The inter-species differences of thienorphine metabolism were investigated in human, Beagle dog and rat liver microsomes, by comparing enzyme kinetics of the parent drug and the formation of its major metabolites. The incubation systems of thienorphine with liver microsomes of the three species were optimized in terms of thienorphine concentration, microsomal protein content and incubation time. The concentrations of thienorphine and its metabolites in incubates were measured by a LC-MS/MS method. The biotransformation of thienorphine by human liver microsomes was the lowest among the three species. The K(m), V(max), CL(int) and T1/2 of thienorphine obtained from human liver microsomes were (4.00 +/- 0.59) micromol x L(-1), (0.21 +/- 0.06) micromol x L(-1) x min(-1), (117 +/- 3.19) mL x min(-1) x kg(-1) and (223 +/- 6.10) min, respectively. The corresponding kinetic parameters for dog and rat liver microsomes were (3.57 +/- 0.69) and (3.28 +/- 0.50) micromol x L(-1), (0.18 +/- 0.04) and (0.14 +/- 0.04) micromol x L(-1) x min(-1), (213 +/- 1.06) and (527 +/- 7.79) mL x min(-1) x kg(-1), (244 +/- 1.21) and (70.7 +/- 1.05) min, respectively. A total of six phase I metabolites were observed in liver microsomes, including one N-dealkylated metabolite, three oxidative metabolites and two N-dealkylated oxidation metabolites. All these six metabolites were detected in the liver microsomes of the three species. However, the relative amounts of the metabolites generated were different in three species. The results indicated that the major phase I metabolic pathway of thienorphine was similar in the liver microsomes from all three species. However, the inter-species differences observed were relative amounts of the metabolites as well as the metabolic characteristics of thienorphine in liver microsomal incubates.

The inter-species differences of thienorphine metabolism were investigated in human, Beagle dog and rat liver microsomes, by comparing enzyme kinetics of the parent drug and the formation of its major metabolites. The incubation systems of thienorphine with liver microsomes of the three species were optimized in terms of thienorphine concentration, microsomal protein content and incubation time. The concentrations of thienorphine and its metabolites in incubates were measured by a LC-MS/MS method. The biotransformation of thienorphine by human liver microsomes was the lowest among the three species. The Km, Vmax, CLint and T1/2 of thienorphine obtained from human liver microsomes were (4.00 ? 0.59) ?mol?L-1, (0.21 ? 0.06) ?mol?L-1?min-1, (117 ? 3.19) mL?min-1?kg-1 and (223 ? 6.10) min, respectively. The corresponding kinetic parameters for dog and rat liver microsomes were (3.57 ? 0.69) and (3.28 ? 0.50) ?mol?L-1, (0.18 ? 0.04) and (0.14 ? 0.04) ?mol?L-1?min-1, (213 ? 1.06) and (527 ? 7.79) mL?min-1?kg-1, (244 ? 1.21) and (70.7 ? 1.05) min, respectively. A total of six phase I metabolites were observed in liver microsomes, including one N-dealkylated metabolite, three oxidative metabolites and two N-dealkylated oxidation metabolites. All these six metabolites were detected in the liver microsomes of the three species. However, the relative amounts of the metabolites generated were different in three species. The results indicated that the major phase I metabolic pathway of thienorphine was similar in the liver microsomes from all three species. However, the inter-species differencesobserved were relative amounts of the metabolites as well as the metabolic characteristics of thienorphine in liver microsomal incubates.

Serum 25-(OH)D3concentration was determined in subjects with different types of obesity. The serum 25-(OH)D3levels in overweight or obese and central obese subjects were lower than that in non-obese subjects.(P＜0.01). In a multiple linear regression analysis serum 25-(OH)D3was independently and negatively correlated with body mass index and waist circumference.

Objective To evaluate the association of body weight with brachial-ankle pulse wave velocity (baPWV) in females.Methods A total of 2 921 residents (≥20 years old) were selected by the stratified cluster random sampling method from March to December 2011.Arterial stiffness was assessed by baPWV.Multivariate logistic regression analysis was used to evaluate the effect of body mass index (BMI) on arteriosclerosis.The predictive value of BMI to evaluate arteriosclerosis was analyzed by using receiver operation characteristic (ROC) curve.Results The prevalence of arteriosclerosis was significantly increased in overweight/obese residents (P＜0.01).BMI was positively correlated with baPWV (r=0.310,P＜0.01).The prevalence of increased arterial stiffness in individuals≥65 years older was higher than that in people of 20-40 or 41-64 years old (x2 values were 677.30 and 347.26,respectively; both P＜0.01).For females of 20-40 or 41-46 years old,the prevalences of increased arterial stiffness in overweight and obese groups were higher than those in normal body weight group (both P＜0.01).In univariate analysis,age,resting heart rate,systolic blood pressure (SBP) and diastolic blood pressure (DBP) were correlated with arteriosclerosis (all P＜0.01).The odds ratio for the prevalence of arteriosclerosis in overweight women was 2.017 (95％ confidence interval (CI):1.637-2.486,P＜0.01) and that in obese women was 2.759 (95％ CI:1.964-3.876,P＜0.01) after adjustment for age,resting heart rate and blood pressure.The area under the ROC curve was 0.693 (95％ CI:0.671-0.715,P＜0.01) to evaluate arteriosclerosis in females and the optimal cut-off point for BMI was 23.42 kg/m2.Conclusions For females,overweight and obesity may be risk factors of arteriosclerosis.The optimal cut-off point for BMI to evaluate arteriosclerosis in women could be 23.42 kg/m2.

Refractory wounds are the common complication of diabetes,and the therapeutic scheme and methods are paid more and more attention nowadays. The influence of traditional Chinese medicines on diabetic wound healing, such as promoting fibroblasts proliferation, enhancing granulation tissue formation, increasing the secretion of growth factors and reducing the wound scar, was re-viewed in the paper to provide scientific basis and reference for traditional Chinese medicines used in diabetic refractory wounds.

The biotransformation, CYP reaction phenotyping, the impact of CYP inhibitors and enzyme kinetics of 3-cyanomethyl-4-methyl-DCK (CMDCK), a new anti-HIV preclinical candidate belonging to DCK analogs, were investigated in human intestinal microsomes and recombinant cytochrome P450 (CYP) enzymes. CMDCK (4 micromol L(-1)) was incubated with a panel of rCYP enzymes (CYP1A2, 2C9, 2C19, 2D6 and 3A4) in vitro. The remaining parent drug in incubates was quantitatively analyzed by a LC-MS method. CYP3A4 was identified as the principal CYP isoenzyme responsible for its metabolism in intestinal microsomes. The major metabolic pathway of CMDCK was oxidation and a number of oxidative metabolites were screened with LC-MS. The Km, Vmax, CLint and T1/2 of CMDCK obtained from human intestinal microsome were 45.6 micromol L(-1), 0.33 micromol L(-1) min(-1), 12.1 mL min(-1) kg(-1) and 25.7 min, respectively. Intestinal clearance of CMDCK was estimated from in vitro data to be 3.3 mL min(-1) kg(-1), and was almost equal to the intestinal blood flow rate (4.6 mL min(-1) kg(-1)). The selective CYP3A4 inhibitors, ketoconazole, troleandomycin and ritonavir demonstrated significant inhibitory effects on CMDCK intestinal metabolism, which suggested that co-administration of CMDCK with potent CYP3A inhibitors, such as ritonavir, might decrease its intestinal metabolic clearance and subsequently improve its bioavailability in body.

Objective To develop a small-diameter tissue-engineered blood vessels which possesses normal blood vessels physiological structure, good biocompatibility, and mechanical properties. And it was evaluated by mechanical and biological of national standard of medi-cal transfusion material. Methods The bio-derived material were regarded as the ground substance, and it was evaluated by mechanical and biological of national standard after composite modification. Results The axial and radial tensile stress of the blood vessel was 23. 14 N and 36. 79 N respectively, and it was greater than the standard 7. 5N. The tensile rate of the axial and radial was 95. 19% and 80. 24% respec-tively, which were higher than the standard value 20%. The suture strength of the blood vessel was 13. 71 N, which was conform to the me-chanical requirement. Mainly used blood vessels or its extracts to detect the pH of the blood vessels is in the scope of control deionized water pH (7. 5 ± 1. 5);the hemolysis rate was 1. 3972% which was less than 5%;the whole blood coagulation time was 50% longer than the con-trol level, and there was no stimulation after intradermal injection. Conclusion With bio-derived material as the ground substance and com-positely modified, this kind od blood vessels is conform to the mechanical and biological of national standard, and it has the potential of clini-cal application which could play an important role in the replacement therapy of small-diameter vascular xenografts.

The incidence of nonalcoholic fatty liver disease (NAFLD) has been increasing in China year by year, and NAFLD has become the second most common liver disease after viral hepatitis. Its development is closely associated with insulin resistance and oxidative stress and NAFLD is one of the important components of metabolic syndrome. Ghrelin is a newly discovered endogenous ligand for growth hormone secretagogue and has broad biological functions. Ghrelin not only affects the metabolic process of glucose and lipids, but also plays an important role in the development and progression of NAFLD. In this review, the role of endogenous Ghrelin expression in the development and progression of NAFLD is briefly summarized and the Ghrelin regulation in the development and progression of NAFLD is pointed out, which will provide new approaches to the clinical treatment of NAFLD.

Objective To explore a new efficient extraction method of dorsal root ganglions(DRGs)of rats by exploring and extracting DRGs reversely along the nerve traveling pathway. Methods The DRGs were extracted by the traditional method of opening the intervertebral foramina and the new method, extracting DRGs reversely along the nerve traveling pathway,respectively. The time consuming and the number of intact DRGs obtained with these two method were compared. Results The number of intact DRGs(L3-5segments,both sides)extracted from each rat with the traditional method was(3.08 ± 1.31),and the average time consuming of each DRG was(5.58 ± 1.21)min. As for the new method ,the number of intact DRGs extracted from each rat was(4.29 ± 1.08), and the average time consuming was(1.69 ± 0.91)min,significantly better than that of the traditional method(P < 0.05 for both). Conclusions The new method of exploring and extracting DRGs reversely along the nerve traveling pathway is more efficient for obtaining intact DRGs of rats,providing more useful tissue materials for subsequent culture and morphological studies of DRG cells.

Objective:To explore the relationship between the preoperative fear of pain(FOP) and postoperative pain in patients with lung cancer undergoing video-assisted thoracoscopic surgery, with a view to provide a basis for psychological and behavioral intervention in perioperative pain.Methods:One hundred lung cancer patients underwent thoracoscopic surgery from August 2018 to December 2019 were recruited. The FOP was collected by the Chinese version of the fear of pain questionnaire-Ⅲ before operation. And postoperative pain including rest pain and cough pain was collected after surgery. The correlation analysis and relative risk coefficient was used to evaluate the relationship between preoperative FOP and postoperative pain.Results:Both rest pain and cough pain were positively correlated with FOP with the correlation coefficients of 0.404 and 0.489 (both P <0.05). Patients with a high level of FOP before surgery were more likely to report severe pain when coughing after surgery, which was 3.643 times (95% CI value was 1.585-8.372) higher than the patients with non-high level preoperative FOP. Conclusions:Patients with a high level preoperative FOP may report higher pain after surgery. Screening and identification of such patients are needed for further cognitive behavioral intervention.