Effects of tidal volume on physiology and clinical outcomes in patients with one­lung ventilation undergoing surgery: A meta­analysis of randomized controlled trials.

There is no detailed study on how tidal volume (VT) affects patients during one-lung ventilation (OLV). The present study conducted a meta-analysis to assess the effect of VT on physiology and clinical outcomes in OLV patients. Databases until February 2023 were retrieved from PubMed, Cochrane Library and Web of Science. Randomized controlled trials comparing the application of low and high VT ventilation in adults with OLV were performed. Demographic variables, VT, physiology, and clinical outcomes were retrieved. The random-effects model calculated the summary of odds ratios with 95% confidence intervals (CI) and mean difference with standard deviation. A total of 12 studies involving a total of 876 participants met the inclusion criteria. Low VT ventilation was associated with decreased risk of acute lung injury [relative risk 0.50, 95% CI (0.28, 0.88), P=0.02]. Low VT ventilation decreased the driving pressure (ΔP) and peak pressure (Ppeak) and improved arterial oxygen pressure (PaO2)/fraction of inspired oxygen (FiO2). Furthermore, the present study suggested that a significant difference in blood IL-6 was observed between low and high VT ventilation [mean difference, -35.51 pg/ml, 95% CI (-66.47, -4.54 pg/ml), P=0.02]. A decrease in the length of stay at the hospital occurred in the low VT group when set to 4-5 ml/kg. In the OLV patients, low VT ventilation decreased the risk of acute lung injury, blood IL-6, ΔP and Ppeak, and improved PaO2/FiO2. Furthermore, when low VT was set to 4-5 ml/kg, the length of stay at the hospital decreased.

Fast gelling, high performance MXene hydrogels for wearable sensors.

Hydrogel-based functional materials had attracted great attention in the fields of artificial intelligence, soft robotics, and motion monitoring. However, the gelation of hydrogels induced by free radical polymerization typically required heating, light exposure, and other conditions, limiting their practical applications and development in real-life scenarios. In this study, a simple and direct method was proposed to achieve rapid gelation at room temperature by incorporating reductive MXene sheets in conjunction with metal ions into the chitosan network and inducing the formation of a polyacrylamide network in an extremely short time (10 s). This resulted in a dual-network MXene-crosslinked conductive hydrogel composite that exhibited exceptional stretchability (1350 %), remarkably low dissipated energy (0.40 kJ m-3 at 100 % strain), high sensitivity (GF = 2.86 at 300-500 % strain), and strong adhesion to various substrate surfaces. The study demonstrated potential applications in the reliable detection of various motions, including repetitive fine movements and large-scale human body motions. This work provided a feasible platform for developing integrated wearable health-monitoring electronic systems.

Development of genomic phenotype and immunophenotype of acute respiratory distress syndrome using autophagy and metabolism-related genes.

Background: Distinguishing ARDS phenotypes is of great importance for its precise treatment. In the study, we attempted to ascertain its phenotypes based on metabolic and autophagy-related genes and infiltrated immune cells. Methods: Transcription datasets of ARDS patients were obtained from Gene expression omnibus (GEO), autophagy and metabolic-related genes were from the Human Autophagy Database and the GeneCards Database, respectively. Autophagy and metabolism-related differentially expressed genes (AMRDEGs) were further identified by machine learning and processed for constructing the nomogram and the risk prediction model. Functional enrichment analyses of differentially expressed genes were performed between high- and low-risk groups. According to the protein-protein interaction network, these hub genes closely linked to increased risk of ARDS were identified with CytoHubba. ssGSEA and CIBERSORT was applied to analyze the infiltration pattern of immune cells in ARDS. Afterwards, immunologically characterized and molecular phenotypes were constructed according to infiltrated immune cells and hub genes. Results: A total of 26 AMRDEGs were obtained, and CTSB and EEF2 were identified as crucial AMRDEGs. The predictive capability of the risk score, calculated based on the expression levels of CTSB and EEF2, was robust for ARDS in both the discovery cohort (AUC = 1) and the validation cohort (AUC = 0.826). The mean risk score was determined to be 2.231332, and based on this score, patients were classified into high-risk and low-risk groups. 371 differential genes in high- and low-risk groups were analyzed. ITGAM, TYROBP, ITGB2, SPI1, PLEK, FGR, MPO, S100A12, HCK, and MYC were identified as hub genes. A total of 12 infiltrated immune cells were differentially expressed and have correlations with hub genes. According to hub genes and implanted immune cells, ARDS patients were divided into two different molecular phenotypes (Group 1: n = 38; Group 2: n = 19) and two immune phenotypes (Cluster1: n = 22; Cluster2: n = 35), respectively. Conclusion: This study picked up hub genes of ARDS related to autophagy and metabolism and clustered ARDS patients into different molecular phenotypes and immunophenotypes, providing insights into the precision medicine of treating patients with ARDS.

Quantitative evaluation of myocardial layer-specific strain using two-dimensional speckle tracking echocardiography in septic patients.

BACKGROUND: Although global longitudinal strain (GLS) is proven to be reduced and associated with adverse outcomes in septic patients, it has not been elucidated whether or not layer-specific strains are reduced. We aimed to explore the layer-specific strains of left ventricular (LV) for assessing myocardial dysfunction in septic patients. METHODS: A prospective observational study of patients with sepsis was conducted in a tertiary hospital in China. Routine two-dimensional speckle tracking echocardiography was performed within 24 h of enrollment. Demographic data, laboratory values, and clinical outcomes were collected. RESULTS: We recruited 79 septic patients finally. The mean age of septic patients was 59.4 years old and 45 (57.0%) were male. The median Acute Physiology Age and Chronic Health Evaluation (APACHE II) score, and mean sequential organ failure assessment (SOFA) score of all patients were 19.0 and 7.7, respectively. According to the left ventricular ejection fraction (LVEF) value of 50%, the patients were categorized into two groups: SICM (sepsis-induced cardiomyopathy, LVEF < 50%, n = 22) and non-SICM group ( LVEF ≥ 50%, n = 57). The median LVEF of SICM and non-SICM patients were 41.9% and 58.7%, and SICM patients had less negative layer-specific strain and global strain than that of non-SICM patients. The echocardiographic comparison of non-SICM and healthy controls was conducted to explore the myocardial injuries of non-SICM patients and the non-SICM had worse LS-epi than that of controls (-18.5% vs. -21.4%, p = 0.024). CONCLUSION: There were 72.2% (57) septic patients presented with non-SICM (LVEF ≥ 50%), and the strain value of epicardium of them was less negative than healthy controls.

Activation of Wnt/ß­Catenin­p130/E2F4 promotes the differentiation of bone marrow­derived mesenchymal stem cells into type II alveolar epithelial cells through cell cycle arrest.

The results of our previous study demonstrated that activation of the Wnt/ß-catenin pathway increased the differentiation of mesenchymal stem cells (MSCs) into type II alveolar epithelial (AT II) cells; however, the specific mechanisms remain unclear. The present study aimed to evaluate the role of Wnt/ß-catenin-p130/E2F transcription factor 4 (E2F4) in regulating the differentiation of mouse MSCs (mMSCs) into AT II cells, and to determine the specific mechanisms. mMSCs with p130 or E2F4 overexpression were constructed using lentiviral vectors. Differentiation of mMSCs into AT II cells was promoted using a modified coculture system with murine lung epithelial-12 cells incubated in small airway growth medium for 7-14 days. The differentiation efficiency was detected using immunofluorescence, western blot analysis and transmission electron microscopy. To detect the association between the canonical Wnt pathway and p130/E2F4, 4 mmol/l lithium chloride (LiCl) or 200 ng/ml Dickkopf-related protein 1 (DKK-1) was also added to the coculture system. Following differentiation, the cell cycle of mMSCs was evaluated using flow cytometry. The results of the present study demonstrated that surfactant protein C (SP-C) protein expression was higher in the p130 overexpression (MSC-p130) and E2F4 overexpression (MSC-E2F4) groups compared with the normal control mMSCs group following differentiation into AT II cells. Similar results for SP-C protein expression and lamellar body-like structures were also observed using immunofluorescence analysis and electron microscopy. Following the addition of LiCl into the coculture system for activation of the Wnt/ß-catenin signaling pathway, phosphorylated (p)-p130/p130 was slightly decreased at 7 days and E2F4 was increased both at 7 and 14 days in mMSCs. Furthermore, the p-p130/p130 ratio was significantly increased at 14 days and E2F4 was decreased both at 7 and 14 days following DKK-1-mediated inhibition of the Wnt pathway. The results of the present study demonstrated that the numbers of cells in G1 and S phases were increased following activation of the Wnt pathway and decreased following Wnt pathway inhibition. However, the number of cells in G1 phase was increased following the differentiation of mMSCs overexpressing p130 or E2F4. Therefore, the results of the present study revealed that the canonical Wnt signaling pathway may affect the differentiation of MSCs into AT II cells via regulation of downstream p130/E2F4. The specific mechanisms may be associated with G1 phase extension in the cell cycle of MSCs.

Extracellular Histone-Induced Protein Kinase C Alpha Activation and Troponin Phosphorylation Is a Potential Mechanism of Cardiac Contractility Depression in Sepsis.

Reduction in cardiac contractility is common in severe sepsis. However, the pathological mechanism is still not fully understood. Recently it has been found that circulating histones released after extensive immune cell death play important roles in multiple organ injury and disfunction, particularly in cardiomyocyte injury and contractility reduction. How extracellular histones cause cardiac contractility depression is still not fully clear. In this work, using cultured cardiomyocytes and a histone infusion mouse model, we demonstrate that clinically relevant histone concentrations cause significant increases in intracellular calcium concentrations with subsequent activation and enriched localization of calcium-dependent protein kinase C (PKC) α and ßII into the myofilament fraction of cardiomyocytes in vitro and in vivo. Furthermore, histones induced dose-dependent phosphorylation of cardiac troponin I (cTnI) at the PKC-regulated phosphorylation residues (S43 and T144) in cultured cardiomyocytes, which was also confirmed in murine cardiomyocytes following intravenous histone injection. Specific inhibitors against PKCα and PKCßII revealed that histone-induced cTnI phosphorylation was mainly mediated by PKCα activation, but not PKCßII. Blocking PKCα also significantly abrogated histone-induced deterioration in peak shortening, duration and the velocity of shortening, and re-lengthening of cardiomyocyte contractility. These in vitro and in vivo findings collectively indicate a potential mechanism of histone-induced cardiomyocyte dysfunction driven by PKCα activation with subsequent enhanced phosphorylation of cTnI. These findings also indicate a potential mechanism of clinical cardiac dysfunction in sepsis and other critical illnesses with high levels of circulating histones, which holds the potential translational benefit to these patients by targeting circulating histones and downstream pathways.

Clinical outcome and risk factors for acute fulminant myocarditis supported by venoarterial extracorporeal membrane oxygenation: An analysis of nationwide CSECLS database in China.

BACKGROUND: To assess the outcomes and risk factors for adult patients with acute fulminant myocarditis (AFM) supported with venoarterial extracorporeal membrane oxygenation (VA ECMO) in China mainland. METHODS: Data were extracted from Chinese Society of ExtraCorporeal Life Support (CSECLS) Registry database. Data from adult patients who were diagnosed with AFM and needed VA ECMO in the database were retrospectively analyzed. The primary outcome was 90-day mortality after ECMO initiation in patients with AFM supported with VA ECMO. Cox proportional hazard regression model was used to examine the risk factors associated with 90-day mortality. RESULTS: Among 221 patients enrolled and followed up to 90 days, 186 (84.2%) patients weaned from ECMO and 159 (71.9%) patients survived and discharged home. The median age was 38 years (IQR 29-49) and males (n = 115) represented 52.0% of the total accounted patients. The median ECMO duration was 134 h (IQR 96-177 h). The main adverse event during ECMO course was bleeding (16.3%), followed by infection (15.4%). In the multivariate Cox model analysis, cardiac arrest prior to ECMO initiation (adjusted HR 2.529; 95%CI: 1.341-4.767, p = 0.004), lower pH value (adjusted HR 0.016; 95%CI: 0.010-0.059, p < 0.001) and higher lactate concentration at 24 h after ECMO initiation (adjusted HR 1.146; 95%CI: 1.075-1.221, p < 0.001) were associated with 90-day mortality. CONCLUSIONS: 71.9% patients with AFM (clinical diagnosed) supported with VA ECMO survived. Cardiac arrest prior to ECMO, lower pH and higher lactate concentration at 24 h after ECMO initiation were correlated with 90-day mortality of AFM patients supported with VA ECMO.

Early decrease of ventilatory ratio after prone position ventilation may predict successful weaning in patients with acute respiratory distress syndrome: A retrospective cohort study.

Background: Previous studies usually identified patients who benefit the most from prone positioning by oxygenation improvement. However, inconsistent results have been reported. Physiologically, pulmonary dead space fraction may be more appropriate in evaluating the prone response. As an easily calculated bedside index, ventilatory ratio (VR) correlates well with pulmonary dead space fraction. Hence, we investigated whether the change in VR after prone positioning is associated with weaning outcomes at day 28 and to identify patients who will benefit the most from prone positioning. Materials and methods: This retrospective cohort study was performed in a group of mechanically ventilated, non-COVID ARDS patients who received prone positioning in the ICU at Zhongda hospital, Southeast University. The primary outcome was the rate of successful weaning patients at day 28. Arterial blood gas results and corresponding ventilatory parameters on five different time points around the first prone positioning were collected, retrospectively. VR responders were identified by Youden's index. Competing-risk regression models were used to identify the association between the VR change and liberation from mechanical ventilation at day 28. Results: One hundred and three ARDS patients receiving prone positioning were included, of whom 53 (51%) successfully weaned from the ventilator at day 28. VR responders were defined as patients showing a decrease in VR of greater than or equal to 0.037 from the baseline to within 4 h after prone. VR responders have significant longer ventilator-free days, higher successful weaning rates and lower mortality compared with non-responders at day 28. And a significant between-group difference exists in the respiratory mechanics improvement after prone (P < 0.05). A linear relationship was also found between VR change and compliance of the respiratory system (Crs) change after prone (r = 0.32, P = 0.025). In the multivariable competing-risk analysis, VR change (sHR 0.57; 95% CI, 0.35-0.92) was independently associated with liberation from mechanical ventilation at day 28. Conclusion: Ventilatory ratio decreased more significantly within 4 h after prone positioning in patients with successful weaning at day 28. VR change was independently associated with liberation from mechanical ventilation at day 28.

Longitudinal phenotypes in patients with acute respiratory distress syndrome: a multi-database study.

BACKGROUND: Previously identified phenotypes of acute respiratory distress syndrome (ARDS) have been limited by a disregard for temporal dynamics. We aimed to identify longitudinal phenotypes in ARDS to test the prognostic and predictive enrichment of longitudinal phenotypes, and to develop simplified models for phenotype identification. METHODS: We conducted a multi-database study based on the Chinese Database in Intensive Care (CDIC) and four ARDS randomized clinical trials (RCTs). We employed latent class analysis (LCA) to identify longitudinal phenotypes using 24-hourly data from the first four days of invasive ventilation. We used the Cox regression model to explore the association between time-varying respiratory parameters and 28-day mortality across phenotypes. Phenotypes were validated in four RCTs, and the heterogeneity of treatment effect (HTE) was investigated. We also constructed two multinomial logistical regression analyses to develop the probabilistic models. FINDINGS: A total of 605 ARDS patients in CDIC were enrolled. The three-class LCA model was identified and had the optimal fit, as follows: Class 1 (n = 400, 66.1% of the cohort) was the largest phenotype over all study days, and had fewer abnormal values, less organ dysfunction and the lowest 28-day mortality rate (30.5%). Class 2 (n = 102, 16.9% of the cohort) was characterized by pulmonary mechanical dysfunction and had the highest proportion of poorly aerated lung volume, the 28-day mortality rate was 47.1%. Class 3 (n = 103, 17% of the cohort) was correlated with extra-pulmonary dysfunction and had the highest 28-day mortality rate (56.3%). Time-varying mechanical power was more significantly associated with 28-day mortality in Class 2 patients compared to other phenotypes. Similar phenotypes were identified in four RCTs. A significant HTE between phenotypes and treatment strategies was observed in the ALVEOLI (high PEEP vs. low PEEP) and the FACTT trials (conservative vs. liberal fluid management). Two parsimonious probabilistic models were constructed to identify longitudinal phenotypes. INTERPRETATION: We identified and validated three novel longitudinal phenotypes for ARDS patients, with both prognostic and predictive enrichment. The phenotypes of ARDS can be accurately identified with simple classifier models, except for Class 3.

Hepatocyte growth factor protects pulmonary endothelial barrier against oxidative stress and mitochondria-dependent apoptosis.

BACKGROUND: Pulmonary microvascular endothelial cells (PMVECs) were not complex, and the endothelial barrier was destroyed in the pathogenesis progress of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Previous studies have demonstrated that hepatocyte growth factor (HGF), which was secreted by bone marrow mesenchymal stem cells, could decrease endothelial apoptosis. We investigated whether mTOR/STAT3 signaling acted in HGF protective effects against oxidative stress and mitochondria-dependent apoptosis in lipopolysaccharide (LPS)-induced endothelial barrier dysfunction and ALI mice. METHODS: In our current study, we introduced LPS-induced PMEVCs with HGF treatment. To investigate the effects of mammalian target of rapamycin (mTOR)/signal transducer and activator of transcription 3 (STAT3) pathway in endothelial oxidative stress and mitochondria-dependent apoptosis, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 were, respectively, used to inhibit mTOR/STAT3 signaling. Moreover, lentivirus vector-mediated mTORC1 (Raptor) and mTORC2 (Rictor) gene knockdown modifications were introduced to evaluate mTORC1 and mTORC1 pathways. Calcium measurement, reactive oxygen species (ROS) production, mitochondrial membrane potential and protein, cell proliferation, apoptosis, and endothelial junction protein were detected to evaluate HGF effects. Moreover, we used the ALI mouse model to observe the mitochondria pathological changes with an electron microscope in vivo. RESULTS: Our study demonstrated that HGF protected the endothelium via the suppression of ROS production and intracellular calcium uptake, which lead to increased mitochondrial membrane potential (JC-1 and mitochondria tracker green detection) and specific proteins (complex I), raised anti-apoptosis Messenger Ribonucleic Acid level (B-cell lymphoma 2 and Bcl-xL), and increased endothelial junction proteins (VE-cadherin and occludin). Reversely, mTOR inhibitor rapamycin and STAT3 inhibitor S3I-201 could raise oxidative stress and mitochondria-dependent apoptosis even with HGF treatment in LPS-induced endothelial cells. Similarly, mTORC1 as well as mTORC2 have the same protective effects in mitochondria damage and apoptosis. In in vivo experiments of ALI mouse, HGF also increased mitochondria structural integrity via the mTOR/STAT3 pathway. CONCLUSION: In all, these reveal that mTOR/STAT3 signaling mediates the HGF suppression effects to oxidative level, mitochondria-dependent apoptosis, and endothelial junction protein in ARDS, contributing to the pulmonary endothelial survival and barrier integrity.

Sustainable power generation for at least one month from ambient humidity using unique nanofluidic diode.

The continuous energy-harvesting in moisture environment is attractive for the development of clean energy source. Controlling the transport of ionized mobile charge in intelligent nanoporous membrane systems is a promising strategy to develop the moisture-enabled electric generator. However, existing designs still suffer from low output power density. Moreover, these devices can only produce short-term (mostly a few seconds or a few hours, rarely for a few days) voltage and current output in the ambient environment. Here, we show an ionic diode-type hybrid membrane capable of continuously generating energy in the ambient environment. The built-in electric field of the nanofluidic diode-type PN junction helps the selective ions separation and the steady-state one-way ion charge transfer. This directional ion migration is further converted to electron transportation at the surface of electrodes via oxidation-reduction reaction and charge adsorption, thus resulting in a continuous voltage and current with high energy conversion efficiency.

Isolation of Primary Mouse Pulmonary Microvascular Endothelial Cells and Generation of an Immortalized Cell Line to Obtain Sufficient Extracellular Vesicles.

Pulmonary microvascular endothelial cells (PMECs) and the extracellular vesicles (EVs) derived from PMECs participate in maintaining pulmonary homeostasis and mediating the inflammatory response. However, obtaining a high-purity population of PMECs and their EVs from mouse is still notoriously difficult. Herein we provide a method to isolate primary mouse PMECs (pMPMECs) and to transduce SV40 lentivirus into pMPMECs to establish an immortalized cell line (iMPMECs), which provides sufficient quantities of EVs for further studies. pMPMECs and iMPMECs can be identified using morphologic criteria, a phenotypic expression profile (e.g., CD31, CD144, G. simplicifolia lectin binding), and functional properties (e.g., Dil-acetylated low-density protein uptake, Matrigel angiogenesis). Furthermore, pMPMEC-EVs and iMPMEC-EVs can be identified and compared. The characteristics of pMPMEC-EVs and iMPMEC-EVs are ascertained by transmission electron microscopy, nanoparticle tracking analysis, and specific protein markers. iMPMECs produce far more EVs than pMPMECs, while their particle size distribution is similar. Our detailed protocol to isolate and immortalize MPMECs will provide researchers with an in vitro model to investigate the specific roles of EVs in pulmonary physiology and diseases.

Association of Frailty With the Risk of Mortality and Resource Utilization in Elderly Patients in Intensive Care Units: A Meta-Analysis.

Background: The associations of frailty with the risk of mortality and resource utilization in the elderly patients admitted to intensive care unit (ICU) remain unclear. To address these issues, we performed a meta-analysis to determine whether frailty is associated with adverse outcomes and increased resource utilization in elderly patients admitted to the ICU. Methods: We searched PubMed, EMBASE, ScienceDirect, and Cochrane Central Register of Controlled Trials through August 2021 to identify the relevant studies that investigated frailty in elderly (≥ 65 years old) patients admitted to an ICU and compared outcomes and resource utilization between frail and non-frail patients. The primary outcome was mortality. We also investigated the prevalence of frailty and the impact of frailty on the health resource utilization, such as hospital length of stay (LOS) and resource utilization of ICU. Results: A total of 13 observational studies enrolling 64,279 participants (28,951 frail and 35,328 non-frail) were finally included. Frailty was associated with an increased risk of short-term mortality (10 studies, relative risk [RR]: 1.70; 95% CI: 1.45-1.98), in-hospital mortality (five studies, RR: 1.73; 95% CI: 1.55-1.93), and long-term mortality (six studies, RR: 1.86; 95% CI: 1.44-2.42). Subgroup analysis showed that retrospective studies identified a stronger correlation between frailty and hospital LOS (three studies, MD 1.14 d; 95% CI: 0.92-1.36). Conclusions: Frailty is common in the elderly patients admitted to ICU, and is associated with increased mortality and prolonged hospital LOS. Trial registration: This study was registered in the PROSPERO database (CRD42020207242).

mTORC2 Activation Mediated by Mesenchymal Stem Cell-Secreted Hepatocyte Growth Factors for the Recovery of Lipopolysaccharide-Induced Vascular Endothelial Barrier.

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is characterized by pulmonary microvascular endothelial barrier dysfunction. Mesenchymal stem cell-secreted hepatocyte growth factor (HGF) has positive effects of lipopolysaccharide- (LPS-) induced pulmonary endothelial barrier. Studies have exhibited the mammalian TORC1 (mTORC1) signaling is of potent angiogenesis effects. The mTOR protein kinase has two distinct multiprotein complexes mTORC1 and mTORC2 that regulate different branches of the mTOR network. However, detailed mTORC2 mechanisms of HGF protective effects remain poorly defined. Therefore, the aim of this study was to determine whether mTORC2 mediated protective effects of MSC-secreted HGF against LPS-induced pulmonary microvascular endothelial barrier dysfunction activated like mTORC1 activation. We introduced MSC-PMVEC coculture transwell system and recombinant murine HGF on LPS-induced endothelial cell barrier dysfunction in vitro and then explored potential mechanisms by lentivirus vector-mediated HGF, mTORC1 (raptor), and mTORC2 (rictor) gene knockdown modification. Endothelial paracellular and transcellular permeability, adherent junction protein (VE-Cadherin), cell proliferation, apoptosis, and mTOR-associated proteins were tested. These revealed that HGF could promote quick reestablishment of adherent junction VE-cadherin and decrease endothelial paracellular and transcellular permeability during LSP-induced endothelial dysfunction with the involvement of mTORC2 (rictor) and mTORC1 (raptor) pathways. Raptor and rictor knockdown in LPS-induced PMEVECs with stimulation of HGF increased apoptosis ratio, activated Cleaved-Caspase-3 expression, and downregulated cell proliferation. Moreover, mTORC2/Akt but not mTORC2/PKC had significance on HGF endothelial protective effects. Taken together, these highlight activation mTORC2 pathway could also contribute to vascular endothelial barrier recovery by MSC-secreted HGF in LPS stimulation.

Clinical characteristics and outcomes of critically ill patients with coronavirus disease 2019 with hypotension in China: a retrospective cohort study.

BACKGROUND: The characteristics of the coronavirus disease 2019 (COVID-19) patients with hypotension are still limited. We aim to describe the clinical features and outcomes of the patients. METHODS: This was a multicenter retrospective study of critically ill patients with COVID-19 from ICUs in 19 hospitals in China. All patients were followed up to day 28 or death, which came first. Clinical and outcome data were collected and analyzed. Patients were classified as early-onset or late-onset hypotension, and clinical characteristics and outcomes were compared. RESULTS: A total of 649 patients were included in the final analysis, and 240 (37.0%) were hypotension patients. The median age of hypotension patients was 67 years (IQR, 60-73 years), and 159 (66.2%) were male. 172 (71.7%) of the hypotension patients had at least one comorbidity. The 28-day mortality of the patients with hypotension was 85.4%, which was significantly higher than that of patients without hypotension. Compared with late-onset hypotension patients, the 28-day mortality of patients with early-onset hypotension was significantly higher (90.1% vs. 78.6%, P=0.02). CONCLUSIONS: Approximately one third critically ill COVID-19 patients progressed to hypotension. The mortality was significantly higher in hypotension patients than that in patients without hypotension. Compared with patients with late-onset hypotension, the mortality of patients with early-onset hypotension was significantly higher.

Nucleotide polymorphism in ARDS outcome: a whole exome sequencing association study.

BACKGROUND: Genetic locus were identified associated with acute respiratory distress syndrome (ARDS). Our goal was to explore the associations between genetic variants and ARDS outcome, as well as subphenotypes. METHODS: This was a single-center, prospective observational trial enrolling adult ARDS patients. After baseline data were collected, blood samples were drawn to perform whole exome sequencing, single nucleotide polymorphism (SNP)/insertion-deletion to explore the quantitative and functional associations between genetic variants and ICU outcome, clinical subphenotypes. Then the lung injury burden (LIB), which was defined as the ratio of nonsynonymous SNP number per megabase of DNA, was used to evaluate its value in predicting ARDS outcome. RESULTS: A total of 105 ARDS patients were enrolled in the study, including 70 survivors and 35 nonsurvivors. Based on the analysis of a total of 65,542 nonsynonymous SNP, LIB in survivors was significantly higher than nonsurvivors [1,892 (1,848-1,942)/MB versus 1,864 (1,829-1,910)/MB, P=0.018], while GO analysis showed that 60 functions were correlated with ARDS outcome, KEGG enrichment analysis showed that SNP/InDels were enriched in 13 pathways. Several new SNPs were found potentially associated with ARDS outcome. Analysis of LIB was used to determine its outcome predicting ability, the area under the ROC curve of which was only 0.6103, and increase to 0.712 when combined with APACHE II score. CONCLUSIONS: Genetic variants are associated with ARDS outcome and subphenotypes; however, their prognostic value still need to be verified by larger trials. TRIAL REGISTRATION: Clinicaltrials.gov NCT02644798. Registered 20 April 2015.

Leukocyte kinetics during the early stage acts as a prognostic marker in patients with septic shock in intensive care unit.

ABSTRACT: The leukocytes play an important role in immune function during sepsis. We performed a retrospective study to investigate if leukocytes kinetics was associated with survival in critically ill patients with septic shock in intensive care unit (ICU).Patients with septic shock from January 1, 2014 to June 30, 2018 in our ICU were included. We extracted the demographic, clinical and laboratory data, comorbidities from our clinical database. The number of white blood cell, neutrophil and lymphocyte on day 1 and day 3 after diagnosis were collected and neutrophil to lymphocyte ratios (NLR) were calculated. Our primary outcome was 28-day mortality. Univariate and multivariate logistic regression models and cox proportional risk model were used to analyze the association between the leukocytes kinetics during first 3 days after ICU admission and the day-28 mortality.A total of 1245 septic shock patients with a 28-day mortality of 35.02% were included into analysis. There were no significant difference of lymphocyte number (0.83 ±â€Š0.02 vs 0.80 ±â€Š0.04, P = .552) between survival and non-survivals on day 1. However, the lymphocyte counts was significantly lower (0.95 ±â€Š0.03 vs 0.85 ±â€Š0.04, P = .024) on the third day. Both multivariate logistic and Cox regression analysis showed that lymphocyte counts on day 3 were associated with day-28 mortality. Moreover, Kaplan-Meier survival analysis revealed that increasing in lymphocyte counts and decreasing WBC, neutrophils and NLR during the first 3 days after diagnosis were associated with longer survival.Leukocytes kinetics during the first 3 days is a valuable prognostic marker in patients with septic shock in the ICU.