Yuqian Guo

Background: Sepsis, a life-threatening condition caused by infection, induces dysregulated immune responses. Lactylation is a lactate-derived posttranslational modification with roles in various cellular processes. We investigated lactylation levels in the immune cells of patients with sepsis and evaluated their association with disease progression. Methods: In this prospective cohort study, blood samples were collected on days 1 and 3 from 58 intensive care unit patients, including critically ill controls and sepsis patients (survivors and nonsurvivors). Biochemical and clinical data were analyzed, and immune cells were isolated to measure pan-lysine lactylation (Pan Kla), H4K5la, and H3K56la levels using flow cytometry. Results: Patients with sepsis exhibited significantly elevated neutrophil H4K5la levels compared with critically ill controls on day 1 (231.6 [174.9–361.9] vs. 127.5 [69.4–168.9] mean fluorescence intensity [MFI], P < 0.0001); similar trends were observed in monocytes, B cells, and T cells. Multivariate analysis identified neutrophil H4K5la levels as an independent predictor of sepsis. The combination of day 1 neutrophil H4K5la and C-reactive protein levels improved diagnostic performance (area under the receiver operating characteristic curve = 0.902 [95% confidence interval, 0.795–0.964]). On day 3, nonsurvivors showed lower lactylation levels than survivors (monocyte Pan Kla: 79.8 [54.9–106.1] vs. 133.2 [112.3–259.2] MFI, P = 0.0334; T-cell H3K56la: 15.5 [8.2–28.1] vs. 37.2 [23.9–71.4] MFI, P = 0.0143). Conclusions: Immune cell lactylation may serve as a biomarker for sepsis progression. The combination of neutrophil H4K5la and C-reactive protein enhances early diagnostic accuracy; reduced lactylation on day 3 may indicate poor prognosis.

Background/Objectives: Left ventricular diastolic dysfunction (LVDD) and elevated left ventricular filling pressure (LVFP) are strong predictors of clinical outcomes across various populations. However, their diagnostic utility in embolic stroke of undetermined source (ESUS) remains unclear. We hypothesized that LVDD with elevated LVFP (based on echocardiography) was more likely to be prevalent in ESUS compared to non-cardioembolic stroke (NCE) and to be associated with atrial fibrillation (AF) on follow-up monitoring. Methods: This is a single-center retrospective study that included adult patients with a diagnosis of acute ischemic stroke between January 2016 and June 2017. LV function was assessed by inpatient transthoracic echocardiogram (TTE), and stroke etiology was adjudicated by the neurologist per the consensus criteria. Patients with cardioembolic stroke and those with indeterminate diastolic function on TTE were excluded. Baseline patient characteristics and clinical variables were compared among patients with and without LVDD and elevated LVFP. Multivariable regression models were used to assess the associations between diastolic dysfunction, ESUS, and AF detection in ESUS patients. Results: We identified 509 patients with ESUS and NCE stroke who had reported diastolic function. The mean age was 64.19 years, 45.19% were female, and 146 had LVDD with available LVFP data. LVDD was not associated with ESUS (adjusted OR: 1.43, 95% CI: 0.90–2.27, p = 0.130) or atrial fibrillation (AF) detection on cardiac monitoring (adjusted OR: 1.88, 95% CI: 0.75–4.72, p = 0.179). However, LVDD with elevated LVFP was borderline associated with ESUS (adjusted OR: 2.17, 95% CI: 0.99–4.77, p = 0.054) and significantly associated with AF detection (adjusted OR: 3.59, 95% CI: 1.07–12.06, p = 0.038). Conclusions: Our data suggest that LVDD with elevated LVFP is borderline associated with ESUS and significantly associated with AF detection on follow-up cardiac monitoring. Therefore, the presence of LVDD with an increased probability of elevated LVFP may help identify a subset of stroke patients more likely to have ESUS, potentially due to atrial cardiopathy with underlying occult AF. Further studies are needed to confirm our findings and to evaluate the safety and efficacy of anticoagulation in patients with ESUS and LVDD with elevated LVFP.

Background: Neuropathic pain (NeP) characterized by neuroplasticity and neuroinflammatory change is a common complication associated with spinal metastasis. However, there are no reliable candidates for diagnosis and treatment. Recently, cancer research has incorporated molecules into the treatment of patients with NeP, therefore, it is necessary to find key molecules of NeP to provide new targets for diagnosis and treatment.Methods: We analyzed RNA-seq data around the expression of ENPP6 based on bioinformatic methods, including differentially expressed genes (DEGs), Gene Ontology (GO), protein-protein interaction (PPI) network, Kyoto Encyclopedia of Genes and Genomes (KEGG) and GSEA analyses, receiver operating characteristic (ROC) curve, immune cell infiltration and mutation analysis.Results: We divided with pain samples into the High and Low ENPP6 expression groups. A total of 231 DEGs were identified. GO and KEGG analysis showed that DEGs were mainly enriched in Inflammation and cancer associated pathways. GSEA analysis showed that DEGs was significantly enriched in ARF3 and P38/MK2, RHO and RAS, and BRAFT and AKT1/E17K pathway. Pearson’s correlation analysis showed that the expression of ENPP6 was significantly correlated with autophagy phenotype and immunophenotype. Immune infiltrating analysis showed that activated NK cells were significantly highly expressed in Low group. ROC analysis of ENPP6 suggested that the area under the ROC curve was 0.925. Mutation sites analysis showed that most of the mutations in ENPP4-7 were phosphorylation sites.Conclusion: This study provides novel insights into molecular mechanisms underlying NeP, and identifying ENPP6 may serve as potentially diagnostic biomarkers and/or therapeutic targets for NeP.