ABSTRACT
Objective To investigate the effects of angiotensin Ⅱ (Ang Ⅱ) or high glucose on the toll-like receptor 4 (TLR4) expression,inflammatory cytokines and fibrotic factors in human tubular epithelial cells (HK-2),revealing the innate immune-related pathogenesis of diabetic nephropathy (DN) which may have clinical implications.Methods Three TLR4 siRNA sequences were designed and synthetized.After transfection,the most effective siRNA was selected to use for further expriments.The experiment consisted of 2 parts.Part 1:Cells were divided into three groups:normal-glucose group (NG,5.5mmol/L glucose),mannose group (M,5.5 mmol/L glucose + 19.5 mmol/L mannose),High-glucose group (HG,25 mmol/L glucose),preliminary validated the effects of high glucose and high osmotic pressure.Part 2:Cells were divided into seven groups:NG group,HG group,Ang Ⅱ group,Ang Ⅱ + negative group,HG+ negative group,Ang Ⅱ + siRNA group and HG+ siRNA group.Real time PCR was used to analyze the mRNA expression of TLR4,myeloid differentiation factor 88 (MyD88),heat shock protein 47 (HSP47).Western blotting was used to observe the protein expression of TLR4,MyD88,HSP47,NF-κB,type Ⅳ collagen (ColⅣ).ELISA was used to detect the expression of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6).Results Compared with NG group,TLR4,MyD88,HSP47 mRNA and TLR4,MyD88,NF-κB,ColⅣ,HSP47 protein were highly expressed under high glucose or Ang Ⅱconditions (P ＜ 0.01),and the expression levels of MCP-1 and IL-6 also increased significantly (P ＜ 0.01).Compared with HG or Ang Ⅱ group,the above indicators were obviously inhibited in the TLR4 siRNA groups (P＜0.01).Comparison between blank vector transfected groups and HG group as well as Ang Ⅱ group indicated no statistic significance (P ＞ 0.05).Conclusions Both Ang Ⅱ and high glucose stimulate TLR4 expression,which result in the up-regulation of inflammatory and fibrotic factors in HK-2.Specific target of TLR4 gene silencing can block the TLR4 pathway that is activated by high glucose and Ang Ⅱ,and thus reduce the inflammatory and fibtogenic factors' release.TLR4 signal is the common innate immune response pathway which induces the release of inflammatory and fibrotic factors in HK-2 under high glucose or high angiotension conditions.
ABSTRACT
Based on a review of research and application of the clinical decision support system (CDSS) at home and abroad,a KB-CDSS building model is proposed.The authors rounded up the architecture,principle,process,construction of the knowledge base,system design and application value of the system.In the end,the paper introduced the application of WanFang Data Clinical Diagnosis and Treatment Knowledge Base.
ABSTRACT
Many medical journals have already digitalized their publishing procedure,but not achieved digital publishing yet.Utilizing digital technology,digital publishing can achieve the functions that paper media cannot,such as information storage,fast search,real-time publishing,individualized information and interaction with readers.These functions entail digitalization of medical journals,and involve a range of macro- and micro-modifications,including laws,industry policies,personnel training,and culture development.There is a long way to go for Chinese medical journals to enter the stage of digital publishing.
ABSTRACT
To investigate the effect of selective N-methy-D-aspartate receptor antagonist MK-801 on dentate granule cell neurogenesis after diffuse brain injury in the adult rat, so as to explore the role of glutamic acid on dentate granule cell neurogenesis after diffuse brain injury. 45 adult male SD rats were subjected to diffuse brain injury and randomized into MK-801-treatment group, vehicle-treatment group and control group (n=15 each). By using bromodeoxyuridine ( BrdU ) labelling method and immunohistochemistry to observe dividing cells, the proliferation rates of neural precursor cells in the dentate gyrus(DG) were compared between MK-801-treatment group and corresponding control groups on 2, 4, 6, 8, and 12 days after diffuse brain injury. The results showed that MK-801 (1mg/kg i.p.) significantly reduced the number of BrdU labeled cells in the dentate gyrus on 4, 6, 8 and 12 days after diffuse brain injury (P