Hyperexcitability of neural network is a key neurophysiological mechanism in several neurological disorders including epilepsy, neuropathic pain, and tinnitus. Although standard paradigm of pharmacological management ...Hyperexcitability of neural network is a key neurophysiological mechanism in several neurological disorders including epilepsy, neuropathic pain, and tinnitus. Although standard paradigm of pharmacological management of them is to suppress this hyperexcitability, such as having been exemplified by the use of certain antiepileptic drugs, their frequent refractoriness to drug treatment suggests likely different pathophysiological mechanism. Because the pathogenesis in these disorders exhibits a transition from an initial activity loss after injury or sensory deprivation to subsequent hyperexcitability and paroxysmal discharges, this process can be regarded as a process of functional compensation similar to homeostatic plasticity regulation, in which a set level of activity in neural network is maintained after injury-induced activity loss through enhanced network excitability. Enhancing brain activity, such as cortical stimulation that is found to be effective in relieving symptoms of these disorders, may reduce such hyperexcitability through homeostatic plasticity mechanism. Here we review current evidence of homeostatic plasticity in the mechanism of acquired epilepsy, neuropathic pain, and tinnitus and the effects and mechanism of cortical stimulation. Establishing a role of homeostatic plasticity in these disorders may provide a theoretical basis on their pathogenesis as well as guide the development and application of therapeutic approaches through electrically or pharmacologically stimulating brain activity for treating these disorders.展开更多
Objective To analyze the mechanism of action and compatibility of the active compounds of the traditional herb pair Bupleuri Radix(Chai Hu,CH,柴胡)-Paeoniae Radix Alba(Bai Shao,BS,白芍).Methods All chemical compounds ...Objective To analyze the mechanism of action and compatibility of the active compounds of the traditional herb pair Bupleuri Radix(Chai Hu,CH,柴胡)-Paeoniae Radix Alba(Bai Shao,BS,白芍).Methods All chemical compounds related to CH and BS were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Traditional Chinese Medicine Integrated Database(TCMID),Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine(Batman-TCM),Traditional Chinese Medicine Database@Taiwan(TCM Database@Taiwan),and the literature.Relevant compounds were screened for oral bioavailability(OB),drug-likeness(DL),and the Caco-2 cell model.The Uniprot,Genecard,and CTD databases were used to obtain information on potential targets and diseases of associated compounds.Based on this,Cytoscape 3.2.1 software,GO enrichment analysis,and KEGG pathway enrichment were used to analyze the potential mechanism of action and pathways of the CH-BS drug combination.Results A total of 23 active compounds of CH and BS were indentified after meeting specific criteria by network pharmacology,showing 79 predicted targets of active compounds.Among them,all targets were associated with 344 diseases,and the compounds in CH and BS were connected to 94 pathways and biological,such as calcium signaling pathway,neuroactive ligand-receptor interaction and TNF signaling pathway.Conclusions Our results preliminarily validated the main compounds in CH-BS herb pair interacted with multiple targets in different diseases,and the molecular mechanism of these compounds involves multiple pathways,thereby establishing a good foundation for further studies.展开更多
Objective To use systematic pharmacological strategies to explore the regulatory mechanisms of Ma Xing Shi Gan Decoction(MXSGD)against the coronavirus disease 2019(COVID-19).Methods Data on the compounds and targets o...Objective To use systematic pharmacological strategies to explore the regulatory mechanisms of Ma Xing Shi Gan Decoction(MXSGD)against the coronavirus disease 2019(COVID-19).Methods Data on the compounds and targets of MXSGD were collected from the Traditional Chinese Medicene Systems Parmacology Database and Analysis Platform(TCMSP)and TCM Databases@Taiwan.Data on ACE2-related targets and the protein-protein interaction(PPI)were collected from the String database.The Cytoscape 3.7.2 was used to construct and analyze the networks.The DAVID platform was used for Gene Ontology(GO)and pathway enrichment analyses.Results Data on 272 MXSGD targets and 21 SARS-CoV-2 potential targets were collected.Four networks were constructed and analyzed based on the data:(1)compound-target network of MXSGD;(2)MXSGD-SARS-CoV-2-PPI network;(3)cluster of MXSGD-SARS-CoV-2-PPI network;(4)Herb-Pathway-Target network.The core targets included AKT1,MAPK3,IL-6,TP53,VEGFA,TNF,CASP3,EGFR,EGF and MAPK1.The antiviral biological processes were inflammatory responses(inflammatory cells,inflammatory cytokines and their signaling pathways),immune responses(T cells,monocytes,B cells and other immune cells),immune factors(IFN-γ,TNF-αand so on),virus defense,humoral immunity and mucosal innate immune response.The antivirus-related signaling pathways included TNF,NOD-like receptor,FoxO,PI3K-AKT and Toll-like receptor signaling pathways.Conclusions MXSGD can control disease progression by regulating multiple compounds and targets;it can reduce inflammation and balance immunity by regulating several proteins that interact with ACE2 and signaling pathways closely related to disease development.展开更多
AIM: To explore the feasibility of local interleukin 2 (IL-2) in patients with different forms of abdominal cancer. This required experimentation with the time interval between IL-2 applications and the methods of ...AIM: To explore the feasibility of local interleukin 2 (IL-2) in patients with different forms of abdominal cancer. This required experimentation with the time interval between IL-2 applications and the methods of application. METHODS: Sixteen patients with stages Ⅲ and Ⅳ of gastrointestinal malignancies (primary or metastatic) who were admitted to our Department of Gastroenterology were treated with Iocoregionally applied IL-2 in low doses. RESULTS: No major problems applying Iocoregional IL-2 were encountered. In 6 out of 16 patients, a modest but clinically worthwhile improvement was obtained. Adverse effects were minimal. The therapeutic scheme was well tolerated, even in patients in a poor condition. CONCLUSION: This study demonstrates the feasibility of low dose Iocoregional IL-2 application in advanced abdominal cancer. Local IL-2 therapy gives only negligible adverse effects. The results suggest that it is important to apply intratumorally. Local IL-2 may be given adjunct to standard therapeutic regimes and does not imply complex surgical interventions. These initial results are encouraging.展开更多
Objective Our objective was to explore the action mechanism of the Jinyingzi(Rosae Laevigatae Fructus)–Qianshi(Euryales Semen)couplet herbs in the treatment of membranous nephropathy(MN)based on network pharmacology....Objective Our objective was to explore the action mechanism of the Jinyingzi(Rosae Laevigatae Fructus)–Qianshi(Euryales Semen)couplet herbs in the treatment of membranous nephropathy(MN)based on network pharmacology.Methods The active ingredients and targets of Jinyingzi(Rosae Laevigatae Fructus)and Qianshi(Euryales Semen)were screened by systematic pharmacology database and analysis platform.Online Human Mendelian Genetic database and GeneCards database were used to retrieve MN-related targets.The active ingredient-related targets and MN disease targets were introduced into Venny 2.1,and Wayne diagram was drawn.The intersection targets were the potential targets of the Jinyingzi(Rosae Laevigatae Fructus)–Qianshi(Euryales Semen)couplet herbs in the treatment of MN.The protein interaction network of potential targets was constructed,and the core targets were screened with String platform.Metascape platform was used for functional enrichment analysis of gene ontology(GO)and pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG).The“herb-active ingredient-target-pathway”networks were drawn by using Cytoscape software,and the key components,targets,and signaling pathways were screened.Results A total of 8 active ingredients and 193 related targets in Jinyingzi(Rosae Laevigatae Fructus)and Qianshi(Euryales Semen)were screened out;a total of 1,621 targets of MN disease and 105 potential targets for the treatment of MN were obtained in the treatment with Jinyingzi(Rosae Laevigatae Fructus)–Qianshi(Euryales Semen)couplet herbs;40 core targets were screened by protein–protein interaction network topology analysis;a total of 1,978 results were obtained by GO function enrichment analysis,and 206 signal pathways were obtained by KEGG pathway enrichment analysis and screening.The network topology analysis of“herb-active ingredient-target-pathway”showed that the key components included quercetin,kaempferol,β-sitosterol,etc.;the key targets included protein kinase Bα(AKT),mitogen-activated protein kinase 1(MAPK1),B-cell lymphoma-2(BCL2),prostaglandin-endoperoxide synthase 2(PTGS2),etc.;the key pathways included advanced glycation end product/receptor of AGE signaling pathway,phosphatidyl inositol 3-kinase(PI3K)/AKT signaling pathway,MAPK signaling pathway,hypoxia-inducible factor-1 signaling pathway,Ras signaling pathway,nuclear factor kappa-B(NF-κB)signaling pathway,Toll-like receptors signaling pathway,p53 signaling pathway and vascular endothelial growth factor signaling pathway in the late stage of diabetic complications.Conclusion The Jinyingzi(Rosae Laevigatae Fructus)–Qianshi(Euryales Semen)couplet herbs can regulate PI3K/AKT,MAPK,NF-κB signaling pathways in MN by targeting proteins of AKT1,MAPK8,PTGS2 through key components of quercetin,β-sitosterol,and kaempferol,so as to inhibit the overexpression of inflammatory factors in renal tissues,regulate inflammatory response,and improve renal function.展开更多
ObjectiveThe aim of the study is to explore the molecular mechanism of Yadanzi(Brucea javanica)in the treatment of glioblastoma(GBM)by using the methods of bioinformatics and network pharmacology.Methods The Tradition...ObjectiveThe aim of the study is to explore the molecular mechanism of Yadanzi(Brucea javanica)in the treatment of glioblastoma(GBM)by using the methods of bioinformatics and network pharmacology.Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and literature retrieval method were applied to obtain the active ingredients of Yadanzi(Brucea javanica),and to predict the relevant targets of the active ingredients.The GBM-related targets were retrieved and screened through the Gene Expression Profling Interactive Analysis(GEPIA)database,and mapped to each other with the targets of the components of Yadanzi(Brucea javanica)to obtain the intersection targets.The GBM differentially expressed gene targets were imported into the String database to obtain the protein interaction relationship,the Cytoscape software was used to draw the protein interaction network,the Cytobba and MCODE plug-ins were used to screen the core genes and important protein interaction modules,and the GEPIA database was applied to make survival analysis of the core genes.The network map of“active ingredients-targets”was constructed through the Cytoscape 3.6.1 software.Gene Ontology(GO)biological function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis for GBM differentially expressed genes were performed through the DAVID database.ResultsThrough TCMSP and literature retrieval,23 potential active ingredients and 129 related targets were obtained from Yadanzi(Brucea javanica).In the GEPIA database,247 GBM differentially expressed genes were screened,including 113 upregulated genes and 134 downregulated genes.After mapping with the targets related to the active ingredients of Yadanzi(Brucea javanica),six intersection targets were obtained,that is,the potential action targets of Yadanzi(Brucea javanica)in treating GBM,including MMP2,HMOX1,BIRC5,EGFR,CCNB2,and TOP2A.Cytoscape software was applied to build an“active ingredient-action target”network.Two active ingredients and five action targets of β-sitosterol(BS)and luteolin were found,and the targets were mainly concentrated in BS.It was found by KEGG pathway enrichment analysis that GBM differentially expressed genes were mainly involved in signaling pathways related to Staphylococcus aureus infection,phagosome formation,tuberculosis and systemic lupus erythematosus and other infectious and autoimmune diseases.It was found by GO enrichment analysis that the GBM differentially expressed genes mainly involved such biological processes(BP)as the processing and presentation of exogenous antigenic peptides and polysaccharide antigens through MHC Il molecules,y-interferon-mediated signaling pathways,extracellular matrix composition,and chemical synapses transmission;it involved cellular components such as cell junctions,axon terminal buttons,extracellular space,vesicle membranes for endocytosis,and MHC Il protein complexes;molecular functions such as calcium-mediated ionic protein binding,MHC Il molecular receptor activity,immunoglobulin binding,and phospholipase inhibitor activity were also involved.Survival analysis was conducted by GEPIA on the top 37 core targets in degree value,and a total of five genes related to GBM prognosis were obtained.Among them,FN1 and MMP2 were highly expressed while GABRD(v-aminobutyric acid A receptor delta subunit),RBFOX1,and SLC6A7 were expressed at a low level in cancer patients.Conclusion The pathogenesis of GBM is closely related to the human immune system,and BS and luteolin may be the main material basis of Yadanzi(Brucea javanica)for the treatment of GBM and the improvement of prognosis.The molecular mechanism may be related to the physical barrier formed by destroying the tumor cell stromal 68 Treatment of Glioblastoma Based on Bioinformatics and Network Pharmacology Zhao,Si.molecules and its involvement in tumor immune response.展开更多
Objective:To explore the targels and molecular mechanism of Gancao Yangyin Decoction(甘草养阴汤,GCYYD)based on network pharmacology.Methods:The effective chemical components of 7 kinds of Chinese materia medica in GCY...Objective:To explore the targels and molecular mechanism of Gancao Yangyin Decoction(甘草养阴汤,GCYYD)based on network pharmacology.Methods:The effective chemical components of 7 kinds of Chinese materia medica in GCYYD and their relevant targets were obtai ned through the traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)and the encyelopedia of traditional Chinese medicine(ETCM).The aging-related targets were obtained through GeneCards database.The targets related to the effective chemical components were mapped with the aging-related targets,and the gene targets of GCY YD for intervening in aging were obtained.The protein interaction network diagram of GCY YD interfering with aging was drawn through String database and Cytoscape 3.7.1 software,and the core target genes were screened.The potential targets obtained were analyzed by gene ontology(GO)biological function enrichment analysis and kyoto encyelopedia of genes and genomes(KEGG)pathway enrichment analysis.Results:Totally 130 effective chemical components of the 7 kinds of Chinese materia medica of GCYYD and 276 related targets were obtained from TCMSP and ETCM databases.Totally 216 aging-related targets were obtained through GeneCards database.There were 63 target genes intervening in aging in GCYYD,with core target genes ALB,AKTI,TNF,L 6,MMP-3,VEGFA,CASP5,etc.Through biological function and signaling pathway enrichment analyses for the target genes with R software,147 KEGG signaling pathways were found,mainly related to age-RAGE signaling pathway in diabetic complications,proteoglycans in cancer,fluid shear stress and atherosclero-sis,HIF-1 signaling pathway,human cytomegalovirus infection,celluar senescence,prostate cancer,bladder cancer,elte.Conclusion:GCYYD can intervene in aging through"multicomponents-mulitargets-multipath-ways",which lays foundation for further experimental research.展开更多
Objective: Excavate the medication rule of traditional Chinese medicine in the treatment of prostate cancer, and predicting the biomolecular level mechanism of high-frequency drug compatibility. Methods: Relevant docu...Objective: Excavate the medication rule of traditional Chinese medicine in the treatment of prostate cancer, and predicting the biomolecular level mechanism of high-frequency drug compatibility. Methods: Relevant documents in CNKI, Wanfang Medical Network and VIP Chinese Biomedical Periodical Database Pubmed, EMbase were collected and collated systematically. Frequency statistics, association rule analysis and new party mining were carried out using TCMISSV2.5. BATMAN-TCM was used to analyze the interaction relationship and related pathways between high-frequency drug targets. Results: Huangqi (Astragalus membranaceus) was the single drug most used of the 102prescriptions included in the standard. There are 6 pairs of combinations with high confidence in association rule analysis. System entropy cluster analysis resulted in 20 core drug combinations and 9 new prescriptions. Through KEGG pathway analysis of Huangqi, Fuling (Poria cocos), Gancao (Glycyrrhiza uralensis) and Dihuang (Rehmannia glutinosa), it was found that the number of potential targets of the neural active ligand receptor rented pathway and purine metabolism pathway was the largest. Conclusions: Prostate cancer is mainly treated with deficiency-tonifying drugs, which are combined with drugs for promoting blood circulation, removing blood stasis, clearing heat, promoting diuresis, detoxifying and resolving hard mass. The mechanism of action of high-frequency traditional Chinese medicine may be realized by interfering with the neuroactive ligand receptor interaction pathway and purine metabolism pathway.展开更多
Objective: To imensify management on high-alert Medications, ensure clinical medication safety. Methods: Statistical analysis was applied between before and after the implementation of PDCA-cycle in the management o...Objective: To imensify management on high-alert Medications, ensure clinical medication safety. Methods: Statistical analysis was applied between before and after the implementation of PDCA-cycle in the management of high-alert Medications. Results: After PDCA- cycle, the rate of management of high-alert Medications increased from 59.5% to 94.6% (P〈0.01), Conclusion: Our study suggested that the PDCA-cycle play an important role in the management of high-alert Medications, and then can increase the level of safety on management and utilization of medicine.展开更多
Objective Our objective was to investigate the potential mechanism of action of Qihuang Jiangtang capsule(QHJTC)in the treatment of type 2 diabetes mellitus(T2DM)through network pharmacology and molecular docking.Meth...Objective Our objective was to investigate the potential mechanism of action of Qihuang Jiangtang capsule(QHJTC)in the treatment of type 2 diabetes mellitus(T2DM)through network pharmacology and molecular docking.Methods The active components of materia medica in the formula of QHJTC were searched on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Encyclopedia of Traditional Chinese Medicine.The targets related to the active components were obtained via PubChem database.The targets related to T2DM were retrieved through the GeneCards database.The targets corresponding to the active components and diabetes mellitus were uploaded to the Venn diagrams website to get the Venn diagram,and the intersecting targets were the potential targets of QHJTC in treating T2DM.The active components and potential targets were imported into Cytoscape 3.7.2 software to construct the active component–potential target network,and the key compounds and targets were screened by the Network Analyzer module in the Tools module.The potential targets were imported into the STRING database to obtain the interaction relationships,so as to analyze and construct the protein–protein interaction(PPI)network by Cytoscape 3.7.2 software.The intersecting targets were introduced into Metascape for gene ontology(GO)functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The top 20 signaling pathways obtained by the KEGG pathway enrichment analysis and the related targets and the corresponding targets were analyzed by using Cytoscape 3.7.2 software to construct the“active component–important target-key pathway network”for the intervention of T2DM with QHJTC.The molecular docking of active components and core targets was performed with AutoDock software.Results A total of 237 active components and 281 related targets were obtained from QHJTC,as well as 1362 T2DM targets and 155 potential targets of QHJTC in treating T2DM.There were 32 key components and 49 key targets identified by the active component–potential target network topology analysis.There were 471 terms obtained from GO functional enrichment analysis,among which 248 related to biological processes,125 related to molecular functions,and 98 related to cellular components.There were 299 signaling pathways obtained from KEGG pathway enrichment analysis.The active components of QHJTC were found spontaneously binding to the core targets.Conclusions QHJTC can treat T2DM through multi-components,multi-targets,and multi-pathways.展开更多
Irrational use of medicines is a major problem worldwide, and it is believed there would be positive correlation between the National Essential Medicines Policies(NEMPs) and the level of rational use of medicines(RUMs...Irrational use of medicines is a major problem worldwide, and it is believed there would be positive correlation between the National Essential Medicines Policies(NEMPs) and the level of rational use of medicines(RUMs). Though there is some early evidence on the NEMPs’ effects on RUMs in China, the evidence is scarce, and conclusions vary. In the present study, we aimed to evaluate the impacts of the NEMPs of China on the RUMs in the primary health care institutions(PHCs). A cross-sectional survey was conducted in 2010. A total of 201 PHCs from six provinces of China were selected, and 39 181 prescriptions were extracted from January to June, 2010. Six indicators were used and tested by independent-samples T test. We found that the average number of drugs per prescription in PHCs with NEMP implementation(the treatment group) was significantly higher than that of the group without NEMP implementation(the control group)(3.37 vs. 2.83, P<0.01). There was no significant difference in the average cost per prescription(81.43 vs. 75.02). The percentage of prescriptions, including an antibiotic(53.40% vs. 36.48%, P<0.01) or an injection(40.54% vs. 27.94%, P<0.01), was higher in the treatment group, and the percentage of drugs prescribed by general name was significantly lower(83.71% vs. 93.11%, P<0.01). For the percentage of drugs prescribed from essential medicines list, the treatment group exhibited the higher ratio(76.12% vs. 53.45%, P<0.01). From this study, the NEMPs were not likely to have a positive impact on RUMs. China still needed efforts to improve the selection, the absence of physicians’ active involvement, and the patients’ habits of irrational medication use.展开更多
基金supported in part by the NIH DA039530(to XJ)a grant from the CURE Epilepsy Foundation(to XJ)
文摘Hyperexcitability of neural network is a key neurophysiological mechanism in several neurological disorders including epilepsy, neuropathic pain, and tinnitus. Although standard paradigm of pharmacological management of them is to suppress this hyperexcitability, such as having been exemplified by the use of certain antiepileptic drugs, their frequent refractoriness to drug treatment suggests likely different pathophysiological mechanism. Because the pathogenesis in these disorders exhibits a transition from an initial activity loss after injury or sensory deprivation to subsequent hyperexcitability and paroxysmal discharges, this process can be regarded as a process of functional compensation similar to homeostatic plasticity regulation, in which a set level of activity in neural network is maintained after injury-induced activity loss through enhanced network excitability. Enhancing brain activity, such as cortical stimulation that is found to be effective in relieving symptoms of these disorders, may reduce such hyperexcitability through homeostatic plasticity mechanism. Here we review current evidence of homeostatic plasticity in the mechanism of acquired epilepsy, neuropathic pain, and tinnitus and the effects and mechanism of cortical stimulation. Establishing a role of homeostatic plasticity in these disorders may provide a theoretical basis on their pathogenesis as well as guide the development and application of therapeutic approaches through electrically or pharmacologically stimulating brain activity for treating these disorders.
基金funding support from the the National Natural Science Foundation of China (No. 81573780)High-level Hospital Construction (No. 211010010120)
文摘Objective To analyze the mechanism of action and compatibility of the active compounds of the traditional herb pair Bupleuri Radix(Chai Hu,CH,柴胡)-Paeoniae Radix Alba(Bai Shao,BS,白芍).Methods All chemical compounds related to CH and BS were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Traditional Chinese Medicine Integrated Database(TCMID),Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine(Batman-TCM),Traditional Chinese Medicine Database@Taiwan(TCM Database@Taiwan),and the literature.Relevant compounds were screened for oral bioavailability(OB),drug-likeness(DL),and the Caco-2 cell model.The Uniprot,Genecard,and CTD databases were used to obtain information on potential targets and diseases of associated compounds.Based on this,Cytoscape 3.2.1 software,GO enrichment analysis,and KEGG pathway enrichment were used to analyze the potential mechanism of action and pathways of the CH-BS drug combination.Results A total of 23 active compounds of CH and BS were indentified after meeting specific criteria by network pharmacology,showing 79 predicted targets of active compounds.Among them,all targets were associated with 344 diseases,and the compounds in CH and BS were connected to 94 pathways and biological,such as calcium signaling pathway,neuroactive ligand-receptor interaction and TNF signaling pathway.Conclusions Our results preliminarily validated the main compounds in CH-BS herb pair interacted with multiple targets in different diseases,and the molecular mechanism of these compounds involves multiple pathways,thereby establishing a good foundation for further studies.
基金the funding support from the National Natural Science Foundation of China(No.81774126,No.81973670)the Natural Science Foundation of Hunan Province(No.2016JJ2095,No.2017JJ3232)+2 种基金Scientific Research Project of Traditional Chinese Medicine for the Prevention and Treatment of New Pneumonia in Hunan Province(No.GYGG007)the Construction Project of Specialty of Traditional Chinese Medicine in Guangdong Provincethe Construction Project of Specialty of Traditional Chinese Medicine in Shenzhen。
文摘Objective To use systematic pharmacological strategies to explore the regulatory mechanisms of Ma Xing Shi Gan Decoction(MXSGD)against the coronavirus disease 2019(COVID-19).Methods Data on the compounds and targets of MXSGD were collected from the Traditional Chinese Medicene Systems Parmacology Database and Analysis Platform(TCMSP)and TCM Databases@Taiwan.Data on ACE2-related targets and the protein-protein interaction(PPI)were collected from the String database.The Cytoscape 3.7.2 was used to construct and analyze the networks.The DAVID platform was used for Gene Ontology(GO)and pathway enrichment analyses.Results Data on 272 MXSGD targets and 21 SARS-CoV-2 potential targets were collected.Four networks were constructed and analyzed based on the data:(1)compound-target network of MXSGD;(2)MXSGD-SARS-CoV-2-PPI network;(3)cluster of MXSGD-SARS-CoV-2-PPI network;(4)Herb-Pathway-Target network.The core targets included AKT1,MAPK3,IL-6,TP53,VEGFA,TNF,CASP3,EGFR,EGF and MAPK1.The antiviral biological processes were inflammatory responses(inflammatory cells,inflammatory cytokines and their signaling pathways),immune responses(T cells,monocytes,B cells and other immune cells),immune factors(IFN-γ,TNF-αand so on),virus defense,humoral immunity and mucosal innate immune response.The antivirus-related signaling pathways included TNF,NOD-like receptor,FoxO,PI3K-AKT and Toll-like receptor signaling pathways.Conclusions MXSGD can control disease progression by regulating multiple compounds and targets;it can reduce inflammation and balance immunity by regulating several proteins that interact with ACE2 and signaling pathways closely related to disease development.
文摘AIM: To explore the feasibility of local interleukin 2 (IL-2) in patients with different forms of abdominal cancer. This required experimentation with the time interval between IL-2 applications and the methods of application. METHODS: Sixteen patients with stages Ⅲ and Ⅳ of gastrointestinal malignancies (primary or metastatic) who were admitted to our Department of Gastroenterology were treated with Iocoregionally applied IL-2 in low doses. RESULTS: No major problems applying Iocoregional IL-2 were encountered. In 6 out of 16 patients, a modest but clinically worthwhile improvement was obtained. Adverse effects were minimal. The therapeutic scheme was well tolerated, even in patients in a poor condition. CONCLUSION: This study demonstrates the feasibility of low dose Iocoregional IL-2 application in advanced abdominal cancer. Local IL-2 therapy gives only negligible adverse effects. The results suggest that it is important to apply intratumorally. Local IL-2 may be given adjunct to standard therapeutic regimes and does not imply complex surgical interventions. These initial results are encouraging.
基金Shaanxi Key R&D Program Project(2018ZDXM-SF-011).
文摘Objective Our objective was to explore the action mechanism of the Jinyingzi(Rosae Laevigatae Fructus)–Qianshi(Euryales Semen)couplet herbs in the treatment of membranous nephropathy(MN)based on network pharmacology.Methods The active ingredients and targets of Jinyingzi(Rosae Laevigatae Fructus)and Qianshi(Euryales Semen)were screened by systematic pharmacology database and analysis platform.Online Human Mendelian Genetic database and GeneCards database were used to retrieve MN-related targets.The active ingredient-related targets and MN disease targets were introduced into Venny 2.1,and Wayne diagram was drawn.The intersection targets were the potential targets of the Jinyingzi(Rosae Laevigatae Fructus)–Qianshi(Euryales Semen)couplet herbs in the treatment of MN.The protein interaction network of potential targets was constructed,and the core targets were screened with String platform.Metascape platform was used for functional enrichment analysis of gene ontology(GO)and pathway enrichment analysis of Kyoto Encyclopedia of Genes and Genomes(KEGG).The“herb-active ingredient-target-pathway”networks were drawn by using Cytoscape software,and the key components,targets,and signaling pathways were screened.Results A total of 8 active ingredients and 193 related targets in Jinyingzi(Rosae Laevigatae Fructus)and Qianshi(Euryales Semen)were screened out;a total of 1,621 targets of MN disease and 105 potential targets for the treatment of MN were obtained in the treatment with Jinyingzi(Rosae Laevigatae Fructus)–Qianshi(Euryales Semen)couplet herbs;40 core targets were screened by protein–protein interaction network topology analysis;a total of 1,978 results were obtained by GO function enrichment analysis,and 206 signal pathways were obtained by KEGG pathway enrichment analysis and screening.The network topology analysis of“herb-active ingredient-target-pathway”showed that the key components included quercetin,kaempferol,β-sitosterol,etc.;the key targets included protein kinase Bα(AKT),mitogen-activated protein kinase 1(MAPK1),B-cell lymphoma-2(BCL2),prostaglandin-endoperoxide synthase 2(PTGS2),etc.;the key pathways included advanced glycation end product/receptor of AGE signaling pathway,phosphatidyl inositol 3-kinase(PI3K)/AKT signaling pathway,MAPK signaling pathway,hypoxia-inducible factor-1 signaling pathway,Ras signaling pathway,nuclear factor kappa-B(NF-κB)signaling pathway,Toll-like receptors signaling pathway,p53 signaling pathway and vascular endothelial growth factor signaling pathway in the late stage of diabetic complications.Conclusion The Jinyingzi(Rosae Laevigatae Fructus)–Qianshi(Euryales Semen)couplet herbs can regulate PI3K/AKT,MAPK,NF-κB signaling pathways in MN by targeting proteins of AKT1,MAPK8,PTGS2 through key components of quercetin,β-sitosterol,and kaempferol,so as to inhibit the overexpression of inflammatory factors in renal tissues,regulate inflammatory response,and improve renal function.
文摘ObjectiveThe aim of the study is to explore the molecular mechanism of Yadanzi(Brucea javanica)in the treatment of glioblastoma(GBM)by using the methods of bioinformatics and network pharmacology.Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and literature retrieval method were applied to obtain the active ingredients of Yadanzi(Brucea javanica),and to predict the relevant targets of the active ingredients.The GBM-related targets were retrieved and screened through the Gene Expression Profling Interactive Analysis(GEPIA)database,and mapped to each other with the targets of the components of Yadanzi(Brucea javanica)to obtain the intersection targets.The GBM differentially expressed gene targets were imported into the String database to obtain the protein interaction relationship,the Cytoscape software was used to draw the protein interaction network,the Cytobba and MCODE plug-ins were used to screen the core genes and important protein interaction modules,and the GEPIA database was applied to make survival analysis of the core genes.The network map of“active ingredients-targets”was constructed through the Cytoscape 3.6.1 software.Gene Ontology(GO)biological function enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway enrichment analysis for GBM differentially expressed genes were performed through the DAVID database.ResultsThrough TCMSP and literature retrieval,23 potential active ingredients and 129 related targets were obtained from Yadanzi(Brucea javanica).In the GEPIA database,247 GBM differentially expressed genes were screened,including 113 upregulated genes and 134 downregulated genes.After mapping with the targets related to the active ingredients of Yadanzi(Brucea javanica),six intersection targets were obtained,that is,the potential action targets of Yadanzi(Brucea javanica)in treating GBM,including MMP2,HMOX1,BIRC5,EGFR,CCNB2,and TOP2A.Cytoscape software was applied to build an“active ingredient-action target”network.Two active ingredients and five action targets of β-sitosterol(BS)and luteolin were found,and the targets were mainly concentrated in BS.It was found by KEGG pathway enrichment analysis that GBM differentially expressed genes were mainly involved in signaling pathways related to Staphylococcus aureus infection,phagosome formation,tuberculosis and systemic lupus erythematosus and other infectious and autoimmune diseases.It was found by GO enrichment analysis that the GBM differentially expressed genes mainly involved such biological processes(BP)as the processing and presentation of exogenous antigenic peptides and polysaccharide antigens through MHC Il molecules,y-interferon-mediated signaling pathways,extracellular matrix composition,and chemical synapses transmission;it involved cellular components such as cell junctions,axon terminal buttons,extracellular space,vesicle membranes for endocytosis,and MHC Il protein complexes;molecular functions such as calcium-mediated ionic protein binding,MHC Il molecular receptor activity,immunoglobulin binding,and phospholipase inhibitor activity were also involved.Survival analysis was conducted by GEPIA on the top 37 core targets in degree value,and a total of five genes related to GBM prognosis were obtained.Among them,FN1 and MMP2 were highly expressed while GABRD(v-aminobutyric acid A receptor delta subunit),RBFOX1,and SLC6A7 were expressed at a low level in cancer patients.Conclusion The pathogenesis of GBM is closely related to the human immune system,and BS and luteolin may be the main material basis of Yadanzi(Brucea javanica)for the treatment of GBM and the improvement of prognosis.The molecular mechanism may be related to the physical barrier formed by destroying the tumor cell stromal 68 Treatment of Glioblastoma Based on Bioinformatics and Network Pharmacology Zhao,Si.molecules and its involvement in tumor immune response.
基金We thank for the funding support from the General Project of the National Natural Science Foundation of China(8197060898)。
文摘Objective:To explore the targels and molecular mechanism of Gancao Yangyin Decoction(甘草养阴汤,GCYYD)based on network pharmacology.Methods:The effective chemical components of 7 kinds of Chinese materia medica in GCYYD and their relevant targets were obtai ned through the traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)and the encyelopedia of traditional Chinese medicine(ETCM).The aging-related targets were obtained through GeneCards database.The targets related to the effective chemical components were mapped with the aging-related targets,and the gene targets of GCY YD for intervening in aging were obtained.The protein interaction network diagram of GCY YD interfering with aging was drawn through String database and Cytoscape 3.7.1 software,and the core target genes were screened.The potential targets obtained were analyzed by gene ontology(GO)biological function enrichment analysis and kyoto encyelopedia of genes and genomes(KEGG)pathway enrichment analysis.Results:Totally 130 effective chemical components of the 7 kinds of Chinese materia medica of GCYYD and 276 related targets were obtained from TCMSP and ETCM databases.Totally 216 aging-related targets were obtained through GeneCards database.There were 63 target genes intervening in aging in GCYYD,with core target genes ALB,AKTI,TNF,L 6,MMP-3,VEGFA,CASP5,etc.Through biological function and signaling pathway enrichment analyses for the target genes with R software,147 KEGG signaling pathways were found,mainly related to age-RAGE signaling pathway in diabetic complications,proteoglycans in cancer,fluid shear stress and atherosclero-sis,HIF-1 signaling pathway,human cytomegalovirus infection,celluar senescence,prostate cancer,bladder cancer,elte.Conclusion:GCYYD can intervene in aging through"multicomponents-mulitargets-multipath-ways",which lays foundation for further experimental research.
基金the National Natural Science Foundation of Hebei (No.H2018201179)Hebei University of Science and Technology (No. QN2016077)Health and Family Planning Commission of Hebei (No. 20160388).
文摘Objective: Excavate the medication rule of traditional Chinese medicine in the treatment of prostate cancer, and predicting the biomolecular level mechanism of high-frequency drug compatibility. Methods: Relevant documents in CNKI, Wanfang Medical Network and VIP Chinese Biomedical Periodical Database Pubmed, EMbase were collected and collated systematically. Frequency statistics, association rule analysis and new party mining were carried out using TCMISSV2.5. BATMAN-TCM was used to analyze the interaction relationship and related pathways between high-frequency drug targets. Results: Huangqi (Astragalus membranaceus) was the single drug most used of the 102prescriptions included in the standard. There are 6 pairs of combinations with high confidence in association rule analysis. System entropy cluster analysis resulted in 20 core drug combinations and 9 new prescriptions. Through KEGG pathway analysis of Huangqi, Fuling (Poria cocos), Gancao (Glycyrrhiza uralensis) and Dihuang (Rehmannia glutinosa), it was found that the number of potential targets of the neural active ligand receptor rented pathway and purine metabolism pathway was the largest. Conclusions: Prostate cancer is mainly treated with deficiency-tonifying drugs, which are combined with drugs for promoting blood circulation, removing blood stasis, clearing heat, promoting diuresis, detoxifying and resolving hard mass. The mechanism of action of high-frequency traditional Chinese medicine may be realized by interfering with the neuroactive ligand receptor interaction pathway and purine metabolism pathway.
文摘Objective: To imensify management on high-alert Medications, ensure clinical medication safety. Methods: Statistical analysis was applied between before and after the implementation of PDCA-cycle in the management of high-alert Medications. Results: After PDCA- cycle, the rate of management of high-alert Medications increased from 59.5% to 94.6% (P〈0.01), Conclusion: Our study suggested that the PDCA-cycle play an important role in the management of high-alert Medications, and then can increase the level of safety on management and utilization of medicine.
基金supported by the National Natural Science Foundation of China(82074584)the National Key Innovative Talents Training Project Of Traditional Chinese Medicine(2019-128).
文摘Objective Our objective was to investigate the potential mechanism of action of Qihuang Jiangtang capsule(QHJTC)in the treatment of type 2 diabetes mellitus(T2DM)through network pharmacology and molecular docking.Methods The active components of materia medica in the formula of QHJTC were searched on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and Encyclopedia of Traditional Chinese Medicine.The targets related to the active components were obtained via PubChem database.The targets related to T2DM were retrieved through the GeneCards database.The targets corresponding to the active components and diabetes mellitus were uploaded to the Venn diagrams website to get the Venn diagram,and the intersecting targets were the potential targets of QHJTC in treating T2DM.The active components and potential targets were imported into Cytoscape 3.7.2 software to construct the active component–potential target network,and the key compounds and targets were screened by the Network Analyzer module in the Tools module.The potential targets were imported into the STRING database to obtain the interaction relationships,so as to analyze and construct the protein–protein interaction(PPI)network by Cytoscape 3.7.2 software.The intersecting targets were introduced into Metascape for gene ontology(GO)functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis.The top 20 signaling pathways obtained by the KEGG pathway enrichment analysis and the related targets and the corresponding targets were analyzed by using Cytoscape 3.7.2 software to construct the“active component–important target-key pathway network”for the intervention of T2DM with QHJTC.The molecular docking of active components and core targets was performed with AutoDock software.Results A total of 237 active components and 281 related targets were obtained from QHJTC,as well as 1362 T2DM targets and 155 potential targets of QHJTC in treating T2DM.There were 32 key components and 49 key targets identified by the active component–potential target network topology analysis.There were 471 terms obtained from GO functional enrichment analysis,among which 248 related to biological processes,125 related to molecular functions,and 98 related to cellular components.There were 299 signaling pathways obtained from KEGG pathway enrichment analysis.The active components of QHJTC were found spontaneously binding to the core targets.Conclusions QHJTC can treat T2DM through multi-components,multi-targets,and multi-pathways.
基金National Natural Science Foundation of China(Grant No.71303011,71774005)
文摘Irrational use of medicines is a major problem worldwide, and it is believed there would be positive correlation between the National Essential Medicines Policies(NEMPs) and the level of rational use of medicines(RUMs). Though there is some early evidence on the NEMPs’ effects on RUMs in China, the evidence is scarce, and conclusions vary. In the present study, we aimed to evaluate the impacts of the NEMPs of China on the RUMs in the primary health care institutions(PHCs). A cross-sectional survey was conducted in 2010. A total of 201 PHCs from six provinces of China were selected, and 39 181 prescriptions were extracted from January to June, 2010. Six indicators were used and tested by independent-samples T test. We found that the average number of drugs per prescription in PHCs with NEMP implementation(the treatment group) was significantly higher than that of the group without NEMP implementation(the control group)(3.37 vs. 2.83, P<0.01). There was no significant difference in the average cost per prescription(81.43 vs. 75.02). The percentage of prescriptions, including an antibiotic(53.40% vs. 36.48%, P<0.01) or an injection(40.54% vs. 27.94%, P<0.01), was higher in the treatment group, and the percentage of drugs prescribed by general name was significantly lower(83.71% vs. 93.11%, P<0.01). For the percentage of drugs prescribed from essential medicines list, the treatment group exhibited the higher ratio(76.12% vs. 53.45%, P<0.01). From this study, the NEMPs were not likely to have a positive impact on RUMs. China still needed efforts to improve the selection, the absence of physicians’ active involvement, and the patients’ habits of irrational medication use.