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Objective:Principal Investigator (PI) system is the most common model of scientific research organization and management in colleges and universities. PI is the head of the laboratory or the leader of the research team who has the authority to manage the supporting team, funds, and space (laboratory). We aim to explore the advantages and problems of the PI system implementation and deeply understand how to effectively and scientifically manage the project management, personnel coordination, and fund use of the entire team to promote the scientific research output of the PI platform of medical schools in China.Methods:By concluding and analyzing the management experience and main bottlenecks of PI laboratories at home and abroad, and summarizing our center's experience in assisting the management of PI laboratories in life sciences, we explored a new model of PI system development suitable for China.Results:Under PI system, the person in charge systematically learns to operate his or her laboratory scientifically. Perfection and improvement of the methodologies of team formation, laboratory public affairs management, and laboratory fund management can effectively avoid existing problems and follow the intrinsic laws of scientific research development and truth-seeking, promote the development in discipline development, interdisciplinary cooperation, personnel training, and study style construction.Conclusions:As the leader and manager of the scientific research team, PI is critical to the development of scientific research in universities in China. The incubation of a new scientific management model for the PI team is conducive to promoting the scientific and technological innovation of the PI team and the long-term development of scientific research institutions.
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OBJECTIVE: To investigate the role of high mobility group protein 1(HMGB1) in toluene diisocyanate(TDI) induced nucleotide-binding oligomerization domain like receptor family pyrin domain-containing 3(NLRP3) inflammasome activation in human bronchial epithelial cells(HBECs). METHODS: i) The TDI-human serum albumin(HSA) stimulation experiment: the HBECs in logarithmic growth phase were randomly divided into control group, low-, medium-and high-dose groups that were pretreated with TDI-HSA with the final concentration of 0.00, 40.00, 80.00 and 120.00 mg/L for 12 hours. ii) The HMGB1 expression inhibition experiment: the HBECs in logarithmic growth phase were divided into control group, TDI-HSA group, TDI-HAS+negative-siRNA group, and TDI-HAS+HMGB1-siRNA group. The cells in TDI-HAS+negative-siRNA group and TDI-HAS+HMGB1-siRNA group were infected with HBECs with negative-siRNA lentivirus and HMGB1-siRNA lentivirus, respectively. Cells in these two groups and the TDI-HSA group were treated with 120.00 mg/L of TDI-HSA for 12 hours. The cells in the control group were not treated with TDI-HAS. iii) The expression of HMGB1, NLRP3, apoptosis-associated speck-like protein containing CARD(ASC), pro-caspase-1 and caspase-1 p20 proteins in all groups were detected by Western blot. The number of NLRP3 and caspase-1 inflammasome in TDI-HSA stimulation experiment was observed by immunofluorescence method. RESULTS: i) TDI-HSA stimulation experiment: the relative protein expression of HMGB1 and ASC was higher in HBECs of medium-and high-dose groups than that of control group(all P values were <0.01). The relative protein expression of NLRP3 and casepase-1 p20 and the number of NLRP3-caspase-1 inflammasome were higher in HBECs of 3 dose groups than that of control group(all P values were <0.01). The number of NLRP3-caspase-1 inflammasome in HBECs increased obviously in low-, medium-and high-dose groups as compared to the control group(all P values were <0.05). The number of NLRP3-caspase-1 inflammasome in HBECs increased with the increase of TDI-HSA dose(all P values were <0.01). ii) The HMGB1 expression inhibition experiment: the relative protein expression of HMGB1, NLRP3, ASC, pro caspase-1 and caspase-1 p20 in HBECs were higher in the TDI-HSA group and TDI-HSA + negative-siRNA group than those of the control group(all P values were <0.01). The above indexes of HBECs were lower in the TDI-HAS + HMGB1-siRNA group than those in the TDI-HSA group and TDI-HSA + negative-siRNA group(all P values were <0.01).CONCLUSION: TDI treatment in HBECS can induce the increase of HMGB1 protein expression and activate NLPR3 inflammasome. Inhibition of HMGB1 expression can down-regulate the expression of NLPR3 and its related proteins.
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Acute ischemic stroke (AIS), as the third leading cause of death worldwide, is characterized by its high incidence, mortality rate, high incurred disability rate, and frequent reoccurrence. The neuroprotective effects of Ginkgo biloba extract (GBE) against several cerebral diseases have been reported in previous studies, but the underlying mechanisms of action are still unclear. Using a novel in vitro rat cortical capillary endothelial cell-astrocyte-neuron network model, we investigated the neuroprotective effects of GBE and one of its important constituents, Ginkgolide B (GB), against oxygen-glucose deprivation/reoxygenation and glucose (OGD/R) injury. In this model, rat cortical capillary endothelial cells, astrocytes, and neurons were cocultured so that they could be synchronously observed in the same system. Pretreatment with GBE or GB increased the neuron cell viability, ameliorated cell injury, and inhibited the cell apoptotic rate through Bax and Bcl-2 expression regulation after OGD/R injury. Furthermore, GBE or GB pretreatment enhanced the transendothelial electrical resistance of capillary endothelial monolayers, reduced the endothelial permeability coefficients for sodium fluorescein (Na-F), and increased the expression levels of tight junction proteins, namely, ZO-1 and occludin, in endothelial cells. Results demonstrated the preventive effects of GBE on neuronal cell death and enhancement of the function of brain capillary endothelial monolayers after OGD/R injury in vitro; thus, GBE could be used as an effective neuroprotective agent for AIS/reperfusion, with GB as one of its significant constituents.
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Animals , Rats , Apoptosis , Brain Ischemia , Drug Therapy , Cell Survival , Cells, Cultured , Disease Models, Animal , Endothelial Cells , Ginkgolides , Pharmacology , Glucose , Lactones , Pharmacology , Neurons , Neuroprotective Agents , Pharmacology , Oxygen , Plant Extracts , Pharmacology , Stroke , Drug TherapyABSTRACT
Objective To investigate the influence of iodixanol-320 and iopromide-370 on the heart rate of patients in coronary dual-source CT angiography (CTA).Methods The data of 389 patients underwent coronary CTA examinations were retrospectively collected and received contrast media (CM) with either iodixanol-320 (group A) or iopromide-370 (group B), randomly.The heart rate before CM injection (predose HR), during injection (postdose HR) were both recorded.As for the preclinical protocol, patients with heart rate less than 75 beats per minute were pretreated with nitrates (n=278),0.25 mg.Mean heart rate changes from pre to postdose HR were assessed.Results The patients whose mean heart rate changes from pre to postdose were larger than 10 beats per minute was 8(4.4%) for group A and 10(4.8%) for group B.No statistically differences were observed between them(P>0.05).With only intravenous injections of two contrast agents, the patients' heart rates decreased in both groups (4.2 vs 2.7 beats per minute,P>0.05), while the effect could be reduced by nitrates.Conclusion There is no difference in the heart rate between the 2 agents after intravenous injection of either iodixanol-320 or iopromide-370 in coronary CTA with approximately 4% patients whose mean heart rate changes from preto postdose were larger than 10 beats per minute in each group.
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Objective To review the experiences of 31 cases of totally thoracoscopic cardiac surgery of cardiopulmonary bypass in children with congenital heart disease.Methods Thirty one children with congenital heart disease received totally thoracoscopic cardiac surgery procedures during the period from October 2012 to May 2016.The ages of these children were ranged from 2 years and 7 months old to 6 years old with average value (4.6 ± 1.4)years old.The body weights were ranged from 12 ～ 24 kg with average value (17 ± 3.5) kg.Among 31 children,there were 12 cases of atrial septal defect,and 19 cases of ventricular septal defect.Through three-hole shape incision at the right chest wall,each hole was 1.5 to 2.0 cm long,and operation field were revealed totally by thoracoscope.Cardiopulmonary bypass was built through femoral arteriovenous intubation.Results Thirty one children were all cured.None of them suffered severe complications such as renal failure,respiratory failure,low cardiac output syndrome,atrioventricular block,and residual shunt.Duration of cardiopulmonary bypass was 62 ～ 185 (126.4 ± 45.2) min,and duration of myocardial ischemia was 18 ～ 118 (53.4 ± 31.2)min.Duration of Postoperative mechanical ventilation was 2 ～ 7 (5.3 ±-1.5) h.Duration of intensive care unit (ICU) stay was 15 ～ 21 (19 ± 1.3) h.Drainage volume of 24 hours after operation was 0～ 130(57 ± 36.2)ml.Volume of red blood cell transfusion was 0 ～ 2 (1.2 ± 0.8) U.Postoperative hospital stay was 4 ～ 7 (6.2 ± 1.2) d.Conclusions For children with congenital heart disease as simple atrial septal defect or ventricular septal defect,thoracoscopic surgical repair can be achieved the same therapeutic results as traditional median sternotomy surgery while having advantages such as smaller incision,less bleeding and none sternal maluniorts.
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Objective To explore the significance in judging the different clinical stages of relapsing polychondritis (RP) patients through examining the changes of aggrecanase and metabolic fragments of aggrecan.MethodsIn comparison with the control group (20 cases),40 patients were divided into the stable stage group (22 cases) and the active stage group (18 cases).The aggrecanase-generated neoeptitopes in cartilage matrix were analysed by immunohistochemistry and Western blot(WB) respectively.The mRNA and protein levels of aggrecanase-1,2 expressed in cartilage cells were measured by real-time reverse transcriptional polymerase chain reaction(RT-PCR) and WB respectively.The difference of these results among these three groups was analyzed accordingly.ResultsThe expression of aggrecanase-1,2 in mRNA level was measured by real-time RT-PCR.The values of aggrecanase-1,2 mRNA 2 -ΔΔC1 were 1.00 ± 0.26 and 1.00 ± 0.27 in control group,1.47 ± 0.11 and 1.57 ± 0.13 in stable stage group,2.09 ±0.12 and 2.09 ± 0.19 in active stage group respectively.By one-way ANOVA analysis,the difference between every two groups was statistically significant (F was 299.113 and 459.013,P ＜ 0.01 ).In comparison with control group,aggrecanase-1,2 increased significantly in both stable and active stage group (P ＜ 0.01 ) and aggrecanase-1,2 increased more significantly in active stage group than in stable stage group (P ＜ 0.01 ).The results from WB analysis indicated that aggrecanase-1,2 could not be detected in control group,and they were detectable in stable stage group and increased in active stage group at the relative molecular of 68 000 Da or 73 000 Da respectively.The aggrecanase-generated neoeptitopes were analyzed by WB as well.The results indicated that NITEGE and ARGSV could be detected in stable stage group and increased in active stage group at the relative molecular of 70 000 Da or 48 000 Da respectively,but there were no signals in control group.Similar with the previous WB results,no signals of NITEGE or ARGSV eptitopes were detected in normal cartilage matrix ( no red staining) by use of immunohistochemical staining.However,in stable stage group and active stage group,these eptitopes were apparently detected (obviously red staining).ConclusionWith the progression of the RP,the activity of the aggrecanase is enhanced,and the degradation of the aggrecan is increased,associated with the severity of the disease.
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Objective To evaluate the effects of ulinastatin on cardiac function in heart valve replacement patients with cardio-pulmonary bypass (CPB).Methods 120 patients received valve replacements were divided into 4 groups at random.Group U 1,preconditioning group:ulinastatin parenteral solution (20 000 U/kg) was injected into the central veins for 10 min before the ascending aorta was clamped.Group U2,postconditioning group:ulinastatin ( 10 000 U/kg) was injected into the aortic root for 5 min before the aortic clamp was opened.Group U3,combined the treatments of group U1 and group U2.Group C was served as control without using ulinastatin.The ST-T of ECG at different 8 time points was recorded from preanesthesia to the end of operation.The dosage of vasoactive agents in the 4 groups was recorded after the aortic clamp was opened.Blood samples were taken from the radial artery at 4 time points during 1O min before the ascending aorta was clamed to the end of operation for determining the serum concentration of H-FABP,IMA,CK-MB,MDA and SOD.The changes in myocardium were examined by microscope.Results The automatic reheating rate of heart in group U1,group U2,and group U3 were 70％,73％ and 90％ respectively,which were all higher than group C (33％) after the aortic clamp was opened in 3 -5 min.The scores of reperfusion arrhythmia,change of ST segments in ECG ( elevation or depression),the dosage of vasoactive drugs ( dopamine and adrenaline) and their using time,the concentration of MDA,H-FABP,IMA and CK-MB in group U1 and group U2 were ＜ than those of group C ( P ＜0.05 ),but was ＞ than those of group U3 ( P ＜0.05 ).The activity of SOD in group U1 and group U2 were ＞ than those of group C ( P ＜ 0.05 ),but was ＜ than those of group U3 ( P ＜ 0.05 ).There were no significant differences between group U1 and group U2( P ＞0.05 ).The myocardium in group C had focal coagulative necrosis.The damage of myocardium in group U3 was minor,the cytoplasm and nucleus was homogeneous,and the boundaries were distinct.Conclusion Ulinastatin parenteral solution preconditioning and postconditioning could improve heart function after valves replacement on CPB.The protective effects were not significantly different regarding ulinastati was administered into the central veins before the ascending aorta was clamped vs.it was injected into the aortic root before the aortic clamp opening.Combined these 2 administration methods and dosages could produce collaborative protection.
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ObjectiveTo investigate the effects of ulinastatin postconditioning and combining ulinastatin postconditioning with pretreatment on myocardial inflammatory response in patients undergoing cardiac valve replacement under CPB.MethodsEighty NYHA class Ⅱ or Ⅲ patients of both sexes aged 21-59 yr undergoing cardiac valve replacement under CPB were randomly divided into 4 groups ( n =20 each): group control (group C) ; group ulinastatin pretreatment ( group U1 ) ; group ulinastatin postconditioning (group U2 ) and group ulinastatin pretreatment and postconditioning combined (group U3 ).Ulinastatin 20 000 U/kg was infused via central vein at 500-1000 U·kg-1 ·min-1 after tracheal intubation until 10 min before cross-clamping of ascending aorta in groups U1 and U3.Ulinastatin 10 000 U/kg was infused into root of aorta at 4000-5000 U· kg- 1 · min- 1 at 5-7 min before declamping of aorta in groups U2 and U3.Blood samples were obtained from radial artery before cross clamping of ascending aorta,at 40 min after aortic cross-clamping,at 45 min after declamping of aorta (T3) and at the end of operation for polymorphonuclear leukocyte (PMN) count,routine analysis of blood and determination of plasma concentrations of IL-10,TNF-α,IL-1 and IL-6 (by ELISA).Myocardial specimens were obtained at 45 min after declamping of aorta for determination of IL-1β and IL-6 expression by immune-histochemistry.Results Ulinastatin pretreatment and/or postconditioning significantly increased plasma IL-10 concentration and decreased plasma IL-1,IL-6,TNF-α concentrations and PMN count and myocardial IL-1β and IL-6 expression in groups U1,U2 and U3 as compared with group C.Plasma IL-10 concentration was significantly higher and plasma IL-1,IL-6 and TNF-α concentrations,PMN count and myocardial IL-1β and IL-6 expression were lower in group U3 than in groups U1 and U2.ConclusionUlinastatin postconditioning can inhibit myocardial imflammatory response in patients undergoing valve replacement under CPB.The protective effect can be augmented by combining ulinastatin postconditioning with pretreatment.
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Objective To evaluate the effects of ulinastatin postconditioning and combination of ulinastatin preconditioning and postconditioning on myocardial apoptosis in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).Methods Eighty NYHA class Ⅱ or Ⅲ patients of both sexes,aged 21-59,scheduled for cardiac valve replacement with CPB,were randomly divided into 4 groups ( n =20 each):normal saline control group ( group C ),ulinastatin preconditioning group ( group U1 ),ulinastatin postconditioning group (group U2 ) and ulinastatin preconditioning plus postconditioning group(group U3 ).In group U1,uinastatin 20 000U/kg was infused via central vein at 500-1000 U·kg-1 ·min-1 from after tracheal intubation until 10 min before ascending aortic cross-clamping.In group U2,ulinastatin 10 000 U/kg was perfused via aortic root at 4000-5000 U· kg-1 · min-1 at 5-7 min before aortic unclamping.In group U3,ulinastatin preconditioning and postconditioning were performed as described in groups U1 and U2.In group C same volume normal saline was infused instead of ulinastatin.Blood samples were taken from radial artery at 10 min before ascending aortic cross-clamping,40 min after ascending aortic cross-clamping,45 min after aortic unclamping and the end of operation for determination of plasma concentrations of TNF-α and soluble tumor necrosis factor receptor 1 (sTNF-R1).Myocardial tissues were obtained from right atrial appendage at 45 min after aortic unclamping for determination the expression of TNF-d,Bcl-2,Bax and caspase-3 and apoptosis.The Bcl-2/Bax ratio and apoptotic index were calculated.Results Plasma concentrations of TNF-α and sTNF-R1 and the expression of TNF-α,Bax,caspase-3 and apoptotic index were lower,the expression of Bcl-2 and Bcl-2/Bax ratio were higher in groups U1,U2 and U3 thah group C and in group U3 than groups U1,U2 ( P ＜ 0.05 ).Conclusion Ulinastatin postconditioning can inhibit myocardial apoptosis in patients undergoing cardiac valve replacement with CPB,and efficacy of combination of ulinastatin preconditioning and postconditioning is stronger than that of ulinastatin postconditioning.The mechanism is involved in balancing the expression of Bax and Bcl-2 and down-regulating the expression of TNF-α and its receptor.
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Objective The aim of this study was to determine the effect of a new method of cardiac assistant therapy with an extra-aortic balloon pump on the experimental dogs in which myocardial ischemia or infarction were induced, and to ob serve its effectiveness and feasibility. Methods Twelve animal models of myocardia 1 infarction were established with the method of left anterior descending coronary artery ligation. They were divided randomly into two groups, six in the experimental group and six in the untreated group. The end points observed were the differences between the two groups in the blood pressure, cardiac function, myocardial enzymes, infarction size and routine blood variables before procedure, 1,2, 3, 4, 5 and 6 hours after myocardial infarction. Results All six dogs in the experimental group were survived, with a mortality rate of 0.The number of death in the control group was three, with a mortality rate of 50%. Measurements such as mean blood pressure,cardiac output, cardiac index in the experimental group were better than those in the control group ( P ＜ 0.05 ). Mean heart rate before myocardial infarction in the experimental group was 156 beats per minute, as compared with 148 beats per minute in the control group, and was 128 vs. 67 beats per minute respectively six hours after myocardial infarction. The cardiac output was 3.48 vs. 4.98 liters per minute before myocardial infarction and was 6.10 vs. 0.85 liters per minute six hours after myocardial infarction. The average pressure was 94 mm Hg vs. 99 mm Hg before myocardial infarction and was 70 mm Hg vs. 33 mm Hg six hours after myocardial infarction. Conclusion The extra-aortic balloon pump significantly improved the hemodynamic variables of the experimental animals after myocardial infarction and reduced mortality. Injury to the blood cells may be the potential disadvantage.
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Objective To explore the effect of inhaled iloprost (Ventavis) for patients with congenital heart disease associated with pulmonary hypertension.Methods Twenty-two patients with congenital heart disease associated with pulmonary hypertension were selected to inhale Ventsvis by atomizer before surgery ,the required dosage is 25-30ng/(kg.min),aerosolization of iloprest was inhaled by PARI Junior BOY N after diluted with 2ml physiological saline at 3-hour intervals .The change of hemodynamic effects was measured by Doppler ultrasonography after 60min,120min,and 180min.Results The left and fight vemfieular cardiac output at 60min,120min and 180rain after therapy were markedly higher than that before inhaled iloprost ,respirator therapy time was shorter in patients inhaled iloprost.Conclusion inhaled iloprost can increase cardiac output and improve patients cardiac function.Thus,the therapy with inhaled iloprost is effective and feasible.