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| 1 | Evidence chain-based causality identification in herb-induced liver injury: exemplification of a well-known liver-restorative herb Polygonum multiflorum显示文摘草药的药最近在美国作为导致药的肝损害(DILI ) 的第二个很普通的原因被认出了。然而,识别一些植物的 DILI 诱发性的可靠方法例如 Heshouwu (蓼 multiflorum 的弄干的根) ,留下缺乏。在这研究,有肝机能障碍和 Heshouwu DILI 的 147 个报导文学的案例的 12 307 个住院病人的一个总数被屏蔽。一个一般算法仅仅显示了那 22.5%(9/40 ) 并且(45/147 ) 分别地, 30.6% 所有住院和文学案例报告表明 Heshouwu 的 DILI 诱发性的高概率。由对比,(19/20 )95% 生药学,植物化学,和 metabolomic 有希望地调查的所有情况测试展出高度可能的诱发性,包括不正确地以前被归因的一个病人和从由 pharmacognostic 证据的 Heshouwu 诱发性被排除的一个案例。污染也是的毒素(重金属,杀虫剂,和 mycotoxins ) 从 Heshouwu DILI 诱发性排除了。为 Heshouwu DILI 诊断地址安全的这些屏蔽方法的客观性担心考虑包含芪的草药的药和饮食的补充。 | Jiabo Wang Zhijie Ma Ming Niu Yun Zhu Qingsheng Liang Yanling Zhao Jingyuan Song Zhaofang Bai Yaming Zhang Ping Zhang Na Li Yakun Meng Qi Li Lushan Qin Guangju Teng Junling Cao Baosen Li Shilin Chen Yonggang Li Zhengsheng Zou Honghao Zhou Xiaohe Xiao | 2015 | Frontiers of Medicine2015，9，4： | 47 |
| 2 | Screening for main components associated with the idiosyncratic hepatotoxicity of a tonic herb, Polygonum multiflorum显示文摘典型药用的植物的主要成分,蓼 multiflorum (用汉语的 Heshouwu ) ,那导致特质的肝损害仍然保持不清楚。我们的以前的工作证明了有 lipopolysaccharide (LPS ) 的无毒的剂量和 Heshouwu 的治疗学的剂量的 cotreatment 能在老鼠导致肝损害,而独唱治疗不能导致看得见的损害。在现在的工作,用成分大美人和敲门在里面策略,我们发现 Heshouwu 的乙醇醋酸盐(EA ) 摘录在对待 LPS 的老鼠显示了可比较的特质的 hepatotoxicity 到整个摘录。结果显示血浆丙氨酸 aminotransferase, aspartate aminotransferase,和肝 histologic 的重要举起变化,而另外的分开的部分没能导致肝损害。有另外的分开的部分的 EA 摘录的混合在对待 LPS 的老鼠导致了可比较的特质的 hepatotoxicity 到整个摘录。化学分析进一步揭示了那 2,3,5,4-tetrahydroxy trans-stilbene-2-O -- 配糖物(trans-SG ) 和它的 cis 异构体是在 EA 的二主要混合物摘录。而且,孤立的 cis- ,并且不它的 trans 异构体,显示的可比较的特质的 hepatotoxicity 到在对待 LPS 的老鼠的 EA 摘录。cis-SG 的更高的内容从与收集的将军相比与 Heshouwu 联系的实际的肝沉醉病人在 Heshouwu 白酒或准备被检测样品。另外,血浆 metabolomics 分析证明 cis-SG-disturbing 充实显著地不同于的小径在对待 LPS 的老鼠的 trans-SG。所有这些结果建议 cis-SG 仔细与 Heshouwu 的特质的 hepatotoxicity 被联系。认为 trans-SG 的 cis-trans 异构化被紫外光或日光调停,我们的调查结果为在药发现控制 photoisomerization 并且为 Heshouwu 和芪相关的药的临床的使用用作参考。 | Chunyu Li Ming Niu Zhaofang Bai Congen Zhang Yanling Zhao Ruiyu Li Can Tu Huifang Li Jing Jing Yakun Meng Zhijie Ma Wuwen Feng Jinfa Tang Yun Zhu Jinjie Li Xiaoya Shang Zhengsheng Zou Xiaohe Xiao Jiabo Wang | 2017 | Frontiers of Medicine2017，11，2： | 41 |
| 3 | New incompatible pair of TCM:Epimedii Folium combined with Psoraleae Fructus induces idiosyncratic hepatotoxicity under immunological stress conditions显示文摘Epimedii Folium(EF)combined with Psoraleae Fructus(PF)is a common modern preparation,but liver injury caused by Chinese patent medicine preparations containing EF and PF has been frequently reported in recent years.Zhuangguguanjiewan pills(ZGW),which contain EF and PF,could induce immune idiosyncratic liver injury according to clinical case reports and a nonhepatotoxic dose of lipopolysaccharide(LPS)model.This present study evaluated the liver injury induced by EF or PF alone or in combination and investigated the related mechanism by using the LPS model.Liver function indexes and pathological results showed that either EF or PF alone or in combination led to liver injury in normal rats;however,EF or PF alone could lead to liver injury in LPS-treated rats.Moreover,EF combined with PF could induce a greater degree of injury than that caused by EF or PF alone in LPS-treated rats.Furthermore,EF or PF alone or in combination enhanced the LPS-stimulated inflammatory cytokine production,implying that IL-1β,which is processed and released by activating the NLRP3 inflammasome,is a specific indicator of EF-induced immune idiosyncratic hepatotoxicity.Thus,EF may induce liver injury through enhancing the LPS-mediated proinflammatory cytokine production and activating the NLRP3 inflammasome.In addition,the metabolomics analysis results showed that PF affected more metabolites in glycerophospholipid and sphingolipid metabolic pathways compared with EF in LPS model,suggesting that PF increased the responsiveness of the liver to LPS or other inflammatory mediators via modulation of multiple metabolic pathways.Therefore,EF and PF combination indicates traditional Chinese medicine incompatibility,considering that it induces idiosyncratic hepatotoxicity under immunological stress conditions. | Yuan Gao Zhilei Wang Jinfa Tang Xiaoyi Liu Wei Shi Nan Qin Xiaoyan Wang Yu Pang Ruisheng Li Yaming Zhang Jiabo Wang Ming Niu Zhaofang Bai Xiaohe Xiao | 2020 | Frontiers of Medicine2020，14，1： | 32 |
| 4 | Immunological synergistic mechanisms of trans-/cis-stilbene glycosides in Heshouwu-related idiosyncratic liver injury显示文摘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- | 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 | 2017 | Science Bulletin2017，62，11： | 29 |
| 5 | Guidance for the clinical evaluation of traditional Chinese medicine-induced liver injury Issued by China Food and Drug Administration显示文摘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 even death in severe cases5. | 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 | 2019 | Acta Pharmaceutica Sinica B2019，9，3： | 22 |
| 6 | T cell–associated immunoregulation and antiviral effect of oxymatrine in hydrodynamic injection HBV mouse model显示文摘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.The 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. | 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 | 2017 | Acta Pharmaceutica Sinica B2017，7，3： | 20 |
| 7 | Cardamonin from a medicinal herb protects against LPS-induced septic shock by suppressing NLRP3 inflammasome显示文摘Aberrant activation of NLRP3 inflammasome has been implicated in the pathogenesis of diverse inflammation-related diseases, and pharmacological molecules targeting NLRP3 inflammasome are of considerable value to identifying potential therapeutic interventions. Cardamonin(CDN), the major active ingredient of the traditional Chinese medicinal herb Alpinia katsumadai, has exerted an excellent anti-inflammatory activity, but the mechanism underlying this role is not fully understood. Here, we show that CDN blocks canonical and noncanonical NLRP3 inflammasome activation triggered by multiple stimuli. Moreover, the suppression of CDN on inflammasome activation is specific to NLRP3, not to NLRC4 or AIM2 inflammasome. Besides, the inhibitory effect is not dependent on the expression of NF-κB-mediated inflammasome precursor proteins. We also demonstrate that CDN suppresses the NLRP3 inflammasome through blocking ASC oligomerization and speckle formation in a dose-dependent manner.Importantly, CDN improves the survival of mice suffering from lethal septic shock and attenuates IL-1βproduction induced by LPS in vivo, which is shown to be NLRP3 dependent. In conclusion, our results identify CDN as a broad-spectrum and specific inhibitor of NLRP3 inflammasome and a candidate therapeutic drug for treating NLRP3 inflammasome-driven diseases. | Zhilei Wang Guang Xu Yuan Gao Xiaoyan Zhan Nan Qin Shubin Fu Ruisheng Li Ming Niu Jiabo Wang Youping Liu Xiaohe Xiao Zhaofang Bai | 2019 | Acta Pharmaceutica Sinica B2019，9，4： | 19 |
| 8 | Landscape of DILI-related adverse drug reaction in China Mainland显示文摘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 mortality.Due to the general low incidence,detection of L-ADR remains an unsolved public health challenge.Therefore,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 investigation.Results showed that totally 114,357 ADR reports were retrieved by keywords searching of liver-related injuries from the original heterogeneous system.By 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 mining.The reporting status of L-ADR showed a persistent 1.62-fold change over the past five years.The national population-adjusted reporting numbers of L-ADR manifested an upward trend with age increasing and more evident in men.The 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 system.The 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 findings.There was great geographical disparity of reported agents,i.e.more cardiovascular and antineoplastic agents were reported in higher socio-demographic index(SDI)regions and more antimicrobials,especially antitubercular agents,were reported in lower SDI regions.In conclusion,this study presented a large-scale,unbiased,unified,and computer-minable L-ADR database for further investigation.Age-,sex-and SDI-related risks of L-ADR incidence warrant to emphasize the precise pharmacovigilance policies within China or other regions in the world. | 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 | 2022 | Acta Pharmaceutica Sinica B2022，12，12： | 12 |
| 9 | Bavachin enhances NLRP3 inflammasome activation induced by ATP or nigericin and causes idiosyncratic hepatotoxicity显示文摘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 settings.However,liver injury caused by PF and its preparations has been frequently reported in recent years.Our previous studies have demonstrated that PF could cause idiosyncratic drug-induced liver injury(IDILI),but the mechanism underlying its hepatotoxicity remains unclear.This paper reports that bavachin isolated from PF enhances the specific stimuli-induced activation of the NLRP3 inflammasome and leads to hepatotoxicity.Bavachin 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 lipopolysaccharide.Bavachin does not affect AIM2 or NLRC4 inflammasome activation.Mechanistically,bavachin specifically increases the production of nigericin-induced mitochondrial reactive oxygen species among the most important upstream events in the activation of the NLRP3 inflammasome.Bavachin 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 IDILI.These results suggest that bavachin specifically enhances the ATP-or nigericin-induced activation of the NLRP3 inflammasome.Bavachin also potentially contributes to PF-induced idiosyncratic hepatotoxicity.Moreover,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. | 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 | 2021 | Frontiers of Medicine2021，15，4： | 9 |
| 10 | Clinical characteristics of 96 patients with drug-induced acute liver failure:a comparison between Traditional Chinese and Western Medicine显示文摘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 examined.RESULTS: 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. | 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 | 2017 | Journal of Traditional Chinese Medicine2017，37，3： | 3 |
| 11 | Asari Radix et Rhizoma consumption lacks relevance for hepatocellular carcinoma in patients:A retrospective cohort study显示文摘Objective:Although some studies have linked Asari Radix et Rhizoma(Asari Radix)administration to hepatocellular carcinoma(HCC),few studies have examined the association between the development of HCC and use of Asari Radix among patients in China's Mainland.This study aimed to evaluate the realworld association between Asari Radix and HCC in patients to strengthen the understanding of Asari Radix safety.Methods:A retrospective cohort study among hepatitis B virus(HBV)-monoinfected patients and nonHBV-monoinfected patients were performed.Patients over 18 years of age were eligible for inclusion.Prescription records of inpatients and outpatients were inquired to distinguish Asari Radix users and nonusers.The risk of developing HCC among Asari Radix users and nonusers in the HBV cohort and the non-HBV cohort was analyzed.Results:There were 49500 HBV and 133148 non-HBV patients involved in the two cohorts.Among HBV patients(2901 users;46599 nonusers),the prevalence of HCC in Asari Radix users was lower than that in nonusers(145.70 vs.265.43 per 105).Among non-HBV patients(5042 users;128106 nonusers),the prevalence of HCC in Asari Radix users was lower than that in nonusers(81.62 vs.134.11 per 105).None of the hazard ratios(HRs)of Asari Radix exposure ranging from 1 g to 200 g in the two cohorts showed correlation between Asari Radix exposure and hepatocarcinogenesis.Conclusion:An obvious irrelevancy was found between the consumption of Asari Radix and HCC development both in patients with and in those without HBV infection.Use of Asari Radix under 200 g appears safe in terms of HCC risk in the Chinese population;further prospective studies are needed to confirm our results. | Zhi-e Fang Yuming Guo Zhilei Wang Tingting He Jiabo Wang Zhaofang Bai Xiaohe Xiao | 2022 | Chinese Herbal Medicines2022，14，3： | 2 |
| 12 | The structure of nonlinear Lie derivations on yon Neumann algebras显示文摘 | Bai Zhaofang Du Shuanping | 2012 | Linear Algebra and its Applications2012，436，： | 1 |
| 13 | Linear maps and additive maps that preserve operators annihilated by a polynomial显示文摘 | Bai Zhaofang Hou Jinchuan | 2002 | Journal of Mathematical Analysis and Applications2002，271，： | 1 |
| 14 | Multiplicative *-Lie isomorphisms between factors显示文摘 | BAI Zhaofang DU Shuanping | 2008 | Journal of Mathematical Anap- plications2008，346，： | 1 |
| 15 | Multiplieative * -Lie isomorphisms between von Neumann algebras显示文摘 | BAI Zhaofang DU Shuanping | 2012 | Linear and Mul- tilinear Algebra2012，60，3： | 1 |
| 16 | Maps preserving product XY-YX * on von Neumann algebras显示文摘 | BAI Zhaofang DU Shuanping | 2012 | Jornal of Mathematical Analysis and Applications2012，386，： | 1 |
| 17 | Aristolochic acids exposure was not the main cause of liver tumorigenesis in adulthood显示文摘Aristolochic acids(AAs) have long been considered as a potent carcinogen due to its nephrotoxicity. Aristolochic acid I(AAI) reacts with DNA to form covalent aristolactam(AL)-DNA adducts,leading to subsequent A to T transversion mutation, commonly referred as AA mutational signature. Previous research inferred that AAs were widely implicated in liver cancer throughout Asia. In this study, we explored whether AAs exposure was the main cause of liver cancer in the context of HBV infection in China's Mainland. Totally 1256 liver cancer samples were randomly retrieved from 3 medical centers and a refined bioanalytical method was used to detect AAI-DNA adducts. 5.10% of these samples could be identified as AAI positive exposure. Whole genome sequencing suggested 8.41% of 107 liver cancer patients exhibited the dominant AA mutational signature, indicating a relatively low overall AAI exposure rate. In animal models, long-term administration of AAI barely increased liver tumorigenesis in adult mice, opposite from its tumor-inducing role when subjected to infant mice. Furthermore, AAI induced dose-dependent accumulation of AA-DNA adduct in target organs in adult mice, with the most detected in kidney instead of liver. Taken together, our data indicate that AA exposure was not the major threat of liver cancer in adulthood. | Shuzhen Chen Yaping Dong Xinming Qi Qiqi Cao Tao Luo Zhaofang Bai Huisi He Zhecai Fan Lingyan Xu Guozhen Xing Chunyu Wang Zhichao Jin Zhixuan Li Lei Chen Yishan Zhong Jiao Wang Jia Ge Xiaohe Xiao Xiuwu Bian Wen Wen Jin Ren Hongyang Wang | 2022 | Acta Pharmaceutica Sinica B2022，12，5： | 1 |
| 18 | Screening for main components associated with the idiosyncratic hepatotoxicity of a tonic herb,Polygonum multiflorum显示文摘Erratum to Frontiers of Medicine 201711(2):253–265 http://gffzzd3cc09b8251d45dfskf55vcfwfbok6cpp.ffgz.tsg.suse.edu.cn/10.1007/s11684-017-0508-9 The original version of this article unfortunately contained some mistakes.The panel of“LPS–/drug–”in Fig.3B(Page 259),the panels of“LPS–/EtoAc+”and“LPS–/Residue+”in Supplementary Fig.3(Page 7 in the online supplementary materials)should be corrected.The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. | Chunyu Li Ming Niu Zhaofang Bai Congen Zhang Yanling Zhao Ruiyu Li Can Tu Huifang Li Jing Jing Yakun Meng Zhijie Ma Wuwen Feng Jinfa Tang Yun Zhu Jinjie Li Xiaoya Shang Zhengsheng Zou Xiaohe Xiao Jiabo Wang | 2021 | Frontiers of Medicine2021，15，2： | 0 |
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