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.     

The role of immunosuppressive agents in the management of severe and refractory immune‐related adverse events

The advent of immune checkpoint inhibitors has improved survival in some types of cancer and brought promising prospects to cancer immunotherapy. Despite their clinical benefits, significant off‐target toxicities resulting from the immune system activation have been observed, namely immune‐related adverse events (irAEs), which pose to clinicians a new challenge of optimal management. With steroids being the mainstay of current management of irAEs, immunosuppressive agents are especially indicated for severe or steroid‐refractory cases, based on current immunopathophysiological knowledge and on extrapolations of treatment options for primary autoimmune disorders. This review focuses on the status and recent clinical progress of immunosuppressive agents in the management of severe and steroid‐refractory irAEs.     

光学相干断层扫描血管成像对玻璃体腔注射雷珠单抗治疗湿性年龄相关性黄斑变性的随访观察

目的 利用光学相干断层扫描血管成像(OCTA)观察雷珠单抗玻璃体腔注射3次+必要时(3+PRN)方案治疗湿性年龄相关性黄斑变性(AMD)的图像特征。方法 选取2016年9月至2017年5月经荧光素眼底血管造影(FFA)、吲哚菁绿血管造影(ICGA)检查确诊且未予治疗的湿性AMD患者8例8只眼,按照3+PRN治疗方案给予玻璃体腔注射雷珠单抗(0.5 mg/0.05 ml)治疗,采用OCTA 6 mm×6 mm范围模式扫描黄斑区视网膜,在患者治疗前,治疗后1、3、6个月进行规律的门诊随访,记录患者最小分辨角对数(logMAR)矫正视力、脉络膜新生血管(CNV)分型、CNV形态特征及变化、黄斑中心凹视网膜厚度(CRT)、黄斑区视网膜外层血流密度(ORVD)及脉络膜毛细血管层血流密度(CCVD)。结果 男性4例4只眼,女性4例4只眼,平均年龄(70.9±10.6)岁;3只眼为Ⅰ型CNV,5只眼为Ⅱ型CNV。治疗前,治疗后1、3、6个月最佳矫正视力(BCVA)分别为0.55(0.33,0.87)、0.35(0.24,0.84)、0.35(0.22,0.58)、0.26(0.10,0.58)logMAR,各组间差异均无统计学意义(P均>0.05);CRT分别为(271.88±91.95)、(204.00±45.78)、(196.00±31.14)、(219.25±71.32)μm,其中,治疗3个月与治疗前差异有统计学意义(t=2.211,P=0.044);ORVD分别为(41.38±2.77)%、(41.73±3.60)%、(42.53±1.95)%、(41.40±2.33)%,各组间差异均无统计学意义(P均>0.05);CCVD分别为(64.38±2.24)%、(64.96±1.39)%、(64.16±1.39)%、(64.63±1.86)%,各组间差异也均无统计学意义(P均>0.05)。相关性分析结果显示,BCVA与CRT(P=0.009, RR=0.457)和CCVD(P=0.001,RR=0.574)显著相关,与ORVD(P=0.093,RR=0.302)不相关。治疗前CNV形态特征,2只眼为团状,2只眼为线条样,2只眼为纠缠错乱状,1只眼为椭圆环形,1只眼为碎片样。治疗1个月,7只眼CNV形态趋于正常化,表现为CNV最大直径减小、断裂/破碎、周边毛细血管丢失、数量和密度下降、所在区域最大横截面积减小;1只眼CNV形态较前恶化,表现为CNV吻合成环、密度增加、最大血管直径增加。治疗3个月,7只眼CNV形态趋于正常化,1只眼较前无明显变化。治疗6个月,5只眼CNV趋于正常化,3只眼恶化。随访中未发现眼内感染或玻璃体内注射的其他并发症。结论 利用OCTA技术观察CNV特征能够评估湿性AMD患者接受雷珠单抗治疗的疗效,可为湿性AMD患者的治疗与随访提供指导。     

散聚汤加味对宫颈癌术后放化疗患者的癌因性疲乏和免疫功能的改善研究

[目的]探讨散聚汤加味改善宫颈癌术后放化疗患者的癌因性疲乏和免疫功能的疗效。[方法]筛选在洛阳解放军534医院行宫颈癌手术后患者共82例作为研究对象,按随机数字表法随机分为对照组和观察组各41例。对照组给予同步放疗+TP化疗方案[紫杉醇(TAX)+顺铂(DDP)]。观察组在对照组基础上给予散聚汤加味治疗,每日1剂,每日2次,连续服用12周。比较两组患者癌因性疲乏评分、毒性反应、T淋巴细胞亚群水平以及血清免疫球蛋白(IgA、IgG、IgM)水平。[结果]治疗12周后,观察组患者的癌因性疲乏(情绪、感觉、行为、认知)评分显著低于对照组(P0.01);观察组患者的消化道反应、膀胱刺激发生率明显少于对照组(P0.05);治疗12周后,观察组患者CD3+、CD3+CD4+以及IgA、IgG、IgM水平显著高于对照组,CD3+CD8+明显低于对照组(P0.01)。[结论]散聚汤加味能改善宫颈癌术后放化疗患者的癌因性疲乏,增强免疫功能,且可降低毒副反应。     

MTDH基因和ATG7基因在结直肠癌中的表达及临床意义

目的探讨异黏蛋白(MTDH)基因和自噬相关基因7 (ATG7)在结直肠癌(CRC)中的表达及临床意义。方法选取66例CRC患者的CRC组织及癌旁组织,比较CRC组织及癌旁组织中的MTDH mRNA和ATG7mRNA的相对表达量;比较不同临床特征CRC患者的CRC组织/癌旁组织MTDH mRNA、ATG7 mRNA的相对表达量;采用受试者工作特征(ROC)曲线分析CRC组织/癌旁组织中MTODH mRNA和ATG7 mRNA对结直肠癌的诊断价值,并分析MTDH mRNA与ATG7 mRNA的相关性。结果 CRC组织中MTDH mRNA和ATG7 mRNA相对表达量显著高于癌旁组织(P <0.01);TNM分期为Ⅲ~Ⅳ和有肝转移的CRC患者中,CRC组织/癌旁组织中的MTDH mRNA和ATG7 mRNA相对表达量均显著高于Ⅰ~Ⅱ期和无肝转移的CRC患者,低分化程度的CRC患者中CRC组织/癌旁组织中的MTDH mRNA和ATG7 mRNA相对表达量最高(P <0.01)。ROC曲线分析结果 CRC组织/癌旁组织中MTDH mRNA、ATG7 mRNA的AUC面积分别是0.934、0.900,诊断敏感度分别为90.91%、89.39%,特异度分别为86.37%、84.35%。Pearson分析结果表明CRC中MTDH的表达与ATG7的表达呈正相关(r=0.372,P=0.002)。结论 CRC组织中MTDH mRNA、ATG7 mRNA的表达高于癌旁组织。CRC组织中MTDH mRNA、ATG7 mRNA与TNM分期、分化程度、伴肝转移相关。CRC组织中MTDH mRNA、ATG7 mRNA具有诊断价值且两者具有正相关。     

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。     

The impact of age on prognosis in patients with gastric cancer: experience in a tertiary care centre

BackgroundGastric cancer (GC) is a leading cause of cancer-related death in the world and most patients have advanced disease upon presentation. The effect of age on prognosis in GC is controversial. We aimed to determine the impact of age on survival in patients with GC.MethodsThis was a retrospective study of the medical records of Lebanese patients diagnosed with GC at the American University of Beirut Medical Center (AUBMC) between 2005 and 2014. Patients were divided into young (<65 years) and older groups (≥65 years). A multivariate analysis was done to determine the independent predictors of survival. Kaplan-Meier method was used for analysis of long-term survival outcomes.ResultsThe sample consisted of 156 patients. The mean age was 62.15 (SD 13.54). Most patients presented with stage 4 disease (62.2%) and poorly differentiated histology (66.4%). The most common symptoms were abdominal pain and weight loss. On bivariate analysis, advanced stage (P=0.02) and higher grade (P=0.04) were associated with increased mortality. Patients <65 years of age were significantly more likely to have poorly differentiated tumours, while patients ≥65 years had more comorbidities (P=0.001). The 5-year DFS were 35% and 37% for patients <65 years of age and ≥65 years of age, respectively (P=0.15).ConclusionsHigher grade and advanced stage are associated with worse survival in patients with GC, but age did not seem to have an impact. Screening high risk patients and early diagnosis are necessary to improve survival.     

颈椎终板弧形高度与椎间隙后缘骨赘的相关性研究

目的：通过对颈椎病患者上下终板弧形高度、椎间隙高度与椎间隙后骨赘的影像学测量，研究其相关性及其临床应用价值。方法：收集2017年9月至2018年9月颈椎病手术108例患者的临床资料，男48例，年龄30~72岁，平均52岁，女60例，年龄37~79岁，平均54岁。其中C_2，3 6例，C_3，4 15例，C_4，5 32例，C_5，6 42例，C_6，7 13例。术前及术后摄颈椎X线片，利用PACS（Picture Archiving and Communication Systems）调阅影像，测量椎间隙的下上终板弧形高度（L₁，L₂），椎间隙高度（L₃）及后方骨赘的宽度（L₄）。利用Spearman分析它们之间的相关性。结果：L₁与L₄对比（r=-0.34，P<0.05），L₃与L₄对比（r=-0.36，P<0.05），存在负相关。L₁与L₃对比（r=0.38，P<0.05），L₂与L₃对比（r=0.48，P<0.05），存在正相关。L₁与L₂对比（P>0.05），L₂与L₄对比（P>0.05），差异无统计学意义。结论：下终板弧形高度与椎间隙后缘骨赘宽度呈负相关，通过其测量可明确颈椎退变程度，对颈椎病的早期防治有指导意义。     

耳穴贴压联合涌泉穴按摩对老年原发性高血压患者血压变异性的影响

目的:探讨耳穴贴压联合涌泉穴按摩治疗老年原发性高血压的效果及对患者血压变异性(BPV)的影响。方法:将94例老年原发性高血压患者随机分为对照组(n=47)和观察组(n=47)。常规西医治疗基础上,观察组给予王不留行籽耳穴贴压联合涌泉穴按摩治疗。比较两组治疗前后收缩压(SBP)、舒张压(DBP)水平、SBP/DBP下降幅度并评估降压疗效,BPV根据24 h动态血压监测结果评估,计算两组治疗前后24h SBP标准差(24h SBP)、24h DBP标准差(24h DBP)、白天SBP标准差(dSSD)、白天DBP标准差(dDSD)、夜间SBP标准差(nSSD)和夜间DBP标准差(nDSD),记录两组治疗期间不良反应情况。结果:观察组治疗后SBP、DBP水平和下降幅度均优于对照组(P<0.05); 观察组降压总有效率97.87%明显高于对照组82.98%,差异有统计学意义(P<0.05); 对照组治疗后24h SBP、24h DSD、dSSD、dDSD较治疗前有明显下降(P<0.05),观察组治疗后24h SBP、24h DSD、dSSD、dDSD、nSSD显著低于治疗前(P<0.05),观察组治疗后24h SBP、24h DSD、dSSD均显著低于对照组,差异有统计学意义(P<0.05); 两组不良反应以头晕、头痛、恶心和眩晕为主,症状程度均较轻,患者耐受性好,组间不良反应率比较差异均无统计学意义(P<0.05)。结论:常规西医治疗基础上给予中医耳穴贴压联合涌泉穴按摩,不仅能有效降低老年原发性高血压患者血压水平和增益降压疗效,而且能显著降低BPV。