Barriers and facilitators for improving oral anticoagulant medication adherence in lower extremity deep venous thrombosis patients after spinal surgery: A qualitative study using the COM-B model.

Background: Deep venous thrombosis (DVT) of the lower extremity causes a major disease burden globally. Currently, oral anticoagulant therapy is used as the first-line treatment of DVT, however, medication non-adherence remains a serious problem for postoperative spinal surgery patients whose DVT incidence is at a high level.

Aims: To explore barriers and facilitators affecting patient oral anticoagulant medication adherence, based on guidance using the COM-B model.

NR4A3 inhibits the tumor progression of hepatocellular carcinoma by inducing cell cycle G0/G1 phase arrest and upregulation of CDKN2AIP expression.

Nuclear receptor subfamily 4 group A member 3 (NR4A3) is a member of the orphan nuclear receptor superfamily, and exhibits transcription factor activity by binding to sequence-specific DNA. Considering that the specific mechanism by which NR4A3 regulates gene transcription in HCC (hepatocellular carcinoma) has not yet been elucidated, our study aimed to explore the transcriptional role of NR4A3 in regulating the target gene CDKN2AIP (CDKN2A interacting protein), which will suppress the development of HCC. Our data show that NR4A3 is downregulated in human HCC tissues, and that low expression of NR4A3 is correlated with poor prognosis, indicating that NR4A3 could act as a tumor suppressor gene in HCC.

TENT5A mediates the cancer-inhibiting effects of EGR1 by suppressing the protein stability of RPL35 in hepatocellular carcinoma.

Purpose: Terminal nucleotidyltransferase 5A (TENT5A), recently predicted as a non-canonical poly(A) polymerase, is critically involved in several human disorders including retinitis pigmentosa, cancer and obesity. However, the exact biological role of TENT5A in hepatocellular carcinoma (HCC) has not been elucidated.

Methods: The transcription level of TENT5A and clinical correlation were analyzed using the LIRI-JP cohort, the TCGA-LIHC cohort, and clinical tissue samples of HCC patients in our laboratory.

Identification and pre-clinical investigation of 3-O-cyclohexanecarbonyl-11-keto-β-boswellic acid as a drug for external use to treat psoriasis.

Background And Purpose: Psoriasis vulgaris is a refractory skin inflammatory disorder with 80% of the cases belonging to the mild-to-moderate type, which can be controlled by topical treatment. Nevertheless, the drugs for external use have not been upgraded for decades. We modified acetyl-11-keto-beta-boswellic acid (ABKA), a natural compound shown to treat psoriasis animal models, to improve efficacy and solubility for topical use.

Nurse and Patient Assessments of COVID-19 Care Quality in China: A Comparative Survey Study.

During the COVID-19 pandemic, the quality of nursing care was a concern due to nurses' overwhelming workload. A cross-sectional design was conducted to compare perceptions between nurses and patients about the quality of nursing care for COVID-19 patients and to explore factors associated with these perceptions. Data were collected during the COVID-19 pandemic from 17 March to 13 April 2020 in five hospitals in Wuhan, China.

FBXO9 Mediates the Cancer-Promoting Effects of ZNF143 by Degrading FBXW7 and Facilitates Drug Resistance in Hepatocellular Carcinoma.

F-box proteins are critical for malignancy because they control the turnover of key proteins that govern multiple cellular processes. F-box protein 9 (FBXO9) belongs to the F-box protein family and exhibits oncogenic properties in hematological malignancies. However, the function and molecular mechanism of FBXO9 in hepatocellular carcinoma (HCC) remain unclear.

STAT5A modulates CDYL2/SLC7A6 pathway to inhibit the proliferation and invasion of hepatocellular carcinoma by targeting to mTORC1.

Chromodomain Y-like 2 (CDYL2), as a member of CDY family known to be involved in spermatogenesis, has been reported to participate in breast cancer development recently, but its exact biological role in hepatocellular carcinoma (HCC) remains unclear. Here, we observed that CDYL2 was down-regulated in human primary HCC tissues and the low levels of CDYL2 expression were correlated with poor survival. Gain- and loss-of-function experiments showed that CDYL2 inhibited the proliferation and metastasis of HCC cells in vitro and in vivo.

The association between perceived hospital ethical climate and self-evaluated care quality for COVID-19 patients: the mediating role of ethical sensitivity among Chinese anti-pandemic nurses.

Background: The COVID-19 pandemic called for a new ethical climate in the designated hospitals and imposed challenges on care quality for anti-pandemic nurses. Less was known about whether hospital ethical climate and nurses' ethical sensitivity were associated with care quality. This study examined the association between the perceived hospital ethical climate and self-evaluated quality of care for COVID-19 patients among anti-pandemic nurses, and explored the mediating role of ethical sensitivity in this relationship.

Structure-activity relationship study of novel quinazoline-based 1,6-naphthyridinones as MET inhibitors with potent antitumor efficacy.

As a privileged scaffold, the quinazoline ring is widely used in the development of EGFR inhibitors, while few quinazoline-based MET inhibitors are reported. In our ongoing efforts to develop new MET-targeted anticancer drug candidates, a series of quinazoline-based 1,6-naphthyridinone derivatives were designed, synthesized, and evaluated for their biological activities. The preliminary SARs studies indicate that the quinazoline scaffold was also acceptable for the block A of class II MET inhibitors.

Evaluation of variation in D-dimer levels among COVID-19 and bacterial pneumonia: a retrospective analysis.

In the recent outbreak of novel coronavirus infection worldwide, the risk of thrombosis and bleeding should be concerned. We aimed to observe the dynamic changes of D-dimer levels during disease progression to evaluate their value for thrombosis. In this study, we report the clinical and laboratory results of 57 patients with confirmed COVID-19 pneumonia and 46 patients with confirmed community-acquired bacterial pneumonia (CAP).

MicroRNA-18a promotes cancer progression through SMG1 suppression and mTOR pathway activation in nasopharyngeal carcinoma.

miR-18a has been reported to be upregulated in nasopharyngeal carcinoma (NPC) tissues by microarray assays. However, the roles and the underlying mechanisms of miR-18a in NPC remain poorly understood. Here we demonstrated by real-time RT-PCR that miR-18a expression is upregulated in NPC tissues, and positively correlated with tumor size and TNM stage.

2,7-naphthyridinone-based MET kinase inhibitors: A promising novel scaffold for antitumor drug development.

As part of our effort to develop new molecular targeted antitumor drug, a novel 2,7-naphthyridone-based MET kinase inhibitor, 8-((4-((2-amino-3-chloropyridin-4-yl)oxy)- 3-fluorophenyl)amino)-2-(4-fluorophenyl)-2,7-naphthyridin-1(2H)-one (13f), was identified. Knowledge of the binding mode of BMS-777607 in MET led to the design of new inhibitors that utilize novel 2,7-naphthyridone scaffold to conformationally restrain the key pharmacophoric groups (block C). Detailed SAR studies resulted in the discovery of a new MET inhibitor 13f, displaying favorable in vitro potency and oral bioavailability.

miR-665 expression predicts poor survival and promotes tumor metastasis by targeting NR4A3 in breast cancer.

Cancer metastasis is the main cause of death in breast cancer (BC) patients. Therefore, prediction and treatment of metastasis is critical for enhancing the survival of BC patients. In this study, we aimed to identify biomarkers that can predict metastasis of BC and elucidate the underlying mechanism of the functional involvement of such markers in metastasis.

MicroRNA‑342‑3p suppresses proliferation and invasion of nasopharyngeal carcinoma cells by directly targeting Cdc42.

Deregulated microRNAs play an important role in the development and progression of various types of cancer. In our previous study, we observed that microRNA‑342‑3p (miR‑342‑3p) was one of the most markedly downregulated microRNAs in two nasopharyngeal carcinoma (NPC) cell lines compared to non‑neoplastic cells by using whole genome small RNA sequencing. In the present study, we confirmed that the expression of miR‑342‑3p was significantly reduced in NPC tissues compared with normal nasopharyngeal epithelial tissues.

Introduction of fluorine to phenyl group of 4-(2-pyrimidinylamino)benzamides leading to a series of potent hedgehog signaling pathway inhibitors.

In present study, a novel series of fluorine containing 4-(2-pyrimidinylamino)benzamide analogues were designed and synthesized. The hedgehog (Hh) signaling inhibitory activities for these compounds were evaluated by a luciferase reporter method. The preliminary SAR was discussed and many compounds showed potent Hh signaling inhibitory activities.

Identification of 4-(2-furanyl)pyrimidin-2-amines as Janus kinase 2 inhibitors.

Janus kinases inhibitor is considered to have therapeutic potential for the treatment of oncology and immune-inflammatory diseases. Two series of 4-(2-benzofuranyl)pyrimidin-2-amine and 4-(4,5,6,7-tetrahydrofuro[3,2-c]pyridin-2-yl)pyrimidin-2-amine derivatives have been designed and synthesized. Primary SAR studies resulted in the discovery of a novel class of 4,5,6,7-tetrahydrofuro[3,2-c]pyridine based JAK2 inhibitors with higher potency (IC of 0.

Calycosin induces apoptosis in colorectal cancer cells, through modulating the ERβ/MiR-95 and IGF-1R, PI3K/Akt signaling pathways.

Calycosin, the main component extractable from the herb Radix astragali, has been shown to inhibit cellular proliferation and induce apoptosis in several cancer cell lines, but the underlying mechanisms by the way in which this occurs remain unclear. In the present study, we aimed to determine the potential effects of calycosin on proliferation in colorectal cancer cells in vitro and in vivo and to elucidate the underlying molecular mechanisms of action. Colorectal cancer cell lines SW480 and LoVo and cervical cancer cell line HeLa were treated with various concentrations of calycosin or plus ER beta (ERβ) inhibitor PHTPP.

Synthesis and pharmacological evaluation of trifluoromethyl containing 4-(2-pyrimidinylamino)benzamides as Hedgehog signaling pathway inhibitors.

In present study, a series of novel containing trifluoromethyl 4-(2-pyrimidinylamino)benzamide derivatives were designed by the fluorine scan strategy. Their Hh signaling inhibitory activities were evaluated by Gli-luciferase reporter method. The comprehensive SAR was discussed and several derivatives were found to display more potent Hh signaling inhibitory activity than positive drug vismodegib.

Synthesis and biological evaluation of novel 7-substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amines as potent Bruton's tyrosine kinase (BTK) inhibitors.

A series of novel 7-substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amines as potent BTK inhibitors were designed, synthesized and evaluated. These thieno[3,2-c]pyridin-4-amine derivatives displayed variant inhibitory activities against BTK in vitro. Among these, 7-pyrazol-4-yl substituted 3-(4-phenoxyphenyl)thieno[3,2-c]pyridin-4-amine subseries showed high BTK inhibition and several compounds displayed superior BTK inhibitory activity.

Discovery of thieno[3,2-c]pyridin-4-amines as novel Bruton's tyrosine kinase (BTK) inhibitors.

A novel series of BTK inhibitors bearing thieno[3,2-c]pyridin-4-amine framework as the core scaffold were designed, synthesized and well characterized. In this paper, twenty one compounds displayed variant inhibitory activities against BTK in vitro, and compound 14 g showed the most potent inhibitory activity against BTK enzyme, with the IC50 value of 12.8 nM.

Calycosin induces apoptosis by the regulation of ERβ/miR-17 signaling pathway in human colorectal cancer cells.

Prior studies have suggested that a high intake of isoflavonoids is associated with a protective effect against hormone-related cancers, such as colorectal cancer (CRC). Calycosin, a main component of isoflavones, has been shown to suppress the growth of hormone-dependent tumors through an ERβ-mediated signaling pathway. However, the effects of calycosin on CRC remain unclear.

Pyrrolo[2,3-b]pyridine derivatives as potent Bruton's tyrosine kinase inhibitors.

A series of pyrrolo[2,3-b]pyridine-based derivatives were designed as potent Bruton's tyrosine kinase (BTK) inhibitors by using a scaffold-hopping strategy. Structure-activity relationship studies identified five compounds (3n, 3p, 3q, 3r, and 3s) with IC50 of less than 10nM in BTK enzyme assay and five compounds (3m, 3n, 3o, 3p, and 3t) with IC50 of less than 20 nM in Ramos cell assay. As one of the most potent inhibitors, compound 3p exhibited superior activity to that of compound 1 (RN486) and pyrrolo[2,3-d]pyrimidine derivative 2 in both BTK enzymatic (IC50=6.

Discovery of novel Bruton's tyrosine kinase (BTK) inhibitors bearing a pyrrolo[2,3-d]pyrimidine scaffold.

A series of novel reversible BTK inhibitors was designed based on the structure of the recently reported preclinical drug RN486. Knowledge of the binding mode of RN486 led to the design of new inhibitors that utilized pyrrolo[2,3-d]pyrimidine to conformationally restrain key pharmacophoric groups within the molecule. Comprehensive SAR was disclosed and the most promising compound 4x displayed superior activity both in BTK enzyme (IC50=4.

Design, synthesis and evaluation of novel 5-phenylpyridin-2(1H)-one derivatives as potent reversible Bruton's tyrosine kinase inhibitors.

A series of novel reversible Btk inhibitors has been designed based on the structure of the recently reported preclinical drug RN486. The synthesis and SAR of these compounds are described. Among these derivatives, compound 16b was identified to be a potent and orally available reversible agent with satisfactory Btk enzymatic and cellular inhibition in vitro, as well as favorable PK properties and inhibition of arthritis in vivo.