Impact of Stenosis Degree on Outcomes of Stenting versus Medical Treatment Alone for Symptomatic Intracranial Stenosis: A Pooled Individual Patient Data Analysis.

Background And Purpose: This study explores the impact of stenosis degree on outcomes of stenting compared with medical therapy alone in patients with symptomatic intracranial artery stenosis.

Materials And Methods: Patients with a transient ischemic attack or nondisabling ischemic stroke, attributed to 70 to 99% stenosis of a major intracranial artery, were included. The patient cohort was drawn from the China Angioplasty and Stenting for Symptomatic Intracranial Severe Stenosis (CASSISS) and the Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS).

Validation Status of Electronic Sphygmomanometers in China: A National Survey.

Background: Although the information on the validation status of electronic sphygmomanometer (ES) devices in use in health care institutions and households is much more clinically relevant than that of ES models available on the market, it remains insufficient.

Methods: A national survey was conducted across all administrative regions of mainland China to assess the validation status of ESs. Fifty-eight cities were selected with stratification by municipality, provincial capital, and other cities, and health care institutions and households in each city were chosen by convenience to identify ES devices in use according to the study protocol.

Novel Naphthyridones Targeting Pannexin 1 for Colitis Management.

Pannexin 1 (PANX1) forms cell-surface channels capable of releasing signaling metabolites for diverse patho-physiological processes. While inhibiting dysregulated PANX1 has been proposed as a therapeutic strategy for many pathological conditions, including inflammatory bowel disease (IBD), low efficacy, or poor specificity of classical PANX1 inhibitors introduces uncertainty for their applications in basic and translational research. Here, hit-to-lead optimization is performed and a naphthyridone, compound 12, is identified as a new PANX1 inhibitor with an IC of 0.

SARS-CoV-2 infection of human pluripotent stem cell-derived vascular cells reveals smooth muscle cells as key mediators of vascular pathology during infection.

Although respiratory symptoms are the most prevalent disease manifestation of infection by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), nearly 20% of hospitalized patients are at risk for thromboembolic events. This prothrombotic state is considered a key factor in the increased risk of stroke, which is observed clinically during both acute infection and long after symptoms clear. Here, we develop a model of SARS-CoV-2 infection using human-induced pluripotent stem cell-derived endothelial cells (ECs), pericytes (PCs), and smooth muscle cells (SMCs) to recapitulate the vascular pathology associated with SARS-CoV-2 exposure.

Dual Antiplatelet Treatment up to 72 Hours After Ischemic Stroke Stratified by Risk Profile: A Post Hoc Analysis.

Background: Risk profile of recurrence may influence the effect of antiplatelet therapy. This study aimed to evaluate the efficacy and safety of clopidogrel-aspirin initiated within 72 hours after symptom onset for acute mild stroke or high-risk transient ischemic attack stratified by risk profile.

Methods: This is a secondary post hoc analysis of the INSPIRES (Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis) randomized clinical trial that enrolled patients 35 to 80 years old with acute mild ischemic stroke or high-risk transient ischemic attack between 2018 and 2022.

Probiotics and their metabolite spermidine enhance IFN-γCD4 T cell immunity to inhibit hepatitis B virus.

The therapeutic potential of commensal microbes and their metabolites is promising in the functional cure of chronic hepatitis B virus (HBV) infection, which is defined as hepatitis B surface antigen (HBsAg) loss. Here, using both specific-pathogen-free and germ-free mice, we report that probiotics significantly promote the decline of HBsAg and inhibit HBV replication by enhancing intestinal homeostasis and provoking intrahepatic interferon (IFN)-γCD4 T cell immune response. Depletion of CD4 T cells or blockage of IFN-γ abolishes probiotics-mediated HBV inhibition.

Outcomes After Osteochondral Allograft Transplantation of the Medial Femoral Condyle in Patients With Varus and Nonvarus Alignment.

Background: Fresh osteochondral allograft (OCA) transplantation is an effective technique for the treatment of focal chondral and osteochondral defects in the knee. Coronal-plane malalignment leads to increased contact forces within a compartment and subsequently the cartilage repair site and may lead to higher failure rates. However, the magnitude of the effect of coronal-plane malalignment on graft survivorship and clinical outcomes has not been well characterized.

Duration of Benefit and Risk of Dual Antiplatelet Therapy up to 72 Hours After Mild Ischemic Stroke and Transient Ischemic Attack.

Background And Objectives: Clopidogrel-aspirin initiated within 72 hours of symptom onset is effective in patients with mild ischemic stroke or transient ischemic attack (TIA) in the Intensive Statin and Antiplatelet Therapy for Acute High-risk Intracranial or Extracranial Atherosclerosis (INSPIRES) trial. Uncertainties remain about the duration of the treatment effect. This study aimed to assess duration of benefit and risk of clopidogrel-aspirin in these patients.

Perivascular spaces, plasma GFAP, and speeded executive function in neurodegenerative diseases.

Introduction: We investigated the effect of perivascular spaces (PVS) volume on speeded executive function (sEF), as mediated by white matter hyperintensities (WMH) volume and plasma glial fibrillary acidic protein (GFAP) in neurodegenerative diseases.

Methods: A mediation analysis was performed to assess the relationship between neuroimaging markers and plasma biomarkers on sEF in 333 participants clinically diagnosed with Alzheimer's disease/mild cognitive impairment, frontotemporal dementia, or cerebrovascular disease from the Ontario Neurodegenerative Disease Research Initiative.

Results: PVS was significantly associated with sEF (c = -0.

Improved efficacy and safety of zanubrutinib versus ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (R/R CLL) in China: a subgroup of ALPINE.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has different epidemiology in Chinese vs. Western patients, but there are few studies of CLL/SLL in large populations of Chinese patients. ALPINE is a global phase 3 trial investigating Bruton tyrosine kinase inhibitors zanubrutinib vs.

Uniformly elevated future heat stress in China driven by spatially heterogeneous water vapor changes.

The wet bulb temperature (T) has gained considerable attention as a crucial indicator of heat-related health risks. Here we report south-to-north spatially heterogeneous trends of T in China over 1979-2018. We find that actual water vapor pressure (E) changes play a dominant role in determining the different trend of T in southern and northern China, which is attributed to the faster warming of high-latitude regions of East Asia as a response to climate change.

Effect of Cangrelor on Infarct Size in ST-Segment-Elevation Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (The PITRI Trial).

Background: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarction (MI) size in the preclinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction in patients with ST-segment-elevation MI undergoing primary percutaneous coronary intervention.

Methods: This was a phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trial conducted between November 2017 to November 2021 in 6 cardiac centers in Singapore.

ABCG2-Expressing Clonal Repopulating Endothelial Cells Serve to Form and Maintain Blood Vessels.

Background: Most organs are maintained lifelong by resident stem/progenitor cells. During development and regeneration, lineage-specific stem/progenitor cells can contribute to the growth or maintenance of different organs, whereas fully differentiated mature cells have less regenerative potential. However, it is unclear whether vascular endothelial cells (ECs) are also replenished by stem/progenitor cells with EC-repopulating potential residing in blood vessels.

Suture Anchor Technique for Bridge Enhanced Anterior Cruciate Ligament Restoration.

Anterior cruciate ligament (ACL) injuries are common in the athletic population. ACL repair with bridge enhancement is an emerging technology with promising clinical outcomes in patients with a proximal to midsubstance ACL tears. Currently, there are a variety of fixation methods described for isolated ACL repair, including suspensory and anchor techniques.

A Novel, Controllable, and Efficient Method for Building Highly Hydrophobic Aerogels.

Aerogels prepared using freeze-drying methods have the potential to be insulation materials or absorbents in the fields of industry, architecture, agriculture, etc., for their low heat conductivity, high specific area, low density, degradability, and low cost. However, their native, poor water resistance caused by the hydrophilicity of their polymer matrix limits their practical application.

Dual Antiplatelet Treatment up to 72 Hours after Ischemic Stroke.

Background: Dual antiplatelet treatment has been shown to lower the risk of recurrent stroke as compared with aspirin alone when treatment is initiated early (≤24 hours) after an acute mild stroke. The effect of clopidogrel plus aspirin as compared with aspirin alone administered within 72 hours after the onset of acute cerebral ischemia from atherosclerosis has not been well studied.

Methods: In 222 hospitals in China, we conducted a double-blind, randomized, placebo-controlled, two-by-two factorial trial involving patients with mild ischemic stroke or high-risk transient ischemic attack (TIA) of presumed atherosclerotic cause who had not undergone thrombolysis or thrombectomy.

Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer.

Background: Neoadjuvant or adjuvant immunotherapy can improve outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Perioperative regimens may combine benefits of both to improve long-term outcomes.

Methods: We randomly assigned patients with resectable NSCLC (stage II to IIIB [N2 node stage] according to the eighth edition of the ) to receive platinum-based chemotherapy plus durvalumab or placebo administered intravenously every 3 weeks for 4 cycles before surgery, followed by adjuvant durvalumab or placebo intravenously every 4 weeks for 12 cycles.

SIRT3 Regulates Clearance of Apoptotic Cardiomyocytes by Deacetylating Frataxin.

Background: Efferocytosis is an activity of macrophages that is pivotal for the resolution of inflammation in hypertension. The precise mechanism by which macrophages coordinate efferocytosis and internalize apoptotic cardiomyocytes remains unknown. The aim of this study was to determine whether SIRT3 (sirtuin-3) is required for both apoptotic cardiomyocyte engulfment and anti-inflammatory responses during efferocytosis.

RBFOX2 recognizes N-methyladenosine to suppress transcription and block myeloid leukaemia differentiation.

N-methyladenosine (mA) methylation can be deposited on chromatin-associated RNAs (caRNAs) by the RNA methyltransferase complex (MTC) to regulate chromatin state and transcription. However, the mechanism by which MTC is recruited to distinct genomic loci remains elusive. Here we identify RBFOX2, a well-studied RNA-binding protein, as a chromatin factor that preferentially recognizes mA on caRNAs.

Clinical Relevance of Plaque Distribution for Basilar Artery Stenosis.

Background And Purpose: There is no clear association between plaque distribution and postoperative complications in patients with basilar artery atherosclerotic stenosis. The aim of this study was to determine whether plaque distribution and postoperative complications after endovascular treatment for basilar artery stenosis are related.

Materials And Methods: Our study enrolled patients with severe basilar artery stenosis who were scanned with high-resolution MR imaging and followed by DSA before the intervention.

Novel Calmodulin Variant p.E46K Associated With Severe Catecholaminergic Polymorphic Ventricular Tachycardia Produces Robust Arrhythmogenicity in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

Background: CaM (calmodulin) is a ubiquitously expressed, multifunctional Ca sensor protein that regulates numerous proteins. Recently, CaM missense variants have been identified in patients with malignant inherited arrhythmias, such as long QT syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT). However, the exact mechanism of CaM-related CPVT in human cardiomyocytes remains unclear.