Ten-year outcomes after percutaneous coronary intervention versus coronary artery bypass grafting for multivessel or left main coronary artery disease: a systematic review and meta-analysis.

BACKGROUND: Short-term and long-term comparative outcomes after percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for multivessel coronary artery (MVCA) or left main coronary artery (LMCA) disease are highly debated. GOALS: We performed a meta-analysis to evaluate the difference between PCI and CABG for the treatment of patients with MVCA or LMCA in long-term follow-up. METHODS: Literatures were searched in PubMed, EMBASE and The Cochrane Library from January 1, 2000 to January 1, 2021, including RCTs and observational studies (OSs). The primary outcome was all-cause mortality at 10 years follow-up, and the secondary outcomes included cardiac mortality, repeated revascularization, myocardial infarction, and stroke. RESULTS: A total of 5 RCTs reporting data from 3013 participants and 4 OSs of 5608 participants were included for analysis. There was no significant difference between PCI and CABG in all-cause mortality (Odds Ratio (OR) 1.03 [95% confidence interval (CI) 0.89 to 1.19]), whereas PCI was associated with higher cardiac mortality (OR 0.76 [95% CI 0.65 to 0.90]) and repeated revascularization rate comparing to CABG (OR 1.77 [95% CI 1.08 to 2.89]; I2 = 94.61%). The difference between PCI and CABG in repeated revascularization in either RCTs or OSs, in myocardial infarction in either RCTs or OSs were not significant. In OSs, stroke rate in PCI group was lower than those in CABG, but not in RCTs. There was a significant increase of stroke rate in CABG comparing to PCI (OR 0.65 [95% CI 0.53 to 0.80]; I2 = 0.00%). No significant difference between PCI and CABG in myocardial infarction was not observed (OR 0.92 [95% CI 0.64 to 1.31]; I2 = 57.84%). CONCLUSION: Evidence from our study and prior studies suggested the superiority of CABG over PCI in improving 5- but not 10-year survival among patients with MVCA. In the contrast, there was no significant difference between CABG and PCI for treating patients with LMCA in either 5- or 10-year survival rate. More long-term trials are needed to better define differences of outcome between 2 techniques.

SERPINE1 Overexpression Promotes Malignant Progression and Poor Prognosis of Gastric Cancer.

The serine protease inhibitor clade E member 1 (SERPINE1) is a major inhibitor of tissue plasminogen activator and urokinase, and has been implicated in the development and progression of a variety of tumors. In this study, mRNA microarray and TCGA database were used to comprehensively analyze the upregulation of SERPINE1 in gastric cancer (GC) tissues compared with the normal stomach tissues. Kaplan-Meier results confirmed that patients with high SERPINE1 expression exhibited worse overall survival and disease-free survival. In addition, cell proliferation, cell scratches, transwell migration and invasion assay showed that SERPINE1 knockdown inhibited the proliferation, migration and invasion of GC ells. Western blot showed that the expression of VEGF and IL-6 was significantly upregulated after overexpression of SERPINE1. Meanwhile, SERPINE1 was positively correlated with the level of immune infiltration using the online analysis tools TISIDB and TIMER. And SERPINE1 expression increased with the increase of malignancy of GC which were detected by Immunohistochemistry. Finally, tumorigenesis experiments in nude mice further demonstrated that SERPINE1 could promote the occurrence and development of GC, while deletion of SERPINE1 inhibited the progression of GC. In summary, SERPINE1 was highly expressed in GC tissues, and SERPINE1 was helpful for differential diagnosis of pathological grade of gastric mucosal lesions. SERPINE1 might regulate the expression of VEGF and IL-6 through the VEGF signaling pathway and JAK-STAT3 inflammatory signaling pathway, thus ultimately affecting the invasion and migration of GC cells.

Comprehensive bioinformatics analyses identified Homeobox B9 as a potential prognostic biomarker and therapeutic target for gastric cancer.

BACKGROUND: The Homeobox B (HOXB) family promotes tumor progression, but the mechanism of its action in gastric cancer (GC) is unclear. We sought to identify the HOXB family members that are critical to the prognosis of GC patients. METHODS: The Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), cBioPortal, UALCAN, Kaplan-Meier plotter, and the GeneMANIA databases were used to analyze the messenger RNA (mRNA) expression levels, prognostic value, and gene-gene interaction network of the HOXB9 family members in GC. The expression of HOXB9 in GC and its relationship with various clinicopathological parameters and the prognosis of patients were verified by immunohistochemistry. RESULTS: The expression of HOXB3, HOXB5, HOXB6, HOXB7, HOXB9, and HOXB13 mRNA was significantly upregulated in GC. There was a significant correlation between the upregulation of HOXB3, HOXB5, and HOXB9 mRNA and a low overall survival (OS) rate. The high expression of HOXB7, HOXB9, and HOXB13 mRNA was closely correlated to tumor grade and stage. HOXB9 was the HOXB family member most closely related to the occurrence and development of GC. A further analysis showed that HOXB9 might be involved in deoxyribonucleic acid repair and division regulation. A validation study showed that the advanced cancer group had a higher level of HOXB9 expression than the early cancer group. The high expression of HOXB9 in gastric tissue plays an important role in the survival and prognosis of GC patients. CONCLUSIONS: HOXB family members have different degrees of abnormal expression in GC. High HOXB9 expression in GC tissues was significantly correlated with a worse prognosis. Thus, HOXB9 is a potential novel biomarker and therapeutic target for GC.

Circular RNA circ_0029589 regulates proliferation, migration, invasion, and apoptosis in ox-LDL-stimulated VSMCs by regulating miR-424-5p/IGF2 axis.

BACKGROUND: Circular RNAs (circRNAs) have been identified to be critical mediators in the progression of atherosclerosis (AS). However, the exact roles and molecular mechanism of circ_0029589 in AS are far from understood. METHODS: Vascular smooth muscle cells (VSMCs) stimulated by oxidized low-density lipoprotein (ox-LDL) were served as a cellular model of AS. The expression levels of circ_0029589, microRNA (miR)-424-5p, and insulin-like growth factor 2 (IGF2) were measured by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot analysis. Cell proliferation was determined by Cell Counting Kit-8 (CCK-8) assay and colony formation assay. Cell apoptosis, migration and invasion were examined by flow cytometry and transwell assay. The relationship between miR-424-5p and circ_0029589 or IGF2 was predicted by starbase and verified by dual-luciferase reporter assay. RESULTS: Circ_0029589 and IGF2 were upregulated and miR-424-5p was downregulated in VSMCs treated with ox-LDL. Silence of circ_0029589 inhibited proliferation, migration and invasion but induced apoptosis in ox-LDL-treated VSMCs. MiR-424-5p was a target of circ_0029589 and its knockdown reversed the effects of circ_0029589 interference on proliferation, migration, invasion, and apoptosis in ox-LDL-stimulated VSMCs. IGF2 was a target of miR-424-5p and miR-424-5p overexpression suppressed proliferation, migration and invasion while promoted apoptosis in ox-LDL-treated VSMCs by downregulating IGF2. Circ_0029589 positively modulated IGF2 expression by sponging miR-424-5p. CONCLUSION: Circ_0029589 silence might inhibit the progression of AS by regulating miR-424-5p/IGF2 axis, providing a novel mechanism for pathogenesis of AS.

Bifunctional pyridoxal derivatives as efficient bioorthogonal reagents for biomacromolecule modifications.

Two types of pyridoxal analogs, azido pyridoxal (PL-N3) and carboxyl pyridoxal (PL-COOH), were developed as novel bifunctional bioorthogonal molecules. These molecules showed fast imine formation with hydrazinyl groups and stable covalent linkages via azido/carboxyl groups, and thus were of great use for site-specific peptide and protein modifications.