Silver in the form of AgNO3 was added to ZnO-based varistor ceramics prepared by the solid-state reaction method.The effects of AgNO3 on both the microstructure and electrical properties of the varistors were studied ...Silver in the form of AgNO3 was added to ZnO-based varistor ceramics prepared by the solid-state reaction method.The effects of AgNO3 on both the microstructure and electrical properties of the varistors were studied in detail.The optimum addition amount of AgNO3 in ZnO-based varistors was also determined.The mechanism for grain growth inhibition by silver doping was also proposed.The results indicate that the varistor threshold voltage increases substantially along with the AgNO3 content increasing from 0 to 1.5mol%.Also,the introduction of AgNO3 can depress the mean grain size of ZnO,which is mainly responsible for the threshold voltage.Furthermore,the addition of AgNO3 results in a slight decrease of donor density and a more severe fall in the density of interface states,which cause a decline in barrier height and an increase in the depletion layer.展开更多
NG-CT-10 and NG-CT-20 are newly developed grades of nuclear-grade graphite from China.In this study,their oxidation behaviors were experimentally investigated using thermal gravimetric analysis.Microstructural evoluti...NG-CT-10 and NG-CT-20 are newly developed grades of nuclear-grade graphite from China.In this study,their oxidation behaviors were experimentally investigated using thermal gravimetric analysis.Microstructural evolution before and after oxidation was investigated using scanning electron microscope,mercury intrusion,and Raman spectroscopy.The apparent activation energy of NG-CT-10 nuclear graphite is 161.4 kJ/mol in a reaction temperature range of 550–700℃and that of NG-CT-20 is 153.5 kJ/mol in a temperature range of 550–650℃.The activation energy in the inner diffusion control regime is approximately half that in the kinetics control regime.At high temperatures,the binder phase is preferentially oxidized over the filler particles and small pores are generated in the binder.No new large or deep pores are generated on the graphite surfaces.Oxygen can diffuse along the boundaries of filler particles and through the binder phase,but cannot diffuse into the spaces between the nanocrystallites in the filler particles.Filler particles are oxidized starting at their outer surfaces,and the sizes of nanocrystallites do not decrease following oxidation.展开更多
Objective:To explore the protective effects of anthrahydroquinone-2,6-disulfonate(AH_(2)QDS)on the kidneys of paraquat(PQ)poisoned rats via the apelin-APJ pathway.Methods:Male Sprague Dawley rats were divided into fou...Objective:To explore the protective effects of anthrahydroquinone-2,6-disulfonate(AH_(2)QDS)on the kidneys of paraquat(PQ)poisoned rats via the apelin-APJ pathway.Methods:Male Sprague Dawley rats were divided into four experimental groups:control,PQ,PQ+sivelestat,and PQ+AH_(2)QDS.The PQ+sivelestat group served as the positive control group.The model of poisoning was established via intragastric treatment with a 20%PQ pesticide solution at 200 mg/kg.Two hours after poisoning,the PQ+sivelestat group was treated with sivelestat,while the PQ+AH_(2)QDS group was given AH_(2)QDS.Six rats were selected from each group on the first,third,and seventh days after poisoning and dissected after anesthesia.The PQ content of the kidneys was measured using the sodium disulfite method.Hematoxylin-eosin staining of renal tissues was performed to detect pathological changes.Apelin expression in the renal tissues was detected using immunofluorescence.Western blotting was used to detect the expression levels of the following proteins in the kidney tissues:IL-6,TNF-α,apelin-APJ(the apelin-angiotensin receptor),NF-κB p65,caspase-1,caspase-8,glucose-regulated protein 78(GRP78),and the C/EBP homologous protein(CHOP).In in vitro study,a PQ toxicity model was established using human tubular epithelial cells treated with standard PQ.Twenty-four hours after poisoning,sivelestat and AH_(2)QDS were administered.The levels of oxidative stress in human renal tubular epithelial cells were assessed using a reactive oxygen species fluorescence probe.Results:The PQ content in the kidney tissues of the PQ group was higher than that of the PQ+AH_(2)QDS group.Hematoxylin-eosin staining showed extensive hemorrhage and congestion in the renal parenchyma of the PQ group.Vacuolar degeneration of the renal tubule epithelial cells,deposition of crescent-like red staining material in renal follicles,infiltration by a few inflammatory cells,and a small number of cast formation were also observed.However,these pathological changes were less severe in the PQ+sivelestat group and the PQ+AH_(2)QDS group(P<0.05).On the third day after poisoning,immunofluorescence assay showed that the level of apelin in the renal tissues was significantly higher in the PQ+AH_(2)QDS group than in the PQ group.Western blotting analysis results showed that IL-6,TNF-α,NF-κB p65,caspase-1,caspase-8,GRP78,and CHOP protein levels in the PQ group were higher than in the PQ+AH_(2)QDS group(P<0.05).The expression of apelin-APJ proteins in the PQ+AH_(2)QDS group was higher than in the PQ+sivelestat and PQ groups(P<0.05);this difference was significant on Day 3 and Day 7.The level of oxidative stress in the renal tubular epithelial cells of the PQ+AH_(2)QDS group and the PQ+sivelestat group was significantly lower than in the PQ group(P<0.05).Conclusions:This study confirms that AH_(2)QDS has a protective effect on PQ-poisoned kidneys and its positive effect is superior to that of sivelestat.The mechanism of the protective effects of AH_(2)QDS may be linked to reduction in cellular oxidative stress,PQ content of renal tissue,inflammatory injury,endoplasmic reticulum stress,and apoptosis.AH_(2)QDS may play a role in the treatment of PQ poisoning by upregulating the expression of the apelin-APJ.展开更多
Objective:To evaluate the effect of midkine on lipopolysaccharide(LPS)-induced airway smooth muscle cells(ASMCs).Methods:LPS-stimulated acute lung injury model was used to analyze the effect of midkine on ASMCs in vit...Objective:To evaluate the effect of midkine on lipopolysaccharide(LPS)-induced airway smooth muscle cells(ASMCs).Methods:LPS-stimulated acute lung injury model was used to analyze the effect of midkine on ASMCs in vitro.Recombinant midkine and midkine siRNA were used to investigate the role of Notch2 signaling pathway.Cell proliferation was assessed using Cell Counting Kit-8 assay.Additionally,apoptosis was measured by flow cytometry and protein and mRNA expression of midkine and Notch2 was assessed by Western blotting and qPCR,respectively.Immunofluorescence analysis was also conducted.Results:LPS increased the mRNA and protein expression of midkine and Notch2.Midkine silencing reduced LPS-induced midkine and Notch2 expression.In addition,midkine silencing further reduced the viability and increased apoptosis of ASMCs induced by LPS,which was attenuated by recombinant midkine.Conclusions:The midkine/Notch2 signaling pathway plays a regulatory role in ASMC proliferation and apoptosis in airway inflammation.展开更多
Nickel-based alloys have been considered as candidate structural materials used in generation IV nuclear reactors serving at high temperatures.In the present study,alloy 617 was irradiated with 180-keV helium ions to ...Nickel-based alloys have been considered as candidate structural materials used in generation IV nuclear reactors serving at high temperatures.In the present study,alloy 617 was irradiated with 180-keV helium ions to a fluence of 3.6×10^(17) ions/cm^(2) at room temperature.Throughout the cross-section transmission electron microscopy(TEM)image,numerous over-pressurized helium bubbles in spherical shape are observed with the actual concentration profile a little deeper than the SRIM predicted result.Post-implantation annealing was conducted at 700℃for 2 h to investigate the bubble evolution.The long-range migration of helium bubbles occurred during the annealing process,which makes the bubbles of the peak region transform into a faceted shape as well.Then the coarsening mechanism of helium bubbles at different depths is discussed and related to the migration and coalescence(MC)mechanism.With the diffusion of nickel atoms slowed down by the alloy elements,the migration and coalescence of bubbles are suppressed in alloy 617,leading to a better helium irradiation resistance.展开更多
Objective:To systematically evaluate the incidence of adverse reactions to coronavirus disease 2019(COVID-19)vaccination.Methods:We systematically searched PubMed,Embase,The Cochrane Library,Web of Science,CNKI,WanFan...Objective:To systematically evaluate the incidence of adverse reactions to coronavirus disease 2019(COVID-19)vaccination.Methods:We systematically searched PubMed,Embase,The Cochrane Library,Web of Science,CNKI,WanFang Data,and VIP Database from the inception of each database to August 31,2021.Randomized controlled clinical trials(RCTs)on the safety of different types of COVID-19 vaccines were retrieved and analyzed.A random or fixed-effects model was used with an odds ratio as the effect size.The quality of each reference was evaluated.The incidence of the adverse reactions of the placebo group and the vaccination group was compared.Heterogeneity and publication bias were taken care of by meta-regression and sub-group analyses.Results:A total of 13 articles were included,with 81287 subjects.Compared with the placebo group,the vaccination group showed a higher combined risk ratio(RR)of total adverse reactions(RR=1.67,95%CI:1.46-1.91,P<0.01),local adverse reactions(RR=2.86,95%CI:2.11-3.87,P<0.01),systemic adverse reactions(RR=1.25,95%CI:0.92-1.72,P=0.16),pain(RR=2.55,95%CI:1.75-3.70,P<0.01),swelling(RR=4.16,95%CI:1.71-10.17,P=0.002),fever(RR=2.34,95%CI:1.84-2.97,P<0.01),fatigue(RR=1.36,95%CI:1.32-1.41,P<0.01)and headache(RR=1.22,95%CI:1.18-1.26,P<0.01).The subgroup analysis showed the incidence of adverse reactions of the vaccination group after injection of the three COVID-19 vaccines(inactivated viral vaccines,mRNA vaccines and adenovirus vector vaccines)was higher than that of the placebo group,and the difference between the placebo group and the vaccination group in the mRNA vaccine subgroup and the adenovirus vector vaccine subgroup was statistically significant(P<0.01).The incidence of adverse reactions after injection of COVID-19 vaccine in subgroups of different ages was significantly higher than that in the placebo group(P<0.01).Conclusions:COVID-19 vaccines have a good safety,among which adenovirus vector vaccine has the highest incidence of adverse reactions.Both adolescents and adults vaccinated with novel coronavirus vaccine have a certain proportion of adverse reactions,but the symptoms are mild and can be relieved by themselves.Our meta-analysis can help boost global awareness of vaccine safety,promote mass vaccination,help build regional and global immune barriers and effectively curb the recurrency of COVID-19.展开更多
Paraquat is a bipyridine dichloride non-selective herbicide,which was widely used in the world in the last century.Now,paraquat is banned in most countries because of the extremely high lethality and the lack of speci...Paraquat is a bipyridine dichloride non-selective herbicide,which was widely used in the world in the last century.Now,paraquat is banned in most countries because of the extremely high lethality and the lack of specific detoxification drugs.However,death due to paraquat poisoning still occurs frequently,thus it is of great clinical significance to explore the molecular mechanism of paraquat poisoning and the detoxification drugs.Paraquat poisoning causes multiple dysfunction of the lung,liver,kidney,heart,and brain through complex molecular mechanisms.About the mechanism there are excessive inflammatory reaction theory,REDOX reaction imbalance theory,oxidative stress free radical damage theory,calcium overload theory,NO molecular damage and cell apoptosis theory,etc.For the treatment of paraquat poisoning,paraquat antibody,pathway target blocker and related factor antibody have been developed in recent years.Although certain effects have been achieved,the treatment efficiency has not been significantly improved.This paper summarized the mechanism of signal transduction pathways involved in lung injury induced by paraquat poisoning in order to provide a theoretical basis for further research.展开更多
Objective:Severe cases of coronavirus disease 2019(COVID-19)are expected to have a worse prognosis than mild cases.Shenhuang Granule(SHG)has been shown to be a safe and effective treatment for severe COVID-19 in a pre...Objective:Severe cases of coronavirus disease 2019(COVID-19)are expected to have a worse prognosis than mild cases.Shenhuang Granule(SHG)has been shown to be a safe and effective treatment for severe COVID-19 in a previous randomized clinical trial,but the active chemical constituents and underlying mechanisms of action remain unknown.The goal of this study is to explore the chemical basis and mechanisms of SHG in the treatment of severe COVID-19,using network pharmacology.Methods:Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was employed to screen chemical constituents of SHG.Putative therapeutic targets were predicted by searching traditional Chinese medicine system pharmacology database and analysis platform,Swiss Target Prediction,and Gene Expression Omnibus(GEO)databases.The target protein–protein interaction network and enrichment analysis were performed to investigate the hub genes and presumptive mechanisms.Molecular docking and molecular dynamics simulations were used to verify the stability and interaction between the key chemical constituents of SHG and COVID-19 protein targets.Results:Forty-five chemical constituents of SHG were identified along with 131 corresponding therapeutic targets,including hub genes such as HSP90AA1,MMP9,CXCL8,PTGS2,IFNG,DNMT1,TYMS,MDM2,HDAC3 and ABCB1.Functional enrichment analysis indicated that SHG mainly acted on the neuroactive ligand-receptor interaction,calcium signaling pathway and c AMP signaling pathway.Molecular docking showed that the key constituents had a good affinity with the severe acute respiratory syndrome coronavirus 2 protein targets.Molecular dynamics simulations indicated that ginsenoside Rg4 formed a stable protein-ligand complex with helicase.Conclusion:Multiple components of SHG regulated multiple targets to inhibit virus invasion and cytokine storm through several signaling pathways;this provides a scientific basis for clinical applications and further experiments.展开更多
基金supported by the National Natural Science Foundation of China (Nos.50571059 and 50615024)the Natural Science Foundation of Jiangsu Province,China (No.SBK200920379)the Program for New Century Excellent Talents in Chinese Universities (No.NCET-07-0536)
文摘Silver in the form of AgNO3 was added to ZnO-based varistor ceramics prepared by the solid-state reaction method.The effects of AgNO3 on both the microstructure and electrical properties of the varistors were studied in detail.The optimum addition amount of AgNO3 in ZnO-based varistors was also determined.The mechanism for grain growth inhibition by silver doping was also proposed.The results indicate that the varistor threshold voltage increases substantially along with the AgNO3 content increasing from 0 to 1.5mol%.Also,the introduction of AgNO3 can depress the mean grain size of ZnO,which is mainly responsible for the threshold voltage.Furthermore,the addition of AgNO3 results in a slight decrease of donor density and a more severe fall in the density of interface states,which cause a decline in barrier height and an increase in the depletion layer.
基金financially supported by the National Natural Science Foundation of China(No.51576103)the National S&T Major Project(No.ZX06901)
文摘NG-CT-10 and NG-CT-20 are newly developed grades of nuclear-grade graphite from China.In this study,their oxidation behaviors were experimentally investigated using thermal gravimetric analysis.Microstructural evolution before and after oxidation was investigated using scanning electron microscope,mercury intrusion,and Raman spectroscopy.The apparent activation energy of NG-CT-10 nuclear graphite is 161.4 kJ/mol in a reaction temperature range of 550–700℃and that of NG-CT-20 is 153.5 kJ/mol in a temperature range of 550–650℃.The activation energy in the inner diffusion control regime is approximately half that in the kinetics control regime.At high temperatures,the binder phase is preferentially oxidized over the filler particles and small pores are generated in the binder.No new large or deep pores are generated on the graphite surfaces.Oxygen can diffuse along the boundaries of filler particles and through the binder phase,but cannot diffuse into the spaces between the nanocrystallites in the filler particles.Filler particles are oxidized starting at their outer surfaces,and the sizes of nanocrystallites do not decrease following oxidation.
基金National Natural Science Foundation of China(No.81960351)Social Development Key Project of Hainan Province(No.ZDYF2019125)Hainan Provincial Natural Science Foundation of China(820QN398)Hainan Province Clinical Medical Center.
文摘Objective:To explore the protective effects of anthrahydroquinone-2,6-disulfonate(AH_(2)QDS)on the kidneys of paraquat(PQ)poisoned rats via the apelin-APJ pathway.Methods:Male Sprague Dawley rats were divided into four experimental groups:control,PQ,PQ+sivelestat,and PQ+AH_(2)QDS.The PQ+sivelestat group served as the positive control group.The model of poisoning was established via intragastric treatment with a 20%PQ pesticide solution at 200 mg/kg.Two hours after poisoning,the PQ+sivelestat group was treated with sivelestat,while the PQ+AH_(2)QDS group was given AH_(2)QDS.Six rats were selected from each group on the first,third,and seventh days after poisoning and dissected after anesthesia.The PQ content of the kidneys was measured using the sodium disulfite method.Hematoxylin-eosin staining of renal tissues was performed to detect pathological changes.Apelin expression in the renal tissues was detected using immunofluorescence.Western blotting was used to detect the expression levels of the following proteins in the kidney tissues:IL-6,TNF-α,apelin-APJ(the apelin-angiotensin receptor),NF-κB p65,caspase-1,caspase-8,glucose-regulated protein 78(GRP78),and the C/EBP homologous protein(CHOP).In in vitro study,a PQ toxicity model was established using human tubular epithelial cells treated with standard PQ.Twenty-four hours after poisoning,sivelestat and AH_(2)QDS were administered.The levels of oxidative stress in human renal tubular epithelial cells were assessed using a reactive oxygen species fluorescence probe.Results:The PQ content in the kidney tissues of the PQ group was higher than that of the PQ+AH_(2)QDS group.Hematoxylin-eosin staining showed extensive hemorrhage and congestion in the renal parenchyma of the PQ group.Vacuolar degeneration of the renal tubule epithelial cells,deposition of crescent-like red staining material in renal follicles,infiltration by a few inflammatory cells,and a small number of cast formation were also observed.However,these pathological changes were less severe in the PQ+sivelestat group and the PQ+AH_(2)QDS group(P<0.05).On the third day after poisoning,immunofluorescence assay showed that the level of apelin in the renal tissues was significantly higher in the PQ+AH_(2)QDS group than in the PQ group.Western blotting analysis results showed that IL-6,TNF-α,NF-κB p65,caspase-1,caspase-8,GRP78,and CHOP protein levels in the PQ group were higher than in the PQ+AH_(2)QDS group(P<0.05).The expression of apelin-APJ proteins in the PQ+AH_(2)QDS group was higher than in the PQ+sivelestat and PQ groups(P<0.05);this difference was significant on Day 3 and Day 7.The level of oxidative stress in the renal tubular epithelial cells of the PQ+AH_(2)QDS group and the PQ+sivelestat group was significantly lower than in the PQ group(P<0.05).Conclusions:This study confirms that AH_(2)QDS has a protective effect on PQ-poisoned kidneys and its positive effect is superior to that of sivelestat.The mechanism of the protective effects of AH_(2)QDS may be linked to reduction in cellular oxidative stress,PQ content of renal tissue,inflammatory injury,endoplasmic reticulum stress,and apoptosis.AH_(2)QDS may play a role in the treatment of PQ poisoning by upregulating the expression of the apelin-APJ.
基金supported by the National Natural Science Foundation of China(NO.81660011,81960351)Hainan Provincial Social Development Foundation(NO.ZDYFXGFY2020004)Hainan Provincial Medical and Health Research Project(NO.22A200036).
文摘Objective:To evaluate the effect of midkine on lipopolysaccharide(LPS)-induced airway smooth muscle cells(ASMCs).Methods:LPS-stimulated acute lung injury model was used to analyze the effect of midkine on ASMCs in vitro.Recombinant midkine and midkine siRNA were used to investigate the role of Notch2 signaling pathway.Cell proliferation was assessed using Cell Counting Kit-8 assay.Additionally,apoptosis was measured by flow cytometry and protein and mRNA expression of midkine and Notch2 was assessed by Western blotting and qPCR,respectively.Immunofluorescence analysis was also conducted.Results:LPS increased the mRNA and protein expression of midkine and Notch2.Midkine silencing reduced LPS-induced midkine and Notch2 expression.In addition,midkine silencing further reduced the viability and increased apoptosis of ASMCs induced by LPS,which was attenuated by recombinant midkine.Conclusions:The midkine/Notch2 signaling pathway plays a regulatory role in ASMC proliferation and apoptosis in airway inflammation.
基金Project supported by the Special Funds for the Key Research and Development Program of the Ministry of Science and Technology of China(Grant Nos.2017YFB0702201 and 2020YFB1901800)the National Natural Science Foundation of China(Grant Nos.11975135 and 12005017).
文摘Nickel-based alloys have been considered as candidate structural materials used in generation IV nuclear reactors serving at high temperatures.In the present study,alloy 617 was irradiated with 180-keV helium ions to a fluence of 3.6×10^(17) ions/cm^(2) at room temperature.Throughout the cross-section transmission electron microscopy(TEM)image,numerous over-pressurized helium bubbles in spherical shape are observed with the actual concentration profile a little deeper than the SRIM predicted result.Post-implantation annealing was conducted at 700℃for 2 h to investigate the bubble evolution.The long-range migration of helium bubbles occurred during the annealing process,which makes the bubbles of the peak region transform into a faceted shape as well.Then the coarsening mechanism of helium bubbles at different depths is discussed and related to the migration and coalescence(MC)mechanism.With the diffusion of nickel atoms slowed down by the alloy elements,the migration and coalescence of bubbles are suppressed in alloy 617,leading to a better helium irradiation resistance.
基金funded the Province Natural Science key Foundation of Hainan(No:ZDYFXGFY2020004 and No:ZDYF 2019125)the National Natural Science Foundation of China(No:81960351)Hainan Province Clinical Medical Center.
文摘Objective:To systematically evaluate the incidence of adverse reactions to coronavirus disease 2019(COVID-19)vaccination.Methods:We systematically searched PubMed,Embase,The Cochrane Library,Web of Science,CNKI,WanFang Data,and VIP Database from the inception of each database to August 31,2021.Randomized controlled clinical trials(RCTs)on the safety of different types of COVID-19 vaccines were retrieved and analyzed.A random or fixed-effects model was used with an odds ratio as the effect size.The quality of each reference was evaluated.The incidence of the adverse reactions of the placebo group and the vaccination group was compared.Heterogeneity and publication bias were taken care of by meta-regression and sub-group analyses.Results:A total of 13 articles were included,with 81287 subjects.Compared with the placebo group,the vaccination group showed a higher combined risk ratio(RR)of total adverse reactions(RR=1.67,95%CI:1.46-1.91,P<0.01),local adverse reactions(RR=2.86,95%CI:2.11-3.87,P<0.01),systemic adverse reactions(RR=1.25,95%CI:0.92-1.72,P=0.16),pain(RR=2.55,95%CI:1.75-3.70,P<0.01),swelling(RR=4.16,95%CI:1.71-10.17,P=0.002),fever(RR=2.34,95%CI:1.84-2.97,P<0.01),fatigue(RR=1.36,95%CI:1.32-1.41,P<0.01)and headache(RR=1.22,95%CI:1.18-1.26,P<0.01).The subgroup analysis showed the incidence of adverse reactions of the vaccination group after injection of the three COVID-19 vaccines(inactivated viral vaccines,mRNA vaccines and adenovirus vector vaccines)was higher than that of the placebo group,and the difference between the placebo group and the vaccination group in the mRNA vaccine subgroup and the adenovirus vector vaccine subgroup was statistically significant(P<0.01).The incidence of adverse reactions after injection of COVID-19 vaccine in subgroups of different ages was significantly higher than that in the placebo group(P<0.01).Conclusions:COVID-19 vaccines have a good safety,among which adenovirus vector vaccine has the highest incidence of adverse reactions.Both adolescents and adults vaccinated with novel coronavirus vaccine have a certain proportion of adverse reactions,but the symptoms are mild and can be relieved by themselves.Our meta-analysis can help boost global awareness of vaccine safety,promote mass vaccination,help build regional and global immune barriers and effectively curb the recurrency of COVID-19.
基金Natural Science Foundation of China-Regional Project(No.81960351)Social development key project of Hainan province(No.ZDYF2019125).
文摘Paraquat is a bipyridine dichloride non-selective herbicide,which was widely used in the world in the last century.Now,paraquat is banned in most countries because of the extremely high lethality and the lack of specific detoxification drugs.However,death due to paraquat poisoning still occurs frequently,thus it is of great clinical significance to explore the molecular mechanism of paraquat poisoning and the detoxification drugs.Paraquat poisoning causes multiple dysfunction of the lung,liver,kidney,heart,and brain through complex molecular mechanisms.About the mechanism there are excessive inflammatory reaction theory,REDOX reaction imbalance theory,oxidative stress free radical damage theory,calcium overload theory,NO molecular damage and cell apoptosis theory,etc.For the treatment of paraquat poisoning,paraquat antibody,pathway target blocker and related factor antibody have been developed in recent years.Although certain effects have been achieved,the treatment efficiency has not been significantly improved.This paper summarized the mechanism of signal transduction pathways involved in lung injury induced by paraquat poisoning in order to provide a theoretical basis for further research.
基金supported by the National Key Research and Development Program(No.2018YFC1705900)the Emergency Committee of the World Federation of Chinese Medicine Societies and Shanghai Society of Traditional Chinese Medicine Novel Coronavirus Pneumonia Emergency Tackling Key Project(No.SJZLJZ.N01)。
文摘Objective:Severe cases of coronavirus disease 2019(COVID-19)are expected to have a worse prognosis than mild cases.Shenhuang Granule(SHG)has been shown to be a safe and effective treatment for severe COVID-19 in a previous randomized clinical trial,but the active chemical constituents and underlying mechanisms of action remain unknown.The goal of this study is to explore the chemical basis and mechanisms of SHG in the treatment of severe COVID-19,using network pharmacology.Methods:Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry was employed to screen chemical constituents of SHG.Putative therapeutic targets were predicted by searching traditional Chinese medicine system pharmacology database and analysis platform,Swiss Target Prediction,and Gene Expression Omnibus(GEO)databases.The target protein–protein interaction network and enrichment analysis were performed to investigate the hub genes and presumptive mechanisms.Molecular docking and molecular dynamics simulations were used to verify the stability and interaction between the key chemical constituents of SHG and COVID-19 protein targets.Results:Forty-five chemical constituents of SHG were identified along with 131 corresponding therapeutic targets,including hub genes such as HSP90AA1,MMP9,CXCL8,PTGS2,IFNG,DNMT1,TYMS,MDM2,HDAC3 and ABCB1.Functional enrichment analysis indicated that SHG mainly acted on the neuroactive ligand-receptor interaction,calcium signaling pathway and c AMP signaling pathway.Molecular docking showed that the key constituents had a good affinity with the severe acute respiratory syndrome coronavirus 2 protein targets.Molecular dynamics simulations indicated that ginsenoside Rg4 formed a stable protein-ligand complex with helicase.Conclusion:Multiple components of SHG regulated multiple targets to inhibit virus invasion and cytokine storm through several signaling pathways;this provides a scientific basis for clinical applications and further experiments.
