Liquid chromatography-tandem mass spectrometry for the quantification of ripretinib and its metabolites DP-5439 in human plasma.

Background: Ripretinib, a broad-spectrum tyrosine kinase inhibitor, has been approved for the treatment of advanced gastrointestinal stromal tumors in adult patients. Clinical studies have shown that higher exposure of ripretinib correlates with improved efficacy, highlighting the potential clinical significance of therapeutic drug monitoring. In this study, a simple and stable liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was attempted to be established and validated for pharmacokinetic studies of ripretinib and its metabolite DP-5439 and therapeutic drug monitoring in human plasma.

Dysfunction in mitochondrial electron transport chain drives the pathogenesis of pulmonary arterial hypertension: insights from a multi-omics investigation.

Background: Pulmonary arterial hypertension (PAH) is a progressive disorder that can lead to right ventricular failure and severe consequences. Despite extensive efforts, limited progress has been made in preventing the progression of PAH. Mitochondrial dysfunction is implicated in the development of PAH, but the key mitochondrial functional alterations in the pathogenesis have yet to be elucidated.

Risk factors for mediastinal lymph node metastases in early-stage non-small-cell lung cancer and prediction model establishment.

This study aimed to explore the risk factors for mediastinal lymph node metastases (MLNM) in patients with early-stage non-small-cell lung cancer (NSCLC) and to establish a predictive model. A retrospective analysis was conducted on the clinical data from NSCLC patients treated at the Second Affiliated Hospital of Guangzhou Medical University and the First Affiliated Dongguan Hospital of Guangdong Medical University between March 2021 and March 2023. Baseline clinical data, laboratory parameters, and pathological features were collected and analyzed.

Glecirasib in KRAS-mutated nonsmall-cell lung cancer: a phase 2b trial.

Glecirasib (JAB-21822) is a new covalent oral KRAS-G12C inhibitor. This multicenter, single-arm phase 2b study assessed the efficacy and safety of glecirasib administered orally at 800 mg daily in patients with locally advanced or metastatic KRAS-mutated nonsmall-cell lung cancer. The primary endpoint was the objective response rate (ORR) assessed by an independent review committee (IRC).

Diagnosis value of targeted and metagenomic sequencing in respiratory tract infection.

Background: Targeted next-generation sequencing (tNGS) has become a trending tool in the field of infection diagnosis, but concerns are also raising about its performance compared with metagenomic next-generation sequencing (mNGS). This study aims to explore the clinical feasibility of a tNGS panel for respiratory tract infection diagnosis and compare it with mNGS in the same cohort of inpatients.

Methods: 180 bronchoalveolar lavage fluid samples were collected and sent to two centers for mNGS and tNGS blinded tests, respectively.

Loop33 × 123 CAR-T targeting CD33 and CD123 against immune escape in acute myeloid leukemia.

Background: Immunotherapy, such as chimeric antigen receptor T (CAR-T) cells targeting CD33 or CD123, has been well developed over the past decade for the treatment of acute myeloid leukemia (AML). However, the inability to sustain tumor-free survival and the possibility of relapse due to antigen loss have raised concerns. A dual targeting of CD33 and CD123 is needed for better outcomes.

Construction of a lung cancer 3D culture model based on alginate/gelatin micro-beads for drug evaluation.

Background: Lung cancer is one of the most common malignant tumors worldwide. Despite advances in lung cancer treatment, patients still face challenges related to drug resistance and recurrence. Current methods for evaluating anti-cancer drug activity are insufficient, as they rely on two-dimensional (2D) cell culture and animal models.

Targeting Fatty Acid Metabolism Abrogates the Differentiation Blockade in Preleukemic Cells.

Metabolism plays a key role in the maintenance of normal hematopoietic stem cells (HSC) and in the development of leukemia. A better understanding of the metabolic characteristics and dependencies of preleukemic cells could help identify potential therapeutic targets to prevent leukemic transformation. As AML1-ETO, one of the most frequent fusion proteins in acute myeloid leukemia that is encoded by a RUNX1::RUNX1T1 fusion gene, is capable of generating preleukemic clones, in this study, we used a conditional Runx1::Runx1t1 knockin mouse model to evaluate preleukemic cell metabolism.

Identifying ADGRG1 as a specific marker for tumor-reactive T cells in acute myeloid leukemia.

Besides chemotherapy and hematopoietic stem cell transplantation (HSCT), autologous T cells can also serve as a new treatment approach for AML patients. However, the features of tumor-reactive T cells and their distinctive markers still lack full description. To evaluate the characteristics of tumor-reactive T cells, we collected bone marrow (BM) T cells from newly diagnosed AML patients with RUNX1::RUNX1T1 as examples for paired single-cell RNA sequencing and single-cell V(D)J sequencing.

Incidence, clinical classification and risk factors of cyclosporin A-induced liver injury in allogeneic haematopoietic stem cell transplant recipients.

Aims: There is limited real-world data on cyclosporin A (CsA)-induced liver injury (CILI). This study aims to investigate the incidence, clinical classification and risk factors of CILI, thereby providing evidence to inform the treatment of CILI.

Methods: Inpatients receiving haematopoietic stem cell transplantation (HSCT) and treated with CsA were included.

H3K27ac acts as a molecular switch for doxorubicin-induced activation of cardiotoxic genes.

Background: Doxorubicin (Dox) is an effective chemotherapeutic drug for various cancers, but its clinical application is limited by severe cardiotoxicity. Dox treatment can transcriptionally activate multiple cardiotoxicity-associated genes in cardiomyocytes, the mechanisms underlying this global gene activation remain poorly understood.

Methods And Results: Herein, we integrated data from animal models, CUT&Tag and RNA-seq after Dox treatment, and discovered that the level of H3K27ac (a histone modification associated with gene activation) significantly increased in cardiomyocytes following Dox treatment.

A dual-targeting approach with anti-IL10R CAR-T cells engineered to release anti-CD33 bispecific antibody in enhancing killing effect on acute myeloid leukemia cells.

Background: Immunotherapies, including chimeric antigen receptor (CAR) T cells and bispecific antibodies (BsAbs), encounter several challenges in the management of acute myeloid leukemia (AML), including limited persistence of these treatments, antigen loss and resistance of leukemia stem cells (LSCs) to therapy.

Methods: Here, we proposed a novel dual-targeting approach utilizing engineered anti-IL10R CAR-T cells to secrete bispecific antibodies targeting CD33. This innovative strategy, rooted in our previous research which established a connection between IL-10 and the stemness of AML cells, designed to improve targeting efficiency and eradicate both LSCs and AML blasts.

Circulating tumor cells with increasing aneuploidy predict inferior prognosis and therapeutic resistance in small cell lung cancer.

Aims: Treatment resistance commonly emerges in small cell lung cancer (SCLC), necessitating the development of novel and effective biomarkers to dynamically assess therapeutic efficacy. This study aims to evaluate the clinical utility of aneuploid circulating tumor cells (CTCs) for risk stratification and treatment response monitoring.

Methods: A total of 126 SCLC patients (two cohorts) from two independent cancer centers were recruited as the study subjects.

Exploring susceptibility factors to medication dispensing errors through a retrospective study of patient-reported dispensing errors over 11 years: are dispensing errors indeed due to personal reasons for pharmacists?

Background: Medication dispensing errors cause wastage of medicines and increase healthcare costs, with serious consequences for patients. However, few studies have systematically and completely reviewed dispensing errors, with inadequate attention to the objective regularity and risk factors for dispensing errors.

Objectives: To explore the potential causes and risk factors influencing the prevalence of medication dispensing errors.

Optimal exposure of mycophenolic acid for induction therapy of childhood lupus nephritis patients: an observational cohort study.

Objectives: Mycophenolic acid (MPA) is recommended for lupus nephritis (LN) treatment, but with large inter-individual variability in pharmacokinetics (PK). The aim of this study is to reveal the relationship between MPA exposure and disease response and adverse drug reactions in pediatric LN patients.

Method: This was a population-based observational cohort study.

Activating innate immune responses repolarizes hPSC-derived CAR macrophages to improve anti-tumor activity.

Generation of chimeric antigen receptor macrophages (CAR-Ms) from human pluripotent stem cells (hPSCs) offers new prospects for cancer immunotherapy but is currently challenged by low differentiation efficiency and limited function. Here, we develop a highly efficient monolayer-based system that can produce around 6,000 macrophages from a single hPSC within 3 weeks. Based on CAR structure screening, we generate hPSC-CAR-Ms with stable CAR expression and potent tumoricidal activity in vitro.

Pharmacokinetics of nirmatrelvir/ritonavir and the drug-drug interaction with calcineurin inhibitor in renal transplant recipients.

Objectives: To describe the pharmacokinetic (PK) characteristics of nirmatrelvir/ritonavir in renal transplant recipients and explore the potential factors that related to the PK variance of nirmatrelvir/ritonavir and its interaction with calcineurin inhibitor (CNI).

Methods: Renal transplant recipients treated with CNI and nirmatrelvir/ritonavir were prospectively enrolled. Steady-state plasma concentrations of nirmatrelvir/ritonavir were determined by high-performance liquid chromatography-tandem mass spectrometry, and the PK parameters were calculated using non-compartmental analysis.

The impact of EGFR T790M mutation status following the development of Osimertinib resistance on the efficacy of Osimertinib in non-small cell lung cancer: A meta-analysis.

Background: Previous studies have suggested that loss of the EGFR T790M gene mutation may contribute to the development of resistance to Osimertinib in non-small cell lung cancer (NSCLC).

Aims: This study aims to assess the relationship between the clinical effectiveness of Osimertinib in NSCLC patients and the T790M mutation status following resistance to Osimertinib and examine differences between plasma and tissue tests and between Asian and non-Asian groups.

Methods: The PubMed, Web of Science, Cochrane, and EMBASE databases were comprehensively searched for studies on the association between T790M mutation status and the efficacy of Osimertinib between January 2014 and November 2023.

Identification of a DNA-methylome-based signature for prognosis prediction in driver gene-negative lung adenocarcinoma.

"Driver gene-negative" lung adenocarcinoma (LUAD) was of rare treatment options and a poor prognosis. Presently, for them, few biomarkers are available for stratification analysis to make appropriate treatment strategy. This study aimed to develop a DNA-methylome-based signature to realize the precise risk-stratifying.

Comparison of osimertinib plus bevacizumab against osimertinib alone in NSCLC harboring EGFR mutations: a systematic review and meta-analysis.

Background: Frequent failures observed in some trials comparing the efficacy and safety of osimertinib plus bevacizumab to osimertinib monotherapy in advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) alterations have brought questions.

Objectives: To evaluate the efficacy and safety of these two treatment regimens in advanced NSCLC patients harboring EGFR mutations.

Design: This study is a systematic review and meta-analysis.