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*

OBJECTIVE: To investigate the role of acetylated modification induced by coactivator p300 in lipopolysaccharide (LPS)- induced inflammatory mediator synthesis and its molecular mechanism. METHODS: Agilent SurePrint G3 Mouse Gene Expression V2 microarray chip and Western blotting were used to screen the molecules whose expression levels in mouse macrophages (RAW246.7) were correlated with the stimulation intensity of LPS. Electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (chip-qPCR) were used to verify the binding of the molecules to the promoters of IL-6 and TNF-α genes. The effects of transfection of RAW246.7 cells with overexpression or interfering plasmids on IL-6 and TNF-α synthesis were evaluated with ELISA, and the binding level of the target molecules and acetylation level of H3K27 in the promoter region of IL-6 and TNF-α genes were analyzed by chromatin immunoprecipitation sequencing technique (chip-seq). RESULTS: Gene microarray chip data and Western blotting both confirmed a strong correlation of p300 expression with the stimulation intensity of LPS. Immunocoprecipitation confirmed the binding between p300 and c-myb. The results of EMSA demonstrated that c-myb (P < 0.05), but not p300, could directly bind to the promoter region of IL-6 and TNF-α genes; p300 could bind to the promoters only in the presence of c-myb (P < 0.05). The expressions of p65, p300 and c-myb did not show interactions. Both p300 overexpression and LPS stimulation could increase the level of promoter-binding p300 and H3K27 acetylation level, thus promoting p65 binding and inflammatory gene transcription; such effects were obviously suppressed by interference of c-myb expression (P < 0.05). Interference of p65 resulted in inhibition of p65 binding to the promoters and gene transcription (P < 0.05) without affecting p300 binding or H3K27 acetylation level. CONCLUSION LPS can stimulate the synthesis of p300, whose binding to the promoter region of inflammatory genes via c-myb facilitates the cohesion of p65 by inducing H3K27 acetylation, thus promoting the expression of the inflammatory genes.
Acetylation ; Animals ; Inflammation Mediators ; Interleukin-6/metabolism* ; Lipopolysaccharides/pharmacology* ; Mice ; Tumor Necrosis Factor-alpha/metabolism*

Aim To research the effect of PDG on bone metabolism in young rats. Methods The experimental rats were randomly divided into contro group, PDG-25 group and PDG-50 group. PDG-25 group and PDG-50 group were given PDG at the dose of 25 mg·kg

Objective To identify predictors related to condom use in different tiered female sex workers (FSWs) in Hubei Province. Methods A cross-sectional study was conducted in Hubei Province in 2015 to investigate 816 eligible FSWs by using a multistage sampling method. All data were collected by using a structured questionnaire with scales on condom use, which was designed based on the theory of planned behavior (TPB). A structural equation model (SEM) was used to identify predictors of condom use in the different tiered FSWs. Results It showed that low-tier FSWs used less condom than higher-tier FSWs in commercial sexual behaviors of the last time and during the last month(P<0.001). The TPB scores were significantly different in different tiered FSWs. The scores of PBC in low-tier FSWs were lower than those in higher-tier FSWs (11.43±2.86 vs 12.06±2.87, respectively, P=0.002); But the scores of behavioral intentions were higher than those in higher-tier FSWs (5.47±1.11 vs 5.20±1.15, respectively, P=0.001). The PBC was the major factor related to condom use in low-tier FSWs (effect coefficient=0.55, P<0.001), while the behavioral intention was the major factor related to condom use in higher-tier FSWs (effect coefficient=0.33, P<0.001). Behavioral attitude was the major factor of intention to use condoms for both low-tier (effect coefficient=0.49, P<0.001) and higher-tier FSWs (effect coefficient=0.42, P<0.001). Conclusions Changing the attitude to condom use in FSWs is an important measure to promote the behavior intention. Condom promotion interventions should focus on the perceived behavioral control in low-tier FSWs, and promote the behavior intention in higher-tier FSWs.

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*

BACKGROUNDLaparoscopic resection (LAP) for small bowel gastrointestinal stromal tumors (GISTs) is not as common as for stomach. This study aimed to evaluate the safety and efficacy of LAP for small bowel GISTs with systematic review and meta-analysis.

METHODSThe Web of Science, Cochrane Library, Embase, and PubMed databases before December 2016 were comprehensively searched to retrieve comparative trials of LAP and conventional open resection (OPEN) for GISTs of small bowel with a relevance of review object. These researches reported intraoperative and postoperative clinical course (operation time, blood loss, time to first flatus and oral intake, hospital stay, morbidity, and mortality), oncologic outcomes, and long-term survival status.

RESULTSSix studies involving 391 patients were identified. Compared to OPEN, LAP had associated with a shorter operation time (weighted mean difference [WMD] = -27.97 min, 95% confidence interval [CI]: -49.40--6.54, P < 0.01); less intraoperative blood loss (WMD = -0.72 ml; 95% CI: -1.30--0.13, P = 0.02); earlier time to flatus (WMD = -0.83 day; 95% CI: -1.44--0.22, P < 0.01); earlier time to restart oral intake (WMD = -1.95 days; 95% CI: -3.31--0.60, P < 0.01); shorter hospital stay (WMD = -3.00 days; 95% CI: -4.87--1.13, P < 0.01); and a decrease in overall complications (risk ratio = 0.56, 95% CI: 0.33-0.97, P = 0.04). In addition, the tumor recurrence and long-term survival rate showed that there was no significant difference between the two groups of patients.

CONCLUSIONSLAP for small bowel GISTs is a safe and feasible procedure with shorter operation time, less blood loss, less overall complications, and quicker recovery. Besides, tumor recurrence and the long-term survival rate are similar to open approach. Because of the limitations of this study, methodologically high-quality studies are needed for certain appraisal.

Three different forms of Linderae Radix were evaluated by HPLC combined with NIRS fingerprint. The Linderae Radix was divided into three forms, including spindle root, straight root and old root. The HPLC fingerprints were developed, and then cluster analysis was performed using the SPSS software. The near-infrared spectra of Linderae Radix was collected, and then established the discriminant analysis model. The similarity values of the spindle root and straight root all were above 0.990, while the similarity value of the old root was less than 0.850. Two forms of Linderae Radix were obviously divided into three parts by the NIRS model and Cluster analysis. The results of HPLC and FT-NIR analysis showed the quality of Linderae Radix old root was different from the spindle root and straight root. The combined use of the two methods could identify different forms of Linderae Radix quickly and accurately.

Objective To study the effects of miR?21 on the proliferation,apoptosis and MMP2 expression of HeLa cells. Methods The miR?21 or the miRNA scramble control was transfected into Hela cells. The cell proliferation was detected by the Celltiter?GloTM assay 72 h after the transfection,and the apoptosis was evaluated by the Caspase3/7 Glo? Kit. The MMP2 RNA expression was quantified by quantitative real time PCR. Results The proliferation of HeLa cells transfected with miR?21 was significantly increased compared to that of the cells transfected with miRNA scramble control. The caspase 3/7 activity in HeLa cells transfected with miR?21 was downregulated compared to that of the cells transfect?ed with miRNA negative control. The MMP2 RNA expression in HeLa cells transfected with miR?21 was increased significantly compared to the cells transfected with miRNA negative control. Conclusion miR?21 can significantly promote the proliferation of HeLa cells. In addition,it ex?hibits the anti?apoptosis effect in HeLa cells. The transfection of miR?21 significantly increased the MMP2 RNA expression,which suggests that miR?21 may promote the tumor invasion and might be a therapeutic intervention target.

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

BACKGROUNDOur previous studies have demonstrated that Tongxinluo (TXL), a traditional Chinese medicine, can protect hearts against no-reflow and reperfusion injury in a protein kinase A (PKA)-dependent manner. The present study was to investigate whether the PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis.

METHODSIn a 90-minute ischemia and 3-hour reperfusion model, minipigs were randomly assigned to sham, control, TXL (0.05 g/kg, gavaged one hour prior to ischemia), and TXL + H-89 (a PKA inhibitor, intravenously and continuously infused at 1.0 µg/kg per minute) groups. Myocardial no-reflow, necrosis, edema, and apoptosis were determined by pathological and histological studies. Myocardial activity of PKA and myeloperoxidase was measured by colorimetric method. The expression of PKA, phosphorylated cAMP response element-binding protein (p-CREB) (Ser(133)), tumor necrosis factor α (TNF-α), P-selectin, apoptotic proteins, and aquaporins was detected by Western blotting analysis.

RESULTSTXL decreased the no-reflow area by 37.4% and reduced the infarct size by 27.0% (P < 0.05). TXL pretreatment increased the PKA activity and the expression of Ser(133) p-CREB in the reflow and no-reflow myocardium (P < 0.05). TXL inhibited the ischemia-reperfusion-induced elevation of myeloperoxidase activities and the expression of TNF-α and P-selectin, reduced myocardial edema in the left ventricle and the reflow and no-reflow areas and the expression of aquaporin-4, -8, and -9, and decreased myocytes apoptosis by regulation of apoptotic protein expression in the reflow and no-reflow myocardium. However, addition of the PKA inhibitor H-89 counteracted these beneficial effects of TXL.

CONCLUSIONPKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis in the reflow and no-reflow myocardium.

Animals ; Apoptosis ; drug effects ; Aquaporin 4 ; physiology ; Cyclic AMP Response Element-Binding Protein ; physiology ; Cyclic AMP-Dependent Protein Kinases ; physiology ; Drugs, Chinese Herbal ; pharmacology ; Edema ; prevention & control ; Hemodynamics ; drug effects ; Myocardial Reperfusion Injury ; prevention & control ; Myocarditis ; prevention & control ; Swine ; Swine, Miniature