目前在重症加强治疗病房(intensive care unit,ICU)超过60％的患者需要气管插管[1],同时作为一种高风险侵入性治疗方式,对于部分疾病引起的生理性气道困难,或因肥胖和怀孕等导致的解剖困难,可导致插管困难或不及时,插管过程中易发生低氧血症、血流动力学不稳定、凝血障碍、呼吸机相关性肺炎等,严重时可导致心搏骤停[2-3].自Frumin等[4]在1959年首次通过鼻导管对手术患者插管前给予预充氧,再到2015年有关指南建议所有插管的患者都应预充氧[5],预充氧技术取得了较大的发展.

慢性阻塞性肺疾病(简称慢阻肺)严重危害人类健康,是目前世界上病死率最高的疾病之一.据估计到2030年慢阻肺可能成为慢性疾病死亡的第三大病因,而慢阻肺急性加重又是慢阻肺患者死亡的主要原因[1-3].慢阻肺急性加重多由急性感染诱发,其病理生理学特点为肺过度充气、呼吸肌疲劳及顺应性下降,导致低氧血症、CO2潴留及呼吸衰竭等,临床上表现为呼吸困难加重、痰量增多、痰液变稠等[4-5].基于此,积极抗感染、支气管舒张剂的应用及呼吸支持治疗成为慢阻肺急性加重的主要治疗手段.

Objective:To evaluate the prognostic value of red blood cell distribution width （RDW） in patients with acute respiratory failure.Methods:Data of patients with acute respiratory failure according to the international ICD9-CODE diagnostic code was extracted from MIMIC Ⅲ database. Demographic data， combordities， laboratory results， SOFA score were collected. The primary outcome were the 28-day and 90-day mortality. Secondary outcome included ICU mortality， in-hospital mortality， length of ICU stay and length of hospital stay. All subjects were divided into the high RDW group and the normal RDW group according to the best ROC cutoff value. The baseline and clinical outcomes of the two groups were compared. Kaplan-Meier survival curve was used to analyze the cumulative survival rate at 28 days and 90 days in the two groups. Cox proportional hazard regression model was used to analyze the mortality risk of patients with acute respiratory failure at 28 days and 90 days. The area under the receiver operating characteristic （ROC） was also calculated.Results:A total of 6286 patients with acute respiratory failure were incluced into final analysis. Compared with normal RDW group， the mortality rate at 28 day （21.3% vs 33.7%， P＜0.001） and 90 day （27.8% vs 44.8， P＜0.001） were significant higher in high RDW group. After propensity score matched （PSM） similar results were found in 28-day mortality rate （25.9% vs 31.9%， P＜0.001） and 90-day mortality rate （33.5% vs 43.1%， P＜0.001） . The cumulative survival analysis revealed that the mortality rate was significant higher in high RDW group. Cox proportional hazards regression model analysis showed that RDW was significant associated with 28- and 90-day mortality in patients with acute respiratory failure. There was no significant difference of the area under ROC curve between RDW and SOFA in prediction value of 28-day mortality （0.663 vs 0.662， P=0.926）. However， RDW performed a better predictive value than SOFA score on the 90-day mortality （0.678 vs 0.651， P=0.003）.Conclusion:RDW may be a valuable prognostic indicator in patients with acute respiratory failure.

Abstract. Cell death occurs in various tissues and organs in the body. It is a physiological or pathological process that has different effects. It is of great significance in maintaining the morphological function of cells and clearing abnormal cells. Pyroptosis, apoptosis, and necrosis are all modes of cell death that have been studied extensively by many experts and scholars, including studies on their effects on the liver, kidney, the heart, other organs, and even the whole body. The heart, as the most important organ of the body, should be a particular focus. This review summarizes the mechanisms underlying the various cell death modes and the relationship between the various mechanisms and heart diseases. The current research status for heart therapy is discussed from the perspective of pathogenesis.

目的 通过文献计量学和可视化分析研究重症新型冠状病毒肺炎前沿问题.方法 检索Web of Science数据库中2020年1月至2020年11月发表的重症新型冠状病毒肺炎文献,应用Excel和CiteSpace软件进行文献计量分析和可视化分析.结果 共纳入1176篇文献,从国家/地区、期刊、机构发文量进行计量学分析可知,美国和中国对重症新型冠状病毒肺炎的研究最为广泛,研究机构以高校居多,Critical Care期刊发文量最多.从作者合作、关键词共现和聚类、文献共被引进行文献可视化分析可知,本国不同作者间的合作关系密切,同一机构的不同作者更易形成合作关系,但是国际合作较少.该研究领域关注的热点为重症患者、临床表现、实验室检查和治疗,而且高被引文献关注的焦点与关键词方向一致.结论 当前重症新型冠状病毒肺炎的临床表现、诊断、治疗是人们关注的热点,医务工作者应深化国际间合作,为未来的研究提供有力的参考依据.

脓毒症是重症监护病房的常见疾病,具有高发病率、高死亡率的特点,易发生全身多器官损伤甚至衰竭.当前,脓毒症的治疗以病因治疗、液体复苏、抗感染等目标为主,由于病情进展迅速导致治疗效果欠佳.线粒体自噬可通过Parkin依赖性途径和Parkin非依赖性途径清除受损、老化和功能障碍的线粒体,有效避免细胞过度损伤,维持细胞内环境稳态,在许多疾病中发挥重要作用.线粒体自噬在Parkin、Fun14结构相关蛋白1、Bcl-2相互作用蛋白3、线粒体动力学相关蛋白1介导下能够抑制炎症因子和活性氧的释放,减少多器官功能障碍的发生,其在脓毒症中发挥保护作用.本文对线粒体自噬在脓毒症中的作用机制和治疗方面进行综述,旨在为脓毒症的治疗提供新的依据.

Sepsis is a common syndrome with high mortality in ICU, which lead to MODS. Septic acute kidney injury (SAKI) has a high incidence and is associated with poor prognosis. The lack of comprehensive understanding of the pathogenesis of AKI is an important obstacle to its early diagnosis and treatment. However, more and more studies have confirmed that cell cycle arrest, as an early protective mechanism of the kidney, is a kind of important molecules mechanism and an important factor in the pathophysiological process in SAKI which can be treated as a target to avoid the replication of damaged DNA. We summarized the mechanism of cell cycle arrest in SAKI, as well as the markers of cell cycle block in this manuscript. We hope cell cycle block can be used as a potential therapeutic target for early prevention and improvement of prognosis of AKI.

目的 研究艾司洛尔(Esmolol,ES)是否可通过抑制焦亡的经典通路进而发挥心脏保护作用.方法 72只大鼠随机分为假手术(sham operation,Sham)组、盲肠结扎穿孔(cecal ligation and puncture,CLP)组和ES组,每组24只.每组随机抽取8只大鼠观察生存情况,剩余16只大鼠根据处理时间分为6 h和24 h两个亚组,每组8只.Sham组仅给予开腹,翻动盲肠处理;CLP组和ES组采用CLP法建立脓毒症大鼠模型.Sham组、CLP组持续经大鼠左颈内静脉泵入生理盐水6 h;ES组持续泵入艾司洛尔稀释液6 h.分别于相应时间点处死大鼠,采用酶联免疫吸附法(ELISA)测定血清IL-1β、IL-18水平,采用免疫印迹法(Western blot)检测心肌组织NLRP3、Caspase-1及GSDMD蛋白表达水平;光学显微镜下观察心肌病理改变;荧光显微镜下观察心肌细胞焦亡情况.结果 ①ELISA结果显示,与各时间点的Sham组比较,ES组大鼠血清IL-1β及IL-18水平均明显升高,24 h组最高;而与CLP组比较,上述因子水平在6 h与24 h均明显下降(P<0.05).②Western blot结果显示,术后各时间点,大鼠心肌组织中焦亡经典通路相关蛋白[NOD样受体蛋白3(nucleotide-binding domain(NOD)-like receptor protein 3,NLRP3)、天冬氨酸蛋白水解酶-1(cysteinyl aspartate-specific proteases-1,Caspase-1)、消皮素D(Gasdermin D,GSDMD)]在CLP组均显示出高表达状态,较Sham组明显升高(P<0.05),24 h组表达量最高,而ES组各时间点上述蛋白表达水平均较CLP组有所减少,且差异统计学意义(P<0.05).③病理结果显示,Sham组大鼠心肌组织可见轻微的病理损伤,CLP组心肌细胞损伤最重,ES组大鼠的心肌细胞破坏较CLP组减轻程度多,各组24 h损伤程度均较6 h重.④24 h Tunel与DAPI染色显示,与Sham组可见的少量阳性细胞比较,CLP组可见大量被染色的阳性细胞,且差异有统计学意义(P<0.05);而与CLP组比较,ES组心肌细胞阳性染色数量明显减少(P<0.05).⑤7 d生存分析显示,CLP组大鼠死亡率最高,ES组大鼠生存天数较CLP组明显延长,差异有统计学意义(P<0.01).结论 ES能减轻心肌损伤,提高脓毒症大鼠生存率,其机制可能与抑制焦亡经典通路中NLRP3/Caspase-1/GSDMD蛋白表达及减少炎症因子释放有关.

目的 探讨血清阴离子间隙(AG)对脓毒症患者预后的预测价值.方法 用结构化查询语言(SQL)提取重症监护医学数据库(MIMIC-Ⅲ)中符合纳入标准的脓毒症患者资料,以患者28 d病死率、90 d病死率、院内病死率、ICU病死率为临床结局指标.所有研究对象根据血清AG数值,以四分位间距分成四组,比较四组患者的基线数据,并评估血清AG与临床结局指标的关系.使用Kaplan-Meier生存曲线和Cox回归预测曲线探索各组患者与主要结局指标的关系,并用log-rank检验评估生存差异.为校正潜在的混杂因素,建立不同的Cox风险回归模型进行多因素回归分析.此外用受试者工作特征(ROC)曲线下面积(AUC)评估血清AG对脓毒症患者28 d病死率、90 d病死率的预测价值.为探索血清AG与基础疾病对脓毒症患者28 d病死率的相关性,进行了亚组分析.结果 共纳入12484例脓毒症患者,分别为Q1组(AG<12 mmol/L,n=2451)、Q2组(12 mmol/L≤AG<14 mmol/L,n=2724)、Q3组(14 mmol/L≤AG<17 mmol/L,n=3959)和Q4组(AG≥17 mmol/L,n=3350),结果发现,随着血清AG升高,Q1～Q4组28 d病死率(12.5％、14.1％、19.2％、29.5％,P<0.001),90 d病死率(20.9％、23.3％、27.0％、39.1％,P<0.001),院内病死率(11.0％、13.9％、17.7％、28.1％,P<0.001),ICU病死率(10.1％、12.0％、15.6％、25.7％,P<0.001)差异均有统计学意义.在Kaplan-Meier生存曲线中发现,随着患者住院时间的延长,血清AG越高,患者的生存率下降越明显,Log-rank检验提示有明显的生存差异(P<0.001),并与Cox回归预测曲线高度重合.在不同Cox比例风险回归模型中,以Q1为参照组,在28 d、90 d病死率中,模型1中(未校正),Q2～Q4组HR值分别从1.14上升到2.60、1.13上升到2.14(P<0.001);在模型2中(校正了年龄、性别),Q2～Q4组HR值分别从1.12上升到2.62、1.12上升到2.17(P<0.001);在模型3中(模型2基础上调整了血钠+、血钾+等),Q2～Q4 HR值分别从1.07上升到1.53、1.07上升到1.37(P<0.001).ROC曲线下分析发现,血清AG、血乳酸以28 d病死率为因变量时,AUC分别为0.625、0.624(P=0.918);以90 d病死率为因变量时,为0.603、0.613(P=0.174).此外亚组分析中发现,随着血清AG的升高,脓毒症合并充血性心力衰竭患者28 d病死率会更高.结论 血清AG可能是脓毒症患者短期预后的有效预测指标.

急性呼吸窘迫综合征( acute respiratory distress syndrome,ARDS)是由不同病因引起的以弥漫性肺泡损伤为其主要特点的急性肺损伤,临床主要表现为持续性低氧血症、呼吸窘迫及呼吸衰竭,是重症监护室( intensive care unit, ICU )最常见的疾病之一[1].其中呼吸支持治疗是其核心治疗方式之一.

Objective To provide theoretical basis for the clinical application of pyroptosis, we analyzed the related literature of focal death to understand the research prospects and hot spots in recent ten years. Methods We searched the Web of Science for all the literature related to pyroptosis from 2009 to 2019. CiteSpace software was used for bibliometric analysis. Using the generated network map to evaluate and infer the characteristics of pyroptosis in several indicators, such as author, country, institution, key words and references. Results 1389 literatures related to pyroptosis from 2009 to 2019 were published. The number of articles published in each year is increasing rapidly with the year. St Jude Childrens Res Hosp became the largest publishing agency. There is active cooperation among authors in various fields. The United States is a major contributor to the articles in the field of pyroptosis. Biology, molecular science and immunology have become the main research subjects. The main hot topics include cell death, apoptosis and activation. Conclusions In recent years, the research form of pyroptosis has gradually increased, and the research scope has become larger and larger, research depth is also deeper and deeper. We should consider how to further explore its value in future research, so that it can better serve medicine and human beings. DOI: 10.11855/j.issn.0577-7402.2020.08.07