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.

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

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

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

Objective To observe the clinical features,characteristics and outcomes of chromosomal abnormalities in Philadelphia negative cells (Ph-CA) of chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitor (TKI),and provide the evidence for clinical treatment.Methods We collected and analyzed the clinical and laboratory data of 8 CML patients treated in the affiliated Tumor Hospital of Zhengzhou University from September 2011 to July 2015 and Ph-CA occurred after TKI therapy.Karyotypes and BCR-ABL fusion genes were analyzed by R-banding and real-time quantitative polymerase chain reaction (RT-PCR),respectively.Results 6 cases were male and 2 cases were female,with a median age of 51 (31-75) years old.6 patients had low Sokal risk scores and 2 had intermediate scores.4 cases of Ph-CA occurred with imatinib,1 case with dasatinib and 3 cases with nilotinib.The median duration of Ph-CA appearance was 12.0 (1.7-34.5)months since taking TKI.Chromosomal abnormality +8 was the most common type in Ph-CA,which accounted for 50.0％,followed by-7 (25.0％).When found Ph CA,all patients had complete hematologic response (CHR),but none got main molecular response (MMR).The Ph-CA had gone in 7 cases at the end of follow-up and the median duration was 6.2 (2.5-31.5) months.After Ph-CA disappeared,1 patient obtained MMR and 2 cases achieved complete molecular response (CMR),but Ph+ clone recurred in 1 case.Conclusion Ph CA can be found in CML patients treated with imatinib,dasatinib and nilotinib,and +8 is the most common Ph-CA.So detection of karyotype is significant during treatment.Although most Ph CA can disappear,-7/7q-or other complex karyotypes should be monitored closely.

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

Objective To analyze the etiology of 628 patients with refractory hypertension and to observe the disease distribution with respect to gender and different age groups. Methods In this study,clinical data of 628 refractory hypertensives who hospitalized in our hospital from September 1997 to December 2005 were retrospectively analyzed. Results (1) There were 80.1% (503/628) patients with essential hypertension, 18. 9% (119/628) with secondary hypertension (SH) while diagnosis was not clear in 1.0% (6/628) patients. Renovascular hypertension (33.6%) and obstructive sleep apnea syndrome (23.5%) were the major causes of SH. The highest prevalence rate of endocrine hypertension was primary aldosteronism (13.5%). (2) There were significantly more male patients than female patients with essential hypertension, SH, renal hypertension, obstructive sleep apnea syndrome, rimary aldosteronism while the incidence of pheochromocytoma in female was significantly higher than that in male patients (all P < 0.05).The incidence of renovascular hypertension was similar between male and female patients. (3) SH occurred more often in young patients (33.1%) than in aged patients (13.8%, P < 0.05). Conclusion Our data from this patient cohort showed that SH, especially renovascular hypertension and obstructive sleep apnea syndrome are major causes for refractory hypertension in young patients and primary aldosteromsm was the commonest reason of endocrine hypertension in youth and middle-aged patients with refractory hypertension.

OBJECTIVETo found new interface of human hepatocyte/poly propylene with good cytocompatibility for made polypropylene hollow fibers bioreactor of bioartificial liver in future.

METHODSUsing the macromolecular hydroperoxide groups on the polypropylene membrane surface as initiators, acrylamides were polymerized on the polypropylene membranes, under induction by both UV irradiation and Fe2+ reduction. Growth characteristics of human hepatocyte L-02 were detected when it was cultured on polystyrene, polypropylene and modified polypropylene membrane surface.

RESULTSWater contact angle measurement of the polypropylene and the modified polypropylene membranes decreased from (72 +/- 5) degrees to (30 +/- 4) degrees , which indicated that the hydrophilicity of the membrane was improved obviously after the grafting modification. Human hepatocyte L-02 could not adhere and spread on modified polypropylene membrane surface, and grown in spheroidal aggregate with higher density and higher proliferation ratio measured by MTT method.

CONCLUSIONSAcrylamide polymerized on the polypropylene membranes is a good method which not only improved human hepatocytes cytocompatibility but also found a new simple culture method with spheroidal aggregate culture of human hepatocyte.

Cell Culture Techniques ; methods ; Cell Division ; Cells, Cultured ; Hepatocytes ; cytology ; Humans ; Liver, Artificial ; Membranes, Artificial ; Polypropylenes ; chemistry ; Surface Properties ; Tissue Engineering ; methods

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