单核细胞增生李斯特菌L型对小鼠脾脏树突状细胞免疫调节作用影响的研究

  目的  研究单核细胞增生李斯特菌(Listeria monocytogenes, LM)感染对树突状细胞(dendritic cell, DC)免疫功能的影响,探讨细菌型(WT)和L型(L-form)LM对DC的免疫活化能力差异。  方法  将C57BL/6小鼠随机分为对照组、WT组、L-form组,3组小鼠分别经尾静脉感染PBS液、细菌型LM和L型LM,电镜观察脾脏DC超微结构特征;流式细胞术检测小鼠脾脏DC的数量、共刺激分子表达、胞内细胞因子分泌、脾脏T细胞亚群及其活化程度。  结果  透射电镜可观察到对照组小鼠脾脏DC表面有大量丝状伪足,胞浆均匀,细胞核大而偏于一侧;吞噬细菌后,表面丝状伪足减少,胞质内空泡增多;小鼠感染后第1天脾脏中DC绝对值无明显升高或降低(P>0.05),但成熟表型特征性分子表达上调(P < 0.05),L-form感染组DC表面CD80和CD86分子均高于WT组(P < 0.05);小鼠感染LM后TNF-α+DC比例明显升高,L-form感染组分泌TNF-α的DC高于WT组(P < 0.05);感染LM后第7天,3组小鼠脾脏CD4+T细胞和CD8+T细胞在淋巴细胞中所占比例差异均无统计学意义(P>0.05),但L-form组CD69+ T细胞比例高于WT组(P < 0.05)。  结论  L型LM可介导相对高水平的TNF-α,促进DC成熟以增强其抗原递呈的能力。     

CD34+ human marrow cells that express low levels of Kit protein are enriched for long-term marrow-engrafting cells

Using in utero transplantation into fetal sheep, we examined the capability of human bone marrow CD34+ cells fractionated based on Kit protein expression to provide long-term in vivo engraftment. Twelve hundred to 5,000 CD34+ Kit-, CD34+ Kit(low), and CD34+ Kit(high) cells were injected into a total of 14 preimmune fetal sheep recipients using the amniotic bubble technique. Six fetuses were killed in utero 1.5 months after bone marrow cell transplantation. Two fetuses receiving CD34+ Kit(low) cells showed signs of engraftment according to analysis of CD45+ cells in their bone marrow cells and karyotype studies of the colonies grown in methylcellulose culture. In contrast, two fetuses receiving CD34+ Kit(high) cells and two fetuses receiving CD34+ Kit- cells failed to show evidence of significant engraftment. Two fetuses were absorbed. A total of six fetuses receiving different cell populations were allowed to proceed to term, and the newborn sheep were serially examined for the presence of chimerism. Again, only the two sheep receiving CD34+ Kit(low) cells exhibited signs of engraftment upon serial examination. Earlier in studies of murine hematopoiesis, we have shown stage-specific changes in Kit expression by the progenitors. The studies of human cells reported here are in agreement with observations in mice, and indicate that human hematopoietic stem cells are enriched in the Kit(low) population.     

Acute cardiac injury is associated with adverse outcomes,including mortality in COVID-19 patients: A single-center experience

Objectives:To evaluate acute cardiac injury in COVID-19 patients and its association with adverse outcomes including mortality in the United Arab Emirates (UAE) population.Methods:A retrospective study conducted between February and June 2020 in Dubai, UAE, for all laboratory-confirmed Coronavirus disease-19 patients. Demographic, clinical, laboratory, radiological, and clinical outcomes were compared between patients with and without acute cardiac injury.Results:During the study period, 203 patients were included, of which, 44 (21.7%) had evidence of acute cardiac injury. Compared with patients without acute cardiac injury, patients with acute cardiac injury were: older, had more shortness of breath, diabetes, hypertension, and more bilateral airspace shadowing on admission chest radiography. These patients also had a higher neutrophil count, C-reactive protein, procalcitonin, ferritin, D-dimers and lactate dehydrogenase but lower lymphocyte count. Regarding outcomes, these patients had higher intensive care admissions; a higher rate of complications including acute kidney and liver injury, acidosis, septic shock, acute respiratory distress syndrome, needed more mechanical ventilation, and had a significantly higher risk of death.Conclusion:Acute cardiac injury is common among Coronavirus disease-19 patients. These patients present with higher comorbidities, have high inflammatory markers and have greater risk for in-hospital multi-organ damage, need for mechanical ventilation, and death. Prompt full assessment and intervention are recommended.     

Cardiovascular outcomes trials with glucagon-like peptide-1 receptor agonists: A comparison of study designs,populations and results

Despite treatment advances leading to improved outcomes over the past 2 decades, cardiovascular (CV) disease (CVD) remains the leading cause of morbidity and mortality in people with diabetes. People with type 2 diabetes (T2D) have a 2- to 4-fold increased risk of CVD and CV death. Individuals with T2D have not seen the same improvements in CV morbidity and mortality as those without T2D. Given this, it is important to understand the CV impact of drugs used to treat T2D. In patients with T2D, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown a reduction in HbA1c and body weight regardless of their differences in chemical structure and pharmacokinetic variables. Glycaemic efficacy, accompanied by the potential for weight reduction and a low risk of hypoglycaemia, has moved GLP-1 RAs to the first treatment of choice following metformin monotherapy in the latest American Diabetes Association treatment guidelines. Additionally, all GLP-1 RAs have shown CV safety and several have proven CV benefit. GLP-1 RAs have been evaluated in cardiovascular outcomes trials (CVOTs) of varying sizes, designs and patient populations with differing reported effects on CV outcomes. The purpose of this article is to review the completed GLP-1 RA CVOTs with special attention to how their design, size, patient populations and conduct may influence the interpretation of results.