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1.
Lancet Infect Dis ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38663423

RESUMO

BACKGROUND: Growing evidence suggests that symptoms associated with post-COVID-19 condition (also known as long COVID) can affect multiple organs and systems in the human body, but their association with viral persistence is not clear. The aim of this study was to investigate the persistence of SARS-CoV-2 in diverse tissues at three timepoints following recovery from mild COVID-19, as well as its association with long COVID symptoms. METHODS: This single-centre, cross-sectional cohort study was done at China-Japan Friendship Hospital in Beijing, China, following the omicron wave of COVID-19 in December, 2022. Individuals with mild COVID-19 confirmed by PCR or a lateral flow test scheduled to undergo gastroscopy, surgery, or chemotherapy, or scheduled for treatment in hospital for other reasons, at 1 month, 2 months, or 4 months after infection were enrolled in this study. Residual surgical samples, gastroscopy samples, and blood samples were collected approximately 1 month (18-33 days), 2 months (55-84 days), or 4 months (115-134 days) after infection. SARS-CoV-2 was detected by digital droplet PCR and further confirmed through RNA in-situ hybridisation, immunofluorescence, and immunohistochemistry. Telephone follow-up was done at 4 months post-infection to assess the association between the persistence of SARS-CoV-2 RNA and long COVID symptoms. FINDINGS: Between Jan 3 and April 28, 2023, 317 tissue samples were collected from 225 patients, including 201 residual surgical specimens, 59 gastroscopy samples, and 57 blood component samples. Viral RNA was detected in 16 (30%) of 53 solid tissue samples collected at 1 month, 38 (27%) of 141 collected at 2 months, and seven (11%) of 66 collected at 4 months. Viral RNA was distributed across ten different types of solid tissues, including liver, kidney, stomach, intestine, brain, blood vessel, lung, breast, skin, and thyroid. Additionally, subgenomic RNA was detected in 26 (43%) of 61 solid tissue samples tested for subgenomic RNA that also tested positive for viral RNA. At 2 months after infection, viral RNA was detected in the plasma of three (33%), granulocytes of one (11%), and peripheral blood mononuclear cells of two (22%) of nine patients who were immunocompromised, but in none of these blood compartments in ten patients who were immunocompetent. Among 213 patients who completed the telephone questionnaire, 72 (34%) reported at least one long COVID symptom, with fatigue (21%, 44 of 213) being the most frequent symptom. Detection of viral RNA in recovered patients was significantly associated with the development of long COVID symptoms (odds ratio 5·17, 95% CI 2·64-10·13, p<0·0001). Patients with higher virus copy numbers had a higher likelihood of developing long COVID symptoms. INTERPRETATION: Our findings suggest that residual SARS-CoV-2 can persist in patients who have recovered from mild COVID-19 and that there is a significant association between viral persistence and long COVID symptoms. Further research is needed to verify a mechanistic link and identify potential targets to improve long COVID symptoms. FUNDING: National Natural Science Foundation of China, National Key R&D Program of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and New Cornerstone Science Foundation. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

4.
J Int Med Res ; 52(1): 3000605231223441, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38258803

RESUMO

OBJECTIVE: To evaluate the safety and efficacy of bleomycin polidocanol foam (BPF) sclerotherapy for venous malformations (VMs) and analyze the associated clinical outcomes and predictors. METHODS: We retrospectively assessed BPF sclerotherapy outcomes in 138 patients with VMs. We analyzed pain levels, lesion volume reduction, and subjective perception of response. Logistic regression analysis was performed to identify potential predictors of treatment outcome. Additionally, we carefully monitored and recorded complications. RESULTS: There was a notable average reduction in lesion volume by 78.50% ± 15.71%. The pain numerical rating scale (NRS) score decreased from 4.17 ± 2.63 prior to treatment to 1.05 ± 1.54 afterward, and 70.3% of the patients experienced effective relief after a single BPF treatment. Multivariate analysis revealed that a high baseline NRS (odds ratio [OR]: 4.026) and elevated activated partial thromboplastin time (APTT, OR: 1.200) were positive predictors of pain reduction. Additionally, a high baseline NRS score (OR: 1.992) and elevated thrombocytocrit (PCT, OR: 2.543) were positive predictors of incomplete postoperative pain relief. Minor complications occurred in 31 (22.46%) patients. CONCLUSION: BPF sclerotherapy is safe and effective for VMs, resulting in significant reduction in lesion volume, improved symptoms, and minimal complications. APTT and PCT levels are important predictors of pain outcomes following BPF treatment.


Assuntos
Bleomicina , Polietilenoglicóis , Escleroterapia , Humanos , Bleomicina/uso terapêutico , Polidocanol , Estudos Retrospectivos , Dor/etiologia
5.
J Vasc Surg Venous Lymphat Disord ; 12(2): 101697, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37890588

RESUMO

OBJECTIVE: This study aims to investigate the difference in safety and efficacy between two treatments for venous malformations (VMs), electrochemotherapy combined with polidocanol foam (ECP) and bleomycin polidocanol foam (BPF), providing alternative therapies for VMs. METHODS: We conducted a retrospective review of 152 patients with VMs treated with ECP and BPF. Pre- and post-treatment magnetic resonance images (MRIs) were collected, and clinical follow-up assessments were performed. Imaging results were used to calculate lesion volume changes. Clinical outcomes included changes in pain and improvements in perceived swelling. Patients were followed up at 1 week and 6 months after surgery. All emerging complications were documented in detail. RESULTS: Of the 152 patients, 87 (57.2%) received BPF treatment, and 65 (42.8%) received ECP treatment. The most common location of VMs was the lower extremities (92/152; 60.2%), and the most common symptom was pain (108/152; 71.1%). Forty-three patients had previously undergone therapy in the BPF group (43/87; 49.4%), whereas 30 patients had received prior treatment in the ECP group (30/65; 46.2%). The study found that the percentage of lesion volume reduction in the BPF group was not significantly different from that in the ECP group (75.00% ± 17.85% vs 74.69% ± 8.48%; P = .899). ECP was more effective when the initial lesion volume was greater than 30 mL (67.66% ± 12.34% vs 73.47% ± 8.00%; P = .048). Patients treated with BPF had significantly less posttreatment pain than those treated with ECP, in different baseline lesion size. In the overall sample, pain relief was significantly higher in the BPF group than in the ECP group (4.21 ± 1.19 vs 3.57 ± 0.76; P = .002). However, there was no difference in pain relief between the two groups for the treatment of initially large VMs (4.20 ± 0.94 vs 3.70 ± 0.87; P = .113). The ECP group was significantly more likely to develop hyperpigmentation (5/87; 5.75% vs 11/65; 16.92%; P = .026) and swelling (9/87; 10.34% vs 16/65; 24.62%; P = .019) 1 week after surgery than the BPF group. CONCLUSIONS: Our study demonstrates that both BPF and ECP are effective treatments for VMs, with BPF being a safer option. ECP is a better choice for patients with the initial lesion volume greater than 30 mL, but it is more likely to lead to early swelling and hyperpigmentation.


Assuntos
Eletroquimioterapia , Hiperpigmentação , Polietilenoglicóis , Malformações Vasculares , Humanos , Polidocanol/efeitos adversos , Soluções Esclerosantes , Bleomicina/efeitos adversos , Escleroterapia/efeitos adversos , Escleroterapia/métodos , Eletroquimioterapia/efeitos adversos , Malformações Vasculares/diagnóstico por imagem , Malformações Vasculares/terapia , Malformações Vasculares/complicações , Resultado do Tratamento , Dor/etiologia , Estudos Retrospectivos , Hiperpigmentação/etiologia
6.
Front Physiol ; 14: 1207390, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37727659

RESUMO

Objective: This study aimed to investigate the plasma metabolic profile of patients with extracranial arteriovenous malformations (AVM). Method: Plasma samples were collected from 32 AVM patients and 30 healthy controls (HC). Ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) was employed to analyze the metabolic profiles of both groups. Metabolic pathway enrichment analysis was performed through Kyoto Encyclopedia of Genes and Genomes (KEGG) database and MetaboAnalyst. Additionally, machine learning algorithms such as Least Absolute Shrinkage and Selection Operator (LASSO) and random forest (RF) were conducted to screen characteristic metabolites. The effectiveness of the serum biomarkers for AVM was evaluated using a receiver-operating characteristics (ROC) curve. Result: In total, 184 differential metabolites were screened in this study, with 110 metabolites in positive ion mode and 74 metabolites in negative mode. Lipids and lipid-like molecules were the predominant metabolites detected in both positive and negative ion modes. Several significant metabolic pathways were enriched in AVMs, including lipid metabolism, amino acid metabolism, carbohydrate metabolism, and protein translation. Through machine learning algorithms, nine metabolites were identify as characteristic metabolites, including hydroxy-proline, L-2-Amino-4-methylenepentanedioic acid, piperettine, 20-hydroxy-PGF2a, 2,2,4,4-tetramethyl-6-(1-oxobutyl)-1,3,5-cyclohexanetrione, DL-tryptophan, 9-oxoODE, alpha-Linolenic acid, and dihydrojasmonic acid. Conclusion: Patients with extracranial AVMs exhibited significantly altered metabolic patterns compared to healthy controls, which could be identified using plasma metabolomics. These findings suggest that metabolomic profiling can aid in the understanding of AVM pathophysiology and potentially inform clinical diagnosis and treatment.

7.
J Cell Physiol ; 238(8): 1808-1822, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37475193

RESUMO

Hyperuricemia closely correlates with the development of atherosclerosis, but little is known of the mechanism by which atherosclerosis progression occurs in hyperuricemia. Atherosclerosis appears to involve pyroptosis, an emerging mechanism of proinflammatory regulated cell death. This study tested the hypothesis that pyroptosis underlies the relationship between hyperuricemia and atherosclerosis, using ApoE-/- mice (a model of atherosclerosis), human umbilical vein endothelial cells (HUVECs), and human atherosclerotic arterial samples. We found that hyperuricemia can aggravate the aortic atherosclerotic plaque-load in ApoE-/- mice and promote endothelial cell pyroptosis. Additionally, hyperuricemia can increase the levels of serum inflammatory factors (including IL-1ß and IL-18). Exposure to lipopolysaccharide plus a high concentration of soluble uric acid (≥12 mg/dL) induced cell pyroptosis in HUVECs, as evidenced by increased expression of pyroptosis-related proteins and elevated release of lactate dehydrogenase (a marker of tissue damage). Further, MCC950, a selective nucleotide-binding oligomerization domain (NOD)-like receptor 3 (NLRP3) inflammasome inhibitor, and N-acetyl- l-cysteine, an antioxidant, attenuated HUVEC pyroptosis by inhibiting activation of the NLRP3 inflammasome and production of intracellular reactive oxygen species (ROS). Finally, we detected significantly higher expression of pyroptosis-associated proteins in carotid specimens from patients with hyperuricemia. Collectively, our findings suggest that hyperuricemia can aggravate endothelial cell pyroptosis in aortic atherosclerotic plaques, promoting the development of atherosclerosis. Additionally, a high concentration of soluble uric acid can trigger the activation stage of the NLRP3 inflammasome, mediating endothelial cell pyroptosis, and this process is regulated by the cellular ROS level.


Assuntos
Aterosclerose , Hiperuricemia , Humanos , Camundongos , Animais , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Piroptose , Ácido Úrico/metabolismo , Hiperuricemia/complicações , Células Endoteliais da Veia Umbilical Humana/metabolismo , Aterosclerose/metabolismo , Apolipoproteínas E/metabolismo
8.
Chem Commun (Camb) ; 59(63): 9654-9657, 2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37466352

RESUMO

A Gd-doped ultrasmall CeO2 contrast agent was prepared with high longitudinal relaxivity (r1 = 10.1 mM-1 s-1, 7.0 T) through rationally regulating the crystallinity and surface coatings, providing a new paradigm for optimizing MRI performance. Moreover, responsive photoacoustic imaging (PAI) was established via tumor microenvironment-triggered oxidation, affording dual-modal imaging.

9.
J Vasc Surg Venous Lymphat Disord ; 11(1): 143-148, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35940448

RESUMO

OBJECTIVE: The objective of this research was to retrospectively investigate the difference of safety and efficacy between polidocanol foam and bleomycin polidocanol foam (BPF) in the treatment of venous malformations (VMs), and provide clinical evidence for the application of BPF for VMs. METHODS: Patients with VMs treated with polidocanol foam and BPF were included between July 2018 and July 2020. The VM tissue involvements and symptoms were collected. The treatment outcomes were evaluated by the clinical improvement of symptoms and the degree of devascularization on ultrasound examination or magnetic resonance imaging. Patients were followed up for 1, 3, and 6 months after the sclerotherapy. Immediate and delayed complications were closely followed and recorded. RESULTS: A total of 51 patients were included, including 34 females and 17 males with a mean age of 26.8 years (range, 5-65 years). The most commonly involved sites were lower extremities (31/60 [51.7%]) and the most common symptom was pain (33/51 [64.7%]). Fifty-four sclerotherapies were performed with a mean of 1.06 ± 0.24 sessions (range, 1-2 sessions) per patient. The reduction percentage of lesion volume in the BPF group was significantly higher than the polidocanol foam group (79.4 ± 1.6% vs 55.7 ± 6.1%; P < .001). Patient satisfaction scores in the BPF group were significantly higher than the polidocanol foam group (7.2 ± 1.1 vs 5.7 ± 0.8; P < .001). No major complication was observed in either group. Cardiovascular and Interventional Radiological Society of Europe (CIRSE) grade 1 complications occurred in 5 of 21 patients in the BPF group and 7 of 30 patients in the polidocanol foam group, CIRSE grade 2 complications occurred in 5 of 21 patients in the BPF group and 4 of 30 patients in the polidocanol foam group; there were no significant differences between the two groups. CONCLUSIONS: BPF is a safe and effective sclerosant for VMs, showing better efficacy and similar safety as commonly used mild sclerosants. It could be a promising agent to treat VMs or other slow-flow vascular malformations.


Assuntos
Bleomicina , Malformações Vasculares , Masculino , Feminino , Humanos , Adulto , Polidocanol , Bleomicina/efeitos adversos , Estudos Retrospectivos , Soluções Esclerosantes , Escleroterapia/efeitos adversos , Escleroterapia/métodos , Malformações Vasculares/diagnóstico por imagem , Malformações Vasculares/terapia , Resultado do Tratamento
10.
Int J Low Extrem Wounds ; 22(1): 168-173, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33527869

RESUMO

Parkes-Weber syndrome (PWS) is a rare congenital vascular syndrome consisting of capillary, venous, lymphatic, and arteriovenous malformation. There are many complications of PWS, such as ulceration, bleeding, infection, and cardiac failure. Among them, skin ulceration is one of the thorniest problems in PWS, requiring multidisciplinary approaches for the management. In this article, we presented the case of an elderly patient with refractory ulceration who received numerous treatments with no effect and finally underwent a major amputation to improve the quality of life. Moreover, we reviewed 23 previously reported cases to improve our understanding of the management for PWS patients with ulceration.


Assuntos
Malformações Arteriovenosas , Síndrome de Klippel-Trenaunay-Weber , Síndrome de Sturge-Weber , Humanos , Idoso , Síndrome de Sturge-Weber/complicações , Síndrome de Sturge-Weber/diagnóstico , Síndrome de Sturge-Weber/cirurgia , Qualidade de Vida , Síndrome de Klippel-Trenaunay-Weber/complicações , Malformações Arteriovenosas/complicações , Malformações Arteriovenosas/diagnóstico , Malformações Arteriovenosas/cirurgia , Amputação Cirúrgica
11.
Front Immunol ; 13: 1042751, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36582224

RESUMO

Introduction: Immune-mediated inflammatory diseases (IMIDs) have been associated with an increased risk of venous thromboembolism (VTE) in multiple observational studies. However, a direct causally relation between IMIDs and VTE remains unclear to date. Here, we used Mendelian randomization (MR) analysis to investigate causal associations between IMIDs and VTE. Methods: We collected genetic data from published genome-wide association studies (GWAS) for six common IMIDs, specifically inflammatory bowel disease (IBD), Crohn's disease (CD), ulcerative colitis (UC), rheumatoid arthritis (RA), psoriasis (PSO), and systemic lupus erythematosus (SLE); and summary-level data for VTE, pulmonary embolism (PE), and deep vein thrombosis (DVT) from the FinnGen database. Two-sample MR analysis using inverse variance weighting (IVW) was performed to identify causal associations between IMIDs and VTE/DVT/PE, and sensitivity analyses were implemented for robustness. Results: IVW analysis showed a causal relationship between genetically predicted UC (one type of IBD) and the risk of VTE (OR = 1.043, 95% CI: 1.013-1.073, p = 0.004) and DVT (OR = 1.088, 95% CI: 1.043-1.136, p < 0.001), but we found no evidence of causality between UC and PE (OR = 1.029, 95% CI: 0.986-1.074, p = 0.19). In addition, no associations were observed between total IBD, CD, RA, SLE, or PSO and VTE/DVT/PE. Sensitivity analysis found no evidence for horizontal pleiotropy. Conclusion: This MR study provides new genetic evidence for the causal relationship between IMIDs and the risk of VTE. Our findings highlight the importance of active intervention and monitoring to mitigate VTE risk in patients with IBD, in particular those presenting with UC.


Assuntos
Artrite Reumatoide , Colite Ulcerativa , Doença de Crohn , Doenças Inflamatórias Intestinais , Lúpus Eritematoso Sistêmico , Embolia Pulmonar , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Agentes de Imunomodulação , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/complicações , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/genética , Colite Ulcerativa/genética , Colite Ulcerativa/complicações , Doença de Crohn/genética , Doença de Crohn/complicações , Artrite Reumatoide/etiologia , Lúpus Eritematoso Sistêmico/genética
12.
Med Sci Monit ; 28: e937878, 2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36324246

RESUMO

BACKGROUND We aimed to evaluate the association between postoperative nadir hematocrit (Hct) and severe acute kidney injury (AKI) in patients undergoing off-pump coronary artery bypass graft (OPCABG) surgery. MATERIAL AND METHODS Data of patients who received OPCABG were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. A generalized additive model was applied to explore the relationship between nadir Hct and severe AKI. Patients were divided into 4 groups by quartiles of postoperative nadir Hct, with the lowest group (Hct <25%) as reference. We conducted multivariate logistic regression models to calculate adjusted odds ratios (OR) and 95% CI and evaluate trend among the 4 groups. RESULTS In total, 1783 OPCABG patients were included. A nonlinear association between nadir Hct and severe AKI was identified. After adjusting for potential confounders, nadir Hct was negatively associated with risk of severe AKI when Hct was less than 31%; there was no statistical significance between highest Hct group (Hct ≥31%) and control group (Hct <25%; P>0.05). Tests for trend were significant (P<0.05). Subgroup analyses showed each 1% increase in postoperative nadir Hct was associated with a 23% decrease in risk of severe AKI (OR, 0.77; P=0.002) in lower BMI group (<30 kg/m²). CONCLUSIONS The association between postoperative nadir Hct and severe AKI in patients after OPCABG was nonlinear. Lower nadir Hct may be associated with increased risk of severe AKI when Hct values are less than 31%. However, no statistical significance was found between the highest Hct group and control group.


Assuntos
Injúria Renal Aguda , Ponte de Artéria Coronária sem Circulação Extracorpórea , Humanos , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Hematócrito , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Injúria Renal Aguda/etiologia , Cuidados Críticos , Fatores de Risco
13.
Biomed Res Int ; 2022: 5610317, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36345357

RESUMO

Background: The present study is aimed at identifying the differentially expressed genes (DEGs) and relevant biological processes and pathways associated with epicardial adipose tissue (EAT) from patients with coronary artery disease (CAD). We also explored potential biomarkers using two machine-learning algorithms and calculated the immune cell infiltration in EAT. Materials and Methods: Three datasets (GSE120774, GSE64554, and GSE24425) were obtained from the Gene Expression Omnibus (GEO) database. The GSE120774 dataset was used to evaluate DEGs between EAT of CAD patients and the control group. Functional enrichment analyses were conducted to study associated biological functions and mechanisms using the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Gene Set Enrichment Analysis (GSEA). After this, the least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) were performed to identify the feature genes related to CAD. The expression level of the feature genes was validated in GSE64554 and GSE24425. Finally, we calculated the immune cell infiltration and evaluated the correlation between the feature genes and immune cells using CIBERSORT. Results: We identified a total of 130 upregulated and 107 downregulated genes in GSE120774. Functional enrichment analysis revealed that DEGs are associated with several pathways, including the calcium signaling pathway, complement and coagulation cascades, ferroptosis, fluid shear stress and atherosclerosis, lipid and atherosclerosis, and regulation of lipolysis in adipocytes. TCF21, CDH19, XG, and NNAT were identified as feature genes and validated in the GSE64554 and GSE24425 datasets. Immune cell infiltration analysis showed plasma cells are significantly more numerous in EAT than in the control group (p = 0.001), whereas macrophage M0 (p = 0.024) and resting mast cells (p = 0.036) were significantly less numerous. TCF21, CDH19, XG, and NNAT were correlated with immune cells, including plasma cells, M0 macrophages, and resting mast cells. Conclusion: TCF21, CDH19, XG, and NNAT might serve as feature genes for CAD, providing new insights for future research on the pathogenesis of cardiovascular diseases.


Assuntos
Aterosclerose , Doença da Artéria Coronariana , Humanos , Doença da Artéria Coronariana/genética , Ontologia Genética , Biomarcadores/metabolismo , Tecido Adiposo/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos
14.
J Vasc Access ; : 11297298221096520, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35578550

RESUMO

BACKGROUND: Tunneled central venous catheters (tCVC) exchange may be difficult in some situations. We retrospectively report our preliminary experience of a novel extra-catheter guide wire technique for exchange of dysfunctional tCVC. MATERIALS AND METHODS: Retrospectively analyze the demographics, treatment details and outcomes data of 39 patients received tCVC exchange from January 2018 to January 2019. According to whether guide wire could pass through the catheter lumen, patients were divided into in-catheter group and extra-catheter group. The technical successful rate, peri-operative complications, 1-month and 6-month catheter flow rate was recorded and compared between the 2 groups. RESULTS: The final study population consists of 39 patients, including 16 in-catheter group and 23 extra-catheter group. The technical successful rate was 100% in both groups. All patients achieved restoration of line patency and completed at least 1 hemodialysis section. The 1-month (267.69 ± 20.12 vs. 274.13 ± 17.69, p = 0.604) and 6-month (255.81 ± 12.93 vs. 256.97 ± 11.20, p = 0.403) catheter flow rate was comparable between the 2 groups. CONCLUSION: The novel extra-catheter guide wire technique was helpful for in situ exchange of dysfunctional tunneled central venous hemodialysis catheters, especially when the guide wire could not pass through the catheter lumen.

15.
iScience ; 25(1): 103720, 2022 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-35005526

RESUMO

It is unknown whether antibody-mediated enhancement (ADE) contributes to the pathogenesis of COVID-19, and the conditions for ADE needs to be elucidated. We demonstrated that without inducing an ACE2-independent ADE on Raji cells, the neutralizing antibody CB6, a mouse anti-S1 serum and convalescent plasma, induced ADE on cells expressing FcγRIIA/CD32A and low levels of endogenous ACE2. ADE occurred at sub-neutralizing antibody concentrations, indicating that unneutralized S protein was required for ADE. The enhanced infectivity of 614G variant was higher than that of 614D wildtype in the presence of antibodies, further suggesting that ADE may be influenced by virus strains with different ACE2-binding affinity. Finally, knockdown of ACE2 or treatment with a fusion-inhibition peptide EK1C4 significantly reduced ADE. In conclusion, we identified an ADE mechanism mediated by neutralizing antibodies against SARS-CoV-2. ACE2 may act as a secondary receptor required for the antibody- and FcγR-mediated enhanced entry of SARS-CoV-2.

16.
J Cell Physiol ; 237(1): 789-803, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34368954

RESUMO

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by proliferative vascular remodeling. Abnormal vascular smooth muscle cell (VSMC) phenotype switching is crucial to this process, highlighting the need for VSMC metabolic changes to cover cellular energy demand in CTEPH. We report that elevated Wnt family member 5B (WNT5B) expression is associated with vascular remodeling and promotes VSMC phenotype switching via mitochondrial dynamics regulation in CTEPH. Using primary culture of pulmonary artery smooth muscle cells, we show that high WNT5B expression activates VSMC proliferation and migration and results in mitochondrial fission via noncanonical Wnt signaling in CTEPH. Abnormal VSMC proliferation and migration were abolished by mitochondrial division inhibitor 1, an inhibitor of mitochondrial fission. Secreted frizzled-related protein 2, a soluble scavenger of Wnt signaling, attenuates VSMC proliferation and migration by accelerating mitochondrial fusion. These findings indicate that WNT5B is an essential regulator of mitochondrial dynamics, contributing to VSMC phenotype switching in CTEPH.


Assuntos
Hipertensão Pulmonar , Músculo Liso Vascular , Desdiferenciação Celular , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Células Cultivadas , Humanos , Hipertensão Pulmonar/metabolismo , Dinâmica Mitocondrial/fisiologia , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/metabolismo , Remodelação Vascular/genética , Proteínas Wnt/metabolismo
17.
Vascular ; 30(2): 349-356, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33878955

RESUMO

BACKGROUND: The endovascular technique of mechanochemical ablation (MOCA) has become popular in treating patients with saphenous reflux. We reported the histopathological findings in human ex-vivo incompetent great saphenous veins following treatment with saline, polidocanol, mechanical ablation and MOCA using ClariVein device. METHODS: Twenty-four vein GSV specimens were obtained via traditional surgery and treated with four methods: Group A: 0.9% normal saline (NS); Group B: 3% polidocanol; Group C: mechanical ablation + 0.9% NS; Group D: mechanical ablation + 3% polidocanol (MOCA). Hematoxylin and eosin (HE), Masson's trichrome and immunohistochemical staining were performed on each specimen and integrated optical densities were measured with vWF and a-SMA stains and statistically evaluated. vWF staining was used to assess endothelial damage and a a-SMA staining was used to assess media injury. RESULTS: HE and Masson's trichrome staining of Groups C and D revealed severe damage to the endothelium and media compared to Groups A and B. The statistical result of vWF staining showed the damage of endothelium was significantly increased by Group D compared to Groups A, B and C. The statistical result of a-SMA staining showed the damage of media was significantly increased by Groups C and D compared to Groups A and B. CONCLUSIONS: The mechanism of MOCA was caused by both endothelium damage and media tearing. The damage of endothelium was significantly increased by MOCA when compared with mechanical ablation alone.


Assuntos
Técnicas de Ablação , Varizes , Insuficiência Venosa , Técnicas de Ablação/efeitos adversos , Humanos , Polidocanol , Veia Safena/diagnóstico por imagem , Veia Safena/patologia , Veia Safena/cirurgia , Escleroterapia/efeitos adversos , Resultado do Tratamento , Varizes/diagnóstico por imagem , Varizes/cirurgia , Insuficiência Venosa/diagnóstico por imagem , Insuficiência Venosa/cirurgia
18.
Anal Chem ; 93(41): 13880-13885, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34628854

RESUMO

Dual-modal imaging systems could provide complementary information by taking advantage of each imaging modality. Herein, a fluorescence and 19F magnetic resonance imaging nanoprobe was developed through preparation of 19F-grafted fluorescent carbonized polymer dots (FCPDs). Both fluorescence and 19F nuclear magnetic resonance intensities of these FCPDs can be modulated by controlling the carbonization processes. The strong yellow fluorescence renders these FCPDs capable of cell fluorescence imaging. The in vitro and in vivo assessments demonstrated that the as-prepared FCPDs were suitable for 19F magnetic resonance imaging (19F MRI), which would provide great potential for biological imaging and early diagnosis applications. Moreover, this fabrication strategy offers a new protocol for 19F MRI nanoprobe design.


Assuntos
Pontos Quânticos , Corantes , Fluorescência , Imageamento por Ressonância Magnética , Polímeros
19.
J Cell Physiol ; 236(10): 7159-7175, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33755211

RESUMO

Atherosclerosis is a significant cardiovascular burden and a leading cause of death worldwide, recognized as a chronic sterile inflammatory disease. Pyroptosis is a novel proinflammatory regulated cell death, characterized by cell swelling, plasma membrane bubbling, and robust release of proinflammatory cytokines (such as interleukin IL-1ß and IL-18). Mounting studies have addressed the crucial contribution of pyroptosis to atherosclerosis and clarified the candidate therapeutic agents targeting pyroptosis for atherosclerosis. Herein, we review the initial characterization of pyroptosis, the detailed mechanisms of pyroptosis, current evidence about pyroptosis and atherosclerosis, and potential therapeutic strategies that target pyroptosis in the development of atherosclerosis.


Assuntos
Anti-Inflamatórios/uso terapêutico , Artérias/efeitos dos fármacos , Aterosclerose/tratamento farmacológico , Citocinas/metabolismo , Inflamassomos/metabolismo , Mediadores da Inflamação/metabolismo , Piroptose/efeitos dos fármacos , Animais , Artérias/metabolismo , Artérias/patologia , Aterosclerose/metabolismo , Aterosclerose/patologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/patologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Transdução de Sinais
20.
Ann Vasc Surg ; 69: 447.e1-447.e8, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32745655

RESUMO

Pulmonary sequestration is an uncommon congenital pulmonary anomaly associated with aberrant systemic arteries which usually originate from the thoracic aorta or abdominal aorta. Traditionally, surgical resection and ligation of the feeding vessels are the gold standard treatments of the disease. Endovascular intervention and hybrid operation are promising treatment options. However, the case reports with endovascular and hybrid treatment are sparse to our knowledge. We presented 2 symptomatic adult patients with pulmonary sequestration successfully treated by hybrid operation and transcatheter embolization, respectively. Besides, we reviewed 37 previously reported cases of pulmonary sequestration treated by endovascular or hybrid treatment.


Assuntos
Sequestro Broncopulmonar/terapia , Embolização Terapêutica , Procedimentos Endovasculares , Pneumonectomia , Adulto , Sequestro Broncopulmonar/diagnóstico por imagem , Terapia Combinada , Humanos , Resultado do Tratamento , Adulto Jovem
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