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Abstract Background Neuroblastoma (NBL) is the most common extra-cranial solid tumour in childhood, with prognosis ranging from spontaneous remission to high risk for rapid and fatal progression. Despite existing therapy approaches, the 5-year event-free survival (EFS) for patients with advanced NBL remains below 30%, emphasizing urgent necessary for novel therapeutic strategies. Studies have shown that epigenetic disorders play an essential role in the pathogenesis of NBL. However, the function and mechanism of N7-methylguanosine (m7G) methyltransferase in NBL remains unknown. Methods The expression levels of m7G tRNA methyltransferase Methyltransferase-like 1 (METTL1) were analyzed by querying the Gene Expression Omnibus (GEO) database and further confirmed by immunohistochemistry (IHC) assay. Kaplan-Meier, univariate and multivariate cox hazard analysis were performed to reveal the prognostic role of METTL1. Cell function assays were performed to evaluate how METTL1 works in proliferation, apoptosis and migration in cell lines and xenograft mouse models. The role of METTL1 on mRNA translation activity of NBL cells was measured using puromycin intake assay and polysome profiling assay. The m7G modified tRNAs were identified by tRNA reduction and cleavage sequencing (TRAC-seq). Ribosome nascent-chain complex-bound mRNA sequencing (RNC-seq) was utilized to identify the variation of gene translation efficiency (TE). Analyzed the codon frequency decoded by m7G tRNA to clarify the translation regulation and mechanism of m7G modification in NBL. Results This study found that METTL1 were significantly up-regulated in advanced NBL, which acted as an independent risk factor and predicted poor prognosis. Further in NBL cell lines and BALB/c-nu female mice, we found METTL1 played a crucial role in promoting NBL progression. Furthermore, m7G profiling and translation analysis revealed downregulation of METTL1 would inhibit puromycin intake efficiency of NBL cells, indicating that METTL1 did count crucially in regulation of NBL cell translation. With all tRNAs with m7G modification identified in NBL cells, knockdown of METTL1 would significantly reduce the levels of both m7G modification and m7G tRNAs expressions. Result of RNC-seq shew there were 339 overlapped genes with impaired translation in NBL cells upon METTL1 knockdown. Further analysis revealed these genes contained higher frequency of codons decoded by m7G-modified tRNAs and were enriched in oncogenic pathways. Conclusion This study revealed the critical role and mechanism of METTL1-mediated tRNA m7G modification in regulating NBL progression, providing new insights for developing therapeutic approaches for NBL patients.

Abstract Background The addition of consolidation chemotherapy to preoperative short-course radiotherapy during the prolonged interval between the completion of radiation and surgery in locally advanced rectal cancer (LARC) could enhance pathologic response and might act on potential micrometastasis. We performed this meta-analysis to evaluate whether short-course radiotherapy followed by consolidation chemotherapy (SCRT/CCT) could be a neoadjuvant treatment option compared with conventional long-course chemoradiotherapy (LCCRT). Methods We searched the PubMed, EMBASE, MEDLINE, and Cochrane Library databases. The primary endpoints were pathological outcomes, and the secondary endpoints included survival rate, sphincter preservation rate, R0 resection rate and toxicity. RevMan 5.3 was used to calculate pooled risk ratio (RRs) and 95% confidence intervals (CIs). Results A total of seven eligible studies and 1865 participants were included in this meta-analysis. Compared with the LCCRT, SCRT/CCT increased pathologic complete response (pCR) rate [RR = 1.74, 95% CI (1.41, 2.15), P

Abstract Background Although some studies have demonstrated that lncRNAs are dysregulated in hematopoietic malignancies and may regulate the progression of leukemia, the detailed mechanism underlying tumorigenesis is still unclear. This study aimed to investigate lncRNAs that are differentially expressed in childhood B-cell acute lymphoblastic leukemia (B-ALL) and T-cell acute lymphoblastic leukemia (T-ALL) and their potential roles in the progression of childhood ALL. Methods Microarrays were used to detect differentially expressed lncRNAs and mRNAs. Several aberrantly expressed lncRNAs were validated by qRT-PCR. Leukemia-free survival was analyzed using the Kaplan–Meier method with a log-rank test. The co-expression correlations of lncRNAs and mRNAs were determined by Spearman’s correlation coefficient. CCK-8 assays and flow cytometry were performed to measure cell proliferation and apoptosis. Results We revealed that many lncRNAs were abnormally expressed in B-ALL and T-ALL. LncRNA/mRNA co-expression and the gene locus network showed that dysregulated lncRNAs are involved in diverse cellular processes. We also assessed the diagnostic value of the differentially expressed lncRNAs and confirmed the optimal combination of TCONS_00026679, uc002ubt.1, ENST00000411904, and ENST00000547644 with an area under the curve of 0.9686 [95 % CI: 0.9369–1.000, P

Abstract Background The prevalence of hypertension is high and increasing in China in recent years. The treatment and control of hypertension calls for long-term management beyond hospital, which is hard to implement in traditional care settings. Integrated care combined with information technology can promote high-quality healthcare services across the life-course. However, few studies have applied a customized integrated care model in community-based hypertension management in China, catering to the emerging “three-manager” mode. This study aims to identify the effectiveness of a pathway-driven eHealth-based integrated model that implemented as a full-featured telehealth system to facilitate standardized management of hypertension in China. Methods The trial has been designed as a 1-year, non-blinded superiority trial with two parallel groups. A total of 402 hypertensive patients who meet the eligibility criteria will be recruited and randomized with a 1:1 allocation. All the participants will receive a mobile device for self-management, which is a part of our telehealth system. Participants in the control group will only use the device for BP measurement and receive regular follow-ups from care providers according to the guidelines. Participants in the intervention group will gain full access to the system and receive intervention based on the proposed model (a well-designed coordinated care pathway consisting of 9 tasks). Outcomes will be measured mainly on three occasions (at inclusion, at 6 months, and at 12 months). The primary outcome is mean change in systolic blood pressure over a 12-month period. Secondary outcomes include changes in diastolic blood pressure, biochemical indexes related to hypertension, lifestyles, self-management adherence, and hypertension awareness, as well as work efficiency of care providers. Discussion This study aims to investigate whether a pathway-driven eHealth-based integrated care model based on the “three-manager” mode will improve hypertension control in China. Success of the model would help improve the quality of present community-based management procedures and benefit more patients with uncontrolled hypertension. Trial registration Chinese Clinical Trial Registry ChiCTR1900027645 . Registered on November 22, 2019.