Sarm1 is not necessary for activation of neuron-intrinsic growth programs yet required for the Schwann cell repair response and peripheral nerve regeneration.

Upon peripheral nervous system (PNS) injury, severed axons undergo rapid SARM1-dependent Wallerian degeneration (WD). In mammals, the role of SARM1 in PNS regeneration, however, is unknown. Here we demonstrate that Sarm1 is not required for axotomy induced activation of neuron-intrinsic growth programs and axonal growth into a nerve crush site. However, in the distal nerve, Sarm1 is necessary for the timely induction of the Schwann cell (SC) repair response, nerve inflammation, myelin clearance, and regeneration of sensory and motor axons. In Sarm1-/- mice, regenerated fibers exhibit reduced axon caliber, defective nerve conduction, and recovery of motor function is delayed. The growth hostile environment of Sarm1-/- distal nerve tissue was demonstrated by grafting of Sarm1-/- nerve into WT recipients. SC lineage tracing in injured WT and Sarm1-/- mice revealed morphological differences. In the Sarm1-/- distal nerve, the appearance of p75 NTR +, c-Jun+ SCs is significantly delayed. Ex vivo , p75 NTR and c-Jun upregulation in Sarm1-/- nerves can be rescued by pharmacological inhibition of ErbB kinase. Together, our studies show that Sarm1 is not necessary for the activation of neuron intrinsic growth programs but in the distal nerve is required for the orchestration of cellular programs that underlie rapid axon extension.

Neutrophil-inflicted vasculature damage suppresses immune-mediated optic nerve regeneration.

In adult mammals, injured retinal ganglion cells (RGCs) fail to spontaneously regrow severed axons, resulting in permanent visual deficits. Robust axon growth, however, is observed after intra-ocular injection of particulate ß-glucan isolated from yeast. Blood-borne myeloid cells rapidly respond to ß-glucan, releasing numerous pro-regenerative factors. Unfortunately, the pro-regenerative effects are undermined by retinal damage inflicted by an overactive immune system. Here, we demonstrate that protection of the inflamed vasculature promotes immune-mediated RGC regeneration. In the absence of microglia, leakiness of the blood-retina barrier increases, pro-inflammatory neutrophils are elevated, and RGC regeneration is reduced. Functional ablation of the complement receptor 3 (CD11b/integrin-αM), but not the complement components C1q-/- or C3-/-, reduces ocular inflammation, protects the blood-retina barrier, and enhances RGC regeneration. Selective targeting of neutrophils with anti-Ly6G does not increase axogenic neutrophils but protects the blood-retina barrier and enhances RGC regeneration. Together, these findings reveal that protection of the inflamed vasculature promotes neuronal regeneration.

Structure and function of Semaphorin-5A glycosaminoglycan interactions.

Integration of extracellular signals by neurons is pivotal for brain development, plasticity, and repair. Axon guidance relies on receptor-ligand interactions crosstalking with extracellular matrix components. Semaphorin-5A (Sema5A) is a bifunctional guidance cue exerting attractive and inhibitory effects on neuronal growth through the interaction with heparan sulfate (HS) and chondroitin sulfate (CS) glycosaminoglycans (GAGs), respectively. Sema5A harbors seven thrombospondin type-1 repeats (TSR1-7) important for GAG binding, however the underlying molecular basis and functions in vivo remain enigmatic. Here we dissect the structural basis for Sema5A:GAG specificity and demonstrate the functional significance of this interaction in vivo. Using x-ray crystallography, we reveal a dimeric fold variation for TSR4 that accommodates GAG interactions. TSR4 co-crystal structures identify binding residues validated by site-directed mutagenesis. In vitro and cell-based assays uncover specific GAG epitopes necessary for TSR association. We demonstrate that HS-GAG binding is preferred over CS-GAG and mediates Sema5A oligomerization. In vivo, Sema5A:GAG interactions are necessary for Sema5A function and regulate Plexin-A2 dependent dentate progenitor cell migration. Our study rationalizes Sema5A associated developmental and neurological disorders and provides mechanistic insights into how multifaceted guidance functions of a single transmembrane cue are regulated by proteoglycans.

Novel insights into molecular signatures and pathogenic cell populations shared by systemic lupus erythematosus and vascular dementia.

Although vascular dementia (VD) and systemic lupus erythematosus (SLE) may share immune-mediated pathophysiologic processes, the underlying mechanisms are unclear. This study investigated shared gene signatures in SLE versus VD, as well as their potential molecular mechanisms. Bulk RNA sequencing (RNAseq) and single-cell or single-nucleus RNAseq (sc/snRNAseq) datasets from SLE blood samples and VD brain samples were obtained from Gene Expression Omnibus. The identification of genes associated with both SLE and VD was performed using the weighted gene co-expression network analysis (WGCNA) and machine learning algorithms. For the sc/snRNAseq data, an unbiased clustering pipeline based on Seurat and CellChat was used to determine the cellular landscape profile and examine intracellular communication, respectively. The results were subsequently validated using a mice model of SLE with cognitive dysfunction (female MRL/lpr mice). WGCNA and machine learning identified C1QA, LY96, CD163, and MS4A4A as key genes for SLE and VD. sc/snRNAseq analyses revealed that CD163 and MS4A4A were upregulated in mononuclear phagocytes (MPs) from SLE and VD samples and were associated with monocyte-macrophage differentiation. Intriguingly, LGALS9-associated molecular pathway, as the only signaling pathway common between SLE and VD via CellChat analysis, exhibited significant upregulation in cortical microglia of MRL/lpr mice. Our analyses identified C1QA, LY96, CD163, and MS4A4A as potential biomarkers for SLE and VD. Moreover, the upregulation of CD163/MS4A4A and activation of LGALS9 signaling in MPs may contribute to the pathogenesis of VD with SLE. These findings offer novel insight into the mechanisms underlying VD in SLE patients.

[Scientific basis of acupuncture on mesenchymal stem cells for treating ischemic stroke].

The scientific basis of acupuncture on mesenchymal stem cells (MSCs) for treating ischemic stroke (IS) is discussed. MSCs transplantation has great potential for the treatment of tissue damage caused by early stage inflammatory cascade reactions of IS, but its actual transformation is limited by various factors. How to improve the homing efficiency of MSCs is the primary issue to enhance its efficacy. As such, the possible mechanisms of acupuncture and MSCs transplantation in inhibiting inflammatory cascade reactions induced by IS are explored by reviewing literature, and a hypothesis that acupuncture could promote the secretion of stromal cell-derived factor-1α (SDF-1α) from ischemic foci to regulate SDF-1α/CXC chemokine receptor 4 (CXCR4) axis, thereby improving the homing efficiency of MSCs transplantation, exerting its neuroprotective function, and improving the bed transformation ability, is proposed.

[Species, Habitat Characteristics, and Screening Suggestions of Cadmium Hyperaccumulators in China].

Phytoremediation, as a green and effective in-situ remediation technology for heavy metal-contaminated soil, has attracted the attention of Chinese scholars and has resulted in a series of achievements over the past 20 years. In this study, the species characteristics, distribution of field discovery sites in various vegetation zones, habitat characteristics, habitat geological characteristics, and geochemistry of cadmium (Cd) of the Cd hyperaccumulators in China reported in the relevant literature from the past 20 years (from 2002 to 2021) were summarized by searching for related keywords. Finally, suggestions were proposed for the screening of new Cd hyperaccumulators. The results showed that a total of 45 species of Cd hyperaccumulators in China have been reported so far. In terms of plant species, they belonged to 22 families and 36 genera, among which Compositae with 14 species was the most abundant. There were 25 species discovered through the field investigation, which were mainly distributed in the subtropical broadleaf evergreen forest region of southern China. Additionally, the Cd hyperaccumulators discovered by field surveys were mainly found in high Cd-concentrated soils surrounding lead-zinc mines. In conclusion, abundant plant resources, high concentrations of heavy metal soils, and long-term domestication jointly promoted the formation of hyperaccumulators. Therefore, the region with these three points could be considered a high probability region for the presence of hyperaccumulators, and the screening of hyperaccumulators could be carried out around this. We proposed that the screening of new hyperaccumulators can be carried out through the following six steps:the identification and investigation of high probability areas, the enrichment capability test, the enrichment capability test in low concentration levels, the enrichment capability test between different ecotypes, the succession of enrichment capability, and the test of remediation proficiency.

Lumbar Intradural Disc Herniation Caused by Injury: A Case Report and Literature Review.

BACKGROUND: Intradural disc herniation(IDH) caused by trauma is a rare type of disease，which is difficult to diagnose clinically and is easily misdiagnosed. We received a patient with the disease, reported the case to share the process of diagnosis and treatment and put forward our own opinions, so as to increase the probability of correct diagnosis. CASE PRESENTATION: We report the case of a 48-year-old male who fell from a scaffold at a height of 2 m. Later, he developed low back pain, restricted movement, numbness and hyperalgesia of the lower left limb, and decreased left muscle strength. He was diagnosed with IDH. Treatment with posterior decompression and intramedullary decompression with pedicle screw internal fixation was performed. His postoperative course was uneventful, and he underwent regular follow up for 1 year. Good neurologic symptom improvement was achieved. CONCLUSIONS: IDH is rare, and comprehensive consideration and film reading can improve the correct diagnosis rate. Accurate diagnosis and early decompression of laminae and intramedullary decompression can lead to good recovery after neurologic impingement.

Identifying spatial agglomeration and driving forces of land use by green industries: a case study of Jiangsu Province, China.

In response to China's aims of becoming "carbon-neutral," the development of green industries such as renewable energy and recycling has flourished. Based on 2015 and 2019 data, this study uses spatial autocorrelation to analyze the evolution of land use by the green industries in Jiangsu Province. The Geodetector model was also applied to identify the driving factors underlying these spatial patterns. The spatial variability of green industrial land use in Jiangsu Province is significant, with the land-use area gradually decreasing from Southern to Northern Jiangsu. In terms of spatial-temporal changes, there is an increase in land use and a trend of expansion in the central and northern regions of Jiangsu. Land use by green industries in the province exhibits a more significant spatial clustering pattern but with a weakened clustering effect. The clustering types are mainly H-H and L-L, with the H-H type distributed mainly in the Su-Xi-Chang region and the L-L type distributed mainly in the Northern Jiangsu region. The levels of technology, economic development, industrialization, and industrial diversification are important individual driving factors, and the interaction among the different factors enhances their driving forces. This study suggests that spatial spillover effects should be focused to promote the coordinated development of regional energy-saving and environmental protection industries. At the same time, joint efforts should be made from the aspects of resources, government, economy, and related industries to promote the agglomeration of land for energy-saving and environmental protection industries.

Clinical Efficacy Analysis of the New PRUNUS Spine Plate System for Anterior Cervical Spine Surgery.

OBJECTIVE: Although the role of anterior cervical titanium plate system in stabilizing the spine sequence and promoting bone graft fusion has been widely recognized, more and more attention has been paid to the design of the plate itself and the complications caused by it. In order to solve the problems of poor stability of internal fixation, plate displacement and screw looseness, we designed the new PRUNUS spine plate system. Hence, the present study was conducted to describe observe and evaluate the clinical efficacy of a new type of three-leaf reinforced cervical anterior screw plate system (PRUNUS nailing system) developed for anterior cervical surgery. METHODS: A retrospective analysis of 56 patients from June 2018 to October 2019 was used. Twenty-seven patients with cervical spine disease treated with new PRUNUS nail plate internal fixation were selected as the observation group, and 29 patients with cervical spine disease treated with conventional cervical anterior screw fixation were selected as the control group. Postoperative follow-up was performed. Cervical stability, internal fixation position and bone graft fusion were evaluated according to imaging data. The operative time, intraoperative blood loss, cervical Cobb angle, pain visual analogue scale (VAS), and Japanese orthopaedic association (JOA) were compared between the two groups. Spinal function scores and neurological improvement rates were used to evaluate the clinical efficacy of the new PRUNUS spine plate. RESULTS: The patients were followed up for 5-18 months, with an average of 7.33 months. The average operative time of the observation group was 98.4 ± 9.2 min, and the mean intraoperative blood loss was 65.3 ± 10.6 ml, which were significant different from the control group's 109.7 ± 9.4 minutes (P < 0.05), 72.9 ± 15.6 ml (P < 0.05). Comparison between the two groups in postoperative and final follow-up of cervical Cobb angle, JOA score and improvement rate, VAS score and preoperative comparison showed no significant differences (P > 0.05). CONCLUSION: The new PRUNUS spine plate system can be applied to the anterior cervical spine surgery, and its clinical efficacy was similar to the traditional cervical anterior plate. But PRUNUS simplified the operation process, especially suitable for the surgical treatment of anterior cervical revision and osteoporosis patients.

The injured sciatic nerve atlas (iSNAT), insights into the cellular and molecular basis of neural tissue degeneration and regeneration.

Upon trauma, the adult murine peripheral nervous system (PNS) displays a remarkable degree of spontaneous anatomical and functional regeneration. To explore extrinsic mechanisms of neural repair, we carried out single-cell analysis of naïve mouse sciatic nerve, peripheral blood mononuclear cells, and crushed sciatic nerves at 1 day, 3 days, and 7 days following injury. During the first week, monocytes and macrophages (Mo/Mac) rapidly accumulate in the injured nerve and undergo extensive metabolic reprogramming. Proinflammatory Mo/Mac with a high glycolytic flux dominate the early injury response and rapidly give way to inflammation resolving Mac, programmed toward oxidative phosphorylation. Nerve crush injury causes partial leakiness of the blood-nerve barrier, proliferation of endoneurial and perineurial stromal cells, and entry of opsonizing serum proteins. Micro-dissection of the nerve injury site and distal nerve, followed by single-cell RNA-sequencing, identified distinct immune compartments, triggered by mechanical nerve wounding and Wallerian degeneration, respectively. This finding was independently confirmed with Sarm1-/- mice, in which Wallerian degeneration is greatly delayed. Experiments with chimeric mice showed that wildtype immune cells readily enter the injury site in Sarm1-/- mice, but are sparse in the distal nerve, except for Mo. We used CellChat to explore intercellular communications in the naïve and injured PNS and report on hundreds of ligand-receptor interactions. Our longitudinal analysis represents a new resource for neural tissue regeneration, reveals location- specific immune microenvironments, and reports on large intercellular communication networks. To facilitate mining of scRNAseq datasets, we generated the injured sciatic nerve atlas (iSNAT): https://cdb-rshiny.med.umich.edu/Giger_iSNAT/.

Retrorectal mucinous adenocarcinoma arising from a tailgut cyst: A case report and review of literature.

BACKGROUND: Tailgut cysts are defined as congenital cysts that develop in the rectosacral space from the residue of the primitive tail. As a congenital disease, caudal cysts are very rare, and their canceration is even rarer, which makes the disease prone to misdiagnosis and delayed treatment. We describe a case of caudal cyst with adenocarcinogenesis and summarize in detail the characteristics of cases with analytical value reported since 1990. CASE SUMMARY: A 35-year-old woman found a mass in her lower abdomen 2 mo ago. She was asymptomatic at that time and was not treated because of the coronavirus disease 2019 pandemic. Two weeks ago, the patient developed abdominal distension and right waist discomfort and came to our hospital. Except for the high level of serum carcinoembryonic antigen, the medical history and laboratory tests were not remarkable. Magnetic resonance imaging showed a well-defined, slightly lobulated cystic-solid mass with a straight diameter of approximately 10 cm × 9 cm in the presacral space, slightly high signal intensity on T2-weighted imaging, and moderate signal intensity on T1-weighted imaging. The mass was completely removed by laparoscopic surgery. Histopathological examination showed that the lesion was an intestinal mucinous adenocarcinoma, and the multidisciplinary team decided to implement postoperative chemotherapy. The patient recovered well, the tumor marker levels returned to normal, and tumor-free survival has been achieved thus far. CONCLUSION: The case and literature summary can help clinicians and researchers develop appropriate examination and therapeutic methods for diagnosis and treatment of this rare disease.

Plexins promote Hedgehog signaling through their cytoplasmic GAP activity.

Hedgehog signaling controls tissue patterning during embryonic and postnatal development and continues to play important roles throughout life. Characterizing the full complement of Hedgehog pathway components is essential to understanding its wide-ranging functions. Previous work has identified neuropilins, established semaphorin receptors, as positive regulators of Hedgehog signaling. Neuropilins require plexin co-receptors to mediate semaphorin signaling, but the role of plexins in Hedgehog signaling has not yet been explored. Here, we provide evidence that multiple plexins promote Hedgehog signaling in NIH/3T3 mouse fibroblasts and that plexin loss of function in these cells results in significantly reduced Hedgehog pathway activity. Catalytic activity of the plexin GTPase-activating protein (GAP) domain is required for Hedgehog signal promotion, and constitutive activation of the GAP domain further amplifies Hedgehog signaling. Additionally, we demonstrate that plexins promote Hedgehog signaling at the level of GLI transcription factors and that this promotion requires intact primary cilia. Finally, we find that plexin loss of function significantly reduces the response to Hedgehog pathway activation in the mouse dentate gyrus. Together, these data identify plexins as novel components of the Hedgehog pathway and provide insight into their mechanism of action.

Migrating pyramidal neurons require DSCAM to bypass the border of the developing cortical plate.

During mammalian neocortex development, nascent pyramidal neurons migrate along radial glial cells and overtake earlier-born neurons to terminate at the front of the developing cortical plate (CP), leading to the outward expansion of the CP border. While much has been learned about the cellular and molecular mechanisms that underlie the migration of pyramidal neurons, how migrating neurons bypass the preceding neurons at the end of migration to reach their final positions remains poorly understood. Here, we report that Down syndrome cell adhesion molecule (DSCAM) is required for migrating neurons to bypass their post-migratory predecessors during the expansion of the upper cortical layers. DSCAM is a type I transmembrane cell adhesion molecule. It has been linked to Down syndrome through its location in the Down syndrome critical region of Chromosome 21 trisomy and to autism spectrum disorders through loss-of-function mutations. Ex vivo time-lapse imaging demonstrates that DSCAM is required for migrating neurons to bypass their post-migratory predecessors, crossing the CP border to expand the upper cortical layers. In DSCAM-deficient cortices, migrating neurons stop prematurely under the CP border, leading to thinner and denser upper cortical layers. We further show that DSCAM weakens cell adhesion mediated by N-cadherin in the upper cortical plate, allowing migrating neurons to traverse the CP border and expand the CP. These findings suggest that DSCAM is required for proper migratory termination and final positioning of nascent pyramidal neurons, which may provide insight into brain disorders that exhibit thinner upper layers of the cerebral cortex without neuronal loss.SIGNIFICANCE STATEMENTNewly born neurons in the developing mammalian neocortex migrate outward towards the cortical surface, bypassing earlier born neurons to expand the developing cortex. How migrating neurons bypass the preceding neurons and terminate at the front of the expanding cortex remains poorly understood. We demonstrate that Down syndrome cell adhesion molecule (DSCAM), linked to Down syndrome and autism spectrum disorder, is required by migrating neurons to bypass their post-migratory predecessors and terminate migration in the outwardly expanding cortical layer. Migrating neurons deficient in DSCAM stop prematurely, failing to expand the cortex. We further show that DSCAM likely mediates migratory termination by weakening cell-adhesion mediated by N-cadherin.

Inhibition of Liver Cancer HepG2 Cell Proliferation by Enzymatically Prepared Low-molecular Citrus Pectin.

BACKGROUND: Low-molecular citrus pectin (LCP) is a pectin polysaccharide with low molec-ular weight, low degree of crux, and no branching. It is obtained by degrading natural citrus pectin (CP) through physical, chemical and enzymatic methods. LCP has received considerable attention in recent years due to its potential applications in the medical and biological fields. METHODS: In our previous study, LCP was prepared from CP by using recombinant Bacillus subtilis pectate lyase B. Monosaccharide comparative analysis revealed that the galacturonic acid content of LCP was higher than that of CP. The cell viability effect of LCP was elucidated by using HepG2 cells and the Cell Counting Kit-8 (CCK-8) assay. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining, Annexin V-FITC/PI staining, and flow cytometer propidium iodide stain-ing were performed to detect the effects of LCP on apoptosis and cell cycle arrest in HepG2 cells. Mi-tochondrial membrane potential (MMP) was observed through 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethyl-imidacarbocyanine assay. RESULTS & DISCUSSION: The Mw of the prepared LCP was 7.6 kDa, which was significantly lower than that of CP (140 kDa). Cell viability decreased with the increase in the concentration of LCP. The half-inhibitory concentration of 1.46 ± 0.02 mg/mL was determined. Treatment with 1.6 mg/mL LCP in-duced the apoptosis of HepG2 cells with the inhibition rate of 83.10% ± 4.72%, and the cell cycle was arrested in the S phase. Furthermore, the MMP of HepG2 cells decreased with the increase in LCP concentration. CONCLUSION: The enzymatically prepared LCP could inhibit the proliferation of HepG2 cells. This study provided a partial experimental basis and reference for LCP to become a potential functional food for anti-liver cancer.

The effect of interface angle on the thermal conductivity of Si/Ge superlattices.

Si/Ge superlattices (SLs) are good candidates for thermoelectric materials because of their remarkable thermal insulating performance compared with their bulk counterparts. In this paper, the non-equilibrium molecular dynamics (NEMD) simulation method was applied to investigate the thermal conductivity of Si/Ge SLs containing tilted interfaces. It was found that the thermal conductivity will be 4-5 times higher than that of other angles when the period length is 4-8 atomic layers and the interface angle is 45°. This phenomenon can be attributed to the smooth arrangement of the 45° interface which induces phonon coherent transport. Meanwhile, the thermal conductivity has not been improved due to the phonon localization although the phonons satisfy the coherent transport when the interface angle is 90°. Interestingly, the thermal conductivity is almost unchanged with the increasing interface angle when the period length is large enough which exceeds 20 atomic layers. The main reason for the unchanged thermal conductivity is due to the period length which is greater than the phonon coherence length inducing the phonon incoherent transport.

Correlation Analysis for Selection of Microtitanium Plates with Different Specifications for Use in a Cervical Vertebral Dome Expansion Laminoplasty.

OBJECTIVE: To analyze correlations between the selection of microtitanium plates with different specifications for use in a cervical vertebral dome expansion laminoplasty. METHODS: Sixteen patients that underwent the cervical vertebral dome expansion laminoplasty with a cervical spinal stenosis angioplasty procedure for treatment of their cervical spinal cords were recruited at our hospital. From February 2017 to September 2018, medical records confirmed that all patients underwent cervical CT and MRI tests pre- and postsurgery. The anteroposterior diameter of the spinal canal, changes in the cross-sectional area of the spinal canal, and the pre- and postsurgery distance of the cervical spinal cord after applying microtitanium plates with different lengths were measured by Mimics version 17.0 software (Materialise NV, Leuven, Belgium). A statistical regression and correlation analysis of relevant specification parameters of the microtitanium plate was then studied. RESULTS: As the size of the microtitanium plate increased, we found that the cross-sectional area of cervical spinal canal and distance between the descendants of the lamina and the distance of cervical spinal cord concordantly increased, and these data changes linearly. The regression equation associated with sagittal diameter, cross-sectional area, and posterior movement distance of the cervical spinal cord was obtained. CONCLUSION: According to the correlation analysis of imaging data changes, the regression equation was obtained to guide the selection of microtitanium plates with appropriate specifications in a cervical vertebral dome expansion laminoplasty.

Mid- and Long-Term Follow-Up Efficacy Analysis of 3D-Printed Interbody Fusion Cages for Anterior Cervical Discectomy and Fusion.

OBJECTIVE: To evaluate the safety and stability of 3D-printed interbody fusion cages (3D-printed cages) in anterior cervical discectomy and fusion (ACDF) by investigating the mid- and long-term follow-up outcomes. METHODS: In this prospective study, the clinical data of 30 patients with CSM admitted to the Second Hospital of Shanxi Medical University from May 2012 to May 2014 were analyzed. The cohort comprised 18 males and 12 females with an average age of 60.22 ± 3.2 years. All patients were examined by X-ray, CT and MRI before the operation. A total of 30 cases of CSM were treated by ACDF with 3D printed cage implantation. Mid- and long-term follow-ups were performed after the surgery. Clinical efficacy was evaluated by comparing the JOA score, SF-36 score, change in neurological function, cervical curvature index (CCI), vertebral intervertebral height (VIH) and fusion rate before the operation, 6 months after the operation, and at the last follow-up. RESULTS: Two of the 30 patients were lost to follow-up. The remaining patients were followed up for 48-76 (65.23 ± 3.54) months. The patients recovered satisfactorily with a significant clinical effect. The JOA score increased meanfully and the improvement rate was 89.4% at the final follow-up. The SF-36 score increased significantly from pre- to postoperatively. The height of the intervertebral space at the last follow-up was not statistically significantly different from that at 6 months after surgery (P > 0.05), showing that the height of the intervertebral space did not change much and the severity of cage subsidence (CS) decreased. The CCI improved from pre- to postoperatively. The CCI did not change much from the 6-month follow-up to the last follow-up. and the cage rate (CR) was 100% at the 6-month and last follow-ups. No severe complications, such as spinal cord injury, esophageal fistula, cerebrospinal fluid leakage, cervical hematoma or wound infection, occurred in any of the patients. CONCLUSION: The clinical and radiological results show that the application of 3D-printed cages in ACDF can significantly relieve symptoms. Moreover, 3D-printed cages can restore the curvature of the cervical spine, effectively maintain the intervertebral height for a long time, and prevent complications related to postoperative subsidence.

Tetramethylpyrazine inhibits proliferation of colon cancer cells in vitro.

BACKGROUND: Colon cancer is one of the most common malignancies worldwide, and chemotherapy is a widely used strategy in colon cancer clinical therapy. However, chemotherapy resistance is a major cause of disease recurrence and progression in colon cancer, and thus novel drugs for treatment are urgently needed. Tetramethylpyrazine (TMP), a component of the traditional Chinese medicine Chuanxiong Hort, has been proven to exhibit a beneficial effect in tumors. AIM: To investigate the potential anticancer activity of TMP in colon cancer and its underlying mechanisms. METHODS: Colon cancer cells were incubated with different concentrations of TMP. Cell viability was evaluated by crystal violet staining assay and cell counting kit-8 assay, and cell apoptosis and cell cycle were assessed by flow cytometry. RESULTS: TMP significantly inhibited the proliferation of colon cancer cells in a dose- and time-dependent manner. In addition, flow cytometry revealed that TMP induced cell cycle arrest at the G0/G1 phase. TMP treatment caused early stage apoptosis in SW480 cells, whereas it caused late stage apoptosis in HCT116 cells. CONCLUSION: Our studies demonstrated that TMP inhibits the proliferation of colon cancer cells in a dose- and time-dependent manner by inducing apoptosis and arresting the cell cycle at the G0/G1 phase. Our findings suggest that TMP might serve as a potential novel therapeutic drug in the treatment of human colon cancer.

Comparison of Imaging Parameters between a New Cervical Full Lamina Back Shift Spinal Canal Enlargement Technique and Single Open-Door Laminoplasty for Multisegment Cervical Spondylotic Myelopathy.

PURPOSE: To provide imaging evidence of the feasibility and clinical efficacy of a new full lamina back shift spinal canal enlargement technique. METHODS: A retrospective analysis was conducted on 64 patients with multisegment cervical spondylotic myelopathy caused by cervical stenosis. Of these, 32 patients underwent the new full lamina back shift spinal canal enlargement technique (as observation group) and 32 patients underwent single open-door miniature titanium plate internal fixation (as control group). The computed tomography (CT) data of both groups were imported into Mimics 17.0 software to measure the median sagittal diameter and cross-sectional area of the spinal canal. Photoshop CS5 was employed to measure the drift distance of the spinal cord on MR images to perform a comparative study of the imaging parameters from the two groups. RESULTS: The T2-weighted MR images in both groups showed continuous recovery of the cerebrospinal fluid signal in the C3 -C7 range. The enlarged spinal canal cross-sectional area (mm2 ) of each segment after the new full lamina back shift spinal canal enlargement technique was 130.90 ± 20.52 (C3 ), 180.81 ± 18.86 (C4 ), 240.48 ± 35.43 (C5 ), 145.93 ± 36.94 (C6 ), and 153.16 ± 36.28 (C7 ), and the enlarged median sagittal diameter (mm) was 5.31 ± 1.13 (C3 ), 8.8 ± 1.28 (C4 ), 10.28 ± 1.68 (C5 ), 9.46 ± 1.48 (C6 ), and 9.22 ± 1.12 (C7 ). Both parameters were significantly superior to single open-door miniature titanium plate internal fixation (P < 0.05). No significant difference was detected in the drift distance of the spinal cord between the two groups (P > 0.05). CONCLUSION: The new full lamina back shift spinal canal enlargement technique achieved a thorough spinal canal decompression effect on imaging while ensuring a reasonable spinal drift distance and few surgical complications. The clinical curative effect of the new technique was precise.

Deficiency of Microglial Autophagy Increases the Density of Oligodendrocytes and Susceptibility to Severe Forms of Seizures.

Excessive activation of mTOR in microglia impairs CNS homeostasis and causes severe epilepsy. Autophagy constitutes an important part of mTOR signaling. The contribution of microglial autophagy to CNS homeostasis and epilepsy remains to be determined. Here, we report that ATG7KO mice deficient for autophagy in microglia display a marked increase of myelination markers, a higher density of mature oligodendrocytes (ODCs), and altered lengths of the nodes of Ranvier. Moreover, we found that deficiency of microglial autophagy (ATG7KO) leads to increased seizure susceptibility in three seizure models (pilocarpine, kainic acid, and amygdala kindling). We demonstrated that ATG7KO mice develop severe generalized seizures and display nearly 100% mortality to convulsions induced by pilocarpine and kainic acid. In the amygdala kindling model, we observed significant facilitation of contralateral propagation of seizures, a process underlying the development of generalized seizures. Taken together, our results reveal impaired microglial autophagy as a novel mechanism underlying altered homeostasis of ODCs and increased susceptibility to severe and fatal generalized seizures.