黄芪-莪术药对基于网络药理学的抗大肠癌分子机制

目的:运用计算机网络药理学技术预测黄芪-莪术药对治疗大肠癌的作用靶点和信号通路,进一步分析其抗大肠癌物质基础和作用机制。方法:通过Therapetutic Target Database(TTD),Drugbank数据库收集大肠癌疾病作用靶点;从中药系统药理学分析平台(TCMSP)获得黄芪、莪术所含中药成分;运用Chem Mapper,Pharm Mapper数据库预测所选中药成分作用的疾病靶点;采用Cytoscape软件建立"化合物-疾病靶点"网络模型;利用Clue GO插件对靶点进行基因功能(GO)分析和基于京都基因与基因组百科全书(KEGG)通路富集分析。结果:黄芪-莪术药对活性化合物-大肠癌疾病靶点网络包含56个化合物和54个靶点,关键靶点涉及AMP激活蛋白激酶α1(PRKAA1),前列腺素内过氧化物合酶1(PTGS1),环氧化酶2(PTGS2),胸苷酸合成酶(TYMS),肝羧酯酶1(CES1),血管内皮生长因子B(VEGFB),血管内皮生长因子A(VEGFA),谷胱甘肽S-转移酶P(GSTP1),丝氨酸羟甲基转移酶(gly A)等;靶点的基因功能偏向于肽基酪氨酸的磷酸化,调节细胞外调节蛋白激酶(ERK) 1和ERK2信号串联,内皮细胞凋亡过程的负调节等;重要的KEGG通路涉及癌症通路,Ras信号通路,Rap1信号通路,磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信号通路等。结论:黄芪-莪术药对通过抑制肿瘤细胞增殖分化、促进肿瘤细胞凋亡、抗肿瘤新生血管生成以及增强机体免疫的多表型干预的网络模式产生抗大肠癌活性,其作用信号通路与Ras信号通路,Rap1信号通路,PI3K/Akt信号通路最为相关。     

中药药对治疗糖尿病肾病的药理作用及临床应用研究进展

中药药对是中医临证方剂配伍中画龙点睛之所在,目前关于中药治疗糖尿病肾病的相关研究较多,但主要聚焦在疗效观察和处方总结等方面,缺乏对中药作用机制的深入研究和归纳总结。中药药对与方剂相比化学成分少、组方形式单一、作用机制简单、干扰因素较少等。近年来中医在应用药对治疗糖尿病肾病方面积累了丰富的临床实践经验,不少研究者十分注重组方配伍时药对的应用及其作用规律,通过药对配伍实现多方面的优化组合,进一步提高中药复方的治疗效果。为了明确中药药对治疗糖尿病肾病的作用途径及靶点,本文通过系统地查阅和整理国内外相关文献资料,拟对近10年来经临床观察与动物实验证实对糖尿病肾病确有疗效的,以中医临证分型具有"调补脾肾""利水渗湿""活血化瘀"和"收敛固涩"功效的四类药对的组成规律及现代实验研究现状进行整理分析,总结其配伍原则与药物的化学成分、药代动力学变化及药对各中药不同配伍比例时化学成分的变化规律,以期为上述药对进一步的应用、研究及开发提供参考。     

Drug Release from Film-Coated Chlorpheniramine Maleate Nonpareil Beads: Water Influx and Development of a New Drug Release Model

The purpose of this work was to investigate drug release from film-coated chlorpheniramine maleate (CPM) nonpareils (sugar spheres) and the effect of water influx on the drug release mechanism. The methods used in the study involved the layering of CPM onto nonpareil cores using a fluid-bed apparatus. These CPM cores were then coated with an aqueous ethylcellulose dispersion, which was blended with a solution of hydroxylpropylmethylcellulose (HPMC) at different concentrations. The net water influx was determined by measuring water uptake during dissolution. The film surface area was calculated from bead diameters measured with an optical microscope. Drug release profiles were measured using USP dissolution method I (basket). The results showed that significant water influx occurred, which produced an internal liquid phase ranging from 0 to 1.8 × 10³ mm³/g of sample. As a result of the water uptake, an increase in bead size was observed. The bead surface area varied over the range of 40–80 × 10³ mm²/g sample because of a combined effect of the water uptake and the release of the bead contents. A bead geometry parameter was proposed as the ratio of the bead surface area to the volume of the internal liquid phase. This bead geometry parameter was measured as a function of time and fit to an equation using a computer curve-fitting technique. This equation was substituted into an existing drug release model to give a more appropriate mathematical model describing drug release from this system. The conclusion drawn from these results is that the influx of water during drug dissolution creates a progressive increase in the liquid phase within the nonpareil bead; this causes a corresponding increase in the bead surface area which influences the drug release rate.     

X-连锁低血磷性佝偻病的治疗现状及展望

X-连锁低血磷性佝偻病(XLH)属于遗传性代谢性骨病,发病机制复杂,在临床上较为罕见,其主要临床表现为骨骼畸形及身材矮小,致残率高,因而针对XLH进行及早诊断及治疗对患者康复具有极为重要的意义。传统治疗以补充磷酸盐和维生素D类似物为主,随着学者对XLH病理机制研究逐渐深入,分子靶向治疗等新型治疗方式横空出世,通过多学科联合诊断及治疗的方法为患者带去了福音。本文就XLH的临床特征、发病遗传机制、治疗现状及治疗的未来发展趋势进行综述。     

Perspectives on phytoremediation of zinc pollution in air,water and soil

In this article, we discuss the phytoremediation of Zn pollution in the environment and the mechanism of plant resistance focusing on the mycorrhiza and subcellular mechanisms affecting metal binding and efflux in plants. Phytoremediation is a green low-cost technology that use plants to remove heavy metals (HMs) from soil. As part of this, it is necessary to consider the plant's tolerance to for example zinc (Zn) together with the plant's ability to accumulate and adapt to the specific local environment. During the process of restoring ecosystem contaminations, pH, organic matter, root exudates and microbial biomass affect the efficiency of phytoremediation while considering chemical modification, biosynthesis, microbial assistance and gene technology. However, obstacles remain in terms of for example chemical modifications that may cause either new pollution or disrupt the plant-microorganism symbiosis while other applications such as genetic engineering to change plant traits and function thereby improving heavy metal tolerance and absorption. The selection of gene fragments is complicated and requiring careful considerations due to environmental and human health side effects. Furthermore, using biochar may help to reduce the costs and increase the efficiency of plant phytoremediation. At the same time, there is an urgent need to combine nanotechnology and use of artificial chelating agents and plant hormones to screen the microbiome conducive to plant Zn absorption in order to improve the efficiency of phytoremediation.     

计算机动漫技术展现中医诊治机理探讨

中医不能象现代医学那样,向病家展现疾病发生发展的状态和疾病的实质变化,依中医学的理论和术语解释病情对方听不懂,甚至误认为中医说不清。其实不是说不清,是中医循中国传统文化的认知规律从事诊治活动的本质不为现代人所知、所理解。中医事业的发展需要向社会展现中医诊治的机理,完成这个任务的希望在于借助现代计算机动漫技术。笔者提出这个问题,意在引起中医同仁和计算机动漫专业人员的关注,如果两者结合起来,必将为中医文化的社会化开创一条新路,这是值得思考和实践,而且关系到中医事业前途的大问题。     

Taste masking of ciprofloxacin by ion-exchange resin and sustain release at gastric-intestinal through interpenetrating polymer network

The aim of the study was to taste mask ciprofloxacin (CP) by using ion-exchange resins (IERs) followed by sustain release of CP by forming interpenetrating polymer network (IPN). IERs based on the copolymerization of acrylic acid with different cross linking agents were synthesised. Drug-resin complexes (DRCs) with three different ratios of drug to IERs (1:1, 1:2, 1:4) were prepared & evaluated for taste masking by following in vivo and in vitro methods. Human volunteers graded ADC 1:4, acrylic acid-divinyl benzene (ADC-3) resin as tasteless. Characterization studies such as FTIR, SEM, DSC, P-XRD differentiated ADC 1:4, from physical mixture (PM 1:4) and confirmed the formation of complex. In vitro drug release of ADC 1:4 showed complete release of CP within 60 min at simulated gastric fluid (SGF) i.e. pH 1.2. IPN beads were prepared with ADC 1:4 by using sodium alginate (AL) and sodium alginate-chitosan (AL-CS) for sustain release of CP at SGF pH and followed by simulated intestinal fluid (SIF i.e. pH 7.4). FTIR spectra confirmed the formation of IPN beads. The release of CP was sustain at SGF pH (<20%) whereas in SIF media it was more (>75%). The kinetic model of IPN beads showed the release of CP was non-Fickian diffusion type.     

鲍曼不动杆菌对多黏菌素类抗菌药物耐药现状及机制研究进展

多黏菌素类抗菌药物是多重耐药鲍曼不动杆菌的最后防线，但随着临床对多黏菌素类药物使用增多，鲍曼不动杆菌对其耐药的报道也陆续出现，相关耐药机制的研究成为热点。本文对近年来国内外鲍曼不动杆菌对多黏菌素类耐药报道以及耐药机制研究进行综述，以期对临床合理应用多黏菌素类抗菌药物、保持其抗菌活性提供参考。     

艾灸治疗原发性痛经作用机制研究进展

艾灸治疗原发性痛经应用广泛,通过热效应、光效应、艾烟及药物作用4种起效机制发挥治疗作用,艾灸治疗原发性痛经的机制集中在调节内分泌激素、调节免疫功能、调节神经相关因素、改善子宫微循环等方面,艾灸治疗原发性痛经的机制研究仍存在问题和不足,应当加强艾灸起效机制研究,重视灸法光效应之中的光谱范围及波峰治疗痛经的机制探索,完善艾灸治疗原发性痛经的机制研究,为临床治疗提供实验依据和循证医学证据。     

Extensor Mechanism Reconstruction Using Marlex Mesh: Is Postoperative Casting Mandatory?

BackgroundExtensor mechanism (EM) disruption after total knee arthroplasty is a catastrophic complication. Reconstruction using monofilament polypropylene mesh (Marlex Mesh; CR Bard, Franklin Lakes, NJ) has emerged as the preferred treatment, but reports are limited to the designing institution. This study describes a nondesigner experience and compares 2 postoperative immobilization strategies: long leg cast vs knee immobilizer.MethodsA retrospective review of consecutive EM reconstructions between 2012 and 2019 was performed. Primary repairs and allograft reconstructions were excluded, leaving 33 knees (30 patients) who underwent Marlex reconstruction. Mean time from disruption to reconstruction was 14 months, and 14 of 33 (42%) had previous repair or reconstruction attempts. The mean age was 69 years, and mean body mass index was 35 kg/m². Postoperatively, extension was maintained using a knee immobilizer in 19 of 33 (58%) patients, whereas 14 of 33 (42%) patients were long leg casted. Kaplan-Meier analysis determined all-cause survivorship free of mesh failure.ResultsAt mean 25-month follow-up, 19 of 33 (58%) EM reconstructions were functioning. Excluding explanted infections (5 recurrent and 2 new), 19 of 26 (73%) EM reconstructions were in situ. Six-year survivorship was 69% and not influenced by immobilization type (cast: 67%, immobilizer: 71%; P = .74). Extensor lag was not associated with immobilization type, improving from a mean preoperative lag of 43° to a mean postoperative lag of 9°. Among successes, University of California at Los Angeles activity and Knee Injury and Osteoarthritis Outcome Score - Joint Replacement score improvements exceeded minimal clinically important difference (2.2-3.3 and 52.5-64.0, respectively).ConclusionMarlex mesh EM reconstruction is a durable and reliable treatment with acceptable clinical results achievable outside the designer institution. Provided sufficient duration and compliance with postoperative immobilization, similar outcomes can be obtained with either a cast immobilizer or a knee immobilizer.