Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 114
Filtrar
1.
Fa Yi Xue Za Zhi ; 38(1): 53-58, 2022 Feb 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-35725704

RESUMO

OBJECTIVES: To explore the application value of virtual autopsy to obtain key evidence information on drowned corpses and its application value of virtual autopsy in the diagnosis of drowning. METHODS: In this study, 7 corpses were selected as the research objects. The image data of corpses were collected by computed tomography (CT) before conventional autopsy. The characteristics of corpses were observed through image reading, combined with virtual measurement indexes, and compared with 15 non-drowned corpses. RESULTS: The postmortem CT of drowning showed the more fluid in respiratory tract than the non-drowning, and ground-glass opacities in the lung. The statistical volume of fluid in the sinus (maxillary sinus and sphenoid sinus) was (10.24±4.70) mL in drowning cases and (2.02±2.45) mL in non-drowning cases. The average CT value of fluid in the sinus, left atrial blood and gastric contents in drowning cases were (15.91±17.20), (52.57±9.24) and (10.33±12.81) HU, respectively, which were lower than those in non-drowning cases (P<0.05). CONCLUSIONS: The comprehensive consideration of multiple characteristic image manifestations and the virtual measurement indexes are helpful to the forensic pathological diagnosis of drowning. Virtual autopsy can be used as an auxiliary method in the forensic diagnosis of drowning.


Assuntos
Afogamento , Autopsia/métodos , Cadáver , Afogamento/diagnóstico por imagem , Patologia Legal/métodos , Humanos , Tomografia Computadorizada por Raios X/métodos
2.
Front Mol Biosci ; 9: 876603, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35573726

RESUMO

Background: Glioblastoma (GBM) is the most invasive brain tumors, and it is associated with high rates of recurrence and mortality. The purpose of this study was to investigate the expression of RBM8A in GBM and the potential influence of its expression on the disease. Methods: Levels of RBM8A mRNA in GBM patients and controls were examined in The Cancer Genome Atlas (TCGA), GSE16011 and GSE90604 databases. GBM samples in TCGA were divided into RBM8Ahigh and RBM8Alow groups. Differentially expressed genes (DEGs) between GBM patients and controls were identified, as were DEGs between RBM8Ahigh and RBM8Alow groups. DEGs common to both of these comparisons were analyzed for coexpression and regression analyses. In addition, we identified potential effects of RBM8A on competing endogenous RNAs, immune cell infiltration, methylation modifications, and somatic mutations. Results: RBM8A is expressed at significantly higher levels in GBM than control samples, and its level correlates with tumor purity. We identified a total of 488 mRNAs that differed between GBM and controls as well as between RBM8Ahigh and RBM8Alow groups, which enrichment analysis revealed to be associated mainly with neuroblast proliferation, and T cell immune responses. We identified 174 mRNAs that gave areas under the receiver operating characteristic curve >0.7 among coexpression module genes, of which 13 were significantly associated with overall survival of GBM patients. We integrated 11 candidate mRNAs through LASSO algorithm, then nomogram, risk score, and decision curve analyses were analyzed. We found that RBM8A may compete with DLEU1 for binding to miR-128-1-5p, and aberrant RBM8A expression was associations with tumor infiltration by immune cells. Some mRNAs associated with GBM prognosis also appear to be methylated or mutated. Conclusions: Our study strongly links RBM8A expression to GBM pathobiology and patient prognosis. The candidate mRNAs identified here may lead to therapeutic targets against the disease.

3.
Front Aging Neurosci ; 14: 770136, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35592696

RESUMO

The incidence of Alzheimer's disease (AD) is constantly increasing as the older population grows, and no effective treatment is currently available. In this study, we focused on the identification of AD molecular subtypes to facilitate the development of effective drugs. AD sequencing data collected from the Gene Expression Omnibus (GEO) database were subjected to cluster sample analysis. Each sample module was then identified as a specific AD molecular subtype, and the biological processes and pathways were verified. The main long non-coding RNAs and transcription factors regulating each "typing pathway" and their potential mechanisms were determined using the RNAInter and TRRUST databases. Based on the marker genes of each "typing module," a classifier was developed for molecular typing of AD. According to the pathways involved, five sample clustering modules were identified (mitogen-activated protein kinase, synaptic, autophagy, forkhead box class O, and cell senescence), which may be regulated through multiple pathways. The classifier showed good classification performance, which may be useful for developing novel AD drugs and predicting their indications.

4.
Medicine (Baltimore) ; 101(2): e28544, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35029212

RESUMO

RATIONALE: Postmortem imaging (PMI), including computed tomography (PMCT), postmortem computed tomography angiography (PMCTA), and postmortem magnetic resonance imaging (PMMRI), is rapidly becoming effective and a practical method in forensic medicine. This study aimed to present a specific forensic case in which the PMI approach and its applications were used. PATIENT CONCERNS: A 40-year-old male patient had moderate unilateral nose bleeding constantly 10 times after suffering from a head injury induced by a car accident. After a bilateral massive nose bleeding for the last time, he died from hemorrhagic shock. Traumatic internal carotid artery pseudoaneurysm (TICAP) was suspected in this patient. DIAGNOSIS, INTERVENTIONS, AND OUTCOMES: A whole-body scanning was performed using PMCT and PMMRI. Then, PMCTA using left ventricular cardiac puncture was also implemented. A water-soluble contrast agent was injected into the left ventricle and pumped toward the intracranial, followed by a repeated whole-body PMCT scan. The PMCT/PMMRI detected a high-density/signal mass inside the left sphenoid sinus. The PMCTA detected a distinct leakage of the contrast agent into the left sphenoid sinus from an adjacent aneurysm of the C3 section of the left internal carotid artery. Autopsy and histology confirmed a TICAP inside the sphenoid sinus. LESSONS: This case showed that the PMI was of great value for identifying the cause of death in special cases. When vascular lesions are suspected in the body, PMI and especially the PMCTA approach may be an effective detection method.


Assuntos
Falso Aneurisma/diagnóstico por imagem , Autopsia/métodos , Artéria Carótida Interna/diagnóstico por imagem , Meios de Contraste , Adulto , Falso Aneurisma/etiologia , Angiografia por Tomografia Computadorizada , Evolução Fatal , Hemorragia , Humanos , Masculino
5.
J Pharm Biomed Anal ; 210: 114546, 2022 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-34972069

RESUMO

A sensitive, accurate, simple, and rapid analytical UHPLC-MS/MS method was developed for identification and quantification of koumine, gelsemine, and gelsenicine in human hair. Approximately 10 mg of hair was extracted with methanol by cryogenic grinding. The limits of detection (LODs) ranged from 1 to 5 pg/mg, and the limits of quantitation (LOQs) ranged from 2 to 10 pg/mg. The method was linear over a concentration range from the LOQs to 1000 pg/mg, and the linear correlation (R2) of the calibration curves was above 0.998 for all three analytes. The bias varied from -6.5-13.1%, while the intra- and inter-day precision relative standard deviation (RSD) values were 4.3-12.4% and 3.7-13.2%, respectively. Recoveries ranged from 79.3% to 103.5%, and matrix effects ranged from 74.3% to 105.5%. The described method was used for the quantitative determination of koumine, gelsemine, and gelsenicine in a human hair sample from a Gelsemium elegans poisoning case. The highest concentrations of koumine, gelsemine, and gelsenicine were 27.2, 18.1, and 4.2 pg/mg, respectively, and corresponded to the segment associated with the ingestion period. To our knowledge, this is the first study to describe hair analysis in a G. elegans poisoning case and to provide quantitative toxicological findings.


Assuntos
Gelsemium , Alcaloides , Cromatografia Líquida de Alta Pressão , Humanos , Alcaloides Indólicos , Espectrometria de Massas em Tandem
7.
Front Oncol ; 11: 736941, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804926

RESUMO

BACKGROUND: Glioblastoma (GBM) is a prevalent brain malignancy with an extremely poor prognosis, which is attributable to its invasive biological behavior. The RNA-binding motif protein 8A (RBM8A) has different effects on various human cancers. However, the role of RBM8A in GBM progression remains unclear. METHODS: We investigated the expression levels of RBM8A in 94 GBM patients and explored the correlation between RBM8A expression and patient prognosis. Using in vitro and in vivo assays, combined with GBM sequencing data from the Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA), we examined whether and how RBM8A contributes to GBM progression. RESULTS: RBM8A was up-regulated in GBM tissues, and its higher expression correlated with worse prognosis. Knockdown of RBM8A inhibited GBM progression and invasion ability both in vitro and in vivo. On the contrary, overexpression of RBM8A promoted GBM progression and invasion ability. Enrichment analysis of differentially expressed genes in GBM data identified the Notch1/STAT3 network as a potential downstream target of RBM8A, and this was supported by molecular docking studies. Furthermore, we demonstrated that RBM8A regulates the transcriptional activity of CBF1. The γ-secretase inhibitor DAPT significantly reversed RBM8A-enhanced GBM cell proliferation and invasion, and was associated with down-regulation of p-STAT3 and Notch1 protein. Finally, the gene set variance analysis score of genes involved in regulation of the Notch1/STAT3 network by RBM8A showed good diagnostic and prognostic value for GBM. CONCLUSIONS: RBM8A may promote GBM cell proliferation and migration by activating the Notch/STAT3 pathway in GBM cells, suggesting that RBM8A may serve as a potential therapeutic target for the treatment of GBM.

8.
Acta Bioeng Biomech ; 23(2): 33-40, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34846044

RESUMO

PURPOSE: The purpose of the current study was to develop and validate a finite element (FE) pedestrian model with high computational efficiency and stability using a novel modeling approach. METHODS: Firstly, a novel modeling approach of using hollow structures (HS) to simulate the mechanical properties of soft tissues under impact loading was proposed and evaluated. Then, an FE pedestrian model was developed, employing this modeling approach based on the Total Human Model for Safety (THUMS) pedestrian model, named as THUMS-HS model. Finally, the biofidelity of the THUMS-HS model was validated against cadaver test data at both segment and full-body level. RESULTS: The results show that the proposed hollow structures can simulate the mechanical properties of soft tissues and the predictions of the THUMS-HS model show good agreement with the cadaver test data under impact loading. Simulations also prove that the THUMS-HS model has high computational efficiency and stability. CONCLUSIONS: The proposed modeling approach of using hollow structures to simulate the mechanical properties of soft tissues is plausible and the THUMS-HS model could be used as a valid, efficient and robust numerical tool for analysis of pedestrian safety in vehicle collisions.


Assuntos
Pedestres , Acidentes de Trânsito/prevenção & controle , Fenômenos Biomecânicos , Análise de Elementos Finitos , Corpo Humano , Humanos , Modelos Biológicos
9.
Front Aging Neurosci ; 13: 731180, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616287

RESUMO

Alzheimer's disease (AD) is a common neurodegenerative disease. Its onset is insidious and its progression is slow, making diagnosis difficult. In addition, its underlying molecular and cellular mechanisms remain unclear. In this study, clustering analysis was performed on single-cell RNA sequencing (scRNA-seq) data from the prefrontal cortex of 48 AD patients. Each sample module was identified to be a specific AD cell type, eight main brain cell types were identified, and the dysfunctional evolution of each cell type was further explored by pseudo-time analysis. Correlation analysis was then used to explore the relationship between AD cell types and pathological characteristics. In particular, intercellular communication between neurons and glial cells in AD patients was investigated by cell communication analysis. In patients, neuronal cells and glial cells significantly correlated with pathological features, and glial cells appear to play a key role in the development of AD through ligand-receptor axis communication. Marker genes involved in communication between these two cell types were identified using five types of modeling: logistic regression, multivariate logistic regression, least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM). LASSO modeling identified CXCR4, EGFR, MAP4K4, and IGF1R as key genes in this communication. Our results support the idea that microglia play a role in the occurrence and development of AD through ligand-receptor axis communication. In particular, our analyses identify CXCR4, EGFR, MAP4K4, and IGF1R as potential biomarkers and therapeutic targets in AD.

10.
Cancer Cell Int ; 21(1): 509, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556138

RESUMO

BACKGROUND: Our previous bioinformatics-based study found that midkine (MDK) was associated with poor prognosis of glioblastoma (GBM). However, the mechanism of MDK in GBM remains elusive. METHODS: A public GBM-related dataset and GBM tissues from our center were used validate the aberrant expression of MDK in GBM at the RNA and protein levels. The relationship between MDK expression and survival of GBM patients was also explored through survival analysis. Subsequently, we identified MDK-related GBM-specific genes using differential expression analysis. Functional enrichment analyses were performed to reveal their potential biological functions. CCK-8, 5-ethynyl-2'-deoxyuridine, and Matrigel-transwell assays were performed in GBM cell lines in which MDK was knocked out or overexpressed in order assess the effects of MDK on proliferation, migration, and invasion of GBM cells. Western blotting was performed to detect candidate proteins. RESULTS: Our study showed MDK is a promising diagnostic and prognostic biomarker for GBM because it is highly expressed in the disease and it is associated with poor prognosis. MDK is involved in various cancer-related pathways, such as PI3K-Akt signaling, the cell cycle, and VEGF signaling. A comprehensive transcriptional regulatory network was constructed to show the potential pathways through which MDK may be involved in GBM. In vitro, Overexpression of MDK augmented proliferation, migration, and invasion of GBM cell lines, whereas suppression of MDK led to the opposite effects. Furthermore, our study confirmed that MDK promotes the progression of GBM by activating the PI3K-Akt signaling pathway. CONCLUSIONS: Our present study proposes that MDK promotes GBM by activating the PI3K-Akt signaling pathway, and it describes a potential regulatory network involved.

11.
Int J Gen Med ; 14: 4731-4744, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456585

RESUMO

OBJECTIVE: Ischemic stroke (IS) is a major cause of severe disability. This study aimed to identify potential biomarkers closely related to IS diagnosis and treatment. METHODS: Profiles of gene expression were obtained from datasets GSE16561, GSE22255, GSE112801 and GSE110993. Differentially expressed mRNAs between IS and controls were then subjected to weighted gene co-expression network analysis as well as multiscale embedded gene co-expression network analysis. The intersection of the two sets of module genes was subjected to analyses of functional enrichment and of microRNAs (miRNAs) regulation. Then, the area under receiver operating characteristic curves (AUC) was calculated to assess the ability of genes to discriminate IS patients from controls. IS diagnostic signatures were constructed using least absolute shrinkage and selection operator regression. RESULTS: A total of 234 common co-expression network genes were found to be potentially associated with IS. Enrichment analysis found that these genes were mainly associated with inflammation and immune response. The aberrantly expressed miRNAs (hsa-miR-651-5p, hsa-miR-138-5p, hsa-miR-9-3p and hsa-miR-374a-3p) in IS had regulatory effects on IS-related genes and were involved in brain-related diseases. We used the criterion AUC > 0.7 to screen out 23 hub genes from IS-related genes in the GSE16561 and GSE22255 datasets. We obtained an 8-gene signature (ADCY4, DUSP1, ATP5F1, DCTN5, EIF3G, ELAVL1, EXOSC7 and PPIE) from the training set of GSE16561 dataset, which we confirmed in the validation set of GSE16561 dataset and in the GSE22255 dataset. The genes in this signature were highly accurate for diagnosing IS. In addition, the 8-gene signature significantly correlated with infiltration by immune cells. CONCLUSION: These findings provide new clues to molecular mechanisms and treatment targets in IS. The genes in the signature may be candidate markers and potential gene targets for treatments.

12.
Am J Forensic Med Pathol ; 42(3): 258-262, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34397510

RESUMO

ABSTRACT: Postmortem computed tomography (PMCT), PMCT angiography, and 3-dimensonal (3D) printing technology are increasingly applied to forensic practice. Although their effectiveness is undeniably confirmed, their potential role in practice still needs to be further explored. Here, we report a typical case in which such 4 technologies were applied to a woman found dead with stomach content beneath the head on the pillow in her residence. At first, the cause of death was simply considered as hypertensive cerebral hemorrhage after preliminary examination. However, the initial judgment was questioned by her family for her devoid of hypertension history. As indicated by the targeted PMCT with cerebral angiography, the woman died of pathological cerebral hemorrhage due to arteriovenous malformation, which was still unconvincing enough for the family because in violent death, some cerebral hemorrhage could also be located in the same position. Finally, the family came to be convinced when the close connection between the deformed blood vessels and hematoma was perfectly demonstrated by the application of 3D printing technology. This study proved that it can be an efficient tool for identifying the cause of death when the integration is made of 3D printing technology and PMCT angiography, as a more intuitive evidence of forensic science.


Assuntos
Malformações Arteriovenosas/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Angiografia por Tomografia Computadorizada , Morte Súbita/etiologia , Impressão Tridimensional , Adulto , Angiografia Cerebral , Feminino , Humanos , Ruptura Espontânea/diagnóstico
13.
Forensic Sci Res ; 6(2): 152-158, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34377573

RESUMO

It may be difficult to distinguish the cause of death in drowning cases without specific findings. The aim of this study was to explore the forensic value of thoracic postmortem computed tomography (PMCT) using routine images and three-dimensional (3D) image reconstructions. The imaging data of PMCT examinations of six drowning cadavers, aged 21-54 years, were analyzed. Twelve victims of sudden death from coronary artery disease (CAD) were chosen as a control group. After 3D bilateral lung images were reconstructed using image processing software, an interactive medical image control system was used to measure and analyze parameters including lung volume, lung volume ratio, mean CT value of the whole lung, and lung CT value distribution curves. Lung volume and lung volume ratio were used to assess the shape changes of the lung. Lung CT value distribution curves showed the corresponding number of pixels of the different CT values in the lung image. Lung volume was not significantly larger in drowning cases (mean 2 958 cm3) than in controls (mean 2 342 cm3). Lung volume ratio values in the drowning group (mean 0.3156) were greater than those in the control group (mean 0.2763); (P = 0.02). There was no significant difference between the drowning and control group in the mean CT value of the whole lung. There were differences between lung CT value distribution curves in drowning victims and controls, with drowning victims showing a single peak and CAD cases showing a bimodal distribution. Thoracic PMCT is helpful for the forensic medical diagnosis of drowning. Lung volume ratio and lung CT value distribution are potential indicators to distinguish between drowning and CAD.

14.
Int J Gen Med ; 14: 3213-3223, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34262334

RESUMO

PURPOSE: Type 2 diabetes mellitus (T2DM) increases the risk of ischemic stroke and poor prognosis. This study aimed to identify molecular mechanisms that are dysregulated in T2DM-associated ischemic stroke and candidate genes that might serve as biomarkers. METHODS: The top 25% variance genes in the GSE21321 and GSE22255 datasets were analyzed for coexpression. The differentially expressed mRNAs (DEmRs) between patients with T2DM or ischemic stroke and controls were analyzed. Then, the union of overlapping coexpressed genes and overlapping DEmRs was analyzed. The miRNAs differentially expressed in T2DM-associated ischemic stroke were also analyzed. CIBERSORT was used to evaluate the levels of infiltration by immune cells in T2DM-associated stroke. RESULTS: Thirteen coexpression modules were identified in T2DM and 10 in ischemic stroke, and 594 module genes were shared between the two conditions. A total of 4452 mRNAs differentially expressed between T2DM patients and controls were identified, as were 2390 mRNAs differentially expressed between ischemic stroke and controls. The 771 union genes were enriched mainly in immune-related biological functions and signaling pathways. UBE2N, TGFB3, EXOSC1, and VIM were identified as candidate markers. In addition, we identified miR-576-3p as having the most regulatory roles in both T2DM and ischemic stroke. Mast cell activation was significantly down-regulated in T2DM but up-regulated in ischemic stroke. CONCLUSION: These findings provide numerous testable hypotheses about the pathways underlying T2DM-associated ischemic stroke, which may help identify therapeutic targets.

15.
Clin Interv Aging ; 16: 1071-1084, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34140767

RESUMO

PURPOSE: Carotid atherosclerosis is a kind of systemic atherosclerosis in the carotid arteries. However, the efficiency of treatment is insufficient. Therefore, it is urgent to find therapeutic targets and deepen the understanding of carotid atherosclerosis. MATERIALS AND METHODS: In this study, we analyzed differentially expressed genes (DEGs) between atheroma plaque and macroscopically intact tissue (control samples). Furthermore, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) enrichment analysis based on the DEGs. Four methods were used to identify the hub genes in the protein-protein interaction networks of the DEGs. Furthermore, we also performed network module analysis to reveal carotid atherosclerosis-related gene modules and biological functions. RESULTS: The enrichment results showed that the biological functions were related to inflammation, immunity, chemokine and cell adhesion molecule, such as PIK-Akt signaling pathway, Rap1 signaling pathway, MAPK signaling pathway, NOD-like receptor signaling pathway and B cell receptor signaling pathway. In addition, we screened the hub genes. A total of 16 up-regulated genes (C3AR1, CCR1, CCR2, CD33, CD53, CXCL10, CXCL8, CXCR4, CYBB, FCER1G, FPR2, ITGAL, ITGAM, ITGAX, ITGB2, and LILRB2) were identified as hub genes. A total of 5 gene modules were obtained. We found that biological functions obtained for each cluster were mostly related to immunity, chemokines and cell adhesion molecules. CONCLUSION: The present study identified key DEGs in atheroma plaque compared with control samples. The key genes involved in the development of carotid atherosclerosis may provide valuable therapeutic targets for carotid atherosclerosis.


Assuntos
Doenças das Artérias Carótidas/genética , Perfilação da Expressão Gênica/métodos , Mapas de Interação de Proteínas/genética , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/metabolismo , Biologia Computacional/métodos , Regulação para Baixo/genética , Ontologia Genética/estatística & dados numéricos , Redes Reguladoras de Genes , Humanos , Placa Aterosclerótica , Transdução de Sinais , Regulação para Cima
16.
Int J Gen Med ; 14: 1739-1750, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33986612

RESUMO

PURPOSE: This study aimed to identify genes that may be effective in diagnosing or treating diabetic retinopathy (DR), the most common complication of diabetes mellitus (DM). METHODS: Differentially expressed genes (DEGs) were identified between DR and DM in GSE146615 dataset. DEGs that were consistently up- or down-regulated under both standard glucose and high glucose conditions were identified as common genes and used to generate a protein-protein interaction network and modules. The module genes were assessed for the area under the receiver operating characteristic curve (AUC), leading to the identification of hub genes. Differentially methylated probes in GSE76169 were also compared with common DEGs to identify specific methylation markers of DR. Enrichment analysis was used to explore the biological characteristics. The Short Time-series Expression Miner algorithm was used to identify genes that were progressively dysregulated in the sequence: healthy controls < DM < DR. RESULTS: A total of 1917 common genes were identified for seven modules. The eight genes with AUC > 0.8 under high glucose and standard glucose conditions were considered as hub genes. The module genes were significantly enriched during vascular smooth muscle cell development and regulation of oxygen metabolism, while 92 methylation markers were involved in the similar terms. Among the progressively dysregulated genes, three intersection genes under both standard glucose and high glucose conditions were found to be module genes and were considered as key genes. CONCLUSION: We identified eight potential DR-specific diagnostic and therapeutic genes, whose abnormal expression can cause oxidative stress, thus favoring the course of the disease.

17.
Infect Dis Poverty ; 10(1): 71, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34001244

RESUMO

BACKGROUND: Coronavirus disease 2019 (COVID-19) has killed over 2.5 million people worldwide, but effective care and therapy have yet to be discovered. We conducted this analysis to better understand tocilizumab treatment for COVID-19 patients. MAIN TEXT: We searched major databases for manuscripts reporting the effects of tocilizumab on COVID-19 patients. A total of 25 publications were analyzed with Revman 5.3 and R for the meta-analysis. Significant better clinical outcomes were found in the tocilizumab treatment group when compared to the standard care group [odds ratio (OR) = 0.70, 95% confidential interval (C): 0.54-0.90, P = 0.007]. Tocilizumab treatment showed a stronger correlation with good prognosis among COVID-19 patients that needed mechanical ventilation (OR = 0.59, 95% CI, 0.37-0.93, P = 0.02). Among stratified analyses, reduction of overall mortality correlates with tocilizumab treatment in patients less than 65 years old (OR = 0.68, 95% CI: 0.60-0.77, P < 0.00001), and with intensive care unit patients (OR = 0.62, 95% CI: 0.55-0.70, P < 0.00001). Pooled estimates of hazard ratio showed that tocilizumab treatment predicts better overall survival in COVID-19 patients (HR = 0.45, 95% CI: 0.24-0.84, P = 0.01), especially in severe cases (HR = 0.58, 95% CI 0.49-0.68, P < 0.00001). CONCLUSIONS: Our study shows that tocilizumab treatment is associated with a lower risk of mortality and mechanical ventilation requirement among COVID-19 patients. Tocilizumab may have substantial effectiveness in reducing mortality among COVID-19 patients, especially among critical cases. This systematic review provides an up-to-date evidence of potential therapeutic role of tocilizumab in COVID-19 management.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , COVID-19/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/mortalidade , COVID-19/terapia , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Respiração Artificial , Resultado do Tratamento
18.
Front Cardiovasc Med ; 8: 631650, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34055926

RESUMO

Background: To explore the association of DNA methylation and gene expression in the pathology of obesity. Methods: (1) Genomic DNA methylation and mRNA expression profile of visceral adipose tissue (VAT) were performed in a comprehensive database of gene expression in obese and normal subjects. (2) Functional enrichment analysis and construction of differential methylation gene regulatory networks were performed. (3) Validation of the two different methylation sites and corresponding gene expression was done in a separate microarray dataset. (4) Correlation analysis was performed on DNA methylation and mRNA expression data. Results: A total of 77 differentially expressed mRNAs matched with differentially methylated genes. Analysis revealed two different methylation sites corresponding to two unique genes-s100a8-cg09174555 and s100a9-cg03165378. Through the verification test of two interesting different expression positions [differentially methylated positions (DMPs)] and their corresponding gene expression, we found that methylation in these genes was negatively correlated to gene expression in the obesity group. Higher S100A8 and S100A9 expressions in obese subjects were validated in a separate microarray dataset. Conclusion: This study confirmed the relationship between DNA methylation and gene expression and emphasized the important role of S100A8 and S100A9 in the pathogenesis of obesity.

19.
Int J Gen Med ; 14: 1213-1226, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33854363

RESUMO

PURPOSE: The purpose of this study was to investigate the potential pathogenic mechanisms of post-intracerebral hemorrhage depression. METHODS: Profiles of gene expression in brain tissue of patients with intracerebral hemorrhage (ICH) or depression were downloaded from the Gene Expression Omnibus (GEO) database. We analyzed differentially expressed genes (DEGs) for the two diseases separately. With these DEGs, we conducted an enrichment analysis based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) as well as cross-talk analysis, then we identified hub bridge genes using integrated bridge landscape analysis. RESULTS: We found 131 DEGs for interaction between ICH and depression. In the enrichment analysis, we found 55 GO terms and KEGG pathways involving interacting genes of ICH and depression, and 10 GO terms and 10 KEGG pathways most significantly related to cross-talk between ICH and depression. In the integrated bridge landscape analysis, we identified 20 hub bridge genes. In further analysis, we found that hub bridge genes HLA-A, HMOX1, and JUN related to endocytosis, cell adhesion, and phagosomes may exert their effects through the dopamine (DA) system and the serotonergic pathway post-ICH depression. HLA-A may play a role in the occurrence and development of ICH and depression through immune mediation and cell adhesion. HMOX1 and JUN may participate in the mechanism by interacting with HLA-A. CONCLUSION: Through bioinformatics analysis, we identified potential hub bridge genes and pathways related to post-ICH depression. Our study provides references for further research on mechanisms on the pathogenesis of post-ICH depression.

20.
Front Psychiatry ; 12: 628361, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33708146

RESUMO

Competing endogenous RNA (ceRNA) and autophagy were related to neurological diseases. But the relationship among ceRNA, autophagy and Schizophrenia (SZ) was not clear. In this study, we obtained gene expression profile of SZ patients (GSE38484, GSE54578, and GSE16930) from Gene Expression Omnibus (GEO) database. Then we screened the autophagy-related differentially expressed lncRNA, miRNA, and mRNA (DElncRNA, DEmiRNA, and DEmRNA) combined with Gene database from The National Center for Biotechnology Information (NCBI). In addition, we performed enrichment analysis. The result showed that biological processes (BPs) mainly were associated with cellular responses to oxygen concentration. The enriched pathways mainly included ErbB, AMPK, mTOR signaling pathway and cell cycle. Furthermore, we constructed autophagy-related ceRNA network based on the TargetScan database. Moreover, we explored the diagnostic efficiency of lncRNA, miRNA and mRNA in ceRNA, through gene set variation analysis (GSVA). The result showed that the diagnostic efficiency was robust, especially miRNA (AUC = 0.884). The miRNA included hsa-miR-423-5p, hsa-miR-4532, hsa-miR-593-3p, hsa-miR-618, hsa-miR-4723-3p, hsa-miR-4640-3p, hsa-miR-296-5p, and hsa-miR-3943. The result of this study may be helpful for deepening the pathophysiology of SZ. In addition, our finding may provide a guideline for the clinical diagnosis of SZ.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...