The de novo synthesis of GABA and its gene regulatory function control hepatocellular carcinoma metastasis.

The neurotransmitter gamma-aminobutyric acid (GABA) has been thought to be involved in the development of some types of cancer. Yet, the de novo synthesis of GABA and how it functions in hepatocellular carcinoma (HCC) remain unclear. Here, we report that SLC6A12 acts as a transporter of GABA, and that aldehyde dehydrogenase 9 family member A1 (ALDH9A1), not glutamate decarboxylase 1 (GAD1), generates GABA in human HCC.

ATM/ATR-Mediated DNA Damage Response Facilitates SARS-CoV-2 Spike Protein-Induced Syncytium Formation.

Multinucleated cells are present in lung tissues of patients infected by SARS-CoV-2. Although the spike protein can cause the fusion of infected cells and ACE2-expressing cells to form syncytia and induce damage, how host cell responses to this damage and the role of DNA damage response (DDR) signals in cell fusion are still unclear. Therefore, we investigated the effect of SARS-CoV-2 spike protein on the fusion of homologous and heterologous cells expressing ACE2 in vitro models, focusing on the protein levels of ATR and ATM, the major kinases responding to DNA damage, and their substrates CHK1 and CHK2.

Identification of a gene score related to antigen processing and presentation machinery for predicting prognosis in head and neck squamous cell carcinoma and its potential implications for immunotherapy.

Background: Despite its crucial role in immune surveillance and cell survival of tumors, the significance of MHC antigen processing and presentation machinery (APM) is still not fully understood in head and neck squamous cell carcinoma (HNSCC). We sought to develop an APM gene score (APMGS) to predict prognosis and reveal the molecular and immune traits of the APMGS-defined subgroups in HNSCC.

Methods: Based on the APM-related genes acquired from 6 databases, 117 combined machine learning algorithms were applied to develop APMGS with The Cancer Genome Atlas (TCGA)-HNSCC database and validated with the Gene Expression Omnibus (GEO) dataset.

Ultra-fast [F]florbetapir PET imaging using the uMI Panorama PET/CT system.

Background: There is a need for faster amyloid PET scans to reduce patients' discomfort, minimize movement artifacts, and increase throughput. The recently introduced uMI Panorama PET/CT system featuring enhanced spatial resolution and sub-200ps TOF offers the potential for shorter scan duration without sacrificing image quality or efficacy to detect Aβ deposition. The study aims to establish a faster acquisition protocol for [F]florbetapir PET imaging using digital PET/CT scanner uMI Panorama, while ensuring adequate image quality and amyloid-β (Aβ) detectability comparable to the standard 10-minute scan.

Integrated multi-omics analysis reveals clinical significance of hepatocyte nuclear factor-1β in tumor immune microenvironment, immunotherapy and prognostic prediction for colon adenocarcinoma.

Background: Research has consistently highlighted the key role of hepatocyte nuclear factor 1β (HNF1B) in organ development and cancer, including its involvement in colon cancer via shifted-code mutations. However, the specific effects of HNF1B on cancer immunotherapy and the immune microenvironment are not fully understood. This study investigated the impact of HNF1B on colon cancer immunotherapy in depth.

A real-world pharmacovigilance analysis of potential ototoxicity associated with sacubitril/valsartan based on FDA Adverse Event Reporting System (FAERS).

Sacubitril/valsartan, a first-in-class angiotensin receptor neprilysin inhibitor, is widely used to treat heart failure. Despite its efficacy, sacubitril/valsartan inevitably causes adverse events such as hypotension, renal dysfunction, hyperkalemia, and angioedema. Sacubitril/valsartan-associated ototoxicity is often underreported in clinical studies and real-world settings.

Aldehyde Dehydrogenase 2 Lactylation Aggravates Mitochondrial Dysfunction by Disrupting PHB2 Mediated Mitophagy in Acute Kidney Injury.

Mitochondrial dysfunction is a crucial event in acute kidney injury (AKI), leading to a metabolic shift toward glycolysis and increased lactate production. Lactylation, a posttranslational modification derived from lactate, plays a significant role in various cellular processes, yet its implications in AKI remain underexplored. Here, a marked increase in lactate levels and pan-Kla levels are observed in kidney tissue from AKI patients and mice, with pronounced lactylation activity in injured proximal tubular cells identified by single-cell RNA sequencing.

Machine learning-enabled virtual screening indicates the anti-tuberculosis activity of aldoxorubicin and quarfloxin with verification by molecular docking, molecular dynamics simulations, and biological evaluations.

Drug resistance in Mycobacterium tuberculosis (Mtb) is a significant challenge in the control and treatment of tuberculosis, making efforts to combat the spread of this global health burden more difficult. To accelerate anti-tuberculosis drug discovery, repurposing clinically approved or investigational drugs for the treatment of tuberculosis by computational methods has become an attractive strategy. In this study, we developed a virtual screening workflow that combines multiple machine learning and deep learning models, and 11 576 compounds extracted from the DrugBank database were screened against Mtb.

Comparison of Embolization Coils and Patent Ductus Arteriosus Occluders for Coronary Artery Fistula Transcatheter Closure: A Single Centre Experience.

Background And Objectives: There is no dedicated occlusive device for closing coronary artery fistulas (CAFs), and specific efficacy and safety data of various off-label occlusive devices for CAFs closure are scarce.

Methods: Patients undergoing transcatheter closure of CAFs from January 2011 to December 2022 were included in the single-center retrospective study. The study population was divided into 2 groups: coils group (n=35) and patent ductus arteriosus (PDA) occluders group (n=66).

Risk of comorbidity of autoimmune liver disease in patients with inflammatory bowel disease: A single-center case-control study in China.

Objective: To investigate the prevalence of autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC), and the impact of comorbidity of AIH, PBC, and PSC on hospitalization burden in patients with inflammatory bowel disease (IBD).

Methods: Inpatients admitted to Peking Union Medical College Hospital from January 1, 1998 to December 31, 2021 were included. Odds ratio (OR) and the corresponding 95% confidence interval (CI) were calculated to compare the risk of AIH, PBC, and PSC between IBD and non-IBD patients.

Risk prediction of new-onset thrombocytopenia in patients with systemic lupus erythematosus: a multicenter prospective cohort study based on Chinese SLE treatment and research group (CSTAR) registry.

Background: Thrombocytopenia (TP) is a hematological manifestation of systemic lupus erythematosus (SLE) and is associated with unfavorable prognostic outcomes. This study aimed to develop a risk prediction model for new-onset TP in SLE patients.

Methods: Based on the multicenter prospective Chinese SLE Treatment and Research Group (CSTAR) registry, newly diagnosed SLE patients without TP at registration were enrolled.

Fractional 1064 nm Nd: YAG picosecond lasers for the treatment of traumatic scars: a retrospective study.

Traumatic scars negatively impact the patient's quality of life. Fractional 1064 nm Nd: YAG picosecond laser improves scars. However, the effect varies among individuals.

Brain tumor and mood disorders: a retrospective analysis of anxiety and depression in patients with primary and metastatic brain tumors.

Brain tumors are associated with a dismal prognosis, and the diagnosis often evokes significant psychological distress. However, the progression of emotional well-being throughout the clinical course of brain tumors remains poorly understood. This study aims to assess the prevalence of anxiety and depression in brain tumor patients and to identify the risk factors associated with postoperative emotional derangement in glioma and metastatic groups seperately.

CDUNeXt: efficient ossification segmentation with large kernel and dual cross gate attention.

Ossification of the ligamentum flavum (OLF) is the main causative factor of spinal stenosis, but how to accurately and efficiently identify the ossification region is a clinical pain point and an urgent problem to be solved. Currently, we can only rely on the doctor's subjective experience for identification, with low efficiency and large error. In this study, a deep learning method is introduced for the first time into the diagnosis of ligamentum flavum ossificans, we proposed a lightweight, automatic and efficient method for identifying ossified regions, called CDUNeXt.

Turning cold into hot: emerging strategies to fire up the tumor microenvironment.

The tumor microenvironment (TME) is a complex, highly structured, and dynamic ecosystem that plays a pivotal role in the progression of both primary and metastatic tumors. Precise assessment of the dynamic spatiotemporal features of the TME is crucial for understanding cancer evolution and designing effective therapeutic strategies. Cancer is increasingly recognized as a systemic disease, influenced not only by the TME, but also by a multitude of systemic factors, including whole-body metabolism, gut microbiome, endocrine signaling, and circadian rhythm.

Spatiotemporal single-cell roadmap of human skin wound healing.

Wound healing is vital for human health, yet the details of cellular dynamics and coordination in human wound repair remain largely unexplored. To address this, we conducted single-cell multi-omics analyses on human skin wound tissues through inflammation, proliferation, and remodeling phases of wound repair from the same individuals, monitoring the cellular and molecular dynamics of human skin wound healing at an unprecedented spatiotemporal resolution. This singular roadmap reveals the cellular architecture of the wound margin and identifies FOSL1 as a critical driver of re-epithelialization.

Exploring the Association Between Food Insecurity, Bowel Health, and All-Cause Mortality in the United States: Insights from NHANES 2005-2010.

Background And Aim: Functional gastrointestinal disorders such as chronic constipation (CC) and chronic diarrhea (CD) impose a significant burden on global healthcare resources. Food insecurity, a crucial social determinant of health, remains unclearly associated with CC and CD. We aim to explore the association between food insecurity and CC and CD, and its impact on all-cause mortality among participants with abnormal bowel health.

Pheochromocytoma in von Hippel-Lindau Disease: Clinical Features and Comparison With Sporadic Pheochromocytoma.

Objectives: Pheochromocytomas and paragangliomas (PPGLs) are manifestations of von Hippel-Lindau (VHL) disease. This study aims to describe the clinical features of PPGLs in VHL patients and the distinctions between VHL disease-related PPGLs and sporadic PPGLs.

Design, Patients And Measurements: The study included all patients with VHL disease and PPGLs treated in a single centre from 2007 to 2023.

Kidney Gastrin/CCKBR Attenuates Type 2 Diabetes Mellitus by Inhibiting SGLT2-Mediated Glucose Reabsorption through Erk/NF-κB Signaling Pathway.

Background: Both sodium-glucose cotransporters (SGLTs) and Na+/H+ exchangers (NHEs) rely on a favorable Na-electrochemical gradient. Gastrin, through the cholecystokinin B receptor (CCKBR), can induce natriuresis and diuresis by inhibiting renal NHEs activity. The present study aims to unveil the role of renal CCKBR in diabetes through SGLT2-mediated glucose reabsorption.

Clinical characteristics and survival outcomes in patients with pulmonary sarcomatoid carcinoma: a multicenter retrospective study.

Purpose: The clinicopathologic features, mutational status, immunohistochemical markers, and prognosis of Pulmonary sarcomatoid carcinoma (PSC) remain uncertain.

Methods: This study included 81 PSC and 337 lung adenocarcinomas (LUAD). Progression-free survival (PFS), overall survival (OS), and other clinical data were examined.

Intravenous immunoglobulin ameliorates doxorubicin-induced intestinal mucositis by inhibiting the Syk/PI3K/Akt axis and ferroptosis.

Background: Chemotherapy-induced mucositis (CIM) significantly impacts quality of life and reduces survival in patients treated with specific chemotherapeutic agents. However, effective clinical treatments for CIM remain limited. Intravenous immunoglobulin (IVIg), a therapeutic derived from pooled human plasma, is widely used to treat inflammatory diseases.

Morphological Characteristics Following Self-Expanding Transcatheter Heart Valve Implantation and Implications for Hypoattenuating Leaflet Thickening.

Background: Hypoattenuating leaflet thickening (HALT) following transcatheter aortic valve replacement (TAVR) may compromise valve durability, posing a significant barrier to the broader adoption of this technology among younger patients. Self-expanding valves (SEVs) are the most commonly used transcatheter heart valves (THVs) among Chinese patients with aortic stenosis. Understanding the potential mechanisms underlying HALT is, therefore, critical to guide future THV design and development.

Comparative Analysis of Central and Noncentral Degenerative Mitral Regurgitation Treated With Transcatheter Mitral Valve Edge-To-Edge Repair.

Background: Mitral valve transcatheter edge-to-edge repair (M-TEER) was initially indicated for central degenerative mitral regurgitation (DMR) lesions, but advancements in technology have enabled successful treatment in an increasing number of noncentral DMR patients.

Aims: This study aims to compare procedural outcomes and prognosis between noncentral DMR patients, outside clinical trial anatomical criteria, and central DMR patients undergoing M-TEER.

Methods: Drug-refractory moderate-to-severe DMR patients treated with M-TEER at Fuwai Hospital from January 2021 to February 2024 were retrospectively analyzed.

The inhibitory impact of various total body irradiation doses on the hematopoietic system of mice.

Irradiation with X-rays has been widely utilized in the clinical treatment of solid tumors and certain hematopoietic malignancies. However, this method fails to completely distinguish between malignant and normal cells. Prolonged or repeated exposure to radiation, whether due to occupational hazards or therapeutical interventions, can cause damage to normal tissues, particularly impacting the hematopoietic system.

Toripalimab plus chemotherapy for first line treatment of advanced non-small cell lung cancer (CHOICE-01): final OS and biomarker exploration of a randomized, double-blind, phase 3 trial.

A randomized double-blind phase 3 trial (CHOICE-01, NCT03856411) demonstrated that combining toripalimab with chemotherapy substantially improves progression-free survival (PFS) in advanced non-small cell lung cancer (NSCLC) patients without pretreatment. This study presents the prespecified final analysis of overall survival (OS) and biomarkers utilizing circulating tumor DNA (ctDNA) and tissue-based sequencing. Additionally, the analysis revealed a higher median overall survival (OS, 23.