Hapln1 promotes dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping.

Hyaluronan and proteoglycan link protein 1 (Hapln1) supports active cardiomyogenesis in zebrafish hearts, but its regulation in mammal cardiomyocytes is unclear. This study aimed to explore the potential regulation of Hapln1 in the dedifferentiation and proliferation of cardiomyocytes and its therapeutic value in myocardial infarction with human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) and an adult mouse model of myocardial infarction. HiPSC-CMs and adult mice with myocardial infarction were used as in vitro and in vivo models, respectively. Previous single-cell RNA sequencing data were retrieved for bioinformatic exploration. The results showed that recombinant human Hapln1 (rhHapln1) promotes the proliferation of hiPSC-CMs in a dose-dependent manner. As a physical binding protein of Hapln1, versican interacted with Nodal growth differentiation factor (NODAL) and growth differentiation factor 11 (GDF11). GDF11, but not NODAL, was expressed by hiPSC-CMs. GDF11 expression was unaffected by rhHapln1 treatment. However, this molecule was required for rhHapln1-mediated activation of the transforming growth factor (TGF)-ß/Drosophila mothers against decapentaplegic protein (SMAD)2/3 signaling in hiPSC-CMs, which stimulates cell dedifferentiation and proliferation. Recombinant mouse Hapln1 (rmHapln1) could induce cardiac regeneration in the adult mouse model of myocardial infarction. In addition, rmHapln1 induced hiPSC-CM proliferation. In conclusion, Hapln1 can stimulate the dedifferentiation and proliferation of iPSC-derived cardiomyocytes by promoting versican-based GDF11 trapping and subsequent activation of the TGF-ß/SMAD2/3 signaling pathway. Hapln1 might be an effective hiPSC-CM dedifferentiation and proliferation agent and a potential reagent for repairing damaged hearts.

Bacillus pfraonensis sp. nov., a new strain isolated from a probiotic feed additive with low cytotoxicity and antimicrobial activity.

Probiotic products containing living microorganisms are gaining popularity, increasing the importance of their taxonomic status. A Bacillus-like isolate, 70 b, cultured from a probiotic feed additive, was ambiguity in taxonomic assignment and could be a novel member of Bacillus cereus group. The results of colony and cellular morphology, physiological and biochemical analysis mainly including growth performance, carbon source utilization, and rMLST and MLST were not conclusive. Fatty acids profile and molecular genetic analysis especially ANI, DDH, and core genome SNPs-based phylogenetic tree confirmed 70 b as one novel species of B. cereus group and proposed as Bacillus pfraonensis sp. nov. Comparative genomic analysis revealed the genetic differences between 70 b and other species of B. cereus group. Pseudomycoicidin was identified in 70 b. 70 b was active against multidrug-resistant pathogenic strains MRSA. The findings support 70 b is a novel species with low cytotoxicity and antimicrobial activity, and provides a better understanding of its unique characteristics and probiotic potential, and exploration of bioactive potential.

Does the Choice of Operative Side Affect the Clinical Outcome of Unilateral Percutaneous Kyphoplasty for Osteoporotic Vertebral Compression Fracture?

BACKGROUND: Studies have found that the rate of improvement in pain after percutaneous kyphoplasty (PKP) is 49% to 90%, and there are still some patients who may continue to sustain intractable back pain after surgery. OBJECTIVES: To compare the clinical efficacy and imaging results between unilateral PKP performed from the symptom-dominating side and the non-dominating side in OVCF treatment. STUDY DESIGN: Prospective study. SETTING: All data were from Honghui Hospital in Xi'an. METHODS: One hundred forty-two patients of osteoporotic vertebral compression fracture (OVCF) treated with unilateral PKP were eventually recruited and randomly assigned to either the A or B group. Patients in group A received PKP from the symptom-dominating side; patients in group B received PKP from the symptom non-dominating side. The demographic characteristics, related surgical information, and complications observed within both groups were recorded. The clinical outcomes evaluation included the visual analog scale (VAS) score for low back pain and the Oswestry Disability Index (ODI). Evaluation of imaging results included anterior height (AH), kyphosis angulation (KA), and contralateral distribution rate of bone cement. RESULTS: One hundred eighteen patients (48 men and 70 women; age range: 60-83 years), including 59 patients in the A group and 59 patients in the B group, were available for the complete assessment. There were 5 cases and 7 cases of bone cement leakage in groups A and B, respectively, which were asymptomatic para-vertebral or inter-vertebral leakage without intra-spinal leakage. Compared with the preoperative data, significant improvements in the VAS scores and ODI were observed at each follow-up interval. The VAS score and ODI in the A group were significantly lower than in the B group only within 2 months (P < 0.05). Compared with the preoperative data, the AH and KA in the 2 groups were improved (P < 0.05). There was no significant difference in AH and KA between the 2 groups at each follow-up interval (P > 0.05). LIMITATIONS: A single-center study. CONCLUSIONS: The unilateral PKP performed via the symptom-dominating side can effectively relieve back pain and improve the patient's quality of life at the early stage.

Anterior and Posterior Approaches for 4-Level Degenerative Cervical Myelopathy: Low-Profile Cage Versus Cervical Pedicle Screws Fixation.

(1) Background: The choice of surgical access for 4-level degenerative cervical myelopathy (DCM) remains controversial, and the clinical and radiological outcomes of anterior surgery using a low-profile cage (Low-P) versus posterior surgery using cervical pedicle screw fixation (CPS) have not been compared. (2) Methods: This is a retrospective controlled study conducted between January 2019 and June 2021 of 72 patients with 4-level DCM who underwent ACDF using a low-profile cage (n = 39) or laminectomy and instrument fusion using CPS (n = 33). The minimum follow-up time was 12 months. The outcomes were C2−7Cobb angle, C2−7sagittal vertical axis (SVA) fusion rate, the Japanese Orthopedic Association (JOA) score, pain visual analog scale (VAS), neck disability index (NDI), and complications. (3) Results: Both anterior and posterior procedures significantly improved the patients' quality-of-life parameters. Anterior cervical convexity and SVA significantly increased in both groups, but the SVA was greater in the posterior group than in the anterior group (p < 0.001). The C2−7 Cobb angle significantly improved in both groups postoperatively, and at the final follow-up, there was a slight but nonsignificant reduction in cervical lordosis in both groups (p = 0.567). There was a longer operative time, less intraoperative blood loss, and reduced mean hospital stay in the anterior group compared to the posterior group, with two cases of postoperative hematoma requiring a second operation, two cases of axial pain (AP), five cases of dysphagia, two cases of c5 palsy in the anterior group, and four cases of axial pain, and three cases of c5 palsy in the posterior group. According to Bridwell fusion grade, anterior fusion reached grade I in 28 cases (71.8%) and grade II in 10 cases (25.6%) in the anterior group, and posterior fusion reached grade I in 25 cases (75.8%) and grade II in 8 cases (24.2%) in the posterior group. (4) Conclusions: There was no difference between the anterior and posterior surgical approaches for MDCM in terms of improvement in neurological function. Posterior surgery using CPS achieved similar recovery of cervical anterior convexity as anterior surgery with a shorter operative time but was more invasive and had a greater increase in SVA. The use of Low-P in anterior surgery reduced the incidence of dysphagia and cage subsidence and was less invasive, but with a longer operative time.

Hydroxyapatite-Tethered Peptide Hydrogel Promotes Osteogenesis.

Hydroxyapatite (HAp) as natural bone composition is highly osteoinductive. To harvest its osteoinductivity in bone regenerative engineering, the HAp-supporting hydrogel is urgently needed to minimize inhomogeneous aggregation of HAp. Here, we developed a HAp-stabilizing hydrogel based on peptide self-assembly. FmocFFRR was efficient for HAp-capping due to arginine-phosphate interaction. Tethering FmocFFRR on the HAp surface facilitated self-assembly to form FmocFFRR/HAp hybrid hydrogel, enabling stable dispersion of HAp in it. The molecular interactions between FmocFFRR and HAp particles were studied using microscopic and spectral characterizations. FmocFFRR/HAp hydrogel exhibited more enhanced mechanical properties than FmocFFRR. The biocompatibility of FmocFFRR/HAp hydrogel was verified using an ATP assay and live-dead staining assay. More importantly, FmocFFRR/HAp hydrogel not only enabled cell attachment on its surface, but also supported 3D cell culturing inside the hydrogel. Further, 3D culturing of MC3T3-E1 preosteoblasts inside FmocFFRR/HAp hydrogel significantly enhanced the expressions of osteogenesis markers, including alkaline phosphate (ALP), type-I collagen (COL1), and osteocalcin (OCN), demonstrating the promoting effect of osteoblast differentiation. These findings inspire its potential application in bone regenerative engineering.

Biomechanical effects of different lateral mass injury patterns on subaxial cervical fracture dislocations after anterior cervical surgery: a finite element study.

OBJECTIVE: The lateral mass joint plays an important role in maintaining the mechanical stability of the subaxial cervical spine. We first performed a three-dimensional finite element (FE) biomechanical study to evaluate the local mechanical stability of subaxial cervical fracture dislocations after anterior-only fixation for lateral mass injuries of varying severity. METHODS: A three-dimensional FE model of the subaxial cervical spine with simple anterior fixation for C5-6 fracture dislocation was reconstructed. According to their different morphological characteristics of unilateral lateral mass injuries, the lateral mass injury was divided into six types. The range of motion (ROM) of each part and the stress of the cage, each intervertebral disc, titanium plate, and screw stress were recorded. RESULTS: The ROM of C3-4, C4-5, C5-6, and C6-7 in type 4 was higher than that of the other five types. The maximum equivalent stress on C4-5 intervertebral discs, titanium plates, and screws in type 4 under various sports loads was higher than that produced by the other load types. In the stress cloud diagram of the front titanium plate and screws, the degree of stress was the highest in type 4. Stress placed on each part of the model, from high to low, was as follows: plate, screw, C6, C5, and C7. CONCLUSION: Greater injury severity is associated with higher stress on the plate and screw with exercise loads. Type 4 lateral mass injuries, characterized by ipsilateral pedicle and lamina junction fractures, significantly affected biomechanical stability after simple anterior fixation.

Diagnostic Value of Multimodal Intraoperative Neuromonitoring by Combining Somatosensory-With Motor-Evoked Potential in Posterior Decompression Surgery for Thoracic Spinal Stenosis.

Background: Intraoperative neuromonitoring (IONM) has become an increasingly essential technique in spinal surgery. However, data on the diagnostic value of IONM in predicting impending postoperative neurological deficits (PONDs) for patients who underwent posterior decompression surgery for thoracic spinal stenosis (TSS) are limited. Furthermore, patients who are at the highest risk of waveform changes during the surgery remain unknown. Our purpose was to (1) assess the diagnostic accuracy of IONM by combining somatosensory-evoked potential (SSEP) with motor-evoked potential (MEP) in predicting PONDs for patients who underwent the surgery and (2) identify the independent risk factors correlated with IONM changes in our study population. Methods: A total of 326 consecutive patients who underwent the surgery were identified and analyzed. We collected the following data: (1) demographic and clinical data; (2) IONM data; and (3) outcome data such as details of PONDs, and recovery status (complete, partial, or no recovery) at the 12-month follow-up visit. Results: In total, 27 patients developed PONDs. However, 15, 6, and 6 patients achieved complete recovery, partial recovery, and no recovery, respectively, at the 12-month follow-up. SSEP or MEP change monitoring yielded better diagnostic efficacy in predicting PONDs as indicated by the increased sensitivity (96.30%) and area under the receiver operating characteristic (ROC) curve (AUC) value (0.91). Only one neurological deficit occurred without waveform changes. On multiple logistic regression analysis, the independent risk factors associated with waveform changes were as follows: preoperative moderate or severe neurological deficits (p = 0.002), operating in the upper- or middle-thoracic spinal level (p = 0.003), estimated blood loss (EBL) ≥ 400 ml (p < 0.001), duration of symptoms ≥ 3 months (p < 0.001), and impairment of gait (p = 0.001). Conclusion: Somatosensory-evoked potential or MEP change is a highly sensitive and moderately specific indicator for predicting PONDs in posterior decompression surgery for TSS. The independent risks for IONM change were as follows: operated in upper- or middle-thoracic spinal level, presented with gait impairment, had massive blood loss, moderate or severe neurological deficits preoperatively, and had a longer duration of symptoms. Clinical Trial Registration: [http://www.chictr.org.cn]; identifier [ChiCTR 200003 2155].

The feasibility and safety of cocktail treatment of triple anti-inflammatory agents loaded with gelatin sponge promotes early recovery after posterior percutaneous endoscopic cervical discectomy.

PURPOSE: To investigate whether a cocktail therapy of dexamethasone, ropivacaine, dexmedetomidine, and vitamin B12 can achieve satisfactory pain relief and promote early functional recovery after PPECD. METHODS: Eighty single-level patients with CDH who received PPECD were retrospectively divided into two groups: the cocktail and control groups. Clinical data were recorded and evaluated by a dedicated physician who was not involved in the patient's treatment. The primary clinical outcomes included visual analog scores (VASs) for upper limber pain and neck disability index (NDI) scores. The follow-up time points were preoperatively and postoperative 1 week, 1 month, 3 months, 6 months, and 12 months. The modified MacNab criteria was used to evaluate the surgical effect of the last follow-up. RESULTS: The follow-up data of 74 cases were complete, except 6 cases lost to follow-up. There was no significant difference between the two groups in demographics, duration of symptoms, operation stage (p > 0.05), and operation time (80.5 ± 5.5 vs. 81.5 ± 3.5 min). The VAS in the upper limbs pain was significantly higher postoperatively than preoperatively in both groups (p < 0.05). The cocktail group had a lower VAS than the control group 1 week postoperatively (p < 0.05); however, VAS not different between groups at the remaining time points. The NDI scores were significantly better postoperatively than preoperatively, and no significant differences were seen when comparing nodes at postoperative follow-up (p > 0.05). In the control group, two cases with foraminal stenosis were found to have unrelieved pain in the early postoperative period, but the pain was relieved at the final follow-up and did not convert to open decompression surgery. CONCLUSIONS: Cocktail treatment, in which a drug sustained-release material made of gelatin sponge was impregnated with dexamethasone, ropivacaine, dexmedetomidine and vitamin B12, facilitates pain relief and early postoperative recovery after PPECD.

Blockage of ERCC6 Alleviates Spinal Cord Injury Through Weakening Apoptosis, Inflammation, Senescence, and Oxidative Stress.

Objective: Spinal cord injury (SCI) is a devastating disease resulting in lifelong disability, but the molecular mechanism remains unclear. Our study was designed to observe the role of excision repair cross-complementing group 6 (ERCC6) following SCI and to determine the underlying mechanism. Methods: SCI mouse models and LPS-induced microglia cell models were established. ERCC6 expression was blocked by ERCC6-siRNA-carrying lentivirus. Nissl staining was utilized for detecting neuronal damage, and apoptosis was analyzed with TUNEL and Western blotting (apoptotic markers). Immunofluorescence was used for measuring macrophage markers (CD68 and F4/80) and astrocyte and microglia markers (GFAP and Iba-1). Pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) were measured via ELISA. Senescent cells were estimated via SA-ß-Gal staining as well as Western blot (senescent markers p21 and p27). Oxidative stress was investigated by detecting the expression of 4-HNE, Nrf2, and Keap1, and intracellular ROS levels. Results: ERCC6 expression was remarkably upregulated both in the spinal cord of SCI mice and LPS-induced microglia cells. ERCC6 deficiency alleviated neuronal damage and apoptosis. Macrophage infiltration and inflammatory response were suppressed by si-ERCC6 treatment. Moreover, ERCC6 blockage ameliorated astrocyte and microglia activation and cell senescence in the damaged spinal cord. Excessive oxidative stress was significantly decreased by ERCC6 knockdown in SCI. Conclusion: Collectively, ERCC6 exerts crucial functions in mediating physiological processes (apoptosis, inflammation, senescence, and oxidative stress), implying that ERCC6 might act as a prospective therapeutic target against SCI.

Can paraspinal muscle degeneration be a reason for refractures after percutaneous kyphoplasty? A magnetic resonance imaging observation.

BACKGROUND: Vertebral augmentation (VA) techniques are used to treat acute osteoporotic vertebral compression fractures (OVCFs). However, the incidence of recurrent vertebral fractures after VA is controversial. Various factors have been discussed in the literature, but no convincing study on the quality of paraspinal muscles has been reported. The purposes of this study were to evaluate the changes in paraspinal muscles and discuss the relationship between paraspinal muscle degeneration and vertebral refractures after percutaneous kyphoplasty (PKP). METHODS: This retrospective study was conducted in patients who underwent PKP for an initial OVCF between July 2017 and August 2018. Patients were followed up and categorized in the refractured or non-refractured group. A final magnetic resonance imaging (MRI) scan and a preoperative MRI scan were used to determine the measurements. The paraspinal muscles at the mid-height level of the initial fractured vertebral body were measured using regions of interest (ROIs), including the cross-sectional area (CSA) and signal intensity (SI). The changes in the observed data were compared between the groups using rank-sum tests. RESULTS: Overall, 92 patients were enrolled in the study; 33 of them sustained vertebral refractures during the follow-up and the other 59 patients did not. There were no significant differences in terms of sex, age, preoperative bone mineral density, and body mass index between the groups (all, P > 0.05). The refractured group had a significantly higher decrease in the ROI-CSA and CSA/SI, and a higher increase in ROI-SI, compared with the preoperative data (all, P < 0.05). CONCLUSIONS: The quality of paraspinal muscles significantly decreased in patients with new OVCFs after PKP. This brings a new perspective to the study of postoperative recurrent fractures; patients and physicians need to pay more attention to the efficacy of bed rest and bracing.

Full-Endoscopic Decompression with the Application of an Endoscopic-Matched Ultrasonic Osteotome for Removal of Ossification of the Thoracic Ligamentum Flavum.

BACKGROUND: Resection of the ossification of the thoracic ligamentum flavum (OTLF) with a high-speed burr may cause a high rate of perioperative complications, such as dural laceration and/or iatrogenic spinal cord injury. OBJECTIVES: The aim of this study was to investigate the safety and feasibility of the endoscopic-matched ultrasonic osteotome in full-endoscopic spinal surgery for direct removal of OTLF. STUDY DESIGN: Retrospective study. SETTING: All data were from Honghui Hospital in Xi'an. METHODS: This study conducted between December 2017 and December 2018, included 27 consecutive patients who met the study criteria, had single-level OTLF, and underwent full-endoscopic decompression under local anesthesia. The postoperative follow-up was scheduled at 1, 3, 6, and 12 months postoperatively. Outcomes evaluations included the Visual Analog Scale (VAS) score for lower extremity pain and the modified Japanese Orthopaedic Association (mJOA) score and improvement rate for the assessment of thoracic myelopathy. Removal of OTLF was measured by comparing the pre- and postoperative computed tomography (CT) and magnetic resonance imaging (MRI) scans. RESULTS: The operation was completed in all patients without conversion to open surgery. The operation time ranged from 65 to 125 minutes (average, 83.7 ± 12.3 minutes). All patients were followed up for 12 to 18 months, with an average follow-up of 14.3 ± 1.3 months. Satisfactory neurologic decompression was confirmed by postoperative CT and MRI, and no revision surgery was required. The VAS and mJOA scores showed statistically higher improvement at the 1-month follow-up and the last follow-up compared with the preoperative assessment (P < 0.05). According to the improvement rate at the final follow-up, 20 cases were classified as good, 6 cases were fair, and 1 case remained unchanged. LIMITATIONS: A single-center, noncontrol study. CONCLUSIONS: The endoscopic-matched ultrasonic osteotome can be considered quite safe and feasible for direct removal of OTLF during full-endoscopic spinal surgery in strictly selected patients, as this allows for effective direct decompression of OTLF while minimizing trauma and instability. In addition, because of the design characteristics of the ultrasonic osteotome, surgical complications, especially dural tears and spinal cord injury, can also be effectively controlled.

Can Additional Facet Joint Block Improve the Clinical Outcome of Kyphoplasty for Acute Osteoporotic Vertebral Compression Fractures?

BACKGROUND: Percutaneous kyphoplasty (PKP) has been reported to provide a favorable analgesic effect for pain caused by osteoporotic vertebral compression fractures (OVCFs). However, a systematic review demonstrated that pain relief was only reported for approximately 86% of kyphoplasty treatments. OBJECTIVES: To explore whether an additional facet joint block (FJB) can minimize pain and improve the clinical outcome of PKP in patients with acute OVCFs. STUDY DESIGN: Prospective study. SETTING: All data were from Honghui Hospital in Xi'an. METHODS: According to the inclusion and exclusion criteria, 194 patients were eventually included in our study; they were randomly divided into 2 groups of 97 patients each and treated with either PKP + FJB or PKP alone. Follow-up consultations were scheduled 1 day, 3 days, 1 week, 1 month, 3 months, and 1 year postoperatively; the demographic characteristics, related surgical information, and complications observed within both groups were recorded. The clinical evaluation parameters included the intraoperative satisfaction score, the Visual Analog Scale (VAS) score, and the Oswestry Disability Index (ODI). RESULTS: A total of 171 patients (61 men and 110 women; age range: 62-85 years) completed the full postoperative follow-up schedule, with 83 patients in the PKP + FJB group and 88 in the PKP group. No significant differences were observed in the genders, ages, preoperative bone mineral density, surgical levels, or volume of cement injected between the 2 groups (P > 0.05, respectively). The average duration of the surgeries in the PKP + FJB group was slightly longer than that in the PKP group (35.5 ± 4.8 min vs. 31.8 ± 4.3 min; P = 0.038), and in terms of the clinical outcomes, the average intraoperative satisfaction score was significantly higher in the PKP + FJB group (8.6 ± 1.1 vs. 6.3 ± 1.3; P < 0.001). Compared with the preoperative data, significant improvements in the VAS scores of back pain and ODI were observed at each follow-up interval (P < 0.05, respectively). These scores were significantly higher in the PKP + FJB group than in the PKP group; however, this was only observed within the first month after the procedure. LIMITATIONS: A single-center noncontrol study. CONCLUSIONS: The addition of an FJB (which in our study involved a unique combination of ropivacaine, prednisolone, and vitamin B12) improved the short-term clinical outcome of PKP for acute OVCFs. The local anti-inflammatory and analgesic effects on the facet joints resulted in higher intraoperative satisfaction and lower VAS and ODI scores for the first postoperative month when compared with the PKP group.

Posterior Ligament-Bone Injury Classification and Severity Score: A Novel Approach to Predict the Failure of Anterior-only Surgery for Subaxial Cervical Facet Dislocations.

STUDY DESIGN: Clinical case series. OBJECTIVE: The aim of this study was to propose a novel posterior ligament-bone injury classification and severity (PLICS) score system that can be used to reflect the severity of subaxial cervical fracture dislocations (SCFDs) and predict the failure of anterior-only surgery; and to measure the intraobserver and interobserver reliability of this system. SUMMARY OF BACKGROUND DATA: The approach selection for SCFDs is controversial. Although the anterior approach is familiar for most surgeons, postoperative hardware failure and/or delayed cervical deformity is a nonnegligible complication. METHODS: Ten patients were randomly selected for intraobserver reliability evaluation on two separate occasions, one month apart. Another 30 patients were randomly selected, and the interobserver reliability was measured by comparing results of each case between each reviewer and averaging. To analyze the difference in the PLICS score, 354 patients fulfilled the follow-up were divided into stable and unstable groups according to whether radiologically stable was observed during follow-up. RESULTS: For the intraobserver reliability, the mean intraclass correlation coefficient for the 10 reviewers was 0.931. For the interobserver reliability, the mean interobserver correlation coefficient for the three elements was 0.863. Among 16 patients with PLICS score ≥7, two patients in the stable group manifested with severe injury of the posterior ligamentous complex (PLC); extremely unstable lateral mass fractures with or without severe injury of PLC were detected in the 14 patients of the unstable group. CONCLUSION: The proposed PLICS score system showed excellent intraobserver and interobserver reliability. When a PLICS score is >7 or 7 accompanied by extremely unstable lateral mass fractures, the risk of postoperative failure after an anterior-only reconstruction is high and supplemental posterior strengthening can be considered.Level of Evidence: 4.

When is the circumferential stabilization necessary for subaxial cervical fracture dislocations? The posterior ligament-bone injury classification and severity score: a novel treatment algorithm.

OBJECTIVE: To propose a novel classification and scoring system called the posterior ligament-bone injury classification and severity score (PLICS) that offers a quantitative score to guide the need for posterior stabilization in addition to anterior reconstruction for subaxial cervical fracture dislocations (SCFDs). METHODS: A total of 456 patients with SCFDs were prospectively included. Patients with PLICS ≥ 7 together with extremely unstable lateral mass fracture (EULMF) were classified as high-risk group, and the other patients were classified as low-risk group. For patients in the low-risk group, anterior-only reconstruction was performed; for patients in the high-risk group, additional posterior lateral mass fixation and fusion was performed after anterior reconstruction. Clinical outcome evaluation included using the visual analogue score (VAS), the Neck Disability Index (NDI), and the American Spinal Injury Association (ASIA) impairment scale. The change in the local sagittal alignment kyphosis Cobb angle was also recorded. RESULTS: A total of 370 patients (81.1%) completed the minimal 12-month follow-ups, including 321 patients of low-risk group and 49 patients of high-risk group. Compared with the average VAS score preoperatively, the score at 12-month follow-up was significantly improved (from 6.1 + 0.3 to 1.1 + 0.2 in the low-risk group, P < 0.001; from 6.4 + 0.2 to 1.4 + 0.2 in the high-risk group, P < 0.001). The average NDI score at the 12-month follow-up was statistically low in the low-risk group (8.8 + 2.5 vs 13.8 + 3.4, P = 0.034). At least more than one grade improvement in the ASIA scale was observed in 80.5% of all patients. The local kyphosis Cobb angle at the injured segment averaged improved in both groups. CONCLUSION: A PLICS score ≥ 7 together with EULMF can be the threshold for posterior stabilization in addition to anterior reconstruction for the patients with SCFDs.

The Regulatory Role of Rho GTPases and their Substrates in Osteoclastogenesis.

Pathological bone loss diseases (osteolysis, Paget's diseases) are commonly caused by the excessive differentiation and activity of osteoclasts. The Rho GTPases family members Rac1/2 (Rac1 and Rac2) have been reported for their special role in exerting multiple cellular functions during osteoclastic differentiation, which includes the most prominent function on dynamic actin cytoskeleton rearranging. Besides that, the increasing studies demonstrated that the regulating effects of Rac1/2 on the osteoclastic cytoskeletal organization are through the GEFs member Dock5. Although the amount of relevant studies on this topic is still limited, several excellent studies have been reported that extensively explored the molecular mechanisms involved in Rac1/2 and Dock5 during the osteoclastogenesis regulation, as well as their role as the therapeutic target in bone loss diseases. Herein, in this review, we aim to focus on recent advances studies for extensively understanding the role of Rho GTPases Rac1/2 and Dock5 in osteoclastogenesis, as well as their role as a potential therapeutic target in regulating osteoclastogenesis.

[Polymethylmethacrylate-augmented screw fixation in treatment of senile thoracolumbar tuberculosis combined with severe osteoporosis].

OBJECTIVE: To explore the safety and effectiveness of polymethylmethacrylate-augmented screw fixation (PASF) in the treatment of elderly thoracolumbar tuberculosis combined with severe osteoporosis. METHODS: The clinical data of 20 elderly patients with thoracolumbar tuberculosis and severe osteoporosis who underwent PASF after anterior or posterior debridement and bone grafting and met the selection criteria between December 2012 and December 2014 were retrospectively analyzed. There were 8 males and 12 females with an average age of 68.5 years (range, 65-72 years). T value of bone mineral density was -4.2 to -3.6, with an average of -3.9. There were 12 cases of thoracic tuberculosis, 3 cases of thoracolumbar tuberculosis, and 5 cases of lumbar tuberculosis. The diseased segments involved T 3-L 4, including 11 cases of single-segment disease, 6 cases of double-segment disease, and 3 cases of multi-segment disease. The disease duration was 3-9 months, with an average of 6 months. The preoperative spinal nerve function of the patients was evaluated by the American Spinal Injury Association (ASIA) grading. There were 2 cases of grade A, 5 cases of grade B, 6 cases of grade C, 4 cases of grade D, and 3 cases of grade E. Postoperative imaging examination was used to evaluate the bone graft fusion and paravertebral abscess absorption, and to measure the Cobb angle of the segment to evaluate the improvement of kyphosis. The levels of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were tested. The visual analogue scale (VAS) score, Oswestry disability index (ODI), and ASIA grading were used to evaluate the effectivreness before operation, at 1 month after operation, and at last follow-up. The clinical cure of tuberculosis was also evaluated. RESULTS: All operation successfully completed. The operation time was 154-250 minutes, with an average of 202 minutes; the intraoperative blood loss was 368-656 mL, with an average of 512 mL. All 20 patients were followed up 18-42 months, with an average of 26.8 months. The postoperative pain and symptoms of tuberculosis in all patients relieved, and the paravertebral abscess was absorbed, reaching the cure standard for spinal tuberculosis. All bone grafts fusion achieved within 1 year after operation. Only 1 case had asymptomatic bone cement leakage into the paravertebral veins, and the remaining patients had no serious complications such as bone cement leakage in the spinal canal, pulmonary embolism, and neurovascular injury. At last follow-up, spinal cord nerve function significantly improved when compared with preoperative one. Among them, ASIA grading were 7 cases of grade C, 8 cases of grade D, and 5 cases of grade E, showing significant difference when compared with preoperative one ( Z=2.139, P=0.000). VAS score, ODI score, segmental Cobb angle, ESR, and CRP at 1 month after operation and at last follow-up were significantly improved when compared with preoperative ones ( P<0.05); there was no significant difference between 1 month after operation and last follow-up ( P>0.05). During the follow-up, no complications such as failure of internal fixation, proximal junctional kyphosis, or tuberculosis recurrence occurred. CONCLUSION: For elderly patients with thoracolumbar tuberculosis and severe osteoporosis, PASF treatment is safe and effective.

Spinal Epidural Hematoma After Percutaneous Kyphoplasty: Case Report and Literature Review.

OBJECTIVE: To present the case of a patient on long-term anticoagulants who developed acute spinal epidural hematoma (SEH) after percutaneous kyphoplasty (PKP) without signs of major cement extravasation to the spinal canal. METHODS: A 64-year-old woman with long-term oral antiplatelet drugs underwent the L1 PKP. Immediately after the operation, the back pain improved significantly without neurological deficit. However, 12 hours later, she developed progressive weakness of the bilateral lower limbs. No intraspinal cement leakage was obvious on the postoperative lumbar radiograph and computed tomography. RESULTS: An emergency MRI examination revealed a high signal aggregation in front of the spinal cord from T12 to L1, indicating spinal cord compression. The SEH was verified and removed during the laminectomy from T12-L1. Following the decompression surgery, the neurological deficit of the lower limbs improved. On follow-up after 6 months, the muscle strength of the bilateral lower limbs had returned to normal. CONCLUSION: For the patient with long-term oral antiplatelet drugs or coagulation malfunction, the transpedicle approach or that via the costovertebral joint with a smaller abduction angle is recommended to reduce the risk of injury to the inner wall of the pedicle. For progressive aggravation of neurological dysfunction after surgery, SEH formation should be suspected despite the absence of intraspinal bone cement leakage. Secondary emergency decompression should be considered to avoid permanent damage to spinal cord nerve function caused by continuous compression.

Mesenchymal stem cells regulate inflammatory milieu within degenerative nucleus pulposus cells via p38 MAPK pathway.

It has been established that excessive apoptosis of nucleus pulposus cells (NPCs) are responsible for pathogenesis of human intervertebral disc degeneration (IDD). The present study aimed to shed light on the molecular mechanisms underlying the protective effects of mesenchymal stem cells (MSCs) on NPCs in an inflammatory environment. NPCs were treated with TNF-α to induce inflammation and then co-cultured with Wharton's Jelly-derived MSCs (WJ-MSCs)without direct interaction. The levels of inflammation markers (IL-1ß, IL-6 and IL-8) in NPCs were detected by performing enzyme-linked immunosorbent assay (ELISA), and expression of metalloproteases and aggrecan, as well as the activity of p38 MAPK pathway were determined through immunoblotting. SB-203580 was used to inhibit p38 signaling, prior to evaluation of the effects of Wharton's Jelly-derived MSCs (WJ-MSCs) on inflammatory response within the co-cultured NPCs. After TNF-α treatment, the levels of inflammatory cytokines, MMP-3, and MMP-13 in NPCs were increased whereas aggrecan was decreased, which was then dramatically reversed by WJ-MSCs co-culture. Likewise, WJ-MSCs suppressed TNF-α-induced phosphorylation of p38 MAPK signaling components including p38, ASK-1, MKK-3 and MKK-6. Blocking p38 MAPK pathway enhanced the anti-inflammatory impact of WJ-MSCs, and there was no significant difference between NPCs co-cultured with WJ-MSCs or the cells cultured alone. WJ-MSCs co-culture mitigate TNF-α-induced inflammatory response and ECM degeneration in NPCs, the major pathological events are implicated in IDD development, probably by suppressing the p38 MAPK signaling cascade.

Comparison of Clinical and Radiologic Outcome Between Mini-Open Wiltse Approach and Fluoroscopic-Guided Percutaneous Pedicle Screw Placement: A Randomized Controlled Trial.

OBJECTIVE: To compare clinical efficacy, radiographic outcome, and radiation exposure between mini-open pedicle screw (MPS) fixation with the Wiltse approach and percutaneous pedicle screw (PPS) fixation in treatment of young and middle-aged patients with thoracolumbar burst fractures. METHODS: Of 60 patients with thoracolumbar vertebrae fractures treated in our hospital from January 2017 to January 2018, 30 were randomly assigned to the MPS group and 30 were randomly assigned to the PPS group. Clinical efficacy, radiographic outcome, and radiation exposure were compared between the 2 groups. RESULTS: The average age of patients was 42.2 ± 6.7 years in the MPS group and 43.0 ± 6.9 years in the PPS group (P = 0.668). There was no significant difference between the 2 groups in blood loss, hospital stay, postoperative visual analog scale score for back pain, and Oswestry Disability Index score. The vertebral body height and vertebral body angle of the MPS group were significantly better than those of the PPS group at the last follow-up. There was no significant difference in the accuracy rate of pedicle screw placement between the MPS group and the PPS group; the facet joint violation was significantly higher in the PPS group. The average radiation exposure dosage was lower in the MPS group. CONCLUSIONS: Both MPS fixation with the Wiltse approach and PPS fixation are safe and effective in the treatment of single-segment thoracolumbar vertebral fractures. Nevertheless, considering the surgical duration, radiation exposure, facet joint violation, vertebral body height, and vertebral body angle at the last follow-up, MPS fixation with the Wiltse approach is a better choice than PPS.