The co-occurrence of plasmid-mediated multidrug resistance and hypervirulence in epidemic carbapenem-resistant Klebsiella pneumoniae has emerged as a global public health issue.In this study,an ST23 carbapenem-resista...The co-occurrence of plasmid-mediated multidrug resistance and hypervirulence in epidemic carbapenem-resistant Klebsiella pneumoniae has emerged as a global public health issue.In this study,an ST23 carbapenem-resistant hyper-virulent K.pneumoniae(CR-HvKP)strain VH1-2 was identified from cucumber in China and harbored a novel hybrid plasmid pVH1-2-VIR.The plasmid pVH1-2-VIR carrying both virulence and multidrug-resistance(MDR)genes was likely generated through the recombination of a virulence plasmid and an IncFIIK conjugative MDR plasmid in clinical ST2318622 isolated from a sputum sample.The plasmid pVH1-2-VIR exhibited the capacity for transfer to the clinical ST11 carbapenem-resistant K.pneumoniae(CRKP)strain via conjugation assay.Acquisition of pVH1-2-VIR plasmid directly converted a CRKP into CR-HvKP strain characterized by hypermucoviscosity,heightened virulence for Galleria mellonella larvae,and increased colonization ability in the mouse intestine.The emergence of such a hybrid plasmid may expedite the spread of CR-HvKP strains,posing a significant risk to human health.展开更多
Objective:To observe the effect of moxibustion on the expression of N-methyl-D-aspartic acid(NMDA)receptor subtype 2B(NR2B)in the hippocampus of rheumatoid arthritis(RA)rats,and to explore the analgesic mechanisms of ...Objective:To observe the effect of moxibustion on the expression of N-methyl-D-aspartic acid(NMDA)receptor subtype 2B(NR2B)in the hippocampus of rheumatoid arthritis(RA)rats,and to explore the analgesic mechanisms of moxibustion in RA treatment.Methods:Sixty male Sprague-Dawley rats were randomly divided into a normal group,a model group,a moxibustion group,a moxibustion+NMDA receptor antagonist(AP-5)group,and a moxibustion+NMDA receptor agonist(NMDA)group,with 12 rats in each group.Except for the normal group,rats in the other four groups were treated with complete Freund's adjuvant in a windy,cold,and damp environment to replicate RA models.Rats in the moxibustion group received suspended moxibustion with moxa sticks at Shenshu(BL23)and Zusanli(ST36),and the two points were used alternately.After intraperitoneal injection of AP-5 or NMDA,rats in the moxibustion+AP-5 group and the moxibustion+NMDA group received the same moxibustion intervention as in the moxibustion group,once a day for 15 d.The thermal withdrawal latency(TWL)of rats in each group was detected before and after modeling and after the 15-day intervention.After the 15-day intervention,hematoxylin-eosin staining was performed to observe the pathological changes in knee joints.The real-time fluorescence quantitative polymerase chain reaction method was used to detect the mRNA expression of NR2B in the hippocampus;Western blotting assay was used to detect the protein and the phosphorylated protein expression of hippocampal NR2B.Results:The synovial tissue was proliferated,the synovial lining was significantly thickened,the pannus was formed,and the cartilage and bone tissues were significantly damaged in the model group.After intervention,the pathological morphology of the knee joints in the moxibustion group,the moxibustion+AP-5 group,and the moxibustion+NMDA group was significantly improved,and the improvement in the moxibustion+AP-5 group was more notable than that in the moxibustion+NMDA group.Compared with the normal group,the TWL was significantly decreased(P<0.01),and the mRNA,protein,and phosphorylated protein expression levels of hippocampal NR2B were significantly increased in the model group(P<0.01).Compared with the model group,the TWL of each intervention group was significantly increased(P<0.01 or P<0.05),and the mRNA,protein,and phosphorylated protein expression levels of hippocampal NR2B were significantly decreased(P<0.01).Compared with the moxibustion group,the TWL was significantly increased(P<0.01),and the mRNA,protein,and phosphorylated protein expression levels of hippocampal NR2B were significantly decreased in the moxibustion+AP-5 group(P<0.01);the TWL was significantly decreased(P<0.01),and the mRNA,protein,and phosphorylated protein expression levels of hippocampal NR2B were significantly increased in the moxibustion+NMDA group(P<0.01).Conclusion:Moxibustion reduces hyperalgesia in RA inflammatory rats.The analgesic effect may be related to the decrease in the expression and phosphorylation levels of NR2B in the hippocampus.展开更多
基金supported in part by the Foundation for Innovative Research Groups of the National Natural Science Foundation of China(32121004)Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program(2019BT02N054)+4 种基金Laboratory of Lingnan Modern Agriculture Project(NT2021006)Guangdong Major Project of Basic and Applied Basic Research(grant 2020B0301030007)Innovation Team Project of Guangdong University(2019KCXTD001),the 111 Project(grant D20008)Natural Science Foundation of Shandong Province of China(ZR2022MC001)the Scientific and Technological Projects of Qingdao(19‐6‐1‐94‐nsh).
文摘The co-occurrence of plasmid-mediated multidrug resistance and hypervirulence in epidemic carbapenem-resistant Klebsiella pneumoniae has emerged as a global public health issue.In this study,an ST23 carbapenem-resistant hyper-virulent K.pneumoniae(CR-HvKP)strain VH1-2 was identified from cucumber in China and harbored a novel hybrid plasmid pVH1-2-VIR.The plasmid pVH1-2-VIR carrying both virulence and multidrug-resistance(MDR)genes was likely generated through the recombination of a virulence plasmid and an IncFIIK conjugative MDR plasmid in clinical ST2318622 isolated from a sputum sample.The plasmid pVH1-2-VIR exhibited the capacity for transfer to the clinical ST11 carbapenem-resistant K.pneumoniae(CRKP)strain via conjugation assay.Acquisition of pVH1-2-VIR plasmid directly converted a CRKP into CR-HvKP strain characterized by hypermucoviscosity,heightened virulence for Galleria mellonella larvae,and increased colonization ability in the mouse intestine.The emergence of such a hybrid plasmid may expedite the spread of CR-HvKP strains,posing a significant risk to human health.
文摘Objective:To observe the effect of moxibustion on the expression of N-methyl-D-aspartic acid(NMDA)receptor subtype 2B(NR2B)in the hippocampus of rheumatoid arthritis(RA)rats,and to explore the analgesic mechanisms of moxibustion in RA treatment.Methods:Sixty male Sprague-Dawley rats were randomly divided into a normal group,a model group,a moxibustion group,a moxibustion+NMDA receptor antagonist(AP-5)group,and a moxibustion+NMDA receptor agonist(NMDA)group,with 12 rats in each group.Except for the normal group,rats in the other four groups were treated with complete Freund's adjuvant in a windy,cold,and damp environment to replicate RA models.Rats in the moxibustion group received suspended moxibustion with moxa sticks at Shenshu(BL23)and Zusanli(ST36),and the two points were used alternately.After intraperitoneal injection of AP-5 or NMDA,rats in the moxibustion+AP-5 group and the moxibustion+NMDA group received the same moxibustion intervention as in the moxibustion group,once a day for 15 d.The thermal withdrawal latency(TWL)of rats in each group was detected before and after modeling and after the 15-day intervention.After the 15-day intervention,hematoxylin-eosin staining was performed to observe the pathological changes in knee joints.The real-time fluorescence quantitative polymerase chain reaction method was used to detect the mRNA expression of NR2B in the hippocampus;Western blotting assay was used to detect the protein and the phosphorylated protein expression of hippocampal NR2B.Results:The synovial tissue was proliferated,the synovial lining was significantly thickened,the pannus was formed,and the cartilage and bone tissues were significantly damaged in the model group.After intervention,the pathological morphology of the knee joints in the moxibustion group,the moxibustion+AP-5 group,and the moxibustion+NMDA group was significantly improved,and the improvement in the moxibustion+AP-5 group was more notable than that in the moxibustion+NMDA group.Compared with the normal group,the TWL was significantly decreased(P<0.01),and the mRNA,protein,and phosphorylated protein expression levels of hippocampal NR2B were significantly increased in the model group(P<0.01).Compared with the model group,the TWL of each intervention group was significantly increased(P<0.01 or P<0.05),and the mRNA,protein,and phosphorylated protein expression levels of hippocampal NR2B were significantly decreased(P<0.01).Compared with the moxibustion group,the TWL was significantly increased(P<0.01),and the mRNA,protein,and phosphorylated protein expression levels of hippocampal NR2B were significantly decreased in the moxibustion+AP-5 group(P<0.01);the TWL was significantly decreased(P<0.01),and the mRNA,protein,and phosphorylated protein expression levels of hippocampal NR2B were significantly increased in the moxibustion+NMDA group(P<0.01).Conclusion:Moxibustion reduces hyperalgesia in RA inflammatory rats.The analgesic effect may be related to the decrease in the expression and phosphorylation levels of NR2B in the hippocampus.
