Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury.

ABSTRACT: The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord injury. Regulation of shifting microglia polarization from M1 (neurotoxic and proinflammatory type) to M2 (neuroprotective and anti-inflammatory type) after spinal cord injury appears to be crucial. Tryptanthrin possesses an anti-inflammatory biological function. However, its roles and the underlying molecular mechanisms in spinal cord injury remain unknown. In this study, we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in vitro. Tryptanthrin promoted M2 polarization through inactivating the cGAS/STING/NF-κB pathway. Additionally, we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury, inhibited neuronal loss, and promoted tissue repair and functional recovery in a mouse model of spinal cord injury. Finally, using a conditional co-culture system, we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal apoptosis. Taken together, these results suggest that by targeting the cGAS/STING/NF-κB axis, tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.

Acacetin targets STING to alleviate the destabilization of the medial meniscus-induced osteoarthritis in mice.

Osteoarthritis (OA) is a common joint disorder affecting about 7% of the global population, primarily characterized by the gradual loss of articular cartilage. This degeneration results from local inflammation, matrix depletion, and direct cartilage damage. A critical element in this process is the activation of the stimulator of the interferon genes (STING) pathway. Emerging evidence highlights its potential as a therapeutic target, with natural products showing promise as inhibitors. Our study centers on Acacetin, a basic unit of polyketides known for its anti-inflammatory properties. Prior research has highlighted its potential interaction with STING based on the structure. Thus, this study aimed to assess the effectiveness of Acacetin as a STING inhibitor and its protective role against OA. In vitro experiments showed that Acacetin pretreatment not only mitigated interleukin-1ß (IL-1ß)-induced cytotoxicity but also decreased the inflammatory response and degeneration in chondrocytes stimulated IL-1ß. In vivo studies revealed that Acacetin administration significantly reduced articular cartilage destruction, abnormal bone remodeling, and osteophyte formation in a model of OA induced by destabilization of the medial meniscus (DMM). Mechanistically, Acacetin was found to interact directly with STING, and inhibit IL-1ß-induced activation of STING, along with the subsequent phosphorylation of the TBK1/NF-κB pathway in chondrocytes. In conclusion, our findings establish Acacetin as an effective inhibitor of STING that protects chondrocytes from IL-1ß-induced damage and slows the progression of OA in mice.

The correlation between lumbar interlaminar space size on plain radiograph and spinal stenosis.

PURPOSE: Investigating the correlation between the interlaminar space size on plain radiograph and lumbar spinal stenosis (LSS). METHODS: 100 Patients with LSS and 100 normal participants without LSS were included in this study. Lumbar interlaminar parameters were measured on plain radiographs. Spinal canal parameters were measure on CT and MRI. These image parameters were compared between LSS and control group. The linear correlation among interlaminar parameters, spinal canal parameters and Oswestry Disability Index (ODI) were analyzed. The cut-off values of interlaminar parameters for diagnosing L3/4 and L4/5 symptomatic LSS were analyzed. RESULTS: Excepting for L1/2 interlaminar width, all interlaminar and spinal canal related parameters in LSS group were significantly smaller than those in control group. Excepting for L1/2 interlaminar width and L5/S1 interlaminar height, all interlaminar parameters had significantly positive linear correlation with spinal canal parameters accordingly in each lumbar level. For diagnosis of symptomatic LSS, The cut off values of L4/5 interlaminar width, height and area were 18.46 mm, 11.37 mm and 134.05 mm2 while 15.78 mm, 13.59 mm and 157.98 mm2 in L3/4. Both spinal canal size and interlaminar size had no linear correlation with ODI in cases of L4/5 LSS. CONCLUSIONS: Lumbar interlaminar space size on plain radiograph has positive linear correlation with developmental and degenerative LSS, excepting for L1/2 interlaminar width and L5/S1 interlaminar height. Lumbar plain radiograph can be a feasible way for predicting and helping to diagnose LSS through evaluating the interlaminar space size. LEVEL OF EVIDENCE: III.

SARM1 promotes neuroinflammation and inhibits neural regeneration after spinal cord injury through NF-κB signaling.

Axonal degeneration is a common pathological feature in many acute and chronic neurological diseases such as spinal cord injury (SCI). SARM1 (sterile alpha and TIR motif-containing 1), the fifth TLR (Toll-like receptor) adaptor, has diverse functions in the immune and nervous systems, and recently has been identified as a key mediator of Wallerian degeneration (WD). However, the detailed functions of SARM1 after SCI still remain unclear. Methods: Modified Allen's method was used to establish a contusion model of SCI in mice. Furthermore, to address the function of SARM1 after SCI, conditional knockout (CKO) mice in the central nervous system (CNS), SARM1Nestin-CKO mice, and SARM1GFAP-CKO mice were successfully generated by Nestin-Cre and GFAP-Cre transgenic mice crossed with SARM1flox/flox mice, respectively. Immunostaining, Hematoxylin-Eosin (HE) staining, Nissl staining and behavioral test assays such as footprint and Basso Mouse Scale (BMS) scoring were used to examine the roles of SARM1 pathway in SCI based on these conditional knockout mice. Drugs such as FK866, an inhibitor of SARM1, and apoptozole, an inhibitor of heat shock protein 70 (HSP70), were used to further explore the molecular mechanism of SARM1 in neural regeneration after SCI. Results: We found that SARM1 was upregulated in neurons and astrocytes at early stage after SCI. SARM1Nestin-CKO and SARM1GFAP-CKO mice displayed normal development of the spinal cords and motor function. Interestingly, conditional deletion of SARM1 in neurons and astrocytes promoted the functional recovery of behavior performance after SCI. Mechanistically, conditional deletion of SARM1 in neurons and astrocytes promoted neuronal regeneration at intermediate phase after SCI, and reduced neuroinflammation at SCI early phase through downregulation of NF-κB signaling after SCI, which may be due to upregulation of HSP70. Finally, FK866, an inhibitor of SARM1, reduced the neuroinflammation and promoted the neuronal regeneration after SCI. Conclusion: Our results indicate that SARM1-mediated prodegenerative pathway and neuroinflammation promotes the pathological progress of SCI and anti-SARM1 therapeutics are viable and promising approaches for preserving neuronal function after SCI.

Early Clinical Outcomes of Percutaneous Endoscopic Lumbar Discectomy for L4-5 Highly Down-Migrated Disc Herniation: Interlaminar Approach Versus Transforaminal Approach.

OBJECTIVE: This study is a retrospective evaluation of patients with L4-5 highly down-migrated lumbar disc herniation (LDH) operated with interlaminar endoscopic lumbar discectomy (IELD) versus transforaminal endoscopic lumbar discectomy (TELD). METHODS: From January 2015 to December 2018, 77 patients with L4-5 highly down-migrated LDH were divided into 2 groups according to different surgical approaches. There were 40 patients who underwent IELD, and 37 patients who underwent TELD. The operation time, hospital stay, Oswestry Disability Index, clinical outcome according with modified MacNab criteria, Visual Analog Scale (VAS) scores, and complications were compared between the IELD and TELD groups. RESULTS: Seventy-seven patients were included, 40 and 37 patients underwent IELD and TELD, respectively. The IELD and TELD groups both achieved a significant improvement in Oswestry Disability Index, back and leg VAS scores, and clinical outcome postoperation. Mean operating and x-ray times during operation were significantly shorter in the IELD group than in the TELD group (41.8 vs. 50.3, 1.8 vs. 13.7). There were 3 patients who experienced recurrence in the IELD group and 2 in the TELD group. In the TELD group, there were 3 patients who required revision surgery due to incompletely removed disc fragment. All patients in the IELD group were treated successfully. There was no other complication in these cases. CONCLUSIONS: Both IELD and TELD could be a good alternative option for highly down-migrated LDH in L4-L5. IELD may have advantages in operation time and x-ray times during operation compared with TELD.

Creation of a planned or central-clefted puncture combined with a second puncture during vertebroplasty to treat osteoporotic vertebral compression fractures with large clefts.

BACKGROUND: Cemented vertebrae frequently re-fracture after vertebroplasty to treat osteoporotic vertebral compression fractures (OVCFs) with large clefts. We compared the efficacy of planned and central-clefted puncture, both followed by a second puncture, as treatments for OVCFs with large clefts. METHODS: We retrospectively studied 38 patients. 18 of whom underwent planned puncture (group A) and 20 central-clefted puncture (group B). A second puncture was performed when the initially injected cement was restricted to the cleft. We recorded a visual analog scale (VAS) pain scores, vertebral kyphotic angles (KAs), and compression ratios (CRs) preoperatively and at 2 days and 6 months postoperatively. We recorded the cement dispersion patterns and complications. RESULTS: Second punctures succeeded in 15/18 and 7/20 patients of groups A and B, respectively. At 2 days postoperatively, the VAS score, KA, and CR were significantly better than the preoperative values (P < 0.01); no significant difference was found between the two groups (P > 0.05). At the 6-month follow-up, all scores were poorer than at 2 days postoperatively (all P < 0.05), significantly more so in group B than group A (P < 0.05). Significant differences in terms of the cement dispersion patterns, and the cemented vertebral re-fracture and cement leakage rates, were observed between the two groups (all P < 0.05). CONCLUSION: The two-puncture techniques were initially effective when treating large-clefted OVCFs. However, compared to the central-clefted puncture, the planned puncture improved the success rate of the second puncture, allowed better cement dispersion, and reduced the incidence of vertebral re-fracture during follow-up.

Lumbar Facet Tropism on Different Facet Portions and Asymmetry Between Ipsilateral Cephalad and Caudad Portions: Their Correlations With L4/5 and L5/S1 Lumbar Disc Herniation.

STUDY DESIGN: A retrospective case-control study. OBJECTIVE: To investigate the correlation between lumbar disc herniation (LDH) and lumbar facet tropism (FT) on cephalad and caudad facet portions, respectively; to investigate the asymmetry between ipsilateral cephalad and caudad facet portions and its correlation with LDH. SUMMARY OF BACKGROUND DATA: There are still heavy debates on the exact correlation between lumbar FT and LDH. However, no study ever focused on the FT on different facet portions and asymmetry between ipsilateral cephalad and caudad portions in patients with LDH. METHODS: One hundred patients with L4/5 LDH, 100 patients with L5/S1 LDH, and 100 participants without LDH (control group) were age and sex matched and included in this study. Participants in each group were further divided into two subgroups based on age (≥ or < 50 yr old). Bilateral facet joint angles on both cephalad and caudad portions were measured. FT and asymmetry between ipsilateral cephalad and caudad portions in each LDH group were compared with those in corresponding control group. RESULTS: Comparing with control participants, the mean difference of bilateral facet angles in older patients with L4/5 LDH was significantly greater either on cephalad portion and caudad portion, whereas significantly higher frequency of FT was only exhibited on cephalad portion. In older patients with L4/5 LDH, the mean difference of facet angle between ipsilateral cephalad and caudad portions was significantly greater than that of control participants, the frequency of ipsilateral cephalad, and caudad facet asymmetry was also significantly higher. CONCLUSIONS: Only the FT on cephalad portion but not caudad portion of facet joint is associated with L4/5 LDH of older patients. The measurement on different portions of facet joint may result in discrepancy on FT identification. Asymmetry between ipsilateral cephalad and caudad facet portions is also associated with L4/5 LDH in older patients. LEVEL OF EVIDENCE: 3.

[Clinical outcomes of spinal endoscopic surgery for tiny lumbar disc herniation with severe radiating pain of lower limb].

OBJECTIVE: To study the clinical characteristics of the patients with tiny lumbar disc herniation and severe symptoms(tLDHSS) and the therapeutic effects of percutaneous endoscopic lumbar discectomy(PELD). METHODS: From January 2014 to February 2019, 34 patients with tLDHSS were reviewed retrospectively, including 20 males and 14 females, aged from 31 to 73 (48.8±10.1) years, with a follow up duration ranged from 8 to 48 (21.8±10.3) months. The clinical manifestations, imaging and surgical data were analyzed. The visual analogue scale (VAS) and Oswestry Disability Index (ODI) scores were analyzed before operation, 1 month after operation and at the latest follow-up. The preoperative and postoperativescores were compared. At the latest follow up, the Macnab system was used to evaluate the effects of the operation. RESULTS: The main symptom of 34 cases was severe radiation pain on one side of lower limbs. The duration of preoperative symptoms ranged from 0.33 to 84 months. The disc herniation was found in 7 cases of L4, 5 and 27 cases of L5S1. According to the MSU division of lumbar disc herniation, 31 cases were located in area B. In all cases, it was confirmed that the protruding nucleus compressed the nerve root, and in 26 cases, the nerve root was obviously inflamed. The operation time ranged from 30 to 80 min, with a mean time of (43.5±9.5) min. The preoperative VAS score was 8.1±1.3 and ODI score was 31.8±6.7. And the VAS score was 1.1± 0.3, 0.7±0.4 on the first month after operation and the latest follow up, respectively. The ODI score was 5.3±2.1 and 0 to 10 (with a median score of 2) on the first month after operation and the latest follow-up respectively. The postoperative VAS and ODI scores were improved compared with preoperative scores.At the latest follow up, 28 cases got an excellent result and 6 cases good according to Macnab evaluation system. During the follow-up period, only one patient had recurrent disc herniation. CONCLUSION: The main symptom of patients with tLDHSS is severe radiation pain on one side of lower limb. It manifests as sudden onset and shorter course of disease. Severe local inflammation was induced by local compression of the protruding nucleus pulposus on the nerve root out of the dura. For this kind of patients, thin layer CT scan has an important diagnostic value. In the treatment of this kind of patients, the symptoms are relieved rapidly, the curative effect is definite and the recurrence rate is low.

Astrocytic YAP Promotes the Formation of Glia Scars and Neural Regeneration after Spinal Cord Injury.

Yes-associated protein (YAP) transcriptional coactivator is negatively regulated by the Hippo pathway and functions in controlling the size of multiple organs, such as liver during development. However, it is not clear whether YAP signaling participates in the process of the formation of glia scars after spinal cord injury (SCI). In this study, we found that YAP was upregulated and activated in astrocytes of C57BL/6 male mice after SCI in a Hippo pathway-dependent manner. Conditional knockout (KO) of yap in astrocytes significantly inhibited astrocytic proliferation, impaired the formation of glial scars, inhibited the axonal regeneration, and impaired the behavioral recovery of C57BL/6 male mice after SCI. Mechanistically, the bFGF was upregulated after SCI and induced the activation of YAP through RhoA pathways, thereby promoting the formation of glial scars. Additionally, YAP promoted bFGF-induced proliferation by negatively controlling nuclear distribution of p27Kip1 mediated by CRM1. Finally, bFGF or XMU-MP-1 (an inhibitor of Hippo kinase MST1/2 to activate YAP) injection indeed activated YAP signaling and promoted the formation of glial scars and the functional recovery of mice after SCI. These findings suggest that YAP promotes the formation of glial scars and neural regeneration of mice after SCI, and that the bFGF-RhoA-YAP-p27Kip1 pathway positively regulates astrocytic proliferation after SCI.SIGNIFICANCE STATEMENT Glial scars play critical roles in neuronal regeneration of CNS injury diseases, such as spinal cord injury (SCI). Here, we provide evidence for the function of Yes-associated protein (YAP) in the formation of glial scars after SCI through regulation of astrocyte proliferation. As a downstream of bFGF (which is upregulated after SCI), YAP promotes the proliferation of astrocytes through negatively controlling nuclear distribution of p27Kip1 mediated by CRM1. Activation of YAP by bFGF or XMU-MP-1 injection promotes the formation of glial scar and the functional recovery of mice after SCI. These results suggest that the bFGF-RhoA-YAP-p27Kip1 axis for the formation of glial scars may be a potential therapeutic strategy for SCI patients.

Radiographic analysis of the correlation between ossification of the nuchal ligament and sagittal alignment and segmental stability of the cervical spine in patients with cervical spondylotic myelopathy.

BACKGROUND: Ossification of the nuchal ligament (ONL) caused by chronic injury to the nuchal ligament (NL) is very common in instability-related cervical disorders. PURPOSE: To determine possible correlations between ONL, sagittal alignment, and segmental stability of the cervical spine. MATERIAL AND METHODS: Seventy-three patients with cervical spondylotic myelopathy (CSM) and ONL (ONL group) and 118 patients with CSM only (control group) were recruited. Radiographic data included the characteristics of ONL, sagittal alignment and segmental stability, and ossification of the posterior longitudinal ligament (OPLL). We performed comparisons in terms of radiographic parameters between the ONL and control groups. The correlations between ONL size, cervical sagittal alignment, and segmental stability were analyzed. Multivariate logistic regression was used to identify the independent risk factors of the development of ONL. RESULTS: C2-C7 sagittal vertical axis (SVA), T1 slope (T1S), T1S minus cervical lordosis (T1S-CL) on the lateral plain, angular displacement (AD), and horizontal displacement (HD) on the dynamic radiograph increased significantly in the ONL group compared with the control group. The size of ONL significantly correlated with C2-C7 SVA, T1S, AD, and HD. The incidence of ONL was higher in patients with OPLL and segmental instability. Cervical instability, sagittal malalignment, and OPLL were independent predictors of the development of ONL through multivariate analysis. CONCLUSION: Patients with ONL are more likely to have abnormal sagittal alignment and instability of the cervical spine. Thus, increased awareness and appreciation of this often-overlooked radiographic finding is warranted during diagnosis and treatment of instability-related cervical pathologies and injuries.

Baicalin Induces Apoptotic Death of Human Chondrosarcoma Cells through Mitochondrial Dysfunction and Downregulation of the PI3K/Akt/mTOR Pathway.

The aim of the present study was to investigate the cytotoxic and antitumour effects of baicalin in human chondrosarcoma both in vivo and in vitro. We examined the effects of baicalin on the growth and apoptosis of human chondrosarcoma cells. Baicalin inhibited the growth of SW1353 and CH2879 cells in a dose- and time-dependent manner, but did not inhibit the growth of normal chondrocytes. Baicalin reduced tumour growth and induced apoptotic death in SW1353-transplanted nude mice without reducing their body weight. Further studies showed that baicalin reduced the mitochondrial membrane potential, upregulated the expression of Bax and cytoplasmic cytochrome c, downregulated the expression of Bcl-2 and mitochondrial cytochromes, and activated caspase-3 and caspase-9. Baicalin inhibited the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathway by decreasing the expression of phosphorylated phosphoinositide 3-kinase, phosphorylated protein kinase B, and phosphorylated mammalian target of rapamycin both in vivo and in vitro. Moreover, the mice that received SC79 and baicalin exhibited a greater tumour size compared with the mice that received baicalin. The mice that received LY294002 and baicalin showed a smaller tumour size compared with the mice that received baicalin. In the in vitro study, SC79 and LY294002 affected the baicalin-induced cytotoxic effects on chondrosarcoma cells in the same manner. Our data suggest baicalin has therapeutic efficacy in human chondrosarcoma through the induction of apoptosis and inhibition of the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin pathway. Baicalin can be considered a potential therapeutic agent for treating chondrosarcomas.

Cervical spondylotic myelopathy patients with prior cerebral infarction: Clinical characteristics, surgical outcomes and prognostic value of "prior cerebral infarction".

OBJECTIVE: To investigate the clinical characteristics and surgical outcomes of patients with cervical spondylotic myelopathy (CSM) and prior cerebral infarction (CI); to identify whether "prior CI" correlates with poor surgical outcomes. PATIENTS AND METHODS: Twenty-two patients with CSM and prior CI were retrospectively reviewed and included as the CI group while 100 CSM patients without CI were included as the control group (matched for gender, age, symptom duration and surgical approach). Extensive demographic and surgery-related data for patients in both groups were collected and compared. Multivariate logistic regression analysis was performed to assess all potential factors affecting surgical outcomes. RESULTS: Compared to the control group, the CI group had the following: significantly higher percentages of hypertension, "progressive myelopathy", "rapid progressive myelopathy" and "intramedullary T2-weighted hyperintensity on MRI"; lower mean "preoperative mJOA score" and "postoperative mJOA score"; higher percentages of "preoperative mJOA score ≤11″ and "recovery rate of mJOA score <50%". In the CI group, 14 patients had CI within 6 months before CSM, and their percentage of "rapid progressive myelopathy" was higher than that of patients who had CI over 6 months before CSM. Logistic regression analysis showed that smoking, "symptom duration ≥12 months", "T2-weighted hyperintensity" and "prior CI" correlated with poor surgical outcome. CONCLUSION: Rapid progressive myelopathy with advanced neurological impairment and "intramedullary T2-weighted hyperintensity" are common in patients with CSM and prior CI. Surgical outcomes in these patients are poorer than those of ordinary CSM patients. "Prior CI" is a risk factor for predicting poor surgical outcomes.

[Effect of the proximal level on post-laminoplasty loss of lordosis].

OBJECTIVE: To analyze the effect whether or not retaining muscle ligament complex of C2 attachment on cervical spine kyphotic deformity after single open-door laminoplasty. METHODS: A total 40 patients with cervical spondylotic myelopathy underwent single open-door laminoplasty from February 2011 to June 2014 were retrospectively analyzed. Of them, single open-door for C3-C6 was 40 cases (group A), including 28 males and 12 females, with an average age of (68.4±9.3) years old;and single open-door for C4-C6 plus C3 laminectomy decompression (in order to protect the muscle ligament complex of C2 attachment) was 40 cases (group B), including 26 males and 14 females, with an average age of (66.8±8.4) years old. Japanese Orthopaedic Association (JOA) score, visual analogue scale (VAS), Cobb angle of sagittal plane from C2-C7, cervical range of motion were used to evaluate effects before operation and at the latest follow-up. RESULTS: All the patients were followed up from 24 to 31 months with an average of(26.5±3.4) months. There was no significant differences in VAS, JOA scores and cervical range of motion before surgery between two groups (P>0.05) and all above items were significantly improved at the latest follow-up (P<0.05), but there was no significant difference between two groups(P>0.05). There was no significant difference in cervical Cobb angle before surgery between two groups(P>0.05), and postoperative Cobb angle had obviously improved in two groups(P<0.05), but the improvement of group B was better than that of group A. CONCLUSIONS: Starting the laminoplasy on C4 level and retainning the muscle ligament complex of C2 attachment can obviouly decrease cervical spine syphotic deformity.

[Application of Gemstone Spectrum Imaging for anterior spinal artery in patients with cervical spinal injury].

OBJECTIVE: To discuss the value of Gemstone Spectrum Imaging (GSI) CT anterior spinal artery angiography in the patients with cervical spinal cord injury, and to evaluate the correlation between the change of the blood flow of the anterior spinal artery and the postoperative recovery of nerve function. METHODS: From January 2014 to June 2016, thirty patients who underwent cervical open door laminoplasty for spinal cord injury were retrospective analyzed and included 21 males and 9 females with an average age of (46.4±9.7) years old ranging from 33 to 59 years. Within 2 weeks after injury, open door laminoplasty was performed through cervical posterior approach. Among them, there were 8 cases of 3 segments of open door decompression, 18 cases of 4 segments, 4 cases of 5 segments. GSI CT were performed at 3 days before operation and 5 days after operation. The anterior spinal artery was reconstructed and evaluated the improvement of blood flow after operation. The cervical JOA score was calculated at 1 day before operation, 5 days after operation and 1, 6 and 12 months after operation, and the JOA score improvement rate of the corresponding follow-up points was calculated. RESULTS: All patients were followed up for 12 to 30 months with an average of (17.4±7.6) months. The iodine content ratio (ASA/VA) of the anterior spinal artery before and after operation was 0.75±0.20 and 0.89±0.02 respectively, the postoperative improvement was significantly higher than that before operation(P<0.01). The average ASA/VA improvement rate was(21.05±12.45)% after operation. There was a positive linear correlation between the improvement of blood flow and the improvement of JOA score at 1, 6 and 12 months after operation. CONCLUSIONS: GSI CT anterior spinal artery angiography is safe and feasible, the imaging is satisfactory, it can quantitatively evaluated the blood flow of the anterior spinal artery. There was a positive linear correlation between the improvement of blood flow in anterior spinal artery and the recovery of neurological function. Early postoperative improvement of blood flow in the anterior spinal artery can be used as a reference index for predicting the recovery of neurological function in patients.

Is the Cervical Anterior Spinal Artery Compromised in Cervical Spondylotic Myelopathy Patients? Dual-Energy Computed Tomography Analysis of Cervical Anterior Spinal Artery.

OBJECTIVE: Cervical myelopathy is a common, acquired cause of spinal cord dysfunction in older patients. It is postulated that a hypoxic or ischemic environment secondary to chronic spinal cord compression plays an important role in the pathogenesis of myelopathy. This study aims to use dual-energy computed tomography (DECT) to assess the altered blood flow to the spinal cord in patients with cervical spondylotic myelopathy (CSM). To our knowledge, this study is the first to use DECT in identifying comprised anterior spinal artery blood flow in patients with CSM. METHODS: Fifty patients with single disc level CSM and 10 volunteers without CSM underwent DECT of the cervical spine to analyze and compare the ASA. The neurologic status of each patient was evaluated preoperatively and postoperatively at 5 days, 1 month, and 6 months using the Japanese Orthopedic Association (JOA) score. All the patients with CSM underwent single-level anterior cervical discectomy and fusion, and at postoperative day 5, each patient underwent repeated DECT. The anterior spinal artery before and after surgery was compared in patients with CSM. The blood flow in terms of iodine content at a specific region of interest was measured in the axial CT of the volunteers group and in the preoperative and postoperative axial CT of patients with CSM. Correlations between change in blood flow and clinical improvement at each follow-up point were analyzed statistically. RESULTS: Iodine content (100 mg/mL) was 14.2800 ± 1.89527 at the C3/C4 disc level, 14.8280 ± 1.83820 at the C4/C5 disc level, and 15.5000 ± 2.41048 at the C5/C6 level. In patients with CSM, the preoperative iodine content (100 mg/mL) measured was 10.2621 ± 2.37396 in C3/C4 disc-level compression, 12.1438 ± 1.63447 in C4/C5 disc-level compression, and 14.0620 ± 2.44390 in C5/C6 disc-level compression. Postoperative iodine content (100 mg/mL) measurement changed to 13.78 ± 2.77 for the C3/C4 disc level, 14.16 ± 1.90 for the C4/C5 disc level, and 15.14 ± 2.62 for the C5/C6 disc level. The JOA score was 13.650 preoperatively, 14.010 at 5 days postoperatively, 14.630 at 1 month postoperatively, and 15.000 at 6 months postoperatively. The 1- and 6-month correlation ratios between the JOA and change in blood flow were statistically significant, with an r value of 0.746 (P < 0.05) and 0.760 (P < 0.05), respectively. CONCLUSIONS: This study provided evidence for the benefit of DECT as a radiographic tool for identifying the compromised cervical anterior spinal artery in patients with CSM. We believe that DECT is the one of the best radiographic tools available to provide an objective screening tool to detect compromised blood flow in patients with CSM.

Early Postoperative Magnetic Resonance Imaging Findings After Percutaneous Endoscopic Lumbar Discectomy and Their Correlations with Clinical Outcomes.

OBJECTIVE: To investigate the imaging features on early postoperative magnetic resonance imaging (MRI) after percutaneous endoscopic lumbar discectomy (PELD) and their correlations with surgical outcomes. METHODS: Forty-seven patients with lumbar disc herniation who underwent PELD were enrolled in this study. MRI scans were performed 1 week and 3 months after surgery. Imaging features on these MRI scans were evaluated. Clinical factors that might affect surgical outcomes were recorded. Multivariate logistic regression analysis was performed to assess all potential factors affecting short-term and midterm outcomes after PELD. RESULTS: On MRI scans 1 week postoperatively, a residual mass at the operated site was observed in 93.6% of cases. Of those, ipsilateral nerve root compression was observed in 70.2% of cases. These residual masses had intermediate signal intensity on Tl-weighted images but either hyperintensity (56.8%) or intermediate intensity (43.2%) on T2-weighted images. On MRI scans 3 months postoperatively, the residual masses had vanished in 82.8% of cases. Based on the results of logistic regression analysis, symptom duration <1 year (P = 0.033) and high T2 signal intensity of the residual mass (P = 0.004) correlated with better short-term outcomes. However, no factor was correlated with midterm outcomes. CONCLUSIONS: A residual mass with ipsilateral nerve root compression on early postoperative MRI after PELD is common. Most of these residual masses will vanish within 3 months. "Nerve root compressed by a residual mass" on early postoperative MRI does not affect surgical outcomes. "High T2 signal intensity of the residual mass" is associated with better short-term outcomes after PELD but not midterm outcomes.

ß-Escin inhibits the proliferation of osteosarcoma cells via blocking the PI3K/Akt pathway.

ß-Escin exhibits anticancer effects on a panel of established cancer cells. However, the effects of ß-escin on human osteosarcoma (OS) are still unknown. The aim of the present study was to investigate whether ß-escin was effective against OS both in vivo and in vitro. Our results showed that ß-escin induced dose- and time-dependent effects against MG-63, OS732, U-2OS, HOS and SAOS-2 cell proliferation. ß-Escin also exhibited excellent anti-proliferative and pro-apoptotic effects in an established OS xenograft model. ß-Escin and cytotoxic drugs, including cisplatin, methotrexate (MTX), doxorubicin (Dox) and ifosfamide (Ifos), synergistically inhibited proliferation of MG-63 and OS732 cells in vitro. Moreover, ß-escin induced apoptotic death, activated caspase-3, caspase-8 and caspase-9, and regulated expression of Bax and Bcl-2 in MG-63 cells. In addition, our results showed that ß-escin treatment reduced expression of p-PI3K, p-Akt and p-mTOR both in MG-63 cells and in an MG-63 xenograft OS model. Interestingly, SC79, which is an Akt activator, inhibited the anti-proliferative effects of ß-escin on MG-63 cells. Taken together, our data support the conclusion that ß-escin effectively inhibits OS proliferation both in vivo and in vitro. The inhibitory effect of ß-escin, at least in part, is due to the inactivation of the PI3K/Akt signalling pathway.

Anterior discectomy could still be an alternative to corpectomy in highly migrated cervical disc herniation.

OBJECTIVE: For cases of cervical disc herniation, highly migrated cervical disc (HMCD) is clinically rare and usually treated with anterior cervical corpectomy and fusion (ACCF). This study aims to analyze the feasibility of anterior cervical discectomy and fusion (ACDF) for the patients with HMCD. METHOD: Clinical data of 32 patients with HMCD treated with ACDF or ACCF were retrospectively reviewed. Migration distances of the disc prolapses were measured. The mJOA score was used to evaluate surgical effect. RESULTS: ACDF was successful in 27 patients while ACCF was used for the remaining 5 because of epidural disc prolapse adhesion or unreachable migrated fragments. Complete spinal cord decompression without residual disc fragments was observed in postoperative MRI of all cases. The mean migration distance of the disc prolapses in ACDF group was 7.3 mm, comparing to 11.4 mm in ACCF group. No disc prolapse in ACDF group exceeded the axial length of the vertebral bodies while three of five in ACCF group did. Preoperative mean mJOA scores in ACDF group and ACCF group were 8.20 ± 2.75 and 6.10 ± 2.15, respectively. Postoperative mean mJOA scores in those two groups were significantly improved to 14.70 ± 1.55 (p < .001) and 12.80 ± 1.72 (p < .001), with an improvement rate of 72.80 ± 4.76% and 62.90 ± 9.46%, respectively. CONCLUSION: ACDF is feasible for patients with HMCD except for cases of epidural disc prolapse adhesion or huge disc prolapse which migrates over the axial length of the vertebral body. Clinical symptoms can be significantly improved with few serious complications in those patients including ones underwent alternative ACCF due to a failed ACDF.

Using MALDI-TOF-MS to test Staphylococcus aureus-infected vitreous.

PURPOSE: This study aimed to establish a method for testing Staphylococcus aureus in the vitreous of endophthalmitis with matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS), which is simple, fast, and sensitive. METHODS: S. aureus at different numbers was either mixed with homogenized vitreous or inoculated in porcine eyes for culturing, followed by homogenization. The homogenized vitreous samples, with or without centrifugation, were stained with Gram and Coomassie Blue (CBB) dyes and cultured with blood agar. The pellet of the vitreous mixture was analyzed with MALDI-TOF-MS. RESULTS: The minimum detectable levels of S. aureus in H2O and in the pellet of homogenized vitreous were 9.0 × 103 (positive rate, 22.2%) and 1.0 × 104 CFU/µl (positive rate, 11.1%), respectively. In the vitreous samples inoculated with S. aureus and cultured for 12 h, the number of S. aureus increased in a dose-dependent manner to the number of bacteria in the inoculate. In the supernatant of the homogenized vitreous, there were traces of bacteria identified with Gram staining. On the blood agar plates, the supernatant grew a few colonies, while the pellet grew intensive colonies. The vitreous fragments that were stained with CBB were displayed in the supernatants, in small numbers, and in the pellets. When the inoculated number was 1.0 × 104 CFU/µl or higher, the bacteria in the vitreous pellets could be identified in all samples (100%, n = 9). However, bacteria could be detected in only two out of nine spots of pellets (22.2%) if the number of inoculated S. aureus was 1.0 × 103 CFU/µl. CONCLUSIONS: A method for testing S. aureus directly from vitreous samples of endophthalmitis by the combination of easy extraction methods and a MALDI-TOF- MS assay was provided. This rapid identification method is easily adaptable for use in clinical routine and can help reduce the delay in diagnosis, allowing for earlier therapeutic intervention in patients.

[Analysis of complications of percutaneous endoscopic lumbar discectomy].

OBJECTIVE: To analyze the complications of lumbar intervertebral disc herniation treated with percutaneous endoscopic lumbar discectomy(PELD), and discuss how to avoid these complications. METHODS: The data of 132 patients with lumbar intervertebral disc herniation underwent PELD from October 2013 and June 2015 were retrospectively analyzed, including 85 males and 47 females with an average age of 42.9 years old. There were 6 cases of L3,4, 68 of L4,5 and 58 of L5S1. The incidences of intraoperative and postoperative complications were analyzed. RESULTS: There was spinal dura mater injury in 1 patient, but no cerebrospinal fluid leakage and nerve function deficit was found, the muscle strength did not decrease postoperatively and the incision healed well. Two patients converted to open surgery ultimately because of stenosis of the intervertebral foramen and adhesion between nucleus pulposus and spinal dura mater; two patients complicated with early recurrence(in 3 months);nucleus pulposus residue developed in 3 patients; all of them were treated by open surgery and got satisfactory results. One patient with heart disease history complicated with supraventricular tachycardia after surgery and 2 patients with the increased cerebrospinal fluid pressure during surgery. CONCLUSIONS: PELD have a steep learning curve, and the technology is a safe and effective method in treating lumbar disc herniation, but the beginners must have enough open surgery experience, and to grasp indications strictly.