International Journal of Medical Sciences最新文献

Background: Community-acquired pneumonia (CAP) is associated with marked immune dysregulation, but the peripheral T-cell transcriptional alterations linked to CAP remain incompletely defined. We aimed to characterize CAP-associated T-cell heterogeneity and identify candidate blood biomarkers by integrating single-cell and bulk transcriptomic data.

Methods: GEO-processed whole-blood microarray expression data from 108 patients with CAP and 42 healthy controls (GSE65682), together with processed PBMC scRNA-seq data from five non-influenza CAP donors and four control donors (GSE164948), were analysed. Cell annotation, differential expression, disease contribution scoring, LASSO regression, and support vector machine-recursive feature elimination were used to identify candidate genes. Immune infiltration, enrichment, and pseudotime analyses were performed. Key findings were evaluated by qRT-PCR in PBMCs from an independent cohort of 36 CAP patients and 18 healthy controls.

Results: T cells showed the highest disease contribution score and were enriched for pathways related to antigen processing, phosphorylation, and immune regulation. Four candidate biomarkers, CD8B, GZMM, MYL12B, and TUBA1A, showed differential expression between CAP and controls. CIBERSORT suggested increased eosinophils and monocytes and reduced resting CD4+ memory T cells in CAP. Pseudotime analysis indicated that CAP-associated T cells accumulated at higher inferred pseudotime values. qRT-PCR confirmed significant upregulation of these four candidate biomarkers in CAP PBMCs; FCGR2A also showed CAP-associated expression changes.

Conclusions: Integrative transcriptomic profiling identified peripheral T-cell dysregulation in CAP and highlighted CD8B, GZMM, MYL12B, and TUBA1A as candidate blood biomarkers. These findings provide a basis for further multicenter validation and mechanistic studies.

Background: Red blood cell distribution width (RDW) has emerged as a potential biomarker associated with adverse outcomes in various diseases. However, its clinical significance in neonatal surgical populations remains unclear. The present study aimed to investigate the association between early postoperative RDW and postoperative outcomes in neonates undergoing non-cardiac surgery.

Methods: This retrospective cohort study included neonatal patients who underwent non-cardiac surgery at a tertiary children's hospital. Patients were stratified into quintiles based on early postoperative RDW levels: Q1 (extremely low), Q2 (low), Q3 (moderate), Q4 (high) and Q5 (extremely high). The primary outcome was postoperative length of hospital stay (LOS). Secondary outcomes included 30-day mortality, duration of postoperative mechanical ventilation and ICU stay, and postoperative complications. Multivariable regression analyses were performed to assess associations. Propensity score matching (PSM) comparing the higher-RDW group with the lower-RDW group was performed to further account for baseline confounding.

Results: A total of 1,014 neonates were included in this study. The RDW quintile cutoffs were defined as follows: Q1 (< 14.5%), Q2 (14.5-15.0%), Q3 (15.1-15.7%), Q4 (15.8-17.1%) and Q5 (> 17.1%). Neonates in the higher quintiles had significantly higher risks for prolonged LOS (Q4: adj. OR 2.516, [95% CI 1.217-5.204]; Q5: adj. OR 5.854, [95% CI 2.606-13.146]; p for Trend < 0.001). After PSM, the increased risk of prolonged LOS remained significant for neonates in the higher-RDW group (Q4-Q5), with an adjusted OR of 3.805 (95% CI 1.998-7.245, p < 0.001) in the matched cohort. When analyzed as a continuous variable, early postoperative RDW remained positively associated with LOS (p = 0.020). This association was consistent across subgroups and sensitivity analyses. For secondary outcomes, the association was also observed in prolonged ICU stay, acute kidney injury and acidosis (all p < 0.05) but there was no difference in 30-day mortality.

Conclusions: Elevated RDW within 24 hours after non-cardiac surgery is significantly associated with prolonged LOS and increased risk of postoperative complications in neonates. RDW may serve as a clinically accessible biomarker for postoperative risk stratification in this population.

Background: Discordance between glycated hemoglobin (HbA1c) levels and blood glucose is commonly observed in clinical practice. The hemoglobin glycation index (HGI) has been proposed as a measure to quantify individual variations in glycation. Our study aimed to investigate the association between HGI and glucose variability assessed by continuous glucose monitoring (CGM) in patients with type 2 diabetes (T2D) treated with metformin monotherapy.

Methods: Adults with T2D treated with metformin monotherapy (daily dose ≥ 1500 mg) who had HbA1c levels ≥ 7.0% (n = 100; mean age 54.0 ± 8.2 years; 52.0% female) undergoing CGM were analyzed. Predicted HbA1c was derived from linear regression of HbA1c on fasting plasma glucose, and the HGI was calculated as observed HbA1c minus predicted HbA1c. CGM metrics-including standard deviation, coefficient of variation, mean amplitude of glycemic excursions (MAGE), and time in ranges-were analyzed to evaluate their associations with HGI.

Results: HGI was significantly associated with mean sensor glucose (β = 13.60, 95% CI 5.16-22.04, p = 0.002) and CGM-derived glucose variability metrics, including standard deviation (β = 7.53, 95% CI 4.49-10.58, p < 0.001), coefficient of variation (β = 2.22, 95% CI 0.29-4.15, p = 0.025), and MAGE (β = 22.14, 95% CI 14.59-29.69, p < 0.001). These associations remained significant after multivariable adjustment. HGI was also negatively associated with time in range (β = -7.29, 95% CI -12.79 to -1.79, p = 0.010) and positively associated with time above range (β = 7.35, 95% CI 1.69-13.01, p = 0.011).

Conclusion: These findings highlight a significant association between HGI and glucose variability from CGM, suggesting that HGI may serve as a complementary marker in diabetes management.

Gastrointestinal stromal tumors (GISTs) are the most common sarcomas of the alimentary tract and are primarily characterized by malignant progression, a major cause of mortality. AT-rich interaction domain 1A (ARID1A), a core component of the chromatin-remodeling SWI/SNF complex, has been found to correlate with GIST tumor grade, although the underlying mechanism remains unclear. Its frequent inactivation across diverse cancer types reveals pleiotropic roles that intersect multiple hallmarks of cancer. In this study, we aimed to investigate the potential relationship between ARID1A and malignant progression in GISTs, as well as the underlying mechanism. Western blotting, real-time polymerase chain reaction, and immunohistochemistry were used to assess ARID1A expression in GIST tissues. Cell Counting Kit-8 (CCK-8) assays were performed to evaluate cell proliferation. Wound-healing and Transwell assays were conducted to assess cell migration and invasion. Flow cytometry was used to analyze apoptosis and cell cycle distribution. Label-free quantitative proteomics and chromatin immunoprecipitation sequencing (ChIP-seq) were employed to identify top candidate downstream targets of ARID1A. ARID1A expression was decreased in high-risk GIST tissues. Furthermore, ARID1A knockdown in GIST cells promoted proliferation and metastasis both in vitro and in vivo, and led to reduced apoptosis and impaired cell cycle arrest. We further demonstrated that ARID1A suppresses GIST proliferation and metastasis by inhibiting MEMO1 expression and inactivating the ERK1/2 signaling pathway. Notably, this regulatory axis was observed in KIT-null GIST cells, indicating that the ARID1A-MEMO1 pathway may function independently of canonical KIT signaling. Thus, ARID1A inhibits malignant progression in GISTs, providing new insights into its role in the prevention and treatment of human GISTs and suggesting its potential as a biomarker of malignant progression in GISTs.

Metabolic reprogramming is a hallmark of tumor initiation and progression. Previous studies have focused mainly on glucose and lipid metabolism, with emphasis on the Warburg effect and de novo lipogenesis. Based on the shift in research paradigms, this review focuses on amino acid metabolism, which has long been overlooked, and systematically elaborates how tumors hijack amino acid pathways to construct an immunosuppressive and protumor microenvironment. We confirm that amino acid metabolism acts as a core driver of tumor proliferation, immune evasion and therapeutic resistance. This paper further discusses the intricate regulatory crosstalk between amino acid metabolism and convent ional antitumor therapies, clarifying the potential of metabolic-targeted strategies in overcoming drug resistance and improving clinical efficacy. Deviating from the traditional perception that amino acids merely serve as auxiliary substances for glucose and lipid metabolism, we summarize their vital roles in remodeling the immunosuppressive tumor microenvironment and provide theoretical support for the clinical integration of precise metabolic targeted therapy and existing antitumor regimens combined with cutting-edge technologies.

Background: Hyperuricemia and gout are linked to adverse outcomes and may influence frailty risk, but evidence on the impact of uric acid (UA)-lowering therapy on frailty among nephrology patients is limited. We evaluated the association of febuxostat and allopurinol use with incident and worsening frailty in a large nephrology patient cohort.

Methods: This retrospective cohort study included 19,389 adults attending nephrology clinics at a tertiary medical center in Taiwan between 2013 and 2021 with available UA and estimated glomerular filtration rate (eGFR) data. Exposure was the use of febuxostat, allopurinol, or both agents versus no UA-lowering therapy. We examined incident frailty and worsening frailty defined by the FRAIL scale after follow-up. Kaplan-Meier and Cox proportional hazards models were applied, adjusting for demographics, comorbidities, medications, baseline frailty, and laboratory data.

Results: Over a median follow-up of 3.0 years, 892 (4.6%) participants developed incident frailty and 5,253 (27.1%) had worsening frailty. After adjustment, febuxostat use was associated with higher probability of incident frailty (hazard ratio (HR) 1.22, 95% confidence interval (CI) 1.01-1.48), while allopurinol use was associated with lower probability (HR 0.65, 95% CI 0.46-0.93) compared to non-users. Both users had no alterations in incident frailty probability. Neither therapy was significantly associated with worsening frailty. Subgroup analyses showed modification effects from age and eGFR levels.

Conclusions: Among nephrology patients, UA-lowering therapy showed divergent associations with frailty probability: febuxostat use correlated with higher whereas allopurinol use correlated with lower incident frailty probability, with no effect on frailty progression. Choice of UA-lowering therapy may have implications for functional outcomes in this high-risk population.

Background: Early menarche is linked to adverse cardiometabolic outcomes, but its relationship with disease management remains unclear. We examined associations between menarcheal age and the prevalence and control of cardiometabolic diseases in Korean women.

Methods: In 25,227 women aged ≥19 years from the Korea National Health and Nutrition Examination Survey (KNHANES), 2014-2023, menarcheal age was categorized as early (<12 years), intermediate (12-15 years; reference), and late (≥16 years). Multivariable logistic regression assessed the prevalence and control of type 2 diabetes mellitus (T2DM), hypercholesterolemia, and hyper-low-density lipoprotein (LDL) cholesterolemia, stratified by menopausal status.

Results: Among premenopausal women, unadjusted comparisons favored the early-menarche group, reflecting age confounding; no significant association persisted after full adjustment for body mass index, lifestyle, and socioeconomic factors. Among postmenopausal women, late menarche was independently associated with lower odds of having hypercholesterolemia (OR = 0.809, 95% CI: 0.736-0.889; p < 0.001) and hyper-LDL cholesterolemia (OR = 0.815, 95% CI: 0.741-0.897; p < 0.001); no association with T2DM was observed. In contrast, among postmenopausal women who already had hyper-LDL cholesterolemia, those with late menarche were less likely to reach adequate LDL control than those with menarche at 12 to 15 years (OR = 0.814, 95% CI 0.693-0.956; p = 0.019). Although both odds ratios are below 1, they carry opposite clinical meaning, reflecting a lower prevalence of disease but poorer control once disease has developed.

Conclusions: The cardiometabolic effects of menarcheal age appear life-stage dependent, extending beyond prevalence to disease management. In postmenopausal women, late menarche was associated with lower odds of dyslipidemia yet, paradoxically, with poorer LDL control once disease had developed, indicating that a lower observed risk should not justify less vigilant management. These findings support integrating menarcheal age into cardiometabolic risk assessment.

Background: Dexmedetomidine is a highly selective α2-adrenergic receptor agonist that provides sedative and analgesic effects and may reduce opioid requirements without significant respiratory depression. However, evidence supporting its use in patients undergoing video-assisted thoracoscopic (VATS) lobectomy remains limited. This study aimed to evaluate the effects of perioperative dexmedetomidine on postoperative analgesic requirements and recovery outcomes in patients receiving combined epidural and general anesthesia.

Materials and methods: This prospective, randomized, double-blind study enrolled 68 patients undergoing elective VATS lobectomy. Patients were randomly assigned to the dexmedetomidine group (Group D) or the saline control group (Group S). All patients received standardized general anesthesia combined with thoracic epidural blockade. Group D received an intravenous loading dose of dexmedetomidine (1.0 μg/kg over 10 minutes), followed by a continuous infusion at 0.5 μg/kg/h until 1 hour after surgery, whereas Group S received a volume-matched saline infusion. The primary outcome was total patient-controlled epidural analgesia (PCEA) consumption. Secondary outcomes included visual analog scale (VAS) scores, Ramsay sedation scores, adverse events, and patient satisfaction assessed over 48 hours postoperatively.

Results: Sixty-one patients were included in the final analysis (Group D, n = 31; Group S, n = 30). Baseline demographic and intraoperative characteristics were comparable between groups. Intraoperative rocuronium requirements, cumulative patient-controlled epidural analgesia (PCEA) consumption from the intraoperative period to 48 hours postoperatively, and the number of rescue analgesic boluses administered in the post-anesthesia care unit were significantly lower in Group D than in Group S (p = 0.002, 0.001, and 0.013, respectively). Although overall postoperative pain scores were comparable between groups, VAS scores at 1 hour postoperatively were significantly lower in Group D (p = 0.038). Patient satisfaction scores were significantly higher in Group D (p = 0.005). Bradycardia 1 hour after surgery and hypotension 1 hour after one-lung ventilation occurred more frequently in Group D (p = 0.044 and 0.024, respectively), whereas the incidence of other adverse events was similar between groups.

Conclusions: Perioperative dexmedetomidine infusion reduced postoperative epidural analgesic requirements and improved early postoperative pain control and patient satisfaction in patients undergoing VATS lobectomy with combined epidural and general anesthesia. Despite an increased incidence of transient bradycardia and hypotension, dexmedetomidine was well tolerated and may be considered an effective opioid-sparing adjunct in this surgical population.

Background: Patients with chronic kidney disease (CKD) often experience cognitive decline. However, the associations between renal dysfunction, uremic toxins, and cerebrovascular changes remain unclear.

Aim: This study investigated the associations between renal function, uremic toxins, cerebrovascular imaging markers, and cognitive performance in patients with CKD plus early cognitive decline through integrated biochemical, neuropsychological, and neuroimaging assessments.

Design: An observational pilot study.

Setting: Outpatient clinic of the physical medicine and rehabilitation department at a tertiary hospital.

Population: Adult patients with stage 3-5 CKD who exhibited early cognitive decline and could complete CANTAB-based cognitive assessments.

Methods: This study included 12 patients with stage 3-5 CKD who were not undergoing hemodialysis and had early cognitive decline (Clinical Dementia Rating score: 0.5 or 1.0). Cognitive performance was assessed using the CANTAB. Serum levels of total indoxyl sulfate (IS) and total p-cresyl sulfate (pCS) were measured. Brain magnetic resonance imaging was performed to evaluate qualitative imaging markers potentially associated with cognitive impairment, such as arterial stenosis of the circle of Willis. Pearson correlations between the aforementioned biomarkers were explored.

Results: Both IS and pCS levels were negatively correlated with estimated glomerular filtration rate (IS: r = -0.301, p = 0.469; pCS: r = -0.461, p = 0.250). A higher estimated glomerular filtration rate was correlated with better spatial working memory strategy performance (r = 0.695, p = 0.012). However, no clear correlation was observed between cognitive performance and arterial stenosis severity.

Conclusion: This pilot study suggests that renal function is associated with selected cognitive domains in patients with CKD. The overall burden of qualitative MRI lesions was low in this cohort, although structural brain abnormalities were still observed. Integration of biochemical, neuropsychological, and brain imaging biomarkers may provide a comprehensive evaluation of cognitive function in these patients.

Clinical rehabilitation impact: Integrating multidomain cognitive assessments with uremic toxin profiling and noninvasive brain imaging may facilitate early identification of cognitive deficits in patients with CKD, thereby supporting individualized cognitive evaluation in rehabilitation practice.Trial Registration: NCT07272733.