Objective To investigate the mechanism of cytokines in brain pathologic changes caused by lipopolysaccharide(LPS).Methods A rat model of LPS was established by injection with a dose of 5mg/kg LPS into thigh vein.60 SD rats were randomly divided into three groups:control group,LPS group,naloxone+LPS group,each group included 20 rats and was subdivided into 4 subgroups(1h,2h,4h,6h respectively).In each subgroup,cerebral pathological changes and concentrations of TNF-α,IL-1β,IL-6 in brain homogenate were investigated.Results Brain homogenate concentration of TNF-α in subgroup LPS 2h was higher than control group[(9 30±0.57) ng/g vs(8.00±0 79)ng/g,P＜0.01],other subgroups have no significant difference from control group. Naloxone group had lower TNF-α level than LPS group.Brain homogenare concentration of IL-1β in subgroup LPS 1h increased apparently[(0.56±0.08)ng/g,P＜0.01],subgroup LPS 2h had no significant change;other subgroups have no significant difference from control group.Natoxone group had lower IL-1β level than LPS group(P＜0.01).but no difference from control group.Brain homogenate concentration of IL-6 in subgroup LPS 2h and 4h were respectively(459.68±79.15)ng/g,(816.07±111.31)ng/g,significantly higher than control group[(377.22±63.73)ng/g,(369.98±34.35)ng/g,respectively].Control group had no significant cerebral pathologic changes,while LPS group showed apparent changes:edema,interstitial substance and mening vessels expanding and hyperaemia,neurosome minification,Nissl's body lost,karyopycnosm,and nucleoli abolition.Naloxone group had lighter neurocyre injuries and brain edema,especially at 2h and 4h.Conclusions After LPS injection,the level of cytokines changed as time goes by,and this fits the brain pathologic changes.Naloxone has protecnve effect on brain tissue in LPS treated rats.Inflammatory cytokines play an important role in the mechanism of cerebral damage in LPS rats.

To investigate the electrophysiologic characteristics of f-wave amplitude and to evaluate its role in development and persistence of chronic atrial fibrillation (AF) associated with rheumatic heart disease (RHD). Methods: Epicardial mapping was performed in 44 patients with chronic AF of RHD who underwent heart valve surgery. Ten patients with supraventricular tachycardia served as the control group. Results:The f-wave amplitude of left atrium (LA) and middle and low LA posterior regions were significantly lower than those of the control group. The f-wave amplitudes of the upper, middle and low sections in LA posterior region were significantly lower than those in right atrium (RA) (P<0.05). The f-wave amplitudes were compared before and after electrocardioversion in 14 patients with chronic AF. The mean atrial electrogram amplitude during sinus rhythm was significantly higher than that during AF (P<0.01).The f-wave amplitude in left appendage was higher than that in LA posterior region (the upper,middle and the lower part),P<0.05.The f-wave amplitude in the upper section of LA was significantly higher than that in the middle section. The f-wave amplitude in AF group was not correlated to the diameter or volume of both atria. Conclusion: There are amplitudes differences between the upper, middle and lower LA,suggesting that the middle and lower sections of LA posterior wall may be the region producing anisotropy and reentrant circle.

Background and purpose: Reports showed that berbefine not only had an effect ofdetoxification and inflammation but also could induce the cell to apoptosis. Berberine may also inhibit the migration and metastasis of tumor. To investigate the effects and mechanism of berberine on migration and metastasis of A549 cells, the proliferation, mobility and adhesion of A549 cells were observed after incubation with berberine. Methods: The proliferation was determined by MTT. Wound healing assay and adhesion test were used to observe the mobility and adhesion rate. The mRNA and protein expressions of MMP2 and MMP9 were assessed by semi-quantitive RT-PCR and gelatin zymography, respectively. Results: Berberine could significantly inhibit the proliferation ofA549 within a certain range of treating time and dose (P<0.05). The mRNA and protein expression of MMP2 and MMP9 gene were decreased slightly by the treatment ofberberine (P<0.05), especially at dose of 100 μg/ml. Conclusion: Berberine can inhibit the migration and adhesion abilities of A549 cells, probably by down-regulating the expression and activation of MMP2 and MMP9.

Indexes of cardiovascular function and survival time were obser-vedin rats given the following antagonists respectively after scald injury: anti-p-endorphin serum at 10?l, Naloxone at 2mg, ICI174864 at 0.2mg, or TRH at 2 mg, and half of the doses were administered at 1, 2, 3h after scald. The results showed that the cardiac indexes (dP/dtmax, -dP/dtmax and LVSP)were improved, the decrease of mean arterial pressure ( MAP ) and heart rate ( HR ) were delayed after the injections of anti-p-endorphin serum, naloxone or ICIi748e4, and survival time was significantly prolonged in anti ? - endorphin serum group. TRH had little effect on cardiac indexes, MAP and HR were maintained at high level at earlier period, but sharply sloped down in about 210 min after burn. The result suggests that intraventri-cular administration of anti-?-endorphin, naloxone or ICI174864 had much benefit on scald shock, but TRH was uncertain at least in the treatment of scald shock.

Methods including stimulation, cauterization, of nuclei and measurement of pain threshold were used to clarify the role of paraventricular nucleus of hypothalamus (PVH) in pain regulation. Results showed that electrical or L-glutamate sodium stimulation of PVH could elevate the pain threshold in the rat dose-dependently, electrical cauterization of PVH could reduce the pain threshold; and removal of the pituitary gland could not influence the effect of L-glutamate sodium on pain threshold. These results suggest that PVH may play an important role in pain regulation.

The immune function of rats was markedly suppressed following burn injury. At 24 h after burn, the lymphoproliferative response to Con A and IL-1 and IL-2 production in burned rats were significantly reduced, as compared with control animals. At 72 h after burn the immune parameters as above were at the lowerest levels. At 120 h after burn, a slight elevation of immune function was observed, but still lower than the levels of controls. The results of radioimmunoassay of ?-endorphin and dynorphin A in plasma showed that the concentration of ?-endorphin in plasma was not markedly changed after burn except at 2 h after injury, and that of dynorphin A in plasma was reduced markedly after burn injury. The dynamic change of circulating dynorphin A in plasma was coincident with that of immune function. Our results suggest that burn-induced immunosuppression may be related to decrease of circulating dynorphin A levels.

T-cell exhaustion is characterized by the stepwise and progressive loss of T cell functions under conditions of antigen-persistence, which occurs following chronic infections and tumor outgrowth. Exhausted T cells present functional defects, express multiple inhibitory receptors and show reprogrammed transcriptional regulation. As T cell exhaustion is correlated to its dysfunction to control infections and tumors, exploring new strategies to target exhausted T cell may reverse this dysfunctional state and reinvigorate immune response. This study takes CD8+ T cell as an example, which acts as an important subset involved in exhaustion state, discuss current understanding of the properties of exhausted T cell and the mechanisms that promote and maintain this state, and reveal new therapeutic targets for chronic infection and cancer.

Objective To explore the association of NH2-terminal pro-B-type natriuretic peptide ( NT-proBNP) with the risk of type 2 diabetes.Methods One hundred and twenty-six impaired glucose regulation( IGR) participants from Diabetic Identification Center of Tianjin Metabolic Diseases Hospital were included.NT-proBNP was measured in plasma samples collected from participants at baseline condition.Results At baseline, NT-proBNP was inversely associated with body mass index, waist circumference, fasting glucose, insulin and low-density lipoprotein-cholesterol( LDL-C) levels.During a follow-up of 2 years, 51 participants reported a new diagnosis of diabetes from OGTT.Baseline quartiles of NT-proBNP were inversely associated with diabetes risk, even after multivariable adjustment.Theadjustedrelativerisksfordiabeteswere1.0(reference),0.83(95%CI0.74-0.96),0.78(95%CI 0.68-0.90), 0.74 (95%CI 0.64-0.87) for the 1st, 2nd, 3rd, and 4th quartiles of baseline NT-proBNP, respectively ( P<0.01 ) .Conclus ion In IGRpopulation , lowlevels of NT-proBNP were associated with a significantly increased risk of type 2 diabetes.

Objective:To investigate the effects and mechanisms of curcumin on insulin resistance in streptozocin-induced diabetic rats.Methods:Diabetic rats were induced by intraperitoneal injection of STZ, then all the rats were randomly divided into diabetes (DM), diabetes+ curcumin (DM+ Cur), and diabetes + buffer control (DM+ NC) groups. Normal SD rats were used as control group (NC). The DM+ Cur group was treated with curcumin, while the DM+ NC group was treated with equal-volume buffer. The test lasted 12 weeks. The blood glucose was detected, and hyperinsulinemic-euglycemic clamp test was performed to estimate peripheral insulin resistance. At the end of the experiments, rats were killed and the total protein and cell membrane protein were extracted from skeletal muscle. The levels of phosphorylated PI3K, phosphorylated AKT, total PI3K, and total AKT were measured by Western blot. The levels of total GLUT4 and GLUT4 of cell membrane were also detected by Western blot, GLUT4 levels in skeletal muscle cell membranes were detected by immunofluorescence.Results:Blood glucose levels of DM+ Cur group were lower than those of DM group [(18.67±1.99 vs 24.38±2.88) mmol/L, P<0.05], and insulin resistance was also improved[the average GIR(14.69±0.29 vs 10.25±0.30) mg·kg -1·min -1, P<0.01]. The phosphorylation levels of PI3K and AKT were increased, and GLUT4 translocation to the cell membrane was increased. Conclusion:By activating the PI3K/AKT pathway, curcumin promotes GLUT4 translocation, increases skeletal muscle glucose uptake, and finally improves insulin resistance.

Objective To discuss the clinical application of percutaneous radiologic gastrostomy (PRG) in treating dysphagia associated with amyotrophic lateral sclerosis (ALS),and to evaluate its safety and improvement effect on patient's nutritional status in ALS patients with pulmonary insufficiency.Methods The clinical data of 51 ALS patients who received PRG were retrospectively analyzed.The success rate of surgery and postoperative complications were recorded.All patients were regularly followed up,and the longterm complications as well as the one-,3-and 6-month mortality rates after the surgery were documented.The improvement of patient's nutritional status was evaluated.Results PRG was successfully accomplished in all 51 patients,the technical success rate was 100％.Mild postoperative complications occurred in 7 patients (13.73％) and severe massive hemorrhage in one patient (2.0％).After PRG,no signs or symptoms of impaired respiratory function were observed.No death occurred in one month and in 3 months after PRG.Six months after PRG,three patients died(6.8 ％,3/44).One month after PRG,31 patients had an increase in body weight of more than 1 kg,and the mean BMI was increased from preoperative t8.60±2.14 to postoperative 19.27±1.81 (one month after PRG),19.17±1.93 (3 month after PRG) and 18.89±2.33 (6 month after PRG).Conclusion For the performance of PRG no gastroscopy or anesthesia is needed,thus,the risk of aspiration asphyxia can be reduced in ALS patients complicated by pulmonary insufficiency and the success rate as well as the safety can be improved.Therefore,this technique is an effective means to ensure that the ALS patients with pulmonary insufficiency can get adequate energy intake to improve their nutritional status.