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

Background: Coronary artery disease (CAD) remains a leading cause of morbidity and mortality worldwide. Conventional CCTA has limited ability to evaluate functional significance of stenosis, highlighting the need for non-invasive physiological assessment methods.

Objective: This study aimed to assess the diagnostic performance of a CT-FFR algorithm based on CFD in identifying ischemic coronary artery stenosis.

Methods: A total of 184 vessels from 171 patients undergoing both CCTA and ICA were retrospectively analyzed. CT-FFR and QFR were computed, with QFR ≤0.8 serving as the reference standard for ischemia. The diagnostic capabilities of CT-FFR were compared with anatomical evaluation via CCTA.

Results: CT-FFR demonstrated superior diagnostic performance over CCTA, with per-vessel sensitivity of 95.5%, specificity of 74.2%, and accuracy of 91.8% (AUC: 0.839 vs. 0.637, P<0.001). In lesions with intermediate QFR values (0.75-0.85), CT-FFR maintained high diagnostic accuracy (79.4%) and AUC (0.785), outperforming CCTA. Furthermore, CT-FFR remained reliable across various calcification levels, with diagnostic efficacy unaffected by Agatston scores.

Conclusion: CT-FFR based on CFD offers a robust, non-invasive solution for the functional assessment of coronary stenosis. Its diagnostic superiority over CCTA and consistent performance in calcified vessels highlight its clinical utility in precision cardiovascular care.

Background: Circ-CCDC66 (circular-Coiled-coil domain-containing protein 66) has been implicated in therapy resistance in colorectal and gastric cancers, but its role in breast cancer remains poorly understood.

Objective: This study aimed to explore the functional role and underlying mechanism of circ-CCDC66 in breast cancer proliferation and stem cell spheroidization.

Methods: The circular structure of circ-CCDC66 was verified using agarose gel electrophoresis and Sanger sequencing. Gene expression was assessed by RT-qPCR. Functional assays, including CCK-8 (Cell Counting Kit-8), colony formation, flow cytometry, and spheroidization, were performed following circ-CCDC66 overexpression in breast cancer cells. RNA sequencing and bioinformatics tools (LNCeVar, starBase, LncACTdb 2.0, Cytoscape) were used to construct a circ-CCDC66-miR-4259-CCDC66 regulatory network. Western blotting, luciferase reporter assays, and co-immunoprecipitation-qPCR (CO-IP-qPCR) were used to confirm molecular interactions.

Results: Circ-CCDC66 was highly expressed in breast cancer tissues and cell lines, particularly in MDA-MB-468 and MDA-MB-231 cells. Overexpression of circ-CCDC66 significantly promoted breast cancer cell proliferation and stem cell spheroidization. Mechanistically, circ-CCDC66 acted as a molecular sponge for miR-4259, thereby upregulating CCDC66 expression. This regulatory axis was confirmed through luciferase and CO-IP-qPCR assays.

Conclusions: circ-CCDC66 promotes breast cancer progression by regulating the miR-4259/CCDC66 axis. This novel pathway may serve as a potential therapeutic target for breast cancer treatment.

The pandemic character of coronavirus disease-19 (COVID-19) requires strategy changes designed to guarantee the safety of patients and health-care professionals. We are greatly concerned by the limitations in the operation of pulmonary function test (PFT) laboratories, since there is a high risk of disease progression in patients with chronic pulmonary diseases, and we are now faced by the influx of a new group of individuals in the recovery phase of post-COVID-19-syndrome that requires evaluation and follow-up of their respiratory function. To reestablish the operation of PFT laboratories limiting the risk of cross-contamination, we herein present the consensus reached by a group of experts in respiratory physiology, most of whom work in PFT laboratories in several Latin-American countries, on the applicable recommendations for severe acute respiratory syndrome coronavirus 2 pneumonia survivors when undergoing PFT. We present the safety and hygiene measures that must be adopted in laboratories or centers where PFT is conducted in adults and/or children. These recommendations answer the following questions: which PFT is most recommended in subjects that have recovered from COVID-19; what quality control and safety measures should PFT laboratories implement during this pandemic? And how should we approach non-COVID-19 patients requiring PFT?

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is commonly linked to liver fibrosis, which may progress to cirrhosis. FIB-4, APRI, and NFS are used to predict fibrosis severity, but their accuracy and role in long-term outcomes remain unclear.

Objectives: This study evaluates the predictive value of these scores for fibrosis and assesses the incidence of de novo cirrhosis and survival outcomes in MASLD patients.

Methods: This retrospective, single-center study included 175 MASLD patients in our university medical center. The diagnostic performance of FIB-4, APRI, and NFS for advanced fibrosis (stage 3-4) was assessed using receiver operating characteristic (ROC) analysis. Cox regression analysis was performed to evaluate factors associated with de novo cirrhosis and survival outcomes.

Results: The mean age was 49.9±14.1 years, and 54.9% were female. The median follow-up was 78 months. ROC analysis showed FIB-4 (AUC: 0.77) was the best predictor of advanced fibrosis, followed by APRI (AUC: 0.74) and NFS (AUC: 0.74). Multivariate analysis identified fibrosis stage (HR: 3.045, p=0.001) and hypertension (HR: 4.096, p=0.047) as independent predictors of de novo cirrhosis. Age (HR: 1.070, p=0.031), albumin (HR: 15.151, p<0.001), and HbA1c (HR: 1.589, p<0.001) were independently associated with survival.

Conclusion: FIB-4 was the most accurate predictor of advanced fibrosis. Fibrosis stage and hypertension were the strongest predictors of de novo cirrhosis. These findings highlight the importance of fibrosis staging and comorbidity management in MASLD.

Background: Anemia of inflammation (AI) is a mild form of anemia. Vitamin D deficiency has been linked to an increased risk of AI. This study aims to investigate the potential molecular mechanisms underlying the protective role of vitamin D in AI.

Methods: HepG2 cells were stimulated with lipopolysaccharide (LPS) to induce an inflammatory model in vitro. Cell counting kit-8 assays were conducted to assess vitamin D's cytotoxicity to HepG2 cells. RT-qPCR analysis was conducted to evaluate hepcidin mRNA levels. A rat AI model was established by subcutaneous injection of complete Freund's adjuvant (CFA). Hematoxylin-eosin staining was performed for synovial histopathological analysis. The concentrations of inflammatory cytokines were determined by ELISA. Western blotting was used to evaluate the protein levels of hepcidin, ferroportin, and markers associated with signaling pathways.

Results: Vitamin D dose-dependently reduced hepcidin expression in LPS-treated HepG2 cells. Vitamin D inactivated NF-κB, JAK2/STAT3, and BMP6/SMAD pathways to reduce hepcidin levels in LPS-treated HepG2 cells. Vitamin D ameliorated CFA-induced synovial injury and inflammatory response in rats. Vitamin D reduced hepcidin expression and improved anemia in CFA-injected rats. Vitamin D inactivated NF-κB, JAK2/STAT3, and BMP6/SMAD pathways in the liver of CFA-injected rats.

Conclusion: Vitamin D supplementation ameliorates experimental AI by downregulating hepcidin expression through NF-κB, JAK2/STAT3, and BMP6/SMAD pathways.

Polycystic ovary syndrome (PCOS) is a multifactorial endocrine and metabolic disorder in women of reproductive age characterized by hormonal imbalances, menstrual irregularities, and changes in ovarian morphology. Excess body fat plays a significant role in the clinical development of PCOS. The complex relationship between adiposity and PCOS involves disruptions in hormonal balance and inflammatory processes, which both contribute to the clinical and phenotypic manifestations of the syndrome. Insulin resistance is a significant factor linking adiposity and PCOS. Moreover, reduced fertility is associated with adiposity in PCOS, with obesity exacerbating anovulation. Recent studies have raised questions about the role of androgen exposure during fetal life, including genetic factors related to PCOS identified in genome-wide association studies and Mendelian randomization studies. Managing PCOS should concentrate on addressing adiposity as a crucial target, positively impacting the syndrome, particularly regarding reproductive and fertility outcomes. This review aims to understand how metabolic conditions such as obesity and insulin resistance are linked to PCOS and how early prenatal androgen exposure is involved in its etiology. Particular attention is given to its role in developmental programming, fat distribution, and fat type, as well as how these factors contribute to the onset of metabolic disturbances in adulthood.

Background: Sepsis is a severe condition in clinical practice. Although numerous studies have reported various prognostic markers associated with sepsis, the combination of the platelet-to-albumin ratio (PLT/ALB) and the lactate dehydrogenase-to-albumin ratio (LDH/ALB) has not been thoroughly examined.

Objectives: To study the associations of both the PLT/ALB ratio and the LDH/ALB ratio with all-cause mortality during the first hospitalization for sepsis.

Methods: A retrospective study was conducted on patients with sepsis at a local medical center. The ratios of PLT/ALB and LDH/ALB at the time of the first hospital admission of the patients were collected. Statistical analysis was used to examine the relationships of the PLT/ALB and LDH/ALB ratios with mortality, as well as their ability to predict the prognosis of patients with sepsis.

Results: Cox regression revealed that high PLT/ALB and LDH/ALB independently predict mortality. ROC curve analysis revealed that the ratios of PLT/ALB and LDH/ALB exhibited satisfactory sensitivity and specificity in predicting the mortality rate of patients with sepsis, with sensitivity values of 70.50% and 66.19% and specificity values of 73.58% and 69.25%, respectively.

Conclusion: Elevated ratios of PLT/ALB and LDH/ALB in sepsis patients are associated with increased all-cause mortality and serve as reliable prognostic indicators.