The clinical value of the Syntax score in patients with non-ST segment elevation myocardial infarction (NSTEMI) has been well established. The neutrophil-lymphocyte ratio (NLR), the platelet-lymphocyte ratio (PLR), the high sensitivity C-reactive protein (hsCRP)-albumin ratio (hsCAR), and systemic immune-inflammatory (SII) index are promising systemic inflammation (SI) biomarkers in coronary artery diseases. However, studies which compare the predicting value of these SI indicators with the Syntax score in NSTEMI patients are limited.NSTEMI patients who underwent coronary angiography (CAG) in our department were retrospectively enrolled. Both univariable and multivariable logistic regression analyses were performed to evaluate the clinical value between SI biomarkers and Syntax score in these patients. The area under the receiver operating characteristic curve (ROC) was used to compare the clinical values of these parameters in predicting 6-month major cardiovascular events (MACE) and over-all mortality.A total of 429 NSTEMI patients were finally enrolled in this study. The level of NLR, PLR, as well as hsCAR, and SII in patients with high Syntax scores, are significantly higher than patients with the low Syntax score. Multivariable logistic regression analysis demonstrated that all of the SI indicators but not the Syntax score were the independent risk factors of 6-month MACE in NSTEMI patients. ROC showed that all of the SI indicators had better predictive value than the Syntax score in these patients (0.637, 0.592, 0.631, 0.590, 0.559, respectively) in predicting MACE and similar predictive value in over-all mortality (0.530, 0.524, 0.761, 0.553, 0.620, respectively).Novel SI biomarkers including NLR, PLR, hsCAR, and SII have better predictive value in MACE and similar predictive value in over-all mortality compared with Syntax score in NSTEMI patients.
Abstract DNA Methylation can lead to abnormal gene expression. In the present study, we investigated whether the expression of methylated MFSD4A (major facilitator superfamily domain containing 4 A) was downregulated in nasopharyngeal carcinoma (NPC) and whether it is associated with malignant progression and poor prognosis of NPC. Bioinformatic analysis, bisulfite pyrosequencing, quantitative real-time reverse transcription PCR, and western blotting assays were performed to explore the relationship between hypermethylation of MFSD4A and its expression in NPC. The role of MFSD4A in NPC was verified by Cell Cycle Kit 8, transwell assays and flow cytometry in vitro and by animal experiments in vivo. Mass spectrometry, co-immunoprecipitation, and immunofluorescence assays were applied to explore the mechanism by which MFSD4A inhibits NPC. The prognostic significance of MFSD4A or EPHA2 was investigated by immunohistochemical analysis of clinical specimens. Hypermethylation of the promoter region of MFSD4A led to decreased expression of MFSD4A . When MFSD4A expression was upregulated or downregulated, the proliferation, apoptosis, migration, and invasion abilities of NPC cells were altered accordingly. Mechanistically, MFSD4A could specifically bind to and degrade EPH receptor A2 (EPHA2) by recruiting ring finger protein 149 (RNF149), which led to alterations in the EPHA2-mediated PI3K-AKT-ERK1/2 pathway and epithelial-mesenchymal transition (EMT), thereby affecting NPC progression. Clinically, high MFSD4A expression or low-EPHA2 expression was associated with better prognosis for patients with NPC. In all, reduced MFSD4A expression in NPC is caused by promoter hypermethylation. MFSD4A or EPHA2 expression is associated with the malignant biological behavior and prognosis of NPC. MFSD4A is a promising potential therapeutic target for NPC.
AbstractBackground: Platinum-based chemotherapy is important for the treatment for recurrent or metastatic nasopharyngeal carcinomas (RM-NPCs). However, the prognosis of RM-NPC patients remains poor. This study evaluated the efficacy and safety of vascular-targeting agentsplus chemotherapy for RM-NPC treatment. Methods: This observational clinical trial, conducted at seven hospitals in Guangxi between January 2017 and December 2021, included 198 patients (158 males [79.8%]; median age, 51 years [IQR, 45–57years]). Chemotherapy was administered with and without vascular-targeting agents in 66 and 132 patients, respectively. The primary endpoint was progression-free survival (PFS), assessed by a blinded independent review committee according to RECIST v.1.1. The secondary end points were overall survival (OS) and safety. Results: After a median follow-up of 20 months, 31 (47.0%) and 82 (62.1%) deaths occurred in the combination therapy and chemotherapy alone groups, respectively. Median PFS was significantly higher in the combination group (7.0 months [95% CI, 5.7–8.3 months]) than in the chemotherapy alone group (5.0 months [95% CI, 4.1–5.9 months], P = 0.034), with a hazard ratio of 0.73 (95% CI, 0.54–0.98). The combination group exhibited a higher median OS compared to the chemotherapy alone group (37 months [95% CI, 21.3–52.7] vs. 20 months [95% CI, 13.0–27.0months], P = 0.047), representing a hazard ratio of 0.66 (95% CI, 0.45–0.97). In the combination therapy group, the most common adverse events were hypertension (n = 10/66 [15.1%]). Conclusion: The addition of vascular-targeting agents to chemotherapy for RM-NPC patients provided superior efficacycompared to chemotherapy alone, along with a manageable safety profile.
CFTP is a software tool designed to aid programmers in hand-parallelizing sequential ANSI Fortran 77 or CFT code. It assists the programmer by providing information about the code which the programmer must have in order to determine where parallel execution is safe and where it is not. CFTP collects information regarding the input code's usage of its variables. In doing so it builds a call graph, and performs intra- and interprocedural def-use, use-def, and aliasing analysis. CFTP makes the results of these different forms of analysis directly available to the user.< >
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