Abstract Background and aims: The recurrence and metastasis of hepatocellular carcinoma (HCC) are mainly caused by microvascular invasion (MVI). Our study aimed to uncover the cellular atlas of MVI + HCC and investigate the underlying immune infiltration patterns with radiomics features. Methods Three MVI positive HCC and three MVI negative HCC samples were collected for single-cell RNA-seq analysis. 26 MVI positive HCC and 30 MVI negative HCC tissues were underwent bulk RNA-seq analysis. For radiomics analysis, radiomics features score (Radscore) were built using preoperative contrast MRI for MVI prediction and overall survival prediction. We deciphered the metabolism profiles of MVI + HCC using scMetabolism and scFEA. The correlation of Radscore with the level of APOE + macrophages and iCAFs was identified. Whole Exome Sequencing (WES) was applied to distinguish intrahepatic metastasis (IM) and multicentric occurrence (MO). Transcriptome profiles were compared between IM and MO. Results Elevated levels of APOE + macrophages and iCAFs were detected in MVI + HCC. There was a strong correlation between the infiltration of APOE + macrophages and iCAFs, as confirmed by immunofluorescent staining. MVI positive tumors exhibited increased lipid metabolism, which was attributed to the increased presence of APOE + macrophages. APOE + macrophages and iCAFs were also found in high levels in IM, as opposed to MO. The difference of infiltration level and Radscore between two nodules in IM was relatively small. Furthermore, we developed Radscore for predicting MVI and HCC prognostication that were also able to predict the level of infiltration of APOE + macrophages and iCAFs. Conclusion This study demonstrated the interactions of cell subpopulations and distinct metabolism profiles in MVI + HCC. Besides, MVI prediction Radscore and MVI prognostic Radscore were highly correlated with the infiltration of APOE + macrophages and iCAFs, which helped to understand the biological significance of radiomics and optimize treatment strategy for MVI + HCC.
Objective:To observe the curative efficacy of Baoshen tablet (BST) in treating chronic renal failure(CRF) with deficiency of both Qi and Yin and damp pathogen syndrome (DQYDS).Method: The randomized, double blind,double imitated and controlled trial was used.22 cases in treatment group were treated with BST and imitated tablet,and 24 cases in control group with Shenkangning tablet and imitated tablet.ThechangesofthecumulativescoresoftraditionalChinesemedicine(TCM )syndrome ,thelevelsofserumcreatinine (SCr)andcreatinineclearancerate(CCR)beforeandaftertreatmentinbothgroupswereobserved .Result:The totaleffectiveratewas 86 .4 %intreatmentgroup ,but 70 .0 %incontrolgroup .ThescoresofTCMsyndrome andthelevelsofSCrwerebothsignificantlydecreased (P 0 .0 5orP 0 .0 1)intwogroups ,CCRwassignifi cantlyincreased ,meanwhiletheindexesintreatmentgroupweremoresignificantlyimprovedthanthoseincon trolgroup(P 0 .0 5orP 0 .0 1) .Conclusion :BSTcanmarkedlyimprovetheclinicalmanifestationsofCRF withDQYDS ,decreasethelevelsofSCr ,butincreaseCCR .
Abstract Background: Glioblastoma multiforme (GBM) is the most common and lethal primary human brain tumor and exhibits multiple molecular aberrations. In this study, we attempted to explore the role of a nuclear transport receptor RanBP17 in carcinogenesis and its underlying mechanisms in GBM. Methods: The relevant information retrieved from the Human Integrated Protein Expression Database (HIPED), TCGA, and Rembrandt was analyzed to evaluate and compare RanBP17 expression in various tissues and cancer types. Next U87 and U251 were used to investigate the effects of RPS15A on epithelial-mesenchymal transition (EMT) and malignant behaviors of glioma cells. Further, RPS15A-associated signaling pathways were screened based on the data from the Kyoto Encyclopedia of Genes and Genomes (KEGG) database and verified by using RT-PCR and Western blot (WB) assays. Results: RanBP17 was highly expressed in normal brain tissue, and loss or downregulation of RanBP17 was observed in GBM tissue (83/105, 79.05%) and associated with worse survival of patients. Overexpression of RanBP17 suppressed proliferation, migration and invasion of GBM cells in vitro and remarkably inhibited tumor growth in vivo. In addition, RanBP17 silencing promoted EMT of glioma cells via activating the expression of transcriptional factor Snail. Further experiments confirmed that RanBP17 overexpression promoted the export of β-catenin from cell nuclei and retarded wnt/β-catenin signaling. Conversely, knockdown of RanBP17 gene resulted in accumulation of β-catenin in glioblastoma cell nuclei, which, in turn, promoted expression of EMT-related proteins and malignant progression of glioblastoma by combining other transcript genes. Conclusions: RanBP17 expression is significantly lower in GBM compared to normal brain tissue. Silencing RanBP17 accelerates the EMT process and malignant progression of glioblastoma due to the suppressed export of β-catenin from glioblastoma cell nuclei and the resulting inhibition of wnt/β-catenin signaling. Therefore, loss or downregulation of RanBP17 can be considered a negative prognostic factor for survival of GBM patients. Citation Format: Yi Wang, Penyi Guo, Xiaozai Xie, Sina Zhang, Haitao Yu, Lijun Wu, Ziyan Chen, Gang Chen. RanBP17 retards the epithelial-mesenchymal transition (EMT) and malignant progression of glioblastoma cells by regulating the exportation of beta-catenin from cell nucleus [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2482.
OBJECTIVE To observe morphological characteristics of retina and Bruch’s membrane in apolipoprotein E-deficiency(ApoE-/-) mice with dyslipidemia.METHODS Twenty-four apolipoprotein E deficiency(ApoE-/-) mice at two-month age were randomly divided into high fat diet group and normal diet group,and 12 C57BL mice were chosen as normal diet control group.After being fed for 4 months,total plasma cholesterol(TC) and low density lipoprotein(LDL) were determined,morphological characteristics of retina and Bruch’s membrane were observed under light and electron microscope,and amounts of retinal photoreceptor cells and pigment epithelial cells(RPE) were examined by semi-quantitative histopathology.RESULTS Compared with normal diet control group,TC and LDL were significantly increased in high fat diet group(P 0.001).Under light microscope,retinal photoreceptor cells were disorganized,atrophic and reduced in high fat diet group(P 0.001),and changes of disturbance,randomly oriented fiber and thickening could be seen in Bruch’s membrane(P 0.001),in addition,retinal drusen were formed in partial mice.Under electron microscope,shortening and destruction in basal infolding of basement membrane,swelling of mitochondria,and vacuoles could be observed in RPE,as well as thickening of Brunch membrane with decrease in fiber and rupture in elastin layers.CONCLUSIONS Morphological changes in retina and Bruch’s membrane of ApoE-/-mice with dyslipidemia were in accordance with age-related macular degeneration;therefore,it could be adapted to research age-related macular degeneration.
To investigate the significance of MR features based on the Liver Imaging Reporting and Data System (LI-RADS ver. 2018) for identifying the expression of cytokeratin 19 (CK-19) in patients with combined hepatocellular carcinoma-cholangiocarcinoma (cHCC-CCA) before surgery.The study enrolled 174 patients pathologically confirmed to have cHCC-CCA according to the 2019 WHO classification. The preoperative MR imaging features and clinicopathological findings were retrospectively evaluated and compared between the CK-19-positive and CK-19-negative cHCC-CCA groups.One hundred seventy-four patients (mean age, males vs females: 56.6 ± 10.0 years vs 54.7 ± 14.2 years) were evaluated. The presence of mosaic architecture, targetoid appearance, cholangiectasis, hepatic capsule retraction, and corona enhancement was significantly higher in the CK-19-positive group (all p < 0.05), while nonrim arterial phase hyperenhancement (APHE) was more common in the CK-19-negative group (p = 0.04). The univariate analysis showed that hepatitis B virus infection, CEA > 5 ng/mL, tumor size, nonrim APHE, mosaic architecture, targetoid appearance, cholangiectasis, hepatic capsule retraction, and corona enhancement were significant risk factors for CK-19-positive cHCC-CCA (all p < 0.05). Unfortunately, the multivariate analysis revealed that only corona enhancement (OR = 2.359, p = 0.03) was an independent risk factor associated with CK-19-positive cHCC-CCA.Corona enhancement is significantly correlated with CK-19 positivity in patients with cHCC-CCA.
To investigate the effect of small interference RNA (siRNA) on mdr1 and P-glyco-protein (P-gp) expression of multi-drug resistance (MDR) human leukemia cell line K562/A02.Three si RNAs (si-mdr1-1, si-mdr1-2, si-mdr1-3) which were specifically targeted mdr1 gene were synthesized and transfected into K562/A02 cells. Expression of mdr1 mRNA was assayed by RT-PCR. P-gp expression and intracellular daunorubicin (DNR) concentration were determined by flow cytometry. 50% inhibition concentration (IC(50)) of doxorubicin (ADM) on K562/A02 was determined by MTT method.Treatment of K562/A02 cell with the 3 kinds of siRNAs resulted in a reversal of MDR of a different extent. The third siRNA was more effective in the suppression of mdr1 with a significant reduction of (58.0 +/- 1.54)% of the mdr1 mRNA expression. Positive expression rate of p170 decreased from (76.0 +/- 1.0)% to (19.6 +/- 1.9)%, and the relative efficiency of K562/A02 to ADM was 70.4%. The intracellular accumulation of DNR increased after siRNA treatment.The siRNA could effectively restore the sensitivity of K562/A02 cells to conventional chemotherapeutic agents.
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