A fully automatic deep learning-based method for segmenting regions of interest and predicting renal function in pediatric dynamic renal scintigraphy.

OBJECTIVE: Accurate delineation of renal regions of interest (ROIs) is critical for the assessment of renal function in pediatric dynamic renal scintigraphy (DRS). The purpose of this study was to develop and evaluate a deep learning (DL) model that can fully automatically delineate renal ROIs and calculate renal function in pediatric 99mTechnetium-ethylenedicysteine (99mTc-EC) DRS. METHODS: This study retrospectively analyzed 1,283 pediatric DRS data at a single center from January to December 2018. These patients were divided into training set (n = 1027), validation set (n = 128), and testing set (n = 128). A fully automatic segmentation of ROIs (FASR) model was developed and evaluated. The pixel values of the automatically segmented ROIs were calculated to predict renal blood perfusion rate (BPR) and differential renal function (DRF). Precision, recall rate, intersection over union (IOU), and Dice similarity coefficient (DSC) were used to evaluate the performance of FASR model. Intraclass correlation (ICC) and Pearson correlation analysis were used to compare the consistency of automatic and manual method in assessing the renal function parameters in the testing set. RESULTS: The FASR model achieved a precision of 0.88, recall rate of 0.94, IOU of 0.83, and DSC of 0.91. In the testing set, the r values of BPR and DRF calculated by the two methods were 0.94 (P < 0.01) and 0.97 (P < 0.01), and the ICCs (95% confidence interval CI) were 0.94 (0.90-0.96) and 0.94 (0.91-0.96). CONCLUSION: We propose a reliable and stable DL model that can fully automatically segment ROIs and accurately predict renal function in pediatric 99mTc-EC DRS.

Nicotine Activating α4ß2 Nicotinic Acetylcholine Receptors to Suppress Neuroinflammation via JAK2-STAT3 Signaling Pathway in Ischemic Rats and Inflammatory Cells.

Nicotine plays a role in inhibiting inflammatory factors, which contributes to improving cognitive impairment by activating α4ß2 nAChRs in ischemic rats, but the underlying mechanism has not been fully elucidated. Janus tyrosine kinase 2-signal transducer and activator of transcription 3 (JAK2-STAT3) signaling pathway is involved in cognitive improvement, and there seems to be a relationship between nAChRs and JAK2-STAT3 as well. The aim of this study is to explore the role of JAK2-STAT3 signaling pathway in nicotine-mediated anti-inflammatory effect. Nicotine, DHßE (the strongest competitive antagonist of α4ß2 nAChRs), and AG490 (a specific JAK2-STAT3 blocker) were used to intervene and treat ischemic rats and HEK-293 T-hα4ß2 cells. The Morris water maze (MWM) test and 2-[18F]-A-85380 PET imaging were performed to detect the cognitive function and α4ß2 nAChRs density in ischemic rats. The results demonstrated that nicotine intervention increased the density of α4ß2 nAChRs and improved cognitive impairment, but this effect was blocked by AG490, and the receptors were still upregulated. Essentially, when the JAK2-STAT3 signaling pathway was blocked, nicotine could only upregulate the expression of α4ß2 nAChRs, but not improve the cognitive function. PCR and Western blot analysis further confirmed these results. The cell experiments also showed that nicotine could reduce inflammatory factors stimulated by LPS and upregulate the expression of pJAK2 and pSTAT3 in HEK-293 T-hα4ß2 cells, while AG490 and DHßE reversed the effect of nicotine. To sum up, our work indicated that JAK2-STAT3 signaling pathway played an important role in nicotine-induced cognitive improvement by upregulating α4ß2 nAChRs in ischemic rats.

Neuroprotective effect of combined use of nicotine and celecoxib by inhibiting neuroinflammation in ischemic rats.

INTRODUCTION: The contribution of neuroinflammation in cognitive impairment is increasingly recognized. Non-steroidal anti-inflammatory drugs had been proven that it could improve cognitive impairment in large dose but with more side effect, which limited the application. The main objective of this study was to investigate whether the combined use of nicotine and celecoxib could obtain synergistic neuroprotective effect in ischemic rats. METHODS: Twenty adult Sprague-Dawley (SD) rats underwent ischemic model surgery by injecting endothelin-1 into the left thalamus, which were classified into four groups with different interventions: nicotine (1.5 mg/kg/d), celecoxib (15 mg/kg/d), nicotine (1.5 mg/kg/d) +celecoxib (15 mg/kg/d), or saline after surgery. The other five SD rats also underwent same surgery by injecting saline instead of endothelin-1, as the control group. Morris water maze (MWM) test was adopted to assess the cognition. Micro PET/CT with 2-[18F]-A-85380 were performed for α4ß2-nAChRs detection in vivo. Western blot, real-time PCR and immunohistochemical staining were adopted to detect the expression of α4ß2-nAChRs and inflammatory factors which included TNF-α, IL-1ß, IL-6 in brain tissue. Microglial activation in the brain was monitored by immunofluorescence with IBA1 staining. RESULTS: The MWM test showed rats given with nicotine or celecoxib alone showed much better memory than rats with saline, no difference was observed between nicotine and celecoxib. The rat memory was recovered most significant when the nicotine and celecoxib were combined (p < 0.05). Micro-PET/CT showed much more tracer uptake in the left thalamus and whole brain in rats given with nicotine, or nicotine + celecoxib (nico + cele group) than saline treated rats, whereas the rats given celecoxib did not. Compared with saline treated rats, we found the proteins of α4nAChR and ß2nAChR in rats given nicotine or nico + cele increased significantly, and mRNA/proteins of TNF-α, IL-1ß and IL-6 decreased at the same time. The α 4nAChR and ß 2nAChR proteins in rats given celecoxib is the same as saline treated rats, whereas the inflammatory factors decreased obviously compared with saline treated rats. Microglial activation was confirmed in saline treated rats, which was inhibited in rats give nicotine, celecoxib or both. CONCLUSIONS: The study revealed the combined use of nicotine and celecoxib may improve the cognitive function in ischemic rats, with a better effect than either alone. Both nicotine and celecoxib can inhibit inflammation, but through different mechanisms: nicotine can activate α4ß2-nAChRs while celecoxib is cyclooxygenase-2 inhibitor. Our findings suggest the combined application of two drugs with different anti-inflammation mechanism could attenuate cognitive impairment more effectively in ischemic rats, which may hold therapeutic potential in the clinical practice.