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BACKGROUND Acute lung injury (ALI) is a common and life-threatening complication of severe acute pancreatitis (SAP). There are currently limited effective treatment options for SAP and associated ALI. Calycosin (Cal), a bioactive constituent extracted from the medicinal herb Radix Astragali exhibits potent anti-inflammatory properties, but its effect on SAP and associated ALI has yet to be determined. AIM To identify the roles of Cal in SAP-ALI and the underlying mechanism. METHODS SAP was induced via two intraperitoneal injections of L-arg (4 g/kg) and Cal (25 or 50 mg/kg) were injected 1 h prior to the first L-arg challenge. Mice were sacrificed 72 h after the induction of SAP and associated ALI was examined histologically and biochemically. An in vitro model of lipopolysaccharide (LPS)-induced ALI was established using A549 cells. Immunofluorescence analysis and western blot were evaluated in cells. Molecular docking analyses were conducted to examine the interaction of Cal with HMGB1. RESULTS Cal treatment substantially reduced the serum amylase levels and alleviated histopathological injury associated with SAP and ALI. Neutrophil infiltration and lung tissue levels of neutrophil mediator myeloperoxidase were reduced in line with protective effects of Cal against ALI in SAP. Cal treatment also attenuated the serum levels and mRNA expression of pro-inflammatory cytokines tumor necrosis factor-α, interleukin-6, IL-1β, HMGB1 and chemokine (CXC motif) ligand 1 in lung tissue. Immunofluorescence and western blot analyses showed that Cal treatment markedly suppressed the expression of HMGB1 and phosphorylated nuclear factor-kappa B (NF-κB) p65 in lung tissues and an in vitro model of LPS-induced ALI in A549 cells suggesting a role for HGMB1 in the pathogenesis of ALI. Furthermore, molecular docking analysis provided evidence for the direct interaction of Cal with HGMB1. CONCLUSION Cal protects mice against L-arg-induced SAP and associated ALI by attenuating local and systemic neutrophil infiltration and inflammatory response via inhibition of HGMB1 and the NF-κB signaling pathway.

Background Acute pancreatitis (AP) is an inflammatory disease in which the regulatory pathway is complex and not well understood. Soluble suppression of tumorigenicity 2 (sST2) protein receptor functions as a decoy receptor for interleukin (IL)-33 to prevent IL-33/suppression of tumorigenicity 2L (ST2L)-pathway-mediated T helper (Th)2 immune responses. Aim To investigate the role of sST2 in AP. Methods We assessed the association between sST2 and severity of AP in 123 patients enrolled in this study. The serum levels of sST2, C-reactive protein (CRP) and Th1- and Th2-related cytokines, including interferon (IFN)-γ, tumor necrosis factor (TNF)-α, IL-2, IL-4, IL-5 and IL-13, were measured by highly sensitive ELISA, and the severity of AP in patients was evaluated by the 2012 Atlanta Classification Criteria. Results Serum sST2 levels were significantly increased in AP patients, and further, these levels were significantly elevated in severe AP (SAP) patients compared to moderately severe AP (MSAP) and mild AP (MAP) patients. Logistic regression showed sST2 was a predictor of SAP [odds ratio (OR): 1.003 (1.001-1.006), P = 0.000]. sST2 cutoff point was 1190 pg/mL, and sST2 above this cutoff was associated with SAP. sST2 was also a predictor of any organ failure and mortality during AP [OR: 1.006 (1.003-1.009), P = 0.000, OR: 1.002 (1.001-1.004), P = 0.012, respectively]. Additionally, the Th1-related cytokines IFN-γ and TNF-α in the SAP group were higher and the Th2-related cytokine IL-4 in the SAP group was significantly lower than those in MSAP and MAP groups. Conclusion sST2 may be used as a novel inflammatory marker in predicting AP severity and may regulate the function and differentiation of IL-33/ST2-mediated Th1 and Th2 Lymphocytes in AP homeostasis.

BACKGROUND: Weaning through noninvasive ventilation (NIV) after early extubation may facilitate invasive ventilation withdrawal and reduce related complications in patients with hypercapnic respiratory failure. However, the effects of NIV weaning are uncertain in patients with acute hypoxemic respiratory failure (AHRF). We aimed to investigate whether NIV weaning could reduce hospital mortality and other outcomes compared with invasive weaning in subjects with hypoxemic AHRF. METHODS: We searched medical literature databases for relevant articles published from inception to February 2019. Randomized controlled trials that adopted NIV as a weaning strategy compared with invasive weaning in hypoxemic AHRF were included. The primary outcome was hospital mortality. The secondary outcomes included ICU mortality, the ICU stay, weaning time, duration of ventilation, extubation failure, and adverse events. RESULTS: Six relevant studies, which involved 718 subjects, were included. There was no significant effect of NIV weaning on hospital mortality compared with invasive weaning (risk ratio 0.94, 95% CI 0.65–1.36; P = .74), whereas there was a significant effect of NIV weaning on shortening the ICU stay (mean difference −3.95, 95% CI −6.49 to −1.40, P = .002) and on decreasing adverse events without affecting the weaning time (standardized MD −0.04, 95% CI −0.21 to 0.14; P = .68). CONCLUSIONS: The strategy of NIV weaning did not decrease hospital mortality in subjects with hypoxemic AHRF, but it did shorten the ICU lengths of stay and reduce adverse events.

Chinese emergency department (ED) staff encountered significant mental stress while fighting the coronavirus disease 2019 (COVID-19) pandemic. We sought to investigate the prevalence and associated factors for depressive symptoms among ED staff (including physicians, nurses, allied health, and auxiliary ED staff). A cross-sectional national survey of ED staff who were on duty and participated in combating the COVID-19 pandemic was conducted March 1–15, 2020. A total of 6,588 emergency medical personnel from 1,060 hospitals responded to this survey. A majority of respondents scored above 10 points on the PHQ-9 standardized test, which is associated with depressive symptoms. Those aged 31–45, those working in the COVID-19 isolation unit, and those with relatives ≤ 16 or ≥70 years old at home all had statistically significant associations with scoring >10 points. Depressive symptoms among Chinese emergency medical staff were likely quite common during the response to the COVID-19 pandemic and reinforce the importance of targeted ED staff support during future outbreaks.

The present study investigates whether paraquat (PQ) regulates polarization of alveolar macrophages through glycolysis and promotes the occurrence of acute lung injury in rats. In vivo, the PQ intraperitoneal injection was used to construct a model of acute lung injury in rats. In vitro, the study measured the effect of different concentrations of PQ on the viability of the alveolar macrophages, and explored the polarization and glycolysis metabolism of alveolar macrophages at different time points after PQ intervention. Compared with the normal control (NC) group, the lung pathological damage in rats increased gradually after PQ poisoning, reaching a significant degree at 48 h after poisoning. The PQ-poisoned rat serum showed increased expressions of interleukin-6 (IL-6), tumor necrosis factor- α (TNF-α), and M1 macrophage marker, iNOS, while the expression of interleukin-10 (IL-10) and M2 macrophage marker, Arg1, decreased. The toxic effect of PQ on alveolar macrophages was dose- and time-dependent. Compared with the NC group, IL-6 and TNF-α in the cell supernatant gradually increased after PQ intervention, while the IL-10 content gradually decreased. The PQ intervention in alveolar macrophages increased the expression of intracellular glycolysis rate-limiting enzyme pyruvate kinase isozymes M1/M2 (PKM1/M2), lactate, lactate/pyruvate ratio, and the polarization of alveolar macrophage towards M1. Inhibition of cellular glycolysis significantly reduced the PQ-induced alveolar macrophage polarization to M1 type. Thus, PQ induced increased polarization of lung macrophages toward M1 and decreased polarization toward M2, promoting acute lung injury. Therefore, it can be concluded that PQ regulates the polarization of alveolar macrophages through glycolysis.

INTRODUCTION: Patients with cancer are more vulnerable to COVID-19 than the general population. Accordingly, it is necessary to identify the risk factors for death in patients with cancer and COVID-19. METHODS: PubMed, Cochrane Library, and Embase Ovid databases were searched for relevant articles published before July 31st, 2020. Studies that explored the risk factors for mortality were included. The effect size was relative risk (RR) and 95% confidence interval (CI). RESULTS: We included 17 observational studies involving 3268 patients. The pooled mortality was 24.8%. Male gender, age above 65 years, and comorbidities (especially hypertension and COPD) were risk factors for death (RR 1.16, 1.27, 1.12; 95% CI 0.7-1.95, 1.08-1.49, 1.04-1.2; P = 0.006, 0.004, and 0.002, respectively). Recent anti-cancer treatments did not increase mortality (P > 0.05). Dyspnea, cough, and sputum canused an elevated risk of death (P

Background Liver injury is one of the most common complications during sepsis. Macrophage migration inhibitory factor (MIF) is an important proinflammatory cytokine. This study explored the role of MIF in the lipopolysaccharide (LPS)-induced liver injury through genetically manipulated mouse strains. Methods The model of LPS-induced liver injury was established in wild-type and Mif-knockout C57/BL6 mice. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBil) were detected, and the expressions of MIF, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured. Liver histopathology was conducted to assess liver injury. Moreover, the inhibitions of MIF with (S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1) and 4-iodo-6-phenylpyrimidine (4-IPP) were used to evaluate their therapeutic potential of liver injury. Results Compared with wild-type mice, the liver function indices and inflammation factors presented no significant difference in the Mif−/− mice. After 72 h of the LPS-induced liver injury, serum levels of ALT, AST, and TBil as well as TNF-α and IL-1β were significantly increased, but the knockout of Mif attenuated liver injury and inflammatory response. In liver tissue, mRNA levels of TNF-α, IL-1β and NF-κB p65 were remarkably elevated in LPS-induced liver injury, while the knockout of Mif reduced these levels. Moreover, in LPS-induced liver injury, the inhibitions of MIF with ISO-1 and 4-IPP alleviated liver injury and slightly attenuated inflammatory response. Importantly, compared to mice with LPS-induced liver injury, Mif knockout or MIF inhibitions significantly prolonged the survival of the mice. Conclusions In LPS-induced liver injury, the knockout of Mif or MIF inhibitions alleviated liver injury and slightly attenuated inflammatory response, thereby prolonged the survival of the mice. Targeting MIF may be an important strategy to protect the liver from injury during sepsis.

It is noted that elevated serum amylase levels suggesting pancreatic damage has an association with prognosis in PQ patients. This study aimed to determine whether PQ can cause pancreatic damage. The two conventional models (intragastric infusion (iG) and intraperitoneal injection (iP)) may exhibit different effects on the pancreas depending on whether or not they pass through the digestive tract. In this study, the rats were divided into four groups: the intragastric infusion group (PQ-iG, n = 45), intraperitoneal injection group (PQ-iP, n = 53), normal control group 1 (NC-iG, n = 6) and normal control group 2 (NC-iP, n = 6). Pancreatic damage was compared between groups using serum amylase activity assay, hematoxylin and eosin (H&E) staining, TUNEL assay, and transmission electron microscopy (TEM). Serum amylase levels in group PQ-iG were significantly higher than in group PQ-iP (p < 0.05). Examination of the H&E sections showed damage to the pancreas. Both experimental groups were displayed inflammatory infiltration within 9 h of PQ treatment. After 9 h, patchy necrosis was observed in group PQ-iP, when inflammatory infiltration was still the dominant pathology. Necrosis appeared and gradually worsened in group PQ-iG, in which necrosis was the dominant pathology. The TUNEL assay showed significantly higher numbers of apoptotic cells in the pancreas of PQ-groups than in the control NC- groups (p < 0.05). TEM showed expansive endoplasmic reticulum lumens and mitochondria swelling in the pancreas of the PQ-groups. It is concluded that both methods of modeling could cause pancreatic damage and the type and degree of damage would change over time. Note that pancreatic damage in group PQ-iG was more severe than that in group PQ-iP. Therefore, clinical practitioners should pay close attention to pancreatic damage caused by PQ, especially when the route of PQ administration was oral.

Background: SARS-CoV-2 is a newly discovered virus, leading COVID-19 a global threaten nowadays. Case Presentation: The first case of a patient with a thoracic aortic aneurysm (TAA) that became infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported here. The patient died suddenly from a ruptured aorta 19 h after hospital admission. Conclusion: COVID-19 patients with TAA should attract the highest vigilance as COVID-19 might expedite the process of TAA rupture through cytokine storm syndrome, leading to rapid death with little or no warning signs.

Background Patients with cervical spinal cord injuries (CSCIs) may be required to undergo tracheostomy. However, in patients undergoing anterior cervical fusion (ACF), percutaneous dilational tracheostomy (PDT) may be delayed given the risk of cross-contamination. We aimed to evaluate the risk of surgical site infection (SSI) in early PDT in patients with traumatic CSCI after ACF. Methods All trauma patients admitted to the intensive care unit from 2008 to 2018 were retrospectively analyzed. Patients with CSCIs who underwent both ACF and PDT were identified, with or without posterior cervical fusion. Cases were classified as having undergone early PDT (≤4 days after ACF) versus late PDT (>4 days after ACF). Propensity scores were matched, and outcomes were compared between matched groups to reduce confounding by indication. Results From a total of 133 enrolled patients, a well-balanced propensity-matched cohort of 68 patients was defined. On the basis of the comparison of outcomes after matching, no significant difference in SSI was observed between both groups. There was no patient with SSI in the early PDT group (0%), whereas there were 2 SSI patients (5.9%) in the late PDT group (P = 0.493): The tracheostomy site was involved in 1, and the posterior approach site was involved in the other. Early PDT was associated with a shorter duration of mechanical ventilation (P = 0.042). There were no significant differences in the length of intensive care unit stay and hospital mortality between groups. Conclusions Early PDT within 4 days after ACF did not increase the risk of SSI compared with late PDT in patients with traumatic CSCIs.

Background: Chinese emergency medical staff have great mental and work pressure in fighting the coronavirus disease 2019 (COVID-19) pandemic, and it is necessary to understand the prevalenece and influencing factors for depression. Methods: A cross-sectional national survey of general emergency medical staff who were on duty and participated in COVID-19 anti-pandemic from November 2019 to April 2020 was conducted and we used the scale of Patient Health Questionnaire-9 (PHQ-9) to assess depression symptom. Univariate analysis and multivariable logistic-regression models assessed for the associations of influencing PHQ-9 scores. Results: 6588 emergncy medical staff from 1060 hospitals responded to the survey. The average PHQ-9 score of all medical staff was 10.94±5.1. We use PHQ-9≥10 as the cut-off value to define major depression, the prevalence of major depression was 57.60%.The results of univariate analysis showed that demographic factors (gender, age, occupation, relationship status, living with childen ≤16 years-old or adults≥70 years- old), work factors (direct contact with confirmed COVID-19 patients or working in an isolation unit with COVID-19 patients), and forced isolation in the hospital all had an increased risk of major depression. In addition, multivariate logistic regression analysis indicated that main factors associated with major depression symptom were direct contact with confirmed COVID-19 patient (OR 1.153), working in a COVID-19 isolation ward (OR 1.366), age between 31-45 years old (OR 1.139), and living with children ≤16 years old (OR 1.126) or adults≥70 years old (OR 1.325). Working in Hubei province (the epicenter of the outbreak) during COVID-19 had no correlation with depression. Conclusion: Chinese emergency medical staff experienced depression burden during COVID-19 period, particularly, those aged 31-45,those working in isolation unit COVID-19, those living with children or older people These results reinforce the value of effective, targeted staff support during the COVID-19 or future outbreaks. Funding Statement: None. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study has been approved by the Ethics Committee of Peking Union Medical College Hospital, and all the participants provided informed consent.

Background: Chinese emergency medical staff have great mental and work pressure in fighting the coronavirus disease 2019 (COVID-19) pandemic, and it is necessary to understand the prevalenece and influencing factors for depression. Methods: A cross-sectional national survey of general emergency medical staff who were on duty and participated in COVID-19 anti-pandemic from November 2019 to April 2020 was conducted and we used the scale of Patient Health Questionnaire-9 (PHQ-9) to assess depression symptom. Univariate analysis and multivariable logistic-regression models assessed for the associations of influencing PHQ-9 scores. Results: 6588 emergncy medical staff from 1060 hospitals responded to the survey. The average PHQ-9 score of all medical staff was 10.94±5.1. We use PHQ-9≥10 as the cut-off value to define major depression, the prevalence of major depression was 57.60%.The results of univariate analysis showed that demographic factors(gender, age, occupation, relationship status, living with childen ≤16 years-old or adults≥70 years- old), work factors (direct contact with confirmed COVID-19 patients or working in an isolation unit with COVID-19 patients), and forced isolation in the hospital all had an increased risk of major depression. In addition, multivariate logistic regression analysis indicated that main factors associated with major depression symptom were direct contact with confirmed COVID-19 patient (OR 1.153), working in a COVID-19 isolation ward (OR 1.366), age between 31-45 years old (OR 1.139), and living with children ≤16 years old(OR 1.126) or adults≥70 years old (OR 1.325). Working in Hubei province (the epicenter of the outbreak) during COVID-19 had no correlation with depression. Conclusion: Chinese emergency medical staff experienced depression burden during COVID-19 period, particularly, those aged 31-45,those working in isolation unit COVID-19, those living with children or older people These results reinforce the value of effective, targeted staff support during the COVID-19 or future outbreaks. Funding Statement: The authors state that there is no funding for this article. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: The study has been approved by the Ethics Committee of Peking Union Medical College Hospital, and all the participants provided informed consent.

Background Macrophage migration inhibitory factor (MIF) is an important pro-inflammatory cytokine implicated in sepsis, rheumatoid arthritis and other diseases. However, the role of MIF in acute pancreatitis (AP) remains unclear. This study aims to explore the role of MIF in the pathogenesis of AP using MIF−/− mice (referred to as KO) and the biological effects of pharmacological inhibition of MIF in l -arginine induced AP. Methods AP was induced in C57BL/6 wild-type (referred to as WT) and KO mice by administration of l -arginine. The severity of AP was assessed by serum analysis of amylase and lipase, and of these pro-inflammatory cytokines TNF-α and IL-1β. Histological hematoxylin and eosin (H&E) and immunohistochemical staining of pancreatic tissues were examined for inflammation and expression of pro-inflammatory mediators. We also investigated the biological effects of pharmacological inhibition of MIF activity using ISO-1((S,R)-3-(4-hydroxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester). Results At 72 h after the induction of AP with l -arginine, significantly lower levels of serum amylase, lipase, TNF-α, and IL-1β were observed in KO mice when compared with WT controls. Histological examination further showed protective effects against pancreatic tissue damage and inflammation, with pancreatic expression of TNF-α, IL-1β and NF-κB p65 markedly reduced. Pharmacological inhibition of MIF activity with ISO-1 markedly mirrored the protective effect seen in the KO AP model providing further evidence that MIF is involved in the pathogenesis of AP. Conclusion Our data provided strong evidence for the participation of MIF in the pathogenesis of AP and subsequent inflammatory response. The genetic ablation of MIF or its inhibition with pharmacological agents significantly ameliorated the severity of AP.