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1.
Ann Hepatol ; : 100672, 2022 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-35065261

RESUMO

INTRODUCTION: Among all immune cells, natural killer (NK) cells play an important role as the first line of defense against tumor. The purpose of our study is to observe whether the NK cell counts can predict the overall survival of patients with hepatocellular carcinoma (HCC). METHODS: To develop a novel model, from January 2010 to June 2015, HCC patients enrolled in hospital were divided into training and validation cohort. Cox multiple regression analysis was used to analyze the independent risk factors for 1-year, 3-year and 5-year overall survival (OS) of patients with HCC, and the nomogram was used to establish the prediction model. In addition, the decision tree was established to verify the contribution of NK cell counts to the survival of patients with HCC. RESULTS: The model used in predicting overall survival of HCC included six variables (namely, NK cell counts, albumin (ALB) level, alpha-fetoprotein (AFP) level, portal vein tumor thrombus (PVTT), tumor number and treatment). The C-index of nomogram model in HCC patients predicting 1-year, 3-year and 5-year overall survival was 0.858, 0.788 and 0.782 respectively, which was higher than tumor-lymph node-metastasis (TNM) staging system, Okuda, model for end-stage liver disease (MELD), MELD-Na, the Chinese University Prognostic Index (CUPI) and Japan Integrated Staging (JIS) scores (p < 0.001). The decision tree showed the specific 5-year OS probability of HCC patients under different risk factors, and found that NK cell counts were the third in the column contribution. CONCLUSIONS: Our study emphasizes the utility of NK cell counts for exploring interactions between long-term survival of HCC patients and predictor variables.

2.
Eur Radiol ; 2022 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-35064804

RESUMO

OBJECTIVES: To quantitatively measure and compare the whole-brain iron deposition between attention-deficit/hyperactivity disorder (ADHD) patients and typically developing (TD) children using the quantitative susceptibility mapping (QSM) technique. METHODS: This study was approved by the institutional review board of our institution (No. [2019]328). Fifty-one patients between 6 and 14 years with clinical diagnosis of ADHD and 51 age- and gender-paired TD children were enrolled. For each participant, the 3D T1 and multi-echo GRE sequence were performed to acquire the whole-brain data with 3.0-T MRI. The QSM maps were calculated using STISuite toolbox. After normalizing the QSM images to MNI space, the voxel-based analysis was used to compare the iron content between the two groups. Pearson's correlation test was used to assess the associations between the iron content and the score of the tablet-PC-based cancellation test, which was done to evaluate the attention concentration level. RESULTS: Iron deficiency was observed in several brain regions in children with ADHD, including bilateral striatums, anterior cingulum, olfactory gyrus, and right lingual gyri. In further correlation analysis, the left anterior cingulum was found to show positive correlation with the symptom severity (r = 0.326, p < 0.05). CONCLUSIONS: Our study demonstrated that the iron deficiency in several brain regions might be related with ADHD, which might be valuable for further studies. And QSM might have the potential efficacy in the auxiliary diagnosis of ADHD. KEY POINTS: • Iron deficiency was observed in several brain regions in children with ADHD, which include bilateral striatums, the critical regions in the dopaminergic transmitter system. • The iron content in the left ACG may have association with the symptom severity of ADHD. • QSM might have the potential efficacy in the auxiliary diagnosis of ADHD.

3.
Virulence ; 13(1): 5-18, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34969351

RESUMO

Edwardsiella species in aquatic environments exist either as individual planktonic cells or in communal biofilms. These organisms encounter multiple stresses, include changes in salinity, pH, temperature, and nutrients. Pathogenic species such as E. piscicida, can multiply within the fish hosts. Additionally, Edwardsiella species (E. tarda), can carry antibiotic resistance genes (ARGs) on chromosomes and/or plasmids, that can be transmitted to the microbiome via horizontal gene transfer. E. tarda serves as a core in the aquatic resistome. Edwardsiela uses molecular switches (RpoS and EsrB) to control gene expression for survival in different environments. We speculate that free-living Edwardsiella can transition to host-living and vice versa, using similar molecular switches. Understanding such transitions can help us understand how other similar aquatic bacteria switch from free-living to become pathogens. This knowledge can be used to devise ways to slow down the spread of ARGs and prevent disease outbreaks in aquaculture and clinical settings.

4.
J Clin Transl Hepatol ; 9(5): 647-654, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34722179

RESUMO

Background and Aims: Spontaneous bacterial peritonitis (SBP) is one of the leading causes of death in patients with liver cirrhosis. We aimed to establish a prognostic model to evaluate the 1-year survival of cirrhosis patients after the first episode of SBP. Methods: A prognostic model was developed based on a retrospective derivation cohort of 309 cirrhosis patients with first-ever SBP and was validated in a separate validation cohort of 141 patients. We used Uno's concordance, calibration curve, and decision curve (DCA) analysis to evaluate the discrimination, calibration, and clinical net benefit of the model. Results: A total of 59 (19.1%) patients in the derivation cohort and 42 (29.8%) patients in the validation cohort died over the course of 1 year. A prognostic model in nomogram form was developed with predictors including age [hazard ratio (HR): 1.25; 95% confidence interval (CI): 0.92-1.71], total serum bilirubin (HR: 1.66; 95% CI: 1.28-2.14), serum sodium (HR: 0.94; 95% CI: 0.90-0.98), history of hypertension (HR: 2.52; 95% CI: 1.44-4.41) and hepatic encephalopathy (HR: 2.06; 95% CI: 1.13-3.73). The nomogram had a higher concordance (0.79) compared with the model end-stage liver disease (0.67) or Child-Turcotte-Pugh (0.71) score. The nomogram also showed acceptable calibration (calibration slope, 1.12; Bier score, 0.15±0.21) and optimal clinical net benefit in the validation cohort. Conclusions: This prediction model developed based on characteristics of first-ever SBP patients may benefit the prediction of patients' 1-year survival.

5.
Front Neurosci ; 15: 711528, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34759789

RESUMO

Objective: To investigate the profiles of brain volumetric measurements in children with attention deficit hyperactivity disorder (ADHD), and the consistency of these brain volumetric measurements derived from the synthetic and conventional T1 weighted MRI (SyMRI and cT1w MRI). Methods: Brain SyMRI and cT1w images were prospectively collected for 38 pediatric patients with ADHD and 38 healthy children (HC) with an age range of 6-14 years. The gray matter volume (GMV), white matter volume (WMV), cerebrospinal fluid (CSF), non-WM/GM/CSF (NoN), myelin, myelin fraction (MYF), brain parenchyma volume (BPV), and intracranial volume (ICV) were automatically estimated from SyMRI data, and the four matching measurements (GMV, WMV, BPV, ICV) were extracted from cT1w images. The group differences of brain volumetric measurements were performed, respectively, using analysis of covariance. Pearson correlation analysis and interclass correlation coefficient (ICC) were applied to evaluate the association between synthetic and cT1w MRI-derived measurements. Results: As for the brain volumetric measurements extracted from SyMRI, significantly decreased GMV, WMV, BPV, and increased NON volume (p < 0.05) were found in the ADHD group compared with HC; No group differences were found in ICV, CSF, myelin volume and MYF (p > 0.05). With regard to GMV, WMV, BPV, and ICV estimated from cT1w images, the group differences between ADHD and HC were consistent with the results estimated from SyMRI. And these four measurements showed noticeable correlation between the two approaches (r = 0.692, 0.643, 0.898, 0.789, respectively, p < 0.001; ICC values are 0.809, 0.782, 0.946, 0.873, respectively). Conclusion: Our study demonstrated a global brain development disability, but normal whole-brain myelination in children with ADHD. Moreover, our results demonstrated the high consistency of brain volumetric indices between synthetic and cT1w MRI in children, which indicates the high reliability of SyMRI in the child-brain volumetric analysis.

6.
Eur Radiol ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34642808

RESUMO

OBJECTIVE: To evaluate the ability of quantitative MRI parameters for predicting dysthyroid optic neuropathy (DON). METHODS: We retrospectively collected and analyzed the clinical features and 3.0 T MRI data of 59 patients with Graves orbitopathy (GO), with (n = 26) and without DON (n = 33). We compared MRI quantitative parameters, including the modified muscle index (mMI), proptosis, volume of intra-orbital fat, mean apparent diffusion coefficient value, and T2 value of the optic nerve among patients with and without DON. A logistic regression analysis was performed to identify the risk factors associated with DON. Moreover, we performed a receiver operating characteristic curve analysis and decision curve analysis to evaluate the diagnostic performance of the identified parameters for DON. RESULTS: We studied 118 orbits (43 and 75 with and without DON, respectively). The mMI and mean T2 value of the optic nerve were significantly greater in orbits with DON (p < 0.001). A greater mMI at 21 mm (odds ratio (OR), 1.039; 95% confidence interval (CI): 1.019, 1.058) and higher mean T2 value of the optic nerve (OR, 1.035; 95% CI: 1.017, 1.054) were associated with a higher risk of DON. A model combining the mMI at 21 mm and mean T2 values for the optic nerve effectively predicted DON in patients with GO, with a sensitivity and specificity of 95.3% and 76%, respectively. CONCLUSION: A quantitative MRI parameter combining the mMI at 21 mm and mean T2 value of the optic nerve can be an effective imaging marker for identifying DON. KEY POINTS: • Patients with GO and DON had greater mMI than those without DON. • Optic nerves in patients with DON demonstrated an increased T2 value. • The quantitative MRI parameter combining the mMI at 21 mm and mean T2 value of the optic nerve is the most effective method for diagnosing DON.

7.
Transl Psychiatry ; 11(1): 526, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645783

RESUMO

Brain function relies on efficient communications between distinct brain systems. The pathology of major depressive disorder (MDD) damages functional brain networks, resulting in cognitive impairment. Here, we reviewed the associations between brain functional connectome changes and MDD pathogenesis. We also highlighted the utility of brain functional connectome for differentiating MDD from other similar psychiatric disorders, predicting recurrence and suicide attempts in MDD, and evaluating treatment responses. Converging evidence has now linked aberrant brain functional network organization in MDD to the dysregulation of neurotransmitter signaling and neuroplasticity, providing insights into the neurobiological mechanisms of the disease and antidepressant efficacy. Widespread connectome dysfunctions in MDD patients include multiple, large-scale brain networks as well as local disturbances in brain circuits associated with negative and positive valence systems and cognitive functions. Although the clinical utility of the brain functional connectome remains to be realized, recent findings provide further promise that research in this area may lead to improved diagnosis, treatments, and clinical outcomes of MDD.


Assuntos
Conectoma , Transtorno Depressivo Maior , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Rede Nervosa/diagnóstico por imagem
8.
J Hepatocell Carcinoma ; 8: 1253-1267, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34708007

RESUMO

Background and Aims: Although antiviral treatment has been shown to reduce mortality in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients with high HBV-DNA levels, it is still unclear whether it is useful in reducing mortality in patients with low HBV-DNA levels. Methods: A retrospective analysis of 756 HBV-associated HCC patients at the Beijing Ditan Hospital with HBV-DNA levels < 500 IU/mL was conducted between January 2008 and June 2017. Patients were divided into antiviral and non-antiviral groups based on whether they received nucleos(t)ide analogue (NA) treatment when they were diagnosed with HCC in our hospital for the first time. We used 1:4 frequency matching by age, gender, tumor size, Barcelona Clinic Liver Cancer (BCLC) staging, anti-tumor therapy, cirrhosis, diabetes, and hyperlipoidemia to compare the antiviral (n = 366) and non-antiviral (n = 100) groups. A Cox multivariate regression analysis was employed to evaluate the effects of NA therapy on the hazard ratio (HR), and the Kaplan-Meier survival curve was used to determine the mortality risk in patients with HCC. A Log rank test was performed to analyze the effects of NA therapy on the survival rate of patients with HCC. Results: After propensity score matching, the 1-, 3-, and 5-year overall survival (OS) rates for the antiviral and non-antiviral groups were 82.5%, 68.6%, and 52.2%, and 61.0%, 51.0%, and 38.0%, respectively. The l-year progression-free survival (PFS) rates for the two groups were 68.0% and 47.0%, respectively. The OS of the antiviral group was significantly higher than that of the control group (P < 0.001, P = 0.001, and P = 0.013, respectively). The 1-year PFS for the antiviral group was also significantly better than that for the non-antiviral groups (P = 0.005). After adjusting for confounding prognostic factors in the Cox model, the HR of 5-year death after antiviral treatment was 0.721 (95% confidence interval [CI], 0.530-0.980, P = 0.037). Antiviral therapy is an independent protective factor for 5-year mortality in patients with HCC and low-level viremia. Conclusion: Antiviral therapy significantly reduced mortality in HCC patients with low HBV-DNA levels.

9.
ESC Heart Fail ; 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34713619

RESUMO

AIMS: To distinguish between constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM) using cardiac magnetic resonance feature tracking (CMR-FT) left ventricle (LV) diastolic time-strain curve patterns and myocardial strain. METHODS AND RESULTS: A total of 32 CP patients, 27 RCM patients, and 25 control subjects were examined by CMR-FT and analysed for global strain, segmental strain, and LV time-strain curve patterns in the longitudinal, circumferential, and radial directions. Speckle tracking echocardiography (STE) strain imaging was performed in some cases. The peak global longitudinal strain (GLS) and global circumferential strain (GCS) of the RCM group were lower than those of the CP group. GLS [median (interquartile range) CP vs. RCM: -11.15 (-12.85, -9.35) vs. -6.5 (-8.75, -4.85), P < 0.001] and GCS (CP vs. RCM: -16.89 ± 5.11 vs. -13.37 ± 5.79, P < 0.001). In circumferential and radial directions, the strain ratios of the LV lateral/septal wall (LW/SW) of the CP group were significantly lower than those of the RCM group at the basal and mid segments. The CS ratio of LW/SW at the basal segment [CP vs. RCM: 0.95 (0.85, 1.25) vs. 1.43 (1.18, 1.89), P < 0.001] and mid segment [CP vs. RCM: 1.05 (0.92, 1.15) vs. 1.18 (1.06, 1.49), P = 0.026]. The RS ratio of LW/SW at the basal segment [CP vs. RCM: 0.97 (0.76, 1.37) vs. 1.55 (1.08, 2.31), P = 0.006] and mid segment [CP vs. RCM: 0.95 (0.70, 1.28) vs. 1.79 (1.32, 2.92), P < 0.001]. In the longitudinal and circumferential directions, the characteristic 'plateau' pattern of time-strain curves could be seen in the CP but not in the RCM during the diastole. The GCS ratio of 0-50%/50-75% diastolic period of the CP was higher than that of the RCM [CP vs. RCM: 17.01 (8.67, 23.75) vs. 5.38 (1.93, 11.24), P = 0.001], while the GCS ratio of 50-75%/75-100% diastolic period was lower than that of the RCM [CP vs. RCM: 0.36 (0.15, 1.67) vs. 1.12 (0.70, 5.58), P < 0.001]. The peak GLS (sensitivity, 85%; specificity, 78%) and the GCS ratio of 0-50%/50-75% diastolic period (sensitivity, 88%; specificity, 73%) had higher differential diagnosis value. CONCLUSIONS: The CMR-FT could distinctly differentiate CP from RCM based on LV myocardial strain and LV time-strain curve patterns. The characteristic 'plateau' pattern of the time-strain curve is specific for CP and not RCM and this curve can also be duplicated by STE.

10.
Brain Imaging Behav ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491528

RESUMO

To investigate the quantitative profiles of brain grey matter (GM) in pediatric drug-naïve ADHD patients using synthetic magnetic resonance imaging (SyMRI). A total of 37 drug-naïve pediatric ADHD and 27 age- and gender-matched healthy controls (HC) were enrolled in this study. Each subject underwent both SyMRI and conventional 3D T1-FSPGR scans. Quantitative parameters, T1 and T2 maps, were extracted from the SyMRI data. Between-group quantitative maps were compared using a general linear model analysis. Pearson correlation analysis was conducted to assess the association between significantly altered MR indices and clinical measurements in ADHD. Compared with the HC group, altered T1 and T2 relaxometry times in the ADHD group were mainly distributed in GM regions of the cerebellum, attention and execution control network, default mode network, and limbic areas. Moreover, the T1 value of the right cerebellum 8 was negatively correlated with the attention concentration level in ADHD (R = 0.140, P = 0.0225). With regards to T2 map, the associations were observed between the attention level of ADHD patients and left fusiform gyrus (R = 0.251, P = 0.0016), and right cerebellum crus2 (R = 0.142, P = 0.0214). Altered T1, T2 values found in specific regions of GM, including cerebellum, attention and execution control network, default mode network, and limbic areas, may reveal widespread micromorphology changes, i.e., brain iron deficiency, low myelin content, and enlarged vascular interstitial space in ADHD patients. Thus, T1, T2 values might be promising imaging markers for future ADHD studies.

11.
Phytomedicine ; 91: 153722, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34488188

RESUMO

BACKGROUND: Yangyin Fuzheng Jiedu Prescription (YFJP), a formulated Chinese herbal medicine, has been used for several decades in the treatment of hepatocellular carcinoma (HCC). Previous studies have demonstrated its anti-tumor efficacy, but the mechanism of action remains uncharacterized. This study aims to evaluate the therapeutic effect of YFJP on H22 tumor-bearing mice. PURPOSE: This study aimed to evaluate the therapeutic effect of YFJP on H22 tumor-bearing mice. METHODS: A total of 50 male H22 tumor-bearing mice were randomly divided into 6 groups and continuous administered either different doses of YFJP or cyclophosphamide (CTX) or normal saline. for 2 weeks. The tumor appearance was observed by taking photos, and the tumor volume, weight, spleen and thymus index were calculated. Morphology of tumor infiltrating lymphocytes and the CD8+ T lymphocytes were detected through HE staining immunohistochemistry respectively. The frequency of CD3+, CD8+ T cell subsets and co-inhibitory receptors PD-1, TIGIT, Tim-3 on CD8+ T cell in spleen, peripheral blood and tumor tissue was performed by flow cytometry. Meanwhile, the killing and apoptotic functions of CD8+ T cells in tumor tissues were also detected by the same method. The levels of cytokines in peripheral blood were detected by Milliplex map mouse highs sensitivity T Cell kit. The expression of T cell transcription factor T-bet and Eomes in tumor tissues were observed by Western blot. RESULTS: We found that YFJP could effectively inhibit the solid tumor growth and spleen indexes, but showed little effect on the body weight in the established mouse model of HCC. Furthermore, we investigated the effect of YFJP on the phenotypic and functional changes of T cells. The results showed that YFJP could maintain the high ratio of CD3+ and CD8+ T cells in the peripheral blood, spleen, and tumor tissues while decreasing the expression of programmed cell death-1 (PD-1), T cell immunoglobulin and ITIM domain (TIGIT), T cell immunoglobulin domain and mucin domain-3 (Tim-3) in CD8+ T cells, respectively. Surprisingly, PD-1/Tim-3 double-positive T cells in the peripheral blood and tumor tissues were significantly decreased. Additionally, YFJP restored the cytotoxicity of tumor-infiltrating T cells and delayed their apoptosis in H22 tumor-bearing mice. In addition, treatment with YFJP significantly decreased the expression of inflammatory and immunosuppressive cytokines (including IL-1ß, IL-6, and IL-10) in the serum and tumor tissues whereas enhancing that of effector cytokines TNF-α, and IFN-γ. Moreover, T cell transcription factors T-bet increased and Eomes degraded in the tumor tissues upon YFJP treatment. CONCLUSION: In conclusion, these results demonstrated that YFJP could simultaneously exert anti-tumor immune response in H22 tumor-bearing mice by alleviating T cell exhaustion and immunosuppression.


Assuntos
Linfócitos T CD8-Positivos , Carcinoma Hepatocelular , Medicamentos de Ervas Chinesas , Neoplasias Hepáticas , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Citocinas , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Masculino , Camundongos
12.
Biology (Basel) ; 10(9)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34571793

RESUMO

Mercury (Hg) is a global pollutant that may potentially have serious impacts on human health and ecologies. The gaseous elemental mercury (GEM) exchanges between terrestrial surfaces and the atmosphere play important roles in the global Hg cycle. This study investigated GEM exchange fluxes over two land cover types (including Artemisia anethifolia coverage and removal and bare soil) using a dynamic flux chamber attached to the LumexR RA915+ Hg analyzer during the growing season from May to September of 2018, in which the interactive effects of plant coverage and meteorological conditions were highlighted. The daily mean ambient levels of GEM and the total mercury concentrations of the soil (TSM) were determined to be 12.4 ± 3.6 to 16.4 ± 5.6 ng·m-3 and 32.8 to 36.2 ng·g-1, respectively, for all the measurements from May to September. The GEM exchange fluxes (ng·m-2·h-1) during the five-month period for the three treatments included the net emissions from the soil to the atmosphere (mean 5.4 to 7.1; range of -27.0 to 47.3), which varied diurnally, with releases occurring during the daytime hours and depositions occurring during the nighttime hours. Significant differences were observed in the fluxes between the vegetation coverage and removal during the growing months (p < 0.05). In addition, it was determined that the Hg fluxes were positively correlated with the solar radiation and air/soil temperature levels and negatively correlated with the air relative humidity and soil moisture under all the conditions (p < 0.05). Overall, the results obtained in this study demonstrated that the grassland soil served as both a source and a sink for atmospheric Hg, depending on the season and meteorological factors. Furthermore, the plants played an important inhibiting role in the Hg exchanges between the soil and the atmosphere.

13.
Oncoimmunology ; 10(1): 1942673, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249476

RESUMO

The prognosis of hepatocellular carcinoma (HCC) is extremely poor, of which hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) accounts for the majority in China. Immune checkpoint inhibitors have become an effective immunotherapy method for the treatment of HCC, but they are mainly used for T cells. NK cells play a vital role as the first line of defense against tumors. Therefore, we explored the characteristic expression pattern of immune checkpoints on NK cells of HBV-HCC patients. We analyzed the correlation between the co-expression of TIGIT and TIM-3 and the clinical progress of patients with HBV-HCC. The co-expression of TIGIT and TIM-3 on NK cells is elevated in patients with HBV-HCC. TIGIT+TIM-3+NK cells showed exhausted phenotypic characteristics and displayed dysfunction manifested as weakened killing function, reduced cytokine production, and proliferation function. TIGIT+TIM-3+NK cells participate in NK cells function exhaustion and are closely related to the disease progression of patients with HBV-HCC, suggesting a new target for future immunotherapy.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , China , Progressão da Doença , Receptor Celular 2 do Vírus da Hepatite A/genética , Vírus da Hepatite B/genética , Humanos , Células Matadoras Naturais , Receptores Imunológicos
14.
Nat Plants ; 7(8): 1015-1025, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34282286

RESUMO

Inferring the intrinsic and extrinsic drivers of species diversification and phenotypic disparity across the tree of life is a major challenge in evolutionary biology. In green plants, polyploidy (or whole-genome duplication, WGD) is known to play a major role in microevolution and speciation, but the extent to which WGD has shaped macroevolutionary patterns of diversification and phenotypic innovation across plant phylogeny remains an open question. Here, we examine the relationship of various facets of genomic evolution-including gene and genome duplication, genome size, and chromosome number-with macroevolutionary patterns of phenotypic innovation, species diversification, and climatic occupancy in gymnosperms. We show that genomic changes, such as WGD and genome-size shifts, underlie the origins of most major extant gymnosperm clades, and notably, our results support an ancestral WGD in the gymnosperm lineage. Spikes of gene duplication typically coincide with major spikes of phenotypic innovation, while increased rates of phenotypic evolution are typically found at nodes with high gene-tree conflict, representing historic population-level dynamics during speciation. Most shifts in gymnosperm diversification since the rise of angiosperms are decoupled from putative WGDs and instead are associated with increased rates of climatic occupancy evolution, particularly in cooler and/or more arid climatic conditions, suggesting that ecological opportunity, especially in the later Cenozoic, and environmental heterogeneity have driven a resurgence of gymnosperm diversification. Our study provides critical insight on the processes underlying diversification and phenotypic evolution in gymnosperms, with important broader implications for the major drivers of both micro- and macroevolution in plants.


Assuntos
Cycadopsida/genética , Evolução Molecular , Variação Genética , Genoma de Planta , Filogenia , Poliploidia , Fenótipo
15.
Eur J Radiol ; 141: 109815, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34130234

RESUMO

PURPOSE: To explore radiological changes of the lacrimal gland (LG) in Graves' ophthalmopathy (GO) based on multi-parametric quantitative MRI and its clinical utility in LG diagnosis and activity in GO. METHODS: We enrolled 99 consecutive patients with GO (198 eyes) and 12 Graves' Disease (GD) patients (24 eyes) from July 2018 to June 2020. Clinical, laboratory, and MRI data were collected at the first visit. Based on clinical activity scores, eyes with GO were subdivided into active and inactive groups. T2-relaxation time (T2) and the absolute reduction in T1-relaxation time (ΔT1) were determined. After MRI and processing, we performed descriptive data analysis and group comparisons. Novel logistic regression predictive models were developed for diagnosing and staging GO. Diagnostic performance of MRI parameters and models was assessed by receiver operating characteristic curve analysis. RESULTS: LG in GO group had significantly higher T2 and ΔT1 values than the GD group [106.25(95.30,120.21) vs. 83.35(78.15,91.45), P<0.001, and 662.62(539.33,810.95) vs. 547.35(458.62,585.57), P = 0.002, respectively]. The GO group had higher T2 of LG indicating higher disease activity [110.93(102.54,127.67) vs. 93.29(87.06,101.96), P < 0.001]. Combining T2 and ΔT1 values of LG, Model I had higher diagnostic value for distinguishing GO from GD (AUC=0.94, 95 %CI: 0.89,0.99, P<0.001). Meanwhile, T2 of LG had higher diagnostic value for grading GO activity (AUC = 0.84, 95 %CI: 0.76,0.92, P<0.001). CONCLUSIONS: Multi-parametric quantitative MRI parameters of the LG in GO were significantly altered. Novel models combining LG T2 and ΔT1 values showed excellent predictive performances in diagnosing GO. Furthermore, T2 of LG showed practical utility for staging GO.


Assuntos
Oftalmopatia de Graves , Aparelho Lacrimal , Oftalmopatia de Graves/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética
16.
Front Oncol ; 11: 645162, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33996562

RESUMO

Comparing MRI and histopathology, this study aims to comprehensively explore the potential application of 18F-trifluoromethylated D-cysteine (S-[18F]CF3-D-CYS) in evaluating glioma by using orthotopic C6 glioma models. Sprague-Dawley (SD) rats (n = 9) were implanted with C6 glioma cells. Tumor growth was monitored every week by multiparameter MRI [including dynamic contrast-enhanced MRI (DCE-MRI)], [18F]FDG, S-[18F]CF3-D-CYS, and [18F]FDOPA PET imaging. Repeated scans of the same rat with the two or three [18F]-labeled radiotracers were investigated. Initial regions of interest were manually delineated on T2WI and set on the same level of PET images, and tumor-to-normal brain uptake ratios (TNRs) were calculated to semiquantitatively assess the tracer accumulation in the tumor. The tumor volume in PET and histopathology was calculated. HE and Ki67 immunohistochemical staining were further performed. The correlations between the uptake of S-[18F]CF3-D-CYS and Ki67 were analyzed. Dynamic S-[18F]CF3-D-CYS PET imaging showed tumor uptake rapidly reached a peak, maintained plateau during 10-30 min after injection, then decreased slowly. Compared with [18F]FDG and [18F]FDOPA PET imaging, S-[18F]CF3-D-CYS PET demonstrated the highest TNRs (P < 0.05). There were no significant differences in the tumor volume measured on S-[18F]CF3-D-CYS PET or HE specimen. Furthermore, our results showed that the uptake of S-[18F]CF3-D-CYS was significantly positively correlated with tumor Ki67, and the poor accumulated S-[18F]CF3-D-CYS was consistent with tumor hemorrhage. There was no significant correlation between the S-[18F]CF3-D-CYS uptakes and the Ktrans values derived from DCE-MRI. In comparison with MRI and histopathology, S-[18F]CF3-D-CYS PET performs well in the diagnosis and evaluation of glioma. S-[18F]CF3-D-CYS PET may serve as a valuable tool in the clinical management of gliomas.

17.
Artigo em Inglês | MEDLINE | ID: mdl-34055016

RESUMO

Introductionand Aim. Patients with cirrhosis are often hospitalized repeatedly for a variety of complications. This retrospective study aimed to assess the effects of minimal hepatic encephalopathy (MHE) and Biejia-Ruangan (BR) on first hospital readmission in nonalcoholic cirrhosis patients without previous overt hepatic encephalopathy (OHE) or hepatocellular carcinoma (HCC). Materials and Methods. A total of 176 hospitalized patients with nonalcoholic cirrhosis were included in this retrospective study. Patients who were first admitted to Beijing Ditan Hospital of Capital Medical University from January 2017 to September 2019 were enrolled. The primary endpoint was their first liver-related hospital readmission. The risk factors for readmission were analyzed by Cox proportional hazard regression analysis. Results. A total of 176 nonalcoholic cirrhosis patients without previous OHE or HCC were included; 57 patients (32.4%) were diagnosed with MHE, and 63 patients (35.8%) were administered BR (2 g, three times a day). Multivariate analysis revealed that nonalcoholic cirrhosis patients with MHE (HR, 5.805; 95% CI, 3.007-11.206; x, P < 0.001) and a higher Model for End-Stage Liver Disease (MELD) score (HR, 1.145; 95% CI, 1.068-1.227; P < 0.001) had an increased risk of first hospital readmission, and patients treated with BR (HR, 0.318; 95% CI, 0.151-0.670; P=0.003) had a decreased risk of first hospital readmission. Conclusion. MHE increased the risk of hospital readmission in nonalcoholic cirrhosis patients without previous OHE or HCC, and this risk was decreased by BR administration.

18.
ACS Appl Mater Interfaces ; 13(18): 21379-21389, 2021 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-33914506

RESUMO

The rational design of continuous covalent organic framework (COF)-based membranes is challenging for desalination applications, mainly due to the larger intrinsic pore size of COFs and defects in the crystalline film, which lead to a negligible NaCl rejection ratio. In this work, we first demonstrated a COF-based desalination membrane with in situ cross-linking of a COF-TpPa layer by trimesoyl chloride (TMC) to stitch the defects between COF crystals and cross-link the COF cavity with high-cross-linking degree networks to enhance NaCl rejection. With the addition of TMC monomers, both small spherical nodules and some elongated "leaf-like" features were observed on the membrane surface due to the appearance of nanovoids during cross-linking. The resulting COF-based desalination membrane had a water permeability of approximately 0.81 L m-2 h-1 bar-1 and offered substantial enhancement of the NaCl rejection ratio from being negligible to 93.3% at 5 bar. Mechanistic analysis indicated that the amidation reaction of the secondary amine in keto COF with TMC induced the formation of a highly porous network structure both in the cavity and on the exterior of COF, thereby successfully forming a continuous and nanovoid-containing selective layer for desalination. In addition, the membrane exhibited excellent desalting performance for real industrial wastewater with both low and high salinity. This study proposed that the introduction of a cross-linker to react with the terminal amine group and secondary amine in the backbone of the keto form of COF or its derivatives could provide a facile and scalable approach to fabricate a COF-based membrane with superior NaCl rejection. This opens a new fabrication route for COF-based desalination membranes, as well as extended applications in water desalination.

19.
BMC Cancer ; 21(1): 246, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33685417

RESUMO

BACKGROUND: Alpha-fetoprotein-negative hepatocellular carcinoma (AFP-NHCC) (< 8.78 ng/mL) have special clinicopathologic characteristics and prognosis. The aim of this study was to apply a new method to establish and validate a new model for predicting the prognosis of patients with AFP-NHCC. METHODS: A total of 410 AFP-negative patients with clinical diagnosed with HCC following non-surgical therapy as a primary cohort; 148 patients with AFP-NHCC following non-surgical therapy as an independent validation cohort. In primary cohort, independent factors for overall survival (OS) by LASSO Cox regression were all contained into the nomogram1; by Forward Stepwise Cox regression were all contained into the nomogram2. Nomograms performance and discriminative power were assessed with concordance index (C-index) values, area under curve (AUC), Calibration curve and decision curve analyses (DCA). The results were validated in the validation cohort. RESULTS: The C-index of nomogram1was 0.708 (95%CI: 0.673-0.743), which was superior to nomogram2 (0.706) and traditional modes (0.606-0.629). The AUC of nomogram1 was 0.736 (95%CI: 0.690-0.778). In the validation cohort, the nomogram1 still gave good discrimination (C-index: 0.752, 95%CI: 0.691-0.813; AUC: 0.784, 95%CI: 0.709-0.847). The calibration curve for probability of OS showed good homogeneity between prediction by nomogram1 and actual observation. DCA demonstrated that nomogram1 was clinically useful. Moreover, patients were divided into three distinct risk groups for OS by the nomogram1: low-risk group, middle-risk group and high-risk group, respectively. CONCLUSIONS: Novel nomogram based on LASSO Cox regression presents more accurate and useful prognostic prediction for patients with AFP-NHCC following non-surgical therapy. This model could help patients with AFP-NHCC following non-surgical therapy facilitate a personalized prognostic evaluation.


Assuntos
Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Nomogramas , alfa-Fetoproteínas/análise , Biópsia , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/terapia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Fígado/diagnóstico por imagem , Fígado/patologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
20.
Environ Int ; 153: 106524, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33773143

RESUMO

BACKGROUND AND OBJECTIVE: The growing impact of the COVID-19 pandemic has heightened the urgency of identifying individuals most at risk of infection. Per- and poly-fluoroalkyl substances (PFASs) are manufactured fluorinated chemicals widely used in many industrial and household products. The objective of this case-control study was to assess the association between PFASs exposure and COVID-19 susceptibility and to elucidate the metabolic dysregulation associated with PFASs exposure in COVID-19 patients. METHODS: Total 160 subjects (80 COVID-19 patients and 80 symptom-free controls) were recruited from Shanxi and Shandong provinces, two regions heavily polluted by PFASs in China. Twelve common PFASs were quantified in both urine and serum. Urine metabolome profiling was performed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). RESULTS: In unadjusted models, the risk of COVID-19 infection was positively associated with urinary levels of perfluorooctanesulfonic acid (PFOS) (Odds ratio: 2.29 [95% CI: 1.52-3.22]), perfluorooctanoic acid (PFOA) (2.91, [1.95-4.83], and total PFASs (∑ (12) PFASs) (3.31, [2.05-4.65]). After controlling for age, sex, body mass index (BMI), comorbidities, and urine albumin-to-creatinine ratio (UACR), the associations remained statistically significant (Adjusted odds ratio of 1.94 [95% CI: 1.39-2.96] for PFOS, 2.73 [1.71-4.55] for PFOA, and 2.82 [1.97-3.51] for ∑ (12) PFASs). Urine metabolome-PFASs association analysis revealed that 59% of PFASs-associated urinary endogenous metabolites in COVID-19 patients were identified to be produced or largely regulated by mitochondrial function. In addition, the increase of PFASs exposure was associated with the accumulation of key metabolites in kynurenine metabolism, which are involved in immune responses (Combined ß coefficient of 0.60 [95% CI: 0.25-0.95, P = 0.001]). Moreover, alternations in PFASs-associated metabolites in mitochondrial and kynurenine metabolism were also correlated with clinical lab biomarkers for mitochondrial function (serum growth/differentiation factor-15) and immune activity (lymphocyte percentage), respectively. CONCLUSION: Elevated exposure to PFASs was independently associated with an increased risk of COVID-19 infection. PFASs-associated metabolites were implicated in mitochondrial function and immune activity. Larger studies are needed to confirm our findings and further understand the underlying mechanisms of PFASs exposure in the pathogenesis of SARS-CoV2 infection.


Assuntos
Ácidos Alcanossulfônicos , COVID-19 , Poluentes Ambientais , Fluorcarbonetos , Ácidos Alcanossulfônicos/toxicidade , Caprilatos/toxicidade , Estudos de Casos e Controles , China/epidemiologia , Cromatografia Líquida , Poluentes Ambientais/toxicidade , Fluorcarbonetos/análise , Fluorcarbonetos/toxicidade , Humanos , Pandemias , RNA Viral , SARS-CoV-2 , Espectrometria de Massas em Tandem
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