Modeling the effects of particles,interstitials, vacancies and tip geometry on indentation-induced plasticity

In this work, which is a follow-up of an earlier work by the authors in this journal, we discuss the effects of particles, interstitials, vacancies and indenter-tip geometry on indentation-induced plasticity. A nano-indentation model based on a close-packed array of straws was used. Upon indentation with a cylindrical indenter, the results observed in situ, match qualitatively computer atomistic and finite-element simulation models. This model helps explain the phenomenon and physical reasons for annihilation of vacancies. It also shows the strong effect of interstitials on the inception of plasticity at their sites. It shows that a rigid particle acts as a stress concentrator even away from the indenter. On indentation with a flat indenter, curling of atoms at the indenter edges was observed, along with slip lines reported in the literature.     

Vascular Gene Transfer from Metallic Stent Surfaces Using Adenoviral Vectors Tethered through Hydrolysable Cross-linkers

In-stent restenosis presents a major complication of stent-based revascularization procedures widely used to re-establish blood flow through critically narrowed segments of coronary and peripheral arteries. Endovascular stents capable of tunable release of genes with anti-restenotic activity may present an alternative strategy to presently used drug-eluting stents. In order to attain clinical translation, gene-eluting stents must exhibit predictable kinetics of stent-immobilized gene vector release and site-specific transduction of vasculature, while avoiding an excessive inflammatory response typically associated with the polymer coatings used for physical entrapment of the vector. This paper describes a detailed methodology for coatless tethering of adenoviral gene vectors to stents based on a reversible binding of the adenoviral particles to polyallylamine bisphosphonate (PABT)-modified stainless steel surface via hydrolysable cross-linkers (HC). A family of bifunctional (amine- and thiol-reactive) HC with an average t_1/2 of the in-chain ester hydrolysis ranging between 5 and 50 days were used to link the vector with the stent. The vector immobilization procedure is typically carried out within 9 hr and consists of several steps: 1) incubation of the metal samples in an aqueous solution of PABT (4 hr); 2) deprotection of thiol groups installed in PABT with tris(2-carboxyethyl) phosphine (20 min); 3) expansion of thiol reactive capacity of the metal surface by reacting the samples with polyethyleneimine derivatized with pyridyldithio (PDT) groups (2 hr); 4) conversion of PDT groups to thiols with dithiothreitol (10 min); 5) modification of adenoviruses with HC (1 hr); 6) purification of modified adenoviral particles by size-exclusion column chromatography (15 min) and 7) immobilization of thiol-reactive adenoviral particles on the thiolated steel surface (1 hr). This technique has wide potential applicability beyond stents, by facilitating surface engineering of bioprosthetic devices to enhance their biocompatibility through the substrate-mediated gene delivery to the cells interfacing the implanted foreign material.     

A quantitative study on magnesium alloy stent biodegradation

Insufficient scaffolding time in the process of rapid corrosion is the main problem of magnesium alloy stent (MAS). Finite element method had been used to investigate corrosion of MAS. However, related researches mostly described all elements suffered corrosion in view of one-dimensional corrosion. Multi-dimensional corrosions significantly influence mechanical integrity of MAS structures such as edges and corners. In this study, the effects of multi-dimensional corrosion were studied using experiment quantitatively, then a phenomenological corrosion model was developed to consider these effects. We implemented immersion test with magnesium alloy (AZ31B) cubes, which had different numbers of exposed surfaces to analyze differences of dimension. It was indicated that corrosion rates of cubes are almost proportional to their exposed-surface numbers, especially when pitting corrosions are not marked. The cubes also represented the hexahedron elements in simulation. In conclusion, corrosion rate of every element accelerates by increasing corrosion-surface numbers in multi-dimensional corrosion. The damage ratios among elements with the same size are proportional to the ratios of corrosion-surface numbers under uniform corrosion. The finite element simulation using proposed model provided more details of changes of morphology and mechanics in scaffolding time by removing 25.7% of elements of MAS. The proposed corrosion model reflected the effects of multi-dimension on corrosions. It would be used to predict degradation process of MAS quantitatively.     

Telocytes and interstitial cells of Cajal in the biliary system

A novel type of interstitial tissue cells in the biliary tree termed telocytes (TCs), formerly known as interstitial Cajal‐like cells (ICLCs), exhibits very particular features which unequivocally distinguish these cells from interstitial cells of Cajal (ICCs) and other interstitial cell types. Current research substantiates the existence of TCs and ICCs in the biliary system (gallbladder, extrahepatic bile duct, cystic duct, common bile duct and sphincter of Oddi). Here, we review the distribution, morphology and ultrastructure of TCs and ICCs in the biliary tree, with emphasis on their presumptive roles in physiological and pathophysiological processes.     

低位胆道恶性梗阻性黄疸术前胆红素异常的处理策略探讨(附134例报告)

目的:探讨低位胆道恶性梗阻性黄疸患者术前胆红素异常的处理策略,以提高该类患者的临床疗效。方法:回顾性分析西京医院肝胆外科2008年1月1日-2017年12月31日收治的符合研究条件的134例低位胆道恶性梗阻性黄疸(术前总胆红素≥171μmol/L)患者,按胆红素水平分为中、重度黄疸组,分析和比较两组术前黄疸的处理方法、术后肝功能、并发症情况等。结果:两组患者胆道引流后总胆红素水平均明显低于引流前,而肝功能Child-Pugh分级比较差异均无统计学意义(P0.05);两组行术前胆道引流患者与未行胆道引流患者的围手术期情况比较均无统计学差异(P0.05);两组行术前胆道引流患者与未行胆道引流患者的手术并发症的发生情况比较均无统计学差异(P0.05)。结论:对于低位胆道恶性梗阻性黄疸患者,无论中度黄疸还是重度黄疸,原则上术前不必行胆道引流。对于伴有脏器功能不全、急性炎症或其他暂不宜手术的患者,可先行胆道引流处理,限期手术。若行术前胆道引流,采用PTCD方式,更为简单安全有效。     

Differential effects of FXR or TGR5 activation in cholangiocarcinoma progression

Background and aims

Cholangiocarcinoma (CCA) is an aggressive tumor type affecting cholangiocytes. CCAs frequently arise under certain cholestatic liver conditions. Intrahepatic accumulation of bile acids may facilitate cocarcinogenic effects by triggering an inflammatory response and cholangiocyte proliferation. Here, the role of bile acid receptors FXR and TGR5 in CCA progression was evaluated.

Natural products as modulators of the nuclear receptors and metabolic sensors LXR,FXR and RXR

Nuclear receptors (NRs) represent attractive targets for the treatment of metabolic syndrome-related diseases. In addition, natural products are an interesting pool of potential ligands since they have been refined under evolutionary pressure to interact with proteins or other biological targets.This review aims to briefly summarize current basic knowledge regarding the liver X (LXR) and farnesoid X receptors (FXR) that form permissive heterodimers with retinoid X receptors (RXR). Natural product-based ligands for these receptors are summarized and the potential of LXR, FXR and RXR as targets in precision medicine is discussed.     

药物洗脱支架植入术与冠状动脉旁路移植术治疗冠心病多支病变伴糖尿病患者的临床效果分析

目的:比较药物洗脱支架(DES)植入术及冠状动脉旁路移植术(CABG)治疗冠心病多支病变伴糖尿病患者的近期及远期临床疗效。方法:回顾性分析2014年1月~2016年10月在哈尔滨医科大学附属第一医院经冠状动脉造影证实为多支血管病变并伴有糖尿病的患者186例,根据血运重建方式的不同分为DES组及CABG组,随访50.5±14.3个月,观察两组患者住院期间及随访期主要不良心脑血管事件(包括非致死心肌梗死、脑卒中、再次血运重建、全因死亡)的发生情况。结果:在所有入选患者中,DES组有更多双支病变(P0.05),CABG组三支病变较多(P0.05),两组在完全血运重建方面无显著性差异(P0.05)。住院期间,CABG组死亡2例(2.3%),DES组死亡1例(1.0%),死亡率比较无统计学意义(P0.05)。两组均未出现非致死性心肌梗死、脑卒中、再次血运重建。出院后对186例入选患者随访,其中失访11例(DES组5例,CABG组6例)。随访期间CABG组发生非致死性心肌梗死1例(1.3%)、脑卒中6例(7.5%)、全因死亡10例(12.5%),DES组发生非致死性心肌梗死5例(5.3%)、脑卒中3例(3.2%)、全因死亡9例(9.5%),两组间比较差异无统计学意义(P0.05);而CABG组再次血运重建2例(2.5%),DES组15例(15.8%),两组比较差异具有统计学意义(P0.01)。结论:行DES置入术或CABG术治疗冠心病多支病变伴糖尿病患者,住院期间主要心脑血管不良事件发生率、远期非致死性心肌梗死、脑卒中、全因死亡发生情况均无显著性差异,但DES组再次血运重建率明显升高,可能与糖尿病患者较高的再狭窄率有关。     

胆道支架置入联合介入化疗对恶性胆道梗阻患者肝功能及预后的影响

目的:研究胆道支架置入联合介入化疗对恶性胆道梗阻患者肝功能及预后的影响,为临床治疗提供依据。方法:选取2013年2月到2015年2月我院收治的恶性胆道梗阻患者90例,按照随机数字表法将患者分为Ⅰ组、Ⅱ组和Ⅲ组,每组30例,Ⅰ组给予胆道支架置入联合介入化疗,Ⅱ组给予单纯胆道支架置入,Ⅲ组给予保守治疗,比较三组治疗前、后肝功能、并发症、支架通畅率及生存期。结果:治疗前三组谷草转氨酶(AST)、谷丙转氨酶(ALT)、γ-谷氨酰转移酶(r-GT)比较无统计学意义(P0.05),治疗后Ⅰ组和Ⅱ组AST、ALT和r-GT均显著改善,与治疗前和Ⅲ组比较差异具有统计学意义(P0.05),且I组显著优于Ⅱ组,比较差异具有统计学意义(P0.05),Ⅲ组治疗后AST、ALT和r-GT与治疗前比较差异无统计学意义(P0.05);Ⅰ组、Ⅱ组和Ⅲ组并发症发生率比较无统计学意义(P0.05);Ⅰ组术后3个月、6个月和12个月支架通畅率均显著高于Ⅱ组,比较差异具有统计学意义(P0.05);I组生存期显著高于Ⅱ组和Ⅲ组,Ⅱ组高于Ⅲ组,比较差异具有统计学意义(P0.05)。结论:胆道支架置入联合介入化疗治疗恶性胆道梗阻具有较好效果,能明显改善患者肝功,延长患者生存期。