RESUMO
Background: Heart failure is the end stage of all cardiovascular diseases, which brings a heavy burden to the global health network. Arotinolol, as a new type of ß Receptor blocker, has a good antihypertensive effect. Many clinical trials have observed the clinical efficacy of arotinolol in the treatment of essential hypertension. However, so far, there has been no systematic evaluation on the efficacy and safety of arotinolol in the treatment of chronic heart failure. Objective: The purpose of this review was to systematically evaluate the clinical efficacy of arotinolol in patients with chronic heart failure. Methods: Randomized controlled trials (RCTs) of arotinolol in the treatment of chronic heart failure were retrieved from seven databases according to the Cochrane manual, including CNKI (China National Knowledge Infrastructure), Wan fang database, VIP database, PubMed, Sinomed, EMBASE, and the Cochrane Library databases. The main outcomes were the effective rate, left ventricular ejection fraction (LVEF), blood pressure, heart rate, cardiac index, stroke volume (SV), brain natriuretic peptide (BNP), hypersensitive C-reactive protein (Hs-CRP), left ventricular end diastolic volume (LVEDV), left ventricular end diastolic diameter (LVEDD), and adverse events (AEs). Results: A total of 17 trials met the qualification criteria, which included 1,717 patients with heart failure. Most trials had uncertain risks in terms of random sequence generation, allocation hiding, patient loss, and result evaluation. Meta analysis showed that arotinolol significantly improved the treatment efficiency of patients with heart failure (standardized mean difference (SMD) = 4.07, 95% confidence interval (CI) [2.89, 5.72], p = 0.00, I 2 = 0), LVEF (SMD = 1.59, 95% CI [0.99, 2.19], p = 0.000 0, I 2 = 95.8%), cardiac index (SMD = 0.32, 95% CI [0.11, 0.53], p = 0.03), I 2 = 0), SV (SMD = 2.00, 95% CI [1.57, 2.34], p = 0.000, I 2 = 64.2%), lower BNP (SMD = -0.804, 95% CI [-0.97, -0.64], p = 0.000, I 2 = 94.4%), and LVEDV (SMD = -0.25, 95% CI [-0.45, -0.05], p = 0.015, I 2 = 0). There was no statistical significance for blood pressure (SMDsystolic pressure = -0.09, 95% CI [-0.69, 0.51], p = 0.775, I 2 systolic pressure = 90.2%; SMDdiastolic pressure = -0.16, 95% CI [-0.79, 0.48], P = 0.632, I 2 diastolic pressure = 91.2%), heart rate (SMD = -0.12, 95% CI [-1.00, 0.75], P = 0.787, I 2 = 96.1%), Hs-CRP (SMD = -1.52, 95% CI [-3.43, 0.40], P = 0.121, I 2 = 98.3%), and LVEDD (SMD = -0.07, 95% CI [-0.90, 0.76], P = 0.870, I 2 = 96.5%). Conclusion: Arotinolol can safely and effectively improve the effective rate of patients with chronic heart failure, increase LVEF, increase CI and SV, and reduce BNP and LVEDV. However, because of the low overall quality of the included randomized controlled trials, these findings need to be considered carefully. More high-quality randomized controlled trials are needed for further verification, to provide a more scientific basis for the safety and effectiveness of arotinolol in the clinical treatment of heart failure. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=371214], identifier [CRD:420223371214].
RESUMO
Background: Hepatocellular carcinoma (HCC) is a common abdominal cancer. The existing therapeutic approaches often fail to achieve satisfactory results. Pyroptosis, an inflammatory form of programmed cell death, provides new ideas for anticancer treatment. However, the roles of pyroptosis-related (PR) genes (PRGs) in HCC remain elusive. Methods: Differentially expressed genes (DEGs) (n = 22) were screened out using TCGA and GTEx databases. A novel PR risk signature was constructed through Lasso regression analysis. Its prognostic value was evaluated through a series of survival analyses and was tested in ICGC and GSE14520 cohorts. CIBERSORT, ssGSEA, and ESTIMATE methods were employed to determine the effects of the PR risk score on the tumor immune microenvironment (TIM). The TIDE scoring system, IMvigor210 cohort, GSE109211 dataset, and GSDC database were applied to explore the associations of the PR risk score with therapeutic effects. The biofunctions of WNK1 in hepatocellular cancer (HC) cells were confirmed through qPCR, colony formation, and Transwell assays. Results: Overall, 22 of 45 PRGs (48.9%) were abnormally expressed in HCC samples. Then, a PR risk signature consisting of eight PRGs was constructed. A high PR risk score led to an unfavorable prognosis. The PR risk score was identified as an independent prognostic factor of HCC and could increase the decision-making benefit of the traditional TNM model. In addition, we established a nomogram containing the clinical stage and PR risk score to predict the survival rates of HCC patients. The prognostic value of the PR model was successfully validated in ICGC and GSE14520 cohorts. Moreover, high PR risk conferred the decreased infiltration level of CD8+ T cells and weakened the activities of "cytolytic activity" pathways. As for therapeutic correlation, a high PR risk score seemed to imply a poor efficacy of PD-1/L1 inhibitors and sorafenib. Finally, the overexpression of WNK1 could promote the proliferation, migration, and invasion of HC cells. Conclusions: The PR risk score was closely related to the prognosis, antitumor immune process, therapeutic outcomes, and malignant progression of HCC. WNK1, the core regulator of pyroptosis, possesses pro-oncogenic abilities, showing promise as a novel treatment target.