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Objective:To observe the expression characteristics of small ubiquitin-like modified protein (SUMO) pathway members in osteosarcomaby using molecular biology methods, and provide theoretical basis for targeted therapy based on protein SUMO modification.Methods:Eighteen fresh osteosarcoma tissue samples surgically resected at Tianjin Cancer Hospital from January 2017 to June 2019 were collected. Western blot and immunohistochemical methods were used to detect the protein expressions of SUMO1, SAE1, Ubc9, and SENP1, which are core members of SUMO pathway, in the cancerous and adjacent tissue. Taking osteosarcoma cell line 143B as the research object, three targeted treatment regimens were designed and grouped as follows: control group, nonsense group, siR-SUMO1 group, siR-Ubc9 group, and SENP1 group. Western blot was used to verify the efficiency of gene transfection, the positive expression rate of EdU was detected by cell proliferation detection kit, the ability of cell migration and invasion was measured by scratch test and Transwell invasion test, and the apoptosis rate was detected by flow cytometry. Bone marrow mesenchymal stem cells (BMSCs) were used to evaluate the side effects of three treatment regimens.Results:Results from Western blot and immunohistochemistry showed that the protein expression levels of SUMO1, SAE1, andUbc9 in osteosarcoma tissues were significantly higher than those in adjacent tissues ( P<0.05), but SENP1 was significantly lower than in adjacent tissues. The experimental results based on 143B osteosarcoma cells showed that the siR-SUMO1 group, siR-Ubc9 group, and SENP1 group can significantly inhibit the activation of SUMO pathway in osteosarcoma cells, showing lower tumor cell proliferation ( P<0.05), slower cell migration and invasion capacity ( P<0.05), and higher apoptotic rate ( P<0.05), than the control group and nonsense group; however, experimental results based on BMSCs showed that the siR-SUMO1 group and siR-Ubc9 group can significantly inhibit the proliferation of BMSCs, induce apoptosis, and show great therapeutic side effects, but the SENP1 group has almost no effect on the proliferation and apoptosis of BMSCs ( P>0.05). Conclusion:The SUMO pathway is abnormally activated in osteosarcoma. Exogenous supplementation or endogenous activation of SENP1 is one of the alternatives for targeted osteosarcoma treatment.
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Objective Based on lung cancer center database,we analyzed the clinical characteristics of lung patients with bone metastases.The relationship between bone metastases,skeletal-related events,survival time and different pathological subtypes of lung cancer were also evaluated in this study.Methods A total of 861 patients with lung cancer were studied from May 2010 to April 2012 at Tianjin Medical University Cancer Institute and Hospital.As to follow-up situation,patients' survival status and treatment information were collected by telephone follow-up and (or) examinationsin outpatient.The clinical characteristics,skeletal-related events and survival of bone metastaticpatients with different pathological types of lung cancer were analyzed.Logistic regression analysis was used to identify risk factors for bone metastases.The relationship between histological subtypes and the incidence of bone metastases was evaluated using Odds Ratios (ORs).The chi-square test was used to compare the proportion of bone metastases,synchronous bone metastases and SREs among different histological subtypes patients.The overall survivals was evaluated using the Kaplan Meier.Results A total of 861 patients with lung cancerwere enrolled in this study,including 293 cases with bone metastases.The average follow-up of our population was 14.2 months and the last follow-up time was September 2017.Among different pathological types of lung cancer,adenocarcinoma (39.14％,173/442) has the highest incidence of bone metastases,followed by other types (29.91％,35/117),squamous cell carcinoma (29.47％,56/190) and SCLC (25.89％,29/112).Spine (59.73％,175/293) was the most common location site of the bone metastases,followed by the ribs (49.15％,144/293),pelvis (20.48％,60/293),femur (16.38％,48/293) and sternal (16.38％,48/293).Lung adenocarcinoma was a risk factor for bonemetastases (P=0.002).In ORs analyze,adenocarcinoma patients were more likely to develop bone metastases [OR=1.60,95％CI (1.21～2.13)].In our cohort,58.36％of patients with lung cancer had skeletal related events.Among various types of skeletal related events of patients with bone metastases,the most common one was radiotherapy for bone metastases (51.88％,152/293),followed by pathological fractures (15.02％,44/293),spinal cord compression (6.48％,19/293),bone instability requiring surgery (4.78％,14/293) and hypercalcemia (1.71％,5/293).There was no significant difference between different types of skeletal related events.The median survival time of the patients with bone metastases was 11.5 months.There was no significant difference in survival between adenocarcinoma patients and non-adenocarcinoma patients (P=0.111).Conclusion This study suggested that the incidence of bone metastasis in lung adenocarcinoma was 39.14％ and lung adenocarcinoma was a risk factor for bone metastases,which supported early screening and monitoring of bone metastasis in the patients.
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Objective@#To summarize the clinical data including manifestations, diagnosis, treatment and prognosis of eosinophilic gastroenteritis (EGE) in children.@*Methods@#A retrospective analysis was performed in 71 patients with pathologically proven EGE at Beijing Children's Hospital Affiliated to Capital Medical University from January 2008 to January 2017. Their clinical manifestations, laboratory and imaging examinations, endoscopic findings, histopathological examinations, and treatment were collected and analyzed.@*Results@#Among 71 EGE cases, 47 (66%) cases were male and 24 (34%) cases were female, and the median age was 9.2 (0.2-16.5) years old. The main clinical manifestations included abdominal pain (76%, 54/71), vomiting (68%, 48/71), anorexia (54%, 38/71), weight loss (38%, 27/71), and diarrhea (37%, 26/71). There were 27 cases (38%) with a history of allergic diseases or family history. The median absolute value of eosinophil in peripheral blood of the 71 patients was 0.4 (0-36.8)×109/L, and 27 cases (38%) showed an increase in eosinophil counts. Serum IgE was measured in 52 patients (104.3 (3.4- 3 000.0)×103 U/L), and 30 patients (58%) showed an increase in serum IgE. A large number of eosinophils ((41.0±8.5)/HP) were found in 3 patients' ascites. The endoscopic examination of upper gastrointestinal tract revealed hyperemic edema in 62 cases (87%), plaque in 44 cases (62%), erosion in 17 cases (24%) and ulceration in 16 cases (23%). Histopathologically, in 8 cases (11%) the disease involved both stomach and duodeneum, in 21 cases (30%) involved stomach only, and in 37 cases (52%) involved duodeneum only. In addition, in 6 cases (8%) the disease involved esophagus and in 10 cases (14%) involved colorectum. Microscopically, eosinophil counts averaged 67/HP, 33/HP, 40/HP and 38/HP in esophageal, gastric, duodenal and colorectal mucosa respectively. A total of 34 cases were treated with glucocorticoid, and all these patients had alleviation of symptoms, which occurred within 14.9 days on average, but EGE recurred in 11 cases (32%).@*Conclusions@#The clinical symptoms and endoscopic findings of EGE are diverse and nonspecific. Histopathological examination of gastrointestinal mucosa is particularly important for the diagnosis. Glucocorticoid treatment is effective, but the patients with EGE are prone to relapse.
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Objective:Prostate cancer frequently metastasizes to the spine. In this study, we investigate the prognostic factors as-sociated with survival in patients with prostate cancer accompanied by spinal metastases at their preliminary diagnosis. Methods:Clin-ical data of 49 patients who were diagnosed with spinal metastasis from prostate cancer between January 2005 and December 2010 were analyzed. Variables including alkaline phosphatase (ALP), previous skeletal-related event, Gleason score, prostate-specific anti-gen (PSA) nadir, and time to castration resistance were obtained. Moreover, the relationship between these variables and overall sur-vival (OS) was analyzed. Survival analysis was performed by using Kaplan-Meier curves. Furthermore, the differences among the OS rates were assessed by using the log rank test. The variables were statistically significant in the univariate analysis (P<0.05) and were included in the multivariate model. Results:The average follow-up time was 64.1 months among the 49 patients. By the end of the follow-up, 41 of these patients were dead;the mean survival was 27 months. The 1-, 3-, and 5-year survival rate was 81.6%, 40.8%, and 20.4%, respectively. Univariate analysis identified that 6 variables were statistically significant prognostic factors of OS:with or without chemotherapy, ALP, previous skeletal-related event, Gleason score, PSA nadir, and time to castration resistance. The multivari-ate analysis showed that the time to castration resistance of ≥19 months and the addition of chemotherapy after disease progression are independent prognostic factors for a high OS. Conclusion:With or without chemotherapy and the time to castration resistance are the independent prognostic factors associated with survival in patients with prostate cancer accompanied by spinal metastases at first diagnosis.
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Objective:To investigate the safety and efficacy of laminectomy combined with vertebroplasty in spinal metastases from rapid-growth tumors. Methods:Clinical data of 23 patients with spinal metastases of lung cancer, who were admitted to the Cancer Hospital from July 2008 to May 2012, were retrospectively analyzed. Thirteen male and ten female patients, with an age range from 40 years to 65 years and a mean age of 51.5, were examined. All patients received posterior laminectomy to relieve spinal cord compression. Afterward, vertebroplasty combined with radiofrequency ablation was conducted, followed by the internal fixation of vertebrae (instrumental fixation). Operation time, blood loss, and bone cement leakage rate were analyzed. One month before and after the operation, pain measurement was conducted using visual analog scale (VAS) and neurologic deficit (spinal cord injury) by Frankel Grade. Functional impairment was classified by Karnofsky performance status (KPS) score. Quality of life was assessed by the European Organization for Research and Treatment questionnaire (EORTC QLQ-C30). Results:The mean operation time was 163±87.36 min. Blood boss was 430±130.35 mL. Bone cement leakage rate was 21.7%. One month before and after surgery, the VAS showed statistical significance (t=25.6, P<0.01). After surgery, 78.3%of all patients exhibited functionally satisfactory Frankel Grade D or E, compared with 43.5%of patients before the operation. KPS score (80 to 100) percentage was 69.6%after surgery compared with 34.8%before surgery. One month after the operation, remission of various degrees was seen in 10 of 18 patients who had sphincteric dysfunction before surgery (55.6%). The EORTC QLQ-C30 score was 85.39±8.99 before and 52.78±15.17 after operation. The quality of life improved significantly (t=11.6, P<0.01). Conclusion:Posterior laminectomy and vertebroplasty combined with radiofrequency ablation for spinal metastases from lung cancer is safe and effective. The treatment can improve pain, function, and life quality of patients with lung cancer spinal metastases.
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Objective To investigate the safety and efficacy of surgery in 121 patients with spinal metastases.Methotds A retrospective analysis of clinical data from April 2009 to March 2013 was performed in 121 patients with spinal metastases.From 37 to 65 years,69 males and 42 females with mean age of 55.6 years.Primary tumor origin:Lung 35(28.9％),Breast 26(21.4％),Renal 17 (14.0％),Prostate 20 (16.5％),Thyroid 14 (11.6％),Liver 2 (1.7％),Colon 1 (0.8％),other 6 (5.0％).All patients received surgery.Follow-up and survival time were analyzed.In preoperation and postoperative 3 month,pain levels were assessed by visual analogue scale (VAS),neurologic deficit was evaluated by Frankel Grade and functional impairment was classified by Karnofsky Score.The quality of the life was assessed by EORTC QLQ-C30 questionnaire.Survival analysis was evaluated by Kaplan-meier.Results The period of follow-up ranged from 5 to 35 months with the average of 15.9 months.The mean survival was 14.5 months.1-year survival was 53.5％.2-year survival was 36.5％.In patients with lung cancer,the mean survival was 8.5months.1-year survival was 14.3％.2-year survival was 11.4％.In patients with breast cancer,the mean survival was 31 months.1-year survival was 57.7％.2-year survival was 46.2％.In preoperation and postoperative 3 month,the VAS showed statistical significance (t=21.6,P＜0.01) ;Post-operatively,80.3％ of all patients had functionally useful Frankel Grade D or E compared with 43.5％ pre-operatively.KPS score (80-100) percentage was 75.6％ postoperatively compared with 33.4％ preoperatively.In 1month postoperatively,35 of 75 patients who were sphincteric dysfunction preoperatively were improved.The EORTC QLQ-C30score was 83.39±7.23 in preoperation and 51.34±14.27 in postoperaion.The quality of life was impoved significantly (t=12.6,P＜0.01).Conclusion Surgical treatment was effective in improving quality of life by providing better pain control,enabling patients to regain or maintain mobility,and offering improved sphincter control.In all patients,the number of patents with spinal metastases from breast and lung cancer is higher.Compared with spinal metastases from breast cancer,the proportion of lung cancer origin received surgery is higher.
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Objective To discuss the related factors of early pathological fracture after curettage of benign bone tumors in femoral shaft.Methods The clinical data of 47 patients with benign bone tumors in femoral shaft,treated by curettage with bone graft via the vastus lateralis approach from March 2004 to March 2011,were retrospectively analyzed.Thirteen patients of them presented with early pathological fracture after the curettage.In fracture group,there were 13 cases,11 males and 2 females,and the time from finishing curettage to fracture occurring ranged from 21 to 36 days.In non-fracture group,there were 34 cases,23 males and 11 females.The following data of fracture group and non-fracture group were compared and analyzed,such as specific value of absolute width of tumor and transverse diameter of bone shaft,specific value of defect width of bone window and sagittal diameter of bone shaft,defect length-width ratio of bone window,defect morphology of bone window,classification of bone tumor,violence of causing injury and compliance to medical advice.Results The average defect length-width ratio of bone window in fracture group was 3.72±3.58,in non-fracture group was 2.67±6.35.For classification of tumor,in fracture group 1 case was in incubation period,6 in active period,6 in invasion period; in non fracture group 21 cases were in incubation period,10 in active period,and 3 in invasion period.Four cases in fracture group had poor compliance to medical advice,and 9 in non-fracture group had good compliance.Between two groups,there were no statistical differences in specific value of absolute width of tumor and transverse diameter of bone shaft,specific value of defect width of bone window and sagittal diameter of bone shaft,and defect morphology of bone window.Conclusion When defect length-width ratio of bone window is larger than 4,the classification of tumor causes expanded incisal edge,and the cortical bone was damaged extensively,there are more possibilities for pathological fracture.
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ObjectiveTo investigate the safety and efficacy of combined treatment with subtotal corpectomy and radiofrequency ablation(RFA) for spinal metastases. MethodsFrom April 2009 to March 2010, 29 patients with spinal metastases who received subtotal corpectomy were analyzed. Sixteen patients (7 men and 9 women) with an average of 57.8 years having received subtotal corpectomy alone were selected for comparison (the subtotal corpectomy group). Thirteen patients (7 men and 6 women) with an average of 58.3 years having received subtotal corpectomy combined with RFA were chosen as subjects of this study (the RFA combination group). There were no significant differences between the two groups with respect to the patient's age, gender, and Tomita type. Pain levels pre-and post-procedure were assessed by the visual analogue scale(VAS), and neurologic deficit were evaluated by the Frankel scale. ResultsThe VAS in RFA combination group were 8.88±0.36, 3.76±0.33, 3.35±0.38 in preoperation, 1 month, and 6 months postoperatively, respectively. The VAS in subtotal corpectomy group were 8.96±0.39, 3.81 ±0.48, 3.41 ±0.42 in preoperation, 1 month, and 6 months postoperatively, respectively. The VAS in both groups showed statistical significance at each time point, there was no statistically difference between the two groups. The operate time in RFA combination group and subtotal corpectomy group were(216.54±113.77) min and(302.50±80.44)min, respectively. The blood loss of the two groups were (1084.62±539.82)ml and (1625.00±724.34)ml, respectively. The recurrent rate of the two groups were 30.8％ and 75.0％, respectively. The RFA combination group were lower in operate time, blood loss and recurrent rates than subtotal corpectomy group. Conclusion Compared with the subtotal corpectomy, the RFA combination can reduce the blood loss, operation time, and the recurrent rates.
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Objective To create a new animal model which can preferably simulate the human's scoliosis. Methods Forty-five 4-week-old female Wistar rats were randomly divided into 3 groups. Group 1 underwent subcutaneous left scapula-to-contralateral ilium tethering procedure with a non-absorbable suture,which made the spine convex towards right side, and then removed forelimbs and tails of rats to create the bipedal rats. Tethering sutures were cut at postoperative 8th week, and the spines of rats were then observed during 2 weeks. Group 2 were the same as group 1 but in which scapula-to-ipsilateral ilium tethering procedure was performed. Group 3 were the same as group 1 except that the bipedal rats were not created. All postoperative rats were fed separately in special high cages for group 1 and group 2 or in standard cages for group 3. Operative duration, postoperative first food-taking duration, operative mortality, body weight, relative length of the spinal cord, Cobb angles in the coronal and sagittal planes, modeling mortality, the incidences of re-operation, scoliosis and vertebral rotation among the 3 groups were compared. Results There were no significant differences in the degree of scoliosis or kyphosis among the 3 groups at the time of initial tethering. At 2 weeks after tether release, the incidence of vertebral rotation was significantly higher in group 1 than group 2 (86.7% vs. 33.3%), and the degree of scoliosis or kyphosis was significantly larger in group 1 than group 3 (coronal plane: 30.2°±10.4° vs. 20.5°±7.7°; sagittal plane: 55.6°±10.0° vs. 43.8°±6.3°). There was no significant difference in postoperative first food-taking duration among the 3 groups, and no death of rats occurred in all groups during intraoperative and postoperative 6 hours, although operative duration was significantly longer in group 1 or group 2 than group 3. There were no significant differences in body weight,relative length of the spinal cord, modeling mortality, the incidences of re-operation and scoliosis among the 3 groups. Conclusion The bevel and axial loads of the vertebrae can significantly enhance the incidence of vertebral rotation and the degree of kyphoscoliosis, respectively. The scoliosis model created by scapula-to-contralateral ilium tethering procedure in bipedal rats can preferably simulate the human's scoliosis.