Objective:To investigate the mechanism of therapeutic effects of Rhein on insulin resistance from aspects of the expression of resistin mRNA and plasma free fatty acid(FFA) in diabetic obese rats.Methods:The streptozotocin(STZ) and high fat diet-induced diabetic obese rats were divided into three groups at random.They were differently treated with Rhein,pioglitazone and saline by gavage.The expressions of resistin mRNA,plasma free fatty acid(FFA),as well as blood lipid in all groups were detected after administration by gavage for 8 weeks.Results:Similar to pioglitazone,Rhein can reduce the expression of resistin mRNA and the level of FFA,TC,TG and LDL(P

0.05), meanwhile,after being treated with higher-dose Huangkui Capsule,there were no significant differences for theophylline pharmacokinetics in rats,but AUC_(0-24 h) of chlorzoxazone after treatment was 1.75 times larger than that before treatment(P

AIM:To research the absorption mechanism of aesculin across Caco-2 monolayer model.METHODS:The Caco-2 cell monolayers drug transport model was assigned to study the double transport mechanism of aesculin to explore the absorption of aesculin according as time and drug concentration determined through HPLC and the P_ app was calcalated.RESULTS:In the Caco-2 monolayer model,the transport of aesculin form Apical to Basolateral was similar to the transport form basolateral to apical.CONCLUSION:The main mechanism of the aesculin intestinal absorption in the Caco-2 monolayer model is passive transference.

0.05).Conclusion When given concomitantly as a Cocktail,theophylline,chlorzoxazone and dapsone have no pharmacokinetic interaction,which could be used together to evaluate CYP1A2,CYP2E1 and CYP3A4 activity.

Objective: : To explore the effect of PD-1 gene knockout by CRISPR/Cas9 system on the proliferation and IFN-γ secretion in human T cells. Methods: : The sequence of sgRNA targeting PD-1 was designed. The PD-1-sgRNA and Cas9 mRNA were synthesized by T7 RNApolymerase in vitro, and then the mixture of PD-1-sgRNAand Cas9 mRNAwas delivered into activated T cells by nucleofection. The efficiency of gene knockout was confirmed by sequencing. The phenotypes of T lymphocytes and the expression of PD-1 after gene knockout were analyzed by Flow cytometry. The proliferation of T lymphocytes was calculated by trypan blue counting. The level of IFN-γ secreted by T lymphocytes was detected by ELISA. Results： ：PD-1-sgRNA and Cas9 mRNA were successfully synthesized in vitro and delivered into T cells by nucleofection. Sequencing technology confirmed that the PD-1 gene sequence was edited and the editing efficiency was 58.3%. The expression of PD-1 on T lymphocyte surface was down-regulated successfully by CRISPR/Cas9 system [(9.6±1.85)% vs (16.2±2.05)%, P<0.05]. The knockout of PD-1 gene did not affect the proliferation and phenotype of T lymphocytes(P<0.05); However, compared with the control group, the level of IFN-γ secreted by T lymphocytes in the PD-1sgRNA group was significantly increased (P<0.01). Conclusion: : CRISPR/Cas9 system can successfully ablate PD-1 gene in human T lymphocytes, which could block the negative regulation of PD-1／PD-L1 and further promote the IFN-γ secretion in T cells.

AIM: To investigate the effects of Tangmoning (TMN) Granule on nerve conduction velocity, red blood cell sorbitol (RBC S) level in diabetic rats and probe the mechanism of prevention and treatment of diabetic peripheral neuropathy. METHODS: The model of diabetic rat was induced by strepotozotocin. The animals were randomly divided into six groups:TMN minimal dose group, TMN mild moderate dose group, TMN maximal dose group, methycobal group, model group and normal control group. All TMN groups were treated with TMN Granule through tube feeding (2.95 g/kg、5.90g/kg、11.80g/kg). Methycobal group was treated with methycobal tablets through tube feeding (0.14mg/kg). The duration of treatment was 3 weeks. The caudal nerve conduction velocity, RBC S content were investigated before and after treatment. RESULTS: It showed that TMN Granule could increase the caudal nerve conduction velocity significantly in the maximal dose group and the mild moderate dose gorup ( P

Aim To establish an UPLC-ESI-MS method for determination of asiaticoside and investigate its application to pharmacokinetic study in rats.Methods Eight rats were given 40 mg·kg~(-1) asiaticoside iv respectively.Drug plasma concentration was determined by UPLC-ESI-MS.Pharmacokinetic parameters were evaluated.Results Calibration curves were linear over 0.038～7.6 mg·L~(-1) and LLOQ was 38 μg·L~(-1),the recoveries of asiaticoside from plasma were larger than 95%,and RSD of inter-day and intra-day assay were below 10%.After iv administration of 40 mg·kg~(-1) asiaticoside,the pharmacokinetic parameters of AUC(0-t),T(1)/(2)β,CL,Vd were (81 443.67±57 156.81) μg·L~(-1)·min~(-1),(23.44±9.60) min,(0.19±0.07) L·min~(-1)·kg~(-1),(8.92±6.68) L·kg~(-1),respectively.Conclusion The method described in this report was sensitive and specific,and suitable for pharmacokinetic studies of asiaticoside in rats.

This article analyzed the difference between Chinese and Russian traditional medical treatments from the part of herbs,acupuncture/acupressure therapy,manual therapy,psychotherapy,and sports.TCM had a separate comprehensive diagnosis and treatment system,Russia traditional medicine,attached to Western medicine,had not formed the independent diagnostic and treatment system.

A liquid chromatography-quadrupole-time-of-flight mass spectrometer(LC-Q/TOF-MS) based urinary metabolomic approach was employed to assess the toxicity-alleviation effect of Huangqi oral solution(HOs) on cisplatin-exposed rats and explore its possible mechanisms. Rat toxicity model was developed by multiple intraperitoneal injection of low-dose cisplatin, while HOs was orally administrated to rats simultaneously for 16 consecutive days to attenuate or reduce the cisplatin-induced toxicity. 24-hour urine samples on day 18 were collected and analyzed using LC-Q/TOF-MS to obtain the dataset of urinary metabolites. Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were employed to assess the quality of the dataset and screen the potential toxicity-alleviation biomarkers. The serum level of rat creatinine and urea nitrogen on day 20 was determined, and the results showed that successive administration of HOs significantly reduced the cisplatin-induced increase of creatinine and urea nitrogen. PCA cluster analysis clearly demonstrated that HOs could partly improve the CDDP-induced abnormality of metabolic profiling. 35 urinary metabolites were finally screened as the potential biomarkers associated with the toxicity-attenuation effect of HOs, according to the combination of the analysis results of OPLS-DA, t-test and fold change analysis. Further metabolic pathway analysis revealed that HOs could restore the metabolic disorders of amino acid, energy and nucleotide, thereby exerted its toxicity-alleviation effect.

BACKGROUND:In view of the unavoidable problems of autogenous and al ogenous bone grafts, it is an urgent need to develop biodegradable bone substitute materials, among which is calcium phosphate material that has become a hot spot in the domestic and foreign research. OBJECTIVE:To develop a biodegradable calcium phosphate material for bone repair based on tetracalcium phosphate (TTCP). METHODS:The biodegradable calcium phosphate cement made from TTCP, dicalcium phosphate anhydrous and different constituents of curing liquids was prepared under room temperature (about 25 ℃). The effects of solid components, liquid components as well as calcinations and drying temperature on the physical and biological performances were detected through X-ray diffraction test, hardness test, decay in a simulated body fluid, hemolysis and cytotoxicity tests, respectively, to select the bone repair material with excel ent performances. RESULTS AND CONCLUSION:When the calcination temperature was lower than 1300 ℃, TTCP was rarely available;only close to 1400 ℃, the relatively pure TTCP was gained. A large number of pure TTCP were gained by rapid cooling because of avoidance of the moisture impact, but slow cooling made the main products to be hydroxyapatite, suggesting that rapid cooling is essential to obtain pure TTCP. With the increase of the proportion of citric acid solution in the liquid phase, the pH values and the hemolysis rate in the bone cement soak solution were increased gradually, illustrating that citric acid solution is easy to induce hemolysis. In vitro cel experiments showed that the hemolysis rate of bone cement with a solution of 2:1 NH4/Na ratio was the lowest, and the biocompatibility was the best, which was the most favorable to cel growth. Cements was made of calcined powders sieved at 1400 ℃ and showed the shortest initial setting time, least effect on pH values, lowest disintegration rate and hemolysis rate, and slightest inhibition effect on the cel proliferation, indicating that the bone cements made of sieved powder after 1400 ℃ calcination is more suitable for clinical application.