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Neuroscience Bulletin 2021年第5期37卷 720-724页

作者： Ying Luan Richard Salvi Lijie Liu Chunqiang Lu Yun Jiao Tianyu Tang Haiqing Liu gao-jun teng Jiangsu Key Laboratory of Molecular and Functional Imaging Department of RadiologyZhongda HospitalMedical School of Southeast UniversityNanjing 210009China Center for Hearing and Deafness University at BuffaloState University of New YorkBuffalo 14214USA Department of Physiology Medical College of Southeast UniversityNanjing 210009China

Dear Editor,Approximately 500 million individuals suffer from hearing loss worldwide. The number of hearing-impaired individuals is estimated to increase to 900 million by 2050. The etiology of hearing loss is complex.

关键词： impaired auditory complex.

Gd-EOB-DTPA-enhanced magnetic resonance imaging for focal liver lesions in Chinese patients:a multicenter,open-label,phase Ⅲ study

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Hepatobiliary & Pancreatic Diseases International 2013年第6期12卷 607-616页

作者： Meng-Su Zeng Hui-Yi Ye Liang Guo Wei-jun Peng Jian-Ping Lu gao-jun teng Josy Breuer Yi Huan Ping Li Jian-Rong Xu Chang-Hong Liang Department of Radiology Zhongshan HospitalFudan UniversityNo.180 Fenglin Road Departmentof Radiology General Hospital of PLA Department of Radiology First Affiliated HospitalSoochowUniversity Department of Radiology Cancer HospitalFudan University Department of Radiology Changhai HospitalSecond Military MedicalUniversity Department of Radiology Zhongda HospitalSoutheast University Bayer HealthCare Bayer Schering Pharma AG Department of Radiology Xijing HospitalFourth Military MedicalUniversity Bayer HealthCare CompanyLtd Department of Radiology RenjiHospitalShanghai Jiaotong University Department of Radiology Guangdong General Hospital

BACKGROUND:Contrast agents help to improve visibility in magnetic resonance(MR)imaging.However,owing to the large interstitial spaces of the liver,there is a reduction in the natural contrast gradient between lesions and healthy tissue.This study was undertaken to evaluate the efficacy and safety of the liverspecific MR imaging contrast agent gadoxetate disodium(GdEOB-DTPA)in Chinese patients.METHODS:This was a single-arm,open-label,multicenter study in patients with known or suspected focal liver lesions referred for contrast-enhanced MR imaging.MR imaging was performed in 234 patients before and after a single intravenous bolus of Gd-EOB-DTPA(0.025 mmol/kg body weight).Images were evaluated by clinical study investigators and three independent,blinded radiologists.The primary efficacy endpoint was sensitivity in lesion detection.RESULTS:Gd-EOB-DTPA improved sensitivity in lesion detection by 9.46%compared with pre-contrast imaging for the average of the three blinded readers(94.78%vs 85.32%for Gd-EOB-DTPA vs pre-contrast,respectively).Improvements in detection were more pronounced in lesions less than 1cm.Gd-EOB-DTPA improved diagnostic accuracy in lesion classification.CONCLUSIONS:This open-label study demonstrated that Gd-EOB-DTPA improves diagnostic sensitivity in liver lesions,particularly in those smaller than 1 cm.Gd-EOB-DTPA also significantly improves the diagnostic accuracy in lesion classification,and furthermore,Gd-EOB-DTPA is safe in Chinese patients with liver lesions.

关键词： gadoxetate disodium magnetic resonance imaging liver focal liver lesions

Re-evaluating Transarterial Chemoembolization Failure/Refractoriness:A Survey by Chinese College of Interventionalists

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Journal of Clinical and Translational Hepatology 2021年第4期9卷 521-527页

作者： Bin-Yan Zhong Wan-Sheng Wang Shen Zhang Hai-Dong Zhu Lei Zhang Jian Shen Xiao-Li Zhu gao-jun teng Cai-Fang Ni Department of Interventional Radiology the First Affiliated Hospital of Soochow UniversitySuzhouJiangsuChina Center of Interventional Radiology&Vascular Surgery Department of RadiologyZhongda HospitalMedical SchoolSoutheast UniversityNanjingJiangsuChina

Background and Aims:The recognition of transarterial chemoembolization(TACE)failure/refractoriness among Chinese clinicians remains unclear.Using an online survey conducted by the Chinese College of Interventionalists(CCI),the aim of this study was to explore the recognition of TACE failure/refractoriness and review TACE application for hepatocellular carcinoma(HCC)treatment in clinical practice.Methods:From 27 August 2020 to 30 August 2020 during the CCI 2020 annual meeting,a survey with 34 questions was sent by email to 264 CCI clinicians in China with more than 10 years of experience using TACE for HCC treatment.Results:A total of 257 clinicians participated and responded to the survey.Most participants agreed that the concept of“TACE failure/refractoriness”has scientific and clinical significance(n=191,74.3%).Nearly half of these participants chose TACE-based combination treatment as subsequent therapy after so-called TACE failure/refractoriness(n=88,46.1%).None of the existing TACE failure/refractoriness definitions were widely accepted by the participants;thus,it is necessary to re-define this concept for the treatment of HCC in China(n=235,91.4%).Most participants agreed that continuing TACE should be performed for patients with preserved liver function,presenting portal vein tumor thrombosis(n=242,94.2%)or extrahepatic spread(n=253,98.4%),after the previous TACE treatment to control intrahepatic lesion(s).Conclusions:There is an obvious difference in the recognition of TACE failure/refractoriness among Chinese clinicians based on existing definitions.Further work should be carried out to re-define TACE failure/refractoriness.

关键词： Hepatocellular carcinoma TACE Failure Refractoriness Survey

Clinical practice of transarterial chemoembolization for hepatocellular carcinoma:consensus statement from an international expert panel of International Society of Multidisciplinary Interventional Oncology(ISMIO)

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Hepatobiliary Surgery and Nutrition 2021年第5期10卷 661-671页

作者： Jian Lu Ming Zhao Yasuaki Arai Bin-Yan Zhong Hai-Dong Zhu Xiao-Long Qi Thierry de Baere Uei Pua Hyun Ki Yoon David C.Madoff gao-jun teng International Society of Multidisciplinary Interventional Oncology(ISMIO) Center of Interventional Radiology&Vascular Surgery Department of RadiologyZhongda HospitalMedical SchoolSoutheast UniversityNanjingChina State Key Laboratory of Oncology in Southern China GuangzhouChina Minimally Invasive&Interventional Department Cancer CenterSun Yat-sen UniversityGuangzhouChina Department of Diagnostic Radiology National Cancer CenterTokyoJapan Department of Interventional Radiology The First Affiliated Hospital of Soochow UniversitySuzhouChina CHESS Frontier Center First Hospital of Lanzhou UniversityLanzhouChina Gustave Roussy-Cancer Campus VillejuifFrance Department of Radiology Tan Tock Seng HospitalNational University of SingaporeSingaporeSingapore Department of Radiology and Research Institute of Radiology University of Ulsan College of MedicineAsan Medical CenterSeoulKorea Department of Radiology and Biomedical Imaging Section of Interventional Radiology and Department of Internal MedicineSection of Medical OncologyYale School of MedicineNew HavenCTUSA 不详

Importance:Transarterial chemoembolization(TACE)has been associated with a wide range of practice variations for hepatocellular carcinoma(HCC)between the East and the West.This considerable ambiguity may lead to the heterogeneous quality in treatment and have a negative impact on the role of TACE in the overall multidisciplinary HCC treatment system.Objective:It may be a good start to establish a guideline worldwide to have this consensus from experts who represent east and west,although it does not cover all aspects of TACE.Evidence Review:An international expert panel on TACE is convened to cluster the expert’s opinions and summary a standard consensus.This panel committee consist of leading physicians in TACE on HCC from USA,France,Japan,Singapore,Korea,China,and so on.The first-round face-to-face consensus meeting was held during in Nanjing,China in October 2019.The second-round conference for revision of the consensus was held during the Annual Meeting of Chinese College of Interventionalists in August 2020 by a hybrid format of a Webinar and roundtable meeting.After several on-line revisions,the final manuscript was approved by all members of the panel in june 2021.Findings:The consensus statements were organized into the following categories:patients’selection,performing the procedure,TACE outcomes,repeat TACE,TACE failure/refractory,and TACE-based combination treatments.Conclusions and Relevance for Reviews:More and more evidences have showed the better outcomes with strategy of combined TACE with other local therapies such as ablations.The most-recently developing strategy of combined TACE with PD-1/PD-L1 plus tyrosine kinase inhibitor(TKI)agents has shined a light to the HCC patients,especially to those with high risk of tumor recurrence after treatment or TACE failure/refractory.

关键词： Transarterial chemoembolization(TACE) hepatocellular carcinoma(HCC) consensus

Prognostic nomogram on admission predicting progression for patients with nonsevere COVID-19

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Fundamental Research 2021年第2期1卷 111-116页

作者： Zhi Wang Bin-Yan Zhong Hui Dai Qiu-Zhen Xu Wei-Bin Yang Xin Zhang Chuan-jun Xu Jin-Er Shu Biao Shi Chu-Hui Zeng Cheng Li Jian-Song Ji Yong-Gang Li gao-jun teng Jiangsu Key Laboratory of Molecular and Funetional Imaging Deparment of RadiologyZhongda HospitalSoutheast UntversityNanjing Jiangsu Province 210009China Department of Interventional Radiology The First Affiliated Hospital of Soochow UniversitySuzhouJiangsu Province 215006China Department of Radiology The First Affiliated Hospital of Soochow UniversitySuzhouJiangsu Province 215006China Institute of Medical Imaging Soochow UniversitySuzhouJiangsu Province 215006China Department of Radiology Lishui Central Hospital Wenzhou Medical CollegeLishuiZhejiang Province 323000China Department of Medical Imaging The Fourth People's Hospital of HuaianHuaianJiangsu Province 223002China Department of Radiology the Second Hospital of NanjingNanjing University of Chinese MedicineNanjingJiansu Province 210003China Deprtment of Radiology Jinhua Hospial of Zhejiang UntversityJinhuaZhejiang Province 321001China CT Depertment Bengbu First People's HospitalBengbu Medical CollegeBengbuArhui Province 233000China

The present study aimed to establish a prognostic nomogram to stratify high-risk patients with Coronavirus Disease 2019(COVID-19)who progressed from the nonsevere condition on admission to severe during hospitalization.This multicenter retrospective study included patients with nonsevere COVID-19 on admission from Jan 10,2020 to Feb 7,2020.In the training cohort,independent risk factors associated with disease progression were identified by univariate and multivariate analyses.The prognostic nomogram was established and then validated externally using C-index.The study included 351 patients(293 and 58 in the training and validation cohorts,respectively),with 27(9.2%)and 5(8.6%)patients progressed,respectively.In the training cohort,older age(OR 1.036,95%Cl 1.000-1.073),more lobes involved on chest CT(OR 1.841,95%Cl 1.117-3.035),comorbidity present(OR 2.478,95%Cl 1.020-6.018),and lower lymphocyte count(OR 0.081,95%Cl 0.019-0.349)were identified as independent risk factors.The prognostic nomogram was established in the training cohort with satisfied external prognostic performance(C-index 0.906,95%Cl 0.806-1.000).In conclusion,older age,comorbidity present,more lobes involved on chest CT,and lower lymphocyte count are independent risk factors associated with disease progression during hospitalization for patients with nonsevere COVID-19.

关键词： COVID-19 Severe disease Progression Nomogram Risk factor

Caseinolytic mitochondrial matrix peptidase X is essential for homologous chromosome synapsis and recombination during meiosis of male mouse germ cells

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Asian Journal of Andrology 2024年第2期26卷 165-174页

作者： Hai-Wei Feng Yu Zhao Yan-Ling gao Dong-teng Liu Li-jun Huo Key Laboratory of Agricultural Animal Genetics Breeding and ReproductionEducation Ministry of ChinaCollege of Animal Science and TechnologyHuazhong Agricultural UniversityWuhan 430070China Shenzhen Key Laboratory of Fertility Regulation Reproductive Medicine CenterThe University of Hong Kong-Shenzhen HospitalShenzhen 518053China Maternal-Fetal Medicine Institute Department of Obstetrics and GynaecologyShenzhen Baoan Women's and Children's HospitalJinan UniversityShenzhen 518100China Department of Obstetrics and Gynaecology Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong SARChina

Meiosis is the process of producing haploid gametes through a series of complex chromosomal events and the coordinated action of various proteins.The mitochondrial protease complex(ClpXP),which consists of caseinolytic mitochondrial matrix peptidase X(ClpX)and caseinolytic protease P(ClpP)and mediates the degradation of misfolded,damaged,and oxidized proteins,is essential for maintaining mitochondrial homeostasis.ClpXP has been implicated in meiosis regulation,but its precise role is currently unknown.In this study,we engineered an inducible male germ cell-specific knockout caseinolytic mitochondrial matrix peptidase X(Clpx^(cKO))mouse model to investigate the function of ClpX in meiosis.We found that disrupting Clpx in male mice induced germ cell apoptosis and led to an absence of sperm in the epididymis.Specifically,it caused asynapsis of homologous chromosomes and impaired meiotic recombination,resulting in meiotic arrest in the zygotene-to-pachytene transition phase.The loss of ClpX compromised the double-strand break(DSB)repair machinery by markedly reducing the recruitment of DNA repair protein RAD51 homolog 1(RAD51)to DSB sites.This dysfunction may be due to an insufficient supply of energy from the aberrant mitochondria in Clpx^(cKO) spermatocytes,as discerned by electron microscopy.Furthermore,ubiquitination signals on chromosomes and the expression of oxidative phosphorylation subunits were both significantly attenuated in Clpx^(cKO) spermatocytes.Taken together,we propose that ClpX is essential for maintaining mitochondrial protein homeostasis and ensuring homologous chromosome pairing,synapsis,and recombination in spermatocytes during meiotic prophase I.

关键词： ClpX homologous chromosome meiosis mitochondrial recombination synapsis

Transarterial chemoembolization with PD-(L)1 inhibitors plus molecular targeted therapies for hepatocellular carcinoma(CHANCE001)

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Signal Transduction and Targeted Therapy 2023年第3期8卷 1198-1207页

作者： Hai-Dong Zhu Hai-Liang Li Ming-Sheng Huang Wei-Zhu Yang Guo-Wen Yin Bin-Yan Zhong jun-Hui Sun Zhi-Cheng Jin Jian-Jian Chen Nai-Jian Ge Wen-Bin Ding Wen-Hui Li Jin-Hua Huang Wei Mu Shan-Zhi Gu Jia-Ping Li Hui Zhao Shu-Wei Wen Yan-Ming Lei Yu-Sheng Song Chun-Wang Yuan Wei-Dong Wang Ming Huang Wei Zhao Jian-Bing Wu Song Wang Xu Zhu Jian-jun Han Wei-Xin Ren Zai-Ming Lu Wen-Ge Xing Yong Fan Hai-Lan Lin Zi-Shu Zhang Guo-Hui Xu Wen-Hao Hu Qiang Tu Hong-Ying Su Chuan-Sheng Zheng Yong Chen Xu-Ya Zhao Zhu-Ting Fang Qi Wang Jin-Wei Zhao Ai-Bing Xu Jian Xu Qing-Hua Wu Huan-Zhang Niu Jian Wang Feng Dai Dui-Ping Feng Qing-Dong Li Rong-Shu Shi Jia-Rui Li Guang Yang Hai-Bin Shi Jian-Song Ji Yu-E Liu Zheng Cai Po Yang Yang Zhao Xiao-Li Zhu Li-Gong Lu gao-jun teng Center of Interventional Radiology&Vascular Surgery Department of RadiologyZhongda HospitalMedical SchoolSoutheast UniversityNanjing 210009China Department of Minimally invasive Intervention The Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450008China Department of Interventional Radiology the Third Affiliated HospitalSun Yat-Sen UniversityGuangzhou 510630China Department of Interventional Radiology Union Hospital of Fujian Medical UniversityFuzhou 350001China Department of Interventional Radiology Jiangsu Cancer Hospital&Jiangsu Institute of Cancer Research&The Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing 210009China Department of Interventional Radiology The First Affiliated Hospital of Soochow UniversitySoochow UniversitySuzhou 215006China Hepatobiliary and Pancreatic Interventional Treatment Center Division of Hepatobiliary and Pancreatic SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Department of Interventional Radiology Eastern Hospital of Hepatobiliary SurgeryNavy Medical University(Second Military Medical University)Shanghai 200438China Department of Interventional Radiology Nantong First People’s HospitalNantong 226001China Department of Interventional Radiology Yancheng Third People’s HospitalYancheng 224008China Department of Minimally Invasive Interventional Therapy Sun YatSen University Cancer CenterGuangzhou 510060China Department of Vascular Surgery Southwest HospitalThird Military Medical University(Army Medical University)Chongqing 400038China. Department of Interventional Radiology Hunan Cancer HospitalChangsha 410031China Department of Interventional Oncology The First Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510080China Department of Interventional Radiology The Hospital of Nantong UniversityNantong 226001China Department of Interventional Therapy Shanxi Tumor HospitalTaiyuan 030001China Department of Interventional Radiology Tibet Autonomous Region People’s

There is considerable potential for integrating transarterial chemoembolization(TACE),programmed death-(ligand)1(PD-[L]1)inhibitors,and molecular targeted treatments(MTT)in hepatocellular carcinoma(HCC).It is necessary to investigate the therapeutic efficacy and safety of TACE combined with PD-(L)1 inhibitors and MTT in real-world situations.In this nationwide,retrospective,cohort study,826 HCC patients receiving either TACE plus PD-(L)1 blockades and MTT(combination group,n=376)or TACE monotherapy(monotherapy group,n=450)were included from January 2018 to May 2021.The primary endpoint was progression-free survival(PFS)according to modified RECIST.The secondary outcomes included overall survival(OS),objective response rate(ORR),and safety.We performed propensity score matching approaches to reduce bias between two groups.After matching,228 pairs were included with a predominantly advanced disease population.Median PFS in combination group was 9.5 months(95%confidence interval[CI],8.4-11.0)versus 8.0 months(95%CI,6.6-9.5)(adjusted hazard ratio[HR],0.70,P=0.002).OS and ORR were also significantly higher in combination group(median OS,19.2[16.1-27.3]vs.15.7 months[13.0-20.2];adjusted HR,0.63,P=0.001;ORR,60.1%vs.32.0%;P<0.001).Grade 3/4 adverse events were observed at a rate of 15.8%and 7.5%in combination and monotherapy groups,respectively.Our results suggest that TACE plus PD-(L)1 blockades and MTT could significantly improve PFS,OS,and ORR versus TACE monotherapy for Chinese patients with predominantly advanced HCC in real-world practice,with an acceptable safety profile.

关键词： hepatocellular targeted matching

Distributed Source-Load-Storage Cooperative Low-Carbon Scheduling Strategy Considering Vehicle-to-Grid Aggregators

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Journal of Modern Power Systems and Clean Energy 2024年第2期12卷 440-453页

作者： Xiao Xu Ziwen Qiu teng Zhang Hui gao School of Automation Nanjing University of Posts and TelecommunicationsNanjing210023China

The vehicle-to-grid(V2G)technology enables the bidirectional power flow between electric vehicle(EV)batteries and the power grid,making EV-based mobile energy storage an appealing supplement to stationary energy storage systems.However,the stochastic and volatile charging behaviors pose a challenge for EV fleets to engage directly in multi-agent cooperation.To unlock the scheduling potential of EVs,this paper proposes a source-load-storage cooperative low-carbon scheduling strategy considering V2G aggregators.The uncertainty of EV charging patterns is managed through a rolling-horizon control framework,where the scheduling and control horizons are adaptively adjusted according to the availability periods of EVs.Moreover,a Minkowski-sum based aggregation method is employed to evaluate the scheduling potential of aggregated EV fleets within a given scheduling horizon.This method effectively reduces the variable dimension while preserving the charging and discharging constraints of individual EVs.Subsequently,a Nash bargaining based cooperative scheduling model involving a distribution system operator(DSO),an EV aggregator(EVA),and a load aggregator(LA)is established to maximize the social welfare and improve the low-carbon performance of the system.This model is solved by the alternating direction method of multipliers(ADMM)algorithm in a distributed manner,with privacy of participants fully preserved.The proposed strategy is proven to achieve the objective of low-carbon economic operation.

关键词： Electric vehicle(EV) low-carbon scheduling mobile storage system Nash bargaining power flexibility alternating direction method of multipliers(ADMM).

Biological effects of low-dose-rate irradiation of pancreatic carcinoma cells in vitro using ^(125)I seeds

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World Journal of Gastroenterology 2015年第8期21卷 2336-2342页

作者： Zhong-Min Wang Jian Lu Li-Yun Zhang Xiao-Zhu Lin Ke-Min Chen Zhi-Jin Chen Fen-Ju Liu Fu-Hua Yan gao-jun teng Ai-Wu Mao Department of Radiology Ruijin Hospital Luwan Branch Shanghai Jiao Tong University School of Medicine Institution of Molecular Imaging Southeast University Nanjing 210009 China Department of Radiology Ruijin Hospital Shanghai Jiao Tong University School of Medicine Soochow University School of Medicine Department of Radiobiology School of Radiological Medicine and Protection Soochow University Institution of Molecular Imaging Southeast University Department of Interventional Radiology Shanghai St. Luke’s Hospital

AIM:To determine the mechanism of the radiationinduced biological effects of 125I seeds on pancreatic carcinoma cells in vitro.METHODS:SW1990 and PANC-1 pancreatic cancer cell lines were cultured in DMEM in a suitable environment.Gray’s model of iodine-125(125I)seed irradiation was used.In vitro,exponential phase SW1990,and PANC-1cells were exposed to 0,2,4,6,and 8 Gy using 125I radioactive seeds,with an initial dose rate of 12.13c Gy/h.A clonogenic survival experiment was performed to observe the ability of the cells to maintain their clonogenic capacity and to form colonies.Cell-cycle and apoptosis analyses were conducted to detect the apoptosis percentage in the SW1990 and PANC-1 cells.DNA synthesis was measured via a tritiated thymidine(3H-Td R)incorporation experiment.After continuous low-dose-rate irradiation with 125I radioactive seeds,the survival fractions at 2 Gy(SF2),percentage apoptosis,and cell cycle phases of the SW1990 and PANC-1 pancreatic cancer cell lines were calculated and compared.RESULTS:The survival fractions of the PANC-1 andSW1990 cells irradiated with 125I seeds decreased exponentially as the dose increased.No significant difference in SF2 was observed between SW1990 and PANC-1 cells(0.766±0.063 vs 0.729±0.045,P<0.05).The 125I seeds induced a higher percentage of apoptosis than that observed in the control in both the SW1990and PANC-1 cells.The rate of apoptosis increased with increasing radiation dosage.The percentage of apoptosis was slightly higher in the SW1990 cells than in the PANC-1 cells.Dose-dependent G2/M cellcycle arrest was observed after 125I seed irradiation,with a peak value at 6 Gy.As the dose increased,the percentage of G2/M cell cycle arrest increased in both cell lines,whereas the rate of DNA incorporation decreased.In the 3H-Td R incorporation experiment,the dosimetry results of both the SW1990 and PANC-1cells decreased as the radiation dose increased,with a minimum at 6 Gy.There were no significant differences in the dosimetry results of the two cell lines when they

关键词： 125I radioactive seeds Biological effects Pancreat

Anthrax lethal toxin and tumor necrosis factor-a synergize on intestinal epithelia to induce mouse death

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Protein & Cell 2024年第2期15卷 135-148页

作者： Xinhe gao teng teng Yifei Liu Tingting Ai Rui Zhao Yilong Fu Peipei Zhang Jiahuai Han Yingying Zhang State Key Laboratory of Cellular Stress Biology School of Life SciencesFaculty of Medicine and Life SciencesXiamen UniversityXiamen 361102China Research Unit of Cellular Stress of CAMS Xiang'an Hospital of Xiamen UniversityCancer Research Center of Xiamen UniversitySchool of MedicineFaculty of Medicine and Life SciencesXiamen UniversityXiamen 361102China Laboratory Animal Center Faculty of Medicine and Life SciencesXiamen UniversityXiamen 361102China

Bacillus anthracis lethal toxin(LT)is a determinant of lethal anthrax.Its function in myeloid cells is required for bacterial dissemination,and LT itself can directly trigger dysfunction of the cardiovascular system.The interplay between LT and the host responses is important in the pathogenesis,but our knowledge on this interplay remains limited.Tumor necrosis factor-a(TNF-a)is a pleiotropic pro-inflammatory cytokine induced by bacterial infections.Since LT accumulates and cytokines,predominantly TNF,amass during B.anthracis infection,co-treatment of TNF+LT in mice was used to mimic in vivo conditions for LT to function in inflamed hosts.Bone marrow transplantation and genetically engineered mice showed unexpectedly that the death of intestinal epithelial cells(IECs)rather than that of hematopoietic cells led to LT+TNF-induced lethality.Inhibition of p38a mitogen-activated protein kinase(MAPK)signaling by LT in IECs promoted TNF-induced apoptosis and necroptosis of IECs,leading to intestinal damage and mouse death.Consistently,p38a inhibition by LT enhanced TNF-mediated cell death in human colon epithelial HT-29 cells.As intestinal damage is one of the leading causes of lethality in anthrax patients,the IEC damage caused by LT+TNF would most likely be a mechanism underneath this clinical manifestation and could be a target for interventions.

关键词： lethal toxin TNF p38a intestinal epithelial cell cell death