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1.
BMC Cancer ; 24(1): 816, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38977966

RESUMO

Anaplastic thyroid carcinoma (ATC) is a rare but highly aggressive thyroid cancer with poor prognosis. Killing cancer cells by inducing DNA damage or blockage of DNA repair is a promising strategy for chemotherapy. It is reported that aldehyde-reactive alkoxyamines can capture the AP sites, one of the most common DNA lesions, and inhibit apurinic/apyrimidinic endonuclease 1(APE1)-mediated base excision repair (BER), leading to cell death. Whether this strategy can be employed for ATC treatment is rarely investigated. The aim of this study is to exploit GSH-responsive AP site capture reagent (AP probe-net), which responses to the elevated glutathione (GSH) levels in the tumor micro-environment (TME), releasing reactive alkoxyamine to trap AP sites and block the APE1-mediated BER for targeted anti-tumor activity against ATC. In vitro experiments, including MTT andγ-H2AX assays, demonstrate their selective cytotoxicity towards ATC cells over normal thyroid cells. Flow cytometry analysis suggests that AP probe-net arrests the cell cycle in the G2/M phase and induces apoptosis. Western blotting (WB) results show that the expression of apoptotic protein increased with the increased concentration of AP probe-net. Further in vivo experiments reveal that the AP probe-net has a good therapeutic effect on subcutaneous tumors of the ATC cells. In conclusion, taking advantage of the elevated GSH in TME, our study affords a new strategy for targeted chemotherapy of ATC with high selectivity and reduced adverse effects.


Assuntos
Apoptose , Glutationa , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Carcinoma Anaplásico da Tireoide/patologia , Carcinoma Anaplásico da Tireoide/metabolismo , Humanos , Glutationa/metabolismo , Animais , Camundongos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/metabolismo , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Reparo do DNA/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , Dano ao DNA/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacos
2.
Environ Health ; 23(1): 45, 2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38702703

RESUMO

BACKGROUND: Volatile organic compounds (VOCs) encompass hundreds of high production volume chemicals and have been reported to be associated with adverse respiratory outcomes such as chronic obstructive pulmonary disease (COPD). However, research on the combined toxic effects of exposure to various VOCs on COPD is lacking. We aimed to assess the effect of VOC metabolite mixture on COPD risk in a large population sample. METHODS: We assessed the effect of VOC metabolite mixture on COPD risk in 5997 adults from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2020 (pre-pandemic) using multivariate logistic regression, Bayesian weighted quantile sum regression (BWQS), quantile-based g-Computation method (Qgcomp), and Bayesian kernel machine regression (BKMR). We explored whether these associations were mediated by white blood cell (WBC) count and total bilirubin. RESULTS: In the logistic regression model, we observed a significantly increased risk of COPD associated with 9 VOC metabolites. Conversely, N-acetyl-S-(benzyl)-L-cysteine (BMA) and N-acetyl-S-(n-propyl)-L-cysteine (BPMA) showed insignificant negative correlations with COPD risk. The overall mixture exposure demonstrated a significant positive relationship with COPD in both the BWQS model (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.06, 1.58) and BKMR model, and with marginal significance in the Qgcomp model (adjusted OR = 1.22, 95% CI: 0.98, 1.52). All three models indicated a significant effect of the VOC metabolite mixture on COPD in non-current smokers. WBC count mediated 7.1% of the VOC mixture associated-COPD in non-current smokers. CONCLUSIONS: Our findings provide novel evidence suggesting that VOCs may have adverse associations with COPD in the general population, with N, N- Dimethylformamide and 1,3-Butadiene contributing most. These findings underscore the significance of understanding the potential health risks associated with VOC mixture and emphasize the need for targeted interventions to mitigate the adverse effects on COPD risk.


Assuntos
Inquéritos Nutricionais , Doença Pulmonar Obstrutiva Crônica , Compostos Orgânicos Voláteis , Humanos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Compostos Orgânicos Voláteis/urina , Masculino , Pessoa de Meia-Idade , Feminino , Estados Unidos/epidemiologia , Adulto , Idoso , Análise de Mediação , Poluentes Atmosféricos/análise , Modelos Logísticos
3.
Angew Chem Int Ed Engl ; 63(3): e202316488, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38009610

RESUMO

Inorganic materials depleted of heavy stable isotopes are known to deviate strongly in some physicochemical properties from their isotopically natural counterparts. Here we explored for the first time the effect of simultaneous depletion of the heavy carbon, hydrogen, oxygen and nitrogen isotopes on the bacterium E. coli and the enzymes expressed in it. Bacteria showed faster growth, with most proteins exhibiting higher thermal stability, while for recombinant enzymes expressed in depleted media, faster kinetics was discovered. At room temperature, luciferase, thioredoxin and dihydrofolate reductase and Pfu DNA polymerase showed up to a 250 % increase in activity compared to the native counterparts, with an additional ∼50 % increase at 10 °C. Diminished conformational and vibrational entropy is hypothesized to be the cause of the accelerated kinetics. Ultralight enzymes may find an application where extreme reaction rates are required.


Assuntos
Escherichia coli , Hidrogênio , Escherichia coli/metabolismo , Hidrogênio/metabolismo , Bactérias , Tetra-Hidrofolato Desidrogenase/genética , Cinética
4.
BMC Med Imaging ; 23(1): 84, 2023 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-37328753

RESUMO

BACKGROUND: This study aimed to develop and validate an AI (artificial intelligence)-aid method in myocardial perfusion imaging (MPI) to differentiate ischemia in coronary artery disease. METHODS: We retrospectively selected 599 patients who had received gated-MPI protocol. Images were acquired using hybrid SPECT-CT systems. A training set was used to train and develop the neural network and a validation set was used to test the predictive ability of the neural network. We used a learning technique named "YOLO" to carry out the training process. We compared the predictive accuracy of AI with that of physician interpreters (beginner, inexperienced, and experienced interpreters). RESULTS: Training performance showed that the accuracy ranged from 66.20% to 94.64%, the recall rate ranged from 76.96% to 98.76%, and the average precision ranged from 80.17% to 98.15%. In the ROC analysis of the validation set, the sensitivity range was 88.9 ~ 93.8%, the specificity range was 93.0 ~ 97.6%, and the AUC range was 94.1 ~ 96.1%. In the comparison between AI and different interpreters, AI outperformed the other interpreters (most P-value < 0.05). CONCLUSION: The AI system of our study showed excellent predictive accuracy in the diagnosis of MPI protocols, and therefore might be potentially helpful to aid radiologists in clinical practice and develop more sophisticated models.


Assuntos
Doença da Artéria Coronariana , Imagem de Perfusão do Miocárdio , Humanos , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Estudos Retrospectivos , Imagem de Perfusão do Miocárdio/métodos , Inteligência Artificial , Doença da Artéria Coronariana/diagnóstico por imagem , Angiografia Coronária/métodos
5.
Alzheimers Dement ; 19(4): 1491-1502, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35924765

RESUMO

Isoaspartate (isoAsp) is a damaging amino acid residue formed in proteins as a result of spontaneous deamidation. IsoAsp disrupts protein structures, making them prone to aggregation. Here we strengthened the link between isoAsp and Alzheimer's disease (AD) by novel approaches to isoAsp analysis in human serum albumin (HSA), the most abundant blood protein and a major carrier of amyloid beta (Aß) and phosphorylated tau (p-tau) in blood. We discovered a reduced amount of anti-isoAsp antibodies (P < 0.0001), an elevated isoAsp level in HSA (P < 0.001), more HSA aggregates (P < 0.0001), and increased levels of free Aß (P < 0.01) in AD blood compared to controls. We also found that deamidation significantly reduces HSA capacity to bind with Aß and p-tau (P < 0.05). These suggest the presence in AD of a bottleneck in clearance of Aß and p-tau, leading to their increased concentrations in the brain and facilitating their aggregations there.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/metabolismo , Ácido Isoaspártico/química , Ácido Isoaspártico/metabolismo , Peptídeos beta-Amiloides/metabolismo , Proteínas tau/metabolismo , Proteínas Sanguíneas/metabolismo , Encéfalo/metabolismo
6.
Molecules ; 28(20)2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37894596

RESUMO

Peptides released on frogs' skin in a stress situation represent their only weapon against micro-organisms and predators. Every species and even population of frog possesses its own peptidome being appropriate for their habitat. Skin peptides are considered potential pharmaceuticals, while the whole peptidome may be treated as a taxonomic characteristic of each particular population. Continuing the studies on frog peptides, here we report the peptidome composition of the Central Slovenian agile frog Rana dalmatina population. The detection and top-down de novo sequencing of the corresponding peptides was conducted exclusively by tandem mass spectrometry without using any chemical derivatization procedures. Collision-induced dissociation (CID), higher energy collision-induced dissociation (HCD), electron transfer dissociation (ETD) and combined MS3 method EThcD with stepwise increase of HCD energy were used for that purpose. MS/MS revealed the whole sequence of the detected peptides including differentiation between isomeric Leu/Ile, and the sequence portion hidden in the disulfide cycle. The array of the discovered peptide families (brevinins 1 and 2, melittin-related peptides (MRPs), temporins and bradykinin-related peptides (BRPs)) is quite similar to that of R. temporaria. Since the genome of this frog remains unknown, the obtained results were compared with the recently published transcriptome of R. dalmatina.


Assuntos
Ranidae , Espectrometria de Massas em Tandem , Humanos , Animais , Espectrometria de Massas em Tandem/métodos , Sequência de Aminoácidos , Anuros , Análise de Sequência de Proteína/métodos , Pele/química
7.
Hell J Nucl Med ; 26(1): 35-40, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37031421

RESUMO

OBJECTIVE: To observe the disease development and outcome of Graves' disease (GD) patients within 1 year after iodine-131 (131I) treatment, and analyze the factors affecting the treatment effect. SUBJECTS AND METHODS: Clinical data of 221 patients who received the first treatment with 131I in our department from June 2016 to October 2018 were retrospectively analyzed and they were followed up at 3 months, 6 months and 1 year after the treatment. According to the three follow-up records, the cure rate was calculated and the follow-up chart was drawn. The factors that may affect the clinical cure were analyzed according to the follow-up results after 1 year: Independent risk factors affecting the prognosis were screened out by Logistic regression analysis, and the effects of the above factors on the prognosis were further analyzed by Chi-square test, and the cure multiple relationship caused by the influencing factors was analyzed by Logistic regression analysis. RESULTS: The cure rate was 58.82% and the effective rate was 71.95%. At the 3-month follow-up, 11 patients (4.98%) presented complete response, 99 patients (44.80%) presented hypothyroidism, 93 patients (42.08%) presented partial response, and 18 patients (8.14%) presented no effect or recurrence. At 6 months, 18 cases (8.14%) had complete response, 90 cases (40.72%) had hypothyroidism, 59 cases (26.70%) had partial response, and 54 cases (24.43%) had no effect or recurrence. At 12 months, 36 cases (16.29%) had complete response, 94 cases (42.53%) had hypothyroidism, 29 cases (13.12%) had partial response, and 62 cases (28.05%) had no effect or recurrence. Thyroid weight and thyroid peroxidase antibody (TPOAb) were the influencing factors. Among all patients, patients with thyroid weight ≤28.70g were 4.25 times more likely to achieve clinical cure than patients with >28.70g [OR (95%CI):4.252 (2.383-7.588), P<0.01)], female patients with the thyroid weight ≤28.70g was 5.78 times than those with >28.70g [OR (95%CI): 5.776 (2.951-11.308), P<0.01]. In male, patients with TPOAb≤449.00IU/mL were 0.27 times more likely to achieve clinical cure than those with >449.00IU/mL [OR (95%CI): 0.274 (0.081-0.919), P<0.05]. CONCLUSION: Iodine-131 was an effective treatment to GD. Thyroid weight before treatment was the influencing factor for all patients and female patients, while TPOAb was the influencing factor for male patients.


Assuntos
Doença de Graves , Hipertireoidismo , Hipotireoidismo , Humanos , Masculino , Feminino , Estudos Retrospectivos , Hipertireoidismo/radioterapia , Hipertireoidismo/complicações , Radioisótopos do Iodo/uso terapêutico , Doença de Graves/radioterapia , Resultado do Tratamento
8.
Anal Chem ; 94(45): 15772-15780, 2022 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-36377428

RESUMO

Most drugs are used in the clinic and drug candidate target multiple proteins, and thus detailed characterization of their efficacy targets is required. While current methods rely on quantitative measurements at thermodynamic equilibrium, kinetic parameters such as the residence time of a drug on its target provide a better proxy for efficacy in vivo. Here, we present a residence time proteome integral solubility alteration (ResT-PISA) assay, which facilitates monitoring temporal protein solubility profiles after drug removal ("off-curve") in cell lysates or intact cells, quantifying the lifetime of drug-target interaction. A compressed version of the assay measures the integral under the off-curve enabling the multiplexing of binding affinity and residence time assessments into a single proteomic analysis. We introduce a combined scoring system for three parametric dimensions to improve prioritization of targets. By providing complementary information to other characteristics of drug-target interaction, the ResT-PISA approach will be useful in drug development and precision medicine.


Assuntos
Proteoma , Proteômica , Proteoma/química , Proteômica/métodos , Solubilidade , Termodinâmica , Cinética
9.
IUBMB Life ; 74(5): 433-445, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35112451

RESUMO

Bovine serum albumin (BSA) has been employed as a mild biological template in nanoscale particles. Copper sulfide (CuS) has been used for photothermal therapy (PTT) in several studies. In this study, we aimed to synthesize the 131 I-labeled BSA-modified CuS nanoparticles (131 I-BSA@CuS), with attributes of both radiotherapy and PTT, as a therapeutic agent against anaplastic thyroid carcinoma (ATC). BSA@CuS nanoparticles were prepared using the solvothermal reaction and then labeled with Na131 I by the chloramine-T method. The products were characterized and their cytotoxicity was investigated in vitro and in vivo. The therapeutic efficacy of 131 I-BSA@CuS was evaluated in ARO cell (an ATC cell line) subcutaneous tumors. The nanoparticles showed good biocompatibility and low toxicity in vitro and in vivo. BSA@CuS rapidly and effectively converted the light energy from an 808 nm laser into thermal energy with a conversion efficiency of 28.07%. SPECT/CT imaging demonstrated that the accumulation of radioactivity peaked within 24 hr and resided in the tumors for 5 days post intratumoral injection. In vivo assays indicated that, compared to monotherapy, the synthesized nanoparticles employing both PTT and radiotherapy possess better therapeutic efficacy against tumors. The synthesized nanomaterial showed uniform dispersion, good stability and aqueous solubility, excellent photothermal properties, and long-term retention in ATC. Hence, combined radiotherapy and PTT can significantly inhibit tumor growth compared to monotherapy, and can be applied in clinical settings.


Assuntos
Nanopartículas , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Cobre , Humanos , Fototerapia/métodos , Terapia Fototérmica , Soroalbumina Bovina , Carcinoma Anaplásico da Tireoide/radioterapia , Neoplasias da Glândula Tireoide/radioterapia
10.
J Nanobiotechnology ; 20(1): 247, 2022 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-35642064

RESUMO

Exosomes are nanoscale monolayer membrane vesicles that are actively endogenously secreted by mammalian cells. Currently, multifunctional exosomes with tumor-targeted imaging and therapeutic potential have aroused widespread interest in cancer research. Herein, we developed a multifunctional HEK-293T exosome-based targeted delivery platform by engineering HEK-293T cells to express a well-characterized exosomal membrane protein (Lamp2b) fused to the αv integrin-specific iRGD peptide and tyrosine fragments. This platform was loaded with doxorubicin (Dox) and labeled with radioiodine-131 (131I) using the chloramine-T method. iRGD exosomes showed highly efficient targeting and Dox delivery to integrin αvß3-positive anaplastic thyroid carcinoma (ATC) cells as demonstrated by confocal imaging and flow cytometry in vitro and an excellent tumor-targeting capacity confirmed by single-photon emission computed tomography-computed tomography after labeling with 131I in vivo. In addition, intravenous injection of this vehicle delivered Dox and 131I specifically to tumor tissues, leading to significant tumor growth inhibition in an 8505C xenograft mouse model, while showing biosafety and no side effects. These as-developed multifunctional exosomes (denoted as Dox@iRGD-Exos-131I) provide novel insight into the current treatment of ATC and hold great potential for improving therapeutic efficacy against a wide range of integrin αvß3-overexpressing tumors.


Assuntos
Exossomos , Neoplasias , Animais , Doxorrubicina , Exossomos/metabolismo , Células HEK293 , Humanos , Integrina alfaVbeta3/metabolismo , Radioisótopos do Iodo/análise , Radioisótopos do Iodo/metabolismo , Camundongos , Neoplasias/tratamento farmacológico , Neoplasias/radioterapia
11.
Hell J Nucl Med ; 25(2): 119-124, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35913857

RESUMO

OBJECTIVE: To analyse predictive factors to ensure the efficacy of iodine-131 (131I) therapy on Graves' disease (GD). SUBJECTS AND METHODS: Graves' disease patients from three tertiary medical centers were enrolled. Serological data, thyroid mass estimation, thyroid radioactive iodine uptake, thyroid texture and thyroid murmurs (bruits) were recorded. Iodine-131 treatment was performed by applying a formulated calculation method. After one year of follow-up, GD patients with euthyroidism and hypothyroidism were classified as the cured group, and the other thyroid function status refers to the uncured group. These analyses were performed by using SPSS17.0 software. A P value of less than 0.05 was considered statistically significant. RESULTS: A total of 970 GD patients, of which 540 patients (55.7%) belonged to the cured group, and 430 patients (44.3%) belonged to the uncured group, participated in the current analyses. Multivariate logistic regression analysis was performed. Moreover, estimated thyroid mass, thyroid murmurs (bruits), prescribed 131I dosage, FT3 and FT4 have independent prognostic value for 131I efficacy, and their odds ratios are 1.368, 2.283, 1.326, 1.467 and 1.419, respectively. CONCLUSION: Graves' disease patients who are undergoing 131I therapy using the formulated dosage calculation could be influenced by thyroid mass, thyroid murmurs, 131I dosage and thyroid function.


Assuntos
Doença de Graves , Neoplasias da Glândula Tireoide , Humanos , Radioisótopos do Iodo , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
12.
Wei Sheng Yan Jiu ; 51(1): 45-50, 2022 Jan.
Artigo em Zh | MEDLINE | ID: mdl-35341493

RESUMO

OBJECTIVE: Evaluate the health risks of metalloid and heavy metals in rural drinking water in Shaanxi Province, and provide a scientific basis for ensuring the safety of drinking water for rural residents. METHODS: In 2020, the rural drinking water in Shaanxi Province were monitored, referring to the "Sanitary Standards for Drinking Water"(GB 5749-2006) for arsenic(As), cadmium(Cd), chromium(Cr~(6+)), lead(Pb), and mercury(Hg) in the water. To evaluate the concentration of five metalloid and heavy metals, the health risk assessment method recommended by United States Environmental Protection Agency was used to evaluate the health risks of adults in rural areas exposed to metalloid and heavy metals through drinking water. RESULTS: In 2020, a total of 6232 water samples were monitored. The concentrations of Cd, Pb and Hg in the water all met the standards, and the compliance rates of As and Cr~(6+) were 99.98% and 98.09%, respectively. The carcinogenic risk level of As was 3.53×10~(-5), and the non-carcinogenic health risk levels of the four heavy metals in descending order were Pb>Cr~(6+)>Cd>Hg, and the total risk level was 0.105. The concentration level of As and the distribution of health risk levels were all in northern Shaanxi>Guanzhong region>southern Shaanxi(P<0.05). The concentration level and health risk level distribution of As and Cr~(6+) were all groundwater>surface water(P<0.05), and the concentration level and health risk level distribution of Cd, Pb and Hg were all surface water>groundwater(P<0.05). CONCLUSION: There was a potential health risk of As exposure in rural drinking water in Shaanxi Province in 2020. The non-carcinogenic health risks of four heavy metals intake of Cd, Hg, Pb and Cr~(6+) through drinking water were still at an acceptable level. The control of arsenic pollution in drinking water should be further strengthened to ensure drinking water safety.


Assuntos
Água Potável , Metaloides , Metais Pesados , Poluentes Químicos da Água , Adulto , Água Potável/análise , Monitoramento Ambiental , Humanos , Metais Pesados/análise , Medição de Risco , Estados Unidos , Poluentes Químicos da Água/análise
13.
Med Sci Monit ; 27: e929590, 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33568620

RESUMO

BACKGROUND The aim of this study was to investigate the effects of ¹³¹I therapy on complete blood count (CBC) in patients with differentiated thyroid cancer (DTC). MATERIAL AND METHODS We analyzed CBC in 542 patients with DTC who were grouped according to treatment cycles and cumulative dose and then subdivided by sex and age. The effects of ¹³¹I therapy among the different groups and subgroups were analyzed. RESULTS After sorting patients by treatment cycles and doses, ¹³¹I therapy was found to have different effects on CBC depending on patient sex and age. The effect on white blood cell (WBC) counts persisted longer in women, while increases in hemoglobin (Hb) were more significant in men. The influence on red blood cell (RBC) counts was short-lived in patients aged 45 to 54 years. Monocyte counts were significantly decreased only in patients aged 55 years and older who had undergone 3 or 4 treatment cycles. In men, CBC was more affected by cumulative dose. ¹³¹I therapy only influenced platelet and monocyte counts in patients aged 55 years or older. Hb was significantly decreased and increased in the high- and low-dose groups, respectively. No significant complications were observed during follow-up. CONCLUSIONS ¹³¹I therapy had a greater impact on WBC counts in women, while changes in RBC counts and Hb were more obvious in men. During ¹³¹I therapy, clinicians should pay attention to different CBC indicators based on a patient's sex and age, but risks associated with an altered CBC are unlikely to outweigh the benefits of 131I. The results of the present study may help alleviate the concerns of a large proportion of patients with DTC and their families about the effects of ¹³¹I therapy on CBC.


Assuntos
Medula Óssea/efeitos da radiação , Radioisótopos do Iodo/efeitos adversos , Compostos Radiofarmacêuticos/efeitos adversos , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/radioterapia , Adolescente , Adulto , Fatores Etários , Idoso , Relação Dose-Resposta à Radiação , Contagem de Eritrócitos , Feminino , Seguimentos , Hemoglobinas/análise , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Valores de Referência , Fatores de Risco , Fatores Sexuais , Fatores de Tempo , Adulto Jovem
14.
Med Sci Monit ; 27: e928796, 2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33497370

RESUMO

BACKGROUND Although radioiodine therapy (RIT) efficacy is thoroughly validated for Graves disease (GD), there is a lack of research on the predictive factors of RIT, especially the optimal thyroid-absorbed dose (TD) with a shorter effective half-life (Teff ≤5 days). The goal of this study was to explore the predictive value of TD in GD patients receiving RIT with a shorter Teff. MATERIAL AND METHODS We studied 208 GD patients receiving RIT with a shorter Teff. Plotting the receiver-operating characteristic (ROC) curve verified the accuracy of TD for predicting RIT efficacy in GD patients. In addition, we conducted univariate and multivariate analyses to investigate the influence of 14 factors, including thyroid weight, TD, 24-h radioiodine uptake rate (RAIU), the highest RAIU, thyrotrophin receptor antibody level, thyroglobulin antibody level, thyroid peroxidase antibody level, and others, on curative effects of RIT. RESULTS Of the 208 study participants, complete remission and the total effectiveness rates were 68.3% and 92.3%, respectively. The threshold value of TD to predict RIT efficacy was 70.2 Gy, based on ROC analysis. Univariate analysis showed that 24-h RAIU, Teff, total iodine dose, iodine dose per gram of thyroid tissue, TD, and thyrotropin receptor antibody level were significantly associated with RIT efficacy. Multivariate analysis indicated that 24-h RAIU, total iodine dose, iodine dose per gram of thyroid tissue, and TD were significant independent predictors of RIT efficacy. CONCLUSIONS Predicting RIT efficacy from TD with a shorter Teff was feasible in GD patients, and TD above 70.2 Gy had an especially high predictive accuracy.


Assuntos
Biomarcadores Farmacológicos/análise , Doença de Graves/radioterapia , Radioisótopos do Iodo/uso terapêutico , Adulto , Relação Dose-Resposta a Droga , Feminino , Meia-Vida , Humanos , Iodo/química , Iodo/uso terapêutico , Masculino , Pessoa de Meia-Idade , Glândula Tireoide/efeitos dos fármacos , Resultado do Tratamento
15.
Molecules ; 26(21)2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34771115

RESUMO

Isoaspartate (isoAsp) is a damaging amino acid residue formed in proteins mostly as a result of spontaneous deamidation of asparaginyl residues. An association has been found between isoAsp in human serum albumin (HSA) and Alzheimer's disease (AD). Here we report on a novel monoclonal antibody (mAb) 1A3 with excellent specificity to isoAsp in the functionally important domain of HSA. Based on 1A3 mAb, an indirect enzyme-linked immunosorbent assay (ELISA) was developed, and the isoAsp occupancy in 100 healthy plasma samples was quantified for the first time, providing the average value of (0.74 ± 0.13)%. These results suggest potential of isoAsp measurements for supplementary AD diagnostics as well as for assessing the freshness of stored donor blood and its suitability for transfusion.


Assuntos
Imunoensaio/métodos , Ácido Isoaspártico/química , Albumina Sérica Humana/química , Sequência de Aminoácidos , Anticorpos Monoclonais/imunologia , Sequência de Bases , Cromatografia Líquida , Ensaio de Imunoadsorção Enzimática , Humanos , Ácido Isoaspártico/imunologia , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/imunologia , Sensibilidade e Especificidade , Albumina Sérica Humana/genética , Albumina Sérica Humana/imunologia , Espectrometria de Massas em Tandem
16.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 38(6): 1072-1080, 2021 Dec 25.
Artigo em Zh | MEDLINE | ID: mdl-34970889

RESUMO

As one of the non-invasive imaging techniques, myocardial perfusion imaging provides a basis for the diagnosis of myocardial ischemia in coronary heart disease. Aiming at the bull-eye image in myocardial perfusion imaging, this paper proposed a branching structure, which included multi-layer transposed convolution up-sampling concatenate module and four-channel weighted channels attention module, and the output results of the branch structure were fused with the output results of trunk U-Net, to achieve accurate segmentation of the cardiac ischemia missing degree in myocardial perfusion bull-eye image. The experimental results show that the multi-layer transposed convolution up-sampling concatenate module realizes the fusion of different depth feature maps, and effectively reduces the interference of the severe sparse degree which is similar to the missing degree on the segmentation. Four-channel weighted attention module can further improve the ability to distinguish between the two similar degrees and the ability to learn edge details of the targets, and retain more abundant edge details features. The experimental data came from Tianjin Medical University General Hospital, Tianjin TEDA Hospital, Tianjin First Central Hospital and Third Central Hospital. The Jaccard scores in the self-built dataset was 5.00% higher than that of U-Net. The model presented in this paper is superior to other optimized models based on U-Net, and the subjective evaluation meets the accuracy requirements for clinical diagnosis.


Assuntos
Isquemia Miocárdica , Redes Neurais de Computação , Humanos , Processamento de Imagem Assistida por Computador , Isquemia , Isquemia Miocárdica/diagnóstico por imagem , Perfusão
17.
J Nutr ; 150(5): 1259-1265, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32006008

RESUMO

BACKGROUND: The associations of different adiposity indicators and short-term adiposity change with diabetes risk are not fully elucidated. OBJECTIVE: We aimed to assess the independent and joint effects of different baseline adiposity indicators and short-term body adiposity change on the risk of type 2 diabetes. METHODS: We prospectively followed 10,419 Chinese adults aged 20-80 y in 2008-2012. Incident diabetes was diagnosed based on fasting glucose, 2-h glucose, or glycated hemoglobin (HbA1c) after an oral glucose tolerance test using the American Diabetes Association standard. Cox proportional hazard regression models were used to assess the associations of adiposity indicators and adiposity change with diabetes risk. RESULTS: During a mean follow-up of 2.8 y, we identified 805 type 2 diabetes cases. Baseline BMI, waist circumference, and waist-height ratio (WHtR) were all positively associated with diabetes risk. The area under the curve was significantly greater for waist circumference (0.624) and WHtR (0.627) than for BMI (0.608) (P <0.05). Compared with subjects with stable adiposity levels (±2 kg or ± 3 cm in changes in body weight or waist circumference) from baseline to Year 1, those subjects with the most weight gain or the most waist circumference gain had a 1.53-fold or 1.37-fold greater risk of diabetes; those with the most weight loss had a 46% lower risk of diabetes. Furthermore, regardless of baseline weight status, weight or waist circumference change in the first year was associated with diabetes risk. CONCLUSION: Abdominal adiposity indicators, waist circumference and its change, are more strongly associated with the risk of type 2 diabetes than general adiposity indicators, BMI, and changes in body weight among Chinese adults.


Assuntos
Índice de Massa Corporal , Peso Corporal , Diabetes Mellitus Tipo 2/epidemiologia , Circunferência da Cintura , Adiposidade , Adulto , Idoso , Glicemia/análise , China/epidemiologia , Jejum , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Abdominal/complicações , Fatores de Risco , Inquéritos e Questionários , Aumento de Peso
18.
Wei Sheng Yan Jiu ; 49(5): 763-768, 2020 Sep.
Artigo em Zh | MEDLINE | ID: mdl-33070821

RESUMO

OBJECTIVE: To investigate the internal exposure levels of manganese(Mn), cobalt(Co), selenium(Se) and molybdenum(Mo) in blood and urine among the general population in parts of Shaanxi Province, and thereby to analyze their population distribution characteristics. METHODS: In 2017, a total of 720 subjects of general people aged 3-79 years were recruited from 5 counties in Shaanxi Province, by stratified random sampling method, blood and urine samples were collected, and the contents of Mn, Co, Se and Mo in blood and urine samples were detected by inductively coupled plasma mass spectrometry(ICP-MS). The test result were statistically analyzed according to different genders, regions and age groups. RESULTS: Among general people in Shaanxi Province, the median of Mn in blood and urine were separately 8. 43 and 0. 60 µg/L. The median of Mn in blood among males and females were 7. 99 and 8. 81 µg/L, the difference was statistically significant(P<0. 05), the difference of blood Mn between urban and rural areas was statistically significant(P<0. 05). The median of Co in blood and urine were separately 0. 13 and 0. 17 µg/L, the median of Co in blood among males and females were 0. 12 and 0. 15 µg/L, the median of Co in urine among males and females were 0. 16 and 0. 20 µg/L, the differences were statistically significant(P<0. 05), the differences of blood Co and urine Co in urban and rural areas were statistically significant(P<0. 05). The median of Se concentration in blood and urine were separately 73. 20 and 13. 30 µg/L, the median of Se in urine among males and females were 14. 40 and 12. 40 µg/L, the difference were statistically significant(P<0. 05), the differences of blood Se and urine Se in urban and rural areas were statistically significant(P<0. 05). The median of Mo concentration in blood and urine were separately 0. 60 and 50. 40 µg/L, the median of Mo in urine among males and females were 56. 60 and 43. 00 µg/L, the difference was statistically significant(P<0. 05), the difference of blood Mo between urban and rural areas was statistically significant(P<0. 05). Within the same gender, all indexes in whole blood(except female blood Se) were statistically significant among age groups(P<0. 05). The differences of male urine Co, urine Se, urine Mo and female urine Co among age groups were statistically significant(P<0. 05). CONCLUSION: Among general population in Shaanxi Province, the Mn, Co, Se and Mo levels in blood and urine are varied by gender age and area, the blood Se level is relatively low.


Assuntos
Manganês , Selênio , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Cobalto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Molibdênio , Adulto Jovem
19.
Wei Sheng Yan Jiu ; 49(5): 769-774, 2020 Sep.
Artigo em Zh | MEDLINE | ID: mdl-33070822

RESUMO

OBJECTIVE: To analyze the pollution characteristics of polycyclic aromatic hydrocarbons(PAHs) in atmospheric PM_(2. 5) in Lianhu district and Yanta district of Xi'an City. METHODS: From 2016-2018, PM_(2. 5) samples were regularly collected at monitoring points in two districts of Xi'an City, and analyzed the content of naphthalene, acenaphthylene, fluorene, acenaphthene, phenanthrene, anthracene, fluoranthene, pyrene, chrysene, benz(a)anthracene, benzo(b)fluoranthene, benzo(k)fluoranthene, benzo(a)pyrene, dibenz(a, h)anthracene, benzo(g, h, i)perylene, indeno(1, 2, 3-cd)pyrene in the samples according to Ambient air and stationary source emissions-Determination of gas and particle-phase polycyclic aromatic hydrocarbons-High performance liquid chromatography(HJ 647-2013). The test result were analyzed and evaluated according to different years, regions and seasons. RESULTS: The median total PAHs mass concentrations(ΣPAHs) in Lianhu district and Yanta district were 11. 68 and 12. 53 ng/m~3, respectively, with no significant difference(P>0. 05). The ΣPAHs of the two districts were decreasing year by year(P<0. 05). The median ΣPAHs in Lianhu district and Yanta district were highest in winter(55. 50, 55. 61 ng/m~3) and lowest in summer(4. 62, 4. 57 ng/m~3). The top three single indicators of the median PAHs in Lianhu district were benz(b)fluoranthene(1. 90 ng/m~3), benzo(g, h, i)perylene(1. 67 ng/m~3) and chrysene(1. 34 ng/m~3), In Yanta district, they were benz(b)fluoranthene(1. 95 ng/m~3), benzo(g, h, i)perylene(1. 63 ng/m~3) and pyrene(1. 47 ng/m~3). The average mass concentrations of benzo(a)pyrene in Lianhu district and Yanta district were 1. 33 ng/m~3 and 1. 10 ng/m~3, respectively. Among all the samples, the qualified samples of benzo(a)pyrene accounted for 72. 75% of the total samples, and the Lianhu district and Yanta district were 71. 20% and 74. 30%, respectively(P>0. 05). CONCLUSION: The degree of atmospheric PAHs pollution in Xi'an had decreased year by year, and PAHs pollution in winter was more serious.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Benzo(a)pireno , Cromatografia Líquida de Alta Pressão , Crisenos , Poluição Ambiental , Hidrocarbonetos Policíclicos Aromáticos/análise
20.
Wei Sheng Yan Jiu ; 49(3): 416-421, 2020 May.
Artigo em Zh | MEDLINE | ID: mdl-32693890

RESUMO

OBJECTIVE: To investigate the concentration levels and sources of 12 metals and metalloids in PM_(2. 5) in Lianhu district and Yanta district of Xi'an City. METHODS: From 2016-2018, PM_(2. 5) samples were collected periodically in the monitoring points of the two urban areas of Xi'an City. According to the ministry of environmental protection's "Ambient air and stationary source emission-Determination of metals in ambient particulate matter-Inductively coupled plasma/mass spectrometry"(HJ 657-2013) to determine the content of 12 metals and metalloid elements(Sb, Al, As, Be, Cd, Cr, Hg, Pb, Mn, Ni, Se, Ti). To analyse and evaluate of As, Cd, Pb and Hg according to the annual average reference concentration limit of "Ambient air quality standards"(GB 3095-2012). The main sources of 12 metals and metalloid elements were identified by enrichment factor(EF) and factor analysis. RESULTS: The total qualified rates of As, Cd, Pb and Hg were 46. 89%, 83. 03%, 99. 00% and 100. 00%, respectively, and the difference between the years was not statistically significant(P>0. 05). The average concentration of 12 metals and metalloid elements in PM_(2. 5) for three years was as follows: Al>Pb>Mn>As>Se>Sb>Cr>Cd>Ti>Ni>Hg>Be. The average concentration of As was 10. 10 ng/m~3, which was 1. 68 times exceeding the standard. The average concentration of Cd was 2. 68 ng/m~3, and the average concentration of Pb was 81. 26 ng/m~3. Concentration levels of As, Cd and Pb were on the decline. The EF values of Al, Cr, and Ni were all ≤1, the EF value of As was between 1 and 10. The EF values of Sb, Pb and Ti were all >10, and the EF values of Cd and Se were all >300. The main components of each year from 2016 to 2018 were 2, 2 and 3 respectively. The main component 1 included Pb, As, Cd, Se, Sb and Mn, and the main component 2 included Al, Cr and Ni. In 2018, the main component 3 included Ti(Ti was located in the main component 1 in 2016 and 2017). CONCLUSION: The sources of pollution of metals and metalloid elements in PM_(2. 5) in the atmosphere of Xi'an City mainly include motor vehicle emissions, coal combustion, industrial pollution and natural particles.


Assuntos
Poluentes Atmosféricos/análise , Metaloides , Metais Pesados/análise , Cidades , Monitoramento Ambiental , Metais/análise , Material Particulado/análise
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