Metastasis is the leading cause of death from cutaneous melanoma. Identifying metastasis-related targets and developing corresponding therapeutic strategies are major areas of focus. While functional genomics strategies provide powerful tools for target discovery, investigations at the protein level can directly decode the bioactive epitopes on functional proteins. Aptamers present a promising avenue as they can explore membrane proteomes and have the potential to interfere with cell function. Herein, we developed a target and epitope discovery platform, termed functional aptamer evolution-enabled target identification (FAETI), by integrating affinity aptamer acquisition with phenotype screening and target protein identification. Utilizing the aptamer XH3C, which was screened for its migration-inhibitory function, we identified the Chondroitin Sulfate Proteoglycan 4 (CSPG4), as a potential target involved in melanoma migration. Further evidence demonstrated that XH3C induces cytoskeletal rearrangement by blocking the interaction between the bioactive epitope of CSPG4 and integrin α4. Taken together, our study demonstrates the robustness of aptamer-based molecular tools for target and epitope discovery. Additionally, XH3C is an affinity and functional molecule that selectively binds to a unique epitope on CSPG4, enabling the development of innovative therapeutic strategies.

Objective To investigate the effect of H₂O₂-induced oxidative stress on autophagy and apoptosis of human bone marrow mesenchymal stem cells (hBMSCs). Methods hBMSCs were isolated and cultured. The cells were divided into control group, 3-MA group, H₂O₂ group, H₂O₂ combined with 3-MA group. DCFH-DA staining was used to analyze the level of reactive oxygen species (ROS). hBMSCs were treated with 0, 50, 100, 200, 400 μmol/L H₂O₂, and then the cell viability was detected by CCK-8 assay. The level of autophagy was detected by monodansylcadaverine (MDC) staining and LysoTracker Red staining. The cell apoptosis was detected by flow cytometry. Western blotting was used to detect the expression of beclin 1, mTOR, phosphorylated mTOR (p-mTOR), cleaved caspase-3(c-caspase-3) and caspase-3 proteins. Results Compared with the control group and 3-MA group, ROS level and autophagosomes were increased and the proliferation and apoptosis were decreased in H₂O₂ group. The protein expression of beclin 1, mTOR, c-caspase-3 was up-regulated, while the p-mTOR was down-regulated. Compared with the 3-MA group, the H₂O₂ combined with 3-MA group also had an increased ROS level and autophagosomes, but not with significantly increased apoptosis rate; The protein expression of beclin 1, mTOR, c-caspase-3 was up-regulated, and the p-mTOR was down-regulated. Conclusion H₂O₂ can induce hMSCs to trigger oxidative stress response. It enhances the autophagy and inhibits the proliferation and apoptosis of hBMSCs.
Humans ; Beclin-1/metabolism* ; Caspase 3/metabolism* ; Reactive Oxygen Species/metabolism* ; Hydrogen Peroxide/pharmacology* ; Apoptosis ; TOR Serine-Threonine Kinases/metabolism* ; Oxidative Stress ; Autophagy ; Mesenchymal Stem Cells/metabolism* ; Cell Proliferation

Objective The study reviewed the exchanges and the outcome of the research cooperation of the platform of the Beijing International Cooperation Base for Science and Technology (ICBST),to explore a combined mode of internationalized research management of "base","talents" and "projects".Methods To analyze the outcomes of talents programs,international research cooperation projects and publications with the support of the Beijing ICBST.Results The establishment of BICBST has nurtured research talents to develop international vision,facilitated project-oriented international research cooperation,and encouraged high level research publication and grants.Conclusions ICBST is of great significance for the implementation of international research cooperation,which brought in more resources,cultivated a group of creative research talents,and broadened the channels for international collaborations and achieved capacity and influence of international competitiveness.

Objective To understand and analyze the effect and impact on Hospital-level Young Scholar Scientific Research Program in personal training and project promoting.Methods To review and analyze the archived documents and data materials of total 402 Young Scholar Scientific Research Program involving 339 young fellows from 2003 to 2013,compared the research input and output with general hospital level,including getting new fund,publications,Awards and patent.Results Output on researchers with Young Scholar Scientific Research Program is much higher than the general hospital level,but showing unbalanced distribution in medical disciplines.Conclusions To establishment of Young Scholar Scientific Research Program has achieved very good effect in promoting research in tertiary public hospital as well as has empowered the young fellows for conducting scientific research independently.It is proposed to go on strength the scientific management and optimize the system construction of research input,further establishing academic communication platform for young fellows.

Objective To establish a stable lung cancer A549 cell line transfected by AMP-activated protein kinase (AMPK) expression vector,and to observe the effect of AMPK on proliferation as well as on the invasive ability of A549 cells.Methods Full-length of AMPK gene was amplified and its target gene was digested,then inserted into the GV358 plasmid.Co-tranfected 293T cells were subjected to the lentivirus equipment package.Subsequently,we collected the lentivirus supernatant to infect the A549 cells and establish a stably,overexpressed cell line A549.The mRNA and protein of AMPK were examined by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and Western blotting.The proliferation and invasion abilities of A549 cells were detected by methyl thiazolyl thiazolium (MTT) and Transwell assay.Results GV358-AMPK lentivirus vectors was successfully constructed by restrictive enzyme digestion and plasmid sequencing.There were significantly increased expressions of AMPK protein (5.87 times,P =0.002) and mRNA (16.12 times,P ＜ 0.001) after transfected with GV358-AMPK compared with the Vector group.Meanwhile,AMPK overexpression showed significantly lower proliferation (the forth day:0.53 ± 0.03 vs.0.64 ±0.05,P=0.021;the fifth day:0.58 ± 0.04 vs.0.80 ± 0.07,P =0.002) and weaken invasive ability [(1.6±0.5) ×l05 vs.(3.4±0.3) ×105,P=0.004] ofA549 cells.Conclusion The lentiviralAMPK expression vector and its A549 cell line is successfully constructed.AMPK overexpression inhibits the proliferation and invasive ability of A549 cells.

Objective To investigate the anatomical changes and dose distribution deviations of locally advanced nasopharyngeal carcinoma ( NPC ) patients during intensity-modulated radiation therapy ( IMRT) . Methods Weekly cone beam CT ( CBCT) was applied to investigate the anatomical changes of enrolled 18 patients with locally advanced NPC. Dosimetric deviations were investigated with new IMRT plans after 20 fractions. Results The volumes of gross tumor volume ( GTVnx ) and GTVnd were decreased by 3. 15% and 5. 67% weekly, and decreased by a total of 22. 03% and 39. 68%, respectiely. The volumes of left and right parotids were decreased by 4. 93% and 5. 26% weekly, and decreased by a total of 29. 60% and 31. 56%, respectively. The volumes of GTVnd and parotids showed significant retraction in the first four weeks of radiation, then the retraction slowed down. The D95 of PGTVnd in Plan 2 decreased by 2. 20% (t=2. 382, P <0. 05) compared that in the initial Plan 1, while there was no significant difference on the D95 of PGTVnx , PTV1 and PTV2 . The Dmean , D50 and V30 of the left and right parotids in Plan 2 increased by 7. 34%, 12. 68%, 10. 90% (t = -3. 376, -3. 738, -3. 679,P<0. 05), and 6. 13%, 11. 17%, 9. 72% (t= -2. 550, -2. 446, -2. 673, P<0. 05), respectively, compared with Plan 1. The Dmean of larynx increased by 8. 69% in Plan 2 compared with Plan 1 ( t = -3. 099, P <0. 05). The D95 of PGTVnd in Plan(1+2) increased by 1. 37% (t= -3. 555, P<0. 05) compared with Plan 2. The Dmean, D50 and V30 of the left and right parotids in Plan(1+2) were decreased by 2. 90%, 2. 73%, 4. 62% (t=3. 089, 2. 718,2. 705, P < 0. 05), and decreased by 3. 49%, 3. 44%, 3. 80%(t=2. 781, 2. 958,4. 275, P<0. 05), respectively, compared with Plan 1. The Dmean of larynx decreased by 3. 29% (t=2. 747, P<0. 05) in Plan(1+2) compared with Plan 1. Conclusions The volumes of GTV and parotids of locally advanced NPC patients showed significant shrinks during IMRT. Replanning is necessary during the middle of IMRT to improve the target coverage and to spare the organ at risks ( OARs) .

Objective:A study was conducted to determine the expression of acetyl-coa carboxylase product of phosphorylation (P-ACC) and an enzyme called cyclooxygenase 2 (COX-2) in non-small cell lung cancer (NSCLC) tissue, as well as the relationship and correlations between tumor size, lymph node metastasis, clinical stage, and pathological type. Methods: Sixty-two patients with NSCLC lung cancer tissues were included in the patient group, whereas 20 patients who underwent lobectomy for other reasons and had normal lung tissues were included in the control group. Immunohistochemical streptavidin peroxidase method was used to detect the expression of P-ACC and COX-2 in lung cancer and normal lung tissues. Results:The positive expressions of P-ACC and COX-2 in NSCLC lung cancer and normal lung tissues were significantly different (P<0.05). In NSCLC tissues, the positive expression of P-ACC was significantly associated with tumor size (P<0.05), but was not significantly associated with lymph node metastasis, clinical stage, and pathological type. We found no correlation between the positive expression of COX-2 and tumor size, lymph node metasta-sis, clinical stage and pathological type. Further analysis revealed that the positive expression of P-ACC and COX-2 in NSCLC was sig-nificantly and negatively correlated (r=-2.37, P=0.032). Conclusion:The positive expression of COX-2 in NSCLC greatly increased compared with that of P-ACC, and a significantly negative correlation was observed between them. We propose that the positive expres-sion of P-ACC reduction may activate the positive expression of COX-2 and promote the occurrence, development, invasion, and metas-tasis of NSCLC.

Arthroplasty, Replacement, Knee ; adverse effects ; Female ; Humans ; Knee Joint ; diagnostic imaging ; surgery ; Middle Aged ; Radiography

Objective To explore the relationship between CD146(MCAM),microvessel density(MVD)in renal cell carcinoma(RCC) and its clinic-pathology,and to explore their correlation with clinic-pathologic parameter of RCC. Methods Immunohistochemisty was employed to determine the expression of CD146 and MVD in 43 RCC tissues and 20 normal control renal tissues. Results The positive expression of CD146 in RCC(90.7 ％,39/43) was remarkably higher than that in normal renal tissue(30.0 ％,6/20)(x2=27.77,P＜0.05).The expression of CD146 was not correlated with the category of RCC (x2=1.37,all P ＞0.05),but had a significant correlation to(the tumor volume x2=7.57)clinical stage(r=0.62) and metastasis of RCC(x2=19.99,P＜0.05). The MVD of RCC [(78.00±23.10)/200HP]was significantly higher than that of normal renal tissue [(23.05±7.93)/200HP].The MVD of CD146 was not correlated with the tumor volume and category of RCC (t=1.33,t=1.46,au P＞ 0.05),but had a significant correlation to clinical stage and metastasis of RCC (t=2.37,t=2.10,P＜ 0.05). There was a positive correlation between expression of CD146 and MVD in RCC(r=0.74,P＜0.05). Conclusion The overexpression of CD146 in RCC has a significant relation with tumor angiogenesis.The expression of CD146 and angiogenesis might serve as an important indicator of the development, progress and metastasis of RCC.

Objective To investigate the stress distribution of the femur after cemented prosthetic replacement in aged patients with comminuted intertrochanteric fracture and to analyze the difference of stress distribution between cemented long and short stem prosthesises.Methods A volunteer's left femur image data was obtained by spiral CT tomography.Then,the three-dimensional model of the femur was reconstructed with Mimics and Unigraphics modeling softwares.Based on the above analysis,we established three-dimensional modles of comminuted intertrochanteric fracture,long stem and short stem prothesises,and mantle layer of cement.Finally,we established the three-dimensional finite element model of these materials with software ABAQUS6.5,and carried out finite element analysis to the model in biomechanics.Results The stress disrilbution of the femur after cemented long and short stem prosthetic replacement didn't change significantly.The stress distribution of short stem between cement and prothetic stem were in the correlative area of distal end of the prothesis,and the lateral peak value was 21.3 MPa which exceeds the fatigue strength of bone cement;However,that of long stem were in the middle of medial interface and in the distal end of bilateral interface.There was no significant stress concentration zone in the mantle layer of cement which was used to reconstruct calcar femorale.Conclusion The stress distribution of the femur didn't change significantly after treating comminuted intertrochanteric fracture of aged patients with cemented long and short stem prosthesises.The cemented long stem prosthesises may be more suitable to treat these patients for its lower loosening probability.