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。     

低营养及低氧状态下NIH3T3细胞增殖及细胞周期的变化及对bFGF的影响

目的： 体外模拟慢性创面缺氧、低营养环境，观察成纤维细胞在该状态下增殖及细胞周期的变化及对外源性生长因子（bFGF）的反应,探讨低氧、低营养条件下成纤维细胞的病理生理变化。方法: 单纯缺氧环境采用厌氧培养箱，通入混合气，氧分压（PO₂）分为27 mmHg和44 mmHg 2个水平；低营养环境则控制培养液新生牛血清（NCS）浓度。用MTT法检测细胞活性以及其对外源性生长因子的反应，用流式细胞仪检测细胞周期。结果: PO₂ 44 mmHg时细胞增殖速度较同期对照组无明显差异；PO₂ 27 mmHg时，细胞增殖速度较同期对照组明显减慢（P<0.01），细胞被阻滞于G₀期，S期细胞比例明显减少，bFGF未显示促增殖作用。NCS浓度为0.5%的低营养状态下细胞增殖速度较同期对照组明显减慢（P<0.01），细胞被阻滞于G₀-G₁期（P<0.01）；bFGF能明显改善低营养状态下的增殖减慢（P<0.01），使G₂-M期细胞比例增加（P<0.05）。结论: 27 mmHg PO₂或NCS浓度为0.5%的低营养环境使细胞阻滞于G₀-G₁期，影响成纤维细胞增殖；bFGF可以改善低营养条件下细胞增殖减慢的状态，但对极度缺氧条件下的成纤维细胞增殖障碍无明显作用。     

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...     

热力学模型对石油低压汽液平衡计算的适用性

以Maxwell-Bonnel图拟合式、对比态Antoine方程及Pitzer-Riedel关联式分别求算饱和蒸汽压P^0,并用RoultK值（K＝P^0／P）,计算窄留分K值。根据实测的中原、孤岛和克拉玛依石油馏分低压K值,考察上述三式,结果表明：对比态Antoine式预测精度是最好的,其温度预测绝对平均偏差为7．0℃,K值预测平均相对偏差为15．6％,其他两模型偏差均较大。     

腹膜透析相关性腹膜炎兔模型的病理形态学观察

用 12只新西兰大白兔分为腹膜炎组和对照组。腹膜炎组注射含活金黄色葡萄球菌的透析液 ,对照组为含生理盐水的透析液 ;观察腹膜透析相关性腹膜炎兔模型的病理变化。结果发现 :(1)腹膜炎组腹膜间皮细胞增生 ,水肿 ,血管扩张 ,炎症细胞浸润 ,对照组无变化。 (2 )腹膜炎组腹膜透液中葡萄糖浓度除 0min外 ,其他各时间点D/D0 葡萄糖均低于对照组 (P <0 .0 1)。 (3)腹膜炎组腹透液中肌酐浓度与血浆肌酐浓度比值 (D/Dcr)显著高于对照组中的浓度比值 (P <0 .0 5 )。 (4 )腹膜炎组透析液中WBC计数除O点外 ,其余各时间点明显高于对照组 (P <0 .0 5 )。提示新西兰兔腹膜注射含活金黄色葡萄球菌 48h后 ,进行腹膜透析时 ,其腹膜病理改变与临床腹膜透析并发腹膜炎特征基本一致     

大鼠磨牙三维有限元模型的建立

目的 :建立大鼠磨牙的三维有限元模型 ,探讨牙及牙周组织的应力分布状况。方法 :采用Sprague Dawley大鼠 2 0只 ,建立大鼠磨牙正畸移动的动物模型 ,制作大鼠上颌第一磨牙牙周连续切片 ;采用计算机技术 ,重建牙及牙周组织三维形态、结构 ,并建立其三维有限元模型。结果 :组织切片的应力分布显示牙周膜是一种存在于两种硬组织之间的软组织 ,有其特有的应力分布状态。结论 :本研究建立的正畸大鼠磨牙三维有限元模型是观察正畸牙移动过程中分析应力的一种简便、准确、可靠的模型及方法。     

Effects of diuretics on intradialytic hypotension in maintenance dialysis patients: a systematic review and meta-analysis

Purpose

Intradialytic hypotension (IDH) is a serious complication in dialysis patients. Diuretics might reduce the incidence of IDH by decreasing ultrafiltration. However, the effect of diuretics on IDH in maintenance dialysis patients is still unclear.

Methods

We searched Medline, Embase, the Cochrane Library, China National Knowledge Infrastructure and clinical trials registries from 1945 to May 2019. Randomized controlled trials (RCTs) or observational studies about IDH in maintenance dialysis with diuretics were included.

Results

Seven studies including 28,226 patients were included, of which 4 were RCTs involving mineralocorticoid receptor antagonists (MRAs) and 3 were observational studies involving loop diuretics. There was a trend that a lower incidence rate of IDH in maintenance dialysis patients who used loop diuretics than control, although the result was not statistically significant (OR 0.65, 95% CI 0.34–1.22, P?=?0.18). Similarly, lower incidence rate of all-cause mortality (OR 0.92, 95% CI 0.87–0.99; P?=?0.02) and cardiovascular (CV) mortality (OR 0.86, 95% CI 0.75–0.99, P?=?0.03) in dialysis patients who used loop diuretics than control. On the contrary, there were no significant difference in the incidence of IDH (OR 1.35, 95% CI 0.78–2.34, P?=?0.29) and all-cause mortality (OR 0.73, 95% CI 0.26–2.01; P?=?0.54) and CV mortality (OR 0.57, 95% CI 0.14–2.25; P?=?0.42) in maintenance dialysis patients who used MRAs compared with control.

Conclusion

Loop diuretics, but not MRAs, might have a potential benefit to reduce the incidence rate of IDH, all-cause mortality and CV mortality. More high-quality studies are needed to strengthen the arguments.