Fusion Proteins, bcr-abl ; genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; complications ; genetics ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; etiology

In this study, we explored the feasibility of biotin-mediated modified polymeric micelles for pancreatic cancer targeted photodynamic therapy. Poly (ethylene glycol)-distearoyl phosphatidyl ethanolamine (mPEG2000-DSPE) served as the drug-loaded material, biotin-poly(ethylene glycol)-distearoyl phosphatidyl ethanolamine (Biotin-PEG3400-DSPE) as the functional material and the polymeric micelles were prepared by a thin-film hydration method. The targeting capability of micelles was investigated by cell uptake assay in vitro and fluorescence imaging in vivo and the amounts of Biotin-PEG-DSPE were optimized accordingly. Hypocrellin B (HB), a novel photosensitizer was then encapsulated in biotinylated polymeric micelles and the anti-tumor efficacy was evaluated systemically in vitro and in vivo. The results showed that micelles with 5 mol % Biotin-PEG-DSPE demonstrated the best targeting capability than those with 20 mol % or 0.5 mol % of corresponding materials. This formulation has a small particle size [mean diameter of (36.74 ± 2.16) nm] with a homogeneous distribution and high encapsulation efficiency (80.06 ± 0.19) %. The following pharmacodynamics assays showed that the biotinylated micelles significantly enhanced the cytotoxicity of HB against tumor cells in vitro and inhibited tumor growth in vivo, suggesting a promising potential of this formulation for treatment of pancreatic cancer, especially those poorly permeable, or insensitive to radiotherapy and chemotherapy.
Animals ; Antineoplastic Agents ; chemistry ; Biotin ; Drug Carriers ; chemistry ; Drug Screening Assays, Antitumor ; Humans ; Micelles ; Pancreatic Neoplasms ; drug therapy ; Photochemotherapy

BACKGROUND:Our previous studies confirmed that NGF-PEG-PLGA-NPs has good sustained release effect and biological activity in vitro, and can induce the differentiation of PC12 cel s into neuron-like cel s.
OBJECTIVE:To investigate the feasibility of neuronal differentiation of neural stem cel s from septal area of fetal brain induced by NGF-PEG-PLGA-NPs and its influence on PI3K/Akt signaling pathway.
METHODS:According to optimization prescription, NGF-PEG-PLGA-NPs were prepared by multiple emulsion solvent diffusion method. Neural stem cel s were induced to neuronal differentiation in six groups, including control group, NGF group, NGF-PEG-PLGA-NPs group, LY294002 group, LY294002+NGF group and LY294002+NGF-PEG-PLGA-NPs group. Neurons were identified by immunofluorescence, while phosphorylation levels of Akt in PI3K/Akt signaling pathway were detected by western blotting.
RESULTS AND CONCLUSION:The proportions ofβ-Tubulin III-positive neurons in control group, NGF group, NGF-PEG-PLGA-NPs group, LY294002 group, LY294002+NGF group and LY294002+NGF-PEG-PLGA-NPs group were (22.80±2.58)%, (35.80±3.98)%, (35.40±5.77)%, (26.60±3.87)%, (21.20±2.59)%and (25.80±7.22)%, respectively. There were no statistical differences in neuronal differentiation between NGF group and NGF-PEG-PLGA-NPs group (P>0.05), but the ratios of neural differentiation in the two groups were both higher than that in the other four groups (P<0.05). Western blotting results revealed that there were no statistical differences in Akt phosphorylation levels between NGF group and NGF-PEG-PLGA-NPs group (P>0.05), but the phosphorylation levels of Akt were both higher than other four groups (P<0.05). There were also no significant differences between LY294002+NGF and LY294002+NGF-PEG-PLGA-NPs groups and control group (P>0.05), but the phosphorylation levels of Akt were higher than LY294002 group (P<0.05). Results suggest that NGF-PEG-PLGA-NPs promoted neural differentiation of neural stem cel s. The role might be related to increasing phosphorylation levels of Akt in PI3K/Akt signaling pathway.

Objective To explore the causes of postoperative recurrence in patients of nodular goiter,the selection of method for reoperation and the postoperative complications. Methods The clinical data of 278 nodular goiter patients admitted in the first affiliated hospital of Harbin Medical University between 2001 and 2008 were analyzed retrospectively,including the methods and complications for first operation and reoperation. Results In the first operation,79 eases received simple eminectomy and 167 cases received partial lobectomy,accounted for 28.4% and 60.1%,respectively. Unilateral subtotal lobectomy plus contralateral eminectomy was performed in 23 cases and subtotal thyroideetomy was conducted in 9 cases,accounted for 8.3% and 3.2%,respectively. Postoperative complications occurred in one hundred and twenty-three cases,the incidence being 8.2% (23/278). Unilateral subtotal Iobectomy plus contralateral partial iobectomy was reperformed in 37 cases and bilateral subtotal thyroidectomy in 241 cases. Postoperative complications occurred in 12 cases,the incidence being 4.2%(12/278). No postoperative recurrence of nodular goiter was found. Conclusions Recurrence of nodular goiter is closely associated with the scope of previous surgical treatment,and correct operative manipulation may reduce the recurrent rate.

OBJECTIVETo investigate the possible role of valproic acid therapy in the development of the weight gain and hyperinsulinemia of epileptic patients.

METHODSThe weight and fasting insulin levels were measured in 43 epileptic patients treated with valproic acid (VPA) alone and 39 patients with carbamazepine (CBZ) alone for at last 2 years. The body mass index (BMI) and homeostasis model assessment (HOMA) index were studied in the two groups.

RESULTBMI was higher in the VPA-treated group (23.47+/-1.45) than that in the CBZ-treated group (22.27+/-2.10, P<0.05). Fasting insulin level and HOMA index in the VPA group were also higher [(6.64+/-0.79)mU/L and 1.33+/-0.21] than those in the CBZ group [(5.52+/- 0.52)mU/L, P<0.01; 1.15+/-0.12, P<0.01]. While BMI in the VPA group showed no significant correlation with plasma concentration and dose of valproate.

CONCLUSIONVPA therapy is associated with significantly greater weight gain and hyperinsulinemia, suggesting development of insulin resistance.

Adult ; Body Mass Index ; Epilepsy ; drug therapy ; metabolism ; Female ; Humans ; Insulin Resistance ; Male ; Valproic Acid ; adverse effects ; Weight Gain ; drug effects

OBJECTIVETo discuss the optimal immunization dose by observing the immunoprotective effects of different doses of recombinant Schistosoma japonicum (Chinese strain) signaling protein 14-3-3 (rSj14-3-3).

METHODSSj14-3-3 gene was amplified by reverse transcriptase PCR (RT-PCR), subcloned into prokaryotic expression vector pET28a, then transformed into E.coli to express by inducing. Purified rSj14-3-3 was prepared through SDS polyacrylamide gel electrophoresis (SDS-PAGE), electroelution, dialysis, then BALB/c mice were divided into 5 groups and immunized in rSj14-3-3 protein followed by challenging infection (the 1st, 2nd, and 3rd groups were immunized in 50 microg, 100 microg and 300 microg antigen, respectively. The 4th, 5th groups were immunized in Freund's adjuvant and normal saline controls). After 6 weeks of challenging infection, the mice were killed and the worm and egg reduction rates were calculated. And the mice sera in different time were taken to examine the specific anti-Sj14-3-3 IgG.

RESULTSrSj14-3-3 protein was expressed successfully. After immunizing and challenging, worm reduction was found to be 28.20% in the 1st group, 43.10% in the 2nd group, 40.00% in the 3rd group, respectively. Number of eggs in liver tissue was reduced by 41.80%, 57.50%, 55.70%, respectively. Compared the results of the tested groups to the controls, the differences were of significance by t-test (worm reduction rate: t = 6.8 in the 1st group, t = 8.7 in the 2nd group, t = 7.3 in the 3rd group, P < 0.01 in all tested groups. Egg reduction rate at the group's number above: t = 11.23, t = 11.54, t = 7.99, P < 0.01 in all tested groups). As compared the results between the tested groups by chi(2), the differences were of significance between the 1st and the 2nd groups (worm reduction rate: chi(2) = 8.96, P < 0.05; egg reduction rate: chi(2) = 15.69, P < 0.05), between the 1st and the 3rd groups, the differences were also of significance (worm reduction rate: chi(2) = 6.52, P < 0.05; egg reduction rate: chi(2) = 12.52, P < 0.05). The difference was not of significance between the 2nd and the 3rd groups (worm reduction rate: chi(2) = 1.20, P > 0.05; egg reduction rate: chi(2) = 0.93, P > 0.05). In all tested groups, total anti-Sj14-3-3 specific IgG rose markedly. IgG(1) and IgG(2a) subtypes were high, but IgG(2b) and IgG(3) were near the background in four subtypes tested.

CONCLUSIONImmunoprotection of rSj14-3-3 should have some relations with immunization dose, and the protection obtained from immunizing mice by using 100 microg antigen was the best.

14-3-3 Proteins ; administration & dosage ; immunology ; Animals ; Antibodies, Helminth ; immunology ; Antibody Formation ; Antigens, Helminth ; blood ; Female ; Helminth Proteins ; immunology ; Immunoglobulin G ; blood ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins ; Schistosoma japonicum ; genetics ; immunology ; Signal Transduction ; Vaccination

OBJECTIVETo compare clinical outcomes between two suturing methods using non absorbable materials through drilling the bone and suturing anchors for the treatment of complete rupture of the deltoid ligament.

METHODSFrom January 2009 to January 2013, 58 hospitalized patients with ankle fracture combined with complete rupture of the deltoid ligament were treated with suturing using non absorbable materials through drilling the bone or suturing anchors. There were 29 patients who received suturing treatments using non absorbable materials through drilling the bone (Group A), including 18 males and 11 females, with an average age of (39.76 +/- 11.81) years old. According to the Lauge-Hansen classification, 12 patients had supination external rotation (SER) injuries with IV degree, 5 patients had pronation external rotation (PER) injuries with III degree, 10 patients had PER injuries with IV degrss, and 2 patients had pronation abduction injuries with III degree. There were 29 patients who received treatments with suturing using anchors (Group B), including 14 males and 15 females, with an average age of (41.79 +/- 13.28) years old. According to the Lauge-Hansen classification,9 patients had SER injuries with IV degree, 6 patients had PER injuries with III degree,13 patients had PER injuries with IV degree, and 1 patient had pronation abduction injuries with III degree. All the patients were treated with open reduction and internal fixation, as well as reconstruction of deltoid ligaments to restore the stability of the medial ankle structures. The clinical examination, imaging evaluation, American society for ankle surgery (AOFAS) ankle-hindfoot score and visual analogue scale (VAS) were used to evaluate the clinical results after operation, and the results of the two groups were compared and analyzed statistically.

RESULTSThe follow-up duration of the 58 patients ranged from 23 to 40 months,with an average of 27.3 months. All the patients had fracture union, and the mean healing time was 12.3 weeks (ranged, 10 to 17 weeks). There were no incision complications and ankle instability. There were no significant differences between two groups in AOFAS (P=0.666) and the VAS (P=0.905).

CONCLUSIONTreatments of complete rupture of the deltiod ligaments with the two suturing methods get similar good clinical effects, but the suturing using non absorbable materials through drilling the bone has several advantages such as reducing the financial burden of patients, saving social medical resources and avoiding the shortcoming in difficult removal of anchor suture.

Adolescent ; Adult ; Ankle Fractures ; surgery ; Ankle Injuries ; surgery ; Ankle Joint ; surgery ; Case-Control Studies ; Female ; Fracture Fixation, Internal ; Humans ; Lateral Ligament, Ankle ; injuries ; surgery ; Male ; Middle Aged ; Young Adult

Objective To compare the diagnostic value of myocardial perfusion imaging (MPI) and 64 multi-slice spiral CT (64-MSCT) for coronary artery disease (CAD). Methods Fifty-two patients with suspected or known CAD were included in the study. Each patient underwent both stress and rest MPI,MSCT as well as conventional coronary angiography (CAG) within 1 month. The stress and rest MPI were scored by a 5-grade criteria (0 ～ 4) based on 17 coronary artery segments. The difference between summed stress and rest scores ＞ 1 was defined as myocardial ischemia. Stenosis in one main vessel or one main branch of the main vessel ≥50% was defined as myocardial ischemia by MSCT. CAG was used as the reference for comparison. Statistical analysis was performed using SPSS 13. 0 software. Kappa value was used to test the accordance of MPI and MSCT results. X2 test was used to evaluate the difference between MPI and MSCT results. Results The patient-based sensitivity, specificity, positive and negative predictive values and accuracy of MPI and MSCT for the diagnosis of CAD were 86.7% (26/30), 77.3% ( 17/22),83.9% (26/31), 81.0% ( 17/21), 82.7% (43/52) and 83.3% ( 25/30), 86.4% ( 19/22), 89.3%( 25/28), 79.2% ( 19/24), 84.6% (44/52), respectively. The vessel-based sensitivity, specificity, positive and negative predictive values and accuracy of MPI and MSCT were 74.5% (38/51), 81.0% (85/105 ), 65.5% (38/58), 86.7% ( 85/98), 78.8% ( 123/156 ) and 90.2% (46/51 ), 88.6% ( 93/105 ),79.3 % (46/58), 94.9% (93/98), 89.1% ( 139/156), respectively. There was no statistically significant difference between MPI and MSCT for either patient or lesion-based diagnosis (X2 =0.44, 0.21, both P ＞0.05 ). 96.0% (24/25) patients with both abnormal MPI and MSCT positive were valified by CAG while 83.3% (15/18) patients with both MPI and MSCT negative were excluded by CAG. Conclusions Both MPI and MSCT are reliable diagnostic modalities for CAD. They also provide complementary diagnostic value to each other.

Background The proliferation and migration of vascular endothelial cells is a primary link during angiogenesis.Studies showed that heat shock protein B6 (HspB6) promotes the secretion of multiple angiogenesis-related factors and therefore leads to neovascularization.Understanding the effects of neutralizing HspB6 antibody on the biological behavior of human choroidal vascular endothelial cells has an important significance in the target treatment of choroidal neovacularization diseases.Objective This study was to address the role and mechanism of neutralizing HspB6 antibody in tube formation of human choroidal vascular endothelial cells.Methods Human choroidal vascular endothelial cell line was normally cultured and harvested for total RNA extraction.Expressions of HspB6 mRNA and protein in human choroidal vascular endothelial cells were detected by reverse transcription PCR (RT-PCR) and flow cytometry (FCM).The cells were seeded on 96-well plate covered with matrigel at the density of 2×104/hole.Then the neutralizing HspB6 antibody at the concentration of 100 μg/Land 500 μg/L was added into the medium respectively,and the control cells were set without the addition of HspB6 antibody.The number of capillary tubes was calculated 12 hours after culture by three-dimensional matrigel assay.In addition,0,50,100,500 μg/L of neutralizing HspB6 antibody were added into the cell medium separately for 24hours,cell counting kit-8 (CCK-8) method was employed to assay the inhibitory rate(IR) of the cells.Transwell test was used to count the cell number across chamber membrane for the evaluation of migration ability of the cells.The apoptosis of the cells was assayed by FCM.Results Both HspB6 mRNA and protein were expressed on human choroidal vascular endothelial cells.The number of capillary tube formation of human choroidal vascular endothelial cells was (67.25±5.75),(60.39±6.41) and (39.76±10.73) /field in the 0,100 and 500 μg/L neutralizing HspB6 antibody groups,with significant difference among them (F =10.210,P =0.012),and the tube number was significantly less in the 500 μg/L neutralizing HspB6 antibody group compared with 0 μg/L neutralizing HspB6 group (P =0.005).The IR of neutralizing HspB6 antibody to the cellular proliferation and migration was enhanced with the increases of concentration and time lapse(Fconcentration =7.485,P =0.002 ; Ftime =16.684,P =0.001).The number of the cells through Transwell chamber membrane was 14.0 ± 2.5,11.1 ± 0.8,6.6 ± 0.1,6.7 ± 0.2 in the 0,50,100,500 μg/L neutralizing HspB6 antibody group respectively,and that in the 100 μg/L and 500 μg/L neutralizing HspB6 antibody group was lessened in comparison with the 0 μg/L neutralizing HspB6 antibody group(both at P=0.000).The apoptosis rate of the cells was (22.73 ± 2.53)％ in the neutralizing HspB6 antibody group,which was significantly lower than (13.33±2.08) ％ of the control group (t=4.967,P=0.008).Conclusions Neutralizing HspB6 antibody inhibits capillary tube formation of human choroidal endothelial cells in vitro in dose-and timedependent manner,probably through suppressing the proliferation and migration and promoting the apoptosis of choroidal endothelial cells.

DNA methylation is a frequent change in epigenetics of leukemia. In the development of leukemia, methylation plays an important role in the genetic expression regulation and genetic structure stabilization. Hematopoietic stem cell transplantation (HSCT) and chemotherapy are the common methods to cure leukemia at present. Unfortunately, it is very hard to find suitable donor for transplantation, while the relapse and drug resistance are the unresolved problems in chemotherapy. Because of the reversibility of methylation, the drugs reducing the level of methylation become a new way to cure leukemia. Decitabine is the most common medicament used to reduce the level of methylation. In this article, the methylation and tumor, methylation and hematologic diseases, methylation detection methods, demethylation therapy in leukemia and so on are reviewed.
DNA Methylation ; Humans ; Leukemia