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??OBJECTIVE To introduce and compare research support for rare disease and orphan drug innovation in China and United States, and provide reference for relevant policies in China.METHODS Data of main source of funding for rare disease research in two countries ie. National Institutes of Health, Food and Drug Administration in the United States and National Natural Science Foundation of China were analyzed and compared. RESULTS US NIH gives substantial support for rare disease research every year with funded capital growing. FDA Orphan Products Grants program provides incentives for sponsors to develop products for rare diseases. In China, however, there is no specific support project for rare disease research, and there is a huge gap in funding efforts for rare disease research between China and the United States. CONCLUSION China should establish rare disease research center to promote rare disease research and set up specific funding for rare diseases research, increase efforts to support research and innovation for rare diseases and orphan drugs, in order to protect the health interests of patients with rare diseases.     

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??OBJECTIVE To provide references for effective quality control of soft capsules and discuss the applicability of method for dissolution test of soft capsules. METHODS Based on analyzing dissolution requirements of soft capsules, we were compared the differences of METHODS for dissolution test in the pharmacopoeias of several countries with current correlative research from home and abord. RESULTS The dissolution characteristics of soft capsules are more complex than common oral solid dosage forms, and the requirments are different in the pharmacopoeias of several countries. The formula of contents, hydrophilicity, rupture test and crossliking have impacts on the dissolution characteristics as well as dissolution device and so on. CONCLUSION In order to develop the method for dissolution test of soft capsules, the dissolution device and medium, rupture test and in vitro-in vivo correlation etc. should be studied.     

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??OBJECTIVE To compare different pretreatment methods for determination of 10 metallic elements including Pb, Cd, As etc in Ganoderma extract. METHODS Microwave digestion, automatic wet digestion and electrical heating wet digestion methods were used to conduct pretreatment of Ganoderma extact, then the contents of Pb, Cd, Hg, As, Cu, Fe, Mn, Zn, Al, Zn and Cr were determined by inductively coupled plasma mass spectrometry(ICP-MS). RESULTS The contents of metallic elements determined by the three kinds of digestion methods were not statistically different except for Hg(P??0.05). The average recoveries of Hg in the Ganoderma samples were 65.28% and 70.39% when processed by automatic digestion and electrical heating digestion method, respectively, much lower than the value of microwave digestion method(98.31%). The recoveries of other metallic elements ranged from 92.19% to 103.26% by the three kinds digestion methods, with RSDs less than 5%. CONCLUSION Automatic digestion and electrical heating digestion methods are unable to meet the requirement for simultaneous determination of the 10 kinds of metallic elements in Ganoderma extract, however, microwave digestion method can. As the microwave digestion method is simple and rapid, so it is more suitable for the determination of heavy metals in Ganoderma. It is suggested to choose appropriate sample digestion method according to specific determination requirement on metallic elements in actual situation.     

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??To provide scientific and theoretical basis for the further study and reference for the development and efficient use of the medicinal plants, the extraction and separation technology of Celtis sinensis and its main chemical components and pharmacological effects were summarized. Literatures were reviewed, and the key information was classified and summarized. A large number of flavonoids, triterpenoids, phenols, anthraquinones and amides have been isolated from the plants. Extract of Celtis shows diversed pharmacological activities, such as antioxidant, anti-inflammatory, antibacterial, anti-tumor and so on. Further studies should be carried out on Celtis sinensis, which is abundant in our country and has high medicinal value and broad application prospect, for its better development and utilization.     

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??OBJECTIVE To develop a method for simultaneous determination of six iridoid glycosides from Cymbaria dahurica.METHODS Cymbaria dahurica collected from different regions were determined by HPLC. The separation was performed on Inertsil ODS-SP column (4.6 mm??250 mm,5 ??m) at 30 ?? by gradient elution with CH₃OH-H₂O as the mobile phase, with the detection wavelength set at 210 nm.RESULTS Under the chromatographic conditions adopted in this study, all the calibration curves exhibited good linearity (r>0.999 4) in a relatively wide concentration range. The recovery of the method was within the range of 95.0%-98.0%, and the RSD was less than 3%. The contents of all the compounds (S1-S6) in samples from different habitats varied significantly.CONCLUSION The quantitative method for evaluating the quality of Cymbaria dahurica is established and can be used for the quality control of Cymbaria dahurica.     

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??OBJECTIVE To optimize the formulation of ambroxol hydrochloride sandwich osmotic pump tablets using Box-Behnken design response surface method. METHODS Firstly, significant factors, including amount of glucose, ratio of pore former to weight of coating, and thicknesss of coating, were chosen carefully by single-factor METHODS, then Box-Behnken design-response surface method was adopted to understand the effects of these factors on the drug release by using similarity factor f₂ as evaluation index. And multiple linear regression model and quadratic polynomial equation were established to evaluate the relationship between these factors and similarity factor f₂. Secondly, the permeation mechanism of sandwich osmotic pump was studied carefully by SEM and drug release behavior investigation. RESULTS The quadratic polynomial equation was ideal to fit the prediction result of drug release; the optimal formulation according to Design-Expert8.0.5 software was established as follows: 50 mg of glucose, 8% of pore former, 9% of coating weight. The f₂ was approximate 89.33 compared with ideal drug release curve, which was relatively close to the model-predicted f₂ value (88.89). Through investigation of permeation mechanism, it was found that the drug release from this delivery system was driven by osmotic pressure difference between the interior of tablets and the release medium. By means of SEM observation, it was shown that some pores on the coating surface were produced after drug release in the medium, but few before drug release, which cued that a lot of medium got into the interior of tablets through the tunnels formed by the porogen in the coating. CONCLUSION Box-Behnken design method can be used to optimize the formulation of sandwich osmotic pump tablets.     

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??OBJECTIVE To identify a Yunnan herbal medicine-Corydalis Taliensis Herb. METHODS Pharmacognostic METHODS have been used on the original plant,macroscopic characteristics ,microscopic tissue structure and powder characteristics of Corydalis Taliensis Herb. RESULTS Corydalis Taliensis Herb is the dried herb of Corydalis taliensis.Its stems five prism,leaves 2- to 3-ternate divided, flowers, spurred,purple, violet or pink, starchy and bitter. The size of epidermal cells are not the same, and some of cell outer wall papillate;stone cells visiblly,fibres with various shapes. CONCLUSION Experimental RESULTS can be used for authenticity identification and quality control of Corydalis Taliensis Herb.     

哮喘片微生物限度检查法的建立及方法学验证

目的:建立哮喘片微生物限度检查的方法并验证.方法:按2010年版《中国药典》,用大肠埃希菌、枯草芽胞杆菌、金黄色葡萄球菌、黑曲霉和白色念珠菌对哮喘片进行微生物限度检查方法学验证试验.结果:哮喘片对细菌中的金黄色葡萄球菌、枯草芽孢杆菌有较强的抑制作用.结论:本品对细菌的计数方法为培养基稀释法;霉菌、酵母菌计数方法为平皿法;控制菌检查可采用常规法检验.该方法用于哮喘片的质量控制有效、可行.     

胎盘口服液微生物限度检查方法的建立及验证

目的：建立胎盘口服液微生物限度检查方法。方法：按《中国药典））2010年版一部微生物限度检查方法的要求进行验证试验。结果：胎盘口服液微生物限度检查细菌数、霉菌和酵母菌数测定方法取原液采用常规法（1mL／皿）进行验证试验,试验组的菌回收率（％）均不低于70％;控制菌（大肠埃希菌、沙门菌）检查方法用大肠埃希菌取10-1供试液采用常规法（100mL／瓶）,沙门菌取原液采用常规法（200mL／瓶）进行验证试验,试验组、阳性对照组检出大肠埃希菌、沙门菌,阴性对照组无菌生长。结论：胎盘口服液微生物限度检查细菌数、霉菌和酵母菌数测定方法可用常规法（1mL／皿）测定,控制菌（大肠埃希菌、沙门菌）检查方法可用常规法（100mI。／瓶、200mL／瓶）进行检查。     

基于有限采样法的骨肉瘤患者甲氨蝶呤体内暴露量估算模型的建立与验证

目的 采用有限采样法估算骨肉瘤患者静脉滴注大剂量甲氨蝶呤(high dose methotrexate, HD-MTX)后的体内药物暴露量,即药时曲线下面积(area under the drug concentration versus time curve, AUC_0-t)。方法 34名骨肉瘤患者共进行67个周期HD-MTX化疗,分别于滴注结束时、开始滴注10,24,48和72 h收集患者血液样本,采用化学发光免疫法(CMIA)进行MTX血药浓度测定。计算得到患者MTX临床药动学参数后,经多元线性回归,建立基于有限采样法的AUC_0-t估算模型。采用Bootstrap法和Jackknife法进行模型准确性验证,采用Bland-Altman分析法评估有限采样法与经典药动学方法之间的一致性。通过绘制ROC曲线,评估AUC_0-t对HD-MTX不良反应的预测性能。结果 综合考虑临床可操作性及准确性,选择两点(c_max、c_{24 h})模型用于MTX AUC_0-t的估算,回归方程为AUC_0-t=6.36c_max+161.30c_{24 h},r²为0.933,平均预测误差为0.47%,均方根误差为6.78%。AUC_0-t对肝功能损伤、骨髓抑制及消化道反应等药物不良反应具有良好的预测能力,P<0.05。结论 基于c_max、c_{24 h}两点估算的有限采样法可以用于骨肉瘤患者HD-MTX药物暴露量的估算,方法简便,易于临床开展,可为MTX个体化用药提供参考。     

Caco-2细胞单层模型的建立与验证

 目的研究建立Caco-2细胞模型的方法,并确认Caco-2细胞模型的正常生长特性,以在日常培养中进行监控。方法常规培养条件下,Caco-2细胞以每1 mL含8×10⁴个的接种密度接种于Millicell插入式培养皿中,培养21 d后用光镜、电镜、细胞密度测定等方法检查细胞的形态学及生长特点,测定碱性磷酸酶活性、跨膜电阻、荧光素钠透过量以检验细胞单层的极化现象和致密程度。结果Caco-2细胞单层在生长10 d以后均匀、致密,21 d后微绒毛、碱性磷酸酶、紧密连接等呈不对称分布,跨膜电阻达到600Ω·cm²,荧光素钠透过量为4.16μg·h^-1·cm^-2,而同样条件下空白膜的透过量大于240μg·h^-1·cm^-2。结论本培养条件下,Caco-2细胞单层形态与小肠上皮细胞类似,跨膜电阻、标志物透过量均达到要求,可以作为研究小肠药物转运过程的体外模型。     

吸附破伤风疫苗血清学效价检测方法的建立及初步验证

目的 建立吸附破伤风疫苗血清学效价检测方法并对其进行初步验证.方法 通过对采血时间、有效剂量范围的选择,建立附破伤风疫苗血清学效价检测方法,在3个实验室对10批破伤风疫苗用小鼠攻毒法和本研究方法进行19次效价检测,对2种方法的检测结果进行初步验证.结果 建立了吸附破伤风疫苗血清学效价检测方法.吸附破伤风疫苗小鼠攻毒法和...     

占星预言2006-2010掀起淘金狂潮

投资黄金，一年获利70％！ 只需要有1000多元的闲散资金，在一年间即可获得70%的投资回报，这或许就是在黄金投资市场即将上演的神话，也是国人继股市，债市，期市，邮市和房产市场之后，又一个重要的投资渠道。     

Genotoxic and antigenotoxic properties of Baccharis trimera in mice

Ethnopharmacological relevance

Baccharis trimera (Less.) (Asteraceae) is a native plant from Brazil. Also known as “carqueja”, it is popularly used to treat liver diseases, diabetes, as well as digestive disorders, mainly by women with lower socioeconomic status.

Aim of the study

The aim of the present study was to investigate the in vivo genotoxic/antigenotoxic and mutagenic potential of this plant, using the comet and the micronucleus assays.

Material and methods

Female adult mice were treated with 500, 1000 or 2000 mg/kg of B. trimera aqueous extract (Bt-AE) by gavage for three consecutive days.

Results

Independently of the dose, no genotoxic effect was observed in blood and liver samples analyzed by the comet assay. Conversely, B. trimera showed an antigenotoxic effect in blood from treated mice, thus protecting cells against oxidative DNA damage induced by the ex vivo treatment with hydrogen peroxide. In addition, Bt-AE showed in vitro antioxidant activity, assessed by DPPH and xanthine oxidase assays, suggesting that the observed antigenotoxic effects might be related to its antioxidant properties.

Conclusions

However, the extract increased the frequency of micronucleus in bone marrow of treated mice, indicating a chromosomal mutagenic activity. Thus, medicines prepared from this plant should be used with caution, although the results also suggest antigenotoxic effects for B. trimera aqueous extract.     

穴位贴敷疗法对失眠障碍患者PSQI改善率临床预测模型的建立与验证*

目的：构建穴位贴敷对失眠障碍（ID）患者PSQI改善率结局影响因素的临床预测模型,为穴位贴敷疗法改善ID患者的失眠结局提供预测的思路及方法。方法：采用回顾性队列研究方法,收集2019年6月~2020年6月于中国中医科学院针灸医院、丰体时代社区卫生服务站两个中心接受穴位贴敷疗法治疗的64例ID患者0周、1周、2周、3周、4周、6周的临床资料（2例剔除,共372例数据）。采用单因素Logistic回归分析、向前向后逐步回归分析用于筛选构建列线图预测模型的变量,根据最小赤池信息准则（AIC）选定最优模型,进一步根据筛选出最优模型因素的回归系数利用 R语言中的“rms”包构建列线图预测模型,并通过受试者工作特征曲线（ROC）下面积（AUC）评估模型的区分度,校准曲线和Hosmer-Lemeshow拟合优度检验评估校准度,利用“Bootstrap重复抽样法”对模型进行内部验证。结果：①治疗时间、病程≤12月、12月＜病程≤36月、疲劳程度、既往是否使用促眠药物、一般健康状况、社会功能、躯体疼痛、肝郁化火组合AIC为300.31,为最优模型,方差膨胀因子（VIF）均＜5,容忍度均＞0.5,提示多重共线性的可能性较小,是穴位贴敷疗法对ID患者失眠结局的独立预测因素;②预测模型的ROC曲线下面积AUC为[0.856,95%CI（0.814,0.898）],说明该预测模型具有较好的区分度;各变量因素单独预测结局事件的ROC曲线下面积AUC位于0.5至0.8之间,均低于联合预测结局事件的AUC值,表明联合预测较各变量因素单独预测具有更好的区分度及预测能力;③校准曲线显示预测模型的拟合曲线与理想曲线较为接近,表明该模型具有较好的校准度;④Brier 得分为 [0.125,95%CI（0.105,0.145）],说明该预测模型总体预测性能较好;Hosmer-Lemeshow 拟合优度检验显示 P=0.152（P＞0.05）, 提示该模型拟合良好。结论：以治疗时间、病程≤12月、12月＜病程≤36月、疲劳程度、既往是否使用促眠药物、一般健康状况、 社会功能、躯体疼痛、肝郁化火构建的临床预测模型具有较好的预测效能,可为穴位贴敷疗法治疗失眠障碍的临床决策提供一定的参考价值。     

Arrowsmith在预测中药副作用研究中的思路探讨

美国芝加哥大学情报学教授Don．R．Swanson创立的情报学知识发现方法是揭示非相关文献及学科间隐秘联系的强有力的工具。本文简要介绍了闭合式的知识发现方法及其实现工具Arrowsmith软件系统,并对其在预测中药不良反应研究中的思路进行探讨。     

Genotoxic and Antigenotoxic Activity of Acerola (Malpighia glabra L.) Extract in Relation to the Geographic Origin

Malpighia glabra L, popularly known as acerola, is considered a functional fruit and therefore is taken to prevent disease or as adjuvant to treatment strategies, since the fruit is an undeniable source of vitamin C, carotenoids, and flavonoids. Acerola is a natural source of vitamin C, flavonoids, and carotenoids. Its chemical composition is affected by genetic uniformity of the orchards and environmental factors. Considering the extensive growth of the culture of acerola in Brazil as well as its widespread use, this study evaluates the genotoxic and antigenotoxic activity of acerola in relation to geographical origin using the comet assay in mice blood cells in vitro. No acerola samples showed potential to induce DNA damage, independently of origin. Also, for antigenotoxicity activity, only the acerola sample from São Paulo reduced DNA damage induced by hydrogen peroxide (by about 56%). The sample from Ceará showed good antioxidant activity by the 2,2‐diphenyl‐1‐picrylhydrazyl assay, in agreement with its higher rutin, quercetin, and vitamin C levels. Additional studies with other treatment regimens are necessary to better understand the impact of the complex mixture of acerola on genomic stability. Copyright © 2012 John Wiley & Sons, Ltd.