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1.
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.

2.
BMC Health Serv Res ; 19(1): 698, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615500

RESUMO

BACKGROUND: Few studies have estimated planned home deaths compared to actual place of death in a general population or the longitudinal course of home nursing services and associations with place of death. We aimed to investigate trajectories of nursing services, potentially planned home deaths regardless of place of death; and associations of place of death with potentially planned home deaths and nursing service trajectories, by analyzing data from the last 90 days of life. METHODS: A retrospective longitudinal study with data from the Norwegian Cause of Death Registry and National registry for statistics on municipal healthcare services included all community-dwelling people who died in Norway 2012-2013 (n = 53,396). We used a group-based trajectory model to identify joint trajectories of home nursing (hours per week) and probability of a skilled nursing facility (SNF) stay, each of the 13 weeks leading up to death. An algorithm estimated potentially planned home deaths. We used a multinomial logistic regression model to estimate associations of place of death with potentially planned home deaths, trajectories of home nursing and short-term SNF. RESULTS: We identified four home nursing service trajectories: no (46.5%), accelerating (7.6%), decreasing (22.1%), and high (23.5%) home nursing; and four trajectories of the probability of a SNF stay: low (69.0%), intermediate (6.7%), escalating (15.9%), and increasing (8.4%) SNF. An estimated 24.0% of all deaths were potentially planned home deaths, of which a third occurred at home. Only high home nursing was associated with increased likelihood of a home death (adjusted relative risk ratio (aRRR) 1.29; CI 1.21-1.38). Following any trajectory with elevated probability of a SNF stay reduced the likelihood of a home death. CONCLUSIONS: We estimated few potentially planned home deaths. Trajectories of home nursing hours and probability of SNF stays indicated possible effective palliative home nursing for some, but also missed opportunities of staying at home longer at the end-of-life. Continuity of care seems to be an important factor in palliative home care and home death.

3.
Glycobiology ; 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31529034

RESUMO

Glycan interactions with glycan-binding proteins (GBPs) play essential roles in a wide variety of cellular processes. Currently, the glycan specificities of GBPs are most often inferred from binding data generated using glycan arrays, wherein the GBP is incubated with oligosaccharides immobilized on a glass surface. Detection of glycan-GBP binding is typically fluorescence-based, involving the labeling of the GBP with a fluorophore or with biotin, which binds to fluorophore-labeled streptavidin, or using a fluorophore-labeled antibody that recognizes the GBP. While it is known that covalent labeling of a GBP may influence its binding properties, these effects have not been well studied and are usually overlooked when analyzing glycan array data. In the present study, electrospray ionization mass spectrometry (ESI-MS) was used to quantitatively evaluate the impact of GBP labeling on oligosaccharide affinities and specificities. The influence of three common labeling approaches, biotinylation, labeling with a fluorescent dye and introducing an iodination reagent, on the affinities of a series of human milk and blood group oligosaccharides for a C-terminal fragment of human galectin-3 was evaluated. In all cases labeling resulted in a measurable decrease in oligosaccharide affinity, by as much as 90%, and the magnitude of the change was sensitive to the nature of the ligand. These findings demonstrate that GBP labeling may affect both the absolute and relative affinities and, thereby, obscure the true glycan binding properties. These results also serve to illustrate the utility of the direct ESI-MS assay for quantitatively evaluating the effects of protein labeling on ligand binding.

4.
J Food Biochem ; 43(11): e13023, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31456257

RESUMO

This study investigated the activity of adenosine monophosphate-activated protein kinase (AMPK), glycolysis, and meat quality index in three altitude bovines during postmortem aging process. Local cattle (altitude:1,500 m), Gannan yak (3,000 m), and Yushu yak (4,500 m) postmortem Longissimus Dorsi (LD) muscle were used. Results indicated that CaCl2 significantly increased the AMPK activity by increasing the calcium-regulated protein kinase kinase (CaMKKß) activity. Besides, AMPK activation enhanced the activity of lactate dehydrogenase (LDH) and Ca2+ -ATPase and accelerated the rate of muscle maturation during postmortem aging. Moreover, the expression of HIF-1, PRKAA2, and GLUT4 genes in high-altitude Yushu yak was higher than that of low-altitude bovines. CaCl2 activates AMPK by activating CaMKKß cascade and accelerates postmortem glycolysis affecting the intramuscular environment, color, and muscle protein degradation to accelerate postmortem muscle maturation, suggesting that AMPK has essential effects on postmortem muscle glycolysis and quality, and can regulate muscle quality by regulating postmortem muscle AMPK activity. PRACTICAL APPLICATIONS: Insufficient postmortem glycolysis usually leads to DFD (dark, firm, and dry) meat. Beef have relatively high incidences of DFD meat, which has an unattractive dark color and causes significant loss to the meat industry. Therefore, AMPK, which can regulate postmortem glycolysis to affect meat quality, is a valid research target.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31406983

RESUMO

BACKGROUND: Multimorbidity has become a prominent problem worldwide; however, few population-based studies have been conducted among older Chinese with multimorbidity. This study aimed to examine the prevalence of multimorbidity and explore its common patterns among a nationally representative sample of older Chinese. METHODS: This study utilized data from the China Health and Retirement Longitudinal Study (CHARLS) and included 19,841 participants aged ≥50 years. The prevalence of individual chronic diseases and multimorbidity during 2011-2015 were evaluated among the entire cohort and according to residential regions and gender. The relationships between participants' demographic characteristics and multimorbidity were examined using logistic regression model. Patterns of multimorbidity were explored using hierarchical cluster analysis (HCA) and association rule mining (ARM). RESULTS: Multimorbidity occurred in 42.4% of the participants. The prevalence of multimorbidity was higher among women (OR=1.31, 95%CI: 1.13-1.51) and urban residents (OR=1.14, 95% CI: 1.02-1.27) than their respective counterparts after accounting for potential confounders of age, education, smoking and alcohol consumption. HCA revealed four common multimorbidity patterns: the vascular-metabolic cluster; the stomach-arthritis cluster; the cognitive-emotional cluster; and the hepatorenal cluster. Regional differences were found in the distributions of stroke and memory-related disease. Most combinations of conditions and urban-rural difference in multimorbidity patterns from HCA were also observed in ARM. CONCLUSION: The prevalence and patterns of multimorbidity vary by gender and residential regions among older Chinese. Women and urban residents are more vulnerable to multimorbidity. Future studies are needed to understand the mechanisms underlying the identified multimorbidity patterns and their policy and interventional implications.

6.
J Am Geriatr Soc ; 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31390046

RESUMO

OBJECTIVE: To examine the epidemiology and key demographic and clinical correlates of patient-reported hypersomnia in persons with advanced age. DESIGN: Cross-sectional design. SETTING: Community. PARTICIPANTS: A total of 357 community-dwelling persons from the Yale Precipitating Events Project with a mean age of 84.2 years (range = 78-102 years). MEASUREMENTS: We studied patient-reported hypersomnia, defined categorically by an Epworth Sleepiness Scale (ESS) score of 10 or greater; as well as the severity of hypersomnia symptoms, defined continuously by an ESS score range of 0 to 24 (higher scores denote greater sleepiness). In multivariable regression models, we examined cross-sectional associations between key correlates and ESS score, expressed as categorical and continuous variables. Key correlates included: demographics, education, smoking status, body mass index, self-reported medical conditions, Center for Epidemiologic Studies Depression score, Mini-Mental State Examination score, Physical Activity Scale for the Elderly, restless legs syndrome (RLS), self-reported sleep-disordered breathing (SDB), medications, and Insomnia Severity Index. RESULTS: Mean ESS score for all participants was 6.4. Patient-reported hypersomnia (ESS score ≥10) was established in 82 participants (23.0%)-their mean ESS score was 13.0. In multivariable models, male sex, nonwhite race, arthritis, depressive symptoms, low physical activity, RLS, SDB, central nervous system depressant medications, and insomnia severity were cross-sectionally associated with patient-reported hypersomnia (higher adjusted odds ratios, ranging from 1.93-2.86) and/or with the severity of hypersomnia symptoms (higher ESS scores, ranging from 0.11-2.86 points). CONCLUSION: Patient-reported hypersomnia was prevalent in a sample of community-dwelling persons with advanced age. In addition, based on cross-sectional associations with the ESS score, key demographic and clinical characteristics were identified that may inform screening strategies for hypersomnia in advanced age.

7.
Nat Prod Res ; : 1-8, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31264473

RESUMO

Two new 23, 27-dihydroxy-oleanane-type triterpenoid saponins named Raddeanoside Rf and Raddeanoside Rg (1 and 2), along with thirteen known triterpenoid saponins (3-15) were isolated from the rhizome of Anemone raddeana Regel. Their structures were determined by chemical and spectral analysis, including 1 D, 2 D NMR data and HRESIMS. The type of aglycone 23, 27-dihydroxy oleanolic acid is extremely rare in natural products. In addition, the anti-cancer activity for all the compounds were evaluated. Compounds 9 and 10 exhibited significant cytotoxicity with IC50 values of 4.47 and 8.97 µM against human pancreatic cancer lines (PANC-1), while compound 6 with IC50 value of 8.19 µM against human lung lines (A549). The possible structure-activity relationships of these triterpenoid saponins were also tentatively discussed.

8.
Hepatology ; 70(5): 1521-1530, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31271665

RESUMO

Accurate noninvasive tests (NITs) are needed to replace liver biopsy for identifying advanced fibrosis caused by nonalcoholic steatohepatitis (NASH). We analyzed screening data from two phase 3 trials of selonsertib to assess the ability of NITs to discriminate advanced fibrosis. Centrally read biopsies from the STELLAR studies, which enrolled patients with bridging fibrosis and compensated cirrhosis, were staged according to the NASH Clinical Research Network classification. We explored associations between fibrosis stage and NITs, including the nonalcoholic fatty liver disease fibrosis score (NFS), fibrosis-4 (FIB-4) index, Enhanced Liver Fibrosis (ELF) test, and liver stiffness by vibration-controlled transient elastography (LS by VCTE). The performance of these tests to discriminate advanced fibrosis, either alone or in combinations, was evaluated using areas under the receiver operating characteristic curve (AUROCs) with 5-fold cross-validation repeated 100 times. Of the 4,404 patients screened for these trials, 3,202 had evaluable biopsy data: 940 with F0-F2 fibrosis and 2,262 with F3-F4 fibrosis. Significant differences between median values of NITs for patients with F0-F2 versus F3-F4 fibrosis were observed: -0.972 versus 0.318 for NFS, 1.18 versus 2.20 for FIB-4, 9.22 versus 10.39 for ELF, and 8.8 versus 16.5 kPa for LS by VCTE (all P < 0.001). AUROCs ranged from 0.75 to 0.80 to discriminate advanced fibrosis. FIB-4 followed by an LS by VCTE or ELF test in those with indeterminate values (FIB-4 between 1.3 and 2.67) maintained an acceptable performance while reducing the rate of indeterminate results. Conclusion: Among patients being considered for enrollment into clinical trials, NITs alone or in combination can reduce the need for liver biopsy to discriminate advanced fibrosis caused by NASH. The predictive value of these tests for general screening will require confirmation in a real-world population.

9.
Nat Commun ; 10(1): 3086, 2019 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-31300655

RESUMO

Mammalian fertilisation begins when sperm interacts with the egg zona pellucida (ZP), whose ZP1 subunit is important for fertility by covalently cross-linking ZP filaments into a three-dimensional matrix. Like ZP4, a structurally-related component absent in the mouse, ZP1 is predicted to contain an N-terminal ZP-N domain of unknown function. Here we report a characterisation of ZP1 proteins carrying mutations from infertile patients, which suggests that, in human, filament cross-linking by ZP1 is crucial to form a stable ZP. We map the function of ZP1 to its ZP-N1 domain and determine crystal structures of ZP-N1 homodimers from a chicken homolog of ZP1. These reveal that ZP filament cross-linking is highly plastic and can be modulated by ZP1 fucosylation and, potentially, zinc sparks. Moreover, we show that ZP4 ZP-N1 forms non-covalent homodimers in chicken but not in human. Together, these data identify human ZP1 cross-links as a promising target for non-hormonal contraception.


Assuntos
Infertilidade Feminina/genética , Domínios Proteicos/fisiologia , Glicoproteínas da Zona Pelúcida/metabolismo , Zona Pelúcida/metabolismo , Animais , Galinhas , Cristalografia por Raios X , Feminino , Fertilização/fisiologia , Mutação da Fase de Leitura , Humanos , Simulação de Dinâmica Molecular , Multimerização Proteica , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/ultraestrutura , Alinhamento de Sequência , Glicoproteínas da Zona Pelúcida/genética , Glicoproteínas da Zona Pelúcida/isolamento & purificação , Glicoproteínas da Zona Pelúcida/ultraestrutura
10.
Medicine (Baltimore) ; 98(29): e16544, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335736

RESUMO

To investigate the status of percutaneous coronary intervention (PCI) in elderly patients with acute myocardial infarction (AMI) and analyze the reasons for not receiving PCI.A cohort of 387 consecutive hospitalized AMI patients aged ≥80 years were recruited from 2005 to 2014. Their clinical data were collected and analyzed.Among 387 elderly patients with AMI (190 men and 197 women, mean age 84.1 ±â€Š3.9 years), there were 171 patients with ST-elevation myocardial infarction (STEMI) and 216 patients with non-ST-elevation myocardial infarction (NSTEMI). The emergency and elective PCI treatment rate was 40.6% and 12.1%, respectively, in patients with STEMI; and 1% and 18%, respectively, in patients with NSTEMI. PCI treatment rate of elderly AMI patients enrolled after 2009 showed no significant difference compared to that before 2009 (P > .05). The in-hospital mortality decreased significantly in PCI treatment group. After adjustment for age, sex, and other factors, PCI treatment was identified as the independent protective factors for in-hospital mortality (odds ratio = 0.323, 95% confidence interval 0.147-0.710, P = .005). The main influence factors for not receiving PCI treatment were hemorrhage, severe renal dysfunction, infection, or severe anemia-associated complications, whereas delayed treatment was the important reason for patients not undergoing emergency PCI.PCI treatment is the independent protective factor for in-hospital mortality of elderly patients with AMI. Due to various complications, PCI treatment rate is still low in elderly patients with AMI and has not been improved recently. Paying attention to performing PCI treatment for elderly patients with AMI has positive significance.


Assuntos
Infarto do Miocárdio sem Supradesnível do Segmento ST/cirurgia , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Idoso de 80 Anos ou mais , Anemia/complicações , China , Procedimentos Cirúrgicos Eletivos , Serviço Hospitalar de Emergência , Feminino , Hemorragia/complicações , Mortalidade Hospitalar , Humanos , Infecção/complicações , Nefropatias/complicações , Masculino , Infarto do Miocárdio sem Supradesnível do Segmento ST/complicações , Infarto do Miocárdio sem Supradesnível do Segmento ST/mortalidade , Intervenção Coronária Percutânea/efeitos adversos , Complicações Pós-Operatórias , Infarto do Miocárdio com Supradesnível do Segmento ST/complicações , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Centros de Atenção Terciária , Tempo para o Tratamento
11.
Commun Biol ; 2: 268, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31341967

RESUMO

Glycan binding by glycan-binding proteins and processing by carbohydrate-active enzymes is implicated in physiological and pathophysiological processes. Comprehensive mapping of glycan interactions is essential to understanding of glycan-mediated biology and can guide the development of new diagnostics and therapeutics. Here, we introduce the competitive universal proxy receptor assay (CUPRA), which combines electrospray ionization mass spectrometry, competitive binding and heterobifunctional glycan-based ligands to give a quantitative high-throughput method for screening glycan libraries against glycan-binding and glycan-processing proteins. Application of the assay to human (siglec-2), plant (Sambucus nigra and Maackia amurensis lectins) and bacterial (cholera toxin, and family 51 carbohydrate binding module) proteins allowed for the identification of ligands with affinities (K d) ≤ 1 mM. The assay is unprecedentedly versatile and can be applied to natural libraries and, when implemented in a time-resolved manner, provides a quantitative measure of the activities and substrate specificity of carbohydrate-active enzymes.

12.
Biomed Chromatogr ; 33(10): e4624, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31215046

RESUMO

Cimicifugae Rhizoma (sheng ma) is a well-known traditional Chinese medicine, which has been demonstrated to possess anti-inflammatory, antipyretic and analgesic activities. In the present study, a simple and efficient HPLC-DAD (high-performance liquid chromatography coupled with diode array detection) method was developed and validated for simultaneous quantification of 19 chemical components (including 16 phenolic acids, one coumarin and two alkaloids) in Cimicifugae Rhizoma. The result indicated that this method could effectively evaluate the quality of Cimicifugae Rhizoma and provide a valuable reference for further study. Additionally, the antioxidant activity of Cimicifugae Rhizoma was evaluated by DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging assay. The results showed that the content of phenolic acids and antioxidant activity exhibited significant correlation coefficients.

13.
Am J Physiol Gastrointest Liver Physiol ; 317(1): G51-G56, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31091148

RESUMO

The pathophysiology of colonic diverticulosis has not been completely understood. The development of appropriate animal models is essential to study diverticular disease. To date, no large animal models are available for this disease condition. The objective of this study was to develop a swine model by damaging the colon wall, combined with or without a low-fiber diet to mimic the pathogenesis of diverticulosis. To create a weakness on the colon wall, collagenase was applied in vivo to degrade the collagen in the colon wall. Three groups of Yucatan minipigs were included. Group 1 (n = 12) underwent collagenase injection (CI) with a low-fiber diet for 6 mo, group 2 (n = 8) underwent CI alone with a standard swine diet for 6 mo, and group 3 (n = 12) received a low-fiber diet alone for 6 mo. We found that diverticulosis occurred in 91.7% (11 of 12) of pigs in the CI + diet group and 100% (8 of 8) in CI-alone group. Moreover, around 30-75% of colon CI spots for each pig developed diverticular lesions. Diet alone for 6 mo did not induce diverticulosis. The endoscopic and histological examinations revealed the formation of multiple wide-mouthed diverticular lesions along the descending colon. Our results provide convincing evidence of the high efficacy of the reduced colon wall strength caused by CI in the development of a swine model of diverticulosis. Low-fiber diet consumption for 6 mo had no influence on the generation time or incidence rate of diverticulosis. In this model, digestion of the collagen in the colonic wall is sufficient to cause diverticulosis. NEW & NOTEWORTHY Effective large animal models of diverticulosis are currently lacking for the study of diverticular disease. This study marks the first time that a swine model of diverticulosis was developed by damaging colon wall structure, combined with or without a low-fiber diet. We found that a defect of colon wall could result in colon diverticular lesions within 6 mo in swine. This animal model mimicking the pathological process of diverticulosis is of great clinical value.

14.
Sci Adv ; 5(5): eaau0495, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31086810

RESUMO

Pathological cardiac hypertrophy eventually leads to heart failure without adequate treatment. The immunoproteasome is an inducible form of the proteasome that is intimately involved in inflammatory diseases. Here, we found that the expression and activity of immunoproteasome catalytic subunit ß5i were significantly up-regulated in angiotensin II (Ang II)-treated cardiomyocytes and in the hypertrophic hearts. Knockout of ß5i in cardiomyocytes and mice markedly attenuated the hypertrophic response, and this effect was aggravated by ß5i overexpression in cardiomyocytes and transgenic mice. Mechanistically, ß5i interacted with and promoted ATG5 degradation thereby leading to inhibition of autophagy and cardiac hypertrophy. Further, knockdown of ATG5 or inhibition of autophagy reversed the ß5i knockout-mediated reduction of cardiomyocyte hypertrophy induced by Ang II or pressure overload. Together, this study identifies a novel role for ß5i in the regulation of cardiac hypertrophy. The inhibition of ß5i activity may provide a new therapeutic approach for hypertrophic diseases.

15.
BMC Infect Dis ; 19(1): 435, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31101079

RESUMO

BACKGROUND: Over the past decades there have been outbreaks of mumps in many countries, even in populations that were vaccinated. Some studies suggest that the incidence of mumps is related to meteorological changes, but the results of these studies vary in different regions. To date there is no reported study on correlations between mumps incidence and meteorological parameters in Beijing, China. METHODS: A time series analysis incorporating selected weather factors and the number of mumps cases from 1990 to 2012 in Beijing was performed. First, correlations between meteorological variables and the number of mumps cases were assessed. A seasonal autoregressive integrated moving average model with explanatory variables (SARIMAX) was then constructed to predict mumps cases. RESULTS: Mean temperature, rainfall, relative humidity, vapor pressure, and wind speed were significantly associated with mumps incidence. After constructing the SARIMAX model, mean temperature at lag 0 (ß = 0.016, p < 0.05, 95% confidence interval 0.001 to 0.032) was positively associated with mumps incidence, while vapor pressure at lag 2 (ß = -0.018, p < 0.05, 95% confidence interval -0.038 to -0.002) was negatively associated. SARIMAX (1, 1, 1) (0, 1, 1)12 with temperature at lag 0 was the best predictive construct. CONCLUSIONS: The incidence of mumps in Beijing from 1990 to 2012 was significantly correlated with meteorological variables. Combining meteorological variables, a predictive SARIMAX model that could be used to preemptively estimate the incidence of mumps in Beijing was established.


Assuntos
Caxumba/epidemiologia , Pequim/epidemiologia , Humanos , Umidade , Incidência , Análise de Séries Temporais Interrompida , Conceitos Meteorológicos , Modelos Estatísticos , Chuva , Estações do Ano , Temperatura Ambiente , Pressão de Vapor , Tempo (Meteorologia) , Vento
16.
Int Immunopharmacol ; 73: 343-352, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31129421

RESUMO

Psoriasis is a common inflammatory skin disease. Current treatment for psoriasis relies on conventional immunosuppressive agents. However, long-term treatment with global immunosuppression may cause various side effects. Thus, it is compelling to seek alternative drugs for treating psoriasis with potentially less side effects. Betulinic acid (BA) is a naturally occurring pentacyclic triterpene, an ingredient that originally exists in natural plants and lacks systemic toxicity. BA can regulate immunity with anti-fibrotic, anti-inflammatory and antioxidant properties. However, it's unknown whether BA has a therapeutic effect on psoriasis. The objectives of this study were to investigate whether BA attenuates psoriatic skin inflammation and to identify its mechanisms of action. A murine model of imiquimod-induced psoriasis was utilized to evaluate skin lesion while flow cytometry, immunohistochemistry, quantitative RT-PCR and Western blotting analyses were performed for immunoassays. We found that BA treatment alleviated psoriatic symptoms and inflammatory skin lesion. BA lowered the PASI scores, decreased epidermal thickness and reduced T cell infiltration in the skin lesion. Moreover, BA reduced the frequency of IL-17A-expressing CD4+ and γδ T cells in psoriatic mice, but did not alter CD4+FoxP3+ Treg frequency. BA also reduced IL-17A production but increased anti-inflammatory cytokine IL-10 level in serum of the psoriatic mice. Furthermore, BA inhibited gene expression of pro-inflammatory mediators in skin lesions, including RORγt, IL-17A, IL-6 and TNFα. Importantly, it suppressed NFκB signaling in the skin lesion. Finally, BA inhibited T cell proliferation and IL-17A production by CD4+ T-Cells in vitro. Thus, BA attenuates psoriasis and inhibits Th17 development.

17.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(1): 115-118, 2019 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31037913

RESUMO

OBJECTIVE: To determine risk factors associated with intraoperative blood loss in patients with early cervical cancer (stage ⅠB-ⅡA). METHODS: The medical records of 892 patients who underwent surgical treatments for early cervical cancer in the Second West China University Hospital of from Dec 2010 to Sep 2017 were retrospectively reviewed: 127 having ≥500 mL intraoperative blood loss patients compared with 765 less than 500 mL. Differences between the two groups in age, body mass index (BMI), gravidity, history of abdominal and pelvic operations, chronic pelvic inflammation disease, clinical stage, methods of operation, neoadjuvant chemotherapy (NACT) and post-NACT operative opportunity, preoperative and postoperative hemoglobin, and intraoperative transfusion volume were analyzed through univariate and multivariate statistical methods. RESULTS: The univariate analyses identified age, BMI, gravidity, history of abdominal and pelvic operation, chronic pelvic inflammation disease, clinical stage, methods of operation, NACT and post-NACT operative opportunity assignificant factors associated with intraoperative blood loss ( P<0.05). The multivariate logistic regression analysis confirmed that age ≥40 yr. [partial regression coefficient (B)=2.100)], BMI ≥24 kg/m2 (relative to 18.5-23.9 kg/m2)(B=1.842) , clinical stage ⅡA (relative to phase ⅠB, B=2.401) , trans-abdominal operative method (relative to laparoscopy, B=1.347), no NACT (B=1.540) and post-NACT operative opportunity <2 or >3 weeks (relative to within 2-3 weeks) (B=1.723) were independent predictors of higher intraoperative blood loss (≥500 mL). CONCLUSION: Clinical stage and age, etc. are risk factors associated with intraoperative blood loss in patients with early cervical cancer.


Assuntos
Neoplasias do Colo do Útero , Perda Sanguínea Cirúrgica , China , Feminino , Humanos , Histerectomia , Estadiamento de Neoplasias , Estudos Retrospectivos , Fatores de Risco
18.
Theranostics ; 9(9): 2475-2488, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31131048

RESUMO

Serum and plasma contain abundant biological information that reflect the body's physiological and pathological conditions and are therefore a valuable sample type for disease biomarkers. However, comprehensive profiling of the serological proteome is challenging due to the wide range of protein concentrations in serum. Methods: To address this challenge, we developed a novel in-depth serum proteomics platform capable of analyzing the serum proteome across ~10 orders or magnitude by combining data obtained from Data Independent Acquisition Mass Spectrometry (DIA-MS) and customizable antibody microarrays. Results: Using psoriasis as a proof-of-concept disease model, we screened 50 serum proteomes from healthy controls and psoriasis patients before and after treatment with traditional Chinese medicine (YinXieLing) on our in-depth serum proteomics platform. We identified 106 differentially-expressed proteins in psoriasis patients involved in psoriasis-relevant biological processes, such as blood coagulation, inflammation, apoptosis and angiogenesis signaling pathways. In addition, unbiased clustering and principle component analysis revealed 58 proteins discriminating healthy volunteers from psoriasis patients and 12 proteins distinguishing responders from non-responders to YinXieLing. To further demonstrate the clinical utility of our platform, we performed correlation analyses between serum proteomes and psoriasis activity and found a positive association between the psoriasis area and severity index (PASI) score with three serum proteins (PI3, CCL22, IL-12B). Conclusion: Taken together, these results demonstrate the clinical utility of our in-depth serum proteomics platform to identify specific diagnostic and predictive biomarkers of psoriasis and other immune-mediated diseases.

19.
Mol Biol Rep ; 46(4): 3857-3864, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31066003

RESUMO

Although a majority of nasopharyngeal carcinoma (NPC) are undifferentiated and strongly radiosensitive, many NPC patients still have troubles in recurrence. Traditional Chinese medicine (TCM) is considered as potential therapeutic drugs in NPC. However, the effect of Glycyrrhiza glabra on NPC is limited. The present study shows the decreased proliferation and high apoptosis in G. glabra root extract-treated C666-1 cells, indicating the anti-cancerous function of G. glabra in NPC. Then GC/MS-based metabolomics is employed to characterize variation of metabolomes in response to G. glabra root extract treatment. Metabolic category elaborates the higher percentage of down-regulated amino acids and lipids after G. glabra treatment. Moreover, ICA and pathway enrichment analysis further observe that glycine, serine and threonine metabolism, fatty acid biosynthesis, alanine, aspartate and glutamate metabolism, and cysteine and methionine metabolism are four important amino acid and lipid metabolisms that likely contribute to the anti-cancer effect of G. glabra in NPC. These pathways point out the seven metabolite biomarkers, glutathione, glutamine, L-alanine, glycine, L-serine, tetradecanoic acid and stearic acid. Taken together, these findings provide potential clues that anti-cancer mechanisms of G. glabra root extract are linked to the metabolic strategies and emphasize the significance of metabolic strategies against NPC.

20.
Heart Surg Forum ; 22(2): E165-E169, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-31013230

RESUMO

OBJECTIVE: To explore the risk factors to predict mortality among acute myocardial infarction (AMI) patients aged ≥ 80 years during their hospitalization. METHODS: A cohort of AMI patients aged ≥ 80 years hospitalized in our hospital were recruited from 2005 to 2014. Variables, including demographics, medical history, hemodynamic condition and laboratory results, were collected and analyzed to find risk factors predicting mortality during hospitalization. RESULTS: Amonga total of 384 patients enrolled in this study, the hospital mortality rate was 23.4%. By multivariable stepwise regression analysis, nine independent significant predictors associated with mortality during hospitalization were identified: history of stoke, cardiac shock, Killip class III to IV, ventricular tachycardia, pulse rate ≥ 100 bpm and EF ≤ 40% at presentation, in-hospital bleeding, initial serum creatinine concentration ≥ 177 umol/L and elevated initial WBC level. Prior angina was identified as a protective factor. Hosmer-Lemeshow test indicated good fitness of the predicting variables. CONCLUSION: Patients aged 80 and over have high mortality during hospitalization, and the risk prediction factors are clinically useful for predicting mortality in old patients with AMI.

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