1.Experimental research of repairing large segment of dogs bone defect with massive bioactive bone substitutes
Jianqiang XU ; Yunyu HU ; Chao ZHANG
Orthopedic Journal of China 2006;0(17):-
[Objective]To evaluate the effect of massive bioactive bone substitute in repairing large animals bone defect and to know its degrading rate.[Method]The massive Polylevolactic acid?collage calcium phosphate(PLLA?cTCP) carrieres by rapid forming technology was making,and then compounding rhBMP-2 and carrieres in a ratio of 3mg rhBMP-2 to one carrier was compounded to prepare the massive bioactive bone substitutes for dogs bone defect.Then the massive bone substitutes were implanted into 2.0cm dogss radius defects in the experiment group,and the massive carriers were implanted into in the control group.The repairing effect was evaluated by radiography,histology and biomechanics,and the degrading rate of the substitues was calculated in an image analysis apparatus.[Result]Radiographically,in the experiment group,the defects were connected by callus in all dogs in 12 weeks postoperatively;in 24 weeks,the callus rebuilt well.But in the control group,there was no callus formed in 24 weeks postoperatively,and the defects were not repaired.Histologically,in 12 weeks postoperatively,the outer layer of the callus in the experiment groups was lamellar bone and the center were trabecular bone,myeloid tissue and partial degrading carrier;in 24 weeks,the lamellar bone was more compact,trabecular bone decreased,myeloid tissue increased,and the carrier degraded more.In the control group,in 12 weeks postoperatively,the fibrous tissue wrapped and infiltrated into carrier,at the same time,part of the carrier degraded;in 24 weeks,the carrier was divided up by fibrous tissue and degraded more.The degrading rate of the carder in 12 weeks in the experiment group was 43.2%,in the control group was 35.7%,in 24 weeks 58.4% and 45.4%.Biomechanics,in 24 weeks after postoperation,the radius strength in the experiment group was superior to that in the normal bone.[Conclusion]The massive bioactive bone substitutes have satisfactory repairing effect on the radius bone defects of the large animal,but its degrading rate needs improving.
2.Autophagy effects on chondrocyte survival and cartilage damage
Xiezhuo ZHANG ; Chao XU ; Tuoheti YILIHAMU
Chinese Journal of Tissue Engineering Research 2015;19(20):3236-3241
BACKGROUND:Autophagy is the celular process of lysosomal pathway processing by endogenous substrates, which exists in the body cels and has been considered as type II programmed cel death. Autophagy may be a protective or balancing mechanism of normal chondrocytes. OBJECTIVE:To discuss the latest research progress in autophagy and cartilage damage aiming to better understanding the role of autophagy in cartilage damage and repair. METHODS:A computer-based search of CNKI, Wanfang database and PubMed database was performed for articles relevant to autophagy and cartilage damage published in recent 20 years with the key words of autophagy, cartilage, chondrocytes, beclin1, LC3 in Chinese and English. RESULTS AND CONCLUSION: Intra-articular chondrocytes can response to the changes in the microenvironment so as to adjust the extracelular matrix metabolism and maintain the biological function of articular cartilage. Hypoxic environment in which chondrocytes eixt is an important factor to causes autophagy. Autophagy is a normal balance or protection mechanism of chondrocytes. Studies on the correlation of autophagy with cartilage damage have made considerable progress in recent years, but stil in its infancy. Atg discovery at the molecular level deepens the understanding of autophagy, but the induction of cartilage autophagy pathway, signal transduction, and their effects on the survival of chondrocytes are not clear yet, which need further studies.
3.Meta-analysis of femoral shaft fractures treated with interlocking intramedullary nail and extramedullary plate
Xiezhuo ZHANG ; Chao XU ; Huiyong DING
Chinese Journal of Tissue Engineering Research 2016;20(17):24535-24544
BACKGROUND:With deep understanding of the concept of biological fixation, more and more physicians choose interlocking intramedulary nail in the repair of femoral shaft fracture. Compared with traditional extramedulary plate, the superiority of the interlocking intramedulary nail has not been reported at present. Randomized controled clinical study is less, and lacks of systematic evaluation.
OBJECTIVE:The results of meta-analysis were used to compare the therapeutic effects of interlocking intramedulary nail and steel plate for femoral shaft fractures.
METHODS: We retrieved the MEDLINE, Embase, PubMed, Cochrane library, CNKI, Wanfang database, and Vip database from 2000 to 2015 by computer to colect randomized controled study on interlocking intramedulary nail and extramedulary plate for treatment of femoral shaft fractures. We screened the literatures that met the inclusion criteria, were strict quality evaluation of the selection. Excelent and good rate, operation time, intraoperative blood loss, hospitalization time, recovery time of knee joint function reaching 135°, knee joint function recovery time of the second operation to remove the internal fixation for reaching 135°, postoperative drainage volume, fracture healing time, nonunion or delayed union, internal fixation loosening, postoperative infection, and osteomyelitis were considered as the evaluation index of meta-analysis. Meta-analysis was performed with RevMan 5.2 software from the Cochrane Colaboration.
RESULTS AND CONCLUSION:Finaly 10 Chinese articles were included, including 915 patients with femoral shaft fractures. The results of meta-analysis showed that compared with extramedulary plate, interlocking intramedulary nails for femoral shaft fractures could effectively reduce the amount of blood loss, postoperative drainage, shorten operation time, hospitalization time, fracture healing time, reduce the incidence of postoperative infection, and obtain recovery of knee joint function. These results suggest that interlocking intramedulary nail for treating femoral shaft fractures has certain advantages. The interlocking intramedulary nail can be firstly selected in the permit of patient’s economic conditions and hospital conditions.
4.Progress of immune environment steady after traumatic brain injury via regulating the polarization of macrophage/microglia by mesenchymal stem cells
Chao XU ; Xiaohong LI ; Sai ZHANG
Tianjin Medical Journal 2016;44(12):1514-1517,1518
Mesenchymal stem cells (MSCs), which are regarded as the promising option of cell replacement therapy, are able to regulate immune response after tissue damage caused by traumatic brain injury (TBI). Secondary neuroinflammation following the mechanical injury is the essential factor of neural cell necrosis and apoptosis, even after the intracranial pressure has returned to normal. Their immune environments caused by neuroinflammtary response determine the outcome and long-term behavior function of TBI in survivors directly. MSCs modulate macrophage/microglia, drive them to polarize into alternative M2-like cells through releasing soluble cytokines, such as prostaglandin E2 (PGE2), tumor necrosis factor-stimulated gene 6 protein (TSG-6), IL-1 and TGF-β, which limits the progression of inflammation and maintain micro-environment stable. Meanwhile, macrophage/microglia exerts significant effects in MSCs survival, proliferation, differentiation and activation. It provides a novel approach as a practical anti-inflammatory therapy in clinical treatment.
5.Evaluation of the stress distribution in tooth implant-supported fixed partial prostheses on different bone types under dynamic loads.
Yang ZHANG ; Chao WANG ; Xiaonan ZHANG ; Ling XU
West China Journal of Stomatology 2015;33(3):286-290
OBJECTIVEThis study aims to evaluate the influence of different bone types on the stress distribution in tooth implant-supported fixed partial prostheses by using finite element (FE) analysis.
METHODSFour FE models of mandibular arch containing one implant splinted to the mandibular second premolar were built according to bone types I, II, III, and IV. Dynamic loads of 250 N were applied to the buccal and lingual cusps of the prostheses in different directions to simulate the masticatory cycle. The maximum Von Mises stresses were calculated using the FE analysis software.
RESULTSThe maximum Von Mises stresses of the cortical bones were 89.229, 91.860, 125.840, and 158.420 MPa, increasing from type I to type IV, respectively. The maximum Von Mises stresses of the trabecular bone were 58.584, 43.645, 21.688, and 18.249 MPa, decreasing from type I to type IV, respectively. During the process of dynamic loading, the maximum Von Mises stresses of the cortical and trabecular bones followed the order buccal to tongue loading>tongue to buccal loading>vertical loading.
CONCLUSIONThe results showed that bone type significantly influenced the stress distribution in bones, and that for tooth implant-supported fixed partial prostheses, bone types I and II were a better choice than bone types III and IV. More caution should be exercised when restoring missing teeth using tooth implant-supported fixed partial prostheses in softer bone regions.
Bicuspid ; Bone and Bones ; chemistry ; Dental Implants ; Dental Prosthesis, Implant-Supported ; Dental Stress Analysis ; Denture, Partial, Fixed ; Finite Element Analysis ; Humans ; Stress, Mechanical
6.Mesenchymal stem cells modulate immune responses in a rat renal transplantation model
Chao QIN ; Wei ZHANG ; Zhijian HAN ; Dongliang XU ; Wei ZHANG
Chinese Journal of Organ Transplantation 2011;32(11):675-678
Objective To discuss the effect of mesenchymal stem cells (MSCs) in modulating immune responses in a rat renal transplantation model.Methods An in vivo trial of cytology was performed in one centre from March to December in 2008.Wistar rat donors and Lewis rat recipients in a renal transplantation model were randomly divided into 4 groups:MSCs (low dose,1 × 106 )therapy,MSCs (high dose,1 × 107) therapy,CsA monotherapy,and no therapy.Biochemistry methods were used to detect the levels of creatinine in serum.The survival time,renal grafting function and pathological changes of transplanted renal tissues were observed.Results Animal survival was significantly prolonged by MSCs (high dose) therapy and CsA monotherapy as compared with the no therapy group (both P<0.01).Animal survival in the MSCs (low dose) therapy group was prolonged as compared with no therapy group (P<0.01),but shortened as compared with MSCs (high dose) therapy group (P<0.05) and CsA monotherapy group (P<0.05).The MSCs (high dose) therapy and CsA therapy groups showed no special changes in histology,hut the control group showed acute rejection.Conclusion MSCs down-regulated immune responses,reduced production of some inflammatory mediators,preserved graft function in the initial stage after transplantation,and prolonged animal survival,and these effects were the same as those of CsA therapy with 1 × 107/day.
7.Epigenetic regulatory effects of the methylation of CpG island shore on the expression of lag3 gene in various human T cell lines
Shumin HAO ; Chao QIU ; Linxia ZHANG ; Xiaoyan ZHANG ; Jianqing XU
Chinese Journal of Microbiology and Immunology 2015;35(7):491-495
Objective To investigate the effects of DNA methylation on the expression of lympho-cyte activation gene 3 (lag3) in different human T cell lines.Methods A quantitative PCR and a flow cy-tometry analysis were performed to measure the expression of lag3 gene in various T cell lines at mRNA and protein levels.The distribution of CpG sites within the promoter and body of lag3 gene was detected to locate the potential regulatory region(s) (CpG island and CpG island shore).The levels of DNA methylation in each cell line were analyzed.The T cell lines were demethylated with 5-Aza-2′-deoxycytidine (5-Aza-2′-dc) for further investigation on the changes of lag3 gene expression and DNA methylation.Results Jurkat E6-1 cells showed the highest expression level of lag3 gene as compared with J.CaM1.6 and CEM cells.Hyperm-ethylated CpG islands were detected in cells of each cell line.The methylation levels of CpG island shore in J.CaM1.6 and CEM cells were higher than that in Jurkat E6-1 cells.Treatment of J.CaM1.6 and CEM cells with 5-Aza-2′-dc significantly promoted the expression of lag3 gene at mRNA and protein levels as well as the demethylation of CpG island shore.No significant differences with the expression of lag3 gene and the methylation of CpG island were observed in Jurkat E6-1 cells with or without 5-Aza-2′-dc stimulation.Con-clusion Methylation and demethylation of CpG island shore played important roles in regulating the tran-scription of lag3 gene.
8.Effects of up-regulated gene-4 on the proliferation of colonic cancer cells
Hao CUI ; Chao ZHANG ; Pan WANG ; Tao LIU ; Jianhua XU
Chinese Journal of Digestive Surgery 2012;11(3):290-293
Objective To study the effects of up-regulated gene-4 (URG-4) on colon cancer cellproliferation.MethodsColon cancer cell line with high expression of URG-4 was selected.The recombinant URG-4 siRNA retroviral vector was constructed and packaged by PT67 cell,then retroviral particles which can express URG-4 siRNA in mammal cell and its negative control were obtained.Expressions of URG-4 in MKN45,SW480,LoVo,HCT116,HT29 were detected by RT-PCR and Western blot,respectively.Recombinant virus (interference group),original virus (negative control group) and the same amount of PBS (blank group) were used to transfect LoVo cells respectively.Stably transfected cell lines were screened.The growth condition of cell lines in each group was assayed by MTT.All data were analyzed by the one-way analysis of variance and the t test.Results Sequencing results confirmed the successful construction of retroviral which expressed siRNA,the relative expression levels of URG-4 mRNA in MKN45,SW480,LoVo,HCT116,HT29 were 0.58 +0.02,0.63 ±0.03,0.81 ± 0.01,1.01 ± 0.02,0.91 ± 0.04 and the expression levels of URG-4 protein in the 5 cell lines were 0.73 ±0.02,0.85 ± 0.03,1.42 ± 0.01,0.80 ± 0.30,0.80 ± 0.04,respectively.High expression of URG-4 was observed in the LoVo cells.The expression of URG-4 mRNA in the LoVo cells in the interference group was 0.55 ±0.03,which was significantly lower than 1.15 ±0.02 of the negative control group and 1.15 ±0.01 of the blank group ( t =- 5.179,- 9.285,P < 0.05 ).The inhibition rate of URG-4 mRNA in the interference group was 52.6%.The expression of URG-4 protein in the interference group was 0.82 ± 0.05,which was significantly lower than 1.46 ± 0.07 of the negative control group and 1.54 ± 0.04 of the blank group (t =-4.239,-3.704,P<0.05).The inhibition rate of URG-4 protein in the interference group was 43.6%.The LoVo cells in each group grew exponentially.Compared with the negative control group,the cell growth of the interference group was inhibited during day 3 to day 6,which had statistical significant difference ( t =- 6.436,-6.045,-6.434,-4.285,P<0.05).ConclusionInterference of the expression of URG-4 can inhibit the growth of LoVo cells.
9.Short-time middle-load treadmill exercise affects the bone mineral density of hyperlipidemia male rats
Xiaohong WANG ; Chao XU ; Zhuo ZHANG ; Lianying GUO ; Bo ZHOU
Chinese Journal of Tissue Engineering Research 2013;(37):6555-6560
BACKGROUND:Some studies have shown that hyperlipidemia can lead to osteoporosis in rats, and exercise can increase the bone mineral density of rats. But the effect of short-time exercise on the bone mineral density of hyperlipdemia induced osteoporosis male rats is unclear yet.
OBJECTIVE:To investigate the effect of short-time middle-load treadmil exercise on the bone mineral density of hyperlipidemia male rats.
METHODS:Twenty-six male Sprague Dawley rats were randomly divided into three groups:control group (n=8), hyperlipidemia group (n=9) and exercise intervention group (n=9). The rats in the control group were fed with normal diet, and the rats in the other two groups were fed with high-fat diet and lasted for 4 weeks to establish the hyperlipidemia models. The rats in the exercise intervention group received treadmil exercise 5 days per week for 4 weeks according to the fol owing schedule:15 m/min for 15 minutes in the 1st week, 15 m/min for 20 minutes in the 2nd week, and then 20 m/min for 20 minutes in the last 2 weeks. Slope grade of the treadmil was adjusted at 0°. At the end of experiment, the rats were sacrificed, and the bone mineral density of the right femur, the morphological change of tibia, the level of plasma alkaline phosphates and calcium content were examined.
RESULTS AND CONCLUSION:Compared with the control group, the distal femur bone mineral density in hyperlipidemia group was significantly decreased (P<0.05);histological analysis of the proximal tibia showed thinning and loss of bony trabeculae arrangement, the gap was widened, and a large amount of fat cel s infiltration or integration into vacuoles in the marrow was observed, the plasma alkaline phosphates was significantly increased (P<0.01). Compared with the hyperlipidemia group, distal femur bone mineral density in the exercise intervention group was increased (P<0.05). After adjust body weight, the whole femur bone mineral density was significantly greater in exercise intervention group compared to hyperlipidemia group (P<0.05). The histological analysis of the proximal tibia showed that the spaces of bone trabeculae decreased and the structure of bone trabeculae compacted, the alkaline phosphates activities were increased (P<0.01). There were no significant differences in serum calcium and phosphates levels between groups. The results show that short-time middle-load treadmil exercise can increase the bone mineral density of hyperlipidemia male rats.
10.Biomechanical effects of osteoporosis vertebral augmentation on the adjacent intervertebral levels using a three-dimensional finite element analysis
Sheng LU ; Yong-Qing XU ; Mei-Chao ZHANG ;
Chinese Journal of Orthopaedic Trauma 2004;0(09):-
Objective To investigate effects of volume,distribution and leakage of bone cement in ver- tebroplasty on the adjacent intervertebral bodies using an experimentally calibrated and anatomically accurate fi- nite-element model of elderly L4-L5 vertebral bodies.Methods Computed tomography(CT)scanning was done,at 1 mm intervals,on L4-L5 vertebral bodies of the lumbar spine of an old man cadaver that had no abnormal findings on rnentgenograms.The L4-L5 motion segment data were obtained from the CT scans to establish in computer a three-dimensional finite element model of L4-L5 functional spinal unit(FSU)with the software Ansys 7.0.Compressive load after virtual vertebroplasty on the damaged model,unipedicular and bipedieolar injections and leakage of cement into the intervertebral space,and the resulting endplate and disc stresses of the adjacent vertebral bodies were analyzed in various spatial distributions of the filling material and different loading conditions. An anatomically accurate finite-element model of elderly L4-L5 vertebral bodies was developed.Results The FSU study suggested that changes in stress and strain at adjacent levels were minimal.Furthermore,endplale and disc stresses of the adjacent vertebral bodies were not influenced by bone cement filling volumes or distributions except under bending,whereas asymmetric distribution and leakage of bone cement to the disk increased the stress of adjacent endplates.Conclusion Since asymmetric distribution and significant leakage of cement into the intervertebral space can increase the stresses of endplates of adjacent vertebral bodies and may lead to a fracture, symmetric placement of cement in operation should be achieved and leakage of cement avoided.