Long-Term Outcomes of Indirect Bypass for 629 Children With Moyamoya Disease: Longitudinal and Cross-Sectional Analysis.

Background and Purpose- In pediatric moyamoya disease, there are few reports on the efficacy of surgical intervention for stroke prevention. We evaluated the long-term outcomes of indirect bypass surgery on a relatively large number of children with moyamoya disease in a single center. Methods- From August 1988 to December 2012, 772 children underwent indirect bypass surgery.

Endothelial Targets in Stroke: Translating Animal Models to Human.

Cerebral ischemia (stroke) induces injury to the cerebral endothelium that may contribute to parenchymal injury and worsen outcome. This review focuses on current preclinical studies examining how to prevent ischemia-induced endothelial dysfunction. It particularly focuses on targets at the endothelium itself.

Evidence of long-lasting anti-CD19 activity of engrafted CD19 chimeric antigen receptor-modified T cells in a phase I study targeting pediatrics with acute lymphoblastic leukemia.

Ninety percent of relapse/refractory B-cell acute lymphatic leukemia (R/R B-ALL) patients can achieve complete remission (CR) after CD19-targeting chimeric antigen receptor T (CAR-T) cell therapy. However, around 50% of them relapse in 1 year. Persistent CAR-T cell engraftment is considered as the key to remain durable remission.

Roles of the hypoximir microRNA-424/322 in acute hypoxia and hypoxia-induced pulmonary vascular leakage.

Acute mountain sickness (AMS) occurs in up to 25% of unacclimatized persons who ascend to 3000 m and can result in high-altitude pulmonary edema (HAPE). MicroRNAs (miRs) can regulate gene expression at the post-transcriptional level. Hypoxia selectively disrupts endothelial tight junction complexes through a hypoxia-inducible factor-1α (HIF-1α)-dependent mechanism.

Baseline Plasma Zinc and Risk of First Stroke in Hypertensive Patients: A Nested Case-Control Study.

Background and Purpose- We aimed to examine the relation of baseline plasma zinc with the risk of first stroke and investigate any possible effect modifiers in hypertensive patients. Methods- The study population was drawn from the CSPPT (China Stroke Primary Prevention Trial), using a nested case-control design, including 599 first stroke cases and 599 matched controls. Results- Compared with participants with baseline plasma zinc <106.

Variant Interpretation for Cancer (VIC): a computational tool for assessing clinical impacts of somatic variants.

Background: Clinical laboratories implement a variety of measures to classify somatic sequence variants and identify clinically significant variants to facilitate the implementation of precision medicine. To standardize the interpretation process, the Association for Molecular Pathology (AMP), American Society of Clinical Oncology (ASCO), and College of American Pathologists (CAP) published guidelines for the interpretation and reporting of sequence variants in cancer in 2017. These guidelines classify somatic variants using a four-tiered system with ten criteria.

Regulation of YAP by Mammalian Target of Rapamycin Complex 1 in Endothelial Cells Controls Blood Pressure Through COX-2/mPGES-1/PGE Cascade.

Endothelial cells regulate vascular tone by producing both relaxing and contracting factors to control the local blood flow. Hypertension is a common side effect of mTORC1 (mammalian target of rapamycin complex 1) inhibitors. However, the role of endothelial mTORC1 in hypertension remains elusive.

CRISPR Editing of Mutant IDH1 R132H Induces a CpG Methylation-Low State in Patient-Derived Glioma Models of G-CIMP.

Mutations in isocitrate dehydrogenases 1 and 2 (IDH) occur in the majority of World Health Organization grade II and III gliomas. IDH1/2 active site mutations confer a neomorphic enzyme activity producing the oncometabolite D-2-hydroxyglutarate (D-2HG), which generates the glioma CpG island methylation phenotype (G-CIMP). While IDH1/2 mutations and G-CIMP are commonly retained during tumor recurrence, recent work has uncovered losses of the IDH1 mutation in a subset of secondary glioblastomas.

Down-regulation of ATF1 leads to early neuroectoderm differentiation of human embryonic stem cells by increasing the expression level of SOX2.

We reveal by high-throughput screening that activating transcription factor 1 (ATF1) is a novel pluripotent regulator in human embryonic stem cells (hESCs). The knockdown of ATF1 expression significantly up-regulated neuroectoderm (NE) genes but not mesoderm, endoderm, and trophectoderm genes. Of note, down-regulation or knockout of ATF1 with short hairpin RNA (shRNA), small interfering RNA (siRNA), or clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) was sufficient to up-regulate sex-determining region Y-box (SOX)2 and paired box 6 (PAX6) expression under the undifferentiated or differentiated conditions, whereas overexpression of ATF1 suppressed NE differentiation.

Author Correction: Loss of function of NCOR1 and NCOR2 impairs memory through a novel GABAergic hypothalamus-CA3 projection.

In the version of this article initially published, the Acknowledgements erroneously included a grant number that did not directly support the work in the article. The last sentence of the Acknowledgments should have read, "The authors' laboratories were supported by National Natural Science Foundation of China grants 31671222 and 31571556 (G.D.

Complement Inhibition Attenuates Early Erythrolysis in the Hematoma and Brain Injury in Aged Rats.

Background and Purpose- Early erythrolysis in the hematoma contributes to brain injury after intracerebral hemorrhage (ICH). This study investigated the effects of N-acetylheparin, a complement inhibitor, and aurin tricarboxylic acid, a membrane attack complex inhibitor, on early erythrolysis, brain iron deposition, and brain injury in aged rats. Methods- There were 3 parts in the study.

Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma.

Background: Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials.

Methods: In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone.

Enhancement of Hematoma Clearance With CD47 Blocking Antibody in Experimental Intracerebral Hemorrhage.

Background and Purpose- Our previous studies found that erythrocyte CD47 has a role in regulating hematoma resolution following experimental intracerebral hemorrhage (ICH). The current study examined whether or not a CD47 blocking antibody enhances hematoma clearance in a mouse ICH. Methods- ICH was induced by intracaudate injection of autologous blood in adult C57BL/6 mice.

Serum Phosphate and the Risk of New-Onset Hyperuricemia in Hypertensive Patients.

The relationship of serum phosphate and new-onset hyperuricemia remains uncertain. We aimed to evaluate the relationship of serum phosphate with the risk of new-onset hyperuricemia, and to examine any possible effect modifiers in hypertensive patients. This is a post hoc analysis of the Uric Acid substudy of the CSPPT (China Stroke Primary Prevention Trial).

Elemene injection as adjunctive treatment to platinum-based chemotherapy in patients with stage III/IV non-small cell lung cancer: A meta-analysis following the PRISMA guidelines.

Background: Elemene injection is an anticancer Chinese patent medicine that is widely used for the treatment of advanced lung cancer. Its active ingredients are β-, γ- and δ-elemene, which are extracted from Curcumaaromatica Salisb. (Curcumawenyujin Y.

Effect of Anti-CD4 Antibody UB-421 on HIV-1 Rebound after Treatment Interruption.

Background: Administration of a single broadly neutralizing human immunodeficiency virus (HIV)-specific antibody to HIV-infected persons leads to the development of antibody-resistant virus in the absence of antiretroviral therapy (ART). It is possible that monotherapy with UB-421, an antibody that blocks the virus-binding site on human CD4+ T cells, could induce sustained virologic suppression without induction of resistance in HIV-infected persons after analytic treatment interruption.

Methods: We conducted a nonrandomized, open-label, phase 2 clinical study evaluating the safety, pharmacokinetics, and antiviral activity of UB-421 monotherapy in HIV-infected persons undergoing analytic treatment interruption.

Adventitial Cell Atlas of wt (Wild Type) and ApoE (Apolipoprotein E)-Deficient Mice Defined by Single-Cell RNA Sequencing.

Objective- Vascular adventitia encompasses progenitors and is getting recognized as the major site of inflammation in early stage of atherosclerosis. However, the cellular atlas of the heterogeneous adventitial cells, the intercellular communication, the cellular response of adventitia to hyperlipidemia, and its contribution to atherosclerosis have been elusive. Approach and Results- Single-cell RNA sequencing was applied to wt (wild type) and ApoE (apolipoprotein E)-deficient aortic adventitia from 12-week-old C57BL/6J mice fed on normal laboratory diet with early stage of atherosclerosis.

SNX17 (Sorting Nexin 17) Mediates Atrial Fibrillation Onset Through Endocytic Trafficking of the Kv1.5 (Potassium Voltage-Gated Channel Subfamily A Member 5) Channel.

Background: Kv1.5 (Potassium voltage-gated channel subfamily A member 5) has been regarded as a promising target of interventions for atrial fibrillation (AF). SNX17 (sorting nexin 17), a member of the SNXs (sorting nexin family), regulates the intracellular trafficking of membrane proteins through its FERM (four-point-one, ezrin, radixin, moesin) domain.

Atheroprotective Flow Upregulates ITPR3 (Inositol 1,4,5-Trisphosphate Receptor 3) in Vascular Endothelium via KLF4 (Krüppel-Like Factor 4)-Mediated Histone Modifications.

Objective- The topographical distribution of atherosclerosis in vasculature underscores the importance of shear stress in regulating endothelium. With a systems approach integrating sequencing data, the current study aims to explore the link between shear stress-regulated master transcription factor and its regulation of endothelial cell (EC) function via epigenetic modifications. Approach and Results- H3K27ac (acetylation of histone 3 lysine 27)-ChIP-seq (chromatin immunoprecipitation followed by high throughput sequencing), ATAC-seq (an assay for transposase-accessible chromatin-sequencing), and RNA-seq (RNA-sequencing) were performed to investigate the genome-wide epigenetic regulations in ECs in response to atheroprotective pulsatile shear stress (PS).

Longterm Exercise-Derived Exosomal miR-342-5p: A Novel Exerkine for Cardioprotection.

Rationale: Exercise training, in addition to reducing cardiovascular risk factors, confers direct protection against myocardial ischemia/reperfusion injury and has been associated with improved heart attack survival in humans. However, the underlying mechanisms of exercise-afforded cardioprotection are still unclear.

Objective: To investigate the role of exercise-derived circulating exosomes in cardioprotection and the molecular mechanisms involved.

Raw and vinegar processed Curcuma wenyujin regulates hepatic fibrosis via bloking TGF-β/Smad signaling pathways and up-regulation of MMP-2/TIMP-1 ratio.

Ethnopharmacological Relevance: Curcuma wenyujin Y.H. (CW), a variety of Curumae Rhizoma, which documented in China Pharmacopeia, has long been used as plant medicine for its traditional effect on promoting Qi, activating blood stagnation and expelling blood stasis.

Ambient Coarse Particulate Matter and Hospital Admissions for Ischemic Stroke.

Background and Purpose- Evidence on the effects of coarse particulate matter (PM) on ischemic stroke is limited and inconsistent. We evaluated the acute effects of PM exposure on hospital admissions for ischemic stroke in China. Methods- We conducted a national time-series analysis of associations between daily PM concentrations and daily hospital admissions for ischemic stroke in China between January 2014 and December 2016.

Long Noncoding RNA CPR (Cardiomyocyte Proliferation Regulator) Regulates Cardiomyocyte Proliferation and Cardiac Repair.

Background: The adult mammalian cardiomyocytes lose their proliferative capacity, which is responsible for cardiac dysfunction and heart failure following injury. The molecular mechanisms underlying the attenuation of adult cardiomyocyte proliferation remain largely unknown. Because long noncoding RNAs (lncRNAs) have a critical role in the development of cardiovascular problems, we investigated whether lncRNAs have any role in the regulation of cardiomyocyte proliferation and cardiac repair.

Endothelial TFEB (Transcription Factor EB) Restrains IKK (IκB Kinase)-p65 Pathway to Attenuate Vascular Inflammation in Diabetic db/db Mice.

Objective- TFEB (transcription factor EB) was recently reported to be induced by atheroprotective laminar flow and play an anti-atherosclerotic role by inhibiting inflammation in endothelial cells (ECs). This study aims to investigate whether TFEB regulates endothelial inflammation in diabetic db/db mice and the molecular mechanisms involved. Approach and Results- Endothelial denudation shows that TFEB is mainly expressed in ECs in mouse aortas.