In a previous meta-analysis, it was demonstrated that the resting heart rate (RHR) is a potential risk factor for atrial fibrillation (AF). However, the results of that meta-analysis were conflicting, and the relationship between the RHR and AF is still not well established. In the current meta-analysis, our aim is to update evidence with a better statistical model. We searched the Cochrane Library, PubMed, and Embase databases for relevant studies and used a "one-stage approach" with a restricted cubic spline model to summarize the dose-specific relationships between the RHR and AF. Relative risk (RR) was used to measure the effects. In total, 10 studies were included, with a total of 18,630 cases of AF among 431,432 participants. In the dose-response analysis, there was evidence of a nonlinear association between the RHR and the risk of AF (nonlinearity, P < 0.0001), which exhibited a significant J-shaped association between the two factors. An RHR between 68 and 80 bpm had the lowest risk of AF. Among people who had RHR < 70 bpm, the summary RR was 1.09 per 10-RHR decrease (95% confidence interval [CI] = 1.06-1.12; P < 0.001). The results were similar for participants with RHR > 70 bpm (per 10 bpm increase) (RR = 1.06, 95% CI = 1.03-1.08; P < 0.001). Our dose-response metaanalysis revealed a significant J-shaped association between the RHR and AF. Both low RHR and high RHR were associated with an increased risk of AF compared with a modest RHR of 68-80 bpm.

Multiple myeloma (MM) accounts for over twenty percent of hematological cancer-related death worldwide. Long noncoding RNA (lncRNA) H19 is associated with multiple tumorigenesis and is increased in MM, but the underlying mechanism of H19 in MM is unclear. In this study, the expression of H19, microRNA 152-3p (miR-152-3p), and BRD4 in MM patients was evaluated by quantitative real-time PCR (qRT-PCR) and Western blotting. Colony formation and flow cytometry analysis were used to determine the effects of H19 and miR-152-3p on MM cell proliferation, apoptosis, and cell cycle. A luciferase reporter assay was conducted to confirm the interaction among H19, miR-152-3p, and BRD4. A nude mouse xenograft model was established, and the cell proliferation and apoptosis were evaluated by immunohistochemistry (IHC) staining and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling assay. We found that levels of H19 and BRD4 were upregulated and the expression of miR-152-3p was downregulated in MM patients. Dual luciferase reporter assay showed H19 targeted miR-152-3p to promote BRD4 expression. Knockdown of H19 repressed proliferation and enhanced apoptosis and cell cycle G1 arrest by upregulating miR-152-3p in MM cells. Furthermore, H19 knockdown suppressed the growth of xenograft tumor, reduced Ki-67 and BRD4 levels, and increased cell apoptosis in xenograft tumor tissues. Taking these results together, H19 knockdown suppresses MM tumorigenesis via inhibiting BRD4-mediated cell proliferation through targeting miR-152-3p, implying that H19 is a promising biomarker and drug target for MM.

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Long non-coding RNA (lncRNA) MALAT1 has been confirmed to function as an oncogene in various solid tumors. MALAT1 level has been shown to be upregulated in relapsed acute lymphoblastic leukemia (ALL) patients, but the mechanism is unclear. This study aims to investigate the functional roles and underlying mechanisms of MALAT1 in ALL. MALAT1 and miR-205 expression were assessed by real-time quantitative polymerase chain reaction (RT-qPCR). MTT assay and flow cytometry were performed to evaluate cell proliferation and apoptosis, respectively. Protein level of protein tyrosine kinase-7 (PTK7) was detected by Western blot assay. Dual luciferase reporter assay was conducted to confirm the binding of MALAT1 and miR-205, as well as miR-205 and PTK7. The levels of MALAT1 and PTK7 were upregulated in ALL samples. In contrast, miR-205 level was downregulated in ALL in ALL samples. Moreover, MALAT1 silencing or miR-205 overexpression restrained proliferation and promoted apoptosis of ALL cells. Mechanistically, MALAT1 sponged miR-205 to regulate PTK7 expression. In summary, MALAT1 affected ALL cell proliferation and apoptosis via regulating miR-205-PTK7 axis. Our results suggest that MALAT1-miR-205-PTK7 axis participates in the proliferation and apoptosis of ALL, which may provide a potential treatment target for ALL.

Background: Multiple myeloma (MM) is an incurable hematologic cancer, accompanied by excessive osteoclast formation and inflammatory cytokine secretion. The mechanisms by which bromodomain and extra-terminal domain (BET) protein inhibitor I-BET151 regulates osteoclast differentiation and inflammatory cytokine secretion in MM are largely unknown. Methods: The isolated peripheral blood mononuclear cells from normal or patients with MM were treated with receptor activator of NF-κB ligand (RANKL) and M-CSF to induce osteoclast differentiation. RAW 264.7 cells were treated with RANKL. I-BET151 was applied to investigate the effects of BRD4 inhibition on osteoclast formation and inflammatory cytokine secretion. Osteoclast formation was determined by tartrate-resistant acid phosphatase (TRACP) staining. The expression of osteoclast-specific genes TRACP, matrix metalloproteinase-9 (MMP-9), cathepsin K (Ctsk), and c-Src was tested using quantitative real-time PCR. And the level of inflammatory cytokines TNF-α, IL-1β, and IL-6 was assessed by ELISA. Tumor necrosis factor receptor-associated factor 6 (TRAF6), BRD4, nuclear and cytoplasm p65, IκB-α, nuclear factor of activated T cells cytoplasmic (NFATc1), and osteoprotegerin (OPG) expression were measured by Western blotting. RNAi technology was applied to knock down BET family member BRD4. Results: I-BET151 dose-dependently suppressed osteoclast formation, inhibited the levels of osteoclast-specific genes TRACP, MMP-9, Ctsk, and c-Src and inflammatory cytokines TNF-α, IL-1β, and IL-6 secretion in peripheral blood mononuclear cells and RAW 264.7. I-BET151 inhibited the protein levels of BRD4 and NFATc1, increased OPG expression, and suppressed IκB-α degradation and p65 nuclear translocation. Further, the effects of I-BET151 on osteoclast formation, osteoclast-specific genes expression, inflammatory cytokine secretion, and NF-κB inhibition were promoted by BRD4 knockdown. Conclusion: I-BET151 inhibits osteoclast formation and inflammatory cytokine secretion by targetting BRD4-mediated RANKL-NF-κB signal pathway and BRD4 inhibition might be beneficial for MM treatment.