63 normal human gallbladders (non-stone group) and 47 inflammed cholesterol stone gallbladders(stone group) were assayed for the amount of macrophages(ΜΦ),the levels of tumor necro-sis factor (TNF) and interleukin 1(1L-1).It was found that in stone group,the amount of ΜΦ was significantly higher than in non-stone group(ΜΦ4101.90±295.72 vs 572.13±30.07AU,Plt;0.01).The levels of TNF and 1L-1 released mainly from the MΦ in stone group were also significantly increased in comparison with those in non-stone group(TNF 18.12±2.03 vs 4.45±0.39ng/mg,Plt;0.001;1L-1 102.42±7.84 vs 66.75±9.50u/mg protein,Plt;0.05).These results suggest that the activited ΜΦ and increases of TNF,1L-1 may be closely related to the inflammatory reaction in gallbladders and the formation of cholesterol gallstones.
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.
ObjectiveTo summarize the current advancement of peroxisome proliferator activated receptors (PPARs) participating in formation of abdominal aortic aneurysm (AAA) and to find out the potential treatment strategy of AAA. MethodsRelevant literatures about PPARs and formation of AAA were reviewed. ResultsAAA involved inflammation of all the layers of aorta, and the formation of AAA needed many kinds of inflammatory cells and cytokines. Many researches in vitro or in vivo had shown that PPARs could reduce the expression of inflammatory cytokines, to reduce formation of AAA. However, PPARγ was also confirmed to participate in the formation of AAA and the mechanism might be the transformation of macrophage from type 1 macrophage (M1) to type 2 macrophage (M2). According to the existing studies, the assumption could be that PPARγ can suppress the inflammatory function of M1 to reduce formation of AAA at the initiating stage, and promote formation of AAA by inducing the transform of macrophage to M2 at the late stage. ConclusionPPARs may be a potential targeting point for the prevention of AAA. More studies are needed to show the feasibility and to decide the application timing.
Objective To observe the change of diffusion upper limit of macromol ecules through pathological retina and the difference between the layers of retina. Methods Retinal edema was emulated by establishing branch retinal vein occlusion (RVO) model in miniature pig eyes under photodynamic method. Two days later, the retinas of both eyeballs were peeled off. The diffusion test apparatus was designed by ourselves. FITC-dextrans of various molecular weights (4.4, 9.3, 19.6, 38.9, 71.2 and 150 kDa) and Carboxyfluorescein (376 Da) were dissolved in RPMI1640 solutions and diffused through inner or outer surface of retina. The rate of transretinal diffusion was determined with a spectrophotometer. Theoretical maximum size of molecule (MSM) was calculated by extrapolating the trend-linear relationship with the diffusion rate. In separate experiments to determine the sites of barrier to diffusion, FITC-dextrans were applied to either the inner or outer retinal surface, processed as frozen sections, and viewed with a fluores cence microscope. Results FITC-dextrans applying to inner retinal surface, 4.4 kDa dextrans were largely blocked by inner nuclear layer (INL); 19.6,71.2 kDa dextrans were blocked by the nerve fiber layer (NFL) and inner plexiform layer; 15.0 kDa dextrans were blocked by NFL. FITC-dextrans applying to outer retinal surface, most dextrans with various molecular weights were blocked before outer nuclear layer (ONL). No matter applying to the inner or outer surface, Carboxyfluore scein can diffuse through the whole retina and aggregate at INL and ONL. After RVO, the inner part of retina became edema and cystoid, loosing the barrier function. Compared with the normal retina, the MSM in RVO tissues increased (6.5plusmn;0 39nm Vs 6.18plusmn;0.54nm, t=4.143, P=0.0001). Conclusions A fter RVO, the barrier function of inner part of retinal is destroyed and the upper limit of diffusion macromolecule size increased, which is nevertheless limited. ONL acts as bottle-neck barriers to diffusion, if the outer part of retina is damaged, the change of the diffusion upper limit will be prominent. （Chin J Ocul Fundus Dis，2008，24：197-201）
The SAS is considered as internationally-known standard software in the field of data processing and statistics, which is also excellent in conducting meta-analysis; however, it require users to have higher technical expertise due to its complex and difficult program coding. Assessing statistical power calculation of significance tests is one of important steps in meta-analysis. Guy Cafri et al., developed a macro (%metapower) for well implement this calculation in SAS. This macro is specifically designed to implement the statistical power calculation of overall results of meta-analysis, heterogenity, and subgroup analysis, which is easy to operate. This article introduces%metapower based on examples.
Objective To overview the systematic reviews about the efficacy and safety of respiratory fluoroquinolones for community-acquired pneumonia (CAP). Methods We electronically searched databases including China National Knowledge Internet, WanFang Data, VIP, PubMed, Embase and The Cochrane Library to collect systematic reviews or Meta-analyses about respiratory fluoroquinolones for CAP from inception to November 2, 2017. Two reviewers independently screened literatures, extracted data, and then AMSTAR tool was used to assess the methodological quality of included studies. Results A total of 18 systematic reviews/Meta-analyses were included. The results of quality assessment indicated the scores ranged from 5 to 10. Among the 11 items, the item 1 of " Was an ‘a priori’ design provided” and item 4 " Was the status of publication (i.e. grey literature) used as an inclusion criterion” appeared to be the most problematic. The results of overview suggested that: the efficacy of respiratory fluoroquinolones might be similar to β-lactams plus macrolides combination treatment for CAP. However, respiratory fluoroquinolones might be more safety. In addition, the efficacy of respiratory fluoroquinolones sequential therapy for CAP was similar to that of continuous intravenous therapy, but the adverse reactions of the former were fewer. Conclusions Respiratory fluoroquinolones might be similar in efficacy for CAP to other antibiotics recommended by the guidelines with less adverse reactions. However, it can increase multi-drug resistance and potential tuberculosis drug resistance, we should strictly follow the principle of rational use of antibiotics to avoid abuse.
ObjectiveTo investigate the role of Krüppel-like factor 4 (KLF4) mediated monocyte/macrophage subtype switch in the pathological progression of pulmonary fibrosis.MethodsThirty-six patients with interstitial pneumonia were recruited from Characteristic Medical Center of the Chinese People's Armed Police Force between May 2015 and January 2017. Peripheral venous blood and bronchoalveolar lavage fluid were collected in the morning. Pulmonary function and arterial blood gas were tested after admission. Flow cytometry was used to test monocyte subtypes of peripheral blood and macrophage subtypes of bronchoalveolar lavage fluid. KLF4 of peripheral blood was detected by enzyme linked immunosorbent assay. Thirty normal subjects were selected as control group of peripheral blood mononuclear cell subtypes and KLF4 (control group A), and 10 patients without pulmonary fibrosis who needed bronchoscopy were selected as control group of macrophage subtypes in alveolar lavage fluid (control group B). The relationship between the expression of KLF4 and the differentiation of monocytes and macrophages were observed. Furthermore, the relationship between the differentiation of monocytes subtypes, macrophages subtypes and lung function were observed.ResultsMonocyte of CD14++CD16– subtype in pulmonary fibrosis group was significantly lower than that in control group A (P<0.05). Monocyte of CD14++CD16+ subtype in pulmonary fibrosis group was significantly higher than that in control group A (P<0.05). No significant difference was found between the two groups regarding CD14+CD16++. No correlation was found between three subtypes of monocyte and DLCO of patients and between three subtypes of monocyte and PaO2 of patients. M1 macrophage in pulmonary fibrosis group was significantly lower than that in control group B (P<0.05). M2 macrophage in pulmonary fibrosis group was significantly higher than that in control group B (P<0.05). Negative correlation was found between the ratio of M2 subtypes and DLCO of patients and between the ratio of M2 subtypes and PaO2 of patients (P<0.05). KLF4 protein of blood in pulmonary fibrosis group was significantly higher than that in control group A (P<0.05). Positive correlation was found between the ratio of M2 subtypes and KLF4 protein (P<0.05).ConclusionsCD16+ monocyte plays a role in the occurrence and development of pulmonary fibrosis, but no evidence is found there is a direct correlation between monocyte subtypes of peripheral blood and fibrosis degree of lung tissue. M2 macrophage subtype plays an important role in the development of interstitial pneumonia. The number of M2 macrophages is positively correlated with the severity of pulmonary fibrosis. Monocyte/macrophage subtype differentiation by KLF4 may play a role in the pathological progression of pulmonary fibrosis.
Objective To study the effect of mechanical stretch on the microenvironment of BEAS-2B on macrophage polarization and the role of polarized macrophages in the epithelial-mesenchymal transition (EMT) of BEAS-2B. Methods Using enzyme linked immunosorbent assay to detect the changes in the levels of cytokines such as interferon-γ, granulocyte-macrophage colony stimulating factor, tumor necrosis factor-α, interleukin (IL)-4, IL-6, IL-10 in the supernatant of lung epithelial cells cultured statically and mechanically stretched. The M0 macrophages (derived from THP-1) were stimulated by stretch/static conditioned medium of BEAS-2B. The surface markers of M1 (CD197) /M2 (CD206) macrophages were detected by flow cytometer. Stretch/static conditioned medium were used to stimulate the co-culture system of macrophages and BEAS-2B in the presence or absence of platelet-derived growth factor receptor inhibitor (PDGFRi), then the protein expression level of EMT makers was examined by Western blot. Results Exposure of BEAS-2B to mechanical stretch resulted in significantly higher production of the pro-M1/M2 polarized factor. The EMT of the co-culture system of M0 and BEAS-2B could be induced by stretch conditioned medium, epithelial marker cytokeratin (CK)-8 and E-cadherin were decreased, while mesenchymal marker α-smooth muscle actin, N-cadherin and vimentin were increased in stretch conditioned medium group. The expression of platelet-derived growth factor (PDGF) was significantly higher in stretch conditioned medium group. The PDGFRi can block the EMT in stretch conditioned medium group. Conclusions The lung epithelial cell supernatant induced by mechanical stretch can promote the polarization of macrophages to M1 and M2. Polarized macrophages promote EMT in human lung epithelial cells via PDGF, and blocking PDGF might attenuate the VILI-associated lung fibrosis.
Macrophages are major effecter cells of nonspecific immune response, the polarization of which plays a great role in inflammation, repairing and angiogenesis. According to functional phenotypes, macrophages can be polarized to classically activated type (M1), which could promote angiogenesis, and alternatively activated type (M2), which could inhibit angiogenesis. The proportion of M1/M2 could modulate the growth of choroidal neovascularization (CNV). Under the conditions of aging and injury within the retina, macrophages may polarize to M2, which could generate several proangiogenic factors, initiating and promoting the formation of angiogenesis and fibrous scar. Therefore, regulation of macrophage polarization is expected to inhibit angiogenesis and provide new insight for treatment of CNV.