Fibroblast growth factor (FGF)21 is a peptide hormone that improves mitochondrial function and energy metabolism, and the deficiency of its co‑receptor β‑klotho (KLB) causes decreased FGF21 sensitivity. The present study examined whether the cardiac delivery of plasmids containing the KLB gene via ultrasound‑targeted microbubble destruction (UTMD) enhances the efficacy of FGF21 against heart failure post‑acute myocardial infarction (AMI). For this purpose, the levels of FGF21 in patients and rats with heart dysfunction post‑infarction were determined using ELISA. Sprague‑Dawley rats received the 3X UTMD‑mediated delivery of KLB@cationic microbubbles (KLB@CMBs) 1 week following the induction of AMI. Echocardiography, histopathology and biochemical analysis were performed at 4 weeks following the induction of AMI. The results revealed that patients with heart failure post‑infarction had higher serum FGF21 levels than the healthy controls. However, the downstream signal, KLB, but not α‑klotho, was reduced in the heart tissues of rats with AMI. As was expected, treatment with FGF21 did not substantially attenuate heart remodeling post‑infarction. It was found that decreased receptors KLB in the heart may result in the insensitivity to FGF21 treatment. In vivo, the UTMD technology‑mediated delivery of KLB@CMBs to the heart significantly enhanced the effects of FGF21 administration on cardiac remodeling and mitochondrial dysfunction in the rats following infarction. The delivery of KLB to the heart by UTMD and the administration of FGF21 attenuated mitochondrial impairment and oxidative stress by activating nuclear factor erythroid 2‑related factor 2 signals. On the whole, the present study demonstrates that the cardiac delivery of KLB significantly optimizes the cardioprotective effects of FGF21 therapy on adverse heart remodeling. UTMD appears a promising interdisciplinary approach with which to improve heart failure post‑myocardial infarction.

Background: Non-carbon monoxide (non-CO) poisoning remains a significant global public health issue, contributing to considerable morbidity and mortality. However, there is a lack of comprehensive analysis regarding the global burden and trends of non-CO poisoning.Methods: Data from the Global Burden of Disease (GBD) 2021 study were used to assess the global, regional, and national prevalence, mortality, and disability-adjusted life years (DALYs) associated with non-CO poisoning from 1990 to 2021. Descriptive statistical methods were applied to assess global, regional, and national trends in non-CO poisoning burden, with estimates of prevalence, mortality, and DALYs. Smoothing splines models were used to examine the relationship between non-CO poisoning burden and the Socio-Demographic Index (SDI).Results: In 2021, global non-CO poisoning accounted for 3.58 million prevalent cases (ASPR: 43.34/100,000), 27.26 thousand deaths (ASDR: 0.35/100,000), and 1.65 million DALYs (ASR: 21.72/100,000), with respective declines of 43.9, 38.9, and 43.5% since 1990. The burden of non-CO poisoning varies significantly across countries and regions, overall, the burden of non-CO poisoning shows a negative correlation with the SDI, with regions and countries with lower SDI values experiencing higher rates of poisoning-related harm. Children under 5 years old and the older adult bear a higher disease burden, with males generally experiencing higher disease burden than females.Conclusion: Although the global burden of non-CO poisoning has decreased, low- and middle-income countries (LMICs), especially those with lower SDI, continue to experience a disproportionately high burden. Future research should focus on agent-specific epidemiology, improving data collection in LMICs, and examining the impact of agricultural and environmental exposures. Targeted interventions for vulnerable populations, such as children and the older adult, as well as the integration of mental health considerations into prevention strategies, are essential for reducing the global burden.

While significant evidence has linked various biomarkers to cardiovascular risk, the role of the red cell distribution width to albumin ratio (RAR) in predicting coronary heart disease (CHD) remains underexplored. This cross-sectional study utilized data from 48,928 participants from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2018. The exposure variable was RAR, calculated as the ratio of red cell distribution width to serum albumin levels. CHD was determined based on self-reported data. Multivariate logistic regression was used to examine the relationship between RAR and CHD, adjusting for potential confounders, with stratified analyses by sex, diabetes status, and hypertension status. The mean age of participants was 49.64 ± 18.17 years, with a mean RAR of 3.15 ± 0.51. In the fully adjusted model (Model 3), an increase in RAR was associated with an increased risk of CHD (OR = 1.31, 95% CI: 1.13, 1.51, P < .001). Stratified analysis revealed that higher RAR quartiles were associated with higher CHD risk, especially in females and those with diabetes. But no significant interaction was found between RAR and gender or diabetes status on CHD risk. Our study suggests that RAR is associated with an increased risk of CHD, particularly at higher quartiles. While RAR may help clinicians identify individuals at elevated risk for CHD, further longitudinal studies and mechanistic investigations are needed to better understand its predictive value and clinical applicability.

A clinically useful immune biomarker could potentially assist clinicians in their decision making. We stimulated T-cell proliferation to secret interferon gamma (IFN-γ) by phytohemagglutinin, and then measured the production of IFN-γ (mitogen value [M value]). We aimed to determine the relationship between the M value, clinical severity, and outcomes of diseases. In all, 484 patients admitted to intensive care units were enrolled in this retrospective study. The Acute Physiology and Chronic Health Evaluation II (APACHE II) scores were collected within the first 24 hours. M value, C-reaction protein (CRP), procalcitonin (PCT), erythrocyte sedimentation rate (ESR), and routine blood tests were analyzed and collected during the study. When APACHE II scores were greater than 15 and M values were less than 6, the hospital mortality rose in a straight line. There was an inverse correlation between APACHE II score and M value (r _s = −0.212, P < .001). There was a positive correlation between M value and lymphocyte numbers (b’ = 0.249, P < .001); however, there was an inverse correlation between M value and WBC (b’ = −0.230, P < .001), and ESR (b’ = −0.100, P = .029). Neurological diseases had the greatest influence on APACHE II scores (b’ = 10.356, P < .001), whereas respiratory diseases had the greatest influence on M value (b’ = 1.933, P < .001). Furthermore, in the respiratory system, severe pneumonia had a greater influence on M value. Taking the APACHE II score as the gold standard, the area under the curve of M was 0.632 (95% confidence interval [CI] 0.575–0.690, P < .001), PCT was 0.647 (95% CI 0.589–0.705, P < .001), CRP was 0.570 (95% CI 0.511–0.629, P = .022), and ESR was 0.553 (95% CI 0.494–0.612, P = .078). Divided by M value = 5, the positive predictive value of the M value is 37.22% (115/309) and negative predictive value is 75.43% (132/175). The results show that the M values, PCT, and CRP were better than ESR to predict the severity of diseases. The number and proportion of lymphocytes also affected the result of the M value. To a certain extent, the M value may be a clinically useful immune biomarker, which may help clinicians objectively evaluate the severity of diseases, especially in the respiratory system.