Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 57
Filtrar
1.
J Med Virol ; 95(1): e28294, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36367155

RESUMO

The global monkeypox outbreak in 2022 has severely affected the life and health of people. Currently, partial smallpox vaccines have been approved for monkeypox prevention. Considering the potential occupational health risks of monkeypox infection among healthcare workers (HCWs), this study explored the willingness of Chinese HCWs to receive the monkeypox vaccine and analyzed the factors influencing their decision. We conducted an online cross-sectional survey among HCWs of 10 Chinese hospitals from May 30th, 2022 to August 1st, 2022. Specifically, a self-report questionnaire was administered to evaluate the attitude and acceptance of HCWs toward the monkeypox vaccine, followed by a multivariate logistic regression analysis to determine the independent predictors of vaccination. The survey included 1032 participants, of whom 90.12% expressed their willingness for vaccination (vaccine hesitancy rate = 9.88%). Univariate analysis showed that 11 variables differed significantly between the vaccine acceptance and vaccine hesitancy groups. Multivariate logistic regression analysis demonstrated that the age of 30-40 years (odds ratio [OR] = 0.504, 95% confidence interval [CI]: 0.284-0.893, p = 0.019 vs. age of <30 years old), working in a secondary hospital (OR = 0.449, 95% CI: 0.249-0.808, p = 0.019 vs. working in a tertiary hospital), considering vaccination necessary for controlling monkeypox infection (OR = 4.135, 95% CI: 2.109-8.106, p < 0.001 vs. not considering it necessary), willingness to pay for the monkeypox vaccine (OR = 2.125, 95% CI: 1.206-3.745, p = 0.009 vs. no willingness to pay), considering implementation of mandatory vaccination necessary (OR = 1.990, 95% CI: 1.023-3.869, p = 0.043 vs. not considering it necessary), and recommending family members and friends to take the vaccine (OR = 13.847, 95% CI: 7.487-25.609, p < 0.001 vs. not recommending) were crucial independent predictors of the willingness to receive monkeypox-related vaccination. This study evaluated the acceptance and hesitancy rates of Chinese HCWs toward the monkeypox vaccine and found that the willingness to receive vaccination was mainly correlated to age, hospital level, and attitude toward vaccination. Therefore, to promote vaccine absorption, we recommend expanding publicity, formulating reasonable policies, and improving the recognition of vaccines.


Assuntos
Mpox , Vacina Antivariólica , Vacinas , Humanos , Adulto , Estudos Transversais , Mpox/prevenção & controle , Vacinação , Pessoal de Saúde , Centros de Atenção Terciária
2.
Chin Med Sci J ; 38(3): 218-227, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37376890

RESUMO

Objective To analyze the medication rules of traditional Chinese medicine (TCM) for malaria treatment.Methods Statistical analysis was conducted on the basic attributes of TCM drugs with regard to property, therapeutic methods, flavor, and meridian tropism. A complex network of TCM drug associations was constructed. Cluster analysis was applied to obtain the core drugs for malaria treatment. The Apriori algorithm was applied to analyze the association rules of these core drugs.Results A total of 357 herbs were used 3,194 times in 461 prescriptions for malaria treatment. Radix Glycyrrhizae (), Rhizoma Pinelliae (), Radix Bupleuri (), and Radix Dichroae () were the frequently used herbs through supplementing, exterior-releasing, heat-clearing, qi-rectifying, and damp-resolving therapeutic methods. Such herbs had warm, natural, and cold herbal properties; pungent, bitter, and sweet flavors; and spleen, lung, and stomach meridian tropisms. Cluster analysis showed 61 core drugs, including Radix Glycyrrhizae, Rhizoma Pinelliae, Radix Bupleuri, and Radix Scutellariae (). Apriori association rule analysis yielded 12 binomial rules (herb pairs) and 6 trinomial rules (herb combinations). Radix Bupleuri plus Radix Scutellariae was the core herbal pair for treating malaria. This pair could be combined with Rhizoma Atractylodis Macrocephalae () for treating warm or cold malaria, combined with Pericarpium Citri Reticulatae () or Radix Dichroae () for treating miasmic malaria, or combined with turtle shells () for treating malaria with splenomegaly.Conclusions TCM can be used to classify and treat malaria in accordance with the different stages of development. As the core herbal pair, Radix Bupleuri and Radix Scutellariae can be combined with other drugs to treat malaria with different syndrome types.


Assuntos
Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Medicamentos de Ervas Chinesas/uso terapêutico , Mineração de Dados
3.
Oral Dis ; 27(6): 1376-1382, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32497401

RESUMO

Malaria is a worldwide parasitic disease, which affects millions of lives every year. Various medications are recommended by WHO for prevention and treatment of malaria. However, adverse events caused by antimalarials were frequently reported, some of which were severe and fatal. Disorders of many organs related to antimalarials have been well recognized, whereas few studies concentrated on the relationship between antimalarials and oral-maxillofacial system health. Current review generalized the relevance of antimalarials to the health of oral-maxillofacial part and raised an urgent need to form a standard management for antimalarial-related oral-maxillofacial adverse events.


Assuntos
Antimaláricos , Malária , Antimaláricos/efeitos adversos , Humanos , Malária/tratamento farmacológico , Índice de Gravidade de Doença
4.
Neoplasma ; 68(4): 892-898, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34034497

RESUMO

Survival rates are usually used to evaluate the effect of cancer treatment and prevention. No study has focused on the characteristic of population-based cancer survival in Fujian, which is regarded as one of the high-risk areas of cancer in China. This study aims to analyze the 5-year relative survival of patients in Fujian Province using population-based cancer registry data. A total of 8 population-based registries in Fujian Province reported cancer cases diagnosed in 2012-2014. Relative survival was calculated as the ratio between observed survival and expected survival. The 5-year relative survival for all cancers combined was 36.19% and the age-standardized 5-year relative survival for all patients was 31.80%. Females had higher relative survival than males (38.90% and 27.00%). The patients in urban areas had higher relative survival than those in rural areas (32.34% and 31.29%). Lung, gastric, liver, colorectal, and esophageal cancers were the five most common cancers, with 5-year relative survival below 50%. This is the first study that evaluated the population-based cancer relative survival in Fujian, China. Our study suggests that the overall survival of cancer patients in Fujian Province is poor. Furthermore, the results of this study can be used as a baseline for further research in Fujian, and provide important evidence for cancer etiology research.


Assuntos
Neoplasias Esofágicas , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Sistema de Registros , Taxa de Sobrevida
5.
J Sci Food Agric ; 101(4): 1589-1597, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32869870

RESUMO

BACKGROUND: Ginkgotoxin including 4'-O-methylpyridoxine (MPN) and MPN-5'-glucoside (MPNG) is responsible for Ginkgo seed food poisoning. The purpose of the work reported was to prepare detoxified Ginkgo seed powder and at the same time to retain the nutritional and functional components of Ginkgo seed powder to the maximum extent. RESULTS: Resin adsorption technology was firstly employed to remove ginkgotoxin from water extract of Ginkgo seed powder. Under optimal conditions, the adsorption efficiency of the optimal resin for MPN could reach 100%, and that for MPNG could only reach 85.4 ± 0.93%. Resin adsorption alone could not effectively remove MPN and MPNG simultaneously. Endogenous enzymatic hydrolysis was next attempted to transform MPNG to MPN. MPNG could be completely hydrolyzed to MPN by endogenous enzyme(s) at 40 °C and pH 5.0 in 180 min. Ginkgotoxin only in the form of MPN in the enzymatic hydrolysate was then adsorbed with resin and the conditions were statistically optimized. The adsorption efficiency of MPN reached 98.89 ± 0.99% under the optimized conditions. CONCLUSIONS: Removal of ginkgotoxin by combining endogenous enzymatic hydrolysis with resin adsorption could preserve the main nutritional and functional components of Ginkgo seed powder to the most extent, and did not change its main characteristics. The ginkgotoxin removal method developed in this work is a relatively simple and efficient approach. © 2020 Society of Chemical Industry.


Assuntos
Manipulação de Alimentos/métodos , Ginkgo biloba/química , Proteínas de Plantas/metabolismo , Sementes/toxicidade , Adsorção , Manipulação de Alimentos/instrumentação , Ginkgo biloba/enzimologia , Ginkgo biloba/toxicidade , Temperatura Alta , Hidrólise , Pós/química , Pós/toxicidade , Piridoxina/análogos & derivados , Piridoxina/química , Piridoxina/toxicidade , Resinas Sintéticas/química , Sementes/química
6.
Chem Pharm Bull (Tokyo) ; 65(6): 582-585, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28381698

RESUMO

An efficient synthesis of ODM-201's diastereomers has been developed from (R)-methyl 3-hydroxybutanoate or (S)-methyl 3-hydroxybutanoate, respectively, with high overall yield and excellent diastereomeric purity. The key step in this synthesis is the preparation of the key intermediate (R)-5-(1-((tert-butyldimethylsilyl)oxy)ethyl)-1H-pyrazole-3-carboxylic acid or (S)-5-(1-((tert-butyldimethylsilyl)oxy)ethyl)-1H-pyrazole-3-carboxylic acid through intramolecular 1,3-dipolar cycloaddition of the vinyl diazo carbonyl compounds.


Assuntos
Pirazóis/química , Espectroscopia de Ressonância Magnética Nuclear de Carbono-13 , Reação de Cicloadição , Humanos , Masculino , Espectroscopia de Prótons por Ressonância Magnética , Espectrometria de Massas por Ionização por Electrospray , Estereoisomerismo
7.
Zhonghua Yi Xue Za Zhi ; 96(8): 620-4, 2016 Mar 01.
Artigo em Chinês | MEDLINE | ID: mdl-26932855

RESUMO

OBJECTIVE: To detect the expression level of growth differentiation factor 11 (GDF11) in patients with myelodysplastic syndrome (MDS), and to evaluate the relationship between GDF11 level and erythropoiesis functions. METHODS: A total of 44 MDS patients (18 low-risk group patients and 26 high-risk group patients) in Department of Hematology in Tianjin Medical University General Hospital and 10 normal controls were selected from September 2014 to June 2015. The concentration of GDF11 in peripheral blood was detected using enzyme-linked immunosorbent assay (ELISA). GDF11 mRNA expression in bone marrow mononuclear cells (BMMNC) was detected using RT-PCR method. The percentage of erythroid cells (CD235a) in bone marrow was detected by flow cytometry. The correlation between these indexes and erythropoiesis functions (including red blood cell count (RBC), hemoglobin level (Hb), hematocrit (Hct), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), reticulocyte percentage (Ret%), and proportion of nucleated eryhrocyte in bone marrow) were evaluated. RESULTS: (1) The GDF11 level in peripheral blood was significantly higher in high-risk group ((128.67±47.62) µg/L) than in low-risk group ((65.96±36.55) µg/L, P<0.01) and in normal controls ((29.76±10.10) µg/L, P<0.01), also significantly higher in low-risk group than in normal controls (P<0.05). The concentration of GDF11 in severe/moderate anemic MDS patients ((80.97±9.94) µg/L) was higher than that in normal controls/ mild anemic MDS patients((66.82±19.52) µg/L), but with no statistically significant (P>0.05). (2) The percentages of CD235a(+) cells in high-risk and low-risk groups were 38.49%±5.42% and 42.64%±7.36%, respectively, showing no statistically significant difference (P>0.05). (3) In high-risk group, the GDF11 level in peripheral blood was negatively correlated with Hb, RBC and Hct in peripheral blood (r=-0.437, -0.430, -0.306, all P<0.05), and positively correlated with nucleated eryhrocyte, Ret%, MCV and CD235a(+) cells in bone marrow (r=0.465, 0.392, 0.505, 0.387, all P<0.05), but not correlated with MCH and MCHC (both P>0.05). In low-risk group, the GDF11 level in peripheral blood was positively correlated with CD235a(+) cells in bone marrow (r=0.429, P<0.05), and not correlated with Hb, RBC, Ret%, MCHC, MCV, MCH, Hct and nucleated eryhrocyte (all P>0.05). (4) The mRNA expression of GDF11 in MDS patients (39.82±14.55) was higher than that in the controls (1.84±0.64, P<0.01). CONCLUSIONS: GDF11 level in peripheral blood is higher in patients with MDS and increases with the disease risk. The more severe the anemia, the higher the GDF11 level. It may be closely correlated with erythropoiesis indicators in MDS.


Assuntos
Síndromes Mielodisplásicas , Anemia , Medula Óssea , Células da Medula Óssea , Proteínas Morfogenéticas Ósseas , Ensaio de Imunoadsorção Enzimática , Índices de Eritrócitos , Citometria de Fluxo , Fatores de Diferenciação de Crescimento , Humanos
8.
Zhonghua Yi Xue Za Zhi ; 95(32): 2620-2, 2015 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-26711612

RESUMO

OBJECTIVE: To investigate the clinical characteristics and risk factors of monosomy 7 malignant clonal evolution in patients with severe aplastic anemia (SAA) treated with combined immunosuppressive therapy (IST). METHODS: The clinical data of SAA patients treated with IST who had monosomy 7 malignant clonal evolution from October 2004 to January 2012 were analyzed respectively. RESULTS: Six patients (4.2%) had monosomy 7 clonal evolutions. The median time to monosomy 7 was 36 (12-75) months after IST. All 6 patients were diagnosed myelodysplastic syndromes (MDS). Among them, 3 patients transformed to acute myeloid leukemia following MDS. The time was 24, 45 and 51 months after IST. The median following time was 42 (17-84) months. Four patients died during the following time. The median time from MDS to death was 9 (5-17) months. Among them, three patients died with infection, one died with cerebral hemorrhage. Six patients had the clinical characteristics that they had no response to IST after 6 months, high monocyte percentage in one month after IST combined with recombinant human granulocyte colony stimulating factor (rHu-GCSF) and agranulocytosis in 3 months after IST. CONCLUSION: Poor myeloid response to IST suggests malignant clonal hematopoiesis and poor prognosis in SAA patients.


Assuntos
Anemia Aplástica , Hematopoese , Deleção Cromossômica , Cromossomos Humanos Par 7 , Fator Estimulador de Colônias de Granulócitos , Humanos , Imunossupressores , Leucemia Mieloide Aguda , Monócitos , Proteínas Recombinantes , Fatores de Risco
11.
Zhonghua Yi Xue Za Zhi ; 94(10): 737-41, 2014 Mar 18.
Artigo em Chinês | MEDLINE | ID: mdl-24844955

RESUMO

OBJECTIVE: To analyze the percentage and functional changes of natural kill (NK) cell in peripheral blood of myelodysplastic syndrome (MDS) patients so as to evaluate the relationships between these changes and hematopoietic functions and explore the role of NK cell in the pathogenesis of MDS. METHODS: By flow cytometry, the percentage of NK cell (CD3⁻CD56⁺CD16⁺) in peripheral blood lymphocytes was detected in 20 MDS patients, 15 acute myelogenous leukemic (AML) and 15 normal controls from March 2013 to November 2013 at our hospital.NK cell activation receptors (NKG2D, NKp44), inhibitory receptors (CD158a, CD158b), perforin and granzyme-ß of patients and normal controls were also detected. The correlation between these changes and hematopoietic functions, including the percentages of neutrophil granulocyte (ANC%), lymphocyte (Lym%), reticulocyte (RET%) and hemoglobin, thrombocyte in peripheral blood and the hematopoietic function in bone marrow (CD34⁺%) were evaluated. RESULTS: (1) The percentage of NK cell (3.87% ± 0.97%) in MDS patients was significantly lower than that of normal controls (6.08% ± 1.37%, P < 0.05) and higher than that of AML patients (2.58% ± 0.78%, P < 0.05).(2) The expression of NKG2D in MDS patients (52.83%) was significantly lower than that of normal controls (86.36%, P < 0.05) and higher than that of AML patients (42.00%, P < 0.05). The expression of NKp44 in MDS patients (2.41%) was significantly higher than that of normal controls (0.62%) and AML patients (0.92%) (both P < 0.05). (3) The expression of CD158a in MDS and AML patients (5.46% ± 2.40%, 4.05% ± 1.89%) were significantly both lower than those of normal controls (7.97% ± 2.85%, both P < 0.05). The expression of CD158b had no significant difference among the 3 groups. (4) The expression of perforin in MDS patients (17.83%) was significantly lower than that of normal controls (59.79%, P < 0.05) and higher than that of AML patients (13.06%, P < 0.05). The expressions of granzyme-ß in MDS and AML patients (21.54%, 30.65%) were significantly both lower than those of normal controls (83.42%, both P < 0.05). (5) The percentage of NK cell and the expression of NKG2D and NKp44 in MDS patients with low-risk group were in turn higher than those of high-risk group (4.06% ± 0.56% vs 3.59% ± 1.37%, 53.42% ± 6.85% vs 47.29% ± 8.08%, 2.46% vs 2.07%, all P < 0.05) , the expression of CD158a and CD158b were in turn lower than those of high-risk group, but both P > 0.05.(6) The percentage of NK was positively correlated with ANC% (r = 0.780, P < 0.05), but negatively with Lym% and the CD34⁺% in bone marrow (r = -0.543, -0.610, both P < 0.05). The expression of CD158a was positively correlated with CD34⁺% in bone marrow (r = 0.612, P < 0.05). The expressions of NKp44, CD158a, perforin and granzyme-ß of NK cells had no correlation with hematopoiesis (all P > 0.05). CONCLUSION: The lowered percentage and function of NK may cause the immunological dysfunction and lead to underkill of pathological hematopoietic cells in MDS.


Assuntos
Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Granzimas/metabolismo , Humanos , Leucemia Mieloide Aguda , Masculino , Pessoa de Meia-Idade , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Receptor 2 Desencadeador da Citotoxicidade Natural/metabolismo , Perforina/metabolismo , Receptores KIR2DL3/metabolismo , Adulto Jovem
12.
Zhonghua Yi Xue Za Zhi ; 93(20): 1533-6, 2013 May 28.
Artigo em Chinês | MEDLINE | ID: mdl-24028717

RESUMO

OBJECTIVE: To explore the changes in telomere length and gene expression of complex shelterin (composed of 6 core components: TRF1, TRF2, POT1, TIN2, TPP1 and RAP1) in severe aplastic anemia (SAA). METHODS: Bone marrow samples were obtained from 20 SAA patients and 10 normal controls. CD3(+)T cells were sorted by immunomagnetic separation. Telomere length was tested by Southern blot and the gene expressions of TRF1, TRF2, POT1, TIN2, TPP1 and RAP1 were detected by reverse transcription-PCR(RT-PCR). RESULTS: Telomeres of CD3(+)T cells were found significantly shorter in SAA untreated ((4.4 ± 1.1) kb, n = 9) and recovering groups((5.8 ± 1.0) kb, n = 11) than control group ((9.2 ± 3.3) kb, P < 0.05). Telomere length of CD3(+)T cells shortened with TH/S decreasing (r = 0.564, P = 0.029). The mRNA expression of POT1 decreased in untreated SAA patients (0.16(0.02-0.29)) and over-expressed in recovering patients (1.17(0.82-1.86), P < 0.05). The mRNA expression of RAP1 was significantly higher in untreated patients (4.14 (1.93-6.92)) than that in recovering group (0.87 (0.30-1.73) ) and controls (0.62 (0.45-4.07) , both P < 0.05). CONCLUSION: Changes in telomere length and shelterin gene expression occur in CD3(+)T cells of SAA patients and may be correlated with disease severity.


Assuntos
Anemia Aplástica/metabolismo , Linfócitos T/metabolismo , Proteínas de Ligação a Telômeros/metabolismo , Telômero/metabolismo , Adolescente , Adulto , Idoso , Anemia Aplástica/genética , Complexo CD3/metabolismo , Estudos de Casos e Controles , Criança , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Complexo Shelterina , Proteínas de Ligação a Telômeros/genética , Adulto Jovem
13.
Nurs Open ; 10(6): 3906-3913, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36811165

RESUMO

AIM: The aim of this study was to establish an infection prevention and control strategy for nursing managements during surgical operations in coronavirus disease 2019 (COVID-19) patients. DESIGN: A Delphi method. METHODS: Between November 2021 and March 2022, we first formulated a preliminary infection prevention and control strategy based on the literature review and institutional experience. Then, we applied Delphi method and performed expert surveys to reach a final strategy for nursing managements during surgical operations in COVID-19 patients. RESULTS: The strategy included seven dimensions with 34 items. The positive coefficients of Delphi experts in both surveys were 100%, indicating a high coordination among experts. The degree of authority and expert coordination coefficient were 0.91 and 0.097-0.213. After the second expert survey, value assignments for importance of each dimension and item were 4.21-5.00 and 4.21-4.76 points, respectively. The coefficients of variation for dimension and item were 0.09-0.19 and 0.05-0.19, respectively. PATIENT OR PUBLIC CONTRIBUTION: Except the medical experts and research personnel, there was no other patient or public contribution involved in the study.


Assuntos
COVID-19 , Cuidados de Enfermagem , Humanos , Técnica Delphi , Correlação de Dados , Processos Grupais
14.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 5): o1357, 2012 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-22590251

RESUMO

In the crystal structure of the title compound, C(28)H(37)N(4)O(2)S(+)·Cl(-) [systematic name: 4-(1,2-benzothia-zol-3-yl)-1-({2-[(3,5-dioxo-4-aza-tricyclo-[5.2.1.0(2,6)]decan-4-yl)meth-yl]cyclo-hex-yl}meth-yl)piperazin-1-ium chloride], the anions and cations are linked by N-H⋯Cl hydrogen bonds. The crystal structure is further stabilized by C-H⋯π and C-H⋯O inter-actions.

15.
Oxid Med Cell Longev ; 2022: 1482811, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35585879

RESUMO

Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematopoietic stem cell disorders. Studies have shown the involvement of an abnormal immune system in MDS pathogenesis. The gut microbiota are known to influence host immunity and metabolism, thereby contributing to the development of hematopoietic diseases. In this study, we performed gut microbiome and plasma metabolomic analyses in patients with MDS and healthy controls. We found that patients with MDS had a different gut microbial composition compared to controls. The gut microbiota in MDS patients showed a continuous evolutionary relationship from the phylum to the species level. At the species level, the abundance of Haemophilus parainfluenzae, Streptococcus luteciae, Clostridium citroniae, and Gemmiger formicilis increased, while that of Prevotella copri decreased in MDS patients compared to controls. Moreover, abundance of bacterial genera correlated with the percentage of lymphocyte subsets in patients with MDS. Metabolomic analysis showed that the concentrations of hypoxanthine and pyroglutamic acid were increased, while that of 3a,7a-dihydroxy-5b-cholestan was decreased in MDS patients compared to controls. In conclusion, gut microbiome and plasma metabolomics are altered in patients with MDS, which may be involved in the immunopathogenesis of the disease.


Assuntos
Microbioma Gastrointestinal , Síndromes Mielodisplásicas , Bactérias , Fezes , Humanos , Metabolômica , Plasma
16.
Hematology ; 26(1): 874-880, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34753406

RESUMO

INTRODUCTION: Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases which are prone to progress into acute myeloid leukemia (AML). Iron overload (IOL) caused by transfusion occurred in most MDS patients. But how IOL influences MDS progression has not been clarified yet. METHODS: Herein, we collected clinical data from 143 MDS patients to investigate the impacts of IOL on patients survival and AML transformation. RESULTS: We found that median survival time, 3-year survival rate, leukemia-free survival (LFS) time were significantly shorter in patients with IOL than those with non-iron overload (NIOL) (P = 0.040; P = 0.044; P = 0.037). Besides, IOL was more likely to be found in higher-risk subgroups (assessed by IPSS and WPSS) of MDS patients which also promoted 2-year AML transformation. Furthermore, the serum ferritin (SF) was significantly correlated with the overall survival (OS) of MDS patients (r = -0.311, P < 0.05). The concentrations of both intracellular iron and reactive oxygen species (ROS) in CD34+ cells of bone marrow were higher in the IOL group than the NIOL group, respectively (P = 0.0426; P = 0.0185). Moreover, ROS level was closely correlated with the percentage of bone marrow blasts (r = 0.7200, P = 0.0370). Collectively, IOL threatened the survival of MDS patients and promoted AML transformation. CONCLUSION: Elevated intracellular iron and ROS in CD34+ cells of bone marrow could accelerate the abnormal proliferation of blasts.


Assuntos
Sobrecarga de Ferro/etiologia , Leucemia Mieloide Aguda/etiologia , Síndromes Mielodisplásicas/complicações , Reação Transfusional , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Transfusão de Sangue , China/epidemiologia , Feminino , Humanos , Sobrecarga de Ferro/complicações , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia , Análise de Sobrevida , Adulto Jovem
17.
Leuk Lymphoma ; 62(1): 218-223, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32985300

RESUMO

MDSCs, which are defined as a kind of negatively regulatory cells, could suppress T cell immune response in many tumor-bearing animal models and cancer patients. We supposed that MDSCs also contributed to the impaired antitumor immunity in MDS. Here we demonstrated that STAT3-ARG1 pathway could be a critical signal transduction pathway that regulated MDSCs-mediated immunosuppression. Increased MDSCs was revealed in MDS patients when compared to healthy controls. Especially, MDSCs performed higher activated STAT3 and CCR2 expression in high-risk MDS patients. The CCL2 and IL-6 levels in MDS patients were also higher than in healthy controls, which could drive recruitment and activation of MDSCs. Meanwhile, lower expression levels of CD3ζ chain, perforin and granzyme B were demonstrated in MDS patients, which were associated with downregulated activation of CD8+ T lymphocytes. The results were supported by the decreased perforin, granzyme B and IFN-γ levels in the mixed-culture system of MDSCs and CD8+ T lymphocytes in vitro. Notably, targeting STAT3 pathway by selective inhibitor could decrease ARG1 expression in MDSCs and partially reverse the lower expression levels of effector molecules on CD8+ T lymphocytes. Therefore, this study revealed the potential STAT3-ARG1 mechanism behind MDSCs and provided a promising STAT3 targeting strategy in MDS.


Assuntos
Síndromes Mielodisplásicas , Células Supressoras Mieloides , Animais , Linfócitos T CD8-Positivos , Humanos , Tolerância Imunológica , Ativação Linfocitária , Fator de Transcrição STAT3/genética
18.
Cell Rep ; 34(11): 108870, 2021 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-33730585

RESUMO

Ibrutinib, a bruton's tyrosine kinase (BTK) inhibitor, provokes robust clinical responses in aggressive mantle cell lymphoma (MCL), yet many patients relapse with lethal Ibrutinib-resistant (IR) disease. Here, using genomic, chemical proteomic, and drug screen profiling, we report that enhancer remodeling-mediated transcriptional activation and adaptive signaling changes drive the aggressive phenotypes of IR. Accordingly, IR MCL cells are vulnerable to inhibitors of the transcriptional machinery and especially so to inhibitors of cyclin-dependent kinase 9 (CDK9), the catalytic subunit of the positive transcription elongation factor b (P-TEFb) of RNA polymerase II (RNAPII). Further, CDK9 inhibition disables reprogrammed signaling circuits and prevents the emergence of IR in MCL. Finally, and importantly, we find that a robust and facile ex vivo image-based functional drug screening platform can predict clinical therapeutic responses of IR MCL and identify vulnerabilities that can be targeted to disable the evolution of IR.


Assuntos
Adenina/análogos & derivados , Resistencia a Medicamentos Antineoplásicos/genética , Linfoma de Célula do Manto/tratamento farmacológico , Linfoma de Célula do Manto/genética , Piperidinas/uso terapêutico , Transcrição Gênica , Adenina/farmacologia , Adenina/uso terapêutico , Animais , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Quinase 9 Dependente de Ciclina/antagonistas & inibidores , Quinase 9 Dependente de Ciclina/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Elementos Facilitadores Genéticos/genética , Humanos , Linfoma de Célula do Manto/enzimologia , Linfoma de Célula do Manto/patologia , Masculino , Camundongos Endogâmicos NOD , Camundongos SCID , Piperidinas/farmacologia , Proteínas Quinases/metabolismo , RNA Polimerase II/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/antagonistas & inibidores , Fatores de Transcrição/metabolismo , Transcrição Gênica/efeitos dos fármacos , Transcriptoma/genética , Resultado do Tratamento
20.
Environ Sci Pollut Res Int ; 27(16): 19970-19990, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32232750

RESUMO

This study aims to measure China's CO2 emissions embodied in fixed capital formation (FCF) from 2007 to 2017 by using both a multi-regional input-output (MRIO) model and a single-region input-output model (SRIO). Then decoupling analysis was performed for uncovering the relationship between embodied CO2 emissions and added values at provincial level. Logarithmic Mean Divisia Index (LMDI) method was further conducted to identify driving factors underlying the growth of embodied CO2 emissions. Results show that CO2 emission from FCF doubled from 2436 million tons (Mt) in 2007 to 4820 Mt in 2012, and increased slightly to 5089 Mt in 2017. Electric power, gas, and water production and supply sector (EGW) and manufacturing industry (MFI) sector were two dominant emitters from supply-side perspective, while construction (CON) was the largest demanding sector driving the embodied emissions from upstream sectors. From geographical point of view, northern provinces were the major inter-regional net exporters of embodied CO2 emissions, while eastern and southern provinces were net importers of embodied CO2 emissions. Based on such results, policy recommendations are proposed considering the relation between supply and demand sector, inter-provincial CO2 emission transfer, and local economic development to mitigate CO2 emissions from China's FCF.


Assuntos
Dióxido de Carbono/análise , Desenvolvimento Econômico , China , Indústria Manufatureira
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa