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.

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.

Is Platelet-rich Plasma Injection Effective for Chronic Achilles Tendinopathy? A Meta-analysis.

BACKGROUND: Chronic Achilles tendinopathy is common in the general population, and platelet-rich plasma (PRP) is seeing increased use to treat this problem. However, studies disagree as to whether PRP confers a beneficial effect for chronic Achilles tendinopathy, and no one to our knowledge has pooled the available randomized trials in a formal meta-analysis to try to reconcile those differences. QUESTIONS/PURPOSES: In the setting of a systematic review and meta-analysis of randomized controlled trials (RCTs), we asked: Does PRP plus eccentric strength training result in (1) greater improvements in Victorian Institute of Sports Assessment-Achilles (VISA-A) scores; (2) differences in tendon thickness; or (3) differences in color Doppler activity compared with placebo (saline) injections plus eccentric strength training in patients with chronic Achilles tendinopathy? METHODS: A search of peer-reviewed articles was conducted to identify all RCTs using PRP injection with eccentric training for chronic Achilles tendinopathy in the electronic databases of PubMed, Web of Science (SCI-E/SSCI/A&HCI), and EMBASE from January 1981 to August 2017. Results were limited to human RCTs and published in all languages. Two reviewers assessed study quality using the Cochrane Collaboration risk-of-bias tool. All the included studies had low risk of bias. The primary endpoint was improvement in the VISA-A score, which ranges from 0 to 100 points, with higher scores representing increased activity and less pain; we considered the minimum clinically important difference on the VISA-A to be 12 points. Secondary outcomes were tendon thickness change (with a thicker tendon representing more severe disease), color Doppler activity (with more activity representing a poorer result), and other functional measures (such as pain and return to sports activity). Four RCTs involving 170 participants were eligible and included 85 participants treated with PRP injection and eccentric training and 85 treated with saline injection and eccentric training. The patients in both PRP and placebo (saline) groups seemed comparable at baseline. We assessed for publication bias using a funnel plot and saw no evidence of publication bias. Based on previous studies, we had 80% power to detect a 12-point difference on the VISA-A score with the available sample size in each group. RESULTS: With the numbers available, there was no difference between the PRP and saline groups regarding the primary outcome (VISA-A score: mean difference [MD], 5.3; 95% confidence interval [CI], -0.7 to 11.3; p = 0.085). Likewise, we found no difference between the PRP and saline groups in terms of our secondary outcomes of tendon thickness change (MD, 0.2 mm; 95% CI, 0.6-1.0 mm; p = 0.663) and color Doppler activity (MD, 0.1; 95% CI, -0.7 to 0.4; p = 0.695). CONCLUSIONS: PRP injection with eccentric training did not improve VISA-A scores, reduce tendon thickness, or reduce color Doppler activity in patients with chronic Achilles tendinopathy compared with saline injection. Larger randomized trials are needed to confirm these results, but until or unless a clear benefit has been demonstrated in favor of the new treatment, we cannot recommend it for general use. LEVEL OF EVIDENCE: Level I, therapeutic study.

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.

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.

Surgically treated solitary giant gluteal and retroperitoneal neurofibroma: a case report.

BACKGROUND: Giant neurofibromas in patients with neurofibromatosis type 1 involve multiple regions and are often difficult to surgically extirpate. However, surgical intervention is the most effective means for improving quality of life. The case reported herein is unique in that it involves a giant neurofibroma, involving the patient's peritoneal and pelvic cavities, retroperitoneal space, and buttock, which was causing compressive displacement of abdominal and pelvic organs. A challenging surgical intervention was required to accomplish near-total resection to relieve organ compression while preserving visceral and genitoanal function. CASE PRESENTATION: The case reported is of a patient presenting with a solitary giant retroperitoneal neurofibroma that threatened to obliterate both peritoneal and pelvic cavities and protruded conspicuously into the right gluteal region. The enormous dumbbell-shaped mass was surgically removed in three parts. Postoperative pathology studies confirmed a diagnosis of neurofibroma. Follow-up computed tomography images taken three months postoperatively revealed residual tumor in the perianal region. The patient's quality of life had measurably improved on follow-up at eight months. CONCLUSIONS: Surgical intervention in such extraordinary circumstances of a giant neurofibroma causing compressive displacement of critical organs reduces tumor burden, restores appearance and function of patient's body and internal organs, and improves the patient's quality of life.

One-Step Cartilage Repair Technique as a Next Generation of Cell Therapy for Cartilage Defects: Biological Characteristics, Preclinical Application, Surgical Techniques, and Clinical Developments.

PURPOSE: To provide a comprehensive overview of the basic science rationale, surgical technique, and clinical outcomes of 1-step cartilage repair technique used as a treatment strategy for cartilage defects. METHODS: A systematic review was performed in the main medical databases to evaluate the several studies concerning 1-step procedures for cartilage repair. The characteristics of cell-seed scaffolds, behavior of cells seeded into scaffolds, and surgical techniques were also discussed. Clinical outcomes and quality of repaired tissue were assessed using several standardized outcome assessment tools, magnetic resonance imaging scans, and biopsy histology. RESULTS: One-step cartilage repair could be divided into 2 types: chondrocyte-matrix complex (CMC) and autologous matrix-induced chondrogenesis (AMIC), both of which allow a simplified surgical approach. Studies with Level IV evidence have shown that 1-step cartilage repair techniques could significantly relieve symptoms and improve functional assessment (P < .05, compared with preoperative evaluation) at short-term follow-up. Furthermore, magnetic resonance imaging showed that 76% cases in all included case series showed at least 75% defect coverage in each lesion, and 3 studies clearly showed hyaline-like cartilage tissue in biopsy tissues by second-look arthroscopy. CONCLUSIONS: The 1-step cartilage repair technique, with its potential for effective, homogeneous distribution of chondrocytes and multipotent stem cells on the surface of the cartilage defect, is able to regenerate hyaline-like cartilage tissue, and it could be applied to cartilage repair by arthroscopy. LEVEL OF EVIDENCE: Level IV, systematic review of Level II and IV studies.

Autologous chondrocyte implantation: Is it likely to become a saviour of large-sized and full-thickness cartilage defect in young adult knee?

PURPOSE: A literature review of the first-, second- and third-generation autologous chondrocyte implantation (ACI) technique for the treatment of large-sized (>4 cm(2)) and full-thickness knee cartilage defects in young adults was conducted, examining the current literature on features, clinical scores, complications, magnetic resonance image (MRI) and histological outcomes, rehabilitation and cost-effectiveness. METHODS: A literature review was carried out in the main medical databases to evaluate the several studies concerning ACI treatment of large-sized and full-thickness knee cartilage defects in young adults. RESULTS: ACI technique has been shown to relieve symptoms and improve functional assessment in large-sized (>4 cm(2)) and full-thickness knee articular cartilage defect of young adults in short- and medium-term follow-up. Besides, low level of evidence demonstrated its efficiency and durability at long-term follow-up after implantation. Furthermore, MRI and histological evaluations provided the evidence that graft can return back to the previous nearly normal cartilage via ACI techniques. Clinical outcomes tend to be similar in different ACI techniques, but with simplified procedure, low complication rate and better graft quality in the third-generation ACI technique. CONCLUSION: ACI based on the experience of cell-based therapy, with the high potential to regenerate hyaline-like tissue, represents clinical development in treatment of large-sized and full-thickness knee cartilage defects. LEVEL OF EVIDENCE: IV.

Ifosfamide-loaded poly (lactic-co-glycolic acid) PLGA-dextran polymeric nanoparticles to improve the antitumor efficacy in Osteosarcoma.

BACKGROUND: Osteosarcoma is a typical bone cancer that primarily affects adolescents. The therapeutic activity of drugs is limited by their severe drug-related toxicities, therefore, a therapeutic approach which is less toxic and highly effective in tumor is of utmost importance. METHOD: In this study, ifosfamide-loaded poly (lactic-co-glycolic acid) (PLGA)-dextran polymeric nanoparticles (PD/IFS) was developed and studied its anticancer efficacy against multiple osteosarcoma cancer cells. The drug-loaded nanoparticle was characterized for physical and biological characterizations. RESULTS: The formulated PD/IFS showed a high drug loading capacity and displayed a pH-sensitive release pattern, with a sustained release profile of the IFS. PD/IFS nanoparticles exhibited remarkable in vitro anticancer activity comparable to that of free IFS solution in a concentration dependent manner in MG63 and Saos-2 cancer cells. PLGA-dextran by itself did not affect cell viability of cancer cells indicating its excellent biocompatibility. The formulation exhibited significantly higher PARP and caspase-3/7 expression in both the cancer cells. CONCLUSION: Our study successfully demonstrated that nanoparticulate encapsulation of antitumor agent will increase the therapeutic efficacy and exhibit a greater induction of apoptosis and cell death.

Long non-coding RNA-DANCR in human circulating monocytes: a potential biomarker associated with postmenopausal osteoporosis.

Osteoporosis is a common disease characterized by low bone mineral density (BMD) and low trauma fractures, mainly resulting from exceeding bone resorption by osteoclasts over bone formation by osteoblasts. Circulating monocytes are directly involved in osteoclastogenesis, and lncRNAs are believed to be involved in the osteoblast differentiation. However, no study has been conducted to identify the roles of lncRNA in circulating monocytes associated with human osteoporosis. In this study, we found significant upregulation of DANCR in the blood mononuclear cells (MNCs) from low-BMD patients with the qRT-PCR analyses. We further found that DANCR promoted the expression of IL6 and TNF-α at both mRNA level and protein level in MNCs. After deletion of DANCR with siRNAs, the levels of IL6 and TNF-α are decreased in the MNCs from low-BMD postmenopausal women. Moreover, DANCR level was correlated with IL6 and TNF-α in postmenopausal women with low BMD. Furthermore, we found that DANCR-induced IL6 and TNF-α in MNCs had bone-resorbing activity. These results indicate that DANCR is involved in the pathology of osteoporosis and may be as a biomarker for postmenopausal osteoporosis.

Efficacy of platelet-rich plasma in arthroscopic repair of full-thickness rotator cuff tears: a meta-analysis.

BACKGROUND: The use of platelet-rich plasma (PRP) is an innovative clinical therapy, especially in arthroscopic rotator cuff repair. The purpose of this study was to compare the clinical improvement and tendon-to-bone healing with and without PRP therapy in arthroscopic rotator cuff repair. METHODS: A systematic search was done in the major medical databases to evaluate the studies using PRP therapy (PRP+) or with no PRP (PRP-) for the treatment of patients with rotator cuff tears. We reviewed clinical scores such as the Constant score, the American Shoulder and Elbow Surgeons score, the University of California at Los Angeles (UCLA) Shoulder Rating Scale, the Simple Shoulder Test, and the failure-to-heal rate by magnetic resonance imaging between PRP+ and PRP- groups. RESULTS: Five studies included in this review were used for a meta-analysis based on data availability. There were no statistically significant differences between PRP+ and PRP- groups for overall outcome scores (P > .05). However, the PRP+ group exhibited better healing rates postoperatively than the PRP- group (P = .03) in small/moderate full-thickness tears. CONCLUSION: The use of PRP therapy in full-thickness rotator cuff repairs showed no statistically significant difference compared with no PRP therapy in clinical outcome scores, but the failure-to-heal rate was significantly decreased when PRP was used for treatment of small-to-moderately sized tears. PRP therapy may improve tendon-to-bone healing in patients with small or moderate rotator cuff tears.

Is Early Controlled Motion and Weightbearing Recommended for Nonoperatively Treated Acute Achilles Tendon Rupture? A Systematic Review and Meta-analysis.

BACKGROUND: There is disagreement as to whether early controlled motion and weightbearing confer a beneficial effect for nonoperatively treated acute Achilles tendon rupture (ATR) compared with immobilization and late weightbearing. PURPOSE: To conduct a meta-analysis of randomized controlled trials (RCTs) to determine whether early controlled motion and weightbearing results in different outcomes compared with immobilization and late weightbearing for nonoperatively treated patients with acute ATR. STUDY DESIGN: Systematic review; Level of evidence, 1. METHODS: We conducted a search in the PubMed, Web of Science, and EMBASE databases for relevant RCTs in humans from January 1981 to August 2020. The primary outcome was the Achilles Tendon Total Rupture Score (ATRS) at 1-year follow-up. The secondary outcomes were the rerupture rate, return to sports activity and work, and the heel-rise work (limb symmetry index [LSI]). Study quality was assessed using the Cochrane Collaboration risk of bias tool. RESULTS: Included were 7 RCTs involving 424 participants (n = 215 treated with early controlled motion and weightbearing [early group], n = 209 treated with immobilization and late weightbearing [late group]). The quality assessment indicated a low risk of bias in all included RCTs. There was no difference between the early and late groups regarding the ATRS (mean difference [MD], -0.220; 95% CI, -4.489 to 4.049; P = .920). Likewise, we found no difference between the 2 groups in terms of the rerupture rate (odds ratio [OR], 1.107; 95% CI, 0.552 to 2.219; P = .775), the number of patients who returned to sports (OR, 0.766; 95% CI, 0.438 to 1.341; P = .351) and returned to work (OR, 0.706; 95% CI, 0.397 to 1.253; P = .234), the time to return to work (MD, -2.802 days; 95% CI, -6.525 to 0.921 days; P = .140), or the heel-rise work LSI (MD, -0.135; 95% CI, -6.243 to 5.973; P = .965). CONCLUSION: No significant differences were found between early controlled motion and weightbearing compared with immobilization and late weightbearing regarding the ATRS, the rerupture rate, return to sports activity and work, and the heel-rise work in nonoperatively treated patients with acute ATR.

Analysis of the main soft tissue stress associated with flexible flatfoot deformity: a finite element study.

A better understanding of soft tissue stress and its role in supporting the medial longitudinal arch in flexible flatfoot could help to guide the clinical treatment. In this study, a 3-Dimensional finite element (FE) foot model was reconstructed to measure the stress of the soft tissue, and its variation in different scenarios related to flexible flatfoot. All bones, cartilages, ligaments and related tendons around the ankle, and fat pad were included in the finite element model. The equivalent stress on the articular surface of the joints in the medial longitudinal arch and the maximum principal stress of the ligaments around the ankle were obtained. The results show that the plantar fascia (PF) is the main tissue in maintaining the medial longitudinal arch. The equivalent stress of all the joints in the medial longitudinal arch increases when the PF attenuation and the talonavicular joint increases, while other joints decreases when all the three tissue attenuation. Moreover, the maximum principal stress variation of calcaneofibular ligament is largest when the PF attenuation and the tibionavicular ligament and posterior tibiotalar ligament are largest when the posterior tibial tendon (PTT) attenuation. The maximum principal stress variation of tibionavicular ligament and posterior tibiotalar ligament are even larger when all the three tissue attenuation. These findings support that the PF is the main factor in maintaining the medial longitudinal arch. The medial longitudinal arch collapse mainly affects the talonavicular joint and the calcaneofibular ligament, the tibionavicular ligament and the posterior tibiotalar ligament. This approach could help to improve the understanding of adult-acquired flatfoot deformity (AAFD).

Effect of soft inflatable orthosis on the medial longitudinal arch in patients with flexible flatfoot deformity.

BACKGROUND: Orthoses can stabilize the foot and restore the medial longitudinal arch for symptomatic flexible flatfoot. However, the effectiveness of orthoses remains controversial. The purpose of this study was to evaluate effectiveness of a customized soft inflatable orthosis on the medial longitudinal arch of flexible flatfoot patients under load. METHODS: We obtained CT scans of the feet of 14 healthy volunteers and 14 patients with flexible flatfoot under non- and simulated weight-bearing conditions. Then CT scans under the same conditions were taken for patients with flexible flatfoot equipped with soft inflatable orthosis. Three-dimensional models of the medial longitudinal arch and hindfoot were constructed from CT images. The three-dimensional mobility of the medial longitudinal arch joints under load was compared between patients with flexible flatfoot equipped with soft inflatable orthosis or not. FINDINGS: From non- to simulated weight-bearing condition, the eversion and dorsiflexion of the talocalcaneal joint, the eversion of the talonavicular joint, the abduction and dorsiflexion of the cuneonavicular joint, and the dorsiflexion of the first tarsometatarsal joint were significantly larger in patients with flexible flatfoot than healthy volunteers. The customized soft inflatable orthosis could reduce the eversion of the talonavicular joint and the eversion and dorsiflexion of the talocalcaneal joint. INTERPRETATION: The soft inflatable orthosis is effective to improve medial longitudinal arch height and reduce excessive mobility of joints for flexible flatfoot deformity. The results of this study could provide evidence for the optimal orthosis design to treat flexible flatfoot in the future.

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.

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.

Magnetically Actuated Manipulation and Its Applications for Cartilage Defects: Characteristics and Advanced Therapeutic Strategies.

For the fact that articular cartilage is a highly organized and avascular tissue, cartilage defects are limited to spontaneously heal, which would subsequently progress to osteoarthritis. Many methods have been developed to enhance the ability for cartilage regeneration, among which magnetically actuated manipulation has attracted interests due to its biocompatibility and non-invasive manipulation. Magnetically actuated manipulation that can be achieved by introducing magnetic nanoparticles and magnetic field. This review summarizes the cutting-edge research on the chondrogenic enhancements via magnetically actuated manipulation, including cell labeling, cell targeting, cell assembly, magnetic seeding and tissue engineering strategies.

Diagnosis and treatment of spinal tuberculosis after liver transplantation.

BACKGROUND: Spinal tuberculosis is a common disease in orthopedic clinical practice; however, it is seldom reported after organ transplantation. The aim of this study was to investigate the diagnosis and treatment of spinal tuberculosis after organ transplantation. METHOD: Two cases were diagnosed as spinal tuberculosis after liver transplantation and were treated with socarboxazide, rifampicin, streptomycin and ethambutol for more than one year. RESULTS: After treatment with anti-tuberculosis drugs for several months, the symptoms of both patients clearly improved. Back pain disappeared, and erythrocyte sedimentation and body temperature returned to normal. CONCLUSIONS: We should highly suspect spinal tuberculosis if notalgia and night sweats are present after organ transplantation. Anti-tuberculosis therapy is an effective treatment for spinal tuberculosis after organ transplantation.

Neuroprotective effects of rapamycin on spinal cord injury in rats by increasing autophagy and Akt signaling.

Rapamycin treatment has been shown to increase autophagy activity and activate Akt phosphorylation, suppressing apoptosis in several models of ischemia reperfusion injury. However, little has been studied on the neuroprotective effects on spinal cord injury by activating Akt phosphorylation. We hypothesized that both effects of rapamycin, the increased autophagy activity and Akt signaling, would contribute to its neuroprotective properties. In this study, a compressive spinal cord injury model of rat was created by an aneurysm clip with a 30 g closing force. Rat models were intraperitoneally injected with rapamycin 1 mg/kg, followed by autophagy inhibitor 3-methyladenine 2.5 mg/kg and Akt inhibitor IV 1 µg/kg. Western blot assay, immunofluorescence staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay were used to observe the expression of neuronal autophagy molecule Beclin 1, apoptosis-related molecules Bcl-2, Bax, cytochrome c, caspase-3 and Akt signaling. Our results demonstrated that rapamycin inhibited the expression of mTOR in injured spinal cord tissue and up-regulated the expression of Beclin 1 and phosphorylated-Akt. Rapamycin prevented the decrease of bcl-2 expression in injured spinal cord tissue, reduced Bax, cytochrome c and caspase-3 expression levels and reduced the number of apoptotic neurons in injured spinal cord tissue 24 hours after spinal cord injury. 3-Methyladenine and Akt inhibitor IV intervention suppressed the expression of Beclin-1 and phosphorylated-Akt in injured spinal cord tissue and reduced the protective effect of rapamycin on apoptotic neurons. The above results indicate that the neuroprotective effect of rapamycin on spinal cord injury rats can be achieved by activating autophagy and the Akt signaling pathway.