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As northern latitudes experience rapid winter warming, there is an urgent need to assess the effect of varying winter conditions on tree growth and forest carbon sequestration potential. We examined tree growth responses to variability in cold-season (NovemberApril) frequency of freeze days (FFD) over 1951 to 2018 using tree-ring data from 35,217 trees and 57 species at 4,375 sites distributed across Canada. We found that annual radial growth responses to FFD varied by species, with some commonalities across genera and clades. The growth of gymnosperms with late spring leaf-out strategies was negatively related to FFD; years with high FFD were most detrimental to the annual growth of Pinus banksiana, Pinus contorta, Larix lyalli, Abies amabilis, and Abies lasiocarpa. In contrast, the growth of angiosperms with early leaf-out strategies, namely, Populus tremuloides and Betula papyrifera, was better in the coldest years, and gymnosperms with intermediate leaf-out timing, such as widespread Picea mariana and Picea glauca, had no consistent relationship to FFD. Tree growth responses to FFD were further modulated by tree size, tree age, regional climate (i.e., mean cold-season temperature), and local site conditions. Overall, our results suggest that moderately warming winters may temporarily improve the growth of widespread pines and some high-elevation conifers in western Canada, whereas warming winters may be detrimental to the growth of widespread boreal angiosperms. Our findings also highlight the value of using species-specific climate-growth relationships to refine predictions of forest carbon dynamics.
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Bosques , Árboles , Secuestro de Carbono , Cambio Climático , Estaciones del AñoRESUMEN
INTRODUCTION: Triple-negative breast cancer (TNBC) is known for its aggressive behaviors and lacking of effective treatment. Programmed cell death ligand-1 (PD-L1) inhibitor has just been approved for using in the management of advanced TNBC. To accurately screen TNBC sensitive to anti-PD-L1 treatment and to explore the feasibility of the ataxia-telangiectasia mutation protein (ATM) inhibitor combined with PD-L1 inhibitor, radiotherapy and chemotherapy, we focus on whether ATM participates in the regulation of PD-L1 and affects the prognosis of patients through c-Src, signal transducer and activator of transcription 1&3 (STAT1 and STAT3). MATERIALS AND METHODS: We used immunohistochemical staining to explore the relationship of ATM with c-Src, STAT1, STAT3, PD-1/PD-L1, Tumor-infiltrating lymphocytes (TILs), as well as other clinicopathologic features in 86 pathological stage III TNBCs. Their impact on prognosis was also explored. RESULTS: We found ATM expression was negatively correlated with STAT1, STAT3, PD-L1, TILs and CD8 + cells in TNBC. STAT1 positively correlated the expression of PD-L1. In TNBC with ATM low expression, STAT3 was an independent factor for improved prognosis, while PD-L1 was an independent negative prognostic factor. Furthermore, in low ATM group, the phosphorylation of tyrosine at position 419 of c-Src (p-c-src Y419) was correlated with the overexpression of STAT3. CONCLUSION: Locally advanced TNBC with low ATM expression may be more likely to benefit from anti-PD-L1 inhibitors. The feasibility of ATM functional inhibitor combined with immune checkpoint blockade therapies in the treatment of TNBC is also worthy of further exploration. Our study suggests that STAT3 has different impacts on tumor progression in different tumors.
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Neoplasias de la Mama Triple Negativas , Proteínas de la Ataxia Telangiectasia Mutada/genética , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/metabolismo , Humanos , Inhibidores de Puntos de Control Inmunológico , Ligandos , Linfocitos Infiltrantes de Tumor , Mutación , Pronóstico , Receptor de Muerte Celular Programada 1/metabolismo , Factor de Transcripción STAT1/genética , Factor de Transcripción STAT1/metabolismo , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/terapia , Tirosina/metabolismoRESUMEN
INTRODUCTION: Triple negative breast cancer (TNBC) is an aggressive cancer subtype and lack of effective targeted therapies. It has been recently reported that Interleukin 17 (IL-17), a family of cytokines secreted in tumor microenvironment, affects tumor progression through a variety of molecular pathways. Its role in TNBC is so far still poorly explored. MATERIALS AND METHODS: We employed immunohistochemistry to evaluate the distribution of IL-17+ cells in TNBC with no special type features (TNBC-NST), their association with tumor microangiogenesis, as well as their impact on prognosis of the patients. RESULTS: In comparison to medullary carcinoma with triple-negative molecular features (TNBC-MC), we found a significant increase in IL-17+ cell infiltrates in intratumoral stroma and extratumoral stroma of TNBC-NST. Similarly, stromal cells with co-expression of CD4 and IL-17 were noted in intratumoral and extratumoral stroma in both TNBC-NST and TNBC-MC. In addition, intratumoral IL-17+ cells were positively associated with tumor cell expression of vascular endothelial growth factor A (VEGFA) and with intratumoral tumor microvascular density (MVD). Multivariate analysis identified that intratumoral IL-17+ cells (P = 0.018), MVD (P = 0.039), and TNM stage (P = 0.002) were independent prognostic factors for predicting poor PFS. CONCLUSION: The study indicates that IL-17 is overexpressed in intratumoral stromal cells of TNBC-NST. The overexpression of IL-17 might engage in active tumor microangiogenesis through its signal transduction pathways resulting in increased tumor secretion of VEGFA, and then promote tumor progression. IL-17 might serve as a potential new target for individualized therapy to TNBC-NST patients by development of specific antibodies. Additional study is deemed to further explore the role of IL-17+ stromal cells in breast cancer.
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Biomarcadores de Tumor/metabolismo , Interleucina-17/metabolismo , Neovascularización Patológica , Células del Estroma/inmunología , Neoplasias de la Mama Triple Negativas/patología , Microambiente Tumoral/inmunología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Femenino , Humanos , Pronóstico , Transducción de Señal , Células del Estroma/metabolismo , Células del Estroma/patología , Tasa de Supervivencia , Neoplasias de la Mama Triple Negativas/inmunología , Neoplasias de la Mama Triple Negativas/metabolismoRESUMEN
Considerable evidence exists that current global temperatures are higher than at any time during the past millennium. However, the long-term impacts of rising temperatures and associated shifts in the hydrological cycle on the productivity of ecosystems remain poorly understood for mid to high northern latitudes. Here, we quantify species-specific spatiotemporal variability in terrestrial aboveground biomass stem growth across Canada's boreal forests from 1950 to the present. We use 873 newly developed tree-ring chronologies from Canada's National Forest Inventory, representing an unprecedented degree of sampling standardization for a large-scale dendrochronological study. We find significant regional- and species-related trends in growth, but the positive and negative trends compensate each other to yield no strong overall trend in forest growth when averaged across the Canadian boreal forest. The spatial patterns of growth trends identified in our analysis were to some extent coherent with trends estimated by remote sensing, but there are wide areas where remote-sensing information did not match the forest growth trends. Quantifications of tree growth variability as a function of climate factors and atmospheric CO2 concentration reveal strong negative temperature and positive moisture controls on spatial patterns of tree growth rates, emphasizing the ecological sensitivity to regime shifts in the hydrological cycle. An enhanced dependence of forest growth on soil moisture during the late-20th century coincides with a rapid rise in summer temperatures and occurs despite potential compensating effects from increased atmospheric CO2 concentration.
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Dióxido de Carbono/química , Cambio Climático , Bosques , Árboles/crecimiento & desarrollo , Biomasa , Canadá , Ciclo del Carbono , Ecología , Geografía , Modelos Estadísticos , Análisis de Regresión , Taiga , Temperatura , Factores de TiempoRESUMEN
Dual-probe fluorescence in situ hybridization (D-FISH) is a widely accepted method to determine the gene amplification status of human epidermal growth factor receptor 2 (Her-2). In 2013, the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) updated the guidelines on the Her-2 testing for invasive breast cancer (BCa). The interpretation criteria for D-FISH changed accordingly. In this study, we compared the Her-2 FISH statuses based on the 2013 and 2007 ASCO/CAP guidelines in 1931 cases of BCa with Her-2 D-FISH testing at our hospital. We analyzed the clinicopathologic features of cases with equivocal results by the 2013 ASCO/CAP guidelines. Although the guideline update significantly improved the detection rate of Her-2 amplification, it also significantly increased the rate of equivocal results, posing a dilemma for clinical management. The equivocal results had a good reproducibility. The distribution of D-FISH-equivocal cases did not correlate with Her-2 status by immunohistochemistry, suggesting that Her-2 D-FISH equivocality may not reflect Her-2 overexpression. Compared with Her-2-negative cases by D-FISH, Her-2 D-FISH-equivocal cases had higher Ki67 expression, higher histological grade, more frequent lymph node metastasis, and lower estrogen receptor α expression, indicating a group of BCa with worse prognosis. The clinical significance of Her-2-equivocal results by D-FISH warrants further investigation.
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Neoplasias de la Mama/diagnóstico , Amplificación de Genes , Receptor ErbB-2/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Centrómero/genética , Cromosomas Humanos Par 17/genética , Femenino , Humanos , Hibridación Fluorescente in Situ , Guías de Práctica Clínica como Asunto , Receptor ErbB-2/metabolismo , Sensibilidad y EspecificidadRESUMEN
An increasing number of studies conclude that water limitations and heat stress may hinder the capacity of black spruce (Picea mariana (Mill.) B.S.P.) trees, a dominant species of Canada's boreal forests, to grow and assimilate atmospheric carbon. However, there is currently no scientific consensus on the future of these forests over the next century in the context of widespread climate warming. The large spatial extent of black spruce forests across the Canadian boreal forest and associated variability in climate, demography, and site conditions pose challenges for projecting future climate change responses. Here we provide an evaluation of the impacts of climate warming and drying, as well as increasing [CO2 ], on the aboveground productivity of black spruce forests across Canada south of 60°N for the period 1971 to 2100. We use a new extensive network of tree-ring data obtained from Canada's National Forest Inventory, spatially explicit simulations of net primary productivity (NPP) and its drivers, and multivariate statistical modeling. We found that soil water availability is a significant driver of black spruce interannual variability in productivity across broad areas of the western to eastern Canadian boreal forest. Interannual variability in productivity was also found to be driven by autotrophic respiration in the warmest regions. In most regions, the impacts of soil water availability and respiration on interannual variability in productivity occurred during the phase of carbohydrate accumulation the year preceding tree-ring formation. Results from projections suggest an increase in the importance of soil water availability and respiration as limiting factors on NPP over the next century due to warming, but this response may vary to the extent that other factors such as carbon dioxide fertilization, and respiration acclimation to high temperature, contribute to dampening these limitations.
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Cambio Climático , Modelos Teóricos , Picea/crecimiento & desarrollo , Canadá , Dióxido de Carbono , Clima , Suelo/química , Taiga , Temperatura , Agua/análisisRESUMEN
PURPOSE: Statistical shrinkage is a potential statistical method to improve the accuracy of signal detection results and avoid spurious associations detected by disproportionality analyses. In this study, we introduced statistical shrinkage influence on disproportionality methods in spontaneous reporting system in China. METHODS: We added the shrinkage parameters in the numerator and denominator, denoted as in the formula of disproportionality analysis. The shrinkage parameters were subjectively set to between 0 and 5, with an interval of 0.1. Adverse drug reaction product label database was deemed as a proxy of golden standard to evaluate the effect of statistical shrinkage. Reports in the years of 2010-2011 were extracted from the national spontaneous reporting system database as the data source for analysis in this study. RESULTS: When α was around 0.5, the Youden index reached the maximum for each disproportionality methods in this study. The value of 0.6 was suggested as the most appropriate statistical shrinkage parameter for reporting odds ratio and proportional reporting ratio and 0.2 for information component based on the spontaneous reporting system of China.
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Sistemas de Registro de Reacción Adversa a Medicamentos/estadística & datos numéricos , Bases de Datos Factuales/estadística & datos numéricos , Farmacovigilancia , Algoritmos , China/epidemiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Humanos , Oportunidad RelativaRESUMEN
BACKGROUND: The prozone phenomenon is known to be associated with high antibody titers; other associations, such as host factors, have not been elucidated. METHODS: A retrospective analysis was conducted to evaluate the incidence of the prozone phenomenon of the syphilis rapid plasma reagin (RPR) test among 46 856 clinical samples, between June 2010 and June 2013. Logistic regression was used to analyze the risk factors of the prozone phenomenon. RESULTS: Our results showed that the incidence of the prozone phenomenon was low (0.83%) and could occur during any clinical phase, particularly during primary and secondary syphilis. Pregnancy and neurosyphilis were associated with the prozone phenomenon; sex, age, and whether the patient had been treated were not. The results also revealed that the prozone phenomenon not only occurred in patients with a high titer but also could occur in patients with a moderate/low titer. In fact, almost 31% of the patients with the prozone phenomenon had titers ≤1:16. CONCLUSIONS: The prozone phenomenon in the RPR test was associated with the phase of syphilis, pregnancy, and neurosyphilis as well as a range of RPR titers between 1:8 and 1:512. This latter finding is in contrast to previous reports that the prozone phenomenon is associated with very high RPR titers.
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Reaginas/sangre , Sífilis/diagnóstico , Adolescente , Adulto , Anciano , Pruebas de Aglutinación , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Incidencia , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Embarazo , Estudios Retrospectivos , Factores de Riesgo , Serodiagnóstico de la Sífilis , Adulto JovenRESUMEN
BACKGROUND: Algorithms for the diagnosis of syphilis continue to be a source of great controversy, and numerous test interpretations have perplexed many clinicians. METHODS: We conducted a cross-sectional study of 24 124 subjects to analyze 3 syphilis testing algorithms: traditional algorithm, reverse algorithm, and the European Centre for Disease Prevention and Control (ECDC) algorithm. Every serum sample was simultaneously evaluated using the rapid plasma reagin, Treponema pallidum particle agglutination, and chemiluminescence immunoassay tests. With the results of clinical diagnoses of syphilis as a gold standard, we evaluated the diagnostic accuracy of the 3 syphilis testing algorithms. The κ coefficient was used to compare the concordance between the reverse algorithm and the ECDC algorithm. RESULTS: Overall, 2749 patients in our cohort were diagnosed with syphilis. The traditional algorithm had the highest negative likelihood ratio (0.24), a missed diagnosis rate of 24.2%, and only 75.81% sensitivity. However, both the reverse and ECDC algorithms had higher diagnostic efficacy than the traditional algorithm. Their sensitivity, specificity, and accuracy were 99.38%-99.85%, 99.98%-100.00%, and 99.93%-99.96%, respectively. Moreover, the overall percentage of agreement and κ value between the reverse and the ECDC algorithms were 99.9% and 0.996, respectively. CONCLUSIONS: Our research supported use of the ECDC algorithm, in which syphilis screening begins with a treponemal immunoassay that is followed by a second, different treponemal assay as a confirmatory test in high-prevalence populations. In addition, our results indicated that nontreponemal assay is unnecessary for syphilis diagnosis but can be recommended for determining serological activity and the effect of syphilis treatment.
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Serodiagnóstico de la Sífilis/métodos , Treponema pallidum/inmunología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Niño , Preescolar , Estudios Transversales , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Suero/inmunología , Adulto JovenRESUMEN
The 20th century was a pivotal period at high northern latitudes as it marked the onset of rapid climatic warming brought on by major anthropogenic changes in global atmospheric composition. In parallel, Arctic sea ice extent has been decreasing over the period of available satellite data records. Here, we document how these changes influenced vegetation productivity in adjacent eastern boreal North America. To do this, we used normalized difference vegetation index (NDVI) data, model simulations of net primary productivity (NPP) and tree-ring width measurements covering the last 300 years. Climatic and proxy-climatic data sets were used to explore the relationships between vegetation productivity and Arctic sea ice concentration and extent, and temperatures. Results indicate that an unusually large number of black spruce (Picea mariana) trees entered into a period of growth decline during the late-20th century (62% of sampled trees; n = 724 cross sections of age >70 years). This finding is coherent with evidence encoded in NDVI and simulated NPP data. Analyses of climatic and vegetation productivity relationships indicate that the influence of recent climatic changes in the studied forests has been via the enhanced moisture stress (i.e. greater water demands) and autotrophic respiration amplified by the declining sea ice concentration in Hudson Bay and Hudson Strait. The recent decline strongly contrasts with other growth reduction events that occurred during the 19th century, which were associated with cooling and high sea ice severity. The recent decline of vegetation productivity is the first one to occur under circumstances related to excess heat in a 300-year period, and further culminates with an intensifying wildfire regime in the region. Our results concur with observations from other forest ecosystems about intensifying temperature-driven drought stress and tree mortality with ongoing climatic changes.
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Cambio Climático , Cubierta de Hielo , Picea/crecimiento & desarrollo , Árboles/crecimiento & desarrollo , América del NorteRESUMEN
This study characterizes psychiatric manifestations as a primary symptom of neurosyphilis (NS). Fifty-two of the 169 NS patients presented with psychiatric manifestations, many patients had characteristics of more than one syndrome, including cognitive impairment, personality disorders, delirium, hostility, dysarthria, confusion, disruption of their sleep-wake cycle, fecal and urinary incontinence, dysphoria, paranoia, hallucinations, expansive mood, and mania. Fifty-two patients had positive sera RPR and T. pallidum particle agglutination (TPPA), 75% had positive CSF RPR, 96.2% had positive CSF TPPA, 44.2% had CSF pleocytosis and elevated CSF proteins, and 70.0% had nonspecific, abnormal brain MRIs. These results indicate that NS mimics almost all psychiatric disorders.
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Trastornos del Conocimiento/etiología , Trastornos Mentales/etiología , Neurosífilis/complicaciones , Trastornos de la Personalidad/etiología , Adulto , Anciano , Aglutinación , Femenino , Globo Pálido/patología , Globo Pálido/virología , Humanos , Recuento de Leucocitos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neurosífilis/líquido cefalorraquídeo , Estudios RetrospectivosRESUMEN
BACKGROUND: Dermatomyositis (DM)/polymyositis (PM) is a systemic autoimmune disease characterized by proximal limb muscle with high morbidity and mortality and poor prognosis mediated by immune dysfunction; its etiology is unknown. DM/PM patients are at excessive risk of interstitial lung disease (ILD) and a higher risk of death. However, the role of circulating lymphocyte subsets, which play a pivotal role in occurrence and progression of DM/PM and ILD, respectively, remains unclear in DM/PM patients with ILD. METHODS: Demographic characteristics, general data, and peripheral lymphocyte levels measured by flow cytometry were collected and analyzed in 47 DM/PM patients with ILD, 65 patients without ILD, and 105 healthy controls (HCs). RESULTS: The most important first symptom of DM/PM patients is rash. Compared with non-ILD patients, the levels of neutrophil/lymphocyte ratio (NLR), systemic inflammatory response index (SIRI) were significantly higher and the levels of C reactive protein (CRP) were significantly lower in patients with ILD. Compared with HCs, DM/PM patients, with or without ILD, had decreased absolute counts of T, CD4 + T, CD8 + T, natural killer (NK), helper T (Th) 1, Th2, Th17, and regulatory T (Treg)cells. The fewest Th1 and Treg cells and the the lowest CD8 + T and Th1 cells percentages were seen in peripheral blood of patients with ILD. Longer duration, decreased lymphocyte/monocyte ratio (LMR)levels and CD8 + T and Th1 cells proportions, and fewer circulating Treg cells were independent risk factors for DM/PM with ILD. CONCLUSIONS: The identification of peripheral blood T lymphocyte subsets, especially Treg cells, and blood count in DM/PM appears to be useful in the comprehensive assessment of clinical lung involvement.
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Dermatomiositis , Enfermedades Pulmonares Intersticiales , Polimiositis , Humanos , Dermatomiositis/complicaciones , Estudios Retrospectivos , Polimiositis/complicaciones , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/diagnóstico , Biomarcadores , PronósticoRESUMEN
Interleukin-6 (IL-6) is a pleiotropic cytokine and exerts its complex biological functions mainly through three different signal modes, called cis-, trans-, and cluster signaling. When IL-6 binds to its membrane or soluble receptors, the co-receptor gp130 is activated to initiate downstream signaling and induce the expression of target genes. In the liver, IL-6 can perform its anti-inflammatory activities to promote hepatocyte reprogramming and liver regeneration. On the contrary, IL-6 also exerts the pro-inflammatory functions to induce liver aging, fibrosis, steatosis, and carcinogenesis. However, understanding the roles and underlying mechanisms of IL-6 in liver physiological and pathological processes is still an ongoing process. So far, therapeutic agents against IL6, IL6 receptor (IL6R), IL-6-sIL-6R complex, or IL-6 downstream signal transducers have been developed, and determined to be effective in the intervention of inflammatory diseases and cancers. In this review, we summarized and highlighted the understanding of the double-edged effects of IL-6 in liver homeostasis, aging, inflammation, and chronic diseases, for better shifting the "negative" functions of IL-6 to the "beneficial" actions, and further discussed the potential therapeutic effects of targeting IL-6 signaling in the clinics.
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Histopathological tissue classification is a fundamental task in computational pathology. Deep learning (DL)-based models have achieved superior performance but centralized training suffers from the privacy leakage problem. Federated learning (FL) can safeguard privacy by keeping training samples locally, while existing FL-based frameworks require a large number of well-annotated training samples and numerous rounds of communication which hinder their viability in real-world clinical scenarios. In this article, we propose a lightweight and universal FL framework, named federated deep-broad learning (FedDBL), to achieve superior classification performance with limited training samples and only one-round communication. By simply integrating a pretrained DL feature extractor, a fast and lightweight broad learning inference system with a classical federated aggregation approach, FedDBL can dramatically reduce data dependency and improve communication efficiency. Five-fold cross-validation demonstrates that FedDBL greatly outperforms the competitors with only one-round communication and limited training samples, while it even achieves comparable performance with the ones under multiple-round communications. Furthermore, due to the lightweight design and one-round communication, FedDBL reduces the communication burden from 4.6 GB to only 138.4 KB per client using the ResNet-50 backbone at 50-round training. Extensive experiments also show the scalability of FedDBL on model generalization to the unseen dataset, various client numbers, model personalization and other image modalities. Since no data or deep model sharing across different clients, the privacy issue is well-solved and the model security is guaranteed with no model inversion attack risk. Code is available at https://github.com/tianpeng-deng/FedDBL.
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Montmorillonite (MMT) is known as an ion-exchangeable material, and cations between MMT nanosheets are easily exchanged by other cations. In this work, Ca2+, Fe3+, and Al3+ intercalated two-dimensional MMT membranes were developed by ion exchange of pristine MMT membranes (Na+-MMT), and their ion and dye removal abilities were investigated. The d-spacings of hydrated Fe3+ intercalated MMT membrane (Fe3+-MMT) and Al3+ intercalated MMT membrane (Al3+-MMT) were decreased compared with hydrated Na+-MMT membrane due to the stronger electrostatic attraction between Fe3+/Al3+ and negatively charged MMT nanosheets. Ion and dye sieving performances were improved significantly after the intercalation of Ca2+, Fe3+, and Al3+ into MMT membranes. Al3+-MMT membrane with a thickness of 1.17 µm could exclude 94% of Na+, and its ion sieving performance remained stable during a 120-h ion sieving experiment. Moreover, the rejection rate for rhodamine B (RB) reached 94% using an Al3+-MMT membrane with a thickness of 500 nm, and a water permeance of 73 L m-2 h-1 bar-1 was achieved. The excellent ion and dye sieving performances make it promising in the application of desalination and nanofiltration.
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Iatrogenic aortic dissection is a rare but life-threatening complication of coronary artery bypass surgery. We report a case with incidentally detected iatrogenic aortic dissection related to aorta cross-clamping that was successfully managed with watchful follow-up. The decision making was based on 3-dimensional holographic and fluid dynamic analysis guidance.
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Disección Aórtica , Puente de Arteria Coronaria , Holografía , Enfermedad Iatrogénica , Imagenología Tridimensional , Humanos , Disección Aórtica/etiología , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/cirugía , Holografía/métodos , Puente de Arteria Coronaria/efectos adversos , Masculino , Tomografía Computarizada por Rayos X , Anciano , Hidrodinámica , Aneurisma de la Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/diagnóstico , FemeninoRESUMEN
BACKGROUND: Neurosyphilis (NS) may present with neuropsychiatric disorders characterized by cognitive impairment, personality disorders, and confusion, among others. Very few studies have focused on neuropsychiatric disorders secondary to NS in elderly people. METHOD: A retrospective chart review was performed to characterize the psychiatric findings, clinical signs and symptoms, laboratory findings, and brain magnetic resonance imaging results of ten elderly inpatients with NS. RESULTS: In these ten patients, the most common presenting symptoms included a wide variety of psychiatric manifestations. The serum rapid plasma regain (RPR) and Treponema pallidum particle agglutination assay (TPPA) of the ten patients were positive, with positive CSF TPPA and RPR rates of 100% and 60%, respectively. In addition, 90% of the patients demonstrated abnormal imaging, including cerebral atrophy, infarct ischemic stroke, and hydrocephalus. CONCLUSIONS: Our findings support the importance of serological tests for syphilis as a routine component of the evaluation of patients with clinically evident neurological or psychiatric symptoms. If the serology is positive, all of the patients should be examined with a lumbar puncture. Moreover, psychiatric illnesses secondary to NS in the elderly also deserve medical attention.
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Trastornos Mentales/complicaciones , Trastornos Mentales/diagnóstico , Neurosífilis/complicaciones , Neurosífilis/diagnóstico , Serodiagnóstico de la Sífilis/métodos , Treponema pallidum/aislamiento & purificación , Anciano , Pruebas de Aglutinación/métodos , China , Trastornos del Conocimiento/fisiopatología , Electroencefalografía , Ensayo de Inmunoadsorción Enzimática , Femenino , Seronegatividad para VIH , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Trastornos Mentales/psicología , Neurosífilis/psicología , Reaginas/sangre , Estudios Retrospectivos , Pruebas Serológicas/métodos , Punción Espinal , Treponema pallidum/inmunologíaRESUMEN
PURPOSE: To evaluate the clinical effect of complete denture restoration in edentulous patients using secondary functional impression. METHODS: Complete denture restoration was performed in 433 edentulous patients using secondary functional impression. The Geriatric Oral Health Assessment Index (GOHAI) was used to evaluate patients' oral health-related quality of life before and after restoration. All patients were divided into 3 groups according to whether they had a history of denture restoration: no denture group(ND)ï¼removable partial denture group(RPD), complete denture group(CD). In CD group, 30 patients were asked to chew two-colour gum. The SDhue value was evaluated by using ViewGum software. SPSS 26.0 software package was used for data analysis. RESULTS: The oral health-related quality of life was improved in all the 3 groups after restoration, and the GOHAI index 1 month after restoration was significantly higher than that before restoration(Pï¼0.05). In CD group, SDHue value of 30 patients after restoration was significantly lower than that before restoration(Pï¼0.05). CONCLUSIONS: Secondary functional impression is simple and fast, and can improve the satisfaction of patients after complete denture restoration.
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Boca Edéntula , Salud Bucal , Humanos , Anciano , Calidad de Vida , Dentadura Completa , Masticación , Satisfacción del PacienteRESUMEN
Overexpression or gene mutation of SHP2 is closely linked with a variety of cancers and has been identified as a crucial anticancer target. In the study, we took SHP2 allosteric inhibitor SHP099 as the lead compound, and 32 1,3,4-thiadiazole derivatives were identified as selective allosteric inhibitors of SHP2. In vitro enzyme activity test showed that some compounds had high inhibition on full length SHP2, and almost no activity on homologous protein SHP1, exhibiting high selectivity. Compound YF704 (4w) had the best inhibition activity, with IC50 value of 0.25 ± 0.02 µM, and also showed strong inhibitory activity on SHP2-E76K and SHP2-E76A, with IC50 values of 6.88 ± 0.69 µM and 1.38 ± 0.12 µM, respectively. CCK8 proliferation test found that multiple compounds would effectively inhibit the proliferation of a variety of cancer cells. Among them, the IC50 values of compound YF704 on MV4-11 and NCI-H358 cells were 3.85 ± 0.34 µM and 12.01 ± 0.62 µM, respectively. Specially, these compounds were sensitive to NCI-H358 cells containing KRASG12C mutation, thus overcoming the problem that SHP099 was insensitive to such cells. Apoptosis experiment showed that compound YF704 would effectively induce apoptosis of MV4-11 cells. Western blot showed that compound YF704 would downregulate the phosphorylation levels of Erk1/2 and Akt in MV4-11 and NCI-H358 cells. Molecular docking study show that compound YF704 would effectively bind to the allosteric region of SHP2 and form hydrogen bond interactions with key residues Thr108, Arg111 and Phe113. Molecular dynamics study further revealed the binding mechanism of SHP2 and compound YF704. In conclusion, we hope to provide potential SHP2 selective inhibitors and provide valuable clues for cancer treatment.
Asunto(s)
Neoplasias , Tiadiazoles , Humanos , Simulación de Dinámica Molecular , Simulación del Acoplamiento Molecular , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Tiadiazoles/farmacología , Proteína Tirosina Fosfatasa no Receptora Tipo 11 , Inhibidores Enzimáticos/farmacologíaRESUMEN
Long-term overfertilization increases soil salinity and disease occurrence and reduces crop yield. Integrated application of microbial agents with low fertigation input might be a sustainable and cost-effective strategy. Herein, the promoting effects of Bacillus velezensis B006 on the growth of Chinese cabbage under different fertigation conditions in field trials were studied and the underlying mechanisms were revealed. In comparison with normal fertigation (water potential of -30 kPa and soluble N, P, K of 29.75, 8.26, 21.48 Kg hm-2) without B006 application, the combination of B. velezensis B006 and reduced fertigation input (-50 kPa and N, P, K of 11.75, 3.26, 6.48 Kg hm-2) promoted cabbage growth and root development, restrained the occurrence of soft rot disease, and improved the yield. High-performance liquid chromatography (HPLC) analyses indicated that B006 application promoted the production of indole-3-acetic acid and salicylic acid in cabbage roots, which are closely related to plant growth. Rhizosphere microbiota analyses indicated that the combination of low fertigation input and B006 application promoted the enrichment of Streptomyces, Lechevalieria, Promicromonospora, and Aeromicrobium and the abundance of Lechevalieria was positively correlated with the root length and vitality. This suggested that the integrated application of reduced fertigation and Bacillus is highly efficient to improve soil ecology and productivity and will benefit the sustainable development of crop cultivation in a cost-effective way.