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1.
Hepatology ; 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34662449

RESUMO

BACKGROUND & AIMS: Surrogate endpoints that predict complications are necessary for assessment and approval of NASH therapies. We assessed associations between histologic and noninvasive tests of fibrosis (NITs) with liver-related complications in patients with NASH cirrhosis. APPROACH & RESULTS: Patients with compensated cirrhosis due to NASH were enrolled in two placebo-controlled trials of simtuzumab and selonsertib. Liver fibrosis at baseline and week 48 (W48) was staged by NASH CRN and Ishak classifications and a machine learning (ML) approach, hepatic collagen and α-SMA expression were quantified by morphometry, liver stiffness (LS) was measured by transient elastography, and serum NITs (ELF, NAFLD Fibrosis Score [NFS], and FIB-4) were calculated. Cox regression determined associations between these parameters at baseline and their changes over time with adjudicated liver-related clinical events. Among 1135 patients, 709 (62%) had Ishak stage 6 fibrosis, and median ELF and LS were 10.66 and 21.1 kPa, respectively. During a median follow-up of 16.6 months, 71 (6.3%) had a liver-related event; associated baseline factors included Ishak stage 6 fibrosis, and higher hepatic collagen, α-SMA expression, ML-based fibrosis parameters, LS, ELF, NFS, and FIB-4. Cirrhosis regression observed in 16% (176/1135) between BL and W48 was associated with a lower risk of events vs non-regression (1.1% [2/176] vs 7.2% [69/957]; HR: 0.16; 95%CI 0.04,0.65 [p=0.0104]). Conversely, after adjustment for baseline values, increases in hepatic collagen, α-SMA, ML-based fibrosis parameters, NFS, and LS were associated with an increased risk of events. CONCLUSIONS: In patients with compensated cirrhosis due to NASH, regression of fibrosis is associated with a reduction in liver-related complications. These data support the utility of histologic fibrosis regression and NITs as clinical trial endpoints for NASH cirrhosis.

2.
Opt Express ; 29(17): 27871-27881, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34615193

RESUMO

We investigated the characteristics of chaos-modulated pulses amplified by a pulsed master oscillator power amplifier (MOPA) for application in a new chaos lidar system in this study. Compared with the loss modulation applied in a continuous-wave (CW) time-gating scheme, the pulsed MOPA scheme could generate chaos-modulated pulses with much higher peak power, resulting in an improved peak-to-standard deviation of sidelobe level (PSLstd) in correlation-based lidar detection. When the pulsed MOPA scheme was applied at a duty cycle of 0.1% and pulse repetition frequency of 20 kHz, which correspond to specifications compliant with eye safety regulations, it outperformed the CW time-gating scheme with respect to PSLstd by 15 dB. For the first time, we applied the chaos lidar system with the pulsed MOPA scheme to execute high-resolution, high-precision three-dimensional (3D) face profiling from a distance of 5 m. We also added the corresponding PSLstd value to each pixel in the point clouds to generate false-color images; thus, we obtained 3D images of a scene with multiple objects at a range of up to 20 m.

3.
Oncol Lett ; 22(5): 802, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34630709

RESUMO

Laryngeal squamous cell carcinoma (LSCC) is a highly invasive malignant tumor in the head and neck area. As an oncogene, long non-coding RNA (lncRNA) nuclear enriched abundant transcript 1 (NEAT1) promotes cell proliferation, migration and invasion several types of cancer. The present study aimed to reveal the effects of NEAT1 on the progression of LSCC. Reverse transcription-quantitative PCR (RT-qPCR) was used to detect relative mRNA expression levels of NEAT1, microRNA (miR)-204-5p and semaphorin (SEMA) 4B. Kaplan-Meier analysis was used to analyze overall survival times. RNA in-situ hybridization (ISH) exhibited the distribution of NEAT1 and miR-204-5p in tissues. RNA fluorescence ISH was used to analyze the distribution of NEAT1 and miR-204-5p in the cells. Western blot analysis was used to detect the expression level of target proteins. Cell viability was analyzed using a MTT assay, while flow cytometry was used to determine cell apoptosis. Wound healing and Transwell invasion assays were used to value cell migration and invasion, respectively. RNA immunoprecipitation assay, bioinformatics prediction and a dual luciferase reporter assay were used to analyze the target relationship. The RT-qPCR results showed that NEAT1 was highly expressed and miR-204-5p had decreased expression in LSCC tissues and cells compared with that in the normal tissue and the 16HBE-14o cell line, respectively. Knockdown of NEAT1 using small interfering (si) RNA and overexpressed miR-204-5p both effectively inhibited the proliferation, migration and invasion of LSCC cells. Besides, further experiments revealed that miR-204-5p was a target of NEAT1. At the same time, silenced miR-204-5p reversed the anti-tumor effects of si-NEAT1. In addition, SEMA4B was targeted by miR-204-5p in LSCC cells and upregulated SEMA4B weakened the antitumor effects of miR-204-5p in LSCC cells. NEAT1 regulated the expression of SEMA4B by targeting miR-204-5p in LSCC cells. Overall, NEAT1 promoted the proliferation and invasion of LSCC cells by regulating the miR-204-5p/SEMA4B axis.

4.
Asian J Surg ; 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34629273

RESUMO

BACKGROUND: Intravascular leiomyomatosis (IVL) is a rare disease, especially with intracardiac extension. Early diagnosis and treatment are essential for IVL with intracardiac involvement because it can result in significant morbidity and mortality. CASE REPORT: We present a case of IVL with intracardiac extension, which was treated with one-stage surgery by a multidisciplinary surgical team. The patient recovered adequately and had no recurrence for 12 months after surgery. CONCLUSION: A one-stage surgical approach can be used to remove an IVL completely and is a good treatment option when the patien's condition is favorable.

5.
Ultrason Sonochem ; 78: 105738, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34509958

RESUMO

This study primarily explored the internal mechanism underlying the ultrasonication-induced release of antioxidant peptides. An oxhide gelatin solution was treated ultrasonically (power = 200, 300, and 400 W), followed by enzymatic hydrolysis and structural and morphological analysis. The results showed that ultrasonication increased not only the degree of hydrolysis (DH) and protein recovery rate of the oxhide gelatin but also the ABTS radical scavenging, DPPH radical scavenging, ferrous chelating, and ferric reducing activities of its hydrolysate. The oxhide gelatin hydrolysate treated with 300-W ultrasonication had the maximum antioxidant activities. Ultrasonication inhibited hydrogen bond formation, reduced the crosslinking between collagen molecules, transformed part of the folded structure into a helical structure, and lowered the thermal stability of collagen molecules. The micromorphological analysis revealed that ultrasonication caused the gelatin surface to become loose and develop cracks, and as the power of the ultrasonication increased, the repetition interval distance (dÅ) also increased. Moreover, ultrasonication improved the solubilization, surface hydrophobicity, and interface characteristics and increased the content of basic and aromatic amino acids in the hydrolysate. In conclusion, ultrasonication modifies the protein structure, which increases the enzyme's accessibility to the peptide bonds and further enhances antioxidant peptide release. These findings provide new insights into the application of ultrasonication in the release of antioxidant peptides.

6.
Zhongguo Zhong Yao Za Zhi ; 46(17): 4581-4584, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34581065

RESUMO

Clinical trail report is a summary of the process and results of clinical trail, an important basis to support the effectiveness and safety evaluation of drug marketing and an important technical data required for drug registration. Safety analysis is the main part and the most common issue of clinical trial report. In this article, it is summarized and analyzed the common problems found in the safety analysis part of the clinical trial report of new drugs of traditional Chinese medicine(TCM) in combination with the clinical professional evaluation of the application for marketing license of innovative TCM. The common problems in writing the safety aspects of clinical trail reports were summarized and analyzed, including the omissions of adverse events and laboratory test results, the failure to provide a detailed list of laboratory test outliers, the lack of professional depth in the analysis of the causal relationship between adverse events and TCM. In view of the common problems, it is suggested that the drug use degree, adverse events and adverse reactions, as well as laboratory examination should be considered. Check the three dimensions for necessary medical analysis, collation and summary and continuously improve the quality of safety analysis in clinical trial reports.


Assuntos
Ensaios Clínicos como Assunto , Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/efeitos adversos
7.
Phys Chem Chem Phys ; 23(36): 20489-20495, 2021 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-34499059

RESUMO

As there is a rising interest in upgrading cellulose to high-performance bio-products, the studies on innovative reaction media and processes have been leaping forward. Green solvents in terms of cellulose dissolution and brief processes for upgrading are critical to green chemistry. However, most solvent systems generally exhibit defects in harsh pH operating windows with limited temperature ranges, environmental pollution, long reaction times, complicated processes, etc. In this work, we have provided a novel molten salt hydrate (CaCl2·6H2O-LiCl) as a green solvent and investigated the role of hydrated molten salts in the dissolution process via the solid state nuclear magnetic resonance (NMR) technique. The cellulose could be dissolved in CaCl2·6H2O-LiCl molten salt hydrated at 120 °C with 3.0% solubility and regenerated in-situ by cooling down to ambient temperature. The regenerated cellulose exhibited a high solubility and excellent stability. From 7Li single pulse NMR experiments, it was observed that two types of Li+ existed in the cellulose dissolution, and the Li+ significantly impacted the dissolving process and the dissolution ability of cellulose. This work would provide an environmental-friendly strategy to prepare cellulose solutions for biocompatible cellulose materials.

8.
Food Chem ; 370: 130992, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34509946

RESUMO

The effects of dielectric barrier discharge (DBD) plasma treatment on the physicochemical properties of potato starch and its films were studied. The results showed that the plasma species caused etching lead to small cracks and pores in potato starch particles and that oxidation, de-polymerization, and crosslinking were the main mechanisms underlying the effects of DBD plasma treatment. As the treatment time extended, starch hydrolysis, turbidity, syneresis, and gelatinization temperatures increased first and then decreased, whereas the solubility, swelling power, and water absorption significantly increased (P < 0.05). There was a decrease in the retrogradation tendency of the starch gels. The surfaces of the DBD plasma-modified potato starch-based films were relatively flat. After a 9-min treatment, the films exhibited the lowest water vapor permeability and highest tensile strength. In conclusion, the use of DBD plasma is a simple and green method to enhance the properties of potato starch and its film.

9.
Environ Monit Assess ; 193(10): 643, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34508279

RESUMO

The soil environment imposes a great influence on human health. Soil heavy metal pollution caused by human activities is an important part of environmental problems in urban areas. Due to an inadequate infrastructure, imperfect management, and intensive human activities, the sources of heavy metals in urban fringe areas are often more complicated than those in other areas, such as mining areas and agricultural irrigation areas. To solve this problem, the first step is to locate the source of pollution. However, the traditional methods of source analysis, such as principal component analysis and positive matrix factorization, always require correlations between elements. This study examined the Hg, Cd, Pb, and Cu contents in the Fengdong District of Xi'an, China, and found that these elements are not correlated in this area. Hence, traditional source analysis methods are not applicable in the study area. In response to this problem, this research proposed a new source analysis method based on Pearson's correlation analysis. The Nemerow index, geoaccumulation index, and ecological risk index were adopted to evaluate soil heavy metal pollution in the study area. Via comparison to the actual situation, it was concluded that the geoaccumulation index is more suitable for source analysis in this area. Through Pearson's correlation analysis, it was found that the geoaccumulation index is significantly correlated with the various land use types. Among them, transportation land exerted a greater impact on Pb pollution, and industrial land exerted a significant impact on the Hg distribution. The Cu distribution was related to construction land, while the Cd distribution was mainly related to urban land and cultivated land. In addition, the demolition of residential areas and abandoned farmlands imposed significant effects on Pb and Cd pollution, respectively.


Assuntos
Metais Pesados , Poluentes do Solo , China , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Medição de Risco , Solo , Poluentes do Solo/análise
10.
Taiwan J Obstet Gynecol ; 60(5): 827-830, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34507656

RESUMO

OBJECTIVE: This study aims to investigate the status of fertility preservation (FP) in young breast cancer patients. MATERIALS AND METHODS: A clinical database of six women with breast cancer who wished to undergo FP before starting chemotherapy were analyzed between January 2018 and December 2019 in our hospital. Among the six women, three were unmarried and three were married. RESULTS: Three patients chose oocyte preservation and obtained 23, 7, and 17 MII oocytes, respectively. One patient chose embryo freezing, and three embryos were frozen. Fertility preservation failed for two patients, one of whom had premature ovulation, while the other patient abandoned egg retrieval on the human chorionic gonadotropin (HCG) day. CONCLUSION: The present results indicate that oocyte and embryo cryopreservation are effective optional methods for young breast cancer patients. However, a lack of knowledge, the urgency of cancer treatment, and financial constraints are causes for a low access rate regarding this process.

11.
Mol Genet Genomic Med ; : e1802, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34480426

RESUMO

BACKGROUND: Fetal cardiac rhabdomyoma (CR) is strongly associated with tuberous sclerosis complex (TSC), which is caused by variants in TSC1 and TSC2. However, in 10%-15% of patients with clinically confirmed TSC, no TSC1/TSC2 variants are identified by panel sequencing or multiplex ligation-dependent probe amplification (MLPA). METHODS: We analyzed eight fetuses with CR and their families. No TSC1/TSC2 variants had previously been identified for six of these fetuses, and we suspected the other two families of gonadal mosaicism. We performed next-generation sequencing (NGS) using CR tissue, umbilical cord tissue, and parental blood. All positive results, involving two paternal semen, were verified by droplet digital polymerase chain reaction (ddPCR). RESULTS: Four fetuses carried low-level mosaic variants (0.05%-14.89%), and two only exhibited somatic mosaic variants in the CR tissue (15.76% and 37.69%). Two fathers had gonadal mosaicism (9.07% and 4.86%). We identified nine pathogenic variants in eight fetuses, including one fetus with a second-hit variant. CONCLUSION: The fetuses assessed in this study carried low-level and somatic mosaic variants, and CR tissue from one fetus exhibited a second-hit variant. Heterozygous gonadal variants can exist in patients with low-level mosaicism. Combining NGS with ddPCR improves the accuracy of prenatal TSC diagnosis.

12.
Front Pharmacol ; 12: 686133, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34349647

RESUMO

Zishen Yutai Pills (ZYP) is a safe and well quality-controlled TCM preparation with promising effects in many fields of reproduction, including prevention of miscarriage, increase of pregnancy rate during in vitro fertilization-embryo transfer (IVF-ET). The plasma of patients was collected from a clinical trial, namely, "Effect of Traditional Chinese Medicine vs placebo on live births among women undergoing in vitro fertilization, a multi-center randomized controlled trial." Plasma samples were analyzed with metabonomics method. UPLC-MS technology was used to establish the plasma metabolic fingerprint. Multivariate statistical analysis was applied for comparing the differences of plasma metabolites between ZYP group and placebo group, 44 potential metabolites were screen out and identified. Pathway analysis was conducted with database mining. Compared with placebo, chemicals were found to be significantly down-regulated on HCG trigger day and 14 days after embryo transplantation, including trihexosylceramide (d18:1/26:1), glucosylceramide(d18:1/26:0), TG(22:6/15:0/22:6), TG(22:4/20:4/18:4). Compared with placebo, some chemicals were found to be significantly up-regulated on HCG trigger day and 14 days after embryo transplantation, i.e., PIP3(16:0/16:1), PIP2(18:1/18:1), tauroursodeoxycholic acid, L-asparagine, L-glutamic acid, kynurenic acid, 11-deoxycorticosterone, melatonin glucuronide, hydroxytyrosol. These metabolites were highly enriched in pathways including sphingolipid metabolism, alanine, aspartic acid and glutamic acid metabolism, aminoacyl tRNA biosynthesis, taurine and hypotaurine metabolism. This study revealed metabolic differences between subjects administered with ZYP and placebo. Relating metabolites were identified and pathways were enriched, providing basis on the exploration on the underlying mechanisms of ZYP combined with IVF-ET in the treatment of infertility.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34388023

RESUMO

Background: The Veterans Affairs (VA)-developed Care Assessment Need (CAN) score, a risk-stratification tool used to identify complex high-risk patients and guide VA care coordination, was designed to predict hospitalization or death. Little is known about its utility in predicting primary care utilization or if gender differences in this metric are detectable. Our objective was to determine association of CAN score quintiles with high primary care visit (PCV) utilization among Veterans, the impact of adding reproductive health and psychosocial variables to the model and the difference between men and women Veterans. Methods: The sample included men and women from the post-9/11 cohort receiving VA care for at least 1 year, 2010-2017 (N = 665,379). PCV data for each year were collected from national Corporate Data Warehouse. A cumulative count ≥6 visits in a year was used as an indication for high PCV utilization in the analyses. Results: After accounting for potential confounding factors, women were associated with 42% higher odds of heavy PCV utilization (adjusted odds ratio: 1.42, 95% confidence interval: 1.37-1.46) than men. However, there was a significant interaction between sex and CAN quintiles (p < 0.001). After adjusting for all the covariates, CAN score quintiles appeared to have stronger associations and better predictive accuracy on the risk of 1-year heavy PCV utilization for men than for women. Conclusion: Further research is needed to understand sex differences in Veterans Health Administration clinical complexity measures and whether they can be successfully used to identify high-risk, high-utilizing women Veterans.

14.
JAMA Intern Med ; 181(10): 1297-1304, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34424276

RESUMO

Importance: Neighborhood disadvantage is a novel social determinant of health that could adversely affect the functional well-being of older persons. Deficiencies in resource-poor environments can potentially be addressed through social and public health interventions. Objective: To evaluate whether estimates of active and disabled life expectancy differ on the basis of neighborhood disadvantage after accounting for individual-level socioeconomic characteristics and other prognostic factors. Design, Setting, and Participants: This prospective longitudinal cohort study included 754 nondisabled community-living persons, aged 70 years or older, who were members of the Precipitating Events Project in south central Connecticut from March 1998 to June 2020. Main Outcomes and Measures: Disability in 4 essential activities of daily living (bathing, dressing, walking, and transferring) was assessed each month. Scores on the Area Deprivation Index, a census-based socioeconomic measure with 17 education, employment, housing quality, and poverty indicators, were obtained through linkages with the 2000 Neighborhood Atlas. Area Deprivation Index scores were dichotomized at the 80th state percentile to distinguish neighborhoods that were disadvantaged (81-100) from those that were not (1-80). Results: Among the 754 participants, the mean (SD) age was 78.4 (5.3) years, and 487 (64.6%) were female. Within 5-year age increments from 70 to 90, active life expectancy was consistently lower in participants from neighborhoods that were disadvantaged vs not disadvantaged, and these differences persisted and remained statistically significant after adjustment for individual-level race and ethnicity, education, income, and other prognostic factors. At age 70 years, adjusted estimates (95% CI) for active life expectancy (in years) were 12.3 (11.5-13.1) in the disadvantaged group and 14.2 (13.5-14.7) in the nondisadvantaged group. At each age, participants from disadvantaged neighborhoods spent a greater percentage of their projected remaining life disabled, relative to those from nondisadvantaged neighborhoods, with adjusted values (SE) ranging from 17.7 (0.8) vs 15.3 (0.5) at age 70 years to 55.0 (1.7) vs 48.1 (1.3) at age 90 years. Conclusions and Relevance: In this prospective longitudinal cohort study, living in a disadvantaged neighborhood was associated with lower active life expectancy and a greater percentage of projected remaining life with disability. By addressing deficiencies in resource-poor environments, new or expanded social and public health initiatives have the potential to improve the functional well-being of community-living older persons and, in turn, reduce health disparities in the US.

15.
Front Pharmacol ; 12: 650816, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456715

RESUMO

Psoriasis is a chronic proliferative skin disorder characterised by abnormal epidermal differentiation. The Fuzhenghefuzhiyang (FZHFZY) formula created by Chuanjian Lu, a master of Chinese medicine in dermatology, has been external used in the Guangdong Provincial Hospital of Chinese Medicine for the treatment of psoriasis, but its mechanisms of action against psoriasis remain poorly understood. This study involved an exploration of the effects of FZHFZY on epidermal differentiation and its underlying mechanisms in interleukin (IL)-17A/IL-22/interferon (IFN)-γ/tumour necrosis factor (TNF)-α-stimulated HaCaT cells and in a mouse model of imiquimod (IMQ)-induced psoriasis. Cell viability was assessed by MTT assay. Epidermal differentiation was detected by reverse-transcription polymerase chain reaction and western blotting. Histological evaluation of the skin tissue was performed via haematoxylin and eosin staining, and the Akt/mTORC1/S6K1 pathway was analysed by western blotting. FZHFZY inhibited proliferation and improved epidermal differentiation in IL-17A/IL-22/IFN-γ/TNF-α-induced HaCaT cells. FZHFZY ameliorated symptoms of psoriasis, regulated epidermal differentiation and inhibited phosphorylation of the Akt/mTORC1/S6K1 pathway in the skin of mice with imiquimod-induced psoriasis. Our results suggest that FZHFZY may exhibit therapeutic action against psoriasis by regulating epidermal differentiation via inhibition of the Akt/mTORC1/S6K1 pathway.

16.
J Ethnopharmacol ; : 114456, 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34333105

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatocellular carcinoma (HCC) is a liver malignancy which lacks effective treatment and with poor prognosis. ß-Elemene refers to a series of natural Curcuma wenyujin-derived compounds, exerting lots of biological activities, which is especially famous for it's antitumor properties. AIM OF THE RESEARCH: Exploring the underlying mechanism of ß-Elemene against HCC. MATERIALS AND METHODS: MTT, the assay of Colony formation and Flow cytometric were employed to evaluate the growth of HCC and LO2 cells by ß-Elemene. HOTAIR、SP1 and PDK1 plasmids were transfected into HCC cells by transient transfection assay, and the expression and interaction of HOTAIR、SP1 and PDK1 were assessed via qRT-PCR and Western Blotting. RESULTS: ß-Elemene suppressed HCC cell growth through downregulating HOTAIR, SP1 and PDK1. Mechanism experiments proved that there existed reciprocal interaction among HOTAIR, SP1 and PDK1. Exogenously overexpressed HOTAIR or SP1 eliminated the suppressive properties of ß-Elemene on them, and both of which regulated PDK1 expression in HCC cells. Additionally, exogenously overexpressed SP1 or HOTAIR prevented ß-Elemene inhibition of the protein-level expression of PDK1, whereas overexpressing PDK1 had no effect on SP1, though it still weakened the inhibition of cell growth and HOTAIR expression by ß-Elemene. CONCLUSION: ß-Elemene suppresses HCC cell proliferation via through the regulation of HOTAIR/SP1/PDK1 axis and their interaction.

17.
Hepatology ; 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34333790

RESUMO

BACKGROUND: The hepatic venous pressure gradient (HVPG) is the standard for estimating portal pressure but requires expertise for interpretation. We hypothesized that HVPG could be extrapolated from liver histology using a machine learning (ML) algorithm. METHODS: NASH patients with compensated cirrhosis from a phase 2b trial were included. HVPG and biopsies from baseline and weeks 48 and 96 were reviewed centrally, and biopsies evaluated with a convolutional neural network (PathAI; Boston, MA). Using trichrome-stained biopsies in the training set (n=130), an ML model was developed to recognize fibrosis patterns associated with HVPG and the resultant ML HVPG score was validated in a held-out test set (n=88). Associations between the ML HVPG score with measured HVPG and liver-related events, and performance of the ML HVPG score for clinically significant portal hypertension (CSPH, HVPG ≥10 mm Hg) were determined. RESULTS: The ML HVPG score was more strongly correlated with HVPG than hepatic collagen by morphometry (ρ=0.47 vs ρ=0.28; p<0.001). The ML HVPG score differentiated patients with normal (0-5 mmHg) and elevated HVPG (5.5-9.5 mmHg), and CSPH (median: 1.51 vs 1.93 vs 2.60; all p<0.05). The AUROCs (95%CI) of the ML HVPG score for CSPH were 0.85 (0.80,0.90) and 0.76 (0.68,85) in the training and test sets, respectively. Discrimination of the ML HVPG score for CSPH improved with addition of a ML parameter for nodularity, ELF, platelets, AST, and bilirubin (AUROC in test set: 0.85;95%CI 0.78,0.92). While baseline ML HVPG score was not prognostic, changes were predictive of clinical events (HR 2.13; 95%CI 1.26,3.59) and associated with hemodynamic response and fibrosis improvement. CONCLUSIONS: A ML-model based on trichrome-stained liver biopsy slides can predict CSPH in NASH patients with cirrhosis.

18.
J Clin Sleep Med ; 2021 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-34338629

RESUMO

STUDY OBJECTIVES: Persons > 65 years with short sleep duration (≤ 6 hours) are at risk for adverse outcomes, but the accuracy of self-reported sleep duration may be affected by reduced symptom awareness. We evaluated the performance characteristics of self-reported versus objectively-measured sleep duration in this age group. METHODS: In 2,980 men from the Osteoporotic Fractures in Men Sleep Study (MrOS) and 2,855 women from the Study of Osteoporotic Fractures (SOF), we examined the agreement and accuracy of self-reported versus actigraphy-measured short and normal (> 6 but < 9 hours) sleep duration. We evaluated associations of select factors (demographics, medical, physical, and neuropsychiatric conditions, medication and substance use, and sleep-related measures) with risk of false-negative (normal sleep duration by self-report but short sleep duration by actigraphy) and false-positive (short sleep duration by self-report and normal sleep duration by actigraphy) designations, respectively, using logistic regression. RESULTS: Average ages were 76.3 ± 5.5 and 83.5 ± 3.7 years in men and women, respectively. There was poor agreement between self-reported and actigraphic sleep duration (Kappa ≤ 0.24). False-negatives occurred in nearly half and false-positives in over a quarter of older persons. In multivariable models in men and women, false-negatives were independently associated with obesity, daytime sleepiness, and napping, while false-positives were significantly lower with obesity. CONCLUSIONS: Under- and over-reporting of short sleep is common among older persons. Reliance on self-report may lead to missed opportunities to prevent adverse outcomes or unnecessary interventions. Self-reported sleep duration should be objectively confirmed when evaluating the effect of sleep duration on health outcomes.

19.
J Agric Food Chem ; 69(33): 9557-9570, 2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34382800

RESUMO

Succinate dehydrogenase inhibitors (SDHIs) have emerged in fungicide markets as one of the fastest-growing categories that are widely applied in agricultural production for crop protection. Currently, the structural modification focusing on the flexible amide link of SDHI molecules is being gradually identified as one of the innovative strategies for developing novel highly efficient and broad-spectrum fungicides. Based on the above structural features, a series of pyrazole-4-acetohydrazide derivatives potentially targeting fungal SDH were constructed and evaluated for their antifungal effects against Rhizoctonia solani, Fusarium graminearum, and Botrytis cinerea. Strikingly, the in vitro EC50 values of constructed pyrazole-4-acetohydrazides 6w against R. solani, 6c against F. graminearum, and 6f against B. cinerea were, respectively, determined as 0.27, 1.94, and 1.93 µg/mL, which were obviously superior to that of boscalid against R. solani (0.94 µg/mL), fluopyram against F. graminearum (9.37 µg/mL), and B. cinerea (1.94 µg/mL). Concurrently, the effects of the substituent steric, electrostatic, hydrophobic, and hydrogen-bond fields on structure-activity relationships were elaborated by the reliable comparative molecular field analysis and comparative molecular similarity index analysis models. Subsequently, the practical value of pyrazole-4-acetohydrazide derivative 6w as a potential SDHI was ascertained by the relative surveys on the in vivo anti-R. solani preventative efficacy, inhibitory effects against fungal SDH, and molecular docking studies. The present results provide an indispensable complement for the structural optimization of antifungal leads potentially targeting SDH.


Assuntos
Fungicidas Industriais , Succinato Desidrogenase , Botrytis , Fungicidas Industriais/farmacologia , Fusarium , Hidrazinas , Simulação de Acoplamento Molecular , Doenças das Plantas , Pirazóis/farmacologia , Relação Quantitativa Estrutura-Atividade , Rhizoctonia , Relação Estrutura-Atividade , Succinato Desidrogenase/metabolismo
20.
J Transl Med ; 19(1): 331, 2021 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-34344401

RESUMO

BACKGROUND: Biomarkers for distinguishing psoriatic arthritis (PsA) from psoriasis without arthritis (PsO) are still lacking. METHODS: We applied isobaric tags for relative and absolute quantification (iTRAQ) and LC-MS/MS to analyze the proteome profile of peripheral blood mononuclear cells (PBMCs) collected from patients with PsO, patients with PsA, and healthy controls. Bioinformatics analysis and western blotting were performed to identify and validate differentially expressed proteins. RESULTS: We identified 389, 199, 291, and 60 significantly differentially expressed proteins (adj.p < 0.05) in the comparison of all psoriatic patients versus healthy controls, PsO group versus healthy controls, PsA group versus healthy controls, and PsA group versus PsO group, respectively. Among these proteins, 14 proteins may represent promising biomarkers for PsA: SIRT2, NAA50, ARF6, ADPRHL2, SF3B6, SH3KBP1, UBA3, SCP2, RPS5, NUDT5, NCBP1, SYNE1, NDUFB7, HTATSF1. Furthermore, western blotting confirmed that SIRT2 expression was significantly higher in PBMCs from PsA patients than PsO and healthy controls, and was negatively correlated with the phosphorylation of p38 mitogen-activated protein kinase (p-p38MAPK; p = 0.006, r = - 0.582). CONCLUSIONS: This pilot study provided a broad characterization of the proteome of PBMCs in PsA as compared to PsO and healthy controls, which may help to provide prospective strategies for PsA diagnosis.


Assuntos
Artrite Psoriásica , Psoríase , Cromatografia Líquida , Glicosídeo Hidrolases , Humanos , Leucócitos Mononucleares , Projetos Piloto , Estudos Prospectivos , Proteômica , Espectrometria de Massas em Tandem
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