Clinical application of ctDNA in early diagnosis, treatment and prognosis of patients with non-small cell lung cancer.

Lung cancer is one of the most common malignancies worldwide, with non-small cell lung cancer (NSCLC) being the most common type. As understanding of precise treatment options for NSCLC deepens, circulating tumor DNA (ctDNA) has emerged as a potential biomarker that has become a research hotspot and may represent a new approach for the individualized diagnosis and treatment of NSCLC. This article reviews the applications of ctDNA for the early screening of patients with NSCLC, guiding targeted therapy and immunotherapy, evaluating chemotherapy and postoperative efficacy, assessing prognosis and monitoring recurrence. With the in-depth study of the pathogenesis of NSCLC, plasma ctDNA may become an indispensable part of the precise treatment of NSCLC, which has great clinical application prospects.

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Advances in systemic immune inflammatory indices in non-small cell lung cancer: A review.

Lung cancer is one of the most prevalent cancers globally, with non-small cell lung cancers constituting the majority. These cancers have a high incidence and mortality rate. In recent years, a growing body of research has demonstrated the intricate link between inflammation and cancer, highlighting that inflammation and cancer are inextricably linked and that inflammation plays a pivotal role in cancer development, progression, and prognosis of cancer. The Systemic Immunoinflammatory Index (SII), comprising neutrophil, lymphocyte, and platelet counts, is a more comprehensive indicator of the host's systemic inflammation and immune status than a single inflammatory index. It is widely used in clinical practice due to its cost-effectiveness, simplicity, noninvasiveness, and ease of acquisition. This paper reviews the impact of SII on the development, progression, and prognosis of non-small cell lung cancer.

Pulsatile flow increases METTL14-induced m 6 A modification and attenuates septic cardiomyopathy: an experimental study.

INTRODUCTION: Septic cardiomyopathy is a sepsis-mediated cardiovascular complication with severe microcirculatory malperfusion. Emerging evidence has highlighted the protective effects of pulsatile flow in case of microcirculatory disturbance, yet the underlying mechanisms are still elusive. The objective of this study was to investigate the mechanisms of N 6 -methyladenosine (m 6 A) modification in the alleviation of septic cardiomyopathy associated with extracorporeal membrane oxygenation (ECMO)-generated pulsatile flow. METHODS: Rat model with septic cardiomyopathy was established and was supported under ECMO either with pulsatile or non-pulsatile flow. Peripheral perfusion index (PPI) and cardiac function parameters were measured using ultrasonography. Dot blot assay was applied to examine the m 6 A level, while qRT-PCR, Western blot, immunofluorescence, and immunohistochemistry were used to measure the expressions of related genes. RNA immunoprecipitation assay was performed to validate the interaction between molecules. RESULTS: The ECMO-generated pulsatile flow significantly elevates microcirculatory PPI, improves myocardial function, protects the endothelium, and prolongs survival in rat models with septic cardiomyopathy. The pulsatile flow mediates the METTL14-mediated m 6 A modification to zonula occludens-1 (ZO-1) mRNA (messenger RNA), which stabilizes the ZO-1 mRNA depending on the presence of YTHDF2. The pulsatile flow suppresses the PI3K-Akt signaling pathway, of which the downstream molecule Foxo1, a negative transcription factor of METTL14, binds to the METTL14 promoter and inhibits the METTL14-induced m 6 A modification. CONCLUSION: The ECMO-generated pulsatile flow increases METTL14-induced m 6 A modification in ZO-1 and attenuates the progression of septic cardiomyopathy, suggesting that pulsatility might be a new therapeutic strategy in septic cardiomyopathy by alleviating microcirculatory disturbance.

Imaging and pathological characteristics, treatment, and prognosis of pulmonary sequestration-A retrospective study of 13 cases.

OBJECTIVE: This study aimed to summarize and analyze the characteristics of pulmonary sequestration to improve our understanding of this disease. METHODS: Between January 2019 and April 2023, the clinical data of 13 patients with pulmonary sequestration underwent surgical treatment at the First Affiliated Hospital of Gannan Medical University. RESULTS: The male-to-female ratio was 4:9, the age was 0.5 to 60 years, and the average age was 38 ± 19 years. There were 10 and 3 cases of intralobar and extralobar pulmonary sequestration, respectively. Chest enhanced computed tomography (CT) and three-dimensional vascular reconstruction showed that the abnormal blood vessels were derived from the descending thoracic aorta in nine cases and from other blood vessels in four cases. Three patients underwent thoracoscopic lobectomy, two underwent thoracoscopic segmentectomy, and eight underwent thoracoscopic wedge resection. All the patients successfully completed the surgery and were discharged postoperatively. CONCLUSIONS: Some patients with pulmonary sequestration exhibit no obvious symptoms. Patients with clinical symptoms are easily confused for pneumonia, bronchial cysts, lung abscesses, and lung tumors; therefore, patients with pulmonary sequestration are prone to missed diagnosis and misdiagnosis. Currently, enhanced chest CT combined with three-dimensional vascular reconstruction can accurately show the course, branches, and relationship with the mass of the feeding artery. Routine pathological examination is helpful to further clarify the diagnosis of pulmonary sequestration. Minimally invasive thoracoscopic surgery is the preferred treatment for patients with pulmonary sequestration. Surgical resection is safe and feasible, and satisfactory results are typically obtained.

Platelet-rich plasma influence on the sternal wounds healing: A meta-analysis.

A meta-analysis research was executed to appraise the effect of platelet-rich plasma (PRP) on sternal wound healing (SWH). Inclusive literature research till April 2023 was done and 1098 interconnected researches were revised. The 11 picked researches, enclosed 8961 cardiac surgery (CS) persons were in the utilised researchers' starting point, 3663 of them were utilising PRP, and 5298 were control. Odds ratio (OR) and 95% confidence intervals (CIs) were utilised to appraise the effect of PRP on the SWH by the dichotomous approach and a fixed or random model. PRP had significantly lower sternal wound infection (SWI) (OR, 0.11; 95% CI, 0.03-0.34, p < 0.001), deep SWI (OR, 0.29; 95% CI, 0.16-0.51, p < 0.001), and superficial SWI (OR, 0.20; 95% CI, 0.13-0.33, p < 0.001), compared to control in CS persons. PRP had significantly lower SWI, deep SWI, and superficial SWI, compared to control in CS persons. However, caution must be taken when interacting with its values since there was a low sample size of some of the nominated research found for the comparisons in the meta-analysis.

APOC1 predicts a worse prognosis for esophageal squamous cell carcinoma and is associated with tumor immune infiltration during tumorigenesis.

Background: Esophageal carcinoma (ESCA), a common malignant tumor of the digestive tract with insidious onset, is a serious threat to human health. Despite multiple treatment modalities for patients with ESCA, the overall prognosis remains poor. Apolipoprotein C1 (APOC1) is involved in tumorigenesis as an inflammation-related molecule, and its role in esophageal cancer is still unknown. Methods: We downloaded documents and clinical data using The Cancer Genome Atlas (TCGA)and Gene Expression Omnibus (GEO) databases. We also conducted bioinformatics studies on the diagnostic value, prognostic value, and correlation between APOC1 and immune infiltrating cells in ESCA through STRING (https://cn.string-db.org/), the TISIDB (http://cis.hku.hk/TISIDB/) website, and various other analysis tools. Results: In patients with ESCA, APOC1 was significantly more highly expressed in tumor tissues than in normal tissues (p < 0.001). APOC1 could diagnose ESCA more accurately and determine the TNM stage and disease classification with high accuracy (area under the curve, AUC≥0.807). The results of the Kaplan-Meier curve analysis showed that APOC1 has prognostic value for esophageal squamous carcinoma (ESCC) (p = 0.043). Univariate analysis showed that high APOC1 expression in ESCC was significantly associated with worse overall survival (OS) (p = 0.043), and multivariate analysis shows that high APOC1 expression was an independent risk factor for the OS of patients with ESCC (p = 0.030). In addition, the GO (gene ontology)/KEGG (Kyoto encyclopedia of genes and genomes) analysis showed a concentration of gene enrichment in the regulation of T-cell activation, cornification, cytolysis, external side of the plasma membrane, MHC protein complex, MHC class II protein complex, serine-type peptidase activity, serine-type endopeptidase activity, Staphylococcus aureus infection, antigen processing and presentation, and graft-versus-host disease (all p < 0.001). GSEA (gene set enrichment analysis) showed that enrichment pathways such as immunoregulatory-interactions between a lymphoid and non-lymphoid cell (NES = 1.493, p. adj = 0.023, FDR = 0.017) and FCERI-mediated NF-KB activation (NES = 1.437, p. adj = 0.023, FDR = 0.017) were significantly enriched in APOC1-related phenotypes. In addition, APOC1 was significantly associated with tumor immune infiltrating cells and immune chemokines. Conclusion: APOC1 can be used as a prognostic biomarker for esophageal cancer. Furthermore, as a novel prognostic marker for patients with ESCC, it may have potential value for further investigation regarding the diagnosis and treatment of this group of patients.

Transcription factor Nrf2 binds to circRNAPIBF1 to regulate SOD2 in lung adenocarcinoma progression.

Emerging evidence indicates that circular RNAs (circRNAs) play important roles in disease development, especially in cancers. Analysis of circRNA expression microarrays from the Gene Expression Omnibus database revealed that circPIBF1 was highly upregulated in lung adenocarcinoma (LUAD). The main aim of this study was to probe the function of circPIBF1 in pyroptosis of LUAD cells and the signal transduction pathways involved. CircPIBF1 was significantly overexpressed in LUAD and was related to the dismal prognosis of patients with LUAD. CircPIBF1 could bind to nuclear factor erythroid 2-related factor 2 (Nrf2), which further promoted the expression of superoxide dismutase 2 (SOD2). In addition, Nrf2 was also observed to recruit histone acetyltransferase E1A binding protein p300 (EP300) to enhance H3K27ac modification of SOD2, thus modulating the Nrf2-Keap1 signaling pathway. Moreover, we found that knockdown of circPIBF1 significantly suppressed the expression of SOD2 in cells and LUAD cell growth, while enhanced the expression of pyroptosis-related factors, which were further reversed by overexpression of SOD2 or EP300. Collectively, our findings suggest a direct involvement of circPIBF1 in pyroptosis-related LUAD carcinogenesis and implicate a role of Nrf2/EP300/SOD2 signaling in this process.

CircFBXW7 Inhibits Proliferation, Migration, and Invasion of Nonsmall Cell Lung Cancer Cells by Regulating miR-492.

Background: CircFBXW7 has been determined to be involved in various cancers; however, its role in nonsmall cell lung cancer (NSCLC) remains unclear. This study examined the function and potential mechanism of circFBXW7 in NSCLC. Methods: The structure of circFBXW7 was verified via RT-PCR and Sanger sequencing. The expression of circFBXW7 in NSCLC was determined by qRT-PCR. The effect of circFBXW7 overexpression on the proliferation, migration, and invasion of NSCLC cells was examined by CCK-8 and Transwell assays. Furthermore, a circFBXW7-miRNA network was established to explore their interaction. Predicted miRNA was determined by qRT-PCR. Moreover, the miRNA mimics were synthesized, wherein its effect on proliferation, migration, and invasion of NSCLC cells overexpressed circFBXW7 was assessed. Results: The circularity of circFBXW7 was verified. The expression of circFBXW7 was found to be downregulated in NSCLC cells compared with that in normal human lung epithelial BEAS-2B cells. Overexpression of circFBXW7 reduced cell proliferation, migration, and invasion. Furthermore, according to the circFBXW7-miRNA network prediction and qRT-PCR validation, miR-492 was identified to be the target of circFBXW7. The inhibitory effect of circFBXW7 overexpression on cell proliferation, migration, and invasion was reversed by miR-492 mimics. Conclusion: CircFBXW7 is downregulated in NSCLC. CircFBXW7 inhibits NSCLC cells proliferation, migration, and invasion by regulating miR-492.

LncRNA MBLN1-AS1 inhibits the progression of retinoblastoma through targeting miR-338-5p-Wnt/ß-catenin signaling pathway.

OBJECTIVE AND DESIGN: Retinoblastoma is the most common primary intraocular malignancy of childhood, which brings a heavy burden to the countries across the world, especially the developing countries. It has been shown that lncRNA muscleblind-like 1 antisense RNA 1 (MBNL1-AS1) exerts anti-tumor effects in various cancers, including bladder cancer, papillary thyroid cancer, and retinoblastoma. In the present study, we hypothesized that MBNL1-AS1 might play a protective role against retinoblastoma. METHODS: The expression of MBNL1-AS1 and its potential target miR-338-5p were evaluated in retinoblastoma cell line by real-time quantitative PCR and western blot. The involvement of MBNL1-AS1-miR-338-5p in the cell proliferation was evaluated by cell counting kit-8 (CCK8), and colony formation assay. The cell migration was evaluated by Transwell assay in Y79 cells, a retinoblastoma cell line. The involvement of MBNL1-AS1-miR-338-5p in tumor formation was also evaluated in mice. RESULTS: It was found that MBNL1-AS1 overexpression inhibited proliferation and migration in Y79 cells. In addition, the inhibitory effects of MBNL1-AS1 on Y79 cells were significantly reversed in the presence of miR-338-5p mimics, and MBNL1-AS1 overexpression significantly decreased miR-338-5p level in Y79 cells. Furthermore, MBNL1-AS1 overexpression significantly inhibited Wnt/ß-catenin signaling pathway, and this inhibitory effect was almost lost in the presence of miR-338-5p mimics. Finally, our in vivo study showed that MBNL1-AS1 overexpression significantly inhibited Y79-induced retinoblastoma in mice, and this inhibitory effect was lost in the presence of miR-338-5p mimics. CONCLUSION: Our study shows that MBNL1-AS1 exerts its anti-tumor effect by targeting miR-338-5p, thereby inactivating wnt/ß-catenin signaling pathway in retinoblastoma.

Peripheral blood inflammation indices are effective predictors of anastomotic leakage in elective esophageal surgery.

BACKGROUND: This study investigated the predictive value of peripheral inflammatory indices, including neutrophil count, lymphocyte count, platelet count, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR), in anastomotic leakage during elective esophageal surgery. METHODS: This retrospective study included all patients who underwent esophagectomy for esophageal squamous cell carcinoma from 2016 to 2020 in our institution. The peripheral blood inflammatory indices were obtained on preoperative days 1-7 (PRD 1-7), and postoperative days 1-3 (POD 1-3) and 4-7 (POD 4-7). Univariate, multivariate logistic, and receiver operating characteristic curve analyses were conducted to evaluate the diagnostic value of these peripheral blood inflammatory indices. RESULTS: A total of 198 patients were included in the study, and 25 (13%) patients experienced anastomotic leakage. Multivariate analyses identified diet, neutrophil count, and PLR on POD 1-3, and NLR on POD 4-7 as independent factors associated with anastomotic leakage. Using the receiver operating characteristic curve, the variable with the best area under curve was a neutrophil cutoff count of 4.1 [0.737; 95% CI: 0.639-0.835], with a sensitivity and specificity of 60.0% and 66.5%, respectively. This was followed by an NLR cutoff value of 9.5 on POD 4-7 (0.628; 95% CI: 0.505-0.752) and a cutoff PLR value of 220.1 on POD 1-3 (0.643; 95% CI: 0.536-0.750). Diet showed a poor result on the receiver operating characteristic curve analysis. CONCLUSIONS: Neutrophil count and PLR on POD 1-3 and NLR on POD 4-7 were shown to have predictive value for anastomotic leakage in elective esophageal surgery.