含银介孔二氧化硅-壳聚糖复合材料的制备与性能研究

目的探讨含银介孔二氧化硅-壳聚糖复合材料(Ag/MSN-Chi)的制备方法及其微观表征、细胞毒性、吸水性能、抗菌性能及止血性能。 方法以正硅酸乙酯为前驱体，十六烷基三甲基溴化铵为致孔剂，采用离子交换法在介孔二氧化硅纳米粒子(MSN)中引入银离子，制备出具有抗菌作用的新型有序的含银介孔二氧化硅纳米粒子(Ag/MSN)材料。再利用烷基化壳聚糖负载Ag/MSN，制备出Ag/MSN-Chi。根据所用材料不同将实验分为实验组和空白对照组，实验组又分为3个亚组：MSN组、Ag/MSN组、Ag/MSN-Chi组，空白组为不加任何材料的阳性对照。计算MSN和Ag/MSN的比表面积、孔容、孔径和Ag/MSN与Ag/MSN-Chi的电荷。并通过吸水实验、体外凝血实验、抗菌实验对MSN、Ag/MSN和Ag/MSN-Chi的细胞毒性、吸水性能、止血性能及抗菌性能进行评价，计算细胞相对存活率、吸水率、凝血酶原时间(PT)、凝血活酶时间(APTT)及抑菌率。取健康成年新西兰大白兔18只，随机分成3组：对照组(采用医用纱布处理)、Ag/MSN组(采用Ag/MSN处理)、Ag/MSN-Chi组(采用Ag/MSN-Chi处理)，每组6只，建立肝创伤出血模型，计算止血时间。数据比较采用方差分析和t检验。 结果MSN的比表面积为(523.8±12.4) m²/g、孔容为(1.2±0.4) m³/g、孔径为(3.5±0.9) nm；Ag/MSN的比表面积为(521.6±11.7) m²/g、孔容为(1.15±0.5) m³/g、孔径为(3.6±0.7) nm，2种材料的比表面积、孔容、孔径比较差异均无统计学意义(t＝0.224、0.135、0.015，P值均大于0.05)。经测量，Ag/MSN的Zeta电位为－19.7 mV，Ag/MSN-Chi的Zeta电位为10.27 mV，表明Ag/MSN表面电荷从负值变为正值。Ag/MSN-Chi组、Ag/MSN组和MSN组与小鼠成肌细胞共培养1、4、7 d的细胞相对存活率比较，差异均无统计学意义(F＝2.61、4.72、3.52, P值均大于0.05)。Ag/MSN组吸水率分别与MSN组和Ag/MSN-Chi组比较，差异均无统计学意义(t＝0.482、1.159，P值均大于0.05)。经检测，Ag/MSN-Chi组、Ag/MSN组、MSN组和空白对照组的PT比较，差异无统计学意义(F＝10.28，P>0.05)；Ag/MSN-Chi组、Ag/MSN组、MSN组和空白对照组APTT分别为(20.9±2.1)、(28.5±3.4)、(31.4±2.6)、(38.7±2.5) s，4组比较差异有统计学意义(F＝8.70，P<0.05)；Ag/MSN-Chi组、Ag/MSN组、MSN组APTT分别与空白对照组比较，差异均有统计学意义(t＝9.443、4.186、3.506，P值均小于0.05)；Ag/MSN-Chi组APTT与Ag/MSN组比较，差异有统计学意义(t＝3.294，P<0.05)。MSN组在培养0.5、2、4、6、24 h 5个时间点抑菌率比较差异无统计学意义(F＝5.437，P>0.05)；培养0.5 h，Ag/MSN组和Ag/MSN-Chi组抑菌率分别为(99.7±5.2)%、(97.1±5.4)%，与培养0.5 h MSN组抑菌率(11.2±5.8)%比较，差异均有统计学意义(t＝19.678、18.775, P值均小于0.05)；培养24 h，Ag/MSN组和Ag/MSN-Chi组抑菌率分别为(73.2±5.1)%和(72.9±6.9)%，与MSN组(11.8±5.7)%比较，差异均有统计学意义(t＝13.904、11.825, P值均小于0.05)。Ag/MSN-Chi组、Ag/MSN组和对照组止血时间分别为(12.3±1.5)、(17.2±3.4)、(28.1±3.8) s，3组比较差异有统计学意义(F＝5.892，P<0.05)；Ag/MSN-Chi组和Ag/MSN组止血时间分别与对照组比较，差异均有统计学意义(t＝9.473、5.236, P值均小于0.05)；且Ag/MSN-Chi组与Ag/MSN组止血时间比较，差异有统计学意义(t＝3.230，P<0.05)。 结论Ag/MSN-Chi在不增加细胞毒性的基础上具有有较好的吸水性能、止血性能及抗菌性能。     

基于椭圆方程的三维心脏超声图像的位移场估计

三维超声心动图技术能使医生直观地看到心脏整体和各部分的运动，在临床得到重视。在三维超声心动图技术中，如何定量的描述心脏中某个组织的运动状况极具临床意义。本研究提出了一种基于椭圆偏微分方程的二尖瓣三维运动估计方法。该方法直接在三维超声图像的位移场上进行了运动估计，避免了传统运动估计方法，如光流法，需要标定的缺点。本研究首先建立一个二次误差指标函数，然后利用变分法导出了三维空间下的一组椭圆型偏微分方程。这类方程有着比较成熟的数值解法，利用了有限差分法，对多个三维超声数据立方体进行了计算，结果证明这类方法是有效的。     

多发性骨髓瘤患者血清IL-6活性与急性相蛋白浓度的相关性研究

运用敏感的B_9细胞增殖试验检测了81例多发性骨髓瘤(MM)患者血清IL-6活性,同时分析了标本的几种急性相蛋白含量,结果表明,68％MM患者血清中IL-6活性大于5μ/ml(正常对照为5μ/ml以下),几种急性相蛋白中C-反应性蛋白(CRP)在MM时升高(P<0.01),平均达正常对照组的17倍以上,MM患者补体C_4与正常对照组无差异(p>0.05),C_3、白蛋白及转铁蛋白在MM时分别比正常下降24.42％、38.83％和32.80％,且与疾病分期有关,在血清IL-6大于5μ/ml的55例中,IL-6活性与CRP、C_3、白蛋白的相关系数分别为0.46,-0.34和-0.29,IL-6与转铁蛋白浓度相关不明显。本文结果提示:CRP、C_3及白蛋白等含量的变化可作为反映MM病情的简易而敏感的指标。     

Favorably tipping the balance between cytopathic and regulatory T cells to create transplantation tolerance

Therapeutic application of broadly reactive anti-T cell antibodies can lead not only to potent immunosuppression but also to profound and long-lived T cell depletion. We reasoned that a strategy that almost exclusively targets activated cytopathic donor reactive T cells and spares immunoregulatory networks might prove to be an exceptionally potent and highly selective means of producing long-term engraftment and tolerance. Herein we show that the combined administration of rapamycin and agonist IL-2- and antagonist IL-15-related cytolytic fusion proteins provides for long-term engraftment/tolerance in exceptionally stringent allotransplant models by (1) limiting the early expansion of activated T cells, (2) preserving and even exaggerating their subsequent apoptotic clearance, and (3) further amplifying the depletion of these activated T cells by antibody-dependent mechanisms, while (4) preserving CD4+CD25+ T cell-dependent immunoregulatory networks.     

Fas蛋白在糖尿病大鼠局灶性脑缺血再灌注损伤后海马区的表达及意义

目的探讨Fas蛋白在糖尿病大鼠脑缺血再灌注海马区神经元损伤中的表达及意义。方法健康雄性Wister大鼠60只,随机分为4组:①正常对照组,②假手术组,③脑缺血再灌注组(NIR),④糖尿病脑缺血再灌注组(DIR组);采用STZ诱导糖尿病和线栓法建立大脑中动脉闭塞(MCAO)模型,HE法观察海马CA1神经元缺失,用免疫组化方法检测Fas在糖尿病大鼠脑缺血再灌注海马神经元损伤中的表达。结果HE染色:正常对照与假手术组未见神经元缺失和细胞凋亡,DIR组与脑缺血再灌注组均见神经元缺失和神经细胞凋亡,而DIR组比脑缺血再灌注组神经元缺失严重(P<0.05)。正常对照与假手术组极少见Fas免疫染色阳性细胞,DIR组与脑缺血再灌注组明显见Fas免疫染色阳性细胞,且DIR组比脑缺血再灌注组多(P<0.05)。结论Fas介导的细胞凋亡可能是糖尿病脑缺血再灌注损伤后海马区神经元损伤的机制之一。     

Interferon-gamma is an autocrine mediator for dendritic cell maturation

Maturation of dendritic cells (DC) is critical for efficient antigen presentation and initiation of an immune response. Interferon-gamma (IFN-gamma) is an important Th1 cytokine. In this study, we investigated the role of IFN-gamma in DC maturation using either IFN-gamma receptor deficient- or IFN-gamma overexpression-models. We showed that immature DC generated in vitro from bone marrow (BM) progenitor cells produced low level of IFN-gamma. After LPS stimulation, DC produced more IFN-gamma, and IFN-gamma productions were at comparable levels among C57BL/6 mice-derived DC (C57BL/6 DC), wild-type 129 mice-derived DC (129 DC) and IFN-gamma receptor deficient 129 mice-derived DC (IFN-gammaR-/-DC). We found that IFN-gammaR-/-DC exhibited decreased expression of CD54, CD86, reduced capacity to secrete IL-1beta and IL-12p70, and impaired capacity to stimulate alloreactive T cells and to drive Th1 differentiation. Transfection of IFN-gamma gene into DC promoted DC to express higher CD40, CD54, CD80, CD86, CCR7 and I-Ab, secrete more IL-1beta and IL-12p70, and more potently activate both CD4 and CD8 T cells. These data suggest that IFN-gamma signaling pathway is important for the maturation of DC in an autocrine fashion.     

Antitumor immune response by CX3CL1 fractalkine gene transfer depends on both NK and T cells

The CX3C chemokine fractalkine (CX3CL1) exists as both a membrane-bound form promoting firm cell-cell adhesion and a soluble form chemoattracting leukocytes expressing its receptor CX3CR1. When adenoviral vector expressing mouse fractalkine (AdFKN) was transduced to the tumor cells, fractalkine was expressed as both membrane-bound form on the tumor cells and soluble form in the supernatant in vitro. Intratumoral injection of AdFKN (1 x 10(9)PFU/tumor) into C26 and B16F10 tumors resulted in marked reduction of tumor growth compared to control (C26: 86.5%, p<0.001; B16F10: 85.5%, p<0.001). Histological examination of tumor tissues revealed abundant infiltration of NK cells, dendritic cells, and CD8(+) T lymphocytes 3 and/or 6 days after treatment with AdFKN. Splenocytes from mice treated by AdFKN developed tumor-specific cytotoxic T cells, and thereby protected from rechallenging with parental tumor cells. Antitumor effects by AdFKN were completely abrogated in both NK cell-depleted mice and CD8(-/-) mice, and partially blocked in CD4(-/-) mice. These data indicated that fractalkine mediates antitumor effects by both NK cell-dependent and T cell-dependent mechanisms. This study suggests that fractalkine can be a suitable candidate for immunogene therapy of cancer because fractalkine induces both innate and adaptive immunity.     

Escherichia coli and Staphylococcus aureus elicit differential innate immune responses following intramammary infection

Staphylococcus aureus and Escherichia coli are among the most prevalent species of gram-positive and gram-negative bacteria, respectively, that induce clinical mastitis. The innate immune system comprises the immediate host defense mechanisms to protect against infection and contributes to the initial detection of and proinflammatory response to infectious pathogens. The objective of the present study was to characterize the different innate immune responses to experimental intramammary infection with E. coli and S. aureus during clinical mastitis. The cytokine response and changes in the levels of soluble CD14 (sCD14) and lipopolysaccharide-binding protein (LBP), two proteins that contribute to host recognition of bacterial cell wall products, were studied. Intramammary infection with either E. coli or S. aureus elicited systemic changes, including decreased milk output, a febrile response, and induction of the acute-phase synthesis of LBP. Infection with either bacterium resulted in increased levels of interleukin 1beta (IL-1beta), gamma interferon, IL-12, sCD14, and LBP in milk. High levels of the complement cleavage product C5a and the anti-inflammatory cytokine IL-10 were detected at several time points following E. coli infection, whereas S. aureus infection elicited a slight but detectable increase in these mediators at a single time point. Increases in IL-8 and tumor necrosis factor alpha were observed only in quarters infected with E. coli. Together, these data demonstrate the variability of the host innate immune response to E. coli and S. aureus and suggest that the limited cytokine response to S. aureus may contribute to the well-known ability of the bacterium to establish chronic intramammary infection.     

The study of tuberculosis outbreak in a high school—Shanghai,China, 2017–2018

Journal of Public Health - To investigate the attack rate of active tuberculosis (TB) cases and detection rate of latent tuberculosis infection (LTBI) cases, and to identify possible factors...