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1.
Spectrochim Acta A Mol Biomol Spectrosc ; 258: 119847, 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33940571

RESUMO

Nondestructive instrumental identification of the green tea quality instead of professional human panel tests is highly desired for industrial application recently. The special flavor is a key quality-trait that influence consumer preference. However, flavonoids, as well as sensory-associated compounds, which play a critical role in the quality-traits profile of green tea samples have been poorly investigated. In this study, we were proposing an objective and accurate near infrared spectroscopy (NIRS) profile to support quality control within the entire green tea sensory evaluation chain, the complexity of green tea samples' sensory analysis was performed by two complementary methods: the standard calculation and the novel NIRS roadmap coupled with chemometrics. The green tea samples' physical quality, gustatory index, and nutritional index were measured respectively, which taking into consideration the gustatory evaluation of green tea for five commercially representative overall quality ("very bad", "bad", "regular", "good" and "excellent"). Our findings highlight the underexplored role of NIRS in chemical-to-sensory relationships and its widespread importance and utility in green tea quality improvement. Collectively, the comprehensive characterization of sensory-associated attribution allowed the identification of a wide array of spectrometric features, mostly related to moisture, soluble solids (SS), tea polyphenol (TPP), epigallocatechin gallate (EGCG), epicatechin (EC) and tea polysaccharide (TPS), which can be used as putative biomarkers to rapidly evaluate the green tea flavor variations related to rank differences. Otherwise, the NIRS' data were split into the calibration (n = 80) and prediction (n = 40) set independently, which showed high correlation coefficient with Rp-values of 0.9024, 0.9020 in physical and total cup quality, respectively. In this research, we demonstrated that NIRS was an easily-generated strategy and able to close the loop to feedback into the process for advanced process control. However, the established models should be improved by more green tea samples from different regions.

2.
BMC Med Inform Decis Mak ; 21(1): 147, 2021 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-33952228

RESUMO

BACKGROUND: Tongue diagnosis is an important research field of TCM diagnostic technology modernization. The quality of tongue images is the basis for constructing a standard dataset in the field of tongue diagnosis. To establish a standard tongue image database in the TCM industry, we need to evaluate the quality of a massive number of tongue images and add qualified images to the database. Therefore, an automatic, efficient and accurate quality control model is of significance to the development of intelligent tongue diagnosis technology for TCM. METHODS: Machine learning methods, including Support Vector Machine (SVM), Random Forest (RF), Gradient Boosting Decision Tree (GBDT), Adaptive Boosting Algorithm (Adaboost), Naïve Bayes, Decision Tree (DT), Residual Neural Network (ResNet), Convolution Neural Network developed by Visual Geometry Group at University of Oxford (VGG), and Densely Connected Convolutional Networks (DenseNet), were utilized to identify good-quality and poor-quality tongue images. Their performances were made comparisons by using metrics such as accuracy, precision, recall, and F1-Score. RESULTS: The experimental results showed that the accuracy of the three deep learning models was more than 96%, and the accuracy of ResNet-152 and DenseNet-169 was more than 98%. The model ResNet-152 obtained accuracy of 99.04%, precision of 99.05%, recall of 99.04%, and F1-score of 99.05%. The performances were better than performances of other eight models. The eight models are VGG-16, DenseNet-169, SVM, RF, GBDT, Adaboost, Naïve Bayes, and DT. ResNet-152 was selected as quality-screening model for tongue IQA. CONCLUSIONS: Our research findings demonstrate various CNN models in the decision-making process for the selection of tongue image quality assessment and indicate that applying deep learning methods, specifically deep CNNs, to evaluate poor-quality tongue images is feasible.

3.
J Clin Invest ; 131(9)2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33938457

RESUMO

Intestinal farnesoid X receptor (FXR) signaling is involved in the development of obesity, fatty liver disease, and type 2 diabetes. However, the role of intestinal FXR in atherosclerosis and its potential as a target for clinical treatment have not been explored. The serum levels of fibroblast growth factor 19 (FGF19), which is encoded by an FXR target gene, were much higher in patients with hypercholesterolemia than in control subjects and were positively related to circulating ceramide levels, indicating a link between intestinal FXR, ceramide metabolism, and atherosclerosis. Among ApoE-/- mice fed a high-cholesterol diet (HCD), intestinal FXR deficiency (in FxrΔIE ApoE-/- mice) or direct FXR inhibition (via treatment with the FXR antagonist glycoursodeoxycholic acid [GUDCA]) decreased atherosclerosis and reduced the levels of circulating ceramides and cholesterol. Sphingomyelin phosphodiesterase 3 (SMPD3), which is involved in ceramide synthesis in the intestine, was identified as an FXR target gene. SMPD3 overexpression or C16:0 ceramide supplementation eliminated the improvements in atherosclerosis in FxrΔIE ApoE-/- mice. Administration of GUDCA or GW4869, an SMPD3 inhibitor, elicited therapeutic effects on established atherosclerosis in ApoE-/- mice by decreasing circulating ceramide levels. This study identified an intestinal FXR/SMPD3 axis that is a potential target for atherosclerosis therapy.

4.
Chin Med J (Engl) ; 134(7): 821-828, 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33797468

RESUMO

BACKGROUND: Colorectal cancer is harmful to the patient's life. The treatment of patients is determined by accurate preoperative staging. Magnetic resonance imaging (MRI) played an important role in the preoperative examination of patients with rectal cancer, and artificial intelligence (AI) in the learning of images made significant achievements in recent years. Introducing AI into MRI recognition, a stable platform for image recognition and judgment can be established in a short period. This study aimed to establish an automatic diagnostic platform for predicting preoperative T staging of rectal cancer through a deep neural network. METHODS: A total of 183 rectal cancer patients' data were collected retrospectively as research objects. Faster region-based convolutional neural networks (Faster R-CNN) were used to build the platform. And the platform was evaluated according to the receiver operating characteristic (ROC) curve. RESULTS: An automatic diagnosis platform for T staging of rectal cancer was established through the study of MRI. The areas under the ROC curve (AUC) were 0.99 in the horizontal plane, 0.97 in the sagittal plane, and 0.98 in the coronal plane. In the horizontal plane, the AUC of T1 stage was 1, AUC of T2 stage was 1, AUC of T3 stage was 1, AUC of T4 stage was 1. In the coronal plane, AUC of T1 stage was 0.96, AUC of T2 stage was 0.97, AUC of T3 stage was 0.97, AUC of T4 stage was 0.97. In the sagittal plane, AUC of T1 stage was 0.95, AUC of T2 stage was 0.99, AUC of T3 stage was 0.96, and AUC of T4 stage was 1.00. CONCLUSION: Faster R-CNN AI might be an effective and objective method to build the platform for predicting rectal cancer T-staging. TRIAL REGISTRATION: chictr.org.cn: ChiCTR1900023575; http://www.chictr.org.cn/showproj.aspx?proj=39665.

5.
Cell Stem Cell ; 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33887179

RESUMO

The hypothalamus contains an astounding heterogeneity of neurons that regulate endocrine, autonomic, and behavioral functions. However, its molecular developmental trajectory and origin of neuronal diversity remain unclear. Here, we profile the transcriptome of 43,261 cells derived from Rax+ hypothalamic neuroepithelium to map the developmental landscape of the mouse hypothalamus and trajectory of radial glial cells (RGCs), intermediate progenitor cells (IPCs), nascent neurons, and peptidergic neurons. We show that RGCs adopt a conserved strategy for multipotential differentiation but generate Ascl1+ and Neurog2+ IPCs. Ascl1+ IPCs differ from their telencephalic counterpart by displaying fate bifurcation, and postmitotic nascent neurons resolve into multiple peptidergic neuronal subtypes. Clonal analysis further demonstrates that single RGCs can produce multiple neuronal subtypes. Our study reveals that multiple cell types along the lineage hierarchy contribute to fate diversification of hypothalamic neurons in a stepwise fashion, suggesting a cascade diversification model that deconstructs the origin of neuronal diversity.

6.
Nat Commun ; 12(1): 2288, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33863883

RESUMO

Hypothalamic tanycytes in median eminence (ME) are emerging as a crucial cell population that regulates endocrine output, energy balance and the diffusion of blood-born molecules. Tanycytes have recently been considered as potential somatic stem cells in the adult mammalian brain, but their regenerative and tumorigenic capacities are largely unknown. Here we found that Rax+ tanycytes in ME of mice are largely quiescent but quickly enter the cell cycle upon neural injury for self-renewal and regeneration. Mechanistically, Igf1r signaling in tanycytes is required for tissue repair under injury conditions. Furthermore, Braf oncogenic activation is sufficient to transform Rax+ tanycytes into actively dividing tumor cells that eventually develop into a papillary craniopharyngioma-like tumor. Together, these findings uncover the regenerative and tumorigenic potential of tanycytes. Our study offers insights into the properties of tanycytes, which may help to manipulate tanycyte biology for regulating hypothalamic function and investigate the pathogenesis of clinically relevant tumors.


Assuntos
Craniofaringioma/patologia , Células Ependimogliais/fisiologia , Eminência Mediana/fisiologia , Neoplasias Experimentais/patologia , Regeneração , Animais , Carcinogênese/patologia , Autorrenovação Celular/fisiologia , Craniofaringioma/induzido quimicamente , Craniofaringioma/genética , Proteínas do Olho/metabolismo , Feminino , Proteínas de Homeodomínio/metabolismo , Eminência Mediana/citologia , Camundongos , Neoplasias Experimentais/induzido quimicamente , Neoplasias Experimentais/genética , Proteínas Proto-Oncogênicas B-raf/genética , RNA-Seq , Receptor IGF Tipo 1/metabolismo , Transdução de Sinais , Análise de Célula Única , Fatores de Transcrição/metabolismo
7.
Toxicology ; 456: 152769, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33813002

RESUMO

Cadmium (Cd) is a nephrotoxicant that primarily damages renal proximal tubular cells. Endoplasmic reticulum (ER) stress is mechanistically linked to Cd-induced renal injury. Inositol-requiring enzyme 1 (IRE-1α) is the most conserved ER stress transducer protein, which has both kinase and endonuclease activities. This study aimed to investigate whether the two enzymatic activities of IRE-1α have different effects in its regulation of Cd-induced apoptosis. Human proximal tubular (HK-2) cells were treated with 20 µM CdCl2 for 0-24 h, and mice were fed with Cd-containing drinking water (100-400 mg/L) for 24 weeks. We found that Cd increased cell apoptosis in HK-2 cells and mouse kidneys in a time-dependent manner. Such cytotoxicity was correlated with activation of ER stress, evidenced by upregulation of IRE-1α and its target protein spliced X-box binding protein-1 (XBP-1 s). Interestingly, inhibition of IRE-1α kinase activity by KIRA6 was more protective against Cd-induced apoptosis than inhibition of its RNase activity by STF-083010. Mechanistically, Cd promoted the binding of IRE-1α with signal transducer and activator of transcription-3 (STAT3) leading to elevated phosphorylation of STAT3 at Ser727 and thus inactivation of STAT3 signaling, which resulted in aggravation of Cd-induced apoptosis in HK-2 cells. Collectively, our findings indicate that IRE-1α coordinate ER stress and STAT3 signaling in mediating Cd-induced renal toxicity, suggesting that targeting IRE-1α might be a potential therapeutic approach for Cd-induced renal dysfunction and disease.

8.
Insect Biochem Mol Biol ; 134: 103582, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33905880

RESUMO

Many insects exhibit reproductive plasticity where the photoperiod determines whether the insect becomes reproductively active or enters diapause. Adult reproductive diapause is a strategy that allows insects to survive harsh environmental conditions. A deficiency in juvenile hormone (JH) leads to reproductive diapause. However, little is known about the molecular mechanisms by which JH signaling regulates reproductive diapause. In this study, we used the cabbage beetle Colaphellus bowringi, a serious pest, to investigate the role of Krüppel homolog 1 (Kr-h1) in controlling photoperiodic plasticity of female reproduction. We focused on Kr-h1, since it acts as a key mediator of JH signaling. We show here that JH-Methoprene-tolerant signaling upregulated the expression of Kr-h1 in reproductively active C. bowringi females when reared under short day conditions. In the long day-treated diapausing females, Kr-h1 transcripts decreased dramatically. Interfering with Kr-h1 function repressed reproductive development by blocking vitellogenesis and ovarian growth. Further, Kr-h1 depletion induced other diapause-like traits, including elevated lipid accumulation and high expression of diapause-related genes. RNA-Seq showed that Kr-h1 played both activating and repressive roles, depending on whether downstream genes were acting in reproduction- or diapause pathways, respectively. Finally, we identified the DNA replication gene mini-chromosome maintenance 4 and two triacylglycerol lipase genes as critical downstream factors of Kr-h1 that are critical for reproductive plasticity in C. bowringi. These results reveal that Kr-h1 is a key component of the regulatory pathway that coordinates reproduction and diapause in insects in response to photoperiodic input.

9.
Chin Med J (Engl) ; 134(9): 1070-1078, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33883411

RESUMO

BACKGROUND: Fetal weight is an important parameter to ensure maternal and child safety. The purpose of this study was to use three-dimensional (3D) limb volume ultrasound combined with fetal abdominal circumference (AC) measurement to establish a model to predict fetal weight and evaluate its efficiency. METHODS: A total of 211 participants with single pregnancy (28-42 weeks) were selected between September 2017 and December 2018 in the Beijing Obstetrics and Gynecology Hospital of Capital Medical University. The upper arm (AVol)/thigh volume (TVol) of fetuses was measured by the 3D limb volume technique. Fetal AC was measured by two-dimensional ultrasound. Nine cases were excluded due to incomplete information or the interval between examination and delivery >7 days. The enrolled 202 participants were divided into a model group (134 cases, 70%) and a verification group (68 cases, 30%) by mechanical sampling method. The linear relationship between limb volume and fetal weight was evaluated using Pearson Chi-squared test. The prediction model formula was established by multivariate regression with data from the model group. Accuracy of the model formula was evaluated with verification group data and compared with traditional formulas (Hadlock, Lee2009, and INTERGROWTH-21st) by paired t-test and residual analysis. Receiver operating characteristic curves were generated to predict macrosomia. RESULTS: AC, AVol, and TVol were linearly related to fetal weight. Pearson correlation coefficient was 0.866, 0.862, and 0.910, respectively. The prediction model based on AVol/TVol and AC was established as follows: Y = -481.965 + 12.194TVol + 15.358AVol + 67.998AC, R2adj = 0.868. The scatter plot showed that when birth weight fluctuated by 5% (i.e., 95% to 105%), the difference between the predicted fetal weight by the model and the actual weight was small. A paired t-test showed that there was no significant difference between the predicted fetal weight and the actual birth weight (t = -1.015, P = 0.314). Moreover, the residual analysis showed that the model formula's prediction efficiency was better than the traditional formulas with a mean residual of 35,360.170. The combined model of AVol/TVol and AC was superior to the Lee2009 and INTERGROWTH-21st formulas in the diagnosis of macrosomia. Its predictive sensitivity and specificity were 87.5% and 91.7%, respectively. CONCLUSION: Fetal weight prediction model established by semi-automatic 3D limb volume combined with AC is of high accuracy, sensitivity, and specificity. The prediction model formula shows higher predictive efficiency, especially for the diagnosis of macrosomia. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03002246; https://clinicaltrials.gov/ct2/show/NCT03002246?recrs=e&cond=fetal&draw=8&rank=67.

10.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 328-332, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33812395

RESUMO

OBJECTIVE: To explore the regulation effect of myeloid leukemia No.1 Chinese herb medicine prescription combined with chemotherapy on Th17 cells in bone marrow fluid of AML patients, so as to provide guidance for improving AML treatment effect and patients' long-term survival. METHODS: Seventy patients with AML who were hospitalized in Department of Hematology, Wuwei People's Hospital from April 2017 to August 2019 were selected and enrolled in AML group, 25 healthy volunteers were selected and enrolled in control group; then according to therapeutic regimen, AML patients were divided into 2 groups: combined therapy group (myeloid leukemia NO.1 Chinese herb medicine prescription combined with chemotherapy) and non-combined therapy group (chemotherapy alone). Flow cytometry was used to detect the ratio of CD3+ CD161+ IL-17+ IFN-γ+ T cells in bone marrow fluid, and ELISA was used to detect the vascular endothelial growth factor (VEGF) and interleukin-17 (IL-17) concentrations in bone marrow fluid. Statistical analysis was performed on the data with SPSS 22.0. RESULTS: The ratio of CD3+ CD161+ IL-17+ IFN-γ+ T cells, VEGF and IL-17 concentration in newly diagnosed and relapsed AML patients were significantly higher than those in the normal control group (P<0.001); while those in CR and DFS stage patients were significantly lower than those in newly diagnosed and relapsed patients (P<0.001), and the ratio of CD3+ CD161+ IL-17+ IFN-γ+ T cells, VEGF and IL-17 concentration in DFS patients with AML were not significantly different from those in the control group (P>0.05). The ratio of CD3+ CD161+ IL-17+ IFN-γ+ T cells, VEGF and IL-17 concentration in CR stage of AML patients treated with chemotherapy alone were significantly higher than those in the control group (P<0.05), but there was no difference between combined therapy group and the control group; the ratio of CD3+ CD161+ IL-17+ IFN-γ+ T cells, the concentration of VEGF and IL-17 in CR stage of AML patients treated with chemotherapy alone were higher than those of patients treated with combined therapy regimen (P<0.05). AML patients treated with combined therapy regimen had a significantly higher complete remission rate compared with patients received chemotherapy alone (P<0.05), but the recurrence rate was significantly lower (P<0.05). CONCLUSION: Th17 cells expression in bone marrow of newly diagnoses and relapsed AML patients significantly increase, and decrease significantly after treatment. Myeloid leukemia No.1 Chinese herb prescription combined with chemotherapy can significantly increase the CR rate and reduce the RL rate for AML.


Assuntos
Leucemia Mieloide Aguda , Medicina , Medula Óssea , China , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Prescrições , Células Th17 , Fator A de Crescimento do Endotélio Vascular
11.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 395-402, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33812405

RESUMO

OBJECTIVE: To investigate the effect of etoposide (ETO) on elimination of chronic myeloid leukemia (CML) stem cells by imatinib mesylate(IM) in vivo. METHODS: SCL-tTA/BCR-ABL mice were used as CML animal model. Flow cytometry was used to assess the effect of ETO alone or in combination with IM on the number of leukemia stem cell (LSC) in bone marrow and spleen, and peripheral blood neutrophils in CML mice and normal control FVB mice. RESULTS: The results showed that in CML mice, the number and proportion of LSC in bone marrow and the proportion of neutrophils in peripheral blood decreased significantly after ETO and IM combined treatment, and the degree of decrease was more significant than that of both alone. While in wild type FVB mice, the combination of ETO and IM showed no significant effect on the number and proportion of LSK cells in bone marrow and the proportion of neutrophils in spleen. CONCLUSION: ETO can selectively enhance elimination of CML LSC by IM in vivo.


Assuntos
Resistencia a Medicamentos Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Animais , Etoposídeo , Proteínas de Fusão bcr-abl , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Camundongos , Células-Tronco
12.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(2): 428-432, 2021 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-33812410

RESUMO

OBJECTIVE: To detect the level of vascular endothelial growth factor (VEGF) in bone marrow of patients with non-M3 acute leukemia (AL), and estimate its relationship with prognosis. METHODS: From January 2016 to December 2019, 114 patients with AL in department of Hematology, Wuwei People's Hospital were selected as study group, and 25 healthy volunteers were enrolled as control group. The concentration of VEGF in bone marrow was detected by ELISA. The patients were divided into high and low concentration group according to the level of VEGF. The overall survival (OS) and event-free survival (EFS) were compared among different groups. RESULTS: The level of VEGF in patients with AL was significantly higher than that in the control group. The median OS and EFS in the low concentration group was 34.5 and 32 months, respectively, while, in the high concentration group was 30 and 26 months, respectively. The differences between the two groups were statistically significant (P=0.010). There were significant differences in OS rate (P=0.035) and EFS rate (P=0.026) between low and high concentration group. Multivariate analysis showed that high VEGF concentration was an independent risk factor affecting OS (HR=2.619, 95%CI 1.070-6.406, P=0.035) and EFS (HR=2.221, 95%CI 1.074-4.552, P=0.031) in AL patients. CONCLUSION: VEGF highly expresses in the bone marrow of patients with AL at initial diagnosis and relapse, and shows adverse effects on the prognosis.


Assuntos
Leucemia Mieloide Aguda , Fator A de Crescimento do Endotélio Vascular , Medula Óssea , Intervalo Livre de Doença , Humanos , Prognóstico
13.
Lipids Health Dis ; 20(1): 41, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33906658

RESUMO

BACKGROUND: Recently, several novel scoring systems have been developed to evaluate the severity and outcomes of acute pancreatitis. This study aimed to compare the effectiveness of novel and conventional scoring systems in predicting the severity and outcomes of acute pancreatitis. METHODS: Patients treated between January 2003 and August 2020 were reviewed. The Ranson score (RS), Glasgow score (GS), bedside index of severity in acute pancreatitis (BISAP), pancreatic activity scoring system (PASS), and Chinese simple scoring system (CSSS) were determined within 48 h after admission. Multivariate logistic regression was used for severity, mortality, and organ failure prediction. Optimum cutoffs were identified using receiver operating characteristic curve analysis. RESULTS: A total of 1848 patients were included. The areas under the curve (AUCs) of RS, GS, BISAP, PASS, and CSSS for severity prediction were 0.861, 0.865, 0.829, 0.778, and 0.816, respectively. The corresponding AUCs for mortality prediction were 0.693, 0.736, 0.789, 0.858, and 0.759. The corresponding AUCs for acute respiratory distress syndrome prediction were 0.745, 0.784, 0.834, 0.936, and 0.820. Finally, the corresponding AUCs for acute renal failure prediction were 0.707, 0.734, 0.781, 0.868, and 0.816. CONCLUSIONS: RS and GS predicted severity better than they predicted mortality and organ failure, while PASS predicted mortality and organ failure better. BISAP and CSSS performed equally well in severity and outcome predictions.

14.
BMC Med Inform Decis Mak ; 21(Suppl 1): 133, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33882934

RESUMO

BACKGROUND: MicroRNAs (miRNAs) have been confirmed to have close relationship with various human complex diseases. The identification of disease-related miRNAs provides great insights into the underlying pathogenesis of diseases. However, it is still a big challenge to identify which miRNAs are related to diseases. As experimental methods are in general expensive and time-consuming, it is important to develop efficient computational models to discover potential miRNA-disease associations. METHODS: This study presents a novel prediction method called HFHLMDA, which is based on high-dimensionality features and hypergraph learning, to reveal the association between diseases and miRNAs. Firstly, the miRNA functional similarity and the disease semantic similarity are integrated to form an informative high-dimensionality feature vector. Then, a hypergraph is constructed by the K-Nearest-Neighbor (KNN) method, in which each miRNA-disease pair and its k most relevant neighbors are linked as one hyperedge to represent the complex relationships among miRNA-disease pairs. Finally, the hypergraph learning model is designed to learn the projection matrix which is used to calculate uncertain miRNA-disease association score. RESULT: Compared with four state-of-the-art computational models, HFHLMDA achieved best results of 92.09% and 91.87% in leave-one-out cross validation and fivefold cross validation, respectively. Moreover, in case studies on Esophageal neoplasms, Hepatocellular Carcinoma, Breast Neoplasms, 90%, 98%, and 96% of the top 50 predictions have been manually confirmed by previous experimental studies. CONCLUSION: MiRNAs have complex connections with many human diseases. In this study, we proposed a novel computational model to predict the underlying miRNA-disease associations. All results show that the proposed method is effective for miRNA-disease association predication.


Assuntos
Neoplasias da Mama , Neoplasias Esofágicas , MicroRNAs , Algoritmos , Biologia Computacional , Predisposição Genética para Doença , Humanos , MicroRNAs/genética
15.
J Biomed Opt ; 26(4)2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33899380

RESUMO

SIGNIFICANCE: Corneal diseases is a major cause of reversible blindness in the world. Monitoring the progression of human corneal edema or corneal scarring to prevent the disease entering into the end stage is crucial. AIM: We present a method for sensing human corneal composition at different depths, namely focused on the epithelium and stromal layer, using high-sensitivity terahertz (THz) broadband spectroscopy. APPROACH: From the proposed methodology, the THz temporal and absorption spectra of human corneas at different edema stages have been studied. THz wave signals were collected from the direct reflection and four other collection points along the THz wave propagation direction as reviewed from the simulation THz electrical field. RESULT: Our results show that the epithelium layer acts as a good barrier to maintain hydration level of the stroma, and the quality of the epithelium can be used to predict the level of corneal swelling in corneal edema. At the detection points near to the incident point, the THz frequency spectra demonstrated interference oscillation behavior. At the final edema observing time, results showed that the epithelium lose its barrier properties. The intactness of the epithelium can be used to predict the edema severity in the final stage. When the detection points are further away from the incident point, the THz spectra are believed to contain information from stromal layer. Stromal absorption spectra demonstrated correlation with optical coherence tomography thickness results. CONCLUSION: The hydration concentration from stromal layer was further quantitatively calculated. At the end of the experiment, all the corneal hydration levels reach to the same value which shows that the edema hydration has reached maximum saturation. The information of individual sublayers of the cornea is obtained by characterizing noninvasively with the use of THz spectroscopy. To our knowledge, this is the first report of using THz for noninvasive characterization of sublayers of the cornea.

16.
Environ Pollut ; 283: 117082, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33848899

RESUMO

Chronic interstitial nephritis in agricultural communities (CINAC) has reached epidemic proportions. The combination of glyphosate and hard water has been postulated to play a potent aetiological role in CINAC. Therefore, dynamin-related protein 1 (Drp1)-mediated aberrant mitochondrial fission and subsequent activation of the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (Nlrp3)/caspase1 pathway may be involved in the pathogenesis of nephropathy. In the present study, mice were sub-chronically exposed to high doses and environmental levels of glyphosate (100 mg/kg body weight (mg/kg·bw) glyphosate in Roundup and 0.7 mg/L pure glyphosate, respectively) and hard water (2500 mg/L CaCO3 and 250 mg/L Ca2+, respectively) in drinking water. Moreover, Mdivi-1 (Md-1, 10 mg/kg·bw) was intraperitoneally injected to inhibit Drp1 on the basis of the high-dose experiment. Histopathological examination, biochemical analysis, ELISA, western blotting and fluorescent staining were used to analyse renal structure, renal tubular pyroptosis and mitochondrial fission/fusion alterations. The results showed dramatic proximal tubular injury, particularly in the combined groups. Moreover, significant increases in the protein expression levels of calmodulin (CaM), calmodulin-dependent protein kinase II (CaMKII), Drp1/p-Drp1-Ser616 and the Txnip/Nlrp3/caspase1 signalling pathway, and alterations in oxidative stress were observed in the combined groups, and these effects were attenuated by the Drp1 inhibitor Md-1. Intriguingly, there may be a synergistic effect of glyphosate and hard water on renal injury. Taken together, these results suggest that the combination of glyphosate and hard water, even at environmental exposure levels, enhances pyroptosis and ongoing tubulointerstitial inflammation through excessive Drp1-mediated mitochondrial fission.

17.
Immunotherapy ; 13(6): 527-539, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33715386

RESUMO

Objective: This study aims at investigating the safety and efficacy of immune-checkpoint inhibitors (ICIs) in patients with cancer and pre-existing autoimmune disease (AID). Materials & methods: PubMed, Embase and Cochrane Library were searched for relevant studies. The primary end points of the study were immunotoxicity and cancer response. Results: At the early use of ICIs, compared with those with active AID, grade 3-4 AID flare occurred more frequently in patients with inactive AID after treatment with ICIs; and the incidence of grade 3-4 immunotoxic effects was significantly lower in patients undergoing immunosuppressive therapy than those without corresponding treatment. In addition, patients with worsening AID generally obtained a better objective response than those without a flare. Conclusion: This study demonstrates that the toxic effects induced by immunotherapy are generally manageable in patients with cancer and pre-existing AID, some of whom even achieve satisfactory antitumor effects in clinical practice.

18.
Chin Med J (Engl) ; 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33769968

RESUMO

BACKGROUND: Epigenetics, especially DNA methylation, plays an important role in the pathogenesis of primary Sjogren syndrome (pSS). Our study aimed to reveal the role of DNA methylation in peripheral monocytes of pSS patients. METHODS: A total of 11 pSS patients and five age-matched healthy controls (HCs) were included in this study. Monocytes were isolated from peripheral blood mononuclear cells using magnetic microbeads. DNA methylation profiles were generated using Human Methylation 850K BeadChips. RESULTS: In monocytes from pSS patients, we identified 2819 differentially methylated positions (DMPs), comprising 1977 hypomethylated- and 842 hypermethylated-DMPs, corresponding to 1313 unique genes when compared with HCs. IFI44L, MX1, PAARP9, and IFITM1, which influence the interferon (IFN) signaling pathway, were among the genes hypomethylated in pSS. Functional analysis of genes with a minimum of two DMPs showed involvement in antigen binding, transcriptional regulation, cell adhesion, IFN-γ pathway, type I IFN pathway, antigen presentation, EB virus infection, human T-lymphotropic virus type 1 virus infection, and metabolic disease-related pathways. In addition, patients with higher serum IgG levels exhibited enrichment in Notch signaling and metabolic-related pathways. Upon comparing monocytes with salivary gland epithelial cells, an important overlap was observed in the cell cycle, cell senescence, and interleukin-17 signaling pathways. The differentially methylated genes were more enriched in the ribosome- and AMP-activated protein kinase signaling pathway in anti-Ro/SSA and anti-La/SSB autoantibodies double-positive patients. CONCLUSION: Genome-wide DNA methylation profiling revealed significant differences in DNA methylation in monocytes isolated from patients with pSS.

19.
Medicine (Baltimore) ; 100(11): e25130, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33725992

RESUMO

BACKGROUND: Postoperative atrial fibrillation (POAF) occurs commonly after cardiac surgery. Studies suggest that corticosteroid can reduce the incident of POAF. However, the results remain controversial. This meta-analysis aimed to evaluate the efficacy and safety corticosteroid on the prevention of POAF following cardiac surgery. METHODS: Randomized controlled trials were identified through a systematic literature search. Two investigators independently searched articles, extracted data, and assessed the quality of included studies. Primary outcome was the incidence of POAF as well as length of hospital stay and intensive care unit stay, wound and other infection, mortality, duration of ventilation, myocardial infarction, gastrointestinal complications, high blood sugar, stroke, and postoperative bleeding. RESULTS: Fourteen studies with 13,803 patients were finally involved in the present study. Overall, corticosteroid significantly decreased the risk of POAF (relative risk [RR], 0.7; 95% confidence interval [CI], 0.55-0.89; P = .003). There were no significant differences in the incidence of length of intensive care unit stay (RR, -2.32; 95% CI, -5.44 to 0.80; P = .14) and hospital stay (RR, -0.43; 95% CI, -0.84 to -0.02; P = .04), infections (RR, 1.01; 95% CI, 0.83-1.23; P = .9), mortality (RR, 0.87; 95% CI, 0.71-1.06; P = .16), duration of ventilation (RR, -0.29; 95% CI, -0.65 to 0.07; P = .12), gastrointestinal complications (RR, 1.26; 95% CI, 0.91-1.76; P = .16), high blood sugar (RR, 1.98; 95% CI, 0.91-4.31; P = .09), stroke (RR, 0.9; 95% CI, 0.69-1.18; P = .45), postoperative bleeding (RR -44.54; 95% CI, -115.28 to 26.20; P = .22) and myocardial infarction (RR, 1.71; 95% CI, 0.96-1.43; P = .12). CONCLUSION: Our review suggests that the efficacy of corticosteroid might be beneficial to POAF development in patients undergoing cardiac surgery. The strength of this association remains uncertain because of statistical and clinical heterogeneity among the included studies.


Assuntos
Corticosteroides/uso terapêutico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/prevenção & controle , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Complicações Pós-Operatórias , Idoso , Feminino , Humanos , Incidência , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Risco , Fatores de Tempo , Resultado do Tratamento
20.
Ann Palliat Med ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33691433

RESUMO

BACKGROUND: The aim of this study was to explore the impact of chemotherapy (CT) and chemoradiotherapy (CRT) on prognosis in metastatic esophageal cancer (mEC) patients. METHODS: Information of patients with mEC from 2010 to 2016 was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Demographic and clinical data between CT and CRT groups were compared. Propensity score matching (PSM) analysis was used to reduce the influence of potential confounding factors. Multivariate Cox regression analysis was used to evaluate prognostic factors. Moreover, interaction tests and survival analyses were performed to determine whether pathological type conferred any survival benefits in subgroups. RESULTS: A total of 3,352 mEC patients were recruited including 1,697 CT patients and 1,655 CRT patients. In multivariable Cox regression, marital status, gender and pathological type were identified as independent prognostic factors for mEC. There was no statistical significance between the CT group and CRT group in overall survival (OS) and cancer-specific survival (CSS) in the matched and unmatched cohort. In subgroup analyses, patients with esophageal adenocarcinoma (EAC) undergoing CT had favorable prognosis. However, in the subgroup of esophageal squamous cell carcinoma (ESCC), patients in the CT group had worse outcomes compared with patients in the CRT group. CONCLUSIONS: Patients with EAC and ESCC could respectively benefit from CT and CRT. Besides, we recommend individualizing the treatment strategy for mEC based on the pathological type.

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