Nasal irrigation with licorice extract (Glycyrrhiza glabra) in treating nasal polyps by reducing fibroblast differentiation and extracellular matrix production in TGF-ß1-stimulated nasal polyp-derived fibroblasts by inhibiting the MAPK/ERK-1/2 pathway - an in vitro and in clinic study.

BACKGROUND: To date, treating nasal polyps (NPs) is still a medical challenge. However, we have developed an innovative therapy using licorice extract (LE: Glycyrrhiza glabra) to treat rhinitis and sinusitis via nasal irrigation and have discovered that it significantly affects treatment of NPs. HYPOTHESIS/PURPOSE: This study investigated the mechanism of LE on NPs. STUDY DESIGN: NPs were collected from three patients using tissue biopsies before and 2 weeks after nasal irrigation with licorice for histopathological analysis. Additionally, NPs from two patients were collected, and nasal polyp-derived fibroblasts (NPDF) were isolated and cultured. METHODS: The TGF-ß1-stimulated NPDF model was used to examine the effect of LE on fibroblast differentiation (biomarker: α-SMA), the consequent production of extracellular matrix (ECM; biomarkers: fibronectin, FBN), and the functional signaling pathway. RESULTS: Immunohistochemistry (IHC) revealed that the number of eosinophils and the expression of α-SMA and interstitial collagen of polyps after licorice treatment significantly decreased. Additionally, RT-PCR, western blotting, and immunofluorescence (IF) showed that α-SMA and FBN expressions were significantly increased in the NPDF, which was stimulated by TGF-ß1, and LE dose-dependently could effectively reduce this effect. Furthermore, western blotting showed that LE could attenuate α-SMA and FBN expressions by preventing the signaling pathway of MAPK/ERK-1/2, which IHC and IF further confirmed. In addition, LE effectively suppressed the cell migration of NPDF, which is related to polyp expansion. CONCLUSION: LE is clinically used to treat sinusitis with NPs through nasal irrigation, which significantly reduces the size of NPs. This effect could attenuate fibroblast differentiation, ECM production and cell migration, and one of the functional mechanisms may be through inhibition of the MAPK/ERK-1/2 signaling pathway. TRIAL REGISTRATION: ISRCTN (No. 51425529) registered on 17/04/2020 (retrospectively registered) - http://www.isrctn.com/ISRCTN51425529.

Nasal irrigation with Glycyrrhiza glabra extract for treatment of allergic rhinitis - A study of in vitro, in vivo and clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Glycyrrhiza glabra, a family of licorice and a traditional Chinese medicine with sweet taste and favorable smell, has anti-inflammatory, anti-allergic and immunomodulatory functions. AIM OF THE STUDY: We developed a licorice extract (LE) by using glycyrrhiza glabra and administered it through nasal irrigation to treat allergic rhinitis (AR). MATERIALS AND METHODS: LE was prepared into extract powder, and the anti-inflammatory effect of the LE was evaluated by calcium ionophore-induced activated mast cell model (in vitro). Then, local passive anaphylaxis assays were applied to investigate the anti-IgE-mediated allergic reaction of the LE in mice (in vivo). A developed LE was administered through nasal irrigation to treat AR in clinic settings. A total of 60 participants diagnosed with AR were included in this clinical trial; they were randomly assigned to three interventions: licorice nasal irrigation (LNI), corticosteroid nasal irrigation (CNI), and saline nasal irrigation (SNI). They performed nasal irrigation once a day for 1 month. Both subjective questionnaires (22-item Sino-Nasal Outcome Test [SNOT-22] and visual analog scale [VAS]) and objective examinations (acoustic rhinometry and nasal endoscopy) were used for effectiveness assessments. RESULTS: All three interventions could improve SNOT-22 scores, but the effects of LNI and CNI were more significant. According to VAS scores for nasal blockage, rhinorrhea, sneezing, nasal pruritus, postnasal discharge, and olfactory disturbance, the effect of LNI was superior to those of CNI and SNI. The results of rhinometry revealed that LNI significantly improved nasal resistance. Endoscopic analysis showed that both LNI and CNI, but not SNI, could significantly improve turbinate hypertrophy. Moreover, the best procedural comfort was found for LNI, which had no side effects or complications during the trial. CONCLUSIONS: LNI is a natural, safe, and innovative therapy that can effectively treat AR. Its effect is superior to those of CNI and SNI, and it has greatly improved procedural comfort.

Novel assessment of temporal variation in fractionated electrograms using histogram analysis of local fractionation interval in patients with persistent atrial fibrillation.

BACKGROUND: The characteristics of atrial electrograms associated with atrial fibrillation (AF) termination are controversial. We investigated the electrogram characteristics that indicate procedural AF termination during continuous complex fractionated electrogram ablation. METHODS AND RESULTS: Fifty-two consecutive patients with persistent AF (47 men; aged 54 ± 9 years), who underwent electrogram-based catheter ablation in the left atrium and coronary sinus after pulmonary vein isolation, were enrolled. The intracardiac bipolar atrial electrogram recordings were characterized by (1) fractionation interval (FI) analysis (>6 seconds), (2) kurtosis (shape of the FI histogram), and (3) skewness (asymmetry of the FI histogram). Sites showing complex, fractionated electrograms (mean FI ≤ 60 ms) were targeted, and AF was terminated in 20 patients (38%) after the pulmonary vein isolation. The conventional complex fractionated electrogram sites (mean ≤ 120 ms) in patients with AF termination exhibited higher median kurtosis (2.69 [interquartile range, 2.03-3.46] versus 2.35 [interquartile range, 1.79-2.48]; P=0.024) and higher complex fractionated electrogram-mean interval (102.7 ± 19.8 versus 87.7 ± 15.0; P=0.008) than patients without AF termination. Furthermore, AF termination sites had higher median kurtosis than targeted sites without AF termination (5.13 [interquartile range, 3.51-6.47] versus 4.18 [interquartile range, 2.91-5.34]; P<0.01) in patients with procedural termination. In addition, patients with AF termination had a higher sinus rhythm maintenance rate after a single procedure than patients without AF termination (log-rank test, P=0.007). CONCLUSIONS: A kurtosis analysis using the FI histogram may be a useful tool in identifying the critical substrate for persistent AF and potential responders to catheter ablation.

Graphics processing unit-based high-frame-rate color Doppler ultrasound processing.

Color Doppler ultrasound is a routinely used diagnostic tool for assessing blood flow information in real time. The required signal processing is computationally intensive, involving autocorrelation, linear filtering, median filtering, and thresholding. Because of the large amount of data and high computational requirement, color Doppler signal processing has been mainly implemented on custom-designed hardware, with software-based implementation--particularly on a general-purpose CPU--not being successful. In this paper, we describe the use of a graphics processing unit for implementing signal-processing algorithms for color Doppler ultrasound that achieves a frame rate of 160 fps for frames comprising 500 scan lines x 128 range samples, with each scan line being obtained from an ensemble size of 8 with an 8-tap FIR clutter filter.