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Glioblastoma (GBM) is an incurable and highly heterogeneous brain tumor, originating from human neural stem/progenitor cells (hNSCs/hNPCs) years ahead of diagnosis. Despite extensive efforts to characterize hNSCs and end-stage GBM at bulk and single-cell levels, the de novo gliomagenic path from hNSCs is largely unknown due to technical difficulties in early-stage sampling and preclinical modeling. Here, we established two highly penetrant hNSC-derived malignant glioma models, which resemble the histopathology and transcriptional heterogeneity of human GBM. Integrating time-series analyses of whole-exome sequencing, bulk and single-cell RNA-seq, we reconstructed gliomagenic trajectories, and identified a persistent NSC-like population at all stages of tumorigenesis. Through trajectory analyses and lineage tracing, we showed that tumor progression is primarily driven by multi-step transcriptional reprogramming and fate-switches in the NSC-like cells, which sequentially generate malignant heterogeneity and induce tumor phenotype transitions. We further uncovered stage-specific oncogenic cascades, and among the candidate genes we functionally validated C1QL1 as a new glioma-promoting factor. Importantly, the neurogenic-to-gliogenic switch in NSC-like cells marks an early stage characterized by a burst of oncogenic alterations, during which transient AP-1 inhibition is sufficient to inhibit gliomagenesis. Together, our results reveal previously undercharacterized molecular dynamics and fate choices driving de novo gliomagenesis from hNSCs, and provide a blueprint for potential early-stage treatment/diagnosis for GBM.BACKGROUND Pfeifer-Weber-Christian disease (PWCD), also referred to as idiopathic nodular panniculitis, is a rare idiopathic disease characterized by lobular panniculitis of adipose tissue with systemic symptoms and multiple organ involvement and is usually treated with corticosteroids and cyclosporine A. We report a case of PWCD that was unresponsive to standard treatment but responded to intravenous immune globulin (IVIG) therapy. CASE REPORT A 35-year-old Korean woman presented with fever, malaise, myalgia, and painful nodules in the left breast. Histology of the breast nodules showed lobular panniculitis consistent with PWCD. She did not respond to corticosteroid and cyclosporine A. She was effectively treated with intravenous immune globulin (IVIG). IVIG therapy began with 60 g (1 g/kg) 4 times per week, 2 times every other week. Subsequently, the IVIG dose was reduced for maintenance therapy to 25 g (400 mg/kg) twice every other week and monthly. The patient showed immediate and dramatic improvement. General signs and symptoms, such as fever, malaise, and myalgia, were absent, and the masses had nearly subsided, with several very small hard nodules remaining for 3 months until the time of this report. CONCLUSIONS IVIG was an effective immunomodulatory therapeutic for PWCD in this case. This report shows that PWCD is a rare condition that is difficult to diagnose, but the histopathology of nodular panniculitis supports the diagnosis. In cases that do not respond to standard immunosuppressive therapy, including corticosteroids and cyclosporine A, IVIG therapy may lead to a favorable response with rapid symptomatic relief.BACKGROUND This study aims to explore the effect of Sinomenine (SIN) on pregnancy outcomes of recurrent spontaneous abortion (RSA) in a mouse model. MATERIAL AND METHODS Thirty female CBA/J mice were allocated into 3 groups randomly, then mated with BALB/c mice (CBA/J×BALB/c) as normal-pregnancy group (n=10), or mated with DBA/2 mice (CBA/J×DBA/2) as RSA model (n=10), or CBA/J×DBA/2 mice treated with SIN as RSA+SIN group (n=10). The number of surviving and reabsorbed embryos in each group were counted on day 13.5 of gestation. The mouse serum was collected to determine the levels of interferon-γ (IFN)-γ and IL-4 by ELISA. Immunohistochemistry, qRT-PCR and immunoblotting were used to determine the location, mRNA and protein expressions of IFN-γ, IL-4, T-bet and GATA3 in the decidual and placental tissue. RESULTS In the RSA group, the amount of reabsorbed embryo was significantly higher than that in the normal-pregnancy group. However, SIN treatment showed a rescue effect on spontaneous abortion in RSA mice. IFN-γ, IL-4, T-bet, and GATA3 were all expressed in placental tissues and mainly located in the cytoplasm. The RSA group demonstrated higher expression levels of IFN-γ and T-bet than in the RSA+SIN and normal-pregnancy groups. Although RSA and RSA+SIN groups showed lower expression levels of IL-4 and GATA3 than in the normal-pregnancy group, there was no significant difference between RSA and RSA+SIN groups regarding IL-4 and GATA expression levels. CONCLUSIONS SIN treatment demonstrates a therapeutic effect on spontaneous abortion in RSA mice, possibly through regulating the balance of Th1/Th2 in maternal circulation and decidual tissues.
Bioresorbable vascular scaffolds (BVSs) have been a disappointment in the evolution of drug-eluting stents used in percutaneous coronary intervention because an excessive number of thrombotic complications have been reported. The aim of this study was to evaluate long-term clinical outcomes of the Absorb BVS in patients treated using a predilation, proper sizing, and post-dilation implantation technique.

The records of 110 patients who had a total of 150 Absorb BVSs implanted were retrospectively analyzed. The rate of major adverse cardiovascular events (MACEs), defined as the composite of cardiac death, target vessel myocardial infarction (MI), and target-lesion revascularization were studied using quantitative coronary angiography.

Of the study population, 80% were male and the mean age was 60±11.3 years. The most common diagnosis was stable angina (84%). The median length of follow-up was 53 months (range 46-59 months). The rate of predilation and postdilation was 100%, and 95%, respectively. The 4-year rate of MACEs was 20% cardiac death in 3 patients (2.7%), target vessel MI in 9 (8.2%), and target lesion revascularization in 20 (18.2%). selleck chemical Definite device thrombosis occurred in 6 of 110 patients (5.5%). One case of very late scaffold thrombosis was observed at 47 months. A small BVS diameter (2.5 mm) was found to be the most powerful independent predictor of a MACE (p=0.05).

The Absorb BVS was associated with an increased risk of adverse events, including late and very late device thrombosis, despite the use of a good implementation protocol.
The Absorb BVS was associated with an increased risk of adverse events, including late and very late device thrombosis, despite the use of a good implementation protocol.
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