程序性死亡受体1和程序性死亡受体配体1在非小细胞肺癌组织中的表达情况及临床意义

目的探讨程序性死亡受体1(PD-1)和程序性死亡受体配体1(PD-L1)在非小细胞肺癌(NSCLC)组织中的表达情况及临床意义。方法选择150例NSCLC患者的NSCLC组织及其癌旁组织,采用实时荧光定量聚合酶链反应(PCR)检测两种组织中PD-1 mRNA和PD-L1 mRNA的相对表达量。采用免疫组织化学染色法检测NSCLC组织中PD-1和PD-L1的表达情况,分析PD-1和PD-L1表达情况与患者临床特征的关系。采用流式细胞术检测NSCLC组织和癌旁组织中CD4^+-PD-1、CD8^+-PD-1、CD14^+-PD-L1、CD68^+-PD-L1的表达水平。结果NSCLC组织中PD-1 mRNA和PD-L1 mRNA的相对表达量分别为(5.03±1.92)和(4.95±1.09),分别高于癌旁组织的(1.72±0.81)和(1.25±0.24),差异均有统计学意义(P﹤0.05)。TNM分期为Ⅲ~Ⅳ期、低分化、有淋巴结转移、有远处转移的NSCLC患者NSCLC组织中PD-1和PD-L1的高表达率均明显高于TNM分期为Ⅰ~Ⅱ期、高+中分化、无淋巴结转移、无远处转移的患者,差异均有统计学意义(P﹤0.01)。NSCLC组织中CD4^+-PD-1、CD8^+-PD-1、CD14^+-PD-L1、CD68^+-PD-L1的表达水平均明显高于癌旁组织,差异均有统计学意义(P﹤0.01)。结论PD-1和PD-L1在NSCLC组织中高表达,可能成为一种新的生物标志物,PD-1/PD-L1信号通路可能参与了NSCLC的免疫逃逸过程,对其逃逸机制进行研究可以为NSCLC患者的临床治疗提供新靶点。     

Photoacoustic treatment mitigates cognitive dysfunction in a model of sleep-wake rhythm disturbance

Sleep-wake rhythm disturbances,which are characterized by abnormal sleep timing or duration,are associated with cognitive dysfunction.Photoacoustic treatments including light and sound stimulation have been found to be effective in modulating sleep patterns and improving cognitive behavior in abnormal sleep-wake pattern experiments.In this study,we examined whether light and sound interventions could reduce sleep-wake pattern disturbances and memory deficits in a sleep rhythm disturbance model.We established a model of sleep rhythm disturbance in C57 BL/6 J mice via a sleep deprivation method involving manual cage tapping,cage jostling,and nest disturbance.We used a Mini Mitter radio transmitter device to monitor motor activity in the mice and fear conditioning tests to assess cognitive function.Our results indicated that an intervention in which the mice were exposed to blue light(40-Hz flickering frequency)for 1 hour during their subjective daytime significantly improved the 24-hour-acrophase shift and reduced the degree of memory deficit induced by sleep deprivation.However,interventions in which the mice were exposed to a 40-Hz blue light at offset time or subjective night time points,as well as 2 Hz-blue light at 3 intervention time points(subjective day time,subjective night time,and offset time points),had no positive effects on circadian rhythm shift or memory deficits.Additionally,a 2000-Hz sound intervention during subjective day time attenuated the24-hour-acrophase shift and memory decline,while 440-Hz and 4000-Hz sounds had no effect on circadian rhythms.Overall,these results demonstrate that photoacoustic treatment effectively corrected abnormal sleep-wake patterns and cognitive dysfunction associated with sleep-deprivation-induced disturbances in sleep-wake rhythm.All animal experiments were approved by the Experimental Animal Ethics Committee of Drum Tower Hospital Affiliated to the Medical College of Nanjing University,China(approval No.20171102)on November20,2017.     

Prospective observation: Clinical utility of plasma Epstein–Barr virus DNA load in EBV-associated gastric carcinoma patients

Epstein–Barr virus (EBV)-associated gastric carcinomas (EBVaGCs) may account for 8–9% of all gastric cancer (GC) patients. All previous reports on EBVaGC were retrospective. Prospective study is warranted to evaluate the exact role of EBV status in predicting the prognosis of GC. It is of special interest to figure out whether dynamic detection of plasma EBV-DNA load could be a feasible biomarker for the monitor of EBVaGC. From October 2014 to September 2017, we consecutively collected GC patients (n = 2,760) from Sun Yat-sen University Cancer Center for EBER examination. We detected EBV-DNA load in plasma and tissue samples of EBVaGC patients at baseline. Subsequently, plasma EBV-DNA load was dynamically monitored in EBVaGC patients. The overall prevalence of EBVaGC is 5.1% (140/2,760). The incidence rate of EBVaGC decreased with advanced AJCC 7th TNM stage (p < 0.001), with the corresponding percentages of 9.3, 9.9, 6.7 and 1.4% for Stage I, II, III and IV patients. EBVaGC patients were predominately young males with better histologic differentiation and earlier TNM stage than EBV-negative GC (EBVnGC) patients. EBVaGC patients were confirmed to had a favorable 3-year survival rate (EBVaGC vs. EBVnGC: 76.8% vs. 58.2%, p = 0.0001). Though only 52.1% (73/140) EBVaGC patients gained detectable EBV-DNA and 43.6% (61/140) reached a positive cutoff of 100 copies/ml, we found the plasma EBV-DNA load in EBVaGC decreased when patients got response, while it increased when disease progressed. Our results suggested that plasma EBV-DNA is a good marker in predicting recurrence and chemotherapy response for EBVaGC patients.