The potential therapeutic roles of dental pulp stem cells in spinal cord injury.

Spinal cord injury (SCI) can lead to serious functional disorders, which have serious impacts on patients and society. The current traditional treatments of SCI are not effective the injured spinal cord is difficult to repair and regenerate. In recent years, stem cell transplantation for the treatment of SCI has been a hot research topic. Dental pulp stem cells have strong abilities of self-renewal and multi-directional differentiation, and have been applied for tissue engineering and regenerative medicine. And dental pulp stem cells have certain advantages in neuro-regenetation, bringing new hope to biotherapy for SCI. This article reviews the characteristics of dental pulp stem cells and their research progress in the treatment of SCI.

Oblique Lumbar Interbody Fusion at L5-S1 Segment Through an Approach Between the Psoas Muscle and the Great Vessels.

Over the years, the oblique lateral interbody fusion (OLIF) technique has gained significant recognition for treating various spinal conditions in lumbar segments L2-L5. However, the adoption of OLIF for the L5-S1 segment has not been widely embraced by the spinal surgery community, given that significant concerns remain regarding the applicability of OLIF for lumbosacral fusion. In this study, a cohort of 20 patients underwent interbody fusion at the L5-S1 level using the OLIF technique through a single retroperitoneal oblique approach positioned between the Psoas muscle and the great vessels. The procedure involved discectomy and endplate preparation accomplished through a surgical window created on the anterolateral side of the L5-S1 disc. For secure interbody fusion cage placement, a supplementary cage insertion approach was employed. All patients were followed up for a minimum of 12 months. The mean preoperative visual analog scale (VAS) score for lower back pain was 6.3 ± 1.5 and experienced a significant reduction to 1.2 ± 0.8 at 12 months. The VAS score for lower limb pain significantly decreased from 5.6 ± 1.4 preoperatively to 0.8 ± 0.3 at 12 months after the surgery. Furthermore, the preoperative Oswestry disability index (ODI) improved from 82.4% ± 16.2% to 8.1% ± 2.0% at 12 months. Radiographic evaluations after surgery confirmed improved lumbosacral junction reconstruction for all patients. At the final follow-up, successful bony fusion was observed in all cases. Based on these findings, the OLIF technique for L5-S1 fusion represents an attainable approach for lumbosacral reconstruction. The procedure's success hinges on a comprehensive preoperative plan and precise intraoperative techniques.

Biochanin A attenuates spinal cord injury in rats during early stages by inhibiting oxidative stress and inflammasome activation.

JOURNAL/nrgr/04.03/01300535-202409000-00038/figure1/v/2024-01-16T170235Z/r/image-tiff Previous studies have shown that Biochanin A, a flavonoid compound with estrogenic effects, can serve as a neuroprotective agent in the context of cerebral ischemia/reperfusion injury; however, its effect on spinal cord injury is still unclear. In this study, a rat model of spinal cord injury was established using the heavy object impact method, and the rats were then treated with Biochanin A (40 mg/kg) via intraperitoneal injection for 14 consecutive days. The results showed that Biochanin A effectively alleviated spinal cord neuronal injury and spinal cord tissue injury, reduced inflammation and oxidative stress in spinal cord neurons, and reduced apoptosis and pyroptosis. In addition, Biochanin A inhibited the expression of inflammasome-related proteins (ASC, NLRP3, and GSDMD) and the Toll-like receptor 4/nuclear factor-κB pathway, activated the Nrf2/heme oxygenase 1 signaling pathway, and increased the expression of the autophagy markers LC3 II, Beclin-1, and P62. Moreover, the therapeutic effects of Biochanin A on early post-spinal cord injury were similar to those of methylprednisolone. These findings suggest that Biochanin A protected neurons in the injured spinal cord through the Toll-like receptor 4/nuclear factor κB and Nrf2/heme oxygenase 1 signaling pathways. These findings suggest that Biochanin A can alleviate post-spinal cord injury at an early stage.

The effects of melatonin in the treatment of acute brachial plexus compression injury in rats.

Introduction: Brachial plexus injury (BPI) is one of the most destructive peripheral nerve injuries and there is still a lack of effective treatment. Methods: This study was conducted to evaluate the effects of melatonin in the treatment of acute brachial plexus compression injury in rats using histopathological, histomorphometric, immunohistochemical and electrophysiological methods. Forty-eight adult male Sprague Dawley rats were randomly allocated into three groups: sham, melatonin and vehicle groups. The brachial plexus compression injury model was performed by a vascular clamp. Melatonin group received intraperitoneal injection of melatonin at doses of 10 mg/kg for 21 days after crush injury. The conduction velocity and amplitude of compound muscle action potential (CAMP) in the regenerated nerve, and nerve histomorphometry, as well as levels of myelin protein zero (P0) protein of the crush region were assessed. Results: Compared with the vehicle group, the melatonin group which reported significant increased CMAP conduction velocity and amplitude also showed thicker myelin sheath and lower levels of P0 protein. Discussion: Our results suggest that melatonin effectively promotes nerve regeneration and improves the function of damaged nerves. Melatonin treatment is a promising strategy for the treatment of acute brachial plexus compression injury.

A new injectable quick hardening anti-collapse bone cement allows for improving biodegradation and bone repair.

The development of injectable cement-like biomaterials via a minimally invasive approach has always attracted considerable clinical interest for modern bone regeneration and repair. Although α-tricalcium phosphate (α-TCP) powders may readily react with water to form hydraulic calcium-deficient hydroxyapatite (CDHA) cement, its long setting time, poor anti-collapse properties, and low biodegradability are suboptimal for a variety of clinical applications. This study aimed to develop new injectable α-TCP-based bone cements via strontium doping, α-calcium sulfate hemihydrate (CSH) addition and liquid phase optimization. A combination of citric acid and chitosan was identified to facilitate the injectable and anti-washout properties, enabling higher resistance to structure collapse. Furthermore, CSH addition (5 %-15 %) was favorable for shortening the setting time (5-20 min) and maintaining the compressive strength (10-14 MPa) during incubation in an aqueous buffer medium. These α-TCP-based composites could also accelerate the biodegradation rate and new bone regeneration in rabbit lateral femoral bone defect models in vivo. Our studies demonstrate that foreign ion doping, secondary phase addition and liquid medium optimization could synergistically improve the physicochemical properties and biological performance of α-TCP-based bone cements, which will be promising biomaterials for repairing bone defects in situations of trauma and diseased bone.

Mesoporous polydopamine nanoparticles for sustained release of rapamycin and reactive oxygen species scavenging to synergistically accelerate neurogenesis after spinal cord injury.

Spinal cord injury (SCI) is an intractable condition with complex pathological processes and poor prognosis. Reactive oxygen species (ROS) generation induced by the mammalian target of the rapamycin (mTOR) protein is one of the causes of secondary inflammation of SCI. Rapamycin (Rapa) is a pharmacological inhibitor of mTOR, which can inhibit ROS overproduction mediated by abnormal activation of the mTOR protein. Polydopamine, as a nanocarrier with excellent biological safety, has been reported to possess satisfactory ROS scavenging ability. Therefore, we designed a mesoporous polydopamine nanoparticle loaded with Rapa (mPDA@Rapa) for combination therapy, which simultaneously inhibited abnormally activated mTOR-mediated ROS production and eliminated already generated ROS. The synthesized mPDA nanoparticles could realize the effective encapsulation and sustained release of Rapa due to their mesoporous cavities and a hydrophobic benzene ring structure. In vitro experiments proved that mPDA@Rapa nanoparticles had a good ROS scavenging ability towards hydrogen peroxide and hydroxyl radicals. Furthermore, mPDA@Rapa also showed a good therapeutic effect in SCI model rats, which was evidenced by a smaller injury cavity, more coordinated hind limb movements, and a higher degree of neurogenesis and tissue regeneration. Our work provides a combined strategy to inhibit ROS overproduction and eliminate excess ROS, with potential applications not only in SCI, but also in other ROS-induced inflammations.

A multi-center retrospective comparative study of third generation Ceramic-on- Ceramic total hip arthroplasty in patients younger than 45 years with or without the sandwich liner: A ten-year minimum.

BACKGROUND: Ceramic-on-ceramic couplings are attractive alternative bearing surfaces that have been reported to eliminate or reduce problems related to polyethylene wear debris. However, the material in THA still remains one of the major concerns about the risk of fracture, due to its brittleness. OBJECTIVE: The present study aims at reporting the fracture rate of a series of ceramic-on-ceramic THAs with use of the sandwich liner combined with a ceramic femoral head, and attempt to detect the relative risk factors, possible cause and assesse the medium-term clinical results. METHODS: We retrospectively evaluated 282 patients (300 hips) with use of the sandwich liner ceramic-on-ceramic THA between 2001 and 2009 at three-centers. Patient assessment was based on demographic factors, including age, weight, gender and body-mass index. All patients were evaluated clinically and radio-graphically or computed tomography in consideration of dislocation, osteolysis, periprosthetic fracture, infection, loosening and implant fracture. RESULTS: five ceramic sandwich liners fracture (1.7%) were observed at an average of 7.3 years follow-up. These factors were irrelevant to the ceramic liner fracture, including age (p = 0.205), weight (p = 0.241), gender (p = 0.553), body-mass index (p = 0.736), inclination (p = 0.727), and anteversion (p = 0.606). The overall survival was 91.4% at 12 years with revision as the endpoint. Other complications included dislocation in two, perprosthetic fracture in two and osteolysis in eight hips. No hip had aseptic loosening of the implants was seen. CONCLUSIONS: We found that the sandwich liner may be lead to a high rate of alumina fracture and osteolysis. We have discontinued the use of sandwich liner with THA since 2009.

The potential roles of dental pulp stem cells in peripheral nerve regeneration.

Peripheral nerve diseases are significantly correlated with severe fractures or trauma and surgeries, leading to poor life quality and impairment of physical and mental health. Human dental pulp stem cells (DPSCs) are neural crest stem cells with a strong multi-directional differentiation potential and proliferation capacity that provide a novel cell source for nerve regeneration. DPSCs are easily extracted from dental pulp tissue of human permanent or deciduous teeth. DPSCs can express neurotrophic and immunomodulatory factors and, subsequently, induce blood vessel formation and nerve regeneration. Therefore, DPSCs yield valuable therapeutic potential in the management of peripheral neuropathies. With the purpose of summarizing the advances in DPSCs and their potential applications in peripheral neuropathies, this article reviews the biological characteristics of DPSCs in association with the mechanisms of peripheral nerve regeneration.

Chemogenetic stimulation of proprioceptors remodels lumbar interneuron excitability and promotes motor recovery after SCI.

Motor recovery after severe spinal cord injury (SCI) is limited due to the disruption of direct descending commands. Despite the absence of brain-derived descending inputs, sensory afferents below injury sites remain intact. Among them, proprioception acts as an important sensory source to modulate local spinal circuits and determine motor outputs. Yet, it remains unclear whether enhancing proprioceptive inputs promotes motor recovery after severe SCI. Here, we first established a viral system to selectively target lumbar proprioceptive neurons and then introduced the excitatory Gq-coupled Designer Receptors Exclusively Activated by Designer Drugs (DREADD) virus into proprioceptors to achieve specific activation of lumbar proprioceptive neurons upon CNO administration. We demonstrated that chronic activation of lumbar proprioceptive neurons promoted the recovery of hindlimb stepping ability in a bilateral hemisection SCI mouse model. We further revealed that chemogenetic proprioceptive stimulation led to coordinated activation of proprioception-receptive spinal interneurons and facilitated transmission of supraspinal commands to lumbar motor neurons, without affecting the regrowth of proprioceptive afferents or brain-derived descending axons. Moreover, application of 4-aminopyridine-3-methanol (4-AP-MeOH) that enhances nerve conductance further improved the transmission of supraspinal inputs and motor recovery in proprioception-stimulated mice. Our study demonstrates that proprioception-based combinatorial modality may be a promising strategy to restore the motor function after severe SCI.

Hypoxia inducible factor-1 (HIF-1α) reduced inflammation in spinal cord injury via miR-380-3p/ NLRP3 by Circ 0001723.

BACKGROUND: Spinal cord injury (SCI) is a severe central nervous system trauma. The present study aimed to evaluate the effect of HIF-1α on inflammation in spinal cord injury (SCI) to uncover the molecular mechanisms of anti-inflammation. RESULTS: HIF-1α was reduced in SCI model rats and HIF-1α activation reduced TNF-α, IL-1ß, IL-6 and IL-18 levels in SCI model rats. Meanwhile, Circ 0001723 expression was down-regulated and miR-380-3p expression was up-regulated in SCI model rats. In vitro model, down-regulation of Circ 0001723 promoted TNF-α, IL-1ß, IL-6 and IL-18 levels, compared with control negative group. However, over-expression of Circ 0001723 reduced TNF-α, IL-1ß, IL-6 and IL-18 levels in vitro model. Down-regulation of Circ 0001723 suppressed HIF-1α protein expressions and induced NLRP3 and Caspase-1 protein expressions in vitro model by up-regulation of miR-380-3p. Next, inactivation of HIF-1α reduced the pro-inflammation effects of Circ 0001723 in vitro model. Then, si-NLRP3 also inhibited the pro-inflammation effects of Circ 0001723 in vitro model via promotion of autophagy. CONCLUSIONS: We concluded that HIF-1α reduced inflammation in spinal cord injury via miR-380-3p/ NLRP3 by Circ 0001723.

Hypoxia inducible factor-1 (HIF-1α) reduced inflammation in spinal cord injury via miR-380-3p/ NLRP3 by Circ 0001723

BACKGROUND: Spinal cord injury (SCI) is a severe central nervous system trauma. The present study aimed to evaluate the effect of HIF-1α on inflammation in spinal cord injury (SCI) to uncover the molecular mechanisms of anti-inflammation. RESULTS: HIF-1α was reduced in SCI model rats and HIF-1α activation reduced TNF-α, IL-1ß, IL-6 and IL-18 levels in SCI model rats. Meanwhile, Circ 0001723 expression was down-regulated and miR-380-3p expression was up-regulated in SCI model rats. In vitro model, down-regulation of Circ 0001723 promoted TNF-α, IL-1ß, IL-6 and IL-18 levels, compared with control negative group. However, over-expression of Circ 0001723 reduced TNF-α, IL-1ß, IL-6 and IL-18 levels in vitro model. Down-regulation of Circ 0001723 suppressed HIF-1α protein expressions and induced NLRP3 and Caspase-1 protein expressions in vitro model by up-regulation of miR-380-3p. Next, inactivation of HIF-1α reduced the pro-inflammation effects of Circ 0001723 in vitro model. Then, si-NLRP3 also inhibited the pro-inflammation effects of Circ 0001723 in vitro model via promotion of autophagy. CONCLUSIONS: We concluded that HIF-1α reduced inflammation in spinal cord injury via miR-380-3p/ NLRP3 by Circ 0001723.

Acute and chronic traumatic diaphragmatic hernia: 10 years' experience.

Controversy persists regarding many aspects of traumatic diaphragmatic hernia (TDH). We aimed to understand why some traumatic diaphragmatic injuries present with chronic hernia and to evaluate diagnosis and treatment options. Fifty acute and 19 chronic TDH patients were diagnosed and treated at our institution over a 10-year period. Clinical data from these two groups were analyzed statistically and compared. Chronic TDH patients had a significantly lower Injury Severity Score than acute TDH patients (10.26 ± 2.68 vs. 26.92 ± 4.79, P < 0.001). The most common surgical approach for acute and chronic TDH was thoracotomy and laparotomy, respectively. The length of the diaphragmatic rupture was significantly shorter in chronic TDH patients than acute TDH patients (6.00 ± 1.94 cm vs. 10.71 ± 3.30 cm, P < 0.001). The mean length of hospital stay was significantly longer for acute TDH patients than chronic TDH patients (41.18 ± 31.02 days vs. 16.65 ± 9.61 days, P = 0.002). In conclusion, milder trauma and a smaller diaphragmatic rupture were associated with delayed diagnosis. A thoraco-abdominal computed tomography scan is needed for patients with periphrenic injuries to avoid delayed diagnosis of TDH. Improved awareness and understanding of diaphragmatic injuries will increase the rate of early diagnosis and improve prognosis.

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.

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.

Knockdown of miR-372 Inhibits Nerve Cell Apoptosis Induced by Spinal Cord Ischemia/Reperfusion Injury via Enhancing Autophagy by Up-regulating Beclin-1.

To investigate the role of miR-372/Beclin-1 on nerve cell apoptosis induced by spinal cord ischemia/reperfusion injury (SCII). We established in vivo and in vitro SCII model. MiR-372 and Beclin-1 expressions in spinal cord tissues of SCII rats and SCII nerve cells were measured. The cell apoptosis was detected by flow cytometry. MiR-372 inhibitor was used to reduce miR-372 expression. Dual luciferase reporter assay was used to confirm the interaction between miR-372 and Beclin-1. MiR-372 expression in spinal cord tissues of SCII rats and SCII nerve cells was increased, while Beclin-1 expression was decreased. Knockdown of miR-372 could inhibit SCII nerve cell apoptosis. In addition, MiR-372 could negatively regulate Beclin-1 expression. Autophagy inhibitor could inhibit autophagy to promote the apoptosis of SCII nerve cells through decreasing Beclin-1, while interference of miR-372 changed the effect of autophagy inhibitor. Interference of miR-372 could reduce nerve cell apoptosis in SCII via increasing autophagy by up-regulating Beclin-1.

Neuroprotection by Paeoniflorin against Nuclear Factor Kappa B-Induced Neuroinflammation on Spinal Cord Injury.

BACKGROUND: Acute spinal cord injury (SCI) is one of the most common and devastating causes of sensory or motor dysfunction. Nuclear factor-kappa B(NF-κB)-mediated neuroinflammatory responses, in addition to nitric oxide (NO), are key regulatory pathways in SCI. Paeoniflorin (PF), a major active component extracted from Paeonia roots, has been suggested to exert neuroprotective effects in the central nervous system. However, whether PF could improve the motor function after SCI in vivo is still unclear. METHOD: Immunohistochemical analysis, western blot, real-time quantitative PCR, immunofluorescence staining, and histopathological and behavioral evaluation were used to explore the effects of paeoniflorin after SCI for 14 days. RESULTS: In this study, PF treatment significantly inhibited NF-κB activation and downregulated the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2(COX-2), and Nogo-A. Comparing behavioral and histological changes in SCI and PF treatment groups, we found that PF treatment improved motor function recovery, attenuated the histopathological damage, and increased neuronal survival in the SCI model. PF treatment also reduced expression levels of Bax and c-caspase-3 and increased the expression level of Bcl-2 and cell viabilities. Upregulation of TNF-α, IL-6, and IL-1ß after injury was also prevented by PF. CONCLUSION: These results suggest that the neuroprotective effects of PF are related to the inhibition of the NF-κB signaling pathway. And PF may be a therapeutic strategy in spinal cord injury.

Refracture of osteoporotic vertebral body after treatment by balloon kyphoplasty: Three cases report.

RATIONALE: Balloon kyphoplasty is a widely accepted treatment of osteoporotic vertebral compression fractures (OVCFs) with good results and a low risk for complications. A refracture of previously treated vertebra is a relatively rare condition. PATIENT CONCERNS: We reported our 3 cases and reviewed all relevant literatures of 11 cases with refracture of osteoporotic vertebral body after kyphoplasty. DIAGNOSES: Follow-up radiographs or magnetic resonance imaging examination confirmed refractures of previously treated vertebrae after kyphoplasty. INTERVENTIONS: One patient with 1 refracture of osteoporotic vertebral body after kyphoplasty was treated conservatively, but the other 2 patients were treated surgically because of multiple vertebral fractures or neurological deficits. OUTCOMES: The average age of the patients was 76.8 years (range, 63-86 years). All the patients had severe osteoporosis with a mean T-score of -3.46 (range -5.0 to -3.0). The sites of refractures are in the lumbar and thoracolumbar regions. Severe osteoporosis, the presence of intravertebral cleft, and a solid lump injection pattern of polymethylmethacrylate would result in insufficient strengthening effects of cement augmentation and therefore increased the likelihood of refractures of the kyphoplasty vertibrae. LESSONS: Patients with OVCFs and intravertebral cleft who did not obtain complete pain-relief at the treated vertebral level after kyphoplasty should be strictly followed up. Early finding of this condition and rapid intervention might contribute to avoiding the occurrence of the cemented vertebral refracture after kyphoplasty. Conservative treatments such as back brace and antiosteoporotic medications were strongly recommended.

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.

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.