Objective To study the effects of FTY720 pretreatment on ventilator-induced lung injury (VILI) in rats in order to explore the role of sphingosine-l-phosphate receptor 1 (S1PR1).Methods Forty healthy adult male SD rats weighing 300-350 g were randomly (randlom number) divided into 4 groups (n=10 each):group CV (conventional tidal volume VT =8 mL/kg),group HV (high tidal volume VT =40 mL/kg),group HF and group HFW.The rats in group HF received intra-gastric administration of FTY720 10 mg · kg-1 · d-1 for 7 days,while additional dose of W146 (S1PR1 antagonist) 1 mg · kg-1 · d-1 was administrated in group HFW before high tidal volume ventilation.After 4-hour mechanical ventilation,arterial blood samples were obtained for blood gas analysis before the animals were sacrificed.The lungs were harvested for histopathologic observation.Apoptosis rate in lung tissue was determined with flow cytometry.W/D lung weight ratio,pulmonary permeability index (PPI),total protein,and TNF-α,IL-1β in bronchoaveolar lavage fluid (BALF) were measured.All data were analyzed by oneway analysis of variance (ANOVA),The intergroup comparisons were analyzed by the least-significantdifference (LSD) test by using SPSS version 20.0 software.Differences were considered statistically significant if P ＜ 0.05.Results Compared with group CV,the level of PaO2 [(73.6 ± 8.9) vs.(50.5 ± 6.0)] was decreased,the levels of W/D [(3.12 ± 0.27) vs.(5.12 ± 0.56)],PPI [(0.08 ±0.03) vs.(0.30 ± 0.06)],apoptosis rate [(10.6 ±2.9) vs.(48.5±6.7)],total protein [(5.8 ±2.1) vs.(15.4±5.6)] and TNF-α [(24.3±5.7) vs.(108.4±16.0)] andIL-1β [(90.6±14.1) vs.(338.5 ± 44.3)] were increased in group HV (P ＜ 0.05).Compare with group HV,PaO2 [(50.5 ± 6.0) vs.(65.9±10.3)] was increased,W/D[(5.12±0.56)vs.(3.85±0.37)],PPI[(0.30± 0.06)vs.(0.14±0.03)],apoptosis rate [(48.5 ±6.7)vs.(25.6 ±5.3)],total protein [(15.4±5.6) vs.(8.9±2.5)],TNF-cα [(108.4±16.0) vs.(75.6±10.3)] andIL-1β [(338.5 ±44.3) vs.(188.9 ±33.8)] in BALF were decreased in group HF (P ＜0.05).PaO2 [(50.5±6.0) vs.(59.7±7.8)] was higher,W/D[(5.12±0.56) vs.(4.44±0.30)],PPI [(0.30±0.06)vs.(0.19±0.09)] andIL-1β[(338.5-±44.3) vs.(246.8±24.6)] levels were lower in group HFW than those in group HF There were no significant differences in apoptosis rate[(48.5±6.7)vs.(41.3±6.8)],totalprotein[(15.4±5.6)vs.(10.4±2.7)] and TNF-α level [(108.4 ± 16.0) vs.(97.5 ± 10.3)] between HFW group and HF group (P ＞ 0.05).Compare with group CV,The histopathologic damage of lung tissue was obvious in group HV and group HFW,it was attenuated by pretreatment with FTY720 in group HF.Conclusions FTTY720 pretreatment provides protective effects against ventilation-induced lung injury in rats,and S1PR1 may mediate the protection through reducing apoptosis rate and inflammatory reaction.

Objective To evaluate the role of cyclooxygenase-2 (COX-2) in ventilator-induced lung injury in rats.Methods Thirty healthy adult male Sprague-Dawley rats,aged 3.0-3.5 months,weighing 300-350 g,were randomly divided into 3 groups (n =10 each) using a random number table:traditional tidal volume group (group T,VT =8 ml/kg),large tidal volume group (group L,VT =40 ml/kg) and NS398 (selective COX-2 inhibitor,VT =40 ml/kg) group (group N).In group N,8 mg/kg NS398 (in 2 ml of 10％ dimethyl sulfoxide) was injected intraperitoneally at 1 h before ventilation,while dimethyl sulfoxide 2 ml was administrated instead of NS398 in T and L groups.After 4 h of mechanical ventilation,arterial blood samples were obtained for blood gas analysis and PaO2 was recorded.The animals were sacrificed and lungs removed for microscopic examination and for determination of wet/dry lung weight ratio (W/D ratio) and concentrations of total protein,intercellular adhesion molecule-1 (ICAM-1),tumor necrosis factor-alpha (TNF-α),NO and 6-keto-prostaglandin F1alpha (6-keto-PGF1 α) in bronchoaveolar lavage fluid (BALF).Pulmonary permeability index (PPI) and TXB2/6-keto-PGF1 α ratio were calculated.Results Compared with group T,PaO2 was significantly decreased,W/D ratio and PPI were increased,the total protein,ICAM-1,TNF-α and NO levels and TXB2/6-keto-PGF1 α ratio in BALF were increased in group L(P ＜ 0.05).PaO2 was significantly higher,W/D ratio and PPI were lower,and total protein,ICAM-1,TNF-α and NO levels and TXB2/6-keto-PGF1 α ratio in BALF were lower in group NS than in group L (P ＜ 0.05).The damage to lung tissues was severe in group L,and obviously alleviated in group N.Conclusion COX-2 is involved in ventilator-induced lung injury in rats.

0.05).At the T1,T3,T4,T7 time point,changes of the MAP and HR were more stable in TCI group than those in control group.The awakening time and extubation time in TCI group was obviously shorter in than that in control group.The OAAS scores after extubation were higher and the VRS scores 30 min after extubation were lower in TCI group than those in control group(P

Objective To investigate the effect of methylene blue (MB) on oxygen metabolism in patients with septic shock. MethodsForty ASA Ⅱ or Ⅲ patients with septic shock aged 38-64 yr weighing 48-75 kg undergoing emergency surgery were randomly divided into 2 groups ( n = 20 each): group Ⅰ norepinephrine (group NE) and group Ⅱ MB. The patients were unpremedicated. Anesthesia was induced with midazolam, etomidate,sufentanil and vecuronium and maintained with inhalation of 0.5％-1.5％ sevoflurane and intermittent iv boluses of sufentanil and vecuronium. The patients were mechanically ventilated after tracheal intubation. PETCO2 was maintained at 35-45 mm Hg. During operation MB was infused at 0.5-1.0 mg·kg-1·h-1 in group MB and NE at 0.5-2.0 μg· kg-1 · min-1 in group NE respectively to maintain hemodynamic stability. Radial artery was cannulated and connected with Vigileo cardiac output monitor. Right internal jugular vein was cannulated for CVP monitoring.HR, SvO2, MAP, CVP, SV and CI were continuously monitored. Arterial and central venous blood samples were collected simultaneously before induction of anesthesia (T0, baseline), immediately before (T1) and at 30, 60 and 90 min after skin incision (T2-4) and at the end of operation (T5) . Blood gas analysis was performed. O2 consumption index (VO2I), O2 delivery index (DO2I) and O2 extraction rate (ERO2) were calculated. Blood lactate concentration was measured. Results MAP, HR, CVP, SVRI, DO2I, VO2I and ERO2 were significantly higher,while CI and blood lactate concentration lower during operation (T2-5) in group MB than in group NE. MAP, HR,CVP, SVRI, VO2I, DO2I, and ERO2 were significantly higher, while CI and blood lactate concentration were lower during operation (T2-5) as compared with the baseline values at T0 in group MB. In group NE there were no significant change in MAP, HR, CVP and DO2I during operation (T2-5 ) as compared with the baseline at T0. ConclusionIntravenous infusion of MB at 0.5-1.0 mg·kg-1·h-1 during operation may improve hemodynamics and oxygen metabolism in patients with septic shock.

AIM:To investigate isometric force displacement in isolated rat main pulmonary artery rings and right main branch pulmonary artery(second pulmonary artery)rings during hypoxia hypercapnia and the role of mitogen activated protein kinase(MAPK).METHODS:The main pulmonary artery rings were dissected from the male Sprague-Dawley rats and were randomly divided into control group and hypoxia hypercapnia group.The second pulmonary artery rings were also randomly divided into control group,hypoxia hypercapnia group,DMSO incubation group,U0126 incubation group and SB203580 incubation group.The tension changes of pulmonary artery rings were monitored in vitro.RESULTS:Under normoxia conditions,there was no statistically significant change between main pulmonary artery rings and second pulmonary artery rings.A biphasic pulmonary artery contractile response to hypoxia hypercapnia in the second pulmonary artery rings was observed instead of a sharp and transient increase in the main pulmonary artery tension.Both p38 MAPK inhibitor SB203580 and ERK1/2 inhibitor U0126 significantly attenuated the delayed,but not early,contractile phase of the biphasic pulmonary artery contraction.CONCLUSION:Acute hypoxia hypercapnia causes a biphasic pulmonary artery contractile response in the second pulmonary artery,and p38 MAPK and ERK1/2 may be two key mediators in the process.

Objective To check the changes of endothelial progenitor cell (EPC) number of patients with anaplastic large cell lymphoma (ALCL) in the peripheral blood,investigate their clinical significance.Methods The number of EPC in blood was determined by FCM method in 30 patients with ALCL and 10 healthy cases as the control group.Results The number of EPC in the peripheral blood of patients with ALCL before treatment was significantly higher (15.530±28.659/μl) than that in control group (0.515 ±0.294/μl,P ＜ 0.001).The number of EPC of ALCL patients in the high-risk groups (21.521±36.057/μl) and the middle-risk groups (16.830±24.273/μ1) differently increaasd than that of the low-risk group (6.508±7.356/μl,P ＜ 0.01),but between the high-risk groups and the middle-risk groups there was no significant value (P ＞ 0.05).There were significant difference between the number of EPC of ALK+-ALCL (8.367±9.609/μl) and ALK-ALCL (22.541± 20.845/μl) patients (P ＜ 0.01).The survive curve before 60 weeks had significant difference between groups of ＞20/μl and ＜20/μl of EPC.Conclusion EPC may be correlated with progression of the disease in a certain degree.Dynamic observation with the level of EPC may be used to evaluate the treatment outcomes and act as a prognostic marker for ALCL.

Objective To evaluate the impact of the re-modified Sugiura procedure on portal hemodynamics and liver function in cirrhotic patients with portal hypertension.Methods Forty patients with cirrhosis and portal hypertension who underwent the re-modified Sugiura procedure in the Yichang Second People's Hospital from June 2006 to October 2014 were studied.Changes in the free portal pressure (FPP),portal venous flow (PVF) and liver functions before and after operation were analyzed.Results (1) The FPP at different phases of the operation (after opening the abdomen,after splenectomy,and after devascularization) were (43.2 ± 1.8) cmH2O,(34.8 ± 1.6) cmH2O and (35.2 ± 1.7) cmH2O,respectively.There were significant differences in FPP between the phases of after splenectomy and after opening the abdomen,as well as after devascularization and after opening the abdomen (P ＜ 0.05).There was no significant difference in FPP between after devascularization and after splenectomy (P ＞ O.05).(2) The PVF,which were measured with Doppler sonography at 4 time points (preoperative 1 day,postoperative 10 days,postoperative 6 months,postoperative 18 months),were (1 420.4 ± 137.7) ml/min,(1 205.2 ± 126.7) ml/min,(875.8 ± 118.0) ml/min and (893.8 ± 114.7) n1/min,respectively.There were significant differences in PVF between postoperative 10 days and preoperative 1 day,between postoperative 6 months and postoperative 10 days,as well as between postoperative 18 months and preoperative 1 day (P ＜0.05).There was no significant difference in PVF between postoperative 18 months and postoperative 6 months (P ＞0.05).(3)The liver functions were evaluated using the Child-Pugh score at 4 time points (preoperative 1 day,postoperative 10 days,postoperative 6 months,postoperative 18 months).There were no significant differences among the time points,(P ＞ 0.05).Conclusion The re-modified Sugiura's procedure durably,appropriately and effectively reduced the PVF and FPP,but it did not have any negative effects on the liver functions of patients with cirrhosis.

OBJECTIVETo investigate the effect of Shenmai injection on vascular endothelial active facters nitric oxide (NO) and endothelin-1 (ET-1), and pulmonary gas exchange induced by tourniquet deflation in patients undergoing lower extremity surgery.

METHODTwenty-six patients scheduled for unilateral lower extremity surgery were randomly divided into 2 groups: control group (group C, n = 14) and Shenmai injection group (group SM, n = 12). All the patients agreed to a combined spinal-epidural anesthesia at the L2-L3 interspace and a radial artery catheter was placed for sampling. Patients in group SM were injected Shenmai injection 0.6 mL x kg(-1) and physiological saline 100 mL, while patients in group C were injected equal volume of normal saline instead 15 min before tourniquet inflation. Blood samples which were used for blood gas analysis and measurement of nitric oxide (NO) and endothelin-1 (ET-1) were taken before tourniquet inflation (T0, baseline) and 30 min (T1), 2 h (T2), 6 h (T3), 24 h (T4) after tourniquet deflation.

RESULTCompared with the baseline values at T0, in group C at T3 P(a) O2 and the levels of NO were significantly decreased, while P(A-a) DO2 and the levels of ET-1 at T3 were significantly increased (P < 0.05 or P < 0.01), in group SM, the levels of NO at T3 were significantly decreased (P < 0.05). Compared with group C, the changes of P(a)O2, P(A-a) DO2, NO and ET-1 were significantly mitigated in group SM.

CONCLUSIONThe concentrations of NO and ET-1 is connected with the pulmonary gas exchange impairment induced by tourniquet application. Shenmai injection can improve the pulmonary gas exchange based on rising the level of NO, reducing the level of ET-1.

Adult ; Drug Combinations ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; Endothelin-1 ; blood ; metabolism ; Endothelium, Vascular ; drug effects ; metabolism ; physiopathology ; Female ; Humans ; Injections, Intravenous ; Male ; Middle Aged ; Nitric Oxide ; blood ; metabolism ; Pulmonary Gas Exchange ; drug effects ; Tourniquets ; adverse effects