Within two decades, there have emerged three highly pathogenic and deadly human coronaviruses, namely SARS-CoV, MERS-CoV and SARS-CoV-2. The economic burden and health threats caused by these coronaviruses are extremely dreadful and getting more serious as the increasing number of global infections and attributed deaths of SARS-CoV-2 and MERS-CoV. Unfortunately, specific medical countermeasures for these hCoVs remain absent. Moreover, the fast spread of misinformation about the ongoing SARS-CoV-2 pandemic uniquely places the virus alongside an annoying infodemic and causes unnecessary worldwide panic. SARS-CoV-2 shares many similarities with SARS-CoV and MERS-CoV, certainly, obvious differences exist as well. Lessons learnt from SARS-CoV and MERS-CoV, timely updated information of SARS-CoV-2 and MERS-CoV, and summarized specific knowledge of these hCoVs are extremely invaluable for effectively and efficiently contain the outbreak of SARS-CoV-2 and MERS-CoV. By gaining a deeper understanding of hCoVs and the illnesses caused by them, we can bridge knowledge gaps, provide cultural weapons for fighting and controling the spread of MERS-CoV and SARS-CoV-2, and prepare effective and robust defense lines against hCoVs that may emerge or reemerge in the future. To this end, the stateof-the-art knowledge and comparing the biological features of these lethal hCoVs and the clinical characteristics of illnesses caused by them are systematically summarized in the review.

To investigate the feasibility of lung ultrasound in evaluating coronavirus disease 2019 and distinguish the sonographic features between COVID-19 and community-acquired pneumonia (CAP), a total of 12 COVID-19 patients and 20 CAP patients were selected and underwent lung ultrasound. The modified Buda scoring system for interstitial lung disease was used to evaluate the severity and treatment effect of COVID-19 on ultrasonography. The differences between modified lung ultrasound (MLUS) score and high-resolution computed tomography (HRCT) Warrick score were analyzed to evaluate their correlation. COVID-19 showed the following sonographic features: thickening (12/12), blurred (9/12), discontinuous (6/12) pleural line; rocket sign (4/12), partially diffused B-line (12/12), completely diffused B-line (10/12), waterfall sign (4/12); C-line sign (5/12); pleural effusion (1/12) and pulmonary balloon (Am line, 1/12). The last two features were rarely seen. Differences of ultrasonic features, including lesion range, lung signs and pneumonia-related complications, between COVID-19 and CAP were statistically significant (p ˂ 0.05 or 0.001). MLUS scores (p = 0.006) and HRCT Warrick scores (p = 0.015) increased as the severity of COVID-19 increased. The differences between moderate (29.00 [25.75À37.50]) and severe (43.00 [38.75À47.25]) (p = 0.022) or between moderate and critical (47.50 [44.25À50.00]) (p = 0.002) type COVID-19 were statistically significant, compared with those between severe and critical types. Correlation between MLUS scores and HRCT Warrick scores was positive (r = 0.54, p = 0.048). MLUS scores (Z = 2.61, p = 0.009) and HRCT Warrick scores (Z = 2.63, p = 0.009) of five severe or critical COVID-19 patients significantly decreased as their conditions improved after treatment. The differences of sonographic features between COVID-19 and CAP patients were notable. The MLUS scoring system could be used to evaluate the severity and treatment effect of COVID-19.

The aim of the work described here was to investigate the value of point-of-care ultrasound (POCUS) in the early assessment of the severity of pulmonary edema in rabbits. A rabbit oleic acid (OA)-induced pulmonary edema model was used. Thirty-two New Zealand rabbits were randomly divided into four groups: a control group and three pulmonary edema groups (mild, moderate and severe). Features of transthoracic B-line artifacts (BLA), blood pH, PaO 2 and PaCO 2 , serum inflammatory factors, lung coefficient (LC), lung wet-to-dry weight ratio (W/D) and lung histopathology were assessed. BLA features and severity of pulmonary edema were semiquantitatively scored. Correlations between the number of BLA and PaO 2 , PaCO 2 , serum inflammatory factors, LC and W/D were analyzed. An additional 8 rabbits with severe pulmonary edema were used as the verified group, in which the lung was divided into ex vivo BLA (BLA-ev)-free (BLA-ev-free) and BLA-ev-clustered subregions depending on the features of BLA-ev recorded by ex vivo lung ultrasound. Lung specimens from each subregion were collected for histopathological examination. Relationships between features of BLA-ev and lung histopathological abnormalities were analyzed. With increasing doses of OA, number of BLA, W/D and levels of serum inflammatory factors decreased. Meanwhile, lung pathologic abnormalities were aggravated. In addition, time of appearance of BLA, blood pH and PaO 2, and PaCO 2 decreased dose dependently on OA (p < 0.05). Number of BLA was linear positively correlated with severity of pulmonary edema (r = 0.953, p < 0.05). Consistently, the features of BLA-ev reflected the severity of lung histopathological abnormalities (r = 0.936, p < 0.05). Thus, POCUS is useful in the early quantitative assessment of the severity of pulmonary edema.

Sepsis, a potentially lethal condition resulting from failure to control the initial infection, is associated with a dysregulated host defense response to pathogens and their toxins. Sepsis remains a leading cause of morbidity, mortality and disability worldwide. The pathophysiology of sepsis is very complicated and is not yet fully understood. Worse still, the development of effective therapeutic agents is still an unmet need and a great challenge. Gases, including nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S), are small-molecule biological mediators that are endogenously produced, mainly by enzyme-catalyzed reactions. Accumulating evidence suggests that these gaseous mediators are widely involved in the pathophysiology of sepsis. Many sepsis-associated alterations, such as the elimination of invasive pathogens, the resolution of disorganized inflammation and the preservation of the function of multiple organs and systems, are shaped by them. Increasing attention has been paid to developing therapeutic approaches targeting these molecules for sepsis/septic shock, taking advantage of the multiple actions played by NO, CO and H2S. Several preliminary studies have identified promising therapeutic strategies for gaseous-mediator-based treatments for sepsis. In this review article, we summarize the state-of-the-art knowledge on the pathophysiology of sepsis; the metabolism and physiological function of NO, CO and H2S; the crosstalk among these gaseous mediators; and their crucial effects on the development and progression of sepsis. In addition, we also briefly discuss the prospect of developing therapeutic interventions targeting these gaseous mediators for sepsis.

Background Chronic obstructive pulmonary disease (COPD) is a frequently encountered disease condition in clinical practice mainly caused by cigarette smoke (CS). The aim of this study was to investigate the protective roles of human adipose-derived stem cells-derived exosomes (ADSCs-Exo) in CS-induced lung inflammation and injury and explore the underlying mechanism by discovering the effects of ADSCs-Exo on alveolar macrophages (AMs) pyroptosis. Methods ADSCs were isolated from human adipose tissues harvested from three healthy donors, and then ADSCs-Exo were isolated. In vivo, 24 age-matched male C57BL/6 mice were exposed to CS for 4 weeks, followed by intratracheal administration of ADSCs-Exo or phosphate buffered saline. In vitro, MH-S cells, derived from mouse AMs, were stimulated by 2% CS extract (CSE) for 24 h, followed by the treatment of ADSCs-Exo or phosphate buffered saline. Pulmonary inflammation was analyzed by detecting pro-inflammatory cells and mediators in the bronchoalveolar lavage fluid. Lung histology was assessed by hematoxylin and eosin staining. Mucus production was determined by Alcian blue-periodic acid-Schiff staining. The profile of AMs pyroptosis was evaluated by detecting the levels of pyroptosis-indicated proteins. The inflammatory response in AMs and the phagocytic activity of AMs were also investigated. Results In mice exposed to CS, the levels of pro-inflammatory cells and mediators were significantly increased, mucus production was markedly increased and lung architecture was obviously disrupted. AMs pyroptosis was elevated and AMs phagocytosis was inhibited. However, the administration of ADSCs-Exo greatly reversed these alterations caused by CS exposure. Consistently, in MH-S cells with CSE-induced properties modelling those found in COPD, the cellular inflammatory response was elevated, the pyroptotic activity was upregulated while the phagocytosis was decreased. Nonetheless, these abnormalities were remarkably alleviated by the treatment of ADSCs-Exo. Conclusions ADSCs-Exo effectively attenuate CS-induced airway mucus overproduction, lung inflammation and injury by inhibiting AMs pyroptosis. Therefore, hADSCs-Exo may be a promising cell-free therapeutic candidate for CS-induced lung inflammation and injury.