Activated Clec4nhi Neutrophils Aggravate Lung Injury in an Endothelial IGFBP7-Dependent Manner.

The role of endothelial cells in acute lung injury (ALI) has been widely elaborated, but little is known about the role of different subtypes of endothelial cells in ALI. ALI models were established by lipopolysaccharide. Single-cell RNA sequencing was used to identify differential molecules in endothelial subtypes and the heterogeneity of lung immune cells. Specific antibodies were used to block insulin-like growth factor binding protein 7 (IGFBP7), and AAVshIGP7 was used to specifically knock down IGFBP7. Here, we found that IGFBP7 was the most differentially expressed molecule in diverse subsets of endothelial cells and that IGFBP7 was strongly associated with inflammatory responses. Elevated IGFBP7 significantly exacerbated barrier dysfunction in ALI, whereas blockade of IGFBP7 partially reversed barrier damage. General capillary cells are the primary source of elevated serum IGFBP7 after ALI. Using single-cell RNA sequencing, we identified significantly increased Clec4nhi neutrophils in mice with ALI, whereas IGFBP7 knockdown significantly reduced infiltration of Clec4nhi cells and mitigated barrier dysfunction in ALI. In addition, we found that IGFBP7 activated the NF-κB signaling axis by promoting phosphorylation and ubiquitination degradation of F-box/WD repeat-containing protein 2 (FBXW2), thereby exacerbating barrier dysfunction in ALI. Taken together, our data indicate that blockade of serum IGFBP7 or IGFBP7 depletion in general capillary cells reversed barrier damage in ALI. Therefore, targeting IGFBP7 depletion could be a novel strategy for treating ALI.

Circulating microvesicles miR139-3p from bronchopulmonary dysplasia aggravates pulmonary vascular simplification by targeting 4E binding protein 1.

BACKGROUND: Microvesicles (MVs) play a crucial role in bronchopulmonary dysplasia (BPD). There are many MVs in circulating plasma, and they are in direct contact with lung endothelial cells. However, the molecular mechanism and causative effect of circulating MVs on BPD remain unclear. METHODS: Clinical plasma samples were collected, circulating MVs were isolated, and microRNA (miRNA) sequencing was performed. The BPD model was established, and different MVs were administered. Alveoli and pulmonary vessels were examined by hematoxylin-eosin staining, and body weight and length were measured. In vitro, gene expression was disrupted by miRNA mimics, miRNA inhibitors or plasmid transfection. Cell proliferation and protein expression were detected by cell scratch assay, accurate 5-ethynyl-2-deoxyuridine test, western blotting, or immunofluorescence assay. RESULTS: BPD-derived MVs further aggravated pulmonary vascular simplification, while circulating MVs from control mice mitigated pulmonary vascular simplification. Micro-RNA sequencing and independent sample verification revealed that miR139-3p, but not miR6125 or miR193b-3p, was the most critical effector molecule in MVs. Mechanism studies showed that eukaryotic translation initiation factor 4E binding protein 1 was the target gene for miR139-3p. In addition, we found that supplementation of miR139-3p inhibitor partially alleviated pulmonary vascular simplification. CONCLUSIONS: These results indicate that circulating MVs are involved in forming BPD by carrying miR139-3p molecules and support miR139-3p inhibitors as a potential therapeutic strategy for alleviating pulmonary vascular simplification in BPD.

S1PR3 inhibition protects against LPS-induced ARDS by inhibiting NF-κB and improving mitochondrial oxidative phosphorylation.

BACKGROUND: Inflammation and endothelial barrier dysfunction are the major pathophysiological changes in acute respiratory distress syndrome (ARDS). Sphingosine-1-phosphate receptor 3 (S1PR3), a G protein-coupled receptor, has been found to mediate inflammation and endothelial cell (EC) integrity. However, the function of S1PR3 in ARDS has not been fully elucidated. METHODS: We used a murine lipopolysaccharide (LPS)-induced ARDS model and an LPS- stimulated ECs model to investigate the role of S1PR3 in anti-inflammatory effects and endothelial barrier protection during ARDS. RESULTS: We found that S1PR3 expression was increased in the lung tissues of mice with LPS-induced ARDS. TY-52156, a selective S1PR3 inhibitor, effectively attenuated LPS-induced inflammation by suppressing the expression of proinflammatory cytokines and restored the endothelial barrier by repairing adherens junctions and reducing vascular leakage. S1PR3 inhibition was achieved by an adeno-associated virus in vivo and a small interfering RNA in vitro. Both the in vivo and in vitro studies demonstrated that pharmacological or genetic inhibition of S1PR3 protected against ARDS by inhibiting the NF-κB pathway and improving mitochondrial oxidative phosphorylation. CONCLUSIONS: S1PR3 inhibition protects against LPS-induced ARDS via suppression of pulmonary inflammation and promotion of the endothelial barrier by inhibiting NF-κB and improving mitochondrial oxidative phosphorylation, indicating that S1PR3 is a potential therapeutic target for ARDS.

Omentin-1 ameliorates pulmonary arterial hypertension by inhibiting endoplasmic reticulum stress through AMPKα signaling.

BACKGROUND: Endothelial dysfunction of the pulmonary artery contributes to hypoxia-induced pulmonary arterial hypertension (PAH). Omentin-1, as a novel adipocytokine, plays an important protective role against cardiovascular diseases. However, the effect and underlying mechanisms of omentin-1 against PAH remain unclear. METHODS: PAH was induced in SD (Sprague & Dawley) rats via a low-oxygen chamber for 4 weeks. Hemodynamic evaluation was undertaken using a PowerLab data acquisition system, and histopathological analysis was stained with hematoxylin and eosin (H&E). Endothelial function of pulmonary artery was assessed using wire myography. RESULTS: We found that omentin-1 significantly improved pulmonary endothelial function in rats exposed to hypoxia and attenuated PAH. Mechanistically, we found that omentin-1 increased phosphorylated 5'­adenosine monophosphate­activated protein kinase (p­AMPK) level and reduced endoplasmic reticulum (ER) stress and increased NO production in pulmonary artery from rats exposed to hypoxia. However, the effect of omentin-1 was abolished by treatment with AMPK inhibitor (Compound C). CONCLUSIONS: Our results reveal a protective effect of omentin-1 in PAH via inhibiting ER stress through AMPKα signaling and provide an agent with translational potential for the treatment of PAH.

Interferon regulatory factor 1 (IRF1) inhibits lung endothelial regeneration following inflammation-induced acute lung injury.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a respiratory condition caused by severe endothelial barrier dysfunction within the lung. In ARDS, excessive inflammation, tissue edema, and immune cell influx prevents endothelial cell regeneration that is crucial in repairing the endothelial barrier. However, little is known about the molecular mechanism that underpin endothelial cell regeneration in ARDS. METHODS: R-based bioinformatics tools were used to analyze microarray-derived transcription profiles in human lung microvascular endothelial cells (HLMVECs) subjected to non-treatment or lipopolysaccharide (LPS) exposure. We generated endothelial cell-specific interferon regulatory factor 1 (Irf1) knockout (Irf1EC-/-) and Irf1fl/fl control mice for use in an endotoxemic murine model of acute lung injury (ALI). In vitro studies (qPCR, immunoblotting, and ChIP-qPCR) were conducted in mouse lung endothelial cells (MLECs) and HLMVECs. Dual-luciferase promoter reporter assays were performed in HLMVECs. RESULTS: Bioinformatics analyses identified IRF1 as a key up-regulated gene in HLMVECs post-LPS exposure. Endothelial-specific knockout of Irf1 in ALI mice resulted in enhanced regeneration of lung endothelium, while liposomal delivery of endothelial-specific Irf1 to wild-type ALI mice inhibited lung endothelial regeneration in a leukemia inhibitory factor (Lif)-dependent manner. Mechanistically, we demonstrated that LPS-induced Stat1Ser727 phosphorylation promotes Irf1 transactivation, resulting in downstream up-regulation of Lif that inhibits endothelial cell proliferation. CONCLUSIONS: These results demonstrate the existence of a p-Stat1Ser727-Irf1-Lif axis that inhibits lung endothelial cell regeneration post-LPS injury. Thus, direct inhibition of IRF1 or LIF may be a promising strategy for enhancing endothelial cell regeneration and improving clinical outcomes in ARDS patients.

Comprehensive Comparisons between Directing and Alternating Current Electrolysis in Organic Synthesis.

Organic electrosynthesis has consistently aroused significant interest within both academic and industrial spheres. Despite the considerable progress achieved in this field, the majority of electrochemical transformations have been conducted through the utilization of direct-current (DC) electricity. In contrast, the application of alternating current (AC), characterized by its polarity-alternating nature, remains in its infancy within the sphere of organic synthesis, primarily due to the absence of a comprehensive theoretical framework. This minireview offers an overview of recent advancements in AC-driven organic transformations and seeks to elucidate the differences between DC and AC electrolytic methodologies by probing into their underlying physical principles. These differences encompass the ability of AC to preclude the deposition of metal catalysts, the precision in modulating oxidation and reduction intensities, and the mitigation of mass transfer processes.

An online nomogram of acute respiratory distress syndrome originating from pulmonary disease.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a highly heterogeneous disease accompanied by high mortality. Our goal was to investigate the risk factors for 28-day mortality and then establish a predictive online nomogram for ARDS originating from pulmonary disease (ARDSp). METHODS: We examined 1087 patients diagnosed with ARDS from January 2010 to December 2019 at the Second Affiliated Hospital of Chongqing Medical University. A total of 185 ARDSp patients were finally enrolled in the training cohort. A total of 43 ARDSp patients from January 2020 to August 2021 in the Second Affiliated Hospital of Chongqing Medical University and the Traditional Chinese Medical Hospital of Jiangbei District were included in the external validation cohort. Fundamental, clinical and laboratory variables at admission were gathered from medical records, and the 28-day prognosis was followed up. RESULTS: In the training cohort, it was found that age, sex, C-reactive protein, albumin and multiple organ dysfunction syndrome (MODS) were independent risk factors for 28-day mortality via multivariate logistic regression. The online nomogram software for 28-day mortality showed good discrimination, calibration and clinical utility in both the training cohort and external validation cohort. CONCLUSIONS: For ARDSp patients, older males, lower C-reactive protein and albumin levels, and MODS were independent predictors of a poor 28-day prognosis. The online nomogram based on five independent factors could act as a predictive appliance in clinical practice.

The Establishment of China Bronchiectasis Registry and Research Collaboration (BE-China): Protocol of a prospective multicenter observational study.

BACKGROUND: Bronchiectasis is a highly heterogeneous chronic airway disease with marked geographic and ethnic variations. Most influential cohort studies to date have been performed in Europe and USA, which serve as the examples for developing a cohort study in China where there is a high burden of bronchiectasis. The Establishment of China Bronchiectasis Registry and Research Collaboration (BE-China) is designed to: (1) describe the clinical characteristics and natural history of bronchiectasis in China and identify the differences of bronchiectasis between the western countries and China; (2) identify the risk factors associated with disease progression in Chinese population; (3) elucidate the phenotype and endotype of bronchiectasis by integrating the genome, microbiome, proteome, and transcriptome with detailed clinical data; (4) facilitate large randomized controlled trials in China. METHODS: The BE-China is an ongoing prospective, longitudinal, multi-center, observational cohort study aiming to recruit a minimum of 10,000 patients, which was initiated in January 2020 in China. Comprehensive data, including medical history, aetiological testing, lung function, microbiological profiles, radiological scores, comorbidities, mental status, and quality of life (QoL), will be collected at baseline. Patients will be followed up annually for up to 10 years to record longitudinal data on outcomes, treatment patterns and QoL. Biospecimens, if possible, will be collected and stored at - 80 °C for further research. Up to October 2021, the BE-China has enrolled 3758 patients, and collected 666 blood samples and 196 sputum samples from 91 medical centers. The study protocol has been approved by the Shanghai Pulmonary Hospital ethics committee, and all collaborating centers have received approvals from their local ethics committee. All patients will be required to provide written informed consent to their participation. CONCLUSIONS: Findings of the BE-China will be crucial to reveal the clinical characteristics and natural history of bronchiectasis and facilitate evidence-based clinical practice in China. Trial registration Registration Number in ClinicalTrials.gov: NCT03643653.

Protective effects of adipose-derived biogenic nanoparticles on the pulmonary microvascular endothelial barrier in mice with ventilator-induced lung injury via the TRPV4/ROCK1 signalling pathway.

PURPOSE: The "obesity paradox" phenomenon occurs in critically ill patients who receive mechanical ventilation. Our previous studies found that the adipose-derived exosomes secreted by obese mice have a protective effect on the pulmonary microvascular endothelial barrier. However, the extraction of exosomes is cumbersome, their yield is low, and their storage is difficult. After further research, we discovered a new type of adipose-derived bioactive material called: lipoaspirate nanoparticles (Lipo-NPs). METHODS: Lipo-NPs were extracted and identified using a tangential flow filtration system. The Lipo-NPs were used as an intervention in ventilator-induced lung injury (VILI) models in vivo and in vitro to investigate whether they have a protective effect on lung tissue damage (haematoxylin and eosin staining), lung barrier function (lung wet/dry [W/D] weight ratio, protein concentration in bronchoalveolar lavage fluid (BALF), and Vascular endothelial (VE)-expression), as well as their related mechanisms. RESULTS: In both in vivo and in vitro studies, Lipo-NPs can attenuate lung injury, reduce lung W/D ratio and protein concentration in BALF, and augment the expression of the adhesion link-protein VE-cadherin, thus playing a protective role in lung barrier function. This protective effect involves the activation of the transient receptor potential vanilloid 4 (TRPV4)/Rho-associated kinase1 (ROCK1) signalling pathway. We further verified the role of this signalling pathway via activation and inhibition of TRPV4 and ROCK1. Moreover, phosphorylation of myosin light chain 2 (MLC2) regulates F-actin and is a target of the ROCK pathway. CONCLUSION: Lipo-NPs can enhance the expression of VE-cadherin by inhibiting the TRPV4/ROCK1/pMLC2 signalling pathway in the mechanical ventilation model, thereby exerting a protective effect on the VILI pulmonary microvascular endothelial barrier.

Comparison of Clinical Characteristics and Predictors of Mortality between Direct and Indirect ARDS.

Background and Objectives: Acute Respiratory Distress Syndrome (ARDS) is a heterogeneous syndrome that encompasses lung injury from a direct pulmonary or indirect systemic insult. Studies have shown that direct and indirect ARDS differ in their pathophysiologic process. In this study, we aimed to compare the different clinical characteristics and predictors of 28-day mortality between direct and indirect ARDS. Materials and Methods: The data of 1291 ARDS patients from September 2012 to December 2021 at the Second Affiliated Hospital of Chongqing Medical University were reviewed. We enrolled 451 ARDS patients in our study through inclusion and exclusion criteria. According to the risk factors, each patient was divided into direct (n = 239) or indirect (n = 212) ARDS groups. The primary outcome was 28-day mortality. Results: The patients with direct ARDS were more likely to be older (p < 0.001) and male (p = 0.009) and have more comorbidity (p < 0.05) and higher 28-day mortality (p < 0.001) than those with indirect ARDS. Age and multiple organ dysfunction syndrome (MODS) were predictors of 28-day mortality in the direct ARDS group, while age, MODS, creatinine, prothrombin time (PT), and oxygenation index (OI) were independent predictors of 28-day mortality in the indirect ARDS group. Creatinine, PT, and OI have interactions with ARDS types (all p < 0.01). Conclusions: The patients with direct ARDS were more likely to be older and male and have worse conditions and prognoses than those with indirect ARDS. Creatinine, PT, and OI were predictors of 28-day mortality only in the indirect ARDS group. The differences between direct and indirect ARDS suggest the need for different management strategies of ARDS.

Alternating Current Electrolysis Enabled Formal C-O/O-H Cross-Metathesis of 4-Alkoxy Anilines with Alcohols.

While multiple bond metathesis reactions, for example olefin metathesis, have seen considerable recent progress, direct metathesis of traditionally inert C-O single bonds is extremely rare and particularly challenging. Undoubtedly, metathesis reaction of C-O bonds is one of the most ideal routes for the value-added upgrading of molecules involving C-O bonds. Reported here is a new protocol to achieve the formal C-O/O-H cross-metathesis via alternating current electrolysis. Featuring mild reaction conditions, the protocol allows readily available 4-alkoxy anilines and alcohols to be converted into a wide range of valuable products in highly regioselective and chemoselective manner. Moreover, the present strategy can be used in the late-stage modification of pharmaceuticals as well as biologically active compounds, which demonstrated the potential application.

A trauma-related survival predictive model of acute respiratory distress syndrome.

PURPOSE: The purpose of this study was to construct and validate a simple model for the prediction of survival in patients with trauma-related ARDS. METHODS: This is a single-center, retrospective cohort study using MIMIC-III Clinical Database. RESULTS: 842 patients were included in this study. 175 (20.8%) died in-hospital, whereas 215 (25.5%) died within 90 days. The deceased group had higher Acute Physiology Score (APS III), Sequential Organ Failure Assessment (SOFA), and Simplified Acute Physiology Score II (SAPS II). In multivariate logistic regression model, independent risk factors for mortality in ARDS patients included age ([odds ratio] OR, 1.035; 95% confidence interval [CI], 1.020-1.049), body mass index (OR, 0.957; 95% CI, 0.926-0.989), red blood cell distribution width (OR, 1.283; 95% CI, 1.141-1.443), hematocrit (OR, 1.055; 95% CI, 1.017-1.095), lactate (OR, 1.226; 95% CI, 1.127-1.334), blood urea nitrogen (OR, 1.025; 95% CI, 1.007-1.044), acute kidney failure (OR, 1.875; 95% CI, 1.188-2.959), sepsis (OR, 1.917; 95% CI, 1.165-3.153), type of admission (emergency vs. elective [OR, 2.822; 95% CI, 1.647-4.837], and urgent vs. elective [OR, 5.156; 95% CI, 1.896-14.027]). The area under the curve (AUC) of the model was 0.826, which was superior than the SAPS II (0.776), APS III (0.718), and SOFA (0.692). In the cross-validation model, the accuracy of the test set was 0.823, the precision was 0.643, and the AUC was 0.813. CONCLUSIONS: We established a prediction model using data commonly used in the clinic, which has high accuracy and precision and is worthy of use in clinical practice.

Serum MCP-1 and NGAL Play an Important Role in the Acute Inflammatory Event of Chronic Obstructive Pulmonary Disease.

NGAL is mainly secreted by neutrophils which play the core role in AECOPD. MCP-1 is secreted specifically by monocytes and macrophages. Both biomarkers are involved in the core process of acute inflammatory reaction in COPD. So We analyzed serum NGAL and MCP-1levels to explore their potential clinical values in the chronic obstructive pulmonary disease (COPD) .This study enrolled 97 COPD patients and 50 healthy controls. All participants received blood collection and lung function test and arterial blood gas measurements. The expression levels of serum NGAL and MCP-1 were measured by ELISA. The serum NGAL and MCP-1 levels of COPD with community-acquired pneumonia (COPD-CAP) patients were significantly higher than those of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients and healthy adults. The NGAL levels of the GOLD III and IV groups were significantly higher than those of the GOLD II group. Spearman correlation analysis showed a negative correlation between NGAL and FEV1%pred, FVC% pred. ROC curves indicated that NGAL has a high diagnostic value for both AECOPD and COPD-CAP. NGAL has the value of distinguishing GOLD I and II from GOLD III and IV. MCP-1 have moderate diagnostic value for COPD-CAP and can differentiate COPD-CAP from AECOPD. This study shows NGAL has certain diagnostic value for AECOPD and COPD-CAP, but can not distinguish the two. NGAL is closely related to airway remodeling and can be used as a potential indicator to distinguish the higher GOLD degree. MCP-1 can be used as potential indicator for the diagnosis of COPD-CAP.

A Peptide-Based Magnetic Chemiluminescence Enzyme Immunoassay for Serological Diagnosis of Coronavirus Disease 2019.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel ß-coronavirus, causes severe pneumonia and has spread throughout the globe rapidly. The disease associated with SARS-CoV-2 infection is named coronavirus disease 2019 (COVID-19). To date, real-time reverse-transcription polymerase chain reaction (RT-PCR) is the only test able to confirm this infection. However, the accuracy of RT-PCR depends on several factors; variations in these factors might significantly lower the sensitivity of detection. METHODS: In this study, we developed a peptide-based luminescent immunoassay that detected immunoglobulin (Ig)G and IgM. The assay cutoff value was determined by evaluating the sera from healthy and infected patients for pathogens other than SARS-CoV-2. RESULTS: To evaluate assay performance, we detected IgG and IgM in the sera from confirmed patients. The positive rate of IgG and IgM was 71.4% and 57.2%, respectively. CONCLUSIONS: Therefore, combining our immunoassay with real-time RT-PCR might enhance the diagnostic accuracy of COVID-19.

Adipose-derived exosomes protect the pulmonary endothelial barrier in ventilator-induced lung injury by inhibiting the TRPV4/Ca2+ signaling pathway.

Mechanical ventilation (MV) is the main supportive treatment of acute respiratory distress syndrome (ARDS), but it may lead to ventilator-induced lung injury (VILI). Large epidemiological studies have found that obesity was associated with lower mortality in mechanically ventilated patients with acute lung injury, which is known as "obesity paradox." However, the effects of obesity on VILI are unknown. In the present study, wild-type mice were fed a high-fat diet (HFD) and ventilated with high tidal volume to investigate the effects of obesity on VILI in vivo, and pulmonary microvascular endothelial cells (PMVECs) were subjected to 18% cyclic stretching (CS) to further investigate its underlying mechanism in vitro. We found that HFD protects mice from VILI by alleviating the pulmonary endothelial barrier injury and inflammatory responses in mice. Adipose-derived exosomes can regulate distant tissues as novel adipokines, providing a new mechanism for cell-cell interactions. We extracted three adipose-derived exosomes, including HFD mouse serum exosome (S-Exo), adipose tissue exosome (AT-Exo), and adipose-derived stem cell exosome (ADSC-Exo), and further explored their effects on MV or 18% CS-induced VILI in vivo and in vitro. Administration of three exosomes protected against VILI by suppressing pulmonary endothelial barrier hyperpermeability, repairing the expression of adherens junctions, and alleviating inflammatory response in vivo and in vitro, accompanied by transient receptor potential vanilloid 4 (TRPV4)/Ca2+ pathway inhibition. Collectively, these data indicated that HFD-induced obesity plays a protective role in VILI by alleviating the pulmonary endothelial barrier injury and inflammatory response via adipose-derived exosomes, at least partially, through inhibiting the TRPV4/Ca2+ pathway.

Tangeretin attenuates lipopolysaccharide-induced acute lung injury through Notch signaling pathway via suppressing Th17 cell response in mice.

Tangeretin, a polymethoxylated flavonoid is abundant in citrus fruits, which has been reported to inhibit inflammation by inhibiting NF-κB activation and proinflammatory cytokines. Notch blockage inhibits Th17 cells response that are involved in the development of acute lung injury (ALI). This study investigated the protective effects of tangeretin on LPS-induced ALI in mice. Male C57BL/6 mice were treated with phosphate-buffered saline (PBS), lipopolysaccharide (LPS), LPS and tangeretin, or LPS and N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT, a Notch signaling inhibitor), which were harvested at 48 h after challenged by LPS. CD4+ T cells were treated with tangeretin or DAPT and harvested after 72 h. Tangeretin notably attenuated pathological changes and decreased the wet to dry weight ratio of the mouse lungs. The total cell and neutrophil counts, tumor necrosis factor (TNF)-α in bronchoalveolar lavage fluid (BALF), myeloperoxidase activity of lung tissue were markedly reduced by tangeretin. The percentage of CD4+IL-17 + T cells in the lungs and the concentration of interleukin (IL)-17 and IL-22 in BALF were significantly down-regulated by tangeretin. As with the positive control (DAPT), tangeretin inhibited the activity of the Notch signaling pathway accompanied with the down-regulation of acid-related orphan receptor gamma t and IL-23 receptor expression. This study demonstrated that tangeretin protects against LPS-induced ALI by suppressing Th17 response at least partially, through a Notch-dependent mechanism.

Positive results for patients with COVID-19 discharged form hospital in Chongqing, China.

BACKGROUND: Since December 2019, over 80,000 patients with coronavirus disease 2019 (COVID-19) have been confirmed in China. With the increasing number of recovered patients, more attention should be paid to the follow-up of these patients. METHODS: In the study, 576 patients with COVID-19 discharged from hospital in Chongqing, China from January 24, 2020, to March 10, 2020 were evaluated by viral nucleic acid tests for severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) to determine if they could be released from quarantine. Among the 576 patients, 61 patients (10.6%) had positive RT-PCR test results of SARS-CoV-2. We aimed to analyze the demographics, clinical characteristics and treatment of 61 patients. RESULTS: These positive patients were characterized by older age, chronic medical illness and mild conditions. 38 (62.3%) patients who were asymptomatic without abnormalities on chest radiographs were found in the positive with COVID-19. Also, they showed positive results of stool or sputum specimens with negative results of nasal and pharyngeal swab specimens. The median duration of positive result of SARS-CoV-2 was varied from 3 days to 35 days in the patients discharged from hospital with no family member infection. CONCLUSIONS: Multi-site screening of SARS-CoV-2 including nasal and pharyngeal swabs, stool and sputum specimens could be considered to improve the diagnosis, treatment and infection control in patients with COVID-19. Our findings provide the important information and clinical evidence for the improved management of patients recovered from COVID-19.

Incidence and outcomes of acute respiratory distress syndrome in intensive care units of mainland China: a multicentre prospective longitudinal study.

OBJECTIVES: To evaluate the incidence and mortality of acute respiratory distress syndrome (ARDS) in medical/respiratory intensive care units (MICUs/RICUs) to assess ventilation management and the use of adjunct therapy in routine clinical practice for patients fulfilling the Berlin definition of ARDS in mainland China. METHODS: This was a multicentre prospective longitudinal study. Patients who met the Berlin definition of ARDS were included. Baseline data and data on ventilator management and the use of adjunct therapy were collected. RESULTS: Of the 18,793 patients admitted to participating ICUs during the study timeframe, 672 patients fulfilled the Berlin ARDS criteria and 527 patients were included in the analysis. The most common predisposing factor for ARDS in 402 (77.0) patients was pneumonia. The prevalence rates were 9.7% (51/527) for mild ARDS, 47.4% (250/527) for moderate ARDS, and 42.9% (226/527) for severe ARDS. In total, 400 (75.9%) patients were managed with invasive mechanical ventilation during their ICU stays. All ARDS patients received a tidal volume of 6.8 (5.8-7.9) mL/kg of their predicted body weight and a positive end-expository pressure (PEEP) of 8 (6-12) cmH2O. Recruitment manoeuvres (RMs) and prone positioning were used in 61 (15.3%) and 85 (16.1%) ventilated patients, respectively. Life-sustaining care was withdrawn from 92 (17.5%) patients. When these patients were included in the mortality analysis, 244 (46.3%) ARDS patients (16 (31.4%) with mild ARDS, 101 (40.4%) with moderate ARDS, and 127 (56.2%) with severe ARDS) died in the hospital. CONCLUSIONS: Among the 18 ICUs in mainland China, the incidence of ARDS was low. The rates of mortality and withdrawal of life-sustaining care were high. The recommended lung protective strategy was followed with a high degree of compliance, but the implementation of adjunct treatment was lacking. These findings indicate the potential for improvement in the management of patients with ARDS in China. TRIAL REGISTRATION: Clinicaltrials.gov NCT02975908 . Registered on 29 November 2016-retrospectively registered.

Diagnostic value of peripheral hematologic markers for coronavirus disease 2019 (COVID-19): A multicenter, cross-sectional study.

BACKGROUND: To determine the diagnostic value of hematologic markers for coronavirus disease 2019 (COVID-19) and explore their relationship with disease severity. METHODS: Subjects included 190 COVID-19 patients, 190 healthy subjects, and 105 influenza pneumonia (IP) patients. COVID-19 patients were divided into the ARDS and non-ARDS groups. Routine blood examination, biochemistry indicator, days in hospital, body temperature, pneumonia severity index (PSI), CURB-65, and MuLBSTA were recorded. Correlations between variables were assessed using Spearman's correlation analysis. Receiver operating characteristic (ROC) curves were used to study the accuracy of the various diagnostic tests. RESULTS: Compared with healthy subjects, COVID-19 patients had lower white blood cell (WBC), lymphocyte, platelet, and hemoglobin levels; higher percentages of neutrophils and monocytes; lower percentages of lymphocytes and higher neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) values (P < .05). COVID-19 patients had higher WBC and neutrophil levels and lower percentages of lymphocytes compared to IP (P < .05). ROC curve analysis revealed that MLR had a high diagnostic value in differentiating COVID-19 patients from healthy subjects, but not from IP patients. NLR showed significant positive correlations with PSI, CURB-65, and MuLBSTA. Lymphocyte count was lower in the ARDS group and yielded a higher diagnostic value than the other variables. CONCLUSIONS: Monocyte-to-lymphocyte ratio showed an acceptable efficiency to separate COVID-19 patients from healthy subjects, but failed to rule out IP patients. NLR may be a reliable marker to evaluate the disease severity of COVID-19. Lymphocyte count may be useful to establish the early diagnosis of ARDS in the COVID-19 patients.