Sepsis-associated encephalopathy (SAE) is a serious complication of sepsis that can lead to high mortality and poor neurological outcomes. Current diagnostic methods, whether based on clinical scores or brain images, remain inaccurate. We aimed to formulate a multimodal model that incorporated three-dimensional (3D) magnetic resonance imaging (MRI) neuroanatomical characteristics with clinical scores to improve SAE detection. In this retrospective case-control study, 35 healthy controls and 72 patients with sepsis (34 SAE, 38 non-SAE) were included and scanned using 3D T1-weighted MRI. Whole-brain segmentation was performed using FreeSurfer software. Clinical characteristics, including age, gender, and clinical scores (Acute Physiology and Chronic Health Evaluation II [APACHE II] and Sequential Organ Failure Assessment [SOFA]), were captured within the electronic health record data. Feature selection was performed using LASSO regression with 10-fold cross-validation exclusively on the training set. We trained eight machine learning models based on a combination of clinical scores and neuroimaging features, with hyperparameter tuning conducted via GridSearchCV using 3-fold stratified cross-validation. The performance of each model was evaluated based on stratified hold-out validation, and SHapley Additive exPlanations (SHAP) analysis was used to interpret the optimal model. Rigorous quality control procedures were applied, and 540 features were analyzed across the three groups. We identified 27 reliable indicators associated with SAE, including clinical scores (APACHE II and SOFA) and neuroanatomical characteristics (hippocampus, thalamus, amygdala, lateral ventricle, and globus pallidus). Among eight machine learning models trained and evaluated, the XGBoost model displayed significantly superior discrimination and calibration performance, achieving an area under the receiver operating characteristic curve (AUC) of 0.92. Key predictors included APACHE II, SOFA, and volumetric changes in cerebellar cortex, hippocampus, and amygdala. SHAP analysis revealed nonlinear relationships wherein elevated clinical scores and neuroanatomical atrophy predicted SAE. This multimodal model integrates clinical scores and neuroimaging features of SAE and demonstrates promising discriminative ability in differentiating healthy controls, septic patients without SAE, and SAE patients. The findings provide candidate neuroimaging metrics that may aid in diagnosis and offer potential insights into the structural correlates of SAE. However, these results are preliminary and require prospective validation in larger, multi-center cohorts before clinical translation.

Background: Hypoalbuminemia has been proven to be an independent risk factor for poor prognosis in sepsis. This study attempts to provide a better understanding of the differences in sepsis-related hypoalbuminemia to facilitate efficient identification of high-risk patients by clinicians. Methods: We collected and analyzed data on 1827 patients with sepsis from the intensive care unit (ICU) retrospectively. Based on their serum albumin levels, the patients were classified into two groups: hypoalbuminemia (n=1405) and non-hypoalbuminemia (n=422). The pathogens were identified based on the results of the blood cultures. We conducted propensity score matching (PSM) to balance baseline characteristics across pathogen groups and minimize confounding factors. Results: Fourteen species of the most frequently detected pathogens were identified based on blood culture results from patients with sepsis. Eight species of pathogens, including Candida, Klebsiella, Acinetobacter baumannii, Staphylococcus, Pseudomonas, Streptococcus, Enterococcus, and Escherichia coli, caused a significantly higher risk of developing hypoalbuminemia than other pathogen infections, all with statistical differences (p<0.05). Restricted cubic spline (RCS) analysis showed a U- or L-shaped relationship between serum albumin levels and 28-day all-cause mortality, with critical values that differed across the different species of pathogens. The L-shaped forms of Candida, Staphylococcus, Enterococcus, and Escherichia coli had albumin cut-off values of 30.36 g/L, 32.27 g/L, 30.46 g/L, and 30.95 g/L, respectively. While Bacteroides fragilis exhibited a U-shaped relationship with albumin cut-off values of 33.41 g/L and 39.42 g/L. Conclusion: Our findings highlight the significance of meticulous surveillance of serum albumin levels in septic patients exposed to different species of pathogens. It is essential to pay attention to the pathogen-specific albumin threshold, not only for the efficient identification of high-risk patients, but also for prompt therapeutic interventions that can improve patient prognosis.

BackgroundNeuroinflammation assumes a pivotal role in both the etiological underpinnings and the dynamic progression of sepsis-associated encephalopathy (SAE). The occurrence of cognitive deficits with SAE is associated with neuroinflammation. 4-phenyl butyrate (4-PBA) may control inflammation by inhibiting endoplasmic reticulum stress (ERS). The primary objective of this investigation is to scrutinize the effectiveness of 4-PBA in mitigating neuroinflammation induced by lipopolysaccharides (LPS) and its consequent impact on cognitive function decline.MethodsLPS-injected mice with SAE and LPS-treated BV2 cell were established to serve as experimental paradigms, both contributing to the investigative framework of the study. Cognitive functions were assessed by behavioral tests. Hippocampal neuronal damage was assessed using Golgi staining and Nissl staining. Quantitative PCR assay and immunofluorescence were used to analyze neuroinflammation. Mitochondrial function was examined using transmission electron microscopy. Protein expression analysis was conducted through the application of western blotting methodology, serving as the investigative approach to elucidate molecular signatures in the experimental framework. Endoplasmic reticulum and mitochondrial calcium flow were detected using flow cytometry. To delve deeper into the mechanistic intricacies, the administration of 4μ8c was employed to selectively impede the IRE1α/Xbp1s pathway, constituting a strategic intervention aimed at elucidating underlying regulatory processes.ResultExpression levels of ERS-related proteins exhibited a significant upregulation in hippocampal tissues of LPS-treated mice when compared to wild-type (WT) counterparts. The administration of 4-PBA notably ameliorated memory deficits in LPS-treated mice. Furthermore, 4-PBA treatment was found to alleviate oxidative stress and neuroinflammation. Mechanistically, the IRE1α/Xbp1s-Ca2+ signaling pathway played a crucial role in mediating the beneficial effects of mitigating oxidative stress and maintaining mitochondrial calcium homeostasis, with inhibition of the IRE-related pathway displaying opposing effects.ConclusionOur results suggest that administration of 4-PBA treatment significantly attenuates ERS, alleviates cognitive decline, reduces inflammatory damage, and restores mitochondrial dynamics via the IRE1α/Xbp1s-Ca2+-associated pathway, which provides a new potential therapeutic approach to SAE.

目的:探索以病例为基础的人工智能—仿真模拟教学在急危重症教学中的有效性.方法:选取临床医学本科实习生,接受人工智能—仿真模拟教学,对教学效果进行量化评价.结果:试验组临床技能考核成绩及临床诊治思维能力评价高于对照组(P＜0.01).结论:以病例为基础的人工智能—仿真模拟教学在急危重症教学中的应用是有效的.

Background Lipopolysaccharide, a highly potent endotoxin responsible for severe sepsis, is the major constituent of the outer membrane of gram-negative bacteria. Endothelial cells participate in both innate and adaptive immune responses as the first cell types to detect lipopolysaccharide or other foreign debris in the bloodstream. Endothelial cells are able to recognize the presence of LPS and recruit specific adaptor proteins to the membrane domains of TLR4, thereby initiating an intracellular signaling cascade. However, lipopolysaccharide binding to endothelial cells induces endothelial activation and even damage, manifested by the expression of proinflammatory cytokines and adhesion molecules that lead to sepsis. Main findings LPS is involved in both local and systemic inflammation, activating both innate and adaptive immunity. Translocation of lipopolysaccharide into the circulation causes endotoxemia. Endothelial dysfunction, including exaggerated inflammation, coagulopathy and vascular leakage, may play a central role in the dysregulated host response and pathogenesis of sepsis. By discussing the many strategies used to treat sepsis, this review attempts to provide an overview of how lipopolysaccharide induces the ever more complex syndrome of sepsis and the potential for the development of novel sepsis therapeutics. Conclusions To reduce patient morbidity and mortality, preservation of endothelial function would be central to the management of sepsis. Graphical Abstract

TanshinoneⅡA (TanⅡA) is a noteworthy lipophilic diterpene compound derived from the dried roots of the Traditional Chinese Medicine Danshen () that has various pharmacological properties, including anti-inflammatory, antibacterial, and antioxidative effects. Sepsis is a life-threatening organ dysfunction induced by a dysregulated host response to infection. Recently, increasing attention has been paid to sepsis-induced dysfunction of the intestine, car-diovascular system, lungs, kidneys, liver, and other organs. Experimental studies have shown that TanⅡA has therapeutic potential for sepsis-induced organ dysfunction owing to its anti-inflammatory, anti-apoptotic and regulatory effects on multiple signalling pathways. The purpose of this article is to evaluate the potential multiorgan protective effects of TanⅡA in sepsis.

Sepsis is a life-threatening organ dysfunction caused by an abnormal infection-induced immune response. Despite significant advances in supportive care, sepsis remains a considerable therapeutic challenge and is the leading cause of death in the intensive care unit (ICU). Sepsis is characterized by initial hyper-inflammation and late immunosuppression. Therefore, immune-modulatory therapies have great potential for novel sepsis therapies. Ubiquitination is an essential post-translational protein modification, which has been known to be intimately involved in innate and adaptive immune responses. Several E3 ubiquitin ligases have been implicated in innate immune signaling and T-cell activation and differentiation. In this article, we review the current literature and discuss the role of E3 ligases in the regulation of immune response and their effects on the course of sepsis to provide insights into the prevention and therapy for sepsis.

IntroductionThe ubiquitin system is an evolutionarily conserved and universal means of protein modification that regulates many essential cellular processes. Endothelial dysfunction plays a critical role in the pathophysiology of sepsis and organ failure. However, the mechanisms underlying the ubiquitination-mediated regulation on endothelial dysfunction are not fully understood.Areas coveredHere we review the advances in basic and clinical research for relevant papers in PubMed database. We attempt to provide an updated overview of diverse ubiquitination events in endothelial cells, discussing the fundamental role of ubiquitination mediated regulations involving in endothelial dysfunction to provide potential therapeutic targets for sepsis.Expert opinionThe central event underlying sepsis syndrome is the overwhelming host inflammatory response to the pathogen infection, leading to endothelial dysfunction. As the key components of the ubiquitin system, E3 ligases are at the center stage of the battle between host and microbial pathogens. Such a variety of ubiquitination regulates a multitude of cellular regulatory processes, including signal transduction, autophagy, inflammasome activation, redox reaction and immune response and so forth. In this review, we discuss the many mechanisms of ubiquitination-mediated regulation with a focus on those that modulate endothelial function to provide potential therapeutic targets for the management of sepsis.

It has been reported that angiopoietin 2 (Ang-2) plays an integral role in the pathophysiology of sepsis and many other inflammatory diseases. However, the specific role of Ang-2 in septic shock has not been defined. The aim of the present study was to assess the predictive value of serum Ang-2 in patients with septic shock. Clinical data of 85 patients with septic shock and 10 healthy controls admitted to the intensive care unit with a diagnosis of septic shock were collected between January 2020 and October 2020 at Tongji Hospital (Wuhan, China). The serum levels of Ang-2 mRNA were quantified using a quantitative real-time PCR assay. Ang-2, SOFA and APACHE II scores were retrospectively analyzed in relation to 28-day mortality. The area under the receiver operating characteristic (ROC) curve (AUC) was used to discriminate the accuracy of the prediction. Mean Ang-2 mRNA levels in the patients with septic shock were significantly higher than those in the healthy controls (P<0.05), and the Ang-2 levels showed a downwards trend over time following treatment. The three indicators (AUCs, SEMs, P-values) were Ang-2 (0.82, 0.03, P<0.01), SOFA score (0.76, 0.04, P<0.01), and APACHE II score (0.73, 0.04, P<0.01). The present study confirmed that Ang-2 mRNA levels were significantly elevated in septic shock. The Ang-2 mRNA level at ICU admission in a patient with septic shock could be a predictive biomarker for mortality.

目的 观察丹参酮ⅡA对脓毒症大鼠血管内皮细胞保护作用,并探讨可能机制.方法 2019年1—12月于华中科技大学同济医学院附属同济医院进行实验.SD大鼠36只采用随机数字表法分为对照组、脓毒症组和丹参酮ⅡA治疗组,每组12只.对照组仅采用盲肠探查术,脓毒症组和丹参酮ⅡA干预组均采用盲肠结扎法制备脓毒症大鼠模型,丹参酮ⅡA干预组术后予以丹参酮ⅡA注射液20 mg/kg治疗.实验结束后处死大鼠取血管内皮组织制备病理标本,免疫荧光染色检测内皮细胞NF-κB的表达,TUNEL法检测内皮细胞凋亡情况,Western-blot法测定并比较内皮细胞Caspase-3等凋亡蛋白表达情况.结果 荧光显微镜下观察,脓毒症组和丹参酮ⅡA干预组血管内皮细胞浆和细胞核均显示不同程度的红色颗粒染色,脓毒症组血管内皮细胞中NF-κB平均光密度值明显高于对照组(t/P=213.158/0.000),丹参酮ⅡA干预组NF-κB平均光密度值明显低于脓毒症组(t/P=116.995/0.000).与对照组比较,脓毒症组内皮细胞出现典型的细胞凋亡形态,胞核固缩,致密深染,染色质边集,细胞质内可见亮蓝色强荧光;与脓毒症组比较,丹参酮ⅡA干预组细胞凋亡程度减轻.与对照组比较,脓毒症组血管内皮细胞Caspase-3表达水平明显增加(t/P=20.086/0.000),与脓毒症组比较,丹参酮ⅡA干预组血管内皮细胞Caspase-3表达水平明显降低(t/P=24.576/0.000).结论 丹参酮ⅡA对脓毒症大鼠血管内皮细胞具有保护作用,可能与抑制NF-κB信号传导通路进而降低内皮细胞凋亡有关.

BACKGROUND:Until now, no antiviral treatment has been proven to be effective for the coronavirus disease 2019 (COVID-19). The timing of oxygen therapy was considered to have a great influence on the symptomatic relief of hypoxemia and seeking medical intervention, especially in situations with insufficient medical resources, but the evidence on the timing of oxygen therapy is limited.METHODS AND FINDINGS:Medical charts review was carried out to collect the data of hospitalized patients with COVID-19 infection confirmed in Tongji hospital, Wuhan from 30th December 2019 to 8th March 2020. In this study, the appropriate timing of oxygen therapy and risk factors associated with severe and fatal illness were identified and the effectiveness of antivirus on disease progression was assessed. Among 1362 patients, the prevalence of hypoxia symptoms was significantly higher in those patients with severe and fatal illness than in those with less severe disease. The onset of hypoxia symptoms was most common in the second to third week after symptom onset, and patients with critical and fatal illness experienced these symptoms earlier than those with mild and severe illness. In multivariable analyses, the risk of death increased significantly when oxygen therapy was started more than 2 days after hypoxia symptoms onset among critical patients (OR, 1.92; 95%CI, 1.20 to 3.10). Compared to the critically ill patients without IFN-a, the patients who were treated with IFN-a had a lower mortality (OR, 0.60; 95%CI, 0.39 to 0.91).CONCLUSIONS:Early initiation of oxygen therapy was associated with lower mortality among critical patients. This study highlighted the importance of early oxygen therapy after the onset of hypoxia symptoms. Our results also lend support to potentially beneficial effects of IFNα on critical illness.

目的:探讨丹参酮ⅡA对心肌成纤维细胞损伤的保护作用及可能机制.方法:分离和培养大鼠心肌成纤维细胞(Cardiac Fibroblast,CFs).以脂多糖(LPS)刺激CFs建立脓毒症心肌损伤体外模型,以不同浓度丹参酮ⅡA预处理CFs 30 min后,给予LPS刺激,设对照组,LPS模型组,LPS+不同浓度TSA(2μmol/L、10μmol/L、50μmol/L)组;采用蛋白质免疫印迹试验法(Western blotting)检测CFs的NLRP3和Caspase-1蛋白表达水平,酶联免疫吸附试验(ELISA)检测细胞上清中IL-1β和IL-18的含量.结果:LPS刺激24 h后,CFs的NLRP3蛋白的表达水平最高.LPS模型组NLRP3和Caspase-1蛋白的表达较对照组明显升高(P<0.01).与LPS模型组比较,丹参酮ⅡA(10μmol/L、50μmol/L)处理组NLRP3和Caspase-1蛋白的表达均明显降低(P<0.05);丹参酮ⅡA处理组的IL-1β和IL-18水平均明显低于LPS模型组(P<0.05).结论:丹参酮ⅡA能抑制LPS诱导的心肌成纤维细胞内NLRP3/Caspase-1炎症反应信号通路分子的表达,这可能是其保护心肌细胞的分子机制之一.

Introduction: Respiratory viruses can directly or indirectly damage the pulmonary defense barrier, potentially contributing to acute respiratory distress syndrome (ARDS). Despite developments in the understanding of the pathogenesis of ARDS, the underlying pathophysiology still needs to be elucidated. Areas covered: The PubMed database was reviewed for relevant papers published up to 2021. This review summarizes the currently immunological and clinical studies to provide a systemic overview of the epithelial-endothelial barrier, given the recently published immunological profiles upon viral pneumonia, and the potentially detrimental contribution to respiratory function caused by damage to this barrier. Expert opinion: The biophysical structure of host pulmonary defense is intrinsically linked with the ability of alveolar epithelial and capillary endothelial cells, known as the epithelial-endothelial barrier, to respond to, and instruct the delicate immune system to protect the lungs from infections and injuries. Recently published immunological profiles upon viral infection, and its contributions to the damage of respiratory function, suggest a central role for the pulmonary epithelial and endothelial barrier in the pathogenesis of ARDS. We suggest a central role and common pathways by which the epithelial-endothelial barrier contributes to the pathogenesis of ARDS.

BACKGROUND:Coronavirus disease 2019 (COVID-19) is still a pandemic, with a high mortality rate in severe/critical cases. Therapies based on the Shenghuang Granule have proved helpful in viral infection and septic shock.HYPOTHESIS/PURPOSE:The objective of the current study was to compare the efficacy and safety of the traditional Chinese medicine, Shenhuang Granule, with standard care in hospitalized patients with severe/critical COVID-19.STUDY DESIGN AND METHODS:This was an open-label, multicenter, randomized, controlled clinical trial. At 4 medical centers, a total of 111 severe/critical patients were randomly assigned to receive Shenhuang Granule (SHG group) twice a day for 14 days, in addition to standard care, or to receive standard care alone (Control group). The maximal follow up time was 75 days. The clinical endpoint was clinical improvement and mortality.RESULTS:54 patients were assigned to the control group and 57 to the SHG group. The overall mortality was 75.9% (41/54) in the control group, and 38.6% (22/57) in the SHG group (p < 0.01 vs. control). The post hoc analysis showed that in the severe category, the mortality of the control group vs. the SHG group was 58.8% (10/17) vs. 5.3% (1/19) (p < 0.01); while in the critical category, it was 83.8% (31/37) vs. 55.3% (21/38) (p < 0.05). In the severe category, the mortality of patients who eventually received an invasive ventilator in the control vs. the SHG group was 58.8% (10/17) vs. 0 (0/19) (p < 0.01). Administration of SHG was associated with increased lymphocytes and decreased adverse events.CONCLUSION:Shenhuang Granule is a promising integrative therapy for severe and critical COVID-19.

Introduction Tanshinone IIa (TSA) has been approved to treat cardiovascular diseases by the China State Food and Drug Administration. TSA has exhibited a variety of pharmacological effects, including vasodilator, antioxidant, anti-inflammatory, and anti-tumor properties. Endothelial cells play an important physiological role in vascular homeostasis and control inflammation, coagulation, and thrombosis. Accumulating studies have shown that TSA can improve endothelial function through various pathways. Areas covered The PubMed database was reviewed for relevant papers published up to 2020. This review summarizes the current clinical and pharmaceutical studies to provide a systemic overview of the pharmacological and therapeutic effects of TSA on endothelial cells. Expert opinion TSA is a representative monomeric compound extracted from Danshen and it exhibits significant pharmacological and therapeutic properties to improve endothelial cell function, including alleviating oxidative stress, attenuating inflammatory injury, modulating ion channels and so on. TSA represents a spectrum of agents that are extracted from plants and can restore the endothelial function to establish the beneficial and harmless molecular therapeutics. This also suggests the possible detection of endothelial cells for very early diagnosis of diseases. In future, precise therapeutic methods will be developed to repair endothelial cells injury and recover endothelial dysfunction.

Currently, little in-depth evidence is known about the application of extracorporeal membrane oxygenation (ECMO) therapy in coronavirus disease 2019 (COVID-19) patients. This retrospective multicenter cohort study included patients with COVID-19 at 7 designated hospitals in Wuhan, China. The patients were followed up until June 30, 2020. Univariate and multivariate logistic regression analyses were performed to identify the risk factors associated with unsuccessful ECMO weaning. Propensity score matching was used to match patients who received veno-venous ECMO with those who received invasive mechanical ventilation (IMV)-only therapy. Of 88 patients receiving ECMO therapy, 27 and 61 patients were and were not successfully weaned from ECMO, respectively. Additionally, 15, 15, and 65 patients were further weaned from IMV, discharged from hospital, or died during hospitalization, respectively. In the multivariate logistic regression analysis, a lymphocyte count ≤0.5×109/L and D-dimer concentration >4× the upper limit of normal level at ICU admission, a peak PaCO2 >60 mmHg at 24 h before ECMO initiation, and no tracheotomy performed during the ICU stay were independently associated with lower odds of ECMO weaning. In the propensity score-matched analysis, a mixed-effect Cox model detected a lower hazard ratio for 120-day all-cause mortality after ICU admission during hospitalization in the ECMO group. The presence of lymphocytopenia, higher D-dimer concentrations at ICU admission and hypercapnia before ECMO initiation could help to identify patients with a poor prognosis. Tracheotomy could facilitate weaning from ECMO. ECMO relative to IMV-only therapy was associated with improved outcomes in critically ill COVID-19 patients.

Background: Ever since the COVID-19 pneumonia emerged in Wuhan, China, in December 2019, it has rapidly spread worldwide, resulting in high mortality. This study aimed to delineate the clinical characteristics of critically ill patients with COVID-19 infection in the intensive care unit. Methods: In this retrospective study, the clinical characteristics of 88 critically ill patients with COVID-19 infection were collected. Analysis among three subgroups, classified according to the survival time, was performed. Results: The median age was 70.7(62.3-78.25) years of critical ill patients. Hypertension (43.2%) was the most frequent underlying disease. At the time of admission, compared to other patients, patients of the≤7 days category showed greater impairment of consciousness, as per the Glasgow Coma Scale (GCS) scores(11.0±2.9, P<0.01). The lymphocyte percentages in all patients (4.1 ± 0.78) were much lower than the normal values. Particularly, acute kidney failure occurred more frequently in patients of the ≤7 days category (45.2%, P<0.01). The time distributions of the mortality rates were 31deaths in ≤7 days, 33 deaths in 8–14days, and7 deaths in >14days (P=0.01). Conclusion: Critically ill patients with COVID-19 infection showed high risk of mortality. The primary immune response of lymphocytes against the COVID-19 infection was severely destroyed. Higher GCS score predicted greater possibility of survival. However, acute kidney injury may be an indicator of worse outcome.

Background The coronavirus disease 2019 (COVID-19) pandemic has led to surges in the demand for extracorporeal membrane oxygenation (ECMO) therapy. However, little in-depth evidence is known about the application of ECMO therapy in COVID-19 patients. Methods This retrospective multicenter cohort study included 88 patients who had been diagnosed with COVID-19 and received ECMO therapy at seven designated hospitals in Wuhan, China. The clinical characteristics, laboratory examinations, treatments, and outcomes were extracted from electronic medical records and compared between weaned and non-weaned ECMO patients. The patients were followed until June 30, 2020. Logistic regression analyses were performed to identify the risk factors associated with unsuccessful ECMO weaning. Propensity score matching was used to match patients who received veno-venous ECMO with those who received invasive mechanical ventilation (IMV)-only therapy. The primary endpoint, 120-day all-cause mortality after intensive care unit (ICU) admission during hospitalization, was compared using a mixed-effect Cox model. Results Of 88 patients who received ECMO therapy, 27 and 61 patients were and were not successfully weaned from ECMO, respectively. Additionally, 15, 15, and 65 patients were further weaned from IMV, discharged from hospital, or died during hospitalization, respectively. A lymphocyte count ≤ 0.5 × 109/L and D-dimer concentration > 4 × the upper limit of normal at ICU admission, a peak PaCO2 > 60 mmHg at 24 hours before ECMO initiation, and no tracheotomy performed during the ICU stay were independently associated with lower odds of ECMO weaning. In the propensity score-matched analysis, a mixed-effect Cox model detected a lower hazard ratio for 120-day all-cause mortality after ICU admission during hospitalization in the ECMO group, as compared with the IMV-only group. Conclusion Patients in Wuhan who received ECMO therapy had a relatively high mortality rate. This outcome may be largely attributable to resource-limited situations during the COVID-19 outbreak. In future, the presence of lymphocytopenia and higher D-dimer concentrations at ICU admission and hypercapnia at 24 hours before ECMO initiation could help to identify patients with a poor prognosis. Moreover, tracheotomy could facilitate weaning from ECMO. Despite the high mortality, ECMO was associated with improved outcomes relative to IMV-only therapy in critically ill COVID-19 patients.

目的 观察丹参酮ⅡA磺酸钠对大鼠肠缺血再灌注(Ⅱ/R)肺损伤的作用及影响机制.方法 2019年1—12月于华中科技大学同济医学院附属同济医院进行实验.将30只健康雄性SD大鼠随机数字表法分为假手术+NS组(Sham组),肠缺血再灌注+NS组(Ⅱ/R组),肠缺血再灌注+丹参酮ⅡA磺酸钠注射液组(TanshinoneⅡA组),每组10只.实验结束后处死大鼠取肺组织及支气管肺泡灌洗液(BALF)标本,观察大鼠肺组织病理学改变;测定各组大鼠肺组织湿/干比(W/D);检测大鼠动脉血PaO2,BALF蛋白浓度及炎性细胞因子IL-1β、IL-6及TNF-α水平;检测大鼠肺组织TLR4及pNF-κB p65蛋白表达.结果 肺组织损伤评分、W/D值比较,Sham组<TanshinoneⅡA组<Ⅱ/R组(F/P=178.368/0.000、223.028/0.000);动脉血PaO2比较,Sham组>TanshinoneⅡA组>Ⅱ/R组(F/P=190.446/0.000);BALF蛋白浓度及BALF炎性细胞因子IL-1β、IL-6及TNF-α水平比较,Sham组<TanshinoneⅡA组<Ⅱ/R组(F/P=450.405/0.000、234.850/0.000、1679.317/0.000、543.886/0.000);肺组织TLR4及pNF-κB p65蛋白表达比较,Sham组<TanshinoneⅡA组<Ⅱ/R组(F/P=1434.247/0.000、334.075/0.000).结论 丹参酮ⅡA磺酸钠对Ⅱ/R所致肺损伤具有明显的保护作用,其保护作用可能与抑制TLR4/NF-κB的活化进而抑制肺部炎性反应有关.

Coronavirus Disease 2019 (COVID-19) was first identified in China at the end of 2019. Acute respiratory distress syndrome (ARDS) represents the most common and serious complication of COVID-19. Cytokine storms are a pathophysiological feature of COVID-19 and play an important role in distinguishing hyper-inflammatory subphenotypes of ARDS. Accordingly, in this review, we focus on hyper-inflammatory host responses in ARDS that play a critical role in the differentiated development of COVID-19. Furthermore, we discuss inflammation-related indicators that have the potential to identify hyper-inflammatory subphenotypes of COVID-19, especially for those with a high risk of ARDS. Finally, we explore the possibility of improving the quality of monitoring and treatment of COVID-19 patients and in reducing the incidence of critical illness and mortality via better distinguishing hyper- and hypo-inflammatory subphenotypes of COVID-19.