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Bavachin enhances NLRP3 inflammasome activation induced by ATP or nigericin and causes idiosyncratic hepatotoxicity

Frontiers of Medicine 2021年第4期15卷 594-607页

作者： Nan Qin Guang Xu Yan wang Xiaoyan Zhan Yuan Gao Zhilei wang Shubin Fu Wei Shi Xiaorong Hou Chunyu wang Ruisheng Li Yan Liu jiabo wang Haiping Zhao Xiaohe Xiao Zhaofang Bai China Military Institute of Chinese Materia the Fifth Medical CentreChinese PLA General HospitalBeijing 100039China Department of Pharmacy Nantong Hospital of Traditional Chinese MedicineNantong 226300China School of Pharmacy Henan University of Chinese MedicineZhengzhou 450046China School of Traditional Chinese Medicine Capital Medical UniversityBeijing 100069China Research Center for Clinical and Translational Medicine the Fifth Medical CentreChinese PLA General HospitalBeijing 100039China School of Traditional Chinese Medicine Jiangxi University of Traditional Chinese MedicineNanchang 330004China Integrative Medical Centre the Fifth Medical CentreChinese PLA General HospitalBeijing 100039China

Psoraleae Fructus(PF)is a well-known traditional herbal medicine in China,and it is widely used for osteoporosis,vitiligo,and other diseases in clinical ***,liver injury caused by PF and its preparations has been frequently reported in recent *** previous studies have demonstrated that PF could cause idiosyncratic drug-induced liver injury(IDILI),but the mechanism underlying its hepatotoxicity remains *** paper reports that bavachin isolated from PF enhances the specific stimuli-induced activation of the NLRP3 inflammasome and leads to *** boosts the secretion of IL-ip and caspase-1 caused by ATP or nigericin but not those induced by poly(I:C),monosodium urate crystal,or intracellular *** does not affect AIM2 or NLRC4 inflammasome ***,bavachin specifically increases the production of nigericin-induced mitochondrial reactive oxygen species among the most important upstream events in the activation of the NLRP3 *** increases the levels of aspartate transaminase and alanine aminotransferase in serum and hepatocyte injury accompanied by the secretion of IL-ip via a mouse model of lipopolysaccharide-mediated susceptibility to *** results suggest that bavachin specifically enhances the ATP-or nigericin-induced activation of the NLRP3 *** also potentially contributes to PF-induced idiosyncratic ***,bavachin and PF should be evaded among patients with diseases linked to the ATP-or nigericin-mediated activation of the NLRP3 inflammasome,which may be a dangerous factor for liver injury.

关键词： Psoraleae Fructus bavachin idiosyncratic drug-induced liver injury caspase-1 IL-lp NLRP3 inflammasome

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Icariside Ⅱ, a main compound in Epimedii Folium, induces idiosyncratic hepatotoxicity by enhancing NLRP3 inflammasome activation

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Acta Pharmaceutica Sinica B 2020年第9期10卷 1619-1633页

作者： Zhilei wang Guang Xu Hongbo wang Xiaoyan Zhan Yuan Gao Nian Chen Ruisheng Li Xueai Song Yuming Guo Ruichuang Yang Ming Niu jiabo wang Youping Liu Xiaohe Xiao Zhaofang Bai School of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu 611137China China Military Institute of Chinese Materia the Fifth Medical CentreChinese PLA General HospitalBeijing 100039China Department of Hepatobiliary Surgery Center the Fifth Medical CentreChinese PLA General HospitalBeijing 100039China School of Chinese Materia Medica Capital Medical UniversityBeijing 100029China Research Center for Clinical and Translational Medicine the Fifth Medical CentreChinese PLA General HospitalBeijing 100039China Integrative Medical Center the Fifth Medical CentreChinese PLA General HospitalBeijing 100039China

Idiosyncratic drus-induced liver injury(IDILI)is an intrequent but potentially serious disease that develops the main reason for post-marketing safety warnings and withdrawals of *** Folium(EF),the widely used herbal medicine,has shown to cause idiosyncratic liver injury,but the underlying mechanisms are poorly *** evidence has indicated that most cases of IDILI are immune ***,we report that icarisideⅡ(ICSⅡ),the major active and metabolic constituent of EF,causes idiosyncratic liver injury by promoting NLRP3 inflammasome ***Ⅱexacerbates NLRP3 inflammasome activation triggered by adenosine triphosphate(ATP)and nigericin,but not silicon dioxide(SiO2),monosodium urate(MSU)crystal or cytosolic lipopolysaccharide(LPS).Additionally,the activation of NLRC4 and AIM2 inflammasomes is not affected by ICSⅡ.Mechanistically,synergistic induction of mitochondrial reactive oxygen species(mtROS)is a crucial contributor to the enhancing effect of ICSⅡon ATP-or nigericin-induced NLRP3 inflammasome ***,in vivo data show that a combination of non-hepatotoxic doses of LPS and ICSⅡcauses the increase of aminotransferase activity,hepatic inflammation and pyroptosis,which is attenuated by Nlrp3 deficiency or pretreatment with MCC950(a specific NLRP3 inflammasome inhibitor).In conclusion,these findings demonstrate that ICSⅡcauses idiosyncratic liver injury through enhancing NLRP3 inflammasome activation and suggest that ICSⅡmay be a risk factor and responsible for EF-induced liver injury.

关键词： Epimedii Folium IcarisideⅡ Idiosyncratic drug-induced liver injury NLRP3 inflammasome Reactive oxygen species Mitochondria

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Clinical characteristics of 96 patients with drug-induced acute liver failure:a comparison between Traditional Chinese and Western Medicine

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Journal of Traditional Chinese Medicine 2017年第3期37卷 286-297页

作者： He Tingting Zhu Yun wang jiabo Gong Man wang Ruilin Niu Ming Jing Jing wang Lifu wang Zhongxia Zhang Ning Bai Zhaofang Bai Yunfeng Li Yonggang Xiao Xiaohe Medical School of Chinese PLA Integrative Medicine Center 302 Military HospitalBeijing 100039China Integrative Medicine Center 302 Military HospitalBeijing 100039China China Military Institute of Chinese Medicine 302 Military HospitalBeijing 100039China Medical School of Chinese People's LiberationArmy China Military Institute of Chinese Medicine 302 Military HospitalBeijing 100039China

OBJECTIVE: To compare the causes, clinical symptoms, laboratory test results, and prognosis in patients with acute liver failure(ALF) induced by traditional Chinese medicines(TCM) and by Western Medicines(WM).METHODS: The medical histories of patients who were diagnosed with drug-induced ALF(DALF)(n =96) after hospitalization in the 302 Military Hospital between January 2010 and December 2015 were retrospectively ***: Fifty-eight of the 96 DALF patients(60.4%) had a hepatocellular pattern of DALF, 16 patients(16.7%) had a cholestatic pattern, and 22 patients(22.9%) had a mixed pattern. DALF resolved in 24 patients(25.0%). Twenty-five patients(26.0%)developed chronic liver injury, 43 patients(44.8%)died, and 4 patients(4.2%) underwent liver transplantation. There were 42 ALF patients(43.8%) who received WM, and 32 ALF patients(33.3%) who received TCM. TCM-induced ALF patients had a higher average age [42.4 ± 18.4) vs(33.5 ± 17.9) years,P = 0.04] and higher creatinine and urine nitrogen levels [(155.2 ± 108.8) vs(97.5 ± 130.4) mmol/L, P =0.047;(9.1 ± 7.7) vs(4.3 ± 5.0) mmol/L, P = 0.002, respectively]. Patients with TCM-induced ALF exhibited an increased risk of renal injury [odds ratio(OR),3.75; 95% confidence interval(CI), 1.330-10.577].The 14 patients with TCM-induced ALF who died exhibited higher creatinine levels than the 18 patients with TCM-induced ALF patients who survived[(218.7 ± 111.6) vs(105.8 ± 78.4) mmol/L, P =0.002]. They were also more likely to exhibit ascites(85.7% vs 44.4%, P = 0.017) and hepatorenal syndrome(78.6% vs 22.2%, P = 0.002).CONCLUSION: TCM-induced ALF was more likely to be accompanied by renal injury than was WM-induced ALF, especially in TCM-induced ALF patients who died.

关键词： Drug-induced liver injury Jaundice, ob-structive Medicine, Chinese traditional Creatinine Hepatorenal syndrome

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T cell–associated immunoregulation and antiviral effect of oxymatrine in hydrodynamic injection HBV mouse model

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Acta Pharmaceutica Sinica B 2017年第3期7卷 311-318页

作者： Xiuxiu Sang Ruilin wang Yanzhong Han Cong’en Zhang Honghui Shen Zhirui Yang Yin Xiong Huimin Liu Shijing Liu Ruisheng Li Ruichuang Yang jiabo wang Xuejun wang Zhaofang Bai Xiaohe Xiao Chengde Medical College China Military Institute of Chinese Medicine 302 Military Hospital Integrative Medical Center 302 Military Hospital Department of Biotechnology Beijing Institute of Radiation Medicine Faculty of Life Science and Technology Kunming University of Science and Technology Research Center for Clinical&Translational Medicine 302 Military Hospital

Although oxymatrine(OMT) has been shown to directly inhibit the replication of hepatitis B virus(HBV) in vitro, limited research has been done with this drug in vivo. In the present study, the antiviral effect of OMT was investigated in an immunocompetent mouse model of chronic HBV *** infection was achieved by tail vein injection of a large volume of DNA solution. OMT(2.2, 6.7 and20 mg/kg) was administered by daily intraperitoneal injection for 6 weeks. The efficacy of OMT was evaluated by the levels of HBV DNA, hepatitis B surface antigen(HBs Ag), hepatitis B e antigen(HBe Ag)and hepatitis B core antigen(HBc Ag). The immunoregulatory activity of OMT was evaluated by serum ELISA and flow cytometry. Results shows that OMT at 20 mg/kg inhibited HBV replication, and it was more efficient than entecavir(ETV) in the elimination of serum HBs Ag and intrahepatic HBc Ag. Inaddition, OMT accelerated the production of interferon-γ(IFN-γ) in a dose-dependent manner in CD4^+T cells. Our findings demonstrate the beneficial effects of OMT on the enhancement of immunological function and in the control of HBV antigens. The findings suggest this drug to be a good antiviral therapeutic candidate for the treatment of HBV infection.

关键词： HBV Oxymatrine CD4+ T cell IFN-γ Mouse

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Multiple-statistical genome-wide association analysis and genomic prediction of fruit aroma and agronomic traits in peaches

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Horticulture Research 2023年第7期10卷 309-320页

作者： Xiongwei Li jiabo wang Mingshen Su Minghao Zhang Yang Hu Jihong Du Huijuan Zhou Xiaofeng Yang Xianan Zhang Huijuan Jia Zhongshan Gao Zhengwen Ye Peach Research Department of Forest&Fruit Tree Institute Shanghai Academy of Agricultural SciencesShanghai 201403China Key Laboratory of Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization(Southwest Minzu University Ministry of Education)ChengduSichuan 610041China Peach Group of Shanghai Runzhuang Agricultural Science and Technology Institute Shanghai 201415China Department of Horticulture Key Laboratory for Horticultural Plant GrowthDevelopment and Quality Improvement of State Agriculture MinistryZhejiang UnihversityHangzhou 310058China

‘Chinese Cling’is an important founder in peach breeding history due to the pleasant ***-wide association studies(GWAS)combined with genomic selection are promising tools in fruit tree breeding,as there is a considerable time lapse between crossing and release of a *** this study,242 peaches from Shanghai germplasm were genotyped with 145456 single-nucleotide polymorphisms(SNPs).The six agronomic traits of fruit flesh color,fruit shape,fruit hairiness,flower type,pollen sterility,and soluble solids content,along with 14 key volatile odor compounds(VOCs),were recorded for multiple-statistical *** the reported candidate genes,six novel genes were identified as associated with these ***-nine significant SNPs were associated with eight *** putative candidate genes were confirmed for VOCs by RNA-seq,including three genes in the biosynthesis pathway found to be associated with linalool,soluble solids content,and cis-3-hexenyl ***-trait genomic prediction enhanced the predictive ability forγ-decalactone to 0.7415 compared with the single-trait model value of *** PTS1-SSR marker was designed to predict the linalool content,and the favorable genotype 187/187 was confirmed,mainly existing in the‘Shanghai Shuimi’***,our findings will be helpful in determining peach accessions with the ideal phenotype and show the potential of multiple-trait genomic prediction to improve accuracy for highly correlated genetic *** diagnostic marker will be valuable for the breeder to bridge the gap between quantitative trait loci and marker-assisted selection for developing strong-aroma cultivars.

关键词： breeding cultivar fir

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Immunological synergistic mechanisms of trans-/cis-stilbene glycosides in Heshouwu-related idiosyncratic liver injury

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Science Bulletin 2017年第11期62卷 748-751页

作者： Lanzhi He Ping Yin Yakun Meng Jinfa Tang Tingting He Ming Niu Yuming Guo Yun Zhu Jing Jing Chunyu Li Zhijie Ma jiabo wang Zhaofang Bai Xiaohe Xiao China Military Institute of Chinese Medicine 302 Military Hospital Beijing 100039 China School of Pharmacy Hunan University of Traditional Chinese Medicine Changsha 410208 China Integrative Medical Center 302 Military Hospital Beijing 100039 China

Heshouwu is a traditional non-toxic Chinese medicine commonly used in the clinical setting;however,clinical cases of Heshouwu-induced hepatotoxicity have been frequently reported^([1]).Pharmacoepidemiological studies have found that Heshouwu-induced liver injury occurs only in a small fraction of individuals taking the drug;these patients presented with the typ-

关键词：肝损伤二苯乙烯苷增效机制异性反式免疫临床病例毒性剂量

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MSRA-Fed:A Communication-Efficient Federated Learning Method Based on Model Split and Representation Aggregate

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ZTE Communications 2022年第3期20卷 35-42页

作者： LIU Qinbo JIN Zhihao wang jiabo LIU Yang LUO Wenjian School of Computer Science and Technology Harbin Institute of TechnologyShenzhen 518055China Guangdong Provincial Key Laboratory of Novel Security Intelligence Technologies Shenzhen 518055China Peng Cheng Laboratory Shenzhen 518055China

Recent years have witnessed a spurt of progress in federated learning,which can coordinate multi-participation model training while protecting the data privacy of ***,low communication efficiency is a bottleneck when deploying federated learning to edge computing and IoT devices due to the need to transmit a huge number of parameters during *** this paper,we verify that the outputs of the last hidden layer can record the characteristics of training ***,we propose a communication-efficient strategy based on model split and representation ***,we make the client upload the outputs of the last hidden layer instead of all model parameters when participating in the aggregation,and the server distributes gradients according to the global information to revise local *** evidence from experiments verifies that our method can complete training by uploading less than one-tenth of model parameters,while preserving the usability of the model.

关键词： federated learning communication load efficient communication privacy protection

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Guidance for the clinical evaluation of traditional Chinese medicine-induced liver injury Issued by China Food and Drug Administration

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Acta Pharmaceutica Sinica B 2019年第3期9卷 648-658页

作者： Xiaohe Xiao Jianyuan Tang Yimin Mao Xiuhui Li jiabo wang Chenghai Liu Kewei Sun Yong’an Ye Zhengsheng Zou Cheng Peng Ling Yang Yuming Guo Zhaofang Bai Tingting He Jing Jing Fengyi Li Na An China Military Institute of Chinese Medicine Beijing302Hospital of ChinaBeijing100039China Center for Drug Evaluation China Food and Drug AdministrationBeijing100022China Renji Hospital of Shanghai Jiaotong University Shanghai200127China Beijing Youan Hospital of Capital Medical University Beijing100069China Shuguang Hospital of Shanghai University of Traditional Chinese Medicine Shanghai200127China First Affiliated Hospital of Hunan University of Traditional Chinese Medicine Changsha410007China Dongzhimen Hospital of Beijing University of Traditional Chinese Medicine Beijing100700China Center for Non-infectious Liver Diseases Beijing302Hospital of ChinaBeijing100039China College of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu610075China College of Pharmacy Shanghai University of Traditional Chinese MedicineShanghai201203China Center for Infectious Liver Diseases Beijing302Hospital of ChinaBeijing100039China

1. Introduction Drug-induced liver injury (DILI), defined as liver injury caused by a drug and/or its metabolites, is a common clinical adverse drug reaction1–4. This type of injury can cause acute liver failure and ... 详细信息

关键词： TCM PTA Guidance for the clinical evaluation of traditional Chinese medicine-induced liver injury Issued by China Food and Drug Administration China

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Landscape of DILI-related adverse drug reaction in China Mainland

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Acta Pharmaceutica Sinica B 2022年第12期12卷 4424-4431页

作者： jiabo wang Haibo Song Feilin Ge Peng Xiong Jing Jing Tingting He Yuming Guo Zhuo Shi Chao Zhou Zixin Han Yanzhong Han Ming Niu Zhaofang Bai Guangbin Luo Chuanyong Shen Xiaohe Xiao Department of Liver Disease Fifth Medical Center of Chinese PLA General HospitalBeijing 100039China School of Traditional Chinese Medicine Capital Medical UniversityBeijing 100069China National Center for ADR Monitoring Beijing 100022China d Department of Chinese Medicine the First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China School of Medicine Case Western Reserve UniversityClevelandOH 44122USA

Drug-induced liver injury(DILI)is a type of bizarre adverse drug reaction(ADR)damaging liver(L-ADR)which may lead to substantial hospitalizations and *** to the general low incidence,detection of L-ADR remains an unsolved public health ***,we used the data of 6.673 million of ADR reports from January 1st,2012 to December 31st,2016 in China National ADR Monitoring System to establish a new database of L-ADR reports for future *** showed that totally 114,357 ADR reports were retrieved by keywords searching of liver-related injuries from the original heterogeneous *** cleaning and standardizing the data fields by the dictionary of synonyms and English translation,we resulted 94,593 ADR records reported to liver injury and then created a new database ready for computer *** reporting status of L-ADR showed a persistent 1.62-fold change over the past five *** national population-adjusted reporting numbers of L-ADR manifested an upward trend with age increasing and more evident in *** annual reporting rate of L-ADR in age group over 80 years old strikingly exceeded the annual DILI incidence rate in general population,despite known underreporting situation in spontaneous ADR reporting *** percentage of herbal and traditional medicines(H/TM)L-ADR reports in the whole number was 4.5%,while 80.60%of the H/TM reports were new *** was great geographical disparity of reported agents,*** cardiovascular and antineoplastic agents were reported in higher socio-demographic index(SDI)regions and more antimicrobials,especially antitubercular agents,were reported in lower SDI *** conclusion,this study presented a large-scale,unbiased,unified,and computer-minable L-ADR database for further ***-,sex-and SDI-related risks of L-ADR incidence warrant to emphasize the precise pharmacovigilance policies within China or other regions in the world.

关键词： Adverse drug reactions Drug-induced liver injury Spontaneous reporting system Database Socio-demographic index Pharmacoepidemiology Pharmacovigilance Geographical disparity

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H.266/VVC中一种改进的仿射运动估计算法

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计算机工程 2022年第3期48卷 296-301页

作者：王佳波杨静上海海事大学信息与工程学院上海201306

通用视频编码标准H.266/VVC通过引入多种新的编码技术,如仿射运动补偿预测、自适应运动矢量精度、多核变换等,以支持360°视频和HDR视频的编解码,从而为用户提供最优的视频质量,但是在H.266/VVC帧间预测过程中,仿射运动估计计算复杂度... 详细信息

通用视频编码标准H.266/VVC通过引入多种新的编码技术,如仿射运动补偿预测、自适应运动矢量精度、多核变换等,以支持360°视频和HDR视频的编解码,从而为用户提供最优的视频质量,但是在H.266/VVC帧间预测过程中,仿射运动估计计算复杂度高导致编码时间显著增加。针对该问题,提出一种改进的仿射运动估计算法。通过对仿射高级矢量预测(AAMVP)候选列表的构建过程进行改进,并构建一种AAMVP候选列表候选项筛选准则,使得列表的候选项更接近编码块真实的运动矢量,从而缩短编码时间。同时对仿射运动估计中迭代搜索最优仿射运动矢量的迭代过程进行优化,以加快迭代搜索速度。实验结果表明,在低时延的编码器配置下,相比VVC原始算法,当BD-BR增加了0.023%时,该算法的总体编码时间平均缩短13%,在保证编码质量的前提下能够有效降低编码的计算复杂度。

关键词： H.266/VVC标准帧间预测仿射运动估计仿射高级运动矢量预测

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