Efficacy of Venetoclax Plus Azacitidine in Relapsed/Refractory Acute Myeloid Leukemia Patients with FLT3-ITD Mutation / 中国实验血液学杂志

OBJECTIVE@#To explore the efficacy of venetoclax (VEN) plus azacitidine (AZA) in patients with FLT3-ITD mutated relapsed/refractory acute myeloid leukemia (FLT3-ITDmut R/R AML) and analyze the molecular genetic characteristics of the patients.@*METHODS@#Clinical baseline characteristics and follow-up data of 16 R/R AML patients treatd with VEN plus AZA in the hematology department of Shenzhen Second People's Hospital from November 2018 to April 2021 were collected. Leukemia related genes were detected by next-generation sequencing(NGS) or PCR. The relationship between the efficacy of VEN plus AZA and molecular genetics characteristics of patients with FLT3-ITDmut R/R AML were analyzed.@*RESULTS@#14.3% (1/7) of the patients in FLT3-ITDmut group and 22.2% (2/9) of the patients in FLT3-ITDwt group achieved complete remission (CR)/CR with incomplete blood count recovery (CRi), respectively, with no significant difference (P=0.69). There was no significant difference in overall response rate (ORR) (CR/CRi+PR) between FLT3-ITDmut group and FLT3-ITDwt group [42.9%(3/7) vs 44.4%(4/9), P=0.95], too. The median overall survival (OS) time of FLT3-ITDmut patients was significantly shorter than that of FLT3-ITDwt patients (130 vs 300 days, respectively) (P =0.02). Co-existing mutations of FLT3-ITD and IDH1 were detected in one patient who achieved CR. Co-existing mutations of FLT3-ITD and SF3B1 were found in one patient who achieved PR. Three FLT3-ITDmut R/R AML patients accompanied with NPM1 mutation had no response to VEN plus AZA.@*CONCLUSION@#VEN plus AZA showed a certain effect on patients with FLT3-ITDmut R/R AML. To improve OS of the patients, bridging transplantation is need. IDH1 and SF3B1 mutations might predict that patients with FLT3-ITDmut R/R AML have treatment response to VEN plus AZA, while the combination of NPM1 mutation may indicate poor response.

Effective components of Shengxian Decoction and its mechanism of action in treating chronic heart failure based on UHPLC-Q-TOF-MS integrated with network pharmacology / 中国中药杂志

This study aimed to elucidate the effective components of Shengxian Decoction and its mechanism of action in treating chronic heart failure. Firstly, UHPLC-Q-TOF-MS was established to identify the main chemical constituents in the rat serum after intragastric administration with Shengxian Decoction. Secondly, the absorbed components in serum were then used for the network pharmacology analysis to infer the mechanism and effective components. Targets for constituents in serum were predicted at TCMSP and Swiss-TargetPrediction database. An association network map was drawn by network visualization software Cytoscape 3.6.1. Finally, GO enrichment analysis and KEGG pathway enrichment analysis were carried out for the core target genes. By UHPLC-Q-TOF-MS, 18 prototype compounds were definitely identified, including five compounds from Astragali Radix, four compounds from Anemarrhenae Rhizoma, four compounds from Bupleuri Radix, four compounds from Cimicifugae Rhizoma, and one compound from Platycodonis Radix. Those components of Shengxian Decoction were closely associated with 13 key protein targets, including inflammatory factors, like IL6, IL1 B, TNF, PTGS2, IL10; redox enzymes CAT, HMOX1, and MPO; cardiovascular targets, like VEGFA, NOS3, and NOS2; and transmememial proteins CAV1 and INS. Network pharmacology analysis showed that the 18 compounds could be responsible for the treatment of chronic heart failure by regulating HIF-1 signaling pathways, PI3 K-Akt signaling pathways, cGMP-PKG signaling pathways, cAMP signaling pathways and TNF signaling pathways. This study provided a scientific basis for mechanism and effective ingredients of Shengxian Decoction.

Value of dynamic contrast-enhanced CT combined with MRI in differential diagnosis of adrenal adenoma and metastatic tumor / 中国医师杂志

Objective@#To investigate the clinical significance of dynamic contrast-enhanced computed tomography (CT) combined with magnetic resonance imaging (MRI) in differential diagnosis of adrenal adenoma and metastasis.@*Methods@#120 patients with adrenal adenoma who were examined by enhanced MRI and enhanced CT before operation were collected. According to the pathological examination after operation, they were divided into adrenal adenoma group (86 cases) and adrenal metastasis group (34 cases). The difference of time-density curve between the two groups was compared, and the diagnostic criteria were evaluated by using receiver operating characteristic (ROC) curve.@*Results@#Dynamic CT and dynamic MRI were mainly type A, followed by type C, B, D and E. Dynamic CT and dynamic MRI were mainly type B, followed by type D/E, type A and type C. There were significant differences in type A, B, C, E dynamic CT and dynamic MRI between the two groups (P<0.05); there was no significant difference in type D dynamic CT and dynamic MRI between the two groups (P>0.05). The AZ value of adrenal adenomas ranged from 0.714 to 0.825 and that of adrenal metastasis ranged from 0.872 to 0.965 at 3-30 minutes delay.@*Conclusions@#Dynamic contrast-enhanced CT combined with MRI in patients with adrenal adenoma and metastasis has a time-density difference, 5min has high discriminant value in time lapse.

Value of dynamic contrast-enhanced CT combined with MRI in differential diagnosis of adrenal adenoma and metastatic tumor / 中国医师杂志

Objective To investigate the clinical significance of dynamic contrast-enhanced computed tomography (CT) combined with magnetic resonance imaging (MRI) in differential diagnosis of adrenal adenoma and metastasis.Methods 120 patients with adrenal adenoma who were examined by enhanced MRI and enhanced CT before operation were collected.According to the pathological examination after operation,they were divided into adrenal adenoma group (86 cases) and adrenal metastasis group (34 cases).The difference of time-density curve between the two groups was compared,and the diagnostic criteria were evaluated by using receiver operating characteristic (ROC) curve.Results Dynamic CT and dynamic MRI were mainly type A,followed by type C,B,D and E.Dynamic CT and dynamic MRI were mainly type B,followed by type D/E,type A and type C.There were significant differences in type A,B,C,E dynamic CT and dynamic MRI between the two groups (P ＜ 0.05);there was no significant difference in type D dynamic CT and dynamic MRI between the two groups (P ＞ 0.05).The AZ value of adrenal adenomas ranged from 0.714 to 0.825 and that of adrenal metastasis ranged from 0.872 to 0.965 at 3-30 minutes delay.Conclusions Dynamic contrast-enhanced CT combined with MRI in patients with adrenal adenoma and metastasis has a time-density difference,5min has high discriminant value in time lapse.

Synergistic killing effect of arsenic trioxide combined with curcumin on KG1a cells / 中国实验血液学杂志

This study was aimed to explore the effect of arsenic trioxide combined with curcumin on proliferation and apoptosis of KG1a cells and its potential mechanism. The cell survival rate was mesured by MTT; colony formation capacity was examined by methylcellulose colony formation test; flow cytometry was used to analyse the cell surface molecules, cell apoptosis rate and cell cycle; the cell morphology was observed with Wright-Giemsa staining and the protein expression of BCL-2, BAX, PARP was detected by Western blot. The results showed that the phenotype of KG1a cells was CD34(+)CD38(-), while the phenotype of HL-60 cell was CD34(+)CD38(+). The former possessed a stronger colony ability than the latter. Effect of curcumin and arsenic trioxide alone on cell proliferation and inhibition was in dose-dependent manner. Compared with single drug-treatment group, the cell survival rate and colony number were lower, and the apoptosis rate was higher in combined drug-treatment group. Protein expression of BCL-2 and PARP was upregulated, while the protein expression of PARP was downregulated in the combined treatment group. It is concluded that compared with HL-60 cells, KG1a cells are the earlier leukemia stem/progenitor cells. Arsenic trioxide combined with curcumin can effectively inhibit the KG1a cell proliferation and induce apoptosis, which may be associated with the downregulation of BCL-2 and PARP protein expression and the upregulation of BAX protein expression.

Effect of honokiol on proliferation and apoptosis in HL-60 cells and its potential mechanism / 中国实验血液学杂志

This study was aimed to investigate the effect of Honokiol (HNK) on proliferation and apoptosis of acute myeloid leukemia HL-60 cells and its potential mechanism. Inhibitory effect of HNK on the HL-60 cell proliferation was detected by MTT assay. Flow cytometry was used to detect the change of cell cycle and AnnexinV/PI staining was used to detect apoptosis. Western blot was applied to analyze the cell cycle protein (cyclins), cyclin-dependent kinase (CDK), P53, P21, P27, BCL-2, BCL-XL, Bax, caspase-3/9 and proteins for MAPK signal pathway. The results showed that HNK could inhibit the proliferation of HL-60 cells in time- and dose dependent ways. HNK arrested HL-60 cells in G0/G1 phase, and S phase cells decreased significantly (P < 0.05). The expression of cyclin D1, cyclin A, cyclin E and CDK2/4/6 were significantly down-regulated (P < 0.05), the expression of P53 and P21 was significantly upregulated after treating for 24 h with HNK (P < 0.05). After 24 h treatment with HNK, HL-60 cell apoptosis increased significantly with the upregulation of activated caspase-3, -9, BAX expression and the downregulation of BCL-2, BCL-XL expression. The MAPK subfamily, P38 and JNK were not significantly changed, but the expression of MEK1/2-ERK1/2 was significantly downregulated (P < 0.05). It is concluded that HNK arrestes the cells at G0/G1 phase and induces HL-60 cell apoptosis through the intervention of MEK1/2-ERK1/2 signaling pathway.

Association of alpha fetoprotein in hepatocellular carcinoma with activation of hepatic progenitor cells and patient prognosis / 第二军医大学学报

Objective: To investigate the relationship of alpha fetoprotein (AFP) with activation of hepatic progenitor cells in hepatocellular carcinoma (HCC) and the prognosis of HCC patients. Methods: The clinical data of 92 HCC patients who received curative hepatectomy were retrospectively analyzed. The patients included 76 males and 16 females, with a median age of 51 (ranging 25-72) years. Expression of AFP and CK19 protein was immunohistochemically stained and quantified. Kaplan-Meier survival analysis was used to observe the influence of AFP expression on postoperative survival of patients. Cochran-armitage trend test was used to analyse the association of AFP expression with activation of progenitor cells (CK19 staining). Results: Patientswith high AFP expression had a significantly shorter survival than thosewith low AFP expression (P=0. 021). The activation score of hepatic progenitor cells was positively correlated with serum AFP concentration (P = 046) and AFP expression in tumor tissues (P<0. 001). Conclusion: AFP expression in HCC tissue predicts a poor prognosis. AFP is closely associated with activation of hepatic progenitor cells.