Enforced activation of the CREB/KDM2B axis prevents alcohol-induced embryonic developmental delay.

Unintentional, early pregnancy alcohol consumption affects embryonic development. During the peri-implantation stage, coinciding with the transition from naive to primed pluripotency, the long isoform of KDM2B (KDM2BLF) underlies the de novo establishment of polycomb repressive complex (PRC) functions at promoters after fertilization. However, it remains unclear whether and how ethanol exposure affects this spatiotemporal chromatin setting.

Changes in the Objective Vision Quality of Adolescents in a Mesopic Visual Environment After Wearing Orthokeratology Lenses: A Prospective Study.

Purpose: This study aimed to investigate changes in objective vision quality in mesopic environments in teenagers with myopia after wearing orthokeratology (OK) lenses.

Methods: This prospective clinical study included 45 patients (80 eyes) who received OK lenses at the First Affiliated Hospital of Jinan University from March 2021 to September 2021. An Optical Path Difference-Scan III refractive power/corneal analyzer was used to determine the corneal topographic parameters (corneal e, corneal Q, surface asymmetry index (SAI), and surface regularity index (SRI)), higher-order aberrations (HOAs), axial length (AL) change, lens decentration, induced astigmatism, target power, and Strehl ratio (SR) in a mesopic visual environment after wearing OK lenses for 6 months.

Lung tumor discrimination by deep neural network model CanDo via DNA methylation in bronchial lavage.

Bronchoscopic-assisted discrimination of lung tumors presents challenges, especially in cases with contraindications or inaccessible lesions. Through meta-analysis and validation using the HumanMethylation450 database, this study identified methylation markers for molecular discrimination in lung tumors and designed a sequencing panel. DNA samples from 118 bronchial washing fluid (BWF) specimens underwent enrichment via multiplex PCR before targeted methylation sequencing.

Postprocedural Anticoagulation After Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction: A Multicenter, Randomized, Double-Blind Trial.

Background: Postprocedural anticoagulation (PPA) is frequently administered after primary percutaneous coronary intervention in ST-segment-elevation myocardial infarction, although no conclusive data support this practice.

Methods: The RIGHT trial (Comparison of Anticoagulation Prolongation vs no Anticoagulation in STEMI Patients After Primary PCI) was an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled, superiority trial conducted at 53 centers in China. Patients with ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention were randomly assigned by center to receive low-dose PPA or matching placebo for at least 48 hours.

Single Bolus r-SAK Before Primary PCI for ST-Segment-Elevation Myocardial Infarction.

Background: It is uncertain whether adjunctive thrombolysis is beneficial for patients with ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention (PCI) within 120 minutes of presentation. This study was to determine whether in patients presenting with ST-segment-elevation myocardial infarction a single bolus recombinant staphylokinase (r-SAK) before timely PCI leads to improved patency of the infarct-related artery and reduces the infarct size.

Methods: This is an open-label, prospective, multicenter, randomized study.

Toward Precision Medicine: Circadian Rhythm of Blood Pressure and Chronotherapy for Hypertension - 2021 NHLBI Workshop Report.

Healthy individuals exhibit blood pressure variation over a 24-hour period with higher blood pressure during wakefulness and lower blood pressure during sleep. Loss or disruption of the blood pressure circadian rhythm has been linked to adverse health outcomes, for example, cardiovascular disease, dementia, and chronic kidney disease. However, the current diagnostic and therapeutic approaches lack sufficient attention to the circadian rhythmicity of blood pressure.

MRI-based Texture Analysis of Infrapatellar Fat Pad to Predict Knee Osteoarthritis Incidence.

Background Infrapatellar fat pad (IPFP) quality has been implicated as a marker for predicting knee osteoarthritis (KOA); however, no valid quantification for subtle IPFP abnormalities has been established. Purpose To investigate whether MRI-based three-dimensional texture analysis of IPFP abnormalities could help predict incident radiographic KOA. Materials and Methods In this prospective nested case-control study, 690 participants whose knees were at risk for KOA were included from the Pivotal Osteoarthritis Initiative MRI Analyses incident osteoarthritis cohort.

pH-Responsive Polymer Nanoparticles for Efficient Delivery of Cas9 Ribonucleoprotein With or Without Donor DNA.

Clustered regularly interspaced short palindromic repeat (CRISPR)-associated protein 9 (Cas9) may offer new therapeutics for genetic diseases through gene disruption via nonhomologous end joining (NHEJ) or gene correction via homology-directed repair (HDR). However, clinical translation of CRISPR technology is limited by the lack of safe and efficient delivery systems. Here, facilely fabricated pH-responsive polymer nanoparticles capable of safely and efficiently delivering Cas9 ribonucleoprotein alone (termed NHEJ-NP, diameter = 29.

Contemporary Update of Retinoblastoma in China: Three-Decade Changes in Epidemiology, Clinical Features, Treatments, and Outcomes.

Purpose: To report three-decade changes of clinical characteristics, progress of treatments, and risk factors associated with mortality and enucleation in patients with retinoblastoma in China.

Design: Retrospective cohort study.

Methods: This multicenter study included 2552 patients diagnosed with retinoblastoma in 38 medical centers in 31 provinces in China from 1989 to 2017, with follow-up data.

Chimeric antigen receptor natural killer (CAR-NK) cell design and engineering for cancer therapy.

Due to their efficient recognition and lysis of malignant cells, natural killer (NK) cells are considered as specialized immune cells that can be genetically modified to obtain capable effector cells for adoptive cellular treatment of cancer patients. However, biological and technical hurdles related to gene delivery into NK cells have dramatically restrained progress. Recent technological advancements, including improved cell expansion techniques, chimeric antigen receptors (CAR), CRISPR/Cas9 gene editing and enhanced viral transduction and electroporation, have endowed comprehensive generation and characterization of genetically modified NK cells.

A Trial of Lopinavir-Ritonavir in Adults Hospitalized with Severe Covid-19.

Background: No therapeutics have yet been proven effective for the treatment of severe illness caused by SARS-CoV-2.

Methods: We conducted a randomized, controlled, open-label trial involving hospitalized adult patients with confirmed SARS-CoV-2 infection, which causes the respiratory illness Covid-19, and an oxygen saturation (Sao) of 94% or less while they were breathing ambient air or a ratio of the partial pressure of oxygen (Pao) to the fraction of inspired oxygen (Fio) of less than 300 mm Hg. Patients were randomly assigned in a 1:1 ratio to receive either lopinavir-ritonavir (400 mg and 100 mg, respectively) twice a day for 14 days, in addition to standard care, or standard care alone.

Effects of Mobile Text Messaging on Glycemic Control in Patients With Coronary Heart Disease and Diabetes Mellitus: A Randomized Clinical Trial.

Background: Mobile health interventions may support risk factor management and are readily scalable in healthcare systems. We aim to evaluate the efficacy of a text messaging-based intervention to improve glycemic control in patients with coronary heart disease and diabetes mellitus in China.

Methods And Results: The CHAT-DM study (Cardiovascular Health and Texting-Diabetes Mellitus) was a parallel-group, single-blind, randomized clinical trial that included 502 patients with both coronary heart disease and diabetes mellitus from 34 hospitals in China.

One-Step Growth of Spatially Graded MoW S Monolayers with a Wide Span in Composition (from x = 0 to 1) at a Large Scale.

Alloying is an effective way to modulate material's properties. In particular, graded alloying within a single domain of two-dimensional transition-metal chalcogenide (2D-TMC) is of great technological importance, for example, for achieving band gap modulations. Here, we report a facile method to grow gradient alloying of MoW S monolayers with large domain sizes and high crystal qualities via the chemical vapor deposition technique.

Patient-Specific and Gene-Corrected Induced Pluripotent Stem Cell-Derived Cardiomyocytes Elucidate Single-Cell Phenotype of Short QT Syndrome.

Rationale: Short QT syndrome (SQT) is a rare but arrhythmogenic disorder featured by shortened ventricular repolarization and a propensity toward life-threatening ventricular arrhythmias and sudden cardiac death.

Objective: This study aimed to investigate the single-cell mechanism of SQT using patient-specific and gene-corrected induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs).

Methods And Results: One SQT patient carrying missense mutation T618I in potassium voltage-gated channel subfamily H member 2 ( KCNH2) was recruited as well as 2 healthy control subjects in this study.

Molybdenum-Tungsten Mixed Oxide Deposited into Titanium Dioxide Nanotube Arrays for Ultrahigh Rate Supercapacitors.

A novel method involving the fabrication of Mo-W mixed oxide (MoWO) is proposed to modify the modest reaction kinetics and poor cycling stability of MoO material. By a simple coelectrodeposition method, a series of MoWO oxides is deposited on a TiO nanotube array substrate. Because of the differences between Mo and W in nature, there is significant distortion existing in the mixed oxides, leading to their decreased crystallite size and enlarged lattice space, which facilitates ion diffusion in the solid.

Cortical Thickness of Native Tibetans in the Qinghai-Tibetan Plateau.

Background And Purpose: High-altitude environmental factors and genetic variants together could have exerted their effects on the human brain. The present study was designed to investigate the cerebral morphology in high-altitude native Tibetans.

Materials And Methods: T1-weighted brain images were obtained from 77 Tibetan adolescents on the Qinghai-Tibetan Plateau (altitude, 2300-5300 m) and 80 matched Han controls living at sea level.

Anatomic Insights into Disrupted Small-World Networks in Pediatric Posttraumatic Stress Disorder.

Purpose To use diffusion-tensor (DT) imaging and graph theory approaches to explore the brain structural connectome in pediatric posttraumatic stress disorder (PTSD). Materials and Methods This study was approved by the relevant research ethics committee, and all participants' parents or guardians provided informed consent. Twenty-four pediatric patients with PTSD and 23 control subjects exposed to trauma but without PTSD were recruited after the 2008 Sichuan earthquake.

Toll-Like Receptor 4/MyD88-Mediated Signaling of Hepcidin Expression Causing Brain Iron Accumulation, Oxidative Injury, and Cognitive Impairment After Intracerebral Hemorrhage.

Background: Disturbance of brain iron metabolism after intracerebral hemorrhage (ICH) results in oxidative brain injury and cognition impairment. Hepcidin plays an important role in regulating iron metabolism, and we have reported that serum hepcidin is positively correlated with poor outcomes in patients with ICH. However, the roles of hepcidin in brain iron metabolism after ICH remain largely unknown.

Cardiac-Specific EPI64C Blunts Pressure Overload-Induced Cardiac Hypertrophy.

The calcium-responsive molecule, calcineurin, has been well characterized to play a causal role in pathological cardiac hypertrophy over the past decade. However, the intrinsic negative regulation of calcineurin signaling during the progression of cardiomyocyte hypertrophy remains enigmatic. Herein, we explored the role of EPI64C, a dual inhibitor of both Ras and calcineurin signaling during T-cell activation, in pressure overload-induced cardiac hypertrophy.

How best to obtain consent to thrombolysis: Individualized decision-making.

Objective: To investigate the factors that influence the preferences of patients and their proxies concerning thrombolytic therapy and to determine how best to convey information.

Methods: A total of 613 participants were randomly assigned to a positively or negatively framed group. Each participant completed a series of surveys.

Real-time effects of centrotemporal spikes on cognition in rolandic epilepsy: An EEG-fMRI study.

Objective: To identify the real-time effects of interictal rolandic spikes (or centrotemporal spikes [CTS]) on language, behavior, and cognitive function in patients with rolandic epilepsy (RE).

Methods: We studied 22 medication-naive patients with RE using EEG-fMRI with a 3T MRI scanner. We used simultaneous EEG to define the pre-CTS, CTS, and post-CTS periods.

Overexpression of Nitric Oxide Synthase Restores Circulating Angiogenic Cell Function in Patients With Coronary Artery Disease: Implications for Autologous Cell Therapy for Myocardial Infarction.

Background: Circulating angiogenic cells (CACs) are peripheral blood cells whose functional capacity inversely correlates with cardiovascular risk and that have therapeutic benefits in animal models of cardiovascular disease. However, donor age and disease state influence the efficacy of autologous cell therapy. We sought to determine whether age or coronary artery disease (CAD) impairs the therapeutic potential of CACs for myocardial infarction (MI) and whether the use of ex vivo gene therapy to overexpress endothelial nitric oxide (NO) synthase (eNOS) overcomes these defects.