OBJECTIVE To establish a combined pharmacokinetic(PK)-pharmacodynamic(PD)model for knee osteoarthritis(KOA)of crossbow drug microemulsion multi-components(benzoylmesaconine,benzoylhypacoitine,mesaconitine,periplocin,neo-chlorogenic acid,vanillic acid,chlorogenic acid),and elucidate the dynamic changes in the KOA rats and the interrelation with the e-lapsed efficacy of the drug.METHODS A KOA rat model was induced by 4%papain;the PK process of crossbow medicine microe-mulsion components in rat synovial fluid was analyzed by UPLC to establish a PK model;the contents of MMP-3,MMP-13,TNF-α and IL-1β in KOA rats at different time points after administration were determined by ELISA analysis to establish a PD model;Phoe-nix WinNonlin software was used to fit the PK and PD data to obtain a PK-PD model.RESULTS PK results showed that the multi-components of the microemulsion were slowly absorbed in the joint cavity and gradually reached the peak value within 3-5 h.The Cmax of benzoylmesaconine,benzoylhypacoitine mesaconitine,periplocoside,neochlorogenic acid,vanillic acid and chlorogenic acid were 1.23,1.48,1.62,4.67,0.93,1.25 and 2.35 μg·mL-1,respectively;the area under the drug-time curve(AUC0-11)was 2.58,4.04,3.54,12.15,2.51,2.41 and 4.11 h·μg·mL-1,respectively.PD results showed that at different time points after adminis-tration,the contents of MMP-3,IL-1β,TNF-α,and MMP-13 decreased to varying degrees,among which MMP-3 decreased insig-nificantly,with significant differences only at 6 h;the contents of the remaining IL-1β,TNF-α,and MMP-13 decreased significantly(P<0.05,P<0.01),and showed the phenomenon of lagged efficacy;the PK-PD binding model showed that the drug concentration of the multi-component drug in the crossbow medicine microemulsion could be well fitted with its drug efficacy data.CONCLUSION The established PK-PD binding model can predict the drug efficacy changes after administration,and provides a corresponding refer-ence for the crossbow medicine microemulsion treatment of KOA.

OBJECTIVE To establish a combined pharmacokinetic(PK)-pharmacodynamic(PD)model for knee osteoarthritis(KOA)of crossbow drug microemulsion multi-components(benzoylmesaconine,benzoylhypacoitine,mesaconitine,periplocin,neo-chlorogenic acid,vanillic acid,chlorogenic acid),and elucidate the dynamic changes in the KOA rats and the interrelation with the e-lapsed efficacy of the drug.METHODS A KOA rat model was induced by 4%papain;the PK process of crossbow medicine microe-mulsion components in rat synovial fluid was analyzed by UPLC to establish a PK model;the contents of MMP-3,MMP-13,TNF-α and IL-1β in KOA rats at different time points after administration were determined by ELISA analysis to establish a PD model;Phoe-nix WinNonlin software was used to fit the PK and PD data to obtain a PK-PD model.RESULTS PK results showed that the multi-components of the microemulsion were slowly absorbed in the joint cavity and gradually reached the peak value within 3-5 h.The Cmax of benzoylmesaconine,benzoylhypacoitine mesaconitine,periplocoside,neochlorogenic acid,vanillic acid and chlorogenic acid were 1.23,1.48,1.62,4.67,0.93,1.25 and 2.35 μg·mL-1,respectively;the area under the drug-time curve(AUC0-11)was 2.58,4.04,3.54,12.15,2.51,2.41 and 4.11 h·μg·mL-1,respectively.PD results showed that at different time points after adminis-tration,the contents of MMP-3,IL-1β,TNF-α,and MMP-13 decreased to varying degrees,among which MMP-3 decreased insig-nificantly,with significant differences only at 6 h;the contents of the remaining IL-1β,TNF-α,and MMP-13 decreased significantly(P<0.05,P<0.01),and showed the phenomenon of lagged efficacy;the PK-PD binding model showed that the drug concentration of the multi-component drug in the crossbow medicine microemulsion could be well fitted with its drug efficacy data.CONCLUSION The established PK-PD binding model can predict the drug efficacy changes after administration,and provides a corresponding refer-ence for the crossbow medicine microemulsion treatment of KOA.

OBJECTIVE To investigate the pharmacokinetic characteristics of crossbow microemulsion in rabbit skin.METH-ODS The concentrations of chlorogenic acid,benzoyl new aconitine,periplocin and new aconitine were determined by UPLC.The effects of temperature,perfusion speed and mass concentration on the recovery rate of the probe were investigated by incremental and decrement methods,the changes of multi-component content in the dialysate at different time points after transdermal administration of crossbow microemulsion were determined by UPLC,and DAS 2.0 software was used to process the data.RESULTS The recovery rate of the probe increased with increasing temperature,and the higher the flow rate,the lower the recovery rate.The pharmacokinetic parameters of chlorogenic acid,benzoyl new aconitine,periplocin and new aconitine in microemulsion Cmax were(3.24±0.39)(1.04±0.29)(4.78±2.15)(2.86±0.55)μg·mL-1,respectively,and in AUC0-∞ were(52.42±30.84)(7.70±3.73)(42.23±13.93)(22.68±12.51)h·mg·mL-1,respectively.CONCLUSION A real-time in vivo microdialysis sampling technique was first used and a UPLC detection technique was established to study the skin pharmacokinetics of multi-components of crossbow microe-mulsion after transdermal administration,which provides a reference for the follow-up investigation and application of crossbow microe-mulsion.

Objective The study was designed to analyze the risk factors for perioperative adverse events in Ebstein's a-nomaly(EA) after cone construction.Methods A retrospective analysis was performed on EA cases undergoing cone con-struction in pediatric heart center of Beijing Anzhen Hospita from January 2010 to January 2017.Patients were divided into group A( no adverse events occurred) and group B( adverse events occurred) according to the presence or not of perioperative adverse events.Univariate and multivariate logistic regression analysis was performed with 9 preoperative and intraoperative var-iables as the predicted risk factors.Results The incidence of adverse events was 13.1％.Univariate logistic regression analy-sis showed that preoperative percutaneous oxygen saturation(SpO2)≤0.90(P=0.001, OR=10.578) and extracorporeal cir-culation time(P=0.034, OR=1.021) were risk factors for perioperative adverse events.Results of multivariate logistic re-gression analysis: preoperative SpO2≤0.90 was an independent risk factor for perioperative adverse events(P=0.002, OR=9.108).In 64 cases(64.6％) with atrial septum defect, there was no significant correlation between preoperative SpO2 and preoperative tricuspid regurgitation(P=0.838, r =0.026).Conclusion Preoperative SpO2≤0.90 is an independent risk factor for adverse events in the perioperative period of cone reconstruction .It is a simple and efficient method to evaluate the operation difficulty and determine the prognosis by SpO 2 .

Objective To explore the distribution of lactate and base excess in children with Tetralogy of Fallot in perio-perative period, its dynamic variation and its relationship with prognosis.Methods Perioperative arterial lactate level was dy-namically monitored in 1 552 children with tetralogy of Fallot.According to the prognosis, 1 505 subjects were assigned to sur-vive group, and 47 subjects to nonsurvive group.The lactate and base excess levels of all subjects were collected after induction (T1), after protamine administration(T2), and 24 h(T3) after surgery in the intensive care unit(ICU).Results The pa-tients who could not survive showed significant elevated lactate levels as compared to patients who survived after surgery [(7.91 ±5.76)mmol/L vs.(1.20 ±0.51)mmol/L, P＜0.05].However, in nonsurvivors, the BE value decreased signifi-cantly in the ICU period in comparison to survivors[(－1.91 ±5.09)mmol/L vs.(2.52 ±2.85)mmol/L, P＜0.05].Logis-tic regression analysis was performed, indicating the elevated lactate and depressed base excess levels measured 24 h after sur-gery were independent risk factors.Conclusion The dynamic monitoring of lactate and base excess levels in the perioperative period in patients with tetralogy of Fallot were sensitive indicators to assess severity , to guide treatments, and for the prognosis. In the perioperative period, when the lactate increased and(or) base excess levels decreased, the mortality rate increased as well.lactate and base excess levels measured 24 h after surgery in the ICU were independent risk factors that significantly in-creased the mortality rate.

Asian Continental Ancestry Group ; Hearing Loss ; genetics ; Humans ; Mutation ; genetics ; Pedigree ; RNA, Ribosomal ; genetics

Objective To study the beneficial effect and mechanism of Alcea rosea roots in nephrolithiasis model in-duced by 1%ethylene glycol in rats. Methods We randomly divided 60 male Wistar rats into six groups,including control group, model group, Alcea rosea roots lower-dose preventive group, Alcea rosea roots high-dose preventive group, Alcea ro-sea roots lower-dose curative group, Alcea rosea roots high-dose curative group. Control group was free to access food and water;model group was given 1%ethylene glycol drinking water and was fed with normal diet, preventive group was given 1%ethylene glycol drink and Alcea rosea roots in low (250 mg/kg) or high dose (500 mg/kg) each day, curative group re-ceived 1%ethylene glycol drink each day and Alcea rosea roots in low or high dose from day 15 to day 28. At the end of the experiment, various renal functional and injury markers such as urine volume, calcium, phosphate, magnesium, urea, creati-nine, and oxalate were evaluated using urine, serum, and kidney homogenates. The kidneys were removed and prepared for histological evaluation of calcium oxalate deposits. Results In model groups, urine output, urea, creatinine, 24 h urine Ca2+, and oxalate and MDA were increased compared to those in control group(P＜0.05). GSH and SOD were increased in preventative and curative groups compared to those in the model group(P ＜ 0.05). The urea, creatinine, 24 h urine Ca2+, urine oxalate, MDA were reduced in preventive and curative groups compared to those in the model group(P＜0.05). The number and size of calcium oxalate crystal deposits were also less and smaller, and the kidney damage was less severe in pre-ventive and curative groups compared to in the model group. Conclusion The extract of Alcea rosea roots can prevent and treat calcium oxalate urinary stone formation in rats and protect renal function.

Objective To evaluate the effect of proper nutritional therapy guided by indirect caloimetry . Methods According to the digitaltable ,70 critically ill patients whose APACHE II >5 were randomly divided into oberserving ( nutritional therapy guided by indirect caloimetry ) and control groups ( nutritional therapy guided by harris-benedict formula),each group 35 cases.The results of nutrition support were analysed .Results TP,MAMC,ALB were higher than that before treatment in oberserving group (all P<0.05),the MAMC was also higher than that in control groups(P<0.05).There was no significant difference in Hb and TSF after treatment IN oberserving group (all P>0.05).Conclusion The nutritional therapy guided by indirect caloimetry by harris-benedict formula have the some nutritional effect in critically ill patients .

BACKGROUND: Hyperpolarization-activated cyclic nucleotide-gated (HCN) current plays an important role in regulating heart spontaneous pulsation.OBJECTIVE: To observe target gene expression and electrophysiological characteristics of pig bone marrow mesenchymal stem cells (BMSCs) transfected with hyperpolarization-activated cyclic nucleotide-gated channel 2 (HCN2) gene recombinant adenovirus.DESIGN, TIME AND SETTING: Cell-gene in vitro study was performed at the Laboratory of Thoracic and Cardiovascular Surgery,Second Military Medical University of Chinese PLA from July 2007 to March 2008.MATERIALS: Yorkshire pig was supplied by Animal Institute, Second Military Medical University of Chinese PLA. HCN2 plasmid was presented by Professor Dario DiFrancesco from Italy. Recombinant adenovirus Ad.HCN2 was constructed and stored using Ad5 in this laboratory.METHODS: Pig BMSCs were isolated with combination of gradient centrifugation of Percoll and adherent treatment in vitro.Ad.HCN2 was transfected at multiplicity of infection=50. We also set non-transfection and transfected Ad.Null groups.MAIN OUTCOME MEASURES: Expression of HCN2 mRNA was detected with RT-PCR, and expression of HCN2 channel protein was examined with immunofluorescent staining. Electrophysiology of HCN2 channel protein was measured with whole-cell patch clamp.RESULTS: No amplified fragments were found in the non-transfection and transfected Ad.Null groups, but amplified fragments were determined at 250-500 bp following Ad.HCN2 amplification, which was the same as plasmid carrying HCN2 gene. Staining strength of cell nuclei following transfection was significantly weaken compared with cell membrane and plasma, which showed identical distribution as HCN2 protein. No HCN2 protein was detected in the non-transfection and transfected Ad.Null groups.Pacemaker current could be recorded with a whole-cell patch clamp. It was fully activated around -140 mV with an activation threshold of -60 mV, presenting voltage dependence. CsCI (4 mmol/L) reversibly blocked the inward currents. No pacemaker current was detected in the non-transfection and transfected Ad.Null groups.CONCLUSION: The HCN2 recombinant adenovirus carrier was transferred into serial subcultivation porcine bone marrow mesenchymal stem cells. HCN2 channel protein has been expressing. Pacemaker current could be recorded with a whole-cell patch clamp.

ing microecological preparation,or continuously pumping EN fluid into the stomach or jejunum may reduce the incidence of diarrhea.