The IFT80/Hedgehog Pathway Regulates the Osteogenic-adipogenic Differentiation of Bone Marrow Mesenchymal Stem Cells.

BACKGROUND: Steroid-induced avascular necrosis of the femoral head (SANFH) is a typical refractory disease that often progresses irreversibly and has a high disability rate. Numerous studies have confirmed that abnormal osteogenic-adipogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) is one of the major factors of SANFH. However, the mechanism remains to be elucidated. OBJECTIVES: This study aimed to investigate the mechanism and effect of the IFT80/Hedgehog-mediated osteogenic-adipogenic differentiation of BM-MSCs in SANFH. METHODS: Femoral head specimens of SANFH patients and femoral neck fractures (FNF) patients were collected to detect the expression of IFT80, Shh and osteogenic-adipogenic differentiation-related genes by immunohistochemistry (IHC), western blot (WB) and Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR). Based on the rabbit SANFH model, the mRNA expression and protein level of IFT80 and Shh were detected by RT-qPCR and WB. After the osteogenic/adipogenic differentiation based on rabbit BM-MSCs, the IFT80, Gli1, PPAR-γ, and Runx2 expression were detected. Differences in alkaline phosphodiesterase activity, calcium nodule, quantification/distribution of lipid droplets, expression of IFT80/Hedgehog axis, and the level of osteogenic- adipogenic associated factors were determined after IFT80 overexpression. RESULTS: RT-qPCR, WB and IHC revealed that IFT80 and Shh lowly expressed in the osteoblasts and intra-trabecular osteocytes at the edge of trabeculae and in the intercellular matrix of the bone marrow lumen in the SANFH specimens. The Runx2 expression was low, while the PPAR-γ expression was high in both human specimens and animal models of SANFH, suggesting that the balance of osteogenic-adipogenic differentiation was dysregulated. Rabbit BM-MSCs with stable overexpression of IFT80 showed increased alkaline phosphatase activity after induction of osteogenic differentiation, increased calcium nodule production, and decreased adipogenesis after induction of adipogenic differentiation. CONCLUSION: There is a dysregulation of the balance of osteogenic-adipogenic differentiation in SANFH. IFT80 may inhibit adipogenic differentiation while promoting osteogenic differentiation in rabbit BM-MSCs by activating the Hedgehog pathway.

Effects of external environment on promoter methylation of PIK3R5 and related pathway regulation in steroid-induced femoral head necrosis.

BACKGROUND: Steroid-induced Avascular Necrosis of the Femoral Head (SANFH) is a condition characterized by the necrosis of the femoral head caused by long-term or high-dose hormone usage. Studies have shown that the PI3K/AKT pathway plays a crucial regulatory role in the development of SANFH. The aim of this study is to determine how external environmental factors induce changes in endogenous hormone levels, how these changes lead to steroid-induced femoral head necrosis, and the interrelationship between the changes in PIK3R5 promoter methylation levels and the regulation of the associated signaling pathways. METHODS: Femoral head samples underwent molecular sequencing analysis. Candidate genes were screened by differential gene analysis and functional enrichment analysis.Methylation level of candidate gene PIK3R5 was verified by methylation-specific PCR(MS-PCR). SANFH model was constructed in New Zealand white rabbits, and the model results were verified by magnetic resonance imaging (MRI) and haematoxylin-eosin (HE) staining.The expression of PIK3R5, PI3K and AKT in rabbit models and human specimens was verified by real-time fluorescence quantitative PCR(RT-qPCR) and Western Blot(WB), respectively. RESULTS: Human femoral head sequencing results indicate distinct differences in the methylation level and mRNA expression of PIK3R5 in SANFH. MS-PCR results showed the methylation level of SANFH patients was significantly higher than that of the control group (P < 0.01). The RT-qPCR results showed that PIK3R5 and PI3K expression levels in the SANFH group were lower than those in the control group (P < 0.05), and the WB experiment results were consistent with the RT-qPCR results. The MRI and HE staining results showed that the rabbit model of SANFH was successfully constructed, and the results of RT-qPCR and WB were consistent with the results of human tissues. CONCLUSION: During the occurrence and development of SANFH, PIK3R5 gene regulates the PI3K/AKT pathway through methylation modification, promotes the oxidative stress response of cells, and accelerates the disease process.

Verification of cuproptosis-related diagnostic model associated with immune infiltration in rheumatoid arthritis.

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease closely related to inflammation. Cuproptosis is a newly discovered unique type of cell death, and it has been found that it may play an essential role in the occurrence and development of RA. Therefore, we intend to explore the potential association between cuproptosis-related genes (CRGs) and RA to provide a new biomarker for the treatment and prognosis of RA. Methods: Download GSE93777 datasets from the GEO database. Variance analysis was performed on the CRGs that had been reported. Then, the random forest (RF) model and nomogram of differentially expressed CRGs were constructed, and the ROC curve was used to evaluate the accuracy of the diagnostic model. Next, RA patients were subtyped by consensus clustering, and immune infiltration was analyzed in each subgroup to confirm the correlation between CRGs and abundance of immune cells. The expression levels of CRGs were verified by qRT-PCR. Results: Eight differentially expressed CRGs (DLST, DLD, PDHB, PDHA1, ATP7A, CDKN2A, LIAS, DLAT) were screened out by differential analysis to construct an RF model. The ROC curve proved that this model had good diagnostic accuracy. Based on the above eight significant CRGs, a nomogram was built to predict effective and high-precision results. The consensus clustering method identified two CRG patterns. Most of the immune cells were enriched in cluster A, indicating that cluster A may be related to the development of RA. Finally, qRT-PCR verified the expression of eight key genes, further confirming our findings. Conclusion: The diagnosis model of RA based on the above eight CRGs has excellent diagnostic potential. Based on these, patients can be divided into two different molecular subtypes; it is expected to develop a new treatment strategy for RA.

Exosome-mediated miR-144-3p promotes ferroptosis to inhibit osteosarcoma proliferation, migration, and invasion through regulating ZEB1.

BACKGROUND: Osteosarcoma (OS) is the most prevalent orthopedic malignancy with a dismal prognosis. The high iron absorption rate in OS cells of patients suggests that ferroptosis may be related to the progression of OS, but its potential molecular regulatory role is still unclear. Based on the ability to couple with exosomes for targeted delivery of signals, exosome-derived micro ribonucleic acids (miRNAs) can potentially serve as diagnostic biomarkers for OS. METHODS: We identified ferroptosis-related miRNAs and messenger ribonucleic acids(mRNAs) in OS using bioinformatics analysis and performed survival analysis. Then we measured miRNA expression levels through exosome microarray sequencing, and used RT-qPCR and IHC to verify the expression level of miR-144-3p and ZEB1. Stable gene expression cell lines were fabricated for in vitro experiments. Cell viability, migration and invasion were determined by CCK-8 and transwell experiment. Use the corresponding reagent kit to detect GSH/GSSG ratio, Fe2+ level, MDA level and ROS level, and measure the expression levels of GPX4, ACSL4 and xCT through RT-qPCR and WB. We also constructed nude mice model for in vivo experiments. Finally, the stability of the miRNA/mRNA axis was verified through functional rescue experiments. RESULTS: Low expression of miR-144-3p and high expression of ZEB1 in OS cell lines and tissues was observed. Overexpression of miR-144-3p can promote ferroptosis, reduce the survival ability of OS cells, and prevent the progression of OS. In addition, overexpression of miR-144-3p can downregulate the expression of ZEB1 in cell lines and nude mice. Knockdown of miR-144-3p has the opposite effect. The functional rescue experiment validated that miR-144-3p can regulate downstream ZEB1, and participates in the occurrence and development of OS by interfering with redox homeostasis and iron metabolism. CONCLUSIONS: MiR-144-3p can induce the occurrence of ferroptosis by negatively regulating the expression of ZEB1, thereby inhibiting the proliferation, migration, and invasion of OS cells.

Verification of Ferroptosis Subcluster-Associated Genes Related to Osteosarcoma and Exploration of Immune Targeted Therapy.

Background: Despite tremendous advances in treating osteosarcoma (OS), the survival rates of patients have failed to improve dramatically over the past decades. Ferroptosis, a newly discovered iron-dependent type of regulated cell death, is implicated in tumors, and its features in OS remain unascertained. We designed to determine the involvement of ferroptosis subcluster-related modular genes in OS progression and prognosis. Methods: The OS-related datasets retrieved from GEO and TARGET database were clustered for identifying molecular subclusters with different ferroptosis-related genes (FRGs) expression patterns. Weighted gene coexpression network analysis (WGCNA) was applied to identify modular genes from FRG subclusters. The least absolute shrinkage and selection operator (LASSO) algorithm and multivariable Cox regression analysis were adopted to develop the prognostic model. Potential mechanisms of development and prognosis in OS were explored by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA). Then, a comprehensive analysis was conducted for immune checkpoint markers and assessment of predictive power to drug response. The protein expression levels of the three ferroptosis subcluster-related modular genes were verified by immunohistochemistry. Results: Two independent subclusters presenting diverse expression profiles of FRGs were obtained, with significantly different survival states. Ferroptosis subcluster-related modular genes were screened with WGCNA, and the GESA results showed that ferroptosis subcluster-related modular genes could affect the cellular energy metabolism, thus influencing the development and prognosis of osteosarcoma. A prognostic model was established by incorporating three ferroptosis subcluster-related modular genes (LRRC1, ACO2, and CTNNBIP1) and a nomogram by integrating clinical features, and they were evaluated for the predictive power on OS prognosis. The 20 immune checkpoint-related genes confirmed the insensitivity to tumor immunotherapy in high-risk patients. IC50s of Axitinib and Cytarabine suggested a higher sensitivity to the targeted drug. Finally, the quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry were consistent with bioinformatics analysis. Conclusion: Ferroptosis are closely associated with the OS prognosis. The risk-scoring model incorporating three ferroptosis subcluster-related modular genes has shown outstanding advantages in predicting patient prognosis.

Identification of Potential Therapeutic Target Genes in Osteoarthritis.

Objective: Osteoarthritis (OA), also known as joint failure, is characterized by joint pain and, in severe cases, can lead to loss of joint function in patients. Immune-related genes and immune cell infiltration play a crucial role in OA development. We used bioinformatics approaches to detect potential diagnostic markers and available drugs for OA while initially exploring the immune mechanisms of OA. Methods: The training set GSE55235 and validation set GSE51588 and GSE55457 were obtained from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified by the limma package. Gene set enrichment analysis (GSEA) was performed on the GSE55235 dataset using the cluster profiler package. At the same time, DEGs were analyzed by gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). In addition, protein-protein interaction (PPI) analysis was performed on the common DEGs of the three datasets using the STRING database. Proteins with direct linkage were identified as hub genes, and the relation of hub genes was subsequently analyzed using the GOSemSim package. Hub genes' expression profiles and diagnostic capabilities (ROC curves) were analyzed and validated using three datasets. In addition, we performed RT-qPCR to validate the levels of hub genes. The immune microenvironment was analyzed using the CIBERSORT package, and the relationship between hub genes and immune cells was evaluated. In addition, we used a linkage map (CMAP) database to identify available drug candidates. Finally, the GSEA of hub genes was used to decipher the potential pathways corresponding to hub genes. Results: Three hub genes (CX3CR1, MYC, and TLR7) were identified. CX3CR1 and TLR7 were highly expressed in patients with OA, whereas the expression of MYC was low. The results of RT-qPCR validation were consistent with those obtained using datasets. Among these genes, CX3CR1 and TLR7 can be used as diagnostic markers. It was found that CX3CR1, MYC, and TLR7 affect the immune microenvironment of OA via different immune cells. In addition, we identified a potential drug for the treatment of OA. Altogether, CX3CR1, MYC, and TLR7 affect the immune response of OA through multiple pathways. Conclusion: CX3CR1, MYC, and TLR7 are associated with various immune cells and are the potential diagnostic markers and therapeutic targets for OA.

Predicting the Risk of Diabetic Foot Ulcers From Diabetics With Dysmetabolism: A Retrospective Clinical Trial.

Background: Diabetic foot ulcer (DFU) in patients with type 2 diabetes mellitus (T2D) often leads to amputation. Early intervention to prevent DFU is urgently necessary. So far, there have been no studies on predictive models associated with DFU risk factors. Our study aimed to quantify the predictive risk value of DFU, promote health education, and further develop behavioral interventions to reduce the incidence of DFU. Methods: Data from 973 consecutive patients with T2D was collected from two hospitals. Patients from the Guangxi Medical University First Affiliated Hospital formed the training cohort (n = 853), and those from the Wuming Hospital of Guangxi Medical University formed the validation cohort (n = 120). Independent variable grouping analysis and multivariate logistic regression analysis were used to determine the risk factors of DFUs. The prediction model was established according to the related risk factors. In addition, the accuracy of the model was evaluated by specificity, sensitivity, predictive value, and predictive likelihood ratio. Results: In total, 369 of the 853 patients (43.3%) and 60 of the 120 (50.0%) were diagnosed with DFUs in the two hospitals. The factors associated with DFU were old age, male gender, lower body mass index (BMI), longer duration of diabetes, history of foot disease, cardiac insufficiency, no use of oral hypoglycemic agent (OHA), high white blood cell count, high platelet count, low hemoglobin level, low lymphocyte absolute value, and high postprandial blood glucose. After incorporating these 12 factors, the nomogram drawn achieved good concordance indexes of 0.89 [95% confidence interval (CI): 0.87 to 0.91] in the training cohort and 0.84 (95% CI: 0.77 to 0.91) in the validation cohort in predicting DFUs and had well-fitted calibration curves. Patients who had a nomogram score of ≥180 were considered to have a low risk of DFU, whereas those having ≥180 were at high risk. Conclusions: A nomogram was constructed by combining 12 identified risk factors of DFU. These 12 risk factors are easily available in hospitalized patients, so the prediction of DFU in hospitalized patients with T2D has potential clinical significance. The model provides a reliable prediction of the risk of DFU in patients with T2D.

A Risk-Scoring Model Based on Evaluation of Ferroptosis-Related Genes in Osteosarcoma.

Background: Osteosarcoma (OS) is a bone malignancy frequently seen in pediatrics and has high mortality and incidence. Ferroptosis is an important cell death process in regulating the apoptosis and invasion of tumor cells, so constructing the risk-scoring model based on OS ferroptosis-related genes (FRGs) will benefit the evaluation of both treatment and prognosis. Methods: The OS dataset was screened from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database, and OS-related FRGs were found through the Ferroptosis Database (FerrDb) using a multivariate Cox regression model, followed by the generation of the risk scores and a risk-scoring prediction model. Further systematical exploration for immune cell infiltration and assessing the prediction of response to targeted drugs was conducted. Results: Based on OS-related FRGs, a risk-scoring model of FRGs in OS was constructed. The six FRGs played a role in the carbon metabolism, glutathione metabolism, and pentose phosphate pathways. Results from targeted drug sensitivity analyses were concordant to pathway analyses. The response to targeted drugs statistically differed between the two groups with different risks, and the high-risk group presented a high sensitivity to targeted drugs. Conclusions: We identified a 6-ferroptosis-gene-based prognostic signature in OS and created and verified a risk-scoring model to predict the prognosis of OS at 1, 3, and 5 years for OS patients independently.

Risk score model of autophagy-related genes in osteosarcoma.

Background: Osteosarcoma (OS) is a common pediatric malignancy with high mortality and disability rates. Autophagy is an essential process in regulating the apoptosis and invasion of tumor cells, so constructing a risk score model of OS autophagy-related genes (ARGs) will bring benefit to the evaluation of both treatment and prognosis. Methods: We downloaded a dataset of OS from the Therapeutically Applicable Research To Generate Effective Treatments (TARGET) database, and found OS-related ARGs through the Human Autophagy Database (HADb). Five hub ARGs (CCL2, AMBRA1, VEGFA, MYC and EGFR) were obtained using a multivariate Cox regression model. We then generated the risk scores and constructed a prediction model. Another dataset obtained from the Gene Expression Omnibus (GEO) was used to test accuracy and validity. The role of immune cell infiltration was systematically explored, and prediction of response to targeted drugs was assessed. Immunohistochemistry was carried out to verify the expression of the key ARGs. Results: Based on the five hub ARGs, we established a risk score model related to OS. High accuracy and validity were demonstrated by datasets downloaded from the GEO. The five ARGs played a role in the PI3K and MAPK pathways. Results from targeted drug sensitivity analyses were consistent with pathway analyses. Immunohistochemistry demonstrated that the expression differences of the five ARGs were significant between the OS group and the paracancerous group. Conclusions: We constructed a risk score model related to autophagy of OS, explored the diagnostic value of ARGs, and present possible therapeutic targets.

The efficacy and safety of fast track surgery (FTS) in patients after hip fracture surgery: a meta-analysis.

BACKGROUND: Fast track surgery (FTS) has been gradually applied in perioperative management of orthopedic surgery, but there still some research suspected that the prognosis of patients is not as expected and the cost is high, the effect of the FTS still urgently needed for support by evidence-based medicine. METHODS: We retrieved RCTs from medical research literature databases. Risk ratios (RR), standard mean difference (SMD), and 95% confidence intervals (CI) were calculated to compare the primary and safety endpoints. RESULTS: Overall, a total of 8886 patients were retrieved from 57 articles, of which 4448 patients (50.06%) were randomized to experimental group whereas 4438 patients (49.94%) were randomized to control group. The result showed that FTS could significantly shorten the length of stay (LOS), decrease the visual analog scale (VAS), reduce the leaving bed time and the hospitalization costs, and improve Harris hip joint function score. The incidence of complications such as respiratory system infection, urinary system infection, venous thrombus embolism (VTE), pressure sore, incision infection, constipation, and prosthesis dislocation also has been decreased significantly. Meanwhile, FTS improved patients' satisfaction apparently. CONCLUSIONS: This meta-analysis reveals that FTS could significantly shorten the length of stay, alleviate the pain, reduce the leaving bed time and the hospitalization costs, and improve hip function. The incidence of complications also has been decreased significantly. Meanwhile, FTS has been spoken highly in patients in terms of nursing satisfaction. Its efficacy and safety were proved to be reliable.

The efficacy and safety of selective COX-2 inhibitors for postoperative pain management in patients after total knee/hip arthroplasty: a meta-analysis.

BACKGROUND: Many selective cyclooxygenase (COX-2) inhibitors are currently used in clinical practice. COX-2 inhibitors have good anti-inflammatory, analgesic, antipyretic effects, and gastrointestinal safety. However, the analgesic effects and adverse reactions of COX-2 after total knee/hip arthroplasty (TKA/THA) are not fully known. OBJECTIVE: To evaluate the efficacy and safety of selective COX-2 inhibitors in postoperative pain management in patients receiving TKA/THA. METHODS: Randomized controlled trials (RCTs) were retrieved from medical literature databases. Risk ratios (RR) Std mean difference (SMD) and 95% confidence intervals (CI) were calculated to analyze the primary and safety endpoints. RESULTS: In total, 18 articles (23 trial comparisons) were retrieved comprising 3104 patients. Among them, 1910 patients (61.5%) were randomized to the experimental group whereas 1194 patients (38.5%) were randomized to the control group. The primary endpoints were the patients' VAS score at rest or on ambulation (within 3 days). We found that VAS score in patients that received selective COX-2 inhibitor was significantly lower compared to those of the control group. CONCLUSION: This meta-analysis shows that selective COX-2 inhibitor therapy is effective, safe, and reliable in relieving postoperative pain of THA/TKA.

Impaired osteogenic differentiation associated with connexin43/microRNA-206 in steroid-induced avascular necrosis of the femoral head.

Connexin(Cx)43 and microRNA(miR)-206 play an important role in osteogenesis. However, their role in steroid-induced femoral head osteonecrosis (SANFH) is still ambiguous. The present study aimed to establish a rabbit model and investigate osteogenesis in steroid-induced femoral head osteonecrosis occurring via Cx43/miR-206 and the changes of Wnt/ß-catenin signal pathway-related proteins. A total of 72 adult New Zealand white rabbits were divided randomly into a model group (Group A) and a control group (Group B) of 36 rabbits each. Group A was injected intravenously with lipopolysaccharide (10µg/kg body weight, once per day). After 48h, three injections of methylprednisolone (MPS; 20mg/kg body weight) were administered intramuscularly at 24-hour intervals. Group B were fed and housed under identical conditions but received saline injections. All animals were sacrificed at two, four, and eight weeks from the first MPS injection. Typical early osteonecrosis symptoms were observed in Group A. The expression of miR-206 in Group A was significantly higher than that of Group B. The mRNA and protein levels of Cx43, ß-catenin, runt-related transcription factor 2, and alkaline phosphatase gradually decreased while Dickkopf-1 (Dkk-1) gradually increased in Group A compared with Group B. These findings indicated that Cx43/miR-206 is involved in the pathogenesis of early stage SANFH and may be associate with Wnt/ß-catenin signal pathway.

Effects of exercise training on depression in patients with heart failure: a systematic review and meta-analysis of randomized controlled trials.

AIMS: The aim of this review is to assess the effects of exercise training on the symptoms of depression in heart failure (HF) patients. METHODS AND RESULTS: Randomized controlled trials of exercise training in patients with HF and symptoms of depression were identified. The depression data were pooled using meta-analysis, and 19 studies were identified, with a total of 3447 patients, of which 16 (3226 patients) provided data for the meta-analysis. Exercise training demonstrated significant reductions in the symptoms of depression [standardized mean difference (SMD) -0.38, 95% confidence interval (CI) -0.55 to -0.21], and its antidepressive effect was consistent in a number of HF groups, such as in ages under and over 65 years (SMD -0.14, 95% CI -0.22 to -0.07 vs. SMD -0.44, 95% CI -0.61 to -0.27) and EFs of <50% (SMD -0.38, 95% CI -0.56 to -0.20), as well as in a range of interventional strategies, including the aerobic mode (SMD -0.40, 95% CI -0.61 to -0.19), centre, home, or combined setting (SMD -0.61, 95% CI -0.95 to -0.27 vs. SMD -0.25, 95% CI -0.44 to -0.07 vs. SMD -0.13, 95% CI -0.21 to -0.05), and short or longer training programmes (≤12 weeks, SMD -0.50, 95% CI -0.73 to -0.27; 12-26 weeks, SMD -0.47, 95% CI -0.82 to -0.11; >26 weeks, SMD -0.12, 95% CI -0.20 to -0.04). The beneficial effects were preserved when blind design trials were considered (SMD -0.14, 95% CI -0.22 to -0.07). CONCLUSION: Exercise training significantly decreased the symptoms of depression in patients with HF. This benefit remained unclear in cases of HF with a normal EF and combined aerobic and strength training. Random controlled trials are needed to verify the benefit of exercise in these populations, and in very old, asymptomatic, and severe HF patients.

Mobile bearing or fixed bearing? A meta-analysis of outcomes comparing mobile bearing and fixed bearing bilateral total knee replacements.

BACKGROUND: To compare outcomes between mobile-bearing (MB) and fixed-bearing (FB) in bilateral total knee replacements. METHODS: The MEDLINE, EMBASE and Cochrane Library databases were searched. Randomized controlled trials of bilateral total knee arthroplasty with one of each design implanted were identified. Weighted mean differences (WMDs) and pooled risk ratios (RRs) were calculated using fixed- or random-effects models. RESULTS: Twelve studies were identified with a total of 807 patients and 1614 knees. All RCTs were of high quality with a low risk of bias. No statistical difference was found between MB and FB at 2- to 5-year follow-up in terms of America Knee Society score (WMD: -1.29, 95% CI: -5.65 to 3.06), pain score (WMD: -3.26, 95% CI: -10.45 to 3.93), range of motion (WMD: -4.16, 95% CI: -9.97 to 1.66), reoperation (RR: 1.00, 95% CI: 0.28 to 3.60), and radiolucent lines (RR: 1.51, 95% CI: 0.70 to 3.24). The results were similar at 1-, 5- to 8-, or >8-year follow-up. Patient's satisfaction (RR: 0.85, 95% CI: 0.54 to 1.34), and complication (≤2-year, RR: 0.55, 95% CI: 0.29 to 1.04; >2-year, RR: 1.0, 95% CI=0.73 to 1.38) also showed no difference between two groups. CONCLUSIONS: Based on this meta-analysis we are unable to detect the superiority of MB as compared to FB. More randomized trials with a larger sample size and longer follow-up are needed to evaluate these two kinds of prosthesis. LEVEL OF EVIDENCE: Therapeutic Level II.

A meta-analysis of hamstring autografts versus bone-patellar tendon-bone autografts for reconstruction of the anterior cruciate ligament.

The objective of this study was to evaluate the effectiveness of hamstring (HT) autografts versus bone-patellar tendon-bone (BPTB) autografts for reconstruction of the anterior cruciate ligament (ACL). We searched the Cochrane Library, MEDLINE, EMBASE and the Chinese Biomedicine Database (CBM) for published randomised clinical trials (RCTs) relevant to ACL reconstruction comparing HT and BPTB autografts. Data analyses were performed with Cochrane Collaboration's RevMan 5.0. A total of 23 reports of 19 randomised controlled trials (RCTs) (1643 patients) met the inclusion criteria. Outcomes favouring BPTB autografts were found in terms of KT-1000 arithmometer values, negative rates of Lachman tests and negative rates of Pivot tests. Outcome measures that favoured HT autografts included anterior knee pain, kneeling pain and extension loss. There was no statistical difference of postoperative graft failure. Overall, postoperative complications of the knee joint were lower for HT autografts than for BPTB autografts, and BPTB autografts were superior to HT autografts in resuming stability of the knee joint, but four-strand HT combined with application of the modern endobutton HT graft-fixation technique could increase knee-joint stability.

[Progress of peripheral nerve defect treatment with tissue engineering].

OBJECTIVE: To review new progress of related research of peripheral nerve defect treatment with tissue engineering in recent years. METHODS: Domestic and international literature concerning peripheral nerve defect treatment with tissue engineering was reviewed and analyzed. RESULTS: Releasing neurotrophic factors with sustained release technology included molecular biology techniques, poly (lactic-co-glycolic acid) microspheres, and polyphosphate microspheres. The mixture of neurotrophic factors and ductus was implanted to the neural tube wall which could be degraded then releasing factors slowly. Seed cells which were the major source of active ingredients played an important role in the repair and reconstruction of tissue engineering products. The neural tube of Schwann cells made long nerve repair and the quality of nerve regeneration was improved. Nerve scaffold materials included natural and synthetic biodegradable materials. Tube structure usually was adopted for nerve scaffold, which performance would affect the nerve repair effects directly. CONCLUSION: With the further research of tissue engineering, the treatment of peripheral nerve defects with tissue engineering has made significant progress.

[Study on effect of NGF on fracture healing].

OBJECTIVE: To investigate the effect of NGF on fracture healing, and to study the role of BMP-2 induced osteoblast. METHODS: Sixty cleaned male Kunming mice (aging 6-8 weeks and weighing 23-25 g) were made fracture models in the middle of femoral shaft and randomly divided into four groups (groups A, B, C and D, n=15). Fracture was treated with NGF/normal saline, BMP-2, BMP-2/NGF/normal saline, and normal saline in groups A, B, C and D, respectively. After 14, 21 and 28 days, the specimens were selected from 5 mice each group to do the biochemical and histological analysis. Before the mice were killed, the arteriovenous blood was taken from their eye-ball to test the ALP activity. RESULTS: After 14 days, 21 days and 28 days, the gross observation showed that the size and hardness of bone tissue, and callus tissue growth increased in groups A, B and C order and were higher than those in group D; the X-ray films showed that the calcified area increased in groups A, B and C order and were higher than those in group D; the histological observation showed that the trabecular maturity increased in groups A, B and C order and were higher than those in group D. The osteoblast area, the gray degree value of the radiographs in callus tissue, the ALP contents of serum and callus tissue, calcium content of callus tissue and net weight of callus were higher in groups A, B and C than in group D. There were significant differences (P < 0.05) in osteoblast area and gray degree values of the radiographs at 14, 21 and 28 days; in ALP contents of serum at 14 days; in ALP contents of callus tissue at 14 days and 21 days; in calcium content of callus tissue at 21 days and 28 days among 4 groups. There were significant differences in net weight of callus between groups B, C and groups A, D at 14 days (P < 0.05). At 21 days and 28 days, the trabecular surface index of osteoblast, the average trabecular volume and the mean trabecular width decreased as time went on, having an increase order of groups A, B, C and was higher in groups A, B, C than in group D, showing significant differences among 4 groups (P < 0.05). CONCLUSION: NGF promotes the healing of fractures. NGF possesses synergistic effect on ectopic bone formation induced by BMP-2.