Changes in Blood Pressure is Associated with Bone Loss in US Adults: A Cross-Sectional Study from NHANES 2005-2018.

Hypertension and osteoporosis are common geriatric diseases, sharing similar risk factors. This study aims to investigate this association and explore relatively mixed variables. Our study included 12,787 eligible participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Included participants had valid data on hypertension and osteoporosis, without tumors, liver diseases, gout or thyroid diseases. We explored the association between hypertension and osteoporosis by logistic regression and examined blood pressure and BMD/BMC by linear and non-linear regression. Moreover, we used machine learning models to predict the importance of various factors in the occurrence of osteoporosis and evaluated causality by mendelian randomization. Our study found that osteoporosis is significantly associated with hypertension [OR 2.072 (95% CI 2.067-2.077), p < 0.001]. After adjusting for co-variances, the association remained significant [OR 1.223 (95% CI 1.220-1.227), p < 0.001]. Our study showed that osteoporosis is positively associated with hypertension in the US population. A variety of factors influence this relationship. Specific regulatory mechanisms and confounding factors need to be further investigated.

Elucidating the role of RBM5 in osteoclastogenesis: a novel potential therapeutic target for osteoporosis.

Osteoporosis is a prevalent bone disease with multigene involved, and the molecular mechanisms of its pathogenesis are not entirely understood. This study aims to identify novel key genes involved in osteoporosis to discover potential pharmacological targets. We analyzed three microarray datasets and identified four differentially expressed genes. The LASSO model indicated that RNA-binding motif protein 5 (RBM5) is associated with osteoporosis and is a potential drug target. We conducted the Spearman correlation analysis and found 52 genes that were significantly related to RBM5. Enrichment analysis showed that these genes were primarily involved in RNA splicing and osteoclast differentiation pathways. By using lentivirus-based shRNA, we successfully knocked down RBM5 expression in RAW264.7 cell line, which showed that RBM5 knockdown significantly impaired their differentiation potential to mature osteoclasts and significantly inhibited bone-resorbing activity. RT-qPCR analyses revealed the expression of osteoclastogenesis marker genes was downregulated along with RBM5 expression. These findings suggest that RBM5 plays a crucial role in the pathogenesis of osteoporosis and provides a new potential pharmacological target.

Supramolecular Hydrogel Microspheres of Platelet-Derived Growth Factor Mimetic Peptide Promote Recovery from Spinal Cord Injury.

Neural stem cells (NSCs) are considered to be prospective replacements for neuronal cell loss as a result of spinal cord injury (SCI). However, the survival and neuronal differentiation of NSCs are strongly affected by the unfavorable microenvironment induced by SCI, which critically impairs their therapeutic ability to treat SCI. Herein, a strategy to fabricate PDGF-MP hydrogel (PDGF-MPH) microspheres (PDGF-MPHM) instead of bulk hydrogels is proposed to dramatically enhance the efficiency of platelet-derived growth factor mimetic peptide (PDGF-MP) in activating its receptor. PDGF-MPHM were fabricated by a piezoelectric ceramic-driven thermal electrospray device, had an average size of 9 µm, and also had the ability to activate the PDGFRß of NSCs more effectively than PDGF-MPH. In vitro, PDGF-MPHM exerted strong neuroprotective effects by maintaining the proliferation and inhibiting the apoptosis of NSCs in the presence of myelin extracts. In vivo, PDGF-MPHM inhibited M1 macrophage infiltration and extrinsic or intrinsic cells apoptosis on the seventh day after SCI. Eight weeks after SCI, the T10 SCI treatment results showed that PDGF-MPHM + NSCs significantly promoted the survival of NSCs and neuronal differentiation, reduced lesion size, and considerably improved motor function recovery in SCI rats by stimulating axonal regeneration, synapse formation, and angiogenesis in comparison with the NSCs graft group. Therefore, our findings provide insights into the ability of PDGF-MPHM to be a promising therapeutic agent for SCI repair.

Screw Pullout Strength After Pedicle Screw Reposition: A Finite Element Analysis.

RESEARCH DESIGN: Finite element analysis based on computed tomography images from the lumbar spine. OBJECTIVE: Determined the pullout strength of unsatisfactorily placed screws and repositioned screws after unsatisfactory place in lumbar spine surgery. BACKGROUND: Pedicle screws are widely used to stabilize the spinal vertebral body. Unsatisfactory screws could lead to surgical complications, and may need to be repositioned. Screw removal and reposition, however, may decrease pullout strength. METHODS: We conducted a three-dimensional finite element analysis based on high-resolution computed tomography images from a 39-year-old healthy woman. Pullout strength was determined with the screw placed in different orientations at the same entry point (as selected by the Magerl method), as well as after removal and reposition. The material properties of the vertebral body and the screw were simulated by using grayscale values and verified data, respectively. A load along the screw axis was applied to the end of the screw to simulate the pullout. RESULTS: The pullout strength was 1840.0 N with the Magerl method. For unsatisfactorily placed screws, the pullout strength was 1500.8 N at 20% overlap, 1609.6 N at 40% overlap, 1628.9 N at 60% overlap, and 1734.7 N at 80% overlap with the hypothetical screw path of the Magerl method. For repositioned screws, the pullout strength was 1763.6 N, with 20% overlap, 1728.3 N at 40% overlap, 1544.0 N at 60% overlap, and 1491.1 N at 80% overlap, with the original path. Comparison of repositioned screw with unsatisfactorily placed screw showed 14.04% decrease in pullout strength at 80% overlap, 5.21% decrease at 60% overlap, 7.37% increase at 40% overlap, and 17.51% increase at 20% overlap, with the screw path of the Magerl method. CONCLUSIONS: Removal and reposition increased the pullout strength at 20% and 40% overlap, but decreased the pullout strength at 60% and 80% overlap. For clinical translation, we recommend removal and reposition of the screw when the overlap is in the range of 20% to 40% or less. In vitro specimen studies are needed to verify these preliminary findings.

Thoracic Jia-Ji electro-acupuncture mitigates low skeletal muscle atrophy and improves motor function recovery following thoracic spinal cord injury in rats.

OBJECTIVES: The goal of this study was to determine whether electro-acupuncture (EA) stimulation might protect the motor endplate, minimize muscle atrophy in the hind limbs, and enhance functional recovery of rats with spinal cord injury (SCI). METHODS: Sprague-Dawley adult female rats (n = 30) were randomly assigned into Sham, SCI, and EA + SCI groups (n = 10 each). Rats in the Sham and SCI groups were bound in prone position only for 30 min, and rats in the EA + SCI group were treated with electro-acupuncture. The EA was conducted from the first day after surgery, lasted for 30 mins, once every day for 28 consecutive days. RESULTS: EA significantly prevented motor endplate degeneration, improved electrophysiological function, and ameliorated hindlimb muscle atrophy after SCI. Meanwhile, EA upregulated Tuj-1 expression, downregulated GFAP expression, and reduced glial scar formation. Additionally, after 4 weeks of EA treatment, the serum of SCI rats exhibited a reduced inflammatory response. CONCLUSION: These findings suggest that EA can preserve the motor endplate and reduce muscular atrophy. In addition, EA has been shown to improve the function of upper and lower neurons, reduce glial scar formation, suppress systemic inflammation, and improve axon regeneration.

A functionalized self-assembling peptide containing E7 and YIGSR sequences enhances neuronal differentiation of spermatogonial stem cells on aligned PCL fibers for spinal cord injury repair.

Background: Spinal cord injury (SCI) induces neuronal death and disrupts the nerve fiber bundles, which leads to partial or complete sensorimotor function loss of the limbs. Transplantation of exogenous neurons derived from stem cells to the lesion site becomes a new neurorestorative strategy for SCI treatment. Spermatogonial stem cells (SSCs) can attain pluripotency features by converting to embryonic stem-like cells in vitro. However, differentiating SSCs into lineage-specific neurons is quite difficult and low efficiency. Methods: Immunofluorescence, immunohistochemistry, Western blotting, whole-cell patch clamp, and behavioral tests were performed to verify that self-assembled hydrogels could improve the directional differentiation efficiency of SSCs and the feasibility of SSC-derived neurons in the treatment of spinal cord injury. Results: We developed a novel self-assembled peptide Nap-FFGEPLQLKMCDPGYIGSR (Nap-E7-YIGSR) coated with aligned electrospun PCL fibers to enhance neuronal differentiation of SSCs. The Nap-E7-YIGSR peptide could evenly self-assemble on the surface of PCL fibers, enhanced the materials's hydrophilicity, and improved the SSC affinity of PCL fibers through the stem cell adhesion peptide sequence EPLQLKM domain. In addition, Nap-E7-YIGSR could effectively induce SSC neuron differentiation by activating the integrin ß1/GSK3ß/ß-catenin signaling pathway. Moreover, implanting the induced neurons derived from SSCs into SCI lesion sites in rats resulted in the formation of new relay circuits, myelination, and synapse formation. Furthermore, SSC-derived neurons could survive and function in the spinal cord injury microenvironment, boosting the recovery of locomotion. Conclusion: The combination of the multifunctional peptide and aligned fibers can potentially trigger SSC differentiation to neurons, facilitating neuronal replacement therapy and promoting functional recovery after SCI.

Surgical treatment of the lower cervical brucellosis with osteoporosis in the northwest region of China: review of 22 cases.

OBJECTIVE: To analyze the surgical treatment of patients with cervical brucellosis with osteoporosis over a 4-year period in Northwest China. METHODS: From 2013 to 2018, 22 patients (12 males and 10 females) with lower cervical spine brucellosis (C3-C7) underwent anterior lesion debridement, decompression, bone grafting and internal fixation combined with posterior bone graft fusion and internal fixation (ADDF+PIF). The follow-up period averaged 37.4 months (ranging from 24 to 57 months). RESULTS: Involvement of 1 vertebra was observed in 3 patients, involvement of 3 vertebrae was observed in 9 patients, and involvement of 3 vertebrae was observed in 10 patients. Before surgery, 1 patient had Frankel grade B, 2 had grade C, 9 had grade D, and 10 had grade E. In the final follow-up, 12 patients had neurological deficits, 10 patients improved by one grade, 6 patients improved by two grades, and the neurological status of 6 patients remained unchanged. In all cases, it was observed that bone fusion required 6.8 months on average. The kyphosis Cobb angle was enhanced from an average of 11.5° preoperatively (range 0°-24°) to 0.13° postoperatively (range 1°-5°), and there was no vital loss of correction in the follow-up. CONCLUSIONS: ADDF+PIF is an effective and safe treatment for patients with lower cervical brucellosis with osteoporosis.

Global Analysis of Microbiota Signatures in Four Major Types of Gastrointestinal Cancer.

The gut microbiota has been previously linked with tumorigenesis and gastrointestinal cancer progression; however, intra-tumor microbiota analysis has just emerged and deserves increasing attention. Based on the public databases of The Cancer Microbiome Atlas (TCMA) and The Cancer Genome Atlas (TCGA), this study identified the tissue/organ microbial signatures generated from 443 biosamples of four major gastrointestinal cancer types, including esophageal carcinoma (ESCA), which further includes esophageal adenocarcinoma (EAD) and esophageal squamous cell carcinoma (ESCC), stomach adenocarcinoma (STAD), colon adenocarcinoma (COAD), and rectum adenocarcinoma (READ). According to partial least squares discrimination analysis (PLS-DA), the profile differences in microbial communities between the tumor and normal samples were not particularly noticeable across the four cancer cohorts, whereas paired comparison analyses revealed several specific differences in bacteria between tumor and normal samples in the EAD, STAD, and COAD samples. The taxa classified from the phylum to genus level revealed a trend of distinguishable microbial profiles between upper and lower gastrointestinal tumors. The Bacteroidetes/Firmicutes ratio in lower gastrointestinal tract tumors was nearly three times that in upper gastrointestinal tract tumors. We also determined the relative tissue/organ-prevalent microbes for each of the four cohorts at the order and genus levels. Microbe Alistipes, Blautia, Pasteurellales, and Porphyromonas compositions were correlated with the clinical characteristics of patients with gastrointestinal cancer, particularly colorectal cancer. Taken together, our findings indicate that microbial profiles shift across different gastrointestinal cancer types and that microbial colonization is highly site-specific. Composition of specific microbes can be indicative of cancer stage or disease progression. Overall, this study indicates that the microbial community and abundance in human tissues can be determined using publicly available data, and provides a new perspective for intra-tissue/organ microbiota research.

Safety and Efficacy of Minimally Invasive Transforaminal Lumbar Interbody Fusion Combined with Gelatin Sponge Impregnated with Dexamethasone and No Drainage Tube after Surgery in the Treatment of Lumbar Degenerative Disease.

OBJECTIVE: The aim of the present study was to use a gelatin sponge impregnated with dexamethasone, combined with minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and no drainage tube after the operation for early postoperative recurrence of root pain caused by edema. METHODS: A prospective case series study was designed. From September 2015 to January 2018, eligible patients diagnosed with lumbar degenerative disease underwent MIS-TLIF combined with a gelatin sponge impregnated with dexamethasone and no drainage tube after surgery. The short-term clinical data were collected, such as visual analog scale (VAS) scores for low back pain and leg pain preoperatively and on postoperative days (POD) 1-10, time bedridden postoperatively, and length of hospital stay postoperatively. Long-term indicators include the Japanese Orthopaedic Association (JOA) score, the Oswestry Disability Index (ODI) score, and the 36-Item Short-Form Health Survey (SF-36) score, evaluated preoperatively and 1 week, 3 months, and more than 1 year postoperatively. RESULTS: Complete clinical data was obtained for 139 patients. All patients were followed up for more than 12 months (13.7 ± 3.3 months). The average bedridden period was 1.5 ± 0.4 days and hospital stays were 2.7 ± 0.9 days. The VAS score of leg and back pain on POD 1-10 were all decreased compared with preoperation (all P < 0.0001). At the last follow up, the VAS scores for back pain and leg pain (0.69 ± 0.47; 1.02 ± 0.55) and the ODI score (11.1 ± 3.5) decreased (all P < 0.0001), and the JOA score (27.1 ± 3.2) and the SF-36 (physical component summary, 50.5 ± 7.3; mental component summary, 49.4 ± 8.9) increased (all P < 0.0001) compared with preoperative values. Patients' early and long-term levels of satisfaction postoperatively were 92.8% and 97.8%, respectively. At POD 7 and the last follow-up, the improvement rate of the JOA score, respectively, was 41.8% ± 10.6% and 87.7% ± 8.2%, and clinical effects assessed as significantly effective according to the improvement rate of the JOA score was 16.5% and 66.9%, respectively. There were 2 (1.4%) cases with complications, including 1 (0.7%) case of wound infection and 1 (0.7%) case of deep vein thrombosis. There were no device-related complications or neurological injuries. CONCLUSION: Use of a gelatin sponge impregnated with dexamethasone combined with MIS-TLIF and no drainage tube after the operation, compared with previous studies, appears to be safe and feasible to reduce recurrent back pain and leg pain after decompression in the treatment of lumbar degenerative disease.

Intraoperative anti-inflammatory drugs combined with no drainage after MIS-TLIF in the treatment of recurrent lumbar disc herniation: an RCT.

BACKGROUND: Minimally invasive-transforaminal lumbar interbody fusions (MIS-TLIF), in which the nerve root pain is caused by early postoperative edema reaction, is a common clinical complication. However, there is no effective method to solve this problem. We aimed to use gelatin sponge impregnated with mixed anti-inflammatory drugs combined with no drainage after MIS-TLIF to optimize postoperative effect in the treatment of recurrent lumbar disc herniation (LDH). METHODS: From June 2018, the middle-aged patients (45-60 years old) with recurrent LDH were recruited. Included patients were treated with MIS-TLIF surgery, and no drainage tube was placed after surgery. All patients were randomly divided into intervention group (gelatin sponge impregnated with mixed anti-inflammatory drugs) and control group (saline was immersed in gelatin sponge as a control). RESULTS: The intervention group included 63 cases, and the control group included 65 cases. The length of hospital stays and bedridden period in the intervention group were significantly lower than those in the control group (P < 0.05). The VAS score of low back pain in the intervention group was significantly lower than that of the control group at postoperative days 1-6 (P < 0.05, for all). The VAS scores of leg pain in the intervention group at postoperative days 1-9 were statistically lower than the control group (P < 0.05, for all). CONCLUSIONS: Application of gelatin sponge impregnated with mixed anti-inflammatory drugs combined with no drainage after MIS-TLIF can significantly further optimize the surgical effect of recurrent LDH and shorten the bedridden period and hospital stays, to achieve the purpose of early rehabilitation. TRIAL REGISTRATION: China Clinical Trial Registration Center, ChiCTR1800016236. Registered on May 21, 2018, http://www.chictr.org.cn/listbycreater.aspx.

Radiological and clinical differences between robotic-assisted pedicle screw fixation with and without real-time optical tracking.

OBJECTIVE: To study radiological and clinical differences between robotic-assisted pedicle screw fixation with and without real-time optical tracking. METHODS: Patients who underwent lumbar internal fixation in our hospital from June 2017 to February 2020 were divided into Tinavi group (with optical tracking) and Renaissance group (without optical tracking) according to assisted technology. The imaging data of the patients were collected, and the accuracy of screw implantation was measured according to Rampersaud A-D grade. Clinical outcomes such as operative time, fluoroscopic time and radiations dose were also collected. RESULTS: A total of 376 patients were included, including 201 patients in the Tinavi group with 968 screws implanted and 175 patients in the Renaissance group with 822 screws implanted. The accuracy of "perfect" and "clinically acceptable" pedicle screw implantation in the Tinavi group was 94.9%-98.7%, respectively, while in the Renaissance group was 91.2%-94.5%, respectively. There was significant difference between the two groups (P < 0.05). The operative time and operative time per screw in the Tinavi group were lower than those in the Renaissance group. However, fluoroscopic time per screw and radiations dose of the Tinavi group were significantly higher than those of the Renaissance group. CONCLUSION: Optical tracking in robotic system appears to increase accuracy because of the ability to detect the real-time position of the patient. Although there are still many problems to be solved, robot with optical tracking system shows its great potential in clinical application.

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.

Radiological and Clinical Differences between Tinavi Orthopedic Robot and O-Arm Navigation System in Thoracolumbar Screw Implantation for Reconstruction of Spinal Stability.

BACKGROUND Pedicle screw fixation is one of the most commonly used methods in spine surgery. We introduce a surgical robot system from China based on 3-dimensional fluoroscopy imaging and compare it with the commonly used O-arm navigation system. We study the differences in accuracy, safety, and clinical effect in auxiliary pedicle screw fixation. MATERIAL AND METHODS Patients who underwent thoracolumbar internal fixation in our hospital from 2017 to 2019 were divided into a robot and navigation group according to whether surgery was assisted by the Tinavi orthopedic robot or O-arm navigation system. Imaging data of patients were searched from the image system and accuracy of screw implantation was measured by Rampersaud A to D grade classification. Deviation sagittal, deviation transversal, and facet joint violation were also measured and calculated. RESULTS In total, 306 patients were included: 136 patients in the robot group with 760 screws implanted; 166 patients in the navigation group with 908 screws implanted. The accuracy of "perfect" and "clinically acceptable" pedicle screw implantation was 96.2% and 99.6%, respectively, in the robot group and 90.5% and 96.7%, respectively, in the navigation group, with a significant difference between the 2 groups (P<0.05). The sagittal and transversal deviations in the robot group were significantly less than those in the navigation group (P<0.05). CONCLUSIONS The Tinavi orthopedic robot can significantly improve surgical accuracy and safety of pedicle screw fixation, as compared with that of O-arm navigation technology, without increasing complications. It shows great potential in clinical application.

Reliability and application of the new morphological classification system for chronic symptomatic osteoporotic thoracolumbar fracture.

BACKGROUND: We propose a new classification system for chronic symptomatic osteoporotic thoracolumbar fracture (CSOTF) based on fracture morphology. Research on CSOTF has increased in recent years; however, the lack of a standard classification system has resulted in inconvenient communication, research, and treatment. Previous CSOTF classification studies exhibit different symptoms, with none being widely accepted. METHODS: Imaging data of 368 patients with CSOTF treated at our hospital from January 2010 to June 2017 were systematically analyzed to develop a classification system. Imaging examinations included dynamic radiography, computed tomography scans, and magnetic resonance imaging. Ten investigators methodically studied the classification system grading in 40 cases on two occasions, examined 1 month apart. Kappa coefficients (κ) were calculated to determine intraobserver and interobserver reliability. Based on the radiographic characteristics, the patients were divided into 5 types, and different treatments were suggested for each type. Clinical outcome evaluation included using the visual analog score (VAS), the Oswestry disability index (ODI), and the American Spinal Injury Association (ASIA) impairment scale. RESULTS: The new classification system for CSOTF was divided into types I-V according to whether the CSOTF exhibited dynamic instability, spinal stenosis or kyphosis deformity. Intra- and interobserver reliability were excellent for all types (κ = 0.83 and 0.85, respectively). The VAS score and ODI of each type were significantly improved at the final follow-up compared with those before surgery. In all patients with neurological impairment, the ASIA grading after surgery was significantly improved compared with that before surgery (P < 0.001). CONCLUSIONS: The new classification system for CSOTF demonstrated excellent reliability in this initial assessment. The treatment algorithm based on the classification can result in satisfactory improvement of clinical efficacy for the patients of CSOFT.

Perioperative Halo-Gravity Traction in the Treatment of Scoliosis with Intraspinal Anomalies.

OBJECTIVE: To investigate the efficacy and safety of preoperative halo-gravity traction and 1-stage posterior surgery for the treatment of scoliosis with intramedullary anomalies. METHODS: A total of 11 patients with scoliosis with intramedullary anomalies were evaluated. All patients were treated with preoperative halo-gravity traction and 1-stage posterior surgery. The average age was 11.4 years (range, 7-21 years). All patients were followed-up for at least 2 years (mean, 3.5 years; range, 2-5 years). Their radiologic presentations and complications were reviewed. RESULTS: The operating time was 7.9 hours, and the intraoperative bleeding amount was 1890 mL. Both the Cobb angle of scoliosis and kyphosis were significantly improved after halo-gravity traction and the operation (P < 0.05). Tethered cords were released, and intraspinal masses (neurofibromatosis and lipoma) were excised. Syringomyelia and split spinal cord malformations were left untreated. None of the patients experienced deterioration in their neurologic status after surgery. No severe complications, such as infection, cerebrospinal fluid leakage, failed internal fixation, or fractured pedicle screws or rods occurred after the operation. There was no deterioration of neurologic function, delayed infection, or pseudoarthrosis during the follow-up visits. CONCLUSIONS: Preoperative halo-gravity traction and 1-stage posterior surgery provided patients who had scoliosis and intramedullary anomalies an effective and safe treatment option with few complications.

[Effect of hydrogen peroxide on anti-infection and reducing postoperative drainage in multi-segmental lumbar surgery].

OBJECTIVE: To investigate the effect of hydrogen peroxide on anti-infection and reducing postoperative drainage in multi-segmental lumbar surgery. METHODS: A clinical data of 510 patients with multi-segmental lumbar degenerative diseases who were treated with surgery between January 2017 and January 2018 was retrospectively analyzed. In study group, the incisions of 230 cases were washed with hydrogen peroxide before suture. In control group, the incisions of 280 cases were washed with normal saline before suture. There was no significant difference in gender, age, lesion type, disease duration, operative segment, and other clinical data between the two groups ( P>0.05). The operation time, intraoperative blood loss, postoperative drainage volume, and postoperative incidence of infection were recorded and compared between the two groups. The Centers for Disease Control and Prevention (CDC) standard was used to evaluate infection, which was divided into superficial infection and deep infection. RESULTS: All operations completed successfully. There was no significant difference in operation time and intraoperative blood loss between the two groups ( P>0.05). The postoperative drainage volume in the study group was significantly less than that in the control group ( t=-2.990, P=0.005). A total of 13 patients developed infection after operation, including 10 cases of superficial infection (2 cases in the study group and 8 cases in the control group) with the infection time of (7.3±1.5) days, and 3 cases of deep infection (all in the control group) with the infection time of (16.6±3.1) days. The incidences of superficial and deep infections in the study group were lower than those in the control group, but there was no significant difference between the two groups ( χ 2=2.595, P=0.123; P=0.256). All the superficial infections were Staphylococcus aureus infection and recovered after active dressing change. Among the patients with deep infections, 2 cases were infected by Staphylococcus aureus and 1 case was infected by Escherichia coli; and the incisions healed after being washed and sutured thoroughly, and active dressing change. CONCLUSION: The incidence of postoperative infection and postoperative drainage volume can be reduced by washing the incision with hydrogen peroxide in multi-segmental lumbar surgery.

[A comparative study of spinal robot-assisted and traditional fluoroscopy-assisted percutaneous reduction and internal fixation for single-level thoracolumbar fractures without neurological symptoms].

OBJECTIVE: To compare the effectiveness and screw planting accuracy of percutaneous reduction and internal fixation with robot and traditional fluoroscopy-assisted in the treatment of single-level thoracolumbar fractures without neurological symptoms. METHODS: The clinical data of 58 patients with single-level thoracolumbar fractures without neurological symptoms between December 2016 and January 2018 were retrospectively analysed. According to different surgical methods, the patients were divided into group A (28 cases underwent robot-assisted percutaneous reduction and internal fixation) and group B (30 cases underwent fluoroscopy-assisted percutaneous reduction and internal fixation). There was no neurological symptoms, other fractures or organ injuries in the two groups. There was no significant difference in general data of age, gender, fracture location, AO classification, time from injury to surgery, and preoperative vertebral anterior height ratio, sagittal Cobb angle, visual analogue scale (VAS) score, and Oswestry disability index (ODI) score between the two groups ( P>0.05). The screw placement time, operation time, intraoperative blood loss, intraoperative fluoroscopy frequency, hospitalization time, operation cost, postoperative complications, VAS score, ODI score, anterior vertebral height ratio, and sagittal Cobb angle before operation, at 3 days, 6 months after operation, and at last follow-up were recorded and compared between the two groups. The accuracy of the pedicle screw placement was evaluated by Neo's criteria. RESULTS: The screw placement time, operation time, and intraoperative fluoroscopy frequency of group A were significantly less than those of group B, and the operation cost was significantly higher than that of group B ( P<0.05). But there was no significant difference in intraoperative blood loss and hospitalization time between the two groups ( P>0.05). Both groups were followed up 12-24 months, with an average of 15.2 months. The accuracy rate of screw placement in groups A and B was 93.75% (150/160) and 84.71% (144/170), respectively, and the difference was significant ( χ 2=5.820, P=0.008). Except for 1 case of postoperative superficial infection in group A and wound healing after dressing change, there was no complication such as neurovascular injury, screw loosening and fracture in both groups, and there was no significant difference in the incidence of complications between the two groups ( χ 2=0.625, P=0.547). The anterior vertebral height ratio, sagittal Cobb angle, VAS score, and ODI score of the two groups were significantly improved ( P<0.05); there was no significant difference between the two groups at all time points after operation ( P>0.05). CONCLUSION: The spinal robot and traditional fluoroscopy-assisted percutaneous reduction and internal fixation can both achieve satisfactory effectiveness in the treatment of single-level thoracolumbar fractures without neurological symptoms. However, the former has higher accuracy, fewer fluoroscopy times, shorter time of screw placement, and lower technical requirements for the operator. It has wide application potential.

Quercetin prevents necroptosis of oligodendrocytes by inhibiting macrophages/microglia polarization to M1 phenotype after spinal cord injury in rats.

BACKGROUND: Oligodendrocytes (OLs) death after spinal cord injury (SCI) contributes to demyelination, even leading to a permanent neurological deficit. Besides apoptosis, our previous study demonstrated that OLs underwent receptor-interacting serine-threonine kinase 3(RIP3)/mixed lineage kinase domain-like protein (MLKL)-mediated necroptosis. Considering that necroptosis is always accompanied with pro-inflammatory response and quercetin has long been used as anti-inflammatory agent, in the present study we investigated whether quercetin could inhibit necroptosis of OLs and suppress the M1 macrophages/microglia-mediated immune response after SCI as well as the possible mechanism. METHODS: In this study, we applied quercetin, an important flavonoid component of various herbs, to treat rats with SCI and rats injected with saline were employed as the control group. Locomotor functional recovery was evaluated using Basso-Beattie-Bresnahan (BBB) scoring and rump-height Index (RHI) assay. In vivo, the necroptosis, apoptosis, and regeneration of OLs were detected by immunohistochemistry, 5'-bromo-2'-deoxyuridine (BrdU) incorporation. The loss of myelin and axons after SCI were evaluated by Luxol fast blue (LFB) staining, immunohistochemistry, and electron microscopic study. The polarization of macrophages/microglia after SCI and the underlying mechanisms were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. In vitro, the ATP and reactive oxygen species (ROS) level examination, propidium iodide (PI) labeling, and Western blotting were used to analyze the necroptosis of cultured OLs, while the signaling pathways-mediated polarization of cultured macrophages/microglia was detected by qRT-PCR and Western blotting. RESULTS: We demonstrated that quercetin treatment improved functional recovery in rats after SCI. We then found that quercetin significantly reduced necroptosis of OLs after SCI without influencing apoptosis and regeneration of OLs. Meanwhile, myelin loss and axon loss were also significantly reduced in quercetin-treated rats, as compared to SCI + saline control. Further, we revealed that quercetin could suppress macrophages/microglia polarized to M1 phenotype through inhibition of STAT1 and NF-κB pathway in vivo and in vitro, which contributes to the decreased necroptosis of OLs. CONCLUSIONS: Quercetin treatment alleviated necroptosis of OLs partially by inhibiting M1 macrophages/microglia polarization after SCI. Our findings suggest that necroptosis of OLs may be a potential therapeutic target for clinical SCI.

Generation of functional dopaminergic neurons from human spermatogonial stem cells to rescue parkinsonian phenotypes.

BACKGROUND: Recent progress in the induced generation of dopaminergic (DA) neurons from different types of stem cells or reprogrammed somatic cells holds tremendous potential for the treatment of Parkinson's disease (PD). However, the lack of a reliable source for cell replacement therapy remains a major limitation in the treatment of human neurological disorders. Additionally, the current protocols for in vitro differentiation or cell reprogramming to generate human DA neurons are laborious, time-consuming, and expensive, and efficient conversion of human spermatogonial stem cells (hSSCs) to functional DA neurons has not yet been achieved. METHODS: Primary hSSCs from testicular tissues of patients were exposed to an improved induction system, which consisted mainly of olfactory ensheathing cell conditioned culture medium (OECCM) and a set of defined cell-extrinsic factors and small molecules. Morphological changes were assessed, along with the expression of various DA neuron phenotypic markers (e.g., Tuj-1, TH, Nurr1, DAT) and several critical pro-DA neurogenesis effectors (e.g., EN-1, Pitx3, Foxa2, Lmx1a, Lmx1b, and OTX2). In addition, transcriptome analysis was used to further evaluate the genetic similarity between the artificially differentiated DA neurons and genuine ones. Concomitantly, the functional properties of converted DA neurons including synapse formation, dopamine release, electrophysiological activity, and neuron-specific Ca2+ signaling images were determined. Finally, hSSCs in the early stage of induction were evaluated for survival, differentiation, migration, tumorigenicity in the mouse striatum, and improvement of functional deficits in MPTP-induced PD animals. RESULTS: The hSSC-derived neurons not only acquired neuronal morphological features but also expressed various phenotypic genes and protein characteristic of DA neurons and several effectors critical for pro-DA neurogenesis. Strikingly, as the period of induction was prolonged, expression of the critical molecules for DA neuron epigenetic status gradually increased while hSSC-specific markers sharply decreased. After 3 weeks of induction, the transdifferentiation efficiency reached 21%. In addition, hierarchical clustering analysis showed that the differentiated DA neurons closely resembled genuine ones. Furthermore, the hSSC-derived neurons gained sophisticated functional properties of wild-type DA neurons, and pro-induced hSSCs efficiently survived, migrated, and differentiated into DA neurons without tumorigenesis after transplantation into mouse striatum, leading to improvement of functional deficits in PD animals. CONCLUSIONS: The results showed that, using the present improved straightforward approach, hSSCs could acquire DA neuron morphological features and functional properties and rescue parkinsonian phenotypes. Our strategy for the conversion of hSSCs into DA neurons is very efficient and thus may provide an alternative approach suitable for clinical cell therapy to treat neurodegenerative diseases including PD.