European Journal of Medical Research最新文献

Background: Coronary heart disease (CHD) remains a leading global cause of morbidity and mortality. Dyslipidemia-particularly elevated non-high-density lipoprotein cholesterol (non-HDL-C) and reduced high-density lipoprotein cholesterol (HDL-C)-is a key risk factor for CHD. The ratio of non-HDL-C to HDL-C (NHHR) has been proposed as an integrative marker of lipid-related risk. We separately examined the cross-sectional association of NHHR with CHD status and its prospective association with long-term mortality in a nationally representative U.S.

Cohort:

Methods: We analyzed data from adults (aged ≥ 18 years) in NHANES 2005-2016. NHHR was calculated as non-HDL-C divided by HDL-C. Cross-sectional associations between NHHR and self-reported CHD were assessed using multivariable logistic regression. Prospective associations of baseline NHHR with all-cause and cardiovascular mortality were examined using Cox proportional hazards models. Restricted cubic splines (3 knots) were used to explore potential nonlinear relationships.

Results: Among ~ 20,000 adults, higher NHHR was paradoxically associated with lower odds of self-reported CHD. In fully adjusted models, participants in the highest NHHR quartile had an odds ratio of 0.39 (95% CI, 0.31-0.50; p < 0.0001) compared to the lowest quartile. In longitudinal analyses over a median follow-up of 7-10 years, higher NHHR was associated with lower hazard of all-cause and cardiovascular mortality. Spline analyses suggested a U-shaped relationship, with nadirs at NHHR ≈3.4 for all-cause and ≈3.3 for cardiovascular mortality (P for nonlinearity < 0.001).

Conclusions: In this large NHANES-based observational study, NHHR was cross-sectionally associated with lower CHD prevalence and longitudinally associated with reduced mortality. While similar patterns have been reported in prior NHANES studies, our analysis contributes additional insight by jointly modeling both CHD and mortality outcomes using nonlinear spline approaches and subgroup analyses. The paradoxical inverse association with CHD may reflect residual confounding or reverse causality. These findings remain exploratory and require cautious interpretation and further validation.

Purpose: This study aimed to investigate the distribution of epicardial adipose tissue (EAT) and adipose metabolism in patients with obstructive sleep apnea (OSA) without comorbidities, such as cardiovascular disease and diabetes-an approach to eliminate confounding factors and explore the role of EAT in OSA-related visceral adipose disorders.

Methods: The clinical data of 180 patients were retrospectively collected from July 2017 to December 2023 at the Department of Otolaryngology-Head and Neck Surgery, Second Affiliated Hospital of Xi'an Jiaotong University. Patients were categorized into mild-moderate (apnea-hypopnea index, AHI < 30 events/hour) and severe OSA groups (AHI ≥ 30 events/hour) based on their polysomnography (PSG) results. Epicardial adipose tissue volume (EATV) and attenuation (EATA) were quantified using coronary computed tomography angiography and 3D-Slicer software, with adipose tissue defined by a Hounsfield unit threshold of -190 to -30 HU. The Chinese visceral adiposity index (CVAI) is a composite metric specific to the Chinese population that integrates age, body mass index, waist circumference, triglyceride, and high-density lipoprotein levels.

Results: Significant differences were observed in EATV, EATA, and CVAI between the mild-moderate and severe OSA groups (all p < 0.05). Elastic net regression, restricted cubic spline curves, and subgroup analysis using forest plots demonstrated that CVAI had the strongest correlation with the apnea-hypopnea index (AHI) and OSA severity among the visceral adipose parameters (all p < 0.05). After controlling for the effects of baseline data and visceral adipose tissue, multiple linear regression analysis revealed that OSA severity still affected the EATV and EATA (all p < 0.05).

Conclusions: OSA progression without cardiovascular disease and diabetes may promote an increase in EATV, especially in the atrial region. In addition, the change in epicardial adipose tissue appears to be independent of visceral adipose tissue. This underscores EAT as a distinct fat depot and highlights its potential role in early cardiovascular risk assessment for OSA patients, offering perspectives for future research into mechanistic pathways and clinical interventions.

Objectives: To investigate and analyze the factors affecting postoperative urinary retention (POUR) after pelvic floor reconstruction, and to construct and validate a risk prediction model.

Methods: This retrospective cohort study included 258 pelvic floor reconstruction patients (2023-2024) from a Southwest China tertiary hospital. Patients were classified into POUR and non-POUR groups and split 7:3 into training and internal validation cohorts. Predictors were identified through univariate analysis and multivariate logistic regression analysis to construct a Nomogram model. Receiver Operating Characteristic (ROC) curves, calibration curves, and the Hosmer-Lemeshow test evaluated the model's differentiation, calibration, goodness-of-fit, and predictive performance.

Results: Independent POUR risk factors were: urinary retention history (OR = 10.008, 95% CI 1.368-73.195, P = 0.023), heart disease (OR = 14.416, 95% CI 2.872-72.376, P = 0.001), number of vaginal deliveries (OR = 1.569, 95% CI 1.076-2.289, P = 0.019), and maximal urinary flow rate (OR = 0.845, 95% CI 0.76-0.94, P = 0.002). The AUC values of the training cohort and internal validation cohort were 0.812 (95% CI 0.726-0.899) and 0.822 (95% CI 0.703-0.941), respectively. Calibration curves indicated good agreement between predicted and observed values, and the Hosmer-Lemeshow test demonstrated high predictive accuracy (P > 0.05).

Conclusions: The nomogram model effectively predicts POUR risk, aiding early perioperative identification of high-risk patients.

Background: To assess the impact of oil overlay during maturation of immature oocytes in vitro in our optimized liquid culture system.

Methods: We conducted comparative analyses of pH, osmolality, and the levels of melatonin, FSH, E2, and hCG in the culture medium between oil-covered group (OC group) and non-oil-covered group (non-OC group). Furthermore, germinal vesicle (GV) oocytes were collected and matured into MII phase in our culture medium for 24 h. Subsequently, levels of ROS, SOD, MDA, and LDH were tested in OC group and non-OC group using either microplate assays or chemical fluorescence techniques. Finally, a total of 2432 immature oocytes obtained from controlled ovarian hyperstimulation (COH) cycles underwent in vitro maturation (IVM) in culture media with or without oil supplementation (1380 and 1052 oocytes, respectively), followed by insemination and embryo culture. The IVM prognostic indicators were assessed and compared between OC group and non-OC group.

Results: There were no statistically significant differences in pH and osmolality values between the OC group and the non-OC group. However, the concentrations of melatonin, FSH, E2, and hCG in non-OC group were significantly elevated in the non-OC group compared to the OC group. Regarding oxidative stress parameters, levels of ROS, MDA, and LDH in the culture medium of the non-OC group were lower than those in the OC group, while SOD levels were higher in the non-OC group. Furthermore, the clinical outcome assessments revealed significantly higher rates of maturation, cleavage, and blastocyst formation in the non-OC group compared to the OC group, with no discernible difference in fertilization rates between the two groups.

Conclusion: Omission of mineral oil overlay enhances hormone bioavailability, diminishes oxidative stress, and significantly improves oocyte maturation and blastocyst formation rates in IVM culture.

Background: Periodontal ligament stem cells (PDLSCs) are essential for periodontal tissue regeneration, but their osteogenic differentiation is significantly impaired in the inflammatory microenvironment of periodontitis. This study aimed to investigate the regulatory role of the SENP6-SMAD5-SOX2 axis in PDLSC osteogenesis.

Methods: Transcriptomic analysis of public datasets was used to identify key regulators. In vitro functional experiments, including siRNA-mediated knockdown, co-immunoprecipitation, and luciferase assays, were performed on PDLSCs isolated from healthy donors. The expression of SOX2 and early osteogenic markers (ALP and RUNX2) was assessed at day 7 of osteogenic induction. In vivo, the SENP6 inhibitor NSC632839 was evaluated in an LPS-induced mouse calvarial osteolysis model via micro-CT and H&E histological assessment.

Results: In periodontitis tissues, SMAD5 protein was downregulated despite mRNA upregulation. In healthy PDLSCs, SENP6 knockdown stabilized SMAD5 protein and significantly upregulated the expression of SOX2 and early osteogenic markers ALP and RUNX2. Mechanistically, SMAD5 directly activated SOX2 transcription. In the mouse calvarial model, NSC632839 treatment effectively promoted bone formation and increased the bone volume fraction (BV/TV) through SOX2 upregulation, while the SMAD5 inhibitor CDD1653 exacerbated bone loss.

Conclusions: The SENP6-SMAD5-SOX2 axis is a critical regulator of early PDLSC osteogenic commitment. Pharmacological inhibition of SENP6 offers a promising therapeutic strategy for restoring bone regeneration in inflammatory environments.

Accumulating evidence indicates that glutaminase (GLS) serves as a crucial player in cell proliferation and survival of cancers. Nonetheless, the roles and mechanisms of GLS in esophageal squamous cell carcinoma (ESCC) have not been elucidated. Herein, we found that GLS was over-expressed in glutamine-dependent ESCC cells and ESCC tissues. Patients with high GLS expression had a worse prognosis than those with low GLS expression. In ESCC cells, GLS knockdown inhibited the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of ESCC cells and promoted apoptosis. RNA-Seq analysis combined with immunoblotting showed that GLS knockdown reduced the TGF-β, p-Smad2/3, p-p38MAPK, p-ERK1/2, and p-MEK1/2 proteins, increased ROS and glutamine levels in both KYSE30 and KYSE150 cells. Overall, our study showed that GLS promoted the malignant progression via the TGF-β signaling pathway, suggesting that GLS can be a potential therapeutic target and diagnostic biomarker for ESCC.

Background: MASLD is the most common chronic liver disease and the leading cause of liver-related morbidity and mortality globally. While probiotic supplementations show promise as adjunctive therapy, existing trials are limited by the quality of evidence, small sample sizes, and methodological inconsistencies, highlighting the need for well-designed studies, particularly on multi-strain synbiotics. Therefore, we conducted this trial to evaluate the effects of multi-strain synbiotic combined with lifestyle modifications, including an individualized diet and physical activity program, on patients with MASLD.

Methods: In this randomized, double-blinded, placebo-controlled trial, 80 MASLD patients were enrolled and underwent lifestyle modifications. Participants were randomized in a 1:1 ratio to receive either synbiotic capsules (500 mg each, 10⁹ CFU per capsule) containing two strains of Bifidobacteria, two strains of Lacticaseibacillus, two strains of Lactobacillus, and one strain of Streptococcus, as well as Fructooligosaccharides as prebiotic, or placebo (one capsule every 12 h) for 12 weeks. All patients were evaluated both at the beginning and the end of the trial in terms of anthropometric parameters (weight, BMI, and WC), hematological parameters (Hb and Plt), coagulation status (PT and INR), lipid profile (TG, TC, HDL-C, and LDL-C), FBS, liver function (ALT and AST), and liver inflammatory biomarkers (TNF-α and IL-6).

Results: No significant changes were observed in anthropometric measures either within or between groups during the study period. Moreover, analysis of venous blood samples at the end of the trial showed significant improvements in some measures of lipid profile (TC and LDL-C), FBS, liver function (ALT and AST), and liver inflammatory biomarkers (TNF-α and IL-6) in the synbiotics-receiving group compared to both the beginning of the trial and the placebo-receiving group. However, no significant changes were observed in hematological parameters (Hb and Plt), coagulation status (PT and INR), and lipid profile (TG and HDL-C) compared to the beginning of the trial and the placebo-receiving group. Supplements were tolerated well, with no complications or allergic reactions reported.

Conclusions: Supplementation with multi-strain synbiotics, in combination with lifestyle modifications, could serve as a promising adjunctive therapy to control disease progression in patients with MASLD.

Background: Sepsis constitutes a critical clinical condition characterized by organ failure and systemic inflammation, especially affecting children. Lipid metabolism and endoplasmic reticulum stress are involved in various diseases, yet their roles in pediatric sepsis remain unclear. This study sought to discover and validate biomarkers associated with lipid metabolism and endoplasmic reticulum stress in pediatric sepsis.

Methods: Differentially expressed genes were identified from the Gene Expression Omnibus (GEO) database. Lipid metabolism-related genes (LRGs) and endoplasmic reticulum stress-related genes (ERGs) were sourced from literature. After weighted gene co-expression network analysis and intersections, candidate genes were screened by machine learning and validated. A nomogram was built, followed by various bioinformatics analyses and quantitative reverse transcriptase PCR (qRT-PCR) confirmation.

Results: There were 12 candidate genes, and 4 of them (ACER3, DGAT2, GBA, and TSPO) were screened as biomarkers. A nomogram integrating these four biomarkers showed excellent predictive ability. Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA) revealed their involvement in pediatric sepsis-related pathways. They correlated positively with stimulated dendritic cells and negatively with stimulated B cells. The molecular regulatory network included multiple RNAs and transcription factors. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) bound strongly to the biomarkers. qRT-PCR confirmed their high expression in pediatric sepsis patients' blood (all P < 0.05).

Conclusions: A total of 4 biomarkers (ACER3, DGAT2, GBA, and TSPO) related to lipid metabolism and endoplasmic reticulum stress in pediatric sepsis were identified. These biomarkers offered fresh insights into the mechanisms and therapeutic approaches of pediatric sepsis.

Background: The emerging concept of cardiovascular-kidney-metabolic syndrome (CKM) highlights the pathophysiological interconnection between cardiorenal and metabolic disorders. This study investigates the longitudinal association between the cardiometabolic index (CMI) and CKM stage progression.

Methods and results: This study utilized data from the China Health and Retirement Longitudinal Study. The baseline CMI was computed utilizing the triglycerides-to-high-density lipoprotein cholesterol ratio multiplied by the waist-to-height ratio. CKM is defined and categorized into five stages (0-4) based on metabolic, cardiovascular, and renal disorders. We evaluated the impact of CMI on the CKM stage progression from Wave 1(2011) to Wave 3(2015). Multivariable logistic regression and restricted cubic spline (RCS) models were constructed to illustrate the relationship between CMI and CKM stage progression. A total of 4080 patients were included. The rate of CKM progression to advanced stages significantly increased with higher CMI quartiles. When entered into the multivariable logistic regressions as a continuous variable, elevated CMI was a remarkable predictor for progression to CKM stages 2-4 among participants at baseline CKM stages 0-1 [OR(95%CI) 1.66 (1.32-2.11)], progression to CKM stages 3-4 among those at baseline CKM stages 0-2 [OR(95%CI) 1.14 (1.03-1.26)], and progression to CKM stage 4 among those at baseline CKM stages 0-3 [OR(95%CI) 1.13 (1.00-1.28)], after adjustment for potential confounders. This association persisted when CMI was modeled as a categorical variable. RCS analysis demonstrated significant positive associations between elevated CMI levels and an increased risk of progression to advanced CKM stages (all P < 0.05).

Conclusion: Elevated CMI is significantly associated with CKM stage progression over time. CMI could act as a simple, useful tool for the risk assessment of CKM.

Background: The pulmonary microbiome is increasingly recognized as a key determinant of pneumonia severity, yet its clinical implications remain incompletely understood. Disruption of microbial ecology, or dysbiosis, may impair host immune responses and exacerbate disease progression. This study aimed to characterize microbiome alterations associated with severe pneumonia and their correlation with host inflammatory and coagulative parameters.

Methods: In this multicenter, prospective observational cohort study conducted across nine hospitals in Shanghai (2021-2025), bronchoalveolar lavage fluid (BALF) samples from 306 patients with clinically diagnosed pulmonary infections were analyzed using metagenomic next-generation sequencing (mNGS). Patients were stratified into severe (n = 196) and non-severe (n = 110) groups using WHO-derived severe pneumonia criteria at the time of bronchoalveolar lavage (BAL). Microbial taxonomic profiles, diversity indices, co-occurrence networks, and correlations with clinical markers were comprehensively assessed using standard bioinformatic and statistical approaches.

Results: Severe pneumonia was associated with marked microbial dysbiosis, including reorganization of co-occurrence network topology with centrality shifting away from commensals toward opportunistic taxa in severe disease, characterized by reduced α-diversity, altered β-diversity, and enrichment of opportunistic Gram-negative pathogens including Acinetobacter and Klebsiella. In contrast, commensals such as Rothia and Prevotella were depleted. Co-occurrence network analysis revealed fragmentation of microbial interactions in severe cases, with centrality shifting from commensals to opportunists like Corynebacterium striatum. Shannon diversity negatively correlated with SOFA scores, and specific taxa positively associated with systemic inflammation (CRP, PCT) and coagulation abnormalities. Nearly all samples demonstrated polymicrobial infection, with distinct microbial patterns observed across monomicrobial and polymicrobial subgroups.

Conclusion: Our multicenter observational analysis suggests that severe pneumonia is associated with marked ecological disruption of the lower-airway microbiome, characterized by commensal loss, opportunist expansion, and fragmented interspecies networks, and with concurrent inflammatory and coagulative abnormalities. These hypothesis-generating findings warrant external validation in independent, multi-region cohorts and longitudinal sampling to test directionality and causality before informing clinical decision-making.