International Journal of Medical Sciences最新文献

This review examines the evidence linking air pollution, particularly fine particulate matter (PM2.5), to aortic diseases such as atherosclerosis, aneurysms, and dissections. Air pollution is a significant environmental risk factor for cardiovascular disease, and understanding its impact on the aorta is crucial for developing prevention strategies. We performed a comprehensive literature search of PubMed for articles published between December 2007 and May 2024, including in vivo, in vitro, and clinical studies that investigate the effects of air pollution on aortic pathophysiology. Findings indicate that exposure to PM2.5 and diesel exhaust particles accelerates aortic atherosclerosis, aneurysm formation, and dissection through mechanisms involving oxidative stress, inflammation, endothelial dysfunction, and vascular remodelling, with heightened effects in genetically predisposed models and high-fat diets. In vitro studies reveal that particles can cause cytotoxicity in human aortic endothelial cells, characterized by reduced nitric oxide production and cellular damage. Clinical data are mixed but suggest associations between air pollution and increased aortic calcification, arterial stiffness, and altered hemodynamics. Overall, air pollution influences the development and progression of aortic diseases via multiple biological pathways, emphasizing the need for further research to define dose-response relationships, identify molecular targets, and implement environmental interventions to reduce disease burden and protect public health.

Background: Carpal tunnel syndrome (CTS) is a common entrapment neuropathy involving chronic inflammation, while glaucoma is an optic neuropathy linked to neuroinflammation and vascular insufficiency. Shared pathogenic mechanisms have been hypothesized, but large-scale epidemiologic evidence is lacking. This study aims to evaluate whether CTS patients present an elevated risk of glaucoma compared to CTS-free individuals. Materials and Methods: We conducted a retrospective cohort study using the TriNetX global research network. Adults diagnosed with CTS were matched 1:1 with CTS-free controls based on demographics, comorbidities, and healthcare utilization. The primary outcome was new-onset glaucoma, with subtypes assessed separately. Cox proportional hazard models were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). Sensitivity analyses included alternative matching algorithms, washout periods, and comparisons with autoimmune musculoskeletal diseases. Results: After matching (n = 733,997 per group), CTS was associated with an increased risk of glaucoma (HR = 1.57, 95% CI: 1.52-1.62). Risks were elevated across glaucoma subtypes, including open-angle glaucoma (HR = 1.55, 95% CI: 1.44-1.66) and angle-closure glaucoma (HR = 1.67, 95% CI: 1.38-2.02). Sensitivity analyses confirmed the robustness of the association across multiple models. When compared to patients with autoimmune musculoskeletal diseases, CTS patients had a higher risk of glaucoma than those with rheumatoid arthritis (HR = 1.73, 95% CI: 1.60-1.87) or ankylosing spondylitis (HR = 1.36, 95% CI: 1.20-1.53). Conclusion: Carpal tunnel syndrome is associated with a significantly increased risk of glaucoma. These findings support the involvement of shared inflammatory or vascular mechanisms and highlight the growing concern about ocular comorbidities in patients with CTS.

Background: Lower extremity lymphedema is a chronic surgical disease marked by lymphatic obstruction, fibrosis, and recurrent infection. Conservative therapy is often inadequate in advanced cases. Vascularized lymph node transfer (VLNT) restores drainage through lymphangiogenesis and node regeneration. The omentum, rich in lymphoid tissue and VEGF-C secretion, is an underutilized donor site. This study evaluated the safety, efficacy, and mechanistic outcomes of laparoscopic omental lymph node flap transfer. Methods: This retrospective case series evaluated, twelve patients (14 limbs) with advanced lower extremity lymphedema underwent laparoscopic omental VLNT. Outcomes included limb circumference reduction, resolution of lymphangitis, lymphoscintigraphic improvement, and donor-site morbidity. Lymphoscintigraphy at 12 months assessed functional restoration and tracer uptake as surrogates of lymphangiogenesis. Results: At a mean follow-up of 27 (12-43) months, the mean circumference reduction was 29%, greatest in distal segments. All recurrent lymphangitis resolved, and chronic wounds healed within 3 months. Lymphoscintigraphy demonstrated enhanced drainage, reduced dermal backflow, and increased tracer uptake within transferred flaps, suggesting functional integration. Flap survival was 93%, with no gastrointestinal complications or donor-site hernia. Patients reported improved skin texture, reduced heaviness, and greater walking tolerance. Conclusions: Laparoscopic omental VLNT is a safe and effective option for refractory lower extremity lymphedema. Clinical improvements were supported by lymphoscintigraphic consistent with lymphangiogenesis and lymphatic restoration. This minimally invasive approach represents an important advancement in physiologic lymphedema surgery.

Background: Acetaminophen is widely used in intensive care units, yet its impact on mortality among critically ill patients with primary lung cancer remains unclear. Given the high disease burden and potential immunomodulatory effects of acetaminophen, robust evidence is needed to clarify its prognostic relevance in this population. Methods: We conducted a retrospective cohort study using the MIMIC-IV v2.2 database, including 1,127 critically ill patients with primary lung cancer. Baseline variables comprised demographics, comorbidities, illness severity scores (SOFA, APSIII, SAPSII, OASIS), and laboratory parameters. To minimize confounding, propensity score matching was applied. Results: A total of 1,127 critically ill patients with primary lung cancer were included, of whom 403 received acetaminophen. The 28-day mortality rate was 22.0% in the acetaminophen group compared to 37.5% in the non-acetaminophen group. After adjusting for baseline differences using inverse probability of treatment weighting (IPTW), acetaminophen exposure was associated with a significantly lower risk of 28-day mortality (HR=0.75, 95% CI: 0.60-0.93, p=0.015). In addition to 28-day mortality, acetaminophen use was consistently associated with reduced risks of ICU mortality, in-hospital mortality, 30-day mortality, 90-day mortality, and 365-day mortality. Subgroup analyses identified patients aged ≥65 years and those with a SOFA score ≥3 as particularly noteworthy subgroups. Conclusion: Acetaminophen use was associated with significantly reduced short- and long-term mortality in critically ill patients with primary lung cancer. These findings suggest a potential survival benefit beyond its conventional symptomatic use and underscore the need for prospective studies to validate its therapeutic role in this high-risk population.

Despite significant advancements in cardiopulmonary resuscitation (CPR) techniques, the global burden of sudden cardiac death remains high, with post-CPR survival rates persistently below 8%. Hypoxic-ischemic brain injury (HIBI) is the predominant cause of mortality, accounting for 68% of fatalities following resuscitation. Hyperbaric oxygen (HBO) therapy, which enhances oxygen dissolution in plasma, has demonstrated efficacy in focal cerebral ischemia conditions such as stroke. However, its potential in addressing global cerebral ischemia following CPR-a condition pathophysiologically distinct due to the absence of a salvageable ischemic penumbra and characterized by pan-cerebral energy failure-remains insufficiently explored. This review synthesizes emerging evidence from both focal and global ischemia models, highlighting the role of HBO in modulating key injury mechanisms common to both conditions, including oxidative stress, neuroinflammation, and ferroptosis. By integrating findings on HBO-induced upregulation of endogenous antioxidants, suppression of pro-inflammatory cytokines, and stabilization of mitochondrial function, we propose a combined therapeutic strategy that incorporates HBO with advanced CPR techniques and adjunctive therapies to mitigate HIBI.

Purpose: Liver transplantation (LT) is a risky but life-saving treatment for end-stage liver disease. Dynamic changes in systemic inflammation can inform disease progression and postoperative recovery. This retrospective study investigated the prognostic impact of these chronological changes in patients undergoing LT. Methods: Inflammatory statuses were assessed using the neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) measured preoperatively (within 7 days before surgery) and postoperatively (between days 21 and 90, before any re-exploration). Their predictive performances for three-year postoperative mortality were evaluated. Using the best-performing index, the patients were stratified into normal (persistently low), elevated (low-to-high), normalized (high-to-low), and persistent (persistently high) groups, and associations with mortality were analyzed. Results: A total of 377 patients were included. Among inflammatory indices, the NLR had the highest mortality prediction accuracy. Patients grouped by pre- and postoperative NLR cutoffs (4.2 and 24.0) showed significant mortality differences, with stepwise risk increases from normal to normalized and persistent groups. The NLR-based group was an independent mortality predictor. Compared with the normal group, the normalized and persistent groups had higher mortality, prolonged ventilation, and longer intensive care unit (ICU) and hospital stays. Conclusion: Dynamic changes in systemic inflammation, reflected by pre- and postoperative NLR, were strongly associated with long-term mortality after LT. The NLR is a reliable, accessible inflammatory marker. Elevated preoperative NLR was associated with poor outcomes, with persistent postoperative elevation indicating a worse prognosis than normalization. NLR trajectory may help identify high-risk LT patients and guide postoperative care.

Background: Pancreatic cancer (PaC) is characterized by poor prognosis. This study aimed to identify mitophagy-related clusters and develop a prognostic model for PaC. Methods: Differentially expressed genes (DEGs) between PaC and normal tissues were identified from the TCGA and GTEx cohorts. Mitophagy-related genes (MRGs) were sourced from Reactome, GO, and KEGG databases. The intersection of DEGs and MRGs identified differentially expressed MRGs (DeMRGs). Consensus clustering identified PaC subtypes based on DeMRG expression. Univariate Cox analysis was used to find prognosis-related genes, and LASSO regression analysis was employed to develop the prognostic model. A nomogram was constructed to predict survival probabilities. Results: A total of 7,240 DEGs were identified between PaC tissues and normal controls. From these, 12 DeMRGs were identified, and consensus clustering revealed three distinct molecular clusters. A prognostic model based on six significant genes (PAPPA, NBPF12, CXCL11, CKLF-CMTM1, CCDC6, AHNAK) was developed using LASSO regression analysis. This model demonstrated good predictive performance for overall survival in the TCGA cohort, with AUC values of 0.78, 0.74, and 0.82 for 1-, 2-, and 3-year survival in the training set, and 0.73, 0.82, and 0.73 in the validation set. External validation in independent GEO cohorts demonstrated moderate predictive performance. The nomogram demonstrated good calibration and accuracy in predicting survival. Significant correlations were found between the risk model and immune cell infiltration. High-risk patients showed higher sensitivity to dasatinib and staurosporine. Conclusions: The study identified mitophagy-related molecular clusters and developed a prognostic model for PaC. This model may help predict overall survival and guide personalized treatment strategies for PaC patients.

Background: Pre-existing atrial fibrillation (AF) and postoperative new-onset AF (NOAF) are independent perioperative risk factors associated with increased short-term mortality and adverse events. This study aimed to develop and validate an artificial intelligence (AI) model capable of detecting hidden AF, including both pre-existing AF and NOAF, from sinus rhythm electrocardiograms, to improve perioperative risks assessment. Methods: We trained and validated an AI model to detect hidden AF. Subsequent analysis confirmed the prognostic relevance of both pre-existing AF and NOAF in patients receiving non-cardiac surgery. The AI model was applied to patients without known AF to evaluate its predictive capability for NOAF and to stratify short-term clinical outcomes. Results: The AI model demonstrated an area under the receiver operating characteristic curve of 0.87 during the development phase for predicting AF. In an independent validation cohort, pre-existing AF and postoperative NOAF were significantly correlated with increased 30-day all-cause mortality. Patients without pre-existing AF who were classified as high-risk by the AI model had substantially higher 30-day all-cause mortality than their low-risk counterparts (HR 17.33, 95% CI 5.29-56.75). Furthermore, the model scores surpassed conventional clinical risk scores in predicting NOAF and 30-day all-cause mortality. Conclusions: This AI-based approach facilitated the accurate identification of patients with elevated perioperative AF-related risk. It will facilitate focused interventions that may enhance clinical outcomes.

Pancreatic adenocarcinoma (PAAD), the predominant form of pancreatic cancer, is highly aggressive and refractory to current therapies. The Amphoterin-Induced Gene and ORF (AMIGO) family encodes three structurally related type I transmembrane proteins (AMIGO1-3) containing leucine-rich repeat and immunoglobulin-like domains, which mediate cell adhesion and signaling. Although AMIGO proteins have been implicated in neural development and tumor progression, their functional relevance in PAAD remains unclear. Here we identify AMIGO2 as a key driver of PAAD progression through integrated transcriptomic, proteomic, and functional analyses. Multi-cohort datasets (ONCOMINE, TCGA) and immunohistochemistry revealed marked AMIGO2 overexpression in PAAD tissues, with recurrent genetic alterations (~11%) and strong association with poor relapse-free and overall survival. Functional enrichment of AMIGO2-correlated genes indicated activation of focal adhesion and PI3K/AKT signaling. Consistently, inhibition of AMIGO2 expression in pancreatic cancer cells reduced migration and invasion while restoring E-cadherin expression, indicating inhibition of epithelial mesenchymal transition. Protein profiling from the Human Protein Atlas further confirmed elevated AMIGO2 expression in tumors. Together, these findings demonstrate that AMIGO2 promotes PAAD aggressiveness by enhancing adhesion- and EMT-associated pathways, establishing it as a potential prognostic biomarker and therapeutic target in pancreatic cancer.

Background: Insufficient liver regenerative capacity poses life-threatening risks to patients following partial hepatectomy (PHx), and existing clinical treatments provide limited options for enhancing regeneration. Lymphatic vasculature plays essential roles in the immune response through the uptake and transport of pathogens, antigens, inflammatory mediators, and antigen-presenting cells. Recent research has shown that lymphangiogenesis may contribute to both heart and bone regeneration. However, the role and underlying mechanisms of intrahepatic lymphangiogenesis in liver regeneration remain unclear. Methods: Single-cell RNA sequencing was employed to identify dynamic changes in lymphatic endothelial cells (LyECs) in liver tissues following 70% PHx. A mouse model of liver regeneration was utilized to assess the contribution of intrahepatic lymphangiogenesis to the regenerative process after 70% PHx. Additionally, an adeno-associated virus overexpressing vascular endothelial growth factor-C (AAV-VEGF-C) was used to confirm the role of intrahepatic lymphangiogenesis in liver regeneration. qRT-PCR, western blotting and immunofluorescence staining were performed to investigate the potential underlying mechanisms. Furthermore, a neutralizing rat anti-murine anti-IL-6 antibody (anti-IL-6) was used to verify signaling pathway. Results: Single-cell RNA sequencing analysis revealed dynamic changes of LyECs in liver tissues following 70% PHx. Consistent with these findings, the number and area of intrahepatic lymphatic vessels (LVs) around the portal tract significantly decreased on postoperative day 3 (POD3) in the mouse model of 70% PHx compared to the sham group, but the number and area recovered by POD7. Additionally, vascular endothelial growth factor-C(VEGF-C), a pro-lymphangiogenic growth factor, was found to increase in the liver of the 70% PHx mouse model. Stimulation of lymphangiogenesis with AAV-VEGF-C significantly accelerated liver regeneration and repair. Mechanistically, intrahepatic lymphangiogenesis might accelerate liver regeneration by the activation of the IL-6/STAT3 pathway. Blocking IL-6 reversed lymphangiogenesis-accelerated liver regeneration. Conclusions: Intrahepatic lymphangiogenesis may contribute to early liver regeneration after PHx, with partial dependence on IL-6/STAT3 signaling. These findings support further investigation of lymphatic-modulating approaches as potential adjuncts to enhance postoperative recovery after PHx, particularly in selected contexts.