Background: Pulmonary embolism (PE) is the third most common cause of cardiovascular-related deaths globally; however, the causal relationship between gut microbiota and PE remains unclear. This study aimed to explore the impact of gut microbiota on PE.

Methods: This study utilized a 2-sample Mendelian randomization (MR) design to analyze gut microbiota genome-wide association study data from the MiBioGen database and PE data from the FinnGen database. Statistical methods, such as inverse variance-weighted, MR-Egger, weighted median, and weighted modes, were used to investigate the causal relationship between the gut microbiota and PE. Moreover, a sensitivity analysis was conducted to assess the robustness of the results.

Results: MR analysis revealed that gut microbiota genera Intestinimonas (odds ratio [OR]: 0.797; 95% confidence interval [CI]: 0.666-0.952; P = 0.013) and Roseburia (OR: 0.752; 95% CI: 0.575-0.984; P = 0.038) have a protective effect on PE. Conversely, an increased abundance of the phylum Lentisphaerae (OR: 1.217; 95% CI: 1.033-1.434; P = 0.019), class Lentisphaeria (OR: 1.219; 95% CI: 1.010-1.471; P = 0.039), order Gastranaerophilales (OR: 1.209; 95% CI: 1.017-1.437; P = 0.031), order Victivallales (OR: 1.219; 95% CI: 1.010-1.471; P = 0.039), and the genus Ruminococcus gauvreauii (OR: 1.274; 95% CI: 1.015-1.599; P = 0.037) increases the risk of developing PE. Sensitivity analysis indicated no heterogeneity or horizontal pleiotropy.

Conclusion: Seven gut microbiotas, including the phylum Lentisphaerae, class Lentisphaeria, orders Gastranaerophilales and Victivallales, and genera R. gauvreauii, Intestinimonas, and Roseburia, were causally associated with PE. These findings may contribute significantly to the prevention of PE through dietary modifications and microbiome interventions.

Background: Septic shock is a life-threatening disease with high mortality rates, and the relevant hub genes and biomarkers are poorly understood. We aimed to identify hub genes and prognostic biomarkers of mRNAs/lncRNAs in septic shock to rapidly and accurately diagnose infection, identify patients at a high risk of developing septic shock, and predict prognosis.

Methods: Gene expression profiles of 279 patients with septic shock and 100 healthy controls were analyzed using bioinformatics methods. We screened for differentially expressed genes (DEGs), identified hub genes, and investigated the correlations between mRNA/lncRNA expression and disease severity/prognosis. Protein level validation was performed using blood proteomic data from an independent cohort study.

Results: The protein-protein interaction network constructed using upregulated DEGs contained 102 nodes and 222 edges, with LTF, MMP8, MMP9, CEACAM8, CTSG, LCN2, and PRTN3 identified as hub genes. There was a possible association between LCN2 mRNA upregulation and increased severity of septic shock (odds ratio: 1.518; 95% confidence interval: 0.999-2.305; P = 0.050), approaching statistical significance, and BCL2A1 mRNA upregulation correlated with higher mortality risk (odds ratio: 1.178; 95% confidence interval: 1.035-1.341; P = 0.013). No significant prognostic correlation was observed for lncRNAs. The validation cohort confirmed significant upregulation of MMP9, CTSG, LCN2, LTF, and MMP8 proteins in patients with septic shock, with MMP9, LCN2, CTSG, and LTF exhibiting strong diagnostic performance (area under the curve >0.8).

Conclusion: Seven hub genes related to septic shock were identified, including MMP9, LCN2, CTSG, and LTF, which could potentially function as candidate biotargets and biomarkers for the diagnosis and prognostic prediction of septic shock, though further validation is needed. Notably, LCN2 showed a trend toward association with disease severity, while BCL2A1 correlated with mortality risk.

Background: Glucocorticoids (GCs) are widely used in acute and critical illnesses, but long-term and high-dose use of GCs can cause several vascular side effects. However, the underlying mechanisms are not well-understood. Ferroptosis, a novel form of reactive oxygen species (ROS)-dependent cell death, is characterized by intracellular iron accumulation and lipid peroxidation. NADPH oxidase 4 (NOX4) is a major source of ROS. The roles of ferroptosis and NOX4 in GC-induced endothelial injury remain unknown.

Methods: Human umbilical vein endothelial cells (HUVECs) were exposed to varying concentrations of dexamethasone (DEX) to evaluate ferroptosis and NOX4 expression. Further mechanistic studies were conducted using NOX4-overexpressing adenovirus (Ad-NOX4), NOX4 small interfering RNA (siRNA), ferrostatin-1 (FER-1), and erastin.

Results: Our findings demonstrate that DEX induces ferroptosis in HUVECs. Inhibition of ferroptosis with FER-1 prevents DEX-induced reduction in HUVEC viability. Furthermore, DEX treatment increases NOX4 expression in HUVECs, and NOX4 overexpression with Ad-NOX4 promotes ferroptosis. NOX4 knockdown with siRNA suppresses DEX-induced ROS production, lipid peroxidation, and ferroptosis, thereby improving the viability, angiogenesis, and migration capacity of DEX-treated HUVECs. However, the protective effect of NOX4 knockdown is negated by the reactivation of ferroptosis with erastin.

Conclusion: GC-induced endothelial cell ferroptosis occurs through NOX4-mediated ROS production and lipid peroxidation, leading to cell death, impaired angiogenesis, and migration dysfunction. Inhibition of ferroptosis and NOX4 knockdown ameliorate GC-induced endothelial damage and dysfunction.

Background: Diabetes insipidus (DI) usually coexists with hyponatremia in patients with acute spinal cord injury (SCI). However, the incidence of DI after acute SCI has rarely been reported. In this study, we aimed to determine the incidence rates and risk factors for these conditions and explore early detection and intervention strategies.

Methods: Patients with acute SCI who were sequentially admitted to our center between January 2010 and November 2021 were included. Clinical information was extracted from the medical records. Univariate analyses were performed for each potential risk factor. Variables with a P < 0.1 in univariate analysis were included in the multivariate logistic regression analysis, and those with a P < 0.05 were defined as independent risk factors.

Results: The cohort included 317 patients. One hundred ten (34.7%) of the 317 patients with acute SCI developed hyponatremia, and 60 (18.9%) developed DI. The median time to onset of hyponatremia was 5 days (interquartile range [IQR]: 4-6), and the median time to onset of DI was 7 days (IQR: 6-8). Multivariate logistic regression analysis identified a cervical level of injury and a more severe injury (ASIA A) as strong independent risk factors for hyponatremia (both P < 0.001). Among fracture types, only Type C (compared to Type I) was individually associated with hyponatremia (P = 0.038), although the overall fracture-type variable was not significant (P = 0.156). In contrast, for DI, in addition to cervical level and ASIA A injury (both P < 0.001), the fracture-type variable was a significant predictor overall (P < 0.001), with both Type B (P = 0.027) and Type C (P < 0.001) fractures (vs. Type I) being independent risk factors.

Conclusion: We found a high incidence of hyponatremia (34.7%) and DI (18.9%) in patients with acute SCI. Hyponatremia was mainly associated with higher-level and more severe SCI, with an added risk observed in fracture type C, whereas DI was associated with higher-level SCI, more severe injuries, and fracture types B and C. Our study highlights the interconnected nature of hyponatremia and DI as manifestations of acute SCI. Future research should adopt a unified pathophysiological framework that integrates these findings to better understand the underlying mechanisms.