Résumé
Objective To investigate the protective effect of hesperidin on severe acute pancreatitis (SAP) in rats and its related mechanism.Methods Sixty male Sprague-Dawley (SD) rats were randomly divided into five groups (n = 12 in each group): sham group, SAP model group, dexamethasone group (5 mg/kg), low and high dose of hesperidin groups (10 mg/kg and 20 mg/kg). SAP rats were administered a retrograde infusion of 3.5％ sodium taurocholate solution into the biliopancreatic duct after laparotomy. Sham rats were administered with equivalent saline. The treatment was intravenously injected 5 minutes after operation through femoral vein. After 24 hours, the survival of animals was observed, the level of serum amylase, the volume of ascites and the relative specific gravity of the pancreas were measured; the pathological changes of pancreatic tissue were observed by Hematoxylin-eosin (HE) staining; the levels of serum and pancreatic tissue interleukin (IL-1β, IL-6) and tumor necrosis factor-α (TNF-α) were detected by enzyme linked immunosorbent assay (ELISA); the expression of Toll-like receptor 4 (TLR4), the phosphorylation of IL-1 receptor associated kinase (IRAK1) and nuclear factor-κB (NF-κB) were detected by Western Blot.Results Compared with SAP model group, the 24-hour survival rate were increased in low and high dose of hesperidin groups (83.3％, 100％ vs. 58.3％), the volume of ascites were reduced (mL: 7.36±0.91, 6.10±1.02 vs. 13.82±2.06), the levels of serum amylase were reduced (U/L: 1081.48±78.23, 1048.58±49.97 vs. 1990.37±127.27), the relative specific gravity of the pancreas were reduced [(7.52±1.02)％, (5.59±0.96)％ vs. (11.22±0.96)％], and the pathological damage of pancreatic tissue were reduced; the levels of serum and pancreatic tissue inflammatory factors were reduced in high dose hesperidin group [serum IL-1β (ng/L): 68.08±10.49 vs. 130.30±23.35, IL-6 (ng/L): 63.88±10.47 vs. 158.41±21.38, TNF-α(ng/L): 10.42±1.49 vs. 18.16±2.01; pancreas IL-1β (pg/μg): 13.87±1.84 vs. 20.08±1.66, IL-6 (pg/μg): 21.90±3.12vs. 38.13±3.57, TNF-α (pg/μg): 1.88±0.20 vs. 4.26±0.58]; the expression of TLR4, and the phosphorylation levels of IRAK1 and NF-κB were decreased in low and high dose of hesperidin groups (the sham operation group was 100, TLR4/β-actin: 91.9±15.6, 83.7±11.2 vs. 168.5±9.0, p-IRAK1/IRAK1: 117.4±7.6, 104.7±11.5 vs. 173.5±15.8, p-NF-κB p65/NF-κB p65: 119.9±9.3, 105.8±12.6 vs. 174.1±13.0), with statistically significant differences (allP < 0.05). The effects of dexamethasone were similar to that of high dose of hesperidin.Conclusions Hesperidin could significantly protect SAP rats, and this protection was related to the inhibition of TLR4/IRAK1/NF-κB signaling pathway, and to the reduction of pro-inflammatory cytokine expressions. The effect of high dose hesperidin (20 mg/kg) was more significant.
Résumé
Objective To explore the characteristic of early evaluation of patients with amplitude-integrated electroencephalogram (aEEG) on brain function prognosis after cardiopulmonary cerebral resuscitation (CPCR). Methods A retrospective analysis of the clinical data of patients with adult CPCR in intensive care unit (ICU) of Henan Provincial People's Hospital from March 2016 to March 2017 was performed. The length of stay, recovery time, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, aEEG and Glasgow coma scale (GCS) within 72 hours were recorded. The main clinical outcome was the prognosis of brain function (Glasgow-Pittsburgh cerebral performance category, CPC) in patients with CPCR after 3 months. Relationship between aEEG and GCS and their correlation with brain function prognosis was analyzed by Spearman rank correlation analysis. The effects of aEEG and GCS on prognosis of brain function were evaluated by Logistic regression analysis. The predictive ability of aEEG and GCS for brain function prognosis was evaluated by receiver operating characteristic (ROC) curve.Results A total of 31 patients with CPCR were enrolled, with 18 males and 13 females; mean age was (41.84±16.96) years old; recovery time average was (19.42±10.79) minutes; the length of stay was (14.84±10.86) days; APACHE Ⅱ score 19.29±6.42; aEEG grade Ⅰ(normal amplitude) in 7 cases, grade Ⅱ (mild to moderate abnormal amplitude) in 13 cases, grade Ⅲ (severe abnormal amplitude) in 11 cases; GCS grade Ⅰ (9-14 scores) in 7 cases, grade Ⅱ (4-8 scores) in 14 cases, grade Ⅲ (3 scores) in 10 cases; 19 survivals, 12 deaths; the prognosis of brain function was good (CPC 1-2) in 8 cases, and the prognosis of brain function was poor (CPC 3-5) in 23 cases. There was no significant difference in age, gender, recovery time, length of stay and APACHE Ⅱ score between two groups with different brain function prognosis, while aEEG grade and GCS grade were significantly different. Cochran-Armitage trend test showed that the higher the grade of aEEG and GCS, the worse the prognosis of CPCR patients (bothP-trend < 0.01). With the increase in GCS classification, the classification of aEEG was also increasing (r = 0.6206,P = 0.0003). Both aEEG and GCS were positively correlated with the prognosis of brain function (r1 = 0.7796,P1 < 0.0001;r2 = 0.7021,P2 < 0.0001). Univariate Logistic regression analysis showed that aEEG and GCS had significant effect on early brain function prognosis [aEEG: odds ratio (OR) = 37.234, 95％confidence interval (95％CI) = 3.168-437.652,P = 0.004, GCS:OR = 12.333, 95％CI = 1.992-76.352,P = 0.007]; after adjusting for aEEG and GCS, only aEEG had significant effect on the early prognosis of brain function (OR = 26.932, 95％CI = 1.729-419.471,P = 0.019). The ROC curve analysis showed that in the evaluation of the prognosis of CPCR patients with brain function, the area under ROC curve (AUC) of aEEG was 0.913, when the cut-off value of aEEG was 1.5, the sensitivity was 95.7％ and the specificity was 75.0％. The AUC of GCS was 0.851, the best cut-off value was 1.5, the sensitivity was 91.3％ and the specificity was 62.5％.Conclusion aEEG and GCS scores have a good correlation in the evaluation of brain function prognosis in patients with CPCR, the accuracy of aEEG in the early evaluation of the prognosis of patients with CPCR is higher than the GCS score.
Résumé
Objective To investigate the protective effect of hesperidin on severe acute pancreatitis (SAP) in rats and its related mechanism.Methods Sixty male Sprague-Dawley (SD) rats were randomly divided into five groups (n = 12 in each group): sham group, SAP model group, dexamethasone group (5 mg/kg), low and high dose of hesperidin groups (10 mg/kg and 20 mg/kg). SAP rats were administered a retrograde infusion of 3.5％ sodium taurocholate solution into the biliopancreatic duct after laparotomy. Sham rats were administered with equivalent saline. The treatment was intravenously injected 5 minutes after operation through femoral vein. After 24 hours, the survival of animals was observed, the level of serum amylase, the volume of ascites and the relative specific gravity of the pancreas were measured; the pathological changes of pancreatic tissue were observed by Hematoxylin-eosin (HE) staining; the levels of serum and pancreatic tissue interleukin (IL-1β, IL-6) and tumor necrosis factor-α (TNF-α) were detected by enzyme linked immunosorbent assay (ELISA); the expression of Toll-like receptor 4 (TLR4), the phosphorylation of IL-1 receptor associated kinase (IRAK1) and nuclear factor-κB (NF-κB) were detected by Western Blot.Results Compared with SAP model group, the 24-hour survival rate were increased in low and high dose of hesperidin groups (83.3％, 100％ vs. 58.3％), the volume of ascites were reduced (mL: 7.36±0.91, 6.10±1.02 vs. 13.82±2.06), the levels of serum amylase were reduced (U/L: 1081.48±78.23, 1048.58±49.97 vs. 1990.37±127.27), the relative specific gravity of the pancreas were reduced [(7.52±1.02)％, (5.59±0.96)％ vs. (11.22±0.96)％], and the pathological damage of pancreatic tissue were reduced; the levels of serum and pancreatic tissue inflammatory factors were reduced in high dose hesperidin group [serum IL-1β (ng/L): 68.08±10.49 vs. 130.30±23.35, IL-6 (ng/L): 63.88±10.47 vs. 158.41±21.38, TNF-α(ng/L): 10.42±1.49 vs. 18.16±2.01; pancreas IL-1β (pg/μg): 13.87±1.84 vs. 20.08±1.66, IL-6 (pg/μg): 21.90±3.12vs. 38.13±3.57, TNF-α (pg/μg): 1.88±0.20 vs. 4.26±0.58]; the expression of TLR4, and the phosphorylation levels of IRAK1 and NF-κB were decreased in low and high dose of hesperidin groups (the sham operation group was 100, TLR4/β-actin: 91.9±15.6, 83.7±11.2 vs. 168.5±9.0, p-IRAK1/IRAK1: 117.4±7.6, 104.7±11.5 vs. 173.5±15.8, p-NF-κB p65/NF-κB p65: 119.9±9.3, 105.8±12.6 vs. 174.1±13.0), with statistically significant differences (allP < 0.05). The effects of dexamethasone were similar to that of high dose of hesperidin.Conclusions Hesperidin could significantly protect SAP rats, and this protection was related to the inhibition of TLR4/IRAK1/NF-κB signaling pathway, and to the reduction of pro-inflammatory cytokine expressions. The effect of high dose hesperidin (20 mg/kg) was more significant.
Résumé
Objective To explore the characteristic of early evaluation of patients with amplitude-integrated electroencephalogram (aEEG) on brain function prognosis after cardiopulmonary cerebral resuscitation (CPCR). Methods A retrospective analysis of the clinical data of patients with adult CPCR in intensive care unit (ICU) of Henan Provincial People's Hospital from March 2016 to March 2017 was performed. The length of stay, recovery time, acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score, aEEG and Glasgow coma scale (GCS) within 72 hours were recorded. The main clinical outcome was the prognosis of brain function (Glasgow-Pittsburgh cerebral performance category, CPC) in patients with CPCR after 3 months. Relationship between aEEG and GCS and their correlation with brain function prognosis was analyzed by Spearman rank correlation analysis. The effects of aEEG and GCS on prognosis of brain function were evaluated by Logistic regression analysis. The predictive ability of aEEG and GCS for brain function prognosis was evaluated by receiver operating characteristic (ROC) curve.Results A total of 31 patients with CPCR were enrolled, with 18 males and 13 females; mean age was (41.84±16.96) years old; recovery time average was (19.42±10.79) minutes; the length of stay was (14.84±10.86) days; APACHE Ⅱ score 19.29±6.42; aEEG grade Ⅰ(normal amplitude) in 7 cases, grade Ⅱ (mild to moderate abnormal amplitude) in 13 cases, grade Ⅲ (severe abnormal amplitude) in 11 cases; GCS grade Ⅰ (9-14 scores) in 7 cases, grade Ⅱ (4-8 scores) in 14 cases, grade Ⅲ (3 scores) in 10 cases; 19 survivals, 12 deaths; the prognosis of brain function was good (CPC 1-2) in 8 cases, and the prognosis of brain function was poor (CPC 3-5) in 23 cases. There was no significant difference in age, gender, recovery time, length of stay and APACHE Ⅱ score between two groups with different brain function prognosis, while aEEG grade and GCS grade were significantly different. Cochran-Armitage trend test showed that the higher the grade of aEEG and GCS, the worse the prognosis of CPCR patients (bothP-trend < 0.01). With the increase in GCS classification, the classification of aEEG was also increasing (r = 0.6206,P = 0.0003). Both aEEG and GCS were positively correlated with the prognosis of brain function (r1 = 0.7796,P1 < 0.0001;r2 = 0.7021,P2 < 0.0001). Univariate Logistic regression analysis showed that aEEG and GCS had significant effect on early brain function prognosis [aEEG: odds ratio (OR) = 37.234, 95％confidence interval (95％CI) = 3.168-437.652,P = 0.004, GCS:OR = 12.333, 95％CI = 1.992-76.352,P = 0.007]; after adjusting for aEEG and GCS, only aEEG had significant effect on the early prognosis of brain function (OR = 26.932, 95％CI = 1.729-419.471,P = 0.019). The ROC curve analysis showed that in the evaluation of the prognosis of CPCR patients with brain function, the area under ROC curve (AUC) of aEEG was 0.913, when the cut-off value of aEEG was 1.5, the sensitivity was 95.7％ and the specificity was 75.0％. The AUC of GCS was 0.851, the best cut-off value was 1.5, the sensitivity was 91.3％ and the specificity was 62.5％.Conclusion aEEG and GCS scores have a good correlation in the evaluation of brain function prognosis in patients with CPCR, the accuracy of aEEG in the early evaluation of the prognosis of patients with CPCR is higher than the GCS score.
Résumé
Objective To investigate the influence of simvastatin treatment on Toll-like receptor 4 (TLR4) in monocytes of peripheral blood in patients with sepsis and severe sepsis and its significance. Methods A prospective randomized controlled trial was conducted. 106 patients with sepsis and 92 patients with severe sepsis admitted to Department of Critical Care Medicine of Henan Provincial People's Hospital from August 2013 to June 2015 were enrolled. These two groups of patients were randomized into conventional treatment group and simvastatin group. All patients received treatment according to the 2012 International Sepsis Treatment Guidelines, including anti-infection drugs, nutritional support, and palliative treatment, and the patients with severe sepsis were given early goal-directed therapy (EGDT). The patients in simvastatin group received simvastatin 40 mg daily orally for at least 15 days. The peripheral blood was collected and the monocytes were isolated at 1, 5, 10, 15 days after intensive care unit (ICU) admission. TLR4 expression on the surface of TLR4/CD14+ double positive monocytes was determined by flow cytometry, and adverse reaction was observed during treatment. Results TLR4 expression on the surface of monocytes showed a tendency of decreasing with prolongation of simvastatin treatment in the simvastatin group in patients with sepsis (n = 59) or severe sepsis (n = 54). However, in patients with sepsis, TLR4 level was significantly decreased from 10 days in simvastatin group as compared with that of conventional therapy group (n = 47), and it was decreased up to 15 days [mean fluorescence intensity (MFI): 21 (19, 28) vs. 27 (25, 33) at 10 days, Z = 2.198, P = 0.021; 16 (15, 21) vs. 26 (23, 34) at 15 days, Z = 4.611, P = 0.002]. In patients with severe sepsis, there was no significant difference in TLR4 level at different time points between simvastatin group and conventional treatment group (n = 38) [MFI: 55 (52, 63) vs. 56 (48, 65) at 1 day, Z = 0.313, P = 0.692; 47 (42, 56) vs. 49 (41, 58) at 5 days, Z = 0.827, P = 0.533; 40 (35, 42) vs. 42 (37, 45) at 10 days, Z = 1.012, P = 0.301; 33 (30, 38) vs. 38 (35, 41) at 15 days, Z = 0.539, P = 0.571]. No adverse reaction related with simvastatin was found during treatment in patients with sepsis or severe sepsis. Conclusions Statins could significantly down-regulate the TLR4 expression on peripheral blood monocytes in septic patients, while it showed no significant influence on TLR4 expression in patients with severe sepsis. A different effect of statins on TLR4 expression and the downstream inflammation process in sepsis and severe sepsis patients might partially explain the discrepancy in previous reports about the therapeutic effect of statins therapy in sepsis and severe sepsis patients.