ABSTRACT
OBJECTIVE@#To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML).@*METHODS@#Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation).@*RESULTS@#The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011).@*CONCLUSION@#TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.
Subject(s)
Humans , DNA (Cytosine-5-)-Methyltransferases/genetics , DNA Methyltransferase 3A , Mutation , Leukemia, Myeloid, Acute/drug therapy , Nucleophosmin , Prognosis , fms-Like Tyrosine Kinase 3/genetics , Receptors, GABA/therapeutic useABSTRACT
Background: Benzodiazepines have a direct bronchodilatory effect. Methacholine is a non-selective muscarinic receptor agonist causing bronchoconstriction. Aim: To examine the effects of inhaled benzodiazepines, modulating bronchoconstriction induced by methacholine in patients with asthma. Patients and Methods: Twelve patients with well controlled asthma were studied. On the first day, after determining the initial values of pulmonary function, a dose response curve was carried out with progressive doses of methacholine. After the last dose, when at least a 20% drop of the initial forced expiratory volume in the first second (FEV1) was achieved, vital capacity (VC) and FEV1 were measured at 7, 15 and 30 minutes after provocation. On the second day a diazepam aerosol was inhaled by the patients prior to the same protocol with methacholine. Results: In the first day of testing, methacholine inhalation (6 mg/mL) led to a significant drop in FEV1 from 2.98 to 1.69 L. On the second day of study, in the same patients, previous inhalation with diazepam reduced the changes of FEV1 after inhalation of methacholine. This parameter decreased from 2.48 to 2.21 L. Conclusions: Inhalation of benzodiazepines reduce bronchoconstriction after a methacholine challenge in patients with asthma.
Antecedentes: Las benzodiacepinas tienen un efecto broncodilatador directo. La metacolina es un agonista muscarínico que causa bronco constricción. Objetivo: Evaluar el efecto modulador de la inhalación de diazepam sobre la bronco constricción inducida por metacolina. Pacientes y Métodos: Se estudiaron 12 pacientes con asma bien controlada. En el primer día, se determinó la curva dosis respuesta de parámetros de función pulmonar a una dosis progresiva de metacolina. Después de la última dosis, cuando se consiguió un 20% de reducción en la capacidad vital forzada en el primer segundo (FEV1), se midió FEV1 y la capacidad vital (CV) a los 7, 15 y 30 min después de la provocación. En el segundo día los pacientes se inhalaron con diazepam antes de hacer la prueba con metacolina. Resultados: En el primer día, el FEV1 bajo de 2,98 a 1,69 l con 6 mg/ml de metacolina. En el segundo día, la inhalación de diazepam redujo la respuesta a metacolina con una reducción de FEV1 de 2,48 a 2,21 L. Conclusiones: La benzodiacepinas reducen la respuesta de vasoconstricción a metacolina.