American journal of translational research最新文献

Objectives: Pre-eclampsia (PE) is a leading cause of maternal and fetal mortality, with inflammatory dysregulation implicated in its pathogenesis. This Mendelian randomization (MR) study aimed to investigate the causal effects of 91 inflammatory cytokines on PE and to identify potential mediating metabolites.

Methods: We conducted a two-sample MR analysis using genome-wide association study data from European-ancestry populations: including 91 inflammatory cytokines (14,824 participants), 1,400 plasma metabolites (8,299 participants), and PE (2,355 cases; 264,887 controls). Instrumental variables were selected at P < 1 × 10^-5. Causal estimates were assessed using inverse-variance weighted regression, with additional sensitivity analyses to evaluate MR assumptions. Mediation analysis was subsequently performed to identify relevant metabolite pathways.

Results: We identified two novel risk factors and two protective factors for PE: genetically proxied elevations in fibroblast growth factor 5 (FGF-5) and Matrix metalloproteinase-1 (MMP-1) increased PE risk, whereas interleukin-10 (IL-10) and interleukin-20 (IL-20) were protective. Importantly, this is the first MR study to identify N-acetyl-L-alanine (ALA) as a significant mediator of cytokine effects in PE. ALA mediated 5.56% of the effect of FGF-5, revealing a pathway whereby elevated FGF-5 reduces ALA levels and consequently increases PE risk.

Conclusions: This study establishes FGF-5 and MMP-1 as novel causal risk factors for PE, while IL-10 and IL-20 exert protective effects. The identification of ALA as a partial mediator of FGF-5 uncovers a new metabolic-inflammatory pathway in the pathogenesis of PE. These findings highlight potential biomarkers and therapeutic targets for the prevention and treatment of PE.

Objectives: To investigate the synergistic anti-tumor effects and underlying mechanisms of combining cytokine-induced killer (CIK) cell therapy with programmed death 1 (PD-1) blockade in the treatment of nasopharyngeal carcinoma (NPC).

Methods: CIK cells were generated from peripheral blood mononuclear cells (PBMCs) of healthy donors. The combinatorial effects were assessed in vitro by co-culturing CIK cells with HK-1 NPC cells to assess cytotoxicity, apoptosis-related gene expression, cytokine secretion, and activation of the mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. In vivo efficacy was evaluated in a NOD scid gamma (NSG) mouse xenograft model (n=6/group).

Results: In vitro, PD-1 blockade dose-dependently enhanced CIK cell-mediated cytotoxicity, apoptosis, and secretion of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 (IL-2), concomitant with MEK/ERK pathway activation. In vivo, combination therapy significantly inhibited tumor growth compared with either monotherapy. This was associated with increased infiltration of cluster of differentiation (CD)3⁺, CD4⁺, CD8⁺, and CD56⁺ immune cells, enhanced tumor apoptosis (TUNEL+), reduced proliferation (Ki67), and alleviated oxidative stress within the tumor microenvironment.

Conclusions: Combined CIK cell therapy and PD-1 blockade demonstrated significant synergistic anti-tumor activity against NPC by enhancing cytotoxicity, activating key signaling pathways, and remodeling the tumor immune microenvironment. This strategy represents a promising therapeutic approach for NPC.

Objective: To investigate the correlation between intraorbital tissue structures and diplopia in patients with thyroid-associated ophthalmopathy (TAO) using magnetic resonance imaging (MRI) technology.

Methods: A retrospective analysis was conducted on 228 patients with TAO who were diagnosed and treated at the Affiliated Hospital of Yunnan University between March 2021 and June 2024. Patients were divided into a diplopia group (n=105) and a non-diplopia group (n=123) based on the presence or absence of diplopia.

Results: Logistic regression analysis showed that a higher thyroid-stimulating hormone receptor antibody (TRAb) level was an independent protective factor against diplopia in TAO, whereas increased thickness of the inferior rectus (IR), medial rectus (MR), and lateral rectus (LR), as well as greater extraocular muscle volume (EMV), were independent risk factors (all P<0.05). The areas under the ROC curve (AUCs) for TRAb, IR, EMV, MR, and LR in predicting diplopia were 0.909, 0.863, 0.834, 0.732, and 0.637, respectively. The combined model achieved an AUC of 0.986, indicating excellent predictive performance. Moreover, the duration of diplopia was positively correlated with IR, MR, and LR thickness.

Conclusion: MRI enables quantitative evaluation of intraorbital structural alterations in TAO patients. When integrated with clinical characteristics, it provides valuable guidance for the early identification and intervention of diplopia.

Objectives: Diquat (DQ) induces severe cardiotoxicity through oxidative stress, yet no specific antidote is currently available. Klotho, a known agonist of nuclear factor erythroid 2-related factor 2 (Nrf2), exerts antioxidative effects in various diseases. However, its role in DQ-induced myocardial injury remains undefined.

Methods: Acute myocardial injury was induced in rats by intragastric DQ administration, followed by treatment with recombinant Klotho protein. Myocardial histopathology, oxidative stress markers, and components of the Nrf2/antioxidant response elements (ARE) pathway - including Nrf2, heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase 1 (NQO1) - were evaluated. Additionally, DQ-exposed H9c2 cardiomyocytes were treated with Klotho or the Nrf2 inhibitor ML385. cell viability, apoptosis, oxidative stress markers, and Nrf2 pathway protein expression were evaluated.

Results: DQ administration induced significant oxidative stress and upregulated mRNA levels (2-3-fold; all P<0.0001) and protein expression (1.3-1.4-fold; P=0.0018, P=0.0039, P=0.0030) of Nrf2, HO-1, NQO1 in rat myocardial tissues. Klotho treatment effectively preserved H9c2 cell viability (by 60%; P<0.0001), reduced apoptosis (by 43%; P<0.0001), and alleviated oxidative stress (all P<0.0001). Klotho also enhanced Nrf2, HO-1, and NQO1 protein expression (2.5-3-fold; all P<0.0001). ML385 abrogated the protective effects of Klotho against DQ-induced oxidative stress (all P<0.0001) and apoptosis (all P<0.0001) in H9c2 cells. In vivo, recombinant Klotho administration attenuated myocardial histopathologic damage, normalized oxidative stress markers (all P<0.0001), and increased Nrf2, HO-1, NQO1 protein levels (1.8-2-fold; all P<0.0001).

Conclusion: Klotho mitigates DQ-induced myocardial injury in rats by activating Nrf2/ARE signaling pathway and suppressing oxidative stress.

Objective: To compare the performance of a robotic (da Vinci Xi-based) scope holder with manual holding during laparoscopic colorectal cancer (CRC) surgery.

Methods: A total of 170 CRC cases were retrospectively assigned to two equal groups: an investigation group (da Vinci Xi-assisted procedures) and a reference group (human camera assistant). Surgical and recovery outcomes were analyzed, including pain intensity, stress levels, and gastrointestinal and humoral immune functions. Additionally, the safety of the procedures and surgeons' subjective experiences were evaluated.

Results: The investigation group showed significant improvements, including reduced blood loss, shorter surgical duration, earlier drain removal and discharge, lower costs, and less post-operative pain (24, 48, and 72 hours post-surgery). This group also exhibited lower stress levels, fewer complications, and better recovery in terms of gastrointestinal and humoral immunity (all P<0.05). Surgeons in the investigation group reported higher scores for procedural vigor, operational efficiency, and comfort (P<0.05).

Conclusion: The robotic system offers clinical advantages in laparoscopic CRC procedures.

Objectives: Colorectal cancer (CRC) has one of the highest incidence and mortality rates among cancers, particularly concerning the rates of diagnosis. Serum exosomes (Exos) are crucial mediators for the intercellular transmission of genetic information. These vesicles contain various tRNA-derived fragments (tRFs) that play a role in the noncoding regulation of tumor genes. Consequently, they are anticipated to become valuable non-invasive diagnostic and predictive biomarkers for CRC.

Methods: At the Affiliated Taian City Central Hospital of Qingdao University, we isolated and extracted serum Exos from 201 healthy donors and 205 patients with CRC. To measure Exo physical morphology, we utilized qNano, transmission electron microscopy, and a particle size analyzer. Western blotting was conducted to confirm the expression of surface and nuclear proteins in the Exos. Gene chips were employed to screen for differentially expressed tRF RNAs. The quantitative PCR technology was deployed to ascertain 5'Leader-ArgTCG and 3'tRF-SerGCT differential expression. CRC diagnostic efficiency was assessed utilizing the area under the curve.

Results: We compared 5'Leader-ArgTCG and 3'tRF-SerGCT expression in 205 patients with CRC and 201 healthy donors. Among them, 5'Leader-ArgTCG was significantly downregulated, while 3'tRF-SerGCT was significantly upregulated. The diagnostic efficiency of predicting 5'Leader-ArgTCG and 3'tRF-SerGCT in serum Exos using survival curves was 0.659 and 0.659, respectively. Meanwhile, the diagnostic efficiency of combining the two tumor markers was 0.954.

Conclusion: Serum Exos 5'Leader-ArgTCG and 3'tRF-SerGCT were differentially expressed in patients with CRC. Combining these two tumor markers may serve as a predictive indicator for the non-invasive diagnosis of CRC, demonstrating notable statistical significance.

Objective: To evaluate the therapeutic effect of the waist-rubbing method on lumbar disc herniation (LDH) and explore its immunoregulatory mechanisms.

Methods: Forty Sprague-Dawley rats were randomly divided into three groups: control, model, and treatment groups. The control group did not undergo modeling, while LDH models were established in the other two groups. Behavioral tests were conducted on all rats at designated time points, and neurological function scores were compared among groups. After 15 days of corresponding interventions, peripheral blood samples were collected for flow cytometric analysis of T-cell subsets. Serum levels of corticosterone (CORT), glucocorticoid receptor α (GR_α), interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-17, and transforming growth factor-β (TGF-β) were detected using enzyme-linked immunosorbent assay.

Results: Compared with the control group, the model group showed significantly increased Th1/Th2 and Th17/Treg ratios, elevated serum levels of IFN-γ and IL-17, and decreased CORT, GR_α, IL-4 and TGF-β levels (all P<0.05). Compared with the model group, the treatment group exhibited significantly reduced ratios of IFN-γ+CD8+ T cells, IL-17+CD8+ T cells, FOXP3+CD4+ T cells and IL-4+CD4+ T cells, accompanied by increased serum CORT, GR_α, IL-4, and TGF-β levels and decreased IFN-γ and IL-17 levels (P<0.05).

Conclusion: The waist-rubbing method may alleviate autoimmune disorders in LDH by enhancing hypothalamic-pituitary-adrenal (HPA) axis activity and restoring Th1/Th2 and Th17/Treg balance, providing mechanistic support for the traditional concept of "tonifying the kidney to relieve pain".

Objectives: To investigate the clinical characteristics of patients with post-traumatic facial hypertrophic scars treated with fractional carbon dioxide (CO₂) laser therapy and to identify factors associated with the duration of postoperative erythema.

Methods: This retrospective study included 106 patients who underwent fractional CO₂ laser therapy for post-traumatic facial hypertrophic scars at Huzhou Maternity & Child Health Care Hospital between January and April 2025. Demographic data, scar characteristics (area, location, Vancouver Scar Scale [VSS] score), laser parameters, adverse reactions, and erythema duration were collected. Patients were categorized into short-duration and long-duration erythema groups using a 14-day cutoff. Clinical variables were compared between groups, and those with P < 0.05 were further analyzed using Spearman correlation.

Results: Among 106 included patients, most were children or adolescents. The median erythema duration was 11 days, and 25 patients experienced erythema lasting longer than 14 days. Patients in the long-duration group had significantly higher age, scar area, VSS score, and laser energy compared with those in the short-duration group (P < 0.05). All four variables showed a positive correlation with erythema duration (P < 0.0001). Analysis of adverse events revealed a significant difference in Fitzpatrick skin type distribution between patients with and without edema (P = 0.021).

Conclusions: The duration of postoperative erythema is strongly associated with patient age, scar severity, and laser treatment parameters. Preoperative evaluation should account for these factors to guide individualized treatment planning and postoperative care, thereby minimizing the risk of prolonged erythema.

Objectives: To develop and validate a hybrid deep learning model to enhance diagnostic and predictive accuracy of Alzheimer's disease (AD) using readily available clinical data.

Methods: A triple-architecture joint model was constructed, integrating a Kernel Extreme Learning Machine (KELM), a Long Short-Term Memory (LSTM) network, and a Transformer. This framework was designed to capture nonlinear associations, temporal dynamics, and global feature dependencies. The model was trained and validated on 2,149 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database and externally tested on an independent cohort of 1,012 subjects.

Results: In internal validation, the model achieved state-of-the-art performance with 95.42% accuracy, 95.63% recall, and an area under the curve (AUC) of 0.981. It also demonstrated strong generalizability in the external cohort, achieving 93.81% accuracy and an AUC of 97.25%. In a longitudinal sub-analysis, the model accurately predicted the 3-year conversion from mild cognitive impairment to AD with 92.78% accuracy. Ablation analyses confirmed the essential contribution of each model component.

Conclusions: The proposed KELM-LSTM-Transformer model provides a powerful and robust framework for AD prediction. Its high accuracy and strong generalizability suggest potential as an effective and accessible tool for early risk stratification, supporting timely clinical interventions.

Objective: To investigate the factors influencing low intake dehydration in patients with malignant tumors and to construct a nomogram model for predicting its risk.

Methods: A total of 383 patients with malignant tumors were enrolled in this study. Based on the presence of low intake dehydration at admission, patients were classified into a dehydration group (119 patients) and a non-dehydration group (264 patients). Multiple logistic regression analysis was used to identify factors associated with low intake dehydration. A nomogram model was subsequently constructed, and its predictive performance was validated.

Results: Significant differences were observed between the dehydration and non-dehydration groups in age (χ² = 6.988, P = 0.008), serum albumin (t = 3.158, P = 0.002), tumor duration (t = 4.257, P < 0.001), swallowing disorders (χ² = 8.753, P = 0.003), Cancer Patient Appetite Questionnaire (CASQ) score (t = 3.373, P = 0.001), and Barthel Index (BI) score (t = 2.768, P = 0.006). Logistic regression analysis revealed that age ≥ 60 years, serum albumin level, tumor duration, dysphagia, CASQ score, and BI score were significant factors associated with low intake dehydration in cancer patients. The constructed nomogram model showed no overfitting (P > 0.05 in the goodness-of-fit test), with an area under the ROC curve of 0.861. Decision curve analysis confirmed the model's practical value. Ten-fold cross-validation demonstrated the robustness of the model.

Conclusions: The risk of low intake dehydration in cancer patients is influenced by age, albumin level, tumor duration, dysphagia, CASQ score, and BI score. The nomogram model effectively assesses the risk of low intake dehydration in these patients.