Objective Create patient-derived xenograft (PDX) model of bone and soft tissue sarcoma,and analyze the success rate of PDX model,observe the effects of chemotherapy on PDX models and its coincidence,and provide a theoretical basis for screening sensitive second and third line drugs.Methods Collected 31 cases of bone and soft tissue sarcoma from January 2015 to May 2016,which included 12 male and 19 female,with an average age of (28.5±19.9) y.The tumor tissue was obtained the day of operation,and it was cut into 2 mm3 pieces and injected into the flank of BAL B/C nude mice or SCID mice.Tumor was passaged when the diameter reached 1-2 cm and the P0 tissue was froze.If there was no obvious tumor mass grows out for 3 months,the model creation will be stopped.We inoculated the mice with patients sample with or without chemotherapy,observed the effect of chemotherapy on the success rate of PDX modeling and the success rate of modeling of different pathological types,and also observed the relationship between the success rate of PDX modeling and the prognosis of patients.For the drug sensitivity test,3 mice was used in each group,and chemotherapy was given,T/C was used to evaluate the inhibition ratio after drug treatment.Results 31 PDX models were inoculated.The total success rate is 45.2％.Pathology of the PDX models and their success rates:24 osteosarcoma models,success rate is 37％;2 leiomyosarcoma models,success rate is 100％;2 chondrosarcoma models,success rate is 50％;1 Ewing sarcoma model successed;1 fibrosarcoma model and 1 synovial sarcoma model,were not successed.Post chemotherapy model success rate is 33％ (4/12),compared with 53％(10/19) of model success rate that without chemotherapy.And there is relationship between success rate of PDX model creation and patient outcome.The faster the PDX model creation,the worse the outcome.The drug sensitivity of PDX model coincides the clinical situation.Conclusion The success rate of creating PDX model of bone and soft tissue sarcoma is around 30％-40％,and it is related to the pathology and whether got chemotherapy or not,PDX models coincide sarcomas clinical situation,and it is hopefully to use PDX model in selecting personalized drugs.

Objective: This study was to investigate the effects of MEHP on isolated rat heart and explore its mechanism. Methods: The experiments were performed with Langendorff-perfused rat heart with a Langendorff apparatus. 35 SD rats were used in the experiment and there were 5 rats per group. MEHP at doses of 3.125, 6.250, 12.500 and 25.000 μmol/L were given to the hearts for 25 minutes. Effects of NAC at concentration of 5 mmol/L were evaluated by co-treatment with 12.500 or 25.000 μmol/L MEHP. Data was collected per 5 minutes for 25 minutes. The heart rate, LVDP, LVEDP, dp/dtmax, and dp/dtmin were measured and analyzed using a PL3508 Data Acquisition and Analysis System. 200 waves at least were required each time. LDH contents in heart lavage fluid were determined by photometric assays using the automated biochemical analyzer. A section of the heart tissue was used for histopathological examination. DCFH-DA method was used to detect the levels of reactive oxygen species in different groups of heart tissues. Results: There was a concentration dependent decrease of heart rate (P<0.05) . At concentrations of 6.250, 12.500 and 25.000 μmol/L, MEHP significantly decreased the LVDP, dp/dtmax and dp/dtmin (P<0.05) , and this decrease is more pronounced with perfusion time. As the MEHP was given up to 6.250, 12.500 and 25.000 μmol/L, a statistical significance was found in the increase of LVEDP (P<0.05) . For dp/dtmin, a significant increase was observed at the concentration of 3.125 μmol/L when perfused with 10 and 15 min (P<0.05) , but this increase disappeared over time. LDH in cardiac perfusate increased as the MEHP given a higher concentration (P<0.05) . Compared with the control group, Histopathological analysis showed edema of myocardial tissue and cells, and inflammatory cells infiltration and myocardial cells necrosis were obvious in the MEHP perfusion groups. Myocardial ROS levels of the four MEHP treatment groups were all significantly higher than that of control group (P<0.05) . These heart damage induced by MEHP could be attenuated by NAC in different degrees. Conclusion MEHP can induce damage to myocardial tissue of isolated rat heart and one possible mechanism is the oxidative stress

Objective:To investigate the effect of thoracolumbar osteoporotic vertebral compression fracture (OVCF) combined with lumbar degenerative spondylolisthesis (LDS) on spinopelvic sagittal parameters in the elderly.Methods:A case-control study was conducted to analyze the clinical data of 77 patients with thoracolumbar OVCF admitted to Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine from December 2016 to December 2021. There were 16 males and 61 females with the age of 61-92 years [(73.9±8.4)years]. All patients had single-level thoracolumbar fractures (T 11-L 2). Simple thoracolumbar OVCF was found in 49 patients (OVCF group) and thoracolumbar OVCF combined with LDS in 28 (OVCF+LDS group). The pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), lumbar lordosis (LL), thoracic kyphosis (TK), thoracolumbar kyphosis (TLK), sagittal vertical axis (SVA) and Roussouly types were detected and compared between the two groups before operation. Results:There was no significant difference in PT and SVA between the two groups (all P>0.05). The PI, SS, LL, TK and TLK in OVCF+LDS group were (55.8±11.0)°, (34.1±10.9)°, (45.7±9.1)°, (35.7±6.1)° and (24.8±5.2)°, significantly larger than (47.9±8.8)°, (27.0±9.4)°, (33.1±7.9)°, (29.5±6.2)° and (18.4±5.5)° in OVCF group (all P<0.01). Roussouly types I-IV counted 22, 16, 5 and 6 patients in OVCF group, compared to 8, 5, 6 and 9 patients in OVCF+LDS group ( P<0.05). Conclusions:Elderly patients with thoracolumbar OVCF combined with LDS can significantly alter spinopelvic sagittal parameters, and LDS may aggravate the thoracolumbar kyphosis of OVCF. To avoid sagittal imbalance, surgery should be performed as soon as possible.

Objective To investigate the effect of microglial derived extracellular vesicles on neuronal damage in the context of heat stress.Methods After BV2 microglial cells were exposed to heat stress,the supernatant was collected and subjected to ultracentrifugation at different speeds to obtain large and small vesicles,respectively.Nano Particle Tracking and Zeta Potential Distribution Analyzer was used to measure and analyze the size distribution of the large vesicles and small vesicles.Western blotting was used to detect the expression of specific vesicle surface markers,TSG101,CD63 and flotillin-1.Microglial extracellular vesicles were labeled with PKH67 dye and then co-cultured with N2a cells to examine the uptake by capacity the neurons.After large and small vesicles derived from microglia after heat stress stimulation were co-cultured with N2a cells,respectively,CCK-8 assay,lactate dehydrogenase (LDH)assay,Trypan blue staining and TUNEL assay were employed to evaluate heat stress induced neuronal damage.Results The small vesicles were in a particle size of 30～120 nm,and highly expressed TSG101 and CD63,whereas the large vesicles,in a size of 90～1000 nm,highly expressed flotillin-1.The BV2-derived extracellular vesicles could be taken up by N2a cells and were proved to be involved in the modulation of N2a cell injury caused by heat stress.CCK-8 assay showed that both large and small vesicles of microglial cells inhibited the viability of N2a cells after heat exposure (P<0.05).The results of LDH assay,Trypan blue staining and TUNEL assay showed that both large (P<0.05)and small vesicles (P<0.01)significantly enhanced the LDH release,blue stain intensity and apoptosis of N2a cells after heat exposure,and the release,intensity and apoptosis were stronger in the cells treated with small vesicles than those group of large vesicles.Conclusion Microglia aggravate heat stress-induced neuronal damage through releasing extracellular vesicles.