Impact of Methotrexate and 7-Hydroxymethotrexate Exposure on Renal Toxicity in Pediatric Non-Hodgkin Lymphoma.

Background: 7-Hydroxymethotrexate (7-OHMTX) is the main metabolite in plasma following high-dose MTX (HD-MTX), which may result in activity and toxicity of the MTX. Moreover, 7-OHMTX could produce crystalline-like deposits within the renal tubules under acidic conditions or induce renal inflammation, oxidative stress, and cell apoptosis through various signaling pathways, ultimately leading to kidney damage. The objectives of this study were thus to explore the exposure-safety relationship of two compounds and search the most reliable marker for predicting HDMTX nephrotoxicity.

The efficacy and safety of thymosin α1 for sepsis (TESTS): multicentre, double blinded, randomised, placebo controlled, phase 3 trial.

Objective: To evaluate whether the immunomodulatory drug thymosin α1 reduces mortality in adults with sepsis.

Design: Multicentre, double blinded, placebo controlled phase 3 trial.

Setting: 22 centres in China, September 2016 to December 2020.

Association analysis of genetic polymorphisms of METTL3 with clinical outcomes in a Chinese pediatric population with primary brain tumors.

Background: Methyltransferase-like 3 (METTL3) regulates numerous biological processes and diverse cancers.

Objective: To explore the frequency distribution of METTL3 rs1061026, rs1139130, and rs1263801 polymorphisms, and their potential impacts on clinical outcomes and chemotherapy-induced toxicities in a cohort of Chinese pediatric patients diagnosed with primary brain tumors (PBTs).

Methods: Genotyping for three investigated SNPs was performed in 107 pediatric patients with PBTs using the Sequenom MassARRAY iPLEX platform.

Effects of SCT genetic polymorphisms on methotrexate concentrations and toxicities in Chinese children with acute lymphoblastic leukemia.

Solute carrier (SLC) transporters play a crucial role in facilitating the cellular uptake of various anticancer drugs, such as methotrexate (MTX). This study aimed to analyze the impact of nonsynonymous single nucleotide polymorphisms (SNPs) in , , and on MTX exposure, toxicities, and prognosis in 148 patients with acute lymphoblastic leukemia (ALL). The rs7311358 polymorphism was significantly associated with the median dose-normalized MTX concentrations at 24 h ( < .

Evaluation of Auricular Acupressure on Myopia Prevention among Children Aged 6-12 Years with Pre-Myopia in China: Study Protocol of a Prospective Multi-Center Randomized Controlled Trial.

Background: The increasing prevalence of myopia among Chinese children and adolescents, especially at younger ages, has emerged as a significant concern in recent years. Pre-myopia is a key period for myopia prevention and control in children and adolescents. Previous studies suggested auricular acupressure (AA) therapy might offer a viable approach to prevent and slow down myopia progression.

Single-nucleus transcriptome profiling provides insights into the pathophysiology of adhesive arachnoiditis.

Adhesive arachnoiditis (AA) is a rare form of chronic degenerative pathology associated with persistent inflammation in the arachnoid matter of the spinal cord. Despite the existing knowledge, the detailed pathological mechanisms underlying AA are not fully understood. This study aimed to elucidate through comprehensive single nuclei RNA sequencing (snRNA-seq) to delineate the transcriptomic landscape of AA.

Association of Reduced Folate Carrier G80A Polymorphism With Lung Cancer Susceptibility in a Hypertensive Population: A Nested Case-Control Study.

Background: Polymorphisms of the folate-associated 1-carbon metabolism (OCM) pathway genes may regulate certain susceptibilities to cancer. G80A, a polymorphism in the reduced folate carrier (RFC) gene, may be associated with cancer risk, although the results obtained from previous studies have been inconsistent.

Objectives: This study aimed to evaluate the association of G80A with lung cancer among a Chinese population and to examine the potential effect modifiers.

Building global collaborative research networks in paediatric critical care: a roadmap.

Paediatric critical care units are designed for children at a vulnerable stage of development, yet the evidence base for practice and policy in paediatric critical care remains scarce. In this Health Policy, we present a roadmap providing strategic guidance for international paediatric critical care trials. We convened a multidisciplinary group of 32 paediatric critical care experts from six continents representing paediatric critical care research networks and groups.

Exploring the molecular mechanisms by which secretory phospholipase a2 regulates lymphatic endothelial cell dysfunction by activating macrophages.

This study offers new insights into the dual role of secretory phospholipase A2 (sPLA2) in lymphedema, highlighting its impact on lymphatic endothelial cell (LEC) functionality. Through transcriptomic analyses and co-culture experiments, we observed that sPLA2 has both protective and detrimental effects on human LECs (HLECs), mediated by macrophage activation. Our findings reveal that while low levels of sPLA2 promote LEC health, excessive sPLA2 leads to dysfunction, emphasizing the significance of the sPLA2/PLA2R axis and arachidonic acid metabolism (AA) in lymphedema pathology.

Causal Relationships Between Epilepsy, Anti-Epileptic Drugs, and Serum Vitamin D and Vitamin D Binding Protein: A Bidirectional and Drug Target Mendelian Randomization Study.

Aims: Previous studies suggest potential associations between epilepsy, anti-epileptic drugs (AEDs), and levels of vitamin D and vitamin D-binding protein (VDBP). This study aims to investigate the causal relationships among these variables using Mendelian Randomization (MR) methods.

Methods: Using summary data from genome-wide association studies on serum 25-hydroxyvitamin D [25(OH)D] levels (N = 417,580), VDBP concentrations (N = 65,589), and various types of epilepsy (Ncases = 27,559), MR analyses were conducted to determine bidirectional causal relationships among these variables.

Clinical outcomes and safety of CAR-T cells in treatment of T-Cell acute lymphoblastic leukemia/lymphoma.

Relapsed or refractory T-cell acute lymphoblastic leukemia/lymphoma (r/r T-ALL/LBL) are frequently aggressive and associated with unfavorable prognoses. Pan-targeted Chimeric Antigen Receptor (CAR) T-cell therapy have shown promising results in clinical trials. In recent years, CD7 CAR T-cell and CD5 CAR T-cell demonstrate effectiveness in treating r/r T-ALL/LBL patients with bone marrow infiltration.

Quantitative proteomic landscape of the pathophysiology of adhesive arachnoiditis and its clinical significance: Structure and mechanism of TNC and RANBP1 proteins.

The pathophysiological mechanism of adhesive arachnoiditis (AA) is complex, involving the interaction of multiple proteins. In recent years, the development of quantitative proteomics technology has provided a new perspective to reveal its pathological mechanism. The main objective of this study was to reveal the changes of protein expression profiles in arachnoid tissue of patients with AA.

Evaluation of Olaparib Tablet Safety and Pharmacokinetics in Healthy Chinese Male Subjects.

Purpose: To evaluate the safety and pharmacokinetics of olaparib tablet test formulation (T) and reference formulation (R) in healthy Chinese male subjects.

Subjects And Methods: This was a single-dose, randomized-sequence, two-way crossover study including three parts: part A: a safety exploration design in lower dose (n = 14, 100 mg), part B: a pivotal comparative pharmacokinetic (PK) trial under fast condition (n = 44, 150 mg) and part C: a pivotal comparative PK trial under food condition (n = 44, 150 mg). Blood samples were collected for 72 hours and the PK parameters of C, AUC and AUC were used to evaluate PK differences.

Prognostic value of β1 adrenergic receptor autoantibodies for microvascular obstruction in patients with STEMI with Post-PCI: A prospective cohort study.

Backgrounds: Coronary microvascular obstruction (MVO) frequently occurs in patients with ST-segment elevation myocardial infarction (STEMI) following percutaneous coronary intervention (PCI), leading to poor prognosis. β adrenergic receptor autoantibodies (β-AA) are present in various cardiovascular diseases and correlate with cardiac damage and dysfunction. However, whether β-AA is associated with the occurrence of MVO in patients with STEMI after PCI remains unclear.

HIV-1 viral decay in blood and semen in antiretroviral-naïve adults initiating dolutegravir/lamivudine vs. bictegravir/emtricitabine/tenofovir alafenamide.

Background: Co-formulated dolutegravir and lamivudine (DTG/3TC) is recommended as the first-line antiretroviral therapy (ART); however, the data on the viral decay in seminal plasma (SP) and blood plasma (BP), as well as changes in inflammatory biomarkers in BP, remain limited among antiretroviral-naïve people with HIV (PWH) receiving DTG/3TC. A prospective observational cohort study was conducted to compare the impact of DTG/3TC vs. bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) on viral decay kinetics and changes in inflammatory biomarkers in antiretroviral-naïve PWH.

The Safety, Tolerability, and Pharmacokinetics of Active Ingredients From Hydroxysafflor Yellow A in Healthy Chinese Volunteers.

Hydroxysafflor yellow A (HSYA), an active ingredient extracted from Carthami flos, shows potential for treating ischemic stroke. This phase 1 study assessed the safety, tolerability, and pharmacokinetic (PK) properties of HSYA in healthy Chinese volunteers who received intravenous infusions of pure HSYA powder. The study comprised 2 parts.

Analysis of clinical characteristics and risk factors on serrated polyps with synchronous advanced adenoma in elderly and non-elderly people: a retrospective cohort study.

Objectives: Serrated polyps (SPs) with synchronous advanced adenoma (AA) may increase the incidence of colorectal cancer. However, current studies do not address this combination of SPs and AAs in detail with regard to their clinical characteristics in different age groups. The aim was to assess clinical characteristics and risk factors for SPs with synchronous AA in different age groups.

The role of mA modification in cardiovascular disease: A systematic review and integrative analysis.

Background And Aims: This study focused on the recent advancements in understanding the association between N6-methyladenosine (mA) modification and cardiovascular disease (CVD).

Methods: The potential mechanisms of mA related to CVD were summarized by literature review. Associations between mA levels and CVD were explored across 8 electronic databases: PubMed, Embase, Web of Science, Cochrane Library, Sinomed, Wan Fang, CNKI, and Vip.

ANK Deficiency-Mediated Cytosolic Citrate Accumulation Promotes Aortic Aneurysm.

Background: Disturbed metabolism and transport of citrate play significant roles in various pathologies. However, vascular citrate regulation and its potential role in aortic aneurysm (AA) development remain poorly understood.

Methods: Untargeted metabolomics by mass spectrometry was applied to identify upregulated metabolites of the tricarboxylic acid cycle in AA tissues of mice.

m6A-methylase METTL3 promotes retinal angiogenesis through modulation of metabolic reprogramming in RPE cells.

Retinal neovascularization (RNV) disease is one of the leading causes of blindness, yet the molecular underpinnings of this condition are not well understood. To delve into the critical aspects of cell-mediated angiogenesis, we analyzed our previously published single-cell data. Our analysis revealed that retinal pigment epithelium (RPE) cells serve a crucial promotional function in angiogenesis.

An integrative lipidomics and transcriptomics study revealing Bavachin and Icariin synergistically induce idiosyncratic liver injury.

Reports of traditional Chinese medicine (TCM)-related liver injury have increased over recent years; however, identifying susceptibility-related components and biomarkers remains challenging due to the heterogeneous nature of TCM and idiosyncratic drug-induced liver injury (IDILI). (PF) and (EF), commonly found in TCM prescriptions, have been implicated in IDILI, but their constituents and underlying mechanisms are poorly understood. In this study, we identified bavachin (Bav) and icariin (Ica) as susceptibility components for IDILI in PF and EF using a TNF-α-mediated mouse model.

A Core-Brush Nanoplatform with Enhanced Lubrication and Anti-Inflammatory Properties for Osteoarthritis Treatment.

Osteoarthritis (OA) is recognized as a highly friction-related joint disease primarily associated with increased joint friction and inflammation due to pro-inflammatory M1-type macrophage infiltration in the articular cavity. Therefore, strategies to simultaneously increase lubrication and relieve inflammation to remodel the damaged articular microenvironment are of great significance for enhancing its treatment. Herein, a multifunctional core-brush nanoplatform composed of a ROS-scavenging polydopamine-coated SiO core and lubrication-enhancing zwitterionic poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) brush and loaded with the anti-inflammatory drug curcumin by a reactive oxygen species (ROS)-liable conjugation (named as SiO@PP-Cur) is rationally designed.

The NAD precursor nicotinamide riboside protects against postovulatory aging in vitro.

Purpose: Postovulatory aging (POA) of oocytes is clinically significant as it mirrors the degeneration observed in maternally aged oocytes, leading to substantial impairments in oocyte quality and the success rates of artificial reproductive technology (ART). The molecular alterations associated with POA, such as the degeneration of the first polar body, an increase in perivitelline space, reactive oxygen species (ROS) accumulation, energy depletion, and chromosomal and DNA damage, underscore the urgency of finding interventions to mitigate these effects. This study aims to identify whether nicotinamide riboside (NR) can prevent POA during the process of in vitro culture and raise the success rates of ART.