European Journal of Medical Research最新文献

Objective: Idiopathic inflammatory myopathy (IIM) is a collection of autoimmune disorders marked by muscle inflammation, with heart failure (HF) being a common and deadly complication. Exploring the underlying mechanisms and diagnostic markers for HF in IIM has significant clinical value.

Methods: We identified shared differentially expressed genes (DEGs) between HF and IIM using transcriptome data from the Gene Expression Omnibus (GEO). DEGs underwent functional enrichment analysis via Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). Key genes were screened using two machine-learning algorithms and a protein-protein interaction network. Immune cell infiltration was estimated using the CIBERSORT algorithm, and its correlation with key genes was assessed. The key gene-related regulatory transcription factors (TFs) and miRNAs were predicted using miRNet, followed by validation through both online datasets and clinical samples.

Results: Seventy DEGs were shared by IIM and HF, primarily involved in immune and inflammatory responses. Key genes, including DDX60, CCL5, and IFIT3, exhibited strong diagnostic potential in both IIM and HF cohorts. Expression of IFIT3 and CCL5 was negatively associated with Tregs. In order to uncover the control of important genes, we also constructed TF-gene and miRNA-gene networks. Lastly, we confirmed that IIM with HF had higher levels of miR-100-5p expression than those without HF.

Conclusion: DDX60, CCL5, and IFIT3 are likely central to the development of HF in IIM. Additionally, serum levels of miR-100-5p may serve as a potential biomarker for detecting HF in IIM patients.

Aims: This study aimed to investigate the potential efficacy and safety of conduction system pacing (CSP) upgrades in patients indicated for elective replacement (ERI) with a left ventricular ejection fraction (LVEF) of less than 50% including those with heart failure with mildly reduced ejection fraction (HFmrEF).

Methods: This observational, retrospective cohort study included all patients with an LVEF < 50% who had a right ventricular pacing percentage of ≥ 40% prior to pulse generator replacement from January 2018 to October 2021. Cardiac performance and lead outcomes were compared across different LVEF groups based on whether they received CSP upgrades.

Results: A total of 60 patients were enrolled in this study, comprising 29 patients who successfully underwent CSP upgrades (29/32, 90.46%) and 31 patients who declined the upgrades. Comparable improvements in LVEF (9.00 ± 5.90% vs. 5.90 ± 3.72%, P = 0.325) and LVEDD (2.80 ± 1.95 mm vs. 3.10 ± 2.60 mm, P = 0.835) were noted in patients with HFmrEF. However, the final LVEF (53.50 ± 6.06 vs. 40.10 ± 10.20, P = 0.031) and LVEDD (48.60 ± 4.79 vs. 55.67 ± 9.80, P = 0.040) were more favorable in patients with HFmrEF compared to those with heart failure with reduced ejection fraction (HFrEF). In patients who declined CSP upgrades, NYHA grade (2.92 ± 0.79 vs. 2.75 ± 0.45, P = 0.010) and LVEF (29.50 ± 8.19% vs. 32.92 ± 5.25%, P = 0.018) decreased in patients with HFrEF, while comparable reductions in LVEF (45.84 ± 3.00% vs. 39.89 ± 10.83%, P = 0.001) and LVEDD (55.86 ± 9.62 mm vs. 50.11 ± 6.26 mm, P = 0.044) were observed in patients with HFmrEF. No complications, including thrombosis, infection, lead dislodgement, perforation, or stroke, were reported. The pacing threshold (1.25 ± 0.45 V vs. 1.57 ± 0.55 V, P = 0.129) did not differ significantly between patients with CSP upgrades and those without, following a follow-up period of 40.57 ± 8.21 months.

Conclusion: CSP upgrade during pulse generator replacement for battery depletion was associated with improved cardiac performances in patients with LVEF less than 50%. The final cardiac performance in patients with HFmrEF is more favorable. Larger-scale randomized controlled studies are therefore necessary to validate these findings, confirm the efficacy of CSP upgrade, and establish its optimal timing.

Background: On a global scale, coronary artery disease (CAD) continues to be one of the leading causes of morbidity and death. Glycosylation, a vital post-translational modification, has been linked to a range of cardiovascular conditions, including CAD. This study aims to systematically identify and validate glycosylation-based prognostic biomarkers for CAD, with the ultimate goal of developing a novel clinical diagnostic tool.

Methods: We sourced and pre-processed CAD data sets (GSE20680, GSE20681, GSE42148) from the Gene Expression Omnibus (GEO) database, which comprised 199 CAD samples and 162 control samples post batch effect removal. DE analysis was executed using the R software to pinpoint glycosylation-related differentially expressed genes (GRDEGs), whose functional enrichment analysis was conducted subsequently. Risk scores were calculated using a diagnostic model that was built employing logistic regression (LR), support vector machine (SVM) algorithms, and least absolute shrinkage and selection operator (LASSO) regression analysis. The model further underwent validation employing receiver operating characteristic (ROC) curves, calibration plots, as well as decision curve analysis (DCA). The infiltrated abundance of the immune cells between the high-risk group (HRG) and low-risk group (LRG) was then analyzed by ssGSEA to explore the effect of the GRDEG-based prognostic signatures on the immune response. Furthermore, the interaction networks were constructed to explore the potential regulatory mechanisms and therapy approaches based on the GRDEGs. Finally, the levels of the GRDEG-based prognostic signatures in CAD samples were detected using qRT-PCR and western blotting.

Results: Thirty-nine GRDEGs were significantly and differently expressed between the CAD and control groups, which predominantly participate in protein glycosylation and N-Glycan biosynthesis pathways. Among these genes, seven GRDEGs were identified as the prognostic risk signatures, including F5, MGAT4A, HSPG2, ARSB, TUBB3, ST6GAL1, and CAMLG. Based on these genes, the CAD samples were separated into HRG and LRG, and the ICI between HRG and LRG were shown to be significantly different. The constructed interaction networks further suggested that the seven GRDEGs were regulated by several microRNAs (miRNAs), transcription factors (TFs), and RNA-binding proteins (RBPs), and they were the target genes of some chemical drugs. Finally, the outcomes of qRT-PCR and western blotting demonstrated that there were significant variations in expressing these seven key genes in CAD.

Conclusions: This study establishes the critical role of GRDEGs in CAD pathogenesis and presents a robust diagnostic model with potential clinical utility. Furthermore, our findings reveal novel molecular targets that may inform future therapeutic strategies for CAD.

Background: Effective pain management following hip arthroplasty is critical for patient recovery. As a key component of multimodal analgesia strategies, nerve blocks are widely utilized for postoperative analgesia. However, the comparative efficacy of different nerve block techniques remains unclear. This study employs a Bayesian network meta-analysis (NMA) to compare analgesic outcomes among six commonly used nerve block techniques after hip arthroplasty.

Methods: Randomized controlled trials (RCTs) comparing postoperative pain outcomes among six nerve block techniques-supra-inguinal fascia iliaca block (FIB), erector spinae plane block (ESPB), quadratus lumborum block (QLB), pericapsular nerve group block (PENG), lumbar plexus block (LPB), and circum-psoas block (CPB)-after hip arthroplasty were systematically searched in PubMed, Embase, Web of Science, and the Cochrane Library from inception to October 15, 2024. 15 RCTs involving 1,068 patients were included. Methodological quality and evidence certainty were assessed using Cochrane RoB 2.0 and GRADE framework. A Bayesian NMA with random/fixed-effects models integrated direct and indirect evidence. Interventions were ranked using the surface under the cumulative ranking curve (SUCRA). Outcomes included static/dynamic pain scores at 12 and 24 h, 24-h intravenous morphine consumption, and postoperative adverse effects (nausea, vomiting, and dizziness).Data were analyzed using R 4.4.1 and Stata 15.

Results: 15 RCTs (n = 1068) comparing six nerve block techniques were included. The NMA showed no statistically significant differences in static or dynamic pain scores at 12 or 24 h. For 24-h morphine consumption, CPB was associated with significantly lower use compared to QLB and FIB. Statistically significant differences were found for postoperative adverse effects. SUCRA rankings consistently indicated CPB had the highest probability of being among the most effective options across outcomes, followed by PENG. The overall certainty of evidence was moderate.

Conclusions: This NMA found no significant differences in analgesia among six nerve blocks after hip arthroplasty, but SUCRA rankings suggest CPB may be optimal for analgesia, morphine-sparing and postoperative adverse effects, while PENG may serve as an alternative in selected clinical contexts.

Registration: PROSPERO (CRD420251101790).

Background: The triglyceride glucose (TyG) index, a surrogate marker of insulin resistance, has been linked to cardiovascular risk. However, its prognostic role in critically ill patients with atherosclerotic cardiovascular disease (ASCVD) remains unclear.

Methods: In this retrospective cohort study using the MIMIC-IV database, we identified 2,493 ASCVD patients and stratified them into TyG tertiles upon Intensive Care Unit (ICU) admission. Primary outcomes were 30-, 90-, and 365-day mortality. Secondary outcomes included the use and timing of mechanical ventilation (MV) and vasopressors. Cox regression, restricted cubic spline, and Fine-Gray competing risk models were applied. Propensity score matching (PSM) was performed as a sensitivity analysis. Subgroup analyses were conducted by age, sex, race, hypertension, diabetes, and statin use. Mediation analysis using white blood cell (WBC) count explored systemic inflammation.

Results: Higher TyG tertiles were consistently associated with increased mortality: 30-day (HR 1.85, 95% CI 1.46-2.36, P < 0.001), 90-day (HR 1.73, 95% CI 1.39-2.15, P < 0.001), and 365-day (HR 1.66, 95% CI 1.37-2.03, P < 0.001). These associations remained robust in propensity score-matched (PSM) analyses. Elevated TyG was also linked to greater need for MV (OR 1.93, 95% CI 1.66-2.24, P < 0.001) and vasopressor support (OR 1.58, 95% CI 1.35-1.86, P < 0.001) within the first 24 h, and to earlier initiation of these interventions in competing risk models (MV): sHR (subdistribution hazard ratio) 1.46, 95% CI 1.35-1.57, P < 0.001; vasopressor use: sHR 1.41, 95% CI 1.30-1.53, P < 0.001. WBC count partially mediated the TyG-mortality association, accounting for 22.18% of the total effect (P < 0.001) for 30-day mortality. In exploratory subgroup analyses, the association between TyG and mortality appeared more pronounced in nondiabetic patients (30-day HR 1.58, 95% CI 1.35-1.84) than in diabetic patients (HR 1.13, 95% CI 0.94-1.36), although these findings should be interpreted cautiously.

Conclusion: In critically ill patients with ASCVD, higher TyG index was associated with adverse outcomes, including increased mortality and earlier initiation of organ-supportive interventions. These findings suggest that TyG could serve as a practical biomarker for early risk stratification in this high-risk population, though prospective studies are warranted to confirm its clinical utility.

Background: The identification of reliable biomarkers for clinical diagnosis and prognostic evaluation of severe pneumonia remains challenging. Long non-coding RNA (lncRNA) TINCR, along with its genetic variant rs2288947, has been suggested to play a role in the pathophysiology of severe pneumonia. This study aimed to examine the relationship between the rs2288947 polymorphism and the risk of developing severe pneumonia, the degree of inflammatory response, and 28-day outcomes in pediatric patients.

Methods: A total of 355 children diagnosed with severe pneumonia and 326 healthy controls were included. Plasma lncRNA TINCR expression was measured via qRT-PCR, and rs2288947 genotyping was performed using the TaqMan assay. 28-day survival based on Kaplan-Meier analysis were assessed. Multivariate Cox regression was employed to determine independent prognostic factors.

Results: Expression of lncRNA TINCR was significantly reduced in the severe pneumonia group compared to controls. At the rs2288947 locus, the presence of the A allele was correlated with downregulated expression of the lncRNA TINCR. Carriers of the GA or AA genotypes consistently demonstrated decreased lncRNA TINCR expression levels. The AA genotype and the A allele of rs2288947 were associated with an elevated risk of severe pneumonia. Patients carrying the GA + AA genotypes showed higher levels of inflammatory markers (WBC, CRP, PCT, neutrophils) and a lower 28-day survival rate. The rs2288947 polymorphism was identified as an independent prognostic factor.

Conclusions: The rs2288947 variant may represent a useful biomarker for evaluating susceptibility and predicting prognosis in pediatric severe pneumonia.

Background: Timely administration of antibiotics is critical in the management of infectious diseases, particularly in preventing progression to sepsis. Despite the urgency, the appropriate timing of antibiotic treatment, especially in non-septic infections, remains unclear. This study aimed to assess the association between antibiotic timing and progression to sepsis among patients admitted to the Emergency Department (ED) for suspected infection.

Methods: A retrospective cohort study utilized data from three tertiary-care hospital EDs between January 2021 and June 2023. Adult patients hospitalized for clinical infection were included. The primary outcome was sepsis development, while secondary outcomes included hospital mortality, Intensive Care Unit (ICU) admission, ICU length of stay (LOS), and hospital LOS. The main exposure was the duration from ED arrival to initial antibiotic administration. Multivariable logistic and negative binomial regression were employed to adjust for confounders and assess associations.

Results: The study included 1279 infected adult patients, with 20.5% developing sepsis and 10.3% admitted to the ICU, resulting in 3.8% in-hospital deaths. The median time from ED arrival to initial antibiotic administration was 123 min (interquartile range(IQR), 79-241 min). Although per-hour delays in antibiotic administration showed association with sepsis development (Adjusted Odds Ratio(aOR) (95% CI) 1.071(1.044-1.099); P < 0.001), the primary threshold analysis demonstrated that significant associations with sepsis (aOR (95% CI), 3.468 (2.131-5.623); P < 0.001), in-hospital mortality (aOR 2.487, 95% CI 1.083-5.440; P = 0.026), adverse clinical outcomes, and prolonged LOS emerged only when delays exceeded 12 h. These findings were also confirmed by sensitivity analyses.

Conclusions: These hypothesis-generating findings suggest that, in non-severe infections, delays within 12 h might not be associated with significantly increased risks, potentially allowing time for diagnostic clarification without apparent harm. However, due to the observational nature of the study and potential biases, prospective studies are required to confirm these associations.

Introduction: Gallstone disease (GSD) is a common hepatobiliary disorder influenced by bile composition, biliary drainage, and gallbladder motility. Emerging evidence suggests that oral microbiota may contribute to GSD development, but its role remains unclear. This study explores salivary microbiome alterations in GSD patients and their potential clinical relevance.

Methods: This study enrolled 58 GSD patients and 10 age-matched healthy controls. Salivary microbiome profiles were characterized using high-resolution 16S rRNA amplicon sequencing. All participants underwent comprehensive clinical evaluations including physical examinations, oral health assessments, anthropometric measurements, and fasting venous blood sampling for serum biochemical analysis. A multi-dimensional approach was applied to investigate host-microbiome interactions and their potential role in GSD pathogenesis.

Results: Comparative analysis revealed significant microbial divergence between GSD patients and healthy controls, characterized by increased α-diversity indices and distinct β-diversity clustering. The linear discriminant analysis effect size (LEfSe) analysis identified 65 differentially abundant taxonomic features across multiple phylogenetic levels, including 7 phyla, 9 classes, 11 orders, 16 families, and 22 genera, representing 550 operational taxonomic units (OTUs). Notably, Veillonella, Neisseria, Prevotella, and Lachnoanaerobaculum were markedly enriched in the GSD cohort. The developed eXtreme Gradient Boosting (XGBoost) diagnostic model demonstrated exceptional discriminatory capacity, achieving a mean AUC of 0.994 under rigorous fivefold cross-validation. Redundancy analysis (RDA) and Spearman correlation analysis showed strong associations between microbial community structure and key biochemical markers, including chenodeoxycholic acid (CDCA) and alkaline phosphatase (ALP). Functional prediction using PICRUSt2 indicated substantial metabolic pathway alterations in GSD patients, particularly enhanced activity in energy production, amino acid metabolism, and secondary metabolite biosynthesis.

Conclusions: Salivary microbiome dysbiosis in GSD patients demonstrated significant associations with disrupted bile acid homeostasis, suggesting a potential role of the oral microbiota in modulating lithogenic processes. The markedly altered microbial signatures may contribute to GSD pathogenesis, while the XGBoost-based diagnostic model shows considerable promise as a noninvasive tool for GSD detection.

Purpose: To characterize spectrum-dependent changes in Scheimpflug tomographic parameters across normal, keratoconus suspect, and eyes with keratoconus classified using the modified Rabinowitz-McDonnell index.

Methods: This retrospective comparative study included 115 eyes of 115 patients evaluated at a tertiary ophthalmology clinic. Based on the modified Rabinowitz-McDonnell index, eyes were categorized into control (n = 37), keratoconus suspect (n = 51), and keratoconus (n = 27) groups. All eyes underwent Scheimpflug tomography. Anterior and posterior keratometry values, corneal thickness parameters, corneal volume, anterior chamber depth, and pupil diameter were analyzed.

Results: Anterior and posterior corneal curvature parameters increased progressively from control group to keratoconus suspect group and were highest in eyes with keratoconus (all p < 0.001). While anterior keratometric parameters and posterior corneal curvature differed significantly between control and keratoconus suspect groups, pachymetric measurements remained comparable, with significant thinning observed only in the keratoconus group (all p < 0.001). Corneal volume was higher in keratoconus suspect group compared with both control and keratoconus groups (p = 0.001). Anterior chamber depth was greater in keratoconus group, while pupil diameter was smaller in keratoconus suspect group (both p < 0.01).

Conclusion: When keratoconus is classified using central keratometry, Scheimpflug tomography demonstrates a clear, stage-dependent pattern of corneal change. Curvature-related alterations precede measurable thinning, highlighting that curvature-based classification remains clinically relevant and that tomographic parameters can enhance disease characterization across the keratoconus spectrum.