Identification and verification of a novel signature that combines cuproptosis-related genes with ferroptosis-related genes in osteoarthritis using bioinformatics analysis and experimental validation.

BACKGROUND: Exploring the pathogenesis of osteoarthritis (OA) is important for its prevention, diagnosis, and treatment. Therefore, we aimed to construct novel signature genes (c-FRGs) combining cuproptosis-related genes (CRGs) with ferroptosis-related genes (FRGs) to explore the pathogenesis of OA and aid in its treatment. MATERIALS AND METHODS: Differentially expressed c-FRGs (c-FDEGs) were obtained using R software. Enrichment analysis was performed and a protein-protein interaction (PPI) network was constructed based on these c-FDEGs. Then, seven hub genes were screened. Three machine learning methods and verification experiments were used to identify four signature biomarkers from c-FDEGs, after which gene set enrichment analysis, gene set variation analysis, single-sample gene set enrichment analysis, immune function analysis, drug prediction, and ceRNA network analysis were performed based on these signature biomarkers. Subsequently, a disease model of OA was constructed using these biomarkers and validated on the GSE82107 dataset. Finally, we analyzed the distribution of the expression of these c-FDEGs in various cell populations. RESULTS: A total of 63 FRGs were found to be closely associated with 11 CRGs, and 40 c-FDEGs were identified. Bioenrichment analysis showed that they were mainly associated with inflammation, external cellular stimulation, and autophagy. CDKN1A, FZD7, GABARAPL2, and SLC39A14 were identified as OA signature biomarkers, and their corresponding miRNAs and lncRNAs were predicted. Finally, scRNA-seq data analysis showed that the differentially expressed c-FRGs had significantly different expression distributions across the cell populations. CONCLUSION: Four genes, namely CDKN1A, FZD7, GABARAPL2, and SLC39A14, are excellent biomarkers and prospective therapeutic targets for OA.

Collecting duct carcinoma with retroperitoneal mass as initial presentation: a rare case report.

BACKGROUND: Collecting duct carcinoma (CDC) is a rare renal tumor, originating from the distal collecting duct. CDC rarely presents as a primary tumor outside the renal system. CASE PRESENTATION: In this study, we report a rare case of collecting duct carcinoma, with an initial presentation of retroperitoneal lymph node metastasis, and no identifiable primary renal tumor on CT, at the time of diagnosis. The patient was a 64-year-old man presenting with lower back pain. Preoperative CT showed a round, soft tissue mass, measuring 6.7 × 4.4 × 3.3 cm, in the left retroperitoneum with no exact occupying lesion in the left kidney. Clinically, ectopic pheochromocytoma was considered to be a differential diagnosis, and tumor resection was performed. Postoperative pathological results demonstrated that the mass was a fused lymph node, and the tumor cells were destroying the structure. The final diagnosis was lymph node metastatic collecting duct carcinoma, by histology and immunohistochemistry. No further treatment was performed as no space occupying lesion was found in the kidney. Three months later, CT was reexamined, and a mass of 3.6 cm in diameter, was found in the lower left kidney, along with multiple soft tissue masses, in the left renal hilum. Considering recurrence or metastasis, the patient was recommended to undergo surgical treatment, but the patient refused. Four months later, CT was re-examined. The tumor had rapidly progressed but the patient refused treatment again. As per the author's press release (eleven months after the first discovery), the patient is still alive. CONCLUSION: CDC is a rare malignant renal carcinoma, with a high chance of rapid progress, regional lymph nodes involvement and metastasis. It presents diagnostic challenges to clinicians and pathologists, particularly, in the absence of radiographically detectable intrarenal lesions. Definite diagnosis is based on pathological examination combined with immunohistochemical staining.

Comparison of three methods for measuring C0-1 angles and C0-2 angles.

BACKGROUND: The mutual compensatory relationship between the upper cervical sagittal alignment and the lower cervical sagittal alignment has been repeatedly reported. However, the evaluation of the upper cervical sagittal parameters are varied in previous studies. This retrospective study was performed to compare three methods for measuring the upper cervical sagittal parameters. METHODS: A total of 263 individuals with standing neutral lateral cervical radiographs were included in this study. The Frankfort horizontal line (FHL), foramen magnum line (FML), and McGregor line (ML) were separately used as the reference lines for measuring the C0-1 angle and C0-2 angle. Intraclass correlation (ICC) values were used to compare the consistency and repeatability of the three methods. Pearson's correlation analysis was used to analyze the correlation between the sagittal parameters of the upper and lower cervical spine. RESULTS: The interobserver and intraobserver ICC values obtained from using the ML to measure the C0-1 angle and C0-2 angle were both higher than those obtained from using the FML or FHL. The C0-1 angle and C0-2 angle measured by the three methods were negatively correlated with the C2-7 angle. The upper sagittal parameters measured by the FHL were the most correlated with the C2-7 angle. The correlation between the C0-1 angle measured by the three methods and the C0-2 angle measured with the FHL or ML and the C2-7 angle increased with aging. CONCLUSION: Use of the ML to measure the C0-1 angle and C0-2 angle has higher reliability. Use of the FHL to measure the sagittal alignment of the upper cervical spine is more suitable for evaluating the compensation mechanism between the upper and the lower cervical spine.

Correlation between the spinopelvic type and morphological characteristics of lumbar facet joints in degenerative lumbar spondylolisthesis.

OBJECTIVE: The correlation between the spinopelvic type and morphological characteristics of lumbar facet joints in patients with degenerative lumbar spondylolisthesis (DLS) was investigated. METHODS: One hundred forty-two patients with L4 DLS were enrolled (DLS group), and 100 patients with lumbar disc herniation without DLS were selected as the control group (i.e., non-lumbar spondylolisthesis [NL] group). Morphological parameters of L4-5 facet joints and L4-5 disc height and angle were measured on 3D reconstructed CT images; namely, the facet joint angle (FJA), pedicle-facet joint angle (PFA), facet joint tropism, and facet joint osteoarthritis (OA). The L4 slip percentage, sacral slope, and lumbar lordosis were measured on radiographs. Patients in the DLS and NL groups were divided into 4 subgroups according to Roussouly classification (types I, II, III, and IV). RESULTS: In the DLS and NL groups, as the spinopelvic type changed from type II to type IV, the facet joint morphology showed a gradual sagittal orientation in the FJA, a gradual horizontal orientation in the PFA, a gradual severity in OA, and a gradual increase in the slip percentage, but changes were completely opposite from type I to type II. Additionally, compared with the NL group, the facet joint morphology in the DLS group had more horizontal orientation in PFA, more sagittal orientation in the FJA, and the facet joint tropism and OA were more severe. CONCLUSIONS: Facet joint morphology was correlated with spinopelvic type in the slip segment of DLS. Facet joint morphology was part of the joint configuration in different spinopelvic types, not just the result of joint remodeling after DLS. Moreover, morphological changes of the facet joints and DLS interacted with each other. Additionally, morphological remodeling of the facet joints in DLS played an important role in spinal balance and should be taken into consideration when designing a surgical approach.

Proteomics Reveals the Effect of Low-Intensity Focused Ultrasound on Spasticity After Spinal Cord Injury.

AIM: To explore the efficacy and possible mechanisms of Low-intensity focused ultrasound (LIFU) in alleviating spasticity caused by Spinal cord injury (SCI). MATERIAL AND METHODS: We selected male Sprague?Dawley rats as subjects and performed transverse injuries on the T9 vertebra of their spinal cord (SC) to build SCI. On the 7th day after SCI, LIFU treatment was performed below the SCI segment once a day for 20 min, for 4 consecutive weeks. During treatment, a pressure sensor was used to assess the degree of spasticity. After treatment, the SC tissues from the treatment sites of the SCI+LIFU(-) and SCI+LIFU(+) groups were extracted, and high-throughput sequencing was performed to identify the changes in proteomics. In addition, expression of the growth associated protein 43 (Gap43) was validated by western blotting. RESULTS: The behavioral results suggested that after 2 weeks of SCI, the rats were significantly induced to have a spastic reaction (p < 0.05), while after 4 weeks of LIFU treatment, the spastic response of rats was significantly improved (p < 0.05). Western blot analysis showed a significant increase in Gap43 expression in the SCI+LIFU(-) group compared with the sham group, whereas after 4 weeks of LIFU treatment, Gap43 protein expression was significantly decreased (p < 0.05). CONCLUSION: The results of this study showed that LIFU is an alternative treatment that can effectively relieve spastic reactions caused by SCI, possibly by reducing abnormal neuroplasticity or axon regeneration below the SCI segment.

Correlation Between Sacral Slope and Pedicle Morphology of the Fourth Lumbar Vertebra in Degenerative Lumbar Spondylolisthesis.

STUDY DESIGN: Retrospective Radiographic Review. OBJECTIVES: The purpose of this study was to investigate the correlation between the sacral slope (SS) and pedicle morphological parameters of the fourth lumbar vertebra in degenerative lumbar spondylolisthesis (DLS). METHODS: Our study included 134 patients with L4-5 DLS. We used preoperative multi-slice spiral computed tomography to measure a range of pedicle morphological parameters, and the SS and percentage of slip distance (SDP) of the L4 vertebra were measured on preoperative standing neutral lumbar radiography. Patients were divided into three groups based on their degree of SS: the low sacral slope (LSS) group with SS values of <35°, the mean sacral slope (MSS) group with SS of 35°-45°, and the high sacral slope (HSS) group with SS > 45°. RESULTS: As the SS increased across groups, the pedicles of L4 became longer and thinner and the pedicle camber angle was smaller. The SDP, pedicle length parameters were positively correlated with the SS, while pedicle width, height, and camber angle were negatively correlated with the SS in the three groups. CONCLUSIONS: SS had an impact on the degree of spondylolisthesis and on pedicle morphological parameters in patients with DLS, with greater slope resulting in greater impact. The progression of DLS occurred due to the increasing forward shear force of the vertebra being greater than the reverse resistance. The pedicle at the slip level adaptively remodeled, becoming slenderer and tilting inward due to the long-term traction of the two opposing forces.

Low-Intensity Focused Ultrasound Alleviates Chronic Neuropathic Pain-Induced Allodynia by Inhibiting Neuroplasticity in the Anterior Cingulate Cortex.

Low-intensity focused ultrasound (LIFU) is a potential noninvasive method to alleviate allodynia by modulating the central nervous system. However, the underlying analgesic mechanisms remain unexplored. Here, we assessed how LIFU at the anterior cingulate cortex (ACC) affects behavior response and central plasticity resulting from chronic constrictive injury (CCI). The safety of LIFU stimulation was assessed by hematoxylin and eosin (H&E) and Fluoro-Jade C (FJC) staining. A 21-day ultrasound exposure therapy was conducted from day 91 after CCI surgery in mice. We assessed the 50% mechanical withdrawal threshold (MWT50) using Von Frey filaments (VFFs). The expression levels of microtubule-associated protein 2 (MAP2), growth-associated protein 43 (GAP43), and tau were determined via western blotting (WB) and immunofluorescence (IF) staining to evaluate the central plasticity in ACC. The regions of ACC were activated effectively and safely by LIFU stimulation, which significantly increased the number of c-fos-positive cells (P < 0.05) with no bleeding, coagulative necrosis, and neuronal loss. Under chronic neuropathic pain- (CNP-) induced allodynia, MWT50 decreased significantly (P < 0.05), and overexpression of MAP2, GAP43, and tau was also observed. After 3 weeks of treatment, significant increases in MWT50 were found in the CCI+LIFU group compared with the CCI group (P < 0.05). WB and IF staining both demonstrated a significant reduction in the expression levels of MAP2, GAP43, and tau (P < 0.05). LIFU treatment on ACC can effectively attenuate CNP-evoked mechanical sensitivity to pain and reverse aberrant central plasticity.

Focused Ultrasound Promotes the Delivery of Gastrodin and Enhances the Protective Effect on Dopaminergic Neurons in a Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is the second most common chronic neurodegenerative disease globally; however, it lacks effective treatment at present. Focused ultrasound (FUS) combined with microbubbles could increase the efficacy of drug delivery to specific brain regions and is becoming a promising technology for the treatment of central nervous system diseases. In this study, we explored the therapeutic potential of FUS-mediated blood-brain barrier (BBB) opening of the left striatum to deliver gastrodin (GAS) in a subacute PD mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The concentration of GAS in the left hemisphere was detected by ultra-high performance liquid chromatography electrospray Q-Orbitrap mass spectrometry (UHPLC/ESI Q-Orbitrap) and the distribution of tyrosine hydroxylase (TH) neurons was detected by immunohistochemical staining. The expression of TH, Dopamine transporter (DAT), cleaved-caspase-3, B-cell lymphoma 2 (Bcl-2), brain-derived neurotrophic factor (BDNF), postsynaptic density protein 95 (PSD-95), and synaptophysin (SYN) protein were detected by western blotting. Analysis showed that the concentration of GAS in the left hemisphere of PD mice increased by approximately 1.8-fold after the BBB was opened. FUS-mediated GAS delivery provided optimal neuroprotective effects and was superior to the GAS or FUS control group. In addition, FUS enhanced GAS delivery significantly increased the expression of Bcl-2, BDNF, PSD-95, and SYN protein in the left striatum (P < 0.05) and reduced the levels of cleaved-caspase-3 remarkably (P = 0.001). In conclusion, the enhanced delivery by FUS effectively strengthened the protective effect of GAS on dopaminergic neurons which may be related to the reinforcement of the anti-apoptotic activity and the expression of synaptic-related proteins in the striatum. Data suggests that FUS-enhanced GAS delivery may represent a new strategy for PD treatment.

Low-Intensity Focused Ultrasound Alleviates Spasticity and Increases Expression of the Neuronal K-Cl Cotransporter in the L4-L5 Sections of Rats Following Spinal Cord Injury.

Low-intensity focused ultrasound (LIFU) has been shown to provide effective activation of the spinal cord neurocircuits. The aim of this study was to investigate the effects of LIFU in order to alleviate spasticity following spinal cord injury (SCI) by activating the spinal neurocircuits and increasing the expression of the neuronal K-Cl cotransporter KCC2. Adult male Sprague Dawley (SD) rats (220-300 g) were randomly divided into a sham control group, a LIFU- group, and a LIFU+ group. The mechanical threshold hold (g) was used to evaluate the behavioral characteristics of spasm. Electromyography (EMG) was used to assess activation of the spinal cord neurocircuits and muscle spontaneous contraction. Spasticity was assessed by frequency-dependent depression (FDD). The expression of KCC2 of the lumbar spinal cord was determined via western blot (WB) and immunofluorescence (IF) staining. The spinal cord neurocircuits were activated by LIFU simulation, which significantly reduced the mechanical threshold (g), FDD, and EMG recordings (s) after 4 weeks of treatment. WB and IF staining both demonstrated that the expression of KCC2 was reduced in the LIFU- group (P < 0.05). After 4 weeks of LIFU stimulation, expression of KCC2 had significantly increased (P < 0.05) in the LIFU+ group compared with the LIFU- group. Thus, we hypothesized that LIFU treatment can alleviate spasticity effectively and upregulate the expression of KCC2 in the L4-L5 section of SCI rats.

Treatment Combining Focused Ultrasound with Gastrodin Alleviates Memory Deficit and Neuropathology in an Alzheimer's Disease-Like Experimental Mouse Model.

Alzheimer's disease (AD) is the most common type of dementia but lacks effective treatment at present. Gastrodin (GAS) is a phenolic glycoside extracted from the traditional Chinese herb-Gastrodia elata-and has been reported as a potential therapeutic agent for AD. However, its efficiency is reduced for AD patients due to its limited BBB permeability. Studies have demonstrated the feasibility of opening the blood-brain barrier (BBB) via focused ultrasound (FUS) to overcome the obstacles preventing medicines from blood flow into the brain tissue. We explored the therapeutic potential of FUS-mediated BBB opening combined with GAS in an AD-like mouse model induced by unilateral intracerebroventricular (ICV) injection of Aß 1-42. Mice were divided into 5 groups: control, untreated, GAS, FUS and FUS+GAS. Combined treatment (FUS+GAS) rather than single intervention (GAS or FUS) alleviated memory deficit and neuropathology of AD-like mice. The time that mice spent in the novel arm was prolonged in the Y-maze test after 15-day intervention, and the waste-cleaning effect was remarkably increased. Contents of Aß, tau, and P-tau in the observed (also the targeted) hippocampus were reduced. BDNF, synaptophysin (SYN), and PSD-95 were upregulated in the combined group. Overall, our results demonstrate that FUS-mediated BBB opening combined with GAS injection exerts the potential to alleviate memory deficit and neuropathology in the AD-like experimental mouse model, which may be a novel strategy for AD treatment.

Management of fresh odontoid fractures using posterior C1-2 fixation without fusion: a long-term clinical follow-up study.

OBJECTIVE: Posterior C1-2 fixation without fusion makes it possible to restore atlantoaxial motion after removing the implant, and it has been used as an alternative technique for odontoid fractures; however, the long-term efficacy of this technique remains uncertain. The purpose of the present study was to explore the long-term follow-up outcomes of patients with odontoid fractures who underwent posterior C1-2 fixation without fusion. METHODS: A retrospective study was performed on 62 patients with type II/III fresh odontoid fractures who underwent posterior C1-2 fixation without fusion and were followed up for more than 5 years. The patients were divided into group A (23 patients with implant removal) and group B (39 patients without implant removal) based on whether they underwent a second surgery to remove the implant. The clinical outcomes were recorded and compared between the two groups. In group A, the range of motion (ROM) of C1-2 was calculated, and correlation analysis was performed to explore the factors that influence the ROM of C1-2. RESULTS: A solid fracture fusion was found in all patients. At the final follow-up, no significant difference was found in visual analog scale score or American Spinal Injury Association Impairment Scale score between the two groups (p > 0.05), but patients in group A had a lower Neck Disability Index score and milder neck stiffness than did patients in group B (p < 0.05). In group A, 87.0% (20/23) of the patients had atlantoodontoid joint osteoarthritis at the final follow-up. In group A, the C1-2 ROM in rotation was 6.1° ± 4.5° at the final follow-up, whereas the C1-2 ROM in flexion-extension was 1.8° ± 1.2°. A negative correlation was found between the C1-2 ROM in rotation and the severity of tissue injury in the atlantoaxial region (r = -0.403, p = 0.024) and the degeneration of the atlantoodontoid joint (r = -0.586, p = 0.001). CONCLUSIONS: Posterior C1-2 fixation without fusion can be used effectively for the management of fresh odontoid fractures. The removal of the implant can further improve the clinical efficacy, but satisfactory atlantoaxial motion cannot be maintained for a long time after implant removal. A surgeon should reconsider the contribution of posterior C1-2 fixation without fusion and secondary implant removal in preserving atlantoaxial mobility for patients with fresh odontoid fractures.

Effects of Noninvasive Low-Intensity Focus Ultrasound Neuromodulation on Spinal Cord Neurocircuits In Vivo.

Although neurocircuits can be activated by focused ultrasound stimulation, it is unclear whether this is also true for spinal cord neurocircuits. In this study, we used low-intensity focused ultrasound (LIFU) to stimulate lumbar 4-lumbar 5 (L4-L5) segments of the spinal cord of normal Sprague Dawley rats with a clapper. The activation of the spinal cord neurocircuits enhanced soleus muscle contraction as measured by electromyography (EMG). Neuronal activation and injury were assessed by EMG, western blotting (WB), immunofluorescence, hematoxylin and eosin (H&E) staining, Nissl staining, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry (IHC), somatosensory evoked potentials (SEPs), motor evoked potentials (MEPs), and the Basso-Beattie-Bresnahan locomotor rating scale. When the LIFU intensity was more than 0.5 MPa, LIFU stimulation induced soleus muscle contraction and increased the EMG amplitudes (P < 0.05) and the number of c-fos- and GAD65-positive cells (P < 0.05). When the LIFU intensity was 3.0 MPa, the LIFU stimulation led to spinal cord damage and decreased SEP amplitudes for electrophysiological assessment (P < 0.05); this resulted in coagulation necrosis, structural destruction, neuronal loss in the dorsal horn by H&E and Nissl staining, and increased expression of GFAP, IL-1ß, TNF-α, and caspase-3 by IHC, ELISA, and WB (P < 0.05). These results show that LIFU can activate spinal cord neurocircuits and that LIFU stimulation with an irradiation intensity ≤1.5 MPa is a safe neurostimulation method for the spinal cord.

Using a mixture of local bone dust and morselized bone as graft materials in single- and double-level ACDF.

BACKGROUND: Using a cage filled with local bone in anterior cervical discectomy and fusion (ACDF) can eliminate morbidities associated with autograft harvest from the iliac crest while achieving high fusion rates. However, there is still no consensus regarding the methods for using local bone grafts. This retrospective study was performed to compare the clinical and radiological outcomes of using a mixture of bone dust and morselized bone versus morselized bone alone in ACDF. METHODS: A retrospective study of 228 patients affected by cervical degenerative disease who had undergone single- or double-level ACDF between January 2014 and June 2018 was performed. Nanohydroxyapatite/polyamide-66 (n-HA/PA66) combined with morselized bone was used in 111 patients (group A: single-level ACDF in 51 patients and double-level ACDF in 60 patients), whereas the n-HA/PA66 cage combined with a mixture of bone dust and morselized bone was used in 117 patients (group B: single-level ACDF in 58 patients and double-level ACDF in 59 patients). The fusion rate, extent of cage subsidence, fusion segmental height (FSH), C2-7 lordosis, segmental sagittal alignment (SSA), 10-point visual analog scale (VAS) score, and Neck Disability Index (NDI) were compared between the two groups. RESULTS: The VAS score and NDI were significantly reduced after the operation in group A and group B. At the final follow-up, the fusion rate was 90.2 % (46/51) and 94.8 % (55/58) in patients treated with single-level ACDF in group A and group B, respectively (p > 0.05). In patients treated with double-level ACDF, bone fusion was achieved in 52 patients (86.7 %) in group A and 55 patients (93.2 %) in group B (p > 0.05). The fusion rate of single- and double-level ACDF was higher in patients in group B than those in group A at the 3-month, 6-month and 12-month follow-ups (p < 0.05). The extent of cage subsidence after single- and double-level ACDF was lower in patients in group B (1.5 ± 0.5 mm and 2.3 ± 0.8 mm, respectively) than in those in group A (1.8 ± 0.7 mm and 2.9 ± 1.4 mm, respectively) (p < 0.05). There was no significant difference between the two groups in the C2-7 lordosis, FSH, SSA, VAS score, or NDI before or after the operation (p > 0.05). CONCLUSIONS: Using a mixture of local bone dust and morselized bone as cage-filling materials yielded comparably good clinical outcomes as using morselized bone alone in single- and double-level ACDF. However, the mixture graft of bone dust and morselized bone was more beneficial in promoting early fusion and reducing cage subsidence.

LIFU Alleviates Neuropathic Pain by Improving the KCC2 Expression and Inhibiting the CaMKIV-KCC2 Pathway in the L4-L5 Section of the Spinal Cord.

Effective treatment remains lacking for neuropathic pain (NP), a type of intractable pain. Low-intensity focused ultrasound (LIFU), a noninvasive, cutting-edge neuromodulation technique, can effectively enhance inhibition of the central nervous system (CNS) and reduce neuronal excitability. We investigated the effect of LIFU on NP and on the expression of potassium chloride cotransporter 2 (KCC2) in the spinal cords of rats with peripheral nerve injury (PNI) in the lumbar 4-lumbar 5 (L4-L5) section. In this study, rats received PNI surgery on their right lower legs followed by LIFU stimulation of the L4-L5 section of the spinal cord for 4 weeks, starting 3 days after surgery. We used the 50% paw withdraw threshold (PWT50) to evaluate mechanical allodynia. Western blotting (WB) and immunofluorescence (IF) were used to calculate the expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), calcium/calmodulin-dependent protein kinase type IV (CaMKIV), phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB), and KCC2 in the L4-L5 portion of the spinal cord after the last behavioral tests. We found that PWT50 decreased (P < 0.05) 3 days post-PNI surgery in the LIFU- and LIFU+ groups and increased (P < 0.05) after 4 weeks of LIFU stimulation. The expression of p-CREB and CaMKIV decreased (P < 0.05) and that of KCC2 increased (P < 0.05) after 4 weeks of LIFU stimulation, but that of p-ERK1/2 (P > 0.05) was unaffected. Our study showed that LIFU could effectively alleviate NP behavior in rats with PNI by increasing the expression of KCC2 on spinal dorsal corner neurons. A possible explanation is that LIFU could inhibit the activation of the CaMKIV-KCC2 pathway.

Morphometric Analysis of the Lateral Atlantoaxial Joints in Patients with an Old Type II Odontoid Fracture and Atlantoaxial Dislocation: A Study Based on CT Analysis.

MINI: The morphological features of the lateral atlantoaxial joints (LAJs) in patients with old type II odontoid fractures and atlantoaxial dislocation have not been fully analyzed. Our study found the changes in morphological features of the LAJs in some patients, and revealed the causes and consequences of the changes in morphological features of the LAJs.

Retrospective cohort study. We aimed to study and interpret the morphological features of the lateral atlantoaxial joints (LAJs) in patients with old type II odontoid fractures and atlantoaxial dislocation (AAD). The causes and consequences of the morphological changes of the LAJs in patients with old type II odontoid fractures and AAD have not been analyzed before. A retrospective study was performed on patients with old type II odontoid fracture and AAD. These patients were placed in group A (unstable or reducible dislocation) or group B (irreducible or bony dislocation) depending on the type of dislocation they had. We documented the morphological changes and measured the inclination angle of the articular surface of the LAJs in computerized tomographic images and compared the results collected for the two groups. The association between the history of injury and the inclination angle of the articular surface of the LAJs was assessed using the Pearson correlation coefficient. A total of 29 patients were enrolled (16 patients in group A, and 13 patients in group B). The inclination angle in group A was significantly greater than that in group B ( P  < 0.001). Patients in group B were more likely to have fish-lip-like changes, dome-like changes, or collapse of the LAJs. Age, history, atlantodental interval, and Japanese Orthopedic Association score were also significant differences between the two groups ( P  < 0.05). There was a negative correlation between the history of injury and the inclination angle of the articular surfaces of the LAJs (left: r = −0.726, P  < 0.001; right: r = −0.795, P  < 0.001). The morphological changes of the LAJs could progressively become more pronounced during the evolution of the disease. Level of Evidence: 4.

Classification of the facets of lateral atlantoaxial joints in patients with congenital atlantoaxial dislocation.

PURPOSE: To investigate the morphological characteristics and para-positions of the facets of lateral atlantoaxial joints (FLAJs) in patients with congenital atlantoaxial dislocation (CAAD) and to propose a classification system for the FLAJs. METHODS: A total of 93 cases of CAAD were included in this retrospective study. The obliquity and slippage of the FLAJs in the sagittal and coronal planes were measured and observed in the CT images of all of the cases. The obliquity and slippage of the FLAJs represented the morphological characteristics and the para-positions, respectively, and were used as classification parameters. Accordingly, a classification system for the FLAJs was established. We additionally investigated the correlation between the classifications of the FLAJs and various types of CAAD. The classifications of the FLAJs in 34 patients with irreducible AAD (IAAD) were also investigated. RESULTS: One hundred eighty-six FLAJs in 93 patients were classified into 6 types (namely, A, B1, B2, C, D1, and D2) for obliquity and 3 types (namely, S0, S1, and S2) for slippage. Among the 186 FLAJs, type B1 and type S0 were the most common obliquity and slippage types, respectively. There were 11 combination types for obliquity and 5 combination types for slippage of bilateral FLAJ in 93 patients. Most of the patients (69.7%, 47/70) with anteroposterior AAD had accompanying slippage and anteversion of the FLAJ in the sagittal plane. Rotational AAD was found in 10 patients with asymmetrical slippage in both FLAJs in the sagittal plane. Lateral translational AAD was found in 6 patients with an S1-type FLAJ in the coronal plane. In 5 patients with lateral angular AAD, FLAJs of types D1 and S2 were observed on one side. Among the 34 patients with IAAD, 31 patients had both obliquity and slippage in the FLAJs on one or both sides. CONCLUSION: The morphological characteristics and para-positions of the FLAJs on both sides largely determine the types of AAD in patients with CAAD. The types of obliquity and slippage of the FLAJ are related to the reducibility of AAD.

Risk and treatment of symptomatic epidural hematoma after anterior cervical spine surgery: A retrospective clinical study.

Symptomatic epidural hematoma (SEH) after anterior cervical spine surgery is very rare, but it has disastrous consequences for the patients. Timely diagnosis and evaluation can effectively reduce the sequelae of neurological deficit in SEH. The purpose of this study was to retrospectively analyze a subset of clinical data of SEH after anterior cervical spine surgery, and to investigate the risk factors and treatment experience of this serious complication.Neurological deterioration after anterior cervical spine surgery was detected in six patients. Epidural hematoma was confirmed by emergency cervical magnetic resonance imaging (MRI). The patients included five males and one female, with an average age of 56.7 ±â€Š13.1 years (range 42-76 years). Three patients had a history of drinking and/or smoking. All of the patients were treated with nonsteroidal anti-inflammatory drugs (NSAIDs) preoperatively, but without anticoagulant drugs or pre-spinal surgery. The coagulation function was normal in all patients. Except for one patient, who had lower blood pressure (BP) during the operation and higher BP after the operation, the other patients had a normal level of BP during the pre-, intra-, and post-operation periods. The average time was 9.9 ±â€Š6.7 hours (range, 2-19 hours) from the postoperative period to the initial neurological deficit and 6.3 ±â€Š6.0 hours (range, 1.8-16.7 hours) from the initial deterioration to evacuation. Five patients underwent emergency evacuation, and one patient underwent conservative treatment. Four patients who underwent evacuation and one patient who received conservative treatment achieved neurological function recovery with an American Spinal Injury Association (ASIA) grade 2.4 ±â€Š0.9 (range, 2-4 score) score at the last follow-up. One patient with confirmed arterial epidural hemorrhage during the evaluation showed no neurological function recovery at the last follow-up.Wide exposure of the epidural space and BP level during the perioperative period play an important role in the formation of SEH after anterior cervical spine surgery. Arterial epidural hematoma has serious consequences; therefore, early diagnosis and evaluation play an important role in the recovery from paralysis.

Breast mucoepidermoid carcinoma: a case report and review of literature.

Breast mucoepidermoid carcinoma (MEC) is clinically rare, with an estimated incidence of 0.2-0.3% of all primary breast tumors. To date, only 41 cases have been reported in the literature. Herein, we present a case of breast MEC diagnosed at our hospital. The clinicopathologic features were preliminarily discussed by reviewing the literature. A 42-year-old Chinese woman presented with a lump in her right breast that was detected approximately three months prior. A microscopic examination showed that the breast MEC was composed of different proportions of mucinous cells, intermediate cells, and epidermoid cells. Most mucinous cells were positive for cytokeratin 7, while the epidermoid and intermediate cells were positive for p63 and cytokeratin 5/6. All tumor cells were negative for other myoepithelial markers, such as calponin. Tumor cells did not express estrogen, progesterone, or the HER-2/neu protein. After the patient underwent mastectomy, she was diagnosed with a low-grade mucoepidermoid carcinoma based on the clinical, histologic, and immuno-phenotypic characteristics. Our findings provide further insight into the pathologic mechanism of MEC, as correct diagnosis is essential for patient management.