Co-overexpression of OPN, IGF-1 and CNTF augment the therapeutic effect of DPSC on spinal cord injury.

Background aims: Spinal cord injury (SCI) is one of the most complex and destructive diseases of the nervous system, which can lead to permanent loss of tactile perception. But existing treatment methods have limited effects. To establish a novel method that may be therapeutic in repairing the injured spinal cord, gene-modified dental pulp stem cells (DPSCs) were injected in situ. Methods: Adenovirus carrying osteopontin (OPN), Insulin-like growth factor 1 (IGF-1) and cailiary-derived neurotrophic factor (CNTF) (Ad-OIC) was constructed. After modified with Ad-OIC, supernatant of DPSC were co-cultured with HT-22 cells and the effect of DPSC-OIC on the HT-22 cells were evaluated via Cell Counting Kit-8 (CCK-8) assay, Real-Time polymerase chain reaction (PCR) analysis, laser confocal microscopy and fluorescence activating cell sorter (FACS). DPSC-OIC were injected in the lesion area of injured spinal cord and the survival time of transplanted cells were measured by bioluminescence imaging system. The recovery of the injured spinal cord was evaluated by behavioral score, radiological evaluation and immunopathological analysis. Results: DPSC-OIC could enhance the proliferation and axon growth of HT-22 cells, and protect HT-22 cells from H2O2 induced apoptosis. The transplanted DPSC-Null or DPSC-OIC could survive for more than two weeks in local injection site. DPSC-OIC treatment could increase Basso-Mouse Scale (BMS) scores, improve Magnetic Resonance Imaging (MRI) manifestation and promote bladder function recovery. Less apoptotic neurons and more proliferative cells were found in the lesion area of DPSC-OIC treated spinal cord. Nestin+ cells and neural stem cell marker (Sox2) were both up-regulated after DPSC-OIC treatment. Additionally, inhibitory extracellular matrix proteoglycan Neural/Glial Antigen 2 (NG2) was down-regulated and axon growth promotive factor fibronectin was up-regulated after both DPSC-Null (DPSCs infected with Ad-Null) and DPSC-OIC treatments. Conclusions: DPSC-OIC could be a novel effective method for treating SCI.

Periostin-targeted SDSSD peptide decorated calcium phosphate nanocomposites incorporation with simvastatin for osteoporosis treatment.

The limited options of anabolic drugs restrict their application potential in osteoporosis treatment, despite their theoretical superiority in therapeutic efficacy over antiresorptive drugs. As a prevailing strategy, nano-delivery systems could offer a wider choice of anabolic drugs. In this study, calcium phosphate nanocomposites incorporated with simvastatin (Sim) with periostin-targeting ability were designed and prepared for osteoporosis treatment. Carboxymethyl dextran (CMD) as an anionic and hydrophilic dextran derivative was used to stabilize CaP. In addition, periosteum-targeted peptide (SDSSD) was further grafted on CMD to achieve the bone targeting function. In a one-step coordination assembly strategy, hydrophobic anabolic agent Sim and SDSSD-CMD graft (SDSSD-CMD) were incorporated into the CaP nanoparticles forming SDSSD@CaP/Sim nanocomposites. The resulting SDSSD@CaP/Sim possesses uniform size, great short-term stability and excellent biocompatibility. Moreover, SDSSD@CaP/Sim exhibited a reduced release rate of Sim and showed slow-release behaviour. As anticipated, the nanocomposites exhibited bone bonding capacity in both cellular and animal studies. Besides, SDSSD@CaP/Sim achieved obviously enhanced osteoporosis treatment effect compared to direct injection of Simin vivo. Therefore, our findings highlight the potential of SDSSD-incorporated and CaP-based nanocomposites as a viable strategy to enhance the therapeutic efficacy of anabolic drugs for osteoporosis treatment.

Mid-term low back pain improvement after total hip arthroplasty in 306 patients with developmental dysplasia of the hip.

BACKGROUND: Low back pain (LBP) from hip and spinal disorders has been one of the main reasons for visiting physicians in patients with developmental dysplasia of the hip (DDH). It is essential to identify the LBP improvement among all grades of DDH patients treated with total hip arthroplasty (THA) at 5-year follow-up. METHODS: The study included 407 hips of 306 patients (38 males, 268 females) who underwent THA between July 2007 and December 2016. There were 65 hips in Crowe I, 61 hips in Crowe II, 69 hips in Crowe III, and 212 hips in Crowe IV. One hundred and fourteen hips received subtrochanteric shortening. Patients included 101 bilateral THA (BTHA) and 205 unilateral THA (UTHA). The evaluation was performed through Back Pain Function Scale (BPFS), Harris hip score, Visual Analogue Scale (VAS), operative data and radiographic examinations. RESULTS: The BPFS in patients of unilateral Crowe III and IV relieved significantly more (p < 0.05). However, the BPFS in patients with bilateral symmetry DDH hips relieved significantly less than other groups of DDH hips (p < 0.05). Harris in hips of Crowe II improved significantly more (p < 0.05). The VAS in hips of Crowe II and III improved significantly more (p < 0.05). The unilateral THA surgical time, blood loss, blood transfusion, and osteotomy number and length in Crowe IV were significantly more (p < 0.05). CONCLUSION: THA is reliable to relieve LBP in DDH patients of unilateral Crowe III and IV; however, in patients with unilateral Crowe I, Crowe II, and bilateral DDH hips, the LBP improvements were limited. This should assist shared decision-making between orthopedic surgeons and patients. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

Hydroxytyrosol Ameliorates Intervertebral Disc Degeneration and Neuropathic Pain by Reducing Oxidative Stress and Inflammation.

Low back pain (LBP) seriously affects human quality of life. Intervertebral disc degeneration (IVDD) is the main pathological factor that leads to LBP, but the pathological mechanism underlying IVDD has not been fully elucidated. Neuropathic pain caused by IVDD is an important pathological factor affecting people's daily lives. Therefore, it is very important to identify therapeutic drugs to ameliorate IVDD and secondary neuropathic pain. Hydroxytyrosol (HT) is a natural compound derived from olive leaves and oil and has anti-inflammatory, antioxidant, and antitumor activities and other properties. In this study, TNF-α-stimulated human nucleus pulposus cells (HNPCs) were used to simulate the local inflammatory microenvironment observed in IVDD in vitro to explore the role of HT in alleviating various pathological processes associated with IVDD. A rat needle puncture model was used to further explore the role of HT in alleviating IVDD. Lipopolysaccharide (LPS) was used to stimulate microglia in vitro to comprehensively explore the role of HT in alleviating neuropathic pain, and a rat model involving chronic compression of the dorsal root ganglion (CCD) was established to simulate the neuropathic pain caused by IVDD. This study suggests that HT reduces the expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome, a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4) and matrix metalloproteinase-13 (MMP-13); inhibits the production of mitochondrial reactive oxygen species (ROS); and maintains mitochondrial homeostasis. Thus, HT appears to reduce the rate of apoptosis and mitigate the loss of major intervertebral disc components by inhibiting the nuclear factor kappa-B (NF-κB) signaling pathway. Moreover, HT inhibited the secretion of COX-2, tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-1ß, and iNOS and activation of the NLRP3 inflammasome in microglia by inhibiting the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) and extracellular regulated protein kinase (ERK) signaling pathways. In conclusion, HT plays a protective role against IVDD and secondary neuropathic pain by inhibiting the NF-κB, PI3K/AKT, and ERK signaling pathways.

Are Both Preoperative Full-Spine 3Dimensional Computed Tomography Scans and X-Ray Films Necessary for Patients with Ankylosing Spondylitis Kyphosis?

OBJECTIVE: This study is aimed to investigate whether both pre-operative full-spine 3Dimensional computed tomography scan (3D CT) and X-ray film were necessary for patients with severe ankylosing spondylitis (AS) kyphosis deformity. METHODS: The research objects were selected from the inpatients with AS in our hospital from 2017 to 2019. A total of 42 patients were included in the study. On both the synthesized 2Dimensional (2D) lateral radiograph and X-ray film, the globe kyphosis (GK), the lumber lordosis (LL), the thoracolumbar kyphosis (TLK) and the thoracic kyphosis (TK) were measured. And the angle seventh thoracic vertebra (T7), the angle twelfth thoracic vertebra (T12) and the angle third lumber vertebra (L3) were also measured. Two researchers with professional medical education were randomly selected to perform the measurement method and record the measurement data. Two researchers independently completed, recorded, and evaluated the accuracy and consistency of the measurement data. This study used intraclass correlation coefficient (ICC) to analyze the synthesized 2D lateral radiograph and general X-ray film of 42 subjects by two researchers, in order to evaluate the consistency of data measurement results between the examiners. Through the comparison of the above parameters that the GK, LL, TLK, TK, angle T7, angle T12 and angle L3, the evaluation was made both pre-operative full-spine 3D CT and X-ray film were necessary for patients with severe AS kyphosis deformity. RESULTS: There was no significant difference between the GK, LL, TLK, TK, angle T7, angle T12, angle L3 on the synthesized 2D lateral radiograph and that on X-ray film (P = 0.240, 0.324, 0.199, 0.095, 0.421, 0.087, 0.478). Agreement two researchers was excellent with ICC of the GK, LL, TLK, TK, angle T7, angle T12, angle L3 (0.977, 0.969, 0.986, 0.945, 0.947, 0.915, 0.857) on the synthesized 2D lateral radiograph. The Bland-Altman plot results that the measurement results of examiners are reliable and stable. CONCLUSION: By estimating the degree of spinal sagittal imbalance and measuring the Cobb angle, we can see that full-length spine radiographs of the patients are unnecessary for patients with severe AS kyphosis deformity who will or have undergone preoperative spine 3D CT.

Clinical Results of Utilizing the Satellite Rod Technique in Treating Ankylosing Spondylitis Kyphosis.

OBJECTIVE: According to the literature, there are no clinical reports documenting the use of the satellite rod technique in the treatment of ankylosing spondylitis kyphosis. The purpose of this retrospective study was to compare the clinical outcome of patients with ankylosing spondylitis kyphosis who adopted satellite rods versus those who did not. METHODS: Patients with ankylosing spondylitis kyphosis who underwent one or two-level pedicle subtraction osteotomy (PSO) were reviewed, and total of 119 patients (112 males and seven females, average age 39.89 ± 6.61 years) were eligible and included in this present study. Anterior-posterior and lateral full-length spine X-ray films were performed preoperatively and at the two-year follow-up visit. Global kyphosis (GK), lumbar lordosis (LL), thoracolumbar kyphosis (TLK), thoracic kyphosis (TK), and osteotomy angle (OA) were measured. The complications of every group of patients were collected. Pre- and postoperative health-related quality of life instruments, including the Bath Ankylosing Spondylitis Functional Index (Basfi) and Scoliosis Research Society outcomes instrument-22 (SRS-22), were recorded. The patients were divided into three groups based on features of their osteotomy including PSO levels and whether the satellite rod technique was applied. Patients who underwent one-level PSO without the satellite rod technique were categorized in the one-level group. Patients who underwent one-level PSO with the satellite rod technique were classified in the satellite rod group. Patients who underwent two-level PSO without the satellite rod technique were included in the two-level group. The paired sample t test was used to compare pre- and postoperative parameters. One-way ANOVA was performed for multiple group comparisons. RESULTS: The average follow-up time is 29.31 ± 3.66 months. The patients' GK were significantly improved from 46.84 ± 20.37 degree to 3.31 ± 15.09 degree. OS achieved through each osteotomy segment of one-level group (39.78 ± 12.29 degree) and satellite rods group (42.23 ± 9.82 degree), was larger than that of two-level group (34.73 ± 7.54 and 28.85 ± 7.26 degree). There was no significant difference between the one-level group and the satellite rod group in achieving the OS. Thirteen patients experienced different complications (10.92%). Three patients experienced rod fracture in the one-level group. There was no rod fracture or screw failure in the satellite rod group or the two-level group. CONCLUSION: The satellite rod technique is also recommended for patients who undergo PSO osteotomy to correct ankylosing spondylitis kyphosis deformities.

A Comparison Between Retaining and Resecting the Posterior Longitudinal Ligament in Percutaneous Endoscopic Transforaminal Discectomy for Disc Herniation: A Retrospective Cohort Study.

OBJECTIVE: To compare the efficacy and safety of retaining the posterior longitudinal ligament (PLL) with resecting the PLL in inside-out percutaneous endoscopic transforaminal discectomy (PETD) surgery for lumbar disc herniation (LDH). METHOD: A total of 135 patients with symptomatic LDH who were treated by inside-out PETD surgery from January 2015 to January 2017were included in this retrospective analysis. There were 38 males and 30 females in the PLL resection group (mean age = 52.40 ± 8.73 years) and 35 males and 32 females in the PLL retention group (mean age = 53.50 ± 9.24 years). The visual analogue scale (VAS) score, Oswestry disability index (ODI), and modified MacNab criteria were used to evaluate clinical outcomes. Operation time, blood loss, recurrence of LDH, and complications were recorded. Three months after surgery, magnetic resonance imaging was performed to confirm that nerve root compression was relieved. RESULTS: The VAS and ODI scores improved significantly immediately after surgery, at 1 month after surgery, at 3 months after surgery, and at last follow-up compared with those before surgery (P < 0.01). The scores also improved significantly between immediately after surgery and 1 month after surgery in the two groups (P < 0.001). Multivariate analysis indicated that age ≥ 50 years (odds ratio (OR) = 6.33, 95% confidence interval (CI): 1.64-21.98, P = 0.014), pain duration ≥6 months (OR = 4.68, 95% CI: 1.29-6.51, P = 0.025), pre-ODI score ≥ 40% (OR = 5.97, 95% CI: 2.41-14.86, P = 0.003) were all associated with poor functional outcomes. There was no significant difference in the excellent/good ratio between the two groups and the mean operation time of the retention group was 71.5% of that of the resection group (82.7 ± 18.5 min vs 115.6 ± 24.6 min, P < 0.01). In the patients, no serious complications, such as dural tear, wound infection, or persistent nerve root injury, were observed during the follow-up period. There was no significant difference in the complication rate between the two groups (6/68 vs 6/67, P = 0.979). Although the recurrence rate was higher in retention group, there was no significant difference between the two groups (1/68 vs 2/67, P = 0.551). CONCLUSION: The PLL is recommended to be retained for inside-out PETD surgery.

Dental pulp stem cell-derived exosomes suppress M1 macrophage polarization through the ROS-MAPK-NFκB P65 signaling pathway after spinal cord injury.

Stem cell-derived exosomes have recently been regarded as potential drugs for treating spinal cord injury (SCI) by reducing reactive oxygen species (ROS) and suppressing M1 macrophage polarization. However, the roles of ROS and exosomes in the process of M1 macrophage polarization are not known. Herein, we demonstrated that ROS can induce M1 macrophage polarization and have a concentration-dependent effect. ROS can induce M1 macrophage polarization through the MAPK-NFκB P65 signaling pathway. Dental pulp stem cell (DPSC)-derived exosomes can reduce macrophage M1 polarization through the ROS-MAPK-NFκB P65 signaling pathway in treating SCI. This study suggested that DPSC-derived exosomes might be a potential drug for treating SCI. Disruption of the cycle between ROS and M1 macrophage polarization might also be a potential effective treatment by reducing secondary damage.

Hematopoietic cell kinase enhances osteosarcoma development via the MEK/ERK pathway.

Osteosarcoma (OS) is a sarcoma with high rates of pulmonary metastases and mortality. The mechanisms underlying tumour generation and development in OS are not well-understood. Haematopoietic cell kinase (HCK), a vital member of the Src family of kinase proteins, plays crucial roles in cancer progression and may act as an anticancer target; however, the mechanism by which HCK enhances OS development remains unexplored. Therefore, we investigated the role of HCK in OS development in vitro and in vivo. Downregulation of HCK attenuated OS cell proliferation, migration and invasion and increased OS cell apoptosis, whereas overexpression of HCK enhanced these processes. Mechanistically, HCK expression enhanced OS tumorigenesis via the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway; HCK upregulation increased the phosphorylation of MEK and ERK and promoted epithelial-mesenchymal transition, with a reduction in E-cadherin in vitro. Furthermore, HCK downregulation decreased the tumour volume and weight in mice transplanted with OS cells. In conclusion, HCK plays a crucial role in OS tumorigenesis, progression and metastasis via the MEK/ERK pathway, suggesting that HCK is a potential target for developing treatments for OS.

Isobavachalcone prevents osteoporosis by suppressing activation of ERK and NF-κB pathways and M1 polarization of macrophages.

Estrogen receptors alpha (ERα), a member of the nuclear receptor protein family, was found to play an important role in maintaining bone mass. Its downstream signaling proteins such as ERK and NF-κB were reported to be involved in development of osteoporosis, which meant that targeting ERα might be an effective strategy for searching for new drugs to prevent bone loss. In this study, we demonstrate that isobavachalcone (ISO), as one of bioactive compounds isolated from Psoralea corylifoliaLinn, has high affinity with ERα. The effects of ISO are investigated on receptor activator of NF-κB ligand (RANKL)-induced osteocalstogenesis. It is reported that ISO inhibits the RANKL-mediated increase of osteoclast-related genes MMP9, cathepsink and TRAR in RAW264.7 cells. Moreover, in vitro experiment shows that ISO exhibits an inhibitory effect on ERK and NF-κB signaling pathway, and suppresses RANKL-induced expression of osteoclast-related transcription factors NFATc1 and c-Fos. However, the impact of ISO in these molecules is eliminated by the application of ERα antagonist AZD9496.We further verified pharmacological effects of ISO in ovariectomized osteoporotic mice, and ISO significantly prevented bone loss and decreased M1 polarization of macrophages from marrow and spleen. Collectively, our data suggest that ISO prevents osteoporosis via suppressing activation of ERK and NF-κB signaling pathways as well as M1 polarization of macrophages.

Disordered leptin and ghrelin bioactivity in adolescent idiopathic scoliosis (AIS): a systematic review and meta-analysis.

BACKGROUND: Adolescents with scoliosis consistently demonstrate lower body weight, lean muscle mass, and bone mineral density than healthy adolescent counterparts. Recent studies have focused on understanding how leptin and ghrelin signaling may play a role in adolescent idiopathic scoliosis (AIS). In our current study, we aim to evaluate the serum levels of leptin, soluble leptin receptor (sOB-R), and ghrelin in AIS patients through systematic review and meta-analysis. METHODS: We conducted our systematic review by searching the keywords in online databases including PubMed, Embase, Cochrane, Elsevier, Springer, and Web of Science from the time of database inception to January 2020. Inclusion criteria were studies that measure leptin, soluble leptin receptor (sOB-R), and ghrelin levels in AIS patients. Selection of studies, assessment of study quality, and data extraction were performed by two reviewers independently. Then, data was analyzed to calculate the mean difference and 95% confidence interval (CI). RESULTS: Seven studies concerning leptin/sOB-R and three studies concerning ghrelin were qualified for meta-analysis (one study concerning both leptin and ghrelin). Serum leptin of patients with AIS were significantly lower when compared with healthy controls, with the weighted mean difference (WMD) of - 0.95 (95% CI - 1.43 to - 0.48, p < 0.0001) after reducing the heterogeneity using six studies for meta-analysis, while sOB-R and ghrelin level was significantly higher in AIS group when compared with control group, with the WMD of 2.64 (95% CI 1.60 to 3.67, p < 0.001) and 1.42 (95% CI 0.48 to 2.35, p = 0.003), respectively. CONCLUSION: Our current meta-analysis showed that serum level of leptin in AIS patients was significantly lower when compared with control subjects, while serum sOB-R and ghrelin levels were significantly higher in AIS patients. More clinical studies are still required to further validate the predictive value of leptin or ghrelin for the curve progression for AIS patients.

Improvement of Sleep Quality in Patients With Ankylosing Spondylitis Kyphosis After Corrective Surgery.

STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of this study is to investigate the changes in sleep quality in patients surgically treated for kyphosis due to ankylosing spondylitis (AS) and the correlation between these changes and spinal sagittal realignment. SUMMARY OF BACKGROUND DATA: Sleep problems are prevalent in AS patients. However, little attention has been paid to the sleep quality in patients with AS kyphosis and the effect of surgical intervention on sleep quality. METHODS: We have retrospectively reviewed 62 patients with AS-induced thoracolumbar kyphosis who underwent surgically treatment from October 2012 to November 2016. Sleep quality was evaluated by the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Preoperative and postoperative radiological characteristics and supine function were documented. We compared the above-mentioned parameters pre- and 24 months postoperatively and analyzed the correlation of the changes in the PSQI with the changes in radiological characteristics. RESULTS: Fifity-one patients (82%) classified as poor sleepers preoperatively. In addition to use of sleeping medication, each domain of the PSQI and the total PSQI were increased postoperatively. Improved sleep quality was correlated with changes in spinal sagittal characteristics, among which the lumbar lordosis (LL) and the chin-brow vertical angle (CBVA) were the independent correlation factors. The number of patients with supine dysfunction decreased from 89% to 15% after surgery. Significant differences were identified in the PSQI scores between the patients with and without supine dysfunction either pre- or postoperatively. CONCLUSION: Surgical correction of spinal deformity may improve sleep quality and supine function in patients with AS. Spinal sagittal realignment may be correlated with the improvement of sleep quality. LEVEL OF EVIDENCE: 4.

Compensatory Mechanism of Maintaining the Sagittal Balance in Degenerative Lumbar Scoliosis Patients with Different Pelvic Incidence.

OBJECTIVE: To investigate the compensatory mechanism of maintaining the sagittal balance in degenerative lumbar scoliosis patients with different pelvic incidence (PI). METHODS: This was a retrospective imaging observation study. Patients in our department with degenerative lumbar scoliosis between 2017 and 2019 were reviewed. A total of 36 patients were eligible and included in the present study. The average age of those patients was 64.22 years, including 8 men and 28 women. The coronal and sagittal parameters were measured on full-length spine X-ray film, including globe kyphosis (GK), lumber lordosis (LL), thoracolumbar kyphosis (TLK), thoracic kyphosis (TK), sagittal vertical axis (SVA), sagittal shift angle, Cobb angle, coronal shift angle, and vertebra. The anterior pelvic plane angle (APPA) and pelvic parameters were also measured, including the pelvic tilt (PT), the PI, and the sacral slope (SS). PI-LL, LL-SS, and GK-SS were calculated. Traditional pelvic tilt was also calculated using the following formula: cPT = PI × 0.37-7. These patients were divided into two groups according to their PI values. The patients' PI value in Group 1 was smaller than 50°. The patients' PI value in Group 2 was equal to or larger than 50°. RESULTS: These patients' SS, PT, PI, LL, TLK, TK, and GK were 28.70° ± 11.36°, 23.28° ± 6.55°, 52.00° ± 11.03°, 31.66° ± 14.12°, 12.12° ± 14.9°, 17.81° ± 13.53°, and -13.17° ± 16.27°. The sagittal shift angle, the APPA, the Cobb angle, the coronal shift angle, vertebra, PI-LL, cPT, APPA-4, LL-SS, and GK-SS were 4.38° ± 5.75°, -12.55° ± 8.83°, 30.03° ± 12.59°, 2.40° ± 2.13°, 4.08 ± 0.93, 19.86° ± 10.97°, 12.35° ± 4.55°, -8.30° ± 9.07°, 3.30° ± 8.82°, and 15.53° ± 9.83°, respectively. There was no significant difference between PT and cPT + APPA-4 or between cPT and PT-APPA+4. There was significant difference between PT and cPT + APPA or between cPT and PT-APPA. This demonstrated that the APPA-4 is reliable as degree of the pelvic sagittal retroversion. There were significant differences in SS, PI, LL, TLK, GK, APPA, PT-APPA, PT-APPA+4, cPT, and APPA-4 between Group 1 and Group 2. There were no significant differences in PT, TK, sagittal shift angle, SVA, Cobb angle, coronal shift angle, vertebra number, PI-LL, cPT + APPA, cPT + APPA-4, LL-SS, and GK-SS between Group 1 and Group 2. The Pearson tests showed that PI-LL had significant correlations with TK, LL, sagittal shift angle, SVA, and LL-SS. There was no significant correlation between PI-LL and Cobb angle, GK, TLK, APPA, vertebra, Coronal Shift Angle, or GK-SS. CONCLUSION: The APPA-4 is reliable as degree of the pelvic sagittal retroversion. In degenerative lumbar scoliosis, patients with smaller PI tended to rely more on the pelvic retroversion to maintain the sagittal balance than patients with larger PI, or patients with smaller PI were likely to start up the pelvic retroversion compensatory mechanism earlier than the patients with larger PI.

Hierarchical assembly of dual-responsive biomineralized polydopamine-calcium phosphate nanocomposites for enhancing chemo-photothermal therapy by autophagy inhibition.

The induction of autophagy in cancer cells would occur in response to several therapy strategies, including chemotherapy and photothermal therapy (PTT). Hence, combined autophagy inhibition has been regarded as a prevailing strategy to enhance treatment sensitivity in cancers. Herein, dual pH/thermal responsive biomineralized nanocomposites (PCNPs) were rationally designed and prepared based on the hierarchical assembly of calcium phosphate (CaP) and polydopamine (PDA). The first step in the self-assembly process involves the incorporation of hydrophobic chemotherapeutic docetaxel (DTX) into the CaP nanoparticles. Next, PDA was utilized as the coating to hierarchically self-assemble onto the surface of CaP through a simple self-polymerization of dopamine. Third, the autophagy inhibitor chloroquine (CQ) was absorbed onto the surface of PDA via non-covalent interactions, forming PCNPs/DC. CQ was the only FDA approved autophagy inhibitor in clinical trials that could inhibit autophagosome fusion and degradation. The resulting PCNPs/DC could exhibit dual pH/thermal responsive properties due to the acid-sensitive CaP core and the photothermal effect of the PDA coating. Effective inhibition of autophagy in cancer cells could be realized by blocking the lysosome and weakening the degradation of autolysosomes by PCNPs/DC. Interestingly, complementary autophagy inhibition could therefore sensitize the effects of chemo-photothermal therapy both in vitro and in vivo with negligible toxicity. Therefore, these hierarchically assembled biomineralized nanocomposites would be used as a prevailing strategy to sensitize chemo-photothermal therapy by complementary autophagy inhibition.

Relationship between postoperative lordosis distribution index and adjacent segment disease following L4-S1 posterior lumbar interbody fusion.

BACKGROUND: Adjacent segment disease (ASD) is an acknowledged problem of posterior lumbar interbody fusion (PLIF). Many studies have been reported concerning the role of lordosis distribution index (LDI) in spinal biomechanics. However, few reports have been published about the impact of LDI on ASD following L4-S1 PLIF. METHODS: The study enrolled 200 subjects who underwent L4-S1 PLIF for degenerative spine disease from 2009 to 2014. The average follow-up term was 84 months. Several lower lumbar parameters were measured, including lower lumbar lordosis (LLL), lumbar lordosis (LL), pelvic incidence (PI), and LDI on the pre and postoperative radiograph. Perioperative information, comorbidities, and operative data were documented. Kaplan-Meier curves were plotted for the comparisons of ASD-free survival of 3 different types of postoperative LDI subgroups. RESULTS: The incidence of ASD was found to be 8.5%. LL and LLL increased by 3.96° (38.71° vs 42.67°; P < 0.001) and 3.60° (26.22° vs 28.82°; P < 0.001) after lower lumbar fusion surgery, respectively. Lordosis distribution index (LDI) increased by 0.03 (0.66 vs 0.69, P = 0.004) postoperatively. A significant difference (P = 0.001) was observed when comparing the incidence of ASD among postoperative LDI subgroups. The Kaplan-Meier curves showed a marked difference in ASD-free survival between low and moderate LDI subgroup (log-rank test, P = 0.0012) and high and moderate LDI subgroup (log-rank test, P = 0.0005). CONCLUSION: Patients with abnormal postoperative LDI were statistically more likely to develop ASD than those who had normal postoperative LDI. Moreover, patients with low postoperative LDI were at greater risk for developing ASD than those with high postoperative LDI over time.

Comparison of loss of correction between PSO and VCD technique in treating thoracolumbar kyphosis secondary to ankylosing spondylitis, a minimum 2 years follow-up.

BACKGROUND: Pedicle subtraction osteotomy (PSO) and vertebral column decancellation (VCD) are frequently used methods for correction of thoracolumbar kyphosis resulting from ankylosing spondylitis (AS). However, there are limited reports performed to evaluate the difference of loss of correction and the effectiveness of PSO and VCD techniques in patients with thoracolumbar kyphosis secondary to AS. OBJECTIVE: To retrospectively estimate the effectiveness of correction and loss of correction of PSO and VCD techniques in patients with thoracolumbar kyphosis secondary to AS. METHODS: We performed a retrospective review of 61 consecutive AS kyphosis patients undergoing PSO or VCD surgery from March 2012 to April 2015. The patients were divided into PSO group (n = 25) and VCD group (n = 36) according to the types of osteotomies. Measurement of the radiographic parameters was performed and the change was analyzed. RESULTS: Mean loss of correction in the global kyphosis was 2.31° in the PSO group and 2.29° in VCD group at the last follow-up, respectively, with no significant difference. Progressive junctional kyphosis occurred in both groups. VCD obtained a significantly larger correction than PSO while sharing a similar incidence of complications. No serious complications were observed in the two groups. CONCLUSION: The PSO osteotomy and VCD osteotomy are both safe and effective methods in treating thoracolumbar kyphosis secondary to AS. Mild loss of correction mainly occurred in the global kyphosis in both techniques with no significant difference.

Comparison of 2 Surgeries in Correction of Severe Kyphotic Deformity Caused by Ankylosing Spondylitis: Vertebral Column Decancellation and Pedicle Subtraction Osteotomy.

OBJECTIVE: To compare the treatment results between 1-level vertebral column decancellation (VCD) and pedicle subtraction osteotomy (PSO) for correcting severe kyphotic deformity in ankylosing spondylitis (AS). VCD and PSO have been used to correct AS-related kyphotic deformity, but the differences on correcting results between VCD and PSO are not clear. METHODS: Between 2013 and 2015, 57 patients underwent 1-level spinal osteotomy (VCD: n = 30; PSO: n = 27) for correcting kyphotic deformity. Sagittal parameters, fusion results, surgical information, and clinical outcomes were documented and compared. All data were obtained before and 1 week after surgery, 6 months after surgery, and at final follow-up (at least 2 years). RESULTS: VCD provided significantly greater osteotomy angle (50.8° ± 9.7°) than PSO (38.5° ± 6.1°). In the VCD group, the change of the anterior column was 5.0 ± 1.3 mm, which was larger than the PSO group. The middle column was shortened by 9.9 ± 2.0 mm and 19.1 ± 3.3 mm in the VCD group and PSO group, respectively. There was no significant difference in operating time and blood loss between the 2 groups. All cases had solid fusion. Between the 2 groups, Scoliosis Research Society Outcomes Instrument-22 scores were similar at the final follow-up. No major acute complications occurred in both groups. CONCLUSIONS: VCD is a safe and effective method in treating rigid kyphotic deformity secondary to AS. VCD provides a larger correction angle in one segment and preserves more height of osteotomized vertebrae than PSO.

Lymphocyte-Related Inflammation and Immune-Based Scores Predict Prognosis of Chordoma Patients After Radical Resection.

The inflammatory microenvironment plays a critical role in the development and progression of malignancies. In the present study, we aimed to evaluate the prognostic value of lymphocyte-related inflammation and immune-based prognostic scores in patients with chordoma after radical resection, including the neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), monocyte-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII). A total of 172 consecutive patients with chordoma who underwent radical resection were reviewed. R software was used to randomly select 86 chordoma patients as a training set and 86 chordoma patients as a validation set. Potential prognostic factors were also identified, including age, sex, tumor localization, KPS, Enneking stage, tumor size, and tumor metastasis. Overall survival (OS) was calculated using the Kaplan-Meier method and multivariate Cox regression analyses. NLR, PLR, SII, Enneking stage, tumor differentiation and tumor metastasis were identified as significant factors from the univariate analysis in both the training and validation sets and were subjected to multivariate Cox proportional hazards analysis. The univariate analysis showed that NLR ≥1.65, PLR ≥121, and SII ≥370×109/L were significantly associated with poor OS. In the multivariate Cox proportional hazard analysis, SII, Enneking stage and tumor metastasis were significantly associated with OS. As noninvasive, low-cost, reproducible prognostic biomarkers, NLR, PLR and SII could help predict poor prognosis in patients with chordoma after radical resection. This finding may contribute to the development of more effective tailored therapy according to the characteristics of individual tumors.

Proper detailed parameters for S1 sacral alar iliac screw placement in the Chinese population, a 3D imaging study.

BACKGROUND: S1-AI technique may be used as a salvage technique in pelvic fixation of complex spinal deformity surgery. However, the proper detailed parameters in the Chinese population has not been analyzed before to instruct S1-AI screws placement and to ensure the safety of clinical application while the trajectory in pelvic changes significantly at each angle. RESULTS: The ideal S1AI screw trajectory could be obtained in 28 of 30 female patient images (93.3%) and in all of the male patient images (100%). The screws that have already been used clinically in S2AI pathways can be applied in S1AI fixations. CONCLUSION: It is feasible to place S1AI screws in 93.3% of female Chinese adult patients and in all male Chinese patients. Preoperative CT reconstruction should be performed to evaluate proper trajectory parameters and to avoid anterior violation.

Ankylosing spondylitis kyphosis surgical correction postoperative evaluation via SRS-22 domain investigation.

BACKGROUND: The SRS-22 is used to evaluate clinical outcomes in ankylosing spondylitis kyphosis patients. This study aimed to investigate the relationship between Scoliosis Research Society-22 (SRS-22) domains and satisfaction with management in patients who underwent surgical correction for ankylosing spondylitis kyphosis. The relationship between patient satisfaction and SRS-22 domain scores will feedback abundant information of therapeutic effect and significance for treatment guidance. METHODS: In this work, 106 patients with ankylosing spondylitis kyphosis at a single institution, who underwent posterior spinal fusion of five levels or more to the sacrum, completed SRS-22 evaluation preoperatively and followed up for a minimum of 2-year postoperation. Wilcoxon tests were performed to compare preoperative with 2-year postoperative scores. Spearman correlations were investigated to evaluate associations between the 2-year treatment satisfaction and therapeutic effect in SRS-22 domain scores. RESULTS: There were 12 females and 94 males with mean BMI of 16.4 kg/m2 and at the mean age of 46.3 years. All of the primary surgeries were treatments performed with mean follow-up of 26 months. A statistical improvement between paired pre- and 2-year postoperative SRS-22 domain scores and most radiographical parameters, commonly P ≤ 0.05, was designed and implemented. The majority of patients gave SRS-22 satisfaction score with 3.0 or more (88.5%) or 4.0 or more (68.8%), which are consistent with the moderate ceiling effect. Spearman coefficient correlations between the SRS-22 domain scores and patient satisfaction were all statistically significant, and they were from low to strong: [Mental (0.30), Activity (0.71), Pain (0.25), and Appearance (0.40)]. Furthermore, correlations for all radiographical and operative parameters were from low to strong. CONCLUSION: SRS-22 Activity domain correlates strongest with patient satisfaction in ankylosing spondylitis kyphosis patients who have undergone surgical correction at 2-year follow-up.