Objective:To investigate whether the combination of the advantages of deep learining in image processing and radiotherapy will make the radiotherapy process more intelligent.Methods:The generative adversarial network (GAN) is a generation model using neural network. High-quality dose distribution images can be generated by inputting relevant features. Firstly, random unconditional GAN was utilized to verify the ideal data, then conditional GAN (cGAN) was employed to train DICOMRT data of tumor patients, and the target contour information was used to directly generate dose distribution images.Results:For the verification of ideal data, the generation of ideal distribution yielded good effect. By extracting target contour and real dose slice data and using cGAN training, the dose distribution maps of planning target volume (PTV) and organs at risk (OAR) of tumor patients could be obtained. The absolute error evaluation of the maximum and average values between the predicted value and the real dose was shown as[3.57%, 3.37%](PTV), [2.63%, 2.87%](brain), [1.50%, 2.70%](CTV), [3.87%, 1.79%](GTV), [3.60%, 3.23%](OAR1) and[4.40%, 3.13%](OAR2), respectively.Conclusions:GAN model can be used to generate ideal dose distribution data, and cGAN model with prior knowledge can be employed to establish the relationship between target information and dose distribution. Directly generating the corresponding dose distribution image by inputting the target contour information is an effective attempt for dose prediction.

BACKGROUND:Biocompatibility is a key parameter in drug delivery systems. In general, to obtain a proper microparticle carrier, the materials themselves should have excellent biocompatibility. Besides, spherical degree and surface smoothness both have significant influence on biocompatibility.OBJECTIVE: To obtain spherical and smooth poly (lactide-co-glycolide)microparticles, so as to improve the property of biocompatibility.DESIGN: Open experiment.SETTING: Research Laboratory of Biomaterials, Jinan University.MATERIALS: The experiment was conducted in the Research Laboratory of Biomaterials, Jinan University, between June 2004 and January 2005.The materials included poly(lactide-co-glycolide), lysozyme and poly (vinyl alcohol). The other reagents were analytical pure. The instruments included a homogenizer, a mechanical stirrer, an ultrasonic cleaning instrument, a scanning electron microscope and an atomic force microscope.METHODS: ① Preparation of microparticles: Lysozyme was selected as a model protein for encapsulation into poly(lactide-co-glycolide) using a dou-ble emulsion solvent extraction/evaporation method. Three separation methods, namely direct vacuum freeze-drying, filtration and centrifugation,were investigated and compared. ② Observation under the scanning electron microscope: We observed the effect of three separation methods on the shape of microparticles. All the samples were attached to copper mounts and coated with gold, and then were observed with an electron microscope.③ Observation under the atomic force microscope: The morphological structure of the surface was analyzed with atomic force microscope.RESULTS: ① Observation results of scanning electron microscope: Compared with direct vacuum freeze-drying and filtration, centrifugation method was more efficacious in obtaining spherical and smooth microparticles based on the scanning electron microscope pictures. But results also warned us to be more careful when we prepared scanning electron microscope samples using ultrasonic to separate the aggregates. ② Atomic force microscope results indicated that the surface was smooth with the average roughness of 48.55 nm.CONCLUSION: By investigating the influence of different downstream processes, we can obtain spherical and smooth products. Besides, a new one-step method is put forward in constructing some microparticle-combined polymer based scaffolds because the combined scaffolds and microparticles are formed synchronously.

Objective To investigate the effect of small interference RNA(siRNA) targeting RRM2 on the biological behavior of human osteosarcoma cell line Saos-2 and the molecular mechanisms.Methods RRM2 expression was knocked down in human osteosarcama cell line Saos-2 by RRM2 siRNA.The expression of RRM2 mRNA and protein was determined in human osteosarcoma cell line Saos-2 and human osteoblast-like cell line hFOB1.19 by real time-PCR and Western blot.The cell proliferation was detected by CCK-8.The migration was observed by using transwell system.The apoptotic rate was observed by ELISA.The expression of CyclinD1 and Bcl-2 proteins were detected by Western blot.Results The expression of RRM2 mRNA and protein was higher in Saos-2 than in hFOB1.19.siRRM2 could down-regulate the expression of RRM2 in Saos-2 cells in a time-and concentration-dependent manner.CCK-8 assay showed that si-RRM2 could inhibit the proliferation ability of Saos-2 cells in a time-and concentrationdependent manner,but had no effect on the proliferation of hFOB1.19 cells.Transwell assay indicated that si-RRM2 could inhibit the migration of Saos-2 cells.si-RRM2 combined with adriamycin could increase the apoptosis of Saos-2 cells.Western blot showed that the expression of Cyclin D1 and Bcl-2 were decreased by silencing RRM2.Condusion RRM2 overexpression maybe associate with the osteosarcoma cells proliferation and migration and suppression of its function is a potential therapeutic strategy in osteosarcoma.

Osteonecrosis is the most common disorder in femoral head and scaphoid. However, avascular necrosis (AVN) in metacarpal head is a rare disease. In the present study, a 14-year-old male patient complained of right-hand pain with a limited range of motion for one month. Physical examination showed that the active flexion was 70° and the extension was limited to 30° of the metacarpophalangeal (MCP) joints. The grip strength decreased to 60% of the contralateral hand. X-rays demonstrated flattening and sclerotic changes in the long finger and ring finger of metacarpal head. CT scanning indicated cystic, osteochondral defects and sclerotic changes in metacarpal head. Imaging examination further confirmed the diagnosis of AVN in the long metacarpal finger and ring finger. After conservative treatments including splint immobilization, non-steroidal anti-inflammatory drugs (NSAIDs) and physiotherapy, the local pain symptoms of the MCP joint gradually disappeared. The range of motion of MCP joint returned to normal with the grip strength score as 105% of the contralateral hand. MRI confirmed excellent remodeling and regeneration in the metacarpal head at two years later. The clinical characteristics, diagnosis and treatments of AVN of metacarpal head were reviewed. Although radiograph examination is commonly used, early-stage osteonecrosis of the metacarpal head should be confirmed by MRI. Given the rarity of this disorder, there is no consensus on the treatments. Metacarpal necrosis is the more common disorder in adolescent patients with a history of trauma. Considering the potential of bone remodeling, juveniles with metacarpal head necrosis could recover by conservative treatments.

Objective To establish a doxycycline-controlled immortalized pre-cartilaginons stem cells (IPCSCs) strains, clone parathroid hormone-related peptide[PTHrP(1-36)] gene and construct re- sponsive plasmid, pTRE-PTHrP (1-36). Methods Plasmid pTet-on was transfected into IPCSCs by using LipoinfectaminTM 2000 and then the stable clones were obtained by G418 screening. The doxycyc- line was added into the medium of monoclonal cells that were transiently transfected with plasmid pTRE- 2Hyg-Lue. The total RNA was extracted from PCSCs and the PTHrP(1-36) gene obtained by RT-PCR method. Then, the PTHrP (1-36) gene was subcloned to plasmids of Tet-responsive element with the se- lection marker of hygromycin pTRE-2Hyg to construct recombinant eukaryotic expression plasmid pTRE- PTHrP(1-36). After transferred into E. coli-DH5α, the clone was amplified, the recombinant plasm0ids were purified and identified by double-enzyme digestion. Results The doxycycline induced IPCSCs line was obtained, with 50 times higher than the non-induced cell line. Double enzyme digestion analysis and sequencing showed that the target gene was cloned into recombinant plasmid. Conclusions The induced IPCSCs line can be used to highly express alien genes. The responsive plasmid containing PTHrP (1-36) gene may be premising for rigorous control of PTHrp (1-36) gene expression.

might be related to the growth and metastasis of HCC.

Atomic force microscopy (AFM) has been applied in many biological investigations in recent years, and this review focuses on the application of AFM in DNA-protein interactions. AFM images of static DNA-protein complexes, in air and in liquid, can be used to obtain quantitative and qualitative information on the structure of different complexes. And dynamic AFM images of DNA-protein complexation in real time under liquid conditions will help to understand biological processes and mechanisms at single molecule level. In addition, the measurement of intermolecular forces between biomolecules also provides new opportunities for studying mechanical properties of biomolecules and the interactions in their native environment. AFM has revealed many mechanisms of gene regulation, and will play a more and more important role in life science research.
DNA ; chemistry ; ultrastructure ; Humans ; Microscopy, Atomic Force ; methods ; Protein Binding ; Protein Interaction Mapping ; Proteins ; chemistry ; ultrastructure

Brain arteriovenous malformation (bAVM) is a common cerebrovascular disease in clinical practice. Compared with adults, children with bAVM are more prone to rupture and bleeding, and have a higher mortality and disability. Therefore, it is very important to accurately evaluate the bleeding risk of children with bAVM and reasonably select intervention measures to improve the prognosis. The treatment methods of children with bAVM mainly include conservative treatment, microsurgical treatment, endovascular embolization, stereotactic radiosurgery, and multimodal combined treatment. At present, the treatment indications and specific treatment options for children with bAVM are controversial.

Objective:In Shanghai Advanced Proton Therapy Facility (SAPT) of Ruijin Hospital Proton Therapy Center, the calculation accuracy of the commercial proton treatment planning system RayStation (V10), especially the accuracy of the proton range calculation, was measured and verified, aiming to provide reference for the clinical application of the treatment planning system.Methods:A head phantom was used to verify the calculation accuracy of RayStation. The phantom CT was imported into treatment planning system (TPS). The phantom was followed closely by a water tank with a one-liter cubic target. A single field verification plan with the prescribed dose of 200 cGy (relative biological effectiveness) was designed and implemented. Then, the measured distribution results were compared with the calculation results.Results:When the verification plan of the phantom was designed with the default settings of RayStation, the measured longitudinal dose distribution was approximately 4 mm deeper than that of TPS, indicating that RayStation overestimated the water equivalent thickness (WET) of the tissue substitute materials in the phantom. To study the range error, the actual beam was used to measure the WET of the soft tissue substitute material. The default setting of RayStation was fine-tuned according to the measured results. It was found that the error between the measured SOBP and TPS calculations was reduced to only 2 mm.Conclusions:Using the default setting of RayStation to calculate the stopping power of the phantom may cause a large range error. A method that combines tissue segmentation with the measured WET of the tissue substitute material is proposed to improve the range calculation accuracy of the TPS. The results show that the proposed method can improve the dose and range accuracy of the commercial TPS including RayStation for tissue substitute materials.

Objective:To calculate the single-event dose-averaged specific energy of particles delivered in spherical domains based on the track structure model and using triple integration, and to investigate the influence of the domain shape on the key model parameters of microdosimetric kinetic model (MKM) and its corresponding physical significance.Methods:The domains are assumed to be cylinders and spheres, respectively. With α 0, domain radius, rd, and nucleus radius, Rn, as undetermined coefficients, the nuclear charge numbers, kinetic energies and their corresponding LETs of three kinds of charged particles ( 3He, 12C, 20Ne) as independent variables, D10 as dependent variable, the mean value of squared residuals, J2, between the D10 calculated values and D10 experimental values as the optimization objective, the final fitting values of the above undetermined coefficients of human salivary gland (HSG) cells and Chinese hamster lung (V79) cells obtained after iteration by the robust least square method are the optimal model parameter values of MKM. Results:For HSG cells, cylindrical domain: α 0=0.073/Gy, rd=0.29 μm, Rn=4.1 μm, J2=0.039 7 Gy 2; spherical domain: α 0=0.023/Gy, rd=0.29 μm, Rn=4.4 μm, J2=0.039 3 Gy 2; For V79 cells, cylindrical domain: α 0=0.114/Gy, rd=0.25 μm, Rn=3.8 μm, J2=0.097 4 Gy 2; spherical domain: α 0=0.095/Gy, rd=0.26 μm, Rn=4.1 μm, J2=0.096 9 Gy 2. Conclusions:For the same type of cells, cylindrical and spherical domains were selected respectively, and there are significant differences in MKM parameters obtained by fitting. The fitting values of the domain radius, rd of the two shapes of domains show no significant difference, while the fitting values of α0 of spherical domains are smaller than those of cylindrical domains, the fitting values of nucleus radius, Rn, of spherical domain are larger than those of cylindrical domains, closer to the nucleus radius observed by fluorescence microscopy. In the low LET (<20 keV/μm) region, D10 calculated according to the parameters of the two different shapes of domains are different, so the selection of the domain shape will cause differences in the relative biological effectiveness(RBE) calculation of proton in the region near Bragg peak.