Objective : To investigate the activation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway molecules during the process by which kaempferol (Kae) promotes osteogenic differentiation of mouse bone marrow mesenchymal cells (BMMCs) under cyclic and uniaxial tension. Methods : BMMCs isolated and cultured in vitro were subjected to uniaxial dynamic tension with a 10% shape variable. The appropriate concentration of Kae was selected by cytotoxicity testing. The endogenous mTOR signal was inhibited by pp242. Four hours after traction, alkaline phosphatase (ALP) and osteocalcin (OCN) were detected by chemical colorimetry and ELISA, and the relative concentration of intracellular calcium was detected by flow cytometry. Phosphorylation of mTOR, 4E/BP1, and ribosomal protein S6 kinases (S6K), which are the main molecules of the endogenous mTORC1 signaling pathway, and expression of osteogenic transcription factors (Runx2 and Osterix) were detected by western blotting (WB), and mRNA expression levels of the above factors were detected by qRT-PCR. Results : The cytotoxicity test showed that 10 μmol/L Kae had little inhibitory effect on cell proliferation but had the strongest osteogenic ability. Four hours after stretching, Kae effectively promoted the osteogenic differentiation of BMMCs. The expression of ALP was （153.04 ± 18.72） U/mg, the expression of OCN was （1.64 ± 0.25） U. The mRNA and protein levels of Runx2 and Osterix were upregulated, and the intracellular calcium content was decreased. The mRNA and protein phosphorylation of mTOR and S6K was upregulated, and the opposite effect was observed with 4E/BP1. After pp242 was added to inhibit mTOR signaling, mTOR and S6K mRNA and protein phosphorylation were downregulated, but 4E/BP1 mRNA and protein phosphorylation was upregulated. The osteogenic differentiation of BMMCs was also significantly inhibited, mRNA and protein expression of Runx2 and Osterix were significantly downregulated, ALP and OCN expression were downregulated, and intracellular calcium content was increased. Conclusion Kae promotes osteogenic differentiation of mouse BMMCs under uniaxial dynamic tension through the mTORC1 signaling pathway.

Nanocrystals are nanoscale (1-1000 nm) dispersion systems in which small numbers of surfactants or polymers are used as stabilizers to disperse insoluble drug particles in water or oil. Nanocrystals enjoy not only high drug content, but also a simple and mature preparation process. At present, 24 nanocrystals products that have been marketed mainly focus on enhancing the solubility and bioavailability of poorly soluble drugs. And recent years have witnessed an increasing number of research reports on target drug delivery of nanocrystals through particle size control and surface modification. This paper mainly introduces three targeting strategies for prolonging the in vivo circulation time of nanocrystals, increasing the affinity for tumor cells and achieving the response to internal and external stimuli, and discusses the current challenges in the application of nanocrystal technology to targeted anti-tumor drugs.

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 investigate the expression of the mTORC1 signaling pathway during the osteogenic differentiation of mouse bone marrow mesenchymal cells (BMMSCs) under cyclic uniaxial tension and explore its possible role. Methods : The BMMSCs of mice were affected by uniaxial dynamic tensile force. Western blot was used to detect the expression changes of major molecules (mTOR, Raptor, S6K) in the endogenous mTORC1 signaling pathway at 0, 1, 2, 4, and 8 hours after stretching. Chemical colorimetry, ELISA and PCR were used to detect alkaline phosphatase (ALP), osteocalcin (OCN) and Runx2 mRNA, respectively. Then, inhibition, activation and control groups were established by administration of the drugs PP242, MHY1485 and PBS, respectively. Two hours after the stress, the expression of S6K was detected by western blot, and the expression of the osteogenic signal was continuously detected by the above methods. Results : Western blot analysis showed that the main molecules of the mTORC1 signaling pathway were all expressed within 8 hours after traction, and the highest expression was 2 hours after the stress. Compared with those in the control group, the ALP activity and OCN expression decreased and the Runx2 mRNA levels increased after the mTORC1 signal pathway was inhibited (P ＜ 0.001); ALP activity and OCN expression increased after the mTORC1 signal pathway was activated, while the Runx2 mRNA levels decreased (P ＜ 0.001). Conclusion The mTORC1 signaling pathway participates in the osteogenic differentiation of mouse BMMSCs under tension. The osteogenesis of BMMSCs under cyclic uniaxial tension would be enhanced if the mTORC1 signaling pathway was activated.

Objective : To explore the promoting effect of periostin on rapid distraction osteogenesis of the rabbit mandible and provide experimental evidence for the clinical use of periostin to promote osteogenesis. Methods: Twenty-four New Zealand male white rabbits underwent distraction osteogenesis, and after 3 days of retention, they were rapidly stretched at a stretch rate of 2 mm/d (total 5 d). The animals were randomly divided into group A and group B (12 per group). On the last day of the stretch, 0.5 mL of normal saline containing 40 μg of recombinant periostin was given to group B or an equal volume of normal saline was added to the control group (group A) for 8 days. At 4 weeks and 8 weeks post-stretch, 8 animals were randomly selected from each group to undergo a CT scan under general anesthesia. The bone mineral density and bone mineral content were detected by dual energy X-ray absorptiometry. Eight weeks post-stretch, all of the experimental animals were sacrificed. Six animals were randomly selected from each group for micro-CT and a histological examination, and the remaining animals were subjected to biomechanical tests. Results : CT images showed that the new bone formation in the distraction space of group B was significantly better than that of group A at 4 and 8 weeks post-stretch. At 4 weeks and 8 weeks post-stretch, the bone mineral density in group B was (0.157 ± 0.016) g/cm 2 and (0.234 ± 0.023) g/cm 2, respectively, and the bone mineral content was (0.096 ± 0.010) g and (0.204 ± 0.017) g, respectively. The above four means were significantly higher in group B than in group A (P < 0.001). The micro-CT images and data suggest that the stretch gap microstructure of group B has more mature features. Histological experiments showed that the trabecular bone of group B was thick and mature, with few chondrocytes. The biomechanical test results showed that the biomechanical strength of the distraction gap in group B was (228.47 ± 39.98) N, which was 1.24 times that of group A (P = 0.045). Conclusion Interstitial use of periosteal protein in the distraction space of the mandible in rabbits can promote local new bone formation and mineralization.

OBJECTIVE： To systematically evaluate the difference of therapeutic efficacy of Xianling gubao capsules combined with routine therapy for postmenopausal osteoporosis （PMOP）. METHODS： Retrieved from Cochrane Library， PubMed， Embase， ClinicalTrials， CNKI， VIP， Wanfang database and CBM， clinical randomized controlled trials （RCTs） about Xianling gubao capsules combined with placebo and routine treatment （trial group） versus placebo and routine treatment or Xianling gubao capsules （control group） alone in the treatment of PMOP were collected. After literature screening and data extraction， the quality of included literatures were evaluated with Cochrane system evaluator manual 5.3 recommend bias risk evaluation tool. Bayesian Network Meta-analysis was performed with Stata 14.0 software  and Bayesian Markov Chain Monte Carlo. RESULTS： A total of 16 RCTs were included， involving a total of 1 360 patients and 3 intervention measures as Xianling gubao capsules alone， Xianling gubao capsules combined with routine treatment， routine treatment. Results of Meta-analysis showed that in respect of improving total response rate， compared with routine treatment， Xianling gubao capsules combined with routine treatment [OR＝0.28，95％CI（0.12， 0.64），P＜0.05]could significantly improve total response rate； network Meta-analysis ranking showed that Xianling gubao capsules combined with routine treatment＞Xianling gubao capsules alone＞routine treatment. In terms of increasing bone mineral density （BMD）， compared with routine treatment， Xianling gubao capsules combined with routine treatment [OR＝0.45，95％CI（0.24， 0.84），P＜0.05] and Xianling gubao capsules alone [OR＝0.78， 95％CI（0.32， 0.84），P＜0.05] could significantly improve BMD； network Meta-analysis ranking showed that Xianling gubao capsules combined with routine treatment＞Xianling gubao capsules alone＞routine treatment. In the term of improving serum calcium level， compared with Xianling gubao capsules alone [OR＝4.76，95％CI（2.14， 10.59），P＜0.05] and routine treatment [OR＝0.45， 95％CI（0.21， 0.99），P＜0.05]， Xianling gubao capsules combined with routine treatment could significantly improve serum calcium level； network Meta-analysis ranking showed that Xianling gubao capsules combined with routine treatment＞routine treatment＞Xianling gubao capsules alone. In the term of improving serum phosphorus level， compared with Xianling gubao capsules alone， Xianling gubao capsules combined with routine treatment [OR＝2.85，95％CI（1.81， 4.48），P＜0.05] and routine treatment [OR＝2.93，95％CI（1.76， 4.86），P＜0.05] could significantly improve serum phosphorus level； network Meta-analysis ranking showed that routine treatment＞Xianling gubao capsules combined with routine treatment＞Xianling gubao capsules alone. CONCLUSIONS： Xianling gubao capsules combined with routine treatment can significantly improve therapeutic efficacy of PP patients， increase BMD and serum calcium level after treatment， but routine treatment is the best in improving serum phosphorous level.

Objective: To evaluate the clinical efficacy of percutaneous kyphoplasty (PKP) in the treatment of stage Ⅲ Kümmell＇s disease with no neurological symptom. Methods: From January 2009 to June 2018, 45 patients underwent PKP for stage Ⅲ Kümmell＇s disease with no neurological symptom at Department of Orthopaedics, The First Hospital Affiliated to Soochow University. They were 12 males and 33 females, aged from 61 to 85 years (average, 70.9 years). Their visual analog scale (VAS) scores for back pain, Oswestry disability indexes (ODI), heights of fractured vertebrae and kyphosis cob angles were recorded and compared between preoperation, one day, 3 months and final follow-up after operation. Results: All the 45 patients were followed up for 12 to 48 months (average, 28.0 months). Their VAS scores (2.4±0.7, 2.2±0.7 and 2.3±0.6), ODI sores (34.7±6.8, 34.2±6.5 and 34.1±6.6) and cobb angles (15.7°±2.2°, 15.8°±2.2° and 15.9°±2.4°) at one day, 3 months and final follow-up after operation were significantly lower than those (8.2±1.1, 75.3±9.0 and 25.2°±3.9°) before operation (P<0.001). Their anterior height ratios of the fractured vertebra (54.0%±4.3%, 53.7%±4.2% and 53.6%±4.0%) and median height ratios of the fractured vertebra (56.8%±4.0%, 56.5%±3.9% and 56.6%±3.9%) at one day, 3 months and final follow-up after operation were significantly higher than those (25.8%±3.9% and 27.2%±3.1%) before operation (P<0.001). The rate of cement leakage was 13.3%(6/45). No patients had neurological symptoms after operation. Conclusion PKP is a minimally invasive, safe and effective treatment for stage Ⅲ Kümmell's disease with no neurological symptom, because it can relieve the symptoms of the patients, restore the height of the fractured vertebral body and reduce the local kyphosis cobb angle.

Objective To evaluate the clinical effects of minimally invasive percutaneous new C2transpedicular lag-screw fixation for management of Hangman's fractures.Methods From October 2015 to June 2017,25 patients who had Hang-man's fracture were operated with minimally invasive percutaneous new C2transpedicular lag-screw fixation assisted by infrared navigation,among them there were 18 male and 7 female,aged from 28 to 70 years[average(46.1±13.3)years].According to the Levine-Edwards classification:16 patients were TypeⅠ,6 patients were TypeⅡand 3 patients were TypeⅡA.The cause of the in-jury was road traffic accident in 20 patients and fall from height in 5 patients.19 patients were simple Hangman's fracture and oth-er associated lesions included odontoid fracture of TypeⅡ(2 patients),atlas fracture of TypeⅠ(2 patients),rupture of spleen(1 pa-tient),and rib fractures(1 patient).According to American Association for spinal cord injury,graded as spinal cord injury D in 3 cases and E in 22 cases.The clinical outcomes were evaluated by visual analog scale(VAS)scores and related indicators,such as operation time,the range of motion(ROM)of cervical spine and ratio of bony union were recorded.The pre-and post-operative VAS scores of neck pain were compared with repeated measures analysis of variance. Results The mean follow-up time was (12.5±6.0)months,ranging from 3 to 24 months.Satisfactory reduction was obtained in all cases(minimal translation≤2 mm with-out obvious C2,3angulation).The average operation time was(65.9±12.1)min.At first day,one month,three months and the last fol-low-up, VAS scores of neck pain decreased comparing with preoperational measurements. There was significant difference be-tween the pre-and post-operative VAS scores of neck pain(t=24.7,25.8,23.1,24.1,P<0.001).According to American Associa-tion for spinal cord injury,three cases restored from D to E.There was no spinal cord or vertebral artery injury during operation and there was no screw loosing or breakage and cervical malformation happened during follow-up period. Bony fusion was achieved in all of these cases and the range of neck rotation was stored normal at the last follow-up.The average time of Bony fu-sion was(3.4±0.8)months.Conclusion The primary clinical efficacies of minimally invasive percutaneous new C2transpedicu-lar lag-screw fixation for treatment of Hangman's fracture were satisfactory,which carries precision and safety,immediate stability and more reliable.So it could be considered as a new choice for management of Hangman's fractures.

KylinRay-IMRT is the advanced radiotherapy treatment planning module of accurate radiotherapy system (KylinRay) aiming to provide accurate and efficient plan design platform. In this paper the system design, main functions and key technologies of KylinRay-IMRT were introduced. KylinRay-IMRT supports three dimensional conformal radiotherapy (3D-CRT), intensity modulated radiotherapy (IMRT) and many other types of treatment plan design with function modules including patient data management, image registration and fusion, image contouring, image three dimensional reconstruction and visualization, three dimensional conformal radiotherapy planning, intensity modulated radiotherapy planning, plan evaluation and comparison, and report print. KylinRay-IMRT has been tested by the national standard YY/T 0889-2013, the results showed that the performance of KylinRay-IMRT can fully meet the standard requirements.
Humans ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Conformal ; Radiotherapy, Intensity-Modulated ; Tomography, X-Ray Computed

Objective To investigate the risk factors affecting Sandwich vertebral re-fracture after vertebral augmentation surgery for osteoporotic spine Sandwich fractures.Methods A retrospective case control study was conducted on the clinical data of 90 patients with osteoporotic spine Sandwich fractures treated with vertebral augmentation surgery from January 2004 to December 2015.There were 26 males and 64 females,aged (69.9 ± 7.4) years.The patients were divided into fracture group (n =15) and non fracture group (n =75) according to the incidence of re-fracture after operation during follow-up.Gender,age,height,weight,bone mineral density,cumulative number of cemented vertebrae,location of the Sandwich vertebrae in the thoracolumbar segment,the preoperative kyphosis angle of the Sandwich fracture segment,surgical approach,cement injection approach (unilateral or bilateral),cement injection volume,cement leakage between the Sandwich intervertebral spaces,the postoperative kyphosis angle of the Sandwich fracture segment,and follow-up duration were used as independent variables.Chi-square test and multivariate logistic regression analysis were used to analyze the risk factors of vertebral Sandwich fracture.Results There were 97 Sandwich vertebrae in 90 patients,and 226 fractured vertebrae were treated with initial intensive treatment.The mean follow-up was 18.1 months.There were no significant differences in gender,age,height,weight,cumulative number of cemented vertebrae,whether the Sandwich vertebrae was located at the thoracolumbar segment,the preoperative kyphosis angle of the Sandwich fracture segment,the cement injection approach (unilateral or bilateral),the volume of cement injection,and the cement leakage between the Sandwich intervertebral spaces (P ＞ 0.05).There were significant differences in bone mineral density,surgical approach,and postoperative kyphosis angle of the Sandwich fracture segment between the two groups (P ＜ 0.05).Further logistic regression analysis showed that bone mineral density ≤ 3.5 SD and segmental kyphosis (≥ 10°) were risk factors for Sandwich fracture (P ＜ 0.05).Conclusions The low bone mineral density (T value ≤-3.5 SD) and postoperative kyphotic angle (≥ 10°) are risk factors for re-fracture of Sandwich vertebrae.Vertebroplasty itself does not increase the risk of recurrent vertebral fractures.