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1.
Eur Radiol ; 32(10): 7295-7306, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36048205

RESUMO

OBJECTIVE: To develop a quantitative Response Evaluation Criteria in Solid Tumors (qRECIST) for evaluating response to neoadjuvant therapy (nT) in ESCCs relying on multiparametric (mp) MRI. METHODS: Patients with cT2-T4a/N0-N3/M0 ESCC undergoing pre-nT and post-nT esophageal mpMRI before radical resection were prospectively included. Images were reviewed by two experienced radiologists. qRECIST was redefined using four methods including conventional criterion (cRECIST) and three model-dependent RECIST relying on quantitative MRI measurements at pre-nT, post-nT, and delta pre-post nT, respectively. Pathological tumor regression grades (TRGs) were used as a reference standard. The rates of agreement between four qRECIST methods and TRGs were determined with a Cronbach's alpha test, area under the curve (AUC), and a diagnostic odds ratio meta-analysis. RESULTS: Ninety-one patients were enrolled. All four methods revealed high inter-reader agreements between the two radiologists, with a Kappa coefficient of 0.96, 0.87, 0.88, and 0.97 for cRECIST, pre-nT RECIST, post-nT RECIST, and delta RECIST, respectively. Among them, delta RECIST achieved the highest overall agreement rate (67.0% [61/91]) with TRGs, followed by post-nT RECIST (63.8% [58/91]), cRECIST (61.5% [56/91]), and pre-nT RECIST (36.3% [33/91]). Especially, delta RECIST achieved the highest accuracy (97.8% [89/91]) in distinguishing responders from non-responders, with 97.3% (34/35) for responders and 98.2% (55/56) for non-responders. Post-nT RECIST achieved the highest accuracy (93.4% [85/91]) in distinguishing complete responders from non-pCRs, with 77.8% (11/18) for pCRs and 94.5% (69/73) for non-pCRs. CONCLUSION: The qRECIST with mpMRI can assess treatment-induced changes and may be used for early prediction of response to nT in ESCC patients. KEY POINTS: • Quantitative mpMRI can reliably assess tumor response, and delta RECIST model had the best performance in evaluating response to nT in ESCCs, with an AUC of 0.98, 0.95, 0.80, and 0.82 for predicting TRG0, TRG1, TRG2, and TRG3, respectively. • In distinguishing responders from non-responders, the rate of agreement between delta RECIST and pathology was 97.3% (34/35) for responders and 98.2% (55/56) for non-responders, resulting in an overall agreement rate of 97.8% (89/91). • In distinguishing pCRs from non-pCR, the rate of agreement between MRI and pathology was 77.8% (11/18) for pCRs and 94.5% (69/73) for non- pCRs, resulting in an overall agreement rate of 91.2% (83/91).


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Humanos , Terapia Neoadjuvante , Critérios de Avaliação de Resposta em Tumores Sólidos , Resultado do Tratamento
2.
Immunology ; 2022 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-36054617

RESUMO

Mast cells (MCs), central players in allergy and parasitic infections, play key roles in inflammation and fibrosis. Here, the impact of MCs on the progression of Coxsackievirus B3 (CVB3)-induced viral myocarditis (VMC) and fibrosis was investigated using MC-deficient KitW-sh mice. Viral titres, cellular infiltrates and heart pathologies were evaluated and compared with wild-type (WT) mice during acute CVB3 infection of C57BL/6 mice. CVB3 infection induced an increased accumulation and degranulation of MCs in the hearts of mice during acute infection. MC-deficient KitW-sh mice had slightly higher viral titres, decreased VMC and cardiac fibrosis and improved cardiac dysfunction compared to WT mice via decreasing cardiac influx of Ly6Chigh monocytes/macrophages (Mo/Mφ). While bone marrow-derived MC reconstitution decreased viral titre and worsened improved survival and VMC severity in Wsh mice. MC-fibroblasts co-culture revealed a cardiac MC-fibroblasts crosstalk during early infection: fibroblasts trigger MC degranulation and secretion of CCL2 and tumour necrosis factor alpha (TNF-α) via producing early stem cell factor (SCF); while MCs-fibrogenic mediators (TNF-α) stimulate fibroblasts to increase CCL2, α-smooth muscle actin (SMA), collagen and transforming growth factor beta(TGFß) expression, thus aggravating cardiac fibrosis. MCs and fibroblast-derived CCL2s are both essential for cardiac Ly6Chigh Mo/Mφ influx. Administration of recombinant mouse SCF to CVB3-infected mice aggravates VMC via accelerating MCs accumulation and cardiac influx of Ly6Chi Mo/Mφ. Collectively, our data highlight an early MC-fibroblast crosstalk and SCF/MC/CCL2/Mo/Mφ axis as important mechanisms required for triggering VMC and myocardial fibrosis. This finding indicates critical roles of MCs in initiating and modulating cardiac innate response to CVB3 and has an implication in developing new and more effective treatments for VMC.

3.
Front Cardiovasc Med ; 9: 945557, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35990936

RESUMO

Chronic inflammation is a key pathological process in atherosclerosis. RNA binding proteins (RBPs) have been reported to play an important role in atherosclerotic plaque formation, and they could regulate the expression of inflammatory factors by phosphorylation modification. Y-box binding protein 1 (YB1) is an RBP that has participated in many inflammatory diseases. Here, we found an increased expression of phosphorylated YB1 (pYB1) in atherosclerotic plaques and demonstrated that YB1 dephosphorylation reduced lipid accumulation and lesion area in the aorta in vivo. Additionally, we found that inflammatory cytokines were downregulated in the presence of YB1 dephosphorylation, particularly CCL2, which participates in the pathogenesis of atherosclerosis. Furthermore, we demonstrated that CCL2 mRNA rapid degradation was mediated by the glucocorticoid receptor-mediated mRNA decay (GMD) process during YB1 dephosphorylation, which resulted in the downregulation of CCL2 expression. In conclusion, YB1 phosphorylation affects the development of atherosclerosis through modulating inflammation, and targeting YB1 phosphorylation could be a potential strategy for the treatment of atherosclerosis by anti-inflammation.

4.
Harmful Algae ; 117: 102272, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35944959

RESUMO

In recent years, researches on microalgae inhibition with plant-derived active substances have attracted much attention. In this study, the inhibition of six plant-derived alkaloids (neferine, isoliensinine, linensinine, nuciferine, capsaicin, and hordenine) on bloom-forming cyanobacteria Microcystis aeruginosa were investigated. The results showed that neferine and nuciferine had stronger inhibition on the growth of M. aeruginosa compared with the other four alkaloids, and the relative inhibition rate reached 91.27% and 88.70% at the concentration of 4.5 mg/L after 7 d of exposure, respectively. Different from neferine, nuciferine has no inhibition on Chlorella sp. and Tetradesmus obliquus. It also increased the diversity and species homogeneity of phytoplankton in the environmental water samples. Nuciferine decreased the contents of chlorophyll a and ß-carotene in M. aeruginosa with the extension of treatment time, which was 59.40% and 31.90% of the control at the concentration of 1.04 mg/L after 48 h, respectively. After 48 h of nuciferine exposure, the values of fluorescence parameters including maximum quantum yield (Fv/Fm), actual quantum yield of PSII (Yield), non-photochemical quenching (qN and NPQ), and electron transport rates (ETR) of M. aeruginosa cells were significantly decreased and photosynthetic capacity was weakened. The superoxide dismutase (SOD), catalase (CAT), ascorbic acid (ASA), and glutathione (GSH) in the cells were significantly reduced, and the hydrogen peroxide (H2O2) and malonaldehyde (MDA) contents continued to accumulate, causing severe oxidative damage. Therefore, the good biological safety and strong specific inhibition of nuciferine makes it have great application prospects in the inhibition of cyanobacteria blooms.


Assuntos
Alcaloides , Chlorella , Cianobactérias , Microcystis , Alcaloides/farmacologia , Clorofila A , Peróxido de Hidrogênio
5.
Int J Surg Pathol ; : 10668969221117255, 2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36000286

RESUMO

Primary cylindroma of the breast is extremely rare. To the best of our knowledge, there have been only 18 tumors reported. All of them were benign and had no mitosis. However, the rarity of this entity made the correct diagnosis preoperatively very difficult. Here we present a unique cylindroma with focal brisk mitosis and largest diameter of 5cm in an 80-year woman, she was misdiagnosed as adenoid cystic carcinoma in biopsy and then underwent a radical breast resection. We reviewed the related literature and emphasized differential diagnosis.

6.
Abdom Radiol (NY) ; 47(10): 3394-3405, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35916943

RESUMO

PURPOSE: To investigate the efficacy of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the early prediction of the pathologic response to neoadjuvant chemotherapy (NAC) in patients with locally advanced gastric cancer (LAGC). METHODS: Fifty patients with LAGC who were treated with NAC followed by radical gastrectomy were enrolled. Uncontrasted and DCE-MRI were performed within 1 week before NAC. According to tumor regression grading (TRG), patients were labeled as responders (TRG = 0 + 1) and non-responders (TRG = 2 + 3). Apparent diffusion coefficients (ADC) and DCE-MRI kinetics (Ktrans, Ve, and Kep) were compared between the two groups. Logistic regression analysis was performed to screen independent factors to predict the NAC efficacy. The relationship between MRI parameters and TRG was studied by Spearman's correlation analysis. Receiver-operating characteristic curve analyses were applied to evaluate the efficacy. RESULTS: ADC, Ktrans, and Kep values were higher in responders than in non-responders (p < 0.05) and correlated with TRG (p < 0.05). The ADC and Kep values were independent markers for predicting TRG. The area under the curve, sensitivities, specificities of ADC, Ktrans, Kep, and ADC + Kep were 0.813, 0.699, 0.709, 0.886;73.64%, 65.54%, 63.21%, 70.37%; 86.47%, 54.97%, 79.47%, 95.65%; respectively. ADC + Kep demonstrated a higher efficacy than Ktrans and Kep (p = 0.012, 0.011), but without improvement compared with ADC (p > 0.05). CONCLUSION: Both DWI and DCE-MRI can effectively predict the pathologic response to NAC in LAGC. A combination of ADC and Kep increased the efficacy, and ADC is the most valuable imaging parameter.


Assuntos
Terapia Neoadjuvante , Neoplasias Gástricas , Meios de Contraste , Imagem de Difusão por Ressonância Magnética/métodos , Humanos , Imageamento por Ressonância Magnética/métodos , Terapia Neoadjuvante/métodos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia
7.
J Card Surg ; 37(10): 3426-3427, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35916149

RESUMO

A stented elephant trunk graft entrapped in the false lumen during Sun's procedure (total arch replacement combined with stented elephant trunk implantation) is a serious complication with an extremely high mortality rate. This article describes a case of a patient who was successfully saved with the use of thoracic endovascular aortic repair.


Assuntos
Aneurisma Dissecante , Aneurisma da Aorta Torácica , Implante de Prótese Vascular , Procedimentos Endovasculares , Aneurisma Dissecante/cirurgia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Prótese Vascular , Implante de Prótese Vascular/métodos , Procedimentos Endovasculares/métodos , Humanos , Stents , Resultado do Tratamento
8.
ESC Heart Fail ; 2022 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-35950517

RESUMO

AIMS: The present study aimed to evaluate the prognostic value of atrial strain and strain rate (SR) parameters derived from cardiac magnetic resonance (CMR) feature tracking (FT) in patients with ischaemic and non-ischaemic dilated cardiomyopathy with heart failure with reduced ejection fraction (HFrEF) but without atrial fibrillation. METHODS AND RESULTS: A total of 300 patients who underwent CMR with left ventricular ejection fraction (LVEF) ≤ 40% and ischaemic or non-ischaemic dilated cardiomyopathy were analysed in this retrospective study. Major adverse cardiac events (MACEs) include cardiovascular death, heart transplantation, and rehospitalization for worsening HF. Ninety-four patients had MACEs during median follow-up of 3.84 years. Multivariate Cox regression models adjusted for common clinical and CMR risk factors detected a significant association between LA-εs and MACE in ischaemic (HR = 0.94/%; P = 0.002), non-ischaemic dilated cardiomyopathy (HR = 0.88/%; P = 0.001), or all included patients (HR = 0.87; P < 0.001). LA-εs provided incremental prognostic value over conventional outcome predictors (Uno C statistical comparison model: from 0.776 to 0.801, P < 0.0001; net reclassification improvement: 0.075, 95% CI: 0.0262-0.1301). Kaplan-Meier analysis revealed that the risk of MACE occurrence increased significantly with lower tertiles of left atrial reservoir strain (LA-εs) (log-rank P < 0.0001). Patients in the worst LA-εs tertile faced a significantly increased risk of MACEs irrespective of late gadolinium enhancement (LGE) (log-rank P < 0.0001). CONCLUSIONS: LA-εs derived from CMR FT has a significant prognostic impact on patients with ischaemic or non-ischaemic dilated cardiomyopathy, incremental to common clinical and CMR risk-factors.

9.
Artigo em Inglês | MEDLINE | ID: mdl-35805252

RESUMO

Urban agglomerations are an important symbol in the development of modernization. In this paper, we utilize the National Urban Agglomeration (NUA) policy as a quasi-natural experiment in the Chinese context. Adopting data from 280 cities from 2005 to 2019 as research samples, we use difference-in-differences (DID) and spatial difference-in-differences models (SDID) to examine the effect and mechanism of the implementation of the NUA policy on economic development and environmental pollution in China. The result shows that the NUA policy can achieve urban economic and environmental gains, which still holds after the robustness test. The heterogeneity analysis showed that the effects of the NUA policy are more evident in large and medium-sized cities. The curbing effect of the NUA policy on pollution emissions is apparent in the eastern region. Considering spatial heterogeneity, the expected economic and environmental benefits of the NUA policy are partially borne out. In addition to the green technology innovation, the NUA policy also influences regional economic development and environmental pollution through industrial agglomeration and the upgrading of industrial structures, respectively. It is essential to strengthen regional cooperation and establish the development concept of community interests between cities.


Assuntos
Desenvolvimento Econômico , Poluição Ambiental , China , Cidades , Poluição Ambiental/análise , Políticas
11.
J Clin Med ; 11(15)2022 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-35893355

RESUMO

Type 2 diabetes mellitus (T2DM) is associated with a high prevalence of diastolic dysfunction and congestive heart failure. A potential contributing factor is the accelerated accumulation of diffuse myocardial fibrosis and stiffness. Novel cardiac magnetic resonance (CMR) imaging techniques can identify both myocardial fibrosis and contractility quantitatively. This study aimed to investigate the dynamic characteristics of the myocardial strain and altered extracellular volume (ECV) fraction as determined by 7.0 T CMR in T2DM mice. C57Bl/6J mice were randomly divided into T2DM (fed a high-fat diet) and control (fed a normal diet) groups. They were scanned on 7.0 T MRI every 4 weeks until the end of week 24. The CMR protocol included multi-slice cine imaging to assess left ventricle strain and strain rate, and pre- and post-contrast T1 mapping images to quantify ECV. The ECV in the T2DM mice was significantly higher (p < 0.05) than that in the control group since week 12 with significantly impaired myocardial strain (p < 0.05). A significant linear correlation was established between myocardial strain and ECV (p < 0.001) and left ventricular-ejection fraction and ECV (p = 0.003). The results suggested that CMR feature tracking-derived myocardial strain analysis can assess functional abnormalities that may be associated with ECM alterations in diabetic cardiomyopathy, contributing to the study of diabetic therapy effects.

12.
Plant Cell ; 2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35861414

RESUMO

Pollen tube guidance regulates the growth direction and ovule targeting of pollen tubes in pistils, which is crucial for the completion of sexual reproduction in flowering plants. The Arabidopsis (Arabidopsis thaliana) pollen-specific receptor kinase (PRK) family members PRK3 and PRK6 are specifically tip-localized and essential for pollen tube growth and guidance. However, the mechanisms controlling the polar localization of PRKs at the pollen tube tip are unclear. The Arabidopsis P4-ATPase ALA3 helps establish the polar localization of apical phosphatidylserine (PS) in pollen tubes. Here, we discovered that loss of ALA3 function caused pollen tube defects in growth and ovule targeting and significantly affected the polar localization pattern of PRK3 and PRK6. Both PRK3 and PRK6 contain two polybasic clusters in the intracellular juxtamembrane domain, and they bound to PS in vitro. PRK3 and PRK6 with polybasic cluster mutations showed reduced or abolished binding to PS and altered polar localization patterns, and they failed to effectively complement the pollen tube-related phenotypes of prk mutants. These results suggest that ALA3 influences the precise localization of PRK3, PRK6 and other PRKs by regulating the distribution of PS, which plays a key role in regulating pollen tube growth and guidance.

13.
J Evol Biol ; 2022 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-35895083

RESUMO

The evolution of sex chromosomes is hypothesized to be punctuated by consecutive recombination cessation events, forming "evolutionary strata" that ceased to recombine at different time points. The demarcation of evolutionary strata is often assessed by estimates of the timing of recombination cessation (tRC ) along the sex chromosomes, commonly inferred from the level of synonymous divergence or with species phylogenies at gametologous (X-Y or Z-W) sequence data. However, drift and selection affect sequences unpredictably and introduce uncertainty when inferring tRC . Here, we assess two alternative phylogenetic approaches to estimate tRC ; (i) the expected likelihood weight (ELW) approach that finds the most likely topology among a set of hypothetical topologies and (ii) the BEAST approach that estimates tRC with specified calibration priors on a reference species topology. By using Z and W gametologs of an old and a young evolutionary stratum on the neo-sex chromosome of Sylvioidea songbirds, we show that the ELW and BEAST approaches yield similar tRC estimates, and that both outperform two frequently applied approaches utilizing synonymous substitution rates (dS) and maximum likelihood (ML) trees, respectively. Moreover, we demonstrate that both ELW and BEAST provide more precise tRC estimates when sequences of multiple species are included in the analyses.

14.
J Hematol Oncol ; 15(1): 88, 2022 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-35799191

RESUMO

Relapsed or refractory (R/R) acute myeloid leukemia (AML) has a poor prognosis. In this study, we evaluated chimeric antigen receptor (CAR) T cell therapy targeting CLL-1 in adults with R/R AML patients. Patients received conditioning chemotherapy with cyclophosphamide (500 mg/m2) and fludarabine (30 mg/m2) for 3 days and an infusion of a dose of 1-2 × 106 CAR-T cells/kg. The incidence of dose-limiting toxicity was the primary endpoint. Ten patients were treated, and all developed cytokine release syndrome (CRS); 4 cases were low-grade, while the remaining 6 were considered high-grade CRS. No patient developed CAR-T cell-related encephalopathy syndrome (CRES). Severe pancytopenia occurred in all patients. Two patients died of severe infection due to chronic agranulocytosis. The complete response (CR)/CR with incomplete hematologic recovery (CRi) rate was 70% (n = 7/10). The median follow-up time was 173 days (15-488), and 6 patients were alive at the end of the last follow-up. CAR-T cells showed peak expansion within 2 weeks. Notably, CLL-1 is also highly expressed in normal granulocytes, so bridging hematopoietic stem cell transplantation (HSCT) may be a viable strategy to rescue long-term agranulocytosis due to off-target toxicity. In conclusion, this study is the first to demonstrate the positive efficacy and tolerable safety of CLL-1 CAR-T cell therapy in adult R/R AML.


Assuntos
Agranulocitose , Leucemia Linfocítica Crônica de Células B , Leucemia Mieloide Aguda , Adulto , Antígenos CD19 , Síndrome da Liberação de Citocina , Humanos , Imunoterapia Adotiva/efeitos adversos , Leucemia Mieloide Aguda/terapia , Linfócitos T
15.
Mol Ther ; 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35715953

RESUMO

The full potential of tumor-infiltrating lymphocyte (TIL) therapy has been hampered by the inadequate activation and low persistence of TILs, as well as inefficient neoantigen presentation by tumors. We transformed tumor cells into artificial antigen-presenting cells (aAPCs) by infecting them with a herpes simplex virus 1 (HSV-1)-based oncolytic virus encoding OX40L and IL12 (OV-OX40L/IL12) to provide local signals for optimum T cell activation. The infected tumor cells displayed increased expression of antigen-presenting cell-related markers and induced enhanced T cell activation and killing in coculture with TILs. Combining OV-OX40L/IL12 and TIL therapy induced complete tumor regression in patient-derived xenograft and syngeneic mouse tumor models and elicited an antitumor immunological memory. In addition, the combination therapy produced aAPC properties in tumor cells, activated T cells, and reprogrammed macrophages to a more M1-like phenotype in the tumor microenvironment. This combination strategy unleashes the full potential of TIL therapy and warrants further evaluation in clinical studies.

16.
Bioresour Technol ; 358: 127402, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35667534

RESUMO

The effects of adjusting the nitrogen-phosphorus (N/P) ratio of wastewater and indigenous bacteria on swine wastewater treatment by Chlorella sp. HL were investigated. The optimal N/P ratio of Chlorella in swine wastewater was 20 by adjusting the phosphorus concentration. The participation of indigenous bacteria increased total extracellular polymeric substances content, which was beneficial to maintain the stability of the algal-bacterial consortium, and improved the algal density and the removal rate of total nitrogen, total phosphorus, and chemical oxygen demand by 47.8%, 24.0%, 30.7%, and 326.7%, respectively. Proteobacteria was the dominant phylum with the relative abundance of 71.58% in the algal-bacterial system at optimal N/P ratio, and Brevundimonas, Chryseobacterium, and Pseudomonas played positive roles in the establishment of symbiotic systems at the genus level. These results provide a theoretical basis for the construction of an efficient algal-bacterial symbiotic system in swine wastewater treatment and support for commercial scale-up.


Assuntos
Chlorella , Microalgas , Animais , Bactérias , Nitrogênio , Fósforo , Suínos , Águas Residuárias/química
17.
Br J Haematol ; 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35594370

RESUMO

The delivery of bispecific antibodies (BsAbs) targeting B-cell maturation antigen (BCMA) and CD3 using the gene therapy approach is a promising alternative for BsAb administration in patients with multiple myeloma (MM). In the present study, we evaluated the efficacy of this approach using a xenograft model. Tumour growth was significantly delayed in mice treated with single electroporation-enhanced intramuscular injection of plasmid DNA encoding BCMA/CD3 BsAb in contrast to the vehicle control-treated group. Limited toxicity was observed following treatment. This study demonstrates that the gene therapy-based approach for the delivery of BCMA/CD3 BsAb is effective and safe for the treatment of MM.

18.
J Magn Reson Imaging ; 2022 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-35436040

RESUMO

BACKGROUND: Diffuse myocardial interstitial fibrosis (DMIF) is a key factor for heart failure (HF) in diabetic cardiomyopathy. MRI T1-mapping technique can quantitatively evaluate DMIF. PURPOSE: To evaluate of early DMIF in a type 1 diabetes mellitus (T1DM) mouse model through 7.0 T MRI T1 mapping. STUDY TYPE: Prospective. ANIMAL MODEL: A total of 50 8-week-old C57Bl/6J male mice were divided into control (n = 20) and T1DM (n = 30) groups. FIELD STRENGTH/SEQUENCE: A 7.0 T small animal MRI; gradient echo Look-Locker inversion recovery T1-mapping sequence; cine MRI. Scans were acquired in control and T1DM mice every 4 weeks until 24 weeks. ASSESSMENT: End-diastolic volume (EDV), end-systolic volume (ESV), ejection fraction (EF), left ventricle (LV) mass, fractional shortening (FS), and E/A ratio. They were evaluated through echocardiography and cine MRI. The extracellular volume fraction (ECV) was calculated. Sirius Red staining was performed and calculated collagen volume fraction (CVF). STATISTICAL TESTS: Differences in ECV and CVF between two groups were analyzed using one-way analysis of variance. The correlation between ECV and CVF was assessed using Pearson's correlations. RESULTS: Compared with the control group, a progressive decrease in FS, EF, and E/A ratio was observed in the T1DM group. Both ECV and CVF values gradually increased during diabetes progression. A significant increase in ECV and CVF values was observed at 12 weeks (ECV: 32.5% ± 1.6% vs. 28.1% ± 1.8%; CVF: 6.9% ± 1.8% vs. 3.3% ± 1.1%). ECV showed a strong correlation with CVF (r = 0.856). DATA CONCLUSION: ECV is an accurate and feasible imaging marker that can be used to quantitatively assess DMIF changes over time in T1DM mice. ECV has potential to accurately detect DMIF in the early stage and may be a useful imaging tool to assess the need for early intervention in T1DM mice. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 3.

19.
Eur Radiol ; 32(9): 5930-5942, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35384460

RESUMO

OBJECTIVES: To develop and validate an optimal model based on the 1-mm-isotropic-3D contrast-enhanced StarVIBE MRI sequence combined with clinical risk factors for predicting survival in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Patients with ESCC at our institution from 2015 to 2017 participated in this retrospective study based on prospectively acquired data, and were randomly assigned to training and validation groups at a ratio of 7:3. Random survival forest (RSF) and variable hunting methods were used to screen for radiomics features and LASSO-Cox regression analysis was used to build three models, including clinical only, radiomics only and combined clinical and radiomics models, which were evaluated by concordance index (CI) and calibration curve. Nomograms and decision curve analysis (DCA) were used to display intuitive prediction information. RESULTS: Seven radiomics features were selected from 434 patients, combined with clinical features that were statistically significant to construct the predictive models of disease-free survival (DFS) and overall survival (OS). The combined model showed the highest performance in both training and validation groups for predicting DFS ([CI], 0.714, 0.729) and OS ([CI], 0.730, 0.712). DCA showed that the net benefit of the combined model and of the clinical model is significantly greater than that of the radiomics model alone at different threshold probabilities. CONCLUSIONS: We demonstrated that a combined predictive model based on MR Rad-S and clinical risk factors had better predictive efficacy than the radiomics models alone for patients with ESCC. KEY POINTS: • Magnetic resonance-based radiomics features combined with clinical risk factors can predict survival in patients with ESCC. • The radiomics nomogram can be used clinically to predict patient recurrence, DFS, and OS. • Magnetic resonance imaging is highly reproducible in visualizing lesions and contouring the whole tumor.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Intervalo Livre de Doença , Neoplasias Esofágicas/diagnóstico por imagem , Carcinoma de Células Escamosas do Esôfago/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Nomogramas , Estudos Retrospectivos
20.
Cell Rep ; 39(5): 110770, 2022 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-35477022

RESUMO

The emergence of the SARS-CoV-2 Omicron variant is dominant in many countries worldwide. The high number of spike mutations is responsible for the broad immune evasion from existing vaccines and antibody drugs. To understand this, we first present the cryo-electron microscopy structure of ACE2-bound SARS-CoV-2 Omicron spike. Comparison to previous spike antibody structures explains how Omicron escapes these therapeutics. Secondly, we report structures of Omicron, Delta, and wild-type spikes bound to a patient-derived Fab antibody fragment (510A5), which provides direct evidence where antibody binding is greatly attenuated by the Omicron mutations, freeing spike to bind ACE2. Together with biochemical binding and 510A5 neutralization assays, our work establishes principles of binding required for neutralization and clearly illustrates how the mutations lead to antibody evasion yet retain strong ACE2 interactions. Structural information on spike with both bound and unbound antibodies collectively elucidates potential strategies for generation of therapeutic antibodies.


Assuntos
COVID-19 , SARS-CoV-2 , Enzima de Conversão de Angiotensina 2 , Anticorpos Neutralizantes , Anticorpos Antivirais , Microscopia Crioeletrônica , Humanos , Fragmentos Fab das Imunoglobulinas , Glicoproteína da Espícula de Coronavírus
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