Objective To determine the protein expression of P14ARF,MDM2 and mutant type P53 (P53mt) in skin specimens of coal-burning-type of endemic arseniasis patients and to reveal the molecular mechanism of the disease.Methods Sixty skin specimens from 60 endemic arseniasis patients including 35 of skin lesions patients,19 of precancerous lesion and 6 of skin cancer and 9 normal skin specimens from non-cancer patients were studied.Expression of P14~,MDM2 and P53mt was evaluated by immunohistochemistry using corresponding monoclonal antibodies.Results There was significant difference in the positive rates of P14ARF,MDM2 and P53mt among the 4 groups(x2 =9.39,6.21,20.64,all P ＜ 0.05).The positive rates of P14ARF in precancerous lesion and skin cancer specimens were 46.1％ (6/19) and 33.3％ (2/6),respectively,which were significantly lower than that of the normal skin specimens [88.9％(8/9),all P ＜ 0.05].Decreased expression of P14ARF was correlated with the development of dermopathy (P ＜ 0.05).The positive rates of MDM2 and P53mt in skin lesions,precancerous lesion and skin cancer specimens were 54.2％ ( 19/35 ),63.2％ (10/19),66.7％ (4/6) and 25.7％(9/35),73.7％(14/19),83.3％(5/6),respectively,which were significantly higher than those of the control (0,0,all P＜ 0.05).The expression of MDM2 and P53mt increased with the development of dermopathy(all P ＜ 0.05).Conclusions P53mt protein in skin tissue of coal-burning-type of endemic arseniasis patients is over expressed.Abnormal expression of P14ARF and MDM2 may be one of the reasons lead to abnormal cell cycle control disorders and may play a role in the development of endemic arseniasis.

Objective To investigate the levels of serum vascular endothelial growth factor(VEGF) and basic fibroblast growth factor(bFGF) in patients with non-small cell lung cancer(NSCLC) and relationships with c1inicopatho1ogica1 characteristics and their clinical significance. Methods The concentrations of serum VEGF and bFGF were detected by enzyme-linked immunosorbent assay(ELISA) in 40 patients with NSCLC before and after chemotherapy. Results The level of serum VEGF in patients with Ⅳ stage NSCLC was significantly higher than that of Ⅲ stage(P

Objective To investigate the state of drinking water defluorination project in Dagang district and study urinary fluoride levels and detect dental fluorosis of children aged 8 to 12, and to provide scientific basis for prevention and control of fluorosis. Methods Five defluorination projects in rural streets (towns) with highfluoride water and 2 urban water supply projects were choosen to investigate the running status in Dagang district Tianjin in 2009. Five rural and 2 urban schools were choosen to select 100 children aged 8 to 12 (for gender, age matched) in each primary school to study urinary fluoride levels and detection of dental fluorosis. Results A total of 66 defluorination projects in 73 villages were surveyed, among which 61 projects actually worked normally with using rate 92.4%(61/66). Water qualification of all projects could not be ensured due to direct project managers'lack of necessary expertise. In 2009, water qualification rate were 39.3%(24/61 )among the project normally used,with highlighted problem of biological pollution. A total of 490 children aged 8 - 12 in 5 rural towns were surveyed,dental fluorosis rate were 90%(441/490), and dental fluorosis index were 1.82. A total of 207 children aged 8 - 12in 2 urban areas were surveyed, the detection rate of dental fluorosis was 49.8%(103/207), and dental fluorosis index were 0.86. The urinary fluoride level of 230 children aged 8 - 12 in the 5 villages were surveyed. The Range of geometric mean of urinary fluoride were 1.82 - 2.70 mg/L. The urinary fluoride of 102 children aged 8 - 12 in the 2 urban area were surveyed. The Range of geometric mean of urinary fluoride were 1.53 - 1.72 mg/L. Conclusions There was phenomenon of high coverage, low utilization rate and less water consumption in the villages of Dagang district, Tianjin drinking water defluoridation projects, thus the health effects of the projects was minimum.Significant health effects is found in the defluorination projects in the urban areas with high coverage and high utilization rate. Studying new water improvment methods and new forms of water supply system is urgent for solving the problems met in the ineffective water defluorination project.

This study was aimed to investigate the effects of decitabine (DAC) on proliferation and apoptosis of leukemia NB4 and K562 cells. The proliferation inhibition of DAC on NB4 and K562 cells was detected by Trypan blue staining. After treatment of DAC at different concentrations, the changes of cell cycle and CD11b expression was determined by flow cytometry. The cell morphological changes were observed by Wright's staining. The DNA ladder was used to detect cell apoptosis. The results indicated that DAC significantly inhibited the proliferation of NB4 and K562 cells in dose-and time-dependent manner. The median inhibitory concentration (IC50) of DAC-treated NB4 and K562 cells for 72 h was 0.113 µmol/L and 0.138 µmol/L, respectively. After treating these two cell lines with DAC at different concentration for 72 h, the cell ratio in G0/G1 phase significantly increased, while the cell ratio in S phase obviously decreased in 0.15 µmol/L DAC group (P < 0.05). The expression levels of myeloid differentiation antigen CD11b of both cell lines significantly increased in contrast to the control group (P < 0.05). The cell morphology detected by Wright's staining displayed partial differentiation and apoptosis after treating NB4 and K562 cells with DAC for 48 h. Typical apoptotic DNA ladder was observed in 0.15 µmol/L DAC group at 48 h. It is concluded that DAC can inhibit NB4 and K562 cell proliferation, induce cell differentiation and apoptosis, but more obviously for NB4 cells.
Apoptosis ; drug effects ; Azacitidine ; analogs & derivatives ; pharmacology ; Cell Differentiation ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; K562 Cells

OBJECTIVETo analyze the differential proteomics in human umbilical cord mesenchymal stem cells (MSC) induced by chemical hypoxia-mimetic agent cobalt chloride (CoCl(2)) by two-dimensional gel electrophoresis (2-DE) and mass-spectrometry.

METHODS2-DE was performed to separate proteins from treated and untreated human umbilical cord MSC with CoCl(2). 2-DE images were analyzed by ImageMaster 2D Platinum software 6.0. The differential expressed proteins was identified by MALDI-TOF-MS. The differential proteins were classified based on their functions.

RESULTS2-DE reference patterns of CoCl(2) treated human umbilical cord MSC were established. A total of twenty-six differential proteins were identified, of them eleven proteins were up-regulated and fifteen down-regulated. Their biological functions involved in carbohydrate metabolism, protein metabolism and modification, lipid metabolism, coenzyme and prosthetic group metabolism, cell cycle, immunity and defense, cell structure and motility, signal transduction, protein targeting and localization, neuronal activities, muscle contraction, etc. Peroxiredoxin1 (Prdx) was down-regulated, whereas alpha-enolase (ENO1) and vesicle amine transport protein 1 homolog (VAT1) up-regulated.

CONCLUSIONThe effects of hypoxia on human umbilical cord MSC were participated by multiple proteins and involved in multiple functional pathways.

Cobalt ; pharmacology ; Humans ; Mesenchymal Stromal Cells ; drug effects ; metabolism ; Proteome ; analysis ; Proteomics ; Umbilical Cord ; cytology ; drug effects

The purpose of the present study was to investigate the effect of melatonin (MT) on the abnormal reactivity of thoracic aorta and pulmonary artery induced by lipopolysaccharide (LPS) in rats. Sprague-Dawley rats were divided into four groups randomly: (1) Vehicle group; (2) LPS group: LPS (4 mg/kg, i.p.); (3) LPS+MT group: MT (5 mg/ml, i.p.) was given 30 min before LPS and 60 min after LPS (4 mg/kg ,i.p); (4) MT group: received two doses of MT, 90 min after the first injection of MT another dose of MT was given. Six hours after LPS injection,the rats were killed and both thoracic aortic rings (TARs) and pulmonary artery rings (PARs)were prepared. The reactivity of TARs and PARs in the four subgroups was tested separately. The contraction response to phenylephrine (PE) and the endothelium-dependent relaxation response (EDRR) to ACh were observed with the isolated artery ring technique. Concentration-response curves were generated with ACh or PE (1 x 10(-8) - 1 x 10(-5) mol/L). Superoxide dismutes (SOD) activity and the content of malondialhyde (MDA) in artery tissues were detected. For TARs, LPS significantly reduced the contraction response to PE compared with the vehicle group (P<0.01) and the curve of cumulative dose responses to PE in the LPS group shifted downward. Although EDRR to ACh in the LPS group had the tendency to decrease but still showed no significant difference compared with the vehicle group (P>0.05). For PARs, EDRR to ACh was depressed significantly in the LPS group (P<0.01), while no effect on contraction response to PE in the LPS group was observed, compared with the vehicle group (P> 0.05). Compared with the LPS group, TARs in the LPS+MT group exhibited an increased contraction response to PE, but were still lower than that in the vehicle group. Similarly, EDRR to ACh of PARs in the LPS+MT group was improved significantly and there was no difference between the LPS+MT group and the vehicle group. The vascular reactivity was unaffected in MT group compared with the vehicle group in both TARs and PARs. SOD activity in the LPS +MT group increased significantly and the content of MDA decreased markedly compared with the LPS group. These results suggest that MT may improve the vascular reactivity in endotoxemia rats due to its antioxidant properties.
Animals ; Aorta, Thoracic ; physiopathology ; Endotoxemia ; chemically induced ; physiopathology ; Free Radical Scavengers ; pharmacology ; Lipopolysaccharides ; Male ; Melatonin ; pharmacology ; Pulmonary Artery ; physiopathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; Vasoconstriction ; drug effects ; Vasodilation ; drug effects

OBJECTIVETo evaluate the efficacy and safety of antifungal prophylaxis of itraconazole in patients with acute myeloid leukemia (AML) to probe the relationship of the antifungal effect and the adverse events with serum concentration.

METHODSFrom April 2009 to May 2011, a total of 310 courses from 112 patients referred to our institute were enrolled in this study; of them, 297 courses were eligible for analysis. Eligible cases were randomized into oral group and injection/oral group according to different chemotherapy of induction and consolidation. Blood samples were collected at different time points for measurements of serum itraconazole levels. The morbidity of IFI and the adverse events were analyzed.

RESULTSThe morbidities of IFI in injection/oral and oral groups were 10.1% and 20.9%, respectively (P=0.010). 7 and 9 cases in injection/oral and oral groups, respectively were withdrawn from the study because of adverse events, and the difference between these two groups was of no significance. Serum itraconazole levels of injection/oral and oral groups were 672(299-1097) μg/L and 534(210-936) μg/L, respectively (P<0.01).

CONCLUSIONAntifungal prophylaxis with itraconazole in AML patients was effective and safe. Prophylactic effect with injection/oral itraconazole was superior to oral itraconazole solution; moreover, prophylactic effect of itraconazole was highly correlated with its serum level.

Adolescent ; Adult ; Antibiotic Prophylaxis ; Antifungal Agents ; therapeutic use ; Female ; Humans ; Itraconazole ; blood ; therapeutic use ; Leukemia, Myeloid, Acute ; drug therapy ; microbiology ; Male ; Middle Aged ; Mycoses ; etiology ; prevention & control ; Young Adult

OBJECTIVETo study the expression changes of neuroglobin in rats with the model of diffuse traumatic brain injury and explore the relationship between the neuroglobin and neuron apoptosis in traumatic brain injury.

METHODSThe diffuse traumatic brain injury of rats was induced by the Marmarou's 'weight-drop' device. And the immunohistochemical technique was used to detect the expression changes of neuroglobin and neuron apoptosis in rat brain at different time points post-injury.

RESULTSThe expression of neuroglobin increased twice and reached peaks at 2 hours and 72 hours post-injury respectively. And the increased expression of neuroglobin from 30 minutes to 1 hour post-injury and from 48 hours to 72 hours post-injury accompanied with the decreased expression ratio of Bax to Bcl-2.

CONCLUSIONThe increased expression of neuroglobin in traumatic brain injury informed us that neuroglobin had anti-apoptosis action in post-injury neuron. It could protect the neuron from traumatic stress and secondary ischemia and hypoxia insults during ultra-early and acute stages.

Animals ; Apoptosis ; physiology ; Brain ; metabolism ; pathology ; Brain Injuries ; metabolism ; pathology ; Globins ; metabolism ; Male ; Nerve Tissue Proteins ; metabolism ; Neurons ; pathology ; Random Allocation ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the efficacy, median time to progression (TTP), quality of life and toxicity in the patients with advanced non-small cell lung cancer (NSCLC), treated with thalidomide plus vinorelbine and cisplatin (NP) or NP alone.

METHODSSixty six patients with advanced NSCLC were divided randomly into two groups, the trial and control groups. The trial group was treated with vinorelbine 25 approximately 30 mg/m(2) i.v. on D1 and D8, cisplatin 70 approximately 80 mg/m(2) i.v. on D1 (NP regimen), and thalidomide 200 mg orally and daily from D1. The control group received vinorelbine and cisplatin as above described.

RESULTSOf 66 assessable patients, the overall response rate was 51.5% in the trial group and 36.4% in the control group (P = 0.22). The median TTP was 6.0 months for the trial group, and 3.6 months for the control group (P < 0.001). The score of quality of life in trial group was higher than that in the control group, but no significant difference was observed between the two groups (P > 0.05). There were no significant differences in toxicities between the two groups (P > 0.05).

CONCLUSIONNP regimen combined with thalidomide can significantly prolong the median time to tumor progression in patients with advanced NSCLC. Thalidomide may have a synergic activity with NP regimen without increased toxicities.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; pathology ; Cisplatin ; administration & dosage ; adverse effects ; Disease Progression ; Drug Synergism ; Feeding and Eating Disorders ; chemically induced ; Female ; Follow-Up Studies ; Humans ; Leukopenia ; chemically induced ; Lung Neoplasms ; drug therapy ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Quality of Life ; Remission Induction ; Thalidomide ; administration & dosage ; adverse effects ; Thrombocytopenia ; chemically induced ; Vinblastine ; administration & dosage ; adverse effects ; analogs & derivatives ; Vomiting ; chemically induced

OBJECTIVETo study the clinicopathologic features of myeloid sarcoma and to evaluate the role of immunohistochemical study in diagnosis of this entity.

METHODSEighty-two cases of myeloid sarcoma were retrieved from the archives of Department of Pathology, West China Hospital of Sichuan University during the period from January, 1990 to February, 2005. The morphologic features were reviewed and classified according to the 2001 WHO classification for hematopoietic and lymphoid tissue tumors. Immunohistochemical study using a panel of 11 antibodies was performed on 73 cases. The survival data were collected and analyzed by SPSS 10.0.

RESULTSThe median age of patients was 35.5 years. The male-to-female ratio was 1.4:1. The sites of occurrence included lymph node (43.1%), skin (16.7%), nose (7.8%), soft tissue (7.8%) and bone (6.9%). Fifty-one cases (62.2%) represented myeloid sarcoma associated with an underlying myeloproliferative disorder and 25 cases (30.5%) represented solitary myeloid sarcoma. As for the morphology, 79 cases (96.3%) were granulocytic sarcoma, including 41 cases (51.9%) blastic type, 25 cases (31.6%) immature type and 13 cases (16.5%) differentiated type. The other 3 cases (3.7%) were monoblastic sarcoma. Immature eosinophils were found in 51 cases (64.6%) of granulocytic sarcoma, among which 13 cases (31.7%) were of blastic type. Immunohistochemical study showed that 95.9% cases (70/73) were positive for myeloperoxidase, 95.5% (63/66) for lysozyme, 95.2% (60/63) for CD68 (KP1), 90.8% (59/65) for leukocyte common antigen, 85.7% (54/63) for CD43, 77.8% (49/63) for CD117, 58.7% (37/63) for CD99, 54.0% (34/63) for CD15, 22.2% (14/63) for CD34, and 4.7% (3/64) for CD68 (PG-M1). Proliferation index, as demonstrated by Ki-67 positivity, was 0.49+/-0.22. Follow-up data was obtained in 59 of the 82 patients. The two- and five-year survival rates were 36.1% and 17.3% respectively. No significant prognostic factors were found in the survival analysis.

CONCLUSIONSMyeloid sarcoma may precede, develop in a background of myeloproliferative disorder or even after remission of the disease. The presence of immature eosinophils is an important morphologic clue and immunohistochemical study plays an essential role in arriving at a correct diagnosis. Immunopositivity for myeloperoxidase is specific for granulocytic differentiation, while CD68 (PG-M1)-positivity suggests monocytic differentiation. Detailed clinicopathologic correlation is also helpful.

12E7 Antigen ; Adolescent ; Adult ; Aged ; Antigens, CD ; metabolism ; Antigens, CD34 ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Cell Adhesion Molecules ; metabolism ; Child ; Child, Preschool ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Ki-67 Antigen ; metabolism ; Leukosialin ; metabolism ; Lewis X Antigen ; metabolism ; Male ; Middle Aged ; Peroxidase ; metabolism ; Proto-Oncogene Proteins c-kit ; metabolism ; Sarcoma, Myeloid ; classification ; metabolism ; pathology ; Young Adult