OBJECTIVESTo establish a primary biliary cirrhosis (PBC) model by AMAM2 autoantigen injection into C57BL/6 mice.

METHODSMice of the model group were immunized intraperitonealy with 200 microl of purified recombinant AMAM2 autoantigen in complete Freund's adjuvant (CFA). Mice immunized with bovine serum albumin and CFA in the same way were used as negative controls. Sixty-six weeks later, mice were sacrificed and their sera were collected. Sera samples were assayed for AMAM2 autoantibody, alkaline phosphatase (ALP), ALT and total bilirubin (TBil). Their liver, stomach, muscle and kidney tissues were sectioned and stained using HE to observe the pathological changes.

RESULTSAntibodies to AMAM2 autoantigen were readily induced in the model group. The mice in the model group had no significant changes in the level of serum ALT and TBil but had an obvious increase of ALP (P<0.05). The stomach, muscle and kidney tissues showed no evident damage while the livers had obvious pathological changes, including bile duct degeneration or proliferation, and mononuclear cell infiltration.

CONCLUSIONThe AMAM2 autoantigen-induced PBC animal model was successfully established in C57BL/6 mice in our experiment and its characteristic biochemical and pathology are quite similar to that in the early stage of human PBC. This model may provide a useful experimental approach for further study of the pathogenesis and clinical treatment of human PBC.

Animals ; Autoantigens ; immunology ; Disease Models, Animal ; Liver Cirrhosis, Biliary ; etiology ; Mice ; Mice, Inbred C57BL ; Mitochondria ; immunology

OBJECTIVETo explore the effects of down-regulated tryptase expression in mast cells on the synthesis and release of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) of vascular endothelial cells.

METHODSTryptase-siRNA (small-interfering RNA) vector was constructed to inhibit tryptase expression in P815 cells. The medium of P815 cells treated by the tryptase-siRNA (RNAi-P815 group) or pure vector (P815 group) was collected and used to culture bEnd.3 cells. The messenger RNAs (mRNAs) of IL-6 and TNF-alpha in bEnd.3 cells and their protein levels in the medium were measured by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively.

RESULTSIL-6 and TNF-alpha mRNAs in bEnd.3 cells cultured in RNAi-P815-conditioned medium decreased significantly compared to those in P815-conditioned medium. Consistently, IL-6 and TNF-alpha protein levels in the medium of bEnd.3 of RNAi-P815 group were lower than those of P815 group.

CONCLUSIONReduced tryptase expression significantly inhibited the synthesis and release of IL-6 and TNF-alpha in vascular endothelial cells. RNA interference targeting tryptase expression may be a new anti-inflammatory strategy for vascular diseases.

Animals ; Cell Line ; Culture Media, Conditioned ; Down-Regulation ; genetics ; Endothelial Cells ; enzymology ; secretion ; Gene Expression Regulation, Enzymologic ; Interleukin-6 ; genetics ; secretion ; Mice ; RNA, Messenger ; genetics ; RNA, Small Interfering ; genetics ; Transgenes ; Tryptases ; genetics ; metabolism ; Tumor Necrosis Factor-alpha ; genetics ; secretion

OBJECTIVETo compare the long-term results of procedure for prolapse and hemorrhoids(PPH) and Milligan-Morgan(MM) hemorrhoidectomy in the treatment of third- and fourth-degree hemorrhoids.

METHODSNinety-one patients in PPH group and 120 patients in MM group, treated in our hospital from May 2001 to May 2005, were followed up. All the patients suffered with third- or fourth-degree hemorrhoids. The data including symptoms relief, complication and recurrence were compared between two groups.

RESULTSPPH and MM both significantly relieved bleeding (95.6% vs 92.7%), pain (93.1% vs 94.3%) and prolapse (93.4% vs 93.1%). There were no significant differences between two groups(P >0.05). PPH significantly relieved constipation compared with MM(60.0% vs 32.1%, P <0.05). No significant differences of complete relief rates between PPH group and MM group according to different degrees, types and prolapses of hemorrhoids were found(P >0.05). There were no significant differences in the overall complication rate(14.3% vs 12.7%), recurrence rates(12.1% vs 8.8%) and satisfactory degree (85.1 vs 88.2) between two groups as well.

CONCLUSIONThe long-term outcomes of PPH in the treatment of third and fourth-degree hemorrhoids are similar to Milligan-Morgan hemorrhoidectomy.

Adult ; Aged ; Aged, 80 and over ; Anal Canal ; surgery ; Digestive System Surgical Procedures ; methods ; Female ; Follow-Up Studies ; Hemorrhoids ; surgery ; Humans ; Male ; Middle Aged ; Surgical Stapling ; Surgical Stomas ; Young Adult

Child, Preschool ; Flow Cytometry ; methods ; Genetic Carrier Screening ; Granulomatous Disease, Chronic ; diagnosis ; genetics ; Humans ; Infant ; Male

BACKGROUNDMany studies have shown the superior efficacy of budesonide (BUD)/formoterol (FORM) maintenance and reliever therapy, but still lack evidence of its efficacy in Chinese asthma patients in a relative large patient-group. We finished this research to compare BUD/FORM maintenance and reliever therapy and high-dose salmeterol (SALM)/fluticasone (FP) maintenance plus an as-needed short-acting β(2)-agonist in Chinese patients with persistent uncontrolled asthma. This was a post hoc analysis based on a 6-month, multicenter, randomized, double-blind study (NCT00242775).

METHODSA total of 222 eligible asthma patients from nine centers in China were randomized to either BUD/FORM+as-needed BUD/FORM (160/4.5 µg/inhalation) (640/18 µg/d; n = 111), or SALM/FP+as-needed terbutaline (0.4 mg/inhalation) (100/1000 µg/d; n = 111). The primary endpoint was time to first severe exacerbation while secondary endpoints included various measures of pulmonary function, symptom control and quality-of-life.

RESULTSTime to first severe exacerbation over six months was lower with the BUD/FORM than with the SALM/FP treatment (risk ratio = 0.52, 95%CI 0.22 - 1.22), but the difference did not achieve statistical significance (P = 0.13). The cumulative number of severe exacerbations in the BUD/FORM group was lower than in the SALM/FP group (7.2% vs. 13.5%; risk ratio = 0.45, P = 0.028). BUD/FORM produced significantly better improvements in reliever use, cumulative mild exacerbations, symptom-free days (%), and morning/evening peak expiratory flow (PEF) than SALM/FP (P < 0.05 in all cases). The two groups achieved similar improvements in their time to first mild exacerbation, forced expiratory volume in one second (FEV(1)), asthma control questionnaire and asthma symptom scores, and percentage of nights with awakening(s). Both treatments were well tolerated.

CONCLUSIONSIn Chinese patients with persistent asthma, BUD/FORM decreased severe and mild exacerbations, decreased reliever use, increased symptom-free days, and improved morning/evening PEF compared with SALM/FP. There were no significant differences in time to first severe exacerbation or other assessments regarding daily asthma control between BUD/FORM and SALM/FP. BUD/FORM was more effective in this Chinese sub-group than in the total cohort involved in the original study.

Adolescent ; Adult ; Aged ; Asthma ; complications ; drug therapy ; physiopathology ; Budesonide ; administration & dosage ; adverse effects ; Double-Blind Method ; Ethanolamines ; administration & dosage ; adverse effects ; Female ; Forced Expiratory Volume ; Formoterol Fumarate ; Humans ; Male ; Middle Aged

Animals ; Anthelmintics ; pharmacology ; therapeutic use ; Culture Media ; Echinococcosis ; drug therapy ; parasitology ; Echinococcus granulosus ; drug effects ; growth & development ; pathogenicity ; ultrastructure ; Parasitic Sensitivity Tests

OBJECTIVETo investigate the effect of granulocyte colony stimulating factor (G-CSF) on myeloid-derived suppressor cells (MDSCs) in the bone marrow and peripheral blood, and explore the relationship between MDSC and graft-versus-host disease (GVHD).

METHODSBone marrow, peripheral blood and peripheral blood stem cells were obtained from 12 healthy hemopoietic stem cell donors before and on day 5 after G-CSF mobilization. Flow cytometry was employed to examine the number of MDSC, and the relationship between MDSC number and the incidence of GVHD was analyzed.

RESULTSIn normal physiological conditions, MDSC could be detected in the peripheral blood and bone marrow with a cell percentages of (1.35±0.35)% and (2.44±1.11)%, respectively, showing a significantly higher cell percentage in the bone marrow (P=0.015). On the 5th day after G-CSF mobilization, the percentage of MDSCs increased to (4.01±1.82)% in the peripheral blood and to (4.38±2.19)% in the bone marrow, showing no significant difference between them (P=0.083). The mobilization caused a significant increase in the number of MDSCs in the peripheral blood (P=0.047) but not in the bone marrow (P=0.761). The number of MDSCs in the collected samples showed a significant inverse correlation to the incidence of GVHD (P=0.048).

CONCLUSIONSMDSCs are present in the peripheral blood and bone marrow of healthy donors, with a greater number in the bone marrow. G-CSF can mobilize the MDSCs from the bone marrow to the peripheral blood to increase number of MDSCs in the peripheral blood, which may contribute to a lowered incidence of GVHD in hematopoietic stem cell transplantation (HSCT).

Adolescent ; Adult ; Bone Marrow Cells ; cytology ; Female ; Graft vs Host Disease ; prevention & control ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Hematopoietic Stem Cell Mobilization ; methods ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; T-Lymphocytes ; cytology ; drug effects ; metabolism ; Young Adult

OBJECTIVETo evaluate the reliability of the birth defects surveillance system in four counties with high prevalence of birth defects (Pingding, Xiyang, Taigu and Zezhou counties) in Shanxi province, China.

METHODSOne township was selected from each county as study site. The health workers chosen from township or village level were trained to visit families on the outcomes of each pregnancy who gave birth during year 2003 in the study site. The number of births and cases collected in the study were compared with that from the surveillance system. The number of births reported by surveillance system in four counties was also compared with the data from the local government. The criteria of evaluation were: 1) number of the missing report of births should < or = 5%, 2) the number of missing report on major external birth defects cases should < or = 10%. Researchers from the Peking University were responsible for examining the quality of surveillance in some terminal units of surveillance system.

RESULTSThe numbers of births reported in the study and from the surveillance system for four-township were 1043 and 997, respectively. 46 births were missing and the rate of misreporting for births was 4.4%. The numbers of birth defects cases reported in the study and from the surveillance system were 30 and 29, respectively. 1 case of birth defect as missed, and rate of misreporting for birth defects cases was 3.3%. The total number of births reported from surveillance was similar to that in the study in four counties, with a difference of 1.2%. Birth registry data was rather readable and special health workers responsible for surveillance work were present in all the terminal units of the surveillance system.

CONCLUSIONThe misreporting of births and cases existed in the birth defects surveillance system of the four counties in Shanxi province, but were lower than the allowable criteria. The surveillance units had better registration, reporting and administration of births and birth defect cases. Hence, the quality of the data from the surveillance system in these four counties was reliable.

Birth Certificates ; China ; epidemiology ; Congenital Abnormalities ; epidemiology ; Female ; Humans ; Infant, Newborn ; Population Surveillance ; Pregnancy ; Pregnancy Outcome ; Registries ; Reproducibility of Results

OBJECTIVE To explore the effect of total flavonoids of Rhododendra simsii (TFR) on improving cerebral ischemia/reperfusion injury (CIRI) and its relationship with STIM/Orai-regulated operational Ca2+influx (SOCE) pathway. METHODS Oxygen-glucose deprivation/reoxygenation (OGD/R) PC12 cells were used to simulate CIRI in vitro, and the intracellular Ca2+ concentration and apoptosis rate of PC12 cells were detected by laser confocal microscope and flow cytometry, respectively. The regulation of STIM/Orai on SOCE was analyzed by STIM/Orai gene silencing and STIM/Orai gene overexpression. The CIRI model was established by MCAO in SD rats. The activities of inflammatory cyto?kines IL-1, IL-6 and TNF-αin serum were detected by ELISA. The pathological changes of ischemic brain tissue and the infarction of rat brain tissue were detected by HE staining and TTC staining. The protein and mRNA expression levels of STIM1, STIM2, Orai1, caspase-3 and PKB in brain tissue were detected by Western blotting and RT-qPCR, respectively. RESULTS The results of in vitro experiment showed that the fluorescence intensity of Ca2+ and apoptosis rate in PC12 cells treated with TFR were significantly lower than those in OGD/R group, and this trend was enhanced by SOCE antagonist 2-APB. STIM1/STIM2/Orai1 gene silencing significantly reduced apoptosis and Ca2+overload in OGD/R model, while TFR combined with overexpression of STIM1/STIM2/Orai1 aggravated apoptosis and Ca2+overload. In the in vivo experiment, TFR significantly reduced the brain histopathological damage, infarction of brain tissue, the contents of IL-1, IL-6 and TNF-α in the serum in MCAO rats and down-regulated the expression of STIM1, STIM2, Orai1 and caspase-3 protein and mRNA in the brain tissue, and up-regulated the expression of PKB. The above effects were enhanced by the addition of 2-APB. CONCLUSION The above results indicate that TFR may reduce the contents of inflammatory factors and apoptosis, decrease Ca2+ overload and ameliorate brain injury by inhibiting SOCE pathway mediated by STIM and Orai, suggesting that it has a protective effect against subacute CIRI.

Objective To establish a community-based management model for heart failure patients under the professional guidance of upper first-class hospital staff.Methods Two hundreds heart failure (New York Heart Function Ⅱ-Ⅳ) patients aged from 35 to 85 in two communities of Chengdu city were divided into two groups by cluster randomization:the management group and the control group.The community hospital doctors were trained for the evaluation and management of heart failure according standardized guidelines by upper first-class hospital doctors,and responsible for the management of patients in the management group.Meanwhile,the management group patients also received self-care education.Patients in control group were treated by community doctors without special training.Data including the community hospital doctors' knowledge rate of heart failure,positive diagnosis rate,and the rate for standardized medication for heart failure; the patients' knowledge rate of heart failure,the rate of drug compliance,the rate of standardized drug taken for heart failure,the rate of self-care in daily-life,the quality of life,the iucidence of cardiovascular events,hospitalization time and cost were compared between the two groups.Results The community hospital doctors' knowledge rate of heart failure,the related knowledge for prevention and treatment on the causes of heart failure,the positive diagnosis rate,and the rate for standardized medication for heart failure [β receptor blocker 77.3％ (17/22); angiotensinconverting enzyme inhibitors 63.6％ (14/22)] were significantly higher than doctors in the control group (all P ＜ 0.05).There were 96 in the management group and 97 in the control group.Data were similar between the two groups at baseline.After (18.5 ± 0.5)months,the patient's knowledge rate of heart failure [100％ (96/96) vs.71.1％ (69/97)],the rate of drug compliance [78.1％ (75/96) vs.13.4％ (13/97)],the rate of standardized drug taken for heart failure[β receptor blocker:75.0％ (72/96) vs.8.2％(8/97) ; angiotensin-converting enzyme inhibitors:60.4％ (58/96) vs.10.3％ (10/97)],and the rate of self-care in daily-life [salt and food restriction:88.5％ (85/96) vs.29.9％ (23/97) ; blood pressure monitoring:83.3％ (80/96) vs.56.7％ (55/97) ; weight monitoring:78.1％ (75/96) vs.13.4％ (13/97)] were all significantly higher in the management group than in control group.For patients with New York Heart Function Ⅲ-Ⅳ,the score of the LiHFe questionnaire (43.7 ± 9.2 vs.49.5 ± 11.3),the incidence of cardiovascular events [63.3％ (19/30) vs.90.3％ (28/31)],the days of hospitalization [(8.2 ± 3.2) days vs.(13.9 ± 10.9) days],and the cost for hospitalization [(2873.3 ± 401.6) Yuan vs.(4525.8 ±6417.8) Yuan] were all significantly lower in the management group(n =30) than in the control group(n =31) (all P ＜ 0.05).Conclusions The community-based management model for heart failure patients in the community level is effective to improve the management and outcome in this cohort.