AIM: To examine whether lipoxin A_4 (LXA_4) induces apoptosis of rat renal interstitial fibroblasts and explore the mechanisms. METHODS: Rat renal interstitial fibroblasts (NRK-49F cells) were incubated in RPMI-1640 medium supplemented with 5% fetal calf serum and exposed to LXA_4 at the concentration of 10 nmol/L, 100 nmol/L or 1 ?mol/L for 24 hours. Prior to experiment, some cells were transfected with calpain 10 antisense oligodeoxynucleotide. Apoptosis of cells was recognized by double staining using fluorescent dye acridine orange and ethidium bromide, observed under laser scanning confocal microscopy and counted by flow cytometry following propidium iodide and annexin staining. Activity of caspase-3 was measured by colorimetric assay. The expression of calpain 10 mRNA was determined by RT-PCR. RESULTS: LXA_4 at the concentration of 100 nmol/L or 1 ?mol/L induced 9.83% or 33.82% apoptosis of cells, respectively. Treatment of cells with LXA_4 up-regulated the expression of calpain 10 mRNA and increased the activity of caspase-3. The transfection of the cells with calpain 10 antisense oligodeoxynucleotide inhibited the LXA_4-induced apoptosis, activity of caspase-3 and expression of calpain 10. CONCLUSION: LXA_4 at high concentration induceds apoptosis in rat renal interstitial fibroblasts via up-regulating of calpain 10 mRNA expression.

AIM: To find whether lipoxin A_4 (LXA_4) inhibits cell proliferation induced by TNF-? in rat mesangial cells, and to explore the molecular mechanisms of signal pathways of LXA_4 actions. METHODS: Cultured rat mesangial cells were growth-arrested and exposed to TNF-? with or without preincubation with LXA_4. Proliferation of mesangial cells was measured by MTT methods. Activities of STAT_3 were analyzed by electrophoretic mobility shift assay. Expression of cyclin E mRNA was assessed by RT-PCR. Cyclin E proteins were determined by Western blotting analysis. RESULTS: TNF-?-induced proliferation and increased mRNA and protein expression of cyclin E in mesangial cells were inhibited by LXA_4 in a dose-dependant manner. TNF-?-stimulation of the STAT_3-binding activities in mesangial cells was down-regulated by lipoxin A_4. CONCLUSION: Inhibitory effect of LXA_4 on TNF-?-induced mesangial cell proliferation is mediated by Jak_1/STAT_3 signal pathway.

Objective To examine whether lipoxin A4(LXA4) has an antagonistic effect on interleukin (IL)-1?-induced synthesis of IL-6 in glomerular mesangial cells, and to explore its mechanism. Methods Cultured glomerular mesangial cells (GMCs) of rat were treated with IL-1?, with or without preincubation with LXA4. Protein secretion of IL-6 in supernatants was examined analyzed by enzyme-linked immunosorbent assay (ELISA). Expression of IL-6 mRNA was determined by RT-PCR. The expression of Src homology 2 (SH2) containing protein-tyrosine phosphatase 2 (SHP-2) was assessed by immunoblotting. Activities of DNA-binding of nuclear factor-kappa B (NF-?B) were measured by electrophoretic mobility shift assay (EMSA). Results The secretion of protein and expression of mRNA of IL-6 in GMCs stimulated by IL-1? were inhibited by LXA4 in a dose-dependent manner. LXA4 reduced the phosphorylation of SHP-2 and activities of NF-?B. Pretreatmnet of GMCs with NF-?B inhibitor pyrrolidine dithio-carbamate (PDTC) blocked both the secretion of IL-6 protein and activation of NF-?B induced by IL-13- Conclusion LXA4 antagonists IL-1?-induced synthesis of IL-6 in GMCs through the pathway of SHP-2/NF-?B signal transduction.

Objective To examine whether lipoxin A4(LXA4) induces apoptosis of rat renal interstitial fibroblasts and explore the mechanism concerned.Methods Rat renal interstitial fibroblasts (NRK 49F cells)were incubated in RPMI 1640 medium supplemented with 5%fetal calf serum and exposed to LXA4 at the concentration of 10 nmol/L, 100 nmol/L or 1 ?mol/L for 24 hours. Prior to experiment,some NRK 49F cells were transfected with Smac antisense oligodeoxynucleotide. Apoptosis of NRK 49F cells was recognized by double staining using fluorescent dye acridine orange and ethidium bromide,and observed under laser scanning confocal microscopy and counted by flow cytometry following propidium iodide and annexin staining. Activity of caspase 3 was measured by colorimetric assay. The expression of Smac was determined by Western blotting analysis.Results LXA4 at the concentration of 100 nmol/L or 1 ?mol/L induced apoptosis of 9 83%or 33 82%of NRK 49F cells respectively, and reduced the cells of S and G2～M phase and increased the cells of G0～G1 phase in a dose dependent manner. Treatment of NRK 49F cells with LXA4 up regulated the expression of Smac protein and increased the activity of caspase 3. The transfection with Smac antisense oligodeoxynucleotide inhibited the LXA4 induced apoptosis and expression of Smac in NRK 49F cells. Conclusion LXA4 at high concentration can induce apoptosis of rat renal interstitial fibroblasts via the up regulation of Smac expression.

Thirty patients with malignant obstructive jaundice were treated with biliary stent implantation+brachytherapy+conformal radiotherapy (study group; n=15) or biliary stent implantation alone (control group; n=15). Total bilirubin (TBIL) levels significantly declined within 1 month in both groups. However, at 6 months, TBIL values began to increase in the control group and continuously declined in the study group. Maximum tumor diameter increased in the control group, while decreased in the study group (remission rate, 13/15 ). As for the study group, the survival rate at 0. 5, 1, and 2 years was 15/15,14/15, and 10/15, respectively, higher than the control group (15/15,5/15,and 1/15) . Combining biliary stent implantation with brachytherapy and conformal radiotherapy might be a safe and effective treatment of choice for patients with malignant obstructive jaundice.

Objective To investigate the factors associated with delay in decision to seek treatment in patients with acute myocardial infarction(AMI) in Beijing. Methods This prospective,cross-sectional,multicenter survey was conducted from November 1,2005 and December 31 ,2006. The participants consisted of 799 patients with STEMI admitted within 24 h of symptom onset to 19 hospitals in Beijing. Data were collected by semi-structured interviews and medical records review. The patients were categorized into an early decision group and the a late decision group based on the 30 min cut-off. Results The median(25%,75%) decision delay in STEMI patients was 60(20, 180)min. Factors associated with late decision in an univariate analysis were age ≥65 years, retirement or unemployment, history of myocardial infarction,symptom onset at home and intermittent symptoms, whereas presence of bystanders such as friends,coworkers or even strangers,unbearable symptoms,dyspnea,sweating,syncope and attribution of symptoms to cardiac origin were related to early decision. Multivariate logistic analysis showed that history of myocardial infarction,absence of syncope, intermittent symptoms,bearable symptoms and attribution of symptoms to noncardiac origin were independent predictors of decision delay＞30 min. Patients in the early decision group had more chances to receive acute reperfusion therapies(P=0.001) and shorter time intervals from symptom onset to reperfusion therapies(P＜0.001). Conclusions To a great extent patients with AMI in Beijing delayed in decision to seek treatment. History of myocardial infarction, symptom characteristics and symptom attribution were associated with decision delay.

BACKGROUND:The mechanism underlying orthodontic-induced external root resorption is not yet clear, and it differs individual y. Kidney deficiency has been proved to be related to bone diseases which mediated by different cytokines. Interleukin-17 is an important cytokine involved in external root resorption. So figuring out whether kidney deficiency and interleukin-17 are related to root resorption wil be helpful for etiological research.
OBJECTIVE:To explore the relationship between kidney deficiency physique, interleukin-17 and root resorption during orthodontic treatment in rats.
METHODS:Thirty-six Wistar rats were selected and equivalently randomized into two groups, fol owed by modeled into kidney deficiency (kidney deficiency group) or injected with normal saline (control group), respectively. Afterwards, the right maxil ary of each rat served as an orthodontic force model, and the left maxil ary as a non-orthodontic force model. Al rats were respectively sacrificed under general anesthesia at the 3, 7 and 14 days after given orthodontic force. Then, the mesial surface of the root of maxil ary first molars and the expression level of interleukin-17 were observed through hematoxylin-eosin staining and immunohistochemical method.
RESULTS AND CONCLUSION:Histological observation showed that significantly increasing root resorption in a time-dependent manner could be observed, and there were various absorbed lacunae of osteoclasts on the enamel in the kidney deficiency orthodontic force group. The alveolar bone resorption and widened periodontal membrane appeared in the control orthodontic force group. While no remarkable root and alveolar bone resorptions were found in the other two non-orthodontic force groups. The expression level of interleukin-17 in the kidney deficiency orthodontic force group was higher than that in the control orthodontic force group;the expression level of interleukin-17 in the kidney deficiency non-orthodontic force group was higher than that in the control non-orthodontic force group. In conclusion, kidney deficiency patients are easy to develop root resorption, the mechanism of which is maybe relevant to the upregulation of interleukin-17.

AIM: To study and evaluate the changes of two main kinds of voltage-gated K+ currents in human atrial fibrillation (AF) and to discuss the role of these changes in the atrial electrical remodeling (AER) caused by AF. METHODS: Specimens of human atrial appendage were obtained from 36 RHD patients (18 with chronic AF and 18 without AF). Single atrial myocytes were acutely dissociated by tissue chunk enzymatic digestion. I_~to1 and I_~Kur in the two groups were measured respectively with the patch-clamp technique in a whole-cell configuration and the I-V curves were compared. RESULTS: I_~to1 and I_~Kur amplitudes in AF groups were significantly reduced and the current densities of both I_~to1 and I_~Kur in AF patients were lower than those in NAF patients. CONCLUSION: The reduction of I_~to1 and I_~Kur may be related to changes in atrial conduction, refractory period and may constitute two main parts of the major mechanisms in the AER of chronic AF. Whether exists a relation between changes of the above K+ currents and that of other ionic currents and the AF initiation and perpetuation deserves further investigation. [

Objective To investigate changes in high mobility group box-1 protein ( HMGB1 ) level in brain tissues with severe sepsis, and the relationship between HMGB1 and septic brain injury.Methods Forty wild C57BL/6 mice were randomly ( random number) divided into 4 groups: sham group, sepsis group, cerebroventricular injection control group, and sepsis with BoxA ( HMGB1 inhibitor) cerebroventricular injection group.Septic model was reproduced by cecal ligation and puncture, and the cerebroventricular catheterization model was established by motorized mice brain stereotaxic instruments.After septic challenge, 1 μg BoxA was injected into the ventricle of brain via cerebroventricular catheter immediately.Mice were sacrificed and brains were harvested at 24 h after sepsis, and hippocampus tissue was separated immediately.Expressions of brain HMGB1 and caspase-3 changed in apoptotic neurons and brain injury were determined by brain tissue immunofluorescence, Western blotting, TUNEL and HE staining respectively.One-way analysis of variance ( ANOVA) for analyzing inter-group differences, student t test for comparing difference between two groups . Results (1) HMGB1 expression in hippocampus was significantly enhanced in the septic group compared to the sham group [ (22.74 ±9.29) vs.4.57 ±2.18, P<0.01].(2) Compared to the sham group, neuronal apoptosis [ (35 ±9.17) vs.(1.67 ±1.53) , P<0.01) and caspase-3 expressions [ (16.79 ±8.17) vs.( 3.39 ±2.09), P<0.05] were significantly increased in hippocampus with aggravated brain injury in the septic group.(3) Cerebroventricular injection of BoxA significantly inhibited HMGB1 in hippocampus [ (2.66 ± 2.06) vs.( 22.74 ±9.29), P<0.01];(4) Cerebroventricular injection of BoxA obviously alleviated acute brain injury, and decreased neuronal apoptosis [ ( 12 ±4.36 ) vs.( 35 ±9.17 ) , P <0.01 ] as well as caspase-3 activity [ (4.10 ±2.11) vs.(16.80 ±8.17), P<0.05].Conclusions The elevated expression of brain HMGB1 is closely related to pathogenesis and development of septic brain injury, and treatment with antagonist towards brain HMGB1 can markedly attenuate acute brain injury following severe sepsis.

OBJECTIVETo explore and compare the clinical effects of three immuno-potentiators and their influence on immune function in preventing and treating recurrent respiratory tract infection (RRI).

METHODSSeventy-two children with RRT were assigned to three groups, the 23 patients in the M group treated with milkvetch extract oral liquid, the 23 in the P group treated by P-transfer factor and the 26 in the U group treated by Utilins injection. Clinical effect was compared among three groups after treatment, and changes of T cell subgroups as well as immune antibodies were detected before and after treatment.

RESULTSThe markedly effective rate in the M, P, and U group was 69.6%, 65.2%, and 73.0% respectively, and the total effective rate 87.0%, 82.6%, and 92.3%, showing an insignificant difference among them (all P>0.05). After treatment, the levels of CD3+, CD4+ and CD4+/CD8+ rose obviously in the three groups (all P<0.05); levels of CD8+ in the M group and the P group lowered significantly (P<0.05, P<0.01), but with no significant difference among three groups in the changes of T cell subgroups (all P>0.05). Serum levels of IgG in all the three groups, IgA in the P group and the M group, and IgM in the M group and the U group rose significantly (P<0.05 or P<0.01), with statistical difference presented in comparing of IgA level in the P group with that in the other two groups (P<0.01).

CONCLUSIONThe clinical effects and the outcomes of immunological indexes' changing are similar in RRI patients treated by the three immuno-potentiators. They all can enhance the immunological function of the organism, strengthen the disease-resistant ability of patients, and reduce the incidence of RRI. Among them, the milkvetch extract oral liquid is worthy of spreading due to its lower cost, simple administration, exemption from painful injection, and good compliance.

Administration, Oral ; Astragalus Plant ; chemistry ; Child ; Child, Preschool ; Drugs, Chinese Herbal ; administration & dosage ; pharmacology ; therapeutic use ; Female ; Humans ; Immunoglobulins ; blood ; Infant ; Male ; Respiratory Tract Infections ; blood ; drug therapy ; immunology ; prevention & control ; Retrospective Studies ; Secondary Prevention ; T-Lymphocyte Subsets ; drug effects ; immunology ; Treatment Outcome