Revista De Investigacion Clinica-Clinical and Translational Investigation最新文献

Background: Accurate segmentation of blood vessels in glioma pathological images is crucial for understanding tumor vasculature and progression, yet remains challenging due to complex vessel morphology and image variations.

Objective: This study aimed to develop and evaluate a novel approach using a finetuned masked autoencoder self-attention mechanism (MedSAM) framework for interactive segmentation of glioma blood vessels in pathological images called GliomaVascularSAM.

Methods: We utilized a dataset of 2632 image patches derived from multiple glioma datasets. These patches were obtained from tissue samples of 879 patients from The Cancer Genome Atlas and 179 patients from three hospitals. The performance of GliomaVascularSAM was compared with convolutional neural network-based models (including nnU-Net, Pathology-nnU-Net, and nnSAM) and SAM-based segmentation methods. Model performance was evaluated using the dice similarity coefficient, sensitivity, and positive predictive value.

Results: The proposed GliomaVascularSAM outperformed traditional-based models, achieving a dice similarity coefficient of 0.784, sensitivity of 0.767, and positive predictive value of 0.820. Compared with the nnU-Net model (dice similarity coefficient: 0.652), our approach yielded a 13.2% improvement.

Conclusion: GliomaVascularSAM significantly enhanced the accuracy and interactivity of glioma blood vessel segmentation in pathological images. This approach can assist clinicians in the precise analysis of glioma vasculature, thereby contributing to improved diagnosis and management of patients with glioma.

Background: Interleukin-18 (IL-18) is a key inflammasome-related cytokine implicated in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

Objective: This study investigated the diagnostic, prognostic, and immunogenetic relevance of IL-18 and its promoter polymorphism (-607C/A, rs1946518) in COVID-19 susceptibility, severity, and mortality among Kurdish coronavirus disease-2019 (COVID-19) patients.

Methods: A total of 100 unvaccinated COVID-19 patients and 80 healthy controls (HCs) were enrolled. COVID-19 patients were further classified into non-severe (n=60) and severe cases (n=40), and additionally into survived (n=75) and non-survived groups (n=25). Biochemical markers, CURB-65 scores, and clinical outcomes (severity and survival) were assessed. Genotyping of the IL-18 -607C/A polymorphism was performed using polymerase chain reaction - sequence-specific primer (PCR-SSP).

Results: COVID-19 patients exhibited markedly elevated IL-18 levels compared with HCs (509.1 vs. 228.8pg/mL, p<0.001). IL-18 showed a strong positive correlation with disease severity (r=0.77, p<0.001) and significantly distinguished non-severe from severe cases and survivors from non-survivors (both p<0.001). Severe and non-survived patients demonstrated higher D-dimer, ferritin, C-reactive protein (CRP), fibrinogen, neutrophils, and CURB-65 scores, alongside lower lymphocyte counts. Genotype analysis revealed that the CC genotype was significantly associated with higher IL-18 expression and more severe clinical phenotypes, including elevated CURB-65 scores and inflammatory biomarkers. In contrast, the A allele (CA and AA genotypes) conferred strong protection against severe disease (AA: OR=0.053; CA: OR=0.149) but showed no significant association with mortality. Statistical tests confirmed pronounced genotype-dependent differences in IL-18, D-dimer, ferritin, CRP, leukocyte profiles, and fibrinogen (p<0.05). Diagnostic evaluation showed that IL-18 accurately discriminated COVID-19 cases from HCs (area under curve (AUC)=0.991; sensitivity 95.0%; specificity 95.06%). As a prognostic marker for severe disease, IL-18 demonstrated moderate performance (AUC=0.671).

Conclusion: The IL-18 -607C/A polymorphism influences COVID-19 susceptibility and severity, CC increases risk, while the A allele is protective, but it is not associated with mortality. IL-18 shows excellent diagnostic and moderate prognostic value and may enhance COVID-19 risk-stratification when combined with CURB-65 and genotypic data.

Background: Asthma is a common chronic respiratory disease characterized by persistent airway inflammation. This study investigated the role of cinnamic acid (CA) in an in vitro model of asthma and its mechanisms.

Methods: Human small airway epithelial cells (HSAECs) were stimulated with platelet-activating factor (PAF), then exposed to CA (20, 50, or 100μM). Cell viability and apoptosis were assessed using CCK-8 assay and flow cytometry. Inflammatory cytokine levels were measured by ELISA. Barrier function was evaluated via lucifer yellow permeability assay. Western blotting and RT-qPCR were used to measure levels of TGF-β1 pathway-related factors. To investigate whether CA acts through TGF-β1 inhibition, PAF-treated cells were co-incubated with CA and TGF-β1.

Results: CA treatment significantly reduced PAF-induced apoptosis in HSAECs. It also attenuated the PAF-induced upregulation of TNF-α, IL-1β, and IL-6 levels as well as the downregulation of PGE2 levels. CA improved epithelial barrier function by reducing permeability. CA downregulated TGF-β1 and Smad4 levels and inhibited Smad2 and Smad3 phosphorylation. Exogenous activation of TGF-β1 abolished the protective effects of CA against apoptosis, inflammation, and barrier integrity.

Conclusion: Our findings demonstrate that CA inhibits apoptosis, inflammation, and barrier dysfunction in asthmatic airway cells by inhibiting the TGF-β1/Smad pathway.

Objective: Non-small cell lung cancer (NSCLC) represents over 85% of lung cancer diagnoses and is a leading cause of cancer-related mortality worldwide. The study investigated the role of microRNA-138-2-3p (miR-138-2-3p) in regulating NSCLC cell migration, invasion, and epithelial-mesenchymal transition (EMT).

Methods: MiR-138-2-3p and target gene expression were measured by RT-qPCR or western blotting. Cell viability, migration, and invasion were analyzed using cell counting kit-8, wound healing, and Transwell assays. RNA pull-down assays were performed to determine the enrichment of antizyme inhibitor 1 (AZIN1) by biotinylated miR-138-2-3p, while luciferase reporter assay confirmed direct binding between miR-138-2-3p and AZIN1.

Results: MiR-138-2-3p was significantly downregulated in NSCLC cells and tissues. Its overexpression markedly suppressed NSCLC cell viability, migration, invasion, and epithelial-mesenchymal transition. AZIN1 was upregulated in NSCLC cells and tissues and directly targeted by miR-138-2-3p via binding to its 3'untranslated region, showing a negative correlation in expression. Moreover, AZIN1 overexpression reversed the suppressive effects of miR-138-2-3p on the malignant phenotype in NSCLC cells. Notably, bioinformatics analysis shows that lung adenocarcinoma patients with high AZIN1 expression exhibit significantly worse overall survival than those with low AZIN1 expression.

Conclusion: The results suggest that miR-138-2-3p inhibits the malignant phenotype of NSCLC cells by targeting AZIN1.

Background: The efficacy and safety of thrombolytics within the first 4.5h of ischemic stroke symptom onset are well documented; however, evidence beyond this timeframe remains contentious.

Objective: To assess the efficacy and safety of delayed thrombolysis (4.5-24-h window) for ischemic stroke.

Methods: We conducted a systematic search to identify studies comparing thrombolytics to placebo or standard care in ischemic stroke patients treated within 4.5-24h of symptom onset. The primary outcome was functional independence at 90 days, with additional efficacy outcomes exploring recanalization and reperfusion at 24h, as well as safety outcomes of 90-day mortality and symptomatic intracranial hemorrhage. The statistical analysis was performed using R studio.

Results: We included five randomized controlled trials with 1398 patients. The mean age was 70.2 years, 61% were male, and the median NIHSS score was 10.2. Compared with controls, thrombolysis improved functional independence at 90 days (OR 1.32; 95% CI: 1.06-1.63; p=0.01; I²=0%), although it increased the risk of symptomatic intracranial hemorrhage (OR 2.5; 95% CI: 1.10-5.71; p=0.02; I²=0%). No significant difference in mortality at 90 days was observed (OR 1.15; 95% CI: 0.84-1.57; p=0.39; I²=0%).

Conclusions: In ischemic stroke, thrombolytics administered within 4.5-24h improve functional independence at 90 days, also increasing the risk of symptomatic intracranial hemorrhage. At this point, careful and individualized patient selection, including advanced imaging, is mandatory for thrombolysis beyond the conventional 4.5-h treatment window.

Background: Sepsis, a systemic inflammatory response to acute infections.

Objective: We aimed to explore the associations of coagulation function indicators and intestinal function impairment markers with clinical outcomes in septic patients with gastrointestinal dysfunction.

Methods: Subjects (n=105) were selected from septic patients with gastrointestinal dysfunction treated between January 2022 and December 2024. Detection of coagulation function indicators [platelets (PLT), fibrinogen (Fib), and D-dimer (D-D)] and intestinal function impairment markers [endotoxin (ET) and d-lactate (d-Lac)] was completed on the day of admission. Patients were divided into two groups based on their 28 day survival status (dead or alive): a group of patients that died and survival group.

Results: The APACHE II score, SOFA score, D-D and d-Lac were influencing factors of clinical outcomes (P<0.05). The sensitivity and specificity of Fib, D-D, ET and d-Lac alone and their combination for predicting death were 67.44%, 74.42%, 81.40%, 65.17% and 77.74%, and 75.81%, 74.19%, 67.74%, 75.81% and 83.87%, respectively, and the areas under the curves were 0.737, 0.815, 0.779, 0.748 and 0.868, respectively (P<0.05).

Conclusion: The coagulation function indicators and intestinal function impairment markers have associations with the clinical outcomes in septic patients with gastrointestinal dysfunction.

Between 1949 and 1964, advancements in chemistry and medicine, along with societal demands, made fertility regulation possible. Most of the chemical work occurred outside traditional centers, and it was at Syntex S.A. in Mexico City that the pioneering work of George Rosenkranz, Carl Djerassi, and Luis Miramontes achieved a breakthrough, resulting in the synthesis of norethindrone (19-nor-17α-ethynyl testosterone) on October 15, 1951. This compound was a potent and orally active progestogen, establishing the basis for modern contraception. Meanwhile, Syntex's simultaneous success in synthesizing cortisone from diosgenin (a compound found in Mexican yams) demonstrated how an industrial laboratory in a developing scientific country could compete with and outperform better-funded international rivals. Meanwhile, across the border, research on contraceptive steroids gained momentum. Frank B. Colton (G.D. Searle) synthesized norethynodrel in the United States, which became the first FDA-approved oral contraceptive in 1960. However, history would restore its balance. In fact, norethindrone and its derivatives from Syntex were soon available worldwide, becoming the most widely used progestins in oral contraceptives. This review examines the interactions between scientific and social history, clarifying the roles of key figures and situating Mexico's contributions within a broader global context of reproductive autonomy.

Background: As a first-line chemotherapy agent for colorectal cancer (CRC), oxaliplatin suffers from limited efficacy due to acquired resistance. This study investigated whether geniposide can overcome oxaliplatin resistance in preclinical models and elucidated the underlying molecular mechanisms.

Methods: We employed MTT, colony formation, flow cytometry, wound healing, and Transwell assays to evaluate viability, proliferation, apoptosis, migration, and invasion in oxaliplatin-resistant CRC cells (SW480/R, LoVo/R) treated with geniposide and/or oxaliplatin. Xenograft models bearing SW480/R or LoVo/R tumors were established to assess in vivo efficacy. Immunofluorescence analysis quantified Ki67-positive proliferating cells, while Western blot measured apoptosis markers (Bax, Bcl-2) and PI3K/AKT/mTOR pathway activity.

Results: Geniposide-oxaliplatin combination therapy significantly inhibited proliferation, migration, and invasion while inducing apoptosis in resistant CRC cells beyond monotherapy effects. In vivo, geniposide restored oxaliplatin sensitivity, substantially reducing tumor growth and Ki67 proliferation index. Mechanistically, geniposide suppressed phosphorylation of AKT and mTOR in both cellular and xenograft models, with maximal inhibition observed in combination groups.

Conclusion: Geniposide reverses oxaliplatin resistance in CRC through PI3K/AKT pathway inhibition, demonstrating that geniposide-oxaliplatin combination therapy represents a promising therapeutic strategy for oxaliplatin-resistant CRC. .