There is overwhelming evidence for an involvement of reactive oxygen species(ROS) in the pathogenesis of atherosclerosis(AS) in diabetes mellitus(DM). For many years, knowledge on the contribution to diabetic complications and vascular disease induced by advanced glycation end-products(AGEs)has been rising. During the development of atherosclerosis, AGEs and ROS might have interaction. In this article, we provided four angles of view to discuss the role of ROS in the pathogenesis of atherosclerosis: the chemistry of ROS, the effect of vascular targets of ROS on activity of AGEs, the role of ROS in the pathogenesis of atherogenesis by AGEs, the same effect of ROS and AGEs-transcriptional regulation. [

ObjectiveTo investigate the influence of the midazolam sedation based on remifentanil analgesia on the occurrence of delirium in critically ill patients in intensive care unit (ICU).Methods A single-center prospective randomized controlled trial was conducted. 140 consecutive critically ill patients admitted to ICU of Peking University People's Hospital, undergoing mechanical ventilation longer than 24 hours, with the need of sedation, from February 2014 to January 2015 were enrolled. They were randomly divided into two groups by computer generated random numbers table, eachn = 70. The patients in observation group received midazolam 1μg·kg-1·min-1 for sedation, and 1 mg/mL remifentanil for analgesia with 0.05 mg/kg intravenous bolus, then continuous infusion of 0.02-0.10 mg·kg-1·h-1. The patients in control group received midazolam for sedation only. The data were recorded as follows: the main indices for observation included the occurrence of delirium and its duration; the second item for observation was consumption of drug for sedation, followed by the mean arterial pressure (MAP) before and after sedation, the time of wake-up, duration of mechanical ventilation, the length of ICU stay, and 28-day fatality rate. The 28-day survival was analyzed by Kaplan-Meier survival curve.Results The dosage of remifentanil used in observation group was (98.6±24.9) mg/d, the dosage of midazolam was significantly lower than that of the control group (mg/d: 160.6±33.3 vs. 178.9±43.4, t = 2.829,P = 0.005), the incidence of delirium was obviously lower than that of the control group [22.9% (16/70) vs. 57.1% (40/70),χ2 = 15.700,P< 0.001], and the time of delirium was slightly shorter than that of the control group (hours: 162.9±78.0 vs. 194.8±117.3,t = 0.947,P = 0.348). Among the patients with delirium, the dosage of dexmedetomidine used in observation group was significantly less than that of the control group (mg/d: 0.54±0.11 vs. 0.64±0.14,t = 2.112,P = 0.041). The MAP before sedation was similar as the MAP after sedation in both groups, and there was no significant difference between observation group and control group [mmHg (1 mmHg = 0.133 kPa), before treatment: 84.7±16.2 vs. 89.5±37.7, after treatment: 82.3±10.7 vs. 80.8±13.9, bothP> 0.05]. There was no significant difference in the time of waking-up between observation group and control group (hours: 2.3±0.9 vs. 2.4±0.8,t = 0.487,P = 0.627). The duration of mechanical ventilation (hours: 143.4±138.3 vs. 163.9±158.9, t = 0.812,P = 0.418), the length of ICU stay (days: 8.8±7.7 vs. 10.0±7.8,t = 0.917,P = 0.361) and 28-day fatality rate [11.4% (8/70) vs. 20.0% (14/70),χ2 = 1.941,P = 0.245] in observation group were slightly lower than those of the control group without significant difference. Kaplan-Meier survival curve showed that the cumulative 28-day survival rate in observation group was slightly higher than that of control group (χ2 = 1.647,P = 0.199). ConclusionAnalgesia based on sedation may reduce the occurrence of delirium and its severity, furthermore, even if delirium occurs, it may be less severe.

OBJECTIVE To investigate the role of cinnabar and realgar in Angong Niuhuang Wan (AGNH) -produced neuroprotection against lipopolysaccharide ( LPS) -mediated neuronal damage and further explore the corresponding mechanisms. METHODS Primary rat midbrain neuron-glia cultures were used as an in vitro model to investigate effects of AGNH on LPS-mediated degeneration of dopamine (DA) neurons. The experiment was divided into normal control group, LPS model group, LPS + cinnabar (4 and 40 mg·L-1) groups, LPS + realgar (4 and 40 mg·L-1 ) groups and LPS + AGNH (40 and 400 mg·L-1 ) group. Drugs were added 30 min before LPS treatment. After 7 d, dopaminergic neurotoxicity was assessed through the quantification of tyrosine hydroxylase (TH)-positive neurons and morphological analysis of TH-positive neurons; the activation of microglia was evaluated using OX-42 antibody; the gene expression of tumor necrosis factor-α (TNF-α) and induced nitric oxide synthase (iNOS) mRNA in microglia was performed by real-time RT-PCR analysis, and the release of TNF-α and nitric oxide (NO) in the supernatant of neuron-glia cultures was determined respectively by the ELISA and Griess reagent. RESULTS Compared with normal control group, DA neurons in LPS model group decreased by 40% (P <0.05) , microglial activation was induced, the expression of TNF-α mRNA and iNOS mRNA in microglia increased 9 and 2 times, respectively ( P < 0. 05 ) , and subsequent production of TNF-α and NO in the supernatant of neuron-glia cultures increased 20 and 30 times, respectively (P<0.05). Compared with LPS model group, AGNH 400 mg·L-1 and realgar 40 mg·L-1 significantly attenuated LPS-mediated DA neuronal loss by 40% and 30% , respectively (P<0.05) and inhibited activation of microglia and expression of TNF-α mRNA by 61% and 52% (P <0.05). iNOS mRNA was reduced by 58% and 51% (P <0.05 ) in microglia. The subsequent release of TNF-α was reduced by 55% and 43% (P<0.05) and NO reduced by 53% and 34% (P<0.05) in the supernatant of neuron-glia cultures. Cinnabar had no inhibitory effect on LPS-induced changes. CONCLUSION AGNH protects LPS-induced neurotoxicity through its anti-inflammatory properties and realgar might be the key contributor to the neuroprotective action of AGNH, while cinnabar fails to show any neuroprotection.

Objective:To establish an efficient method for expression and purification of vMIP-Ⅱ which encoded by a viral gene and ho-mogued human chemokine in active single strand in E.coli cells. Methods: Cloning with bi-enzyme restriction and lysising bacteria with cold osmoic shock were used for expression,MBP affinity chromatography of fusion protein and self-selective of recombinative peptide for final purification. The expressing and purifying products were detected with SDS-PAGE and Western blotting and identified with inhibitory adhesion experiment for its activity.Results: Fusion protein MBP-vMIP was effeciendy expressed in E. coli at secretive type, and self-cleaved to sparate the vMIP-Ⅱ. The final product single strand vMIP-Ⅱ was active for blocking chemokine receptor CCR5.Conclusion:This is an effective method for obtaining viral chemokine vMIP-Ⅱ of recombinant single strand.The recombinant vMIP-Ⅱ may be useful for the study of diseases involving in chemokiine receptors such as HIV infection,rejection of transplantation and chronic inflammation,etc.

Objective To detect the expression of IL-23 receptor in T lymphocytes and NK cells in peripheral blood mononuclears(PBMC)from patients with inflammatory bowel disease(IBD)as well as its significance in the pathogenesis.Methods PBMC,isolated from 30 patients with UC,16 patients with CD and 30 healthy controls,were used to determine the expression of IL-23 receptor in T lymphocytes and NK cells by flow cytometry.The surface of lymphocytes was determined by three-colour flow cytometry in inflammatory bowel disease patients,and the results were compared with those of normal peripheral blood.Results The expression of IL-23R on peripheral CD4+ T,CD8+ T and CD56+ NK cells of patients was obviously higher than that in the control group.Conclusion The expression of IL-23R on T lymphocytes and NK cells of patients with IBD was increased,suggesting that IL-23 receptor plays an important role in the pathogenesis of IBD.

Objective To explore effects of human embryonic stem cells ( hESCs) on proliferation, invasion and migration of SK-Hep1 human hepatoma cells in the co-culture of micro environmen of hESCs and SK-Hep1 . Methods Single cultured SK-Hep1 cells were served as control group while SK-Hep1 which non-contact co-cul-tured with hESCs was regarded as experimental group .The proliferation ability of SK-Hep1 was measured by MTT method; invasion and migration ability of SK-Hep1 cells were detected by Transwell chamber method;the nucle-us variation and cell apoptosis of SK-Hep1 were detected by Hoechst33258 chromosome and flow cytometry. Results The proliferation of SK-Hep1 cells in the experimental group was obviously inhibited as compared with control group ( P<0.05 );the number of SK-Hep1 cells which passed through the Transwell chambers were sig-nificantly reduced as compared with control group in invasion and migration experiment ( P <0.05 ); more nucleus pycnosis and deformation appeared in experimental group than that in control group .And apoptosis rate of SK-Hep1 cells in the experimental group was significantly higher than that of in the control group ( P<0.05 ) .Conclusions Human embryonic stem cells have inhibitory effect on human hepatoma cell line SK-Hep1 .

Objective: To observe influence of exercise on expressions of peroxisome proliferators-activated receptor-γ (PPAR-γ) and glucose transporter-4 (Glut-4) in skeletal muscle tissue of mice with insulin resistance (IR) induced by high fat diet, and preliminarily investigate mechanism of swimming training improves IR. Methods: A total of 30 eight-week-old healthy male C57BL /6J mice were randomly divided into normal diet group (n=10), high fat diet group (n=10) and high fat diet + exercise group (HE group, n=10, mice received 12-week swimming training). Body weight and fasting blood glucose (FBG) of mice were measured every week. After 12-week swimming training, fasting insulin (FINS) was measured by radioimmunoassay and IR index (IRI) was calculated; expressions of PPAR-γ and Glut-4 mRNA in skeletal muscle tissue were detected by reverse transcription polymerase chain reaction (RT-PCR). Results: Compared with normal diet group, body weight significantly increased in high fat diet group; body weight of HE group was significantly lower than that of high fat diet group (P<0.05). Compared with normal diet group, there were significant increase in FINS, FBG and IRI in high fat diet group and HE group (P<0.01). Compared with high fat diet group, there were significant decrease in FINS [(14.00±7.12) mmol/L vs. (10.17±3.88) mmol/L], FBG [(9.49±1.28) mmol/L vs. (8.03±1.67) mmol/L] and IRI [(1.47±0.38) vs. (1.06±0.27), P<0.05 all], and significant increase in expressions of PPAR-γ [(0.95±0.17) vs. (2.37±0.41)] and Glut-4 mRNA [(0.68±0.24) vs. (1.54±0.28), P<0.01 both] in HE group. Conclusions: Exercise may significantly improve insulin resistance, and the mechanism may be related with upregulation of expressions of PPAR-γ and Glut-4 mRNA in skeletal muscle, regulation of glucose metabolism and promotion of transduction of insulin signal.

Objective To evaluate the efficacy and safety of endoscopic submucosal excavation (ESE) and submucosal tunneling endoscopic resection (STER) for gastroesophageal junction (GEJ)submucosal tumors (SMTs) originating from the muscularis propria(MP) layer.Methods Clinical data of sixty-one patients with GEJ SMTs originating from the MP layer who were treated with ESE(ESE group,n=39) or STER(STER group,n=22) between January 2013 and December 2015 in Changhai Hospital were retrospectively analyzed.Outcomes and complications in the two groups were compared.Results Single lesion in 61 patients were all resected by therapeutic endoscopy successfully.Operation time in the STER group was shorter than that of the ESE group(47.27±20.89 min VS 66.56±40.07 min,P＜0.05).There was no significant difference in number of hemostatic clips between the two groups[7.10±5.57 VS 8.00± 1.88,P＞0.05].Hospitalization time of STER group was shorter than that of the ESE group [3.0(1.25) d VS 4.0 (1.00) d,P＜0.05].One patient developed delayed hemorrhage in ESE group,while no other complications occurred in either group.The wound healed in both groups under gastroscopy,and no residual or recurrent tumors were detected during the follow-up period.Conclusion Both STER and ESE can be used for GEJ SMTs originating from the MP layer,but STER is more safe and efficient.

Objective To explore the mechanism of vessel endothelial dysfunction in rats under intermittent hypoxia (IH). Methods The respiratory simulation system was used to simulate IH. Sixty C57BL/6J rats (male) were randomized into control group and IH group. The rats of IH group were exposed to IH 8 hours per day for 6 weeks. The serum levels of hypoxia inducible factor (HIF)-1a and stromal cell derived factor (SDF)-1a were assessed by ELISA. The serum levels of reactive oxygen species (ROS) were detected in two groups. The serum expression of miR-199a-5p was detected by real-time fluorescent quantitative PCR in two groups. The dual luciferase report system and point mutation test were used to verify target gene for HIF-1a. Results The serum levels of HIF-1a and SDF-1a were significantly higher in IH group than those of control group (μg/L:1.60±0.02 vs. 1.19±0.02, 1 823.00±8.97 vs. 1 444.00±17.90, P<0.01). The serum level of ROS was significantly higher in IH group than that of control group (U/mL:487.66±35.73 vs. 211.57±23.82, P<0.01). The serum level of miR-199a-5p expression was significantly lower in IH group compared to that of control group (1.31±0.07 vs. 3.47± 0.17, P<0.01). The result of dual luciferase reporter gene detection confirmed that target gene of miR-199a-5p was HIF-1a. Conclusion The serum level of miR-199a-5p is decreased first due to IH, and then its target gene (HIF-1a) is increased. HIF-1a can induce the increased level of SDF-1a, and its receptor (CXCR-4 ) is also increased. Finally, HIF-1a can increase the serum level of ROS, resulting in the endothelial dysfunction.

Objective To explore the biomechanis with different bone density by the pedicle screws fixation before and after fatigue test.Thus provide biomechanical basis for the clinical work.Methods A total of 27 fresh lumbar vertebrae samples of adult sheep (L1-L5) were equally divided into three groups,such as group A of decalcified with HCL 0 h,group B of decalcified with HCL 2 h and group C of decalcified with HCL 4 h,by using the random number table method,every groups was 9 models.Four screws was performed on the L4-L5 pedicle of vertebral arch of the three groups.Three groups were performed fatigue test of 250 000 times in 4 direction (flexion,extension,left lateral bending,right lateral bending) by (300+ 105) N load.The range of motion(ROM),the axial compressive stiffness were measured and the results in every group were compared before and after fatigue test.Results After fatigue test,ROM and the axial compressive stiffness had no significant change in group A (P＞0.05),but ROM of B group and C group were both increased and the axial compressive stiffness were decreased,Significance was found with and between groups.Conclusion The stability of people who are performed pedicle screws simplly may be decrease when the spine of osteopenia.