Objective:To establish a method for the determination of 4-methyl-N-(4-(pyridin-3-yl) pyrimidin-2-yl) benzene-1,3-diamine as an impurity in the preparation of imatinib mesylate. Methods: An LC-MS/MS method was used with ESI ion source con-trolled by a positive-ion mode. The MRM mode was performed with 278. 1/106. 1 as the scanning and ion-pair. Acetonitrile solution containing ammonium formate and formic acid was used with gradient elution. Results:The linear range was 1. 572~47. 160 ng/ml(r=0. 999 7). The detection limit was 0. 002 1ng and the limit of quantitation was 0. 006 8ng. The average recovery was 100. 9% with RSD of 2. 88. The results of specificity, solution stability, repeatability and durability all met the specification. Conclusion:The meth-od is sensitive, accurate and special in the determination of 4-methyl-N-(4-(pyridin-3-yl) pyrimidin-2-yl) benzene-1,3-diamine in imatinib mesylate.

Objective To evaluate the effects of edaravone postconditioning and remote ischemic postconditioning on myocardial ischemia/reperfusion (I/R) injury in rats.Methods Forty male Sprague-Dawley rats,aged 8 weeks,weighing 250-300 g,were randomly divided into 5 groups (n =8 each):sham operation group (group S); group I/R; edaravone postconditioning group (group E); remote ischemic postconditioning group (group P); edaravone postconditioning and remote ischemic postconditioning group (group EP).Myocardial I/R was induced by occlusion of anterior desending branch of left coronary artery for 30 min followed by 180 min reperfusion.Edaravone 3 mg/kg was injected intravenously at 1 min before reperfusion in groups E and EP.The animals underwent 10 min ischemia of bilateral hind limbs starting from 20 min of myocardial ischemia in groups P and EP.Left ventricular systolic pressure (LVSP),left ventricular end-diastolic pressure (LVEDP) and ± dp/dtmax were measured and recorded during reperfusion.Results Compared with group S,LVSP and ± dp/dtmax were significantly decreased and LVEDP was increased in the other groups (P ＜ 0.05).LVSP and ± dp/dtmax were significantly higher and LVEDP was lower during reperfusion in groups E,P and EP than in group I/R,and in group EP than in groups E and P (P ＜ 0.05).Conclusion Edaravone postconditioning and remote ischemic postconditioning can alleviate myocardial I/R injury and offers better efficacy than either alone.

Objective To evaluate the effect of remote limb ischemic postconditioning on the level of adiponectin during myocardial ischemia-reperfusion (I/R) in rats.Methods Fifty-seven male Sprague-Dawley rats,aged 8 weeks,weighing 250-350 g,were randomly divided into 3 groups (n =19 each):sham operation group (group S); group I/R; remote limb ischemic postconditioning group (group RLIP).Myocardial ischemia was induced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 180 min reperfusion in urethane-anesthetized rats.In group S,the anterior descending branch was only exposed but not ligated.The animals underwent 10 min ischemia of bilateral hind limbs starting from 20 min of occlusion of the anterior descending branch,followed by reperfusion in RLIP group.The changes in S-T segment were recorded at 30,60,120 and 180 min of reperfusion.At 180 min of reperfusion,the blood samples were taken from the jugular vein for determination of serum levels of creatine kinase MB (CK-MB) and cardiac troponin Ⅰ (cTnⅠ).The animals were then sacrificed and hearts were removed for measurement of myocardial infarct size (IS) and adiponectin contents in myocardial tissues (by ELISA).Results Compared with group S,S-T segment was significantly elevated at each time point,myocardial IS,and serum cTnⅠ and CK-MB levels were increased,and adiponectin contents were decreased in I/R and RLIP groups.Compared with group I/R,elevation of S-T segment was significantly decreased at each time point,myocardial IS,and serum cTnⅠ and CK-MB levels were decreased,and adiponectin contents were increased in RLIP group.Conclusion The mechanism by which remote limb ischemic postconditioning reduces myocardial I/R injury is related to increased level of adiponectin in the myocardium of rats.

Objective:To evaluate the tolerance and safety of Zhengbiguanjie tablets in healthy volunteers to provide the safe dose range for phase II clinical trial. Methods:Totally 36 healthy volunteers were randomly divided into five single dose groups at different doses ranging from 400 mg to 3200 mg per day and two multiple dose groups with 1600 mg and 2400 mg for continuous 7 days. The tol-erance and safety of the tablets were observed. Results: All vital signs were normal in all the volunteers in both single and multiple dose tests. Although some indicators turned into abnormal after the administration, it was not significant for clinical judgment. Neither drug combination nor serious adverse reactions were shown during the trial. However, two mild adverse events occurred and disap-peared later without any treatment. Conclusion:All the volunteers have good tolerance to Zhengbiguanjie tablets. The study proved the safety of Zhengbiguanjie tablets at single and multiple dose.

Objective Study the management and outcomes of one-stage repair of aortic coarctation or interrupted aortic arch associated with cardiac anomalies through median sternotomy.Methods From July 2002 to June 2009,43 patients with aortic coarctation(34 cases)or interrupted aortic arch(9 cases)and associated with cardiac anomalies underwent one-stage repair.There were 27 males and 16 females.The age ranged from 5 months to 9 years and the body weight from 3.5 kg to 29.0 kg.The associated cardiac anomalies included ventricular septal defect in 42 patients,patent ductus arterious in 34,secundum atrial septal defect in 12,subaortic stenesis in 5,mitral valve regurgitation in 2 and double outlet of right vantricule in 1.All patients underwent one-stage repair through median sternotomy.The aortic continuity was reestablished by direct anastomosis between the descending aortic segment and aortic arch.Results There was one postoperative death.The causs was pulmonary hypertension and severe low cardiac output syndrome.The postoperative complications included severe low cardiac output syndrome in 3 patients,hypoxemia in 6,pneumonia in 11,atelectasis in 14,injury of recurrent laryngeal nerve in 19,and supra ventricular tachycardia in 23.34 patients were followed up from 3 months to 5 years and were in good condition without recoarctation.Conclusion The outcomes of early and medium term for one-stage repair of aortic coarctation or interrupted aortic arch and associated cardiac anomalies through median sternotomy is excellent.Technique of extended anastomosis between the descending aortic segment and aortic arch may reduce the incidence of recoarctation

Objective To evaluate the role of autophagy in hydrogen-induced inhibition of apoptosis in hippocampal neurons in a rat model of orthotopic liver transplantation (OLT).Methods Fifty-six pathogen-free healthy adult male Sprague-Dawley rats,aged 8-10 weeks,weighing 220-250 g,were used in the study.Thirty-two rats were selected and assigned into 4 groups (n =8 each) using a random number table:sham operation group (group S),OLT group,hydrogen-rich saline group (group HS) and chloroquine group (group CQ).The other 24 rats severed as the donors.In group S,laparotomy was performed,and the related blood vessels were isolated.The model of OLT was established in OLT,HS and CQ groups.In group OLT,normal saline 6 ml/kg was slowly injected via the inferior vena cava at 5 min before anhepatic phase.In group HS,hydrogen-rich saline 6 ml/kg was slowly injected via the inferior vena cava at 5 min before anhepatic phase.In group CQ,autophagy inhibitor chloroquine 60 mg/kg was injected intraperitoneally at 1 h before establishment of the model,and the other treatments were similar to those previously described in group HS.At 6 h of reperfusion,the rats were sacrificed and hippocampi were isolated for determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity,for pathological examination (with light microscope),and for detection of cell apoptosis (by TUNEL staining) and expression of autophagy-and apoptosis-related proteins caspase-3,cytochrome c (Cyt c),microtubule-associated protein 1 light chain 3 Ⅱ (LC3 Ⅱ),Beclin-1 and p53 in hippocampal tissues (by Western blot analysis).Apoptosis index (AI) was calculated.Results Compared with group S,the MDA content and AI were significantly increased,the SOD activity was decreased,and the expression of caspase-3,Cyt c,LC3 Ⅱ,Beclin-1 and p53 was up-regulated in OLT,HS and CQ groups (P＜0.05).Compared with group OLT,the MDA content and AI were significantly decreased,the SOD activity was increased,the expression of caspase-3 and Cyt c was down-regulated,and the expression of LC3 Ⅱ,Beclin-1 and p53 was up-regulated in group HS (P＜0.05).Compared with group HS,the MDA content and AI were significantly increased,the SOD activity was decreased,and the expression of caspase-3 and Cyt c was up-regulated,and the expression of LC3 Ⅱ,Beclin-1 and p53 was down-regulated in group CQ (P＜0.05).Conclusion The mechanism by which hydrogen inhibits apoptosis in hippocampal neurons is related to promotion of autophagy in a rat model of OLT.

OBJECTIVESTo assess the changes of the levels of plasma endothelin (ET-1), nitric oxide (NO) and atrial natriuretic peptide (ANP) after cardiopulmonary bypass (CPB) and the influence of inhaled nitric oxide in patients with ventricular septal defect (VSD) and pulmonary hypertension (PH).

METHODSSixty patients with VSD were enrolled in this study. They were divided into 2 groups: group A [no-PH group, mean pulmonary artery pressure (mPAP) < 20 mm Hg (1 mm Hg = 0.133 kPa) n = 20] and group B (PH group, mPAP > 20 mm Hg, n = 40). Group B was subdivided into two groups by randomized block, group B(1) (inhaled NO group, n = 20) and group B(2) (contrast group, n = 20). The plasma ET-1, NO, ANP concentrations were assayed at 24 h pre-operation and 0 h, 1 h, 5 h, 12 h, 24 h, 48 h after CPB.

RESULTSThe preoperative plasma ET-1, NO and ANP concentrations in group B were significantly higher than those in group A. In three groups, the plasma ET-1 concentration at 0 h after CPB was significantly higher than that at 24 h pre-operation, and the plasma NO concentration at 0 h after CPB was significantly lower than that at 24 h pre-operation. In group B, the plasma ANP concentration at 0 h after CPB was significantly higher than that at 24 h pre-operation. After CPB, the plasma ET-1 concentration in group B(1) decreased faster than that in group B(2), and the plasma NO concentration in group B(1) increased faster than that in group B(2). In group B, the preoperative plasma ET-1 concentration negatively correlated with the preoperative plasma NO concentration and positively correlated with the preoperative ANP concentration.

CONCLUSIONSThe broken dynamic balance of ET-1/NO may take part in generation and development of pulmonary hypertension. ANP acts as a favorable physiological regulating factor in the pathogenesis of pulmonary hypertension. CPB can regulate the level of ET-1 up and NO and ANP down while inhaled NO can cause the level of ET-1 down and the level of NO up.

Administration, Inhalation ; Atrial Natriuretic Factor ; blood ; Cardiopulmonary Bypass ; Child, Preschool ; Endothelin-1 ; blood ; Female ; Heart Septal Defects ; blood ; surgery ; Humans ; Hypertension, Pulmonary ; blood ; surgery ; Male ; Nitric Oxide ; blood ; pharmacology

Objective:To evaluate the role of nuclear factor erythroid 2-related factor 2 (Nrf2)/nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) signaling pathway in propofol postconditioning-induced reduction of hippocampal neuron injury in a rat model of oxygen-glucose deprivation and restoration (OGD/R).Methods:The hippocampal neurons were isolated from fetal rats of Wistar rats at 16-18 days of gestation and primarily cultured for 7 days and then divided into 4 groups ( n=42 each) using a random number table method: control group (group C), OGD/R group (group O), propofol post-conditioning group (group P) and Nrf2 siRNA(-) transfection group (group N). The cells were routinely cultured in group C. The cells were subjected to oxygen-glucose deprivation for 1 h followed by oxygen and glucose supply in group O. Propofol (final concentration 1.2 μg/ml) was added immediately after oxygen and glucose supply, the cells were then cultured for 2 h, and the culture medium was replaced with the normal culture medium in group P. The primarily cultured neurons were transfected with Nrf2 gene knockout lentivirus on 3rd day of culture, 24 h later the cells were then routinely cultured, and the model was prepared and propofol conditioning was performed on 7th day. Cells were collected at 24 h of incubation for determination of the cell apoptosis (by flow cytometry), expression of Nrf2 and NLRP3 mRNA and protein (using quantitative real-time polymerase chain reaction or Western blot), concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and IL-1β, and activities of glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) (kit method). Results:Compared with group C, the apoptosis rate of neurons was significantly increased, concentrations of TNF-α, IL-6 and IL-1β were increased, the levels of GSH, SOD and CAT were decreased, the expression of Nrf2 and NLRP3 protein and mRNA was up-regulated, and the nuclear/plasma ratio of Nrf2 was increased in O and P groups ( P<0.05). Compared with group O, the apoptosis rate of neurons was significantly decreased, the concentrations of TNF-α, IL-6 and IL-1 β were decreased, the levels of GSH, SOD and CAT were increased, the expression of Nrf2 protein and mRNA was up-regulated, the nuclear/plasma ratio of Nrf2 was increased, and the expression of NLRP3 protein and mRNA was down-regulated in group P ( P<0.05). Compared with group P, the apoptosis rate of neurons was significantly increased, concentrations of TNF-α, IL-6 and IL-1β were increased, the levels of GSH, SOD and CAT were decreased, the expression of Nrf2 protein and mRNA was down-regulated, the nuclear/plasma ratio of Nrf2 was decreased, and the expression of NLRP3 protein and mRNA was up-regulated in group N ( P<0.05). Conclusions:Nrf2/NLRP3 signaling pathway is involved in propofol postconditioning-induced reduction of hippocampal neuron injury in a rat model of OGD/R.

The review summarizes the risk factors, diagnostic criteria and perioperative control strategies of acute kidney injury in pediatric liver transplantation, aiming to provide rationales for proper managements.

Petroleum hydrocarbon pollutants are difficult to be degraded, and bioremediation has received increasing attention for remediating the hydrocarbon polluted area. This review started by introducing the interphase adaptation and transport process of hydrocarbon by microbes. Subsequently, the advances made in the identification of hydrocarbon-degrading strains and genes as well as elucidation of metabolic pathways and underpinning mechanisms in the biodegradation of typical petroleum hydrocarbon pollutants were summarized. The capability of wild-type hydrocarbon degrading bacteria can be enhanced through genetic engineering and metabolic engineering. With the rapid development of synthetic biology, the bioremediation of hydrocarbon polluted area can be further improved by engineering the metabolic pathways of hydrocarbon-degrading microbes, or through design and construction of synthetic microbial consortia.
Bacteria/genetics* ; Biodegradation, Environmental ; Hydrocarbons ; Petroleum ; Petroleum Pollution/analysis* ; Soil Microbiology ; Soil Pollutants