Improving C1 Pedicle Screw Placement for Atlantoaxial Instability with Ultrasonic Bone Burr Assistance.

OBJECTIVE: This study aims to evaluate the safety and efficacy of the ultrasonic bone burr (UBB) in facilitating C1 pedicle screw placement for atlantoaxial instability treatment, compared to the conventional high-speed drill (HSD) technique. METHODS: A retrospective analysis was conducted on patients undergoing posterior screw-rod fixation for atlantoaxial instability between December 2017 and July 2023. The patients were divided into 2 groups based on the tools used for screw placement: UBB and HSD. Data on surgical duration, estimated blood loss, spinal cord and arterial injury incidence, screw placement accuracy, neurological status measured by the Japanese Orthopedic Association score, and fusion rates were collected and analyzed. RESULTS: Thirteen patients received C1 pedicle screw placement via UBB facilitation, while 8 were treated using the HSD approach. The UBB group showed a significant reduction in blood loss and operation time compared to the HSD group (P = 0.002 and P < 0.001, respectively). No spinal cord or arterial injuries occurred in either group. Optimal screw placement was confirmed in all UBB cases versus 87.5% in the HSD group (P = 0.139). Both groups demonstrated significant improvements in Japanese Orthopedic Association scores with no intergroup difference. The fusion rate was 100% in the UBB group and 87.5% in the HSD group, not statistically different (P = 0.381). CONCLUSIONS: UBB is a viable alternative for C1 pedicle screw placement, associated with reduced blood loss and shorter operation time, while achieving comparable clinical outcomes to the conventional HSD method. Nevertheless, further research with a larger sample size is needed.

Aberrant concordance among dynamics of spontaneous brain activity in patients with migraine without aura: A multivariate pattern analysis study.

Background: Alterations in the static and dynamic characteristics of spontaneous brain activity have been extensively studied to investigate functional brain changes in migraine without aura (MwoA). However, alterations in concordance among the dynamics of spontaneous brain activity in MwoA remain largely unknown. This study aimed to determine the possibilities of diagnosis based on the concordance indices. Methods: Resting-state functional MRI scans were performed on 32 patients with MwoA and 33 matched healthy controls (HCs) in the first cohort, as well as 36 patients with MwoA and 32 HCs in the validation cohort. The dynamic indices including fractional amplitude of low-frequency fluctuation, regional homogeneity, voxel-mirrored homotopic connectivity, degree centrality and global signal connectivity were analyzed. We calculated the concordance of grey matter volume-wise (across voxels) and voxel-wise (across time windows) to quantify the degree of integration among different functional levels represented by these dynamic indices. Subsequently, the voxel-wise concordance alterations were analyzed as features for multi-voxel pattern analysis (MVPA) utilizing the support vector machine. Results: Compared with that of HCs, patients with MwoA had lower whole-grey matter volume-wise concordance, and the mean value of volume-wise concordance was negatively correlated with the frequency of migraine attacks. The MVPA results revealed that the most discriminative brain regions were the right thalamus, right cerebellar Crus II, left insula, left precentral gyrus, right cuneus, and left inferior occipital gyrus. Conclusions: Concordance alterations in the dynamics of spontaneous brain activity in brain regions could be an important feature in the identification of patients with MwoA.

Induction of cervical disc degeneration and discogenic pain by low concentration Propionibacterium acnes infection: an in vivo animal study.

BACKGROUND: Although cervical intervertebral disc (IVD) degeneration is closely associated with neck pain, its cause remains unclear. In this study, an animal model of cervical disc degeneration and discogenic neck pain induced by a low concentration of Propionibacterium acnes (P. acnes-L) is investigated to explore the possible mechanisms of cervical discogenic pain. METHODS: Cervical IVD degeneration and discitis was induced in 8-week-old male rats in C3-C6 IVDs through the anterior intervertebral puncture with intradiscal injections of low and high concentrations of P. acnes (P. acnes-L, n = 20 and P. acnes-H, n = 15) or Staphylococcus aureus (S. aureus, n = 15), compared to control (injection with PBS, n = 20). The structural changes in the cervical IVD using micro-CT, histological evaluation, and gene expression assays after MRI scans at 2 and 6 weeks post-modeling. The P. acnes-L induced IVD degeneration model was assessed for cervical spine MRI, histological degeneration, pain-like behaviors (guarding behavior and forepaw von Frey), nerve fiber growth in the IVD endplate region, and DRG TNF-α and CGRP. RESULTS: IVD injection with P. acnes-L induced IVD degeneration with decreased IVD height and MRI T2 values. IVD injection with P. acnes-H and S. aureus both lead to discitis-like changes on T2-weighted MRI, trabecular bone remodeling on micro-CT, and osseous fusion after damage in the cartilage endplate adjacent to the injected IVD. Eventually, rats in the P. acnes-L group exhibited significant nociceptive hypersensitivity, nerve fiber ingrowth was observed in the IVD endplate region, inflammatory activity in the DRG was significantly increased compared to the control group, and the expression of the pain neurotransmitter CGRP was significantly upregulated. CONCLUSION: P. acnes-L was validated to induce cervical IVD degeneration and discogenic pain phenotype, while P. acnes-H induced was identified to resemble septic discitis comparable to those caused by S. aureus infection.

Altered effective connectivity from cerebellum to motor cortex in chronic low back pain: A multivariate pattern analysis and spectral dynamic causal modeling study.

To explore the central processing mechanism of pain perception in chronic low back pain (cLBP) using multi-voxel pattern analysis (MVPA) based on the static and dynamic fractional amplitude of low-frequency fluctuations (fALFF) analysis, and spectral dynamic causal modeling (spDCM). Thirty-two patients with cLBP and 29 matched healthy controls (HCs) for the first cohort and 24 patients with cLBP and 22 HCs for the validation cohort underwent resting-state fMRI scan. The alterations in static and dynamic fALFF were as classification features to distinguish patients with cLBP from HCs. The brain regions gotten from the MVPA results were used for further spDCM analysis. We found that the most discriminative brain regions that contributed to the classification were the right supplementary motor area (SMA.R), left paracentral lobule (PCL.L), and bilateral cerebellar Crus II. The spDCM results displayed decreased excitatory influence from the bilateral cerebellar Crus II to PCL.L in patients with cLBP compared with HCs. Moreover, the conversion of effective connectivity from the bilateral cerebellar Crus II to SMA.R from excitatory influence to inhibitive influence, and the effective connectivity strength exhibited partially mediated effects on Chinese Short Form Oswestry Disability Index Questionnaire (C-SFODI) scores. Our findings suggest that the cerebellum and its weakened or inhibited connections to the motor cortex may be one of the underlying feedback pathways for pain perception in cLBP, and partially mediate the degree of dysfunction.

Computed tomography in measuring electrode insertion angle and depth for cricopharyngeal muscle electromyography.

Background: Electromyography of the cricopharyngeal muscle (CP-EMG) is one of many assessment tools for dysphagia. The key to performing EMG and BTX injections is to precisely locate the cricopharyngeal muscle with an electrode. One of the main difficulties of electrode insertion is the fact that the CP muscle is located deep within the neck. Since a neck computed tomography (CT) can clearly display the CP muscle, thyroid, and blood vessels in the neck, we speculate that a safe concentric needle electrode insertion path to the cricopharyngeal muscle can be simulated with the assistance of the patient's neck CT which clearly marks the angle and depth of concentric needle electrode insertion. The purpose of this study was to explore simulated electrode insertion angles and insertion depths for cricopharyngeal electromyography based on retrospective CT data and present a method of percutaneous localization of the cricopharyngeal muscle based on CT images of the neck. Methods: One hundred and forty-three neck CT scans performed between January 2019 and November 2020 were included in this study. With the assistance of the angle and straight-line tools found in the Advantage Workstation 4.4 (GE, HealthCare), simulated insertion angles and depths from the anterior border of the sternocleidomastoid muscle to the cricopharyngeal muscle were obtained. Results: The 143 CT images originated from participants that included 63 males (44.1%) with an average age of 46.2±13.9 years old. The insertion angle, insertion depth, and neck thickness measured on the CT images were 53.2±10.7˚, 24.2±4.1 mm, and 130.1±17.7 mm, respectively. The insertion angle and depth were significantly greater in males than in females (P<0.05), and the insertion angle increased with the age of participants (P<0.05). A generalized linear model (GLM) showed that insertion angle was positively correlated with neck thickness (ß=0.14; 95% CI: 0.03 to 0.25) and gender (ß=5.08; 95% CI: 1.31 to 8.85), and negatively correlated with age (ß=-5.88; 95% CI: -9.54 to -1.62). Insertion depth was only positively correlated with the neck thickness (ß=0.11; 95% CI: 0.07 to 0.15). Conclusions: This study indicates that age, gender, and neck thickness are influencing factors for insertion angle, while neck thickness is the influencing factor for insertion depth. The simulated concentric needle electrode insertion method based on CT can assist clinical operation to ensure safety and effectiveness of cricopharyngeal electromyography.

Disc degeneration is easily occurred at the same and adjacent cephalad level in cervical spine when Modic changes are present.

OBJECTIVE: This research aimed to evaluate the influence of Modic changes (MCs) on disc degeneration at the same and adjacent cephalad levels in the cervical spine. METHODS: This research retrospectively reviewed 1036 patients with neck pain, upper limb pain, or numbness who were treated at our out-patient clinic and underwent cervical MRI and cervical anteroposterior/lateral radiography from Jan, 2016 to Jan, 2021. MCs and disc degeneration parameters at same and nearby cephalad levels of MCs were evaluated. Discs were divided into the MCs, adjacent, and control groups, and the association between MCs and disc degeneration at the same and adjacent cephalad levels was investigated. RESULTS: Of the 1036 patients whose MRI scans were reviewed, 986 met the inclusion criteria (503 women and 483 men; average age, 62.8 years; scope of 35-79 years). The prevalence of MCs in the cervical spine was 13.0% (128/986). Type I, II, III changes were observed in 38 (29.69%), 82 (64.06%), and 8 (6.25%) patients, respectively. MCs were most frequently identified at the C5-6 (59/986; 5.98%) and C6-7 (38/986; 3.85%) levels. Disc with MCs showed worse outcomes with regard to disc degeneration grade, anterior osteophyte formation than the adjacent and control groups (p < 0.05), whereas they were more severe in the adjacent group compared to normal group. CONCLUSION: Our findings indicate that MCs increased disc degeneration at the same and nearby cephalad levels in cervical spine, and the severity of degeneration at the same segment was more serious than that at the cephalad level.

Corrigendum: Can oblique lateral interbody fusion (OLIF) create more lumbosacral lordosis in lumbar spine surgery than minimally invasive transforaminal interbody fusion (MIS-TLIF)?

[This corrects the article DOI: 10.3389/fsurg.2022.1063354.].

Laminectomy for the Removal of Thoracic Ossification of the Ligamentum Flavum (TOLF) Using Ultrasonic and Conventional Osteotomes.

Thoracic ossification of the ligamentum flavum (TOLF) is a common cause of progressive thoracic myelopathy. TOLF is typically treated with surgical decompression. A variety of surgical techniques, including laminoplasty, laminectomy, and lamina fenestration, are used for the effective treatment of TOLF. However, traditional methods are associated with a substantial risk of perioperative complications, including dural laceration and/or iatrogenic spinal cord injury. Therefore, it is important to develop an efficient and secure surgical technique for TOLF. Herein, we describe a method for laminectomyperformed at the thoracic spine using an ultrasonic osteotome combined with a conventional osteotome. This technique can reduce intraoperative complications. This is a relatively safe and easy-to-learn method that should be recommended for the treatment of TOLF.

Emergency surgery for a patient with a thoracic spinal epidural abscess: a case report and literature review.

A man in his early 40s visited the Emergency Department because of no motor function in his lower limbs for 10 hours. Magnetic resonance imaging of his thoracic spine showed that the thoracic spinal canal (T2-T6) was occupied, and the thoracic spinal cord was compressed. In view of the severe symptoms, we quickly completed preoperative preparations and performed a thoracic laminectomy within 24 hours of paralysis of both lower limbs. Postoperatively, the patient underwent rehabilitation exercise. Four weeks later, the patient's lower limbs had full 5/5 strength. We reviewed the related literature to summarize the clinical guidelines with spinal surgeons. Timely diagnosis of thoracic spinal epidural abscess, early surgical treatment, and anti-infection management and rehabilitation exercise are essential for the full recovery of lower limb muscle strength.

[Effects of Simulated Acid Rain and Nitrogen Deposition on Soil Bacterial Community Structure and Diversity in the Masson Pine Forest].

By analyzing the effects of acid rain and nitrogen deposition on the structure and diversity of soil bacterial communities, the response mechanism of Masson pine forests to environmental stress was investigated, providing a theoretical reference basis for resource management and conservation in Tianmu Mountain National Nature Reserve. Four treatments of the simulated acid rain and nitrogen deposition were set up in 2017 to 2021 in Tianmu Mountain National Nature Reserve (pH value of 5.5 and 0 kg·(hm2·a)-1, CK; pH value of 4.5 and 30 kg·(hm2·a)-1, T1; pH value of 3.5 and 60 kg·(hm2·a)-1, T2; pH value of 2.5 and 120 kg·(hm2·a)-1, T3). The differences in soil bacterial community composition and structure among treatments and their influencing factors were analyzed by collecting soils from four treatments, using the Illumina MiSeq PE300 second-generation high-throughput sequencing platform. The results showed that acid rain and nitrogen deposition significantly reduced soil bacterial α-diversity (P<0.05) in a Masson pine forest. The Masson pine forest soils consisted of 36 phylum groups of mycota, with Acidobacteria, Proteobacteria, Actinobacteria, and Chloroflexi as the main bacterial phyla (relative abundance>1%) in the Masson pine forest soils. Flavobacterium, Nitrospira, Haliangium, Candidatus_Koribacter, Bryobacter, Occallatibacter, Acidipla, Singulisphaera, Pajaroellobacter, and Acidothermus, which showed significant changes in relative abundance under the four treatments, could be used as indicator species for changes in soil bacterial communities under acid rain and nitrogen deposition stress. Soil pH and total nitrogen were influential factors in the diversity of soil bacterial communities. As a result, acid rain and nitrogen deposition increased the potential ecological risk, and the loss of microbial diversity will change the ecosystem function as well as reduce the stability of the ecosystem.

Prediction of Single-Event Effects in FDSOI Devices Based on Deep Learning.

Single-event effects (SEE) are an important index of radiation resistance for fully depleted silicon on insulator (FDSOI) devices. The research into traditional FDSOI devices is based on simulation software, which is time consuming, requires a large amount of calculation, and has complex operations. In this paper, a prediction method for the SEE of FDSOI devices based on deep learning is proposed. The characterization parameters of SEE can be obtained quickly and accurately by inputting different particle incident conditions. The goodness of fit of the network curve for predicting drain transient current pulses can reach 0.996, and the accuracy of predicting the peak value of drain transient current and total collected charge can reach 94.00% and 96.95%, respectively. Compared with TCAD Sentaurus software, the simulation speed is increased by 5.10 × 102 and 1.38 × 103 times, respectively. This method can significantly reduce the computational cost, improve the simulation speed, and provide a new feasible method for the study of the single-event effect in FDSOI devices.

A true response of the brain network during electroacupuncture stimulation at scalp acupoints: An fMRI with simultaneous EAS study.

OBJECTIVES: The aim of this study was to explore simultaneous brain network responses to electroacupuncture stimulation (EAS) at scalp acupoints by accounting for placebo effects. MATERIALS AND METHODS: Sixty healthy subjects were recruited and randomly divided into two groups: Group 1 and Group 2. Functional magnetic resonance imaging (fMRI) was performed in Group 1 with sham acupuncture stimulation at acupoints Shenting (GV24) and Touwei (ST8) without EAS. Group 2 underwent verum EAS at the same acupoints during fMRI. Independent component analysis was used to analyze the fMRI data. Full-factor statistical analysis was used to compare the differences in fMRI data between the two groups and evaluate the changes in functional connectivity in brain networks after verum electrical stimulation (Group 1 [after sham electrical current stimulation - before sham electrical current stimulation] - Group 2 [after verum electrical current stimulation - before verum electrical current stimulation]) (p <.001, extent threshold k = 20 voxels). RESULTS: Six brain networks were identified. Significant increased functional connectivity was observed in the right and left executive control networks, sensorimotor network, and attention network, while decreased functional connectivity was mainly found in the default mode network. There were no statistically significant differences in the salience network. CONCLUSIONS: fMRI with simultaneous EAS provides a method to explore brain network responses due to EAS at scalp acupoints. The networks responsible for cognition are differentially activated by EAS in a coordinated manner.

The cumulative therapeutic effect of acupuncture in patients with migraine without aura: Evidence from dynamic alterations of intrinsic brain activity and effective connectivity.

We explored the dynamic alterations of intrinsic brain activity and effective connectivity after acupuncture treatment to investigate the underlying neurological mechanism of acupuncture treatment in patients with migraine without aura (MwoA). The Functional Magnetic Resonance Imaging (fMRI) scans were separately obtained at baseline, after the first and 12th acupuncture sessions in 40 patients with MwoA. Compared with the healthy controls (HCs), patients with MwoA mostly showed a decreased dynamic amplitude of low-frequency fluctuation (dALFF) variability in the rostral ventromedial medulla (RVM), superior lobe of left cerebellum (Cerebellum_Crus1_L), right precuneus (PCUN.R), and so on. The decreased dALFF variability of RVM, Cerebellum_Crus1_L, and PCUN.R progressively recovered after the first and 12th acupuncture treatment sessions as compared to the baseline. There was gradually increased dynamic effective connectivity (DEC) variability in RVM outflow to the right middle frontal gyrus, left insula, right precentral gyrus, and right supramarginal gyrus, and gradually enhanced DEC variability from the right fusiform gyrus inflow to RVM. Furthermore, the gradually increased DEC variability was found from Cerebellum_Crus1_L outflow to the left middle occipital gyrus and the left precentral gyrus, from PCUN.R outflow to the right thalamus. These dALFF variabilities were positively correlated with the frequency of migraine attacks and negatively correlated with disease duration at baseline. The dynamic Granger causality analysis (GCA) coefficients of this DEC variability were positively correlated with Migraine-Specific Quality of Life Questionnaire scores and negatively correlated with the frequency of migraine attacks and visual analog scale (VAS) scores after 12th acupuncture sessions. Our results were analyzed by a longitudinal fMRI in the absence of a sham acupuncture control group and provided insight into the dynamic alterations of brain activity and effective connectivity in patients with MwoA after acupuncture intervention. Acupuncture might relieve MwoA by increasing the effective connectivity of RVM, Cerebellum_Crus1_L, and PCUN.R to make up for the decreased dALFF variability in these brain areas.

Anterior cervical transpedicular screw fixation system in subaxial cervical spine: A finite element comparative study.

Multilevel cervical corpectomy has raised the concern among surgeons that reconstruction with the anterior cervical screw plate system (ACSPS) alone may fail eventually. As an alternative, the anterior cervical transpedicular screw (ACTPS) has been adopted in clinical practice. We used the finite element analysis to investigate whether ACTPS is a more reasonable choice, in comparison with ACSPS, after a 2-level corpectomy in the subaxial cervical spine. These 2 types of implantation models with the applied 75 N axial pressure and 1 N • m pure moment of the couple were evaluated. Compared with the intact model, the range of motion (ROM) at the operative segments (C4-C7) decreased by 97.5% in flexion-extension, 91.3% in axial rotation, and 99.3% in lateral bending in the ACTPS model, whereas it decreased by 95.1%, 73.4%, 96.9% in the ACSPS model respectively. The ROM at the adjacent segment (C3/4) in the ACTPS model decreased in all motions, while that of the ACSPS model increased in axial rotation and flexion-extension compared with the intact model. Compared to the ACSPS model, whose stress concentrated on the interface between the screws and the titanium plate, the stress of the ACTPS model was well-distributed. There was also a significant difference between the maximum stress value of the 2 models. ACTPS and ACSPS are biomechanically favorable. The stability in reducing ROM of ACTPS may be better and the risk of failure for internal fixator is relatively low compared with ACSPS fixation except for under lateral bending in reconstruction the stability of the subaxial cervical spine after 2-level corpectomy.

Sigma-1 receptor attenuates osteoclastogenesis by promoting ER-associated degradation of SERCA2.

Sigma-1 receptor (Sigmar1) is a specific chaperone located in the mitochondria-associated endoplasmic reticulum membrane (MAM) and plays a role in several physiological processes. However, the role of Sigmar1 in bone homeostasis remains unknown. Here, we show that mice lacking Sigmar1 exhibited severe osteoporosis in an ovariectomized model. In contrast, overexpression of Sigmar1 locally alleviated the osteoporosis phenotype. Treatment with Sigmar1 agonists impaired both human and mice osteoclast formation in vitro. Mechanistically, SERCA2 was identified to interact with Sigmar1 based on the immunoprecipitation-mass spectrum (IP-MS) and co-immunoprecipitation (co-IP) assays, and Q615 of SERCA2 was confirmed to be the critical residue for their binding. Furthermore, Sigmar1 promoted SERCA2 degradation through Hrd1/Sel1L-dependent ER-associated degradation (ERAD). Ubiquitination of SERCA2 at K460 and K541 was responsible for its proteasomal degradation. Consequently, inhibition of SERCA2 impeded Sigmar1 deficiency enhanced osteoclastogenesis. Moreover, we found that dimemorfan, an FDA-approved Sigmar1 agonist, effectively rescued bone mass in various established bone-loss models. In conclusion, Sigmar1 is a negative regulator of osteoclastogenesis, and activation of Sigmar1 by dimemorfan may be a potential treatment for osteoporosis in clinical practice.

Different responses of cervical intervertebral disc caused by low and high virulence bacterial infection: a comparative study in rats.

The aims of this study were to investigate the outcomes of low- and high-virulence bacterial cervical intervertebral discs (IVDs) infection and its association with cervical IVDs degeneration in rats. A total of 75 clean grade male rats were used to establish the corresponding animal models of low and high virulent bacterial cervical disc infection via an anterior cervical approach, with injection of Propionibacterium acnes (P. acnes) and Staphylococcus epidermidis (S. epidermidis) with a 29 G needle to cervical IVDs. Specimens were collected for evaluation of Blood routine (Blood-RT), histological staining, and gene expression assays after a magnetic resonance imaging (MRI) scan. There were no statistical differences in all groups in white blood cells (WBC) at 2 and 6 weeks postoperatively (P = 0.136). The highest percentage of neutrophils was found in the S. epidermidis group at 2 weeks postoperatively (P = 0.043). MRI and histology showed that at 6 weeks postoperatively, the puncture group and P. acnes group had similar disc degeneration. In the S. epidermidis group, the disc and subchondral bone structure had been destroyed and bony fusion had occurred after the discitis. The upregulation of pro-inflammatory factor expression had the strongest effect of S. epidermidis on the early stage, while the upregulation in the puncture and P. acnes groups was more persistent. P. acnes infection of the cervical IVDs can lead to degenerative changes, whereas S. epidermidis infection leads to the manifestation of septic discitis. The correlation between P. acnes infection and cervical IVDs degeneration found in clinical studies was confirmed.

The Changes of Brain Function After Spinal Manipulation Therapy in Patients with Chronic Low Back Pain: A Rest BOLD fMRI Study.

OBJECTIVE: To investigate the changes of regional homogeneity (Reho) values before and after spinal manipulative therapy (SMT) in patients with chronic low back pain (CLBP) through rest blood-oxygen-level-dependent functional magnetic resonance imaging (BOLD fMRI). METHODS: Patients with CLBP (Group 1, n = 20) and healthy control subjects (Group 2, n = 20) were recruited. The fMRI was performed three times in Group 1 before SMT (time point 1, TP1), after the first SMT (time point 2, TP2), after the sixth SMT (time point 3, TP3), and for one time in Group 2, which received no intervention. The clinical scales were finished in Group 1 every time before fMRI was performed. The Reho values were compared among Group 1 at different time points, and between Group 1 and Group 2. The correlation between Reho values with the statistical differences and the clinical scale scores were calculated. RESULTS: The bilateral precuneus and right mid-frontal gyrus in Group 1 had different Reho values compared with Group 2 at TP1. The Reho values were increased in the left precuneus and decreased in the left superior frontal gyrus in Group 1 at TP2 compared with TP1. The Reho values were increased in the left postcentral gyrus and decreased in the left posterior cingulate cortex and the superior frontal gyrus in Group 1 at TP3 compared with TP1. The ReHo values of the left precuneus in Group 1 at TP1 were negatively correlated with the pain degree at TP1 and TP2 (r = -0.549, -0.453; p = 0.012, 0.045). The Reho values of the middle temporal gyrus in Group 1 at TP3 were negatively correlated with the changes of clinical scale scores between TP3 and TP1 (r = 0.454, 0.559; p = 0.044, 0.01). CONCLUSION: Patients with CLBP showed abnormal brain function activity, which was altered after SMT. The Reho values of the left precuneus could predict the immediate analgesic effect of SMT.

[Establishment of finite element model of anterior cervical transpedicular system for reconstruction of cervical stability after subtotal resection of two segments of lower cervical spine].

OBJECTIVE: To establish the fixation model of anterior cervical transpedicular system (ACTPS) after subtotal resection of two segments of lower cervical spine(C3-C7) in order to provide a finite element modeling method for anterior cervical reconstruction. METHODS: The CT data of the cervical segment (C1-T1) of a 30-year-old adult healthy male volunteer was collected. Used Mimics 10.0, Rapidform XOR3, HyperMesh 10.0, CATIA5V19 and ANSYS 14.0 to establish the three-dimensional nonlinear complete model of lower cervical spine(C3-C7) as the intact group. The number of units and nodes of the complete model were recorded. After the effectiveness of the complete model was verified, the C5 and C6 vertebral subtotal resection was performed, and the ACTPS model was established as the ACTPS group. The axial force of 75 N and moment couple of 1N·m was loaded on the upper surface of C3 in intact group and ACTPS group, the range of motion(ROM)and stress distribution in states of flexion extension, lateral flexion, rotation was compared between two groups. RESULTS: There were 85 832 elements and 23 612 nodes in the complete model of lower cervical spine(C3-C7) which was established in this experiment. The stress distribution of ACTPS internal fixation model was relatively uniform. Comparing with the intact group, the overall range of motion in ACTPS group was decreased in flexion extension, lateral flexion and rotation directions, and the corresponding compensation of adjacent C3,4 segment was increased slightly. CONCLUSION: The stress distribution of ACTPS fixation system is uniform, there is no stress concentration area at the joint of screw and titanium plate, and the fracture risk of internal fixation is low. It is suitable for stability reconstruction after anterior decompression of two or more cervical segments.

Destabilization of macrophage migration inhibitory factor by 4-IPP reduces NF-κB/P-TEFb complex-mediated c-Myb transcription to suppress osteosarcoma tumourigenesis.

BACKGROUND: As an inflammatory factor and oncogenic driver protein, the pleiotropic cytokine macrophage migration inhibitory factor (MIF) plays a crucial role in the osteosarcoma microenvironment. Although 4-iodo-6-phenylpyrimidine (4-IPP) can inactivate MIF biological functions, its anti-osteosarcoma effect and molecular mechanisms have not been investigated. In this study, we identified the MIF inhibitor 4-IPP as a specific double-effector drug for osteosarcoma with both anti-tumour and anti-osteoclastogenic functions. METHODS: The anti-cancer effects of 4-IPP were evaluated by wound healing assay, cell cycle analysis, colony formation assay, CCK-8 assay, apoptosis analysis, and Transwell migration/invasion assays. Through the application of a luciferase reporter, chromatin immunoprecipitation assays, and immunofluorescence and coimmunoprecipitation analyses, the transcriptional regulation of the NF-κB/P-TEFb complex on c-Myb- and STUB1-mediated proteasome-dependent MIF protein degradation was confirmed. The effect of 4-IPP on tumour growth and metastasis was assessed using an HOS-derived tail vein metastasis model and subcutaneous and orthotopic xenograft tumour models. RESULTS: In vitro, 4-IPP significantly reduced the proliferation and metastasis of osteosarcoma cells by suppressing the NF-κB pathway. 4-IPP hindered the binding between MIF and CD74 as well as p65. Moreover, 4-IPP inhibited MIF to interrupt the formation of downstream NF-κB/P-TEFb complexes, leading to the down-regulation of c-Myb transcription. Interestingly, the implementation of 4-IPP can mediate small molecule-induced MIF protein proteasomal degradation via the STUB1 E3 ligand. However, 4-IPP still interrupted MIF-mediated communication between osteosarcoma cells and osteoclasts, thus promoting osteoclastogenesis. Remarkably, 4-IPP strongly reduced HOS-derived xenograft osteosarcoma tumourigenesis and metastasis in an in vivo mouse model. CONCLUSIONS: Our findings demonstrate that the small molecule 4-IPP targeting the MIF protein exerts an anti-osteosarcoma effect by simultaneously inactivating the biological functions of MIF and promoting its proteasomal degradation. Direct destabilization of the MIF protein with 4-IPP may be a promising therapeutic strategy for treating osteosarcoma.

A predictive model for postoperative progressive haemorrhagic injury in traumatic brain injuries.

BACKGROUND: Progressive haemorrhagic injury after surgery in patients with traumatic brain injury often results in poor patient outcomes. This study aimed to develop and validate a practical predictive tool that can reliably estimate the risk of postoperative progressive haemorrhagic injury (PHI) in patients with traumatic brain injury (TBI). METHODS: Data from 645 patients who underwent surgery for TBI between March 2018 and December 2020 were collected. The outcome was postoperative intracranial PHI, which was assessed on postoperative computed tomography. The least absolute shrinkage and selection operator (LASSO) regression model, univariate analysis, and Delphi method were applied to select the most relevant prognostic predictors. We combined conventional coagulation test (CCT) data, thromboelastography (TEG) variables, and several predictors to develop a predictive model using binary logistic regression and then presented the results as a nomogram. The predictive performance of the model was assessed with calibration and discrimination. Internal validation was assessed. RESULTS: The signature, which consisted of 11 selected features, was significantly associated with intracranial PHI (p < 0.05, for both primary and validation cohorts). Predictors in the prediction nomogram included age, S-pressure, D-pressure, pulse, temperature, reaction time, PLT, prothrombin time, activated partial thromboplastin time, FIB, and kinetics values. The model showed good discrimination, with an area under the curve of 0.8694 (95% CI, 0.8083-0.9304), and good calibration. CONCLUSION: This model is based on a nomogram incorporating CCT and TEG variables, which can be conveniently derived at hospital admission. It allows determination of this individual risk for postoperative intracranial PHI and will facilitate a timely intervention to improve outcomes.