Background. Gecko has been widely documented in Chinese scientific literature as an anti-tumor agent for various illnesses for thousands of years, and more recently, it has been examined for its anti-tumor effects on several cancers. The effect of Gecko microRNAs (miRNAs) on hepatocellular carcinoma (HCC) has not yet been reported. Objectives. This study was designed to identify miRNAs in Gecko through small RNA sequencing and utilize bioinformatics techniques to construct a potential regulatory network and explore the possible mechanisms of exogenous miRNAs involved in HCC. Materials and methods. RNA was extracted from Gecko tablets, and we screened the Gecko miRNA expression dataset after high-throughput sequencing. Bioinformatics analysis was used to identify novel Gecko and HCC survival-related miRNA-mRNA cross -species regulation networks. Results. miR-100-5p, miR-99a-5p and miR-101-3p were identified as critical for the role of Geckos in HCC. Nine downstream mRNAs ( EZH2 , KPNA2 , LMNB1 , LRRC1 , MRGBP , SMARCD1 , STMN1 , SUB1 , and UBE2A ) were identified as target genes for critical miRNAs. A miRNA-mRNA regulatory network was constructed, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed these key mRNAs might be associated with both the suppression and progression of HCC. The novel network significantly correlated with the abundance of multiple immune cells, as determined with immune infiltration analysis. Conclusions. These findings suggest that Gecko may inhibit progression and exert a therapeutic effect on HCC by targeting critical miRNA-mRNA networks for cross -species regulation. It also provides a reference for future research and development of traditional Chinese medicine (TCM).

BACKGROUND:In traditional Chinese medicine (TCM), frankincense and myrrh are the main components of the antitumor drug Xihuang Pill. These compounds show anticancer activity in other biological systems. However, whether frankincense and/or myrrh can inhibit the occurrence of hepatocellular carcinoma (HCC) is unknown, and the potential molecular mechanism(s) has not yet been determined.AIM:To predict and determine latent anti-HCC therapeutic targets and molecular mechanisms of frankincense and myrrh in vivo.METHODS:In the present study, which was based on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (http://tcmspw.com/tcmsp.php), Universal Protein database (http://www.uniprot.org), GeneCards: The Human Gene Database (http://www.genecards.org/) and Comparative Toxicogenomics Database (http://www.ctdbase.org/), the efficacy of and mechanism by which frankincense and myrrh act as anti-HCC compounds were predicted. The core prediction targets were screened by molecular docking. In vivo, SMMC-7721 human liver cancer cells were transplanted as xenografts into nude mice to establish a subcutaneous tumor model, and two doses of frankincense plus myrrh or one dose of an EGFR inhibitor was administered to these mice continuously for 14 d. The tumors were collected and evaluated: the tumor volume and growth rate were gauged to evaluate tumor growth; hematoxylin-eosin staining was performed to estimate histopathological changes; immunofluorescence (IF) was performed to detect the expression of CD31, α-SMA and collagen IV; transmission electron microscopy (TEM) was conducted to observe the morphological structure of vascular cells; enzyme-linked immunosorbent assay (ELISA) was performed to measure the levels of secreted HIF-1α and TNF-α; reverse transcription-polymerase chain reaction (RT-qPCR) was performed to measure the mRNA expression of HIF-1α, TNF-α, VEGF and MMP-9; and Western blot (WB) was performed to determine the levels of proteins expressed in the EGFR-mediated PI3K/Akt and MAPK signaling pathways.RESULTS:The results of the network pharmacology analysis showed that there were 35 active components in the frankincense and myrrh extracts targeting 151 key targets. The molecular docking analysis showed that both boswellic acid and stigmasterol showed strong affinity for the targets, with the greatest affinity for EGFR. Frankincense and myrrh treatment may play a role in the treatment of HCC by regulating hypoxia responses and vascular system-related pathological processes, such as cytokine-receptor binding, and pathways, such as those involving serine/threonine protein kinase complexes and MAPK, HIF-1 and ErbB signaling cascades. The animal experiment results were verified. First, we found that, through frankincense and/or myrrh treatment, the volume of subcutaneously transplanted HCC tumors was significantly reduced, and the pathological morphology was attenuated. Then, IF and TEM showed that frankincense and/or myrrh treatment reduced CD31 and collagen IV expression, increased the coverage of perivascular cells, tightened the connection between cells, and improved the shape of blood vessels. In addition, ELISA, RT-qPCR and WB analyses showed that frankincense and/or myrrh treatment inhibited the levels of hypoxia-inducible factors, inflammatory factors and angiogenesis-related factors, namely, HIF-1α, TNF-α, VEGF and MMP-9. Furthermore, mechanistic experiments illustrated that the effect of frankincense plus myrrh treatment was similar to that of an EGFR inhibitor with regard to controlling EGFR activation, thereby inhibiting the phosphorylation activity of its downstream targets: the PI3K/Akt and MAPK (ERK, p38 and JNK) pathways.CONCLUSION:In summary, frankincense and myrrh treatment targets tumor blood vessels to exert anti-HCC effects via EGFR-activated PI3K/Akt and MAPK signaling pathways, highlighting the potential of this dual TCM compound as an anti-HCC candidate.

Abstract Gecko is a traditional Chinese herb that has been extensively documented as a treatment for various illnesses, including cancer, for thousands of years in ancient Chinese literature. The development of Chinese medicinal preparations and the role of small molecule active ingredients in Chinese medicine have recently emerged as new research hotspots. However, the potential cross-species regulatory mechanisms of microRNAs (miRNAs) from Gecko components in hepatocellular carcinoma (HCC) are not fully understood. In this study, we isolated and extracted total RNA from Chinese herbal Gecko tablets after powdering and screened the Gecko miRNA expression dataset after high-throughput sequencing to compare with the survival-related differentially expressed miRNA dataset in human HCC to identify new Gecko and HCC survival-related miRNA-mRNA regulatory networks. The miR-100-5p, miR-99a-5p, and miR-101-3p were identified as critical miRNAs for the role of Geckos in human HCC. Stepwise prediction and validation, nine downstream mRNAs (EZH2, KPNA2, LMNB1, LRRC1, MRGBP, SMARCD1, STMN1, SUB1, and UBE2A) were found to be determined as key miRNAs interacting with essential genes that interact with each other. A miRNA-mRNA regulatory network consisting of these key genes was constructed, and GO, KEGG enrichment analysis indicated that these key mRNAs might be associated with the suppression and progression of hepatocellular carcinoma. Importantly, immune infiltration analysis showed that the miRNA network was significantly associated with the infiltration abundance of multiple immune cells. These findings suggest that Gecko miRNAs may inhibit HCC progression and treat HCC by targeting critical miRNA-mRNA networks for cross-species regulation. It also provides a reference for future research and new drug development.

鳖甲是临床常用药物,现代对鳖甲的研究主要聚焦于实验研究及临床观察,鲜见文献研究.该文在系统查阅鳖甲古今文献的基础上,通过分析历代本草方书中的相关内容,对鳖甲的名称、基原、产地、品质评价、功效主治、炮制方法及用药禁忌进行全面考证.通过考证发现,在基原上,古籍文献所载的鳖甲当来源于中华鳖Trionyx sinensis的背甲,山瑞鳖T.steindachneri的背甲不宜作为中药鳖甲的来源.鳖甲的道地产区在今长江中下游的岳阳、荆州、安徽东南部及江苏西部.关于鳖甲的品质评价,本草古籍中常以鳖甲的肋数如七肋、九肋作为品质评价的标准,但通过文献研究及对药材市场的实地考察,发现以肋数作为品质的评价标准在现代并不可取.随着时代的更迭,鳖甲的功效主治在《神农本草经》的基础上逐渐扩展,后世将鳖甲广泛应用于内外妇儿各科.需要注意的是,鳖甲治劳热骨蒸当来源于《神农本草经》,而不是《本草衍义》等古籍所言的《药性论》.在炮制方面,鳖甲炮制方法多样,主要以醋制为主.在用药禁忌方面,鳖甲不能与矾石、理石配伍,孕妇禁用,脾虚胃弱、肝虚无热者慎用.该文的考证结果为鳖甲的正本清源及进一步资源开发利用提供了参考依据.

目的 初步分析虫类药治疗肝癌的用药规律.方法 从中国知网、万方数据库、维普数据库检索筛选出含虫类药治疗肝癌的处方,利用中医传承辅助平台(V2.5)分析其用药规律.结果 筛选出186首治疗肝癌的含虫类药处方,涉及中药221味,其中虫类药35味,高频虫类药为鳖甲、牡蛎、土鳖虫等;虫类中药多与补虚类药、解毒类药、化瘀类药、化湿类药、理气类药等配伍使用,处方中常用虫类药药味数为1-3味,药性以寒、温、平为主,五味以咸、甘为主,近1/3的虫类药均有毒性,主入肝、肾、心、胃、脾经.获得使用频次≥20次的常用含虫类药物药对47对,药物关联规则20条.基于复杂系统熵聚类分析,得到含虫类药物新方核心组合12个,治疗肝癌的候选新处方6个.结论 运用含虫类处方治疗肝癌常用鳖甲、牡蛎、土鳖虫等虫类药,其疗效确切、效专力猛,多与益气健脾、利水渗湿等功效的药物联用,契合病机,体现了肝癌扶正祛邪之大法,为临床用药提供一定的参考和借鉴.

对比研究《武威汉代医简》与《五十二病方》中使用的液体辅料及其所治疗的疾病,并与后世中医药典籍进行对比,研究异同,以便于指导临床治疗及进行进一步的文献、科学研究.

目的 运用网络药理学方法及分子对接技术对雷公藤治疗肝癌的主要活性成分及其潜在作用机制进行探讨.方法 通过中药系统药理学数据库与分析平台(TCMSP)筛选雷公藤主要活性成分及其预测靶点;在DrugBank、GeneCards、OMIM、TTD数据库中筛选肝癌相关靶点;通过R语言软件映射得到雷公藤治疗肝癌靶点,并绘制韦恩图;在STRING网站构建治疗靶点PPI网络图;应用Cytoscape软件构建"雷公藤-活性成分-靶点-肝癌"互作网络图;通过R语言软件对治疗靶点进行GO功能分析和KEGG通路富集分析;应用PubChem、RCSB PDB数据库,AutoDock、PyMOL软件对药物潜在活性成分与关键靶点进行分子对接.结果 共筛选出活性成分51个和潜在治疗靶点120个,靶点主要涉及酰胺结合、肽结合、DNA结合转录因子结合等生物学过程,并主要富集于卡波西肉瘤相关疱疹病毒感染、乙型肝炎、流体剪切应力和动脉粥样硬化等信号通路中.分子对接验证显示对接得分大于-5kcal/mol占100％,即所有靶点与成分的结合活性较好.结论 通过网络药理学方法及分子对接技术证实了雷公藤多成分、多靶点、多途径的作用特点,预测了雷公藤治疗肝癌的潜在作用机制,为后续进一步开发和应用提供理论依据.

肿瘤目前已成为危害人类生命健康的主要疾病之一.研究表明,龟鹿二仙胶可通过增强机体对肿瘤细胞的免疫、降低肿瘤细胞耐药性、改善骨髓抑制,从而发挥抗肿瘤作用,而成方中单药抗肿瘤作用亦可通过诱导细胞凋亡、抑制新生血管形成等多种途径来实现.虽然龟鹿二仙胶抗肿瘤机制研究已取得一定进展,但主要聚焦于免疫系统,今后需进一步研究其相关作用机制,为肿瘤临床治疗拓宽思路和方法.

辅料与临床疗效密切相关,《五十二病方》是现存最早的记载辅料应用的方书.该书广泛应用了酒、醋、蜜、人尿等8种液体辅料治疗疾病.本文通过文献研究,归纳出《五十二病方》各种液体辅料的适应症,并将其与后世经典本草著作中功效主治相对比,分析其异同,以期为研究液体辅料功效主治的演变及临床应用提供参考.

壁虎和石龙子药用历史悠久,但长期以来两者常混为一谈,而现代对两者的研究主要集中在临床观察、有效成分及抗癌机制等方面,鲜见文献研究.该文在系统查阅壁虎和石龙子古今文献的基础上,通过分析历代本草方书中的相关内容,对两者的名称、基原、功效主治、炮制方法及用药禁忌进行全面考证.通过考证发现,在先秦,壁虎与石龙子被当作同一物,至汉代则知两者为不同的动物,到三国时期两者又被混淆,直至明代《本草纲目》才明确两者的关系.在基原上,石龙子的基原包括蜥蜴科丽斑麻蜥Eremias argus,山地麻蜥E.brenchleyi及石龙子科中国石龙子Eumeses chinensis.壁虎的基原包括多疣壁虎Gekko japonicus,铅山壁虎G.hokouensis,无蹼壁虎G.swinhonis及蹼趾壁虎G.subpalmatus.功效主治方面,历代本草记载石龙子的主要功效为利水,壁虎的主要功效为祛风、化瘀.在炮制上壁虎与石龙子有多种炮制方法,但主要以传统"火制法"为主.关于用药禁忌,古籍文献记载石龙子恶硫黄、芜荑、斑蝥,孕妇忌用;壁虎慎用于血虚气弱之人.该文的考证结果厘清了壁虎和石龙子从名称、功效主治到炮制等多方面的历史沿革,为壁虎及石龙子的正本清源及进一步开发利用提供了理论依据.

目的 利用网络药理学方法对黄芪进行多成分、多靶点研究,分析其在卒中相关性肌少症中的作用靶点及相关通路.方法 采用TCMSP数据库收集黄芪活性化合物并进行初步筛选;采用Swiss Target Prediction数据库预测活性化合物靶点,通过GeneCards数据库预测卒中相关性肌少症作用靶点,取两者交集获得交互靶点.采用String数据库及Cytoscape软件Network analyzer功能构建共同靶点PPI网络.采用DAVID数据库并结合Cytoscape软件对共同靶点进行GO及KEGG富集分析.结果 收集筛选出黄芪20个活性化合物,616个作用靶点,卒中相关性肌少症136个作用靶点,交集出25个交互靶点,其中AKT1、IL-6、TNF、IGF1R、ESR1等蛋白相互作用最明显,主要在细胞基质中影响类固醇结合、锌离子结合、蛋白质丝氨酸/苏氨酸激酶活性、雌激素受体活性、胰岛素及能量代谢等生物过程,通过胰岛素抵抗、HIF-1信号通路、TNF信号通路等在卒中相关性肌少症中发挥作用,AKT1、PI3CG、mTOR、IL-6、TNF等交互靶点在各通路中参与次数较多.结论 黄芪在卒中相关性肌少症中体现了多成分、多靶点、多途径的特点,其可能通过调控IRS-1/PI3K/AKT2/mTOR信号通路,靶向调控胰岛素抵抗途径相关能量代谢障碍,进而治疗和预防卒中相关性肌少症.

Objective: To explore brain activations associated with electroacupuncture simulation at Tongli (HT 5) and its comparison with brain activations during picture-naming task. Methods: Twenty healthy subjects were enrolled in this study. Half of them received electroacupuncture stimulation at HT 5 (ACUP group) and the other half of them received stimulation at a nonmeridian sham acupoint (SHAM group). All subjects performed picture-naming task. Each subject finished two runs of functional magnetic resonance imaging examinations in one session and picture-naming task was performed before electroacupuncture stimulation. Subjective brain activations were obtained using generalized linear model and inter-group analyses were performed after that. Results: The electroacupuncture stimulation at HT 5 induced significant brain activations in both the anterior and posterior language regions, including the left inferior frontal gyrus, which was in consistent with activations induced during picture-naming task. Group analysis showed a tendency of increased activation of ACUP group in left inferior frontal gyrus compared with SHAM group (P<0.05 FDR corrected). Conclusions: Electroacupuncture treatment at the acupoint HT 5 has modulation effect on typical language-implicated brain regions in healthy subjects, which provides supporting evidence for beneficial effects of needling at HT 5 for recovery of language function in aphasia.

脑梗死是神经系统的常见病、多发病,约占脑血管疾病的65％.脑梗死的高致残率、高死亡率与梗死后缺血再灌注损伤机制,如钙超载、氧化/氮化应激、线粒体功能紊乱、炎症等密切相关.同时研究表明内质网应激在脑梗死过程中亦起着重要作用,并且缺血再灌注损伤与内质网应激之间存在密切联系.综述近几年脑梗死缺血再灌注损伤机制与内质网应激的研究进展及其相互影响.

张士骧、张山雷、张锡纯为清末民初三大医家,三者在“西学东渐”的大背景下,对“脑出血”的认识不断深入,阐述了脑出血的病因病机及遣方用药原则.本文将“三张”对该病认识的异同做了全面的叙述,为广大中医临床工作者提供参考.

Objective To evaluate the effectiveness of GuiPi decoction for insomnia. Methods All randomized controlled trials( RCTs) and quasi-RCTs on GuiPi decoction for insomnia were searched in the VIP,CNKI,CBM disc and Wan fang data. The quality of RCTs meeting inclusion criteria was evaluated and the related data were extracted. Meta-analyses were performed with RevMan 4. 2. 7 software. Results A total of 12 trials were included in this study,including 1004 cases. Meta-analyses showed that total effective rate OR = 4. 08,95% CI[2. 72-6. 13]. Conclusion The present evidence showed that GuiPi decoction for insomnia has a better efficacy but key outcome should be evaluated.For the low quality and potential publication bias of included study,large-scale,the studies of high-quality researches and with TCM features should be performed.