Targeting immune dysfunction in aging

Human aging is a multifactorial phenomenon that affects numerous organ systems and cellular processes, with the immune system being one of the most dysregulated. Immunosenescence, the gradual deterioration of the immune system, and inflammaging, a chronic inflammatory state that persists in the elderly, are among the plethora of immune changes that occur during aging. Almost all populations of immune cells change with age in terms of numbers and/or activity. These alterations are in general highly detrimental, resulting in an increased susceptibility to infections, reduced healing abilities, and altered homeostasis that promote the emergence of age-associated diseases such as cancer, diabetes, and other diseases associated with inflammation. Thanks to recent developments, several strategies have been proposed to target central immunological processes or specific immune subpopulations affected by aging. These therapeutic approaches could soon be applied in the clinic to slow down or even reverse specific age-induced immune changes in order to rejuvenate the immune system and prevent or reduce the impact of various diseases. Due to its systemic nature and interconnection with all the other systems in the body, the immune system is an attractive target for aging intervention because relatively targeted modifications to a small set of cells have the potential to improve the health of multiple organ systems. Therefore, anti-aging immune targeting therapies could represent a potent approach for improving healthspan. Here, we review aging changes in the major components of the immune system, we summarize the current immune-targeting therapeutic approaches in the context of aging and discuss the future directions in the field of immune rejuvenation.     

M-MDSC在非霍奇金淋巴瘤中表达及临床意义

目的 探讨单核细胞型髓系来源抑制性细胞(M-MDSC)在非霍奇金淋巴瘤(NHL)患者中的表达水平以及临床意义.方法 选取2017年9月至2020年1月解放军第九○一医院和安徽医科大学第二附属医院35例初诊NHL患者作为试验组,同期选取20例健康志愿者作为对照组.比较两组研究对象M-MDSC、精氨酸酶-1(Arg-1)mRNA及诱导型一氧化氮合酶(iN-OS)mRNA的表达水平.分析M-MDSC与NHL患者年龄、性别、临床分期、病理分型、乳酸脱氢酶(LDH)以及IPI评分等临床指标的相关性.结果 试验组患者M-MDSC表达水平为(32.64±11.23)％,高于对照组,差异有统计学意义(P<0.05).Ⅲ～Ⅳ期、LDH升高及IPI评分为3～5分的NHL患者,M-MDSC水平升高,差异有统计学意义(P<0.05).试验组患者Arg-1水平为(18.12±5.25)ng/mL,iNOS mRNA相对水平为(12.36±3.68),均高于对照组,差异有统计学意义(P<0.05).结论 M-MDSC参与NHL患者发病过程,与疾病进展密切相关,可能成为治疗NHL的新靶点.     

胃癌患者免疫功能及炎症水平的变化与腹腔镜术后发生医院感染的关系

目的探讨胃癌患者免疫功能及炎症水平的变化与腹腔镜手术后发生医院感染的关系。方法选取腹腔镜手术治疗胃癌并发术后感染患者70例,同期未感染患者70例。检测感染患者血清中免疫细胞及炎症相关因子水平变化情况。结果感染组患者血清中CD3+、CD4+、CD8+、CD4+/CD8+水平明显低于未感染组(P<0.05);感染组患者血清中CRP和IL-6水平明显高于未感染组(P<0.05)。同时对感染组患者进行分析发现,感染率随CD4+水平下降呈显著上升趋势(P<0.05)。ROC分析显示:血清CRP、IL-6及CD4+对腹腔镜手术治疗胃癌后发生医院感染具有较高的预测诊断价值,ROC-AUC均在0.72以上,敏感度和特异度均高于0.7。结论胃癌患者免疫功能及炎症因子水平的变化与腹腔镜手术后发生医院感染有密切关系,对手术后发生医院感染有一定的预测诊断价值,因此,术后应密切关注患者免疫功能及炎症水平的变化,降低感染率。     

The optimal timing for the interval to surgery after short course preoperative radiotherapy (5 ×5 Gy) in rectal cancer - are we too eager for surgery?

BackgroundThe improved overall survival (OS) after short course preoperative radiotherapy (SCPRT) using 5 × 5 Gy reported in the early rectal cancer trials could not be replicated in subsequent phase III trials. This original survival advantage is attributed to poor quality of surgery and the large differential in local recurrence rates, with and without SCPRT. Immuno-modulation during and after SCPRT and its clinical implications have been poorly investigated. We propose an alternative explanation for this survival benefit in terms of immunological mechanisms induced by SCPRT and the timing of surgery, which may validate the concept of consolidation chemotherapy.Material and methodsWe reviewed randomized controlled trials (RCTs) and studies of SCPRT from 1985 to 2019. We aimed to examine the precise timing of surgery in days following SCPRT and identify evidence for immune modulation, neo-antigens and memory cell induction by radiation.ResultsConsiderable variability is reported in randomised trials for median overall treatment time (OTT) from start of SCPRT to surgery (8–14 days). Only three early trials showed a benefit in terms of OS from SCPRT, although the level of benefit in preventing local recurrence was consistent across all trials. Different patterns of immune effects are observed within days after SCPRT depending on the OTT, but human leukocyte antigen (HLA)-1 expression was not upregulated.ConclusionsSCPRT has a substantial immune-stimulatory potential. The importance of the timing of surgery after SCPRT may have been underestimated. An optimal interval for surgery after 5 × 5 Gy may lead to better outcomes, which is possibly exploited in total neoadjuvant therapy schedules using consolidation chemotherapy. Individual patient meta-analyses from appropriate SCPRT trials examining outcomes for each day and prospective trials are needed to clarify the validity of this hypothesis. The interaction of SCPRT with tumour adaptive immunology, in particular the kinetics and timing, should be examined further.     

芪参补气胶囊治疗稳定期慢性阻塞性肺疾病肺气虚证的疗效观察

目的：探索芪参补气胶囊治疗稳定期慢性阻塞性肺疾病（COPD）肺气虚证的临床疗效与安全性。方法：选取2017年10月16日至2018年11月20日在新疆维吾尔族自治区克州人民医院呼吸内科门诊随诊的COPD稳定期肺气虚证患者480例作为研究对象，随机分为观察组和对照组，每组240例，进行为期52周的观察。2组患者均给予健康指导、家庭氧疗、沙美特罗替卡松粉吸入剂、竹沥胶囊等基础治疗；对照组在基础治疗上给予玉屏风胶囊口服，2粒/次，3次/d；观察组在基础治疗上给予芪参补气胶囊口服，3粒/次，3次/d。观察比较2组患者的相关指标。结果：观察组平均急性加重次数（1.62±0.93）次，对照组（1.83±0.97）次，观察组发作次数显著减少（t=2.262，P=0.012）。观察组相对于对照组的急性加重风险RR=0.869（0.763~0.988，P=0.032），降低了13.1%。伴有咳嗽、喘息、便秘或吸烟的患者，观察组急性加重风险更低（P<0.05）。观察组CAT评分、FEV1显著优于对照组（P<0.05）。观察组炎性反应指标（TNF-α、IL-6、IL-8）改善情况显著优于对照组。观察组不良事件发生率显著低于对照组。结论：芪参补气胶囊与玉屏风散均具有良好的提高免疫功能，改善COPD属肺气虚证者咳痰喘症状的作用。其中芪参补气胶囊减少急性加重风险的效果较玉屏风胶囊更好，且安全性良好，值得推广使用。     

桂枝芍药知母汤对类风湿性关节炎患者实验室指标和免疫功能的影响

目的:探讨桂枝芍药知母汤对类风湿性关节炎患者实验室指标和免疫功能的影响。方法:选取2014年12月至2016年12月南京中医药大学附属南京市中西医结合医院收治的类风湿关节炎患者110例作为研究对象，按照随机数字表法分为对照组和观察组，每组55例。对照组采用常规西医治疗，观察组在对照组的基础上联合桂枝芍药知母汤治疗，2组均治疗1个月。比较2组临床效果、临床症状改善情况、实验室指标及免疫功能指标水平；统计2组不良反应发生率。结果:观察组总有效率为92.73%，高于对照组（78.18%，P<0.05）。与治疗前比，治疗1个月后，2组握力均增大，且观察组大于对照组（P<0.05）；2组晨僵时间、20 m步行时间均缩短，且观察组短于对照组（P<0.05）；2组关节压痛数、关节肿胀数、ESR、MPV、PDW及血清CRP、血浆IgA、IgG、IgM、RF水平均降低，且观察组低于对照组（P<0.05）；2组血清C3水平均升高，且观察组高于对照组（P<0.05）。治疗期间，观察组不良反应发生率为0.00%，低于对照组（10.91%，P<0.05）。结论:桂枝芍药知母汤治疗类风湿性关节炎，可改善患者实验室指标，增强免疫功能，提高疗效，安全性较高。     

扶正抑癌汤联合腹腔镜辅助小切口根治手术治疗胃癌临床研究

目的:探讨扶正抑癌汤联合腹腔镜辅助小切口根治手术治疗胃癌的效果及对患者免疫功能的影响。方法:选择80例胃癌患者,按随机数字表法分为观察组和对照组各40例。对照组行腹腔镜辅助小切口根治手术治疗,观察组予以扶正抑癌汤联合腹腔镜辅助小切口根治术手术治疗,比较2组患者临床疗效及免疫功能。结果:治疗前,2组中医症状评分比较,差异无统计学意义(P>0.05)。治疗后,2组中医症状评分较治疗前下降(P<0.05),且观察组中医症状评分低于对照组(P<0.05)。治疗前,2组癌胚抗原(CEA)、糖类抗原199 (CA199)、糖类抗原125 (CA125)水平比较,差异无统计学意义(P>0.05)。治疗后,2组CEA、CA199、CA125水平较治疗前下降(P<0.05),且观察组CEA、CA199、CA125水平低于对照组(P<0.05)。治疗前,2组CD4^+、CD8^+、CD4^+/CD8^+水平比较,差异无统计学意义(P>0.05)。治疗后,2组CD4^+、CD8^+、CD4^+/CD8^+水平较治疗前升高(P<0.05),且观察组CD4^+、CD8^+、CD4^+/CD8^+水平高于对照组(P<0.05)。结论:扶正抑癌汤联合腹腔镜辅助小切口根治手术治疗胃癌效果显著,可有效降低相关肿瘤标志物水平,并改善患者免疫功能。     

肾炎1号方联合西药治疗肾病综合征疗效及对患者凝血指标、免疫功能的影响

目的:探讨肾炎1号方联合西药治疗肾病综合征临床疗效及对患者凝血指标、免疫功能的影响。方法:选取肾病综合征患者共52例,分为对照组26例、治疗组26例。两组患者均予以基础治疗,对照组在基础治疗上给予泼尼松片治疗。治疗组在对照组基础上加用肾炎1号方治疗。结果:与对照组治疗后相比,治疗组治疗24 h后Upr、CHOL、TG、Scr、Fg、D-D均下降,差异有统计学意义(P<0.05)。治疗组治疗后补体C₃升高明显,与对照组比较,差异有统计学意义(P<0.05)。治疗后治疗组中医证候积分各项均低于对照组,治疗组总有效率88.46%高于对照组的76.92%,差异均有统计学意义(P<0.05)。结论:肾炎1号方联合西药治疗肾病综合征临床效果较好,能更有效地控制患者蛋白尿、升高血清白蛋白水平、降低血清胆固醇,并且能调节机体体液免疫紊乱、改善高凝状态。     

活血清胰汤灌肠辅助手术治疗对急性重症胰腺炎患者的疗效观察

目的：探讨活血清胰汤灌肠辅助手术治疗急性重症胰腺炎对患者AMS、UAMY、LPS水平及免疫功能的影响。方法：选取2019年3月至2020年3月陕西省宝鸡市中医医院收治的急性重症胰腺炎患者70例作为研究对象，按随机数字表法将其分为对照组和观察组，每组35例。2组均采用经内镜逆行性胰胆管造影术进行治疗，对照组术后给予常规治疗，观察组术后在对照组的基础上加用活血清胰汤灌肠治疗，2组均治疗1周。比较2组治疗1周后的临床疗效；比较2组治疗前、治疗1周后的胰腺炎标志物水平、细胞免疫指标及体液免疫指标水平。结果：治疗1周后，观察组总有效率为94.29%，高于对照组（77.14%，P<0.05）。与治疗前比较，治疗1周后，2组血清AMS、LPS、UAMY及CD8+水平均降低，且观察组低于对照组（P<0.05）；2组血清CD3+、CD4+、IgG、IgM、IgA水平及CD4+/CD8+比值均升高，且观察组高于对照组（P<0.05）。结论：活血清胰汤灌肠辅助手术治疗急性重症胰腺炎，可通过降低患者血清AMS、LPS及UAMY水平，缓解炎性反应，同时可改善免疫功能，进而有助于提高疗效。