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The physiological and genotypic characteristics of Mangrovibacter (MGB) remain largely unexplored, including their distribution and abundance within ecosystems. M. phragmitis (MPH) ASIOC01 was successfully isolated from activated sludge (AS), which was pre-enriched by adding 1,3-dichloro-2-propanol and 3-chloro-1,2-propanediol as carbon sources. The new isolate, MPH ASIOC01, exhibited resilience in a medium containing sodium chloride concentration up to 11% (with optimal growth observed at 3%) and effectively utilizing glycerol as their sole carbon source. However, species delimitation of MGBs remains challenging due to high 16S rRNA sequence similarity (greater than 99% ANI) among different MGBs. In contrast, among the housekeeping gene discrepancies, the tryptophan synthase beta chain gene can serve as a robust marker for fast species delimitation among MGBs. Furthermore, the complete genome of MPH ASIOC01 was fully sequenced and circlized as a single contig using the PacBio HiFi sequencing method. Comparative genomics revealed genes potentially associated with various phenotypic features of MGBs, such as nitrogen-fixing, phosphate-solubilizing, cellulose-digesting, Cr-reducing, and salt tolerance. Computational analysis suggested that MPH ASIOC01 may have undergone horizontal gene transfer events, possibly contributing unique traits such as antibiotic resistance. Finally, our findings also disclosed that the introduction of MPH ASIOC01 into AS can assist in the remediation of wastewater chemical oxygen demand, which was evaluated using gas chromatograph-mass spectrometry. To the best of our knowledge, this study offers the most comprehensive understanding of the phenotypic and genotypic features of MGBs to date.
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PURPOSE: Joint destruction is a major burden and an unsolved problem in rheumatoid arthritis (RA) patients. We designed an intra-articular mesoporous silica nanosystem (MSN-TP@PDA-GlcN) with anti-inflammatory and joint protection effects. The nanosystem was synthesized by encapsulating triptolide (TP) in mesoporous silica nanoparticles and coating it with pH-sensitive polydopamine (PDA) and glucosamine (GlcN) grafting on the PDA. The nano-drug delivery system with anti-inflammatory and joint protection effects should have good potency against RA. METHODS: A template method was used to synthesize mesoporous silica (MSN). MSN-TP@PDA-GlcN was synthesized via MSN loading with TP, coating with PDA and grafting of GlcN on PDA. The drug release behavior was tested. A cellular inflammatory model and a rat RA model were used to evaluate the effects on RA. In vivo imaging and microdialysis (MD) system were used to analyze the sustained release and pharmacokinetics in RA rats. RESULTS: TMSN-TP@PDA-GlcN was stable, had good biocompatibility, and exhibited sustained release of drugs in acidic environments. It had excellent anti-inflammatory effects in vitro and in vivo. It also effectively repaired joint destruction in vivo without causing any tissue toxicity. In vivo imaging and pharmacokinetics experiments showed that the nanosystem prolonged the residence time, lowered the Cmax value and enhanced the relative bioavailability of TP. CONCLUSIONS: These results demonstrated that MSN-TP@PDA-GlcN sustained the release of drugs in inflammatory joints and produced effective anti-inflammatory and joint protection effects on RA. This study provides a new strategy for the treatment of RA.
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Antiinflamatorios , Artritis Reumatoide , Diterpenos , Liberación de Fármacos , Indoles , Nanopartículas , Fenantrenos , Polímeros , Dióxido de Silicio , Animales , Dióxido de Silicio/química , Artritis Reumatoide/tratamiento farmacológico , Nanopartículas/química , Antiinflamatorios/administración & dosificación , Antiinflamatorios/farmacología , Antiinflamatorios/química , Antiinflamatorios/farmacocinética , Fenantrenos/química , Fenantrenos/administración & dosificación , Fenantrenos/farmacocinética , Fenantrenos/farmacología , Ratas , Diterpenos/administración & dosificación , Diterpenos/química , Diterpenos/farmacocinética , Diterpenos/farmacología , Indoles/administración & dosificación , Indoles/química , Indoles/farmacocinética , Indoles/farmacología , Polímeros/química , Porosidad , Masculino , Compuestos Epoxi/química , Compuestos Epoxi/administración & dosificación , Glucosamina/química , Glucosamina/administración & dosificación , Ratas Sprague-Dawley , Portadores de Fármacos/química , Humanos , Ratones , Preparaciones de Acción Retardada , Inflamación/tratamiento farmacológico , Inflamación/prevención & controlRESUMEN
Inflammatory bowel disease (IBD) is a chronic and progressive inflammatory intestinal disease that affects people around the world. The primary cause of IBD is an imbalance in the host immune response to intestinal flora. Several human genes, including IL10, STAT3, IRGM, ATG16L1, NOD2 and RUNX3, are associated with inappropriate immune responses in IBD. It has been reported that homozygous Runx3-knockout (ko) mice spontaneously develop colitis. However, the high mortality rate in these mice within the first two weeks makes it challenging to study the role of Runx3 in colitis. To address this issue, a spontaneous colitis (SC) mouse model carrying a C-terminal truncated form of Runx3 with Tyr319stop point mutation has been generated. After weaning, SC mice developed spontaneous diarrhea and exhibited prominent enlargement of the colon, accompanied by severe inflammatory cell infiltration. Results of immunofluorescence staining showed massive CD4+ T cell infiltration in the inflammatory colon of SC mice. Colonic IL-17A mRNA expression and serum IL-17A level were increased in SC mice. CD4+ T cells from SC mice produced stronger IL-17A than those from wildtype mice in Th17-skewing conditions in vitro. In addition, the percentages of Foxp3+ Treg cells as well as the RORγt+Foxp3+ Treg subset, known for its role in suppressing Th17 response in the gut, were notably lower in colon lamina propria of SC mice than those in WT mice. Furthermore, transfer of total CD4+ T cells from SC mice, but not from wildtype mice, into Rag1-ko host mice resulted in severe autoimmune colitis. In conclusion, the C-terminal truncated Runx3 caused autoimmune colitis associated with Th17/Treg imbalance. The SC mouse model is a feasible approach to investigate the effect of immune response on spontaneous colitis.
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Colitis , Subunidad alfa 3 del Factor de Unión al Sitio Principal , Modelos Animales de Enfermedad , Linfocitos T Reguladores , Células Th17 , Animales , Células Th17/inmunología , Linfocitos T Reguladores/inmunología , Ratones , Colitis/inmunología , Colitis/inducido químicamente , Colitis/genética , Colitis/etiología , Subunidad alfa 3 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 3 del Factor de Unión al Sitio Principal/metabolismo , Ratones Noqueados , Humanos , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/etiología , Ratones Endogámicos C57BL , Interleucina-17/metabolismo , Interleucina-17/genética , Colon/patología , Colon/inmunologíaRESUMEN
BACKGROUND AND AIM: Epidemiological evidence on the relationship between exposure to volatile organic compounds (VOCs), both single and mixed, and serum lipid levels is limited, and their relationship remains unclear. Our study aimed to investigate the associations of exposure to VOCs with serum lipid levels in the US adult population. METHODS AND RESULTS: The study examined the association of 16 VOC levels (2-methylhippuric acid, 3- and 4-methylhippuric acid, N-acetyl-S-(2-carbamoylethyl)-L-cysteine, N-acetyl-S-(N-methylcarbamoyl)-L-cysteine, 2-aminothiazoline-4-carboxylic acid, N-acetyl-S-(benzyl)-L-cysteine, N-acetyl-S-(n-propyl)-L-cysteine, N-acetyl-S-(2-carboxyethyl)-L-cysteine, N-acetyl-S-(2-cyanoethyl)-L-cysteine, N-acetyl-S-(3,4-dihydroxybutyl)-L-cysteine, N-acetyl-S-(2-hydroxypropyl)-L-cysteine. N-Acetyl-S-(3-hydroxypropyl)-L-cysteine, mandelic acid, N-acetyl-S-(4-hydroxy-2-butenyl)-L-cysteine, phenylglyoxylic acid and N-acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine) with total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) using data from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2015, and a total of 1410 adults were enrolled. The association was evaluated by Bayesian kernel machine regression (BKMR), multiple linear regression and weighted quantile sum (WQS) regression. In BKMR analysis, exposure to VOCs is positively correlated with levels of TC, TG, and LDL-C. However, statistical significance was observed only for the impact on TG. Our linear regression analysis and WQS regression generally support the BKMR results. Several VOCs were positively associated with serum lipid profiles (e.g., the ln-transformed level of mandelic acid (MA) displayed an increase in estimated changes of 7.01 (95% CIs: 2.78, 11.24) mg/dL for TC level), even after the effective number of tests for multiple testing (P < 0.05). CONCLUSIONS: Exposure to VOCs was associated with serum lipids, and more studies are needed to confirm these findings.
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Compuestos Orgánicos Volátiles , Encuestas Nutricionales , Teorema de Bayes , Triglicéridos , HDL-Colesterol , AcetilcisteínaRESUMEN
"Feicheng" peach is popular for its unique aroma, but its defect of being highly sensitive to chilling injury (CI) often leads to aroma loss and internal browning. Essential oils (EOs) are often used to enhance the antioxidant capacity of plants and fruits, as well as to trigger their defense against biotic/abiotic stresses. This study aimed to examine the effect of cinnamon essential oil (CEO) vapor treatment on the aroma quality of peach fruit during cold storage using HS-GC-IMS. The results showed that 50 µL/L CEO vapor reduced the severity of internal browning (IB) in peaches at the stage of 7 ~ 21 d during refrigeration (Significantly, the L* value was higher and the IB index was lower than that of control, p < 0.05). Meanwhile, the evident reduction or loss of aroma content caused by CI was restored to a higher level than the control (p < 0.05). Furthermore, CEO treatment promoted the release of aroma-related volatiles as evidenced by more propyl acetate, and the dimer of amyl acetate, isoamyl acetate, butyl acetate detected than that on harvest day and no-treated group after 21 d of cold storage plus 2 d of shelf life. Genes of PpLOX1, PpLOX2, PpHPL1 and PpADH1 associated with aroma-related volatile biosynthesis revealed higher transcript abundance in peach fruits treated with CEO than the control (p < 0.05). Overall, our study demonstrated that CEO in vapor phase may be beneficial to alleviate the quality deterioration in aroma and flesh color of "Feicheng" peaches caused by CI, which lays a theoretical reference for maintaining postharvest quality of peach fruits.
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BACKGROUND: Cerebral vascular protection is critical for stroke treatment. Adenosine modulates vascular flow and exhibits neuroprotective effects, in which brain extracellular concentration of adenosine is dramatically increased during ischemic events and ischemia-reperfusion. Since the equilibrative nucleoside transporter-2 (Ent2) is important in regulating brain adenosine homeostasis, the present study aimed to investigate the role of Ent2 in mice with cerebral ischemia-reperfusion. METHODS: Cerebral ischemia-reperfusion injury was examined in mice with transient middle cerebral artery occlusion (tMCAO) for 90 minutes, followed by 24-hour reperfusion. Infarct volume, brain edema, neuroinflammation, microvascular structure, regional cerebral blood flow (rCBF), cerebral metabolic rate of oxygen (CMRO2), and the production of reactive oxygen species (ROS) were examined following the reperfusion. RESULTS: Ent2 deletion reduced the infarct volume, brain edema, and neuroinflammation in mice with cerebral ischemia-reperfusion. tMCAO-induced disruption of brain microvessels was ameliorated in Ent2-/- mice, with a reduced expression of matrix metalloproteinases-9 and aquaporin-4 proteins. Following the reperfusion, the rCBF of the wild-type (WT) mice was quickly restored to the baseline, whereas, in Ent2-/- mice, rCBF was slowly recovered initially, but was then higher than that in the WT mice at the later phase of reperfusion. The improved CMRO2 and reduced ROS level support the beneficial effects caused by the changes in the rCBF of Ent2-/- mice. Further studies showed that the protective effects of Ent2 deletion in mice with tMCAO involve adenosine receptor A2AR. CONCLUSIONS: Ent2 plays a critical role in modulating cerebral collateral circulation and ameliorating pathological events of brain ischemia and reperfusion injury.
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Edema Encefálico , Isquemia Encefálica , Daño por Reperfusión , Animales , Ratones , Adenosina , Edema Encefálico/tratamiento farmacológico , Edema Encefálico/patología , Isquemia Encefálica/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Enfermedades Neuroinflamatorias , Proteínas de Transporte de Nucleósidos , Especies Reactivas de Oxígeno/metabolismo , Reperfusión , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismoRESUMEN
At present, with the development of technology, the detection of cryptococcal antigen (CRAG) plays an increasingly important role in the diagnosis of cryptococcosis. However, the three major CRAG detection technologies, latex agglutination test (LA), lateral flow assay (LFA) and Enzyme-linked Immunosorbent Assay, have certain limitations. Although these techniques do not often lead to false-positive results, once this result occurs in a particular group of patients (such as human immunodeficiency virus patients), it might lead to severe consequences. CASE SUMMARY: In the three cases we reported, we found that insufficient dilution of the samples may lead to false-positive results in the detection of cryptococcal capsule antigen, which has never been reported before. CONCLUSION: Therefore, once the test results are inconsistent with the clinical symptoms, it is necessary to reexamine the samples carefully. Especially for LFA and LA, the samples can be fully diluted or segmented diluted to avoid false-positive results. It is certain that in the diagnosis, fluid and tissue culture should also be improved, combined with imaging, ink staining, and other methods to improve the accuracy of the diagnosis further.
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BACKGROUND: With the introduction of flash glucose monitoring (FGM) into the international market in 2014, academics worldwide are exploring whether this device improves glycemic control in participants with diabetes mellitus. OBJECTIVE: A study was conducted in which participants were evaluated to determine the effect of FGM on glycemic control. METHODS: From inception to April 9, 2022, we searched the Cochrane Library, PubMed, SinoMed, Embase, Web of Science, MEDLINE, CNKI, Wan Fang Data, and VIP databases to collect randomized controlled trials (RCTs) related to the effect of FGM on glycemic control in participants with diabetes mellitus. Outcomes included glycated hemoglobin, the occurrence of hypoglycemic events, fasting plasma glucose (FPG), and 2-h postprandial glucose (2hPG) levels. The statistical analysis was performed using R 4.1.3 software. RESULTS: We included 19 studies involving 2013 participants, all of which were RCTs. Meta-analysis results revealed that compared to self-monitoring of blood glucose (SMBG), FGM significantly reduced glycated hemoglobin levels in participants with type 2 diabetes mellitus [mean difference = -0.74 [95 % CI-1.16, -0.32], P < 0.01] and type 1 diabetes mellitus combined with type 2 diabetes mellitus [mean difference = -1.14 [95 % CI-3.14, 0.87], P < 0.01], with a greater effect in participants aged ≤65 years with type 2 diabetes mellitus (mean difference = -1.38 [95 % CI-2.05, -0.72], P < 0.01). However, there was no effect of FGM on the improvement of glycated hemoglobin levels in patients with type 1 diabetes mellitus [P = 0.45]. Furthermore, fasting plasma glucose levels and 2-h postprandial glucose levels were significantly lower in FGM than SMBG, and the number of hypoglycemic events was also significantly lower. CONCLUSION: Comparing SMBG with FGM indicated that FGM improves fasting plasma glucose levels, 2-h postprandial glucose levels, and glycated hemoglobin levels, and it reduces the number of hypoglycemic events.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Humanos , Hemoglobina Glucada/análisis , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/terapia , Glucemia/análisis , Control Glucémico , Ensayos Clínicos Controlados Aleatorios como Asunto , Automonitorización de la Glucosa Sanguínea/métodos , Hipoglucemiantes/uso terapéutico , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/terapiaRESUMEN
In this study, we examined excessive online gaming by adolescents and the resultant effects of their exposure to the online marketing of energy drinks and alcohol, and whether marketing literacy could serve as a mitigating factor. This cross-sectional study was conducted in 2020. Data were obtained from a sample of 2613 seventh-grade students from 30 middle schools in Taiwan. A self-administered questionnaire was conducted. The results showed that nearly 18% of the adolescent respondents had used energy drinks, while 75% reported seeing energy-drink advertisements on the internet in the past year. Multiple regression results indicated that factors such as being male, reporting excessive gaming, being exposed to higher levels of online energy-drink marketing, and reporting alcohol use were positively associated with energy-drink consumption. A higher level of online energy-drink marketing-affective literacy, however, was negatively associated with energy-drink consumption. In conclusion, factors that predicted energy-drink consumption among adolescents included excessive gaming and exposure to online energy-drink marketing, but marketing-affective literacy tended to lessen the impact of such advertising.
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Bebidas Energéticas , Juegos de Video , Adolescente , Publicidad , Estudios Transversales , Femenino , Humanos , Masculino , Mercadotecnía/métodosRESUMEN
BACKGROUND: Wernicke encephalopathy is a rare but potentially fatal adverse event caused by thiamine deficiency. Reports of non-alcoholic Wernicke encephalopathy due to malignancy are scarce in the literature, with those reported mainly being on haematological cancer, followed by gastrointestinal cancer. As a result, there is considerable under-recognition and delay in the diagnosis and treatment of Wernicke encephalopathy in oncology departments. To our knowledge, there has been no report of Wernicke encephalopathy in a patient with esophageal cancer while receiving radiotherapy. CASE SUMMARY: A 64-year-old man presented to the oncology outpatient clinic with a history of dysphagia for 2 mo, and was diagnosed with locally advanced esophageal squamous cell carcinoma (stage IIIB). Radiotherapy was initiated to alleviate dysphagia due to malignant esophageal stenosis; however, the patient exhibited consciousness disturbances starting on day 10 of radiotherapy. Brain magnetic resonance imaging indicated the development of Wernicke encephalopathy. Subsequent treatment with thiamine led to rapid improvement in the patient's neurological symptoms. CONCLUSION: Wernicke encephalopathy may develop in non-alcoholic patients undergoing radiotherapy for esophageal cancer. Early diagnosis and sufficient thiamine supplementation during radiotherapy are essential.
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Endocrine disruptors have been reported to be associated with hearing ability. However, the association between personal care and consumer product chemicals, known as commonly detected endocrine disruptors, and age-related hearing loss still remains unclear. This study aimed to examine the association between exposure to 7 personal care and consumer product chemicals and hearing thresholds in middle-aged and elderly people. A nationally representative cross-sectional study was performed. Eight hundred forty-five adults aged over 45 from the National Health and Nutrition Examination Survey (NHANES) were included in this study. Bayesian kernel machine regression (BKMR) and the k-medoid cluster analysis were used to evaluate the mixture effect of exposure to 7 chemicals on pure-tone average (PTA). Exposure to these chemicals was negatively associated with PTA. 2,5-Dichlorophenol had the greatest contribution to the mixture effect. The mixture effect was stronger in women, elderly people. Four pooled clusters were identified according to 7 chemicals exposures. Cluster 4 (high TCS exposure) showed a lower HFPTA (P = 0.00258) than cluster 3 (the lowest exposure cluster, as a reference). Our study provides evidence that exposure to personal care and consumer product chemicals might be inversely associated with PTA. More studies are needed to fully understand the association of exposure to these chemicals with hearing threshold.
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Disruptores Endocrinos , Adulto , Persona de Mediana Edad , Anciano , Humanos , Femenino , Encuestas Nutricionales , Teorema de Bayes , Estudios Transversales , AudiciónRESUMEN
BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a worldwide pandemic and significant public health issue. The effectiveness of extracorporeal membrane oxygenation (ECMO) in treating COVID-19 patients has been called into question. AIM: To conduct a meta-analysis on the mortality of COVID-19 patients who require ECMO. METHODS: This analysis adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes 2020 (PRISMA) and has been registered at the International Prospective Register of Systematic Reviews (number CRD42020227414). A quality assessment for all the included articles was performed by the Newcastle-Ottawa Scale (NOS). Studies with tenor more COVID-19 patients undergoing ECMO were included. The random-effects model was used to obtain the pooled incidence of mortality in COVID-19 patients receiving ECMO. The source of heterogeneity was investigated using subgroup and sensitivity analyses. RESULTS: We identified 18 articles with 1494 COVID-19 patients who were receiving ECMO. The score of the quality assessment ranged from 5 to 8 on the NOS. The majority of patients received veno-venous ECMO (93.7%). Overall mortality was estimated to be 0.31 [95% confidence interval (CI): 0.24-0.39; I 2 = 84.8%] based on random-effect pooled estimates. There were significant differences in mortality between location groups (33.0% vs 55.0% vs 37.0% vs 18.0%, P < 0.001), setting groups (28.0% vs 34.0%, P < 0.001), sample size (37.0% vs 31.0%, P < 0.001), and NOS groups (39.0% vs 19.0%, P < 0.001). However, both subgroup analyses based on location, setting, and sample size, and sensitivity analysis failed to identify the source of heterogeneity. The funnel plot indicated no evident asymmetry, and the Egger's (P = 0.95) and Begg's (P = 0.14) tests also revealed no significant publication bias. CONCLUSION: With more resource assessment and risk-benefit analysis, our data reveal that ECMO might be a feasible and effective treatment for COVID-19 patients.
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OBJECTIVE: It has been reported that metabolic syndrome (MetS) has been associated with hyperuricemia. However, current findings have been inconclusive regarding the direction of this association. The objective of this study was to clarify the possible directional relationship between hyperuricemia and MetS. DESIGN: This study used two waves of data from the China Health and Retirement Longitudinal Study (CHARLS) in 2011 and 2015 (N = 6,253, aged ≥40 years). Logistic regression and cross-lagged panel design were performed to evaluate the bidirectional association between uric acid with MetS. MetS score is defined as the number of MetS components present. RESULTS: New-onset hyperuricemia and MetS were observed in a four-year follow-up study among 719 and 625 participants, respectively. A positive association was observed in the adjusted logistical regression model between baseline MetS score and new-onset hyperuricemia (P for trend <0.001), and also between baseline serum uric acid (SUA) and new-onset MetS (P for trend <0.001). Cross-lagged panel analysis indicated MetS score positively and prospectively predicted SUA, but not vice versa. After stratification by sex, we observed a strong, bidirectional relationship between MetS score and SUA indicating that diagnosis in one illness increased the risk of the other, both men and women. Moreover, this study also found that systolic blood pressure (P < 0.001) and triglycerides (P < 0.001) had a bidirectional relationship with SUA. CONCLUSIONS: The results of this study indicated a bidirectional relationship between MetS and hyperuricemia.
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Hiperuricemia , Síndrome Metabólico , Adulto , China/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Hiperuricemia/complicaciones , Hiperuricemia/epidemiología , Incidencia , Estudios Longitudinales , Masculino , Jubilación , Factores de Riesgo , Ácido ÚricoRESUMEN
BACKGROUND: Trait emotional intelligence and fear of cancer recurrence could predict quality of life, but the mechanism between the three is poorly understood. METHODS: The aim of this study was to investigate the associations between trait emotional intelligence, fear of cancer recurrence and quality of life in patients with breast cancer. A cross-sectional study was conducted with 215 breast cancer patients recruited from two hospitals in China. Data were collected from December 2018 to April 2019. Questionnaires measured demographic and medical characteristics, trait emotional intelligence, fear of cancer recurrence and quality of life. Pearson correlation analysis and structural equation modelling were conducted to analyse the data. RESULTS: As expected, trait emotional intelligence was positively related to quality of life and negatively correlated with fear of cancer recurrence. Fear of cancer recurrence was negatively associated with quality of life. This relationship between trait emotional intelligence and quality of life was mediated by fear of cancer recurrence. CONCLUSIONS: These results shed light on underlying mechanisms by which trait emotional intelligence affects quality of life. Trait emotional intelligence training could reduce fear of cancer recurrence to improve quality of life for cancer patients.
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Neoplasias de la Mama , Calidad de Vida , Adaptación Psicológica , Neoplasias de la Mama/psicología , Estudios Transversales , Inteligencia Emocional , Miedo/psicología , Femenino , Humanos , Encuestas y CuestionariosRESUMEN
Dengue is one of the most prevalent arthropod-borne viral diseases in humans. There is still no effective vaccine or treatment to date. Previous studies showed that mosquito-derived factors present in saliva or salivary gland extract (SGE) contribute to the pathogenesis of dengue. In this study, we aimed to investigate the interplay between mosquito vector and DENV and to address the question of whether the mosquito vector alters the virus that leads to consequential disease manifestations in the mammalian host. DENV2 cultured in C6/36 cell line (culture-DENV2) was injected to Aedes aegypti intrathoracically. Saliva was collected from infected mosquitoes 7 days later. Exploiting the sensitivity of Stat1-/- mice to low dose of DENV2 delivered intradermally, we showed that DENV2 collected in infected mosquito saliva (msq-DENV2) induced more severe hemorrhage in mice than their culture counterpart. Msq-DENV2 was characterized by smaller particle size, larger plaque size and more rapid growth in mosquito as well as mammalian cell lines compared to culture-DENV2. In addition, msq-DENV2 was more efficient than culture-DENV2 in inducing Tnf mRNA production by mouse macrophage. Together, our results point to the possibility that the mosquito vector provides an environment that alters DENV2 by changing its growth characteristics as well as its potential to cause disease.
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Aedes/virología , Virus del Dengue/fisiología , Mosquitos Vectores/virología , Factor de Transcripción STAT1/genética , Dengue Grave/genética , Aedes/fisiología , Animales , Línea Celular , Virus del Dengue/genética , Virus del Dengue/patogenicidad , Femenino , Humanos , Masculino , Ratones , Ratones Noqueados , Mosquitos Vectores/fisiología , Factor de Transcripción STAT1/deficiencia , Dengue Grave/metabolismo , Dengue Grave/virología , Virulencia , Replicación ViralRESUMEN
Aims: Diet has been found to have an important effect on sex hormones. The effect of diet-induced inflammation on sex hormones has not been studied in detail among women. Therefore, we aimed to investigate the association between energy-adjusted dietary inflammatory index (E-DII) and sex hormones among postmenopausal women. Methods: This study used data from the National Health and Nutrition Examination Survey (NHANES) 2013-2016 waves. A total of 1183 postmenopausal women who provided information on two 24-hour dietary intake recalls, sex hormones including total testosterone (TT), estradiol (E2), TT/E2, sex hormone-binding globulin (SHBG), free estradiol (FE2) and free testosterone (FT), as well as selected covariates were included. Linear regression and restricted cubic spline evaluated the association between E-DII and sex hormones. Effect modification by body mass index (BMI) and type of menopause was then examined in stratified analysis. Results: After adjusting for covariates, linear regression showed that E-DII was positively associated with TT (P=0.035), FT (P=0.026) and TT/E2 (P=0.065). TT (P-nonlinear = 0.037) and TT/E2 (P-nonlinear = 0.035) had significant nonlinear association with E-DII. E2 (P-nonlinear = 0.046) and FE2 (P-nonlinear = 0.027) depicted a nonlinear U-shaped significant association with E-DII, the two inflection points were found at the E-DII score of -0.22 and 0.07, respectively, the associations in natural menopausal women were more pronounced. Conclusions: Our study indicates that several indicators of androgen and estrogen were associated with E-DII in postmenopausal women. Further research is needed to understand the underlying mechanisms.
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Dieta , Estradiol/sangre , Inflamación/sangre , Posmenopausia/sangre , Testosterona/sangre , Anciano , Índice de Masa Corporal , Estudios Transversales , Humanos , Persona de Mediana Edad , Encuestas Nutricionales , Globulina de Unión a Hormona Sexual/metabolismo , Estados UnidosRESUMEN
MicroRNAs (miRNAs) are small noncoding single-stranded ribonucleic acid molecules. This type of endogenous oligonucleotide could be secreted into the circulation and exist stably. The detection of specific miRNAs released by cancer cells potentially provides a noninvasive means to achieve early diagnosis and prognosis of cancers. However, the typical concentration of miRNAs in blood is below the ultratrace level. This study uses a simple thermoplastic microfluidic concentration device based on an ion concentration polarization mechanism to perform enrichment and cleanup and Raman sensing beads to determine miRNA quantitatively. One sample solution containing target miRNA molecules having been hybridized with two nucleotide probes, where one probe is on a Raman tag of a nanoaggregate embedded bead (NAEB) and the other probe is on a magnetic nanoparticle (MNP), is first filled into the device. When an external field is applied across a cation exchange membrane stationed in the middle conduit of the device, the MNP-miRNA-NAEB complexed particles are enriched near the membrane edge of the cathode side. The concentrated complexed particles are further trapped using an external magnet to perform washing steps to remove excess noncomplexed NAEBs. When cleanup steps are accomplished, the remaining complexed particles are loaded into one detection capillary to acquire Raman signals from the sensing beads. Compared with that using a conventional magnetic trapping device, the cleanup time is shortened from nearly an hour to less than 10 min. Sample loss during the washing steps becomes more controllable, resulting in adequate standard curve linearity (R > 0.99) ranging from 1 to 100 pM.
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Background: The current standard approach to the treatment of patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-sensitizing mutations has been the treatment with a first-generation EGFR-TKIs. While, with resistance developed against first-generation EGFR-TKIs, second/third-generation TKIs have attracted all the attention, and replaced first-generation EGFR- TKIs upon disease progression due to the greater efficacy and more favorable tolerability. In the past few years, this strategy has been challenged by clinical evidence when next-generation EGFR-TKIs are used in patients with advanced NSCLC. Objective: In this study, we performed a meta- analysis to investigate the efficacy of next-generation TKIs comparison with first-generation TKIs in the treatment of NSCLC. Methods: The multiple databases including Pubmed, Embase, Cochrane library databases were adopted to search for the relevant studies, and full-text articles involving to comparison of next-generation TKIs and first-generation TKIs were reviewed. After rigorous reviewing on quality, the data was extracted from eligible randomized controlled trial (RCT). Meta-analysis Revman 5.3 software was used to analyze the combined pooled ORs with the corresponding 95% confidence interval using fixed- or random-effects models according to the heterogeneity. Results: A total of 5 randomized controlled trials were included in this analysis. The group of next-generation TKIs did achieved benefit in progression-free survival (PFS) (OR = 0.58, 95%CI = 0.45-0.75, Pï¼0.0001), overall survival (OS) (OR = 0.76, 95%CI = 0.65-0.90, P = 0.001) as well with the objective response rate (ORR) (OR = 1.27, 95%CI = 1.01-1.61, P = 0.04), respectively. In the results of subgroup analysis of PFS with EGFR mutations, there is also significant differences with exon 19 deletion (OR = 0.56, 95%CI = 0.41-0.77, P = 0.0003) and exon 21 (L858R) mutation (OR = 0.60, 95%CI = 0.49-0.75, Pï¼ï¼0.00001). While, the treatment-related severe adverse event (SAE) between the next-generation TKIs and first-generation TKIs did not have statistical significance (OR = 1.48, 95%CI = 0.62-3.55, P = 0.38). Conclusion: The next-generation TKIs significantly improved efficacy outcomes in the treatment of EGFR mutation-positive advanced NSCLC compared with the first-generation TKIs, with a manageable safety profile. These results are potentially important for clinical decision making for these patients.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Supervivencia sin Enfermedad , Diseño de Fármacos , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Exones , Humanos , Neoplasias Pulmonares/mortalidad , Mutación , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
Although dengue is the most prevalent arthropod-borne viral disease in humans, no effective medication or vaccine is presently available. Previous studies suggested that mosquito salivary proteins influence infection by the dengue virus (DENV) in the mammalian host. However, the effects of salivary proteins on DENV replication within the Aedes aegypti mosquito remain largely unknown. In this study, we investigated the effect of a specific salivary protein (named AaSG34) on DENV serotype 2 (DENV2) replication and transmission. We showed that transcripts of AaSG34 were upregulated in the salivary glands of Aedes aegypti mosquitoes after a meal of blood infected with DENV2. Transcripts of the dengue viral genome and envelop protein in the salivary glands were significantly diminished after an infectious blood meal when AaSG34 was silenced. The effect of AaSG34 on DENV2 transmission was investigated in Stat1-deficient mice. The intradermal inoculation of infectious mosquito saliva induced hemorrhaging in the Stat1-deficient mice; however, saliva from the AaSG34-silenced mosquitoes did not induce hemorrhaging, suggesting that AaSG34 enhances DENV2 transmission. This is the first report to demonstrate that the protein AaSG34 promotes DENV2 replication in mosquito salivary glands and enhances the transmission of the virus to the mammalian host.
Asunto(s)
Aedes/virología , Virus del Dengue/fisiología , Dengue/transmisión , Proteínas y Péptidos Salivales/farmacología , Animales , Dengue/patología , Dengue/virología , Virus del Dengue/crecimiento & desarrollo , Femenino , Proteínas de Insectos/farmacología , Ratones Endogámicos C57BL , Ratones Noqueados , Mosquitos Vectores/virología , Interferencia de ARN , Replicación ViralRESUMEN
BACKGROUND: Although the incidence of tuberculosis (TB) has dropped substantially, it still is a serious threat to human health. And in recent years, the emergence of resistant bacilli and inadequate disease control and prevention has led to a significant rise in the global TB epidemic. It is known that the cause of TB is Mycobacterium tuberculosis infection. But it is not clear why some infected patients are active while others are latent. METHODS: We analyzed the blood gene expression profiles of 69 latent TB patients and 54 active pulmonary TB patients from GEO (Transcript Expression Omnibus) database. RESULTS: By applying minimal redundancy maximal relevance and incremental feature selection, we identified 24 signature genes which can predict the TB activation. The support vector machine predictor based on these 24 genes had a sensitivity of 0.907, specificity of 0.913, and accuracy of 0.911, respectively. Although they need to be validated in a large independent dataset, the biological analysis of these 24 genes showed great promise. CONCLUSION: We found that cytokine production was a key process during TB activation and genes like CYBB, TSPO, CD36, and STAT1 worth further investigation.