p38丝裂原活化蛋白激酶信号途径在鼠破骨细胞生成和骨吸收中的作用

目的研究p38丝裂原活化蛋白激酶(p38MAPK)信号途径在甲状旁腺素相关肽(PTHrP)诱导的破骨细胞生成和骨吸收中的作用。方法取小鼠骨髓细胞,在PTHrP(45ng/ml)的刺激下,在不同试验组中分别入0.1、1.0及10μmol/L的p38MAPK抑制剂Fr167653,继续培养6d。抗酒石酸染色,进行破骨细胞计数。在小鼠颅骨部位注射PTHrP建立骨吸收和高钙血症动物模型。每日给予p38MAPK抑制剂Fr16765330mg/kg,每日2次,X线片观察骨吸收面积,组织学检查计算单位面积内破骨细胞数目,采集血样观察全血内游离钙水平。结果PTHrP刺激下,大量破骨细胞生成(118.9±28.3)个/孔;加入0.1μmol/LFr167653可以部分抑制破骨细胞的生成(79.6±28.0)个/孔,加入10μmol/LFr167653几乎全抑制了破骨细胞生成(7.4±0.4)个/孔,每日给予Fr16765330mg/kg,每日2次,可以明显抑制骨吸收,表现为X线片上骨吸收面积减少,单位面积内破骨细胞数目减少,但是并不能有效地抑制高钙血症。结论抑制p38MAPK信号途径可以抑制破骨细胞的分化和局部骨吸收。     

High-performance water-borne fluorescent acrylic-based adhesive: synthesis and application

Water-borne adhesives have immense importance in cellulose-based materials, where their durability, handling, and strength remain to be a major concern. The present work demonstrates the development of three water-borne adhesives, namely, poly(1-vinyl-2-pyrrolidone-co-acrylic acid), poly(acrylonitrile-co-acrylic acid), and poly(1-vinyl-2-pyrrolidone-co-acrylonitrile-co-acrylic acid) applicable for cellulose-based materials. These acrylic-acid based adhesives were characterized by Fourier-transform infra-red spectroscopy, thermogravimetric analysis, X-ray diffraction, gel permeation chromatography, and universal testing machine. The synthesized polymer adhesives can be stored in the powder form for a longer period, thus utilizing less space. In order to use as adhesives, suitable formulations can be prepared in water. The adhesives show thermal stability up to 300 °C. Our studies show that poly(1-vinyl-2-pyrrolidone-co-acrylonitrile-co-acrylic acid) showed higher lap shear strength (ASTM D-906) than commercially available adhesives. In addition, these adhesives, being fluorescent in nature, can be detected under UV light and thus are applicable for the detection of fractured joints of any specimen. This property also helps in anti-counterfeiting applications, thus adding further to their utility.

Synthesis and application of a water-borne fluorescent acrylic adhesive, which can be stored as a powder for long-term use.     

Impact of intensified chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical routine in Europe

Background

Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma (MPA). Randomized clinical trials evaluating intensified chemotherapies including FOLFIRINOX and nab-paclitaxel plus gemcitabine (NAB+GEM) have shown improvement in survival. Here, we have evaluated the efficacy of intensified chemotherapy versus gemcitabine monotherapy in real-life settings across Europe.

Existence of a pool of T-lymphocyte colony-forming cells (T-CFC) in human bone marrow and their place in the differentiation of the T- lymphocyte lineage

The existence and characteristics of bone marrow T-cell progenitors have not yet been established in man. Several pieces of evidence such as the reconstitution of certain immunodeficiencies by bone marrow graft suggest that T-cell precursors are present in the bone marrow. We report the growth of T-cell colonies from bone marrow populations using PHA-stimulated lymphocyte-conditioned medium containing T-cell growth factor (TCGF). Rosetting experiments and complement-dependent cytotoxicity assays with monoclonal antibodies indicate that the bone marrow T colony-forming cells (T-CFC) are E- OKT 3- and la+, i.e., immature progenitors. The colonies derived from these cells have the phenotype of mature T cells: E + OKT 3 + la- with either helper (OKT 4+) and suppressor (OKT 8 +) antigens. These results suggest that a thymic microenvironment may not be necessary for the in vitro proliferation and differentiation of the T-cell lineage in adult humans. These methodologies may permit direct investigation of early phenomena concerning the T-cell lineage, such as the acquisition of self-tolerance, the formation of a repertoire of specificities, and the HLA restriction phenomena that we believe takes place before the thymic maturation.     

Minor histocompatibility antigens HA-1-, -2-, and -4-, and HY-specific cytotoxic T-cell clones inhibit human hematopoietic progenitor cell growth by a mechanism that is dependent on direct cell-cell contact

HLA-identical bone marrow transplantation (BMT) may be complicated by graft-versus-host disease or graft rejection. Both complications are thought to be initiated by recognition of minor histocompatibility (mH) antigens by HLA-restricted mH-antigen-specific T lymphocytes. Using HLA- A2-restricted mH antigens HA-1-, -2-, and -4-, and HY-specific cytotoxic T lymphocyte (CTL) clones, we studied the recognition by these CTL clones of interleukin-2 (IL-2)-stimulated T cells (IL-2 blasts), BM mononuclear cells (BMMNCs), and hematopoietic progenitor cells (HPCs). We showed that, when IL-2 blasts from the BM donors who were investigated were recognized by the HA-1-, -2-, and -4-, and HY- specific CTL clones, their BMMNCs and HPCs were recognized as well by these CTL clones, resulting in antigen-specific growth inhibition of erythrocyte burst-forming units (BFU-E), colony-forming units- granulocyte (CFU-G), and CFU-macrophage (CFU-M). the HA-2-specific CTL clone, however, inhibited BFU-E and CFU-G growth from four donors to a lesser extent than from two other donors. We further investigated whether inhibitory cytokines released into the culture medium by the antigen-specific stimulated CTLs or by stimulated BMMNCs were responsible for suppression of HPC growth or whether this effect was caused by direct cell-cell contact between CTLs and HPCs. HPC growth inhibition was only observed after preincubation of BMMNCs and CTLs together for 4 hours before plating the cells in semisolid HPC culture medium. When no cell-cell contact was permitted before plating, neither antigen-stimulated CTL nor antigen-nonstimulated CTLs provoked HPC growth inhibition. Culturing BMMNCs in the presence of supernatants harvested after incubation of BMMNCs and CTL clones together for 4 or 72 hours did also not result in HPC growth inhibition. Both suppression of HPC growth and lysis of IL-2 blasts and BMMNCs in the 51Cr-release assay appeared to be dependent on direct cell-cell contact between target cells and CTLs and were not caused by the release of inhibitory cytokines into the culture medium by antigen-specific stimulated CTLs or by stimulated BMMNCs. Our results show that mH-antigen-specific CTLs can inhibit HPC growth by a direct cytolytic effect and may therefore be responsible for BM graft rejection after HLA-identical BMT.     

急性阑尾炎多层螺旋CT扫描征象与血清炎性标志物的相关性研究

目的探讨急性阑尾炎多层螺旋CT征象与血清炎性标志物的关系。方法收集2012年1月至2013年12月于同济大学附属杨浦医院经手术病理证实的具有完整临床及影像资料的急性阑尾炎患者66例,对所有患者的急性阑尾病变程度行CT分级,分析其与患者白细胞(WBC)计数、中性粒细胞百分比(NEUT%)及血清C反应蛋白(CRP)水平的相关性。结果急性阑尾炎CT分级与患者WBC计数与CRP水平呈正相关(P0.05),穿孔性阑尾炎患者NEUT%及CRP水平明显高于其他患者。CRP水平与阑尾直径、阑尾积液、回盲部变化、阑尾周围炎性条纹、小肠积液呈正相关(P0.05),WBC计数与回盲部变化及阑尾周围炎性条纹呈正相关(P0.05)。结论WBC计数及CRP水平与急性阑尾炎CT分级有关,CRP对急性阑尾炎的诊断及其严重程度的判断更有优势;CRP、NEUT%是穿孔性阑尾炎的重要预测因子,WBC可以更好地发现早期阑尾周围的炎性反应,综合分析CT表现与血清炎性标志物能更准确地诊断急性阑尾炎。