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These results are consistent with other recent reports and extend our understanding of YAP function in modulating fibrotic and inflammatory responses in the heart.Antimicrobial resistance seriously threatened human health, and new antimicrobial agents are desperately needed. As one of the largest classes of plant secondary metabolite, flavonoids can be widely found in various parts of the plant, and their antibacterial activities have been increasingly paid attention to. Based on the physicochemical parameters and antibacterial activities of sixty-six flavonoids reported, two regression equations between their ACD/LogP or LogD7.40 and their minimum inhibitory concentrations (MICs) to gram-positive bacteria were established with the correlation coefficients above 0.93, and then were verified by another sixty-eight flavonoids reported. From these two equations, the MICs of most flavonoids against gram-positive bacteria could be roughly calculated from their ACD/LogP or LogD7.40, and the minimum MIC was predicted as approximately 10.2 or 4.8 μM, more likely falls into the range from 2.6 to 10.2 μM, or from 1.2 to 4.8 μM. Simultaneously, both tendentiously concave regression curves indicated that the lipophilicity is a key factor for flavonoids against gram-positive bacteria. Combined with the literature analyses, the results also suggested that the cell membrane is the main site of flavonoids acting on gram-positive bacteria, and which likely involves the damage of phospholipid bilayers, the inhibition of the respiratory chain or the ATP synthesis, or some others.MicroRNAs have emerged as key regulators in vascular diseases and are involved in the formation of atherosclerotic lesions. However, the atherosclerotic-specific MicroRNAs and their functional roles in atherosclerosis are unclear. NX-5948 Here, we report that miR-378c protects against atherosclerosis by directly targeting Sterile Alpha Motif Domain Containing 1 (Samd1), a predicted transcriptional repressor. miR-378c was strikingly reduced in atherosclerotic plaques and blood of acute coronary syndrome (ACS) patients relative to healthy controls. Suppression of miR-378c promoted vascular smooth muscle cells (VSMCs) phenotypic transition during atherosclerosis. We also reported for the first time that Samd1 prolonged immobilization of LDL on the VSMCs, thus facilitated LDL oxidation and subsequently foam cell formation. Further, we found that Samd1 contains predicted DNA binding domain and directly binds to DNA regions as a transcriptional repressor. Together, we uncovered a novel mechanism whereby miR-378c-Samd1 circuit participates in two key elements of atherosclerosis, VSMCs phenotypic transition and LDL oxidation. Our results provided a better understanding of atherosclerosis pathophysiology and potential therapeutic management by targeting miR-378c-Samd1 circuit.We assessed the prevalence and factors related to the time to antiretroviral (ART) initiation among persons who entered HIV care and subsequently started ART in Croatia from 2005 to 2014. Included were patients ≥ 18 years, the follow-up ended on Dec/31/2017. 628 patients were included into the study 91.9% were men; median age was 36.1 (Q1-Q3 29.6-43.8) years. Rapid (within 7 days of diagnosis) ART initiation was observed in 21.8% patients, 49.8% initiated ART within 30 days, 21.7% and 28.5% had intermediate (31 days-1 year) and late initiation (> 1 year), respectively. Of 608 patients that achieved an undetectable viral load, 94% had a plasma HIV-1 RNA  less then  50 copies/ml at last measurement after a median follow-up of 5.2 years. On quantile regression analysis, calendar year of entry into care, and markers of more advanced HIV disease (higher viral load, lower CD4 cell count and clinical AIDS) were significantly associated with earlier ART initiation. Early ART was not related to a gap in care afterwards at all quantiles. In conclusion, a significant proportion of patients started ART early in Croatia in 2005-2014. Early ART initiation led to durable viral load suppression and was not associated with a subsequent gap in care.
This study aimed to evaluate the efficacy and safety of anlotinib as a third-line and subsequent treatment for patients with small cell lung cancer (SCLC).
We conducted this Phase 2 trial at 11 institutions in China. Patients with pathologically confirmed SCLC who failed at least two lines of chemotherapy were enrolled. Subjects were randomly assigned in a 21 ratio to receive either anlotinib 12 mg orally once daily for 14 days every 3 weeks or placebo. The primary endpoint was progression-free survival (PFS).
Between March 30, 2017 and June 8, 2018, a total of 82 and 38 patients were randomly assigned to receive anlotinib and placebo. The median PFS was significantly longer in the anlotinib group compared with the placebo group (4.1 months [95% confidence interval (CI), 2.8-4.2] vs 0.7 months [95% CI, 0.7-0.8]; hazard ratio (HR) 0.19 [95% CI, 0.12-0.32], p < 0.0001). Overall survival (OS) was significantly longer with anlotinib than placebo (7.3 months [95% CI, 6.1-10.3] vs 4.9 months [95% CI, 2.7-6.0]; HR 0.53 [95% CI, 0.34-0.81], p = 0.0029).
Anlotinib as a third-line or subsequent treatment for Chinese patients with SCLC showed improved PFS and OS than placebo with favourable safety profile.
ClinicalTrials.gov, number NCT03059797.
ClinicalTrials.gov, number NCT03059797.
We conducted a systematic review and meta-analysis of prospective studies to clarify the relation of fruit and vegetable consumption with incident breast cancer.
We searched systematically PubMed and EMBASE databases up to November 2020 to include prospective studies that reported the association of fruit and vegetable consumption with incidentbreast cancer. The pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated for the highest versus the lowest category of total fruit and vegetable,total fruitand total vegetable consumption, as well as fruit juice and subgroups of vegetables in relation to breast cancer incidence, using a random-effect model.
Total fruit and vegetable consumption was associated with lower overall (RR = 0.91, 95% CI = 0.87-0.95) and postmenopausal breast cancer risk (RR = 0.88, 95% CI = 0.79-0.99). Total fruit consumption was associated with lower overall (RR = 0.93, 95% CI = 0.88-0.99) and postmenopausal breast cancer risk (RR = 0.93, 95% CI = 0.87-0.99). Total fruit and vegetable intake were associated with 11% and 26% lower risk of oestrogen- and progesterone-receptor-positive (ER+/PR+) and -negative (ER-/PR-) breast cancer, respectively.