High clinical utility of long-read sequencing for precise diagnosis of congenital adrenal hyperplasia in 322 probands.

Background: The molecular genetic diagnosis of congenital adrenal hyperplasia (CAH) is very challenging due to the high homology between the CYP21A2 gene and its pseudogene CYP21A1P.

Methodology: This study aims to assess the clinical efficacy of targeted long-read sequencing (T-LRS) by comparing it with a control method based on the combined assay (NGS, Multiplex ligation-dependent probe amplification and Sanger sequencing) and to introduce T-LRS as a first-tier diagnostic test for suspected CAH patients to improve the precise diagnosis of CAH.

Results: A large cohort of 562 participants including 322 probands and 240 family members was enrolled for the perspective (96 probands) and prospective study (226 probands).

Construction of a prognostic model for gastric cancer based on immune infiltration and microenvironment, and exploration of MEF2C gene function.

Background: Advanced gastric cancer (GC) exhibits a high recurrence rate and a dismal prognosis. Myocyte enhancer factor 2c (MEF2C) was found to contribute to the development of various types of cancer. Therefore, our aim is to develop a prognostic model that predicts the prognosis of GC patients and initially explore the role of MEF2C in immunotherapy for GC.

Single-cell transcriptomics unveils multifaceted immune heterogeneity in early-onset versus late-onset cervical cancer.

Early-onset (EOCC) and late-onset cervical cancers (LOCC) represent two clinically distinct subtypes, each defined by unique clinical manifestations and therapeutic responses. However, their immunological profiles remain poorly explored. Herein, we analyzed single-cell transcriptomic data from 4 EOCC and 4 LOCC samples to compare their immune architectures.

Association of iron deficiency with kidney outcome and all-cause mortality in chronic kidney disease patients without anemia.

Background: Iron deficiency is prevalent in patients with chronic kidney disease (CKD), even in those without anemia. However, the effects of iron deficiency on CKD progression and all-cause mortality in non-dialysis-dependent CKD (NDD-CKD) patients without anemia remain incompletely understood.

Methods: This multicenter retrospective nationwide cohort study included adult patients with non-anemia NDD-CKD from 24 hospitals across China.

Nonacademic predictors of China medical licensing examination.

Background: National Medical Licensing Examination (NMLE) is the entrance exam for medical practice in China, and its general medical knowledge test (GMKT) evaluates abilities of medical students to comprehensively apply medical knowledge to clinical practice. This study aimed to identify nonacademic predictors of GMKT performance, which would benefit medical schools in designing appropriate strategies and techniques to facilitate the transition from medical students to qualified medical practitioners.

Methods: In 1202 medical students, we conducted the deletion-substitution-addition (DSA) and structural equation model (SEM) analyses to identify nonacademic predictors of GMKT performance from 98 candidate variables including early life events, physical conditions, psychological and personality assessments, cognitive abilities, and socioeconomic conditions.

Evaluation of Inflammatory Activity of Extraocular Muscles in Thyroid Associated Orbitopathy by [Ga]DOTATATE PET/CT.

Purpose: The accurate assessment of inflammatory activity of the extraocular muscles (EOMs) in thyroid associated ophthalmopathy (TAO) is crucial for formulating subsequent treatment strategies and prognostic judgments. This study aims to explore the efficacy of using [Ga]DOTATATE PET/CT to assess the inflammatory activity of EOMs in TAO patients.

Procedures: This study enrolled 22 TAO patients and 6 healthy volunteers, all of whom underwent orbital [Ga]DOTATATE PET/CT.

Shenmai Injection Reduces Cardiomyocyte Apoptosis Induced by Doxorubicin through miR-30a/Bcl-2.

Objective: To explore the molecular mechanism of Shenmai Injection (SMI) against doxorubicin (DOX) induced cardiomyocyte apoptosis.

Methods: A total of 40 specific pathogen-free (SPF) male Sprague Dawley (SD) male rats were divided into 5 groups based on the random number table, including the control group, the model group, miR-30a agomir group, SMI low-dose (SMI-L) group, and SMI high-dose (SMI-H) group, with 8 rats in each group. Except for the control group, the rats were injected weekly with DOX (2 mg/kg) in the tail vein for 4 weeks to induce myocardial injury, and were given different regimens of continuous intervention for 2 weeks.

Helicobacter pylori CagA promotes gastric cancer immune escape by upregulating SQLE.

Helicobacter pylori (H. pylori) infection is a well-established risk factor for gastric cancer, primarily due to its virulence factor, cytotoxin-associated gene A (CagA). Although PD-L1/PD-1-mediated immune evasion is critical in cancer development, the impact of CagA on PD-L1 regulation remains unclear.

Decreased risk of cardiovascular disease mortality associated with occasional positive screens following cancer screenings.

Positive results from cancer screenings, like a cancer diagnosis, can increase the risk of cardiovascular disease (CVD) mortality due to heightened psychological stress. However, positive screening results may also serve as a teachable moment to encourage the adoption of a healthier lifestyle. Consequently, the overall association between positive screenings and CVD mortality risk remains unclear.

The prognostic value of anti-gp210 and anti-centromere antibodies in patients with primary biliary cholangitis: Enhancing the prognostic utility on the GLOBE scoring system.

Background: Positivity for anti-gp210 and anti-centromeric antibodies (ACA) in patients with primary biliary cholangitis (PBC) have been associated with the progression of liver failure and portal hypertension (PH), respectively. The value of combining risk autoantibody assessments with prognostic scoring systems in improving risk assessment in patients with PBC remains unclear.

Aims: To investigate the prognostic significance of various combinations of anti-gp210 and ACA statuses and their enhancing the prognostic utility on the GLOBE scoring system.

Effect of free gingival graft dimension on postsurgical shrinkage in posterior implant placement: A prospective parallel cohort study.

Statement Of Problem: The impact of free gingival graft (FGG) dimensions on the postsurgical shrinkage of keratinized tissue width (KTW) and surface area in posterior implant sites is unclear. Standardized assessments of how graft dimensions influence KTW and surface area shrinkage rates over a 6-month period after FGG are lacking.

Purpose: The purpose of this prospective parallel cohort study was to examine the impact of the graft dimensions on the postsurgical shrinkage of KTW and surface area over a 6-month follow-up period after FGG in the posterior regions.

Health Impacts of PM Emissions from Brake Pad Wear: A Comprehensive Study on Pulmonary, Metabolic, and Microbiota Alterations.

The environmental impact of harmful particles from tire and brake systems is a growing concern. This study investigated the health impacts of PM emissions from brake pad wear on adult C57BL/6 mice. The mice were exposed to brake pad particles via intratracheal infusion, and various health parameters were assessed.

Gut microbial GABA imbalance emerges as a metabolic signature in mild autism spectrum disorder linked to overrepresented Escherichia.

Gut microbiota (GM) alterations have been implicated in autism spectrum disorder (ASD), yet the specific functional architecture remains elusive. Here, employing multi-omics approaches, we investigate stool samples from two distinct cohorts comprising 203 children with mild ASD or typical development. In our screening cohort, regression-based analysis for metabolomic profiling identifies an elevated γ-aminobutyric acid (GABA) to glutamate (Glu) ratio as a metabolic signature of ASD, independent of age and gender.

High cellular plasticity state of medulloblastoma local recurrence and distant dissemination.

Medulloblastoma (MB), a heterogeneous pediatric brain tumor, poses challenges in the treatment of tumor recurrence and dissemination. To characterize cellular diversity and genetic features, we comprehensively analyzed single-cell/nucleus RNA sequencing (sc/snRNA-seq), single-nucleus assay for transposase-accessible chromatin sequencing (snATAC-seq), and spatial transcriptomics profiles and identified distinct cellular populations in SHH (sonic hedgehog) and Group_3 subgroups, with varying proportions in local recurrence or dissemination. Local recurrence showed higher cycling tumor cell enrichment, whereas disseminated lesions had a relatively notable presence of differentiated subsets.

Supported Mindfulness-Based Self-Help Intervention as an Adjunctive Treatment for Rapid Symptom Change in Emotional Disorders: A Practice-Oriented Multicenter Randomized Controlled Trial.

Introduction: Rapid symptom relief is crucial for individuals with emotional disorders. The current study aimed to determine whether facilitator-supported mindfulness-based self-help (MBSH) intervention as an adjunctive treatment could provide rapid improvement for individuals with emotional disorders.

Methods: A practice-oriented randomized controlled trial was conducted on a sample of 302 patients with emotional disorders from four centers.

Causal associations between telomere length and pulmonary arterial hypertension: A two-sample Mendelian randomization study.

Pulmonary arterial hypertension (PAH) is a life-threatening condition characterized by elevated pulmonary artery pressure, leading to right heart failure, and mortality. The role of telomere length, a marker of biological aging, in PAH remains unclear. We utilized summary-level data from genome-wide association studies for various measures of telomere length and PAH.

Impaired lipid homeostasis and elevated lipid oxidation of erythrocyte membrane in adolescent depression.

Adolescent depression is a globally concerned mental health issue, the pathophysiological mechanisms of which remain elusive. Membrane lipids play a crucial role in brain development and function, potentially serving as a crossroad for the abnormalities in neurotransmitters, neuroendocrine, inflammation, oxidative stress, and energy metabolism observed in depressed adolescents. The primary aim of this study was to investigate the erythrocyte membrane lipid profile in adolescent depression.

PADS-Net: GAN-based radiomics using multi-task network of denoising and segmentation for ultrasonic diagnosis of Parkinson disease.

Parkinson disease (PD) is a prevalent neurodegenerative disorder, and its accurate diagnosis is crucial for timely intervention. We propose the PArkinson disease Denoising and Segmentation Network (PADS-Net), to simultaneously denoise and segment transcranial ultrasound images of midbrain for accurate PD diagnosis. The PADS-Net is built upon generative adversarial networks and incorporates a multi-task deep learning framework aimed at optimizing the tasks of denoising and segmentation for ultrasound images.

Construction and characterization of chimeric FcγR T cells for universal T cell therapy.

Background: Several approaches are being explored for engineering off-the-shelf chimeric antigen receptor (CAR) T cells. In this study, we engineered chimeric Fcγ receptor (FcγR) T cells and tested their potential as a versatile platform for universal T cell therapy.

Methods: Chimeric FcγR (CFR) constructs were generated using three distinct forms of FcγR, namely CD16A, CD32A, and CD64.

The SIRT5-JIP4 interaction promotes osteoclastogenesis by modulating RANKL-induced signaling transduction.

Receptor activator of nuclear factor kappa-B ligand (RANKL) initiates a complex signaling cascade that is crucial for inducing osteoclast differentiation and activation. RANKL-induced signaling has been analyzed in detail, and the involvement of TNF receptor-associated factor 6 (TRAF6), calmodulin-dependent protein kinase (CaMK), NF-κB, mitogen-activated protein kinase (MAPK), activator protein-1 (AP-1), and molecules that contain an immunoreceptor tyrosine-based activation motif (ITAM) has been reported. However, the precise molecular steps that regulate RANKL signaling remain largely unknown.

Establishment and internal validation of a model to predict the efficacy of Adalimumab in Crohn's disease.

Background: Clinically, the ability to distinguish which Crohn's disease patients can benefit from Adalimumab is limited.

Aims: This study aimed to develop a model for predicting clinical remission probability for Crohn's disease patients with Adalimumab at 12 weeks. The model assists clinicians in identifying which Crohn's disease patients are likely to benefit from Adalimumab treatment before starting therapy, thus optimizing individualized treatment strategies.

Allelic transcriptomic profiling identifies the role of PRD-like homeobox genes in human embryonic-cleavage-stage arrest.

Cleavage-stage arrest in human embryos substantially limits the success rate of infertility treatment, with maternal-to-zygotic transition (MZT) abnormalities being a potential contributor. However, the underlying mechanisms and regulators remain unclear. Here, by performing allelic transcriptome analysis on human preimplantation embryos, we accurately quantified MZT progression by allelic ratio and identified a fraction of 8-cell embryos, at the appropriate developmental time point and exhibiting normal morphology, were in transcriptionally arrested status.

SHMT2 regulates CD8+ T cell senescence via the reactive oxygen species axis in HIV-1 infected patients on antiretroviral therapy.

Background: Although antiretroviral therapy (ART) effectively inhibits viral replication, it does not fully mitigate the immunosenescence instigated by HIV infection. Cellular metabolism regulates cellular differentiation, survival, and senescence. Serine hydroxymethyltransferase 2 (SHMT2) is the first key enzyme for the entry of serine into the mitochondria from the de novo synthesis pathway that orchestrates its conversion glutathione (GSH), a key molecule in neutralising ROS and ensuring the stability of the immune system.