CPV方案术前诱导化疗治疗口腔颌面部鳞癌的临床研究

58例Ⅱ-Ⅳ期口腔颌面部鳞癌患者，用卡铂（400mg／m2，第1天）、平阳霉素（6mg／m2，1～15天）、长春新碱（1．4mg／m2，1，9天）联合化疗总有效率为81．1％，其中51例化疗后施行手术治疗，其3、5年生存率分别为70．6％、67．6％。术前化疗有效者对提高生存率有重要意义，化疗后及时手术治疗是进一步提高疗效的主要途径。     

Proteomic assessment of sulfur mustard-induced protein adducts and other protein modifications in human epidermal keratinocytes

Although some toxicological mechanisms of sulfur mustard (HD) have been uncovered, new knowledge will allow for advanced insight in the pathways that lead towards epidermal-dermal separation in skin. In the present investigation, we aimed to survey events that occur at the protein level in human epidermal keratinocytes (HEK) during 24 h after exposure to HD. By using radiolabeled ¹⁴C-HD, it was found that proteins in cultured HEK are significant targets for alkylation by HD. HD-adducted proteins were visualized by two-dimensional gel electrophoresis and analyzed by mass spectrometry. Several type I and II cytokeratins, actin, stratifin (14-3-3σ) and galectin-7 were identified. These proteins are involved in the maintenance of the cellular cytoskeleton. Their alkylation may cause changes in the cellular architecture and, in direct line with that, be determinative for the onset of vesication. Furthermore, differential proteomic analysis was applied to search for novel features of the cellular response to HD. Partial breakdown of type I cytokeratins K14, K16 and K17 as well as the emergence of new charge variants of the proteins heat shock protein 27 and ribosomal protein P0 were observed. Studies with caspase inhibitors showed that caspase-6 is probably responsible for the breakdown of type I cytokeratins in HEK. The significance of the results is discussed in terms of toxicological relevance and possible clues for therapeutic intervention.     

中医研究应进行系统论指导下的还原分析

比较中西思维模式的不同特点:原子论与元气论、机械分析与"天人合一"、单相概念与意象范畴、逻辑推理与直觉体悟、定量实验与比类取象。认为脱胎于中国传统文化的中医学应该:明确概念、逻辑推理,重视关系本体论,建立体现自身特色的检测指标体系,在系统论指导下还原分析。     

Radiofluorination and reductive amination using a microfluidic device

A commercial microfluidic device (NanoTek, Advion) was used as a synthesis platform for the preparation of fluorine‐18 labelled tertiary amines in two consecutive steps. Firstly, the nucleophilic radiofluorination of an aromatic aldehyde and secondly, the reductive amination to produce the corresponding amine. Fluorine‐18 labelled [¹⁸F]fluorobenzaldehyde ([¹⁸F]2) was obtained in an analytical radiochemical yield (rcy) of 93% and a preparative yield of 60% (decay corrected). The produced [¹⁸F]2 was applied in two model reactions yielding [¹⁸F]5 and [¹⁸F]6 in analytical rcy 70 and 75%, respectively. To further test the utility of this methodology, a delta opioid agonist, [¹⁸F]8, was also radiolabelled using the same setup in an analytical rcy of 29%. In a preparative run, 1050 MBq (28.4 mCi) isolated product ([¹⁸F]6) was obtained in a 37.5% decay corrected overall rcy calculated from [¹⁸F]fluoride. The radiochemical purity of [¹⁸F]6 was greater than 99% and the specific radioactivity 298 GBq/µmol (8052 Ci/mmol) at end of synthesis.     

DNA alkylation lesions and their repair in human cells: modification of the comet assay with 3-methyladenine DNA glycosylase (AlkD)

3-Methyladenine DNA glycosylase (AlkD) belongs to a new family of DNA glycosylases; it initiates repair of cytotoxic and promutagenic alkylated bases (its main substrates being 3-methyladenine and 7-methylguanine). The modification of the comet assay (single cell gel electrophoresis) using AlkD enzyme thus allows assessment of specific DNA alkylation lesions. The resulting baseless sugars are alkali-labile, and under the conditions of the alkaline comet assay they appear as DNA strand breaks. The alkylating agent methyl methanesulfonate (MMS) was used to induce alkylation lesions and to optimize conditions for the modified comet assay method with AlkD on human lymphoblastoid (TK6) cells. We also studied cellular and in vitro DNA repair of alkylated bases in DNA in TK6 cells after treatment with MMS. Results from cellular repair indicate that 50% of DNA alkylation is repaired in the first 60 min. The in vitro repair assay shows that while AlkD recognises most alkylation lesions after 60 min, a cell extract from TK6 cells recognises most of the MMS-induced DNA adducts already in the first 15 min of incubation, with maximum detection of lesions after 60 min’ incubation. Additionally, we tested the in vitro repair capacity of human lymphocyte extracts from 5 individuals and found them to be able to incise DNA alkylations in the same range as AlkD. The modification of the comet assay with AlkD can be useful for in vitro and in vivo genotoxicity studies to detect alkylation damage and repair and also for human biomonitoring and molecular epidemiology studies.     

原位及复位融合腰椎滑脱的三维有限元分析

背景：由于脊柱结构复杂,对复位或原位融合后融合的腰椎节段应力分布变化特点的精确生物力学分析一直是个难点。 目的：通过建立L₄/₅节段退变性滑脱原位椎间融合椎弓根钉内固定和复位椎间融合椎弓根钉内固定的三维有限元模型来比较腰椎滑脱原位融合和复位融合两种手术方式在各种载荷下的生物力学变化及其对腰椎稳定的影响。 方法：根据健康成年男性的下腰椎CT数据,利用mimics,Catia和Patran,Marc等软件建立起L₄/₅节段的三维有限元模型,利用此模型模拟退变性腰椎滑脱,在此基础上建立L₄/₅节段原位椎间融合椎弓根钉内固定和复位椎间融合内固定模型,分析两模型在各种载荷下的应力分布特点,并比较异同。 结果与结论：L₄/₅节段退变性滑脱原位椎间融合椎弓根钉内固定和复位椎间融合椎弓根钉内固定三维有限元模型在前屈后伸侧屈旋转负荷下,该节段各部结构,包括椎体,椎弓根钉内固定器和椎间融合器上的应力变化没有显著差异。两模型都显示椎间融合器和椎弓根螺钉内固定器上分布的应力最大。结果表明退变性腰椎滑脱,行原位椎间融合内固定和复位椎间融合内固定后,复位与否对该节段生物力学没有显著影响。     

The excessive use of antioxidant therapy: A possible cause of male infertility?

Reactive oxygen species and oxidative stress are closely associated with various pathologies such as neurodegenerative diseases, ageing and male infertility. Hence, antioxidants such as vitamin C, vitamin E, N‐acetyl cysteine, L‐carnitine and folic acid are regularly used in various treatment regimens to protect cells from the damage induced by free radicals. However, given their over‐the‐counter availability at unnaturally high concentrations and also the fact that they are commonly added to various food products, patients may run a risk of consuming excessive dosages of these compounds, which may then be toxic. The few studies that have assessed antioxidant overuse and the associated adverse effects found that large doses of dietary antioxidant supplements have varying—if any—therapeutic effects even though free radicals clearly damage cells—a phenomenon that has been termed the “antioxidant paradox.” Furthermore, overuse of antioxidants such as vitamin C, vitamin E, N‐acetyl cysteine may lead to reductive stress, which is reported to be as dangerous to cells as oxidative stress and can be the cause of diseases such as cancer or cardiomyopathy. Therefore, we feel that there is a need for more elaborate research to establish the clear benefits and risks involved in antioxidant therapy for male infertility.     

Hyperbranched Poly[bis(alkylene)pyridinium]s

3,5‐Bis(bromomethyl)pyridine hydrobromide and 3,5‐bis(bromobutyl)pyridine hydrobromide were synthesized from commercially available 3,5‐lutidine. The poly(N‐alkylation) of these monomers readily yielded new hyperbranched polyelectrolytes. The progress of reaction was followed by ¹H NMR. A second‐order kinetic scheme fits the experimental data. Rate constants and activation parameters were determined, showing the higher reactivity of 3,5‐bis(bromomethyl)pyridine hydrobromide. This was explained by the electron‐attractive effect of pyridinium groups on the ? CH₂Br end groups. The structures of the hyperbranched poly[3,5‐bis(alkylene)pyridinium]s were investigated by ¹H and ¹³C NMR spectroscopy and a preliminary study of their properties is reported.

     

REVERSIBLE MODIFICATION OF LYSINE IN β-LACTOGLOBULIN USING CITRACONIC ANHYDRIDE

Acylation of lysine in β-lactoglobulin-B with citraconic anhydride resulted in a loss of free sulfhydryl groups. These were not regenerated under the conditions used to remove the modifying groups from lysine. Gel filtration and polyacryl- amide gel electrophoresis of the citraconylated and decitraconylated β-lactoglobulin showed the presence of high molecular weight components. Modification of sulfhydryl groups with N-ethylmaleimide prior to citraconylation prevented the formation of these high molecular weight components. The heterogeneity of the decitraconylated protein was attributed to a combination of inter-molecular disulfide bonding of subunits caused by structural changes occurring during lysine modification and to alkylation of free sulfhydryl groups via the citraconyl double bond.