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1.
Magn Reson Med Sci ; 2021 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-33642470

RESUMO

PURPOSE: To explore the feasibility of susceptibility-weighted imaging (SWI) for evaluating renal iron overload. METHODS: Twenty-eight rabbits were randomly assigned into control (n = 14) and iron (n = 14) group. In the 0th week, the study group was injected with iron dextran. Both groups underwent SWI examination at the 0th, 8th, and 12th week. The signal intensity (SI) of cortex and medulla was assessed. Angle radian value (ARV) calculated with phase image was taken as the quantitative value for cortical and medullary iron deposition. After the 12th week, the left kidneys of rabbits were removed for pathology. The difference in the ARV among three groups was analyzed using Kruskal-Wallis test. The difference of the iron content between two groups was analyzed through independent sample t-test. RESULTS: In the iron group: at the 12th week, eight rabbits were found to have decreased SI of only cortex, and the other six rabbits had decreased SI of cortex and medulla by the same degree; the ARV of cortex at the 8th and 12th week was significantly higher than that of the 0th week (P < 0.05); the ARV of the six rabbits' medulla at the 12th week was significantly higher than that of the 0th week, 8th week, and the other eight rabbits at the 12th week (P < 0.05); at the 12th week, eight rabbits (iron group) were found to have many irons only deposit in the cortex, and the others were found to have many irons deposit in both cortex and medulla; the iron content of cortex and six rabbits' medulla in the iron group was significantly higher than that of the control (P < 0.05). CONCLUSION: The ARV of SWI can be used to quantitatively assess the excess iron deposition in the kidneys. Excessive iron deposition mainly occurs in the cortex or medulla and causes their SWI SI to decrease.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33556028

RESUMO

This paper proposes a two-way multi-ringed forest (TMR-Forest) to estimating the malignancy of the pulmonary nodules for false positive reduction (FPR). Based on our previous work of deep decision framework, named MR-Forest, we generate a growing path mode on predefined pseudo-timeline of L time slots to build pseudo-spatiotemporal features. It synchronously works with FPR based on MR-Forest to help predict the labels from a dynamic perspective. Concretely, Mask R-CNN is first used to recommend the bounding boxes of ROIs and classify their pathological features. Afterward, hierarchical attribute matching is introduced to obtain the input ROIs' attribute layouts and select the candidates for their growing path generation. The selected ROIs can replace the fixed-sized ROIs' fitting results at different time slots for data augmentation. A two-stage counterfactual path elimination is used to screen out the input paths of the cascade forest. Finally, a simple label selection strategy is executed to output the predicted label to point out the input nodule's malignancy. On 1034 scans of the merged dataset, the framework can report more accurate malignancy labels to achieve a better CPM score of 0.912, which exceeds those of MR-Forest and 3DDCNNs about 2.8% and 4.7%, respectively.

3.
Ann Palliat Med ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33440975

RESUMO

BACKGROUND: To explore whole-liver histogram analysis (HA) with blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) in evaluating and diagnosing hepatic fibrosis (HF) in a CCl4-induced rabbit model. METHODS: One hundred rabbits were classified as CCl4-induced HF groups (n=80) and control group (n=20), and were scheduled for BOLD-fMRI examination on a 3.0T scanner. Whole-liver HA metrics, including the mean, median, skewness, kurtosis, inhomogeneity, entropy, and nth percentiles, were extracted from the R2* map. Parameters were compared among the different HF stages using receivers operating characteristic analysis and Mann-Whitney U-test. RESULTS: In all, 17, 18, 19, 17, and 15 rabbits were pathologically diagnosed as F0, F1, F2, F3, and F4, respectively. HA parameters, including the median, inhomogeneity, entropy, and the 75th and 90th percentiles of the BOLD R2* map, demonstrated significant positive correlations with the fibrosis stage (r=0.226-0.718, P≤0.039). The 75th percentiles demonstrated higher diagnostic efficacy than the other HA parameters in fibrosis staging, with an AUC value of 0.86 for ≥ F1, 0.87 for ≥ F2, 0.87 for ≥ F3, and 0.86 for ≥ F4. CONCLUSIONS: BOLD-fMRI HA provides increased diagnostic performance in staging HF, especially for the 75th percentiles.

4.
BMC Musculoskelet Disord ; 22(1): 60, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33430847

RESUMO

BACKGROUND: Displaced patellar fractures are commonly treated with open reduction and fixation with several different types of tension-band (TB) constructs. The main objective of this study was to compare the prevalence of postoperative complications after surgical stabilization of comminuted patellar fractures with either a modified Kirschner-wire tension band (MKTB), a cannulated-screw tension band (CSTB), or a ring-pin tension band (RPTB). METHODS: We conducted a retrospective and consecutive cohort study of comminuted patellar fractures (n = 334) stabilized using a TB construct. Postoperative premature loss of reduction, infection, and skin breakdown were compared according to the type of TB constructs received (MKTB, CSTB, or RPTB). The rate of implant removal due to symptomatic hardware was also evaluated. RESULTS: Fixation failure rate was significantly different among the groups (P = 0.013), with failure rates of 4.7% observed in the MKTB group,14.5% in the CSTB group, and 4.9% in the RPTB group. Skin breakdown and infection were not significantly different among the groups (Ps > 0.05). Due to symptomatic hardware, 40.5% of the patients in the MKTB group, 22.9% in the CSTB group, and 24.3% in the RPTB group underwent implant removal (P = 0.004). After adjusting for age, gender, comorbidities, number of supplementary screws/K-wires, and use of cerclage cables, multivariate regression analysis revealed that CSTB contributed to a 2.08-times greater risk of fixation failure compared to RPTB, while MKTB and RPTB were similar in risk of failure. In addition, it was found that patients who underwent MKTB fixation were more than twice as likely to undergo implant removal for symptomatic hardware compared with RPTB (odds ratio = 2.11, 95% CI = 1.20 to 3.72; P = 0.010). CONCLUSIONS: RPTB have advantage over MKTB and CSTB fixation in terms of symptomatic hardware and premature failure, respectively. LEVEL OF EVIDENCE: Therapeutic Level III.

5.
Reprod Domest Anim ; 2021 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-33492695

RESUMO

The microenvironment in the seminiferous tubules of buffalo changes with age, which affects the self-renewal and growth of spermatogonial stem cells (SSCs) and the process of spermatogenesis, but the mechanism remains to be elucidated. RNA-seq was performed to compare the transcript profiles of pre-pubertal buffalo (PUB) and adult buffalo (ADU) seminiferous tubules. In total, 17299 genes from PUB and ADU seminiferous tubules identified through RNA-seq, among which 12271 were expressed in PUB and ADU seminiferous tubules, 4027 were expressed in only ADU seminiferous tubules, and 956 were expressed in only PUB seminiferous tubules. Of the 17299 genes, we identified 13714 genes that had significant differences in expression levels between PUB and ADU through GO enrichment analysis. Among these genes, 5342 were significantly upregulated and possibly related to the formation or identity of the surface antigen on SSCs during self-renewal; 7832 genes were significantly downregulated, indicating that genes in PUB seminiferous tubules do not participate in the biological processes of sperm differentiation or formation in this phase compared with those in ADU seminiferous tubules. Subsequently, through the combination with KEGG analysis, we detected enrichment in a number of genes related to the development of spermatogonial stem cells, providing a reference for study of the development mechanism of buffalo spermatogonial stem cells in the future. In conclusion, our data provide detailed information on the mRNA transcriptomes in PUB and ADU seminiferous tubules, revealing the crucial factors involved in maintaining the microenvironment and providing a reference for further in vitro cultivation of SSCs.

6.
Hum Vaccin Immunother ; : 1-9, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33499718

RESUMO

In June 2019, the Advisory Committee on Immunization Practices (ACIP) changed the recommendation for routine 13-valent pneumococcal conjugate vaccine (PCV13) use in immunocompetent adults aged ≥65 years, including those with select chronic medical conditions (CMC). ACIP now recommends PCV13 for this group of adults based on shared clinical decision-making. Because adults with CMC continue to be at increased risk for pneumococcal disease, we assessed the cost-effectiveness of administering PCV13 in series with the recommended 23-valent pneumococcal polysaccharide vaccine (PPSV23) for adults aged ≥19 years with CMC. We used a probabilistic model following a cohort of 19-year-old adults. We used Monte Carlo simulation to estimate the impact on program, medical, and non-medical costs (in 2017 U.S. dollars [$], societal perspective), and pneumococcal disease burden when administering PCV13 in series with PPSV23. We used PCV13 efficacy and post-licensure vaccine effectiveness (VE) data to estimate VE against PCV13 type disease (separately for disease by serotype 3 [ST3], the most common PCV13 type, and all other PCV13 serotypes). We considered a range of estimates for sensitivity analyses. Analyses were performed in 2019. In the base case, assuming no PCV13 effectiveness against ST3 disease, adding a dose of PCV13 upon CMC diagnosis cost $689,299 per QALY gained. This declined to $79,416 per QALY if VE against ST3 was estimated to be equivalent to other PCV13-types. Administering PCV13 in series with the recommended PPSV23 for adults with CMC was not cost saving. Results were sensitive to estimated PCV13 VE against ST3 disease.

7.
Transbound Emerg Dis ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33417745

RESUMO

Infectious hematopoietic necrosis virus (IHNV) is a major fish viral pathogen causing acute clinical disease and death in a variety of salmonids. IHNV isolates have been classified into five major genogroups according to the phylogenetic analysis of partial G gene fragments or the complete G gene sequence: U, M, E, L and J. Genogroup U strains have been reported in North America and Japan prior to 1982, and genogroup J is the only genogroup that has been reported in China. Here, one of IHNV strain (BjLL) was isolated from a local farm in China and were characterized in this study. The homogenate tissues of infected fry induced IHNV-positive cytopathic effects in epithelioma papulosum cyprinid (EPC) cells that were confirmed by RT-PCR and sequencing. The complete genome sequence of BjLL comprised 11,129 nucleotides, which had been submitted to GenBank (accession no. MF509592). By the sequence comparison and phylogenetic analysis for the G gene sequence of BjLL with 51 reference sequences in GenBank, we confirmed that this Chinese isolate belonged to genogroup U. Furthermore, virus exposure experiments with juvenile rainbow trout were conducted to assess the virulence and pathogenicity of BjLL. Compared with GS-2014 of genogroup J, BjLL was an obviously less virulent strain that could result in lower mortality. Besides, typical clinical symptoms and pathological damages could be seen in fish following infection of BjLL. The present study is the first report of genogroup U IHNV infection in China and will provide essential information for future studies on pathogenesis of IHNV BjLL and development of efficient control strategies.

8.
Anesthesiology ; 134(3): 381-394, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33439974

RESUMO

BACKGROUND: Delayed neurocognitive recovery after surgery is associated with poor outcome. Most surgeries require general anesthesia, of which sevoflurane and propofol are the most commonly used inhalational and intravenous anesthetics. The authors tested the primary hypothesis that patients with laparoscopic abdominal surgery under propofol-based anesthesia have a lower incidence of delayed neurocognitive recovery than patients under sevoflurane-based anesthesia. A second hypothesis is that there were blood biomarkers for predicting delayed neurocognitive recovery to occur. METHODS: A randomized, double-blind, parallel, controlled study was performed at four hospitals in China. Elderly patients (60 yr and older) undergoing laparoscopic abdominal surgery that was likely longer than 2 h were randomized to a propofol- or sevoflurane-based regimen to maintain general anesthesia. A minimum of 221 patients was planned for each group to detect a one-third decrease in delayed neurocognitive recovery incidence in propofol group compared with sevoflurane group. The primary outcome was delayed neurocognitive recovery incidence 5 to 7 days after surgery. RESULTS: A total of 544 patients were enrolled, with 272 patients in each group. Of these patients, 226 in the propofol group and 221 in the sevoflurane group completed the needed neuropsychological tests for diagnosing delayed neurocognitive recovery, and 46 (20.8%) in the sevoflurane group and 38 (16.8%) in the propofol group met the criteria for delayed neurocognitive recovery (odds ratio, 0.77; 95% CI, 0.48 to 1.24; P = 0.279). A high blood interleukin-6 concentration at 1 h after skin incision was associated with an increased likelihood of delayed neurocognitive recovery (odds ratio, 1.04; 95% CI, 1.01 to 1.07; P = 0.007). Adverse event incidences were similar in both groups. CONCLUSIONS: Anesthetic choice between propofol and sevoflurane did not appear to affect the incidence of delayed neurocognitive recovery 5 to 7 days after laparoscopic abdominal surgery. A high blood interleukin-6 concentration after surgical incision may be an independent risk factor for delayed neurocognitive recovery.

9.
J Ethnopharmacol ; 270: 113811, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33444717

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hypecoum erectum has been used extensively in folk medicine to treat inflammation, fever, and pain. However, few investigations have been carried out on the biological activities related to its traditional use. The chemical constituents of this plant along with their anti-inflammatory and analgesic effects have yet to be revealed. AIM OF THE STUDY: This study aimed to support the traditional use of H. erectum by first assessing its anti-inflammatory and analgesic effects and then investigating its chemical constituents to identify any anti-inflammatory and/or analgesic compounds. MATERIAL AND METHODS: The in vivo anti-inflammatory and analgesic activities of the MeOH extract (ME), total alkaloid (AL), and non-alkaloid (Non-AL) fractions of H. erectum at doses of 200, 100, and 50 mg/kg and four major constituents (20, 21, 22, and 27) at doses of 100 and 50 mg/kg delivered via intragastrical administration were evaluated using carrageenan-induced paw edema and acetic acid-stimulated writhing animal models. A phytochemical study of the bioactive (AL) fraction was conducted using various chromatographic techniques, and the structures of the obtained isoquinolines were identified by multiple spectroscopic analyses and quantum chemical computations. Moreover, the anti-inflammatory activities of all the isolates were assessed in vitro based on the suppression of lipopolysaccharide-activated inflammatory mediators (COX-2, IL-1ß, and TNF-α) in RAW 264.7 macrophage cells. RESULTS: At the dose of 200 mg/kg, the three fractions (ME, AL, and Non-AL) of H. erectum ameliorated the paw edema by carrageenan-stimulated and reduced the number of writhing by acetic acid-induced in mice compared to the model group, with the AL fraction showing the most potent effects. Subsequent phytochemical investigation of the AL fraction led to the isolation of six new isoquinoline alkaloids (1-6) as well as 23 known analogues (7-29). However, compared to common isoquinolines, compounds 1-4 possess an additional nitrogen atom, while compound 5 has two additional nitrogen atoms. These additional atoms enrich the diversity of natural isoquinoline alkaloids. Further pharmacological evaluation in vivo revealed that the four major constituents (20, 21, 22, and 27) significantly relieved paw edema at 100 mg/kg, while protopine (20) and oxyhydrastinin (27) remarkably decreased the number of writhing at 100 mg/kg. In addition, most of the isolates displayed anti-inflammatory effects, as indicated by the inhibition of inflammatory mediators (COX-2, IL-1ß, and/or TNF-α) in vitro at a treatment concentration of 5 µg/mL. trans-benzindenoazepines (13), protopine (20), and 1,3,6,6-tetramethyl-5,6,7,8-tetrahyboisoquiolin-8-one (25) showed comparable anti-inflammatory activity to dexamethasone by inhibiting the secretion of IL-1ß. CONCLUSIONS: This investigation validated the traditional use of H. erectum by assessing its anti-inflammatory and analgesic effects. Phytochemical investigation revealed the diversity and novelty of the natural isoquinoline alkaloids in H. erectum. Four major isoquinolines were identified as the bioactive constituents of H. erectum. The findings provide scientific justification to support the traditional application of H. erectum for treating inflammatory and pain disorders.

10.
Environ Sci Technol ; 55(1): 120-128, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33325230

RESUMO

Short-term exposure to fine particulate matter (PM2.5) pollution is linked to numerous adverse health effects. Pollution episodes, such as wildfires, can lead to substantial increases in PM2.5 levels. However, sparse regulatory measurements provide an incomplete understanding of pollution gradients. Here, we demonstrate an infrastructure that integrates community-based measurements from a network of low-cost PM2.5 sensors with rigorous calibration and a Gaussian process model to understand neighborhood-scale PM2.5 concentrations during three pollution episodes (July 4, 2018, fireworks; July 5 and 6, 2018, wildfire; Jan 3-7, 2019, persistent cold air pool, PCAP). The firework/wildfire events included 118 sensors in 84 locations, while the PCAP event included 218 sensors in 138 locations. The model results accurately predict reference measurements during the fireworks (n: 16, hourly root-mean-square error, RMSE, 12.3-21.5 µg/m3, n(normalized)RMSE: 14.9-24%), the wildfire (n: 46, RMSE: 2.6-4.0 µg/m3; nRMSE: 13.1-22.9%), and the PCAP (n: 96, RMSE: 4.9-5.7 µg/m3; nRMSE: 20.2-21.3%). They also revealed dramatic geospatial differences in PM2.5 concentrations that are not apparent when only considering government measurements or viewing the US Environmental Protection Agency's AirNow visualizations. Complementing the PM2.5 estimates and visualizations are highly resolved uncertainty maps. Together, these results illustrate the potential for low-cost sensor networks that combined with a data-fusion algorithm and appropriate calibration and training can dynamically and with improved accuracy estimate PM2.5 concentrations during pollution episodes. These highly resolved uncertainty estimates can provide a much-needed strategy to communicate uncertainty to end users.

11.
Magn Reson Med ; 85(1): 346-356, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32726485

RESUMO

PURPOSE: To explore the value of MRI texture analysis in evaluating the presence and severity of early renal ischemia-reperfusion injury (IRI). METHODS: Healthy New Zealand rabbits were used (IRI group, N = 54; control group, N = 8). Rabbits in the IRI group underwent left renal artery clamping for 60 minutes. Magnetic resonance imaging was performed before and at 1, 12, 24, and 48 hours after IRI. The relationship between MRI texture features and histopathology parameters was assessed using Pearson's correlation coefficients. The diagnostic performance of texture features in kidney differentiation at different time points was assessed by receiver operating characteristic curve analysis. RESULTS: T2 WI_S(3,-3)Inverse_Difference_Moment had the strongest correlation with brush border destruction, tubular epithelial edema, necrosis, and cast (r = 0.56, -0.58, 0.62, and 0.69, respectively; all P < .001). BOLD_S(4,-4)Correlation had the strongest correlation with interstitial inflammatory cell infiltration (r = 0.63, P < .001). SWI_S(4,4)Difference_Entropy had the strongest correlation with microvessel density (r = 0.61, P < .001). The areas under the curve for T2 WI_S(3,-3)Inverse_Difference_Moment, SWI_S(4,4)Difference_Entropy, and BOLD_S(4,-4)Correlation in kidney differentiation before IRI and that at 1 and 12 hours after reperfusion were 0.76, 0.72, and 0.70, respectively; the values before IRI and at 24 and 48 hours after reperfusion were 0.84, 0.81, and 0.69, respectively. The area under the curve for T2 WI_S(3,-3)Inverse_Difference_Moment in kidney differentiation at 1 and 12 hours after reperfusion and that at 24 and 48 hours after reperfusion was 0.66. CONCLUSION: Magnetic resonance imaging texture analysis can be used for evaluating the presence and severity of early renal IRI.

12.
J Exp Clin Cancer Res ; 39(1): 270, 2020 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-33267897

RESUMO

BACKGROUND: Emerging evidence suggests that epithelial mesenchymal transition (EMT) and epigenetic mechanisms promote metastasis. Histone deacetylases (HDACs) and noncoding RNAs (ncRNAs) are important epigenetic regulators. Here, we elucidated a novel role of histone deacetylase 2 (HDAC2) in regulating EMT and CRC metastasis via ncRNA. METHODS: The expression of HDACs in CRC was analyzed using the public databases and matched primary and metastatic tissues, and CRC cells with different metastatic potentials (DLD1, HCT116, SW480 and SW620). Microarray analysis was used to identify differential genes in parental and HDAC2 knockout CRC cells. EMT and histone modifications were determined using western blot and immunofluorescence. Migration ability was assessed by transwell assay, and metastasis was assessed in vivo using a tail vain injection. Gene expression and regulation was assessed by RT-PCR, chromatin immunoprecipitation and reporter assays. Protein interaction was assessed by immunoprecipitation. Specific siRNAs targeting H19, SP1 and MMP14 were used to validate their role in HDAC2 loss induced EMT and metastasis. RESULTS: Reduced HDAC2 expression was associated with poor prognosis in CRC patients and found in CRC metastasis. HDAC2 deletion or knockdown induced EMT and metastasis by upregulating the long noncoding RNA H19 (LncRNA H19). HDAC2 inhibited LncRNA H19 expression by histone H3K27 deacetylation in its promoter via binding with SP1. LncRNA H19 functioned as a miR-22-3P sponge to increase the expression of MMP14. HDAC2 loss strongly promoted CRC lung metastasis, which was suppressed LncRNA H19 knockdown. CONCLUSION: Our study supports HDAC2 as a CRC metastasis suppressor through the inhibition of EMT and the expression of H19 and MMP14.

13.
Sci Rep ; 10(1): 21540, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33298979

RESUMO

With the advantages of small samples and high accuracy, Grey Model (GM) still has two major problems need to be addressed, high input data requirements and large margin of error. Hence, this paper proposes an algorithm based on Populational Entropy Based Mind Evolutionary Algorithm-Error Back Propagation Training Artificial Neural Algorithm to modify GM residual tail, which will not only keep the advantages of GM, but also expand its scope of use to various non-linear and even multidimensional objects. Meanwhile, it can avoid defects of other algorithms, such as slow convergence and easy to fall into the local minimum. In small samples data experiments, judging from SSE, MAE, MSE, MAPE, MRE and other indicators, this new algorithm has significant advantage over GM, BP algorithm and combined genetic algorithm in terms of simulation accuracy and convergence speed.

14.
Ann Palliat Med ; 9(6): 4187-4193, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33302680

RESUMO

BACKGROUND: End-stage renal disease (ESRD) patients often have cognitive dysfunction. The abnormal changes in the brains of ESRD patients are difficult to detect with routine imaging examination. Cognitive performance scales are also not an ideal tool because assessments using these scales can be subjective and might be difficult to administer in some ESRD patients. Functional magnetic resonance has the advantages of non-radiation, multidirectional imaging, good repeatability. Using resting-state functional magnetic resonance imaging (rs-fMRI) and an amplitude of low-frequency fluctuation (ALFF) algorithm, this study characterized spontaneous brain activity and explored its relationship with cognitive function in ESRD patients. The aim of this study was to provide objective functional imaging evidence to reveal the pathophysiological mechanism of cognitive dysfunction in ESRD patients. METHODS: This study recruited 35 ESRD patients and 25 healthy controls (HC) who were matched to the ESRD group by age, sex, and years of education. All study subjects were examined by Montreal Cognitive Assessment (MoCA) and rs-fMRI. Data Processing & Analysis of Brain Imaging (DPABI) V4.3 software was used to preprocess the data to obtain ALFF maps. The ALFF value of the cingulate gyrus was compared between the ESRD and HC groups. Subsequently, the correlation between the ALFF value of the cingulate gyrus and the MoCA score was analyzed in ESRD patients. RESULTS: Compared with the HC group, the ESRD group had a significantly lower MoCA score (P<0.05). The ALFF values of the anterior and middle cingulate gyri were significantly lower in the ESRD patients (Gaussian random field (GRF) corrected, voxel-level significance: P<0.001, cluster-level significance: P<0.05). No increased ALFF was observed in any brain regions. The ALFF values of the bilateral anterior cingulate gyri were positively correlated with the MoCA scores (r=0.768, 0.625, GRF corrected, voxel-level significance: P<0.01, cluster-level significance: P<0.05). CONCLUSIONS: Patients with ESRD showed impaired spontaneous brain activity in the bilateral anterior and middle cingulate gyri, suggesting that ALFF of the anterior cingulate gyrus may be an imaging indicator of cognitive dysfunction in ESRD patients.

15.
Sci Total Environ ; : 143332, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33187713

RESUMO

Trait-based approaches have been widely used to explore the relationships between submerged macrophytes and their surrounding environments. However, the effects of functional traits on ecological functions of submerged macrophytes in eutrophic lakes are still not well understood. Here, 1745 individuals of eight dominant submerged macrophyte species in 19 Yangtze floodplain lakes were collected and classified as needle-leaf (Myriophyllum spicatum, Ceratophyllum demersum, Stuckenia pectinatus, Najas minor) or flat-leaf (Vallisneria natans, Hydrilla verticillata, Potamogeton wrightii, Potamogeton maackianus) types according to photosynthetic trait-based cluster analysis. The flat-leaf type submerged macrophytes possessed greater photosynthetic (e.g. higher Fv/Fm) and morphological traits (e.g. higher SLA), while the needle-leaf types held greater stoichiometric traits (e.g. higher plant N/P). Moreover, the RDA analysis indicated that water depth (distribution depth of submerged macrophytes) was the key factor influencing functional traits of flat-leaf types, while it was water quality (e.g. WTP and WChl a) for the needle-leaf types. Furthermore, the flat-leaf types showed better performance in improving underwater light conditions (e.g. SD, Kd, Zeu/WD and Red/Blue) and water quality (e.g. WChl a and TSM). Additionally, distribution depth (WD) of the flat-leaf types was shallower than the needle-leaf types in eutrophic shallow lakes along the middle-lower reaches of the Yangtze River. Our study highlights that functional traits of submerged macrophytes in eutrophic shallow lakes affect their ecological functions.

16.
Gastric Cancer ; 2020 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-33159601

RESUMO

BACKGROUND: Aberrant activation of Wnt/ß-catenin signaling by dysregulated post-translational protein modifications, especially ubiquitination is causally linked to cancer development and progression. Although Lys48-linked ubiquitination is known to regulate Wnt/ß-catenin signaling, it remains largely obscure how other types of ubiquitination, such as linear ubiquitination governs its signaling activity. METHODS: The expression and regulatory mechanism of linear ubiquitin chain assembly complex (LUBAC) on Wnt/ß-catenin signaling was examined by immunoprecipitation, western blot and immunohistochemical staining. The ubiquitination status of ß-catenin was detected by ubiquitination assay. The impacts of SHARPIN, a core component of LUBAC on malignant behaviors of gastric cancer cells were determined by various functional assays in vitro and in vivo. RESULTS: Unlike a canonical role in promoting linear ubiquitination, SHARPIN specifically interacts with ß-catenin to maintain its protein stability. Mechanistically, SHARPIN competes with the E3 ubiquitin ligase ß-Trcp1 for ß-catenin binding, thereby decreasing ß-catenin ubiquitination levels to abolish its proteasomal degradation. Importantly, SHARPIN is required for invasiveness and malignant growth of gastric cancer cells in vitro and in vivo, a function that is largely dependent on its binding partner ß-catenin. In line with these findings, elevated expression of SHARPIN in gastric cancer tissues is associated with disease malignancy and correlates with ß-catenin expression levels. CONCLUSIONS: Our findings reveal a novel molecular link connecting linear ubiquitination machinery and Wnt/ß-catenin signaling via SHARPIN-mediated stabilization of ß-catenin. Targeting the linear ubiquitination-independent function of SHARPIN could be exploited to inhibit the hyperactive ß-catenin signaling in a subset of human gastric cancers.

17.
J Cancer ; 11(24): 7312-7319, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33193895

RESUMO

Background: It has been reported that local anesthetics are toxic to various types of cells. Furthermore, several local anesthetics have been confirmed to exert demethylation effects and regulate the proliferation of human cancer cells. Our previous findings suggest that lidocaine may exert potential antitumor activity and enhance the sensitivity of cisplatin to hepatocellular carcinoma in vitro and in vivo. A recent study proved that lidocaine sensitizes breast cancer cells to cisplatin via upregulation of RASSF1A, a promotor of tumor suppressive gene (TSG) demethylation. We sought to determine whether amide-type local anesthetics (lidocaine, ropivacaine and bupivacaine) exert growth-inhibitory effects on human hepatoma cells and to determine whether amide-type local anesthetics sensitize human hepatoma cells to cisplatin-mediated cytotoxicity via upregulation of RASSF1A expression. Methods: Human hepatoma cell lines HepG2 and BEL-7402 were incubated with lidocaine, ropivacaine and bupivacaine. The viability of local anesthetic-treated cells with or without cisplatin was investigated. Further, we evaluated RASSF1A expression after treatment of HepG2 and BEL-7402 cells with three local anesthetics and determined the influence of RASSF1A expression on the toxicity of cisplatin to these cells. Results: The viability of HepG2 and BEL-7402 cells was significantly decreased by treatment with amide-type local anesthetics (lidocaine, ropivacaine and bupivacaine). In these cells, the combination treatment with cisplatin and local anesthetics exhibited a stronger reduction in viability. Lidocaine, ropivacaine and bupivacaine promoted a significant increase in RASSF1A expression and a decrease in RASSF1A methylation. The combined treatment with both local anesthetics and cisplatin resulted in a significantly lower level of HepG2 and BEL-7402 cell viability than that with singular local anesthetics or cisplatin treatment. Moreover, local anesthetics enhanced the cytotoxicity of cisplatin against HepG2 and BEL-7402 cells, accompanied by an increase in RASSF1A expression. Conclusions: These data indicated that amide-type local anesthetics (lidocaine, ropivacaine and bupivacaine) have growth-inhibitory and demethylation effects in human hepatoma cells. We also found that these amide local anesthetics may enhance the cytotoxicity of cisplatin in human hepatocellular carcinoma cells possibly via upregulation of RASSF1A expression and demethylation.

18.
Cerebrovasc Dis ; 49(6): 575-582, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33176296

RESUMO

BACKGROUND: In acute ischemic stroke, diffusion-weighted imaging (DWI) volume is an independent predictive factor of poor outcome and an exclusion criterion for thrombolytic treatment. A simplified diameters method (ABC/2, orthogonal diameter [OD], and the maximum diameter [MD]) was proposed to replace the conventional measuring method and overcome the tedious and time-consuming defects, but its accuracy remains to be determined. OBJECTIVE: The objective of this study is to clarify the reliability and reproducibility of the diameter-based estimations in the infarct volume in DWI (Vol-DWI) measured by automated software. METHODS: Data of 316 patients with acute ischemic stroke who underwent MRI within 72 h at Jinling Hospital were retrospectively reviewed. Subgroup analysis by the location (cortex, white matter and deep gray nuclei, and combined) and volume (<70 and >70 mL) of cerebral infarction was evaluated. Relationship and consistency between the diameters methods and Vol-DWI were determined using Spearman rank correlation, Wilcoxon signed-rank test, and Bland-Altman plots. The OD and MD thresholds indicating infarct size >15, 70, and 100 mL were determined by generating receiver-operating characteristic (ROC) curves. Interobserver reliability was established using intraclass correlation coefficient and Bland-Altman plot. RESULTS: There was a strong positive correlation between the diameters and the Vol-DWI (ABC/2: r = 0.992, OD: r = 0.984, MD: r = 0.970, p < 0.001). Infarct volumes measured using the ABC/2 formula were significantly lower than those measured with Vol-DWI (Wilcoxon signed-rank test, z = 6.476, p < 0.001). Bland-Altman plot showed that the agreement of the volume <70 mL group, and white matter and deep gray nuclei groups was better than that of the other subgroups. For infarct volumes >15, 70, and 100 mL, the cutoff value for the MD was identified at 5, 6.9, and 8.4 cm, and the OD was identified at 12.47, 26.4, and 36.4 cm2, respectively, with a sensitivity and specificity >90%. CONCLUSIONS: The MD method was the best for achieving a rapid and excellent interobserver reliability for estimating infarct volume. Both OD and MD methods can quickly screen patients suitable for recanalization treatment and predict poor prognosis through threshold evaluation.

19.
J Pak Med Assoc ; 70 [Special Issue](9): 98-104, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33177736

RESUMO

OBJECTIVE: This study aimed to find polymorphic loci associated with OPLL in Mongolian and Han population, the relationship of 9 polymorphic loci in Runx2 and IL-15RA with OPLL were identified in Mongolian and Han populations in Inner Mongolia. METHODS: Gene polymorphism of two candidate genes Runx2 and IL-15RA were detected by sequencing in 99 OPLL patients of Han population and 98 patients of Mongolian people. Controls included 102 healthy Han people and 104 healthy Mongolian people. The result of sequencing of patients were compared with control subjects to screen loci with significant difference. RESULTS: In Han population, results of genotyping showed rs1321075 and rs12333172 in Runx2 and rs2296139 in IL-15RA differed between patients and healthy people (P<0.05); Genotype of rs1321075 and rs16873379 and rs2296139 in IL-15RA have significant difference between patients and controls in Mongolian people (P<0.05); There was no significant difference found in genotype and frequency of other loci (P>0.05). CONCLUSIONS: Polymorphism of rs1321075 and rs2296139 in Runx2 and IL-15RA may be responsible for OPLL in Mongolian and Han population patients. rs12333172 was related to OPLL in Han population and rs16873379 was responsible for OPLL in Mongolian people in Inner Mongolia.

20.
Elife ; 92020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33135632

RESUMO

To better understand a role of eIF4E S209 in oncogenic translation, we generated EIF4ES209A/+ heterozygous knockin (4EKI) HCT 116 human colorectal cancer (CRC) cells. 4EKI had little impact on total eIF4E levels, cap binding or global translation, but markedly reduced HCT 116 cell growth in spheroids and mice, and CRC organoid growth. 4EKI strongly inhibited Myc and ATF4 translation, the integrated stress response (ISR)-dependent glutamine metabolic signature, AKT activation and proliferation in vivo. 4EKI inhibited polyposis in ApcMin/+ mice by suppressing Myc protein and AKT activation. Furthermore, p-eIF4E was highly elevated in CRC precursor lesions in mouse and human. p-eIF4E cooperated with mutant KRAS to promote Myc and ISR-dependent glutamine addiction in various CRC cell lines, characterized by increased cell death, transcriptomic heterogeneity and immune suppression upon deprivation. These findings demonstrate a critical role of eIF4E S209-dependent translation in Myc and stress-driven oncogenesis and as a potential therapeutic vulnerability.

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