人参北芪片质量标准的研究

目的:建立人参北芪片的质量控制方法.方法:采用TLC法同时鉴别制剂中的人参及黄芪膏粉,采用HPLC-ELSD方法测定制剂中黄芪甲苷的含量.结果:鉴别方法专属性强,含量测定方法黄芪甲苷在1.060 8～10.608 μg之间呈良好的线性关系;人参北芪片中黄芪甲苷的平均回收率为96.4%(RSD 1.3%);结论:该方法简便、准确、分离效果好,可用于人参北芪片的质量评价.     

人参北芪片主要成分的鉴别

目的控制人参北芪片的质量，保障其临床疗效。方法采用薄层色谱（TLC）法对人参北芪片的主要成分人参、黄芪进行定性鉴别。结果TLC法准确可靠，操作简便，薄层色谱斑点清晰，阴性对照无干扰，重现性好。结论TLC法可以用于人参北芪片的质量控制。     

养正合剂质量标准研究

目的:建立养正合剂的质量控制方法。方法:用薄层色谱法对其中枸杞子、人参进行了定性鉴别;用薄层光密度法对黄芪中有效成分黄芪甲苷进行了含量测定。结果:表明本品定性鉴别色谱特征明显,易于区别;本品中黄芪甲苷含量测定线性范围为2～1 0 μg ,平均回收率95 .8% ,RSD为2 .5 %。结论:建立了该制剂的质量标准,其鉴别与含量测定方法简便、可靠、实用。     

养正合剂质量标准研究

目的建立养正合剂的质量控制方法.方法用薄层色谱法对其中枸杞子、人参进行了定性鉴别;用薄层光密度法对黄芪中有效成分黄芪甲苷进行了含量测定.结果表明本品定性鉴别色谱特征明显,易于区别;本品中黄芪甲苷含量测定线性范围为2～10μg,平均回收率95.8%,RSD为2.5%.结论建立了该制剂的质量标准,其鉴别与含量测定方法简便、可靠、实用.     

益脑康胶囊的质量控制

目的:建立益脑康胶囊的质量控制方法。方法:采用薄层色谱法定性鉴别方中主药黄芪、西洋参、三七;采用高效液相色谱-蒸发光散射法测定主药黄芪中黄芪甲苷的含量。结果:薄层定性鉴别条件适合,斑点清晰,重复性好;黄芪甲苷检测线性范围为2.15～10.75μg(r=0.9996),平均回收率为100.33%,RSD为2.62%。结论:质量控制方法简便、准确,精密度高,可以有效地控制益脑康胶囊制剂的质量。     

复方黄芪胶囊的制备及质量控制

目的:制备复方黄芪胶囊并建立其质量控制方法。方法:采用薄层色谱法定性鉴别方中主药西洋参和山茱萸;采用高效液相色谱-蒸发光散射法测定主药黄芪中黄芪甲苷的含量。结果:薄层定性条件适合,斑点清晰;黄芪甲苷检测线性范围为2.8μg～8.4μg(r=0.9999),平均回收率为99.93%,RSD=1.17%。结论:该制剂制备工艺简单,质量稳定,定量控制方法简便、准确,精密度高。     

糖尿康胶囊质量标准研究

目的建立糖尿康胶囊(黄芪、葛根、丹参、人参、黄连等)的质量标准。方法采用薄层色谱法对方中的黄连、葛根、丹参进行鉴别。用薄层扫描法对方中所含黄芪甲苷进行含量测定。结果薄层鉴别色谱特征斑点明显。黄芪甲苷在1.046~5.230μg之间呈良好的线性关系,r=0.9994,平均回收率为98.38%,RSD=1.83%(n=6)。结论本法准确、稳定性好,可作为本复方制剂的质量控制标准方法。     

参胶生血颗粒质量标准的研究

目的建立参胶生血颗粒的质量控制方法。方法采用薄层色谱法对人参、黄芪、首乌进行定性鉴别;用HPLC-ELSD法测定黄芪甲苷的含量。结果薄层色谱斑点清晰集中,易于鉴别;黄芪甲苷进样量在0.021～0.063μg范围内线性关系良好(r=0.9998),平均加样回收率为98.95%(RSD=1.27)。结论本方法灵敏、准确、重现性好、专属性强,可作为参胶生血颗粒的质量控制提供依据。     

复方黄根颗粒的质量标准研究

目的:建立复方黄根颗粒的质量标准。方法:采用薄层色谱法对叶下珠进行定性鉴别;采用高效液相色谱-蒸发光散射检测法对制剂中人参皂苷Rg1、人参皂苷Rb1、黄芪甲苷进行含量测定。结果:定性鉴别法分离度好、专属性强;人参皂苷Rg1、人参皂苷Rb1和黄芪甲苷进样量分别在1.26～12.60、0.41～4.10和2.83～28.30μg范围内,其自然对数与各自峰面积的自然对数呈良好的线性关系(r>0.999 0),三者平均加样回收率分别为99.34%、100.80%和100.10%,RSD分别为1.2%、2.4%和1.2%(n=6)。结论:所建标准可有效控制复方黄根颗粒的质量。     

健心胶囊的制备及质量控制

目的 制备健心胶囊并建立其质量控制方法.方法 将黄芪、苦参提取粉碎制成健心胶囊;采用薄层色谱法对黄芪、苦参进行定性鉴别、用薄层扫描法测定健心胶囊中黄芪甲苷的含量.结果 供试品溶液与对照品溶液薄层色谱图的斑点相同并清晰,本品每粒含黄芪甲苷不得少于0.2 mg.结论 该方法易操作,制剂质量稳定、可靠.     

Stereoselective binding of doxazosin enantiomers to plasma proteins from rats,dogs and humans in vitro

Aim： （＋）Doxazosin is a long-lasting inhibitor of a1-adrenoceptors that is widely used to treat benign prostatic hyperplasia and lower urinary tract symptoms. In this study we investigated the stereoselective binding of doxazosin enantiomers to the plasma proteins of rats, dogs and humans in vitro. Methods： Human, dog and rat plasma were prepared. Equilibrium dialysis was used to determine the plasma protein binding of each enantiomer in vitro. Chiral HPLC with fluorescence detection was used to measure the drug concentrations on each side of the dialysis membrane bag. Results： Both the enantiomers were highly bound to the plasma proteins of rats, dogs and humans [（-）doxazosin： 89.4%-94.3%; （＋）doxazosin： 90.9%-95.4%]. （＋）Doxazosin exhibited significantly higher protein binding capacities than （-）doxazosin in all the three species, and the difference in the bound concentration （Cb） between the two enantiomers was enhanced as their concentrations were increased. Although the percentage of the plasma protein binding in the dog plasma was significantly lower than that in the human plasma at 400 and 800 ng/mL, the corrected percentage of plasma protein binding was dog〉human〉rat. Conclusion： （-）Doxazosin and （＋）doxazosin show stereoselective plasma protein binding with a significant species difference among rats, dogs and humans.     

Prenatal nicotine exposure enhances the susceptibility to metabolic syndrome in adult offspring rats fed high-fat diet via alteration of HPA axis-associated neuroendocrine metabolic programming

Aim： Prenatal nicotine exposure （PNE） alters the hypothalamic-pituitary-adrenocortical （HPA） axis-associated neuroendocrine metabolic programming in intrauterine growth retardation offspring rats. In this study we aimed to clarify the susceptibility to metabolic diseases of PNE offspring rats fed a high-fat diet. Methods： Maternal Wistar rats were injected with nicotine （1.0 mg/kg, sc） twice per day from gestational day 11 until full-term delivery, and all pups were fed a high-fat diet after weaning and exposed to unpredictable chronic stress （UCS） during postnatal weeks 18-20. Blood samples were collected before and after chronic stress, and serum ACTH, corticosterone, glucose, insulin, total cholesterol, triglyceride and free fatty acids levels were measured. The hypothalamus, pituitary gland and liver were dissected for histological studies. Results： UCS significantly increased the serum ACTH, corticosterone and insulin levels as well as the insulin resistant index without changing the serum glucose, total cholesterol, triglyceride and free fatty acids levels in adult offspring rats without PNE. The body weight of PNE offspring rats presented a typical ＂catch-up＂ growth pattern. PNE not only aggravated the UCS-induced changes in the HPA axis programmed alteration （caused further increases in the serum ACTH and corticosterone levels）, but also significantly changed the glucose and lipid metabolism after UCS （caused further increases in the serum glucose level and insulin resistant index, and decrease in the serum free fatty acids）. The effects of PNE on the above indexes after UCS showed gender differences. Pathological studies revealed that PNE led to plenty of lipid droplets in multiple organs. Conclusion： PNE enhances not only the HPA axis, but also the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet after UCS in a gender-specific manner and enhances the susceptibility to metabolic diseases in adult offspring rats fed a high-fat diet.     

Hsp90 inhibitor BILBO21 enhances triptolide-induced apoptosis of human T-cell acute lymphoblastic leukemia cells in vitro mainly by disrupting p53- MDM2 balance

Aim： To investigate the effects of BILBO21, an inhibitor of heat shock protein 90 （Hsp90） alone or in combination with triptolide （TPL） on T-cell acute lymphoblastic leukemia （T-ALL） and the mechanisms of action. Methods： Human T-ALL cells line Molt-4 was examined. The cell viability was measured using M]-I- assay. Apoptotic cells were studied with Hoechst 33258 staining. Cell apoptosis and cell cycle were analyzed using flow cytometry with Annexin V/PI staining and PI staining, respectively. The levels of multiple proteins, including Akt, p65, CDK4/6, p18, Bcl-2 family proteins, MDM2, and p53, were examined with Western blotting. The level of MDM2 mRNA was determined using RT-PCR. Results： Treatment of Molt-4 cells with BILBO21 （50-800 nmol/L） inhibited the cell growth in a dose-dependent manner （the IC~ovalue was 384.6 and 301.8 nmol/L, respectively, at 48 and 72 h）. BILBO21 dose-dependently induced Go/G1 phase arrest, followed by apoptosis of Molt-4 cells. Furthermore, BILBO21 increased the expression of p18, decreased the expression of CDK4/6, and activated the caspase pathway in Molt-4 cells. Moreover, BILBO21 （50-400 nmol/L） dose-dependently decreased the phospho-MDM2 and total MDM2 protein levels, but slightly increased the phospho-p53 and total p53 protein levels, whereas TPL （5-40 nmol/L） dose- dependently enhanced p53 activation without affecting MDM2 levels. Co-treatment with BILBO21 and TPL showed synergic inhibition on Molt-4 cell growth. The co-treatment disrupted p53-MDM2 balance, thus markedly enhanced p53 activation. In addition, the co-treatment increased the expression of Bak and Bim, followed by increased activation of caspase-9. Conclusion： The combination of BILBO21 and TPL may provide a novel strategy for treating T-ALL by overcoming multiple mechanisms of apoptosis resistance.     

美国与欧洲上市后药品安全风险管理进展概述

近10年来,美国食品药品管理局（FDA）、欧洲药品管理局（EMA）及其他相关单位,对上市后药品安全性监测日益重视,在这一领域取得了显著进展,并且制定了一系列新规定。     

Molecular modeling,quantum polarized ligand docking and structure-based 3D-QSAR analysis of the imidazole series as dual AT~ and ETA receptor antagonists

Aim： Both endothelin ETA receptor antagonists and angiotensin AT1 receptor antagonists lower blood pressure in hypertensive patients. A dual AT1 and ETA receptor antagonist may be more efficacious antihypertensive drug. In this study we identified the mode and mechanism of binding of imidazole series of compounds as dual AT1 and ETA receptor antagonists. Methods： Molecular modeling approach combining quantum-polarized ligand docking （QPLD）, MM/GBSA free-energy calculation and 3D-QSAR analysis was used to evaluate 24 compounds as dual AT1 and ETA receptor antagonists and to reveal their binding modes and structural basis of the inhibitory activity. Pharmacophore-based virtual screening and docking studies were performed to identify more potent dual antagonists. Results： 3D-QSAR models of the imidazole compounds were developed from the conformer generated by QPLD, and the resulting models showed a good correlation between the predicted and experimental activity. The visualization of the 3D-QSAR model in the context of the compounds under study revealed the details of the structure-activity relationship： substitution of methoxymethyl and cyclooctanone might increase the activity against AT~ receptor, while substitution of cyclohexone and trimethylpyrrolidinone was important for the activity against ETA receptor; addition of a trimethylpyrrolidinone to compound 9 significantly reduced its activity against AT~ receptor but significantly increased its activity against ETA receptor, which was likely due to the larger size and higher intensities of the H-bond donor and acceptor regions in the active site of ETA receptor. Pharmacophore-based virtual screening followed by subsequent Glide SP, XP, QPLD and MM/GBSA calculation identified 5 potential lead compounds that might act as dual AT1 and ETA receptor antagonists. Conclusion： This study may provide some insights into the development of novel potent dual ETA and AT1 receptor antagonists. As a result, five compounds are found to be the best dual antagonists against AT1R and ETA receptors.     

树突状细胞的肿瘤个体化治疗

肿瘤免疫治疗这一概念是基于机体的免疫系统在对抗肿瘤时的调节与反应。有效的免疫治疗的最主要的优点在于相对较少的副作用,针对肿瘤细胞的靶向特异性,并且能产生对抗肿瘤特异性抗原的长期记忆[1]。     

Sodium hydrosulfide alleviates lung inflammation and cell apoptosis following resuscitated hemorrhagic shock in rats

Aim： To investigate the protective effects of hydrogen sulfide （H2S） against inflammation, oxidative stress and apoptosis in a rat model of resuscitated hemorrhagic shock. Methods： Hemorrhagic shock was induced in adult male SD rats by drawing blood from the femoral artery for 10 min. The mean arterial pressure was maintained at 35-40 mmHg for 1.5 h. After resuscitation the animals were observed for 200 min, and then killed. The lungs were harvested and bronchoalveolar lavage fluid was prepared. The levels of relevant proteins were examined using Western blotting and immunohistochemical analyses. NariS （28 pmol/kg, ip） was injected before the resuscitation. Results： Resuscitated hemorrhagic shock induced lung inflammatory responses and significantly increased the levels of inflammatory cytokines IL-6, TNF-a, and HMGB1 in bronchoalveolar lavage fluid. Furthermore, resuscitated hemorrhagic shock caused marked oxidative stress in lung tissue as shown by significant increases in the production of reactive oxygen species H202 and OH, the translocation of Nrf2, an important regulator of antioxidant expression, into nucleus, and the decrease of thioredoxin I expression. Moreover, resuscitated hemorrhagic shock markedly increased the expression of death receptor Fas and Fas-ligand and the number apoptotic cells in lung tissue, as well as the expression of pro-apoptotic proteins FADD, active-caspase 3, active-caspase 8, Bax, and decreased the expression of Bcl-2. Injection with NariS significantly attenuated these pathophysiological abnormalities induced by the resuscitated hemorrhagic shock. Conclusion： NariS administration protects rat lungs against inflammatory responses induced by resuscitated hemorrhagic shock via suppressing oxidative stress and the Fas/FasL apoptotic signaling pathway.     

生长抑素在姑息治疗中的价值

生长抑素是存在于胃黏膜、胰岛、胃肠道神经、垂体后叶和中枢神经系统中的肽激素,在中枢及外周神经系统和包括胰腺、肠道、肾上腺、肾脏和免疫细胞在内的外周组织中广泛分布,它可作用于包括脑、垂体、胰腺、肠道、肾上腺、甲状腺、肺、肾脏和免疫系统等靶器官。