Enhanced fibrotic potential of COL1A1NR4A1 fibroblasts in ischemic heart revealed by transcriptional dynamics heterogeneity analysis at both bulk and single-cell levels.

Background: Fibroblasts in the fibrotic heart exhibit a heterogeneous biological behavior. The specific subsets of fibroblasts that contribute to progressive cardiac fibrosis remain unrevealed. Our aim is to identify the heart fibroblast (FB) subsets that most significantly promote fibrosis and the related critical genes as biomarkers for ischemic heart disease.

Efficacy and safety of KN026 and docetaxel for HER2-positive breast cancer: a phase II clinical trial.

Background: The standard first-line treatment for human epidermal growth factor receptor 2 (HER2)-positive recurrent/metastatic breast cancer currently includes pertuzumab plus trastuzumab and docetaxel. This study aimed to evaluate the effectiveness of KN026, an anti-HER2 bispecific antibody, plus docetaxel in first-line treatment of HER2-positive recurrent/metastatic breast cancer.

Methods: This open-label, single-arm, phase II study enrolled patients with HER2-positive recurrent/metastatic breast cancer in 19 centers across China from December 30, 2019 to May 27, 2021.

KNG1 mutations (c.618 T > G and c.1165C > T) cause disruption of the Cys206-Cys218 disulfide bond and truncation of the D5 domain leading to hereditary high molecular weight kininogen deficiency.

Background: High molecular weight kininogen (HMWK), encoded by the kininogen-1 (KNG1) gene, is a multifunctional glycoprotein closely associated with the initiation of blood coagulation, tumor growth, and other pathological processes.

Objective: We conducted a study on the clinical phenotype, genetic mutations, and molecular pathogenesis of a female patient with uterine leiomyosarcoma, who presented with HMWK deficiency and an isolated prolonged activated partial thromboplastin time (APTT).

Methods: Clinical phenotyping was conducted through APTT mixing studies, quantitative assessments of intrinsic coagulation factor activities, antigen levels of HMWK, and thromboelastography.

Novel compound heterozygous mutations in the LARS2 gene in a Chinese family with hearing loss.

Background: Mutations in the LARS2 gene are correlated with Perrault syndrome, a rare autosomal recessive genetic disorder, that is typically characterized by sensorineural hearing loss and ovarian insufficiency.

Methods: Whole-exome sequencing and mutational analysis were employed to identify hearing loss-causing genes in a Chinese family from the Guangxi Zhuang Autonomous Region. Clinical phenotypes, audiological data, and color Doppler ultrasound of the family were collected, and a series of computer software were used to analyze the impact of genetic variations on protein structure and function.

Assessment of MGMT and TERT Subtypes and Prognosis of Glioblastoma by Whole Tumor Apparent Diffusion Coefficient Histogram Analysis.

Background: Adult glioblastomas (GBMs) are associated with high recurrence and mortality. Personalized treatment based on molecular markers may help improve the prognosis. We aimed to evaluate whether apparent diffusion coefficient (ADC) histogram analysis can better predict MGMT and TERT molecular characteristics and to determine the prognostic relevance of genetic profile in patients with GBM.

Haplotype-Resolved Genotyping and Association Analysis of 1,020 β-Thalassemia Patients by Targeted Long-Read Sequencing.

Despite the well-documented mutation spectra of β-thalassemia, the genetic variants and haplotypes of globin gene clusters modulating its clinical heterogeneity remain incompletely illustrated. Here, a targeted long-read sequencing (T-LRS) is demonstrated to capture 20 genes/loci in 1,020 β-thalassemia patients. This panel permits not only identification of thalassemia mutations at 100% of sensitivity and specificity, but also detection of rare structural variants (SVs) and single nucleotide variants (SNVs) in modifier genes/loci.

Pinocembrin activation of DPP9 inhibits NLRP1 inflammasome activation to alleviate cerebral ischemia/reperfusion-induced lung and intestinal injury.

After stroke, there is a high incidence of acute lung injury and impairment of intestinal barrier function. In this research, the effects of pinocembrin on organ injuries induced by cerebral ischemia-reperfusion were investigated in mice with middle cerebral artery occlusion/reperfusion (MCAO/R) and further explored the possible mechanism. The potential targets of pinocembrin against MCAO/R were obtained by online tools.

Serum metabolome associated with novel and legacy per- and polyfluoroalkyl substances exposure and thyroid cancer risk: A multi-module integrated analysis based on machine learning.

Background: Exposure to per- and polyfluoroalkyl substances (PFAS) may linked to thyroid cancer (TC) risk, but inconsistent findings and a lack of studies on mixed exposures exist, especially regarding novel PFAS compounds. Additionally, little is known about the potential mechanisms underlying the association.

Objectives: Explore the effects of PFAS exposure on the serum metabolome and its correlation with TC.

Impact of Forms of Visual Attenuation on Short-Term Eye Changes Under Controlled Reading Visibility.

Purpose: Animal studies have suggested that visual degradation impacts eye growth due to the attenuation of high spatial frequencies. However, the influence of perceptual visibility remains unclear in humans. The aim of this study was to investigate the impact of visibility on visual attenuation-related eye changes during reading.

Machine Learning and Experimental Validation Identified Ferroptosis Signature and Innovative Biomarkers (ESR1 and GSTZ1) in Liver Fibrosis.

Background: Targeting ferroptosis is an effective approach to mitigate hepatic fibrosis, yet no reports exist on the ferroptosis signature in liver fibrosis. This study aimed to explore ferroptosis characteristics in this disease.

Methods: RNAseq data from GSE6764, GSE188604 and Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) were downloaded.

Role of Endoplasmic Reticulum Stress in Melatonin-induced Apoptosis and Inhibition of Invasion and Migration in Adrenocortical Carcinoma Cells.

Background: Melatonin, a hormone synthesized by the pineal gland and released into the blood, seems to have anti-tumor properties. However, the mechanisms of the anti-cancer effect of melatonin are largely unknown. This study investigated the anti-tumor activity of melatonin in adrenocortical carcinoma (ACC) and analyzed its molecular mechanisms.

A U-shaped relationship between the atherogenic index of plasma and repeated target vessel revascularization in patients undergoing percutaneous coronary intervention: a retrospective study.

Background: Atherogenic index of plasma (AIP) has been recognized as a novel and practical marker for the assessment of cardiometabolic risk, but the relevance of AIP as a prognostic biomarker in coronary artery disease (CAD) remains debated. This study investigated the association between AIP and major adverse cardiac and cerebrovascular events (MACCEs) in CAD patients receiving percutaneous coronary intervention (PCI) with drug-eluting stents (DES).

Methods: A total of 2,250 patients undergoing PCI with DES were included in this retrospective cohort study.

Efficacy and safety of YOXINTINE for depression: A double-blinded, randomized, placebo-controlled, phase 2 clinical trial.

Background: YOXINTINE contains >98 % of 20(S)-protopanaxadial (PPD), a metabolic product of ginsenosides with pre-clinical neuroprotective activity. Animal experiments and previous studies have shown that PPD has good antidepressant effect and safety.

Purpose: To evaluate YOXINTINE in treating depression compared with a placebo in Chinese patients.

The synergistic effect of miR-203 and cytarabine on the inhibition of cell proliferation and induction of apoptosis in chronic myelogenous leukemia cells.

Cytarabine (Ara-C) is a commonly used chemotherapeutic drug for the treatment of leukemia, known for its significant tolerability. The down regulation of miR-203 in leukemia cells suggests its potential involvement in the pathogenesis of leukemia. In this study, we investigated the effects and possible mechanisms of miR-203 and Ara-C on proliferation and apoptosis of human leukemia K562 cells which were cultured with Ara-C and/or with transfection of miR-203 expression vectors.

Irisin suppresses PDGF-BB-induced proliferation of vascular smooth muscle cells by activating AMPK/mTOR-mediated autophagy.

Restenosis is a pivotal factor that restricts the efficacy of coronary artery bypass grafting. Inhibition of vascular smooth muscle cells (VSMCs) proliferation can improve intimal hyperplasia and lumen stenosis. Irisin, a polypeptide secreted by muscle cells, has been demonstrated to have a protective role in various cardiovascular diseases.

Low false-positive lymph nodes for 18 F-fibroblast activation protein inhibitors PET/computed tomography in preoperative staging of patients with nonsmall cell lung cancer.

Objective: This study aimed to evaluate the diagnostic accuracy of 18 F-fibroblast activation protein inhibitor (FAPI) PET/computed tomography (CT) in identifying primary tumors and mediastinal lymph node metastases in nonsmall cell lung cancer (NSCLC), with histopathological findings serving as the reference standard.

Methods: Nineteen patients underwent preoperative 18 F-FAPI PET/CT and subsequent surgery; of these, 13 also underwent 18 F-fluorodeoxyglucose (FDG) PET/CT within 1 week. The diagnostic accuracy of primary tumors and lymph node metastases was evaluated for both modalities.

Hyperuricemia Facilitates Uric Acid-Mediated Vascular Endothelial Cell Damage by Inhibiting Mitophagy.

Hyperuricemia remains an elusive factor in the pathogenesis of vascular endothelial injury. This study elucidates the role of hydroxychloroquine (HCQ) in the context of uric acid (UA)-induced vascular endothelial cell damage. Human umbilical vein endothelial cells (HUVECs) were exposed to varying UA concentrations (6 mg/dL to 50 mg/dL) for 48 h, or to 50 mg/dL UA for different time points (6 to 72 h).