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We explored the optimal regime in preventing or treating bone loss, using ovariectomised rodents loaded by mechanical stimuli with rest days during the loading cycle. Eighty-four Sprague-Dawley rats, aged 6 months, were randomly divided into 7 groups after bilateral ovariectomy. Mechanical vibration with 1-day rest (ML1R), with 3-day rest (ML3R), with 5-day rest (ML5R), with 7-day rest (ML7R), daily loading (DL), comparing the ovariectomised group (OVX) with baseline (BCL) measurements. After a recovery of one week, all the rodents were loaded daily by whole body vibration at 35 Hz and 0.25 g for 15 minutes. Eight weeks later, a three-point bending test of the radius and micro-CT scanning of the femoral head were performed after animal sacrifice. Large improvements in biomechanical properties occurred in all the experimental groups for failure load, elastic modulus and deflection, while a significantly enhanced efficacy was detected in ML7R compared with daily loading (p<0.05). In micro-CT scanning, bone volume fraction, trabecular thickness, number and separation were improved by the regime in all experimental groups, while ML7R showed a significant improvement over daily loading (p<0.05). Early bone loss in human subjects may be improved by high-frequency and low-magnitude whole body vibration with rest days or daily stimuli. Mechanical stimulus with a 7-day rest was more effective in improving biomechanical properties and micro-morphology compared with daily loading. This may have clinical implications in relation to the prevention and treatment of hip fractures, and in postoperative management following hip arthroplasty.
Osteosarcoma (OS) is the most common malignant primary bone tumor in the world. The cytotoxic T-lymphocyte antigen-4 gene (CTLA-4) is an important candidate gene for influencing the development of OS. This study aimed to investigate the potential association of CTLA-4 genetic polymorphisms with OS risk in Chinese Han population. A total of 415 OS patients and 431 healthy controls were enrolled in this study. The created restriction site-polymerase chain reaction (CRS-PCR) and DNA sequencing methods were used to detect the genotyping of CTLA-4 c.75G[C and c.326G[A genetic polymorphisms. We observed that the genotypes/alleles of c.75G[C and c.326G[A genetic polymorphisms were statistically associated with the increased risk of OS (for c.75G[C, CC versus (vs.) GG: OR 1.72, 95% CI 1.09–2.74; C vs. G: OR 1.30, 95% CI 1.06–1.60; for c.326G[A, AA vs. GG: OR 2.12, 95% CI 1.31–3.42; A vs. G: OR 1.31, 95% CI 1.07–1.61). The allele-C/genotype-CC of c.75G[C and allele-A/genotype-AA of c.326G[A may contribute to OS susceptibility. These data indicate that CTLA-4 genetic polymorphisms are potentially related to OS risk in Chinese Han population, and might be used as molecular markers for evaluating the risk of OS.
OSTEOSARCOMA (OS) is the most common pediatric bone malignancy that occurs primarily in adolescents and young adults in the world [1][2][3][4][5]. The exact mechanism of development of OS carcinogenesis still remains poorly understood. Patients with localized OS at presentation have a 60-80% rate of long-term survival, while metastatic disease carries a poorer prognosis [6,7]. It is estimated that the annual incidence rate for individuals less than 20 years old is 8.7 per million children, and account for ~ 6% of childhood cancer [8,9]. Several studies suggest that multiple factors such as genetic mutations and environment factors could affect the OS pathogenesis. However, the genetic factors could play key roles in the pathogenesis of OS [9][10][11][12][13][14][15] Republic of ChinaAbstract. Osteosarcoma (OS) is the most common pediatric bone malignancy worldwide. The MDM2 gene is an important candidate gene for influencing the susceptibility to OS. The objective of this study aimed to detect the potential association between MDM2 genetic variants and OS susceptibility in Chinese Han population. We recruited 415 OS patients and 431 cancer-free controls in this case-control study. The c.44C>T and c.1002T>C genetic variants in MDM2 gene were investigated using created restriction site-polymerase chain reaction (CRS-PCR) and PCR-restriction fragment length polymorphism (PCR-RFLP), respectively. We found that the genotypes/alleles of c.44C>T and c.1002T>C were statistically associated with the increased risk of OS (for c.44C>T, TT versus (vs.) CC: OR = 2.43, 95% CI 1.49-3.95, p < 0.001; T vs. C: OR = 1.36, 95% CI 1.11-1.67, p = 0.003; for c.1002T>C, CC vs. TT: OR = 2.38, 95% CI 1.37-4.13, p = 0.002; C vs. T: OR = 1.27, 95% CI 1.02-1.56, p = 0.030). The T allele and TT genotype of c.44C>T and C allele and CC genotype of c.1002T>C could be increased risk factors for the susceptibility to OS. Results from this study suggest that MDM2 genetic variants are potentially related to OS susceptibility in Chinese Han population, and might be used as molecular markers for assessing OS susceptibility.
The aim of this study was to investigate the influences of low-magnitude high-frequency vibration (LMHFV) with different rest period regimes (vibrational loading per day [with or without the loading divided into bouts]; or vibrational loading for 7 day followed by 7 day rest [with or without the loading divided into bouts]) on bone healing at multi-levels. Transverse fractures of rat bilateral tibias were established using a Kirschner wire inserted for fixation. The animals were randomly assigned to five groups (n = 7 for each group): four for vibrational groups by LMHFV with different rest period regimes and one for fractured model without mechanical loading. The macromechanical properties of the fractured tibias and the nanomechanical properties of the calluses were investigated through three-point bending and nanoindentation tests, respectively. Atomic force microscopy (AFM) was performed to analyze the nanostructure of the calluses. Micro-computed tomography (micro-CT) scanning was conducted to evaluate the microarchitecture of the calluses. The serum concentration of osteocalcin (OG) and tartrate-resistant acid phosphatase 5b (TRAP5b) were measured to assess the bone formation and resorption rates, respectively. Significantly higher values of failure load and elastic modulus were observed in DL (vibrational loading for 15 min per day) and DLR (vibrational loading per day in which three bouts of 5 min of vibration were separated by 4 h) than FBC (fractured model without mechanical loading) at macro-level (P < 0.05). The results of nanoindentation test showed the highest values of indentation modulus and hardness in DLR (significantly higher than FBC; P < 0.05); besides, higher value of hardness was also observed in DL (significantly higher than FBC; P < 0.05). Though AFM imaging showed no significant differences in grain sizes between the vibrational groups and FBC, roughness of DLR showed the highest value, i.e. it was significantly higher than that in FBC (P < 0.05). For microarchitectural parameters obtained from micro-CT imaging, tissue mineral density (TMD) of DLR and VL7 (vibrational loading for 7 day followed by a 7-day rest, 15 min per day during vibrational periods) were significantly higher than that in FBC (P < 0.05), but no significant differences in other parameters were observed between vibrational groups and FBC. There were no significant differences of OG between vibrational groups and FBC; however, FBC showed significantly higher TRAP5b concentration than all vibrational groups (P < 0.05). The results show that LMHFV with different rest period regimes not only altered the macro- and nano-level bone mechanical properties but also influenced the TMD of calluses and nano-level spatial arrangement (roughness) significantly. The most significant effect of LMHFV with different rest period regimes was observed in DLR, which indicated that both osteogenic accumulation and cellular resensitization can be satisfied under this regimen. Hence, the DLR group demonstrated a great potential in clinical appl...
Rationale: An extremely rare spontaneous pseudoaneurysm (PSA) of the posterior tibial artery (PTA) in a middle-aged male patient was cured by open surgery effectively. Patient concerns: A 53-year-old man presented with the increasing swollen left shank for 1 day, with intermittent pain, pulselessness and pallor. He denied the history of trauma, infection, and other diseases. Diagnoses: Physical examination, past medical history, ankle brachial index, ultrasonography, computed tomographic angiography (CTA), 3-dimensional reconstruction image of the popliteal artery and its branches and histological examination of intraluminal thrombus and clots helped us diagnose the patient as spontaneous PSA of PTA. Interventions: Our patient underwent excision of PSA and repair operation of PSA. Outcomes: The patient recovered well at 2-year follow-up. Lessons: This rare case provides valuable insights for tissue repair and vascular surgery. Therapeutic methods should be in accordance with the best interest of patient. Open surgery is the effective treatment for spontaneous PSA of PTA.
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