Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. ICU patients with COPD are facing particularly poor outcomes. Existing biomarkers like blood urea nitrogen (BUN) have shown inconsistent prognostic value. Recent evidence suggests the urea-to-creatinine ratio (UCR) may better reflect muscle catabolism and systemic dysfunction in critical illness. However, its clinical role in predicting prognosis for COPD patients needs to be confirmed. This study aimed to investigate the correlation between UCR levels and poor prognosis in ICU patients with COPD. The clinical data of 2,305 COPD patients were retrieved from the database of Medical Information Mart for Intensive Care IV (MIMIC-IV), including demographic information, vital signs upon ICU admission, comorbidities, laboratory test indicators, arterial blood gas analysis results, and disease severity scores. Patients were grouped into U1 group (UCR < 15.71, n = 558), U2 group (15.71 ≤ UCR < 20.57, n = 593), U3 group (20.57 ≤ UCR < 27.575, n = 578), and U4 group (UCR ≥ 27.575, n = 576) based on the quartile levels of UCR measured at ICU admission. The primary endpoint was 90-day mortality. Clinical baseline characteristics and prognostic endpoints were compared across groups. Logistic regression analysis and restricted cubic spline (RCS) analysis were employed to evaluate the correlation between different UCR levels and the poor prognosis of COPD patients. Patients in the higher UCR groups showed an increased rate of mechanical ventilation and significantly higher mortality rates within the ICU, at 28 days, 30 days, and 90 days (all p < 0.001). A logistic regression model, constructed using important feature variables selected by random forest, revealed that patients in the highest UCR quartile (U4 group) had a significantly elevated mortality risk (OR = 1.835, 95
Background. Spinal cord injury (SCI) is a debilitating neurological disorder characterized by complex pathological processes involving dynamic responses of multiple cell types and intricate regulatory networks. Although single-cell RNA sequencing (scRNA-seq) has been employed to dissect cellular heterogeneity in SCI, the activity and regulatory functions of microRNAs (miRNAs) at single-cell resolution remain largely unexplored. Methods. This study utilized the GSE189070 dataset, integrating single-cell transcriptomic data from mouse spinal cord tissues at eight time points: uninjured control and 0.5, 1, 3, 7, 14, 60, and 90 days post-injury. Following quality control, batch correction, and cell-type annotation, miRNA activities across 12 major cell types were computationally inferred using a motif enrichment-based approach. Temporal clustering of miRNA activity was performed with Mfuzz, and subsequent analyses included target gene prediction, functional enrichment, and network construction. Inferred miRNA activity patterns were validated using an independent bulk miRNA sequencing dataset (GSE90452). Key findings were experimentally verified in BV-2 microglial cells and C8-D1A astrocytes using miRNA inhibitors and mimics. Results. We successfully constructed a single-cell transcriptomic atlas and a dynamic computationally inferred miRNA activity landscape during SCI progression. Independent dataset validation confirmed that inferred miRNA activity changes (e.g., mmu-miR-488-3p, mmu-miR-132-3p) were consistent with actual miRNA expression alterations. Our analysis revealed that microglia and macrophages exhibited dynamic miRNA activity patterns closely associated with inflammatory pathways, including TNFA_SIGNALING_VIA_NFKB and TOLL-LIKE RECEPTOR signaling. Cross-cell-type comparison identified 38 common differentially active miRNAs shared between microglia and macrophages, with network analysis revealing coordinated regulation of key inflammatory genes (e.g., Lif, Csf1, Il18rap). In astrocytes, specific miRNAs (e.g., miR-7a-5p, miR-124-3p) were found to regulate apoptotic pathways by targeting Casp3 and Bcl2 family genes. Experimental validation confirmed that miR-130a-3p promotes microglial inflammation, while miR-7a-5p inhibits astrocyte apoptosis under oxidative stress. Conclusion. This study presents a computationally inferred, experimentally validated single-cell-resolution map of miRNA activity dynamics during SCI, revealing potential regulatory networks in key cell types. The concordance between computational inference and independent experimental data supports the biological plausibility of our findings and provides a foundation for further therapeutic exploration.
Global warming is leading to a continuous increase in the incidence of heat-related illnesses, among which heat stroke is the most severe type, characterized by a core body temperature > 40 °C and multiple organ dysfunction syndrome (MODS). The liver, being a thermosensitive organ, acts both as a target of injury and an "amplifier" of inflammation. Its acute injury and failure are significant causes of death in heat stress. This review summarizes the core mechanisms of heat stress-induced liver injury, including direct damage to hepatocytes by hyperthermia, the dual regulatory role of heat shock proteins (HSPs), gut barrier damage leading to endotoxemia and systemic inflammatory response, ischemia–reperfusion injury, and the involvement of various cell death modes such as apoptosis, pyroptosis, and ferroptosis. Clinically, liver injury manifests as a sharp rise in transaminases, abnormal bilirubin metabolism, and coagulation dysfunction, often combined with damage to the heart, brain, kidneys, and other organs, constituting MODS. Current treatments primarily focus on rapid cooling and organ support. Potential strategies include cell death inhibitors, antioxidants, and gut barrier protection. Severe cases may require artificial liver support systems (ALSS) or liver transplantation. Future efforts should delve deeper into the mechanisms of cell death, promote the clinical translation of targeted therapies, and strengthen effective prevention of heat stroke.
Atherosclerosis, a chronic inflammatory disease characterized by lipid accumulation, plaque formation, and calcification within large arteries, remains a leading cause of cardiovascular morbidity. This review integrates emerging evidence on the central role of microRNAs (miRNAs) as master regulators of macrophage biology in atherosclerosis pathogenesis. We highlight how miRNAs orchestrate macrophage polarization (e.g., miR-155 promotes the proinflammatory M1 phenotype; miR-126 facilitates the anti-inflammatory M2 phenotype), inflammatory responses (via NF-κB/TLR signaling), lipid metabolism (through the modulation of CD36 and ABCA1/ABCG1-mediated uptake/efflux), and programmed cell death (through apoptosis, autophagy, and ferroptosis). Therapeutically, targeting miRNA-mediated regulatory networks in macrophages offers unique potential to concomitantly ameliorate lipid accumulation, inflammation, and plaque vulnerability. However, translational challenges-including tissue-specific delivery, miRNA stability, and clinical validation-require innovative solutions such as engineered nanoparticles and combinatorial strategies. Advancing miRNA-based therapeutics may lead to the development of precision interventions for atherosclerosis beyond conventional approaches.
Tinnitus, a prevalent auditory symptom, can significantly impair quality of life, yet no definitive pharmacological interventions exist despite extensive ongoing research into its pathophysiology and treatments. The advent of biomedical engineering has introduced neuromodulation as a pivotal therapeutic approach alongside conventional strategies such as pharmacotherapy and surgery. Through the deployment of invasive and non-invasive techniques, using various modalities including magnetic, electronic, and optical means, neuromodulation aims to regulate neural functions. This has not only led to the refinement of fundamental theories but has also enhanced the optimization of clinical applications. As an emerging and promising intervention, neuromodulation enriches the toolkit available for basic neuroscience inquiry and broadens the spectrum of clinical therapies for conditions affecting the central nervous system, including tinnitus. In this paper, we succinctly review the current understanding of tinnitus mechanisms, discuss the features of diverse neuromodulation technologies, explore their application in tinnitus management, and contemplate prospects for their development in treating tinnitus.
