LncRNA HCG18 promotes osteosarcoma growth by enhanced aerobic glycolysis via the miR-365a-3p/PGK1 axis.

BACKGROUND: Osteosarcoma (OS) is a common primary bone malignancy. Long noncoding RNA HCG18 is known to play an important role in a variety of cancers. However, its role in OS and relevant molecular mechanisms are unclear. METHODS: Real-time quantitative PCR was performed to determine the expression of target genes. Function experiments showed the effects of HCG18 and miR-365a-3p on OS cell growth. RESULTS: HCG18 expression was increased in OS cell lines. Moreover, in vitro and in vivo experiments demonstrated that HCG18 knockdown inhibited OS cell proliferation. Mechanistically, HCG18 was defined as a competing endogenous RNA by sponging miR-365a-3p, thus elevating phosphoglycerate kinase 1 (PGK1) expression by directly targeting its 3'UTR to increase aerobic glycolysis. CONCLUSION: HCG18 promoted OS cell proliferation via enhancing aerobic glycolysis by regulating the miR-365a-3p/PGK1 axis. Therefore, HCG18 may be a potential target for OS treatment.

Classification and morphology of hyperextension tibial plateau fracture.

PURPOSE: This study was aimed at analyzing the incidence and characteristics of hyperextension tibial plateau fractures (HTPFs) by using a computed tomography (CT)-based "four-column and nine-segment" classification. METHODS: In the coronal plane, HTPFs are divided into four types: pure hyperextension, hyperextension-varus, hyperextension-valgus, and hyperextension-bicondylar. Fractures in the sagittal plane were divided into three types: type 1, pure depression; type 2, cleavage extending to the posterior cortex with no displacement; and type 3, cleavage extending to the posterior cortex with a significant displacement. A retrospective analysis of CT images of the tibial plateau fractures from December 2007 to December 2021 was conducted. Fracture mapping was analyzed and drawn using the new classification system. RESULTS: A total of 136 (10.9%, 136/1253) fractures fulfilled the radiographic criteria for HTPF pattern in 136 knees (53.5 ± 13.3 years). There were 11 knees with pure hyperextension fracture (8.1%), 23 with hyperextension-varus fracture (16.9%), 46 with hyperextension-valgus fracture (33.8%), and 56 with hyperextension-bicondylar fracture (41.2%) in the coronal plane. Furthermore, there were 64 (47.1%), 47 (34.6%), and 25 (18.4%) cases of type 1, type 2, and type 3 fractures, respectively, in the sagittal plane. In the three-dimensional heat map, the fracture lines were mainly located at the anterior rim of the tibial plateau, while the posterior articular surface was rarely involved. CONCLUSIONS: The main manifestations of HTPF are anterior compression and posterior avulsion injury. The CT-based four-column and nine-segment classification system could be used to categorize the injury characteristics of HTPF in the coronal and sagittal planes.

Analysis of Correlation Between Age and Cervical Facet Joint Degeneration and Modic Changes in Patients with Cervical Spondylotic Myelopathy.

BACKGROUND Because facet joints move with the disc, changes in vertebral bodies occur simultaneously with progression of degeneration of cervical facet joints. This study investigated age-related differences in cervical facet joint abnormalities and multi-dimensional characteristics of MCs in patients with cervical spondylotic myelopathy. MATERIAL AND METHODS Forty-five patients underwent both magnetic resonance imaging (MRI) and computed tomography (CT) of the cervical spine. Axial and sagittal parameter changes from C3 to C7, including facet orientation (FO) and facet tropism (FT), and Modic changes (MCs), were evaluated and documented preoperatively, and we also measured the heights and diameters of MCs and performed correlation analysis and established linear regression models. RESULTS The axial facet orientation increased slightly from C3 66.5 (11.4) to C7 89.9 (19). The sagittal facet orientation and facet tropism increased between C3-C4 and C6-C7, but it decreased between C4 to C6. The MCs volume decreased from C3 to C4 and increased from C4 to C7. There was a gradual decrease of FO and FT from C3 to C5 and a gradual increase of these 2 angles from C5 to C7 in all age groups. The lowest values of FO and FT were detected at C5, while the highest values of FO and FT were detected at C7. CONCLUSIONS Age was negatively correlated with the axial, sagittal, and coronal cervical facet orientation, especially at C4/5 level. The FT with respect to the axial and sagittal plane from C5 to C6 increased with age.

Long non-protein coding RNA DANCR functions as a competing endogenous RNA to regulate osteoarthritis progression via miR-577/SphK2 axis.

Long noncoding RNAs (lncRNAs) have been known to be involved in multiple diverse diseases, including osteoarthritis (OA). This study aimed to explore the role of differentiation antagonizing non-protein coding RNA (DANCR) in OA and identify the potential molecular mechanisms. The expression of DANCR in cartilage samples from patients with OA was detected using quantitative reverse transcription-polymerase chain reaction. The effects of DANCR on the viability of OA chondrocytes and apoptosis were explored using cell counting kit 8 assay and flow cytometry assay, respectively. Additionally, the interaction among DANCR, miR-577, and SphK2 was explored using dual-luciferase reporter and RIP assays. The present study found that DANCR was significantly upregulated in patients with OA. Functional assays demonstrated that DANCR inhibition suppressed the proliferation of OA chondrocytes and induced cell apoptosis. The study also showed that DANCR acted as a competitive endogenous RNA to sponge miR-577, which targeted the mRNA of SphK2 to regulate the survival of OA chondrocytes. In conclusion, the study revealed that lncRNA DANCR might promote the proliferation of OA chondrocytes and reduce apoptosis through the miR-577/SphK2 axis. Thus, lncRNA DANCR might be considered as a potential therapeutic target for OA treatment.

The effects of spinal cord injury on bone healing in patients with femoral fractures.

BACKGROUND: Orthopedic literature states that fractures of long bones, when associated with traumatic brain injuries, frequently heal with excessive callus and faster than normal. Few studies, however, have reported these phenomena being induced by spinal cord injury (SCI). Our objective is to compare the extent of callus and the rate of healing of long-bone fractures in patients with or without SCI. Subgroup comparisons were performed among the patients with SCI in terms of different levels of SCI. METHODS: The final mean volume of callus formation and the rate of union of nailed fractures of the femur were determined radiologically in 22 femoral fracture patients with SCI (seven cervical, six thoracic, and nine lumbar spine injury) and compared with those in a group of 22 patients with similar types of fractures but without SCI. RESULTS: The final mean callus volume in the fracture/SCI group was significantly higher than the fracture-only group (P < 0.001). The fractures in the fracture/SCI group united in an average time of 22.86 weeks compared with 25.04 weeks in the fracture-only group (P < 0.05). We observed 84.6% (11 of 13) of patients with cervical and thoracic SCI patients with accelerated fracture healing (cervical 6 of 7, thoracic 5 of 6), but only 44.4% (4 of 9) of patients with lumbar SCI appeared to show this phenomenon (P < 0.05). CONCLUSIONS: These results confirm that SCI may be associated with accelerated fracture healing and enhanced callus formation. Furthermore, our study revealed a trend toward enhanced osteogenesis in cervical or thoracic SCI compared with lumbar SCI.

PLXNC1 interference alleviates the inflammatory injury, apoptosis and extracellular matrix degradation of IL-1ß-exposed chondrocytes via suppressing GRP78 expression.

BACKGROUND: Osteoarthritis (OA) is a frequently encountered debilitating joint disorder. Whether plexin C1 (PLXNC1) is implicated in OA is far from being investigated despite its well-documented pro-inflammatory property in human diseases. The goal of this study is to expound the specific role of PLXNC1 in OA and elaborate the probable action mechanism. METHODS: Firstly, PLXNC1 expression in the cartilage tissues of patients with OA was examined with GEO database. In interleukin-1beta (IL-1ß)-induced OA cell model, RT-qPCR and western blotting tested the expression of PLXNC1, glucose-regulating protein 78 (GRP78) and extracellular matrix (ECM) degradation-related factors. Cell viability and inflammation were respectively judged by CCK-8 assay and RT-qPCR. TUNEL and western blotting estimated cell apoptosis. The potential binding between PLXNC1 and GRP78 was corroborated by Co-IP assay. Western blotting also tested the expression of endoplasmic reticulum stress (ERS)-associated proteins. RESULTS: As it turned out, PLXNC1 expression was elevated in the cartilage tissues of patients with OA and IL-1ß-treated chondrocytes. When PLXNC1 was depleted, the viability injury, inflammation, apoptosis and ECM degradation of chondrocytes exposed to IL-1ß were obstructed. Besides, GRP78 bond to PLXNC1 in IL-1ß-treated chondrocytes. The ascending GRP78 expression in the chondrocytes exposed to IL-1ß was depleted after PLXNC1 was silenced. Meanwhile, the impacts of PLXNC1 deficiency on the viability, inflammatory response, apoptosis, ECM degradation as well as ERS in IL-1ß-exposed chondrocytes were abolished by GRP78 up-regulation. CONCLUSION: In summary, PLXNC1 silencing might interact with and down-regulate GRP78 to mitigate the apoptosis, inflammation, and ECM degradation of IL-1ß-insulted chondrocytes in OA.

Elevated leptin expression in rat model of traumatic spinal cord injury and femoral fracture.

BACKGROUND: Few studies have reported a relationship between leptin induced by spinal cord injury (SCI) and healing bone tissue. OBJECTIVE: To observe serum and callus leptin expression within the setting of fracture and traumatic SCI. METHODS: Seventy-two male Sprague Dawley rats were randomized equally into four groups: control, SCI group, fracture group, and fracture/SCI group. Rats were sacrificed at 7, 14, 21, and 28 days post-fracture/SCI. Serum leptin was detected using radioimmunoassay at 1, 7, 14, 21, and 28 days, and callus formation was measured radiologically at 14, 21, and 28 days. Callus leptin was analyzed by means of immunohistochemistry. RESULTS: Serum leptin in the fracture group, SCI group, and combined fracture/SCI group were all significantly increased compared to control group at the 1, 7, 14, and 2-day time points (P < 0.05). Serum leptin in the combined fracture/SCI group was significantly higher than in the fracture group at 7, 14, and 21 days (P < 0.05), and higher than in SCI groups at 14 and 21days after operation (P < 0.05). The percentage of leptin-positive cells in the fracture/SCI callus, and callus volume was significantly higher than in the fracture-only group (P < 0.001). CONCLUSIONS: Overall, elevated leptin expression was demonstrated within healing bone especially in the 21 days of a rat model combining fracture and SCI. A close association exists between leptin levels and the degree of callus formation in fractures.

Effect of leptin on bone metabolism in rat model of traumatic brain injury and femoral fracture.

OBJECTIVE: To observe serum and callus leptin expression within the setting of fracture and traumatic brain injury (TBI). METHODS: A total of 64 male SD rats were randomized equally into 4 groups: nonoperated group, TBI group, fracture group, and fracture+TBI group. Rats were sacrificed at 2, 4, 8 and 12 weeks after fracture+TBI. Serum leptin was detected using radioimmunoassay, and callus formation was measured radiologically. Callus leptin was analyzed by immunohistochemistry. RESULTS: Serum leptin levels in the fracture group, TBI group and combined fracture+TBI group were all significantly increased compared with control group at the 2 week time-point (P less than 0.05). Serum leptin in the combined fracture +TBI group was significantly higher than that in the fracture and TBI groups at 4 and 8 weeks after injury (P less than 0.05). The percentage of leptin-positive cells in the fracture+TBI callus and callus volume were significantly higher than those in the fracture-only group (P less than 0.01). CONCLUSIONS: We demonstrated elevated leptin expression within healing bone especially in the first 8 weeks in a rat model of fracture and TBI. A close association exists between leptin levels and the degree of callus formation in fractures.

Biomaterial-supported MSC transplantation enhances cell-cell communication for spinal cord injury.

The spinal cord is part of the central nervous system (CNS) and serves to connect the brain to the peripheral nervous system and peripheral tissues. The cell types that primarily comprise the spinal cord are neurons and several categories of glia, including astrocytes, oligodendrocytes, and microglia. Ependymal cells and small populations of endogenous stem cells, such as oligodendrocyte progenitor cells, also reside in the spinal cord. Neurons are interconnected in circuits; those that process cutaneous sensory input are mainly located in the dorsal spinal cord, while those involved in proprioception and motor control are predominately located in the ventral spinal cord. Due to the importance of the spinal cord, neurodegenerative disorders and traumatic injuries affecting the spinal cord will lead to motor deficits and loss of sensory inputs.Spinal cord injury (SCI), resulting in paraplegia and tetraplegia as a result of deleterious interconnected mechanisms encompassed by the primary and secondary injury, represents a heterogeneously behavioral and cognitive deficit that remains incurable. Following SCI, various barriers containing the neuroinflammation, neural tissue defect (neurons, microglia, astrocytes, and oligodendrocytes), cavity formation, loss of neuronal circuitry, and function must be overcame. Notably, the pro-inflammatory and anti-inflammatory effects of cell-cell communication networks play critical roles in homeostatic, driving the pathophysiologic and consequent cognitive outcomes. In the spinal cord, astrocytes, oligodendrocytes, and microglia are involved in not only development but also pathology. Glial cells play dual roles (negative vs. positive effects) in these processes. After SCI, detrimental effects usually dominate and significantly retard functional recovery, and curbing these effects is critical for promoting neurological improvement. Indeed, residential innate immune cells (microglia and astrocytes) and infiltrating leukocytes (macrophages and neutrophils), activated by SCI, give rise to full-blown inflammatory cascades. These inflammatory cells release neurotoxins (proinflammatory cytokines and chemokines, free radicals, excitotoxic amino acids, nitric oxide (NO)), all of which partake in axonal and neuronal deficit.Given the various multifaceted obstacles in SCI treatment, a combinatorial therapy of cell transplantation and biomaterial implantation may be addressed in detail here. For the sake of preserving damaged tissue integrity and providing physical support and trophic supply for axon regeneration, MSC transplantation has come to the front stage in therapy for SCI with the constant progress of stem cell engineering. MSC transplantation promotes scaffold integration and regenerative growth potential. Integrating into the implanted scaffold, MSCs influence implant integration by improving the healing process. Conversely, biomaterial scaffolds offer MSCs with a sheltered microenvironment from the surrounding pathological changes, in addition to bridging connection spinal cord stump and offering physical and directional support for axonal regeneration. Besides, Biomaterial scaffolds mimic the extracellular matrix to suppress immune responses.Here, we review the advances in combinatorial biomaterial scaffolds and MSC transplantation approach that targets certain aspects of various intercellular communications in the pathologic process following SCI. Finally, the challenges of biomaterial-supported MSC transplantation and its future direction for neuronal regeneration will be presented.

Strategies for Biomaterial-Based Spinal Cord Injury Repair via the TLR4-NF-κB Signaling Pathway.

The repair and motor functional recovery after spinal cord injury (SCI) has remained a clinical challenge. Injury-induced gliosis and inflammation lead to a physical barrier and an extremely inhibitory microenvironment, which in turn hinders the recovery of SCI. TLR4-NF-κB is a classic implant-related innate immunomodulation signaling pathway and part of numerous biomaterial-based treatment strategies for SCI. Numerous experimental studies have demonstrated that the regulation of TLR4-NF-κB signaling pathway plays an important role in the alleviation of inflammatory responses, the modulation of autophagy, apoptosis and ferroptosis, and the enhancement of anti-oxidative effect post-SCI. An increasing number of novel biomaterials have been fabricated as scaffolds and carriers, loaded with phytochemicals and drugs, to inhibit the progression of SCI through regulation of TLR4-NF-κB. This review summarizes the empirical strategies for the recovery after SCI through individual or composite biomaterials that mediate the TLR4-NF-κB signaling pathway.

The potential roles of circular RNAs as modulators in traumatic spinal cord injury.

Spinal cord injury (SCI) may cause long-term physical impairment and bring a substantial burden to both the individual patient and society. Existing therapeutic approaches for SCI have proven inadequate. This is mainly owing to the incomplete understanding of the cellular and molecular events post-injury. Circular RNAs (circRNAs) represent a new class of non-coding RNAs with a covalently closed annular structure that participates in regulating the transcription of certain genes and are linked to various biological processes and diseases. Mounting evidence is indicative that circRNAs are highly expressed in the spinal cord and they play key roles in multiple processes of neurological diseases. Recently, a role for circRNAs as effectors of SCI has emerged, leading to the continuity of relevant research. In this review, we presented current studies with regards to the abnormality of circRNAs mediating SCI by affecting mechanisms of autophagy, apoptosis, inflammation, and neural regeneration. Furthermore, the potential clinical value of circRNAs as therapeutic targets of SCI was also analyzed.

Classification and Treatment Strategies of Concomitant Fibular Column Injuries in Tibial Plateau Fractures.

BACKGROUND: About 1/3 of tibial plateau fractures are associated with proximal fibula fractures, but most proximal fibula fractures are often ignored. The aim of this study was to precisely explain the classification and treatment strategies of six injury types of the fibular column associated with tibial plateau fractures. METHODS: Patients with ipsilateral proximal fibula and tibial plateau fractures treated in our hospital were retrospectively reviewed from Aug 2007 to Mar 2020. Two experienced surgeons and two radiologists divided fibular column injury into 6 injury types according to the AO classification and four-column nine-segment classification. The treatment scheme (surgically treated or conservatively treated) was also recorded. RESULTS: In total, 355 proximal fibula fractures were included. Type 2 fibular head fracture was the most common type of injury in 122, and the segregate of superior tibiofibular syndesmosis was the rarest type in 3. In avulsion injury proximal of fibular pattern, the proportion of patients who need surgical intervention is the highest. CONCLUSIONS: Six injury types in the four-column nine-segment classification covered all types of bony and soft tissue injuries of the fibular column and concisely explained the injury mechanism. The classification is helpful for the precise judgement and decision-making of the concomitant fibular column injuries in tibial plateau fractures.

3D mapping and classification of tibial plateau fractures.

AIMS: Tibial plateau fractures (TPFs) are complex injuries around the knee caused by high- or low-energy trauma. In the present study, we aimed to define the distribution and frequency of TPF lines using a 3D mapping technique and analyze the rationalization of divisions employed by frequently used classifications. METHODS: In total, 759 adult patients with 766 affected knees were retrospectively reviewed. The TPF fragments on CT were multiplanar reconstructed, and virtually reduced to match a 3D model of the proximal tibia. 3D heat mapping was subsequently created by graphically superimposing all fracture lines onto a tibia template. RESULTS: The cohort included 405 (53.4%) cases with left knee injuries, 347 (45.7%) cases with right knee injuries, and seven (0.9%) cases with bilateral injuries. On mapping, the hot zones of the fracture lines were mainly concentrated around the anterior cruciate ligament insertion, posterior cruciate ligament insertion, and the inner part of the lateral condyle that extended to the junctional zone between Gerdy's tubercle and the tibial tubercle. Moreover, the cold zones were scattered in the posteromedial fragment, superior tibiofibular syndesmosis, Gerdy's tubercle, and tibial tubercle. TPFs with different Orthopaedic Trauma Association/AO Foundation (OTA/AO) subtypes showed peculiar characteristics. CONCLUSION: TPFs occurred more frequently in the lateral and intermedial column than in the medial column. Fracture lines of tibial plateau occur frequently in the transition zone with marked changes in cortical thickness. According to 3D mapping, the four-column and nine-segment classification had a high degree of matching as compared to the frequently used classifications.Cite this article: Bone Joint Res 2020;9(6):258-267.

Hyaluronic acid-based hydrogels with tobacco mosaic virus containing cell adhesive peptide induce bone repair in normal and osteoporotic rats.

Tobacco mosaic virus (TMV) has been studied as a multi-functional agent for bone tissue engineering. An osteo-inductive effect of wild-type TMV has been reported, as it can significantly enhance the bone differentiation potential of bone marrow stromal cells both on a two-dimensional substrate and in a three-dimensional (3D) hydrogel system. A TMV mutant (TMV-RGD1) was created which featured the adhesion peptide arginyl-glycyl-aspartic acid (RGD), the most common peptide motif responsible for cell adhesion to the extracellular matrix, on the surface of the virus particle to enhance the bio-functionality of the scaffold material. We hypothesised that the incorporation of either wild-type TMV or TMV-RGD1 in the 3D hydrogel scaffold would induce bone healing in critical size defects of the cranial segmental bone. We have previously tested the virus-functionalised scaffolds, in vitro, with a hyaluronic acid-based system as an in-situ hydrogel platform for 3D cell encapsulation, culture, and differentiation. The results of these experiments suggested the potential of the virus-functionalised hydrogel to promote in vitro stem cell differentiation. The hydrogel-forming system we employed was shown to be safe and biocompatible in vivo. Here, we further explored the physiological responses regarding bone regeneration of a calvarial defect in both normal and osteoporotic ovariectomized rat models. Our results, based on histological analysis in both animal models, suggested that both wild-type TMV and TMV-RGD1 functionalised hydrogels could accelerate bone regeneration, without systemic toxicity, evaluated by blood counts. New bone formation was intensified by the incorporation of the RGD-mutant viral particles. This finding increased the potential for use of the rod-shaped plant virus as a platform for the addition of powerful biofunctionality for tissue engineering applications. This study was approved by the Ethics Committee on Animal Use of the Zhenjiang Affiliated First People's Hospital affiliated to Jiangsu University.

Clinical Efficacy of Different Bone Cement Distribution Patterns in Percutaneous Kyphoplasty: A Retrospective Study.

BACKGROUND: Bone cement distribution patterns in percutaneous kyphoplasty (PKP) is the key factor in keeping the vertebral stabilization and curative effect. However, the same cement volume can result in different bone cement distribution patterns and can thereby lead to different clinical outcomes. Therefore we investigated associations between cement distribution patterns and the occurrence rates of recompression in cemented vertebrae after PKP for patients with osteoporotic vertebral compression fractures (OVCFs). OBJECTIVES: The study focuses attention on the influence of compact and dispersive cement distribution patterns in PKP for patients with OVCFs. STUDY DESIGN: A retrospective cohort study. SETTING: An affiliated people's hospital of a university. METHODS: According to different cement distribution patterns, patients were assigned to 4 groups. The demographic data, radiographic data, and clinical outcomes were compared between the 4 groups. The Visual Analog Scale (VAS) and Oswestry Disability Index (ODI) were evaluated before and 2 days after PKP. Moreover, the relationships between bone cement and clinical outcomes were analyzed. The epidemiologic data, clinical outcomes, and complications of the 4 groups were assessed. Comparisons of the radiologic and clinical results of the 4 groups were made pre- and postoperatively. Anterior height of fractured vertebrae (AH), the kyphotic Cobb angle, and the volumetric cubage index of the fractured vertebrae were measured. RESULTS: A total of 104 subjects were retrospectively analyzed and followed up (median age, 75.01 ± 8.42 years; age range, 56-94 years). The mean procedure duration was 61.26 ± 23.05 minutes (range, 30-140 minutes). The mean follow-up was 12.1 ± 2.2 months (range, 2-15 months). Statistically, there was no significant difference in terms of gender, age, body mass index, and bone mineral density (P > 0.05). The incidence of cement leakage was significantly lower in group A than those in the other groups. The total amount of bone cement injected into 104 cases (104 vertebral bodies in total) was 848.5 mL, and the amount of bone cement injected into a single vertebral body was 7.94 ± 1.38 mL. The amount of bone cement injection in each group was the lowest (6.80 ± 1.66 mL) in group D, followed by (7.94 ± 1.38 mL) group B, and the highest (8.96 ± 1.68 mL) in group A, with a statistically significant difference between the 4 groups (P < 0.05). No serious complications were observed during the follow-up periods. The AH and Cobb angle improved significantly for the 4 groups (P < 0.05). The VAS score decreased from 3.55 ± 0.54, 3.53 ± 0.65, 3.40 ± 0.58, and 3.40 ± 0.66 preoperatively to 0.18 ± 0.39, 0.23 ± 0.41, 0.20 ± 0.40, and 0.15 ± 0.36 at 48 hours postoperatively. The ODI score dropped from 35.65 ± 4.54, 36.45 ± 4.72, 34.12 ± 4.86, and 35.65 ± 4.34 preoperatively to 15.47 ± 1.32, 15.32 ± 1.34, 15.23 ± 1.26, and 15.73 ± 1.17 at 48 hours postoperatively. LIMITATIONS: Our estimation of the vertebral body volume is imprecise. In addition, the number of subjects with OVCFs was small in this retrospective study. The volume of the fractured vertebra was not calculated accurately. CONCLUSIONS: Significant associations between cement distribution patterns and bone cement leakage affected the clinical outcome in patients after PKP. A higher incidence of bone cement leakage was observed in patients with treated vertebrae exhibiting a single-dispersive or single-compact pattern. KEY WORDS: Percutaneous kyphoplasty, osteoporotic vertebral compression fracture, bone cement distribution patterns.

Clinical Efficacy and Rehabilitation of Microscopic "Over the Top" for Bilateral Decompression in Degenerative Lumbar Stenosis: A Retrospective Study.

BACKGROUND: Recently, "over the top" (also called ULBD; microscopic unilateral laminotomy for bilateral decompression) is a less invasive technique for symptomatic degenerative lumbar spinal stenosis (LSS), and this minimally invasive surgical technique has demonstrated favorable therapeutic outcomes. However, the risk of postoperative complications remains controversial. OBJECTIVE: This study is aimed at determining the clinical efficacy and complication and rehabilitation of the microscopic "over the top" for degenerative LSS in geriatric patients. Study Design. This was a retrospective study. Setting. All data were obtained from the People's Hospital of a University. METHODS: A retrospective analysis of 39 consecutive elderly patients treated for LSS by microscopic "over the top" between January 2016 and January 2018 was performed. A postoperative rehabilitation program for geriatric patients with restricted weight-bearing was instituted after the microscopic "over the top" treatment. Estimated blood loss, duration of operation, length of hospitalization, and total complications were also evaluated. The CT and MRI examinations of the lumbar spine were collected to evaluate the completeness of the nerve decompression. Clinical data were assessed at 6 months and 12 months after operation utilizing the visual analog scale (VAS), Oswestry Disability Index (ODI), and 36-Item Short-Form Health Survey (SF-36). Preoperative comorbidities, complications, and revision surgery were also recorded. RESULTS: We enrolled a total of 39 degenerative LSS patients (27 male and 12 female patients, mean age of 75.8 ± 9.2 years). Twenty patients had one-level of degenerative LSS; thirteen patients had two-level of LSS; six patients had three-level of LSS. The average follow-up time in our study was 14.6 ± 7.8 months (range, 6-24 months). The overall complication rate was 10.2% (4/39), and the reoperation rates at one year were 2.5% (1/39). VAS back and leg pain score at 6 months were decreased to 1.8 ± 0.7 and 1.4 ± 0.6, respectively, and remained at 1.9 ± 0.3 and 1.2 ± 0.2 at 12 months, respectively. ODI scores improved significantly from 32.26 ± 6.82 to 11.44 ± 2.50 at 6 months and 10.56 ± 2.29 at 12 months. 36-Item Short-Form Health Survey scores revealed a significant improvement throughout follow-up. Postoperative complications included dural tear (n = 2), neurologic deficit (n = 1), and reoperation (n = 1). No infections or hematomas were reported. Limitation. Multicenter research is recommended to confirm our results and investigate the factors related to clinical and radiographic results. CONCLUSIONS: Microscopic "over the top" technique is a safe, effective option in the therapy of degenerative LSS and obtained satisfactory functional outcomes when coupled with aggressive rehabilitation, with a long recurrence-free recovery.

Effects of antisense oligodeoxynucleotide to type I collagen gene on hypertrophic scars in the transplanted nude mouse model.

BACKGROUND: Antisense nucleic acids are effective in inhibiting harmful or uncontrolled gene expression. We had previously proved that the antisense DNA to type I collagen could effectively inhibit the synthesis of collagen type I in cultured hypertrophic scar fibroblasts, suggesting a potential role in anti-scarring, but there are no published reports of its effect on scar in the transplanted nude mouse model. AIMS: To investigate the effects of antisense oligodeoxynucleotide (ASODN) to type I collagen gene on hypertrophic scars in the transplanted nude mouse model and clarify the potential of ASODN for the treatment of scars. METHODS: The nudemousemodel of hypertrophic scar was created and subjected to daily injections with ASODN and LipofectamineTM for 2 ,4 or 6 weeks.We then examined the scars for changes in histopathological characteristics. The effects of ASODNon type I collagen gene expression were examined by reverse transcription-polymerase chain reaction and Western blots. RESULTS: The ASODN could remarkably alleviate the scar in the nude mouse model and consistently inhibit type I collagen gene expression at both the mRNA and protein levels. CONCLUSION: ASODN was effective in downregulating type I collagen gene expression and could prove to be useful in the treatment of scars.

Enhanced Bone Defect Repair by Polymeric Substitute Fillers of MultiArm Polyethylene Glycol-Crosslinked Hyaluronic Acid Hydrogels.

Bone regeneration is still one of the greatest challenges for the treatment of bone defects since no current clinical approach has been proven effective. To develop an alternative biodegradable bone graft material, multiarm polyethylene glycol (PEG) crosslinked hyaluronic acid (HA) hydrogels are synthesized and applied to promote osteogenesis of mesenchymal stem cells (MSCs) with the ultimate goal for bone defect repair. The multiarm PEG-HA hydrogels provide a significant improvement of alkaline phosphatase (ALP) activity and calcium mineralization of the in vitro encapsulated MSCs under osteogenic condition after 3, 7, and 28 days. In addition, the multiarm PEG-HA hydrogels also facilitate healing of the cranial bone defects more effectively in a Sprague Dawley rat model after 10 weeks of implantation based on histological evaluations and microcomputed tomography analysis. These promising results set the stage for the development of innovative biodegradable hydrogels to provide a more effective and versatile treatment option for bone regeneration.

Using Plant Virus Based Nanorods to Modulate the Differentiation of Human Bone Marrow Stem Cells.

Tobacco mosaic virus (TMV) is a protypical nanorod-shaped bioparticles that has been used as a building block to construct a variety of self-assembled nanomaterials for different biomedical applications, including drug delivery, in vivo imaging, tumor immunotherapy and tissue engineering. In this work, the roles of TMV and its mutant TMV-RGD1 nanoparticles on the differentiation of human bone marrow stem cells (hBMSCs), an important process in bone regeneration, were carefully investigated. We observed that cells cultured on the TMV-RGD1 nanorods coated substrate showed significantly higher levels of gene and protein expression of osteo-specific markers osteocalcin (OCN) and bone morphogenetic protein 2 (BMP2). Investigation of alkaline phosphatase (ALP) activity and calcium deposition further confirmed that the TMV-RGD1 substrate could promote the osteogenesis and induce the mineralization of hBMSCs. On the other hand, the adipogenesis was downregulated on TMV and TMV-RGD1 coated substrates. Taken together, this study demonstrates for the first time the potential of TMV-RGD1 in promoting osteogenic differentiation of hBMSCs which can lead to future applications in clinical bone engineering.

C7 slope and its association with serum lipid levels and Modic changes in patients with cervical spondylotic myelopathy.

Background: Several studies have substituted the T1 slope (T1S) with the C7 slope (C7S) because the C7 endplate is clearer on radiographs. Further, abnormal serum lipid levels have been proven to be related with the development of disc degeneration. The aim of this study was to explore the relationship between C7S, serum lipid levels, cervical parameters related to cervical sagittal balance and Modic changes (MCs) in patients with multisegment cervical spondylotic myelopathy (CSM). Methods: Between January 2014 and January 2017, 75 patients with multisegment CSM were enrolled in our retrospective study. Gender, age, history of smoking status and alcohol consumption, and laboratory test data were recorded. The cervical sagittal balance parameters C7S, T1S, cervical lordosis (CL), neck tilt (NT), thoracic inlet angle (TIA), C2-C7 sagittal vertical axis (SVA), and T1S-CL were analyzed with Spearman correlation tests and multiple linear regression analysis. We diagnosed MCs through computed tomography or magnetic resonance imaging of the cervical spine. Patients were divided into four subgroups according to the presence or absence of MCs and their C7S values. Results: 75 patients were included in our study. Age, gender, C7S, and T1S were significantly different between the two groups. However, there was no statistical difference with regard to smoking status, alcohol consumption, lipoprotein(a), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, albumin, globulin, triglycerides, total cholesterol, Ca2+, CL, T1S, TIA, NT, and T1S-CL. The correlation between HDL-C, LDL-C, ALB, GLB, Ca2+, C7S, T1S, MCs, NT, TIA, and C2-C7 SVA was statistically significant. Conclusion: Significant correlations were observed between MCs and TG (as well as other preoperative sagittal parameters), which may accelerate the development of degeneration of the cervical spine. Therefore, alcohol consumption, TG, and sagittal parameters, such as C7S, and T1S could be a promising candidate for the assessment of cervical sagittal balance and predicting neck pain.