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.
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 use*

In this study, we investigated the anti-osteoporotic activity and mechanism of action of extract of Panax quiquefolium L. based on zebrafish model combined with metabolomics technology. A zebrafish model of prednisolone-induced osteoporosis was used to compare the anti-osteoporotic activity of Panax quiquefolium L., and the expression of osteoblast-associated genes and osteoclast-associated genes in zebrafish was detected by quantitative real-time PCR (qRT-PCR), using bone fluorescence area and fluorescence density as evaluation indexes. Metabolomics based on ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) was used to explore the change patterns of biomarkers and the metabolic pathways affected. The results showed that the 50% ethanol extracts of Panax quiquefolium L. from Jilin, Canada, Wenden and the United States can significantly improve the bone fluorescence area of zebrafish compared with model group. Furthermore, four sources 50% ethanol extracts of Panax quiquefolium L. except United States also can significantly improve the bone fluorescence density of zebrafish. In addition, PCR showed that extract of Panax quiquefolium L. can significantly up-regulated the expression of vitamin D receptor b (vdrb), collagen type I α2 (col1a2) and cysteine-rich acidic secreted protein (sparc) genes, and down-regulated the expression of matrix metalloproteinase 9 (mmp9), anti-tartrase acid phosphatase (trap) and cathepsin K (ctsk) genes. Metabolomic analysis identified 24 key differential metabolites. Furthermore, pathway analysis showed that Panax quiquefolium L. could regulate the levels of 10 key biomarkers by participating in purine metabolism, tricarboxylic acid cycle and pentose phosphate metabolism and improve the osteoporosis status of zebrafish. This study preliminically revealed the anti-osteoporosis mechanism of 50% ethanol extract from Panax quiquefolium L. through multi-component, multi-target and multi-pathway and also provides theoretical basis for clinical development and utilization of anti-osteoporosis products of Panax quiquefolium L. This experiment was approved by the Experimental Animal Welfare Ethics Committee of the Institute of Biology, Shandong Academy of Sciences (approval number: SWS20181002).

OBJECTIVE: To investigate effects of berberine (BBR) on cholesterol synthesis in HepG2 cells with free fatty acid (FFA)-induced steatosis and to explore the underlying mechanisms. METHODS: A steatosis cell model was induced in HepG2 cell line fed with FFA (0.5 mmol/L, oleic acid:palmitic acid = 2:1), and then treated with three concentrations of BBR; cell viability was assessed with cell counting kit-8 assays. Lipid accumulation in cells was observed through oil red O staining and total cholesterol (TC) content was detected by TC assay. The effects of BBR on cholesterol synthesis mediators were assessed by Western blotting and quantitative polymerase chain reaction. In addition, both silent information regulator 1 (SIRT1) and forkhead box transcription factor O1 (FoxO1) inhibitors were employed for validation. RESULTS: FFA-induced steatosis was successfully established in HepG2 cells. Lipid accumulation and TC content in BBR groups were significantly lower (P < 0.05, P < 0.01), associated with significantly higher mRNA and protein levels of SIRT1(P < 0.05, P < 0.01), significantly lower sterol regulatory element-binding protein 2 (SREBP2) and 3-hydroxy 3-methylglutaryl-CoA reductase levels (P < 0.05, P < 0.01), as well as higher Acetyl-FoxO1 protein level (P < 0.05, P < 0.01) compared to the FFA only group. Both SIRT1 inhibitor SIRT1-IN-1 and FoxO1 inhibitor AS1842856 blocked the BBR-mediated therapeutic effects. Immunofluorescence showed that the increased SIRT1 expression increased FoxO1 deacetylation, and promoted its nuclear translocation. CONCLUSION BBR can mitigate FFA-induced steatosis in HepG2 cells by activating SIRT1-FoxO1-SREBP2 signal pathway. BBR may emerge as a potential drug candidate for treating nonalcoholic hepatic steatosis.
Berberine/pharmacology* ; Cholesterol ; Forkhead Box Protein O1/genetics* ; Humans ; Non-alcoholic Fatty Liver Disease/drug therapy* ; Sirtuin 1/genetics* ; Sterol Regulatory Element Binding Proteins

Objective: To investigate the impact of FLT3-ITD and DNMT3A R882 double mutations to the prognosis of acute myeloid leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods: FLT3-ITD, DNMT3A, C-kit, CEBPA, FLT3-TKD and NPM1 mutations were detected in 206 newly diagnosed AML patients by Sanger sequencing (M(3) and those received FLT3 inhibitor were excluded). Clinical data of AML patients were retrospectively analyzed to compare the prognosis of each gene mutation group. Results: ①Of 206 patients, 104 were male and 102 female with a median age of 38 (3-63) years, including 6 cases of M(0), 24 cases of M(1), 56 cases of M(2), 39 cases of M(4), 63 cases of M(5), 6 cases of M(6) and 12 unclassified cases. ②All 206 patients were divided into four groups according to the mutation gene at the time of diagnosis: FLT3-ITD(+) DNMT3A R882(+) group (group A), FLT3-ITD(+) DNMT3A R882(-) group (group B), FLT3-ITD(-) DNMT3A R882(+) group (group C) and FLT3-ITD(-) DNMT3A R882(-) groups (group D). Gender, leukocyte count at diagnosis, chromosome karyotype, the median age, FAB classification, disease status prior to transplantation, type of donor, conditioning regimen and GVHD were not significantly different between four groups (P>0.05). ③The 2-year cumulative recurrence rate (CIR) of group A was significantly higher than that of other groups [group A (72.2±2.6)%, group B (38.6±0.6)%, group C (36.8±1.6)%, group D (27.8±0.1)%, respectively, P<0.05], while the 2-year overall survival (OS) rate and 2-year leukocyte-free survival (LFS) rate were lower than those of other groups [group A (30.9±13.3)%, (11.3±10.2)%; group B (67.5±7.8)%, (47.9±8.4)%; group C (61.4±12.4)%, (56.8±12.5)%; group D (80.1±3.7)%, (79.7±3.6)%, respectively, P<0.05]. Conclusion: AML patients with FLT3-ITD and DNMT3A R882 double mutations had a very high CIR and low OS, LFS after transplantation.
Adolescent ; Adult ; Child ; Child, Preschool ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; DNA Methyltransferase 3A ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia, Myeloid, Acute ; Male ; Middle Aged ; Mutation ; Nucleophosmin ; Prognosis ; Retrospective Studies ; Young Adult ; fms-Like Tyrosine Kinase 3/genetics*

OBJECTIVETo determine evaluate the effect of health-promoting lifestyle on the outcomes of suboptimal health status (SHS).

METHODSA prospective population cohort was conducted by consecutively enrolling 5676 college students who took routine health examination from March to May 2013. The participants were assessed for baseline health status and lifestyle and 2972 participants with SHS were followed up for 1.5 years. Exposure was defined as an unhealthy lifestyle. The health-promoting lifestyle was assessed via the Health-promoting Lifestyle Profile (HPLP-II). SHS was evaluated using the medical examination report and Sub-health Measurement Scale V1.0 (SHMS V1.0).

RESULTSAmong the 2972 students with SHS, 422 showed recovery of the healthy status at 1.5 year follow-up, 579 showed progression into disease conditions, and 1971 remained in SHS. The participants with recovered health status presented with significant increase of SHMS V1.0 scores by 8.75∓6.95 points compared to the baseline assessment (t=-2.14, P=0.000) in physiological, psychological and social dimensions; they also showed a marked improvement of HPLP-II scores by 14.73 points in 6 dimensions (t=-15.34, P=0.000). Multivariable regression analyses with adjusted demographic variables revealed a significant association between health status and health-promoting lifestyle (P<0.05). Compared with a healthy lifestyle (minimal exposure), a 'poor' lifestyle (the highest level of exposure) was associated with a 30 times higher risk of developing SHS (OR: 30.598, 95% CI: 3.928-238.331), while a 'moderate' lifestyle (a relatively high-level exposure) had a 24 times higher risk of SHS (OR: 23.988, 95%CI: 14.695-39.158), and a suboptimal lifestyle had a nearly 4 times higher risk of SHS (OR: 4.306, 95%CI: 2.767-6.702).

CONCLUSIONs SHS may evolve into either a healthy or a disease condition. A unhealthy lifestyle is the important risk factor contributing to the progression of SHS into a disease condition, suggesting the importance of intervention of unhealthy lifestyles in promoting good health.

Health Behavior ; Health Status ; Healthy Lifestyle ; Humans ; Prospective Studies ; Regression Analysis ; Risk Factors ; Students

OBJECTIVETo investigate associations between health-promoting lifestyle and suboptimal health status (SHS) in the population of Guangdong province.

METHODSA cross-sectional survey was conducted in a clustered sample of 24 159 individuals aged 12-80 years from 2012 to 2013. Health-promoting lifestyle was assessed via the Health-Promoting Lifestyle Profile (HPLP-II), and SHS was evaluated using the medical examination report and Sub-health Measurement Scale V1.0 (SHMS V1.0).

RESULTSOf the 24159 participants, subjects with SHS (46.0%) and disease status (35.2%) accounted for a much higher percentage than healthy subjects (18.8%). Regression analyses revealed a significant association between health status and healthy lifestyle (P<0.001). Unhealthy lifestyle was an important risk factor for SHS and disease, especially the former. Compared with the participants with a healthy lifestyle (minimal exposure), after demographic adjustment, subjects with a 'poor' lifestyle (maximal exposure) were at a 43 times higher risk of developing SHS (OR: 42.825, 95% CI: 30.567-59.997), those with a general lifestyle were at a 21 times higher risk of SHS (OR: 21.072, 95%CI: 17.258-25.729), and those with a suboptimal lifestyle had a 4 times higher risk (OR: 4.085, 95%CI: 3.352-4.979). In the general population, the major risk factors for SHS included poor stress management, poor self-actualization, inactive exercise and poor interpersonal relationship.

CONCLUSIONs Unhealthy lifestyles are significantly related to an increased risk of SHS. Intervention of unhealthy lifestyles, controlling the risk factors of SHS, and rigorous management of the time window of SHS are necessary to promote the heath status.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Cross-Sectional Studies ; Health Promotion ; Health Status ; Humans ; Life Style ; Middle Aged ; Regression Analysis ; Risk Factors ; Young Adult

The aim of this study was to investigate the effects of H3K27 methylation inhibitor EPZ005687 on the apoptosis, proliferation and cell cycle of U937 cells and normal CD34⁺ cells. The U937 cells and normal CD34⁺ cells were treated with different concentration of EPZ005687 at different time points. The apoptosis rate was determined by Annexin V/PI staining. The cell proliferation and cell cycle was determined using WST-1 assay and 7-AAD assay, respectively. The activity of H3K27 methylation was detected by chemiluminescent immunoassay. The results showed that the EPZ005687 induced an obvious apoptosis of U937 cells. The apoptotic rate was 3.96% ± 0.79%,5.74% ± 0.73%,13.34% ± 1.77% and 25.24% ± 2.55% in U937 cells treated with 0.5, 1, 5 and 10 µmol/L EPZ005687 for 48 hours, respectively. However, EPZ005687 had rare effect on normal bone marrow(NBM) CD34⁺ cells. The apoptotic rate was 3.64% ± 0.62%,4.28% ± 0.99%,6.18% ± 1.19% and 7.56% ± 1.34% after U937 cells were treated with 0.5, 1, 5 and 10 µmol/L EPZ005687 for 48 hours, respectively. EPZ005687 inhibited obviously the proliferation of U937 cells but had weak effect on the proliferation of NBMCD34⁺ cells. The inhibitory effect of EPZ005687 on U937 cells was time-dependent after treated with 0.5, 1, 5 and 10 µmol/L EPZ005687 from 12 to 96 hours. EPZ005687 induced G1 phase blocking (G1%, 64.18% ± 13.27% vs 49.43% ± 12.54%) and decreased the percentage of cells in S phase (9.67% ± 2.61% vs15.26% ± 5.58%) in U937 cells. However, EPZ005687 had no effect on the cell cycle of NBMCD34⁺ cells. In addition, EPZ005687 produced obviously depletion of H3K27 methylation in U937 cells (P < 0.05), but hardly had effect on the H3K27 methylation of NBMCD34⁺ cells. It is concluded that the EPZ005687 inhibites proliferation, induces apoptosis and cell cycle blocking in G1 phase in leukemia cells. This agent may have potential value in clinical application.
Antigens, CD34 ; metabolism ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Humans ; Indazoles ; pharmacology ; Methylation ; Pyridones ; pharmacology ; U937 Cells

OBJECTIVETo study the frequency of a 9 bp deletion polymorphism of mitochondrial DNA (mtDNA) in ethnic Miao, Buyi and Dong populations from Guizhou province.

METHODSPolymerase chain reaction-polyacrylamide gel electrophoresis (PCR-PAGE) was used to detect the 9 bp deletion. The result was verified with DNA sequencing.

RESULTSTwo polymorphisms, including a standard pattern and a short pattern (the 9 bp deletion), were found among the three ethnic groups. The frequency of short pattern in 304 males was 23.0%. Respectively, those of Miao, Buyi and Dong ethnics were 28.6%, 26.8% and 13.7%. A statistically significant difference was detected among the three groups (P<0.05).

CONCLUSIONThe frequencies of the 9 bp polymorphism were relatively high among ethnic Miao, Buyi and Dong populations from Guizhou, and there was a significant difference between the three.

Base Sequence ; China ; ethnology ; DNA, Mitochondrial ; genetics ; Gene Deletion ; Humans ; Male ; Molecular Sequence Data ; Polymerase Chain Reaction ; Polymorphism, Genetic ; Sequence Analysis, DNA

OBJECTIVETo investigate allelic frequencies of interluekin-10 (IL-10) gene promoter in Miao, Dong and Buyi ethnics of Guizhou.

METHODSTaqMan MGB-based real-time PCR was used to determine the genotypes of IL-10 -819 and IL-10 -592 in 589 Miao, Dong and Buyi ethnics of Guizhou.

RESULTSThe allelic frequency of IL-10 -819 in Miao ethnics was significantly different from those in Dong or Buyi ethnics. Allelic frequencies of IL-10 -592 in Miao ethnics was significantly different from those in Dong or Buyi ethnics. In Miao, Dong and Buyi ethnics, the distributions of genotype frequencies of IL-10 -819 and IL-10 -592 were statistically different from Han ethnics from Guizhou and Taiwan of China as well as South Koreans.

CONCLUSIONThere is a heterogeneity in the frequencies of polymorphisms of IL-10 promoter among different ethnic groups.

Alleles ; Asian Continental Ancestry Group ; ethnology ; genetics ; China ; ethnology ; Gene Frequency ; Genetics, Population ; Genotype ; Humans ; Interleukin-10 ; genetics ; Polymorphism, Single Nucleotide ; Population Groups ; genetics ; Promoter Regions, Genetic

OBJECTIVETo study the clinical outcome, adverse effect and treatment cost of homoharringtonine (HHT) in combination with all-trans retinoic acid (ATRA) and arsenic trioxide (AS2O3) for newly diagnosed with patients acute promyelocytic leukemia (APL).

METHODSClinical data of treatment of newly diagnosed patients with APL in experimental group (HHT + ATRA + AS2O3, n = 14) and control group \[Idarubicin (IDA) + ATRA + AS2O3, n = 21\] were analyzed retrospectively. The therapeutic effects, side effects and costs during induction therapy were compared between the two groups.

RESULTS(1) The complete remission (CR) rate were 92.9% (13/14) and 95.2% (20/21) in experimental group and control group, respectively. The time to achieve CR were (28.1 ± 3.8) and (31.7 ± 4.2) days, respectively (P > 0.05). The negative rate of PML-RARα fusion gene at the time of CR were 76.9% (10/13) and 75.0% (15/20), respectively, and that in CR patient at the end of the first cycle treatment were 100.0% (13/13) and 95.0% (19/20), respectively (P > 0.05). (2) 5-year overall survival (OS) rate were (92.6 ± 0.6)% and (89.9 ± 0.5)%, respectively (P > 0.05), 5-year disease free survival (DFS) rate were 100.0% and (86.8 ± 0.6)%, respectively (P > 0.05). (3) During induction therapy, the incidence of infection in experimental and control group were 23.1% (3/13), 60.0% (12/20), respectively (P < 0.05). The amount of platelet transfusion were (54.7 ± 29.6) and (76.5 ± 25.6) units, respectively (P > 0.05), and that of fresh frozen plasma were (1157.1 ± 238.4) and (1423.5 ± 324.6) ml, respectively (P > 0.05). The total medical costs (excluding HHT and IDA) in experimental and control group were (36074.9 ± 1245.6) and (50564.5 ± 3658.4)CNY, respectively (P < 0.05).

CONCLUSIONHHT in combination with ATRA and AS2O3 regimen for newly diagnosed APL has a better efficacy, a higher long-term survival rate, and a lower costs, which is one of the reasonable choice.

Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Arsenicals ; therapeutic use ; Female ; Harringtonines ; therapeutic use ; Humans ; Leukemia, Promyelocytic, Acute ; drug therapy ; Male ; Middle Aged ; Oxides ; therapeutic use ; Retrospective Studies ; Treatment Outcome ; Tretinoin ; therapeutic use