Objective To compare bolus infusion and replenishment using real low mechanical index contrast enhanced ultrasound in assessing the change of renal cortical perfusion.Methods Using dopamine (i.v.) at the dose of 0.5,2.0,5.0μg · kg- 1 · min- 1 to change renal blood perfusion of 20 rabbits,then during bolus or contant injection of SonoVue,at coded pulse inversion mode,real-time contrast ultrasound was performed,the latter method needed destroying microbubble at a high MI when amplitude reach a steady state,then recording the replenishment,peak intensity(A) and time to peak (PPT) were obtained through raw time-intensity curve,and slope rate of TIC(k) was acquired by curve fitting,standard effective renal plasma flow(ERPF) was measured through 4-aminohippuric acid clearancerate method,meanwhile correlations between ERPF and parameters were analyzed,as well as the paired samples t test for each parameter before and after dopamine administration.Results The ascending branchs of raw TIC of bolus infusion increased sharply and were approximately straight,then descended gradually,while that of replenishment looked like two straightlines with different slopes,then stayed horizontal Both the value of A of two methods were positively correlated with ERPF ( r b =0.85,r re =0.66),and were different at the same ERPF,meanwhile the value of TTP were negatively correlated with ERPF( r b =-0.92,r re =- 0.76),and there were no statistically difference between the two methods.k from Gamma fitting was far from correct,while k from exponential fitting was apparently correlated with ERPF ( r re =0.77 ).Conclusions Both bolus injection and constant injection-replenishment method can assess renal cortical blood perfusion,TIC parameters A and TTP represent regional blood volume fraction and microbubble velocity respectively.Bolus-infusion with real low mechanical index is more precise and available.Comparing with k,TTP is more appropriate to reflect perfusion velocity.

Objective To investigate the feasibility of transfecting gene into HepG2 by therapeutic ultrasound combined with microbubble,and to explore the optimal ultrasonic parameters for high transfection efficiency.Methods HepG2 cells were cross-interval planted in 24-well plates.EGFP plasmid DNA and microbubbles were added to the cultured HepG2 and three parameters of the therapeutic ultrasound were optimized.Firstly,set ultrasonic intensity gradient (group A,from A1 to A5),which were 0.4 W/cm,0.8 W/cm2,1.2 W/cm2,1.6 W/cm2 and 2.0 W/cm2 respectively.Secondly,set the duty cycle gradient group (group B,from B1 to B3),which were 10％,20％ and 50％ respectively.Lastly,set the exposure time group(group C,from C1 to C3),which were 30 s,90 s and 180 s.After 24 hours,the expression of GFP was observed by fluorescence microscopy,the transfection rates was detected by flow cytometry,the cell death were assessed by trypan blue exclusion.Results The plasmid transfection efficiency was varied under different ultrasonic parameters.Within a certain range,the increasing of parameters can improve the transfection efficiency,but when the parameters were too large (eg.the intensity＞1.6 W/cm2 or 50％ duty cycle),the actual transfection efficiency decreased due to the increased cell death.When the ultrasonic intensity was 1.2 W/cm2,the transfection efficiency and mortality were better than the other subgroups of group A.When the duty cycle was 20％,the transfection efficiency and mortality rate were better than the other subgroups of group B.Continue to increase the exposure time over 90 s was not statistically significant (P ＞0.05) for transfection efficiency and cell mortality.Conclusions The ultrasound-targeted microbubble destruction is an efficient method for gene delivery in vitro.The transfection efficiency vary greatly under different parameters,so optimization parameters is conducive to the promotion of gene transfection.

The association rate constant and dissociation rate constant are important parameters of the drug-cyclodextrin supermolecule systems, which determine the dissociation of drugs from the complex and the further in vivo absorption of drugs. However, the current studies of drug-cyclodextrin interactions mostly focus on the thermodynamic parameter of equilibrium constants (K). In this paper, a method based on quantitative high performance affinity chromatography coupled with mass spectrometry was developed to determine the apparent dissociation rate constant (k(off,app)) of drug-cyclodextrin supermolecule systems. This method was employed to measure the k(off,app) of meloxicam and acetaminophen. Firstly, chromatographic peaks of drugs and non-retained solute (uracil) on β-cyclodextrin column at different flow rates were acquired, and the retention time and variance values were obtained via the fitting the peaks. Then, the plate heights of drugs (H(R)) and uracil (H(M,C)) were calculated. The plate height of theoretical non-retained solute (H(M,T)) was calculated based on the differences of diffusion coefficient and the stagnant mobile phase mass transfer between drugs and uracil. Finally, the k(off,app) was calculated from the slope of the regression equation between (H(R)-H(M,T)) and uk/(1+k)2, (0.13 ± 0.00) s(-1) and (4.83 ± 0.10) s(-1) for meloxicam and acetaminophen (control drug), respectively. In addition, the apparent association rate constant (k(on,app)) was also calculated through the product of K (12.53 L x mol(-1)) and k(off,app). In summary, it has been proved that the method established in our study was simple, efficiently fast and reproducible for investigation on the kinetics of drug-cyclodextrin interactions.
Acetaminophen ; chemistry ; Chromatography, Affinity ; Drug Interactions ; Kinetics ; Mass Spectrometry ; Thermodynamics ; Thiazines ; chemistry ; Thiazoles ; chemistry ; beta-Cyclodextrins ; chemistry

OBJECTIVETo compare the therapeutic effects of acupuncture and Motilium on diabetic gastroparesis (DGP).

METHODSSeventy-two cases of DGP were randomly divided into a treatment group and a control group. The treatment group were treated with needling method for harmonizing spleen-stomach as main, with Quchi (LI 11), Hegu (LI 4), Zhongwan (CV 12), Zusanli (ST 36), Fenglong (ST 40), Yinlingquan (SP 9), Sanyinjiao (SP 6), Xuehai (SP 10), Diji (SP 8), and others selected, twice each day, 10 days constituting one course, with an in terval of 2 days; the control group were treated with oral administration of Motilium 10 mg, 3 times each day, 30 min before meals.

RESULTSThe total effective rate of 91.7% in the treatment group was better than 77.8% in the control group (P < 0.05).

CONCLUSIONThe therapeutic effect of the needling method for harmonizing spleen-stomach on diabetic gastroparesis is better than that of Motilium.

Acupuncture Therapy ; methods ; Adult ; Diabetes Complications ; therapy ; Female ; Gastroparesis ; therapy ; Humans ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Spleen ; physiopathology ; Stomach ; physiopathology

OBJECTIVETo investigate the clinicpathologic features and diagnosis of plasmablastic lymphoma (PBL).

METHODSEleven cases of PBL were collected and followed up, with review of the literature. HIV and EBV status and their relationships with the tumor were specially compared as well.

RESULTSIn the current cohort, 10 patients were serologically HIV negative; the male to female ratio was 8 to 3, and the median age was 57 years. Ten cases showed extranodal involvement and one case was nodal based. At presentation, five patients had mid-facial involvement, including sinonasal area (3 cases) and oral cavity (2 cases). Histologically, six were PBL of oral mucosa type, and five were PBL with plasmacytic differentiation. In all cases, the neoplastic cells expressed CD138 and MUM-1, and were negative for CD20 and CD3ε; the median Ki-67 index was 80%. Five cases were EBER1/2 in situ hybridization positive. IgH or/and Igκ gene rearrangement was detected in all five cases examined.

CONCLUSIONSMost patients were no congenital or acquired immunodeficiency in the retrospective study. Of the died patients, EBER1/2 in situ hybridization were negative and their disease staging were Ⅳ, The neoplastic cells were immunoblastic or plasmablastic, sometimes the plasmacytoid cell can be seen and the neoplastic cell had mature plasma cell phenotype, the pathologic diagnosis of the lymphoma is still controversial now. Differentiate with plasma cell neoplasm is difficult, it is necessary to accumulate more cases for advanced study and observation in the future.

Female ; Gene Rearrangement ; Humans ; In Situ Hybridization ; Male ; Middle Aged ; Multiple Myeloma ; Plasma Cells ; Plasmablastic Lymphoma ; diagnosis ; pathology ; RNA, Viral ; metabolism ; Retrospective Studies

Objective To investigate the influence of EMR and ESD of endoscopic surgery on perioperative clinical parameters, complete resection rate and complications of patients with neuroendocrine tumors of digestive tract. Methods 40 patients with neuroendocrine tumors of digestive tract were chosen from June 2009 to June 2016 and randomly divided into 2 groups: A group (20 patients) with EMR and B group (20 patients) with ESD; and the operation time, the treatment cost, the lesion size, the lesion thickness, the complete resection of tumor, the negative rate of vertical margin and the complication incidence of the two groups were compared. Results The operation time and the treatment cost of B group were significant better than A group (P < 0.05). There was no significant difference in the lesion size and the lesion thickness between the two groups (P < 0.05). The completed resection rate of B group were significant higher than A group (P < 0.05). There was no significant difference in the negative rate of vertical margin between the two groups (P < 0.05). The complication incidence of B group were significant higher than A group (P < 0.05). Conclusion EMR and ESD of endoscopic surgery in the treatment of patients with neuroendocrine tumors of digestive tract possess the same clinical effects; EMR application can efficiently shorten the operation time and decrease the economic burden and ESD application maybe helpful to reduce the complication risk.

To provide the profiles of metabolism of mitomycin C (MMC) by human liver microsomes in vitro, MMC was incubated with human liver microsomes, then the supernatant component was isolated and detected by HPLC. Types of metabolic enzymes were estimated by the effect of NADPH or dicumarol (DIC) on metabolism of MMC. Standard, reaction, background control (microsomes was inactivated), negative control (no NADPH), and inhibitor group (adding DIC) were assigned, the results were analyzed by Graphpad Prism 4. 0 software. Reaction group compared with background control and negative control groups, 3 NADPH-dependent absorption peaks were additionally isolated by HPLC after MMC were incubated with human liver microsomes. Their retention times were 10. 0, 14. 0, 14. 8 min ( named as Ml, M2, M3) , respectively. Their formation was kept as Sigmoidal dose-response and their Km were 0. 52 (95% CI, 0. 40 - 0.67) mmol x L(-1), 0. 81 (95% CI, 0. 59 - 1. 10) mmol x L(-1), 0. 54 (95% CI, 0. 41 -0. 71) mmol x L(-1) , respectively. The data indicated that the three absorption peaks isolated by HPLC were metabolites of MMC. DIC can inhibit formation of M2, it' s dose-effect fitted to Sigmoidal curve and it' s IC50 was 59. 68 (95% CI, 40. 66 - 87. 61) micromol x L(-1) , which indicated DT-diaphorase could take part in the formation of M2. MMC can be metabolized by human liver microsomes in vitro, and at least three metabolites of MMC could be isolated by HPLC in the experiment, further study showed DT-diaphorase participated in the formation of M2.
Antibiotics, Antineoplastic ; metabolism ; Chromatography, High Pressure Liquid ; methods ; Dicumarol ; pharmacology ; Dose-Response Relationship, Drug ; Enzyme Inhibitors ; pharmacology ; Humans ; Microsomes, Liver ; drug effects ; enzymology ; metabolism ; Mitomycin ; metabolism

OBJECTIVE The purpose of the present study was to investigate the impact of fluvas-tatin formulation on the pharmacokinetics-genetic polymorphis relationship. METHODS We compared the difference between the pharmacokinetics of fluvastatin as an extended-release (ER) 80 mg tablet and an immediate-release(IR)40 mg capsule in terms of drug metabolism enzyme and transporter ge-netic polymorphisms. In this open-label, randomized, two-period, two-treatment, crossover study, ef-fects of BCRP, SLCO1B1, MDR1, CYP2C9, and CYP3A5 polymorphisms on the pharmacokinetics of fluvastatin were analyzed in 24 healthy individuals.Each treatment duration was 7 days with a washout period of 7 days between the crossover.Serum concentration of fluvastatin was evaluated using high-performance liquid chromatography-tandem mass spectrometry. RESULTS The SLCO1B1 T521C genotype had no statistically significant effect on IR 40 mg capsule of fluvastatinafter single or repeated doses.However,for the ER 80 mg tablet,the SLCO1B1 T521C genotype correlated with the AUC0-24of repeat doses (P=0.01). The CYP2C9*3 genotype correlated with the AUC0- 24after the first dose IR 40 mg capsule (P<0.05); however, the difference between CYP2C9*1/*1 and CYP2C9*1/*3 was not statistically significant after repeated doses. CONCLUSION The effect of SLCO1B1 T521C on fluvas-tatin exposure was observed and was more profound in ER and repeated dose administration than in IR and single dose administration.We recommend that formulation should be incorporated into future pharmacogenomics studies and clinical implication guidelines.

OBJECTIVETo accurately evaluate the early hemodynamic status of neonates who undergo complex neonatal cardiac surgery, through monitoring the cardiac index (CI), serum lactate (Lac), mixed venous oxygen saturation (SvO(2)).

METHODSFrom January to November 2007, haemodynamic data of 80 patients who had open heart surgery for congenital heart disease were analyzed within 48 hours after operation. Of the 80 patients, 47 were neonates, their age ranged from 3 days to 29 days [mean (21.98 + or - 8.15) days] and weight ranged from 2.6 kg to 4.2 kg [mean (3.51 + or - 0.39) kg]. As the control group, 33 young infants at the age of 30 days to 180 days [mean (76.36 + or - 24.79) days] with body weight ranged from 3.1 kg to 6.0 kg [mean (4.59 + or - 0.59) kg] were also enrolled. The value of CI derived from pulse contour and was calculated by using the PiCCO system. Meanwhile, measurements of serum lactate level and SvO(2) were recorded. Serial measurements of the cardiac output were performed for the neonates.

RESULTSCI in survivors of neonates (2.01 + or - 0.35) L/(min x m(2)) was lower than that of the infants (2.26 + or - 0.39) L/(min x m(2)) after cardiac surgery (P < 0.05) at 2 h, 6 h postoperatively. However, urine output remained normal. The value of pulse pressure in neonates was less than that in young infants. Serum lactate level in neonates was significantly higher than that of young infants during cardiac surgical procedures (P < 0.01) at 12 h postoperatively; the SvO(2) was more than 60% postoperatively in survived neonates, there was no significant difference (P > 0.05) in SvO(2) between neonates and young infants during preoperative and postoperative periods. There was a positive correlation between CI and SvO(2). Four neonates and 1 young infant died after surgical treatment, surgical mortality was 8.5% and 3.0%, respectively. The deaths of the neonates were related to the cardiocirculatory function decompensation, unrelieved severe acidosis preoperatively, and the transposition of great artery with coronary artery malformation and longer cardiopulmonary bypass. The patients with significantly high arterial blood lactate levels during the first 6 - 12 hours postoperatively had poor outcome. Lactate levels were higher than 10 mmol/L and SvO(2) less than 50% in neonates who developed multiple organ system failure. One young infant died of sudden arrhythmia after surgical treatment, whose death may be related the surgical procedure itself with pulmonary artery banding and blalock-taussig shunt leading to increased preload and afterload of the heart.

CONCLUSIONSElevated serum lactate level postoperatively may reflect intraoperative tissue hypoperfusion. Serial blood lactate level measurements may be an accurate predictor of clinical outcomes in children after pediatric open heart surgery. Mixed venous oxygen saturation changes more rapidly than other standard hemodynamic variables. The higher mortality of neonates with congenital heart disease is related to the malformation complexity itself and illness severity.

Cardiac Surgical Procedures ; Female ; Heart Defects, Congenital ; blood ; mortality ; surgery ; Hemodynamics ; Humans ; Infant, Newborn ; Oximetry ; Postoperative Period ; Stroke Volume ; Survival Rate

OBJECTIVENeurally adjusted ventilatory assist (NAVA) is a new mode of mechanical ventilation that delivers ventilatory assist in proportion to neural effort. This study aimed to compare the hemodynamic safety, oxygenation and gas exchange effects ventilated with NAVA and with pressure support ventilation (PSV) in infants who underwent open-heart surgery.

METHODSTwenty-one infants who underwent open-heart surgery for congenital heart disease (mean age 2.9+/- 2.1 months and mean weight 4.2+/- 1.4 kg) were enrolled. They were ventilated with PSV and NAVA for 60 minutes respectively in a randomized order. The hemodynamic, oxygenation and gas exchange effects produced by the two ventilation modes were compared.

RESULTSThree cases failed to shift to NAVA because of the bilateral diaphragmatic paralysis after operation. In the other 18 cases, there were no significant differences in the heart rate (HR), systolic blood pressure (BPs) and central venous pressure (CVP) in the two ventilation modes. The PaO2/FiO2 (P/F) ratio in NAVA was slightly higher than in PSV, but there was no statistical difference. PaCO2 did not show significant differences in the two modes. The peak inspiratory pressure (PIP) and electrical activity of the diaphragm (EAdi) in NAVA were significantly lower than in PSV. The EAdi signal after extubation was higher in infants who needed reintubation or intervention of noninvasive mechanical ventilation than in those who were extubated successfully (30.0+/- 8.4 microV vs 11.1+/- 3.6 microV; P<0.01).

CONCLUSIONSAs the first study of application of NAVA in infants in China, this study shows that NAVA has the same homodynamic effects as PSV. However the PIP for maintaining the same level of PaCO2 in NAVA is significantly lower than that in the traditional PSV. Monitoring the EAdi signal after extubation may show the risks of reintubation or intervention of noninvasive mechanical ventilation.

Female ; Heart Defects, Congenital ; physiopathology ; surgery ; Hemodynamics ; Humans ; Infant ; Male ; Respiration, Artificial ; methods