OBJECTIVETo investigate the absolute bioavailability of caffeic acid in rats and its intestinal absorption properties.

METHODThe absolute bioavailability (Fabs) of caffeic acid was obtained after iv (2 mg x kg(-1)) or ig (10 mg x kg(-1)) administration to rats. The intestinal absorption of caffeic acid was explored by the recirculating vascularly perfused rat intestinal preparation. Caco-2 cell model was applied to measure the permeability of caffeic acid from apical to basolateral said (A-B) and from basolateral to apical said (B-A).

RESULTA two-compartment pharmacokinetic model was best to describe the pharmacokinetics of caffeic acid following iv or ig administration. The Fabs of caffeic acid was 14. 7% , and its intestinal absorption was 12.4%. The values of Papp A-->B and Papp B-->A of caffeic acid were retained stable while its concentration was changed. The efflux ratio values in this study surveyed were above 2.0, and suggesting caffeic acid was active transport.

CONCLUSIONCaffeic acid was shown to have poor permeability across the Caco-2 cells, low intestinal absorption and low oral bioavailability in rats.

Animals ; Biological Availability ; Caco-2 Cells ; Caffeic Acids ; metabolism ; pharmacokinetics ; Humans ; Intestinal Absorption ; Male ; Rats ; Rats, Sprague-Dawley

Cancer incidence(1950 ～ 1995) among 27 011 medical X-ray workers in comparison with 25 782non X-ray medical specialists between 1950 and 1980 in China was investigated. The average cumulative dose received by the X-ray workers also reconstructed by retrospective dosimetry methods. Significant cancer risk was seen among medical X-ray workers(RR = 1.2). Significantly elevated risks were found in leukemia, cancer of skin, female breast, lung, liver, bladder and esophagus, the RRs were 2. 2, 4. 1,1.3, 1.2, 1.2, 1.8 and 2. 7 respectively. The patterns of cancer risk were associated with years since beginning of X-ray work, age and calendar year of initial employment and cumulative dose suggest that the risks of leukemia, skin cancer and female breast cancer, possibly thyroid cancer were related to occupational exposure to X-rays. A significant cancer risk could be induced by prolonged exposure to low dose ionizing radiation when the cumulative dose reached a certain level.

Objective To investigate the specific T cell subpopulation and the relationship with facial motoneuron in immune deficiency mouse model with facial nerve paralysis, so as to find information for new strategy of facial palsy treatment. Methods Firstly, purifying the CD4+ T cell from wild type mouse and reestablishing the immune function of nude mouse by infusing the CD4+ T cell through the tail vein a week before the surgery. Then the all nude mouse(BALB/c background)and wild type mouse(BALB/c background)were subjected to a right facial nerve axotomy. Then the mouse was studied by application and assessment with fluorogold retrotraeer at specific time. After collecting the slices of brain stem three days post the operation,the facial motoneurons was observed under fluorescence microscope, then analyzed and counted with the software Image Pro Plus5.1. Results The number of survival facial motoneuron in the group with CD4+ T cell transplantation and control group was(3444.5±84.2,-x±s)and(3013.2±65.3)respectively. There was significant difference of the number of survival facial motoneurons between nude mouse transplanted with CD4+ T cell and PBS at three days post the operation(t=5.52,P=0.0003).But there was no significant difference of survival facial motoneurons between nude mouse transplanted with CD4+ T cell and wild type mouse three days post the operation(t=0.49,P=0.6347). It was the transplantation of CD4+ T cell that rescued the survival facial motoneuron to the level of wild type.Conclusions CD4+ T cell have the ability to rescue the iniuring facial motoneuron from death. It may suggest that there is a critical role of the specific T cell subpopulation in facial nerve repair and regeneration.

OBJECTIVETo evaluate the protective efficacy of plague subunit vaccine, BALB/c mice, guinea pigs and rabbits were used in this study.

METHODSGroups of mice (10 per group), guinea pigs (14 per group) and rabbits (6 per group) were immunized with F1 + rV270 vaccine, EV76 vaccine and alum adjuvant by intramuscular route, respectively. Serum antibody titres of mice, guinea pigs and rabbits were determined by ELISA and the immunized animals were challenged with 10(6) CFU of Y. pestis strain 141 at the 8th week after the primary immunization.

RESULTSThe immunized mice, guinea pigs or rabbits with subunit vaccine developed anti-F1 IgG titre of 41 587.3 +/- 2.1, 11 543.7 +/- 2.1 or 522.4 +/- 22.4 and elicited statistical anti-F1 IgG titre difference among them (F = 17.58, P < 0.01). The immunized mice, guinea pigs or rabbits with subunit vaccine had anti-rV270 IgG titre of 15 748.7 +/- 1.6, 12.6 +/- 1.4 or 1648.0 +/- 5.0 and induced statistical anti-rV270 IgG titre difference among them (F value was 16.34, P < 0.01). There was significant anti-F1 IgG titre difference among mice, guinea pigs and rabbits immunized with EV76 vaccine that developed anti-F1 IgG titre of 913.4 +/- 4.5, 937.0 +/- 2.0 or 342.0 +/- 12.0 (F = 23.67, P < 0.01), whereas the immunized mice, guinea pigs and rabbits with EV76 vaccine developed anti-rV270 IgG titre of 12.0 +/- 1.0, 447.0 +/- 10.0, 40.0 +/- 11.0 and there was no anti-rV270 IgG titre difference between them (F = 2.20, P = 0.1314). The immunized mice with subunit vaccine developed significantly higher anti-F1 IgG titres than immunized guinea pigs and rabbits (q value was 30.57 and 19.04, respectively, P < 0.01), and there were no anti-F1 IgG titre differences between the immunized guinea pigs and rabbits (q = 0.04, P = 0.8485). The immunized mice with subunit vaccine developed significantly higher anti-rV270 IgG titres than immunized guinea pigs and rabbits (q value was 27.10 and 19.49, respectively, P < 0.01), and there were no anti-rV270 IgG titre differences between the immunized guinea pigs and rabbits with the subunit vaccine (q = 0.25, P = 0.6187). The immunized mice with EV76 elicited higher anti-F1 IgG titres than immunized guinea pigs and rabbits (q value was 40.67 and 29.10, respectively, P < 0.01), whereas there was no difference of F1 IgG titer between immunized guinea pigs and rabbits (q = 0.06, P = 0.8098). The immunized mice, guinea pigs and rabbits with subunit vaccine provided 100% (10/10), 86% (12/14) and 100% (5/5) protection against 10(6) CFU Y. pestis of challenge, respectively. The immunized mice, guinea pigs and rabbits with EV76 vaccine gave 100% (6/6), 93% (13/14) and 100% (6/6) protection against 10(6) CFU Y. pestis of challenge respectively.

CONCLUSIONBALB/c mice is the best small animal model for valuation of protective efficacy of plague subunit vaccine. The guinea pigs showed a high individual variation for this purpose. The rabbits can be used as an alternative model for evaluating plague subunit vaccine.

Animals ; Antibodies, Bacterial ; blood ; Dose-Response Relationship, Immunologic ; Female ; Guinea Pigs ; Immunization ; Immunoglobulin G ; blood ; Mice ; Mice, Inbred BALB C ; Models, Animal ; Plague ; prevention & control ; Plague Vaccine ; immunology ; Rabbits ; Vaccines, Subunit ; immunology

BACKGROUNDThere were few studies on the relation between changes in libido and incidence of stroke recurrence. The aim of this study was to investigate the relationship between libido decrease at 2 weeks after stroke and recurrent stroke at 1-year.

METHODSIt is a multi-centered, prospective cohort study. The 14 th item of the Hamilton Depression Rating Scale-17 was used to evaluate changes of libido in poststroke patients at 2 weeks. Stroke recurrence was defined as an aggravation of former neurological functional deficit, new local or overall symptoms, or stroke diagnosed at re-admission.

RESULTSAmong 2341 enrolled patients, 1757 patients had completed follow-up data, 533 (30.34%) patients had decreased libido at 2 weeks, and 166 (9.45%) patients had recurrent stroke at 1-year. Multivariate logistic regression analysis showed that, compared with patients with normal libido, the odds ratio (OR) of recurrent stroke in patients with decreased libido was reduced by 41% (OR = 0.59, 95% confidence interval [CI]: 0.40-0.87). The correlation was more prominent among male patients (OR = 0.52, 95% CI: 0.31-0.85) and patients of ≥60 years of age (OR = 0.57, 95% CI: 0.35-0.93).

CONCLUSIONSOne out of three stroke patients in mainland China has decreased libido at 2 weeks after stroke. Decreased libido is a protective factor for stroke recurrence at 1-year, which is more prominent among older male patients.

Aged ; Asian Continental Ancestry Group ; China ; Female ; Humans ; Incidence ; Libido ; physiology ; Male ; Middle Aged ; Prospective Studies ; Risk Factors ; Stroke ; epidemiology

Child ; Correlation of Data ; Flow Cytometry ; Humans ; Immunophenotyping ; Neoplasm, Residual ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis

OBJECTIVETo identify the incidence of PAX5 deletion in childhood B-lineage acute lymphoblastic leukemia (B-ALL) without reproducible chromosomal abnormalities and to investigate the association between PAX5 abnormalities and prognosis of ALL.

METHODSMultiplex ligation-dependent probe amplification was used to determine the copy numbers of PAX5 gene in children newly diagnosed with B-ALL without reproducible chromosomal abnormalities between April 2008 and April 2013 and controls (children with non-hematologic diseases or tumors). The patients were classifiied into deletion group and non-deletion group based on the presence of PAX5 deletion.

RESULTSEighteen (21%) out of 86 children with B-ALL had PAX5 deletion. The deletion group had a significantly higher total white blood cell count at diagnosis than the non-deletion group (P=0.001). The Kaplan-Meier analysis demonstrated that the deletion group had a significantly lower disease-free survival (DFS) rate than the non-deletion group (0.69±0.12 vs 0.90±0.04; P=0.017), but there was no significant difference in the overall survival rate between the two groups (P=0.128). The Cox analysis showed that PAX5 deletion was a risk factor for DFS (P=0.03).

CONCLUSIONSPAX5 deletion is an independent risk factor for DFS in B-ALL children without reproducible chromosomal abnormalities.

Acute Disease ; Adolescent ; Cell Lineage ; Child ; Child, Preschool ; Chromosome Aberrations ; Disease-Free Survival ; Female ; Gene Deletion ; Humans ; Infant ; Male ; PAX5 Transcription Factor ; genetics ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; mortality

OBJECTIVE: To study the association of platelet level at diagnosis with prognosis in children with acute lymphoblastic leukemia (ALL). METHODS: A total of 892 children with ALL who underwent chemotherapy with the CCLG-ALL 2008 regimen were enrolled. According to the platelet count at diagnosis, these children were divided into normal platelet count group (platelet count ≥100×109/L; n=263) and thrombocytopenia group (platelet count <100×10/L; n=629). The thrombocytopenia group was further divided into (50- <100)×10/L (n=243), (20- <50)×10/L (n=263), and <20×10/L (n=123) subgroups. The association of clinical features (sex, age, immunophenotype, and molecular biology) with event-free survival (EFS) and overall survival (OS) was analyzed. RESULTS: Compared with the thrombocytopenia group, the normal platelet count group had significantly lower positive rate of MLL gene rearrangement and recurrence rate (P<0.05), as well as a significantly higher 10-year EFS rate (P<0.05). There was no significant difference in 10-year OS between the two groups (P>0.05). The normal platelet count group still had a significantly higher 10-year EFS rate than the thrombocytopenia group after the children with MLL gene rearrangement were excluded (P<0.05), and there was still no significant difference in 10-year OS between the two groups (P>0.05). The <20×10/L subgroup had significantly lower 10-year EFS and OS rates than the normal platelet count group, the (50- <100)×10/L subgroup, and the (20- <50)×10/L subgroup (P<0.05). After the children with MLL gene rearrangement were excluded, the <20×10/L subgroup still had significantly lower 10-year EFS and OS rates than the normal platelet count group, the (50-<100)×10/L subgroup, and the (20- <50)×10/L subgroup (P<0.05). CONCLUSIONS ALL children with MLL gene rearrangement often have the clinical manifestation of thrombocytopenia. Platelet level at diagnosis is associated with the prognosis of ALL children. The children with normal platelet count have a low recurrence rate and good prognosis, and those with a platelet count of <20×10/L have the worst prognosis.
Child ; Disease-Free Survival ; Humans ; Immunophenotyping ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Prognosis ; Recurrence

OBJECTIVETo study the efficacy and safety of Chinese Childhood Leukemia Group ALL 2008 (CCLG-ALL2008) protocol combined with tyrosine kinase inhibitor (TKI, imatinib) for the treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in children.

METHODSThe clinical data of 53 patients aged less than 15 years when first diagnosed with Ph+ ALL between October 2008 and December 2013 were retrospectively analyzed. The patients were assigned to two groups: HR (n=26) and HR+TKI (n=27). The HR group was treated with CCLG-ALL2008 protocol (for high-risk patients). The HR+TKI group was treated with imatinib in combination with CCLG-ALL2008 protocol (for high-risk patients).

RESULTSThe complete remission rate and chemotherapy induction-related mortality rate in the TKI+HR and HR groups were 100% vs 75% and 0 vs 15%, respectively. The 3-year event-free survival (EFS) rate in the HR group was (6±5)%; the 5-year EFS rate of the TKI+HR group was (52±11)%. Compared with the HR group, the TKI+HR group had no increase in the toxic responses to chemotherapy and had a decrease in the infection rate during the induction period.

CONCLUSIONSApplication of imatinib significantly improves the clinical efficacy in children with Ph+ ALL and has good safety.

Adolescent ; Antineoplastic Agents ; therapeutic use ; Child ; Child, Preschool ; Female ; Humans ; Imatinib Mesylate ; adverse effects ; therapeutic use ; Male ; Philadelphia Chromosome ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; mortality ; Protein Kinase Inhibitors ; therapeutic use

OBJECTIVETo investigate the application of multiplex ligation-dependent probe amplification (MLPA) in the detection of copy number variations (CNVs) in pediatric ETV6/RUNX1-positive acute lymphoblastic leukemia (ALL), to compare this method with conventional karyotype analysis and fluorescence in situ hybridization (FISH), and to evaluate the value of MLPA.

METHODSThe clinical data of 95 children with ETV6/RUNX1-positive ALL who were treated from January 2006 to November 2012 were analyzed retrospectively, including clinical features, results of karyotype analysis, and results of FISH. CNVs were detected with MLPA.

RESULTSCNVs were detected in 73 (77%), and the median number of CNVs was 1 (range 0-6). The CNVs of EBF1, CDKN2A/2B, PAX5, ETV6, RB1, and BTG1 were detected in more than 10% of all the patients. The changes in the chromosome segments carrying the genes with CNVs detected by MLPA were not detected by conventional karyotype analysis. The coincidence rate between the CNVs in ETV6 gene detected by FISH and those detected by MLPA was 66%.

CONCLUSIONSMLPA is an efficient and convenient method to detect CNVs in children with ETV6/RUNX1-positive ALL.

Adolescent ; Child ; Child, Preschool ; Core Binding Factor Alpha 2 Subunit ; analysis ; DNA Copy Number Variations ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Male ; Multiplex Polymerase Chain Reaction ; methods ; Oncogene Proteins, Fusion ; analysis ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics