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1.
Blood ; 143(12): 1193-1197, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38237140

RESUMO

ABSTRACT: Many patients with antiphospholipid syndrome had decreased ectonucleotidase activity on neutrophils and platelets, which enabled extracellular nucleotides to trigger neutrophil-platelet aggregates. This phenotype was replicated by treating healthy neutrophils and platelets with patient-derived antiphospholipid antibodies or ectonucleotidase inhibitors.


Assuntos
Síndrome Antifosfolipídica , Humanos , Neutrófilos , Anticorpos Antifosfolipídeos , Plaquetas
2.
J Am Chem Soc ; 146(25): 16982-16989, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38870424

RESUMO

Catalytic asymmetric dearomatization (CADA) reactions have evolved into an efficient strategy for accessing chiral polycyclic and spirocyclic scaffolds from readily available planar aromatics. Despite the significant developments, the CADA reaction of naphthalenes remains underdeveloped. Herein, we report a Gd(III)-catalyzed asymmetric dearomatization reaction of naphthalene with a chiral PyBox ligand via visible-light-enabled [4 + 2] cycloaddition. This reaction features application of a chiral Gd/PyBox complex, which regulates the reactivity and selectivity simultaneously, in excited-state catalysis. A wide range of functional groups is compatible with this protocol, giving the highly enantioenriched bridged polycycles in excellent yields (up to 96%) and selectivity (up to >20:1 chemoselectivity, >20:1 dr, >99% ee). The synthetic utility is demonstrated by a 2 mmol scale reaction, removal of directing group, and diversifications of products. Preliminary mechanistic experiments are performed to elucidate the reaction mechanism.

3.
Clin Immunol ; 261: 109926, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38355030

RESUMO

Our study aimed to evaluate the presence, clinical associations, and potential mechanistic roles of non-criteria antiphospholipid antibodies (aPL) and circulating calprotectin, a highly stable marker of neutrophil extracellular trap release (NETosis), in pediatric APS patients. We found that 79% of pediatric APS patients had at least one non-criteria aPL at moderate-to-high titer. Univariate logistic regression demonstrated that positive anti-beta-2 glycoprotein I domain 1 (anti-D1) IgG (p = 0.008), anti-phosphatidylserine/prothrombin (aPS/PT) IgG (p < 0.001), and aPS/PT IgM (p < 0.001) were significantly associated with venous thrombosis. Positive anti-D1 IgG (p < 0.001), aPS/PT IgG (p < 0.001), and aPS/PT IgM (p = 0.001) were also associated with non-thrombotic manifestations of APS, such as thrombocytopenia. Increased levels of calprotectin were detected in children with APS. Calprotectin correlated positively with absolute neutrophil count (r = 0.63, p = 0.008) and negatively with platelet count (r = -0.59, p = 0.015). Mechanistically, plasma from pediatric APS patients with high calprotectin levels impaired platelet viability in a dose-dependent manner.


Assuntos
Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica , Humanos , Criança , Biomarcadores , beta 2-Glicoproteína I , Imunoglobulina G , Imunoglobulina M , Protrombina , Complexo Antígeno L1 Leucocitário
4.
Clin Immunol ; 255: 109714, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37527733

RESUMO

Beta-2 glycoprotein I (ß2GPI) is a phospholipid-binding plasma protein and prominent autoantigen in antiphospholipid syndrome (APS). Here, we tested the hypothesis that ß2GPI might bind to not only phospholipids, but also cell-free DNA and neutrophil extracellular traps (NETs). We report that ß2GPI interacts with cell-free DNA from different species, as well as NETs, in a dose-dependent manner, retarding their migration in an agarose-gel electrophoretic mobility shift assay. We confirm the direct binding interaction of ß2GPI with DNA and NETs by ELISA. We also demonstrate that ß2GPI colocalizes with NET strands by immunofluorescence microscopy. Finally, we provide evidence that ß2GPI-DNA complexes can be detected in the plasma of APS patients, where they positively correlate with an established biomarker of NET remnants. Taken together, our findings indicate that ß2GPI interacts with DNA and NETs, and suggest that this interaction may play a role as a perpetuator and/or instigator of autoimmunity in APS.

5.
Curr Opin Rheumatol ; 35(2): 89-97, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36580355

RESUMO

PURPOSE OF REVIEW: Antiphospholipid syndrome (APS) is an acquired thrombo-inflammatory disease associated with diverse clinical manifestations in the setting of persistently circulating antiphospholipid antibodies (aPL). This review summarizes recent developments in our understanding of the pathogenesis of APS and its various clinical manifestations with a focus on the activation of endothelial cells, complement, and neutrophils. RECENT FINDINGS: Elucidating the pathophysiology that leads to the diverse array of clinical manifestations of APS is an area of active exploration. Here, we highlight recent studies that have explored various impacts of endothelial activation and injury in APS, including the promotion of circulating endothelial cells and extracellular vesicles; the association between complement activity and different APS phenotypes, including pregnancy loss; and the relationship between neutrophil extracellular traps (NETs) and high-risk aPL profiles in thrombotic APS. We also call attention to recent work that proposes approaches to mitigating these pathologic changes as potential treatment strategies for APS. Lastly, we highlight promising future directions in APS research, such as multiomics approaches to molecularly stratifying APS patients. SUMMARY: The identification of novel aspects of pathogenesis and more nuanced approaches to phenotyping patients will hopefully pave the way for developing safer and more effective patient-specific therapeutic strategies for APS.


Assuntos
Síndrome Antifosfolipídica , Gravidez , Feminino , Humanos , Células Endoteliais , Anticorpos Antifosfolipídeos , Proteínas do Sistema Complemento , Inflamação/complicações
6.
Curr Opin Rheumatol ; 35(3): 149-160, 2023 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-36866678

RESUMO

PURPOSE OF REVIEW: Antiphospholipid syndrome (APS) is an acquired thrombo-inflammatory disease that has morbid and sometimes devastating effects on patients and their families. This review will discuss the most recent international societal treatment guidelines and propose practical management algorithms for various APS sub-types. RECENT FINDINGS: APS represents a disease spectrum. Although thrombosis and pregnancy morbidities are traditional hallmarks of APS, a variety of extra-criteria clinical phenotypes can often be seen, which makes clinical management more challenging. Primary APS thrombosis prophylaxis should take a risk-stratified approach. Although vitamin K antagonists (VKAs) or heparin/low molecular weight heparin (LMWH) remain the preferred treatment for secondary APS thrombosis prophylaxis, some international society guidelines support the use of direct oral anticoagulants (DOACs) in certain circumstances. Careful monitoring and individualized obstetric care with the use of aspirin and heparin/LMWH will improve pregnancy outcomes among pregnant individuals with APS. Treatment of microvascular and catastrophic APS remains challenging. While the addition of various immunosuppressive agents is often utilized, further systemic evaluations of their use are warranted before definitive recommendations can be made. Several new therapeutic strategies are on the horizon that might enable more personalized and targeted APS management in the near future. SUMMARY: Although the knowledge of APS pathogenesis has grown in recent years, the management principles and strategies are largely unchanged. There is an unmet need for evaluating pharmacological agents, beyond anticoagulants, that target diverse thromboinflammatory pathways.


Assuntos
Síndrome Antifosfolipídica , Trombose , Gravidez , Feminino , Humanos , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/tratamento farmacológico , Heparina de Baixo Peso Molecular/uso terapêutico , Anticoagulantes/uso terapêutico , Aspirina/uso terapêutico , Trombose/tratamento farmacológico
7.
Zhongguo Zhong Yao Za Zhi ; 48(23): 6378-6386, 2023 Dec.
Artigo em Zh | MEDLINE | ID: mdl-38211994

RESUMO

This paper aims to investigate the protective effect and mechanism of Astragalus membranaceus and Angelica sinensis before and after compatibility against triptolide(TP)-induced hepatotoxicity. The experiment was divided into a blank group, model group, Astragalus membranaceus group, Angelica sinensis group, and compatibility groups with Astragalus membranaceus/Angelica sinensis ratio of 1∶1, 2∶1, and 5∶1. TP-induced hepatotoxicity model was established, and corresponding drug intervention was carried out. The levels of alanine transaminase(ALT), aspartate transaminase(AST), and alkaline phosphatase(ALP) in serum were detected. Pathological injuries of livers were detected by hematoxylin-eosin(HE) staining. The levels of malondialdehyde(MDA), superoxide dismutase(SOD), glutathione peroxidase(GSH-Px), and reduced glutathione(GSH) in the liver were measured. Wes-tern blot method was used to detect the expression of nuclear factor erythroid 2-related factor 2(Nrf2), Kelch-like ECH-associated protein 1(Keap1), peroxisome proliferator-activated receptor gamma, coactivator-1 alpha(PGC-1α), heme oxygenase-1(HO-1), and NAD(P)H quinone dehydrogenase 1(NQO1) in livers. Immunofluorescence was used to detect the expression of Nrf2 and PGC-1α in livers. The results indicated that Astragalus membranaceus/Angelica sinensis ratio of 2∶1 and 5∶1 could significantly reduce the levels of serum AST, ALT, and ALP, improve the pathological damage of liver tissue, increase the levels of GSH and GSH-Px, and reduce the content of MDA in liver tissue. Astragalus membranaceus/Angelica sinensis ratio of 1∶1 and 2∶1 could significantly improve the level of SOD. Astragalus membranaceus and Angelica sinensis before and after compatibility significantly increased the protein expression of HO-1 and NQO1, improved the protein expression of Nrf2 and PGC-1α, and decreased the protein expression of Keap1 in liver tissue. The above results confirmed that the compatibility of Astragalus membranaceus and Angelica sinensis had antioxidant effects by re-gulating Keap1/Nrf2/PGC-1α, and the Astragalus membranaceus/Angelica sinensis ratio of 2∶1 and 5∶1 had stronger antioxidant effect and significantly reduced TP-induced hepatoto-xicity.


Assuntos
Angelica sinensis , Doença Hepática Induzida por Substâncias e Drogas , Diterpenos , Fenantrenos , Humanos , Astragalus propinquus , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Superóxido Dismutase/metabolismo , Estresse Oxidativo , Compostos de Epóxi
8.
J Transl Med ; 20(1): 91, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35168617

RESUMO

BACKGROUND: Prostate cancer is the second most common cancer in men, and some new target genes are needed to predict the risk of prostate cancer progression and the treatment. METHODS: In this study, the effects of UAP1L1 (UAP1-like-1) on prostate cancer were investigated by detecting the proliferation, migration, invasion and apoptosis of prostate cancer cells in vitro using MTT, wound healing, Transwell and flow cytometry assay, and the tumor growth in vivo. The downstream genes and pathways of UAP1L1 were explored using Ingenuity Pathway Analysis (IPA), and screened by qRT-PCR and western blot. The effects of CDCA8 on prostate cancer cells were also verified in vitro, which was through detecting the change of proliferation, migration, invasion and apoptosis of prostate cancer cells after CDCA8 knockdown. RESULTS: The results indicated that UAP1L1 promoted the proliferation, migration and invasion of prostate cancer cells, which was inhibited by downregulating CDCA8. Furthermore, the promotion of CDCA8 knockdown on cell apoptosis was reduced when UAP1L1 was simultaneously overexpressed. CONCLUSIONS: In conclusion, the results in this study revealed that UAP1L1 promoted the progression of prostate cancer through the downstream gene CDCA8.


Assuntos
Neoplasias da Próstata , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Neoplasias da Próstata/patologia
9.
Rheumatology (Oxford) ; 61(12): 4962-4974, 2022 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-35325077

RESUMO

OBJECTIVE: Leucocyte immunoglobulin-like receptor A3 (LILRA3) belongs to a family of leucocyte receptors. Our previous study reported LILRA3 transcripts were markedly upregulated in neutrophils from patients with APS. We undertook this study to investigate clinical implications of LILRA3 in APS and its potential role in APS-associated thrombosis. METHODS: Two independent cohorts were studied. The first consisted of 294 APS patients, 48 asymptomatic aPL carriers and 150 healthy controls (HCs) from Peking University People's Hospital. The second included 99 APS patients, 25 aPL carriers and 40 HCs from United States APS centres. Serum or plasma concentrations of LILRA3 and MPO-DNA complexes were measured. Additionally, 35 patients with thrombotic APS (tAPS) were evaluated to determine potential effects of immunosuppressive therapy on serum concentrations of LILRA3 and MPO-DNA complexes. RESULTS: Both positivity and serum concentration of LILRA3 were significantly increased in APS patients, especially in those with tAPS. LILRA3-positive tAPS patients displayed more severe thrombotic manifestations. Serum LILRA3 was positively correlated with MPO-DNA complexes in LILRA3-positive tAPS. After immunosuppressive treatment, LILRA3 and MPO-DNA complexes were consistently decreased in tAPS patients. Key findings from the Peking cohort were confirmed in the United States cohort. CONCLUSION: Our study provides first evidence that LILRA3 is aberrantly expressed in APS, especially in patients with tAPS. Serum LILRA3 correlated with MPO-DNA complexes, and the two indices were consistently decreased in tAPS patients after treatment. LILRA3 may play a role in thrombosis of APS and may serve as a biomarker and/or therapeutic target in tAPS.


Assuntos
Síndrome Antifosfolipídica , Trombose , Humanos , Síndrome Antifosfolipídica/complicações , Anticorpos Antifosfolipídeos , Trombose/etiologia , Trombose/tratamento farmacológico , Biomarcadores , Estudos de Coortes , Receptores Imunológicos
10.
Lupus ; 31(14): 1770-1776, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36206383

RESUMO

BACKGROUND/PURPOSE: APS ACTION Registry was created to study the outcomes of patients with persistently positive antiphospholipid antibodies (aPL) with or without other systemic autoimmune disease (SAIDx). Given that immunosuppression (IS) is used for certain aPL manifestations, for example, thrombocytopenia (TP), our primary objective was to describe the indications for IS in aPL-positive patients without other SAIDx. Secondly, we report the type of IS used in patients with selected microvascular or non-thrombotic aPL manifestations. METHODS: An online database is used to collect clinical data. The inclusion criteria are positive aPL based on the laboratory section of the APS Classification Criteria, tested at least twice within one year prior to enrollment. Patients are followed every 12 ± 3 months. For this descriptive retrospective and prospective analysis, we included aPL-positive patients without other SAIDx and excluded those with new SAIDx classification during follow-up. For each patient, we retrieved clinical data at baseline and follow-up including selected aPL manifestations (diffuse alveolar hemorrhage [DAH], antiphospholipid-nephropathy [aPL-N], livedoid vasculopathy [LV]-related skin ulcers, TP, autoimmune hemolytic anemia [AIHA], cardiac valve disease [VD]), and IS medications. RESULTS: Of 899 patients enrolled, 537 were included in this analysis (mean age 45 ± 13 years, female 377 [70%], APS Classification in 438 [82%], and at least one selected microvascular or non-thrombotic aPL manifestation in 141 (26%)). Of 537 patients, 76 (14%) were reported to use IS (ever), and 41/76 (54%) received IS primarily for selected aPL manifestation. In six of 8 (75%) DAH patients, 6/19 (32%) aPL-N, 4/28 (14%) LV, 25/88 (28%) TP, 6/11 (55%) AIHA, and 1/43 (2%) VD, the IS (excluding corticosteroids/hydroxychloroquine) indication was specific for selected aPL manifestation. CONCLUSION: In our international cohort, 14% of aPL-positive patients without other SAIDx were reported to receive IS; the indication was at least one of the selected microvascular and/or non-thrombotic aPL-related manifestations in half. Thrombocytopenia was the most frequent among those selected aPL-related manifestations; however, approximately one-third received IS specifically for that indication. Diffuse alveolar hemorrhage was frequently treated with IS followed by AIHA and aPL-N. Systematic controlled studies are urgently needed to better define the role of IS in APS.


Assuntos
Síndrome Antifosfolipídica , Lúpus Eritematoso Sistêmico , Trombocitopenia , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Síndrome Antifosfolipídica/tratamento farmacológico , Estudos Retrospectivos , Anticorpos Antifosfolipídeos , Terapia de Imunossupressão
11.
Clin Exp Rheumatol ; 40(2): 284-291, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34796847

RESUMO

OBJECTIVES: The clinical features of myositis specific antibody negative dermatomyositis (MSA negative DM) varied greatly, and there were few reports in the literatures. This study aimed to describe and expand the clinical phenotypes and prognoses of MSA negative DM patients. METHODS: MSA negative DM patients were identified from January 2010 to June 2020. We retrospectively reviewed the clinical features and laboratory data. The survival status was followed up until July 31. 2020 SPSS version 21.0 and R version 3.6.1 software were used for the statistical analyses. RESULTS: A total of 97 MSA negative DM patients were enrolled. The most common type of rashes was heliotrope rash (80.4%). More than half of the patients (55.7%) had interstitial lung disease (ILD), and seven of them developed rapid progressive ILD. There were eleven patients with tumours. During the follow-up, twelve patients died, of whom 5 (41.7%) died due to infection. Two phenotypes of MSA negative DM patients were identified by cluster analysis. Patients in cluster 1 developed muscle weakness, mechanic's hands, arthritis, and ILD more frequently. Patients in cluster 2 had a higher incidence of heliotrope rashes. Patients in cluster 1 tended to have worse prognoses, wherein the 1-year and 5-year survival rates (81.1% and 78.4%, respectively) were lower than those in cluster 2 (97.6% and 95.2%, respectively), with p value 0.04 and 0.056 respectively. CONCLUSIONS: Through cluster analysis, different clinical phenotypes of MSA negative DM patients were determined. The prognoses of the two subgroups were different in terms of survival rate and cause of death.


Assuntos
Dermatomiosite , Miosite , Autoanticorpos , Dermatomiosite/diagnóstico , Dermatomiosite/epidemiologia , Dermatomiosite/terapia , Humanos , Prognóstico , Estudos Retrospectivos
12.
Skeletal Radiol ; 51(6): 1303-1312, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34757481

RESUMO

OBJECTIVE: To evaluate the utility of multidetector computed tomography MDCT quantitative measurements in identifying sarcopenia. MATERIALS AND METHODS: The clinical data and MDCT images of 64 patients of sarcopenia and 184 non-sarcopenic participants between October 2020 and January 2021were retrospectively analyzed. Propensity score matching was used to match the sarcopenic patients with the non-sarcopenic participants. Two radiologists independently measured the cross-sectional area (CSA) of skeletal muscle and intramuscular fat tissue and CT density of skeletal muscle at the middle L3 vertebral level on CT images of all participants. Intra-observer agreement was evaluated via intraclass correlation coefficients (ICC). A receiver operating characteristic (ROC) curve was built for each variable. Correlations between CT parameters and clinical data were assessed via Pearson or Spearman correlation coefficient. RESULTS: A total of 74 participants (mean age 72 ± 4 years, range 66-85 years; 38 men and 36 women) were included, comprising 37 sarcopenic patients and 37 non-sarcopenic participants. There were no significant intergroup differences regarding age, sex ratio, and body mass index (BMI) (P < 0.05). The CSA and density of skeletal muscle measured by two radiologists were reliable (ICC ≥ 0.75, P < 0.001). Compared with the sarcopenic group, the non-sarcopenic group had a significantly greater CSA and CT density of the total skeletal muscle (TSM) and paraspinal skeletal muscle (PSM) and skeletal muscle index at L3 level (L3 SMI) (P < 0.05). The fat infiltration ratio (FIR) of TSM, PSM, and psoas muscle was significantly higher in the sarcopenic group than that in non-sarcopenic participants (P < 0.05). ROC curve analysis showed the PSM FIR + PSM CT density (PSM D) had the best predictive value for sarcopenia (AUC = 0.836). The PSM FIR and age were moderately positively correlated (r = 0.410, P < 0.001). CONCLUSION: Fat infiltration of skeletal muscle had better predictive value than L3 SMI in the diagnosis of sarcopenic. The PSM FIR + PSMD had the best predictive value for sarcopenia, which was moderately positively correlated with age.


Assuntos
Sarcopenia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Tomografia Computadorizada Multidetectores , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/patologia , Pontuação de Propensão , Músculos Psoas/diagnóstico por imagem , Estudos Retrospectivos , Sarcopenia/diagnóstico por imagem
13.
Lupus ; 30(5): 828-832, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33736541

RESUMO

BACKGROUND: Antiphospholipid antibodies (aPL) have been extensively reported in children, but investigations into thrombotic risks associated with aPL positivity in pediatric patients is scarce. Positive aPL are not uncommon in pediatric connective tissue diseases (CTD), but identification and management of these patients is challenging due to lack of validated criteria and a paucity of data. In this study, we identify potential additional risk factors for thrombosis in a unique cohort of pediatric aPL positive carriers. METHODS: Retrospective chart review was performed on 491 pediatric patients with CTD seen in our institution from 2001 to 2019. Patients without persistently moderate to high titer aPL at least 12 weeks apart were excluded. Univariate analysis was performed to evaluate correlation between different risk factors and thrombotic events. RESULTS: Seventy-one aPL positive children with underlying CTD are included in this cohort. The majority (87%) are female and of Hispanic ethnicity (56%). Mean age of the cohort at the diagnosis of connective tissue disease is 12.7 (SD 2.6) years, and mean age of first positive aPL is 13.3 (SD 2.5) years. Average length of follow-up is 4.3 (SD 2.5) years. Four (5.6%) patients experienced arterial thrombosis, and 11 (15.5%) had venous thrombosis. Fifty-seven (80.3%) patients did not have any thromboembolic events. Among traditional risk factors and signs of endothelial injury, only Raynaud's phenomena demonstrated significant association with arterial thrombosis (OR = 8.4, 95%CI 1.13-111, P = 0.039), and hypertension or anti-hypertensive use demonstrated significant association with venous thrombosis (OR = 8.387, 95%CI 1.2 - 94, P = 0.02). CONCLUSION: Data from our cohort suggest that Raynaud's phenomenon is a potential predictor of arterial thrombosis while the presence of hypertension or anti-hypertensive medication use is a potential predictor of venous thrombosis in aPL positive pediatric carriers. Further studies investigating pediatric aPL profiles and risk factors for development of thrombosis are needed to help guide clinicians in caring for these challenging patients.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Doenças do Tecido Conjuntivo/imunologia , Trombose/imunologia , Trombose Venosa/imunologia , Adolescente , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/uso terapêutico , Síndrome Antifosfolipídica/complicações , Artérias/patologia , Portador Sadio/sangue , Criança , Doenças do Tecido Conjuntivo/complicações , Doenças do Tecido Conjuntivo/diagnóstico , Doenças do Tecido Conjuntivo/patologia , Feminino , Seguimentos , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Inibidor de Coagulação do Lúpus/sangue , Lúpus Eritematoso Sistêmico/complicações , Masculino , Doença de Raynaud/complicações , Doença de Raynaud/diagnóstico , Doença de Raynaud/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Trombose/diagnóstico , Trombose/epidemiologia , Trombose Venosa/epidemiologia
14.
Lupus ; 30(14): 2276-2285, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34915764

RESUMO

Coronavirus disease 2019 (COVID-19) is associated with a high rate of thrombosis. Prolonged activated partial thromboplastin times (aPTT) and antiphospholipid antibodies (aPL) are reported in COVID-19 patients. The majority of publications have not reported whether patients develop clinically relevant persistent aPL, and the clinical significance of new aPL-positivity in COVID-19 is currently unknown. However, the reports of aPL-positivity in COVID-19 raised the question whether common mechanisms exist in the pathogenesis of COVID-19 and antiphospholipid syndrome (APS). In both conditions, thrombotic microangiopathy resulting in microvascular injury and thrombosis is hypothesized to occur through multiple pathways, including endothelial damage, complement activation, and release of neutrophil extracellular traps (NETosis). APS-ACTION, an international APS research network, created a COVID-19 working group that reviewed common mechanisms, positive aPL tests in COVID-19 patients, and implications of COVID-19 infection for patients with known aPL positivity or APS, with the goals of proposing guidance for clinical management and monitoring of aPL-positive COVID-19 patients. This guidance also serves as a call and focus for clinical and basic scientific research.


Assuntos
Anticorpos Antifosfolipídeos , Síndrome Antifosfolipídica , COVID-19 , Trombose , COVID-19/patologia , Humanos , Trombose/virologia
15.
Arch Virol ; 166(8): 2159-2171, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34031716

RESUMO

Porcine circovirus type 2 (PCV2) is the primary causative agent of porcine circovirus-associated diseases in swine, the most common of which are postweaning multisystemic wasting syndrome (PMWS) and porcine dermatitis and nephropathy syndrome (PDNS). To investigate the prevalence and genetic diversity of PCV2 in Hebei Province, Northern China, from 2016 to 2019, a total of 448 suspected cases of PCV2 infection were studied, and 179 samples were positive for PCV2. A pathological and histopathological examination suggested PCV2 to be cause of the observed lesions. Phylogenetic analysis showed that four genotypes were prevalent in Hebei Province: PCV2a, 2b, 2d, and 2e. Analysis of PCV2 strains using RDP4 and SimPlot showed that there were genetic recombination events among PCV2 strains in Hebei Province. A total of 3284 serum samples were screened by ELISA, and the positive rate of PCV2 antibodies was 73.9% (2428/3284). This study provides a scientific reference for the prevention and treatment of PCV2 in Hebei Province.


Assuntos
Anticorpos Antivirais/sangue , Infecções por Circoviridae/veterinária , Circovirus/classificação , Síndrome Definhante Multissistêmico de Suínos Desmamados/epidemiologia , Animais , China/epidemiologia , Infecções por Circoviridae/sangue , Circovirus/genética , Circovirus/isolamento & purificação , Variação Genética , Filogenia , Síndrome Definhante Multissistêmico de Suínos Desmamados/virologia , Prevalência , Estudos Retrospectivos , Análise de Sequência de DNA , Suínos
16.
J Thromb Thrombolysis ; 51(2): 446-453, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33151461

RESUMO

Studies of patients with COVID-19 have demonstrated markedly dysregulated coagulation and a high risk of morbid arterial and venous thrombotic events. Elevated levels of blood neutrophils and neutrophil extracellular traps (NETs) have recently been described in patients with COVID-19. However, their potential role in COVID-19-associated thrombosis remains incompletely understood. In order to elucidate the potential role of hyperactive neutrophils and NET release in COVID-19-associated thrombosis, we conducted a case-control study of patients hospitalized with COVID-19 who developed thrombosis, as compared with gender- and age-matched COVID-19 patients without clinical thrombosis. We found that remnants of NETs (cell-free DNA, myeloperoxidase-DNA complexes, and citrullinated histone H3) and neutrophil-derived S100A8/A9 (calprotectin) in patient sera were associated with higher risk of morbid thrombotic events in spite of prophylactic anticoagulation. These observations underscore the need for urgent investigation into the potential relationship between NETs and unrelenting thrombosis in COVID-19, as well as novel approaches for thrombosis prevention.


Assuntos
COVID-19/sangue , Armadilhas Extracelulares/metabolismo , Neutrófilos/metabolismo , SARS-CoV-2/metabolismo , Trombose/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , COVID-19/complicações , Estudos de Casos e Controles , Feminino , Histonas/sangue , Humanos , Complexo Antígeno L1 Leucocitário/sangue , Masculino , Pessoa de Meia-Idade , Trombose/etiologia
17.
Appl Opt ; 60(29): 9180-9187, 2021 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-34624000

RESUMO

A single-pixel neural network object classification scenario in the sub-Nyquist ghost imaging system is proposed. Based on the neural network, objects are classified directly by bucket measurements without reconstructing images. Classification accuracy can still be maintained at 94.23% even with only 16 measurements (less than the Nyquist limit of 1.56%). A parallel computing scheme is applied in data processing to reduce the object acquisition time significantly. Random patterns are used as illumination patterns to illuminate objects. The proposed method performs much better than existing methods for both binary and grayscale images in the sub-Nyquist condition, which is also robust to environment noise turbulence. Benefiting from advantages of ghost imaging, it may find applications for target recognition in the fields of remote sensing, military defense, and so on.

18.
Sensors (Basel) ; 21(14)2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34300634

RESUMO

Palmprint recognition has received tremendous research interests due to its outstanding user-friendliness such as non-invasive and good hygiene properties. Most recent palmprint recognition studies such as deep-learning methods usually learn discriminative features from palmprint images, which usually require a large number of labeled samples to achieve a reasonable good recognition performance. However, palmprint images are usually limited because it is relative difficult to collect enough palmprint samples, making most existing deep-learning-based methods ineffective. In this paper, we propose a heuristic palmprint recognition method by extracting triple types of palmprint features without requiring any training samples. We first extract the most important inherent features of a palmprint, including the texture, gradient and direction features, and encode them into triple-type feature codes. Then, we use the block-wise histograms of the triple-type feature codes to form the triple feature descriptors for palmprint representation. Finally, we employ a weighted matching-score level fusion to calculate the similarity between two compared palmprint images of triple-type feature descriptors for palmprint recognition. Extensive experimental results on the three widely used palmprint databases clearly show the promising effectiveness of the proposed method.


Assuntos
Identificação Biométrica , Algoritmos , Bases de Dados Factuais , Mãos/anatomia & histologia
19.
Curr Opin Rheumatol ; 32(3): 215-227, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32187042

RESUMO

PURPOSE OF REVIEW: Antiphospholipid syndrome (APS), more common than once believed, is an autoimmune disease best known for its high risk of incident and recurrent thrombotic events. The approach to treatment potentially differs from treatment of thrombosis in the general population, and this article endeavors to review the latest updates on this topic. RECENT FINDINGS: The epidemiology of APS is being increasingly elucidated by large population-based studies, with APS perhaps affecting as many as 1 in 2000 individuals. Vitamin K antagonists, aspirin, and heparinoids continue to have obvious roles in the management of patients with APS. There has recently been intensive study of direct oral anticoagulants in APS, with the most recent randomized studies raising concerns about their inferiority to vitamin K antagonists, at least in some subgroups. Other approaches to treating APS beyond anticoagulants and antiaggregants are also receiving increased attention in mechanistic and preclinical studies with an eye toward future roles in patients with refractory and/or microvascular disease. Pediatric APS is identified as an area in desperate need of additional prospective research. SUMMARY: Progress continues to be made in pursuit of improving the lives of individuals afflicted with APS. The most important future directions would seem to involve leveraging modern molecular technologies in order to improve subphenotyping of antiphospholipid antibody-positive individuals. This will help personalize risk profiles and ideally define the optimal approach to therapy based on future risk, rather than past morbid events.


Assuntos
Anticoagulantes/uso terapêutico , Síndrome Antifosfolipídica/tratamento farmacológico , Aspirina/uso terapêutico , Trombose/tratamento farmacológico , Vitamina K/antagonistas & inibidores , Adulto , Síndrome Antifosfolipídica/imunologia , Criança , Humanos , Estudos Prospectivos , Trombose/imunologia
20.
Rheumatology (Oxford) ; 59(10): 2829-2837, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32065646

RESUMO

OBJECTIVES: To evaluate the distribution of radiological characteristics stratified by different myositis-specific autoantibodies, identify prognostic value of high-resolution CT (HRCT) patterns in DM-associated interstitial lung disease (DM-ILD), and explore the possible mechanism associated with macrophage activation. METHODS: We enrolled 165 patients with PM/DM-ILD. The distribution of HRCT radiological types with different myositis-specific autoantibodies and the relationship between radiological features and ILD course and prognosis were analysed. Additionally, the potential role of macrophage activation in rapidly progressive ILD (RP-ILD) with DM was studied. RESULTS: The organizing pneumonia pattern was dominant in HRCT findings of patients with DM-ILD, especially those with anti-SAE (6/6, 100%) and anti-MDA5 (46/62, 74.2%) antibodies. The ratios of organizing pneumonia and nonspecific interstitial pneumonia patterns were almost equal in patients with aminoacyl tRNA synthetase antibodies, and nonspecific interstitial pneumonia pattern was associated with a mild clinical course. Lower lung zone consolidation in HRCT was related to RP-ILD in both anti-MDA5 and anti-aminoacyl tRNA synthetase antibody-positive groups. Ferritin levels of >1000 ng/ml (odds ratio (OR), 12.3; P=0.009), elevated carcinoembryonic antigen (OR, 5.8; P=0.046) and carbohydrate antigen 19-9 (OR, 7.8; P=0.018) were independent predictors of a lower lung zone consolidation pattern in anti-MDA5 antibody-positive DM. The infiltration of CD163-positive macrophages into alveolar spaces was significantly higher in the DM-RP-ILD group than in the chronic DM-ILD group. CONCLUSION: HRCT patterns are different among variable myositis-specific autoantibodies positive patients with ILD and lower zone consolidation in HRCT correlated with RP-ILD in DM. Activated macrophages may contribute to the pathogenesis of RP-ILD in DM.


Assuntos
Dermatomiosite/complicações , Dermatomiosite/imunologia , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Doenças Pulmonares Intersticiais/imunologia , Ativação de Macrófagos , Doença Aguda , Idade de Início , Especificidade de Anticorpos , Autoanticorpos/análise , Doença Crônica , Dermatomiosite/sangue , Progressão da Doença , Feminino , Ferritinas/sangue , Humanos , Helicase IFIH1 Induzida por Interferon/imunologia , Ligases/imunologia , Doenças Pulmonares Intersticiais/sangue , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
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