四妙勇安汤方源探析

四妙勇安汤由金银花、玄参、当归、甘草4味药物组成,为《古代经典名方目录(第一批)》中100个经典名方之一。经溯源发现,四妙勇安汤源于《石室秘录》,后由《古今图书集成·医部全录》《验方新编》等书引用。从古代文献记载来看均有方无名,"四妙勇安汤"之名,最早见于1956年《中医治疗动脉栓塞性坏疽症的成效》,是由当时记者吕民报道河北省释迦宝山用"四妙勇安汤"治疗当地的动脉栓塞性坏疽时冠名。四妙勇安汤从方药组成与剂量上看,从《石室秘录》开始即是"金银花三两,当归二两,生甘草一两,玄参三两",历代版本《方剂学》确定四妙勇安汤金银花、玄参、当归、甘草的比例就是3∶3∶2∶1。而查阅文献,释迦宝山临证所用的四妙勇安汤由"玄参132 g,当归99 g,银花66 g,甘草33 g"组成,金银花、玄参、当归、甘草的比例变成2∶4∶3∶1。从治疗时间上看,原方记载的7日愈或是10日愈,而释迦宝山将其用到了三四个月,甚至五六个月。研究认为,古籍中的四妙勇安汤,应该是用于疾病的初期,尽早发现和治疗;而释迦宝山修改过的剂量,是广泛用于脱骨疽的中后期,甚至出现坏疽的严重病情所使用的,因此服药时间长,剂量大。且四妙勇安汤临证不仅限于治疗脱骨疽,也用于大头疮等,现代该方的使用已经大为拓展。相关研究已证实四妙勇安汤具有抗炎、稳定斑块、降脂、保护血管、改善血液流变学、抗凝、抑制血栓形成和促纤溶等作用,后续应开展君臣佐使辨析,对其临床应用范围重新进行界定。     

Elevated serum levels of Interleukin‐37 are associated with inflammatory cytokines and disease activity in rheumatoid arthritis

Interleukin‐37 (IL‐37) is closely associated with several inflammatory diseases. However, the role of IL‐37 in the pathogenesis of rheumatoid arthritis (RA) remains unclear. The aim of this study was to assess the associations between serum levels of IL‐37 and disease activity, inflammatory cytokines, and bone loss in patients with RA. Serum cytokines levels were examined by Enzyme‐linked immunosorbent assay (ELISA). Radiographic bone erosion was assessed using the van der Heijde‐modified Sharp score and bone mineral density (BMD) was measured using DXA. Serum IL‐37 levels in RA patients were significantly higher than those in HCs (p < 0.001), and were significantly positively correlated with clinical parameters of disease activity and serum levels of IL‐17 and IL‐23. In addition, serum IL‐37 levels were significantly higher in patients with stage IV of radiographic bone erosion than those with stage III and stage I–II, and they were significantly higher in those with osteopenia and osteoporosis than in those with normal BMD. Our results suggest that serum IL‐37 levels were increased in patients with RA and were positively associated with disease activity, IL‐17/IL‐23 and bone loss in RA, suggesting that IL‐37 may play a critical role in the pathogenesis of RA.     

磁共振弥散加权成像结合三维乳腺数字化断层摄影钙化分数在乳腺良恶性钙化病变鉴别中的诊断价值

  目的  评估磁共振弥散加权成像（DWI）结合三维乳腺数字化断层摄影（DBT）钙化分数对于钙化征象在乳腺良恶性病变诊断的应用价值。  方法  回顾性分析我院118例行乳腺DWI检查和DBT检查的患者，DBT检查发现有钙化征象，其中乳腺癌患者51例，病理类型包括:浸润性导管癌、浸润性导管癌、导管原位癌、髓样癌、浸润性小叶癌、黏液腺癌；乳腺良性病变67例，病理类型包括:纤维腺瘤、腺病、导管内乳头状瘤。对所有患者DBT图像的钙化征象进行钙化评分并且测量相应病变区域的表观扩散系数（ADC）值，分析ADC值、钙化分数及二者联合在乳腺含钙化病变的诊断效能。  结果  乳腺癌组ADC值低于乳腺良性病变组，差异有统计学意义（P < 0.05）；钙化分数高于良性病变组，差异有统计学意义（P < 0.05）。ADC值对诊断乳腺良恶性病变的曲线下面积（AUC）为0.853，钙化分数对诊断乳腺良恶性病变的AUC值为0.855，采用Delong检验得出两种方法对诊断乳腺含钙化病变的良恶性诊断效能一致，差异无统计学意义（P=0.625）。两种方法（钙化分数+ADC值）的Logistic回归分析显示，两种方法相结合的AUC值为0.903，具有很高的诊断效能。将ROC曲线（钙化分数、ADC值、两种方法结合的预测概率）经两两Delong检验结果显示，两种方法结合的ROC与单一ROC的差异有统计学意义（P=0.041、0.022）。  结论  DWI与DBT钙化分数对于钙化征象在乳腺良恶性病变的鉴别诊断效能无差别，两种方法相结合的诊断效能显著高于单一方法，为乳腺含钙化病灶的诊断与鉴别诊断中提供了更加可靠的依据。      

Computer-aided design of dry powder inhalers using computational fluid dynamics to assess performance

Dry powder inhalers (DPIs) are gaining popularity for the delivery of drugs. A cost effective and efficient delivery device is necessary. Developing new DPIs by modifying an existing device may be the simplest way to improve the performance of the devices. The aim of this research was to produce a new DPIs using computational fluid dynamics (CFD). The new DPIs took advantages of the Cyclohaler® and the Rotahaler®. We chose a combination of the capsule chamber of the Cyclohaler® and the mouthpiece and grid of the Rotahaler®. Computer-aided design models of the devices were created and evaluated using CFD. Prototype models were created and tested with the DPI dispersion experiments. The proposed model 3 device had a high turbulence with a good degree of deagglomeration in the CFD and the experiment data. The %fine particle fraction (FPF) was around 50% at 60?L/min. The mass median aerodynamic diameter was around 2.8–4?μm. The FPF were strongly correlated to the CFD-predicted turbulence and the mechanical impaction parameters. The drug retention in the capsule was only 5–7%. In summary, a simple modification of the Cyclohaler® and Rotahaler® could produce a better performing inhaler using the CFD-assisted design.     

马齿苋“成分-活性-中药功效-疾病”研究进展及关联分析

马齿苋是一种药食同源品,具有清热解毒、凉血止血、止痢的功效,为常见中药,作为药物安全性高。马齿苋具有多种活性成分及药理作用,为了充分开发利用马齿苋,加快马齿苋研究的现代化进程,综述马齿苋的研究进展并在此基础上对于其"成分-活性-中药功效-疾病"进行关联分析,为马齿苋的现代化研究提供思路。     

Is dose modification or discontinuation of nilotinib necessary in nilotinib-induced hyperbilirubinemia?

Nilotinib is a specific breakpoint cluster region-Abelson leukemia virus-tyrosine kinase inhibitor that is used as an effective first- or second-line treatment in imatinib-resistant chronic myelogenous leukemia (CML) patients. Hepatotoxicity due to nilotinib is a commonly reported side effect; however, abnormal liver function test (LFT) results have been reported in asymptomatic cases. When alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels are more than five-fold the upper limit of the normal (ULN) or when the serum total bilirubin level is more than three-fold the ULN, dose modification or discontinuation of nilotinib is recommended, resulting in decreased levels of hematological indicators in certain patients with CML. Nilotinib-induced hyperbilirubinemia typically manifests as indirect bilirubinemia without elevated ALT or AST levels. Such abnormal liver functioning is thus not attributed to the presence of a true histologic lesion of the liver. The underlying mechanism may be related to the inhibition of uridine diphosphate glucuronosyltransferase activity. Therefore, nilotinib dose adjustment is not recommended for this type of hyperbilirubinemia, and in the absence of elevated liver enzyme levels or presence of abnormal LFT findings, physicians should consider maintaining nilotinib dose intensity without modifications.