Objective To investigate the protective effect of a COX inhibitor,flurbiprofen (Flurb) on hepatic ischemia/reperfusion (IR) injury in rats and the action mechanism.Method C57BL/6 mice were randomized into sham,IR and Flurb (4 different doses) groups.The model of segmental (70％) warm hepatic ischemia was established in IR and Flurb groups.Flurbiprofen of different doses (5,7.5,10 and 15 mg/kg) was injected via the tail vein 20 min before ischemia.At different time points after reperfusion,liver cell necrosis and apoptosis were evaluated by HE and TUNEL staining.The COX and inflammatory cytokine gene expression was detected by using realtime PCR.Liver mitochondria were separated and mitochondrial permeability transition (MPT) pore sensitivity was examined by using swelling assay and fluorescence spectrophotometry assay.Result In flurbiprofen groups of different doses,the serum AST and ALT levels were significantly decreased at 6 h after reperfusion as compared with IR group.Moreover,10 mg/kg Flurb pretreatment significantly inhibited the mitochondrial permeability transition (MPT) pore opening,and thus alleviated liver cell damage and prevented mitochondria-related cell death and apoptosis by inhibiting COX-2 and inflammatory factor genes expression such as IL-1β,IL-6 and TNF-α.Conclusion Flurbiprofen protects mice from hepatic I/R injury possibly by inhibiting mitochondrial permeability transition and IL-1β,IL-6 and TNF-α expression,which may provide experimental evidence for clinical use of flurbiprofen to protect liver function in surgical settings other than its conventional use for pain relief.

Background and purpose:Lower expression of E-cadherin is associated with metastasis of cancer cells, however, the correlation between E-cadherin and glucose metabolism has seldom been reported. This article studied the correlation between E-cadherin and glycolysis effect in PANC-1 cells.Methods:Through treatment of transforming growth factor β (TGF-β) in PANC-1 cells to decrease E-cadherin expression, knock-down the gene of E-cadherin interaction protein β-catenin, and overexpressing of E-cadherin, the effects of E-cadherin on the glucose uptake and lactate production ability and on the expression of key glycolytic genes were assessed.Results:E-cadherin negatively regulated the glycolytic effect of PANC-1 cells by inhibiting glucose uptake and lactate production (P<0.05). Moreover, E-cadherin interacting partner β-catenin signiifcantly promoted glucose metabolism transformation in PANC-1 cells (P<0.05). Moreover, key glycolysis regulator sirtuin 3 (SIRT3) could lower E-cadherin expression.Conclusion:Lower expression of E-cadherin induced the transformation of glucose metabolism transformation in PANC-1 cells and manipulation of E-cadherin expression level could change the glycolysis effect. Moreover, through maneuver glycolysis process could inhibit high metastatic potential of pancreatic cancer cells.

Objective To investigate the relationship between ischemic time and thrombus types in patients with ST-segment elevation myocardial infarction (STEMI).Methods Eighty-two STEMI patients undergone emergency percutaneous coronary intervention (PCI) and coronary thrombus aspiration (CTA) from Sep.2012 to Apr.2016 were included and divided into 3 groups according to the ischemic time:≤4 hours (n=36),4-7 hours (n=30) and ＞7 hours (n=16).Visible aspirated thrombi were collected and separated into erythrocyte-rich type,platelet/fibrin-rich type and combined type thrombi by HE dying.The percentage difference of the 3 types thrombi was compared among the 3 groups.Results The percentage of platelet/fibrinrich type,erythrocyte-rich type and combined type thrombi in the 3 groups were as follows:in ≤4h group:61.1％(22/36),8.3％(3/36) and 30.6％(11/36),P=0.019;in 4-7h group:23.3％(7/30),10.0％(3/30) and 66.7％(20/30),P=0.012;and in ＞7h group:43.8％(7/16),12.5％(2/16) and 43.8％(7/16),P=0.913.For platelet/fibrin-rich type thrombi,the percentages in 3 periods were 61.1％(22/36),19.4％(7/36) and 19.4％(7/36),P=0.009;For combined type thrombi,the percentages in 3 periods were 28.9％(11/38),52.6％(20/38) and 18.4％(7/38),P=0.013;For erythrocyte-rich type thrombi,the percentages in 3 periods were 37.5％(3/8),37.5％(3/8) and 25.0％(2/8),P=0.895.Conclusions The types of intracoronary aspirated thrombi differ from various periods.Ischemia time may be an important predicted factor.

Objective To examine the influence of gender difference on the reperfusion delay in patients with ST-elevation myocardial infarction (STEMI).Methods A total of consecutive 325 patients with STEMI were analyzed admitted in the 306 Hospital of PLA from Jan.2011 to Dec.2015.Patients were divided into two groups:male group (n=268) and female group (n=57).The clinical data and the time intervals including symptom onset to first medical contact (So-to-FMC),transfer delay (FMC-to-D),FMC to balloon dilatation (FMC-to-B),activation delay and door to balloon (D-to-B) time were compared between different gender groups,and the prognosis was observed.Results The overall median of pre-hospital delay was 125 minutes.The median of prehospital delay time (male 119.5min vs.female 160.0min) and So-to-FMC time (male 69.5min vs.female 100.0min) were longer in female than in male patients,but no statistical difference existed (P＞0.05) between the two groups in pre-hospital delay,So-to-FMC,FMC-to-B,D-to-B and total ischemia time.Compared with male patients,female patients were more likely to have additional comorbidities,such as hypertension and diabetes mellitus,and lower rate of smoking (P＜0.05).However,the incidence of major adverse cardiac and cerebrovascular events (MACCE) showed no significant difference between female and male patients at 30-day (male 5.22％ vs.female 5.26％) and I-year (male 10.82％ vs.female 8.77％) follow-up (P＞0.05).Conclusion The influence of gender on reperfusion delay is gradually weakening.

Pancreatic ductal adenocarcinoma (PDAC) is among the most devastating human malignancies. The poor clinical outcome in PDAC is partly attributed to a growth-permissive tumor microenvironment. In the PDAC microenvironment, the stroma is characterized by the development of extensive fibrosis, with stromal components outnumbering pancreatic cancer cells. Each of the components within the stroma has a distinct role in conferring chemoresistance to PDAC, and intrinsic chemoresistance has further worsened this pessimistic prognosis. The nucleoside analog gemcitabine (GEM) is usually the recommended first-line chemotherapeutic agent for PDAC patients and is given alone or in combination with other agents. The mechanisms of intrinsic resistance to GEM are an active area of ongoing research. This review highlights the important role the complex structure of stroma in PDAC plays in the intrinsic resistance to GEM and discusses whether antistroma therapy improves the efficacy of GEM. The addition of antistroma therapy combined with GEM is expected to be a novel therapeutic strategy with significant survival benefits for PDAC patients.

Objective: To investigate the impact of symptom onset to first medical contact (SO-to-FMC)time on the prognosis of patients with acute ST-segment elevation myocardial infarction(STEMI). Methods: The clinical data of 341 consecutive STEMI patients, who were hospitalized to our hospital and received primary percutaneous coronary intervention(PCI) from August 2011 to April 2016, were retrospectively analyzed. The patients were divided into ≤90 min group (201 cases) and >90 min group (140 cases) according to the SO-to-FMC time. The treatment time, mortality and incidence of major adverse cardiac and cerebro-vascular events(MACCE) were analyzed. The risk factor of 1-year mortality after PCI and 1-year incidence of MACCE during the post-discharge follow-up period were analyzed by binary logistic regression analysis. The predictor of 4.5-year mortality after PCI was analyzed by multivariate Cox regression analysis. Methods The door to balloon time (104(88, 125) min vs. 111(92, 144)min, P=0.023), first medical contact to balloon time(146(119, 197) min vs. 177(125, 237)min, P=0.005), and symptom onset-to-balloon time(200(170, 257) min vs. 338(270, 474)min, P<0.001)were all significantly shorter in the ≤90 min group than in>90 min group. The 30-day mortality (2.99% (6/201) vs. 7.86%(11/140), P=0.042), 1-year mortality (2.89 (5/173) vs. 9.57(11/115), P=0.015), 1-year incidence of MACCE during the post-discharge follow-up period(1.16%(2/173) vs. 6.96%(8/115), P=0.021), and 4.5-year cumulative mortality(3.00% vs. 11.20%, P=0.007) after PCI were significantly lower in the ≤90 min group than in the >90 min group. Moreover, the 4.5-year incidence with free of MACCE (97.20% vs. 88.80%, P=0.025) during the post-discharge follow-up period was significantly higher in the ≤90 min group than in the >90 min group. In-hospital mortality was similar between the two groups (2.49%(5/201) vs. 6.43%(9/140), P=0.071). Results: The door to balloon time (104(88, 125) min vs. 111(92, 144)min, P=0.023) , first medical contact to balloon time(146(119, 197) min vs. 177(125, 237)min, P=0.005), and symptom onset-to-balloon time(200(170, 257) min vs. 338(270, 474)min, P<0.001) were all significantly shorter in the ≤90 min group than in >90 min group. The 30-day mortality(2.99% (6/201) vs. 7.86%(11/140), P=0.042), 1-year mortality (2.89(5/173) vs. 9.57(11/115), P=0.015), 1-year incidence of MACCE during the post-discharge follow-up period (1.16%(2/173) vs. 6.96%(8/115), P=0.021), and 4.5-year cumulative mortality (3.00% vs. 11.20%, P=0.007) after PCI were significantly lower in the ≤90 min group than in the >90 min group. Moreover, the 4.5-year incidence with free of MACCE (97.20% vs. 88.80%, P=0.025) during the post-discharge follow-up period was significantly higher in the ≤90 min group than in the >90 min group. In-hospital mortality was similar between the two groups (2.49%(5/201) vs. 6.43%(9/140), P=0.071). Results of binary logistic regression analysis showed that the SO-to-FMC time >90 min was the risk factor of 1-year mortality(OR=2.90, 95%CI 1.22-6.92, P=0.016) and 1-year incidence of MACCE (OR=5.19, 95%CI 1.21-22.20, P=0.026) during the post-discharge follow-up period. Multivariate Cox regression analysis demonstrated that the SO-to-FMC time >90 min was the risk factor of 4.5-year mortality after PCI in patients with STEMI (HR=2.88, 95%CI 1.10-7.53, P=0.031). Conclusion Shorting the SO-to-FMC time can significantly reduce the treatment time of STEMI patients, short and long-term mortalities and the incidence of MACCE, and improve the prognosis of patients with STEMI.

Objective:To investigate the influence and mechanism of stromal interaction molecule 1 (STIM1) in microglia/macrophages M1 activation after cerebral ischemia-reperfusion injury.Methods:(1) Animal experiment: 20 male C57BL/6J mice were randomly divided into sham-operated (Sham) group, middle cerebral artery occlusion and reperfusion (MCAO/R) group, MCAO/R+si-Ctrl group, and MCAO/R+si-STIM1 group ( n=5); MCAO/R models were established in mice of the latter 3 groups; empty vector control virus and STIM1 gene knockout lentivirus were transfected into mice in the MCAO/R+si-Ctrl group and MCAO/R+si-STIM1 group. The transfection efficiency of STIM1 and the expression of microglia/macrophages M1 activation marker cluster of differentiation 86 (CD86) in each group were observed. (2) Cell experiment: primary microglia were divided into Ctrl group, oxygen-glucose deprivation/re-oxygenation (OGD/R) group, OGD/R+si-Ctrl group, OGD/R+si-STIM1 group, OGD/R+solvent group, and OGD/R+4-phenylbutyric acid (4-PBA) group; OGD/R models were established in the later 5 groups; empty vector control virus and STIM1 gene knockout lentivirus were transfected into mice in the OGD/R+si-Ctrl group and OGD/R+si-STIM1 group; cells in the OGD/R+4-PBA group were pre-treated with 1 mmol/L 4-PBA for 1 h at 24 h before OGD/R modelling to inhibit endoplasmic reticulum stress (ERS), and cells in the OGD/R+solvent group were pre-treated with 0.5% dimethyl sulfoxide (DMSO) for 1 h at the same time. Reverse transcription quantitative polymerase chain reaction (RT-qPCR), ELISA, Western blotting and other methods were used to detect the levels of CD86, tumour necrosis factor-α ( TNF-α) mRNA, interleukin (IL)-1β, and ERS-related proteins (transcription factor C/EBP homologous protein [CHOP], activated transcription factor 4 [ATF4]) in these cells. Results:(1) Animal experiment: the STIM1 expression in MCAO/R+si-STIM1 group was significantly lower than that in Sham group, MACO/R group and MCAO/R+si-Ctrl group ( P<0.05); as compared with that in the MACO/R group and MCAO/R+si-Ctrl group, the number of microglia/macrophages co-expressing CD86 and Iba-1 around the ischemic foci of mice in the MCAO/R+si-STIM1 group was significantly decreased ( P<0.05). (2) Cell experiment: as compared with those in the OGD/R group and OGD/R+si-Ctrl group, the expression levels of STIM1, CD86, and TNF-α mRNA, and supernatant IL-1β content in the OGD/R+si-STIM1 group were significantly decreased ( P<0.05); as compared with those in the OGD/R group and OGD/R+si-CTRL group, the ATF4 and CHOP expression levels in OGD/R+si-STIM1 group were significantly decreased ( P<0.05); as compared with those in the OGD/R group and OGD/R+solvent group, the CD86 level, TNF-α mRNA expression level and IL-1β content in the OGD/R+4-PBA group were significantly decreased ( P<0.05). Conclusion:STIM1 affects microglia/macrophages M1 activation after ischemia-reperfusion injury by regulating ERS level.

BACKGROUNDPercutaneous coronary intervention (PCI) could develop periprocedural myocardial infarction and inflammatory response and statins can modify inflammatory responses property. The aim of this study was to evaluate whether short-term high-dose atorvastatin therapy can reduce inflammatory response and myocardial ischemic injury elicited by PCI.

METHODSFrom March 2012 to May 2014, one hundred and sixty-five statin-naive patients with unstable angina referred for PCI at Department of Cardiology of the 306th Hospital, were enrolled and randomized to 7-day pretreatment with atorvastatin 80 mg/d as high dose group (HD group, n = 56) or 20 mg/d as normal dose group (ND group, n = 57) or an additional single high loading dose (80 mg) followed 6-day atorvastatin 20 mg/d as loading dose group (LD group, n = 52). Plasma C-reactive protein (CRP) and interleukin-6 (IL-6) levels were determined before intervention and at 5 minutes, 24 hours, 48 hours, 72 hours, and 7 days after intervention. Creatine kinase-myocardial isoenzyme (CK-MB) and cardiac troponin I (cTnI) were measured at baseline and then 24 hours following PCI.

RESULTSPlasma CRP and IL-6 levels increased from baseline after PCI in all groups. CRP reached a maximum at 48 hours and IL-6 level reached a maximum at 24 hours after PCI. Plasma CRP levels at 24 hours after PCI were significantly lower in the HD group ((9.14±3.02) mg/L) than in the LD group ((11.06±3.06) mg/L) and ND group ((12.36±3.08) mg/L, P < 0.01); this effect persisted for 72 hours. IL-6 levels at 24 hours and 48 hours showed a statistically significant decrease in the HD group ((16.19±5.39) ng/L and (14.26±4.12) ng/L, respectively)) than in the LD group ((19.26±6.34) ng/L and (16.03±4.08) ng/L, respectively, both P < 0.05) and ND group ((22.24±6.98) ng/L and (17.24±4.84) ng/L, respectively). IL-6 levels at 72 hours and 7 days showed no statistically significant difference among the study groups. Although PCI caused a significant increase in CK-MB and cTnI at 24 hours after the procedure in all groups, the elevated CK-MB and cTnI values were lower in the HD group ((4.71±4.34) ng/ml and (0.086±0.081) ng/ml, respectively) than in the ND group ((7.24±6.03) ng/ml and (0.138±0.103) ng/ml, respectively, both P < 0.01) and LD group ((6.80±5.53) ng/ml and (0.126±0.101) ng/ml, respectively, both P < 0.01).

CONCLUSIONShort-term high-dose atorvastatin treatment before PCI significantly reduced systemic inflammatory response and myocardial ischemic injury elicited by PCI.

Aged ; Angina, Unstable ; therapy ; Atorvastatin Calcium ; administration & dosage ; therapeutic use ; Female ; Humans ; Male ; Middle Aged ; Myocardial Reperfusion Injury ; drug therapy ; Myocardium ; pathology ; Percutaneous Coronary Intervention ; Systemic Inflammatory Response Syndrome ; drug therapy ; Treatment Outcome

A novel structural dynamics test method and device were designed to test the biomechanical effects of dynamic axial loading on knee cartilage and meniscus. Firstly, the maximum acceleration signal-to-noise ratio of the experimental device was calculated by applying axial dynamic load to the experimental device under unloaded condition with different force hammers. Then the experimental samples were divided into non-specimen group (no specimen loaded), sham specimen group (loaded with polypropylene samples) and bovine knee joint specimen group (loaded with bovine knee joint samples) for testing. The test results show that the experimental device and method can provide stable axial dynamic load, and the experimental results have good repeatability. The final results confirm that the dynamic characteristics of experimental samples can be distinguished effectively by this device. The experimental method proposed in this study provides a new way to further study the biomechanical mechanism of knee joint structural response under axial dynamic load.
Animals ; Cattle ; Biomechanical Phenomena ; Knee Joint/physiology* ; Meniscus ; Mechanical Phenomena ; Weight-Bearing

Dendritic cells (DCs) comprise two functionally distinct subsets: plasmacytoid DCs (pDCs) and myeloid DCs (mDCs). pDCs are specialized in rapid and massive secretion of type I interferon (IFN-I) in response to nucleic acids through Toll like receptor (TLR)-7 or TLR-9. In this report, we characterized a CD56(+) DC population that express typical pDC markers including CD123 and BDCA2 but produce much less IFN-I comparing with pDCs. In addition, CD56(+) DCs cluster together with mDCs but not pDCs by genome-wide transcriptional profiling. Accordingly, CD56(+) DCs functionally resemble mDCs by producing IL-12 upon TLR4 stimulation and priming naïve T cells without prior activation. These data suggest that the CD56(+) DCs represent a novel mDC subset mixed with some pDC features. A CD4(+)CD56(+) hematological malignancy was classified as blastic plasmacytoid dendritic cell neoplasm (BPDCN) due to its expression of characteristic molecules of pDCs. However, we demonstrated that BPDCN is closer to CD56(+) DCs than pDCs by global gene-expression profiling. Thus, we propose that the CD4(+)CD56(+) neoplasm may be a tumor counterpart of CD56(+) mDCs but not pDCs.
Biomarkers ; metabolism ; CD56 Antigen ; genetics ; immunology ; Cell Lineage ; genetics ; immunology ; Dendritic Cells ; immunology ; metabolism ; pathology ; Gene Expression ; Hematologic Neoplasms ; genetics ; immunology ; pathology ; Humans ; Immunophenotyping ; Interferon Type I ; biosynthesis ; metabolism ; Interleukin-12 ; biosynthesis ; metabolism ; Interleukin-3 Receptor alpha Subunit ; genetics ; immunology ; Lectins, C-Type ; genetics ; immunology ; Membrane Glycoproteins ; genetics ; immunology ; Myeloid Cells ; immunology ; metabolism ; pathology ; Receptors, Immunologic ; genetics ; immunology ; Terminology as Topic ; Toll-Like Receptor 4 ; genetics ; immunology ; Toll-Like Receptor 7 ; genetics ; immunology ; Toll-Like Receptor 9 ; genetics ; immunology