Objective To study the effect and possible mechanism of diazoxide on myocardial ischemia/reperfusion (I/R) injury in diabetic rats, and the influence of insulin intervention which aims to maintain blood sugar levels within the normal range on the protective function of cardiomyocytes. Methods 126 health male Sprague-Dawley (SD) rats were intraperitoneally injected with one dose of 60 mg/kg streptozotocin (STZ) to reproduce diabetic model. The diabetic rats were randomly divided into seven groups, with 18 rats in each group. Myocardial I/R model was established by 30 minutes ligation of the left anterior descending branch of the coronary artery, and 120 minutes blood circulation recover. Sham group was only threaded without ligation. Rats in I/R group, diazoxide group (DZ group), and Ottawa vine penicillin (WNT) group were infused intravenously with 2 mL of 0.1% dimethyl sulphoxide (DMSO), DZ (7 mg/kg), and WNT (15 μg/kg), respectively, after 25 minutes of ischemia. Sham group was only injected with 2 mL of 0.1% DMSO. DZ+WNT group was infused with WNT 5 minutes before the injection of DZ. Insulin intervention (RI) group received a continuous insulin infusion to maintain the blood sugar at the level of 4-6 mmol/L. RI+DZ group was infused with DZ after ischemia for 25 minutes based on blood sugar control. Hemodynamic parameters in each group were monitored continuously. The pathological changes of myocardium were observed with hematoxylin and eosin (HE) staining. The expressions of phosphorylated protein kinase B (p-Akt) and phosphorylated glycogen synthase kinase-3β (p-GSK-3β) were determined by Western Blot. Results Compared with sham group, the cardiac functions of the intervention groups were significantly decreased, and severe myocardial injury was observed. Compared with I/R group, the cardiac functions of intervention groups were not obviously improved. However, after insulin intervention by which blood sugar was maintained within normal range, the cardiac function and myocardial injury were further aggravated. Compared with sham group (the expression value of sham group was set as 1), the expressions of p-Akt in other groups including I/R group, DZ group, RI group, and RI+DZ group showed no statistically significant difference (gray value: 1.07±0.09, 1.03±0.07, 1.07±0.07, 1.02±0.08 vs. 1.00, all P > 0.05). However, the expressions of p-Akt were decreased in WNT group and DZ+WNT group as compared with those of sham group and I/R group (gray value: 0.54±0.06, 0.51±0.05 vs. 1.00 and 1.07±0.09, all P < 0.05). The expressions of p-GSK-3βshowed no statistically significant difference in I/R group, DZ group, WNT group, and DZ+WNT group as compared with sham group (gray value: 0.97±0.08, 1.00±0.11, 0.98±0.06, 0.97±0.09 vs. 1.00, all P > 0.05). However, the expression of pGSK-3β was increased in RI group, RI+DZ group as compared with sham group and I/R group (gray value: 1.68±0.08, 1.70±0.05 vs. 1.00 and 0.97±0.08, all P < 0.05), and it was significantly higher in RI+DZ group than that of DZ group (gray value: 1.70±0.05 vs. 1.00±0.11, P < 0.05). Conclusions Diazoxide after myocardial injury could not protect the myocardium from I/R injury in diabetic rats, and did not trigger the activation of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Insulin intervention by which blood sugar was maintaine d within the normal range exacerbates myocardial I/R injury in diabetic rats.

Objective To study the risk factors of MRI for the prediction of collapse in patients with avascular necrosis of the femoral head.Methods Twenty-two patients (39 hips) diagnosed avascular necrosis of femoral head by MR were enrolled in our study.The following MR appearances were evaluated:bone marrow edema,joint fluids,signal intensity and location of the lesion.The volume and surface area of the necrosis zone were calculated.The time of follow-up was 18-84 months (median,25 months).Logistic regression analysis was used to predict the risk factors by SPSS 13.0.The maximum value of Youden index was selected as the critical point to predict the collapse of femoral head and to define the sensitivity,specificity and accuracy.Results In the 39 hips with femoral head necrosis,21 hips had collapse.Bilateral collapse occurred in 5 cases.In 25 hips with the necrosis surface larger than 25％,collapse occurred in 21 (84％); In 8 hips with the volume of femoral head necrosis larger than 30％,collapse occurred in all cases; 1n 33 hips with the necrosis locating at the superolateral quadrant,collapse occurred in 21 (63.6％); In 22 hips with necrotic areas showing heterogeneous signal intensity,collapse occurred in 18(81.8％) ;In 25 hips with large amount of joint effusion,collapse occurred in 16 (64％) ;in 18 hips with bone marrow edema,collapse occurred in 13 (65％).Joint fluid,heterogeneous signal intensity and lesions in the superolateral quadrant,volume ratio,and area ratio were the high risk factors,while bone marrow edema was a relatively low risk factor.The area under ROC curves for area ratio of NASA was greater than that for volume ratio (0.987 vs 0.902).When the critical value for area ratio was 26.7％,the true positive rate was 95.2％,true negative rate was 94.4％,and Youden's index was 0.896.Conclusions The collapse of necrosis of femoral head may result from many factors.The femoral head was easy to collapse when it had large enough area of necrosis and mixed signal intensity,a large amount of joint effusion,bone marrow edema,and superolateral quadrant location.The critical value for area ratio to predict the collapse of femoral head was about 26.7％.The area ratio is more accurate than volume ratio in predicting the collapse of necrosis of femoral head.

The innate immune system plays a crucial role in the rapid recognition and elimination of invading microbes. Detection of microbes relies on germ-line encoded pattern recognition receptors (PRRs) that recognize essential bacterial molecules, so-called pathogen-associated molecular patterns (PAMPs). A subset of PRRs, belonging to the nucleotide binding oligomerization domain (NOD)-like receptor (NLR) families, detects viral and bacterial pathogens in the cytosol of host cells and induces the assembly of a multi-protein signaling platform called the inflammasome. The inflammasome serves as an activation platform for the cysteine protease Caspase-1, a central mediator of innate immunity. Caspase-1 initiates a novel form of cell death called pyroptosis. Inflammasome activation by pathogen-associated signatures results in the autocatalytic cleavage of Caspase-1 and ultimately leads to the processing and thus secretion of pro-inflammatory cytokines, most importantly interleukin (IL)-1β and IL-18. Here, we review the recent advancements of negative regulatory functions and mechanisms leading to the activation of NLRP1, NLRP3, NLRC4, and AIM2 inflammasomes.
Apoptosis ; Carrier Proteins ; Caspase 1 ; Humans ; Immunity, Innate ; Inflammasomes ; metabolism ; Inflammation ; metabolism ; Interleukin-18 ; metabolism ; Interleukin-1beta ; metabolism ; Nod Signaling Adaptor Proteins ; metabolism ; Signal Transduction

ObjectiveTo analyze the surveillance results at the national surveillance spots of brucellosis from 2006 to 2010,to know the epidemic status of national brucellosis,and to provide scientific evidences for evaluating of surveillance quality and formulating of surveillance strategies and measures.Methods The brucellosis surveillance data collected from the Surveillance Reports of Major Infectious Diseases and Vector-Biological Monitoring Report in China from 2006 to 2010,and the National Diseases Surveillance Information Management System were classified and analyzed using two stage clustering statistical analysis.Results According to national routine surveillance,the incidence of brucellosis increased from 1.55 per 100 000 in 2006 to 2.62 per 100 000 in 2010.Reported brucellosis cases were mainly in Inner Mongolia,Shanxi,Heilongjiang and other regions,and reported time was from March to August,which accounting for 79.87％(114 265/143 064).The brucellosis cases were mainly youth,male,farmers and herdsman.In the national surveillance spots of the brucellosis,217 648 cases received epidemic survey,of which 61 905 cases received serological test,the positive rate was 19.66％(12 169/61 905),and 10 318 new cases were found; the highest positive rate of serological test was 41.19％(2757/6694) which was found in Zhalantun of Inner Mongolia; the detection rate of pathogen culture was 2.49％(29/1165); the positive rates of serological test in cattle and sheep were 1.07％(2355/219 352) and 0.93％ (2766/296 176),respectively.The surveillance spots were classified into four grades according to cluster analysis.Conclusions The epidemic continues to rise in human surveillance spots of brucellosis.Although national surveillance spots play an important role in the surveillance of brucellosis,the quality and quantity of surveillance work of national brucellosis surveillance spots should be improved,different management measures should be taken in different surveillance spots according to classified results of the cluster analysis.This study provides some basis to improve the utilization of health resources and the level of Brucella disease prevention and control work.

OBJECTIVETo investigate the role of Xuebijing injection(XBJI, traditional Chinese medicine), in inhibiting TLR4--NF-kappaB--IL-1beta pathway of myocardial hypoxia/reoxygenation in rats.

METHODSThirty six male SD rats (280 +/- 30) g were randomly divided into six groups (n = 6): normal group (N group), balanced perfusion group (BP group), model group (M group), low dose XBJI group (XBJI(L) group), middle dose XBJI group (XBJI(M) group), high dose XBJI group (XBJI(H) group). By Langendorff isolated heart perfusion device to establish the model of myocardial hypoxia/reoxygenation in rats. ELISA was used to detect the concentration of interleukin-1beta (IL-1beta); Western blot was used to detect the expression of nuclear factor kappa B p65 (NF-kappaB p65) protein and toll like receptor 4 (TLR4) protein; and RT-PCR to determine the expression of NF-kappaB p65 mRNA and TLR4 mRNA;To observe microstructure changes of hypoxia/reoxygenation myocardial by light microscopy.

RESULTSCompared with M group, the IL-1beta concentration, NF-kappaB p65 and TLR4 protein,NF-kappaB p65 and TLR4 mRNA of XBJIL group, XBJI(M) group, XBJI(H) group expression decreased in varying degrees,and decreased most obviously all in XBJI(M) group (P < 0.05, P < 0.01); Myocardical structural damage was serious in M group, and improved after treatment XBJI, the most obvious was the XBJI(M).

CONCLUSIONDifferent dose of XBJI can inhibit TLR4--NF-kappaB--IL-1beta signal transduction pathway and reduce several inflammatory reaction after myocardial hypoxia/reoxygenation injury, the 4 ml/100 ml of XBJI is the best.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Heart ; drug effects ; Inflammation ; Interleukin-1beta ; metabolism ; Male ; Myocardium ; pathology ; RNA, Messenger ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; Signal Transduction ; Toll-Like Receptor 4 ; metabolism ; Transcription Factor RelA ; metabolism

BACKGROUNDLeptin is a protein mainly secreted by adipocytes, and the major function of leptin was its role in body weight regulation. It is suggested that increased levels of circulating leptin may contribute to anorexia in pathologic conditions including chronic obstructive pulmonary disease (COPD). Recent studies have provided evidence for a link between leptin and proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha). This study aimed to explore the role of serum leptin in the malnutrition of COPD patients, and to observe the changes of serum leptin levels during acute exacerbation, also to investigate relationship between leptin and TNF-alpha.

METHODSSeventy-two COPD patients and 34 control subjects participated in this study. Seventy-two COPD patients were divided into 3 groups: group COPD IA (patients without malnutrition during acute exacerbation, n = 25), group COPD IB (patients without malnutrition during stable disease, n = 29), group COPD II (patients with malnutrition during stable disease, n = 18). To eliminate the effect of sex differences, all patients and controls were male. Body mass index (BMI), percent ideal body weight (IBW%), triceps skin-fold thickness (TSF), mid-upper arm circumference (MAC), mid-upper arm muscle circumference (MAMC), serum leptin and TNF-alpha levels, serum prealbumin (PA), serum transferrin (TF), serum albumin (Alb), total lymphocytes count (TLC), forced expiratory volume in one second (FEV(1)), maximal inspiration pressure (MIP) and maximal expiration pressure (MEP) were measured in all participants. Leptin levels were measured by radioimmunoassay. TNF-alpha levels were measured by ELISA. The between group difference and correlation of these parameters were analyzed.

RESULTSSerum leptin levels were significantly lower in group COPD II [(4.07 +/- 3.42) ng/ml] than in group COPD IB [(9.72 +/- 6.67) ng/ml] and controls [(8.21 +/- 5.41) ng/ml] (P < 0.05). There was no statistically significant difference in serum leptin levels between group COPD IA [(10.82 +/- 6.40) ng/ml], group COPD IB [(9.72 +/- 6.67) ng/ml] and controls [(8.21 +/- 5.41) ng/ml]. There was no statistically significant difference in serum TNF-alpha levels between group COPD II [(8.03 +/- 3.37) pg/ml], group COPD IA [(8.90 +/- 1.60) pg/ml], and group COPD IB [(7.25 +/- 2.08) pg/ml]. There was no significant correlation between leptin and TNF-alpha in any group.

CONCLUSIONSLeptin was not involved in anorexia and weight loss of COPD patients. There was no statistically significant difference in serum leptin levels between COPD patients during stable stage and acute exacerbation, and there was no significant correlation between TNF-alpha and leptin during the regulation of the energy balance in COPD patients.

Adult ; Aged ; Anorexia ; etiology ; Humans ; Leptin ; blood ; Male ; Malnutrition ; blood ; etiology ; Middle Aged ; Pulmonary Disease, Chronic Obstructive ; blood ; complications ; Tumor Necrosis Factor-alpha ; analysis ; Weight Loss

Purpose: To investigate the relationship between rumination, coping strategies, and subjective well-being (SWB) and test the mediating effects of coping strategies on rumination and SWB in patients with breast cancer (BC). Methods: This cross-sectional study assessed rumination, coping strategies, and SWB using the General Well-being Schedule, the Chinese Event-Related Rumination Inventory, and the Medical Coping Modes Questionnaire in BC patients admitted to a tertiary general hospital in China. Results: SWB was positively associated with the total score for rumination (r = .32, p < .01), deliberate rumination (r = .75, p < .01), and confrontation (r = .58, p < .01). The relationship between rumination and SWB was mediated by confrontation (indirect effect = .74). Conclusion BC diagnosis can affect patient's SWB. These findings indicate that rumination and confrontation have direct and indirect effects on SWB. Therefore, psychological interventions focused on improving coping may increase SWB. Notwithstanding, larger longitudinal studies are needed to further examine the relationship between cognitive processes, coping strategies, and SWB.

Purpose: To investigate the relationship between rumination, coping strategies, and subjective well-being (SWB) and test the mediating effects of coping strategies on rumination and SWB in patients with breast cancer (BC). Methods: This cross-sectional study assessed rumination, coping strategies, and SWB using the General Well-being Schedule, the Chinese Event-Related Rumination Inventory, and the Medical Coping Modes Questionnaire in BC patients admitted to a tertiary general hospital in China. Results: SWB was positively associated with the total score for rumination (r = .32, p < .01), deliberate rumination (r = .75, p < .01), and confrontation (r = .58, p < .01). The relationship between rumination and SWB was mediated by confrontation (indirect effect = .74). Conclusion BC diagnosis can affect patient's SWB. These findings indicate that rumination and confrontation have direct and indirect effects on SWB. Therefore, psychological interventions focused on improving coping may increase SWB. Notwithstanding, larger longitudinal studies are needed to further examine the relationship between cognitive processes, coping strategies, and SWB.

OBJECTIVETo explore the role of toll-like receptor 2 (TLR2) and toll-like receptor 4 (TLR4) in myocardial ischemia/reperfusion injury (MI/RI) by observing the dynamic expression changes at mRNA and protein levels early after myocardial ischemia/reperfusion (I/ R).

METHODSThe Wistar rats were randomly divided into Sham and I/R group (n = 42), and killed according to different reperfusion time (1, 2, 4, 6, 12, 24 h and 7 d). Structural and morphous changes of myocytes were observed under optical microscope. The mRNA and protein levels of TLR2 and TLR4 were detected using real-time PCR (RT-PCR). Monocyte chemokine protein-1 (MCP-1) and interleukine-6 (IL-6) mRNA levels were measured by reverse transcriptase-polymerase chain reaction (rt-PCR).

RESULTS(1) With the extension of reperfusion time, the myocardial infarct size increased smoothly, and reached the plateau at 4 h, then stayed in the platform. After reperfusion for 7 d, the ventricular had been remodeled. (2) At the beginning of reperfusion, myocardial structure showed no significant change in Sham group, but had different degrees of injury in I/R group. In rats of the group reperfused for 7 d the left ventricular remodeling could be visible. (3) Compared to sham group,TIR2, TLR4, MCP-1, IL-6 mRNA level were increased in myocardium in I/R group. TLR2 and TLR4 both peaked at 4 h of reperfusion, IL6 peaked at 6 h, followed by a gradually decrease. TLR4 and IL-6 mRNA levels rose again at 7 d. MCP-1 level in I/R group remained fairly with sham group at the beginning of reperfusion, and markedly elevated at 7 d.

CONCLUSIONExpression of TLRs mRNA in myocardium during early after myocardial ischemia/reperfusion increased rapidly and activated TLRs might play an important role in MI/RI through promoting the generation of inflammatory factors. At the late reperfusion, TLRs levels raise again and the expression of inflammatory factors increase once again, Those may probably affect the remodeling of ventricular, and injure myocardial structure and function.

Animals ; Chemokine CCL2 ; metabolism ; Disease Models, Animal ; Interleukin-6 ; metabolism ; Male ; Myocardial Reperfusion Injury ; metabolism ; Rats ; Rats, Wistar ; Toll-Like Receptor 2 ; metabolism ; Toll-Like Receptor 4 ; metabolism

OBJECTIVETo investigate the effects of ischemic postconditioning (IPostC) on pneumocyte apoptosis after lung ischemia/reperfusion injury in rats.

METHODSAdult male SD rats were randomly divided into 3 groups based upon the intervention (n = 8): control group (C), lung ischemic reperfusion group (LIR), LIR+ IPostC group (IPostC). At the end of the experiment, blood specimens drawn from the arteria carotis were tested for the content of malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and myeloperoxidase (MPO); the pneumocyte apoptosis index (AI) was achieved by tennrminal deoxynucleotidyl transferase mediated dUTP nick end abeling (TUNEL); the expression of Bcl-2, Bax protein in lung tissue was accessed by quantitative immunohistochemistry (MHC) and Bcl-2, Bax mRNA by RT-PCR.

RESULTSIPostC could significantly attenuate the MDA level, MPO activity and improve SOD activity in blood serum which was comparable to I/R and significantly reduced the number of TUNEL-positive cells compared with I/R group, expressed as Al (% total nuclei) from (39.0 +/- 3.46) to (8.0 +/- 0.88) (P < 0.01). The protein and mRNA expression of Bcl-2 and Bax showed that IPO significantly attenuated the ischemia/reperfusion-upregulated expression of Bax protein but improved the expression of Bcl-2 that improved the Bcl-2/Bax ratio (P < 0.01) .

CONCLUSIONIPostC may attenuate pneumocyte apoptosis in LIRI by up-regulating expression of Bcl-2/Bax ratio and by inhibiting oxidant generation and neutrophils filtration.

Alveolar Epithelial Cells ; cytology ; Animals ; Apoptosis ; Ischemic Postconditioning ; Lung ; metabolism ; pathology ; Lung Injury ; physiopathology ; Male ; Malondialdehyde ; metabolism ; Peroxidase ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; physiopathology ; Superoxide Dismutase ; metabolism ; bcl-2-Associated X Protein ; metabolism