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Amplifying protection against acute lung injury:Targeting both inflammasome and cGAS-STING pathway by Lonicerae Japonicae Flos-Forsythiae Fructus drug pair

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Chinese Herbal Medicines 2024年第3期16卷 422-434页

作者： Junjie Li Ming Dong Qing Yao Xu Dong Yuanyuan Chen Jincai Wen Yingjie Xu Zhixin Wu Xiaomei Zhao Ye Xiu xiaoyan zhan Zhaofang Bai Xiaohe Xiao Chengde Medical University Chengde 067000China Department of Hepatology The Fifth Medical Center of PLA General HospitalBeijing 100039China China Military Institute of Chinese Materia Fifth Medical Center of Chinese PLA General HospitalBeijing 100039China National Key Laboratory of Kidney Diseases The Fifth Medical Center of PLA General HospitalBeijing 100039China School of Stomatology Heilongjiang Key Lab of Oral Biomedicine Materials and Clinical Application&Experimental Center for Stomatology EngineeringJiamusi UniversityJiamusi 154007China Southern Medical University Guangzhou 510515China

Objective:Acute lung injury(ALI)is characterized by inflammation and currently lacks an efficacious pharmacological *** medicine combination of Lonicerae Japonicae Flos(LJF)and Forsythiae Fructus(FF)demonstrates combined properties in its anti-infective,anti-inflammatory,and therapeutic effects,particularly in alleviating respiratory *** previous studies,Chinese medicine has shown promising efficacy in lipopolysaccharides(LPS)-induced ***,there have been no reports of LJF and FF pairing for lung *** aim of this study is to compare the efficacy of herb pair Lonicerae Japonicae Flos-Forsythiae Fructus(LF)with LJF or FF alone in the treatment of ALI,and to explore whether LJF and FF have a combined effect in the treatment of lung injury,along with the underlying mechanism ***:A total of 36 mice were divided into six groups(control,model,LJF,FF,LF,dexamethasone)based on the treatments they received after undergoing sham-operation/LPS tracheal instillation.H&E staining and pulmonary edema indexes were used to evaluate lung injury *** exudate cells(AECs)were counted based on cell count in bronchoalveolar lavage fluid(BALF),and neutrophil percentage in BALF was measured using flow ***(MPO)activity in BALF was measured using enzyme-linked immunosorbent assay(ELISA),while the production of IL-1β,TNF-α,and IL-6 in the lung and secretion level of them in BALF were detected by quantitative polymerase chain reaction(qPCR)and *** effect of LJF,FF,and LF on the expression of Caspase-1 and IL-1βproteins in bone marrow derived macrophages(BMDMs)supernatant was assessed using Western blot method under various inflammasome activation *** addition,the concentration of IL-1βand changes in lactatedehydrogenase(LDH)release levels in BMDMs supernatant after LJF,FF,and LF administration,respectively,were measured using ***,the effects of LJF,FF and LF on STING and IRF3 phosphor

关键词： acute lung injury BMDMS inflammasomes Lonicerae Japonicae Flos-Forsythia Fructus drug pair STING

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中药安全性评价:新时代,新策略

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Acupuncture and Herbal Medicine 2024年第2期4卷 171-175,I0004页

作者：赵旭柏兆方湛小燕王伽伯郑永齐肖小河中国人民解放军总医院第五医学中心肝病医学部首都医科大学中医药学院耶鲁大学中医药全球化联盟

当今,随着中药在全球范围内使用越来越广泛,中药安全性领域出现了诸多新问题和新挑战,特别是传统“无毒”中药频频曝出肝损伤、肾损害等安全性问题/事件,颠覆了人们对中药毒性与安全性的传统认知,也给中医药健康及国际化带来了巨大挑战... 详细信息

当今,随着中药在全球范围内使用越来越广泛,中药安全性领域出现了诸多新问题和新挑战,特别是传统“无毒”中药频频曝出肝损伤、肾损害等安全性问题/事件,颠覆了人们对中药毒性与安全性的传统认知,也给中医药健康及国际化带来了巨大挑战。那么如何客观认识中药安全性的形势及问题?如何科学破解中药安全性评价与风险防控难题?,本团队提出:一是要与时俱进,辨证看待中药安全性问题和形势,不要夸大,也不要小视;二是要突破“唯药物论毒性”的传统认知,创新中药毒性理论与安全性评价模式;三是要针对不同毒性类型中药,建立安全风险精准防控对策,推动中药安全风险管理从被动应对向科学主动防控转变。在此基础上,提出了“中药新安全观”思想及方法体系,希冀为系统性地破解中药安全性评价与风险防控难题提供新理论、新策略、新方法及成功范例。

关键词：肝毒性中药新安全观风险防控安全性评价中药

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中药安全性评价理论创新与技术突破:病证毒理学

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中国药物警戒 2024年第1期21卷 6-14页

作者：柏兆方湛小燕姚清陈思敏赵旭肖小河解放军总医院第五医学中心全军中医药研究所北京100029 解放军总医院第五医学中心肝病医学部北京100029 南方医科大学中医药学院广东广州510515 安徽医科大学药学院安徽合肥230031

目的提出病证毒理学理论及方法体系,皆在促进病证毒理学在中药新药开发、中药临床安全性评价以及中药安全精准用药对策制定方面的科学、合理和高效运用,促进中医药事业健康可持续发展。方法结合病证毒理学实践运用情况,全面定义病证毒... 详细信息

目的提出病证毒理学理论及方法体系,皆在促进病证毒理学在中药新药开发、中药临床安全性评价以及中药安全精准用药对策制定方面的科学、合理和高效运用,促进中医药事业健康可持续发展。方法结合病证毒理学实践运用情况,全面定义病证毒理学的外延和内涵,并系统梳理基于病证毒理学的中药安全性研究新理论、新方法和新发现。结果中药毒性主要分为固有毒性和特异质毒性2种类型,由于特异质毒性具有偶发性,易感性和难预测等特点,常规毒理学模式和方法难以评价,为此本团队传承创新中医“有故无殒”毒效思想,2016年首次提出病证毒理学理论和方法,皆在突破常规毒理学模式和方法局限性,科学厘清遗传、体质、疾病和证候等机体因素对中药安全性的影响规律和主次关系,解决中药特异质毒性评价难题。近年来,本团队在不断完善和优化病证毒理学理论和方法体系基础上,以临床真实世界和体内外病证易感模型为主要评价模式,开展了何首乌、补骨脂和淫羊藿等中药及及其相关制剂特异质毒性的易感人发现识别、成因机制解析及风险防控对策研究,破解了系列传统“无毒”中药安全性评价及风险防控难题。结论病证毒理学不仅可以用于特异质毒性中药的易感人群识别、成因机制解析以及风险防控对策研究,还可以用于固有毒性中药的“病(证)-量-时-毒-效”关系以及安全治疗窗研究。病证毒理学创新发展了中药毒理学理论和方法,为中药安全精准用药提供了奠基性理论和技术支撑。

关键词：中药安全性病证毒理学毒性理论体系技术创新

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优化氧疗策略在伴低氧血症的急性心肌梗死患者经皮冠状动脉介入治疗后的应用评价

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岭南心血管病杂志 2024年第1期30卷 92-96页

作者：黄嘉熙梁颖聪程贵粉詹晓燕南方医科大学附属广东省人民医院(广东省医学科学院)心内监护室广州510080

目的探讨优化氧化策略在伴低氧血症的急性心肌梗死(acute myocardial infarction,AMI)患者经皮冠状动脉介入(percutaneous coronary intervention,PCI)治疗后的应用效果。方法选取2020年3月至2021年12月在广东省人民医院接受治疗的伴有... 详细信息

目的探讨优化氧化策略在伴低氧血症的急性心肌梗死(acute myocardial infarction,AMI)患者经皮冠状动脉介入(percutaneous coronary intervention,PCI)治疗后的应用效果。方法选取2020年3月至2021年12月在广东省人民医院接受治疗的伴有低氧血症的AMI患者600例。按照入院24 h内最低血氧饱和度(arterial oxygen saturation,SaO2)是否≥95%或吸氧后动脉血气分析氧分压是否≥75 mmHg(1 mmHg=0.133 kPa)分成高血氧目标组(n=200)及低血氧目标组(n=100)。结果高血氧目标组患者的监护室住院时间短于低血氧目标组,差异有统计学意义(t=27.838,P0.05)。高血氧目标组患者的左心室射血分数(left ventricular ejection fraction,LVEF)高于低血氧目标组,差异有统计学意义(t=-6.285,P<0.01)。高血氧目标组患者入院48 h、72 h血清氨基末端脑钠肽前体(N-terminal pro-brain natriuretic peptide,NT-proBNP)、可溶性生长刺激表达基因2蛋白(soluble growth stimulation expressed gene 2,sST2)、肌酸激酶同工酶(creatine kinase isoenzymes,CK-MB)浓度均低于低血氧目标组,差异有统计学意义(P<0.05)。结论优化氧疗策略有助于改善伴低氧血症的AMI患者PCI治疗后的预后。

关键词：心肌梗死优化氧疗策略低氧血症心脏重症监护

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血清维生素B_(12)与老年2型糖尿病轻度认知功能障碍的关系

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临床荟萃 2024年第1期39卷 34-37页

作者：张佳楠孙琳琳詹潇燕李冰锦州医科大学抚顺市中心医院研究生培养基地辽宁抚顺113006 抚顺市中心医院内分泌科辽宁抚顺113006

目的探讨血清维生素B_(12)(VB_(12))水平与老年2型糖尿病(T2DM)合并轻度认知功能障碍(MCI)的相关性。方法收集2023年1月-2023年7月在抚顺市中心医院内分泌科收治入院的老年T2DM患者共120例,根据血清VB_(12)正常水平进行三等分,将患者... 详细信息

目的探讨血清维生素B_(12)(VB_(12))水平与老年2型糖尿病(T2DM)合并轻度认知功能障碍(MCI)的相关性。方法收集2023年1月-2023年7月在抚顺市中心医院内分泌科收治入院的老年T2DM患者共120例,根据血清VB_(12)正常水平进行三等分,将患者分为A组(200≤VB_(12)<500 ng/L)36例,B组(500≤VB_(12)<800 ng/L)71例,C组(800≤VB_(12)<1100 ng/L)13例,采用简易蒙特利尔认知评估(MoCA)量表对各组进行认知功能评定比较。比较3组MCI患病率。用logistic回归分析维生素B_(12)的不同水平与MCI的相对风险。结果 MCI发病率随VB_(12)水平的增高而降低。校正了性别、年龄、TC、HDL-C、LDL-C变量后,logistic回归结果显示,以C组为参照组,A组发生MCI的OR值(95%CI)为6.121(1.161~32.265)。结论 200≤VB_(12)<500 ng/L是老年T2DM患者合并MCI的独立危险因素。

关键词：糖尿病,2型维生素B_(12) 轻度认知功能障碍

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桂枝加龙骨牡蛎汤治疗失眠症的Meta分析

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世界睡眠医学杂志 2024年第1期11卷 47-55页

作者：刘巧云覃雅君廖慧詹笑妍杨志敏徐碧云广州中医药大学第二临床医学院广州510405 广州中医药大学第二附属医院广州510120

目的:系统评价桂枝加龙骨牡蛎汤治疗失眠症的临床有效性和安全性。方法:在国家知识基础设施数据库(CNKI)、中国学术期刊数据库(CSPD)、中文科技期刊数据库(CCD)、中国生物医学文献数据库、Pubmed、Web of Science、Embase等网站检索建库... 详细信息

目的:系统评价桂枝加龙骨牡蛎汤治疗失眠症的临床有效性和安全性。方法:在国家知识基础设施数据库(CNKI)、中国学术期刊数据库(CSPD)、中文科技期刊数据库(CCD)、中国生物医学文献数据库、Pubmed、Web of Science、Embase等网站检索建库至2022年3月28日发表的关于桂枝加龙骨牡蛎汤治疗失眠症的随机对照试验(RCT)文献。由2名研究员进行文献筛选、资料提取、偏倚分析后,运用RevMan5.3软件进行Meta分析。结果:最终纳入RCT文献共17篇,涉及1 395例患者。Meta分析结果显示,桂枝加龙骨牡蛎汤的治疗有效率高于对照组OR(95%CI)为3.93(2.61~5.90),匹兹堡睡眠质量指数量表(PSQI)总分下降高于对照组MD(95%CI)为-2.05(-2.72~-1.38)。结论:桂枝加龙骨牡蛎汤可有效提高失眠症治疗有效率,缓解相关症状。但受纳入研究质量影响,该研究结论还有待高质量临床研究验证。

关键词：失眠症桂枝加龙骨牡蛎汤 Meta分析

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Cardamonin from a medicinal herb protects against LPS-induced septic shock by suppressing NLRP3 inflammasome

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Acta Pharmaceutica Sinica B 2019年第4期9卷 734-744页

作者： Zhilei Wang Guang Xu Yuan Gao xiaoyan zhan Nan Qin Shubin Fu Ruisheng Li 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 School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing 100029China School of Pharmacy Jiangxi University of Traditional Chinese MedicineNanchang 330004China Research Center for Clinical and Translational Medicine the Fifth Medical CentreChinese PLA General HospitalBeijing 100500China Integrative Medical Center the Fifth Medical CentreChinese PLA General HospitalBeijing 100039China

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 ***, 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.

关键词： Cardamonin NLRP3 inflammasome IL-1β Caspase-1 Septic shock

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Study on the Precise Location of the Xinjiang Yutian M_S7.3 Earthquake

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Earthquake Research in China 2015年第1期29卷 57-67页

作者： zhan xiaoyan Song Xiuqing Chen Xiangjun Wang Jun Miao Fajun Liu Shuangqing Zhu Yuanqing Earthquake Administration of Jiangsu Province Earthquake Administration of Shanghai Municipality Earthquake Administration of Xinjiang Uygur Autonomous Region Earthquake Administration of Tianjin Municipality

The seismic waveform of the Yutian Ms7. 3 earthquake, Xinjiang on February 12, 2014 was recorded clearly and completely by the Digital Seismic Networks of Xinjiang, Qinghai, Tibet, and Xinjiang Hotan array, so the method of joint location by regional seismic network and seismic array can be used to accurately determine the earthquake source location. The following technologies were used in the process of location：（ 1 ） We selected seismic stations equally located around the epicenter of the Ms 7. 3 earthquake with an average interval of about 15 degrees in the initial location. （2） The recording waveforms of Yutian seismic station were rotated to the radial and tangential directions to precisely obtain the arrival time of S-waves to determine the epicentral distance. （ 3） The velocity model was used in the determination of location of the epicenter, based on the historical records of earthquakes in the area within a radius of 1.0 ° from the source as the center, and the velocity model is obtained after re-fitting and calibration. （4） Based on the waveform records of the Hotan seismic array, the method of waveform beaming was used to determine the azimuths and perform the correction of the epicenter location with these azimuths. （5） The deterministic method was used to measure the source depth. Finally, it is concluded that the Yutian Ms 7. 3 main shock hypocenter location is 36. 197°N, 82. 467°E, focal depth 12km and original time 17：19：48. 2 μm. February 12, 2014.

关键词： Hypocentral location Digital seismic network Seismic array

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

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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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