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1.
Cell Death Dis ; 13(1): 40, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013137

RESUMO

Iron is vital for many physiological functions, including energy production, and dysregulated iron homeostasis underlies a number of pathologies. Ferroptosis is a recently recognized form of regulated cell death that is characterized by iron dependency and lipid peroxidation, and this process has been reported to be involved in multiple diseases. The mechanisms underlying ferroptosis are complex, and involve both well-described pathways (including the iron-induced Fenton reaction, impaired antioxidant capacity, and mitochondrial dysfunction) and novel interactions linked to cellular energy production. In this review, we examine the contribution of iron to diverse metabolic activities and their relationship to ferroptosis. There is an emphasis on the role of iron in driving energy production and its link to ferroptosis under both physiological and pathological conditions. In conclusion, excess reactive oxygen species production driven by disordered iron metabolism, which induces Fenton reaction and/or impairs mitochondrial function and energy metabolism, is a key inducer of ferroptosis.

2.
Nucl Med Commun ; 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34864811

RESUMO

OBJECTIVE: This study explored the utility of oral vitamin C in reducing radiation accumulation in the salivary glands during total-body dynamic PET/computed tomography (CT) imaging with 68Ga labeled Prostate-specific membrane antigen (68Ga-PSMA-11). METHODS: We enrolled 31 patients who underwent total-body dynamic PET/CT imaging with 68Ga-PSMA-11, of which 11 were given oral vitamin C 30 min after starting the dynamic PET acquisition, whereas the others did not. The volume of interest was automatically segmented on the parotid and submandibular salivary glands once the PET acquisition was completed. The standard uptake value (SUV)mean and its slope during 30-60 min of the acquisition were compared between the trial and control groups. RESULTS: The SUVmean of the left and right parotid and submandibular glands in the trial group were 15.37 ± 3.07, 15.03 ± 2.64, 14.92 ± 4.38 and 15.38 ± 4.18, respectively. The respective values of the control group were 19.37 ± 3.82, 20.08 ± 3.55, 22.61 ± 5.62 and 22.73 ± 5.90. The SUVmean slope during 30-60 min of acquisition for the left and right parotid and submandibular glands in the trial group were 0.63 ± 0.13, 0.64 ± 0.14, 0.56 ± 0.25 and 0.62 ± 0.26, respectively. The respective values of the control group were 0.84 ± 0.21, 0.84 ± 0.17, 1.01 ± 0.34 and 1.02 ± 0.37. CONCLUSION: Oral vitamin C could reduce the accumulation of radiation in the salivary glands during 68Ga-PSMA-11 total-body dynamic PET/CT imaging.

3.
N Engl J Med ; 2021 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-34937145

RESUMO

BACKGROUND: Remdesivir improves clinical outcomes in patients hospitalized with moderate-to-severe coronavirus disease 2019 (Covid-19). Whether the use of remdesivir in symptomatic, nonhospitalized patients with Covid-19 who are at high risk for disease progression prevents hospitalization is uncertain. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving nonhospitalized patients with Covid-19 who had symptom onset within the previous 7 days and who had at least one risk factor for disease progression (age ≥60 years, obesity, or certain coexisting medical conditions). Patients were randomly assigned to receive intravenous remdesivir (200 mg on day 1 and 100 mg on days 2 and 3) or placebo. The primary efficacy end point was a composite of Covid-19-related hospitalization or death from any cause by day 28. The primary safety end point was any adverse event. A secondary end point was a composite of a Covid-19-related medically attended visit or death from any cause by day 28. RESULTS: A total of 562 patients who underwent randomization and received at least one dose of remdesivir or placebo were included in the analyses: 279 patients in the remdesivir group and 283 in the placebo group. The mean age was 50 years, 47.9% of the patients were women, and 41.8% were Hispanic or Latinx. The most common coexisting conditions were diabetes mellitus (61.6%), obesity (55.2%), and hypertension (47.7%). Covid-19-related hospitalization or death from any cause occurred in 2 patients (0.7%) in the remdesivir group and in 15 (5.3%) in the placebo group (hazard ratio, 0.13; 95% confidence interval [CI], 0.03 to 0.59; P = 0.008). A total of 4 of 246 patients (1.6%) in the remdesivir group and 21 of 252 (8.3%) in the placebo group had a Covid-19-related medically attended visit by day 28 (hazard ratio, 0.19; 95% CI, 0.07 to 0.56). No patients had died by day 28. Adverse events occurred in 42.3% of the patients in the remdesivir group and in 46.3% of those in the placebo group. CONCLUSIONS: Among nonhospitalized patients who were at high risk for Covid-19 progression, a 3-day course of remdesivir had an acceptable safety profile and resulted in an 87% lower risk of hospitalization or death than placebo. (Funded by Gilead Sciences; PINETREE ClinicalTrials.gov number, NCT04501952; EudraCT number, 2020-003510-12.).

4.
Clin Cosmet Investig Dermatol ; 14: 1629-1636, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34803388

RESUMO

Purpose: Monocyte subsets, including classical, intermediate and non-classical monocytes, are involved in the pathogenesis of inflammatory or autoimmune diseases. The pathogenic role of monocytes in the peripheral blood mononuclear cells (PBMCs) of patients with rosacea remains unclear. This study aimed to assess frequencies of monocyte subsets in PBMCs from rosacea patients before and after clinical treatment. Patients and Methods: We applied flow cytometry to examine frequencies of monocyte subsets in 116 patients with rosacea, while patients with 26 systemic lupus erythematosus (SLE), 28 acne and 42 normal healthy subjects without skin problems (HC) were recruited as controls. Expression of C-C chemokine receptor 2 (CCR2) on monocytes and plasma levels of CC-chemokine ligand 2 (CCL2), high mobility group box-1 (HMGB-1), interleukin-1 beta (IL-1ß) and tumor necrosis factor alpha (TNF-α) were measured in HC and rosacea patients before and after treatment. Results: The frequency of classical monocytes, but not intermediate or non-classical monocytes, was higher in rosacea as compared with HC, which decreased after treatment. Frequencies of monocyte subsets showed no gender difference, while increased with age in patients but not in HC. Frequencies of classical monocytes in patients with erythematotelangiectatic rosacea (ETR) and ETR-papulopustular rosacea (PPR) overlap were significantly higher than HC or patients with only PPR or phymatous rosacea (PhR). There was a significant higher expression of CCR2 in classical monocytes, with higher plasma levels of CCL2, HMGB-1, IL-1ß and TNF-α in patients than in HC, which all significantly decreased after treatment. Conclusion: Our data indicated a possible association between abnormal classical monocytes frequencies and rosacea.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34733343

RESUMO

Objectives: To systematically collate, appraise, and synthesize the current evidence on the Xuebijing injection (XBJI) for sepsis. Methods: Eight databases were searched for systematic reviews (SRs) or meta-analyses (MAs) on XBJI for sepsis. Assessing the Methodological Quality of Systematic Reviews-2 (AMSTAR-2), Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA), and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methods were used to assess the methodological quality, reporting quality, and evidence quality of the enrolled studies, respectively. Results: Out of the 13 studies that were included, all studies were rated critically low quality based on AMSTAR-2 results. Based on the results obtained from PRISMA, all studies were reported to be over 80%, while the GRADE system yielded three outcome measures rated high-quality, 16 were of moderate quality, and the rest were of low or critically low quality. Conclusions: The combination of XBJI and Western medicine (WM) showed significant synergy for the treatment of sepsis compared to WM alone. However, this conclusion should be treated with caution since the quality of the SRs/MAs providing the evidence was relatively low.

7.
J Nucl Med ; 2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34593593

RESUMO

The present study aimed to evaluate the feasibility of ultra-low 18F-fluorodeoxyglucose (FDG) activity in total-body positron emission tomography (PET)/computed tomography (CT) oncological studies. Methods: Thirty patients with cancer were enrolled prospectively and underwent a total-body PET/CT examination with an ultra-low 18F-FDG activity (0.37 MBq/kg) after an uptake time of 60 minutes. Among the enrolled patients, 11 were diagnosed with colorectal cancer (CRC). PET raw data were acquired within 15 minutes and reconstructed using data from the first 1, 2, 4, 8, 10 and the entire 15 min (G1, G2, G4, G8, G10, G15). Image quality was assessed qualitatively by two readers using a 5-point Likert scale twice. Cohen's kappa test was performed to investigate the intra-reader and inter-reader agreement. The standard uptake value (SUV)max of lesions, SUVmax, SUVmean, and standard deviation (SD) of the livers, the tumor-to-background ratio (TBR), and the signal-to-noise ratio (SNR) were measured and compared. The acquisition time for a clinically acceptable image quality was determined using an ultra low activity injection. In a matched-pair study, 11 patients with CRC who received a full FDG activity (3.7 MBq/kg) with a 2-min PET acquisition were selected retrospectively with matched sex, height, weight, body mass index, glucose level, uptake time, and pathological types with the 11 CRC subjects in the prospective study. Qualitative and quantitative analyses were performed and compared between the 11 patients with CRC in the ultra-low activity group and their matched full activity controls. Results: Qualitative analysis of image quality showed good intra- and inter-reader agreements (all kappa > 0.7). All the images acquired for 8-min or longer scored over 3 (indicating clinical acceptability). There was no significant difference in TBR and liver SNR among all the images acquired for 8-min or longer. In the matched study, no significant difference was found in the image quality score and quantitative parameters between the ultra-low activity group with an 8-min acquisition and the full activity group with a 2-min acquisition. Conclusion: Ultra-low FDG activity injection with 8-min acquisition in a total-body PET/CT study can achieve acceptable image quality equivalent to that in the full activity group using 2-min acquisition.

8.
Front Cell Dev Biol ; 9: 710461, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513840

RESUMO

Background: Differentiation between cerebral glioblastoma multiforme (GBM) and solitary brain metastasis (MET) is important. The existing radiomic differentiation method ignores the clinical and routine magnetic resonance imaging (MRI) features. Purpose: To differentiate between GBM and MET and between METs from the lungs (MET-lung) and other sites (MET-other) through clinical and routine MRI, and radiomics analyses. Methods and Materials: A total of 350 patients were collected from two institutions, including 182 patients with GBM and 168 patients with MET, which were all proven by pathology. The ROI of the tumor was obtained on axial postcontrast MRI which was performed before operation. Seven radiomic feature selection methods and four classification algorithms constituted 28 classifiers in two classification strategies, with the best classifier serving as the final radiomics model. The clinical and combination models were constructed using the nomograms developed. The performance of the nomograms was evaluated in terms of calibration, discrimination, and clinical usefulness. Student's t-test or the chi-square test was used to assess the differences in the clinical and radiological characteristics between the training and internal validation cohorts. Receiver operating characteristic curve analysis was performed to assess the performance of developed models with the area under the curve (AUC). Results: The classifier fisher_decision tree (fisher_DT) showed the best performance (AUC: 0.696, 95% CI:0.608-0.783) for distinguishing between GBM and MET in internal validation cohorts; the classifier reliefF_random forest (reliefF_RF) showed the best performance (AUC: 0.759, 95% CI: 0.613-0.904) for distinguishing between MET-lung and MET-other in internal validation cohorts. The combination models incorporating the radiomics signature and clinical-radiological characteristics were superior to the clinical-radiological models in the two classification strategies (AUC: 0.764 for differentiation between GBM in internal validation cohorts and MET and 0.759 or differentiation between MET-lung and MET-other in internal validation cohorts). The nomograms showed satisfactory performance and calibration and were considered clinically useful, as revealed in the decision curve analysis. Data Conclusion: The combination of radiomic and non-radiomic features is helpful for the differentiation among GBM, MET-lung, and MET-other.

9.
Front Oncol ; 11: 699789, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34490097

RESUMO

Objective: To identify optimal machine-learning methods for the radiomics-based differentiation of gliosarcoma (GSM) from glioblastoma (GBM). Materials and Methods: This retrospective study analyzed cerebral magnetic resonance imaging (MRI) data of 83 patients with pathologically diagnosed GSM (58 men, 25 women; mean age, 50.5 ± 12.9 years; range, 16-77 years) and 100 patients with GBM (58 men, 42 women; mean age, 53.4 ± 14.1 years; range, 12-77 years) and divided them into a training and validation set randomly. Radiomics features were extracted from the tumor mass and peritumoral edema. Three feature selection and classification methods were evaluated in terms of their performance in distinguishing GSM and GBM: the least absolute shrinkage and selection operator (LASSO), Relief, and Random Forest (RF); and adaboost classifier (Ada), support vector machine (SVM), and RF; respectively. The area under the receiver operating characteristic curve (AUC) and accuracy (ACC) of each method were analyzed. Results: Based on tumor mass features, the selection method LASSO + classifier SVM was found to feature the highest AUC (0.85) and ACC (0.77) in the validation set, followed by Relief + RF (AUC = 0.84, ACC = 0.72) and LASSO + RF (AUC = 0.82, ACC = 0.75). Based on peritumoral edema features, Relief + SVM was found to have the highest AUC (0.78) and ACC (0.73) in the validation set. Regardless of the method, tumor mass features significantly outperformed peritumoral edema features in the differentiation of GSM from GBM (P < 0.05). Furthermore, the sensitivity, specificity, and accuracy of the best radiomics model were superior to those obtained by the neuroradiologists. Conclusion: Our radiomics study identified the selection method LASSO combined with the classifier SVM as the optimal method for differentiating GSM from GBM based on tumor mass features.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34462790

RESUMO

PURPOSE: This study was to evaluate the effects of an ultra-low dose of [18F]-FDG on the image quality of total-body PET/CT and its lesion detectability in colorectal cancer (CRC). METHODS: Sixty-two CRC patients who underwent total-body PET/CT (uEXPLORER, United Imaging Healthcare, Shanghai, China) with an ultra-low dose (0.37 MBq/kg) of [18F]-FDG were enrolled in this retrospective study. The PET images were reconstructed with the entire 15-min dataset first and then split into 13-, 8-, 5-, 4-, 3-, 2-, and 1-min duration groups to simulate fast scanning images. For simplicity, the images reconstructed with the data from 15 to 1 min were referred to as G15, G13, and so on until G1. Subjective image quality was assessed with 5-point Likert scales. The objective image quality parameters included the SUVmax, SUVmean, and signal-to-noise ratio (SNR) of the liver and blood pool and the SUVmax and tumor-to-background ratio (TBR) of the lesions. G15 served as the control to evaluate lesion detectability. RESULTS: A total of 62 patients (43 men, 19 women; age 41-88, mean ± SD 64.0 ± 10.9 years) with 64 CRC primary tumor lesions and 10 low-grade intraepithelial neoplasia (LGIN) lesions were enrolled in this study. The subjective scores were highest for G15 (4.5 ± 0.5) and then decreased from G13 (4.3 ± 0.4) to G8 (3.7 ± 0.5). The liver SNR increased with the extension of acquisition time from G8 (17.2 ± 2.8) to G13 (20.6 ± 3.4) and G15 (21.9 ± 3.4). The liver SNR of G8 was not significantly different from that of G13 (p = 0.15) and was significantly different from that of G15 (p = 0.001). All 64 CRC lesions could be identified in all image groups, even on G1. One of ten LGINs was missed on G1, G2, and G3, and one LGIN was missed on G1, G2, G3, and G4. G15 served as the control, and 100% (48/48) lymph nodes could be found on G13 and G8 compared to 93.8% (45/48) lymph nodes on G5 and G4, 85.4% (41/48) lymph nodes on G3, 81.3% (39/48) lymph nodes on G2, and 77.1% (37/48) lymph nodes on G1. For liver metastases, there were no missed liver lesions on G13 and G8 and 3, 4, 6, 7, and 9 missed liver lesions on G5, G4, G3, G2, and G1, respectively. For other areas of metastasis, including the lung, peritoneum, and ovaries, there were no missed lesions in any group. CONCLUSIONS: Total-body PET/CT with an ultra-low dose of [18F]-FDG can maintain satisfactory image quality and lesion detectability in CRC.

11.
EJNMMI Phys ; 8(1): 51, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34264416

RESUMO

PURPOSE: A 2-m axial field-of-view, total-body PET/CT scanner (uEXPLORER) has been recently developed to provide total-body coverage and ultra-high sensitivity, which together, enables opportunities for in vivo time-activity curve (TAC) measurement of all investigated organs simultaneously with high temporal resolution. This study aims at quantifying the cumulated activity and patient dose of 2-[F-18]fluoro-2-deoxy-D-glucose (F-18 FDG ) imaging by using delayed time-activity curves (TACs), measured out to 8-h post-injection, for different organs so that the comparison between quantifying approaches using short-time method (up to 75 min post-injection) or long-time method (up to 8 h post-injection) could be performed. METHODS: Organ TACs of 10 healthy volunteers were collected using total-body PET/CT in 4 periods after the intravenous injection of F-18 FDG. The 8-h post-injection TACs of 6 source organs were fitted using a spline method (based on Origin (version 8.1)). To compare with cumulated activity estimated from spline-fitted curves, the cumulated activity estimated from multi-exponential curve was also calculated. Exponential curve was fitted with shorter series of data consistent with clinical procedure and previous dosimetry works. An 8-h dynamic bladder wall dose model considering 2 voiding were employed to illustrate the differences in bladder wall dose caused by the different measurement durations. Organ absorbed doses were further estimated using Medical Internal Radiation Dose (MIRD) method and voxel phantoms. RESULTS: A short-time measurement could lead to significant bias in estimated cumulated activity for liver compared with long-time-measured spline fitted method, and the differences of cumulated activity were 18.38% on average. For the myocardium, the estimated cumulated activity difference was not statistically significant due to large variation in metabolism among individuals. The average residence time differences of brain, heart, kidney, liver, and lungs were 8.38%, 15.13%, 25.02%, 23.94%, and 16.50% between short-time and long-time methods. Regarding effective dose, the maximum differences of residence time between long-time-measured spline fitted curve and short-time-measured multi-exponential fitted curve was 9.93%. When using spline method, the bladder revealed the most difference in the effective dose among all the investigated organs with a bias up to 21.18%. The bladder wall dose calculated using a long-time dynamic model was 13.79% larger than the two-voiding dynamic model, and at least 50.17% lower than previous studies based on fixed bladder content volume. CONCLUSIONS: Long-time measurement of multi-organ TACs with high temporal resolution enabled by a total-body PET/CT demonstrated that the clinical procedure with 20 min PET scan at 1 h after injection could be used for retrospective dosimetry analysis in most organs. As the bladder content contributed the most to the effective dose, a long-time dynamic model was recommended for the bladder wall dose estimation.

12.
Front Pharmacol ; 12: 689092, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220514

RESUMO

Hyperlipidemia is a chronic disorder that is difficult to cure and usually treated with long-term lipid-reducing drugs. Recent trends have led to the use of diet therapies or food-derived strategies in the treatment of such long-term diseases. The Chinese rice wine (huangjiu) contains a wide range of bioactive peptides that are produced during the multi-species fermentation process. To clarify the regulation effects of lipid metabolism and gut microbiota by huangjiu bioactive peptides, three huangjiu peptides were isolated, purified and characterized by hyper-filtration, macroporous resin, gel filtration separation and structural identification. Meanwhile, a mouse model of high-fat diet-induced hyperlipidemia was established to study the effects of huangjiu peptides on serum biomarker, hepatic metabolism and gut microbiota dysbiosis. Experimental results showed that huangjiu peptides T1 and T2 (HpT1, HpT2) treatment alleviated the increase in serum total cholesterol, triglyceride, low-density lipoprotein cholesterol levels and aberrant hepatic lipid accumulation in the high-fat diet-induced hyperlipidemia mice. Furthermore, HpT2 and HpT1 restored the α-diversity and structure of gut microbial community after hyperlipidemia-induced microbiota disturbance compared with simvastatin and HpT3. The administration of HpT2 and HpT1 regulated the microbiota-mediated gut ecology through alterations of characteristic taxa including Lactobacillus, Ileibacterium, Faecalibaculum and Alloprevotella by linear discriminant analysis effect size analysis. Collectively, our results offer new insights into the abilities of food-derived peptides on alleviation of high-fat diet-induced hyperlipidemia, hepatic steatosis and gut dysbiosis in mice.

13.
BMC Pregnancy Childbirth ; 21(1): 435, 2021 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-34158009

RESUMO

BACKGROUND: Asthma is the most common respiratory disease among children, while atopic diseases such as atopic dermatitis affect about 20% of infants under 2 years of age. Studies suggested that these conditions might be related to prenatal depression or anxiety. This study aimed to explore the association between prenatal mental disorders and childhood asthma or atopic disease in a systematic review and meta-analysis. METHODS: PubMed, Embase, and the Cochrane Library were searched up to May 2020. The primary outcome was childhood asthma and childhood atopic dermatitis. Random-effects models were used because of high heterogeneity indicated by I2 > 50% and Q-test P < 0.10. RESULTS: A total of 598 studies were initially identified, but nine studies met the inclusion criteria. Prenatal mental disorder was associated with childhood asthma (n = 6 studies; ES = 1.146, 95%CI: 1.054-1.245, P = 0.001; I2 = 93.5%, Pheterogeneity < 0.001) whereas no significant association was found for childhood atopic dermatitis (n = 4 studies; ES = 1.211, 95%CI: 0.982-1.494, P = 0.073; I2 = 78.5%, Pheterogeneity < 0.001). Childhood asthma seems to be related more to depression (n = 1 study; ES = 1.170, 95%CI: 1.061-1.291, P = 0.002) and anxiety/depression (n = 4 studies; ES = 1.157, 95%CI: 1.050-1.275, P = 0.073; I2 = 95.3%, Pheterogeneity < 0.001). CONCLUSION: This meta-analysis demonstrated that prenatal mental disorders increase the risk of childhood asthma. We limited the included samples to pregnant women to investigate the association between prenatal psychological factors and offspring's physical health. Future studies should include large high-quality cohort studies to investigate the behavioral, environmental, and genetic causes for this association.


Assuntos
Ansiedade/psicologia , Asma/epidemiologia , Depressão/psicologia , Dermatite Atópica/epidemiologia , Complicações na Gravidez/psicologia , Saúde da Criança , Feminino , Humanos , Gravidez
14.
Eur J Nucl Med Mol Imaging ; 48(8): 2384-2394, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33866409

RESUMO

PURPOSE: The aim of the study was to determine a faster PET acquisition protocol for a total-body PET/CT scanner by assessing the image quality that is equivalent to a conventional digital PET/CT scanner from both a phantom and a clinical perspective. METHODS: A phantom study using a NEMA/IEC NU-2 body phantom was first performed in both a total-body PET/CT (uEXPLORER) and a routine digital PET/CT (uMI 780), with a hot sphere to background activity concentration ratio of 4:1. The contrast recovery coefficient (CRC), background variability (BV), and recovery coefficient (RC: RCmax and RCmean) were assessed in the uEXPLORER with different scanning durations and reconstruction protocols, which were compared to those acquired from the uMI 780 with clinical acquisition settings. The coefficient of variation (COV) of the uMI 780 with clinical settings was calculated and used as a threshold reference to determine the optimized scanning duration and reconstruction protocol for the uEXPLORER. The obtained protocol from the phantom study was subsequently tested and validated in 30 oncology patients. Images acquired from the uMI 780 with 2-3 min per bed position were referred as G780 and served as the reference for comparison. All PET raw data from the uEXPLORER were reconstructed using the data-cutting technique to simulate a 30-s, 45-s, or 60-s acquisition duration, respectively. The iterations were 2 and 3 for the uEXPLORER, referred as G30s_3i, G45s_2i, G45s_3i, G60s_2i, and G60s_3i, respectively. A 5-point Likert scale was used in the qualitative analysis to assess the image quality. The image quality was also evaluated by the liver COV, the lesion target-to-background ratio (TBR), and the lesion signal-to-noise ratio (SNR). RESULTS: In the phantom study, CRC, BV, RCmax, and RCmean in the uEXPLORER with different scanning durations and reconstruction iterations were compared with those in the uMI 780 with clinical settings. A minor fluctuation was found among different scanning durations. COV of the uMI 780 with clinical settings was 11.6%, and a protocol with a 30-45-s scanning duration and 2 or 3 iterations for the uEXPLORER was found to provide an equivalent image quality as the uMI 780. An almost perfect agreement was shown with a kappa value of 0.875. The qualitative score of the G30s_3i in the uEXPLORER was inferior to the G780 reference (p = 0.001); however, the scores of other groups in the uEXPLORER with a 45-s and above acquisition time were higher than the G780 in the uMI 780. In quantitative analysis, the delay time between the two scans in the two orders was not significantly different. There was no significant difference of the liver COV between the G780 and G30s_3i (p = 0.162). A total of 33 lesions were analyzed in the clinical patient study. There was no significant difference in lesion TBR between the reference G780 and the G45s_2i obtained from the uEXPLORER (p = 0.072), while the latter showed a higher lesion SNR value compared to that in uMI 780 with clinical settings (p < 0.001). CONCLUSIONS: This study showed that a fast PET protocol with a 30-45-s acquisition time in the total-body uEXPLORER PET/CT can provide an equivalent image quality as the conventional digital uMI 780 PET/CT with longer clinical acquisition settings.


Assuntos
Neoplasias , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Humanos , Processamento de Imagem Assistida por Computador , Neoplasias/diagnóstico por imagem , Imagens de Fantasmas , Tomografia Computadorizada por Raios X
15.
Allergy Asthma Proc ; 42(2): e47-e54, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33685566

RESUMO

Introduction: Atopic dermatitis (AD) is a chronic and relapsing inflammatory skin disease characterized by severe pruritus and eczematous skin lesions. Subcutaneous immunotherapy (SCIT) refers to repeated contact with gradually increasing doses of allergen extracts, which improve patient tolerance to such allergens and controls, or reduces allergic symptoms. This study aimed to explore the long-term efficacy and safety of SCIT for patients with AD sensitized to house-dust mite (HDM). Methods: We conducted a retrospective analysis of 378 patients with HDM-sensitized AD. Among these patients, 164 received SCIT plus pharmacotherapy for 3 years (SCIT group) and the other 214 patients received only pharmacotherapy (non-SCIT group). The scoring atopic dermatitis (SCORAD) and pruritus visual analog scale (VAS) scores, laboratory test results, and adverse effects were recorded. Results: The SCORAD and pruritus VAS scores significantly decreased in the SCIT group. Also, the SCIT group showed higher reduction ratios of SCORAD and pruritus VAS scores than those observed in the non-SCIT group at 3 years after treatment initiation. The risk of development of new sensitization was higher in the non-SCIT group than in the SCIT group (relative risk 1.92 [95% confidence interval {CI}, 1.30-2.85]; p < 0.05). The eosinophil count of the participants significantly differed in the complete response (CR) group (p < 0.05) but not in the non-CR group (p = 0.098). However, the serum total immunoglobulin E value was not significantly reduced (p = 0.204). Of 8421 injections given to the patients, 231 injections (2.74%) showed adverse effects during the treatment period. Conclusion: Three years of SCIT can significantly reduce the severity and pruritus of moderate-to-severe AD with HDM sensitization. Patients who are multisensitized can also benefit from HDM SCIT. Patients can achieve long-term effects, such as prevention of neoallergen sensitization and inhibition of the allergy march.


Assuntos
Alérgenos/administração & dosagem , Antígenos de Dermatophagoides/administração & dosagem , Dermatite Atópica/terapia , Dermatophagoides farinae/imunologia , Dermatophagoides pteronyssinus/imunologia , Dessensibilização Imunológica , Prurido/terapia , Adolescente , Adulto , Alérgenos/efeitos adversos , Alérgenos/imunologia , Animais , Antígenos de Dermatophagoides/efeitos adversos , Antígenos de Dermatophagoides/imunologia , Criança , Pré-Escolar , Dermatite Atópica/diagnóstico , Dermatite Atópica/imunologia , Dessensibilização Imunológica/efeitos adversos , Feminino , Humanos , Tolerância Imunológica , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Prurido/diagnóstico , Prurido/imunologia , Estudos Retrospectivos , Índice de Gravidade de Doença , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
16.
J Cancer ; 12(5): 1555-1562, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33532001

RESUMO

Purpose: There is limited standard treatment for patients with advanced cholangiocarcinoma after refractory of chemotherapy. Apatinib is a tyrosine kinase inhibitor targeting VEGFR-2, which exhibited broad-spectrum antitumor activities in previous studies. We aim to evaluate the efficacy and safety of apatinib as non-first-line treatment in patients with advanced cholangiocarcinoma. Methods: This was a prospective open-label phase II trial (NCT03251443). Patients with pathology-confirmed cholangiocarcinoma after prior systemic therapy were enrolled. Participants were treated with apatinib 500 mg orally once daily. The primary end point was overall response rate (ORR). Results: Between August 8, 2017 and November 13, 2018, 30 patients participated in this study, and 26 patients received apatinib treatment except 4 patients withdrew consent before the first dosage. For full analysis set, the ORR was 11.5% and the disease control rate was 50.0%. 3 patients (11.5%) achieved partial response and no patients achieved complete response. The median progression free time was 2.0 (95% CI: 0.7-3.3) months and median overall survival was 9. 0 (95% CI: 4.6-13.4) months. The most common adverse events of any grade were fatigue (80.8%), hypertension (73.1%) and decreased appetite (38.5%). Grade 3 adverse events occurred in 23.1% patients and no grade 4 adverse events occurred. The most common grade 3 adverse events were hypertension (23.1%) and elevated transaminase (11.5%). Conclusion: Apatinib as non-first-line monotherapy has potential therapeutic efficacy in patients with advanced cholangiocarcinoma.

17.
Org Lett ; 23(5): 1594-1599, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33596086

RESUMO

A novel method to synthesize 2-azaaryl tetrahydroquinolines by the base-promoted tandem reaction of azaaryl methyl amines and styrene derivatives is reported (over 30 examples, yields up to 95%). Mechanistic probe experiments demonstrate that the deprotonation of the benzylic C-H bond and the addition to the styrene vinyl group proceeds via the SNAr mechanism.

18.
Eur J Nucl Med Mol Imaging ; 48(6): 1726-1735, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33388972

RESUMO

PURPOSE: In this paper, we aimed to evaluate the positron emission tomography (PET) performance of, to the best of our knowledge, the third commercially available whole-body integrated PET/magnetic resonance (MR) system. METHODS: The PET system performance was measured following the NEMA standards with and without simultaneous MR operation. PET spatial resolution, sensitivity, scatter fraction, count-rate performance, accuracy of count losses and random corrections, image quality, and time-of-flight (TOF) resolution were quantitatively evaluated. Clinical scans were acquired at the PET/MR system and compared with images acquired at a PET/CT with the same digital detector technology. RESULTS: Measurement results of essential PET performance were reported in the form of MR idle (MR pulsing). The axial, radial, and tangential spatial resolutions were measured as 2.72 mm (2.73 mm), 2.86 mm (2.85 mm), and 2.81 mm (2.82 mm) FWHM, respectively, at 1 cm radial offset. The NECR peak was measured as 129.2 kcps (129.5 kcps) at 14.7 kBq mL-1 (14.2 kBq mL-1). The scatter fraction at NECR peak was 37.9% (36.5%), and the maximum slice error below NECR was 4.1% (4.5%). Contrast recovery coefficients ranged from 51.8% (52.3%) for 10 mm hot sphere to 87.3% (87.2%) for 37 mm cold sphere. TOF resolution at 5.3 kBq mL-1 was measured at 535 ps (540 ps). With point source, TOF was measured to be 474 ps (485 ps). Clinical scans revealed similar image quality from the PET/MR and the comparative PET/CT system. CONCLUSION: The PET performance of the newly introduced integrated PET/MR system is not significantly affected by the simultaneous operation of an MR sequence (2-point DIXON sequence). Measurement results demonstrate comparable performance with other state-of-the-art PET/MR systems. The clinical benefits of high spatial resolution and long axial coverage remain to be further evaluated in specific clinical imaging applications.


Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Humanos , Espectroscopia de Ressonância Magnética , Imagens de Fantasmas , Padrões de Referência
19.
Eur J Nucl Med Mol Imaging ; 48(6): 1966-1975, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33244618

RESUMO

PURPOSE: The purpose was to explore the effects of total-body PET/CT with half-dose 18F-FDG activity on image quality, compared with those of conventional PET/CT with clinical routine full-dose 18F-FDG in lung cancer. METHODS: Fifty-six primary lung cancer patients who underwent total-body PET/CT on a uEXPLORER scanner with half-dose (1.85 MBq/kg) 18F-FDG activity before treatment were retrospectively studied; among them, 28 patients were confirmed by postoperative pathologic examination and 28 patients by biopsy. After matching with the pathological study results, the other 28 patients with lung cancer who underwent surgery were selected for the full-dose (3.70 MBq/kg) group. Patients in the full-dose group were studied with a conventional uM780 PET/CT scanner. The acquisition time of the half-dose group was 15 min, split into 4-min and 2-min duration groups, which were all referred to as G15, G4 and G2, respectively. The PET/CT scanning speed in the full-dose group was 2 min/bed. Image quality was evaluated by subjective and objective analyses. The subjective analysis method was carried out with a 5-point scale (5-excellent, 1-poor). Objective analysis indicators of PET image quality included the SUVmax, SUVmean and signal-to-noise ratio (SNR) of the liver; the SUVmax and SUVmean of the blood pool; and the SUVmax and tumour-to-background ratio (TBR) of the lesions. G15 served as the reference for G2 and G4 to test lesion detectability. RESULTS: Image quality scores in G2 (4.3 ± 0.7) were significantly higher than those in the full-dose group (3.7 ± 0.6) (p = 0.004). The mean and SD of the image quality scores in G4 and G15 were 4.9 ± 0.2 and 5.0 ± 0.0, respectively. The liver SNR in G2 was significantly higher than that in the full-dose group; the corresponding SNR were 11.7 ± 1.5 and 8.3 ± 1.2 (p < 0.001), respectively. The liver SNR significantly increased with the time of acquisition among G2, G4 and G15 (11.1 ± 1.7, 15.2 ± 3.4 and 30.5 ± 6.0, all p < 0.05). G15 served as the reference, and all these lesions (100%) could be identified by G2 and G4. CONCLUSION: Total-body PET/CT with half-dose 18F-FDG activity in G2 and G4 achieved comparable image quality to conventional PET/CT, and its image quality was better than that of conventional PET/CT with clinical routine full-dose 18F-FDG in lung cancer.


Assuntos
Fluordesoxiglucose F18 , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
20.
PET Clin ; 16(1): 9-14, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33218606

RESUMO

"The initial experience of using total-body PET/computed tomography (CT) (uExplorer) in Zhongshan Hospital, Fudan University, is described. Compared with conventional PET/CT, total-body PET/CT imaging provides more comprehensive information for evaluation of disease. Using fludeoxyglucose F 18, regular-dose (3.7 MBq/kg), low-dose (1.85 MBq/kg), or extra low-dose (0.37 MBq/kg) scanning, as well as high-quality imaging, protocols were used in clinical practice according to the situation. Dynamic studies were also used to assess tumor biological characteristics or for radiotracer angiography."


Assuntos
Neoplasias/diagnóstico por imagem , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Imagem Corporal Total/métodos , China , Humanos , Universidades
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