To establish an HPLC mehod for the analysis of pharmacokinetics of salvianolic acid B in rats. METHODS: The biological samples were extracted with acetic ether. The chromatographic conditions were as follows: Hypersil ODS column (200 mm×4.6 mm, 5μm) was used. The mobile phase was acetonitrile-water(with Ammoniom Acetate 0.25 mol/L) was set at 328 nm. RESULTS: Salvianolic acid B was injected intravenously at doses of 1.6, 3.2, 6.4 mg/kg. The terminal elimination half-life(t1/2) of α phase and β phase was (3.1±0.1) min and (31.5±3.2) min. The extents of excrement,urine and biliary excretion of salvianolic acid B were 1.43%±0.90%, 0.77%±1.01% and 8.82%±4.11%. The tissue concentration of salvianolic acid B was as followed in order: Cheart>Cliver>Clung>Cintestine>Ckidney>Cspleen>Cstomach. The plasma protein binding rate of salvianolic acid B in human plasma and in rat was similar(89.2%±1.8%,92.5%±1.5%). CONCLUSION: The method is accurate, stable and reliable, and can be used for the investigation of salvianolic acid B in pharmacokinetics research. Salvianolic acid B eliminates fast and it shows a high plasma protein binding rate, the mainly excretion way of salvianolic acid B is from biliary.

Objective: To evaluate the long-term prognosis of coronary artery disease (CAD) patients undergoing percutaneous coronary intervention (PCI) by risk stratification with American College of Cardiology (ACC)/American Heart Association (AHA) classification of coronary lesions. Methods: Data used in this study derived from the I-LOVE-IT 2 trial. I-LOVE-IT 2 trial was a prospective, multicenter, randomized, assessor-blinded, noninferiority study. A total of 1 255 patients in I-LOVE-IT 2 trial with only one lesion and underwent biodegradable polymer drug-eluting stent implantation were included and grouped according to ACC/AHA classification of coronary lesions, namely type A/B1 lesion group (n=184), type B2 lesion group (n=457) and type C lesion group (n=614). The primary endpoint was 48-month patient-oriented composite endpoint (PoCE), a composite of all-cause mortality, all myocardial infarction, stroke, and/or any revascularization. The secondary endpoints were target lesion failure (TLF), components of PoCE, major bleeding (bleeding academic research consortium(BARC) type 3-5) and definite/probable stent thrombosis within 48 months. The incidences of endpoint events were compared in the three groups. The multivariable Cox hazard ratio model was used to analyze the independent predictors of PoCE and TLF at 48 months. Results: Incidences of PoCE at 48 months were significantly higher in patients with type C lesion compared with patients with type A/B1 (24.43%(150/614) vs. 14.13%(26/184), P<0.05) or B2 lesion (24.43%(150/614) vs. 15.97%(73/457), P<0.05). The multivariable Cox hazard ratio model showed that the type C lesion were the independent predictors of 48-month PoCE (HR=1.59, 95%CI 1.21-2.08, P<0.001) and TLF (HR=2.31, 95%CI 1.53-3.49, P<0.001). After multivariable adjustment, the HRs of PoCE for patients with type C lesion versus type A/B1 and type B2 were 1.91 (95%CI 1.25-2.92, P=0.003) and 1.64 (95%CI 1.23-2.20, P<0.001), respectively. Meanwhile, the HRs of TLF for patients with type C lesion versus type A/B1 and type B2 were 2.45 (95%CI 1.29-4.64, P=0.006) and 2.55 (95%CI 1.62-4.02, P=0.001), respectively. Conclusions The ACC/AHA classification of coronary lesions has good discrimination with long-term outcomes for CAD patients undergoing PCI. The type C lesion is associated with a worse prognosis, enough attention should be paid in these patients during routine clinical management.

Objective To evaluate the effect of sevoflurane on the electrophysiological stability of ventricular myocardium in diabetic rats.Methods Thirty-two pathogen-free healthy adult male Sprague-Dawley rats,aged 3 months,weighing 180-220 g,were divided into 4 groups (n=8 each) using a random number table:control group (group C),sevoflurane group (group S),diabetes mellitus group (group D) and diabetes mellitus plus sevoflurane group (group D+S).After the model of diabetes mellitus was established,the hearts were rapidly excised and perfused in a Langendorff apparatus with oxygenated (95％ O2-5％ CO2) K-H solution.After 15 min stabilization,the hearts were continuously perfused for 30 min with K-H solution in C and D groups and with K-H solution saturated with 2.5％ sevoflurane in S and D+S groups.At 15 min of stabilization (T0) and 15 and 30 min of perfusion (T1-2),heart rate (HR) and monophasic action potential (MAP) duration at 50％ and 90％ repolarization (MAPD50,MAPD90) in the two layers (endocardium,epicardium) of the anterior left ventricular wall were recorded.Transmural dispersion of repolarization (TDR) was calculated.S1S2 program-controlled stimulation was performed at the end of perfusion,and the occurrence of effective refractory period (ERP) and ventricular arrhythmia (VA) was recorded.ERP/MAPD90 was calculated.Results Compared with group C,HR was significantly decreased at T1-2 in group S,HR was significantly decreased and MAPD50 and MAPD90 in epicardium and endocardium were prolonged at T0-2 in D and D + S groups,TDR was significantly enlarged at T0and ERP/MAPD90 was decreased in group D,and the incidence of arrhythmia and induction rate of VA were significantly increased in D and D+S groups (P＜0.05).Compared with group D,TDR was significantly decreased at T2,the incidence of arrhythmia and induction rate of VA were decreased,and ERP/MAPD90 was enlarged in group D+S (P＜0.05).Conclusion Sevoflurane can enhance electrophysiological stability of ventricular myocardium in diabetic rats and decrease the risk of ventricular arrhythmia.

Objective:To evaluate the effect of selective inhibitor of caspase-1 VX-765 on cognitive function in a rat model of hemorrhage shock and resuscitation (HSR).Methods:Forty-eight clean-grade healthy male Sprague-Dawley rats, aged 9-10 weeks, weighing 350-400 g, were divided into 4 groups ( n=12 each) using a random number table method: sham operation group (S group), HSR group (H group), VX-765 group (V group), and solvent control group (C group). The rats in H, V and C groups were subjected to hemorrhage by bleeding from femoral vein to achieve mean arterial pressure of 25-35 mmHg which was maintained at this level for 60 min followed by resuscitation with shed blood within 15 min to restore blood pressure, and normal saline was infused when needed.VX-765 1 mg/kg and 0.4% polyethylene glycol 1 mg/kg were intravenously injected via the femoral vein immediately after the end of resuscitation in V and C groups, respectively.Six rats in each group were selected and sacrificed at 12 h after the end of resuscitation, and the cerebral cortex was removed for determination of neuronal pyroptosis (by immunofluorescence) and degree of cortical edema (using T2-weighted imaging). Cognitive function was measured by open field test on day 7 after resuscitation in the rest 6 rats in each group. Results:Compared with S group, the pyroptosis rate in cortical neurons at 12 h after resuscitation and degree of cortical edema were significantly increased, the distance in the central square and the number of standing on the back legs were decreased on day 7 after resuscitation, and the time spent in the central square was shortened in H, V and C groups ( P<0.05). Compared with H and C groups, the pyroptosis rate in cortical neurons at 12 h after resuscitation and degree of cortical edema were significantly decreased, the distance in the central square and the number of standing on the back legs were increased on day 7 after resuscitation, and the time spent in the central square was prolonged in V group ( P<0.05). Conclusion:VX-765 can improve the cognitive function, and the mechanism may be associated with inhibiting pyroptosis in cortical neurons in a rat model of HSR.

Objective:To evaluate the effect of exogenous carbon monoxide (CO) on cell apoptosis during acute renal injury induced by hemorrhagic shock and resuscitation (HSR) in rats.Methods:Forty-eight clean-grade healthy male Sprague-Dawley rats, aged 9-10 weeks, weighing 350-400 g, were divided into 4 groups ( n=12 each) by a random number table method: sham operation group (S group), HSR group (H group), HSR plus CORM-3 group (HC group) and HSR plus iCORM-3 group (HiC group). Mean arterial pressure was maintained at 30-35 mmHg for 45 min by withdrawing blood from the femoral vein, and the shed blood was re-transfused within 15 min to reach the initial blood pressure for resuscitation.Normal saline was infused when necessary, and the model of HSR was established.CORM-3 4 mg/kg and iCORM-3 4 mg/kg were added during resuscitation in HC group and HiC group, respectively.Only femoral vein and artery puncture was performed in S group.Blood samples were obtained from the tail vein at 3 h after resuscitation for measurement of serum urea nitrogen (BUN) and creatinine (Scr) concentrations.Rats were sacrificed at 12 h after resuscitation, and renal tissues were obtained for determination of the expression of Bcl-2 and Bak protein and cleaved caspase-3 (by Western blot) and cell apoptosis (by TUNEL). The damage to the renal tubules was assessed by paller assay after HE staining.Bcl-2/Bak ratio and apoptosis rate were calculated. Results:Compared with group S, the serum BUN and Scr concentrations, paller scores, and apoptosis rate were significantly increased, Bcl-2/Bak ratio was decreased, and the expression of cleaved caspase-3 was up-regulated in H, HC and HiC groups ( P<0.05). Compared with group H, the serum BUN and Scr concentrations, paller scores, and apoptosis rate were significantly decreased, Bcl-2/Bak ratio was increased, and the expression of cleaved caspase-3 was down-regulated in group HC ( P<0.05). Compared with group HC, the serum BUN and Scr concentrations, paller scores, and apoptosis rate were significantly increased, Bcl-2/Bak ratio was decreased, and the expression of cleaved caspase-3 was up-regulated in group HiC ( P<0.05). There was no significant difference in the indexes mentioned above between group H and group HiC ( P>0.05). Conclusion:The mechanism by which exogenous CO improves acute kidney injury may be related to inhibiting cell apoptosis in a rat model of HSR.

Objective To study the effects of different concentrations of sevoflurane on monophasic action potentials (MAPs)of three-layer myocardium of ischemia reperfusion in isolated rat hearts.Methods Thirty-two healthy SD male rats,weighing 280-320 g,were randomly divided into four groups after successful preparation of langendorff isolated heart perfusion model and 1 5 min perfusion and balance of K-H fluid.In the ischemia-reperfusion group(group IR),K-H fluid perfusion was stopped and balanced for 15 min and cardiac arrest was induced for 60 min with the injection of Thomas solution (4℃,20 ml/kg)while the heart was protected by the low temperature Thomas so-lution (4℃)around it.Reperfusion of Thomas solution (4℃,10 ml/kg)was performed for 30 min and the heart was resuscitated by the perfusion of K-H fluid for 60 min.In the 0.5 MAC sevoflurane group (group Sev0.5 ),K-H fluid contained 0.5 MAC sevoflurane and other procedures were the same as in group IR.1.0 MAC sevoflurane group (group Sev1.0 ),K-H fluid contained 1.0 MAC sevoflurane and other procedures were the same as in group IR.2.0 MAC sevoflurane group (group Sev2.0),K-H fluid contained 2.0 MAC sevoflurane and other procedures were same as in group IR. HR,MAPs including time course (MAPD50,MAPD90)and MAP amplitude of endocardium,mid-layer myodardium and epicardium was recorded at the time of continuous balance perfusion for 1 5 min (T0),continuous perfusion for 15 min (T1),reperfusion for 15 min (T2)and 30 min (T3). Results Compared with T0and T1,HR was slower at T2and T3(P<0.05);Compared with group IR at T2and T3,HR in group Sev0.5 and group Sev1.0 was higher,that in group Sev2.0 was slower P<0.05);At T2,arrhythmia was observed in 6 rats in group IR,while arrhythmia was observed in 1 rats in group Sev0.5 ,and arrhythmia was observed in 2 rats in group Sev1.0 and arrhythmia was observed in 1 rats in group Sev2.0;Compared with group IR at T3,MAPD50in group Sev0.5 was shorter in three sites(P<0.05);Compared with group IR at T3,MAPD90in other three groups was shorter.Conclusion Different concentrations of sevoflurane can shorten MAPD90of MAPs,and the effects don＇t depend on the concertrations of sevoflurane when it changes from 0.5 MAC to 2.0 MAC;which may be the mechanism of decreased arrhythmias risk caused by sevoflurane.

Objective: To explore the value of SYNTAX revascularization index (SRI) on evaluating the long-term prognosis of coronary artery disease (CAD) patients implanted with biodegradable polymer drug-eluting stents (BP-DES) and define the best threshold of SRI for predicting all-cause mortality in these patients. Methods: Data used in this study derived from the I-LOVE-IT 2 trial (evaluate safety and effectiveness of the Tivoli DES and the Firebird DES for treatment of coronary). I-LOVE-IT 2 trial was a prospective, multicenter, randomized, assessor-blinded, non-inferiority study. A total of 1 829 patients implanted with BP-DES were divided into 3 groups, namely SRI=100% group (n=963), 50%≤SRI<100% group (n=527) and SRI<50% group (n=339). The primary endpoint was 48-month patient-oriented composite endpoint (PoCE), a composite of all-cause mortality, myocardial infarction(MI), stroke, and/or any revascularization. The secondary endpoints were components of PoCE and definite/probable stent thrombosis at 48 months. The receiver operating characteristic curve was used to investigate the best cut-off point of SRI for 48-month all-cause mortality. The Cox regression analysis was used to identify independent predictors of the all-cause death and PoCE at 48 months. Results: Incidence of PoCE at 48 months was significantly lower in SRI=100% group than patients with 50%≤SRI<100%(17.34% (167/963) vs. 22.20% (117/527), P<0.05) and SRI<50% (17.34% (167/963) vs. 24.78% (84/339), P<0.05). Comparing with SRI=100% group, the patients with 50%≤SRI<100% suffered higher rates of all MI (7.78% (41/527) vs. 4.26% (41/963), P<0.05) and target vessel MI (6.45% (34/527) vs. 4.26% (41/963), P<0.05); patients with SRI<50% had higher rates of all-cause mortality (5.90% (20/339) vs. 3.12% (30/963), P<0.05) and any revascularization (14.16% (48/339) vs. 3.12% (30/963), P<0.05). The receiver operating characteristic curve analysis showed that the SRI=65% was the best cut-off point to predict the all-cause mortality at 48 months (area under the curve was 0.58, sensitive was 0.47, specificity was 0.70). Meanwhile, SRI<65% was an independent predictor of 48-month all-cause mortality (HR=2.06, 95%CI 1.25-3.38) and PoCE (HR=1.34, 95%CI 1.09-1.66). Conclusions SRI serves as a good index for predicting long-term prognosis and SRI<65% is an independent predictor of 48-month PoCE and all-cause mortality for CAD patients with BP-DES implantation. Meanwhile, SRI≥65% might be a reasonable threshold of incomplete revascularization.

Objective To explore the distribution of sex, month of onset and type of infection virus in children with hand, foot and mouth disease of different TCM syndromes in Heilongjiang province. Methods A total of 2 688 hospitalized children who met the admission criteria in the Infectious Disease Department of Harbin Infectious Disease Hospital from September 1, 2014 to August 31, 2016 were selected. The TCM syndrome differentiation according to the clinical manifestations of children on the day of admission. The distribution of sex, month of onset and type of infection virus in children with different syndrome types were analyzed by SPSS 19.0 software. Results Hand, foot and mouth disease (HFMD) was more common in males than females in Heilongjiang, with a ratio of 1.58:1. Children of all sexes with hand, foot and mouth disease in Heilongjiang were predominantly with lung-defense syndrome. The incidence of lung-defense syndrome, lung-stomach heat syndrome, damp-heat syndrome and heart-spleen heat syndrome were the majority among the children aged 1-4 years, and the lung-defense syndrome was the highest proportion. From July to September, most of the cases occurred, especially in the case of lung-defense syndrome. Pathogenic tests showed that 1 456 cases were enterovirus universal RNA positive, 203 cases were enterovirus 71 positive and 108 cases were coxsackievirus A16 positive. The most common pathogens of the three pathogens were pathogenic lung-defense syndrome. Conclusions herewere some differences in age, time and virus infection among 2 688 children with hand, foot and mouth disease of different TCM syndromes in Heilongjiang, which may be related to region and climate.

Objective To study the pharmacokinetic status of Cyclophosphamide (CYC) in children with lupus nephritis (LN),as well as the relationship between the pharmacokinetic results and clinical indicators,adverse reactions,curative effect evaluation.Methods Thirty patients hospitalized at Tianjin Children's Hospital from January 2014 to December 2016 were treated with glucocorticoid (GC) combined with CYC.Blood samples were collected in 6 point-in-time after intravenous CYC,a high performance liquid chromatography (HPLC) method was used to detect the blood drug concentration,and the pharmacokinetic results were calculated.All patients were followed up for 24 weeks,and the levels of serum albumin (ALB),24 hours urinary protein,serum creatinine (Scr),complement 3 (C3),therapeutic effect and systemic lupus erythematosus disease activity index scores were evaluated at the same time.Results Pharmacokinetic curve showed the second chamber model,the area under the curve (AUC) of time-effect relationship was (143.55 ±42.43) g/(L · h),peak concentration (Cmax) was (20.02 ± 3.55) g/L,and half-time period (T1/2) was(4.21 ± 0.96) h.Age and gender had no influence on AUC,Cmax and T1/2,and statistically significant correlation was found between serum ALB and T1/2,which was positively correlated (r =0.517,P ＜ 0.05).After 16 weeks of treatment,7 patients were partially responsive,22 cases had a complete remission,and the invalid case was only one.Followed up for 24 weeks,6 patients were partially responsive,24 cases had a complete remission.After 16 weeks of treatment,there were statistical differences in AUC among patients with complete response,partial response or no remission.And after 24 weeks,the patients between complete remission and partial remission had no statistically significant difference in the AUC.After 16 weeks and 24 weeks,T1/2 and Cmax had no statistical differences among those groups of patients.Adverse reactions included leukopenia (3 cases,10.00％),gastrointestinal symptoms (4 cases,13.33％) and respiratory tract infection (6 cases,20.00％).There was no statistical relationship between pharmacokinetic parameters and the occurrence of adverse reactions.Single factor analysis showed that there was a statistical significance between ALB,urine protein quantity and treatment effect,but multi-factor analysis showed that the relation between factors and therapeutic effect had no statistical significance.Conclusions HPLC method can be used for the detection of cyclophosphamide blood drug concentration.The cyclophosphamide pharmacokinetic status of children and adult is similar.ALB and T1/2 show a linear positive correlation.Single factor analysis shows a correlation between ALB and treatment effect.Therefore,the increasing level of plasma propagated before treatment can improve therapeutic effect possibly.Cyclophosphamide pharmacokinetic status has nothing to do with the occurrence of adverse drug reactions in the study.