浅议《中药药理学(供中西医结合专业用)》之编、教、学、用

《中药药理学（供中西医结合专业用）》突破以往教材的模式,将中药分为辨证治本、祛因治病、对症指标３类,辨病与辨证结合,对中西医结合理论的理解、教、学及研发应用都有着积极的启迪和指导作用。     

理中汤、人参皂苷Rg1、6-姜酚对Caco-2细胞PepT1转运功能影响的比较

目的:观察比较理中汤、人参皂苷Rg1、6-姜酚对Caco-2细胞肽转运载体PepT1转运二肽的能力及其蛋白、mRNA表达的影响。方法:Caco-2细胞融合后连续培养28d后分别给予理中汤、人参皂苷Rg1、6-姜酚处理,并设立正常对照组及cAMP抑制剂对照组,用放射性同位素示踪技术比较Caco-2细胞转运二肽化合物Glycyl-Sarcosine的能力,采用westernblot方法测定Caco-2细胞膜上PepT1蛋白的表达,荧光定量PCR方法测定PepT1mRNA(SLC15A1)的表达水平。结果:理中汤、人参皂苷Rg1及6-姜酚均在不同程度上表现为促进Caco-2细胞转运Glycyl-Sarcosine的作用;Caco-2细胞经理中汤/人参皂苷Rg1/6-姜酚处理24h后,细胞膜PepT1蛋白表达水平均明显增高。6-姜酚能明显上调Caco-2细胞SLC15A1表达,人参皂苷对Caco-2细胞SLC15A1表达的作用表现为下调,理中汤对Caco-2细胞SLC15A1表达作用不明显。且理中汤、人参皂苷Rg1、6-姜酚三者作用各有特点。结论:理中汤及其成分人参皂苷Rg1、6-姜酚具有促进正常培养Caco-2细胞转运二肽化合物Glycyl-Sarcosine的作用,该过程调控与胞内第二信使cAMP有一定的关系。     

道家异方术袁氏按导源流释要

失眠又称不寐,是以经常不得安睡为特征的一种症候.临床表现不一,有难以入寐,有寐而易醒,有彻夜不寐等.顽固性的失眠,经常伴有头痛、健忘、怔忡等症.祖国医学认为失眠与心脾肝肾以及阴血不足有关,痰热宿食,上扰心神以致卧不得安.     

参芪复方对糖尿病大血管病变GK大鼠PI3-K/Akt信号通路的影响

目的探讨参芪复方防治糖尿病大血管病变的作用机制。方法以Wistar大鼠18只作为空白组,73只GK大鼠随机分为4组:GK组18只、模型组19只、阿托伐他汀组18只、参芪复方组18只。模型组、阿托伐他汀组、参芪复方组给予一氧化氮合酶(NOS)抑制剂L-NAME0.1mg/(ml.d),加入饮用水中进行糖尿病大血管病变造模,造模同时开始给药。35天后观测主动脉形态,检测血清C反应蛋白(CRP)含量和腹主动脉PI3-KP85a、AktmRNA表达量变化情况。结果参芪复方中药可减轻模型大鼠动脉粥样硬化的病理改变程度,降低血清CRP水平(P<0.01);参芪复方组PI3-KP85amRNA表达水平低于模型组,但无统计学意义;与模型组比较,参芪复方组能明显降低腹主动脉血管壁AktmRNA表达水平(P<0.01)。结论参芪复方可有效防治糖尿病大血管病变的发生发展,其机制可能与抑制糖尿病GK大鼠主动脉血管壁AktmRNA表达量,抑制PI3-K/Akt信号通路有关。     

MicroRNA regulation of cancer stem cells

Cancer stem cells (CSC), or cancer cells with stem cell properties, have been reported in many human tumors and are thought to be responsible for tumor initiation, therapy resistance, progression, relapse, and metastasis. Despite their potential clinical importance, how CSCs are regulated at the molecular level is not well understood. MicroRNAs (miRNA), small noncoding RNAs that play critical roles in normal stem cell functions during development, have emerged as important regulators of CSCs as well. In this review, we summarize the current major findings of miRNA regulation of various CSCs and discuss our recent findings that miR-34a suppresses prostate CSCs and metastasis by directly repressing CD44. This recent progress has important implications for understanding how CSCs are intricately regulated by networks of miRNAs and for developing novel mechanism-based miRNA therapeutics that specifically target CSCs.     

Proliferating macrophages associated with high grade, hormone receptor negative breast cancer and poor clinical outcome

Macrophages, a key cell in the inflammatory cascade, have been associated with poor prognosis in cancers, including breast cancer. In this study, we investigated the relationship of a subset of macrophages??proliferating macrophages (promacs)??with clinico-pathologic characteristics of breast cancer, including tumor size, grade, stage, lymph node metastases, hormone receptor status, subtype, as well as early recurrence, and survival. This study included a discovery and validation set that was conducted at two institutions and laboratories (University of California, San Francisco and University of Chicago) using two independent cohorts of patients with breast cancer. Formalin-fixed, paraffin-embedded sections and/or tissue microarrays were double-stained with anti-CD68 (a macrophage marker) and anti-PCNA (a proliferation marker) antibodies. The presence of intratumoral promacs was significantly correlated with high grade, hormone receptor negative tumors, and a basal-like subtype. In contrast, there was no correlation between promacs and tumor size, stage, or the number of the involved lymph nodes. These findings were consistent between the two study cohorts. Finally, promac numbers were a significant predictor of recurrence and survival. In the pooled analysis, elevated promac levels were associated with a 77% increased risk of dying (P?=?0.015). The presence of promacs in human breast cancer may serve as a prognostic indicator for poor outcomes and early recurrence and serve as a potential cellular target for novel therapeutic interventions.     

致康胶囊用于计划生育手术后的疗效观察

目的：探讨致康胶囊用于计划生育手术后止血、止痛的疗效。方法：对施行计划生育手术的患者420例进行前瞻性研究,观察组210例术后口服致康胶囊,对照组210例术后口服左氧氟沙星片,人工流产术后增加服用益母草胶囊,放置宫内节育器术后加服安络血片。结果：治疗组术后出血天数显著少于对照组,术后出血量显著少于对照组,术后腹痛发生率显著低于对照组,均P〈0.05。结论：致康胶囊有良好的止血、止痛、消炎作用,是计划生育手术后的理想药物。     

Complement C3 and cleavage products in cardiometabolic risk

This review summarizes available evidence on the role of serum complement component 3 (C3), produced by liver, adipocytes and activated macrophages at inflammation sites, and C3 cleavage products linking lipoproteins and metabolism to immunity. C3 and cleavage products are modified in several associated metabolic disorders including obesity, insulin resistance, type-2 diabetes, dyslipidemia, and cardiovascular diseases. Circulating C3 is independently and linearly associated with serum triglycerides, C-reactive protein (CRP), waist circumference and in some populations inversely with current smoking. The complement cascade is activated during myocardial ischemia and likely mediates immune and inflammatory responses in ischemic myocardium. Serum complement activation is elevated in unstable rather than stable angina pectoris suggesting added contribution to damage extension in acute coronary syndromes. In logistic regression models for incident metabolic syndrome (MetS), increasing C3 concentrations predicted MetS in women, after adjusting for continuous values of 3 major MetS components and other confounders, with a relative risk similar in magnitude to an established component suggesting elevated C3 likely constitutes part of the cluster of MetS in women. C3 interacts with MetS in men for independently conferring risk of incident type-2 diabetes and coronary heart disease (CHD). In women, though C3 is equally predictive of cardiometabolic risk, it is less so additively to MetS components or to CRP. Evidence suggests that circulating C3 might serve as a signal for an immune process that enhances - via mediation of increased apolipoprotein (apo) E levels - the development of dysfunctional apoA-I particles rendering them diabetogenic and atherogenic in populations prone to MetS or subsets of populations harboring impaired glucose tolerance. C3 activation also leads to production of chemoattractants C3a and C5a, and acylation stimulating protein (ASP, C3adesArg), a lipogenic hormone, which contribute additionally to the metabolic phenotypes generated. These observations have clinical and public health implications.     

1,3,8-Triazaspiro[4.5]decane-2,4-diones as efficacious pan-inhibitors of hypoxia-inducible factor prolyl hydroxylase 1-3 (HIF PHD1-3) for the treatment of anemia

The discovery of 1,3,8-triazaspiro[4.5]decane-2,4-diones (spirohydantoins) as a structural class of pan-inhibitors of the prolyl hydroxylase (PHD) family of enzymes for the treatment of anemia is described. The initial hit class, spirooxindoles, was identified through affinity selection mass spectrometry (AS-MS) and optimized for PHD2 inhibition and optimal PK/PD profile (short-acting PHDi inhibitors). 1,3,8-Triazaspiro[4.5]decane-2,4-diones (spirohydantoins) were optimized as an advanced lead class derived from the original spiroindole hit. A new set of general conditions for C-N coupling, developed using a high-throughput experimentation (HTE) technique, enabled a full SAR analysis of the spirohydantoins. This rapid and directed SAR exploration has resulted in the first reported examples of hydantoin derivatives with good PK in preclinical species. Potassium channel off-target activity (hERG) was successfully eliminated through the systematic introduction of acidic functionality to the molecular structure. Undesired upregulation of alanine aminotransferese (ALT) liver enzymes was mitigated and a robust on-/off-target margin was achieved. Spirohydantoins represent a class of highly efficacious, short-acting PHD1-3 inhibitors causing a robust erythropoietin (EPO) upregulation in vivo in multiple preclinical species. This profile deems spirohydantoins as attractive short-acting PHDi inhibitors with the potential for treatment of anemia.