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 situ and real-time monitoring of responsive drug release is critical for the assessment of pharmacodynamics in chemotherapy. In this study, a novel pH-responsive nanosystem is proposed for real-time monitoring of drug release and chemo-phototherapy by surface-enhanced Raman spectroscopy (SERS). The Fe₃O₄@Au@Ag nanoparticles (NPs) deposited graphene oxide (GO) nanocomposites with a high SERS activity and stability are synthesized and labeled with a Raman reporter 4-mercaptophenylboronic acid (4-MPBA) to form SERS probes (GO-Fe₃O₄@Au@Ag-MPBA). Furthermore, doxorubicin (DOX) is attached to SERS probes through a pH-responsive linker boronic ester (GO-Fe₃O₄@Au@Ag-MPBA-DOX), accompanying the 4-MPBA signal change in SERS. After the entry into tumor, the breakage of boronic ester in the acidic environment gives rise to the release of DOX and the recovery of 4-MPBA SERS signal. Thus, the DOX dynamic release can be monitored by the real-time changes of 4-MPBA SERS spectra. Additionally, the strong T₂ magnetic resonance (MR) signal and NIR photothermal transduction efficiency of the nanocomposites make it available for MR imaging and photothermal therapy (PTT). Altogether, this GO-Fe₃O₄@Au@Ag-MPBA-DOX can simultaneously fulfill the synergistic combination of cancer cell targeting, pH-sensitive drug release, SERS-traceable detection and MR imaging, endowing it great potential for SERS/MR imaging-guided efficient chemo-phototherapy on cancer treatment.

[This corrects the article DOI: 10.1016/j.apsb.2022.08.024.].

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*

Several studies have shown that the tumor endothelial cells are different from the normal tissue endothelial cells. These tumor endothelial cells may contribute to tumor neo-vasculogenesis. This study was purposed to analyze the biologic features and determine the expression level of CD133 and BCR/ABL fusion gene in circulating endothelial cells (CEC) isolated from peripheral blood of CML patients, as well as to investigate the role of CEC in disease progression. Mononuclear cells were isolated from peripheral blood by density gradient centrifugation; CEC were sorted by MACS and harvested in the endothelial growth medium. The morphologic features of CEC were observed by microscopy, the cell growth rate was calculated by cell counting, and the cells were identified by immunofluorescence staining for the expression of CD31,CD34,VWF and CD133. The expression of BCR/ABL fusion gene was examined by FISH in 12 CML patients. The results indicated that the isolated CEC displayed the typical cobble-stone morphology. These cells could be identified by the positive immunofluorescence staining for CD31, CD34 and VWF, and showed more increased proliferative potential as compared to that of healthy donors. It was found that the positive rate of CD133 was 31.29% in CML patients, which was significantly different from that of healthy donors (P < 0.05). In 12 CML patients, CEC carried the same chromosome aberration as the leukemia cells (10.77%). Higher expression level of CD133 and BCR/ABL fusion gene positively correlated with progression of disease. It is concluded that the CEC may participate in invasion and angiogenesis in patients with CML and possibly correlate to the spreading and progression of the disease.
AC133 Antigen ; Adult ; Antigens, CD ; metabolism ; Cell Proliferation ; Endothelial Cells ; metabolism ; Female ; Fusion Proteins, bcr-abl ; genetics ; metabolism ; Glycoproteins ; metabolism ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; metabolism ; pathology ; Male ; Middle Aged ; Neovascularization, Pathologic ; Peptides ; metabolism ; Young Adult

OBJECTIVETo explore the therapeutic effect and safety of fire needling on rat with rheumatoid arthritis.

METHODSForty female Wistar rats were randomly divided into a normal group, a model group, a methotrexate (MTX) group and a fire needling group, 10 rats in each group. The 0.1 mL of normal saline was subcutaneously injected in rat's right back paw in the normal group, while the other groups received subcutaneous injection of 0.1 mL of complete Freund's adjuvant to establish the model. The pricking method was applied in the fire needling group at "Jiaji" (EX-B 2), "Zusanli" (ST 36) and Ashi points with a depth of 5 mm, once every three days, and totally eight times were required. In the MTX group, with intragastric administration of 2.0 mg/kg per rat, the treatment was given once every seven days, and totally four times were required. The weight, swelling rate of foot, joint pain score and polyarthritis index of rats in each group as well as the pathological change of liver tissue under light microscope were observed.

RESULTSThe weight, swelling rate of foot, joint pain score and polyarthritis index in the model group were significantly higher than those in the normal group (P < 0.05, P < 0.01), after the treatment, the above-mentioned indexes in the two treatment groups were obviouly dereased as componed with those in the model group (all P < 0.01), and there were statistical differences between the fire needling group and MTX group (P < 0.05, P < 0.01). Compared with the normal group, inflammatory cells were appeared with a cluster distribution in the liver cells of rats in the model group. The inflammatory cells were reduced in the MTX group and fire needling group, and liver cells had degenerative edema and cell nucleus were largen and deformed in the MTX group.

CONCLUSIONThe fire needling has significant efficacy for rats with adjuvant arthritis (AA) without any damage to the liver, which coud have a better control of disease progression of rheumatoid arthritis .

Acupuncture Therapy ; adverse effects ; instrumentation ; methods ; Animals ; Arthritis, Rheumatoid ; therapy ; Female ; Humans ; Rats ; Rats, Wistar

This study was purposed to explore the correlation of CXCR4, CCR1, CCR2 expression with curative effect of multiple myeloma (MM). Flow cytometry was used to detect the expressions of CXCR4, CCR1, CCR2 on cell surface of bone marrow from 48 newly diagnosed MM patients. These patients were divided into two groups: one group with expression of chemokine receptor (group I) and another group without expression of chemokine receptor (group II). The group I was consisted of 34 patients, but 3 out of them could not be continuously followed up. The group II was consisted of 14 patients. The MM patients of 2 groups were treated with chemotherapeutic drugs for 3 and 6 months, the curative efficacy of 2 groups were compared. The results showed that after treating for 3 and 6 months the effective rates of group I and group II were 80.6% (25/31) vs 50% (7/14) and 83.9% (26/31) vs 50% (7/14) respectively, which suggested that curative efficacy of group I was better than that of group II (p < 0.05). It is concluded that CXCR4, CCR1, CCR2 may be used as indexes for evaluating curative effect of MM patients.
Adult ; Aged ; Aged, 80 and over ; Female ; Flow Cytometry ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; drug therapy ; metabolism ; Receptors, CCR1 ; metabolism ; Receptors, CCR2 ; metabolism ; Receptors, CXCR4 ; metabolism ; Treatment Outcome

Objective To observe the coronary vessel lumen diameter and bifurcation angle in subjects with normal CT coronary angiography (CTCA) imaging.Methods64-row CT coronary angiography imaging from 526 adult people with excellent image quality and normal vascular image were analyzed in this study.The lumen diameter from the origin to distal with 2 mm lumen of left main coronary artery (LM),anterior descending branch (LAD),left circumflex branch (LCX) and right coronary artery (RCA) was measured at 1 cm interval in CPR image.The vascular tapered ratio was calculated.The bifurcation angle in the diagonal branch,obtuse marginal branch,posterior descending branch,acute marginal branch as well as the origin diameter was also measured in VR image.Results The LAD average length was 13 cm and lumen diameter was 3.92 mm at origin and 2.10 mm at distal.The average decremented ratio of LAD was 7.7％ ( male 7.0％,female 8.4％ ).The maximal decremented ratio 8.0％ -10.0％ occurred at 3 -5 cm apart from the origin of LAD.The LCX average length was 13 cm and lumen diameter was 3.57 mm at origin and 2.10 mm at distal.The average decremented ratio of LCX was 9.7％( male 9.6％,female 9.7％ ).Lumen decremented ratio was less than 3.0％ between origin and proximal 3 cm and 8.3％ - 10.7％ in the rest portion of the LCX.The RCA average length was 18 cm and lumen diameter was 3.97 mm at origin and 2.15 mm at distal.The average decremented ratio of RCA was 5.1％(male 4.9％,female 5.3％ ).The decremented ratio of RCR was less than 4.0％ between origin and proximal 10 cm and 6.1％ - 15.2％ in the rest portion.The bifurcation angle was 50,55,66 and 76 degree for LAD with diagonal branch,LCX with obtuse marginal branch,RCA with posterior descending branch and RCA with obtuse marginal branch respectively.Conclusion Coronary artery length,lumen diameter and decremented ratio as well as bifurcation angel could be identified in 64 row CTCA image in vivo.This information could help us to understand the in vivo coronary artery anatomy.

Objective Development of new methods, ELISA and immunostrip test, for the diagnosis of nasopharyngeal carcinoma. Methods The engineering purified antigens coat plate or absorb on nitrocellulose filter. The plate and diagnostic strips carrying antigens were used for detection of IgG antibody in the sera from nasopharyngeal carcinoma patients and outpatients patients. Results 127 cases sera from nasopharyngeal carcinoma patients were parallel detected TK/ IgG antibody by ELISA and immunostrips. The TK/IgG antibody are all positive in the 127 cases of nasopharyngeal carcinoma patients. 55 cases show positive by ELISA, 58 cases positive by immunostrips in 247 cases sera from outpatient. The antibody positive rate to early antigen p54 lower then to TK. Conclusion ELISA and imuunostrips are sensitive and specific means for detection of the IgG antibody to TK of EBV and the diagnosis of nasopharyngeal carcinoma.

OBJECTIVETo investigate the effectiveness and advantages of the Carto merge technique in guiding radiofrequency catheter ablation (RFCA) of permanent atrial fibrillation (AF).

METHODSA total of 15 patients with permanent AF underwent RFCA under guidance of the Carto merge technique. The virtual electroanatomical map of the left atrium (LA) and pulmonary veins (PVs) were reconstructed with Carto system during the procedure. Then the electroanatomical map was integrated with 3-D images of cardiac magnetic resonance angiography to form Carto merge map. Circumferential pulmonary vein ablation was performed first until complete PVs electric isolation confirmed by lasso catheter. If AF was not terminated, lesion lines on roof of LA, mitral isthmus, and tricuspid isthmus were produced. Finally direct current (DC) cardioversion were given if sinus rhythm did not return.

RESULTSAF were terminated spontaneously during RFCA in 2 patients, and by DC cardioversion in the remaining 13 patients. Persistent AF recurred on 24 hours, first week, and 5th week, respectively in three patients. The remaining 12 patients were all free of AF during follow-up (1-10 months). The success rate was 80% in the study.

CONCLUSIONSCarto merge technique can effectively guide RFCA of permanent AF. When combined with single Lasso mapping, it can simplify the mapping and enhance the success rate of RFCA of permanent AF.

Atrial Fibrillation ; surgery ; Catheter Ablation ; methods ; Humans