抗PD-1/PD-L1免疫检查点抑制剂的皮肤免疫相关不良反应的研究进展

随着免疫检查点抑制剂（immune checkpoint inhibitors，ICPI）在国内外临床试验和应用中的逐步推广，越来越多的患者从免疫治疗中获得显著的疗效。其中抗程序细胞死亡蛋白1（programmed death-1，PD-1）及其配体（PD-1 ligand，PD-L1）免疫检查点抑制剂已被美国食品药品管理局（FDA）批准用于恶性黑色素瘤、转移性鳞状非小细胞肺癌、晚期肾癌、头颈鳞状细胞癌、尿路上皮癌等肿瘤的治疗。但PD-1/PD-L1单抗也会引起免疫相关性皮肤、消化道、肝脏、内分泌、肺部等器官的不良反应，皮肤毒性如皮疹、白癜风、皮肤干燥症等是最常见也是最早发生的不良反应。     

Role of macrophages in peripheral nerve injury and repair

Resident and inflammatory macrophages are essential effectors of the innate immune system. These cells provide innate immune defenses and regulate tissue and organ homeostasis. In addition to their roles in diseases such as cancer, obesity and osteoarthritis, they play vital roles in tissue repair and disease rehabilitation. Macrophages and other inflammatory cells are recruited to tissue injury sites where they promote changes in the microenvironment. Among the inflammatory cell types, only macrophages have both pro-inflammatory(M1) and anti-inflammatory(M2) actions, and M2 macrophages have four subtypes. The co-action of M1 and M2 subtypes can create a favorable microenvironment, releasing cytokines for damaged tissue repair. In this review, we discuss the activation of macrophages and their roles in severe peripheral nerve injury. We also describe the therapeutic potential of macrophages in nerve tissue engineering treatment and highlight approaches for enhancing M2 cell-mediated nerve repair and regeneration.     

食管癌根治性放疗剂量研究进展

同步放化疗是不可手术局部晚期食管癌的标准治疗模式,国际推荐根治性放疗剂量为50.0~50.4Gy,但中国食管癌与西方国家在病理类型、生物学行为等方面大有不同,行根治性放疗剂量仍倾向于60Gy。增加放疗剂量能否带来生存获益成为临床亟待解决的问题。有研究认为高剂量放疗可提高局控率、改善生存,但也有研究认为提高剂量未能带来生存获益,且可增加不良反应事件发生率。因此,本文就食管癌根治性放疗剂量对预后的影响进行探讨,并通过放化疗后疗效评估对放疗剂量做出适当调整,以期达个体化放疗。     

农村青少年不同时期家庭逆境与精神病理症状的关联

目的探讨家庭逆境致精神病理症状结局的累积性与关键期效应,为预防与干预逆境伤害提供依据。方法2017年12月,采用方便抽样的方法选取安徽省阜阳地区2所农村学校的710名青少年。采用《童年期不良经历问卷》评估家庭逆境,《MacArthur健康与行为问卷》评价内化症状和外化症状。采用多元线性回归分析家庭逆境发生时间与数量和精神病理症状的关联。结果持续家庭逆境组与内化症状、外化症状增加均有相关性[β值(95%CI)分别为0.35(0.15~0.54),0.16(0.01~0.32)]。家庭逆境数量为2和≥3与内化症状[β值(95%CI)分别为0.20(0.04~0.36),0.42(0.24~0.60)]、外化症状[β值(95%CI)分别为0.14(0.01~0.26),0.23(0.09~0.37)]增加有关。在仅童年期家庭逆境中,家庭逆境数量为2和≥3的内化症状[β值(95%CI)分别为0.23(0.06~0.41),0.34(0.11~0.58)]、外化症状[β值(95%CI)分别为0.17(0.02~0.31),0.21(0.02~0.39)]的风险增高。在持续家庭逆境组中,逆境数量≥3与内化症状、外化症状相关[(β值(95%CI)分别为0.56(0.31~0.82),0.24(0.02~0.45)]。仅青春期家庭逆境与精神病理症状无关。结论家庭逆境的多次发生可增加精神病理症状风险,童年期可能是家庭逆境致精神病理症状的关键期。     

临床实习生对患者隐私的认知及保护情况调查

目的了解临床实习生对患者隐私的认知以及在临床实践中对患者隐私的保护情况,探讨患者隐私教育及临床实习中存在的问题,分析成因并提出加强患者隐私教育、引导实习生合理获取患者隐私的具体建议,以改善临床医学教育过程中存在的薄弱环节。方法随机选取海军军医大学等5所医学院校的572名临床医学实习生为调查对象,发放调查问卷。主要内容包括实习生隐私教育评分、对于隐私保护法及隐私具体范围的知晓情况、临床实践中是否泄露隐私、隐私与临床诊疗等方面,调查结果采用SPSS 21.0软件进行分析。结果27.6%实习生曾发生过泄露患者隐私的情况,58.9%实习生不了解隐私相关法律法规及隐私具体范围,95.4%实习生认为出于诊疗目的而获取患者隐私信息很有必要,但仍有56.6%实习生曾回避涉及患者隐私的医疗活动。结论临床医学实习生的教育中患者隐私教育相对欠缺并有待进一步加强。实习生应当自觉保护患者隐私,维护患者利益,并树立对于患者隐私的合理认知,从患者隐私中提取有价值的信息。     

益气化瘀解毒方对MRP、GST-π和Topo Ⅱ基因在Sorafenib获得性耐药人肝癌QGY7702细胞表达的干预研究

目的探讨益气化瘀解毒方干预后对Sorafenib获得性耐药人肝癌QGY7702细胞(QGY7702/Sora)增殖及MRP、GST-π和Topo Ⅱ基因表达的影响。方法培养QGY7702/Sora细胞和QGY7702细胞,利用Cell Counting Kit-8(CCK-8)法检测Sorafenib对细胞的半数抑制率浓度(IC50值),计算耐药指数RI;观察益气化瘀解毒方对耐药细胞的增殖影响;采用荧光定量PCR检测药物干预前后2种细胞中MRP、GST-π和Topo Ⅱ基因表达水平。结果亲本细胞和耐药细胞Sorafenib的IC50值分别为(7.993±0.522)μmol/L和(19.651±1.216)μmol/L,RI约为2.5。益气化瘀解毒方可抑制耐药细胞的增殖活性。2种细胞的MRP、GST-π、Topo Ⅱ表达量无明显差异(P>0.05)。Sorafenib组可促进耐药细胞MRP 、GST-π基因的过表达(P<0.05),益气化瘀解毒方组可抑制GST-π基因的过表达(P<0.01),且联合Sorafenib可显著提高Topo Ⅱ基因的表达量(P<0.01)。结论 QGY7702/Sora细胞MRP、GST-π和Topo Ⅱ的表达水平与亲本细胞无显著差异。耐药细胞对Sorafenib敏感性降低与MRP、GST-π过表达相关,而益气化瘀解毒方拮抗Sorafenib耐药与抑制GST-π过表达相关。     

Analysis of early mortality and related risk factors in maintenance hemodialysis patients

Objective To analyze the early mortality and related risk factors of new hemodialysis patients in Zhejiang province, and provide basis for reducing the death risk of hemodialysis patients. Methods The early mortality and related factors of new hemodialysis patients from January 1, 2010 to June 30, 2018 were retrospectively analyzed using the database of Zhejiang province hemodialysis registration. The early mortality was defined as death within 90 days of dialysis. Cox regression model was used to analyze the related risk factors of the early mortality in hemodialysis patients. Results The mortality was the highest in the first month after dialysis (46.40/100 person year), and gradually stabilized after three months. The early mortality was 25.33/100 person year. The mortality within 120 days and 360 days were 21.40/100 person year and 11.37/100 person year, respectively. The elderly (≥65 years old, HR=1.981, 95%CI 1.319-2.977, P＜0.001), primary tumor (HR=3.308, 95%CI 1.137-5.624, P=0.028), combined with tumors (not including the primary tumor, HR=2.327, 95%CI 1.200-4.513, P=0.012), temporary catheter (the initial dialysis pathway, HR=3.632, 95%CI 1.806-7.307, P＜0.001), lower albumin (＜30 g/L, HR=2.181, 95%CI 1.459-3.260, P＜0.001), lower hemoglobin (every 0.01 g/L increase, HR=0.861, 95%CI 0.793-0.935, P=0.001), lower high density lipoprotein (＜0.7 mmol/L, HR=1.796, 95%CI 1.068-3.019, P=0.027) and higher C reactive protein (≥40 mg/L, HR=1.889, 95%CI 1.185-3.012, P=0.008) were the risk factors of early death for hemodialysis patients. Conclusions The early mortality of hemodialysis patients is high after dialysis, and gradually stable after 3 months. The elderly, primary tumor, combined with tumors, the initial dialysis pathway, lower albumin, lower hemoglobin, lower high density lipoprotein and higher C reactive protein are the risk factors of early death for hemodialysis patients.