Objective To explore the role of macrophage-stimulating protein ( MSP) and receptor tyrosine kinase RON in the airway inflammation of chronic obstructive pulmonary disease( COPD) , and investigate its possible mechanism. Methods The rat COPDmodel was established by exposing the rats to cigarette smoke daily for three months. Rat alveolar macrophages ( AMs) were isolated in vivo and cultured,and then challenged with different concentrations of MSP for 24 hours. The concentrations of MSP in broncho-alveolar lavage fluid ( BALF) and serum, and the levels of IL-1β, TNF-α, IL-8, and IL-10 in the supernatants were measured by ELISA. The expression of RONmRNA in lung tissue was assessed by reverse transcription-polymerase chain reaction. The levels of RON protein in the lung tissue and AMs cultured in vitro were observed by immunohistochemistry. The activity of superoxide dismutase ( SOD) and malondialdehyde ( MDA) content in the culture solution were measured with chromatometry method. Results Compared with the control group, the concentrations of MSP in serum and BALF of the COPD rats were significantly higher ( P lt;0. 01) . The levels of RONmRNA and RON protein in the COPD rats were also upregulated significantly ( P lt; 0. 01) . MSP evoked the AMs isolated from the normal and COPD rats to generate more content of MDA and caused a reduction in activity of SOD. In addition, MSP stimulated TNF-α, IL-8, IL-1βand IL-10 release fromAMs of the normal and COPD rats dose-dependently. The levels of TNF-α, IL-8, and IL-1βwere higher, while the level of IL-10 and the SOD activity were lower in AMs of the COPD group than those of the control group in the same dose of MSP ( P lt;0. 01) . The more significant increase in the levels of TNF-α, IL-8, IL-1β, and the more notable decrease in the activity of SOD was found in the COPD group compared with the control group. But the degree of increasing MDA and IL-10 in the AMs of the COPD group was lower than that in the control group. Linear correlation analysis showed that the MSP concentration and the RON protein level in the COPD rats were positively associated with the total cellcounts and AM counts in BALF, and were related to the indexes for pulmonary emphysema. Conclusions There is a close correlation between the MSP and receptor tyrosine kinase RON with the airway inflammation of COPD. The mechanism might be that MSP promote the macrophages release inflammatory factors and increase the production of oxygen free radicals.
Objective To observe the changes of soluble triggering receptor expressed on myeloid cell-1 ( sTREM-1) and inflammatory mediators levels in plasma of severe pneumonia patients, and explore the significance of systemic inflammatory response state.Methods Plasma levels of sTREM-1, tumor necrosis factor-α ( TNF-α) and interleukin-10 ( IL-10) were examined in 40 patients with severe pneumonia, 25 patients with uncomplicated pneumonia, and 15 healthy volunteers. Plasma levels of TNF-α,IL-10 and sTREM-1 in survival and non-survival severe pneumoniawere observed on days 1,4, 7 and the day of discharge or death.Results Plasma levels of TNF-α, IL-10, and sTREM-1 [ ( 44. 25 ±10. 81) pg/mL,( 58. 21 ±16. 41) pg/mL, ( 51. 75 ±18. 51) pg/mL, respectively] in the patients with severe pneumonia were higher than those with uncomplicated pneumonia [ ( 24.6 ±6. 45) pg/mL, ( 24. 56 ±7. 1) pg/mL,( 25. 55 ±7. 72) pg/mL, respectively] and the normal controls [ ( 13. 82 ±4. 04) pg/mL, ( 15. 30 ±4. 45)pg/mL, ( 14. 37 ±4. 82) pg/mL, respectively] ( P lt;0. 001) . Plasma levels of TNF-α, IL-10, and sTREM-1 were gradually decreased in the survivors, while maintained at high levels or increased in the non-survivors.The levels of these mediators were all significantly higher in the non-survivors than the survivors at all time points. The ratio of TNF-α/ IL-10 level was higher in the severe pneumonia patients than the uncomplicated pneumonia patients and the control subjects ( 1. 286 ±0. 177 vs. 1. 077 ±0. 410 and 0. 932 ±0. 154) on day 1.The ratio of TNF-α/IL-10 level was higher in the non-survivors than the survivors at all time points. There was negative correlation between plasma levels of sTREM-1 and TNF-αon day 1 ( r = - 0. 479, P =0. 002) ,and positive correlation between plasma levels of sTREM-1 and IL-10 on day 1 ( r = 0. 326, P = 0. 040) .Conclusions There are excessive release of inflammatory mediators and unbalanced systemic inflammatory response in patients with severe pneumonia, especially in non-survivors. sTREM-1, TNF-α and IL-10 are involved in the inflammatory response, and their levels may reflect the prognosis.
【Abstract】ObjectiveTo explore the mechanisms of anabolism intensified by recombination human growth hormone (GH) on the basis of total parenteral nutrition (TPN) during postoperative in gastrointestinal carcinoma patients. MethodsNinety-four gastrointestinal carcinoma patients undergone operation were randomly divided into TPN group and TPN+GH group. The levels of TNF-α, IL-1, IL-6 and CRP were detected in the first, third, seventh postoperative day. ResultsThe levels of TNF-α, IL-1, IL-6 and CRP were significantly lower in TPN+GH group than those in the TPN group at the first, third, seventh postoperative day （P＜0.01）. The levels of TNF-α, IL-1, IL-6 and CRP were significantly higher at the indicated time of postoperative days than the pre-operative days in the two groups (P＜0.01）. ConclusionBy inhibiting TNF-α, IL-1, IL-6 and CRP production in gastrointestinal carcinoma patients undergone operation and blocking high catabolism induced by inflammatory cytokines, GH promotes the synthesis of anabolism.
Objective To introduce the inflammatory microenvironment and epithelial-mesenchymal transition process of hepatocellular carcinoma, and review the relationship between them. Methods Domestic and international literatures were collected to summary the relationship between epithelial-mesenchymal transition and the inflammatory microenvironment of hepatocellular carcinoma. Result Many inflammatory factors and viral gene encoding proteins in the inflammatory microenvironment play an important role in the process of epithelial-mesenchymal transition in hepatocellular carcinoma. Conclusions The inflammatory microenvironment of hepatocellular carcinoma is an indispensable role in the process of epithelial-mesenchymal transition. The inhibition and treatment of inflammatory microenvironment may play a more active role in the control of tumor invasion and metastasis.
ObjectiveTo bioinformatically analyze the gene chip data of chondrocytes from osteoarthritis patients from the Gene Expression Omnibus (GEO) database, and explore the molecular mechanisms of osteoarthritis.MethodsWe searched the GEO database (up to April 23rd, 2021) for data of chondrocytes and gene expression profiling in human knee osteoarthritis via the key words of “osteoarthritis OR cartilage OR chondrocyte*”. Then, we selected the samples by our inclusion criteria. The data were normalized before analysis. After differentially expressed genes were identified, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, Search Tool for the Retrival of Interacting Genes/Proteinsm, R language, Perl language, Cytoscape software, and DAVID database were used to perform differentially expressed gene analysis, functional annotation, and enrichment analysis.ResultsThe differentially expressed genes were mostly enriched in cell components and some extracellular regions, which participated in cell division, mitosis, cell proliferation and inflammatory response mainly via the regulation of protein kinase activity. The differentially expressed genes were mainly involved in the cell proliferation signaling pathway, mitogen-activated protein kinase signaling pathway, oocyte meiosis, cell cycle and so on.ConclusionsMultiple signaling pathways are involved in the changes of chondrocytes in human knee osteoarthritis, mainly about cell cycle and protein metabolism genes/pathways. Inflammatory factors and cytokines may be the most important links in the pathogenesis of osteoarthritis.
Objective To investigate the difference of anticoagulant efficacy of heparin and citric acid during continuous renal replacement therapy (CRRT) in patients with severe acute pancreatitis, and analyze their effects of on filter life span, length of hospital stay and mortality. Methods Patients with severe acute pancreatitis in Intensive Care Unit of the First Affiliated Hospital of Hebei North University between January 2018 and July 2022 were retrospectively enrolled, and they were divided into heparin group (control group) and citric acid group (research group) according to anticoagulation methods. The differences of anticoagulant catheter blockage during CRRT, filter life span, length of hospital stay, and 90-day mortality between the two groups were analyzed. Results A total of 108 patients were enrolled, including 56 in the research group and 52 in the control group. In pre-CRRT treatment, the balance value of fluid intake and outflow in the research group was significantly lower than that in the control group (P<0.05). The 108 patients received 217 times of CRRT treatment totally, with a median length of treatment of 63 h (range 44-87 h). The severity of catheter blockage in the research group was lower than that in the control group (P=0.003). The filter life span was longer in the research group than that in the control group [42.5 vs. 29.0 h; hazard ratio=1.83, 95% confidence interval (1.23, 2.73), P<0.001]; in the comparison of 90-day mortality, there was no significant difference between the two groups (P>0.05). The mean use of filters in the research group was less than that in the control group (1.93±0.09 vs. 2.17±0.14, P<0.001). The downtime of CRRT due to filter life in the research group was obviously shorter than that in the control group [120 (0, 720) vs. 300 (0, 890) min, P=0.029], while the duration of CRRT in the research group was remarkably better than that in the control group [10.6 (4.9, 27.7) vs. 8.1 (3.6, 25.0) d, P=0.024], and the risk of filter replacement due to special conditons in the research group was lower than that in the control group (46.4% vs. 65.4%, P=0.048). There was no statistically significant difference in the length of intensive care unit hospitalization or total hospitalization between the two groups (P>0.05). Conclusion Both heparin and citric acid could assist the treatment of CRRT, while citric acid might be apt to improve local coagulation and systemic inflammatory response.
Objective To study the effect of interleukin-6,10 (IL-6,10), C-reactive protein (CRP), and fibrinogen (FIB) on inflammatory response of lower limbs deep vein thrombosis (DVT). Methods Thirty patients with acute lower limb DVT (DVT group) and 30 volunteers (normal control group) were included in this study, and then the concentrations of serum IL-6, IL-10, CRP, and FIB were detected. Results The concentrations of serum IL-6, IL-10, CRP, and FIB of patients in DVT group before treatment were higher than those in normal control group (Plt;0.001). Compared with before treatment, the concentrations of serum IL-6, CRP, and FIB of patients after treatment were lower in DVT group (Plt;0.001), however, the concentration of serum IL-10 was higher (Plt;0.001). There was no difference of the concentrations of serum FIB between DVT group after treatment and normal control group (Pgt;0.05), but the concentrations of serum IL-6, IL-10, and CRP of patients in DVT group after treatment were higher than those in normal control group (Plt;0.05). Conclusion Inflammatory factors may involve in DVT. Therein IL-6, CRP, and FIB play important roles in acute stage of DVT, and IL-10 may have an anti-inflammatory effect.
Objective To investgate the expression of p38 mitogen-activated protein kinase （p38MAPK） in lung tissue of rats with severe acute pancreatitis （SAP）， and to explore the relationship between p38MAPK and pulmonary capillary barrier injury. Methods Forty male and healthy Sprague-Dawley （SD） rats were randomly （random number method） divided into sham operation （SO） group and SAP group， then rats of SAP group were sub-divided into 3， 6， 12， and 24 h group， each group enrolled 8 rats， respectively. SAP model rats were established by injecting 5% sodium taurocholate solution retrograde into the biliopancreatic duct. ELISA method was used to test the serum tumor necrosis factor-α （TNF-α） and interleukin-1β （IL-1β）， and pathological changes in lung and pancreas tissues were observed by HE staining. Immunohischemistry method was used to detect phosphorylated p38 （p-p38） protein and aquaporin 1 （AQP1） protein of lung tissues. The expression level of AQP1 mRNA was measured by quantitative real-time PCR. Results Hyperemia， edema， and inflammatory cell infiltration were observed in lung tissues， abundance of necrosis， part gland structure fuzzy or even disappear were observed in pancreas tissues of all 4 time point groups. Compared with SO group， levels of serum TNF-α and IL-1β were significantly higher in 4 time point groups （P＜0.05）. Lower expression level of p-p38 protein was detected in lung tissues of SO group， while in the early stage of SAP （SAP 3 h group）， the expression level of p-p38 protein significantly increased， which peaked in 6 h group and was still higher than SO group in 24 h group （P＜0.05）. Compared with SO group， the expression levels of AQP1 mRNA and protein were significantly lower in all 4 time point groups （P＜0.05）， which had negative correlation with the levels of serum TNF-α，IL-1β， and the expression level of p-p38 protein （r=-0.87， P＜0.05；r=-0.88， P＜0.05；r=-0.78， P＜0.05）. Conclusion The decrease of AQP1 protein in lung tissue is one of the vital causes for pulmonary capillary barrier injury in SAP， which probably works by the activation of p38MAPK and the excessive release of inflammatory cytokines.
ObjectiveTo explore the effects of simvastatin on the expression of matrix metalloproteinase (MMP) and inflammatory factors in rats with smoke-induced chronic obstructive pulmonary disease (COPD). Methods40 male Wistar rats were randomly divided into four groups, including a normal group (group A), a simvastatin group (group B), a COPD model group (group C) and a simvastatin intervention group (group D). The COPD model of the group C and D were induced through exposing to the cigarette smoke repeatedly. At the same time, the rats of group B and D were given by gavage 5 mg/(kg·d) with simvastatin, and the other two groups were given with the same volume saline for 16 weeks. Pulmonary function tests and pathological examination of the lung tissue were performed after the induction of COPD model. Enzyme-linked immunosorbent assay (ELISA) method was used to measure the content of MMP-2, MMP-9, IL-6, IL-8, TNF-α in lung tissue homogenate. ResultsThe airway resistance of group C and group D was significantly higher than the group A and group B (P<0.01), and the airway resistance of group D was significantly lower than group C (P<0.01). The degree of bronchial inflammation and emphysema of group C was more apparent than group D in the pathological section, and there were no bronchial inflammation and emphysema in group A and group B. The ELISA results showed that the contents of MMP-2, MMP-9, IL-6, IL-8, TNF-α in group C were all significantly higher than those in group D. ConclusionSimvastatin has inhibitory effect on pulmonary inflammation of COPD, and can reduce the expression of matrix metalloproteinase and inflammatory factors in the lung.