Asymptomatic carotid stenosis is associated with cognitive impairment independent of known vascular risk factors for vascular cognitive impairment. Approximately 49.4% of these patients demonstrate impairment in at least two neuropsychological domains. The deficit is driven primarily by reduced motor/processing speed and learning/memory and is mild to moderate in severity. The mechanism for impairment is likely to be hemodynamic as evidenced by reduced cerebrovascular reserve and the likely result of hypoperfusion from a pressure drop across the stenosis in the presence of inadequate collateralization.
Azvudine (FNC) is a nucleoside analog that inhibits HIV-1 RNA-dependent RNA polymerase (RdRp). Recently, we discovered FNC an agent against SARS-CoV-2, and have taken it into Phase III trial for COVID-19 patients. FNC monophosphate analog inhibited SARS-CoV-2 and HCoV-OC43 coronavirus with an EC50 between 1.2 and 4.3 μM, depending on viruses or cells, and selective index (SI) in 15–83 range. Oral administration of FNC in rats revealed a substantial thymus-homing feature, with FNC triphosphate (the active form) concentrated in the thymus and peripheral blood mononuclear cells (PBMC). Treating SARS-CoV-2 infected rhesus macaques with FNC (0.07 mg/kg, qd, orally) reduced viral load, recuperated the thymus, improved lymphocyte profiles, alleviated inflammation and organ damage, and lessened ground-glass opacities in chest X-ray. Single-cell sequencing suggested the promotion of thymus function by FNC. A randomized, single-arm clinical trial of FNC on compassionate use (n = 31) showed that oral FNC (5 mg, qd) cured all COVID-19 patients, with 100% viral ribonucleic acid negative conversion in 3.29 ± 2.22 days (range: 1–9 days) and 100% hospital discharge rate in 9.00 ± 4.93 days (range: 2–25 days). The side-effect of FNC is minor and transient dizziness and nausea in 16.12% (5/31) patients. Thus, FNC might cure COVID-19 through its anti-SARS-CoV-2 activity concentrated in the thymus, followed by promoted immunity.
Airway smooth muscle cell (ASMC) was known to involve in the pathophysiology of asthma. Schisandrin B was reported to have anti-asthmatic effects in a murine asthma model. However, the molecular mechanism involving in the effect of Schisandrin B on ASMCs remains poorly understood. Sprague-Dawley rats were divided into three groups: rats as the control (Group 1), sensitized rats (Group 2), sensitized rats and intragastric-administrated Schisandrin B (Group 3). The expression of miR-135a and TRPC1 was detected in the rats from three groups. Platelet-derived growth factor (PDGF)-BB was used to induce the proliferation of isolated ASMCs, and the expression of miR-135a and TRPC1 was detected in PDGF-BB-treated ASMCs. Cell viability was examined in ASMCs transfected with miR-135a inhibitor or si-TRPC1. The expression of TRPC1 was examined in A10 cells pretreated with miR-135a inhibitor or miR-135a mimic. In this study, we found that Schisandrin B attenuated the inspiratory and expiratory resistances in sensitized rats. Schisandrin B upregulated the mRNA level of miR-135a and decreased the expression of TRPC1 in sensitized rats. In addition, Schisandrin B reversed the expression of miR-135a and TRPC1 in PDGF-BB-induced ASMCs. Si-TRPC1 abrogated the increasing proliferation of ASMCs induced by miR-135a inhibitor. We also found that miR-135a regulated the expression of TRPC1 in the A10 cells. These results demonstrate that Schisandrin B inhibits the proliferation of ASMCs via miR-135a suppressing the expression of TRPC1.
The authors have developed a semiautomatic segmentation algorithm for measuring the VWV of the carotid artery using 3D US images with reduced operator interaction and computational time and higher reproducibility using a commercially available 3D US transducer. Their method is a step forward toward routine longitudinal monitoring of 3D plaque progression.
Background and Purpose-Intra-arterial (IA) rescue procedures are increasingly used to treat acute ischemic stroke. We implemented continuous transcranial Doppler (TCD) monitoring during these procedures to detect any potentially harmful flow changes. Here, we report diagnostic criteria and yield of TCD monitoring. Methods-We studied consecutive acute stroke patients who underwent IA reperfusion procedures. TCD flow signatures during these procedures were analyzed and any abnormal findings were documented. Results-Patients were included only if there was successful insonation through the skull; of 56 eligible patients, 51 were included. IA procedures included IA tissue plasminogen activator, use of the Merci retriever, the Penumbra system, balloon angioplasty, and stenting. On TCD monitoring, contrast injections produced high-intensity signals and increased the mean flow velocity (MFV). Deployment of the Merci device appeared as high-intensity, short-duration signals with a transient MFV decrease of 11.5%. The Penumbra system produced lower-intensity signals with a greater transient decrease in MFV during aspiration. IA tissue plasminogen activator significantly increased MFV by 7.5% over Merci and Penumbra flow velocity changes. Power motion Doppler-TCD detected reocclusion in 13 patients, artery-to-artery embolization in 2 patients, air embolism in 2 patients, and hyperperfusion in 6 patients. Overall, the yield of TCD monitoring was positive in 23 (49%) patients who received IA reperfusion procedures. Conclusions-Our velocity, intensity, and flow signatures criteria for TCD monitoring of IA reperfusion procedures detect reocclusion, hyperperfusion, or thromboembolism and air embolism in nearly half of all procedures. This hemodynamic information can be particularly helpful when neurological assessment is limited or delayed. (Stroke. 2010;41:695-699.)
Background and Purpose-Early deterioration can occur after acute stroke for a variety of reasons. We describe a hemodynamic steal and associated neurological deterioration, the reversed Robin Hood syndrome (RRHS
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