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Distinct transcriptomic landscapes of cutaneous basal cell carcinomas and squamous cell carcinomas

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Genes & Diseases 2021年第2期8卷 181-192页

作者： Jun Wan Hongji Dai Xiaoli Zhang Sheng Liu Yuan Lin Ally-Khan Somani Jingwu Xie jiali han Department of Medical and Molecular Genetics Indiana University School of MedicineIndianapolisIN46202USA Center for Computational Biology and Bioinformatics Indiana University School of MedicineIndianapolisIN46202USA School of Informatics and Computing Indiana University e Purdue University at IndianapolisIndianapolisIN46202USA Department of Epidemiology and Biostatistics Key Laboratory of Cancer Prevention and TherapyNational Clinical Research Center of CancerTianjin Medical University Cancer Institute and HospitalTianjin300000PR China Wells Center for Pediatric Research Department of PediatricsIndiana University School of MedicineIndianapolisIN46202USA Melvin and Bren Simon Cancer Center Indiana University School of MedicineIndianapolisIN46202USA Department of Epidemiology Richard M.Fairbanks School of Public HealthIndiana UniversityIndianapolisIN46202USA Dermatologic Surgery&Cutaneous Oncology Division Department of DermatologyIndiana University School of MedicineIndianapolisIN46202USA

The majority of non-melanoma skin cancer(NMSC)is cutaneous basal cell carcinoma(BCC)or squamous cell carcinoma(SCC),which are also called keratinocyte carcinomas,as both of them originate from *** incidence of keratinocyte carcinomas is over 5 million per year in the US,three-fold higher than the total incidence of all other types of cancer *** there are several reports on gene expression profiling of BCC and SCC,there are significant variations in the reported gene expression changes in different *** reason is that tumor-adjacent normal skin specimens were not included in many studies as matched ***,while numerous studies of skin stem cells in mouse models have been reported,their relevance to human skin cancer remains *** this report,we analyzed gene expression profiles of paired specimens of keratinocyte carcinomas with their matched normal skin tissues as the *** several novel findings,we discovered a significant number of zinc finger encoding genes up-regulated in human *** BCC,a novel link was found between hedgehog signaling,Wnt signaling,and the *** the SCC cancerstem-cell gene signature is shared between human and mouse SCCs,the hair follicle stem-cell signature of mice was not highly represented in human *** gene expression(DEG)in human BCC shares gene signature with both bulge and epidermal stem *** have also determined that human BCCs and SCCs have distinct gene expression patterns,and some of them are not fully reflected in current mouse models.

关键词： Basal cell carcinoma Gli1 Hedgehog signaling PTCH1 Squamous cell carcinoma

Repurposing disulfiram with CuET nanocrystals:Enhancing anti-pyroptotic effect through NLRP3 inflammasome inhibition for treating inflammatory bowel diseases

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2698-2715页

作者： Xueming Xu Yuanfeng han jiali Deng Shengfeng Wang Shijie Zhuo Kai Zhao Wenhu Zhou Hematology and Department of Critical Care Medicine The Third Xiangya HospitalCentral South UniversityChangsha 410013China Xiangya School of Pharmaceutical Sciences Central South UniversityChangsha 410013China Hunan Chidren's Hospital Changsha 410007China Department of Pharmacy The Third Xiangya HospitalCentral South UniversityChangsha 410013China Key Laboratory of Biological Nanotechnology of National Health Commission Changsha 410008China

Drug repurposing offers a valuable strategy for identifying new therapeutic applications for existing ***,disulfiram(DSF),a drug primarily used for alcohol addiction treatment,has emerged as a potential treatment for inflammatory diseases by inhibiting pyroptosis,a form of programmed cell *** therapeutic activity of DSF can be further enhanced by the presence of Cu^(2+),although the underlying mechanism of this enhancement remains *** this study,we investigated the mechanistic basis of Cu^(2+)-induced enhancement and discovered that it is attributed to the formation of a novel copper ethylthiocarbamate(CuET)*** exhibited significantly stronger anti-pyroptotic activity compared to DSF and employed a distinct mechanism of ***,despite its potent activity,CuET suffered from poor solubility and limited permeability,as revealed by our druggability *** overcome these intrinsic limitations,we developed a scalable method to prepare CuET nanocrystals(CuET NCs)using a metal coordination-driven self-assembly *** studies demonstrated that CuET NCs exhibited a 6-fold improvement in ***,CuET NCs exhibited high biodistribution in the intestine,suggesting their potential application for the treatment of inflammatory bowel diseases(IBDs).To evaluate their therapeutic efficacy in vivo,we employed a murine model of DSS-induced colitis and observed that CuET NCs effectively attenuated inflammation and ameliorated colitis *** findings highlight the discovery of CuET as a potent anti-pyroptotic agent,and the development of CuET NCs represents a novel approach to enhance the druggability of CuET.

关键词： Drug repurposing Pyroptosis Nanoparticles Bioavailability Disulfiram DSS-induced colitis NLRP3 inflammasome CuET

环状RNA circAZIN1在骨关节炎中调控软骨细胞退变的作用机制

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重庆医学 2024年第10期53卷 1446-1453页

作者：王湘江韩嘉跞杨浪温国洪关鸿王贵清利洪艺广州医科大学附属清远医院/清远市人民医院骨科五区广东清远511518

目的研究环状RNA(circRNA)hsa_circ_0003304(circAZIN1)在骨关节炎(OA)中调控软骨细胞退变的作用及机制。方法基因芯片检测人脂肪源性干细胞(hADSC)成软骨分化过程中circRNA的表达水平变化。从基因芯片检测差异化表达最明显的前10位circ... 详细信息

目的研究环状RNA(circRNA)hsa_circ_0003304(circAZIN1)在骨关节炎(OA)中调控软骨细胞退变的作用及机制。方法基因芯片检测人脂肪源性干细胞(hADSC)成软骨分化过程中circRNA的表达水平变化。从基因芯片检测差异化表达最明显的前10位circRNA中,用IL-β及TNF-α构建的软骨细胞炎症模型进一步筛选出circAZIN1,过表达circAZIN1(转染pcDNA3.1-circAZIN1-EF1-ZsGreen质粒)后实时荧光定量PCR(qPCR)检测其对软骨细胞外基质(ECM)代谢的影响。RNA-蛋白体外结合(RNA pull down)试验检测circAZIN1结合的蛋白,miRNA-circRNA Interactions预测circAZIN1可能海绵吸附的微RNA(miRNA)及其位点,进一步利用TargetMiner、miRDB及TargetScan数据库预测circAZIN1可能海绵吸附的miRNA及下游mRNA,过表达miRNA后检测circAZIN1、miRNA及下游的mRNA是否存在镜像调控现象。结果circAZIN1在hADSC成软骨分化过程中(第3天和第21天)、IL-β及TNF-α构建的软骨细胞炎症模型中差异化表达最明显(第3天组vs.第21天组、对照组***-β组、对照组***-α组);过表达circAZIN1可促进软骨细胞ECM的合成、抑制其分解;RNA-Pull down试验检测到circAZIN1明显结合AGO2蛋白,提示circAZIN1海绵吸附miRNAs的可能性大,进一步数据库预测circAZIN1的下游miRNA为hsa-miR-654-3p,而hsa-miR-654-3p的下游mRNA为CACNA1I,最后过表达hsa-miR-654-3p后qPCR检测证实circAZIN1、hsa-miR-654-3p及CACNA1I间存在镜像调控现象。结论circAZIN1通过海绵吸附hsa-miR-654-3p继而抑制CACNA1I的沉默效应从而发挥抑制软骨细胞退变的作用,这为circRNA在OA发生、发展中的调控机制研究提供了参考。

关键词：骨关节炎软骨退变软骨细胞环状RNA 海绵吸附

深度贫困地区农村劳动力流动减贫的理论逻辑与实践路径

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云南民族大学学报（哲学社会科学版） 2020年第4期37卷 92-102页

作者：韩佳丽西南政法大学经济学院重庆401120

在深度贫困地区扶贫政策的边际成本不断上升、边际效益不断下降的背景下,农村劳动力流动是助推深度贫困地区脱贫攻坚目标实现的重要途径。理论逻辑分析表明深度贫困地区农村劳动力流动减贫效应的传导路径主要包括:促进收入增长,缓解物... 详细信息

在深度贫困地区扶贫政策的边际成本不断上升、边际效益不断下降的背景下,农村劳动力流动是助推深度贫困地区脱贫攻坚目标实现的重要途径。理论逻辑分析表明深度贫困地区农村劳动力流动减贫效应的传导路径主要包括:促进收入增长,缓解物质贫困;培育人力资本,缓解能力贫困;强化社会参与,缓解权利贫困。决胜脱贫攻坚阶段,深度贫困地区需夯实农村劳动力个体的能力基础、实现农村家庭劳动力要素的合理配置、提升深度贫困地区产业的发展程度,保障农村劳动力流动减贫效应的有效发挥。

关键词：深度贫困地区农村劳动力流动贫困减缓理论逻辑实践路径

Can Tibetan medicine Honghua Ruyi pills relieve endometriosisassociated dysmenorrhea?Protocol for a randomized placebocontrolled trial

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Journal of Traditional Chinese Medical Sciences 2024年第1期11卷 78-85页

作者： Mei han Jiahui Cao jiali Wei Hui Luo Chaoqin Yu Xuefang Liang Nyangmotse Guoyan Yang Huilan Du Jianping Liu Centre for Evidence-Based Chinese Medicine Beijing University of Chinese MedicineBeijing 102488China College of Management Beijing University of Chinese MedicineBeijing 102488China College of Acupuncture and Moxibustion Beijing University of Chinese MedicineBeijing 102488China Institute for Tibetan Medicine China Tibetology Research CenterBeijing 100101China Changhai Hospital Naval Medical UniversityShanghai 200433China Department of Gynaecology Guangdong Provincial Hospital of Chinese MedicineGuangdong 510120China Department of Gynaecology Tibetan Medicine Hospital of Qinghai ProvinceXining 810007China NICM Health Research Institute Western Sydney UniversityPenrithNSW 2751Australia College of Integrated Chinese and Western Medicine Hebei University of Chinese MedicineShijiazhuang 050200China

Objective:To provide high-quality clinical evidence of the efficacy of Tibetan medicine Honghua Ruyi(HHRY)pills for endometriosis-associated ***:This study constitutes a multicenter,randomized,double-blind,placebo-controlled trial encompassing a three-menstrual cycle intervention followed by a three-menstrual cycle follow-up period.A total of 164 eligible females with endometriosis-associated dysmenorrhea were randomly divided into HHRY pills and placebo groups in a 1:1 *** primary outcome included dysmenorrhea symptoms assessed using Visual Analog Scale(VAS)scores and quality of life,whereas the secondary outcome measures included the maximum VAS for non-menstrual pelvic pain,duration of pain episodes(in days),frequency and quantity of the consumption of ibuprofen sustained-release capsules(or other non-steroidal anti-inflammatory drugs),and days off work/study for staff/student due to dysmenorrhea,ovarian cyst,and/or pelvic nodule *** safety was monitored throughout the treatment *** the analyses were based on the intention-to-treat *** continuous outcomes,simple or multiple linear regressions were used to estimate the differences between the HHRY pills and placebo groups,with categorical data expressed as the number and percentage of *** were compared using the chi-square test or Fisher's exact *** predefined analysis was adjusted for concomitant treatment,a variable considered to be associated with outcomes but unaffected by treatment *** of treatment effects were reported with 95%confidence ***-tailed P values≤.05 were considered statistically ***:Positive results from this trial,upon completion would provide robust evidence for the efficacy and safety of HHRY pills in treating dysmenorrhea in patients with endometriosis.

关键词： Endometriosis Dysmenorrhea Honghua Ruyi pills Randomized controlled trial Traditional Chinese medicine

法舒地尔对变应性鼻炎小鼠鼻黏膜中Th1/Th2、Th17/Treg相关细胞因子的影响

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中国医科大学学报 2020年第7期49卷 593-596页

作者：张玉韩佳利中国医科大学附属第一医院耳鼻咽喉科沈阳110001

目的探讨Rho激酶抑制剂法舒地尔对变应性鼻炎小鼠鼻黏膜中辅助性T细胞1 (Th1)、辅助性T细胞2 (Th2)、辅助性T细胞17 (Th17)的相关细胞因子(IFN-γ、IL-4、IL-17)及调节性T细胞(Treg)的特异性转录因子Foxp3 mRNA表达水平的影响。方法将C5... 详细信息

目的探讨Rho激酶抑制剂法舒地尔对变应性鼻炎小鼠鼻黏膜中辅助性T细胞1 (Th1)、辅助性T细胞2 (Th2)、辅助性T细胞17 (Th17)的相关细胞因子(IFN-γ、IL-4、IL-17)及调节性T细胞(Treg)的特异性转录因子Foxp3 mRNA表达水平的影响。方法将C57小鼠随机分为AR组(变应性鼻炎小鼠未给予药物治疗,n=8)、法舒地尔组(变应性鼻炎小鼠给予法舒地尔治疗,n=8)、对照组(正常小鼠未给予药物治疗,n=8)。利用卵清蛋白(OVA)建立小鼠变应性鼻炎模型。小鼠鼻黏膜HE染色,比较3组小鼠呼吸区黏膜的形态结构。实时荧光定量PCR法检测每组小鼠鼻黏膜中IFN-γmRNA、IL-4 mRNA、IL-17 mRNA及Treg的特异性核转录因子Foxp3 mRNA的表达水平。结果与对照组比较,AR组IL-4 mRNA、IL-17 mRNA表达明显升高,IFN-γmRNA、Foxp3mRNA表达降低(均P <0.05)。与AR组比较,法舒地尔组变应性鼻炎症状(喷嚏、流涕、抓搔鼻部)明显缓解,嗜酸性粒细胞浸润减少,黏膜水肿减轻。IL-4 mRNA表达明显降低,IFN-γmRNA、Foxp3 mRNA、IL-17 mRNA表达明显升高(均P <0.05)。结论法舒地尔可抑制变应性鼻炎小鼠鼻黏膜炎症反应,改善鼻黏膜局部Th1/Th2、Th17/Treg的免疫失衡。

关键词：变应性鼻炎法舒地尔辅助性T细胞1 辅助性T细胞2 辅助性T细胞17 调节性T细胞细胞因子

基于Agent的情感劝说的决策过程及模型研究

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管理工程学报 2020年第2期34卷 231-238页

作者：伍京华韩佳丽王佳莹中国矿业大学(北京)管理学院北京100083

Agent具有情感后进行的劝说决策会更加理性,而现有研究还不够全面深入。针对此问题,首先结合形式逻辑理论,定义了基于Agent的情感劝说及其决策过程,并将基于Agent的情感劝说的决策过程划分为评价情感劝说行为、更新情感劝说状态、调整... 详细信息

Agent具有情感后进行的劝说决策会更加理性,而现有研究还不够全面深入。针对此问题,首先结合形式逻辑理论,定义了基于Agent的情感劝说及其决策过程,并将基于Agent的情感劝说的决策过程划分为评价情感劝说行为、更新情感劝说状态、调整情感劝说目标、产生情感劝说行为四个阶段;其次针对这四个阶段,结合OCC情感模型和PAD心情模型,运用多属性效用理论,引入情感淡化因子和情感评价因子,定义了Agent情感触发函数,建立了八种Agent基本情感与劝说目标的映射关系,将Agent的情感劝说行为分为奖励型、申辩型、威胁型和反辩型四类,分别构建了相应的决策模型,从而构成了更加完整和合理的基于Agent的情感劝说的决策过程模型;最后通过算例证明了模型的合理性和有效性。

关键词： Agent 情感劝说决策过程决策模型

Utilizing engineered extracellular vesicles as delivery vectors in the management of ischemic stroke:a special outlook on mitochondrial delivery

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Neural Regeneration Research 2025年第8期20卷 2181-2198页

作者： jiali Chen Yiyang Li Xingping Quan Jinfen Chen Yan han Li Yang Manfei Zhou Greta Seng Peng Mok Ruibing Wang Yonghua Zhao Institute of Chinese Medical Sciences State Key Laboratory of Quality Research in Chinese MedicineUniversity of MacaoTaipaMacao Special Administrative RegionChina Department of Pharmacy Hunan Provincial People’s Hospitalthe First Affiliated Hospital of Hunan Normal UniversityChangshaHunan ProvinceChina Department of Electrical and Computer Engineering University of MacaoTaipaMacao Special Administrative RegionChina Department of Pharmaceutical Sciences Faculty of Health SciencesUniversity of MacaoTaipaMacao Special Administrative RegionChina

Ischemic stroke is a secondary cause of mortality worldwide,imposing considerable medical and economic burdens on *** vesicles,serving as natural nanocarriers for drug delivery,exhibit excellent biocompatibility in vivo and have significant advantages in the management of ischemic ***,the uncertain distribution and rapid clearance of extracellular vesicles impede their delivery *** utilizing membrane decoration or by encapsulating therapeutic cargo within extracellular vesicles,their delivery efficacy may be greatly ***,previous studies have indicated that microvesicles,a subset of large-sized extracellular vesicles,can transport mitochondria to neighboring cells,thereby aiding in the restoration of mitochondrial function post-ischemic *** extracellular vesicles have also demonstrated the capability to transfer mitochondrial components,such as proteins or deoxyribonucleic acid,or their sub-components,for extracellular vesicle-based ischemic stroke *** this review,we undertake a comparative analysis of the isolation techniques employed for extracellular vesicles and present an overview of the current dominant extracellular vesicle modification *** the complex facets of treating ischemic stroke,we also delineate various extracellular vesicle modification approaches which are suited to different facets of the treatment ***,given the burgeoning interest in mitochondrial delivery,we delved into the feasibility and existing research findings on the transportation of mitochondrial fractions or intact mitochondria through small extracellular vesicles and microvesicles to offer a fresh perspective on ischemic stroke therapy.

关键词： delivery engineering extracellular vesicles identification ischemic stroke isolation mitochondria targeting strategy therapeutic effects

贫困地区政府主导的农贷资源注入能够有效减贫吗?——基于连片特困地区微观农户调查

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经济科学 2019年第1期 108-119页

作者：王汉杰温涛韩佳丽西南大学经济管理学院重庆400716 西南政法大学经济学院重庆401120

世界各国的理论研究与实践经验均表明,金融扶贫是实现贫困人口脱贫的重要途径,但其功能的有效发挥依赖于一定的基础性条件。连片特困地区作为我国贫困人口的主要分布地,是新阶段脱贫攻坚的主战场。因此,中央政府高度重视连片特困地区农... 详细信息

世界各国的理论研究与实践经验均表明,金融扶贫是实现贫困人口脱贫的重要途径,但其功能的有效发挥依赖于一定的基础性条件。连片特困地区作为我国贫困人口的主要分布地,是新阶段脱贫攻坚的主战场。因此,中央政府高度重视连片特困地区农村金融扶贫功能的发挥,并注入了大量的农贷资源,然而,其对农户减贫的实际效应尚未得到真实反映。基于此,本文在理论分析的基础上,运用我国具有代表性的连片特困地区微观农户调查数据进行实证分析,结果发现:连片特困地区政府主导的农村正规信贷资源注入及其所带动的农村非正规信贷,不仅无法有效减缓贫困,而且扩大了农户内部的收入差距;而农户人力资本、物质资本以及社会资本的培育则具有积极的减贫作用。显然,本文的研究结论对于连片特困地区金融扶贫政策的调整具有一定的参考价值。

关键词：贫困地区政府主导农贷资源减贫