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Undifferentiated round cell sarcomas (URCS) represent a diverse group of tumors, including conventional Ewing sarcoma, round cell sarcoma with EWSR1/FUS-non-ETS fusions, CIC-rearranged sarcoma, and sarcoma with BCOR alterations. Since 2018, 3 cases of URCS with a novel CRTC1::SS18 gene fusion have been reported in the literature. Herein, we report 3 additional cases of CRTC1::SS18 sarcoma, thereby doubling the number of described cases and expanding the clinicopathologic features of this rare translocation sarcoma. Together with the previously reported cases, we show that the male-to-female ratio is 1:2 with a median age of 34 years (range, 12-42 years). Tumors occurred primarily in intramuscular locations involving the lower extremity. Histologically, all tumors contained uniform round-to-epithelioid cells with a moderate amount of eosinophilic cytoplasm growing in sheets and nests with prominent desmoplastic stroma reminiscent of desmoplastic small round cell tumor. Immunohistochemical results were nonspecific, demonstrating variable expression of CD99 (patchy), ALK, GATA3, and cyclin D1. RNA sequencing revealed CRTC1::SS18 gene fusions in all cases, involving exons 1 to 2 of CRTC1 (the 5' partner gene) on chromosome 19 and either exon 2 or exon 4 of SS18 (the 3' partner gene) on chromosome 18. The clinical course was variable. Although 1 previously reported case demonstrated aggressive behavior with a fatal outcome, 2 others had a relatively indolent course with gradual growth for 6 to 7 years prior to resection. Two cases developed metastatic disease, including 1 case with bilateral lung metastasis and 1 with locoregional spread to a lymph node. By analyzing the clinicopathologic features, we aimed to improve recognition of this rare translocation sarcoma to better understand its biologic potential, optimize patient management, and expand the current classification of URCS.
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This paper addresses the influence of time-varying delay and nonlinear activation functions with sector restrictions on the stability of discrete-time neural networks. Compared to previous works that mainly focuses on the influence of delay information, this paper devotes to activation nonlinear functions information to help compensate the analysis technique based on Lyapunov-Krasovskii functional (LKF). A class of delay-dependent Lurie-Postnikov type integral terms involving sector constraints of nonlinear activation function is proposed to complement the LKF construction. The less conservative criteria for the stability analysis of discrete-time delayed networks is given by using improved LKF. Numerical examples show that conservatism can be reduced by the delay-dependent integral terms involving nonlinear activation functions.
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Algoritmos , Redes Neurais de Computação , Fatores de TempoRESUMO
Exosomes, carrying distinctive biomolecules reflective of their parent cell's status and origin, show promise as liquid biopsy biomarkers for cancer diagnosis. However, their clinical translation remains challenging due to their relatively low concentration in body fluids. Surface-Enhanced Raman spectroscopy (SERS) has recently gained significant attention as a label-free and sensitive technique for exosome analysis. This review explores label-free SERS for exosome detection, covering exosome isolation and characterization methods, advancements in SERS substrates, and fingerprint analysis techniques using machine learning. Furthermore, we emphasize the challenges and offer insights into the future prospects of SERS-based exosome analysis to enhance cancer diagnosis.
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Exossomos , Neoplasias , Humanos , Exossomos/química , Análise Espectral Raman/métodos , Biomarcadores/análise , Biópsia Líquida/métodos , Neoplasias/diagnósticoRESUMO
For the flexible riser systems modeled with partial differential equations (PDEs), this article explores the boundary control problem in depth for the first time using a dynamic event-triggered mechanism (DETM). Given the intrinsic time-space coupling characteristic inherent in PDE computations, implementing a state-dependent DETM for PDE-based flexible risers presents a significant challenge. To overcome this difficulty, a novel dynamic event-triggered control method is introduced for flexible riser systems, focusing on optimizing available control inputs. In order to save computational costs from the controller to the actuator, a dynamic event-triggered adaptive boundary controller is designed to effectively reduce boundary position vibrations. Additionally, considering external disturbances, an adaptive bounded compensation term is incorporated to counteract the influence of external disturbances on the system. Addressing boundary position constraints, a new integral barrier Lyapunov function (iBLF) tailored specifically for flexible riser systems is introduced, thereby alleviating conservatism in the controller design of flexible risers modeled by PDEs. At last, the validity of the proposed method is demonstrated through a simulation example.
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The WHO classifications of hematolymphoid malignancies have recognized several distinct entities within the large B cell lymphomas, including the more recently described high-grade B cell lymphoma with 11q aberration (HGBCL-11q). We utilized genomic array to assess for chromosome 11q abnormalities in a broad set of aggressive B cell lymphomas from 27 patients with a focus on younger adults. The findings suggest more frequent alterations of 11q in diffuse large B cell lymphoma (DLBCL)/HGBCL-GC BCL2-, in comparison to cases of Burkitt lymphoma (BL) or DLBCL-GC BCL2+, and confirm a low genomic complexity score of BL. Variability identified in patterns of 11q alterations suggests genomic array studies may afford value over FISH testing as we continue to understand HGBCL-11q as a distinct entity, and interrogate cases of DLBCL/HGBCL-GC BCL2-.
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Aberrações Cromossômicas , Cromossomos Humanos Par 11 , Centro Germinativo , Linfoma Difuso de Grandes Células B , Fenótipo , Proteínas Proto-Oncogênicas c-bcl-2 , Humanos , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Cromossomos Humanos Par 11/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Centro Germinativo/patologia , Adulto , Pessoa de Meia-Idade , Feminino , Masculino , Idoso , Adulto Jovem , Idoso de 80 Anos ou mais , Hibridização in Situ Fluorescente , AdolescenteRESUMO
Introduction: Heat-killed probiotics, as a type of inactivated beneficial microorganisms, possess an extended shelf life and broader adaptability compared to their live counterparts. This study aimed to investigate the impact of heat-killed Lactobacillus acidophilus (L. acidophilus, LA) - a deactivated probiotic on the growth performance, digestibility, antioxidant status, immunity and cecal microbiota of rabbits. Methods: Two hundred weaned Hyla rabbits were randomly allocated into five equal groups (CON, L200, L400, L600, and L800). Over a 28-day period, the rabbits were fed basal diets supplemented with 0, 200, 400, 600, and 800 mg/kg of heat-killed LA, respectively. Results: Results revealed a significant reduction in the feed-to-gain ratio (F/G) in the L600 and L800 groups (p < 0.05). Additionally, the L800 group exhibited significantly higher apparent digestibility of crude fiber (CF) and crude protein (CP) (p < 0.05). Regarding digestive enzyme activities, enhanced trypsin and fibrinase activities were observed in the L600 and L800 groups (p < 0.05). Concerning the regulation of the body's antioxidant status, the L800 group demonstrated elevated levels of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) in both serum and ileal tissue (p < 0.05). In terms of immune capacity modulation, serum tumor necrosis factor-α (TNF-α) levels were significantly lower in the L600 and L800 groups (p < 0.05), while immunoglobulin A (IgA) and immunoglobulin M (IgM) levels were higher (p < 0.05). Additionally, the L800 group exhibited a substantial increase in secretory immunoglobulin A (SIgA) levels in the intestinal mucosa (p < 0.05). In comparison to the CON group, the L800 group exhibited a significant increase in the relative abundance of Phascolarctobacterium and Alistipes in the cecum (p < 0.05). Phascolarctobacterium demonstrated a positive correlation with SIgA (p < 0.05), IgM (p < 0.01), and Glutathione peroxidase (GSH-Px) (p < 0.05), while displaying a negative correlation with TNF-α levels (p < 0.05). Concurrently, Alistipes exhibited positive correlations with IgA (p < 0.05), IgM (p < 0.05), SIgA (p < 0.01), GSH-Px (p < 0.05), SOD (p < 0.05), and T-AOC (p < 0.01), and a negative correlation with TNF-α (p < 0.05). Discussion: In conclusion, the dietary incorporation of 600 mg/kg and 800 mg/kg of heat-killed LA positively influenced the growth performance, nutrient digestibility, antioxidant status, immune capacity and cecal microbiota of rabbits. This highlights the potential benefits of utilizing heat-killed probiotics in animal nutrition.
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Introduction: Yeast peptides have garnered attention as valuable nutritional modifiers due to their potential health benefits. However, the precise mechanisms underlying their effects remain elusive. This study aims to explore the potential of yeast peptides, when added to diets, to mitigate lipopolysaccharide (LPS)-induced intestinal damage and microbiota alterations in rabbits. Methods: A total of 160 35-day-old Hyla line rabbits (0.96 ± 0.06 kg) were randomly assigned to 4 groups. These groups constituted a 2 × 2 factorial arrangement: basal diet (CON), 100 mg/kg yeast peptide diet (YP), LPS challenge + basal diet (LPS), LPS challenge +100 mg/kg yeast peptide diet (L-YP). The experiment spanned 35 days, encompassing a 7-day pre-feeding period and a 28-day formal trial. Results: The results indicated that yeast peptides mitigated the intestinal barrier damage induced by LPS, as evidenced by a significant reduction in serum Diamine oxidase and D-lactic acid levels in rabbits in the L-YP group compared to the LPS group (p < 0.05). Furthermore, in the jejunum, the L-YP group exhibited a significantly higher villus height compared to the LPS group (p < 0.05). In comparison to the LPS group, the L-YP rabbits significantly upregulated the expression of Claudin-1, Occludin-1 and ZO-1 in the jejunum (p < 0.05). Compared with the CON group, the YP group significantly reduced the levels of rabbit jejunal inflammatory cytokines (TNF-α, IL-1ß and IL-6) and decreased the relative mRNA expression of jejunal signaling pathway-associated inflammatory factors such as TLR4, MyD88, NF-κB and IL-1ß (p < 0.05). Additionally, notable changes in the hindgut also included the concentration of short-chain fatty acids (SCFA) of the YP group was significantly higher than that of the CON group (p < 0.05). 16S RNA sequencing revealed a substantial impact of yeast peptides on the composition of the cecal microbiota. Correlation analyses indicated potential associations of specific gut microbiota with jejunal inflammatory factors, tight junction proteins, and SCFA. Conclusion: In conclusion, yeast peptides have shown promise in mitigating LPS-induced intestinal barrier damage in rabbits through their anti-inflammatory effects, modulation of the gut microbiota, and maintenance of intestinal tight junctions.
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The calcified chondroid mesenchymal neoplasm (CCMN) represents a recently recognized tumor type with only 50 well-documented cases in the English-language literature. Herein we report an additional case of CCMN presenting as a large mass in the temporomandibular joint region of a 41-year-old female. A review of previously reported cases and the current case of CCMN shows the following features: 1) average age 52 years (range 14-87 years) and an approximately even sex distribution; 2) most frequently involved sites: distal extremities (including foot, hand, wrist, forearm) (n=41) and temporomandibular joint/temporal/parotid region (n=9); 3) multilobular soft tissue tumor with chondroid to cartilaginous matrix, often grungy or lace-like calcifications, and variable cytologic atypia; 4) frequently detected FN1 rearrangement (n=15), including FN1 fusion with FGFR2 (n=7) or other receptor tyrosine kinases; 5) 2 reported local recurrences (after incomplete excision); 6) no reports of malignant biologic behavior.
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Calcinose , Neoplasias , Adulto , Feminino , Humanos , Calcinose/patologia , Calcinose/diagnóstico por imagem , Calcinose/cirurgia , Diagnóstico Diferencial , Transtornos da Articulação Temporomandibular/patologia , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/cirurgia , Neoplasias/diagnóstico , Neoplasias/patologia , Neoplasias/terapiaRESUMO
BACKGROUND: We recently found that butyrate could ameliorate inflammation of alcoholic liver disease (ALD) in mice. However, the exact mechanism remains incompletely comprehended. Here, we examined the role of butyrate on ALD-associated inflammation through macrophage (Mψ) regulation and polarization using in vivo and in vitro experiments. METHODS: For in vivo experiments, C57BL/6J mice were fed modified Lieber-DeCarli liquid diets supplemented with or without ethanol and sodium butyrate (NaB). After 6 weeks of treatment, mice were euthanized and associated indicators were analyzed. For in vitro experiments, lipopolysaccharide (LPS)-induced inflammatory murine RAW264.7 cells were treated with NaB or miR-155 inhibitor/mimic to verify the anti-inflammatory effect and underlying mechanism. RESULTS: The administration of NaB alleviated pathological damage and associated inflammation, including LPS, tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1ß levels in ALD mice. NaB intervention restored the imbalance of macrophage polarization by inhibiting inducible nitric oxide synthase (iNOS) and elevating arginase-1 (Arg-1). Moreover, NaB reduced histone deacetylase-1 (HDAC1), nuclear factor kappa-B (NF-κB), NOD-like receptor thermal protein domain associated protein 3 (NLRP3), and miR-155 expression in ALD mice, but also increased peroxisome proliferator-activated receptor-γ (PPAR-γ). Thus, MiR-155 was identified as a strong regulator of ALD. To further penetrate the role of miR-155, LPS-stimulated RAW264.7 cells co-cultured with NaB were treated with the specific inhibitor or mimic. Intriguingly, miR-155 was capable of negatively regulated inflammation with NaB intervention by targeting SOCS1, SHIP1, and IRAK-M genes. CONCLUSION: Butyrate suppresses the inflammation in mice with ALD by regulating macrophage polarization via the HDAC1/miR-155 axis, which may potentially contribute to the novel therapeutic treatment for the disease.
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Hepatite Alcoólica , Hepatopatias Alcoólicas , MicroRNAs , Camundongos , Animais , Lipopolissacarídeos/farmacologia , Camundongos Endogâmicos C57BL , Hepatopatias Alcoólicas/patologia , Inflamação/metabolismo , Macrófagos , Ácido Butírico/farmacologia , Ácido Butírico/uso terapêutico , Ácido Butírico/metabolismo , NF-kappa B/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , MicroRNAs/metabolismoRESUMO
The PICALM::MLLT10 fusion is a rare but recurrent cytogenetic abnormality in acute leukemia, with limited clinicopathologic and outcome data available. Herein, we analyzed 156 acute leukemia patients with PICALM::MLLT10 fusion, including 12 patients from our institutions and 144 patients from the literature. The PICALM::MLLT10 fusion preferentially manifested in pediatric and young adult patients, with a median age of 24 years. T-lymphoblastic leukemia/lymphoma (T-ALL) constituted 65% of cases, acute myeloid leukemia (AML) 27%, and acute leukemia of ambiguous lineage (ALAL) 8%. About half of T-ALL were classified as an early T-precursor (ETP)-ALL. In our institutions' cohort, mediastinum was the most common extramedullary site of involvement. Eight of 12 patients were diagnosed with T-ALL exhibiting a pro-/pre-T stage phenotype (CD4/CD8-double negative, CD7-positive), and frequent CD79a expression. NGS revealed pathogenic mutations in 5 of 6 tested cases, including NOTCH1, and genes in RAS and JAK-STAT pathways and epigenetic modifiers. Of 138 cases with follow-up, pediatric patients (<18 years) had 5-year overall survival (OS) of 71%, significantly better than adults at 33%. The 5-year OS for AML patients was 25%, notably shorter than T-ALL patients at 54%; this distinction was observed in both pediatric and adult populations. Furthermore, adult but not pediatric ETP-ALL patients demonstrated inferior survival compared to non-ETP-ALL patients. Neither karyotype complexity nor transplant status had a discernible impact on OS. In conclusion, PICALM::MLLT10 fusion is most commonly seen in T-ALL patients, particularly those with an ETP phenotype. AML and adult ETP-ALL patients had adverse prognosis. PICALM::MLTT10 fusion testing should be considered in T-ALL, AML, and ALAL patients.
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Leucemia Mieloide Aguda , Proteínas de Fusão Oncogênica , Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Adolescente , Proteínas de Fusão Oncogênica/genética , Criança , Pessoa de Meia-Idade , Pré-Escolar , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patologia , Leucemia-Linfoma Linfoblástico de Células T Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Idoso , Fenótipo , Predisposição Genética para Doença , Lactente , Fatores de Transcrição/genéticaRESUMO
Silver nanoparticles (AgNP) are the dominant nanomaterials in commercial products and the medical field, but the widespread occurrence of AgNP has become a global threat to human health. Growing studies indicate that AgNP exposure can induce vascular endothelial toxicity by excessive oxidative stress and inflammation, which is closely related to cardiovascular disease (CVD), but the potential intrinsic mechanism remains poorly elucidated. Thus, it has been crucial to control the toxicological effects of AgNP in order to improve their safety and increase the outcome of their applications.Multiple researches have demonstrated that sodium selenite (Se) possesses the capability to counteract the toxicity of AgNP, but the functional role of Se in AgNP-induced CVD is largely unexplored. The aim of this study was to explore the potential protective effect of Se on AgNP-induced vascular endothelial lesion and elucidate the underlying mechanisms. An in vivo model of toxicity in animals was established by the instillation of 200 µL of AgNP into the trachea of rats both with (0.2 mg/kg/day) and without Se treated. In vitro experiments, human umbilical vein endothelial cells (HUVECs) were incubated with AgNP (0.3 µg/mL ) and Se for a duration of 24 h. Utilizing transmission electron microscopy, we observed that the internalization of AgNP-induced endothelial cells was desquamated from the internal elastic lamina, the endoplasmic reticulum was dilated, and the medullary vesicle formed. Se treatment reduced the levels of vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1), inhibited the release of pro-inflammatory cytokines (specifically tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6), improved endothelial cell permeability, integrity, and dysfunction, and prevented damage to the aortic endothelium caused by AgNP. Importantly, we found that Se showed the capacity against AgNP with biological functions in guiding the intracellular reactive oxygen species (ROS) scavenging and meanwhile exhibiting anti-inflammation effects. Se supplementation decreased the intracellular ROS release and suppressed NOD-like receptor protein 3 (NLRP3) and nuclear factor kappa-B (NF-κB) mediated inflammation within AgNP-intoxicated rats and HUVECs. The anti-oxidant stress and anti-inflammatory effects of Se were at least partly dependent on nuclear factor erythroid 2-related factor 2 (Nrf2). Overall, our results indicated that the protectiveness of Se against AgNP-induced vascular endothelial toxicity injury was at least attributed to the inhibition of oxidative ROS and pro-inflammatory NF-κB/NLRP3 inflammasome by activating the Nrf2 and antioxidant enzyme (HO-1) signal pathway.
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Antioxidantes , Células Endoteliais da Veia Umbilical Humana , Inflamação , Nanopartículas Metálicas , Fator 2 Relacionado a NF-E2 , Transdução de Sinais , Prata , Selenito de Sódio , Prata/química , Prata/farmacologia , Animais , Nanopartículas Metálicas/química , Humanos , Fator 2 Relacionado a NF-E2/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Selenito de Sódio/farmacologia , Transdução de Sinais/efeitos dos fármacos , Ratos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Antioxidantes/farmacologia , Masculino , Ratos Sprague-Dawley , Estresse Oxidativo/efeitos dos fármacosRESUMO
Background: Primary percutaneous coronary intervention (PPCI) has been widely recognized as the preferred treatment for ST-segment-elevation myocardial infarction (STEMI). However, substantial numbers of STEMI patients cannot receive timely PPCI. Early fibrinolysis followed by routine percutaneous coronary intervention (FPCI) has been proposed as an effective and safe alternative for eligible patients. To date, few studies have compared FPCI with PPCI in terms of microvascular reperfusion. This study aimed to evaluate the microvascular function of FPCI and PPCI. Methods: STEMI patients at the Peking University First Hospital and Miyun Hospital were enrolled in this retrospective study between January 2015 to December 2020. Microvascular function documented by the coronary angiography-derived index of microvascular resistance (caIMR) was measured at the final angiogram after revascularization. The primary end point was the caIMR of the culprit vessels. The secondary end points were in-hospital and follow-up major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal recurrent myocardial infarction, target-vessel revascularization (TVR), and non-fatal stroke/transient ischemic attacks (TIA). Details of the adverse clinical events were obtained from telephone interviews and electronic medical record systems until January 2022. Results: In total, 496 STEMI patients were enrolled in this cross-sectional retrospective study. Of these patients, 81 underwent FPCI, and 415 underwent PPCI. At the baseline, the PPCI patients had a higher-risk profile than the FPCI patients. The time from symptom onset to reperfusion therapy was significantly shorter in the FPCI group than the PPCI group (median 3.0 vs. 4.5 hours; P<0.001). The caIMR was significantly lower in the FPCI group than the PPCI group (median 20.34 vs. 40.33; P<0.001). The median follow-up duration was 4.1 years. During the follow-up period, the rate of MACE was lower in the FPCI group than the PPCI group [7 (10.1%) vs. 82 (20.8%), P=0.048]. After propensity score matching to adjust for the imbalances at the baseline, the caIMR remained significant and the clinical outcomes did not differ significantly between the two groups. Conclusions: In eligible STEMI patients, clinically successful FPCI may be associated with better microvascular reperfusion and comparable clinical outcomes as compared with PPCI.