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| 1 | 连续肾替代治疗加用不同剂量血必净对脓毒症合并急性肾损伤患者的影响显示文摘目的:观察连续肾替代治疗(CRRT)加用不同剂量血必净对脓毒症合并急性肾损伤(AKI)患者的影响及安全性。方法:选取2012年6月-2015年8月我院ICU的脓毒症合并AKI患者104例。按照随机数字表法将其分为小、中、大剂量组和对照组,各26例。4组患者均给予基础治疗;小剂量组患者给予血必净注射液50 m L加入0.9%氯化钠注射液(NS)100 m L中,ivgtt,bid;中剂量组患者给予血必净注射液100 m L加入NS 100 m L中,ivgtt,bid;大剂量组患者给予血必净注射液100 m L加入NS 100 m L中,ivgtt,qid。4组患者均治疗1周。观察4组患者治疗前后血清白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、和超敏C反应蛋白(hs-CRP)等炎症因子水平,血尿素氮(BUN)、血肌酐(SCr)和胱抑素(Cys C)等肾功能指标水平,凝血酶原时间(PT)、部分活化凝血活酶时间(APTT)和纤维蛋白原(Fib)等凝血功能指标水平,急性生理与慢性健康状况评分系统Ⅱ(APACHEⅡ)、多器官功能障碍评分系统(Marshall)评分,并记录治疗过程中不良反应发生情况。结果:脱落9例后,本研究最终纳入统计的合格病例数95例,小、中、大剂量组和对照组分别为23、24、25、23例。治疗前,4组患者上述指标比较,差异均无统计学意义(P>0.05)。治疗后,4组患者血清IL-6、TNF-α、CRP、PT、APTT水平和APACEⅡ及Marshall评分均明显降低/缩短,血清BUN、SCr、Cys C、Fib水平均明显升高,小、中、大剂量组患者上述指标改善均明显优于对照组,大剂量组明显优于小、中剂量组,差异均有统计学意义(P<0.05)。4组患者不良反应发生率比较,差异无统计学意义(P>0.05)。结论:CRRT加用大剂量血必净可显著抑制脓毒症合并AKI患者的炎症反应,改善肾功能和凝血功能,且不增加不良反应发生风险。 | 姜启栋 张雪梅 伍长学 | 2017 | 中国药房2017，28，8： | 41 |
| 2 | 中药多成分药代动力学研究:思路与方法显示文摘药物在体内产生药效作用有两个前提条件,其一是给药后药物分子能被机体有效利用(即:能够通过体内的生物屏障到达作用靶位,达到并维持起效浓度);其二是药物分子到达作用靶位的化学形式(原型化合物或代谢物)具有与药效关联的生物活性。中药药代动力学是中药药理学的重要分支,它从中药活性成分能否被机体有效利用的角度,研究与中药药效和安全性相关的物质问题。中药化学组成复杂,通常含众多活性成分,许多中药的发展经过'临床→研究→临床'的过程;与此相对应,化药通常为单一成分,其发展一般经过'研究→临床'的过程;这些带来了中药药代动力学研究有别于化药相关研究的特点。中药药代动力学研究常围绕临床有效中药,为揭示中药药效物质基础迈出关键的一步,并通过'选对成分'和'用好成分'为中药疗效的提高创造条件。作者主要基于其研究团队近年来开展的中药多成分药代动力学研究工作,重点介绍开展这类研究的思路和方法。 | 李川 | 2017 | 中国中药杂志2017，42，4： | 38 |
| 3 | 血必净联合利奈唑胺注射液对老年重症肺炎患者血清肺表面活性蛋白、基质金属蛋白酶及其组织抑制剂水平的影响显示文摘目的:探讨血必净联合利奈唑胺注射液治疗老年重症肺炎患者的临床疗效及对患者血清肺表面活性蛋白(Pulmonary surfactant protein,SP)、基质金属蛋白酶(Matrix metalloproteinases,MMPs)及其组织抑制剂(Matrix metalloproteinases tissue inhibitor,TIMPs)水平的影响。方法:选择我院2015年6月~2017年12月收治的101例老年重症肺炎患者,按随机数字表法分为对照组(n=48)和研究组(n=53)。对照组采用利奈唑胺注射液治疗,研究组在对照组基础上采用血必净治疗。比较两组临床疗效,细菌清除情况,症状缓解时间,治疗前后血清SP、MMPs、TIMPs水平的变化,动脉血气,肺功能,不良反应的发生情况和28天内病死率。结果:治疗后,研究组有效率、细菌清除率均显著高于对照组(均P<0.05),发热消失、血常规恢复、痰液颜色改变及胸部影像明显吸收时间均明显短于对照组(P<0.05);两组血清SP-A、SP-B、SP-C、SP-D、MMP-2、MMP-9及TIMP-1及TIMP-2、血氧饱和度(blood oxygen saturation,SaO_2)、动脉血二氧化碳分压(arterial blood,PaCO_2)、动脉血二氧化碳分压(arterial blood CO_2 partial pressure of CO_2 partial pressure,PaCO_2)、峰流速(peak velocity of flow,PEF)水平均较治疗前显著下降,而血氧饱和度(blood oxygen saturation,SaO_2)、氧分压(oxygen partial pressure,PaO2)、最大呼气中段流量(maximum tidal midexpiratory flow,MMF)、用力肺活量(forced vital capacity,FVC)均较治疗前明显上升,且研究组以上指标变化较对照组更明显(均P<0.05)。两组不良反应的发生情况比较差异无统计学意义(P>0.05),而研究组在28天内病死率显著低于对照组(P<0.05)。结论:血必净联合利奈唑胺注射液对老年重症肺炎患者的疗效优于单用利奈唑胺注射液治疗,可能与其显著降低患者血清SP、MMPs及TIMPs水平,改善肺功能,降低病死率有关。 | 李晓娟 周亮 金丽娟 朱瑞 田娟 | 2018 | 现代生物医学进展2018，18，24： | 22 |
| 4 | 基于网络药理学探讨血必净注射液治疗新型冠状病毒肺炎机制显示文摘目的采用网络药理学方法分析血必净注射液体内活性成分治疗新型冠状病毒肺炎(COVID-19)的潜在作用机制,为临床治疗提供理论依据。方法通过检索文献获取血必净注射液体内活性成,采用TCMSP、PubChem、TargetNet和SEA数据库预测活性成分对应的作用靶点。在Genecards数据库中以'novel coronavirus pneumonia'为关键词搜索COVID-19相关靶点,与血必净注射液靶点映射筛选出共同靶点作为研究靶点,采用Cytoscape 3.2.1软件构建中药-成分-靶点-疾病网络图;将共同靶点导入STRING数据库中构建蛋白质-蛋白质相互作用网络图。结合上述两个网络图筛选出血必净注射液的核心靶点。通过Cytoscape 3.2.1的插件'ClueGO 2.5.5'进行GO生物学过程和KEGG信号通路富集分析。结果槲皮素、没食子酸、木犀草素、迷迭香酸、芦丁、山萘酚、绿原酸、丹参酮IIa、羟基红花黄色素A和芍药苷是血必净注射液发挥治疗作用的主要成分,其作用机制可能与PTGS2、PTGS1、CASP3、RELA、TNF、MAPK1、IL2、IL6和IL10等靶点有关。GO富集分析得出与血必净注射液治疗作用有关的生物过程91个。KEGG富集分析得到与血必净注射液治疗作用相关的信号通路110条。结论血必净注射液具有多成分、多靶标和多通路的特点,可进一步为其治疗(COVID-19)提供重要的理论依据。 | 孔艺 林莉莉 陈永 赖莎 吴红卫 陈吉生 | 2020 | 世界科学技术-中医药现代化2020，22，3： | 16 |
| 5 | LC-MS/MS测定血必净注射液中9种有效成分在大鼠体内血药浓度及药代动力学研究显示文摘该文建立血浆中同时测定血必净注射液9种有效成分含量的高效液相色谱-串联质谱(HPLC-MS/MS)法,并应用于大鼠体内的药动学研究。血浆样品经沉淀蛋白法处理后,待测物和内标以0.1%甲酸水溶液-乙腈进行梯度洗脱,经Waters CORTECS C18色谱柱分离,采用电喷雾电离(ESI)源以多反应监测(MRM)方式进行负离子检测,使用DAS 2.0软件的非房室模型计算药动学参数。大鼠静注6 m L·kg-1血必净注射液后9种有效成分的药动学参数如下:阿魏酸、苯甲酰芍药苷、丹参素、绿原酸、迷迭香酸、羟基红花黄色素A、芍药苷、芍药内酯苷和氧化芍药苷Cmax分别为(85.01±22.33),(56.78±22.78),(36.05±8.77),(73.73±20.26),(173.19±67.12),(20 646.96±2 666.65),(21 416.61±6 427.14),(181.88±38.38),(770.73±230.87)μg·L-1;AUC(0-t n)分别为(801.9±112.3),(1 005.6±406.0),(714.9±237.7),(1 496.3±413.9),(2 316.1±372.2),(1 207 295.3±248 582.6),(788 781.0±308 551.0),(4 785.4±1 076.0),(33 456.2±11 946.1)min·μg·L-1。该方法灵敏、准确,可用于血必净注射液的多成分药动学研究,为血必净注射液临床研究提供基础。 | 欧阳慧子 何俊 | 2018 | 中国中药杂志2018，43，17： | 12 |
| 6 | High degree of pharmacokinetic compatibility exists between the five-herb medicine XueBiJing and antibiotics comedicated in sepsis care显示文摘Managing the dysregulated host response to infection remains a major challenge in sepsis care. Chinese treatment guideline recommends adding Xue Bi Jing, a five-herb medicine, to antibioticbased sepsis care. Although adding Xue Bi Jing further reduced 28-day mortality via modulating the host response, pharmacokinetic herbedrug interaction is a widely recognized issue that needs to be studied.Building on our earlier systematic chemical and human pharmacokinetic investigations of Xue Bi Jing, we evaluated the degree of pharmacokinetic compatibility for Xue Bi Jing/antibiotic combination based on mechanistic evidence of interaction risk. Considering both Xue Bi Jing-antibiotic and antibiotic-Xue Bi Jing interaction potential, we integrated informatics-based approach with experimental approach and developed a compound pair-based method for data processing. To reflect clinical reality, we selected for study Xue Bi Jing compounds bioavailable for drug interactions and 45 antibiotics commonly used in sepsis care in China. Based on the data of interacting with drug metabolizing enzymes and transporters, no Xue Bi Jing compound could pair, as perpetrator, with the antibiotics. Although some antibiotics could,due to their inhibition of uridine 50-diphosphoglucuronosyltransferase 2 B15, organic anion transporters1/2 and/or organic anion-transporting polypeptide 1 B3, pair with senkyunolide I, tanshinol and salvianolic acid B, the potential interactions(resulting in increased exposure) are likely desirable due to these Xue Bi Jing compounds’ low baseline exposure levels. Inhibition of aldehyde dehydrogenase by 7 antibiotics probably results in undesirable reduction of exposure to protocatechuic acid from Xue Bi Jing.Collectively, Xue Bi Jing/antibiotic combination exhibited a high degree of pharmacokinetic compatibility at clinically relevant doses. The methodology developed can be applied to investigate other drug combinations. | Jian Li Olajide E.Olaleye Xuan Yu Weiwei Jia Junling Yang Chuang Lu Songqiao Liu Jingjing Yu Xiaona Duan Yaya Wanga Kai Dong Rongrong He Chen Cheng Chuan Li | 2019 | Acta Pharmaceutica Sinica B2019，9，5： | 10 |
| 7 | 血必净注射液联合抗生素治疗脓毒症:两类药物间高水平药代和谐显示文摘联合用药既需要药物间药效协同互补,也需要药物间能够“药代和谐”(pharmacokinetic compatibility,PKC;不发生会影响药物有效性或安全性的药代性质药物相互作用)。当今世界天然产物制品与化药一同使用既大量存在,又充满争议。一方面,服用葡萄柚汁、圣约翰草制剂等能严重干扰同时进行的化药治疗,这使人们对天然产物制品与化药合用充满戒心;另一方面,越来越多严格的临床和基础研究证明,中药联合化药能更好地应对多因素疾病。脓毒症是一种由感染引起机体反应失调所导致危及生命的器官功能障碍,死亡率高、预后不良。 | 李坚 Olajide EOlaleye 余玄 贾伟伟 杨军令 吕闯 刘松桥 于晶晶 段小娜 王亚亚 董凯 贺容容 程晨 李川 | 2020 | 中国临床药理学与治疗学2020，25，4： | 7 |
| 8 | 中药多成分药代动力学:发现与中药安全性和有效性关联的物质并揭示其药代特征显示文摘中医药对中华民族健康和国家稳定发挥了重要作用,揭示决定中药有效性和安全性的物质是推进中药现代化的一项重要工作。对于化学组成复杂的中药,可通过开展多成分药代研究,根据给药后中药成分能否以某种形式被机体利用产生显著的体内暴露(以成分原形和/或代谢物形式),选拔出用于考察药效活性的中药物质,研究物质产生疗效的体内过程和药代特征,由此为揭示决定中药药效作用的物质创造条件。此外,这类多成分药代研究还可用于揭示与中药不良反应或联合用药风险关联的中药物质。经过十多年的努力,中药多成分药代研究在理论、方法、技术、应用上已取得突破,成为药代动力学的一个新分支。本文系统阐述了中药多成分药代动力学的研究方法、技术要求和分析技术,并用一类活性中药成分(三七的皂苷类成分)的研究和围绕一种已上市中药制剂(连花清瘟胶囊)的研究介绍了两类多成分药代研究实例,最后讨论了中药多成分药代研究的进一步发展。 | 李川 程晨 贾伟伟 杨军令 余玄 Olajide E.OLALEYE | 2021 | 药学学报2021，56，9： | 7 |
| 9 | 近十年中药注射剂药代动力学研究进展显示文摘中药注射剂疗效确切、临床应用广泛,但是其安全性问题也日益受到关注。中药药代动力学对指导中药注射剂给药方案设计、提高临床用药的安全性和有效性具有重要意义。近年来,随着中药研究思路、技术和方法的进步,研究者对中药注射剂开展了广泛而深入的药代动力学研究,取得了显著的进展。该文对近十年来中药注射剂药代动力学研究进行综述,主要从基于分析技术的临床前体内经时过程、分布、代谢和排泄研究、中药注射剂组分相互作用、疾病状态的影响、中药注射剂与化药相互作用以及中药注射剂临床药代动力学研究这几个方面进行归纳总结,以期为中药注射剂的质量控制、产品开发及临床合理应用等相关研究提供参考。 | 刘远荣 詹淑玉 郑博鸿 方梦婷 冯一涵 张洁 李明娟 丁宝月 | 2021 | 中国中药杂志2021，46，7： | 6 |
| 10 | Pharmacokinetics-based identification of pseudoaldosterogenic compounds originating from Glycyrrhiza uralensis roots(Gancao)after dosing LianhuaQingwen capsule显示文摘LianhuaQingwen capsule,prepared from an herbal combination,is officially recommended as treatment for COVID-19 in China.Of the serial pharmacokinetic investigations we designed to facilitate identifying LianhuaQingwen compounds that are likely to be therapeutically important,the current investigation focused on the component Glycyrrhiza uralensis roots(Gancao).Besides its function in COVID-19 treatment,Gancao is able to induce pseudoaldosteronism by inhibiting renal 11β-HSD2.Systemic and colon-luminal exposure to Gancao compounds were characterized in volunteers receiving LianhuaQingwen and by in vitro metabolism studies.Access of Gancao compounds to 11β-HSD2 was characterized using human/rat,in vitro transport,and plasma protein binding studies,while 11β-HSD2 inhibition was assessed using human kidney microsomes.LianhuaQingwen contained a total of 41 Gancao constituents(0.01-8.56μmol/day).Although glycyrrhizin(1),licorice saponin G2(2),and liquiritin/liquiritin apioside(21/22)were the major Gancao constituents in LianhuaQingwen,their poor intestinal absorption and access to colonic microbiota resulted in significant levels of their respective deglycosylated metabolites glycyrrhetic acid(8),24-hydroxyglycyrrhetic acid(M2_(D);a new Gancao metabolite),and liquiritigenin(27)in human plasma and feces after dosing.These circulating metabolites were glucuronized/sulfated in the liver and then excreted into bile.Hepatic oxidation of 8 also yielded M2_(D).Circulating 8 and M2D,having good membrane permeability,could access(via passive tubular reabsorption)and inhibit renal 11β-HSD2.Collectively,1 and 2 were metabolically activated to the pseudoaldosterogenic compounds 8 and M2_(D).This investigation,together with such investigations of other components,has implications for precisely defining therapeutic benefit of LianhuaQingwen and conditions for its safe use. | Xiao-fang Lan Olajide EOlaleye Jun-lan Lu Wei Yang Fei-fei Du Jun-ling Yang Chen Cheng Yan-hong Shi Feng-qing Wang Xue-shan Zeng Nan-nan Tian Pei-wei Liao Xuan Yu Fang Xu Ying-fei Li Hong-tao Wang Nai-xia Zhang Wei-wei Jia Chuan Li | 2021 | Acta Pharmacologica Sinica2021，42，12： | 6 |
| 11 | 基于“五原则”的血必净注射液质量标志物的预测分析显示文摘[目的]基于中药质量标志物(Q-marker)“五原则”——传递与溯源、特有性、有效性、复方配伍环境及可测性,对血必净注射液的Q-marker进行研究。[方法]通过中国知网(CNKI)、万方、Pumbed、Medline等数据库,检索血必净注射液的化学成分、药代动力学、药理作用、临床应用以及质量控制等相关文献,并在此基础上,基于Q-marker的“五原则”,预测分析血必净注射液的Q-marker。[结果]羟基红花黄色素A、丹酚酸B、芍药苷、洋川芎内酯I、洋川芎内酯H可作为血必净注射液的Q-marker。[结论]研究预测了血必净注射液的Q-marker,为后续临床及质量控制研究提供参考依据。 | 蔡楠 曹宁宁 赵利斌 裴帅 李晓璇 张琬靖 肖学凤 刘昌孝 | 2021 | 天津中医药2021，38，8： | 4 |
| 12 | Pretreatment with broad-spectrum antibiotics alters the pharmacokinetics of major constituents of Shaoyao-Gancao decoction in rats after oral administration显示文摘The influence of broad-spectrum antibiotics on the pharmacokinetics and biotransformation of major constituents of Shaoyao-Gancao decoction (SGD) in rats was investigated. The pharmacokinetic behaviors of paeoniflorin (PF), albiflorin (AF), liquiritin (LT), isoliquiritin (ILT), liquiritin apioside (LA), isoliquiritin apioside (ILA), and glycyrrhizic acid (GL), seven major constituents of SGD, as well as glycyrrhetinic acid (GA), a major metabolite of GL, were analyzed. A 1-week pretreatment with broad-spectrum antibiotics (ampicillin, metronidazole, neomycin, 1gL^-1;and vancomycin, 0.5gL^-1) via drinking water reduced plasma exposure of the major constituents. The AUC0-24 h of PF and LT was significantly decreased by 28.7% and 33.8% (P<0.05 and P<0.005), respectively. Although the differences were not statistically significant, the AUC0-24 h of AF, ILT, LA, ILA, and GL was decreased by 31.4%, 50.9%, 16.9%, 44.1%, and 37.0%, respectively, compared with the control group. In addition, the plasma GA exposure in the antibiotic-pretreated group was significantly lower (P<0.005) than the control group. The in vitro stability of the major constituents of SGD in the rat intestinal contents with or without broad-spectrum antibiotics was also investigated. The major constituents were comparatively stable in the rat duodenum contents, and the biotransformation of GL mainly occurred in the rat colon contents. In summary, broad-spectrum antibiotics suppressed the absorption of the major constituents of SGD and significantly inhibited the biotransformation of GL to GA by suppressing the colon microbiota. The results indicated a potential clinical drug–drug interaction (DDI) when SGD was administered with broad-spectrum antibiotics. | Meng Liu Jie Yuan Wen-juan Hu Chang-qiang Ke Yi-fan Zhang Yang Ye Da-fang Zhong Guang-rong Zhao Sheng Yao Jia Liu | 2019 | Acta Pharmacologica Sinica2019，40，2： | 3 |
| 13 | Xuebijing Injection Ameliorates H_(2)S-Induced Acute Respiratory Distress Syndrome by Promoting Claudin-5 Expression显示文摘Objective:To investigate the protective effects and underlying mechanisms of Xuebijing Injection(XBJ)on the lung endothelial barrier in hydrogen sulfide(H2S)-induced acute respiratory distress syndrome(ARDS).Methods:Sprague-Dawley rats were exposed to H2S(300 ppm)to establish ARDS model,while human pulmonary microvascular endothelial cells(HPMECs)were incubated with NaHS(a H2S donor,500μmol/L)to establish cell model.H2S and XBJ were concurrently administered to the rat and cell models.Lung hematoxylin and eosin staining,immunohistochemistry,transmission electron microscopy and wet/dry ratio measurement were used to confirm ARDS induced by H2S in vivo.The expression levels of claudin-5,phosphorylated protein kinase B(p-AKT)/t-AKT and p-forkhead box transcription factor O1(FoxO1)/t-FoxO1 in vivo and in vitro were also assessed.Paracellular permeability and transepithelial electrical resistance(TEER)were measured to evaluate endothelial barrier function in the cell model.Results:The morphological investigation showed that XBJ attenuated H2S-induced ARDS in rats.XBJ significantly ameliorated both the reduction in TEER and the increased paracellular permeability observed in NaHS-treated HPMECs(P<0.05).The protective effects of XBJ were blocked by LY294002,a phosphatidylinositol 3-kinase(PI3K)/AKT/FoxO1 pathway antagonist(P<0.05).Furthermore,XBJ promoted the expression of claudin-5 and increased the levels of p-AKT and p-FoxO1 in vivo and in vitro(P<0.05).Conclusion:XBJ ameliorated H2S-induced ARDS by promoting claudin-5 expression via the PI3K/AKT/FoxO1 signaling pathway. | GENG Ping LING Bing-yu ZHANG Hong-liang XIONG Jia-li WANG Ying YU Fen TAN Ding-yu XU Ji-yang WANG Hui-hui | 2022 | Chinese Journal of Integrative Medicine2022，28，2： | 0 |
| 14 | Research hotspot and frontier progress of cancer under the background of precision medicine显示文摘The timely introduction and rapid development of precision medicine have provided strong theoretical support and technical support for tumor research.The treatment methods have been developed from single to multiple;the research technology has been transformed from macro to micro;the treatment drugs have been updated from systemic chemotherapy to targeted therapy and immunotherapy,and cancer has changed from a highly lethal disease to a'chronic disease'.Based on the current international cancer research hotspots and treatment frontiers,this paper takes stock from five aspects,namely,treatment methods,detection technology,new drug research and development,information data and traditional Chinese medicine,with a view to'from the point to the surface','from the outside to the inside',and'the combination of Chinese and western',so as to explore the overall picture of cancer treatment and research. | Li-Hong Zhou Yan Li Qi Li | 2020 | Traditional Medicine Research2020，5，1： | 0 |
| 15 | Novel assays for quality evaluation of XueBiJing:Quality variability of a Chinese herbal injection for sepsis management显示文摘XueBiJing is an intravenous five-herb injection used to treat sepsis in China.The study aimed to develop a liquid chromatography-tandem mass spectrometry(LC-MS/MS)-or liquid chromatography-ultraviolet(LC-UV)-based assay for quality evaluation of XueBiJing.Assay development involved identifying marker constituents to make the assay therapeutically relevant and building a reliable one-point calibrator for monitoring the various analytes in parallel.Nine marker constituents from the five herbs were selected based on XueBiJing's chemical composition,pharmacokinetics,and pharmacodynamics.A selectivity test(for“similarity of response”)was developed to identify and minimize interference by nontarget constituents.Then,an intercept test was developed to fulfill“linearity through zero”for each analyte(absolute ratio of intercept to C response,<2%).Using the newly developed assays,we analyzed samples from 33 batches of XueBiJing,manufactured over three years,and found small batch-to-batch variability in contents of the marker constituents(4.1%-14.8%),except for senkyunolide I(26.5%). | Xuan Yu Wei Niu Ya-Ya Wang Olajide E.Olaleye Jia-Nan Wang Meng-Yuan Duan Jun-Ling Yang Rong-Rong He Zi-Xuan Chu Kai Dong Gui-Ping Zhang Chang-Xiao Liu Chen Cheng Chuan Li | 2022 | Journal of Pharmaceutical Analysis2022，12，4： | 0 |
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