1.RXRα modulates hepatic stellate cell activation and liver fibrosis by targeting CaMKKβ-AMPKα axis.
Lijun CAI ; Meimei YIN ; Shuangzhou PENG ; Fen LIN ; Liangliang LAI ; Xindao ZHANG ; Lei XIE ; Chuanying WANG ; Huiying ZHOU ; Yunfeng ZHAN ; Gulimiran ALITONGBIEKE ; Baohuan LIAN ; Zhibin SU ; Tenghui LIU ; Yuqi ZHOU ; Zongxi LI ; Xiaohui CHEN ; Qi ZHAO ; Ting DENG ; Lulu CHEN ; Jingwei SU ; Luoyan SHENG ; Ying SU ; Ling-Juan ZHANG ; Fu-Quan JIANG ; Xiao-Kun ZHANG
Acta Pharmaceutica Sinica B 2025;15(7):3611-3631
Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl4 and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.
2.Application of high resolution magnetic resonance imaging in intracranial atherosclerosis
International Journal of Cerebrovascular Diseases 2023;31(10):756-761
Intracranial atherosclerotic stenosis (ICAS) is the main cause of patients with stroke in China. How to accurately detect and identify vulnerable plaques through imaging examinations, and strengthen the prediction and prevention of ischemic stroke in patients with ICAS, is a key clinical problem that needs to be solved, and is also a current challenge. With the application of magnetic resonance vascular wall imaging in ICAS, imaging examinations provide useful information on the vascular structure and plaque stability at the stenosis in addition to the degree of stenosis. It has improved the ability to evaluate ICAS and promoted its development towards more accurate diagnosis and treatment.
3.CT characteristics and treatment options of spontaneous isolated dissection of celiac artery:a single-center experience
Di ZHANG ; Mingxu JIN ; Xinying WU ; Haobo SU ; Jianping GU ; Xindao YIN ; Liping WANG
Journal of Practical Radiology 2023;39(12):1957-1961
Objective To analyze the demographic data,CT characteristics,treatment methods and follow-up results of patients with spontaneous isolated dissection of celiac artery(SIDCA)and to explore the selection of treatment strategy for SIDCA.Methods Medical records of 31 patients diagnosed as SIDCA were selected.The patients were divided into 2 groups,symptomatic group and asymptotic group.Demographic data,morbidity season,CT characteristics(type,distance of the entry site from the origin of the artery,dissection length,compression rate of the true lumen,branches involvement,organ ischemia,coexisting vasculopathy),treatment methods,and follow-up results were analyzed.Results Thirty-one patients were identified by CT contrast scan,22 were symptomatic and 9 were asymptomatic.22 patients were first diagnosed in cooler season,compared with 9 patients in warmer season(22 vs 9,Fisher's exact test,P=0.029).The difference between symptomatic and asymptomatic groups about branches involvement in patients was significant(8/14 vs 0/9,Fisher's exact test,P=0.007).Treatment included observation in 24,endovascular intervention in 6 patients and surgical repair in 1 patient.No patient required bowel resection.The mean follow-up period was 13.75 months.Except for 2 patients,the condition of the remaining patients improved or stabilized during follow-up.Conclusion The difference between symptomatic and asymptomatic groups about branches involvement in patients is significant.Initial conservative treatment may be adequate for patients without end organ malperfusion or aneurysm formation or aneurysm rupture in SIDCA.Additionally,during the cooler season,visceral artery should be observed carefully on abdominal contrast CT,especially in the patient with abdominal pain,to avoid misdiagnosis.
4.Correlation between vascular wall shear stress and stenosis degree and plaque characteristics in patients with atherosclerotic stenosis in the middle brain
Siyu WANG ; Danfeng ZHANG ; Qiuyue ZHAO ; Xindao YIN
Chinese Journal of Neurology 2022;55(6):612-618
Objective:To investigate the relationship between wall shear stress (WSS) and the degree of lumen stenosis and plaque characteristics in patients with atherosclerotic stenosis in the middle brain.Methods:Thirty-four patients with moderate to severe unilateral middle cerebral artery stenosis in Nanjing First Hospital from June 2020 to June 2021 were analyzed retrospectively. All patients underwent routine magnetic resonance imaging and vascular wall imaging to obtain plaque parameters such as plaque area, remodeling mode and remodeling index. Based on magnetic resonance angiography, a computational fluid dynamics model was established to simulate the local hemodynamics near the lesion and quantify WSS. The patients were divided into high WSS group and low WSS group according to the median WSS. The differences of clinical baseline data, degree of lumen stenosis and plaque characteristics between the two groups were compared. Pearson correlation analysis was used to calculate the correlation between WSS and lumen stenosis and plaque characteristics.Results:A total of 34 patients were included in this study, 17 in the high WSS group and 17 in the low WSS group. Compared with the low WSS group, the plasma homocysteine level in the high WSS group was lower [(11.10±4.96) μmol/L vs (16.97±6.98) μmol/L, t=-2.83, P=0.010], the degree of stenosis was lower (0.56±0.05 vs 0.66±0.08, t=-4.54, P<0.001), and the proportion of positive lumen remodeling was higher (12/17 vs 4/17, P=0.015). Pearson correlation analysis showed that the degree of lumen stenosis was negatively correlated with WSS ( r=-0.44, P=0.011), and the plaque area was not correlated with WSS. Conclusions:WSS in middle cerebral artery stenosis is related to the degree of lumen stenosis and the mode of vascular remodeling. Higher WSS has poor stability, but lower WSS is more likely to cause lumen stenosis.
5.Hemodynamic evaluation of intracranial atherosclerotic lesions based on computational fluid dynamics
Siyu WANG ; Danfeng ZHANG ; Junshan ZHOU ; Xindao YIN
International Journal of Cerebrovascular Diseases 2021;29(6):471-475
Intracranial atherosclerotic lesions are a common cause of ischemic stroke. Hemodynamics plays an important role in the formation and development of atherosclerosis and the risk assessment of clinical ischemic stroke events. As an evaluation method of cerebral hemodynamics, computational fluid dynamics can intuitively obtain hemodynamic parameters and provide valuable information for clinical diagnosis and treatment. This article reviews the application progress of computational fluid dynamics in evaluating peripheral hemodynamics of intracranial atherosclerotic lesions.
6.Automatic Detection and Classification of Rib Fractures on Thoracic CT Using Convolutional Neural Network: Accuracy and Feasibility
Qing-Qing ZHOU ; Jiashuo WANG ; Wen TANG ; Zhang-Chun HU ; Zi-Yi XIA ; Xue-Song LI ; Rongguo ZHANG ; Xindao YIN ; Bing ZHANG ; Hong ZHANG
Korean Journal of Radiology 2020;21(7):869-879
Objective:
To evaluate the performance of a convolutional neural network (CNN) model that can automatically detect and classify rib fractures, and output structured reports from computed tomography (CT) images.
Materials and Methods:
This study included 1079 patients (median age, 55 years; men, 718) from three hospitals, between January 2011 and January 2019, who were divided into a monocentric training set (n = 876; median age, 55 years; men, 582), five multicenter/multiparameter validation sets (n = 173; median age, 59 years; men, 118) with different slice thicknesses and image pixels, and a normal control set (n = 30; median age, 53 years; men, 18). Three classifications (fresh, healing, and old fracture) combined with fracture location (corresponding CT layers) were detected automatically and delivered in a structured report. Precision, recall, and F1-score were selected as metrics to measure the optimum CNN model. Detection/diagnosis time, precision, and sensitivity were employed to compare the diagnostic efficiency of the structured report and that of experienced radiologists.
Results:
A total of 25054 annotations (fresh fracture, 10089; healing fracture, 10922; old fracture, 4043) were labelled for training (18584) and validation (6470). The detection efficiency was higher for fresh fractures and healing fractures than for old fractures (F1-scores, 0.849, 0.856, 0.770, respectively, p = 0.023 for each), and the robustness of the model was good in the five multicenter/multiparameter validation sets (all mean F1-scores > 0.8 except validation set 5 [512 x 512 pixels; F1-score = 0.757]). The precision of the five radiologists improved from 80.3% to 91.1%, and the sensitivity increased from 62.4% to 86.3% with artificial intelligence-assisted diagnosis. On average, the diagnosis time of the radiologists was reduced by 73.9 seconds.
Conclusion
Our CNN model for automatic rib fracture detection could assist radiologists in improving diagnostic efficiency, reducing diagnosis time and radiologists’ workload.
7.Relationship between remodeling patterns and plaque enhancement in patients with symptomatic atherosclerotic middle cerebral artery stenosis
Danfeng ZHANG ; Wen GENG ; Tingting ZHI ; Xindao YIN ; Xinying WU
International Journal of Cerebrovascular Diseases 2018;26(3):184-188
Objective To investigate the relationship between vascular remodeling patterns of atherosclerotic middle cerebral artery (MCA) stenosis and plaque enhancement.Methods From August 2015 to June 2016,patients with unilateral symptomatic atherosclerotic MCA stenosis underwent routine MRI and black blood magnetic resonance inaging examinations.The vessel area and lumen area of MCA at the site of atherosclerotic MCA stenosis were measured,and the degree of MCA stenosis and the remodeling index were calculated.Results A total of 33 patients were included.Eleven had obvious plaque enhancement,including 9 positive remodeling and 2 negative remodeling;22 did not have plaque enhancement,including 5 positive remodeling,5 no remodeling,and 12 negative remodeling.The obvious plaque enhancement group was mainly positive remodeling (81.8% vs.22.7%),and the no obvious enhancement group was mainly negative remodeling (54.5% vs.18.2%).The difference was statistically significant (P=0.018).Conclusion Plaque enhancement at the site of atherosclerotic MCA stenosis is mainly positive remodeling,which reflects plaque instability.
8.Benign and malignant classification of renal occupancy lesions CT images using convolutional neural networks
Leilei ZHOU ; Zuoheng ZHANG ; Yuchen CHEN ; Jingjing FU ; Xindao YIN ; Hongbing JIANG
International Journal of Biomedical Engineering 2018;41(5):417-422
Objective To investigate the feasibility and application value of the benign and malignant classificational methods of renal occupying CT images based on convolutional neural networks (CNN). Methods An image omics method that can automatically learn the image features and classify CT images was used. Firstly, the CNN model obtained by large-scale natural image training was used to migrate the characteristics of the renal occupancy lesions CT images, and then the fine-tuning of the full connection layer was used to realize the benign and malignant classification of the images. Results The evaluation indexes of the VGG19 model were lower than ResNet50 and Inception V3, and the training result showed obvious overfitting. The accuracy, sensitivity and negative prediction values of the Inception V3 model was 93.8%, 99.5% and 99.1%, respectively, which were higher than that of the ResNet50 model. Conclusions The benign and malignant classification of renal occupancy lesions CT images using CNN is a reasonable and feasible method, and the fine-tuned Inception V3 model has a better classification performance.
9.Clinical value of dual-energy CT Volume software in quantitative analysis of urate crystals
Yamei ZHANG ; Hui XU ; Qian CHEN ; Xindao YIN ; Xingguo CHEN ; Quan XU ; Di ZHANG
Journal of Practical Radiology 2017;33(4):608-610,628
Objective To assess the clinical value of dual-energy CT (DECT) Volume software in quantitative analysis of urate crystals.Methods The DECT data of 60 gout patients based on the American College of Rheumatology diagnostic criteria were analyzed retrospectively.The volumes of urate crystals were quantitatively analyzed by using Volume software with two senior radiologists.The results were statistically analyzed.Results Seventy-two joints of 60 gout patients were scanned by DECT.40 of 43 joints had urate crystals in foot and ankle with the average volume of (0.621±0.742) cm3;18 of 19 joints had urate crystals in knee with the average volume of (0.842±1.086) cm3;10 of 10 joints had urate crystals in hand and wrist with the average volume of (0.796±0.583) cm3.There was no statistical difference for volume measurement between two doctors (P>0.05).The volumes of urate crystals in 4 patients with regular medication were reduced.Conclusion Volume software of DECT can quantitatively analyze urate crystals with a good repeatability, which has high application value in clinical diagnosis and treatment monitoring of gout.
10.Effect of intensive blood pressure reduction on peri-hematomal secondary neuronal injury and prognosis in patients with intracerebral hemorrhage
Hong ZHANG ; Jie YANG ; Xindao YIN ; Qingqing XU ; Junshan ZHOU
Chinese Journal of Nervous and Mental Diseases 2015;(3):129-134
Objective To study the influence of early intensive blood pressure (BP) lowering treatment on peri-he?matomal secondary neuronal injury and prognosis after acute intracerebral hemorrhage. Methods A randomised con?trolled trial consisting of 36 consecutive patients within 6 h of intracerebral hemorrhage onset were randomly assigned to intensive BP lowering group and guideline BP lowering group. All patients underwent MR spectroscopy at 72 h and were followed up 90 days. N Acetyl Aspartate/Creatine (NAA/Cr) and lactic acid wave around peri-hematomal at 72 h, neuro?logic function at early stage, and death and/or disability at 90d were compared between these two group. Results Spec?trum lines were obtained from thirty-one patients:14 from intensive BP lowing group and 17 from guideline BP lowering group. There was no significant difference in the percentage declines of NAA/Cr at 72 h between the two groups (13.3%± 4.2% vs. 11.9%± 2.8%, P = 0.308). There was no statistical differences either in neurologic function at 7 d or in death and/or disability at 90 d (P>0.05). Conclusions Early intensive BP-lowering treatment had no role on peri-hematomal secondary neuronal injury and prognosis after acute intracerebral hemorrhage. Further high-quality and large-scale ran?domised controlled trial are necessary to verify this result.

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