Undifferentiated embryonal sarcoma of the liver in children: our experience in four difficult cases and three-dimensional practical exploration.

AIMS: To explore rare and difficult cases of undifferentiated embryonal sarcoma of the liver (UESL) in children in a single centre, summarize the diagnosis and treatment experience and analyse the role of a computer-assisted surgery system (Hisense CAS), thus providing a new global vision and three-dimensional perspective. METHODS: We retrospectively collected the clinical data including the diagnoses and treatment processes, of children with UESL confirmed by histopathological examination in our hospital from January 2009 to December 2020. The relationship between the tumour volume and important blood vessels and between the liver volume and tumour volume, as well as other three-dimensional characteristics in the reconstructed three-dimensional model were analysed using Hisense CAS. The findings from this analysis can be used to aid in surgical decision-making and preoperative planning. RESULTS: Four children-3 girls and 1 boy-with UESL were included in the study. The age at onset ranged from 6 to 8 years. All four children presented with symptoms of abdominal discomfort, and abdominal masses were detected during physical examination. Owing to the wishes of their parents and the possibility that the disease was benign, all four children underwent one-stage radical surgery. For patient 1, a three-dimensional reconstruction was created during the initial diagnosis, which made accurate evaluation and planning of the preoperative procedure challenging. In patient 2, the tumour was located in the middle lobe of the liver and involved the first and second hepatic hilum. For patient 3, the pathological diagnosis of the tumour after surgery was challenging, but eventually, the diagnosis was confirmed through histochemistry and consultation with higher-level hospitals. Patient 4 had a giant tumour, which had a preoperative simulated future liver remnant volume (FLV) that was 21.0% of the total volume of the liver and tumour (TLTV). According to the standard liver volume (SLV) for children, the FLV was 77.0% of the SLV, making surgery feasible. All four children underwent complete resection, and only patient 4 experienced recurrence below the diaphragm 19 months after surgery. Currently, the 3-year overall survival rate is 100%, and the 3-year event-free survival rate is 75%. CONCLUSION: UESL in children is rare, and the key to diagnosis and treatment is complete surgical resection. Through individualized three-dimensional surgical planning, accurate and complete resection of difficult and complex UESL in children can be achieved, leading to a favourable prognosis.

BCL2L1 is regulated by the lncRNA MIR4435-2HG-miR-513a-5p-BCL2L1 ceRNA axis and serves as a biomarker for pancreatic adenocarcinoma treatment and prognosis.

Pancreatic adenocarcinoma (PAAD) is one of the most malignant cancers. After escaping death, cancer cells are made more metastatic, aggressive, and also drug-resistant through anoikis resistance. The aim of this study is to explore the molecular mechanisms of anoikis-related genes in PAAD and to identify potential key biomarkers. We integrated information about PAAD from The Cancer Genome Atlas (TCGA) and The Genotype-Tissue Expression (GTEx) databases and identified anoikis-related gene BCL2L1 by survival analysis, univariate Cox regression analysis, and multifactorial Cox regression analysis. Various bioinformatics approaches showed that BCL2L1 was a valuable prognostic marker that might be involved in PAAD development and progression through different mechanisms, including cancer intervention, genomic heterogeneity, and RNA modifications. Our analysis showed that BCL2L1 expression also closely correlates with the expression of various immune checkpoint inhibitors. In particular, we found that long non-coding RNA MIR4435-2HG acted as ceRNA sponging miR-513a-5p to promote the expression of BCL2L1, thereby promoting pancreatic cancer cells proliferation. In conclusion, BCL2L1 expression regulated by the MIR4435-2HG-miR-513a-5p-BCL2L1 ceRNA axis might be used as a biomarker for cancer prognosis, treatment selection, and follow-up in PAAD patients.

A pan-cancer analysis to determine the prognostic analysis and immune infiltration of HSPA5.

BACKGROUND: Heat shock 70kDa protein 5 (HSPA5), also known as GRP78, is widely expressed in most malignant cells and has been shown to have a significant role in the spread of most malignancies by transferring them to the cell membrane. High-level HSPA5 may serve as an independent prognostic marker for various malignancies due to its ability to accelerate tumor growth and migration, inhibit cell apoptosis and closely connect to prognosis. Therefore, it is crucial to examine HSPA5 using pan-cancer research, which might result in the discovery of novel cancer treatment targets. METHOD: The GTEx and TCGA databases have both provided evidence of the expression of various amounts of HSPA5 in various tissues. The Clinical Proteomics Tumor Analysis Consortium (CPTAC) evaluated the levels of HSPA5 protein expression, while qPCR investigations also evaluated the expression of HSPA5 mRNA in certain tumors. HSPA5 was studied using the Kaplan-Meier method to examine how it influences overall survival and disease-free survival in malignancies. GEPIA2 was used to investigate the correlation between HSPA5 expression and the clinical stage of cancer. The tumor-immune system interaction database (TISIDB) examined the expression of HSPA5 in association with molecular and tumor immune subtypes. The co-expressed genes of HSPA5 were extracted from the STRING database, and the top 5 co-expressed genes of HSPA5 in 33 cancers were identified using the TIMER database. Further research examined the relationship between tumor mutations and HSPA5. Microsatellite Instability (MSI) and Tumor Mutation Burden (TMB) were the primary areas of interest. The association between HSPA5 mRNA expression and immune infiltration was also explored using the TIMER database. Additionally, through the Linkedomics database, we examined the enrichment of GO and KEGG for HSPA5 in glioblastoma. Finally, the Cluster Analyzer tool was used to carry out a GSEA functional enrichment investigation. RESULTS: HSPA5 mRNA expression was found to be greater in all 23 tumor tissues than in the equivalent normal tissues, and high HSPA5 expression appeared to be strongly related to a poor prognosis in the majority of cancers, as observed by survival plots. In the tumour clinical stage display map, HSPA5 showed differential expression in most tumours. HSPA5 is strongly associated with Tumor Mutation Burden (TMB) and Microsatellite Instability (MSI). Cancer-associated Fibroblasts (CAFs) infiltration was strongly associated with HSPA5, as were nine immunological subtypes of malignancy and seven molecular subtypes of malignancy. According to the results of GO and KEGG enrichment analyses, HSPA5 in GBM is mostly involved in neutrophil-mediated immunological and collagen metabolic activities. Additionally, GSEA enrichment analyses of HSPA5 and associated genes demonstrated a substantial link between HSPA5 and the immunological milieu of tumors, cell division and nervous system regulation. By using qPCR, we were able to further corroborate the enhanced expression in the GBM, COAD, LUAD and CESC cell lines. CONCLUSION: Our bioinformatics research leads us to hypothesize that HSPA5 may be involved in immune infiltration as well as tumor growth and progression. Additionally, it was found that differentially expressed HSPA5 is linked to a poor prognosis for cancer, with the neurological system, the tumor immunological microenvironment and cytokinesis being potential contributing factors. As a result, HSPA5 mRNA and the associated protein might be used as therapeutic targets and possible prognostic markers for a range of malignancies.

Electrochemical dual signal sensing platform for the simultaneous determination of dopamine, uric acid and glucose based on copper and cerium bimetallic carbon nanocomposites.

A highly sensitive electrochemical sensor for the simultaneous dual signal determination of dopamine (DA), uric acid (UA) and glucose (Glu) has been obtained using nanocomposites based on the copper and cerium bimetallic nanoparticles and carbon nanomaterials of graphene and single-walled carbon nanotubes in the presence of Tween 20 (GR-SWCNT-Ce-Cu-Tween 20) modified glassy carbon electrode. The surface morphology of the nanocomposites was characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD), and the electrochemical behavior of the sensor was investigated by cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) with potassium ferricyanide as probe. In the coexistence system of DA, UA and Glu, three clear and well-isolated voltammetric peaks were obtained by CV and differential pulse voltammetry (DPV), and oxidation peak currents of DA and UA are positively correlated with their concentrations respectively, while the peak current of Glu is negatively correlated with its concentration. Linearity was obtained in the ranges of 0.1-100 µM for dopamine, 0.08-100 µM for uric acid and 1-1000 µM for glucose with DPV, and the detection limits (S/N = 3) of 0.0072 µM, 0.0063 µM, and 0.095 µM for DA, UA and Glu, respectively. The method was successfully applied to the determination of DA, UA and Glu in blood serum samples, which provided a reference for further sensor research.

Bone Marrow Mesenchymal Stem Cells-Derived Extracellular Vesicles Promote Proliferation, Invasion and Migration of Osteosarcoma Cells via the lncRNA MALAT1/miR-143/NRSN2/Wnt/ß-Catenin Axis.

INTRODUCTION: Osteosarcoma is a malignant primary bone tumor. Bone marrow-derived mesenchymal stem cells-derived extracellular vesicles (BMSC-EVs) bear repair function for bone and cartilage. This study investigated the mechanism of BMSC-EVs in osteosarcoma cell proliferation, migration and invasion. METHODS: BMSC-EVs were isolated and identified. The effects of different concentrations of EVs on osteosarcoma cell proliferation, migration and invasion were evaluated. LncRNA MALAT1 expression in osteosarcoma cells was detected. BMSCs were transfected with si-MALAT1 or si-NC. The binding relationships between MALAT1 and miR-143, and miR-143 and NRSN2 were verified. Levels of NRSN2 and Wnt/ß-catenin pathway key proteins were detected. miR-143 mimic was transfected into EVs-treated osteosarcoma cells. Nude mice were injected with MG63 cells to verify the effect of EVs on osteosarcoma growth in vivo. RESULTS: BMSC-EVs facilitated proliferation, invasion and migration of osteosarcoma cells. BMSC-EVs carried MALAT1 into osteosarcoma cells. BMSC-EVs-treated osteosarcoma cells showed increased MALAT1 and NRSN2 expressions, decreased miR-143 expression, and activated Wnt/ß-catenin pathway. miR-143 mimic or si-MALAT1 reversed the effects of BMSC-EVs on osteosarcoma cells. In vivo experiment confirmed that BMSC-EVs promoted tumor growth in nude mice. DISCUSSION: BMSC-EVs promoted proliferation, invasion and migration of osteosarcoma cells via the MALAT1/miR-143/NRSN2/Wnt/ß-catenin axis. This study might offer new insights into osteosarcoma management.

A functional ratio fluorescence sensor platform based on the graphene/Mn-ZnS quantum dots loaded with molecularly imprinted polymer for selective and visual detection sinapic acid.

A functional ratio fluorescence sensor based on the molecularly imprinted polymer (MIP) coated double quantum dots (QDs) being composited of Mn-ZnS QDs and silica-coated graphene quantum dots (GQDs@SiO2) had been established for the sensitive, selective and visual detection of sinapic acid (SA). MIPs@Mn-ZnS/GQDs@SiO2 was synthesized through a simple one-pot sol-gel reaction, and it exhibited two fluorescence emission peaks with yellow fluorescence of Mn-ZnS QDs at 580 nm and the blue fluorescence of GQDs at 445 nm. SA can selectively enhance the fluorescence of GQDs but quench the Mn-ZnS QDs fluorescence to the MIPs@Mn-ZnS/GQDs@SiO2. The ratio of fluorescence enhancement to fluorescence reduction is linear with the concentration of SA from 9 to 81 nM with the detection limits of 0.8388 nM (S/N = 3). And the constructed fluorescent probe can also be used to visually detect SA according to the change of color. More importantly, molecular imprinting technique enables the sensors to selectively recognize the SA while other similar structure molecules hardly interfere with the SA determination in the measurement environment. Meanwhile, the fluorescence sensors have the advantages of fast response time and long duration of fluorescence intensity. These excellent performances made the proposed method to be applied for the determination of SA in Semen Sinapis and Descurainiae Semen.

Effect of aerobic exercise combined with ginkgo polysaccharide on weight, blood glucose and glycosylated serum protein in diabetic rats.

Streptozotocin copied diabetic rats model were studied through aerobic exercise combined with ginkgo polysaccharide. Aimed to offering the updating experimental basis to prevent diabetic through aerobic exercise combined with ginkgo polysaccharide, the effect of aerobic exercise combined with ginkgo polysaccharide were discussed on the weight, blood glucose, glucosylated serum protein and the secretion ability of islet ß cells, oral glucose tolerance test, islet cell pathological morophological changes and positive expression of Bax and Bcl-2. At the end of the experiment, the parameters changes were detected, which were body weight, weight of pancreas islet, Fasting blood glucose(FGB), glycosylated serum protein(GSP), FINS, C-peptide, glucose kinase (GK), ultramicro total atpase, ultramicro Na+K+-atpase, altramicro Ca2-M2+-atpase, ß cell function index (HBCI), and oral glucose tolerance test (OGTT). HE dyeing technology was applied on insulin for pathological morphology observation. The positive expression changes of islet ß cells Bcl-2 and Bax were detected by immunohistochemical staining and semi-quantitative method of stereology. Experimental results proved that body weight, GK, ultra micro Na+K+-atpase, ultra micro Ca2-M2+-atpase, C peptide were significantly increased after the intervention of ginkgo polysaccharide (P<0.05), correspondingly, insulin levels were dramatic increased (P<0.01), while blood glucose and GSP were decreased significantly (P<0.05), the ultramicro total atpase decrease, without statistically significance. After the exercise intervention, body weight, ultra micro Na+K+-atpase, ultra micro Ca2-M2+-atpase, C peptide significantly increased (P<0.05), insulin level apparently increased (P<0.01), blood glucose and GSP dramatically decreased (P<0.05), GK and ultra micro total atpase had an elevated trend, while without statistically significance. After the rational exercise combined with ginkgo polysaccharide intervention, GK, ultra micro total atpase, ultra micro Na+K+-atpase, ultra micro Ca2-M2+-atpase and insulin level significantly increased (P<0.05), body weight and c peptide significantly increased (P<0.01), blood glucose and GSP obviously decreased (P<0.01). The pathological changes of insulin in diabetic rats were improved. The increased ratio of Bcl-2/Bax enabled the pancreatic ß cell developed in the direction of repair and regeneration. The combination of aerobic exercise and ginkgo polysaccharide could help to increase insulin secretion in diabetic rats, and increase insulin reserve and secretion capacity. Then it can control the weight boss of diabetic rats, along with the blood glucose. So it could lead to the development of the pancreas islets of diabetic rats in the direction of repair and regeneration.