Because of their ability to inhibit osteoclast-mediated bone destruction,bisphosphonates are widely used in the treatment of malignant bone diseases.Recent preclinical evidence shows that bisphosphonates not only exert direct anti-tumor effects but also have anti-angiogenic properties.And furthermore,they may act synergistically with other chemotherapeutics or T cells on tumors.These new findings are ushering in the possible application of bisphosphonates as anti-tumor therapeutics in clinical practice.

BACKGROUND: Obesity has become the most common and costly metabolic problem in the world, and the genetic and environmental effects on the generation of obesity have become one of the focus factors in obesity research. Gene-chips have been reported as a useful tool in human adipose tissue research. OBJECTIVE: To determine the peripheral blood gene expression profile of Chinese adult obesities by gene chip technique for the first time. DESIGN: Randomized controlled observation. SETTING: Beijing University of Traditional Chinese Medicine. PARTICIPANTS: The experiment was performed at the Basic Medical College of Beijing University of Traditional Chinese Medicine between August 2003 and May 2004. Five obese patients, 4 males and 1 female, aged (21.4±0.9) years and three non-obese persons, 2 males and 1 female, aged (26.0±5.3) years were selected by the international body mass index (BMI) standard. The written informed consent was obtained from all subjects, and the research was approved by the medical ethical committee of Beijing University of Traditional Chinese Medicine. METHODS: Total RNA was extracted from peripheral blood, amplified and labeled. The quality and quantity of the processed samples were checked by Test3 array. The gene expression profiles were monitored by U133A set. The data was analyzed statistically, and the gene symbols with significant difference were searched in Gene BANK database. MAIN OUTCOME MEASURES: Gene expression signal. RESULTS: Compared with non-obese adults, 66 genes showed up-regulated expression and 28 genes showed down-regulated, of which 11 genes were up-regulated above twofold, and 6 genes were down-regulated above twofold. The results demonstrated that HLA-DQAI (human leucocytic antigens), CRAT, MAPKSI3 and DKFZP434N1923 genes were up-regulated above 4 fold, and HLA-DQA1 gene was even up-regulated above 20 fold. CONCLUSION: Significant differences in peripheral blood gene expression profiles in Chinese adult obesities are found for the first time. The results indicate that obesity is strongly associated with MHC class II antigen HLA-DQA1, and HLA-DQB 1, etc.

[Objective] To explore the possible interest of therapeutic approaches including nitrogen-containing biphosphonate zoledronic acid using osteosarcoma cell lines MG63,and to investigate whether there is a synergism between zoledronic acid and methotrexate.[Method]Zoledronic acid alone or combined with methotrexate was used to treat human ostoesarcoma cells line MG63.The cell growth inhibition was assessed by MTT.[Result]There was a dose-dependent and time-dependent(1-100?mol/L)inhibition of cell proliferation by zoledronic acid.IC50 value of zoledronic acid for therapy of MG63 after 72h was 9.39 ?mol/L.The cell growth inhibition rates of MG63 at 72 h was 48.95% in zoledronic acid(10 ?mol/L)group,and 37.68%,45.93% and 52.42% in methotrexate groups MTX(1,10 and 100 mg/L).When combined treatment of zoledronic acid(10?mol/L)and methotrexate(1,10 and 100 mg/L)was used,the cell growth inhibition rates were 51.96%,66.77% and 69.23%,respectively.The combination of zoledronic acid and methotrexate demonstrated a synergistic effect.The differences were significant(P

Objective To analyze the medium and long-term results of tricuspid valve replacement (TVR)and summarize the operative experience for tricuspid valve disease.Methods Clinical data of 27 patients with severe tricuspid valve disease from September 2005 to May 2010 were retrospectively reviewed.Biological valve prosthesis was replaced in 23 patients,while mechanical valve prosthesis was replaced in 4 patients.Accompanying procedures included mitral valve replacement in 8 cases,mitral valve replacement and aortic valve replacement in 4 cases,and repair of atrial septal defect in 4 cases.Results The operative mortality was 11.1％(3/27),among these patients,2 cases died of serious low cardiac output syndrome,1case died of muhiorgan failure on the 7th day after operation,1 case who underwent reoperation for hemorrhage postoperative was improved after treatment.During follow-up,1 patient died of biological valve prosthesis dysfuncion 3 years after operation,1 patient died of cerebral embolism 19 months after operation.Six cases were in New York Heart Association(NYHA)class Ⅰ,and 14 cases in NYHA class Ⅱ during the period of follow-up.Conclusions Because operative and follow-up mortality is high,TVR is the last selection for the treatment of tricuspid valve disease.Appropriate operative technique and perioperative therapy are the key for clinical success.For those older than 50 years,follow-up inconvenience and reproductive-age female patients,biological valve prosthesis should be recommended as a preferential choice.

AIM: To study the effects of recombinant soluble MHC class Ⅰ chain-related protein A (sMICA) on the cytotoxicity, secretion of IFN-γ, proliferation and apoptosis of peripheral NK cells. METHODS: After NK cells were cocultured with recombinant soluble MICA proteins overnight, the cytotoxicity of NK cell on target cells was detected by flow cytometry. The supemant was collected to determine the concentration of IFN-γ by ELISA. The proliferation of NK cells to sMICA was detected by MTS/PMS. NK cells were labeled with annexin V and PI to analyze their apoptosis. RESULTS: Soluble MICA inhibited the cytotoxicity of NK cells and down-regulated the secretion of IFN-γ, but it showed no effects on the proliferation and apoptosis of freshly isolated peripheral NK cells. CONCLUSION: The soluble MICA shedding from tumor cells could be a pathway of cancer immune evasion by down-regulating the biologic activities of NK cells.

Objective: To observe the effect of ZuoGuiWan and YouGuiWan on induced experimental autoimmune encephalomyelitis(EAE) in Lewis rats,compare the therapeutic effect between ZuoGuiWan and YouGuiWan,and explore the underlying immunoregulatory mechanism between warming-yang and nourishing-yin therapy.Methods : 120 male Lewis rats were bred at Capital Medical University under specifi c pathogen-free conditions.24 rats were selected as normal group before immunization.The other rats were randomly devided into 4 groups after immunization,including EAE group,prednisone group,ZuoGuiWan group and YouGuiWan group.Rats of normal group were injected with normal sodium in the hind feet pad on both sides,the other rats were injected with the antigen consisted of myelin basic protein(MBP) and complete Freund’s adjuvant(CFA) to induce EAE.Rats of normal group and EAE group were administered with normal sodium after immunization,rats of prednisone group with prednisone(5mg/kg),rats of ZuoGuiWan group with ZuoGuiWan(2g/kg),rats of YouGuiWan group with YouGuiWan(3g/kg).On the day 15 and 27 after immunization,the peripheral blood was collected,lymphocyte subgroups and NK cells were detected by ? ow cytometer.Results: On day 15 after immunization: In peripheral blood,the number of CD4+lymphocyte in ZuoGuiWan group was signifi cantly higher(P

Objective: To observe the immunohistochemical expression of interferon-? (IFN-?), matrix metalloproteinase -9(MMP-9) in brain and spinal cord tissue, and explore the action mechanism of Zuogui Pills and Yougui Pills on rats with experimental autoimmune encephalomyelitis(EAE). Methods: Lewis rats were immunized with the myelin basic protein (MBP).120 Rats were grouped randomly into nomal group, EAE group, prednisone group, Zuogui Pills group and Yougui Pills group after post immunization (PI). Rats in normal group and EAE group were administered sodium, each 3ml/d, rats in prednisone-group were administered suspension of prednisone after developed clinical signs, each 5mg/kg, rats in Zuogui Pills group were administered suspension of Zuogui Pills, each 2g/kg, and rats in Yougui Pills group were administered suspension of Yougui Pills each 3g/kg. On days 15 and 27 PI, rats were killed and the immunohistochemical staining was performed on the sections of brain and spinal cord. Results: On days 15 and 27 PI, the expression of IFN-? and MMP-9 in central nervous system of EAE group were higher than those in nomal group (P

ObjectiveTo investigate the myocardial protection on cardiac valve replacement surgery with creatine phosphate of myocardial GIK (GIK) in order to reduce the surgical risk and improving the efficacy.Methods126 cases were unergone surgical treatment of heart valve disease,whose cardiac function on admission wereⅢor Ⅳ. 126 patients were randomly divided into two groups. Cardiopulmonary bypass time, aortic cross clamp time, postoperative myocardial injury markers ( CK-MB, cTNI) changes, arrhythmias, heart function recovery, length of stay and mortality rate and other indicators were compared between the two groups. ResultsThe age, gender, body mass,heart disease and surgery combined data were not statistically significant between the two groups( all P ＞0. 05). The cardiopulmonary bypass time, aortic cross clamp time and mortality had no significant differences between the two groups( all P ＞ 0.05 ). The CK-MB( 21.36± 9.21 ) U/L and cTNI(0.83 ± 0. 35 ) ng/ml of creatine phosphate group were significantly lower than those of the control group. The incidence of arrhythmia in phosphocreatine group (37. 1％ ) was significantly lower than ordinary group (57.8 ％ ) ( X2 ＝ 5. 418, P ＜ 0. 05 ). ConclusionThe application of creatine phosphate GIK before valve replacement surgery could effectively reduce reperfusion injury after myocardial ischemia,myocardial protection,and significantly reduce the incidence of arrhythmia and improve heart function in patients.

Objective To summarize the results of valve re-operative cases after cardiac valve replacement, to find the better re-operative time, and to estimate the re-operative methods and influencing factors of the operation. Methods Thirteen valve re-operative cases after cardiac valve replacement from October 2008 to February 2010 were retrospectively studied. According to NYHA classification, 9 cases belonged to class Ⅳ, and only 4 cases belonged to class Ⅲ preoperatively. Mitral valve replacement (MVR)was performed in 7 cases, aortic valve replacement (AVR) in 3 cases, MVR + AVR in 3 cases. Results The early-stage postoperative mortality was 7.7%( 1/13),and the reason was low cardiac output syndrome. Two cases who underwent re-operation and re-intubation respectively after operation for hemorrhage were improved after treatment. Twelve cases were discharged in 3-6 weeks after heart valve surgery and all were followed up for 6-15 months. The cardiac function of all the discharged patients recovered well and no death occurred during follow-up. Conclusion The key factors to reduce the death of re-operation are improving preoperative heart function,setting up extracorporeal circulation as soon as possible,consummating myocardial preservation,perfecting operating skills,correcting low cardiac output syndrome in time and preventing complications.

Objective To evaluate the PSD-007-mediated photodynamic effect on mouse osteosarcoma cell line LM-8, both in vitro and in vivo. Methods LM-8 cells were incubated with different concentrations of PSD-007 for 4 hours and then followed different laser irradiations. After photodynamic therapy (PDT), cell viability was measured using MTT assay and the optical density in each experiment was measured at 450 nm with a micro plate reader. The inhibition rate of cell growth was calculated. Four-week-old female C3H mice were used for implantation of LM-8 cells. When the diameter of tumor reached up to 7-8 mm, the mice were randomly divided into following groups: 1) control group, including untreated control, saline with laser irradiation, PSD-007 without laser irradiation; 2) PDT group, PSD-007 (5 and 10 mg/kg) was injected intravenously into the mice, and the tumor site was irradiated with laser light 6 hours after injection. Seven days after PDT, the size and weight of the tumors were measured. The inhibition rate of tumor was calculated, and all tumor specimens were taken for pathologic examination. After the diameter of tumor was 10-12 mm, the tumors were performed a marginal resection and subsequently followed 3 different treatments: without PDT (control), PDT with 240 J/cm2 or 360 J/cm2 laser irradiation. After 4 weeks treatment, the tumor recurrence rates were analyzed. Results MTT assay revealed that the cytotoxic effect of PDT on the LM-8 cells was positively correlated with the concentration of PSD-007 and the level of laser irradiation. When the concentration exceeded 4μg/ml, and the energy exceeded 6 J/cm2, the inhibition ratio was over 50%. No anti-tumor effect was observed in the cells treated with only laser irradiation or PSD-007 injection. Compared with the control group, the size and weight of the tumors were obviously decreased after PDT. PDT performed after marginal resection of the tumor reduced the rate of local recurrence. Conclusion PDT with PSD-007 showed cytotoxic effect on the LM-8 cells, and which performed after marginal resection of the tumor reduced the rate of local recurrence.