目的:利用R语言数据挖掘技术分析脓毒症的中医证型及用药规律,为脓毒症临床中医诊疗方案提供参考。方法:通过检索PubMed、Web of Science、中国知网、万方、维普和中国生物医学文献数据库,收集从建库至2023年12月31日收录的符合纳入标...目的:利用R语言数据挖掘技术分析脓毒症的中医证型及用药规律,为脓毒症临床中医诊疗方案提供参考。方法:通过检索PubMed、Web of Science、中国知网、万方、维普和中国生物医学文献数据库,收集从建库至2023年12月31日收录的符合纳入标准的中医药治疗脓毒症临床研究文献,建立相关处方数据库。运用Excel整理并分析方药信息,包括中医辨证分型、治法治则,中药的使用频次、性味、归经、功效等;并利用R语言进行关联规则分析及聚类分析。结果:共检索出文献10345篇,纳入分析280篇,涉及中药215味,其中排名前10的中药分别是大黄、甘草、赤芍、厚朴、黄芪、芒硝、黄芩、丹参、地黄、枳实;四气以寒、温为主,五味以苦、甘、辛为主,归经以脾、胃、肺为主,功效以清热、补虚、泻下为主,证型以热毒内盛证、瘀毒内阻证为主。关联规则分析得到核心组方为大黄、芒硝、枳实、厚朴、当归、川芎、赤芍、桃仁、地黄、红花。高频药物聚类分析得到4个聚类群,适用于不同证型。结论:治疗脓毒症的用药规律以清热、泻下、化瘀、补虚为主,核心证型-处方有4类,临床上应根据患者的证候特点进行辨证论治,在核心证型-处方的基础上随证加减。展开更多
An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease prog...An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.展开更多
Pear(Pyrus bretschneideri)fruit stone cells are primarily composed of lignin and have strongly lignified cell walls.The presence of stone cells has a negative influence on fruit texture and taste,and thus the reductio...Pear(Pyrus bretschneideri)fruit stone cells are primarily composed of lignin and have strongly lignified cell walls.The presence of stone cells has a negative influence on fruit texture and taste,and thus the reduction of stone cell content in pear fruit is a key goal of breeding efforts.However,research into the key transcription factors and regulatory networks associated with pear fruit stone cell formation have been limited.We here used a combination of co-expression network and expression quantitative trait locus(eQTL)analyses in 206 pear cultivars with different stone cell contents to identify relevant genes;these analyses uncovered the gene PbrMYB4,a R2R3 MYB transcription factor gene.There was a strong positive correlation between relative PbrMYB4 expression levels in the fruit flesh and stone cell/lignin contents.Overexpression of PbrMYB4 significantly increased the lignin contents,whereas silencing of PbrMYB4 had the opposite effect,decreasing the contents of lignin.PbrMYB4 overexpression in pear calli significantly promoted lignin biosynthesis.In Arabidopsis thaliana,PbrMYB4 overexpression resulted in increasing lignin deposition,cell wall thickness of vessels and xylary fiber,and accelerating expression level of lignin biosynthetic genes.PbrMYB4 was found to activate 4-Coumarate:Coenzyme A Ligase(Pbr4CL1)by binding to AC-I elements in the promoter regions,as demonstrated with dual-luciferase reporter assays and a yeast one-hybrid assay.These results demonstrated that PbrMYB4 positively regulated lignin biosynthesis in pear fruit stone cells by activating lignin biosynthesis genes.This study improves our understanding of the gene regulatory networks associated with stone cell formation in pear fruit,providing guidance for molecular breeding of pear varieties with low stone cell content.展开更多
文摘目的:利用R语言数据挖掘技术分析脓毒症的中医证型及用药规律,为脓毒症临床中医诊疗方案提供参考。方法:通过检索PubMed、Web of Science、中国知网、万方、维普和中国生物医学文献数据库,收集从建库至2023年12月31日收录的符合纳入标准的中医药治疗脓毒症临床研究文献,建立相关处方数据库。运用Excel整理并分析方药信息,包括中医辨证分型、治法治则,中药的使用频次、性味、归经、功效等;并利用R语言进行关联规则分析及聚类分析。结果:共检索出文献10345篇,纳入分析280篇,涉及中药215味,其中排名前10的中药分别是大黄、甘草、赤芍、厚朴、黄芪、芒硝、黄芩、丹参、地黄、枳实;四气以寒、温为主,五味以苦、甘、辛为主,归经以脾、胃、肺为主,功效以清热、补虚、泻下为主,证型以热毒内盛证、瘀毒内阻证为主。关联规则分析得到核心组方为大黄、芒硝、枳实、厚朴、当归、川芎、赤芍、桃仁、地黄、红花。高频药物聚类分析得到4个聚类群,适用于不同证型。结论:治疗脓毒症的用药规律以清热、泻下、化瘀、补虚为主,核心证型-处方有4类,临床上应根据患者的证候特点进行辨证论治,在核心证型-处方的基础上随证加减。
基金supported by a grant from Ministry of Science,Technological Development and Innovation,Serbia,No.451-03-68/2022-14/200178(to NN)University of Defence,No.MFVMA/02/22-24(to MN)。
文摘An imbalance in adenosine-mediated signaling,particularly the increased A_(2A)R-mediated signaling,plays a role in the pathogenesis of Parkinson's disease.Existing therapeutic approaches fail to alter disease progression,demonstrating the need for novel approaches in PD.Repetitive transcranial magnetic stimulation is a non-invasive approach that has been shown to improve motor and non-motor symptoms of Parkinson's disease.However,the underlying mechanisms of the beneficial effects of repetitive transcranial magnetic stimulation remain unknown.The purpose of this study is to investigate the extent to which the beneficial effects of prolonged intermittent theta burst stimulation in the 6-hydroxydopamine model of experimental parkinsonism are based on modulation of adenosine-mediated signaling.Animals with unilateral 6-hydroxydopamine lesions underwent intermittent theta burst stimulation for 3 weeks and were tested for motor skills using the Rotarod test.Immunoblot,quantitative reverse transcription polymerase chain reaction,immunohistochemistry,and biochemical analysis of components of adenosine-mediated signaling were performed on the synaptosomal fraction of the lesioned caudate putamen.Prolonged intermittent theta burst stimulation improved motor symptoms in 6-hydroxydopamine-lesioned animals.A 6-hydroxydopamine lesion resulted in progressive loss of dopaminergic neurons in the caudate putamen.Treatment with intermittent theta burst stimulation began 7 days after the lesion,coinciding with the onset of motor symptoms.After treatment with prolonged intermittent theta burst stimulation,complete motor recovery was observed.This improvement was accompanied by downregulation of the e N/CD73-A_(2A)R pathway and a return to physiological levels of A_(1)R-adenosine deaminase 1 after 3 weeks of intermittent theta burst stimulation.Our results demonstrated that 6-hydroxydopamine-induced degeneration reduced the expression of A_(1)R and elevated the expression of A_(2A)R.Intermittent theta burst stimulation reversed these effects by restoring the abundances of A_(1)R and A_(2A)R to control levels.The shift in ARs expression likely restored the balance between dopamine-adenosine signaling,ultimately leading to the recovery of motor control.
基金funded by the Science Foundation of China(Grant No.32230097)Earmarked Fund for China Agriculture Research System(Grant No.CARS-28)+2 种基金the Earmarked Fund for Jiangsu Agricultural Industry Technology System(Grant No.JATS[2023]412)Natural Science Foundation of Jiangsu Province for Young Scholar(Grant No.BK20221010)supported by the high-performance computing platform of Bioinformatics Center,Nanjing Agricultural University。
文摘Pear(Pyrus bretschneideri)fruit stone cells are primarily composed of lignin and have strongly lignified cell walls.The presence of stone cells has a negative influence on fruit texture and taste,and thus the reduction of stone cell content in pear fruit is a key goal of breeding efforts.However,research into the key transcription factors and regulatory networks associated with pear fruit stone cell formation have been limited.We here used a combination of co-expression network and expression quantitative trait locus(eQTL)analyses in 206 pear cultivars with different stone cell contents to identify relevant genes;these analyses uncovered the gene PbrMYB4,a R2R3 MYB transcription factor gene.There was a strong positive correlation between relative PbrMYB4 expression levels in the fruit flesh and stone cell/lignin contents.Overexpression of PbrMYB4 significantly increased the lignin contents,whereas silencing of PbrMYB4 had the opposite effect,decreasing the contents of lignin.PbrMYB4 overexpression in pear calli significantly promoted lignin biosynthesis.In Arabidopsis thaliana,PbrMYB4 overexpression resulted in increasing lignin deposition,cell wall thickness of vessels and xylary fiber,and accelerating expression level of lignin biosynthetic genes.PbrMYB4 was found to activate 4-Coumarate:Coenzyme A Ligase(Pbr4CL1)by binding to AC-I elements in the promoter regions,as demonstrated with dual-luciferase reporter assays and a yeast one-hybrid assay.These results demonstrated that PbrMYB4 positively regulated lignin biosynthesis in pear fruit stone cells by activating lignin biosynthesis genes.This study improves our understanding of the gene regulatory networks associated with stone cell formation in pear fruit,providing guidance for molecular breeding of pear varieties with low stone cell content.