湖南二号方调节机体免疫防治新型冠状病毒肺炎的网络药理学研究

目的:应用网络药理学方法探究湖南二号方通过增强免疫力防治新型冠状病毒肺炎(COVID-19)感染的作用与机制。方法:通过TCMSP等数据库筛选湖南二号方主要有效成分和潜在治疗靶点,通过GeneCards等数据库获取疾病基因,并将药物相关靶点与疾病靶点相互映射,通过Cytoscape3.8.0可视化筛选出核心基因,对共有靶点进行蛋白质相互作用网络构建、GO功能富集分析和KEGG通路富集分析。结果:湖南二号方中药-成分-靶点-疾病网络包括5味中药、99种活性成分和73个疾病靶点。其中湖南二号方治疗新型冠状病毒肺炎的靶点主要包括IL-6、VEGFA、ALB、CXCL8、MMP9和AKT1等。GO功能富集分析共得到条目1962个,主要涉及氧化应激反应和活性氧代谢过程等。KEGG通路富集分析筛选出145条信号通路,包括HIF-1、PI3K-Akt、TNF等信号通路。结论:湖南二号方中的槲皮素、山奈酚、异鼠李素活性成分可能通过介导HIF-1、IL-17等多条信号通路影响IL-6、VEGFA、ALB、CXCL8等靶蛋白的表达,发挥防治COVID-19的作用。

湖南一号方通过作用于ACE2防治新型冠状病毒肺炎的网络药理学研究

目的:基于新型冠状病毒主要受体-血管紧张素转化酶2(ACE2)应用网络药理学方法探究湖南一号方防治新型冠状病毒肺炎的作用与机制。方法:应用中药系统药理分析平台(TCMSP)检索湖南一号方中活性成分,结合药物靶点数据库搜索新型冠状病毒肺炎相关靶点,采用Cytoscape平台构建中药-活性成分-靶点-疾病网络,运用STRING和DAVID数据库对靶点的相互作用网络、GO功能和KEGG通路进行分析。结果:湖南一号方中药-活性成分-靶点-疾病网络包括8味中药,120种活性成分和90个疾病靶点。其中湖南一号方防治新型冠状病毒肺炎的靶点主要包括ALB、IL-6、VEGFA、CASP3、MAPK3、MMP9和CXCL8等。主要涉及生物过程中的氧化应激反应、活性氧代谢等,分子功能主要涉及细胞因子受体结合、细胞因子活性等,细胞组分主要涉及膜筏、膜微区等。上述靶点主要是参与HIF-1信号通路、IL-17信号通路、TNF信号通路等多条信号通路的调控。结论:湖南一号方可能通过介导HIF-1、IL-17等信号通路影响ALB、IL-6、VEGFA、CASP3等靶蛋白的表达,进而调节氧化应激反应、细胞因子活性等生物功能,发挥多成分-多靶点-多途径防治新型冠状病毒肺炎的作用。

SARS-CoV-2 Infected Cases with Untraceable Epidemic Origin:Its Values,Identification and TCM Treatment in Preventing Recurrence

During the outbreak of coronavirus disease 2019(COVID-19),the identification of a SARS-CoV-2 infected case with untraceable epidemic origin has three values:(1)the region has community transmission of the virus;(2)a certain portion of population in the community is getting immunized and more individuals have already been immunized;(3)an unpredictable future risk exists for regions where there are no infected cases with untraceable epidemic origin.Minimizing or avoiding the aggregation infection through individuals with no clinical symptoms is crucial and possible as its occurrence is mainly attributed to the local environment as opposed to the super spreader with or without clinical symptoms.As infected cases are not necessarily positive with gene test by definition,proper application of gene test is crucial in the identification of asymptomatic cases.In the early stage of an outbreak of infectious disease,gene test can be used to identify asymptomatic cases but it should not be used to exclude cases with typical clinical symptoms and signs.In the middle or late stages of an outbreak gene test should be applied in evaluation of infection rate of the population of a region,in addition to be used in spreader identification and isolation.Although asymptomatic cases are attributed to the overwhelming effect of personalized defense against pathogens,they are still a source of infection.Asymptomatic cases are considered to be Qi deficiency and with lingering toxicity in traditional Chinese medicine(TCM).Treatment in such cases,typically,involves therapy focused on replenishing the Qi,tonifying the lung,clearing the fever,and detoxification in order to return to a normal health condition.The recommended Chinese medicines include Qing Fei Pai Du Decoction,Yi Qi Qu Du Decoction,Xuan Fei Bai Du Granule,Lian Hua Qing Wen Capsule(Granule),and Jin Hua Qing Gan Granule,etc.

Effects of Xiaoxianxiong Tang on biological behavior in lung cancer cell line A549

Obiective:To investigate the effects of Xiaoxianxiong Tang on the proliferation,invasion,apoptosis,and other cell biological behaviors of non-small cell lung cancer A549 cells.Methods:Human lung adenocarcinoma A549 cells were cultured in vitro,and the IC50 concentration and effective time of administration of Xiaoxianxiong Tang were determined by the CCK-8 assay to detect the inhibitory effect of Xiaoxianxiong Tang on A549 cells proliferation.The effect of the Xiaoxianxiong Tang on apoptosis was determined by flow cytometry;the apoptosis-related protein was detected via Western blot;the metastasis-related protein mRNA was detected by RT-PCR.Results:Xiaoxianxiong Tang significantly inhibited the proliferation viability,the invasive ability,and the clonogenic ability of A549 cells compared with the control group(P<0.001).Moreover,Xiaoxianxiong Tang significantly promoted the apoptosis of A549 cells(P<0.001).Xiaoxianxiong Tang significantly up-regulated Bax and down-regulated Bcl2 expression in A549 cells compared with the control group(P<0.01).The mRNA expression of MMP2 and MMP9 was significantly down-regulated by Xiaoxianxiong Tang compared with the control group(P<0.05).Conclusion:Xiaoxianxiong Tang has the effect of regulating the biological behavior of A549 cells,and Xiaoxianxiong Tang significantly inhibites the proliferation viability,colony formation,and invasion ability of lung cancer A549 cells.

中药有效性评价新策略、新方法:整合证据链法

中药疗效评价问题是长期制约中医药发展壮大及国际化的“卡脖子”问题。该文从医学认知的底层逻辑出发,在系统剖析中西医药诊疗理念、药效物质基础、研发范式、疗效认知和评价模式等方面客观差异的基础上,整合临床经验、实验研究和临床试验的证据要素,首次提出并建立中药有效性评价新策略和方法体系——中药有效性评价整合证据链法(integrated evidence chain-based effectiveness evaluation of traditional Chinese medicine,iEC-Eff),形成中药有效性“临床经验-实验研究-临床试验”一体化评价与确证模式。初步应用研究显示,该方法可使中药特别是流传千年、有口皆碑、至今临床常用的经典名方的有效性评价等级得到科学提升,使其有效性证据等级能够更加客观地反映其临床价值和地位,突破了当今中药有效性评价以随机对照试验(RCT)为唯一“金标准”的局面及局限,为破解中药有效性评价难题提供了具有原创性和引领性的策略和方法,为建立中医药理论、人用经验和临床试验相结合的中药注册审评证据体系提供了具有可操作性的新工具。该方法可用于中医药经典名方有效性评价、中药新药研发、上市后中成药有效性再评价等,亦可供国家医保药物目录、国家基本药物目录等中药品种遴选参考。