OBJECTIVETo investigate the mechanism of Yanshu Injection (YI) for overcoming multidrug resistance in breast carcinoma MCF-7 cells.

METHODSHuman breast carcinoma MCF-7 cells and doxorubicin-resistant MCF-7/DOX cells were treated with YI. Its inhibition on the cell proliferation was detected by MTT assay. The fluorescence intensity of doxorubicin was detected by flow cytometry. The expression of apoptosis related protein and P-glycoprotein were examined by immunoblotting after treated by YI.

RESULTSThe inhibitory action of YI on MCF-7/DOX cells was similar to that of MCF-7 cells, indicating no cross resistance (P > 0.05). 1/16 YI could obviously induce the apoptosis of MCF-7 cells and DOX cells. 1/256 YI +5 nmol/L doxorubicin and 1/128 YI +5 nmol/L doxorubicin could reduce the survival rate of MCF-7/ DOX resistant cells from 86.8% to 74.6% (P < 0.05) and 71.6% (P < 0.01) respectively, showing obvious synergistic effect. Besides, the accumulation of doxorubicin was increased after treated by YI in the MCF-7/ DOX cells. Results of immunoblotting indicated that reduction of P-glycoprotein expression was detected in MCF-7/DOX cells after exposure to YI.

CONCLUSIONYI could overcome the multidrug resistance in breast carcinoma MCF-7 cells possibly through reducing the expression of P-glycoprotein.

Apoptosis ; drug effects ; Cell Proliferation ; drug effects ; Drug Resistance, Multiple ; drug effects ; Drug Resistance, Neoplasm ; drug effects ; Drugs, Chinese Herbal ; pharmacology ; Female ; Humans ; MCF-7 Cells

Objective To investigate the accuracy of analgesia/nociception index (ANI) in assessing the severity of postoperative pain in patients.Methods Eighty patients,aged 21-77 yr,of American Society of Anesthesiologists physical status Ⅰ-Ⅲ,scheduled for elective operation,were admitted to the postanesthesia care unit after the patients were extubated at the end of operation,and ANI was monitored.Immediately after admission to the postanesthesia care unit (T0),numerical rating scale (NRS) score was recorded.If NRS score was 0-3,the patients received no treatment,and NRS score was recorded again 10 min later (T1).If NRS score was 4-10,fentanyl 50 μg was injected intravenously,and NRS score was recorded again 5 min later (T2).ANI value was recorded at T0,T1 and T2.NRS score was considered as the criterion for assessment of the severity of pain.The receiver operating characteristic curve was used to analyze the sensitivity and specificity of ANI in determining NRS scores,the cut-off value was determined,and the area under the curve and 95％ confidence interval were calculated.Pearson correlation was used to analyze the correlation between ANI and NRS score.Results The area under the curve (95％ confidence interval) of ANI in determining NRS scores was 0.873 (0.816-0.929),and the cut-off value was 45 with a sensitivity of 74.8％ and a specificity of 87.5％.ANI was negatively correlated with NRS score,and the correlation coefficient was-0.705 (P＜0.05).Conclusion ANI provides high accuracy in assessing the severity of postoperative pain with a cut-off value of 45 in the patients.

OBJECTIVETo explore the scavenging action of tenuigenin (TEN) on intracerebral amyloid β protein (Aβ) aggregation and the abnormal phosphorylated tau protein and its mechanism in Alzheimer's disease (AD) rats' brain.

METHODSAβ1-40 was injected into the right CA1 region hippocampus to establish the AD model. Successfully modeled rats were divided into the model group, the low, middle, high TEN group. Rats were administered with TEN (18.5, 37.0, 74.0 mg/kg) by gastrogavage. Besides, a sham-operation group was set up. Expression levels of Aβ1-40 and Tau p-Ser262 were detected by immunohistochemistry. Expression levels of ubiquitin (Ub) and Ub-protein ligase E3 were measured by Western blotting.The content of 26S proteasome was detected by ELISA.

RESULTSImmunohistochemical results showed that the number of Aβ and Tau p-Ser262 positively reacted neurons significantly increased in model group, when compared with the sham-operation group (P < 0.01). Results of Western blot showed expression levels of ubiquitinated protein were up-regulated and those of Ub-protein ligase E3 were down-regulated in the model group (P < 0.01). ELISA results showed that the content of 26S proteasome significantly decreased in AD rats' brain (P < 0.01). Compared with the model group, expression levels of Aβ1-40, Tau p-Ser262, and Ub significantly decreased; expression levels of Ub-protein ligase E3 apparently increased; the content of 26S proteasome significantly increased in each TEN treatment group (P < 0.05, P < 0.01). Best effect was shown in 37.0 mg/kg and 74.0 mg/kg TEN groups.

CONCLUSIONSUb proteasome pathway (UPP) participated in the occurrence of AD. TEN could obviously reduce intracere- bral Aβ1-40 accumulation and abnormal tau phosphorylation.

Alzheimer Disease ; metabolism ; Amyloid beta-Peptides ; Animals ; Drugs, Chinese Herbal ; pharmacology ; Hippocampus ; metabolism ; Neurons ; metabolism ; Phosphorylation ; Proteasome Endopeptidase Complex ; metabolism ; Rats ; Ubiquitin-Protein Ligases ; metabolism ; Ubiquitins

BackgroundPosterior capsule opacification(PCO) is the main cause inducing low vision after extacapsular cataract extraction. Our previous study determined that polylysine-ethylene diamine tetraacetic acid (EDTA) (PLE) can suppress the incidence of PCO. ObjectiveThe goal of this experiment was to investigate the inhibition of polylysine-EDTA on rabbit lens epithelial cells (LECs)proliferation in vitro and the effective concentrations of polylysine-EDTA. MethodsThe anterior capsular membranes from 10 3-month-old clean New Zealand white rabbits were digested and then cultured to obtain the LECs. The second and third generation of LECs were inoculated on the 96-hole culture plate with the cell density of the 1 × 105/ml. 12.5,25.0,50. 0,100. 0 μmol/Lof PLE were added into the culture medium for 48 hours respectively,and the DMSO medium was used at the same way as the control group. The proliferation of the LECs was then detected by MTT method and the inhibitory rate of PLE on LECs growth was calculated. ResultsLECs grew at a near normal state in ≤25.0 μmol/L PLE groups,however,cultured LECs were out of shape and the numbers decreased with the weakened adhesion ability in ≥50.0 μ mol/L PLE groups. The A490 values of LECs were 0. 278±0. 013,0. 266±0. 028,0. 260±0. 022 and 0. 247±0. 012 in 12. 5,25.0,50. 0, 100. 0 μmol/L polylysine-EDTA groups respectively and were lower than 0. 311 ±0. 038 of DMSO control group( P=0. 035,0. 011,0. 009,0.013 ). The inhibitory rates of 12. 5,25.0,50. 0, 100.0 μmoL/L PLE on LECs proliferation were 10.61％ , 14.47％ , 16.40％ and 20. 58％ respectively. ConclusionsPolylysine-EDTA can inhibit the growth and proliferation of LECs in vitro at a dose-dependent manner.

Wnt/β-catenin signaling pathway plays an important role in the proliferation, growth, invasion, and metastasis of human cancers. Moreover, β-catenin/T-cell factor 4 (TCF4) interaction regulates the transcription of the key oncogenes in Wnt/β-catenin signaling pathway. Therefore, β-catenin/TCF4 interaction would be a promising therapeutic target for the development of highly selective anticancer agents. At present, most ongoing small-molecule inhibitors targeting β-catenin/TCF4 interaction, including PKF222-815, iCRT3/5/14, LF3, and sanguinarine, have been developed in preclinical studies for human cancer therapeutics. In this review, we summarized the research advances of up-to date inhibitors targeting β-catenin/TCF4 interaction, including the molecular structure and cellular functions of β-catenin in canonical Wnt signaling pathway. This review holds a hopeful avenue for the development of novel and highly selective Wnt inhibitors targeting β-catenin/TCF4 interaction for future anticancer strategy.

Most rotational and angulational variations in young children are benign and resolved spontaneously. However, they may cause great concerns to parents. In order to provide a deliberate assessment and management of lower limb rotational and angulational problems, it is necessary for pediatricians to understand the normal variations of lower limb development in healthy children combined with the features of child growth and development and detail physical examinations.
Humans ; Lower Extremity ; embryology ; Lower Extremity Deformities, Congenital ; diagnosis ; therapy ; Rotation

Objective To observe the reactivity of pupillary diameter variation responding to numerical rating scale on postoperative pain to explore the accuracy of pupillary diameter variation for pain assessment.Methods Eighty patients after selected surgery (male 43 cases,female 37 cases,aged 24-79 years,ASA gradeⅠorⅡ)were included for the trial.After endotracheal extubation and on arri-val in the post-anaesthesia care unit (PACU),the levels of pain on numerical rating scale (NRS)were rated and recorded subsequently.If NRS was within 0-3,no analgesic was administered and 50 μg fentanyl was administrated after 5 min if NRS rated in 4-10.The pupillary diameter (PD),systolic blood pressure (SBP)and heart rate (HR)were recorded every minute during 20 minute after first NRS evaluation,the corresponding maximum variation of above index were calculated simultaneously in 10 minutes with NRS 0-3,after 5 minutes with NRS 0-3 to 4-10,after 5 minutes with NRS 4-10 to 0-3,in 10 minutes with NRS 4-10 which were marked respectively with ΔPD,ΔSBP and ΔHR.With the variation of NRS as a criterion,the reactivity of ΔHR,ΔSBP and ΔPD responding to NRS varia-tion were assessed by analysing the receiver operating characteristic curve (ROC),the area under the receiver operating characteristic curve (AUC)was calculated.Results The patients' ROC value ofΔHR,ΔSBP and ΔPD responding to NRS variation were AUCΔPD 0.904 (95% CI 0.822-0.987 ), AUCΔSBP 0.65 1(95%CI 0.5 10-0.781)and AUCΔHR 0.588(95%CI 0.444-0.733)respectively.Value of AUCΔPD was larger than that of AUCΔSBP and AUCΔHR respectively (P < 0.05 ).Importantly, operating characteristic curve (ROC)analysis showed that the diagnostic cutoff value of ΔPD was 41.3% with a sensitivity of 80.0% and a specificity of 93.5% and the diagnostic cutoff value of ΔSBP was 10.3% with a sensitivity of 62.4% and a specificity of 71.5%.Conclusion This study demon-strated that the accuracy of ΔPD was higher than ΔSBP and ΔHR responding to pain/analgesia evalu-ation.ΔPD was a valuable index for assessment of postoperative pain.

Objective To observe the effect of S-adenosyl-L-methionine(SAMe) in treatment of jaundice in newborns and its mechanism.Methods Two hundred and two newborn infants with jaundice were treated with SAMe,76 cases in control group treated with phototherapy and liver enzyme induction elixir;SAMe 30-60 mg/(kg?d) were added to 202 cases intravenously in treatment group.The total biliorubin(T-BILI),direct bilinrubin(D-BILI) and indirect bilinrubin(I-BILI) were dynamically detected.Results Six days after treatment,the skin jaundice index in treatment group decreased remarkably.T-BILI,D-BILI and I-BILI decreased significantly.The curing effectiveness was higher in treatment group than that in control group.The number of applicating blood products and albumin,and blood produets/albumin were decreased in treatment group than those in control group.In those who used glucose to dissolve the SAMe 2.68% had blood-vessel phlebitis.Conclusions SAMe can efficiently quicken the retrogression of jaundice in newborns.It can reduce the use of blood products.It is a reliable and safe drug to treat jaundice in newborns.

Based on the gene sequence of AIV matrix protein 2(M2) and two cytotoxic T-lymphocyte epitopes derived from nucleoprotein,the prokaryotic expression vector pET-3M2e-NP1-NP2 was constructed.The target gene was expressed in the solvable form in BL21(DE3) when induced with 1.0 mmol/L IPTG and Western blot analysis showed that the expression product had good immunogencity.Purified fusion protein was mixed with various amount of adjuvant,including Freund's,Vash oil and chitosan,and then immunized 20-day-old chicken by intramuscular injection and boosted 3weeks later.Blood samples were collected weekly following the primary vaccination.The anti-M2e antibody was detected with ELISA method with the synthesized peptide as coated antigen;the neutralizing ability of anti-serum was evaluated on MDCK cell line and chick embryo,the CD4+ and CD8+ T lymphocyte amounts in peripheral blood of immunized chicken was measured by flow cytometry.Results showed that the fusion protein can induce immunological reaction,and the antibody can bind with the viral M2 protein that expressed on the surface of MDCK cells.Flow cytometry result showed that CD4+ and CD8+ T lymphocyte in peripheral blood increased obviously following immunization(P

Objective To observe the long term effects of arthroscopic knee debridement and reconstructing operation for treating osteoarthritis in patients with Kaschin-Beck disease. Methods Thirty-one cases of patients with Kaschin-Beck disease were followed for 6 years after operation of articular clearing by arthroscope. Index of pain, symptoms of self-evaluation, range of motion, walking distance, standing test by affected leg when bending at 30° or 60° were recorded and compared with the preoperative results. Results Twenty-four cases were followed up for 6 years. Six years after operation the pain index(3.38 ± 2.87) was dramatically decreased compared to that before operation (6.88 ± 1.45, t = 5.30, P ＜ 0.05). Patients symptoms markedly improved by subjective self-evaluation was 70.83% (17/24), the effective rate was 100% (24/24). The number of cases that could stand up when leg bending at 30° or 60° were 21,18 cases, respectively, compared with that of preoperative of 14, 11 cases, respectively, the difference was statistically significant(x2 = 5.17,4.27, all P ＜ 0.05). Six years after operation the walking distance(3 cases ＜ 1 km, 11 cases 1 - 5 km and 10 cases ＞ 5 km) were greatly improved compared to the results before operation (12 cases ＜ 1 km, 9 cases 1 - 5 km and 3 cases ＞ 5 km, U = 2.88, P ＜0.05). Six years after operation the knee activity[(132.25 ± 14.52)°] remained at the same level, compared with that of preoperative [(131 .58 ± 14.68) °], the difference was not statistically significant (t = 0.16, P ＞ 0.05) .Conclusions The method of arthroscopic joint debridement to cure Kaschin-Beck disease knee osteoarthritis can significantly reduce pain, improve function and walking distance, with more stable long-term satisfactory outcome.