Discussion of “Virtual age,is it real?”

In this note, some point of views on virtual ages are presented in terms of the discussion paper written by Finkelstein and Cha, which include generalized stochastic order‐based virtual ages, system‐level virtual ages, virtual ages in Weibull distribution and repair degrees with virtual ages. Finally, some possible future researches on virtual ages are described.     

Self‐assembled Lipid Nanoparticles for Ratiometric Codelivery of Cisplatin and siRNA Targeting XPF to Combat Drug Resistance in Lung Cancer

DNA damage repair through the nucleotide excision repair (NER) pathway is one of the major reasons for the decreased antitumor efficacy of platinum‐based anticancer drugs that have been widely applied in the clinic. Inhibiting the intrinsic NER function may enhance the antitumor activity of cisplatin and conquer cisplatin resistance. Herein, we report the design, optimization, and application of a self‐assembled lipid nanoparticle (LNP) system to simultaneously deliver a cisplatin prodrug together with siRNA targeting endonuclease xeroderma pigmentosum group F (XPF), a crucial component in the NER pathway. The LNP is able to efficiently encapsulate both the platinum prodrug and siRNA molecules with a tuned ratio. Both platinum prodrug and XPF‐targeted siRNA are efficiently carried into cells and released; the former damages DNA and the latter specifically downregulates both mRNA and protein levels of XPF to potentiate the platinum drug, leading to enhanced expression levels of apoptosis markers and improved cytotoxicity in both cisplatin‐sensitive and ‐resistant human lung cancer cells. Our results demonstrate an effective approach to utilize a multi‐targeted nanoparticle system that can specifically silence an NER‐related gene to promote apoptosis induced by cisplatin, especially in cisplatin‐refractory tumors.     

On a single discrete scale for preventive maintenance with two shock processes affecting a complex system

A new approach to optimal maintenance of systems (networks) is suggested. It is applied to systems subject to two external independent shock processes. A system ‘consists’ of two parts, and each shock process affects only its own part. A new notion of bivariate signature is suggested and used for obtaining survival characteristics of a system and further optimization of the preventive maintenance actions. The preventive maintenance optimization is considered in the univariate discrete scale that counts the overall numbers of shocks of both types. An example of a transportation network is considered. Copyright © 2016 John Wiley & Sons, Ltd.     

Multifunctional Fluorinated Lubricant-Infused Poly(4-Hydroxybutyrate) (P4HB) Membranes for Full-Thickness Abdominal Wall Defect Repair

Abdominal wall defect caused by surgical trauma, congenital rupture, or tumor resection may result in hernia formation or even death. Tension-free abdominal wall defect repair by using patches is the gold standard to solve such problems. However, adhesions following patch implantation remain one of the most challenging issues in surgical practice. The development of new kinds of barriers is key to addressing peritoneal adhesions and repairing abdominal wall defects. It is already well recognized that ideal barrier materials need to have good resistance to nonspecific protein adsorption, cell adhesion, and bacterial colonization for preventing the initial development of adhesion. Herein, electrospun poly(4-hydroxybutyrate) (P4HB) membranes infused with perfluorocarbon oil are used as physical barriers. The oil-infused P4HB membranes can greatly prevent protein attachment and reduce blood cell adhesion in vitro. It is further shown that the perfluorocarbon oil-infused P4HB membranes can reduce bacterial colonization. The in vivo study reveals that perfluoro(decahydronaphthalene)-infused P4HB membranes can significantly prevent peritoneal adhesions in the classic abdominal wall defects’ model and accelerate defect repair, as evidenced by gross examination and histological evaluation. This work provides a safe fluorinated lubricant-impregnated P4HB physical barrier to inhibit the formation of postoperative peritoneal adhesions and efficiently repair soft-tissue defects.     

Discovery of Novel Sultone Fused Berberine Derivatives as Promising Tdp1 Inhibitors

A new type of berberine derivatives was obtained by the reaction of berberrubine with aliphatic sulfonyl chlorides. The new polycyclic compounds have a sultone ring condensed to C and D rings of a protoberberine core. The reaction conditions were developed to facilitate the formation of sultones with high yields without by-product formation. Thus, it was shown that the order of addition of reagents affects the composition of the reaction products: when sulfochlorides are added to berberrubine, their corresponding 9-O-sulfonates are predominantly formed; when berberrubine is added to pre-generated sulfenes, sultones are the only products. The reaction was shown to proceed stereo-selectively and the cycle configuration was confirmed by 2D NMR spectroscopy. The inhibitory activity of the synthesized sultones and their 12-brominated analogs against the DNA-repair enzyme tyrosyl-DNA phosphodiesterase 1 (Tdp1), an important target for a potential antitumor therapy, was studied. All derivatives were active in the micromolar and submicromolar range, in contrast to the acyclic analogs and 9-O-sulfonates, which were inactive. The significance of the sultone cycle and bromine substituent in binding with the enzyme was confirmed using molecular modeling. The active inhibitors are mostly non-toxic to the HeLa cancer cell line, and several ligands show synergy with topotecan, a topoisomerase 1 poison in clinical use. Thus, novel berberine derivatives can be considered as candidates for adjuvant therapy against cancer.     

Novel Tdp1 Inhibitors Based on Adamantane Connected with Monoterpene Moieties via Heterocyclic Fragments

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a promising target for anticancer therapy due to its ability to counter the effects topoisomerase 1 (Top1) poison, such as topotecan, thus, decreasing their efficacy. Compounds containing adamantane and monoterpenoid residues connected via 1,2,4-triazole or 1,3,4-thiadiazole linkers were synthesized and tested against Tdp1. All the derivatives exhibited inhibition at low micromolar or nanomolar concentrations with the most potent inhibitors having IC₅₀ values in the 0.35–0.57 µM range. The cytotoxicity was determined in the HeLa, HCT-116 and SW837 cancer cell lines; moderate CC₅₀ (µM) values were seen from the mid-teens to no effect at 100 µM. Furthermore, citral derivative 20c, α-pinene-derived compounds 20f, 20g and 25c, and the citronellic acid derivative 25b were found to have a sensitizing effect in conjunction with topotecan in the HeLa cervical cancer and colon adenocarcinoma HCT-116 cell lines. The ligands are predicted to bind in the catalytic pocket of Tdp1 and have favorable physicochemical properties for further development as a potential adjunct therapy with Top1 poisons.     

Prevention of postoperative tendon adhesion by biodegradable electrospun membrane of poly(lactide-co-glycolide)

An electrospun poly(lactide-co-glycolide)(PLGA) membrane was prepared and used to perform the anti-adhesion of Achilles tendon. Throughout the experiments, the membrane showed an appropriate degradation rate, and the p H values of degradation media were maintained at around 7.4. Simultaneously, the excellent biocompatibility of the membrane in vitro and in vivo was confirmed by live/dead and histopathological analyses. Meanwhile, the membrane can reduce tendon adhesion significantly and promote functional recovery effectively. The encouraging results were further demonstrated by hematoxylin and eosin(HE), and Masson's trichrome stainings, and type I collagen immunohistochemical analysis. It was concluded that the model treated with the electrospun PLGA membrane was significantly better with respect to the adhesion prevention and tissue repair than that without treatment. Considering the results of degradation and adhesion prevention efficacy, the electrospun PLGA membrane would be a great candidate for the prevention of postoperative tendon adhesion.     

PPH加Block术与单纯Block术治疗直肠前突的临床比较研究

目的 探讨吻合器痔上黏膜环切术（PPH 术）加直肠闭式修补术（Block 术）治疗直肠前突的临床疗效。方法 近9年来对女性直肠前突患者先后采用Block 术（36 例）和PPH+Block 术（41 例）治疗,分析两组患者的临床资料,观察并比较其术后第1 天出血量、术后并发症的发生率及疗效。结果 两组患者术后第1 天出血量及术后并发症发生率的差异均无统计学意义（均P＞0.05）。术后3、6、12个月PPH+Block 术组与Block 术组的痊愈率分别为85.4%、82.9%、82.9%和58.3%、52.8%、52.8%,差异均有统计学意义（均P＜0.05）。结论 PPH+Block 术治疗直肠前突较单纯Block 术疗效更好,值得推广应用。     

含多源损伤的胶接修补结构有限元分析方法

采用有限元法研究含多源损伤结构的胶接修补问题,利用二维三层有限元模型对损伤区进行了数值模拟,并选取典型多源损伤情况中含共线双裂纹铝板结构为算例,详细分析了含多裂纹胶接修补结构中两裂纹相对位置、补片尺寸、铺层和厚度对应力强度因子的影响.结果表明,复合材料胶接修补可明显降低含共线双裂纹母板的应力强度因子;对于确定的裂纹和应力场,应对复合材料补片长度和厚度等参数进行优化设计,以获得最佳的修补效果.     

考虑更新延长两阶段保修的二手产品维修策略优化

针对二手产品的维修问题,给出了二手产品生命周期的定义,提出了考虑更新延长两阶段保修的维修策略模型。该策略综合考虑了产品的年龄变化、延保折扣、小修和生产损失费用等因素,从顾客的角度出发,建立以顾客期望总费用率最小化为目标的免费更换保修和按比例更换保修两种策略模型,并给出模型最优化的相关理论证明。算例研究验证了模型的有效性,并对参数的灵敏度进行了分析,文中结论可为顾客进行产品维修计划提供决策依据。