Small molecule inhibitor of the bromodomain and extraterminal domain (BET) family proteins is a promising option for cancer treatment. However, current BET inhibitors are limited by their potency or oral bioavailability. Here we report the discovery and characterization of NHWD-870, a BET inhibitor that is more potent than three major clinical stage BET inhibitors BMS-986158, OTX-015, and GSK-525762. NHWD-870 causes tumor shrinkage or significantly suppresses tumor growth in nine xenograft or syngeneic models. In addition to its ability to downregulate c-MYC and directly inhibit tumor cell proliferation, NHWD-870 blocks the proliferation of tumor associated macrophages (TAMs) through multiple mechanisms, partly by reducing the expression and secretion of macrophage colonystimulating factor CSF1 by tumor cells. NHWD-870 inhibits CSF1 expression through suppressing BRD4 and its target HIF1α. Taken together, these results reveal a mechanism by which BRD4 inhibition suppresses tumor growth, and support further development of NHWD-870 to treat solid tumors.

The psychometric properties of the C-MMAS-8 are satisfactory.

Cardiac telerehabilitation is a method that uses digital technologies to deliver cardiac rehabilitation from a distance. It has been shown to have benefits to improve patients' disease outcomes and quality of life, and further reduce readmission and adverse cardiac events. The outbreak of the coronavirus pandemic has brought considerable new challenges to cardiac rehabilitation, which foster cardiac telerehabilitation to be broadly applied. This transformation is associated with some difficulties that urgently need some innovations to search for the right path. Artificial intelligence, which has a high level of data mining and interpretation, may provide a potential solution. This review evaluates the current application and limitations of artificial intelligence in cardiac telerehabilitation and offers prospects.

Introduction Telehealth intervention has been proposed as a sustainable and innovative intervention approach to Parkinson’s disease (PD) patients, but there are still conflicting results in the literature about its effect. This study aimed to evaluate the efficacy of telehealth intervention for PD patients. Methods PubMed, EMBASE, CENTRAL and China National Knowledge Infrastructure (CNKI) were searched from the inception to June 2018 for randomized controlled trials (RCTs) and cohort studies, without language restrictions. When feasible, data were statistically pooled for meta-analysis using Review Manager 5.3. Otherwise, narrative summaries were used. Results Twenty-one studies were included. With respect to PD severity, compared with usual care, telehealth intervention was beneficial in lowering motor impairment of PD patients significantly (mean difference (MD) = –2.27, 95% confidence interval (95% CI) −4.25 to −0.29, p = 0.02), rather than mental status (MD = –0.98, 95% CI −2.61 to 0.65, p = 0.24), activities of daily living (MD = –1.51, 95% CI −4.91 to 1.89, p = 0.38) and motor complications (MD = –0.36, 95% CI −1.31 to 0.59, p = 0.46). Telehealth intervention did not lead to significant reduction in quality of life (standardized mean difference (SMD) = 0.04, 95% CI −0.20 to 0.28, p = 0.76), depression (SMD = –0.12, 95% CI −0.37 to 0.13, p = 0.34), cognition (MD = 0.37, 95% CI −0.34 to 1.09, p = 0.31) and balance (MD = 0.09, 95% CI −2.49 to 2.66, p = 0.95). Discussion Telehealth intervention is an effective option for individuals with PD to improve their motor impairment. Further well-designed studies are warranted to confirm our findings.