基于VOSviewer和CiteSpace的国内外“肺肠同治”研究可视化分析

目的分析国内外“肺肠同治”相关研究现状及发展趋势,为中医理论的传承与创新提供参考。方法以中国知网(CNKI)、Web of Science(WOS)核心数据库为数据来源,搜集2000年以来“肺肠同治”相关理论探讨和实际应用文献,采用VOSviewer和CiteSpace软件对发文时间、期刊、地域分布、关键词等进行可视化分析。结果共纳入中文文献751篇、英文文献384篇,发文量整体呈上升趋势,2015年后进入快速发展期。发文量排名第一的中文和英文期刊分别为《中华中医药杂志》(38篇)、Frontiers in Immunology(25篇)。北京中医药大学是中文文献发文量最高的机构(90篇),并与16家机构存在紧密的合作关系;英文文献发文量最高的机构为Institut National de la Sante et de la Recherche Medicale(12篇)和University of California System(12篇)。基于VOSviewer中文关键词形成12个聚类、英文关键词形成7个聚类,研究热点主要集中在经典理论挖掘、肺肠相关疾病、方药、机制探索、相关因子等方面。结论“肺肠同治”研究呈上升发展趋势,预测未来研究热点及前沿仍在肠-肺轴、肺肠微生物等方面。不同机构间应加强和深化合作、促进学术交流,注重运用现代科技手段研究中医理论,促进中医药理论的国际传播。

Exploring the pharmacological mechanism of Wuzhuyu decoction on hepatocellular carcinoma using network pharmacology

BACKGROUND Wuzhuyu decoction,a traditional Chinese medicinal formula,is effective in treating hepatocellular carcinoma(HCC).AIM To explore the potential mechanism of action of Wuzhuyu decoction against HCC.METHODS The active components of each Chinese herbal medicinal ingredient in Wuzhuyu decoction and their targets were obtained from the Traditional Chinese Medicine Database and Analysis Platform.HCC was used as a search query in GeneCards,Online Mendelian Inheritance in Man,Malacards,DisGeNET,Therapeutic Target Database,and Comparative Toxicogenomics Database.The overlapping targets of the Wuzhuyu decoction and HCC were defined,and then protein-protein interaction,Gene Ontology,and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed.CytoHubba was used to select hub genes,and their binding activities and key active components were verified using molecular docking.RESULTS A total of 764 compounds,77 active compounds,and 204 potential target genes were identified in Wuzhuyu decoction.For HCC,9468 potential therapeutic target genes were identified by combining the results from the six databases and removing duplicates.A total of 179 overlapping targets of Wuzhuyu decoction and HCC were defined,including 10 hub genes(tumor necrosis factor,interleukin-6,AKT1,TP53,caspase-3,mitogen-activated protein kinase 1,epidermal growth factor receptor,MYC,mitogen-activated protein kinase 8,and JUN).There were six main active components(quercetin,kaempferol,ginsenoside Rh2,rutaecarpine,β-carotene,andβ-sitosterol)that may act on hub genes to treat HCC in Wuzhuyu decoction.Kyoto Encyclopedia of Genes and Genomes enrichment analysis mainly involved the mitogen-activated protein kinase,p53,phosphatidylinositol-4,5-bisphosphate 3-kinase-Akt,Janus kinase-signal transducer of activators of transcription,and Hippo signaling pathways.Further verification based on molecular docking results showed that the small molecule compounds(quercetin,kaempferol,ginsenoside Rh2,rutaecarpine,β-carotene,andβ-sitosterol)contained in Wuzhuyu decoction generally have excellent binding affinity to the macromolecular target proteins encoded by the top 10 genes.

Comparison and Evaluation of Several Dermatophagoides Pteronyssinus Allergen Extracts for Skin Prick Test

Objective To evaluate the significance of several Dermatophagoides pteronyssinus allergen extracts for skin prick test(SPT) in patients allergic to Dermatophagoides pteronyssinus.Methods Two hundred and nineteen patients enrolled in Peking Union Medical College Hospital underwent SPT and serum specific IgE assay to detect the Dermatophagoides pteronyssinus allergen.Three kinds of house dust mite allergen extracts were used for SPT,including the Dermatophagoides pteronyssinus extract prepared by our laboratory(group A),standardized Dermatophagoides pteronyssinus extract(group B),and mixed extracts of Dermatophagoides pteronyssinus and Dermatophagoides farinae(group C).Human serum specific IgE result was regarded as the reference standard for diagnosis of Dermatophagoides pteronyssinus allergy.The receiver operating characteristic(ROC) curve was used to evaluate the diagnostic performance of SPT with the extracts of three groups.Results SPT results showed that the median wheal diameter of group A,group B,and group C was 0.43,0.35,and 0.28 cm,respectively,with significant difference among three groups(P<0.05).The difference was significant between group A and B(P<0.01) as well as group A and C(P<0.01),but not between group B and C(P>0.05).There was no local urticaria or systemic allergic reactions following the procedure of SPT.Local reaction was observed in 5 patients and delayed reaction was in 2 patients of group A.As for group B and C,local reaction occurred in 3 cases and delayed reaction in 2 cases in each group.The area under ROC curve of SPT with extract in group A,group B,and group C was 0.765,0.801,and 0.782,respectively.Based on the detection results of serum specific IgE,the sensitivity of SPT in diagnosis of Dermato-phagoides pteronyssinus allergy with extract of group A,group B,and group C was 92.4%,87.0%,and 81.5%,and the specificity was 60.6%,73.2%,and 74.8%,respectively.Conclusion The Dermatophagoides pteronyssinus extract for SPT prepared by our laboratory offers good sensitivity and specificity comparable to commercially available allergen extracts,and it may be an appropriate candidate for clinical screening and diagnosis of Dermatophagoides pteronyssinus allergy.

A New Topology Pattern for AC-DC Mixed Microgrid

In order to realize the modular design of the microgrid, this paper proposed a new modular topology for the AC-DC mixed microgrid. In that topology, the AC microgrid unit and the DC microgrid unit were packaged together by the back-to-back converter. The battery-supercapacitor hybrid energy storage system was connected to the DC bus of back-to-back converter. By the reasonable design on the battery-supercapacitor hybrid system, the energy storage system could supply the rapid power and energy support for the microgrid spontaneously. The mathematical model and the control algorithm of that microgrid topology were studied. By the simulation analysis, it can be concluded that AC-DC mixed modular microgrid topology could operate steadily on both the grid-connected mode and the isolated mode. Furthermore, we can conclude by the simulation that the designed modular microgrid could operate uninterrupted when the microgrid topology switched from the grid-connected mode to the isolated mode. The seamless switching became the natural property for the modular microgrid. As a result, the modular microgrid topology can be considered as a usual power/load module to realize the friendly power interaction with the power grid.

Design and characterization of a bifunctional bybrid antibacterial peptide LLH for bactericidal/endotoxin neutralization effects

Objective:To design a bi-functional antimicrobial peptide with bactericidal and endotoxin neutralization activity,and explore its bactericidal properties.Methods:The LBP(86-99)peptides and HLF(1-11)peptides were connected by a GGGS flexible 4-peptide linker to obtain the bi-functional antimicrobial peptide,which was named LLH.The secondary structure characteristics of LLH were analyzed by Emboss software.The minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of LLH against Escherichia coli ATCC25922 and DH5αwere determined by the microtiter broth dilution method.The bactericidal kinetics of LLH was characterized and its effect on endotoxin neutralization was determined.The hemolysis of LLH was evaluated.Results:LLH carried a positive charge of+9,exhibitedβ-folding andβ-corner structure,and had strong hydrophobicity.The MIC of LLH against Escherichia coli ATCC25922 and DH5αwas 4μM,and the MBC of LLH against Escherichia coli ATCC25922 and DH5αwas 8 and 4μM,respectively.LLH showed rapid bactericidal effects and significantly neutralized the endotoxin released in the sterilization process as well as reducing release of endotoxin.LLH showed no significant hemolysis at concentrations up to 400μg/mL.Conclusion:LLH produces dual effects of rapid sterilization and endotoxin neutralization,and does not induce significant hemolysis.

Chlorogenic acid modulates glucose and lipid metabolisms via AMPK activation in HepG2 cells and shows its anti-hyperglycemic effect on streptozocin-induced diabetic mice

Objective:In this study,we focus on the hypoglycemic effects of chlorogenic acid(CGA)in vitro and in vivo and its mechanism base on regulate glucose and lipid metabolism via AMPK activation.Methods:The cytotoxicity,glucose consumption and intracellular triglyceride assay were been detected by commercial kits.The western blots were used to detection the associated protein levels after CGA treatment,and the inhibiter blocking experiments were also be done.In vivo experiment,the fasting blood-glucose,lipid metabolism,liver function,insulin resistance,glucose tolerance,and pathological change were assessed on streptozocin induced diabetic mice.Results:We found that CGA exhibited no cytotoxicity at concentrations of 100μM,it caused a significant increasing of glucose consumption and reducing of the PA-BSA induced intracellular TG level on HepG2 cells at 50μM and 100μM treatment,CGA exhibited up-regulating the level of p-AMPK(Thr172)and p-ACC(Ser79)in dose-dependent manners in vitro and in vivo.The stimulating activities of CGA on AMPK were completely blocked by compound c(CC)on HepG2 cells.And the efficacies of CGA on glucose consumption and intracellular TG accumulation were also completely blocked by CC pretreatment.The CGA also exhibited potent anti-diabetic effects with hypoglycemic activity,improve insulin resistance and glucose tolerance,regulate glucose and lipid metabolism and protect the liver function in vivo.Conclusion:Our results suggested that CGA can regulate glucose and lipid metabolism by AMPK activation,and exhibit potent anti-hyperglycemic effect in streptozocin induced diabetes mice,and may be used as a potential effective anti-diabetes drug.

不同针灸疗法治疗中风后痉挛性偏瘫的网状Meta分析

Objective:To perform a network meta-analysis on four commonly used acupuncture therapies(electroacupuncture,fire acupuncture,warm acupuncture,and filiform needling) and rehabilitation therapy in the treatment of post-stroke spastic hemiplegia so as to compare the differences in clinical therapeutic effect between acupuncture therapy and rehabilitation therapy as well as among different therapeutic methods of acupuncture.Methods:A computer-based retrieval was conducted in Chinese and English databases,i.e.CNKI,WanFang,VIP,SinoMed,PubMed,Embase,Web of Science and Cochrane library.The search period limit was from the database establishment to April 17,2020.Data analysis was performed through Revman 5.3,Gemtc 0.14.3 and Stata 14.2.Results:A total of 27 trials were finally eligible,including 1880 patients,943 patients of which were in observation group and 937 patients in control group.In terms of the improvement of effective rate,electroacupuncture,fire needling,warm acupuncture and filiform needling methods were all better than rehabilitation therapy,and among which,warm acupuncture was the highest in probability to be the optimal measure.Regarding the improvement in Fugl-Meyer Assessment(FMA) motor function score,fire needling,warm acupuncture and filiform needling methods were all better than rehabilitation therapy,and among which,fire needling method was the highest in probability to be the optimal measure.In view of the improvement of BI score,fire needling method was better than electroacupuncture and filiform needling method,while,warm acupuncture was better than electroacupuncture,thus,fire needling method may be the optimal measure.For the modified Ashworth muscular tension assessment,there was no significant differences in pairwise comparison among different interventions and warm acupuncture was probably the optimal measure.Conclusion:The overall therapeutic effect of 4 acupuncture therapies is better than rehabilitation therapy on post-stroke spastic hemiplegia,respectively,among which,the therapeutic effect of warm acupuncture and fire needling method is the best.However,because of a limitation of the varieties of acupuncturemoxibustion therapy and the number of included trials,it needs to conduct more rigorous and scientific randomized controlled trials so that this conclusion can be further confirmed.

Astrocyte-Derived Lactate Modulates the Passive Coping Response to Behavioral Challenge in Male Mice

Every organism inevitably experiences stress. In the face of acute, intense stress, for example, periods of passivity occur when an organism's actions fail to overcome the challenge. The occurrence of inactive behavior may indicate that struggling would most likely be fruitless.Repeated serious stress has been associated with mood disorders such as depression. The modulation of passive coping response patterns has been explored with a focus on the circuit level. However, the cellular and molecular mechanisms are largely uncharacterized. Here, we report that lactate is a key factor in the astrocytic modulation of the passive coping response to behavioral challenge in adult mice. We found increased extracellular lactate in the medial prefrontal cortex(mPFC) when mice experienced the forced swimming test(FST). Furthermore, we discovered that disturbing astrocytic glycogenolysis, which is a key step for lactate production in the mPFC, decreased the duration of immobility in the FST. Knocking down monocarboxylate transporter 4(MCT4), which is expressed exclusively in astrocytes and transports lactate from astrocytes to the extracellular space, caused similar results in the FST. The behavioral effect of both the pharmacological disturbance of astrocytic glycogenolysis and viral disruption of MCT4 expression was rescued via the administration of L-lactate. Moreover, we found that both pharmacological and viral modulation of astrocytederived lactate in mPFC slices increased the excitability of layer V pyramidal neurons, and this enhancement was reversed by exogenous L-lactate administration. These results highlight astrocyte-derived lactate as a biological mechanism underlying the passive coping response to behavioral challenge and may provide new strategies to prevent mood disorders.