The pig as a model system for investigating the recruitment and contribution of myofibroblasts in skin healing

In the skin-healing field, porcine models are regarded as a useful analogue for human skin due to their numerous anatomical and physiological similarities. Despite the widespread use of porcine models in skin healing studies, the initial origin, recruitment and transition of fibroblasts to matrix-secreting contractile myofibroblasts are not well defined for this model. In this review, we discuss the merit of the pig as an animal for studying myofibroblast origin, as well as the challenges associated with assessing their contributions to skin healing. Although a variety of wound types (incisional, partial thickness, full thickness, burns) have been investigated in pigs in attempts to mimic diverse injuries in humans, direct comparison of human healing profiles with regards to myofibroblasts shows evident differences. Following injury in porcine models, which often employ juvenile animals, myofibroblasts are described in the developing granulation tissue at 4 days, peaking at Days 7–14, and persisting at 60 days post-wounding, although variations are evident depending on the specific pig breed. In human wounds, the presence of myofibroblasts is variable and does not correlate with the age of the wound or clinical contraction. Our comparison of porcine myofibroblast-mediated healing processes with those in humans suggests that further validation of the pig model is essential. Moreover, we identify several limitations evident in experimental design that need to be better controlled, and standardisation of methodologies would be beneficial for the comparison and interpretation of results. In particular, we discuss anatomical location of the wounds, their size and depth, as well as the healing microenvironment (wet vs. moist vs. dry) in pigs and how this could influence myofibroblast recruitment. In summary, although a widespread model used in the skin healing field, further research is required to validate pigs as a useful analogue for human healing with regards to myofibroblasts.     

基于LF-NMR/MRI的维C银翘片制粒中润湿剂评价方法研究

目的应用低场核磁共振时域技术(low field nuclear magnetic resonance time domain technique,LF-NMR)、低场核磁成像技术(low field nuclear magnetic resonance imaging,LF-MRI)对高剪切制粒中润湿剂(乙醇)进行定性、定量分析。方法以维C银翘片高剪切湿法制粒为研究对象,采用LF-NMR建立润湿剂用量测定方法,结合横向弛豫时间(T2)和LFMRI测得的二位影像图对润湿剂分布与变化进行定性分析,探讨峰面积(A₂)与颗粒得率的关系。结果润湿剂用量与A₂呈现良好的相关性(R²=0.9575)。随着润湿剂用量增加,T2向右移动,A₂逐渐增加,质子在增加;LF-MRI表明随着润湿剂用量增加,影像图逐渐清晰,即非结合态质子(束缚态质子及自由态质子)在颗粒中逐渐增加。当润湿剂用量增加至20%~25%时,结合态质子含量不再增加,此时颗粒得率最高。结论LF-NMR和LF-MRI能快速、准确检测制粒中润湿剂用量变化和分布状态,为阐明润湿剂对颗粒性质的影响和成型机制提供评价方法。     

An Investigation on Spray-Granulated,Macroporous, Bioactive Glass Microspheres for a Controlled Drug Delivery System

Bioactive glass (BG) has been regarded as an excellent candidate for biomedical applications due to its superior properties of bioactivity, biocompatibility, osteoconductivity and biodegradability. Thus, in this study, we aimed to fabricate drug carriers that were capable of loading therapeutic antibiotics while promoting bone regeneration using macroporous BG microspheres, prepared by a spray drying method. Characterizations of particle morphology and specific surface area were carried out via scanning electron microscopy and nitrogen adsorption/desorption isotherm. Evaluations of in vitro bioactivity were performed based on Kokubo’s simulated body fluid to confirm the formation of the hydroxyapatite (HA) layer after immersion. In addition, the in vitro drug release behaviors were examined, using tetracycline as the therapeutic antibiotic in pH 7.4 and 5.0 environments. Finally, the results showed that BG microspheres of up to 33 μm could be mass-produced, targeting various therapeutic situations and their resulting bioactivities and drug release behaviors, and related properties were discussed.     

基于AHP-CRITIC混合加权法和Box-Behnken设计-响应面法优化羌芩颗粒成型工艺及其物理指纹图谱研究

目的 优化羌芩颗粒的干法制粒成型工艺,并对颗粒进行质量控制。方法 以颗粒成型率、吸湿率（H）、溶化率和休止角（α）的综合评分为指标,采用Box-Behnken设计-响应面法结合AHP-CRITIC混合加权法建立干法制粒关键工艺参数（critical process parameters,CPPs）和关键质量属性（critical quality attributes,CQAs）的数学模型,通过该模型构建干法制粒的设计空间,并进行蒙特卡洛验证。采用单形格子设计对满足制粒工艺的甘露醇、麦芽糊精、糊精进行辅料配比筛选,确定最佳辅料配比并进行验证。采用粉体学评价方法对羌芩颗粒各项物理质量属性指标进行综合表征,建立由松装密度（D_a）、振实密度（D_c）、α、豪斯纳比（IH）、H、含水量（HR）、颗粒间孔隙率（I_e）、卡尔指数（IC）、比表面积（SSA）、粒径＜50 µm百分比（Pf）、分布宽度（span）、分布范围（width）、均匀性（HG）共13个二级物理质量指标构成的颗粒物理指纹图谱,评价不同批次间颗粒质量的一致性。结果 羌芩颗粒干法制粒CPPs的设计空间为送料频率37～45 Hz,滚轮频率8.0～11.8 Hz,滚轮压力40～50 kg/cm²。最佳辅料配比为甘露醇86%,糊精14%。15批样品物理指纹图谱的相似度均大于0.95。结论 优选后的羌芩颗粒干法制粒成型工艺稳定可行,中间体物理性质质量评价科学合理,可为中药新药的开发及工业化放大生产提供参考。     

活血生肌综合疗法治疗面部肿瘤术后皮肤瘢痕(附34例报告)

目的 探讨活血生肌综合疗法对在面部肿瘤术后皮肤瘢痕的作用机理及临床疗效。方法 以34例面部肿瘤术后切口为抗瘢痕研究对象，分为A组、B组、C组。三组除常规用药外，B组与C组分别给予单纯半导体激光照射及活血生肌综合疗法(生肌活血油 半导体激光照射)治疗。结果 C组在切口周围肿胀程度、疼痛缓解时间、愈合时间、切口愈合瘢痕宽度、患者满意程度等方面明显优于A、B组。结论 活血生肌疗法具有消肿胀、生新肌、通血脉、抗瘢痕的作用，为皮肤瘢痕治疗开辟了一条新的道路，值得临床推广使用。     

不同药用辅料流化床制粒的物性质量分析研究

目的研究5种药用辅料制粒后颗粒的物性指标,分析探讨颗粒物性指标的相关性及颗粒物性质量。方法采用Pearson相关性分析法分析颗粒的7项评价指标相关性,采用主成分分析法对颗粒物性指标进行主成分分析和综合评价。结果粒径分布宽度与松密度及振实密度呈极显著正相关,松密度与振实密度呈极显著正相关,振实密度与压缩度呈显著正相关。对第一主成分产生正向影响较大的物性指标是粒径分布宽度和振实密度。乳糖+水制成的颗粒及甘露醇+水制成的颗粒综合评价得分较高,可溶性淀粉+HPMC制成的颗粒综合评价得分最低。结论不同药用辅料制成的颗粒物性质量存在差异,乳糖和甘露醇分别以水为粘合剂制成的颗粒物性质量较好,可溶性淀粉以HPMC为粘合剂制成的颗粒物性质量较差。     

温肾健脾方对大鼠慢性创面愈合的影响

目的:探讨温肾健脾中药对慢性创面愈合的影响及可能作用机制.方法:采用大鼠背部开放性创面模型,用肌注氢化可的松的方法造成慢性难愈性创面,以辛葡康为阳性对照药,应用免疫组化、流式细胞术等方法,观察创面愈合时间、新生上皮宽度、肉芽组织形态学变化、肉芽组织细胞周期、表皮生长因子(epidermal growth factor, EGF)、转化生长因子β1 (transforming growth factor-β1, TGF-β1)及纤维连接蛋白(fibronectin, FN)等指标.结果:温肾健脾方治疗组与辛葡康对照组平均创面愈合时间分别为(17.0±1.9)和(18.8±1.9) d,较模型组及空白组明显缩短(P<0.05);治疗14 d后,治疗组及对照组新生上皮宽度分别为(3.73±0.19)和(3.21±0.15)mm,较模型组及空白组明显增宽(P<0.05);治疗组新生毛细血管丰富,成纤维细胞数量多,而对照组、模型组及空白组新生毛细血管及成纤维细胞数量均较治疗组明显减少(P <0.05);治疗组S期细胞比例较对照组、模型组及空白组明显提高(P<0.05);治疗组及对照组与模型组及空白组比较,EGF、TGF-β1、FN蛋白表达均增强(P<0.05).结论:温肾健脾方有促进大鼠慢性难愈创面修复的作用,其机制与调节细胞周期,上调EGF、TGF-β1细胞因子蛋白表达水平,促进间质FN的表达有关.     

好氧颗粒污泥的形成及其性质

综述了好氧颗粒污泥的研究进展 ,包括好氧颗粒污泥的基本特征和微生物相、好氧颗粒污泥形成的主要条件及其颗粒化过程、好氧颗粒污泥反应器等 .好氧颗粒污泥是近几年发现的在好氧条件下自发形成的细胞自身固定化颗粒 ,具有良好的沉淀性能、较高的生物量和在高容积负荷条件下降解高浓度有机废水的良好生物活性 .颗粒化过程是一个多阶段的过程 ,取决于废水组成、操作条件和适当的选择压等因素 .SBR反应器 (SequencingBatchReactor)有利于好氧颗粒污泥的形成