FGF10 protects against particulate matter-induced lung injury by inhibiting ferroptosis via Nrf2-dependent signaling.

Particulate matter (PM) is considered the fundamental component of atmospheric pollutants and is associated with the pathogenesis of many respiratory diseases. Fibroblast growth factor 10 (FGF10) mediates mesenchymal-epithelial signaling and has been linked with the repair process of PM-induced lung injury (PMLI). However, the pathogenic mechanism of PMLI and the specific FGF10 protective mechanism against this injury are still undetermined. PM was administered in vivo into murine airways or in vitro to human bronchial epithelial cells (HBECs), and the inflammatory response and ferroptosis-related proteins SLC7A11 and GPX4 were assessed. The present research investigates the FGF10-mediated regulation of ferroptosis in PMLI mice models in vivo and HBECs in vitro. The results showed that FGF10 pretreatment reduced PM-mediated oxidative damage and ferroptosis in vivo and in vitro. Furthermore, FGF10 pretreatment led to reduced oxidative stress, decreased secretion of inflammatory mediators, and activation of the Nrf2-dependent antioxidant signaling. Additionally, silencing of Nrf2 using siRNA in the context of FGF10 treatment attenuated the effect on ferroptosis. Altogether, both in vivo and in vitro assessments confirmed that FGF10 protects against PMLI by inhibiting ferroptosis via the Nrf2 signaling. Thus, FGF10 can be used as a novel ferroptosis suppressor and a potential treatment target in PMLI.

MiR-3074-5p suppresses non-small cell lung cancer progression by targeting the YWHAZ/Hsp27 axis.

Non-small cell lung cancer (NSCLC) accounts for more than 80% of lung cancer cases, and the 5-year survival rate of patients remains unsatisfactory. MicroRNAs (miRNAs) are small endogenous noncoding RNAs that are considered essential posttranscriptional regulators of tumorigenesis, including NSCLC. In this study, we aimed to investigate the biological role of miR-3074-5p in NSCLC cells and the underlying molecular mechanisms. We showed that miR-3074-5p expression was decreased in human NSCLC specimens and cell lines. Moreover, miR-3074-5p overexpression inhibited cell proliferation, migration and invasion and induced apoptosis and cell cycle arrest. In addition, miR-3074-5p overexpression not only suppressed tumor growth but also enhanced the antitumor effect of paclitaxel (PTX) on NSCLC cells in vitro and in vivo. A transcriptome sequencing assay revealed genes that were differentially expressed after miR-3074-5p overexpression, and among the genes whose expression levels were most significantly decreased, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ) was a target of miR-3074-5p. The regulatory effect of miR-3074-5p on YWHAZ expression was verified by Western blotting and dual-luciferase reporter assays. The inhibition of A549 cell growth, migration and invasion was reversed by YWHAZ overexpression. Furthermore, we showed that PTX stimulated the expression of the YWHAZ and Hsp27 proteins and promoted the phosphorylation of Hsp27 (at S15 and S78). YWHAZ was confirmed to interact with Hsp27 in A549 cells, and downregulating YWHAZ expression promoted the degradation of the Hsp27 protein. Taken together, these results suggest that the miR-3074-5p/YWHAZ/Hsp27 axis may be a novel therapeutic target for NSCLC treatment.

Association between frailty and acute kidney injury after cardiac surgery: unraveling the moderation effect of body fat through an international, retrospective, multi-cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication after cardiac surgery that significantly affects patient outcomes. Given the limited treatment options available, identifying modifiable risk factors is critical. Frailty and obesity, two heterogeneous physiological states, have significant implications for identifying and preventing AKI. Our study investigated the interplay among frailty, body composition, and AKI risk after cardiac surgery to inform patient management strategies. MATERIAL AND METHODS: This retrospective cohort study included three international cohorts. Primary analysis was conducted in adult patients who underwent cardiac surgery between 2014 and 2019 at Wuhan XX Hospital, China. We tested the generalizability of our findings with data from two independent international cohorts, the Medical Information Mart for Intensive Care IV (MIMIC-IV) and the eICU Collaborative Research Database. Frailty was assessed using a clinical lab-based frailty index (FI-LAB), while total body fat percentage (BF%) was calculated based on a formula accounting for BMI, sex, and age. Logistic regression models were used to analyze the associations between frailty, body fat, and AKI, adjusting for pertinent covariates. RESULTS: A total of 8785 patients across three international cohorts were included in the study. In the primary analysis of 3,569 patients from Wuhan XX Hospital, moderate and severe frailty were associated with an increased AKI risk after cardiac surgery. Moreover, a nonlinear relationship was observed between body fat percentage and AKI risk. When stratified by the degree of frailty, lower body fat correlated with a decreased incidence of AKI. Extended analyses using the MIMIC-IV and eICU cohorts (n=3,951 and n=1,265, respectively) validated these findings and demonstrated that a lower total BF% was associated with decreased AKI incidence. Moderation analysis revealed that the effect of frailty on AKI risk was moderated by the body fat percentage. Sensitivity analyses demonstrated results consistent with the main analyses. CONCLUSION: Higher degrees of frailty were associated with an elevated risk of AKI following cardiac surgery, and total BF% moderated this relationship. This research underscores the significance of integrating frailty and body fat assessments into routine cardiovascular care to identify high-risk patients for AKI and implement personalized interventions to improve patient outcomes.

Patients 60 Years of Age and Older Should Have the Same Chance for Heart Transplantation or Not? / 华中科技大学学报（医学）（英德文版）

Heart transplantation is considered the best treatment modality for advanced heart disease.While old age has conventionally been considered a contraindication for heart transplantation due to the reported adverse effect of advanced age,however donor hearts' shortage continues to stimulate the discussion about the recipient's upper age limit.Our study was based on a retrospective analysis for the results of 52 (18％) patients aged 60 years and older undergoing heart transplantation between May 2008 and December 2015,and these patients were compared with 236 (82％) adult recipients who were younger than 60 years at the time of transplantation and during the same period.In older group,71％ were males with the mean age of 63.38+3.55 years,and in younger group,83.4％ were males with a mean age of43.72±11.41 years (P=0.27).Dilated cardiomyopathy was the most common indication for transplantation among patients in both groups (P=0.147).In older group,the 3-month survival rate was higher than that in younger group (P=0.587),however the 6-month survival rate showed no significant difference (P=0.225).Although the 1-year survival rate was higher in older group (P=0.56),yet the 3-year survival rate between the two groups showed no statistically significant difference (P=0.48).According to our experience among older heart transplant candidates who were 60 years and older,we believe that advanced age should not be an excluding criterion to cardiac transplantation.

Benefit and Safety of Dual Antiplatelet Therapy after Coronary Artery Bypass Grafting for Off-pump CABG: A Systematic Review and Meta-analysis.

Aims: This study aims to evaluate benefit and safety compared dual antiplatelet therapy with single aspirin therapy after coronary artery bypass grafting. Study Design: A systematic review and Meta-analysis. Place and Duration of Study: Medline, Embase, ScienceDirect and Cochrane Library databases were searched for randomized controlled trials or observational studies focusing on anticoagulant therapy after coronary artery bypass grafting until December 2014. Methodology: Endpoints included postoperative mortality, bleeding events, myocardial infraction, stroke, repeat revascularization and graft occlusion. All these endpoints were compared between dual antiplatelet therapy and single aspirin therapy. Newcastle-Ottawa and Jadal scale were used to assess the quality of observational studies and randomized controlled trials respectively. Software R2.15.2 was utilized for Meta-analysis. Results: 15 studies composed of 31,365 patients were included. Compared with single aspirin therapy, dual antiplatelet therapy resulted in reducing risk of vein graft occlusion (OR=0.53, 95%CI 0.36-0.81, P=0.001), but no significant difference for artery graft occlusion (OR=0.91, 95%CI 0.39-2.12, P=0.882), Risk of postoperative mortality (OR=0.57, 95%CI 0.38-0.85, P=0.006) and repeat revascularization (OR=0.15, 95%CI 0.05-0.45, P=0.001) was also reduced. There were no significant difference for MI (OR=0.77, 95%CI 0.55-1.09, P=0.137), Stroke (OR=0.85, 95%CI 0.60-1.19, P=0.330) and bleeding (OR=0.95, 95%CI 0.82-1.09, P=0.465). In subgroup analysis of off-pump CABG, dual antiplatelet therapy reduced risk of graft occlusion (OR=0.49, 95%CI 0.30-0.82, P=0.006), MI (OR=0.28, 95%CI 0.11-0.72, P=0.009), mortality (OR=0.39, 95%CI 0.25-0.60, P<0.001), and did not increase risk of bleeding (OR=0.75, 95%CI 0.55-1.02, P=0.066). Conclusions: Dual antiplatelet therapy reduced risk of postoperative graft occlusion and mortality in the early and late postoperative phase after CABG. It appeared to be more beneficial for off-pump CABG.

Clinical analysis of 63 cases with gastric gastrointestinal stromal tumors / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To analyze the clinicopathological characteristics of gastric gastrointestinal stromal tumors (gastric GISTs) and to explore the diagnosis, treatment and prognosis of gastric GISTs.</p><p><b>METHODS</b>Clinical data of 63 cases with gastric GISTs from January 1997 to May 2007 were analyzed retrospectively. All patients were treated by surgery. All the 63 cases were grouped according to the Fletcher 4-tier system for predicting the aggressiveness of GISTs. Survival was calculated by Kaplan-Meier method. Univariate and multivariate analyses were performed using log-rank analysis and Cox regression model respectively to evaluate the prognostic factors.</p><p><b>RESULTS</b>The accuracy of preoperative ultrasonography, CT and EUS was 72.2%, 81.0% and 94.3% respectively. The diagnostic accuracy of EUS was significantly higher than those of ultrasonography and CT(chi(2)=6.065, P<0.05). Of the 63 gastric GISTs, 31 cases(49.20%) were at fundus. Immunohistochemistry staining revealed that the positive rates of CD117 and CD34 were 88.9% and 95.1% respectively. The 1-, 3- and 5-year total survival rates of 63 patients were 96.4%, 84.7% and 71.7% respectively. Univariate analysis revealed that the differences of Fletcher classification and tumor size were significant. No significant differences in gender, age, mitotic index, immunohistochemistry expression and multi-organ resection existed among the groups. Multivariate analysis demonstrated that Fletcher classification was the independent poor prognostic factor for survival.</p><p><b>CONCLUSIONS</b>The preoperative diagnostic accuracy of EUS is significantly higher than those of ultrasonography and CT. Fletcher classification is reasonable and feasible to evaluate the prognosis of gastric GISTs.</p>