Survival outcome among patients with out-of-hospital cardiac arrest who received cardiopulmonary resuscitation in China: a systematic review and meta-analysis.

BACKGROUND: This study aimed to assess the survival outcomes among patients with out-of-hospital cardiac arrest (CA) who received cardiopulmonary resuscitation (CPR) in China. METHODS: Relevant studies, published between January 1, 2010 and September 5, 2022, were retrieved from databases, including EMBASE, PubMed, Cochrane Library, the China Biology Medicine disk, China National Knowledge Infrastructure, and Wanfang databases. We included clinical studies in which all patients were diagnosed with CA and underwent out-of-hospital CPR, and the outcome variables were at least one of the following: return of spontaneous circulation (ROSC), survival to admission, survival to hospital discharge, 1-month survival, achieved good neurological outcomes, and 1-year survival. Two investigators independently extracted the study data and assessed its quality using a modified Newcastle-Ottawa Scale tool. The data were pooled using random-effects models. RESULTS: Of the 3620 identified studies, 49 (63,378 patients) were included in the meta-analysis. The pooled ROSC rate was 9.0% (95% confidence interval [CI] 7.5-10.5%, I2 = 97%), the pooled survival to admission rate was 5.0% (95% CI 2.7-8.0%, I2 = 98%), and the pooled survival to discharge rate was 1.8% (95% CI 1.2-2.5%, I2 = 95%). Additionally, the ROSC rate of patients with bystander CPR was significantly higher than that of those without bystander CPR, and the pooled odds ratio (OR) was 7.92 (95% CI 4.32-14.53, I2 = 85%). The ROSC rate of participants who started CPR within 5 min was significantly higher than that of those who started CPR after 5 min, and the pooled OR was 5.92 (95% CI 1.92-18.26, I2 = 85%). The ROSC rate of participants with defibrillation was significantly higher than that of those without defibrillation, and the pooled OR was 8.52 (95% CI 3.72-19.52, I2 = 77%). CONCLUSION: The survival outcomes of out-of-hospital CPR in China are far below the world average. Therefore, the policy of providing automated external defibrillators (AEDs) in public places and strengthening CPR training for healthcare providers and public personnel should be encouraged and disseminated nationwide. Trial registration This study was registered in PROSPERO (CRD42022326165) on 29 April 2022.

Overexpressed long noncoding RNA CRNDE with distinct alternatively spliced isoforms in multiple cancers.

Alternative splicing is a tightly regulated process that contributes to cancer development. CRNDE is a long noncoding RNA with alternative splicing and is implicated in the pathogenesis of several cancers. However, whether deregulated expression of CRNDE is common and which isoforms are mainly involved in cancers remain unclear. In this study, we report that CRNDE is aberrantly expressed in the majority of solid and hematopoietic malignancies. The investigation of CRNDE expression in normal samples revealed that CRNDE was expressed in a tissue- and cell-specific manner. Further comparison of CRNDE expression in 2938 patient samples from 15 solid and hematopoietic tumors showed that CRNDE was significantly overexpressed in 11 malignancies, including 3 reported and 8 unreported, and also implicated that the overexpressed isoforms differed in various cancer types. Furthermore, anti-cancer drugs could efficiently repress CRNDE overexpression in cancer cell lines and primary samples, and even had different impacts on the expression of CRNDE isoforms. Finally, experimental profiles of 12 alternatively spliced isoforms demonstrated that the spliced variant CRNDE-g was the most highly expressed isoform in multiple cancer types. Collectively, our results emphasize the cancer-associated feature of CRNDE and its spliced isoforms, and may provide promising targets for cancer diagnosis and therapy.

Profiling and functional analysis of circular RNAs in acute promyelocytic leukemia and their dynamic regulation during all-trans retinoic acid treatment.

Circular RNAs (circRNAs) are a novel class of powerful regulators in gene expression and participate in the pathogenesis of many diseases, including cancer. However, little is known about the roles of circRNAs in the development and treatment of acute promyelocytic leukemia (APL). Here we report the expression profiling and function of circRNAs in APL, including their dynamic regulation during all-trans retinoic acid (ATRA)-induced differentiation. We performed two independent ribosomal RNA-minus RNA-sequencing (Ribo-minus RNA-seq) experiments with and without RNase R treatment on APL patient-derived NB4 cells and identified a total of 4313 circRNAs, including 1098 newly identified circRNAs. Detailed analysis showed that circRNAs expressed in APL cells were mostly exon-derived, not by-products during splicing, and could be distinguished from hematopoietic stem cells, neutrophils and lymphocytes. The true presence and stability of circRNAs were verified both in NB4 cells and primary APL patient samples. Moreover, we conducted a time-series analysis of circRNAs on ATRA-treated NB4 cells and uncovered 508 circRNAs with dynamic expression during ATRA treatment, including 246 upregulated and 262 downregulated. Further evidence demonstrated that the majority of circRNAs were regulated independently of their host linear mRNAs. Detailed functional experiments demonstrated that circ-HIPK2, one of the differentially expressed circRNAs, significantly influenced ATRA-induced differentiation of APL cells. Further mechanistic studies revealed that circ-HIPK2 was located in cytoplasm and served as a sponge for differentiation-associated miR-124-3p. Finally, circ-HIPK2 expression in APL patients was significantly lower than that in normal peripheral mononuclear cells and other subtypes of AML, indicating its potential role as an APL biomarker. Our study indicates the biological functions of circRNAs in the development and treatment of APL, and provides a comprehensive circRNA resource for future studies.

Influence of body mass index on incidence and prognosis of acute myeloid leukemia and acute promyelocytic leukemia: A meta-analysis.

Previous studies have demonstrated an association between high body mass index (BMI) and acute myeloid leukemias (AML), particularly acute promyelocytic leukemia (APL). However, the effect of obesity and overweight on the incidence of AML is not supported by all studies, and the relationship between obesity and prognosis of AML and APL has not been established. Thus, we conducted a meta-analysis to determine the role of BMI on the risk and clinical outcome of AML, including APL. Twenty-six eligible studies enrolling 12,971 AML (including 866 APL) patients were retrieved and analyzed. Overweight and obesity was associated with an increased incidence of AML (relative risk [RR], 1.23; 95% confidence interval [CI], 1.12-1.35; P < 0.001). High BMI did not significantly affect overall survival (OS) (hazard ratio [HR], 0.97; 95% CI, 0.92-1.03; P = 0.323) or disease-free survival (HR, 0.98; 95% CI, 0.88-1.10; P = 0.755) in patients with non-APL AML. By contrast, APL patients with high BMI had shorter OS (HR, 1.77; 95% CI, 1.26-2.48; P = 0.001) and a higher risk of differentiation syndrome (HR, 1.53; 95% CI, 1.03-2.27, P = 0.04). Overall, our findings suggest that patients with overweight or obesity have a higher incidence of AML, and high BMI is a predictor of adverse clinical outcomes in APL.