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In this paper, a novel multitask healthcare management recommendation system leveraging the knowledge graph is proposed, which is based on deep neural network and 5G network, and it can be applied in mobile and terminal device to free up medical resources and provide treatment programs. The technique we applied is referred to as KG-based recommendation system. When several experiments have been carried out, it is demonstrated that it is more intelligent and precise in disease prediction and treatment recommendation, similar to the state of the art. Also, it works well in the accuracy and comprehension, which is much higher and highly consistent with the predictions of the theoretical model. The fact that our work involves studies of multitask healthcare management recommendation system, which can contribute to the smart healthcare development, proves to be promising and encouraging.

The effects of hydrogen-rich water on oxidative stress via the Nrf2/ARE signaling pathway were studied in rats with myocardial ischemia-reperfusion injury (MIRI). Sixty rats were randomly divided into a hydrogen-rich water group and a control group, with 30 rats in each group. The two groups were randomly divided into three groups: pre-ischemic period, ischemic period and reperfusion period. After the heart was removed, it was fixed in a Langendorff device and perfused with an oxygen-balanced 37 °C perfusate. The control group was perfused with Kreb’s-Ringers (K-R) solution, and the hydrogen-rich water group was perfused with K-R solution + hydrogen-rich water. The levels of mRNA and protein of Nrf2, NQO1, HO-1 and SOD-1 in cardiomyocytes were detected by RT-qPCR, immunohistochemistry (IHC) and Western blot analysis. SOD activity and MDA content were determined. Hydrogen-rich water increased the activation of the Nrf2/ARE signaling pathway, and the levels of mRNA and protein Nrf2, NQO1, HO-1 and SOD-1 were significantly increased (P

Background Pre-eclampsia is a common pregnancy complication, affecting 5–8% of pregnancies worldwide. The specific mechanism of pre-eclampsia remains unclear. Objective In this study, we aimed to apply bioinformatics approach to reveal related pathways or genes involving in the development of pre-eclampsia. Study design The gene expression profiles of GSE9984 and GSE4707 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes analysis was performed by GEO2R. The Database for Annotation, Visualization and Integrated Discovery (DAVID) was applied to analyze the functional enrichment, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway of the differentially expressed genes. Gene Set Enrichment Analysis (GSEA) was conducted using the software GSEA v3.0. Protein-protein interaction (PPI) relationships were evaluated by the Search Tool for the Retrieval of Interacting Genes (STRING) and network visualization was constructed by the Cytoscape. Cell count kits-8 (CCK-8), transwell migration assay and tube formation assay were performed. Results A total of 160 common differentially expressed genes were extracted. Transforming growth factor (TGF) beta signaling pathway was shown to be notable in the development of pre-eclampsia. ENG, a key gene of TGF-β signaling pathway, inhibited the proliferation, migration and invasion of both HTR-8/SVneo cells and human umbilical vein endothelial cells (HUVECs), and additionally suppressed the capillary formation of HUVECs. Conclusion Bioinformatics approach combined with cell experiments in this study revealed that TGF-β signaling pathway was critical for the development of pre-eclampsia, and efficient biomarkers underlying this pathway need to be further investigated.

This research systematically profiled the global N6‐methyladenosine modification pattern of circular RNAs (circRNAs) in glioblastoma (GBM). Based on RNA methylation sequencing (MeRIP sequencing or N6‐methyladenosine sequencing) and RNA sequencing, we described the N6‐methyladenosine modification status and gene expression of circRNAs in GBM and normal brain tissues. N6‐methyladenosine–related circRNAs were immunoprecipitated and validated by real‐time quantitative PCR. Bioinformatics analysis and related screening were carried out. Compared with those of the NC group, the circRNAs from GBM exhibited 1370 new N6‐methyladenosine peaks and 1322 missing N6‐methyladenosine peaks. Among the loci associated with altered N6‐methyladenosine peaks, 1298 were up‐regulated and 1905 were down‐regulated. The N6‐methyladenosine level tended to be positively correlated with circRNA expression. Bioinformatics analysis was used to predict the biological function of N6‐methyladenosine–modified circRNAs and the corresponding signalling pathways. In addition, through PCR validation combined with clinical data mining, we identified five molecules of interest (BUB1, C1S, DTHD1, F13A1 and NDC80) that could be initial candidates for further study of the function and mechanism of N6‐methyladenosine–mediated GBM development. In conclusion, our findings demonstrated the N6‐methyladenosine modification pattern of circRNAs in human GBM, revealing the possible roles of N6‐methyladenosine–mediated novel noncoding RNAs in the origin and progression of GBM.

The chemical modification of RNA is a newly discovered epigenetic regulation mechanism in cells and plays a crucial role in a variety of biological processes. N6-methyladenine (m6A) mRNA modification is the most abundant form of posttranscriptional RNA modification in eukaryotes. Through the development of m6A RNA sequencing, the relevant molecular mechanism of m6A modification has gradually been revealed. It has been found that the effect of m6A modification on RNA metabolism involves processing, nuclear export, translation and even decay. As the most common malignant tumour of the central nervous system, gliomas (especially glioblastoma) have a very poor prognosis, and treatment efficacy is not ideal even with the application of high-intensity treatment measures of surgery combined with chemoradiotherapy. Exploring the origin and development mechanisms of tumour cells from the perspective of tumour biogenesis has always been a hotspot in the field of glioma research. Emerging evidence suggests that m6A modification can play a key role in gliomas through a variety of mechanisms, providing more possibilities for early diagnosis and targeted therapy of gliomas. The aim of the present review is to focus on the research progress regarding the association between m6A modification and gliomas. And to provide a theoretical basis according to the currently available literature for further exploring this association. This review may provide new insights for the molecular mechanism, early diagnosis, histologic grading, targeted therapy and prognostic evaluation of gliomas.

Introduction To date, we have only an incomplete understanding of how gene expression in the human placenta changes at the genome-wide scale from very early in gestation to term. Our aim was to investigate the dynamic changes in gene expression throughout placentation. Methods In our study, gene expression profiles were collected of human placentas from 4 to 40 gestational weeks of age. Simple linear regression and weighted correlation network analysis were applied to identify genes of interest. Analyses of gene enrichment, including gene ontology and pathways from the Kyoto Encyclopedia of Genes and Genomes, were performed using clusterProfiler. Finally, dynamic changes in the expression of individual genes were represented using line graphs of scaled and adjusted gene expression. Results Our results highlighted a total of 5173 genes that are involved in different periods of placentation. Downstream annotation of these genes revealed the biological processes and pathways involved, from which we chose to further investigate the PPAR signaling pathway. We were able to detect changes over time in many genes involved in lipid storage/metabolism, including members of the FABP family and LPL. These patterns were corroborated by lipid staining of placental sections, which revealed a significant decrease in lipid droplet content in placentas from early in the first trimester to term. Conclusion Our study provides detailed information on the dynamics of biological processes and pathways across human placentation. These findings give us new clues for deciphering the normal functions of placentation and the ways in which the mis-regulation of these pathways may be linked to pregnancy-related diseases. As an example, our results show that the PPAR signaling pathway mediates a constant decrease in placental lipid content over the course of pregnancy.

Since early December 2019, a number of pneumonia cases associated with unknown coronavirus infection were identified in Wuhan, China, and many additional cases were identified in other regions of China and in other countries within 3 months. Currently, more than 80,000 cases have been diagnosed in China, including more than 3000 deaths. The epidemic is spreading to the rest of the world, posing a grave challenge to prevention and control. On February 12, 2020, the International Committee on Taxonomy of Viruses and the World Health Organization officially named the novel coronavirus and associated pneumonia as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19), respectively. According to the recent research on SARS-CoV-2, the virus mainly infects the respiratory system but may cause damage to other systems. In this paper, we will systematically review the pathogenic features, transmission routes, and infection mechanisms of SARS-CoV-2, as well as any adverse effects on the digestive system, urogenital system, central nervous system, and circulatory system, in order to provide a theoretical and clinical basis for the diagnosis, classification, treatment, and prognosis assessment of SARS-CoV-2 infection.

Glioma is the most common primary tumour of the central nervous system, and is associated with a high postoperative recurrence rate and resistance to chemotherapy. High‑grade glioblastoma in particular has a very poor prognosis and poses a serious threat to human health. Related studies have confirmed that the occurrence and development of gliomas are closely associated with the abnormal expression and regulation of genes. Moreover, the number of studies on the association of the expression of non‑coding RNAs [linear RNAs, microRNAs and circular RNAs (circRNAs)] in human cells with glioma has been gradually increasing in recent years. Among those, circRNAs, previously considered to be 'splicing errors', have been shown to be highly expressed in eukaryotic cells and regulate the biological behaviour of gliomas. circRNAs are highly abundant and stable, and have become a research hotspot in the field of glioma molecular biology. The aim of the present review was to focus on the research progress regarding the association between circRNA expression and gliomas, and to provide a theoretical basis according to the currently available literature for further exploring this association. The present study may be of value for the early diagnosis, pathological grading, targeted therapy and prognostic evaluation of gliomas.

BACKGROUND Lon protease is responsible for degrading proteins injured by oxidation, and has 2 isoforms, located in mitochondria and peroxisomes. Recent research showed that Lon protease was upregulated in different types of human cancer, but the role of Lon peptidase 2, peroxisomal (LONP2) in cancer is not well understood. It is known, however, that in cancer biology, reduction-oxidation is one of the molecular mechanisms involved in tumorigenesis. MATERIAL AND METHODS Oncomine databases and tissue microarrays, initially using immunohistochemistry, were used to analyze LONP2 expression in cervical cancer. In order to uncover the biologic functions and mechanism(s) underlying LONP2 in cervical tumorigenesis, we downregulated the expression of LONP2 using 2 siRNAs transduced in HeLa and SiHa cells. CCK8 assays were performed to evaluate cell viability. Cell cycle and apoptosis assays were used to determine cell growth. Cell migration and invasion assays were used to study changes in cell migration and invasion capacity. Immunofluorescence and flow cytometry were performed to analyze the changes in ROS production. RESULTS We found that the expression of LONP2 was significantly upregulated in cervical cancer, and there was a significant association with pathology type, pathology grade, and clinical stage, but not with age or lymph node metastasis. Moreover, we demonstrated that knocking down LONP2 in HeLa and SiHa cells reduced cell proliferation, cell cycle, apoptosis, migration, invasion, and oxidative stress levels. CONCLUSIONS Our findings suggest that LONP2 promotes cervical tumorigenesis via oxidative stress and may be a potential biomarker and therapeutic target in cervical cancer.

Cardiovascular disease accounts for one-third of all deaths, with ischemic heart disease as the main cause of death. Under pathological conditions, ischemia-reperfusion injury (IRI) often occurs in tissues. Ischemic injury is mainly caused by anaerobic cell death and reperfusion which results in a wide range of inflammatory responses. These responses are able to increase tissue damage and even damage to the whole body. IRI can also aggravate the original cardiovascular disease during the treatment of cardiovascular disease. Therefore, it is particularly important to understand the mechanism of myocardial ischemia-reperfusion injury (MIRI) for clinical treatment and application. At the same time, it is necessary to find a safe, reliable and feasible method for treating MIRI to reduce the incidence of complications and mortality as well as improve the prognosis and quality of life of patients. As a selective antioxidant, hydrogen can neutralize excessive free radicals, has certain anti-apoptotic and anti-inflammatory effects and it has gradually become a focus and hotspot of preclinical and clinical research. Hydrogen has been shown to have a certain therapeutic effect on MIRI, which can provide a new therapeutic direction for the clinical treatment of myocardial ischemia-reperfusion injury. In this review, the protective mechanism and clinical application of hydrogen in myocardial ischemia-reperfusion injury is discussed.

Physiological oxygen tension rises dramatically in the placenta between 8 and 14 weeks of gestation. Abnormalities in this period can lead to gestational diseases, whose underlying mechanisms remain unclear. We explored the changes at mRNA level by comparing the transcriptomes of human placentas at 8–10 gestational weeks and 12–14 gestational weeks. A total of 20 samples were collected and divided equally into four groups based on sex and age. Cytotrophoblasts were isolated and sequenced using RNAseq. Key genes were identified using two different methods: DESeq2 and weighted gene co-expression network analysis (WGCNA). We also constructed a local database of known targets of hypoxia-inducible factor (HIF) subunits, alpha and beta, to investigate expression patterns likely linked with changes in oxygen. Patterns of gene enrichment in and among the four groups were analyzed based on annotations of gene ontology (GO) and KEGG pathways. We characterized the similarities and differences between the enrichment patterns revealed by the two methods and the two conditions (age and sex), as well as those associated with HIF targets. Our results provide a broad perspective of the processes that are active in cytotrophoblasts during the rise in physiological oxygen, which should benefit efforts to discover possible drug-targeted genes or pathways in the human placenta.

Interleukin‑17A (IL‑17A) is a CD4 T-cell-derived pro-inflammatory cytokine that is involved in human cervical tumorigenesis. Heparanase (HPSE) is an endo-glycosidase expressed in mammals, which has been confirmed to be associated with cervical cancer invasion. In the present study, it was hypothesized that IL‑17A and HPSE are key proteins promoting tumor angiogenesis and cell proliferation and invasion in cervical cancer. The expression of IL‑17A and HPSE in cervical cancer tissues was detected by immunohistochemical staining. In addition, the expression of IL‑17A and HPSE was down- and upregulated via RNAi and human recombinant proteins, and MTT and Transwell assays were performed to examine cervical cancer cell proliferation and invasion, respectively. Flow cytometry analysis was also performed to detect cell cycle distribution, and the levels of target mRNA and protein were evaluated by reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. IL‑17A and HPSE were highly expressed in cervical cancer tissues, and microvessel density was notably higher in the IL‑17A-positive group. IL‑17A and/or HPSE recombinant protein promoted the proliferation and invasion of cervical cancer cells, increased the proportion of cells in the G2/M phase, and enhanced the mRNA and protein expression of human papillomavirus E6, P53, vascular endothelial growth factor and CD31, whereas downregulation of IL‑17A and/or HPSE exerted the opposite effects. Furthermore, downregulation of IL‑17A and/or HPSE was found to inhibit the expression of nuclear factor (NF)-κB P65. In summary, IL‑17A and HPSE may promote tumor angiogenesis and cell proliferation and invasion in cervical cancer, possibly via the NF-κB signaling pathway. These findings may lead to the identification of new diagnostic markers and therapeutic targets.

Pre-eclampsia (PE) is a common but complex condition that can occur in pregnancy. It is estimated to affect 3-8% of pregnancies worldwide. PE development is thought to be multifactorial and to involve the dysregulation of microRNA (miR) expression. However, the precise mechanisms of PE development remain unclear. The present study aimed to illustrate the association between miR‑203 expression and PE development in samples of human placenta collected from mothers with (n=18) and without (n=20) PE. It was demonstrated that miR‑203 expression was significantly increased in the PE placenta compared with the normal placenta samples, while the expression of vascular endothelial growth factor A (VEGFA) was decreased. In vitro experiments revealed that miR‑203 overexpression significantly downregulated VEGFA expression and inhibited the proliferation, migration and invasion ability of HTR‑8/SVneo cells. Suppression of miR‑203 expression alleviated these effects. A luciferase reporter assay confirmed the interaction of the 3'‑untranslated region of VEGFA with miR‑203. Thus, miR‑203 may have significant contribution to the development of PE by targeting VEGFA in the human placenta and may have potential as a biomarker or therapeutic target in the treatment of PE.

Impaired placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) activity which inactivates maternal glucocorticoids is associated with poor fetal growth and a higher risk of chronic diseases in adulthood. This study aimed to elucidate the epigenetically regulatory mechanism of nicotine on placental 11β-HSD2 expression. Pregnant Wistar rats were administered 1.0 mg/kg nicotine subcutaneously twice a day from gestational day 9 to 20. The results showed that prenatal nicotine exposure increased corticosterone levels in the placenta and fetal serum, disrupted placental morphology and endocrine function, and reduced fetal bodyweight. Meanwhile, histone modification abnormalities (decreased acetylation and increased di-methylation of histone 3 Lysine 9) on the HSD11B2 promoter and lower-expression of 11β-HSD2 were observed. Furthermore, the expression of nicotinic acetylcholine receptor (nAChR) α4/β2, the phosphorylation of extracellular regulated kinase 1/2 (ERK1/2) and Ets-like protein-1 (Elk-1), and the expression of early growth response-1 (Egr-1) were increased in the nicotine groups. In human BeWo cells, nicotine decreased 11β-HSD2 expression, increased nAChRα9 expression, and activated ERK1/2/Elk-1/Egr-1 signaling in the concentration (0.1–10 μM)-dependent manner. Antagonism of nAChRs, inhibition of ERK1/2 and Egr-1 knockdown by siRNA were able to block/abrogate the effects of nicotine on histone modification and expression of 11β-HSD2. Taken together, nicotine can impair placental structure and function, and induce fetal developmental toxicity. The underlying mechanism involves histone modifications and down-regulation of 11β-HSD2 through nAChRs/ERK1/2/Elk-1/Egr-1 signaling, which increases active glucocorticoids levels in the placenta and fetus, and eventually inhibits the fetal development.

Angiogenesis during placentation is of great significance in maintaining normal pregnancy. However, the molecular mechanisms of this process are not clear. It has been reported that miR-203 plays a critical role in the development and progression of many tumors but not focused on the relationship between miR-203 and placental angiogenesis. The present study aims to illustrate the correlation between miR-203 and vascular endothelial growth factor (VEGFA)/vascular endothelial growth factor receptors 2 (VEGFR2) in human placenta and human umbilical vein endothelial cells (HUVECs) obtained from 40 samples. Samples of human placenta were collected based on gestation age, which was divided into early preterm (n = 10), late preterm (n = 12), and term (n = 18). In this work, we demonstrated that the expression of miR-203 decreased significantly in the placenta according to the gestation age, in contrast, the expression of VEGFA and VEGFR2 increased accordingly. In vitro experiments revealed that overexpression of miR-203 not only suppressed the proliferation, migration, invasion, and tube formation of HUVECs but also affected the expression of VEGFA and VEGFR2. Furthermore, inhibition of miR-203 expression showed equally apparent positive effects on HUVECs. In conclusion, our study suggests that miR-203 plays an important role in regulating placental angiogenesis through inhibiting the expression of VEGFA and VEGFR2, thus miR-203 may represent a potential therapeutic target for patients with abnormal formation of blood vessels in the placenta.

HOX transcript antisense RNA (HOTAIR) is a long non-coding RNA located within the Homeobox C (HOXC) gene cluster on chromosome 12. Previous studies have revealed that HOTAIR is overexpressed in many types of cancers and is associated with metastasis and poor survival rates; however, few reports have mentioned the relationship between HOTAIR and angiogenesis of the human placenta. The aim of the present study was to investigate the correlation between HOTAIR and vascular endothelial growth factor (VEGF) A in the human placenta. HOTAIR levels decreased significantly in human placenta with increasing gestational age, and were negatively correlated with VEGFA levels. Invitro assays revealed that HOTAIR overexpression suppressed the proliferation, migration, invasion and tube formation of human umbilical vein endothelial cells (HUVECs); however, inhibition of HOTAIR had the opposite effects. Furthermore, VEGFA overexpression reversed the inhibitory effect of HOTAIR on the proliferation, migration, invasion and tube formation of HUVECs. In addition, overexpression of HOTAIR significantly inhibited VEGFA expression. Notably, a luciferase reporter assay found that HOTAIR inhibited VEGFA transcription by directly targeting the VEGFA promoter. Together, these results suggest that HOTAIR plays an important role in suppressing angiogenesis of the human placenta by inhibiting the expression of VEGFA; thus, HOTAIR may represent a potential therapeutic target for patients with human placental vascularisation abnormalities.

To observe the effect of C-reactive protein (CRP) on the expressions of Notch pathway components in human peripheral blood endothelial progenitor cells (EPC) in vitro.Mononuclear cells isolated by density gradient centrifugation of human peripheral blood mixed with 6% hydroxyethyl starch (Hes) were plated on fibronectin-coated 6-well culture dishes. After 7 days, the adherent cells were cultured in the presence of 10 and 20 mg/L CRP for 48 h, and the proliferation, migration, and adhesion abilities of the cells were observed. The mRNA expressions of Notch-1 and its ligand Jagged-1 in the EPCs were measured by RT-PCR, and their protein expressions by Western blotting.CRP at 10 and 20 mg/L caused a significant reduction in the number of viable EPCs (61∓3 and 54∓3, respectively) as compared with PBS (71∓4, P0.05). CRP also resulted in a significant suppression of the proliferation, migration and adhesion capacities of the EPCs. The mRNA and protein expressions of Jagged-1 and Notch-1 in the EPCs significantly increased following CRP exposure in comparison with PBS treatment.CRP can suppress the proliferation, migration and adhesion capacities of the EPCs probably by affecting the expressions of the Notch-1 pathway components.