This study was aimed to develop a maximum a posteriori Bayesian (MAPB) estimation method to estimate individual pharmacokinetic parameters based on D-optimal sampling strategy. Meanwhile, the performance of MAPB was compared with the multiple linear regression (MLR) method in terms of accuracy and precision. Pharmacokinetic study of pioglitazone was employed as the example case. The population pharmacokinetics was characterized by nonlinear mixed effects model (NONMEM). The sparse sampling strategy (1-4 points) was identified by D-optimal algorithm using WinPOPT software. The simulated data generated by Monte Carlo method were used to access the performance of MAPB and MLR. As the number of samples per subject decreased, the accuracy and precision of MAPB method tended to get worse. The estimation for CL and Vby MAPB using D-optimal two-point design had less bias with low inter-individual variability, and had more bias and imprecision with high residue variability. The estimation of AUC by MAPB using D-optimal 2 points design had similar accuracy and precision to MLR. However, MAPB estimation was better than MLR while adjusting the sampling time to one hour. Overall, the MAPB method had similar predictive performance as MLR, but MAPB could provide more pharmacokinetic information with higher sampling flexibility.

Infection is one of the most important complications of acute stroke, and it is an independent risk factor for resulting in stroke worsening. Growing evidence has indicated that acute stroke patients suffer an impaired peripheral immune response, i.e. stroke-induced immunodepression system (SIDS). SIDS is characterized by the rapid and sustained cellular immunodepression after acute stroke, which is mainly presented as wide apoptosis and dysfunction of lymphocyte. Multiple reasons activate the sympathetic nervous system, and thus cause SIDS. SIDS weakens the effective defense against the invasion of pathogens in the human body, resulting in the increased infection and mortality rate. However, SIDS also has protective effect on the human body. It can prevent the excessive inflammatory response in the injured brain tissue. A better understanding of the complex relationships between the central nervous system and the immune system are promising to provide more effective treatment methods for patients with acute stroke.

During the installation of a pipe pile, the soil around the pile will be squeezed out. This paper deals with this squeezing effect of open-ended pipe piles using the cylindrical cavity expansion theory. The characteristics of soil with different tension and compression modnli and dilation are involved by applying the elastic theory with different moduli and logarithmic strain. The closed-form solutions of the radius of the plastic region, the displacement of the boundary between the plastic region and the elastic region and the expansion pressure on the external surface of the pipe piles are obtained. When obtaining these solutions, the soil ping in the open-ended pipe pile is considered by employing an incremental filling ratio to quantify the degree of soil plugging. Moreover, the effects of the ratio of tension and compression moduli, angle of dilation and incremental filling ratio on the radius of the plastic region and the expansion pressure on the external surface of the pipe pile are investigated. The parametric analyses show that it is necessary and important to consider the difference between the tension modulus and compression modulus, dilation angle and incremental filling ratio for studying the squeezing effect of open-ended pipe pile installation. It is concluded that the analytical solutions presented in this paper are suitable for studying the squeezing effect of open-ended pipe piles.

Objective To investigate the relationship between the microsatellite polymorphism of cytotoxic T lymphocyte associated antigen-4 (CTLA-4) gene and inflammatory bowel disease(IBD) patients in Zhejiang province. Methods One hundred and eighteen IBD patients without consanguinity (99 patients with ulcerative colitis, 19 patients with Crohn's disease) and 140 healthy controls were studied. The (AT) repeats in the 3' untranslated region of exon 4 of CTLA-4 gene were amplified by allele-specific PCR. The amplified products were electrophoresed with 12% polyacrylamide gel, followed by silver staining. Results Twenty alleles were found in IBD patients and healthy controls. The frequency of 122 bp allele was higher in patients with ulcerative colitis (P=0.0001/Pc=0.0025, OR= 11.393, 95% CI:2.574-50.429) and Crohn's disease (P=0.0003/Pc=0.0050, OR=21.061, 95% CI:3.927-112.94) than that in healthy controls. Conclusion CTLA-4 gene microsatellite polymorphism was obviously associated with IBD in Zhejiang province.

0.05)in sex,age and volume of lesions.Over a course of treatment the average volume of thyroid adenomas of each group significantly(P

Objective To explore the independent risk factors related to acute post-stroke pneumonia.Methods A total of 545 inpatients with acute stroke in Shanghai First People's Hospital Affiliated to Shanghai Jiaotong University and East Hospital Affiliated to Tongji University during July 1,2009 to June 30,2011 were enrolled.Single-factor analysis was performed to identify the risk factors of acute post-stroke pneumonia. According to the results of single-factor analysis and relevant professional knowledge,fitting multi-factor non-conditional Logistic regression model,adjusting the relevant confounded factors,the independent risk factors were analyzed.Results The incidence of acute post-stroke pneumonia was 11.0％ (60/545).The independent risk factors of acute post-stroke pneumonia were:age ≥ 80 year ( OR =6.024,95％ CI:1.923 - 18.868,P =0.002 ),hemorrhagic stroke ( OR =3.546,95％ CI:1.266 -9.901,P =0.016),stay in bed ( OR =4.295,95％ CI:1.642 - 11.233,P =0.003 ),baseline Glasgow coma scale ≤8 ( OR =5.127,95％ CI:1.377 - 19.090,P =0.015 ),baseline Barthel index ＜50 ( OR =8.403,95％ CI:1.468 -47.619,P =0.017 ),malnutrition ( OR =10.625,95％ CI:3.260 -34.631,P =0.000 ),baseline fasting plasma glucose ≥ 7.0 mmol/L ( OR =10.000,95％ CI:3.115 -32.258,P =0.000); and early rehabilitation was the protective factor (OR =0.159,95％ CI:0.055 -0.466,P =0.001 ).Conclusions The incidence of acute post-stroke pneumonia is high,and it is relatedwith many independent risk factors.Comprehensive interventions may contribute to early identify and prevent acute post-stroke pneumonia.

The ketoreductase (KR) domain in the first extending module of the polyketide synthase (PKS) catalyzes the reductions of both an α-keto group and a β-keto group in the biosynthesis of bacillaene, suggesting the intrinsic substrate promiscuity. In order to further investigate the substrate specificity, the KR domain (BacKR1) was heterologously overexpressed in Escherichia coli. In vitro enzymatic analysis showed that only one of the four diastereomers was formed in the reduction of the racemic (±)-2-methyl-3-oxopentanoyl-N-acetylcysteamine thioester catalyzed by BacKR1. In addition, BacKR1 was revealed to catalyze the reductions of cyclohexanone and p-chloroacetophenone, indicating the potential of KR domians of PKSs as biocatalysts.
Bacterial Proteins ; genetics ; metabolism ; Catalysis ; Cyclohexanones ; metabolism ; Escherichia coli ; enzymology ; Polyketide Synthases ; genetics ; metabolism ; Protein Structure, Tertiary ; Substrate Specificity ; omega-Chloroacetophenone ; metabolism

The purpose of this study is to investigate the effects of multiple-trough sampling design and nonlinear mixed effect modeling (NONMEM) algorithm on the estimation of population and individual pharmacokinetic parameters. Oxcarbazepine and tacrolimus were used as one-compartment and two-compartment model drugs, respectively. Seven sampling designs were investigated using various number of trough concentrations per individual ranging from 1-4. Monte Carlo simulations were performed to produce state-steady trough concentrations. One-compartment model was used to fit simulated data from oxcarbazepine and tacrolimus. The accuracy and precision of the estimated parameters were evaluated using the median prediction error (PE), the median absolute PE and boxplot. The results indicated that trough concentrations could yield reliable estimates of apparent clearance (CL/F). For oxcarbazepine, as the number of trough concentrations per subject increased, the accuracy and precision of CL/F, between-subject variability (BSV) of CL/F and residual variability (RUV) tended to be improved. For tacrolimus, however, although no improvement were observed in the accuracy of CL/F and BSV of CL/F, the PE distribution ranges were significantly narrowed and the RUV estimates were less bias and imprecise. In terms of algorithm, Monte Carlo importance sampling (IMP) and IMP assisted by mode a posteriori estimation (IMPMAP) were consistently better than other methods. Additionally, the sampling design had no significant effects on the individual parameter estimates, which were only depended on the interaction between BSV and RUV in various algorithms. Decreased in BSV and RUV levels can improve the accuracy and precision of the estimation for both population and individual pharmacokinetic parameter estimates.

Objective To develop the quality standard for evaluating Huangdi cataplasm. Methods Thin layer chromatography (TLC) was used to qualitatively identify Astragalus membranaceus (Fisch.) Bunge,Rheum palmatum Linn,Rhizoma Chuanxiong,Angelica sinensis and Resina Draconis in Huangdi cataplasm.HPLC method was used to determine astragaloside A and loureirin B in Huangdi cataplasm. Results The Astragalus membranaceus (Fisch.) Bunge,Rheum palmatum Linn,Rhizoma Chuanxiong,Angelica sinensis and Resina Draconis were well separated by TLC without interference in the negative control.content of Astragaloside A and loureirin B showed good liner relationships with respective peak area within the range of 6.96-23.2 μg,and 0.072-0.648 μg,with r = 0.999 5,r = 0.999 9, respectively;and the average recovery was 97.18%,and 96.93%,RSD was 1.21%(n= 6),1.53% (n = 6 ), respectively. Conclusion The established qualitative and quantitative detection method is simple, specific, reproducible, accurate and reliable, which can be used for quality control of Huangdi cataplasm.

Objective To establish high performance liquid chromatograph ( HPLC ) fingerprint of liqi xiaoying tablets,and to provide reference for quality control of the herbal medication. Methods The chromatography conditions consisted of Aichrom Bond-AQ C18(250 mmí4. 6 mm,5 μm) column with mobile phase of acetonitrile-0. 1% phosphoric acid ( gradient elution) , column temperature of 30 ℃, flow rate of 1 mL · min-1 , injection volume of 20 μL, and UV detection wavelength of 226 nm. Results HPLC fingerprint was established with 13 common peaks,4 of which were identified. The similarity of the HPLC fingerprints of liqi xiaoying tablets from 10 batches was greater than 0. 95. Conclusion The method is accurate, reliable, and can reflect complete information for the quality of liqi xiaoying tablets.