Objective To study the cellular senescence and molecular mechanism of olaparib in MCF-7 breast cancer cells.Methods The effects of olaparib on the proliferation and migration of MCF-7 cells were detected dynamically by real-time cell analysis(RTCA)technology.The effects of olaparib on the Senescence was detected by using the senescence-associated β-galactosidase(SA-β-gal).Quantitative polymerase chain reaction was used to analyze the effects of olaparib on the expression levels of genes encoding the senescence-associated factors p16,p21,C/EBP homologous protein,interleukin(IL)-6,IL-8,plasminogen activator inhibitor 1,phosphatase and tensin homolog deleted on chromosome 10,p27,retinoblastoma gene,Ki67,and E2F1.The effects of olaparib on the expression levels of the senescence-associated proteins p21,γH2AX,pRB,cyclin D1,insulin-like growth factor binding protein 3,and Ki67 were analyzed by Western Blot.Results Olaparib inhibited the proliferation and migration and induced the senescence of MCF-7 cells.Long-term(96 h)treatment with olaparib significantly up-regulated the gene expression levels of p16,p21,p27,C/EBP homologous protein,IL-6,IL-8,plasminogen activator inhibitor 1,phosphatase and tensin homolog deleted on chromosome 10,and retinoblastoma protein(P＜0.01)and significantly down-regulated the gene expression levels of Ki67 and E2F1(P＜0.01)in MCF-7 cells.Olaparib significantly increased protein expression levels of p21,γH2AX,and insulin-like growth factor binding protein 3 in MCF-7 cells(P＜0.01,P＜0.01,P＜0.05)and significantly decreased cyclin D1,pRB,and Ki67 levels(P＜0.05,P＜0.01,P＜0.05).Conclusions Olaparib can inhibit proliferation and migration and induce senescence in MCF-7 breast cancer cells.

Objective The equilibrium solubility and oil-water partition coefficient of caffeic acid in different pH environments were determined,and its biopharmaceutical classification system(BCS)classification was speculated.The dissolution curve of caffeic acid tablets was determined,and the above parameters were substituted into the rat PBPK model for modeling.Gastroplus software was used to predict the in vitro and in vivo correlation of caffeic acid tablets.Methods Quantitative analysis of caffeic acid was performed by a high-performance liquid chromatography in this research,the chromatographic column was Agilent Eclipse Plus C18(4.6 mm×250 mm,5 μm),the mobile phase was 0.32%glacial acetic acid solution-methanol(70∶30),the flow rate was 1.0 mL·min-1,the detection wavelength was 323 nm,the column temperature was 25℃,the injection volume was 10 μL.The equilibrium solubility,solubility volume(DSV)and oil-water partition coefficient(P)of caffeic acid in different pH buffers were measured by the shake flask method and n-octanol-water system,and its BCS classification was speculated.The dissolution curves of caffeic acid tablets in water,pH1.2,pH4.5 and pH6.8 were determined.The Z-Factor values of these dissolution curves were analyzed using Gastroplus software.The relevant parameters were substituted into the physiological pharmacokinetic(PBPK)model of rats to simulate the in vivo pharmacokinetic(PK)curve of rats.Compared with the measured PK curve that was reported previously,the correlation between in vivo and in vitro was speculated.Results The equilibrium solubility of caffeic acid in pH1.2,pH4.5 and pH6.8 were 0.676,1.266 and 4.624 mg·L-1,and the DSV were 443 787,236 967 and 64 879 mL,which showed that caffeic acid was an insoluble drug which had a strong pH dependence in dissolution;The oil-water partition coefficients(P)of caffeic acid in water,pH1.2 buffer,pH4.5 buffer and pH6.8 buffer were 4.33(logP=0.64),28.87(logP=1.46),19.77(logP=1.30)and 0.28(logP=-0.56),which indicated that caffeic acid was a BCS Ⅱ drug with high permeability.The results of the Cmax,tmax and AUC of caffeic acid in rats obtained by a software simulation was 0.358 μg·mL-1,0.39 h and 0.320 μg·h-1·mL-1,which was basically matched with the results[Cmax∶(0.250±0.037)μg·mL-1、tmax∶(0.33±0.12)h、AUC∶(0.303±0.024)μg·h-1·mL-1]that reported previously,so was the PK curves.Conclusion Caffeic acid is a drug with low solubility and high permeability.It is speculated that caffeic acid is a BCS Ⅱ drug,and its tablets show a high correlation in vivo and in vitro in rats.

Objective To establish the instability model of goat cervical vertebrae, and test biomechanical stability of the novel arc cervical titanium mesh with endplate ring. Methods The anatomical data from cervical vertebrae of adult goats were measured, so as to select a new type of arch cervical titanium mesh with endplate ring which was suitable for goat cervical vertebrae. A total of 24 goats with preserved articular capsule, ligaments and intervertebral disc were randomly divided into 4 groups. Group A (n=6, normal group) didn’t receive any special treatment, while Group B (n=6, model group) received partial resection of C4 vertebrae as well as upper and lower intervertebral disc. On the basis of models in Group B, Group C (n=6, experimental group) was installed with the novel arch cervical titanium mesh and fixed by plate and screw, and Group D (n=6,control group) was installed with traditional straight titanium mesh and fixed by plate and screw. The ranges of motion (ROMs) for 4 groups of specimens during flexion, extension, left/right lateral bending, left/right rotation under 2.0 N·m load were measured, and their three-dimensional (3D) motion stability was tested. The displacement of Group C and Group D under 200 N compression force was measured, the stiffness was calculated, and the anti settlement ability of the whole specimen was tested. Results The ROMs of Group A in all directions were smaller than those of Group B,the ROMs of Group A were larger than those of Group C, and the ROMs of Group C during flexion were smaller than those of Group D (P<0.05). The stiffness of Group C was higher than that of Group D (P<0.05).The compression displacement of Group C was smaller than that of Group D(P<0.05). Conclusions Compared with the straight titanium mesh, the novel arc titanium mesh is more consistent with the physiological curvature of cervical verebrae, and has better stability than the traditional titanium mesh during the most frequent flexion activities of cervical verebrae. Moreover, compression displacement of the novel arc titanium mesh under short-term stress is smaller than that of the straight titanium mesh, and its postoperative anti-settlement is better than that of the straight titanium mesh, which is worthy of further experiment and clinical promotion.

Objective To compare biomechanical properties of cortical bone trajectory (CBT) screw and traditional trajectory screw for fixing upper-middle thoracic spine. Methods The tomography images were obtained by CT scanning of normal T7 and T8 segments, and the three-dimensional (3D) model of T7-8 was reconstructed by Mimics software. The finite element model of upper-middle thoracic spine was established by optimizing FreeForm model and pre-processing function of ANSYS software. On this basis, the CBT screw and pedicle screw fixation models after discectomy were established, and 5 N·m flexion, extension, lateral bending and rotation loads were applied to the two model groups, respectively. The displacement and peak stress of vertebrae and implants under different working conditions were compared and analyzed. Results Under different loading conditions, the maximum displacement of CBT screw group was lower than that of pedicle screw group, and the range of motion of CBT screw group was lower than that of pedicle screw group. The stress level of both models was close, and the stress of CBT screw group was slightly lower than that of pedicle screw group. Under the load of flexion, extension and rotation, the maximum vertebral stress of pedicle screw group decreased by 31%, 17% and 18% compared with that of CBT screw group, and under lateral bending load, the vertebral stress of CBT screw group was 20% lower than that of pedicle screw group. Under the load of flexion and rotation, the maximum stress of pedicle screw group decreased by 2% and 11%; however, the maximum stress of CBT screw group was 11% and 1% lower than that of pedicle screw group. Conclusions The stability of CBT screw was better than that of pedicle screw, and the overall stress distribution was similar to that of pedicle screw. However, the vertebral stress distribution of CBT group was slightly inferior. The research findings provide a theoretical basis for the clinical application of cortical screw fixation after the failure in pedicle screw fixation for the upper-middle thoracic vertebrae.

Objective To observe the influence of the stress and displacement when the normal sacroiliac joint is exerted load simulating oblique-pulling manipulation, and to analyze the stress and displacement distribution when a three-dimensional finite element model of normal pelvis is exerted by oblique-pulling manipulation. Methods Lateral position was simulated on the three-dimensional finite element model of normal pelvis and it exerted loads horizontally forth and back, then the stress and displacement distribution were calculated. Results When the normal sacroiliac joint was exerted load simulating oblique-pulling manipulation, stress of the pelvis was mainly concentrated on the anterior inferior part of the left iliac fossa from the front view, with a maximum stress of 0.540E+07. The maximum value of internal and external strain of normal sacroiliac joint was 8.682 × 10-4m;the maximum value of anteropostreior strain was 3.337 × 10-4m;and the maximum value of up and down strain of normal sacroiliac joint was 3.284 × 10-4m. Conclusions The focus of the sacroiliac joint stress is mainly on the anterior and posterior superior borders when the normal pelvis exerted oblique-pulling manipulation. The internal and external strain of normal sacroiliac joint is maximal, the anteropostreior strain ranges the second, and the up and down strain is minimal.

Objective The aim of this study was to investigate the differences of the cell ultrastucture of normal mouse hatched blastocysts and their dormant ones cultured in vitro after freezing-thawing, and to explore whether the dor-mant embryos have a better anti-freezing shock property than the normal hatched mouse embryos .Methods By transmis-sion electron microscopy , the ultrastructure of these two types of mouse embryos was observed and analyzed .Results By comparative analysis of their ultrastructure , the results showed that the dormant embryos before freezing are being austerity and with lower energy metabolism at a ‘ground state ’ .After freezing-thawing and culture , their cellular structure seemed to be similar to that of the normal embryos cultured in vitro before freezing.However, after freezing-thawing and culture, the number of mitochondria decreased , the nuclei were loose , and their heterochromatin also increased .Conclusions From the ultrastructural observation , compared with the normal mouse hatched embryos , the cellular state of dormant mouse em-bryos after freezing-thawing is more favorable for material storage and energy metabolism , thus, indicating that they have a better anti-freezing property than normal hatched embryos .

Objective To investigate the stress characteristics of atlanto-axial bony structure under conditions of anteflexion,posterior extension,lateral flexion,and rotation after artificial atlanto-odontoid joint arthroplasty using three-dimensional finite element method and to improve the orientation of artificial atlantoodontoid joint from perspective of stress.Methods A three-dimensional finite element model of prosthetic atlanto-odontoid joint arthroplasty was created from CT images of the artificial atlantoodontoid joint and cervical vertebrae using software Mimics,Freeform,and Ansys.Stress characteristics of the model dealt with proneness,posterior extension,lateral flexion,or rotation loads were observed.Biomechanical performance of the bony structure of the model was analyzed and the orientation in improving the prosthesis was discussed.Results Anteflexion loading produced a maximum stress of 0.138 ×l08 N/m2 at the junction of lateral mass and posterior arch of the atlas,and 0.201 × 108 N/m2 at axial nail hole,contact point of plates with the axis,and posterior arch of the axis.Posterior extension loading produced a maximum stress of 0.666 × 107 N/m2 at junction of lateral mass and posterior arch of the atlas and 0.254 × 108 N/m2 at arch of the axis.Besides,stress concentration occurred at atlantoaxis nail hole.Right bending produced a maximum stress of 0.124 × 108 N/m2 at nail hole of right mass of atlas and 0.178 × 108 N/m2 at right contact point of the axis with plates.Right rotation produced a maximum stress of 0.847 × 107 N/m2 at junction of lateral mass and posterior arch of the atlas and 0.170 × 109 N/m2 at contact point of the axis with plates.The finite element model comprised 28 620 nodes and 107 441 units and provided good defining of the structural properties of artificial atlanto-odontoid joint arthroplasty.Under different loading conditions,the stress was mainly distributed in contact point of the vertebral body with plates,nail holes,junction of lateral mass and posterior arch of the atlas,and axial pedicle.Conclusions Prosthetic atlanto-odontoid joint scatters a part of the stress and alters the stress distribution of the atlas and axis from the intact condition.Finite element method can obtain complete analysis of the stress distribution of the artificial atlanto-odontoid joint arthroplasty.

BACKGROUND: Most reported biomechanical studies on sacroiliac joint injury and fixation use cadavers or artificial bone models to simulate the sacroiliac joint injury.OBJECTIVE: To analyze the vertical stability of anterior plate fixation for sacroiliac joint dislocation using three-dimensional finite element method. METHODS: The anterior plate fixation model of unilateral sacroiliac joint dislocation was constructed on the basis of the three-dimensional finite element model of a complete pelvis. An axial load of 500 N was applied on the model; the cloud pictures of stress, strain and displacement were obtained after calculation and compared with that of the complete pelvis under the same conditions.RESULTS AND CONCLUSION: Stress concentration occurred at the internal fixation system; the maximum stress was found at the screws near the injured sacroiliac joint, far greater than the maximum stress of the complete pelvis under the same condition. The maximum strain was found in the healthy sacroiliac joint; the fixed sacroiliac joint had no strain. The maximum displacement was found in the injured sacroiliac joint; it was about twice longer than the complete pelvis. These findings indicate that the vertical stability of pelvis is poor using anterior plate internal fixation treatment for sacroiliac joint dislocation; and stress concentration occurs at the screws and plates.

Objective To reconstruct anatomical structures and establish visible model of the hand and evaluate some key techniques of digitized virtual hand. Methods Three hands were scan and then perfused by self-curing denture acylic and cinnabar. With the datum from CT-scan of the specimen of perfused hand (cryopreserved 4-24 h), such anatomical structures as contour, bone, artery, extensor tendon, flexor tendon and nerve of hand were constructed by software of Mimics 10.01 and measured. Results The visible hand model based on anatomical structures was established and main anatomical structures were exactly showed. Each structure was displayed by the multiform solitude or combination. Vessel lumens was displayed hollow and fidelity. The hand nerve can the part demonstrate that can earnest reflect the normal human body nerve contour anatomy characteristic. Conclusion The visible hand model can provide 3D morphological data for clinical practice and research, as well as provide digitized model for virtual reality.

BACKGROUND: At present, there are very big differences in structure,material character and biological property between artificial intervertebral disc (AID) and normal physiological intervertebral disc.OBJECTIVE: Three-dimensional finite element method was used to observe and analysis the stress conduction of artificial lumbar intervertebral disc in lumbar motion segment.DESIGN: Single sample observation was designed.SETTING: Department of Orthopaedics, Third Affiliated Hospital, Sun Yat-sen University; Department of Orthopaedics, Second Affiliated Hospital, Sun Yat-sen University; Laboratory of Mechanics, Southern Medical UniversityPARTICIPANTS: It was to employ a vertebral sample without any spinal disorder of a healthy male died due to accidence and a finite element model of AID implantation in vertebral motion segment established with SB Charite Ⅲ AID.METHODS: According to industrial design chart of AID, finite element software MSC.MARK was utilized to establish three-dimensional model of artificial lumbar intervertebral disc. The corpus sample of motion segment of healthy lumbar vertebrae was collected and scanned with spiral CT machine and imaging documents were input in computer to preserve.Geometric model of L4-5 segment was established in three-dimensional coordinate system in ASC.MARK software. The intervertebral disc in L4-5 motion segment model was replaced by AID. It was to ensure the fixation of lower terminal lamina of L5 in the model. 4 Nm moment of force was exerted in anterior flexion, posterior extension, lateral bending and torsion on the sample successively. Finally, force of internodes representing AID was calculated and stress distribution was recorded.MAIN OUTCOME MEASURES: To observe stress distribution of anterior flexion, posterior extension, compression, lateral bending and rotation of AID.RESULTS: Finite element model of artificial lumbar intervertebral disc implanted lumbar motion segment that is in conformity with clinical practice was established. Stress distribution of AID was characterized as:er lamina was the maximum and that in the lower inclined part of slide of slide core and cover lamina was two or three times as same as that of sion, the stress in the center of slide core and cover lamina was the maximum.CONCLUSION: The finite element model of artificial lumbar intervertebral disc implanted lumbar motion segment established is in conformity with the structural character of practical artificial intervertebral disc in morphology, size and motion property, based on which, it is feasible to carry on the experiment on stress distribution of artificial intervertebral disc.