PurposeTo investigate the mechanism of BM210955 (ibandronate, a new bisphosphonate drug manufactured in China)in the prevention of bone loss in vitro. MethodsThe osteoclasts isolated from the long bone of 10-day-old Rabbit were cultured on glass and bone slices in different concentration of BM210955. TRAP(tartrate resistant acid phosphonase) staining for osteoclast and TB( toluidine blue)staining for resorption lacunae were used on bone slices and Fluorescence (orange acridine) staining for apoptosis cell on glass slices was used;Multinucleated( three and more nuclei) TRAP positive cell and Apoptosis cell and Pits were counted. ResultsThe BM210955 decreased the multinucleated cell number by 73% in 10-8 mol/ L;The inhibitory rate of pit formed was correlate to concentration as 31.58%, 76.32% and 87.99% to 10-12, 10-10 and 10-8 mol/L; The apoptosis induction was shown in above 10-8 mol/L, and the apoptosis rate was 62% in 10-4 mol/L. Conclusions Induction of osteoclast apoptosis and decrease of the cell number and inhibition of resorptive ability were the major mechanism for bone loss prevention effect of BM210955 in vitro.

Human osteoblasts from donors of different age (≤5, 30-40, 50-60, ≥70) groups were isolated and cultured. Osteoprotegerin (OPG) and osteoclast differentiation factor (ODF) mRNA expressions were assayed by RT-PCR when the osteoblasts in the second passage were cultured for 14 days. Results showed that human osteoblasts from different age groups expressed OPG and ODF mRNA. Quantity of OPG mRNA and ODF mRNA expressions was correlated to donor′s age.

BACKGROUND: Revascularization of trachea following trachea transplantation needs to be solved.OBJECTIVE: To explore the empirical methods of allogeneil graft of long-segment trachea and its revascularization.DESIGN, TIME AND SETTING: The animal observation experiment was performed at the Department of Chest Surgery, Shandong Provincial Chest Hospital between June 2007 and June 2008.MATERIALS: Totally 20 healthy, New Zealand rabbits, were provided by animal center of Medical School of Shandong University. Additional 10 rabbits were used as donors, and 10 rabbits were served as recipients.METHODS: The mucosa and smooth muscle in trachea of donor rabbits was removed, and the anular ligaments were shear opened or intensive drilling to obtain tracheal cartilage scaffold with fissure or mesh. A jejunum with vascular pedicle was harvested from recipient rabbits, which was longer than tracheal cartilage scaffold. The cartilages rings were wrapped with greater omentum. Finally, the constructed simulating trachea was replaced in the abdominal cavity. MAIN OUTCOME MEASURES: Growth of retina and tracheal cartilage.RESULTS: Abdominal cavity of recipient rabbit was opened after 2 weeks, and it was observed with gross observation and pathological section: There was no collapse in the lumens of tracheal allografts with good elasticity tracheal wall. The blood of omentum and intestinalmucosa that wrapped tracheal allograft was circulating well; and there was no cellular necrosis and merging in xenogenic cartilagines tracheales. CONCLUSION: The study fulfilled the stage one reconstruction and revascularization of tracheal allograft in abdominal cavity of recipient. Stenopeic tracheal stand wrapped with pedicled omentum and intestinalmucosa of recipient made allograft not restricted by length, which is critical to revascularization of long-segment trachea.

BACKGROUND: Diphosphonate has a predominant therapeutic effect in the prevention and treatment of postmenopausal osteoporosis. Ibandronate, as a new-type diphosphonate preparation, is gradually becoming a study hotspot.OBJECTIVE: This study is to investigate the efficiency of ibandronate in interfering postmenopausal osteoposis by observing bone mass loss related indexes in ovariectomized rats, and made a comparison with nilestriol.DESIGN: A completely randomized grouping, and controlled animal experiment.SETTING: Study Room for Bone metabolism, Fudan University Medical College.MATERIALS: Forty SD female rats, aged 10-12 months, were involved in this study. Ibandronate was provided by the State Key Laboratory of Jiangsu Institute of Atomic Medicine. Nilestriol was produced in the Shanghai 12th Pharmaceutical Factory.METHODS: This experiment was carried out in the Study Room for Bone Metabolism, Institute of Radiation Medicine,Shanghai Medical University between August 1996 and June 1998. The rats were divided into 4 groups by a lot, 10 rats in each: sham-operation group, ovariectomized group, ovariectomized+ibandronate group and ovariectomized +nilestriol group. In the sham-operation group, only small pieces of adipose tissue around the ovary were resected from the rats.Three months after operation, each rat was intragastrically administrated with 1 mL normal saline; In the ovariectomized group, ovariectomized+ibandronate group and ovariectomized +nilestriol group, each rat was subjected to bilateral ovariectomy, and 3 months later, they were intragastrically administrated with normal saline, ibandronate water solution [0.5 mg/( kg·d)] and nilestriol suspension [1 mg/(kg· time)] respectively. Each rat in the latter three groups was administrated for 90 days, twice in the first week, and then once a week.MAIN OUTCOME MEASURES: Left femur was taken out, and its dry weight and ash weight were measured. Calcium content of bone was determined with an atomic absorption spectrophotometer, bone density of the whole body with a bone density apparatus, the bone density at the juncture of 1/2 right femoral bone length with a single photon bone density apparatus, and femoral anti-bending force was determined with a universal testing machine. Alkaline phosphatase were determined by dynamical method with an automatic biochemistry analyzer, urine calcium by EDTA titration method, urine creatinine by picric kinetic method, and urinary hydroxyproline by modified proline assay.Trabecular area was calculated.RESULTS: Forty rats were involved in the final analysis. ① Bone dry weight, bone ash weight and bone calcium content in the ovariectomized group were significantly lower than those in the other 3 groups, respectively (t =13.58-52.98, P ＜0.05). ② Femoral bone density and bone density of the whole body of rats in the ovariectomized group were significantly lower than those in the other 3 groups (t =3.31-5.61, P＜0.05), while anti-bending force was close between ovariectomized group and the other 3 groups (P＞0.05). ③ The ratio of urine calcium to urine creatinine was significantly lower in the ovariectomized+ibandronate group and ovariectomized +nilestriol group than in the ovariectomized group (t =4.04, 3.30, P＜0.05). No significant difference in the alkaline phosphatase and ratio of urinary hydroxyproline to urinary creatinine existed among the groups (P ＞ 0.05). ④Trabecular area of vertebrae in the ovariectomized group was significantly smaller than that in the other 3 groups (t =2.22,2.41,3.45,P ＜ 0.05), while the trabecular area of tibia in the ovariectomized group was only smaller than that in the ovariectomized +nilestriol group (t =2.45, P＜ 0.05).CONCLUSION: Osteoporosis apPears obviously in the SD rats 3 months after ovariectomy. Ibandronate has obviously inhibitory effects on the bone mass loss of rats with postmenopausal osteoposis, and it is equivalent to nilestriol in inhibitory effect.

Objective To explore the effects of daidzein (DA) on the expressions of estrogen receptors (ER) and peroxisome proliferator-activated recepor γ (PPARγ) in osteoblasts and the influence of estrogen on these effects.Methods A mouse osteoblastic cell line MC3T3-E1 cultured in α-MEM containing 2％ FBS was treated by 0.1 and 10 μmol/L DA.ER antagonist ICI182780 and PPARγ antagonist GW9662 in 0.1 μmol/L was added as required,and an equivalent amount of phosphate buffer solution (PBS) was used as control.For the study on estrogen effect,the cells were treated by DA in the serum-free medium with or without 10 nmol/L 17β-estradiol (E2).The expressions of ERa,ERβ and PPARγ were determined by real-time RT-PCR and Western blot analysis,respectively.Results DA inhibited ER,expression but stimulated PPARγ expression in the cells at the concentration of 0.1 and 10 μmol/L.The down-regulation of ERα by DA could be blocked by ICI182780,whereas the up-regulation of PPARγ could be repressed by GW9662 in transcription levels.Furthermore,the inhibitory effect of DA on ERβ expression was markedly enhanced,while its stimulatory effect on PPARγ expression was almost lost in serum-free medium with 10 nmol/L 17βestradiol as determined by real-time RT-PCR.Conclusions Besides its direct roles in ERs and PPARγ mediated gene transcriptions,DA could exert indirect effect on cellular pharmacological responses by altering ER and PPARγ expressions.The predominant influence on receptors expression probably involved in the time-related biphasic effects of DA on osteogenesis,which was supposedly influenced by estrogen level.

To investigate the roles of daidzein in the expressions of steroid receptor coactivator-1 (SRC-1) and nuclear receptor corepressor (NcoR) in MC3T3-E1 osteoblastic cells.

Objective To analyze the clinical and dosimetric risk factors for computed tomography (CT) grade of radiation-induced lung injury in lung cancer treated with three-dimensional conformal radiotherapy (3DCRT).Methods Eighty-nine lung cancer patients treated with 3DCRT were enrolled and CT scan images in more than 6 months were retrospectively analyzed.Clinical and dosimetric parameters were reviewed.Radiation-induced lung injuries were classified into 5 grades on CT images.Grade 3 or worse were considered clinically significant.Statistical software SPSS IS.0 was used to analyze the clinical and dosimetric risk factors that influenced the CT grade of radiation-induced lung injury.Results Eight of 89 patients (9.0%) developed grade 0 of radiation-induced lung injury,13 developed grade 1 (14.6%) ,24 developed grade 2 (27.0%) ,23 developed grade 3 (25.8%) and 21 developed grade 4 (23.6%).Univariable analysis showed that concurrent chemotherapy (CCT),GTV margin,involved ipsilateral lung mean lung dose(IMLD) ,the percent of involved ipsilateral lung receiving over IS,20,25 ,30,35 ,40 and 45 Gy (V_(15),V_(20) ,V_(25),V_(30) ,V_(35),V_(40) ,V_(45) were significantly associated with over grade 3 of radiation-induced lung injury .On multivariate logistic regression analysis,CCT,GTV margin and V_(20) of ipsilateral lung emerged as statistically significant risk factors of over grade 3 radiation-induced lung injuries CT images.Conclusions CCT,GTV margin and V_(20) of ipsilateral lung might be clinical and dosimetric risk factors associated with the severe CT grade of radiation-induced lung injury for lung cancer treated with 3DCRT.

Objective To analyze the clinical and dosimetric risk factors for acute radiation esophagitis (ARE) in non-small cell lung cancer (NSCLC) patients treated with three-dimensional conformal radiotherapy (3D-CRT),and to find significant risk factors for clinical therapy.Methods A total of 102 NSCLC patients treated with 3D-CRT were retrospectively analyzed.ARE was scored according to the Radiation Therapy Oncology Group (RTOG) criteria with grade 2 or worse.Patients were divided into non-concurrent chemoradiotherapy group and concurrent chemoradiotherapy group.The clinical and dosimetric factors associated with grade 2 or worse ARE were analyzed using univariate logistic regression,multivariate logistic analysis and receiver operating characteristic ( ROC ) curve.Results There were no grade 4 or5 ARE observed in the 102 patients.Nineteen developed grade 2,15 developed grade 3.In nonconcurrent chemoradiotherapy group,multivariate analysis showed that V55 was the only risk factor of grade 2/3 ARE.For ROC curve analysis,the cut-off point of V55 was 16.0 while the area under ROC curve was 0.870 ( 95 ％ CI:0.782 - 0.957,P ＜ 0.05 ).In concurrent chemoradiotherapy group,multivariate analysis showed that V35 and chemotherapy regimens during radiotherapy were risk factors of grade 2/3 ARE.The cut-off point of V35 was 23.75 while the area under ROC curve was 0.782 (95％ CI:0.636 -0.927,P ＜0.05).Vinorelbine and cisplatin regimen showed low incidence of ARE contrast with gemcitabine/docetaxel and cisplatin regimens (33.3％ and 66.7％ ).Conclusions V55 is the only statistically significant risk factor associated with grade 2 or worse ARE for patients who don't accepted concurrent chemotherapy.V35 and chemotherapy regimens during radiotherapy are statistically significant risk factors associated with grade 2 or worse ARE for patients who accept concurrent chemotherapy.Vinorelbine and cisplatin regimen during radiotherapy shows low incidence of ARE.

Objective To investigate the characteristic of lipoprotein(a)[Lp(a)]in different phases of chronic kidney disease (CKD ),to provide the basis for clinical prevention and treatment of CKD.Methods 200 patients with CKD in the Republic Hospital of Shifang were collected as study group,including 5 phases (every phase had 40 cases),and 100 healthy people were selected as control group.Measured the serum Lp(a)of both study and control group,analyzed the correlations between Lp(a)and different phase of CKD.All data were analyzed by SPSS version 17.0.The significant level was established at 0.05.Results CKD1 [(146.0 ±95.5)mg/L]and all CKD group [(231.5 ±133.2)mg/L]had higher level of serum Lp(a)than the control group [(115.5 ±70.2)mg/L] (Z=-2.800,P<0.05 and Z=-7.922,P<0.05).CKD3 had higher Lp(a)level than CKD2(Z=-2.069,P<0.05 ),while there were no significant differences between each of the other two groups.CKD4 -5 [(325 .0 ± 194.7)mg/L]also had higher Lp(a)level than CKD1 -3 [(182.0 ±110.5)mg/L](Z=-4.439,P<0.05). Conclusion Patients with CKD always have high level of serum Lp(a),which have been slowly increased since CKD1 ,meanwhile the level of Lp(a)may have a certain correlation with the stage of CKD development,since Lp(a) is an important promoting factor in the progress of CKD.

The important role of TDP-43 proteinopathy in Alzheimer's disease (AD) has been gradually revealed. High proportion of AD patients have TDP-43 proteinopathy on their postmortem diagnosis. Patients with TDP-43 proteinopathy show more sever hippocampal atrophy and cognitive dysfunction, suggesting that TDP-43 proteinopathy can serve as an important target in AD diagnosis and treatment. Evaluation of TDP-43 proteinopathy in vivo would hold great promise in AD diagnosis, drug development and treatment. In this review, we describe the pathological characteristics of TDP-43 proteinopathy in AD, and summarize the recent progress of TDP-43 proteinopathy in the diagnosis and treatment of AD.