Objective To explore whether hospitalized elderly patients with severe communityacquired pneumonia ( SCAP) have better outcomes if they are treated with dual-therapy consisting of a β-lactam/macrolide or fluoroquinolone.Methods A prospective study was conducted in patients with SCAP aged 65 years or older between January 2007 and January 2012. These patients were assigned to a combination therapy group or a β-lactam monotherapy group by the attending physicians. Time to clinical stability( TCS) and total mortality were calculated. Prognostic factors for death were analyzed. Results Among the 232 patients, 153 patients were given β-lactam/macrolide or β-lactam/ fluoroquinolone ( macrolide in 67 patients and fluoroquinolone in 86) , while 79 were treated with β-lactam monotherapy. Compared with the monotherapy group, the combination therapy group was associated with significant decreased TCS ( median TCS, 10 days vs. 13 days) , and lower overall in-hospital mortality( 24.2% vs. 43.0%, P lt;0. 01) . Compared with fluoroquinolone, macrolide use was associated with lower ICU mortality ( 14.9% vs. 31.4% , P lt;0. 01) . Simplified acute physiology score Ⅱ, pneumonia severity index, mutilobar infiltration, and β-lactam monotherapy were confirmed as independent predictors of death. Conclusion β-lactam/macrolide or β-lactam/ fluoroquinolone combination therapy, especially with macrolide, has superiority over β-lactam monotherapy in elderly patients with SCAP, and should be recommended.
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.
Objective
To investigate the role of macrophage stimulating protein (MSP) in the pathogenesis of chronic obstructive pulmonary disease (COPD).
Methods
Ninety subjects were recruited from health examination center, outpatient or inpatient department in Affiliated Hospital of North Sichuan Medical College from July 2013 to December 2013. They were divided intoahealthy control group, a stable COPD group, and an acute exacerbation of COPD (AECOPD) group with 30 subjects in each group. The levels of MSP, interleukin-6 (IL-6), IL-8 and tumor necrosis factor-α (TNF-α) in the plasma of all subjects, as well as the levels of MSP in the induced sputum of the AECOPD and the stable COPD patients were assessed by enzyme-linked-immuno-sorbent assay.
Results
The concentrations of MSP, IL-6, IL-8 and TNF-α in the plasma of the patients with COPD were obviously higher than those of the healthy controls (P<0.05) while much higher in AECOPD patients than those in stable COPD patients (P<0.01).The concentration of MSP in the induced sputum of the patients with AECOPD was higher than that in the stable COPD patients (P<0.01). The concentrations of MSP in the serum and induced sputum as well as serum levels of IL-6, IL-8 and TNF-α in the patients with COPD were negatively correlated with the level of FEV1%pred. The concentrations of MSP in the serum and induced sputum in the COPD patients were positively correlated with the concentrations of IL-6, IL-8 and TNF-α.
Conclusions
The concentrations of serum and induced sputum MSP, and the serum concentrations of IL-6, IL-8 and TNF-α in COPD patients are related to the severity of the disease. MSP may play an important role in the pathogenesis of COPD. The mechanism might be mainly involved in the regulation of airway inflammation.
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）
Objective To explore the effects of several immunosuppressants on the cell numbers of cultured rat macrophages and Schwann’s cells. Methods The macrophages and Schwann’s cells were cultured from the newborn Wistar rats. Different concentrations of methylprednisolone(10-3, 10－4,10－6 and 10－8 mol/L), CsA(10－5, 10－6, 10－7 and 10－8 mol/L) and FK506(10-6, 10－7, 10－8 and 10－9 mol/L) were administrated to the cells, while control group was given no drugs. Twentyfour, 48 and 72 hours after administration, the cells from different concentrations were measured with MTT methods respectively. Theresults were compared and analyzed statistically. Results Only high concentration methylprednisolone (10-4 mol/L) and a certain range of concentrations of CsA (10-6，10-7 and 10-8 mol/L) and FK506 (10-7,10-8 and 10-9 mol/L) can provide protection to culturedrat macrophages. Under most concentrations, CsA and FK506 had no effects onthe cell number of cultured rat Schwann’s cell. Only with high concentration CsA (10-5 mol/L) and methylprednisolone (10-3 mol/L) could significantly decreased the cell number of Schwann’s cell. Long time (72 hours) and low dosage (10-8 mol/L) administration of methylprednisolone could significantlyprotect Schwann’s cell. Conclusion High concentration methylprednisolone and some certain concentration CsA and FK506 can protect cultured rat macrophages. But high concentration CsA and methylprednisolone prohibit the proliferation of Schwann’s cells. Only long time and low dosage methylprednisolonecan protect cultured rat Schwann’s cells.
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.
To compare the effectiveness of microdiscectomy and macrodiscectomy on the single-level lumbar disc protrusion (LDP). Methods Between November 2002 and October 2005, 241 patients with LDP underwent 2 surgical procedures: microdiscectomy (group A, 93 cases) and macrodiscectomy (group B, 148 cases). All patients had singlelevel LDP. In group A, there were 51 males and 42 females with an average age of 32.3 yeares (range, 18-47 years); there were 23cases of protrusion, 52 cases of prolapse, and 18 cases of sequestration with an average disease duration of 8.5 months (range, 1-18 months), including 8 cases at L2,3 level, 11 cases at L3,4 level, 35 cases at L4,5 level, and 39 cases at L5, S1 level. In group B, there were 81 males and 67 females with an average age of 31.8 years (range, 16-50 years); there were 37 cases of protrusion, 85 cases of prolapse, and 26 cases of sequestration with an average disease duration of 9.3 months (range, 1-20 months), including 9 cases at L2,3 level, 15 cases at L3,4 level, 63 cases at L4,5 level, and 61 cases at L5, S1 level. There was no significant difference in age, sex, segment level, type, or disease duration between 2 groups (P gt; 0.05). Results Immediate back and sciatic pain rel ief was achieved in 225 (93.4%) patients after operation. The satisfactory rates were 91.4% in group A and 87.8% in group B at 1 week after operation, showing no significant difference (P gt; 0.05). The length of incision, amount of bleeding, amount of drainage, and hospital ization time in group A were significantly fewer than those in group B (P lt; 0.05); while the operative time in group A was longer than that in group B, but showing no significant difference (P gt; 0.05). Dural laceration occurred in 4 cases of groupA and 5 cases of group B, superficial infections of incision occurred in 5 cases of group B and intervertebral space nfections occurred in 4 cases of group B, and epidural hematoma occurred in 1 case of group A. The perioperative compl ication rate (5.4%, 5/93) in group A was significantly lower (P lt; 0.05) than that in group B (9.5%, 14/148). LDP recurred in 4 cases (4.3%) of group A and in 9 cases (6.1%) of group B postoperatively, showing no significant difference (P gt; 0.05); of them, 11 cases received second operation and 2 cases were treated conservatively. All cases were followed up 36-77 months (mean, 51.4 months). There were significant differences in visual analog scale (VAS) and Oswestry disabil ity index (ODI) between 2 groups at the last follow-up and preoperation (P gt; 0.05), but there was significant difference in VAS at 1 week postoperatively between 2 groups (P lt; 0.05). VAS and ODI were obviously improved at 1 week and last follow-up when compared with preoperation (P lt; 0.05). There was no significant difference in the improvement rates of VAS and ODI between 2 groups at last follow-up (P gt; 0.05). According to cl inical evaluation of Modified Macnab criteria, the excellent and good rate was 90.3% in group A and 86.5% in group B at final follow-up (P gt; 0.05). Conclusion Both macrodiscectomy and microdiscectomy are effective for LDP, furthermore microdiscectomy is less invasive than macrodiscectomy. Microdiscectomy is recommended to treat single-level LDP.
Objectives To explore the expression of macrophage inflammatory protein-1beta (MIP-1β) in patients with none-small cell lung cancer (NSCLC) of different pathological types and its association with cancer clinical stages and metastasis of lymph nodes.Methods MIP-1β mRNA from fresh lung tissue of 38 NSCLC patients was amplified by RT-PCR and half-quantified.Immunohistochemical technique was performed to find out the expression of MIP-1β in paraffin-embedded lung tissue from 66 patients with NSCLC.The area and degree of stain were evaluated to determine the positive rate，which was compared between with or without metastasis of lymph nodes，different pathological types and TNM clinical stages.Results MIP-1β protein was found in cytoplasm of malignant cells of squama cell cancer and adenocarcinoma without significant difference between them，while not found in bronchus-alveolus cell cancer.The MIP-1β mRNA expression in squama cell cancer and adenocarcinoma were significant higher than which in bronchus-alveolus cell cancer without significant difference between each other.The positive rates of MIP-1β in lung cancer of Ⅰ，Ⅱ and Ⅲ stages were 74.2%，29.4% and 85.7% respectively，which of Ⅰ and Ⅲ stages cancer were significant higher than Ⅱ stage without significant difference between each other.The positive rates of MIP-1β in lung cancer with or without metastasis of lymph nodes were 45.8% and 76.3% respectively with significant difference between them.Conclusion MIP-1β is expressed in lung cancer cells and relates to the pathological type，TNM stage and the metastasis of lymph nodes.
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.
