放射性粒子植入治疗不能手术的早期非小细胞肺癌疗效分析

目的:探讨CT引导下经皮穿刺植入125Ⅰ放射性粒子近距离治疗不能外科手术的早期非小细胞肺癌(non-small celllung cancer,NSCLC)的临床疗效。方法:选取2003年1月至2012年12月在天津医科大学第二医院接受治疗的经病理学明确诊断的早期NSCLC患者48例,其中Ⅰ期患者18例,Ⅱ期(N0)患者30例,对患者行CT引导下放射性125Ⅰ粒子植入治疗,术后6个月复查胸部CT,与粒子植入前进行比较,按照国际标准判定疗效。随访截至2013年12月。结果:全部患者顺利完成粒子植入治疗,靶区瘤体MPD(127.3±15.6)Gy,D100(113.1±17.2)Gy,D90(148.6±19.4)Gy,D90>MPD。术后6个月查胸部CT判定疗效,Ⅰ期患者中CR27.8%(5/18),PR 72.2%(13/18),SD、PD为0;Ⅱ期患者中CR 10%(3/30例),PR 73.3%(22/30例),SD 13.3%(4/30),PD 3.3%(1/30)。有效率(CR+PR)为Ⅰ期100%,Ⅱ期83.3%,总有效率89.6%。随访期内全部患者1年局控率85%,1年生存率95.8%(46/48),2年生存率81.3%(39/48),5年生存率56.3%(27/48)。结论:对于不能外科手术的早期非小细胞肺癌,进行CT引导下125Ⅰ放射性粒子植入治疗,是一种微创有效的治疗方法。

单细胞单粒子微束的发展及放射生物学应用现状

综述了单细胞单粒子微束的发展及其在放射生物学方面的应用现状。通过准直或聚焦方式,可以将加速器粒子束流在空气中的束斑限定到微米或亚微米大小,而聚焦微束因其更高的空间分辨率和更快的电磁扫描照射速度成为发展主流;借助于先进的荧光显微镜及微速成像技术,当前的粒子微束能够对活细胞辐射诱导DNA损伤的早期响应进行在线可视化观测。微束对单个细胞或亚细胞结构进行精准定量和定位照射的特点,使其成为低剂量效应、辐射诱导旁效应以及亚细胞结构辐射敏感性研究的重要实验工具,正逐步将其应用从细胞培养模型拓展到更为复杂的组织或体内模型,用于研究受照生物样品辐射响应的空间和时间演化规律。

等离子体鞘层加速模拟质子辐照连续谱数值仿真研究

质子辐照是导致空间飞行器热控涂层性能衰退的重要原因。目前地面多采用单一能量的粒子替代空间能量连续分布的粒子来开展质子辐照模拟试验。文章提出了在一个脉冲宽度内获得连续能量质子谱的方法,即脉冲偏压等离子体鞘层加速方法。文章利用细胞粒子(particle-in-cell,PIC)模型对在3种脉冲偏压三角波作用下等离子体鞘层加速质子以获得连续能量质子谱的动力学过程进行了数值仿真研究,分析了3种脉冲三角波形对鞘层扩展、离子加速及能量分布的影响。结果表明,电势空间分布和离子运动状态紧密联系,鞘层内离子密度变化受到脉冲波形和离子热扩散运动的综合影响,通过调整脉冲偏压三角波形,能够获得不同的能量-剂量分布,从而为下一步工作打下基础。

Phylogeny of Apaturinae Butterflies (Lepidoptera: Nymphalidae) Based on Mitochondrial Cytochrome OxidaseⅠ Gene

The phylogenetic relationships of genera in the subfamily Apaturinae were examined using mtDNA sequence data from 1,471 bp of cytochrome oxidase subunit Ⅰ （COI）. The mitochondrial COI gene from a total of 16 species in 11 genera were sequenced to obtain mtDNA data, along with those of 4 species obtained from GenBank, to construct the MP and the NJ trees using Athyma jina, Penthema adelma, Polyura nepenthes, and Charaxes bernardus as outgroups. The transitions at the third codon positions of the COI data set were found saturated, but they were retained for analysis, because they contain the majority of the phylogenetic information. The impacts of equal weight assumptions for all characters in the parsimonious analysis were assessed by potential alternations in clades in response to different transition/transversion weighting schemes. The results indicated four distinct major groups in Apaturinae. Moreover, several well supported and stable clades were found in the Apaturinae. The study also identified undetermined taxon groups whose positions were weakly supported and were subject to changes under different weighting schemes. Within the Apaturinae, the clustering results are approximately identical to the classical morphological classification. The mtDNA data suggest the genus Mimathyma as a monophyletic group. Lelecella limenitoides and Dilipa fenestra have close relationship with very strong support in all phylogenetic trees. It also supports the taxonomic revision of removing several species from Apatura to other genera, namely Mimathyma schrenckii, M. chevana, M. nycteis, Chitoria subcaerulea, C. fasciola, C. pallas, and Helcyra subalba.

碳量子点作为生物相容性发光材料在再生医学方面的应用

碳纳米材料(CNMs)因在电子、光学、热和机械特性、多用途功能化化学上的作用而受到科学界的关注。由于碳纳米材料的固有疏水性,它们比金属基纳米材料更具有生物相容性和安全性。碳纳米材料(CNMs)可以通过疏水相互作用或π-π堆积来搭载相应的药物,用作高效的药物传递平台。近年来石墨烯、富勒烯、碳纳米管,碳量子点成为治疗癌症以及细胞内标记最广泛使用的碳纳米材料,并且可以通过共价或非共价修饰使这些碳纳米材料具有生物相容性。共价修饰是在其表面引入羟基、羧基或氨基,这些自由基与保护生物聚合物聚乙二醇(PEG)进一步结合,而非共价修饰是在CNMs上负载亲氨性分子。这些碳基纳米材料经过大量的研究证明不仅是各种生物大分子的良好负载载体,而且是很好的光敏剂。此外,许多理想的功能化基团可以被整合到CNMs上,用于肿瘤的主动靶向和归巢。由于CNMs固有的光学特性,许多研究者也对其在肿瘤细胞和干细胞成像的应用上进行了研究,并证明它们是未来生物成像中可靠的材料。在众多的碳基纳米材料中,碳量子点由于特殊的零维结构以及优异的性能不仅在材料领域引起人们的重视,在生物应用方面也备受关注。过去十年来,将基因、生长因子等生物大分子输送到干细胞方法的发展引发了人们对通过纳米药物疗法改善人类疾病治疗的可能性的探索。然而,尽管取得了很大的进展,但在这种基于纳米药物疗法能够在临床环境中安全有效地应用之前,还需要解决很多关键性的技术问题。如干细胞在移植到缺血区域后,由于其微环境的改变,导致干细胞的存活、迁移等状态发生改变。本文综述了这些纳米药物治疗的进展,重点介绍了先进的碳量子点纳米粒子技术,以监控治疗性移植后干细胞在体内和体外的位置,对活细胞体内大分子的示踪以及操控发挥其功能。

Heterogeneity and plasticity of T helper cells

CD4 T helper （Th） cells play critical roles in adaptive immune responses. They recruit and activate other immune cells including B cells, CD8 T cells, macrophages, mast cells, neutrophils, eosinophils and basophils. Based on their functions, their pattern of cytokine secretion and their expression of specific transcription factors, Th cells, differentiated from naive CD4 T cells, are classified into four major lineages, Thl, Th2, Th17 and T regulatory （Treg） cells, although other Th lineages may exist. Subsets of the same lineage may express different effector cytokines, reside at different locations or give rise to cells with different fates, whereas cells from different lineages may secrete common cytokines, such as IL-2, IL-9 and IL-10, resulting in massive heterogeneity of the Th cell population. In addition, the pattern of cytokine secretion may switch from that of one lineage toward another under certain circumstances, suggesting that Th cells are plastic. Tregs are also more heterogeneous and plastic than were originally thought. In this review, we summarize recent reports on heterogeneity and plasticity of Th cells, and discuss potential mechanisms and implications of such features that Th cells display.

Effects of Berbamine on PAF Production in Human Neutrophils and on Platelet Aggregation

The effects of berbamine, an alkaloid of dibenzylisoquinoline, on PAF produc tion in human neutrophils and on platelet aggregation induced by PAF were studied and compared with those of the calcium antagonist verapamil. Preincubation with berbamine (50 mmol / L, 100 mmol / L) or verapamil (10 mmol / L, 100 mmol / L) was shown to significantly inhibit A 23187 stimulated PAF synthesis. Berbamine and verapamil were found to inhibit platelet aggregation induced by PAF 70 pmol / L in a dose dependent manner. These results suggest that the inhibitory effects of berbamine and verapamil on A 23187 stimulated PAF synthesis in human neutrophils and PAF induced platelet aggregation are possibly brought about by inhibiting cellular calcium influx.

Granulocyte-macrophage colony-stimulating factor （GM-CSF） and T-cell responses： what we do and don＇t know

Granulocyte-macrophage colony-stimulating factor （GM-CSF） is an important hematopoietic growth factor and immune modulator. GM-CSF also has profound effects on the functional activities of various circulating leukocytes. It is produced by a variety of cell types including T cells, macrophages, endothelial cells and fibroblasts upon receiving immune stimuli. Although GM-CSF is produced locally, it can act in a paracrine fashion to recruit circulating neutrophils, monocytes and lymphocytes to enhance their functions in host defense. Recent intensive investigations are centered on the application of GM-CSF as an immune adjuvant for its ability to increase dendritic cell （DC） maturation and function as well as macrophage activity. It is used clinically to treat neutropenia in cancer patients undergoing chemotherapy, in AIDS patients during therapy, and in patients after bone marrow transplantation. Interestingly, the hematopoietic system of GM-CSF-deficient mice appears to be normal; the most significant changes are in some specific T cell responses. Although molecular cloning of GM-CSF was carried out using cDNA library oft cells and it is well known that the T cells produce GM-CSF after activation, there is a lack of systematic investigation of this cytokine in production by T cells and its effect on T cell function. In this article, we will focus mainly on the immunobiology of GM-CSF in T cells.

IL-23 signaling enhances Th2 polarization and regulates allergic airway inflammation

IL-23/IL-17 axis is an important regulator in various inflammatory diseases. However, the role of IL-23 in allergic airway inflammation is not well understood. In this study, we show that in an allergen-induced asthma model, mice with transgenic overexpression of IL-23R exhibited increased airway infiltration of eosinophils and Th2 cytokine production, whereas those deficient in IL-23 displayed reduced airway inflammation. In vitro, IL-23-IL-23R signaling promoted GATA-3 expression and enhanced Th2 cytokine expression. Conversely, in the absence of this signal, Th2 cell differentiation was partially inhibited. Therefore, IL-23 signaling may regulate allergic asthma through modulation of Th2 cell differentiation.

Preparation, optical properties and cell staining of water soluble amine-terminated PAMAM G2.0-Au nanocomposites

The solution chemical and optical characteristics of formation of amine-terminated polyamidoamine dendrimer G2.0（NH2-PAMAM G2.0）-Au nanocomposites in the aqueous solution of NH2-PAMAM G2.0 at various mole ratios of Au（Ⅲ） to NH2-PAMAM G2.0 were studied by both UV-visible spectrometry and fluorospectrometry. The NH2-PAMAM G2.0-Au nanocomposites, with a type of structure in which one Au nanoparticle is surrounded by several NH2-PAMAM G2.0 dendrimers, emit strong bluish violet fluorescence, and are uniform, water soluble and biocompatible as well as very stable in frozen conditions. The size of gold nanoparticles in the nanocomposites is about 2.5 nm and decreases with the increase of NH2-PAMAM G2.0 concentration. The NH2-PAMAM G2.0 plays an important role in acting as host or micro-reactor for Au（Ⅲ） before Au（Ⅲ） reduction and acting as dispersant and stabilizer for gold nanoparticles after Au（Ⅲ） reduction. Preliminary experiments of cells staining to human embryonic lung fibroblast cell lines show that the NH2-PAMAM G2.0-Au nanocomposites can be used as optical imaging markers for bioanalyses and medical diagnoses.

Influence of Copper Stress on Ultra-structure of Wheat Seedlings

Transmission Electron Microscope (TEM) Technology was used to investigate the effect of 25,100 and 200 mg/kg copper on ultra-structure of root tip and leaf blade of wheat. Result showed that serious damage was found with Copper of 25,100 and 200 mg/kg. Plasmolysis,concentrated cytoplasm,chloroplast inflation,lamellar structure disturbance,capsule disappearance and disintegration,mitochondria structures ambiguity and vacuolization were all symptoms under Cu stress. There were positive correlation between concentration of coper stress and the degree of injury,and the degree of injury of copper were different in different organelles. Mitochondria were the most sensitive organelles,and there was patient difference in the same organelles of different parts.

Galactosylated chitosan/5-fluorouracil nanoparticles inhibit mouse hepatic cancer growth and its side effects

AIM： To observe the curative effect of galactosylated chitosan （GC）/5-fluorouracil （5-FU） nanoparticles in liver caner mice and its side effects. METHODS： The GC/5-FU nanoparticle is a nanomate- rial made by coupling GC and 5-FU. The release experiment was performed in vitro. The orthotropic liver cancer mouse models were established and divided into control, GC, 5-FU and GC/5-FU groups. Mice in the control and GC group received an intravenous injection of 200 μL saline and GC, respectively. Mice in the 5-FU and GC/5-FU groups received 200 μL （containing 0.371 mg 5-FU） 5-FU and GC/5-FU, respectively. The tumor weight and survival time were observed. The cell cycle and apoptosis in tumor tissues were monitored by flow cytometry. The expression of p53, Bax, Bcl-2, caspase-3 and poly adenosine 50-diphosphate-ribose polymerase 1 （PARP-1） was detected by immunohistochemistry, reverse transcription-polymerase chain reaction and Western blot. The serum blood biochemical parameters and cytotoxic activity of natural killer （NK） cell and cy- totoxicity T lymphocyte （CTL） were measured. RESULTS： The GC/5-FU nanoparticle is a sustained release system. The drug loading was 6.12% ± 1.36%, the encapsulation efficiency was 81.82% ± 5.32%, and the Zeta potential was 10.34 ± 1.43 mV. The tu- mor weight in the GC/5-FU group （0.4361±0.1153 g vs 1.5801 ± 0.2821 g, P 〈 0.001） and the 5-FU （0.7932±0.1283 g vs 1.5801 ±0.2821 g, P 〈 0.001） was sig- nificantly lower than that in the control group; GC/5- FU treatment can significantly lower the tumor weight （0.4361± 0.1153 g vs 0.7932±0.1283 g, P 〈 0.001）, and the longest median survival time was seen in the GC/5-FU group, compared with the control （12 d vs 30 d, P 〈 0.001）, GC （13 d vs 30 d, P 〈 0.001） and 5-FU groups （17 d vs 30 d, P 〈 0.001）. Flow cytom- etry revealed that compared with the control, GC/5- FU caused a higher rate of G0-G1 arrest （52.79% ± 13.42% vs 23.92%±9.09%, P = 0.014 ） and apopto- sis （2.55% ±1.10% vs 11.13% ±11.73%, P 〈 0.001） in hepatic cancer cells. Analysis of the apoptosis path- ways showed that GC/5-FU upregulated the expression of p53 at both the protein and the mRNA levels, which in turn lowered the ratio of Bcl-2lBax expression; this led to the release of cytochrome C into the cytosol from the mitochondria and the subsequent activation of caspase-3. Upregulation of caspase-3 expression de- creased the PARP-1 at both the mRNA and the protein levels, which contributed to apoptosis. 5-FU increased the levels of aspartate aminotransferase and alanine aminotransferase, and decreased the numbers of platelet, white blood cell and lymphocyte and cytotoxic activities of CTL and NK cells, however, there were no such side effects in the GC/5-FU group. CONCLUSION： GC/5-FU nanoparticles can significant- ly inhibit the growth of liver cancer in mice via the p53 apoptosis pathway, and relieve the side effects and im- munosuppression of 5-FU.

ONCOGENIC TRANSFORMATION OF SYRIAN HAMSTER EMBRYO CELLS BY 5．3－MeV α PARTICLES AND A TUMOR PROMOTER PHORBOL ESTER

The primary Syrian hamster embryo(SHE) cells were used to study the oncogenic transformation by ￣(238)pu α particles or X-rays alone or in combination with a chemical promoter phorbol ester.Survival curves of SHE cells following exposure to α-particles or X-rays were fitted to single-or multi-target models,respectively. Model parameters were: Do = 0. 55 Gy. n = 1 for α particles 4 Do = 1.44 Gy. Dq = 3.0 Gy. n=7.7 for X-rays.Incidence of α particles or X-rays induced cell transformation was dose-dependant.α particles were more efficient in inducing cell transformation than that of X-rays. The enhancement of SHE cell transformation by phorbol 12-myristate 13-acetate(PMA) following exposure to α particles of 0. 25-1. 00 Gy was observed.

Thansgenic peanut plants obtained by particle bombardment via somatic embryogenesis regeneration system

After pre-culture and treatment of osmosis, cotyledons of immature peanut (Arachis hypogaea L.) zygotic embryos were transformed via particle bombardment with a plasmid containing a chimeric hph gene conferring resistance to hygromycin and a chimeric intron-gus gene. Selection for hygromycin resistant calluses and somatic embryos was initiated at 10th d post-bombardment on medium containing 10-25 mg/L hygromycin. Under continuous selection, hygromycin resistant plantlets were regenerated from somatic embryos and were recovered from nearly 1.6% of the bombarded cotyledons. The presence and integration of foreign DNA in regenerated hygromycin resistant plants was confirmed by PCR (polymerase chain reaction) for the intron-gus gene and by Southern hybridization of the hph gene. GUS enzyme activity was detected in leaflets from transgenic plants but not from control, non-transformed plants. The production of transgenic plants are mainly based on a newly improved somatic embryogenesis regeneration system developed by us.

Molecular mechanisms of apoptosis induced by Scorpio water extract in human hepatoma HepG2 cells

AIM: To clarify the mechanism underlying the anti-mutagenic and anti-cancer activities of Scorpio water extract (SWE). METHODS: Human hepatoma HepG2 cells were incubated with various concentrations of SWE. After 24-h incubation, cytotoxicity and apoptosis evaluations were determined by MTT and DNA fragmentation assay, respectively. After treatment with SWE, mitochondrial membrane potential (MMP) was determined by measuring the retention of the dye 3,3'-dihexyloxacarbocyanine (DiOC6(3)) and the protein expression including cytochrome C and poly-(ADPribose) polymerase (PARP) were measured by Western blotting. Caspase-3 and -9 enzyme activities were measured using specific fluorescence dyes such as Ac-DEVD-AFC and Ac-LEHD-AFC. RESULTS: We found that treatment with SWE induced apoptosis as confirmed by discontinuous DNA fragmentation in cultured human hepatoma HepG2 cells. Our investigation also showed that SWE-induced apoptosis of HepG2 cells were associated with intracellular events including disruption of MMP, increased translocation of cytochrome C from mitochondria to cytosol, activation of caspase-3, and PARP. Pre-treatment of N-acetyl-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO), a caspase-3 specific inhibitor, or cyclosporin A (CsA), an inhibitor of MMP disruption, completely abolished SWE-induced DNA fragmentation. CONCLUSION: These results suggest that SWE possibly causes mitochondrial damage, leading to cytochrome C release into cytosol and activation of caspases resulting in PARP cleavage and execution of apoptotic cell death in HepG2 cells. These results further suggest that Scorpio may be a valuable agent of therapeutic intervention of human hepatomas.

Controlling Beam Halo-Chaos via Time-Delayed Feedback

The study of controlling high-current proton beam halo-chaos has become a key concerned issue for manyimportant applications. In this paper, time-delayed feedback control method is proposed for beam halo-chaos. Particle incell simulation results show that the method is very effective and has some advantages for high-current beam experimentsand engineering.

Changes of Circulating Platelet-Derived Growth Factor and Granulocyte Colony-Stimulating Factor in Patients with Condyloma Acuminatum

Objective: To study the expression levels of platelet-derived growth factor (PDGF) and granulocyte colony-stimulatingfactor (G-CSF) in peripheral blood and their role in thepathogenesis of Condyloma acuminatum (CA). Methods: Sera were taken from 70 patients with Condylomaacuminatum and compared with 35 healthy controls. PDGFand G-CSF in serum were quantitated using a dual antibodysandwich enzyme-linked immunoabsorbent assay (ELISA). Results: Serum concentrations of PDGF and G-CSF weresignificantly increased in patients with Condylomaacuminatum (CA) compared to controls (P<0.001 and P<0.005respectively). Serum levels of PDGF and G-CSF correlatedwith clinical severity of CA, but no significant difference wasobserved between different duration of disease groups. Asignificant positive correlation was noticed between neutrophilcount and G-CSF levels (γ=0.38, P<0.001), and the neutrophilcount showed no significant correlation with PDGE Conclusion: The results indicated that increased expressionof PDGF an -CSF in peripheral blood might be involved in pathogenesis of CA.