Biomolecules & biomedicine最新文献

Sepsis secondary to pneumonia is a prominent cause of intensive care unit (ICU) admissions and mortality among older adults, yet early bedside risk stratification poses significant challenges. This study aimed to evaluate the predictive value of the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the National Early Warning Score (NEWS), both individually and in combination, alongside admission serum lactate levels, for predicting mortality in geriatric ICU patients with pneumonia-related sepsis. In this single-center retrospective cohort study, we analyzed patients aged 65 years and older who were admitted between January 1, 2020, and July 1, 2025. Sepsis was defined according to Sepsis-3 criteria; APACHE II (using the worst values within the first 24 hours) and NEWS (measured at ICU admission) were recorded, along with the first lactate and other biomarkers obtained within the first 24 hours. We assessed mortality predictors using logistic regression and evaluated model discrimination through receiver operating characteristic (ROC) analysis. Among the 179 patients (median age 80), the ICU mortality rate was 64.8%. Non-survivors exhibited significantly higher APACHE II and NEWS scores, as well as elevated lactate and inflammatory markers (all p<0.001). In multivariable analysis, APACHE II (OR 1.130; p<0.001), NEWS (OR 1.239; p=0.003), and a history of stroke (OR 2.856; p=0.041) were identified as independent predictors of mortality, whereas lactate did not demonstrate independent predictive capability. Although lactate improved the discrimination of a baseline clinical-laboratory model (AUC increased from 0.67 to 0.75), it offered no incremental benefit when APACHE II and NEWS were included; the combined APACHE II+NEWS model achieved the highest AUC of 0.85. Exploratory cut-offs identified very high-risk subgroups (APACHE II >21 with NEWS >8 or lactate >2 mmol/L), with mortality rates approximating 86-87%. In conclusion, APACHE II and NEWS are robust early predictors of mortality in geriatric patients with pneumonia-related sepsis, while lactate may assist in early risk stratification but provides limited prognostic value beyond these scoring systems.

The assessment of visceral adipose tissue activity has gained significance in cardiac risk stratification. This study evaluates the predictive performance of novel visceral adiposity indices in determining the risk of postoperative atrial fibrillation in patients undergoing isolated coronary artery bypass grafting. Visceral adiposity indices were derived from anthropometric measurements and biochemical parameters collected during the preoperative period. The discriminative abilities of these indices were compared using receiver operating characteristic (ROC) curve analysis and their corresponding area under the curve (AUC) values. Univariate analysis revealed significant associations between the occurrence of postoperative atrial fibrillation and factors such as diabetes mellitus, a high EuroSCORE II, and extended cardiopulmonary bypass duration. Conversely, the visceral adiposity indices demonstrated substantial predictive value for postoperative atrial fibrillation. Notably, the cardiometabolic index (CMI) emerged as a significant predictor for the development of postoperative atrial fibrillation (OR: 4.054, 95% CI: 1.77-9.23; p=0.010). These findings indicate that CMI, a composite measure of visceral adiposity and metabolic dysfunction, may provide superior predictive performance for postoperative atrial fibrillation risk following isolated coronary artery bypass grafting compared to body mass index and visceral adiposity index, while showing comparable diagnostic value to the lipid accumulation product and body roundness index. Given the exploratory nature of this study, the suggested cutoff values should be interpreted cautiously and necessitate validation in diverse patient populations and larger cohorts prior to clinical implementation.

Prediabetes, characterized by impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or mildly elevated glycated hemoglobin (HbA1c), represents an intermediate metabolic state potentially contributing to cataract formation. However, the existing evidence for this association remains inconsistent. This meta-analysis aims to elucidate the relationship between prediabetes and cataract in adults. A systematic search was conducted across PubMed, Embase, Web of Science, CNKI, and Wanfang for observational studies assessing the association between prediabetes and cataracts in adults. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects models to account for heterogeneity. Subgroup analyses were performed based on study design, geographic region, diagnostic criteria for prediabetes, and covariate adjustment. Eight observational studies involving 22,342 participants were included in the analysis. Of these, 5,305 participants (23.7%) had prediabetes, and 7,625 participants (34.1%) had cataracts. Pooled results indicated that prediabetes was associated with a 34% increased odds of cataract compared to individuals with normoglycemia (OR = 1.34, 95% CI 1.11-1.61; p = 0.002; I² = 50%). Sensitivity analyses restricted to high-quality studies (NOS ≥ 7) produced consistent results (OR = 1.29, 95% CI 1.09-1.53; I² = 43%). The association remained significant across subgroups defined by geographic region, mean age, sex, diagnostic criteria for prediabetes, analytical models, and adjustment for sun exposure (all p > 0.05 for subgroup differences). In conclusion, this meta-analysis demonstrates a significant association between prediabetes and cataracts in adults. Given that most included studies were cross-sectional, these findings suggest a potential link rather than a causal relationship, highlighting the need for prospective research to clarify temporal relationships and underlying mechanisms.

Inflammation plays a significant role in the pathophysiology of atrial fibrillation (AF) and may affect the likelihood of AF recurrence following catheter ablation. The systemic immune-inflammation index (SII), calculated from circulating neutrophils, lymphocytes, and platelets, has emerged as a promising inflammatory biomarker. This meta-analysis aimed to assess the relationship between preprocedural SII and the recurrence of AF post-ablation. We conducted comprehensive searches across PubMed, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure (CNKI) for longitudinal observational studies reporting the correlation between preprocedural SII and AF recurrence after either radiofrequency or cryoballoon ablation. Risk ratios (RRs) were aggregated using random-effects models to account for heterogeneity. A total of ten cohort studies involving 4,045 patients were included in the analysis. Our findings indicate that a high preprocedural SII is significantly associated with an increased risk of AF recurrence (RR = 2.32, 95% CI 1.68-3.21; I² = 86%). This association remained robust across sensitivity analyses (RR range 2.07-2.53) and showed consistency across predefined subgroups based on sample size (<400 vs. ≥400), age (<61 vs. ≥61 years), sex distribution (<60% vs. ≥60% men), SII cutoff (<510 vs. ≥510), ablation modality (RFCA vs. CBA), follow-up duration (<20 vs. ≥20 months), and study quality (all p for subgroup differences >0.05), although these subgroup analyses were exploratory in nature. Meta-regression did not reveal significant study-level modifiers. Additionally, a further meta-analysis treating SII as a continuous variable demonstrated that each 100-unit increase in SII correlates with a higher recurrence risk (RR = 1.09, 95% CI 1.04-1.13; I² = 43%). In conclusion, elevated preprocedural SII is associated with an increased risk of AF recurrence after catheter ablation, indicating that SII may serve as a potential adjunctive marker of inflammatory status, pending further prospective validation.

The prognostic value of systemic inflammatory and nutritional biomarkers in patients with locally advanced rectal cancer (LARC) remains inadequately defined. This multicenter retrospective study comprehensively assessed the prognostic performance of twelve inflammation-based indices, aiming to identify the most informative biomarker for patients undergoing neoadjuvant chemoradiotherapy followed by surgery. We analyzed data from 427 patients with stage II-III LARC treated at three medical centers between 2010 and 2021. Twelve biomarkers, derived from routine pretreatment blood parameters-including hemoglobin, albumin, neutrophils, lymphocytes, monocytes, and platelets-were evaluated for their association with overall survival (OS) and disease-free survival (DFS). The prognostic performance was measured using the concordance index (C-index), time-dependent area under the receiver operating characteristic curve (time-AUC), and Brier score. Among the evaluated biomarkers, the hemoglobin-albumin-lymphocyte-platelet (HALP) score exhibited robust and consistent prognostic performance. For OS, HALP achieved a C-index of 0.687 and a time-AUC of 0.668, along with the lowest Brier score (0.134); similar results were observed for DFS (C-index 0.675, time-AUC 0.665). Patients with low HALP scores had significantly worse OS and DFS compared to those with high HALP scores. Multivariate Cox regression analysis confirmed low HALP as an independent risk factor for OS (HR = 3.937, 95% CI: 2.445-6.329; p < 0.001) and DFS (HR = 2.212, 95% CI: 1.577-3.096; p < 0.001). Nomograms integrating HALP with key clinicopathological variables provided incremental prognostic value, demonstrating good discrimination and calibration at 12, 36, and 60 months. These findings indicate that HALP is a simple and cost-effective biomarker for prognostic stratification in LARC.

Nutritional status significantly influences treatment tolerance and long-term outcomes in patients with locally advanced rectal cancer (LARC); however, individual nutritional markers may not fully capture overall nutritional reserves. This study aimed to evaluate the prognostic value of a comprehensive nutritional index (CNI), derived from principal component analysis, in patients with LARC undergoing neoadjuvant chemoradiotherapy (NCRT) followed by surgical intervention. We conducted a retrospective analysis of 336 patients with LARC who received NCRT followed by surgery between 2014 and 2019. The CNI was constructed using body mass index, usual body weight percentage, total lymphocyte count, serum albumin, and hemoglobin levels. Patients were categorized into low- and high-CNI groups based on an outcome-oriented cut point, and survival outcomes were assessed through Kaplan-Meier analysis and Cox regression. Patients with lower CNI scores exhibited significantly poorer overall survival and disease-free survival compared to those with higher CNI scores. Furthermore, CNI remained independently associated with both endpoints after adjusting for established pathological factors, including tumor regression grade and ypN stage. A nomogram that integrates CNI, tumor regression grade, and ypN stage demonstrated favorable discrimination and calibration during internal validation. These findings support the use of pretreatment CNI as a practical nutritional composite associated with prognosis in LARC patients treated with NCRT, and the proposed nomogram may enhance individualized risk estimation.

Progesterone and adiponectin receptor 3 (PAQR3) is a Golgi-localized seven-transmembrane protein that anchors rapidly accelerated fibrosarcoma kinase (Raf) and suppresses rat sarcoma/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (Ras/Raf/MEK/ERK) signaling, thereby influencing cellular proliferation, differentiation, and metastasis. This review aims to summarize the expression patterns, regulatory mechanisms, key downstream pathways, and clinical significance of PAQR3 in cancer. We synthesized findings from published clinical and experimental studies, including in vitro assays and nude mouse xenograft models, that evaluate PAQR3 expression, function, and signaling interactions across various tumor types. Overall, PAQR3 is frequently downregulated in many cancers, potentially due to promoter methylation, and low expression levels are associated with adverse clinicopathologic features and reduced survival. Functionally, PAQR3 overexpression inhibits proliferation, colony formation, migration, invasion, and tumor growth, primarily through the inhibition of extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathways and modulation of epithelial-mesenchymal transition (EMT). Additionally, PAQR3 is linked to nuclear factor kappa B/tumor protein p53 (NF-κB/p53), epidermal growth factor/beta-catenin (EGF/β-catenin) signaling, autophagy, and nuclear factor erythroid 2-related factor 2/ferroptosis (Nrf2/ferroptosis). These effects are modulated by upstream regulators, including microRNA-543 (miR-543), circular RNA 0043280/microRNA-203a-3p (circ_0043280/miR-203a-3p), microRNA-15b (miR-15b), human epidermal growth factor receptor 2 (HER2), 5-aza-2'-deoxycytidine (5-Aza-CdR), autophagy-related 7 (ATG7), and damage-specific DNA binding protein 2 (DDB2). In conclusion, PAQR3 functions as a tumor suppressor and holds potential as a prognostic biomarker. Targeting PAQR3-related pathways may provide new therapeutic opportunities.

Immunotherapy, a therapeutic strategy aimed at modulating the host immune system, has undergone rapid evolution over recent decades, particularly in oncology. Advanced methodologies, including immune checkpoint inhibition, cytokine therapy, chimeric antigen receptor T-cell therapy (CAR-T), and tumor-infiltrating lymphocyte therapies, have significantly transformed cancer treatment. This review summarizes recent advancements in immunotherapy and examines its expanding applications across a range of diseases, such as autoimmune disorders, infectious diseases, transplant rejection, and allergic conditions. A structured literature search was conducted using PubMed and Google Scholar, prioritizing studies published from 2015 to 2026. The findings underscore the efficacy of monoclonal antibodies, adoptive cell therapies, cytokine modulation, and checkpoint-targeted strategies beyond oncology. However, challenges remain, including variable patient responses, immune-related adverse events, and treatment costs. This review also explores the emerging role of artificial intelligence (AI) in enhancing personalized immunotherapy through patient stratification, biomarker identification, and predictive modeling. The integration of multi-omics data with AI presents promising opportunities for improving treatment efficacy and safety, although issues related to data quality, interpretability, regulatory frameworks, and ethical considerations must be addressed. In conclusion, immunotherapy is rapidly extending beyond cancer, and AI-supported personalized approaches offer a promising pathway to safer, more effective, and broadly applicable treatments.

The escalating crisis of antimicrobial resistance (AMR) among Gram-negative pathogens, particularly Klebsiella pneumoniae (KP), necessitates innovative strategies to enhance the efficacy of existing antibiotics. Synergistic drug combinations present a promising approach to improve therapeutic outcomes and delay the emergence of resistance. This study investigates the synergistic interaction between the natural alkaloid berberine chloride and the repurposed antibiotic rifaximin against KP. Integrated in vitro and in silico analyses reveal significant bactericidal synergy between the two agents, mediated through concurrent inhibition of the transcriptional anti-termination factor RfaH, a key regulator of virulence and capsule biosynthesis. Molecular docking and dynamics simulations demonstrate that both compounds cooperatively bind to the RfaH pocket, stabilizing an inactive ternary complex without major structural disruption. Functional assays confirm that the combination effectively suppresses RfaH-dependent capsule production at lower concentrations compared to monotherapy. These findings suggest that RfaH is a viable target for combinatorial inhibition and provide a plausible mechanistic foundation for the berberine-rifaximin synergy. This work supports the rational development of dual-targeting anti-virulence strategies to combat multidrug-resistant KP infections.

Fecal DNA methylation of the syndecan-2 (SDC2) gene is being explored as a noninvasive biomarker for colorectal cancer (CRC) detection. However, its diagnostic performance necessitates thorough evaluation. A systematic search of PubMed, Embase, and Web of Science was conducted to identify studies investigating fecal SDC2 methylation (mSDC2) for CRC diagnosis. Eligible studies included adult CRC patients with histological confirmation and controls with either normal mucosa or benign colorectal lesions. Pooled sensitivity and specificity were synthesized using a Reitsma bivariate random-effects model, and summary receiver operating characteristic (SROC) curves with corresponding area under the curve (AUC) values were derived from this hierarchical model. Twenty-five studies encompassing 3,427 CRC patients, 3,267 individuals with benign lesions, and 5,372 with normal mucosa were included. For the comparison of CRC versus normal mucosa (24 studies), the pooled sensitivity and specificity were 0.86 (95% confidence interval [CI]: 0.82-0.89; I² = 88%) and 0.93 (95% CI: 0.90-0.95; I² = 95%), respectively. The pooled diagnostic odds ratio (DOR) was 81.73 (95% CI: 51.60-129.46), with an AUC of 0.95 (95% CI: 0.93-0.97). In the comparison against benign lesions (22 studies), the sensitivity was 0.85 (95% CI: 0.81-0.89; I² = 87%), specificity was 0.66 (95% CI: 0.59-0.71; I² = 91%), DOR was 11.10 (95% CI: 7.61-16.19), and AUC was 0.83 (95% CI: 0.80-0.86). Deeks' funnel plot asymmetry tests indicated no statistically significant publication bias (p = 0.48 and 0.54). In conclusion, fecal mSDC2 testing demonstrates high diagnostic accuracy for CRC detection when compared to individuals with normal mucosa and moderate performance against benign colorectal lesions. These findings suggest that mSDC2 may serve as a promising noninvasive biomarker to complement existing CRC screening methodologies.