基于网络药理学探讨清热活血方抗类风湿性关节炎的作用机制

目的:清热活血在治疗类风湿性关节炎(RA)中效果显著,但其成分多样,作用机制不明,通过网络药理学方法探讨清热活血方抗RA的作用机制。方法:利用中药系统药理学数据库与分析平台(TCMSP)筛选药物成分并利用SwissTargetPrediction数据库预测药物靶点,同时通过药物数据库(Drugbank)和在线人类孟德尔遗传数据库(OMIM)收集疾病靶点。将药物靶点与疾病靶点取交集,拓展并拓扑获取关键靶点,利用DAVID数据库对关键靶点进行基因本体论(GO)分类富集分析和京都基因和基因组百科全书(KEGG)通路富集分析,通过Centiscape计算获取hub节点。结果:从清热活血方中筛选出活性成分31个,预测靶点419个,数据库挖掘疾病靶点共430个。将药物靶点与疾病靶点取交集、拓扑分析获得清热活血方治疗类风湿性关节炎的关键靶点113个,GO分析共获得生物过程、分子功能、细胞组分共479个富集结果。KEGG富集表明清热活血方可能通过MAPK、Estrogen、PI3K-AKT、Thyroid hormone、Neurotrophin、HIF-1、ErbB、FoxO、B cell receptor等通路干预RA。拓扑得到CULI、EP300、HSP90AA1、TP53、HSPA8、CDC5L、UBC、RPS27A共8个干预RA的Hub节点。结论:清热活血方可能通过多靶点、多通路进行调控,达到治疗类风湿性关节炎的作用。     

慢性再生障碍性贫血中西医结合优化治疗方案临床研究

目的评价补肾方联合雄激素及免疫抑制剂治疗慢性再生障碍性贫血（CAA）的临床疗效,以确立中西医结合治疗CAA的优化治疗方案。方法将39例CAA患者随机分为3组,对照组（16例）采用司坦唑醇片联合环孢素A（CsA）,试验一组（11例）辨证采用补肾Ⅰ、Ⅱ、Ⅲ号方治疗,试验二组（12例）在对照组基础上加用补肾Ⅰ、Ⅱ、Ⅲ号方治疗,疗程6个月。分别观察各组临床疗效及治疗前后患者外周血清促红细胞生成素（EPO）、干扰素-γ（IFN-γ）水平的变化情况。结果 3组在临床疗效、外周血象改善方面差异无统计学意义（P〉0.05）,但试验二组在贫血症状及中医证候的改善方面明显优于另外2组（P〈0.05）,并能显著降低IFN-γ水平（P〈0.05）。结论补肾方联合雄激素及免疫抑制剂治疗CAA在临床疗效、改善症状及提高血常规计数方面均优于单用中药或单用西药治疗。     

权重配方模型的非线性混合效应分析:一个药物相互作用研究实例

目的:基于权重配方模型,采用非线性混合效应分析(NONMEM),对尿囊素、甲硝唑及地塞米松联合抗炎作用的组方合理性进行定量评价,结果与原算法比较。方法:实验数据为昆明种小鼠组织纤溶酶原激活物(t-PA)样品于405nm处的吸光度值,以权重配方模型为基本模型,组方间相互作用为固定效应,并考虑随机效应,通过NONMEM法建立最终模型,定量评价尿囊素、甲硝唑和地塞米松的联合抗炎作用及其交互作用。结果:基于整体效应的权重配方模型建立成功(P<0.001),X1X2(X1尿囊素,X2地塞米松)作为固定效应加入模型,最终模型中甲硝唑对整体药效作用不明显,尿囊素与地塞米松存在较强协同作用,都是主要起效组分,最优剂量配比尿囊素∶甲硝唑∶地塞米松=400∶131∶8.0(mg/kg,i.p.)。结论:采用NONMEM法,可全面考虑各组分间交互作用及个体间和个体内误差等随机效应,使权重配方模型更加严谨,与原算法比较,提供的信息量更大。     

疏筋解毒方对PD大鼠黑质纹状体Bcl－2／BaxmRNA表达的影响

目的观察疏筋解毒方对帕金森病（PD）大鼠中脑黑质Bcl-2mRNA／BaxmRNA表达的影响,研究其对PD治疗作用的可能机制。方法采用6-羟多巴胺（6-OHDA）建立PD大鼠模型,应用原位杂交分子生物学技术,检测PD大鼠黑质纹状体Bcl－2mRNA／BaxmRNA分布及表达。结果疏筋解毒方有提高PD大鼠中脑Bcl-2mRNA／BaxmRNA分布及表达的趋势。结论疏筋解毒方可能在基因调控层面。通过提高Bcl-2mRNA／BaxmRNA比率,达到抑制PD大鼠中脑多巴胺能神经元凋亡。     

益气活血方对实验性高脂血症大鼠血脂及载脂蛋白的影响

日的观察益气活血对高脂血症动物模型血清中TC、TG、LDL—CxHDL—c、ApoAI、ApoB100的含量的影响,探讨益气活血法在治疗高脂血症中的作用及各项指标的变化与剂量之间的关系。方法选SD大鼠60只,随机分为六组,造高脂血症模型后,分别给予益气活血方高、中、低剂量及非诺贝特治疗,从腹主动脉取血,检测TC、TG、LDL—c、HDL—c、ApoAI、ApoB100的含量。结果益气活血方能显著降低大鼠血清中TG、TC、LDL—c、APOB100水平,显著提高大鼠血清中HDL—C和APOAI水平,并有一定的量效关系。     

通里攻下法对胆囊神经-Cajal间质细胞-平滑肌网络损伤防治作用研究

目的:观察豚鼠胆囊神经-Caja间质细胞-平滑肌网络在结石性胆囊炎时的形态学变化,探讨通里攻下方剂防治胆石症的机制。方法:将50只豚鼠随机分为对照组、模型组和防治组,采用免疫荧光标记和共聚焦显微镜,对比观察各组豚鼠胆囊神经-Caja间质细胞-平滑肌网络形态学变化。结果:模型组较对照组胆囊神经-Caja间质细胞-平滑肌网络结构不完整,Cajal细胞荧光强度明显减少(P<0.05),治疗组较模型组胆囊神经-Caja间质细胞-平滑肌网络结构完整。结论:结石性胆囊炎时,胆囊神经-Caja间质细胞-平滑肌网络损伤明显,通里攻下方剂对胆囊神经-Caja间质细胞-平滑肌网络的保护作用为其防治胆石症的机制之一。     

开郁清热方改善胰岛功能的临床研究

目的验证开郁清热方改善胰岛功能的临床疗效。方法选取仝小林教授于广安门医院门诊诊治的2型糖尿病病历116例,所有患者辨证均属于肝郁胃热证,给予中药开郁清热方治疗,于治疗前、治疗后3个月、6个月、1年、1年半、2年分别记录其空腹血糖（FPG）、餐后2h血糖（2hPG）、胰岛素等检查指标,并根据公式计算患者胰岛功能指数（HOMA-β）,运用统计软件SPSS16．0对数据进行分析。结果治疗后各组空腹血糖、餐后2h血糖均较治疗前有明显下降（P〈0．05）,而治疗后各组间空腹血糖、餐后2h血糖比较,差异无统计学意义（P〉0．05）;HOMA-β均有一定程度的下降,但治疗前、治疗后比较,差异无统计学意义（P〉0．05）。结论开郁清热方具有一定的胰岛功能保护作用。     

Evolutionary-driven support vector machines for determining the degree of liver fibrosis in chronic hepatitis C

Objective

Hepatic fibrosis, the principal pointer to the development of a liver disease within chronic hepatitis C, can be measured through several stages. The correct evaluation of its degree, based on recent different non-invasive procedures, is of current major concern. The latest methodology for assessing it is the Fibroscan and the effect of its employment is impressive. However, the complex interaction between its stiffness indicator and the other biochemical and clinical examinations towards a respective degree of liver fibrosis is hard to be manually discovered. In this respect, the novel, well-performing evolutionary-powered support vector machines are proposed towards an automated learning of the relationship between medical attributes and fibrosis levels. The traditional support vector machines have been an often choice for addressing hepatic fibrosis, while the evolutionary option has been validated on many real-world tasks and proven flexibility and good performance.

Methods and materials

The evolutionary approach is simple and direct, resulting from the hybridization of the learning component within support vector machines and the optimization engine of evolutionary algorithms. It discovers the optimal coefficients of surfaces that separate instances of distinct classes. Apart from a detached manner of establishing the fibrosis degree for new cases, a resulting formula also offers insight upon the correspondence between the medical factors and the respective outcome. What is more, a feature selection genetic algorithm can be further embedded into the method structure, in order to dynamically concentrate search only on the most relevant attributes. The data set refers 722 patients with chronic hepatitis C infection and 24 indicators. The five possible degrees of fibrosis range from F0 (no fibrosis) to F4 (cirrhosis).

Results

Since the standard support vector machines are among the most frequently used methods in recent artificial intelligence studies for hepatic fibrosis staging, the evolutionary method is viewed in comparison to the traditional one. The multifaceted discrimination into all five degrees of fibrosis and the slightly less difficult common separation into solely three related stages are both investigated. The resulting performance proves the superiority over the standard support vector classification and the attained formula is helpful in providing an immediate calculation of the liver stage for new cases, while establishing the presence/absence and comprehending the weight of each medical factor with respect to a certain fibrosis level.

Conclusion

The use of the evolutionary technique for fibrosis degree prediction triggers simplicity and offers a direct expression of the influence of dynamically selected indicators on the corresponding stage. Perhaps most importantly, it significantly surpasses the classical support vector machines, which are both widely used and technically sound. All these therefore confirm the promise of the new methodology towards a dependable support within the medical decision-making.     

The Rewarming Index Formula for Pediatric Cardiopulmonary Perfusion

Careful rewarming of perfusion blood following cardiopulmonary bypass surgery is critical to a successful outcome, but the optimal rewarming strategy is not clear. The purpose of this study was to derive a formula for a rewarming index (defined as [rewarming time × perfusion flow]/[body weight × body surface area]) that would enable the calculation of the ideal rewarming conditions for pediatric cardiopulmonary perfusion. We retrospectively investigated 220 pediatric cardiopulmonary bypass operations conducted from July 2005 to June 2008 in Okayama University Hospital, Japan. We determined the formula as Φ = (T × Q)/(R × S) = |0.9127P ? 0.0152|, where Φ = rewarming index, T = rewarming time (min), Q = perfusion volume (L), R = body weight (kg), S = body surface area (m²), and P = temperature gap (). The formula will help those who perform pediatric cardiopulmonary bypass surgery to establish ideal perfusion flow conditions and to control physiological temperature during rewarming.     

HPLC测定肉桂配方颗粒中的桂皮醛和桂皮酸

目的 建立测定肉桂配方颗粒中桂皮醛和肉桂酸含量的方法.方法 采用HPLC法,色谱柱为Hydrosphere C_(18)(250mm×4.6 mn,5 μm),流动相为乙腈-水-0.1%磷酸溶液(35:25:40),流速为1.0 mL·min~(-1),检测波长为287 nm.结果 桂皮醛的线性范围为0.75～7.50μg(r=0.9995),平均回收率为98.2%(RSD=1.61%);肉桂酸的线性范围为0.22～1.32μg(r=0.9992),平均回收率为97.9%(RSD=1.32%).结论 所建方法简便、灵敏、准确,专属性较强,可有效地控制肉桂配方颗粒的质量.