Due to the non-specific distribution of drugs in the body and the low concentration at the tumor site in traditional chemotherapy, there are challenges associated with significant side effects and tumor resistance. Therefore, a drug delivery system (DDS) urgently needs to be developed that can precisely target tumors. Metal-organic frameworks (MOFs) possess advantageous characteristics derived from organic and inorganic materials, including small particle size, large specific surface area, high drug loading capacity, adjustable structure and pore size, as well as ease of modification. Consequently, MOFs offer unique advantages for designing active targeting, passive targeting, and stimulus-responsive targeting strategies and have become a hot topic of current research on tumor-targeted drug delivery systems. This review will elaborate on the application of MOFs in tumor-targeted drug delivery systems from the perspective of different targeting strategies. We hope that this paper can provide assistance for tumor-targeted therapy.

This study aims to investigate the mechanism of total saponins of Paridis Rhizoma in inducing the ferroptosis of MCF-7 cells and provide a theoretical basis for the clinical treatment of breast cancer with total saponins of Paridis Rhizoma. The methyl thiazolyl tetrazolium(MTT) assay was employed to examine the effects of different concentrations of total saponins of Paridis Rhizoma on the proliferation of MCF-7 cells. A phase contrast inverted microscope was used to observe the morphological changes of MCF-7 cells. The colony formation assay was employed to test the colony formation of MCF-7 cells. The lactate dehydrogenase(LDH) release test was conducted to determine the cell membrane integrity of MCF-7 cells. The cell scratch assay was employed to examine the migration of MCF-7 cells. After that, the level of reactive oxygen species(ROS) in MCF-7 cells was observed by an inverted fluorescence microscope, and the content of Fe~(2+) in MCF-7 cells was detected by the corresponding kit. Transmission electron microscopy was employed to observe the mitochondrial ultrastructure of MCF-7 cells. Western blot was employed to determine the expression of ferroptosis-related proteins, such as p53, solute carrier family 7 member 11(SLC7A11), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long-chain family member 4(ACSL4), and transferrin receptor protein 1(TFR1) in MCF-7 cells. The results showed that 1.5, 3, 4.5, 6, 7.5, and 9 μg·mL~(-1) total saponins of Paridis Rhizoma significantly inhibited the proliferation of MCF-7 cells, with the IC_(50) of 4.12 μg·mL~(-1). Total saponins of Paridis Rhizoma significantly damaged the morphology of MCF-7 cells, leading to the formation of vacuoles and the gradual shrinkage and detachment of cells. Meanwhile, total saponins of Paridis Rhizoma inhibited the colony formation of MCF-7 cells, destroyed the cell membrane(leading to the release of LDH), and shortened the migration distance of MCF-7 cells. Total saponins of Paridis Rhizoma treatment significantly increased the content of ROS, induced oxidative damage, and led to the accumulation of Fe~(2+) in MCF-7 cells. Furthermore, total saponins of Paridis Rhizoma changed the mitochondrial structure, increased the mitochondrial membrane density, led to the decrease or even disappear of ridges, promoted the expression of p53 protein, down-regulated the expression of SLC7A11 and GPX4, and up-regulated the expression of ACSL4 and TFR1. In summary, total saponins of Paridis Rhizoma can significantly inhibit the proliferation and migration of MCF-7 cells and destroy the cell structure by inducing ferroptosis.

通过分析药事管理学教学"五育"融合现状,结合课程教学目标,明确全方位、全过程教育理念,探求药事管理学"五育"的融合点,分析教学内容、方式与"五育"融合的策略,以培养出德智体美劳全面发展的药事管理专业人才.

古代经典名方,是指至今仍广泛应用、疗效确切、具有明显特色与优势的古代中医典籍所记载的方剂.近年来,我国出台一系列法律法规,积极鼓励开发经典名方.2018年,第一批古代经典名方目录公布,为深入挖掘中医药宝库中的精华开启方便之门.小承气汤出自张仲景《伤寒论》,方由大黄、枳实、厚朴三味药组成,适用于治疗阳明腑实轻证.查阅文献发现,关于小承气汤历史沿革的考证,化学成分、药理研究都已有文献记载,而有关小承气汤临床应用的文献都十分零散.其临床应用所涉及的疾病广泛,但至今未有较为详细的总结.作者将小承气汤的古今文记载、药理作用及其近代临床应用的相关文献进行了整理,并进行归纳.据统计有关"小承气汤临床应用"的文献共有304篇,主要涉及消化系统疾病、术后治疗、呼吸系统疾病及其他.其中治疗消化系统疾病的文献最多,共有151篇,涉及胃部和肠部的共128篇,占总数的42.11％.温故而知新,通过对小承气汤临床应用等信息的统计,以期为其进一步的开发应用提供依据.

目的 通过网络药理学方法对金银花-黄连治疗咽炎的作用机制进行预测,并进行初步动物实验验证.方法 通过TCMSP数据库筛选金银花与黄连的有效成分;输入Pharm Mapper数据库获得相应基因;检索GeneCards数据库获得咽炎的靶点基因;利用R语言3.6.1截取交集网络获得候选靶点;借助Cytoscape 3.7.1将"药物-化合物-靶点-疾病"网络可视化处理;在STRING平台构建PPI网络;利用DAVID数据库对候选靶点进行GO富集分析和KEGG通路注释;使用AutoDock Vina 4.2.6,将关键靶点与关键成分进行分子对接,并使用PyMol进行可视化处理.最后通过急性咽炎大鼠实验模型验证金银花-黄连对两种靶点基质金属蛋白酶2(MMP-2)、白介素2(IL-2)的影响.结果 共获得33个有效化合物,183个不重复的靶标信息,46个疾病治疗靶点;GO与KEGG富集分析分别得到48条目和48条信号通路,主要涉及雌激素信号通路、促性腺激素释放信号通路、Ras信号通路、T细胞受体信号通路.分子对接结果显示金银花-黄连中有效成分黄柏酮、掌叶二蒽酮A与关键靶点MMP-2、表皮生长因子受体(EGFR)、丝裂原活化蛋白激酶1(MAPK1)具有自发亲和力.动物实验证实金银花-黄连高、中、低剂量能降低急性咽炎大鼠血清中的MMP-2、IL-2水平.结论 通过网络药理学和实验验证,初步预测了金银花-黄连治疗咽炎可能的药效物质基础及其分子机制,可为今后的研究提供依据和方向.

Fermented Chinese medicine has long been used. Amid the advance for preservation of experience, the connotation of fermented Chinese medicine has been enriched and improved. However, fermented Chinese medicine prescriptions generally contain a lot of medicinals. The fermentation process is complicated and the conventional fermentation conditions fail to be strictly controlled. In addition, the judgment of the fermentation end point is highly subjective. As a result, quality of fermented Chinese medicine is of great difference among regions and unstable. At the moment, the quality standards of fermented Chinese medicine are generally outdated and different among regions, with simple quality control methods and lacking objective safe fermentation-specific evaluation indictors. It is difficult to comprehensively evaluate and control the quality of fermented medicine. These problems have aroused concern in the industry and also affected the clinical application of fermented Chinese medicine. This article summarized and analyzed the application, quality standards, and the modernization of fermentation technology and quality control methods of fermented Chinese medicine and proposed suggestions for improving the quality standards of the medicine, with a view to improving the overall quality of it.

为了更好地推进"以学生为中心"的"药事管理与法规"的课堂教学,结合中医药院校培养高素质创新型应用型人才的目标,通过对"药事管理与法规"教学现状的分析,将课程思政和多元教学法相结合,旨在转变以教师为中心的单向灌输式传统教学模式,培养综合型高素质中医药特色人才,提高"药事管理与法规"教学质量.

对《中华人民共和国药典》2020版一部所收载的处方中含冰片、薄荷或其加工品的成方制剂进行了统计,共305种,占一部成方制剂总量的18.98％.针对成方制剂中冰片、薄荷质量控制情况,分别对鉴别方法、含量测定方法进行了总结,发现两者的质量控制均以薄层色谱法鉴别、气相色谱法含测为主,方法较为成熟但也存在制剂中未对两药进行质量控制的情况.对含冰片、薄荷的中药成方制剂收载品种情况、入药方式、鉴别检查、含量测定及注意事项等内容进行分类统计,总结冰片、薄荷质量控制的现状、规律和不足,以期为含冰片、薄荷的中药成方制剂质量全面控制提供参考和借鉴.

雷公藤甲素是从卫茅科雷公藤根部提取的一种环氧二萜内酯化合物,已经证实具有抗炎、抗病毒、免疫调节、抗生育等多种药理活性,近年来,尤其在抗肿瘤方面显示出巨大潜力.雷公藤甲素对多种肿瘤细胞具有显著抑制作用,其作用机制包括抑制肿瘤细胞增殖与迁移、诱导肿瘤细胞凋亡、诱导肿瘤细胞自噬、诱导肿瘤细胞周期阻滞等.但其水溶性差、生物利用度低及不良反应严重等缺陷限制其临床应用,目前通过纳米制剂手段如脂质纳米粒、聚乳酸纳米粒、聚合物胶束、外泌体等,可将药物精准递送到肿瘤部位,提高药物疗效,降低毒性等,其展现出良好的应用前景.本文通过对近年来国内外雷公藤甲素的抗肿瘤活性、作用机制及其纳米制剂抗肿瘤应用的研究进行归纳总结,以期为雷公藤甲素及其纳米制剂在抗肿瘤方面的进一步开发应用提供指导.

重楼作为我国传统的名贵中药材,主要分布在云南、广西、贵州等西南一带,具有清热解毒、消肿止痛、凉肝定惊的功效,治疗铁打伤痛、毒蛇咬伤、凉风抽搐等具有奇效,迄今已经有2 000多年的应用历史.重楼皂苷Ⅱ结构上属于薯蓣皂苷,是重楼的主要活性成分之一,具有抗肿瘤、抗炎、抗病毒、抗菌、免疫调节、抗氧化、逆转多药耐药等多种药理活性,展现出良好的应用前景.其中,重楼皂苷Ⅱ的抗肿瘤作用受到广泛关注,其作用机制与抑制增殖、迁移和侵袭,诱导细胞周期阻滞、凋亡和自噬,抑制血管生成,调节肿瘤微环境等有关.药代动力学显示,重楼皂苷Ⅱ由于其溶解度低、吸收差、体内分布不理想、代谢慢等因素,导致其体内生物利用度低,严重限制其临床应用.近年来,重楼皂苷Ⅱ的不良反应报道增多,如具有较强的溶血活性,并对肝、肾、心肌、心血管细胞等产生明显细胞增殖抑制作用.以"重楼皂苷Ⅱ""Polyphyllin Ⅱ""Paris Saponin Ⅱ"为主要关键词,通过检索"中国知网""维普""万方""PubMed""Web of Science""Elsevier SD"等中英文数据库,现从药理作用及其机制、药代动力学研究、不良反应3个方面对其研究进展进行综述,以期为重楼皂苷Ⅱ的深入研究和开发利用提供思路和参考.

目的 建立景参浓缩丸高效液相色谱(HPLC)指纹图谱,并对丹酚酸B、柚皮苷、新橙皮苷进行含量测定.方法 采用Agilent Eclipse Plus C18色谱柱(4.6 mm × 250 mm,5 μm);流动相为甲醇-0.1％磷酸水,梯度洗脱;检测波长278 nm;流速1.0 mL·min-1;柱温35℃;进样量10μL,根据11批样品的色谱图数据建立景参浓缩丸的指纹图谱并确立共有峰;通过HPLC法测定基准样品中丹酚酸B、柚皮苷、新橙皮苷的含量.结果 11批景参浓缩丸的HPLC图谱中有23个共有峰,相似度＞0.99,指认了其中红景天苷、特女贞苷、丹酚酸B、柳穿鱼叶苷、柚皮苷、新橙皮苷、丹参酮Ⅰ、隐丹参酮、丹参酮ⅡA 9个色谱峰成分;所建立的3种指标成分含量测定方法稳定性、重复性、线性关系、加样回收率良好,符合要求.结论 所建立的景参浓缩丸HPLC指纹图谱和指标成分的含量测定方法具有良好的稳定性和重复性,可为景参浓缩丸质量控制提供参考.

Ethnopharmacological relevance: Xiaoer Huanglong Granule (XHG), a Traditional Chinese Medicine formula, has been widely used in the clinic for treating attention deficit hyperactivity disorder (ADHD) patients with ying deficiency and yang hyperactivity. It has 11 crude materials: Paeoniae Radix Alba, Rehmanniae Radix Preparate, Schisandrae Chinensis Fructus, Codonopsis Radix, Rhizoma Anemarrhenae, Polygalae Radix, Platycodonis Radix, Ophiopogonis Radix, Acori Tatarinowii Rhizoma, Fossilia Ossis Mastodi and Concha Ostreae. As a successfully marketing Chinese Patent Medicine, XHG has been selected into the National Reimbursement Drug List and been covered by medical insurance category B in China.Aim of the study: After previous comprehensively analyzing the components of XHG, a study on the mechanism of XHG treating ADHD needs to be further explored by network pharmacology study and biochemical tests.Materials and methods: We investigated the neuroprotective effects of XHG against ADHD by network pharmacology, open field test, elevated plus maze test and western blot assay based on our previous phytochemical identification of XHG.Results: Methyl-L-phenylalanine (degree=20), 1,4-β-D-Mannotriose (degree=15), Aurantiamide acetate (degree=13), N-cis-FeruloyltyraMine (degree=13), Timosaponin A-Ⅲ (degree=11) and Apigenin (degree=11) were predicted as top 6 active components, while TH, ADORA2A, SLC6A3, SLC6A4, and COMT were selected as 5 putative related proteins by construction of the component-disease-target and protein–protein interactions network, respectively. The above active compounds could be well combined with the targets by the calculation of AutoDock Vina and PyMol. The results of behavioral tests and western blot assay showed the therapeutic effect of XHG on motor hyperactivity, impulsive-like behaviors and regulation of neurotransmitter system proteins levels.Conclusions: This was the first study that exhaustively analyzed the potential active components, targets, and pathways of XHG in treating ADHD and showing neuroprotective effects via network pharmacology, behavioral tests and western blot assay.

As arsenic widely exists in nature and has been used in the pharmaceutical preparations, the traditional Chinese medicine(TCM) with arsenic include realgar(As_2S_2 or As_4S_4), orpiment(As_2S_3), and white arsenic(As_2O_3). Among the above representative medicine, the TCM compound formulas with realgar are utilized extensively. Just in Chinese Pharmacopoeia(2020 edition), there are 37 Chinese patent medicines including realgar. The traditional element analysis focuses on the detection of the total amount of elements, which neglects the study on the speciation and valence of elements. The activity, toxicity, bioavailability, and metabolic pathways of arsenic in vivo are closely related to the existence of its form, and different forms of arsenic have different effects on organisms. Therefore, the study on the speciation and valence of arsenic is of great importance for arsenic-containing TCMs and their compound formulas. This paper reviewed four aspects of the speciation and valence of arsenic, including property, absorption and metabolism, toxicity, and analytical assay.

中药的本草考证在经典名方的开发中发挥着重要作用.查阅文献发现,现代对旋覆花的研究多集中在化学成分及药理作用等方面,对其名称、基原、产地变迁、采收加工、炮制、药用部位及功效的本草考证仍缺乏报道.经查阅历代本草、医籍、方书,古今所用旋覆花均为菊科植物旋覆花Inula japonica Thunb.的干燥头状花序.在历代本草中旋覆花分布广泛,在明代明确道地产区为河南及湖南,近代在广西、广东等地也有出产.现代资源调查结果发现,旋覆花生于海拔150～2400 m的山坡路旁、湿润草地、河岸和田埂上.旋覆花极少以生品入药,多花开后晒干或采用其炮制品入药.根据考证结果,建议旋覆花选取菊科植物旋覆花Inula japonica Thunb.为基原,以其干燥头状花序入药,未注明特殊要求均可参考《中国药典》处理.

At present, several experiments have been carried out to study the changes in total arsenic content of realgar and its prescription, but few researches on its form and valence. We evaluated the change in arsenic species concentration in realgar from the perspective of absorption by using an in vitro dissolution study, an in vivo unidirectional intestinal perfusion study, transmembrane transport in Caco-2 cells, and a pharmacokinetic study in rats. In the gastrointestinal tract, arsenic species are mainly present inorganic forms of AsIII and AsV. The cumulative dissolution rates of soluble arsenic in 4 h artificial gastric fluid and 8 h artificial intestinal fluid were 21.99% and 59.20%, respectively. The Papp values of soluble arsenic in realgar in the duodenum, jejunum, and ileum of rats were 5.4×10, 6.1× 10 and 5.8×10 cm/min, respectively. In the process of small intestine perfusion, the AsIII of realgar was partially converted into AsV in the duodenum and jejunum. As the transport time increased, the transmembrane transport rate and Papp value of soluble arsenic in realgar were increased in Caco-2 cells, and it also suggested that arsenic species may be passively transported across the Caco-2 cell monolayer. The Cmax and AUC (0-24) of AsIII, AsV, and DMA in plasma of realgar were 41.26 ng L/343.977 ng hmL, 21.626 ng L/47.310 ng hmL, and 2.372 ng L/ 30.429 ng hmL, respectively. Tmax and MRT (0-∞) of AsIII, AsV, and DMA were 2.571 h/9.649 h, 0.393 h/2.790 h, and 3.143 h/23.145 h, respectively. It is hoped to provide a basis for clarifying the arsenic species in realgar.

At present, several experiments have been carried out to study the changes in total arsenic content of realgar and its prescription, but few researches on its form and valence. We evaluated the change in arsenic species concentration in realgar from the perspective of absorption by using an in vitro dissolution study, an in vivo unidirectional intestinal perfusion study, transmembrane transport in Caco-2 cells, and a pharmacokinetic study in rats. In the gastrointestinal tract, arsenic species are mainly present inorganic forms of AsIII and AsV. The cumulative dissolution rates of soluble arsenic in 4 h artificial gastric fluid and 8 h artificial intestinal fluid were 21.99% and 59.20%, respectively. The P app values of soluble arsenic in realgar in the duodenum, jejunum, and ileum of rats were 5.4 × 10 −3 , 6.1 × 10 −3 and 5.8 × 10 −3  cm/min, respectively. In the process of small intestine perfusion, the AsIII of realgar was partially converted into AsV in the duodenum and jejunum. As the transport time increased, the transmembrane transport rate and P app value of soluble arsenic in realgar were increased in Caco-2 cells, and it also suggested that arsenic species may be passively transported across the Caco-2 cell monolayer. The C max and AUC (0-24) of AsIII, AsV, and DMA in plasma of realgar were 41.26 ng L −1 /343.977 ng h mL −1 , 21.626 ng L −1 /47.310 ng h mL −1 , and 2.372 ng L −1 /30.429 ng h mL −1 , respectively. T max and MRT (0-∞) of AsIII, AsV, and DMA were 2.571 h/9.649 h, 0.393 h/2.790 h, and 3.143 h/23.145 h, respectively. It is hoped to provide a basis for clarifying the arsenic species in realgar.

目的:建立高效液相色谱(HPLC)法同时测定景参丸中红景天苷和丹酚酸B的含量,并优化景参丸的干燥工艺.方法:①采用Agilent ZORBAX Eclipse Plus C18色谱柱(250 mm×4.6 mm,5μm),以甲醇-0.1％磷酸水溶液为流动相进行梯度洗脱,流速1 ml/min,检测波长278 nm,柱温35℃,进样体积10μl.并进行方法学考察.②以丸剂外观、水分、溶散时限以及红景天苷和丹酚酸B的含量为评价指标,考察室温(25℃)除湿干燥、60℃热风干燥、70℃热风干燥、80℃热风干燥、90℃热风干燥及100℃热风干燥对景参丸质量的影响,采用综合评分法优选最佳干燥工艺.结果:①所建立的含量测定方法,线性关系、精密度、重复性、稳定性、加样回收率等均符合要求.②优选的景参丸最佳干燥工艺为70℃热风烘干干燥,铺层厚度1.5 cm,干燥时间2h.结论:所建立的含量测定方法简便,重复性和稳定性好,精密度高,可为景参丸的质量控制提供参考.优选出的景参丸干燥工艺稳定、可行,可最大限度保留有效成分,且干燥效率高.

作为名贵中药材,麝香、牛黄常用于急重症患者的救治,但因二者来源稀缺、价格昂贵,野生动物资源急需保护,天然麝香和牛黄已经无法满足制剂生产的需要,人工麝香、人工牛黄、体外培育牛黄等代用品的使用在一定程度上缓解了原药材紧张的问题,目前已被广泛用于中药制剂的生产和使用.2020年版《中华人民共和国药典》(以下简称《中国药典》)共收载了 75个中药制剂含有麝香,95个制剂含有牛黄,但在这134个中药制剂的质量标准中,对天然药材与其代用品的区别并不十分明显,部分质量控制项目较为简单.笔者通过梳理2020年版《中国药典》(一部)所载含麝香、牛黄的中药制剂的质量标准情况,包括制剂中麝香或牛黄的类型、入药形式、处方用量、每日(次)最大服用量及质量控制项目等,探讨含麝香、牛黄的中药制剂质量标准的合理性,并在规范麝香和牛黄的使用类型、结合现代研究成果和先进技术完善中药制剂中麝香、牛黄的质量控制项目等方面给出建议,以期能够科学认识、评价含有麝香和牛黄的中药制剂,并为此类中药制剂的质量标准提高提供参考.

目的:探讨珍珠明目滴眼液(ZMED)对肿瘤坏死因子α(TNF-α)和干扰素γ(IFN-γ)诱导人角膜上皮细胞(HCEC)损伤的保护作用及相关机制.方法:采用150 ng/mL的TNF-α和IFN-γ(1:1)溶液刺激离体培养的HCEC建立干眼损伤模型,药物组分别给予稀释倍数为1 000、100、50倍的ZMED;分别采用MTT实验检测ZMED对TNF-α和IFN-γ诱导损伤HCEC的保护作用;采用AO/EB双染法和Hoechst荧光染色法观察各组细胞凋亡形态的差异;采用流式细胞术分析各组细胞凋亡率及细胞周期分布;通过Western Blot检测凋亡相关蛋白表达水平的变化.结果:ZMED稀释50倍即可以明显增加TNF-α和IFN-γ诱导损伤的HCEC的存活率;ZMED稀释100倍以下可呈浓度依赖性地降低HCEC凋亡率并抑制其G2期阻滞(P＜0.05);ZMED给药后cleaved Caspase-8、cleaved Caspase-3、PARP、p-ERK1/2/ERK1/2下调(P＜0.05),Bcl-2/Bax上调(P＜0.05).结论:ZMED对 150 ng/mL的TNF-α和IFN-γ溶液诱导损伤的HCEC有明显的保护作用,该作用可能与其抑制Caspase-8/Caspase-3信号通路,Bcl-2家族蛋白与ERK1/2的活化相关.

Chinese Pharmacopoeia is an important part of drug standards in China, and it is also a legal basis that must be strictly followed in drug development, production, operation, application, and management. The information on prescriptions, preparation methods, properties, identification, inspection, content determination, functions and indications, usage and dosage, precautions, specifications, and storage of Chinese patent medicine preparations included in the Chinese Pharmacopoeia(Vol.Ⅰ) was clarified. The "Preparation Method" section describes the preparation process of Chinese patent medicine from decoction pieces to finished preparations in detail and specifies the preparation production methods and parameters, which has a good guiding and standardizing effect on the production of Chinese patent medicine in China. The present study summarized the preparation methods of Chinese patent medicine preparations and single drug preparations contained in the Chinese Pharmacopoeia(2020 edition, Vol.Ⅰ) in stages and analyzed the common preparation methods and technical parameters of Chinese patent medicine preparations, which is helpful to understand the current situation of Chinese patent medicine production technology in China and can provide references for the development of new Chinese medicine, the transformation of large varieties of Chinese patent medicine, and the optimization of preparation process of Chinese patent medicine in the market.