Background and purpose:Chemotherapy is the important way of breast cancer treatment, but the drug-resistance has attracted special attention. The emergence of drug resistance is closely related to the abnormal enhancement of DNA-damage repair. Both Kif4A and PARP-1 are important molecules of DNA repair. The research investigated the function of Kif4A in epirubicin up-regulating the activity of PARP-1 in breast cancer cells and possible significance. Methods:Western blot was used to detect the expression of Kif4A and PARP-1 after treatment with epirubicin in MDA-MB-231 and MCF-7 cells; the expression of PARP-1 and its activity were detected after high expression of Kif4A and treatment with epirubicin;FCM was used to detect cell apoptosis after treatment with epirubicin combined with PARP-1 inhibitor 3-ABA. Results:Epirubicin up-regulated PARP-1 activity and induced low expression of Kif4A in breast cancer cells, both of them showed dose-dependent and time-dependent. After high expression of Kif4A, the activity of PARP-1 was inhibited and the apoptosis of cells increased, epirubicin partially reversed the activity of PARP-1 inhibited by high Kif4A expression. Both of epirubicin and 3-ABA induced cell apoptosis, combination of them further increased cell apoptosis compared with alone used (P<0.05). The results also showed the apoptosis rate of MDA-MB-231 cells induced by epirubicin, PARP-1 inhibitor 3-ABA and high expression Kif4A was higher than that of MCF-7 cells (P<0.05). Conclusion:Epirubicin increases the activity of PARP-1 dependent on the low expression of Kif4A in breast cancer cells. Kif4A might become a novel target for overcoming resistance of epirubicin.

Objective To ob se rve the effects of danazol on hypothalamus-pituitary-gonad axises and expressi ons of hypothalamic GnRH and pituitary GnRH receptor mRNA in female rats. Methods Female rats at 5 days of age were given a sin gle subcutaneous injection of 300 ?g danazol to induce true precocious puberty. Animals were divided into 3 groups: normal control, model group and vehicle gro up. The day of vaginal opening from 25 days of age was monitored, and the establ ishment of first estrus cycle from the day of vaginal opening was investigated b y examination of vaginal smears. The weights of body, pituitary, adrenal, uterus and ovary were measured to identify the developmental status of main organs. Th e expressions of hypothalamic GnRH and pituitary GnRH receptor mRNA were assayed by semi-quantitative RT-PCR. Results Female rats treated with danazol significantly (P

Female ; Heart Septal Defects, Atrial ; complications ; Humans ; Levocardia ; complications ; Situs Inversus ; complications ; Young Adult

Objective:To evaluate the outcomes of lesser arc perilunate injuries (Perilunate disloca-tions)treated with arthroscopically assisted mini-invasive reduction and fixation.Methods:Between 2012 and 2014,5 patients who had a perilunate dislocation were treated with arthroscopically assisted re-duction and percutaneous fixation.The mean follow-up was 17.8 months (range,10 to 32 months). Clinical outcomes were evaluated on the basis of range of motion;grip strength;Mayo wrist score;Quick disabilities of the arm,shoulder and hand questionnaire;and patient-rated wrist evaluation score.Radio-graphic evaluations included carpal alignments and any development of arthritis.Results:The range of flexion-extension motion of injured wrist averaged 84% of the values for contralateral wrist.The grip strength of the injured wrist averaged 90% of the values for the contralateral wrists.The mean Quick Disabilities of the arm,shoulder and hand score was 1 ,and the mean Patient-Rated Wrist Evaluation score was 5 .According to the Mayo wrist scores,the overall functional outcomes were rated as excellent in all the patients.Reduction obtained during the operation was maintained within normal ranges in all the patients.Arthritis had not developed in any patient at the end of the follow-up.Conclusion:Arthroscopic mini-invasive reduction with percutaneous fixation is a reliable and favorable alternative in the treatment of perilunate dislocations according to our early results.

Objective To observe the activities of serum peroxidase capacity,and lipid peroxidation of children from Kaschin-Beck disease (KBD) areas of Xinghai county in Qinhai province,and to explore the relationship between antioxidant capacity and KBD.Methods Sixty four KBD and forty six health subjects without KBD were chosen from KBD endemic areas,which included primary schools of Tangnaihai,Xialujuan and Qushian of Xinghai county in Qinghai province,and fifty nine age-matched healthy control subjects without KBD were from a non-KBD endemic area,Nanfan primary school of Chang'an county in Shaanxi province.Twenty patients with KBD and twenty control subjects from KBD areas and non-KBD area were extracted by simple random sampling method.2,3-DAN fluorescence technique was used to test the hair and blood selenium.The biochemical techniques were used to test the indicators of oxidative stress including malondialdehyde(MDA),antioxidant enzyme activities,total antioxidant capacity(T-AOC),serum superoxide dismutase(SOD),catalase(CAT) and glutathione peroxidase(GSHPx).ResultsAll patients with KBD had significantly lower serum GSH-Px activities[ (59.53 ± 25.23)kU/L] and selenium levels in hair[ (67.64 ± 17.28)μg/L] and blood[(36.27 ± 13.29)μg/L],respectively,than that of control subjects from KBD areas [ ( 91.88 ± 22.99 ) kU/L,( 153.32 ± 24.31 ) μg/L,( 63.06 ± 13.66) μg/L ] and nonKBD areas[ ( 122.68 ± 41.74)kU/L,(242.35 ± 38.56)μg/L,(98.93 ± 17.18)μg/L,all P ＜ 0.05].Serum MDA levels in KBD patients[ (4.64 ± 1.11 )μmol/L] were significantly higher than that in control subjects from KBD [(3.31 ± 1.22)μmol/L] and non-KBD areas[ (3.43 ± 1.29)μmol/L,all P ＜ 0.05].On the other hand,T-AOC,SOD and CAT activities were significantly higher in both KBD[(19.80 ± 6.64),(55.80 ± 8.14),(16.45 ± 5.61 ) kU/L] and control subjects[ (21.71 ± 8.82),(57.45 ± 6.96),(15.63 ± 9.18)kU/L] from KBD areas than that of control subjects from non-KBD area[ (13.56 ± 5.38),(42.79 ± 8.10),(6.05 ± 2.71 )kU/L,all P ＜ 0.05 ].Hair selenium levels,blood selenium levels and GSH-Px activity of control subjects from KBD areas were,respectively,significantly lower than that in control subjects from non-KBD area(all P ＜ 0.05).Conclusions These findings strongly confirm the evidence that KBD patients are susceptible to oxidative stress.The results also show the increase in antioxidant enzymes,which could probably be due to adaptive response to pro-oxidant in KBD state.Hence,there seems to be an imbalance between oxidant and antioxidant systems in KBD patients.

The chemical constituents from lipophilic parts in the roots of Angelica dahurica var. formosana cv. Chuanbaizhi were studied in this paper. The compounds were separated and purified by repeated column chromatographic methods on silica gel and HPLC, and the chemical structures of compounds were determined by spectral data analyses. Twenty-nine compounds were obtained and identified as isoimperatorin (1), β-sitosterol (2), imperatorin (3), bergapten (4), osthenol (5), xanthotoxin (6), isoimpinellin (7), dehydrogeijerin (8), phellopterin (9), isodemethylfuropinarine (10), 7-demethylsuberosin (11), alloimperatorin (12), xanthotoxol (13), isooxypeucedanin (14), alloisoimperatorin (15), demethylfuropinarine (16), 5-hydroxy-8-methoxypsoralen (17), oxypeucedanin methanolate (18), pabulenol (19), byakangelicin (20), marmesin (21), (+) -decursinol (22), heraclenol (23), oxypeucedanin hydrate (24), marmesinin (25), ulopterol (26), erythro-guaiacylglycerol-β-ferulic acid ether (27), threo-guaiacylglycerol-β-ferulic acid ether (28), and uracil (29). Compounds 5, 8, 11, 18, 21-23, and 26-28 were obtained from the roots of title plant for the first time.
Angelica ; chemistry ; Coumarins ; chemistry ; isolation & purification ; Furocoumarins ; chemistry ; isolation & purification ; Methoxsalen ; chemistry ; isolation & purification ; Phytochemicals ; analysis ; chemistry ; Plant Roots ; chemistry

Protein tyrosine phosphatase (PTP) 1B is a potential target for the treatment of diabetes and obesity. We have previously identified the benzoyl sulfathiazole derivative II as a non-competitive PTP1B inhibitor with in vivo insulin sensitizing effects. Preliminary SAR study on this compound series has been carried out herein, and thirteen new compounds have been designed and synthesized. Among them, compound 10 exhibited potent inhibition against human recombinant PTP1B with the IC50 value of 3.97 micromol x L(-1), and is comparable to that of compound II.
Humans ; Protein Tyrosine Phosphatase, Non-Receptor Type 1 ; antagonists & inhibitors ; Structure-Activity Relationship ; Sulfathiazoles ; chemistry ; pharmacology

ObjectiveTo introduce the indications and operative procedure of anatomic reconstruction of the distal radioulnar ligaments in patients with chronic instability of the distal radioulnar joint(DRUJ),and report its preliminary clinical results.Methods From October 2008 to June 2009,6 patients with instability of the DRUJ underwent anatomical reconstruction using a free palmaris longus tendon graft,including 4 males and 2 females with an average age of 22 years.A 5 cm dorsal incision was made between the fifth and sixth extensor compartments.An L-shaped flap was created in the DRUJ capsule.This flap is then elevated proximally to expose the articular surface of the DRUJ and the proximal triangular fibular cartilage complex(TFCC).A tunnel was made through the radius.The other tunnel was made between the ulnar neck and the fovea of the ulnar head.A whole-length palmaris longus tendon graft was taken.The volar opening of the radius tunnel was exposed through a longitudinal incision radial to the flexor carpi ulnaris tendon.One end of the graft was pulled to the palmar side easily through the tunnel.A hemostat was penetrated through the volar capsule to the volar side proximal to the remaining TFCC.The end of the graft was grasped with the hemostat and pulled back along this tract.Both graft limbs were passed through the ulnar tunnel to exit at the ulnar neck.One limb of the tendon was passed around the ulnar neck and deep to the ECU sheath.With the forearm in neutral rotation,the limbs were pulled taut,tied together,and secured with sutures.Immobilize the extremity in a long-arm plaster splint with the forearm in neutral position for 4 weeks,and changed to a short arm cast for an additional four weeks.ResultsThe average follow-up period for all 6 patients was 14 months(range,9-24).No infection and sensory nerve branch disturbance occurred.The pain symptom was reduced and the grip force was improved significantly.A functional evaluation was performed using the modified Mayo wrist scoring system.All patients had better wrist scores postoperatively in the short (mean,95) term compared to preoperatively(mean,69).Five patients satisfied with the final result.Conclusion Anatomic reconstruction of the distal radioulnar ligaments is indicated for chronic DRUJ instability without osteoarthritis,it is a reliable method with a very good short term follow up result.Restoration of the radioulnar ligaments offers the best possibility to restore the normal DRUJ primary constraints and kinematics.

ObjectiveTo evaluate the relationship of human papillomavirus(HPV) intection with expressions of cell cycle regulatory proteins cyclin D1,E and their dependent kinase inhibitor p27 in bowenoid papulosis(BP).MethodsTissue specimens were obtained from the lesions of 44 patients with BP,and circumcised foreskin tissue from 10 males served as the control.Gene chip was used to determine the genotypes of HPV,and immunohistochemistry to quantify the expressions of cyclin D1,E,p27,in these specimens.Results Of the 44 BP specimens,all were positive for HPV DNA,38(86.36％) for high risk types of HPV,and 6 for low risk types of HPV.Of the high risk HPV-positive specimens,30(68.18％) harbored HPV16,16 harbored single HPV 16,14 harbored other types of HPV besides HPV 16,8 harbored other high risk types of HPV.HPV 6 predominated in low risk HPV-positive specimens.The expression of cyclin D1 was significantly higher in patients with high-risk HPV(u =53.00,P＜ 0.05),with both high and low risk HPV(u =5.00,P＜ 0.01) and with low risk HPV (u =22.50,P＜ 0.05) than in normal human controls,and higher in patients with both high and low risk HPV (u =44.00,P＜ 0.01) and with low risk HPV (u =22.50,P＜ 0.05) than those with high risk HPV.In the case of cyclin E expression,patients with high risk HPV (u =0.00,P ＜ 0.01 ),with both high and low risk HPV (u =4.00,P ＜ 0.01 ),and with low risk HPV(u =1.50,P ＜ 0.01 ) were higher than normal human controls,and patients with high risk HPV were higher than those with low risk HPV(u =11.00,P ＜ 0.01).No significant difference was observed in the expression of p27 between patients with high and low risk types of HPV.A significant increase was observed in the expression of p27 in patients aged ＞ 50 years compared with patients aged 20-30 years(u =47.00,P＜ 0.05) and aged 31-50 years (u =55.50,P＜ 0.05),as well as in the expression of cyclin E in patients aged ＞ 50 years compared with those aged 20-30 years(u =45.50,P ＜ 0.05),and in female patients compared with male patients (u =137.50,P＜ 0.05).ConlusionThere is a significant difference in the expression of cyclin D1,E and p27 among patients with BP infected with different types of HPV.

Objective To assess left ventricular(LV) longitudinal strain in patients with coronary heart disease by two-dimensional speckle tracking imaging (2DSTI),and to explore the clinical value of 2D longitudinal strain in detecting myocardial ischemia. Methods Forty-four patients with coronary heart disease (CHD group) and 28 age-matched subjects (control group) were enrolled into this study. The two-dimensional data were obtained in apical 4-chamble, 2-chamber and long axis view. And the longitudinal strains of every segments, the average longitudinal strain of LV 18 segments (SL18), the average longitudinal strain of 12 segments (SL12,excluded the 6 apical segments) were analyzed. Results In the patients with CHD, the longitudinal strain of ischemia segments and the global LV longitudinal strain were significantly decreased than that of the control subjects. Both in patients with CHD and in control subjects,the longitudinal strains in apical segments were higher than that of middle and basal segments. There was significant difference between SL18 and SL12 ( P=0.027 in CHD group and P =0.003 in control group).Receiver operating curve (ROC) analysis demonstrated that the cutoff point of SL18 to detect myocardial ischemia was - 18.8％ (sensitivity 80.2％ and specificity 74.1％ ) ,and the cutoff point of SL12 to detect myocardial ischemia was - 17.8％ ( sensitivity 81.7％ and specificity 85.6％ ). Conclusions 2D longitudinal strain was sensitive to detect myocardial ischemia, SL12 was better than SL18 in detecting myocardial ischemia. 2DSTI might be useful for identifying patients with severe CHD.