Discovery of orally bioavailable ALK PROTACs based ceritinib against ALK positive cancers.

Anaplastic lymphoma kinase (ALK) fusion genes promote a variety of human malignancies. Although several ALK inhibitors have significantly improved disease prognosis in patients with ALK positive cancers, the persistent emergence of acquired drug-resistant mutations remain the major problem in clinic treatment. Adoption of new therapeutic strategies such as proteolysis targeting chimera (PROTAC) to overcome drug resistance in BTK/AR-related cancers have shown promising prospect.

Long-term sciatic nerve block led by a supramolecular arrangement of self-delivery local anesthetic nano systems.

Classical local anesthetics are unsuitable to treat regional pain lasting several days due to their limited duration and systemic toxicity. Self-delivery nano systems without excipients were designed for long-term sensory blocks. 1a self-assembled into different vehicles with different fractions of intermolecular π-π stacking, transported itself into nerve cells, and released single molecules slowly to achieve long-term duration for rats' sciatic nerve block for 11.

Behaviors of self-delivery lidocaine nano systems affected by intermolecular interaction.

Lidocaine salts self-assembled into different nano systems in water at a clinical dosage (2%, 0.2 mL) without excipient addition, and led to different sensory block durations and acute systemic toxicities, which were affected by the self-delivery and self-release behaviors of the salts . These differences were mainly caused by intermolecular π-π stacking under different conditions, which was proved by the unique supramolecular arrangement of gourd-shaped Janus particles.

An in-depth discussion of cholesteatoma, middle ear Inflammation, and langerhans cell histiocytosis of the temporal bone, based on diagnostic results.

Objective: This study aimed to conduct an in-depth investigation of the learning framework used for deriving diagnostic results of temporal bone diseases, including cholesteatoma and Langerhans cell histiocytosis (LCH). In addition, middle ear inflammation (MEI) was diagnosed by CT scanning of the temporal bone in pediatric patients.

Design: A total of 119 patients were included in this retrospective study; among them, 40 patients had MEI, 38 patients had histology-proven cholesteatoma, and 41 patients had histology-proven LCH of the temporal bone.

[Comparison of the Early Efficacy and Serious Adverse Events between CCCG-ALL 2015 and CCLG-ALL 2008 in the Treatment of Pediatric Patients with Acute Lymphoblastic Leukemia].

Objective: To evaluate the early efficacy and serious adverse events (SAE) related to chemotherapy of different protocols in the treatment of pediatric patients with acute lymphoblastic leukemia (ALL), so as to improve the overall survival rate.

Methods: A comparison of the early efficacy and SAE was performed between pediatric patients treated with Chinese Children Cancer Group-ALL 2015 (CCCG-ALL 2015) protocol from January 2019 to June 2020 and those treated with Chinese Children Leukemia Group-ALL 2008 (CCLG-ALL 2008) protocol from January 2017 to December 2018.

Results: The remission rate before consolidation chemotherapy between the two groups was not significantly different (P=0.

Retraction Notice to: Silencing Long Non-coding RNA LINC01224 Inhibits Hepatocellular Carcinoma Progression via MicroRNA-330-5p-Induced Inhibition of CHEK1.

[This retracts the article DOI: 10.1016/j.omtn.

CD8 T lymphocyte is a main source of interferon-gamma production in Takayasu's arteritis.

Interferon-gamma (IFN-γ) is a cytokine involved in the pathogenesis of Takayasu's arteritis (TAK). However, the source of IFN-γ in TAK patients is not fully clear. We aimed to investigate the source of IFN-γ in TAK.

The prognostic value of the peripheral blood cell counts changes during induction chemotherapy in Chinese patients with adult acute myeloid leukemia.

To investigate the prognostic value of the circulating peripheral blood cell counts changes in acute myeloid leukemia (AML) at different time points during induction chemotherapy.We retrospectively analyzed the clinical and laboratory data of 237 newly diagnosed AML patients admitted to Fujian Medical University Union Hospital from January 2011 to December 2014.1.

[Clinical Effect and Safety of CCLG-ALL 2008 (high risk group) Protocol in the Treatment of Childhood Mixed Phenotype Acute Leukemia].

Objective: To investigate the clinical effect and safety of Chinese Children's Leukemia Group (CCLG)-ALL 2008 (high risk group) protocol in the treatment with childhood Mixed phenotype acute leukemia (MPAL).

Methods: The clinical data of 15 new diagnosed patients with MPAL treated in our hospital from January 2013 to December 2017 were retrospectively analyzed, and received CCLG-ALL 2008 (high risk group) protocol chemotherapy.

Results: One patient gave up treatment after diagnosed, and 14 children with MPAL after induction remission chemotherapy, 3 patients gave up, and 5 patients received consolidation chemotherapy, and 6 patients received allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Relative transmissibility of shigellosis among male and female individuals: a modeling study in Hubei Province, China.

Background: Developing countries exhibit a high disease burden from shigellosis. Owing to the different incidences in males and females, this study aims to analyze the features involved in the transmission of shigellosis among male (subscript m) and female (subscript f) individuals using a newly developed sex-based model.

Methods: The data of reported shigellosis cases were collected from the China Information System for Disease Control and Prevention in Hubei Province from 2005 to 2017.

Contribution of Th2-like Treg cells to the pathogenesis of Takayasu's arteritis.

Objectives: Takayasu's arteritis (TAK) involves inflammatory vasculitis of large vessels and mainly affects the aorta and its major branches. Abnormal immunity may play a vital role in TAK pathogenesis. Regulatory T cells (Treg cells) are important for peripheral tolerance, but under certain conditions Treg cells can differentiate into Th-like cells that have lost immune suppressive function and promote the development of autoimmune diseases.

Silencing Long Non-coding RNA LINC01224 Inhibits Hepatocellular Carcinoma Progression via MicroRNA-330-5p-Induced Inhibition of CHEK1.

Hepatocellular carcinoma (HCC) accounts for approximately 85%-90% of primary liver cancers. Based on in silico analysis, differentially expressed long non-coding RNA (lncRNA) LINC01224 in HCC, the downstream microRNA (miRNA) miR-330-5p, and its target gene checkpoint kinase 1 (CHEK1) were selected as research subjects. Herein, this study was designed to evaluate their interaction effects on the malignant phenotypes of HCC cells.

Complete mitochondrial genome of the sharp-snouted pitviper (Reptilia, Viperidae).

The sharp-snouted pitviper, , belongs to the monotypic genus of the family Viperidae. It is one of the important species of snakes for its commercial and medicinal value. Complete mitochondrial genome sequence of the .

BMP2 secretion from hepatocellular carcinoma cell HepG2 enhances angiogenesis and tumor growth in endothelial cells via activation of the MAPK/p38 signaling pathway.

Background: Hepatocellular carcinoma (HCC) is one of the most common tumors globally, with varying prevalence based on endemic risk factors. Bone morphogenetic protein (BMP) exhibits a broad spectrum of biological activities in various tissues including angiogenesis. Here, this study aimed to investigate the mechanism of BMP2 in HCC by mediating the mitogen-activated protein kinase (MAPK)/p38 signaling pathway.

Luteolin decreases atherosclerosis in LDL receptor-deficient mice via a mechanism including decreasing AMPK-SIRT1 signaling in macrophages.

Lipid metabolism dysfunction and inflammatory infiltration into arterial walls are associated with the initiation and progression of atherosclerosis. Luteolin has been reported to possess anti-inflammatory actions and protect against tumor necrosis factor-α (TNF-α)-induced vascular inflammation, monocyte adhesion to endothelial cells and the formation of lipid-laden macrophages . However, the role of luteolin in atherosclerosis and the associated vascular inflammatory remains to be elucidated.

Association of Achilles tendon thickness and LDL-cholesterol levels in patients with hypercholesterolemia.

Background: Achilles tendons are the most common sites of tendon xanthomas that are commonly caused by disturbance of lipid metabolism. Achilles tendon thickening is the early characteristic of Achilles tendon xanthomas. The relationship between Achilles tendon thickness (ATT) and LDL-C levels, and risk factors of ATT in patients with hypercholesterolemia, have thus far been poorly documented.

Retrospective Analysis of a New Prognostic Score for Diffuse Large B-Cell Lymphoma Based on Interim Positron Emission Tomography-Computed Tomography.

Background: The International Prognostic Index (IPI) scoring system is the most widely used prognostic tool for diffuse large B-cell lymphoma (DLBCL); however, it fails to consistently identify patients with poor outcomes. This retrospective study was undertaken to confirm the clinical value of a new prognostic score and compare it with the IPI.

Methods: The aim of this single-center study was to confirm the clinical value of a new prognostic score and its association with various clinical features, disease progression, and death in 70 patients with DLBCL who had undergone at least 6 cycles of chemotherapy.

ETS1 and SP1 drive DHX15 expression in acute lymphoblastic leukaemia.

DHX15 plays a role in leukaemogenesis and leukaemia relapse. However, the mechanism underlying the transcriptional regulation of DHX15 in ALL has not been elucidated. Our present study aimed to explore the functional promoter region of DHX15 and to investigate the transcription factors controlling the transcription of this gene.

RKIP and peroxiredoxin 2 expression predicts the proliferative potential of gastric cancer stem cells.

Gastric cancer is associated with a high mortality rate, with the development of gastric cancer stem cells underlying this. Gastric cancer stem cells are responsible for tumor initiation, progression and recurrence. However, the link between gastric cancer and gastric cancer stem cells remains to be fully understood.

Treatment with Corticosteroid and/or Immunosuppressive Agents before Surgery can Effectively Improve the Surgical Outcome in Patients with Takayasu's Arteritis.

Objective: To analyze the clinical outcome of corticosteroid and/or immunosuppressive treatment preoperatively in patients with Takayasu's arteritis.

Patients And Methods: Forty-six patients with Takayasu's arteritis who received cardiovascular surgery between January 2010 and December 2015 in Beijing Anzhen Hospital were enrolled in this study. Their clinical characteristics, preoperative drug therapy, surgical treatment, and pathological examination results were retrospectively analyzed for the effect of drugs on outcome of the surgery.

Lentivirus-mediated RNA interference targeting inhibits cell growth and enhances cell differentiation of acute myeloid leukemia partially differentiated cells via inhibition of AKT and c-MYC.

Genetic heterogeneity is the basis of clinical heterogeneity among different subtypes of AML. We have successfully cloned a gene related to AML termed from a FAB-M2 patient's sample of a second largest AML pedigree. Then we revealed at least three splice variants, named as , and , and found miR181a1/b1 in the second intron of FAMLF gene family.

Mechanism of Formation of the Nonstandard Product in the Prenyltransferase Reaction of the G115T Mutant of FtmPT1: A Case of Reaction Dynamics Calling the Shots?

FtmPT1 is a fungal indole prenyltransferase that affords Tryprostatin B from Brevianamide F and dimethylallyl pyrophosphate; however, when a single residue in the active site is mutated (Gly115Thr), a novel five-membered ring compound is obtained as the major product with Tryprostatin B as the minor product. Herein, we describe detailed studies of the catalysis of the Gly115Thr mutant of FtmPT1 with a focus on the observed regioselectivity of the reaction. We employ one- and two-dimensional potential of mean force simulations to explore the catalytic mechanism, along with molecular dynamics simulations exploring the reaction dynamics of the prenyl transfer reaction.

17β-estradiol regulates the expression of apolipoprotein M through estrogen receptor α-specific binding motif in its promoter.

Background: We have previously demonstrated that estrogen could significantly enhance expression of apolipoprotein M (apoM), whereas the molecular basis of its mechanism is not fully elucidated yet. To further investigate the mechanism behind the estrogen induced up-regulation of apoM expression.

Results: Our results demonstrated either free 17β-estradiol (E2) or membrane-impermeable bovine serum albumin-conjugated E2 (E2-BSA) could modulate human apoM gene expression via the estrogen receptor alpha (ER-α) pathway in the HepG2 cells.