Objective To assess the association of tag single nucleotide polymorphisms ( tag SNPs) of SH2B adap-tor protein 3 ( SH2 B3 ) gene with essential hypertension ( EH ) in Han population .Methods Six tag SNPs ( rs7309325 , rs11065898 , rs10849947 , rs2239196 , rs2238154 and rs739496 ) were genotyped in 510 patients with EH and 510 healthy controls using polymerase chain reaction-restriction fragment length polymorphism method ( PCR-RFLP) .Results Compared to CC genotype , the T allele carriers of rs2239196 were more likely to be hy-pertensive ( OR=2.59 ,95%CI 1.36-4.96 ,Bonferroni correction P<0.05 ) .Conclusions The rs2239196 T al-lele is potential a risk factor of EH in Han population .

Objective To study the effect of p38 mitogen activated protein kinase (MAPK) pathway inhibitors SB203580 on cell cycle of K562 cell lines and its mechanisms. Methods The expression of mRNA and protein of p38,Cyclin D2,Cyelin E and P27 in K562 cell lines treated with SB203580 were detected by retrotranscription polymerase chain reaction (RT-PCR) and Western blotting, respectively. Cell cycle was determined by flow eytometry (FCM). Results The expressions of mRNA and protein of p38, Cyclin D2 and Cyclin E in K562 cell lines treated with SB203580 were decreased and the expression of p27 was increased.The percentage of cells in G0/G1 phase was increased and was decreased in S phase. There was a significant difference as compared with K562 cell lines before treated with SB203580. Conclusion SB203580 can affect cell cycle regulatory proteins by p38 pathway and eventually inhibit proliferation of K562 cells.

The present study aimed to explore the effects of Eerdun-Wurile on brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) expressions in the prefrontal cortex of MCAO / R injury rats.Sixty SD male rats of SPF grade were selected to establish the model of MCAO / R with Zea-Longa thread occlusion,and divided into five groups at random:the sham operation group,the model group,the nimodipine group and the Eerdun-Wurile group.After modeling,rats were anesthetized for preparing the brains.The pathomorphological changes of the brains were evaluated by immunohistochemical techniques,such as HE staining and SP.The protein and mRNA expressions of BDNF and NGF in the prefrontal cortex of rats were detected by ELISA and RT-PCR,respectively.As a result,compared with the model group,it was found that the number of necrotic cells in the prefrontal cortex were significantly reduced in the Eerdun-Wurile group (P ＜ 0.05),while the mRNA and protein expressions of BDNF and NGF were significantly increased (P ＜ 0.05).In conclusion,the BDNF and NGF expressions in the prefrontal cortex were up-regulated for stimulating the activation of astrocytes and protecting the neurons with the treatment of Eerdun-Wurile in MCAO / R injured rats,which may be the mechanism of the treatment of Eerdun-Wurile for white vein disease.

Abstract: Objective　The method of "molecular docking - molecular dynamics - in vitro pharmacology" was used to screen and optimize small molecule polypeptide compounds that can block PD-1/PD-L1 binding and have high anti-tumor activity. Methods Using the 5-peptide compound database constructed by our team and the three-dimensional structure data of the PD-L1 protein downloaded from the protein database (PDB), the peptide compounds obtained by flexible molecular docking using Molecular Operating Environment software. The molecular dynamics calculation and analysis of the compounds with the highest GWVI/WSA (generalized Born volume integral/weighted surface area) free energy change value (ΔG) were carried out, including the root mean square deviation (RMSD) of the position change of the weight atom and the interaction energy (the sum of Lennard-Jones potential and Coulombic energy). The blocking effect of ligand compounds on PD-1/PD-L1 binding was analyzed by the homogeneous time-resolved fluorescence (HTRF) technique. The co-culture system of Jurkat T lymphocytes and melanoma B16-F10 cells was established to explore the effect of compound ligands on the killing effect of T cells on tumors and the effect on the secretion level of IL-2 in the co-culture supernatant. Results The selected polypeptide compounds were analyzed by molecular dynamics, and the binding of RGGHA to RGGHH and PD-L1 was stable. There are many kinds of interactions between RGGHA and PD-L1，which can compete with PD-1 ligands to bind Asp122, Try123 and Lys124 sites of the PD-L1 protein and block PD-1/PD-L1 signal transduction. HTRF experiments showed that the binding inhibition rate of RGGHA to PD-1 and PD-L1 was 58.38%, and that of RGGHH was 42.73%. In addition, we established a co-culture system of Jurkat T lymphocytes and melanoma B16-F10 cells to explore the immunostimulatory effect and mechanism of peptides. The results show that RGGHA and RGGHH can significantly increase the secretion level of IL-2, improve the killing ability of T cells against tumor cells and activate the tumor immune microenvironment. Conclusions The study found that the polypeptide compounds RGGHA and RGGHH can effectively block the PD-1/PD-L1 interaction and reactivate the anti-cancer immune response, which can be used as lead compounds for new drug development.

OBJECTIVE：To study the difference of dissolution performance of chemical component and anticonvulsant effect of Bombyx mori decoction and powder taken with water，and to provide reference for the selection of application forms of B. mori. METHODS：The yield of dry extract was determined for decoction and powder biomimetic gastric juice of B. mori. HPLC method was used to detect the content of ammonium oxalate in decoction and powder biomimetic gastric juice of B. mori. The content of protein in decoction and powder biomimetic gastric juice of B. mori was determined with bicinchoninic acid（BCA）method. Mice was divided into normal group（1％Sodium carboxymethylcellulose solution），model group（1％Sodium carboxymethylcellulose solution），positive group （phenytoin，2 mg/kg） and B. mori decoction and powder suspensions high-dose，medium-dose and low-dose groups（0.75，1.5，3 g/kg by crude drug）according to random number table，with 20 mice in each group. After 60 min of intragastric administration，electric stimulation was conducted，and the rate of convulsion in mice was recorded. RESULTS：The yields of dry extract were 22.08％ and 26.40％ in decoction and powder gastric juice of B. mori （P＜0.05）；the contents of ammonium oxalate were 11.22％ and 16.83％ （P＜0.05），and the contents of protein was 3.39％ and 4.92％ （P＜0.01）. Compared with normal group，convulsion rate of mice was increased significantly in model group （P＜0.01）；compared with model group，convulsion rates of mice were decreased significantly in administration groups （P＜0.05 or P＜0.01），and the convulsion rate of mice in B. mori powder suspensions group was lower than decoction group. CONCLUSIONS：The dissolution performance of the chemical component from gastric juice of B. mori powder is better than that of decoction， and the anticonvulsant effect of B. mori powder is better than decoction.

OBJECTIVETo assess the association of tag single nucleotide polymorphisms (tag SNPs) of chymase gene (CMA1) with essential hypertension in Yi population from Yunnan, China.

METHODSA case-control study was carried out. Four tag SNPs(rs1956921, rs1800876, rs5244 and rs1885108) were genotyped in 303 patients with essential hypertension and 312 healthy controls using polymerase chain reaction - restriction fragment length polymorphism(PCR-RFLP) method.

RESULTSNo significant difference in genotypic and allelic distributions of the four polymorphisms was detected between the two groups(P>0.05), and the same results existed in the females. The frequencies of rs1956921 C allele and a C-T haplotype constructed with rs1956921 and rs5244 were greater in male patients compared with male controls(P<0.01).

CONCLUSIONThe rs1956921 C allele of the CMA1 gene and the C-T haplotype constructed with rs1956921 and rs5244 may be risk factors for essential hypertension in ethnic Yi males from Yunnan.

Adult ; Alleles ; Asian Continental Ancestry Group ; ethnology ; genetics ; Blood Pressure ; China ; ethnology ; Chymases ; genetics ; Essential Hypertension ; Female ; Humans ; Hypertension ; ethnology ; genetics ; physiopathology ; Male ; Middle Aged ; Polymorphism, Single Nucleotide

OBJECTIVE:To establish HPLC fingerprint of stir-baked Manis pentadactyla.METHODS:HPLC method was conducted.The determination was performed on Capcell Pak Mg Ⅱ S5 C18 column with mobile phase consisted of acetonitrile-0.1％ phosphoric acid solution (gradient elution) at the flow rate of 0.8 mL/min.The detection wavelength was set at 275 nm,and column temperature was 30 ℃.The sample size was 10 μL.Using oxyphenylaminopropionic acid as reference,HPLC chromatograms of 11 batches of medicinal materials were determined.TCM Chromatogram Fingerprint Similarity Evaluation System (2004 A edition) was used for common peak identification and similarity evaluation.RESULTS:There were 23 common peaks in 11 batches of stir-baked M.pentadactyla,with similarity＞0.90.After validation,HPLC chromatograms of 11 batches of medicinal materials were in good agreement with control fingerprints.CONCLUSIONS:Established HPLC fingerprint can provide reference for the identification and quality evaluation of stir-baked M.pentadactyla.

OBJECTIVE To assess the association of single nucleotide polymorphisms (SNPs) of the T-cadherin (CDH13) gene with metabolic syndrome (MS) among ethnic Han Chinese.METHODS Genotypes of 6 SNPs(rs11646213, rs12596316, rs3865188, rs12444338, rs12051272, and rs7195409) of the CDH13 gene among 453 patients with MS and 526 controls were determined with a TaqMan method, and their association with MS was assessed. RESULTS For 5 SNPs (rs11646213, rs3865188, rs12444338, rs12051272, and rs7195409), no difference was found in allelic and genotypic frequencies of the CDH13 gene between the two groups. Comparing with rs12596316 (AA+GG) genotype, rs12596316 AG genotype has significantly increased the risk of MS(P = 0.01,OR = 1.38,95%CI: 1.07-1.78), though no association was found between particular alleles of the rs12596316 with MS.There was no difference in the frequencies of rs11646213-rs12596316-rs3865188-rs12444338-rs12051272 haplotype between the two groups(P > 0.05). CONCLUSION No association was found between the five SNPs (rs11646213, rs3865188, rs12444338, rs12051272 and rs7195409) of the CDH13 gene with the MS, while the rs12596316AG genotype of the CDH13 gene is associated with the susceptibility to MS among ethnic Han Chinese.