Objectives To explore ventilation induced cytokine production and the role of oxidant stress in lung stretch. Methods Both in vitro and in vivo models of ventilator-induced lung injury (VILI) were used. Alveolar epithelial cells were stretched in vitro to mimic the lung injury in VILI. Rats were ventilated at large tidal volume to produce ventilator-induced lung injury in vivo. A total of 23 inflammatory cytokines were screened with micro gene array in stretched alveolar epithelial cells. Cytokines found to have up-regulated in cells were measured in serum and lung tissue of rats exposed to large tidal volume ventilation. For investigating the intracellular pathway of cytokine up-regulation in VILI, exogenous TNF-α or H2O2 was added to culture media of alveolar epithelial cells. Cytokines were then measured. To explore the role of oxidant stress in VILI, N-acetylcysteine (NAC), as an anti-oxidant, was used in vitro and in vivo. Results We found that transforming growth factor-β1 (TGF-β1 and transforming growth factor-β2 (TGF β2) were up-regulated in stretched alveolar epithelial cells and also in serum of rats with large tidal volume ventilation. Tumor necrosis factor-α (TNF-α) had no effects on TGF-β production in alveolar epithelial cells. Exogenous H2O2, as an oxidant, increased TGF-β production in alveolar epithelial cells. NAC, an anti-oxidant, decreased stretch induced TGF-β production, along with a down-regulation of oxidant injury. NAC also blocked the up-regulation of TGF-β in in vivo model of VILI. Conclusion TGF-β1 and TGF-β2 were up-regulated in VILI. Oxidant injury mediated up-regulation of TGF-β in VILI. NAC, which attenuated oxidant injury and blocked TGF-β up-regulation in VILI, could be a future therapeutic strategy in VILI.

Objective To investigate the related factors of serum carnitine deficiency in critical ill patients, and the influence of its deficiency on the length of hospital stay. Methods A prospective study was conducted. Critical ill patients with acute physiology and chronic health evaluationⅡ(APACHEⅡ)score>12 admitted to Department of Critical Care Medicine of the First Affiliated Hospital of Sun Yat-sen University from March 2013 to September 2013 were enrolled. Serum carnitine concentration and indexes of organ function were determined,and the tolerance of enteral nutrition within 5 days,the length of hospital stay,the length of intensive care unit(ICU)stay,and the hospital mortality were recorded. The relationship between serum carnitine and indexes mentioned above was analyzed. Results Thirty critically ill patients were enrolled. Serum carnitine concentration was very low in all critically ill patients,i.e. (8.92±5.05)μmol/L(normal reference value at 43.5 μmol/L)at hospital admission. Serum carnitine concentration in patients with APACHEⅡscore>23(7 cases)was significantly lower than that in those with APACHEⅡscore 12-23(23 cases,μmol/L:5.33±1.72 vs. 10.02±5.24,t=2.300,P=0.001). Serum carnitine concentration in patients with serum total bilirubin(TBil)>19μmol/L(9 cases)was significantly lower than that in those with TBil≤19μmol/L(21 cases,μmol/L:5.54±2.70 vs. 9.84±5.08,t=2.750,P=0.014). Serum carnitine concentration was negatively correlated with the APACHEⅡscore and the TBil(r=-0.387,P=0.035;r=-0.346,P=0.048). During the 5-day observation period,enteral feeding amount〔(5 134±1 173)mL〕was positively correlated with serum carnitine concentration(r=0.430,P=0.022). In 30 critical patients,the incidence of abdominal distension was 40.0%(12/30),and the serum carnitine concentration of patients with abdominal distension was lower compared with that of patients without abdominal distension(μmol/L:7.83±4.98 vs. 9.12±5.35,t=0.707,P=0.383). The incidence of diarrhea was 26.7%(8/30),and the serum carnitine concentration of diarrhea patients was lower compared with that of patients without diarrhea(μmol/L:8.27±5.78 vs. 9.73±4.78,t=0.607,P=0.576). The mean length of hospital stay was(34.72±16.66)days. The serum carnitine concentrations in patients with hospital stay≥45 days (8 cases)were lower compared with those in those<45 days(22 cases,μmol/L:5.71±3.23 vs. 9.95±5.26,t=1.627,P=0.020). No correlation was found between serum carnitine concentrations and the hospital stay(r=-0.165, P=0.385). The length of ICU stay was(18.60±10.72)days. Serum carnitine concentration in patients with the length of ICU stay>7 days(27 cases)was slightly lower than that in those with the length of ICU stay≤7 days (3 cases,μmol/L:8.44±5.00 vs. 13.24±3.65,t=1.610,P=0.119). No correlation was found between serum carnitine concentrations and the length of ICU stay(r=-0.019,P= 0.293). In-hospital mortality was 26.67%(8/30). No significant difference in serum carnitine concentrations was found between the death group and the survival group(μmol/L:12.24±6.52 vs. 7.72±3.91,t=-1.846,P=0.098). No correlation was found between serum carnitine concentrations and in-hospital mortality(r=0.340,P=0.066). Conclusions Carnitine deficiency is significant in critically ill patients,and it is correlated with disease severity and serum TBil. The total amount of lenteral feeding was lower,and hospital stay was prolonged in critically ill patients with low serum carnitine level.

AIM: To investigate the effect of ulinastatin plus thymosin - a, therapy on improving immune function in septic patients. METHODS: 70 patients were divided into two groups. One group was classical treatment group ( CT) with regular therapy and another group was classical treatment plus immunotherapy group ( CIT) with ulinastatin plus thymosin -a, for a week. The immune index before and after treatment on day 0,1,3 and 7 was observed, including the clinical and survival data. RESULTS: The most common pathogen of sepsis was bacteria, and infection by fungi was in rare. The common locations of bacteria observed were sputum and abdominal drainage. The level of TNF - α was significant lower in CIT group than that in CT group (P <0.05). IL - 10 level was significantly higher in CIT group than that in CT group (P < 0.05 ). IgG level was significant lower in CIT group than that in CT group (P < 0.05 ). No significant difference in the levels of IgA, IgM, C_3 and C_4 between two groups was observed (P > 0.05 ). CD4~+ T lymphocytes were significant higher in CIT group than those in CT group (P < 0.05 ). From day 7 to day 28, the lymphocytes and level of HLA -DR in CD14~+ monocytes were significant higher in CIT group than those in CT group (P < 0.05). The time of mechanical ventilation and vasopressors used in CIT group was shorter than those in CT group ( P < 0.05 ). But the length of stay and the cost in ICU showed no significant increase between these two groups (P >0.05). During hospitalization, 20 patients died in the CT group and 13 patients died in CIT group ( P < 0.05 ). The long - term survival time in CIT group was longer than that in CT group ( P < 0.05 ). CONCLUSION: Immunotherapy in septic patients can decrease TNF - α level and increase IL - 10 level. Immunotherapy in septic patients can increase IgC level slightly, CD4~+ T lymphocyte, and HLA - DR in CD14~+ monocytes, which improve the immune paralysis in septic patients. Immunotherapy can shorten the time of mechanical ventilation and vasopressors used, but it doesn't increase the length of stay and the cost.

Objectives To explore ventilation induced cytokine production and the role of oxidant stress in lung stretch. Methods Both in vitro and in vivo models of ventilator-induced lung injury (VILI) were used. Alveolar epithelial cells were stretched in vitro to mimic the lung injury in VILI. Rats were ventilated at large tidal volume to produce ventilator-induced lung injury in vivo. A total of 23 inflammatory cytokines were screened with micro gene array in stretched alveolar epithelial cells. Cytokines found to have up-regulated in cells were measured in serum and lung tissue of rats exposed to large tidal volume ventilation. For investigating the intracellular pathway of cytokine up-regulation in VILI, exogenous TNF-? or H_ 2O_ 2 was added to culture media of alveolar epithelial cells. Cytokines were then measured. To explore the role of oxidant stress in VILI, N-acetylcysteine (NAC), as an anti-oxidant, was used in vitro and in vivo. Results We found that transforming growth factor-?_1 (TGF-?_1 and transforming growth factor-?_2 (TGF-?_2) were up-regulated in stretched alveolar epithelial cells and also in serum of rats with large tidal volume ventilation. Tumor necrosis factor-? (TNF-?) had no effects on TGF-? production in alveolar epithelial cells. Exogenous H_ 2O_ 2, as an oxidant, increased TGF-? production in alveolar epithelial cells. NAC, an anti-oxidant, decreased stretch induced TGF-? production, along with a down-regulation of oxidant injury. NAC also blocked the up-regulation of TGF-? in in vivo model of VILI. Conclusion TGF-?_1 and TGF-?_2 were up-regulated in VILI. Oxidant injury mediated up-regulation of TGF-? in VILI. NAC, which attenuated oxidant injury and blocked TGF-? up-regulation in VILI, could be a future therapeutic strategy in VILI.

Objective To analyze clinical effectiveness of tigecycline for complicated intra abdominal infections (cIAIs) in surgical intensive care units.Methods The clinical data of patients diagnosed as cIAIs from Nov 2011 to Aug 2014 were retrospectively collected.Data of sex, age, severity of disease, bacterial strains and drug resistance, prior antibiotics, dosage of tigecycline were included.Results 1 862 patients were admitted into surgical intensive care unit from Nov 2011 to Aug 2014.54 patients were finally treated by tigecycline among 304 patients diagnosed as cIAIs.Acinetobacter baumannii (23.1％), Klebiella pneumonia (18.5％), Escherichia coli (16.9％) were the top three pathogenic bacteria.41/50 were of multiple bacterial infection.Previously adopted antibiotics were miscellaneous, the number of used antibiotics was up to 13 for one patient.Coverage of tigecycline averaged at 8.9 days.Tigecycline effective rate was 62％, 38％ (19/50) cIAIs were completely controlled and cured,24％ (12/50) patients showed effectiveness of tigercycline that procalcitonin decreased 50％ within 72 h.Logistic regression analysis showed that severity of disease and tigecycline dose contribute to the effectiveness within 72 h.Conclusions Tigecycline is effective alterative for patients diagnosed as complicated intra abdominal infections in surgical intensive care units.

Objective To study the effect of immunomodulation on improvement of immune function and prognosis in sepsis in rats,and its mechanism.Methods Experimental part: cecal ligation-perforation(CLP) models were divided into three groups including sham group(n=20),control group(n=20) and experimental group(n=20).Control group only used antibiotic and experimental group used antibiotic plus immunomodulation.Blood collections were made after CLP model at 3,12,48 and 72hr.Lymphocyte counting,CD4+,CD8+ T lymphocyte and CD4/CD8 ratio were checked.The apoptosis of lymphocyte in thymus and spleen and survival rate were checked.Clinical part: Prospective analysis of seventy patients who conformed to the sepsis standard.They were divided into two groups randomly.One was control group with regular therapy,and the therapy group with ulinastatin plus thymosin-?1 for 7days.The immune index before and after therapy at 0,1d,3d,and 7d was observed,including the clinical changes and survival data.Results Experimental part: Lymphocytes,CD4+ T lymphocytes and CD4/CD8 ratio in experimental group increased more significantly than in control group(P

Objective To observe the changes in serum vancomycin trough concentration,and explore its optimal dosage in critical patients.Methods A retrospective study was conducted.Data of 66 patients who used vancomycin during July 2010 to May 2012 in surgical intensive care unit (SICU) of the First Affiliated Hospital of Sun Yat-Sen University were collected and analyzed.According to the endogenous creatinine clearance rate (CCr),the patients were divided into two groups:CCr normal group (≥ 70 mL/min) and CCr lowered group (＜70 mL/min).The distribution of vancomycin serum trough concentration between two groups,relationship between vancomycin serum trough concentrations and CCr,and the influence of vancomycin serum trough concentrations on the prognosis was analyzed.The difference between actual dosage and the recommended dosage in guideline was compared between two groups.Results 119 times of vancomycin serum trough concentration in 66 patients were enrolled,and it was found that only 20.17％ (24/119) reached the target concentration (15-20 mg/L),45.38％ (54/119)＜ 15 mg/L and 34.45％ (41/1 19) ＞20 mg/L.Vancomycin serum trough concentration in CCr normal group (55 cases) was (13.11 ± 6.84) mg/L,among them 65.5％ (36/55) attained lower trough concentrations (＜ 15 mg/L).In the subgroup with 15-20 mg/L trough serum concentrations,vancomycin doses were significantly lower than that of recommendation (g/d:1.95 ± 0.61 vs.2.73 ± 0.32,F=1.739,P=0.001).Vancomycin serum trough concentration in CCr lowered group (64 cases) was (20.49 ± 8.12) mg/L,with 51.5％ (33/64) of them showed higher trough concentrations (＞20 rag/L).In the subgroup with 15-20 mg/L vancomycin trough serum concentration,vancomycin doses were higher than that of recommendation (g/d:1.08 ±0.49 vs.0.78 ±0.19,F=11.294,P=0.062).There was no significant difference in 28-day mortality between patients with targeting trough serum concentrations and those without [22.2％ (4/18) vs.18.8％ (9/48),x2=0.009,P=0.924].Serum creatinine [odds ratio (OR)=1.001,95％ confidence interval (95％CI):0.990-1.012,P=0.000],vancomycin doses (OR=0.600,95％CI:0.251-1.434,P=0.003),age (OR=0.985,95％CI:0.955-1.015,P=0.015) and body mass index (OR=1.013,95％CI:0.967-1.062,P=0.022) were found to be correlated to serum trough concentrations by multiple linear regression analysis.Conclusions The rate of vancomycin serum trough concentrations reaching the standard is low in critical patients,so constant monitoring is necessary.Creatinine,vancomycin dosage,age and body mass index show a relatively significant influence on the serum trough concentrations,and they should be taken into consideration in dosage to be given.

Objective To evaluate the ability of a synthetic PET/NIRF probe,named 18F-PSVue643,on the apoptosis detection in animal models with the anti-cancer drugs therapy,and compare the advantages and disadvantages between PET and NIRF.Methods Cell apoptosis was detected by MTT and flow cytometry in vitro.Established U87MG glioblastoma xenograft tumors in nude mice were treated with retinol and paclitaxel for nine days (for PET imaging) or eleven days (for NIRF imaging) continuously.The uptake values were recorded by ROI and expressed as ％ID/g.Results The apoptosis ratios in 10 and 100 nmol/L paclitaxel-treated groups were 7.4％ and 7.5％,respectively,and the apoptosis ratio of the control group was 4.3％.The apoptosis could be well detected by both NIRF and PET imaging during the whole process of treatment.However,the amount of probe for PET imaging was only a half of that for optical imaging to get the same apoptosis visualization.Conclusion 18F-PSVue643 is suitable for NIRF and PET imaging in detection of apoptosis,and it may be a promising agent for further clinical studies.

AIM: To study the protective effect of ethyl pyruvate(EP) on hepatocytes in septic mice.METHODS: The cecal ligation-perforation was made in mice as septic model.Ringer's ethyl pyruvate solution(REPS) and Ringer's lactic solution(RLS) were used to resuscitate septic mice.Anti-oxidative capacity of hepatic tissue and liver function were detected in different groups.RESULTS: Anti-oxidative capacity in septic mice was significantly lower than that in sham group(P

Objective To evaluate the diagnostic value of cerebrospinal lactate for the diagnosis of bacterial meningitis in patients post-neurosurgical operation (PNBM) with blood-contaminated cerebrospinal fluid (CSF). Methods A prospective observational study was conducted. 101 patients underwent neurosurgical operation and clinically suspected PNBM admitted to neurosurgical intensive care unit (NSICU) of the First Affiliated Hospital of Sun Yat-sen University from October 2015 to December 2016 were enrolled. Based on red blood cell quantitative test in CSF, the patients were divided into blood-contaminated and non blood-contaminated CSF groups. According to the PNBM diagnostic criteria of 2008 Centers for Disease Control and Prevention/National Healthcare Safety Network (CDC/NHSN), all patients were divided into PNBM group and non-PNBM group. The biochemical indexes levels in CSF were compared among the groups. Receiver operating characteristic (ROC) curve analysis was used to evaluate the diagnostic power of CSF lactate for PNBM in blood-contaminated patients.Results A total of 101 suspected PNBM patients were enrolled. In 77 blood-contaminated CSF patients, 39 patients were diagnosed as PNBM (account for 50.6%); in 24 non-blood-contaminated patients, 12 patients were diagnosed as PNBM (account for 50.0%). ① In non-PNBM patients, the lactate level in blood-contaminated CSF was significantly higher than that of non-blood-contaminated CSF (mmol/L: 3.5±1.3 vs. 2.3±1.1,P < 0.01). In PNBM patients, there was no significant difference in lactate level between blood-contaminated CSF and non blood-contaminated CSF (mmol/L: 6.8±2.1 vs. 6.9±2.5,P > 0.05). ② In both blood-contaminated and non blood-contaminated CSF, white blood cell (WBC), protein and lactate levels in PNBM group were significantly higher than those in non-PNBM group [WBC (×106/L): 660.0 (67.5, 1105.0) vs. 41.0 (15.0, 142.5) in blood-contaminated CSF,168.0 (86.5, 269.5) vs. 34.5 (7.0, 83.5) in non-blood-contaminated CSF; protein (mg/L): 4757.8 (2995.2, 10219.8) vs. 1292.8 (924.2, 1936.2) in blood-contaminated CSF, 39247.3 (14900.6, 62552.2) vs. 1441.6 (977.3, 2963.9) in non blood-contaminated CSF; lactate (mmol/L): 6.8±2.1 vs. 3.5±1.3 in blood-contaminated CSF, 6.9±2.5 vs. 2.3±1.1 in non blood-contaminated CSF, allP < 0.05], and glucose and CSF glucose/blood glucose ratio in PNBM group were significantly lower than those in non-PNBM group [glucose (mmol/L): 2.5±1.2 vs. 4.4±1.6 in blood-contaminated CSF, 1.9±1.4 vs. 3.4±0.9 in non blood-contaminated CSF; CSF glucose/blood glucose ratio: 0.28±0.15 vs. 0.46±0.16 in blood-contaminated CSF, 0.24±0.16 vs. 0.45±0.11 in non blood-contaminated CSF, allP < 0.01]. ③ It was shown by ROC curve analysis that CSF lactate level was a good diagnostic parameter for PNBM both in blood-contaminated and non blood-contaminated CSF, and the area under ROC curve (AUC) was 0.91 and 0.97, respectively. When the cutoff value of lactate in non blood-contaminated CSF was 3.35 mmol/L, the sensitivity was 100%, and the specificity was 91.7%. When the cutoff value of lactate in blood-contaminated CSF was 4.15 mmol/L, the sensitivity was 92.3%, and the specificity was 71.1%, and the combination of CSF lactate and glucose achieved better diagnostic specificity (AUC = 0.96, sensitivity was 97.4%, specificity was 84.2%).Conclusions Blood in CSF led to the elevation of CSF lactate as compared with that in non-blood-contaminated CSF of patients with PNBM. CSF lactate was still a good diagnostic parameter for PNBM both in blood-contaminated patients, and the combination of CSF lactate and glucose achieved better diagnostic specificity.