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1.
Medicine (Baltimore) ; 100(4): e24484, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530265

RESUMO

BACKGROUND: Ewing sarcoma (ES), the second most prevalent bone malignant tumor has no widely known prognostic biomarker. Earlier studies have suggested that chaperonin containing TCP1 complex 6A (CCT6A), which encodes a molecular protein chaperone, is involved in the pathogenesis of many cancers. However, there are no known reports providing clear evidence of its role in ES pathogenesis. METHODS: We performed a bioinformatic analysis of 32 ES specimens from the GSE17618 dataset concentrating on the differences in gene expression, OS, event-free survival (EFS) in the different subgroups. Immunohistochemical studies were also performed to identify the expression levels of selected genes in ES and immediate paracancerous tissues. RESULTS: After 3 screenings, CCT6A was identified to be highly correlated with ES prognosis. Our survival analysis revealed a low overall survival (OS) for high CCT6A expression (P-value = .024). Our Cox regression analysis identified CCT6A expression, lEFS, and age were strongly associated with prognosis of ES. Our multivariate Cox regression analysis shows that CCT6A (P-value = .015), age (P-value = .026), and EFS (P-value = .002) were independent poor prognostic biomarkers. Our immunohistochemical analysis showed that the expression levels of CCT6A were significantly higher in ES tissues compared to the paracancerous tissues. CONCLUSION: From the results of our study, we identified the expression levels of CCT6A to be strongly associated with prognosis of ES. Thus, the expression levels of the CCT6A gene could serve as a biomarker for the prediction of ES prognosis.


Assuntos
Neoplasias Ósseas/genética , Chaperonina com TCP-1/metabolismo , Sarcoma de Ewing/genética , Adolescente , Fatores Etários , Biomarcadores Tumorais/genética , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Criança , Bases de Dados Genéticas , Feminino , Regulação da Expressão Gênica , Humanos , Masculino , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Sarcoma de Ewing/mortalidade , Sarcoma de Ewing/patologia , Adulto Jovem
2.
Biomed Res Int ; 2021: 8840107, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33575347

RESUMO

The current study is aimed at developing and validating a nomogram of the risk of failure of internal fixation devices in Chinese patients undergoing spinal internal fixation. We collected data from a total of 1139 patients admitted for spinal internal fixation surgery at the First Affiliated Hospital of Guangxi Medical University from May 2012 to February 2019. Of these, 1050 patients were included in the spinal internal fixation group and 89 patients in the spinal internal fixation device failure group. Patients were divided into training and validation tests. The risk assessment of the failure of the spinal internal fixation device used 14 characteristics. In the training test, the feature selection of the failure model of the spinal internal fixation device was optimized using the least absolute shrinkage and selection operator (LASSO) regression model. Based on the characteristics selected in the LASSO regression model, multivariate logistic regression analysis was used for constructing the model. Identification, calibration, and clinical usefulness of predictive models were assessed using C-index, calibration curve, and decision curve analysis. A validation test was used to validate the constructed model. In the training test, the risk prediction nomogram included gender, age, presence or absence of scoliosis, and unilateral or bilateral fixation. The model demonstrated moderate predictive power with a C-index of 0.722 (95% confidence interval: 0.644-0.800) and the area under the curve (AUC) of 0.722. Decision curve analysis depicted that the failure risk nomogram was clinically useful when the probability threshold for internal fixation device failure was 3%. The C-index of the validation test was 0.761. This novel nomogram of failure risk for spinal instrumentation includes gender, age, presence or absence of scoliosis, and unilateral or bilateral fixation. It can be used for evaluating the risk of instrumentation failure in patients undergoing spinal instrumentation surgery.

3.
Med Sci Monit ; 27: e929149, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33608494

RESUMO

BACKGROUND This retrospective study aimed to identify the factors associated with successful surgical correction of thoracic kyphosis (TK) in 43 patients with adolescent idiopathic scoliosis (AIS) with Lenke type 1 curvature, in which the major curve with the largest Cobb angle was mainly in the thoracic region. MATERIAL AND METHODS We collected data from patients with Lenke 1 AIS. The following parameters were measured: Cobb angle, side-bending Cobb angle, cervical lordosis (CL), TK, lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), the sagittal vertical axis (SVA), the center of a C7 plumb line to the center sacral vertical line (C7-CSVL), correction rate, Ponte osteotomy, flexibility, and screw density. Univariate analysis and multivariate logistic regression analyses were performed. RESULTS Among the 43 cases analyzed, the mean postoperative Cobb angle at the last follow-up, C7-CSVL, SVA, CL, TK, LL, PI, SS, and PT were respectively 21.33±9.47°, 10.41±8.45 mm, 19.68±14.33 mm, 16.19±7.45°, 23.12±7.45°, 50.33±11.37°, 49.70±9.83°, 39.42±8.11°, and 10.16±6.63°. Univariate analysis suggested that preoperative TK, preoperative LL, and Ponte osteotomy were statistically significant (P<0.05), and multivariate analysis suggested that preoperative LL and Ponte osteotomy were statistically significant (P<0.05). CONCLUSIONS The results of this study demonstrated that preoperative TK, preoperative LL, and Ponte osteotomy were related factors for maintaining normal TK. Multivariate analysis suggested that preoperative LL and the use of Ponte osteotomy with full-thickness segmental resection of the spinal posterior column resulted in the successful surgical correction of TK in patients with AIS with Lenke type 1 curvature.

4.
Ying Yong Sheng Tai Xue Bao ; 32(1): 73-81, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33477215

RESUMO

In order to explore how water stress affects the stoichiometric characteristics in leaves, stems, very fine roots (0-1 mm), fine roots (1-2 mm) and thick roots (>2 mm) of three shrub species, we studied the effects of three water treatments [(75±5)%, (55±5)% and (35±5)% of field water capacity (FC)] on the stoichiometric characteristics of different organs of Syringa oblata, Rosa xanthina and Forsythia suspensa in a pot experiment. The results showed that there were significant differences in nitrogen (N) and phosphorus (P) contents, C:N, C:P and N:P of the same organ among the three species. With the intensification of drought stress, there was no significant change of C content in all organs of the three species. The N content increased in leaves, but decreased gradually in stems. The N content in very fine roots and fine roots increased first and then decreased. The P content decreased in leaves and stems, while increased first and then decreased in very fine roots and fine roots. Under drought stress, leaf C:N decreased, C:P and N:P of leaf and stem increased. There was the strongest effect of drought stress on the C:N of very fine roots and C:P and N:P of leaves. There was the least effect of drought stress on C:N, N:P of thick roots and C:P of very fine roots. There was no significant correlation between the contents of C, N in soil and the contents of C, N and P in shrub organs, but soil P content was significantly correlated with the contents of C, N and P in leaves and roots. It was concluded that the relative P limitation in soil was the most important factor affecting the stoichiometric characteristics of shrub organs. Drought had different effects on the stoichiometry of different organs in different shrub species. The stoichio-metry of leaves and very fine roots was more sensitive to drought stress than that of other organs. Drought might affect the stoichiometric characteristics especially related to P in different organs of shrubs, mainly by affecting plant absorption of soil P and its distribution in different organs.


Assuntos
Secas , Nitrogênio , Fósforo , Folhas de Planta , Raízes de Plantas , Solo
5.
Front Genet ; 11: 576566, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193693

RESUMO

Background and Purpose: Head and neck squamous carcinoma (HNSCC), characterized by immunosuppression, is a group of highly heterogeneous cancers. Although immunotherapy exerts a promising influence on HNSCC, the response rate remains low and varies in assorted primary sites. Immunological mechanisms underlying HNSCC pathogenesis and treatment response are not fully understood. This study aimed to develop a differentially expressed genes (DEGs)-based risk model to predict immunotherapy efficacy and stratify prognosis of HNSCC patients. Materials and Methods: The expression profiles of HNSCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. The tumor microenvironment and immune response were estimated by cell type identification via estimating relative subset of known RNA transcripts (CIBERSORT) and immunophenoscore (IPS). The differential expression pattern based on human papillomavirus status was identified. A DEGs-based prognostic risk model was developed and validated. All statistical analyses were performed with R software (version 3.6.3). Results: By using the TCGA database, we identified DKK1, HBEGF, RNASE7, TNFRSF12A, INHBA, and IPIK3R3 as DEGs that were associated with patients' overall survival (OS). Patients were stratified into the high- and low-risk subgroups according to a DEGs-based prognostic risk model. Significant difference in OS was found between the high- and low-risk patients (1.64 vs. 2.18 years, P = 0.0017). In multivariate Cox analysis, the risk model was an independent prognostic factor for OS (hazard radio = 1.06, 95% confidence interval [1.02-1.10], P = 0.004). More CD8+ T cells and regulatory T cells were observed in the low-risk group and associated with a favorable prognosis. The IPS analysis suggested that the low-risk patients possessed a higher IPS score and a higher immunoreactivity phenotype, which were correlated with better immunotherapy response. Conclusion: Collectively, we established a reliable DEGs-based risk model with potential prognostic value and capacity to predict the immunophenotype of HNSCC patients.

6.
Medicine (Baltimore) ; 99(46): e23251, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-33181717

RESUMO

BACKGROUND: In pediatric tumors, immunotherapy exhibits less toxicity than chemotherapy and radiation. The current study aims to identify potential immune targets in immune-related genes of C-C motif chemokine ligand genes (CCLs) and C-C motif chemokine receptors (CCRs) in childhood osteosarcoma (OS) and to explore the underlying molecular mechanisms of childhood OS. METHODS: Firstly, we identified immune-related genes in CCLs and CCRs, these genes were used for functional annotation and interaction analysis. Then, the prognostic value of these genes was evaluated using Kaplan-Meier analysis and multivariate COX regression model. And the potential relationship between risk score and immune infiltrating cells was identified. Finally, gene set enrichment analysis was used to determine the underlying molecular mechanism of OS. Immune-related genes in CCLs and CCRs are inextricably linked. RESULTS: The results of survival analysis of these genes show that CCL5, CCL8, CCR4, and CCR5 are significantly associated with the prognosis of childhood OS. The combined effect survival analysis shows that the co-high expression of these 4 genes has a good prognosis for childhood OS. A prognostic signature model was constructed based on the 4 genes mentioned above, and the result of time-dependent receiver operating characteristic curves showed that this model was a good predictor of childhood OS 3- and 5-year prognosis. In addition, the risk score of the constructed prognostic signature model was closely related to immune infiltration. We also found that CCL5, CCL8, and CCR5 may affect the prognosis of OS through complex regulation among Toll-like receptor signaling pathway, mitogen-activated protein kinase (MAPK) family signaling cascade, and nuclear factor-kappaB pathway, whereas CCR4 affects the prognosis of OS by regulating eukaryotic translation. CONCLUSION: CCL5, CCL8, CCR4, and CCR5 are potential prognostic markers for the prognosis of childhood OS, and the underlying molecular mechanisms of childhood OS have been identified.


Assuntos
Biomarcadores Tumorais/análise , Osteossarcoma/diagnóstico , Prognóstico , Biomarcadores Tumorais/genética , Criança , Detecção Precoce de Câncer/métodos , Detecção Precoce de Câncer/normas , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Imunoterapia/métodos , Estimativa de Kaplan-Meier , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Osteossarcoma/genética , Pediatria/métodos , Pediatria/tendências , Estudos Prospectivos , Análise de Sobrevida
7.
J Neurochem ; 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33165916

RESUMO

Abnormal expression of Ten eleven translocation-2 (Tet2) contributes to the pathogenesis of Alzheimer's disease (AD). However, to date, the role of Tet2 in modulating neuronal morphology upon amyloid-ß (Aß)-induced neurotoxicity has not been shown in a mouse model of AD. Here, we have developed a model of injured mouse hippocampal neurons induced by Aß42 oligomers in vitro. We also investigated the role of Tet2 in injured neurons using recombinant plasmids-induced Tet2 inhibition or over-expression. We found that the reduced expression of Tet2 exacerbated neuronal damage, whereas the increased expression of Tet2 was sufficient to protect neurons against Aß42 toxicity. Our results indicate that the brains of aged APPswe/PSEN1 double-transgenic (2 × Tg-AD) mice exhibit an increase in Aß plaque accumulation and a decrease in Tet2 expression. As a result, we have also explored the underlying mechanisms of Tet2 in cognition and amyloid load in 2 × Tg-AD mice via adeno-associated virus-mediated Tet2 knockdown or over-expression. Recombinant adeno-associated virus was microinjected into bilateral dentate gyrus regions of the hippocampus of the mice. Knocking down Tet2 in young 2 × Tg-AD mice resulted in the same extent of cognitive dysfunction as aged 2 × Tg-AD mice. Importantly, in middle-aged 2 × Tg-AD mice, knocking down Tet2 accelerated the accumulation of Aß plaques, whereas over-expressing Tet2 alleviated amyloid burden and memory loss. Furthermore, our hippocampal RNA-seq data, from young 2 × Tg-AD mice, were enriched with aberrantly expressed lncRNAs and miRNAs that are modulated by Tet2. Tet2-modulated lncRNAs (Malat1, Meg3, Sox2ot, Gm15477, Snhg1) and miRNAs (miR-764, miR-211, and miR-34a) may play a role in neuron formation. Overall, these results indicate that Tet2 may be a potential therapeutic target for repairing neuronal damage and cognitive impairment in AD.

8.
Medicine (Baltimore) ; 99(48): e23409, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33235120

RESUMO

BACKGROUND: Talaromyces marneffei (T marneffei), known as a significant pathogen in patients with AIDS in Southeast Asia, is a dimorphic fungus, which can cause deadly systematic infection in immunocompromised hosts. What is more, the dimorphic phase transition has been reported as a conspicuous process linked with virulence. Interestingly, the yeast form was found in infected individuals, representing the pathogenic phase. However, few researches were found to study the mechanism of dimorphic transition. Thus, a diverse insight into the dimorphic switch mechanism, is urgently needed and we are the first one to research the mechanism of dimorphism. METHODS: Firstly, we investigated the microarray of T. marneffei in the Gene Expression Omnibus database (GEO) for differentially expressed genes (DEGs). Then Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.8 was employed to analyze the underlying enrichment and pathway in biological process of DEGs. Meanwhile, protein-protein interaction (PPI) network was constructed using STRING database. On the strength of the theory that similar amino acid sequences share similar structures, which play a decisive role on the function of protein, three dimensional structures of hub-genes were predicted to further investigate the likely function of hub-genes. RESULTS: GSE51109 was elected as the eligible series for the purpose of our research, including GSM1238923 (GSM23), GSM1238924 (GSM24), and GSM1238925 (GSM25). PMAA_012920, PMAA_028730, PMAA_068140, PMAA_092900, PMAA_032350 were the most remarkable genes in all of the three PPI networks, thus, were viewed as hub-genes. With regard to the three-dimensional construction, except that there was no significant prediction structure of PMAA_092900 with the criterion seq identify > 30%, GMQE: 0-1, QMEAN4: -4-0, the parallel templates for four structures were Crystal structure of Saccharomyces cerevesiae mitochondrial NADP(+)-dependent isocitrate dehydrogenase in complex with isocitrate, Organellar two-pore channels (TPCs), Yeast Isocitrate Dehydrogenase (Apo Form) and Crystal Structure Of ATP-Dependent Phosphoenolpyruvate Carboxykinase From Thermus thermophilus HB8 in order. CONCLUSION: The dimorphic transition of T. marneffei was viewed as a pathogenic factor and DEGs were observed. In-depth study of the function and pathway of DEGs revealed that PMAA_012920, PMAA_028730, PMAA_068140, PMAA_092900, PMAA_032350 were most likely acting as the hub-genes and were likely taking effect through regulating energy metabolism.

9.
Comput Struct Biotechnol J ; 18: 2596-2609, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33033580

RESUMO

Purpose: Visceral fat is an independent risk factor for metabolic and cardiovascular disease. The study aimed to investigate the associations between gut microbiome and visceral fat. Methods: We recruited 32 obese adults and 30 healthy controls at baseline. Among the obese subjects, 14 subjects underwent laparoscopic sleeve gastrectomy (LSG) and were followed 6 months after surgery. Abdominal visceral fat area (VFA) and subcutaneous fat area (SFA) were measured by magnetic resonance imaging. Waist, hipline, waist-to-hip ratio (WHR) and body mass index (BMI) were included as simple obese parameters. Gut microbiome was analyzed by metagenomic sequencing. Results: Among the obese parameters, VFA had the largest number of correlations with the species that were differentially enriched between obese and healthy subjects, following by waist, WHR, BMI, hipline, and SFA. Within the species negatively correlated with VFA, Eubacterium eligens had the strongest correlation, following by Clostridium citroniae, C. symbiosum, Bacteroides uniformis, E. ventriosum, Ruminococcaceae bacterium D16, C. hathewayi, etc. C. hathewayi and C. citroniae were increased after LSG. Functional analyses showed that among all the obese parameters, VFA had strongest correlation coefficients with the obesity-related microbial pathways. Microbial pathways involved in carbohydrate fermentation and biosynthesis of L-glutamate and L-glutamine might contribute to visceral fat accumulation. Conclusions: Visceral fat was more closely correlated with gut microbiome compared with subcutaneous fat, suggesting an intrinsic connection between gut microbiome and metabolic cardiovascular diseases. Specific microbial species and pathways which were closely associated with visceral fat accumulation might contribute to new targeted therapies for metabolic disorders.

10.
Neural Plast ; 2020: 9387560, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123191

RESUMO

Autophagy and apoptosis have a complex interplay in the early embryo development. The development of spiral ganglion neurons (SGNs) in addition to Corti's organ in the mammalian cochlea remains crucial in the first two-week postnatal period. To investigate the roles of apoptosis and autophagy in the development of SGNs, light microscopy was used to observe the morphological changes of SGNs. The number of SGNs was decreased from P1 to P7 and plateaued from P10 to P14. Immunohistochemistry results revealed positive expression of cleaved-caspase3, bcl-2, microtubule-associated protein light chain 3-II (LC3-II), Beclin1, and sequestosome 1 (SQSTM1/P62) in SGNs. The apoptotic bodies and autophagosomes and autolysosomes were also identified by transmission electron microscopy at P1 and P7. Real-time PCR and western blotting results revealed that the apoptotic activity peaked at P7 and the autophagy activity was gradually upregulated along with the development. Taken together, our results for the first time showed that autophagy and apoptosis in SGNs play distinct roles during specific developmental phases in a time-dependent manner.

11.
J Cancer ; 11(23): 6861-6873, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123277

RESUMO

Purpose: The patients diagnosed with colorectal cancer (CRC) are likely to undergo differential outcomes in clinical survival owing to different pathologic stages. However, signatures in association with pathologic evolution and CRC prognosis are not clearly defined. This study aimed to identify pathologic evolution-related genes in CRC based on both single-cell and bulk transcriptomics. Patients and methods: The CRC single-cell transcriptomic dataset (GSE81861, n=590) with clinical information and tumor microenvironmental tissues was collected to identify the pathologic evolution-related genes. The colonic adenocarcinoma and rectum adenocarcinoma transcriptomics from The Cancer Genome Atlas were obtained as the training dataset (n=363) and 5 other CRC transcriptomics cohorts from Gene Expression Omnibus (n=1031) were acquired as validation data. Graph-based clustering analysis algorithm was applied to identify pathologic evolution-related cell populations. Pseudotime analysis was performed to construct the trajectory plot of pathologic evolution and to define hub genes in the evolution process. Cell-type identification by estimating relative subsets of RNA transcripts was then executed to build a novel cell infiltration classifier. The prediction efficacy of this classifier was validated in bulk transcriptomic datasets. Results: Epithelial and T cells were elucidated to be related to the pathologic stages in CRC tissues. Pseudotime analysis and survival analysis indicated that HOXC5, HOXC8 and BMP5 were the marker genes in pathologic evolution process. Our cell infiltration classifier exhibited excellent forecast efficacy in predicting pathologic stages and prognosis of CRC patients. Conclusion: We identified pathologic evolution-related genes in single-cell transcriptomic and proposed a novel specific cell infiltration classifier to forecast the prognosis of CRC patients based on pathologic stage-related hub genes HOXC6, HOXC8 and BMP5.

12.
Microbiome ; 8(1): 133, 2020 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-32919472

RESUMO

BACKGROUND: Antibiotic treatment has a well-established detrimental effect on the gut bacterial composition, but effects on the fungal community are less clear. Bacteria in the lumen of the gastrointestinal tract may limit fungal colonization and invasion. Antibiotic drugs targeting bacteria are therefore seen as an important risk factor for fungal infections and induced allergies. However, antibiotic effects on gut bacterial-fungal interactions, including disruption and resilience of fungal community compositions, were not investigated in humans. We analysed stool samples collected from 14 healthy human participants over 3 months following a 6-day antibiotic administration. We integrated data from shotgun metagenomics, metatranscriptomics, metabolomics, and fungal ITS2 sequencing. RESULTS: While the bacterial community recovered mostly over 3 months post treatment, the fungal community was shifted from mutualism at baseline to competition. Half of the bacterial-fungal interactions present before drug intervention had disappeared 3 months later. During treatment, fungal abundances were associated with the expression of bacterial genes with functions for cell growth and repair. By extending the metagenomic species approach, we revealed bacterial strains inhibiting the opportunistic fungal pathogen Candida albicans. We demonstrated in vitro how C. albicans pathogenicity and host cell damage might be controlled naturally in the human gut by bacterial metabolites such as propionate or 5-dodecenoate. CONCLUSIONS: We demonstrated that antibacterial drugs have long-term influence on the human gut mycobiome. While bacterial communities recovered mostly 30-days post antibacterial treatment, the fungal community was shifted from mutualism towards competition. Video abstract.

13.
Front Oncol ; 10: 874, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612950

RESUMO

Natural killer (NK) cells play a critical role in the antitumor immunity. Ionizing radiation (IR) has a pronounced effect on modifying NK cell biology, while the molecular mechanisms remain elusive. In this review, we briefly introduce the anti-tumor activity of NK cells and summarize the impact of IR on NK cells both directly and indirectly. On one hand, low-dose ionizing radiation (LDIR) activates NK functions while high-dose ionizing radiation (HDIR) is likely to partially impair NK functions, which can be reversed by interleukin (IL)-2 pretreatment. On the other hand, NK functions may be adjusted by other immune cells and the alternated malignant cell immunogenicity under the settings of IR. Various immune cells, such as the tumor-associated macrophage (TAM), dendritic cell (DC), regulatory T cell (Treg), myeloid-derived suppressor cell (MDSC), and tumor exhibited ligands, such as the natural killer group 2 member D ligand (NKG2DL), natural cytotoxicity receptors (NCR) ligand, TNF-related apoptosis-inducing ligand-receptor (TRAIL-R), and FAS, have been involved in this process. Better understanding the molecular basis is a promising way in which to augment NK-cell-based antitumor immunity in combination with IR.

14.
Medicine (Baltimore) ; 99(21): e20268, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32481304

RESUMO

BACKGROUND: Ossification of the posterior longitudinal ligament (OPLL) refers to an ectopic ossification disease originating from the posterior longitudinal ligament of the spine. Pressing on the spinal cord or nerve roots can cause limb sensory and motor disorders, significantly reducing the patient's quality of life. At present, the pathogenesis of OPLL is still unclear. The purpose of this study is to integrate microRNA (miRNA)-mRNA biological information data to further analyze the important molecules in the pathogenesis of OPLL, so as to provide targets for future OPLL molecular therapy. METHODS: miRNA and mRNA expression profiles of GSE69787 were downloaded from Gene Expression Omnibus database and analyzed by edge R package. Funrich software was used to predict the target genes and transcription factors of de-miRNA. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis of differentially expressed genes (DEGs) were carried out based on CLUEGO plug-in in Cytoscape. Using data collected from a search tool for the retrieval of interacting genes online database, a protein-protein interaction (PPI) network was constructed using Cytoscape. The hub gene selection and module analysis of PPI network were carried out by cytoHubba and molecular complex detection, plug-ins of Cytoscape software respectively. RESULTS: A total of 346 genes, including 247 up-regulated genes and 99 down-regulated genes were selected as DEGs. SP1 was identified as an upstream transcription factor of de-miRNAs. Notably, gene ontology enrichment analysis shows that up- and down-regulated DEGs are mainly involved in BP, such as skeletal structure morphogenesis, skeletal system development, and animal organ morphogenesis. Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that only WNT signaling pathway was associated with osteogenic differentiation. Lymphoid enhancer binding factor 1 and wingless-type MMTV integration site family member 2 Wingless-Type MMTV Integration site family member 2 were identified as hub genes, miR-520d-3p, miR-4782-3p, miR-6766-3p, and miR-199b-5p were identified as key miRNAs. In addition, 2 important network modules were obtained from PPI network. CONCLUSIONS: In this study, we established a potential miRNA-mRNA regulatory network associated with OPLL, revealing the key molecular mechanism of OPLL and providing targets for future treatment or prevent its occurrence.


Assuntos
Biologia Computacional/instrumentação , Fator 1 de Ligação ao Facilitador Linfoide/genética , MicroRNAs/genética , Ossificação do Ligamento Longitudinal Posterior/genética , RNA Mensageiro/genética , Proteína Wnt2/genética , Regulação para Baixo/genética , Perfilação da Expressão Gênica/instrumentação , Ontologia Genética , Redes Reguladoras de Genes/genética , Humanos , Ossificação do Ligamento Longitudinal Posterior/patologia , Ossificação do Ligamento Longitudinal Posterior/fisiopatologia , Ossificação do Ligamento Longitudinal Posterior/psicologia , Osteogênese/genética , Mapas de Interação de Proteínas/genética , Qualidade de Vida , Coluna Vertebral/patologia , Fatores de Transcrição/genética , Regulação para Cima/genética , Via de Sinalização Wnt/genética
15.
Medicine (Baltimore) ; 99(18): e19986, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358373

RESUMO

BACKGROUND: The incidence of triple negative breast cancer (TNBC) is at a relatively high level, and our study aimed to identify differentially expressed genes (DEGs) in TNBC and explore the key pathways and genes of TNBC. METHODS: The gene expression profiling (GSE86945, GSE86946 and GSE102088) data were obtained from Gene Expression Omnibus Datasets, DEGs were identified by using R software, Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of DEGs were performed by the Database for Annotation, Visualization and Integrated Discovery (DAVID) tools, and the protein-protein interaction (PPI) network of the DEGs was constructed by the STRING database and visualized by Cytoscape software. Finally, the survival value of hub DEGs in breast cancer patients were performed by the Kaplan-Meier plotter online tool. RESULTS: A total of 2998 DEGs were identified between TNBC and health breast tissue, including 411 up-regulated DEGs and 2587 down-regulated DEGs. GO analysis results showed that down-regulated DEGs were enriched in gene expression (BP), extracellular exosome (CC), and nucleic acid binding, and up-regulated were enriched in chromatin assembly (BP), nucleosome (CC), and DNA binding (MF). KEGG pathway results showed that DEGs were mainly enriched in Pathways in cancer and Systemic lupus erythematosus and so on. Top 10 hub genes were picked out from PPI network by connective degree, and 7 of top 10 hub genes were significantly related with adverse overall survival in breast cancer patients (P < .05). Further analysis found that only EGFR had a significant association with the prognosis of triple-negative breast cancer (P < .05). CONCLUSIONS: Our study showed that DEGs were enriched in pathways in cancer, top 10 DEGs belong to up-regulated DEGs, and 7 gene connected with poor prognosis in breast cancer, including HSP90AA1, SRC, HSPA8, ESR1, ACTB, PPP2CA, and RPL4. These can provide some guidance for our research on the diagnosis and prognosis of TNBC, and further research is needed to evaluate their value in the targeted therapy of TNBC.


Assuntos
Mineração de Dados/métodos , Regulação Neoplásica da Expressão Gênica/fisiologia , Neoplasias de Mama Triplo Negativas/genética , Bases de Dados Genéticas , Regulação para Baixo , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Análise de Sobrevida , Neoplasias de Mama Triplo Negativas/mortalidade , Regulação para Cima
16.
Biomolecules ; 10(4)2020 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-32316682

RESUMO

Protein structures play a very important role in biomedical research, especially in drug discovery and design, which require accurate protein structures in advance. However, experimental determinations of protein structure are prohibitively costly and time-consuming, and computational predictions of protein structures have not been perfected. Methods that assess the quality of protein models can help in selecting the most accurate candidates for further work. Driven by this demand, many structural bioinformatics laboratories have developed methods for estimating model accuracy (EMA). In recent years, EMA by machine learning (ML) have consistently ranked among the top-performing methods in the community-wide CASP challenge. Accordingly, we systematically review all the major ML-based EMA methods developed within the past ten years. The methods are grouped by their employed ML approach-support vector machine, artificial neural networks, ensemble learning, or Bayesian learning-and their significances are discussed from a methodology viewpoint. To orient the reader, we also briefly describe the background of EMA, including the CASP challenge and its evaluation metrics, and introduce the major ML/DL techniques. Overall, this review provides an introductory guide to modern research on protein quality assessment and directions for future research in this area.

17.
Int J Ment Health Nurs ; 29(5): 772-785, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32223070

RESUMO

Postpartum depression is a serious mental illnessdisorder that occurs after delivery and is one of the most common post-partum complications. With the increasing popularity and extensive use of smartphones worldwide and the fact that China has become the country with the largest number of smartphone users, it is necessary to have a deep understanding of the use and influence of smartphones and discuss the role of smartphone applications in postpartum depression. This study evaluated and analysed the contents of all postpartum depression applications available in China, applying the US Preventive Services Task Force Recommendation Statement (Interventions to Prevent Perinatal Depression) and expert consensus on the guidelines for the prevention and treatment of postpartum depression. We used the keywords 'postpartum depression; and 'PPD' to search Android, iOS, and WeChat in the Chinese application market. Two reviewers agreed on the coding guidelines and coded the content and functionality of the application through content analysis to determine its intervention and adherence to the guidelines. In addition, we used the Mobile App Rating Scale (MARS) to evaluate the application for engagement, functionality, aesthetics, and information domains and recorded the features of the postpartum depression application. The current findings suggest that despite the recent expansion of smartphone platforms and increased availability of applications, existing Chinese apps for postpartum depression have low levels of adherence to clinical practice-based guidelines. New apps need to be developed, and existing apps need to be revised following evidence-based principles.

18.
Med Sci Monit ; 26: e919888, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32210223

RESUMO

BACKGROUND This retrospective study aimed to investigate the risk factors associated with the recurrence of L5-S1 disc herniation after percutaneous endoscopic transforaminal discectomy (PETD). MATERIAL AND METHODS There were 484 patients L5-S1 disc herniation who underwent PETD who were divided into the recurrence group (n=46) and the non-recurrence group (n=438). Transforaminal endoscopic approaches included modifications of the Yeung endoscopy spine system (YESS) (the intraforaminal intradiscal approach) and the transforaminal endoscopic spine system (TESSYS) (intraforaminal extradiscal approach). Demographic and clinical characteristics and imaging data were analyzed. The two study groups were compared to determine the factors associated with the recurrence of L5-S1 disc herniation. The patients underwent postoperative follow-up for between one and four years. RESULTS At follow-up, 9.504% of patients (46/484) with the recurrence of L5-S1 disc herniation following PETD when compared with the non-recurrence group showed no significant difference for time to return to work, gender, history of diabetes mellitus, trauma, duration of symptoms, smoking and alcohol history, hypertension, location of disc herniation, transverse process length, intervertebral space height, and pelvic incidence angle (P>0.05). However, age, body mass index (BMI), the degree of disc degeneration, sagittal range of motion, lumbar lordosis angle, and sacral slope were significantly associated with the recurrence of L5-S1 disc herniation following PETD (P<0.05). Logistic regression analysis supported these main associations. CONCLUSIONS The recurrence of L5-S1 disc herniation following PETD was significantly associated with increased age and BMI, more severe disc degeneration, increased sagittal range of motion, increased lumbar lordosis, and sacral slope.

19.
Medicine (Baltimore) ; 99(3): e18790, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32011476

RESUMO

BACKGROUND: Chordoma is a rare malignant tumor with limited treatment. Recent studies have shown that the proliferation and invasion ability of chordoma after Tumor necrosis factor alpha (TNF-α) treatment is enhanced, which may activate the gene pathway involved in the development of chordoma. This study tends to identify differentially expressed genes (DEGs) before and after treatment of TNF-α in chordoma cell line, providing a new target for future molecular therapy of chordoma. METHODS: The gene expression profile of GSE101867 was downloaded from the Gene Expression Omnibus database, and the differentially expressed genes were obtained using GEO2R. Based on the CLUEGO plugin in Cytoscape, DEGs functionality and enrichment analysis. A protein-protein interaction (PPI) network was constructed using Cytoscape based on data collected from the STRING online dataset. The Hub genes are selected from the CytoHubba, the first 20 genes that coexist with the KEGG tumor-related pathway. RESULTS: A total of 560 genes, including 304 up-regulated genes and 256 down-regulated genes, were selected as DEGs. Obviously, GO analysis shows that up-regulated and down-regulated DEGs are mainly enriched in biological processes such as synaptic tissue, cell adhesion, extracellular matrix organization and skeletal system development. DEGs are mainly enriched in tumor-associated pathways such as Pi3k-akt Signal path, Rap1 signal path. Three key genes were identified: PDGFRB, KDR, FGF2. All of these genes are involved in the tumor-associated pathways described previously. CONCLUSION: This study is helpful in understanding the molecular characteristics of chordoma development. Hub genes PDGFRB, KDR, FGF2 and pi3k-akt signaling pathway, Rap1 signaling pathway will become a new target for the future treatment of chordoma.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/metabolismo , Cordoma/tratamento farmacológico , Cordoma/metabolismo , Fator de Necrose Tumoral alfa/uso terapêutico , Neoplasias Ósseas/genética , Linhagem Celular Tumoral , Cordoma/genética , Biologia Computacional , Perfilação da Expressão Gênica , Humanos , Análise em Microsséries
20.
J Orthop Translat ; 20: 73-79, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31908936

RESUMO

Background and objective: Existing orthopaedic robotic systems are almost restricted to provide guidance for trajectory direction. In the present study, a novel spinal robotic system with automatic drilling power was introduced. The aim of this study is to evaluate the feasibility and safety in pedicle screw â€‹insertion of posterior lumbar interbody fusion assisted by this novel robotic system. Methods and materials: A randomised controlled trial was conducted for 17 participants who were required posterior lumbar interbody fusion process. Seven (3 M/4 F) were randomly assigned to the robot-assisted group (RA group), and the other ten (4 M/6 F) were assigned to the conventional technique group (FH group). A novel robotic system was used in the RA group. All measurements were based on postoperative computed tomography (CT) data. Accuracy of screw insertion was determined using the Gertzbein and Robbins Scale. Precision was measured by the entry point deviation distance and the trajectory rotation. Other variables included operation time, radiation time, length of stay, and screw-related complications. Result: A total of 82 pedicle screws were placed in the 17 participants. In the RA group, 90.6% of screws placed were Grade A, and 9.4% were Grade B. In the FH group, 78.0% of screws were Grade A, 20.0% were Grade B, and 2.0% were Grade C. No statistical difference was found in the operation time, radiation time per case, and length of stay between both groups. The radiation time per screw is significantly lower in the RA group. No screw-related complications or revision occurred in the present study. Conclusion: The outcome of screw accuracy of this robotic system was comparable with that of experienced surgeons, and no screw-related complication was found in the RA group during hospitalisation. In addition, radiation time per screw in the robotic group was significantly lower than that in the conventional group, which shows the potential to reduce radiation exposure of pedicle screw fixation assisted by this robotic system. Translational potential: Our study shows that pedicle screw fixation assisted by "Orthbot" system is accurate and safe. It is concluded that this novel robotic system offers a new option for internal implantation in spine surgery.

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