Breast cancer susceptibiIity gene 1( BRCA1)is a tumor suppressor,but mutated get BRCA1 is cIoseIy reIated to the deveIopment of breast cancer. Current study has reveaIed that BRCA1 can get invoIved in the DNA damage repair process as a key mediator. DNA doubIe-stranded break (DSB)is the most serious form in DNA Iesions,and BRCA1 pIays an important roIe in repairing DSB through reguIation of homoIogous recombination( HR). In this articIe,the moIecuIar mechanism of BRCA1 in reguIating HR is reviewed with reference to the activity of functionaI domains in BRCA1 struc-ture,the mutations occurring in main domains of BRCA1,the reIationship of BRCA1 with BRCA2, Rad51 or CtIP,and phosphoryIation of BRCA1. In addition,the association of the defective BRCA1-mediated HR repair mechanism with the sensitivity to different DNA damaging agents and synthetic IethaIity in tumor ceIIs is aIso addressed.

0.05). CONCLUSION: Anethole trithione has proved efficacy for primary Sjogren's syndrome including xerostomia and xerophthalmia.

Objective To investigate whether B-cell activating factor (BAFF) involved in the patho-genesis of lupus nephritis (LN) by regulating phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling. Methods Twenty-eight lupus nephritis patients and 20 controls were included in this study. The clinical data were collected. BAFF levels in plasma were measured by ELISA, and the relationship between systemic lupus erythematosus disease activity index (SLEDAI) and BAFF were analyzed. The mRNA and protein levels of BAFF, phosphorylated-PI3K (p-PI3K), phosphorylated-Akt (p-Akt), phosphorylated-mTOR (p-mTOR) and Bcl-2 in kidney tissues were measured using real-time polymerase chain reaction (RT-PCR) and Western blotting. Data were analyzed using Mann-Whitney U test and Spearman correlation analysis. Results ①Plasma BAFF levels were significantly higher in LN patients [(580 ±45) ng/L] compared with controls [(208 ±30) ng/L](Z=-5.856, P<0.01), and significant positive correlation was found between plasma BAFF levels with SLEDAI (r=0.723, P<0.01). ② Plasma BAFF level in LN patients was positively correlated with 24 h UP and anti-dsDNA titers (r=0.381, 0.461, P<0.05). The protein level of BAFF in kidney tissues was positively correlated with 24 h UP and anti-dsDNA titer (r=0.469, 0.489, P<0.05).③The mRNA levels of BAFF, p-PI3K, p-Akt, p-mTOR and Bcl-2 in kidney tissues were increased in patients compared to controls[5.8±1.8 vs 2.1±0.7, Z=-4.915, P<0.01;6.7±0.9 vs 1.71±0.53, Z=-5.857, P<0.01;5.6±0.9 vs 1.8 ±0.5, Z=-5.751, P<0.01; 5.6 ±1.4 vs 1.6 ±0.4, Z=-5.291, P<0.01; 2.11 ±0.36 vs 1.33 ±0.22, Z=-4.844, P<0.01].④The protein levels of BAFF, p-PI3K, p-Akt, p-mTOR and Bcl-2 in kidney tissues were increased in patients compared to controls [0.72±0.19 vs 0.31±0.05, Z=-4.747, P<0.01;0.73±0.11 vs 0.33±0.09, Z=-5.834, P<0.01;0.77±0.06 vs 0.22±0.07, Z=-5.855, P<0.01;1.18±0.27 vs 0.47±0.13, Z=-5.416, P<0.01;2.08±0.37 vs 1.32±0.18, Z=-4.998, P<0.01]. Conclusion The findings of this study indicate that BAFF may participate in the pathogenesis of LN by regulating PI3K/Akt/mTOR signaling.

Objective To investigate the influence of salmeterol with fluticasone on airway inflammation of patients with acute exacerbation chronic obstructive pulmonary disease (COPD).Methods 40 COPD patients in the stage of acute exacerbation were randomly divided into salmeterol with fluticasone group( A group) and controll group (B group).Bronchial alveolar lavage( BAL) was performed as usual.The concentrations of IL-8 and TNF-α in bronchial alveolar lavage fluid(BALF) were measured by ELISA.The results were compared with that of 18 healthy volunteers.Results The levels of IL-8 and TNF-a in BALF of patients in A group(10.60 ± 1.42) μg/L, (14.80 ± 2.05) μg/Land B group( 10.77 ± 1.98) μg/L, (14.70 ± 2.03) μg/L were significantly higher than that of C group (3.40 ±0.65)μg/L, (4.67 ± 1.01) μg/L( all P <0.01) ;Before treatment,the levels of IL-8 and INF-α in BALF of A group( 10.60 ± 1.42)μg/L,(14.80 ±2.05) μg/L and B group( 10.77 ± 1.98) μg/L,(14.70 ±2.03) μg/L had no significant differences (all P > 0.05) ,and the concentrations of IL-8 and TNF-a in BALF in group A (4.39 ± 0.92)μg/L,(5.84 ±1.26) μg/L were significantly lower than that in group B(9.69 ± 1.43) μg/L, (12.88 ± 2.51) μg/L after two weeks treatment ( all P < 0.01).Conclusion Salmeterol with fluticasone could inhibit airway inflammation of COPD patients in the stage of acute exacerbation.

OBJECTIVE To study the effect of valproic acid ( VPA) on radiosensitivity to MCF7 breast cancer cells. METHODS MCF7 cells were pretreated with VPA 0.5 and 1 mmol.L-1 for 0, 24, 48 and 72 h respectively, irradiated with 8 Gy lR, and at 6 h post-lR, the γ-H2 AX foci formation in MCF7 cells was tested by immunofluorescence assay. MCF7 cells were pretreated with VPA 0.5 and 1 mmol.L-1 for 72 h, irradiated with 4 Gy lR, and at 48 h post-lR, the cell survival rate was detected by MTT assay. MCF7 cells were pretreated with VPA 0.5 mmol.L-1 for 24 h, and then irradiated according to the amount of cells: 2 Gy (500 and 1000 cells per plate), 4 Gy (2000 and 4000 cells per plate), 6 Gy (8000 and 16000 cells per plate), and the cloning efficiency was calculated. MCF7 cells were pretreated with VPA 0.5 and 1 mmol.L-1 for 0, 24, 48 and 72 h respectively and the cell cycle profile was analyzed via flow cytometry. RESULTS After treatment with VPA alone for 24 h, MCF7 cells showed a significant increase in the amount of γ-H2 AX foci formation ( P < 0. 01). lt was also found that VPA increased lR-induced γ-H2 AX foci formation, which obviously prolonged the pretreatment time of VPA(P<0.01) in a time-dependent manner(r=0.98, P<0.05). VPA 0.5 and 1 mmol.L-1 had the same effect on γ-H2 AX foci formation. Furthermore, VPA was able to cause a significant decrease in lR-induced clonogenic survival but an increase in lR-induced cytotoxicity by MTT assay. Also, VPA alone decreased the plating efficiency of MCF7 cells. However, the cycle profile of MCF7 cells treated with both VPA 0.5 and 1 mmol.L-1 was not changed. CONCLUSION Without affecting the cell cycle profile, both the safe and critical dose of VPA used in clinical epilepsy treatment can significantly increase the accumulation of DNA double strand breaks in the cells and sensitize the cells to lR treatment, suggesting that VPA can induce radio-sensitization of breast cancer cells.

Objective To explore the circadian rhythm of interleukin (IL)-6 in collagen induced arthritis (CIA) rats and investigate the effectiveness and safety of methotrexate (MTX) administered according to IL-6 rhythm.Methods Serum IL-6 concentrations of CIA and normal rats at different time points were measured by enzyme-linked immunosorbent assay (ELISA).CIA rats were randomly divided into the experimental group A,experimental group B and control group.MTX (1/7 mg·kg-1 ·d-1) was administered once a day when the IL-6 level began to increase or decrease in the experimental group,while MTX (1 mg/kg) administered once a week in the control group.Arthritis scores and leukocyte counts were observed.The production of IL-6 and C reactive protein (CRP) levels in the serum were measured.Moreover,histological changes in the ankle joint were examined.One-way analysis of variance (ANOVA),two independent sample t test were used to evaluate the experimental data.Results The plasma IL-6 levels in CIA rats were different at different time points,which began to increase at 18:00 and decrease at 6:00.Arthritis score in the experimental group A (4.8±0.7)was lower than that in the control group (5.8±1.0,t=2.256,P=0.0406) and experimental group B (5.5±0.5,t=2.393,P=0.0313).The levels of TNF-α [(185±21) ng/L],IL-6 [(99±6) ng/L],IL-1β[(20.1±1.6) ng/L] and CRP[(1251±282) μg/L] in the experimental group A were significantly lower than those in control group [TNF-α:(207±10) ng/L,t=2.726,P=0.016 4;IL-6:(100±6) ng/L,t=2.669,P=0.0183;IL-1β:(22.0±1.3) ng/L,t=2.814,P=0.0138;CRP:(1 417±278) μg/L,t=2.369,P=0.0327].The level of IL-6 in the experimental group A[(93±6) ng/L] was lower than that in the experimental group B [(99±6) ng/L,t=2.323,P=0.0358].Compared with the control group [(9650±1062)/μl],the counts of leukocyte in the experimental group A [(4595±603)/μl,t=3.841,P=0.0064] and experimental group B [(3833±585)/μl,t=4.442,P=0.003] were significantly lower.Compared with the control group (9.1 ±2.0),histopathology scores in the experimental group A (6.6±1.3,t=2.606,P=0.015) and experimental group B (7.4±1.3,t=3.857,P=0.0007) were significantly lower.Conclusion The plasma IL-6 levels in CIA rats have shown evident circadian rhythm.There-fore,once a day administration is better than once a week.The therapeutic effect of RA may be improved by administering MTX at the time points according to the circadian rhythm of IL-6.

Objective To explore the survival condition of hemodialysis patients in Ningxia Hui Autonomous Region. Methods Interviewed 15 patients with hemodialysis by applying Modified Grounded Theory Approach put forward by KinoSitaYasuHito,a Japanese scholar,the data of which were from qualitative inductive comparative analysis. Results As for the survival condition of hemodialysis patients in Ningxia,two relative themes were extracted, Helpless dialysis life Desire to return to society, the former contained 2 subtopics of hardship in life and susceptible mood, the latter contained 2 subtopics of cherish life and desire for care. Conclusion We should set up a social supporting system to improve the living condition of hemodialysis patients with the purpose of helping them return to the society.

Objective Production of autotoxin protein in sf9 insect cells with biological activity. Methods Autotaxin cDNA was cloned into pFastBacTMHTA from melanoma cell by extraction of total RNA using TRIzol method and RT-PCR. Bacmid-ATX is isolated from transformed competent bacterial DH10 which carries Bac genomic sequences and transfected into sf9 using lipofectamine 2000. Recombinant ATX virus was amplified in sf9 and further used for infection and expression of ATX protein. Two step purification product using HistrapTMHP and Hiload 16/600 Suerdex 200pg was determined for lysophospholipase D (lysoPLD) activity. Results Correct insertion of PCR fragment is confirmed by BamH I/Xho I digestion and sequencing. ATX virus can infect sf9 and induced enzymatic activity. Column purification and SDS-PAGE resulted 95% in purity and 6mg/liter in yield with significant lysoPLD activity. Conclusion ATX Baculovirus was successfully constructed that can infect sf9 cells and express active lysoPLD. Production of active ATX can be used for crystalography studies and screening for small pharmaceutical inhibitors.

Objective:To develop a two-step method for purification of monoclonal antibody rhTF243 protein from mouse ascites by using hydrophobic charge induction chromatography(HCIC) and affinity chromatography with protein A sepharose CL-4B.Methods:The ascites was first purified by HCIC after centrifugation and filtration.Then the fraction containing the protein of interest was directly purified by affinity chromatography with protein A sepharose CL-4B.Results:The purity of the obtained monoclonal antibody was up to 97% with recovery of 73% and of high activity.Conclusion:The method for purification of monoclonal antibody is developed using HCIC and Protein A affinity chromatography and the obtained antibodies are of high purity and activity.

Objective:To Studythe extracellular matrix metalloproteinase inducer (CD147) changes in patients with systemic lupus erythematosus (SLE), and to study thecorrelation of CD147 level and athero-sclerosis in SLE.Methods:Eighty patients with SLE in total were divided into intimal thickening group, (24 cases, group A) and normal intimal group (56 cases, group B) according to carotid intimamedia thickness (IMT) checked by carotid ultrasonography. In addition, their age, bodymass index, blood pressure, seral total cholesterol (TC), high density liptein cholestero (HDL-C), low density lipoprotein cholestero (LDL-C), triglyceride (TG), urinary protein quantitative test(24 h), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anticardiolipin antibody, serum creatinine level, course of the disease, and treatment regimens were collected. Thirty-five healthy people were set as the control group (group C). The levels of serum CD147 were measured by enzyme-linked immuno sorbent assay (ELISA) in 3 groups. The correlation between the serum CD147 level of SLE patients and atherosclerosis was analyzed. The statistical analysis was carried out with independent t-test, chi-square test, analysis of variance, Spearman correlation and Logistic regression. Results:① Levels of serum CD147 in group A [ (238±30) pg/ml] were significantly higher than those in group B [(198±30) pg/ml] and group C [(150±26) pg/ml, F=67.908, P<0.01]. ② Body mass index, hypertensive ratio,total blood cholesterol,urine protein quantitative test (24 h), systemic lupus erythematosus disease activity index (SLEDAI), serum CD147 index in group A were significantly higher than those in group B ( P<0.05). ③ In Logistic regression analysis, serum CD147 [ OR (95% CI)=1.039(1.014, 1.065), P<0.05], urine protein quantitative (24 h) [ OR (95% CI)=2.598(1.033, 6.534), P<0.05] were independently relevant factors affecting carotid artery IMT. Conclusion:Serum CD147 is an independent risk factor for carotid intimamedia thickness in SLE patients.