Objective The factors influencing the dose distribution of intracavitary brachytherapy for moderately advanced and advanced uterine cervical cancer was studied.Methods Ninty-five patients with cervical cancerⅡ～Ⅲb who received radical radiation therapy in our department from Aug,2004 to Nov,2005,were treated with after-loading brachytherapy using,first,the self-designed“Mutipurpose Hori- zontal Transit Table”(MPHTT) for locating and treatment before the intracavitaray brachytherapy proper. The deviation of isodose curve based on A-B reference system,and the dose of deviation was defined by measuring in a practical standard phantom.Results There were significant influence on the deviation of i- sodose curve in pathology and para-metrial infiltration of cervical cancer and operating skill,but negative to clinical stage.The degree of deviation of isodose curve could not be lowered with the increase in sessions of intracavitary brachytherapy.Conclusions It is necessary to perform the locating,by use of mphtt,before the proper brachytherapy for patients with cervical cancer,not only for the identification of the deviation of i- sodose curve,but also to provide the evidence for revising the plan for dose adjustment of conformal radiation therapy in the pelvic cavity.

OBJECTIVETo investigate the effects of dopamine (DA) and metabolite in striatum of Parkinson's disease (PD) rats treated by bone mesenchymal stem cells (MSCs) modified by plasmid pIRESneo-EGFP-BDNF.

METHODpIRESneo-EGFP-BDNF was transfected to MSCs with electroporation. The rat models of PD were set up by 6-OHDA and then divided into four groups randomly, which were Sham group, PD group, BDNF group. The rotating behavior of rat models induced by apomorphine (APO) intraperitoneally which transplanting bone MSCs or MSCs modified by plasmid pIRESneo-EGFP-BDNF through cerebral lateral ventricle after 2, 4 and 8 weeks. The levels of DA, homovanillic acid (HVA), dihydroxy-phenylacetic acid (DOPAC) were measured by high performance liquid chromatography (HPLC) in striatum of each group.

RESULTSThe rotation numbers (r/min) of MSCs group or BDNF group in the 2nd, 4th and 8th week after transplanting were significantly decreased compared with that of PD group (P < 0.05). Those of BDNF group were specially significant compared with those of MSCs group (P < 0.05). The levels of DA, HVA, DOPAC and the ratios of DA/HVA, DA/DOPAC in stratum after PD rats intervened by transplanting cells through cerebral lateral ventricle after eight weeks were increased significantly in BDNF group or MSCs group while compared with PD group, especially in BDNF group.

CONCLUSIONThe behavior of rat with PD was improved significantly by increasing the levels of DA and decreasing metabolic rate of DA in striatum while transplanting BDNF modified bone MSCs through cerebral lateral ventricle.

Animals ; Brain-Derived Neurotrophic Factor ; genetics ; Corpus Striatum ; metabolism ; Disease Models, Animal ; Dopamine ; metabolism ; Genetic Engineering ; Male ; Mesenchymal Stem Cell Transplantation ; Mesenchymal Stromal Cells ; cytology ; metabolism ; Parkinson Disease ; metabolism ; Plasmids ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo retrospectively analyze the effects of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on childhood chronic myelogenous leukemia (CML).

METHODOf the 24 consecutive cases, 16 were boys and 8 were girls. The median age of patients was 12 (3 - 16) years old; 16 cases were in chronic phase (CP) of CML, 1 case in accelerated phase (AP) and 5 cases in blastic phase (BP). Allo-HSCT from HLA identical siblings were performed for 5 cases, HLA haplotype was performed for 14 cases and unrelated allo-HSCT for 5 cases. Twenty-four cases underwent allo-HSCT with conditioning regimen of BUCY. Prophylaxis of graft versus host disease (GVHD) included CsA + MTX plus MMF. The average follow-up was 36 months.

RESULTAll of patients were successfully engrafted. The 5-year overall survival (OS) of the 24 cases was 81%. Four patients died after allo-HSCT including 3 cases in BP from haploidentical donors and 1 case in CP from HLA identical sibling. The 5 cases who received unrelated allo-HSCT have been alive. Among the 10 cases who survived over 5 years, 3 had chronic GVHD.

CONCLUSIONChildren with CML could be treated effectively with allo-HSCT. There were no significant differences among different donors. Transplantation to children with CML should be performed as early as possible. Preparative regimen adjustment before transplantation, the transplantation of associated comorbidities and effective prevention and treatment for CML patients after prolonged graft survival of high quality have important significance.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Cyclophosphamide ; administration & dosage ; Female ; Graft vs Host Disease ; mortality ; prevention & control ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; mortality ; therapy ; Male ; Methotrexate ; administration & dosage ; Retrospective Studies ; Survival Analysis ; Transplantation Conditioning ; methods ; Transplantation, Homologous ; Treatment Outcome

OBJECTIVETo prepare a new Wubei fast-release tablet and study the pharmacokinetics and bioequivalence of self-prepared Wubei fast-release tablet and Wubei powder in Beagle dogs.

METHODWubei fast-release tablet was prepared with direct powder compression. Six Beagle dogs were randomly devided into two groups. They were orally administered with Wubei fast-release tablet and Wubei powder, respectively. Peimine concentrations in human plasma were determined by HPLC-MS/MS after administration. The pharmacokinetic parameters were calculated by DAS 2.0 using a non-compartmental analysis. The bioequivalence of fast-release tablet and powder was evaluated.

RESULTThe main pharmacokinetic parameters of peimine in Wubei fast-release tablet as follows: Cmax (7.4 +/- 2.3) microg x L(-1), AUC(0-t) (59.13 +/- 15.25) microg x L(-1) x h(-1), Tmax (1.5 +/- 0.0) h. The main pharmacokinetic parameters of peimine in Wubei powder as follows: Cmax (8.0 +/- 1.7) microg x L(-1), AUC(0-t) (68.78 +/- 16.27) microg x L(-1) x h(-1), Tmax (1.5 +/- 0.0) h. The 90% confidence interval of InAUC(0-t), and lnCmax of peimine in Wubei fast-release tablet were 95.4% - 104.6%, 90.9% - 109.1% of corresponding parameters of Wubei powder, respectively.

CONCLUSIONThe self-prepared Wubei fast-release tablet and Wubei powder were bioequivalent. And the self-prepared Wubei fast-release tablet had simple production process, easy administration.

Animals ; Dogs ; Drug Delivery Systems ; Drug Stability ; Drugs, Chinese Herbal ; chemistry ; metabolism ; pharmacokinetics ; Female ; Humans ; Sodium Bicarbonate ; chemistry ; Tablets ; Therapeutic Equivalency

This study is to investigate the binding capability of lidamycin apoprotein (LDP), an enediyne-associated apoprotein of the chromoprotein antitumor antibiotic family, to human breast cancer and normal tissues, the correlation of LDP binding capability to human breast cancer tissues and the expression of tumor therapeutic targets such as VEGF and HER2. In this study, the binding capability of LDP to human breast cancer tissues was detected with tissue microarray. The correlation study of LDP binding capability to human breast tumor tissues and relevant therapeutic targets was performed on breast cancer tissue microarrays. Immunocytochemical examination was used to detect the binding capability of LDP to human breast carcinoma MCF-7 cells. As a result, tissue microarray showed that LDP staining of 73.2% (30/41) of breast cancer tissues was positive, whereas that of 48.3% (15/31) of the adjacent normal breast specimens was positive. The difference between the tumor and normal samples was significant (Chi2 = 4.63, P < 0.05). LDP immunoreactivity in breast cancer correlated significantly with the overexpression of VEGF and HER2 (P < 0.001 and < 0.01, r = 0.389 and 0.287, respectively). Determined with confocal immunofluorescent analysis, LDP showed the binding capability to mammary carcinoma MCF-7 cells. It is demonstrated that LDP can bind to human breast cancer tissues and there is significant difference between the breast cancer tissues and the corresponding normal tissues. Notably, the binding reactivity shows positive correlation with the expression of VEGF and HER2 in breast carcinoma tissues. The results imply that LDP may have a potential use as targeting drug carrier in the research and development of new anticancer therapeutics. This study may provide reference for drug combination of LDM and other therapeutic agents.
Aminoglycosides ; metabolism ; Antibiotics, Antineoplastic ; metabolism ; Apoproteins ; metabolism ; Breast Neoplasms ; metabolism ; pathology ; Cell Line, Tumor ; Enediynes ; metabolism ; Female ; Humans ; Protein Binding ; Receptor, ErbB-2 ; metabolism ; Tissue Array Analysis ; methods ; Vascular Endothelial Growth Factor A ; metabolism

Objective To understand the effect of hyaluronic acid (HA) on the proliferation and apoptosis of chondrocytes cultured in vitro with Kashin-Beck disease(KBD) to provide the experimental evidences for treating KBD diseases with HA. Methods The articular cartilage samples collected from KBD patients were selected according to Diagnosis for Kaschin-Beck Disease(GB 16003-1995). And the normal cartilage samples were collected from victims of incidence (control). Chandrocytes were separated and cultured in vitro. Then varying dosages of HA were administered to chondrocytes and individed into 0,100,500 mg/L group, according to HA doages. The effect of HA on the proliferation and apoptosis of chondrocytes cultured/n vitro both KBD and the controls were investigated by methyl thiazolyl tetrazolium(MTT), Annexin V/PI staining on 2~(nd), 4~(th), 6~(th) day. Results In the control group, 500 mg/L group(0.140 ± 0.049) promoted chondrocyte proliferation significantly than 0 mg/L group (0.116 ± 0.021 ) at the 4~(th) day(P < 0.05), similar phenomenon was observed in KBD group in the 6~(th) day between 500 and 0 mg/L group(0.179 ± 0.081,0.128 ± 0.017, P< 0.05). In the KBD group, compared with 0 mg/L (12.860 ± 2.159), both 100 and 500 mg/L( 10.458 ± 1.143,7.877 ± 1.346) inhibited chondrocyte apoptosis rate (P < 0.05). In control, apoptosis rate of 500 mg/L group(4.045 ± 1.204) descreased compared with 0 mg/L group (7.128 ± 1.244, P < 0.05). Conclusion HA can promote the proliferation and inhibit the apoptosis of KBD chondrocytes cultured in vitro, and 500 mg/L HA play more effective role than that of 100 mg/L in promoting proliferation and inhibiting poptosis.

OBJECTIVETo study the effects of the change in transient receptor potential vanilloid 1 (TRPV1) channel activity on the degree of airway inflammation in asthmatic mice.

METHODSBALB/c mice were randomly divided into control, asthma, capsaicin (TRPV1 agonist), capsazepine (TRPV1 antagonist), and dexamethasone groups. The asthmatic mouse model was established by intraperitoneal injection of mixed ovalbumin-aluminium hydroxide solution and ultrasonic atomization with OVA for sensitization and challenge. The capsaicin, capsazepine, and dexamethasone groups were given intraperitoneal injection of capsaicin (30 μg/kg), capsazepine (10 μmol/kg), and dexamethasone (2 mg/kg) respectively, at 30 minutes before challenge. Hematoxylin and eosin staining was used to observe the degree of pulmonary inflammation. ELISA was used to measure the content of interleukin-8 (IL-8) and interleukin-13 (IL-13) in bronchoalveolar lavage fluid (BALF). Real-Time PCR was used to measure the relative content of TRPV1 mRNA in lung tissue.

RESULTSCompared with the asthma group, the capsazepine and dexamethasone groups showed reduced pulmonary inflammation, while the capsaicin group showed aggravated pulmonary inflammation. Compared with the control group, the asthma and capsaicin groups showed increases in the content of IL-13 and IL-8 in BALF and the mRNA expression of TRPV1 in lung tissue (P<0.05). Compared with the asthma group, the capsazepine and dexamethasone groups showed reductions in the content of IL-13 and IL-8 in BALF and the mRNA expression of TRPV1 in lung tissue (P<0.05). The capsaicin group showed increases in the content of IL-13 and IL-8 in BALF (P<0.05).

CONCLUSIONSTRPV1 channel agonist and antagonist can influence the degree of airway inflammation in asthmatic mice. Dexamethasone may reduce airway inflammation through regulating TRPV1 level.

Animals ; Asthma ; etiology ; Female ; Interleukin-13 ; analysis ; Interleukin-8 ; analysis ; Lung ; pathology ; Mice ; Mice, Inbred BALB C ; RNA, Messenger ; analysis ; TRPV Cation Channels ; genetics ; physiology

[Objective] To investigate the significance of liver biopsy in differential diagnosis and prognosis of congenital biliary atresia (CBA) and infant hepatitis syndrome (IHS).[Methods] Totally 77 children with congenital biliary atresia and 48 infants with hepatitis syndrome treated in Guangdong Women and Children Hospital from December 2012 to December 2016 were examined by liver biopsy and follow-up.Combined with immunohistochemistry and PAS staining,reticular fiber staining,Masson staining techniques,we make comparative analysis of both histopathological features and prognosis.[Results] The liver fibrosis grade,hepatic lobule inflammation activity staging,the degree of bile duct hyperplasia and the prognosis of CBA and IHS infants were statistically significant (P＜0.05).S2-S3-based liver fibrosis grading in infants with CBA,mainly in G2-G3 hepatic lobule inflammation staging,bile duct hyperplasia significantly;IHS infants with liver fibrosis grading as S0-S1,liver Slice inflammatory activity stage to G1-G2-based.The prognosis of infants with CBA was significantly worse than IHS,and the difference was statistically significant (P＜0.05).[Conclusion] The early liver biopsy of infants with congenital biliary atresia and infant hepatitis syndrome,combined with immunohistochemistry and PAS staining,reticular fiber staining,Masson staining techniques has important clinical significance to the differential diagnosis and prognosis of both.

OBJECTIVETo investigate the effect of lidamycin (LDM) on telomerase activity in human hepatoma BEL-7402 cells under the condition of LDM inducing mitotic cell death and senescence.

METHODSChromatin condensation was detected by co-staining with Hoechst 33342 and PI. Cell multinucleation was observed by Giemsa staining and genomic DNA was separated by agarose gel electrophoresis. Fluorescent intensity of Rho123 was determined for mitochondrial membrane potential. MTT assay and SA-beta-gal staining were employed to analyze the senescence-like phenotype. The expression of proteins was analyzed by Western blot. Telomerase activity was assayed by telomerase PCR-ELISA.

RESULTSMitotic cell death occurred in LDM-treated cells characterized by unique and atypical chromatin condensation, multinucleation and increased mitochondrial membrane potential. However, no apoptotic bodies or DNA ladders were found. In addition, apoptosis-related proteins remained nearly unaltered. Senescence-like phenotype was identified by increased and elongated size of cells, growth retardation, enhanced SA-beta-gal activity and the changes of senescence-related protein expression. Telomerase activity markedly decreased (P<0.01) in LDM-treated hepatoma BEL-7402 cells.

CONCLUSIONMitotic cell death and senescence could be triggered simultaneously or sequentially after exposure of hepatoma BEL-7402 cells to LDM. The decrease in telomerase activity may play a key role in the defective mitosis and aging morphology. Further investigation of detailed mechanism is needed.

Aminoglycosides ; pharmacology ; Antibiotics, Antineoplastic ; pharmacology ; Apoptosis ; drug effects ; Azure Stains ; Benzimidazoles ; Carcinoma, Hepatocellular ; enzymology ; pathology ; Cell Nucleus ; drug effects ; metabolism ; Cellular Senescence ; drug effects ; Chromatin ; metabolism ; DNA, Neoplasm ; analysis ; Dose-Response Relationship, Drug ; Enediynes ; pharmacology ; Genome, Human ; genetics ; Humans ; Liver Neoplasms ; enzymology ; pathology ; Membrane Potential, Mitochondrial ; drug effects ; Mitosis ; drug effects ; Phenotype ; Propidium ; Telomerase ; metabolism ; Time Factors ; beta-Galactosidase ; metabolism

OBJECTIVETo establish an accurate new rat model of hyperammonemia-induced liver injury for use in studies of the molecular mechanisms underlying acute liver failure (ALF).

METHODSTwenty-six Sprague-Dawley rats were administered D-galactosamine (400 mg/kg) and endotoxin (50 mug/kg) via intraperitoneal injection to induce ALF and sacrificed at 12 h post-injection (ALF-12 group, n = 10) or 24 h post-injection (ALF-24 group, n = 16). Ten rats administered physiological saline served as the control group. In addition, 20 rats were given serial oral administrations of 10% NH4Cl solution (10 ml/kg, every 8 hrs) to establish the hyperammonemia-induced liver injury model; an additional 20 rats were prepared in parallel to serve as the ALF control group (n = 10; D-galactosamine at 800 mg/kg every 6 d for 30 days) and the physiological saline control group (n = 10). Serum samples were collected from each mouse and used to detect markers of liver function, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-fetal protein (AFP), and gamma-glutamyltransferase (GGT), as well as blood ammonia (BA) level and prothrombin time activity (PT-A). Affects on liver histology was assessed by hematoxylin and eosin staining of resected liver tissues, and on apoptosis by TUNEL assay and calculating the apoptotic index (AI).

RESULTSALF rats showed elevated levels of ALT (1202.51+/-282.00 U/L), AST (1560.14+/-298.98 U/L), and BA (165.9+/-23.6 mumol/L) as early as 6 hrs after model establishment; these levels peaked at 12 hrs after model establishment (ALT: 774.40+/-207.65 U/L; AST: 967.60+/-121.94 U/L; BA: 143.4+/-18.1 mumol/L; P less than 0.05). No significant variations were detected in the levels of AFP (except for the ALF-24 group) or GGT. Liver tissues of the ALF-12 and ALF-24 groups showed large or diffuse hemorrhagic necroses with sinusoidal congestion or spotty bleeding, as well as increased AI. Hyperammonemia-induced liver injury rats showed elevated levels of ALT and BA as early as 6 hrs after model establishment. Similar to the ALF rats, AFP and GGT were unaffected and AI increased. However, in contrast to the ALF rats, the liver tissues of the hyperammonemia-induced liver injury rats showed no signs of hepatocyte swelling, necrosis, or inflammatory cell invasion.

CONCLUSIONALF rats and hyperammonemia-induced liver injury rats have elevated BA and marked hepatocyte necrosis. Given that reducing the level of ammonemia can improve the animal's biochemistry indexes, it is likely that hyperammonemia plays a role in acute liver injury or ALF consequent to repeated injury. The pathogenic mechanisms of repeated injury may involve promotion of hepatocyte apoptosis in conjunction with inhibition of cellular regeneration.

Animals ; Disease Models, Animal ; Hyperammonemia ; complications ; Liver Failure, Acute ; etiology ; Male ; Rats ; Rats, Sprague-Dawley