Characteristics and Significance of Tertiary Lymphoid Structures Based on Molecular Subtypes in Endometrial Cancer.

The purpose of this study is to investigate the characteristics and significance of tertiary lymphoid structures (TLSs) in endometrial cancer (EC) based on molecular subtypes. A total of 220 patients with EC were retrospectively enrolled, including 20 with polymerase epsilon ultramutated (POLE-mut), 63 with mismatch repair deficient, 32 with p53 abnormal, and 105 with no specific molecular profile. The presence and maturity of TLSs were determined by immunohistochemical markers (CD3, CD20, CD21, and Bcl6).

Reliable imputation of spatial transcriptomes with uncertainty estimation and spatial regularization.

Imputation of missing features in spatial transcriptomics is urgently needed due to technological limitations. However, most existing computational methods suffer from moderate accuracy and cannot estimate the reliability of the imputation. To fill this research gap, we introduce a computational model, TransImpute, that imputes the missing feature modality in spatial transcriptomics by mapping it from single-cell reference data.

Mechanism of EHMT2-mediated genomic imprinting associated with Prader-Willi syndrome.

Prader-Willi Syndrome (PWS) is caused by loss of expression of paternally expressed genes in the human 15q11.2-q13 imprinting domain. A set of imprinted genes that are active on the paternal but silenced on the maternal chromosome are intricately regulated by a bipartite imprinting center (PWS-IC) located in the PWS imprinting domain.

Housekeeping U1 snRNA facilitates antiviral innate immunity by promoting TRIM25-mediated RIG-I activation.

U1 small nuclear RNA (snRNA) is an abundant and evolutionarily conserved 164-nucleotide RNA species that functions in pre-mRNA splicing, and it is considered to be a housekeeping non-coding RNA. However, the role of U1 snRNA in regulating host antiviral immunity remains largely unexplored. Here, we find that RNVU1-18, a U1 pseudogene, is significantly upregulated in the host infected with RNA viruses, including influenza and respiratory syncytial virus.

Carbonylation of Runx2 at K176 by 4-Hydroxynonenal Accelerates Vascular Calcification.

Background: Vascular calcification, which is characterized by calcium deposition in arterial walls and the osteochondrogenic differentiation of vascular smooth muscle cells, is an actively regulated process that involves complex mechanisms. Vascular calcification is associated with increased cardiovascular adverse events. The role of 4-hydroxynonenal (4-HNE), which is the most abundant stable product of lipid peroxidation, in vascular calcification has been poorly investigated.

Gastroprotective action of the extract of Corydalis yanhusuo in Helicobacter pylori infection and its bioactive component, dehydrocorydaline.

Ethnopharmacological Relevance: Helicobacter pylori (H. pylori) infection is a frequent chronic infection. Persistent infection is the strongest risk factor for developing gastric complications leading to gastric cancer.

New Insights Into Long- Versus Short-Term Dual Antiplatelet Therapy Duration in Patients After Stenting for Left Main Coronary Artery Disease: Findings From a Prospective Observational Study.

Background: The appropriate duration of dual antiplatelet therapy (DAPT) and risk-benefit ratio for long-term DAPT in patients with left main (LM) disease undergoing percutaneous coronary intervention remains uncertain.

Methods: Four thousand five hundred sixty-one consecutive patients with stenting of LM disease at a single center from January 2004 to December 2016 were enrolled. Decision to discontinue or remain on DAPT after 12 months was left to an individualized decision-making based on treating physicians by weighing the patient's risks of ischemia versus bleeding and considering patient preference.

Association Between Diabetic Retinopathy, Brain Structural Abnormalities, and Cognitive Impairment for Accumulated Evidence in Observational Studies.

Purpose: To evaluate the association between diabetic retinopathy (DR) and cerebral disease or cognitive impairment.

Design: Systematic review and meta-analysis.

Method: The hypothesis was formulated prior to data collection.

A randomised controlled trial to clinically validate follitropin delta in its individualised dosing regimen for ovarian stimulation in Asian IVF/ICSI patients.

Study Question: Is ovarian stimulation with follitropin delta in its individualised fixed-dose regimen at least as efficacious as follitropin alfa in a conventional dosing regimen in Asian population?

Summary Answer: Ovarian stimulation with individualised follitropin delta dosing resulted in a non-inferior ongoing pregnancy rate, a significantly higher live birth rate and a significantly lower incidence of early ovarian hyperstimulation syndrome (OHSS) and/or preventive interventions compared to conventional follitropin alfa dosing.

What Is Known Already: Previous randomised controlled trials conducted in Japan as well as in Europe, North- and South America have demonstrated that ovarian stimulation with the individualised follitropin delta dosing regimen based on serum anti-Müllerian hormone (AMH) level and body weight modulated the ovarian response and reduced the risk of OHSS without compromising pregnancy and live birth rates.

Study Design, Size, Duration: Randomised, controlled, multi-centre, assessor-blind trial conducted in 1009 Asian patients from mainland China, South Korea, Vietnam and Taiwan, undergoing their first IVF/ICSI cycle.

Radiologic and Pathological Investigation of Pseudarthrosis in Ankylosing Spondylitis: Distinguishing Between Inflammatory and Traumatic Etiology.

Objective: To investigate the pathogenesis of pseudarthrosis in ankylosing spondylitis (AS) based on the pathological analysis of specimens harvested during surgery.

Methods: Radiographic and clinical data for 17 consecutive AS patients with pseudarthrosis were retrospectively analyzed. Meanwhile, the pathological analysis of specimens obtained during surgery was also performed.

Randomized Comparisons of Double-Dose Clopidogrel or Adjunctive Cilostazol Versus Standard Dual Antiplatelet in Patients With High Posttreatment Platelet Reactivity: Results of the CREATIVE Trial.

Background: Patients undergoing percutaneous coronary intervention react differently to antiplatelet drugs. Those with low responsiveness to clopidogrel have a higher risk of cardiac ischemic events. The goal of this study is to conduct a head-to-head comparison of the safety and effectiveness of intensified antiplatelet therapies (either double-dose clopidogrel [DOUBLE] or adjunctive cilostazol [TRIPLE]) and conventional strategy (STANDARD) in patients after percutaneous coronary intervention.

DKK3 (Dickkopf 3) Alters Atherosclerotic Plaque Phenotype Involving Vascular Progenitor and Fibroblast Differentiation Into Smooth Muscle Cells.

Objective: DKK3 (dickkopf 3), a 36-kD secreted glycoprotein, has been shown to be involved in the differentiation of partially reprogrammed cells and embryonic stem cells to smooth muscle cells (SMCs), but little is known about its involvement in vascular disease. This study aims to assess the effects of DKK3 on atherosclerotic plaque composition.

Approach And Results: In the present study, we used a murine model of atherosclerosis () in conjunction with and performed tandem stenosis of the carotid artery to evaluate atherosclerotic plaque development.

Diagnostic value of joint detection of homocysteine and RDW CV on acute myocardial infarction.

The article "Diagnostic value of joint detection of homocysteine and RDW CV on acute myocardial infarction" by G.-X. Hu, J.

Valproic acid-mediated myocardial protection of acute hemorrhagic rat via the BCL-2 pathway.

Background: Hemorrhage is a major cause of morbidity and mortality among trauma patients. The pathophysiologic changes following acute severe hemorrhage and tissue hypoxia lead to an imbalance of protein acetylation. Histone deacetylase inhibitors (HDACIs) were reported to restore the acetylation imbalance and serve as potential drugs for treating severe hemorrhage.

Unique Expression of Angiotensin Type-2 Receptor in Sex-Specific Distribution of Myelinated Ah-Type Baroreceptor Neuron Contributing to Sex-Dimorphic Neurocontrol of Circulation.

This study aims to understand the special expression patterns of angiotensin-II receptor (AT1R and AT2R) in nodose ganglia and nucleus of tractus solitary of baroreflex afferent pathway and their contribution in sex difference of neurocontrol of blood pressure regulation. In this regard, action potentials were recorded in baroreceptor neurons (BRNs) using whole-cell patch techniques; mRNA and protein expression of AT1R and AT2R in nodose ganglia and nucleus of tractus solitary were evaluated using real time-polymerase chain reaction, Western blot, and immunohistochemistry at both tissue and single-cell levels. The in vivo effects of 17β-estradiol on blood pressure and AT2R expression were also tested.

MiR-138 exerts anti-glioma efficacy by targeting immune checkpoints.

Background: Antibody therapeutic targeting of the immune checkpoints cytotoxic T-lymphocyte-associated molecule 4 (CTLA-4) and programmed cell death 1 (PD-1) has demonstrated marked tumor regression in clinical trials. MicroRNAs (miRNAs) can modulate multiple gene transcripts including possibly more than one immune checkpoint and could be exploited as immune therapeutics.

Methods: Using online miRNA targeting prediction algorithms, we searched for miRNAs that were predicted to target both PD-1 and CTLA-4.

Up-regulated expression of WNT5a increases inflammation and oxidative stress via PI3K/AKT/NF-κB signaling in the granulosa cells of PCOS patients.

Context: Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine disorder accompanied by chronic low-grade inflammation, but the molecular mechanism remains unclear.

Objective: We investigated the action of WNT5a in the development of chronic inflammation in PCOS and the related molecular signaling pathways.

Design And Setting: This was a prospective study conducted at the Division of Reproduction Center, Peking University Third Hospital.

Genetic dissection of tie pathway in mouse lymphatic maturation and valve development.

Objective: The genetic program underlying lymphatic development is still incompletely understood. This study aims to dissect the role of receptor tyrosine kinase with immunoglobulin-like and EGF (epidermal growth factor)-like domains 1 (Tie1) and Tie2 in lymphatic formation using genetically modified mouse models.

Approach And Results: We generated conditional knockout mouse models targeting Tie1, Tie2, and angiopoietin-2 in this study.

Sequence analysis of the prion protein gene in Mongolian gazelles (Procapra gutturosa).

Prion diseases are a group of human and animal neurodegenerative conditions, which are caused by the deposition of an abnormal isoform prion protein (PrPSc) encoded by a single copy prion protein gene (Prnp). In sheep, genetic variations of Prnp were found to be associated with the incubation period, susceptibility, and species barrier to the scrapie disease. We investigated the sequence and polymorphisms of the prion protein gene of Mongolian gazelles (gPrnp).