Primed neutrophil infiltrations into multiple organs in child physical abuse cases: A preliminary study

Physical abuse of the elderly induces a massive primed neutrophil infiltration into the lung and liver through chemotaxis by interleukin (IL)-8, similar to cases of traumatic or hemorrhagic shock. Here, we used immunohistochemical analyses to investigate this infiltration in cases of physically abused children. In addition, we examined the expression of neutrophil elastase (NE) as the inflammatory mediator and α1-antitrypsin (AAT) as the elastase inhibitor. The number of neutrophils in the abuse cases was increased significantly in the heart, lung, liver, and kidney, compared with that of control cases. IL-8-positive cells and NE-positive cells in all organs of abuse cases were significantly greater than those in control cases. Large quantities of oxidized AAT, which fails to inactivate NE and results in tissue damage, was detected in the liver of abuse cases. Neutrophil infiltration showed positive correlation with the degree of systemic accumulation of non-fatal injuries caused by repetitive abusive behavior. Although further investigation using more autopsy samples is necessary, results of our preliminary study indicate that massive neutrophil infiltration induced by IL-8 in multiple organs is a new complementary diagnostic indicator of physical abuse in children. Moreover, the demonstration of NE-positive cells and oxidized AAT provides firm evidence of tissue damage.     

阿托伐他汀对大鼠脑缺血再灌注后梗死灶周围中性粒细胞浸润和核转录因子-κB表达水平的影响

目的 观察阿托伐他汀对大鼠脑缺血再灌注后梗死灶周围中性粒细胞浸润以及核转录因子-κB表达水平的影响.方法 采用常规尼龙线栓法制备SD大鼠脑缺血再灌注模型,并将大鼠随机分为假手术组、大脑中动脉阻断再灌注(Middle cerebral artery occlusion/reperfusion,MCAO/R)(对照)组和M...     

Lipocalin 2 is a novel immune mediator of experimental autoimmune encephalomyelitis pathogenesis and is modulated in multiple sclerosis

Experimental autoimmune encephalomyelitis (EAE) is a widely used animal model of multiple sclerosis (MS), an inflammatory, demyelinating disease of the central nervous system (CNS). EAE pathogenesis involves various cell types, cytokines, chemokines, and adhesion molecules. Given the complexity of the inflammatory response in EAE, it is likely that many immune mediators still remain to be discovered. To identify novel immune mediators of EAE pathogenesis, we performed an Affymetrix gene array screen on the spinal cords of mice at the onset stage of disease. This screening identified the gene encoding lipocalin 2 (Lcn2) as being significantly upregulated. Lcn2 is a multi-functional protein that plays a role in glial activation, matrix metalloproteinase (MMP) stabilization, and cellular iron flux. As many of these processes have been implicated in EAE, we characterized the expression and role of Lcn2 in this disease in C57BL/6 mice. We show that Lcn2 is significantly upregulated in the spinal cord throughout EAE and is expressed predominantly by monocytes and reactive astrocytes. The Lcn2 receptor, 24p3R, is also expressed on monocytes, macrophages/microglia, and astrocytes in EAE. In addition, we show that EAE severity is increased in Lcn2(-/-) mice as compared with wild-type controls. Finally, we demonstrate that elevated levels of Lcn2 are detected in the plasma and cerebrospinal fluid (CSF) in MS and in immune cells in CNS lesions in MS tissue sections. These data indicate that Lcn2 is a modulator of EAE pathogenesis and suggest that it may also play a role in MS.     

Non-steroidal anti-inflammatory drug modulates oxidative stress and calcium ion levels in the neutrophils of patients with primary dysmenorrhea

Primary dysmenorrhea is a common inflammatory disease with an uncertain pathogenesis, although one consistent finding is increased neutrophil activity. We aimed to investigate the effects of a non-steroidal anti-inflammatory drug (NSAID) on oxidative stress and Ca²⁺ levels in neutrophils from patients with primary dysmenorrhea. Blood samples were obtained for neutrophil isolation from six female patients with primary dysmenorrhea (patients) and six healthy female subjects. The NSAID (diclofenac) was taken daily by the patient group for 6 weeks before a second blood sample was taken. Neutrophils isolated after diclofenac treatment were investigated in three settings: (1) after incubation with verapamil and diltiazem (V + D), (2) after incubation with 2-aminoethoxydiphenyl borate (2-APB), and (3) with neither exposure. Neutrophil lipid peroxidation and stimulated intracellular Ca²⁺ levels were higher in the patients than in the controls, although their levels were reduced after six weeks of treatment with diclofenac. Ca²⁺ levels from neutrophils obtained after diclofenac treatment were further decreased after incubation with V + D or 2-APB, compared with those exposed to neither agent. Neutrophil glutathione peroxidase and total antioxidant status were lower in the patients than in the controls and higher post-treatment with diclofenac. Reduced glutathione levels were similar in the control, patient, and treatment groups. In conclusion, we observed the importance of Ca²⁺ influx into the neutrophils and oxidative stress in the pathogenesis of the patients with primary dysmenorrhea. The NSAID diclofenac appeared to provide a protective effect against oxidative stress and Ca²⁺ entry through modulation of neutrophil VGCC and TRP calcium channels.     

Surface Expression of Neutrophil Adhesion Molecules in Pregnant Women at Risk for Hypertensive Complications

Objective: To determine if neutrophil activation is a pathogenetic factor in hypertensive disorders in pregnancy, the neutrophil expression of adhesion molecules was prospectively investigated in pregnant women at risk, prior to the development of hypertensive complications. Methods: Two neutrophil activation parameters, β₂‐integrin (CD11b) and l‐selectin (CD62L), were assessed at admission between 14 and 24 weeks of gestation in 82 pregnant women at risk of preeclampsia and other hypertensive complications. Results were compared to those in 20 healthy normotensive women. Results: Of the 82 women at risk, 23 (28%) developed hypertensive complications: 9 (11%) preeclampsia and 14 (17%) others, such as intrauterine growth restriction (n = 6), fetal or neonatal loss (n = 8), and preterm delivery (≤ 30 weeks of gestation) (n = 8). All pregnancy outcome measures were significantly worse in the patients with complications than in those at risk but without complications or the healthy controls. Expression of β₂‐integrin was significantly higher in early stages of pregnancy in the women who eventually developed complications than the women who did not, P = .019, or the healthy controls, P = .049. Conclusions: Surface expression of β₂‐integrin is increased in pregnant women at risk for hypertensive complications before the clinical manifestations of the disorder.     

新生儿感染性疾病127例临床研究

目的探讨新生儿感染性疾病实验室非特异性指标相关因素的诊断价值。 方法选取2016年7月至2017年7月承德市中心医院NICU收治的127例出生0~3 d的感染性疾病患儿为感染组,103例0~3 d非感染性疾病新生儿为对照组,比较两组新生儿的临床症状、围产期因素以及实验室指标等。 结果与对照组新生儿相比,感染组患儿喂养困难（15.7%）、呼吸困难（30.7%）、呻吟（31.5%）、皮肤黄染（18.1%）和窒息（5%）等初始症状差异均有统计学意义（χ² = 4.136、24.574、33.282、38.039,P均< 0.001）。围产期因素中两组新生儿母亲孕晚期有感染病史和胎膜早破> 18 h两个因素差异有统计学意义（χ² = 10.536、10.717,P均= 0.001）。实验室指标结果显示,两组新生儿C-反应蛋白（CRP）、白细胞计数以及中性粒细胞百分比差异均有统计学意义（t = 2.740、P = 0.008,t = 6.378、P < 0.001,t = 4.860、P < 0.001）。感染组患儿ROC曲线分析显示：CRP、白细胞计数、中性粒细胞百分比最佳截断点分别为8.0 mg/dl、12.65 × 10⁹/L和63.15%,敏感性分别为24.3%、62.2%和68.9%,特异性分别为99.0%、81.2%和84.4%,曲线下面积（AUC）分别为0.544、0.707和0.769;CRP、白细胞计数和中性粒细胞百分比三者联合敏感性为83.8%,特异性为75.0%,曲线下面积（AUC）为0.860,显著高于单项指标。 结论新生儿感染性疾病的发生与多种围产期因素密切相关,以呼吸系统症状为始发临床表现多见。CRP、白细胞计数和中性粒细胞百分比联合诊断可以提高诊断价值。围产期因素、临床表现和实验室指标相结合,有利于早期识别新生儿感染性疾病。     

血清脂质运载蛋白2、骨代谢指标与中年女性骨密度相关性研究

目的 观察血清脂质运载蛋白2 (lipocalin 2,LCN2)、骨代谢指标与中年女性骨密度的相关性。方法 分析253名汉族女性资料,通过双能X线吸收测定法测量其腰椎和股骨颈的骨密度（bone mineral density, BMD）,测量LCN2、I型胶原的羧基末端交联端肽(type I collage cross-linked-telopeptide, CTX)、骨钙蛋白(osteocalcin ,OCN)和肌酸酐(screatinine ,Scr)的血清水平。结果 LCN2与腰椎和股骨颈的BMD呈负相关。LCN2和CTX、OCN、年龄、Scr之间呈显著正相关。调整年龄和Scr后,LCN2、BMDs和OCN之间的相关性消失,但LCN2仍与CTX呈正相关。LCN2的血清浓度在有和没有骨质疏松性骨折的受试者之间没有显示出显著差异。在多变量回归分析中,LCN2是血清CTX变化的主要决定因素之一。结论 在中年女性中,血清LCN2水平、BMD和OCN之间的关系受到年龄和Scr的干扰。虽然LCN2与CTX呈正相关,但相关性非常小。