1.Metabolism of high density lipoprotein and the research progress of its effects on sepsis
Meiyun LIU ; Huanping ZHOU ; Xin LYU
Chinese Critical Care Medicine 2017;29(4):377-380
Sepsis is a high-risk factor for the death of critical patients. High density lipoprotein (HDL) are the major protective serum proteins, and the serum levels of HDL are closely related to the severity of sepsis. The anti-inflammatory and anti-oxidation properties of HDL, may be able to play an important role in the innate immune response. Thereby it may reduce the damage of septic shock and multiple organ dysfunction syndrome (MODS) in animals or human beings, and improve the prognosis. In order to unveil the metabolism of HDL in septic patients and its effects on both progression and prognosis of sepsis, this review not only focuses on the composition and structure of HDL, but also analyzes its pivotal role in inflammatory immune response and anti-oxidation.
2.Preparation of a fusion protein with pneumococcal surface protein A of two different clades of familyⅠand analysis of immunogenicity of the recombinant protein
Haiying LIN ; Yonghui PENG ; Shuangling ZHANG ; Chunhua LUO ; Meiyun ZHENG ; Wei LYU ; Duqing ZHAN
Chinese Journal of Microbiology and Immunology 2015;(5):377-381
Objective To construct a recombinant fusion protein with pneumococcal surface pro-tein A (PspA) of Stretococcus pneumonia (SPN) familyⅠclade 1 and 2, and to analyze the immunogenici-ty of the fusion protein.Methods The gene fragments encoding theα-helix of PspA of the two clades were amplified by PCR and then inserted into the expression vector pET-27b(+) to construct the recombinant ex-pression plasmid.The transformed Escherichia coli BL21 strains carrying expression plasmid were induced by IPTG to express the recombinant protein.The titers and affinity of antibodies against PspA protein were measured by ELISA.An opsonophagocytic assay and an animal experiment were performed to evaluate the immunogenicity of the recombinant protein.Results Double enzyme cutting and gene sequencing confirmed the two purpose gene fragments were correctly expressed in the expression vector pET-27b(+).The titers of anti-PspA antibody in the serum of Kunming ( KM) mice immunized with the fusion protein were 1 ×104 . The affinity of anti-PspA antibody reached to 2×105 .The rates of recombinant PspA6B-PspA05 protein me-diated phagocytosis for SPN6B, SPN05 and SPN01 strains were 20%, 15% and 8.8%, respectively.No SPN23F strain was engulfed by macrophages upon the stimulation with PspA6B-PspA05 protein.The survival rates of mice injected with SPN05, SPN6B, SPN01 and SPN23F strains were respectively 75%, 92%, 75%and 33%upon the immunization of PspA6B-PspA05 protein.Conclusion The recombinant fusion protein PspA6B-PspA05, constructed with the PspA proteins of Stretococcus pneumonia familyⅠclade 1 and 2, was successfully expressed in the E.coli prokaryotic system with the advantage of high immunogenicity.High ti-ters of anti-PspA antibodies with high specificity were induced in KM mice upon the stimulation with Ps-pA6B-PspA05 protein.Moreover, a cross-protective immunity was induced in KM mice upon the immuniza-tion with PspA6B-PspA05 protein.
3.Influencing factors of hemorrhagic transformation and clinical outcomes in acute ischemic stroke after mechanical thrombectomy
Yuanyuan ZHANG ; Hongzhi ZHOU ; Meiyun LYU ; Qiuhong JI ; Ziyang GAO ; Shuhong LIU ; Yunfeng ZHANG
International Journal of Cerebrovascular Diseases 2016;24(10):882-886
Objective To investigate the risk factors for hemorrhagic transformation (HT) and poor outcomes in patients with acute ischemic stroke after mechanical thrombectomy.Methods The patients with acute ischemic stroke received mechanical thrombectomy were enrolled retrospectively.The demography,vascular risk factors and other clinical data of the patents were collected.The modified Rankin scale (mRS) was used to evaluate the clinical outcomes at day 90.Good outcome was defined as mRS score 0-2.The patients were divided into either a HT group or a non-HT group according to their HT conditions.Multivariate logistic regression analysis was used to identify the independent risk factors for HT and poor outcomes.Results A total of 48 patients with acute ischemic stroke received mechanical thrombectomy were enrolled,including 25 males (52.1%).Their mean age was 64.77± 9.14 years.The mean National Institutes of Health Stroke Scale (NIHSS) score was 17.70 ± 3.77.Twenty-two patients (45.8%) occured HT,of which 9 were symptomatic HT;24 (50.0%) had good outcomes.The proportion of males in the HT group was significantly lower than that in the non-HT goup (30.4%vs.72.0%;x2 =8.293,P =0.004),while the proportions in patients with diabetes (65.2% vs.36.0%;x2 =4.090,P =0.043) and atrial fibrillation (78.3% vs.44.0%;x2 =5.880,P =0.015),as well as the baseline fasting blood glucose level (8.514 ± 4.400 mmol/L vs.6.354 ± 1.472 mmol/L;t =2.319,P =0.025) were significantly higher than those in the non-HT group.Multivariate logistic regression analysis showed that the atrial fibrillation (odds ratio [OR] 6.136,95% confidence interval [CI] 1.617-23.291;P =0.042) was a risk factor for the occurrence of HT after mechanical thrombectomy.The proportion of diabetic patients (29.2% vs.70.8%;x2 =8.333,P=0.04) and baseline NIHSS score (16.050±4.865 vs.19.210±4.423);t=2.310,P=0.026) of the good outcome group were significantly lower than those of the poor outcome group,while the proportions of patients in atrial fibrillation (75.0% vs.45.8%;x2 =4.269,P =0.039),anterior circulation stroke (87.5% vs.62.5%;x2 =4.000,P =0.046) middle cerebral artery (75.0% vs.29.2%;x2 =10.113,P =0.006),vertebral basilar artery (37.5% vs.12.5%;x2 =10.113,P =0.006) occlusion and parenchymal hematoma (33.3% vs.4.1%;P=0.011) were significantly higher than the poor outcome group.Multivariate logistic regression analysis showed that diabetes (OR 5.898,95% CI 1.699-20.479;P=0.005),baseline NIHSS score (OR 1.167,95% CI 1.011-1.347;P =0.035),and parenchymal hematoma (OR 1.295,95% CI 1.099-1.875;P=0.028) were the independent risk factors for poor outcomes.Conclusions Atrial fibrillation is an independent predictor of HT risk in patients with acute ischemic stroke after mechanical thrombectomy.Diabetes mellitus,higher baseline NIHSS score,and concurrent brain parenchymal hematoma are the independent predictors of poor outcomes.Therefore,the risk of HT and adverse outcomes should be fully assessed before mechanical thrombectomy in patients with acute ischemic stroke.
4.Research progress of mesenchymal stem cells in the treatment of ALI
Huanping ZHOU ; Meiyun LIU ; Xin LYU
Chinese Critical Care Medicine 2017;29(11):1039-1042
Acute lung injury (ALI) is one of the most common clinical critical illnesses. Its severe stage is acute respiratory distress syndrome (ARDS), characterized by rapid onset and high mortality. There is no effective treatment. Based on many preclinical studies, mesenchymal stem cells (MSCs) have great potential as a therapeutic strategy for ALI, clinical trials are underway, and studies on the therapeutic effects of MSCs progressively deep into the molecular mechanism and continue to make new progress. However, the use of MSCs, their specific methods and risks, especially on the risk of iatrogenic tumor formation remains unresolved. In this paper, we reviewed the main problems in the application of MSCs in the treatment of ALI and the main problems in the application of MSCs in order to explore the feasibility and future direction of MSCs in the treatment of ALI.
5.Research progress of metabolism reprogramming in regulating macrophage polarization
Meiyun LIU ; Pengcheng ZHANG ; Xin LYU
Chinese Critical Care Medicine 2020;32(6):765-768
Macrophages are important innate immune cells that play essential roles in the inflammatory response. The phenotypic plasticity of macrophages enables them to be polarized into distinct gene phenotypes under different immune microenvironments to regulate the process of inflammation. The study of macrophage metabolic reprogramming aims to clarify the influence of key metabolic pathways on the regulation of different polarization states and related functions of macrophages. This review focuses on the relationship between the four key metabolic pathways [glycolysis, tricarboxylic acid (TCA) cycle, fatty acid metabolism and amino acid metabolism] and the distinct gene phenotypes of macrophages. It also reveals the metabolic regulation of the immune function of macrophage cells thus to provide new ideas and methods for the study of macrophage polarization-related process of inflammation.
6. Research progress in glycogen metabolism reprogramming in sepsis associated immune cells
Danyang WANG ; Meiyun LIU ; Xin LYU
Chinese Critical Care Medicine 2019;31(9):1167-1169
Metabolic reprogramming is the response of cells to environmental changes, such as cell activation, proliferation and differentiation, which involves changes in metabolism-related enzymes, metabolites and metabolic pathways. Sepsis-associated immune cells undergo metabolic reprogramming in response to inflammatory signals, which not only provides biological energy and biosynthesis requirements, but also determines cell fate and function in a highly specific way. In this paper, the changes in glycolysis, tricarboxylic acid cycle, oxidative phosphorylation and other glucose metabolism pathways of macrophages, T lymphocytes, dendritic cells, neutrophils and other sepsis related immune cells are described, so as to provide feasibility for future research and metabolic therapy.