Application of color Doppler ultrasound to evaluate and analyze the risk factors of residual stenosis after vertebral artery origin stenting.

BACKGROUND: Vertebral artery origin stenting (VAOS) is the mainstream method for the treatment of vertebral artery stenosis (VAS). However, there are few studies on the risk factors analysis for residual stenosis after VAOS. PURPOSE: This study aimed to apply color Doppler ultrasound (CDU) to evaluate and analyze the risk factors of residual stenosis after VAOS. METHODS: About 178 patients with VAOS were included from 2017 to 2019 in Liuzhou worker's hospital and divided into the residual stenosis group (n = 38) and the no-residual stenosis group (n = 140). The clinical data and hemodynamics alteration before and after VAOS were collected. The univariate and multivariate logistic regression analysis was used to analyze the risk factors of residual stenosis. RESULTS: Compared with the no-residual stenosis group, the proportion of hypertension, the bending of the initial segment, and the residual stenosis length > 10 mm in the residual stenosis group were significantly higher, while the original internal diameter was significantly smaller (P < 0.05). The multivariate logistic regression analysis showed that the bending of initial segment (OR = 2.41, 95% CI: 1.32-5.45, P = 0.033), the original internal diameter (OR = 2.29, 95% CI: 1.13-5.66, P = 0.001), and the residual stenosis length > 10 mm were the risk factors of residual stenosis (OR = 2.78, 95% CI: 1.82-5.85, P = 0.044). CONCLUSION: The bending of initial segment, the original internal diameter, and the residual stenosis length > 10 mm were the risk factors of residual stenosis after VAOS.

Diagnostic accuracy of ultrasound-based multimodal radiomics modeling for fibrosis detection in chronic kidney disease.

OBJECTIVES: To predict kidney fibrosis in patients with chronic kidney disease using radiomics of two-dimensional ultrasound (B-mode) and Sound Touch Elastography (STE) images in combination with clinical features. METHODS: The Mindray Resona 7 ultrasonic diagnostic apparatus with SC5-1U convex array probe (bandwidth frequency of 1-5 MHz) was used to perform two-dimensional ultrasound and STE software. The severity of cortical tubulointerstitial fibrosis was divided into three grades: mild interstitial fibrosis and tubular atrophy (IFTA), fibrotic area < 25%; moderate IFTA, fibrotic area 26-50%; and severe IFTA, fibrotic area > 50%. After extracting radiomics from B-mode and STE images in these patients, we analyzed two classification schemes: mild versus moderate-to-severe IFTA, and mild-to-moderate versus severe IFTA. A nomogram was constructed based on multiple logistic regression analyses, combining clinical and radiomics. The performance of the nomogram for differentiation was evaluated using receiver operating characteristic (ROC), calibration, and decision curves. RESULTS: A total of 150 patients undergoing kidney biopsy were enrolled (mild IFTA: n = 74; moderate IFTA: n = 33; severe IFTA: n = 43) and randomized into training (n = 105) and validation cohorts (n = 45). To differentiate between mild and moderate-to-severe IFTA, a nomogram incorporating STE radiomics, albumin, and estimated glomerular filtration (eGFR) rate achieved an area under the ROC curve (AUC) of 0.91 (95% confidence interval [CI]: 0.85-0.97) and 0.85 (95% CI: 0.77-0.98) in the training and validation cohorts, respectively. Between mild-to-moderate and severe IFTA, the nomogram incorporating B-mode and STE radiomics features, age, and eGFR achieved an AUC of 0.93 (95% CI: 0.89-0.98) and 0.83 (95% CI: 0.70-0.95) in the training and validation cohorts, respectively. Finally, we performed a decision curve analysis and found that the nomogram using both radiomics and clinical features exhibited better predictability than any other model (DeLong test, p < 0.05 for the training and validation cohorts). CONCLUSION: A nomogram based on two-dimensional ultrasound and STE radiomics and clinical features served as a non-invasive tool capable of differentiating kidney fibrosis of different severities. KEY POINTS: • Radiomics calculated based on the ultrasound imaging may be used to predict the severities of kidney fibrosis. • Radiomics may be used to identify clinical features associated with the progression of tubulointerstitial fibrosis in patients with CKD. • Non-invasive ultrasound imaging-based radiomics method with accuracy aids in detecting renal fibrosis with different IFTA severities.

Removal of Per-, Poly-fluoroalkyl substances (PFASs) and multi-biosphere community dynamics in a bacteria-algae symbiotic aquatic ecosystem.

The presence of Per-, Poly-fluoroalkyl substances (PFASs) in aquatic ecosystems has drawn broad concerns in the scientific community due to their biological toxicity. However, little has been explored regarding PFASs' removal in phytoplankton-dominated environments. This study aimed to create a simulated bacteria-algae symbiotic ecosystem to observe the potential transportation of PFASs. Mass distributions showed that sand (63-2000 µm), silt & clay (0-63 µm), the phycosphere (>3 µm plankton), and the free-living biosphere (0.22-3 µm plankton) contained 19.00, 7.78, 5.73 and 2.75% PFASs in their total mass, respectively. Significant correlations were observed between carbon chain lengths and removal rates (R2 = 0.822, p < 10-4). Structural equation models revealed potential PFAS transportation pathways, such as water-phycosphere- free-living biosphere-sand-silt&clay, and water-sand-silt&clay (p < 0.05). The presence of PFASs decreased the bacterial density but increased algal density (p < 0.01) in the planktonic environment, and PFASs with longer carbon chain lengths showed a stronger enhancement in microbial community successions (p < 0.05). In algal metabolisms, chlorophyll-a and carotenoids were the key pigments that resisted reactive oxygen species caused by PFASs. PFBA (perfluorobutyric acid) (10.38-14.68%) and PFTeDA (perfluorotetradecanoic acid) (10.33-15.96%) affected bacterial metabolisms in phycosphere the most, while in the free-living biosphere was most effected by PFPeA (perfluorovaleric acid) (13.21-13.99%) and PFDoA (perfluorododecanoic acid) (10.04-10.50%). The results of this study provide new guidance measures for PFAS removal and management in aquatic environments.

Label-free electrochemical biosensor for determination of procalcitonin based on graphene-wrapped Co nanoparticles encapsulated in carbon nanobrushes coupled with AuPtCu nanodendrites.

A new label-free electrochemical immunosensor was constructed for quantitative detection of procalcitonin (PCT), by employing AuPtCu nanodendrites (AuPtCu NDs, prepared by a one-pot solvothermal method) and graphene-wrapped Co nanoparticles encapsulated in 3D N-doped carbon nanobrushes (G-Co@ NCNBs), obtained by self-catalyzed chemical vapor deposition as immune-sensing platform. Impressively, the home-made nanocomposite enlarged the highly accessible active sites and promoted the mass/electron transport, in turn showing the efficient synergistic catalysis towards H2O2 reduction, combined by greatly increasing the loading capacity of the PCT antibody (Ab). The as-constructed sensor displayed a dynamic linear range of 0.0001 ~ 100 ng mL-1 along with an ultra-low limit of detection (LOD = 0.011 pg mL-1, S/N = 3) and was further explored for determination of PCT in a diluted serum sample with acceptable results. The sensor provides some valuable guidelines for bioassay and early diagnosis of sepsis.

A label-free electrochemical immnunosensor based on signal magnification of oxygen reduction reaction catalyzed by uniform PtCo nanodendrites for highly sensitive detection of carbohydrate antigen 15-3.

Developing a highly sensitive immunoassay for tumor biomarkers is particularly important in bioanalysis and early disease diagnosis. In this work, a simple one-pot solvothermal method was developed for controllable synthesis of well-dispersed PtCo alloyed nanodendrites (PtCo NDs) by using l-carnosine as the co-structure-directing agent. The PtCo NDs had a large specific surface area and provided abundant active sites available for electrocatalytic oxygen reduction reaction (ORR). Based on the highly enhanced currents of the ORR, a novel label-free electrochemical immunosensor was fabricated for highly sensitive assay of carbohydrate antigen 15-3 (CA15-3). The sensor showed a wide linear range of 0.1-200 U mL-1 and a low limit of detection (LOD) down to 0.0114 U mL-1 (S/N = 3), in turn exploring its application to diluted human serum samples with satisfactory results. This study provides a feasible platform for monitoring other tumor markers in clinical diagnosis.

Discovery of ß-arrestin-biased ß2-adrenoceptor agonists from 2-amino-2-phenylethanol derivatives.

ß-Arrestins are a small family of proteins important for signal transduction at G protein-coupled receptors (GPCRs). ß-Arrestins are involved in the desensitization of GPCRs. Recently, biased ligands possessing different efficacies in activating the G protein- versus the ß-arrestin-dependent signals downstream of a single GPCR have emerged, which can be used to selectively modulate GPCR signal transduction in such a way that desirable signals are enhanced to produce therapeutic effects while undesirable signals of the same GPCR are suppressed to avoid side effects. In the present study, we evaluated agonist bias for compounds developed along a drug discovery project of ß2-adrenoceptor agonists. About 150 compounds, including derivatives of fenoterol, 2-amino-1-phenylethanol and 2-amino-2-phenylethanol, were obtained or synthesized, and initially screened for their ß-adrenoceptor-mediated activities in the guinea pig tracheal smooth muscle relaxation assay or the cardiomyocyte contractility assay. Nineteen bioactive compounds were further assessed using both the HTRF cAMP assay and the PathHunter ß-arrestin assay. Their concentration-response data in stimulating cAMP synthesis and ß-arrestin recruitment were applied to the Black-Leff operational model for ligand bias quantitation. As a result, three compounds (L-2, L-4, and L-12) with the core structure of 5-(1-amino-2-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one were identified as a new series of ß-arrestin-biased ß2-adrenoceptor agonists, whereas salmeterol was found to be Gs-biased. These findings would facilitate the development of novel drugs for the treatment of both heart failure and asthma.

[Recent advances in study of long ß(2)-adrenoceptor agonist].

ß2-Adrenoceptor agonists are highly effective bronchodilators and are widely used in the treatment of both chronic obstructive pulmonary disease (COPD) and asthma. In the last 15 years, there has been great interest within the pharmaceutical industry in the discovery of a long ß2-adrenoceptor agonist for a mono-therapy or combination therapy. The search for new long-acting ß2-adrenoreceptor agonists (LABA's), for the treatment of asthma and COPD, has become a very active area of drug discovery. This article reviews the mechanisms, potential candidates and research advances of long ß2-adrenoceptor agonists.