To study the quantitative structure-activity relationship (QSAR) between the stuctures of 29 flavonoids and the inhibitory activity of their multidrug resistance-associated protein (MRP) 1 and 2 by using the comparative molecular similarity index analysis (CoMSIA). By studying the impact of the combination of different molecular force fields, researchers obtained the molecular force fields that played an important role in inhibiting the activity of MRP1 and MRP2, built the optimized QSAR model, and discussed the structural modification method for flavonoids' multidrug resistance-associated protein inhibitor. The results of the study could not only provide the guidance for new drug R&D, but also help partially discuss the synergy mechanism between MRP1 and MRP2 receptors and traditional Chinese medicines containing flavonoids.
Drugs, Chinese Herbal ; chemistry ; pharmacology ; Flavonoids ; chemistry ; pharmacology ; Humans ; Models, Molecular ; Multidrug Resistance-Associated Proteins ; antagonists & inhibitors ; chemistry ; Quantitative Structure-Activity Relationship

Animals ; Cardiovascular System ; chemistry ; Female ; Group II Phospholipases A2 ; blood ; Group IV Phospholipases A2 ; blood ; Group V Phospholipases A2 ; blood ; Group X Phospholipases A2 ; blood ; Male ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar

Objective To investigate the clinical features and risk factors of primary Sjogren's syndrome (pSS) patients with malignancies.Methods The clinical features of 29 pSS patients with malignancies from January 1985 to March 2008 were retrospectively analyzed.Results The ratio of pSS with malignancies to all hospitalized pSS patients from January 1985 to March 2008 was 2.2%.In these patients,8 were lymphoma,4 were breast cancers,2 were myeloma,2 were thymoma,2 were lung cancer,2 were gastric carcinoma,2 were hepatoma,2 were colon carcinoma and 2 were tongue cancer.Uterine cervix cancer,renal carcinoma,thyroid carcinoma and carcinoma of parotid gland each were fund in this series of patients.Conclusion The most common malignancy in pSS is lymphoma and the major of pathological type is B cell non-Hodgkin's lymphoma.

Objective To detect anti-M3 receptor antibodies in primary Sj(o)gren's syndrome(pSS)patients and to explore its association with clinical manifestations.Methods Anti-M3 antibodies were tested in 70 patients with pSS,50 patients with systemic lupus erythematosus(SLE)and 76 normal controls with ELISA and Western blot.The correlation between anti-M3 antibodies and other clinical manifestations was analyzed.Results (1)The positive rate of anti-M3 antibodies in pSS Was 47.14% using ELISA and 60.00% using Western blot in SLE 4.00% using ELISA and 12.00% using Western blot and in normal controls 14.47% using ELISA and 15.79% using Western blot.(2)The incidence of sehirmer test,tear break-up time(BUT),whole saliva flow rate,punctate epithelial erosions(PEE)on the corneas and external eye examination were not significantly different between the anti-M3 positive and negative groups.(3)The incidences of IgG,rheumatoid factor,SSB and fluorescence index(FI)＞3 were higher in the positive group than in the negative group using EUSA.Conclusion The positive rate of anti-M3 antibodies is higher in pSS than in SLE and normal controls and in some degree it has correlation with the lesion in salivary gland.

OBJECTIVEThe aim of the study was to detect the expression of Ki67 and P53 proteins in the gingival tissue before and after wearing three kinds of dental casting alloy crowns.

METHODSThe three kinds of dental casting alloys (58% golden alloy, NiCr alloy, NiCr alloy excluding Be) were used to make full crowns for 3 dogs in each group. Another 3 dogs were taken as control. The immunohistochemistry Envision method was used to measure the expression of Ki67 and P53 proteins in the gingival tissue before wearing the crowns, 2 weeks, 1 month, 2 months, 3 months after wearing the crowns.

RESULTSThe expression of Ki67 and P53 proteins in gingival tissue increased 1 month after wearing NiCr alloy and NiCr alloy excluding Be, then decreased gradually. And the expression of Ki67 and P53 proteins in 58% golden alloy group was similar to that in control. No pathological change was observed in all samples.

CONCLUSIONTwo kinds of NiCr alloy crowns both can increase the expression of Ki67 and P53 proteins in gingival tissue, but 58% golden alloy crowns can not. So compared with NiCr alloy crowns, 58% golden alloy crowns have better biological properties. And none of three kinds of dental alloy crowns may induce long-term abnormal proliferation in gingival tissue.

The combined application of statins that inhibit HMG-CoA reductase and fibrates that activate PPAR-α can produce a better lipid-lowering effect than the simple application, but with stronger adverse reactions at the same time. In the treatment of hyperlipidemia, the combined administration of TCMs and HMG-CoA reductase inhibitor in treating hyperlipidemia shows stable efficacy and less adverse reactions, and provides a new option for the combined application of drugs. In this article, the pharmacophore technology was used to search chemical components of TCMs, trace their source herbs, and determine the potential common TCMs that could activate PPAR-α. Because there is no hyperlipidemia-related medication reference in modern TCM classics, to ensure the high safety and efficacy of all selected TCMs, we selected TCMs that are proved to be combined with statins in the World Traditional/Natural Medicine Patent Database, analyzed corresponding drugs in pharmacophore results based on that, and finally obtained common TCMs that can be applied in PPAR-α and combined with statins. Specifically, the pharmacophore model was based on eight receptor-ligand complexes of PPAR-α. The Receptor-Ligand Pharmacophore Generation module in the DS program was used to build the model, optimize with the Screen Library module, and get the best sub-pharmacophore, which consisted of two hydrogen bond acceptor, three hydrophobic groups and 19 excluded volumes, with the identification effectiveness index value N of 2. 82 and the comprehensive evaluation index CAI value of 1. 84. The model was used to screen the TCMD database, hit 5,235 kinds of chemical components and 1 193 natural animals and plants, and finally determine 62 TCMs. Through patent retrieval, we found 38 TCMs; After comparing with the virtual screening results, we finally got seven TCMs.
Acyl Coenzyme A ; metabolism ; Animals ; Databases, Factual ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Hydrophobic and Hydrophilic Interactions ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; chemistry ; pharmacology ; Lipid Metabolism ; drug effects ; Lipids ; blood ; Medicine, Chinese Traditional ; Models, Molecular ; Quantitative Structure-Activity Relationship ; Technology

0.05).At different time points after ischemia-reperfusion,the expression of cytochrome C and activation of caspase-3 were lower in the transgen mice than that in the wild type rats.Conclusions Under standard condition,overexpression of bcl-xl could significantly reduce the infarct area and improve neurological function in transgene mice than those in the wild type rats.The effect of overexpression of bcl-xl might be realized through inhibiting the apoptosis of neuron,and the mechanism might be that the overexpression of bcl-xl inhibit the release of cytochrome C and the activation of caspase-3.

AIM: To purify and refold the inclusion body of a human anti-HBsAg scFv with a 6?His tag, and to determine the affinity constant of the purified recombinant product.METHODS: Solubilizing in buffers containing urea or guanidine hydrochloride (GuHCl), the inclusion body was purified by IMAC, and then refolded by dialysis against urea or GuHCl, at the same time, Ni 2+ charged chelate column was utilized for in situ refolding. The affinity constant of the refolded scFv, polished by immune-affinity chromatography, was determined by non-competitive ELISA. RESULTS: The refolded scFv with highest specific bioactivity was produced by dialysis against GuHCl. Under this condition, the recovery of target protein reached (61.08?1 45)%. The affinity constant of the polished scFv was confirmed to be(2.30?0.32) ?10 7 L/mol. CONCLUSION: The inclusion body studied in this paper can be refolded efficiently under optimal dialysis condition in vitro . The antigen-binding property of this recombinant scFv is not affected by the purification tag fused to the N terminal of the protein.

PBL(Problem-Based Learning, PBL) is a problem-oriented and effective supplementary teaching method. PBL is giving a great help to improve self-learning, communication and cooperation, thinking and problems solving abilities for the students. In the process of PBL teaching, attention should be paid to two important items. One item is the role transfer for the teacher. Teacher is only a guider in PBL teaching, teacher should avoid excessive interfere of the process for keeping the passion and enthusiasm of the students. Meanwhile, students should always be realized that they are the main part in PBL teaching, they should not depend on their teacher too much. Another important item is how to find and solve the frequently encountered problems, in order to avoid students wandering from the subject, and lead them toward the main goal to get effective teaching and learning.

The aim of this Post-Marketing Surveillance study was to assess efficacy,safety and acceptance of acarbose treatment in Chinese type 2 diabetic patients under day-to-day practice conditions.A total of 2 480 patients were enrolled by 231 physicians throughout China into an open,prospective,uncontrolled,non- randomised,multi-centre study.Main efficacy parameters were the changes in fasting and postprandial blood glucose concentrations as well as in HbA-(1C) levels after acarbose treatment.The majority of patients had been previously treated with other oral anti-diabetic medication or insulin and received concomitant anti-diabetics during the mean observation period of 13.5 weeks.Most patients started on a daily acarbose dose of 50 mg t.i.d. Acarbose treatment reduced fasting blood glucose concentrations by 56.1 mg/dl ( 18 mg/dl glucose = 1 mmol/L glucose) and 2h-postprandial values by 111.3 mg/dl over the study period.HbA-(1C) decreased by 1.9% and body weight by 0.9 kg.76 acarbose-relatod adverse events occurred;two patients experienced serious adverse events. The attending physicians assessed treatment efficacy as“very good”or“good”for 90.1% of the patients, tolcrability for 89.1% and acarbose acceptance for 87.1% of the patients.Acarbose is efficacious,safe and well accepted by Chinese type 2 diabetic patients under day-to-day routine conditions,both as anti-diabetic mono- therapy and in combination with other anti-dlabetic drugs.