The role of macrophage polarization in tendon healing and therapeutic strategies: Insights from animal models.

Tendon injuries, a common musculoskeletal issue, usually result in adhesions to the surrounding tissue, that will impact functional recovery. Macrophages, particularly through their M1 and M2 polarizations, play a pivotal role in the inflammatory and healing phases of tendon repair. In this review, we explore the role of macrophage polarization in tendon healing, focusing on insights from animal models. The review delves into the complex interplay of macrophages in tendon pathology, detailing how various macrophage phenotypes contribute to both healing and adhesion formation. It also explores the potential of modulating macrophage activity to enhance tendon repair and minimize adhesions. With advancements in understanding macrophage behavior and the development of innovative biomaterials, this review highlights promising therapeutic strategies for tendon injuries.

Risk factors for redislocation of chronic Monteggia fracture-dislocation in children after reconstruction surgery.

INTRODUCTION: Monteggia fracture-dislocation refers to traumatic ulnar fractures and dislocation of the radial head, which is one of the most frequently missed injuries, especially in children. The most widespread attitude towards chronic Monteggia lesion is the open reduction of the radial head associated with ulnar osteotomy with or without annular ligament reconstruction. Our study aimed to analyze the risk factors for redislocation after surgical management of chronic Monteggia lesion and the benefits of annular ligament reconstruction and radiocapitellar pinning in paediatric. MATERIALS AND METHODS: We retrospectively reviewed patients treated with reconstruction surgery for chronic Monteggia fracture-dislocation in our department between 2005 and 2017, with a minimum two years' follow-up. The reconstruction surgery included ulnar osteotomy performed in all patients, annular ligament repair or reconstruction or fixation of radiocapitellar joint, or radial osteotomy in some patients. We collected the related clinical data and evaluated the risk factors of redislocation using logistic regression analyses and a two-piecewise linear regression model with a smoothing function, after reconstruction. RESULTS: Throughout a mean six years' follow-up (range, 2-14 years), 62 patients (42 males, 20 females; average age 6.49 years range, 2-13 years) were reviewed. Of the radiocapitellar joints, 16.1% was noted to have redislocation. Univariate risk analysis showed age, time from injury to surgery, and radial osteotomy were risk factors for a recurrent radiocapitellar redislocation. Time from injury to surgery was found to be independent predictor of redislocation in multivariate analysis. However, there were significant nonlinear associations between time from injury to surgery and redislocation in multivariate logistic regression analysis after multivariate adjustment (p for nonlinear = 0.023). Every one month increase was associated with a 1.37-fold increase in redislocation, in participants within one year after injury. CONCLUSION: In conclusion, the surgery of chronic Monteggia fracture-dislocation should be done as quickly as possible within one year after injury. Associated annular ligament reconstruction or fixation of radiocapitellar joint does not seem to be helpful.

The Effect of Stromal-Derived Factor 1α on Osteoinduction Properties of Porous ß-Tricalcium Phosphate Bioceramics.

ß-Tricalcium phosphate (TCP) is a type of bioceramic material which is commonly used for hard tissue repair and famous of its remarkable biocompatibility and osteoconductivity with similar composition to natural bone. However, TCP lacks osteoindcutive properties. Stromal-derived factor 1α (SDF-1α) can promote bone regeneration with excellent osteoinduction effect. In this study, SDF-1α was loaded into TCP to investigate the in vitro effects of SDF-1α on the osteoinductive properties of TCP. In vitro studies showed that SDF-1α/TCP scaffold significantly stimulated the expression of osteopontin and osteocalcin. As to the in vivo studies, the rabbit bone defect model showed that SDF-1α stimulated more new bone formation. In conclusion, SDF-1α/TCP bioceramic scaffolds could further promote bone regeneration compared to pure TCP bioceramics.

Finite element and biomechanical analysis of risk factors for implant failure during tension band plating.

OBJECTIVE: Tension band plating has recently gained widespread acceptance as a method of correcting angular limb deformities in skeletally immature patients. We examined the role of biomechanics in procedural failure and devised a new method of reducing the rate of implant failure. METHODS: In the biomechanical model, afterload (static or cyclic) was applied to each specimen. The residual stress of the screw combined with different screw sizes and configurations were measured and compared by X-ray diffraction. With regard to static load and similar conditions, the stress distribution was analyzed according to a three-dimensional finite element model. RESULTS: The residual stress was close to zero in the static tension group, whereas it was very high in the cyclic load group. The residual stress of screws was significantly lower in the convergent group and parallel group than in the divergent group. The finite element model showed similar results. CONCLUSIONS: In both the finite element analysis and biomechanical tests, the maximum stress of the screw was concentrated at the position where the screws enter the cortex. Cyclic loading is the primary cause of implant failure.

Integrated bioinformatics analysis of potential pathway biomarkers using abnormal proteins in clubfoot.

BACKGROUND: As one of the most common major congenital distal skeletal abnormalities, congenital talipes equinovarus (clubfoot) affects approximately one in one thousandth newborns. Although several etiologies of clubfoot have been proposed and several genes have been identified as susceptible genes, previous studies did not further explore signaling pathways and potential upstream and downstream regulatory networks. Therefore, the aim of the present investigation is to explore abnormal pathways and their interactions in clubfoot using integrated bioinformatics analyses. METHODS: KEGG, gene ontology (GO), Reactome (REAC), WikiPathways (WP) or human phenotype ontology (HP) enrichment analysis were performed using WebGestalt, g:Profiler and NetworkAnalyst. RESULTS: A large number of signaling pathways were enriched e.g. signal transduction, disease, metabolism, gene expression (transcription), immune system, developmental biology, cell cycle, and ECM. Protein-protein interactions (PPIs) and gene regulatory networks (GRNs) analysis results indicated that extensive and complex interactions occur in these proteins, enrichment pathways, and TF-miRNA coregulatory networks. Transcription factors such as SOX9, CTNNB1, GLI3, FHL2, TGFBI and HOXD13, regulated these candidate proteins. CONCLUSION: The results of the present study supported previously proposed hypotheses, such as ECM, genetic, muscle, neurological, skeletal, and vascular abnormalities. More importantly, the enrichment results also indicated cellular or immune responses to external stimuli, and abnormal molecular transport or metabolism may be new potential etiological mechanisms of clubfoot.

The effect of temporary hemiepiphysiodesis in the treatment of skeleton immature posttraumatic genu angular deformity: a retrospective study of 27 cases.

BACKGROUND: The purpose of this study was to evaluate the effect, rate of angular correction, and complications of temporary hemiepiphysiodesis (TH) in the treatment of skeleton immature posttraumatic genu angular deformity. METHODS: We retrospectively reviewed the records of 27 patients undergoing temporary hemiepiphysiodesis for the management of posttraumatic genu angular deformity. Based on the data from these patients, the rate of correction, effect of correction, length of the lower limbs, and complications were used as the outcome measures. RESULTS: Outcome measurements were obtained from a chart review of medical records that included information about clinical evaluations. Fifteen boys and 12 girls, with an average age of 6.3 years, were included in the study. The average follow-up was 3.8 years (range, 1.9 to 5.9 years) after surgery. Complete correction was obtained in 24 patients, while partial correction was obtained in 3 patients. The mean rate of angular correction was 8.41°/year in distal femur and 15.19°/year in proximal tibia. One patient had recurrence of genu valgum. No leg length discrepancy was found in our patients. CONCLUSION: Temporary hemiepiphysiodesis is a simple, effective, reliable, and reproducible method for the treatment of posttraumatic genu angular deformity, with fewer complications than osteotomy. Nevertheless, it is important to follow the rebound patient closely until skeletal maturity in our future work.

Hemiepiphysiodesis stapling induces ER stress apoptosis and autophagy in rat growth plates.

Angular deformities of adolescents can be treated with temporary hemiepiphysiodesis. It is confirmed that mechanical staples leading to apoptosis of chondrocyte in the growth plate. In addition, clinical evidences revealed that release from growth-inhibition condition resulted in catch-up growth, which caused damage to the patients. Thus, the current study aimed to investigate the mechanisms underlying the cell growth inhibition and the rebound growth during the temporary hemiepiphysiodesis on the growth plate. Rats with knee stapling were housed for indicated weeks, then were separated into control group, hemiepiphysiodesis groups and removal of staple groups. The tissue samples were analyzed by histopathological staining or western blotting. The results indicated there was significant growth arrest and cell apoptosis in rats treated with mechanical stress loaded (hemiepiphysiodesis group). Additionally, immunohistochemistry staining and western blotting revealed the ER-stress induced cell apoptosis was involved in growth inhibition. In removal of staple group, growth-inhibition, apoptotic cells, ER stress and autophagy-related markers were all decreased when the staples were removed from mice. Moreover, IκB/NF-κB pathway were activated in the growth plate of rats when the loads were released. In conclusion, mechanical load leaded to growth inhibition in the growth plate. ER-stress induced apoptosis and autophagy might be responsible for this process. In contrast, the possible reason for the rebound growth of growth plate may be due to the elevated IκB/NF-κB activity.

Microarray study of gene expression profile to identify new candidate genes involved in the molecular mechanism of leptin-induced knee joint osteoarthritis in rat.

BACKGROUND: Osteoarthritis (OA) is one of the most prevalent chronic joint diseases while the precise genetic mechanism remains elusive. In this study, we investigated the gene expression profile in OA by microarray analysis. RESULTS: Histopathological characteristics of OA cartilage were examined using a rat model of leptin-induced OA. Gene expression profile of leptin-induced articular cartilage and healthy rat cartilage were compared using genome-wide microarray hybridization. A total of 1857 genes differentially expressed genes (1197 upregulated and 660 downregulated) were identified, some of which are known to be associated with leptin-induced OA phenotype. These included genes related to MMPs, inflammatory factors, growth factors, apoptotic genes and osteogenic genes. In addition, upregulated expressions of some new candidate genes, which have hitherto fore not been linked to OA (such as BCL2L11) were detected in leptin-induced OA cartilage, which suggests that these genes might be important for OA molecular mechanism. CONCLUSION: Our findings suggest that pathogenesis of leptin-induced OA involves modulation of expression of multiple genes, although the underlying molecular mechanisms need to be studied further. Further investigation of leptin-induced gene expression changes is needed to gain new insights into the molecular mechanism of OA pathogenesis.

Effect of Hemiepiphysiodesis on the Growth Plate: The Histopathological Changes and Mechanism Exploration of Recurrence in Mini Pig Model.

PURPOSE: Hemiepiphysiodesis has been widely used to correct angular deformity of long bone in immature patients. However, there is a limited knowledge about the biomechanical effect of this technique on the histopathological changes of the growth plate and the mechanism of recurrence of malformation after implant removal. We aimed to evaluate the biomechanical effect of hemiepiphysiodesis on the histopathological changes of the growth plate and the mechanism of recurrence of malformation after implant removal in Bama miniature pigs, and to explore the role of asymmetric stress during this procedure. METHODS: Eight 3-month-old male Bama miniature pigs sustained surgeries on the bilateral medial hind leg proximal tibia as the intervention group (n=16), and four pigs sustained bilateral sham surgeries as the control (n=8). In the 18th week after surgeries, hardware was removed in the unilateral leg of each animal in the intervention group. In the 24th week of the study, all animals were euthanized. A total of 24 samples were obtained and stained with H&E, TUNEL, and immunohistochemistry. Sixteen samples in the intervention group were divided into two subgroups. The tibias without an implant were included in the implant removal group (IR group), while the tibias with an implant were included in the implant persist group (IP group). The proximal tibia specimens were divided into 3 equidistant parts from medial to lateral, named as area A, area B, and area C, respectively. The change of thickness of growth plates, chondral apoptosis index, and the expression of Caspase-3, Caspase-9, CHOP, and P65 were compared. RESULTS: H&E staining showed the thickness of growth plate to be varied in different areas. In the IP group, the thickness of growth plate in areas A and B was statistically significantly thinner than that in area C (p<0.05). In the IR group, the thickness of growth plate in areas A and B was statistically significantly thicker than that in area C (p<0.05). TUNEL staining showed that the apoptosis rate increased significantly after hemiepiphysiodesis and declined after implant removal (p<0.05). Immunohistochemical staining suggested that the expression of Caspase-3, Caspase-9, P65, and CHOP protein was upregulated in the experimental group and downregulated after implant removal. CONCLUSION: The thickness parameter of the growth plate changes with asymmetric pressure. When the pressure is relieved, the recurrence of malformation is related to the thickening of the growth plate.

Targeting Notch1 signaling pathway positively affects the sensitivity of osteosarcoma to cisplatin by regulating the expression and/or activity of Caspase family.

BACKGROUND: The introduction of cisplatin has improved the long-term survival rate in osteosarcoma patients. However, some patients are intrinsically resistant to cisplatin. This study reported that the activation of Notch1 is positively correlated with cisplatin sensitivity, evidenced by both clinical and in vitro data. RESULTS: In this study, a total 8 osteosarcoma specimens were enrolled and divided into two groups according to their cancer chemotherapeutic drugs sensitivity examination results. The relationship between Notch1 expression and cisplatin sensitivity of osteosarcoma patients was detected by immunohistochemistry and semi-quantitative analysis. Subsequently, two typical osteosarcoma cell lines, Saos-2 and MG63, were selected to study the changes of cisplatin sensitivity by up-regulating (NICD1 plasmid transfeciton) or decreasing (gamma-secretase complex inhibitor DAPT) the activation state of Notch1 signaling pathway. Our results showed a significant correlation between the expression of Notch1 and cisplatin sensitivity in patient specimens. In vitro, Saos-2 with higher expression of Notch1 had significantly better cisplatin sensitivity than MG63 whose Notch1 level was relatively lower. By targeting regulation in vitro, the cisplatin sensitivity of Saos-2 and MG63 had significantly increased after the activation of Notch1 signaling pathway, and vice versa. Further mechanism investigation revealed that activation/inhibition of Notch1 sensitized/desensitized cisplatin-induced apoptosis, which probably depended on the changes in the activity of Caspase family, including Caspase 3, Caspase 8 and Caspase 9 in these cells. CONCLUSIONS: Our data clearly demonstrated that Notch1 is critical for cisplatin sensitivity in osteosarcoma. It can be used as a molecular marker and regulator for cisplatin sensitivity in osteosarcoma patients.

Results of clubfoot management using the Ponseti method: do the details matter? A systematic review.

BACKGROUND: Although the Ponseti method is accepted as the best choice for treatment of clubfoot, the treatment protocol is labor intensive and requires strict attention to details. Deviations in strict use of this method are likely responsible for the variations among centers in reported success rates. QUESTIONS/PURPOSES: We wished to determine (1) to what degree the Ponseti method was followed in terms of manipulation, casting, and percutaneous Achilles tenotomy, (2) whether there was variation in the bracing type and protocol used for relapse prevention, and (3) if the same criteria were used to diagnose and manage clubfoot relapse. METHODS: We conducted a systematic review of MEDLINE, EMBASE(TM), and the Cochrane Library. Studies were summarized according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses Statement. Five hundred ninety-one records were identified with 409 remaining after deduplication, in which 278 irrelevant studies and 22 review articles were excluded. Of the remaining 109 papers, 19 met our inclusion criteria. All 19 articles were therapeutic studies of the Ponseti method. RESULTS: The details of manipulation, casting, or percutaneous Achilles tenotomy of the Ponseti method were poorly described in 11 studies, whereas the main principles were not followed in three studies. In three studies, the brace type deviated significantly from that recommended, whereas in another three studies the bracing protocol in terms of hours of recommended use was not followed. Furthermore no unified criteria were used for judgment of compliance with brace use. The indication for recognition and management of relapse varied among studies and was different from the original description of the Ponseti method. CONCLUSIONS: We found that the observed clinically important variation may have been the result of deviations from the details regarding manipulation, casting, percutaneous Achilles tenotomy, use of the bar-connected brace, and indication for relapse recognition and management recommended for the classic Ponseti approach to clubfoot management. We strongly recommend that clinicians follow the Ponseti method as it initially was described without deviation to optimize treatment outcomes.

Regulation of prostate cancer cell migration toward bone marrow stromal cell-conditioned medium by Wnt5a signaling.

Bone is a major site of metastasis for several types of malignant tumor. Specific interactions between tumor cells and the bone microenvironment contribute to the tendency of tumors to metastasize to bone. Furthermore, Wnt5a participates in the progression of several types of malignant tumor. This study investigates the role of Wnt5a in the migration of the prostate cancer (PCa) cell line PC3 toward bone marrow stromal cell (BMSC)­conditioned medium (CM). The expression of 22 genes associated with bone metastasis was measured in three PCa cell lines (LNCaP, PC3 and DU145). Subsequently, the proliferation and migration capacities of PC3 cells treated either with small interfering RNA (siRNA) against Wnt5a or with recombinant mouse (rm) Wnt5a were analyzed with alamarBlue and transwell assays. BMSC­CM was collected to evaluate its effect on PC3 cell migration. Also, the expression of Wnt5a in BMSCs was knocked down prior to collection of the CM to evaluate its effects on the migration of PC3 cells. Significantly higher levels of Wnt5a mRNA expression were identified in the PC3 cells, compared with those in LNCaP and DU145 cells. Silencing Wnt5a expression with siRNA reduced the migration capacity of PC3 cells by 50%. The addition of rmWnt5a improved the migration capacity of PC3 cells in a concentration­dependent manner. PC3 cells preferred to migrate toward BMSC­CM than toward the control. CM from Wnt5a siRNA­treated BMSCs significantly reduced PC3 cell migration. Wnt5a promotes PC3 cell migration toward BMSC­CM, indicating that Wnt5a is a potential therapeutic target for the treatment of advanced PCa.

Preoperative aspiration culture for preoperative diagnosis of infection in total hip or knee arthroplasty.

This meta-analysis evaluated preoperative aspiration culture for diagnosing prosthetic joint infection (PJI) in total hip arthroplasty (THA) and total knee arthroplasty (TKA). The pooled sensitivity and specificity were 0.72 (95% confidence interval, 0.65 to 0.78) and 0.95 (0.93 to 0.97), respectively. Subgroup analyses revealed nonsignificant worse diagnostic performance for THA than for TKA (sensitivity, 0.70 versus 0.78; specificity, 0.94 versus 0.96). Preoperative aspiration culture has moderate to high sensitivity and very high specificity for diagnosing PJI.

Poor osteoinductive potential of subcutaneous bone cement-induced membranes for tissue engineered bone.

BACKGROUND: Large segmental bone defects remain a challenge for reconstructive surgeons. A two-stage repair strategy may offer a potential solution. Here, we sought to evaluate the osteoinductive potential of bone cement-induced membranes in an ectopic site. METHODS: First, bone cements were inserted into the subcutaneous tissues of 16 rabbits to induce membrane formation. After 2, 4, 6 and 8 weeks, the induced membranes were harvested to assess their vascularization and osteoinductive potential. Next, bone cements were subcutaneously inserted into 12 rabbits for 4 weeks. These bone cements were then harvested from the newly formed membranes and replaced with granular porous ß-TCP, with or without bone mesenchymal stem cells. New bone formation was then evaluated after 3, 6 and 9 weeks. RESULTS: The highest level of blood vessel formation and bone morphogenetic protein-2 expression in the membranes were found at 4 weeks (p < 0.05). In addition, vascular endothelial growth factor concentration was highest after 2 weeks (p < 0.001), persisting until 8 weeks. However, the results showed little ectopic bone formation at these time points. CONCLUSION: While bone cement-induced membranes appear to provide a suitable environment for bone formation, they fail to drive osteoinduction in non-osseous sites for the purposes of bone tissue engineering.

Magnesium and the risk of cardiovascular events: a meta-analysis of prospective cohort studies.

BACKGROUND: Prospective studies that have examined the association between dietary magnesium intake and serum magnesium concentrations and the risk of cardiovascular disease (CVD) events have reported conflicting findings. We undertook a meta-analysis to evaluate the association between dietary magnesium intake and serum magnesium concentrations and the risk of total CVD events. METHODOLOGY/PRINCIPAL FINDINGS: We performed systematic searches on MEDLINE, EMBASE, and OVID up to February 1, 2012 without limits. Categorical, linear, and nonlinear, dose-response, heterogeneity, publication bias, subgroup, and meta-regression analysis were performed. The analysis included 532,979 participants from 19 studies (11 studies on dietary magnesium intake, 6 studies on serum magnesium concentrations, and 2 studies on both) with 19,926 CVD events. The pooled relative risks of total CVD events for the highest vs. lowest category of dietary magnesium intake and serum magnesium concentrations were 0.85 (95% confidence interval 0.78 to 0.92) and 0.77 (0.66 to 0.87), respectively. In linear dose-response analysis, only serum magnesium concentrations ranging from 1.44 to 1.8 mEq/L were significantly associated with total CVD events risk (0.91, 0.85 to 0.97) per 0.1 mEq/L (P(nonlinearity)= 0.465). However, significant inverse associations emerged in nonlinear models for dietary magnesium intake (P(nonlinearity)= 0.024). The greatest risk reduction occurred when intake increased from 150 to 400 mg/d. There was no evidence of publication bias. CONCLUSIONS/SIGNIFICANCE: There is a statistically significant nonlinear inverse association between dietary magnesium intake and total CVD events risk. Serum magnesium concentrations are linearly and inversely associated with the risk of total CVD events.

The effect of calcium silicate on in vitro physiochemical properties and in vivo osteogenesis, degradability and bioactivity of porous ß-tricalcium phosphate bioceramics.

Porous ß-tricalcium phosphate(TCP)/calcium silicate(CS) composite bioceramics with different weight proportions were prepared to investigate the in vitro effects of CS on the physiochemical properties of TCP and the in vivo effects of CS on the degradability, osteogenesis and bioactivity of TCP. The physiochemical results showed that the addition of CS to porous TCP resulted in a looser and rougher surface and a lower solid density, compressive strength and Young's modulus and a lower pH value as compared to pure CS without any chemical interaction between the TCP and the CS. The in vivo study showed that the material degradation of porous TCP/CS composite bioceramics was slower than that of pure CS, although the osteogenesis, degradability and bioactivity were significantly increased in the long term. Thereafter, the introduction of CS into porous TCP bioceramics is an effective way to prepare bioactive bone grafting scaffolds for clinical use and to control properties such as in vivo degradability and osteoinduction of TCP.

Bone mineral density and all-cause, cardiovascular and stroke mortality: a meta-analysis of prospective cohort studies.

BACKGROUND: Low bone mineral density (BMD) has been associated with increased mortality in prospective cohort studies of the elderly, but the real relationship is still controversial. We undertook a meta-analysis to evaluate the association of BMD with risk of all-cause, cardiovascular and stroke mortality. METHODS: We performed systematic searches on MEDLINE, EMBASE, OVID, CINAHL, and the Cochrane Library. Data extraction was performed independently by two reviewers. For each study, hazard ratios (HRs) and 95% confidence intervals (CI) per standard deviation (SD) decrease in BMD were extracted. Heterogeneity, publication bias, subgroup, and meta-regression analysis were performed. RESULTS: The analysis included 46,182 participants from 10 studies with 3991 all-cause deaths, 1479 cardiovascular deaths and 403 stroke deaths during a median of 7 years follow-up (range 2.8-18.7 years). Lower BMD had a significant inverse relationship with all-cause and cardiovascular mortality, a per SD decrease in BMD at all sites being associated with a 1.17-fold (95% CI: 1.13-1.22) increase in total mortality and a 1.13-fold increase in cardiovascular mortality (95% CI: 1.06-1.20). Lower total hip/femoral neck BMD was also related to all-cause mortality (HR 1.20; 95% CI: 1.09-1.31) and cardiovascular mortality (HR 1.20; 95% CI: 1.04-1.35). BMD was not associated with the risk of stroke mortality (HR 1.08, 95% CI; 0.89-1.28). CONCLUSIONS: Lower BMD is associated with significantly increased risk of all-cause and cardiovascular mortality. There is no significant association between lower BMD and the risk of stroke mortality. The relationship between lower BMD and individual mortality should be investigated further in randomized trials.

Nonlinear association between magnesium intake and the risk of colorectal cancer.

OBJECTIVES: The association between dietary magnesium intake and the risk of colorectal cancer has been examined by many prospective studies, but remains controversial because of inconsistent results. We aimed to carry out a meta-analysis to investigate this. MATERIALS AND METHODS: We assessed this association with categorical and dose-response meta-analysis of data from prospective cohort studies. Relevant studies were identified by searching MEDLINE, EMBASE, and OVID for studies published before 9 June 2012, with no restrictions. Relative risks (RRs) and 95% confidence intervals (CIs) for the highest versus lowest and dose-response association were estimated using random-effects models. Heterogeneity and publication bias was investigated, and subgroup, sensitivity, and meta-regression analyses were carried out. RESULTS: The analysis included 333 510 participants with 7435 colorectal cancers from seven prospective cohort studies. The summary RR for the highest versus the lowest intake of dietary magnesium was 0.81 (95% CI: 0.70-0.92) for colorectal cancer, 0.76 (95% CI: 0.64-0.88) for colon cancer, and 0.82 (95% CI: 0.58-1.06) for rectal cancer. For men and women, the pooled RR was 0.76 (95% CI: 0.51-1.01) and 0.81 (95% CI: 0.68-0.94), respectively. Significant inverse associations of colorectal cancer and dietary magnesium emerged in nonlinear models (p nonlinearity=0.03). The greatest risk reduction was observed when dietary magnesium intake increased from very low levels. CONCLUSION: Dietary magnesium intake has a statistically significant nonlinear inverse association with the risk of colorectal cancer. The greatest reduction for magnesium intake is 200-270 mg/day. Whether the association is causal or because of confounding warrants further investigation.

Soft tissue aneurysmal bone cyst in a 10-year-old girl.

We report the case of a 10-year-old girl with a soft tissue aneurysmal bone cyst (STABC) located in the posterior aspect of the left shoulder. Conventional radiography revealed an oblong mass with a calcified rim. On the computed tomography scan, the lesion appeared to have a non-uniform intralesional density with an incomplete rim. Magnetic resonance imaging revealed a multi-cavity lesion with fluid-fluid levels. Following pathological examination, the lesion was diagnosed as a STABC. This may be only the twentieth reported case in the English literature of this extremely rare benign tumor occurring in soft tissue. Eight months after surgery the patient was assessed at our outpatient clinic and found to have excellent mobility of her left shoulder and no sign of recurrence.

Short-term muscle atrophy caused by botulinum toxin-A local injection impairs fracture healing in the rat femur.

Damaged bone is sensitive to mechanical stimulation throughout the remodeling phase of bone healing. Muscle damage and muscular atrophy associated with open fractures and subsequent fixation are not beneficial to maintaining optimum conditions for mechanical stability. The aim of this study was to investigate whether local muscle atrophy and dysfunction affect fracture healing in a rat femur fracture model. We combined the rat model of a short period atrophy of the quadriceps with femur fracture. Forty-four-month-old male Wistar rats were adopted for this study. Two units of botulinum toxin-A (BXTA) were administered locally into the right side of the quadriceps of each rat, while the same dose of saline was injected into the contralateral quadriceps. After BXTA had been fully absorbed by the quadriceps, osteotomy was performed in both femurs with intramedullary fixation. Gross observation and weighing of muscle tissue, X-ray analysis, callus histology, and bone biomechanical testing were performed at different time points up to 8 weeks post-surgery. Local injection of BXTA led to a significant decrease in the volume and weight of the quadriceps compared to the control side. At the eighth week, the left side femurs of the saline-injected quadriceps almost reached bony union, and fibrous calluses were completely calcified into woven bone. However, a gap was still visible in the BXTA-treated side on X-ray images. As showed by bone histology, there were no mature osseous calluses or woven bone on the BXTA-treated side, but a resorption pattern was evident. Biomechanical testing indicated that the femurs of the BXTA-treated side exhibited inferior mechanical properties compared with the control side. The inferior outcome following BXTA injection, compared with saline injection, in terms of callus resistance may be the consequence of unexpected load and mechanical unsteadiness caused by muscle atrophy and dysfunction.