摘要：Immune evasion behavior and immunosuppressive characteristics of tumor extensively impedethe immune initiation effect of therapy triggered immunogeniccell death (ICD). In this work, a carrier-adjuvantedimmunostimulator (designated as CoCeC) is developed toboost photodynamic immunotherapy by downregulatingprogrammed death ligand 1 (PD-L1) and impairing adenosinetriphosphate (ATP) hydrolysis. Among these, the crosslinkedchitosan oligosaccharide is applied as the drug carrier fordelivery of Ce6 and Ceritinib, which also serves as an immuneadjuvant to downregulate PD-L1. Meanwhile, the robustphotodynamic therapy (PDT) of CoCeC exhibits lethal toxicityagainst tumor cells to induce ICD and release damage-associated molecular patterns (DAMPs), which can also impairATP hydrolysis by blocking CD39. In vitro and in vivo resultsdemonstrate the robust therapeutic efficacy of CoCeC tosuppress primary tumor growth and activate a superior immune elimination against lung metastasis by amplifying theimmune initiation of ICD with the assistance of immune *** work provides a self-adjuvanted strategy to enhance the immune response of therapy induced ICD, which ispromising to activate systemic antitumor immunity in consideration of the complicated immunosuppressive factors.

摘要：Cough is a defensive behavior that protects the respiratory system from infection and clears airway *** airflow dynamics have been analyzed by a variety of mathematical and experimental *** this paper,the cough airflow dynamics of 42 subjects were obtained and *** identification model based on piecewise Gauss function for cough airflow dynamics is proposed through the dimensionless method,which could achieve over 90%identification ***,an assisted cough system based on pneumatic flow servo system is *** vacuum situation and feedback control are used to increase the simulated peak cough flow rate,which are important for airway secretion clearance and to avoid airway collapse,*** simulated cough peak flow could reach 5 L/s without the external assistance such as manual pressing,patient cooperation and other ***,the backstepping control is developed to generate a simulated cough airflow that closely mimics the natural cough airflow of *** assisted cough system opens up wide opportunities of practical application in airway secretion clearance for critically ill patients with COVID 2019 and other pulmonary diseases.

摘要：There is a pressing need for effective therapeutics for coronavirus disease 2019(COVID-19),the respiratory disease caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)*** process of drug development is a costly and meticulously paced process,where progress is often hindered by the failure of initially promising *** aid this chal-lenge,in vitro human microphysiological systems need to be refined and adapted for mechanistic studies and drug screening,thereby saving valuable time and resources during a pandemic *** SARS-CoV-2 virus attacks the lung,an organ where the unique three-dimensional(3D)structure of its functional units is critical for proper respiratory *** in vitro lung models essentially recapitulate the distinct tissue structure and the dynamic mechanical and biological interactions between different cell *** model systems include Transwell,organoid and organ-on-a-chip or microphysiological systems(MPSs).We review models that have direct relevance toward modeling the pathology of COVID-19,including the processes of inflammation,edema,coagulation,as well as lung immune *** also consider the practical issues that may influence the design and fabrication of *** role of lung MPS is addressed in the context of multi-organ models,and it is discussed how high-throughput screening and artificial intelligence can be integrated with lung MPS to accelerate drug development for COVID-19 and other infectious diseases.

摘要：Background Chronic obstructive pulmonary disease(COPD)is a severe public health *** smoke(CS)is a risk factor for COPD and lung *** underlying molecular mechanisms of CS-induced malignant transformation of bronchial epithelial cells remain *** this study,we describe a lung-on-a-chip to explore the possible mechanistic link between cigarette smoke extract(CSE)-associated COPD and lung *** An in vitro lung-on-a-chip model was used to simulate pulmonary epithelial cells and vascular endothelial cells with *** levels of IL-6 and TNF-αwere tested as indicators of inflammation using an enzyme-linked immune sorbent *** junction complex mRNA expression was detected with qRT-PCR as the index of epithelial-to-mesenchymal transition(EMT).The effects of CSE on the phosphorylation of signal transduction and transcriptional activator 3(STAT3)were detected by Western *** cytometry was performed to investigate the effects of this proto-oncogene on cell cycle *** Inflammation caused by CSE was achieved in a lung-on-a-chip model with a mimetic *** exposure induced the degradation of intercellular connections and triggered the EMT *** exposure also activated the phosphorylation of proto-oncogene STAT3,while these effects were inhibited with *** CSE exposure in the lung-on-a-chip model caused activation of STAT3 in epithelial cells and endothelial ***0152,an inhibitor of activated STAT3,could be a potential treatment for CS-associated COPD and lung cancer.

摘要：在5年前的JAMA杂志上，我称赞了从事重症监护专业的人员，因为他们开始认真地对肺动脉插管（pulmonary artery catheterization，PAC）在高危手术患者和重症监护（ICU）患者中的疗效进行评估，这是一项很困难的工作。我之所以这么认为，是因为自20世纪70年代该技术在临床出现后的，它已经被广泛应用于ICU和围手术期患者，但目前仍缺乏高质量的证据支持其应用。1996年发表的一项回顾性观察研究表明，使用PAC可能会引起不良的结局。因此，采用前瞻性随机化研究设计对PAC进行合理研究是从当前临床实践中“后退”的严格而必要的一步，这决不是一个简单的过程。在本期JAMA杂志中发表了2篇重要的关于这一评估过程的文章，这使我们得以及时回顾近期的研究，并思考从中获得的信息。

摘要：本文讨论了芝加哥伊利诺伊大学研发的几种用于人胰岛生理和病理生理学研究的微流体装置及其在人胰岛移植中的应用。首先介绍了作为l型糖尿病临床治疗的胰岛移植领域关键问题。随后,回顾了可以解决这些关键问题的微流体装置、每一种微流体装置的独特之处及他们的应用。此外,本文也简单地讨论了芝加哥伊利诺伊大学这几种微流体装置的设计和制造原理。

摘要：背景Smart Bag MO是一种设计用于成人的流量限制型球囊面罩装置，它可减少在无气道保护的情况下发生胃反流的风险。其在严重气道梗阻时的应用特性尚不明确。方法建立Bench模型以模拟无气道保护情况下发生呼吸暂停的患者，分别使用流量限制型球囊装置和标准球囊装置通气。测定并对比两者在气道阻力为4、10、20cmH2O·L-1·S-1时的呼吸力学和潮气量。结果使用流量限制型球囊装置较标准球囊装置能延长吸气时间。流量限制型球囊装置和标准球囊装置在模拟无气道梗阻组中肺潮气量分别为750±70ml和780±30ml（无统计学差异）；模拟中度气道梗阻组中肺潮气量分别为800±70ml和850±20ml（无统计学差异）；模拟严重气道梗阻组中肺潮气量分别为210±20ml和170±10ml（P〈0．01）。流量限制球囊装置和标准球囊装置在模拟无气道梗阻组中气道峰压分别为15±2cmH2O和22±4cmH2O（P〈0．01）；模拟中度气道梗阻组中气道峰压分别为22±1cmH2O和39±7cmH，O（P〈0．01）；模拟严重气道梗阻组中气道峰压分别为26±1cmH，O和61±3cmH，O（P〈0．01）。流量限制球囊装置和标准球囊装置在模拟无气道梗阻组中的胃胀气速率为0ml／min；模拟中度气道梗阻组中速率分别为0ml／min和200±20ml／min（P〈0．01）；模拟严重气道梗阻组中速率分别为0ml／min和1240±50ml／min（P〈0．01）。结论在模拟严重气道梗阻组中，与标准球囊装置相比，流量限制型球囊装置能延长吸气时间、增大潮气量、降低气道压并能避免胃胀气的发生。

摘要：目的分析癌症患者疼痛程度、疲劳程度与生活质量之间的关系。方法采用横断面研究设计。应用便利抽样法于2019年5-11月选取两省两所三级甲等医院224例接受化疗且符合入选标准的癌症患者进行调查。采用一般资料调查表、简明疲劳量表(Brief Fatigue Inventory,BFI)、疼痛数字评分量表(The Nume-rical Rating Scale,NRS)和由欧洲癌症治疗和研究组织编制的生活质量量表(The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire,EORTCQLQ-C30)收集资料。结果在报告过去24 h最严重的疼痛情况时,85例(37.9%)有轻度疼痛,121例(54.0%)有中度疼痛,18例(8.0%)有重度疼痛。此外,92例(41.1%)患者有轻度疲劳,72例(32.1%)有中度疲劳,60例(26.8%)有重度疲劳。大多数轻度疼痛的患者仅经历轻度疲劳,其生活质量也处于中等水平。中度和重度疼痛患者大多有中度或更高程度的疲劳(r=0.296,P<0.01)和较低的生活质量(r=-0.141,P<0.01)。轻度疼痛患者中,疲劳与生活质量间不存在相关性(r=-0.179,P=0.104)。中、重度疼痛患者的疲劳与生活质量呈负相关(r=-0.537,P<0.01;r=-0.509,P<0.05)。结论中、重度疼痛患者的疲劳症状比轻度疼痛患者更重,生活质量也更低。护士应更关注中重度疼痛患者,探索症状间的相互作用机制,开展症状联合干预,以提高患者生活质量。

摘要：背景:实时定量PCR技术在微生物包括分枝杆菌检测领域应用越来越广泛。目的:评价在痰标本涂片抗酸染色无法获得诊断信息时(如没有痰或痰涂片阴性),RT-PCR在结核病诊断中的作用。设计:我们分析了从2006年1月至2008年4月之间连续纳入的为诊断结核病而进行的支气管分泌物RT-PCR检测的病人。所有病人均接收了计算机断层扫描(CT)、支气管镜和组织活检确诊结核病,对收集的支气管分泌物进行了微生物学和RT-PCR检测。最终的确诊基于微生物学或临床病理学的标准。结果:有136例患者最终得到了诊断结果,其中77例(包括65例培养阳性病例)诊断为结核。RT-PCR在确诊病人中的阳性率是51.9%(40/77)。与支气管分泌物抗酸染色相比,更多的病人(20.8%)通过RT-PCR被检测出来(40比20,P<0.001)。结合支气管分泌物抗酸染色和RT-PCR,77例结核确诊病例中的44例(57.1%)在几天之内被确诊。结论:支气管分泌物的RT-PCR检测在涂阴或无痰结核病人的快速诊断中是一种有用的方法。

摘要：流感病毒和新型冠状病毒(SARS-CoV-2)是近年来频繁引发呼吸道疾病的主要病原,其引起的黏膜免疫应答对于病毒的控制和清除至关重要.目前对于SARS-CoV-2感染后肺部黏膜免疫应答的具体调控机制及其与流感感染的区别尚不清楚我们通过原位杂交-多重免疫荧光染色技术及空间转录组学揭示了流感病毒和SARS-CoV-2感染过程中局部免疫应答的动态变化过程,并发现相比于流感病毒感染,SARS-CoV-2感染早期肺部黏膜会更加快速地形成诱导性支气管相关淋巴组织(iBALT)结构并活化B1细胞产生较高水平IgM和IgA,可能在抗病毒感染及iBALT的形成中发挥重要作用.同时,SARS-CoV-2及表达其S蛋白的假病毒感染均能够促进小鼠和人的B1细胞的活化.将表达S蛋白的腺病毒疫苗AdC7-S对小鼠进行免疫后,可以成功诱导出包含B1细胞的iBALT,并在病毒感染中发挥保护作用.本研究揭示了呼吸道病毒引起的肺脏黏膜免疫动态应答过程,并阐明了SARS-CoV-2感染早期B1细胞的活化特点及免疫保护作用,为揭示新发呼吸道传染病的保护性应答机制及疫苗设计提供了理论基础.