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 clinical effects of intensive insulin therapy on postoperative infection, inflammatory response and prognosis in the non-diabetic patients of different ages undergoing coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). Methods 60 cases of non-diabetic patients (>60) undergoing coronary artery bypass grafting with cardiopulmonary bypass between June 2005～June 2010 were selected and analyzed retrospectively. 60 patients were divided into 2 groups, the previous 24 cases were included in a routine treatment group and later 36 cases were included in the intensive therapy group. The blood sugar of intensive therapy group was strictly controlled starting from the anesthesia. The routine treatment group was controlled starting from backing to ICU according to blood glucose results. Patients were assigned to the routine therapy group with the blood glucose maintained at 10.0～11.1 mmol/L and the intensive therapy group received tight glycemic control with the target blood glucose maintained at 4.4～6.1 mmol/L. Postoperative infection, mechanical ventilation time, hospital stay and mortality indicators were compared between the 2 groups. Results There were no significant difference (P＞0.05) in gender, body weight, disease diagnosis and combined surgical methods and surgical materials such as cardiopulmonary bypass time between the 2 groups. Neutrophil count［(12.6±2.8)×109/L vs (18.8±3.1)×109/L］, blood infections, respiratory tract infection(6/36 vs 10/24) and wound infectionrates(2/36 vs 6/24) and other indicators of intensive of insulin therapy group were lower than the regular therapy group (P＜0.05). The postoperative hospital stay of intensive therapy group［(12.2±3.7)d vs (15.6±5.4)d)］ was statistically significant shorter compared with the conventional treatment group (P＜0.05). There was no significant difference in postoperative mortality between the 2 groups (P＞0.05). Conclusions Intensive insulin therapy may significantly reduce postoperative infection rate in the old age patients, thus leading to an improved prognosis in the non-diabetic patients undergoing coronary artery bypass grafting with cardiopulmonary bypass.

ObjectiveTo explore the surgical treatment of congenital heart disease combined with severe pulmonary hypertension.MethodsThirty-two patients of congenital heart disease combined with severe pulmonary hypertension were included in the study.The saturation of arterial oxygen ranged from 0.84 to 0.94 and echocardiography showed left to right slow velocity shunt in 20 eases,double direction shunt in 10 cases and no shunt in 2 cases.The pulmonary arterial pressure was 65-120 (82 ± 14) mm Hg ( 1 mm Hg =0.133 kPa).All patients received surgical repairs under cardiopulmonary bypass and were treated preoperatively with oxygen inhalation therapy,oral intake of beraprost sodium or silaenafil respectively according to the degree of pulmonary hypertension.During cardiopulmonary bypass,pulmonary artery perfusion was performed with protective solution containing ulinastatin for lung protection.Vasoactive drugs were routinely administrated postoperatively.Results Thirty-two cases underwent the surgical treatment successfully with their postoperative pulmonary arterial pressure decreased 20 -40 mm Hg and 2 cases died of severe low cardiac output syndrome and fatal arrhythmia.The mortality was 6.25％(2/32).ConclusionComprehensive perioperative management followed by radical operation can achieve a good clinical result on congenital heart disease combined with pulmonary hypertension.

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.

Objective To investigate the improvement of ischemic hypoxic injury of brain after the transplantation of bone marrow mesenchymal stem cells (BMSCs).Methods Rats were randomly (random number) divided into sham operation group,cardiac arrest group and BMSCs treatment group (n =10 in each group).The model of cardiac arrest was induced by asphyxia.One hour after restoration of spontaneous circulation (ROSC),green fluorescent protein labeled BMSCs were transplanted via tail vein injection.At 3 and 7 days after transplantation,frozen sections of hippocampus was stained with hematoxylin-eosin (HE).The rest of brain tissue was weighed by an electronic balance.Brain water content (％) was calculated as (wet weight-dry weight) / wet weight × 100％.Results ①BMSCs were observed in hippocampus at 3 and 7 days after transplantation under fluorescent microscopy.②Compared with sham operation group and BMSCs treatment group,brain water content in cardiac arrest group was higher (all P ＜ 0.05).HE staining results showed that BMSCs transplantation could lessen hypoxia ischemia damage on brain.Conclusions BMSCs reduced the neurons damage induced by cardiac arrest and promoted neurological function recovery.