背景众多证据表明免疫逃逸在肿瘤形成过程中扮演重要角色,慢性萎缩性胃炎(chronic atrophic gastritis,CAG)是胃癌的癌前疾病.安胃汤被发现可改善CAG临床症状及病理表现,实现CAG的逆转,该作用是否与免疫逃逸机制相关有待进一步研究.目...背景众多证据表明免疫逃逸在肿瘤形成过程中扮演重要角色,慢性萎缩性胃炎(chronic atrophic gastritis,CAG)是胃癌的癌前疾病.安胃汤被发现可改善CAG临床症状及病理表现,实现CAG的逆转,该作用是否与免疫逃逸机制相关有待进一步研究.目的从细胞免疫逃逸角度,探讨程序性死亡受体-1(programmed cell death protein 1,PD-1)/程序性死亡受体配体-1(programmed cell death ligand 1,PD-L1)信号轴与安胃汤对CAG模型大鼠疗效之间的关系.方法采用1-甲基-3-硝基-1-亚硝基胍(1-Methyl-3-nitro-1-nitrosoguanidine,MNNG)慢性萎缩性胃炎大鼠模型,应用不同剂量安胃汤及维酶素片进行干预;HE染色观察安胃汤对CAG模型大鼠胃黏膜炎症细胞浸润及组织形态改变的影响;免疫组化检测CAG模型大鼠胃黏膜组织PD-1、PD-L1蛋白表达;ELISA检测血清CD4^(+)、CD8^(+)水平变化;qPCR检测CAG模型大鼠胃黏膜PD-1mRNA、PD-L1mRNA表达;Western-blot检测CAG模型大鼠胃黏膜组织PD-1、PD-L1蛋白表达.结果免疫组化结果示:与模型组和维酶素组比较,安胃汤高、低剂量组PD-L1表达均较低(P<0.01,P<0.05).ELISA实验结果示:与模型组比较,安胃汤高剂量组CD4^(+)表达及CD4^(+)/CD8^(+)比值升高(P<0.01,P<0.05),安胃汤各组和维酶素组CD8^(+)表达降低(P<0.01);与维酶素组比较,安胃汤高剂量组CD8^(+)表达降低(P<0.05).qPCR实验结果显示:与模型组比较,安胃汤高剂量组和维酶素组PD-1mRNA表达下降(P<0.01),安胃汤高、中剂量组PD-L1mRNA表达下降(P<0.01,P<0.05).Western-blot实验结果显示:与模型组比较,安胃汤高、中剂量组PD-1/Actin,PD-L1/Actin表达下降(P<0.01,P<0.05).结论安胃汤抗CAG作用可能与抑制PD-1/PD-L1信号通路诱导的细胞免疫逃逸有关.展开更多
Objective:Doxorubicin is an efficient anthracycline drug for the treatment of tumor,however,its cardiotoxicity restricts the clinical application.Shenfu decoction has good clinical effect,but the pharmacological mecha...Objective:Doxorubicin is an efficient anthracycline drug for the treatment of tumor,however,its cardiotoxicity restricts the clinical application.Shenfu decoction has good clinical effect,but the pharmacological mechanism is not fully clarified.Method:The active components and potential targets of shenfu decoction were screened by TCMSP database,disease targets of doxorubicin-induced cardiotoxicity were collected by Genecards and OMIM database,and the network diagram of"drug-components-target-disease"was constructed by Cytoscape software.PPI network was constructed by STRING database.The target of action of the drug and the disease gene were mapped for GO and KEGG signal pathway analysis.Results:The study found that there are 52 main effective components of shenfu decoction,and 76 genes are involved in the potential therapeutic targets,among which 24 genes are potential targets of shenfu decoction in the treatment of doxorubicin-induced cardiotoxicity.The protein interaction network suggested that BCL2、BAX、CASP9、CASP3、MAPK8 may be the core target.GO enrichment analysis showed 52 cellular biological processes,and enrichment analysis of KEGG pathway revealed 99 involved signaling pathways,including TNF,apoptosis signaling pathways,etc.Conclusion:In this study,the network of"drug-components-target-disease"was constructed through network pharmacology,and it was found that the mechanism of"shenfu decoction"in the treatment of doxorubicin-induced cardiotoxicity involves multiple targets and pathways,which is conducive to guiding clinical medication.展开更多
Objective:The purpose of this thesis is to explore the mechanism of ShenFu Decoction in the treatment of critically ill patients with COVID-19 based on network pharmacology.Methods:The primary active ingredients and p...Objective:The purpose of this thesis is to explore the mechanism of ShenFu Decoction in the treatment of critically ill patients with COVID-19 based on network pharmacology.Methods:The primary active ingredients and potential targets of ShenFu Decoction were searched from the TCMSP database.The targets of COVID-19 were obtained by searching the GeneCards and OMIM databases.A ShenFu Decoction-compound-target-COVID19 network and a protein-protein interaction(PPI)network were respectively constructed through the Cytoscape 3.5.1 software and the STRING database.Gene Ontology(GO)function enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed via Bioconductor bioinformatics software package and R programming language.Results:ShenFu Decoction contains 255 compounds and 94 potential targets.43 primary active ingredients were searched from the TCMSP database with oral bioavailability(OB)≥30%and drug-likeness(DL)≥0.18 as the retrieval condition.Numbers of targets of COVID-19 were 352 by searching the GeneCards and the OMIM databases.16 key targets were acquired by intersecting the targets of drug with the targets of disease.There were 49 GO terms and 102 pathways after analyzing GO and KEGG.Conclusion:Kaempferol,ginsenoside rh2,beta-sitosterol,Stigmasterol and Deoxy andrographolide might be the main active ingredients which may cause the inhibition of the SARS-CoV-23CL hydrolase activity and regulate ACE2.As a result,the antiviral effect,immunoregulation,targeting cytokine storm of SFD may play an important role in the treatment of critically ill patients with COVID-19 through regulating multiple signaling pathways such as AGE-RAGE signaling pathway in diabetic complications,IL-17 signaling pathway,C-type lectin receptor signaling pathway,HIF-1 signaling pathway.展开更多
目的观察参附汤联合同种异体NK细胞(alloreactive naturall killer cells,alloNK)对移植小鼠术后外周血象、骨髓有核细胞计数(nucleated cell counts,NCC)、骨髓造血组织容量(hematopoietic volume of bone marrow,HV)及骨髓病理的影响...目的观察参附汤联合同种异体NK细胞(alloreactive naturall killer cells,alloNK)对移植小鼠术后外周血象、骨髓有核细胞计数(nucleated cell counts,NCC)、骨髓造血组织容量(hematopoietic volume of bone marrow,HV)及骨髓病理的影响。方法BALB/c小鼠经过13.0 Gy剂量的全身照射(total body irradiation,TBI),4 h内经尾静脉注入供鼠骨髓单个核细胞(mononuclear cells,MNCs)8×10^(6)/kg,制作移植小鼠模型,然后随机分为模型组、alloNK组、参附汤组、参附+alloNK组4组,分别给予生理盐水、单用alloNK、单用参附汤和参附汤联合alloNK灌胃,观察治疗前及治疗后第7、14、30天,小鼠外周血象、骨髓NCC、HV及组织病理的变化。结果移植前及移植后第7天各组小鼠外周血象、骨髓NCC、HV无显著性差异。移植后第14天,模型组小鼠白细胞仍处于粒缺期,而单纯alloNK组和参附组小鼠的白细胞均有所上升,参附联合alloNK组小鼠上升幅度高于其他组。移植后第30天,模型组、alloNK组及参附组小鼠白细胞、骨髓NCC、HV均较前回升,但仍低于移植前水平,而参附联合alloNK组小鼠的白细胞、骨髓NCC、HV恢复至移植前水平,与其他组相比差异显著。结论参附汤可保护骨髓免受放射损伤、促进造血功能恢复、缩短粒细胞缺乏时间,而联合alloNK细胞促进造血功能恢复的作用更明显。展开更多
目的观察补肾疏肝优化方治疗慢性乙型肝炎病毒(HBV)携带状态的临床疗效及对患者血清中程序性死亡受体1(PD-1)水平的影响。方法将86例慢性HBV携带状态患者随机分为治疗组和对照组,其中治疗组44例,对照组42例。治疗组给予补肾疏肝优化方治...目的观察补肾疏肝优化方治疗慢性乙型肝炎病毒(HBV)携带状态的临床疗效及对患者血清中程序性死亡受体1(PD-1)水平的影响。方法将86例慢性HBV携带状态患者随机分为治疗组和对照组,其中治疗组44例,对照组42例。治疗组给予补肾疏肝优化方治疗,对照组服用安慰剂,疗程为48周。观察两组患者治疗前后血清HBV DNA、e抗原(HBeAg)、表面抗原(HBsAg)、PD-1水平的变化及补肾疏肝优化方的临床疗效和安全性。结果试验过程中治疗组脱落1例,违背方案剔除3例,共纳入研究40例;对照组脱落2例,共纳入研究40例。治疗后,治疗组总有效率为32.50%(13/40),对照组总有效率为10.00%(4/40),治疗组总有效率明显高于对照组(P<0.05)。治疗后,治疗组患者的血清HBV DNA、HBeAg、HBsAg水平均较治疗前显著降低(P<0.05),且均低于对照组(P<0.05)。治疗后,治疗组HBeAg下降>0.5 lg、1 lg、2 lg COI的比例均高于对照组(P<0.05),治疗组HBeAg发生血清学转换的比例高于对照组,但差异无统计学意义(P>0.05)。治疗后,治疗组HBsAg下降>0.5 lg、1 lg COI的比例均高于对照组(P<0.05),治疗组HBsAg>2 lg COI的比例高于对照组,但差异无统计学意义(P>0.05)。治疗后,治疗组患者的血清PD-1水平较治疗前明显下降(P<0.05),且低于对照组(P<0.05)。两组患者治疗过程中安全性指标均未见明显异常。结论补肾疏肝优化方可在一定程度上降低慢性HBV携带状状态患者血清HBV DNA及病毒标志物水平,通过降低血清PD-1水平调节免疫,抑制HBV复制,疗效明显,安全性较好。展开更多
文摘背景众多证据表明免疫逃逸在肿瘤形成过程中扮演重要角色,慢性萎缩性胃炎(chronic atrophic gastritis,CAG)是胃癌的癌前疾病.安胃汤被发现可改善CAG临床症状及病理表现,实现CAG的逆转,该作用是否与免疫逃逸机制相关有待进一步研究.目的从细胞免疫逃逸角度,探讨程序性死亡受体-1(programmed cell death protein 1,PD-1)/程序性死亡受体配体-1(programmed cell death ligand 1,PD-L1)信号轴与安胃汤对CAG模型大鼠疗效之间的关系.方法采用1-甲基-3-硝基-1-亚硝基胍(1-Methyl-3-nitro-1-nitrosoguanidine,MNNG)慢性萎缩性胃炎大鼠模型,应用不同剂量安胃汤及维酶素片进行干预;HE染色观察安胃汤对CAG模型大鼠胃黏膜炎症细胞浸润及组织形态改变的影响;免疫组化检测CAG模型大鼠胃黏膜组织PD-1、PD-L1蛋白表达;ELISA检测血清CD4^(+)、CD8^(+)水平变化;qPCR检测CAG模型大鼠胃黏膜PD-1mRNA、PD-L1mRNA表达;Western-blot检测CAG模型大鼠胃黏膜组织PD-1、PD-L1蛋白表达.结果免疫组化结果示:与模型组和维酶素组比较,安胃汤高、低剂量组PD-L1表达均较低(P<0.01,P<0.05).ELISA实验结果示:与模型组比较,安胃汤高剂量组CD4^(+)表达及CD4^(+)/CD8^(+)比值升高(P<0.01,P<0.05),安胃汤各组和维酶素组CD8^(+)表达降低(P<0.01);与维酶素组比较,安胃汤高剂量组CD8^(+)表达降低(P<0.05).qPCR实验结果显示:与模型组比较,安胃汤高剂量组和维酶素组PD-1mRNA表达下降(P<0.01),安胃汤高、中剂量组PD-L1mRNA表达下降(P<0.01,P<0.05).Western-blot实验结果显示:与模型组比较,安胃汤高、中剂量组PD-1/Actin,PD-L1/Actin表达下降(P<0.01,P<0.05).结论安胃汤抗CAG作用可能与抑制PD-1/PD-L1信号通路诱导的细胞免疫逃逸有关.
基金Fund Project:National natural science foundation of China(No.81573915)。
文摘Objective:Doxorubicin is an efficient anthracycline drug for the treatment of tumor,however,its cardiotoxicity restricts the clinical application.Shenfu decoction has good clinical effect,but the pharmacological mechanism is not fully clarified.Method:The active components and potential targets of shenfu decoction were screened by TCMSP database,disease targets of doxorubicin-induced cardiotoxicity were collected by Genecards and OMIM database,and the network diagram of"drug-components-target-disease"was constructed by Cytoscape software.PPI network was constructed by STRING database.The target of action of the drug and the disease gene were mapped for GO and KEGG signal pathway analysis.Results:The study found that there are 52 main effective components of shenfu decoction,and 76 genes are involved in the potential therapeutic targets,among which 24 genes are potential targets of shenfu decoction in the treatment of doxorubicin-induced cardiotoxicity.The protein interaction network suggested that BCL2、BAX、CASP9、CASP3、MAPK8 may be the core target.GO enrichment analysis showed 52 cellular biological processes,and enrichment analysis of KEGG pathway revealed 99 involved signaling pathways,including TNF,apoptosis signaling pathways,etc.Conclusion:In this study,the network of"drug-components-target-disease"was constructed through network pharmacology,and it was found that the mechanism of"shenfu decoction"in the treatment of doxorubicin-induced cardiotoxicity involves multiple targets and pathways,which is conducive to guiding clinical medication.
基金Tan Xieyao and Zhang Huantian traditional Chinese medicine academic inheritance studio in Guangdong Provincial Hospital of TCM(No.E48807)Inheritance studio of Lingnan Cen’s miscellaneous diseases school in Guangdong Provincial Hospital of TCM(No.E43602)
文摘Objective:The purpose of this thesis is to explore the mechanism of ShenFu Decoction in the treatment of critically ill patients with COVID-19 based on network pharmacology.Methods:The primary active ingredients and potential targets of ShenFu Decoction were searched from the TCMSP database.The targets of COVID-19 were obtained by searching the GeneCards and OMIM databases.A ShenFu Decoction-compound-target-COVID19 network and a protein-protein interaction(PPI)network were respectively constructed through the Cytoscape 3.5.1 software and the STRING database.Gene Ontology(GO)function enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed via Bioconductor bioinformatics software package and R programming language.Results:ShenFu Decoction contains 255 compounds and 94 potential targets.43 primary active ingredients were searched from the TCMSP database with oral bioavailability(OB)≥30%and drug-likeness(DL)≥0.18 as the retrieval condition.Numbers of targets of COVID-19 were 352 by searching the GeneCards and the OMIM databases.16 key targets were acquired by intersecting the targets of drug with the targets of disease.There were 49 GO terms and 102 pathways after analyzing GO and KEGG.Conclusion:Kaempferol,ginsenoside rh2,beta-sitosterol,Stigmasterol and Deoxy andrographolide might be the main active ingredients which may cause the inhibition of the SARS-CoV-23CL hydrolase activity and regulate ACE2.As a result,the antiviral effect,immunoregulation,targeting cytokine storm of SFD may play an important role in the treatment of critically ill patients with COVID-19 through regulating multiple signaling pathways such as AGE-RAGE signaling pathway in diabetic complications,IL-17 signaling pathway,C-type lectin receptor signaling pathway,HIF-1 signaling pathway.
文摘目的观察参附汤联合同种异体NK细胞(alloreactive naturall killer cells,alloNK)对移植小鼠术后外周血象、骨髓有核细胞计数(nucleated cell counts,NCC)、骨髓造血组织容量(hematopoietic volume of bone marrow,HV)及骨髓病理的影响。方法BALB/c小鼠经过13.0 Gy剂量的全身照射(total body irradiation,TBI),4 h内经尾静脉注入供鼠骨髓单个核细胞(mononuclear cells,MNCs)8×10^(6)/kg,制作移植小鼠模型,然后随机分为模型组、alloNK组、参附汤组、参附+alloNK组4组,分别给予生理盐水、单用alloNK、单用参附汤和参附汤联合alloNK灌胃,观察治疗前及治疗后第7、14、30天,小鼠外周血象、骨髓NCC、HV及组织病理的变化。结果移植前及移植后第7天各组小鼠外周血象、骨髓NCC、HV无显著性差异。移植后第14天,模型组小鼠白细胞仍处于粒缺期,而单纯alloNK组和参附组小鼠的白细胞均有所上升,参附联合alloNK组小鼠上升幅度高于其他组。移植后第30天,模型组、alloNK组及参附组小鼠白细胞、骨髓NCC、HV均较前回升,但仍低于移植前水平,而参附联合alloNK组小鼠的白细胞、骨髓NCC、HV恢复至移植前水平,与其他组相比差异显著。结论参附汤可保护骨髓免受放射损伤、促进造血功能恢复、缩短粒细胞缺乏时间,而联合alloNK细胞促进造血功能恢复的作用更明显。
文摘目的观察补肾疏肝优化方治疗慢性乙型肝炎病毒(HBV)携带状态的临床疗效及对患者血清中程序性死亡受体1(PD-1)水平的影响。方法将86例慢性HBV携带状态患者随机分为治疗组和对照组,其中治疗组44例,对照组42例。治疗组给予补肾疏肝优化方治疗,对照组服用安慰剂,疗程为48周。观察两组患者治疗前后血清HBV DNA、e抗原(HBeAg)、表面抗原(HBsAg)、PD-1水平的变化及补肾疏肝优化方的临床疗效和安全性。结果试验过程中治疗组脱落1例,违背方案剔除3例,共纳入研究40例;对照组脱落2例,共纳入研究40例。治疗后,治疗组总有效率为32.50%(13/40),对照组总有效率为10.00%(4/40),治疗组总有效率明显高于对照组(P<0.05)。治疗后,治疗组患者的血清HBV DNA、HBeAg、HBsAg水平均较治疗前显著降低(P<0.05),且均低于对照组(P<0.05)。治疗后,治疗组HBeAg下降>0.5 lg、1 lg、2 lg COI的比例均高于对照组(P<0.05),治疗组HBeAg发生血清学转换的比例高于对照组,但差异无统计学意义(P>0.05)。治疗后,治疗组HBsAg下降>0.5 lg、1 lg COI的比例均高于对照组(P<0.05),治疗组HBsAg>2 lg COI的比例高于对照组,但差异无统计学意义(P>0.05)。治疗后,治疗组患者的血清PD-1水平较治疗前明显下降(P<0.05),且低于对照组(P<0.05)。两组患者治疗过程中安全性指标均未见明显异常。结论补肾疏肝优化方可在一定程度上降低慢性HBV携带状状态患者血清HBV DNA及病毒标志物水平,通过降低血清PD-1水平调节免疫,抑制HBV复制,疗效明显,安全性较好。
