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Acute myeloid leukemia (AML) can manifest as de novo AML (dn-AML) or secondary AML (s-AML), with s-AML being associated with inferior survival and distinct genomic characteristics. The underlying reasons for this disparity remain to be elucidated. In this multicenter study, next-generation sequencing (NGS) was employed to investigate the mutational landscape of AML in 721 patients from June 2020 to May 2023.Genetic mutations were observed in 93.34% of the individuals, with complex variations (more than three gene mutations) present in 63.10% of them. TET2, ASXL1, DNMT3A, TP53 and SRSF2 mutations showed a higher prevalence among older individuals, whereas WT1 and KIT mutations were more commonly observed in younger patients. BCOR, BCORL1, ZRSR2, ASXL1 and SRSF2 exhibited higher mutation frequencies in males. Additionally, ASXL1, NRAS, PPMID, SRSF2, TP53 and U2AF1 mutations were more common in patients with s-AML, which PPM1D was more frequently associated with therapy-related AML (t-AML). Advanced age and hyperleukocytosis independently served as adverse prognostic factors for both types of AML; however, s-AML patients demonstrated a greater number of monogenic adverse prognostic factors compared to dn-AML cases (ASXL1, PPM1D, TP53 and U2AF1 in s-AML vs. FLT3, TP53 and U2AF1 in dn-AML). Age and sex-related gene mutations suggest epigenetic changes may be key in AML pathogenesis. The worse prognosis of s-AML compared to dn-AML could be due to the older age of s-AML patients and more poor-prognosis gene mutations. These findings could improve AML diagnosis and treatment by identifying potential therapeutic targets and risk stratification biomarkers.
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First-principles crystal structure prediction (CSP) is the most powerful approach for materials discovery, enabling the prediction and evaluation of properties of new solid phases based only on a diagram of their underlying components. Here, we present the first CSP-based discovery of metal-organic frameworks (MOFs), offering a broader alternative to conventional techniques, which rely on geometry, intuition, and experimental screening. Phase landscapes were calculated for three systems involving flexible Cu(II) nodes, which could adopt a potentially limitless number of network topologies and are not amenable to conventional MOF design. The CSP procedure was validated experimentally through the synthesis of materials whose structures perfectly matched those found among the lowest-energy calculated structures and whose relevant properties, such as combustion energies, could immediately be evaluated from CSP-derived structures.
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Profound understanding of fouling behaviors and underlying mechanisms is fundamentally important for fouling control in membrane-based environmental applications. Therefore, it entails novel noninvasive analytical approaches for in situ characterizing the formation and development of membrane fouling processes. This work presents a characterization approach based on hyperspectral light sheet fluorescence microscopy (HSPEC-LSFM), which is capable of discriminating various foulants and providing their 2-dimensional/3-dimensional spatial distributions on/in membranes in a label-free manner. A fast, highly sensitive and noninvasive imaging platform was established by developing a HSPEC-LSFM system and further extending it to incorporate a laboratory-scale pressure-driven membrane filtration system. Hyperspectral data sets with a spectral resolution of â¼1.1 nm and spatial resolution of â¼3 µm as well as the temporal resolution of â¼8 s/plane were obtained, and the fouling formation and development process of foulants onto membrane surfaces, within the pores and on the pore walls were clearly observed during the ultrafiltration of protein and humic substances solutions. Pore blocking/constriction at short times while cake growth/concentration polarization at longer times was found to have coupled effects for the flux decline in these filtration tests, and yet the contribution of each effect as well as the transition of the governing mechanisms was found distinct. These results demonstrate in situ label-free characterization of membrane fouling evolution with the recognition of foulant species during filtration and provide new insights into membrane fouling. This work offers a powerful tool to investigate dynamic processes for a wide range of membrane-based explorations.
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Ultrafiltração , Purificação da Água , Purificação da Água/métodos , Membranas Artificiais , Filtração/métodos , Substâncias Húmicas , Imagem ÓpticaRESUMO
Lower temperature leads to a higher probability of visiting low-energy states. This intuitive belief underlies most physics-inspired strategies for addressing hard optimization problems. For instance, the popular simulated annealing (SA) dynamics is expected to approach a ground state if the temperature is lowered appropriately. Here, we demonstrate that this belief is not always justified. Specifically, we employ the cavity method to analyze the minimum strong defensive alliance problem and discover a bifurcation in the solution space, induced by an inflection point in the entropy-energy profile. While easily accessible configurations are associated with the lower-free-energy branch, the low-energy configurations are associated with the higher-free-energy branch within the same temperature range. There is a discontinuous phase transition between the high-energy configurations and the ground states, which generally cannot be followed by SA. We introduce an energy-clamping strategy to obtain superior solutions by following the higher-free-energy branch, overcoming the limitations of SA.
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BACKGROUND AND AIM: Thiazolidinediones (TZDs) can improve hepatic steatosis in nonalcoholic steatohepatitis (NASH). Angiotensin (Ang) II, the primary effector of renin-angiotensin system (RAS), plays vital roles in the development and progression of NASH. And some AngII-mediated effects can be regulated by TZDs. Angiotensin-converting enzyme (ACE) 2, a new component of RAS, can degrade Ang II to attenuate its subsequent physiological actions. We aimed to evaluate the effects of TZDs on ACE2 expression in insulin-sensitive tissues in NASH rats. METHODS: Forty rats were divided into the normal control, high-fat diet (HFD), pioglitazone control, and HFD plus pioglitazone groups. After 24 weeks of treatment, we evaluated changes in liver histology and tissue-specific ACE2 expression. RESULTS: ACE2 gene and protein expression was significantly greater in liver and adipose tissue in the HFD group compared with normal control group, while was significantly reduced in skeletal muscle. Pioglitazone significantly reduced the degree of hepatic steatosis compared with the HFD group. Pioglitazone significantly increased ACE2 protein expression in liver, adipose tissue, and skeletal muscle compared with the HFD group. CONCLUSIONS: Pioglitazone improves hepatic steatosis in the rats with HFD-induced NASH and upregulates ACE2 expression in insulin-sensitive tissues.
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Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/metabolismo , Resistência à Insulina/fisiologia , Peptidil Dipeptidase A/biossíntese , Tiazolidinedionas/farmacologia , Regulação para Cima/fisiologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Enzima de Conversão de Angiotensina 2 , Animais , Fígado Gorduroso/tratamento farmacológico , Fígado Gorduroso/etiologia , Regulação Enzimológica da Expressão Gênica , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Masculino , Hepatopatia Gordurosa não Alcoólica , Pioglitazona , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Tiazolidinedionas/uso terapêutico , Regulação para Cima/efeitos dos fármacosRESUMO
OBJECTIVE: Angiotensin II, one component of renin-angiotensin system (RAS), is formed from Ang I by the catalysing of angiotensin converting enzyme (ACE). Angiotensin II plays an important role in the development of insulin resistance. ACE2, a homologue of ACE, couterregulate the actions of angiotensin II by facilitating its breakdown to angiotensin-(1-7). RAS has been implicated in the pathogenesis of non-alcoholic steatohepatitis (NASH). Earlier demonstration that thiazolidinediones (TZDs) improve steatohepatitis promoted us to evaluate the change of hepatic ACE2 expression in rats with high fat diet (HFD)-induced NASH and the effects of TZDs on the hepatic ACE2 expression. MATERIAL AND METHODS: Rats were divided into normal control group, high fat diet (HFD) group, and pioglitazone group. After 24 weeks of treatment with pioglitazone, a TZD, we evaluated changes in liver histology, insulin sensitivity, lipid metabolism, circulating RAS levels and hepatic ACE2 expression. RESULTS: Compared with normal controls, the concentrations of serum lipid, aminotransaminase, glucose, insulin, ACE, angiotensin II, ACE2, angiotensin-(1-7) and the degree of hepatic ACE2 expression were significantly higher in rats with HFD-induced NASH. Pioglitazone significantly reduced the concentrations of serum lipid, aminotransaminase, glucose, insulin, ACE, angiotensin II while markedly raised the concentrations of serum ACE2, angiotensin-(1-7) and the degree of hepatic ACE2 expression. CONCLUSION: Hepatic ACE2 expression markedly increased in rats with HFD-induced NASH and was further upregulated by pioglitazone. Hepatic ACE2 may be a new target of pioglitazone treatment for NASH.
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Fígado Gorduroso/tratamento farmacológico , Fígado/efeitos dos fármacos , Peptidil Dipeptidase A/metabolismo , Sistema Renina-Angiotensina/efeitos dos fármacos , Tiazolidinedionas/farmacologia , Enzima de Conversão de Angiotensina 2 , Animais , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Dieta Hiperlipídica , Modelos Animais de Doenças , Fígado Gorduroso/sangue , Fígado Gorduroso/enzimologia , Fígado Gorduroso/etiologia , Fígado Gorduroso/genética , Insulina/sangue , Lipídeos/sangue , Fígado/enzimologia , Masculino , Peptidil Dipeptidase A/genética , Pioglitazona , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Regulação para CimaRESUMO
We report the first experimental and theoretical evaluation of the thermodynamic driving force for the reaction of metal-organic framework (MOF) materials with carbon dioxide, leading to a metal-organic carbonate phase. Carbonation upon exposure of MOFs to CO2 is a significant concern for the design and deployment of such materials in carbon storage technologies, and this work shows that the formation of a carbonate material from the popular SOD-topology framework material ZIF-8, as well as its dense-packed dia-topology polymorph, is significantly exothermic. With knowledge of the crystal structure of the starting and final phases in the carbonation reaction, we have also identified periodic density functional theory approaches that most closely reproduce the measured reaction enthalpies. This development now permits the use of advanced theoretical calculations to calculate the driving forces behind the carbonation of zeolitic imidazolate frameworks with reasonable accuracy.
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The application of Hirshfeld atom refinement (HAR) fragmentation is demonstrated for the refinement of metal-organic framework (MOF) crystal structures. The presented method enables anisotropic refinement of imidazolate hydrogen atoms, as well as complex analysis of solvent disorder within MOF pores. The data used were derived from standard resolution in-house single crystal X-ray diffraction measurements, demonstrating that high quality structural analysis of MOFs no longer requires access to neutron or synchrotron facilities.
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Hidrogênio , Estruturas Metalorgânicas , Difração de Raios X , Hidrogênio/química , Cristalografia por Raios X , SíncrotronsRESUMO
Thiazolidinediones (TZDs) markedly reduce hepatic steatosis in both rodents and humans. However, the effects and mechanisms of action of TZDs on hepatic fibrosis remain unclear. The aim of the present study was to determine the effects of TZDs on histological changes in the liver and on the modulation by adiponectin via the AMP-activated protein kinase (AMPK) signalling pathway in rats with non-alcoholic steatohepatitis (NASH). Forty rats were divided into normal control, high-fat diet (HFD), pioglitazone control and pioglitazone intervention groups. After 24 weeks treatment with pioglitazone (10 mg/kg per day by gavage), changes in liver histology, serum aminotransaminase, triglyceride (TG), free fatty acid (FFA), glucose, insulin, adiponectin and transforming growth factor (TGF)-ß1 concentrations and hepatic adiponectin, AMPK, α-smooth muscle actin (α-SMA) and collagen I expression were evaluated. The degree of hepatic steatosis and fibrosis was significantly higher in HFD-induced NASH rats compared with normal controls, as were serum concentrations of aminotransaminase, TG, FFA, glucose, insulin and TGF-ß1 and hepatic expression of α-SMA and collagen I protein. Serum adiponectin concentrations and hepatic expression of adiponectin mRNA and AMPK protein were significantly lower in the HFD-induced NASH rats compared with the normal control. Pioglitazone significantly reduced the degree of hepatic steatosis and fibrosis, as well as serum concentrations of aminotransaminase, TG, FFA, glucose, insulin and TGF-ß1 and hepatic expression of α-SMA and collagen I protein. In addition, pioglitazone significantly increased serum adiponectin concentrations and hepatic expression of adiponectin mRNA and AMPK protein. In conclusion, the TZD pioglitazone improved hepatic fibrosis in rats with NASH by upregulating adiponectin expression and activating AMPK, thus subsequently inhibiting the activation of hepatic stellate cells and the overproduction of extracellular matrix.
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Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Fígado Gorduroso/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Cirrose Hepática/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Tiazolidinedionas/uso terapêutico , Animais , Peso Corporal/efeitos dos fármacos , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/complicações , Fígado Gorduroso/enzimologia , Fígado Gorduroso/patologia , Hipoglicemiantes/administração & dosagem , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/patologia , Cirrose Hepática/enzimologia , Cirrose Hepática/etiologia , Cirrose Hepática/patologia , Testes de Função Hepática , Masculino , Hepatopatia Gordurosa não Alcoólica , Tamanho do Órgão/efeitos dos fármacos , Pioglitazona , Ratos , Ratos Sprague-Dawley , Tiazolidinedionas/administração & dosagemRESUMO
The Istiodactylidae is a group of pterodactyloids characterised by large nasoantorbital fenestrae and labiolingually compressed teeth, with several records reported from the Early Cretaceous of northeastern China and western Europe. Here we report a new istiodactylid, Lingyuanopterus camposi gen. et sp. nov. from the Jiufotang Formation of Lingyuan, Liaoning, northeastern China. The holotype is represented by a near-complete skull, mandible and atlas-axis complex. It is distinguished from other istiodactylids by several characters, including two autapomorphies: short triangular tooth crowns with sharp mesial and distal carinae limited to the distal teeth, mandibular symphysis occupying approximately a quarter the mandible length. We also report the presence of helical jaw joints in istiodactylids, and provide a revised diagnosis of the clade Istiodactylidae, which includes five genera: Istiodactylus, Liaoxipterus, Nurhachius, Luchibang and Lingyuanopterus. Four pellets containing fish fragments were observed and are tentatively interpreted as bromalites of Lingyuanopterus. Although members of this clade possess similar skull morphologies, istiodactylids vary in terms of their dentition, with at least three forms from the Jiufotang Formation alone. This may represent different feeding strategies, and also indicate a similarity between the pterosaur assemblages of northeastern China and Britain during the Early Cretaceous.
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Dinossauros , Animais , Filogenia , Dinossauros/anatomia & histologia , Fósseis , China , Articulação TemporomandibularRESUMO
Probabilistic message-passing algorithms are developed for routing transmissions in multiwavelength optical communication networks, under node- and edge-disjoint routing constraints and for various objective functions. Global routing optimization is a hard computational task on its own but is made much more difficult under the node- and edge-disjoint constraints and in the presence of multiple wavelengths, a problem which dominates routing efficiency in real optical communication networks that carry most of the world's internet traffic. The scalable principled method we have developed is exact on trees but provides good approximate solutions on locally treelike graphs. It accommodates a variety of objective functions that correspond to low latency, load balancing, and consolidation of routes and can be easily extended to include heterogeneous signal-to-noise values on edges and a restriction on the available wavelengths per edge. It can be used for routing and managing transmissions on existing topologies as well as for designing and modifying optical communication networks. Additionally, it provides the tool for settling an open and much-debated question on the merit of wavelength-switching nodes and the added capabilities they provide. The methods have been tested on generated networks such as random-regular, Erdos Rényi, and power-law graphs, as well as on optical communication networks in the United Kingdom and United States. They show excellent performance with respect to existing methodology on small networks and have been scaled up to network sizes that are beyond the reach of most existing algorithms.
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A 2 : 1 urea â adipic acid cocrystal was obtained in two polymorphic forms (Form I reported earlier, and Form II synthesized in this study) using mechanochemistry as well as solution crystallization. Lower solubility and leaching study showed the newly synthesized urea â adipic acid 2 : 1 cocrystal to be an efficient sustained-release nitrogen fertilizer compared to commercially available urea.
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Nitrogênio , Ureia , Adipatos , Preparações de Ação Retardada , SolubilidadeRESUMO
PURPOSE: We seek to confirm the safety and efficacy of percutaneous fine needle aspiration biopsy (FNAB) for small renal masses (SRMs) without chance of nephron-sparing surgery (NSS). METHODS: Between 2015 and 2018, 169 consecutive patients with SRMs treated in two medical centers were enrolled in the study retrospectively. All patients were evaluated to be candidates of radical nephrectomy (RN) at the initial evaluation preoperatively and they would receive the second evaluation in operation to decide the ultimate surgical regimen. Patients were divided into two groups according to FNAB. RESULTS: 169 patients met inclusion criteria were enrolled in the finial study. The median follow-up of was 35 months (ranges from 23 to 49 months) from the first diagnosis. 83 patients received FNAB before surgery, and the other 86 patients underwent surgery immediately. The initial success rate of FNAB was 91.6% (76/83) and the rate of accuracy in identifying malignancies was 100%. 15 (18.1%) of 83 patients developed different levels of complications. 15 (18.1%) were diagnosed as benign tumors by FNAB. The initial success rate was just 50% for cystic SRMs. Complicated cystic SRMs account for 5.9% of all with a 50% benignity rate. The FNAB group had a significant lower ratio of RN than non-FNAB group (74.7% vs. 93%, p = 0.001, Pearson Chi-square test). CONCLUSION: FNAB is safe and effective for SRMs without chance of NSS, and it could significantly reduce unnecessary RN.
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Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Adulto , Idoso , Biópsia por Agulha Fina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrectomia/métodos , Néfrons , Tratamentos com Preservação do Órgão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Studies suggested that hypertension was associated with impaired health-related quality of life and it is important to find a proper and feasible management of hypertension in the community. This study evaluates the effect of a tailored target intervention on influence factors of quality of life in Chinese patients with hypertension. A cross-sectional survey was carried out to investigate 644 patients with hypertension by using the Chinese version of the short form-36, and 195 patients were screened out to participate in the tailored target intervention. Multivariate linear regression analyses showed that age, gender, educational level, high intake of fried food, household income, attitude, knowledge, blood pressure, symptoms, serious events during the past year, duration of hypertension, and number of taking anti-hypertensive medicine were significantly correlated with quality of life. Grade-based management by community physicians and physical exercise had a positive effect on quality of life. After the 6-month intervention, the control rate of hypertension was increased from 32.0% to 39.4%, and the mean systolic and diastolic blood pressure values were significantly decreased to 137.2 and 85.7 mmHg vs. 140.9 and 87.6 mmHg at baseline, respectively. The intervention program resulted in overall improvement on total score of quality of life and mean scores of all the domains except social functioning in patients with hypertension. In view of the influence factors of quality of life, taking the tailored target intervention could not only improve the quality of life of hypertensive patients, but also effectively increase the control rate of hypertension.
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Hipertensão/fisiopatologia , Hipertensão/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , China , Estudos Transversais , Exercício Físico , Feminino , Humanos , Hipertensão/psicologia , Masculino , Pessoa de Meia-Idade , Qualidade de VidaRESUMO
OBJECTIVE: To investigate the effects of 4 renin-angiotensin system's(RAS) regulators (losartan, telmisartan, aliskiren and angiotenisin) on the human leukemia HEL cell growth. METHODS: The HEL cells were treated with losartan, telmisartan, aliskiren and Angiotensin-(1-7) (Ang-(1-7)) for 12 days, respectively. The cell proliferation was measured by CCK-8 kit, the cell cycle and apoptosis were measured by flow cytometry. RESULTS: The 10-7 mol/L Ang-(1-7) markedly inhibited the growth of HEL cells, blocked cells at G0/G1 phase and markedly increased the late apoptotic cells (P< 0.001). The 10-5 mol/L losartan and telmisartan, 10-4 mol/L aliskiren had no effects on the proliferation, cell cycle and apoptosis of HEL cells (P>0.05). CONCLUSION: Ang-(1-7), one of renin-angiotensin system's regulators, can inhibit the growth of HEL cells and promote the cell apoptosis. Ang-(1-7) may be one potential therapeutic drug for polycythemia vera with JAK2 mutation.
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Leucemia , Proliferação de Células , Humanos , Losartan , Policitemia Vera , Sistema Renina-AngiotensinaRESUMO
Patients with unresectable advanced soft-tissue sarcomas (STS) receiving radiotherapy or/and chemotherapy still have a poor prognosis. This study aimed to evaluate retrospectively the efficacy and safety of recombinant adenovirus-p53 (rAd-p53) gene therapy combined with radiotherapy and hyperthermia for advanced STS. A total of 71 patients with advanced unresectable STS treated at the authors' center from April 2007 to November 2014 were included. Of these 71 patients, 36 cases received rAd-p53 therapy combined with radiotherapy and hyperthermia (p53 group), while 35 cases received radiotherapy and hyperthermia alone (control group). Short-term therapeutic efficacies, long-term survival outcomes, and adverse events were evaluated and compared between groups. Compared to the control group, the p53 group had a significantly higher disease control rate (83.33% vs. 54.29%; p = 0.008) and a lower progressive disease rate (16.67% vs. 45.71%; p = 0.018). In addition, rAd-p53 treatment significantly improved the progression-free survival and overall survival of STS patients. Cox regression indicated that rAd-p53 treatment significantly reduced the risks for disease progression or death event for STS patients. Furthermore, there was no significant difference in all adverse events, except for transient fever, which occurred in 89% of patients with rAd-p53 therapy. rAd-p53 combined with radiotherapy and hyperthermia can effectively improve the therapeutic efficacy and survival outcomes in patients with advanced unresectable STS, providing a new therapeutic strategy.
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Adenoviridae/genética , Terapia Genética , Recombinação Genética , Sarcoma/genética , Sarcoma/terapia , Proteína Supressora de Tumor p53/genética , Adolescente , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Terapia Genética/efeitos adversos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Proteína Supressora de Tumor p53/metabolismo , Adulto JovemRESUMO
OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is a condition associated with type 2 diabetes (T2D). Insulin resistance, a common pathogenesis of NAFLD and T2D, is partially caused by alterations in angiotensin II (Ang II) and is accompanied by hypoadiponectinemia. We aimed to investigate whether the circulating Ang II and adiponectin concentrations are related to hyperglycemia in male NAFLD patients. METHODS: Thirty-five controls and 85 NAFLD patients without prior known T2D were enrolled. All participants were non-smoking men who performed 75-g oral glucose tolerance tests. According to the American Diabetes Association (ADA) criteria, the NAFLD patients were divided into the euglycemia and hyperglycemia groups. The NAFLD patients with hyperglycemia were further divided into the isolated impaired fasting glucose (I-IFG) and postprandial hyperglycemia subgroups. The fasting serum Ang II and adiponectin concentrations were measured. RESULTS: Among the 85 NAFLD patients, 40 (47%) had hyperglycemia, including I-IFG (18%) and postprandial hyperglycemia (29%). The serum Ang II concentrations in the euglycemia and hyperglycemia groups were significantly higher than those observed in the control and euglycemia groups, respectively; whereas the serum adiponectin concentrations were significantly lower. The serum Ang II concentrations were significantly higher in the postprandial hyperglycemia subgroup than in the I-IFG subgroup. The serum Ang II and adiponectin concentrations were found to be independent predictors of hyperglycemia in the NAFLD patients. The serum Ang II concentration was significantly associated with the serum adiponectin and 2-hour postprandial glucose concentrations in the NAFLD patients. CONCLUSION: An increased circulating Ang II concentration is associated with hypoadiponectinemia and postprandial hyperglycemia in male NAFLD patients and may be involved in the pathogenesis of T2D in NAFLD patients.
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Adiponectina/deficiência , Angiotensina II/sangue , Circulação Sanguínea/fisiologia , Fígado Gorduroso/sangue , Hiperglicemia/sangue , Erros Inatos do Metabolismo/sangue , Adiponectina/sangue , Adulto , Biomarcadores/sangue , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/epidemiologia , Humanos , Hiperglicemia/diagnóstico , Hiperglicemia/epidemiologia , Masculino , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/epidemiologia , Pessoa de Meia-Idade , Hepatopatia Gordurosa não AlcoólicaRESUMO
OBJECTIVE: To observe the therapeutic efficacy of 131I-labeled granulocyte macrophage colony-stimulating factor (GM-SCF) in SCID mouse-acute myeloid leukemia model, and the relationship between dose and effect. METHODS: SCID-mouse acute myeloid leukemia model was established by injecting HL-60 cells through tail vein. GM-CSF was labeled with 131I by the chloramines-T method. SCID mice were randomly divided into 6 groups. Groups I, II and III treatment groups were given 9.25 x 10(5), 22.20 x 10(5) and 37.00 x 10(5) Bq of 131I-GM-CSF, respectively. Group IV was given 131I. Group V was given blending of 131I and GM-CSF. Group VI was control. Changes of HL-60 cells in blood and marrow, as well as white blood cells, red blood cells and platelets in blood were detected. Survival time of the SCID mice was calculated. RESULT: It was observed that WBC, HL-60 cells in blood and marrow were less in treatment groups than that in control groups, especially in groups II, III. After 2 weeks of treatment, BPC of II, III groups increased remarkably (P < 0.01). Survival time of the SCID mice was prolonged in treatment groups (P < 0.01), especially in group III, the longest survival time of 60 days. CONCLUSION: 131I-GM-CSF could increase leukemic SCID mice survival rate. The therapeutic efficacy of low dose and mediate dose of 131I-GM-CSF is dose-dependent. 131I-GM-CSF is an effective radiation immunity therapy for leukemic mice.
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Antineoplásicos/uso terapêutico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Animais , Relação Dose-Resposta a Droga , Feminino , Células HL-60 , Humanos , Camundongos , Camundongos SCID , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To investigate the biodistribution of 131I-GM-CSF in SCID mice bearing human AML in vivo. METHODS: The xenograft model of human leukemia was established in SCID mice. In the leukemia mice, the biodistribution of 131I-GM-CSF produced by chlo amine-T method was studied. RESULTS: (1)The inoculated HL-60 cells could grow in SCID mice, which developed leukemia after 4 weeks. (2) 131 I-GM-CSF was concentrated in spleen, bone marrow and tumor tissue of the mice. In spleen and bone marrow, 131 I-GM-CSF was uptaken to peak in 30 minutes after injection, the up taking rate was (442. 9+/-86. 4) % ID/g and (4283. 8+/-252. 8)% ID/g, respectively, and maintained on higher level in 24 hours. The injection of 131I resulted in an even distribution in the whole body. CONCLUSIONS: 131 I-GM-CSF is able to concentrate electively in spleen, bone marrow and organs infiltrated by leukemia cells. The biodistribution of 131I-GM-CSF in the leukemia mice is tissue specific.