The concentration gradient of K across the cell membrane of a neuron determines its resting potential and cell excitability. During neurotransmission, the efflux of K from the cell via various channels will not only decrease the intracellular K content but also elevate the extracellular K concentration. However, it is not clear to what extent this change could be. In this study, we developed a multiple-parallel-connected silicon nanowire field-effect transistor (SiNW-FET) modified with K-specific DNA-aptamers (aptamer/SiNW-FET) for the real-time detection of the K efflux from cultured cortical neurons. The aptamer/SiNW-FET showed an association constant of (2.18 ± 0.44) × 10 M against K and an either less or negligible response to other alkali metal ions. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) stimulation induced an outward current and hyperpolarized the membrane potential in a whole-cell patched neuron under a Na/K-free buffer. When neurons were placed atop the aptamer/SiNW-FET in a Na/K-free buffer, AMPA (13 μM) stimulation elevated the extracellular K concentration to ∼800 nM, which is greatly reduced by 6,7-dinitroquinoxaline-2,3-dione, an AMPA receptor antagonist. The EC of AMPA in elevating the extracellular K concentration was 10.3 μM. By stimulating the neurons with AMPA under a normal physiological buffer, the K concentration in the isolated cytosolic fraction was decreased by 75%. These experiments demonstrate that the aptamer/SiNW-FET is sensitive for detecting cations and the K concentrations inside and outside the neurons could be greatly changed to modulate the neuron excitability.
Background
This systematic review and meta-analysis aimed to investigate the clinical efficacy and safety of systemic corticosteroids in the treatment of patients with severe community-acquired pneumonia (sCAP).
Methods
A comprehensive search was conducted using the Medline, Embase, ClinicalTrials.gov, and Scopus databases for articles published until April 24, 2023. Only randomized controlled trials (RCTs) that assessed the clinical efficacy and safety of adjunctive corticosteroids for treating sCAP were included. The primary outcome was the 30-day all-cause mortality.
Results
A total of severe RCTs involving 1689 patients were included in this study. Overall, the study group had a lower mortality rate at day 30 than the control group (risk ratio [RR], 0.61; 95% CI 0.44 to 0.85; p < 0.01) with low heterogeneity (I2 = 0%, p = 0.42). Compared to the control group, the study group had a lower risk of the requirement of mechanical ventilation (RR 0.57; 95% CI 0.45 to 0.73; p < 0.001), shorter length of intensive care unit (MD − 0.8; 95% CI − 1.4 to − 0.1; p = 0.02), and hospital stay (MD − 1.1; 95% CI − 2.0 to − 0.1; p = 0.04). Finally, no significant difference was observed between the study and the control groups in terms of gastrointestinal tract bleeding (RR 1.03; 95% CI 0.49 to 2.18; p = 0.93), healthcare-associated infection (RR 0.89; 95% CI 0.60 to 1.32; p = 0.56), and acute kidney injury (RR 0.68; 95% CI 0.21 to 2.26; p = 0.53).
Conclusions
In patients with sCAP, adjunctive corticosteroids can provide survival benefits and improve clinical outcomes without increasing adverse events. However, because the pooled evidence remains inconclusive, further studies are required.
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