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NQO1 Mediates Lenvatinib Resistance by Regulating ROS-induced Apoptosis in Hepatocellular Carcinoma

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Current Medical Science 2024年第1期44卷 168-179页

作者： Wei XUE Ting WANG Wen-jing tian si-qi PANG Hua-feng ZHANG Wei-dong jia Department of General Surgery The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China Institute of Health and Medicine Hefei Comprehensive National Science CenterHefei 230601China The Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease School of Basic Medical SciencesDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China

Objective Hepatocellular carcinoma(HCC)is the third leading cause of cancer-associated death worldwide.As a first-line drug for advanced HCC treatment,lenvatinib faces a significant hurdle due to the development of both intrinsic and acquired resistance among patients,and the underlying mechanism remains largely unknown.The present study aims to identify the pivotal gene responsible for lenvatinib resistance in HCC,explore the potential molecular mechanism,and propose combinatorial therapeutic targets for HCC management.Methods Cell viability and colony formation assays were conducted to evaluate the sensitivity of cells to lenvatinib and dicoumarol.RNA-Seq was used to determine the differences in transcriptome between parental cells and lenvatinib-resistant(LR)cells.The upregulated genes were analyzed by GO and KEGG analyses.Then,qPCR and Western blotting were employed to determine the relative gene expression levels.Afterwards,the intracellular reactive oxygen species(ROS)and apoptosis were detected by flow cytometry.Results PLC-LR and Hep3B-LR were established.There was a total of 116 significantly upregulated genes common to both LR cell lines.The GO and KEGG analyses indicated that these genes were involved in oxidoreductase and dehydrogenase activities,and reactive oxygen species pathways.Notably,NAD(P)H:quinone oxidoreductase 1(NQO1)was highly expressed in LR cells,and was involved in the lenvatinib resistance.The high expression of NQO1 decreased the production of ROS induced by lenvatinib,and subsequently suppressed the apoptosis.The combination of lenvatinib and NQO1 inhibitor,dicoumarol,reversed the resistance of LR cells.Conclusion The high NQO1 expression in HCC cells impedes the lenvatinib-induced apoptosis by regulating the ROS levels,thereby promoting lenvatinib resistance in HCC cells.

关键词： hepatocellular carcinoma lenvatinib resistance NAD(P)H quinone oxidoreductase 1 reactive oxygen species apoptosis dicoumarol

Medical services for sports injuries and illnesses in the Beijing 2022 Olympic Winter Games

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World Journal of Emergency Medicine 2022年第6期13卷 459-466页

作者： Peng-da Han Ding Gao Jie Liu Jing Lou Si-jia Tian Hui-xin Lian Sheng-mei Niu Lu-xi Zhang Yong Wang Jin-jun Zhang Emergence Medical Service Group for Beijing 2022 Olympic Winter Games Beijing Emergency Medical CenterBeijing 100031China Department of General Surgery Beijing Tongren HospitalCapital Medical UniversityBeijing 100730China Games Services Department Beijing Organizing Committee for the 2022 Olympic and Paralympic Winter GamesBeijing100041China

BACKGROUND:Beijing 2022 Olympic Winter Games was the second Games held amid the COVID-19 pandemic.To a certain extent,it has altered the way sporting activities operate.There is a lack of knowledge on injury risk and illness occurrence in elite winter sport athletes amid the COVID-19 pandemic.This study aimed to describe the incidence of injuries and illnesses sustained during the XXIV Olympic Winter Games in Beijing from February 4 to 20,2022.METHODS:We recorded the daily number of injuries and illnesses among athletes reported by Beijing 2022 medical staff in the polyclinic,medical venues,and ambulance.We calculated injury and illness incidence as the number of injuries or illnesses occurring during competition or training,respectively,with incidence presented as injuries/illnesses per 100 athlete-days.RESULTS:In total,2,897 athletes from 91 nations experienced injury or illness.Beijing 2022 medical staff reported 326 injuries and 80 illnesses,equaling 11.3 injuries and 2.8 illnesses per 100 athletes over the 17-day period.Altogether,11%of the athletes incurred at least one injury and nearly 3%incurred at least one illness.The number of injured athletes was highest in the skating sports(n=104),followed by alpine skiing(n=53),ice track(n=37),freestyle skiing(n=36),and ice hockey(n=35),and was the lowest in the Nordic skiing disciplines(n=20).Of the 326 injuries,14(4.3%)led to an estimated absence from training or competition of more than 1 week.A total of 52 injured athletes were transferred to hospitals for further care.The number of athletes with illness(n=80)was the highest for skating(n=33)and Nordic skiing(n=22).A total of 50 illnesses(62.5%)were admitted to the department of dentistry/ophthalmology/otolaryngology,and the most common cause of illness was other causes,including preexisting illness and medicine(n=52,65%).CONCLUsiON:Overall,11%of athletes incurred at least one injury during the Games,which is similar to the findings during the Olympic Winter Games in 2014 and 2018.Regarding illness,2%of athlet

关键词： Injuries Illnesses Olympic Winter Games Emergency medical service

Development and validation of novel models for the prediction of intravenous corticosteroid resistance in acute severe ulcerative colitis using logistic regression and machine learning

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Gastroenterology Report 2022年第1期10卷 498-506页

作者： si Yu Hui Li Yue Li Hui Xu Bei Tan Bo-Wen tian Yi-Min Dai Feng tian jia-Ming Qian Department of Gastroenterology Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijingP.R.China Department of Gastroenterology Shengjing Hospital of China Medical UniversityShenyangLiaoningP.R.China

Background The early prediction of intravenous corticosteroid(IVCS)resistance in acute severe ulcerative colitis(ASUC)patients remains an unresolved challenge.This study aims to construct and validate a model that accurately predicts IVCS resistance.Methods A retrospective cohort was established,with consecutive inclusion of patients who met the diagnosis criteria of ASUC and received IVCS during index hospitalization in Peking Union Medical College Hospital between March 2012 and January 2020.The primary outcome was IVCS resistance.Classification models,including logistic regression and machine learning-based models,were constructed.External validation was conducted in an independent cohort from Shengjing Hospital of China Medical University.Results A total of 129 patients were included in the derivation cohort.During index hospitalization,102(79.1%)patients responded to IVCS and 27(20.9%)failed;18(14.0%)patients underwent colectomy in 3 months;6 received cyclosporin as rescue therapy,and 2 eventually escalated to colectomy;5 succeeded with infliximab as rescue therapy.The Ulcerative Colitis Endoscopic Index of Severity(UCEIS)and C-reactive protein(CRP)level at Day 3 are independent predictors of IVCS resistance.The areas under the receiver-operating characteristic curves(AUROCs)of the logistic regression,decision tree,random forest,and extreme-gradient boosting models were 0.873(95%confidence interval[CI],0.704–1.000),0.648(95%CI,0.463–0.833),0.650(95%CI,0.441–0.859),and 0.604(95%CI,0.416–0.792),respectively.The logistic regression model achieved the highest AUROC value of 0.703(95%CI,0.473–0.934)in the external validation.Conclusions In patients with ASUC,UCEIS and CRP levels at Day 3 of IVCS treatment appeared to allow the prompt prediction of likely IVCS resistance.We found no evidence of better performance of machine learning-based models in IVCS resistance prediction in ASUC.A nomogrambased on the logistic regression model might aid in the management of ASUC patients.

关键词： acute severe ulcerative colitis steroid resistance colectomy machine learning

Constructing robust NiFe LDHs-NiFe alloy gradient hybrid bifunctional catalyst for overall water splitting:one-step electrodeposition and surface reconstruction

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Rare Metals 2023年第7期42卷 2272-2283页

作者： Yi-Fei Chen jia-Hong Li tian-tian Liu si-Hang You Peng Liu Fu-Jin Li Meng-Qi Gao Shu-Guang Chen Fei-Fei Zhang School of Materials Science and Engineering Changsha University of Science and TechnologyChangsha410114China Faculty of Engineering Department of Materials Science and EngineeringNational University of SingaporeSingapore117576Singapore School of Materials Science and Engineering Jilin UniversityChangchun130022China

NiFe layered double hydroxides(NiFe LDHs)have been intensively developed for the oxygen evolution reaction(OER)in alkaline media;however,their unsatisfactory hydrogen evolution reaction(HER)performance limits their practical application in overall water splitting.Herein,a simple and efficient one-step electrodeposition method is used to accomplish in situ growth of NiFe LDHsNiFe alloy gradient hybrid coatings on a carbon cloth(CC).Within the binder-free electrode,NiFe LDHs nanosheets with a low-crystalline nature exhibit highly active bifunctional OER/HER activities,and the NiFe alloy acts as a stable electron highway and strong skeleton bridge between NiFe LDHs and the CC.When the electrodes are simultaneously employed as the cathode and anode for overall water splitting,they require low cell potentials of 1.441 V at10 mA·cm^(-2)and 1.703 V at 100 mA·cm^(-2),respectively,and they demonstrate outstanding stability at a current density greater than 100 mA·cm^(-2)for more than 100 h.This is one of the best bifunctional OER and HER catalysts for overall water splitting.Both lattice defects and surface reconstructions crucially contribute to the bifunctional OER/HER activities of NiFe LDHs.This simple and scalable synthesis approach presents an intriguing paradigm for industrial production,and the fabricated electrode has potential application in high-current-density water splitting.

关键词： Bifunctional Electrodeposition Gradient hybrid NiFe layered double hydroxides(NiFe LDHs) Overall water splitting

A multi-modal clustering method for traditonal Chinese medicine clinical data via media convergence

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CAAI Transactions on Intelligence Technology 2023年第2期8卷 390-400页

作者： Jingna si Ziwei tian Dongmei Li Lei Zhang Lei Yao Wenjuan jiang jia Liu Runshun Zhang Xiaoping Zhang State Key Laboratory of Tree Genetics and Breeding College of Biological Sciences and TechnologyBeijing Forestry UniversityBeijingChina Department of Comparative Plant and Fungal Biology Wellcome Trust Millennium BuildingArdinglyUK School of Information Science and Technology Beijing Forestry UniversityBeijingChina Engineering Research Center for Forestry‐oriented Intelligent Information Processing National Forestry and Grassland AdministrationBeijingChina National Data Center of Traditional Chinese Medicine China Academy of Chinese Medical SciencesBeijingChina University of Wisconsin‐Milwaukee MilwaukeeWisconsinUSA Experimental Research Center China Academy of Chinese Medical SciencesBeijingChina Guang'anmen Hospital China Academy of Chinese Medical SciencesBeijingChina

Media convergence is a media change led by technological innovation.Applying media convergence technology to the study of clustering in Chinese medicine can significantly exploit the advantages of media fusion.Obtaining consistent and complementary information among multiple modalities through media convergence can provide technical support for clustering.This article presents an approach based on Media Convergence and Graph convolution Encoder Clustering(MCGEC)for traditonal Chinese medicine(TCM)clinical data.It feeds modal information and graph structure from media information into a multi-modal graph convolution encoder to obtain the media feature representation learnt from multiple modalities.MCGEC captures latent information from various modalities by fusion and optimises the feature representations and network architecture with learnt clustering labels.The experiment is conducted on real-world multimodal TCM clinical data,including information like images and text.MCGEC has improved clustering results compared to the generic single-modal clustering methods and the current more advanced multi-modal clustering methods.MCGEC applied to TCM clinical datasets can achieve better results.Integrating multimedia features into clustering algorithms offers significant benefits compared to single-modal clustering approaches that simply concatenate features from different modalities.It provides practical technical support for multi-modal clustering in the TCM field incorporating multimedia features.

关键词： graph convolutional encoder media convergence multi-modal clustering traditional Chinese medicine

Suberoylanilide hydroxamic acid upregulates reticulophagy receptor expression and promotes cell death in hepatocellular carcinoma cells

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世界胃肠病学杂志:英文版 2023年第34期29卷 5038-5053页

作者： jia-Yao Li tian tian Bing Han Ting Yang Yi-Xin Guo jia-Yu Wu Yu-si Chen Qin Yang Ru-jia Xie Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases College of Basic Medical SciencesGuizhou Medical UniversityGuiyang 550025Guizhou ProvinceChina Department of Pathophysiology College of Basic Medical SciencesGuizhou Medical UniversityGuiyang 550025Guizhou ProvinceChina Department of Eugenic Genetics Guiyang Maternal and Child Health Care HospitalGuiyang 550003Guizhou ProvinceChina

BACKGROUND Hepatocellular carcinoma(HCC)is a common clinical condition with a poor prognosis and few effective treatment options.Potent anticancer agents for treating HCC must be identified.Epigenetics plays an essential role in HCC tumorigenesis.Suberoylanilide hydroxamic acid(SAHA),the most common histone deacetylase inhibitor agent,triggers many forms of cell death in HCC.However,the underlying mechanism of action remains unclear.Family with sequence similarity 134 member B(FAM134B)-induced reticulophagy,a selective autophagic pathway,participates in the decision of cell fate and exhibits anticancer activity.This study focused on the relationship between FAM134B-induced reticulophagy and SAHA-mediated cell death.AIM To elucidate potential roles and underlying molecular mechanisms of reticulophagy in SAHA-induced HCC cell death.METHODS The viability,apoptosis,cell cycle,migration,and invasion of SAHA-treated Huh7 and MHCC97L cells were measured.Proteins related to the reticulophagy pathway,mitochondria-endoplasmic reticulum(ER)contact sites,intrinsic mitochondrial apoptosis,and histone acetylation were quantified using western blotting.ER and lysosome colocalization,and mitochondrial Ca^(2+)levels were characterized via confocal microscopy.The level of cell death was evaluated through Hoechst 33342 staining and propidium iodide colocalization.Chromatin immunoprecipitation was used to verify histone H4 lysine-16 acetylation in the FAM134B promoter region.RESULTS After SAHA treatment,the proliferation of Huh7 and MHCC97L cells was significantly inhibited,and the migration and invasion abilities were greatly blocked in vitro.This promoted apoptosis and caused G1 phase cells to increase in a concentration-dependent manner.Following treatment with SAHA,ER-phagy was activated,thereby triggering autophagy-mediated cell death of HCC cells in vitro.Western blotting and chromatin immunoprecipitation assays confirmed that SAHA regulated FAM134B expression by enhancing the histone H4 lysine-16 acetylation in the FAM134B pr

关键词： Suberoylanilide hydroxamic acid Histone H4 lysine-16 Reticulophagy Apoptosis Autophagic cell death Hepatocellular carcinoma

Estrogen receptor beta treats Alzheimer's disease

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Neural Regeneration Research 2013年第5期8卷 420-426页

作者： Zhu tian jia Fan Yang Zhao Sheng Bi Lihui si Qun Liu Department of Neurology the First Hospital of Jilin University Department of Neurology the Second Hospital of Jilin University Department of Obstetrics and Gynecology the Second Hospital of Jilin University

In vitro studies have shown that estrogen receptor β can attenuate the cytotoxic effect of amyloid protein on PC12 cells through the Akt pathway without estrogen stimulation. In this study, we aimed to observe the effect of estrogen receptor β in Alzheimer＇s disease rat models established by intraventricular injection of amyloid β protein. Estrogen receptor β lentiviral particles delivered via intraventricular injection increased Akt content in the hippocampus, decreased interleukin-1β mRNA tumor necrosis factor a mRNA and amyloid β protein levels in the hippocampus, and improved the learning and memory capacities in AIzheimer＇s disease rats. Estrogen receptor β short hairpin RNA lentiviral particles delivered via intraventricular injection had none of the above impacts on AIzheimer＇s disease rats. These experimental findings indicate that estrogen receptor β, independent from estrogen, can reduce inflammatory reactions and amyloid β deposition in the hJppocampus of AIzheimer＇s disease rats, and improve learning and memory capacities. This effect may be mediated through activation of the Akt pathway.

关键词： neural regeneration neurodegenerative diseases estrogen estrogen receptor β Alzheimer＇s disease amyloid β protein inflammatory cytokines Akt signaling pathway cognition neural protection photographs-containing paper neuroregeneration

A vehicle re-identification algorithm based on multi-sensor correlation

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Journal of Zhejiang University-Science C(Computers and Electronics) 2014年第5期15卷 372-382页

作者： Yin tian Hong-hui DONG Li-min jia si-yu LI State Key Laboratory of Rail Traffic Control and Safety Beijing Jiaotong University Shenzhen Graduate School Peking University

Magnetic sensors can be applied in vehicle recognition.Most of the existing vehicle recognition algorithms use one sensor node to measure a vehicle’s signature.However,vehicle speed variation and environmental disturbances usually cause errors during such a process.In this paper we propose a method using multiple sensor nodes to accomplish vehicle recognition.Based on the matching result of one vehicle’s signature obtained by different nodes,this method determines vehicle status and corrects signature segmentation.The co-relationship between signatures is also obtained,and the time offset is corrected by such a co-relationship.The corrected signatures are fused via maximum likelihood estimation,so as to obtain more accurate vehicle signatures.Examples show that the proposed algorithm can provide input parameters with higher accuracy.It improves the average accuracy of vehicle recognition from 94.0%to 96.1%,and especially the bus recognition accuracy from 77.6%to 92.8%.

关键词： Vehicle re-identification Magnetic sensor network Correlation Cross matching

数字素养能缓解女性过度教育吗——基于家庭追踪调查数据的证据

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山西财经大学学报 2024年第4期46卷 28-40页

作者：田艳平李佳锶中南财经政法大学公共管理学院湖北武汉430073

利用中国家庭追踪调查的三期数据(CFPS2016、CFPS2018、CFPS2020),采用计量模型实证考察数字素养对女性过度教育的影响及其机制。结果表明:数字素养与女性过度教育之间存在显著负向关系,即数字素养水平的提高能有效缓解女性过度教育问题... 详细信息

利用中国家庭追踪调查的三期数据(CFPS2016、CFPS2018、CFPS2020),采用计量模型实证考察数字素养对女性过度教育的影响及其机制。结果表明:数字素养与女性过度教育之间存在显著负向关系,即数字素养水平的提高能有效缓解女性过度教育问题,从而促进女性就业质量提升;数字素养提高可通过纠正就业地空间错位、提高女性劳动参与率、弱化女性生物钟干扰三条路径优化女性受教育程度和工作职位不匹配的问题;数字素养对女性过度教育的影响存在显著的城乡异质性、年龄异质性和性别观念异质性。

关键词：数字素养女性过度教育就业地空间错位女性劳动参与率女性生物钟