Dexmedetomidine enhances Mitophagy via PINK1 to alleviate hippocampal neuronal Pyroptosis and improve postoperative cognitive dysfunction in elderly rat.

Postoperative cognitive dysfunction (POCD) is a common complication in elderly surgical patients, significantly affecting their quality of life. Dexmedetomidine (Dex), an anesthetic, has shown promise in alleviating POCD, but its underlying mechanism remains unclear. This study aims to explore how Dex improves POCD in aged rats by targeting the PINK1-mediated mitochondrial autophagy pathway, reducing caspase-1/11-GSDMD-induced hippocampal neuronal pyroptosis. Transcriptome sequencing identified 300 differentially expressed genes enriched in the mitochondrial autophagy pathway in Dex-treated POCD rat hippocampal tissue, with Pink1 as a key candidate. In a POCD rat model, Dex treatment upregulated hippocampal PINK1 expression. In vitro experiments using H19-7 rat hippocampal neurons revealed that Dex enhanced mitochondrial autophagy and suppressed neuronal pyroptosis by upregulating PINK1. Further mechanistic validation demonstrated that Dex activated PINK1-mediated mitochondrial autophagy, inhibiting caspase-1/11-GSDMD-induced neuronal pyroptosis. In vivo experiments confirmed Dex's ability to reduce caspase-1/11-GSDMD-dependent hippocampal neuronal pyroptosis and improve postoperative cognitive function in aged rats. Dexmedetomidine improves postoperative cognitive dysfunction in elderly rats by enhancing mitochondrial autophagy via PINK1 upregulation, mitigating caspase-1/11-GSDMD-induced neuronal pyroptosis.

Association of obstructive sleep apnea symptoms with all-cause mortality and cause-specific mortality in adults with or without diabetes: A cohort study based on the NHANES.

BACKGROUND: The association between obstructive sleep apnea syndrome (OSAS) and mortality has not been extensively researched among individuals with varying diabetic status. This study aimed to compare the relationship of OSAS with all-cause and cause-specific mortality in US individuals with or without diabetes based on data from the National Health and Nutrition Examination Survey (NHANES). METHODS: The study included participants from the NHANES 2005-2008 and 2015-2018 cycles with follow-up information. OSAS data (OSAS.MAP10) was estimated from the questionnaire. Hazard ratios (HRs) and the 95% confidence interval (CI) of OSAS for mortality were calculated by Cox regression analysis in populations with different diabetes status. The relationships between OSAS and mortality risk were examined using survival curves and restricted cubic spline curves. RESULTS: A total of 13 761 participants with 7.68 ± 0.042 follow-up years were included. In the nondiabetic group, OSAS.MAP10 was positively associated with all-cause, cardiovascular, and cancer mortality. In individuals with prediabetes, OSAS.MAP10 was positively related to all-cause mortality (HR 1.11 [95% CI: 1.03-1.20]) and cardiovascular mortality (HR 1.17 [95% CI: 1.03-1.33]). The relationship between OSAS.MAP10 and the risk of all-cause mortality and cancer mortality exhibited L-shaped curves in diabetes patients (both with nonlinear p values <.01). Further threshold effect analysis revealed that OSAS was positively related to death risk when OSAS.MAP10 exceeded the threshold scores. CONCLUSION: The relationship between OSAS and mortality differed among participants with or without diabetes. Individualized clinical treatment plans should be developed in clinical practice to reduce the risk of death for patients with different metabolic conditions.

Cardiac involvement in eosinophilic granulomatosis with polyangiitis: acute eosinophilic myocarditis and chronic inflammatory cardiomyopathy.

OBJECTIVES: Currently, cardiac involvement is used to describe all eosinophilic granulomatosis with polyangiitis (EGPA) cardiac problems. However, heterogeneity exists among them. We aimed to depict the disease spectrum of EGPA cardiac involvement and identify high-risk population. METHODS: We included EGPA patients hospitalized in our center from 2012 to 2023 and in public databases. Based on the cardiac enzymes, cardiac magnetic resonance imaging, and endomyocardial biopsy results, the patients were divided into 3 groups: eosinophilic myocarditis (EGPA-EM), chronic inflammatory cardiomyopathy (EGPA-ICM) and EGPA-Control. Their clinical, laboratory, imaging results and prognoses were collected and compared. RESULTS: A total of 193 EGPA patients were included, 118 with cardiac involvement (74 EGPA-EM, 44 EGPA-ICM) and 75 control. Among EGPA-control, EGPA-ICM and EGPA-EM, eosinophil increased (6.12/8.71/10.42 × 109/l, p< 0.01), ANCA positivity decreased (41.33/31.82/14.86%, p< 0.01), and lung involvement reduced (73.33/72.73/43.24%, p= 0.02). In EGPA-EM, cardiac troponin further elevated (0.27 vs 6.00 ng/ml, p< 0.01), ejection fractions decreased (57.79 vs 33.20%, p< 0.01), while more ST-T abnormality was observed (41.89 vs 20.45%, p= 0.02). The prognosis of EGPA-EM was significantly worse, with 14.86% death rate, and 2-year event-free survival rate below 50%. Further, we proposed a LATE-EAST diagnostic score (7 items, 9 points) to discriminate EGPA-EM from EGPA-ICM using 4 points as threshold [AUC 0.85 (95%CI 0.78-0.92), sensitivity 0.78, specificity 0.86]. CONCLUSIONS: We first proposed different subtypes of cardiac involvement in EGPA. Identification and treatment of EGPA-EM needs improvement. LATE-EAST score could recognize the high-risk EGPA-EM effectively. Multi-disciplinary treatment is warranted, immunosuppressive therapy should be given timely and anti-IL-5 antibodies be tested in trials.

Relationship between systemic immune inflammation index and mortality among US adults with different diabetic status: Evidence from NHANES 1999-2018.

OBJECTIVE: To investigate the association between systemic immune inflammation index (SII) and all-cause or cardiovascular diseases (CVDs) mortality in US adults with different diabetic status based on the National Health and Nutrition Examination Survey (NHANES) database. STUDY DESIGN AND SETTING: Adults with follow-up data in the NHANES 1999-2018 cycles were included in this study. The SII was calculated based on blood cells counts (including neutrophils, lymphocytes, and platelets) measured in the laboratory data. According to the quartiles of SII, population were divided into four groups (Q1-Q4). Mortality data was determined by linking NHANES survey participants to the National Death Index records, which collect mortality data and determine their vital status. Cox regression models were also performed to explore the hazard ratio (HR) and the corresponding 95 % confidence interval (95 % CI) of SII related with all-cause and CVDs mortality. In addition, restricted cubic spline was used to explore the nonlinear relationship between SII and mortality. Subgroup analysis and sensitivity analysis were performed to confirm the robustness of our results. RESULTS: In this study, there were 45,454 participants were enrolled (50.43 % females), with a mean age of 47.35 ± 0.19 years. Among of which, 7971 were diabetes patients and 3281 were pre-diabetes. With the mean 9.89 ± 0.08 follow-up years, there were 6935 (15.26 %) deaths occurred. Of which, 1795 deaths were caused by CVDs. The age-adjusted death rates were higher in participants with high SII levels compared to those with low SII levels. Cox regression analysis, after adjusting for covariates, revealed that SII levels were associated with an increased risk of all-cause mortality (HR, 1.02; 95 % CI, 1.02-1.03, P < 0.0001) and CVDs mortality (HR, 1.05; 95 % CI, 1.02-1.08, P = 0.002) in the fully adjusted Model. Moreover, there was a slight increase in HR values with the progression of diabetes status. Restricted cubic spline analysis demonstrated a "U-shaped" relationship between SII and all-cause mortality in diabetic, pre-diabetic and non-diabetic populations (all the P for nonlinear < 0.001). In addition, the relationship between SII and CVDs mortality was also nonlinear in both the pre-diabetic and non-diabetic populations (both P < 0.001). However, there was a linear relationship between SII and cardiovascular mortality in individuals with diabetes (P = 0.528). CONCLUSION: The SII is closely associated with the risk of all-cause and cardiovascular mortality. These associations vary among individuals with different diabetic states. Therefore, monitoring systemic inflammation and SII values is crucial in mitigating the risk of mortality.