OBJECTIVETo investigate the therapeutic effects of hemin, an inducer of heme oxygenase, in a rat model of gestational hypertension and explore the possible mechanism.

METHODSEighteen pregnant SD rats at day 12 of gestation were randomized equally into gestational hypertension model group, hemin treatment group, and normal pregnancy (control) group. In the former two groups, the rats were subjected to daily nitro-L-arginine methyl ester (L-NAME, 80 mg/kg) gavage since gestational day 14 for 7 consecutive days to induce gestational hypertension; saline was administered in the same manner in the control rats. The rats in hemin group received daily intraperitoneal injection of hemin (30 mg/kg) starting from gestational day 16. HO activity and carboxyhemoglobin (COHb) level in rat placental tissue were detected with spectrophotometric method, and soluble vascular endothelial growth factor receptor-1 (sFlt-1) and vascular endothelial growth factor (VEGF) level in the placental tissue homogenate supernatant were detected using ELSIA.

RESULTSAt gestational day 20, the blood pressure and 24-h urinary protein were significantly higher in the model group than in the other two groups (P<0.05), and were higher in hemin group than in the control group (P<0.05); HO activity and COHb content in the placenta tissue were the lowest in the model group (P<0.05), and was lower in hemin group than in the control group (P<0.05). The level of sFlt-1 was significantly higher and VEGF level significantly lower in the model group than in the other two groups (P<0.05); sFlt-1 level remained higher and VEGF lower in hemin group than in the control group (P<0.05).

CONCLUSIONHemin can reduce blood pressure and urinary protein in rats with gestational hypertension possibly by up-regulating HO activity, enhancing carbon monoxide production, reducing sFlt-1 and increasing VEGF in the placental tissue.

Animals ; Blood Pressure ; Carbon Monoxide ; metabolism ; Disease Models, Animal ; Female ; Heme Oxygenase (Decyclizing) ; Hemin ; pharmacology ; Hypertension, Pregnancy-Induced ; drug therapy ; Placenta ; drug effects ; metabolism ; Pregnancy ; Rats ; Rats, Sprague-Dawley ; Vascular Endothelial Growth Factor A ; metabolism ; Vascular Endothelial Growth Factor Receptor-1 ; metabolism

OBJECTIVETo summarize the clinical features and to evaluate outcomes and to assess therapeutic effects in 34 children and adolescents with Hodgkin lymphoma treated with risk-adapted combination chemotherapy and low-dose, involved-field radiation therapy (IFRT) in China.

METHODFrom January 2003 to April 2009, 34 hospitalized children with Hodgkin lymphoma were enrolled into the BCH-HL 2003 protocol (revised CCG 5942) in our hospital. Pathological samples were reviewed centrally and classified based on the World Health Organization guidelines. Staging was based on clinical evaluation and was defined by the Ann Arbor staging system. The 34 patients were treated according to the different risk factors in three treatment groups (standard, intermediate, and high risk), and received risk-adapted combination chemotherapy and IFRT. All analyses were calculated by the statistical program SPSS.

RESULTOf the 34 Hodgkin lymphoma patients, 28 were male and 6 were female. The median age was 8.7 years (range from 4 years to 15 years) at the time of diagnosis. In terms of clinical presentation, 53% had bulky lymph nodes, 47.1% had more than 4 node regions involved and 44% had "B" symptoms at presentation. The distribution for stage of disease was 0% for Stage I, 21% for Stage II, 35% for Stage III and 44% for Stage IV disease. All patients had classical histology consisting of three different sub-discipline: 22 cases of mixed cellularity (64.7%). In pathological samples of 25 cases there was EBV encoded RNA (EBER) or latent membrane protein (LMP) staining. The overall survival (OS) was 100% and the 5-year event-free survival was 94.1% with a median follow-up of (26.1 ± 16.3) months. Two patients had early relapse after treatment was finished. Organ toxicity was limited to hematological grades III and IV at rates of 40% and 71% respectively.

CONCLUSIONChildhood Hodgkin lymphoma in our study was more frequently seen in male school aged children. Combined-modality therapy using risk-adapted chemotherapy with radiation is effective and well tolerated. The overall prognosis was good.

Adolescent ; Child ; Child, Preschool ; Combined Modality Therapy ; Female ; Hodgkin Disease ; therapy ; Humans ; Male ; Risk Factors ; Treatment Outcome

OBJECTIVETo study the responses of peginterferon-alpha 2a antiviral therapy in chronic hepatitis B (CHB) patients.

METHODSOne hundred two CHB patients with their serum ALT values higher than 2x the upper limit of the normal (ULN) were divided into a HBeAg-positive and a HBeAg-negative group. All patients were treated with peginterferon-alpha 2a by subcutaneous injection (180 microgram once weekly). After treatment for 6 months, patients without a defined therapeutic response were dropped from the treatment group; the others completed a 12 month therapy. The sustained response and the antiviral effect of the treatment were assessed at the end of the therapy. To investigate the possible impact factors of the response to peginterferon-alpha 2a, we studied the therapeutic response of patients with different serum ALT levels, inflammation grades of liver histology, stages of fibrosis, and HBV viral load levels.

RESULTS(1) There was no statistical difference of the rates of response at the end of treatment and 6, 12, 18, 24 and 30 months after the cessation of therapy between the HBeAg-positive and the HBeAg-negative groups. (2) In the HBeAg-positive group, the rates of response of patients with serum ALT values>3*ULN were significantly higher than those with serum ALT values less than 3*ULN (x2=4.40). However, no statistical difference of serum ALT levels was found in the HBeAg-negative group. (3) In both HBeAg-positive and HBeAg-negative groups, no difference was revealed in the rates of response among patients with different levels of HBV viral loads. (4) In the HBeAg-positive group, patients with more severe liver inflammation histologically (G3 and G4) had significantly higher response rates than those with milder inflammation (G1 and G2) (x2=4.19), but no similar statistical differences were found in the HBeAg-negative group. Moreover, there was no difference in the rates of response among patients in different stages of liver fibrosis in both HBeAg-positive and HBeAg-negative groups.

CONCLUSIONSSimilar rates of response and sustained virological response to the peginterferon-alpha 2a treatment can be achieved in both HBeAg-positive and HBeAg-negative patients. Hepatic fibrosis is not a predictor of poor therapeutic response. For HBeAg-positive patients, more severe liver inflammation identified with liver biopsies (G3 or G4) and high serum ALT values (more than 3*ULN) can be considered as predictors of a good therapeutic response.

Adolescent ; Adult ; Antiviral Agents ; therapeutic use ; Female ; Hepatitis B, Chronic ; drug therapy ; pathology ; Humans ; Interferon-alpha ; therapeutic use ; Liver ; pathology ; Male ; Middle Aged ; Polyethylene Glycols ; therapeutic use ; Recombinant Proteins ; Young Adult

Objective To conduct a microbiological and parasitological investigation of experimental minipigs in Guangdong province. Methods Four major experimental minipig production units in Guangdong province were included in this investigation. Samples were taken from a total of 154 pigs of 4 brreds, i. e. , Bama minipigs, Juema minipigs, Tibet minipigs and Wuzhishan minipigs. Pig fur, scales, serum, rectal swabs and feces samples were collected for detection of 20 pathogens. The data were analyzed and compared among the production units and breeds. Results Mixed infections were detected in all the four institutions. The infection rates of 7 pathogens were rather high: Streptococcus suis type 2 (50. 7%), Actinobacillus pleuropneumoniae (40. 3%), Mycoplasma hyopneumoniae (100%), Japanese encephalitis virus (41. 3%), porcine circovirus type 2 (74. 8%), porcine transmissible gastroenteritis virus (73. 8%),gastroenteritis virus (44. 7%). Porcine parvovirus (26. 0%), pseudorabies virus(15. 6%) and intestinal worms (3. 2%) were also detected in some animals. The immune qualified rates of classical swine fever virus (62. 8%) and foot-and-mouth disease virus (35. 8%) were rather low. The immune qualified rate of pseudorabies virus was as high as 98. 4%. Besides, Salmonella, Brucella, swine dysentery snake like spirochetes, dermatophytes, influenza virus. Toxoplasma gondii, ectoparasites, and coccidia were not detected. Conclusions The results of this investigation indicate that epidemiological quality control of pathogens in experimental minipigs and efforts to establish high grade minipig population in Guangdong province remain to be strengthened. Our study also provides a basis for revision of local and even national standards for experimental minipigs.

To investigate the activity of CKLF1 on the proliferation and differentiation of bone marrow cells. Methods Human low density bone marrow cells and mouse bone marrow cells were plated in 96-well microplate and supernatants from transfected COS-7 cell culture were added. The cell proliferation was assayed by MTT method after 5 days incubation. The enhancing effect of CKLF1 on the colony forma tion of human hematopoietic progenitor cells was identified in semi-solid culture. Results CKLF1 has obvi ous enhancing effect on both human and mouse bone marrow cells, it can stimulate the colony formation of human hematopoietic stem cells and has synergistic action with GM-CSF. Conclusion CKLF1 can pro mote the proliferation and differentiation of bone marrow cells.

OBJECTIVEWe previously showed that introduction of a normal, neomycin-tagged human chromosome 8 reduced the metastatic capacity of C5F rat liver cancer cell line, which had high metastatic potential without affecting tumorigenicity, suggesting the presence of one or more metastasis suppressor genes encoded on human chromosome 8. We proceeded to define further the region harboring the metastasis suppressor gene(s) and to determine the random loss of human chromosome 8 by PCR amplification of sequence tag site (STS) markers.

METHODSThe national Center for Biotechnology Information (NCBI) databases were used as references of the relative genetic distances of the STS markers. C5F genomic DNA and A9/neo8 genomic DNA were used as negative and positive controls for chromosome 8 amplification, respectively. Genomic DNA was isolated and quantified from cultured hybrid clones (A9/C5F-1 and A9/C5F-2 microcell hybrid clones served as metastasis-unsuppressed groups; A9/C5F-4, A9/C5F-8 and A9/C5F-10 microcell hybrid clones served as metastasis suppressed groups). STS-PCR products were separated by electrophoresis through 2% agarose gel.

RESULTSMetastasis-suppressed microcell hybrid clones (A9/C5F-4, A9/C5F-8 and A9/C5F-10) conserved STS markers between D8S542 --> D8S1973 (8p21.1-23.1). In contrast, metastasis-unsuppressed clones (A9/C5F-1 and A9/C5F-2) lacked several markers in this region. In attempts to refine the region retained in the microcell suppressed clones, more densely spaced STS markers in the human chromosome 8p21.1-23.1 were used. We found that the metastasis-suppressed clones retained 18cM region between D8S542 and D8S1973 (8P21.1-23.1), where as the metastasis-unsuppressed clones lacked the region.

CONCLUSIONOur results suggest that a metastasis suppressor gene is located within the interval between D8S542 and D8S1973 on human chromosome 8p21.1-23.1.

Carcinoma, Hepatocellular ; genetics ; Cell Line ; Cell Line, Tumor ; Chromosome Mapping ; Chromosomes, Human, Pair 8 ; genetics ; Fibroblasts ; cytology ; Genes, Tumor Suppressor ; Humans ; In Situ Hybridization, Fluorescence ; Liver Neoplasms ; genetics ; Neoplasm Metastasis ; Sequence Tagged Sites

OBJECTIVETo study the histopathologic changes of primary brain stem injury and to investigate their significance in the diagnosis of primary brain stem injury.

METHODSSixty-five autopsy cases died of primary brain stem injury and other diseases were enrolled into this study. The cases were subdivided into brain stem injury group (n = 25) and control group (including 20 cases died of cardiovascular disease and 20 cases died of non-cardiovascular diseases). The brain stem tissue sections were stained with hematoxylin-eosin and silver impregnation techniques. Immunohisto chemical study for glial fibrillary acidic protein, neurofilament, amyloid-beta and myelin basic protein was carried out. The widest cross diameters of 10 axons highlighted by immunostaining were measured in each low power field (x 100) through light miscroscopy in all the cases studied.

RESULTSIn comparing with that of the control group, there were differences in the degree of contusion lesion, reactive astrocytosis, edema and pathologic changes of neuronal cells present in the brain stem injury group and was statistically significant (P < 0.05). The axons locating in the brain stem injury group showed a distinctive histology by the appearance of significantly larger diameters (P < 0.05).

CONCLUSIONSPrimary brain stem injury demonstrates certain distinctive histopathologic changes and measurement of axonal diameters provides an additional quantitative index useful in autopsy diagnosis.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Amyloid beta-Peptides ; metabolism ; Axons ; metabolism ; pathology ; Brain Injuries ; metabolism ; pathology ; Brain Stem ; injuries ; metabolism ; pathology ; Female ; Glial Fibrillary Acidic Protein ; metabolism ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Myelin Basic Protein ; metabolism ; Neurofilament Proteins ; metabolism ; Young Adult

OBJECTIVETo analyze the clinical features and prognostic factors of children's anaplastic large cell lymphoma (ALCL), summarize the therapeutic effect and toxicities.

METHODA total of 38 ALCL patients admitted to Beijing Children's Hospital from Jan. 2003 to Apr. 2010 were treated with BCH-ALCL-2003 regimen (modified from HK-ALCL-2000).

RESULTThirty-four cases were ALK(+), male:female ratio = 2.16:1. The median age was 9 years; 86.8% had B symptoms. 94.7% evolved to Stage III and IV on admission. The median follow-up duration was 48 months (12 to 99 months). Median event-free survival (EFS) time was 43 months. Thirty-four patients (89.5%) achieved a remission. The disease relapsed in 3 patients within 20 months after diagnosis. Estimated 4-year EFS was (81.2 ± 6.4)%, estimated 4-year overall survival (OS) rate was (86.4 ± 5.7)%. Univariate analysis indicated that the unfavorable prognostic factors included: more than 3 extra nodal involvement, hepatosplenomegaly (> 3 cm), elevated lactate dehydrogenase (LDH), stage IV, hemophagocytosis in bone marrow, and age < 3 years. The major toxicity was myelosuppression and mucositis. no chemotherapy related death occurred.

CONCLUSION(1) Childhood ALCL patients often have B symptoms and extranodal involvement. (2) In the study, therapeutic effects was good. The disease relapsed mostly within the first 2 years, maintenance therapy with vinblastine is necessary. (3) The regimen is safe to patients.

Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Lymphoma, Large-Cell, Anaplastic ; diagnosis ; therapy ; Male ; Prognosis ; Treatment Outcome

OBJECTIVESTo study the relationship between the expression level of DLC-1 mRNA (located in 8p) and the invasion/metastasis of human hepatocellular carcinoma (HCC).

METHODSFifty-one surgical specimens of human HCC were divided into high-invasive and low invasive groups according to their clinicopathological features. DLC-1 mRNA expression was studied in the 51 HCC specimens as well as 5 different metastasis potential cell lines using real-time quantitative PCR (RQ-PCR).

RESULTSThe expression level of DLC-1 mRNA in HCC specimens with high invasiveness was significantly lower than that with low invasiveness (P < 0.05). The expression levels of DLC-1 mRNA were significantly different between non-metastatic (Hep3B and HepG2) and metastatic (MHCC97-H, MHCC97-L and HCCLM3) cell lines (P < 0.05). From MHCC97-L to HCCLM3, with an increase of invasiveness and metastatic potentials, the expression level of DLC-1 decreased correspondingly, and its expression level in HCCLM3 was significantly lower than that in MHCC97-L (P < 0.01).

CONCLUSIONThe expression of DLC-1 mRNA may play an important role in inhibiting the invasiveness and metastasis of HCC.

Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Line, Tumor ; GTPase-Activating Proteins ; Gene Expression Regulation, Neoplastic ; Humans ; Liver Neoplasms ; metabolism ; pathology ; Mutagenesis, Site-Directed ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; RNA, Messenger ; biosynthesis ; genetics ; Tumor Suppressor Proteins ; biosynthesis ; genetics

OBJECTIVETo study the tumor cell killing function of T lymphocytes stimulated by dendritic cells (DC) and to analyze the differences of protein contents of exosomes in each type of cell.

METHODSThe exosomes of hepatic cell lines with high (P group) or low (F group) metastatic potentials were isolated by a process of four-step centrifugation and the collected exosomes were observed under an electron microscope (EM). The tumor cell killing experiment was performed by adding T lymphocytes activated by DC loaded with exosomes from corresponding P and F group cells and was studied using 3H-TdR experiments. The proteomic analysis was performed by surface-enhanced laser desorption/ ionization time of flight mass spectrometry (SELDI-TOF-MS ) on the exosomes of P and F group cells.

RESULTSThe density distribution and content of exosomes in the P group were not equal to those in the F group observed by EM. The CD80, CD86, MHC-I and MHC-II in the P group were 64.27+5.00, 44.89+10.11, 84.35+19.89 and 59.03+19.37, and those in the F group were 71.53+4.85, 50.01+9.50, 80.68+29.87 and 58.86+21.11, respectively (P>0.05, compared with the control group). The counts per minute value in the P group was 528.40+179.06 and 78.80+24.44 in the F group after being loaded with exosomes (P<0.01, compared with the control group). There were significant differences between the proteins in the exosomes of hepatic cancer cell lines with high or low metastatic potentials.

CONCLUSIONExosomes have potential values of application in immunotherapy and in biotherapy for recurrences and metastases of hepatic carcinomas.

Animals ; Carcinoma, Hepatocellular ; metabolism ; pathology ; Cell Line, Tumor ; Dendritic Cells ; immunology ; metabolism ; Exosomes ; Liver Neoplasms ; metabolism ; pathology ; Lymphocyte Activation ; Male ; Mice ; Mice, Inbred BALB C ; T-Lymphocytes ; immunology ; metabolism