Discovery of pyridine-based derivatives as FLT3 inhibitors for the treatment of acute myeloid leukemia.

FMS-like tyrosine receptor kinase 3 (FLT3) mutations, the most common genetic alterations found in acute myeloid leukemia (AML) patients, have been pursued as an ideal drug discovery target for the AML therapy. Taking compound 2 as lead, a series of pyridine derivatives bearing 1,2,3-triazole moiety were rationally designed and synthesized. The bioassays confirmed that these derivatives exerted potent antileukemia effects, and compound 12y was found to be the most potent one.

Gut microbiota's role in high-altitude cognitive impairment: the therapeutic potential of Clostridium sp. supplementation.

Prolonged exposure to high-altitude environments may increase the risk of cognitive decline in young migrants. Recent studies suggest that hypobaric hypoxia-induced alterations in gut microbial composition could partly contribute to this risk. However, the absence of direct evidence from cohort studies and an unclear mechanism hinder intervention development based on this hypothesis.

JAG1 mediates apoptosis in herpes simplex keratitis by suppressing autophagy via ROS/JAG1/NOTCH1/pULK1 signaling pathway.

Herpes simplex keratitis (HSK), an ocular disease resulted from herpes simplex virus type 1 (HSV-1) infection, leads to the majority of infectious corneal blindness worldwide. The apoptosis of corneal epithelial cells (CECs) resulted from HSV-1 disrupts the epithelial barrier and exacerbates the infection; however, there is no definitive cure for HSK. Jagged1 (JAG1), one of the primary functional ligands for NOTCH receptors, plays a crucial role in regulating apoptosis and autophagy; however, its role in HSK is unclear.

Case Report: Treatment of a complex hand disfigurement injury by fully shaped reconstruction of a severed finger combined with ectopic banking.

One of the primary challenges in hand microsurgical reconstruction lies in addressing severe hand injuries, particularly those involving multiple finger amputations, as autologous replantation might not fully restore hand functionality. In such scenarios, fully shaped reconstruction of a severed finger combined with Ectopic banking could yield superior reconstructive outcomes and enhance the amputated limb's function. This case report presents a unique approach that combines ectopic replantation of an amputated finger with interphalangeal reconstruction methods to restore both the form and function of the hand.

The relationship between blood lipids and endometriosis: a cross-sectional study from NHANES (1999-2006) and a bidirectional Mendelian randomization study.

Objective: Observational studies suggest a link between blood lipid levels and endometriosis risk, but clinical evidence is limited and causality has not been established. This study aims to clarify this relationship using NHANES data (1999-2006) and bidirectional Mendelian Randomization (MR) analysis.

Methods: We analyzed NHANES data to explore the relationship between blood lipids and endometriosis risk using multivariable logistic regression, nonlinear testing, and trend analysis.

[Integrated evidence chain: a new strategy and methodology for effectiveness e valuation of traditional Chinese medicines].

The evaluation of the effectiveness of traditional Chinese medicine(TCM) has long been a "bottleneck" issue that restricts the healthy development and internationalization of TCM. This article systematically analyzes the differences in diagnostic and treatment principles, material composition, new drug development pathways, efficacy cognition, and evaluation methodology between Chinese and Western medicine from the underlying logic of medical perspective. On this basis, it integrates the evidence elements of clinical experience, experimental research, and clinical trials, and for the first time proposes and establishes a new strategy and methodology for the evaluation of the effectiveness of TCM: the integrated evidence chain-based effectiveness evaluation of traditional Chinese medicine(iEC-Eff), forming an integrated evaluation and confirmation model of "clinical experience-experimental research-clinical trial" for the effectiveness of TCM.

Early antiviral use and supplemental oxygen decrease the risk of secondary bacterial infections: a multi-centre, nested, case-control study.

Background: The purpose of this study was to evaluate the treatment strategies that dictate the host susceptibility to secondary bacterial infections during coronavirus disease 2019 (COVID-19).

Methods: This nested, case-control study was conducted in three general hospitals in China between 1 December 2022 and 1 March 2023. A total of 456 confirmed COVID-19 patients matched 1:2 (152 cases and 304 controls) based on age, sex, disease severity and age-adjusted Charlson Comorbidity Index (aCCI) using propensity-score matching (PSM) were included.

Laparoscopic hepatectomy versus microwave ablation for multifocal 3-5 cm hepatocellular carcinoma: a multi-centre, real-world study.

Background: Researches comparing laparoscopic liver resection (LLR) with microwave ablation (MWA) for 3-5 cm multifocal hepatocellular carcinoma (MFHCC) are rare.

Materials And Methods: From 2008 to 2019, 666 intrahepatic tumours in 289 patients from 12 tertiary medical centres in China were included in this retrospective study. Propensity score matching (PSM) was performed to balance variables between the two treatment groups over time frames 2008-2019 and 2013-2019 to observe the potential impact of advancements in intervention techniques on overall survival (OS), disease-free progression (DFS) of patients.

Neovascularization restructuring patterns in diabetic patients with coronary in stent restenosis: an in-vivo optical coherence tomography study.

Patients with diabetes mellitus (DM) have an increased risk of in stent restenosis (ISR). Neovascularization (NV) is considered as a unique pathophysiology factor of ISR in diabetic patients. However, the restructuring patterns of in vivo human coronary NV and their relationship with ISR, especially in diabetic patients remain unclear.

Clinical Study of Limosilactobacillus reuteri for the Treatment of Children with Chronic Tic Disorders/Tourette Syndrome: A Mid-Term Efficacy Evaluation.

Introduction: Gut microbiota plays an important role in tic disorders (TDs); however, clinical research on probiotics for chronic TDs treatment is lacking. We aimed to investigate the effectiveness of probiotics, hypothesizing that their clinical efficacy is comparable to that of clonidine in treating chronic TDs.

Methods: Patients were randomly assigned to receive either Limosilactobacillus reuteri or clonidine transdermal patch treatment for 8 weeks while maintaining their existing treatment.

Fluorinated Coumarin Derivatives as Selective PET Tracer for MAO-B Imaging.

Monoamine oxidase-B (MAO-B), predominantly exists on the outer mitochondrial membrane of astrocytes, serves as a crucial biomarker for reactive astrocytes during neuroinflammatory responses and various neurodegenerative diseases. In this study, we synthesized a series of fluorinated coumarin derivatives and evaluated their structure-activity relationship and subtype selectivity for MAO-B. Following this, the preclinical bioevaluation containing positron emission tomography (PET) imaging and autoradiography studies led to the identification of the novel PET tracer, [F], which demonstrated high affinity for MAO-B (IC = 0.

Adjuvant sorafenib for hepatocellular carcinoma after radiofrequency ablation versus radiofrequency ablation: analysis of its efficacy and safety.

Objectives: For the treatment of early hepatocellular carcinoma, we compared the efficacy and safety of radiofrequency ablation (RFA) alone and radiofrequency ablation combined with sorafenib (RFA+Sor).

Methods: A total of 164 patients with early HCC were included in the study. There were 87 patients who underwent RFA alone, and 77 patients who underwent RFA+Sor treatment.

Umbilical cord-derived mesenchymal stem cells preferentially modulate macrophages to alleviate pulmonary fibrosis.

Background: Idiopathic Pulmonary Fibrosis (IPF) is a type of interstitial lung disease characterized by chronic inflammation due to persistent lung damage. Mesenchymal stem cells (MSCs), including those derived from the umbilical cord (UCMSCs) and placenta (PLMSCs), have been utilized in clinical trials for IPF treatment. However, the varying therapeutic effectiveness between these two MSC types remains unclear.

Investigating the causal relationship between immune factors and ankylosing spondylitis: insights from a Mendelian Randomization study.

Background: Despite previous studies indicating a close relationship between immune system and ankylosing spondylitis (AS), the causal relationship between them remains unclear.

Methods: Genome-wide association data were utilized to explore the causal link between 731 immune cells and AS using a bidirectional two-sample MR approach. The data included immune cell data from Orrù et al.

Knowledge, attitude and practice toward fibromyalgia among fibromyalgia patients: A web-based cross-sectional study in China.

Background: This study aimed to explore the knowledge, attitude and practice (KAP) of fibromyalgia patients toward fibromyalgia.

Methods: This web-based cross-sectional study was conducted in China between February and March 2023 among fibromyalgia patients using a self-administered questionnaire.

Results: A total of 401 valid questionnaires were enrolled, including 326 (81.

The additive interaction of healthy lifestyles and genetic susceptibility on colorectal cancer risk in prediabetes: a large population-based prospective cohort study.

Objective: We aimed to investigate the interrelationships among polygenic risk scores (PRS), healthy lifestyle factors (HLFs), and colorectal cancer (CRC) risk in individuals with prediabetes. To investigate whether adherence to HLFs influence CRC risk in those with elevated PRS within this specific population.

Methods: Data from 22,408 prediabetes participants without CRC at baseline were analyzed from the UK Biobank.

Acute kidney injury in elderly patients receiving invasive mechanical ventilation: early versus late onset.

Background: Acute kidney injury (AKI) is a severe complication in critical patients receiving invasive mechanical ventilation (MV). However, AKI which occurs in the first 48 h after MV (early AKI) and thus likely associated with the MV settings is probably different from AKI occurring following 48 h (late AKI). This study is aimed at exploring the incidence of early and late AKI in elderly patients receiving MV and identifying their different risk factors and outcomes.

Development and validation of intravoxel incoherent motion diffusion weighted imaging-based model for preoperative distinguishing nuclear grade and survival of clear cell renal cell carcinoma complicated with venous tumor thrombus.

Objective: To assess the utility of multiparametric MRI and clinical indicators in distinguishing nuclear grade and survival of clear cell renal cell carcinoma (ccRCC) complicated with venous tumor thrombus (VTT).

Materials And Methods: This study included 105 and 27 patients in the training and test sets, respectively. Preoperative MRI, including intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), was performed.

Developing the new diagnostic model by integrating bioinformatics and machine learning for osteoarthritis.

Background: Osteoarthritis (OA) is a common cause of disability among the elderly, profoundly affecting quality of life. This study aims to leverage bioinformatics and machine learning to develop an artificial neural network (ANN) model for diagnosing OA, providing new avenues for early diagnosis and treatment.

Methods: From the Gene Expression Omnibus (GEO) database, we first obtained OA synovial tissue microarray datasets.

[A comparative study of dynamic versus static rehabilitation protocols after acute Achilles tendon rupture repair with channel assisted minimally invasive repair technique].

Objective: To explore the difference in effectiveness between a dynamic rehabilitation protocol and a traditional static rehabilitation protocol after the treatment of acute Achilles tendon rupture with channel assisted minimally invasive repair (CAMIR) technique through a prospective comparative trial, aiming to provide a reference for clinically selecting a feasible treatment regimen.

Methods: Patients with acute Achilles tendon rupture admitted between June 2021 and June 2022 were included in the study, with 60 patients meeting the selection criteria. They were randomly divided into a dynamic rehabilitation group ( =30) and a static rehabilitation group ( =30) using a computer-generated random number method.

[A comparative study of mid- and long-term effectiveness of patellar resurfacing or non-resurfacing in primary total knee arthroplasty].

Objective: To compare the mid- and long-term effectiveness of patellar resurfacing versus non-resurfacing in primary total knee arthroplasty (TKA).

Methods: Twenty-six patients who underwent bilateral TKA between March 2013 and September 2015 were selected as the study subjects. One side was randomly chosen for patellar resurfacing (resurfacing group), and the other side was not (control group).

Repeated low-intensity noise exposure exacerbates age-related hearing loss via RAGE signaling pathway.

Repeated low-intensity noise exposure is prevalent in industrialized societies. It has long been considered risk-free until recent evidence suggests that the temporary threshold shift (TTS) induced by such exposure might be a high-risk factor for hearing loss. This study was conducted to further investigate the manner in which repeated low-intensity noise exposure contributed to hearing damage.

A nomogram model for predicting advanced liver fibrosis in patients with hepatitis B: A multicenter study.

Background: Biopsy is the gold standard method for diagnosing liver fibrosis. FibroScan is a non-invasive method of diagnosing liver fibrosis, but it still faces some limitations. This study aimed to establish a nomogram model and identify patients at high risk of advanced liver fibrosis associated with hepatitis B infection.

Metabolomics based early warning model for acute kidney injury risk in patients exposed to diquat.

Acute kidney injury (AKI) is one of the most important indications of severe clinical symptoms in patients with diquat poisoning and is closely related to poor prognosis. However, current studies have rarely focused on early warnings of diquat-related AKI, which is not conducive to the treatment of patients with early clinical diquat poisoning. In this study, untargeted plasma metabolomics was employed to reveal the differences between diquat-poisoned patients with and without AKI, as well as between patients and healthy volunteers.