Repeatability and reproducibility comparisons of liver IVIM imaging with free-breathing or respiratory-triggered sequences.

For liver intravoxel incoherent motion (IVIM) data acquisition, respiratory-triggering (RT) MRI is commonly used, and there are strong motivations to shorten the scan duration. For the same scan duration, more b values or higher numbers of excitations can be allowed for free-breathing (FB) imaging than for RT. We studied whether FB can be used to replace RT when careful IVIM image acquisition and image processing are conducted. MRI data of 22 healthy participants were acquired using a 3.0 T scanner. Diffusion imaging was based on a single-shot spin-echo-type echo-planar sequence and 16 b values of 0, 2, 4, 7, 10, 15, 20, 30, 46, 60, 72, 100, 150, 200, 400, and 600 s/mm2 . Each subject attended two scan sessions with an interval of 10-20 days. For each scan session, a subject was scanned twice, first with RT and then with FB. The mean image acquisition time was 5.4 min for FB and 10.8 min for RT. IVIM parameters were calculated with bi-exponential model segmented fitting with a threshold b value of 60 s/mm2 , and fitting started from b = 2 s/mm2 . There was no statistically significant difference between IVIM parameters measured with FB imaging or RT imaging. Perfusion fraction ICC (intraclass correlation coefficient) for FB imaging and RT imaging in the same scan session was 0.824. For perfusion fraction, wSD (within-subject standard deviation), BA (Bland-Altman) difference, BA 95% limit, and ICC were 0.022, 0.0001, -0.0635~0.0637, and 0.687 for FB and 0.031, 0.0122, -0.0723~0.0967, and 0.611 for RT. For Dslow (×10-3  s/mm2 ), wSD, BA difference, BA 95% limit, and ICC were 0.057, 0.0268, -0.1258~0.1793, and 0.471 for FB and 0.073, -0.0078, -0.2170-0.2014, and <0.4 for RT. The Dfast coefficient of variation was 0.20 for FB imaging and 0.28 for RT imaging. All reproducibility indicators slightly favored FB imaging.

[The Risk and Survival Analysis of Multiple Malignancies in Hematologic Malignancy Patients: A Single Chinese Center Retrospective Study, 2009 through 2017].

OBJECTIVE: To explore the risk and location of multiple malignancies in patients with hematologic malignancies who were followed up for 9 years in Jiangsu Province Hospital and to evaluate the impact of the second primary malignancy on survival of patients. METHODS: The incidence and survival of multiple malignancies in 7 921 patients with hematologic malignancies from 2009 to 2017 were analyzed retrospectively. RESULTS: A total of 180 (2.3%, 180/7 921) patients developed second malignancy, of whom 58 patients were diagnosed with hematologic malignancies as the first primary malignancy, and 98 patients developed hematologic malignancies as second primary malignancy, and the other 24 cases were diagnosed with the second malignancy within 6 months after the first primary malignancy was diagnosed, which was difined as multiple malignancies occurring simultaneously. In 180 patients, 18 cases developed two hematologic malignancies successively, and 11 patients developed more than 3 primary cancers (among them, 2 female patients were diagnosed with 4 primary cancers). Patients with lymphoma and multiple myeloma (MM) as the second primary malignancy had poorer survival than patients with lymphoma and MM as the first primary malignancy. Patients with chronic myeloid leukemia as the second primary malignancy were also associated with inferior overall survival. CONCLUSION: In this study, 2.3% of hematologic malignancy patients had multiple mali-gnancies, lymphoma and MM as the second primary malignancy had poor survival.

An innovative role for luteolin as a natural quorum sensing inhibitor in Pseudomonas aeruginosa.

AIMS: The emergence of antibiotic tolerance was a tricky problem in the treatment of chronic Pseudomonas aeruginosa-infected cystic fibrosis and burn victims. The quorum sensing (QS) inhibitor may serve as a new tactic for the bacterial resistance by inhibiting the biofilm formation and the production of virulence factors. This study explored the potential of luteolin as a QS inhibitor against P. aeruginosa and the molecular mechanism involved. MAIN METHODS: Crystal violet staining, CLSM observation, and SEM analysis were carried out to assess the effect of luteolin on biofilm formation. The motility assays and the production of virulence factors were determined to evaluate the QS-inhibitory activity of luteolin. Acyl-homoserine lactone, RT-PCR, and molecular docking assays were conducted to explain its anti-QS mechanisms. KEY FINDINGS: The biofilm formation, the production of virulence factors, and the motility of P. aeruginosa could be efficiently inhibited by luteolin. Luteolin could also attenuate the accumulation of the QS-signaling molecules N-(3-oxododecanoyl)-L-homoserine lactone (OdDHL) and N-butanoyl-L-homoserine lactone (BHL) (P < 0.01) and downregulate the transcription levels of QS genes (lasR, lasI, rhlR, and rhlI) (P < 0.01). Molecular docking analysis indicated that luteolin had a greater docking affinity with LasR regulator protein compared with OdDHL. SIGNIFICANCE: This study is important as it reports the molecular mechanisms involved in the anti-biofilm formation activity of luteolin against P. aeruginosa. This study also indicated that luteolin could be helpful when used for the treatment of clinical drug-resistant infections of P. aeruginosa.

Inhibition of hsa_circ_0003489 shifts balance from autophagy to apoptosis and sensitizes multiple myeloma cells to bortezomib via miR-874-3p/HDAC1 axis.

BACKGROUND: Circular RNAs (circRNAs) crucially regulate tumor progression. In this study, we examined the functional roles and mechanisms of hsa_circ_0003489 in multiple myeloma (MM). METHODS: Upon altering the expressions of hsa_circ_0003489, miR-874-3p, and/or histone deacetylase 1 (HDAC1) in MM1.R cells and treating them with bortezomib (BTZ), cell viability was examined by CCK-8 assay; cell proliferation by Ki-67 immunofluorescence; apoptosis by TUNEL staining, flow cytometry, and western blot; and autophagy by electron microscopy and western blot. The interaction between hsa_circ_0003489 and miR-874-3p as well as that between miR-874-3p and HDAC1 was examined by expressional analysis, dual luciferase reporter assay, and RNA immunoprecipitation. The in vivo impacts of hsa_circ_0003489 on MM growth and sensitivity to BTZ were examined using an MM xenograft mouse model. RESULTS: Knocking down hsa_circ_0003489 significantly inhibited the viability, cell proliferation, and autophagy, while promoting the apoptosis of MM cells in vitro and MM xenograft in vivo. Suppressing hsa_circ_0003489 also further boosted the cytotoxic effects of BTZ in MM cells and reversed its promoting effect on autophagy. Mechanically, hsa_circ_0003489 acted as a sponge of miR-874-3p and positively regulated the expression of miR-874-3p target, HDAC1. MiR-874-3p and HDAC1 essentially mediated the effects of hsa_circ_0003489 on cell viability, proliferation, apoptosis, and autophagy. CONCLUSION: The hsa_circ_0003489/miR-874-3p/HDAC1 axis critically regulates the balance between apoptosis and autophagy. Silencing hsa_circ_0003489 sensitizes MM cells to BTZ by inhibiting autophagy and thus may boost the therapeutic effects of BTZ.