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Objective To determine the effect of ostecytic TGF-β/Smad4 signaling on osteoblastic and osteoclastic differentiation in bone marrow stromal cells (BMSCs).Methods Mice with osteocytic TGF-β/Smad4 conditional knock down (Smad4ot CKD) were generated as previously by crossing DMP1-8kb-Cre mice with Smad4lox(ex8)/lox(ex8) mice.The osteocytes were isolated from tibial and femoral diaphysis and co-cultured with wild-type BMSCs.ALP staining, Alizarin red staining and TRAP staining were performed to show osteoblastic and osteoclastic differentiation.Then, their marker genes were detected by qPCR and proteins measured by Western blot.ResultsThe expression of Runx2 and Osterix were reduced in smad4 CKDot co-cultured with BMSCs compared with controls(P<0.01).Similarly, the specific markers of osteoblastic differentiation were decreased (P<0.01).Additionally, the expression of RANKL was not significantly changed in with BMSCs.However, OPG was highly expressed incontrol group compared with smad4 CKD in co-cultured group (P<0.05).Thus, the radio of RANKL/OPG was significantly reduced (P<0.05).Furthermore, the expression of RANK was inhibited.Conclusions The terminally-differentiated osteocytes are the cells regulating bone metabolism, while down-regulation of osteocytic-TGF-β/Smad4 inhibits BMSC osteoblastic and osteoclastic differentiation.
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Objective To investigate the clinical efficacy of domestic porous tantalum rod in treatment of early avascular necrosis of femoral head (ANFH).Methods A prospective study was made on 18 cases (19 hips) diagnosed as early ANFH treated by domestic porous tantalum rod from July 2014 to December 2015.There were 14 males and four females, with a mean age of 44.2 years (range, 30-62 years).According to the modified Ficat staging, four cases were identified as stage Ⅱa and 14 stageⅡb.Efficacy of the treatment was evaluated by Harris score, Womac score, radiological images of the hip, complications and bone growth.Results All cases were followed up for 8-24 months (mean, 16 months).No complications such as infection, wound healing problems, immunological rejection, tantalum rod breakage, loosening or displacement were observed at last follow-up.Harris score was (82.7±9.0)points, (84.5±10.8)points and (87.2±10.0)points at postoperative 3, 6 and 12 months respectively, significantly higher than that pre-operation [(75.5±11.9)points] (P<0.05).Harris score was rated excellent in 10 cases, good in three, fair in five and poor in one at the last follow-up, with the excellent and good rate of 68%.Womac score was (17.4±9.4)points, (12.4±7.3)points, and (11.1±8.4)points at postoperative 3, 6 and 12 months respectively, significantly lower than that pre-operation [(28.3±13.1)points] (P<0.05).Seventeen cases (18 hips) showed no obvious deterioration in femoral head necrosis, with femoral head survival rate of 95%.One case underwent total hip arthroplasty after operation because of progressive hip pain and collapsed femoral head.Bone ingrowth was detected in the porous tantalum biomaterial after operation.Conclusion Domestic porous tantalum rod can effectively promote bone ingrowth, relieve pain, prevent the collapse of the femoral head, delay total hip arthroplasty time and finally improve hip function in treatment of early avascular necrosis of femoral head.
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Objective To observe the expression of immune substances secreted by peripheral bloodγδT cells after stimulated by early secreted antigenic target-6(ESAT-6),and explore its mechanism of signaling pathway.Methods Peripheral blood mononucle-ar cells(PBMC)were collected from health human blood with the ficoll density gradient centrifugation method,and theγδT cells were separated from the PBMC with flow cytometry;the inhibitor of TLR-4 signaling pathway(E5564)was used to cocultured withγδT cells to inhibit the function of TLR-4,and the change of TLR-4 was analyzed by the methods of PCR and Western blot.ESAT-6 were used to stimulate theγδT cells,and the control group without any stimulating factor was established,then the expression levels of IL-17,TNF-α,IFN-γwere determined by ELISA method after 0、1、3、6、9 and 12 days.Results The results of PCR and Western blot showed that ESAT-6 could increase the expression of TLR-4(P<0.01);The results of ELISA showed that ESAT-6 could enhance the expression of IL-17,TNF-αand IFN-γ(P<0.01),and the inhibitor of TLR-4(E5564)could decrease the expres-sion of IL-17,INF-α,IFN-γ(P<0.01).Conclusion ESAT-6 can induceγδT cells to produce more IL-17,TNF-α,IFN-γ,and the mechanism of which maybe concerned with TLR-4 signaling pathway.
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BACKGROUND: Nervousness, anxiety and depression are important inducing factors of migraine, while nervousness, anxiety and depression are closely correlated with the unreasonable belief and incorrect strategy. Medicine therapy is the principal method in the treatment of migraine at present, but it cannot change the unreasonable belief of the patients and thereby to reducethe occurrence of the inducing factors of headache.OBJECTIVE: To observe the near term and long term therapeutic effects of medicine therapy and rational emotional behavior therapy(REBT) to provide a safer and more effective intervention for the patients with migraine and thereby to improve their long term quality of life(QOL).DESIGN: An observatory comparative study based on patients with migraine as subjects and healthy population as controls.SETTING: A psychological consultation clinic of a municipal hospital(has been canceled now).PARTICIPANTS: Totally 86 cases of migraine including 34 males and 52females aged between 16 and 48 years old(means of 35 years old) with a course of disease between 2 and 11 years were selected from the Psychological Consultation Clinic of the 289 Hospital between March 1999 and October 2001. All 86 cases were randomly divided into REBT group and medicine group with 43 cases each. There was no significant difference of age, gender,course of the disease, situation of the disease, and education background between two groups. Another 30 healthy individuals including 12 males and 18 females with a mean age of 36 years old were selected in control group.METHODS: REBT was applied for patients in REBT group. Patients of medicine group received 50-100 mg/day of Amitriptyline and 60 mg/day of nimodipine through oral administration. Patients received 12 weeks of therapy followed by 24 weeks of observation.MAIN OUTCOME MEASURES: Therapeutic scale score on migraine (TSSM), before and after migraine-correlated potential(P300) and symptoms checklist 90 (SCL-90) scores were compared.RESULTS: SCL-90 total points of two groups of patients were significantly higher than that of control group( P ＜ 0.05); after 12 weeks of therapy,TSSM, SCL-90 total points and points of major factors of two groups of patients were significantly lower compared with the situations before therapy( P ＜ 0.05), but there was no significant difference between two therapy groups; on the 12th week after therapy, SCL-90 total points, points for major factors and TSSM, and P300 latency of REBT group were almost as the same as that after 12 weeks of therapy and the wave amplitude of P300 significantly elevated; owever, the differences in SCL-90 total points, points of major factors, and the TSSM in medicine group were significant compared with that after 12 weeks of therapy( P ＜ 0.05) . There was significant difference at the same period between two therapy groups ( P ＜ 0.05).CONCLUSION: REBT can reduce the attacks of migraine, decrease TSSM,and has similar therapeutic effects to medicine group. Simultaneously, it can ameliorate the cognitive disorder, change the unreasonable belief of the patients, and improve the strategy to cope with the disease; hence its long term therapeutic effect is better than medicine therapy.
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This study sought to synthesize a triple helix-forming phosphorothioate oligodeoxynucleotides (TFO-ps) and assess its effects on coagulation activity of the tissue factor(TF) and TF gene expression in endothelial cells. Experiment antiparallel oligodeoxynucleotides T21GTa sequence was designed and synthesized by phosphoramidite method and decorated with all-PS linkage. The affinity of TFO and TFO-ps was determined by electrophoretic mobility shift assays(EMSA). Cellular uptake of [32]P-labeled TFO-ps and the effect of TFO-ps on TF gene expression and coagulation activity of TF were measured in endothelial cell strain ECV304. The results showed that TFO-ps (T21GTa-ps) formed a triplex binding in antiparallel orientation to the puring-rich target strand-SSRE, with Kd value of 3.6 x 10(-10) M. The uptake rate of TFO-ps (T21GTa-ps) in ECV304 was about 11.65%. This compound mainly localized within the nucleus sediment(77.25%), significantly reduced the average OD of the mRNA expression and protein synthesis of TF gene, and obviously decreased the coagulation activity of TF. In conclusion, TFO-ps (T21GTa-ps) shows obvious anti-coagulation activity and its mechanism involves the inhibition of TF gene expression.
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Humans , Blood Coagulation , Cells, Cultured , Endothelium , Cell Biology , Gene Expression , Oligodeoxyribonucleotides , Pharmacology , RNA, Messenger , Thromboplastin , Genetics , PhysiologyABSTRACT
Objective To investigate the characteristics of memory impairment in patients with ischemic cerebrovascular diseases(ICVD)for further understanding in the cognitive impairment at early stage.Methods Forty-six ICVD patients aged 49 to 80 years old and forty-six matched volunteers,all from the same hospital during Sep 2005 to Feb 2006,were enrolled.Mini-mental state examination(MMSE),clinical memory scale(CMS),Fuld object-memory evaluation(FOM)and rapid verbal retrieve(RVR)were used to evaluate the cognitive and memory function.Results The ICVD patients had lower scores in every memory function than the controls(P
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Objective To investigate the roles of c-reactive protein (CRP) in the onset of dysthymia and its effects on the therapeutic efficacy. Methods Ninety six patients with dysthymia (male:37, female: 59) were examined using Hamilton depression scale (HAMD) to determine their status of depression at 2 months before and after treatment with fluoxetine. Another 50 normal subjects were employed as the controls. CRP levels were measured by scatter turbidimetry by TurboxR special protein analysis system (Finland) in all subjects. Results All depression scores of normal subjects according to HAMD depression scale were under 17 and their serum CRP concentrations were at a basic level. The prevalence rate of increase of serum c-reactive protein in dysthymia was 43.8%(42/96). The average serum CRP level in patients with dysthymia was significantly higher than that in normal subjects (P0.05). Conclusion Serum CRP concentration maybe an important evoking factor of dysthymia. It may not increase the severity of depression but may impede the early improvement of symptoms.
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Objective: To observe the effect of Deanxit and Nimodipine on the headache of anxiety and depression neurosis. Methods:Fifty anxiety and depressive neurosis patients with headache were randomly divide into groups A and B. Group A: Daenxit and nimodipine therapy,group B: Deanxit therapy. All the patients were examined in TCD, Hamilton Anxiety Scale, Hamilton Depression Scale (HAMH、HAMD)and the chief symptom changes before and after therapy. Results: Eight weeks after therapy, the cerebral blood fluid in group A was improved,but it was insignificant in group B. The symptoms of anxiety,depression and headache in group A were much better improved than that of group B. Conclusion: Deaxit had a better anti-anxiety and antidepression function. Nimodipine could improve markedly headache less for anxiety and depression. It was more effect that synthetic therapy than single anti-anxiety and antidepression.