Developmental toxicity and programming alterations of multiple organs in offspring induced by medication during pregnancy

Medication during pregnancy is widespread, but there are few reports on its fetal safety. Recent studies suggest that medication during pregnancy can affect fetal morphological and functional development through multiple pathways, multiple organs, and multiple targets. Its mechanisms involve direct ways such as oxidative stress, epigenetic modification, and metabolic activation, and it may also be indirectly caused by placental dysfunction. Further studies have found that medication during pregnancy may also indirectly lead to multi-organ developmental programming, functional homeostasis changes, and susceptibility to related diseases in offspring by inducing fetal intrauterine exposure to too high or too low levels of maternal-derived glucocorticoids. The organ developmental toxicity and programming alterations caused by medication during pregnancy may also have gender differences and multi-generational genetic effects mediated by abnormal epigenetic modification. Combined with the latest research results of our laboratory, this paper reviews the latest research progress on the developmental toxicity and functional programming alterations of multiple organs in offspring induced by medication during pregnancy, which can provide a theoretical and experimental basis for rational medication during pregnancy and effective prevention and treatment of drug-related multiple fetal-originated diseases.

The promotion of bone formation at the tendon-bone interface after ACL reconstruction with De-BMSCs transplantation and its mechanism / 中华骨科杂志

Objective:This study aimed to investigate the effect of differentiation osteogenic bone marrow mesenchymal stem cells (De-BMSCs) transplantation on the promotion of bone formation at the tendon-bone interface after anterior cruciate ligament reconstruction (ACLR), and further explored the molecular mechanism of the enhanced osteogenic effect of De-BMSCs.Methods:BMSCs from femur and tibia of New Zealand White rabbit were subjected to osteogenic induction and then cultured in no osteogenic factor medium; the obtained cell population was termed De-BMSCs. De-BMSCs were induced into osteo-, chondro-and adipo-differentiation in vitro to examine the characteristics of primitive stem cells. ACLR model with a semitendinosus tendon were performed in 48 adult rabbits, three groups were established: control group with alginate gel injectionat the tendon-bone interface, BMSCs group with the injection of alginate gel containing BMSCs, De-BMSCs group with the injection of alginate gel containing De-BMSCs. At 4 and 12 weeks after surgery, rabbits in each group were sacrificed to evaluate tendon-bone healing by histologic staining, micro-CT examination, and biomechanical test. During osteogenic differentiation of De-BMSCs, si-RNA of nuclear factor of activated T cells 2 (NFATc2) si-RNA of nuclear factor of activated T cells 1 (NFATc1) were used to verify the molecular mechanism of enhanced osteogenic effect of De-BMSCs.Results:De-BMSCs exhibited some properties similar to BMSCs including multiple differentiation potential and cell surface marker. At 4 weeks after surgery, the BV/TV value of the De-BMSCs group 0.36±0.01 was significantly higher than that of the control group 0.24±0.03 and BMSCs group 0.30±0.02 (all P<0.05), and the maximum load 40.34±1.19 N and stiffness 20.67±2.14 N/mm were significantly higher than those in the control group 14.88±2.74N, 8.67±2.19 N/mm and the BMSCs group 26.31±1.76 N, 13.81±2.14 N/mm (all P<0.05). At 12 weeks after surgery, the BV/TV value of the De-BMSCs transplantation group 0.47±0.02 was significantly higher than that of the control group 0.30±0.02 and the BMSCs group 0.35±0.03 (all P<0.05), and the maximum load 64.46±6.69 N and stiffness 25.18±3.11 N/mm were significantly higher than those in the control group 41.01±6.12 N, 11.59±2.54 N/mm and the BMSCs group 48.21±4.12 N, 15.89±2.94 N/mm (all P<0.05). During the osteogenic differentiation of De-BMSCs, the expressions of Nanog and NFATc1 were synergistically increased which promoted interaction of NFATc1 and Osterix ( P< 0.05), resulting in the increased expression of osteoblast marker genessuch as COL1A, OCN, OPN (all P< 0.05). Conclusion:De-BMSCs transplantation could promote bone formation at the tendon-bone interface after ACLR,Nanog/NFATc1/Osterix signaling pathway mediated the enhancement of the osteogenic differentiation effect of De-BMSCs.

Effect of cholesterol on human meniscal fibrochondrocytes / 中华创伤骨科杂志

Objective:To explore the effect of cholesterol on the expression of genes for matrix synthesis and degradation of human meniscal fibrochondrocytes and its mechanism.Methods:Meniscal tissue was taken from patients undergoing arthroscopic surgery to extract fibrochondrocytes. The cells were divided into a control group in which the normal cells were not processed, a positive control group in which interleukin-1 β was used to create a degeneration model, and 2 treatment groups which were subjected to treatment with 15 and 30 μg/mL cholesterol respectively. Safranin O staining, β-galactosidase staining and enzymic kits were used to detect the morphology and total cholesterol (TCH) content of meniscal fibrochondrocytes in the 4 groups. Immunofluorescence and western blot were used to detect the protein expression of type Ⅰcollagen precursor α1 (COL1A1) and type Ⅱ collagen precursor α1 (COL2A1). RT-qPCR was used to detect the mRNA expression of COL1A1, COL2A1, matrix metalloproteinase (MMP) 3, MMP9, MMP13, and genes related to cholesterol efflux pathways [like liver X receptor α (LXR α), ATP binding cassette transporter A1 (ABCA1) and ABCG1]. Results:There was no significant difference between the control and the positive control groups in the TCH content in human meniscal fibrochondrocytes ( P>0.05). The treatments with 15 and 30 μg/mL cholesterol resulted in significantly increased TCH contents in human meniscal fibrochondrocytes in the treatment groups ( P<0.05). Compared with the control group, the mRNA expression of LXR α, ABCA1 and ABCG1 was significantly decreased in the treatment groups ( P<0.05), and the meniscal fibrochondrocytes in the positive group and the treatment groups presented with a lower density, chaotic distribution and obvious signs of degradation. Compared with the control groups, the mRNA expression of matrix synthesis genes (COL1A1 and COL2A1) in the meniscal fibrochondrocytes was significantly inhibited while the mRNA expression of matrix degradation metalloenzymes (MMP3, MMP9 and MMP13) was significantly promoted ( P<0.05). Conclusion:Cholesterol may inhibit the cholesterol efflux pathways of meniscal fibrochondrocytes, and thus cause accumulation of cholesterol in the meniscal fibrochondrocytes, eventually leading to degeneration of meniscus.

Therapeutic effects of early reconstruction of medial patellofemoral ligamenton acute traumatic patellar dislocation of knee / 临床外科杂志

Objective To evaluate the therapeutic effects of early reconstruction of medial patellofemoral ligament (MPFL) in acute traumatic patellar dislocation of knee joint.Methods 15 acute traumatic patellar dislocation of knee joint patient underwent early MPFL reconstruction, and were regular follow-up after operation.At the final follow-up, evaluated the stability of patellar and compared the Lysholm score, Kujala score and Tegner score between pre-injury and last follow.Results The average follow up was 18.6 months.All the patient had no recurrent patellar dislocation, and showed negative apprehension test.The preinjury Lysholm score, Kujala score and Tegner score were 90.6±13.1, 92.3±12.4 and 5.9±1.3, respectively;the postoperative Lysholm score, Kujala score and Tegner score were 91.2±12.5, 95.1±13.2 and 6.2±1.6.There were no significant difference between before injury and postoperation on Lysholm score, Kujala score and Tegner score at last follow-up (P＞0.05).Conclusion Early MPFL reconstruction for acute traumatic patellar dislocation can restore the stability and function of patellar.

Projection marking to optimize antegrade femoral intramedullary nailing / 中华创伤骨科杂志

Objective To evaluate the projection marking which was designed to improve the surgical efficiency of antegrade femoral intramedullary nailing for femoral intertrochanteric and shaft fractures.Methods A total of 198 patients (158 femoral intertrochanteric fractures and 40 femoral shaft fractures) were analyzed retrospectively who had been treated at Department of Orthopedics,The First Affiliated Hospital to Wenzhou University from January 2012 to January 2016.They were 61 males and 137 females,aged from 13 to 95 years (mean,65.4 ± 14.6).By AO classification,there were 55 cases of type 31-A1,103 cases of type 31-A2,21 cases of type 32-A2 and 19 cases of type 32-A3.The intertrochanteric fractures which had been treated from January 2012 to May 2013 with no projection marking were assigned into group A1 (n =61) while the shaft fractures which had been treated in the same period with no projection marking into group B1 (n =12);the intertrochanteric fractures which had been treated from May 2013 to January 2016 with projection marking were assigned into group A2 (n =97) while the shaft fractures which had been treated in the same period with projection marking into group B2 (n =28).Comparisons were made between groups A1 and A2,and between groups B1 and B2 in terms of total operative time,total number of fluoroscopy,complications,Harris hip score (HHS),and pain and symptoms scores in Knee Injury and Osteoarthritis Outcome Score (KOOS) 3 months after operation.Results The 198 patients were followed up for 3 to 18 months (average,7.0 months).The total operative time (56.5 ±6.6 min) and the total number of fluoroscopy (26.6 ±6.2 times) in group A2 were significantly less than those in group A1 (59.2 ±9.2 min and 31.4 ±9.9 times) (P ＜ 0.05).The total operative time (84.6 ± 16.1 min) in group B2 was significantly less than that in group B1 (97.8 ± 17.9 min) (P ＜0.05) but the total number of fluoroscopy (49.4 ± 12.7 times) in group B2 was insignificantly less than that in group B1 (50.6 ± 10.1 times) (P ＞ 0.05).Conclusion The self-designed designed method of projection marking can reduce operative time and number of intraoperative fluoroscopy in the antegrade femoral intramedullary nailing for femoral intertrochanteric and shaft fractures.

Clinical application of uncemented distal stem fixation for revising femoral prosthesis of hip arthroplasty in elderly patients / 中华老年医学杂志

Objective To evaluate the effectiveness of uncemented distal stem fixation for elderly patients needing revision of femoral prosthesis of hip arthroplasty.Methods From July 2005 to January 2013,22 patients(12 males and 10 females)aged from 70 to 85 years(average:76 years old) with aseptic loosening of the femoral stem undergone revision via uncemented distal stem fixation were enrolled into this study.Of all patients,10 had revision on the right side and 12 on the left side;11 patients received artificial replacement of the femoral head;9 had total hip replacements;2 had femoral fractures.According to the Paprosky classification system,2 cases were type Ⅰ,12 were type Ⅱ,6 were type [Ⅲ A,and 2 were type Ⅲ B.Femoral stems for revision included MP(Link)and Solution(Depuy).The Harris score,clinical and radiological results were retrospectively analyzed.Results All patients were followed up for 48 to 78 months(mean:61 months).The average Harris score increased from 38 (25-46) to 87 (76-94).All prostheses were initially stable,and no infection,dislocation or complication like deep venous thrombosis was observed after revision.All patients were able to walk without assistance;two of them had minor claudication;radiographs after surgery showed well-positioned implants with increased bone density and thickness around the prosthesis and without loosening or subsidence.Conclusions Reliable axial and anti-rotational stability can be achieved by using uncemented distal stem fixation,with good short-and medium-term clinical results for revision in elderly patients with less severe bone defects than those in Paprosky Ⅳ.

Study of gender difference on perioperative hidden blood loss of intertrochanteric fracture / 中华骨科杂志

Objective To investigate the hidden blood loss of intertrochanteric fractures in different gender. Methods Data of 108 patients with intertrochanteric fractures who were admitted to the department of orthopaedics from January 2012 to De?cember 2015 were retrospectively analyzed. For all patients who were composed of 42 males and 66 females and whose ages ranged from 32 to 95 years old, the average age was 75.4±10.8 years old. With the equation of Gross, the amount of perioperative hidden blood loss (PHBL) was calculated as well as the fraction of PHBL. The lineal regression model was utilized to analyze the correlations between PHBL and those factors including age, time interval between injury and surgery, injured side, Evans classifi?cation of intertrochanteric fractures, patients' ASA grade, and type of anesthesia. The difference of hemoglobin (Hb), hematocrit (Hct), total blood volume, the amount of PHBL, and the percentage of PHBL were respectively compared between male group and female group. Results PHBL had no correlation of lineal regression with age, time interval between injury and surgery, injured side, Evans classification of intertrochanteric fractures, patients' ASA grade, or the type of anesthesia. The share of PHBL did not have correlation of lineal regression with age, time interval between injury and surgery, injured side, Evans classification of inter?trochanteric fractures, patients' ASA grade, or the type of anesthesia as well. Lineal regressive correlation only existed between gender factor and the PHBL fraction of total blood volume, and there was no regressive correlation between gender factor and the amount of PHBL. In the male group, the mean amount of preoperative Hb was 121.8±16.6 g/L and preoperative Hct was averagely 36.7%±5.0%;in the female group, the amount of preoperative Hb was 99.5±13.1 g/L on average and the mean amount of Hct was preoperatively 30.6%± 3.7%. Postoperatively, the mean amount of preoperative Hb was 103.4 ± 19.3 g/L and Hct was averagely 29.8%±4.2%;in the female group, the amount of postoperative Hb was 79.0±10.4 g/L on average and the mean amount of Hct was postoperatively 23.9%± 2.6%. Significant difference of perioperative Hb and Hct was found between two groups. The total blood volume was averagely 4 500.6±191.5 ml in the male group and 3 607.0±235.7 ml in the females group. There was statistical differ?ence between two groups. For male group, the amount of PHBL was 647.9±174.1 ml on average and accounted for 14.4%±4.0%of total blood volume. For the female group, the mean amount of PHBL was 694.8±216.5 ml and making up 19.3%±6.1%of the total blood volume. As for the amount of PHBL, no significant difference was observed between male group and female group, but there was statistical difference of the share of PHBL accounting for total blood volume between two groups. Conclusion Female pa?tients' PHBL fraction of total blood volume is greater than male patients', therefore females' PHBL conditions need to be paid more attention to and ought to be corrected in time.

Quality of Care for People with Disabilities and Related Factors in Hubei, China / 中国康复理论与实践

Objective To investigate the current situation of quality of care for people with disabilities and the related factors. Methods In November, 2015, 399 disabled persons from five special service institutions in Hubei, China were conveniently sampled, and investigated with the Chinese version of Quality of Care and Support (QOCS) for people with disability scale and demographic questionnaire. Results The total score of QOCS was (38.11±6.24), and the proportion of total score in the dimensions of caring provision, caring environment and caring information were more than 70%. The score of QOCS was various with the age, domicile, employment, medical insurance, monthly household expenditure and expenditure for food of the people with disabilities, and the age (β=0.06, P<0.01) and medical insurance (β=-0.850, P<0.001) were the independent factors related with the score of QOCS. Conclusion People with disabilities self-reportedly satis-fied in the quality of care in Hubei, and it can be improved from the increase of medical insurance level.

Current therapeutic progression of Rifampicin in prosthetic joint infection / 中华骨科杂志

Prosthetic joint infection (PJI) is a devastating complication that can occur after any arthroplasty procedure and is associated with significant morbidity and substantial healthcare costs.Recently,the use of Rifampicin in PJI subjects has become a hot research direction in the field of orthopaedics,its efficacy is definite and encouraging.But till date,to the best of our knowledge,we still have no associated reports about the application of Rifampicin on PJI.Therefore,articles concerned with the administration of Rifampicin in PJI subjects published till date were retrieved from PubMed,Cochrane Library,Embase,China National Knowledge Infrastructure,Wanfang and Weipu databases.The articles,which met the inclusion and exclusion criteria,were summarized into the following categories:1) The development and the application status of Rifampicin on PJI;2) The therapeutic mechanism of Rifampicin on PJI;3) The usage of Rifampicin in the postoperative antimicrobial therapy.By reviewing the associated articles,we found out that PJI is difficult to treat,because the causative bacteria forms and exists in a biofilm that is adherent to the prosthetic surface.The formation and maturation of the bacterial biofilm is a time dependent process.The longer the biofilm exists,the troublesome it gets to eradicate.Rifampicin not only has an excellent anti-staphylococcal activity,but also has a very good oral bioavailability and good bone penetration.The application of Rifampicin may significantly improve the surgical success rate especially after debridement and retention in PJI subjects.However,the optimal course,dosage and route of administration still need further exploration.

Expression of interleukin-17 and its biological significance in serum and synovial fluid of knee oste-oarthritis / 临床外科杂志

Objective To determine the interleukin(IL)-17 concentrations in serum and synovi-al fluid from patients with knee osteoarthritis(OA),and evaluate their correlation with disease severity. Methods Serum and synovial fluid were collected from 100 patients with primary knee OA;age-and sex-matched 50 healthy subjects provided serum samples as controls.OA severity and grade were assessed u-sing the Lequesne index and Kellgren and Lawrence(K-L)grading system,respectively.The expression of IL-17 was quantified by enzyme-linked immunosorbent assay.Results Serum IL-17 concentrations were significantly higher in patients than in controls(P <0.05).In the patient group,patients with K-L grade 3 and 4 had higher synovial IL-17 levels than those with K-L grade 2(P <0.05).At the same time,com-pared with K-L grade 3,there was a higher IL-17 level in K-L grade 4 patients(P <0.05).Synovial fluid IL-17 concentration was positively correlated with Lequesne index(r =0.6232,P <0.05).There was no correlation between serum IL-17 concentrations and Lequesne index,however.Conclusion The expres-sion of IL-17 was significantly increased in serum and synovial fluid of knee from patients with knee OA. There was a positive correlation between synovial fluid IL-17 concentrations and OA severity.It suggests that the imbalance of IL-17 expression plays a certain role in the pathogenesis of OA.

Current status of diagnosis and treatment for medial collateral ligament injury of the knee / 临床外科杂志

Medial collateral ligament injury is the most common injury of the knee ligament. Most patients with conservative treatment can achieve preinjury activity level. Nonetheless,it's necessary to eval-uate the severity of the injury and judge the best time and details for surgery as serious injury of the medial collateral ligament will cause chronic knee stability and accelerate its degeneration. This paper summarizes the current status of diagnosis and treatment for medial collateral ligament injury of the knee,aiming to pro-vide guidance for dealing with this lesion.

Bone marrow mesenchymal stem cells transfected with recombinant adenovirus vectors carrying basic fibroblast growth factor in co-culture with ligament fibroblasts / 中国组织工程研究

BACKGROUND:Basic fibroblast growth factor (bFGF) plays an important role in the ligament tissue healing process, and bone marrow mesenchymal stem cel s transfected with growth factors can be used as seed cel s in ligament tissue engineering. OBJECTIVE:To observe biological effect of bone marrow mesenchymal stem cel s transfected with recombinant adenovirus vectors carrying bFGF in three-dimensional co-culture with ligament fibroblasts. METHODS:Passage 3 bone marrow mesenchymal stem cel s were divided into three groups:control group, Ad-EGFP group and Ad-bFGF group. Under a phase contrast microscope, the changes in cel morphology were observed and the rate of transfection was analyzed by flow cytometry. Proliferation of bone marrow mesenchymal stem cel s and ligament fibroblasts was analyzed by MTS, the expression of bFGF protein in bone marrow mesenchymal stem cel s was determined by ELISA. Scleraxis, col agen type I, col agen type III, decorin and cartilage oligomeric matrix protein levels were detected in BMSCs and ligament fibroblasts using real-time fluorescent quantitative PCR. RESULTS AND CONCLUSION:Recombinant adenovirus-mediated bFGF gene could transfect bone marrow mesenchymal stem cel s efficiently. After co-culture for 3, 6 days, compared with the control group and Ad-EGFP group, in the Ad-bFGF group, the proliferation ability of bone marrow mesenchymal stem cel s and ligament fibroblasts was enhanced (P<0.01), the expression of bFGF protein in supernatant was obviously higher (P<0.01), the col agen type I, col agen type III, decorin and cartilage oligomeric matrix protein mRNA expression decreased in the ligament fibroblasts (P<0.01), but the mRNA expression of Scleraxis, col agen type I, col agen type III in bone marrow mesenchymal stem cel s increased (P<0.01). The results suggest that the co-culture of Ad-bFGF-transfected bone marrow mesenchymal stem cel s with ligament fibroblasts promotes the proliferation of ligament fibroblasts while decreases the col agen synthesis at the same time, and stimulates the proliferation and differentiation of bone marrow mesenchymal stem cel s into ligament fibrolasts.

Effects of sintered bone modified with surface mineralization/P24 peptide composite biomaterial on the adhesion, proliferation and osteodifferentiation of MC3T3-E1 cells / 生物医学工程学杂志

In the present research, the effects of sintered bone modified with surface mineralization/P24 peptide composite biomaterials on the adhesion, proliferation and osteodifferentiation of MC3T3-E1 cells were investigated. The experiments were divided into three groups due to biomaterials used: Group A (composite materials of sintered bone modified with surface mineralization and P24, a peptide of bone morphogenetic protein-2); Group B (sintered bone modified with surface mineralization) and Group C (sintered bone only). The three groups were observed by scanning electron microscopy (SEM) before the experiments, respectively. Then MC3T3-E1 cells were cultured on the surfaces of the three kinds of material, respectively. The cell adhesion rate was assessed by precipitation method. The proliferative ability of MC3T3-E1 cells were measured with MTT assay. And the ALP staining and measurement of alkaline phosphatase (ALP) activity were performed to assess the differentiation of cells into osteoblasts. The SEM results showed that the materials in the three groups retained the natural pore structure and the pore sizes were in the range between 200-850 μm. The adhesive ratio measurements and MTT assay suggested that adhesion and proliferation of MC3T3-E1 cells in Group A were much higher than those in Group B and Group C (P < 0.05). The ALP staining and ALP activity of MC3T3-E1 cells in Group A were significantly higher than those in Group B and Group C (P < 0.05). The sintered bone modified with surface mineralization/P24 composite material was confirmed to improve the adhesion rate and proliferation and osteodifferentiation of MC3T3-E1 cells, and maintained their morphology.

Transgenerational effects of prenatal ethanol ingestion-induced susceptibility to metabolic syndrome and the underlying mechanism in F2 rats / 中国药理学与毒理学杂志

OBJECTIVE To investigate the transgenerational effects of a hypothala mic-pituitary-ad-renal (HPA)axis -associated neuroendocrine metabolic progra mming alteration fro m F1 to adult second generation (F2)with prenatal ethanol ingestion.METHODS Pregnant Wistar rats were ad ministered with ethanol (4 mg·kg -1·d -1 )fro m gestational day 1 1 until delivery.F1 rats were fed a high-fat diet fro m postnatal week 4 (PW4)and were cross-mated in PW 16 -20.F2 rats were fed a standard diet fro m PW4 and rectal te mperature was measured in PW20,oral glucose tolerance test (OGTT)was con-ducted in PW21 ,blood sa mples and hypothala mus were collected in PW24 to investigate seru m lipids and HPA axis activity.RESULTS Co mparing to the F2 control group ,rectal te mperature in F2 ethanol group were higher (P<0.01 ),sugar tolerance in F2 male group was i mpaired (P<0.05),seru m corti-costerone and hypothala mus arginine vasopressin (AVP) mRNA were increased (P <0.05);seru m insulin were decreased (P<0.05)and male rats showed i mpaired glucose tolerance (P<0.05);seru m high-density lipoproteincholesterol (HDL-C)decrease (P <0.05)and total cholesterol (TCH)/HDL-C and low density lipoproteincholesterol (LDL-C)/HDL-C ratios were markedly increased (P <0.05,P <0.01 ).CONCLUSION Prenatal ethanol exposure induced metabolic syndro me has transgenerational effects,which may originate fro m the intrauterine progra mming of altered HPA axis-associated neuroen-docrine metabolis m.

Manufacture and clinical application of a external fixator for calcaneal fractures / 中华骨科杂志

Objective To evaluate the clinical results of indirect reduction and fixation with the self-manufactured external fixator as a viable alternative in the surgical treatment of intraarticular calcaneal fractures.Methods From May 2006 to May 2009,a total of 30 patients undergone surgical treatment of intraarticular calcaneal fractures were analyzed,including 20 males and 10 females with an average age of 36 years (range,15-53).According to Sanders classification based on the computed tomography scan of intraarticular calcaneal fractures,16 patients were classified as type-Ⅲ,and 14 type-Ⅳ in this series.All fractures were treated first with the external fixator as indirect reduction and fixation device on the whole,which can enlarge the interspace of the subtalar joint significantly.Then,posterior articular facet of calcaneus was exposed and reduced through a small lateral incision.The calcaneal's length,breadth,thalamus height,maximum vertical displacement of the post-articular surface,and B(o)hler angle were measured preoperatively,3 days and 6 months after operation in X-ray film.Reduction results were evaluated by CT scan according to the standard of Buckley.Results The average follow-up time of all patients was 29 months (range,4-45).Lateral and axial roentgenograms showed satisfactory restoration of the calcaneal's anatomical structure.There were significant differences between preoperative values and those 3 days or 6 months postoperatively.There were no significant differences between values 3 days postoperatively and those 6 months postoperatively.The reduction results of posterior articular facet were evaluated by CT scan.Twenty-seven patients obtained anatomical reduction,3 patients obtained uneven articular facet within 2 mm.Conclusion This selfmanufactured external fixator is a vialbe alternative in the treatment of intraarticular calcaneal fractures,which has advantages of minimal invasion,practicality and less complications.

Measurement of the bone mineral density in the tunnel region during the anterior cruciate ligament reconstruction / 中华骨科杂志

Objective To compare the bone mineral density of the regions of femoral and tibial tunnels for anterior cruciate ligament(ACL)reconstruction in order to provide reference for the choice of optimal screw diameter for interference fixation.Methods Thirty healthy volunteers aged from 18 to 35 years were enrolled in our study,and the dual-energy X-ray absorptiometry(DEXA)was used to measure the bone mineral density of femoral and tibial tunnel regions of the right knee.All the right knees of the volunteers were also scanned by spiral CT and three-dimensional reconstruction technique was utilized to determine the circular sections that pass through the longitudinal axis of the femoral and tibial tunnels separately.The CT gray scale values of the Sections were measured.From August to October 2010,9 patients who had been diagnosed as ACL rupture underwent the operation of ACL reconstruction,and cylindrical cancellous bone peg was removed from the femoral and tibial tunnel respectively during the operation.Volumetric bone mineral density of the bone pegs were measured by using a standardized immersion technique according to Archimedes’ principle.Results Measured by DEXA,bone density of the femoral tunnel region arid tibial tunnel region were(1.162±0.034)g/cm2 and(0.814±0.038)g/cm2 respectively.The difference was significant between the femoral and tibial tunnel region(t=9.11,P=0.000).The CT gray scale value of the section for femoral tunnel region was(211.7±11.5)Hu,while that of the tibial tunnel region was(104.9±7.4)Hu.There was statistically significant difference between them(t=10.15,P=0.000).The volumetric bone mineral density of the bone peg from femoral tunnel and tibial tunnel were(2.80±0.88)g/cm3 and(1.88±0.59)g/cm3 respectively.The difference was statistically significant(t=4.32,P=0.002).Conclusion For ACL reconstruction,bone mineral density of femoral tunnel region is higher than that of the tibial tunnel.

Effects of fluid shearing force on type Ⅱ collagen synthesis by human chondrocytes in vitro / 中华物理医学与康复杂志

Objective To detect type Ⅱ collagen synthesis by cultured human chondrocytes under the influence of different intermittent fluid shearing forces.Methods Second passage human monolayer chondrocytes were divided into low-speed (20 rpm/min), mid-speed (40 rpm/min) and high-speed (60 rpm/min) groups according to the rotation speed of the rocking bed. The expression of type Ⅱ collagen was analyzed using immunohistochemistry and RT-PCRs.Results The absorbance of the mid-speed and high-speed groups was significantly greater than that of the low-speed group and a control group. The average optical density of type Ⅱ collagen by RT-PCR was significantly higher in all three sheared groups than in the control group.Conclusions Intermittent shearing can enhance cellular proliferation and the metabolism of human chondrocytes in vitro and promote the expression of type Ⅱ collagen.

Effects of adenovirus-mediated bFGF, IL-1Ra and IGF-1 gene transfer on human osteoarthritic chondrocytes and osteoarthritis in rabbits

The study investigated the effects of adenovirus-mediated gene transfection of basic fibroblast growth factor (bFGF), bFGF combined with interleukin-1 receptor antagonist protein (IL-Ra) and/or insulin-like growth factor-1 (IGF-1) both in human osteoarthritis (OA) chondrocytes and rabbits OA model. Human OA chondrocytes were delivered by adenovirus-mediated bFGF, IL-Ra and IGF-1 vectors, respectively. Chondrocyte proliferation, glycosaminoglycan (GAG) content, expression of type II collagen, ADAMTS-5, MMP-13, MMP-3 and TIMP-1 were determined. Rabbit OA model was induced by anterior cruciate ligament transaction (ACLT) in knees. Adenoviral vectors encoding human bFGF, IL-Ra and IGF-1 were injected intraarticularly into the knee joints after ACLT. The effects of adenovirus- mediated gene transfection on rabbit OA were evaluated. In vitro, the transfected genes were expressed in cell supernatant of human OA chondrocytes. AdbFGF group significantly promoted chondrocyte proliferation, and increased GAG and type II collagen synthesis than in the OA group. As two or three genes were transfected in different combinations, there was significant enhancement on the GAG content, type II collagen synthesis, and TIMP-1 levels, while ADAMTS-5, MMP-13, and MMP-3 levels were reduced. In vivo, the transfected genes were expressed in synovial fluid of rabbits. Intraarticular delivery of bFGF enhanced the expression of type II collagen in cartilage and decreased cartilage Mankin score compared with the OA control group (P = 0.047; P < 0.01, respectively). Multiple-gene transfection in different combinations showed better results than bFGF transfection alone. This study suggests that bFGF gene transfection is effective in treating experimental OA. Multiple gene transfection has better biologic effects on OA.

Effects of adenovirus-mediated basic fibroblast growth factor and the related cytokines gene transfection on human osteoarthritis chondrocytes in vitro / 中华风湿病学杂志

Objective To investigate the effect of recombinant adenovirus-mediated basic fibroblast growth factor (bFGF),interleukin-1 receptor antagonist protein (IL-Ra) and insulin-like growth factor(IGF)-1 gene transfection on human osteoarthritis chondrocytes.Methods Monolayer cultures of human osteoarthritis chondrocytes were transfected with recombinant adenovirus carrying genes encoding the following cytokines: human bFGF,IL-1Ra and IGF-1.Six days later,levels of gene expression and glycosaminoglycan (GAG) in culture supernatant were detected.The proliferation and apoptosis of chondrocytes were analyzed by methyl thiazolyl tetrazolium (MTT) and flow cytometry respectively.Matrix biosynthesis was observed by toluidine blue staining and immunohistochemistry examination of type Ⅱ collagen.The expression of type Ⅱ collagen,MMP-3 and TIMP-1 were analyzed by immunoblotting.Comparisons between groups were performed with one-way ANOVA analysis.Results The expression of all transgenes was high following adenoviral transfection compared with the OA control group (P<0.05).The delivery of bFGF alone promoted the cell proliferation and resulted in a significant enhanced biosynthesis of type Ⅱ collagen and proteoglycans of chondrocytes (P<0.05).Compared with bFGF transfection alone,as two or three of the genes were transfected in different combinations,apoptosis rate of chondrocytes was decreased [(26.1±1.6)%,(19.4±1.0)%.(18.4±1.1)%,(13.9±1.8)%.respectively P<0.05].There was marked enhancement of matrix synthesis and expression of TIMP-1.At the same time,the expression of MMP-3 was inhibited.Conciuslon The bFGF gene transfection mediated with adenoviral vectors can greatly promote cell proliferation and increase matrix synthesis in vitro. Compared to the expression of bFGF alone, concomitant gene transfection of bFGF, IL-IRa and IGF-1 in different combinations plays a complementary role, further enhances matrix synthesis and inhibits matrix degradation.

Therapeutic effects of angelica and sodium ferulate on experimental osteoarthritis in rats / 中国矫形外科杂志

[Objective]To explore the therapeutic effects of angelica and sodium ferulate (SF) on experimental osteoarthritis and the related mechanisms in rats. [Method]Animal models of osteoarthritis were established in 40 rats by intra-articular injection of 4% papain. The rats were divided into five groups-model control group,25% and 5% angelica treatment groups, 0.5% and 0.1% SF treatment groups.Another additional 8 rats were used as normal control. Bilateral knees of the animalsin the treatment groups began receiving intra-articular injection of 0.1ml angelica injection or SF of corresponding concentration respectively every 3 days while those of the animals in the control groups received saline. All the animals were sacrificed 6 weeks later and samples of the cartilage, plasma and synovial fluid were taken. The contents of MDA and the activities of SOD in the plasma and synovial fluid were detected.Histological examinations of the cartilage were performed and immunohistochemical analyses for MMP-1, TIMP-1, Bcl-2 and Bax in the cartilage were done.[Result]25% Angelica and 0.5% SF significantly decreased the levels of MDA in both plasma and synovial fluid (P