ps//www.clinicaltrials.gov; Unique identifier NCT01835028.Acute promyelocytic leukemia (APL) patients carry in 27% of cases an activating mutation of the fms-like tyrosine kinase-3 (FLT3) gene internal tandem duplication (ITD) or tyrosine kinase domain (TKD) point mutation. The simultaneous presence of both types of mutations, so-called FLT3 dual mutations, has been reported in 2% of APL, but this circumstance has never been studied. We studied a cohort of 74 APL cases, performing an in-depth analysis of three FLT3 dual mutant cases. Nanopore sequencing (NS) allowed us to characterize their complex mutational profile, showing the occurrence of multiple activating FLT3 mutations on different alleles in the leukemic promyelocytes and suggesting a cumulative impact of these events on the constitutive activation of the FLT3 pathway in APL cells. NS approach not only sheds light on the FLT3 mutational complexity in APL, but may also be useful to better clarify the FLT3 mutations landscape in acute myeloid leukemia.Catechol-O-methyltransferase (COMT) methylates both endogenous and exogenous catechol compounds to inactive and safe metabolites. We first optimised conditions for a convenient and sensitive continuous fluorescence-based 6-O-methylation assay of esculetin, which we used for investigating the COMT activity in human, mouse, rat, dog, rabbit, and sheep liver cytosols and microsomes and in ten different rat tissues. Furthermore, we compared the inhibition potencies and mechanisms of two clinically used COMT inhibitors, entacapone and tolcapone, in these species. In most tissues, the COMT activity was at least three times higher in cytosol than in microsomes. In the rat, the highest COMT activity was found in the liver, followed by kidney, ileum, thymus, spleen, lung, pancreas, heart, brain, and finally, skeletal muscle. Entacapone and tolcapone were characterised as highly potent mixed type tight-binding inhibitors. The competitive inhibition type dominated over the uncompetitive inhibition with entacapone, whereas uncompetitive inhibition dominated with tolcapone. Rats, dogs, pigs, and sheep are high COMT activity species, in contrast to humans, mice, and rabbits; COMT activity is highest in the liver. Both entacapone and tolcapone are potent COMT inhibitors, but their inhibition mechanisms differ.Adenomyoepithelioma (AME) of the male breast is a rare tumor characterized by biphasic proliferation of gland epithelial cells and myoepithelial cells.  https://www.selleckchem.com/products/zotatifin.html  Though pleomorphic adenoma (PA) is also known to be an epithelial-myoepithelial tumor in the breast, and these tumors are considered to exist on the same spectrum by some authors, to the best of our knowledge, there have been no reports of a clear transition from AME to PA in the male breast. Therefore, the case of an 85-year-old man with AME with PA-like components is presented.Hereditary pancreatitis is a rare form of recurrent acute pancreatitis that typically has an onset in early adulthood. We report a rare case of hereditary pancreatitis in an individual with a serine protease inhibitor Kazal type 1 (SPINK1) mutation. Histologically the pancreas showed features of chronic pancreatitis with variable fibrosis, acinar destruction, and prominent inspissated secretions within the pancreatic ducts. Additionally, focal areas of low-grade pancreatic intraepithelial neoplasia (PanIN) were present. Although the histopathology of common gene mutations resulting in hereditary pancreatitis have been well described, the histopathology of pancreatitis secondary to SPINK1 mutation has been described in only one previous study.Pericytes facilitate vessel maturation and endothelial barrier functions closely related with the pathogenesis of organ damage from cardiovascular and cerebrovascular diseases such as hypertension. We used a computational-based strategy to first screen for differentially expressed genes and lncRNAs and characterized associations between lncRNAs of microvascular pericytes and hypertension. In total, 22 lncRNAs were upregulated and 46 were downregulated in the rats afflicted with spontaneous hypertension. Expression profiles for lncRNAs were significantly altered in the hypertension afflicted tissue samples and the transcripts have good potential for use as molecular targets to inhibit the progression of hypertension.Despite many improvements in its prevention and management, acute coronary syndrome (ACS) remains a major cause of morbidity and mortality in the developed world. Lipid management is an important part of secondary prevention after ACS, but many patients currently remain undertreated and do not attain guideline-recommended levels of low-density lipoprotein cholesterol reduction. This review details the current state of evidence on lipid management in patients presenting with ACS, provides directions for identification of patients who may benefit from early escalation of lipid-lowering therapy, and discusses novel lipid-lowering medication that is currently under investigation in clinical trials. Moreover, a treatment algorithm aimed at attaining guideline-recommended low-density lipoprotein cholesterol levels is proposed. Despite important advances in the initial treatment and secondary prevention of ACS, ≈20% of ACS survivors experience a subsequent ischemic cardiovascular event within 24 months, and 5-year mortality ranges from 19% to 22%. Knowledge of the current state of evidence-based lipid management after ACS is of paramount importance to improve outcomes after ACS.
  Microwave ablation (MWA) is a safe and effective locoregional ablation modality, but it is not clear whether the curative effect of MWA as to hepatocellular carcinoma (HCC) is comparable to that of surgical resection (SR). We aimed to compare the outcomes of MWA and SR for patients with HCC ranging from 3 to 5 cm.
 
  197 patients treated for HCC between 3 and 5 cm by MWA or SR were included from 2010 to 2017. Overall survival (OS), progression-free survival (PFS), complication and hospital stay of those patients were compared by using propensity score matching. The registration number of this clinical trial was ChiCTR2000033983.
 
  For patients with HCC between 3 and 5 cm, the 1-, 3-, and 5- years OS rates were 90.3%, 79.7%, and 65.5% in the MWA group, and 96.7%, 88.6%, and 71%% in the SR group, respectively (
   = 0.457). The 1-, 3- and 5- years PFS rates were 63.6%, 36.8% and 32.7% in the MWA group, and 74.2%, 41.9% and 35.5% in the SR group, respectively (
   = 0.397). The MWA group showed fewer complications (55% versus 78.