Biomolecules & biomedicine最新文献

Delays in intensive care unit (ICU) admissions are prevalent in overcrowded hospitals and can adversely affect patient outcomes. However, the extent of this impact, particularly beyond short-term mortality, remains unclear. We hypothesized that ICU admission delays exceeding 6 hours after consultation would independently increase 90-day mortality and prolong ICU length of stay. We conducted a retrospective analysis of data from 273 adult patients admitted to the ICU of a tertiary university hospital between January and December 2019. Patients were stratified into two groups: early admission (≤6 hours) and delayed admission (>6 hours). Multivariate Cox regression was employed to identify independent predictors of mortality. Delayed ICU admission was observed in 72.8% of patients. Although delayed admission was not independently associated with increased mortality in the multivariate analysis (HR: 0.88; 95% CI: 0.61-1.27), it was significantly correlated with prolonged ICU length of stay and higher 90-day mortality in the univariate analysis (p = 0.039), with no significant difference in vasopressor-free days (p = 0.809). In our assessment of independent mortality predictors, we found that patients with higher APACHE-II and Charlson scores experienced longer delays in ICU transfer. Additionally, respiratory and circulatory failure at admission were independently associated with increased mortality (HR: 2.17; 95% CI: 1.51-3.12). While early ICU admission did not independently predict mortality, it was linked to extended ICU stays, an increased treatment burden, and adverse long-term outcomes. These findings underscore the necessity of refining triage processes and evaluating baseline patient severity when interpreting the impact of ICU admission timing on outcomes.

Nicotine addiction poses a significant public health threat, particularly within the realm of emergency medicine, where it is associated with serious complications, including cardiovascular events and respiratory distress. The limited effectiveness of current pharmacological treatments for nicotine dependence underscores the urgent need for innovative and effective therapeutic approaches. Recent studies have shown that ivermectin, an antiparasitic agent, modulates the GABAergic, glutamatergic, and purinergic systems, which are implicated in the pathophysiology of addiction. This study aimed to examine the effects of ivermectin on the acquisition, extinction, and reinstatement of nicotine dependence in mice, utilizing the conditioned place preference (CPP) test, a widely recognized methodology in drug addiction research. Ivermectin (1 and 5 mg/kg, i.p.) was co-administered with nicotine (0.5 mg/kg, i.p.) over three consecutive days during the acquisition phase of nicotine dependence. In a separate experiment, the influence of ivermectin on the reinstatement of nicotine-induced CPP was assessed following an extinction period, using a single nicotine priming injection (0.1 mg/kg). Results indicated that ivermectin (1 and 5 mg/kg) significantly reduced the development of nicotine dependence (p < 0.05). Furthermore, ivermectin (5 mg/kg) facilitated the extinction of nicotine-induced CPP (p < 0.01) and attenuated the reinstatement of nicotine-induced CPP triggered by a priming dose of nicotine (p < 0.01). In contrast, administration of the lower dose of ivermectin (1 mg/kg) did not yield statistically significant effects on either the extinction or reinstatement phases (p > 0.05). Additionally, nicotine administration, alone or in combination with ivermectin at the tested doses, did not produce significant changes in motor coordination or locomotor activity. These findings suggest that ivermectin may attenuate both the acquisition and reinstatement of nicotine-induced CPP while facilitating the extinction of nicotine dependence. Collectively, the results indicate that ivermectin holds potential as a therapeutic agent in the treatment of nicotine addiction.

Allergic rhinitis (AR) is a prevalent chronic condition in childhood, and its increasing incidence has prompted research into potential associations with modifiable factors such as obesity. This meta-analysis aimed to assess the multivariate-adjusted relationship between childhood obesity and AR. A systematic search was conducted across PubMed, Embase, and Web of Science for observational studies that reported on the association between obesity and AR in children. Only studies that included multivariate adjustments for at least age and sex were considered. Random-effects models were employed to pool odds ratios (ORs) with 95% confidence intervals (CIs), accounting for heterogeneity. Fifteen cross-sectional studies comprising 23 datasets involving a total of 569,856 children were included in the analysis. The overall results indicated that obesity was not significantly associated with AR (adjusted OR: 1.04, 95% CI: 1.00-1.09; p = 0.08; I² = 24%). However, subgroup analyses revealed a significant association in Western countries (OR: 1.12, 95% CI: 1.00-1.24; p = 0.04; I² = 0%), while no significant association was found in Asian countries (OR: 1.04, 95% CI: 0.97-1.12; p = 0.27; I² = 52%). Notable associations were identified in studies utilizing national or international BMI cutoffs (OR: 1.06, 95% CI: 1.01-1.10; p = 0.02) and those with physician-diagnosed AR (OR: 1.07, 95% CI: 1.02-1.13; p = 0.006), but not in studies employing the 95th percentile BMI definition or ISAAC-based AR diagnosis. No significant differences were observed based on age or sex. Meta-regression analysis indicated that age, sex, and study quality score did not significantly influence the results (p all > 0.05). Egger's test revealed no evidence of publication bias (p = 0.43). In conclusion, while no significant overall association between childhood obesity and AR was found, subgroup analyses suggest potential links within specific populations and under particular methodological definitions. These findings should be interpreted with caution, and further longitudinal studies are necessary to determine whether preventive strategies aimed at reducing childhood obesity may also impact allergic outcomes.

Uterine leiomyomas are the most common benign tumors of the female genital tract, and alongside hormonal and genetic factors, emerging evidence implicates vitamin D deficiency in their pathogenesis. We investigated the association between serum 25-hydroxyvitamin D [25(OH)D] and the presence of uterine leiomyomas in women with unexplained infertility. In this retrospective case-control study, 148 women aged 18-45 years presenting to the Infertility Clinic of Ankara Bilkent City Hospital between July 2019 and February 2024 were included: 74 had imaging-confirmed leiomyomas (non-submucosal; FIGO types 4-6) and 74 infertile controls had no leiomyomas. Serum 25(OH)D was measured and demographic/clinical data were analyzed with appropriate parametric and non-parametric tests; correlations used Spearman's rho, and an ANCOVA adjusted for body mass index (BMI) and season assessed group differences. Groups were comparable in age and BMI (e.g., age 35.08 ± 5.79 vs 33.30 ± 5.57 years; p = 0.062). Mean serum 25(OH)D was significantly lower in women with leiomyomas than in controls (41.4 ± 23.7 vs 62.0 ± 34.2 nmol/L; p < 0.001), and this difference remained significant after adjustment for BMI and season (ANCOVA F = 10.7, p = 0.001). Vitamin D levels did not differ by leiomyoma number (single vs multiple: 44.1 ± 21.6 vs 38.5 ± 25.83 nmol/L; p = 0.32) or location (intramural vs subserosal: 40.7 ± 24.9 vs 43.1 ± 21.1 nmol/L; p = 0.69), and were not correlated with leiomyoma size (Spearman r = -0.04; p = 0.70). Among women with unexplained infertility, uterine leiomyomas are thus associated with significantly lower serum 25(OH)D levels, independent of BMI and season, whereas vitamin D status is unrelated to leiomyoma number, size, or location. These findings support a potential role of vitamin D deficiency in leiomyoma pathogenesis and underscore the need for larger, multicenter prospective studies to clarify causality and clinical implications.

Ischemia-reperfusion injury (IRI) presents a complex pathophysiology characterized by oxidative stress and inflammation. Arbutin, widely recognized for its use in skin whitening, also exhibits antioxidant, anti-inflammatory, and anticancer properties. This study aimed to assess the potential protective effects of arbutin at two different doses against IRI in the kidneys. Twenty-four male Wistar albino rats were randomly assigned to four equal groups: Control, IRI, 250 mg/kg arbutin + IRI (AR250+IRI), and 1000 mg/kg arbutin + IRI (AR1000+IRI). Arbutin was administered orally via gavage for 14 days to ensure sub-acute application. Following left kidney nephrectomy, ischemia was induced in the right kidney using a non-traumatic clamp for 45 minutes, succeeded by 60 minutes of reperfusion. Blood and tissue samples were subsequently collected for analysis. In the IRI group, levels of malondialdehyde, myeloperoxidase, interleukin-1 beta, and creatinine were significantly elevated; these levels decreased in the groups receiving arbutin supplementation. Notably, ischemia-modified albumin, urea, superoxide dismutase (inhibition ratio), and tumor necrosis factor alpha levels were reduced in the AR1000+IRI group. Additionally, decreased levels of catalase and glutathione peroxidase were observed in the AR1000+IRI group. Histopathological examination revealed flattening, necrosis, degeneration, dilation, glomerular necrosis, sclerosis, Bowman capsule dilation, and interstitial hemorrhage in the IRI group. The AR250+IRI group exhibited mild cortical-medullary congestion and a slight increase in glomerular size. Conversely, the AR1000+IRI group displayed a histological appearance resembling that of the control group. In conclusion, arbutin demonstrates potential protective effects against IRI. Its use may be recommended prophylactically for individuals at risk of developing IRI.

Nephrotic syndrome (NS) in children has been associated with an increased risk of early atherosclerosis, as indicated by carotid intima-media thickness (cIMT). However, the existing literature on the relationship between NS and cIMT in pediatric populations presents inconsistent findings. This meta-analysis aims to compare cIMT measurements between children with NS and healthy controls. A comprehensive search of PubMed, Embase, and Web of Science was conducted through May 22, 2025. Observational studies that compared cIMT in children under 18 years with NS against controls were included. Mean differences (MDs) with 95% confidence intervals (CIs) were aggregated using a random-effects model to account for potential heterogeneity. Thirteen case-control studies involving 578 children with NS and 741 controls were analyzed. The results indicated that children with NS had significantly higher cIMT compared to controls (MD: 0.06 mm; 95% CI: 0.04-0.08; p < 0.001; I² = 68%). Subgroup analyses revealed that the difference in cIMT was notably larger in studies with ≥ 60% male participants (MD: 0.09 mm) compared to those with < 60% males (MD: 0.03 mm; p for subgroup difference = 0.01). No significant differences were observed based on age, disease duration, or adjustments for body mass index, blood pressure, or lipid profile (all p > 0.05). Meta-regression analyses suggested that the proportion of male participants and the rate of steroid-resistant nephrotic syndrome (SRNS) may contribute to observed heterogeneity (adjusted R² = 29.8% and 22.5%, respectively), although the slopes for these meta-regressions were not statistically significant (p = 0.13 and 0.87). In conclusion, children with NS exhibit increased cIMT compared to controls, indicating early vascular changes. The predominance of males and the presence of SRNS may partially account for the heterogeneity observed across studies.

Procalcitonin (PCT) is classically a biomarker of bacterial infection, but its role in cardiovascular inflammation-particularly in coronary artery disease (CAD)-is less well defined. Evidence linking PCT with disease extent and outcomes across acute coronary syndrome (ACS) and chronic coronary syndrome (CCS) remains limited. We compared PCT levels among ACS, CCS, and angiographic controls; examined associations with inflammatory burden and anatomic complexity (SYNTAX score); and evaluated diagnostic performance and short- and intermediate-term prognostic value. In this single-center retrospective study, 477 consecutive adults undergoing diagnostic coronary angiography (December 2019-March 2020) were categorized as ACS (n=190), CCS (n=202), or controls with normal epicardial arteries (n=85). Demographic, laboratory, and angiographic data were collected. PCT was measured within 24 hours of admission. Multivariable logistic regression (using log10-transformed PCT) assessed independent associations with ACS and CCS. Correlations tested relationships with SYNTAX, C-reactive protein (CRP), and troponin-I. Receiver operating characteristic (ROC) analyses quantified discrimination. In ACS, outcomes were compared by PCT ≥0.25 ng/mL. Median PCT was higher in ACS and CCS than in controls (both p<0.001). Log10-PCT independently predicted disease presence in ACS (OR 4.30, 95% CI 2.00-9.20, p<0.001) and CCS (OR 2.81, 95% CI 1.43-5.54, p=0.003). In CCS, PCT correlated weakly but significantly with SYNTAX score (r=0.274, p=0.002); no meaningful correlations with SYNTAX, CRP, or troponin-I were observed in ACS. PCT showed moderate diagnostic accuracy (AUC 0.791 for ACS; optimal cut-off 0.25 ng/mL, sensitivity 82.4%, specificity 65.3%; and AUC 0.763 for CCS; optimal cut-off 0.30 ng/mL, sensitivity 89.4%, specificity 54.0%; all p<0.001). In ACS, PCT ≥0.25 ng/mL was not associated with higher in-hospital mortality, 1-year all-cause mortality, or major adverse cardiovascular events. PCT reflects inflammatory burden and the presence of CAD in both ACS and CCS and remains an independent predictor of disease presence, but its prognostic utility-particularly in ACS-is limited. PCT should complement, not replace, established biomarkers and anatomical scoring systems in clinical decision-making. Prospective, multicenter studies with serial PCT measurements are warranted to refine its clinical role.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease for which reliable early diagnostic biomarkers are still lacking. This study aimed to evaluate the diagnostic and monitoring value of induced sputum Krebs von den Lungen-6 (KL-6) levels in patients with IPF and to investigate their relationship with pulmonary function parameters and high-resolution computed tomography (HRCT) scoring. In this prospective observational study, 20 patients with IPF and 20 age-matched healthy subjects (HS) were enrolled between October 2021 and April 2023. Induced sputum samples were collected for KL-6 measurement using enzyme-linked immunosorbent assay, while all participants underwent pulmonary function testing and HRCT scoring. KL-6 levels were significantly higher in the IPF group compared with the HS group [776.29 (interquartile range, IQR: 681.98-858.57) vs. 322.21 (IQR: 253.67-338.64) U/mL, p<0.001]. In IPF patients, induced sputum KL-6 levels showed strong negative correlations with multiple lung function indices, including forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and diffusing capacity for carbon monoxide (DLCO) (all p<0.05), and a strong positive correlation with HRCT scores (r=0.908, p<0.001). Receiver operating characteristic (ROC) analysis demonstrated that combining KL-6 levels with HRCT scores yielded an area under the curve (AUC) of 0.936 (95% confidence interval, CI: 0.914-0.944), with specificity of 97.5% and sensitivity of 80.0%. In conclusion, induced sputum KL-6 levels reflect the degree of pulmonary fibrosis and are closely associated with functional and imaging indicators in IPF. The combination of KL-6 with HRCT scoring enhances diagnostic accuracy, underscoring its potential clinical utility as a noninvasive biomarker for early detection and monitoring of IPF.

Coronary heart disease (CHD) is a leading cause of morbidity and mortality; patients with type 2 diabetes mellitus (T2DM) are at particularly high risk, highlighting the need for reliable biomarkers for early detection and risk stratification. We investigated whether combining the stress hyperglycemia ratio (SHR) and systemic inflammation response index (SIRI) improves CHD detection in T2DM. In this retrospective cohort of 943 T2DM patients undergoing coronary angiography, associations of SHR and SIRI with CHD were evaluated using multivariable logistic regression and restricted cubic splines; robustness was examined with subgroup and sensitivity analyses. Discriminative performance was assessed by receiver operating characteristic (ROC) analysis and reclassification metrics (integrated discrimination improvement [IDI], net reclassification improvement [NRI]). Internal validation used bootstrapping, with calibration and discrimination yielding apparent and bias-corrected estimates. Of 943 patients, 600 had CHD. Multivariable models showed SHR (OR=1.68; 95% CI, 1.14-2.46; p=0.008) and SIRI (OR=2.17; 95% CI, 1.54-3.05; p<0.001) were independently associated with CHD, with nonlinear relationships (p for nonlinearity <0.05). Findings were consistent across subgroups and sensitivity analyses. The combined SHR-SIRI model achieved an AUC of 0.813 (95% CI, 0.783-0.843), outperforming SHR alone (AUC=0.773; 95% CI, 0.740-0.805) and SIRI alone (AUC=0.745; 95% CI, 0.713-0.778), and significantly improved NRI and IDI (p <0.05). All models showed strong discrimination and calibration. In conclusion, SHR and SIRI are independently associated with CHD in T2DM, and their combination enhances early identification of high-risk individuals.

Rheumatoid arthritis (RA) is a chronic autoimmune disease in which dysregulated interferon regulatory factor 5 (IRF5) may amplify pro-inflammatory pathways; prior genetic studies of IRF5 single-nucleotide variants (SNVs) in RA are inconsistent across populations and have not included mestizo Mexicans or evaluated rs59110799 in RA. We aimed to test whether four IRF5 SNVs (rs2004640G/T, rs2070197T/C, rs10954213G/A, rs59110799G/T) confer susceptibility to RA in women from Central Mexico. In a case-control study of 239 women with RA and 231 female controls (all self-identified Mexican-Mestizos, ≥3 generations), genotyping was performed by real-time PCR with TaqMan® probes; 80% of samples were duplicated (100% concordance) and control genotypes conformed to Hardy-Weinberg equilibrium. Association was assessed under allelic and multiple genetic models using logistic regression adjusted for age and birthplace, with Bonferroni correction for 23 tests (α=0.0022). Haplotype and linkage disequilibrium (LD) were analyzed with Haploview; putative functional effects were explored in silico (SNPinfo; GTEx). The minor alleles rs2004640T [OR=1.69, 95% CI 1.29-2.21; p=1.2×10⁻⁴], rs2070197C [OR=1.85, 1.39-2.46; p=2.0×10⁻⁵], and rs10954213A [OR=1.47, 1.12-1.93; p=0.002] were associated with increased RA risk after correction. Genotype-based associations were observed for rs2004640 (codominant and recessive) and rs2070197 (codominant, dominant, recessive). rs59110799G/T showed no significant association after correction (dominant model OR=1.69, 1.15-2.48; p=0.007). Nine haplotypes were identified; the haplotype carrying all four risk alleles (TCAT) was not associated, and two haplotypes with nominal signals (GCAG, TTGT) had control frequencies <1% and were excluded; variants were not in strong LD (r²<0.80). Our findings-providing the first evaluation of these IRF5 variants in Mexican women and the first report of rs59110799 in RA-support a role for IRF5 (rs2004640, rs2070197, rs10954213) in RA susceptibility in this Latin American population. Given the female-only design and moderate statistical power, replication and functional studies are warranted.