Chronic Active Epstein-Barr Virus Myopathy Mimicking Idiopathic Inflammatory Myopathies: A Diagnostic Pitfall, Differentiating Features, and Clinical Impact Revealed in the 10-year Case Series.

Systemic chronic active Epstein-Barr virus disease (sCAEBVD) can primarily involve skeletal muscle to form CAEBV-myopathy (CAEBV-M), which may resemble idiopathic inflammatory myopathies (IIMs). This study reports an 11-patient, 10-year cohort of CAEBV-M to summarize clinicoseropathologic features. CAEBV-M typically affects young adults (median: 29 years), with universal limb swelling, frequent disseminated muscle involvement (73%), and systemic symptoms like fever (82%), splenomegaly (82%), and hemophagocytic lymphohistiocytosis (55%).

Focal Adhesion Kinase Drives Rho/ROCK and mTOR Signaling to Protect and Augment Aortic Dissections.

Dysfunctional mechanosensing via focal adhesions (FAs) significantly contributes to thoracic aortic dissection in the β-aminopropionitrile mouse model by triggering FA kinase activation and subsequent Rho/ROCK and mTOR signaling pathways. The present findings indicate that these signaling pathways play distinct roles in ascending vs descending dissections. Specifically, in the ascending aorta, smooth muscle cell FA kinase-Rho/ROCK signaling acts as a beneficial adaptive mechanism to prevent dissections, whereas mTOR signaling is pathogenic and contributes to dissections.

Inducing hypertension in mice triggers aortic dissections with increased focal adhesion kinase signaling.

Objective: We sought to determine if hypertension in combination with a "variant of uncertain significance" that disrupts protein function, p.Arg247Cys, would induce aortic dissections in a mouse model.

Approach And Results: Administration of L-NAME via drinking water and a high salt diet increased blood pressure in WT and mice and triggered type A dissections with cardiac tamponade in 20% of the mice.

Nuclear Smooth Muscle α-actin Participates in Vascular Smooth Muscle Cell Differentiation.

Missense variants throughout , encoding smooth muscle α-actin (αSMA), predispose to adult-onset thoracic aortic disease, but variants disrupting arginine 179 (R179) lead to Smooth Muscle Dysfunction Syndrome (SMDS) characterized by diverse childhood-onset vascular diseases. Here we show that αSMA localizes to the nucleus in wildtype (WT) smooth muscle cells (SMCs), enriches in the nucleus with SMC differentiation, and associates with chromatin remodeling complexes and SMC contractile gene promotors. The p.

SMYD3 promotes endometrial cancer through epigenetic regulation of LIG4/XRCC4/XLF complex in non-homologous end joining repair.

Endometrial cancer (EC) stands as one of the most prevalent malignancies affecting the female genital tract, witnessing a rapid surge in incidence globally. Despite the well-established association of histone methyltransferase SMYD3 with the development and progression of various cancers, its specific oncogenic role in endometrial cancer remains unexplored. In the present study, we report that the expression level of SMYD3 is significantly upregulated in EC samples and associated with EC progression.

Pericentrin deficiency in smooth muscle cells augments atherosclerosis through HSF1-driven cholesterol biosynthesis and PERK activation.

Microcephalic osteodysplastic primordial dwarfism type II (MOPDII) is caused by biallelic loss-of-function variants in pericentrin (PCNT), and premature coronary artery disease (CAD) is a complication of the syndrome. Histopathology of coronary arteries from patients with MOPDII who died of CAD in their 20s showed extensive atherosclerosis. Hyperlipidemic mice with smooth muscle cell-specific (SMC-specific) Pcnt deficiency (PcntSMC-/-) exhibited significantly greater atherosclerotic plaque burden compared with similarly treated littermate controls despite similar serum lipid levels.

Smooth muscle α-actin missense variant promotes atherosclerosis through modulation of intracellular cholesterol in smooth muscle cells.

Aims: The variant p.Arg149Cys in ACTA2, which encodes smooth muscle cell (SMC)-specific α-actin, predisposes to thoracic aortic disease and early onset coronary artery disease in individuals without cardiovascular risk factors. This study investigated how this variant drives increased atherosclerosis.

Nuclear Smooth Muscle α-actin in Vascular Smooth Muscle Cell Differentiation.

Missense variants throughout , encoding smooth muscle α-actin (αSMA), predispose to adult onset thoracic aortic disease, but variants disrupting arginine 179 (R179) lead to Smooth Muscle Dysfunction Syndrome (SMDS) characterized by childhood-onset diverse vascular diseases. Our data indicate that αSMA localizes to the nucleus in wildtype (WT) smooth muscle cells (SMCs), enriches in the nucleus with SMC differentiation, and associates with chromatin remodeling complexes and SMC contractile gene promotors, and the p.R179 variant decreases nuclear localization of αSMA.

Preventing Cholesterol-Induced Perk (Protein Kinase RNA-Like Endoplasmic Reticulum Kinase) Signaling in Smooth Muscle Cells Blocks Atherosclerotic Plaque Formation.

Background: Vascular smooth muscle cells (SMCs) undergo complex phenotypic modulation with atherosclerotic plaque formation in hyperlipidemic mice, which is characterized by de-differentiation and heterogeneous increases in the expression of macrophage, fibroblast, osteogenic, and stem cell markers. An increase of cellular cholesterol in SMCs triggers similar phenotypic changes in vitro with exposure to free cholesterol due to cholesterol entering the endoplasmic reticulum, triggering endoplasmic reticulum stress and activating Perk (protein kinase RNA-like endoplasmic reticulum kinase) signaling.

Methods: We generated an SMC-specific knockout mouse model, induced hyperlipidemia in the mice by AAV- injection, and subjected them to a high-fat diet.

Integrated genomic profiling and modelling for risk stratification in patients with advanced oesophagogastric adenocarcinoma.

Objective: Prognosis of patients with advanced oesophagogastric adenocarcinoma (mEGAC) is poor and molecular determinants of shorter or longer overall survivors are lacking. Our objective was to identify molecular features and develop a prognostic model by profiling the genomic features of patients with mEGAC with widely varying outcomes.

Design: We profiled 40 untreated mEGACs (20 shorter survivors <13 months and 20 longer survivors >36 months) with whole-exome sequencing (WES) and RNA sequencing and performed an integrated analysis of exome, transcriptome, immune profile and pathological phenotypes to identify the molecular determinants, developing an integrated model for prognosis and comparison with The Cancer Genome Atlas (TCGA) cohorts.

Comparison of Systemic EBV-positive T-Cell and NK-Cell Lymphoproliferative Diseases of Childhood Based on Classification Evolution: New Classification, Old Problems.

Systemic Epstein-Barr virus-positive T-cell and natural killer (NK)-cell lymphoproliferative diseases of childhood are a group of lethal diseases mostly affecting children and young adults. The Ohshima Grading System and the 2017 World Health Organization (WHO) classification have been used for classifying this spectrum, but these systems have not been validated externally and compared. Therefore, we examined 36 cases of systemic Epstein-Barr virus-positive T-cell and NK-cell lymphoproliferative diseases of childhood with long-term follow-up, from Southwest China, to systematically summarize the clinicopathologic features and to validate and compare the Ohshima Grading System and the 2017 WHO classification in discrimination ability, predictive accuracy, concordance indices, and explained variation.

Self-efficacy Mediates Perceived Benefits and Barriers of Adherence of Heroin-dependent Patients to Methadone for Addiction Treatment: A Health Belief Model Study.

Objective: Although methadone for addiction treatment (MAT) has been widely used in China, the low adherence rate in MAT clinics poses a great challenge. We aimed to investigate the factors related to the adherence of heroin-dependent patients to MAT based on the Health Belief Model (HBM) in Sichuan, China.

Methods: A cross-sectional structured interview was conducted between August and November 2018.

Morphologic Patterns and the Correlation With MYD88 L265P, CD79B Mutations in Primary Adrenal Diffuse Large B-Cell Lymphoma.

Primary adrenal diffuse large B-cell lymphoma (PA-DLBCL) is a rare subtype of extranodal DLBCL. Because of the rarity of this disease, its morphologic and genetic features are not comprehensively studied. Here, we systematically reviewed the clinicopathologic features of 42 cases of PA-DLBCL from our institution and investigated the frequency of MYD88 L265P and CD79B (exon 5) mutation in 29 eligible cases using Sanger sequencing.

Chronic Active Epstein-Barr Virus Infection of T/NK-Cell Type Mimicking Classic Hodgkin Lymphoma: Clinicopathologic and Genetic Features of 8 Cases Supporting a Variant With "Hodgkin/Reed-Sternberg-like" Cells of NK Phenotype.

Chronic active Epstein-Barr virus (EBV) infection of T-cell and NK-cell type, systemic form (CAEBV-T/NK-S) is characterized by EBV T-cell and/or NK-cell proliferation with no changes suggesting malignancy. Therefore, when Hodgkin/Reed-Sternberg (HRS)-like cells are scattered in CAEBV-T/NK-S, it is more likely to be misdiagnosed as classic Hodgkin lymphoma. We encountered a case wherein the patient showed HRS-like cells with typical NK phenotype.

Extranodal NK/T-cell lymphoma in adolescents: imaging findings of a consecutive 7-year case series.

Objectives: Extranodal NK/T-cell lymphoma is reportedly a rare but emerging type of lymphoma in adolescents. The present study was performed to specify its imaging characteristics.

Methods: Our hospital's picture archiving and communication systems were searched from January 2009 to December 2016.

Volume alteration of hippocampal subfields in first-episode antipsychotic-naïve schizophrenia patients before and after acute antipsychotic treatment.

The nature of hippocampal changes in schizophrenia before first treatment, and whether hippocampal subfields are affected by antipsychotic treatment are important questions for schizophrenia research. Forty-one first-episode antipsychotic-naïve acutely ill schizophrenia inpatients had MRI scans before and six weeks after antipsychotic treatment. Thirty-nine matched healthy controls were also scanned, twenty-two of which were scanned a second time six weeks later.

CD30 expression and survival in extranodal NK/T-cell lymphoma: a systematic review and meta-analysis.

Background: The paradoxical reports about the prognostic value of the CD30 expression in extranodal NK/T-cell lymphoma (ENKTL) have restricted its further applications in clinical practice. To identify the common effects and the variation, we conducted this systematic review and meta-analysis.

Methods: PubMed, MEDLINE, Embase, and Web of Science were searched between January 1975 and 31 January 2017.

Dilemmas in a pregnant woman with myelofibrosis secondary to signet ring adenocarcinoma: a case report.

Background: We describe the first reported case of myelofibrosis as an extremely rare complication of gastric cancer during pregnancy; the clinical diagnosis and treatment of which is highly challenging due to nonspecific symptoms coupled with the conflicting needs of immediate disease control and continuation of pregnancy.

Case Presentation: We report a 36-year-old pregnant woman who presented with cytopenia, fatigue, vomiting, and diarrhea for 20 days on the background of newly diagnosed myelofibrosis secondary to gastric signet ring adenocarcinoma. She accepted palliative care and died several months after the delivery of a healthy newborn.

Unusual clotted haemothorax caused by spontaneous intramural haematoma of the oesophagus: a case report.

Spontaneous intramural haematoma of the oesophagus (SIHO) is a relatively rare event with benign courses. Most of the patients with SIHO may experience spontaneous healing without complications. We report a case of SIHO with clotted haemothorax.

Potential role of exosome-associated microRNA panels and in vivo environment to predict drug resistance for patients with multiple myeloma.

Multiple myeloma (MM) is the second most common hematologic neoplasms and an appropriate in vivo environment for myeloma cells has potential implications for initiation, progression, and metastasis of MM. Exosomes, entities carrying microRNAs (miRNAs) to target locations, participate in the cross-talk between myeloma cells and nonmalignant components of the in vivo environment. This study disclosed the emerging roles of circulating exosome-associated miRNAs in drug resistance (DR) of MM.

Enzyme- and pH-Sensitive Branched Polymer-Doxorubicin Conjugate-Based Nanoscale Drug Delivery System for Cancer Therapy.

Owing to their dendritic architectural features, branched copolymers have been investigated as drug delivery systems. In this paper, an enzyme- and pH-sensitive branched poly[N-(2-hydroxypropyl)methacrylamide] (polyHPMA) copolymer-doxorubicin (DOX) conjugate possessing a molecular weight (MW) of 165 kDa was designed and prepared via a one-pot reaction and drug conjugation. This conjugate's potential as a smart, nanoscale drug delivery system (NDDS) is also investigated.

Stimuli-Responsive Biodegradable Hyperbranched Polymer-Gadolinium Conjugates as Efficient and Biocompatible Nanoscale Magnetic Resonance Imaging Contrast Agents.

The efficacy and biocompatibility of nanoscale magnetic resonance imaging (MRI) contrast agents depend on optimal molecular structures and compositions. Gadolinium [Gd(III)] based dendritic macromolecules with well-defined and tunable nanoscale sizes are excellent candidates as multivalent MRI contrast agents. Here, we propose a novel alternate preparation of biodegradable hyperbranched polymer-gadolinium conjugates via a simple strategy and report potentially efficient and biocompatible nanoscale MRI contrast agents for cancer diagnosis.