1.Changes in plasma interleukin-33 concentration in sepsis and its correlation with seriousness of sepsisChang
Chinese Critical Care Medicine 2015;(2):138-142
ObjectiveTo observe the changes in plasma interleukin-33 (IL-33) in patients with sepsis and its regularity, the association between IL-33 and the infection, and the significance of IL-33 in predicting the prognosis of sepsis.Methods A prospective single-center single-blind clinical study was conducted. Forty patients with sepsis in intensive care unit (ICU) of Shengjing Hospital of China Medical University from May 2012 to January 2013 were enrolled. The patients were divided into general sepsis, severe sepsis and septic shock groups according to the severity of systemic infection and presence of organ dysfunction. The sepsis patients were again divided into 28-day death group and survival group. Ten healthy volunteers and 11 patients with systemic inflammatory response syndrome (SIRS) were enrolled as healthy control and SIRS groups. The levels of procalcitonin (PCT), IL-33, IL-6, IL-1β, tumor necrosis factor-α (TNF-α), and IL-33 receptor sST2 were determined with enzyme linked immunosorbent assay (ELISA) within 3 hours, and 24 hours and 5 days after enrollment to ICU. The acute physiology and chronic health evaluationⅡ (APACHEⅡ) score was calculated. The clinical outcome, length of stay in ICU, and duration of mechanical ventilation were recorded. The relationship between IL-33 and each parameter was analyzed by Spearman analysis. Receiver operating characteristic (ROC) curve was drawn to evaluate IL-33 in predicting the outcome of sepsis.Results Plasma IL-33 in sepsis patients within 3 hours after admission was significantly increased compared with that of the healthy controls and SIRS group (ng/L: 15.43±7.22 vs. 0.67±0.24, 1.25±1.09, bothP< 0.01). Compared with SIRS group, PCT in sepsis group was significantly increased [μg/L: 52.23 (19.69, 73.37) vs. 1.22 (0.69, 3.73),Z = -2.447,P< 0.001]. With exacerbation of illness, APACHEⅡ score, the values of PCT and IL-33 were gradually increased in general sepsis, severe sepsis and septic shock groups, while the length of stay in ICU and the duration of mechanical ventilation were gradually prolonged (P< 0.05 orP< 0.01). The concentration of IL-33 (ng/L) of sepsis patients admitted to ICU within 3 hours, and 24 hours and 5 days of the illness was 15.43±7.22, 11.82±6.16, 5.55±2.25, respectively (F = 4.823,P = 0.004). There was a positive correction between IL-33 within 3 hours after ICU admission and APACHEⅡ score (r = 0.351,P = 0.031), PCT (r = 0.412,P = 0.005), IL-6 (r = 0.535,P = 0.030), IL-1β (r = 0.674,P = 0.030), TNF-α (r = 0.250,P= 0.030), sST2 (r = 0.620,P< 0.001), and length of stay in ICU (r = 0.296,P = 0.013), duration of mechanical ventilation (r = 0.385,P = 0.011). Decreased plasma IL-33 level could be found in the survivors (n = 37,F = 7.798,P< 0.01), and its level in non-survivors (n = 3) was increased (F = 37.283,P> 0.05). The area under the ROC curve (AUC) of IL-33 and PCT in ROC curve were 0.821, 0.829. When the cut-off value of IL-33 was 13.79 ng/L, the sensitivity was 74.2%, the specificity was 79.6%; when the cut-off value of PCT was 4.70μg/L, the sensitivity was 87.5%, and the specificity was 81.4%.Conclusions The concentration of IL-33 3 hours after ICU admission was obviously increased in sepsis patients, and it was positively correlated with PCT, therefore it is valuable in the diagnosis of the infection. In addition plasma IL-33 is related to the severity of sepsis. Its trend of change is valuable in predicting the outcome and in distinguishing sepsis from SIRS.
2.Characteristics of Thromboelastography in Patients with Advanced Pregnancy Complicated with Severe Preeclampsia
Jia JIA ; Qiaoni YANG ; Zifang ZHAO ; Hanyu QIN ; Qiushi WANG ; Bin ZANG
Journal of China Medical University 2016;45(12):1105-1109
Objective To analysis the characteristics of thromboelastography and coagulation test in patients with advanced pregnancy combined with severe preeclampsia. Methods A retrospective single?center study was conducted. 35 patients with advanced pregnancy combined with se?vere preeclampsia who were admitted to hospital from January 2012 to December 2014 were analyzed compared to 43 third trimester patients with?out any complication. All the patients were treated based on the routine strategy. Blood sample were taken from the middle elbow vein to test blood cell count,serum biochemistry test,routine coagulation test and thromboelastography. All the results,including R,K,CI,α?angle and MA value, were compared between two groups. Analysis was performed to evaluate the correlation between all parameters of TEG and coagulation test. Re?sults There was no statistical significance between two groups in age ,prothrombin time and activated partial prothrombin time. In the severe pre?eclampsia group,the R value of TEG was increased(5.21±1.20 min vs 6.19±1.55 min,t=-3.144,P=0.002),α?angel was decreased(64.43°± 7.90° vs 60.37°±7.09°,t=2.367,P=0.02),and CI was decreased(0.81±2.27 vs-0.37±1.82,t=2.495,P=0.015). In blood cell count test,the platelets count was decreased in severe preeclampsia group[(217.48±65.68)×109/L vs(166.65±61.39)×109/L,t=3.500,P=0.001]. In routine coagulation test,only thrombin clotting time was increased in severe preeclampsia group(14.59±0.51 s vs 15.28±0.97 s,F=-3.800,P<0.001). In serum biochemistry test,the albumin was decreased in severe preeclampsia group(34.75±3.90 g/L vs 28.77±4.05 g/L,t=6.632,P<0.001),while serum urea nitrogen was increased(2.78±0.87 mmol/L vs 5.98±8.07 mmol/L,F=-2.333,P=0.026). In correlation analysis,thrombin clot?ting time had relationship between R(r=0.290,P=0.010),CI(r=-0.257,P=0.023)andα?angle(r=-0.243,P=0.032). Platelets count cor?related with CI(r=0.383,P=0.001),K(r=-0.409,P<0.001),α?angle(r=0.375,P=0.001)and MA(r=0.512,P<0.001). Conclusion For those who suffered from severe preeclampsia patients with advanced pregnancy,low coagulation function occurs in most of the patients com?pared to those patients without any complications. Thromboelastography may be helpful for those who have high risk factors ,especially with low platelets count and increased thrombin clotting time ,so as to reduce the incidence of bleeding or thromboembolic diseases.
3.The effects of preconditioning and postconditioning with isoflurane on focal cerebral ischemi/reperfusion injury in rats
Guofu LI ; Jia JIA ; Jiahong FU ; Haiyuan WANG ; Kaiqiang JI ; Bin ZANG
Chinese Critical Care Medicine 2014;26(6):431-435
Objective To investigate the effects of preconditioning and postconditioning with isoflurane on pro-inflammatory cytokines and lipid peroxidation in focal cerebral ischemic/reperfusion (I/R) injury in rats.Methods Thirty-two Sprague-Dawley (SD) rats were randomly divided into four groups:control group,model group,isoflurane preconditioning group and isoflurane postconditioning group,with 8 rats in each group.Rats in control group did not receive any challenge.In rats of model group right middle cerebral artery occlusion (MCAO) was conducted for 90 minutes.Rats in isoflurane preconditioning group received 2% isoflurane exposure for 30 minutes 24 hours before MCAO for 90 minutes.Rats in isoflurane postconditioning group were given 60-minute 2% isoflurane exposure after reperfusion of right MCAO.Twenty-four hours after the procedure,all rats were anesthetized with isoflurane,and blood sample taken from the heart was centrifuged,and the pro-inflammatory cytokines,including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α),and lipid peroxidation products such as malonaldehyde (MDA) and superoxide dismutase (SOD) were determined.The mRNA and protein expression levels of matrix metalloproteinase (MMP-2,MMP-9),tight junction protein Calaudin-5 and Occludin were determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western Blot.Results Compared with control group,serum levels of IL-1 β (ng/L),TNF-α (ng/L) and MDA (μmol/L) were elevated and activity of SOD (U/L) decreased in rats of model group (IL-1β:76.81 ± 11.14 vs.52.43 ± 8.86,TNF-α:64.93 ± 10.81 vs.33.64 ± 7.94,MDA:8.63 ± 1.42 vs.4.14 ± 0.98,SOD:0.95 ± 0.21 vs.2.36 ± 0.80,all P<0.05).After isoflurane preconditioning and postconditioning,compared with model group,the levels of IL-1 β,TNF-α and MDA were lowered,while activity of SOD was increased (IL-1 β:54.37 ± 9.06,56.82 ± 8.67 vs.76.81 ± 1 1.14,TNF-α:43.72 ± 6.16,39.49 ± 9.34 vs.64.93 ± 10.81,MDA:5.65 ± 0.83,5.82 ± 0.78 vs.8.63 ± 1.42,SOD:1.64 ± 0.47,1.71 ± 0.52 vs.0.95 ± 0.21,all P<0.05).Focal cerebral I/R injury could lead to an increased expression of MMP accompanied with a decreased expression of tight junction protein.Compared with model group,after isoflurane preconditioning and postconditioning,it was found that there were decreased mRNA and protein expression of MMP-2 and MMP-9 (MMP-2 mRNA:1.25 ± 0.08,1.32 ± 0.12 vs.2.48 ± 0.26,MMP-2 protein:1.56 ± 0.09,1.50 ± 0.08 vs.2.12 ± 0.11 ; MMP-9 mRNA:1.26 ± 0.13,1.20 ± 0.12 vs.2.74 ± 0.28,MMP-9 protein:1.53 ± 0.04,1.51 ± 0.05 vs.2.23 ± 0.09,all P<0.05) and increased levels of Calaudin-5 and Occludin (Claudin-5 mRNA:0.40 ± 0.08,0.38 ± 0.06 vs.0.28 ± 0.03,Claudin-5 protein:0.80 ± 0.06,0.81 ± 0.07 vs.0.39 ± 0.02; Occludin mRNA:0.54 ± 0.07,0.50 ± 0.08 vs.0.26 ± 0.06,Occludin protein:0.64 ± 0.06,0.69 ± 0.05 vs.0.49 ± 0.02,all P<0.05).Conclusion Preconditioning and postconditioning with isoflurane can lower the levels of pro-inflammatory cytokines and the degree of lipid peroxidation,and lower the hydrolytic activity of MMP to the tight junction protein in cerebral tissue,thereby decrease the loss of tight junction protein and alleviate I/R injury.
4.Correlation of mental health and personality of secondary nursing students in Xinjiang
Jing XIE ; Jin-Bao LIU ; Dong-Ze LI ; Li-Ping HUANG ; Jia-Bin ZANG
Chinese Journal of Modern Nursing 2011;17(29):3502-3504
Objective To know the mental health of secondary nursing students in Xinjiang and provide evidence for the psychological intervention.Methods 309 secondary nursing students in one health school were investigated with the general questionnaire,SCL-90 and EPQ.Results Compulsive symptoms rate in SCL-90was highest,and accounted for 72.5%.Average score in SCL-90 was (2.08 ± 0.56),and higher than national norm ( 1.75 ± 0.67) (t =10.25,P < 0.01 ).Every factor score of SCL-90 about the secondary nurses was higher than the national norm,and had statistical difference (P < 0.01 ). The girls,scores of depression (2.13 ±0.73),anxiety (2.08 ±0.72) and terrorist ( 1.93 ±0.74) were higher than boys [( 1.60 ±0.33),( 1.66 ± 0.52),( 1.42 ± 0.37 ) ],and the difference was significant ( t =- 5.54,- 2.12,- 4.68 ; P <0.05).The Uygur secondary nursing students,scores of somatization,coercion,depression anxiety and psychosis were higher and they have statistical differences (P < 0.05 ).There is a direct correlation between all dimensions of SCL-90 and nervousness and psychoticism of EPQ (P < 0.05 ),and were negative correlation with dissimulation ( P < 0.05 ).Conclusions The mental health status of Xinjiang secondary nursing students are bad,so these students need to be paid more attention to their mental health,especially female nursing students and minority nationality nursing students.
5.Regulatory effect of hemichannels protein Pannexin-1 on P2X7 receptor activity in the lungs of mice with lung injury
Na LI ; Jia JIA ; Xingmao WU ; Yang ZHAO ; Bin ZANG
Chinese Critical Care Medicine 2018;30(11):1071-1076
Objective To investigate the regulative effect of hemichannels protein Pannexin-1 on P2X7 receptor activation and caspase-1 mediated inflammatory response in the lungs of mice with lung injury. Methods Sixty male C57BL/6 mice were randomly divided into five groups with 12 mice in each group: sham operation group (Sham group), mechanical ventilation (MV) group, MV + low dose lipopolysaccharide (LPS) group (MLL group), MV + medium and high dose LPS group (MML group) and MV + high dose LPS group (MHL group). A "two-hit" lung injury model was reproduced by MV with high tidal volume combined with LPS injection in airway. All the mice underwent tracheotomy and intubation. After operation, the mice in Sham group were maintained spontaneous breathing, and those in other four groups were put on small animal ventilators to give MV with a large tidal volume of 28 mL/kg. After stable respiration in mice, those in the Sham group and MV group were injected 8 mL/kg of normal saline (NS) into the airway, and those in MLL, MML and MHL groups were given 2, 5 and 8 mg/kg of LPS respectively (diluted with NS into 8 mL/kg). After 4 hours on MV, the mice were sacrificed, and bronchoalveolar lavage fluid (BALF) was extracted to determine intracellular and extracellular ATP concentration. Lung tissue was harvested and water containing ratio of lungs was measured. The degree of lung pathological damage was observed after hematoxylin-eosin (HE) staining, and lung injury score was calculated. The expression of Pannexin-1 protein in lung tissue was calculated with immunohistochemistry. Western Blot and fluorescence quantitative reverse transcription-polymerase chain reaction (RT-qPCR) were used to detect the protein and mRNA expressions of Pannexin-1, P2X7 receptor, caspase-1 and interleukin-1β (IL-1β). Results There was no obvious pathological change in lung tissue in Sham group, intracellular ATP concentration was higher than extracellular ATP concentration, water content in lung tissue was lower, Pannexin-1 expression was low in lung tissue by immunohistochemical staining, and Pannexin-1, P2X7 receptor, caspase-1 and IL-1β were only expressed in micro-protein and mRNA in lung tissue. Compared with the Sham group, the alveolar lesions and hemorrhages in the MV group were not obvious, and lung injury score was slightly increased. There was no significant fluctuation between intracellular ATP concentration and extracellular ATP concentration. The water content in lung tissue was increased significantly, while the expressions of Pannexin-1, P2X7 receptor, caspase-1 and IL-1β in lung tissue were increased slightly. After LPS intervention, progressively increased lung exudation, ruptured alveoli, dilated capillaries, and inflammatory cells were found, and lung injury score was increased without significant difference among the three LPS doses groups. With the increase in LPS dosage, the concentration of extracellular ATP in BALF was increased, the concentration of intracellular ATP was decreased, the water containing ratio of lung tissue was increased gradually, and the protein and mRNA expressions of Pannexin-1, P2X7 receptor, caspase-1 and IL-1β in lung tissue were increased gradually in a dose-dependent manner. The parameters in MHL group showed significant differences as compared with those in MV group [lung injury score: 8.25±0.45 vs. 3.50±0.52; intracellular ATP concentration (μmol/L): 198.76±150.77 vs. 896.69±281.11, extracellular ATP concentration (μmol/L): 336.57±90.28 vs. 141.52±42.22; lung water containing rate: (6.37±0.11)% vs. (5.05±0.14)%; Pannexin-1 protein (gray value): 3.20±0.70 vs. 1.54±0.76, Pannexin-1 mRNA (2-ΔΔCT): 7.86±0.86 vs. 2.47±0.92; P2X7 receptor protein (gray value): 3.18±0.88 vs. 1.80±0.72, P2X7 receptor mRNA (2-ΔΔCT): 7.17±0.96 vs. 2.31±0.45; caspase-1 protein (gray value): 3.00±0.45 vs. 0.93±0.51, caspase-1 mRNA (2-ΔΔCT): 4.39±0.91 vs. 2.74±0.41; IL-1β protein (gray value): 2.54±1.08 vs. 1.16±0.53, IL-1β mRNA (2-ΔΔCT): 132.34±41.48 vs. 19.67±8.67; all P < 0.05]. Conclusion Pannexin-1 may be involved in LPS and MV induced lung injury, which may be regulated by intracellular release of ATP to the extracellular site and binding to P2X7 receptor on the cell surface, thereby regulating active caspase-1 production and release, involving in the production of IL-1β and other inflammatory factors eventually which leads to the occurrence and development of lung injury.
6.An experiment on the pathogenesis of early biotrauma in ventilator-induced lung injury
Jia JIA ; Na LI ; Guofu LI ; Bin ZANG
Chinese Critical Care Medicine 2018;30(9):861-866
Objective To investigate the pathogenesis of early biotrauma in ventilator-induced lung injury (VILI).Methods Twenty-four 8-week-old male specific-pathogen-free Sprague-Dawley (SD) rats weighing 250-300 g were randomly divided into sham group (S group), conventional mechanical ventilation group (L group) and high tidal volume (VT) mechanical ventilation group (H group) with 8 rats in each group. All rats received tracheostomy after anesthesia. Rats in S group received no mechanical ventilation but breathe room air spontaneously. All other parameters of the ventilator were the same in both mechanical ventilation groups, and the fraction of oxygen was set to 0.21, the rats in L group received 7 mL/kg VT, and those in H group received 28 mL/kg VT. Four hours after ventilation all rats were sacrificed and the lung tissues were harvested for wet/dry (W/D) ratio. Pathological injury score was evaluated by hematoxylin and eosin (HE) staining. Transferase-mediated deoxyuridine triphosphate-biotin nick end labeling stain (TUNEL) was performed to count the apoptosis cell in lung epithelial. Western Blot was performed to evaluate hemi-channel protein Pannexin-1 expression in lung homogenate. Bronchoalveolar lavage fluid (BALF) was collected, and the concentration of lactate dehydrogenase (LDH), isoprostane, adenosine triphosphate (ATP) and white cell count in BALF were measured. Yo-pro-1/propidium iodide (PI) double stain was performed to evaluate early apoptosis cell in BALF.Results There was no significant difference in lung injury between S group and L group. Compared with S group and L group, rats in H group showed significant lung injury, represented as alveolar rupture, inflammatory cell infiltration, interstitial edema and airway epithelial exfoliation, and the lung W/D ratio was increased significantly (5.1±0.2 vs. 4.4±0.2, 4.3±0.4, bothP< 0.01), pathological score was significantly increased [4.00 (4.00, 8.00) vs. 1.00 (0, 4.00), 2.00 (0, 4.75), bothP< 0.01], the white cell in BALF was significantly increased (×106/L: 2.97±0.46 vs.1.03±0.26, 0.79±0.19, bothP< 0.01), the level of LDH was significantly increased (U/L: 148.6±38.2 vs. 34.4±13.5, 78.6±13.9, bothP< 0.01), and the expression of Pannexin-1 in lung homogenate was significantly increased (Pannexin-1/GAPDH: 0.89±0.21 vs. 0.48±0.25, 0.61±0.17, bothP< 0.01), the ATP concentration in BALF was also significantly increased (nmol/L: 456.84±148.72 vs. 19.23±13.34, 113.26±57.90, bothP< 0.01). There was no significant difference in the apoptosis cell in lung tissue or the apoptosis cell rate, isoprostane level in BALF among the three groups [apoptosis cell in lung (cells/HP): 4.00 (3.00, 5.00) vs. 5.00 (4.00, 6.00), 4.00 (3.25, 6.00); apoptosis cell rate in BALF: (0.57±0.20)% vs. (0.42±0.16)%, (0.58±0.19)%; isoprostane in BALF (μg/L): 3.85±0.46 vs. 3.83±0.60, 3.59±0.69, allP > 0.05].Conclusion The early pathogenesis of biotrauma in VILI is related to the release of inflammation mediator via membrane channel after activating by pressure stress, but not apoptosis and lipid peroxidation.
7.The role of PCSK9 on lipid accumulation and injury in the kidney of C57BL/6 mice
Meiyan WU ; Chongsen ZANG ; Fuzhe MA ; Bin CHEN ; Weixia SUN ; Mindan SUN ; Hang YUAN ; Zhonggao XU ; Ye JIA
Chinese Journal of Nephrology 2018;34(11):845-850
Objectives To evaluate the role of PCSK9 (proprotein convertase subtilisin kexin type 9) on the lipid accumulation and kidney injury of C57BL/6 mice. Methods The 24 h urine of 12 weeks old wide type C57BL/6 mice and PCSK9 knockout (KO) mice were collected through a metabolic cage, followed by perfusion and sacrifice. Urinary microalbumin?to?creatinine ratio (UACr), total cholesterol and triglyceride in kidney tissues were measured by ELISA. BODIPY 493/503 staining and standard transmission electron microscopy (TEM) of kidney tissues was performed for evaluating lipid accumulation and podocyte foot effacement in the kidney. Kidney tissues were also evaluated by PAS stain and TUNNEL stain. PCSK9, podocin and nephrin were quantified through real?time PCR, and the Bcl?2, Bax and cleaved caspase 3 were evaluated by Western blotting. Results Total cholesterol and triglyceride contents were higher in the kidneys of PCSK9 KO mice than controls (P<0.05). The level of lipid accumulation in glomeruli and tubules through BODIPY 493/503 stain, and the amount of lipid drop in TEM were more serious in PCSK9 KO mice. UACr and podocyte foot process effacement were increased, and the transcription of podocin and nephrin were decreased in the kidneys of PCSK9 KO mice (all P<0.05). The expression of Bcl?2 was decreased, and Bax and cleavedcaspase 3 were increased in the kidney samples of PCSK9 KO mice. Conclusion PCSK9 might be reversely involved in lipid homeostasis and accumulation, resulting in injury and apoptosis in the kidneys of C57BL/6 mice.
8. Recent studies on the correlation of vitamin B12 and diabetes
Bin HU ; Pu ZANG ; Zhan-hong GUO ; Jia-qing SHAO
Journal of Medical Postgraduates 2019;32(3):303-306
Vitamin B12 (VitB12) is one of the essential vitamins in humans and is involved in DNA synthesis and cellular metabolism. Many studies have shown that the lack of VitB12 is closely related to the occurrence and development of diabetes and its complications. Therefore, regular testing and reasonable supplementation of VitB12 can help prevent diabetes complications. The article reviews the relationship between VitB12 and diabetes as well as the application of VitB12 in diabetic patients.