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

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

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.

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.

Objective To observe the protective effect of meicha protein on the heart of spontaneously hypertensive rats(SHR),and explore its mechanism.Methods Fourty healthy SHR rats were randomly divided into 4 groups:model control group,Meicha protein low dose group(70 mg·kg-1)、Meicha protein high dose group(140 mg·kg-1),Compound Kendir Leaves Tablets group(50 mg·kg-1),n=10.The rats were orally administered twice daily by gavage for seven weeks,measuring blood pressure in each group fort nightly.1 h after the last administration,drawing off the blood from carotid,stripping off the heart tissue,and the organ index was calculated;Taking a part of the tissue with 4% paraformaldehyde for Pathological histology.Detection of serum NO,ET-1 levels as well as the organization of the ACE and Ang II mRNA expression to explore the mechanism of its buck.Results Meicha protein could significantly reduce the blood pressure of SHR;The impact on the rat organ coefficient was not obvious,but had a protective effect on heart tissue.Compared with the model control group,the contents of NO an ET-1 were significantly increased(P<0.01).Compared with the model group,the high dose of Meicha protein could induce ACE,AngⅡ,CYP11B2.The expression of mRNA was significantly decreased(P<0.01).Conclusion The possible mechanism of Meicha protein antihypertensionis relevant to increase the content of NO in serum,reduce the content of ET-1 in serum,reduce mRNA expression of ACE and AngⅡin cardiac tissue.

Objective: To study the efficacy,safety and relative characteristics of formulated Chinese medicinal herbs as a vascular embolizing agent. Methods: We prepared a mixture as a vascular embolizing agent from several Chinese medicinal herbs,they served as anticarcinogen and/or coagulant according to the Chinese Pharmacopeia.We studied the characteristics of the mixture through embolizing the hepatic artery in eight pigs with it. Results: The mixture was prepared as a suspension.It was easily injected through catheters and showed good histocompatibility and hemo-compatibility without pyrogenetic response and toxicity.The mixture mainly embolized peripheral arteries,maintaining occlusion for 5 weeks and without formation of collateral circulation.We found injuries of normal hepatic tissues as slight hepatocyte hydrops and focal endochyloma necrosis through optical and electronic microscope. Conclusion: This suspended mixture of Chinese medicinal herbs is safe and effective as a potential peripheral embolizing agent.