Neutrophils and neutrophil extracellular trap components: Emerging biomarkers and therapeutic targets for age-related eye diseases

Age-related eye diseases, including dry eye, glaucoma, age-related macular degeneration, and diabetic retinopathy, represent a major global health issue based on their increasing prevalence and disabling action. Unraveling the molecular mechanisms underlying these diseases will provide novel opportunities to reduce the burden of age-related eye diseases and improve eye health, contributing to sustainable development goals achievement. The impairment of neutrophil extracellular traps formation/degradation processes seems to be one of these mechanisms. These traps formed by a meshwork of DNA and neutrophil cytosolic granule proteins may exacerbate the inflammatory response promoting chronic inflammation, a pivotal cause of age-related diseases. In this review, we describe current findings that suggest the role of neutrophils and their traps in the pathogenesis of the above-mentioned age-related eye diseases. Furthermore, we discuss why these cells and their constituents could be biomarkers and therapeutic targets for dry eye, glaucoma, age-related macular degeneration, and diabetic retinopathy. We also examine the therapeutic potential of some neutrophil function modulators and provide several recommendations for future research in age-related eye diseases.     

连续性肾脏替代治疗联合中药灌肠对急性肾损伤患者尿KIM-1、NGAL水平的影响

目的:探讨连续性肾脏替代治疗(CRRT)联合中药灌肠对重症急性肾损伤患者尿肾损伤分子-1(KIM-1)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平和预后的影响。方法:回顾性分析89例重症急性肾损伤患者临床资料,依据不同治疗方式分为对照组43例和研究组46例,对照组采用CRRT治疗,研究组采用CRRT联合中药灌肠治疗。比较两组尿量恢复时间、重症医学科(ICU)住院时间、治疗前后肾功能、尿KIM-1、NGAL水平,序贯器官衰竭估计评分(SOFA)、急性生理与慢性健康评分表(APACHEⅡ)评分和预后情况。结果:研究组尿量恢复时间、ICU住院时间均少于对照组(P<0.05)。治疗前,两组肾功能、尿KIM-1、NGAL水平,SOFA、APACHEⅡ评分比较,差异无统计学意义(P>0.05); 治疗后,两组肾功能指标、尿KIM-1、NGAL水平,SOFA、APACHEⅡ评分均较治疗前下降,研究组低于对照组,差异有统计学意义(P<0.05)。研究组死亡率较对照组低(P<0.05)。结论:CRRT联合中药灌肠能够促进重症急性肾损伤患者肾功能的恢复,降低尿KIM-1、NGAL水平,改善预后。     

NLR、PLR在高血脂症性急性胰腺炎诊断及病情评估中的价值

目的探究中性粒细胞与淋巴细胞比值(NLR)、血小板与淋巴细胞比值(PLR)在高血脂症性急性胰腺炎(HLAP)诊断及病情评估中的价值。方法选取本院132例HLAP患者作为观察组,另选取同期66例胆源性、酒精性急性胰腺炎非HLAP患者作为对照组,66例健康体检者作为健康组,比较3组NLR、PLR、血脂指标[总胆固醇(TC)、三酰甘油(TG)]、炎性因子[C反应蛋白(CRP)、降钙素原(PCT)],分析NLR、PLR与血脂指标、炎性因子相关性,采用受试者工作特征(ROC)曲线评价NLR、PLR诊断价值,对比观察组不同病情程度患者NLR、PLR水平,分析NLR、PLR与HLAP病情程度的关系。结果观察组NLR、PLR、TC、TG、CRP、PCT高于对照组、健康组,对照组高于健康组,差异有统计学意义(P<0.05);Pearson相关性分析,NLR、PLR与TC、TG、CRP、PCT呈正相关(P<0.05);ROC曲线分析,NLR、PLR联合诊断AP的AUC为0.901,95%CI为0.858~0.934,敏感度为80.30%,特异度为92.42%,两者联合诊断HLAP的AUC为0.846,95%CI为0.788~0.893,敏感度为71.21%,特异度为83.33%,均优于两者单独诊断,差异有统计学意义(P<0.05);观察组重度患者NLR、PLR高于中度患者、轻度患者,中度患者高于轻度患者,差异有统计学意义(P<0.05);Spearman相关性分析,NLR、PLR与HLAP病情程度呈正相关(P<0.05)。结论 NLR、PLR联合检测在HLAP诊断与病情评估中具有较高临床价值。     

中性粒细胞与淋巴细胞比值对三阴性乳腺癌临床预后及与Ki - 67表达的影响

目的 探讨中性粒细胞与淋巴细胞比值（neutrophil to lymphocyte ratio，NLR）对三阴性乳腺癌的临床预后影响及与Ki - 67表达的关系。方法 回顾性分析2006年1月 - 2012年12月于我院乳腺外科住院治疗的134例三阴性乳腺癌患者。NLR最佳临床分界值采用ROC曲线确定，并依此分NLR＜2.64组和NLR≥2.64组。临床独立预后因素采用单因素和多因素Cox回归模型分析。术后生存时间和生存曲线比较采用Kaplan - Meier和log - rank方法。Ki - 67的表达采用免疫组织化学方法检测。结果 NLR是三阴性乳腺癌的独立预后因素，最佳临界值为2.64。NLR＜2.64组术后中位DFS为39.10月，中位OS为52.30月；NLR≥2.64组术后中位DFS为27.35月，中位OS为37.35月。2组术后DFS和OS比较，差异具有统计学意义（P＜0.05）。NLR低组伴Ki - 67表达阴性的三阴性患者术后中位DFS和OS生存时间显著高于其他情况。结论 NLR是三阴性乳腺癌的关键影响预后因素，具有重复性强、非侵袭性、方便实用等特性，可用于预测三阴性乳腺癌临床预后。     

Vaccination using inactivated Mycoplasma pneumoniae induces detrimental infiltration of neutrophils after subsequent infection in mice

Mycoplasma pneumoniae (Mp) is one of the most common causes of community-acquired pneumonia. Given the emergence and high rates of antibiotic-resistant Mp strains, vaccines that prevent the pneumonia and secondary complications due to Mp infection are urgently needed. Although several studies have shown the protective efficacy of Mp vaccines in human clinical trials, some reports suggest that vaccination against Mp exacerbates disease upon subsequent Mp challenge. Therefore, to develop optimal vaccines against Mp, understanding the immune responses that contribute to post-vaccination exacerbation of inflammation is crucial. Here we examined whether Mp vaccination might exacerbate pneumonia after subsequent Mp infection in mice. We found that vaccination with inactivated Mp plus aluminum salts as an adjuvant induced Mp-specific IgG, Th1 cells, and Th17 cells. Toll-like receptor 2 signaling contributed to the induction of an Mp-specific IgG response and was necessary for Mp-specific Th17-cell—but not Th1-cell—responses in vaccinated mice. In addition, vaccination with inactivated Mp plus aluminum salts suppressed the number of Mp organisms in the bronchoalveolar lavage fluid, indicating that vaccination can reduce Mp infection. However, the numbers of total immune cells and neutrophils in bronchoalveolar lavage fluid after Mp challenge did not differ between vaccinated mice and non-vaccinated control mice. Furthermore, depletion of CD4⁺ T cells prior to Mp challenge decreased pulmonary neutrophil infiltration in vaccinated mice, suggesting that Th1 or Th17 cells (or both) are responsible for the vaccination-induced neutrophil infiltration. These results suggest that, despite reducing Mp infection, vaccination of mice by using inactivated Mp fails to suppress inflammation, such as neutrophil infiltration into the lung, after subsequent Mp infection.     

血清SAA/CRP、CD64对儿童甲型流感早期诊断的临床价值分析

目的探讨血清淀粉酶A蛋白(SAA)与C-反应蛋白(CRP)比值SAA/CRP、中性粒细胞表面抗原CD64对儿童甲型流感早期诊断的临床价值。方法选择2017年8月~2019年2月来医院儿科就诊的125例流感症状患儿作为研究对象,根据患儿临床诊断结果将其分为甲型流感组31例、非甲型流感组94例;再选择同期在天津海河教育园区达文路卫生服务中心健康体检健康儿童30例作为对照组。患儿入组后立即留取鼻咽吸取液,采用RT-PCR鉴定流感病毒型别;采集末梢血进行7项呼吸道病毒联合检测及血清SAA、CRP以及外周血中性粒细胞表面抗原CD64表达水平。结果甲型流感组与非甲型流感组患儿血清SAA、SAA/CRP以及CD64指数显著高于对照组,甲型流感组血清SAA、SAA/CRP以及CD64指数显著高于非甲型流感组,差异均有统计学意义(P<0.05),3组儿童血清CRP水平比较差异无统计学意义(P>0.05)。运用ROC曲线分析在疑似甲型流感125例患儿中血清SAA、CRP、SAA/CRP以及CD64对甲型流感诊断价值,结果显示各指标诊断曲线下面积分别为0.908、0.641、0.994、0.957。结论甲型流感患儿血清SAA、SAA/CRP以及中性粒细胞表面受体CD64表达显著升高,在甲型流感患儿的早期临床诊断中具有较高的辅助价值。     

支气管哮喘患儿中性粒细胞胞外诱捕网水平与患者免疫功能及临床预后的关系

目的探讨支气管哮喘患儿中性粒细胞胞外诱捕网水平与患者免疫功能及临床预后的关系。方法选取本院2017年9月-2018年9月支气管哮喘患者80例作为观察组,并以同期健康体检的30例儿童作为对照组,采用pico Green dsDNA荧光染色定量检测支气管哮喘患者NETs水平,采用T淋巴细胞亚群评价患者免疫功能,对比不同NETs水平患者免疫功能及临床特点,采用Logistic回归分析探讨小儿支气管哮喘急性发作的风险因素。结果观察组白细胞、中性粒细胞、单核细胞、Cf-DNA/NETs水平均高于对照组(P <0. 05),而淋巴细胞水平低于对照组,差异均有统计学意义(P <0. 05)。Logistic回归分析显示,哮喘家族史、呼吸道感染、Cf-DNA/NETs水平上升、有害气体接触、被动吸烟均是支气管哮喘急性发作的独立危险因素(P <0. 05)。结论中性粒细胞胞外诱捕网水平与支气管哮喘患者免疫功能及预后密切相关,值得临床重点关注。     

中性粒细胞明胶酶相关载脂蛋白、肾损伤分子-1及胱抑素-C对ICU脓毒症患者并发急性肾损伤的诊断效能

目的探讨中性粒细胞明胶酶相关载脂蛋白(NGAL)、肾损伤分子-1(KIM-1)及胱抑素-C(Cys-C)对ICU脓毒症患者并发急性肾损伤(AKI)的诊断效能。方法选择2018—2019年辽宁省人民医院收治的脓毒症患者114例,依据患者是否出现AKI分为损伤组61例和非损伤组53例。以双抗体夹心酶标免疫分析法检测患者不同时间点NGAL、KIM-1和Cys-C水平,评估三者对AKI的诊断效能。结果两组不同时间点NGAL、KIM-1和Cys-C水平差异均有统计学意义(P<0.05)。三种标志物单独检测的诊断效能以KIM-1最佳,三种标志物联合检测的诊断效能优于单一标志物检测。结论血清NGAL、KIM-1和Cys-C均可早期预测脓毒症患者出现AKI,推荐三种标志物联合检测,以提高诊断效能。