Open Medicine最新文献

Objectives: Accurate diagnosis of acute cholecystitis (AC) is critical because early laparoscopic cholecystectomy significantly reduces complications and mortality. This study evaluates the predictive value of inflammatory indices and hematological markers in diagnosing AC.

Methods: A retrospective review was performed on early laparoscopic cholecystectomy cases at the Gaziosmanpaşa Training and Research Hospital in Istanbul between August 2013 and August 2023. Patient demographics, preoperative laboratory values, inflammatory indices - including neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) - were evaluated, along with hospital length of stay and histopathological outcomes.

Results: Among 249 patients, 34 (13.6%) were diagnosed with AC, comprising 76 males (30.5%) and 173 females (69.5%), with a mean age of 48.9 ± 14.6 years. The median hospital length of stay was 3 days (range: 1-21). Significant elevations in both the SIRI and neutrophil count were observed in AC cases compared to controls (P < 0.001). ROC (receiver operating characteristic) curve analysis demonstrated comparable diagnostic performance for the SIRI (AUC = 0.746; 95% CI: 0.658-0.835; optimal cutoff: 1.98) and neutrophil count (AUC = 0.746; 95% CI: 0.658-0.835; optimal cutoff: 7.1 × 10³/μL) in predicting AC.

Conclusions: The SIRI and neutrophil count are reliable markers that can improve the diagnostic accuracy and guide early management of AC.

Background: Postoperative cognitive dysfunction (POCD) is driven in part by microglial activation and the resulting neuroinflammatory response. Emerging evidence suggests that microRNAs regulate key inflammatory pathways in the central nervous system. In this study, we examined the role of the mmu‑miR‑125a/TRAF6 signaling axis in microglial activation under inflammatory conditions induced by lipopolysaccharide (LPS) and surgical trauma and evaluated whether dexmedetomidine (DEX) modulates this pathway to alleviate POCD.

Methods: Murine microglial cells were treated with LPS to induce activation. Expression levels of mmu‑miR‑125a and TRAF6 were quantified by qRT‑PCR and Western blotting. Bioinformatic prediction of miRNA binding sites was performed, and a luciferase reporter assay was used to confirm direct targeting of TRAF6 by mmu‑miR‑125a. Adult mice underwent standardized surgical trauma to induce POCD. Brain tissues were analyzed for microglial activation markers, cytokine levels, and expression of mmu‑miR‑125a and TRAF6. DEX was administered in both in vitro and in vivo models. The effects on cytokine release, microglial activation, and the mmu‑miR‑125a/TRAF6 axis were assessed.

Results: Our findings revealed significant alterations in the expression levels of TRAF6 and mmu-miR-125a during LPS-induced microglial activation. Through bioinformatics analysis and experimental validation, we identified TRAF6 as a direct target of mmu-miR-125a. The mmu-miR-125a/TRAF6 axis was found to be crucial for regulating microglial activation both in vitro, using an LPS-induced model, and in vivo, using a surgical trauma-induced POCD model. Moreover, we demonstrated that DEX, an alpha-2 adrenergic receptor agonist, effectively modulated the inflammatory cytokine release by targeting the mmu-miR-125a/TRAF6 axis in both models. The administration of DEX significantly suppressed microglial activation and TRAF6 expression, effects that were reversed by the inhibition of mmu-miR-125a.

Conclusion: Our study provides new insights into the molecular mechanisms underlying microglial activation and highlights the therapeutic potential of targeting the mmu-miR-125a/TRAF6 axis to alleviate neuroinflammation by the administration of DEX in POCD.

Background: Heart failure remains a major public health issue, and there are still no reliable biomarkers for left ventricular ejection fraction (LVEF).

Objective: To screen for differential metabolites in the blood of HFpEF, HFmrEF, and HFrEF patients based on metabolomics analysis of their blood samples.

Methods: Total 44 patients in HFpEF group, 30 patients in HFmrEF group, and 36 patients in HFrEF group were selected. The blood metabolites were analyzed by liquid chromatography high-resolution mass spectrometry and classified by principal component analysis, and then potential biomarker were screened. Partial least squares discriminant analysis was used to model and investigate the predictive ability of biomarkers for LVEF.

Results: Blood metabolite profiles of HFpEF, HFmrEF, and HFrEF groups could be well distinguished, and seven potential biomarkers were identified, such as phosphatidylcholine, phosphatidylinositol, lysophosphatidylcholine, lysophosphatidylcholine, ceramide, sphingosine, and sphingomyelin. Four metabolic pathways, such as glycerol phospholipid metabolic pathway, linoleic acid metabolic pathway, purine pyrimidine metabolism pathway, and linolenic acid metabolism pathway were identified, among which glycerol phospholipid metabolism pathway was the most significant.

Conclusion: The changes in glycerol phospholipid metabolism pathway may help identify HFpEF, HFmrEF, and HFrEF.

Introduction: Cardiac hemangiomas are slow-growing benign tumours of the heart. Patients may be asymptomatic or present a multitude of signs or symptoms.

Methods: We report herein the case of a 72-year-old woman with a giant right atrial mass. The patient suffers from abdominal swelling related to ascites. The histological examination of the tranjugular biopsy suspected an atrial myxoma.

Results: The patient was scheduled for surgical excision of the cardiac tumour. Radical resection of a 13 cm mass was performed. The histological diagnosis revealed cardiac hemangioma.

Conclusion: Cardiac hemangiomas can rarely grow larger than 5 cm, cause few symptoms, and are easily confused with atrial myxomas. Hepatomegaly and ascites may be signs of cardiac hemangioma.

[This corrects the article DOI: 10.1515/med-2023-0823.].

Introduction: Gestational diabetes mellitus (GDM), the most common metabolic complication of pregnancy, is associated with a 50% increase in subsequent risk for type 2 diabetes. There is increasing interest in identifying biomarkers that may facilitate the stratification of subsequent type 2 diabetes risk among women with GDM. In this study, we considered the choline acetyltransferase (ChAT) gene. CHAT plays a critical role in acetylcholine synthesis and regulates insulin secretion from the pancreatic islet to maintain glucose homeostasis.

Methods: We screened for deleterious variants in the ChAT gene in 12 GDM patients and 10 ethnically matched controls from a South African cohort. We isolated DNA from the placental samples of these patients and performed DNA sequencing of the protein-coding region of the ChAT gene. Sequence alignments and variant annotations were done using UGENE software and Ensembl VEP.

Results: A novel heterozygous missense variant in exon 8 of the ChAT gene was identified. The plausible phenotypic impact of the variant ChAT (NM_020549.5):c.1213C>G (p.Leu405Val) can be explained by haploinsufficiency, changing protein activities, strong transcription activity, and epigenetic repression activities of the variant. Also, structurally, the variant is located 18bp in-frame to a stop-gained variant (p.Gly411Ter). The RegulomeDB DNase expression data clearly show the identified variant in a peak expression in the spleen and placenta. This observation corroborates that the ChAT gene may play an essential role in GDM.

Conclusion: Taken together, the metric scores for this variant show that it could affect the functions of the gene, but more functional studies are necessary to validate these effects. Consequently, this study sets the stage for the future screening of a larger cohort and functional validation of deleterious variants to underpin the ChAT gene and GDM association.

Background: Intra-abdominal hypertension (IAH)/abdominal compartment syndrome (ACS) is one of the rarer clinical entities in the pediatric population, carrying a high degree of morbidity and mortality. The focus of this review is on assessing pathophysiological changes of organ systems in pediatric patients with risk factors for the occurrence of IAH/ACS based on the evaluation of diagnostic modalities and therapeutic strategies.

Methodology: A comprehensive literature search of indexed databases was performed, aiming to identify, review, and evaluate published articles on IAH/ACS. The search was focused on studies examining pathophysiology, risk factors, diagnostic approaches, and management strategies.

Results: The main risk factors encompass diminished abdominal wall compliance, increased intraluminal and abdominal contents, and capillary leak/fluid resuscitation. Diagnostic tools include clinical and imaging findings, intra-abdominal pressure (IAP) monitoring, and parameters of tissue perfusion. Therapeutic strategies involve non-surgical and surgical management of IAH/ACS in pediatric patients.

Conclusion: Timely and continuous evaluation of IAP and parameters of tissue perfusion is crucial for the early diagnosis of IAH/ACS and implementing non-surgical procedures, reducing the need for surgical procedures. Future research should focus on the usefulness of advanced non-invasive monitoring technologies and the identification of predictors of increased IAP in the early implementation of personalized therapeutic strategies.

Objective: This study aimed to investigate the potential causal relationship between immune cell and the risk of ulcerative colitis (UC), and to explore whether serum metabolites may mediate this association, thereby suggesting potential biomarkers or therapeutic targets.

Methods: We conducted a Mendelian randomization (MR) analysis using summary statistics from genome-wide association studies to evaluate both the direct effects and potential mediating roles of 731 immune cells and 1,400 serum metabolites in relation to UC. Instrumental variables were rigorously selected based on genome-wide significance and linkage disequilibrium thresholds. The primary analytical method was inverse variance weighted, supplemented by MR-Egger regression and weighted median methods to ensure robustness. Cochran's Q test, MR-Egger intercept, and leave-one-out analysis were employed to evaluate heterogeneity and pleiotropy. Mediation MR analysis was conducted to examine potential metabolite-mediated pathways.

Results: We identified a statistically significant positive causal effect of CD39⁺ CD4⁺ T cell on UC risk (OR = 1.05, 95% CI = 1.03-1.08, beta_all = 0.05). Sensitivity analyses confirmed the robustness of this association, and reverse MR analysis indicated no causal effect of UC on CD39⁺ CD4⁺ T cell, suggesting a unidirectional relationship. Mediation analysis further revealed that succinyl carnitine (C4DC) partially mediated the effect of CD39⁺ CD4⁺ T cell on UC, with a mediation proportion of 3.3%.

Conclusion: Our findings suggest that CD39⁺ CD4⁺ T cell may increase the risk of UC, potentially by modulating the levels of succinyl carnitine (C4DC). These results indicate a potential immunometabolic pathway in UC pathogenesis and highlight CD39⁺ CD4⁺ T cell and C4DC as promising targets for further research. However, additional experimental validation is required to confirm these findings and assess their clinical relevance.

Atherosclerosis (AS) is initiated by the activation of the endothelial cells, which is followed by a series of events that trigger the narrowing of blood vessels and the activation of inflammation. This study aimed to investigate in vitro the roles and underlying mechanisms of curdione in AS. Human umbilical vein endothelial cells (HUVECs) were stimulated with oxidized low-density lipoprotein (ox-LDL) and then treated with curdione, after which the growth of the HUVECs and the related mechanisms were determined. HUVECs with ERBB4 overexpression were constructed to explore the role of ERBB4 in curdione-mediated AS. The interaction among ERBB4, methylation, and curdione was confirmed by chromatin immunoprecipitation (ChIP)-quantitative PCR (qPCR) and dual luciferase reporter gene assays. Both curdione and ERBB4 overexpression individually and significantly enhanced viability and proliferation while suppressing apoptosis of the ox-LDL-induced HUVECs, and the combination of curdione and ERBB4 overexpression had better effects. Compared with the ox-LDL-induced HUVECs, both curdione and ERBB4 overexpression individually decreased the levels of IL-6, IL-1β, and IL-8 (P < 0.05). They also upregulated Bax, caspase-3, E-cadherin, and F-actin while downregulating Bcl-2 and VEGF (P < 0.05). Additionally, the ERBB4 bound to the DNMT1 gene, and the curdione participated in AS via the ERBB4 gene. The study demonstrated that either curdione or ERBB4 overexpression individually may ameliorate AS development by inhibiting apoptosis, inflammation, and the EndMT of HUVECs. In addition, curdione may protect the vascular endothelial cells and AS by regulating the DNMT1-mediated ERBB4 promoter methylation.