Preparation and characterization of paclitaxel palmitate albumin nanoparticles with high loading efficacy: an in vitro and in vivo anti-tumor study in mouse models

BackgroundCombination of the prodrug technique with an albumin nano drug-loaded system is a novel promising approach for cancer treatment. However, the long-lasting and far-reaching challenge for the treatment of cancers lies in how to construct the albumin nanometer drug delivery system with lead compounds and their derivatives.MethodsIn this study, we reported the preparation of injectable albumin nanoparticles (NPs) with a high and quantitative drug loading system based on the Nab^TM technology of paclitaxel palmitate (PTX-PA).ResultsOur experimental study on drug tissue distribution in vivo demonstrated that the paclitaxel palmitate albumin nanoparticles (Nab-PTX-PA) remained in the tumor for a longer time post-injection. Compared with saline and paclitaxel albumin nanoparticles (Abraxane^®), intravenous injection of Nab-PTX-PA not only reduced the toxicity of the drug in normal organs, and increased the body weight of the animals but maintained sustained release of paclitaxel (PTX) in the tumor, thereby displaying an excellent antitumor activity. Blood routine analysis showed that Nab-PTX-PA had fewer adverse effects or less toxicity to the normal organs, and it inhibited tumor cell proliferation more effectively as compared with commercial paclitaxel albumin nanoparticles.ConclusionsThis carrier strategy for small molecule drugs is based on naturally evolved interactions between long-chain fatty acids (LCFAs) and Human Serum Albumin (HSA), demonstrated here for PTX. Nab-PTX-PA shows higher antitumor efficacy in vivo in breast cancer models. On the whole, this novel injectable Nab-PTX-PA has great potential as an effective drug delivery system in the treatment of breast cancer.     

中国女性乳腺癌群体筛查与机会性筛查的比较研究

目的比较乳腺癌群体筛查和机会性筛查两种模式的人群特点、筛查阳性率、乳腺癌检出率、早期乳腺癌比例及筛查费用。方法本研究为前瞻性多中心队列研究,研究时间为2014年1月1日至2016年12月31日。分别入组群体筛查和机会性筛查受试者,填写调查问卷表,并进行每年1次乳腺体检及乳腺超声检查,共完成3轮筛查,采用χ²检验、Fisher确切概率法和Wilcoxon秩和检验比较两组人群的特点及筛查结果。结果共入组受试者20080人。群体筛查组完成3轮筛查的人数分别为9434人(100%)、8111人(85.98%)和3940人(41.76%);机会性筛查组分别为10646人(100%)、6209人(58.32%)和2988人(28.07%)。机会性筛查组中产后哺乳时间<3个月(1275/9796比1061/8860,χ²=4.597,P=0.032)、未生育(850/10646比574/9434,χ²=27.400,P<0.01)、有流产史(6384/10646比5062/9434,χ²=81.232,P<0.01)、绝经后(2776/10646比2217/9434,χ²=17.757,P<0.01)、口服避孕药>6个月(171/10646比77/9434,χ²=25.593,P<0.01)及一级亲属乳腺癌阳性家族史(464/10646比236/9434,χ²=51.257,P<0.01)比例高于群体筛查组。机会性筛查组筛查阳性率(514/10646比128/9434,χ²=194.736,P<0.01)、乳腺癌检出率(158/10646比13/9434,χ²=107.374,P<0.01)和活检阳性率(158/452比13/87,χ²=13.491,P<0.01)高于群体筛查组。群体筛查组早期乳腺癌(0期和Ⅰ期)比例高于机会性筛查组(10/12比66/141,χ²=5.902,P=0.015)。群体筛查组发现每1例乳腺癌的平均费用为215038元,是机会性筛查组15799元的13.6倍。机会性筛查组基层医院的活检阳性率低于大型医院(79/267比79/185,χ²=8.267,P=0.004),而群体筛查组两者无明显差异(6/37比7/50,χ²=0.082,P=0.774)。结论乳腺癌筛查可以早期发现乳腺癌。机会性筛查具有受试者乳腺癌高危因素比例高、筛查阳性率高、乳腺癌检出率高、活检阳性率高、筛查费用低的特点。但是,机会性筛查的早期乳腺癌比例低于群体筛查,基层医院开展机会性筛查时活检阳性率较低。两种筛查模式各有优势,需要有机结合,取长补短。     

内蒙古自治区中(蒙)药材种植统计数据挖掘分析

目的:中(蒙)药材作为中国独特的健康资源,在经济社会发展中发挥着重要作用,充分挖掘中(蒙)药材种植统计数据,为内蒙古自治区中(蒙)药材种植及发展提供理论依据。方法:运用空间自相关分析方法和地理探测器,对内蒙古自治区各旗县中(蒙)药材种植面积及种类的空间分布特征进行分析。结果:内蒙古自治区各旗县中(蒙)药材种植面积和种植种类在空间上差异很大,并且中(蒙)药材种植与其生境特征有着密切关系。结论:目前内蒙古自治区中(蒙)药材产业发展受环境、市场、技术和经营体制的多重制约,应发挥地方资源优势,根据地域区间差异性和区内相似性,找出中(蒙)药材适宜的种植地区。     

A Summary and Evaluation of Current Evidence for Myocardial Infarction with Chinese Medicine

Objective: To provide evidence-based recommendations for clinical application and provoke thoughts for future researchers by conducting a comprehensive summary and evaluation of the current evidence profile for the role of Chinese medicine(CM) in treating myocardial infarction(MI). Methods: Online databases including Pub Med, EMBase, Cochrane Library, Chinese National Knowledge Infrastructure(CNKI), Chinese Biomedical Medicine(CBM), VIP Journal Integration Platform, and Wanfang database were systematically searched for literatures on CM in treating MI. After screening, studies were categorized into 5 types, i.e. systematic review(SR), randomized controlled trial(RCT), observational study, case report and basic research. General information was abstracted, and the quality levels of these studies and their conclusions were summarized and assessed. Results: A total of 452 studies including 10 SRs, 123 RCTs, 47 observational studies, 28 case reports, and 244 basic researches were selected. Clinical studies centered primarily on herbal decoction and mostly were not rigorously performed. High-quality studies were predominantly on Chinese patent medicines(CPMs) such as Danshen Injection(丹参注射液), Shenmai Injection(参麦注射液), Shengmai Injection(生脉注射液) and Qishen Yiqi Dripping Pills(芪参益气滴丸). The most frequently observed pattern of drug combination was decoction plus injection. Results of SRs and clinical studies showed that CM may reduce mortality, decrease risk of complication, reduce myocardial injury, improve cardiac function and inhibit ventricular remodeling. Findings from basic researches also supported the positive role of CM in reducing infarct size and myocardial injury, promoting angiogenesis, preventing ventricular remodeling and improving cardiac function. According to the current evidence body, CM has proven effects in the prevention and treatment of MI. It is also found that the effects of CPMs vary with indications. For instance, Shenmai Injection has been found to be especially effective for reducing the incidence of acute clinical events, while CPMs with qi-nourishing and bloodcirculating properties have been proven to be effective in inhibiting ventricular remodeling. High quality evidence supports the use of CM injection for acute MI and CPM for secondary prevention. Reports on adverse events and other safety outcomes associated with CM for MI are scarce. Conclusions: Sufficient evidence supported the use of CM as an adjuvant to Western medicine for preventing and treating MI. The choice of drug use varies with disease stage and treatment objective. However, the quality of the evidence body remains to be enhanced.     

Local injection of bone-marrow derived mesenchymal stromal cells alters a molecular expression profile of a contact frostbite injury wound and improves healing in a rat model

IntroductionFrostbite is a traumatic injury of the tissues upon low temperature environment exposure, which is characterized by direct cell injury due to freezing-thawing followed by development of an acute inflammatory process. Severe frostbite can lead to necrosis of soft tissues and loss of a limb. Mesenchymal stromal cells (MSCs) have a unique ability to modulate pathogenic immune response by secretion of paracrine factors, which suppress inflammation and mediate more efficient tissue regeneration. It should be noted that potential of stem cell therapy for frostbite injury treatment has not been investigated so far. Here, we evaluated a healing capacity of bone-marrow derived MSCs for the treatment of contact frostbite injury wound in a rat model.MethodsCold-contact injury in a Wistar rat model was induced by 1-minute tight application of the cooled probe (?196 ?C) to the skin surface of the left hip. Rat bone marrow MSCs were phenotypically characterized and used for local injections into non-damaged tissues surrounding the wound of animals from the experimental group. The second group of rats was treated in the same manner with 1 mL of isotonic sodium chloride solution. Analysis of cytokine and growth factor expression profile in сold-contact injury wounds was performed on days 5, 9, and 16 using immunoblotting and enzyme-linked immunosorbent assay. Animal recovery in MSC-treated and vehicle-treated groups was evaluated by several criteria including body weight recording, determination of eschar desquamation and re-epithelialization terms, assessment of wound closure kinetics, and histological scoring of the wounds on day 23.ResultsIt turned out that a single subcutaneous administration of MSCs around the wound site resulted in elevated expression of pro-survival and pro-angiogenic VEGF-A and PDGF and 3–5-fold decrease in pro-inflammatory IL-1β as compared with the frostbite wound treated with a vehicle. Moreover, treatment with MSCs caused accelerated wound re-epithelialization (p < 0.05) as well as a better histological score of the MSC-treated wounds.ConclusionsThus, our data suggested that the use of MSCs is a promising therapeutic strategy for the treatment of cold-induced injury wounds.     

参芪养心颗粒对冠脉结扎致犬急性心肌缺血影响的实验研究

[目的]研究参芪养心颗粒对冠脉结扎致犬急性心肌缺血的影响。[方法]冠脉结扎致犬急性心肌缺血,观察参芪养心颗粒对犬心肌缺血区心外膜电图（N-ST）、冠脉血管阻力（CVR）、心肌血流量（MBF）、心肌耗氧量（MOC）、左心室心肌细胞苏木精-伊红（HE）染色病理变化以及心肌梗死区质量的影响。[结果]与模型对照组比较参芪养心颗粒中剂量组（5.46 g生药/kg）和参芪养心颗粒高剂量组（10.92 g生药/kg）可显著降低犬心肌缺血区N-ST。与模型对照组比较参芪养心颗粒中剂量组（5.46 g生药/kg）和参芪养心颗粒高剂量组（10.92 g生药/kg）可显著降低冠脉血管阻力。与模型对照组比较参芪养心颗粒中剂量组（5.46 g生药/kg）和参芪养心颗粒高剂量组（10.92 g生药/kg）可显著增加犬急性心肌缺血模型的心肌血流量。与模型对照组比较参芪养心颗粒高剂量组（10.92 g生药/kg）可显著降低心肌耗氧量。与模型对照组比较参芪养心颗粒中剂量组（5.46g生药/kg）和参芪养心颗粒高剂量组（10.92 g生药/kg）可显著降低心肌梗死区质量。[结论]参芪养心颗粒对冠脉结扎致犬急性心肌缺血模型具有保护作用。     

New inhibitors of nitric oxide production from the seeds of Myristica fragrans

Six dihydrobenzofuran type neolignans were isolated from the dried ripe seeds of Myristica fragrans Houtt. (family: Myristicaceae) and their chemical structures were identified as licarin B (1), 3′-methoxylicarin B (2), myrisfrageal A (3), isodihydrocainatidin (4), dehydrodiisoeugenol (5), and myrisfrageal B (6), respectively, on the basis of spectroscopic data analyses. Among them, compounds 3 and 6 are new compounds. Compounds 1–6 showed inhibition of nitric oxide production in lipopolysaccharide-activated murine monocyte-macrophage RAW264.7 with IC₅₀ values of 53.6, 48.7, 76.0, 36.0, 33.6, and 45.0 μM, respectively. These values were compared to those of the positive controls, indomethacin and L-N⁶-(1-iminoethyl)-lysine, which have IC₅₀ values of 65.3 and 27.1 μM, respectively. Further compounds 3, 5 and 6 suppressed LPS-induced iNOS mRNA expression in a does-dependent manner in RAW 264.7 cells assayed by real-time RT-PCR. Compounds 3, 5 and 6 may inhibit NO overproduction via inhibition of iNOS mRNA expression. The results provided valuable information for further investigation of compounds 1–6 as anti-inflammatory and chemopreventive agents.     

White matter integrity affected by depressive symptoms in migraine without aura: a tract‐based spatial statistics study

Previous studies have proven that migraine and depression are bidirectionally linked. However, few studies have investigated white matter (WM) integrity affected by depressive symptoms in patients suffering from migraine without aura (MWoA). Forty patients with MWoA were divided into two groups according to their self‐rating depression scale (SDS) score in the present study, including 20 in the SDS (+) (SDS > 49) group and 20 in the SDS (?) (SDS ≤ 49) group. Forty healthy participants were also recruited as the control group. Tract‐based spatial statistics analyses with multiple diffusion tensor imaging‐derived indices [fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD)] were employed collectively to investigate WM integrity between all patients with MWoA and all healthy controls, between each subgroup (SDS (?) group and SDS (+) group) and healthy controls, and between the SDS (?) and SDS (+) groups. Compared with healthy controls, decreased AD was shown in several WM tracts of the whole MWoA group, SDS (?) group and SDS (+) group. In addition, compared with the SDS (?) group, the SDS (+) group showed decreased FA and increased MD and RD, with conserved AD, including the genu, body and splenium of the corpus callosum, bilateral superior longitudinal fasciculi, the right anterior corona radiata and some other WM tracts, similar to previous findings in depression disorder. Furthermore, mean FA and RD in some of the above‐mentioned WM tracts in the SDS (+) group were correlated significantly with SDS scores, including the genu and splenium of the corpus callosum, the right anterior corona radiata and the superior longitudinal fasciculi. Our results suggest that WM integrity may be affected by both depression symptoms (more sensitive as RD) and migraine (more sensitive as AD). The findings may serve as a sensitive biomarker of depression severity in MWoA. Copyright © 2013 John Wiley & Sons, Ltd.     

Cerebral venous sinus thrombosis in Behçet’s disease: a retrospective case-control study

The objective of the study is to investigate the clinical features of Behçet’s disease (BD) complicated with cerebral venous sinus thrombosis (CVST). We retrospectively analyzed the clinical features of age- and gender-matched BD patients with and without CVST. Of the 840 BD patients enrolled, 21 (2.5%, 11 female, mean age 30.3 ± 9.5) were diagnosed as CVST. Eighteen patients (85.7%) developed neurologic manifestations after BD onset, with an average interval of 47.6 months (SD 36.1). Onset of neurologic symptoms was mostly progressive (89.5%), with headache (95.2%) being the most common symptom. Intracranial hypertension occurred in 17 cases (89.5%). Thrombosis was detected mostly in transverse (71.4%) and superior sagittal (66.7%) sinuses, with more frequently (66.7%) dual or multiple sinuses involved. In addition, extra cranial thrombosis was presented in 11 cases. Cerebral infarction was presented in four cases. Compared with BD patients without CVST, the prevalence of extra cranial vascular involvement (52.4 versus 20.6%; P = 0.005) and BDCAF 2006 score (3.7 ± 1.4 versus 1.8 ± 1.3; P = 1.7863 × 10^?7) was higher in BD patients with CVST. During a median 7-month follow-up (range 0.3–88.8 months), 18 patients (85.7%) achieved remission following glucocorticoid, immunosuppressant therapy, anticoagulants, and dehydration, although 3 patients experienced (14.3%) flare. No death was reported. CVST is rare complication of BD and predominately progressively developed in active BD and after BD onset. It typically features intracranial hypertension syndrome and is frequently complicated with extra cranial thrombosis; thus, systemic thrombus screening is highly recommended. Promptly, diagnosis and aggressive treatment are keys to improve the prognosis.     

增殖性糖尿病视网膜病变患者玻璃体液中PEDF与TAOC的关系研究

目的探讨增殖性糖尿病视网膜病变(proliferative diabetic retinopathy,PDR)患者玻璃体液中色素上皮衍生因子(pigment epithelium-derived factor,PEDF)与总抗氧化能力(total anti-oxidant capacity,TAOC)的关系。方法选择行玻璃体切割术的增殖性糖尿病视网膜病变患者20例(20眼),其中PDR合并玻璃体出血组12眼,PDR无玻璃体出血组8眼。非糖尿病患者18例(18眼)作为对照组。采用ELISA方法测定玻璃体液中PEDF和TAOC的水平,并行统计学分析。结果与对照组比较,PDR患者玻璃体液中的TAOC明显降低(P<0.01)。玻璃体液中PEDF水平与TAOC呈正相关(r=0.35,P<0.05),和对照组呈正相关(r=0.39,P<0.05)。无玻璃体出血组PDR患者玻璃体液中PEDF水平与对照组和合并玻璃体出血组比较明显降低(P<0.05)。结论玻璃体液中PEDF水平与TAOC密切相关。PEDF可作为眼内源性抗氧化物并对PDR起到保护作用。