanoparticle-antibiotics delivery vehicle to enhance treatment efficacy of orthopedic implant related infection

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Bioactive Materials 2022年第10期7卷 134-148页

作者： Bin’en Nie Shicheng Huo Xinhua Qu Jingjing Guo Xi liu qimin Hong You Wang Jianping Yang Bing Yue Department of Bone and Joint Surgery Department of OrthopedicsRenji HospitalSchool of MedicineShanghai Jiaotong UniversityShanghai200127China State Key Laboratory for Modification of Chemical Fibers and Polymer Materials College of Materials Science and EngineeringDonghua UniversityShanghai201620China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education)Department of Radiology Peking University Cancer Hospital&InstituteBeijing100142China

Orthopedic implants account for 99%of orthopedic surgeries,however,orthopedic implant-related infection is one of the most serious complications owing to the potential for limb-threatening sequelae and *** antibiotic treatments still lack the capacity to target bone infection sites,thereby resulting in unsatisfactory therapeutic ***,the bone infection site targeting efficacy of D6 and UBI29-41 peptides was investigated,and bone-and-bacteria dual-targeted nanoparticles(NPs)with D6 and UBI29-41 peptides were first fabricated to target bone infection site and control the release of vancomycin in bone infection *** results of this study demonstrated that the bone-and-bacteria dual-targeted mesoporous silica NPs exhibit excellent bone and bacteria targeting efficacy,excellent biocompatibility and effective antibacterial properties in ***,in a rat model of orthopedic implant-related infection with methicillin-resistant Staphylococcus aureus,the growth of bacteria was evidently inhibited without cytotoxicity,thus realizing the early treatment of implant-related ***,the bone-and-bacteria dual-targeted molecule-modified NPs may target bacteria-infected bone sites and act as ideal candidates for the therapy of orthopedic implant-related infections.

关键词： Orthopedic implants Antibiotic treatments Bone infection site targeting Mesoporous silica nanoparticles Antibacterial properties

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FAT1, a direct transcriptional target of E2F1, suppresses cell proliferation, migration and invasion in esophageal squamous cell carcinoma

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Chinese Journal of Cancer Research 2019年第4期31卷 609-619页

作者： Yu Wang Guangchao Wang Yunping Ma Jinglei Teng Yan Wang Yongping Cui Yan Dong Shujuan Shao qimin Zhan Xuefeng liu Institute of Cancer Stem Cell Dalian Medical UniversityDalian 116044China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital&InstituteBeijing 100142China Shenzhen Peking University-The Hong Kong University of Science and Technology(PKU-HKUST)Medical Center Peking University Shenzhen HospitalShenzhen 518036China College of Stomatology Dalian Medical UniversityDalian116044China Key Laboratory of Proteomics Dalian Medical UniversityDalian 116044China

Objective: Growing evidence indicates that FAT atypical cadherin 1(FAT1) has aberrant genetic alterations and exhibits potential tumor suppressive function in esophageal squamous cell carcinoma(ESCC). However, the role of FAT1 in ESCC tumorigenesis remains not well elucidated. The aim of this study was to further investigate genetic alterations and biological functions of FAT1, as well as to explore its transcriptional regulation and downstream targets in ***: The mutations of FAT1 in ESCC were achieved by analyzing a combined study from seven published genomic data, while the copy number variants of FAT1 were obtained from an analysis of our previous data as well as of The Cancer Genome Atlas(TCGA) and Cancer Cell Line Encyclopedia(CCLE) databases using the cBioPortal. The transcriptional regulation of FAT1 expression was investigated by chromatin immunoprecipitation(ChIP) and the luciferase reporter assays. In-cell western, Western blot and reverse transcription-quantitative polymerase chain reaction(RT-qPCR) were used to assess the indicated gene expression. In addition, colony formation and Transwell migration/invasion assays were employed to test cell proliferation, migration and ***, RNA sequencing was used to study the ***: FAT1 was frequently mutated in ESCC and was deleted in multiple cancers. Furthermore, the transcription factor E2 F1 occupied the promoter region of FAT1, and depletion of E2 F1 led to a decrease in transcription activity and mRNA levels of FAT1. Moreover, we found that knockdown of FAT1 promoted KYSE30 and KYSE150 cell proliferation, migration and invasion;while overexpression of FAT1 inhibited KYSE30 and KYSE410 cell proliferation, migration and invasion. In addition, knockdown of FAT1 led to enrichment of the mitogen-activated protein kinase(MAPK) signaling pathway and cell adhesion ***: Our data provided evidence for the tumor suppressive function of FAT1 in ESCC cells and elucid

关键词： E2F1 ESCC FAT1 tumor suppressor

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Defect of SLC38A3 promotes epithelial-mesenchymal transition and predicts poor prognosis in esophageal squamous cell carcinoma

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Chinese Journal of Cancer Research 2020年第5期32卷 547-563页

作者： Rui liu Ruoxi Hong Yan Wang Ying Gong Danna Yeerken Di Yang Jinting Li Jiawen Fan Jie Chen Weimin Zhang qimin Zhan Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital&InstituteBeijing 100142China State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhou 510060China

Objective: Solute carrier family 38(SLC38 s) transporters play important roles in amino acid transportation and signaling transduction. However, their genetic alterations and biological roles in tumors are still largely *** study aimed to elucidate the genetic signatures of SLC38 s transporters and their implications in esophageal squamous cell carcinoma(ESCC).Methods: Analyses on somatic mutation and copy number alterations(CNAs) of SLC38 A3 were performed as described. Immunohistochemistry(IHC) assay and Western blot assay were used to detect the protein expression level. MTS assay, colony formation assay, transwell assay and wound healing assay were used to explore the malignant phenotypes of ESCC cells. Immunofluorescence assay was used to verify the colocalization of two indicated proteins and immunopreciptation assay was performed to confirm the interaction of ***: Our findings revealed that SLC38 s family was significantly disrupted in ESCC, with high frequent CNAs and few somatic mutations. SLC38 A3 was the most frequent loss gene among them and was linked to poor survival and lymph node metastasis. The expression of SLC38 A3 was lower in tumor tissues compared to that in normal tissues, which was also significantly associated with worse clinical outcome. Further experiments revealed that depletion of SLC38 A3 could promote EMT in ESCC cell lines, and the interaction of SLC38 A3 and SETDB1 might lead to the reduced transcription of Snail. Pharmacogenomic analyses demonstrated that fifteen inhibitors were showed significantly correlated with SLC38 A3 ***: Our investigations have provided insights that SLC38 A3 could act as a suppressor in EMT pathway and serve as a prognostic factor and predictor of differential drug sensitivities in ESCC.

关键词： Amino acid transporter esophageal squamous cell carcinoma epithelial-mesenchymal transition genomic alterations SLC38A3 SETDB1 Snail

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CDK7-YAP-LDHD axis promotes D-lactate elimination and ferroptosis defense to support cancer stem cell-like properties

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Signal Transduction and Targeted Therapy 2023年第9期8卷 4346-4364页

作者： Mengzhu Lv Ying Gong Xuesong liu Yan Wang Qingnan Wu Jie Chen Qingjie Min Dongyu Zhao Xianfeng Li Dongshao Chen Di Yang Danna Yeerken Rui liu Jinting Li Weimin Zhang qimin Zhan Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of Molecular OncologyPeking University Cancer Hospital and InstituteBeijing 100142China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of Breast OncologyPeking University Cancer Hospital and InstituteBeijing 100142China Research Unit of Molecular Cancer Research Chinese Academy of Medical SciencesBeijing 100021China Peking University International Cancer Institute Beijing 100191China Institute of Cancer Research Shenzhen Bay LaboratoryShenzhen 518107China Department of Oncology Cancer InstitutePeking University Shenzhen HospitalShenzhen Peking University-Hong Kong University of Science and Technology(PKU-HKUST)Medical CenterShenzhen 518036China Soochow University Cancer Institute Suzhou 215127China

Reprogrammed cellular metabolism is essential for maintaining cancer stem cells(CSCs)***,we report that mitochondrial D-lactate catabolism is a necessary initiating oncogenic event during tumorigenesis of esophageal squamous cell carcinoma(ESCC).We discover that cyclin-dependent kinase 7(CDK7)phosphorylates nuclear Yes-associated protein 1(YAP)at S127 and S397 sites and enhances its transcription function,which promotes D-lactate dehydrogenase(LDHD)protein ***,LDHD is enriched significantly in ESCC-CSCs rather than differentiated tumor cells and high LDHD status is connected with poor prognosis in ESCC ***,the CDK7-YAP-LDHD axis helps ESCC-CSCs escape from ferroptosis induced by D-lactate and generates pyruvate to satisfy energetic demands for their elevated self-renewal ***,we conclude that esophageal CSCs adopt a D-lactate elimination and pyruvate accumulation mode dependent on CDK7-YAP-LDHD axis,which drives stemness-associated hallmarks of ***,targeting metabolic checkpoints may serve as an effective strategy for ESCC therapy.

关键词： esophageal metabolism elevated

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危重烧伤老年患者早期临床特征的多中心回顾分析及预后的危险因素分析

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中华烧伤与创面修复杂志 2024年第3期40卷 249-257页

作者：马琪敏汤文彬李孝建常菲尹希陈昭宏吴国华夏成德李晓亮王德运储志刚张逸王磊吴抽浪童亚林崔培郭光华朱志豪黄圣宇常刘刘锐刘永计王玉松刘晓彬沈拓朱峰海军军医大学第一附属医院烧伤外科上海200433 同济大学附属东方医院重症医学科上海200120 暨南大学附属广州市红十字会医院烧伤整形科广州510220 张家港市第一人民医院烧伤整形科张家港215600 福建医科大学附属协和医院烧伤科福州350001 郑州市第一人民医院烧伤科郑州450004 武汉大学同仁医院暨武汉市第三医院烧伤科武汉430060 南通大学附属医院烧伤整形科南通226001 浙江省台州医院烧伤科临海317000 解放军第924医院烧伤整形科桂林541002 南昌大学第一附属医院烧伤整形与创面修复医学中心南昌330006 大连市第四人民医院烧伤整形科大连116031 黑龙江省医院烧伤科哈尔滨150036

目的探讨危重烧伤老年患者早期临床特征及预后的危险因素。方法该研究为回顾性病例系列研究。收集2015年1月—2020年12月12家医院收治的符合入选标准的124例危重烧伤老年患者的临床资料,其中大连市第四人民医院4例、福建医科大学附属协... 详细信息

目的探讨危重烧伤老年患者早期临床特征及预后的危险因素。方法该研究为回顾性病例系列研究。收集2015年1月—2020年12月12家医院收治的符合入选标准的124例危重烧伤老年患者的临床资料,其中大连市第四人民医院4例、福建医科大学附属协和医院5例、暨南大学附属广州市红十字会医院22例、黑龙江省医院5例、海军军医大学第一附属医院27例、南昌大学第一附属医院9例、南通大学附属医院10例、武汉大学同仁医院暨武汉市第三医院9例、解放军第924医院12例、张家港市第一人民医院6例、浙江省台州医院4例、郑州市第一人民医院11例。统计患者的总体临床特征,包括性别、年龄、体重指数、烧伤总面积、Ⅲ度烧伤面积、吸入性损伤情况、致伤因素、是否合并基础疾病以及伤后入院时间。根据伤后28 d内的存活结局,将患者分为存活组(89例)与死亡组(35例),比较2组患者基本资料与伤情(同前总体临床特征);伤后第1个24 h凝血指标,包括凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间、D-二聚体、纤维蛋白降解产物(FDP)、国际标准化比值(INR)、纤维蛋白原;伤后第1个24 h血常规指标,包括白细胞计数、血小板计数、中性粒细胞与淋巴细胞比值、单核细胞计数、红细胞计数、血红蛋白、血细胞比容;伤后第1个24 h脏器功能指标,包括直接胆红素、总胆红素、尿素、血肌酐、天冬氨酸转氨酶、丙氨酸转氨酶、总蛋白、白蛋白、球蛋白、血糖、甘油三酯、总胆固醇、碱性磷酸酶、肌酸激酶、电解质指标(血钾、血钠、血氯、血钙、血镁及血磷)、尿酸、肌红蛋白、脑钠肽;伤后第1个24 h感染及血气指标,包括降钙素原、C反应蛋白、pH值、氧合指数、碱剩余、乳酸;治疗情况,包括是否行机械通气、是否行连续性肾脏替代治疗、是否行抗凝治疗、是否应用血管活性药及液体复苏情况。筛选影响危重烧伤老年患者伤后28 d死亡的独立危险因素。结果124例患者中男82例、女42例,年龄60~97岁,体重指数23.44(21.09,25.95)kg/m^(2),烧伤总面积54.00%(42.00%,75.00%)体表总面积(TBSA),Ⅲ度烧伤面积25.00%(10.00%,40.00%)TBSA,主要为中重度吸入性损伤,以火焰烧伤者为主,合并基础疾病者43例,以伤后入院时间≤8 h者为主。2组患者年龄,烧伤总面积,Ⅲ度烧伤面积,吸入性损伤情况,伤后第1个24 h PT、APTT、D-二聚体、FDP、INR、白细胞计数、血小板计数、尿素、血肌酐、血糖、血钠、尿酸、肌红蛋白、尿量比较,差异均有统计学意义(Z值分别为2.37、5.49、5.26、5.97、2.18、1.95、2.68、2.68、2.51、2.82、2.14、3.40、5.31、3.41、2.35、3.81、2.16、-3.82,P<0.05);是否行机械通气、是否应用血管活性药比较,差异均有统计学意义(χ^(2)值分别为9.44、28.50,P<0.05)。年龄、烧伤总面积、Ⅲ度烧伤面积、伤后第1个24 h血肌酐、伤后第1个24 h APTT均为危重烧伤老年患者伤后28 d死亡的独立危险因素(比值比分别为1.17、1.10、1.10、1.09、1.27,95%置信区间分别为1.03~1.40、1.04~1.21、1.05~1.19、1.05~1.17、1.07~1.69,P<0.05)。结论危重烧伤老年患者多为火焰烧伤,常伴随中重度吸入性损伤,早期常伴有炎症反应增强、血糖升高、纤溶激活、脏器功能损害等,这与其预后相关。年龄、烧伤总面积、Ⅲ度烧伤面积、伤后第1个24 h血肌酐和APTT是该群体伤后28 d死亡的独立危险因素。

关键词：烧伤老年人预后危险因素回顾性研究

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Enhanced Expression of miR-425 Promotes Esophageal Squamous Cell Carcinoma Tumorigenesis by Targeting SMAD2

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Journal of Genetics and Genomics 2015年第11期42卷 601-611页

作者： Lingyan liu Zitong Zhao Wei Zhou Xinyi Fan qimin Zhan Yongmei Song State Key Laboratory of Molecular Oncology Cancer Institute and HospitalChinese Academy of Medical Sciences and Peking Union Medical College

Esophageal squamous cell carcinoma （ESCC） is one of the most common and deadly cancers in the world, Currently, clinical therapy of ESCC remains limited and the five-year survival rate is poor. The function of miR-425 has been reported in multiple human cancers. However. the tumorigenic role and clinical significance of miR-425 in ESCC remains unclear. We found that enhanced expression of miR- 425 in ESCC cell lines not only promoted cell proliferation and colony formation, but also increased cellular metastasis. Furthermore, we revealed the mechanism that miR-425 inhibited the expression of SMAD2 by targeting the second binding site in the 3＇-untranslated region （3＇-UTR） in ESCC. This mode of action influenced not only SMAD2 rnRNA expression but also protein expression. In addition, we detected the expression of miR-425 in ESCC tissues and plasma. Moreover, we analyzed the relationship between miR-425 expression and SMAD2 mRNA expression. We found that miR-425 was overexpressed in ESCC tissues and the plasma relative to adjacent normal tissues and plasma of healthy individuals. Furthermore, there was a negative correlation between miR-425 expression and SMAD2, Taken together, our results show that miR-425 functions as an oncogene by targeting the 3＇-UTR of SMAD2 and indicate the potential utility of plasma miR-425 as a novel biomarker for ESCC diagnosis.

关键词： Esophageal squamous cell carcinoma miR-425 Plasma miRNA SMAD2

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Crystal structure of human Gadd45 reveals an active dimer

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Protein & Cell 2011年第10期2卷 814-826页

作者： Wenzheng Zhang Sheng Fu Xuefeng liu Xuelian Zhao Wenchi Zhang Wei Peng Congying Wu Yuanyuan Li Xuemei Li Mark Bartlam Zong-Hao Zeng qimin Zhan Zihe Rao National Laboratory of Biomacromolecules Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Tianjin Key Laboratory of Protein Science College of Life SciencesNankai UniversityTianjin 300071China Laboratory of Structural Biology Tsinghua UniversityBeijing 100084China State Key Laboratory of Molecular Oncology Cancer InstituteChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

The human Gadd45 protein family plays critical roles in DNA repair,negative growth control,genomic stability,cell cycle checkpoints and *** we report the crystal structure of human Gadd45,revealing a unique dimer formed via a bundle of four parallel helices,involving the most conserved residues among the Gadd45 *** analysis of human Gadd45 identified a conserved,highly acidic patch in the central region of the dimer for interaction with the proliferating cell nuclear antigen(PCNA),p21 and cdc2,suggesting that the parallel dimer is the active form for the *** assays indicate that:(1)dimerization of Gadd45 is necessary for apoptosis as well as growth inhibition,and that cell growth inhibition is caused by both cell cycle arrest and apoptosis;(2)a conserved and highly acidic patch on the dimer surface,including the important residues Glu87 and Asp89,is a putative interface for binding proteins related to the cell cycle,DNA repair and *** results reveal the mechanism of self-association by Gadd45 proteins and the importance of this self-association for their biological function.

关键词： crystal structure Gadd45 dimer DNA repair growth inhibition apoptosis

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Long non-coding RNA colon cancer-associated transcript 1-Vimentin axis promoting the migration and invasion of HeLa cells

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中华医学杂志（英文版） 2023年第19期136卷 2351-2361页

作者： Zhangfu Li Jiangbei Yuan Qingen Da Zilong Yan Jianhua Qu Dan Li Xu liu qimin Zhan Jikui liu China 518036 China Department of Cardiovascular Surgery Peking University Shenzhen Hospital Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center Shenzhen Guangdong 518036 China518036 China 518036 China 100021 China Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Laboratory of Molecular Oncology Peking University Cancer Hospital & Institute Beijing 100142 China100021

Background: Long non-coding RNA colon cancer-associated transcript 1 (CCAT1) is involved in transforming multiple cancers into malignant cancer types. Previous studies underlining the mechanisms of the functions of CCAT1 primarily focused on its decoy for miRNAs (micro RNAs). However, the regulatory mechanism of CCAT1–protein interaction associated with tumor metastasis is still largely unknown. The present study aimed to identify proteome-wide CCAT1 partners and explored the CCAT1–protein interaction mediated tumor metastasis. Methods: CCAT1–proteins complexes were purified and identified using RNA antisense purification coupled with the mass spectrometry (RAP-MS) method. The database for annotation, visualization, and integrated discovery and database for eukaryotic RNA binding proteins (EuRBPDB) websites were used to bioinformatic analyzing CCAT1 binding proteins. RNA pull-down and RNA immunoprecipitation were used to validate CCAT1–Vimentin interaction. Transwell assay was used to evaluate the migration and invasion abilities of HeLa cells. Results: RAP-MS method worked well by culturing cells with nucleoside analog 4-thiouridine, and cross-linking was performed using 365 nm wavelength ultraviolet. There were 631 proteins identified, out of which about 60% were RNA binding proteins recorded by the EuRBPDB database. Vimentin was one of the CCAT1 binding proteins and participated in the tumor metastasis pathway. Knocked down vimetin ( VIM ) and rescued the downregulation by overexpressing CCAT1 demonstrated that CCAT1 could enhance tumor migration and invasion abilities by stabilizing Vimentin protein. Conclusion: CCAT1 may bind with and stabilize Vimentin protein, thus enhancing cancer cell migration and invasion abilities.

关键词： lncRNA CCAT1 RAP-MS RNA binding protein Vimentin Migration Invasion

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New ranking methods of intuitionistic fuzzy numbers and Pythagorean fuzzy numbers

New ranking methods of intuitionistic fuzzy numbers and Pyth...

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第32届中国控制与决策会议

作者： Zhang Qiang Hu JunHua liu An Chen GuoMing Yan qimin Aeronautics Engineering College Air Force Engineering University

The ranking method can distinguish the size of intuitionistic fuzzy numbers and Pythagorean fuzzy numbers,and plays an important role in the application of intuitionistic fuzzy sets and Pythagorean fuzzy *** on the summary of classic ranking methods,this paper proposes some new ranking ***,some basic concepts of intuitionistic fuzzy set and Pythagorean fuzzy set are ***,four existing ranking methods of intuitionistic fuzzy numbers and four existing ranking methods of Pythagorean fuzzy numbers are ***,the new ranking methods of intuitionistic fuzzy numbers and Pythagorean fuzzy numbers are proposed ***,the accuracy and reliability of the new ranking methods are verified by case analysis.

关键词： intuitionistic fuzzy set intuitionistic fuzzy number Pythagorean fuzzy set Pythagorean fuzzy number ranking method

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一种基于萘酰亚胺并噁嗪的CN-探针

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山东化工 2024年第3期53卷 23-26页

作者：柳锦琦夏仁汝袁丽媛陆靖一陈骑敏任家强王薇湖北工业大学材料与化学工程学院湖北武汉430068 湖北大学生命科学学院湖北武汉430062

虽然氰离子的检测分析方法有多种,但仍存在着一些不足的地方,如响应时间较长、灵敏度不高,离子选择性也有待改善,或者在检测前须采取其他方法先处理干扰离子等。合成了一类含有萘酰亚胺基团的噁嗪光致变色化合物,表现出良好的光致变色性... 详细信息

虽然氰离子的检测分析方法有多种,但仍存在着一些不足的地方,如响应时间较长、灵敏度不高,离子选择性也有待改善,或者在检测前须采取其他方法先处理干扰离子等。合成了一类含有萘酰亚胺基团的噁嗪光致变色化合物,表现出良好的光致变色性能,同时也对氰离子具有很好的识别性能、高选择性、良好的抗干扰能力、很低的检测极限和快速的响应时间,对于氰离子的在线检测也有着潜在的应用价值。

关键词：氰离子噁嗪萘酰亚胺

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