Proximal versus distal adductor canal blocks for total knee arthroplasty: A protocol for randomized controlled trial.

BACKGROUND: Currently, there remains a paucity of literature about the efficiency of proximal adductor canal block (PACB) versus distal adductor canal block (DACB) for pain management after total knee arthroplasty (TKA). The purpose of this study is to perform a randomized controlled trial to compare the efficiency of PACB versus DACB for early postoperative pain treatment after TKA. METHODS: This study is a 2-arm, parallel-group, randomized controlled trial that is conducted at a single university hospital in China. Subjects presenting for unilateral TKA are randomized in a 1:1 ratio to either a PACB or DACB group. The primary outcome of this noninferiority study is opioid consumption within the first 24 hours following surgery. Secondary outcomes include quadriceps strength, pain scores, distance ambulated, and patient satisfaction. Continuous variables are compared using Student t test. RESULTS: This clinical trial is expected to provide evidence of whether the PACB and DACB provide similar analgesia after TKA. TRIAL REGISTRATION: This study protocol was registered in Research Registry (researchregistry5440).

Exosomes in osteoarthritis and cartilage injury: advanced development and potential therapeutic strategies.

Articular cartilage injury is a common clinical problem, which can lead to joint dysfunction, significant pain, and secondary osteoarthritis (OA) in which major surgical procedures are mandatory for treatment. Exosomes, as endosome-derived membrane-bound vesicles, participating in intercellular communications in both physiological and pathophysiological conditions, have been attached great importance in many fields. Recently, the significance of exosomes in the development of OA has been gradually concerned, while the therapeutic value of exosomes in cartilage repair and OA treatment has also been gradually revealed. The functional difference of different types and derivations of exosomes are determined by their specific contents. Herein, we provide comprehensive understanding on exosome and OA, including how exosomes participating in OA, the therapeutic value of exosomes for cartilage injury/OA, and related bioengineering strategies for future therapeutic design.

The dual character of exosomes in osteoarthritis: Antagonists and therapeutic agents.

Exosomes have gained increasing attention as they participate in cell cross-talk in pathological environments and are functional paracrine factors of therapeutic stem cells. Osteoarthritis (OA) is a common age-related degenerative joint disease, leading to a debilitating lifestyle for sufferers. However, currently no drugs on the market promote cartilage repair, and the patients usually have to undergo arthroplasty in the late stage of OA. Although significant progress has been made in the development of stem cells for the treatment of OA and cartilage injury, problems like immune rejection remain. Recently, increasing evidence has demonstrated that exosomes from the joint microenvironment ("negative" exosomes) could play vital and complicated roles in the progression of OA. Moreover, exosomes from therapeutic cells ("therapeutic" exosomes) have also shown enormous potential for OA therapy/cartilage repair. Here, we first discuss the definition and biological background of exosomes. Then, we critically examine the roles of the "negative" exosomes in OA-affected joint. Then, we will cover the potential of the "therapeutic" exosomes for OA therapy/cartilage repair. Next, the recent progress of tissue engineering with exosomes, especially for OA therapy/cartilage repair, will also be discussed. Finally, the limitations and opportunities of exosome-based OA therapy will be outlined. STATEMENT OF SIGNIFICANCE: As natural extracellular vesicles, exosomes participate in the intercellular communication. On the basis of biological characteristics of exosomes, exosomes have their two sides for osteoarthritis (OA). On the one hand, exosomes in the OA microenvironment are involved in pathology of OA. On the other hand, exosomes from therapeutic cells have the potential as advanced strategies for OA therapy. In addition, the development of tissue engineering technology is beneficial to the exosome-based OA therapy. According to the latest research status, exosomes are of great significance and interest for the personalized and precision treatment of OA in the future, despite the limitations and challenges.

Monocyte chemoattractant protein­1 promotes the proliferation, migration and differentiation potential of fibroblast­like synoviocytes via the PI3K/P38 cellular signaling pathway.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints and joint destruction. Monocyte chemoattractant protein 1 (MCP­1) is highly expressed in the joints of patients suffering from RA. The present study aimed to evaluate the effects of MCP­1 on the phenotype of fibroblast­like synoviocytes (FLSs) and their differentiation potential towards vascular endothelial cells. The expression of MCP­1 in collagen­induced arthritis (CIA) rats was investigated by PCR, ELISA and immunohistology. Cell proliferation induced by MCP­1 was measured using a Cell Counting Kit­8 (CCK­8) and 5­Bromo­2­deoxyuridine ELISA assay. In addition, the effects of MCP­1 on the migration of FLSs was examined using a Transwell assay. Activation of PI3K and P38 were investigated by western blotting following MCP­1 treatment. The vascular endothelial cell markers, tumor necrosis factor alpha (TNF­α) and interleukin­1 beta (IL­ß), were also examined by western blotting. LY294002 [PI3K inhibitor, (LY)] and SB203580 [P38 inhibitor, (SB)] were used to examine the proliferative and pro­differentiation effect of PI3K and P38. The present findings showed that the expression level of MCP­1 in the synovium of CIA rats was significantly higher compared with controls. The present in vitro study suggested that MCP­1 increased the FLSs cell numbers with a maximal effect at 200 ng/ml, and induced the maximal phosphorylation of PI3K at 15 min and P38 at 30 min. In addition, MCP­1 stimulation significantly increased the migration of FLSs. Furthermore, MCP­1­induced the expression of vascular endothelial growth factor and CD31 in FLSs. Suppression of PI3K and P38 was found to reduce MCP­1 induced FLSs proliferation and migration, and decreased the expression levels of angiogenesis markers increased following MCP­1 treatment. MCP­1 was also found to increase the expression levels of both TNF­α and IL­ß. Therefore, MCP­1 could promote the proliferation and migration of FLSs, and was found to increase the expression levels of various angiogenesis markers via PI3K/P38, suggesting a role for this pathway in synovium hyperplasia in RA.

En Bloc lumpectomy of T12 vertebra for progressive hepatocellular carcinoma metastases following liver transplantation: A case report.

RATIONALE: Liver transplantation (LT) is the preferred surgical option for the treatment of early hepatocellular carcinoma (HCC). In contrast, surgical treatment of progressive HCC metastasized to the spine following LT constitutes a considerable challenge. Here, we report the first case of progressive HCC metastasized to the T12 vertebra after local radiotherapy, treated successfully with en bloc lumpectomy following LT for HCC. PATIENT CONCERNS: A 40-year-old man who had undergone LT for the treatment of HCC 2 months prior presented to our clinic with symptoms of progressive back pain. Magnetic resonance imagining (MRI) and positron emission tomography (PET) examinations showed a solitary metastasis at T12 without recurrence in the liver or metastasis to other organs. DIAGNOSES: The patient was diagnosed with HCC metastasized to the T12 vertebra after liver transplantation. INTERVENTIONS: Local radiation therapy of the T12 vertebra was performed; however, the lesion continued to grow one month after irradiation. Accordingly, the patient was treated with en bloc lumpectomy of the T12 vertebra. After surgery, the patient reported significant pain relief. At 11 months post-surgery, a C4 metastasis with spinal cord compression was revealed by MRI. Multiple grafted liver metastases were also detected by ultrasound along with several lung metastases, which were discovered by X-ray. The patient was treated with a pedicle screw system and a mesh cage filled with frozen autografts for C4 metastasis. OUTCOMES: The patient died 15 months after liver transplantation due to recurrence in the liver and metastasis to the lung. LESSONS: En bloc lumpectomy may be a viable therapeutic option for patients with progressive solitary spinal metastases after LT refractory to radiotherapy. Use of immunosuppressive therapy after LT may significantly inhibit immune function, making patients more susceptible to HCC recurrence and bone metastasis.

Surgical treatment of progressive cauda equina compression caused by spontaneous spinal subdural hematoma: A case report.

RATIONALE: Spontaneous spinal subdural hematoma (SSDH) without an underlying pathology is a very rare condition. The treatment protocol for SSDH is early diagnosis and treatment before irreversible damage to neural tissue. However, there is no agreement on the etiopathogenesis, as well as the need for surgery to treat spontaneous SSDH. Here, we report a rare case of spontaneous SSDH with progressive deterioration and symptoms of cauda equina syndrome after ineffective conservative treatment. PATIENT'S CONCERN: A 38-year-old male patient presented with sudden lower back and bilateral leg pain. DIAGNOSIS: A magnetic resonance imaging (MRI) scan on the third day after the onset of symptoms revealed a subdural hematoma from L1 to S1, presenting as hyperintensities on T1 weighted sequences and hypointensities to isointensities on T2 weighted sequences. INTERVENTION: Laminectomy and subdural evacuation were performed immediately. OUTCOMES: An abnormal ligamentum flavum was observed intraoperatively. A histological examination revealed extravasation of blood in the degenerated ligamentum flavum. Postoperatively, the lower limb pain improved immediately. At the 6-month follow-up, the pain and numbness of the lower limb disappeared, and the muscle strength of both legs recovered completely with normal gait. LESSONS: Spontaneous SSDH with ligamentum flavum hematoma was caused by a sudden increase of intravenous pressure, resulting from a marked surge in the intra-abdominal or intrathoracic pressure. Consecutive MRI scans provided valuable information, leading to a diagnosis of spontaneous SSDH. The treatment protocol for spontaneous SSDH should be determined based on the location and stage of the hematoma, as well as the subject's neurological status.

Correlation between three-dimensional medial longitudinal arch joint complex mobility and medial arch angle in stage II posterior tibial tendon dysfunction.

BACKGROUND: The purpose of this study was to evaluate correlation between three-dimensional medial longitudinal arch joint complex mobility and medial arch angle in stage II posterior tibial tendon dysfunction flatfoot under loading. METHODS: CT scans of 15 healthy feet and 15 feet with stage II posterior tibial tendon dysfunction flatfoot were taken both in non- and simulated weight-bearing condition. The CT images of the hindfoot and medial longitudinal arch bones were reconstructed into three-dimensional models with Mimics and Geomagic reverse engineering software. The three-dimensional complex mobility of each joint in the medial longitudinal arch and their correlation with the medial arch angle change were calculated. RESULTS: From non- to simulated weight-bearing condition, the medial arch angle change and the medial longitudinal arch joints mobility were significant larger in stage II posterior tibial tendon dysfunction flatfoot (p<0.05). The eversion of the talocalcaneal joint, the proximal translation of the calcaneus relative to the talus, the dorsiflexion of the talonavicular joint, the dorsiflexion and abduction of the medial cuneonavicular joint, and the lateral translation of the medial cuneiform relative to the navicular, and the dorsiflexion of the first tarsometatarsal joint were all significantly correlated to the medial arch angle change in stage II posterior tibial tendon dysfunction flatfoot (all r>0.5, p<0.05). CONCLUSIONS: There is increased mobility in the medial longitudinal arch joints in stage II posterior tibial tendon dysfunction flatfoot and the medial arch angle change under loading causes displacement not only at hindfoot joints but also involve midfoot and forefoot joint.

P65-mediated miR-590 inhibition modulates the chemoresistance of osteosarcoma to doxorubicin through targeting wild-type p53-induced phosphatase 1.

Osteosarcoma (OS) is a primary malignant bone tumor with high morbidity. Developing new therapeutic approaches with neoadjuvant is of great interest in OS treatment. Reportedly, ataxia telangiectasia mutated (ATM)/ataxia telangiectasia and radiation resistance gene 3 related (ATR)-p53 signaling is considered as a critical DNA damage signaling pathway sensitizing cancer cells to chemotherapies; while wild-type p53-induced phosphatase 1 (WIP1), an oncogene overexpressed in diverse cancers, has been regarded as a critical inhibitor in the ATM/ATR-p53 DNA damage signaling pathway. Herein, the expression of WIP1 in OS tissues and cell lines was examined; to investigate the mechanism of WIP1 abnormal upregulation, online tools were used to predict the upstream regulatory microRNAs (miRNAs) targeting WIP1. Among the candidate miRNAs, the expression and detailed function of miR-590 were validated. Through binding to the 3'-untranslated region of WIP1, miR-590 inhibited WIP1 expression and, therefore, enhanced the effect of Dox on OS cell proliferation and apoptosis through downstream ATM-p53 signaling. Moreover, RELA could bind to the promoter region of miR-590 to inhibit its expression, thereby affecting downstream WIP1 and ATM-p53 signaling. The expression of p65 was upregulated in OS tissues, indicating that the effect of p65 inhibition on cell viability, apoptosis, and related mechanisms could be partially restored by miR-590 inhibition. Taken together, these results showed that p65-mediated miR-590/WIP1/ATM-p53 modulation might be a novel target to enhance the cellular effect of Dox on OS cell lines.

Autograft or Allograft? Irradiated or Not? A Contrast Between Autograft and Allograft in Anterior Cruciate Ligament Reconstruction: A Meta-analysis.

PURPOSE: To compare the clinical outcomes and adverse events associated with irradiated and nonirradiated allografts in anterior cruciate ligament (ACL) reconstruction. METHODS: PubMed, Web of Science, and EMBASE were searched for randomized controlled trials from January 1990 to March 2018 to compare autograft with allograft in ACL reconstruction. Both objective and subjective outcomes of the function and adverse events were meta-analyzed. Two comparisons were summarized: (1) autograft and nonirradiated allograft and (2) autograft and irradiated allograft. The bias risk was based on the Cochrane Handbook for Systematic Reviews of Interventions. The overall risk ratio or weighted mean difference was calculated using a fixed- or random-effects model. Heterogeneity between studies was evaluated by the Q and the I2 statistics. RESULTS: Eleven trials were included in this review for meta-analysis. A total of 1,172 patients were involved (465 autograft and 461 nonirradiated allograft; 141 autograft and 138 irradiated allograft patients). The average follow-up varied from 2 to >10 years. The mean patient age varied from 22 to 32.8 years. The total failure rate was 2.5%. Our analyses demonstrated better clinical outcomes in autograft than irradiated allograft, which could be observed clearly through the International Knee Documentation Committee score (3.84; 95% confidence interval [CI], 1.93-5.76; P < .0001; I2 = 0%), Lysholm score (2.94; 95% CI, 0.66-5.22; P = .01; I2 = 0%), and Tegner score (0.14; 95% CI, -0.08 to 0.36; P = .22; I2 = 0%) with fewer adverse events 0.20 (95% CI, 0.11-0.39; P < .00001; I2 = 0%). There were no significant differences in autograft and nonirradiated allograft groups (P = .47, P = .27, P = .24, and P = .24, respectively). CONCLUSIONS: Autograft offered greater advantages in functional outcomes and adverse events than irradiated allograft in ACL reconstruction; however, there were no significant differences between autograft and nonirradiated allograft in ACL reconstruction. LEVEL OF EVIDENCE: Level II, meta-analysis of Level I and Level II studies.

Modic Changes in the Lumbar Spine are Common Aging-related Degenerative Findings that Parallel With Disk Degeneration.

STUDY DESIGN: This is a cross-sectional study. OBJECTIVE: To determine the prevalence and distribution patterns of Modic changes (MCs) in the lumbar spine and their associations with disk degeneration in mainland Chinese using a sample of general population. SUMMARY OF BACKGROUND DATA: Previous studies reported that the prevalence of MCs in Hong Kong Chinese was much lower than in other populations. Moreover, their associations with disk degeneration need further study. MATERIALS AND METHODS: The study sample consisted of 442 subjects (53.6±14.9 y; range, 20-88 y) randomly selected from a typical Chinese community. Lumbar spines were imaged using a 3.0 T magnetic resonance scanner. Eleven endplates (L1-S1) in the lumbar spine were evaluated for the presence of MCs, type, location, and size to determine MCs prevalence and distribution patterns. Disk degeneration was graded using a Pfirrmann scale. RESULTS: MCs were present in 209 (47.3%) subjects and 593 (12.2%) endplates. Among these endplates, 84.1% (499) were type II, 9.1% (54) were type I, and 6.4% (38) were mixed MCs. Approximately 2/3 MCs were present in the lower lumbar spine and 44.9% of MCs were at the L5/S1 disk level. Most MCs (73.9%) involved both endplates of a disk. Greater age [odds ratio (OR)=2.44 for each 10-year increase, P<0.001] and body mass index (OR=1.07, P=0.016) were associated with the presence of MCs, as was adjacent disk degeneration (OR=6.00, P<0.001), controlling for age and other covariates. Greater age, body mass index, and adjacent disk degeneration were also associated with greater MCs size. CONCLUSIONS: MCs are common in mainland Chinese, with type II predominating. MCs mainly present in the lower lumbar region and tend to occur in pairs. MCs were strongly associated with age and disk degeneration, suggesting MCs may be aging-related degenerative findings that parallel disk degeneration. LEVEL OF EVIDENCE: Level II.

Injection of synthetic mesenchymal stem cell mitigates osteoporosis in rats after ovariectomy.

Osteoporosis is a severe skeletal disorder. Patients have a low bone mineral density and bone structural deterioration. Mounting lines of evidence suggest that inappropriate apoptosis of osteoblasts/osteocytes leads to maladaptive bone remodelling in osteoporosis. It has been suggested that transplantation of stem cells, including mesenchymal stem cells, may alter the trajectory of bone remoulding and mitigate osteoporosis in animal models. However, stem cells needed to be carefully stored and characterized before usage. In addition, there is great batch-to-batch variation in stem cell production. Here, we fabricated therapeutic polymer microparticles from the secretome and membranes of mesenchymal stem cells (MSCs). These synthetic MSCs contain growth factors secreted by MSCs. In addition, these particles display MSC surface molecules. In vitro, co-culture with synthetic MSCs increases the viability of osteoblast cells. In a rat model of ovariectomy-induced osteoporosis, injection of synthetic MSCs mitigated osteoporosis by reducing cell apoptosis and systemic inflammation, but increasing osteoblast numbers. Synthetic MSC offers a promising therapy to manage osteoporosis.

The Effect of Cartilage Fragments on Femoral Tunnel Widening After Anterior Cruciate Ligament Reconstruction: A Prospective Randomized Controlled Study.

PURPOSE: To analyze the effect of cartilage fragments on tunnel widening and tendon-bone integration at 2 years' follow-up after anterior cruciate ligament reconstruction (ACLR). METHODS: A prospective randomized controlled study was performed in 116 patients who underwent ACLR with autologous hamstring tendons augmented with cartilage fragments (study group, n = 56) or without any augmentation (control group, n = 60). All patients were followed up for 25.6 months (range, 24-28 months), and the International Knee Documentation Committee score, Lysholm score, and visual analog scale score were determined. Computed tomography scans of all patients were obtained 2 years after surgery to evaluate the diameter of the femoral tunnel and thereby assess the amount of tunnel widening. Magnetic resonance imaging evaluation was performed 2 years postoperatively to evaluate the status of the graft in the femoral tunnel. In addition, 5 patients underwent biopsy of the tendon-bone interface at 24 months postoperatively with histologic assessment and transmission electron microscopy. RESULTS: A total of 107 patients completed the follow-up. There were no significant differences between the 2 groups in terms of International Knee Documentation Committee score (P = .07), Lysholm score (P = .10), and visual analog scale score (P = .57) at 24 months' follow-up. The femoral tunnel diameter and the tunnel widening percentage in the study group were significantly smaller than those in the control group (P < .001). The signal-noise quotient value of the graft in the femoral tunnel was 10.4 ± 7.0 in the study group, which was significantly lower than that in the control group (19.5 ± 9.2, P < .001). Histologic studies of the tendon-bone interface showed that there were more bone formations containing chondroid cells with aligned connective tissue in the study group compared with the control group; in addition, the diameter of the collagen fibrils in the study group was considerably thicker than that in the control group (P < .05). CONCLUSIONS: The use of cartilage fragments was effective in preventing femoral tunnel widening and seemed to promote the tendon-bone integration process after ACLR. LEVEL OF EVIDENCE: Level II, prospective randomized controlled study.

Arthroscopic Rotator Cuff Repair With Graft Augmentation of 3-Dimensional Biological Collagen for Moderate to Large Tears: A Randomized Controlled Study.

BACKGROUND: Due to the highly organized tissue and avascular nature of the rotator cuff, rotator cuff tears have limited ability to heal after the tendon is reinserted directly on the greater tubercle of the humerus. Consequently, retears are among the most common complications after rotator cuff repair. Augmentation of rotator cuff repairs with patches has been an active area of research in recent years to reduce retear rate. HYPOTHESIS: Graft augmentation with 3D collagen could prevent retears of the repaired tendon and improve tendon-bone healing in moderate to large rotator cuff tears. STUDY DESIGN: Randomized controlled study; Level of evidence, 2. METHODS: A prospective, randomized controlled study was performed in a consecutive series of 112 patients age 50 to 85 years who underwent rotator cuff repair with the suture-bridge technique (58 patients, control group) or the suture-bridge technique augmented with 3-dimensional (3D) collagen (54 patients, study group). All patients were followed for 28.2 months (range, 24-36 months). Visual analog scale score for pain, University of California Los Angeles (UCLA) shoulder score, and Constant score were determined. Magnetic resonance imaging was performed pre- and postoperatively (at a minimum of 24 months) to evaluate the integrity of the rotator cuff and the retear rate of the repaired tendon. Three patients in each group had biopsies at nearly 24 months after surgery with histological assessment and transmission electron microscopy. RESULTS: A total of 104 patients completed the final follow-up. At the 12-month follow-up, the UCLA shoulder score was 28.1 ± 1.9 in the study group, which was significantly better than that in the control group (26.9 ± 2.1, P = .002). The Constant score was also significantly better in the study group (87.1 ± 3.2) than in the control group (84.9 ± 4.2, P = .003). However, at the final follow-up, no significant differences were found in the UCLA shoulder scores (29.4 ± 1.9 in the control group and 30.0 ± 1.6 in the study group, P = .052) or Constant scores (89.9 ± 3.2 in the control group and 90.8 ± 3.5 in the study group, P = .18). In terms of structural integrity, more patients in the study group had a favorable type I retear grade (18/51) than in the control group (10/53) ( P = .06). The postoperative retear rate was 34.0% in the control group and 13.7% in the study group, thus indicating a significantly lower retear rate in the study group ( P = .02). Biopsy specimens of the tendon-bone interface in 6 patients revealed more bone formation and more aligned fibers with larger diameters in the study group than in the control group. No intraoperative or postoperative complications were noted in either group. CONCLUSION: 3D collagen augmentation could provide effective treatment of moderate to large rotator cuff tears, providing substantial functional improvement, and could reduce the retear rate. This technique could also promote new tendon-bone formation, thus exerting a prominent effect on tendon-bone healing.

Augmented Versus Nonaugmented Repair of Acute Achilles Tendon Rupture: A Systematic Review and Meta-analysis.

BACKGROUND: Although simple end-to-end repair of the Achilles tendon is common, many augmented repair protocols have been implemented for acute Achilles tendon rupture. However, whether augmented repair is better than nonaugmented repair of an acute Achilles tendon rupture is still unknown. PURPOSE: To conduct a meta-analysis to determine whether augmented surgical repair of an acute Achilles tendon rupture improved subjective patient satisfaction without an increase in rerupture rates. Secondary outcomes assessed included infections, ankle range of motion, calf muscle strength, and minor complications. STUDY DESIGN: Meta-analysis. METHODS: A systematic literature search of peer-reviewed articles was conducted to identify all randomized controlled trials (RCTs) comparing augmented repair and nonaugmented repair for acute Achilles tendon rupture from January 1980 to August 2016 in the electronic databases of PubMed, Web of Science (SCI-E/SSCI/A&HCI), and EMBASE. The keywords (Achilles tendon rupture) AND (surg* OR operat* OR repair* OR augment* OR non-augment* OR end-to-end OR sutur*) were combined, and results were limited to human RCTs and controlled clinical trials published in the English language. Four RCTs involving 169 participants were eligible for inclusion; 83 participants were treated with augmented repair and 86 were treated with nonaugmented repair. RESULTS: Augmented repair led to similar responses when compared with nonaugmented repair for acute Achilles tendon rupture (93% vs 90%, respectively; P = .53). The rerupture rates showed no significant difference for augmented versus nonaugmented repair (7.2% vs 9.3%, respectively; P = .69). No differences in superficial and deep infections occurred in augmented (7 infections) and nonaugmented (8 infections) repair groups during postoperative follow-up ( P = .89). The average incisional infection rate was 8.4% with augmented repair and 9.3% with nonaugmented repair. No significant differences in other complications were found between augmented (7.2%) and nonaugmented (8.1%) repair ( P = .80). CONCLUSION: Augmented repair, when compared with nonaugmented repair, was not found to improve patient satisfaction or reduce rerupture rate or infection rate. These conclusions are based on 4 trials with small sample sizes, and larger randomized trials are required to confirm these results.

MicroRNA-124a inhibits cell proliferation and migration in liver cancer by regulating interleukin-11.

Liver cancer is the sixth most common malignant tumour and ranks in the top three cancers with regard to mortality due to metastasis and postsurgical recurrence. It is significant to understand the mechanisms underlying liver cancer for diagnosis and treatment. Cumulative evidence suggests that the abnormal regulation of microRNAs (miRNAs/miRs) may contribute to the development and metastasis of cancer. miR­124a acts as a tumour suppressor in osteosarcoma, endometrial carcinoma, prostate cancer, and glioblastoma. However, the effects of miR­124a in liver cancer and its biological mechanism are not fully understood. It has been demonstrated that miR­124a is downregulated and interleukin (IL)­11 is upregulated in the liver cancer tissues. In the present study, miR­124a upregulation inhibited cell proliferation, migration and promoted cell apoptosis. Through a dual­luciferase reporter assay, it was verified that IL­11 is a direct target of miR­124a. Furthermore, the overexpression of miR­124a repressed the secretion of IL­11 from hepatoma cells. Finally, it was identified that mimics of miR­124a increased the expression of tissue inhibitor of matrix metalloproteinase­2 (TIMP­2) and Caspase­3 and decreased the expression levels of matrix metalloproteinase 2 (MMP2), MMP9, B­cell lymphoma 2, signal transducer and activator of transcription 3 (STAT3), and phosphorylated­STAT3. In conclusion, the results indicated that miR­124a has an important role as a tumour suppressor gene by targeting IL­11. These findings may provide novel insights for clinical treatments to prevent the development of liver cancer.

Bone metastases from hepatocellular carcinoma: clinical features and prognostic factors.

BACKGROUND: Bone metastases (BMs) from hepatocellular carcinoma (HCC) is an increasingly common disease in Asia. We assessed the clinical features, prognostic factors, and differences in outcomes related to BMs among patients with different treatments for HCC. METHODS: Forty-three consecutive patients who were diagnosed with BMs from HCC between January 2010 and December 2014 were retrospectively enrolled. The clinical features were identified, the impacts of prognostic factors on survival were statistically analyzed, and clinical data were compared. RESULTS: The median patient age was 54 years; 38 patients were male and 5 female. The most common site for BMs was the trunk (69.3%). BMs with extension to the soft tissue were found in 14 patients (32.5%). Most (90.7%) of the lesions were mixed osteolytic and osteoblastic, and most (69.8%) patients presented with multiple BMs. The median survival after BMs diagnosis was 11 months. In multivariate analyses, survival after BM diagnosis was correlated with Karnofsky performance status (P=0.008) and the Child-Pugh classification (P<0.001); BM-free survival was correlated with progression beyond the University of California San Francisco criteria (P<0.001) and treatment of primary tumors (P<0.001). BMs with extension to soft tissue were less common in liver transplantation patients. During metastasis, the control of intrahepatic tumors was improved in liver transplantation and hepatectomy patients, compared to conservatively treated patients. CONCLUSIONS: The independent prognostic factors of survival after diagnosis of BMs were the Karnofsky performance status and Child-Pugh classification. HCC patients developed BMs may also benefit from liver transplantation or hepatectomy.

Osteosarcoma cell-intrinsic colony stimulating factor-1 receptor functions to promote tumor cell metastasis through JAG1 signaling.

Therapeutic antibodies or inhibitors targeting CSF-1R block colony stimulating factor-1/colony stimulating factor-1 receptor (CSF-1/CSF-R) signaling, and have shown remarkable efficacy in the treatment of cancer. However, little is known about tumor cell-intrinsic CSF-1R effects. Here, we show that human osteosarcomas contain CSF-1R-expressing cancer subpopulations, and demonstrate that osteosarcoma cell-intrinsic CSF-1R promotes growth in vitro and in vivo. CSF-1R inhibition in osteosarcoma cells by RNA interference suppresses cell proliferation and tumor growth in mice. Conversely, CSF-1R overexpression enhances cell proliferation and accelerates tumor growth. CSF-1R overexpression can significantly enhance osteosarcoma cell migration, invasion, and epithelial-mesenchymal transition (EMT), whereas silencing CSF-1R inhibits these processes. Microarray analysis suggests that jagged 1 (JAG1) can function as a downstream mediator of CSF-1R. Moreover, we report a signaling pathway involving CSF-1R and JAG1 that sustains osteosarcoma cell migration and invasion. Our results identify osteosarcoma cell intrinsic functions of the CSF-1R/JAG1 axis in dissemination of osteosarcoma cells.

Adipose-Derived Stem Cells Suppress Inflammation Induced by IL-1ß through Down-Regulation of P2X7R Mediated by miR-373 in Chondrocytes of Osteoarthritis.

Adipose-derived stem cells (ADSCs) were previously considered to have an anti-inflammatory effect, and Interleukin-1ß (IL-1ß) was found to be a pro-inflammatory factor in chondrocytes, but the mechanism underlying ADSCs and IL-1ß is unclear. In this study, we investigate whether P2X7 receptor (P2X7R) signalling, regulated by microRNA 373 (miR-373), was involved in the ADSCs and IL-1ß mediated inflammation in osteoarthritis (OA). Chondrocytes were collected from 20 OA patients and 20 control participants, and ADSCs were collected from patients who had undergone abdominal surgery. The typical surface molecules of ASDCs were detected by flow cytometry. The level of nitric oxide (NO) was determined by Griess reagent. Concentrations of prostaglandin E2 (PGE2), interleukin 6 (IL-6), matrix metallopeptidase 3 (MMP-3) were detected by enzyme-linked immunosorbent assay (ELISA). The expressions of IL-6, MMP-3, miR-373 and P2X7R were determined by real-time polymerase chain reaction (PCR), and Western blot was used to detect the protein expression of P2X7R. The typical potential characters of ADSCs were verified. In chondrocytes or OA tissues, the miR-373 expression level was decreased, but the P2X7R expression was increased. IL-1ß stimulation increased the level of inflammatory factors in OA chondrocytes, and ADSCs co-cultured with IL-1ß-stimulated chondrocytes decreased the inflammation. OA chondrocytes transfected with the miR-373 inhibitor increased the inflammation level. The miR-373 mimic suppressed the inflammation by targeting P2X7R and regulated its expression, while its effect was reversed by overexpression of P2X7R. IL-1ß induced inflammation in OA chondrocytes, while ADSCs seemed to inhibit the expression of P2X7R that was regulated by miR-373 and involved in the anti-inflammatory process in OA.

Treatment of Crowe Type-IV Hip Dysplasia Using Cementless Total Hip Arthroplasty and Double Chevron Subtrochanteric Shortening Osteotomy: A 5- to 10-Year Follow-Up Study.

BACKGROUND: The purpose of this study was to evaluate the functional and radiographic results of patients with Crowe type-IV hip dysplasia treated by cementless total hip arthroplasty and double chevron subtrochanteric osteotomy. METHODS: From January 2000 to February 2006, cementless total hip arthroplasty with a double chevron subtrochanteric shortening osteotomy was performed on 18 patients (22 hips) with Crowe type-IV dysplasia. The acetabular cup was placed in the position of the anatomic hip center, and subtrochanteric femoral shortening osteotomy was performed with the use of a double chevron design. The clinical and radiographic outcomes were reviewed with a mean follow-up of 6.5 years (5-10 years). RESULTS: The mean amount of femoral subtrochanteric shortening was 38 mm (25-60 mm). All osteotomy sites were healed by 3-6 months without complications. The mean Harris Hip Score improved significantly from 47 points (35-65 points) preoperatively to 88 points (75-97 points) at the final follow-up. The Trendelenburg sign was corrected from a positive preoperative status to a negative postoperative status in 12 of 22 hips. No acetabular and femoral components have loosened or required revision during the period of follow-up. CONCLUSION: Cementless total hip arthroplasty using double chevron subtrochanteric osteotomy allowed for restoration of anatomic hip center with safely functional limb lengthening, achieved correction of preoperative limp, and good functional and radiographic outcomes for 22 Crowe type-IV dislocation hips at the time of the 5- to 10-year follow-up.

Fungal spondylodiscitis in a patient recovered from H7N9 virus infection: a case study and a literature review of the differences between Candida and Aspergillus spondylodiscitis.

To report a rare case of fungal spondylodiscitis in a patient recovered from H7N9 virus infection and perform a literature review of the different characteristics of Candida and Aspergillus spondylodiscitis, we reviewed cases of spondylodiscitis caused by Candida and Aspergillus species. Data, including patients' information, pathogenic species, treatment strategy, outcomes, and relapses, were collected and summarized. The characteristics of Candida and Aspergillus spondylodiscitis were compared to see if any differences in clinical features, management, or consequences could be detected. The subject of the case study was first misdiagnosed as having a vertebral tumor, and then, following open biopsy, was diagnosed as having fungal spondylodiscitis. The patient made a good recovery following radical debridement. Seventy-seven additional cases of Candida spondylodiscitis and 94 cases of Aspergillus spondylodiscitis were identified in the literature. Patients with Candida spondylodiscitis tended to have a better outcome than patients with Aspergillus spondylodiscitis (cure rate 92.3% vs. 70.2%). Candida was found more frequently (47.8%) than Aspergillus (26.7%) in blood cultures, while neurological deficits were observed more often in patients with Aspergillus spondylodiscitis (43.6% vs. 25.6%). Candida spinal infections were more often treated by radical debridement (60.5% vs. 39.6%). Patients with Candida spondylodiscitis have better outcomes, which may be associated with prompt recognition, radical surgical debridement, and azoles therapy. A good outcome can be expected in fungal spondylodiscitis with appropriate operations and anti-fungal drugs.