Aim To investigate the combined pharmacokinetic-pharmacodynamic(PK-PD) model of irbesartan in healthy Chinese male volunteers. Methods Eighteen healthy male volunteers received 300 mg irbesartan tablet orally. The plasma drug concentration (C_p) was determined by HPLC and pharmacologic effects, including SBP, DBP and HR, were measured simultaneously. The pharmakinetic and PK-PD model parameters were calculated. Results The pharmacokinetic profiles were best fitted a two-compartment open model. There was a hysteresis loop between effects and plasma concentrations. The relationship between effects and effect compartment concentrations of drugs could be represented by the Sigmoid-E_ max model. Conclusion We successfully eatablished the PK-PD model of irbesartan in healthy male volunteers. These findings may provide a more rational basis for patient-specific dosage individualization.

OBJECTIVE:To optimize the extraction craft of gentiopicrin from gentian.METHODS:The extraction craft was optimized by orthogonal test with gentiopicrin as an index,and the content of gentiopicroside was determined by TLC scanning method.RESTLUTS:The quantity of menstruum and the extraction times of gentiopicrin had significant influence in the gentiopicrin extraction(P

OBJECTIVE: To optimize the extraction conditions of plumula nelumbinis. METHODS: The semi - bionic extraction (SBE) conditions were optimized by homogeneous design while total alkaloids and dry extract were adopted as markers. Factors of extraction time, solute quantity and the pH values were evaluated for their effects on extraction process. RESULTS: Optimal parameters were as follows: plumula nelumbinis was extracted in water 8 times as much as it for 3 times; the pH values of the water for the 1st, 2nd and 3rd decoctions were 5.0,6.0 and 8.0, respectively; the boiling lasted 4 hours. CONCLUSION: The method prouides theoretical reference for the extraction plumula nelumbinis.

Objective To explore the efficacy and safety of bedside continuous blood purification (CBP) in the treatment of neonatal multiple organ failure (MOF).Methods Totally 6 newborn infants of MOF were hospitalized in department of neonatology in our hospital from June 2011 to June 2013.These 6 cases of clinical data were retrospectively analyzed,6 neonates were treated with CBP combined with conventional treatment.The model for CBP was continuous veno-venous hemodialysis filtration (CVVHDF),blood flow velocity was 3 to 5 ml/(kg· min),replacement fluid dose was 20 to 30 ml/(kg· h),dialysis fluid dose was 15 to 25 rnl/(min· m2).The clinical outcome measures included,blood pressure,blood pH,K+,Na+,blood urea nitrogen,creatinine,urine volume,PaO2/FiO2 and epinephrine intravenous dose,respectively before CBP treatment,6 h,12 h,24 h,48 h after CBP treatment and the end of CBP treatment.The efficacy of CBP treatment was evaluated in neonatal MOF.Results Gestational age of 6 neonates with MOF was 33 to 41 weeks,2 to 19 days old,2.25 to 3.36 kg birth weight.Primary disease was 4 cases of neonatal septicemia(1 case with congenital hereditary metabolic disease),2 cases of severe neonatal asphyxia.All 6 cases of venous catheter were smoothly done.CBP treatment persisted for 49 to 106 hours.Compared with before CVVHDF treatment,blood K+,blood urea nitrogen,creatinine significantly decreased at 12 h after CVVHDF treatment [(5.32 ± 1.84) mmol/L vs.(9.81 ±3.61) mmol/L,(9.0 ±3.4) mmol/L vs.(12.8 ±6.1) mmol/L,(99 ± 16) μmol/L vs.(176 ±25) μmol/L,P ＜0.05],and reached the normal range at 24 h after treatment,urine volume significantly increased at 24 h after treatment (P ＜ 0.05).PaO2/FiO2 reached 200 mmHg (1 mmHg =0.133 kPa) at 6 h after treatment and more than 300 mmHg at 24 h after treatment(P ＜0.05).Fifty percent of epinephrine intravenous dose were down-regulation at 12 h after treatment and stopped using epinephrine at 48 h after treatment.CBP treatment of 6 cases showed effective.Conclusion Application of bedside CBP treatment in neonatal MOF is safe,can effectively help neonates with MOF to skip over renal failure stage.

[ ABSTRACT] AIM:To investigate the protective effect of 1, 3-dicyclopentyl-1, 2, 3, 6-tetrahydropyrimidine-4, 5-dicarboxylic acid diethyl ester (ZL-5015) on lethal endotoxin-challenged mice and to explore the underlying mechanism. METHODS:Mouse model of lethal endotoxin challenge and endotoxemia were established by intraperitoneal administration of lipopolysaccharide (LPS) at a dose of 70 mg/kg to the C57BL/6J mice.Mouse peritoneal macrophages stimulated with LPS (10 mg/L) were used as an in vitro inflammatory model.The levels of interleukin-1β( IL-1β) , interleukin-10 ( IL-10) and tumor necrosis factor-α(TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA).Real-time PCR was used to evaluate the mRNA expression of the cytokines.RESULTS:Prophylactic treatment of the mice with ZL-5015 (100 and 200 mg/kg, ig) slightly increased the survival rate, extended the survival time, decreased the serum levels of IL-1βand TNF-α, and increased the serum level of IL-10 in the early stage of endotoxemia as compared with model group.The results of in vitro study demonstrated that treatment of the endotoxin-stimulated mouse peritoneal macrophages with ZL-5015 (10, 20 and 40μmol/L) inhibited the expression of IL-1βand TNF-αat both mRNA and protein levels but promoted the expression of IL-10 at both mRNA and protein levels.CONCLUSION: The tetrahydropyrimidine derivative ZL-5015 shows a moderate anti-endotoxin effect by increasing the survival rate and extending the survival time of the mice challenged by endotoxin, which may result from inhibition of the expression of pro-inflammatory cytokines such as IL-1βand TNF-α, and promotion of the expression of anti-inflammatory cytokine IL-10.

Objective Frontal resting EEG asymmetry was used to evaluate the gender effect of emotion regulation.Methods The resting EEG was recorded in 30 healthy volunteers (19-26 years old) by the guide 40 amplifier,and off-line analysis on EEG data were conducted by scan4.3 software.The statistical analysis were performed using SPSS 17.0.Results In normal human,frontal resting EEG alpha power was statistically significant(F=4.918,P =0.035).Asymmetry and gender interaction group (F =0.668,P =0.421),electrode point and gender interaction group (F =0.283,P =0.756),electrode point and asymmetry interaction group (F =1.418,P =0.260),electrode point,asymmetry and gender interaction group (F =1.164,P =0.327) had no statistical significance (P ＞ 0.05).The comparison of male and female asymmetry degree of each electrode point (F4/F3 group t =0.465,F8/F7 groupt=0.809,FP2/FP1 group t=1.542) had no statistical significance (P＞0.05).Conclusion Normal human brain hemispheres exist asymmetry.The asymmetry does not exists gender effect.In non-task state,frontal resting EEG alpha power asymmetry can not be recognized as the indicator of emotion regulation ability.

Objective To investigate the risk factors and prognosis of acute kidney injury (AKI) in elderly patients with sepsis in intensive care unit (ICU).Methods Clinical data of 108 elderly patients diagnosed as sepsis admitted in ICU in our hospital,from May 2010 to May 2014 were analyzed retrospectively.Patients were divided into two groups:the AKI group and the non-AKI group.Clinical characteristics,laboratory and physiologic data were compared between groups.Multivariate Logistic regression analysis was used to analyze the independent risk factors for AKI in these patients,and clinical outcome was retrospectively analyzed.Results Among the 108 elderly patients,60 patients developed AKI and the incidence was 55.6％.Baseline glomerular filtration rate (GFR) and mean arterial pressure (MAP) were lower in the AKI group than in non-AKI group (t=4.536 and 3.28).Prothrombin time (PT) (t=3.053),multiple organ dysfunction score (MODS) (t =2.201),acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score (t=3.423),the incidence of septic shock (x2 =5.400) and patients undergoing surgical operation within two weeks (x2 =5.625) were higher or longer in AKI group than in non-AKI group (all P＜0.05).Multivariate Logistic regression analysis showed that MAP (OR =0.833),baseline GFR (OR=0.776),MODS (OR=2.039) were independent risk factors for AKI occurrence.Hospital mortality,length of stay in ICU and hospitalization time were higher or longer in AKI group than in non-AKI group (P=0.001,0.026 and 0.042).Conclusions MAP,baseline GFR and MODS are the independent risk factors for AKI occurrence in elderly adults with sepsis in ICU.Hospital mortality,length of stay in ICU and hospitalization time are increased in sepsis patients combined with AKI.

Objective To investigate the changes of N-terminal pro-brain natriuretic peptide (NT-proBNP) in neonates with hypoxic-ischemic encephalopathy (HIE) complicated by myocardial ischemic injury. Methods Forty neonates with HIE ( 16 cases with concurrent myocardial injury and 24 cases without) were enrolled. Twenty healthy neonates were used as control. Plasma NT-proBNP levels were measured using enzyme immunoassay. Cardiac function was measured by echocardiography. Results ( 1 ) The mean plasma NT-proBNP levels in patients with myocardial injury[(350 ± 56) pmol/L]were significantly higher than those in patients without myocardial injury[(135 ± 37 ) pmol/L]and in the control group [(117 ±23) pmol/L](P ＜0. 05). (2) The NT-proBNP levels in mild,moderate and severe HIE neonates were ( 132 ±34) pmol/L, (247 ±43) pmol/L and (343 ±53) pmol/L. Compared with the control group,the NT-proBNP levels in the neonates with moderate and severe HIE significantly increased. There were significant differences in the NT-proBNP levels among the mild, moderate and severe HIE neonates ( P ＜ 0. 05 ).(3) In patients with myocardial injury,the NT-proBNP levels significantly decreased in the convalescent phase [(250±78) pmol/L]compared with those in the acute phase[(350±56) pmol/L](P ＜0.05). (4) The NT-proBNP levels were significantly related with left ventricular ejection fraction. Conclusion Plasma NT-proBNP levels increase in neonates with HIE complicated with myocardial ischemic injury in the acute phase.Detection of NT-proBNP levels maybe useful in the diagnosis of myocardial ischemic injury and severe HIE.

Objective To investigate the effects of permissive hypercapnia (PHC) strategy used in ventilated newborn swine with respiratory failure on cerebral blood flow (CBF) and tissue metabolism. Method Eighteen newborn swine were randomly (random number) divided into 3 groups (n = 6): PHC, normocapnia (NC) and normal control groups. In PHC (PaCO2 50～60 mmHg) and NC (PaCO2 35 ～ 45 mmHg) groups, newborn swine were ventilated for treating respiratory failure induced by meconium aspiration. CBF was measured by using colored microsphere tracking technique. Cerebral oxygen metabolism rate (CMRO2), cerebral glucose metabolism rate (CMRGlu), and cerebral lactate production (CLP) were measured. Results After ventilation for 6 hours and 12hours, CBF in NC group decreased more significantly than those did in control group, and CMRGlu and CLP increased more significantly than those did in control group. In NC group, CMRO2 decreased more prominently than it did in control group 12 hours later. The CBF/CMRGlu and CBF/CLP ratios in NC group were lower than those in control(P＜0.05). There was no significant difference in CBF/CMRO2 ratio between NC and control groups. After ventilation for 6 hours, CBF in PHC group was lower than those in control group. But after ventilation for 12hours, CBF in PHC group increased and there was no significant difference in CBF between PHC group and control group (P＞O.05). There were no significant differences in CMRGlu, CLP and CMRO2 between PHC group and control group. The CBF/CMRGlu and CBF/CLP ratios in PHC group were lower than those in control, but higher then those in NC group (P＜0.05). There was no significant difference in CBF/CMRO2 ratio between PHC and control groups. Conclusions The reduction of cerebral blood flow and the disturbance of CBF autoregulation disturbance occur in ventilated newborn swine with hypoxemia respiratory failure. PHC may attenuate the reduction in CBF and the disturbance of CBF autoregulation.

Objective:To study the apoptosis of T lymphocyte subsets of peripheral blood in systemic lupus erythematosus(SLE) and the correlated pathogenesis.Methods:The percentages of T lymphocyte subsets,the positive expression rates of Fas/FasL on T lymphocyte subsets,and the apoptosis of T lymphocyte subsets were determined by three-colorflow cytometry.The level of serum IL-10 was analyzed by ABC-ELISA.IL-10 antibody and FasL antibody were added respectively into the 48 hours' culture of 10 SLE patients' PBMCs in vitro,whose serum IL-10 significantly increased,and then,the changes of T lymphocyte subsets of SLE PBMCs were determined by three-colorflow cytometry.Results:1) In SLE,mainly in hyperactive SLE,the apoptosis of CD4+ T lymphocytes increased significantly(P