ObjectiveTo investigate the role and mechanism of Go-Ichi-Ni-San complex subunit 1 （GINS1） in the progression of hepatocellular carcinoma （HCC） and the development of chemotherapy resistance. MethodsThe tumor database GEPIA2 was used to analyze the differential expression of GINS1 between HCC patients and healthy individuals， and pathological tissue samples were collected from 40 HCC patients who were admitted to The Affiliated Tumor Hospital of Xinjiang Medical University and the First Affiliated Hospital of Xinjiang Medical University from May 2017 to January 2021. Immunohistochemical staining was used to measure the difference in the expression of GINS1 between HCC tissue and corresponding adjacent tissue， and the correlation between the expression level of GINS1 and the clinical TNM stage of HCC was analyzed. Western blot was also used to measure the difference in the expression of GINS1 between HCC Huh7/Hep3B/Li-7/MHCC97H cell lines and normal human QSG7701 hepatocytes. The method of lentivirus transfection was used to establish the MHCC97H cell line with stable GINS1 knockdown and its negative control cell line. CCK-8 assay and colony formation assay were used to measure cell proliferative capacity； scratch assay was used to measure cell migration ability； Transwell assay was used to measure cell invasion ability； cells were treated with oxaliplatin to measure their sensitivity to chemotherapy drugs. Nude mice were used to establish a tumor-bearing model and observe the effect of GINS1 knockdown on the growth of HCC in vivo. Western Blot was used to measure the expression levels of the proteins associated with the Notch pathway and the JAK/STAT pathway. The cells were treated with the Notch receptor agonist Jagged-1 to analyze the association between GINS1 and the Notch/JAK/STAT pathway. The independent-samples t test was used for comparison of continuous data between two groups； a one-way analysis of variance was used for comparison between multiple groups， and the least significant difference t-test was used for further comparison between two groups. ResultsThe expression of GINS1 was upregulated in HCC patients， HCC tissue， and HCC cell lines （all P<0.05）， and the expression level of GINS1 was positively correlated with the clinical TNM stage of HCC （r=0.822， P=0.011）. Compared with the negative control cells， the GINS1-knockdown MHCC97H cells showed significant reductions in proliferation， migration， and invasion activities （all P<0.01） and a significantly enhanced sensitivity to oxaliplatin （P<0.01）. Compared with the nude mice in the control group， GINS1 knockdown caused significant inhibition of tumor weight and volume in vivo in nude mice （all P<0.001）. Compared with the negative control cells， the GINS1-knockdown MHCC97H cells showed significant reductions in the expression levels of Notch1， Notch3， p-JAK2， and p-STAT3 （all P<0.05）， while there were no significant differences in the overall expression levels of JAK2 and STAT3 （P>0.05）. After Jagged-1 treatment， the GINS1-knockdown MHCC97H cells showed significant increases in proliferation， migration， and invasion activities and a significant reduction in sensitivity to oxaliplatin， as well as significant increases in the levels of p-JAK2 and p-STAT3 （all P<0.05）. ConclusionGINS1 is upregulated in HCC and can promote HCC progression and chemotherapy resistance through the Notch/JAK2/STAT3 pathway.

Objective:To explore the effect of β-galactoside α-2-6sialyltransferase1(ST6GAL1)on glycolysis,migration and invasion of colorectal cancer(CRC)HCT116 cells and its possible molecular mechanisms.Methods:The difference in the expression of ST6GAL1 in CRC patients and healthy people was analyzed using the GEPIA2 database.WB was performed to detect the differences in the expressions of ST6GAL1 in CRC cell lines HCT116,SW480,Caco-2,HT29,LoVo and human normal colon epithelial cell line NCM460.The difference in the expressions of ST6GAL1 in CRC tissues and corresponding adjacent tissues was analyzed by immunohistochemistry.HCT116 cell lines with stably knocked down or overexpressed ST6GAL1 were constructed by lentivirus transfection.Cell migration ability was detected by scratch test.Cell invasion ability was detected by Transwell test.WB assay was performed to detect the expression levels of cell glycolysis-related proteins and Notch1 intracellular domain(Notch1 ICD)as well as the phosphorylation level of PI3K/AKT/mTOR pathway.The expression level of Notch1 ICD and its entry into nucleus were observed by immunofluorescence assay.The Notch1 receptor agonist Jagged1 was added to HCT116 cells,and the expression levels of glycolysis-related proteins and Notch1 ICD and PI3K/AKT/mTOR pathway phosphorylation level were detected by WB.Results:The expression of ST6GAL1 was up-regulated in CRC tissues and cells(all P<0.05).Compared with the control and overexpression groups,knockdown of ST6GAL1 resulted in significantly lower levels of Notch1 ICD expression and PI3K/AKT/mTORC1 phosphorylation in HCT116 cells,lower levels of cellular glycolysis-related protein expressions and weaker cell migration and invasion abilities(all P<0.05).Overexpression of ST6GAL1 increased Notch1 ICD expression levels within HCT116 cells and promoted their entry into the nucleus.Cell glycolysis-related protein expression levels were elevated(all P<0.05).Cell migration and invasion abilities were enhanced(all P<0.05).Conclusion:ST6GAL1 activates the PI3K/AKT/mTORC1 pathway through activation of Notch1 receptor and phosphorylation,thus enhancing the glycolytic level and migration and invasion abilities of CRC cells.

Objective:To investigate the relationship between the cerebral small vascular disease (CSVD) total burden and the imaging markers and the degree of unilateral middle cerebral artery (MCA) stenosis.Methods:The study was a cross-sectional study. Clinical and imaging data of patients with chronic unilateral MCA stenosis who underwent multimodal MRI from October 2015 to January 2019 in the First Medical Center of PLA General Hospital were retrospectively analyzed. A total of 261 patients were included, 187 males and 74 females. According to the degree of MCA stenosis, the patients were divided into 102 cases in severe stenosis-occlusion group (stenosis degree ≥70%) and 159 cases in mild-moderate stenosis group (stenosis degree <70%). CSVD imaging marker scores (including white matter hyperintensity, perivascular space, cerebral microbleed, and lacune of presumed vascular origin) were assessed according to the ?standards for reporting vascular changes on neuroimaging 1 in the 2 groups, and the CSVD total burden score was calculated. Mann-Whitney U test was used to compare the indicators between the two groups, and the CSVD total burden score and imaging marker scores were ultimately included in a multifactorial binary logistic regression to assess the association of CSVD imaging markers with severe stenosis-occlusion of the MCA after adjusting for vascular risk factors (age, gender, drinking, smoking, hypertension, hyperlipidemia, atrial fibrillation and coronary heart disease). Results:There were significant differences in the CSVD total burden, centrum semiovale perivascular space and lacune of presumed vascular origin score between the mild-to-moderate stenosis group and the severe stenosis-occlusion group (all P<0.05), and none of the differences in the remaining imaging marker scores were statistically significant (all P>0.05). Multivariate binary logistics regression analysis showed CSVD total burden score ( OR=1.300, 95% CI 1.047-1.613, P=0.017), centrum semiovale perivascular space score ( OR=2.099, 95% CI 1.540-2.860, P<0.001) and lacune of presumed vascular origin score ( OR=2.609, 95% CI 1.294-5.261, P=0.007) were independent associated with severe stenosis-occlusion of MCA. Conclusion:The higher CSVD total burden score, centrum semiovale perivascular space score and lacune of presumed vascular origin score are associated with severe stenosis-occlusion of MCA.

Objective:To explore the value of fast susceptibility weighted imaging (SWI) generated by a deep learning model in assessment of acute ischemic stroke (AIS).Methods:From January 2019 to January 2021, 118 AIS patients [75 males and 43 females, aged 23-100 (66±14) years] who underwent MR examination and SWI sequence scanning within 24 h of symptom onset in the First Medical Center of PLA General Hospital were retrospectively analyzed. MATLAB ′s randperm function was used to divide 118 patients into a training set of 96 cases and a test set of 22 cases at a ratio of 8∶2. Fourty-seven AIS patients [38 males and 9 females, aged 16-75 (58±12) years] from one center of a multicenter study were selected to build the external validation set. SWI image and filtered phase image were combined into complex value image as full sampling reference image. Undersampled SWI images were obtained by retrospective undersampling of reference fully sampled images, and the undersampling multiple was five times which could save 80% of the scanning time, then the complex-valued convolutional neural network (ComplexNet) was used to develop reconstruct fast SWI. Interclass correlation coefficient (ICC) or Kappa tests were used to compare the consistency of image quality and the diagnostic consistency for the presence of susceptibility vessel sign (SVS), cerebral microbleeds and asymmetry of cerebral deep medullary veins (DMVs) in AIS patient on fully sampled SWI and fast SWI based on ComplexNet.Results:In test set, score of image quality was 4.5±0.6 for fully sampled SWI image and 4.6±0.7 for fast SWI based on ComplexNet, and coefficient was excellent (ICC=0.86, P<0.05). Full sampling SWI had good agreement with fast SWI based on ComplexNet in detecting SVS (Kappa=0.79, P<0.05), microbleeds (Kappa=0.86, P<0.05), and DMVs asymmetry (Kappa=0.82, P<0.05) in AIS patients. In the external validation set, score of image quality was 4.1±1.0 for fully sampled SWI image and 4.0±0.9 for fast SWI based on ComplexNet, and coefficient was excellent (ICC=0.97, P<0.05). Full sampling SWI had good agreement with fast SWI based on ComplexNet in detecting SVS (Kappa=0.74, P<0.05), microbleeds (Kappa=0.83, P<0.05), and DMVs asymmetry (Kappa=0.74, P<0.05) in AIS patients. Conclusions:Deep learning techniques can significantly accelerate the speed of SWI, and the consistency of image quality and detected AIS signs between fast SWI based on ComplexNet and fully sampled SWI is good. The fast SWI based on ComplexNet can be applied to the radiographic assessment of clinical AIS patients

Objective:To evaluate the clinical value of different shimming methods at 7.0 T MR in two-dimensional (2D) and three-dimensional (3D) T 2WI. Methods:Totally 23 healthy volunteers were prospectively recruited from the First Medical Center of PLA General Hospital from November, 2022 to May, 2023, including 12 volunteers who underwent 2D shimming mode and 14 volunteers who underwent 3D shimming mode. 2D shimming mode included patient-specific (PS) mode, direct signal control (DSC) mode, the standard circularly polarized (CP) mode, and volume-specific (VS) mode. 3D shimming mode included universal pulses (UP) mode and CP mode. The image quality for the subtentorial and supratentorial region was assessed by the subjective image quality score and signal-to-noise ratio. Comparisons of quantitative indices between multiple groups were performed using repeated-measures ANOVA or Friedman′s test; comparisons of quantitative indices between 2 groups were performed using paired-samples t test or Wilcoxon signed-rank test. Results:The image quality of subtentorial region and SNR was significant differences in 2D T 2WI with PS mode, DSC mode, CP mode and VS mode ( F=26.74, P<0.001; F=28.24, P<0.001), and the image quality score and SNR of PS mode, DSC mode, VS mode were better than CP mode ( P<0.05). In 2D T 2WI, there was no significant difference in image quality score and SNR of supratentorial region in PS mode, DSC mode, CP mode ( P>0.05). Besides, in 3D T 2WI, the image quality score for subtentorial and supratentorial region of UP mode were better than those of CP mode ( Z=-2.74, P=0.006; Z=-3.24, P=0.001); SNR of subtentorial region was significantly better in UP mode than those in CP mode ( t=3.49, P=0.004). But there was no significant difference in SNR of supratentorial region between the UP mode and CP mode in 3D T 2WI ( P>0.05). Conclusion:T 2WI with different shimming methods at 7.0 T MR can provide data support for the clinical application, which is helpful for the accurate diagnosis of patients with subtentorial lesions.