LIVE, ATTENUATED VACCINES AND METHODS OF MAKING AND USING

A live, attenuated HIV vaccine is provided, and methods of making a atenuated HIV vaccine are provided

Treatment Effects of the Second-Generation Tyrosine Kinase Inhibitor Dasatinib on Autoimmune Arthritis

Rheumatoid arthritis (RA) is a multifactorial autoimmune disease that primarily manifests as persistent synovitis and progressive joint destruction. Imatinib exhibited a therapeutic effect in murine collagen-induced arthritis (CIA) via selective inhibition tyrosine kinases. The second-generation tyrosine kinase inhibitor dasatinib exhibits more durable hematological and cytogenetic effects and more potency compared to imatinib. However, the effect of dasatinib on CIA is poorly understood. The present study investigated the treatment effect of dasatinib on autoimmune arthritis. We demonstrated that dasatinib alleviated arthritis symptoms and histopathological destruction in CIA mice. Dasatinib treatment inhibited the production of proinflammatory cytokines including IL-1β, TNF-α, and IL-6, and promoted the production of the anti-inflammatory cytokine IL-10. Dasatinib treatment also suppressed the expression of anti-mouse CII antibodies including total IgG, IgG1, IgG2, and IgG2b, in CIA mice. We further demonstrated that dasatinib inhibited the migration and proliferation of fibroblast-like synoviocytes (FLS) from RA patients and promoted FLS apoptosis. The mRNA expression of MMP13, VEGF, FGF, and DKK1 was down-regulated in FLS treated with dasatinib. Our findings suggest that dasatinib exhibited treatment effects on CIA mice and that FLS are an important target cell of dasatinib treatment in autoimmune arthritis

A Chinese expert consensus on thoracic endovascular aortic repair of type B aortic dissection with a single-branched stent graft for revascularization of the left subclavian artery

Thoracic endovascular repair (TEVAR) is currently the recommended and most widely used treatment for type B aortic dissection. A major challenge is revascularization of the left subclavian artery in order to extend the landing zone to zone 2 (Ishimaru classification). Various strategies have been used for revascularization, including branched stent graft, fenestrated stent graft, the chimney technique, the parallel technique, and bypass surgery. Single-branched stent graft is one of the most promising strategies, and several products have recently been reported as potential candidates for use with this approach. The Castor single-branched stent graft is the only off-the-shelf product available; this product has been developed through collaboration between Chinese corporations and clinicians. In this Perspective article, clinical experience and data obtained from TEVAR with the Castor single-branched stent graft are summarized by experienced Chinese experts

Outcomes of thoracic endovascular aortic repair with fenestrated surgeon-modified stent-graft for type B aortic dissections involving the aortic arch

ObjectivesThis retrospective analysis aimed to evaluate the early and midterm outcomes of thoracic endovascular aortic repair (TEVAR) with fenestrated surgeon-modified stent-graft (f-SMSG) for type B aortic dissections (TBAD) involving the aortic arch.MethodsFrom March 2016 to April 2021, 47 consecutive patients were treated using TEVAR with f-SMSG. All patients were diagnosed with TBAD involving the aortic arch.ResultsIn total, 47 patients with TBAD involving the aortic arch were treated with f-SMSGs. There were 21 zone 1 and 26 zone 2 TEVAR, and 65 arteries were revascularized successfully with fenestrations. Technical success was achieved in 46 patients (97.88%). The 30-day estimated survival (± SE) and reintervention was 93.6 ± 1.0% (95% Confidence Interval [CI], 92.6–94.6%) and 91.5 ± 1.2% (95% CI, 90.3–92.7%), respectively. During a median follow-up of 51 months (range, 16–71 months), 1 patient died of rupture of aortic dissection (AD) and 3 patients died of non-aortic-related reasons. Reintervention was performed for four patients, including two patients of type IA entry flow and two patients of type IB entry flow. No occlusion of the supra-aortic trunk was observed. The estimated survival and reintervention (± SE) at 4 years was 88.7 ± 1.4% (95% CI, 87.3–90.1%) and 84.8 ± 1.5% (95% CI, 83.3–86.3%), respectively.ConclusionThoracic endovascular aortic repair with f-SMSG is an alternative treatment option for TBAD involving the aortic arch in high-volume centers

Influenza C and D Viruses Demonstrated a Differential Respiratory Tissue Tropism in a Comparative Pathogenesis Study in Guinea Pigs

Influenza C virus (ICV) is increasingly associated with community-acquired pneumonia (CAP) in children and its disease severity is worse than the influenza B virus, but similar to influenza A virus associated CAP. Despite the ubiquitous infection landscape of ICV in humans, little is known about its replication and pathobiology in animals. The goal of this study was to understand the replication kinetics, tissue tropism, and pathogenesis of human ICV (huICV) in comparison to the swine influenza D virus (swIDV) in guinea pigs. Intranasal inoculation of both viruses did not cause clinical signs, however, the infected animals shed virus in nasal washes. The huICV replicated in the nasal turbinates, soft palate, and trachea but not in the lungs while swIDV replicated in all four tissues. A comparative analysis of tropism and pathogenesis of these two related seven-segmented influenza viruses revealed that swIDV-infected animals exhibited broad tissue tropism with an increased rate of shedding on 3, 5, and 7 dpi and high viral loads in the lungs compared to huICV. Seroconversion occurred late in the huICV group at 14 dpi, while swIDV-infected animals seroconverted at 7 dpi. Guinea pigs infected with huICV exhibited mild to moderate inflammatory changes in the epithelium of the soft palate and trachea, along with mucosal damage and multifocal alveolitis in the lungs. In summary, the replication kinetics and pathobiological characteristics of ICV in guinea pigs agree with the clinical manifestation of ICV infection in humans, and hence guinea pigs could be used to study these distantly related influenza viruses

LIVE, ATTENUATED VACCINES AND METHODS OF MAKING AND USING

A live, attenuated HIV vaccine is provided, and methods of making a atenuated HIV vaccine are provided

Street Centralities and Land Use Intensities Based on Points of Interest (POI) in Shenzhen, China

Urban land use and transportation are closely associated. Previous studies have investigated the spatial interrelationship between street centralities and land use intensities using land cover data, thus neglecting the social functions of urban land. Taking the city of Shenzhen, China, as a case study, we used reclassified points of interest (POI) data to represent commercial, public service, and residential land, and then investigated the varying interrelationships between the street centralities and different types of urban land use intensities. We calculated three global centralities (“closeness„, “betweenness„, and “straightness„) as well as local centralities (1-km, 2-km, 3-km, and 5-km searching radiuses), which were transformed into raster frameworks using kernel density estimation (KDE) for correlation analysis. Global closeness and straightness are high in the urban core area, and roads with high global betweenness outline the skeleton of the street network. The spatial patterns of the local centralities are distinguished from the global centralities, reflecting local location advantages. High intensities of commercial and public service land are concentrated in the urban core, while residential land is relatively scattered. The bivariate correlation analysis implies that commercial and public service land are more dependent on centralities than residential land. Closeness and straightness have stronger abilities in measuring the location advantages than betweenness. The centralities and intensities are more positively correlated on a larger scale (census block). These findings of the spatial patterns and interrelationships of the centralities and intensities have major implications for urban land use and transportation planning