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1.
Artigo em Inglês | MEDLINE | ID: mdl-31619447

RESUMO

OBJECTIVE: To describe the detailed clinical characteristics, immunotherapy, and long-term outcomes of patients with anti-NMDA receptor (NMDAR) encephalitis in China. METHODS: A single-center, prospective study. Patients who met the diagnostic criteria were enrolled from 2011 to 2017 and followed up. The clinical features, treatment, and long-term outcomes were collected prospectively. Factors affecting the long-term prognosis were analyzed. RESULTS: The study included 220 patients. The most common clinical presentations were psychosis (82.7%) and seizures (80.9%). Of the patients, 19.5% had an underlying neoplasm; of which ovarian teratoma was 100% of tumors in females and only one male had lung cancer. Most patients (99.5%) received first-line therapy (glucocorticoids, IV immunoglobulin, or plasmapheresis alone or combined), and only 7.3% received second-line immunotherapy (rituximab, cyclophosphamide alone, or combined). Long-term immunotherapy (mycophenolate mofetil or azathioprine >1 year) was administered to 53.2% of patients. During the first 12 months, 207 (94.1%) patients experienced improvement, and 5 (2.3%) died, whereas 38 (17.3%) experienced relapses. At 12-month follow-up, 92.7% had favorable clinical outcomes (modified Rankin Scale score ≤2). CONCLUSIONS: Patients in China present with psychosis and seizure frequently but have a low percentage of underlying neoplasms. Re-enforced first-line immunotherapy is effective in managing anti-NMDAR encephalitis in the acute phase. Although relapse is relatively common, with combined first-line and long-term immunotherapy, most patients reached favorable outcomes.

2.
Comput Med Imaging Graph ; 79: 101660, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31785402

RESUMO

Precise 3D segmentation of infant brain tissues is an essential step towards comprehensive volumetric studies and quantitative analysis of early brain development. However, computing such segmentations is very challenging, especially for 6-month infant brain, due to the poor image quality, among other difficulties inherent to infant brain MRI, e.g., the isointense contrast between white and gray matter and the severe partial volume effect due to small brain sizes. This study investigates the problem with an ensemble of semi-dense fully convolutional neural networks (CNNs), which employs T1-weighted and T2-weighted MR images as input. We demonstrate that the ensemble agreement is highly correlated with the segmentation errors. Therefore, our method provides measures that can guide local user corrections. To the best of our knowledge, this work is the first ensemble of 3D CNNs for suggesting annotations within images. Our quasi-dense architecture allows the efficient propagation of gradients during training, while limiting the number of parameters, requiring one order of magnitude less parameters than popular medical image segmentation networks such as 3D U-Net (Çiçek, et al.). We also investigated the impact that early or late fusions of multiple image modalities might have on the performances of deep architectures. We report evaluations of our method on the public data of the MICCAI iSEG-2017 Challenge on 6-month infant brain MRI segmentation, and show very competitive results among 21 teams, ranking first or second in most metrics.

3.
J Hazard Mater ; : 121663, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31784133

RESUMO

Exposure to polycyclic aromatic hydrocarbons and phthalates are linked to lung function decline and altered relative telomere length (RTL) accompanying with oxidative stress and inflammatory events in human body. However, limited data are available about impacts of co-exposure of PAHs and phthalates on lung function and RTL. We conducted a pilot study with repeated measures during the winter of 2014 and summer of 2015 in Wuhan city, China. Participants took part in the measures of lung function, RTL, urinary monohydroxylated-PAHs (OH-PAHs) and phthalate metabolites over three consecutive days in each season. Linear mixed-effect (LME) models and Bayesian kernel machine regression (BKMR) were used to analyze the relations of OH-PAHs or phthalate metabolites with lung function or RTL. LME models showed the negative associations of 3-day average of hydroxyphenanthrene (2 + 3-, 4-OHPhe) or 1-hydroxypyrene with FEV1, 3-day average of 2 + 3-OHPhe with FVC. BKMR models revealed the negative relation of eight OH-PAHs with FEV1, FVC or RTL; nine phthalate metabolites may counteract an overall effect of eight OH-PAHs on FEV1, FVC or RTL. The findings indicated that urinary phthalate metabolites may counteract the negative association of urinary OH-PAHs on FEV1 or FVC, which may be partially linked to shorter RTL regarding biological aging.

5.
Horm Metab Res ; 51(11): 729-734, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31683343

RESUMO

Contrasting data about the association between proliferative diabetic retinopathy (PDR) and vitamin D status remain unknown. First, a hospital-based cross-sectional study consisting of 889 diabetic retinopathy (DR) and non-DR (NDR) patients was admitted. Further the accumulated evidence was performed to explore the association and dose-response relationship. Our study indicated that the odd ratio for PDR in vitamin D deficiency (VDD) individuals was significantly increased (1.60, 95% CI 1.06-2.42), compared with NDR in vitamin D sufficiency individuals, adjusted by age, sex, diabetic duration, and HbA1c. Four studies plus our study with data on vitamin D levels in 4970 patients with PDR and NDR subjects are compared. Association between vitamin D deficiency and risk of PDR exists (OR=1.69, 95% CI 1.40-2.05; I2=0%, p=0.61). Association between a nonlinear trend for vitamin D decrease with risk of DR was significant (chi2=16.53, p=0.0003). No significant heterogeneity in identified studies was found (goodness of fit chi2=2.98, p=0.225). It is concluded that vitamin D deficiency is significantly associated with risk of proliferative diabetic retinopathy.

6.
Comput Biol Med ; 115: 103524, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31698234

RESUMO

Causal graphs play an essential role in the determination of causalities and have been applied in many domains including biology and medicine. Traditional causal graph construction methods are usually data-driven and may not deliver the desired accuracy of a graph. Considering the vast number of publications with causality knowledge, extracting causal relations from the literature to help to establish causal graphs becomes possible. Current supervised-learning-based causality extraction methods requires sufficient labeled data to train a model, and rule-based causality extraction methods are limited by the predefined patterns. This paper proposes a causality extraction framework by integrating rule-based methods and unsupervised learning models to overcome these limitations. The proposed method consists of three modules, including data preprocessing, syntactic pattern matching, and causality determination. In data preprocessing, abstracts are crawled based on attribute names before sentences are extracted and simplified. In syntactic pattern matching, these simplified sentences are parsed to obtain the part-of-speech tags, and triples are achieved based on these tags by matching the two designed syntactic patterns. In causality determination, four verb seed sets are initialized, and word vectors are constructed for the verbs in both the seed sets and the triples by applying an unsupervised machine learning model. Causal relations are identified by comparing the similarity between the verbs in each triple and that in each seed set to overcome the limitation of the seed sets. Causality extraction results on the attributes from the risk factors for Alzheimer's disease show that our method outperforms Bui's method and Alashri's method in terms of precision, recall, specificity, accuracy and F-score, with increases in the F-score of 8.29% and 5.37%, respectively.

7.
Sci Total Environ ; 702: 135056, 2019 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-31731128

RESUMO

Limited researches are available on seasonal variation of inhalation exposure of polycyclic aromatic hydrocarbons (PAHs) and its cancer risk assessment in China. We recruited 20 fresh postgraduates and measured outdoor and indoor (dormitories, offices and laboratories) daily PM2.5 concentrations in four seasons (seven consecutive days in every season) during 2014 -2015, calculated daily potential doses of personal exposure to total Benzo[a]pyrene equivalent concentration (BaPeq) in the microenvironments based on the total BaPeq and the time-activity patterns, and estimated incremental lifetime cancer risk (ILCR) using Monte Carlo method. Daily average concentrations of PM2.5-bound ∑PAHs on the campus ranked from high to low were winter, autumn, spring, summer in the dormitories and offices. Daily average concentration of PM2.5-bound ∑PAHs were higher in indoor environments than outdoor in the same season, except for that of PM2.5-bound ∑PAHs in laboratories in the winter. Median values of ILCR in both sexes from high to low were winter (men vs. women: 5.35e-9 vs. 4.96e-9), spring (3.71e-9 vs. 4.00e-9), autumn (2.92e-9 vs. 3.02e-9), summer (1.71e-9 vs. 1.87e-9). Indoor and outdoor PM2.5-bound PAHs concentrations showed seasonal and spatial variations. The ILCR value for PM2.5-bound PAHs was higher in women than in men.

8.
Eur J Med Chem ; : 111851, 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31761381

RESUMO

Forty-eight analogues of CP-31398, an antitumor agent modulated the mutant p53 gene were synthesized and their cytotoxicities against four cancer cell lines with different p-53 status including bladder cell T24 (w-p53), gastric cell MGC-803 (m-p53), prostate cell DU145 (m-p53), prostate cell PC-3 (null-p53), lung cell A549 (w-p53) and normal liver cell line HL-7702 (w-p53) were examined. (E)-2-(4-Nitrostyryl)-4-(3-dimethylaminopropyl)-aminoquinazoline (10ah) was identified as the most potent compound in anti-proliferation against MGC-803 cells, with IC50 lowed to 1.73 µM, far potency than that of CP-31398. Molecular mechanism study revealed that 10ah and CP-31398 differ greatly in mechanism to exert their antitumor properties. 10ah could intercalate into DNA and resulted in significant DNA double-strand break. 10ah-treatment in MGC-803 cells increased the expression of p53, phosphorylated p53 (p-p53), CDK4, p21 to cause cell cycle arrest at G2/M phase, significantly up-regulated the levels of pro-apoptosis proteins Bak, Bax, Bim while down-regulated the anti-apoptosis proteins Bcl-2, Bcl-xL and the levels of cyclin B1, fluctuated the intracellular reactive oxygen species (ROS), Ca2+ and mitochondrial membrane potential, activated Caspase-9 and Caspase-3 to induce apoptosis. 10ah also displayed potent anticancer efficiency against MGC-803 xenograft tumors models, with tumor growth inhibition (TGI) up to 61.8% at 20 mg/kg without obvious toxicity.

9.
BMC Neurol ; 19(1): 272, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690277

RESUMO

BACKGROUD: Patients with acute ischemic stroke (AIS) often experience low serum free triiodothyronine (FT3), but the association of low FT3 with stroke severity, subtype and prognosis has not yet been thoroughly studied, and the molecular events underlying these clinical observation were also unclear. METHODS: We retrospectively collected 221 cases of AIS and 182 non-AIS cases with detailed clinical data from our department. FT3 concentrations were measured on admission to predict functional outcome within 3 months using multivariable models adjusted for other risk factors. Receiver operating characteristic (ROC) curves were calculated to define the best cutoff value of FT3 of stroke severity, subtypes and neurological outcome. Gene set enrichment, pathway mapping and network analyses of deferentially expressed genes (DEGs) were performed. RESULTS: FT3 was significantly decreased in AIS patients with National Institutes of Health Stroke Scale (NIHSS) > 3 and 3-months modified Rankin Scale (mRS) > 2. The cut-off value of FT3 for NIHSS on admission was 4.30 pmol/L. Also, FT3 level was significantly lower in large artery atherosclerosis (LAA) group and cardioembolism (CE) group than that in small vessel occlusion (SVO). FT3 value served as an independent predictor for neurological outcomes for which the cut-off value of FT3 was 4.38 pmol/l. Gene ontology (GO) analysis showed that the biological function of DEGs was mainly enriched in multicellur organism, neuron differentiation and cellular response to hypoxia. The cellular components were involved in extracelluar region, exosome and matrix, and the molecular functions were transcriptional activator activity, DNA binding and nuclear hormone receptor binding. Signal pathways analysis was indicative of neuroactive ligand-receptor interaction, thyroid hormone signaling pathway, and protein digestion and absorption these DEGs were involved in. Six related gene were identified as hubs from the protein-protein interaction (PPI) networks. Three modules were selected from PPI, of which MMP4, ADRA2C and EIF3E were recognized as the seed genes. CONCLUSIONS: Low FT3 value on admission was associated with stroke severity, subtype and prognosis. In addition, DEGs identified from bioinformatics analysis are likely to be candidates for elucidating clinical outcomes with low FT3, and provide us with therapeutic targets for improving stroke prognosis.

10.
Ir J Med Sci ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31691888

RESUMO

BACKGROUND: To explore the value of the right hemi-diaphragmatic excursion (DE) and its variation in predicting extubation outcome in mechanically ventilated patients with COPD. METHODS: All included patients with COPD received mechanical ventilation (MV) and were ready to wean from MV. After patients passed the 30 min spontaneous breathing trail (SBT), extubation was considered to be feasible, and the right DE measured by ultrasound at 0 min, 5 min, and 30 min of SBT were named as DE0, DE5, and DE30, respectively. RESULTS: Twenty-five patients succeeded extubation; 12 patients failed. The area under receiver operator characteristic curve (AUCROC) of DE30 and ΔDE30-5 (the variation between 30 and 5 min) were 0.762 and 0.835; a cutoff value of DE30 > 1.72 cm and ΔDE30-5 > 0.16 cm were associated with a successful extubation with a sensitivity of 76% and 84%, a specificity of 75% and 83.3%, respectively. The predictive probability equation of the DE30 plus ∆DE30-5 was P = 1/[1 + e-(-5.625+17.689×∆DE30-5+1.802×DE30)], a cutoff value of P > 0.626 was associated with a successful extubation with the AUCROC of 0.867, a sensitivity of 92%, and a specificity of 83.3%. CONCLUSION: The combination of DE30 and ∆DE30-5 could improve the predictive value and could be used as the predictor of extubation outcome in mechanically ventilated patients with COPD.

11.
Balkan Med J ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674172

RESUMO

Background: Myocardial impairment is a major complication of sepsis and is an important prognostic predictor for septic patients. Therefore, early accurate diagnosis and timely management of septic cardiomyopathy is critical to achieve favorable outcomes. Aims: This study aimed to investigate the epidemiology and independent risk factors of septic cardiomyopathy. Study Design: Septic patients were divided into two groups: non-cardiomyopathy group (n = 45) and septic cardiomyopathy group (n = 48). Methods: Ninety-three septic patients in the intensive care unit (ICU) were recruited for this prospective study performed between May 2016 and June 2018. All patients received standardized treatments. Blood samples were collected and transthoracic echocardiography was performed within 24 hours of ICU admission. Septic patients with one ultrasound abnormality but no history of heart disease were diagnosed as having septic cardiomyopathy. Plasma histones, troponin (cTnI), and NT-proBNP were determined using ELISA. Sequential Organ Failure Assessment (SOFA) scores were evaluated, and vasopressor use and outcomes of ICU stay were analyzed. Spearman rank analysis was used to determine the correlation between plasma histone H4 and other parameters. Binary logistic regression and ROC curve analysis were used to determine the risk factors for septic cardiomyopathy. Results: Compared with the non-cardiomyopathy group, the septic cardiomyopathy group had significantly elevated plasma H4 and cTnI levels, a higher SOFA score, more frequent vasopressor use, and a higher mortality rate (P < 0.05). Plasma histone H4 levels were positively correlated with cTnI (r = 0.577, P = 0.000), NT-proBNP (r = 0.349, P = 0.001), and SOFA scores (r = 0.469, P = 0.000). Binary logistic regression and ROC curve analyses revealed that elevated plasma histone H4 levels and vasopressor use were important risk factors for septic cardiomyopathy (P < 0.05). Conclusion: Our study suggests that elevated plasma histone H4 levels could be used to predict septic cardiomyopathy in patients with sepsis.

12.
Biosci Rep ; 39(11)2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31682263

RESUMO

Catestatin (CTS), a catecholamine-release inhibitory peptide, exerts pleiotropic cardiac protective effects. Pulmonary embolism caused by deep vein thrombosis involving vascular dysfunction. The present study aims to investigate the effects of CTS on thrombus formation that may inhibit the development of pulmonary embolism and its potential pathway. Acute pulmonary embolism (APE) model was developed as an in vivo model. The effects of CTS on mice with APE were examined. Human pulmonary artery endothelial cells (HPAECs) were pretreated with CTS before thrombin stimulation, and endothelial inflammation and underlying mechanisms were evaluated in vitro. That plasma CTS level was decreased in APE mice, while the number of platelets was significantly increased. The decreased circulating CTS level negatively associated with the number of platelets. CTS administration increased the survival rate of APE mice and protected against microvascular thrombosis in lung. APE-induced the increase in platelets number and plasma von Willebrand factor (VWF) were inhibited by CTS. Platelets from CTS-treated APE mice showed impaired agonist-induced platelets aggregation and spreading. CTS also ameliorated APE-induced the systemic inflammatory response. In in vivo study, thrombin-induced the increase in inflammation, TLR-4 expression and p38 phosphorylation were abrogated by CTS in HPAECs. Furthermore, TLR-4 overexpression inhibited the effect of CTS on VWF release and inflammation in HPAECs. Collectively, CTS increases thrombus resolution by attenuating endothelial inflammation at partially via inhibiting TLR-4-p38 pathway. The present study may provide a novel approach for anti-thrombosis.

13.
Environ Pollut ; : 113509, 2019 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-31767236

RESUMO

Evidence is available about the associations of phthalates or their metabolites with blood lipids, however, the mixture effects of multiple phthalate metabolites on blood lipid traits remain largely unknown. In this pilot study, 106 individuals at three age groups of <18, 18- and ≥60 years were recruited from the residents (n = 1240) who were randomly selected from two communities in Wuhan city, China. The participants completed the questionnaire survey and physical examination as well as provided urine samples in the winter of 2014 and the summer of 2015. We measured urinary levels of nine phthalate metabolites using a high-performance liquid chromatography-tandem mass spectrometry. We estimated the associations of individual phthalate metabolite with blood lipid traits by linear mixed effect (LME) models, and assessed the overall association of the mixture of nine phthalate metabolites with blood lipid traits using Bayesian kernel machine regression (BKMR) models. LME models revealed the negative association of urinary mono-2-ethylhexyl phthalate (MEHP) with total cholesterol (TC) as well as of urinary mono-benzyl phthalate or urinary MEHP with low density lipoprotein cholesterol (LDL-C). BKMR models revealed the negative overall association of the mixture of nine phthalate metabolites with TC or LDL-C, and DEHP metabolites (especially MEHP) had a greater contribution to TC or LDL-C levels than non-DEHP metabolites. The findings indicated the negative overall association of the mixture of nine phthalate metabolites with TC or LDL-C. Among nine phthalate metabolites, MEHP was the most important component for the changes of TC or LDL-C levels, implying that phthalates exposure may disrupt lipid metabolism in the body.

14.
Microb Pathog ; 138: 103827, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682994

RESUMO

BACKGROUND: Several studies have suggested a role for the gut microbiome and cytokines in atherosclerosis development, but combined analyses of the changes of the gut microbiota and cytokines have not been explored previously. METHODS: We treated ApoE-/- and wild-type mice with a high-fat diet for 12 weeks. The gut microbiome and cytokine composition were analyzed using 16S ribosomal DNA sequencing and RayBio Quantibody Arrays, respectively. GO and KEGG analysis were performed to rationalize the potential mechanisms involved in the process of atherosclerosis. RESULTS: Gut bacterial characteristics in ApoE-/- mice were clearly separated and 21 gut bacterial clades were detected by the LEfSe analysis showing significant differences during the development of atherosclerosis. The relative abundance of Verrucomicrobia, Bacteroidaceae, Bacteroides, and Akkermansia showed significant positive correlations with serum total cholesterol, triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Additionally, the relative abundance of Ruminococcaceae was positive with the level of HDL and the abundance of Rikenellaceae showed a negative relationship with the level of TG and LDL. Thirteen differentially expressed proteins were identified with P-value < 0.05. CXCL5, FGF2, and E-Selectin were significantly negatively associated with Akkermansia and Verrucomicrobia. Additionally, CXCL5 was significantly negatively correlated with Bacteroides and Bacteroidaceae. Three "cellular component" subcategories, 24 ″molecular function" subcategories, 752 ″biological process" subcategories and 29 statistically remarkable KEGG pathway categories were identified. CONCLUSIONS: Gut microbiota changes of the mice having atherosclerosis and their relationship with the inflammatory status could be one of the major etiological mechanisms underlying atherosclerosis.

15.
Hear Res ; 384: 107827, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31683075

RESUMO

The association between shift work and hearing loss is unclear. We aimed to evaluate this association in a Chinese population independently and in combination with occupational noise. A total of 11,196 participants of the Dongfeng-Tongji cohort study were included. Shift work was self-reported and hearing loss was defined as a pure-tone mean of 25 dB or higher at 0.5, 1, 2, and 4 kHz in any ear. The Robust Poisson method were used to assess the relationship between shift work and hearing loss, and the prevalence ratios (PRs) were calculated. Compared to individuals who reported no shift work, the PRs of bilateral hearing loss were significantly higher for a shift work duration of fewer than 10 years in women, (PR = 1.024, 95% confidence interval [CI] = 1.002-1.053), but not in men (PR = 1.016, 95% confidence interval [CI] = 0.998-1.035). The association between short duration of shift work and bilateral hearing loss was just statistically significant in women when those with occupational noise exposure were excluded (PR = 1.067, 95%CI = 1.015-1.122). When shift work and occupational noise exposure were combined, the PRs for hearing loss were highest among individuals with the longest shift work (≥10 years) and longest noise exposure (≥20 years) durations, whether for bilateral (PR = 1.114, 95%CI = 1.068-1.162) or any ear (PR = 1.065, 95%CI = 1.034-1.096). A short duration of shift work may be a risk factor for hearing loss in women and could increase the prevalence of hearing loss when combined with occupational noise.

16.
Plant J ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31713923

RESUMO

The centromere, as an essential element to mediate chromosome segregation, is epigenetically determined by CENH3-containing nucleosomes as a functional marker; therefore the accurate deposition of CENH3 is crucial to chromosome transmission. We characterized the deposition of CENH3 in maize by over-expression and mutational analysis. Our results revealed that over-expressing CENH3 in callus is lethal while over-expressing GFP-CENH3 and CENH3-YFP in callus and plants is not and can be partly deposited normally. Different mutations of GFP-CENH3 demonstrated that CENH3-Thr4 in the N terminus was needed for the deposition as a positive phosphorylation site and the last five amino acids in the C terminus are necessary for deposition. The C terminal tail of CENH3 is confirmed to be responsible for the interaction of CENH3 and histone H4, which indicates that CENH3 maintains deposition in centromeres via interacting with H4 to form stable nucleosomes. For GFP-CENH3 and CENH3-YFP, the fused tags at the termini probably affect the structure of CENH3 and reduce its interaction with other proteins, which in turn could decrease proper deposition. Taken together, multiple amino acids or motifs were shown to play essential roles in CENH3 deposition, which is suggested to be affected by numerous factors in maize.

17.
Med Hypotheses ; 132: 109233, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31606702

RESUMO

The guidelines for cardiopulmonary resuscitation (CPR) in pediatric advanced life support suggest that midazolam is the preferred agent for sedation in patients with mild hypothermia, whereas children with cardiac arrest (CA) are at a crucial stage regarding their immature nervous system. Studies have shown that midazolam may have a detrimental effect on the developmental of the pediatric nervous system. Our previous study found that midazolam induced neuronal damage after CPR in young rats. It is speculated that: midazolam causes the potential injury of neurons by inhibiting mitochondrial autophagy expression and is an important factor for the poor prognosis in children after successful CPR. This project intends to adopt the modified asphyxiant CPR model in juvenile rats. Survival rate, neurological function and histopathological changes were evaluated to determine the protective effects of appropriate sedation depth on cerebral ischemia-reperfusion injury in juvenile rats after CPR. Combined with cell biology and molecular biology related technologies, the mechanism by which the mitochondrial pinkl-parkin signaling pathway induces autophagy to inhibit neuronal apoptosis may be key factor in the protective effects of sedation depth on the brain. The aim of this study is to provide experimental evidence and elucidate the mechanisms of improvement of cerebral ischemia-reperfusion injury by sedation depth in children after successful CPR and to lay a theoretical and experimental basis for clinical treatment.

18.
Int J Oncol ; 55(6): 1249-1260, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31638165

RESUMO

The purpose of the present study was to compare metabolites from formalin­fixed and paraffin­embedded (FFPE) pancreatic tissue blocks with those identified in optimal cutting temperature (OCT)­embedded pancreatic tissue blocks. Thus, ultra­performance liquid chromatograph­mass spectrometry/mass spectrometry­based metabolic profiling was performed in paired frozen (n=13) and FFPE (n=13) human pancreatic adenocarcinoma tissue samples, in addition to their benign counterparts. A total of 206 metabolites were identified in both OCT­embedded and FFPE tissue samples. The method feasibility was confirmed through reproducibility and a consistency assessment. Partial least­squares discriminant analysis and heatmap analysis reliably distinguished tumor and normal tissue phenotypes. The expression of 10 compounds, including N­acetylaspartate and creatinine, was significantly different in both OCT­embedded and FFPE tumor samples. These ten compounds may be viable candidate biomarkers of malignant pancreatic tissues. The super­categories to which they belonged exhibited no significant differences between FFPE and OCT­embedded samples. Furthermore, purine, arginine and proline, and pyrimidine metabolism used a shared pathway found in both OCT­embedded and FFPE tissue samples. These results supported the notion that metabolomic data acquired from FFPE pancreatic cancer specimens are reliable for use in retrospective and clinical studies.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31647417

RESUMO

It has been recently shown that deep learning models such as convolutional neural networks (CNN), deep belief networks (DBN) and recurrent neural networks (RNN), exhibited remarkable ability in modeling and representing fMRI data for the understanding of functional activities and networks because of their superior data representation capability and wide availability of effective deep learning tools. For example, spatial and/or temporal patterns of functional brain activities embedded in fMRI data can be effectively characterized and modeled by a variety of CNN/DBN/RNN deep learning models as shown in recent studies. However, it has been rarely investigated whether it is possible to directly infer hierarchical brain networks from volumetric fMRI data using deep learning models such as DBN. The perceived difficulties of such studies include very large number of input variables, very large number of training parameters, the lack of effective software tools, the challenge of results interpretation, and etc. To bridge these technical gaps, we designed a novel volumetric sparse deep belief network (VS-DBN) model and implemented it through the popular TensorFlow open source platform to reconstruct hierarchical brain networks from volumetric fMRI data based on the Human Connectome Project (HCP) 900 subjects release. Our experimental results showed that a large number of interpretable and meaningful brain networks can be robustly reconstructed from HCP 900 subjects in a hierarchical fashion, and importantly, these brain networks exhibit reasonably good consistency and correspondence across multiple HCP task-based fMRI datasets. Our work contributed a new general deep learning framework for inferring multiscale volumetric brain networks and offered novel insights into the hierarchical organization of functional brain architecture.

20.
J Diabetes Investig ; 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31661606

RESUMO

AIMS/INTRODUCTION: Elevated serum cancer antigen 19-9 (CA19-9) levels have been found in diabetes patients in most observational studies; however, whether there is a causal association between CA19-9 and diabetes mellitus is unclear. MATERIALS AND METHODS: Our study was carried out based on the Dongfeng-Tongji cohort comprising 27,009 individuals. We first investigated the associations between serum CA19-9 levels and incident diabetes mellitus risk in a prospective cohort study (12,700 individuals). Then, we explored the potential causal relationship between CA19-9 and diabetes mellitus risk in a cross-sectional study (3,349 diabetes mellitus patients and 8,341 controls) using Mendelian randomization analysis. A weighted genetic risk score was calculated by adding the CA19-9 increasing alleles in five single-nucleotide polymorphisms (rs17271883, rs3760776 and rs3760775 in FUT6, rs11880333 in CA11, rs265548 in B3GNT3, and rs1047781 in FUT2), which were identified in a previous genome-wide association study on serum CA19-9 levels. RESULTS: In the prospective study, a total of 1,004 incident diabetes mellitus patients were diagnosed during a mean 4.54-year follow-up period. Elevated serum CA19-9 level was associated with a higher incident diabetes risk after adjustment for confounders, with a hazard ratio of 1.20 (95% confidence interval 1.11-1.30) per standard deviation (12.17 U/mL) CA19-9 increase. Using the genetic score to estimate the unconfounded effect, we did not find a causal association of CA19-9 with diabetes risk (odds ratio per weighted CA19-9-increasing allele: 0.99, 95% confidence interval 0.94-1.04; P = 0.61). CONCLUSIONS: The present study did not support a causal association of serum CA19-9 with diabetes risk. CA19-9 might be a potential biomarker of incident diabetes mellitus risk.

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