0.05). Conclusion:Administering propofol or midazolam is helpful in avoiding cerebral oxygenation imbalance during CPB.

Acute spinal cord injury can lead to severe motor,sen-sory and sphincter muscle dysfunction.Inflammatory response caused by inflammatory cytokines plays a crucial role in the oc-currence and development of secondary damage.Maintaining the body balance between inflammaion and anti-inflammation through an appropriate anti-inflammatory intervention will be an important strategy for drug therapy of spinal cord injury.This paper mainly introduces the cause,process and participation of inflammatory response in the pathophysiological mechanism of acute spinal cord injury,and also reviews the latest progress of experimental research of anti-inflammatory drugs,aiming to provide reference for finding the safe and effective drugs.

OBJECTIVETo explore the association between C825T polymorphism of G protein beta3 subunit (GNB3) gene and different Hilit types of essential hypertension (EH) in the Uygur nationality of Xinjiang.

METHODSAccording to Uygur medical theories, EH patients (as the EH group) and non-EH patients (as the control group) were assigned to four Hilit groups. The C825T polymorphism of GNB3 was detected in 161 EH patients and 379 non-EH subjects of different Hilit types by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to explore the difference of the genotypes and allelic frequencies and hypertension.

RESULTS(1) In Xinjiang Uygur population, the distribution frequencies of GNB3 C825T polymorphism were in accordance with Hardy-Weinberg (chi2 = 0.871, P = 0.647). (2) There was no statistical difference in the distribution frequencies of three genotypes and two alleles of GNB3 between the EH group and the control group (P > 0.05). (3) There was statistical difference in distribution frequencies of three genotypes between the abnormal Sapra and non-abnormal Sapra group (the sum of abnormal Sewda, abnormal Kan, and abnormal Balhem) (chi2 = 6.905, P = 0.032), especially between the abnormal Sapra and abnormal Balhem groups (chi2 = 10.404, P = 0.006), but there was no statistical difference in distribution frequencies of alleles between the two groups (P > 0.05). (4) In 161 EH patients, there was statistical difference in the distribution frequencies of three genotypes and two alleles between the abnormal Sapra and non-abnormal Sapra group (chi2 = 9.034, P = 0.011; chi2 = 4.701, P = 0.03).

CONCLUSIONSBoth TT genotype and T allele of GNB3 C825T polymorphism might not be associated with EH patients in Xinjiang Uygur populations. However, they were correlated with hypertension patients of non-abnormal Sapra, indicating the pathogeneses of EH with different Hilit types might be different.

Adult ; Aged ; Alleles ; Case-Control Studies ; Essential Hypertension ; Female ; Gene Frequency ; Genotype ; Heterotrimeric GTP-Binding Proteins ; genetics ; Humans ; Hypertension ; classification ; diagnosis ; genetics ; Male ; Medicine, Chinese Traditional ; Middle Aged ; Minority Groups ; Polymorphism, Genetic

Deoxyglycychloxazol (TY501) is a glycyrrhetinic acid derivative which exhibits high anti-inflammatory activity and reduced pseudoaldosteronism compared to glycyrrhetinic acid. In this study, a sensitive and rapid liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was established for the quantitation of TY501 in rat plasma. Plasma samples were treated by precipitating protein with methanol and supernatants were separated by a Symmetry C8 column with the mobile phase consisting of me-thanol and 10 mM ammonium formate (containing 0.1%of formic acid) (90:10, v/v). The selected reaction monitoring (SRM) transitions were performed at m/z 647.4-191.2 for TY501 and m/z 473.3-143.3 for astragaloside aglycone (IS) in the positive ion mode with atmospheric pressure chemical ionization (APCI) source. Calibration curve was linear over the concentration range of 5–5000 ng/mL. The lower limit of quantification was 5 ng/mL. The mean recovery was over 88%. The intra-and inter-day precisions were lower than 6.0% and 12.8%, respectively, and the accuracy was within 71.3%. TY501 was stable under usual storage conditions and handling procedure. The validated method has been successfully applied to a pharmacokinetic study after oral administration of TY501 to rats at a dosage of 10 mg/kg.

In the past two decades,with the increase of smoking population,more and more people are suffering from small cell lung cancer(SCLC).Besides,it is difficult to find an effective way to cure SCLC,since patience can easily develop drug resistance.On the other hand,with the development of science and technology,people began to study the anti-cancer strategy to increase apoptosis,such as inhibiting the overexpression of survival factors.In these survival factors,BCL-2 family has attracted a lot of attention.BH3-only protein is a member of BCL-2 family and it can directly inhibit the expression of BCL-2 protein,thereby prompting apoptosis.Since the BH3-only protein itself is difficult to become a clinical drug, to find alternatives BH3-only protein-BH3 mimetics is particularly important. Plus, more and more researchers have paid attention on the natural BH3 mimetic since it has less side-effect than artificial BH3 mimetics.To find possible BH3 mimetics,we made a primary screening with this pharma-cophore on a small molecular compounds library via Discovery Studio software. And then MTS assay were introduced to verify the activity of compounds. After that, we use Western Blot and Co-IP meth-ods to test the effect of BH3 mimetics.And finally use CDOCKER to predict the further mechanism on autophagy and apoptosis.In our studies, we found 3 possible BH3 mimetics compounds from 170,000 natural small molecular compounds via pharmacophore-based virtual screening.Furthermore,we dem-onstrated AD23,one of the 3 possible natural BH3 mimetics,induced autophagy and apoptosis simulta-neously in dose-time dependence in SCLC cell line. Finally, we use Molecular Docking to predict the further mechanism on autophagy and apoptosis. We believe our works would provide evidences and clues for the structural optimizing and further study of new drugs in the future.

Pancreatic ductal adenocarcinoma (PDAC) is one of the five most malignant cancer. ZX-1201 is one of the active constituents in Alismatis Rhizoma,a well-known traditional Chinese medi-cine with a wide variety of pharmacological properties including diuretic,anti-hyperlipidemic,anti-atheroscle-rotic,anti-cancer,anti-inflammatory and anti-oxidative activities.We investigated the inhibitory effect of ZX-1201 on pancreatic cancer and the relevant molecular mechanism in vitro and in vivo. ZX-1201 inhibited the growth and metastasis of PANC-1 cells in BALB/c nude mice significantly.ZX-1201 inhibited the function of AQP1 via directly interaction and involved in the reversion process of ZX-1201 on TGF-β1. CTGF was an important protein in the reversion process of ZX-1201 on TGF-β1.ZX-1201 inhibited the migration of PANC-1 and CPFAC-1 cells induced by TGF-β1in vitro.ZX-1201 reversed the down-regu-lated of epithelial markers and up-regulated of mesenchymal markers, as well as the up-regulated of Snail and p-Smad2/3 induced by TGF-β1.And ZX-1201 reversed Epithelial-Mesenchymal Transition by down-regulating AQP1 and inhibiting translocation of β-catenin, the promotor of CTGF. According to these,ZX-1201 inhibited the migration of pancreatic cancer cells.We concluded that ZX-1201 inhibited the growth and metastasis of PANC-1 cells in vivo significantly.And AQP1,β-catenin and CTGF were the pivotal proteins in the process of ZX-1201 inhibiting PANC-1 cells migration induced by TGF-β1.

Objective To investigate the expression level of Gas6 in patients with Immune Thrombocytopenia (ITP) and its clinical significance.Methods The experimental group was peripheral blood samples collected from 35 cases diagnosed with ITP in hematology department of Changhai Hospital in Shanghai from October 2013 to December 2015.Control group was peripheral blood from 35 healthy examined individuals at the same time.After separating plasm from the two group samples,the protein level of Gas6,IFN-α,IL-4,IFN-γ and IL-17 were measured by Enzyme-linked immunosorbent assay (ELISA),comparison of expressional level of the two groups was measured by t test.Pearson correlation analysis was used to decide the relation between Gas6 and cytokines such as IFN-α.Results The expression level of Gas6 in experimental and control groups was 27.28±7.56 ng/ml vs 20.51±5.39 ng/ml (t=4.314,P＜0.000 1);IFN-γ was 221.67±57.64 pg/ml vs 45.32 ±16.79 pg/ml (t=17.38,P＜0.000 1);IL-4 was 113.86±26.48 pg/ml vs 49.87±14.98 pg/ml (t=12.44,P＜0.000 1);IL-17 was 168.96±47.88 pg/ml vs 109.56±28.97 pg/ml (t=6.28,P＜0.000 1);IFN-α was 34.83±8.12 pg/ml vs 29.89 ± 5.76 pg/ml (t=2.936,P=0.004 5),all with statistical differences (P＜0.05).Pearson analysis showed that Gas6 was positively related with IL-17,IL-4,IFN γ (r=0.564,0.486,0.449,P＜0.05) and there was difference statistically,but Gas6 was not correlated with IFN-α.Conclusion Gas6 may participate in the disease formation of ITP through affection on cytokines secreted by Th cell subsets,and it was the potential therapeutic and predicted target for this disease clinically.

A rapid, sensitive and simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous determination of clevidipine butyrate and its primary metabolite clevidipine acid in dog blood. After one-step protein precipitation with methanol, the chromatographic separation was carried out on an Ecosil C18 column (150 mm x 4.6 mm, 5 µm) with a gradient mobile phase consisting of methanol and 5 mmol · L(-1) ammonium formate. A chromatographic total run time of 13.0 min was achieved. The quantitation analysis was performed using multiple reaction monitoring (MRM) at the specific ion transitions of m/z 454.1 [M-H]- --> m/z 234.1 for clevidipine butyrate, m/z 354.0 [M-H]- --> m/z 208.0 for clevidipine acid and m/z 256.1 [M-H]- --> m/z 227.1 for elofesalamide (internal standard, IS) in the negative ion mode with electrospray ionization (ESI) source. The linear calibration curves for clevidipine butyrate and clevidipine acid were obtained in the concentration ranges of 0.5-100 ng · mL and 1-200 ng · mL(-1), separately. The lower limit of quantification of clevidipine butyrate and clevidipine acid were 0.5 ng · mL(-1) and 1 ng · mL(-1). The intra and inter-assay precisions were all below 12.9%, the accuracies were all in standard ranges. Stability testing indicated that clevidipine butyrate and clevidipine acid in dog blood with the addition of denaturant methanol was stable under various processing and/or handling conditions. The validated method has been successfully applied to a pharmacokinetic study of clevidipine butyrate injection to 8 healthy Beagle dogs following intravenous infusion at a flow rate of 5 mg · h(-1) for 0.5 h.
Animals ; Butyrates ; blood ; pharmacokinetics ; Calibration ; Chromatography, Liquid ; Dogs ; Infusions, Intravenous ; Pyridines ; blood ; pharmacokinetics ; Tandem Mass Spectrometry

Objective To understand the situation of iodized salt consumption at the household level and non-iodized salt distribution in those areas with low iodized salt coverage.Methods In 2010,iodized salt was monitored in 31 provinces and Xinjiang Production and Construction Corps in accordance with the Monitoring Program of the National Iodine Deficiency Disorders (Trial) (hereinafter referred to as the Program) requirements.Under the jurisdiction of counties (cities,districts,banners) with more than 9 townships (towns,street offices),based on the location of east,west,south,north and center,9 townships (town,district offices) were selected using simple random sampling method; 4 administrative villages (neighborhoods) were selected in each township (town,district office); and 8 residents in each administrative village (neighborhood) were selected.Under the jurisdiction of counties (cities,districts,banners) with less than 9 townships (towns,street offices),based on the location of east,west,south,north and center,1 township(town,district office) was selected using simple random sampling method; 4 administrative villages(neighborhoods) were selected in each township(town,district office);and 15 residents in each administrative village(neighborhood) were selected.Iodized salt coverage rate,qualification rate of iodized salt and consumption rate of qualified iodized salt were calculated in various provinces.The salt samples were tested by semi-quantitative method on the spot and then tested with quantitative method in laboratories.The standard of qualified iodized salt was set as 20-50 mg/kg and that of non-iodized salt was set as ＜ 5 mg/kg (GB/T 13025.7-1999).Results In 2010,a total of 2862 counties(districts,cities and banners) and 14 divisions of Xinjiang Production and Construction Corps,reported the monitoring results,and the monitoring coverage rate was 99.79％(2876/2882).A total of 826 696 copies of edible salt samples were tested,the coverage rate of iodized salt was 98.63％,the consumption rate of qualified iodized salt was 97.95％,and the coverage rate of qualified iodized salt was 96.63％.At province level,only in Tibet iodized salt coverage rate was ＜ 90％.At county level,2755 counties qualified iodized salt coverage rate was ≥90％,and 33 counties iodized salt coverage rate was ＜ 80％.The counties with qualified iodized salt coverage rate of 90％ or more accounted for 96.63％(2785/2882) of the total counties.Conclusions The counties where non-iodized salt coverage is higher than 20％ mainly distributed in the western or coastal areas and adjacent areas with higher iodine.These areas need policy and funding support from governments at all levels to reducc the gap between these areas and other areas.

Objective To investigate the effects of selective cyclooxygenase 2 inhibitor on the hyperplasia of parathyroid glands from uremic rats. Methods Sixty-five 5/6-nephrectomized (Nx) and fifteen sham operated rats were assigned to 4 groups: (1)Sham group (n=14):shamoperated +normal phosphate diet (P 0.8％,Ca 1.2％)； (2) Nx-HP group (n=17):Nx+high phosphate(HP) diet (P 1.2％,Ca 1.2％)； (3)Prophylactic COX2 inhibition group (Prey group,n=18):Nx+HP+celecoxib 100 mg· kg-1·d-1 for 3 months； (4)Therapeutic group (Ther group,n=18):Nx+HP+celecoxib 100 mg·kg-1·d-1 starting at the second month of the 5/6 nephrectomy.At the end of 3 month,blood,urine and parathyroid samples were collected.The expressions of COX2 and PCNA were determined by immunohistochemistry,Western blotting and real-time PCR. Results All of the Nx rats fed with high phosphate diet for 3 months manifested progressively increasing serum creatinine,serum iPTH as well as augmentation of parathyroid gland volume,suggesting that secondary parathyroid hyperplasia animal model was established successfully.Celecoxib significantly decreased serum iPTH levels [Sham (34.77±0.83),Nx-HP(100.73±4.35),Prey (87.36±2.18),Ther (87.47±1.76) ng/L,P＜0.05],the size of the parathyroid glands in Nx rats [Sham (0.461±0.089),Nx-HP (2.436±0.372),Prey (0.987±0.254),Ther (1.27±0.305) mm2/kg,P＜0.05] and PCNA expression in PG determined by Western blotting (decreased to 52.91％ in Prev group and 34.68％ in Ther group respectively,P＜0.05).No significant difference was observed between the two COX2 inhibition groups.The levels of COX2 expression in parathyroid gland were greatly increased in three Nx groups compared with that in sham group (2.47-fold in Nx-HP,2.34-fold in Prey group,3.04-fold in Ther group,P＜0.05).COX2 inhibitor had no effects on COX2 expression in PGs.Real-time PCR analysis demonstrated the same trends of mRNA expression of COX2 and PCNA in PGs of rats. Conclusion Selective inhibition of COX2 may help to suppress the hyperplasia of parathyroid glands in uremic rats.