系统中药学指导下的益母草多维评价研究

系统中药学是基于现代中药学学科的开创者凌一揆教授"大中药"的思想,是研究中药复杂系统品种、品质、制药、药性、功效、应用等关键要素发生、发展、变化的科学。本文论述了系统中药学的科学内涵,报告了在系统中药学指导下益母草"品质制性效应"的研究实践。     

朝鲜淫羊藿酸性多糖的理化特性及对HepG2细胞脂质堆积的改善作用＊

目的 对比研究朝鲜淫羊藿酸性多糖酯化还原前后的理化特性，并探讨其改善油酸诱导的肝癌HepG2细胞脂质堆积活性的差异。方法 采用高效凝胶渗透色谱法测定朝鲜淫羊藿酸性多糖（EFPA）的均一性和分子量，高效液相色谱法测定EFPA和酯化还原后朝鲜淫羊藿酸性多糖（EFPA-R）的单糖组成；采用油酸（OA）处理HepG2细胞诱导建立脂质蓄积模型，不同浓度EFPA与EFPA-R（10、30、100、300 μg·mL^-1）分别和OA共同作用于细胞24 h，采用CCK-8试剂盒测定细胞存活率，油红O染色观察细胞内脂滴蓄积情况，并采用试剂盒测定细胞内总胆固醇（TC）、甘油三酯（TG）含量。结果 EFPA为成分均一的多糖组分，分子量为125.8 kDa，由甘露糖、葡萄糖、半乳糖、葡萄糖醛酸和阿拉伯糖组成，摩尔比为1.7∶7.4∶1.4∶1.8∶1.0，葡萄糖占比最大，EFPA-R由甘露糖、葡萄糖、半乳糖和阿拉伯糖组成，摩尔比为0.8∶10.6∶2.1∶1.0；在10-300 μg·mL^-1范围内，EFPA和EFPA-R对HepG2细胞的抑制作用较弱，作为给药浓度；与空白组相比，模型组细胞中TC、TG含量显著升高（P < 0.01），细胞内红色脂滴显著增多，与模型组相比，EFPA可显著降低细胞中TC、TG含量（P < 0.01），明显减少细胞内红色脂滴（P < 0.05或P < 0.01），EFPA-R干预后细胞则无明显变化。结论 EFPA可明显改善HepG2细胞脂质堆积情况，且呈现剂量依赖性，而半乳糖醛酸（GalA）的存在可能是其抑制HepG2细胞脂质蓄积的关键因素。     

基于数据挖掘和“味性化味”理论的藏医治疗疫病用药规律及肺疫方剂药性研究＊

目的 研究藏医治疗疫病的用药规律及肺疫方剂药性。方法 收集和整理藏医古籍文献中治疗疫病的方剂，运用IBM SPSS软件进行藏药频数、聚类和因子分析，运用SPSS Modeler和TBtools软件分别进行关联规则分析和肺疫病方剂的药性聚类分析。结果 共纳入160首方剂，涉及219味藏药材，统计频次≥16的高频藏药材34种，多以清热、解毒祛瘟和消疫药材为主。关联规则分析得到28项药物组，体现出藏医消疫祛邪、调隆祛寒的用药特点。聚类分析得到8个药物组合，反应了泻疫解毒和除瘟镇痛的藏医治法特点。因子分析提出6个公因子，反应了驱虫止疠的藏医治法，并表明藏药五味麝香丸在治疗疫病方剂配伍中占有举足轻重的地位。治疗肺疫经典方剂的藏药材主要以草本类药材为主。方剂药性聚类结果显示凉、钝、稀等治疗赤巴的药性值最高，符合藏医消疫、清热和调“隆”的治疗原则。结论 藏医治疗肺疫病主要采取消疫清热为主、调“隆”补益为辅的治疗原则。     

Structural Response Prediction of Thin-Walled Additively Manufactured Parts Considering Orthotropy,Thickness Dependency and Scatter

Besides the design freedom offered by additive manufacturing, another asset lies within its potential to accelerate product development processes by rapid fabrication of functional prototypes. The premise to fully exploit this benefit for lightweight design is the accurate structural response prediction prior to part production. However, the peculiar material behavior, characterized by anisotropy, thickness dependency and scatter, still constitutes a major challenge. Hence, a modeling approach for finite element analysis that accounts for this inhomogeneous behavior is developed by example of laser-sintered short-fiber-reinforced polyamide 12. Orthotropic and thickness-dependent Young’s moduli and Poisson’s ratios were determined via quasi-static tensile tests. Thereof, material models were generated and implemented in a property mapping routine for finite element models. Additionally, a framework for stochastic finite element analysis was set up for the consideration of scatter in material properties. For validation, thin-walled parts on sub-component level were fabricated and tested in quasi-static three-point bending experiments. Elastic parameters showed considerable anisotropy, thickness dependency and scatter. A comparison of the predicted forces with experimentally evaluated reaction forces disclosed substantially improved accuracy when utilizing the novel inhomogeneous approach instead of conventional homogeneous approaches. Furthermore, the variability observed in the structural response of loaded parts could be reproduced by the stochastic simulations.     

The Cystine Knot Is Responsible for the Exceptional Stability of the Insecticidal Spider Toxin ω-Hexatoxin-Hv1a

The inhibitor cystine knot (ICK) is an unusual three-disulfide architecture in which one of the disulfide bonds bisects a loop formed by the two other disulfide bridges and the intervening sections of the protein backbone. Peptides containing an ICK motif are frequently considered to have high levels of thermal, chemical and enzymatic stability due to cross-bracing provided by the disulfide bonds. Experimental studies supporting this contention are rare, in particular for spider-venom toxins, which represent the largest diversity of ICK peptides. We used ω-hexatoxin-Hv1a (Hv1a), an insecticidal toxin from the deadly Australian funnel-web spider, as a model system to examine the contribution of the cystine knot to the stability of ICK peptides. We show that Hv1a is highly stable when subjected to temperatures up to 75 °C, pH values as low as 1, and various organic solvents. Moreover, Hv1a was highly resistant to digestion by proteinase K and when incubated in insect hemolymph and human plasma. We demonstrate that the ICK motif is essential for the remarkable stability of Hv1a, with the peptide’s stability being dramatically reduced when the disulfide bonds are eliminated. Thus, this study demonstrates that the ICK motif significantly enhances the chemical and thermal stability of spider-venom peptides and provides them with a high level of protease resistance. This study also provides guidance to the conditions under which Hv1a could be stored and deployed as a bioinsecticide.     

Non-invasive evaluation of breast cancer response to chemotherapy using quantitative ultrasonic backscatter parameters

Tumor response to neoadjuvant chemotherapy in patients (n = 30) with locally advanced breast cancer (LABC) was examined using quantitative ultrasound. Three ultrasound backscatter parameters, the integrated backscatter coefficient (IBC), average scatterer diameter (ASD), and average acoustic concentration (AAC), were estimated from tumors prior to treatment and at four times during neoadjuvant chemotherapy treatment (weeks 0, 1, 4, 8, and prior to surgery) and compared to ultimate clinical and pathological tumor responses. Results demonstrated that among all parameters, AAC was the best indicator of tumor response early after starting treatment. The AAC parameter increased substantially in treatment-responding patients as early as one week after treatment initiation, further increased at week 4, and attained a maximum at week 8. In contrast, the backscatter parameters from non-responders did not show any changes after treatment initiation. The two patient populations exhibited a statistically significant difference in changes of AAC (p < 0.001) and ASD (p = 0.023) over all treatment times examined. The best prediction of treatment response was achieved with the combination of AAC and ASD at week 4 (82% sensitivity, 100% specificity, and 86% accuracy) of 12–18 weeks of treatment. The survival of patients with responsive ultrasound parameters was higher than patients with non-responsive ultrasound parameters (35 ± 11 versus 27 ± 11 months, respectively, p = 0.043). This study demonstrates that ultrasound parameters derived from the ultrasound backscattered power spectrum can potentially serve as non-invasive early measures of clinical tumor response to chemotherapy treatments.     

Monolithic crowns fracture analysis: The effect of material properties,cusp angle and crown thickness

ObjectivesThis study aimed to investigate the collective influence of material properties and design parameters on the fracture behavior of monolithic dental crowns.MethodsThree-dimensional (3D) models (N = 90) with different combinations of design parameters (thickness, cusp angle and occlusal notch geometry) and material type (lithium disilicate, feldspar ceramic, zirconia, hybrid resin ceramic and hybrid polymer-infiltrated ceramic) were developed for the failure analysis using extended finite element method (XFEM) to identify the stress distribution, crack initiation load, fracture surface area and fracture pattern. Analytical formulation, in vitro fracture tests and fractographic analysis of dedicated models were also performed to validate the findings of the XFEM simulation.ResultsFor all material types considered, crowns with a sharp occlusal notch design had a significantly lower fracture resistance against occlusal loading. In most of the models, greater crown thickness and cusp angle resulted in a higher crack initiation load. However, the effect of cusp angle was dominant when the angle was in the low range of 50° for which increasing thickness did not enhance the crack initiation load.SignificanceComparing the critical load of crack initiation for different models with the maximum biting force revealed that for the studied monolithic materials excluding zirconia, a design with a rounded occlusal notch, 70° cusp angle and medium thickness (1.5 mm occlusal) is an optimum combination of design parameters in terms of tooth conservation and fracture resistance. Zirconia crowns exhibited sufficient strength for a more conservative design with less thickness (1.05 mm occlusal) and sharper cusp angle (60°).     

Fractal dimension in CT low attenuation areas is predictive of long-term oxygen therapy initiation in COPD patients: Results from two observational cohort studies

BackgroundSome chronic obstructive pulmonary disease (COPD) patients develop hypoxemia with disease progression, with some even requiring long-term oxygen therapy (LTOT). Lung function, especially diffusing capacity, and the annual decline in PaO₂, are reported to be predictive factors of chronic respiratory failure. However, the association between lung morphometry evaluated using computed tomography (CT) images and LTOT initiation is unknown.MethodsWe retrospectively evaluated the relationship between clinical indices, including pulmonary function, body mass index (BMI), and CT parameters, at baseline and LTOT initiation in two prospective COPD cohorts. In the Nara Medical University cohort (n = 76), the low attenuation area (LAA) and its fractal dimension (fractal D) were adapted as the indices for parenchymal destruction in CT images. The association between these CT measurements and LTOT initiation was replicated in the Kyoto University cohort (n = 130).ResultsIn the Nara Medical University cohort, lower BMI (hazard ratio [HR]:0.70, p = 0.006), lower % diffusing capacity (%DLCO) (HR: 0.92, p = 0.006), lower %DLCO/VA (HR, 0.90, p = 0.008), higher RV/TLC (HR, 1.26, p = 0.012), higher LAA% (HR: 1.18, p = 0.001), and lower fractal D (HR: 3.27 × 10^?8, p < 0.001) were associated with LTOT initiation. Multivariate analysis in the Kyoto University cohort confirmed that lower %DLCO and lower fractal D were independently associated with LTOT initiation, whereas LAA% was not.ConclusionFractal D, which is the index for morphometric complexity of LAA in CT analysis, is predictive of LTOT initiation in COPD patients.     

基于物料性质表征技术的蒲地蓝消炎口服液 儿童用药顺应性改善研究

蒲地蓝消炎口服液安全有效,显效迅速,临床应用广泛,但在儿科用药领域,由于用药剂量不明确与口服顺应性差成为制约其发展的主要原因。基于此,本研究通过分析其问题产生的根源并深入探究其解决方案,通过物料性质表征技术、复合矫味技术、剂型优化技术以提升蒲地蓝消炎口服液的口服顺应性,同时探讨蒲地蓝消炎口服液的儿童精准用药策略,为儿童精准用药的临床前研究提供技术指导。