Association of genetically proxied cancer-targeted drugs with cardiovascular diseases through Mendelian randomization analysis.

Background: Cancer-targeted therapies are progressively pivotal in oncological care. Observational studies underscore the emergence of cancer therapy-related cardiovascular toxicity (CTR-CVT), impacting patient outcomes. We aimed to investigate the causal relationship between different types of cancer-targeted therapies and cardiovascular disease (CVD) outcomes through a two-sample Mendelian randomization (MR) study.

Targeting mA demethylase FTO to heal diabetic wounds with ROS-scavenging nanocolloidal hydrogels.

Chronic diabetic wounds are a prevalent and severe complication of diabetes, contributing to higher rates of limb amputations and mortality. N6-methyladenosine (mA) is a common RNA modification that has been shown to regulate tissue repair and regeneration. However, whether targeting mA could effectively improve chronic diabetic wound healing remains largely unknown.

Efficacy and Safety of SHR8554 on Postoperative Pain in Subjects with Moderate to Severe Acute Pain Following Orthopedic Surgery: A Multicenter, Randomized, Double-blind, Dose-explored, Active-controlled, Phase II/III Clinical Trial.

Biased µ-opioid receptor (MOR) agonists enhance pain relief by selectively activating G protein-coupled receptor signaling and minimizing β-arrestin-2 activation, resulting in fewer side effects. This multicenter Phase II/III trial evaluated the optimal dosage, efficacy, and safety of SHR8554, a biased MOR agonist, for postoperative pain management following orthopedic surgery. In Phase II, 121 patients were divided into four groups to receive varying patient-controlled analgesia (PCA) doses of SHR8554 or morphine.

Lipidomic analysis of plant-derived extracellular vesicles for guidance of potential anti-cancer therapy.

Plant-derived extracellular vesicles (PEVs) have been regarded as a superior source for nanomedicine and drug delivery systems. Nevertheless, their clinical translation is hindered by the lack of clarity and even contradiction in their biomedical applications. Herein, we conducted a comprehensive compositional analysis of four commonly used PEVs to fully understand their functional lipid contents and assess their potential therapeutic applications.

Risk classification for non-cancer death in middle-aged cancer patients.

Introduction: Non-cancer events are important causes of competing mortality among cancer patients. However, the risk of non-cancer death and risk classification in middle-aged cancer patients is not clear. To comprehensively analyze the risk of non-cancer deaths in 24 different cancers among middle-aged patients.

PEARL: A Multicenter Phase 2 Study of Lorlatinib in Patients with ALK-Rearranged NSCLC and Central Nervous System Disease.

Background: Patients with ALK-rearranged non-small cell lung cancer (ALK+ NSCLC) with symptomatic brain (BM) and leptomeningeal (LM) metastases are underrepresented in clinical trials due to poor performance status. Additionally, the need for improved and validated assessment criteria for evaluating central nervous system (CNS) response remains critical. Lorlatinib has demonstrated systemic activity in patients with ALK+ NSCLC.

Tumor-Targeted Magnetic Micelles for Magnetic Resonance Imaging, Drug Delivery, and Overcoming Multidrug Resistance.

Nasopharyngeal carcinoma (NPC) is prevalent in Southern China. Unfortunately, current treatments encounter multidrug resistance (MDR). Overexpression of P-glycoprotein (P-gp), resulting in the efflux of chemotherapy drugs, is one of the significant mechanisms causing MDR.

Overexpression of Growth Differentiation Factor 15 Reduces Neuronal Cell Damage Induced by Oxygen-Glucose Deprivation/Reoxygenation via Inhibiting Endoplasmic Reticulum Stress-Mediated Ferroptosis.

Growth differentiation factor 15 (GDF15) can be induced under various stress conditions. This study aimed to explore the role of GDF15 in oxygen-glucose deprivation/reoxygenation (OGD/R)-induced HT22 cells. OGD/R was employed to induce the HT22 cell model, and GDF15 expression was upregulated via transfection.

Oral probiotic extracellular vesicle therapy mitigates Influenza A Virus infection via blunting IL-17 signaling.

The influenza A virus (IAV) damages intestinal mucosal tissues beyond the respiratory tract. Probiotics play a crucial role in maintaining the balance and stability of the intestinal microecosystem. Extracellular vesicles (EVs) derived from probiotics have emerged as potential mediators of host immune response and anti-inflammatory effect.

GG-NER's role in androgen receptor signaling inhibitor response for advanced prostate cancer.

Background: Advanced prostate cancer (PCa) often initially responds to androgen receptor signaling inhibitors (ARSI) but frequently develops resistance, driven by tumor heterogeneity and therapeutic pressure. Addressing the clinical challenge of identifying non-responsive patients and discovering new therapeutic targets is urgently needed.

Methods: We utilized single-sample gene set enrichment analysis (ssGSEA) to elucidate the influence of the GG-NER pathway on ARSI response in PCa.

Linking Gut Microbiota, Oral Microbiota, and Serum Metabolites in Insomnia Disorder: A Preliminary Study.

Purpose: Despite recent findings suggesting an altered gut microbiota in those suffering from insomnia disorder (ID), research into the gut microbiota, oral microbiota, serum metabolites, and their interactions in patients with ID is sparse.

Patients And Methods: We collected a total of 114 fecal samples, 133 oral cavity samples and 20 serum samples to characterize the gut microbiota, oral microbiota and serum metabolites in a cohort of 76 ID patients (IDs) and 59 well-matched healthy controls (HCs). We assessed the microbiota as potentially biomarkers for ID for ID by 16S rDNA sequencing and elucidated the interactions involving gut microbiota, oral microbiota and serum metabolites in ID in conjunction with untargeted metabolomics.

Late-Stage Rapid [F]Trifluoromethyl Radiolabeling of Terminal Alkenes at Room Temperature.

We report an efficient, metal-free method for late-stage rapid [F]trifluoromethyl radiolabeling of terminal alkenes at room temperature. Utilizing 3,3-difluoroallyl sulfonium salts as precursors, the process achieves high radiochemical yields (up to 94 ± 2%) in just 30 s, with excellent functional group tolerance. This method offers a simplified and efficient pathway to produce [F]trifluoromethylated terminal alkene compounds, enabling their application in PET imaging and expanding the chemical space for drug discovery.

Integrated analyses of multi-omic data derived from paired primary lung cancer and brain metastasis reveal the metabolic vulnerability as a novel therapeutic target.

Background: Lung cancer brain metastases (LC-BrMs) are frequently associated with dismal mortality rates in patients with lung cancer; however, standard of care therapies for LC-BrMs are still limited in their efficacy. A deep understanding of molecular mechanisms and tumor microenvironment of LC-BrMs will provide us with new insights into developing novel therapeutics for treating patients with LC-BrMs.

Methods: Here, we performed integrated analyses of genomic, transcriptomic, proteomic, metabolomic, and single-cell RNA sequencing data which were derived from a total number of 154 patients with paired and unpaired primary lung cancer and LC-BrM, spanning four published and two newly generated patient cohorts on both bulk and single cell levels.

S1PR1 suppresses lung adenocarcinoma progression through p-STAT1/miR-30c-5 p/FOXA1 pathway.

Background: Sphingosine-1-phosphate receptor 1 (S1PR1) is considered to be closely related to a variety of malignant tumors, but the role and mechanism of S1PR1 in lung adenocarcinoma are not fully understood. In this study, we aim to explore the role and downstream signaling pathways of S1PR1 in the malignant biological functions of lung adenocarcinoma (LUAD).

Methods: Bioinformatics analysis, RT-qPCR, western blot and immunohistochemistry (IHC) were was used to investigate the expression of S1PR1 in LUAD.

The global status of bioequivalence trials: a comprehensive clinical trial landscape analysis based on the Trialtrove database.

This study presents a comprehensive analysis of the global bioequivalence (BE) trial landscape over the past 21 years, utilizing data from the Trialtrove database. We analyzed 12,450 BE trials conducted from 2003 to 2023, revealing a significant upward trend in trial numbers. Among the analysis, the primary therapeutic areas identified were cardiovascular diseases (23.

Biologically logic-gated Trojan-horse strategy for personalized triple-negative breast cancer precise therapy by selective ferroptosis and STING pathway provoking.

Amidst the therapeutic quandaries associated with triple-negative breast cancer (TNBC), an aggressive malignancy distinguished by its immune resistance and limited treatment avenues, the urgent need for innovative solutions is underscored. To conquer the dilemma, we present a groundbreaking approach that ingeniously employs DNA-fragments-containing exosomes (DNA-Exo) and the concept of "biological logic-gates" to achieve precise homing and controlled selective activation of ferroptosis and stimulator interferon genes (STING) pathways. Leveraging insights from our previous research, a nano-Trojan-horse, Fe@HMON@DNA-Exo, is engineered via in situ Fe synthesis within the glutathione (GSH)-responsiveness degradable hollow mesoporous organosilica nanoparticles (HMON) and subsequently enveloped in DNA-Exo derived from 7-ethyl-10-hydroxycamptothecin (SN38)-treated 4T1 cells.

A multicenter bladder cancer MRI dataset and baseline evaluation of federated learning in clinical application.

Bladder cancer (BCa), as the most common malignant tumor of the urinary system, has received significant attention in research on the clinical application of artificial intelligence algorithms. Nevertheless, it has been observed that certain investigations use data from various medical facilities to train models for BCa, which may pose a privacy risk. Given this concern, protecting patient privacy during machine learning algorithm training is a crucial aspect that requires substantial attention.

Intense simplified strategy for newly diagnosed type 2 diabetes in patients with severe hyperglycaemia: multicentre, open label, randomised trial.

Objective: To evaluate whether the intense simplified strategy, which comprises short term intensive insulin therapy (SIIT) followed by subsequent oral antihyperglycaemic regimens, could improve long term glycaemic outcomes in patients with newly diagnosed type 2 diabetes mellitus and severe hyperglycaemia.

Design: Multicentre, open label, randomised trial.

Setting: 15 hospitals in China between December 2017 and December 2020.

NLRP3 inhibitor combined with Yimusake improves erectile dysfunction in rats with diabetes mellitus through the attenuation of pyroptosis.

Erectile dysfunction (ED) is a prevalent complication associated with diabetes mellitus (DM), yet pharmacological treatments for diabetes-related erectile dysfunction (DMED) continue to be inadequate in clinical settings. Our previous studies have indicated that there is a close correlation between ED and pyroptosis, but the specific mechanism remains unclear. In this study, we sought to explore the therapeutic effects of DMED through the modulation of NLRP3, aiming to elucidate its potential molecular mechanisms.