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1.
Artigo em Inglês | MEDLINE | ID: mdl-32414117

RESUMO

To explore the multimorbidity prevalence and patterns among middle-aged and older adults from China. Data on thirteen chronic diseases were collected from 2,097,150 participants aged over 45 years between January 1st 2011 and December 31st 2015 from Beijing Medical Claim Data for Employees. Association rule mining and hierarchical cluster analysis were applied to assess multimorbidity patterns. Multimorbidity prevalence was 51.6% and 81.3% in the middle-aged and older groups, respectively. The most prevalent disease pair was that of osteoarthritis and rheumatoid arthritis (OARA) with hypertension (HT) (middle-aged: 22.5%; older: 41.8%). Ischaemic heart disease (IHD), HT, and OARA constituted the most common triad combination (middle-aged: 11.0%; older: 31.2%). Among the middle-aged group, the strongest associations were found in a combination of cerebrovascular disease (CBD), OARA, and HT with IHD in males (lift = 3.49), and CBD, OARA, and COPD with IHD in females (lift = 3.24). Among older patients, glaucoma and cataracts in females (lift = 2.95), and IHD, OARA, and glaucoma combined with cataracts in males (lift = 2.45) were observed. Visual impairment clusters, a mixed cluster of OARA, IHD, COPD, and cardiometabolic clusters were detected. Multimorbidity is prevalent among middle-aged and older Chinese individuals. The observations of multimorbidity patterns have implications for improving preventive care and developing appropriate guidelines for morbidity treatment.

2.
J Biomater Sci Polym Ed ; : 1-14, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32362234

RESUMO

The long circulation time and targeting drug delivery at tumor sites are still the main challenges of nanodrug delivery systems for antitumor activity. Herein, a cancer cell membrane-coated biomimetic nanodrug delivery system was fabricated. The paclitaxel (PTX)-loaded poly(lactic acid) (PLA) nanoparticles (PPNs) were used as the inner cores and 4T1 cancer cell membranes were coated on the surface of PPNs as the outer shells. The biomimetic platform was noted as CPPNs. The CPPNs exhibited proper sizes for the enhanced permeability and retention (EPR) effect and could maintain stability in a simulated physiological environment. The CPPNs exhibited a better antitumor effect than PPNs and free PTX in vitro. Moreover, due to the immune escape and homologous targeting abilities endowed by the cancer cell membrane coating, the CPPNs could efficiently accumulate and long-term exist at tumor sites. In the orthotopic 4T1 breast cancer mouse model, the CPPNs effectively inhibited the progression of tumor by increasing the apoptosis and necrosis areas within tumor tissues. In addition, the toxic side effects of PTX was also alleviated in the CPPNs group. As a result, CPPNs can be a promising biomimetic nanodrug delivery system for the enhanced and targeted therapy of breast cancer.

4.
Amino Acids ; 52(5): 823-829, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32388793

RESUMO

The change in plasma apelin level in heart failure (HF) patients is controversial. We investigated the change in plasma apelin level in HF patients versus control and non-HF patients. The plasma level of apelin was measured by ELISA and plasma level of B-type natriuretic peptide (BNP) by fluorescence immunoassay. We included 101 patients with HF, 32 patients without HF and 20 controls. The three groups did not differ in general and clinical characteristics. Plasma levels of apelin and BNP were both higher in HF patients than non-HF patients and controls. Plasma levels of apelin and BNP were not correlated. Plasma level of BNP was increased with increasing New York Heart Association grade and apelin level was decreased. Apelin level was lower in HF patients with NYHA grade IV than in controls and non-HF patients. Apelin level had 75% diagnostic value for HF, and BNP level had 96.8% diagnostic value. At a cutoff of 6.44 ng/mL apelin level, sensitivity was 69.3%, and specificity 97.1%. However, the diagnostic of apelin for NYHA II patients was higher than that of BNP (99.6% vs. 96.1%). These results suggested that apelin might be particularly useful in association with BNP in mild HF patients.

5.
Food Chem ; 326: 127001, 2020 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-32416417

RESUMO

A new food packaging material was developed for beef jerky. The material consists of an esterified potato starch film with 3 different concentrations (2%, 4%, and 6%, w/w) of sea buckthorn pomace extract. The packaged beef jerky was kept in supermarket. The sea buckthorn pomace extract-esterified potato starch film (SPF) packaging significantly reduces the water loss, L*, a*, thiobarbituric acid reactive substances (TBARS) and the total volatile basic nitrogen (TVB-N) of beef jerky during storage (p < 0.05), demonstrating a protective effect to reduce the deterioration of the quality. However, a high content of sea buckthorn pomace extract in film (6%) also affects the smell of beef jerky. Moreover, SPF effectively inhibits the growth of common spoilage bacteria in beef jerky. These results demonstrated that SPF reduces the deterioration rate of the beef jerky and the decreases the spoilage by bacteria, which both gives SPE a high potential as a new packaging material.

6.
Sci Total Environ ; 730: 139149, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32416509

RESUMO

Visibility has been continuously and stably observed for more than half a century, while particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM2.5) was not introduced to the national monitoring system in China until 2013. It is a scientific issue as to whether visibility can be used as an alternative to assess the health risks of air pollution in periods and areas without pollutant monitoring data. A generalized additive model (GAM) was adopted to estimate the impacts of seasonal changes in visibility on mortality in Beijing, China. Moreover, we estimated the contributions of particulate matter in the health effects of visibility by adjusting for dry extinction coefficient (ßdryext) and PM2.5 in the model, respectively. We found that the acute health impacts of visibility varied by season, with the highest risks in winter. For respiratory mortality, the effect estimates per 1 km decrease in visibility were 0.40% (95% CI: 0.17-0.62%) in spring, 0.10% (95% CI: -0.14-0.34%) in summer, 0.27% (95% CI: 0.09-0.45%) in autumn, and 0.62% (95% CI: 0.38-0.85%) in winter. For cardiovascular mortality, the effect estimates per 1 km decrease in visibility were 0.20% (95% CI: 0.08-0.31%) in spring, 0.16% (95% CI: 0.04-0.27%) in summer, 0.25% (95% CI: 0.13-0.37%) in autumn, and 0.24% (95% CI: 0.13-0.35%) in winter. The seasonal pattern of health impacts related to visibility reflected the seasonal variations in the characteristics of air pollution emission sources and meteorological conditions that are unfavorable for pollutant dispersion. Particulate matter, particularly PM2.5, made significant contributions to the health impacts of visibility. The results indicated that controlling pollutant emissions in winter would be of significant importance to improve air quality and mitigate the health hazard of air pollution in Beijing. Our study also provides further evidence on the feasibility of using visibility to assess the health impacts of particulate matter pollution.

7.
J Pharm Biomed Anal ; 186: 113331, 2020 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-32380350

RESUMO

Chinese medicine formula (CMF) usually contains multiple herbs and its components are very complicated, which therapeutic effects are derived from the integrative activity of multiple components. Therefore, the screening of bioactive compounds in the formula is necessary, though it is very difficult, not only for elucidating the therapeutic components but also for developing the quality control method. In this work, three cell lines fishing combined with LC-MS analysis was developed for screening the potential bioactive compounds in Fuzhengzhiyanghefuzhiyang decoction (FZHFZY), a CMF for the treatment of psoriasis in clinic. Nineteen potential active compounds were discovered and thirteen of them were identified as rehmannioside D, melittoside or rehmannioside A, tufulingoside, neoastilbin, astilbin, neoisoastilbin, isoastilbin, engeletin, isoengeletin, spinosin, cnidimoside A, rutaevin and limonin, respectively. The effects of identified components were also analyzed in vitro. The results showed that IL-1ß expression of RAW 264.7 cells treated with spinosin and melittoside as well as the TNF-α level of RAW 264.7 cells treated with rehmannioside D and melittoside were not significantly different compared with lipopolysaccharide (LPS)-treated cells. Though all identified potential active components had no apoptosis effect to HaCaT cells, rehmannioside D, rehmannioside A, astilbin and neoisoastilbin could significantly suppress HUVEC cells migration compared with control. These results indicated that the target cell fishing combined with LC-MS analysis is a useful tool for screening bioactive compounds from complicated CMF, and the identified active components may mainly contribute to the therapeutic effects of FZHFZY.

8.
Chronobiol Int ; 37(3): 438-449, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32252567

RESUMO

Objective: Findings on the effect of the lunar cycle on mental illness are conflicting. We investigated the association between the lunar cycle and a number of psychiatric presentations of schizophrenia and determined which subtypes were susceptible to lunar phases.Methods: We evaluated 13,067 patients admitted to Zhumadian Psychiatric Hospital between January 1, 2012, and December 31, 2017 (73 lunar cycles). Patients were retrospectively assigned to lunar phase based on their admission date: new moon +/- 1 day, first quarter +/- 1 day, full moon +/- 1 day, and third quarter +/- 1 day. The International Statistical Classification of Diseases, 10th revision (ICD-10), was used for diagnosis. We used a Chi-squared goodness of fit test to evaluate the distribution of admissions across the lunar phase and R*C Chi-squared tests to compare age, sex, birth season, and clinical subtype distributions by phase. We used multiple logistic regression to further identify the relationship between clinical subtype and lunar phase.Results: Psychiatric admissions for schizophrenia varied significantly across the lunar cycle (χ2 = 36.400, p< .0001), peaking in the first quarter, followed by the full moon, and lowest at the new moon. Using unspecified schizophrenia (F20.9) as reference, people with paranoid schizophrenia (F20.0) were more likely to be admitted in the full moon than in other phases (odds ratio: 1.157, 95% confidence interval: 1.040-1.286) (p < .05); other subtypes showed no admission differences during the four lunar phases (p > .05).Conclusions: Psychiatric admissions for schizophrenia show lunar periodicities. People with schizophrenia tend to be stable in the new moon, but their condition is easily aggravated during the first quarter and full moon. Patients with paranoid schizophrenia are more susceptible to deterioration at the full moon, so merit more attention and care from communities, families, and hospitals.

9.
Biosci Rep ; 40(3)2020 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-32124921

RESUMO

BACKGROUND: Alzheimer's disease (AD), which has no effective drugs to delay or prevent its progression, is a multifactorial complex neurodegenerative disease. Long non-coding RNA SOX21 antisense RNA1 (SOX21-AS1) is associated with the development of AD, but the underlying molecular mechanism of SOX21-AS1 in AD is still largely unclear. METHODS: To construct the AD model, SH-SY5Y and SK-N-SH cells were treated with amyloid-ß1-42 (Aß1-42). Quantitative real-time polymerase chain reaction (qRT-PCR) was executed to detect the expression of SOX21-AS1 and miRNA-107. Western blot analysis was utilized to assess the levels of phosphorylated Tau (p-Tau). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) or flow cytometry assay was employed to determine the viability and apoptosis of SH-SY5Y and SK-N-SH cells. The relationship between SOX21-AS1 and miRNA-107 was verified with the dual-luciferase reporter assay. RESULTS: SOX21-AS1 expression was augmented while miR-107 expression was decreased in Aß1-42-treated SH-SY5Y and SK-N-SH cells. Moreover, Aß1-42 elevated the levels of p-Tau and impeded viability and induced apoptosis of SH-SY5Y and SK-N-SH cells. Also, SOX21-AS1 silencing attenuated Aß1-42 mediated the levels of p-Tau, viability, and apoptosis of SH-SY5Y and SK-N-SH cells. Importantly, SOX21-AS1 acted as a sponge for miR-107 in SH-SY5Y and SK-N-SH cells. Furthermore, the increase in p-Tau levels and apoptosis and the repression of viability of Aß1-42-treated SH-SY5Y and SK-N-SH cells mediated by miR-107 inhibition were partly recovered by SOX21-AS1 depletion. CONCLUSION: SOX21-AS1 silencing could attenuate Aß1-42-induced neuronal damage by sponging miR-107, which provided a possible strategy for the treatment of AD.

10.
Animals (Basel) ; 10(3)2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32143283

RESUMO

To explore the postmortem physiological mechanism of muscle, activity of adenosine monophosphate activated protein kinase (AMPK) as well as its role in energy metabolism of postmortem yaks were studied. In this experiment, we injected 5-amino-1-beta-d-furanonyl imidazole-4-formamide (AICAR), a specific activator of AMPK, and STO-609 to observe the changes in glycolysis, energy metabolism, AMPK activity, and AMPK gene expression (PRKA1 and PRKA2) in postmortem yaks during maturation. The results showed that AICAR could increase the expression of the PRKKA1 and PRKAA2 genes, activate AMPK and increase its activity. The effects of AICAR include a lower concentration of ATP, an increase in AMP production, an acceleration of glycolysis, an increase in the lactic acid concentration, and a decrease in the pH value. In contrast, STO-609 had the opposite effect. Under hypoxic adaptation, the activity of the meat AMPK increased, which accelerated glycolysis and metabolism and more effectively regulated energy metabolism. Therefore, this study lays the foundation for establishing a theoretical system of energy metabolism in postmortem yak meat.

11.
Lymphat Res Biol ; 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32202948

RESUMO

Background: The goal of this study was to characterize the thoracic duct (TD) both morphologically and hemodynamically. Materials and Methods: The lymphatic flow and pressure gradient from the cisterna chyli (CC) to the lymphovenous junction were measured in anesthetized swine (n = 9). After the animals were euthanized, the TD were harvested for histomorphometric analyses in which three samples were perfused with 9% gelatin to obtain the morphometry of the TD valve in both the open and closed configuration. Spectral analyses were performed. An afferent lymphatic vessel of the CC was accessed and cannulated after the animal was euthanized for casting (n = 3) to obtain morphometric data. Results: The in vivo flow rate was 0.7 ± 0.49 mL/minute. Spectral analysis (Fast Fourier Transformation) showed correlation coefficients of 0.858 ± 0.063 and 0.586 ± 0.112 (p < 0.05) for the TD and JVPs, respectively. The average pressure gradient was 8.1 mmHg along the TD. The length of the TD was 35.6 ± 2.2 cm. The maximal width of the CC ranged from 11.4 to 15 mm. The diameter of the TD varied irregularly from 2 to 4.3 mm. The geometry of the TD leaflets was determined to have an area of 1.99 ± 0.53 mm2, a leaflet length of 3.26 ± 0.86 mm, a packet depth of 0.66 ± 0.19 mm, and a wall length of 5.46 ± 2.16 mm. The TD media thickness was ∼7 ± 3 µm. The number of valves ranged from 9 to 13 in the full length of the TD. Conclusions: A relatively constant pressure gradient in the swine TD drives lymph flow from the CC to the jugular vein. The TD is a thin-walled vessel with valves that prevent reflux of lymph flow. This study of morphometric and lymphatic dynamics is important for interventionalists to understand the anatomy and physiology of the TD to design new diagnostic, interventional procedures, and devices.

12.
J Palliat Med ; 2020 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-32119800

RESUMO

Background: Aggressive care at the end of life (EOL) is a persistent issue for patients with stage IV nonsmall cell lung cancer (NSCLC). We evaluated the use of concurrent care (CC) with hospice care and cancer-directed treatment simultaneously within the Veteran's Health Administration (VHA) and aggressive care at the EOL. Objective: To determine whether VHA facility-level CC is associated with changes in aggressive care at the EOL. Design/Setting: Veterans with stage IV NSCLC who died between 2006 and 2012 and received lung cancer care within the VHA. Measurements: The primary outcome was aggressive care at EOL (i.e., hospital admissions, chemotherapy, and intensive care unit) within the last month of life. To compare aggressive care across VHA facilities, we used a random intercept multilevel logistic regression model to examine the association between facility-level CC within each study year (<10%, 10% to 19%, and ≥20%) and aggressive care at the EOL among the decedents as a binary outcome. Results: In total, 18,371 veterans with NSCLC at 154 VHA facilities were identified. Facilities delivering CC for ≥20% of veterans (high CC) increased from 20.0% in 2006 to 43.2% in 2012 (p < 0.001). Overall, hospice care significantly increased and aggressive care at EOL decreased over the study period. However, facility-level CC adoption was not associated with any difference in aggressive care at EOL (adjusted odds ratio high CC vs. low CC: 0.91 [95% CI, 0.79 to 1.05], p = 0.21). Conclusions: Although the VHA adoption of CC increased hospice use among patients with NSCLC, additional measures may be needed to decrease aggressive care at the EOL.

13.
J Am Geriatr Soc ; 68(3): 486-495, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32083319

RESUMO

OBJECTIVES: To determine for each basic, instrumental, and mobility activity after hospitalization for acute medical illness: (1) disability prevalence immediately before and monthly for 6 months after hospitalization; (2) disability incidence 1 month after hospitalization; and (3) recovery time from incident disability during months 2 to 6 after hospitalization. DESIGN: Prospective cohort study. SETTING: New Haven, Connecticut. PARTICIPANTS: A total of 515 community-living persons, mean age 82.7 years, hospitalized for acute noncritical medical illness and alive within 1 month of hospital discharge. MEASUREMENTS: Disability was defined monthly for each basic (bathing, dressing, walking, transferring), instrumental (shopping, housework, meal preparation, taking medications, managing finances), and mobility activity (walking a quarter mile, climbing flight of stairs, lifting/carrying 10 pounds, driving) if help was needed to perform the activity or if a car was not driven in the prior month. RESULTS: Disability was common 1 and 6 months after hospitalization for activities frequently involved in leaving the home to access care including walking a quarter mile (prevalence 65% and 53%, respectively) and driving (65% and 61%). Disability was also common for activities involved in self-managing chronic health conditions including meal preparation (53% and 41%) and taking medications (41% and 31%). New disability was common and often prolonged. For example, 43% had new disability walking a quarter mile, and 30% had new disability taking medications, with mean recovery time of 1.9 months and 1.7 months, respectively. Findings were similar for the subgroup of persons residing at home (ie, not in a nursing home) at the first monthly follow-up interview after hospitalization. CONCLUSION: Disability in specific functional activities important to leaving home to access care and self-managing health conditions is common, often new, and present for prolonged time periods after hospitalization for acute medical illness. Post-discharge care should support patients through extended periods of vulnerability beyond the immediate transitional period. J Am Geriatr Soc 68:486-495, 2020.

14.
J Am Med Dir Assoc ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31928934

RESUMO

OBJECTIVES: Depressive symptoms are commonly seen among patients with multiple chronic somatic conditions, or somatic multimorbidity (SMM); however, little is known about the relationships between depressive symptoms and different SMM combinations. Our study aimed to delineate the patterns of SMM and their longitudinal associations with depressive symptoms among a nationally representative sample of middle-aged and older Chinese adults. DESIGN: We employed a longitudinal design. SETTING AND PARTICIPANTS: Older adults (N = 10,084) aged ≥45 years from the China Health and Retirement Longitudinal Study 2011-2015 participated (mean age = 57.7 years at baseline; 53.3% men). METHODS: Sixteen chronic somatic conditions were ascertained at baseline via questionnaires. Depression was assessed with the Center for Epidemiological Studies Depression Scale at baseline and during follow-up. Patterns of SMM were identified via exploratory factor analyses. Generalized estimating equations were used to evaluate the longitudinal associations between patterns of SMM and the presence of depressive symptoms at follow-up. RESULTS: Compared with participants with no somatic condition, those with 1, 2, and 3 or more somatic conditions had a 21%, 66%, and 111% greater risk, respectively, for the presence of depressive symptoms. Increased factor scores for 4 patterns identified, cardio-metabolic pattern [adjusted odds ratio (AOR) 1.12, 95% confidence interval (CI) 1.06, 1.20], respiratory pattern (AOR 1.25, 95% CI 1.17, 1.33), arthritic-digestive-visual pattern (AOR 1.29, 95% CI 1.22, 1.37), and hepatic-renal-skeletal pattern (AOR 1.09, 95% CI 1.02, 1.16), were all associated with a higher risk of having depressive symptoms. CONCLUSIONS AND IMPLICATIONS: All SMM patterns were independently associated with depression among middle-aged and older Chinese adults, with greater odds for people with comorbid arthritic-digestive-visual conditions and respiratory conditions. Clinical practitioners should treat the middle-aged and older population under a multiple-condition framework combining SMM and mental disorders.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31907523

RESUMO

BACKGROUND: Although disability is often precipitated by an illness/injury, it may arise insidiously. Our objectives were to identify the factors associated with the development of insidious and noninsidious disability and determine whether these risk factors differ between the two types of disability. METHODS: We prospectively evaluated 754 community-living persons, 70+ years, from 1998 to 2016. The unit of analysis was an 18-month person-interval, with risk factors assessed at the start of each interval. Disability in four activities of daily living and exposure to intervening events, i.e. illnesses/injuries leading to hospitalization, emergency department visits, or restricted activity, were assessed each month. Insidious and noninsidious disability were defined based on the absence and presence of an intervening event. RESULTS: The rate of noninsidious disability (21.7%) was twice that of insidious disability (10.8%). In multivariable recurrent-event Cox analyses, six factors were associated with both disability outcomes: non-Hispanic white race, lower extremity muscle weakness, poor manual dexterity, and (most strongly) frailty, cognitive impairment, and low functional self-efficacy. Three factors were associated with only noninsidious disability (older age, number of chronic conditions, and depressive symptoms), while four were associated with only insidious disability (female sex, lives with others, low SPPB score, and upper extremity weakness). The modest differences in risk factors identified for the two outcomes in multivariable analyses were less apparent in the bivariate analyses. CONCLUSIONS: Although arising from different mechanisms, insidious and noninsidious disability share a similar set of risk factors. Interventions to prevent disability should prioritize this shared set of risk factors.

16.
Med Sci Monit ; 26: e919300, 2020 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-31949123

RESUMO

BACKGROUND The aim of the present study was to investigate the clinical predictive value of pre-infarction angina (PIA) combined with mean platelet volume to lymphocyte count ratio (MPVLR) for no-reflow phenomenon and short-term mortality in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). MATERIAL AND METHODS A total of 1009 STEMI patients who had undergone PCI were enrolled and subdivided into 4 groups based on the occurrence of PIA and the presence of MPVLR above or below the cutoff value. Analysis of the predictors of the no-reflow phenomenon and 90-day mortality was conducted. Further, evaluation and comparison of the clinical predictive value of PIA, MPVLR, and their combination were done. RESULTS Both MPVLR (odds ratio [OR]=1.476, 95% confidence interval [CI]: 1.401 to 1.756, P<0.001; hazard ratio [HR]=1.430, 95% CI: 1.287 to 1.643, P<0.001) and PIA (OR=0.905, 95% CI: 0.783 to 0.986, P<0.001; HR=0.878, 95% CI: 0.796 to 0.948, P<0.001) were independent predictors of no-reflow phenomenon and 90-day mortality. Spearman's rank correlation test revealed that MPVLR (r=-0.297, P<0.001), monocyte to lymphocyte count ratio (MLR) (r=-0.211, P<0.001) and neutrophil to lymphocyte count ratio (NLR) (r=-0.389, P<0.001) in peripheral blood were significantly negatively correlated with postoperative left ventricular ejection fraction (LVEF). Upon comparing the area under curve (AUC), the MPVLR combined with PIA achieved better performance in differentiating no-reflow phenomenon (AUC=0.847, 95% CI: 0.821 to 0.874) and 90-day mortality (AUC=0.790, 95% CI: 0.725 to 0.855), than the GRACE score, MPVLR and PIA alone, and had similar performance to all other pairwise combinations of the GRACE score, MPVLR and PIA. CONCLUSIONS High MPVLR and PIA were independent predictors of the no-reflow phenomenon and 90-day mortality in patients with STEMI after PCI. Moreover, Combined application of MPVLR and PIA can effectively predict the occurrence of the no-reflow phenomenon and 90-day mortality.

17.
Anal Chem ; 92(5): 3923-3931, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-31944669

RESUMO

Interactions between glycosphingolipids (GSLs) on the surfaces of cells and glycan-binding proteins (GBPs) mediate a wide variety of essential and pathological processes. Despite the biological importance of these interactions, the GSL ligands of most GBPs remain to be identified and the mechanisms controlling recognition of GSLs are incompletely understood. Recently, it was suggested that, when present together with high affinity ligands, low affinity GSL ligands can contribute significantly to the binding of GBPs with multiple binding sites through a process called heteromultivalent binding. Here, with goal of directly establishing the existence of heteromultivalent GSL interactions and elucidating the mechanism underlying their formation, we investigated cholera toxin B subunit homopentamer (CTB5) binding to ganglioside mixtures in model membranes (nanodiscs) using native mass spectrometry (MS) and competitive ligand binding. Electrospray ionization (ESI)-MS analysis revealed that the presence of the high affinity ligand GM1 (at substoichiometric amounts relative to binding sites) in the nanodisc promotes GD1b binding to CTB5; no GD1b binding was detected in the absence of GM1. No direct ESI-MS evidence of CTB5 binding to the other five gangliosides tested, alone or present together with GM1 in the nanodiscs, was observed. Affinity measurements, carried out using the proxy ligand ESI-MS binding assay, confirmed that GD1b binding to CTB5 is dramatically enhanced (>1000-times higher affinity compared to the GD1b oligosaccharide affinity) when present with GM1. NDs containing GM1 and GM2, GD1a, or GT1b also exhibited enhanced CTB5 binding, however, the effect was smaller. The results of molecular dynamics simulations performed on ganglioside-containing nanodiscs suggest that the participation of low affinity ligands in heteromultivalent binding with GM1 may be regulated by the positions of the internal Gal-linked Neu5Ac residues of the gangliosides relative to the membrane surface.

18.
J Food Sci ; 85(1): 77-85, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31816098

RESUMO

This study aimed to explore the effect exerted by oxidative stress on apoptosis-inducing factors (AIF)-mediated apoptosis and bovine muscle tenderness during postmortem aging. We investigated the reactive oxygen species (ROS) content, mitochondrial membrane permeability, AIF expression level, nucleus apoptosis, shear force, myofibril fragmentation index, pH, and energy level. According to the results, a rise in ROS content was accompanied by the rise in mitochondrial membrane permeability from 6 to 72 hr. In the meantime, the AIF expression in mitochondria was downregulated significantly within 72 hr. However, samples treated with N-acetylcysteine had significantly lower ROS content (6 to 72 hr) and mitochondrial membrane permeability (12 to 72 hr) than the control group. Moreover, during postmortem aging, the variations in AIF levels in mitochondria were closely associated with meat tenderization and nucleus apoptosis. These findings demonstrated that oxidative stress induced by ROS significantly promoted AIF release from mitochondria by enhancing the mitochondrial membrane permeability, and the released AIF mediated nucleus apoptosis that further enhanced bovine muscle tenderness. Besides, results suggest that in the early stage, the environmental factors (ATP content and pH) significantly decreased (0 to 72 hr), whereas ROS-induced oxidative stress had no significant effect on environmental factors. These observations further suggested that during postmortem aging, the decrease of pH and ATP consumption are required by AIF release. We conclude that ROS-induced oxidative stress and internal environment are vital for meat tenderization through the regulation of AIF-mediated apoptosis pathway. PRACTICAL APPLICATION: ROS-induced oxidative stress contributes to bovine muscle tenderization by promoting cell apoptosis. It is likely to lay a theoretical foundation for developing innovative tenderization techniques by altering the internal oxidation environment of postmortem muscles.

19.
Meat Sci ; 162: 108019, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31887536

RESUMO

Yaks in high altitude regions display good adaptability to hypoxic environment. However, the mechanism involved in regulating muscle protein expression in hypoxic environment is not completely clear yet. To explore the mechanisms modulating postmortem alterations, quantitative phosphoproteomic analysis was performed on muscles of yaks raised at two different altitudes. The results indicated that 475 differentially expressed proteins (DEPS) were identified in high-altitude yaks, among which, 439 DEPs were up-regulated and 36 DEPs were down-regulated. Of these, 26 phosphoproteins clustered into energy metabolism and hypoxic adaption were selected after bioinformatics analysis. In addition, some glycolytic enzymes were detected to be differentially phosphorylated. The difference in protein phosphorylation levels between the two groups may be the key factor involved in the regulation of muscle hypoxic adaption. The present results could provide proteomic insights into changes occurring in yak muscles at different altitudes and may be a valuable resource for future investigations.

20.
Am J Hosp Palliat Care ; 37(1): 27-33, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31185722

RESUMO

BACKGROUND: Antibiotic use may increase hospital length of stay (LOS) among older patients with advanced cancer who are transitioned to comfort measures. METHODS: We studied a cohort of patients with advanced cancer aged ≥65 years who were transitioned to comfort measures during admission from July 1, 2014, through November 30, 2016. We evaluated the association between antibiotic exposure and LOS using a Poisson regression model adjusted for age, gender, cancer type, comorbidities, infection, and intensive care unit admission. RESULTS: Among 461 patients with advanced cancer, median age was 74 years (range: 65-99), 49.0% (n = 226) were female, and 20.6% (n = 95) had liquid tumors. Overall, 82.9% (n = 382) received ≥1 antibiotic and 64.6% (n = 298) had ≥1 infection diagnosis during hospitalization. Infection diagnoses commonly included sepsis (35%, n = 161/461), pneumonia (25%, n = 117/461), and urinary tract infection (14%, n = 66/461). Among those receiving antibiotics, the most common choices included vancomycin (79%, n = 300/382), cephalosporins (63%, n = 241/382), and penicillins (45%, n = 172/382). In a multivariable Poisson regression model, LOS was 34% longer (count ratio = 1.34, [95% confidence interval: 1.20-1.51]) among those exposed versus unexposed to antibiotics. CONCLUSIONS: Antibiotic use among patients with advanced cancer who are transitioned to comfort measures is associated with longer LOS. These data illustrate the importance of tradeoffs associated with antibiotic use, such as unintended increased LOS, when striving for goal-concordant care near the end of life.


Assuntos
Antibacterianos/uso terapêutico , Infecções/tratamento farmacológico , Infecções/epidemiologia , Neoplasias/epidemiologia , Neoplasias/patologia , Conforto do Paciente/organização & administração , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Comorbidade , Grupos de Populações Continentais , Feminino , Humanos , Infecções/microbiologia , Tempo de Internação , Masculino , Fatores Sexuais , Assistência Terminal/organização & administração , Fatores de Tempo
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