By using the pharmacophore model of mineralocorticoid receptor antagonists as a starting point, the experiment stud- ies the method of traditional Chinese medicine formula design for anti-hypertensive. Pharmacophore models were generated by 3D-QSAR pharmacophore (Hypogen) program of the DS3.5, based on the training set composed of 33 mineralocorticoid receptor antagonists. The best pharmacophore model consisted of two Hydrogen-bond acceptors, three Hydrophobic and four excluded volumes. Its correlation coefficient of training set and test set, N, and CAI value were 0.9534, 0.6748, 2.878, and 1.119. According to the database screening, 1700 active compounds from 86 source plant were obtained. Because of lacking of available anti-hypertensive medi cation strategy in traditional theory, this article takes advantage of patent retrieval in world traditional medicine patent database, in order to design drug formula. Finally, two formulae was obtained for antihypertensive.
Antihypertensive Agents ; chemistry ; pharmacology ; Databases, Factual ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Medicine, Chinese Traditional ; methods ; Mineralocorticoid Receptor Antagonists ; chemistry ; pharmacology ; Models, Molecular

Objective To study the variation of the pancreatic head arteries and its value in pan- creas transplantation.Methods The DSA data of 300 cases were studied retrospectively:192 cases of celiac trunk angiography,102 cases of superior mesenteric artery angiography,and 6 cases of the com- bined.The distribution and variation of the arteries on the pancreatic head were observed.Results In the celiac angiography cases,typical gastroduodenal artery,superior pancreaticoduodenal artery and its branches were visualized in 73 cases(38%).The posterior superior panereaticoduodenal artery was not anastomosed with the posterior inferior pancraticoduodenal artery in 3 cases.The posterior pancre- aticoduodenal arcade was discontinued in 1 case.The anterior superior pancreaticoduodenal artery, posterior superior pancreaticodoodenal artery,and dorsal pancreatic artery were only distributed across the upper head of the pancreas separately but were not anastomosed each other in 1 case.The variation rate of pancreaticoduodenal arterial arcades was 6.8%(5/73).In 102 cases of the superior mesenteric artery angiography,the inferior pancreaticoduodenal artery was visualized in 42 cases(41%)while its branches were not visualized.In 6 cases of the combined angiography,superior panereaticoduodenal artery was visualized in all of the cases,of which anterior and posterior arcades were visualized in 4 cases(66.7%).The gastroduodenal artery reconstruction was performed in 3 cases of clinical pancre- as transplantation,all of the receivers maintained a normal blood glucose level after transplantation and no surgical complications were found.Conclusions The superior pancreaticoduodenal artery might of- fer more blood supply than inferior pancreaticoduodenal artery in the pancreatic head.The arterial re- construction of the transplanted pancreas should include the gastroduodenal artery because of the pos- sibility of arterial variation on the pancreatic head.

Administration, Inhalation ; Bronchiolitis ; drug therapy ; Bronchodilator Agents ; administration & dosage ; therapeutic use ; Budesonide ; administration & dosage ; therapeutic use ; Female ; Humans ; Infant ; Male ; Poly I-C ; administration & dosage ; therapeutic use

BackgroundIt has been well-known that integrin linked kinase(ILK) plays an important role in the pathogenesis of neorascularization.But there are few researches to elucidate the relationship between ILK and retinal nevascularization. Objective This study was to explore the expression and significance of ILK on retinal neovascularization and new vessels regression in the oxygen-induced retinopathy(OIR) mouse model. Methods One hundred and twenty-eight 7-day-old C57BL/6J mice were randomly divided into the normal group and model group.The mice were rose in(75±2)％O2 environment with mother mice together for 5 days and then in normal environment for 5 days to establish the OIR models.The mice in normal group were rose in the normal environment for 21 days.The 17-day-old mice were sacrificed and retinal sections were prepared for histopathological examination and the numbers of the cellular nuclei of vascular endotheliumbreaking retinalinternal limiting membranewere calculated.Retinal sections and sheeting were prepared in 12,14,17 and 21 -day-old mice to examine the formation and regression of new blood vessel using ADP histochemistry staining,and then immunochemistry,real-time PCR and Western-blotting were used to detect the expressions of ILK and its mRNA in retina. ResultsThe numbers of the cellular nuclei of vascular endothelium breaking retinal internal limiting membrane were (45.64 ± 12.17 )in OIR group,and those of the normal group were( 0.35±0.14 )with a significant difference between two groups (t =22.85,P＜0.05).Retinal new blood vessel appeared in 14-day mice,and peaked in 17-day mice and then regression in 21-day mice.ILK protein was expressed mainly in retinal ganglion cell layer,inner nuclear layer,inner plexiform layer and photoreceptor layer.Real-time PCR showed that ILK mRNA expressing levels in retina in model group were( 1.00±0.22),(1.85±0.17),(1.58±0.43) and(1.53±0.36) respectively in 12-,14-,17- and 21-day mice.Westernblotting determined that the A value of the ILK/β-actin was increased in 12-,14-,17-day mice and decreased in 21-day mice,and the A values were significantly higher in model group than the control group in various aged mice ( t =2.97,P＜0.05 ;t =11.88,P＜0.01 ;t =16.84,P＜0.01 ;t =13.00,P＜0.01 ). ConclusionsThese results indicate a space-time corresponding relation between the expression of ILK and retinal neovascularization.The obvious positive expression of ILK may be highly correlated with retinal neovascularization.

Adipates ; analysis ; Air Pollutants, Occupational ; analysis ; Esters ; analysis ; Gas Chromatography-Mass Spectrometry ; methods ; Phthalic Acids ; analysis ; Workplace

Objective To observe the influence of coal burning fluorosis on learning and memory ability in rats and reveal its possible mechanisms. Methods Healthy 48 SD rats were divided into control, low-fluoride and high-fluoride group. All rats in fluoride exposed groups were fed with the eom polluted by drying processes with burning coal containing high level of fluoride obtained from the endemic fluorosis area to produce the animal model of fluorosis. The experiment period were 3,6 mouths, respectively. The ability of leaning and memory was measured by Morris test and cholinesterase activity detected by photometric method at 3 or 6 month after experiment, respectively. Results Fluoride contents signifieantlly influenced the escape latency, the numbers of crossing the platforms and the time of staying the platforms(the value of F was 29.29,6.47,6.50, respectively, P<0.01).In addition, the numbers of crossing the platforms and the time of staying the platforms were influenced by the exposed time(the value of F was 16.11,45.59, P<0.01). Furthermore, the fluoride contents and the exposed time had an interaction between the numbers of crossing the platforms and the time of staying the platforms (the value of F was 4.67,5.68, P<0.05 or<0.01). Three months after the experiment, the mean values of escape latency [(14.71± 4.85)s] of rats in highly fluoride exposed group were significantly prolonged as compared with controls [(9.28±4.22)s]; 6 month after the experiment, the mean values of escape latency[(12.42±8.03)s, (17.48± 8.05)s] of rats in both groups exposed to fluoride were significantly prolonged as compared to controls [(7.04± 3.29)s, P<0.05]. The decreased numbers of crossing the platforms[(1.62±0.87)number] and the declined time of staying the platforms[(16.70±5.02)s] were found in the rats exposed to high fluoride as compared to controls [(3.53±1.67 )number, (23.33±5.35)s, P<0.05]. The fluoride contents obviously influenced the activities of acetylcholinesterase and butylcolinesterase (the value of F was 12.83,13.27, P<0.01). On the other hand, the times of breeding also influnced the activities of butylcolinesterase (the value of F was 16.26, P<0.01). In 3 months of the experiment, the activities of butylcolinesterase [(0.55±0.12)kU/g] in low fluoride exposed group were significantly decreased in comparison with controls[(0.73±0.10)kU/g, P<0.05]. The activities of acetylcholinesterase[(0.62±0.42)kU/g] and butylcolioesterase[(0.58±0.10)kU/g] in high fluoride group were significantly decreased as compared to eontrois[(1.41±0.52), (0.73±0.10)kU/g, P<0.05]. The correlation analysis showed that there was a negative correlation between the cholinesterase and the escape latency(r=-0.68, P< 0.01), and a positive correlation between the cholinesterase and the time of staying the platforms(r=0.57, P< 0.01). Conclusions The ability of learning and memory in rats with coal buring fluorosis was decreased, which might be connected to the decreased activity of cholinesterase in a dose-effect correlation.

(3S)-Linalool synthase (LIS) is a key enzyme involved in the monoterpene biosynthetic pathway. Based on our previous transcriptome study, the expression level of LIS gene was exceedingly related to glycyrrhizic acid (GA) biosynthesis. Therefore, we used hairy root culturing to further investigate the effect of LIS on the GA biosynthesis. A LIS gene (GenBank accession number: MZ169552) was cloned from Glycyrrhiza uralensis. The plant binary overexpression vector pCA-LIS was constructed by gene fusion. G. uralensis hairy roots overexpressing LIS were induced by the Agrobacterium rhizogenes ATCC15834. The expression levels of LIS were analyzed by real-time quantitative PCR (RT-qPCR) and the contents of GA in hairy root lines were determined by UPLC. It was found that in the hairy root lines overexpressing LIS, the expression levels of LIS were significantly higher than that in the wild type, while the contents of GA were remarkably lower than those in the wild type and negative control. These findings indicate that the expression level of LIS is negatively correlated with the accumulation of GA. In this study, LIS was cloned from G. uralensis for the first time and the negative regulatory effect of LIS on GA biosynthesis was confirmed by reverse genetics. This work provides support for further improvement of the molecular regulatory network of GA biosynthesis in G. uralensis.

Objective To evaluate the security of big animals with a new bioartificial liver system .Methods Six Tibet pigs re-spectively received treatment of hybrid artificial liver and simple bioartificial liver ,observed and recorded the vital signs ,venous pressure ,transmembrane pressure and slurry pot pressure each hour ,and collected blood to make endotoxin and bacterial culture test in the zero hour ,fourth and eighth hour .Results Compared with the zero hour ,venous pressure ,transmembrane pressure ,slur-ry pot pressure were much higher in the fifth hour (P< 0 .05) ,and there were no significant difference in the rest of other time points(P>0 .05) .The mean arterial pressure and respiratory rate in all time point showed no significant changes (P>0 .05) .Com-pared with the zero hour ,the heart rate was much lower in the second hour (P<0 .01) .The values of blood endotoxin were less than 0 .5 EU/mL in the zero hour ,fourth and eighth hour from beginning ,and the bacterial culture test showed no growth of bacteria . Conclusion The experiment of big animals with a new bioartificial liver system was safe ,the efficacy in the treatment of hepatic failure could be assessed further .

OBJECTIVE:To evaluate the curative effect and safety of reduced glutathione for injection(Atomolan) on the Alcoholic Liver Disease(ALD).METHODS:This was a randomized,placebo controlled study,in which the reduced glutathione for injection(Gluthion) was used as control substance.A total of 261 ALD patients were randomly divided into 2 groups in 1:1 ratio(trial group,n=135;control group,n=126).The dosage,route and course of treatment in two groups were the same.Clinical data including biochemical parameters,symptoms and signs in two groups were monitored.RESULTS:The excellent effective rate,effect rate and total effective rate in the trial group were 58.5%,23.7% and 82.2%,respectively,those in the control group were 57.9%,22.2% and 80.2%,respectively,showing no significant difference between the 2 groups(P=0.90).CONC-LUSION:The study showed that the domestic glutathione for injection had a sound efficacy in improving clinical symptoms and recovery of liver biochemical parameters,showing equivalent efficacy to the control preparation good safety.

Objective To prepare a innovative VP3 gene‐loaded ultrasound microbubble decorated with TATp and SDF‐1 , having the extracellular accumulation and intracellular permeation function ,and characterize their property .Methods VP3 gene‐loaded ultrasound microbubbles were prepared with the method of W/O/W double emulsion .SDF‐1 and TATp were covalently con‐gjugated to the surface of poly‐lactic/acid‐glycolic acid(PLGA) microbubble though thioether bonds to prepare gene‐loaded targeted ultrasound mirobubbles .Their particle size ,distribution and surface potential were determined by Malvern measuring instrument . The conjugation status of TATp and SDF‐1 were evaluated by flow cytometry and confocal microscopy .Their DNA protection were identified by digestion reaction test .The vitro targeting capacity was preliminarily assessed by light microscopy and flow cytometry , and the vitro ultrasound imaging was investigated under high frequency imaging condition .Results The gene‐loaded targeted ultra‐sound mirobubbles showed regularly sphericity .The diameter was (536 .00 ± 16 .55)nm ,and showed a narrow distribution .The zeta potential was(-0 .08 ± 0 .08)mV .The average gene loading was 0 .62% ,with the average rate of 36 .13% gene encapsulation effi‐ciency .The DNA protective effect sustained 60 min without damage .Connection rate of TATp and SDF‐1 coupled with PLGA mi‐crobubbles surface was 69 .84% .The vitro targeting study showed that more targeted microbubbles stably clustered together in the tongue SCC‐15 cell membranes with the connection rate of 91 .44% ,while non‐targeted microbubbles combination rate was 12 .96% .Moreover ,the vitro ultrasound imaging was tiny dot ,even high echo .Conclusion TATp‐SDF‐1‐VP3‐PEG‐PLGA micro‐bubbles were prepared successfully ,which can efficiently target to tongue SCC‐15 cells ,and pass through the cell membranes at a short time in company with outstanding ultrasound imagings in vitro .