Annals of medicine最新文献

Background: Emerging clinical evidence indicates that post-traumatic stress disorder (PTSD) may accelerate Alzheimer's disease progression, yet the molecular mechanisms linking these disorders remain poorly understood.

Methods: We conducted an integrative bioinformatics analysis combining blood cell profiles from PTSD and Alzheimer's disease cohorts to identify shared pathogenic pathways and therapeutic targets. Computational drug repositioning and experimental validation were used to pinpoint effective treatments.

Results: Our analysis revealed convergent dysregulation in neuroimmune and metabolic pathways, including compensatory upregulation of terpenoid biosynthesis and impaired JAK-STAT neuroprotective signaling. Cross-disorder network analysis identified CXCL8 as a central hub gene, prioritized through network pharmacology and machine learning. Mechanistic studies demonstrated that CXCL8 is dually regulated by stress-responsive transcriptional activators and neurodegeneration-associated microRNAs, positioning it as a key mediator of peripheral-central immune crosstalk. Immunoassays further linked CXCL8 to T cell recruitment (γδ T, CD8⁺ T), suggesting its role in sustaining neuroinflammation common to both diseases. Among potential therapeutics, nonsteroidal anti-inflammatory drugs emerged as modulators of CXCL8-driven pathology, with ibuprofen significantly suppressing neurodegeneration-associated CXCL8 overexpression.

Conclusions: Our findings highlight CXCL8-mediated neuroimmune dysregulation as a critical link between PTSD and Alzheimer's disease, supporting targeted anti-inflammatory strategies to mitigate stress-related dementia risk. This study advances a precision medicine framework for neurodegenerative comorbidities by integrating cross-disease molecular signatures.

Objective: To assess the survival benefit of synchronous systemic therapy plus thermal ablation (TA) in oligometastatic colorectal lung metastases (CRLM) and identify independent prognostic factors.

Background: Optimizing the integration of systemic therapy and TA for potentially curable CRLM remains a significant clinical challenge.

Methods: This study employed a retrospective cohort design, including 326 patients who underwent TA treatment at six tertiary medical centers from March 2014 to October 2022. Patients were categorized into synchronous therapy, upfront ablation, delayed ablation, and no systemic therapy groups based on the timing of systemic therapy relative to TA. Kaplan-Meier analysis and log-rank tests were used to assess survival outcomes.

Results: Synchronous systemic therapy yielded the longest median progression-free survival (PFS) (22.0 months) and overall survival (OS) (61.3 months) compared to delayed ablation (13.0 and 49.2 months, respectively) and no systemic therapy (11.9 and 29.3 months, respectively) (all p < 0.05). Synchronous systemic therapy was an independent protective factor for PFS [hazard ratio (HR) = 0.493] and OS (HR = 0.211). Independent risk factors for local tumor progression included tumor size ≥3 cm (HR = 1.75) and peridiaphragmatic location (HR = 1.48). For PFS, independent predictors included tumor numbers (p < 0.001), synchronous metastases (HR = 1.431), and extrapulmonary metastases (p = 0.001). OS was adversely influenced by tumor burden (p < 0.05), extrapulmonary metastases (p < 0.001), and mediastinal lymph node involvement (HR = 1.518).

Conclusions: Synchronous systemic therapy combined with TA significantly enhances PFS and OS in potentially curable oligometastatic CRLM patients.

Background: Osteoporosis significantly impacts global morbidity. Recent evidence suggests anaemia may contribute to osteoporosis risk. This systematic review and meta-analysis investigates this association.

Methods: PubMed, Scopus, EBSCO, and ScienceDirect were searched for papers. Studies with definition of anaemia and assessing osteoporosis outcomes were included. Meta-analysis utilized random-effects models (DerSimonian-Laird method), and study quality was assessed via Newcastle-Ottawa Scale (NOS). Analyses were performed using R Studio.

Result: Eighteen studies (861,540 participants) were analyzed. Anaemia significantly increased osteoporosis risk in univariate analysis (OR 1.62; 95% CI 1.33-1.98; p < 0.001), despite high heterogeneity (I² = 92.7%). The results remain significant in studies that reported multivariate analysis (OR 2.01; 95% CI 1.26-3.21; p = 0.004). Sensitivity analyses confirmed the robustness of our result.

Conclusion: Anaemia significantly associated with osteoporosis, emphasizing the need for targeted screening in anaemic individuals. Further studies should consider incorporating anaemia into osteoporosis and fracture prediction tools.

Objective: This study aimed to identify risk factors associated with the development of VTE in patients admitted to the intensive care unit (ICU).

Methods: A systematic literature search was conducted via PubMed, Embase, Web of Science, and Cochrane databases up to 25 April 2025, to identify studies examining the association between risk factors and the occurrence of venous thromboembolism (VTE) in ICU patients. Data were pooled using odds ratios (ORs) and 95% confidence intervals (CIs).

Results: A total of 2465 relevant studies were identified through the systematic search, of which 30 were included in the meta-analysis. The pooled data showed that the following were significant risk factors for venous thromboembolism (VTE) in ICU patients: central venous catheterization (OR = 2.67, 95% CI: 1.67-4.28; I² = 28%), invasive mechanical ventilation (OR = 2.08, 95% CI: 1.46-2.96; I² = 0%), advanced age (OR = 2.06, 95% CI: 1.28-3.31; I² = 86%), length of ICU stay (OR = 4.24, 95% CI: 1.43-12.57; I² = 98%), malignancy (OR = 2.30, 95% CI: 1.03-5.12; I² = 67%), elevated D-dimer levels (OR = 2.46, 95% CI: 1.37-4.40; I² = 34%), and a history of VTE (OR = 2.84, 95% CI: 1.45-5.55; I² = 51%). According to the GRADE assessment, the quality of evidence was rated as moderate for invasive mechanical ventilation, low for central venous catheterization and D-dimer levels, and very low for the remaining factors.

Conclusion: Invasive mechanical ventilation, central venous catheterization, and elevated D-dimer levels are associated with VTE risk, supported by relatively high-quality evidence. These findings may help identify ICU patients at higher risk of VTE, inform the development of risk assessment models for patient stratification, and ultimately contribute to improved prognosis through optimal screening and management strategies.

Background: This study investigates clinical characteristics influencing post-progression survival (PPS) in locally advanced esophageal squamous cell carcinoma (ESCC) after definitive chemoradiotherapy (dCRT), aiming to develop individualized follow-up strategies using conditional PPS.

Methods: The correlation between PPS and overall survival (OS) using Spearman correlation analysis. LASSO regression, Cox regression, and machine-learning methods were employed to identify prognostic factors, and a prediction model was constructed. The Shapley additive explanations (SHAP) method was used to interpret the model. Conditional PPS survival rates and recurrence risks were analyzed.

Results: This study enrolled 741 patients, with a median follow-up of 27.2 months. PPS was positively correlated with OS. Prognostic factors included: N stage, tumor length, chemotherapy cycles, platelet-to-albumin ratio, lymphocyte-to-monocyte ratio, age, body mass index, radiotherapy dose, and neutrophil to monocyte to lymphocyte ratio. Calibration curves, decision curves, and ROC curves demonstrated the model's stability and predictive performance. Subgroup analyses suggested shorter PPS in high-risk patients. After adjusting for other confounders, multi-model analyses continued to show a positive association between the risk score and unfavorable PPS. Conditional PPS analyses across different risk groups revealed that, with increasing survival time, conditional PPS extended correspondingly, and the relapse risk gradually decreased. Finally, individualized follow-up strategies were proposed, indicating intensified monitoring for high-risk patients.

Conclusion: This study fills the research gap in the influencing factors of PPS and personalized follow-up strategies for patients with locally advanced ESCC after dCRT, and provides important clinical evidence for promoting the transformation of post-recurrence management from 'experience-driven' to 'data-driven'.

Objective: Ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, has recently emerged as a promising therapeutic strategy for cervical cancer, particularly in tumors resistant to conventional radiotherapy and chemotherapy. This review aims to systematically summarize the current understanding of ferroptosis mechanisms in cervical cancer and its potential therapeutic implications.Methods: We comprehensively reviewed the literature focusing on key regulators of ferroptosis in cervical cancer, including system Xc- (SLC7A11), glutathione peroxidase 4 (GPX4), iron metabolism, and lipid peroxidation pathways. The interactions between ferroptotic processes and cervical cancer-specific cellular redox homeostasis and metabolic adaptations were analyzed. Additionally, the crosstalk between ferroptosis and oncogenic signaling pathways such as p53 and NRF2 was examined.Results: Accumulating preclinical evidence indicates that induction of ferroptosis sensitizes resistant cervical cancer cells to standard therapies by disrupting cellular redox balance and metabolic mechanisms. The intricate interplay between ferroptotic pathways and established tumorigenic signaling networks highlights the complexity of ferroptosis regulation in cervical cancer progression. Nonetheless, translational challenges remain, including the lack of robust ferroptosis-specific biomarkers for clinical application, potential off-target toxicity, and the need for optimized combination regimens.Conclusion: Future research should prioritize elucidating ferroptosis modulators within the tumor microenvironment, refining combinatorial therapeutic strategies, and developing targeted delivery systems. Integrating ferroptosis-based approaches with existing treatments holds significant potential to overcome therapeutic resistance and improve outcomes in advanced or recurrent cervical cancer. This review provides new insights and strategic directions for leveraging ferroptosis as a novel and actionable vulnerability in cervical cancer therapy.

Introduction: Endoscopic retrograde cholangiopancreatography (ERCP) is associated with significant discomfort and necessitates adequate sedation. This study aims to determine the effect of dexmedetomidine nasal spray adjunct to propofol sedation for patients undergoing ERCP procedures.

Patients and methods: This randomized, double-blind, placebo-controlled trial will be conducted at a tertiary teaching hospital in eastern China. Approximately 15 min before sedation, 160 adult patients will be randomly assigned (1:1) to either the dexmedetomidine group (dexmedetomidine nasal spray; n = 80) or the control group (normal saline nasal spray; n = 80). Sedation will be achieved with a target-controlled infusion of propofol, titrated to Modified Observer's Assessment of Alertness/Sedation scores of 1 and 2. The primary endpoint is the total propofol consumption during sedation. Secondary endpoints include the composite incidence of hypotension and hypoxemia during the procedures and recovery; and fatigue scores 15 min after emergence from sedation. An independent Data and Safety Monitoring Committee will conduct an ongoing review of study implementation.

Discussion: We anticipate that preoperative dexmedetomidine nasal spray will decrease total propofol requirements, reduce sedation-related adverse events, and enhance recovery for patients undergoing ERCP.

Trial registration: Chinese Clinical Trial Registry (ChiCTR2400093656) on December 10, 2024.

Background: Rapid autonomic recovery after physical stress is a hallmark of cardiovascular health. While both yoga and conventional exercise modulate autonomic function, direct comparisons of their effect on post-exercise recovery are scarce. This study compared autonomic recovery in yoga practitioners versus those in aerobic or resistance training.

Methods: We conducted a cross-sectional study of 51 healthy adults (18-35 years) in three long-term training groups: Yoga (n = 17), Aerobic (n = 17), and Resistance (n = 17). Participants performed a 5-minute submaximal Harvard step test. Heart rate variability (HRV) was analyzed from electrocardiograms recorded at baseline and during a 10-minute post-exercise recovery.

Results: After adjusting for baseline differences, the Yoga group showed a more efficient autonomic recovery profile. ANCOVA revealed a significant group effect on vagal reactivation, as measured by High-Frequency (HF) power (p = 0.001). Post-hoc tests confirmed that the Yoga group's recovery was significantly greater than that of the Aerobic and Resistance groups. Similar significant effects favouring Yoga were found for pNN50, SDNN, LF power, and total power (all p < 0.05). No significant group differences were observed for pulse rate, blood pressure, or RMSSD recovery.

Conclusion: Regular yoga practice is associated with more efficient parasympathetic reactivation after physical exertion. This suggests yoga's integrative nature is associated with unique advantages for autonomic strength compared to conventional aerobic and strength training.

Background and aims: Systemic inflammation is closely linked to the development and progression of various cancers, as well as poorer patient outcomes. The role of the c-reactive protein to albumin ratio (CAR) as a predictor of poor prognosis in renal cell carcinoma (RCC) remains insufficiently recognized.

Methods: A literature search was conducted in major English-language databases, including PubMed, EMBASE, and the Cochrane Library, with the search updated to 25 June 2025. Both the odds ratio (OR) and diagnostic odds ratio (DOR) were employed to evaluate the prognostic performance of CAR.

Results: This meta-analysis ultimately included 10 studies with a total of 2478 patients with RCC. The results showed that high baseline CAR was significantly associated with poor prognosis or recurrence of RCC. The sensitivity of 0.73 (95% confidence interval [CI]. 0.69-0.77); specificity of 0.69 (95% CI: 0.64-0.74) and DOR of 6.0 (95% CI: 5.0-8.0) were pooled estimated from patient-based analyses. Subsequently, the combined positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were calculated with the results of 2.4 (95% CI: 2.0-2.8) and 0.39 (95% CI: 0.33-0.46), respectively. Furthermore, the area under the curve (AUC) of the summary receiver operating characteristic (SROC), which reflects prognostic accuracy, was 0.77 (95% CI: 0.73-0.81). In addition, subgroup analysis indicated that elevated CAR was more predictive of overall survival (OS) in RCC patients in China.

Conclusions: Our findings indicate that an elevated CAR serves as a strong predictor of poor prognosis or recurrence in patients with RCC.

Background: Autonomic dysfunction, including orthostatic hypotension and postural tachycardia syndrome, has emerged as a COVID-19 complication. This nationwide propensity score-matched cohort study investigated COVID-19's impact on subsequent prescriptions of autonomic dysfunction in Japan.

Patients and methods: Using a claims database covering 16 million residents identified between 2020 and 2022, propensity-score matching (PSM) created comparable groups of COVID-19 patients and controls. PSM used age, sex, calendar month, comorbidities, and baseline medications, with nearest-neighbor 1:1 with replacement. The primary composite outcome was the first outpatient prescription of midodrine, fludrocortisone, amezinium methylsulfate, and droxidopa. Cox proportional hazards models yielded hazard ratios (HRs) with 95% confidence intervals (CIs). Effect modifications were examined by subgroups.

Results: Among 3,074,329 matched pairs, over a median follow-up of 8 months, 13011 composite outcome were observed, and COVID-19 infection was associated with a 36% relative increase in prescriptions (HR 1.36, 95%CI 1.32-1.41). The risk persisted beyond one year, with the strongest association observed for fludrocortisone (576 events, HR 1.71, 95%CI 1.44-2.02), although the frequency was the highest in midodrine prescription (7009 events, HR 1.28, 95%CI 1.22-1.34). Subgroup analysis revealed higher risks among older individuals, males, those with myocardial infarction, heart failure, and antihypertensive medications.

Conclusions: COVID-19 infection is significantly associated with increased initiation of pharmacotherapy for autonomic dysfunction, with sustained risk beyond one year. These findings highlight the to manage autonomic dysfunction among COVID-19 survivors and informing clinical care and public health planning.