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1.
Front Genet ; 13: 875128, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35559013

RESUMO

Objective: This study used homologous recombination (HR) related signatures to develop a clinical prediction model for screening immune checkpoint inhibitors (ICIs) advantaged populations and identify hub genes in advanced metastatic urothelial carcinoma. Methods: The single-sample gene enrichment analysis and weighted gene co-expression network analysis were applied to identify modules associated with immune response and HR in IMvigor210 cohort samples. The principal component analysis was utilized to determine the differences in HR-related module gene signature scores across different tissue subtypes and clinical variables. Risk prediction models and nomograms were developed using differential gene expression analysis associated with HR scores, least absolute shrinkage and selection operator, and multivariate proportional hazards model regression. Additionally, hub genes were identified by analyzing the contribution of HR-related genes to principal components and overall survival analysis. Finally, clinical features from GSE133624, GSE13507, the TCGA, and other data sets were analyzed to validate the relationship between hub genes and tumor growth and mutation. Results: The HR score was significantly higher in the complete/partial response group than in the stable/progressive disease group. The majority of genes associated with HR were discovered to be involved in the cell cycle and others. Genomically unstable, high tumor level, and high immune level samples all exhibited significantly higher HR score than other sample categories, and higher HR scores were related to improved survival following ICIs treatment. The risk scores for AUNIP, SEPT, FAM72D, CAMKV, CXCL9, and FOXN4 were identified, and the training and verification groups had markedly different survival times. The risk score, tumor neoantigen burden, mismatch repair, and cell cycle regulation were discovered to be independent predictors of survival time following immunotherapy. Patients with a high level of expression of hub genes such as EME1, RAD51AP1, and RAD54L had a greater chance of surviving following immunotherapy. These genes are expressed at significantly higher levels in tumors, high-grade cancer, and invasive cancer than other categories, and are associated with TP53 and RB1 mutations. Conclusion: HR-related genes are upregulated in genomically unstable samples, the survival time of mUC patients after treatment with ICIs can be predicted using a normogram model based on HR signature.

2.
Food Funct ; 13(9): 5416-5429, 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35475434

RESUMO

Herein, we assessed the effects of Lycium barbarum oligosaccharides (LBO) on the intestinal microenvironment of a type 2 diabetes (T2D) mouse model through gut microbiome and metabolomics analysis. We set high (300 mg kg-1), medium (200 mg kg-1), and low (100 mg kg-1) doses of LBO for intervention once a day for 4 weeks. The results showed that the intervention effect of the medium-dose group was the most significant. It reduced the symptoms of hyperglycemia, inflammation, insulin resistance, and lipid accumulation in the T2D mouse model. It restored the structure of damaged tissues and cells, such as the pancreas, liver, and kidneys. LBO increased the relative abundance of beneficial bacteria, such as Lactobacillus, Bacteroides, Prevotella, and Akkermansia, and maintained intestinal barrier integrity. The faecal metabolic map showed that the contents of glycogen amino acids, such as proline, serine, and leucine, increased. The contents of cholic, capric, and dodecanoic acid decreased. In summary, we may suggest that LBO can be used as a prebiotic for treating T2D.


Assuntos
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Lycium , Animais , Biologia Computacional , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/microbiologia , Glicolipídeos/farmacologia , Lycium/química , Metabolômica , Camundongos , Oligossacarídeos/farmacologia
3.
Int J Gen Med ; 15: 325-342, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35035230

RESUMO

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is a commonly occurring tumor. Through a deeper understanding of the immune regulatory mechanisms in the tumor microenvironment, immunotherapy may serve as a potential treatment for cancer patients. This study aimed at identifying the survival-related immune cells and hub genes, which could be potential targets for immunotherapy in ccRCC. METHODS: The gene expression profiles and clinical data of ccRCC patients were extracted from UCSC Xena and Gene Expression Omnibus (GEO) databases. Kaplan-Meier (KM) survival and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were utilized to select the survival-related tumor-infiltrating immune cells. Multivariate Cox regression was utilized to develop a signature based on the tumor-infiltrating immune cells (TIICs). Based on the signature, the risk score was calculated, following which the samples were divided into high-risk and low-risk groups. Differentially expressed genes (DEGs) between the two risk groups were identified. Functional enrichment analysis was performed and cytoHubba plug-in of Cytoscape was used to identify the hub genes. Multiple datasets were utilized to validate these hub genes, including the Gene Expression Profiling Interactive Analysis (GEPIA), UALCAN, and the Human Protein Atlas (HPA), and the GEO datasets. Finally, a correlation analysis was performed to evaluate the relationship between the hub genes and TIICs. RESULTS: Four immune survival-related cells, including T cell CD4 memory-activated, T cell regulatory (Tregs), eosinophils, and mast cell resting were identified. Nine immune-specific hub genes were identified, which included APOE, CASR, CTLA4, CXCL8, EGF, F2, KNG1, MMP9, and IL6. Furthermore, these hub genes were significantly correlated with clinical traits and closely associated with some TIICs. CONCLUSION: A total of four survival-related immune cell types and nine hub genes were found to be closely associated with ccRCC. These findings may have implications for the development of novel potential immunotherapeutic targets for ccRCC.

4.
Neuro Oncol ; 2022 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-35100427

RESUMO

BACKGROUND: Accurate detection is essential for brain metastasis (BM) management, but manual identification is laborious. This study developed, validated, and evaluated a BM detection (BMD) system. METHODS: Five hundred seventy-three consecutive patients (10,448 lesions) with newly diagnosed BMs and 377 patients without BMs were retrospectively enrolled to develop a multi-scale cascaded convolutional network using 3D-enhanced T1-weighted MR images. BMD was validated using a prospective validation set comprising an internal set (46 patients with 349 lesions; 44 patients without BMs) and three external sets (102 patients with 717 lesions; 108 patients without BMs). The lesion-based detection sensitivity and the number of false positives (FPs) per patient were analyzed. The detection sensitivity and reading time of three trainees and three experienced radiologists from three hospitals were evaluated using the validation set. RESULTS: The detection sensitivity and FPs were 95.8% and 0.39 in the test set, 96.0% and 0.27 in the internal validation set, and ranged from 88.9% to 95.5% and 0.29 to 0.66 in the external sets. The BMD system achieved higher detection sensitivity (93.2% [95% CI, 91.6-94.7%]) than all radiologists without BMD (ranging from 68.5% [95% CI, 65.7-71.3%] to 80.4% [95% CI, 78.0-82.8%], all P < 0.001). Radiologist detection sensitivity improved with BMD, reaching 92.7% to 95.0%. The mean reading time was reduced by 47% for trainees and 32% for experienced radiologists assisted by BMD relative to that without BMD. CONCLUSIONS: BMD enables accurate BM detection. Reading with BMD improves radiologists' detection sensitivity and reduces their reading times.

5.
Food Chem ; 377: 131995, 2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34990944

RESUMO

Here, a cinnamaldehyde essential oil (CEO)/ß-Cyclodextrin (ß-CD) composite with a high embedding rate (91.74 ± 0.82%) was prepared. Its structure was characterized by Fourier transform infrared spectrometer (FT-IR) and X-ray diffractometer (XRD). Pickering emulsions prepared by ß-CD and CEO/ß-CD at different concentrations (1-5%) were comparatively investigated. The CEO/ß-CD emulsions had better storage stability. Rheological results confirmed the emulsions were all gel-like elastic emulsions and had shear thinning phenomenon. Fluorescence microscopy and scanning electron microscopy (SEM) results confirmed that the most of excessive ß-CD was adsorbed on the surface of emulsion droplets as crystals, formed thick protective shell in ß-CD emulsions, while the most of excessive composites were distributed in the aqueous phase forming a stable network structure in CEO/ß-CD emulsions. It caused these two emulsions had different rheological properties, and different changing trends in droplet size.


Assuntos
Óleos Voláteis , beta-Ciclodextrinas , Acroleína/análogos & derivados , Emulsões , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier
6.
Med Oncol ; 39(4): 41, 2022 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-35092501

RESUMO

The tumor immune microenvironment (TIME) and N6-methyladenosine (m6A) are related to the progression of several types of cancer. Nevertheless, the impact of m6A on the TIME of clear cell renal cell carcinoma (ccRCC) remains unclear. This study used an unsupervised clustering algorithm to divide the samples into distinct subgroups. The single sample gene set enrichment analysis (ssGSEA) algorithm to estimate the TIME. The correlation between m6A regulators and immune cells in different subgroups was calculated using Spearman analysis. At last, the relationship between IGF2BP2 and HMGA2 was validated in several datasets, including TCGA-KIRC, GEO, and HPA datasets. We found that m6A regulators were differently expressed in several clinical groups. Based on the expression of m6A regulators, we divided the samples into three subgroups. Then, the survival analysis for these three subgroups showed that the cluster 2 subgroup had poor overall survival (OS). Further, we found that IGF2BP2 and IGF2BP3 were essential components in the cluster 2 subgroup using the principal component analysis (PCA) algorithm. In addition, the expression of these two genes was significantly correlated with survival time. At last, we found that HMGA2 was significantly correlated with IGF2BP2 in several datasets, which indicated that HMGA2 is an essential role in affecting IGF2BP2 regulating the TIME. There is a close correlation between m6A regulators and TIME. Moreover, IGF2BP2 is related to the progression of ccRCC and plays an essential role in affecting the TIME.


Assuntos
Adenosina/análogos & derivados , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , Microambiente Tumoral/genética , Adenosina/genética , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica , Proteína HMGA2/genética , Humanos , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Prognóstico , Proteínas de Ligação a RNA/genética , Análise de Sobrevida , Transcriptoma , Microambiente Tumoral/imunologia
8.
Front Mol Biosci ; 9: 806727, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35495630

RESUMO

Background: Telomerase reverse transcriptase promoter (TERT-p) mutation has been frequently found, but associated with contrary prognosis, in both low-grade gliomas and glioblastomas. For the low-grade gliomas (Grades II-III), TERT-p mutant patients have a better prognosis than the wildtype patients, whereas for the GBMs (Grade IV), TERT-p mutation is related to a poor prognosis. We hypothesize that there exist high-risk patients in LGGs who share GBM-like molecular features, including TERT-p mutation, and need more intensive treatment than other LGGs. A molecular signature is needed to identify these high-risk patients for an accurate and timely treatment. Methods: Using the within-sample relative expression orderings of gene pairs, we identified the gene pairs with significantly stable REOs, respectively, in both the TERT-p mutant LGGs and GBMs but with opposite directions in the two groups. These reversely stable gene pairs were used as the molecular signature to stratify the LGGs into high-risk and low-risk groups. Results: A signature consisting of 21 gene pairs was developed, which can classify LGGs into two groups with significantly different overall survival. The high-risk group has a similar genetic mutation profile and a similar survival profile as GBMs, and these high-risk tumors may progress to a more malignant state. Conclusion: The 21 gene-pair signature based on REOs is capable of identifying high-risk patients in LGGs and guiding the clinical choice for appropriate and timely intervention.

9.
Sci Total Environ ; 804: 150071, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34509855

RESUMO

In this study, a lipid degrading microbe consortium (LDMC) was assembled to improve the performance of activated sludge (AS) on cooking wastewater purification. LDMC can rapidly degrade high-level oil (efficiency beyond 93.0% at 5.0 g/L) as sole carbon source under various environmental conditions (10.0-45.0 °C, pH 2.0-12.0). With LDMC inoculation, AS' water treatment performance was significantly enhanced, which removed 36.10 and 48.93% more chemical oxygen demand (COD) and ammonia nitrogen from wastewater than control. A better settling property and smaller bulking risk were found with LDMC inoculation, indicated by a lower SV30 and SVI index but a higher MLSS. By GC/MS analysis, a gradual degradation on the end of the fatty acid chain was suggested. LDMC inoculation significantly changed AS's microbial community structure, improved its stability, decreased the microbial community diversity, facilitated the enrichment of lipid degraders and functional genes related to lipid bio-degradation. Lipid degraders including Nakamurella sp. and Stenotrophomona sp., etc. played a crucial role during oil degradation. Sludge structure maintainers such as Kineosphaera sp. contributed largely to the stability of AS under exogenous stress. This study provided an efficient approach for cooking wastewater treatment along with the underlying mechanism exploration, which should give insights into oil-containing environmental remediation.


Assuntos
Esgotos , Purificação da Água , Reatores Biológicos , Culinária , Lipídeos , Águas Residuárias
10.
Crit Rev Food Sci Nutr ; : 1-19, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34872394

RESUMO

Biopolymeric films manufactured from materials such as starch, cellulose, protein, chitosan, gelatin, and polyvinyl alcohol are widely applied due to their complete biodegradability. While biopolymer-based films exhibit good gas barriers and optical properties when used in packaging, poor moisture resistance and mechanical properties limit their further application. Ultrasonication is a promising, effective technology for resolving these shortcomings, with its high efficiency, environmentally friendly nature, and safety. This review briefly introduces basic ultrasonication principles and their main effects on mechanical properties, transparency, color, microstructure, water vapor permeability, and oxygen resistance. We also describe the thermal performance of biopolymeric films. While ultrasonication has many positive effects on the physicochemical properties of biopolymeric films, many factors influence their behavior during film preparation, including power density, amplitude, treatment time, frequency, and the inherent properties of the source materials. This review focuses on biopolymers as film-forming materials and comprehensively discusses the promotional effects of ultrasonication on their physicochemical properties.

11.
Heart Surg Forum ; 24(6): E1023-E1026, 2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34962466

RESUMO

BACKGROUND: Cardiac paragangliomas are rare neuroendocrine tumors that will cause significant morbidity if left undiagnosed. Because of the paucity of cohort data, their rapid diagnosis and appropriate management still pose unique challenges to cardiac surgeons. We aimed to investigate the clinical features and surgical management of primary cardiac paragangliomas in our single center. METHODS: From May 2014 to October 2020, patients diagnosed with primary cardiac paragangliomas retrospectively were reviewed. Demographic data, clinical presentation, preoperative imaging methods, surgical resection, perioperative management, histological analysis, and outcomes were recorded. Postoperative follow up also was reviewed. RESULTS: With multiple imaging methods, including echocardiography, computed tomography, positron-emission tomographic-computed tomography, and biochemical tests, there were five cases of primary cardiac paraganglioma verified by postoperative immunohistochemical staining, two of which were hormonally active. There were no metastatic cardiac paragangliomas, according to positron-emission tomographic-computed tomography, and all patients accepted surgical treatment. Preoperative adrenoceptor blockade was given to hormonally active patients, accordingly. Complete resection of the tumor was accomplished under cardiopulmonary bypass in each case. Tumor distribution included two masses on the roof of the left atrium, two masses in the right atrioventricular groove, and one between the ascending aorta and main pulmonary artery. Immunohistochemical staining for chromogranin, neuron-specific enolase, synaptophysin, and S-100 were positive, which were typical of cardiac paraganglioma. There were no operative deaths. All the patients had an uneventful recovery except one patient who underwent low cardiac output syndrome. During follow up (mean 4.2 years, range 0.6-7.0 years), all patients were well with New York Heart Association class I or II. Only one patient developed thyroid carcinoma three years after surgery but with no paraganglioma recurrence during periodic computed tomography, and this patient recovered well after thyroidectomy. CONCLUSION: Although cardiac paragangliomas are rare and may present surgical challenges for clinicians, surgical resection remains the choice of treatment with favorable outcomes through a multidisciplinary heart team. Moreover, lifelong surveillance still is recommended to detect possible recurrence or associated nonchromaffin tumors in time.


Assuntos
Neoplasias Cardíacas/cirurgia , Paraganglioma Extrassuprarrenal/cirurgia , Adulto , Biomarcadores Tumorais/análise , Feminino , Seguimentos , Neoplasias Cardíacas/diagnóstico por imagem , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Paraganglioma Extrassuprarrenal/diagnóstico por imagem , Assistência Perioperatória , Estudos Retrospectivos , Resultado do Tratamento
12.
J Healthc Eng ; 2021: 2680526, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34795881

RESUMO

Introduction: We aimed to evaluate whether circulating tumor cells (CTCs) were the prognostic indicator responsible for chemotherapy and survival of NSCLC patients. Methods: Between January 2013 and September 2017, CTCs in the peripheral blood of histologically confirmed stages III and IV NSCLC patients were collected. Blood specimens were obtained on the first day of treatment, chemotherapy 2 and 4 cycles, or targeted therapy 1 and 2 months for CTCs detection. The positive CTC status was defined as one or more CTCs per 7.5 ml. Results: 100 patients were enrolled, of which 48 patients (48%) were identified to be CTC positive at baseline. A higher CTC-positive rate was observed in stage IV NSCLC patients than stage III patients (69% vs. 40%, P=0.015). CTC cluster was significantly correlated with disease control rate. Based on the baseline CTC number, patients were divided into low CTC levels (<4 CTCs, LL) and high CTC levels (≥4 CTCs, HL). There was clinically significant shorter median OS and OS (overall survival) and PFS (progression-free survival) in HL group patients (P < 0.001). Conclusions: The positive association between the CTC number and survival suggested that the baseline CTC number and changes during treatment might be the prognostic information of response rate and overall survival in Chinese patients suffering stage III/IV NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Células Neoplásicas Circulantes , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Prognóstico
13.
Exp Ther Med ; 22(5): 1260, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34603528

RESUMO

Rheumatoid arthritis (RA) is a chronic, progressive and systemic autoimmune disease mainly characterized by symmetric multijoint synovitis. Quercetin has anti-inflammatory, anti-oxidation and immune regulation activities, and therefore shows high medicinal value. The present study aimed to observe the effect of quercetin on fibroblast-like synoviocytes (FLSs) in RA. Rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) were pretreated with 50 nmol/l quercetin for 2 h and were then stimulated using TNF-α for 24 h for subsequent experiments. RAFLSs were transfected with short interfering (si)-X-inactive specific transcript (XIST), microRNA (miR)-485 mimic, miR-485 inhibitor or si-PSMB8 or combination. ELISA, PCR and western blotting was used to evaluate the effect of quercetin on RAFLSs treated with TNF-α. It was revealed that quercetin inhibited the production of inflammatory cytokines and the expression of XIST in RAFLSs induced by TNF-α. Bioinformatics analysis indicated that XIST acted as a sponge for miR-485 and that proteasome subunit ß type-8 (PSMB8) was a direct target of miR-485. Moreover, PSMB8 functioned as a suppressor in inflammatory cytokine production of RAFLSs induced by TNF-α. Overall, quercetin was observed to inhibit the production of inflammatory cytokines and the expression of XIST in RAFLSs induced by TNF-α. Moreover, XIST-silencing could suppress the inflammatory reaction by sponging miR-485 in cells treated with TNF-α. Altogether, quercetin could suppress the development of RA in vitro.

14.
J Clin Lab Anal ; 35(11): e24022, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34606125

RESUMO

BACKGROUND: Immunotherapeutic approaches have recently emerged as effective treatment regimens against various types of cancer. However, the immune-mediated mechanisms surrounding papillary renal cell carcinoma (pRCC) remain unclear. This study aimed to investigate the tumor microenvironment (TME) and identify the potential immune-related biomarkers for pRCC. METHODS: The CIBERSORT algorithm was used to calculate the abundance ratio of immune cells in each pRCC samples. Univariate Cox analysis was used to select the prognostic-related tumor-infiltrating immune cells (TIICs). Multivariate Cox regression analysis was performed to develop a signature based on the selected prognostic-related TIICs. Then, these pRCC samples were divided into low- and high-risk groups according to the obtained signature. Analyses using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) were performed to investigate the biological function of the DEGs (differentially expressed genes) between the high- and low-risk groups. The hub genes were identified using a weighted gene co-expression network analysis (WGCNA) and a protein-protein interaction (PPI) analysis. The hub genes were subsequently validated by multiple clinical traits and databases. RESULTS: According to our analyses, nine immune cells play a vital role in the TME of pRCC. Our analyses also obtained nine potential immune-related biomarkers for pRCC, including TOP2A, BUB1B, BUB1, TPX2, PBK, CEP55, ASPM, RRM2, and CENPF. CONCLUSION: In this study, our data revealed the crucial TIICs and potential immune-related biomarkers for pRCC and provided compelling insights into the pathogenesis and potential therapeutic targets for pRCC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais , Neoplasias Renais , Microambiente Tumoral/imunologia , Algoritmos , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/diagnóstico , Neoplasias Renais/imunologia , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Linfócitos do Interstício Tumoral/imunologia , Mapas de Interação de Proteínas/genética
15.
J Int Med Res ; 49(9): 3000605211041265, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34551599

RESUMO

OBJECTIVE: To compare the sternal fixation effect of a polyetheretherketone (PEEK) cable product and stainless steel wire after median sternotomy. METHODS: A multicentre retrospective clinical trial was conducted in patients that underwent median sternotomy for a range of surgical reasons. The sternum was fixed using PEEK sternal cables in the experimental group and stainless steel wires in the control group. The general patient state, product manoeuvrability, bone and wound healing state and blood test results were evaluated at seven visits during the preoperative, surgical and follow-up periods. RESULTS: A total of 108 patients (54 in each group) were included in the analysis at the final 180-day follow-up. The sternum was successfully closed using PEEK cables or steel wires in all patients and all healed well. No pathological changes were found on the X-ray imaging. Computed tomography imaging confirmed ideal fracture healing. No significant difference was found between the experimental group and the control group in outcomes. CONCLUSION: PEEK cables are easy to implant and show desirable effectiveness in sternal fixation without any observed side-effects.


Assuntos
Aço Inoxidável , Esternotomia , Benzofenonas , Fios Ortopédicos , Humanos , Polímeros , Estudos Retrospectivos , Esterno/diagnóstico por imagem , Esterno/cirurgia
16.
J Med Genet ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544842

RESUMO

BACKGROUND: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers. METHODS: A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed. FINDINGS: 155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition. CONCLUSIONS: Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

17.
BMC Cancer ; 21(1): 858, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315402

RESUMO

BACKGROUND: Bladder cancer (BC) is a common malignancy neoplasm diagnosed in advanced stages in most cases. It is crucial to screen ideal biomarkers and construct a more accurate prognostic model than conventional clinical parameters. The aim of this research was to develop and validate an mRNA-based signature for predicting the prognosis of patients with bladder cancer. METHODS: The RNA-seq data was downloaded from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were screened in three datasets, and prognostic genes were identified from the training set of TCGA dataset. The common genes between DEGs and prognostic genes were narrowed down to six genes via Least Absolute Shrinkage and Selection Operator (LASSO) regression, and stepwise multivariate Cox regression. Then the gene-based risk score was calculated via Cox coefficient. Time-dependent receiver operating characteristic (ROC) and Kaplan-Meier (KM) survival analysis were used to assess the prognostic power of risk score. Multivariate Cox regression analysis was applied to construct a nomogram. Decision curve analysis (DCA), calibration curves, and time-dependent ROC were performed to assess the nomogram. Finally, functional enrichment of candidate genes was conducted to explore the potential biological pathways of candidate genes. RESULTS: SORBS2, GPC2, SETBP1, FGF11, APOL1, and H1-2 were screened to be correlated with the prognosis of BC patients. A nomogram was constructed based on the risk score, pathological stage, and age. Then, the calibration plots for the 1-, 3-, 5-year OS were predicted well in entire TCGA-BLCA patients. Decision curve analysis (DCA) indicated that the clinical value of the nomogram was higher than the stage model and TNM model in predicting overall survival analysis. The time-dependent ROC curves indicated that the nomogram had higher predictive accuracy than the stage model and risk score model. The AUC of nomogram time-dependent ROC was 0.763, 0.805, and 0.806 for 1-year, 3-year, and 5-year, respectively. Functional enrichment analysis of candidate genes suggested several pathways and mechanisms related to cancer. CONCLUSIONS: In this research, we developed an mRNA-based signature that incorporated clinical prognostic parameters to predict BC patient prognosis well, which may provide a novel prognosis assessment tool for clinical practice and explore several potential novel biomarkers related to the prognosis of patients with BC.


Assuntos
Biomarcadores Tumorais , Transcriptoma , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/mortalidade , Bases de Dados Genéticas , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Mutação , Estadiamento de Neoplasias , Nomogramas , Prognóstico , RNA Mensageiro , Curva ROC , Reprodutibilidade dos Testes , Neoplasias da Bexiga Urinária/patologia
18.
Environ Pollut ; 288: 117753, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34261028

RESUMO

Indoor air quality is critically important to the human as people spend most time indoors. Indoor PM2.5 is related to the outdoor levels, but more directly influenced by internal sources. Severe household air pollution from solid fuel use has been recognized as one major risk for human health especailly in rural area, however, the issue is significantly overlooked in most national air quality controls and intervention policies. Here, by using low-cost sensors, indoor PM2.5 in rural homes burning coals was monitored for ~4 months and analyzed for its temporal dynamics, distributions, relationship with outdoor PM2.5, and quantitative contributions of internal sources. A bimodal distribution of indoor PM2.5 was identified and the bimodal characteristic was more significant at the finer time resolution. The bimodal distribution maxima were corresponding to the emissions from strong internal sources and the influence of outdoor PM2.5, respectively. Indoor PM2.5 was found to be correlated with the outdoor PM2.5, even though indoor coal combustion for heating was thought to be predominant source of indoor PM2.5. The indoor-outdoor relationship differed significantly between the heating and non-heating seasons. Impacts of typical indoor sources like cooking, heating associated with coal use, and smoking were quantitatively analyzed based on the highly time-resolved PM2.5. Estimated contribution of outdoor PM2.5 to the indoor PM2.5 was ~48% during the non-heating period, but decreased to about 32% during the heating period. The contribution of indoor heating burning coals comprised up to 47% of the indoor PM2.5 during the heating period, while the other indoor sources contributed to ~20%. The study, based on a relatively long-term timely resolved PM2.5 data from a large number of rural households, provided informative results on temporal dynamics of indoor PM2.5 and quantitative contributions of internal sources, promoting scientific understanding on sources and impacts of household air pollution.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Carvão Mineral , Monitoramento Ambiental , Humanos , Material Particulado/análise
19.
Cancer Med ; 10(15): 5375-5391, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34165261

RESUMO

The emergence of immunotherapy has provided an option of treatment methods for bladder cancer (BC). However, the beneficiaries of immunotherapy are still limited to small-scale patients, and immunotherapy-related adverse events often occur. It is a major challenge for clinical work to study the immune subtypes of BC and the molecular mechanism of immune escape, and identify the immune responders accurately. Here, we explore the immune molecular subtypes of bladder cancer and potential escape mechanisms. First, we screened the expression profiles of 303 differentially expressed immune-related genes in BC patients from the Cancer Genome Atlas (TCGA) database, and successfully identified 4 molecular subtypes of BC. By comparing the clinical characteristics, immune cells infiltration, the expression of checkpoint genes, human leukocyte antigen (HLA) genes, and gene mutation status of different subtypes, we identified different clinical and immunological characteristics of 4 subtypes. Among 4 subtypes, Cluster 2 met the general characteristics of immunotherapy responders and responded well to immunotherapy, while Cluster 4 had the highest expression of immune characteristics, and is similar to the immune environment of normal bladder tissue. Then, the weighted gene co-expression network analysis (WGCNA) of immune-related genes revealed that brown module was positively correlated with subtypes. Pathway enrichment analysis explored the major pathways associated with subtypes, which are also associated with immune escape mechanisms. Moreover, the decision tree model, which was constructed by the principle of random forest screening factors, was also validated in internal validation set and external validation set from the Gene Expression Omnibus (GEO) cohort (GSE133624), and could achieve accurate subtypes prediction for BC patients with high-throughput sequencing. Taken together, we explored the immune molecular subtypes and their mechanisms of BC, and these results may provide guidance for the development of new BC immunotherapy strategies.


Assuntos
Imunoterapia , Evasão Tumoral/imunologia , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/terapia , Bases de Dados Genéticas , Árvores de Decisões , Perfilação da Expressão Gênica , Genes cdc , Antígenos HLA/genética , Humanos , Imunidade Celular , Imunoterapia/efeitos adversos , Mutação , Reprodutibilidade dos Testes , Resultado do Tratamento , Evasão Tumoral/genética , Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/genética
20.
Oral Oncol ; 118: 105335, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34023742

RESUMO

OBJECTIVES: We aimed to build a survival system by combining a highly-accurate machine learning (ML) model with explainable artificial intelligence (AI) techniques to predict distant metastasis in locoregionally advanced nasopharyngeal carcinoma (NPC) patients using magnetic resonance imaging (MRI)-based tumor burden features. MATERIALS AND METHODS: 1643 patients from three hospitals were enrolled according to set criteria. We employed ML to develop a survival model based on tumor burden signatures and all clinical factors. Shapley Additive exPlanations (SHAP) was utilized to explain prediction results and interpret the complex non-linear relationship among features and distant metastasis. We also constructed other models based on routinely used cancer stages, Epstein-Barr virus (EBV) DNA, or other clinical features for comparison. Concordance index (C-index), receiver operating curve (ROC) analysis and decision curve analysis (DCA) were executed to assess the effectiveness of the models. RESULTS: Our proposed system consistently demonstrated promising performance across independent cohorts. The concordance indexes were 0.773, 0.766 and 0.760 in the training, internal validation and external validation sets. SHAP provided personalized protective and risk factors for each NPC patient and uncovered some novel non-linear relationships between features and distant metastasis. Furthermore, high-risk patients who received induction chemotherapy (ICT) and concurrent chemoradiotherapy (CCRT) had better 5-year distant metastasis-free survival (DMFS) than those who only received CCRT, whereas ICT + CCRT and CCRT had similar DMFS in low-risk patients. CONCLUSIONS: The interpretable machine learning system demonstrated superior performance in predicting metastasis in locoregionally advanced NPC. High-risk patients might benefit from ICT.


Assuntos
Infecções por Vírus Epstein-Barr , Aprendizado de Máquina , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Quimiorradioterapia , Herpesvirus Humano 4 , Humanos , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/terapia , Neoplasias Nasofaríngeas/diagnóstico , Neoplasias Nasofaríngeas/terapia , Prognóstico , Carga Tumoral
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