Biomolecules & biomedicine最新文献

The COVID-19 pandemic revealed significant variability in mechanical ventilation training and bedside practices, highlighting the necessity for standardized, actionable protocols. This study aimed to develop the Standard Training and Operating Procedure (STOP), an evidence-based algorithm designed for managing mechanically ventilated critically ill patients and troubleshooting patient-ventilator interactions. Utilizing the Successive Approximation Model (SAM), we reviewed current guidelines and expert recommendations, created a minimum-viable prototype during a multidisciplinary "savvy start," and refined it through seven iterative review cycles involving 33 frontline clinicians. The finalized tool underwent external evaluation via a Modified-Delphi process within the Checklist for early recognition and treatment of acute illness and injury (CERTAIN) network, engaging 50 clinicians from 19 countries across four continents, with a consensus threshold of ≥70%. STOP consists of eight sequential bedside checkpoints: abnormal vital signs/ventilator alarms, assessment of ventilation adequacy, elevated peak pressure, elevated plateau pressure, lung protection against ventilator-induced lung injury, risk of oxygen toxicity, patient-ventilator asynchrony, and readiness for spontaneous awakening and breathing trials. The Delphi agreement across these steps ranged from 82% to 96%, supporting the tool's face validity and clinical relevance. STOP offers a practical framework to minimize practice variability and enhance the safety of mechanical ventilation; however, prospective implementation studies are necessary to assess its impact on adherence and patient outcomes.

Cell-free DNA (cfDNA) biomarkers derived from Arthrobacter luteus (ALU) repeats and long interspersed nuclear elements 1 (LINE1) - including ALU-115, ALU-247, LINE1-97, and LINE1-266 concentrations, as well as the integrity ratios ALU-247/115 and LINE1-266/97 - are commonly utilized to assess cfDNA quantity and integrity. This study examined the impact of delayed blood processing and prolonged plasma storage on these biomarkers using quantitative polymerase chain reaction. Blood samples were collected from twelve healthy individuals (6 males; mean age, 65.8 ± 4.69 years) into dipotassium ethylenediaminetetraacetic acid tubes. Plasma cfDNA was extracted after various storage durations and temperatures, with aliquots from immediately processed blood subsequently stored at -80°C for different time intervals. Except for LINE1-97, most biomarkers showed significantly higher levels in plasma isolated from whole blood stored at room temperature compared to plasma processed immediately. Storage at 4°C resulted in fragment-specific effects: ALU-247/115 levels remained stable at 3 hours but decreased at 6 hours, while LINE1-266/97 levels increased at both time points. For plasma stored at -80°C, ALU-derived biomarkers remained stable for up to 12 months; however, LINE1-97 levels significantly declined, accompanied by a corresponding increase in LINE1-266/97 as early as one month after freezing. These findings indicate that both storage duration and temperature significantly impact the measured levels of ALU- and LINE1-derived cfDNA biomarkers. Consequently, standardization of pre-analytical handling of blood and plasma is crucial for studies evaluating cfDNA quantity and integrity.

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer mortality worldwide; however, precision oncology has fundamentally transformed its treatment landscape. In 2025, seven approvals by the U.S. Food and Drug Administration (FDA) further accelerated biomarker-driven care across critical molecular subsets. These include MET-directed and trophoblast cell-surface antigen-2 (TROP-2) antibody-drug conjugates (ADCs), expanded strategies targeting epidermal growth factor receptor (EGFR), notably those addressing exon 20 insertion mutations, a ROS proto-oncogene 1 (ROS1) inhibitor, and various human epidermal growth factor receptor 2 (HER2) options that encompass both tumor-agnostic and mutation-selected approaches. These advancements underscore the necessity for integrated diagnostics-such as next-generation sequencing (NGS), fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC)-while also emphasizing ongoing challenges in biomarker selection, therapeutic sequencing, and equitable global implementation.

Clinical data regarding the interaction between tubular functional capacity (TFC) and maladaptive parathyroid gland response in early-stage chronic kidney disease (CKD) are limited. This study aimed to evaluate the association between parathyroid gland response, measured as intact parathyroid hormone (iPTH) serum concentration (pg/mL) using chemiluminescent microparticle immunoassay, and the dissociation between the decline in glomerular filtration rate (GFR) and TFC, assessed through radionuclide clearances. TFC was evaluated by measuring effective renal plasma flow (mERPF, ml/min/1.73m²) using (131I) Hippurate (131I-H) clearance, while GFR was measured using (99m) Tc-DTPA (mGFR, ml/min/1.73m²). Consecutive participants with preexisting CKD (N=111, female 44%, male 56%) were enrolled and stratified into four groups based on CKD stages (1, 2, 3a, and 3b). Median serum iPTH concentrations significantly differed between Stage 1 [23 (20.4-25.5) pg/mL] and Stage 2 [23.6 (20.5-26.8) pg/mL] compared to Stage 3a [38.1 (34.1-41.9) pg/mL] and Stage 3b [45.8 (39.7-51.9) pg/mL] (p=0.01). In Stage 1, there was a significant positive association between iPTH and mERPF (p=0.003). Conversely, in Stage 3b, iPTH was significantly negatively associated with both mGFR and mERPF (p<0.05 for both). Regression models that included the interaction between CKD stage and either mGFR or mERPF, alongside other predictors (age, CKD stage, body mass index, ionized calcium, and 25-hydroxyvitamin D), revealed significant associations with iPTH (p<0.05 for all variables). The assessment of TFC using 131I-H plasma clearance does not enhance the detection of maladaptive parathyroid gland responses compared to evaluating CKD stage and its relationship with declining glomerular and tubular clearances in early-stage CKD patients.

Laryngopharyngeal reflux (LPR) has been implicated in the pathogenesis of chronic rhinosinusitis (CRS), but the evidence from individual studies remains inconsistent. This meta-analysis aims to clarify the association between LPR and CRS in adults. We systematically searched PubMed, Embase, Web of Science, CNKI, and Wanfang for observational studies that evaluate the relationship between LPR and CRS in adult populations. Heterogeneity among studies was assessed using the Cochrane Q test and the I² statistic. Odds ratios (ORs) and 95% confidence intervals (CIs) were pooled using a random-effects model to account for heterogeneity. A total of eight cross- sectional studies involving 3,456 participants were included in the analysis. The results indicated a significant association between LPR and a higher prevalence of CRS in adults (OR = 4.77, 95% CI 2.51 to 9.07; p < 0.001; I² = 63%). Sensitivity analysis restricted to high-quality studies (Newcastle-Ottawa Scale score ≥ 7) produced similar results with no observed heterogeneity (OR = 5.98, 95% CI 3.60 to 9.92; I² = 0%). Exploratory subgroup analyses suggested a stronger association in studies with smaller sample sizes and when both LPR and CRS were diagnosed using objective methods. No significant evidence of publication bias was detected through Egger's test (p = 0.35); however, this analysis was underpowered and should be interpreted cautiously in the context of the small-study effect. In conclusion, LPR may be associated with an increased prevalence of CRS in adults, especially when both conditions are diagnosed using objective criteria. Further prospective studies are needed to confirm this association and explore the underlying mechanisms.

This response addresses feedback on our systematic review and meta-analysis comparing sugammadex with neostigmine for neuromuscular block reversal. We acknowledge high heterogeneity for time-based outcomes, likely due to differences in clinical settings and anesthetic/surgical protocols, but pooled effects consistently favored sugammadex for faster and more complete reversal. We agree hypnotic depth and other perioperative factors may modify emergence and airway safety, yet these variables were inconsistently reported and could not be analyzed quantitatively. We also clarify that time outcomes were synthesized using standardized mean differences to account for different reporting units, and any presentation inconsistencies will be corrected. Overall, our findings support pharmacologic superiority of sugammadex with reductions in selected complications, while emphasizing that broader recovery quality may not uniformly improve and should be interpreted in clinical context.

Heart failure (HF) remains a leading cause of global mortality, underscoring the urgent need for reliable, minimally invasive biomarkers to facilitate early diagnosis and risk stratification. MicroRNA-21 (miR-21) has been implicated in cardiac fibrosis, hypertrophy, and the progression of HF; however, its clinical utility remains uncertain. This study presents a systematic review and diagnostic test accuracy (DTA) meta-analysis aimed at assessing the diagnostic and prognostic performance of circulating miR-21 in HF. We estimated pooled sensitivity, specificity, and area under the curve (AUC) for the DTA analysis, and synthesized hazard ratios (HRs) with 95% confidence intervals (CIs) for prognostic outcomes. Additionally, univariate meta-regression was conducted to explore demographic and clinical moderators. Our analysis included fourteen studies with a total of 1,327 participants. Results demonstrated that circulating miR-21 levels were significantly elevated in HF patients compared to controls (fold change 1.61; 95% CI 1.46-1.78; p < 0.001). The diagnostic accuracy was notably high, with a sensitivity of 0.94 (95% CI 82.0-98.0), specificity of 0.90 (95% CI 79.0-96.0), and AUC of 0.97 (95% CI 96.0-98.0). Elevated levels of miR-21 were associated with an increased risk of worsening HF severity (HR 1.84; 95% CI 1.14-2.97; p=0.01) and HF-related cardiovascular death (HR 2.00; 95% CI 1.30-3.03; p=0.001). However, no significant association was found with HF-related hospitalization (HR 0.97; 95% CI 0.61-1.52; p=0.88). Variability in sample type and differing clinical thresholds contributed to heterogeneity across studies. These findings support the potential of circulating miR-21 as a diagnostic and prognostic biomarker for HF. Nevertheless, further research with standardized sample sizes and clinical thresholds is necessary to establish robust evidence for its clinical application.

Myocardial ischemia-reperfusion (IR) injury remains a major challenge in cardiac surgery, and comparative histological and ultrastructural data on cardioplegia solutions are limited. This study compared the myocardial protective effects of St. Thomas II and del Nido cardioplegia in a controlled rat IR model, focusing on inflammation, mast cell dynamics, and subcellular preservation. Twenty-four Wistar Albino rats were randomized to Control, St. Thomas II, or del Nido groups. After 90 minutes of ischemia and 30 minutes of passive reperfusion, myocardial tissue was analyzed by hematoxylin-eosin, toluidine blue, and transmission electron microscopy. Outcomes included mast cell counts, leukocyte infiltration, karyolysis, and ultrastructural measures (Flameng score, crista density, basement membrane thickness). Both cardioplegia groups preserved myocardial morphology and attenuated inflammatory changes versus control. Light microscopy revealed a consistent mast cell density and reduced karyolysis in hearts treated with cardioplegia, with no significant differences observed between St. Thomas II and del Nido solutions. Conversely, transmission electron microscopy (TEM), the primary endpoint of this study, demonstrated enhanced mitochondrial and endothelial preservation in the del Nido group, as evidenced by significantly lower Flameng scores and increased crista density compared to both St. Thomas II and control groups (p < 0.05). In conclusion, both solutions reduced early IR-related injury, but del Nido provided a significant ultrastructural advantage on TEM despite similar routine light-microscopic findings.

This correspondence comments on the systematic review and meta-analysis by Zhu and Li comparing sugammadex with neostigmine for neuromuscular block reversal and postoperative outcomes. While the authors provide a useful synthesis suggesting faster recovery and less residual blockade with sugammadex, several issues may limit the validity and clinical generalizability of the pooled conclusions. Many key outcomes show extreme heterogeneity (I² frequently >90%), raising concerns that combined estimates may obscure clinically important variation in anesthetic technique, blockade depth, monitoring, and recovery protocols. In particular, emergence safety depends not only on neuromuscular indices (e.g., TOF ≥0.9) but also on hypnotic depth at the time of reversal; evidence indicates that volatile anesthetic concentration (MAC) can meaningfully modify airway obstruction risk after sugammadex. Additionally, inconsistencies in the reporting of time-based effect sizes, specifically between standardized mean differences (SMD) and mean differences (MD) with identical values, necessitate clarification to enhance interpretability. We highlight the need for more cautious interpretation, targeted subgroup analyses incorporating anesthetic depth and other effect modifiers, and more robust meta-analytic methods to strengthen precision and applicability of the findings.

Caffeine is one of the most widely consumed psychoactive stimulants, primarily functioning as a non-selective adenosine receptor antagonist. Its increasing detection in wastewater and surface waters reflects extensive anthropogenic use. This review synthesizes evidence from zebrafish (Danio rerio)-a genetically tractable vertebrate with rapidly developing external embryos-to assess the impact of caffeine exposure across environmentally relevant (ng-µg/L) and pharmacological/toxicological (mg/L and above) concentrations on early development and neurobehavior. Behavioral studies indicate dose- and stage-dependent alterations in locomotion, anxiety-like responses, memory performance, and sleep patterns, suggesting disruptions in neural circuitry and stress-axis regulation. Biochemical analyses frequently reveal oxidative imbalances characterized by increased reactive oxygen species and lipid peroxidation, alongside changes in antioxidant defenses (e.g., glutathione levels, superoxide dismutase (SOD) activity, and glutathione reductase activity). These findings support oxidative stress as a potential mechanistic hub, although a causal relationship has yet to be established. Embryonic exposure to caffeine is associated with developmental toxicity, including delayed hatching and concentration-dependent malformations such as edema, axial deformities, impaired angiogenesis, and neuromuscular defects at higher doses. However, cross-study comparisons are hindered by variations in units, exposure durations, and assay protocols. In summary, caffeine disrupts behavior, redox homeostasis, and developmental processes in zebrafish, highlighting the necessity for standardized methodologies to identify stage-specific vulnerabilities.