Objective:To investigate the mechanism of histone deacetylase (HDAC) inhibitor in down-regulating the expression of HER-2 in breast cancer cells and to provide an innovative therapeutic option to overcome the disadvantages of anti-HER-2 therapy. Meth-ods:HER-2-positive breast cell lines were treated with HDAC inhibitors. The changes in the gene and protein levels of HER-2 were de-tected by qPCR and Western blot. MiRNA microarray was used to identify the HDAC inhibitors, whereas qPCR was used to verify the miRNA expression. Results:In vitro cell experiments confirmed that the HDAC inhibitors TSA and SAHA can down-regulate the expres-sion of HER-2 in breast cancer cell lines. TSA can down-regulate the expression of HER-2 gene in BT474 and decrease the concentra-tions of 100 nmol by 10.7%and 200 nmol by 38.9%(P<0.05). TSA had no effect on the primary cells. The expression of HER-2 gene of BT474 was down-regulated by 93.9%(P<0.05) in the 5μmol/L group but not in the 1μmol/L group. SAHA significantly affected the pri-mary cells at a concentration of 1μmol/L and reduced the cells at 87.1%at a concentration of 5μmol/L. Seven miRNAs were identified from the miRNA microarray. MiR-762 was used as a basis to identify the changes in miRNA. The miRNA sputum identified by miRNA microarray and qPCR may be associated with the down-regulation of HER-2 by HDAC inhibitors. Conclusion: HDAC inhibitors may down-regulate the expression of HER-2 in breast cancer cells by changing some miRNAs.

Objective To investigate MRI characteristics of subacute combined degeneration(SCD)with secondary spinal canal stenosis.Methods The clinical and MRI imaging data of 56 patients with SCD were collected to analyze the performance characteristics between spinal cord lesions and spinal canal stenosis,which depended on the synergism of lumbar disc bluge or herniation,degenerative thickening of the ligament flavum and posterior longitudinal ligament.Results Among 56 SCD cases underwent MRI scan,45 cases were combined with spinal cord lesions which showed typical signs of SCD.37 patients were secondary spinal canal stenosis with typical signs,but 2 showed no typical signs.8 patients were no secondary spinal canal stenosis and showed typical.9 cases showed neither spinal cord lesions nor secondary spinal canal stenosis.There was significant difference (P <0.05)between relative secondary spinal canal stenosis and spinal anomaly signal.The course of 1 5 cases were shortened after treated by physical in 37 cases of SCD with secondary spinal canal. Conclusion The secondary spinal canal stenosis can cause microcirculation dysfunction of the spinal cord,which is a key factor contributing to the imaging manifestation.

Objective:To investigate the influence of joint line alteration on the mid-term clinical effects of primary medial pivot total knee arthroplasty (MP-TKA).Methods:Data of a total 189 patients (233 knees) with 30 males (30 knees) and 159 females (203 knees) with age 66.42±6.12, diagnosed as knee osteoarthritis and underwent primary MP-TKA from January to December 2015, were retrospectively analyzed. All cases were followed up for at least 4 years. The patients were divided into four groups according to the extent of alteration, namely <-4 mm, -4- mm, 0- mm and >4 mm. Range of motion (ROM), Knee Society's Knee Scoring System (KSS), the Western Ontario and McMaster University (WOMAC) osteoarthritis index score were compared preoperatively and at 4 years postoperatively.Results:The postoperative follow-up duration was 52.20± 2.94 months (48-59 months). A total of 133 knee (57%) had joint line raised and 100 cases (43%) joint line distal shifted. The overall height of joint line before surgery was 16.56±3.54 mm (7.33-25.32 mm) and 17.34±2.92 mm (7.25-25.43 mm) postoperatively. The average alteration was 0.78±3.17 mm (-6.00-9.91 mm) with statistically significant difference ( t=-2.596, P=0.010). There was no statistical difference among the four groups in terms of gender, body mass index, pre-operative tibia slope and post condylar offset. The overall preoperative ROM of the all groups was 90.45°±20.44°, which increased from baseline to 108.95°±12.55° at 4 years postoperatively ( t=-22.381, P<0.001). There was statistical difference in term of ROM among each group ( F=7.101, P<0.001). The ROM in group 0- mm and >4 mm was significantly higher than that in group <-4 mm and -4- mm ( P<0.05). The KSS function score and clinic score at 4 years postoperatively were significantly higher that those before surgery, the WOMAC score was statistically lower at 4 years postoperatively ( F=0.723, P<0.001; F=1.138, P<0.001; F=2.502, P<0.001). There was no significant difference among the four groups in terms of KSS score and WOMAC ( P>0.05). One case in >4 mm group had gasket prolapse at 6 month after surgery and 3 cases with immediate anterior knee pain occurred in <-4 mm group. Conclusion:MP-TKA can lead to significant joint line alteration. The overall ROM after surgery is positively correlated with the quantity of joint line alteration. However, there was no correlation between quantity of joint line alteration and the joint function scores. Thus, MP-TKA can achieve good mid-term clinical effects.

OBJECTIVE： To study the effects of Tiaopi huxin prescription （TPHXP） on the atherosclerosis （AS） of ApoE－/－ mice， and to investigate its mechanism. METHODS： Forty male ApoE－/－ mice were divided into blank group， model group， simvastatin group （positive control， 5 mg/kg） and TPHXP low-dose and high-dose groups （50， 150 mg/kg）， with 8 mice in each group. Except that blank group was given common diet， other groups were given high-lipid diet to induce AS model. After modeling， administration groups were given relevant medicine intragastrically， and blank group and model group were given constant volume of normal saline intragastrically， once a day， for consecutive 12 weeks. After last medication， the serum levels of TC， TG， LDL-C and HDL-C were determined by spectrophotometry. The serum level of NO was detected by nitrate reduction method. The serum levels of IL-6 and VCAM-1 were determined by ELISA. After separating thoracic aorta， HE staining was used to observe the formation of plaque in the thoracic aorta of mice in each group， and the corrected plaque area was calculated. Western blotting was conducted to determine the expression of NF-κB p65， Cav-1 and eNOS. RESULTS： Compared with blank group， the serum levels of TC， TG， LDL-C， IL-6 and VCAM-1 were increased significantly in model group， while the levels of HDL-C and NO were decreased significantly （P＜0.01）. The plaque of thoracic aorta was obvious and the corrected plaque area were increased significantly （P＜0.01）. The relative expression of NF-κB p65 and Cav-1 were increased significantly， while the relative expression of eNOS was decreased significantly （P＜0.01）. Compared with model group， the serum levels of TC， TG and LDL-C in administration groups， the serum levels of IL-6 and VCAM-1 in simvastatin group and TPHXP high-dose group were decreased significantly， while the serum levels of HDL-C and NO were increased significantly in administration groups （P＜0.05 or P＜0.01）. In administration groups， the plaques of thoracic aorta were reduced and the corrected plaque area was decreased significantly （P＜0.05 or P＜0.01）； the relative expression of NF-κB p65 and Cav-1 were decreased significantly， while the relative expression of eNOS was increased significantly （P＜0.05 or P＜0.01）. CONCLUSIONS： TPHXP can regulate the level of blood lipid， decrease the level of inflammatory factors and inhibit the formation of AS plaque， the mechanism of which may be associated with inhibiting Cav-1/NF-κB pathway.

OBJECTIVE To prepare hyperoside mixed nanomicelles （Hyp-F127/TPGS） and optimize its preparation technology，and to investigate its intestinal absorption characteristics. METHODS Hyp-F127/TPGS was prepared by thin film dispersion method. Based on single factor test and Plackett-Burman design ，combined with Box-Behnken response surface method ， the preparation process was optimized and validated using entrapped efficiency （EE）and drug loading （DL）as evaluation indexes ， F127-TPGS mass ratio ，hydration time and the amount of Hyp as factors. The appearance and microscopic morphology of Hyp-F127/TPGS obtained by the optimal technology were observed ，and the particle size ，polydispersity index （PDI）and Zeta potential were also determined. The critical micelle concentration （CMC）of blank micelle （F127/TPGS），in vitro release behavior and preliminary stability of Hyp-F 127/TPGS were investigated ，and absorption characteristics of Hyp-F 127/TPGS were investigated by in situ unidirectional intestinal perfusion model. RESULTS The optimal preparation technology of Hyp-F 127/TPGS included F127-TPGS mass ratio of 2∶1，hydration time of 2 h，and Hyp amount of 9 mg. Results of three validation tests showed that the EE of Hyp-F 127/TPGS was （87.20±0.99）％，and the DL was （5.02±1.20）％，deviations from predicted values were 0.92％ and 2.39％. The micelles prepared by optimal technology were yellow ，clear and transparent solution ，with good Tyndall effect ；under transmission electron microscope ，they were spherical ，complete and evenly distributed ；the particle size was （15.02±0.16）nm， the PDI was 0.092±0.031，and the Zeta potential was （－6.67±1.47）mV. The CMC of F 127/TPGS was 21 μg/mL，Hyp-F127/ TPGS was stable after 4 weeks of storage at 4 ℃，and the cumulative release rates of Hyp-F 127/TPGS and Hyp control were （66.30±2.93）％（96 h）and（99.24±0.27）％（60 h），respectively. Hyp-F 127/TPGS and Hyp reference were absorbed in each intestinal segment ，and the main absorption sites were jejunum and duodenum respectively ；drug absorption rate constant andapparent absorption coefficient of the former were significantly higher than those of the latter （P＜0.05 or P＜0.01）. E-mail：zhangyuhangxz@163.com CONCLUSIONS The optimized preparation technology of Hyp-F127/TPGS is stable and feasible ；prepared Hyp-F 127/ TPGS shows a sustained -release effect ，which promotes the intestinal absorption of H yp to a certain extent.

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and is the fourth-leading cause of cancer-related deaths worldwide. HCC is refractory to many standard cancer treatments and the prognosis is often poor, highlighting a pressing need to identify biomarkers of aggressiveness and potential targets for future treatments. Kinesin family member 2C (KIF2C) is reported to be highly expressed in several human tumors. Nevertheless, the molecular mechanisms underlying the role of KIF2C in tumor development and progression have not been investigated. In this study, we found that KIF2C expression was significantly upregulated in HCC, and that KIF2C up-regulation was associated with a poor prognosis. Utilizing both gain and loss of function assays, we showed that KIF2C promoted HCC cell proliferation, migration, invasion, and metastasis both in vitro and in vivo. Mechanistically, we identified TBC1D7 as a binding partner of KIF2C, and this interaction disrupts the formation of the TSC complex, resulting in the enhancement of mammalian target of rapamycin complex1 (mTORC1) signal transduction. Additionally, we found that KIF2C is a direct target of the Wnt/β-catenin pathway, and acts as a key factor in mediating the crosstalk between Wnt/β-catenin and mTORC1 signaling. Thus, the results of our study establish a link between Wnt/β-catenin and mTORC1 signaling, which highlights the potential of KIF2C as a therapeutic target for the treatment of HCC.
Adult ; Aged ; Animals ; Carcinoma, Hepatocellular/pathology* ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Epithelial-Mesenchymal Transition/genetics* ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism* ; Kinesins/metabolism* ; Liver Neoplasms/pathology* ; Male ; Mice ; Mice, Inbred BALB C ; Middle Aged ; Neoplasm Staging ; Prognosis ; Protein Binding ; RNA, Small Interfering/metabolism* ; Survival Analysis ; Tumor Burden ; Wnt Signaling Pathway ; Xenograft Model Antitumor Assays ; beta Catenin/metabolism*