Postoperative development of sarcopenia is a strong predictor of a poor prognosis in patients with adenocarcinoma of the esophagogastric junction and upper gastric cancer

Background

There were few studies assessed the postoperative sarcopenia in patients with cancers. The objective of present study was to assess whether postoperative development of sarcopenia could predict a poor prognosis in patients with adenocarcinoma of esophagogastric junction, (AEG) and upper gastric cancer (UGC).

LncRNA PCED1B-AS1调控NLRP3促进巨噬细胞清除结核分枝杆菌的机制研究

目的　研究长链非编码RNA PCED1B-AS1调控核苷酸结合寡聚化结构域样受体3（NLR family pyrindomain containing 3, NLRP3）对巨噬细胞清除结核分枝杆菌和分泌炎症因子的影响。方法　在巨噬细胞RAW264.7中转染pcDNA-PCED1B-AS1,并用结核分枝杆菌感染,qRT-PCR方法检测PCED1B-AS1和TNF-α、IL-6 mRNA水平,用菌落形成实验检测巨噬细胞对结核分枝杆菌的清除作用,Western blot方法检测细胞中NLRP3蛋白表达水平。将NLRP3 小干扰RNA（small interfering RNA, siRNA）和pcDNA-PCED1B-AS1共转染到巨噬细胞中,用结核分枝杆菌感染,同样检测细胞中TNF-α、IL-6 mRNA水平和菌落量。结果　结核分枝杆菌感染后的巨噬细胞中PCED1B-AS1水平降低,TNF-α、IL-6 mRNA水平升高。转染pcDNA-PCED1B-AS1后的巨噬细胞经过结核分枝杆菌感染以后,细胞中PCED1B-AS1、TNF-α、IL-6 mRNA水平升高,形成的菌落量减少,细胞中NLRP3蛋白表达水平升高。NLRP3 siRNA可以逆转过表达PCED1B-AS1对结核分枝杆菌感染的巨噬细胞中TNF-α、IL-6 mRNA表达和菌落量形成的影响。结论　上调PCED1B-AS1促进巨噬细胞清除结核分枝杆菌,诱导细胞表达TNF-α、IL-6 mRNA的机制与上调NLRP3表达有关。     

凝血功能改变与COVID-19后发生急性缺血性脑卒中相关

[摘要]　目的　比较感染与未感染2019新型冠状病毒的急性缺血性脑卒中患者的临床特点、炎症指标及凝血功能,探讨新型冠状病毒病（COVID-19）后发生急性缺血性脑卒中的作用。方法　采用单中心回顾性研究设计,纳入2022年11月5日至2023年2月5日于我院治疗且完善2019新型冠状病毒核酸检测的急性缺血性脑卒中患者187例,其中合并COVID-19患者75例（COVID-19组）、未发生COVID-19患者112例（无COVID-19组）。分析两组患者的一般临床资料、炎症和凝血功能指标,包括中性粒细胞/淋巴细胞比值（NLR）、D-二聚体、纤维蛋白原（FIB）等。构建多因素logistic回归方程,分析COVID-19后发生急性缺血性脑卒中的独立危险因素。结果　COVID-19组的NLR[3.62（2.31,6.71） vs 2.64（1.87,5.04）,P=0.014]、D-二聚体[0.70（0.32,2.27）mg/L vs 0.37（0.27,0.76）mg/L,P=0.001]、FIB[4.21（3.26,5.17）g/L vs 3.25（2.77,3.87）g/L,P<0.001]和淋巴细胞计数[1.40（1.03,1.71）×109/L vs 1.61（1.09,2.21）×109/L,P<0.05]高于无COVID-19组。多因素logistic回归分析结果表明,既往脑卒中史（OR =15.430,95% CI=(1.538,19.175),P= 0.009)、D-二聚体（OR =1.425,95% CI=(1.104,1.840),P= 0.007）及FIB（OR =2.405,95% CI=(1.683,3.437),P= 0.001）是COVID-19后发生急性缺血性脑卒中的独立危险因素。结论　感染COVID-19后急性缺血性卒中患者的炎症和凝血的血清生物标志物升高,COVID-19后缺血性脑卒中的发病与高凝状态相关。     

预测非肌层浸润性膀胱尿路上皮癌患者复发的炎症反应标志物评分系统构建

目的探讨采用4种炎症反应标志物构建预测非肌层浸润性膀胱尿路上皮癌(NMIBC)患者复发的炎症评分系统。方法选取海南医学院第一附属医院在2012-01-01-2016-02-27收治的271例NMIBC患者。术前1周收集患者中性粒细胞与淋巴细胞比值(NLR)、血小板与淋巴细胞比值(PLR)、白蛋白与球蛋白比值(AGR)、淋巴细胞与单核细胞比值(LMR)。基于NLR、PLR、AGR和LMR最佳截断值构建中性粒细胞与淋巴细胞比值-血小板和淋巴细胞比值-白蛋白球蛋白比值-淋巴细胞和单核细胞比值(NPAL)评分系统(NPALSS),并结合多因素Cox风险比例模型分析NPALSS的临床价值。结果所有患者均获得随访,随访时间18~89个月,平均时间为(55.84±22.68)个月。随访末期64例患者复发,复发率为23.6%,中位无复发生存时间41个月。NLR、PLR、AGR和LMR 4种炎症反应标志物的曲线下面积(AUC)分别为0.785、0.694、0.866和0.750,最佳截断值分别为2.37、136、1.71和3.64。NLR≤2.37、PLR<136、AGR≥1.71、LMR≤3.64患者的无复发生存率高于NLR>2.37、PLR≥136、AGR<1.71、LMR>3.64患者,均Log-rank P<0.001。NPALSS不同等级的生存曲线比较差异有统计学意义,均Log-rank P<0.001。肿瘤数量(HR多发=1.026,95%CI为1.002~1.051)、T分期(HRT1=1.031,95%CI为1.009~1.054)、NPALSS(HR_1级=1.017,95%CI为1.001~1.034;HR_2级=1.935,95%CI为1.438~2.605;HR_3级=2.213,95%CI为1.646~2.977;HR_4级=2.518,95%CI为1.810~3.503)是NMIBC患者复发的独立危险因素,均P<0.05。结论结合NLR、PLR、AGR和LMR最佳截断值所构建的NPALSS可以有效预测高复发风险的NMIBC患者。     

术前NLR和PLR对上皮性卵巢癌患者预后的评估价值

目的:探讨术前中性粒细胞与淋巴细胞比值(NLR)和血小板与淋巴细胞比值(PLR)对上皮性卵巢癌患者预后的评估价值。方法:收集2005年11月至2012年12月在天津市中心妇产科医院初治且经手术治疗的153例卵巢良性肿瘤和206例上皮性卵巢癌患者的临床病理资料,比较术前NLR和PLR在卵巢良恶性肿瘤的区别,根据统计学方法选取NLR和PLR临界值,分析NLR和PLR与上皮性卵巢癌临床病理因素的关系。通过单因素及多因素分析评估术前NLR和PLR对患者术后生存的影响。结果:术前NLR和PLR水平在上皮性卵巢癌中明显高于卵巢良性肿瘤。选取NLR=2.62和PLR=173分别作为临界值。单因素分析结果显示,FIGO分期晚、中-低分化、腹水、脉管癌栓、CA125≥35、NLR≥2.62、PLR≥173是影响患者术后无病生存期(DFS)的危险因素(P0.05);FIGO分期晚、腹水、脉管癌栓、CA125≥35、PLR≥173是影响患者术后总生存期(OS)的危险因素(P0.05)。多因素分析显示,FIGO分期晚、NLR≥2.62、脉管癌栓是上皮性卵巢癌患者DFS的独立危险因素(P0.05)。结论:NLR和PLR方便测得且价格便宜,对卵巢癌的预后有一定的评估价值。     

IL-1 receptor-associated kinase 1 participates in the modulation of the NLRP3 inflammasome by tumor-associated macrophages in hepatocellular carcinoma

BackgroundHepatocellular carcinomas (HCCs) occur frequently in the digestive system and are associated with high mortality. This current study examined the regulatory relationship between interleukin (IL)-1 receptor-associated kinase 1 (IRAK1), NLR family pyrin domain-containing 3 (NLRP3) inflammasomes, and tumor-associated macrophages (TAMs) in the growth and metastasis of HCC.MethodsThe expression of IRAK1 and NLRP3 was assessed in tissues and cells via quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Immunohistology was performed to detect the macrophage markers CD68, CD163, and CD168 in tumor tissues. Small interfering (si)RNA targeting IRAK1 (si-IRAK1) was designed to silence IRAK1 expression. Following si-IRAK1 transfection and/or co-culture with TAMs, HCC cell viability, proliferation, migration, and invasion, as well as the expression of NLRP3 and pro-inflammatory cytokines IL-1 β, IL-18, and monocyte chemotactic protein 1 (MCP-1) were assessed.ResultsHCC tissues showed elevated expression of IRAK1 and NLRP3, as well as increased expression of the macrophage markers CD68, CD163, and CD168, compared to adjacent healthy tissues. Silencing of IRAK1 expression in HepG2 and Huh7 cells resulted in suppression of cell proliferation, migration, and invasion, and also reduced expression of NLRP3 and the pro-inflammatory cytokines IL-1β, IL-18, and MCP-1. Moreover, TAMs promoted HepG2 and Huh7 cell proliferation, migration, and invasion, and elevated the expression of NLRP3, IL-1β, IL-18, and MCP-1. Furthermore, IRAK1 silencing reversed the effects of TAMs on HepG2 and Huh7 cells.ConclusionsThe expression of IRAK1 was associated with HCC growth and metastasis, as well as NLRP3 inflammasome activation. The ability of TAMs to promote HCC growth and metastasis may be activated by NLRP3 inflammasomes and regulated by IRAK1.     

术前血清CA125、HE4和中性粒细胞与淋巴细胞比值联合检测在子宫内膜癌诊断中的作用

目的:探讨血清糖类抗原125（carbohydrate antigen 125,CA125）、人附睾蛋白4（human epididymis protein 4,HE4）、中性粒细胞与淋巴细胞比值（neutrophil-lymphocyte ratio,NLR）联合检测在子宫内膜癌诊断中的作用。方法:选取42例子宫内膜癌患者、50例子宫内膜良性疾病患者和50例健康体检人群。采用SYSMEX XN550全自动血液分析仪计数术前外周血中性粒细胞和淋巴细胞,计算NLR;采用Maglumi4000全自动化学发光仪检测术前血清CA125、HE4水平。采用ROC曲线分析CA125、HE4、NLR和三者联合指标在诊断子宫内膜癌中的作用。结果:外周血NLR在健康组、良性组和子宫内膜癌组中逐渐增高,且差异有统计学意义（P<0.05）;子宫内膜癌组HE4表达量显著高于良性组与健康组（P<0.05）,而良性组与健康组之间差异无统计学意义（P>0.05）;CA125表达量在三组中差异无统计学意义（P>0.05）。CA125、HE4、NLR及三者联合标记物的AUC分别为0.530、0.733、0.795、0.823,当分别取它们的临界值时,特异性分别为70.8%、85.1%、61.7%、83.0%,敏感性分别为40.0%、63.3%、86.7%、73.3%。单项指标NLR的敏感性最高,HE4的特异性最高,联合指标的特异性和敏感性都很高。结论:术前血清CA125、HE4和NLR联合检测具有较高的特异性和敏感性,联合检测可以互为补充,提高子宫内膜癌的诊断准确率,对子宫内膜癌的诊断具有指导意义。     

非小细胞肺癌免疫治疗前后N LR和PLR变化及对免疫治疗疗效的预测价值

目的:探讨中性粒细胞/淋巴细胞比值(neutrophil to lymphocyte ratio,NLR)和血小板/淋巴细胞比值(platelet to lymphocyte ratio,PLR)及其动态变化对非小细胞肺癌(non-small cell lung cancer,NSCLC)免疫治疗疗效和预后的影响.方法...     

Targeting whole body metabolism and mitochondrial bioenergetics in the drug development for Alzheimer's disease

Aging is by far the most prominent risk factor for Alzheimer's disease (AD), and both aging and AD are associated with apparent metabolic alterations. As developing effective therapeutic interventions to treat AD is clearly in urgent need, the impact of modulating whole-body and intracellular metabolism in preclinical models and in human patients, on disease pathogenesis, have been explored. There is also an increasing awareness of differential risk and potential targeting strategies related to biological sex, microbiome, and circadian regulation. As a major part of intracellular metabolism, mitochondrial bioenergetics, mitochondrial quality-control mechanisms, and mitochondria-linked inflammatory responses have been considered for AD therapeutic interventions. This review summarizes and highlights these efforts.