Publications by authors named "Jinhai Wang"

81 Publications

Rapid diagnosis and continuous monitoring of intracerebral hemorrhage with magnetic induction tomography based on stacked autoencoder.

Rev Sci Instrum 2021 Aug;92(8):084707

School of Life Sciences, Tiangong University, 399 Binshui West Street, Xiqing District, Tianjin 300387, People's Republic of China.

Magnetic induction tomography (MIT) is a promising approach in rapid diagnosis and continuous monitoring of cerebral hemorrhage. A new algorithm for the reconstruction of intracerebral hemorrhage with MIT, including the location and volume of hemorrhage, is proposed in this study. First, 2D magnetic resonance imaging and computed tomography images of patients with cerebral hemorrhage were used for the development of simulation models. The Stacked Autoencoder (SAE) network was then used to predict the location and volume of hemorrhage by conductivity reconstruction. Finally, the one-dimensional quantitative monitoring index is proposed as an auxiliary diagnostic indicator for assessment of real-time intracranial electrical characteristics. The 2D simulation results showed that the SAE was able to quickly image the location and volume of the hemorrhages. Compared with the back-projection algorithm, the prediction speed of each frame was improved 15-fold, and the accuracy improved by 90.53%. The extracted one-dimensional quantitative monitoring indicators can describe the bleeding status. The diagnostic accuracy and the imaging speed of cerebral hemorrhage were both improved by constructing a realistic head section model and using the proposed SAE network. This research provides a new alternative for dynamic monitoring of hemorrhages and shows the potential advantages of MIT in noninvasive detection.
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http://dx.doi.org/10.1063/5.0050171DOI Listing
August 2021

Aurora kinase A (AURKA) promotes the progression and imatinib resistance of advanced gastrointestinal stromal tumors.

Cancer Cell Int 2021 Jul 31;21(1):407. Epub 2021 Jul 31.

Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, #88 Jiefang Road, Hangzhou, Zhejiang, People's Republic of China.

Background: Gastrointestinal stromal tumor (GIST) is a common tumor that originates from the alimentary system mesenchyme. Compared to typical gastrointestinal carcinomas, GISTs exhibit unique malignant behaviors. Bioinformatic tools and subsequent experiments were applied to investigate novel targets involved in GIST progression and imatinib resistance.

Methods: Differences in gene expression profiles between advanced and nonadvanced GISTs were comprehensively analyzed based on the Gene Expression Omnibus (GEO) dataset GSE136755. A protein-protein interaction (PPI) network was constructed to identify the potential target gene. Gene set enrichment analysis (GSEA) was used to elucidate relevant biological events related to the target gene based on the GSE47911 dataset. Subsequently, immunohistochemistry and Kaplan-Meier analysis were performed to validate the prognostic value of the target gene in GISTs. Overexpression of the target gene was conducted to analyze its function in the proliferation, apoptosis, and imatinib resistance of GIST/T1 cells.

Results: In the current study, a total of 606 differentially expressed genes (DEGs) were screened based on the GSE136755 dataset, and the upregulated DEGs in advanced GISTs were mainly involved in cell division through functional annotations. The intersecting hub gene, Aurora kinase A (AURKA), was identified by degree and bottleneck algorithms. GSEA revealed that AURKA was involved in cell cycle-related biological processes. Analysis of the Oncomine and GEPIA databases revealed a pattern of elevated AURKA expression in most human malignances. Clinical assays demonstrated that AURKA could be an independent prognostic factor for GISTs. Additionally, overexpression of AURKA was experimentally demonstrated to promote cell proliferation, inhibit cell apoptosis, and enhance imatinib resistance in GIST/T1 cells.

Conclusions: These findings indicated that overexpression of AURKA promoted GIST progression and enhanced imatinib resistance, implying that AURKA is a potential therapeutic target for GISTs.
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http://dx.doi.org/10.1186/s12935-021-02111-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325869PMC
July 2021

A convolutional neural network algorithm for breast tumor detection with magnetic detection electrical impedance tomography.

Rev Sci Instrum 2021 Jun;92(6):064701

School of Life Sciences, Tiangong University, Tianjin 300387, China.

Breast cancer is a malignant tumor disease for which early detection, diagnosis, and treatment are of paramount significance in prolonging the life of patients. Magnetic Detection Electrical Impedance Tomography (MDEIT) based on the Convolutional Neural Network (CNN), which aims to realize non-invasive, high resolution detection of breast tumors, is proposed. First, the MDEIT forward problem of the coronal and horizontal planes of the breast was simulated and solved using the Finite Element Method to obtain sample datasets of different lesions. Then, the CNN was built and trained to predict the conductivity distribution in different orientations of the breast model. Finally, noise and phantom experiments were performed in order to assess the anti-noise performance of the CNN algorithm and its feasibility of detecting breast tumors in practical applications. The simulation results showed that the reconstruction relative error with the CNN algorithm can be reduced to 10%, in comparison with the truncated singular value decomposition algorithm and back propagation algorithm. The CNN algorithm had better stability in the anti-noise performance test. When the noise of 60 dB was added, the shape of the breast tumor could still be restored by the CNN algorithm. The phantom experimental results showed that through the CNN based reconstruction algorithm, the reconstruction conductivity distribution image was legible and the position of the breast tumor could be determined. It is reasonable to conclude that the MDEIT reconstruction method proposed in this study has practical importance for the early and non-invasive detection of breast tumors.
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http://dx.doi.org/10.1063/5.0041423DOI Listing
June 2021

Role of Epoxide Hydrolases and Cytochrome P450s on Metabolism of KZR-616, a First-in-Class Selective Inhibitor of the Immunoproteasome.

Drug Metab Dispos 2021 Sep 7;49(9):810-821. Epub 2021 Jul 7.

Kezar Life Sciences, South San Francisco, California

KZR-616 is an irreversible tripeptide epoxyketone-based selective inhibitor of the human immunoproteasome. Inhibition of the immunoproteasome results in anti-inflammatory activity in vitro and based on promising therapeutic activity in animal models of rheumatoid arthritis and systemic lupus erythematosus KZR-616 is being developed for potential treatment of multiple autoimmune and inflammatory diseases. The presence of a ketoepoxide pharmacophore presents unique challenges in the study of drug metabolism during lead optimization and clinical candidate profiling. This study presents a thorough and systematic in vitro and cell-based enzymatic metabolism and kinetic investigation to identify the major enzymes involved in the metabolism and elimination of KZR-616. Upon exposure to liver microsomes in the absence of NADPH, KZR-616 and its analogs were converted to their inactive diol derivatives with varying degrees of stability. Diol formation was also shown to be the major metabolite in pharmacokinetic studies in monkeys and correlated with in vitro stability results for individual compounds. Further study in intact hepatocytes revealed that KZR-616 metabolism was sensitive to an inhibitor of microsomal epoxide hydrolase (mEH) but not inhibitors of cytochrome P450 (P450) or soluble epoxide hydrolase (sEH). Primary human hepatocytes were determined to be the most robust source of mEH activity for study in vitro. These findings also suggest that the exposure of KZR-616 in vivo is unlikely to be affected by coadministration of inhibitors or inducers of P450 and sEH. SIGNIFICANCE STATEMENT: This work presents a thorough and systematic investigation of metabolism and kinetics of KZR-616 and related analogs in in vitro and cell-based enzymatic systems. Information gained could be useful in assessing novel covalent proteasome inhibitors during lead compound optimization. These studies also demonstrate a robust source in vitro test system that correlated with in vivo pharmacokinetics for KZR-616 and two additional tripeptide epoxyketones.
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http://dx.doi.org/10.1124/dmd.120.000307DOI Listing
September 2021

Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study.

Lancet Oncol 2021 07 15;22(7):977-990. Epub 2021 Jun 15.

Live Surgery Ward, Peking Union Medical College Hospital, Beijing, China.

Background: China has a high burden of hepatocellular carcinoma, and hepatitis B virus (HBV) infection is the main causative factor. Patients with hepatocellular carcinoma have a poor prognosis and a substantial unmet clinical need. The phase 2-3 ORIENT-32 study aimed to assess sintilimab (a PD-1 inhibitor) plus IBI305, a bevacizumab biosimilar, versus sorafenib as a first-line treatment for unresectable HBV-associated hepatocellular carcinoma.

Methods: This randomised, open-label, phase 2-3 study was done at 50 clinical sites in China. Patients aged 18 years or older with histologically or cytologically diagnosed or clinically confirmed unresectable or metastatic hepatocellular carcinoma, no previous systemic treatment, and a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 were eligible for inclusion. In the phase 2 part of the study, patients received intravenous sintilimab (200 mg every 3 weeks) plus intravenous IBI305 (15 mg/kg every 3 weeks). In the phase 3 part, patients were randomly assigned (2:1) to receive either sintilimab plus IBI305 (sintilimab-bevacizumab biosimilar group) or sorafenib (400 mg orally twice daily; sorafenib group), until disease progression or unacceptable toxicity. Randomisation was done using permuted block randomisation, with a block size of six, via an interactive web response system, and stratified by macrovascular invasion or extrahepatic metastasis, baseline α-fetoprotein, and ECOG performance status. The primary endpoint of the phase 2 part of the study was safety, assessed in all patients who received at least one dose of study drug. The co-primary endpoints of the phase 3 part of the study were overall survival and independent radiological review committee (IRRC)-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03794440. The study is closed to new participants and follow-up is ongoing for long-term outcomes.

Findings: Between Feb 11, 2019 and Jan 15, 2020, we enrolled 595 patients: 24 were enrolled directly into the phase 2 safety run-in and 571 were randomly assigned to sintilimab-bevacizumab biosimilar (n=380) or sorafenib (n=191). In the phase 2 part of the trial, 24 patients received at least one dose of the study drug, with an objective response rate of 25·0% (95% CI 9·8-46·7). Based on the preliminary safety and activity data of the phase 2 part, in which grade 3 or worse treatment-related adverse events occurred in seven (29%) of 24 patients, the randomised phase 3 part was started. At data cutoff (Aug 15, 2020), the median follow-up was 10·0 months (IQR 8·5-11·7) in the sintilimab-bevacizumab biosimilar group and 10·0 months (8·4-11·7) in the sorafenib group. Patients in the sintilimab-bevacizumab biosimilar group had a significantly longer IRRC-assessed median progression-free survival (4·6 months [95% CI 4·1-5·7]) than did patients in the sorafenib group (2·8 months [2·7-3·2]; stratified hazard ratio [HR] 0·56, 95% CI 0·46-0·70; p<0·0001). In the first interim analysis of overall survival, sintilimab-bevacizumab biosimilar showed a significantly longer overall survival than did sorafenib (median not reached [95% CI not reached-not reached] vs 10·4 months [8·5-not reached]; HR 0·57, 95% CI 0·43-0·75; p<0·0001). The most common grade 3-4 treatment-emergent adverse events were hypertension (55 [14%] of 380 patients in the sintilimab-bevacizumab biosimilar group vs 11 [6%] of 185 patients in the sorafenib group) and palmar-plantar erythrodysaesthesia syndrome (none vs 22 [12%]). 123 (32%) patients in the sintilimab-bevacizumab biosimilar group and 36 (19%) patients in the sorafenib group had serious adverse events. Treatment-related adverse events that led to death occurred in six (2%) patients in the sintilimab-bevacizumab biosimilar group (one patient with abnormal liver function, one patient with both hepatic failure and gastrointestinal haemorrhage, one patient with interstitial lung disease, one patient with both hepatic faliure and hyperkalemia, one patient with upper gastrointestinal haemorrhage, and one patient with intestinal volvulus) and two (1%) patients in the sorafenib group (one patient with gastrointestinal haemorrhage and one patient with death of unknown cause).

Interpretation: Sintilimab plus IBI305 showed a significant overall survival and progression-free survival benefit versus sorafenib in the first-line setting for Chinese patients with unresectable, HBV-associated hepatocellular carcinoma, with an acceptable safety profile. This combination regimen could provide a novel treatment option for such patients.

Funding: Innovent Biologics.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1470-2045(21)00252-7DOI Listing
July 2021

Subway Gearbox Fault Diagnosis Algorithm Based on Adaptive Spline Impact Suppression.

Entropy (Basel) 2021 May 25;23(6). Epub 2021 May 25.

Beijing Key Laboratory of Performance Guarantee on Urban Rail Transit Vehicles, Beijing University of Civil Engineering and Architecture, Beijing 100044, China.

In the signal processing of real subway vehicles, impacts between wheelsets and rail joint gaps have significant negative effects on the spectrum. This introduces great difficulties for the fault diagnosis of gearboxes. To solve this problem, this paper proposes an adaptive time-domain signal segmentation method that envelopes the original signal using a cubic spline interpolation. The peak values of the rail joint gap impacts are extracted to realize the adaptive segmentation of gearbox fault signals when the vehicle was moving at a uniform speed. A long-time and unsteady signal affected by wheel-rail impacts is segmented into multiple short-term, steady-state signals, which can suppress the high amplitude of the shock response signal. Finally, on this basis, multiple short-term sample signals are analyzed by time- and frequency-domain analyses and compared with the nonfaulty results. The results showed that the method can efficiently suppress the high-amplitude components of subway gearbox vibration signals and effectively extract the characteristics of weak faults due to uniform wear of the gearbox in the time and frequency domains. This provides reference value for the gearbox fault diagnosis in engineering practice.
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http://dx.doi.org/10.3390/e23060660DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8225191PMC
May 2021

Identification of SRGAP2 as a potential oncogene and a prognostic biomarker in hepatocellular carcinoma.

Life Sci 2021 Jul 10;277:119592. Epub 2021 May 10.

Department of Gastroenterology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Shaanxi Key Laboratory of Gastrointestinal Motility Disorders, Xi'an Jiaotong University, Xi'an, Shaanxi, China. Electronic address:

Background: Hepatocellular carcinoma (HCC) is one of the common malignancies worldwide. Slit-Robo GTPase-activating proteins (SRGAPs) have been shown to regulate the occurrence and development of various tumors. However, their specific roles in HCC remain elusive.

Methods: The expression pattern, genetic alteration and prognostic value of SRGAPs in HCC are analyzed by bioinformatics tools. The biological functions of SRGAP2 in HCC cells are demonstrated by in vitro experiments. The high-throughput RNA sequencing is conducted to explore the underlying molecular mechanisms of SRGAP2 in HCC cells.

Results: The expression levels of SRGAP1 and SRGAP2 are significantly elevated in HCC tissues compared to the normal both in Oncomine and TCGA datasets, and SRGAP2 are dramatically upregulated both in mRNA and protein levels. Moreover, higher SRGAP2 is significantly related to the clinical stages of HCC. Meanwhile, SRGAP2 might be an independent prognostic indicator, as it correlates negatively with the clinical outcomes of HCC patients. Further SRGAP2-silencing experiments imply that SRGAP2 might remarkably promote the migration and invasion of HCC cells in an EMT-independent pattern. Based on the high-throughput RNA sequencing of SRGAP2-knockdown HCC cells, enrichment and network analyses demonstrate that SRGAP2 is closely associated with cellular metabolic signaling.

Conclusions: Our study firstly illustrates the crucial role of SRGAP2 in the metastasis of HCC and explores its underlying molecular mechanisms. We identify SRGAP2 as a promising prognostic biomarker and a novel therapeutic target for HCC patients.
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http://dx.doi.org/10.1016/j.lfs.2021.119592DOI Listing
July 2021

Risk factors associated with functional dyspepsia in Chinese children: a cross-sectional study.

BMC Gastroenterol 2021 May 12;21(1):218. Epub 2021 May 12.

Department of Gastroenterology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, China.

Background: There is no study assessing the risk factors associated with functional dyspepsia (FD) in Chinese children based on the Rome IV criteria.

Methods: In this cross-sectional study, we analyzed data from eight representative primary and secondary schools to assess the risk factors associated with FD in Chinese children based on the Rome IV criteria.

Results: A total of 6976 Chinese children were enrolled. The mean age was 14.3 ± 2.5 years, with a range from 7 to 17 years, and 3497 (50.1%) participants were female. FD was prevalent in 209 (3.0%) of the Chinese child population studied. Age (OR = 1.112, P = 0.006), living independent of parents (OR = 1.677, P < 0.001), prolonged school meals (OR = 2.107, P < 0.001), never eat breakfast (OR = 2.192, P = 0.003), often/daily eat cold foods (OR = 2.296, P = 0.002; OR = 2.736, P = 0.011), and often eat pickled foods (OR = 2.390, P = 0.001) were found to be independent risk factors for FD. A nomogram with these risk factors had good discrimination (AUC = 0.727) and calibration (Hosmer-Lemeshow test was 0.851).

Conclusions: Age, living independent of parents, prolonged school meals, never eat breakfast, often/daily eat cold foods and often eat pickled foods were independent risk factors for FD. The nomogram could be used as a quick screening tool to assess FD in Chinese children.
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http://dx.doi.org/10.1186/s12876-021-01800-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114539PMC
May 2021

Enhancement of signal-to-noise ratio for fluorescence endoscope image based on fast digital lock-in algorithm.

R Soc Open Sci 2021 Mar 10;8(3):200779. Epub 2021 Mar 10.

School of Life Sciences, Tiangong University, Tianjin 300387, People's Republic of China.

In this paper, the signal-to-noise ratios (SNR) of two image channels were enhanced with the fast digital lock-in algorithm. In order to simultaneously improve the quality of white and fluorescence images obtained by fluorescence endoscope, and improve the SNR to achieve a better image processing effect, two sources of white light and near-infrared light of a fluorescence endoscope were modulated, then the acquired images were demodulated into white and fluorescence images. A fluorescent endoscope experimental platform was setup to acquire endoscopic images of a target dyed by indocyanine green. The experimental results showed that the SNR of white and fluorescent images without the lock-in algorithm were 36.56 dB and 33.47 dB, respectively. However, with the lock-in algorithm, the SNR of white and fluorescent images were 39.54 dB and 35.70 dB, respectively. The SNR of white and fluorescent images was increased by 8.2% and 6.7%, respectively, by appling the digital lock-in algorithm. Therefore, this novel fluorescence endoscope based on the fast digital lock-in algorithm can rapidly and simultaneously obtain two-channel images of white light and fluorescence, effectively enhance the SNR of white and fluorescent images, and improve the imaging quality.
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http://dx.doi.org/10.1098/rsos.200779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074948PMC
March 2021

MicroRNA-302s Might Regulate ARL4C-Mediated Gastric Cancer Progression via p53 Signaling: Bioinformatics Analysis and Experiments Validation.

Onco Targets Ther 2021 13;14:2541-2553. Epub 2021 Apr 13.

Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.

Background: Our previous studies demonstrate that ARL4C is the most critical clinical biomarker for gastric cancer (GC) patients among ARL family members (ARLs) and functions as an oncogene in GC. However, its underlying mechanisms in GC need to be further illustrated. In this study, we aim to explore the upstream and downstream molecular mechanisms of ARL4C in GC cells.

Methods: The genetic alteration of ARL4C in GC is analyzed by cBioPortal database. Potential ARL4C-targeted microRNAs (miRs) are predicted by three databases. The high-throughput RNA sequencing is performed to explore the underlying mechanisms of ARL4C in GC cells. The effects of predicted microRNAs on ARL4C, the RNA-sequencing results validation and the biological functions of ARL4C in GC cells are illustrated by in vitro experiments.

Results: Genetic analyses indicate that ARL4C is significantly upregulated in GC, which is not caused by gene amplification. MicroRNAs prediction shows the high relevance between ARL4C and miR-302 members. Moreover, miR-302c or miR-302d transfection reduces ARL4C protein expression in GC cells. Based on the high-throughput RNA sequencing of ARL4C-knockdown cells, enrichment analyses demonstrate that ARL4C is closely related to cell growth and involved in p53 signaling. Moreover, there are strong gene-gene interactions between ARL4C and genes in p53 signaling, and ARL4C downregulation could inhibit the protein expression of MDM2, a critical gene in p53 pathway. Further functional experiments demonstrate that ARL4C silencing leads to cell cycle arrest and increased cell apoptosis in AGS and MKN45 cells.

Conclusion: Our data suggest that miR-302c and miR-302d may function as the upstream regulators of ARL4C. And, ARL4C might promote GC cell cycle progression via regulating p53 signaling. Our findings provide novel insights into the key role of ARL4C and the underlying mechanisms in GC progression, thus facilitating the development of ARL4C-targeted therapy.
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http://dx.doi.org/10.2147/OTT.S282992DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053516PMC
April 2021

ARL4C might serve as a prognostic factor and a novel therapeutic target for gastric cancer: bioinformatics analyses and biological experiments.

J Cell Mol Med 2021 04 16;25(8):4014-4027. Epub 2021 Mar 16.

Department of Gastroenterology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

The ADP-ribosylation factor-like proteins (ARLs) have been proved to regulate the malignant phenotypes of several cancers. However, the exact role of ARLs in gastric cancer (GC) remains elusive. In this study, we systematically investigate the expression status, interactive relations, potential pathways, genetic variations and clinical values of ARLs in GC. We find that ARLs are significantly dysregulated in GC and involved in various cancer-related pathways. Subsequently, machine learning models identify ARL4C as one of the two most significant clinical indicators among ARLs for GC. Furthermore, ARL4C silencing remarkably inhibits the growth and metastasis of GC cells both in vitro and in vivo. Moreover, enrichment analysis indicates that ARL4C is highly correlated with TGF-β1 signalling. Correspondingly, TGF-β1 treatment dramatically increases ARL4C expression and ARL4C knockdown inhibits the phosphorylation level of Smads, downstream factors of TGF-β1. Meanwhile, the coexpression of ARL4C and TGF-β1 worsens the prognosis of GC patients. Our work comprehensively demonstrates the crucial role of ARLs in the carcinogenesis of GC and the specific mechanisms underlying the GC-promoting effects of TGF-β1. More importantly, we uncover the great promise of ARL4C-targeted therapy in improving the efficacy of TGF-β1 inhibitors for GC patients.
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http://dx.doi.org/10.1111/jcmm.16366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051716PMC
April 2021

Vitamin D receptor inhibits EMT via regulation of the epithelial mitochondrial function in intestinal fibrosis.

J Biol Chem 2021 Jan-Jun;296:100531. Epub 2021 Mar 11.

Department of Gastroenterology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

We previously showed that the vitamin D receptor (VDR) plays a crucial role in acute inflammatory bowel disease and that intestinal fibrosis is a common complication of Crohn's disease (CD). Epithelial-mesenchymal transition (EMT) is an important hallmark of fibrogenesis through which epithelial cells lose their epithelial phenotype and transform into mesenchymal cells. It is known that the VDR plays an essential role in epithelial integrity and mitochondrial function, but its role in intestinal fibrosis remains unknown. Here, we investigated whether the VDR is involved in epithelial mitochondrial dysfunction that results in EMT in intestinal fibrosis. Using human CD samples, intestine-specific VDR-KO mice, and fibroblast cellular models, we showed that the expression of the VDR was significantly lower in intestinal stenotic areas than in nonstenotic areas in patients with chronic CD. Genetic deletion of the VDR in the intestinal epithelium exacerbated intestinal fibrosis in mice administered with dextran sulfate sodium or 2,4,6-trinitrobenzene sulfonic acid, two experimental colitis inducers. In addition, we found that vitamin D dietary intervention regulated intestinal fibrosis by modulating the intestinal expression of the VDR. Mechanistically, knocking down the VDR in both CCD-18Co cells and human primary colonic fibroblasts promoted fibroblast activation, whereas VDR overexpression or VDR agonist administration inhibited fibroblast activation. Further analysis illustrated that the VDR inhibited EMT in the HT29 cell model and that mitochondrial dysfunction mediated epithelial integrity and barrier function in VDR-deficient epithelial cells. Together, our data for the first time demonstrate that VDR activation alleviates intestinal fibrosis by inhibiting fibroblast activation and epithelial mitochondria-mediated EMT.
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http://dx.doi.org/10.1016/j.jbc.2021.100531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054199PMC
August 2021

Classification of sleep apnea based on EEG sub-band signal characteristics.

Sci Rep 2021 Mar 12;11(1):5824. Epub 2021 Mar 12.

Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, China.

Sleep apnea syndrome (SAS) is a disorder in which respiratory airflow frequently stops during sleep. Alterations in electroencephalogram (EEG) signal are one of the physiological changes that occur during apnea, and can be used to diagnose and monitor sleep apnea events. Herein, we proposed a method to automatically distinguish sleep apnea events using characteristics of EEG signals in order to categorize obstructive sleep apnea (OSA) events, central sleep apnea (CSA) events and normal breathing events. Through the use of an Infinite Impulse Response Butterworth Band pass filter, we divided the EEG signals of C3-A2 and C4-A1 into five sub-bands. Next, we extracted sample entropy and variance of each sub-band. The neighbor composition analysis (NCA) method was utilized for feature selection, and the results are used as input coefficients for classification using random forest, K-nearest neighbor, and support vector machine classifiers. After a 10-fold cross-validation, we found that the average accuracy rate was 88.99%. Specifically, the accuracy of each category, including OSA, CSA and normal breathing were 80.43%, 84.85%, and 95.24%, respectively. The proposed method has great potential in the automatic classification of patients' respiratory events during clinical examinations, and provides a novel idea for the development of an automatic classification system for sleep apnea and normal events without the need for expert intervention.
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http://dx.doi.org/10.1038/s41598-021-85138-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955071PMC
March 2021

Knockdown of TRIM15 inhibits the proliferation, migration and invasion of esophageal squamous cell carcinoma cells through inactivation of the Wnt/β-catenin signaling pathway.

J Bioenerg Biomembr 2021 04 30;53(2):213-222. Epub 2021 Jan 30.

Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, No.157, Xiwu Road, Xincheng District, Xi'an, 710004, Shaanxi Province, China.

TRIM15 is a member of tripartite motif-containing protein (TRIM) protein family, which plays important roles in several cancers. The aim of the present study was to evaluate the role of TRIM15 in esophageal squamous cell carcinoma (ESCC). Our results showed that TRIM15 was upregulated in human ESCC tissues and cell lines. In vitro studies showed that knockdown of TRIM15 significantly inhibited the proliferation, migration, and invasion of ESCC cells. Knockdown of TRIM15 caused a significant increase in E-cadherin expression, as well as decreases in expression of N-cadherin and Vimentin proteins. Moreover, in vivo assay proved that tumor growth was suppressed by knockdown of TRIM15. Furthermore, the protein expression levels of β-catenin, C-myc, and CyclinD1 were markedly decreased in sh-TRIM15-infected ESCC cells. Additionally, treatment with LiCl reversed the inhibitory effects of TRIM15 knockdown on ESCC cells. In conclusion, these findings indicated that knockdown of TRIM15 blocked the growth and metastasis of ESCC in part through inhibiting the Wnt/β-catenin signaling pathway. Thus, TRIM15 might serve as a promising therapeutic target for ESCC.
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http://dx.doi.org/10.1007/s10863-021-09872-wDOI Listing
April 2021

Rome III, Rome IV, and Potential Asia Symptom Criteria for Functional Dyspepsia Do Not Reliably Distinguish Functional From Organic Disease.

Clin Transl Gastroenterol 2020 12;11(12):e00278

Department of Gastroenterology, The Second Affiliated Hospital, Xi'an Jiaotong University, Shaanxi, China.

Introduction: Although the Rome criteria were created primarily for research purposes, it was an important question whether the Rome criteria can distinguish organic dyspepsia from functional dyspepsia (FD). We evaluated the accuracy of the Rome IV criteria in identifying patients with FD and compared the differences between the Rome IV, Rome III, and potential Asia criteria in identifying patients with FD.

Methods: In this cross-sectional study, we analyzed data from patients who met the inclusion and exclusion criteria from March 2018 to January 2019 at 2 tertiary hospitals.

Results: A total of 600 patients were enrolled in this study, including 381 individuals met the Rome IV criteria for FD, 438 individuals met the Rome III criteria for FD, and 525 individuals met the potential Asia criteria for FD. The Rome IV criteria identified patients with FD with 67.3% sensitivity and 38.4% specificity, and the positive and negative likelihood ratios of FD identified by Rome IV criteria were 1.09 (95% confidence interval 0.97-1.24) and 0.85 (95% confidence interval 0.67-1.08), respectively. There was no significant difference in the area under Rome IV, Rome III, or potential Asia criteria receiver operating characteristic curves in identifying FD (P > 0.05).

Discussion: The Rome IV criteria were no better than the Rome III or potential Asia criteria in identifying FD and were not helpful in identifying patients with FD. Hence, although the Rome criteria remain useful for defining patients with FD for inclusion into clinical treatment trials, they should not be used for diagnosing FD.
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http://dx.doi.org/10.14309/ctg.0000000000000278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7721216PMC
December 2020

Knockdown of PDIA6 Inhibits Cell Proliferation and Enhances the Chemosensitivity in Gastric Cancer Cells.

Cancer Manag Res 2020 2;12:11051-11062. Epub 2020 Nov 2.

Gastroenterology Department, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, People's Republic of China.

Background: Protein disulfide isomerase A6 (PDIA6), a member of the disulfide isomerase (PDI) family, has been reported to be closely associated with progression of various cancers. However, the specific effects of PDIA6 on gastric cancer (GC) remain unclear. In this study, we investigated the expression pattern and biological functions of PDIA6 in GC.

Materials And Methods: The CCK-8 assay was carried out to examine cell proliferation and cisplatin cytotoxicity. The Western blot analysis was used to measure the protein expression of PDIA6, Wnt3a and β-catenin. The xenograft tumor assay was performed to evaluate the in vivo effect of PDIA6 on GC cell proliferation and chemoresistance.

Results: PDIA6 was significantly elevated in GC tissues and cell lines. Down-regulation of PDIA6 inhibited GC cell proliferation and chemoresistance to cisplatin while up-regulation of PDIA6 promoted the proliferation and chemoresistance of GC cells. Besides, PDIA6 regulated the chemosensitivity of GC cells to cisplatin in vivo. Mechanically, PDIA6 served as a regulator of the Wnt/β-catenin signaling pathway by affecting the protein expression of Wnt3a and β-catenin in GC cells. Additionally, Wnt activator reversed the inhibitory effect of PDIA6 knockdown on cisplatin resistance in GC cells.

Conclusion: These findings provided new insight into the potential role of PDIA6 as a promising target for drug resistance in GC chemotherapy.
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http://dx.doi.org/10.2147/CMAR.S267711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7646476PMC
November 2020

Deep learning algorithms for brain disease detection with magnetic induction tomography.

Med Phys 2021 Feb 18;48(2):745-759. Epub 2020 Dec 18.

School of Life Sciences, Tianjin Polytechnic University, 399 Binshui West Street, Xiqing District, Tianjin, 300387, P.R.China.

Purpose: In order to improve the reconstruction accuracy of magnetic induction tomography (MIT) and achieve fast imaging especially in the detection of cerebral hemorrhage, artificial intelligence algorithms are proposed to improve the accuracy of MIT inverse problem.

Methods: According to the standard geometric data of human head, a three-dimensional (3D) head model containing four layer tissues is established for brain image reconstruction of MIT. Four deep learning (DL) networks, including restricted Boltzmann machine (RBM), deep belief network (DBN), stacked autoencoder (SAE), and denoising autoencoder (DAE), are used to solve the nonlinear reconstruction problem of MIT, and the reconstruction results of DL networks and back-projection algorithm are compared. Finally, in order to verify the practical value of DL algorithms, the phantom experiment is carried out with MIT detection system.

Results: Using the nonlinear data learning ability of DL algorithms, the rapid and high-precision imaging of cerebral hemorrhage can be realized. Compared with the back-projection algorithm, the DL improves the artifact and the accuracy of the reconstruction image. The location and volume of bleeding can be reconstructed and the prediction time reaches 20 ms. Moreover, the anti-noise performance of the networks can reach 20 dB.

Conclusions: The DL can effectively improve the reconstruction accuracy and prediction speed of the image when it is applied to the reconstruction of cerebral hemorrhage in MIT. This feasibility study MIT to be a potential technology for brain diseases to fully meet the needs of accurate, rapid, and low-cost clinical diagnosis and continuous monitoring.
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http://dx.doi.org/10.1002/mp.14558DOI Listing
February 2021

Development of a spermatogonia cryopreservation protocol for blue catfish, Ictalurus furcatus.

Cryobiology 2020 12 13;97:46-52. Epub 2020 Oct 13.

School of Fisheries, Aquaculture and Aquatic Sciences, Auburn University, Auburn, AL, 36849, USA. Electronic address:

Sustainability of channel catfish, Ictalurus punctatus ♀ × blue catfish, Ictalurus furcatus ♂ hybrid aquaculture relies on new innovative technologies to maximize fry output. Transplanting spermatogonial stem cells (SSCs) from blue catfish into channel catfish hosts has the potential to greatly increase gamete availability and improve hybrid catfish fry outputs. Cryopreservation would make these cells readily accessible for xenogenesis, but a freezing protocol for blue catfish testicular tissues has not yet been fully developed. Therefore, the objectives of this experiment were to identify the best permeating [dimethyl sulfoxide (DMSO), ethylene glycol (EG), glycerol, methanol] and non-permeating (lactose or trehalose with egg yolk or BSA) cryoprotectants, their optimal concentrations, and the best freezing rates (-0.5, -1.0, -5.0, -10 °C/min until -80 °C) that yield the highest number of viable type A spermatogonia cells. Results showed that all of these factors had significant impacts on post-thaw cell production and viability. DMSO was the most efficient permeating cryoprotectant at a concentration of 1.0 M. The optimal concentration of each cryoprotectant depended on the specific cryoprotectant due to interactions between the two factors. Of the non-permeating cryoprotectants, 0.2 M lactose with egg yolk consistently improved type A spermatogonia production and viability beyond that of the 1.0 M DMSO control. The overall best freezing rate was consistent at -1 °C/min, but similar results were obtained using -0.5 °C/min. Overall, we recommend cryopreserving blue catfish testicular tissues in 1.0 M DMSO with 0.2 M lactose and egg yolk at a rate of either -0.5 or -1 °C/min to achieve the best cryopreservation outcomes. Continued development of cryopreservation protocols for blue catfish and other species will make spermatogonia available for xenogenic applications and genetic improvement programs.
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http://dx.doi.org/10.1016/j.cryobiol.2020.10.010DOI Listing
December 2020

Technologies for magnetic induction tomography sensors and image reconstruction in medical assisted diagnosis: A review.

Rev Sci Instrum 2020 Sep;91(9):091501

School of Life Sciences, Tianjin Polytechnic University, 399 Binshui West Street, Xiqing District, Tianjin 300387, People's Republic of China.

Magnetic induction tomography (MIT) is a non-invasive and non-contact imaging technology, which can be used in medical diagnosis by reconstructing the electrical distribution of biological tissues. Unlike other large medical imaging equipment, the device of MIT is with small size and low cost. The theoretical basis of MIT is by measuring the phase difference of magnetic flux density generated around the imaging objects, analyzing the eddy current distribution, and then using the reconstruction algorithms to obtain the electrical characteristic distribution of the object. This review introduces the development of imaging systems and the reconstruction algorithms of MIT as a medical assisted diagnostic technology, including the optimal design of the sensors, the excitation methods of the system, the calculation methods of the eddy current, and the improved methods of different reconstruction algorithms.
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http://dx.doi.org/10.1063/1.5143895DOI Listing
September 2020

Scalp-acupuncture for patients with hemiplegic paralysis of acute ischaemic stroke: a randomized controlled clinical trial.

J Tradit Chin Med 2020 10;40(5):845-854

The school of Acupuncture and Massage, Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China.

Objective: To evaluate the efficacy of scalp-acupuncture on subjects with hemiplegic paralysis of acute ischaemic stroke (AIS).

Methods: One hundred and twenty patients with hemiplegic paralysis of 1 to 7 d post stroke, aged 40 to 75 years, were randomly allocated to receive either standard care (control group) or standard care plus 30 min of scalp-acupuncture applied to the bilateral anterior oblique line of the vertex-temporal (MS6) for 14 d (6 d/week) (trial group). The outcome measures included the National Institutes of Health Stroke scale (NIHSS) for neurological deficits, the Fugl-Meyer assessment (FMA) for limb impairment, and Barthel index (BI) for activities of daily living before and after intervention. The manual muscle test (MMT) was assessed at pre-intervention, at the first post-intervention immediately, and at the 14th day after intervention commencement. Measurements were recorded by a blinded investigator at different time points after initiating the intervention.

Results: The trial group had a greater increase in MMT (P < 0.05), FMA, and BI scores (P < 0.01), and a greater decrease in NIHSS scores (P < 0.01) from pre-intervention to post-intervention, and the control group had a greater increase in MMT scores (P < 0.05), and a greater decrease in NIHSS scores(P < 0.01) from pre-intervention to post-intervention. The improvement in MMT (P < 0.01), FMA, BI (P < 0.05), and NIHSS (P < 0.01) scores in the trial group was superior to that of the control group. Meanwhile, scalp-acupuncture intervention had an immediate effect on myodynamia of patients with hemiplegic paralysis after acute ischaemic stroke in this randomized controlled trial.

Conclusion: The early scalp-acupuncture intervention after stroke effectively increased myodynamia of the affected limbs, improved neurological deficit degrees, and daily living ability.
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http://dx.doi.org/10.19852/j.cnki.jtcm.2020.05.015DOI Listing
October 2020

Design of a scanning magnetic induction phase measurement system for respiratory monitoring.

Rev Sci Instrum 2020 Aug;91(8):083705

School of Life Sciences, Tiangong University, 399 Binshui West Street, Xiqing District, Tianjin 300387, People's Republic of China.

The commonly used respiratory monitoring methods in clinical medicine are chest belt or ventilators, which are not easy to carry and cumbersome to operate. In order to solve this problem, a low-cost and portable magnetic induction phase detection system for respiratory monitoring is proposed. In this study, a magnetic induction tomography system for respiration detection is established, and the phase sensitivity of the system to conductive object is evaluated through a series of experiments. At the same time, phantom experiments are carried out to simulate the respiratory process, and the phase monitoring indicators are collected to describe different respiratory states. The experimental results show that the phase detection results are consistent with the changes in the respiratory cycle. The signal-to-noise ratio of the system is 79 dB. It proves the feasibility of using magnetic induction phase measurement in respiratory monitoring and provides a new detection method of respiratory monitoring.
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http://dx.doi.org/10.1063/5.0010603DOI Listing
August 2020

Portable and multiplexed lateral flow immunoassay reader based on SERS for highly sensitive point-of-care testing.

Biosens Bioelectron 2020 Nov 20;168:112524. Epub 2020 Aug 20.

Beijing Institute of Radiation Medicine, Beijing, 100850, PR China; Beijing Key Laboratory of New Molecular Diagnosis Technologies for Infectious Diseases, Beijing, 100850, PR China. Electronic address:

A portable surface-enhanced Raman scattering (SERS)-based lateral flow immunoassay (LFIA) reader with multiplexed detection was developed using an integrated LFIA reaction column. The proposed LFIA reader was designed to simultaneously detect multiple samples or samples with multiple biomarkers. With the integrated LFIA reaction column, we achieved the specific detection of alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and prostate-specific antigen (PSA) with a detection limit of 0.01 ng/mL, which was three orders of magnitude lower than that of the visual signal. We also investigated the uniformity of channels based on an eight-channel integrated LFIA reaction column. The relative standard deviation values of the SERS intensity of the eight-channel for measuring the AFP, CEA, and PSA antigens at 1323 cm were 13%, 4.8%, and 5%, respectively. We detected 45 clinical serum samples of the three antigens using the proposed portable SERS-based LFIA reader to further confirm its applicability to clinical samples. The SERS signals of the positive sera were higher than those of the negative sera and their thrice standard deviation. This result indicated the practicality of the developed integrated reaction column and the proposed portable and multiplexed Raman reader. This work provides a new high-sensitivity, multiplexed, and automated SERS-based LFIA detector for use in the point-of-care setting.
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http://dx.doi.org/10.1016/j.bios.2020.112524DOI Listing
November 2020

Effect of photobiomodulation on CCC-ESF reactive oxygen species steady-state in high glucose mediums.

Lasers Med Sci 2021 Apr 9;36(3):555-562. Epub 2020 Jul 9.

School of Life Sciences, Tiangong University, Xiqing District, Binshui West Road, Tianjin, 300387, China.

Delayed wound healing is one of the most challenging complications of diabetes mellitus (DM) in clinical medicine, and it is related to the excessive generation of reactive oxygen species (ROS). Photobiomodulation (PBM) can promote wound healing in many ways, so it can be used as a method for the treatment of delayed healing of DM wounds. In this study, we investigated the effect of PBM on ROS homeostasis in human embryonic skin fibroblast cells (CCC-ESFs) cultured in high glucose concentrations. The CCC-ESFs were cultured in vitro and divided into two groups, including the control group and the 635 nm laser irradiation group. After 2 days of high glucose treatment, the experimental group was irradiated with different doses of laser for 3 days. First, we measured the cellular proliferation, and the results showed that laser irradiation could promote cellular proliferation. Then, we measured the generation of ROS, the activities of total superoxide dismutase (SOD), and total antioxidant capacity (TAC) of the cells; the results showed that high glucose destroyed cells by inducing high concentration of ROS, the balance of oxidation, and antioxidation cause oxidative stress damage to cells. PBM can increase the antioxidant capacity of cells, reducing the high concentration of ROS induced by high glucose. Finally, we measured the levels of mitochondrial membrane potential (∆ψ) and the secretion of nuclear factor kappa-B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β); the results showed that PBM can reduce apoptosis and regulate the inflammatory state. We conclude that PBM can maintain the ROS homeostasis, increase the TAC of cells, and trigger the cellular proliferation, and the response of CCC-ESFs to PBM was dose-dependent.
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http://dx.doi.org/10.1007/s10103-020-03057-4DOI Listing
April 2021

Continuous monitoring method of cerebral subdural hematoma based on MRI guided DOT.

Biomed Opt Express 2020 Jun 11;11(6):2964-2975. Epub 2020 May 11.

School of Life Sciences, Tiangong University, Tianjin 300387, China.

Cerebral subdural hematomas due to trauma can easily worsen suddenly due to the rupture of blood vessels in the brain after the condition is stabilized. Therefore, continuous monitoring of the size of cerebral subdural hematomas has important clinical significance. To achieve fast, real-time, noninvasive, and accurate monitoring of subdural hematomas, a cerebral subdural hematoma monitoring method combining brain magnetic resonance imaging (MRI) image guidance, diffusion optical tomography technology, and deep learning is proposed in this manuscript. First, an MRI brain image is segmented to obtain a three-dimensional multi-layer brain model with structures and parameters matching a real brain. Then, a near-infrared light source and detectors (source-detector separations ranging from 0.5 to 6.5 cm) were placed on the model to achieve fast, real-time and noninvasive acquisition of intracranial hematoma information. Finally, a deep learning method is used to obtain accurate reconstructed images of cerebral subdural hematomas. The experimental results show that the reconstruction effect of stacked auto-encoder with the mean volume error of 0.1 ml is better than the result reconstructed by algebraic reconstruction techniques with the mean volume error of 0.9 ml. Under different signal-to-noise ratios, the curve fitting R between the actual blood volume of a simulated hematoma and a reconstructed hematoma is more than 0.95. We conclude that the proposed monitoring method can realize fast, noninvasive, real-time, and accurate monitoring of subdural hematomas, and can provide a technical basis for continuous wearable subdural hematoma monitoring equipment.
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http://dx.doi.org/10.1364/BOE.388059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316016PMC
June 2020

[Indoor simulation training system for brain-controlled wheelchair based on steady-state visual evoked potentials].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi 2020 Jun;37(3):502-511

Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300192, P.R.China.

Brain-controlled wheelchair (BCW) is one of the important applications of brain-computer interface (BCI) technology. The present research shows that simulation control training is of great significance for the application of BCW. In order to improve the BCW control ability of users and promote the application of BCW under the condition of safety, this paper builds an indoor simulation training system based on the steady-state visual evoked potentials for BCW. The system includes visual stimulus paradigm design and implementation, electroencephalogram acquisition and processing, indoor simulation environment modeling, path planning, and simulation wheelchair control, etc. To test the performance of the system, a training experiment involving three kinds of indoor path-control tasks is designed and 10 subjects were recruited for the 5-day training experiment. By comparing the results before and after the training experiment, it was found that the average number of commands in Task 1, Task 2, and Task 3 decreased by 29.5%, 21.4%, and 25.4%, respectively ( < 0.001). And the average number of commands used by the subjects to complete all tasks decreased by 25.4% ( < 0.001). The experimental results show that the training of subjects through the indoor simulation training system built in this paper can improve their proficiency and efficiency of BCW control to a certain extent, which verifies the practicability of the system and provides an effective assistant method to promote the indoor application of BCW.
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http://dx.doi.org/10.7507/1001-5515.201906025DOI Listing
June 2020

Downregulation of OCTN2 by cytokines plays an important role in the progression of inflammatory bowel disease.

Biochem Pharmacol 2020 08 21;178:114115. Epub 2020 Jun 21.

Laboratory of Drug Metabolism and Pharmaceutical Analysis, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China. Electronic address:

Inflammatory bowel diseases (IBD) are characterized by chronic relapsing disorders of the gastrointestinal tract. OCTN2 (SLC22A5) and its substrate l-carnitine (l-Car) play crucial roles in maintaining normal intestinal function. An aim of this study was to delineate the expression alteration of OCTN2 in IBD and its underlying mechanism. We also investigated the impact of OCTN2 on IBD progression and the possibility of improving IBD through OCTN2 regulation. Our results showed decreased OCTN2 expression levels and l-Car content in inflamed colon tissues of IBD patients and mice, which negatively correlated with the degree of colonic inflammation in IBD mice. Mixed proinflammatory cytokines TNF-α, IL-1β and IFNγ downregulated the expression of OCTN2 and subsequently reduced the l-Car content through PPARγ/RXRα pathways in FHC cells. OCTN2 silencing reduced the proliferation rate of the colon cells, whereas OCTN2 overexpression increased the proliferation rate. Furthermore, the ability of PPARγ agonist, luteolin, to increase OCTN2 expression resulted in the alleviation of colonic inflammatory responses. In conclusion, OCTN2 was downregulated in IBD by proinflammatory cytokines via the PPARγ/RXRα pathways, which reduced l-Car concentration and subsequently induced IBD deterioration. Upregulation of OCTN2 by the PPARγ agonist alleviated colonic inflammation. Our findings suggest that, OCTN2 may serve as a therapeutic target for IBD therapy.
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http://dx.doi.org/10.1016/j.bcp.2020.114115DOI Listing
August 2020

Indoor Simulated Training Environment for Brain-Controlled Wheelchair Based on Steady-State Visual Evoked Potentials.

Front Neurorobot 2019 8;13:101. Epub 2020 Jan 8.

Institute of Biomedical Engineering, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.

Brain-controlled wheelchair (BCW) has the potential to improve the quality of life for people with motor disabilities. A lot of training is necessary for users to learn and improve BCW control ability and the performances of BCW control are crucial for patients in daily use. In consideration of safety and efficiency, an indoor simulated training environment is built up in this paper to improve the performance of BCW control. The indoor simulated environment mainly realizes BCW implementation, simulated training scenario setup, path planning and recommendation, simulated operation, and scoring. And the BCW is based on steady-state visual evoked potentials (SSVEP) and the filter bank canonical correlation analysis (FBCCA) is used to analyze the electroencephalography (EEG). Five tasks include individual accuracy, simple linear path, obstacles avoidance, comprehensive steering scenarios, and evaluation task are designed, 10 healthy subjects were recruited and carried out the 7-days training experiment to assess the performance of the training environment. Scoring and command-consuming are conducted to evaluate the improvement before and after training. The results indicate that the average accuracy is 93.55% and improves from 91.05% in the first stage to 96.05% in the second stage ( = 0.001). Meanwhile, the average score increases from 79.88 in the first session to 96.66 in the last session and tend to be stable ( < 0.001). The average number of commands and collisions to complete the tasks decreases significantly with or without the approximate shortest path ( < 0.001). These results show that the performance of subjects in BCW control achieves improvement and verify the feasibility and effectiveness of the proposed simulated training environment.
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http://dx.doi.org/10.3389/fnbot.2019.00101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6961652PMC
January 2020

Osteopontin expression is associated with progression and adverse prognosis in patients with resectable gastrointestinal stromal tumor.

Int J Clin Exp Pathol 2019 1;12(4):1385-1390. Epub 2019 Apr 1.

Department of Intensive Care Unit, The First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou, Zhejiang Province, P. R. China.

Objectives: Osteopontin (OPN) is reported to be particularly associated with the progression of several human malignancies. This study was designed to examine the clinicopathologic significance of OPN in gastrointestinal stromal tumor (GISTs).

Methods: The level of OPN expression in a large cohort of resectable GISTs was evaluated with immunohistochemistry. Its correlation with the clinicopathologic parameters of patients with resectable GISTs was analyzed. A survival analysis was performed to evaluate the prognostic significance of OPN expression using the Kaplan-Meier method.

Results: In 108 patients with resectable GISTs, the most high-risk GISTs had a strong level of OPN expression. Strong OPN expression was also significantly associated with tumor size, mitosis, and recurrence, but not gender and age. Patients with weak OPN expression had a relatively longer disease-free survival compared to patients with strong OPN expression.

Conclusions: OPN expression is a putative marker for tumor progression and an adverse prognosis in GISTs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947051PMC
April 2019

Letter to the Editor: The Association Between Diabetes and Hepatocellular Carcinoma in Patients With Cirrhosis Caused by Nonalcoholic Fatty Liver Disease.

Hepatology 2020 07;72(1):363-364

Department of Gastroenterology, The Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, PR China.

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http://dx.doi.org/10.1002/hep.31099DOI Listing
July 2020

TOB1 suppresses proliferation in K-Ras wild-type pancreatic cancer.

Cancer Med 2020 02 31;9(4):1503-1514. Epub 2019 Dec 31.

Department of Gastroenterology, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China.

TOB1 participates in various kinds of cancers. However, its role in pancreatic cancer has rarely been reported. In this study, we explored the expression and mechanisms of TOB1 in regulating the malignant phenotype of pancreatic cancer cells. TOB1 expression was determined by data mining and immunohistochemistry (IHC), and its localization was observed by immunofluorescence. CCK-8 cell proliferation, colony formation, flow cytometric, transwell migration, and Western blot (WB) assays were used to examine how it impacts the malignant phenotype of pancreatic cancer. Furthermore, Foxa2 binding to TOB1 was tested by dual-luciferase reporter assays, and RNA-Seq was performed to identify signaling pathways. We found TOB1 was downregulated in pancreatic cancer tissues and was mainly located in the cytoplasm. TOB1 overexpression reduced the proliferation of K-Ras wild-type pancreatic cancer cells but made no difference to cell migration and invasion. Foxa2 overexpression significantly enhanced TOB1 promoter activity. Moreover, overexpressing TOB1 substantially enriched the calcium pathway in K-Ras wild-type pancreatic cancer cells. In conclusion, TOB1 may suppress the proliferation of K-Ras wild-type pancreatic cancer cells by regulating calcium pathway genes.
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http://dx.doi.org/10.1002/cam4.2756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013073PMC
February 2020
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