First-in-human trial of SAR107375E, a novel small molecule anticoagulant with dual inhibition of factor Xa and factor IIa.

Background: SAR107375E is a direct dual inhibitor of both Factor Xa and Factor IIa and has shown potent anticoagulation activity in vitro and animals. This study evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of single ascending intravenous doses of SAR107375E in healthy Chinese adult subjects.

Methods: In this randomized, double-blind, placebo-controlled trial, 60 healthy Chinese adult subjects were administered intravenously single ascending doses (0.

The role and mechanisms of macrophage polarization and hepatocyte pyroptosis in acute liver failure.

Acute liver failure (ALF) is a severe liver disease caused by disruptions in the body's immune microenvironment. In the early stages of ALF, Kupffer cells (KCs) become depleted and recruit monocytes derived from the bone marrow or abdomen to replace the depleted macrophages entering the liver. These monocytes differentiate into mature macrophages, which are activated in the immune microenvironment of the liver and polarized to perform various functions.

Incidence and predictors of elevated postpartum alanine aminotransferase in chronic hepatitis B mothers: a prospective study protocol.

Background: The majority of HBeAg-positive mothers with chronic hepatitis B have high levels of viremia and inactive disease with normal alanine aminotransferase (ALT) during pregnancy. In addition, postpartum disease activation and ALT flare have been reported in the range of 15 - 35%. However, the current International Association Guidelines have not provided clear recommendations and a risk-stratified monitoring schedule.

TGF-β, EMT, and resistance to anti-cancer treatment.

Transforming growth factor-β (TGF-β) signaling regulates cell-specific programs involved in embryonic development, wound-healing, and immune homeostasis. Yet, during tumor progression, these TGF-β-mediated programs are altered, leading to epithelial cell plasticity and a reprogramming of epithelial cells into mesenchymal lineages through epithelial-to-mesenchymal transition (EMT), a critical developmental program in morphogenesis and organogenesis. These changes, in turn, lead to enhanced carcinoma cell invasion, metastasis, immune cell differentiation, immune evasion, and chemotherapy resistance.

Tacrolimus reverses pemphigus vulgaris serum-induced depletion of desmoglein in HaCaT cells via inhibition of heat shock protein 27 phosphorylation.

Background: Glucocorticoids are the first-line treatment for Pemphigus vulgaris (PV), but its serious side effects can be life-threatening for PV patients. Tacrolimus (FK506) has been reported to have an adjuvant treatment effect against PV. However, the mechanism underlying the inhibitory effect of FK506 on PV-IgG-induced acantholysis is unclear.

[A close contact of coronavirus disease 2019 with severe imported malaria: a case report].

This article presents a severe cerebral malaria patient in shock with a close contact of COVID-19 that was successfully cured in a negative pressure ward during the global pandemic of COVID-19. The patient experienced a sudden onset of high fever and coma in a designated isolation hotel after returning from Africa, and was transferred to a designated hospital. Following antimalarial therapy, blood pressure elevation, increase of blood volume, bedside hemodialysis, mechanical ventilation, plasma and platelet transfusions, the case gradual recovered.

Gli1 marks a sentinel muscle stem cell population for muscle regeneration.

Adult skeletal muscle regeneration is mainly driven by muscle stem cells (MuSCs), which are highly heterogeneous. Although recent studies have started to characterize the heterogeneity of MuSCs, whether a subset of cells with distinct exists within MuSCs remains unanswered. Here, we find that a population of MuSCs, marked by Gli1 expression, is required for muscle regeneration.

Brain tumor image segmentation based on improved FPN.

Purpose: Automatic segmentation of brain tumors by deep learning algorithm is one of the research hotspots in the field of medical image segmentation. An improved FPN network for brain tumor segmentation is proposed to improve the segmentation effect of brain tumor.

Materials And Methods: Aiming at the problem that the traditional full convolutional neural network (FCN) has weak processing ability, which leads to the loss of details in tumor segmentation, this paper proposes a brain tumor image segmentation method based on the improved feature pyramid networks (FPN) convolutional neural network.

Corrigendum: Use of autologous cord blood mononuclear cells infusion for the prevention of bronchopulmonary dysplasia in extremely preterm neonates: a study protocol for a placebo-controlled randomized multicenter trial [NCT03053076].

[This corrects the article DOI: 10.3389/fped.2020.

Three cases of scrub typhus with hemorrhage: a case report and literature review.

Scrub typhus (ST) is an acute focal infectious disease that is caused by . The Asia-Pacific region is an area of relatively high incidence. There is a high incidence in China, principally owing to the disease being endemic in the south of the country.

Evaluating the Effect of Artificial Liver Support on Acute-on-Chronic Liver Failure Using the Quantitative Difference Algorithm: Retrospective Study.

Background: Liver failure, including acute-on-chronic liver failure (ACLF), occurs mainly in young adults and is associated with high mortality and resource costs. The prognosis evaluation is a crucial part of the ACLF treatment process and should run through the entire diagnosis process. As a recently proposed novel algorithm, the quantitative difference (QD) algorithm holds promise for enhancing the prognosis evaluation of ACLF.

Mesenchymal Stem Cells-based Cell-free Therapy Targeting Neuroinflammation.

Emerging from several decades of extensive research, key genetic elements and biochemical mechanisms implicated in neuroinflammation have been delineated, contributing substantially to our understanding of neurodegenerative diseases (NDDs). In this minireview, we discuss data predominantly from the past three years, highlighting the pivotal roles and mechanisms of the two principal cell types implicated in neuroinflammation. The review also underscores the extended process of peripheral inflammation that predates symptomatic onset, the critical influence of neuroinflammation, and their dynamic interplay in the pathogenesis of NDDs.

Schizophrenia-Like Behaviors Arising from Dysregulated Proline Metabolism Are Associated with Altered Neuronal Morphology and Function in Mice with Hippocampal PRODH Deficiency.

Despite decades of research being conducted to understand what physiological deficits in the brain are an underlying basis of psychiatric diseases like schizophrenia, it has remained difficult to establish a direct causal relationship between neuronal dysfunction and specific behavioral phenotypes. Moreover, it remains unclear how metabolic processes, including amino acid metabolism, affect neuronal function and consequently modulate animal behaviors. PRODH, which catalyzes the first step of proline degradation, has been reported as a susceptibility gene for schizophrenia.

Efficacy and Safety of Ferric Citrate on Hyperphosphatemia among Chinese Patients with Chronic Kidney Disease Undergoing Hemodialysis: A Phase III Multicenter Randomized Open-Label Active-Drug-Controlled Study.

Introduction: Hyperphosphatemia in chronic kidney disease (CKD) patients is positively associated with mortality. Ferric citrate is a potent phosphorus binder that lowers serum phosphorus level and improves iron metabolism. We compared its efficacy and safety with active drugs in Chinese CKD patients with hemodialysis.

Autologous Airway Basal Cell Transplantation Alleviates Airway Epithelium Defect in Recurrent Benign Tracheal Stenosis.

Background: Airway epithelium defects are a hallmark of recurrent benign tracheal stenosis (RBTS). Reconstructing an intact airway epithelium is of great importance in airway homeostasis and epithelial wound healing and has great potential for treating tracheal stenosis.

Methods: An experimental study was conducted in canines to explore the therapeutic effect of autologous basal cell transplantation in restoring airway homeostasis.

KCTD4 interacts with CLIC1 to disrupt calcium homeostasis and promote metastasis in esophageal cancer.

Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis.

The progresses of relevant factors on the efficacy of immune checkpoint inhibitors in the non-small cell lung cancer patients.

Lung cancer has the highest mortality rate of all cancers worldwide. Although immune checkpoint inhibitor (ICI)-based therapy can improve the survival of patients with lung cancer, its efficacy is affected by many factors. Therefore, it is necessary to identify factors that affect the efficacy of ICI-based treatment and establish a model for predicting drug response and resistance before and during treatment for individualized and accurate treatment of patients.

Mechanical stretch promotes apoptosis and impedes ciliogenesis of primary human airway basal stem cells.

Background: Airway basal stem cells (ABSCs) have self-renewal and differentiation abilities. Although an abnormal mechanical environment related to chronic airway disease (CAD) can cause ABSC dysfunction, it remains unclear how mechanical stretch regulates the behavior and structure of ABSCs. Here, we explored the effect of mechanical stretch on primary human ABSCs.

Vacuum-Assisted Conventional Minimally Invasive Percutaneous Nephrolithotomy for the Treatment of Two-to-Four-Centimeter Stones: A Multicenter Prospective and Randomized Trial.

Percutaneous nephrolithotomy (PCNL) is the recommended treatment for 2-4-cm renal stones. Minimally invasive PCNL (MPCNL) with ≤22F sheath was frequently used instead of standard PCNL. MPCNL uses pressurized irrigation to flush out stone fragments through a conventional nephrostomy sheath (cNS), which may result in higher intrarenal pressure (IRP) and longer operating time.

BCL11B and the NuRD complex cooperatively guard T-cell fate and inhibit OPA1-mediated mitochondrial fusion in T cells.

The nucleosome remodeling and histone deacetylase (NuRD) complex physically associates with BCL11B to regulate murine T-cell development. However, the function of NuRD complex in mature T cells remains unclear. Here, we characterize the fate and metabolism of human T cells in which key subunits of the NuRD complex or BCL11B are ablated.

An EMT-related genes signature as a prognostic biomarker for patients with endometrial cancer.

Background: The epithelial-mesenchymal transition (EMT) plays an indispensable role in the development and progression of Endometrial cancer (EC). Nevertheless, little evidence is reported to uncover the functionality and application of EMT-related molecules in the prognosis of EC. This study aims to develop novel molecular markers for prognosis prediction in patients with EC.