In our previous work, we found that trivalent dimethylarsinous acid (DMA(III)) have high affinity binding to cysteine residue 13 of rat hemoglobin. However, it is still unknown why arsenic intermediate metabolite DMA(III) has high binding affinity for Cysl3 but not for other cysteine residues 93, 140, 111 and 125. In order to better understand the molecular mechanism of DMA(III) with rat hemoglobin, we have done current study. So, SD rats were divided into control and arsenic-treated groups randomly. Arsenic species in lysate of red blood cells were analyzed by HPLC-ICP-MS, and then determined by a hybrid quadrupole TOF MS. In addition, trivalent DMA(III) binds to different cysteine residues in rat hemoglobin alpha and beta chains were also simulated by Molecular Docking. Only Cys13 in alpha chain is able to bind to DMA(III) from the experiment results. Cys13 of alpha chain in rat hemoglobin is a specific binding site for DMA(III), and we found that amino acids compose pockets structure and surround Cys13 (but not other cysteine residues), make DMA(III) much easy to bind cysteine 13. Taken together, the DMA(III) specific binding to Cys13 is related to spatial structure of Cys13.
Animals ; Arsenic ; metabolism ; Binding Sites ; Cacodylic Acid ; analogs & derivatives ; chemistry ; Chromatography, High Pressure Liquid ; Cysteine ; metabolism ; Hemoglobins ; metabolism ; Mass Spectrometry ; Peptide Fragments ; metabolism ; Rats

Objective To study the correlation between interrupter technique to measure airway resistance and routine pulmonary function(Raw).Methods Using Dyn′R spirometer measure Raw and FVC,PEF,MEF_ 75,MEF_ 25,MEF_ 25～75,and calculate correlation coefficient.Results There was a negative correlation between Raw and FVC, PEF, MEF_ 75,MEF_ 25,MEF_ 25～75(r

Animals ; Animals, Newborn ; Cyclic AMP Response Element-Binding Protein ; analysis ; Hippocampus ; blood supply ; chemistry ; pathology ; Hypoxia-Ischemia, Brain ; physiopathology ; Immunohistochemistry ; Proto-Oncogene Proteins c-fos ; analysis ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; physiopathology ; Time Factors

Iron is an essential element for cell growing including tumor cells. This study was purposed to explore the effect of desferrioxamine (DFO) on cell line K562/A02 and its mechanism. K562/A02 cells were cultured with different concentrations of DFO. The inhibitory effects of adriamycin (ADM) used alone or combined with DFO on the proliferation of K562/A02 was evaluated by MTT assay. The apoptosis rate of K562/A02 cells after treatment with 0, 12.5, 25 and 50 µmol/L DFO alone or in combination with 1 mg/L ADM were analyzed by flow cytometry. ADM accumulation in K562/A02 cells after treatment with different concentrations of 0, 12.5, 25 and 50 µmol/L DFO were also analyzed by flow cytometry. The levels of BAX/BCL-2 and MDR1 mRNA were determined by RT-PCR, and then the protein level of P-glycoprotein (P-gp) was detected by Western blot. The results showed that the IC(50) of ADM for K562 and K562/A02 cells were (1.46 ± 0.07) mg/L and (40.98 ± 3.05) mg/L respectively. The resistance of K562/A02 cells to ADM was 28.06 times as that of K562 cells. After treatment of K562/A02 cell with DFO of 12.5, 25 and 50 µmol/L for 48 hours, the resistance of K562/A02 cells to ADM were increased by 24.95, 16.11 and 9.99 times respectively. When K562/A02 cells were incubated with different concentrations of DFO of 12.5, 25, 50 µmol/L for 48 hours, the apoptosis rat were (3.50 ± 0.30)%, (7.27 ± 0.32)% and (12.53 ± 1.21)% respectively. After co-culture with DFO and ADM for 48 hours, apoptosis rate were (6.13 ± 0.29)%, (9.57 ± 0.40)% and (18.97 ± 1.10)% respectively. The above apoptosis rates was much higher than that of control group (p < 0.05) and they were dose-dependent. In comparison between DFO + ADM group and DFO group, there was no significant difference (p > 0.05). Expression rate of BAX/BCL-2 increased. The levels of MDR1 mRNA reduced. Furthermore, expression of P-gp also decreased in K562/A02 cells. It is concluded that iron increase can promote K562/A02 cells growth and inhibit their apoptosis. Otherwise, iron-deprivation can induce K562/A02 cells apoptosis. DFO disturbs the iron metabolism and inhibits DNA synthesis of K562/A02 cells. This action of DFO may enhance the susceptibility of K562/A02 cells to apoptosis induced by chemotherapeutic drugs. The iron-deprivation may play a role in the treatment of leukemia with combination of DFO with other anticancer agents.
ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Apoptosis ; Deferoxamine ; pharmacology ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Humans ; Iron ; metabolism ; K562 Cells ; drug effects ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; bcl-2-Associated X Protein ; metabolism

· AIM:To investigate the prevalence of juvenile myopia and factors affecting its occurrence in Linxia Prefecture.· METHODS:Totally 8 683 juvenile students who were 6-18 years old were extracted as respondent with stratified cluster sampling method.The eyesight,diopter and axial length were detected,and the gender,age,ethnicity,eye behavior were collected by self-made questionnaire.· RESULTS:The prevalence of myopia was 42.80％.The myopic rates of all ethnic groups were as follows:Tibetan Nationality:59.05％,Han Nationality:46.71％,Dongxiang Nationality:46.36％,Tu Nationality:45.24％,Sala Nationality:41.30％,Baoan nationality:40.61％,Hui Nationality:31.97％.Myopia rate between each ethnic groups had statistical difference (x2 =44.08,P=0.007).Multivariate analyses revealed that outdoor activities during the break was the protect factor for myopia;age,using electronic products on weekends and holidays,using the same lighting in room while studying were risk factors for myopia.· CONCLUSION:The prevalence of myopia increase with age in Linxia.The prevalence in different ethnic groups is different.Education department and family should make joint efforts to increase the outdoor time,improve the environment for teenagers to reduce the occurrence and development of myopia.

OBJECTIVETo compare the clinical features in children with different control levels of asthma and to explore the factors influencing asthma control.

METHODSA cross-sectional study was performed on 115 children diagnosed with asthma between October 2013 and February 2014. All the patients were classified into two groups: fully controlled group (n=65) and non-fully controlled group (n=55), according to the Children Bronchial Asthma Prevention and Treatment Guideline (2008 version) and the asthma control test results. The differences of clinical features between the two groups were compared. The quality of life was evaluated by an asthma-related quality of life questionnaire. The main factors influencing asthma control were analyzed by the logistic regression method.

RESULTSThere were significant differences in the frequencies of respiratory tract infection and acute asthma attacks within the 3 months, and unplanned hospital visits due to acute asthma attacks between the fully controlled and non-fully controlled groups (P<0.05). The scores of asthma-related quality of life in the fully controlled group were significantly lower than in the non-fully controlled group in children under 7 years old. In contrast, the scores of asthma-related quality of life in the fully controlled group were significantly higher than in the non-fully controlled group in children at the age of 7-16 years (P<0.05). The logistic regression analysis showed that the patients without experiencing regular hospital visits (OR=7.715) and with allergic rhinitis (OR=5.531) had increased risks for poor asthma control and that the patients with other allergic diseases (eg. eczema, food allergy) had decreased risks for poor asthma control (OR=0.299).

CONCLUSIONSThe appearance of some clinical features suggests that the asthmatic children may be in the status of poor asthma control and need an active intervention. A poor asthma control status can result in a decreased quality of life. To improve the asthma control level, the incidence of allergic rhinitis should be reduced and a regular hospital visit should be performed in the children.

Adolescent ; Asthma ; drug therapy ; psychology ; Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; Humans ; Logistic Models ; Male ; Quality of Life

OBJECTIVEAlthough primary ciliary dyskinesia (PCD) is a group of inherited diseases, accurate diagnosis and appropriate clinical care to prevent and treat the complications could maintain patients' quality of life and normal life span. The diagnosis of PCD may often be delayed because it is frequently misdiagnosed as bronchitis, sinusitis and otitis. This study aimed to analyze and summarize the clinical features of PCD and explore diagnostic and differential diagnostic procedures in children.

METHODSPatients were all chosen from the inpatient department of Beijing Children's Hospital, Capital Medical University between 1990 - 2006. The tunica mucosa bronchiorum and/or nasal mucous membrane were gained through bronchoscope in children suspected to have PCD. The ciliary ultrastructures were analyzed through the electron microscope. The clinical features and procedures of the diagnosis and differential diagnosis in children with PCD were analyzed.

RESULTSThere were totally 26 children diagnosed as PCD with 10 (38.5%) Kartagener syndrome. All Kartagener syndrome children had mirror image dextrocardia with normal cardiac structure and situs inversus viscerum. The bronchoscopy performed in eight of 10 Kartagener syndrome children showed bronchus transposition. Twenty-six children came from twenty-five families. Although the siblings of four probands also had the symptoms of chronic cough with sputum, running nose and recurrent respiratory infections, only a boy and his sister were diagnosed as Kartagener syndrome simultaneously. Their parents and the other family members were healthy. Of the 26 patients, 11 were boys and 15 were girls. The median age at diagnosis was 8.7 years. The age of onset was between the second day after delivery and fifteen years old, median age was 3 years. The course of disease before diagnosis was eleven days to twelve years (median 3.5 years). All the children had the symptom of cough, 24 of which had productive cough. Seven cases were found to have clubbing fingers. Dynein arm defect was found in 10 children, 6 of them had total absence of dynein arms and 4 had decreased dynein arm numbers. Microtube derangements were found in 8 children. One Kartagener syndrome child had a normal cilia structure. Bronchiectasis, consolidation and increased lung markings were found in 8, 6 and 7 patients separately on the radiographic study. Twenty patients had sinusitis. Nine of sixteen children had decreased PEF, FEV1 and/or FEF 25 - 75 on the pulmonary function test. Fifteen culture samples obtained from 6 children's sputum and/or bronchoalveolar lavage fluid were positive for 8 strains of Pseudomonas aeruginosa, 5 strains of Streptococcus pneumoniae and 2 strains of Candida albicans. In 1 subject more than one organism were found in the same sample. Hearing lost and gastroesophageal reflux were detected in 3 of 4 and 3 of 5 examined children respectively.

CONCLUSIONSThe onset of PCD can occur from neonate to adolescence and usually has a chronic course. The common symptom of pediatric PCD was productive cough and significant growth retardation. The most common ultrastructural abnormalities associated with PCD were the total absence of dynein arms, decreased dynein arm numbers and microtube derangement. Some patients have normal ciliary structures. Bronchiectasis, consolidation and sinusitis were usually seen on the radiography. Pseudomonas aeruginosa and Streptococcus pneumoniae were the two common bacterial organisms obtained from sputum and/or bronchoalveolar lavage fluid of PCD children. Some patients have mixed infections. PCD children have high percentages of hearing lost and gastroesophageal reflux.

Adolescent ; Child ; Child, Preschool ; Diagnosis, Differential ; Female ; Humans ; Infant ; Kartagener Syndrome ; diagnosis ; Male

AIMTo determine the exact roles of prolactin (PRL) in the pathogenesis of rheumatoid arthritis (RA) and supply experimental basis for clinical treatment of RA, and to investigate the expression of matrix metalloproteinase-9 (MMP-9) in the synovium of adjuvant arthritis rats.

METHODSForty rats were divided into four groups (n = 10): (1) Normal control group (group A); (2) Adjuvant arthritis control group (group B); (3) Hyperprolactinemic adjuvant arthritis group (group C); (4) Hypoprolactinemic adjuvant arthritis group (group D). The content of PRL in the serum was detected by radio-immunoassay method. The activity of MMP-9 was analyzed by gelatin zymography. The alteration of MMP-9 immunoreactivity were investigated by means of immunohistochemistry in the synovium of all groups. The expressions of MMP-9 were investigated by Western blot in the synovium of all groups.

RESULTSCompared with group A, the activity and expression of MMP-9 of group B in the synovium were highly increased. The activity and expression of MMP-9 in the synovium were the most distinctive in group C. Compared with group B, the activity and expression of MMP-9 in the synovium were decreased in group D, but still higher than group A.

CONCLUSIONThe present results indicated that PRL might involved in the pathogenesis of RA by regulating the secretion of MMP-9 in the synovium.

Animals ; Arthritis, Experimental ; metabolism ; Arthritis, Rheumatoid ; physiopathology ; Male ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; Prolactin ; blood ; physiology ; Random Allocation ; Rats ; Rats, Wistar ; Synovial Membrane ; metabolism

Hepatitis B virus ; isolation & purification ; Hepatitis Delta Virus ; isolation & purification ; Humans ; Oligonucleotide Array Sequence Analysis ; Polymerase Chain Reaction

OBJECTIVETo investigate NK cell cytotoxicity to leukemic cell by NKG2D receptors and NKG2D ligands interaction upregulated by hydroxyurea (HU).

METHODSLeukemic cell lines OUN-1 and primary leukemic cells were cultured for 24 hours in the presence of HU, then the NKG2D ligands expressions were analyzed by flow cytometry (FCM). Isolated NK cells from healthy individual cultured for 72 hours in presence of IL-2 were used as effect cell, and leukemic cell line OUN-1 treated with HU was used as target cell, NK cell cytotoxicity against leukemic cell line was assessed using chromium-51 release assay.

RESULTSLeukemic cell lines showed upregulation of MIC A/B (MFI: 8.9 ± 0.9 vs 23.5 ± 3.4, P = 0.01) and ULBP2 (MFI: 14.5 ± 0.6 vs 33.5 ± 4.8, P = 0.03) following incubation with HU. HU also upregulated the NKG2DLs on primary leukemia cells from patients with acute myeloid leukemia. Treatment of OUN-1 with HU significantly increased the cytotoxicity of NK cells isolated from healthy individual \[(62.0 ± 5.6)% vs (76.0 ± 5.3)%, P = 0.02\], and the enhancing effect of HU was partly blocked by anti-NKG2D Abs \[(76.0 ± 5.3)% vs (46.0 ± 4.5)%, P = 0.00\].

CONCLUSIONHU selectively upregulated NKG2D ligand expression on leukemic cell lines, and enhanced NK cell cytotoxicity against leukemic cells through NKG2D receptors and NKG2D ligands interaction.

Cell Line, Tumor ; Humans ; Hydroxyurea ; pharmacology ; Killer Cells, Natural ; drug effects ; immunology ; Leukemia ; immunology ; Ligands ; NK Cell Lectin-Like Receptor Subfamily K ; immunology