Hypoxia results from long-term anti-angiogenic therapy and can stimulate hypoxia-inducible factors (HIFs). HIF-induced hy-poxia signaling is involved in various steps in tumor invasive-metastatic cascade. On the one hand, HIFs regulate epithelial-mesenchy-mal transition. On the other hand, the characteristics of pericytes around vessels and the links among endothelial cells can change;thus, tumor cells can more easily intravasate into blood vessels, survive in peripheral blood, and then reach specific organs, ultimately resulting in metastasis. This review discusses the emerging mechanisms of long-term anti-angiogenic therapy and the occurrence of metastasis.

Objective To investigate incidence,risk factors and the prevention strategy of local recurrence 6 months after surgery for metastatic bone tumors.Methods Data of 797 patients who had undergone operations for metastatic bone tumors from March 1997 to March 2012 were retrospectively analyzed.Sixty-three patients (7.9％) who had local recurrence 6 months after operation were enrolled in the recurrence group,including 40 males and 23 females,and the average age at the time of operation was 55.21 years.Seven hundred thirty-four patients were enrolled in the non-recurrence group,including 432 males and 302 females,with an average age of 56.49 years.The risk factors for local recurrence 6 months after operation for metastatic bone tumors were statistically analyzed.Results The statistical analysis showed the risk factors for local tumor recurrence 6 months after surgery for metastatic bone tumors included preoperative general condition (10.9％ vs 6.2％),the rate of progress of the primary tumor (10.1％ vs 6.1％),site of bone metastasis (9.1％ vs 3.9％),surgical method (11.4％ vs 6.4％),whether local radiotherapy was performed preoperatively (28.0％ vs 6.6％),whether local radiotherapy was performed postoperatively (8.7％ vs 2.8％),whether sensitive systemic therapy was performed preoperatively (12.2％ vs 6.1％),whether sensitive systemic therapy was performed postoperatively (10.3％ vs 5.6％) and whether local therapy was performed in primary tumor site (10.1％ vs 5.8％).Multivariate analysis showed the independent risk factors included preoperative general condition (OR=0.534),rate of progress of the primary tumor (OR=2.164),site of bone metastasis (OR=2.906),whether local radiotherapy was performed preoperatively (OR=3.184),whether sensitive systemic therapy was performed preoperatively (OR=2.344) and whether sensitive systemic therapy was performed postoperatively (OR =0.468).Conclusion When the patients has following conditions:poor preoperative general condition,fast progressive primary tumor,metastatic tumor in the axial skeleton,application of local radiotherapy preoperatively,and application of sensitive systemic therapy,the surgical treatment should be chosen cautiously.

Dedifferentiated chondrosarcoma(DDCS)comprises approximately 10%of all chondrosarcomas and has the worst outcome with a 5-year survival of 10%.The preferred localizations are the femur,humerus and pelvis.DDCS represents a special form of chondrosarcoma characterized by the presence of well-differentiated cartilaginous component in juxtaposition with malignant mesenchymal tumor of high-malignancy grade.The diagnosis of DDCS is highly complicated,requiring detailed radiological and histopathological evaluation as well as precise bioptic technique.The dedifferentiated component is typically a high-grade sarcoma(usually grade 3 or 4),which can be either an osteosarcoma,a malignant fibrous histiocytoma or an anaplastic spindle cell sarcoma.In approximately one-third of the radiographs,one-third of the MR images,and one-half of the CT scans, the tumors demonskates bimorphic features.Recently,array-based comparative genomic hybridization(array-CGH)studies have been performed on frozen chondrosarcoma(including DDCS)specimens.There is a statistically significant association between high-grade tumor(grade Ⅲ and dedifferent ated)and the recurrent genetic deletions at 5q14.2～q21.3,6q16～q25.3,9p24.2～q12,and 9p21.3.One of the most commonly deleted regions of DDCS involved chromosome 9.Earlier investigations of DDCS showed p53 mutation and p53-LOH in the anaplastic component.It is also accompanied by Rt-LOH.P161NK4 and E-cadherin promotor methylation were observed in the low grade chondroid compartment of DDCS.While p161NK4,FHIT,and E-cadherin were methylated in highly malignant osteosarcomatous compartment of the tumor.Surgical resection of the tumor within wide or radical margins is the most important treatment.The value of neoadjuvant or adjuvant therapy remain uncertain.Several new drug targets have been identified and phase Ⅱ studies are currently ongoing.Current phase Ⅱ trials open for DDCS patients used the following medicine:apomab(proapoptotic selective agonist of Ap02L/TRAIL death receptor),perifosine(serine/threonine kinase Akt inhibitor),dasatinib(multitargeted small-molecule tyrosine kinase inhibitor),and the combination of gemcitabine and docetaxel.More recently,several phase Ⅰ studies have reported incidental responses of DDCS to newer targeted agents,such as histone deacetylase and vascular endothelial growth factor antisense oligodeoxynucleotide.The prognosis for patients with DDCS remains poor. The poor prognosis of the DDCS is determined by nonchondroid high grade component caused by invasive growth and formation of metastases.Therefore,early diagnosis and prompt surgical treatment may improve the outcome.

Objective:To clarify the effects of the BMP receptor inhibitor LDN-193189 in the dedifferentiated chondrosarcoma (DDCS) cell line NDCS-1 and to explore the anti-tumor mechanism of LDN-193189 in DDCS. Methods:NDCS-1 was treated with 5 nmol/L of LDN-193189. MTT assay and clone formation experiments were used to verify that LDN-193189 suppressed cel proliferation. Transwel and wound healing tests were performed to demonstrate that LDN-193189 inhibited cell invasion. Western blot detection was used to show that LDN-193189 inhibited the suppression of BMPR2, p-Smad1/5, and RUNX2 protein expression. Results:The BMPR2 signaling pathway was inhibited by LDN-193189;thus, cell viability and invasion were significantly suppressed. Conclusion:LDN-193189 induces the inhibition of progression in vitro via the BMPR2-p-Smad1/5-RUNX2 signaling pathway in the human DDCS cell line NDCS-1.

Objective To discuss the effect of polysaccharides from Tegillarca granosa as an adjuvant on pcDNA3.1?Sj26GST vaccine against Schistosoma japonicum infection. Methods Sixty SPF BALB/c mice were divided into four groups randomly(15 mice each group),including a control group,a polysaccharides group,a vaccine group,and a vaccine plus poly?saccharides group. In the 0,2th and 4th week of the experiment,the mice in the above four groups were immunized for 3 times with 100μl PBS,100μg polysaccharides from Tegillarca granosa,100μg Sj26GST vaccine,and 100μg Sj26GST vaccine plus equivalent polysaccharides,respectively. Two weeks after the last immunization,all the mice were infected with 40 ± 1 Schistosoma japonicum cercariae through the skin of the abdomen. After the infection for 6 weeks,all the mice were sacrificed, and their serums,livers and the adult worm of Schistosoma japonicum in them were collected,the specific sera IgG antibodies were detected by ELISA,and the worm reduction rates and egg reduction rates in the liver were calculated. Results Six weeks after the infection,the IgG antibody levels of the mice in the vaccine group and the vaccine plus polysaccharides group were 18.26 ± 0.42 mg/ml and 20.21 ± 0.89 mg/ml respectively,the difference between them were statistically significant,and both of the IgG levels of the above groups were significantly higher than those in the control(both P<0.05). The worm reduction rate and egg reduction rate in the vaccine group were 28.60%and 35.84%,respectively,and the rates in the vaccine plus polysac?charides group were 38.04% and 49.74%,respectively,the differences between the worm reduction rates and egg reduction rates were both statistically significant(both P<0.05). Meanwhile,the two rates in the two above groups were all significantly higher than those in the control group(all P<0.01). Conclusion Polysaccharides from Tegillarca granosa using as an adju?vant can increase the protection effect of pcDNA3.1?Sj26GST vaccine against Schistosoma japonicum infection.

Primary immunodeficiency disease (PID) are rare diseases caused by inherent defects of the immune system,the main clinical manifestations are increased susceptibility to infections,autoimmune diseases and malignancies.For such rare diseases,it's essential to establish national patient online database for collaborative studies.By using hypertext preprocessor (PHP) and MySQL,the database and registration system are successfully set up,and itcould complete inquiries for the information saving,export,query,retrieval,backup etc.This database includes patient's information on the diagnosis,clinical manifestations,laboratory examinations,treatments.Through communication and information-sharing between multiple centers,it creates a basis for nationwide research on PID.

The development and progression of tumors are closely related to the tumor microenvironment.As one of the most important com-ponents in tumor microenvironment,cancer-associated fibroblasts (CAFs)play an important role in carcinogenesis,angiogenesis,inva-sion,and metastasis of tumors.The role of CAFs in the development and progression of hepatocellular carcinoma (HCC)is reviewed by dis-cussing how CAFs are recruited and activated in the tumor microenvironment and how CAFs promote tumor angiogenesis and regulate tumor immunity.This review may provide new approaches for the treatment of HCC.

[Objective]To evaluate the outcome on patients with primary infection of intervertebral space of the thoracolumbar spine following combined one-stage debridement,strut grafting and internal fixation.[Method] From May 1999 to February 2006,18 patients with spontaneous infection of intervertebral space were analyzed retrospectively.These infections occurred at thoracic spine in 3 cases(16.7%),thoracolumbar junction in 2 cases(11.1%),lumbar spine in 10 cases(55.5%),and lumbosacral junction in 3 cases (16.7%).Their clinical data and outcome were studied.None of all had previous spinal surgery or spinal injection,and their diagnosis were confirmed by histopathology after surgery.All patients were treated by one-stage debridement,strut grafting and internal fixation after failure of nonsurgical treatment.Antibiotics was used following debridement in the infection sites,and was continued to be administered after surgery.Patients were evaluated before and after surgery in terms of pain,neurologic level,sagittal spinal balance,and radiologic fusion.[Result]Postoperatively,all patients experienced significant relief of symptoms,and no fever.Six patients showed improved neurological status(at least one grade improvement on Frankel's functional classification).Only 3 of 18 cases had a positive culture result that pathogen identified Staphylococcus aureus.Histological examination of the specimen after surgery revealed that inflammation occurred in all patients,but no evidence of tuberculosis.The period of follow-up ranged 13 to 45 months with a mean of 26 months.No evidence of recurrence or residual infection was observed in any patient.Postoperative radiological evaluation revealed that implants were stable,there was no phenomena of prosthesis subsidence,hook dislodgment and failure restoration of spinal segments height.Solid bony fusion was obtained in all patients.Eight patients were misdiagnosed for spinal tuberculosis.[Conclusion] One-stage eradication of the infection,strut grafting and internal fixation are effective treatments for primary infection of intervertebral space.The presence of the instrumentations at the site of infection has no negative influence on the course of infection healing.

[Objective]To evaluate the diagnostic strategy for bone metastasis from unknown primary. [Method]One hundred and twenty five patients with unknown primary bone metastasis were treated from June 2003 and December 2006.The distribution of bone metastasis while initial diagnosis mainly focused on spine,sacrum,pelvis,femur and humerus.The diagnostic strategy contained a series of physical examination,laboratory test,imaging study and pathological examination.[Result]The primary tumor was found in 70.4% cases,while 40% was in the lung,8% in kidney,5.6% in prostate,4.8% in liver,4% in breast,both 2.4% in thyroid and gastric,and 3.2% in other visceras.The physical examination revealed the occult primary site of the malignant tumor in only 9.6% cases.Although,43.2% patients had higher level of tumor antigen,but most of them were non-specific.Sixty percent of primary tumor was found by various imaging studies including plain radiograph,computed tomography and ultrasound.The pathological result after biopsy or operation identified or suggested the primary tumor in 66.4% cases.The one year survival rates after diagnosis were 58.57% and 22.93% in patients of bone metastasis with known and unknown origin,respectively.[Conclusion]The primary tumor can be diagnosed in most bone metastasis patients with no cancer history after careful examination,and patients will get benefit on survival time for targeted treatment.

Objective:Research on establishing a better experimental arthritis rat model of cold-dampness arthraligia on rheumatoid arthritis(RA) research.Methods:In order to induce arthritis,the rat's feet were injected with different concentrations of type Ⅱ collagen mixed with Freund's adjuvant;measure the feet swelling degrees of rats,then calculated swelling rate;detect the level of serum sialic acid(SA);observ the synovial histopathology and ultrastructural of rats.Results:The rat joints swell of the group with low concentration of type Ⅱ collagen and completed Freund's adjuvant was rapid and severe,while that of the group with high concentration of type Ⅱ collagen and incompleted Freund's adjuvant was moderate and lasting.The level of serum SA of model groups was higher than the normal group.The histopathology changes of rat's synovium conform to RA.Conclusion:The group injected with high concentration of type Ⅱ collagen and incompleted Freund's adjuvant is the ideal RA model.It is belonged to the symptom of cold-dampness arthralgia,compared with this model,the AA approaches the symptom of heat-dampness arthralgia.