This compound also presented low cytotoxicity to mammalian cells with CC50 > 500 μM. Treatment of promastigote forms with different concentrations of PT4 resulted in ultrastructural alterations, such as plasma membrane wrinkling, shortening of cell body, increased cell volume and cell rupture. The molecular dynamic simulations showed that PT4 interacts with Lanosterol 14 α-demethylase from Leishmania, an essential enzyme of lipid synthesis pathway in this parasite. Our results demonstrated PT4 was effective against both species of Leishmania. PT4 caused a decrease of mitochondrial membrane potential and increased production of reactive oxygen species, which may lead to parasite death. Taken together, our results pointed PT4 as promissing therapeutic agent against CL.New series of hexahydroquinoline and fused quinoline derivatives were designed and synthesized. The thirty seven new compounds were screened for in vitro antitumor activity against HepG2, HCT-116 and MCF-7 cancer cells. Results indicated that compounds 2e, 2h, 5b, 5c, 6a, 7d and 9b have the strongest potency against the three cancer cells, and they were further screened for in vitro cytotoxicity against A431 and H1975 cancer cells, as well as WI38 and WISH normal cells. Results revealed that 7d potently inhibited the growth of H1975 cells harboring EGFRT790M mutation (IC50 = 1.32 ± 0.2 µM) over A431 cells overexpressing EGFRWT (IC50 = 4.96 ± 0.3 µM). Moreover, the seven compounds displayed low cytotoxicity against the tested normal cells. The seven potent antitumor compounds were examined for their ability to inhibit the activity of EGFRWT. The attained data manifested that 7d has remarkable EGFRWT inhibitory activity (IC50 = 0.083 ± 0.002 μM) compared to erlotinib (IC50 = 0.067 ± 0.002 μM). Compound 7d was further studied for its enzymatic inhibitory activity against other eight human kinases, and it displayed outstanding inhibitory activity against EGFRL858R and EGFRT790M mutants (IC50 = 0.053 ± 0.002, 0.026 ± 0.001 μM, respectively), as well as JAK3 (IC50 = 0.069 ± 0.003 μM). Analysis of cell cycle evidenced that 7d induces cell cycle arrest in G2/M and pre-G1 phases in the tested cancer cells. In addition, cancer cell death induced by 7d was proved to take place via apoptosis supported by elevated Bax/Bcl-2 ratio in the tested cancer cells. Moreover, docking results confirmed the good binding interactions of 7d with EGFRWT, EGFRL858R, EGFRT790M and JAK3, which came in agreement with the results of in vitro enzyme assay. Further, 7d is predicted to have good oral absorption, good drug-likeness properties and low toxicity risks in human. Deep venous thrombosis (DVT) is a common postoperative complication in patients undergoing major orthopaedic surgery of the lower limbs, such as total hip or knee replacement (THR, TKR). Routine pharmacological thromboprophylaxis with low-molecular-weight heparin (LMWH) or a direct oral anticoagulant agent is strongly recommended in this setting. THR and TKR as well as ankle arthrodesis are frequently performed in people with haemophilia (PWH) and chronic haemophilic arthropathy. Pharmacological thromboprophylaxis in this population remains controversial. We report the results of a single-centre prospective study initiated in 2002 evaluating by systematic Doppler ultrasound the incidence of subclinical DVT in consecutive PWH referred for major orthopaedic surgery and not receiving pharmacological thromboprophylaxis. We included 46 different PWH (39 Haemophilia A, 7 Haemophilia B, 27 severe, 15 moderate and 4 mild forms) undergoing 67 orthopaedic procedures. Most (89.5%) were performed with continuous infusion of clotting factor concentrates. Rehabilitation was usually started on day 1 post-op. No clinical DVT or pulmonary embolism was suspected. In total, there were 5 cases (3 severe, 1 moderate HA and 1 moderate HB) of subclinical DVT which were all distal. Two patients were treated with a short course (10-14days) of LMWH. The overall incidence of DVT was 7.5%. These data provide imaging-based evidence that the risk of DVT following major orthopaedic surgery among PWH is low. find more Identified DVTs were distal and resolved spontaneously in most cases. Systematic pharmacological thromboprophylaxis in this specific population is probably for most patients not required.These data provide imaging-based evidence that the risk of DVT following major orthopaedic surgery among PWH is low. Identified DVTs were distal and resolved spontaneously in most cases. Systematic pharmacological thromboprophylaxis in this specific population is probably for most patients not required. To improve evidence-based addiction care in acute care settings, many hospitals across North America are developing an inpatient addiction medicine consultation service (AMCS). St Paul's Hospital in Vancouver, Canada houses a large interdisciplinary AMCS. This study aimed to (1) describe the current model of clinical care and its evolution over time; (2) evaluate requests for an AMCS consultation over time; (3) highlight the established clinical training opportunities and educational curriculum and (4) provide some lessons learned. A retrospective observational analysis in an urban, academic hospital in Vancouver, Canada with a large interdisciplinary AMCS, studied from 2013 to 2018, among individuals who presented to hospital and had a substance use disorder. Data were collected using the hospital's electronic medical records. The primary outcome was number of AMCS consultations over time. In 2014 the hospital's AMCS was restructured into an academic, interdisciplinary consultation service. A 228% ine consultation service (AMCS), the AMCS saw a 228% increase in the number of consultation requests with more than half of requests originating from the emergency department. Approximately two-thirds of consultation requests were for opioid or stimulant use.Papillary thyroid cancer (PTC) is a major kind of thyroid cancer with increasing recurrence and metastasis. MiR-127 has been demonstrated to play roles in many cancers with dysregulation. However, the function of miR-127 is still unknown. This study aimed to explore a novel biomarker for the progression and prognosis of PTC. A set of 118 patients with PTC were collected from the Affiliated Hospital of Qingdao University. qRT-PCR was used to detect the expression of miR-127 in PTC tissues and cells. The association between miR-127 expression and the clinicopathological features of patients were evaluated by the χ2 test, and the prognostic value of miR-127 was evaluated by Kaplan-Meier analysis and Cox regression analysis. The effect of miR-127 on cell proliferation, migration, and invasion of PTC was analyzed by CCK-8 and transwell assay. miR-127 was found to be upregulated in PTC tissues and cells correlated with the TNM stage and poor prognosis of PTC patients. MiR-127 and the TNM stage were considered as two independent prognostic indicators for PTC.