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OBJECTIVE: Antiphospholipid syndrome (APS) is an autoimmune disease mainly affecting young individuals. Testing for antiphospholipid antibodies is recommended for young patients who are suspected to have APS. Yet, it is hard to differentiate APS from other acquired thrombophilia disorders in elderly-onset APS patients. This study aim to investigate the characteristics and prognosis of elderly-onset APS. METHODS: This is an observational cohort study. Thrombotic APS patients who underwent follow-ups between 2009 and 2022 were included. Elderly-onset APS patients (onset age ≥60 years) were compared to non-elderly-onset APS patients (onset age <60 years) and matched cases of elderly non-APS patients (age ≥60 years with thrombosis). RESULTS: A total of 161 APS patients were included in this study, 45 (28.0%) were elderly-onset APS. Stroke (35.6% vs. 18.1%, p = .018) was more common at disease onset in elderly-onset APS patients. Compared to non-elderly-onset patients, elderly-onset APS patients were associated with a higher number of cardiovascular risk factors. Elderly-onset APS patients showed significantly lower positive rate (51.1% vs. 71.6%, p = .014) and ratios [1.24 (1.01-1.38) vs. 1.37 (1.16-1.77), p = .004] of lupus anticoagulant. Elderly-onset APS patients had a significantly higher 10-years cumulative all-cause mortality (p < .001) and APS-related mortality than non-elderly-onset patients (p = .002) and elderly non-APS patients (p = .040). CONCLUSIONS: Elderly-onset APS patients have unique disease characteristics with higher 10-years cumulative all-cause mortality and APS-related mortality. Early recognition and control of comorbidities may reduce the recurrence of thrombosis and mortality in elderly-onset APS patients.
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Walnuts have substantial economic value and are of significant interest being a wild-cultivated species. The study has re-sequenced the entire genome of the wild walnut, aligning it with the walnut reference genome, to identify 2,021,717 single nucleotide polymorphisms (SNPs). These were used to examine the genetics of 130 wild walnut samples collected from three countries. Utilizing structural and principal component analysis, the walnut samples from Central Asia were classified into four populations: Ili ah in Xinjiang (I), Dushanbe region in Tajikistan (II), Sary-Chelek, Arslanbob in Kara-Alma regions of Kyrgyzstan (III), and Kok-Tundy region of Kyrgyzstan (IV). The 4 groups showed large differences in nucleotide diversity, population differentiation, and linkage disequilibrium decay, as well as gene flow among them. The present geographic distribution of these populations does not align with the genetic distribution pattern as the populations of Central Asian wild walnuts have experienced similar population dynamics in the past, i.e., the highest effective population size at ca. 6 Ma, two sharp population declines at 6 and 0.2 Ma, and convergence at ca. 0.2 Ma. The genetic distribution patterns are better explained by human activity, notably through archaeological findings of walnut use and the influence of the Silk Road, rather than by current geographic distributions.
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INTRODUCTION: Constipation is an independent risk factor for poor bowel preparation. This study aimed to evaluate the bowel cleansing efficacy and safety of polyethylene glycol (PEG) combined with linaclotide (lin) for colonoscopy in patients with chronic constipation (CC). METHODS: This single-blinded, randomized, controlled, and multicenter study was conducted from July 2021 to December 2022 at 7 hospitals. Patients with CC who underwent colonoscopies were enrolled and randomly assigned to 4 groups with split-PEG regimens: 4L-PEG group, 4L-PEG+1d-Lin group, 3L-PEG+1d-Lin group, and 3L-PEG+3d-Lin group. The primary outcome was rates of adequate bowel preparation, defined as a total BBPS score ≥6 and a score ≥2 for each segment. Secondary outcomes were adverse effects, sleep quality, willingness to repeat the colonoscopy, adenoma detection rate, and polyp detection rate. RESULTS: Five hundred two patients were enrolled. The rates of adequate bowel preparation (80.0% vs 60.3%, P < 0.001; 84.4% vs 60.3%, P < 0.001) and the total Boston Bowel Preparation Scale (BBPS) scores (6.90 ± 1.28 vs 6.00 ± 1.61, P < 0.001; 7.03 ± 1.24 vs 6.00 ± 1.61, P < 0.01) in the 4L-PEG+1d-Lin group and the 3L-PEG+3d-Lin group were superior to that in the 4L-PEG group. Compared with the 4L-PEG group, the 4L-PEG+1d-Lin group (66.7% vs 81.7%, P = 0.008) and the 3L-PEG+3d-Lin group (75.0% vs 81.7%, P = 0.224) had a lower percentage of mild adverse events. No statistically significant difference in willingness to repeat the colonoscopy, sleep quality, polyp detection rate, or adenoma detection rate was observed among groups. DISCUSSION: PEG combined with linaclotide might be an effective method for bowel preparation before colonoscopy in patients with CC.
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Catárticos , Colonoscopía , Estreñimiento , Polietilenglicoles , Humanos , Polietilenglicoles/administración & dosificación , Polietilenglicoles/efectos adversos , Masculino , Femenino , Estreñimiento/diagnóstico , Persona de Mediana Edad , Método Simple Ciego , Catárticos/administración & dosificación , Catárticos/efectos adversos , Enfermedad Crónica , Anciano , Adulto , Péptidos/administración & dosificación , Péptidos/efectos adversos , Polvos , Resultado del Tratamiento , Electrólitos/administración & dosificación , Electrólitos/efectos adversosRESUMEN
OBJECTIVES: Ultrasound-based radiomics has demonstrated excellent diagnostic performance in differentiating benign and malignant breast masses. Given a few clinical studies on their diagnostic role, we conducted a meta-analysis of the potential effects of ultrasound-based radiomics for the differential diagnosis of breast masses, aiming to provide evidence-based medical basis for clinical research. MATERIALS AND METHODS: We searched Embase, Web of Science, Cochrane Library, and PubMed databases from inception through to February 2023. The methodological quality assessment of the included studies was performed according to Quality Assessment of Diagnostic Accuracy Studies checklist. A diagnostic test accuracy systematic review and meta-analysis was performed in accordance with PRISMA guidelines. Sensitivity, specificity, and area under curve delineating benign and malignant lesions were recorded. We also used sensitivity analysis and subgroup analysis to explore potential sources of heterogeneity. Deeks' funnel plots was used to examine the publication bias. RESULTS: A total of 11 studies were included in this meta-analysis. For the diagnosis of malignant breast masses worldwide, the overall mean rates of sensitivity and specificity of ultrasound-based radiomics were 0.90 (95% confidence interval [CI], 0.83-0.95) and 0.89 (95% CI, 0.82-0.94), respectively. The summary diagnostic odds ratio was 76 (95% CI, 26-219), and the area under the curve for the summary receiver operating characteristic curve was 0.95 (95% CI, 0.93-0.97). CONCLUSION: Ultrasound-based radiomics has the potential to improve diagnostic accuracy to discriminate between benign and malignant breast masses, and could reduce unnecessary biopsies.
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Neoplasias de la Mama , Sensibilidad y Especificidad , Ultrasonografía Mamaria , Humanos , Diagnóstico Diferencial , Neoplasias de la Mama/diagnóstico por imagen , Femenino , Ultrasonografía Mamaria/métodos , Mama/diagnóstico por imagen , RadiómicaRESUMEN
Rechargeable aqueous zinc ion batteries (ZIBs) have emerged as a promising alternative to lithium-ion batteries due to their inherent safety, abundant availability, environmental friendliness and cost-effectiveness. However, the cathodes in ZIBs encounter challenges such as structural instability, low capacity, and sluggish kinetics. In this study, we constructed BiVO4@VO2 (BVO@VO) heterojunction cathode material with bismuth vanadate and vanadium dioxide phases for ZIBs, which demonstrate significant advancements in both aqueous and quasi-solid-state ZIBs. Benefitting from the heterojunction structure, the materials present a high capacity of 262 mAh g-1 at 0.1 A g-1, superb cyclic stability with 96% capacity retention after 1000 cycles at 2 A g-1, and outstanding rate property with a specific capacity of 218 mAh g-1 even at a high rate of 5.0 A g-1. Furthermore, the flexible quasi-solid-state ZIBs incorporating the BVO@VO cathode demonstrate prolonged cyclic life performance with a remarkable specific capacity of 234 mAh g-1 over 100 cycles at a current density of 0.1 A g-1. This study potentially paves the way for the utilization of heterointerface-enhanced zinc ion diffusion for vanadium-based materials in ZIBs, thereby providing a new approach for the design and investigation of high-performance zinc-ion systems.
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Regenerating bone in the oral and maxillofacial region is clinically challenging due to the complicated osteogenic environment and the limitation of existing bone graft materials. Constructing bone graft materials with controlled degradation and stable mechanical properties in a physiological environment is of utmost importance. In this study, we used silk fibroin (SF) and polyglycolic acid (PGA) to fabricate a coaxial PGA-SF fibrous scaffold (PGA-SF-FS) to meet demands for bone grafts. The SF shell exerted excellent osteogenic activity while protecting PGA from rapid degradation and the PGA core equipped scaffold with excellent tenacity. The experiments related to biocompatibility and osteogenesis (e.g., cell attachment, proliferation, differentiation, and mineralization) demonstrated the superior ability of PGA-SF-FS to improve cell growth and osteogenic differentiation. Furthermore, in vivo testing using Sprague-Dawley rat cranial defect model showed that PGA-SF-FS accelerates bone regeneration as the implantation time increases, and its stepwise degradation helps to match the remodeling kinetics of the host bone tissue. Besides, immunohistochemical staining of CD31 and Col-1 confirmed the ability of PGA-SF-FS to enhance revascularization and osteogenesis response. Our results suggest that PGA-SF-FS fully utilizing the advantages of both components, exhibites stepwise degradation and superior tenacity in wetting regime, making it a promising candidate in the treatment of bone defects.
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Efficient removal of extremely mobile and toxic As(III) from water is a challenging but critical task. Herein, we developed a functionalized sorbent of chitosan nanofiber with iron-manganese (Fe-Mn@CS NF) using a one-step hybrid electrospinning approach to remove trace As(III) from water. Batch adsorption studies were performed to determine the adsorption efficiency under a variety of conditions, including contact time, starting concentration of As(III), ionic strength, and the presence of competing anions. The experimental results demonstrated that the concentration of As(III) dropped from 550 to less than 1.2 µg/L when using 0.5 g/L Fe-Mn@CS NF. This demonstrates the exceptional adsorption efficiency (99.8%) of Fe-Mn@CS NF for removing As(III) at pH 6.5. The kinetic tests revealed that the adsorption equilibrium was reached in 2.6 h, indicating a quick uptake of As(III). The ionic strength effect analysis showed that the adsorbed As(III) formed inner-sphere surface complexes with Fe-Mn@CS NF. The presence of SO42- or F- had a negligible impact on As(III) uptake, while the presence of PO43- impeded As(III) absorption by competing for adsorption sites. The exhausted sorbent could be effectively regenerated with a dilute NaOH solution. Even after 10 cycles of regenerating Fe-Mn@CS NF, the adsorption efficiency of As(III) in natural groundwater was maintained over 65%. XPS and FTIR analyses show that the presence of M-OH and C-O groups on the sorbent surface is essential for removing As(III) from water. Overall, our study highlights the significant potential of Fe-Mn@CS NF for the efficient and quick elimination of As(III) from water.
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This paper proposes a Pontryagin's minimum principle (PMP) energy management strategy (EMS) based on driving cycle recognition for fuel cell vehicle powertrains, aiming to minimize hydrogen consumption and fuel cell degradation. Firstly, the neural network-based driving cycle recognizer is optimized using the tuna swarm optimization (TSO) algorithm and trained under four typical driving cycles. Then, the optimal co-state variables for the four driving cycles are obtained by iteration. Finally, the co-state variables are dynamically updated based on real-time driving cycle recognition results. Comparative analysis demonstrates that the PMP-DCR effectively improves fuel cell lifetime and vehicle economy under short-distance driving cycles. Based on the combined driving cycle, the proposed PMP-DCR EMS exhibits similar economy performance to optimal dynamic programming (DP) EMS, reducing equivalent hydrogen consumption by 13.8% and 9.2%, and decreasing fuel cell degradation rates by 93% and 8.7% in comparison to the conventional power-following and PMP EMS, respectively.
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Satellite-derived Sea Surface Temperature (SST) and sea-surface Chlorophyll a concentration (Chl-a), along with Automatic Identification System (AIS) data of fishing vessels, were used in the examination of the correlation between fishing operations and oceanographic factors within the northern Indian Ocean from March 2020 to February 2023. Frequency analysis and the empirical cumulative distribution function (ECDF) were used to calculate the optimum ranges of two oceanographic factors for fishing operations. The results revealed a substantial influence of the northeast and southwest monsoons significantly impacting fishing operations in the northern Indian Ocean, with extensive and active operations during the period from October to March and a notable reduction from April to September. Spatially, fishing vessels were mainly concentrated between 20° N and 6° S, extending from west of 90° E to the eastern coast of Africa. Observable seasonal variations in the distribution of fishing vessels were observed in the central and southeastern Arabian Sea, along with its adjacent high sea of the Indian Ocean. Concerning the marine environment, it was observed that during the northeast monsoon, the suitable SST contributed to high CPUEs in fishing operation areas. Fishing vessels were widely distributed in the areas with both mid-range and low-range Chl-a concentrations, with a small part distributed in high-concentration areas. Moreover, the monthly numbers of fishing vessels showed seasonal fluctuations between March 2020 and February 2023, displaying a periodic pattern with an overall increasing trend. The total number of fishing vessels decreased due to the impact of the COVID-19 pandemic in 2020, but this was followed by a gradual recovery in the subsequent two years. For fishing operations in the northern Indian Ocean, the optimum ranges for SST and Chl-a concentration were 27.96 to 29.47 °C and 0.03 to 1.81 mg/m3, respectively. The preliminary findings of this study revealed the spatial-temporal distribution characteristics of fishing vessels in the northern Indian Ocean and the suitable ranges of SST and Chl-a concentration for fishing operations. These results can serve as theoretical references for the production and resource management of off-shore fishing operations in the northern Indian Ocean.
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Vertebrate embryogenesis is a remarkable process, during which numerous cell types of different lineages arise within a short time frame. An overwhelming challenge to understand this process is the lack of dynamic chromatin accessibility information to correlate cis-regulatory elements (CREs) and gene expression within the hierarchy of cell fate decisions. Here, we employed single-nucleus ATAC-seq to generate a chromatin accessibility dataset on the first day of zebrafish embryogenesis, including 3.3 hpf, 5.25 hpf, 6 hpf, 10 hpf, 12 hpf, 18 hpf and 24 hpf, obtained 51,620 high-quality nuclei and 23 clusters. Furthermore, by integrating snATAC-seq data with single-cell RNA-seq data, we described the dynamics of chromatin accessibility and gene expression across developmental time points, which validates the accuracy of the chromatin landscape data. Together, our data could serve as a fundamental resource for revealing the epigenetic regulatory mechanisms of zebrafish embryogenesis.
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Cromatina , Pez Cebra , Animales , Diferenciación Celular/genética , Núcleo Celular/metabolismo , Cromatina/genética , Cromatina/metabolismo , Desarrollo Embrionario/genética , Pez Cebra/genética , Pez Cebra/metabolismoRESUMEN
BACKGROUND: Clonorchis sinensis granulin (CsGRN), a component of the excretory/secretory products of this species, is a multifunctional growth factor that can promote the metastasis of cholangiocarcinoma cells. However, the effect of CsGRN on human intrahepatic biliary epithelial cells (HIBECs) is unclear. Here, we investigated the effect of CsGRN on the malignant transformation of HIBECs and its possible underlying mechanism. METHODS: The malignant transformation phenotypes of HIBECs after CsGRN treatment were estimated by EdU-488 incorporation assay, colony formation assay, wound-healing assay, Transwell assay and western blot. The biliary damage of CsGRN-treated mice was detected by western blot, immunohistochemical staining and hematoxylin and eosin staining. The phenotypes of the macrophages [human monocytic leukemia cell line (THP-1)] were analyzed by flow cytometry, immunofluorescence and immunohistochemistry, both in vitro and in vivo. A co-culture system was developed to explore the interaction between THP-1 and HIBECs in CsGRN-containing medium. Enzyme-linked immunosorbent assay and western blot were used to detected the activation of interleukin 6 (IL-6), phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. An inhibitor of the MEK/ERK pathway, PD98059, was used to determine whether this pathway is involved in CsGRN-mediated cell interactions as well as in STAT3 phosphorylation and malignant transformation of HIBECs. RESULTS: Excessive hyperplasia and abnormal proliferation of HIBECs, enhanced secretion of hepatic pro-inflammatory cytokines and chemokines, as well as biliary damage, were observed in vitro and in vivo after treatment with CsGRN. The expression of the markers of M2 macrophages significantly increased in CsGRN-treated THP-1 cells and biliary duct tissues compared with the controls. Moreover, following treatment with CsGRN, the HIBECs underwent malignant transformation in the THP-1-HIBECs co-culture group. In addition, high expression of IL-6 was observed in the CsGRN-treated co-culture media, which activated the phosphorylation of STAT3, JAK2, MEK and ERK. However, treatment with an inhibitor of the MEK/ERK pathway, PD98059, decreased expression of p-STAT3 in CsGRN-treated HIBECs and further repressed the malignant transformation of HIBECs. CONCLUSIONS: Our results demonstrated that, by inducing the M2-type polarization of macrophages and activating the IL-6/JAK2/STAT3 and MEK/ERK pathways in HIBECs, CsGRN promoted the malignant transformation of the latter.
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Neoplasias de los Conductos Biliares , Clonorchis sinensis , Humanos , Animales , Ratones , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Fosforilación , Sistema de Señalización de MAP Quinasas , Granulinas/metabolismo , Clonorchis sinensis/metabolismo , Interleucina-6/genética , Factor de Transcripción STAT3/metabolismo , Células Epiteliales/metabolismo , Macrófagos/metabolismo , Conductos Biliares Intrahepáticos , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/patología , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismoRESUMEN
OBJECTIVES: How chronic pelvic inflammatory disease (CPID), the most common cause of infertility, affects metabolic profiles of follicular fluid (FF) remains unknown. This study aimed to identify candidate biomarkers in FF of infertile women with CPID. METHOD: FF samples were collected from infertile women with CPID (n = 8) and healthy controls (n = 8) at the time of oocyte retrieval. Untargeted metabolomic profiling of FF samples was conducted using the liquid chromatography-tandem mass spectrometry (LC-MS/MS). RESULTS: A total of 240 differential metabolites (104 named biochemicals and 136 unnamed biochemicals) were screened out and identified. Among them, pregnane-3,3-diol, pc(p-18:1(11z)/18:3(6z,9z,12z)), and 1-octadecanoyl-2-(4z,7z,10z,13z,16z,19z-docosahexaenoyl)-sn-glycero-3-phosphoethanolamine were markedly down-regulated, while 17,21-dihydroxypregnenolone was significantly up-regulated in infertile women with CPID. Furthermore, KEGG biological pathway analysis revealed that these metabolites were especially enriched in steroid hormone biosynthesis, glyoxylate and dicarboxylate metabolism, glucagon signaling pathway, and the tricarboxylic acid (TCA) cycle. CONCLUSION: FF of infertile women with CPID showed unique metabolic changes that may be involved in the pathogenesis of infertility and serve as new therapeutic targets or diagnostic biomarkers.
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Per- and polyfluoroalkyl substances (PFAS) are a group of anthropogenic pollutants that are found ubiquitously in surface and drinking water supplies. Due to their persistent nature, bioaccumulative potential, and significant adverse health effects associated with low concentrations, they pose a concern for human and environmental exposure. With the advances in high-resolution mass spectrometry (HRMS) methods, there has been an increasing number of non-targeted analysis (NTA) approaches that allow for a more comprehensive characterization of total PFAS present in environmental samples. In this study, we have developed and compared NTA workflows based on an online solid phase extraction- liquid chromatography high resolution mass spectrometry (online SPE-LC-HRMS) method followed by data processing using Compound Discoverer and FluoroMatch for the screening of PFAS in drinking waters from populated counties in South Florida, as well as in surface waters from Biscayne Bay, Key west, and Everglades canals. Tap water showed the highest number of PFAS features, indicating a poor removal of these chemicals by water treatment or perhaps the breakdown of PFAS precursors. The high number of PFAS features identified only by CD and FluoroMatch emphasizes the complementary aspects of these data processing methods. A Semi-quantitation method for NTA (qNTA) was proposed using a global calibration curve based on existing native standards and internal standards, in which concentration estimates were determined by a regression-based model and internal standard (IS) response factors. NTA play a crucial role in the identification and prioritization of non-traditionally monitored PFAS, needed for the understanding of the toxicological and environmental impact, which are largely underestimated due to the lack of such information for many PFAS.
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Agua Potable , Fluorocarburos , Contaminantes Químicos del Agua , Humanos , Florida , Contaminantes Químicos del Agua/análisis , Abastecimiento de Agua , Exposición a Riesgos Ambientales/análisis , Fluorocarburos/análisis , Agua Potable/análisisRESUMEN
Herein, a novel nitr[ogen-doped carbon dot (N-CD) fluorescence sensor with a dual emission ratio is developed using the microwave-assisted synthesis of m-phenylenediamine and spermidine. As a result of the fluorescence inner filtration effect (IFE) effect between morphine (MOR) and N-CD, the blue fluorescence of N-CDs at 350 nm was reduced in the presence of MOR, whereas the fluorescence of N-CDs at 456 nm increased substantially. The results demonstrated that the approach has a tremendous potential and that the linear range of MOR detection is 0.25-25 µg/mL, with a 71.8 ng/mL detection limit. Under UV light, the blue fluorescent system is easily visible to the naked eye. More significantly, the sensor proved successful in providing satisfactory results for the speciation measurement of MOR in a variety of biological samples.
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Puntos Cuánticos , Carbono , Colorantes Fluorescentes , Espectrometría de Fluorescencia , Derivados de la MorfinaRESUMEN
Rheumatic diseases have been reported to sometimes involve the pituitary gland. This study aims to characterize the clinical features and outcomes of patients with rheumatic disease-associated hypophysitis. We used the electronic medical record system in our hospital to identify nine patients with pituitary involvement in rheumatoid disease. We summarized the clinical characteristics, radiographic findings, treatments, and clinical outcomes of the 9 patients. We also performed a systematic literature review of systemic lupus erythematosus (SLE) cases with pituitary involvement published in PubMed and Wanfang databases from 1995 to 2021, and eight patients with complete information were selected. In the nine-patient cohort, the median age was 54 years, and the spectrum of rheumatic diseases included immunoglobulin G4-related disease (IgG4RD) (4/9), SLE (2/9), vasculitis (2/9), and Sjögren syndrome (SS) (1/9). All patients had pituitary abnormalities on radiological assessment, 6 developed diabetes insipidus (DI), and 8 presented with anterior pituitary hormone deficiencies in the disease duration. All the patients had multisystem involvement. As compared to hypophysitis with IgG4RD (IgG4-H), the age at onset of hypophysitis with SLE (SLE-H) patients was younger [(30.4 ± 16.4) years vs. (56.0 ± 0.8) years] and the disease duration was shorter [(14.0 ± 17.5) months vs. (71.0 ± 60.9) months] (P < .05). All patients were managed with glucocorticoids (GC) in combination with another immunosuppressant, and the majority of patients improved within 4 months. Six patients achieved disease remission while four required at least one hormone replacement therapy. Hypophysitis is a rare complication secondary to a variety of various rheumatic diseases that can occur at any stage. GC combined with additional immunosuppressants could improve patients' symptoms; however some patients also required long-term hormone replacement therapy in pituitary disorders.
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Hipofisitis Autoinmune , Enfermedades del Colágeno , Hipofisitis , Hipopituitarismo , Lupus Eritematoso Sistémico , Enfermedades de la Hipófisis , Enfermedades Reumáticas , Humanos , Persona de Mediana Edad , Adolescente , Adulto Joven , Adulto , Hipofisitis/complicaciones , Enfermedades de la Hipófisis/complicaciones , Enfermedades de la Hipófisis/diagnóstico , Hipopituitarismo/etiología , Hipófisis/diagnóstico por imagen , Glucocorticoides/uso terapéutico , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Enfermedades del Colágeno/tratamiento farmacológico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Hipofisitis Autoinmune/complicaciones , Hipofisitis Autoinmune/diagnóstico , Hipofisitis Autoinmune/tratamiento farmacológicoRESUMEN
Albendazole (ABZ) is a broad-spectrum anti-parasitic drug that exhibits antitumor effects against several carcinomas. The effects of ABZ on cholangiocarcinoma (CCA) and its underlying mechanisms are still unclear. Our study aims to investigate the role of ABZ in inducing autophagy-mediated apoptosis of cholangiocarcinoma cells. The antitumor effects of ABZ were evaluated against CCA cells and HIBEC intrahepatic biliary epithelial cells. Furthermore, the apoptosis rates, and autophagy flux in RBE and FRH-0201 cells treated with ABZ were investigated. ABZ inhibited proliferation, induced cell death and apoptosis in CCA cells in vitro. In vivo, tumors from ABZ- treated BALB/c nude mice were significantly smaller than untreated mice. ABZ also induced the initiation of autophagy via AMPK/mTOR pathways, resulting in the formation of autophagosome. In addition, ABZ blocked autophagic flux by inhibiting the fusion of autophagosome-lysosome, which increased the apoptotic death of CCA cells. However, the apoptotic death of CCA cells induced by ABZ was reversed by 3-methyladenine (3-MA), an autophagosome formation inhibitor, but increased by chloroquine (CQ), an autophagosome-lysosome fusion inhibitor.Our work provides novel mechanisms for anti-tumor effects of ABZ on CCA, suggesting that ABZ may be used as a potent autophagy inhibitor in the treatment of CCA.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Proteínas Quinasas Activadas por AMP/metabolismo , Albendazol/farmacología , Albendazol/uso terapéutico , Animales , Apoptosis , Autofagia , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/patología , Conductos Biliares Intrahepáticos/metabolismo , Conductos Biliares Intrahepáticos/patología , Línea Celular Tumoral , Cloroquina/farmacología , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/metabolismo , Colangiocarcinoma/patología , Ratones , Ratones Desnudos , Serina-Treonina Quinasas TORRESUMEN
Per- and polyfluoroalkyl substances (PFAS) are notoriously persistent pollutants that are found ubiquitously present in aquatic environments. They pose a big threat to aquatic life and human health given the bioaccumulation feature and significant adverse health effects associated. In our previous study, PFAS were found in surface waters from Biscayne Bay and tap waters from the East coast of South Florida, at levels that arouse human health and ecological concerns. Considering that Florida supports millions population as well as treasured, sensitive coastal and wetland ecosystems, we have expanded the PFAS monitoring study on the occurrence, composition, spatial distribution, and potential sources encompassing tap waters from counties on the West coast of South Florida and Central Florida, and surface waters from Tampa Bay, Everglades National Park adjacent canals, Key West, including Biscayne Bay area. A total of 30 PFAS were analyzed based on solid-phase extraction (SPE) followed by liquid chromatography tandem mass spectrometry (LC-MS/MS). PFAS were detected in all tap water (N = 10) and surface water samples (N = 38) with total concentrations up to 169 ng L-1. Higher PFAS concentrations (> 60 ng L-1) are mostly observed from polluted rivers or coastal estuaries in Biscayne Bay, and sites nearby potential points sources (military airbases, wastewater facilities, airports, etc.). Our findings on current PFAS contamination levels from diverse aquatic environments provide additional information for the development of more stringent screening levels that are protective of human health and the environmental resources of Florida, which is ultimately anticipated as scientific understanding of PFAS is rapidly growing.
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Fluorocarburos , Contaminantes Químicos del Agua , Humanos , Fluorocarburos/análisis , Monitoreo del Ambiente/métodos , Contaminantes Químicos del Agua/análisis , Ecosistema , Cromatografía Liquida , Florida , Espectrometría de Masas en Tándem , Agua/análisisRESUMEN
OBJECTIVE: To explore the risk factors for adverse pregnancy outcomes (APOs) in women with rheumatoid arthritis (RA) and the influence on their offspring health. METHODS: Pregnant women with RA (n = 67) who were hospitalized in the Department of Obstetrics, Peking University People's Hospital between January 2007 and September 2021 were included in this study. Participants were evaluated at least once in each trimester and postpartum. Fetal outcomes and RA disease activity were extracted from medical records, and the offspring of enrolled patients were followed up. Associations between RA disease activity, medication use, and pregnancy outcomes were analyzed. RESULTS: The incidence of APOs in our cohort was 43.3%. Postpartum hemorrhage (20.9%) was the commonest complication, followed by premature delivery (11.9%). Previous miscarriages [odds ratio (OR): 1.869, 95% confidence interval (CI): 1.053-3.318, P = 0.033] and antinuclear antibody (ANA) positivity (OR:3.168, 95% CI: 1.068-9.768, P = 0.045) were risk factors for APOs. Compared to patients with APOs, the remission rate of disease activity during pregnancy was higher in patients without APOs (P = 0.027). There were no significant differences between patients with and without APOs with respect to daily and cumulative doses of prednisone (P > 0.05). The average age of the offspring was 4.9 years (range 0.3-14 years). Long-term follow-up showed no significant differences in offspring health between the two groups (P > 0.05). CONCLUSION: Previous miscarriages and ANA positivity are independent risk factors for APOs in RA patients, while adverse pregnancy outcomes and low-dose prednisone have no effect on offspring health. Key points ⢠Previous miscarriages and ANA positivity are risk factors for APOs in RA patients. ⢠Adverse pregnancy outcomes and low-dose prednisone during pregnancy have no effect on offspring health.
Asunto(s)
Aborto Espontáneo , Artritis Reumatoide , Complicaciones del Embarazo , Aborto Espontáneo/epidemiología , Adolescente , Anticuerpos Antinucleares , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Prednisona/uso terapéutico , Embarazo , Complicaciones del Embarazo/etiología , Resultado del Embarazo/epidemiología , Factores de RiesgoRESUMEN
To screen, prepare, identify, and evaluate the activities of natural antioxidants for treating chronic diseases caused by oxidative stress. Two algal proteins, namely ZD10 and ZD60, precipitated with 10 and 60% (NH4)2SO4 were extracted from red algae Eucheuma cottonii (E. cottonii) and hydrolyzed using five proteolytic enzymes. The results showed that ZD60 played the most significant role in the enhancement of 2,2-diphenyl-1-picrylhydrazyl radical (DPPHâ ) scavenging activity (25.91 ± 0.24%) among all protein hydrolysates. Subsequently, six antioxidant peptides (EP1-EP6) were isolated from the papain hydrolysate of ZD60 by ultrafiltration and chromatography methods. Their amino acid sequences were identified as Thr-Ala (EP1), Met-Asn (EP2), Tyr-Ser-Lys-Thr (EP3), Tyr-Ala-Val-Thr (EP4), Tyr-Leu-Leu (EP5), and Phe-Tyr-Lys-Ala (EP6) with molecular weights of 190.21, 263.33, 497.55, 452.51, 407.51, and 527.62 Da, respectively. Of which, EP3, EP4, EP5, and EP6 showed strong scavenging activities on DPPHâ , hydroxyl radical (HOâ ), and superoxide anion radical (O- 2â ). Moreover, EP4 and EP5 could significantly protect human umbilical vein endothelial cells (HUVECs) from H2O2-induced oxidative damage by increasing the levels of antioxidant enzyme systems including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) to reduce the levels of reactive oxygen species (ROS) (60.51 and 51.74% of model group) and malondialdehyde (MDA) (75.36 and 64.45% of model group). In addition, EP4 and EP5 could effectively inhibit H2O2-induced apoptosis by preventing HUVECs from early apoptosis to late apoptosis. These results indicated that the antioxidant peptides derived from E. cottonii, especially EP4 and EP5, could serve as the natural antioxidants applied in pharmaceutical products to treat chronic cardiovascular diseases caused by oxidative damage, such as coronary heart disease, atherosclerosis, etc.