Xiao-Ming Gao

This study evaluated the effectiveness of non-invasive ultrasound technology in monitoring pulmonary edema in a mouse model of acute lung injury (ALI). Male C57BL/6J mice were instilled through the trachea with lipopolysaccharide (LPS, 5 mg/kg, single dose) to induce ALI. The change in B-lines (an ultrasound sign) were monitored using the Vevo 3100 system and the lung ultrasound (LUS) score was generated to quantify the severity of edema, meanwhile lung function was assessed by whole-body plethysmography (WBP) and the progression of ALI was tracked by lung weight and histopathological analysis. LUS detection revealed that non-converging B-lines appeared on the first day, followed by an increase in the number of B-lines that began to converge, peaking on the day-3 and then the number of B-lines decreased, almost disappearing by the 11 days after LPS intervention. Significant changes in lung functional parameters were recorded during 6–24 h with most parameters returning to baseline levels at day-3. Morphological and weight assessments of the lung showed that most severe lung congestion and increased weight at day-3 and returning to normal by 11 days. Histopathological examination unveiled that LPS-induced inflammation was characterized by increased cellular infiltration, thickening of alveolar septa, vascular congestion, and atelectasis, which were most severe on days 3–5 and then gradually improved. A positive correlation between LUS score and the lung injury index (r = 0.783, P < 0.001) or the lung weight-to-tibial length ratio (r = 0.695, P < 0.001) was observed, reflecting a sensitivity of LUS to the severity of edema. In addition, at 24 h following LPS intervention, the LUS score was also positively or negatively correlated with a series of lung functional indices. In conclusion, the study demonstrated that LUS is an effective, reliable and non-invasive tool for monitoring pulmonary edema in a mouse model of ALI. The significant correlations between LUS scores with various pathophysiological parameters, highlight its potential in assessing the severity of ALI in mice.

High incidence of cardiac rupture in murine myocardial infarction (MI) model leads to a substantial loss before the study end-point. Selecting animal models with varying degrees of injury for different research purposes is crucial for cardiovascular research. Male C57 mice were subjected to ischemia/reperfusion (I/R) or permanent occlusion (MI) injury. The incidence of cardiac rupture, degree of myocardial injury, inflammatory responses, left ventricular (LV) remodeling and infarct myocardium healing were examined. Compared to MI mice, early reperfusion (1, 2 and 4h I/R) completely prevented cardiac rupture, while delayed reperfusion (12h and 24h I/R) significantly reduced incidence of cardiac rupture to 5.7% and 8.6%, respectively. In the acute phase, prolonged ischemia increased infarct size, myocyte apoptosis, and both systemic and regional inflammatory responses. These changes correspond to enhanced MMP-9 activity and a weakening of the tensile strength of the infarcted myocardium. Following ischemic insult, early reperfusion was associated with less extent of myocardial injury, inflammatory response and adverse cardiac remodeling, whereas, delayed reperfusion and MI groups exhibited severe myocardial damage and remodeling. Furthermore, both early and delayed reperfusion were associated with increased infiltration of type 2 macrophages and proliferation of endothelial cells during the early healing phase, thereby facilitating healing of the infarct myocardium. Delayed reperfusion resulted in a comparable and substantial degree of cardiac remodeling but with a lower risk of cardiac rupture in comparison with MI model. This feature makes it a feasible model for cardiac ischemia research.

Objective Prognostic nutritional index (PNI) is an index for assessing nutritional and immune status. The aim of this study is to investigate the predictive value of PNI for long-term major adverse cardiac and cerebrovascular events (MACCE) in ST-segment elevation myocardial infarction (STEMI) patients with type 2 diabetes mellitus (T2DM). Design, setting and participants This retrospective cohort study analysed 1582 STEMI patients with T2DM who underwent percutaneous coronary intervention from January 2015 to June 2023 in Urumqi, China. Patients were followed up for MACCE. Primary and secondary outcome measures The primary endpoint was new-onset MACCE including all-cause death, non-fatal MI and non-fatal stroke. Results This study ultimately included 1582 patients for analysis with a median follow-up period of 48 months (IQR: 24–84 months) and 282 patients (17.8%) developed MACCE. Of them, 138 (8.7%), 84 (5.3%) and 60 (3.8%) patients developed all-cause death, a non-fatal MI and a non-fatal stroke, respectively. Incidences of MACCE and all-cause death conversely correlated with PNI. Kaplan-Meier curves showed a significant difference in all components of MACCE between PNI quartiles (pConclusions PNI, a simple and easily obtainable index, was independently associated with MACCE and all-cause death in this study. Lower PNI levels were significantly linked to an increased risk of long-term MACCE, especially in male, elderly patients and those with higher glycosylated haemoglobin and low- density lipoprotein cholesterol levels.

The rising prevalence of hypertension underscores the urgent need for effective management strategies. While niacin-based medications and supplements have shown promise in improving outcomes among patients with hypertension, the impact of dietary niacin intake on prognosis remains an area requiring further investigation. Using data from the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2016, this study examined the association between dietary niacin intake and mortality risk among 13,237 individuals with hypertension. During a median follow-up of 103 months, 3,151 participants (23.80%) died from all causes, and 864 (7.89%) died from cardiovascular diseases. In multivariable-adjusted Cox proportional hazards models, dietary niacin intake was independently associated with a lower risk of both all-cause mortality (HR = 0.993, 95% CI: 0.986–1.000, p = 0.036) and cardiovascular mortality (HR = 0.984, 95% CI: 0.971–0.997, p = 0.017). Niacin intake was categorized into quartiles: Q1 (< 15.5 mg/day), Q2 (15.5–21.1 mg/day), Q3 (21.1–28.2 mg/day), and Q4 (> 28.2 mg/day). Cox regression analysis indicated that participants in the Q3 group had a significantly lower risk of all-cause mortality compared to those in Q1 (HR = 0.788, 95% CI: 0.657–0.944, p = 0.010). Moreover, restricted cubic spline (RCS) analysis revealed a U-shaped association between dietary niacin intake and all-cause mortality (P for nonlinearity = 0.016). These findings highlight the potential benefits of dietary niacin in reducing mortality risk among hypertensive individuals and suggest that moderate increases in dietary niacin intake may represent a feasible strategy for reducing mortality risk in this population.

The present study was aimed to investigate whether Gensini score or SYNTAX score was a valuable tool to predict in-stent restenosis (ISR) in coronary artery disease (CAD) patients with drug-eluting stents (DES) implantation. A retrospective case-control study and a validating retrospective cohort study were designed. All subjects’ information was collected from the First Affiliated Hospital of Xinjiang Medical University. A total of 916 patients were enrolled in the case-control study, and 961 subjects were included in the retrospective-cohort study. In the case-control study, significant differences were observed between the ISR and non-ISR groups regarding baseline characteristics and clinical examinations, including waist circumference, systolic blood pressure, blood glucose levels, ApoA1 levels, left ventricular ejection fraction, lesion vessels, Gensini score, and SYNTAX score (all P < 0.05). All parameters showing significant differences were also associated with ISR (all P < 0.05). However, after adjustment for confounders, both Gensini score [tertile 3 vs. tertile 1 with OR 95%CI: 15.61 (5.37–45.39)] and SYNTAX score [high risk ≥ 33 vs. low risk ≤ 22 with OR 95%CI 12.61 (5.14–30.94)] were still independently associated with ISR. Furthermore, Gensini score [AUC 95%CI: 0.81 (0.78–0.84)] and SYNTAX score [AUC 95%CI: 0.76 (0.72–0.79)] showed a moderate ability to predict ISR. The predictors were further verified in a cohort validation study, which confirmed that the Gensini score was a better predictor for ISR than SYNTAX score, with an AUC and 95%CI of 0.67 (0.60–0.73) and 0.53 (0.46–0.60), respectively. Gensini score showed a higher capability to predict ISR than SYNTAX score in CAD patients with DES implantation. SYNTAX score may also be a useful tool for assessing the risk of ISR in patients with multivessel lesions.

Purpose To investigate the protective effect and mechanism of enhanced expression of endogenous macrophage migration inhibitory factor (MIF) on cardiac ischemia–reperfusion (I/R) injury. Methods A recombinant double-stranded adeno-associated virus serotype 9 with MIF or green fluorescent protein (GFP) genes (dsAAV9-MIF/GFP) was transduced into mice and neonatal rat ventricular myocytes (NRVMs). The models of cardiac 60 min ischemia and 24 h reperfusion and 12 h hypoxia/12 h reoxygenation (H/R) were established in mice and NRVMs, respectively. Infarct size, cardiac remodeling, and related signaling pathways were assessed. Results The dsAAV9 vector demonstrated strong transduction efficacy and cardiac affinity. Cardiac overexpression of MIF led to a 35.3% reduction in infarct size and improved cardiac function following I/R injury. In the dsAAV9-MIF group, the AMP-activated protein kinase (AMPK) signaling pathway was activated, and autophagy was enhanced during the ischemic period. During reperfusion, the extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling pathway was upregulated, leading to reduced cardiac apoptosis. In vitro, transfection with MIF in NRVMs also upregulated AMPK and ERK1/2 signaling during hypoxia and reoxygenation, respectively. Furthermore, MIF overexpression significantly improved autophagy and mitochondrial function, evidenced by an increased LC3-II/I ratio and enhanced mitochondrial membrane potential (ΔΨm), with these effects reversed by the AMPK inhibitor compound C. Additionally, MIF overexpression led to a 60% reduction in the apoptosis rate of cardiomyocytes subjected to H/R and decreased the Bax/Bcl-2 ratio, partially through the ERK1/2 signaling pathway. Conclusion Enhanced endogenous MIF expression via the dsAAV9 vector provides significant cardioprotection against I/R injury by activating the AMPK and ERK1/2 signaling pathways. Our findings suggest that targeting MIF may represent a viable therapeutic strategy for severe and prolonged I/R injury.

Background: The triglyceride-glucose (TyG) index is regarded as an independent predictor of cardiovascular disease consequences and a reliable surrogate measure of insulin resistance (IR). However, the correlation analysis between triglyceride glucose index and heart failure with preserved ejection fraction in patients with essential hypertension remains unknown. Methods: A single-center, retrospective study was conducted with patients diagnosed with essential hypertension at the First Affiliated Hospital of Xinjiang Medical University, from December 2018 to September 2020. Participants were selected based on specific inclusion and exclusion criteria, with their clinical data and laboratory tests collected. The study employed Spearman’s correlation analysis, logistic regression models, restricted cubic spline plots, and receiver operating characteristic (ROC) curves to investigate the relationships between the TyG index and HFpEF. Results: Out of 1,602 enrolled hypertensive patients, 992 were included in the analysis after applying exclusion criteria. Patients were categorized into tertiles based on the TyG index, which showed that patients in the highest tertile had characteristics associated with a higher risk of HFpEF, including age, body mass index (BMI), systolic blood pressure (SBP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and left ventricular mass index (LVMI). A significant, independent association between the TyG index and HFpEF was confirmed, with an odds ratio (OR) of 5.127 (95% CI [3.894–6.856]). Furthermore, an S-shaped nonlinear relationship was observed between the TyG index and the incidence of HFpEF (nonlinear p < 0.001). TyG index (AUC: 0.824, 95% CI [0.795–0.854]), NT-proBNP (AUC: 0.840, 95% CI [0.816–0.864]), and LVMI (AUC: 0.847, 95% CI [0.820–0.875]) showed good predictive ability for HFpEF. In addition, the TyG+LVMI combination demonstrated the strongest predictive ability (AUC: 0.907, 95% CI [0.887–0.927]). Conclusion: The study underscores a significant association between IR, as indicated by the TyG index, and the development of HFpEF in hypertensive patients. It highlights the critical role of metabolic dysfunction in the pathophysiology of HFpEF, advocating for a broader perspective on cardiovascular risk management.