Effects of lipoxin A4 on human type Ⅱ alveolar epithelial cell wound repair, proliferation and apoptosis / 中华麻醉学杂志

Objective To evaluate the effects of lipoxin A4 (LXA4) on human type Ⅱ alveolar epithelial cell wound repair,proliferation and apoptosis.Methods Experiment Ⅰ Human type Ⅱ alveolar epithelial cells were inoculated in 24-well plates and divided into 4 groups (n=10 each) using a random number table:control group (group C),1 nmol/L LXA4 group (group L1),10 nmol/L LXA4 group (group L2) and 100 nmol/L LXA4 group (group L3).Cells were cultured in normal culture atmosphere in group C.Cells were incubated with 1,10 and 100 nmol/L LXA4 in L1,L2 and L3 groups,respectively.The scratch wound assay was performed at 36 h of culture or incubation.Cell proliferation was measured at 24 h of culture or incubation.Experiment Ⅱ Human type Ⅱ alveolar epithelial cells were inoculated in 96-well plates and divided into 5 groups using a random number table:control group (group C,n=10),Fas-ligand group (n =10),Fas-ligand+LXA4 group (n =10),Fas-ligand+TNF-α group (n =5) and Fas-ligand+TNF-α+LXA4 group (n=5).Cells were incubated with 100 ng/ml Fas-Ligand,100 ng/ml Fas-Ligand plus 100 nmol/L LXA4,100 ng/ml Fas-Ligand plus 100 ng/ml TNF-α,and 100 ng/ml Fas-Ligand plus 100 ng/ml TNF-α plus 100 nmol/L LXA4 in Fas-ligand,Fas-ligand+LXA4,Fas-ligand+TNF-α,and Fas-ligand +TNF-α+LXA4 groups,respectively.The cell viability was measured at 24 h of culture or incubation.Cell apoptosis was detected using the flow cytometry,and apoptosis rate was calculated in C,Fas-ligand and Fas-ligand+LXA4 groups.Results Experiment Ⅰ Compared with group C,the percentage of cell repair size and percentage of proliferation were significantly increased in L1,L2 and L3 groups (P＜0.05 or 0.01).Compared with group L1,the percentage of cell repair size and percentage of proliferation were significantly increased in group L3 (P＜ 0.01),and no significant change was found in the parameters mentioned above in group L2 (P＞0.05).Experiment Ⅱ Compared with group C,the cell viability was significantly decreased,and the apoptosis rate was increased in group Fas-ligand,the cell viability was significantly decreased in group Fas-ligand+TNF-α (P＜ 0.01),and no significant change was found in the cell viability or apoptosis rate in group Fas-ligand+LXA4 or in the cell viability in group Fas-ligand+TNF-α+LXA4 (P＞0.05).Compared with group Fas-ligand,the cell viability was significantly increased,and the apoptosis rate was decreased in group Fas-ligand+LXA4 (P＜ 0.05).The cell viability was significantly higher in group Fas-ligand +TNF-α + LXA4 than in group Fas-ligand +TNF-α (P ＜ 0.01).Conclusion LXA4 can promote human type Ⅱ alveolar epithelial cell wound repair and proliferation and inhibit the apoptosis.

LipoxinA4 reduces lipopolysaccharide-induced expression of cyclooxygenase-2 and prostaglandin E2 in primary lung fibroblasts of rat / 中华急诊医学杂志

Objective To explore the effects of lipoxinA4 on expression of cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in rat primary lung fibroblast cells (LF) after lipopolysaccharide (LPS) challenge.Methods Primary lung fibroblast cells were incubated with various concentrations (0.1,1,10 μg/mL) of LPS for different lengths of time (3,6,9 h).Then primary lung fibroblast cells were still incubated in DMEM medium containing LPS in the presence or absence of lipoxinA4.After incubation,the supematant of medium was collected and the level of PGE2 was detected by using ELISA.The cells were harvested,and COX-2 protein was analyzed by Western blot.Results The model of acute inflammation in fibroblasts was well established by administering 1 μg/mL LPS in fibroblasts for 6 hours.Induction of COX-2 protein by LPS was inhibited by lipoxinA4.The levels of PGE2 in control group,LPS group and LPS + LipoxinA4 group were 55.84 pg/mL,411.73 pg/mL and 307.07 pg/mL,respectively,and there was a significantdifference between LPS group and LPS + LipoxinA4 group (P ＜0.01).Conclusion LipoxinA4 down-regulates the expression of the COX-2 induced by LPS in primary lung fibroblast cells and consequently inhibits the production of PGE2 in a dose dependent manner.

Clinical relevance of angiographic coronary collaterals during primary coronary intervention for acute ST-elevation myocardial infarction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Collaterals to occluded infarct-related coronary arteries (IRA) have been observed after the onset of acute ST-elevation myocardial infarction (STEMI). We sought to investigate the impact of early coronary collateralization, as evidenced by angiography, on myocardial reperfusion and outcomes after primary percutaneous coronary intervention (PCI).</p><p><b>METHODS</b>Acute procedural results, ST-segment resolution (STR), enzymatic infarct size, echocardiographic left ventricular function, and major adverse cardiac events (MACE) at 6-month follow-up were assessed in 389 patients with STEMI undergoing primary PCI for occluded IRA (TIMI flow grade 0 or 1) within 12 hours of symptom-onset. Angiographic coronary collateralization to the occluded IRA at first contrast injection was graded according to the Rentrop scoring system.</p><p><b>RESULTS</b>Low (Rentrop score of 0 or 1) and high (Rentrop score of 2 or 3) coronary collateralization was detected in 329 and 60 patients, respectively. Patients with high collateralization more commonly had prior stable angina and right coronary artery occlusion, but less often had left anterior descending artery occlusion. At baseline, these patients presented with less extent of ST-segment elevation and lower serum levels of creatine kinase myocardial band (CK-MB) and cardiac troponin I (cTnI). Procedural success rate, STR, corrected TIMI flame count, and area under the curve of CK-MB and cTnI measurements after the procedure were similar between patients with high collateralization and those with low collateralization (for all comparisons P > 0.05). There were no differences in left ventricular ejection fraction and rates of MACE at 6 months according to baseline angiographic collaterals to occluded IRA.</p><p><b>CONCLUSIONS</b>In patients with acute STEMI undergoing primary PCI within 12 hours of symptom-onset, coronary collateralization to the occluded IRA was influenced by clinical and angiographic features. Early recruitment of collaterals limits infarct size at baseline, but has no significant impact on myocardial reperfusion after the procedure and subsequent left ventricular function and clinical outcomes.</p>

The influence of diabetes on left ventricular remodeling after primary percutaneous coronary intervention for patients with acute myocardial infarction / 中国介入心脏病学杂志

Objective To investigate the influence of diabetes mellitus (DM) on left ventricular(LV) remodeling in patients with acute ST-segment elevation myocardial infarction (STEMI) treated by primary percutaneous coronary intervention (PCI) within 12 hours of symptom onset. Methods Four hundred and fifty-one consecutive patients with acute STEMI treated by primary PCI were prospectively enrolled in the current study. Baseline, angiographic and PCI features and prevalence of LV remodeling at one-week during hospitalization and 6-month clinical follow-up by two-dimensional echocardiography were compared between 93 diabetic and 358 non-diabetic patients. Results Despite similar baseline clinical and angiographic characteristics, symptom-to-door time was longer (399±106 min vs. 321±116 min, P=0.006) and prevalence of multivessel disease was higher (65.6%vs. 51.7%, P=0.02) in diabetic patients. More patients in diabetic group had LV remodeling at 6-month clinical follow-up (29.0%vs. 17.3%, P=0.01), and DM was an independent predictor of LV remodeling (RR 2.1, 95%CI 1.31-4.79, P=0.02). The rate of rehospitalization due to heart failure did not differ between diabetic and non-diabetic patients (12.9%vs. 8.1%, P=0.15), however, more adverse events occurred in patients with LV remodeling comparing to those without LV remodeling (25.8% vs. 6.6%, P < 0.001). Conclusions Diabetic patients with STEMI often have an increased risk of LV remodeling after treated by primary PCI. Thus, comprehensive therapeutic strategy for diabetic patients presented with STEMI is required considering the poor prognosis of these patients with LV remodeling.

Efficacy and safety of intra-coronary bolus injection of tirofiban during primary percutaneous coronary intervention for patients with acute ST-segment elevation myocardial infarction / 中国介入心脏病学杂志

Objective To analyse and compare the effects and safety of early use (in emergency room, intravenous loading followed by infusion) with bolus injection during primary PCI of tirofiban, on post-procedural TIMI flow and 30d clinical outcomes. Methods Seven hundred and seven patients with acute STEMI treated by primary PCI in Ruijin hospital were retrospectively and enrolled screened. Among them, 86 patients with single bolus intra-coronary injection of tirofiban (25 μg/kg) during the procedure were served as observation group. Baseline, angiographic, PCI features and rate of major adverse cardiac events (MACE) at 30 d follow-up were compared with those received early intravenous infusion of tirofiban (10ug/kg bolus followed by 0.15μg/(kg·min) intravenous infusion)(control group, n=239). Results Compared with control group, patients in observation group were older[(63.8±11.4) vs. (57.9±8.8), P=0.01], had higher prevalence of hypertension (58.6%vs. 51.0%, P=0.005), multivessel disease (57.0%vs. 34.3%, P<0.001), and female in gender (40.7%vs. 25.1%, P=0.006). Post-procedural TIMI flow in culprit vessel and TMP grade were comparable between the two groups (P=0.66 and P=0.48, respectively). Reduction in TIMI minimal bleeding events were found in the observation group (2.3%vs. 9.6%, P=0.03). MACE free survival rate at 30d clinical follow-up was similar between the two groups (P=0.48). Conclusions Single bolus intra-coronary injection of tirofiban exerts similar effects in post-procedural TIMI flow, TMP grade in culprit vessel and 30d clinical outcomes compared with early use in emergency room with intra-venous loading and infusion, nevertheless, intra-coronary injection resulted in significantly reduced TIMI minimal bleeding events. Prospective, randomized clinical study is mandatory to prove our current results.

Differentiation of GDNF and NT-3 dual gene-modified rat bone marrow mesenchymal stem cells into enteric neuron-like cells / 华中科技大学学报（医学）（英德文版）

Bone marrow mesenchymal stem cells (BMSCs) have been shown to be multipotent cells that possess high self-replicating capacity. The purpose of our study was to investigate the feasibility of using enteric neuron-like cells obtained by in vitro induction and differentiated from rat BMSCs for the treatment of Hirschsprung's disease (HD). Glial cell-derived neurotrophic factor (GDNF) and neurotrophin-3 (NT-3) are neurotrophic factors that play important roles in neuronal development, differentiation, survival and function. Meanwhile, GDNF mutations are a major cause of HD. In this study, BMSCs were transfected with eukaryotic expression plasmids co-expressing GDNF and NT-3, and the transfected cells displayed neuron-like changes after differentiation induced by fetal gut culture medium (FGCM). Immunofluorescence assay showed positive expression of the neuronal marker NSE and the enteric neuronal markers PGP9.5, VIP and nNOS. Reverse transcription-polymerase chain reaction (RT-PCR) revealed the expression of GDNF and NT-3 in transfected BMSCs. The present study indicates that genetically modified BMSCs co-expressing GDNF and NT-3 are able to differentiate into enteric neuronal cells and express enteric nerve markers when induced by FGCM. This study provides an experimental basis for gene therapy to treat enteric nervous system-related disorders, such as HD.

Effect of methylene blue on oxygen metabolism in patients with septic shock / 中华麻醉学杂志

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.