Engineering Bimetallic Polyphenol for Mild Photothermal Osteosarcoma Therapy and Immune Microenvironment Remodeling by Activating Pyroptosis and cGAS-STING Pathway.

The immunosuppressive tumor microenvironment (ITME) of osteosarcoma (OS) poses a significant obstacle to the efficacy of existing immunotherapies. Despite the attempt of novel immune strategies such as immune checkpoint inhibitors and tumor vaccines, their effectiveness remains suboptimal due to the inherent difficulty in mitigating ITME simultaneously from both the tumor and immune system. The promotion of anti-tumor immunity through the induction of immunogenic cell death and activation of the cGAS-STING pathway has emerged as potential strategies to counter the ITME and stimulate systemic antitumor immune responses. Here, a bimetallic polyphenol-based nanoplatform (Mn/Fe-Gallate nanoparticles coated with tumor cell membranes is presented, MFG@TCM) which combines with mild photothermal therapy (PTT) for reversing ITME via simultaneously inducing pyroptosis in OS cells and activating the cGAS-STING pathway in dendritic cells (DCs). The immunostimulatory pathways, through the syngeneic effect, exerted a substantial positive impact on promoting the secretion of damage-associated molecular patterns (DAMPs) and proinflammatory cytokines, which favors remodeling the immune microenvironment. Consequently, effector T cells led to a notable antitumor immune response, effectively inhibiting the growth of both primary and distant tumors. This study proposes a new method for treating OS using mild PTT and immune mudulation, showing promise in overcoming current treatment limitations.

Custom-made semi-joint prosthesis replacement combined ligament advanced reinforcement system (LARS) ligament reconstruction for the limb salvage surgery of malignant tumors in the distal femur in skeletal immature children.

Purpose: To explore the application of Custom-made Semi-joint prosthesis replacement combined with Ligament Advanced Reinforcement System (LARS) ligament reconstruction for the limb salvage surgery (LSS) of malignant tumors in the distal femur and provide selections for the LSS of malignant tumors in skeletal immature children. Methods: A total of 8 children with malignant tumors in the distal femur who underwent Custom-made Semi-joint prosthesis replacement combined LARS ligament reconstruction for LSS from January, 2018 until December, 2019 in our bone and soft tissue tumor center were retrospectively recruited. The prosthesis related complications, oncological prognosis and knee function were observed, and the surgical efficacy was comprehensively evaluated. Results: The average follow-up time was 36.6 months (30-50 months). The average osteotomy length was 13.2 cm (8-20 cm) according to the preoperative imaging results and the length of the customized prosthesis. Two years after operation, the average MSTS-93 score was 24.4 (16-29) which indicated good limb functions. The range of motion of the knee was 0°-120°, with an maximum average of 100°. At last follow-up, the average height of the children increased by 8.4 cm (6-13 cm), and the average limb shortening was 2.7 cm (1.8-4.6 cm). One patient had wound complications in the early postoperative period, wound scab fell off to form superficial ulcer, in whom debridement and suturing were performed. One patient developed hematogenous disseminated prosthesis infection 2 years after surgery, and the prosthesis is now in situ with anti-infection treatment. One patient developed pulmonary metastasis during follow-up, and received chemotherapy and targeted therapy with lesion well controlled. At the last follow-up, there was no local tumor recurrence or prosthesis loosening. Conclusion: Under the premise of appropriate case selection, customized semi-joint prosthesis replacement combined with LARS ligament reconstruction provides a new option for LSS in children with distal femur malignant tumors. LARS ligament reconstruction ensures the stability and range of motion of the knee joint, which maximally preserves the epiphysis of the tibia side and the growth function of the tibia side, reduces the complications of limb length inequality in the long term and creates conditions for limb lengthening or total joint replacement in adults.

Inhibition of sphingolipid metabolism in osteosarcoma protects against CD151-mediated tumorigenicity.

Osteosarcoma is the most common primary bone tumor, with a poor prognosis owing to the lack of efficient molecular-based targeted therapies. Previous studies have suggested an association between CD151 and distinct consequences in osteosarcoma tumorigenicity. However, the potential of CD151 as a therapeutic target has not yet been sufficiently explored. Here, we performed integrated transcriptomic and metabolomic analyses of osteosarcoma and identified sphingolipid metabolism as the top CD151-regulated pathway. CD151 regulates sphingolipid metabolism primarily through SPTCL1, the first rate-limiting enzyme in sphingolipid biosynthesis. Mechanistically, depletion of CD151 enhanced c-myc polyubiquitination and subsequent degradation. c-myc is vital for the transcriptional activation of SPTLC1. Functionally, sphingolipid synthesis and the SPTLC1 inhibitor, myriocin, significantly suppressed the clonogenic growth of CD151-overexpression cells. Importantly, myriocin selectively restrained CD151-high expression tumor growth in preclinical patient-derived xenograft models. Collectively, these data establish that CD151 is a key mediator of sphingolipid metabolism and provide a new approach to developing novel CD151-based targeted therapies for osteosarcoma.

Feasibility and preliminary efficacy of tantalum components in the management of acetabular reconstruction following periacetabular oncologic resection in primary malignancies.

BACKGROUND: The aim of the study was to investigate the feasibility and preliminary efficacy of tantalum components utility in the reconstruction of acetabular defects following periacetabular oncologic resection of primary malignancies. METHODS: We prospectively collected a consecutive of 15 cases that were treated with tantalum components for acetabular reconstruction after periacetabular oncologic resection from January 2018 to December 2018. The cohort included 8 male and 7 female patients, with a mean age of 47.6 years (range, 33 to 67 years). Pathology types: chondrosarcoma (n = 9), malignant bone giant cell tumor (n = 3) and osteosarcoma (n = 3). Clinical outcomes, functional and radiographic results were recorded in detail for analysis. RESULTS: Patients received planned oncologic resection and tantalum components reconstruction without casualty; they were followed up with a mean of 39.7 months (35-45 months). The mean operation time was 4.0 h (3.0-6.0 h), and the mean blood loss was 1260 ml (800-2200 ml). Functional outcomes were assessed by MSTS-93 scale, with an average of 21.8 (12.0-26.0 scores), among which 3 cases were excellent, 11 were good and 1 was fair. The mean Harris Hip Score was 79.1scores (46.0-92.0 scores) at 1-year follow-up postoperatively. 3(3/15, 20.0%) cases experienced postoperative complications: 2 cases with hip dislocation received closed reduction under general anesthesia and were fixed with hip joint abduction braces for 6 weeks; one case had a superficial infection and received debridement with a delayed wound healing. Oncologic prognosis: one case relapsed at 8-month follow-up and received hemi-pelvic amputation; and another osteosarcoma patient experienced relapse with pulmonary metastasis and received further chemotherapy. No prosthetic loosening, displacement or fracture occurred during the follow-up period. CONCLUSION: Preliminary results suggested that the use of tantalum components in the management of acetabular reconstruction following periacetabular oncologic resection provided reasonable improvement on functional outcomes and early stability of the prostheses. Porous tantalum components are conducive to bony ingrowth, which is a potential alternative to various existing reconstruction techniques to achieve better functional outcomes.

MicroRNA-101a enhances trabecular bone accrual in male mice.

High-throughput microRNA sequencing was performed during differentiation of MC3T3-E1 osteoblasts to develop working hypotheses for specific microRNAs that control osteogenesis. The expression data show that miR-101a, which targets the mRNAs for the epigenetic enzyme Ezh2 and many other proteins, is highly upregulated during osteoblast differentiation and robustly expressed in mouse calvaria. Transient elevation of miR-101a suppresses Ezh2 levels, reduces tri-methylation of lysine 27 in histone 3 (H3K27me3; a heterochromatic mark catalyzed by Ezh2), and accelerates mineralization of MC3T3-E1 osteoblasts. We also examined skeletal phenotypes of an inducible miR-101a transgene under direct control of doxycycline administration. Experimental controls and mir-101a over-expressing mice were exposed to doxycycline in utero and postnatally (up to 8 weeks of age) to maximize penetrance of skeletal phenotypes. Male mice that over-express miR-101a have increased total body weight and longer femora. MicroCT analysis indicate that these mice have increased trabecular bone volume fraction, trabecular number and trabecular thickness with reduced trabecular spacing as compared to controls. Histomorphometric analysis demonstrates a significant reduction in osteoid volume to bone volume and osteoid surface to bone surface. Remarkably, while female mice also exhibit a significant increase in bone length, no significant changes were noted by microCT (trabecular bone parameters) and histomorphometry (osteoid parameters). Hence, miR-101a upregulation during osteoblast maturation and the concomitant reduction in Ezh2 mediated H3K27me3 levels may contribute to the enhanced trabecular bone parameters in male mice. However, the sex-specific effect of miR-101a indicates that more intricate epigenetic mechanisms mediate physiological control of bone formation and homeostasis.

Revision surgeries for tumor endoprostheses around the knee joint: a mid-long-term follow-up of 20 cases.

BACKGROUND: Tumor endoprostheses of the knee joint after limb salvage surgery is associated with high rates of complications, which has introduced great challenges to a delayed revision surgery. The aim of the study was to summarize the failures, functional outcomes and prosthetic survival in revision tumor endoprostheses of the knee joint. METHODS: The clinical data of 20 patients with malignant tumors who received prosthetic revisions after limb salvage surgery from January, 2000 until January, 2018 were retrospectively reviewed. The cohort was constituted of 11 male and 9 female patients with a mean age of 34.1 years (range, 16 to 66 years). Infection cases received two-stage revisions after removing prostheses initially, while all other cases received one-stage revisions. Revision reasons and complications were well documented and analyzed. RESULTS: All patients received complete follow-up with a mean time of 64.7 months (range, 27 to 155 months). A total of 6 (6/20, 30.0%) patients experienced a second complication after revision surgery, of whom, one patient with deep infection experienced repeated infections after prosthetic revision and received amputation surgery; one patient revised of prosthetic fracture experienced an infection and received a second-stage infection revision; one case revised of prosthetic loosening had deep infection receiving anti-infective therapy with prostheses still in position; one case having wound complication healed after receiving two times of debridement surgery; one MBGCT patient experienced a second aseptic loosening 6 years after the initial loosening thus undergoing a second revision; a recurrent osteosarcoma patient died of pulmonary metastasis 3 years after revision surgery. Kaplan-Meier survival curve indicated a 5-year survival rate of initial prostheses was 75%. The Musculoskeletal Tumor Society (MSTS-93) score [20.9 (range, 15 to 27 scores)] at 1 year after revision surgeries was significantly improved (p < 0.001) when compared with the score [17.2 (range, 13 to 21 scores)] before revisions. CONCLUSION: Prosthetic mechanical problems, aseptic loosening and infections were primary reasons for revisions after tumor endoprostheses of the knee joint. Although revision surgeries were complicated while still associated with high risk of failure, which remains the remedy strategy for limb salvage and functional recovery in those patients.

Influence of Patella Position on Soft Tissue Balance and Clinical Outcomes in Patients Undergoing Minimally Invasive Total Knee Arthroplasty, a Randomized Clinical Trial.

BACKGROUND: We hypothesized that subluxating patellar during minimally invasive total knee arthroplasty (MIS-TKA) would affect intraoperative soft tissue balance and postoperative clinical outcome. METHODS: From December 2018 to May 2020, 189 patients receiving primary MIS-TKA were enrolled. The gap-balance technique was used, with patients randomly assigned to undergo osteotomy and balance of soft tissue with patella reduced (group A; n = 93) or subluxated (group B; n = 96). The gap and varus?valgus angle were compared between groups in both extension and flexion position. The gap and varus?valgus angle were also compared before and after reducing patellar in group B. Femoral prosthesis rotation, mechanical femoral axis-to-tibial axis angle, Knee Society Score (KSS), visual analog scale (VAS), and range of motion (ROM) were compared postoperatively between two groups. Follow-up was 12 months. RESULTS: The flexion gap and the varus angle were significantly greater (0.4 mm and 0.7 degree) after patella reduction than before reduction, but the extension joint gap and varus angle were comparable before and after patella reduction. The femoral prosthesis tended to be internally rotated (0.65 degree) in group B. ROM and VAS was better in the group A than in group B at 1 month after surgery, but the differences were not significant at 3, 6 and 12 months. KSS was comparable between the groups after surgery. CONCLUSIONS: During MIS-TKA, as far as possible, soft tissue balance should be achieved with the patella reduced; otherwise, the femoral prosthesis may be installed more internally and, after patella reduction, the flexion gap and varus angle would increase. CLINICAL TRIAL REGISTRATION: Current Controlled Trials ChiCTR2000034106, https://www.chictr.org.cn/hvshowproject.aspx?id=39987.

Surgical Treatment of Sacral Metastatic Tumors.

OBJECTIVE: This study intends to retrospectively analyze the data of patients with sacral metastases in our center, and analyze the treatment methods and therapeutic effects of sacral metastases. METHODS: 73 patients with sacral metastases treated in our hospital from June 2013 to June 2019 were retrospectively analyzed. There were 54 cases of neurological symptoms, 42 cases of sacroiliac joint instability, 24 cases of lower limb muscle weakness and 19 cases of abnormal urination and defecation. Four patients with tumors below S3 underwent complete tumor resection, 23 patients with tumors above S3 and without sacroiliac joint instability underwent tumor curettage and nerve root lysis, 34 patients with tumors above S3 and sacroiliac joint instability underwent tumor curettage, nerve root release and screw rod reconstruction. 12 patients with multiple metastases underwent percutaneous radiofrequency ablation and sacroplasty. VAS was used to evaluate the preoperative and postoperative pain scores, and the postoperative pain relief, neurological function, bowel function, wound healing and complications were evaluated. RESULTS: There were no perioperative death, 8 cases of poor wound healing, 5 cases of nerve injury, postoperative sensory and motor loss of lower limbs. Cerebrospinal fluid (CSF) leak in 7 cases. The patients were followed up for 6-25 months (mean 12 months). The VAS scores of patients with pain symptoms were 7 points before operation and 1.44 points after operation, In 19 patients with abnormal urination and defecation function, 12 patients recovered to normal 3-6 months after operation, 5 cases had no significant change compared with preoperative, and 2 cases had aggravated symptoms; 17 cases of patients with lower limb muscle strength were significantly recovered after operation, and the average muscle strength was increased by 2 grades; 30 cases of patients with unstable sacroiliac joint got internal fixation had significantly pain relief. Pain symptoms of 9 patients were significantly relieved after percutaneous radiofrequency ablation. CONCLUSION: the operation of sacral metastases mainly adopts a relatively conservative surgical method, which can effectively improve the quality of life of patients with sacral metastases by retaining the nerve function and relieving the pain of patients, combining with radiofrequency ablation, sacroplasty and targeted drugs.

Comparison of Percutaneous Transforaminal Endoscopic Discectomy and Microendoscopic Discectomy for the Surgical Management of Symptomatic Lumbar Disc Herniation: A Multicenter Retrospective Cohort Study with a Minimum of 2 Years' Follow-Up.

BACKGROUND: Percutaneous transforaminal endoscopic discectomy (PTED) and microendoscopic discectomy (MED) are alternative minimally invasive procedures for the treatment of symptomatic lumbar disc herniation (LDH). However, insufficient literature exists to highlight the differences between the procedures. OBJECTIVES: This study intended to clarify whether PTED results in better clinical outcomes compared with MED in the surgical management of single-level LDH. STUDY DESIGN: A multicenter retrospective cohort study. SETTING: This study took place in 2 spinal minimally invasive centers in Beijing, China. METHODS: A multicenter retrospective study was conducted in consecutive patients diagnosed with symptomatic LDH receiving PTED or MED in 2 spinal minimally invasive centers from April 2009 to July 2016. A total of 1,053 patients were recruited, of which 632 underwent PTED and 421 underwent MED. All patients were followed with a minimum of 2 years; a set of clinical outcomes were extracted and analyzed. RESULTS: The operation time was similar between groups (71.2 ± 15.1 minutes in the PTED group and 69.4 ± 12.5 minutes in the MED group; P = 0.518); length of incision was significantly shorter; intraoperative blood loss was less in the PTED group (P < 0.001); hospital stay was 3.6 ± 1.5 days in the PTED group and 5.4 ± 2.8 days in the MED group with significant differences detected (P = 0.018); however, intraoperative fluoroscopy was longer with significantly higher cost with the PTED group (P < 0.001). Transient dysesthesia and wound complications were more common in the MED group (P = 0.039 and P = 0.026, respectively); however, no significant differences were found with total complications (P = 0.139). Significant lower Visual Analog Scale pain score (back and leg) were detected on day 1 postoperatively (P = 0.007 and P = 0.018, respectively). No significant differences were found at all other time points (P > 0.05). Significantly better Oswestry Disability Index (ODI) score was detected postoperatively at 1 month in the PTED group (19.6 ± 9.8 vs. 27.2 ± 9.3; P = 0.016); ODI score at other time points did not differ significantly between groups (P > 0.05). Modified MacNab criteria showed that most patients experienced excellent and good results with no significant differences between groups (P = 0.511). LIMITATION: This was a multicenter retrospective study wherein the surgeons may have introduced bias to the study. CONCLUSIONS: Both PTED and MED present to be an acceptable long-term efficacy for the treatment of LDH. Although PTED is associated with longer intraoperative fluoroscopy and a little more cost, it should still be considered superior to MED considering the benefits of lesser invasion, shorter hospital stays, quicker pain relief, and functional recovery.

Inhibition of the epigenetic suppressor EZH2 primes osteogenic differentiation mediated by BMP2.

Bone-stimulatory therapeutics include bone morphogenetic proteins (e.g. BMP2), parathyroid hormone, and antibody-based suppression of WNT antagonists. Inhibition of the epigenetic enzyme enhancer of zeste homolog 2 (EZH2) is both bone anabolic and osteoprotective. EZH2 inhibition stimulates key components of bone-stimulatory signaling pathways, including the BMP2 signaling cascade. Because of high costs and adverse effects associated with BMP2 use, here we investigated whether BMP2 dosing can be reduced by co-treatment with EZH2 inhibitors. Co-administration of BMP2 with the EZH2 inhibitor GSK126 enhanced differentiation of murine (MC3T3) osteoblasts, reflected by increased alkaline phosphatase activity, Alizarin Red staining, and expression of bone-related marker genes (e.g. Bglap and Phospho1). Strikingly, co-treatment with BMP2 (10 ng/ml) and GSK126 (5 µm) was synergistic and was as effective as 50 ng/ml BMP2 at inducing MC3T3 osteoblastogenesis. Similarly, the BMP2-GSK126 co-treatment stimulated osteogenic differentiation of human bone marrow-derived mesenchymal stem/stromal cells, reflected by induction of key osteogenic markers (e.g. Osterix/SP7 and IBSP). A combination of BMP2 (300 ng local) and GSK126 (5 µg local and 5 days of 50 mg/kg systemic) yielded more consistent bone healing than single treatments with either compound in a mouse calvarial critical-sized defect model according to results from µCT, histomorphometry, and surgical grading of qualitative X-rays. We conclude that EZH2 inhibition facilitates BMP2-mediated induction of osteogenic differentiation of progenitor cells and maturation of committed osteoblasts. We propose that epigenetic priming, coupled with bone anabolic agents, enhances osteogenesis and could be leveraged in therapeutic strategies to improve bone mass.

Preoperative low scores of Life Satisfaction Rating predicts poor outcomes after total knee arthroplasty: a prospective observational study.

BACKGROUND: Despite the continued improvement in the surgical techniques during primary total knee arthroplasty (TKA), literatures indicate that up to 10 to 20% patients are not satisfied with their outcomes. Psychological factors in this dissatisfaction are yet to be clearly identified. The aim of this study is to develop a method to assess whether the patient's current mental state is suitable enough to accept a TKA surgery. METHODS: Preoperative demographic and clinical data of 532 patients who underwent TKA were prospectively obtained from January 2012 until December 2016. We recorded the scores evaluated by SF-36 questionnaire and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) preoperatively and 1 year postoperatively. Preoperative Life Satisfaction Rating (LSR) is emphatically evaluated. RESULTS: Poor preoperative score of LSR was a significant predictor of dissatisfaction after TKA. Patients with low LSR reported significant pain and stiffness, although there was no remarkable effect on functionality of the replaced joint. The results also showed that age and BMI were not strong predictors of satisfaction in TKA. CONCLUSION: Our outcomes can help clinicians evaluate whether a patient's current mental status is favorable for TKA. If patients have extreme low scores of LSR (less than 10), a psychological intervention should be recommended for better satisfaction following a TKA surgery. This would also allow surgeons to individually assess the risks and benefits of surgery.

Surgical resection and reconstructive techniques using autologous femoral head bone-grafting in treating partial acetabular defects arising from primary pelvic malignant tumors.

BACKGROUND: The aim of this study is to present and evaluate surgical resection and reconstructive techniques using autologous femoral head bone-grafting in treating partial acetabular defects arising from primary pelvic malignant tumors. METHODS: From January 2009 until January 2015, a total of 20 primary pelvic malignancy cases involving the acetabulum were retrospectively investigated. Surgical resections and reconstructions were conducted based on the type of the tumor with custom osteotomy guides and autologous femoral head bone-grafting. In all cases, prosthesis survival period, complication occurrence, and clinical outcomes data were collected and analyzed. RESULTS: Thirteen male and 7 female patients with an average age of 48 years old (range 23-69 years old) were followed for a median of 69 months (range 48-112 months). Of these cases, 17 included chondrosarcomas and 3 additional patients with a malignant giant cell tumor of bone (MBGCT) as proven by pathology. During follow-up, 3 cases of chondrosarcoma recurred (15%), of which two cases received hemi-pelvic amputation, 1 case of MBGCT relapsed and developed pulmonary metastases. Two cases of acetabular prosthesis with an impending dislocation received closed reduction followed by 6 weeks of hip abduction brace fixation. One case of prosthesis loosening was revised. In another case a deep infection occurred with debridement and prosthesis removal. Musculoskeletal Tumor Society 1993 (MSTS-93) score was utilized to conduct functional evaluation: 13 cases were good, 6 were average and one was poor. CONCLUSION: The precision of the osteotomies performed is likely crucial for this type of reconstructive strategy to be successful. The use of custom guides for acetabular osteotomies and femoral head reconstruction can improve functional outcomes with relatively low complications at the intermediate length of follow-up.

Weight changes after total knee arthroplasty in Chinese patients: a matched cohort study regarding predictors and outcomes.

BACKGROUND: The purpose of this study was to compare 2-year BMI changes between patients undergoing simultaneous bilateral total knee arthroplasty (TKA), staged bilateral TKA, and unilateral TKA. We also sought to determine the predictors of weight change and whether clinically meaningful weight changes affected outcomes. PATIENTS AND METHODS: This retrospective, single-institution study included 202 Chinese patients who received simultaneously bilateral TKA, staged bilateral TKA, or unilateral TKA from 2008 to 2015. There were 49 simultaneous bilateral TKAs, 52 staged bilateral TKAs, and a matched 101 unilateral TKAs. RESULTS: 66.8% (135/202) of patients lost weight after TKA surgery. However, 20.7% (42/202) of patients experienced clinically meaningful weight loss (a BMI decrease of more than 5%). Paired t test showed that 2-year BMI was significantly lower than preoperative BMI (p < 0.001). Weight loss was significantly different between the surgical strategy (p < 0.001). Preoperative BMI and age were predictive of clinically significant weight loss or gain (p < 0.05). Multiple linear regression showed that post-operative weight loss was associated with better Western Ontario and McMaster Universities Osteoarthritis Index and SF-36 scores (p < 0.001). CONCLUSION: Patients after TKA experience weight loss. Age and preoperative BMI predict clinically meaningful weight change. Simultaneous bilateral TKA is associated with higher likelihood of weight loss. Clinically meaningful weight loss experiences better patient-reported outcomes.

Cyclin D1 Gene Silencing Promotes IL-1ß-Induced Apoptosis in Rat Chondrocytes.

This study investigated the effects of cyclin D1 gene silencing on cell proliferation and apoptosis of interleukin-1ß (IL-1ß)-induced osteoarthritis (OA) chondrocytes. Chondrocytes from healthy sprague-dawley rats were divided into blank, OA model (chondrocytes underwent IL-1ß inducement), OA trial (chondrocytes underwent IL-1ß inducement with cyclin D1-shRNA treatment), and negative control (NC; chondrocytes underwent IL-1ß inducement and control-shRNA treatment) groups. Cell proliferation was assessed by CCK-8 assay, and cell cycle and apoptosis by flow cytometry. qRT-PCR and Western blotting were performed to detect cyclin D1 and apoptosis-related factors expression levels. Chondrocyte proliferation increased after 72-96 h after incubation. The OA trial group exhibited reduced cell proliferation at 48, 72, and 96 h after treatment. The OA model, OA trial, and NC groups all contained more cells arrested in G1 phase and had higher apoptosis rates than the blank group. Additionally, the OA trial group contained more cells arrested in G1 phase, with increased apoptosis rates compared to the OA model and NC groups. The OA model group had lowest expression of cyclin D1 whereas the blank group contained the highest among the four groups. qRT-PCR also showed that the OA model, OA trial, and NC groups all had increased expression levels of Bax and reduced expression levels of Bcl-2 and P53 compared to the blank group, whereby by the OA group had the most significant change. The combined evidence in our study shows that cyclin D1 gene silencing suppresses proliferation and induces apoptosis of rat chondrocytes in IL-1ß-induced OA. J. Cell. Biochem. 119: 290-299, 2018. © 2017 Wiley Periodicals, Inc.

Morphologic features of the distal femur and tibia plateau in Southeastern Chinese population: A cross-sectional study.

Morphologic measurements of the femoral and tibial features of western population have been done in several studies, which provides the fundamental data for the design of total knee arthroplasty prosthesis used globally, including China. However, researches on anatomic and morphologic features of the knee in Chinese populations of both sexes have never been conducted. Our study was aimed at investigating the anatomic and morphologic features of the knees of the Southeastern Chinese population by magnetic resonance imaging (MRI) scans, so as to provide parameters for sex- and ethnic-specific implant designs in the future.A total of 245 knees from 244 Chinese adults (130 females and 114 males, aging from 18 to 89 years) who received knee MRI scan from November 2014 to October 2015 were recruited and analyzed. A set of linear and angular parameters, and 6 normalized ratios were measured and calculated on the distal femur and proximal tibia.The knee size was significantly different between sexes. Compared with women, men have larger (P < .01) medial-lateral (ML) and anterior-posterior (AP) dimensions in both distal femur and proximal tibia. Differences in femoral shape, represented by the femur surface ratio, between both sexes were also identified (1.23 ±â€Š0.07 vs 1.27 ±â€Š0.07, P < .01), whereas the ML/AP ratios of the tibia are similar between both sexes (1.44 ±â€Š0.07 vs 1.44 ±â€Š0.09, P = .97). We also found substantial difference in the morphology of femur and tibia plateau in Southeastern Chinese population compared with data obtained from western populations.Our study measured the anatomic and morphologic features of the knees in Southeastern Chinese population, and identified knee morphologic differences between both sexes, as well as western and Chinese population. Further clinical studies are needed to determine other essential parameters for the design of prosthesis to the Chinese populations.

Reduction Osteotomy versus Extensive Release on Clinical Outcome Measures in Simultaneous Bilateral Total Knee Arthroplasty.

BACKGROUND During total knee arthroplasty (TKA) in varus knee deformities, reduction osteotomy (RO) and medial soft tissue release are alternative techniques to aid in achieving deformity correction. In this study, we investigated the effect of RO compared to extensive medial soft tissue release (ER) on clinical outcome measures in simultaneous bilateral TKA. MATERIAL AND METHODS We prospectively enrolled 24 patients (48 knees) with bilateral varus knee deformity from July 2014 to December 20l5. For each patient, one knee was assigned to the RO group and the contralateral knee was assigned to ER group. One year postoperative, follow-up outcomes were collected and analyzed. RESULTS Time to 90° flexion of the knee was significantly different in the RO group (1.6±0.3 days) compared to the ER group (2.0±0.4 days) (p<0.001). Using a 10-item patient reported outcome questionnaire, total scores were significantly different between the RO group (86.3±3.2) and the ER group (82.4±2.7) (p<0.001). Analysis of variance showed a significant difference on the visual analogue scale (VAS) score (p<0.001) but no significant difference in the range of motion (ROM) of the knee (p>0.05) during the follow-up year. CONCLUSIONS Knees treated with RO were associated with greater improvements in pain and function than knees treated with conventional ER technique. Additionally, RO technique did not confer an increased risk for adverse clinical outcomes. RO may therefore by a safe method to decrease postoperative pain, achieve earlier functional recovery, and increase patients' subjective satisfaction after TKA.

Efficacy of a Four-Hour Drainage Clamping Technique in the Reduction of Blood Loss Following Total Hip Arthroplasty: A Prospective Cohort Study.

BACKGROUND During total hip arthroplasty (THA) drainage is used by most surgeons. However, the optimal drainage strategy remains controversial. The aim of this prospective cohort study was to determine the safety and efficacy of a four-hour drainage clamping technique in patients undergoing THA. MATERIAL AND METHODS There were 64 patients who underwent THA from March 2012 to December 2015 who were enrolled in the study; 32 patients were randomly assigned to four hours of a drainage clamping technique (clamping group); 32 patients were treated with a non-clamping drainage technique (non-clamping group). All perioperative clinical details were recorded for comparative analysis. RESULTS The postoperative drainage volume and calculated blood loss were significantly greater in the drainage non-clamping group, p<0.001 and p=0.028, respectively. Significantly more patients in the drainage non-clamping group required a blood transfusion, seven cases versus one case (p=0.023). Significantly more units of blood were transfused in the drainage non-clamping group (p=0.001). No significant differences were found for all other clinical outcome factors. CONCLUSIONS The four-hour drainage clamping technique following THA, compared with drainage non-clamping technique reduced blood loss and requirement for blood transfusion. There was no increase in adverse clinical events using the four-hour drainage clamping method. Therefore, four-hour drainage clamping has the potential for routine use in THA.

A Versatile Protocol for Studying Calvarial Bone Defect Healing in a Mouse Model.

Animal models are vital tools for the preclinical development and testing of therapies aimed at providing solutions for several musculoskeletal disorders. For bone tissue engineering strategies addressing nonunion conditions, rodent models are particularly useful for studying bone healing in a controlled environment. The mouse calvarial defect model permits evaluation of drug, growth factor, or cell transplantation efficacy, together with offering the benefit of utilizing genetic models to study intramembranous bone formation within defect sites. In this study, we describe a detailed methodology for creating calvarial defects in mouse and present our results on bone morphogenetic protein-2-loaded fibrin scaffolds, thus advocating the utility of this functional orthotopic mouse model for the evaluation of therapeutic interventions (such as growth factors or cells) intended for successful bone regeneration therapies.