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Objective To investigate the inhibitory effect and mechanism of soybean-derived Bowman-Birk inhibi-tor (BBI)on LPS-induced expression of inflammatory cytokines in intestinal epithelial cells.Methods Cytotoxicity effect of LPS and BBI on intestinal epithelial cells was analyzed by MTT assay.Intestinal epithelial cells were pre-treated with BBI,followed by LPS stimulation,expression of inflammatory cytokines(TNF-α,IL-1β,IL-8,and MCP-1)was detected by quantitative real-time polymerase chain reaction;the activation of NF-κB was measured by pNF-κB-luc system and Western Blot.Results The maximum concentration of LPS (10000 ng/mL)and BBI (1000 μg/mL)had no cytotoxicity effect on intestinal epithelial cells.LPS could potently up-regulate the expression of inflammatory cytokines(TNF-α,IL-1β,IL-8,and MCP-1 ),the up-regulation was positively correlated to the concentration of LPS;LPS-induced expression of inflammatory cytokines in intestinal epithelial cells could achieve the highest level,then decreased over time.The up-regulation of LPS on inflammatory cytokines in intestinal epi-thelial cells had dose-time effect;when intestinal epithelial cells were pretreated by BBI for 6 hours,the inhibitory effect of BBI on LPS-induced expression of inflammatory cytokines in intestinal epithelial cells was most obvious, and had dose-time effect.Conclusion BBI can potently inhibit LPS-induced expression of inflammatory cytokines through inhibiting NF-κB in intestinal epithelial cells.
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Objective To explore the ef fi cacy and safety of long-term use of low dose glucocorticoids in acute respiratory distress syndrome (ARDS). Methods Fifty ARDS patients were randomly divided into two groups. The control group(25 patients)received non-invasive or invasive mechanical ventilation,antibiotics and support treatments. The glucocorticoids group(25 patients)received the same treatments plus long-term use of low dose glucocorticoids. Results The mortality in glucocorticoids group(32％(8/25))was much lower than that in the control group(60％(15/25))(P < 0.05). The ventilator-free days and organ failure-free days within 28d in glucocorticoids group were significantly higher than those in the control group (P < 0.05). The oxygenation index and the serum IL-8 levels in glucocorticoids group at 14d and 28d were higher than those in the control group(P<0.05). Compared to the control group ,long-term use of low dose glucocorticoids in ARDS did not increase fasting blood-glucose at 7d,gastrointestinal bleeding and hospital infections within 28d. Conclusions Long-term use of low dose glucocorticoids in ARDS could reduce the serum IL-8 levels and improve the prognosis.
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Objective To investigate the inhibitory effect and mechanism of soybean-derived Bowman-Birk inhibi-tor (BBI)on LPS-induced expression of inflammatory cytokines in intestinal epithelial cells.Methods Cytotoxicity effect of LPS and BBI on intestinal epithelial cells was analyzed by MTT assay.Intestinal epithelial cells were pre-treated with BBI,followed by LPS stimulation,expression of inflammatory cytokines(TNF-α,IL-1β,IL-8,and MCP-1)was detected by quantitative real-time polymerase chain reaction;the activation of NF-κB was measured by pNF-κB-luc system and Western Blot.Results The maximum concentration of LPS (10000 ng/mL)and BBI (1000 μg/mL)had no cytotoxicity effect on intestinal epithelial cells.LPS could potently up-regulate the expression of inflammatory cytokines(TNF-α,IL-1β,IL-8,and MCP-1 ),the up-regulation was positively correlated to the concentration of LPS;LPS-induced expression of inflammatory cytokines in intestinal epithelial cells could achieve the highest level,then decreased over time.The up-regulation of LPS on inflammatory cytokines in intestinal epi-thelial cells had dose-time effect;when intestinal epithelial cells were pretreated by BBI for 6 hours,the inhibitory effect of BBI on LPS-induced expression of inflammatory cytokines in intestinal epithelial cells was most obvious, and had dose-time effect.Conclusion BBI can potently inhibit LPS-induced expression of inflammatory cytokines through inhibiting NF-κB in intestinal epithelial cells.
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Objective To explore the ef fi cacy and safety of long-term use of low dose glucocorticoids in acute respiratory distress syndrome (ARDS). Methods Fifty ARDS patients were randomly divided into two groups. The control group(25 patients)received non-invasive or invasive mechanical ventilation,antibiotics and support treatments. The glucocorticoids group(25 patients)received the same treatments plus long-term use of low dose glucocorticoids. Results The mortality in glucocorticoids group(32％(8/25))was much lower than that in the control group(60％(15/25))(P < 0.05). The ventilator-free days and organ failure-free days within 28d in glucocorticoids group were significantly higher than those in the control group (P < 0.05). The oxygenation index and the serum IL-8 levels in glucocorticoids group at 14d and 28d were higher than those in the control group(P<0.05). Compared to the control group ,long-term use of low dose glucocorticoids in ARDS did not increase fasting blood-glucose at 7d,gastrointestinal bleeding and hospital infections within 28d. Conclusions Long-term use of low dose glucocorticoids in ARDS could reduce the serum IL-8 levels and improve the prognosis.
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Objective To study the effects of long-term use of simvastatin on mechanical ventilation induced lung injury.Methods Forty SPF adult male Sprague-Dawley (SD) rats weighing 300-350 g were randomly divided into four groups (n =10,each):normal saline (NS) control group (group A),mechanical ventilation group (group B),simvastatin control group (group C),and simvastatin + mechanical ventilation group (group D).The rats in groups C and D were treated with simvastatin dissolved in 1 mL NS by gavage with a dose of 10 mg/kg,and the rats in groups A and B were treated with the same volume of NS by gavage for 28 days.Half an hour after the last garage,the rats in groups B and D underwent tracheostomy and intubation for 4 hours,and then received a tidal volume of 30 mL/kg with the respiratory frequency of 40 times/min,inspiratory:expiratory ratio of 1:3,and the rats in groups A and C received tracheostomy and intubation,spontaneous breathing for 4 hours.Four hours later rats were sacrificed by abdominal aorta bloodletting,and the lung tissue was harvested for hematoxylin and eosin (HE) staining to observe pathological changes under light microscope.The activity of malondialdehyde (MDA),superoxide dismutase (SOD),and myeloperoxidase (MPO) was determined.The lung wet/dry weight ratio (W/D) and white blood cell (WBC) count in bronchoalveolar lavage fluid (BALF) were determined.The levels of interleukins-6 (IL-6) and tumor necrosis factor-α (TNF-α) in BALF were determined by enzyme linked immunosorbent assay (ELISA).Results Under light microscope,the structure of lung tissue was integrity in groups A and C without obvious edema and inflammatory cells aggregation;the pathological changes in lung tissue in group B was obvious;and the alveolar structure was clear in group D,pulmonary edema and inflammatory cells aggregation were significantly reduced as compared with those of group B.Compared with group A,SOD activity in group B was significantly decreased (U/g:17.97±2.27 vs.28.51 ±4.58,P ＜ 0.01),while MDA,MPO,lung W/D ratio and WBC,IL-6,TNF-α in BALF were significantly increased [MDA (μmol/g):5.40 ± 0.71 vs.3.56 ± 0.55,MPO (U/g):1.26±0.29 vs.0.68±0.12,lung W/D ratio:6.60±0.99 vs.4.84±0.26,WBC (× 109/L):6.59±0.82 vs.2.35±1.31,IL-6 (ng/L):207.11± 18.67 vs.123.17±20.15,TNF-o (ng/L):421.38±36.27 vs.207.15±44.39,all P ＜ 0.01].Compared with group B,SOD activity in group D was significantly increased (U/g:22.05±2.45 vs.17.97±2.27,P ＜ 0.05),MDA,MPO,lung W/D ratio,and WBC,IL-6,TNF-α in BALF were significantly decreased [MDA (μmol/g):3.77±0.55 vs.5.40±0.71,MPO (U/g):0.96±0.14 vs.1.26±0.29,lung W/D ratio:5.16±0.42 vs.6.60±0.99,WBC (× 109/L):3.18± 1.24 vs.6.59±0.82,IL-6 (ng/L):147.90±21.70 vs.207.11 ± 18.67,TNF-α (ng/L):237.16±50.83vs.421.38 ± 36.27,all P ＜ 0.01].There were no significant difference in all parameters between group C and group A.Conclusion The long-term simvastatin treatment could significantly reduce lung injury induced by mechanical ventilation in rats,and its mechanism was related with simvastatin reduced oxidation-antioxidant imbalance and the inflammatory cytokines activity changes.
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Objective To investigate the differences in dosimetry between conformal radiotherapy (CRT),field-in-field intensity-modulated radiotherapy (FIF-IMRT),and intensity-modulated radiotherapy (IMRT) after breast-conserving surgery for left-sided breast cancer.Methods A total of 31 patients who underwent breast-conserving surgery for left-sided breast cancer were randomly selected,and the plans for CRT,FIF-IMRT,and IMRT were developed.The dose-volume histogram (DVH) was used for self-control study,and the non-parametric test was used to compare the differences in target volume and doses to organs at risk (OARs).Results All the three methods met the requirements of the prescribed doses.The CRT group had a higher V105 of the target volume and higher heart V30 and Dmax (P=0.000,0.000,0.000).The IMRT group had higher V5 and Dmean (P=0.000,0.000),as well as a higher lung V5 and a lower lung V40 (P=0.000,0.000).The FIF-IMRT group had the lowest Dmean (P=0.000),and the IMRT group had significantly higher Dmean and Dmax of the right lung and the spinal cord than the other two groups (P=0.000,0.000,0.000,0.000).The FIF-IMRT group had a significantly lower single hop count than the other two groups (P=0.000).Conclusions CRT has a good dose distribution in the target volume,but greatly injures the surrounding tissues.FIF-IMRT can well protect OARs and cause less damage to the device.
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Objective To evaluate the effect of long-term use of simvastatin on aquaporin 5 (AQP5) expression in a rat model of ventilator-induced lung injury.Methods Thirty-two adult male Sprague-Dawley rats, weighing 250-280 g, were randomly divided into 4 groups (n=8 each) using a random number table: control group (group C), simvastatin group (group Sim), mechanical ventilation group (group MV) and simvastatin + mechanical ventilation group (group SMV).In C and Sim groups, normal saline 1 ml/d and simvastatin 10 mg · kg-1 · d-1 were injected, respectively, through a gastric tube into stomach for 4 weeks, and then the rats were tracheostomized, and mechanically ventilated, and the animals kept spontaneous breathing for 4 h.In MV and SMV groups, normal saline 1 ml/d and simvastatin 10 mg · kg-1 · d-1were injected, respectively, through a gastric tube into stomach for 4 weeks, and then the rats were tracheostomized, and mechanically ventilated (tidal volume 50 ml/kg) for 4 h.The rats were then sacrificed, and lungs were removed for determination of wet to dry lung weight ratio (W/D ratio), activities of myeloperoxidase (MPO) and superoxide dismutase (SOD), malondialdehyde (MDA) content,and expression of AQP5 protein and mRNA in lung tissues, and for microscopic examination of pathological changes.Results Compared with group C, the W/D ratio, MPO activity, and MDA content were significantly increased, the SOD activity was decreased, and the expression of AQP5 protein and mRNA was down-regulated in group MV (P＜0.01).Compared with group MV, the W/D ratio, MPO activity, and MDA content were significantly decreased, the SOD activity was increased, and the expression of AQP5 protein and mRNA was up-regulated in group SMV (P＜0.01).The pathological changes of lungs were significantly mitigated in group SMV as compared with group MV.Conclusion Long-term use of simvastatin alleviates ventilator-induced lung injury, and the mechanism is related to down-regulated expression of AQP5 in rats.