Objective To investigate the com and pepper fluorine in Zhenxiong county of Yunnan province, as well as the change of com and pepper fluorine after baked by coal, clay-mixed with cual for a relatively long-term, in order to provide a scientific basis for reducing fluorine intake. Methods The endemic areas of Yile, Wufeng's Songlinwan, Tangfang and Wufeng's Wugu in Zhenxiong county, and a non-endemic area Xiaguan in Dali city were selected as study sites. Ten samples of fresh corn and pepper were collected in each region, and fluorine was determined using acid leaching/potentiometry freshly and after baking or drying for 10 days or 4 months, respectively. Results The fluorine content of local fresh corn in Xiaguan of Dali city and Yile,Wufeng's Songlinwan, Tangfang, Wufeng's Wugu in Zhenxiong county were (1.31 ± 0.13),(1.65 ± 0.64),(1.92 ±0.37), (2.32 ± 0.49), (1.98 ± 0.66)mg/kg, respectively, and there were statistically significant differences across the regions(H = 27.871, P ＜ 0.05). The fluorine content of corn samples after baking or drying for 4 months were ( 1.82 ± 0.17), (26.43 ± 12.03), (39.27 ± 8.09), ( 14.27 ± 4.37), ( 14.33 ± 1.73)mg/kg, respectively, which were significantly higher than that of the fresh com in the corresponding region(all P ＜ 0.05 ), and there were statistically significant differences across the regions(H = 42.512, P＜ 0.05). The fluorine content of the local fresh chili were (3.34 ± 1.08), (3.44 ± 0.55), (3.47 ± 0.74), (3.46 ± 0.93)mg/kg, respectively, in the 4 observed places in Xiaguan of Dali city and Yile, Wufeng's Songlinwan, Tangfang in Zhenxiong county, and there were no statistically significant differences across the regions (F = 0.052, P ＞ 0.05 ). The fluorine content of pepper samples after baking or drying for 4 months were (7.01 ± 1.64), (226.07 ± 83.69), (179.36 ± 148.37), (54.51 ± 34.67)mg/kg,respectively, which were significantly higher than that of the fresh pepper in the corresponding region(all P ＜ 0.05 ),and there were statistically significant differences across the regions(H = 28.822, P ＜ 0.05). Conclusion Corn and chili fluorine is significantly increased after baked with coal and clay-mixed with coal by farmers in Zhenxiong county, a coal- burning borne endemic fluorosis area of Yunnan province.

Child ; Child, Preschool ; Encephalitis, Viral ; diagnosis ; Female ; Humans ; Infant ; Magnetic Resonance Angiography ; Magnetic Resonance Imaging ; Male

Administration, Inhalation ; Drug Therapy, Combination ; Female ; Hernias, Diaphragmatic, Congenital ; drug therapy ; Humans ; Infant, Newborn ; Male ; Nitric Oxide ; administration & dosage ; Piperazines ; administration & dosage ; Purines ; administration & dosage ; Sildenafil Citrate ; Sulfones ; administration & dosage

OBJECTIVETo investigate the characteristics and clinical outcome of T315I mutation in Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) and chronic myeloid leukemia (CML).

METHODSThe clinical data of 118 tyrosine kinase inhibitors (TKIs) resistant Ph(+) ALL and CML cases who were detected ABL kinase domain mutation in Affiliated Tumor Hospital of Zhengzhou University from March 2014 to June 2015 were collected. Karyotypes and BCR-ABL fusion gene were analyzed respectively by R-banding, real-time quantitative polymerase chain reaction (PCR). Total RNA was extracted by TRIzol reagent and ABL kinase domain mutation was detected by direct sequencing.

RESULTSIn 23 TKIs resistant Ph(+) ALL and 95 CML cases, the rate of ABL kinase domain mutation was 60.9% (14/23) and 41.1% (39/95), respectively, and the rate of T315I mutation was respectively 34. 8% vs 5.3%, the difference was significant (χ(2)=13.586, P<0.01). The rate of mutations in chronic phase/accelerate phase /blast crisis CML patients was 38.8% (19/49), 47.1% (8/17) and 41.4% (12/29), respectively, and there was no significant difference (χ(2)=0.360, P=0.835). In Ph (+) ALL and CML patients, the median time from the beginning of TKI therapy to appearance of T315I mutation was 10 months and 19 months, the median time from the appearance of T315I to death/deadline was 2 months and 3 months, the median time of persistent hematologic response was 10 months and 16 months and the median time of overall survival (OS) was 13 months and 42 months.

CONCLUSIONT315I mutation was more easily occurred in Ph(+) ALL than CML, but two diseases are similar in the median time from the beginning of TKI therapy to appearance of T315I, the median time of persistent hematologic response and OS.

Acute Disease ; Blast Crisis ; Drug Resistance, Neoplasm ; Fusion Proteins, bcr-abl ; genetics ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; genetics ; Mutation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; Protein Kinase Inhibitors ; therapeutic use

The aim of this study was to investigate the mechanism to reverse the drug resistance of leukemia cells in tetrandrine (Tet) alone or in combination with droloxifen (Drol) by using protein chips and to lay the theoretical basis for the clinical applications. Three monoclonal antibodies against P-glycoprotein (P-gp), the multidrug resistance-associated protein (MRP1) and the breast cancer resistance protein (BCRP) were immobilized onto the agarose gel film-coated glass slides. Protein chips were prepared respectively from K562/A02 cells cultured for 12, 24 and 48 hours with Tet alone or in combination with Drol. The results showed that Tet alone or in combination with Drol could decrease only the expression of P-gp in a time-dependent manner, the effect for 48 hours as follows: Tet + Drol 82.620 +/- 3.227; Tet alone 86.440 +/- 2.906; Drol alone 87.230 +/- 2.049; control 93.670 +/- 2.748 (P < 0.05). However, down-regulation of P-gp by K562/A02 cells cultured with Tet alone or in combination with Drol began at 24 hours (Tet + Drol 85.270 +/- 3.095; control 93.670 +/- 2.748, P < 0.05). The results were coincident with that of FCM. It is concluded that Tet and Drol can downregulate the expression of P-gp in the time-dependent way. There is a significant difference between Tet alone and Tet combined with Drol at 24 hours (P < 0.05). The expression of MRP1 and BCRP are not closely correlated with the reversal mechanism of Tet and Drol, and which may be involved in the mechanism of this combination to reverse multidrug resistance in leukemia.
ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters ; biosynthesis ; ATP-Binding Cassette, Sub-Family B, Member 1 ; biosynthesis ; Antineoplastic Agents ; pharmacology ; Benzylisoquinolines ; pharmacology ; Drug Resistance, Multiple ; Drug Resistance, Neoplasm ; drug effects ; Drug Synergism ; Humans ; K562 Cells ; Leukemia ; metabolism ; pathology ; Multidrug Resistance-Associated Proteins ; biosynthesis ; Neoplasm Proteins ; biosynthesis ; Protein Array Analysis ; Tamoxifen ; analogs & derivatives ; pharmacology

Objective: To investigate the molecular-cytogenetic characterization and impact on tyrosine kinase inhibitors (TKIs) therapy in chronic phase of chronic myeloid leukemia (CML-CP) patients with variant Ph chromosome (vPh). Methods: The clinical data of 32 patients with vPh chromosomes were collected and compared with 703 patients with typical Ph chromosome in newly diagnosed CML-CP who were on first-line imatinib (IM) and with BCR-ABL transcript of P210. Results: There was no significant difference in demographic and hematological characteristics between vPh and classic Ph patients. 3(9.4%) of the 32 vPh cases were simple variant translocations. Among the remaining 29 cases with complex variant translocations, 28 cases (87.5%) involved 3 chromosomes, and only 1 (3.1%) involved 4 chromosomes. Except for 8, 15, 18, X, and Y chromosomes, the other chromosomes were involved. The frequency of chromosome 12q(15.5%) and 1p (12.1%) were higher involved. The most common FISH signal pattern was 2G2R1Y (74.1%), followed by 1G1R2F (14.8%), 2G1R1Y (3.7%), 1G2R1Y (3.7%), 1G1R1Y (3.7%). The comparison of complete cytogenetic response (CCyR) (P=0.269), major molecular response (MMR) (P=0.391) were carried out between simple and complex mechanisms, without difference. Compared with the classic Ph, the patients with vPh had higher IM primary resistance rate (χ²=3.978, P=0.046), especially primary hematological resistance (χ²=7.870, P=0.005), but the difference of CCyR (χ²=0.192, P=0.661), MMR (χ²=0.822, P=0.365), EFS (χ²=0.509, P=0.476), OS (χ²=3.485, P=0.062) were not statistically significant, and multivariate analysis showed that the presence of vPh did not affect OS (RR=0.692, 95%CI 0.393-1.765, P=0.658)、EFS (RR=0.893, 95%CI 0.347-2.132, P=0.126) and PFS (RR=1.176, 95%CI 0.643-2.682, P=0.703). Conclusion: CML-CP patients with vPh and classic Ph had similar demographic and hematological characteristics. Except for 22q11, 9q34, the frequency of chromosome 12q and 1p were higher involved. The most common FISH signal pattern was 2G2R1Y, and different mechanisms had no impact on TKIs therapy. Compared with cases with classic Ph chromosomes, the patients with vPh chromosomes had higher risk of IM primary resistance, especially primary hematological resistance, which can obtain deeper molecular response quickly after changing to second-generation TKIs and didn't affect long-term outcomes and OS.
Cytogenetics ; Fusion Proteins, bcr-abl ; Humans ; Imatinib Mesylate ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Philadelphia Chromosome ; Protein Kinase Inhibitors/therapeutic use* ; Protein-Tyrosine Kinases

OBJECTIVETo search differentially expressed proteins in serum of patients with Crohn disease.

METHODSSerum protein samples from 4 patients with Crohn disease and 8 healthy adults were recruited cross-labeled with variant CyDye, and then followed by two-dimensional differential in-gel electrophoresis (2-D DIGE), image analysis, and identified by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS).

RESULTSThe 2-D electrophoresis results were compared between the Crohn disease patients and the healthy adults. The spot 1058 expression in serum of Crohn disease patients increased by 1.68 folds as compared with healthy adults (P<0.05). The protein was identified as haptoglobin by mass spectrometry.

CONCLUSIONUp-regulating expression of haptoglobin in serum of Crohn disease patients may play a role in disequilibrium of immunity system.

Adult ; Blood Proteins ; metabolism ; Case-Control Studies ; Crohn Disease ; blood ; Electrophoresis, Gel, Two-Dimensional ; Haptoglobins ; metabolism ; Humans ; Proteomics ; methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

OBJECTIVETo assess the prevalence of occult HBV infection in HIV-infected patients inacquired immune deficiency syndrome area.

METHODSSerum samples were obtained from 97 HIV-infected patients who transmitted by paid blood donation. ELISA was used to detect HBV erologic markers (HBsAg, Anti-HBs, HBeAg, anti-HBe and anti-HBc) and HCV antibody. Flow Cytometry were used to detect CD4+ T cell count. Nested PCR was used to amplify surface protein region of HBV DNA.

RESULTSNinety two patients were HBsAg negative in the 97 HIV-infected patients (94.85%). Twenty seven patients were co-infected with occult hepatitis B virus infection in the 92 HBsAg negative patients (29.35%). Seventy three patients were co-infected with HCV in the 92 HBsAg negative patients(79.35%). CD4 cell count of subjects with occult HBV infection were significantly lower (212.11 +/- 133.1 cells/mm3 versus 318.9 +/- 172.2 cells/mm3, respectively, P < 0.01). A significantly higher prevalence of isolated anti-HBc was observed in HIV-infected subjects co-infectioned with occult HBV infection [62.96% (13 of 27) versus 18.46% (15 of 65), P < 0.01]. No statistical significant association could be established between the age, sex and whether co-infected with HCV.

CONCLUSIONIt is found that occult HBV infection did occurs in HIV-infected patients. Individuals co-infected with HIV and occult HBV infection are more likely to have isolated anti-HBc than subjects with HIV alone. Co-infection with HIV and occult HBV is more likely to occue in subjects with lower CD4.

Acquired Immunodeficiency Syndrome ; immunology ; virology ; Adult ; Cross-Sectional Studies ; Female ; HIV ; immunology ; isolation & purification ; HIV Infections ; immunology ; virology ; Hepatitis B ; immunology ; virology ; Hepatitis B virus ; immunology ; isolation & purification ; Humans ; Male

OBJECTIVETo evaluate the use of protein array chips in detection of multidrug-resistance proteins.

METHODSHuman erythroleukemic cell line K562 and its doxorubicin-resistant counterpart K562/A02 were used in the study. Monoclonal antibodies against P-glycoprotein (P-gP), multidrug resistance-associated protein (MRP1) and breast cancer resistance protein (BCRP) were immobilized onto agarose film-coated glass. The antibody-cell binding was assessed by capturing K562 and K562/A02 cells. The protein array was observed under a microscope and the image was captured with a CCD camera. The expression levels of the three proteins were also measured by flow cytometry (FCM).

RESULTSThe expression of P-gP and BCRP in K562 was very low. However, MRP1 expression was high. P-gP and MRP1 were highly expressed in K562/A02, while the expression of BCRP was low. FCM results showed that the expression rate of P-gP, MRP1 and BCRP in K562 cells was 5.98% +/- 2.19%, 95.80% +/- 3.98%, 1.03% +/- 0.45%, respectively, while that in K562/A02 cells was 92.67% +/- 1.80%, 97.18% +/- 1.02%, 3.98% +/- 0.37%, respectively. The results of protein array method are consistent with those of FCM (P > 0.05).

CONCLUSIONIt is feasible to develop a new protein array technique and to provide a novel method for multi-drug resistant cell detection, with a high throughput, high specificity, simple procedure and low cost.

ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters ; analysis ; ATP-Binding Cassette, Sub-Family B, Member 1 ; analysis ; Drug Resistance, Multiple ; genetics ; Drug Resistance, Neoplasm ; genetics ; Humans ; K562 Cells ; Multidrug Resistance-Associated Proteins ; analysis ; Neoplasm Proteins ; analysis ; Protein Array Analysis

BACKGROUNDHuman epididymis secretory protein 4 (HE4) has been proved to be a promising novel biomarker for the detection of epithelial ovarian carcinomas. Compared with CA125, HE4 assay demonstrated an improved ability to discriminate between pelvic mass with malignant and benign disease. Though it is well known that HE4 is overexpressed in ovarian cancer, however, the role of HE4 in the carcinogenesis and progression of ovarian cancer remains unkown.

METHODSIn this study, we explored the role of HE4 in the carcinogenesis and progression of ovarian cancer. We screened nine ovarian cancer cell lines for HE4 expression, and using RNA interference (RNAi), we silenced HE4 gene expression in CaoV3 and SKOV3.ip1 ovarian cancer cell lines. We assessed the effect of HE4 gene silencing on the transformed phenotype by examining the cell cycle, apoptosis, proliferation and transwell migration/invasion in vitro.

RESULTSHE4 gene silencing induces G0/G1 arrest and blocks the progression from the G1 to S phase in CaoV3 and SKOV3.ip1 cells. HE4 knockdown also inhibited cell proliferation, migration and invasion in SKOV3.ip1 cells in vitro.

CONCLUSIONHE4 may be involved in the regulation of the cell cycle and promote ovarian cancer migration and invasion.

Biomarkers, Tumor ; analysis ; Cell Line, Tumor ; Disease Progression ; Epididymal Secretory Proteins ; analysis ; genetics ; physiology ; Female ; Gene Silencing ; physiology ; Humans ; Ovarian Neoplasms ; pathology ; RNA Interference