Virtual Crossmatching in Kidney Transplantation: The Wait Is Over

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新型冠状病毒肺炎疫情下死亡病例报告分析的现状、思考与建议

医生在日常临床工作中,死亡病例讨论是必不可少的工作内容之一,而在突发公共卫生事件中,对死亡病例的报告与分析则有更深远的意义。新型冠状病毒肺炎疫情为我国带来巨大损失,医疗系统承受巨大压力,而战胜疫情的有利武器便是医疗数据及相关科学研究,死亡病例的系统分析与高效利用是关键一步。该文基于疫情下死亡病例报告记录不完善、人文视角与患者报告缺乏等现状,针对各部门机构面临巨大的数据管理压力,相关制度有待完善,规范化报告和临床科研一体化工作尚不成熟等问题提出方法学思考与建议:①建立国家医药健康数据中心,完善相关法律法规;②加大医药数据管理投入,疫情期间尽早开始数据收集与分析;③完善死亡病例报告相关内容,促进规范化报告形成;④重视死亡病例报告,回顾总结分析,强调疫情过后继续建立并完善相关平台与方案,开展相关科学研究,提升健康卫生数据管理效率,提高医疗系统抗风险能力,促进健康中国战略稳步前进。     

Programmed Cell Death Ligand 1 Expression in Untreated EGFR Mutated Advanced NSCLC and Response to Osimertinib Versus Comparator in FLAURA

IntroductionEGFR mutated (EGFRm) NSCLC tumors occasionally express programmed cell death ligand 1 (PD-L1), although frequency and clinical relevance are not fully characterized. We report PD-L1 expression in patients with EGFRm advanced NSCLC and association with clinical outcomes following treatment with osimertinib or comparator EGFR tyrosine kinase inhibitors in the FLAURA trial (phase III, NCT02296125).MethodsOf 231 tissue blocks available from the screened population (including EGFRm-positive and -negative samples), 197 had sufficient tissue for PD-L1 testing using the SP263 (Ventana, Tucson, Arizona) immunohistochemical assay. Tumor cell (TC) staining thresholds of PD-L1 TC greater than or equal to 1%, TC greater than or equal to 25%, and TC greater than or equal to 50% were applied. Progression-free survival (PFS) was investigator-assessed, per Response Evaluation Criteria in Solid Tumor, version 1.1, according to PD-L1 expressors (TC ≥ 1%) or negatives (TC < 1%) in randomized patients.ResultsPD-L1 staining was successful in 193 of 197 patient formalin-fixed paraffin-embedded blocks; of these, 128 of 193 were EGFRm-positive and 106 of 128 patients were randomized to treatment (osimertinib: 54; comparator: 52). At the PD-L1 TC greater than or equal to 25% threshold, 8% (10 of 128) of EGFRm-positive tumors expressed PD-L1 versus 35% (23 of 65) of EGFRm-negative tumors. With the TC greater than or equal to 1% threshold, 51% (65 of 128) versus 68% (44 of 65) were mutation-positive and –negative, respectively, and with the TC greater than or equal to 50% threshold, 5% (7 of 128) versus 28% (18 of 65), were mutation-positive and -negative, respectively. For PD-L1 expressors (TC ≥ 1%), median PFS was 18.4 months with osimertinib and 6.9 months with comparator (hazard ratio = 0.30; 95% confidence interval: 0.15–0.60). For PD-L1–negative patients (TC < 1%), median PFS was 18.9 months with osimertinib and 10.9 months with comparator (hazard ratio = 0.37; 95% confidence interval: 0.17–0.74).ConclusionsClinical benefit with osimertinib was unaffected by PD-L1 expression status.     

Breast cancer cells promote CD169+ macrophage-associated immunosuppression through JAK2-mediated PD-L1 upregulation on macrophages

Macrophages are recognized as one of the major cell types in tumor microenvironment, and macrophage infiltration has been predominantly associated with poor prognosis among patients with breast cancer. Using the murine models of triple-negative breast cancer in CD169-DTR mice, we found that CD169⁺ macrophages support tumor growth and metastasis. CD169⁺ macrophage depletion resulted in increased accumulation of CD8⁺ T cells within tumor, and produced significant expansion of CD8⁺ T cells in circulation and spleen. In addition, we observed that CD169⁺ macrophage depletion alleviated tumor-induced splenomegaly in mice, but had no improvement in bone loss and repression of bone marrow erythropoiesis in tumor-bearing mice. Cancer cells and tumor associated macrophages exploit the upregulation of the immunosuppressive protein PD-L1 to subvert T cell-mediated immune surveillance. Within the tumor microenvironment, our understanding of the regulation of PD-L1 protein expression is limited. We showed that there was a 5-fold higher relative expression of PD-L1 on macrophages as compared with 4T1 tumor cells; coculture of macrophages with 4T1 cells augmented PD-L1 levels on macrophages, but did not upregulate the expression of PD-L1 on 4T1 cells. JAK2/STAT3 signaling pathway was activated in macrophages after coculture, and we further identified the JAK2 as a critical regulator of PD-L1 expression in macrophages during coculture with 4T1 cells. Collectively, our data reveal that breast cancer cells and CD169⁺ macrophages exhibit bidirectional interactions that play a critical role in tumor progression, and inhibition of JAK2 signaling pathway in CD169⁺ macrophages may be potential strategy to block tumor microenvironment-derived immune escape.     

Cell integrity indicators assessed by bioelectrical impedance: A systematic review of studies involving athletes

IntroductionBioelectrical impedance analysis (BIA) has been used to evaluate cellular health and integrity through bioelectrical indicators. In the sporting context, monitoring these indicators can be useful to assess the quality and vitality of cells and body tissues.ObjectiveThe aim of this systematic review was to investigate indicators of cellular health and integrity evaluated by BIA in athletes.MethodsSearches were performed in December 2017 in the Lilacs, Medline, PubMed, Science Direct, Scielo, Scopus, SPORTDiscus, and Web of Science databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.ResultsThe searches retrieved 31 articles (30 involving professional athletes and one involving university athletes). In longitudinal studies (n = 15), the bioelectrical parameters directly associated with cellular health and integrity were extracellular water (ECW), phase angle (PA), BIA vector analysis (BIVA), crude reactance data (Xc), resistance (R), and ECW/BCM ratio. Regarding the findings of cross-sectional studies (n = 16), the investigated parameters (ECW, PA, BIVA, Z, BCM, and ECW/BCM) were directly associated with gender, age, sports performance level, modality, and game position.ConclusionsIn the included studies, the cellular health and integrity indicators were: Z, Xc, R, total water, intracellular water, ECW, PA, BIVA, BCM, and ECW/BCM.     

基于PD-1/PD-L1信号通路中医药改善肿瘤免疫抑制微环境研究进展

抑制性共刺激分子程序性死亡因子(PD-1)/程序性死亡因子配体(PD-L1)是重要的免疫负调节因子,在肿瘤免疫逃逸中发挥重要作用。中医药是我国治疗肿瘤的重要手段之一,其主要优势在于增强机体免疫力,重塑肿瘤免疫微环境。本文综述了PD-1/PD-L1信号通路、中医与肿瘤免疫的相关性及中医药干预PD-1/PD-L1信号通路的相关研究,揭示了中医药调节肿瘤免疫多系统、多靶点、多环节、整体性等特点,为中医药防治肿瘤的理论和机制研究提供新的思路。     

二仙汤对去卵巢大鼠心肌微血管及血液流变学的影响

目的:观察去卵巢大鼠心肌微血管密度、微血管内皮细胞形态及血液流变学的变化并探讨二仙汤的干预作用。方法:选用健康10周龄雌性SPF级SD大鼠32只,随机分为假手术组、模型组、雌激素组(戊酸雌二醇,0.18 mg·kg~(-1)),二仙汤组(9 g·kg~(-1))。去卵巢后2周开始灌胃给药,1次/d,连续16周。二仙汤组及雌激素组分别给予二仙汤或戊酸雌二醇灌胃,假手术组和模型组灌胃等体积纯净水。给药16周末,无创超声心动图(UCG)检测心功能;CD34免疫荧光染色法检测心肌微血管密度;透射电镜观测心肌微血管超微结构;放射免疫分析法检测血浆雌二醇(E_2)含量;酶联免疫吸附测定(ELISA)检测血浆内皮素-1(ET-1),前列环素I_2(PGI_2),血栓素A_2(TXA_2),血管内皮生长因子(VEGF)和血管性血友病因子(vWF)水平;凝固法检测凝血四项;血液流变学检测全血黏度和血浆黏度。结果:与假手术组比较,模型组左室射血分数(EF)显著降低(P0.01),左室短轴缩短率(FS)显著降低(P0.01),左室收缩末期容积(LVVols)显著升高(P0.01);心肌微血管密度显著减少(P0.01);心肌微血管内皮细胞肿胀明显,胞浆空化;血浆E_2含量显著降低(P0.01);ET-1,VEGF,vWF含量显著升高(P0.01),前列环素I_2/血栓素A_2(PGI_2/TXA_2)显著降低(P0.01);血浆活化部分凝血酶原时间(APTT)显著降低(P0.01),纤维蛋白原(FIB)含量显著升高(P0.01);全血黏度、血浆黏度、卡松黏度显著升高(P0.01),全血高、低切指数和红细胞聚集指数明显升高(P0.05)。与模型组比较,二仙汤组大鼠EF,FS明显升高(P0.05),LVVols明显降低(P0.05);微血管密度显著增多(P0.01);心肌微血管内皮细胞水肿改善,运输小泡清晰可见;血浆E_2显著升高(P0.01);ET-1,VEGF显著降低(P0.01),PGI_2/TXA_2显著升高(P0.01);APTT显著升高(P0.01);全血黏度、全血高切相对指数、红细胞聚集指数明显降低(P0.05),卡松黏度、血浆黏度显著降低(P0.01)。结论:二仙汤增加去卵巢大鼠心肌微血管密度、保护微血管内皮细胞结构的完整性,改善其内皮分泌功能和血液流变学,保护心功能。     

银杏叶提取物注射液联合醋酸泼尼松治疗突发性耳聋的疗效观察

目的:探析银杏叶提取物注射液联合醋酸泼尼松治疗突发性耳聋的疗效。方法:选取2017年6月-2019年3月期间我院耳鼻喉科收治的96例突发性耳聋患者,按随机数表法为研究组(48例)和对照组(48例)。给予对照组醋酸泼尼松治疗,而研究组在对照组基础上增加银杏叶提取物注射液治疗,比较两组治疗效果、中医证候积分、血液流变学指标[血细胞比容(Hematocrit,HCT)、血浆黏度(Plasma Viscosity,PV)、红细胞聚集指数(Erythrocyte Aggregation Index,EAI)]以及不良反应。结果:研究组治疗总有效率较对照组更高,差异有统计学意义(P<0.05);治疗后,研究组中医证候积分、HCT、PV及EAI水平均明显低于治疗前和对照组,差异有统计学意义(P<0.05);两组均未出现不良反应。结论:银杏叶提取物注射液联合醋酸泼尼松治疗突发性耳聋安全、高效,可显著改善患者血液流变学,临床推广与应用价值较高。