OBJECTIVE To investigate the effects and mechanism of luteolin on osteogenic repair of bone defects. METHODS The targets and potential pathways of luteolin in the treatment of bone defects were screened by network pharmacology method， and then the top 2 targets were selected by Hub gene screening for molecular docking verification， with binding energy as the evaluation standard. In vitro experiments were conducted on rat bone mesenchymal stem cells （BMSC） and rat umbilical vein endothelial cells （RUVEC）. Phenotypic validation was performed using alkaline phosphatase staining， alizarin red S staining， and in vitro angiogenesis experiments. Western blot assay was used to detect the protein expressions of phosphatidylinositol 3 kinase （PI3K） and protein kinase 1 （Akt1）， so as to validate the mechanism of luteolin on osteogenic differentiation of BMSC and angiogenesis of RUVEC in vitro. RESULTS The results of network pharmacology showed that the effects of luteolin on vascular formation and bone repair in bone defects were mainly related to Akt1， SRC， estrogen receptor 1， epidermal growth factor receptor， cyclooxygenase 2， matrix metalloproteinase 9 targets， and were closely related to PI3K-Akt signaling pathway. The results of molecular docking showed that luteolin binding to Akt1 and SRC proteins was stable. The results of in vitro experiments showed that luteolin could significantly improve the expressions and activities of alkaline phosphatase in BMSC， increased the number of calcium salt deposits and calcified nodules， and promoted calcification of BMSC. Compared with luteolin 0 μmol/L group， the angiogenesis ability of RUVEC was enhanced significantly in luteolin 1， 10 μmol/L groups， the length of blood vessels and the protein expressions of PI3K and Akt1 were significantly increased （P＜0.05 or P＜0.01）； the higherthe concentration， the better the effect. CONCLUSIONS Luteolin may play a role in promoting angiogenesis and bone repair at the fracture site by activating PI3K/Akt signaling pathway and promoting the protein expressions of PI3K and Akt1.

Objective To study the changes in intestinal structure and function of Parkinson's dis-ease(PD)model in cynomolgus monkeys so as to provide scientific basis for exploring the mecha-nism and intervention of constipation and other intestinal symptoms in PD patients.Methods Six male cynomolgus monkeys were subjected,and three of them received intracarotid injection of MPTP for manifestations of typical PD motor symptoms.The monkeys with the Kurlan score reached 10 and persisting for over 3 months without abrogation were identified as PD model(PD group).The other three monkeys served as control group.The brain and ileum tissue samples were collected from the two groups of monkeys.Immunohistochemical staining with tyrosine hydroxy-lase(TH)was used to determine the number of dopaminergic neurons in the substantia nigra of the brain and the changes in peripheral TH of the intestine.HE staining was employed to observe the structure of the intestine.Intestinal permeability was evaluated by atresia occlusive zone pro-tein 1(ZO-1),and intestinal peristalsis function was assessed with intestinal pacemaker cell bio-markers oncogene c-kit and protein gene product 9.5(PGP9.5).Results When compared with the control group,the PD group had significantly less number of nigrostriatal dopaminergic neurons in the left and right sides(133.13±108.63 vs 957.21±225.56,t=5.705,P=0.005;155.74±62.48 vs 917.52±161.14,t=7.611,P=0.002),lower expression of TH in the ileal intermuscular plexus(0.79±0.01 vs 0.73±0.01,t=5.149,P=0.007),reduced villus density with irregular arrange-ment,scattered structure,and detachment of goblet cells,and increased expression of ZO-1(0.28± 0.01 vs 0.22±0.02,P=0.006)and c-kit(0.21±0.01 vs 0.18±0.01,P=0.007)in the ileum muco-sa,but there was no such difference in the expression of PGP9.5 between the two groups(0.31± 0.08 vs 0.38±0.06,P=0.322).Conclusion Intestinal barrier integrity is damaged in PD mon-keys,with damaged villi,increased intestinal permeability and decreased peristalsis,and peristaltic function related intermuscular neurons are not involved.

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.

Purpose: Non-coding RNA activated by DNA damage (NORAD) has been reported to be a cancer-related long non-coding RNA (lncRNA) implicated in the progression of several cancers; however, its role in breast cancer (BC) has not yet been clarified. Methods: Quantitative real-time polymerase chain reaction was used to examine NORAD, microRNA (miR)-155-5p, and suppressor of cytokine signaling 1 (SOCS1) mRNA expression levels. Western blotting was used to analyze SOCS1 protein expression. The malignancy of BC cells was assessed using the cell counting kit-8 (CCK-8), BrdU, and Transwell assays.Bioinformatics analysis, RNA immunoprecipitation assay, and dual-luciferase reporter gene assays were used to verify the targeted relationship between NORAD and miR-155-5p.Additionally, the regulatory effects of NORAD and miR-155-5p on SOCS1 expression were determined by western blotting. Results: NORAD expression was significantly reduced in BC cell lines and tissues, and its low expression was associated with poor tumor tissue differentiation. NORAD overexpression repressed BC cell proliferation, migration, and invasion, whereas its knockdown produced the opposite effects. Additionally, miR-155-5p was found to be a target of NORAD, and the biological functions of miR-155-5p and NORAD were counteractive. MiR-155-5p was confirmed to target SOCS1, and SOCS1 was found to be positively regulated by NORAD. Conclusion NORAD suppresses miR-155-5p to upregulate SOCS1, thereby repressing the proliferation, migration, and invasion of BC cells.

Purpose: Non-coding RNA activated by DNA damage (NORAD) has been reported to be a cancer-related long non-coding RNA (lncRNA) implicated in the progression of several cancers; however, its role in breast cancer (BC) has not yet been clarified. Methods: Quantitative real-time polymerase chain reaction was used to examine NORAD, microRNA (miR)-155-5p, and suppressor of cytokine signaling 1 (SOCS1) mRNA expression levels. Western blotting was used to analyze SOCS1 protein expression. The malignancy of BC cells was assessed using the cell counting kit-8 (CCK-8), BrdU, and Transwell assays.Bioinformatics analysis, RNA immunoprecipitation assay, and dual-luciferase reporter gene assays were used to verify the targeted relationship between NORAD and miR-155-5p.Additionally, the regulatory effects of NORAD and miR-155-5p on SOCS1 expression were determined by western blotting. Results: NORAD expression was significantly reduced in BC cell lines and tissues, and its low expression was associated with poor tumor tissue differentiation. NORAD overexpression repressed BC cell proliferation, migration, and invasion, whereas its knockdown produced the opposite effects. Additionally, miR-155-5p was found to be a target of NORAD, and the biological functions of miR-155-5p and NORAD were counteractive. MiR-155-5p was confirmed to target SOCS1, and SOCS1 was found to be positively regulated by NORAD. Conclusion NORAD suppresses miR-155-5p to upregulate SOCS1, thereby repressing the proliferation, migration, and invasion of BC cells.

OBJECTIVE：To systematically evaluate therapeutic efficacy of Gongliuqing capsules combined with mifepristone in the treatment of uterine leiomyoma ，in order to provide evidence-based reference for clinical medication. METHODS ：Retrieved from Cochrane Library ，PubMed，Embase，CJFD，VIP，CBM and Wanfang database ，randomized controlled trials （RCTs）about Gongliuqing capsules combined with mifepristone （trial group ）versus mifepristone alone （control group ）in the treatment of uterine leiomyoma were collected. After literature screening and data extraction ，the quality of included literatures was evaluated with modified Jadad scale. Meta-analysis was conducted by using Stata 14.0 software，and trial sequential analysis （TSA）was performed by using TSA 0.9 software. RESULTS ：A total of 12 RCTs were included ，involving 1 210 patients. The results of Meta- analysis showed that the total response rate of trial group [RR ＝1.12，95％CI（1.00，1.26），P＜0.05] was significantly higher than that of control group ；maximum uterine leiomyoma volume after treatment [SMD ＝－1.08，95％CI（－1.21，－0.95），P＜0.05]，uterine volume after treatment [SMD ＝－0.80，95％CI（－1.14，－0.45）， P＜0.05]，follicle stimulating hormone （FSH）level [SMD ＝ － 0.28，95％ CI（－ 0.45，－ 0.19），P＜0.05]，luteinizing hormone（LH）level [SMD ＝－0.44，95％CI（－0.52，－0.12）， 020-38076311。E-mail：867203217@qq.com P＜0.05]，E2 level [SMD ＝－2.69，95％CI（－3.08，－1.49）， P＜0.05] and progesterone （P）level [SMD ＝－1.27，95％CI（－1.69，－0.71），P＜0.05] of trial group were significantly lower or better than those of control group. Results of subgroup analysis showed that except for the level of FSH in 5 and 10 mg mifepristone groups （P＞0.05），maximum uterine leiomyoma volume after treatment ，uterine volume after treatment ，the levels of FSH，LH，E2 and P in trial group were significantly lower than control group. The results of TSA showed that there were definite evidences for total response rate of Gongliuqing capsules combined with mifepristone being better in the treatment of hysteromyoma. CONCLUSIONS ：Total response rate of Gongliuqing capsules combined with mifepristone in the treatment of hysteromyoma is better than mifepristone alone ，which can effectively decrease the volume of maximum uterine leiomyoma volume and uterine vilume ，and reduce the level of serum hormone.

OBJECTIVE： To evaluate the literature quality of systematic reviews/Meta-analysis of oral administration of traditional Chinese medicine （TCM） in the treatment of lumbar disc herniation （LDH） using radar plot， and to provide scientific and effective evidence for clinical use of medicine. METHODS： Retrieving CNKI， VIP， Wanfang database， CBM， PubMed， Cochrane library and Embase during the establishement of database to Oct. 1st， 2018， the literatures about systematic reviews/Meta-analysis of oral administration of TCM in the treatment of LDH were collected. After data extraction of literatures met inclusion criteria， the quality literatures were evaluated from 6 aspects of radar plot （year of publication， design type， AMSTAR methodological quality evaluation， PRISMA reprot quality evaluation， homogeneous， publication bias risk）. The average score of rank number was calculated. Moreover， Excel 2010， Adobe Illustrator CC and other software were used to draw and optimize the radar plot. RESULTS： A total of 6 qualified literatures were included； average score of rank number of 6 aspects were 3.83， 4.67， 3.83， 3.67， 6.00， 4.67， scoring 4.56 in average. Multivariate evaluation of radar plot showed that 2 studies had higher qualities and only 1 study had lower qualities relatively. However， problems could be found such as information selection bias， inclusion and exclusion criteria， publication situation， limitations， project registration. CONCLUSIONS： The literature quality of systematic review/Meta-analysis of oral administration of TCM in the treatment of LDH need to be improved， starting with strengthening methodological quality and reporting quality. Radar plot is a visual and effective method of graphic evaluation， which is worth popularizing and applying in the future.

Objective To provide a method to modify accurately the Reverdin osteotomy template for hallux valgus using 3D reconstruction and printing.Methods From June 2015 to June 2016,11 patients (16 feet) with hallux valgus at our departments underwent weight-bearing X-ray examination and continuous spiral CT scanning of the feet.The outer turning angle of hallux averaged 33.50° ± 6.80°,the first intermetatarsal angle 12.20°± 2.90° and the distal metatarsal articular angle 15.20°± 2.60°.Their imaging Dicom data were imported into Materialise Mimics Innovation Suite v16.0 software for generation of 3D models of the pelvis which were then stored in stereolithography format and imported into Imageware 12 software.After optimal templates were reversely rebuilt to have the best angles and range for Reverdin osteotomy in the 3D models,they were manufactured by a rapid prototyping machine.The osteotomy templates were used in surgery to guide the osteotomy of hallux valgus.Correction of hallux valgus,bone union at the osteotomy sites and weight-bearing walk were observed postoperatively.Results Accurate angles of osteotomy were confirmed by postoperative radiography in all the 16 feet.Follow-ups for 6 to 12 months showed in the 16 feet a mean outer turning angle of hallux of 7.31 °±0.33° (from 5° to 11 °) and a mean correction of 21.92°± 4.8° (from 13° to 24°).Bone union was fine at the osteotomy sites and no pain was reported during weight-bearing walk.Conclusion 3D reconstruction and printing can produce a patient-specific template for accurate Reverdin osteotomy for hallux valgus,leading to increased contact area and fine union of the osteotomy ends.

Objective The purpose of this study was to determine the changes of expression of angiogenic factor mRNA in the spinal cord of rats with protruded intervertebral disc and the effects of electroacupuncture , and to analyze the role of electroacupuncture in the spinal microvascular angiogenesis .Method Eighteen healthy male Sprague-Dawley rats were divided randomly into 3 groups:the electroacupuncture group , model group and sham-operated group .The protruded intervertebral disc models were generated by the left lateral and ventral spinal cord compression at T 13 using a self-made silicon sheet.Only the rats in the first group were treated by electroacupuncture once a day for consecutive 7 days.Spinal cord tissue samples were taken from the compression site at 7 days after operation .The mRNA levels of Ang-1, Tie-1, Ang-2, Tie-2, VEGF, Flt-1, caspase-3 and Tsp-1 were determined by RT-PCR, and the pathological changes of the spinal cord was examined using HE staining .Results The rats in the electroacupuncture treated group showed significantly im-proved hind leg function , a relatively complete spinal cord structure , and a clear boundary between grey and white matters . The expression levels of Ang-1, Ang-2, Tie-1, Tie-2, capase-3 and Tsp-1 in the spinal cord tissues of the model group were significantly higher than those of sham-operated group ( P<0.01 ) , but the levels of VEGF and Flt-1 between those two groups showed no significant difference (P>0.05).The expression levels of Ang-2, Tie-1, Tie-2, caspase-3 and Tsp-1 of the electroacupuncture group were significantly lower than those in the model group (P<0.01), while the expression levels of Ang-1, VEGF and Flt-1 were not significantly different between the two groups (P>0.05).All the indexes be-tween electroacupuncture and sham-operated groups showed no significant difference ( P>0.05 ) .Conclusions Our re-sults demonstrate that mRNA expression of relevant angiogenic factors were abnormal after spinal cord compression , while electroacupuncture can down-regulate the expression of Ang-2, Tie-2,Tsp-1 and caspase-3, and modulate the promoting and inhibiting factors of angiogenesis to return towards normal , therefore , to create beneficial conditions for the repair of spinal cord injuries .

The study aims to investigate the effect of the ratio of long axis to short axis (RLS) of upright polypropylene infusion bag on discharging process and to search the best RLS. Aiming at five different RLS (1. 5 : 1, 2 : 1, 3 : 1, 4 : 1 and 5 : 1, respectively) with the volume of 100 mL, 250 mL and 500 mL, respectively, based on finite element method, analyzing the variation of stress distribution, emptying rate, drugging space and steadiness coefficient, etc. For the bags of the same volume, emptying rate increased with increasing of RLS, but the steadiness coefficient decreased with increasing of RLS. The specific increasing amplitude of emptying rate and decreasing range of steadiness coefficient were as follows: 20% and 49% for 100 mL infusion bag, 9% and 51% for 250 mL infusion bag, and 11% and 46% for 500 mL infusion bag, respectibvely, when RLS increased from 1. 5 : 1 to 5 : 1. Comparatively speaking, the increasing amplitude of the emptying rate is remarkably less than the decreasing range of the steadiness coefficient. By comprehensive consideration of both emptying rate and steadiness coefficient, lower RLS is recommended for upright polypropylene infusion bag.
Drug Delivery Systems ; instrumentation ; Finite Element Analysis ; Polypropylenes