Biomolecules & biomedicine最新文献

Tubeless uniportal video-assisted thoracoscopic surgery (VATS) is an innovative approach characterized by the use of non-intubated (spontaneous-breathing) anesthesia, the omission of routine postoperative chest drainage, and single-port access. This technique has gained traction in recent years for a variety of thoracic procedures. While practices reported in the literature may differ, this review primarily examines the combined non-intubated and drainless approach. This narrative review provides a comprehensive overview and critical analysis of its current clinical applications, including sympathectomy, pulmonary wedge resection, spontaneous pneumothorax, thymectomy, and early-stage lung cancer. It also addresses essential aspects of perioperative management and procedural indications within enhanced recovery-oriented pathways. A systematic literature search of PubMed, Embase, and Web of Science was conducted to identify pertinent studies published between January 2010 and April 2025. Current clinical reports indicate potential benefits such as reduced postoperative pain, shorter hospital stays, and accelerated recovery. However, the existing evidence largely stems from small, observational studies with varied methodologies, necessitating cautious interpretation. The broader implementation of this technique in more complex procedures depends on the establishment of standardized clinical pathways, the refinement of multidisciplinary perioperative strategies, and validation through multicenter prospective studies. Tubeless uniportal VATS shows promise as a significant advancement in function-preserving and recovery-oriented thoracic surgery.

Rheumatoid arthritis (RA) exhibits significant inter-patient variability in response to and toxicity from methotrexate (MTX). The clinical utility of erythrocyte methotrexate polyglutamates (MTXPGs) and MTX-pathway pharmacogenetics remains uncertain. This study investigates the relationships between MTX-pathway gene polymorphisms, erythrocyte MTXPG levels, and MTX treatment outcomes in RA. In a single-center, cross-sectional cohort study conducted in southern Fujian from 2017 to 2020, we analyzed 140 Han Chinese RA patients who had been receiving stable low-dose oral MTX (7.5-15 mg/week) for at least three months. Genotyping was performed using MassARRAY, and MTXPG levels 1-6 were quantified in red blood cells via LC-MS/MS. Data on treatment efficacy (measured by ACR20 and clinical scales) and MTX-related adverse drug reactions (ADRs) were collected, with associations analyzed through univariate and multivariable models. MTXPG levels 1-3 were detectable in all patients, while longer-chain MTXPGs were infrequent. The SLCO1B1 521T>C polymorphism was independently associated with lower levels of MTXPG1 (B=-1.119), MTXPG2 (B=-0.924), and total MTXPG (B=-0.849), all with P-values ≤0.045. However, MTXPG levels did not correlate with MTX efficacy or ADRs. The GGH 401C>T polymorphism was associated with a reduced ACR20 response (OR=0.421, p=0.021) and higher visual analog scale (VAS) and patient global assessment (PGA) scores. Additionally, the variants SLCO1B1 521T>C and ABCB1 3435C>T were linked to higher scores in the Patient Health Global Assessment (PHGA) and Health Assessment Questionnaire (HAQ). In this low-dose MTX cohort, erythrocyte MTXPGs did not predict clinical outcomes. However, variants in SLCO1B1, GGH, and ABCB1 emerged as exploratory candidate markers for MTX response, warranting validation in larger prospective cohorts.

Autoimmune diseases are becoming increasingly prevalent and can cause multi-organ damage through dysregulated immune responses to self-antigens. This review aims to summarize the roles of annexin family proteins and annexin autoantibodies in the mechanisms of autoimmune diseases, as well as their potential diagnostic and therapeutic applications. A targeted PubMed search conducted on August 31, 2025, utilized annexin- and disease-related terms without year restrictions, focusing on English-language, peer-reviewed studies involving humans or recognized animal models. Evidence suggests that Annexin A1 (ANXA1) and formyl peptide receptor 2 (FPR2) signaling can influence inflammatory and T-cell responses. Additionally, Annexin A2 (ANXA2) is associated with organ-targeted injury, such as lupus nephritis (LN) in systemic lupus erythematosus (SLE), through its interactions with anti-double-stranded DNA antibodies (anti-dsDNA). Annexin A5 (ANXA5) serves as an anticoagulant phospholipid "shield," which can be compromised by antiphospholipid antibodies (aPLs), contributing to thrombosis and obstetric complications in antiphospholipid syndrome (APS) and increasing vascular risk in SLE. In rheumatoid arthritis (RA), ANXA1 exhibits context-dependent effects, while ANXA2 promotes synovial proliferation, invasion, and angiogenesis. Dysregulation of annexins has also been observed in primary Sjögren's syndrome (pSS), multiple sclerosis (MS), and systemic sclerosis (SSc). Additionally, the emerging utility of anti-ANXA1, anti-ANXA2, and anti-ANXA5 autoantibodies for phenotyping and risk stratification, including in seronegative antiphospholipid syndrome (SNAPS), highlights their clinical relevance. Overall, annexins and their autoantibodies represent promising biomarkers and therapeutic targets; however, the heterogeneity of assays and the limited availability of prospective multicenter data currently hinder clinical translation.

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.