胃癌靶向治疗药物临床实验研究进展

以往针对进展期胃癌进行化疗常作为其最佳治疗选择,但传统化疗不良反应大,耐药率高,成为治疗难点。近年来,分子靶向药物具有可选择性杀伤肿瘤细胞、药物不良反应小等优点,成为临床研究热点。以受体酪氨酸激酶为靶点的靶向药物联合化疗药物治疗胃癌的多项临床试验证实联合疗法可带来生存效益,将是胃癌治疗的有效手段。本文就胃癌靶向治疗药物临床实验研究进展进行综述。     

药物干预近视眼发生发展的研究现状

近视是儿童及青少年最为常见的眼部疾病。随着近视和高度近视的患病率逐年增加,高度近视及其并发症所导致的低视力及致盲的人数也逐渐增加。但近视的发生和发病机理目前并不清楚,现有的干预方法有光学和药物等措施。本文旨在总结近年来在临床和动物试验期方面讨论药物干预近视的研究进展。     

Erprobungsmethodik für zyklisch überelastisch beanspruchte Bauteile unter Torsion – Bauschinger‐Kenngrößen für 54SiCr6

Power transmission contains several torsion‐stressed parts. Especially shafts and springs are numerous considered. Helical springs as a special type of springs are mainly stressed by torsion load. During operation the spring's load is basically elastic. In some cases, like overload or machine disaster, the load exceeds the spring's yield stress. For a single event the deformations can be calculated easily by using flow charts. However in other cases the spring will be stressed several times with alternating plastic load. Therefore the calculation will not be as easy as in the single load case. Especially the hardening and softening mechanisms have major influence on material behavior. For high strength steel this material behavior is not fully investigated right now. Present article shows a way how to investigate several important Bauschinger parameters based on plastic torsion load for the high strength steel 54SiCr6. Finally it can be shown that 54SiCr6 is influenced by the Bauschinger effect. On the other hand the needed material characteristic can be investigated by the shown methodology. Based on the identified data, analytical and numerical calculation of alternating plastic torsion load can be done.     

A Bayesian adaptive dose-finding algorithm for balancing individual- and population-level ethics in Phase I clinical trials

Multiple Bayesian adaptive designs have been proposed for Phase I clinical trials since the continual reassessment method (CRM) was proposed by O’Quigley et al. (1990). Focused on dose-finding in cancer studies, the CRM seeks to allocate new patients to an estimated maximum tolerable dose (MTD). Later, Whitehead and Brunier (1995 Whitehead, J. and Brunier, H. (1995). Continual Reassessment Method: Bayesian Decision Procedures for Dose Determining Experiments, Statistics in Medicine 14: 885–893.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) applied Bayesian decision theory to maximize statistical information for the MTD when allocating new patients. The two allocation rules reflect conflicting perspectives. The CRM emphasizes individual-level ethics, whereas the method of Whitehead and Brunier (1995 Whitehead, J. and Brunier, H. (1995). Continual Reassessment Method: Bayesian Decision Procedures for Dose Determining Experiments, Statistics in Medicine 14: 885–893.[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]) emphasizes population-level ethics. In the design of a Phase I clinical trial to investigate hyperthermic intraperitoneal chemotherapy (HIPEC) we sought to compromise the two perspectives. To this end, we propose a novel dose allocation design referred to as the balanced information gain method. We first decompose the loss function used by Whitehead and Brunier and then modify it with a tuning parameter that allows a trialist to differentially weigh individual- and population-level ethics based on their particular clinical setting. Simulation studies show that the proposed design provides a reasonable compromise between the distribution of the estimated MTD and the distribution of the number of observed adverse events per trial when compared to the two existing methods.     

H型预应力混凝土护岸桩现场试验研究

为研究H型预应力混凝土护岸桩在内河航道中的适用性,结合湖嘉申线二期航道改建工程,开展了现场试验,对桩土界面处土压力以及桩体内部应力应变进行监测。监测结果表明：背水侧土体的位移受到老护岸和上部荷载的约束,土体被挤得更密实,水平土压力较大;而临水侧是河流且接近河流中轴线,水平土压力较小,最终水平土压力系数在1.1～1.2左右;桩体内部应力大于该型号H型护岸桩的混凝土有效预压应力,沉桩后各测点压应变减小。基于试验结果,对H型护岸桩土压力的计算方法进行了优化,使其更接近于实测值。     

Advantages and limitations of in vitro and in vivo methods of iron and zinc bioavailability evaluation in the assessment of biofortification program effectiveness

ABSTRACT

Biofortification aims to improve the micronutrient concentration of staple food crops through the best practices of breeding and modern biotechnology. However, increased zinc and iron concentrations in food crops may not always translate into proportional increases in absorbed zinc (Zn) and iron (Fe). Therefore, assessing iron and zinc bioavailability in biofortified crops is imperative to evaluate the efficacy of breeding programs. This review aimed to investigate the advantages and limitations of in vitro and in vivo methods of iron and zinc bioavailability evaluation in the assessment of biofortification program effectiveness. In vitro, animal and isotopic human studies have shown high iron and zinc bioavailability in biofortified staple food crops. Human studies provide direct knowledge regarding the effectiveness of biofortification, however, human studies are time consuming and are more expensive than in vitro and animal studies. Moreover, in vitro studies may be a useful preliminary screening method to identify promising plant cultivars, however, these studies cannot provide data that are directly applicable to humans. None of these methods provides complete information regarding mineral bioavailability, thus, a combination of these methods should be the most appropriate strategy to investigate the effectiveness of zinc and iron biofortification programs.     

The Result of Vitamin C Treatment of Patients with Cancer: Conditions Influencing the Effectiveness

Vitamin C (ascorbic acid, AA) is a weak sugar acid structurally related to glucose. All known physiological and biochemical functions of AA are due to its action as an electron donor. Ascorbate readily undergoes pH-dependent autoxidation creating hydrogen peroxide (H₂O₂). In vitro evidence suggests that vitamin C functions at low concentrations as an antioxidant while high concentration is pro-oxidant. Thus, both characters of AA might be translated into clinical benefits. In vitro obtained results and murine experiments consequently prove the cytotoxic effect of AA on cancer cells, but current clinical evidence for high-dose intravenous (i.v.) vitamin C’s therapeutic effect is ambiguous. The difference might be caused by the missing knowledge of AA’s actions. In the literature, there are many publications regarding vitamin C and cancer. Review papers of systematic analysis of human interventional and observational studies assessing i.v. AA for cancer patients’ use helps the overview of the extensive literature. Based on the results of four review articles and the Cancer Information Summary of the National Cancer Institute’s results, we analyzed 20 publications related to high-dose intravenous vitamin C therapy (HAAT). The analyzed results indicate that HAAT might be a useful cancer-treating tool in certain circumstances. The AA’s cytotoxic effect is hypoxia-induced factor dependent. It impacts only the anoxic cells, using the Warburg metabolism. It prevents tumor growth. Accordingly, discontinuation of treatment leads to repeated expansion of the tumor. We believe that the clinical use of HAAT in cancer treatment should be reassessed. The accumulation of more study results on HAAT is desperately needed.     

Influence of Flavor on Goat Feeding Preferences

Goat feeding preferences for straw pellets flavored with ryegrass (Lolium perenne, cv. Belida) or white clover (Trifolium repens, cv. Huia) aromatic extracts, obtained by means of a cold aromatic extraction method, were assessed with cafeteria trials. Prior to the trials, odor differences between the two plant species, the two aromatic extracts, and the straw pellets sprayed with the two aromatic extracts were verified using sensory analysis performed by 30 human panelists. Since odor differences observed among fresh samples were still detectable in aromatic extracts and moistened pellets, the extraction method was considered effective in reproducing plant odors. Straw pellets sprayed with either distilled water (W) or ryegrass (R) or clover (C) aromatic extracts were used to assess flavor preferences of 12 female Rossa Mediterranea goats. Sprayed pellet preference was evaluated in two sessions conducted in two consecutive weeks. Each session consisted of three two-choice presentations performed on three consecutive days. In both sessions, food intake, proportion of food intake, time spent feeding, and proportion of time spent feeding were significantly affected by pellet type (0.05 > P > 0.001). In particular, straw pellets sprayed with ryegrass extract were highly selected compared to those sprayed with clover (0.01 > P > 0.001) or water (0.01 > P > 0.001). In addition, in the second session, the clover extract was preferred to distilled water (0.05 > P > 0.01). The results of this study gave two main indications: first, goat selectivity for ryegrass against clover was consistent even when straw pellets sprayed with odors of these plants were offered, and secondly, the addition of aromatic extracts to straw pellets increased the preference for pellets.     

韦5断块稠油油藏常温改性水驱实践与认识

苏北盆地高邮凹陷韦5块稠油油藏是近年发现的普通Ⅰ、Ⅱ级稠油油藏，具有砂泥岩薄互层中、低渗特征。自投入开发以来，韦5断块先后开展了蒸汽吞吐、酸化储层改造、微生物吞吐、高导短缝水力压裂、注常温改性水驱等多种矿场试验，取得了一定的成果与认识。本文重点介绍注常温改性水驱矿场试验情况，这将对该区块油藏下步开发工作及同类型油藏的开发具有积极的指导意义。