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Background: Patients with unprotected left main (UPLM) disease who underwent percutaneous coronary intervention (PCI) were found to have inconsistent results compared to those treated with coronary artery bypass grafting (CABG). Methods: We identified and enrolled randomized controlled trials (RCTs) and observational studies (OSs) comparing PCI versus CABG for UPLM disease. A meta-analysis was performed using Stata 17.0. The primary endpoints were major adverse cardiovascular and cerebrovascular events (MACCEs). Additionally, all-cause death, cardiac death, myocardial infarction (MI), stroke, target vessel revascularization (TVR), and stent thrombosis (ST) were included as secondary endpoints. The odds ratios and 95% confidence intervals (CIs) were calculated. Sensitivity analyses were implemented if I 2 > 50% or p < 0.01. Publication bias analysis was conducted if more than 10 studies were included. Results: A total of 5 RCTs and 18 OSs involving 35,409 patients were included. The CABG strategy had a significantly lower incidence of MACCEs, primarily due to TVR. A significantly lower stroke rate was observed with the PCI strategy, as well as a significantly lower all-cause death, cardiac death, MI, and ST rate compared with the CABG strategy. Conclusions: MACCE rates were significantly lower in patients who underwent CABG, primarily due to TVR, but stroke rates were higher. RCTs with different study types need further investigation to confirm the most effective strategy.
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Background: Side branch (SB) occlusion after main vessel stenting is the main complication in treating coronary bifurcation lesions by provisional stenting. The Jailed Wire Technique (JWT), recommended by the European Bifurcation Club, is a standard technique to deal with this issue. The Jailed Balloon Technique (JBT) has been found to be more effective than the JWT in clinical practice by some interventionists, but it has not been widely accepted. In this meta-analysis, we compared the efficacy and safety of JBT and JWT. Methods: The literature comparing JBT and JWT was systematically reviewed. Stata/MP 17.0 was used to perform a meta-analysis. The primary endpoints were major adverse cardiac events (MACE), cardiac death, myocardial infarction (MI) and target lesion revascularization (TLR). The secondary endpoints were SB occlusion and SB dissection. Aggregated odds ratios and 95% confidence intervals were calculated. A sensitivity analysis was conducted if I 2 was > 50% or p < 0.01. Results: Thirteen studies involving 1789 patients were enrolled. JBT was found to have a significantly lower incidence of MACE, SB occlusion and dissection. The incidence of cardiac death, MI and TLR were also lower in the JBT group, though the differences were not significant. Conclusions: JBT prevents SB occlusion more effectively and does not increase immediate or long-term complications. JBT, or its modified versions, can be used to treat SBs with a high risk of occlusion.
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Despite a decade of extensive research and clinical insights, percutaneous coronary intervention strategies for coronary bifurcation lesions have remained a challenging and highly debated area. This article presents a review of the latest findings and advances in defining and classifying coronary bifurcation lesions, in vitro studies, intracoronary imaging, stenting strategies, and the deployment of drug-coated balloons. Based on current evidence, this review provides recommendations for interventional cardiologists to develop individualized interventional strategies and enhance the efficiency of stenting procedures.
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Coronary bifurcation lesions remain one of the most challenging lesions for cardiology interventionists. The provisional stenting strategy has been regarded as the first option for most of these lesions. However, the main complication of this technique is side branch (SB) occlusion, which could lead to a peri-procedural myocardial infarction or even death. Various studies have focused on addressing this issue, but there are no definitive guidelines in the literature to treat these lesions. There isn't enough clinical evidence from randomized controlled trial or two-arm cohort studies to illustrate which techniques provide the best outcomes. In this review, we summarize the mechanisms, independent predictors and predictive models of SB occlusion, and review seventeen techniques involving SB protection and occlusion rescue. Every technique was evaluated according to related bench tests, clinical studies and our own clinical experiences. The aim of this review is to provide interventionists with new insights for the treatment of coronary bifurcation lesions.
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Background: Provisional stenting is the preferred strategy for non-left main bifurcation lesions. However, its superiority over planned double stenting for unprotected left main distal bifurcation (UPLMB) lesions remains unclear. Previous studies have reported conflicting results. Methods: Randomised controlled trials (RCTs) and observational studies comparing the outcomes of provisional stenting to planned double stenting for UPLMB lesions were identified. The primary endpoint was major adverse cardiac events (MACE). The secondary endpoints were myocardial infarction (MI), target vessel revascularisation (TVR), target lesion revascularisation (TLR), all-cause death, cardiac death and stent thrombosis (ST). Aggregated odds ratios (OR) and 95% confidence intervals were calculated. A sensitivity analysis was conducted if I 2 was > 50% or p < 0.01. Publication bias analysis was considered if more than 10 studies were enrolled. Results: Two RCTs and 19 observational studies comprising 11,672 patients were enrolled. Provisional stenting had a significantly lower incidence of MACE, mainly driven by TLR and TVR. Double stenting had a significantly lower incidence of cardiac death. In addition, patients undergoing provisional stenting had a lower tendency towards the occurrence of MI, while patients undergoing double stenting had a lower tendency towards all-cause death and ST. Conclusions: A provisional stenting strategy was associated with lower MACE, TVR and TLR but higher cardiac death. Further investigation is needed through RCTs to assess which strategy performs better.
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BACKGROUND: Both E2F transcription factor and cyclin-dependent kinases (CDKs), which increase or decrease E2F activity by phosphorylating E2F or its partner, are involved in the control of cell proliferation, and some circRNAs and miRNAs regulate the expression of E2F and CDKs. However, little is known about whether dysregulation among E2Fs, CDKs, circRNAs and miRNAs occurs in human PCa. METHODS: The expression levels of CDK13 in PCa tissues and different cell lines were determined by quantitative real-time PCR and Western blot analysis. In vitro and in vivo assays were preformed to explore the biological effects of CDK13 in PCa cells. Co-immunoprecipitation anlysis coupled with mass spectrometry was used to identify E2F5 interaction with CDK13. A CRISPR-Cas9 complex was used to activate endogenous CDK13 and circCDK13 expression. Furthermore, the mechanism of circCDK13 was investigated by using loss-of-function and gain-of-function assays in vitro and in vivo. RESULTS: Here we show that CDK13 is significantly upregulated in human PCa tissues. CDK13 depletion and overexpression in PCa cells decrease and increase, respectively, cell proliferation, and the pro-proliferation effect of CDK13 is strengthened by its interaction with E2F5. Mechanistically, transcriptional activation of endogenous CDK13, but not the forced expression of CDK13 by its expression vector, remarkably promotes E2F5 protein expression by facilitating circCDK13 formation. Further, the upregulation of E2F5 enhances CDK13 transcription and promotes circCDK13 biogenesis, which in turn sponges miR-212-5p/449a and thus relieves their repression of the E2F5 expression, subsequently leading to the upregulation of E2F5 expression and PCa cell proliferation. CONCLUSIONS: These findings suggest that CDK13 upregulation-induced formation of the positive feedback loop among circCDK13, miR-212-5p/miR-449a and E2F5 is responsible for PCa development. Targeting this newly identified regulatory axis may provide therapeutic benefit against PCa progression and drug resistance.
Asunto(s)
Proteína Quinasa CDC2/metabolismo , Factor de Transcripción E2F5/metabolismo , MicroARNs/metabolismo , Neoplasias de la Próstata/metabolismo , Proteína Quinasa CDC2/genética , Proliferación Celular/fisiología , Factor de Transcripción E2F5/genética , Retroalimentación , Femenino , Humanos , Masculino , MicroARNs/genética , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Transfección , Regulación hacia ArribaRESUMEN
p53, circRNAs and miRNAs are important components of the regulatory network that activates the EMT program in cancer metastasis. In prostate cancer (PCa), however, it has not been investigated whether and how p53 regulates EMT by circRNAs and miRNAs. Here we show that a Amotl1-derived circRNA, termed circAMOTL1L, is downregulated in human PCa, and that decreased circAMOTL1L facilitates PCa cell migration and invasion through downregulating E-cadherin and upregulating vimentin, thus leading to EMT and PCa progression. Mechanistically, we demonstrate that circAMOTL1L serves as a sponge for binding miR-193a-5p in PCa cells, relieving miR-193a-5p repression of Pcdha gene cluster (a subset of the cadherin superfamily members). Accordingly, dysregulation of the circAMOTL1L-miR-193a-5p-Pcdha8 regulatory pathway mediated by circAMOTL1L downregulation contributes to PCa growth in vivo. Further, we show that RBM25 binds directly to circAMOTL1L and induces its biogenesis, whereas p53 regulates EMT via direct activation of RBM25 gene. These findings have linked p53/RBM25-mediated circAMOTL1L-miR-193a-5p-Pcdha regulatory axis to EMT in metastatic progression of PCa. Targeting this newly identified regulatory axis provides a potential therapeutic strategy for aggressive PCa.