[目的]探讨影响Ⅰ级软骨肉瘤预后的因素.[方法]回顾分析2010年1月-2018年1月郑州大学第一附属医院收治的62例Ⅰ级软骨肉瘤患者的临床资料,采用Kaplan-Meier生存分析比较三类发病部位的两种手术方式对无复发生存率的影响,Cox回归分析影响生存的因素.[结果]随访时间24 ～ 96个月,平均(48.07±21.22)个月,3例患者复发后失访.随访过程中,5例患者出现远处转移,共2例患者死于肺转移,5年生存率96.77％.MSTS评分局部切除组为(28.27±0.65)分,广泛切除组为(25.68±1.45)分,两组间差异有统计学意义(P＜0.05).但是,术后5年无复发生存率,局部切除组为59.67％,广泛切除组为90.32％,差异有统计学意义(P＜0.05).患者是否复发的单因素分析表明,是否复发两组间在性别、年龄、部位、肿瘤直径、Enneking分期、位置分类方面的差异无统计学意义(P＞0.05),但复发组手术广泛切除的比率显著低于未复发组(P＜0.05).Ka-plan-Meier生存分析表明,广泛切除或局部切除对四肢肿瘤无复发生存率的影响差异无统计学意义(P＞0.05).但是,相较于局部切除,广泛切除在中轴组和胸壁组可以获得显著提升的无复发生存率(P＜0.05).Cox回归分析表明,手术方式(HR=9.495,95％CI:1.947～46.311,P＜0.05)是影响生存的独立预后因素.[结论]对四肢Ⅰ级软骨肉瘤,局部切除不增加复发风险且功能更佳.对胸壁、骨盆和脊柱Ⅰ级软骨肉瘤,应广泛切除以减少复发风险.

Background: Osteosarcoma is a malignant bone tumor common in children and adolescents. Metastatic status remains the most important guideline for classifying patients and making clinical decisions. Despite many efforts, newly diagnosed patients receive the same therapy that patients have received over the last 4 decades. With the development of high-throughput sequencing technology and the rise of immunotherapy, it is necessary to deeply explore the immune molecular mechanism of osteosarcoma. Methods: We obtained RNA-seq data and clinical information of osteosarcoma patients from TCGA database and TARGET database. With the help of co-expression analysis we identified immune-related lncRNA and then by means of univariate Cox regression analysis prognostic-related lncRNA was screened out. And also by using least absolute shrinkage and selection operator regression method a model based on immune-related lncRNA was constructed. The differences in overall survival, immune infiltration, immune checkpoint gene expression, and tumor microenvironmental immunity type between the two groups were evaluated. Results: We constructed a signature consisting of 13 lncRNA. Our results show that signatures can reliably predict the overall survival of patients with osteosarcoma and can bring net clinical benefits. Further more, the signatures can be used for further risk stratification of the metastasis patients. Patients in the low-risk group had higher immune cell infiltration and immune checkpoint gene expression. The results from gene set variation analysis show that patients in low-risk group are closely related to immune-related pathways when compared with patients in high-risk group. Finally, patients in the low-risk group are more likely to be classified as TMIT I and hence more likely to benefit from immunotherapy. Conclusion: Our signature may be a reliable marker for predicting the overall survival of patients with osteosarcoma. Keywords: Osteosarcoma, TCGA, LncRNA, Tumor immunology, Prognosis.

Necroptosis is a novel manner of programmed cell death and important for tissue development, homeostasis, damage, and repair. Activation of receptor-interacting protein kinase 3 (RIPK3), a key member of receptor-interacting protein family in contributing significantly to necroptosis, in tissues is a hallmark of cells dying by necroptosis. However, there are few studies that examine the expression of RIPK3 in the glandular cells of stomachs under physiological condition. We have therefore conducted this study to immunohistochemically characterize the key element of necroptosis, RIPK3, in the mouse and human stomach. Results showed that RIPK3 positive cells could be observed in the surface mucosal cells, granular cells, and lamina propria cells in both mouse and human stomach tissues. Ratios of PCNA/RIPK3 positive cells in the glandular cells were ~ 2.1 in mouse and ~ 4.15 in human sections respectively. Morphological and double immunofluorescence analysis confirmed that these RIPK3 positive cells were mucous, parietal and lamina propria cells. Our results indicate that the expression of RIPK3 in different cell types might contribute to cell turnover of gastric mucosa in the mouse and human stomach under physiological condition.

Objective:To study the correlation between WW domain-containing oxidoreductase (WWOX) expression and clinicopathological features of osteosarcoma, and explore the effect of WWOX on the proliferation and metastasis of human osteosarcoma in mice.Methods:The expression of WWOX in osteosarcoma tissues was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry. The correlation between the WWOX expression and clinicopathological features of osteosarcoma was evaluated. The osteosarcoma cells 143B were injected into the tibias of immunodeficient mice to establish the osteosarcoma xengrafted model. Lentivirus, lentivirus-delivered WWOX and lentivirus-delivered WWOX short hairpin RNA (shRNA) were injected into tumor respectively. The tumor growth was recorded and compared. The number of pulmonary nodules was assessed using micro CT. For the measurement data that conform to the normal distribution, the independent sample t test was used for difference analysis; for the measurement data that do not conform to the normal distribution, the nonparametric test was used for difference analysis; for the grade data, the nonparametric test was used for difference analysis; for the count data, the test was used for difference analysis. The differences between different groups were analyzed by one-way ANOVA.Results:There was no significant correlation between WWOX expression and some clinicopathological features, including gender, age, primary site, etc. The high WWOX expression was correlated with low microvascular density (MVD) and small tumor volume. The overall survival (OS) and disease-free survival in patients with high WWOX expression was obviously longer than those of patients with low WWOX expression. The growth rate of primary tumor in immunodefient mice was significantly lower in WWOX group and significantly higher in WWOX shRNA group than in vector group. The number of pulmonary nodule was significantly greater in WWOX shRNA group than in vector group. However, there was no significant difference in the number of pulmonary nodule between WWOX group and vector group. WWOX was expressed in a higher level in primary tumor in WWOX group and lower level in WWOX shRNA group than in vector group. WWOX was expressed in the lower level in pulmonary nodule in WWOX shRNA group than in vector group. MVD was expressed in a lower level in primary tumor in WWOX group and higher level in WWOX shRNA group than in vector group. MVD was expressed in the higher level in pulmonary nodule in WWOX shRNA group than in vector group. However, there was no significant difference in WWOX level and MVD between WWOX group and vector group. We further found that WWOX could regulate the expression of proliferation cell nuclear antigen (Ki-67) and matrix metalloproteinase (MMP)-2 through extracellular signal-regulated kinase (ERK) phosphorylation, and further regulate the proliferation and invasion of osteosarcoma.Conclusion:The high expression of WWOX is associated with better prognosis in osteosarcoma. WWOX can inhibit the growth of tumor bearing osteosarcoma in mice with immunodeficiency through ERK signaling pathway, and inhibit the angiogenesis and lung metastasis of tumor bearing osteosarcoma in mice with immunodeficiency.

Objective:To explore the methods, complications and follow-up results of limb salvage for primary malignant tumors of the femoral shaft.Methods:From October 2006 to October 2019, 41 cases of primary malignant tumors of femoral shaft were analyzed retrospectively, 37 cases were followed up, including 22 males and 15 females, aged 8-46 years with an average age of 20.56±4.72 years old. All the lesions were located in the femoral shaft, and The Enneking stage was IIB. Tumor lesion ranged in the femur from 10 cm to 24 cm, and there was no pathological fracture. Pre-operative puncture biopsy was performed in all cases.22 cases were confirmed as osteosarcoma, 8 as chondrosarcoma, 5 as Ewing sarcoma, 2 as malignant fibrous histiocytoma. Neoadjuvant chemotherapy has been used to treat both osteosarcoma and Ewing sarcoma. Among the 37 patients, 8 cases of patients received total femoral prosthesis replacement, 14 cases of intramedullary nail fixation with allogenic bone graft, 8 cases of allograft-prosthetic composite (APC), and 7 cases of 3D printed prosthesis. The limb function was graded according to MSTS 93 system.Results:37 out of 41 patients were followed up, and the average follow-up time was 23.15±16.74 months (6-62 months). There were 9 patients with pulmonary metastases (26.47%), among which 6 patients passed away due to multiple metastases. 28 patients survived without tumor at last follow-up. The MSTS score was18-28 (average of 22.55±2.57). The average score of 3D printing prosthesis group was 27±1.74, allogeneic bone transplantation group was 22.85±2.59, total femoral prosthesis replacement group was 20.25±2.25, and the APC prosthesis group was 20.5±2.07. There was statistical difference between 3D printing group and other groups. The overall excellent and good rate of lower limb function was 79.41%, in which the 3D group was 100%, allogeneic bone group was 78.5%, APC prosthesis group was 87.5%, total femoral prosthesis replacement group was 62.5%. There was no statistical difference in the excellent and good rate of limb function among the groups. There weren't any cases of hip joint dislocation after total femoral prosthesis replacement. Delayed union of bone healing was seen in 3 cases of allogeneic bone transplantation and 2 cases APC patients. One patient suffered from the postoperative hemorrhage-related diseases-sciatic nerve compression, and the nerve recovered after emergency debridement. One patient suffered from poor wound healing. The overall complication rate was 24.32% (9/37).Conclusion:The patients with primary malignant tumors of the femoral shaft can effectively recover the lower extremity function by choosing the appropriate surgical scheme, in order to achieve the purpose of limb preservation and improve the quality of life of the patients. 3D printing prosthesis provides a new choice in the treatment of femoral shaft tumors.