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Background and Objectives@#Glioblastoma (GBM) is an aggressive primary brain tumor characterized by its hetero-geneity and high recurrence and lethality rates. Glioblastoma stem cells (GSCs) play a crucial role in therapy resistance and tumor recurrence. Therefore, targeting GSCs is a key objective in developing effective treatments for GBM. The role of Parathyroid hormone-related peptide (PTHrP) in GBM and its impact on GSCs remains unclear. This study aimed to investigate the effect of PTHrP on GSCs and its potential as a therapeutic target for GBM. @*Methods@#and Results: Using the Cancer Genome Atlas (TCGA) database, we found higher expression of PTHrP in GBM, which correlated inversely with survival. GSCs were established from three human GBM samples obtained after surgical resection. Exposure to recombinant human PTHrP protein (rPTHrP) at different concentrations significantly enhanced GSCs viability. Knockdown of PTHrP using target-specific siRNA (siPTHrP) inhibited tumorsphere formation and reduced the number of BrdU-positive cells. In an orthotopic xenograft mouse model, suppression of PTHrP expression led to significant inhibition of tumor growth. The addition of rPTHrP in the growth medium counteracted the antiproliferative effect of siPTHrP. Further investigation revealed that PTHrP increased cAMP concentration and activated the PKA signaling pathway. Treatment with forskolin, an adenylyl cyclase activator, nullified the antiproliferative effect of siPTHrP. @*Conclusions@#Our findings demonstrate that PTHrP promotes the proliferation of patient-derived GSCs by activating the cAMP/PKA signaling pathway. These results uncover a novel role for PTHrP and suggest its potential as a therapeutic target for GBM treatment.
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Objective:To investigate the effect of total saponins of Panax notoginseng (TSPN) on learning and memory of post-stroke depression (PSD) rats and its mechanism.Methods:Four-vessel occlusion method was used to build the rat stroke model and 7 days later these rats were given solitary breeding with chronic unpredictable mild stress (CUMS) to make depression model. Rats were randomly divided into Sham group ( n=10), Model group ( n=10), PSD group ( n=10) and TSPN group ( n=10). The rats in the Model group and PSD group were injected administered with equal volume of 0.9% saline 30 min post-brain ischemia, one injection per day for 30 days. while TSPN group were treated with TSPN. The dose of TSPN (75 mg/kg) was dissolved in 0.9% saline 10 g/L, once per day for 30 days. Then the learning and memory of rats were tested by Morris water maze.The protein levels of DCX and Nestin in the hippocampus were detected by Western blot. Furthermore, the DCX/Ki67 co-labeled cells in the SGZ of hippocampus were observed by the immunofluorescence. Results:The escape latency at the fifth day of PSD group((31.8±3.8)s) was longer than that in the Sham group((10.4±3.2)s) and Model group((19.8±3.7)s) ( t=9.23, 5.15; both P<0.05). The escape latency ((14.2±2.8)s) of TSPN group was shortened significantly than PSD group ( t=8.56, P<0.05). The times across the platform in the Sham group was (10.3±1.7), and the PSD group was (4.1±1.1), difference was statistically significant between two groups( t=11.24, P<0.05). The times across the platform (8.4±1.6) of TSPN group statistically increased compared with PSD group ( t=5.77, P<0.05). The protein levels of DCX and Nestin in the PSD group were (0.60±0.02), (0.58±0.03) respectively, and in the TSPN group were (1.07±0.07), (0.95±0.11) correspondingly, there were significant differences of the DCX, Nestin protein level between the two groups( t=20.22, 7.68, both P<0.01). Moreover, there was significant difference in the number of the DCX/Ki67cells in the hippocampus SGZ between the PSD group((16.2±2.8) /mm 2) and TSPN group ((21.2±3.1) /mm 2)( t=2.42, P<0.05). Conclusion:TSPN could improve the learning and memory of the rats with post-stroke depression through enhancing the hippocampus neurogenesis.
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BACKGROUND:With the wide application and in-depth research of artificial hip joint, more secondary fractures around femoral prosthesis are reported. OBJECTIVE:To investigate the reasons, preventive measures, classification and treatment method of fractures around femoral prosthesis after artificial hip replacement. METHODS:The clinical data of the type classification, treatment method and clinical efficacy of fractures around femoral prosthesis after artificial hip replacement were retrospectively analyzed. The multi-level study was performed to investigate the trend of the relevant literatures. According to the Vancouver classification criteria, the various types of fractures and the results and complications of various treatment methods were analyzed, the treatment methods of different fractures were identified, and the effective and objective evaluation criteria were established to provide references for the clinical treatment. RESUTLS AND CONCLUSION:The fractures around femoral prosthesis after artificial hip replacement were closely related with the age of the patients, basic diseases, osteoporosis and selection of prosthesis type. The Vancouver classification criteria and treatment programs have guiding significance to the clinical efficacy. The fractures should be treated with different methods according to the different types in order to promote the fracture healing. The fractures around femoral prosthesis after artificial hip replacement were commonly treated with shape memory alloy embracing fixator, minimal y invasive fixation system, locking compression plate, al ograft cortical bone plates, carbon fiber, impaction bone grafting and renovation. In the practice application, various methods are often used in combination. For the patients with B2 and B3 type fractures, we should pay attention to the bone grafting around the fractures and the inner and outer medul ary cavity.
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BACKGROUND:Al ogenic bone is a clinical commonly used bone graft material, but the osteoinductive capacity is the biggest problem. OBJECTIVE:To evaluate the effect of al ogeneic bone combined with autologous bone marrow stem cells on the repair of bone defects after scraping or resection of benign bone tumors and tumor-like lesions. METHODS:Sixty-five cases of benign bone tumors (including patients with tumor-like lesions) were divided into two groups according to bone graft. There were 35 cases in the composite bone marrow stem cells for bone graft group, and 20-40 mL red bone marrow were extracted from anterosuperior iliac spine or iliac spine on both sides according to the expected amount of bone graft, then the bone marrow stem cells were isolated, purified, cultured and amplified for standby, and the bone marrow stromal stem cells and al ogeneic bone particles were ful y blended before bong graft. After tumor scraping or resection, the blended bone marrow stromal stem cells and al ogeneic bone particles were implanted into the bone defect region. In the bone graft group, the bone defect was implanted with al ogeneic bone soaked with saline for half an hour. X-ray examination was performed at 1, 3, 6 and 12 months after treatment to compare the fuzzy boundary and the time for disappear, and the postoperative complications were observed. RESULTS AND CONCLUSION:Al the 62 patients were fol owed-up for more than 12 months. The fuzzy boundary time and disappear time in the composite bone marrow stem cells for bone graft group were shorter than those in the bone graft group (P<0.05). In the composite bone marrow stem cells for bone graft group, one case appeared rejection and healed after treated with immunosuppressive agents for 2 weeks, and no complication observed in two groups. The results indicate that al ogeneic bone composite autologous bone marrow stem cells for bone graft can promote bone fusion and bone defect healing.
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BACKGROUND: The bone marrow stem cell (MSC) transplant treatment have the obvious superiority to tradition graft treatment for bone nonunion, but how to obtain the concentrated and highly effective bone marrow mesenchymal stem cell, as well as the dose-effect relations to fracture healing need further discussions. OBJECTIVE: To observe the curative effect of bone nonunion by using autologous MSC transplant treatment, and to compare with autologous iliac bone graft.DESIGN, TIME AND SETTING: Randomized controlled analysis was performed from January 1999 to June 2005 in the Affiliated Second Hospital of Hebei Northern College.PARTICIPANTS: The admitting 140 patients with humerus and tibia fracture were divided into 2 groups at random, autologous iliac bone graft group and autologous MSC transplant group, with 70 patients in each group. METHODS: Under aseptic condition, autologous MSC transplant group received puncture through posterior superior iliac spine, extracting bone marrow 10-20 mL from different spots, separating MSC using the density gradient centrifugation method, and counting as 4×10~9 nucleated cells/mL under the microscope for later use. In the autologous iliac bone graft group, bone fracture end was implanted with the suitable amount of iliac bone, while autologous MSC transplant group with the mixture of decalcified bone matrix and MSC, followed by suture. After the transplantation, external fixation may assist for 4-6 weeks according to the fixed degree of internal fixation.MAIN OUTCOME MEASURES: ① Bone callus formation and pain conditions in 2 groups at different time points after transplantation. ② Comparison of bone healing time between 2 groups. ③ Adverse events and side effects.RESULTS: According to intention-treatment analysis, experimental adopted 140 patients of humerus and tibia fractures, who all entered the final analysis. ① Bone callus formation and pain at different time points post-surgery: At 1 month after transplantation, bone callus formation in the fracture end was not obvious in autogenous iliac bone graft group, and could be seen in autologous MSC transplant group, both groups of fractures exhibited tenderness. At 2 months after transplantation, bone callus formation was observed in autogenous iliac bone graft group, fracture tenderness was relieved compared with the previous condition; in autologous MSC transplant group, a large number of bone callus formed, fracture tenderness was not obvious. At 3 months after transplantation, there were a large number of bone callus formations in autogenous iliac bone graft group, with slight fracture tenderness; in the autologous MSC transplant group, continuous bone callus formation appeared, without fracture tenderness. ② Bone healing time: The average healing time of autologous MSC transplant group was significantly shorter than autogenous iliac bone graft group [(5.5±1.5), (8.0±2.0) months, P < 0.05]. ③ Adverse events and side effects: Except 4 patients had iliac bone pain, all patients during the treatment had no infection and other complications, there were no re-fracture occurred at the follow-up of 8 months.CONCLUSION: The autologous MSC transplant treatment of exhibits a short duration and good effect for bone non-union, has obvious advantages over traditional bone graft.