[Neuroprotective effect and mechanism of cPLA2 inhibitor increases autophagic flux on spinal cord injury].

OBJECTIVE: To investigate the mechanism of cytosolic phospholipase A2(cPLA2) inhibitor to improve neurological function after spinal cord injury (SCI). METHODS: Thirty-six 3 months old female SD rats, with body mass (280±20) g, were divided into three groups (n=12):sham group, SCI group, and SCI+ arachidonyl trifluoromethyl ketone(AACOCF3) group. Balloon compression SCI model was established in all three groups. In the sham model group, the spinal cord compression model was created after the balloon was placed without pressure treatment, and the remaining two groups were pressurized with the balloon for 48 h. After successful modeling, rats in the SCI+AACOCF3 group were injected intraperitoneally with AACOCF3, a specific inhibitor of cPLA2. The remaining two groups of rats were injected intraperitoneally with saline. The animals were sacrificed in batches on 7 and 14 days after modeling, respectively. And the damaged spinal cord tissues were sampled for pathomorphological observation, to detect the expression of cPLA2 and various autophagic fluxPrelated molecules and test the recovery of motor function. RESULTS: Spinal cord histomorphometry examination showed that the spinal cord tissue in the sham group was structurally intact, with normal numbers and morphology of neurons and glial cells. In the SCI group, spinal cord tissue fractures with large and prominent spinal cord cavities were seen. In the SCI+AACOCF3 group, the spinal cord tissue was more intact than in the SCI group, with more fused spinal cord cavities, more surviving neurons, and less glial cell hyperplasia. Western blot showed that the sham group had the lowest protein expression of LC3-Ⅱ, Beclin 1, p62, and cPLA2 compared with the SCI and SCI+AACOCF3 groups (P<0.05) and the highest protein expression of LC3-Ⅰ (P<0.05). P62 and cPLA2 expression in the SCI group were higher than in the SCI+AACOCF3 group (P<0.05). Behavioral observations showed that the time corresponding to BBB exercise scores was significantly lower in both the SCI and SCI+AACOCF3 groups than in the sham group (P<0.05). Scores at 3, 7, and 14 days after pressurization were higher in the SCI+AACOCF3 group than in the SCI group (P<0.05). CONCLUSION: cPLA2 inhibitors can reduce neuronal damage secondary to SCI, promote neurological recovery and improve motor function by improving lysosomal membrane permeability and regulating autophagic flux.

[Research progress of causes and strategies in revision surgery for atlantoaxial dislocation].

Atlantoaxial dislocation (AAD) is a kind of life-threatening atlantoaxial structural instability and a series of neurological dysfunction caused by common multidisciplinary diseases. The operation risk is extremely high because it is adjacent to the medulla oblongata and the location is deep. With the increase of the number of operations in the upper cervical region, postoperative complications such as failure of internal fixation, non fusion of bone graft and poor prognosis gradually increase.Incomplete primary operation, non fusion of bone graft, infection and congenital malformation are the potential causes. In addition, considering the objective factors such as previous graft, scar formation and anatomical marks changes, revision surgery is further difficult. However, there is currently no standard or single effective revision surgery method. Simple anterior surgery is an ideal choice in theory, but it has high risk and high empirical requirements for the operator;simple posterior surgery has some defects, such as insufficient reduction and decompression;anterior decompression combined with posterior fixation fusion is a more reasonable surgical procedure, but many problems such as posterior structural integrity and multilevel fusion need to be considered.This article reviews the causes and strategies of AAD revision surgery.

Occipitocervical Revision Surgery Using the Bicortical Screw and Plate System for Failed Craniovertebral Junction Stabilization.

BACKGROUND: To evaluate the clinical efficacy and safety of the modified technique utilizing the occipital bicortical screws and plate system in occipitocervical revision surgery. METHODS: Between October 2010 and May 2018, 12 consecutive patients were retrospectively evaluated. All patients had posterior occipitocervical resurgery utilizing modified technique of bicortical screws and occipital plate. The measurements of extracranial occiput on midline were conducted on computed tomography (CT) scans. The thickness of the occipital bone at the location of external occipital protuberance and below 15 mm were evaluated, respectively. For the procedure, the trajectory was drilled perpendicular to the external occipital protuberance for the specified depth with a depth-limited drilling, 2 mm away from the internal bone plate, then the trajectory was deepened at intervals of 1 mm each time until reaching the internal bone plate. Meanwhile, a probe was used to explore all the walls of the trajectory. Bicortical screws were inserted to the occipital plate and the depth of penetration was less than 2 mm from the internal bone plate. Clinical efficacy and radiographic evaluation were followed up. RESULTS: The thickest point was the external occipital protuberance, which was 15.49 ± 1.47 mm and decreased gradually on the midline to 13.41 ± 1.60 mm at below 15 mm. Twelve cases (mean age 41.17 years; range, 24-62 years), including five males and seven females, were followed up for 24.08 months (14-32 months). The interval time was 40.42 months (3-156 months) after the initial operation. At the final follow-up, JOA score increased from 8.58 ± 2.53 before surgery to 12.67 ± 1.84 (P < 0.05) and VAS score improved from 6.17 ± 1.21 to 2.08 ± 1.32 (P < 0.05). Besides, clinical symptoms were relieved in all patients after revision surgery. All patients had rigid internal fixations with bone fusion and no major complications occurred. CONCLUSIONS: Posterior occipitocervical plate-screw system with bicortical screws had the advantages of safety, simple and promising efficacy without excessive tissue release or intraspinal manipulation, proving that it's valuable as a modified technique for occipitocervical revision surgery.

Flexion Dysfunction of Atlanto-Occipital Joint Associated with Cervical Spondylosis.

OBJECTIVE: To investigate the association between atlanto-occipital radiographic alignment in flexion and cervical spondylosis (CS). METHODS: This is a retrospective case-control study. CS patients were recruited from our hospital, and the age/gender/body mass index (BMI)-matched healthy controls were selected from the subjects in health examinations at the same hospital between January 2015 and May 2019. A total of 464 subjects was included in the study. There are 282 males and 182 females. The ages of patients were 20 to 67 years, and the mean age was 33.9 years. CS patients were considered the case group. Based on surgical treatments, they were subdivided into non-operation group and operation group. The operation group and non-operation group had 45 and 187 patients, respectively, while 232 subjects were included in the control group. The angle between McGregor's line and C1 line (O-C1 angle) was evaluated on images taken in flexion (F-OC) and neutral positions (N-OC) independently. The relationship between the FOC (FOC=F-OC-N-OC) and Neck Disability Index (NDI) was examined, and the involvement of the FOC in the onset of CS was analyzed. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off for detecting an increased risk of CS. RESULTS: The median follow-up time was 51.6 months (25-115 months). The case groups, especially the operation group, tended to be older (55.8 ± 11.2 vs 41.6 ± 13.8 vs 23.5 ± 5.5 years, P < 0.001), have a higher NDI score (12.2 ± 4.5 vs 6.2 ± 2.1 vs 3.2 ± 1.2, P < 0.001), and longer medical history (10.5 ± 9.5 vs 6.8 ± 11.2 years, P < 0.001). One-way analysis of variance showed statistically significant differences in FOC between the control and case groups (1.4° ± 1.2° vs 3.6° ± 1.9° vs 7.2° ± 2.0°, P < 0.001). Besides, a post-hoc Tukey test showed a lower FOC in the operation group compared with that in the non-operation group (1.4° ± 1.2° vs 3.6° ± 1.9°, P < 0.001). Using FOC as a radiological predictive model to predict CS, the cut-off value was 4.2°. Using FOC as a radiological predictive model to predict CS, the area under the curve (AUC) was 0.86 (95% CI: 0.78-0.92, P < 0.001). In the univariable risk analysis model, conditional logistic regression showed that the FOC level was an independent factor with an important role in the risk of CS. The odds rose to 8.2 times when FOC reached the level under 4.2° (OR = 8.2; 95% CI: 6.4-10.0; P < 0.001). There existed a significant negative correlation between FOC levels and NDI (r = -0.451, P = 0.016). CONCLUSIONS: Stiff O-C1 , which is defined as FOC ≤ 4.2°, represented decreased flexion dysfunction of atlanto-occipital joint and is closely associated with high risk for the occurrence of CS. This finding could show a possible relationship between upper and lower cervical spine and help spine surgeons to understand the pathological process of CS and implement appropriate management.

Personality Traits Affect the Cost-Effectiveness of Total Knee Arthroplasty.

OBJECTIVE: To assess the clinical benefit and compare the cost-effectiveness of total knee arthroplasty (TKA) in patients with different personality traits. METHODS: The present study was retrospectively conducted from January 2017 to May 2018. A total of 232 patients between 46 and 71 years old who underwent unilateral, primary TKA with the diagnosis of knee osteoarthritis were interviewed. Three types of data were required to compare the cost-effectiveness differences among groups: personality traits, postoperative clinical outcomes about health-related quality of life, and costs associated with TKA. Personality was assessed using the Eysenck Personality Questionnaire, functional outcome was assessed through the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) questionnaire, and costs were evaluated. Besides, the marginal cost-effectiveness ratio (MCER) as the primary outcome, which relates the direct costs to the associated patient benefit as assessed by the clinical endpoint ($/quality-adjusted life years [QALY]), was compared among different personality traits. All information for this study was acquired by directly interviewing the patients and reviewing the medical computer records at our hospital. RESULTS: Two hundred and eleven patients completed the final analysis with an average of 24.6 months follow-up postoperatively. The choleric group, sanguine group, melancholic group, and phlegmatic group has 41, 70, 46, and 54 patients, respectively. A statistically significant difference in MECR, QALYs, and postoperative WOMAC existed among different personality traits (all P < 0.05). There was no significant difference in mean age (P = 0.588), body mass index (BMI) (P = 0.790), smoking (P = 0.934), heavy drinking (P = 0.994), chronic comorbidities (all P > 0.05), preoperative albumin <3.5 g/dL (P = 0.991), and American Society of Anaesthesiologists (ASA) score (P = 0.687) among personality traits. More women tend to be melancholic in comparison to other personality traits (P = 0.016). Melancholic patients attested inferiority of TKA compared with other personality traits, who would pay for the same QALYs at the highest costs (P < 0.05). By contrast, sanguine patients have a more cost-effective TKA than other personality traits, as they pay the least money for the same QALYs (P < 0.05). Although phlegmatic and choleric patients seemingly have moderate gains from TKA, in general, the extroversion (measured by the extroversion subscale) and stability (measured by the neuroticism subscale) displayed more pleasurable QALYs in comparison with introversion and instability (P < 0.05). Sensitivity analysis showed that the results mentioned above appeared not to be sensitive when varying key parameters (prosthesis survival and life expectancy) in a one-way sensitivity analysis. Sanguine and melancholic patients still have the lowest and highest MCER in comparison with choleric and phlegmatic traits (P < 0.05). The multivariate logistic regression showed that RA (adjusted OR = 1.3, 95% CI = 1.2-1.4, P < 0.01), ASA Class I-II (adjusted OR = 0.9, 95% CI = 0.8-1.0, P < 0.001), sanguine (adjusted OR = 0.8, 95% CI = 0.7-0.9, P < 0.001) and melancholic (adjusted OR = 1.2, 95% CI = 1.1-1.3, P < 0.001) were significantly associated with MCER. CONCLUSIONS: Before surgery, screening the melancholic patients would significantly reduce the economic burden, avoid unnecessary suffering, and shorten the recovery period.

Phosphoglycerate kinase 1 silencing by a novel microRNA microRNA-4523 protects human osteoblasts from dexamethasone through activation of Nrf2 signaling cascade.

Nuclear-factor-E2-related factor 2 (Nrf2) cascade activation can ameliorate dexamethasone (DEX)-induced oxidative injury and death in human osteoblasts. Phosphoglycerate kinase 1 (PGK1) depletion is shown to efficiently activate Nrf2 signaling by inducing methylglyoxal modification of Kelch-like ECH-associated protein 1 (Keap1). We here identified a novel PGK1-targeting microRNA: microRNA-4523 (miR-4523). RNA fluorescent in situ hybridization, RNA pull-down, and Argonaute-2 RNA immunoprecipitation results confirmed a direct binding between miR-4523 and PGK1 mRNA in primary human osteoblasts and hFOB1.19 osteoblastic cells. Forced overexpression of miR-4523, using a lentiviral construct, robustly decreased PGK1 3'-UTR (untranslated region) luciferase activity and downregulated its expression in human osteoblasts and hFOB1.19 cells. Furthermore, miR-4523 overexpression activated the Nrf2 signaling cascade, causing Keap1-Nrf2 disassociation, Nrf2 protein stabilization, and its nuclear translocation as well as transcription activation of Nrf2-dependent genes (NQO1, GCLC, and HO1) in human osteoblasts. By expressing a UTR-null PGK1 construct, miR-4523 overexpression-induced Nrf2 cascade activation was however largely inhibited. Importantly, DEX-induced reactive oxygen species production, oxidative injury, and cell apoptosis were significantly attenuated by miR-4523 overexpression in human osteoblasts and hFOB1.19 cells. Such actions by miR-4523 were abolished by Nrf2 shRNA or knockout, but mimicked by PGK1 knockout (using CRISPR/Cas9 method). In PGK1 knockout human osteoblasts, miR-4523 overexpression failed to further increase Nrf2 cascade activation and offer osteoblast cytoprotection against DEX. Significantly, miR-4523 is downregulated in human necrotic femoral head tissues of DEX-taking patients. Together, PGK1 silencing by miR-4523 protected human osteoblasts from DEX through activation of the Nrf2 signaling cascade.

[Function of NOD-like receptor protein 1 inflammasome in traumatic central nervous system injury].

NOD-like receptor protein 1 (NLRP1) inflammasome plays an important role in the innate immune response of human body. It can promote the activation of cysteinyl aspartate specific proteinases(Caspases), further activate interleukin-18 and interleukin-1 ß, and mediate pyroptosis. NlRP1 inflammasome plays a role in traumatic central nervous system injury. In this study, the structure of NLRP1 inflammasome, the activation of NLRP1 inflammasome in traumatic central nervous system injury and the treatment with NLRP1 inflammasome as a target are reviewed.

Raloxifene Prevents Early Periprosthetic Bone Loss for Postmenopausal Women after Uncemented Total Hip Arthroplasty: A Randomized Placebo-Controlled Clinical Trial.

OBJECTIVE: To examine the results of raloxifene for prevention of periprosthetic bone loss around the femoral stem in patients undergoing total hip arthroplasty (THA). METHODS: Between January 2015 and May 2017, 240 female patients between 55 and 80 years underwent primary THA and were randomly allocated to receive 60 mg raloxifene hydrochloride per day (treatment group, TG, n = 120) or placebo (control group, CG, n = 120) orally at bedtime using computer-generated randomization sequence generation. Baseline data, the Western Ontario McMaster Universities Osteoarthritis Index (WOMAC), women's quality of life (QoL) score, bone mineral density (BMD) around the prosthesis, and adverse events were compared between the two groups. The measuring range of BMD around the prosthesis was divided into seven regions of interest (ROI). The sample size was calculated to detect a mean difference in BMD of 0.15 g/cm2 with a standard deviation (SD) of 0.3. The error was set at 0.05 and the power level at 90% with additional compensation for a possible dropout rate of 20%. RESULTS: A total of 240 participants in the study up to 24 months after THA. There were no significant differences in the mean BMD of all the zones between groups before surgery (all P > 0.05). However, there were significant differences in the BMD of Gruen zones 4 and 7 between groups at 6 months postoperatively (both P < 0.05); there were significant differences in Gruen zones 1, 4, 6, and 7 at 12 months postoperatively (all P < 0.01); there were significant differences in Gruen zones 1, 2, 4, 6, and 7 at 24 months postoperatively (all P < 0.001). Patients taking raloxifene reported higher QoL scores, with better improvement in BMD in all areas except in zones 3 and 5 compared with the control group. There were no significant differences in WOMAC pain (P = 0.4045), WOMAC function (P = 0.4456) and women's QoL scores (P = 0.5983) between groups before surgery. However, WOMAC pain, WOMAC function and women's QoL score in the treatment group were significantly better at all time points (all P < 0.05). Patients in the treatment group showed no increased adverse events, including cardiac events, stroke, venous thromboembolism, and gynecological cancer (all P > 0.05), but did show decreased odds of breast cancer in comparison with those using a placebo (P = 0.0437). CONCLUSION: Raloxifene can help inhibit bone loss around the prosthesis and improve the QoL of postmenopausal women after THA with no increased adverse events, and can even decrease the odds of breast cancer.

[Clinical practice guideline of integrated traditional Chinese and western medicine：atlantoaxial dislocation (AAD) (2019)].

EDITOR'S NOTE: EDITOR'S NOTE In 2019, the clinical practice guideline of integrated traditional Chinese and western medicine atlantoaxial dislocation (ADD) was developed by the professional committee of spine medicine of the Chinese Association for Integration of Chinese and Western medicine, aiming at the major clinical problems of atlantoaxial dislocation (AAD) endangering the life center of the medulla oblongata in the field of spine surgery. More than 40 experts at home and abroad in the field of cervical spine surgery organized the first guide for the diagnosis and treatment of AAD. Guided by the principles of evidence based medicine and the consensus of experts, this guideline is based on the theory of "combination of disease and syndrome, from supervision to treatment" for the diagnosis and treatment of AAD；based on the treatment principles of "spinal cord decompression, reconstruction of atlantoaxial stability"；based on Tan technology, Goel technology, Abumi technology and other core technologies for surgical treatment. The main content includes four parts：AAD diagnosis standard, TCM syndrome differentiation, clinical classification, treatment strategy and method. It provides academic guidance to solve the clinical situation of AAD, which is "unclear definition of diagnosis and classification, confused choice of treatment strategy". ABSTRACT: Clinical Practice Guideline of Integrated Traditional Chinese and Western Medicine：Atlantoaxial Dislocation (AAD) was enacted by the academic committee of spine surgery of integrated traditional Chinese and Western medicine. The guideline's recommendations forms by evidence-based medicine and the expert consensus of Integrative Medicine. The guidement principles is "spinal cord decompression, reconstruction of atlantoaxial stability". The objective of the guideline is providing an academic suggestion. The main contents include diagnostic criteria, traditional Chinese medicine's (TCM) dialectical method, clinical classification, treatment strategies and methods.

Topical Injection of Tranexamic Acid via a Drain Plus Drain-Clamping to Reduce Blood Loss in Degenerative Lumbar Scoliosis Surgery.

OBJECTIVE: The aim of the present study was to investigate whether an innovative way of administering tranexamic acid (TXA), that is, injecting it retrogradely through the drain and clamping it for 1 h, can reduce postoperative bleeding after degenerative lumbar scoliosis surgery. METHODS: Sixty degenerative lumbar scoliosis patients who underwent posterior lumbar decompression with fusion of three or more levels were retrospectively enrolled and categorized into three groups (TXA, Gelfoam, and control groups). The demographic distribution, operative parameters, length and amount of Hemovac drainage, blood transfusion rate, length of stay, laboratory results (complete blood count and coagulogram), and the postoperative complications were collected and analyzed. RESULTS: The age of patients in the Gelfoam group was significantly younger than in the TXA and control groups (59.75 ± 6.95 vs 66.10 ± 8.80, P = 0.016 and 59.75 ± 6.95 vs 67.90 ± 5.33, P = 0.000, respectively). There were no significant differences in sex, body mass index, comorbid medical status, and operation level between each of the two groups. The three groups did not differ significantly in estimated blood loss during surgery, the mean red blood cell transfusion requirement during hospitalization, and the entire perioperative allogenic blood transfusion rate. The postoperative total blood loss and total drainage were lower in the TXA group than in the control group (1027.14 ± 466.56 vs 1390.07 ± 314.85 mL, P = 0.006; 322.20 ± 187.32 vs 605.50 ± 184.70 mL, P = 0.000, respectively). The length of drainage retention in the TXA group was significantly shorter than in the Gelfoam and control groups (46.10 ± 9.00 vs 68.00 ± 12.31 h, P = 0.000 and 46.10 ± 9.00 vs 76.40 ± 10.97 h, P = 0.000, respectively). The TXA and Gelfoam groups also had significantly shorter hospital stays than the control group (7.50 ± 0.95 vs 9.80 ± 2.44 days, P = 0.000, and 7.90 ± 1.16 vs 9.80 ± 2.44 days, P = 0.003, respectively). At discharge, the mean hemoglobin and hematocrit level were significantly higher in the TXA group compared with the control group (11.77 ± 1.78 g/dL vs 10.67 ± 0.94 g/dL, P = 0.002; 34.82 ± 3.57% vs 31.79 ± 3.85%, P = 0.014). No significant difference was identified with respect to prothrombin time, activated partial thromboplastin time, and D-dimmer among groups (P > 0.05). The three groups were comparable in wound problem incidences. Symptomatic deep vein thrombosis and pulmonary embolism were not observed in this study. CONCLUSION: Topical injection of TXA retrogradely via a drain at the end of a degenerative lumbar scoliosis operation and clamping the drain for an hour can effectively decrease the postoperative blood loss and the length of hospitalization without increasing the complication rate.

A modified posterior wedge osteotomy with interbody fusion for the treatment of thoracolumbar kyphosis with Andersson lesions in ankylosing spondylitis: a 5-year follow-up study.

BACKGROUND: Andersson lesions (ALs), also known as spondylodiscities, destructive vertebral lesions and spinal pseudarthrosis, usually occur in patients with ankylosing spondylitis (AS). Inflammatory and traumatic causes have been proposed to define this lesion. Different surgical approaches including anterior, posterior, and combined anterior and posterior procedure have been used to address the complications, consisting of mechanical pain, kyphotic deformity, and neurologic deficits. However, the preferred surgical procedure remains controversial. The aim of this study was to illustrate the safety, efficacy, and feasibility of a modified posterior wedge osteotomy for the ALs with kyphotic deformity in AS. METHODS: From June 2008 to January 2013, 23 patients (18 males, 5 females) at an average age of 44.8 years (range 25-69 years) were surgically treated for thoracolumbar kyphosis with ALs in AS via a modified posterior wedge osteotomy in our department. All sagittal balance parameters were assessed by standing lateral radiography of the whole spine before surgery and during the follow-up period. Assessment of radiologic fusion at follow-up was based on the Bridwell interbody fusion grading system. Ankylosing spondylitis quality of life (ASQoL) and visual analog scale (VAS) scores were performed to evaluate improvements in daily life function and back pain pre-operatively and post-operatively. Paired t tests were used to compare clinical data change in parametric values before and after surgery and the Mann-Whitney U test was employed for non-parametric comparisons. The radiographic data change was evaluated by repeated measure analysis of variance. RESULTS: The mean operative duration was 205.4 min (range 115-375 min), with an average blood loss of 488.5 mL (range 215-880 mL). Radiographical and clinical outcomes were assessed after a mean of 61.4 months of follow-up. The VAS back pain and ASQoL scores improved significantly in all patients (7.52 ±â€Š1.31 vs. 1.70 ±â€Š0.70, t = 18.30, P < 0.001; 13.87 ±â€Š1.89 vs. 7.22 ±â€Š1.24, t = 18.53, P < 0.001, respectively). The thoracolumbar kyphosis (TLK) changed from 40.03 ±â€Š17.61° pre-operatively to 13.86 ±â€Š6.65° post-operatively, and 28.45 ±â€Š6.63° at final follow-up (F = 57.54, P < 0.001), the thoracic kyphosis (TK) changed from 52.30 ±â€Š17.62° pre-operatively to 27.76 ±â€Š6.50° post-operatively, and 28.45 ±â€Š6.63° at final follow-up (F = 57.29, P < 0.001), and lumbar lordosis (LL) changed from -29.56 ±â€Š9.73° pre-operatively to -20.58 ±â€Š9.71° post-operatively, and -20.73 ±â€Š10.27° at final follow-up (F = 42.50, P < 0.001). Mean sagittal vertical axis (SVA) was improved from 11.82 ±â€Š4.55 cm pre-operatively to 5.12 ±â€Š2.42 cm post-operatively, and 5.03 ±â€Š2.29 cm at final follow-up (F = 79.36, P < 0.001). No obvious loss of correction occurred, according to the lack of significant differences in the sagittal balance parameters between post-operatively and the final follow-up in all patients (TK: 27.76 ±â€Š6.50° vs. 28.45 ±â€Š6.63°, TLK: 13.86 ±â€Š6.65° vs. 14.42 ±â€Š6.7°, LL: -20.58 ±â€Š9.71° vs. -20.73 ±â€Š10.27°, and SVA: 5.12 ±â€Š2.42 cm vs. 5.03 ±â€Š2.29 cm, all P > 0.05, respectively). CONCLUSIONS: The modified posterior wedge osteotomy is an accepted surgical procedure for treating thoracolumbar kyphosis with ALs in AS and results in satisfactory local kyphosis correction, solid fusion, and good clinical outcomes.

PGK1 depletion activates Nrf2 signaling to protect human osteoblasts from dexamethasone.

Activation of nuclear-factor-E2-related factor 2 (Nrf2) cascade can alleviate dexamethasone (DEX)-induced oxidative injury and death of human osteoblasts. A recent study has shown that phosphoglycerate kinase 1 (PGK1) inhibition/depletion will lead to Kelch-like ECH-associated protein 1 (Keap1) methylglyoxal modification, thereby activating Nrf2 signaling cascade. Here, in OB-6 osteoblastic cells and primary human osteoblasts, PGK1 silencing, by targeted shRNA, induced Nrf2 signaling cascade activation, causing Nrf2 protein stabilization and nuclear translocation, as well as increased expression of ARE-dependent genes (HO1, NQO1, and GCLC). Functional studies demonstrated that PGK1 shRNA largely attenuated DEX-induced oxidative injury and following death of OB-6 cells and primary osteoblasts. Furthermore, PGK1 knockout, by the CRISPR/Cas9 method, similarly induced Nrf2 signaling activation and protected osteoblasts from DEX. Importantly, PGK1 depletion-induced osteoblast cytoprotection against DEX was almost abolished by Nrf2 shRNA. In addition, Keap1 shRNA mimicked and nullified PGK1 shRNA-induced anti-DEX osteoblast cytoprotection. At last we show that PGK1 expression is downregulated in human necrotic femoral head tissues of DEX-taking patients, correlating with HO1 depletion. Collectively, these results show that PGK1 depletion protects human osteoblasts from DEX via activation of Keap1-Nrf2 signaling cascade.

[Manual reduction combined with percutaneous vertebroplasty for the treatment of osteoporotic vertebral compression fractures with intravertebral clefts].

OBJECTIVE: To explore the therapeutic efficacy of manual reduction combined with percutaneous vertebroplasty in treating osteoporotic vertebral compression fractures(OVCFs) with intravertebral clefts. METHODS: The clinical data of 94 patients with osteoporotic vertebral compression fractures with intravertebral clefts treated from January 2014 to January 2017 were retrospectively analyzed. The patients were divided into group A and group B according to different operative methods. In group A, 45 patients were treated with unilateral approach PVP, including 17 males and 28 females, aged (75.35±11.82) years old, with a bone density T-value of (-4.28±0.65) g/cm³; in group B, 49 patients treated with manual reduction combined with unilateral approach PVP, including 19 males and 30 females, aged (76.79±9.64) years old, with a bone density T-value of (-4.33±0.72) g/cm³. The operation time, bone cement injection volume and postoperative complications of two groups were recorded. The VAS and ODI scores of two groups were analyzed respectively at 1, 12, 18 months after operation. Vertebral height and kyphosis Cobb angle of two groups were compared immediately after surgery and 12, 18 months after operation. The distribution of bone cement in the vertebral body was observed and its distribution excellent rate was calculated. RESULTS: There was no significant difference in operation time between two groups. The amount of bone cement injection was(8.42±1.24) ml in group A and(9.19±1.09) ml in group B, and the difference between two groups was statistically significant(P<0.05). No spinal nerve root injury during operation and no complications including pulmonary embolism, bone cement toxicity and infection were found in two groups. There were 5 cases of bone cement leakage in group A and 4 cases in group B, which did not cause corresponding clinical symptoms and were not treated additionally. The distribution of bone cement in group A was excellent in 25 cases, good in 19 cases, poor in 1 case and in group B was excellent in 45 cases, good in 4 cases. The distribution excellent rate of bone cement was higher in group B than in group A (P<0.05). The VAS and ODI scores before operation and 1, 12, 18 months after operation were 8.29±0.74, 2.59±0.14, 3.75±0.38, 3.84±0.88 and 40.04±3.16, 9.24±2.82, 12.27±2.64, 15.83±2.58 in group A, 8.22±0.82, 2.54±0.19, 2.81±0.23, 2.82±0.45 and 39.98±2.05, 9.16±2.10, 9.46±2.41, 9.76±2.46 in group B. There was no significant difference in VAS and ODI scores at 1 month after operation between two groups (P>0.05), but group A was higher than group B at 12 and 18 months after operation (P<0.05). The vertebral height and Cobb angle before surgery, immediately after surgery, and 12, 18 months after surgery in group A were(59.17±1.42)%, (85.95±2.19)%, (75.27±3.45)%, (68.34±2.24)% and(23.83±3.37)°, (15.26±2.61)°, (17.63±2.16)°, (19.46±2.54)°, and in group B were(59.31±1.87)%, (89.19±2.53)%, (88.62±2.51)%, (88.59±2.62)% and(24.72±3.78)°, (14.91±2.28)°, (15.48±2.55)°, (15.86±2.81)°. Vertebral height Immediately after surgery was greater in group B than in group A and Cobb angle in group B was smaller than in group A (P<0.05). During follow-up, there was no significant change in vertebral height in group B, while vertebral body recollapse in group A(P<0.05). CONCLUSIONS: In the treatment of osteoporotic vertebral compression fractures with intravertebral clefts, the manual reduction combined with PVP is more effective than single PVP, which can effectively prevent vertebral body recollapse and improve the long-term efficacy of patients.

[Safety depth of acupuncture at Yamen (GV 15) in patients with atlantoaxial dislocation].

OBJECTIVE: To explore and compare the safety depths of perpendicular and oblique acupuncture at Yamen (GV 15) in patients with atlantoaxial dislocation (AAD) and healthy volunteers. METHODS: One bundred and seventy-seven patients with atlantoaxial dislocation were selected as an AAD group, and 207 patients without atlantoaxial dislocation and with normal anatomical structure were selected as a normal group. All participants were moderately sized. The MRI scanning of the cervical vertebra was performed, and the safety depth of perpendicular and oblique acupuncture at Yamen (GV 15) was calculated on the sagittal image. RESULTS: In the AAD group, the safety depth of men was (45.33±5.17) mm for perpendicular acupuncture and (48.58±4.41) mm for oblique acupuncture; the safety depth of women was (44.17±7.80) mm for perpendicular acupuncture and (47.49±7.32) mm for oblique acupuncture. In the normal group, the safety depth of men was (47.72±5.06) mm for perpendicular acupuncture and (42.69±5.53) mm for oblique acupuncture; the safety depth of women was (44.63±5.85) mm for perpendicular acupuncture and (39.88±6.18) mm for oblique acupuncture. The safety depth of men and women for oblique acupuncture was longer than that for perpendicular acupuncture in the AAD group (P<0.01); the safety depth of men and women for oblique acupuncture was shorter than that for perpendicular acupuncture in the normal group (P<0.01). The safety depth of perpendicular and oblique acupuncture between men and women was not significant in the AAD group (P>0.05); the safety depth of perpendicular and oblique acupuncture for men was longer than that for women in the normal group (P<0.01). For men, the safety depth of perpendicular acupuncture in the AAD group was shorter than that in the normal group (P<0.01), while the safety depth of oblique acupuncture in the AAD group was longer than that in the normal group (P<0.01). For women, the safety depth of perpendicular acupuncture in the AAD group was similar with that in the normal group (P>0.05), while the safety depth of oblique acupuncture in the AAD group was longer than that in the normal group (P<0.01). CONCLUSION: The safe depth of acupuncture at Yamen (GV 15) has significantly changed under AAD, so during the clinical acupuncture the needle insertion should be less than its safe depth.

[Clinical study on spinal cord decompression combined with traditional Chinese medicine for the treatment of cervical spondylotic myelopathy].

OBJECTIVE: To compare the clinical effect between spinal card decompression combined with traditional Chinese medicine and simple spinal card decompression for cervical spondylotic myelopathy. METHODS: From June 2012 to June 2015, 73 patients with cervical spondylotic myelopathy were treated, including 42 males and 31 females, aged from 29 to 73 years old with a mean of 50.9 years old. The patients were divided into the simple operation group (34 cases) and the operation combined with traditional Chinese medicine group(39 cases) according to the idea of themselves. The anterior discectomy or subtotal corpectomy with internal fixation or posterior simple open-door decompression with lateral mass screw fixation were performed in the patients. Among them, 39 cases were treated with traditional Chinese medicine after surgery. The Japanese orthopedic association (JOA) score of spinal cord function, the improvement rate of neural function, the neck dysfunction index (NDI) score and the governor vessel stasis syndrome score were compared between two groups preoperative and postoperative 1 week, 1 month and the final follow-up respectively. The internal fixation and the condition of spinal cord decompression were observed by CT, MRI and X-rays before and after operation. RESULTS: All the operations were successful, no injuries such as dura mater, spinal cord and nerve root were found. All the wounds were healed without infection except one patient had a superficial infection. It was solved after intermittent debridement and anti-infective therapy. Hematoma occurred in 1 case, complicated with spinal cord compression, caused incomplete paralysis, and promptly performed the re-operation to remove the hematoma without any obvious sequelae. All the patients were followed up from 12 to 24 months, (14.6±0.8) months for simple operation group and (13.5±0.7) months for operation combined with traditional Chinese medicine group, and there was no significant difference(P>0.05). The scores of JOA, NDI and the governor's vessel stasis syndrome in simple operation group were 8.31±3.15, 29.91±4.52, 6.58±1.31 before operation, and 10.21±2.58, 18.67±4.31, 8.24±1.18 one week after operation, and 11.38±2.85, 16.11±3.18, 8.91±2.11 one month after operation, and 12.21±3.12, 14.61±3.28, 9.12±1.56 at final follow-up, respectively; and in operation combined with traditional Chinese medicine group were 8.29±3.47, 30.83±4.14, 6.38±1.81before operation, and 10.48±2.39, 17.59±5.14, 8.33±1.57 one week after operation, and 12.14±3.12, 13.14±3.21, 9.55±2.49 one month after operation, and 13.85±3.34, 12.11±2.51, 10.33±1.95 at final follow-up, respectively. Postoperative JOA , NDI, and the governor vessel stasis syndrome score of two groups were significantly higher than preoperativee(P<0.05). There was no significant difference in JOA, NDI, and the governor vessel stasis syndrome score between two groups one week after operation (P>0.05). The above items in operation combined with traditional Chinese medicine group was better than that of simple operation group one month and final follow-up after operation (P<0.05). The improvement rate of neural function in simple operation group was (67.59±10.78)%, and in operation combined traditional Chinese medicine group was (66.88±12.15)%, there was no significant difference between two groups(P>0.05). There were no complications such as internal fixation failure or re-dislocation of atlas by postoperative CT, MRI and X-rays examination. CONCLUSIONS: Spinal card decompression for the treatment of cervical spondylotic myelopathy can extend the spinal canal, relieve the compression of nerve, achieve the deoppilation of governor vessel, the regulation of qi and blood, the restore of Yangqi, combined with traditional Chinese medicine of activating blood removing stasis, warming yang and activating meridians, reinforcing liver benefiting kidney, which may obtain better clinical effect.

[Analysis of clinical efficacy of unilateral open-door cervical laminoplasty combined with foraminotomy for cervical ossification of posterior longitudinal ligament].

OBJECTIVE: To explore the clinical efficacy of unilateral open-door laminoplasty combined with foraminotomy for cervical ossification of posterior longitudinal ligament(OPLL). METHODS: The clinical data of 45 patients with OPLL underwent surgical treatment between September 2011 and September 2015 were retrospectively analyzed. There were 26 males and 19 females with a mean age of 53.6 years old(ranged from 28 to 71 years). Among them, 24 cases received the surgery of unilateral open-door cervical laminoplasty combined with foraminotomy(combined group), and 21 cases received a single unilateral open-door cervical laminoplasty(single group). Operation time, intraoperative blood loss, complications including C5 nerve root palsy and axial symptoms were compared between two groups. Pre-and post-operative Japanese Orthopedic Association(JOA) score, improvement rate of neurological function, Neck Disability Index(NDI) score, and cervical Cobb angle were recorded and analyzed between the two groups. RESULTS: All the patients were followed up for 12-24 months, with an average of (14.3±2.8) months for combined groups and (13.7±3.1) months for single group, and no significant difference was found between the two groups(P>0.05). There was no significant difference in operation time and intraoperative blood loss between two groups(P>0.05). Postoperative JOA scores obtained obvious improvement in all patients(P<0.05). However, there was no significant difference between two groups for the improvement rate of neurological function(P>0.05). At final follow-up, NDI scores of combined group and single group were 13.6±1.8 and 16.1±2.4 respectively, there was significant difference between two groups(P<0.05). The incidence of C5 nerve root palsy was lower in combined group(4.2%) than that of single group (28.6%). There was no significant difference in incidence rate of axial symptoms between two groups(P>0.05). There was no significant difference in cervical Cobb angle between pre-and post-operative conditions, or between two groups(P>0.05). CONCLUSIONS: Unilateral open-door cervical laminoplasty combined with foraminotomy is an effective method to treat cervical OPLL, which could provide sufficient decompression of spinal cord and nerve root, prevent the C5 nerve root palsy.

[Effect of Buyanghuanwu decoction on the expression of platelet activating factor after acute spinal cord injury in rats].

OBJECTIVE: To investigate the effect and mechanism of Buyanghuanwu decoction on platelet activating factor expression in spinal cord tissue of model of acute upper cervical spinal cord injury in rats. METHODS: Sixty SPF grade 3-month-old female Wistar rats were randomly divided into sham operation group, model group, methylprednisolone group and Buyanghuanwu decoction (Traditional Chinese Medicine group, TCM), with 15 rats in each group. The first day after the modeling, the methylprednisolone group were treated by injection of the tail vein for a total of 24 h, the first dose of 30 mg/kg, followed by a dose of 5.4 mg/kg·h, and 1 time per 4 h. The traditional Chinese medicine group was prepared with a medium dose of Buyanghuanwu decoction granules which were prepared into a solution containing 2 g/ml of granules, 3.5 g/kg per day gavage, was equivalent to 1 time the amount of adult consumption. The model group and the sham operation group were given equal volume of normal saline for 2 times a day for 2 weeks. The recovery of nerve function was evaluated by BBB classification at 1, 3, 7, 14 days after treatment. The expression of PAF in the segment of spinal cord injury was detected by double antibody sandwich (ELISA) method at 1, 7, and 14 d postoperatively. RESULTS: At the first day after treatment, BBB score in model, TCM and methylprednisolone groups were lower than that of sham operation group(P<0.01), but there was no difference among the three groups(P>0.05). At 7, 14 days afer treatment, BBB score in TCM and methylprednisolone groups were higher than that of model group significantly(P<0.01); but there were no significant difference between TCM group and methylprednisolone group(P>0.05). PAF expression in TCM group and methylprednisolone group were lower than that of model group at 7, 14 day afer treatment significantly (P<0.05); but there were no significant difference between TCM group and methylprednisolone group (P>0.05). CONCLUSIONS: Buyanghuanwu decoction treatment after acute upper cervical spinal cord injury can significantly improve locomotor recovery by inhibiting the expression of PAF.

[Effects of decompression combined with electro-acupuncture on rat with acute severe upper cervical spinal cord compression injury].

OBJECTIVE: To explore the effect and underlying mechanism of decompression(DE)combined with Governor Vessel(GV)electro-acupuncture(EA) on rats with acute severe upper cervical spinal cord compression injury. METHODS: Thirty SPF rats were randomly divided into 5 groups(control group A, B and experiment group C, D, E), 6 rats in each group. The model of acute severe upper cervical spinal cord compression injury were made by forcing a balloon catheter put in atlas pillow clearance. The group A was blank one, the group B put balloon catheter in atlas pillow clearance without forcing, and the group C, D, E sustained compressed for 48 h. The group C received electric acupuncture intervention, selecting the Baihui and Dazhui point, having the continuous wave and frequency of 2 Hz, with the treatment time of 15 min and continuous treatment for 14 d; the group D received methylprednisolone intervention, injected by caudal vein; the group E did not received any intervention again. The arterial blood and injured spinal cord tissue of all the rats were obtained after 14 days' treatment, and BBB score was used to evaluate the change of each group hind limbs motor function, the contents of platelet activating factor(PAF) in injured spinal cord tissue and blood serum were assess by ELISA method; the Caspase-9 expression for each group after 14 days' treatment was assess by Western blot method. RESULTS: BBB scores were(21.000±0.000) points at the 6 time points, that was, 1 h, 48 h after forcing in control group, 24 h, 3 d, 7 d, 14 d after treating in experiment group; the score of experimental groups (group C, D, E) were always lower than control groups(group A, B); compared with group E, group C and D were significantly higher(P<0.05); and there was no significant difference between group C and group D(P>0.05). The results of PAF by ELISA method to measure:the concentration of serum PAF, there was no statistical difference among group A, B, D, E (P>0.05), group C was lower than the other groups (P<0.05); the concentration of tissue PAF, there was no significant difference between group A and group B(P>0.05), group D was significantly higher than that of group A, B, and C(P<0.05), group E was the highest one than that of the other groups(P<0.05). Western blot med tests showed that the Caspase-9 protein expression in group A and B was similar (P>0.05), group C was higher than that of group A and B(P<0.05), group D was higher than group A, B and C(P<0.05), group E was the highest than that of group A, B, C and D (P<0.05). CONCLUSIONS: Decompression and Governor Vessel electro-acupuncture on acute severe upper cervical spinal cord compression injury had a better effect compare with decompression and methylprednisolone or simple decompression only, its mechanism may be related to lower the PAF levels and downregulating Caspase-9 protein expression in spinal injury tissue.

Effects of decompression joint Governor Vessel electro-acupuncture on rats with acute upper cervical spinal cord injury.

Decompression is the major therapeutic strategy for acute spinal cord injury, but there is some debate about the time window for decompression following spinal cord injury. An important goal and challenge in the treatment of spinal cord injury is inhibiting or reversing secondary injury. Governor Vessel electroacupuncture can improve symptoms of spinal cord injury by inhibiting cell apoptosis and improving the microenvironment of the injured spinal cord. In this study, Governor Vessel electroacupuncture combined with decompression at different time points was used to treat acute spinal cord injury. The rat models were established by inserting a balloon catheter into the atlanto-occipital space. The upper cervical spinal cord was compressed for 12 or 48 hours prior to decompression. Electroacupuncture was conducted at the acupoints Dazhui (GV14) and Baihui (GV 20) (2 Hz, 15 minutes) once a day for 14 consecutive days. Compared with decompression alone, hind limb motor function recovery was superior after decompression for 12 and 48 hours combined with electroacupuncture. However, the recovery of motor function was not significantly different at 14 days after treatment in rats receiving decompression for 12 hours. Platelet-activating factor levels and caspase-9 protein expression were significantly reduced in rats receiving electroacupuncture compared with decompression alone. These findings indicate that compared with decompression alone, Governor Vessel electroacupuncture combined with delayed decompression (48 hours) is more effective in the treatment of upper cervical spinal cord injury. Governor Vessel electroacupuncture combined with early decompression (12 hours) can accelerate the recovery of nerve movement in rats with upper cervical spinal cord injury. Nevertheless, further studies are necessary to confirm whether it is possible to obtain additional benefit compared with early decompression alone.