Publications by authors named "Ning Bin"

56 Publications

Down-regulating Circular RNA Prkcsh suppresses the inflammatory response after spinal cord injury.

Neural Regen Res 2022 Jan;17(1):144-151

Department of Orthopedics, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong Province, China.

Circular RNAs (circRNAs) are a class of conserved, endogenous non-coding RNAs that are involved in transcriptional and post-transcriptional gene regulation and are highly enriched in the nervous system. They participate in the survival and differentiation of multiple nerve cells, and may even promote the recovery of neurological function after stroke. However, their role in the inflammatory response after spinal cord injury remains unclear. In the present study, we established a mouse model of T9 spinal cord injury using the modified Allen's impact method, and identified 16,013 circRNAs and 960 miRNAs that were differentially expressed after spinal cord injury. Of these, the expression levels of circPrkcsh were significantly different between injured and sham-treated mice. We then treated astrocytes with tumor necrosis factor-α in vitro to simulate the inflammatory response after spinal cord injury. Our results revealed an elevated expression of circPrkcsh with a concurrent decrease in miR-488 expression in injured cells. We also found that circPrkcsh regulated the expression of the inflammation-related gene Ccl2. Furthermore, in tumor necrosis factor-α-treated astrocytes, circPrkcsh knockdown decreased the expression of Ccl2 by upregulating miR-488 expression, and reduced the secretion of inflammatory cytokines in vitro. These findings suggest that differentially expressed circRNAs participate in the inflammatory response after spinal cord injury and act as the regulators of certain microRNAs. Furthermore, circPrkcsh may be used as an miR-488 sponge to regulate Ccl2 expression, which might provide a new potential therapy for SCI. The study was approved by the Animal Ethics Committee of Shandong University of China (approval No. KYLL-20170303) on March 3, 2017.
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http://dx.doi.org/10.4103/1673-5374.314114DOI Listing
January 2022

Thrombus aspiration during primary percutaneous coronary intervention improved outcome in patients with STEMI and a large thrombus burden.

J Int Med Res 2021 May;49(5):3000605211012611

Department of Cardiology Center, Hebei General Hospital, Shijiazhuang, No.348 West Peace Road, Xinhua District, Shijiazhuang, Hebei Province, People's Republic of China.

Background: The benefit of thrombus aspiration (TA) during primary percutaneous coronary intervention (PPCI) to patients with ST-segment elevation myocardial infarction (STEMI) remains controversial. This study aimed to assess TA's impact on the outcome and prognosis for patients with STEMI and a large thrombus burden during PPCI.

Methods: This retrospective study evaluated consecutive patients with STEMI and a large thrombus burden (thrombolysis in myocardial infraction [TIMI] thrombus grade ≥4) who underwent conventional PPCI (n = 126) or PPCI + TA (n = 208) between February 2017 and January 2019. The procedure outcome and clinical prognosis were compared.

Results: Postprocedural vessel diameter was larger, and corrected TIMI frame count (cTFC) was lower in the PPCI + TA compared with the PPCI group. The proportion of postprocedural TIMI 3 flow was 83.3% in the PPC group and 94.2% in the PPCI+TA group. During the 12-month follow-up, no significant differences existed in the incidence of cardiac death, reinfarction, stent thrombosis, target vessel revascularization, or stroke.

Conclusion: Application of TA in patients with STEMI and a large thrombus burden during PPCI may improve the procedural outcome, but it showed no benefit on the clinical prognosis in the 12-month follow-up. Longer follow-up studies are needed to confirm TA's clinical implications in patients with STEMI.
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http://dx.doi.org/10.1177/03000605211012611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113933PMC
May 2021

Asenapine maleate inhibits angiotensin II-induced proliferation and activation of cardiac fibroblasts via the ROS/TGFβ1/MAPK signaling pathway.

Biochem Biophys Res Commun 2021 05 24;553:172-179. Epub 2021 Mar 24.

Research Center for Translational Medicine, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China; Research Center for Translational Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, China. Electronic address:

Background: Cardiac fibrosis will increase wall stiffness and diastolic dysfunction, which will eventually lead to heart failure. Asenapine maleate (AM) is widely used in the treatment of schizophrenia. In the current study, we explored the potential mechanism underlying the role of AM in angiotensin II (Ang II)-induced cardiac fibrosis.

Methods: Cardiac fibroblasts (CFs) were stimulated using Ang II with or without AM. Cell proliferation was measured using the cell counting kit-8 assay and the Cell-Light EdU Apollo567 In Vitro Kit. The expression levels of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA) were detected using immunofluorescence or western blotting. At the protein level, the expression levels of the components of the transforming growth factor beta 1 (TGFβ1)/mitogen-activated protein kinase (MAPK) signaling pathway were also detected.

Results: After Ang II stimulation, TGFβ1, TGFβ1 receptor, α-SMA, fibronectin (Fn), collagen type I (Col1), and collagen type III (Col3) mRNA levels increased; the TGFβ1/MAPK signaling pathway was activated in CFs. After AM pretreatment, cell proliferation was inhibited, the numbers of PCNA -positive cells and the levels of cardiac fibrosis markers decreased. The activity of the TGFβ1/MAPK signaling pathway was also inhibited. Therefore, AM can inhibit cardiac fibrosis by blocking the Ang II-induced activation through TGFβ1/MAPK signaling pathway.

Conclusions: This is the first report to demonstrate that AM can inhibit Ang II-induced cardiac fibrosis by down-regulating the TGFβ1/MAPK signaling pathway. In this process, AM inhibited the proliferation and activation of CFs and reduced the levels of cardiac fibrosis markers. Thus, AM represents a potential treatment strategy for cardiac fibrosis.
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http://dx.doi.org/10.1016/j.bbrc.2021.03.042DOI Listing
May 2021

Deep learning applied to two-dimensional color Doppler flow imaging ultrasound images significantly improves diagnostic performance in the classification of breast masses: a multicenter study.

Chin Med J (Engl) 2021 Jan 7;134(4):415-424. Epub 2021 Jan 7.

Department of Ultrasound, Beijing Tian Tan Hospital, Capital Medical University, Beijing 100070, China.

Background: The current deep learning diagnosis of breast masses is mainly reflected by the diagnosis of benign and malignant lesions. In China, breast masses are divided into four categories according to the treatment method: inflammatory masses, adenosis, benign tumors, and malignant tumors. These categorizations are important for guiding clinical treatment. In this study, we aimed to develop a convolutional neural network (CNN) for classification of these four breast mass types using ultrasound (US) images.

Methods: Taking breast biopsy or pathological examinations as the reference standard, CNNs were used to establish models for the four-way classification of 3623 breast cancer patients from 13 centers. The patients were randomly divided into training and test groups (n = 1810 vs. n = 1813). Separate models were created for two-dimensional (2D) images only, 2D and color Doppler flow imaging (2D-CDFI), and 2D-CDFI and pulsed wave Doppler (2D-CDFI-PW) images. The performance of these three models was compared using sensitivity, specificity, area under receiver operating characteristic curve (AUC), positive (PPV) and negative predictive values (NPV), positive (LR+) and negative likelihood ratios (LR-), and the performance of the 2D model was further compared between masses of different sizes with above statistical indicators, between images from different hospitals with AUC, and with the performance of 37 radiologists.

Results: The accuracies of the 2D, 2D-CDFI, and 2D-CDFI-PW models on the test set were 87.9%, 89.2%, and 88.7%, respectively. The AUCs for classification of benign tumors, malignant tumors, inflammatory masses, and adenosis were 0.90, 0.91, 0.90, and 0.89, respectively (95% confidence intervals [CIs], 0.87-0.91, 0.89-0.92, 0.87-0.91, and 0.86-0.90). The 2D-CDFI model showed better accuracy (89.2%) on the test set than the 2D (87.9%) and 2D-CDFI-PW (88.7%) models. The 2D model showed accuracy of 81.7% on breast masses ≤1 cm and 82.3% on breast masses >1 cm; there was a significant difference between the two groups (P < 0.001). The accuracy of the CNN classifications for the test set (89.2%) was significantly higher than that of all the radiologists (30%).

Conclusions: The CNN may have high accuracy for classification of US images of breast masses and perform significantly better than human radiologists.

Trial Registration: Chictr.org, ChiCTR1900021375; http://www.chictr.org.cn/showproj.aspx?proj=33139.
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http://dx.doi.org/10.1097/CM9.0000000000001329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7909320PMC
January 2021

The 26S Proteasome Regulatory Subunit GmPSMD Promotes Resistance to in Soybean.

Front Plant Sci 2021 28;12:513388. Epub 2021 Jan 28.

Key Laboratory of Soybean Biology of Chinese Education Ministry, Soybean Research Institute, Northeast Agricultural University, Harbin, China.

Phytophthora root rot, caused by is a destructive disease of soybean () worldwide. We previously confirmed that the bHLH transcription factor GmPIB1 (-inducible bHLH transcription factor) reduces accumulation of reactive oxygen species (ROS) in cells by inhibiting expression of the peroxidase-related gene thus improving the resistance of hairy roots to . To identify proteins interacting with GmPIB1 and assess their participation in the defense response to , we obtained transgenic soybean hairy roots overexpressing GmPIB1 by mediated transformation and examined GmPIB1 protein-protein interactions using immunoprecipitation combined with mass spectrometry. We identified 392 proteins likely interacting with GmPIB1 and selected 20 candidate genes, and only 26S proteasome regulatory subunit GmPSMD (Genbank accession no. XP_014631720) interacted with GmPIB1 in luciferase complementation and pull-down experiments and yeast two-hybrid assays. Overexpression of (OE) in soybean hairy roots remarkably improved resistance to and RNA interference of ( -RNAi) increased susceptibility. In addition, accumulation of total ROS and hydrogen peroxide (HO) in OE transgenic soybean hairy roots were remarkably lower than those of the control after infection. Moreover, in -RNAi transgenic soybean hairy roots, HO and the accumulation of total ROS exceeded those of the control. There was no obvious difference in superoxide anion (O) content between control and transgenic hairy roots. Antioxidant enzymes include peroxidase (POD), glutathione peroxidase (GPX), superoxide dismutase (SOD), catalase (CAT) are responsible for ROS scavenging in soybean. The activities of these antioxidant enzymes were remarkably higher in -OE transgenic soybean hairy roots than those in control, but were reduced in -RNAi transgenic soybean hairy roots. Moreover, the activity of 26S proteasome in -OE and -OE transgenic soybean hairy roots was significantly higher than that in control and was significantly lower in -RNAi soybean hairy roots after infection. These data suggest that might reduce the production of ROS by improving the activity of antioxidant enzymes such as POD, SOD, GPX, CAT, and plays a significant role in the response of soybean to . Our study reveals a valuable mechanism for regulation of the pathogen response by the 26S proteasome in soybean.
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http://dx.doi.org/10.3389/fpls.2021.513388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876454PMC
January 2021

Inconsistency of Bone Mineral Density Between Femoral Head and Proximal Femur After Femoral Neck Fracture Surgery Indicates Great Possibility of Femoral Head Necrosis.

Orthopedics 2021 Mar-Apr;44(2):e223-e228. Epub 2020 Dec 30.

On clinical observation, it was found that the bone mineral density (BMD) of the femoral head and proximal femur was not consistent in some patients with femoral neck fracture after surgery. The current study was performed to explore whether this phenomenon was associated with femoral head necrosis after surgery for femoral neck fracture. Bone mineral density inconsistency is when the difference of the sum of pixel values on both sides of the fracture line has exceeded 30%. Statistical analysis was performed on the clinical characteristics of 271 patients who had received the operation for femoral neck fracture. Chi-square test, Spearman rank correlation, independent sample test, Kaplan-Meier method, and log-rank test, as well as univariate Cox regression and multivariate Cox regression, were used to analyze the potential relationship among related factors. It was revealed that the incidence of inconsistency in BMD between the femoral head and proximal femur was significantly increased in patients with femoral head necrosis after surgery for femoral neck fracture, and that the consistency was considerably high between BMD inconsistency and femoral head necrosis. The inconsistent BMD occurred 11.1 months earlier than the necrosis of the femoral head. Cox multivariate regression analysis indicated that the inconsistency in BMD between the femoral head and proximal femur after surgery for femoral neck fracture was an independent prognostic factor affecting femoral head necrosis. The inconsistent changes in BMD between the femoral head and proximal femur after surgery for femoral neck fracture indicate a great possibility of femoral head necrosis. [. 2021;44(2):e223-e228.].
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http://dx.doi.org/10.3928/01477447-20201216-06DOI Listing
December 2020

A Multi-Source Data Fusion Framework for Revealing the Regulatory Mechanism of Breast Cancer Immune Evasion.

Front Genet 2020 12;11:595324. Epub 2020 Nov 12.

College of Computer Science and Electronic Engineering, Hunan University, Changsha, China.

For precision medicine, there is an enormous need to understand the immune evasion mechanism of tumor development, especially when tumor heterogeneity significantly affects the effect of immunotherapy. Recognizing the subtypes of breast cancer based on the immune-related genes helps to understand the immune escape pathways dominated by different subtypes, so as to implement effective treatment measures for different subtypes. For that, we used non-negative matrix factorization and consistent clustering algorithm on The Cancer Genome Atlas RNA-seq breast cancer data and recognized 4 subtypes according to the curated immune-related genes. Then, we conducted differential expression analysis between each subtype of breast cancer and normal tissue of RNA-seq data from non-cancer individuals collected by the Genotype-Tissue Expression to find out subtype-related immune genes. After that, we carried out correlation analysis between copy number variants (CNV) and mRNA of immune genes and investigated the regulatory mechanism of the immune genes, which cannot be explained by CNV based on ATAC-seq data. The experimental results reveal that and are potential for immune evasion in all 4 subgroups. The expression variations of can be mainly explained by its CNV, while the expression variation of is more likely regulated by transcript factors.
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http://dx.doi.org/10.3389/fgene.2020.595324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693564PMC
November 2020

Braking process identification of high-speed trains for automatic train stop control.

ISA Trans 2021 May 2;111:171-179. Epub 2020 Nov 2.

School of Internet of Things Engineering, Jiangnan University, China.

Automatic train stop control (ATSC) is a key function of the automatic train operation (ATO) system. An accurate braking process model can help to improve the control strategy. In this paper, the braking process for stop control of high-speed trains is formulated as a single-point time delay model, based on the principle of practical braking processes. Furthermore, a Picard iteration based identification method is first applied to the time delay system, and a train braking process identification method is proposed. The method is straightforward, and the parameters can be identified based on the principle of ordinary differential equations. The effectiveness of the braking process model and the identification method is illustrated by real-life experimental data.
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http://dx.doi.org/10.1016/j.isatra.2020.10.059DOI Listing
May 2021

Cardiac contractility modulation attenuates structural and electrical remodeling in a chronic heart failure rabbit model.

J Int Med Res 2020 Oct;48(10):300060520962910

Department of Cardiology, Hebei General Hospital, Shijiazhuang, Hebei Province, People's Republic of China.

Background: Cardiac contractility modulation (CCM) is non-excitatory electrical stimulation for improving cardiac function. This study aimed to evaluate the effects of CCM on structural and electrical remodeling in a rabbit model of chronic heart failure (CHF).

Methods: Thirty rabbits were randomly divided into the sham, CHF, and CCM groups. The CHF model was induced 12 weeks after trans-aortic constriction by pressure unloading and CCM was delivered to the myocardium for 4 weeks. Corrected QT intervals, the ventricular effective refractory period, and inducibility of ventricular tachycardia were measured by an electrophysiological examination. Connective tissue growth factor, galectin-3, Kv4.3, KCNQ1, KCNH2, and connexin 43 protein levels were measured by western blotting.

Results: The CHF group had a significantly prolonged corrected QT interval and ventricular effective refractory period, and increased inducibility of ventricular tachycardia. Prominent myocardial fibrosis and increased hydroxyproline content were observed in the CHF group, but these were suppressed in the CCM group. Kv4.3, KCNQ1, KCNH2, and connexin 43 protein levels were significantly lower in the CHF group, but treatment with CCM partially restored their levels.

Conclusions: CCM attenuates myocardial structural and electrical remodeling during CHF. These findings provide evidence for clinical use of CCM in treating CHF.
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http://dx.doi.org/10.1177/0300060520962910DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7556184PMC
October 2020

Ultrasound imaging of carotid web with atherosclerosis plaque: a case report.

J Med Case Rep 2020 Sep 8;14(1):145. Epub 2020 Sep 8.

Department of Ultrasound, Beijing Tiantan Hospital, Capital Medical University, No. 119, 4th South Ring West Road, Fengtai District, Beijing, 100070, China.

Background: To the best of our knowledge, no previous studies on carotid webs with atherosclerosis plaque have been conducted. Thus, both radiologists and clinicians have insufficient knowledge of this disease, which could lead to misdiagnosis and missed diagnosis. An accurate diagnosis is beneficial to clinical management and prevention of stroke. Here, we present a case of a carotid web with an atherosclerotic plaque, which was confirmed by histopathology and was treated at the Department of Neurosurgery, Beijing Tiantan Hospital.

Case Presentation: We report a rare case of a carotid web with an atherosclerotic plaque in a 61-year-old Han man. He presented to our hospital with history of intermittent dizziness and slurred speech for 1.5 years and numbness of both upper limbs for 4 months. A computed tomography angiography examination indicated severe stenosis at the beginning of the left internal carotid artery with plaque surface ulceration. Doppler ultrasound examination showed a carotid web with a thin isoechoic plaque and a membrane-like structure protruding into the lumen from the lateral posterior wall at the beginning of the left internal carotid artery. The thin isoechoic plaque could be seen at the base of the membrane-like structure. Carotid endarterectomy was performed to alleviate symptoms. A carotid web with atherosclerosis was diagnosed intraoperatively, and postoperative pathology confirmed extensive intima fibroid hyperplasia accompanied with myxoid degeneration. The base of the carotid web was attached to the thin atherosclerosis plaque, and between the web and the plaque, a cavity was observed. In this case report, we aim to discuss the diagnosis of carotid web with atherosclerosis, its physiopathology and management, and the possible reasons for missed diagnosis or misdiagnosis.

Conclusion: Carotid webs with atherosclerosis have no known etiological factors and are rarely reported. Thus, carotid webs could be easily confused with ulcerations on the surface of the atherosclerosis plaque. The diagnosis could be difficult and effective management remains indeterminate. Moreover, prompt recognition of this disease is key to correct treatment and management. Hence, this case report and the relevant data in the literature could contribute to the improvement of the diagnosis and treatment of this disease.
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http://dx.doi.org/10.1186/s13256-020-02446-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7487535PMC
September 2020

Reactive Astrogliosis: Implications in Spinal Cord Injury Progression and Therapy.

Oxid Med Cell Longev 2020 19;2020:9494352. Epub 2020 Aug 19.

Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, No. 105, Jiefang Road, Jinan, Shandong 250013, China.

Astrocytes are the most populous glial cells in the central nervous system (CNS). They are essential to CNS physiology and play important roles in the maintenance of homeostasis, development of synaptic plasticity, and neuroprotection. Nevertheless, under the influence of certain factors, astrocytes may also exert detrimental effects through a process of reactive astrogliosis. Previous studies have shown that astrocytes have more than one type of polarization. Two types have been extensively researched. One is a damaging change that occurs under inflammation and has been termed A1 astrocyte, while the other is a restorative change that occurs under ischemic induction and was termed A2 astrocyte. Researchers are now increasingly paying attention to the role of astrocytes in spinal cord injury (SCI), degenerative diseases, chronic pain, neurological tumors, and other CNS disorders. In this review, we discuss (a) the characteristics of polarized astrocytes, (b) the relationship between astrocyte polarization and SCI, and (c) new implications of reactive astrogliosis for future SCI therapies.
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http://dx.doi.org/10.1155/2020/9494352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455824PMC
May 2021

The correlation between calcification in carotid plaque and stroke: calcification may be a risk factor for stroke.

Int J Clin Exp Pathol 2019 1;12(3):750-758. Epub 2019 Mar 1.

Department of Ultrasound, Beijing Tiantan Hospital, Capital Medical University Beijing, China.

Background: There are few studies on the relationship between calcified plaques and stroke by ultrasound. We investigated the association between calcification in carotid plaque and stroke by analyzing the different characteristics of calcification and neovascularization distribution in heterogeneous plaques by both two-dimensional and contrast-enhanced ultrasound (CEUS).

Methods: A total of 69 patients who were about to undergo carotid endarterectomy were selected between January 2016 and December 2017. Thirty-eight patients with cerebral ischemia were placed in the symptomatic group (amaurosis, TIA and no disability in the previous 6 months), and the other 31 patients, who were asymptomatic, were placed in the asymptomatic group. Two-dimensional ultrasound and CEUS were used to detect the calcification distribution characteristics and neovascularization in the plaques of all subjects. The differences of the calcification location, shape, quantity, and enhancement in the plaques were compared between the two groups.

Results: There was no significant difference in calcification location between the two groups (P > 0.05). The symptomatic group had more nodular calcification but less strip calcification compared with the asymptomatic group (both P < 0.05). There was no significant difference in mixed morphologic calcification between the two groups (P > 0.05). The symptomatic group had a higher calcification quantity (P < 0.05). The symptomatic group exhibited more fibrous cap fracture and intra-plaque hemorrhage in H&E staining (χ = 17.133, < 0.001, = 10.003, = 0.003) and higher CD31 expression ( = 7.584, = 0.000).

Conclusions: The quantity and shape of the calcification, and the presence of neovascularization adjacent to the calcification have certain effects on the stability of plaques. Multiple calcifications, nodular calcification, and neovascularization near calcification may cause plaque rupture and therefore might be risk factors for stroke. Our results suggest that the joint use of two-dimensional ultrasound and CEUS can provide comprehensive information on plaques to assess their stability.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6945186PMC
March 2019

Comparative proteomes change and possible role in different pathways of microRNA-21a-5p in a mouse model of spinal cord injury.

Neural Regen Res 2020 Jun;15(6):1102-1110

Department of Spinal Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong Province, China.

Our previous study found that microRNA-21a-5p (miR-21a-5p) knockdown could improve the recovery of motor function after spinal cord injury in a mouse model, but the precise molecular mechanism remains poorly understood. In this study, a modified Allen's weight drop was used to establish a mouse model of spinal cord injury. A proteomics approach was used to understand the role of differential protein expression with miR-21a-5p knockdown, using a mouse model of spinal cord injury without gene knockout as a negative control group. We found that after introducing miR-21a-5p knockdown, proteins that played an essential role in the regulation of inflammatory processes, cell protection against oxidative stress, cell redox homeostasis, and cell maintenance were upregulated compared with the negative control group. Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis identified enriched pathways in both groups, such as the oxidative phosphorylation pathway, which is relevant to Parkinson's disease, Huntington's disease, Alzheimer's disease, and cardiac muscle contraction. We also found that miR-21a-5p could be a potential biomarker for amyotrophic lateral sclerosis, as miR-21a-5p becomes deregulated in this pathway. These results indicate successful detection of some important proteins that play potential roles in spinal cord injury. Elucidating the relationship between these proteins and the recovery of spinal cord injury will provide a reference for future research of spinal cord injury biomarkers. All experimental procedures and protocols were approved by the Experimental Animal Ethics Committee of Shandong University of China on March 5, 2014.
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http://dx.doi.org/10.4103/1673-5374.270418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034281PMC
June 2020

Reorganization of the brain in spinal cord injury: a meta-analysis of functional MRI studies.

Neuroradiology 2019 Nov 16;61(11):1309-1318. Epub 2019 Aug 16.

Department of Orthopedics, Shandong First Medical University/ West China Hospital, Sichuan University, Chengdu, Shandong/Sichuan, China.

Purpose: Reorganization of the brain is considered the key mechanism of functional recovery in patients after spinal cord injury (SCI). This meta-analysis assessed abnormal brain activation in SCI patients to understand the pattern of reorganization in the brain after SCI.

Methods: Functional magnetic resonance imaging (fMRI) studies that compared SCI patients with controls and were published before August 30, 2018, were extracted from the PubMed, Web of Science, and EMBASE databases. Voxel-wise whole-brain meta-analysis and region-of-interest meta-analysis of group differences were separately performed. Then, meta-regression analysis was conducted with several clinical characteristics as regressors.

Results: Sixteen studies that met the inclusion criteria were identified. Compared with control individuals, SCI patients showed increased activation in the sensorimotor cortex in both whole-brain and region-of-interest (ROI) analyses. In addition, whole-brain meta-analysis revealed increased activation in the cerebellum, and this increase was positively correlated with lesion level and injury severity.

Conclusion: Our results demonstrated that reorganization occurred mainly in the sensorimotor system of the brain after SCI, implying that brain functions involved in sensorimotor demands can still be preserved in this condition. These findings provide opportunities for future studies in terms of therapeutic strategies and prognosis assessment.
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http://dx.doi.org/10.1007/s00234-019-02272-3DOI Listing
November 2019

Downregulation of can enhance the radiosensitivity of osteosarcoma and .

Epigenomics 2019 08 29;11(11):1283-1305. Epub 2019 Jul 29.

Department of Pediatrics, Qilu Hospital, Shandong University, Jinan, China.

To investigate the effect of gene on radiotherapy for osteosarcoma. Gene Expression Omnibus database, RT-qPCR and immunohistochemical analysis were performed. Cell proliferation and cell cycle experiments were conducted after knockdown of . Cell scratch, reactive oxygen species production and apoptosis experiments were conducted after the combination of radiotherapy and silencing. Then the xenograft mode was further conducted. was highly expressed in human osteosarcoma. Suppression of inhibited osteosarcoma cell proliferation and induced cell cycle arrest at the G2/M phase. Downregulation of combined with radiation can substantially inhibit clonal formation and migration, and promote apoptosis of osteosarcoma cells and . downregulation can enhance the radiosensitivity of osteosarcoma and .
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http://dx.doi.org/10.2217/epi-2019-0125DOI Listing
August 2019

Silencing miR-21 induces polarization of astrocytes to the A2 phenotype and improves the formation of synapses by targeting glypican 6 the signal transducer and activator of transcription-3 pathway after acute ischemic spinal cord injury.

FASEB J 2019 10 2;33(10):10859-10871. Epub 2019 Jul 2.

Jinan Central Hospital, Shandong University, Jinan, China.

Ischemic spinal cord injury (ISCI) results in the motor sensory dysfunction of the limbs below the injury site. In response to the injury, astrocytes develop into neuroprotective astrocytes [(neurotrophic reactive astrocytes (A2s)] to mitigate the damage. MicroRNA (miR)-21 can promote the development of neuroinflammation in previous studies. Our aim was to investigate the effect of miR-21 on its polarization. We used the abdominal aortic occlusion model . Immunohistochemistry was used to detect the distribution of A2s in the spinal cord. We used an oxygen glucose deprivation method to model astrocytes ischemia and tested proliferation, migration, and excitability of A2s using an 5-ethynyl -2'-deoxyuridine kit, wound scratch assay, and calcium-ion probe. After adjustment, we detected the model and target genes of A2s using PCR, Western blot, immunofluorescence, and chromatin immunoprecipitation. We demonstrated that naive astrocytes were transformed into A2s by ischemia. And miR-21, which can regulate the signal transducer and activator of transcription-3 pathway, can transform neurotoxic reactive astrocyte into A2. Moreover, we also verified the mechanism of A2s promoting synaptic formation and nerve growth. miR-21 is a switch to regulate the polarization of reactive astrocyte, and it promoted synapsis formation and nerites growth after acute ISCI.-Su, Y., Chen, Z., Du, H., Liu, R., Wang, W., Li, H., Ning, B. Silencing miR-21 induces polarization of astrocytes to the A2 phenotype and improves the formation of synapses by targeting glypican 6 the signal transducer and activator of transcription-3 pathway after acute ischemic spinal cord injury.
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http://dx.doi.org/10.1096/fj.201900743RDOI Listing
October 2019

The association between body mass index and in-hospital outcome among patients with acute myocardial infarction-Insights from China Acute Myocardial Infarction (CAMI) registry.

Nutr Metab Cardiovasc Dis 2019 08 11;29(8):808-814. Epub 2019 Apr 11.

Fuwai Hospital Chinese Academy of Medical Sciences & Peking Union Medical College, National Center for Cardiovascular Diseases, State Key Laboratory of Cardiovascular Disease, China. Electronic address:

Background: The relationship between body mass index (BMI) and in-hospital mortality risk among patients with acute myocardial infarction (AMI) remains controversial.

Methods And Results: We included 35,964 patients diagnosed with AMI in China Acute Myocardial Infarction registry between January 2013 and December 2016. Patients were categorized into 4 groups according to BMI level: BMI <18.5, 18.5-24.9, 25-30, and ≥30 kg/m for underweight, normal, overweight, and obese groups, respectively. Clinical data were extracted for each patient, and multivariable logistic regression analysis was used to examine the association between BMI level and in-hospital mortality. Compared with normal-weight patients, obese patients were younger, more often current smokers, and more likely to have hypertension, hyperlipidemia, and diabetes. Multivariable regression analysis results demonstrated that compared with normal group, underweight group had significantly higher in-hospital mortality (odds ratio [OR]: 1.34; 95% confidence interval [CI]: 1.06-1.69; p = 0.016), while overweight group (OR: 0.86; 95% CI: 0.77-0.97; p = 0.011) and obese group (OR: 0.65; 95% CI: 0.46-0.91; p = 0.013) had lower mortality. All subgroups showed a trend toward lower in-hospital mortality risk as BMI increased.

Conclusions: Our study provided robust evidence supporting "obesity paradox" in a contemporary large-scale cohort of patients with AMI and demonstrated that increased BMI was independently associated with lower in-hospital mortality.
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http://dx.doi.org/10.1016/j.numecd.2019.04.001DOI Listing
August 2019

Identification of noncoding RNA expression profiles and regulatory interaction networks following traumatic spinal cord injury by sequence analysis.

Aging (Albany NY) 2019 04;11(8):2352-2368

Jinan Central Hospital Affiliated to Shandong University, Jinan, China.

Aim: To systematically profile and characterize the noncoding RNA (ncRNA) expression pattern in the lesion epicenter of spinal tissues after traumatic spinal cord injury (TSCI) and predicted the structure and potential functions of the regulatory networks associated with these differentially expressed ncRNAs and mRNAs.

Results: A total of 498 circRNAs, 458 lncRNAs, 155 miRNAs and 1203 mRNAs were identified in TSCI mice models to be differentially expressed. The regulatory networks associated with these differentially expressed ncRNAs and mRNAs were constructed.

Materials And Methods: We used RNA-Seq, Gene ontology (GO), KEGG pathway analysis and co-expression network analyses to profle the expression and regulation patterns of noncoding RNAs and mRNAs of mice models after TSCI. The findings were validated by quantitative real-time PCR (qRT-PCR) and Luciferase assay.

Conclusion: noncoding RNAs might play important roles via the competing endogenous RNA regulation pattern after TSCI, further findings arising from this study will not only expand the understanding of potential ncRNA biomarkers but also help guide therapeutic strategies for TSCI.
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http://dx.doi.org/10.18632/aging.101919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520015PMC
April 2019

Specific Brain Morphometric Changes in Spinal Cord Injury: A Voxel-Based Meta-Analysis of White and Gray Matter Volume.

J Neurotrauma 2019 08 23;36(15):2348-2357. Epub 2019 Apr 23.

1Department of Orthopedic Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, China.

The objective of the study was to investigate degenerative changes of white matter volume (WMV) and gray matter volume (GMV) in individuals after a spinal cord injury (SCI). Published studies of whole-brain voxel-based morphometry (VBM) published between January 1, 2006 and March 1, 2018 comparing SCI patients with controls were collected by searching PubMed, Web of Science, and EMBASE databases. Voxel-wise meta-analyses of GMV and WMV differences between SCI patients and controls were performed separately using seed-based d mapping. Twelve studies with 12 GMV data sets and 9 WMV data sets yielded a total of 466 individuals (190 SCI patients and 276 controls) who were included in this meta-analysis. Compared with controls, SCI patients showed GMV atrophy in sensorimotor system regions including the bilateral sensorimotor cortex (S1 and M1), the supplementary motor area (SMA), paracentral gyrus, thalamus, and basal ganglia, as well as WMV loss in the corticospinal tract.GMV aberrancies were also demonstrated in brain regions responsible for cognition and emotion, such as the orbitofrontal cortex (OFC) and the left insula. Additionally, GMV in both the bilateral S1 and the left SMA was positively correlated with the time span after the injury. In conclusion, anatomical atrophy in cortical-thalamic-spinal pathways suggested that SCIs may result in degenerative changes of the sensorimotor system. Further, OFC and insula GMV abnormalities may explain symptoms such as neuropathic pain and potential cognitive-emotional impairments in chronic SCI patients. These findings indicate that anatomical brain magnetic resonance imaging (MRI) protocols could be neuroimaging biomarkers for interventional studies and treatments.
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http://dx.doi.org/10.1089/neu.2018.6205DOI Listing
August 2019

Patient satisfaction of radiofrequency ablation for symptomatic benign solid thyroid nodules: our experience for 2-year follow up.

BMC Cancer 2019 Feb 13;19(1):147. Epub 2019 Feb 13.

Department of Ultrasound, Beijing Tian Tan Hospital, Capital Medical University, No. 119 West Road of South 4th Ring Road, Fengtai District, Beijing, 100160, China.

Background: The patient satisfaction of symptoms improvement and disease factors that may affect long-term treatment efficacy of radiofrequency ablation (RFA) for non-functioning solid benign thyroid nodules (TNs) over a 2-year follow up study was investigated.

Methods: This retrospective study evaluated 194 non-functioning solid benign TNs of 103 patients. The TNs were categorized as small (≤5 ml), medium (5.1 to 13 ml), intermediate (13.1 to 30 ml) and large (over 30 ml) according to the initial volume of TNs before ablation. Clinical evaluation and contrast-enhanced ultrasound (CEUS) were carried out before ablation and the follow up at 1, 3, 6 months and every 6 months after ablation. All patients were asked to assess the cosmetic score (1-4 scores) and symptom score (0-10 scores) before ablation and every follow up after ablation.

Results: All patients underwent RFA without any major complications. The mean treatment sessions were 1.5 ± 0.6. 98 nodules required a single session (98/194, 50.5%), 87 required two sessions (87/194, 44.9%), 9 required three sessions (9/194, 4.6%). The average follow up months were 16.3 ± 5.6 (range, 6-24 months) and no nodule regrew in our study. After RFA treatment, the TNs volume significantly decreased (P < 0.001). The small group of nodules shrunk larger compared to the medium, intermediate and large groups (P < 0.001). Cosmetic signs and pressure symptoms were significantly improved, particularly in the intermediate and large groups (P < 0.05).

Conclusions: RFA is effective for treating non-functioning solid benign TNs and controlling clinical symptoms with a low complication rate during 2 years follow up. The reduction rate was related to the initial volume of nodules. Patients were satisfied with cosmetic signs and pressure symptoms improvement, particularly in the intermediate and large groups. However, multiple RFA treatments should be used in larger nodules to achieve the desired clinical outcomes.
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http://dx.doi.org/10.1186/s12885-019-5338-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6375217PMC
February 2019

Parallel Intelligent Systems for Integrated High-Speed Railway Operation Control and Dynamic Scheduling.

IEEE Trans Cybern 2018 Dec 17;48(12):3381-3389. Epub 2018 Jul 17.

The information exchange gap between current operation control and dynamic scheduling in high-speed railway systems (HRSs) still exists, and this gap has hindered the further integrative improvement of HRSs. This paper aims to explore a feasible solution to bridging the information exchange gap for further improving the efficiency of HRSs, with the parallel intelligent systems for integrated HRS operation control and dynamic scheduling first analyzed and constructed using the ACP approach, that is, "artificial systems" (A), "computational experiments," (C) and "parallel execution" (P). Then, on the basis of the constructed parallel intelligent systems, experiments on several typical scenarios in HRSs are conducted to achieve a set of control and management strategies for actual HRSs. Experimental results show that a number of powerful tools provided by the proposed parallel intelligent systems can be utilized not only to study the current HRSs, but also to further undertake research on integrated operation control and dynamic scheduling for HRSs.
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http://dx.doi.org/10.1109/TCYB.2018.2852772DOI Listing
December 2018

microRNA-21 regulates astrocytic reaction post-acute phase of spinal cord injury through modulating TGF-β signaling.

Aging (Albany NY) 2018 Jun;10(6):1474-1488

Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, China.

Astrogliosis following spinal cord injury (SCI) was considered as a negative factor for neural regeneration. We found that miR-21 was significantly upregulated after SCI. So, we aim to determine whether miR-21 acts in a positive manner post SCI. , we measured the proliferation, apoptosis and cytokine secretion of primary cultured astrocytes after modulating the expression of miR-21 by western blot, RT-PCR and immunofluorescence. , we performed a modified Allen's weight drop model. Manipulation of the miR-21 expression level was achieved by interfering with antagomir and agomir. Clinic score was evaluated and recorded every day. Then, western blot, immunohistochemistry, TUNEL assay and ELISA were performed to detect pathological and functional alterations. Our results demonstrate that miR-21 can modulate the secretion, proliferation and apoptosis of astrocytes to promote recovery after SCI both and . These effects are likely mediated through transforming growth factor beta mediated targeting of the PI3K/Akt/mTOR pathway. These data suggest that miR-21 can regulate astrocytic function, then promote the functional recovery after SCI. We therefore highlight the positive effects of miR-21 after SCI.
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http://dx.doi.org/10.18632/aging.101484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6046223PMC
June 2018

Knockdown of MicroRNA-21 Promotes Neurological Recovery After Acute Spinal Cord Injury.

Neurochem Res 2018 Aug 22;43(8):1641-1649. Epub 2018 Jun 22.

Department Spinal Surgery, Jinan Central Hospital Affiliated to Shandong University, 105 Jiefang Road, Jinan, 250013, Shandong, China.

To assess the therapeutic effects of microRNA-21 (miR-21) knockdown (KD) for acute thoracic spinal cord contusion using a mouse model. Forty C57/BL6 mice were randomly divided into four groups: mice in the sham-operated (Sham) group received surgical procedure without spinal cord contusion; the spinal cord injury (SCI) group mice underwent spinal cord contusion without treatment; mice in the miR-21 KD group underwent spinal cord contusion followed by a single dose subdural injection of miR-21 KD vectors (1 × 10 TU); and the negative control (NC) group mice were given subdural injection of comparable amount of NC vectors (1 × 10 TU) after spinal cord contusion. The Basso Mouse Scale (BMS) was employed to assess hindlimb motor functions. Hematoxylin-eosin and Luxol fast blue staining were performed to evaluate pathologic changes in spinal cord tissues. Peripheral blood serum levels of tumor necrosis factor α (TNFα), transforming growth factor β (TGF-β) and interleukin-1β (IL-1β) were determined by the enzyme-linked immunosorbent assay, and mRNA expression of Brain derived neurotrophic factor (BDNF) was examined by reverse transcription-polymerase chain reaction (RT-PCR). Western blotting was performed to analyze the AKT signaling pathway. KD of miRNA-21 effectively improved the BMS scores at day 14 post-surgery compared with the SCI group (p < 0.01). The spinal cord tissue in the miR-21 KD group displayed the most overt histologic signs of recovery, with axonal regeneration and the recovery of neuronal morphology at day 14 post-surgery. Significantly alleviation of TGF-β1, TNF-α and IL-1β was also found in sera from the miR-21 inhibition group in comparison to others, whereas BDNF gene expression was upregulated following miR-21 KD (p < 0.01). Further, significantly decreased AKT phosphorylation activity was illustrated in the miR-21 KD group (p < 0.001). The data suggest that miR-21 KD significantly reduces the inflammatory response at the damaged spinal cord site and promotes motor functional recovery. The treatment also elevated expression of BDNF, a neurotrophin participating in nerve regeneration.
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http://dx.doi.org/10.1007/s11064-018-2580-1DOI Listing
August 2018

MicroRNA-21a-5p promotes fibrosis in spinal fibroblasts after mechanical trauma.

Exp Cell Res 2018 09 5;370(1):24-30. Epub 2018 Jun 5.

Department of Spinal Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong, China. Electronic address:

Traumatic spinal cord injury (SCI) causes permanent disability to at least 180,000 people per year worldwide. Early regulation of spinal fibroblast proliferation may inhibit fibrotic scar formation, allowing the creation of a favorable environment for neuronal regeneration and thereby enhancing recovery from traumatic SCIs. In this study, we aimed to identify the role of microRNA-21a-5p (miR-21a-5p) in regulating spinal fibroblasts after mechanical trauma and to investigate the dysregulation of miR-21a-5p in the pathological process of spinal SCI. We investigated the differential expression of microRNAs in primary spinal fibroblasts after mechanical trauma and found that the expression of miR-21a-5p was higher in spinal fibroblasts after scratch damage (SD). In addition, mouse spinal fibroblasts were transfected with miR-21a-5p mimics/inhibitor, and the role of miR-21a-5p in spinal fibrogenic activation was analyzed. These experiments demonstrated that miR-21a-5p overexpression promoted fibrogenic activity in spinal fibroblasts after mechanical trauma, as well as enhancing proliferation and attenuating apoptosis in spinal fibroblasts. Finally, the potential role of miR-21a-5p in regulating the Smad signaling pathway was examined. MiR-21a-5p activated the Smad signaling pathway by enhancing Smad2/3 phosphorylation. These results suggest that miR-21a-5p promotes spinal fibrosis after mechanical trauma. Based on these findings, we propose a close relationship between miR-21a-5p and spinal fibrosis, providing a new potential therapeutic target for SCI.
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http://dx.doi.org/10.1016/j.yexcr.2018.06.002DOI Listing
September 2018

Combination of anginex gene therapy and radiation decelerates the growth and pulmonary metastasis of human osteosarcoma xenografts.

Cancer Med 2018 06 16;7(6):2518-2529. Epub 2018 Apr 16.

Jinan Central Hospital Affiliated to Shandong University, No. 105, Jiefang Road, Jinan, 250013, Shandong, China.

Investigate whether rAAV-anginex gene therapy combined with radiotherapy could decrease growth and pulmonary metastasis of osteosarcoma in mice and examine the mechanisms involved in this therapeutic strategy. During in vitro experiment, multiple treatment regimes (rAAV-eGFP, radiotherapy, rAAV-anginex, combination therapy) were applied to determine effects on proliferation of endothelial cells (ECs) and G-292 osteosarcoma cells. During in vivo analysis, the same multiple treatment regimes were applied to osteosarcoma tumor-bearing mice. Use microcomputed tomography to evaluate tumor size. Eight weeks after tumor cell inoculation, immunohistochemistry was used to assess the therapeutic efficacy according to microvessel density (MVD), proliferating cell nuclear antigen (PCNA), and terminal-deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assays. Metastasis of lungs was also evaluated by measuring number of metastatic nodules and wet weight of metastases. The proliferation of ECs and the tumor volumes in combination therapy group were inhibited more effectively than the other three groups at end point (P < 0.05). Cell clone assay showed anginex had radiosensitization effect on ECs. Immunohistochemistry showed tumors from mice treated with combination therapy exhibited the lowest MVD and proliferation rate, with highest apoptosis rate, as confirmed by IHC staining for CD34 and PCNA and TUNEL assays (P < 0.05). Combination therapy also induced the fewest metastatic nodules and lowest wet weights of the lungs (P < 0.05). rAAV-anginex combined with radiotherapy induced apoptosis of osteosarcoma cells and inhibited tumor growth and pulmonary metastasis on the experimental osteosarcoma models. We conclude that the primary mechanism of this process may be due to sensitizing effect of anginex to radiotherapy.
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http://dx.doi.org/10.1002/cam4.1476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010866PMC
June 2018

MicroRNA-21-5p mediates TGF-β-regulated fibrogenic activation of spinal fibroblasts and the formation of fibrotic scars after spinal cord injury.

Int J Biol Sci 2018 15;14(2):178-188. Epub 2018 Jan 15.

Jinan Central Hospital Affiliated to Shandong University, No. 105, Jiefang Road, Jinan, Shandong, 250013, China.

Little regeneration of transected axons occurs after the damage caused by traumatic spinal cord injury (SCI), and unidirectional and irreversible fibrotic scars are thought to be the main chemical and physical obstacle for axonal regrowth in SCI pathology. We previously demonstrated that microRNA (miR)-21-5p and transforming growth factor (TGF)-β1, a central pathological mediator of fibrotic diseases, were significantly up-regulated in the lesion epicenter after SCI. Here, we found that TGF-β1 enhanced miR-21-5p expression in primary spinal fibroblasts, and regulated the expression of fibrosis-related genes. The overexpression of miR-21-5p promoted the pro-fibrogenic activity of TGF-β1 in spinal fibroblasts, while miR-21-5p knockdown attenuated this activity. We identified Smad7 as a target gene of miR-21-5p, suggesting a potential mechanism for the role of miR-21-5p in spinal fibrosis through regulating Smad7 expression. Furthermore, miR-21-5p knockdown in a mouse model significantly improved motor functional recovery after spinal cord injury. These data demonstrate that miR-21-5p functions in an amplifying circuit to enhance TGF-β signaling events in the activation of spinal fibroblasts and suggest that miR-21-5p is a potential therapeutic target in the treatment of fibrotic scar formation after SCI.
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http://dx.doi.org/10.7150/ijbs.24074DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5821039PMC
April 2019

Robust fault detection for the dynamics of high-speed train with multi-source finite frequency interference.

ISA Trans 2018 Apr 15;75:76-87. Epub 2018 Feb 15.

State Key Laboratory of Rail Traffic Control and Safety, Beijing Jiaotong University, Beijing Haidian, 100044, China. Electronic address:

This paper proposes a composite fault detection scheme for the dynamics of high-speed train (HST), using an unknown input observer-like (UIO-like) fault detection filter, in the presence of wind gust and operating noises which are modeled as disturbance generated by exogenous system and unknown multi-source disturbance within finite frequency domain. Using system input and system output measurements, the fault detection filter is designed to generate the needed residual signals. In order to decouple disturbance from residual signals without truncating the influence of faults, this paper proposes a method to partition the disturbance into two parts. One subset of the disturbance does not appear in residual dynamics, and the influence of the other subset is constrained by H performance index in a finite frequency domain. A set of detection subspaces are defined, and every different fault is assigned to its own detection subspace to guarantee the residual signals are diagonally affected promptly by the faults. Simulations are conducted to demonstrate the effectiveness and merits of the proposed method.
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http://dx.doi.org/10.1016/j.isatra.2018.01.032DOI Listing
April 2018

Neuroprotective mechanisms of rutin for spinal cord injury through anti-oxidation and anti-inflammation and inhibition of p38 mitogen activated protein kinase pathway.

Neural Regen Res 2018 Jan;13(1):128-134

Department of Spinal Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong Province, China.

Rutin has anti-inflammatory, antioxidant, anti-viral, anti-tumor and immune regulatory effects. However, the neuroprotective effects of rutin in spinal cord injury are unknown. The p38 mitogen activated protein kinase (p38 MAPK) pathway is the most important member of the MAPK family that controls inflammation. We assumed that the mechanism of rutin in the repair of spinal cord injury is associated with the inhibition of p38 MAPK pathway. Allen's method was used to establish a rat model of spinal cord injury. The rat model was intraperitoneally injected with rutin (30 mg/kg) for 3 days. After treatment with rutin, Basso, Beattie and Bresnahan locomotor function scores increased. Water content, tumor necrosis factor alpha, interleukin 1 beta, and interleukin 6 levels, p38 MAPK protein expression and caspase-3 and -9 activities in T spinal cord decreased. Oxidative stress related markers superoxide dismutase and glutathione peroxidase levels increased in peripheral blood. Rutin exerts neuroprotective effect through anti-oxidation, anti-inflammation, anti-apoptosis and inhibition of p38 MAPK pathway.
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http://dx.doi.org/10.4103/1673-5374.217349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5840978PMC
January 2018

Rapamycin prevents the intervertebral disc degeneration via inhibiting differentiation and senescence of annulus fibrosus cells.

Aging (Albany NY) 2018 01;10(1):131-143

Department of Orthopedic Surgery, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P. R. China.

The effects of bleomycin and rapamycin on cellular senescence and differentiation of rabbit annulus fibrosus stem cells (AFSCs) were investigated using a cell culture model. The results showed that bleomycin induced cellular senescence in AFSCs as evidenced by senescence-associated secretory phenotype. The morphology of AFSCs was changed from cobblestone-like cells to pancake-like cells. The senescence-associated β-galactosidase activity, the protein expression of P16 and P21, and inflammatory-related marker gene levels IL-1β, IL-6, and TNF-α were increased in bleomycin-treated AFSCs in a dose-dependent manner. Rapamycin treatment decreased the gene expression of MMP-3, MMP-13, IL-1β, IL-6, TNF-α, and protein levels of P16 and P21 in bleomycin-treated AFSCs. Furthermore, neither bleomycin nor rapamycin changed the ribosomal S6 protein level in AFSCs. However, the phosphorylation of the ribosomal S6 protein was increased in bleomycin-treated AFSCs and decreased in rapamycin-treated AFSCs. AFSCs differentiated into adipocytes, osteocytes, and chondrocytes when they were cultured with respective differentiation media. Rapamycin inhibited multi-differentiation potential of AFSCs in a concentration-dependent manner. Our findings demonstrated that mammalian target of rapamycin (mTOR) signaling affects cellular senescence, catabolic and inflammatory responses, and multi-differentiation potential, suggesting that potential treatment value of rapamycin for disc degenerative diseases, especially lower back pain.
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http://dx.doi.org/10.18632/aging.101364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811247PMC
January 2018

Corrigendum to "Intraoperative Contrast Enhanced Ultrasound Evaluates the Grade of Glioma".

Biomed Res Int 2017;2017:5782619. Epub 2017 Jul 18.

Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, 6 Tiantan Xili, Dongcheng District, Beijing 100050, China.

[This corrects the article DOI: 10.1155/2016/2643862.].
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http://dx.doi.org/10.1155/2017/5782619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541787PMC
July 2017