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

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

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Ferrihydrite transformation impacted by coprecipitation of lignin:Inhibition or facilitation?

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Journal of Environmental Sciences 2024年第5期139卷 23-33页

作者： Lin Liu Zhihui Yang Weichun Yang Wen Jiang qi Liao Mengying si Feiping Zhao School of Metallurgy and Environment Central South UniversityChangsha 410083China Chinese National Engineering Research Center for Control&Treatment of Heavy Metal Pollution(CNERC-CTHMP) Changsha 410083China

Lignin is a common soil organic matter that is present in soils,but its effect on the transformation of ferrihydrite(Fh)remains unclear.Organic matter is generally assumed to inhibit Fh transformation.However,lignin can reduce Fh to Fe(Ⅱ),in which Fe(Ⅱ)-catalyzed Fh transformation occurs.Herein,the effects of lignin on Fh transformation were investigated at 75℃ as a function of the lignin/Fh mass ratio(0-0.2),pH(4-8)and aging time(0-96 hr).The results of Fh-lignin samples(mass ratios=0.1)aged at different pH values showed that for Fh-lignin the time of Fh transformation into secondary crystalline minerals was significantly shortened at pH 6 when compared with pure Fh,and the Fe(Ⅱ)-accelerated transformation of Fh was strongly dependent on pH.Under pH 6,at low lignin/Fh mass ratios(0.05-0.1),the time of secondary mineral formation decreased with increasing lignin content.For high lignosulfonate-content material(lignin:Fh=0.2),Fh did not transform into secondary minerals,indicating that lignin content plays a major role in Fh transformation.In addition,lignin affected the pathway of Fh transformation by inhibiting goethite formation and facilitating hematite formation.The effect of coprecipitation of lignin on Fh transformation should be useful in understanding the complex iron and carbon cycles in a soil environment.

关键词： Ferrihydrite transformation Lignin Hematite Goethite Fe(Ⅱ)-catalyzed Reactive Fe(Ⅲ)species

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Review of the Analysis and Suppression for High-frequency Oscillations of the Grid-connected Wind Power Generation System

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CES Transactions on Electrical Machines and Systems 2024年第2期8卷 127-142页

作者： Bo pang qi si Pan Jiang Kai Liao Xiaojuan Zhu Jianwei Yang Zhengyou He the College of Electrical Engineering Southwest Jiaotong UniversityChengdu 610031China

High-frequency oscillation(HFO)of gridconnected wind power generation systems(WPGS)is one of the most critical issues in recent years that threaten the safe access of WPGS to the grid.Ensuring the WPGS can damp HFO is becoming more and more vital for the development of wind power.The HFO phenomenon of wind turbines under different scenarios usually has different mechanisms.Hence,engineers need to acquire the working mechanisms of the different HFO damping technologies and select the appropriate one to ensure the effective implementation of oscillation damping in practical engineering.This paper introduces the general assumptions of WPGS when analyzing HFO,systematically summarizes the reasons for the occurrence of HFO in different scenarios,deeply analyses the key points and difficulties of HFO damping under different scenarios,and then compares the technical performances of various types of HFO suppression methods to provide adequate references for engineers in the application of technology.Finally,this paper discusses possible future research difficulties in the problem of HFO,as well as the possible future trends in the demand for HFO damping.

关键词： Damping method High-frequency oscillation Stability Wind power generation

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Efficacy and safety of Yangxinshi tablet for chronic heart failure:A systematic review and meta-analysis

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World Journal of Clinical Cases 2024年第13期12卷 2218-2230页

作者： Sheng-Hua Lu Yun-Feng Yu si-si Dai Ya-qi Hu Jian-He Liu The First Clinical College of Chinese Medicine Hunan University of Chinese MedicineChangsha 410007Hunan ProvinceChina Branch of National Clinical Research Center for Chinese Medicine Cardiology The First Hospital of Hunan University of Chinese MedicineChangsha 410007Hunan ProvinceChina

BACKGROUND The specific benefits of Yangxinshi tablet(YXST)in the treating chronic heart failure(CHF)remain uncertain.AIM To systematically evaluate the efficacy and safety of YXST in the treatment of CHF.METHODS Randomized controlled trials(RCTs)investigating YXST for CHF treatment were retrieved from eight public databases up to November 2023.Meta-analyses of the included clinical studies were conducted using Review Manager 5.3.RESULTS Twenty RCTs and 1845 patients were included.The meta-analysis results showed that the YXST combination group,compared to the conventional drug group,significantly increased the clinical efficacy rate by 23%[relative risk(RR)=1.23,95%CI:1.17-1.29],(Psignificant publication bias(P=0.557).CONCLUsiON YXST effectively improves clinical symptoms and cardiac function in patients with CHF while maintaining a favorable safety profile,suggesting its potential as a therapeutic strategy for CHF.

关键词： Yangxinshi tablet Chronic heart failure Cardiac function Systematic evaluation Meta-analysis

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dECM restores macrophage immune homeostasis and alleviates iron overload to promote DTPI healing

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Regenerative Biomaterials 2024年第2期3卷 100-113页

作者： Ju Zhang Ruijuan si Yu Gao Hui Shan qi Su Zujian Feng Pingsheng Huang Deling Kong Weiwei Wang Tianjin Key Laboratory of Biomaterial Research Institute of Biomedical EngineeringChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin300192China School of Nursing Qingdao UniversityNingde RoadShinan DistrictQingdaoShandong266071China Cancer Hospital of Tianjin Medical University North Huanhu West RoadTianjinChina The Affliated Hospital of qingdao University 16 Jjiangsu RoadShinan DistrictQingdaoChina 5NankaiUniver aniin300071.China

Due to its highly insidious and rapid progression,deep tissue pressure injury(DTPI)is a clinical challenge.Our previous study found that DTPI may be a skeletal muscle injury dominated by macrophage immune dysfunction due to excessive iron accu-mulation.Decellularized extracellular matrix(dECM)hydrogel promotes skeletal muscle injury repair.However,its role in po-larizing macrophages and regulating iron metabolism in DTPI remains unclear.Here,porcine dECM hydrogel was prepared,and its therapeutic function and mechanism in repairing DTPI were investigated.The stimulus of dECM hydrogel toward RAW264.7 cells resulted in a significantly higher percentage of CD2o6+macrophages and notably decreased intracellular divalent iron levels.In mice DTPI model,dECM hydrogel treatment promoted M1 to M2 macrophage conversion,improved iron metabolism and reduced oxidative stress in the early stage of DTPI.In the remodeling phase,the dECM hydrogel remarkably enhanced revascularization and accelerated skeletal muscle repair.Furthermore,the immunomodulation of dEcM hydrogels in vivo was mainly involved in the P13k/Akt signaling pathway,as revealed by GO and KEGG pathway analysis,which may ameliorate the iron deposition and promote the healing of DTPI.Our findings indicate that dECM hydrogel is promising in skeletal muscle repair,inflammation resolution and tissue injury healing by effectively restoring macrophage immune homeostasis and normalizing iron metabolism.

关键词： Deep tissue pressure injury hydrogel immunomodulation tissue repair

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Shengmaisan combined with Liuwei Dihuang Decoction alleviates chronic intermittent hypoxia-induced cognitive impairment by activating the EPO/EPOR/JAK2 signaling pathway

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Chinese Journal of Natural Medicines 2024年第5期22卷 426-440页

作者： si Jianchao CHEN Xue qi Kerong LI Dongli LIU Bingbing ZHENG Yuying JI Ensheng YANG Shengchang Department of Physiology Hebei University of Chinese MedicineShijiazhuang 050000China Hebei Technology Innovation Center of TCM Combined Hydrogen Medicine Shijiazhuang 050000China Department of Geriatrics First People’s Hospital of XiaoganXiaogan 432000China

Chronic intermittent hypoxia(CIH),a principal pathophysiological aspect of obstructive sleep apnea(OSA),is associated with cognitive deficits.Clinical evidence suggests that a combination of Shengmaisan and Liuwei Dihuang Decoctions(SMS-LD)can enhance cognitive function by nourishing yin and strengthening the kidneys.This study aimed to assess the efficacy and underlying mechanisms of SMS-LD in addressing cognitive impairments induced by CIH.We exposed C57BL/6N mice to CIH for five weeks(20%-5%O_(2),5 min/cycle,8 h/day)and administered SMS-LD intragastrically(15.0 or 30 g·kg^(-1)·day)30 min before each CIH session.Additionally,AG490,a JJanus kinase 2(JAK2)inhibitor,was administered via intracerebroventricular injection.Cognitive function was evaluated using the Morris water maze,while synaptic and mitochondrial structures were examined by transmission electron microscopy.Oxidative stress levels were determined using DHE staining,and the activation of the erythropoietin(ER)/ER receptor(EPOR)/JAK2 signaling pathway was analyzed through immunohistochemistry and Western blotting.To further investigate molecular mechanisms,HT22 cells were treated in vitro with either SMS-LD medicated serum alone or in combination with AG490 and then exposed to CIH for 48 h.Our results indicate that SMS-LD significantly mitigated CIH-induced cognitive impairments in mice.Specifically,SMS-LD treatment enhanced dendritic spine density,ameliorated mitochondrial dysfunction,reduced oxidative stress,and activated the EPO/EPOR/JAK2 signaling pathway.Conversely,AG490 negated SMS-LD’s neuroprotective and cognitive improvement effects under CIH conditions.These findings suggest that SMS-LD’s beneficial impact on cognitive impairment and synaptic and mitochondrial integrity under CIH conditions may predominantly be attributed to the activation of the EPO/EPOR/JAK2 signaling pathway.

关键词： Chronic intermittent hypoxia Cognitive impairment Shengmaisan Liuwei Dihuang Decoction Oxidative stress EPO/EPOR/JAK2 signaling pathway

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Predictors of complications after prophylactic ileostomy reversal for rectal cancer:A retrospective study

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World Journal of Gastrointestinal Surgery 2024年第5期16卷 1354-1362页

作者： Quan Lv Xin-Peng Shu Dong Peng si-qi Li Zheng Xiang Department of Gastrointestinal Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Chongqing Key Laboratory of Department of General Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China

BACKGROUND Previous studies have analyzed the risk factors for complications after ileostomy reversal for rectal cancer(RC),but there were significant differences in the reported risk factors for complications after stoma reversal.No studies have analyzed the risk factors for stoma-related complications and overall postoperative com-plications separately.AIM To analyze the risk factors for overall complications and stoma-related complications after ileostomy reversal for patients with RC.METHODS This was a retrospective study of 439 patients who underwent ileostomy reversal at a clinical center and were followed up between September 2012 and September 2022.Continuous variables are expressed as the mean±SD and were analyzed with independent-sample t tests,while frequency variables are expressed as n(%),and theχ2 test or Fisher’s exact test was used.Univariate and multivariate logistic regression analyses were used to identify predictors of overall complications and stoma-related complications.RESULTS The overall complication rate after ileostomy reversal was 11.4%.Patients with lower preoperative albumin concentration(Psis of the study showed that a higher body mass index(BMI)(Psion(P=0.049),time from primary surgery to ileostomy reversal(Psion analysis revealed that a lower preoperative albumin level(Psis revealed that BMI(PsiON The pre

关键词： Ileostomy Reversal Risk factors Complications Rectal cancer

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Ferroptosis contributes to JEV-induced neuronal damage and neuroinflammation

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Virologica sinica 2024年第1期39卷 144-155页

作者： Wenjing Zhu qi Li Yong Yin Huanchun Chen Youhui si Bibo Zhu Shengbo Cao Zikai Zhao Jing Ye National Key Laboratory of Agricultural Microbiology Huazhong Agricultural UniversityWuhan430070China Frontiers Science Center for Animal Breeding and Sustainable Production Huazhong Agricultural UniversityWuhan430070China The Cooperative Innovation Center for Sustainable Pig Production Huazhong Agricultural UniversityWuhan430070China Hubei Hongshan Laboratory Wuhan430070China

Ferroptosis is a newly discovered prototype of programmed cell death (PCD) driven by iron-dependent phospholipid peroxidation accumulation, and it has been linked to numerous organ injuries and degenerative pathologies. Although studies have shown that a variety of cell death processes contribute to JEV-induced neuroinflammation and neuronal injury, there is currently limited research on the specific involvement of ferroptosis. In this study, we explored the neuronal ferroptosis induced by JEV infection in vitro and in vivo. Our results indicated that JEV infection induces neuronal ferroptosis through inhibiting the function of the antioxidant system mediated by glutathione (GSH)/glutathione peroxidase 4 (GPX4), as well as by promoting lipid peroxidation mediated by yes-associated protein 1 (YAP1)/long-chain acyl-CoA synthetase 4 (ACSL4). Further analyses revealed that JEV E and prM proteins function as agonists, inducing ferroptosis. Moreover, we found that treatment with a ferroptosis inhibitor in JEV-infected mice reduces the viral titers and inflammation in the mouse brains, ultimately improving the survival rate of infected mice. In conclusion, our study unveils a critical role of ferroptosis in the pathogenesis of JEV, providing new ideas for the prevention and treatment of viral encephalitis.

关键词： Japanese encephalitisvirus(JEV) Ferroptosis Neuron Lipid peroxidation Inflammatory response

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Association of prealbumin with short-term and long-term outcomes in patients with acute ST-segment elevation myocardial infarction

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Journal of Geriatric Cardiology 2024年第4期21卷 421-430页

作者： Jing TAN Jin si Ke-Ling XIAO Ying-Hua ZHANG qi HUA Jing LI Department of Cardiology Xuanwu Hospital Capital Medical UniversityBeijingChina Department of Geriatric Medicine Xuanwu Hospital Capital Medical UniversityNational Clinical Research Center for Geriatric DiseasesBeijingChina

BACKGROUND Prealbumin is considered to be a useful indicator of nutritional status. Furthermore, it has been found to be associated with severities and prognosis of a range of diseases. However, limited data on the association of baseline prealbumin level with outcomes of patients with acute ST-segment elevation myocardial infarction(STEMI) are available.METHODS We analyzed 2313 patients admitted for acute STEMI between October 2013 and December 2020. In-hospital outcomes and mortality during the 49 months(interquartile range: 26–73 months) follow-up period were compared between patients with the low prealbumin level(sity score matching, patients with the low prealbumin level than those with the high prealbumin level experienced higher incidences of heart failure with Killip class Ⅲ(9.9%vs. 4.4%, P = 0.034), cardiovascular death(8.4% vs. 3.4%, P = 0.035) and the composite of major adverse cardiovascular events(19.2%vs. 10.3%, P = 0.012). Multivariate logistic regression analysis identified that the low prealbumin level(sitivity = 0.544, specificity = 0.794). However, after multivariate adjustment of possible confounders, baseline prealbumin level(170 mg/L) was no longer independently associated with 49-month cardiovascular death. After propensity score matching, Kaplan-Meier survival curves revealed consistent results.CONCLUsiONS Decreased prealbumin level closely related to unfavorable short-term outcomes. However, after multivariate adjustment and controlling for baseline differences, baseline prealbumin level was not independently associated with an increased risk of long-term cardio

关键词： patients admitted infarction

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Analysis of Two Kinds of Stochastic Predator-prey Models with Stage Structure

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Acta Mathematicae Applicatae sinica 2024年

作者： Xin-qi WANG Tian-si ZHANG College of Science University of Shanghai for Science and Technology

In this paper, we studied a stochastic predator-prey model of two predators with stage structure.By constructing a suitable stochastic Lyapunov function, the condition of stationary distribution is verified, and we get the sufficient condition for the model to have ergodic stationary distribution. Then, by using the It?'s formula for the model, the sufficient conditions for the extinction of the predator population are given. Finally,some examples and numerical simulations are illustrated to verify the theoretical results.

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