BACKGROUNDp38 mitogen-activated protein kinases (MAPK) in ischemic preconditioning (IPC) may be essential to cardioprotection. We assessed whether protective effect of morphine-induced preconditioning (MPC) on myocardial ischemia and reperfusion injury in rat hearts involved p38 MAPK activation.

METHODSMale Spargue-Dawley rats (weighing 300-350 g) were randomly assigned to 1 of the following 8 groups: control (CON, saline vehicle, n=9), SB 203580 (SB, a p38 MAPK inhibitor, n=6), MPC (n=6), IPC (n=9), SB+MPC, SB+IPC, MPC+SB, and IPC+SB (n=6). Infarct sizes (IS), a percentage of the area at risk (AAR), were determined by triphenyltetrazolium (TTC) staining. Tissue samples were processed from the entire AAR of left ventricle for the determination of p38 MAPK protein expression (5 hearts/group). The bands representing the proteins were visualized using an enhanced chemiluminescence detection system.

RESULTSThe IS/AAR was significantly reduced by IPC (12.9+/-1.6)% or MPC (25.3+/-2.9)% compared to the control (52.7+/-5.5)%. SB 203580 administered prior to preconditioning abolished the effect of IPC (SB+IPC: (43.8+/-2.6)%, P>0.05 vs CON, P<0.01 vs IPC), but not MPC (SB+MPC: (30.7+/-0.9)%, P<0.01 vs CON, P>0.05 vs MPC). Treatment with SB 203580 prior to sustained ischemia diminished the protective effect of both MPC (MPC+SB: (42.4+/-2.9)%, P>0.05 vs CON) and IPC (IPC+SB: (52.0+/-2.5)%, P>0.05 vs CON) on IS/AAR. In the IPC group, phospho-p38 MAPK protein increased significantly within 5 minutes into ischemia and remained elevated at 30 minutes into reperfusion, while phospho-p38 MAPK protein in the MPC group only increased significantly at 30 minutes into reperfusion.

CONCLUSIONThe activation of p38 MAPK just acts as a mediator of MPC, whereas it acts as both a trigger and a mediator in IPC.

Animals ; Blotting, Western ; Heart ; drug effects ; Imidazoles ; pharmacology ; Ischemic Preconditioning ; MAP Kinase Signaling System ; Male ; Morphine ; pharmacology ; Myocardium ; enzymology ; Phosphorylation ; Pyridines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; p38 Mitogen-Activated Protein Kinases ; physiology

OBJECTIVETo study the effect of juglone on the ultrastructure of human liver cancer BEL-7402 cells.

METHODSBEL-7402 cells were incubated in the presence of 12.5 micromol/L juglone for 24 h, and fixed in 2.5% glutaraldehyde for HE staining and Coomassie brilliant blue staining and scanning electron microscopy.

RESULTSIncubation with juglone resulted in obvious changes in the cell morphology and cytoskeletal alterations of the cells. Scanning electron microscopy revealed reduced volume of the cell bodies, dissociation of the cells, curling and malformation of the microvilli on the cell surface with rupture of the intercellular junction and enlargement of the intercellular space. The formation of apoptotic bodies was observed. Transmission electron microscopy showed expansion of the endoplasmic reticula, mitochondrial cristea disintegration, nucleolar fragmentation and formation of the apoptotic bodies after the exposure to juglone for 24 h.

CONCLUSIONJuglone can cause ultrastructural changes of human liver cancer BEL-7402 cells and induce their apoptosis.

Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Liver Neoplasms ; ultrastructure ; Naphthoquinones ; pharmacology

OBJECTIVETo compare the responses to sepsis between C57BL/6 and BALB/c mice.

METHODSThirty C57BL/6 mice and 30 BALB/c mice were randomized into sham-operated group and sepsis group (n=15). Sepsis model was established by cecal ligation puncture (CLP) in the mice, and 6 h after the operation, 5 mice from each group were selected randomly for cytokine detection including IL-1beta, IL-2, IL-4, IL-5, IL-10, GM-CSF, IFN-gamma and TNF-alpha by Bio-plex. The other 10 mice in each group were used for survival analysis.

RESULTSThe survival rates of BALB/c and C57BL/6 mice were both 100% in one week after the sham operation, but lowered to 10% and 50% in one week after CLP, respectively. The survival rate of C57BL/6 mice was significantly lower than that of BALB/c mice (P<0.05). After CLP, C57BL/6 mice showed significantly greater IL-4, TNF-alpha and IL-10 production than the sham-operated mice, but the concentrations of the 8 cytokines in BALB/c mice after CLP showed no significant increment.

CONCLUSIONCompared with BALB/c mice, C57BL/6 strain mouse is more sensitive to sepsis.

Animals ; Cytokines ; blood ; Disease Models, Animal ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Random Allocation ; Sepsis ; blood ; Species Specificity

OBJECTIVETo investigate the effect of transfusion of apoptotic and necrotic thymocytes prior to sepsis on the survival rate of mice.

METHODSBALB/c mice are divided into 3 groups and received intravenous injection of PBS (control), apoptotic thymocytes, or necrotic thymocytes. Three days later, cecal ligation and puncture (CLP) were performed to induce sepsis in these mice, and their survival and organ damage were observed.

RESULTSThe survival rates of mice in PBS group was 44.6% at the end of first week after CLP, and obvious lung and kidney damages were observed. A significant increase in the survival rate was found in apoptotic cell transfusion group (69.6%, P=0.012), with also lessened lung and kidney damages. The survival rate of mice in necrotic cell transfusion group was only 31.6% at 2 weeks, significantly lower than that in PBS group (P=0.035), and the lung and kidney damage was even more obvious.

CONCLUSIONTransfusion of apoptotic thymocytes 3 days before induction of sepsis can reduce organ damage and improve the survival rate of mice, while necrotic cell transfusion produces the opposite effect.

Animals ; Apoptosis ; Disease Models, Animal ; Lymphocyte Transfusion ; Mice ; Mice, Inbred BALB C ; Necrosis ; Sepsis ; mortality ; therapy ; Survival Rate ; Thymus Gland ; cytology

Objective To synthesize a novel prostate cancer targeting gene vector PAMAM-PEG-C2min and improve gene transfection efficiency targeting on prostate cancer. Methods The aptamer (C2min) and polyamide-amine (PAMAM) were ligated by polyethylene glycol (PEG). The structure of the synthesized PAMAM-PEG-C2min was identified by NMR. The biological characteristics of the nanoparticles were examined by the uptake experiments and gene transfection experiments (the loaded gene was siR-M) with the prostate cancer cells (PC3 and LNCaP). Besides, the in vivo targeting was investigated using in vivo image system. The in vivo targeting results indicated that PAMAM-PEG-C2min can achieve the simultaneous targeting of two prostate cancer tissues. Results The PAMAM-PEG-C2min synthesis was confirmed by NMR. Cell uptake experiments showed that the cell uptake efficiency of PAMAM-PEG-C2min was concentration dependent. In vitro experiments showed that the PC3 and LNCaP cells transfection efficiency and targeting of PAMAM-PEG modified with C2min were significantly improved compared with the PEG modified PAMAM. Conclusion PAMAM-PEG-C2min is a potential targeted drug delivery vehicle. It provides a new technology platform for comprehensive and specific targeting treatment of prostate cancer.

Objective To investigate the prevalence and associated risk factors of hypertension in Songnan community so as to provide evidence for the early prevention of hypertension.Methods Cluster sampling was employed,and questionnaire survey was performed in 10 185 residents aged above 40 years in Songnan community of Baoshan District.The questionnaires involved with hypertension and associated risk factors.Results The prevalence of hypertension was 49.9% in Songnan community of Baoshan District,and that of men was significantly higher than that of women(53.7% vs 47.3%)(P

Objective To summarize the clinical features of non-classic infantile glycogen storage disease type Ⅱ for early diagnosis.Methods The clinical data including the clinical manifestations and investigation of the 3 nonclassic infantile glycogen storage disease type Ⅱ were retrospectively reviewed from Jun.to Jul.2011.All the 3 cases were diagnosed by measuring acid α-glucosidase (GAA) activity in blood sample.Results All the 3 patients presented development delay,limb muscle weakness without hepatomegaly.Two cases of them presented weakness of respiratory muscle.The serum creatine kinase,aspartate aminotransferase and alanine aminotransferase were high in all the 3 patients.Electromyography studies indicated that one of the patients with susceptible myopathy,one patient with neurogenic damage and one patient with mixed damage of the neuromascular.Echographic evidence of hypertrophic cardiomyopathy was detected in 2 patients.GAA activity of the 3 patients in blood sample had diagnostic value.Conclusions Nonclassic infantile glycogen storage disease type Ⅱ is easy to be missed due to its non-significant clinical manifestations.The results suggested that GAA activity in blood sample should be screened for the patients with motor development delay,decreased muscle weakness/exercise tolerance and increased of serum creatine kinase.

OBJECTIVETo illustrate the diagnostic value of Th1/Th2 cytokine pattern in childhood hemophagocytic lymphohistiocytosis (HLH) and its diagnostic accuracy.

METHODThe BD(TM) CBA Human Th1/Th2 Cytokine Kit II was used to measure the serum Th1 and Th2 cytokines, including Interferon-gamma (IFN-γ), tumor necrosis factor (TNF), interleukin (IL)-10, IL-6, IL-4 and IL-2 in 50 patients with de novo HLH admitted to our hospital from Oct. 2005 to Aug. 2009. The above cytokine levels were also determined in 250 healthy volunteers and 235 patients with sepsis as controls.

RESULTThe primary features of these patients were prolonged high-grade fever (50/50), hepatomegaly (44/50), splenomegaly (38/50), hemocytopenia (47/50), hyperferritinemia (49/50), coagulopathy (44/50), hemophagocytosis in bone marrow (42/50), liver dysfunction (42/50) and hypertriglyceridemia (42/50). The IFN-γ, TNF, IL-10, IL-6, IL-4 and IL-2 levels for healthy children were (4.6 ± 1.8) ng/L, (4.0 ± 1.2) ng/L, (6.5 ± 1.3) ng/L, (6.0 ± 1.5) ng/L, (2.9 ± 0.8) ng/L and (2.6 ± 0.7) ng/L, while the median levels of them in acute phase of HLH children were 1138.5 (49.2 - 5000.0) ng/L, 3.4 (1.0 - 25.1) ng/L, 740.5 (26.5 - 5000.0) ng/L, 66.1 (3.9 - 4472.6) ng/L, 3.9 (1.0-32.8) ng/L and 4.0 (1.0 - 51.1) ng/L, respectively. The cytokine levels decreased to 9.1 (1.9 - 180.1) ng/L, 2.9 (1.0 - 11.0) ng/L, 11.4 (2.9 - 184.2) ng/L, 6.5 (1.0 - 44.8) ng/L, 2.7 (1.0 - 6.5) ng/L and 4.1 (1.0 - 12.0) ng/L respectively after remission. The IFN-γ, IL-10 and IL-6 levels in acute phase were significantly higher than those after remission and those of the healthy control (P all < 0.001). IL-4, IL-2 and TNF slightly elevated or at normal range in acute phase of HLH. The patients with sepsis showed a different cytokine pattern, with an extremely high level of IL-6 (median: 251.3 ng/L, range: 8.4- > 5000.0 ng/L) and moderately elevated level of IL-10 (median: 46.5 ng/L, range: 3.1 - 5000.0 ng/L), whereas IFN-γ was only slightly elevated (median: 9.2 ng/L, range: 1.3 - 498.8 ng/L). When the criteria for HLH set as the following: IFN-γ > 100 ng/L, IL-10 > 60 ng/L and the concentration of IFN-γ higher than that of IL-6, the specificity reached as high as 98.7% and the sensitivity was 88.0% for the diagnosis of HLH among patients with HLH and sepsis. Meanwhile, the positive predictive value (PPV) and negative predictive value (NPV) could reach 93.6% and 97.5%, respectively.

CONCLUSIONThe significant increase of IFN-γ and IL-10 with slightly increased level of IL-6 is a sensitive and specific cytokine pattern for childhood HLH, which is helpful for its diagnosis and differential diagnosis.

Adolescent ; Case-Control Studies ; Child ; Child, Preschool ; Cytokines ; blood ; Female ; Humans ; Infant ; Interferon-gamma ; blood ; Interleukin-10 ; blood ; Interleukin-2 ; blood ; Interleukin-4 ; blood ; Interleukin-6 ; blood ; Lymphohistiocytosis, Hemophagocytic ; blood ; diagnosis ; Male ; Sensitivity and Specificity ; Th1 Cells ; metabolism ; Th2 Cells ; metabolism ; Tumor Necrosis Factor-alpha ; blood

Objective Fluid therapy strategy on cardiac surgical patients has always been disputing. The aim of the present study was to observe the effects of goal-directed hemodynamic management strategy on the prognosis of patients undergoing off-pump coronary artery bypass graft. Methods The study was a prospective quality improvement study. Patients who underwent elective off-pump coronary artery bypass grafting in our hospital from January to December 2016 were included in the study, and the implementation of improvement approach was started on June 20, 2016. A total number of 98 patients were included: 56 cases before the improvement (control group) and 42 cases after the improvement (experimental group). The approach of optimizing hemodynamic was standardized vasoactive usage based on the goal-directed fluid therapy taking SVV (Stroke Volume Variation) and CI (Cardiac Index) as the target. Intraoperative and postoperative data were collected through the medical record system. Comparison was done between two groups in the aspects of liquid intake and output, length of postoperative stay in hospital and complications, postoperative awaken time, volume of thoracic drainage in 24h, extubation rate in 6h, time of ICU stay, concentration of Troponin I on the first day after surgery, mortality rate within 30 days and 6 months. Results There was no statistically difference in total fluid intake after the improvement, while the volume of voluven(676.79± 380.90 mL vs 890.48 ±222.58mL,P < 0.05) and urine volume (516.07±224.87 mL vs 695.24± 311.53mL,P < 0.05) increased significantly, the volume of crystal decreased significantly (663.84 ±224.97mL vs 430.24 ±201.76mL,P < 0.001). The positive liquid balance of intake and output volume was significantly reduced (683.82 ±556.08ml vs 456.43 ±505.36ml, P < 0.05). There were no significant differences in proportion of autologous blood or erythrocyte transfusion and volume of blood loss between the two groups (P > 0.05). There were no significant differences between the two groups in postoperative awaken time, volume of thoracic drainage within 24h, extubation rate within 6, concentration of Troponin I on the first day after surgery and ICU stay(P > 0.05). After the improvement, the length of postoperative stay in hospital was reduced compared with the control group (11.81 vs 13.82, P < 0.05). Multiple linear regression analysis was performed after the logarithmic transformation, and the standardized coefficient B of the improvement was -0.296 (SE=0.061, P < 0.05), indicating that the goal-directed hemodynamic management would reduce the length of postoperative stay in hospital by 19.4 %( 95%CI 7.3%~31.5%) with other conditions being equal. Postoperative complications decreased from 41.07% to 16.67 %( P < 0.05). Conclusion The implementation of goal-directed hemodynamic management strategy can reduce postoperative complications, postoperative hospital stay and improve short-term prognosis of patients undergoing off-pump coronary artery bypass surgery.