Nanotechnology for colorectal cancer detection and treatment

Colorectal cancer (CRC) is the third most diagnosed cancer and the second leading cause of cancer-related mortality in the United States. Across the globe, people in the age group older than 50 are at a higher risk of CRC. Genetic and environmental risk factors play a significant role in the development of CRC. If detected early, CRC is preventable and treatable. Currently, available screening methods and therapies for CRC treatment reduce the incidence rate among the population, but the micrometastasis of cancer may lead to recurrence. Therefore, the challenge is to develop an alternative therapy to overcome this complication. Nanotechnology plays a vital role in cancer treatment and offers targeted chemotherapies directly and selectively to cancer cells, with enhanced therapeutic efficacy. Additionally, nanotechnology elevates the chances of patient survival in comparison to traditional chemotherapies. The potential of nanoparticles includes that they may be used simultaneously for diagnosis and treatment. These exciting properties of nanoparticles have enticed researchers worldwide to unveil their use in early CRC detection and as effective treatment. This review discusses contemporary methods of CRC screening and therapies for CRC treatment, while the primary focus is on the theranostic approach of nanotechnology in CRC treatment and its prospects. In addition, this review aims to provide knowledge on the advancement of nanotechnology in CRC and as a starting point for researchers to think about new therapeutic approaches using nanotechnology.     

Unconditional Positivity-Preserving and Energy Stable Schemes for a Reduced Poisson-Nernst-Planck System

The Poisson-Nernst-Planck (PNP) system is a widely accepted model for simulation of ionic channels. In this paper, we design, analyze, and numerically validate a second order unconditional positivity-preserving scheme for solving a reduced PNP system, which can well approximate the three dimensional ion channel problem. Positivity of numerical solutions is proven to hold true independent of the size of time steps and the choice of the Poisson solver. The scheme is easy to implement without resorting to any iteration method. Several numerical examples further confirm the positivity-preserving property, and demonstrate the accuracy, efficiency, and robustness of the proposed scheme, as well as the fast approach to steady states.     

预防性静滴钾离子、镁离子对急性心梗后并发室性心律失常的预防作用

目的 探究预防性静滴钾离子、镁离子对急性心梗后并发室性心律失常的预防作用。方法 选择2015年1月-2018年1月于西宁市第一人民医院进行治疗的78例急性心肌梗死患者为研究对象，按照随机数字表法将其均分为观察组与对照组，每组各39例患者。对照组患者进行常规急性心梗治疗，观察组患者在对照组基础上加用门冬氨酸钾镁进行治疗，对比两组治疗有效率，对比两组治疗前后血液流变学指标纤维蛋白原（Fib）、凝血酶原时间（PT）、血小板计数（Plt），对比两组治疗期间不良反应发生率及心律失常发生率。结果 治疗后，观察组患者治疗有效率为87.18%，对照组为76.92%，两组对比差异具有统计学意义（P<0.05）。治疗前两组患者Fib、PT以及Plt水平对比差异不具有统计学意义；治疗后，两组患者Plt及Fib水平低于治疗前，PT水平高于治疗前，差异有统计学意义（P<0.05）；治疗后观察组患者Plt及Fib水平低于对照组，PT水平高于对照组（P<0.05）。观察组患者不良反应发生率稍高于对照组，但对比差异不具有统计学意义。观察组心律失常发生率为7.69%，对照组为15.38%，两组对比差异具有统计学意义（P<0.05）。结论 预防性静滴钾离子与镁离子能够显著降低急性心梗患者心律失常发生率，同时有利于提高治疗有效率，改善其血流变指标，且安全性较高。     

基于UPLC-LTQ-Orbitrap-MS分析刺果番荔枝叶的化学成分

目的利用UPLC-LTQ-Orbitrap-MS技术对刺果番荔枝叶的化学成分进行定性分析。方法采用Waters Acquity UPLC HSS T 3色谱柱(2.1 mm×100 mm,1.8μm),流动相为0.1%甲酸水(A)和乙腈(B)梯度洗脱,流速为0.3 mL/min,进样量2μL,在电喷雾正负离子模式下采集数据。经Reaxys数据库检索番荔枝属类化合物信息,通过质谱信息比对各化合物的m/z值、保留时间、质谱特征碎片等,并结合文献数据对鉴定的化合物进行验证。结果根据各化合物的特征裂解规律,从刺果番荔枝叶中共鉴定出45个化合物,包括16个生物碱类,14个番荔枝内酯类,7个黄酮类和8个其他类化合物,其中以番荔枝内酯类和生物碱类成分居多,与文献报道番荔枝内酯与生物碱类化合物是发挥抗癌的主要活性成分一致。结论利用UPLC-LTQ-Orbitrap-MS技术对刺果番荔枝叶中的化学成分进行了快速、准确的定性分析,为刺果番荔枝叶的提取分离与药效物质基础的研究提供依据。     

Carboxylesterase catalyzed 18O-labeling of carboxylic acid and its potential application in LC-MS/MS based quantification of drug metabolites

LC-MS quantification of drug metabolites is sometimes impeded by the availability of internal standards that often requires customized synthesis and/or extensive purification. Although isotopically labeled internal standards are considered ideal for LC-MS/MS based quantification, de novo synthesis using costly isotope-enriched starting materials makes it impractical for early stage of drug discovery. Therefore, quick access to these isotope-enriched compounds without chemical derivatization and purification will greatly facilitate LC-MS/MS based quantification. Herein, we report a novel ¹⁸O-labeling technique using metabolizing enzyme carboxylesterase (CES) and its potential application in metabolites quantification study. Substrates of CES typically undergo a two-step oxygen exchange with H₂¹⁸O in the presence of the enzyme, generating singly- and doubly-¹⁸O-labeled carboxylic acids; however, unexpected hydrolytic behavior was observed for three of the test compounds – indomethacin, piperacillin and clopidogrel. These unusual observations led to the discovery of several novel hydrolytic mechanisms. Finally, when used as internal standard for LC-MS/MS based quantification, these in situ labeled compounds generated accurate quantitation comparable to the conventional standard curve method. The preliminary results suggest that this method has potential to eliminate laborious chemical synthesis of isotope-labeled internal standards for carboxylic acid-containing compounds, and can be developed to facilitate quantitative analysis in early-stage drug discovery.     

急性一氧化碳中毒后迟发性脑病的临床表现和影像学特点

目的探讨急性一氧化碳中毒后迟发性脑病的临床表现和影像学特点及其诊断价值。方法回顾性对23例急性一氧化碳中毒后迟发性脑病的临床表现和影像学特点进行归纳和分析。结果23例患者中智能障碍23例（100％），言语功能障碍17例（73.9％），另有共济失调精神障碍帕金森综合症及尿失禁等。头部CT和MRI主要表现为皮层下脑白质异常信号及基底节区或苍白球区异常信号，极少累及大脑皮质脑干和小脑。结论急性一氧化碳中毒后迟发性脑病的诊断主要依靠病史和临床症状，MRI比CT更有诊断价值。     

Ex Vivo Application of Carbon Monoxide in University of Wisconsin Solution to Prevent Intestinal Cold Ischemia/Reperfusion Injury

Carbon monoxide (CO), a byproduct of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. In vivo recipient CO inhalation at low concentrations prevented ischemia/reperfusion (I/R) injury associated with small intestinal transplantation (SITx). This study examined whether ex vivo delivery of CO in University of Wisconsin (UW) solution could ameliorate intestinal I/R injury. Orthotopic syngenic SITx was performed in Lewis rats after 6 h cold preservation in control UW or UW that was bubbled with CO gas (0.1-5%) (CO-UW). Recipient survival with intestinal grafts preserved in 5%, but not 0.1%, CO-UW improved to 86.7% (13/15) from 53% (9/17) with control UW. At 3 h after SITx, grafts stored in 5% CO-UW showed improved intestinal barrier function, less mucosal denudation and reduced inflammatory mediator upregulation compared to those in control UW. Preservation in CO-UW associated with reduced vascular resistance (end preservation), increased graft cyclic guanosine monophosphate levels (1 h), and improved graft blood flow (1 h). Protective effects of CO-UW were reversed by ODQ, an inhibitor of soluble guanylyl cyclase. In vitro culture experiment also showed better preservation of vascular endothelial cells with CO-UW. The study suggests that ex vivo CO delivery into UW solution would be a simple and innovative therapeutic strategy to prevent transplant-induced I/R injury.     

Heterodetic bicyclic decapeptide cyclo (Glu1 -Leu2 -Pro3-Gly4-Ser5-Ile6-Pro7-Ala8) cyclo-(1γ-5β) Phe9-Gly10

Bycyclic peptides are useful model molecules that can mimic the constrained local folding of a great number of natural peptides and proteins, such as ionophoric peptides, enzyme active site, and ligand-receptor active site. The synthesis of the bicyclic title compound with the liquid phase method is described with experimental details. Of particular interest is the heterodetic closure of the second ring. The peptide showed a complexing activity with metal cations like Ba²⁺, Ca²⁺, and Mg²⁺ . The free bicyclic peptide conformation in solution has been studied by means of NMR spectroscopy and a plausible structure model worked out with model building on NMR constraints is proposed.