Amiodarone is a potent antidysrhythmic agent that can cause potentially life-threatening pulmonary fibrosis. Accumulating evidence has demonstrated that myofibroblast differentiation is related to the pathogenesis of pulmonary fibrosis. In the present study, we treated human embryonic lung fibroblasts (HELFs) with amiodarone, and investigated the relative molecular mechanism of amiodarone-induced pulmonary fibrosis and pathway determinants PD98059 (extracellular signal-regulated kinase (ERK) inhibitor) and SB203580 (p38 mitogen-activated protein kinase (MAPK) inhibitor). Cell proliferation was assessed by Cell Counting Kit-8 (CCK-8). The secretion of collagen Ⅰ was detected by ELISA. The expressions of α-smooth muscle actin (α-SMA), vimentin, phosphorylated ERK1/2 (p-ERK1/2), ERK1/2, phosphorylated p38 MAPK (p-p38), and p38 MAPK were investigated using Western blot analysis. The levels of α-SMA and vimentin were also determined by immunofluorescence and qRT-PCR. We report that amiodarone promoted cell proliferation and collagen Ⅰ secretion, induced α-SMA and vimentin protein and mRNA expression accompanied by increased phosphorylation of ERK1/2 and p38 MAPK, and furthermore, PD98059 and SB203580 remarkably reduced the proliferative response of HELFs compared with amiodarone group and greatly attenuated α-SMA, vimentin and collagen Ⅰ protein production induced by amiodarone. Taken together, our study suggests that amiodarone regulates cell proliferation and myofibroblast differentiation in HELFs through modulating ERK1/2 and p38 MAPK pathways, and these signal pathways may therefore represent an attractive treatment modality in amiodarone-induced pulmonary fibrosis.

The performance of host immune responses biomarkers and clinical scores was compared to identify infection patient populations at risk of progression to sepsis, ICU admission and mortality. Immune response biomarkers were measured and NEWS, SIRS, and MEWS. Logistic and Cox regression models were employed to evaluate the strength of association. IL-10 and NEWS had the strongest association with sepsis development, whereas IL-6 and CRP had the strongest association with ICU admission and in-hospital mortality. IL-6 [HR (95%CI) = 2.68 (1.61-4.46)] was associated with 28-day mortality. Patient subgroups with high IL-10 (≥ 5.03 pg/ml) and high NEWS (> 5 points) values had significantly higher rates of sepsis development (88.3% vs 61.1%; p < 0.001), in-hospital mortality (35.0% vs. 16.7%; p < 0.001), 28-day mortality (25.0% vs. 5.6%; p < 0.001), and ICU admission (66.7% vs. 38.9%; p < 0.001). Patients exhibiting low severity signs of infection but high IL-10 levels showed an elevated probability of developing sepsis. Combining IL-10 with the NEWS score provides a reliable tool for predicting the progression from infection to sepsis at an early stage. Utilizing IL-6 in the emergency room can help identify patients with low NEWS or SIRS scores.

Amiodarone is a high effectiveness anti-arrhythmia agent which is able to induce pulmonary fibrosis. Many studies have shown that the epithelial-mesenchymal transition (EMT) was a significant process in pulmonary fibrosis. So far, there are no studies about whether EMT was associated with amiodarone-induced pulmonary fibrosis, which was therefore explored in this study. In addition, the underlying mechanisms of amiodarone-induced pulmonary fibrosis were examined in vitro. We found the EMT marker (α-SMA) was significantly increased, while the E-cadherin was significantly decreased in adenocarcinomic human alveolar basal epithelial cells (A549) after amiodarone treatment, suggesting that the epithelial cells were an important source of mesenchymal cells. Transforming growth factor beta1 (TGF-β1) was also increased significantly after amiodarone treatment. In conclusion, this study suggested amiodarone could induce pulmonary fibrosis via EMT, and the TGF-β1 may be a key profibrotic cytokine in mechanisms of amiodarone-induced pulmonary fibrosis.

Background: Oxidative Balance Score (OBS) is a tool for assessing the oxidative stress-related exposures of diet and lifestyle. The study aimed to investigate the association between OBS and low muscle mass.Methods: Overall, 6,307 individuals over the age of 18 were assessed using data from the 2011 to 2018 National Health and Nutrition Examination Survey (NHANES). Weighted logistic regression and models were used, together with adjusted models.Results: There was a negative relationship between OBS and low muscle mass [odds ratio (OR): 0.96, 95% confidence interval (CI): 0.94–0.97, p&lt; 0.0001] using the first OBS level as reference. The values (all 95% CI) were 0.745 (0.527–1.054) for the second level, 0.650 (0.456–0.927) for the third level, and 0.326 (0.206–0.514) for the fourth level (P for trend <0.0001). Independent links with low muscle mass were found for diet and lifestyle factors. A restricted cubic spline model indicated a non-linear association between OBS and low muscle mass risk (P for non-linearity<0.05). In addition, the inflection points of the nonlinear curves for the relationship between OBS and risk of low muscle mass were 20.Conclusion: OBS and low muscle mass were found to be significantly negatively correlated. By modulating oxidative balance, a healthy lifestyle and antioxidant rich diet could be a preventive strategy for low muscle mass.

To determine the optimal fluid resuscitation volume in septic patients with acutely decompensated heart failure (ADHF). Septic patients with ADHF were identified from a tertiary urban medical center. The generalized additive models were used to explore the association between fluid resuscitation volume and endpoints, and the initial 3 h fluid resuscitation volume was divided into four groups according to this model: < 10 mL/kg group, ≥ 10 to ≤ 15 mL/kg group, > 15 to ≤ 20 mL/kg group, and > 20 mL/kg group. Logistic and Cox regression models were employed to explore the association between resuscitation volume and primary endpoint, in-hospital mortality, as well as secondary endpoints including 30-day mortality, 1-year mortality, invasive ventilation, and ICU admission. A total of 598 septic patients with a well-documented history of HF were enrolled in the study; 405 patients (68.8%) had sepsis-induced hypoperfusion. Patients with NYHA functional class III and IV were 494 (83.9%) and 22 (3.74%), respectively. Resuscitation volumes above 20 mL/kg (OR 3.19, 95% CI 1.31–8.15) or below 10 mL/kg (OR 2.33, 95% CI 1.14–5.20) significantly increased the risk of in-hospital mortality in septic patients, while resuscitation volumes between 15 and 20 mL/kg were not associated with the risk of in-hospital death in septic patients (OR 1.79, 95% CI 0.68–4.81). In the multivariable Cox models, the effect of resuscitation volume on 30-day and 1-year mortality in septic patients was similar to the effect on in-hospital mortality. Resuscitation volume exceeds 15 mL/kg significantly increased the risk of tracheal intubation, while fluid resuscitation volume was not associated with ICU admission in the septic patients. In septic patients with hypoperfusion, these fluid resuscitation volumes have similar effects on patient outcomes. This association was consistent across the three subgroups with worsened cardiac function, as well as in sensitivity analyses. Our study observed that an initial fluid resuscitation volume of 10–15 mL/kg in the first 3 h was optimal for early resuscitation in septic patients with ADHF, particularly those with worsened cardiac function. These results need to be confirmed in randomized controlled trials with larger sample sizes.