Acute Disease ; Adolescent ; Child ; Child, Preschool ; Drug Resistance, Multiple ; genetics ; Drug Resistance, Neoplasm ; genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Leukemia ; physiopathology ; Male ; Neoplasm Proteins ; genetics ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Vault Ribonucleoprotein Particles ; genetics

Child, Preschool ; Female ; Humans ; Magnetic Resonance Imaging ; Posterior Leukoencephalopathy Syndrome ; diagnosis ; etiology ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; complications

Objective To investigate the expression and significance of Bcl-2 and MDR1 genes in children with acute leukemia. Methods The expressions of Bcl-2 and MDR1 genes in 36 cases of acute leukemia and 10 cases of idiopathic thrombocytopenic purpura in the control group were examined by RT-PCR. Results The expressions of Bcl-2 in the incipient group and relapsed group were higher than that of the control group (P<0.05). While in the incipient group and complete remission group, they were lower than that of the relapsed group (P<0.01). The expression of MDR1 gene in the relapsed group was higher than those of control group, incipient group and complete remission group (P<0.01 or 0.05). There was no difference of MDR1 expression between the incipient group and the control group or the complete remission group and the control group (P>0.05). There was no close relationship between the levels of Bcl-2 or MDR1 and clinical features such as gender, age, initial WBC count, the percent of carcinocytes, hepatomegaly, splenomegaly and lymphadenhypertrophy (P>0.05). The relationship between Bcl-2 and MDR1 genes was not significant (rs=0.308, P>0.05). Conclusions Bcl-2 and MDR1 genes were associated with drug resistance by different mechanisms.

Aim To observe the effect of interventional therapy of 5-fluorouracil(5-Fu), mitomycin C (MMC) and adriamycin (ADM) on solid malignant turmors in association with aterial infusion of NaHCO3.Methods Patients were randomly divided into two groups.With Seldinger technique,through the femoral atery to tumor atery.The patients in the control group were infused by anticarcinoma agents simply ,and patients in the treatment group were initially infused by NaHCO3,and then by NS 30 ml and anticarcinoma agents seperately. Results Partial remission (PR) in the group treated with NaHCO3 and anticarcinoma agents was significantly higher than in the group treated simply with anticarcinoma agents.Conclusion Aterial infusion of NaHCO3 into malignant tumors can increase the efficacy of ADM,MMC and 5-Fu.

BACKGROUNDGambogic acid is a pure active compound isolated from the traditional Chinese medicinal plant gamboge (Garcinia morella Desv.). Based on the preliminary results of a phase I study, this phase IIa study compared the efficacy and safety of different dosage schedules of gambogic acid in patients with advanced malignant tumors.

METHODSPatients with advanced or metastases cancer who had not received any effective routine conventional treatment or who had failed to respond to the existing conventional treatment were randomly assigned to receive either 45 mg/m(2) gambogic acid intravenously from Days 1 to 5 of a 2-week cycle (Group A), or 45 mg/m(2) every other day for a total of five times during a 2-week cycle (Group B). The primary endpoint was objective response rate (ORR).

RESULTSTwenty-one patients assigned to Group A and 26 to Group B were included in the final analysis. The ORRs were 14.3% in Group A and 0% in Group B. It was not possible to analyze the significant difference because one of the values was zero. The disease control rates (DCRs) were 76.2% in Group A and 61.5% in Group B (P = 0.0456). The observed adverse reactions were mostly Grades I and II, and occurred in most patients after administration of the trial drug. There was no significant difference in the incidence of adverse reactions between the two arms.

CONCLUSIONSThe preliminary results of this phase IIa exploratory study suggest that gambogic acid has a favorable safety profile when administered at 45 mg/m(2). The DCR was greater in patients receiving gambogic acid on Days 1 - 5 of a 2-week cycle, but the incidence of adverse reactions was similar irrespective of the administration schedule.

Adult ; Aged ; Antineoplastic Agents, Phytogenic ; administration & dosage ; Female ; Humans ; Injections ; Male ; Middle Aged ; Neoplasms ; drug therapy ; Xanthones ; administration & dosage ; adverse effects

Objective To evaluate the safety and tolerability of continu-ous intravenous infusion of innovative calcium sensitizer piperphent-onamin ( PPTA) at a loading dose and a maintenance dose in healthy vol-unteers.Methods A randomized, open, single-center, phase I clini-cal trial in 11 healthy male and female subjects was conducted.Each subject was intravenously administered with a single loading dose of 0.1 mg· kg -1 for 20 min, and then a maintenance dose of 0.9 mg· kg -1 for 24 h.Safety and tolerance of PPTA were assessed by vital sign , dynamic electrocardiogram monitoring , physical examination , laboratory tests and eye exams, according to which adverse events ( AEs) were identified and recorded.The safety and tolerability were evaluated.Results Vital signs of all subjects were stable , and no QTc interval prolongation was observed during the trial.A total of 13 AEs were reported in 6 subjects , among which 9 AEs were the reflections of the effects of PPTA and all AEs were all relieved without treatment.Conclusion The regimen of in-travenous PPTA loading dose for 20 min and then a maintenance dose for 24 h is safe and tolerable.

BACKGROUNDErythromycin-resistant Streptococcus pneumoniae isolates that causing invasive pneumococcal diseases (IPD) in Chinese children remain uncharacterized. This study aims to identify the resistance genes associated with erythromycin resistance and to determine the genetic relationships of IPD isolates in Chinese children.

METHODSA total of 171 S. pneumoniae strains were isolated from 11 medical centers in China from 2006 to 2008. All the isolates were characterized via serotyping and antibiotic susceptibility determination. The erythromycin-resistant isolates were further characterized via ermB and mefA gene detection, multi-locus sequence typing analysis, and pulsed-field gel electrophoresis.

RESULTSA total of 164 (95.9%) isolates showed resistance to erythromycin, of which 162 strains with high high-level resistance (MIC ≥ 256 µg/ml). A total of 104 (63.4%) isolates carry the ermB gene alone, whereas 59 (36.0%) harbor both ermB and mefA genes. Of the 59 strains, 54 were of serotypes 19A and 19F and were identified as highly clonal and related to the Taiwan(19F)-14 clone.

CONCLUSIONSThe erythromycin resistance rate in IPD isolates is significantly high and is predominantly mediated by the ermB gene. Isolates that carry both ermB and mefA genes are predominantly of serotypes 19A and 19F.

Adolescent ; Anti-Bacterial Agents ; pharmacology ; Child ; Child, Preschool ; Drug Resistance, Bacterial ; Electrophoresis, Gel, Pulsed-Field ; Erythromycin ; pharmacology ; Humans ; Infant ; Multilocus Sequence Typing ; Pneumococcal Infections ; microbiology ; Serotyping ; Streptococcus pneumoniae ; classification ; drug effects ; genetics ; isolation & purification

ObjectiveTo prepare ⁶⁸Ga-labeled magnetic ferrite nanoparticles PET/MRI dual-modal imaging probe and evaluate the possibility of using it as a novel molecular probe for prostate cancer imaging. MethodsUsing superparamagnetic manganese iron oxide nanoparticles as the key component， fibroblast inhibitor and DOTA-NHS ester as the modification，along with chelating the positron radionuclide ⁶⁸Ga， we prepared the nanoprobe ⁶⁸Ga-DOTA-UMFNPs-FAPI-04. Characterization of nanoprobe and analysis of its cytotoxicity， radiochemical purity and stability were performed during the whole process. The observation of the distribution of nanoprobes in normal mice was performed. The effect of nanoprobes on MRI imaging on tumor-bearing mice was analyzed. ResultsAfter purification， the radiochemical purity of probe was 94%， also it had high stability. MRI T2 test showed that its T2 relaxation rate was about 39.02 mM^-1·s^-1. The bio-distribution in the normal mice showed that ⁶⁸Ga-DOTA-UMFNPs- FAPI-04 had a higher uptake in liver and spleen. MRI imaging demonstrated that tumor could be observed clearly after probe injection in 30 minutes. ConclusionsWe have successfully constructed the PET/MRI dual-modal imaging probe ⁶⁸Ga-DOTA-UMFNPs-FAPI-04. It has the characteristics of MRI T2 contrast agent and it also performs well in the MRI imaging of prostate tumors and has the potential of PET imaging. The study provides a new idea for constructing a multi-modal imaging probe for prostate cancer.

BACKGROUNDHepatitis B is an immune response-mediated disease. The aim of this study was to explore the differences of ratios of T-helper (Th) 2 cells to Th1 cells and cytokine levels in acute hepatitis B (AHB) patients and chronic hepatitis B virus (HBV)-infected patients in immune-tolerance and immune-active phases.

METHODSThirty chronic HBV-infected patients in the immune-tolerant phase (IT group) and 50 chronic hepatitis B patients in the immune-active (clearance) phase (IC group), 32 AHB patients (AHB group), and 13 healthy individuals (HI group) were enrolled in the study. Th cell proportions in peripheral blood, cytokine levels in plasma, and serum levels of HBV DNA, hepatitis B surface antigen, and hepatitis B e antigen were detected.

RESULTSThe Th1 cell percentage and Th2/Th1 ratio in the HBV infection group (including IT, IC, and AHB groups) were significantly different from those in HI group (24.10% ± 8.66% and 1.72 ± 0.61 vs. 15.16% ± 4.34% and 2.40 ± 0.74, respectively; all P < 0.001). However, there were no differences in the Th1 cell percentages and Th2/Th1 ratios among the IT, IC, and AHB groups. In HBV infection group, the median levels of Flt3 ligand (Flt3L), interferon (IFN)-γ, and interleukin (IL)-17A were significantly lower than those in HI group (29.26 pg/ml, 33.72 pg/ml, and 12.27 pg/ml vs. 108.54 pg/ml, 66.48 pg/ml, and 35.96 pg/ml, respectively; all P < 0.05). IFN-α2, IL-10, and transforming growth factor (TGF)-β2 median levels in hepatitis group (including patients in AHB and IC groups) were significantly higher than those in IT group (40.14 pg/ml, 13.58 pg/ml, and 557.41 pg/ml vs. 16.74 pg/ml, 6.80 pg/ml, and 419.01 pg/ml, respectively; all P < 0.05), while patients in hepatitis group had significant lower Flt3L level than IT patients (30.77 vs. 59.96 pg/ml, P = 0.021). Compared with IC group, patients in AHB group had significant higher median levels of IL-10, TGF-β1, and TGF-β2 (22.77 pg/ml, 10,447.00 pg/ml, and 782.28 pg/ml vs. 8.66 pg/ml, 3755.50 pg/ml, and 482.87 pg/ml, respectively; all P < 0.05).

CONCLUSIONSCompared with chronic HBV-infected patients in immune-tolerance phase, chronic HBV-infected patients in immune-active phase and AHB patients had similar Th2/Th1 ratios, significantly higher levels of IFN-α2, IL-10, and TGF-β. AHB patients had significantly higher IL-10 and TGF-β levels than chronic HBV-infected patients in immune-active phase.

OBJECTIVETo explore the predictive value of baseline HBsAg level and early response for HBsAg loss in patients with HBeAg-positive chronic hepatitis B during pegylated interferon alpha-2a treatment.

METHODSA total of 121 patients with HBeAg-positive chronic hepatitis B who achieved HBsAg loss were enrolled; all patients were treated with PEG-IFNα-2a 180 μg/week. Serum HBV DNA and serological indicators (HBsAg, anti-HBs, HBeAg, and anti-HBe) were determined before and every 3 months during treatment.

RESULTSThe median treatment time for HBsAg loss was 84 weeks (7-273 weeks), and 74.38% (90 cases) of the patients needed extended treatment (> 48 weeks). The correlation between baseline HBsAg levels and the treatment time of HBsAg loss was significant (B = 14.465, t = 2.342, P = 0.021). Baseline HBsAg levels together with the decline range of HBsAg at 24 weeks significantly correlated with the treatment time of HBsAg loss (B = 29.862, t = 4.890, P = 0.000 and B = 27.993, t = 27.993, P = 0.005).

CONCLUSIONBaseline HBsAg levels and extended therapy are critical steps toward HBsAg loss. Baseline HBsAg levels together with early response determined the treatment time of HBsAg loss in patients with HBeAg-positive chronic hepatitis B during pegylated interferon alpha-2a treatment.

Adolescent ; Adult ; Antiviral Agents ; therapeutic use ; Child ; Child, Preschool ; DNA, Viral ; blood ; Drug Administration Schedule ; Female ; Hepatitis B Surface Antigens ; blood ; Hepatitis B e Antigens ; blood ; Hepatitis B, Chronic ; blood ; drug therapy ; Humans ; Interferon-alpha ; administration & dosage ; therapeutic use ; Male ; Middle Aged ; Polyethylene Glycols ; administration & dosage ; therapeutic use ; Recombinant Proteins ; administration & dosage ; therapeutic use ; Retrospective Studies ; Young Adult