Background: Studies have revealed the association between exosomes and cardiovascular diseases. However, the typical changes of plasma miRNAs in patients with atrial fibrillation (AF) are still controversial, the use of exosomal miRNAs to diagnose and predict the prognosis of AF has not been described.Hypothesis: We hypothesized that there were differences in the exosomal miRNAs between AF and normal sinus rhythm (SR) patients, which might be used as the novel biomarkers to reflect the progression of AF.Methods: miRNAs were isolated from the plasma of patients, and the target genes of differential miRNAs via enrichment analysis to discover potential pathogenesis related to AF. Combined with high‐throughput sequencing results, real‐time PCR was used to verify the relative expression of target miRNAs in patients.Results: This study confirmed that the expression of plasma‐derived exosomal miRNAs between patients with AF and SR were different. Target gene enrichment analysis suggested that the target genes of 20 miRNAs, which were significantly upregulated were mainly enriched in biological processes such as gene expression process, inflammation response, enzyme modification, etc. Meanwhile, mitogen‐activated protein kinase (MAPK), mammalian target of rapamycin (mTOR), and other pathways were highly enriched. The expressions of miR‐92b‐3p, miR‐1306‐5p, and miR‐let‐7b‐3p had differences between patients with AF and SR.Conclusion: These miRNAs and target genes were involved in the process of AF through affecting biological processes such as energy metabolism, lipid metabolism, inflammation, and enzyme activity. It suggested that the exosomal miRNAs might be used as the novel biomarkers to reflect the progression of AF.

Homocysteine (Hcy) and glutathione (GSH) are crucial reduction‑oxidation mediators. The underlying mechanisms governing the effects of Hcy on GSH generation in the progression of alcoholic liver disease has so far received little attention. The present study hypothesized that the antioxidant transcriptional factor nuclear factor (erythroid‑derived 2)‑like 2 (Nrf2) may participate in Hcy‑mediated regulation of GSH production in HepG2 human liver cancer cells. MTT assay was used to study the cytotoxicity of homocysteine, western blot analysis and immunofluorescence staining were used to determine the effect of Hcy on Nrf2 expression. Our data demonstrated that HepG2 cells exposed to exogenous levels of Hcy (0‑100 µM) exhibited elevated GSH levels in a concentration‑dependent manner. Furthermore, 4‑hydroxynonenal (4‑HNE)‑induced cell injury was attenuated by Hcy; however, this protective effect was blocked by the GSH‑production inhibitor buthionine sulfoximine. Hcy treatment was able to induce Nrf2 protein expression in HepG2 cells. Treatment with the Nrf2 activator tert‑butylhydroquinone (0‑100 µM) increased GSH expression in a concentration‑dependent manner; however, Nrf2‑siRNA abolished the Hcy‑induced increase in GSH expression and cellular protection in 4‑HNE‑stressed HepG2 cells. In conclusion, the antioxidant transcriptional factor Nrf2 was demonstrated to mediate the Hcy‑induced increase in GSH expression levels and cellular protection in HepG2 cells.

Traumatic brain injury (TBI) is a severe injury characterized by neuroinflammation and oxidative stress. NAMO (Nicotinamide n-oxide) has anti-inflammatory and inhibits microglial overactivation in neurological disorders. However, the role and mechanism of NAMO in microglial pyroptosis after TBI are unknown. The aim of this study was to investigate the effects of NAMO on TBI and its potential mechanisms through in vivo and in vitro models. In this study, western blot assays were performed by extracting brain tissue mitochondria, and the results showed that NAMO promoted the expression of mitophagy-associated proteins (p62, LC3B, and TOMM20), reduced ROS levels, and inhibited pyroptosis-associated proteins (NLRP3, GSDMD, GSDMD-N, and Caspase-1) and inflammatory cytokines (IL-1β and IL-18). We followed up with immunofluorescence co-localization of GSDMD and IBA 1, which showed that NAMO inhibited microglial pyroptosis. In addition, NAMO promoted neurological recovery after TBI. In vitro experiments showed that NAMO upregulated mitophagy, improved mitochondrial dysfunction, and reduced ROS levels in microglia following lipopolysaccharide (LPS) + adenosine triphosphate (ATP) stimulation in HMC3 cells. We also found that NAMO inhibited pyroptosis-related proteins. To further illustrate whether NAMO affects pyroptosis through mitophagy, we applied the mitophagy inhibitor Mdivi-1 in both in vivo and in vitro models. The results showed that Mdivi-1 reversed NAMO's inhibitory effect on microglial pyroptosis. Taken together, our findings demonstrate that NAMO improves neurological recovery by inhibiting microglial pyroptosis through upregulation of mitophagy, suggesting that NAMO could be a potential therapeutic agent for TBI.

To determine whether individualized fraction of inspired oxygen (iFiO₂) improves pulmonary atelectasis after elective laparoscopic colorectal surgery relative to 60 % FiO₂. This was a single-center, prospective, randomized study. This study was conducted in a single tertiary care hospital in China. A total of 84 eligible inpatients who underwent elective laparoscopic colorectal surgery between August 2021 and May 2022 were included in the study. The patients were randomly assigned to receive either a fixed fraction of inspiration oxygen (fFiO₂ group) or individualized FiO₂ based on physiological SpO₂ (iFiO₂ group). The primary outcome was the lung ultrasound score (LUS) at 30 min after extubation. Secondary outcomes included the length of hospital stay, admission to the intensive care unit, the length of post-anesthetic care unit stay, the ratio of lung capacity on the third day after surgery compared with before surgery, the incidence of nausea and vomiting, and surgical site infections after surgery. Additionally, the airway plate pressure, airway peak pressure, pulmonary dynamic compliance, PaO₂, oxygenation index, alveolar-arterial oxygen tension gradient (A-aDO₂), and pulmonary shunt fraction (Qs/Qt) were considered. The LUS was significantly lowered in the iFiO₂ group (5 [4, 7]) compared with the fFiO₂ group (8 [4, 10]) (P = 0.03). Based on the criterion for determining atelectasis, 25 patients (62.5 %) in the fFiO₂ group experienced significant atelectasis compared with 15 patients (37.5 %) in the iFiO₂ group (P = 0.025). At the end of surgery, PaO₂, A-aDO₂, and Qs/Qt were significantly reduced in patients in the iFiO₂ group compared with those in the fFiO₂ group. The use of iFiO₂ during operation significantly reduces the LUS and pulmonary atelectasis in patients undergoing laparoscopic colorectal surgery under general anesthesia. ChiCTRT2100049615.

Traumatic brain injury (TBI) is one of the major causes of morbidity and mortality among adults. Blood brain barrier (BBB) damage is one of the main factors of secondary injury following TBI. However, whether iPLA2β activity affected vascular endothelial cells after TBI and its mechanism remains unclear. To investigate this, Feeney's weight-drop model in rats and H₂O₂ induced oxidative stress model in bEnd.3 cells were established, s-BEL (an inhibitor of iPLA2β) and ATP (an agonist of iPLA2β) were used for treatment. Behavioral assessments, BBB permeability, Immunofluorescence, Transmission Electron Microscopy, ROS, etc. are applied in the research. We found that TBI lead to autophagy in cerebral vascular endothelial cells of rats. s-BEL exacerbated ZO1 and Occludin damage, as well as BBB disruption through autophagy, whereas ATP protected the BBB from damage. Inhibiting autophagy reduced ZO1 and Occludin damage caused by decreased iPLA2β activity in bEnd.3. Inhibiting p38 MAPK could alleviate excessive autophagy and the damage to ZO1 and Occludin. In conclusion, the decreased iPLA2β activity following TBI in rats leads to increased autophagy in vascular endothelial cells and BBB disruption. The iPLA2β/p38 MAPK pathway could inhibit endothelial cells autophagy, alleviate tight junction damage and BBB disruption, thereby improving brain injury.

Introduction: A growing body of evidence suggests that alcohol use disorders coexist with depression. However, the causal relationship between alcohol consumption and depression remains a topic of controversy.Methods: We conducted a two-sample two-way Mendelian randomization analysis using genetic variants associated with alcohol use and major depressive disorder from a genome-wide association study.Results: Our research indicates that drinking alcohol can reduce the risk of major depression (odds ratio: 0.71, 95% confidence interval: 0.54~0.93, p = 0.01), while increasing the frequency of drinking can increase the risk of major depression (odds ratio: 1.09, 95% confidence interval: 1.00~1.18, p = 0.04). Furthermore, our multivariate MR analysis demonstrated that even after accounting for different types of drinking, the promoting effect of drinking frequency on the likelihood of developing major depression still persists (odds ratio: 1.13, 95% confidence interval: 1.04~1.23, p = 0.005). Additionally, mediation analysis using a two-step MR approach revealed that this effect is partially mediated by the adiposity index, with a mediated proportion of 37.5% (95% confidence interval: 0.22 to 0.38).Discussion: In this study, we found that alcohol consumption can alleviate major depression, while alcohol intake frequency can aggravate it.These findings have important implications for the development of prevention and intervention strategies targeting alcohol-related depression.