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??OBJECTIVE To study the chemical constituents of Fomes fomentarius (L.Ex.Fr.). METHODS The compounds were isolated by chromatography on silica gel column, Sephadex LH-20 column, and their structures were elucidated by spectral analysis. RESULTS Six compounds were obtained and identified as fomentarinin (1), 2-hydroxy hexacosanoic acid ethyl ester (2),syringic acid (3), syringyl alcohol (4), vanillin (5), and ergosta-7,22-diene-3,6-dione (6), respectively. CONCLUSION Compound 1 is a new compound, and compound 2-6 are isolated from the fungus for the first time.
     

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??OBJECTIVE To systematically evaluate the economics of saxagliptin for treatment of type 2 diabetes mellitus. METHODS PubMed, Embase, Cochrane Library, NHS EED, CNKI, Wanfang and CBM were systematically searched. Literatures were screened according to pre-defined inclusion criteria. The quality of included studies were evaluated by CHEERS statement and the economic RESULTS were systematically analyzed. RESULTS Eight cost-effectiveness analyses were included, one of which was conducted in China. Patients among the studies all had blood glucose non-adeguately controlled by monotherapy. When added on to metformin, saxagliptin was cost-effective compared with sulfonylureas (glipizide and glimepiride) and thiazolidinediones (pioglitazone and rosiglitazone). When added on to metformin or sulfonylureas, saxagliptin was cost-effective compared with NPH insulin. CONCLUSION Saxagliptin represents a cost-effective option in treatment of type 2 diabetes mellitus patients with non-adequately controlled blood glucose after monotherapy.     

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??OBJECTIVE To analyze the connotation and composition of the clinical value of drugs, and to build the index system for the evaluation of drug's clinical value, hence to provide references for its scientific evaluation. METHODS We designed the preliminary constructs index system referencingmedicine clinical evaluation indicatorsof German and French firstly. And then the expert interview and Delphi survey were used to analysis to determine the index system and index weight of medicine clinical evaluation. RESULTS The classified index system of the clinical value was established, which was composed of 2 first-grade indexes including clinical value and innovation value and 15 grade two indexes. Experts were invited to assess the value ranking according to the background information of rosuvastatin, atorvastatin and simvastatin statin drugs by their generic names. The expert's scoring results were summarized to determine the sequence. And it were compared with the average market prices in Germany, France, Britain, the United States, South Korea, Japan and analyzed. CONCLUSION The clinical value of drugs is an international standard for determining the reasonable price of drugs. This research method is feasible to determine the drug prices sequencing by the classified clinical value of drugs in the same kind of product. The price sequencing of some generic names of statin drugs did not correspond with its clinical value sequence, and the price can not reflect its value. The integrity and authenticity of the background data directly determine the classification of the clinical value. Various parties are needed to participate in providing detailed data and information.     

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??Polygonati Rhizoma as one of the most common Chinese herbal medicine and food was widely distributed in China. In TCM clinic, it was used for diabetes, hyperlipemia and rehabilitation therapy of cancer. Nowadays, with the rapid development of health industry, Polygonati Rhizoma shows excellent functions on healthcare, and then a surge of demands was coming. But there are so many species belongs to this genus and the classification criteria are not unified, so some important problems become urgently to be resolved, such as how to guarantee the quality and how to keep sustainable development. In this paper, the origin, distribution in China, chemical composition, pharmacological, and clinical application are reviewed. Its prospect is discussed to be helpful to promote the comprehensive development of Polygonatum.     

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??OBJECTIVE Blood tends to deposit in atrium to form thrombus in patients with atrial fibrillation. Patients with diabetes are in high coagulation state, for whom thrombosis is easy to occur. The number of diabetic patients with atrial fibrillation is large. Warfarin is one of the most widely used oral anticoagulants, which can cause major or fatal bleeding, so it is necessary to perform regular monitoring of international normalized ratio (INR) on all patients treated with warfarin. New kinds of antidiabetic drugs are widely used in clinic, among which a lot affect INR levels achieved with warfarin therapy. Clinical pharmacists should pay attention to drug interactions and monitor adverse drug reactions. As a new antidiabetic drug, exenatide has less reports of interaction with warfarin. The characteristic of the interaction between exenatide and warfarin was investigated, with the aim to optimize the rational and individualized medication. METHODS A case was introduced in which exenatide was administrated combined with warfarin, so that the possible mechanism of exenatide affecting to warfarin were analyzed. RESULTS INR declined from 2.13 to 1.57 after exenatide being added, and decreased further to 1.43 with concurrency of the increasing exenatide dose. On the contrary, INR was on rise as result of discontinuing exenatide. At last, INR returned to 1.78 when the patient discharged. CONCLUSION Exenatide inhibited the absorption of warfarin, which lead to INR decline attributed to its effect of slowing down the gastric emptying. When exenatide and warfarin are combined,the dose of warfarin must be adjusted based on INR under clinical monitoring.     

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??OBJECTIVE To study and collate the literature on rare diseases in domestic and abroad, and comparative analysis, provide a scientific basis for the domestic rare diseases research. METHODS Retrieved the Web of Science, China National Knowledge Infrastructure from January 2011 to June 2016 published literature about rare diseases. RESULTS Through the screening of literature, finally determine the 200 articles for analysis. It is divided into seven research directions:rare diseases policy research, rare diseases legal and regulatory research, rare diseases medical social security study, orphan drugs availability research, orphan drugs economic evaluation study, orphan drug development research, rare diseases defined standard research. CONCLUSION Rare diseases policy research is the focus of research both domestic and abroad. Compared with foreign countries, the domestic research on the availability and economic evaluation of orphan drug is less, especially the economic evaluation research is almost blank. It is suggested that the researchers study the multiple aspects of rare diseases and drugs, and to provide the basis and reference for build rare disease policy in China.In addition to the field of rare diseases research, rare diseases drugs face many difficulties in pharmaceutical research, production and supply.The precondition to solve these problems is the nation formulate specific policies and regulations for rare diseases,and then clear the official definition standards of rare diseases,establish relevant policies to encourage pharmaceutical companies to develop rare diseases drugs.     

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??OBJECTIVE To synthesize 5-substituted indole-3-deoxypodophyllotoxin derivatives and study their antitumor activity. METHODS The target compounds were synthesized through a series of reactions and their anti-tumor activity in vitro were evaluated against Hela, K562 and K562/A02 cell lines by MTT as assay. RESULTS Ten target compounds were synthesized and confirmed by ¹H-NMR, ¹³C-NMR, and HR-ESI-MS. All the target compounds had different degrees of cytotoxic activity in vitro. Most of the compounds had significant anti-MDR activity in vitro. CONCLUSION 5-Substituted indole-3-deoxypodophyllotoxin derivatives have good antitumor activity and worth of further study.     

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??OBJECTIVE To determine the effects of saxagliptin and exenatide on humerus cancellous bone of diabetes-induced osteopenia rats by histomorphometry. METHODS Thirty-five Cases of female SD rats were randomly divided into normal group (N group, n=7), control group (C group, n=7), and the remaining rats were used to establish the type 2 diabetic model by combination of high-fat&sugar-diet feeding for 4 weeks and then low-dose streptozotocin injection(STZ, 30 mg??kg^-1) . After 10 d, the oral glucose tolerance test and the fasting blood glucose were measured, rats with high OGTT(2 h) above 11.1 mmol??L^-1 and high FBG above 16.7 mmol??L^-1 were divided into model group (M group, n=5), saxagliptin group (G group, n=5) and exenatide group (D group, n=6), and continuously treated for 30 d. The left humerus (proximal humeru metaphometry, PHM) were fixed with 4% paraformaldehyde for 48 h, uncalcified embedded in methyl methacrylate after dehydrated and cleared, and sections were taken for bone histomorphometry after Masson-Goldner Trichrome stained. RESULTS In PHM, there was no statistical significance between N and C group, the trabecular bone area ratio( BV/TV) and trabecular quantity were significantly decreased (P??0.01) in M group, while the trabecular separation degree was increased, comparing with those in C group (P??0.01), and the trabecular bone area ratio( BV/TV) and trabecular quantity in G and D group were higher (P??0.01) than those of model rats, while the trabecular separation degree was decreased, comparing with those in M group (P??0.01). Cell parameters showed no statistical significance between N and C group, the osteocllast number and percentage of osteocllast surface perimeter were significantly reduced(P??0.05, P??0.01) in M group, while the osteoclast number and percent osteocllast surface perimeter were significantly increased (P??0.01) as compared with those in C group, saxagliptin and exenatide were found to significantly induce osteocllast number (P??0.01) and percentage of osteoblast surface perimeter (G group P??0.05, D group P??0.01), while reduce osteoclast number (P??0.01) and percent osteoblast surface perimeter (P??0.05) compared with M group. In growth-plate, there was no statistical significance between N and C group, the thickness of growth-plate and the diameter of the mast cells were reduced in M groups (P??0.01), while the thickness of growth-plate (P??0.01) and the diameter of the mast cells (P??0.05) were increased in G and D group,compared with M group. CONCLUSION Therapeutic effects of saxagliptin and exenatide on diabetes -induced osteopenia rats was showed, and the mechanism may be related to the improved growth rate of growth-plate and the changed bone turnover status.     

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??OBJECTIVE To evaluate the anti-hepatitis B virus (HBV) activity of herpetrione nanosuspension (PEDX-NS) both in vitro and in vivo. METHODS HepG2 2.2.15 cells and duck hepatitis B virus (DHBV) infected ducks as in vitro and in vivo models were used to compare the anti-HBV activity of PEDX-NS and PEDX coarse suspension (PEDX-CS). RESULTS In the HepG2 2.2.15 cell, PEDX-NS effectively suppressed the secretion of the HBV antigens (HBsAg and HBeAg) in a dose-dependent manner with significant difference from PEDX-CS (P<0.05 or P<0.01). In the in vivo evaluation, PEDX-NS with high dose (100 mg??kg^-1) and middle dose (60 mg??kg^-1) significantly reduced the serum HBV DNA level (P<0.05 or P<0.01) and the effect was better than that of PEDX-CS (P<0.05 or P<0.01). CONCLUSION The result revealed that PEDX-NS exhibits anti-HBV activity both in vitro and in vivo and its effect was superior to that of PEDX-CS. The mechanism is probably that the small particle size of PEDX-NS provides a large specific surface area that resulted in better absorption in vivo, thus enhancing its anti-HBV activity.
     

白藜芦醇及其衍生物抗乙型肝炎病毒体外实验研究

 目的 探讨白藜芦醇(resveratrol,反式3,4′,5-三羟基-二苯乙烯)及其衍生物体外抗乙型肝炎病毒(HBV)的作用,及相关 的量效关系与构效关系。方法 将白藜芦醇及其衍生物作用于HepG2.2.15细胞系,MTT法检测样品对HepG2.2.15细胞的毒 性,ELISA法检测细胞上清中HBsAg,HBeAg的变化,实时荧光定量PCR法检测细胞与其上清中总HBV DNA含量,流式细胞仪 检测白藜芦醇时HepG2.2.15的凋亡作用,进行综合评价。结果 白藜芦醇对抑制HepG2.2.15细胞分泌HBsAg,HBeAg治疗指 数(TI)分别为(3.26±0.39),(2.91±0.12);在低毒或无毒浓度(0.11 mol·L^-1)下降低DNA拷贝数;呈浓度依赖性诱导 HepG2.2.15细胞凋亡。结论 白藜芦醇及其衍生物在体外有一定的抗乙型肝炎病毒作用,可能是通过抑制HBV DNA复制, 诱导感染HBV的HepG2.2.15细胞凋亡而发挥抗病毒活性。综合评价白藜芦醇及其衍生物的活性,即白藜芦醇苷(Rn1)、甲氧 基取代羟基的苷[4′-甲氧基-3,3′,5-二苯乙烯-3-葡萄糖苷(Rn3)]效果较好。     

氧化苦参碱体外抗乙型肝炎病毒作用

目的:体外观察氧化苦参碱(OM)抗乙型肝炎病毒(HBV)作用,并初步探讨其作用机制.方法:用125,250,500,1000,2000 mg·L-1OM连续作用于90％汇合度的HepG2.2.15细胞9d,以MTT比色法观察药物细胞毒性;用酶联免疫法测定细胞上清液中乙型肝炎病毒e抗原(HBeAg),乙型肝炎病毒s抗原(HBsAg);采用荧光定量PCR法(FQ-PCR)测定细胞上清液中HBV DNA,细胞中HBV DNA和共价闭合环状DNA(cccDNA).结果:OM对细胞内HBV DNA和cccDNA,以及细胞外HBV DNA均有抑制作用,随着浓度升高抑制作用加强,2000 mg·L-1OM对细胞内HBV DNA,cccDNA和细胞外HBV DNA的抑制率分别为64.56％,52.12％,54.25％;对HBsAg和HBeAg的分泌也有抑制作用,且浓度越高、处理时间越长,抑制作用越明显;在相同条件下对HBsAg的抑制作用强于HBeAg,OM浓度为2000 mg·L-1时对HBsAg和HBeAg的抑制率分别为51.59％,17.88％.结论:OM能有效抑制HepG2.2.15细胞中HBV复制,该作用是抑制病毒核酸复制和基因表达的结果.     

Inhibiting effects of the ethanol-soluble extracts from the dried rhizoma of Garcinia oblougififolia on hepatitis B virus in vitro]

Comparing with Ara-Amp, the effects of the ethano-soluble extracts from the dried rhizoma of Garcinia oblougififolia Champ (GOC) on HBeAg and HBsAg expression in 2.2.15 cells, which came from transfected HepG2 cells with coloned HBV DNA, were studied. The results showed that the extracts of GOC had a marked inhibition effects on HBeAg adn HBsAg which expressed by 2.2.15 cells, the effective concentration was range from 195 to 780 micrograms/ml.     

六月青含药血清对HepG2.2.15细胞系HBsAg与HBeAg表达的影响

目的 观察六月青(Liuyueqing,LYQ)含药血清的体外抗乙型肝炎病毒的作用.方法 以MTT法检测药物在体外对HepG2.2.15细胞的生长抑制作用,采用酶联免疫法(ELISA法)检测HepG2.2.15细胞上清液中HBsAg、HBeAg的滴度.结果 LYQ含药血清对HepG2.2.15细胞50%生长抑制率的给药剂量为11.56 g·(kg·d)-1;而对HepG2.2.15细胞分泌HBsAg 50%生长抑制率的给药剂量为0.178 g·(kg·d)-1,其治疗指数(TI)为64.94;另外,LYQ含药血清对HBeAg抑制作用不明显.结论 LYQ含药血清在体外有显著的抗HBV的作用,且毒性较低.     

甘草甜素对HepG2．2．15细胞株HBV感染的影响

目的探讨甘草甜素（GL）对HepG2．2．15细胞上清液中HBsAg、HBeAg、HBVDNA的作用,及对细胞存活率的影响。方法实时荧光定量PCR检测HBVDNA的表达,ELASA检测HBV所分泌抗原,MTT检测细胞的增殖活性,计算细胞存活率。结果给药后各组HBsAg分泌结果显示总体均数间差异显著（P=0．000）,GL各组与对照组比较差异有统计学意义（P〈0．01）,抑制作用存在剂量依赖关系;而对HBeAg水平的影响因剂量不同而表现为升高和降低两种趋势,除50pg／mL组外,其余各组与对照组比较,差异均有统计学意义（P〈0．05）,但800μg／mL组HBeAg分泌增加,400μg／mL以下组为HBeAg降低;HBVDNA的表达显示GL各组与对照组比较,差异均有统计学意义（P〈0．05）,但400pg／mL以下组为HBVDNA降低,800μg／mL组出现HBVDNA复制增强;MTT实验显示,200μg／mL以下3个剂量组均可促进细胞增殖（P〈0．01）,400、800μg／mL2组均显著抑制细胞增殖（P〈0．01）;MTT分别与HBeAg和HBVDNA水平呈显著负相关（P〈0．01）,但与HBsAg呈显著正相关（r=0．869,P=0．000）。结论GL对HepG2．2．15细胞株上清中的HBeAg和HBVDNA水平可能具有双向作用,而对HBsAg具有剂量依赖的抑制作用,提示GL的使用应注意选择适应证及合适的剂量。     

槐果碱体外对HepG2.2.15细胞分泌HBsAg HBeAg的影响

目的:探讨槐果碱的体外抗乙型肝炎病毒作用。方法:采用HepG2.2.15细胞模型进行体外培养,给予不同浓度槐果碱,以拉米夫定作阳性对照,作用9天后检测上清液中HBsAg、HBeAg的分泌,观察药物对HepG2.2.15细胞分泌HBV病毒抗原的影响,同时以MTT法检测药物在体外对HepG2.2.15细胞的生长抑制作用,从而评价药物的抗HBV作用。结果:药物作用9天后,槐果碱对HepG2.2.15细胞的50%生长抑制率(TC50)为0.002M,对HepG2.2.15细胞分泌HBsAg的50%抑制率(IC50)为4.9uM,其治疗指数(TI=TC50/IC50)为408.16;而拉米夫定对HepG2.2.15细胞分泌HBsAg的抑制率在所选浓度范围内均低于50%。槐果碱对HepG2.2.15细胞分泌HBeAg的抑制率在所选浓度范围内均低于50%,但明显优于拉米夫定对HepG2.2.15细胞分泌HBeAg的抑制率。结论:槐果碱在体外具有显著的抑制HepG2.2.15细胞分泌HBsAg、HBeAg的作用,是一个高效低毒的抗乙肝病毒的有效药物。     

青钱柳提取物对HepG2 2.2.15细胞HBsAg和HBeAg表达的影响

目的研究青钱柳提取物体外抗乙肝病毒作用。方法青钱柳用75%乙醇提取后按溶剂极性萃取,获得的三氯甲烷部位经柱层析得到Fr.2组分。体外培养HepG2 2.2.15细胞,MTT法检测青钱柳提取物Fr.2组分对HepG22.2.15细胞的细胞毒作用,用ELISA法检测HepG2 2.2.15细胞培养液中HBsAg和HBeAg的表达。结果青钱柳提取物Fr.2组分对HepG2 2.2.15细胞无明显的细胞毒作用。与对照组比较,Fr.2组分对HBsAg和HBeAg的表达均有显著性抑制作用(P<0.01或0.05)。结论青钱柳提取物体外具有较强的抗乙肝病毒作用。     

中国圆田螺多糖体外抗乙肝病毒的实验研究

目的:探讨中国圆田螺多糖(PCC)体外抗乙肝病毒的生物学活性.方法:以HepG2 2.2.15细胞系为体外实验模型.MTT法检测细胞毒性,将不同安全浓度的PCC及阳性对照药物3TC作用于此细胞系,实验同时设不加药物的细胞对照,第9天收集细胞培养上清液.采用ELISA法测定各组细胞培养上清液中HBsAg,HBeAg水平,荧光探针定量PCR检测HBV-DNA含量.结果:PCC在HepG2 2.2.15细胞培养中的TCo为1g·L-1,TC50 ＞10 g·L-1,对细胞毒性较小.PCC对HepG2 2.2.15细胞HBsAg,HBeAg分泌的IC50分别为0.501,0.401 g·L-1,SI分别为＞19.96和＞24.94.PCC可以有效抑制HBsAg,HBeAg的分泌,且PCC对HBeAg的抑制效果优于HBsAg.PCC在0.1,1g·L-1(P＜0.05)对HepG2 2.2.15细胞中的HBV-DNA有明显的抑制作用.结论:中国圆田螺多糖具有一定的体外抗HBV活性,且毒性较小,具有良好的应用前景.     

聚乙二醇化干扰素α-2a治疗HBeAg阳性慢性乙型肝炎40例临床疗效观察

目的考察聚乙二醇干扰素α-2a（派罗欣）对HBeAg阳性慢性乙型肝炎患者的疗效。方法符合要求的慢性乙型肝炎患者40例,所有患者均使用派罗欣180ug皮下注射,1次/周,连续48周,治疗期间不使用其它抗病毒药物。选取肝功能、乙型肝炎病毒标志物、HBVDNA作为检测指标。结果治疗48周后,ALT/AST复常率72.5%（29/40）,HBsAg血清转换率12.5%（5/40）,HBeAg血清转换率45%（18/40）,HBVDNA转阴率65%（26/40）。结论派罗欣治疗慢性乙型肝炎能获得HBsAg血清转换,且安全性好。