The inhibition of Aurora A kinase regulates phospholipid remodeling by upregulating LPCAT1 in glioblastoma.

Metabolic reprogramming is a common feature of glioblastoma (GBM) progression and metastasis. Altered lipid metabolism is one of the most prominent metabolic alterations in cancer. Understanding the links between phospholipid remodeling and GBM tumorigenesis may help develop new anticancer strategies and improve treatments to overcome drug resistance. We used metabolomic and transcriptomic analyses to systematically investigate metabolic and molecular changes in low-grade glioma (LGG) and GBM. We then re-established the reprogrammed metabolic flux and membrane lipid composition in GBM based on metabolomic and transcriptomic analyses. By inhibiting Aurora A kinase via RNA interference (RNAi) and inhibitor treatment, we investigated the effect of Aurora A kinase on phospholipid reprogramming LPCAT1 enzyme expression and GBM cell proliferation in vitro and in vivo. We found that GBM displayed aberrant glycerophospholipid and glycerolipid metabolism compared with LGG. Metabolic profiling indicated that fatty acid synthesis and uptake for phospholipid synthesis were significantly increased in GBM compared to LGG. The unsaturated phosphatidylcholine (PC) and phosphatidylethanolamine (PE) levels were significantly decreased in GBM compared to LGG. The expression level of LPCAT1, which is required for the synthesis of saturated PC and PE, was upregulated in GBM, and the expression of LPCAT4, which is required for the synthesis of unsaturated PC and PE, was downregulated in GBM. Notably, the inhibition of Aurora A kinase by shRNA knockdown and treatment with Aurora A kinase inhibitors such as Alisertib, AMG900, or AT9283 upregulated LPCAT1 mRNA and protein expression in vitro. In vivo, the inhibition of Aurora A kinase with Alisertib increased LPCAT1 protein expression. Phospholipid remodeling and a reduction in unsaturated membrane lipid components were found in GBM. Aurora A kinase inhibition increased LPCAT1 expression and suppressed GBM cell proliferation. The combination of Aurora kinase inhibition with LPCAT1 inhibition may exert promising synergistic effects on GBM.

Speech Recognition of Accented Mandarin Based on Improved Conformer.

The convolution module in Conformer is capable of providing translationally invariant convolution in time and space. This is often used in Mandarin recognition tasks to address the diversity of speech signals by treating the time-frequency maps of speech signals as images. However, convolutional networks are more effective in local feature modeling, while dialect recognition tasks require the extraction of a long sequence of contextual information features; therefore, the SE-Conformer-TCN is proposed in this paper. By embedding the squeeze-excitation block into the Conformer, the interdependence between the features of channels can be explicitly modeled to enhance the model's ability to select interrelated channels, thus increasing the weight of effective speech spectrogram features and decreasing the weight of ineffective or less effective feature maps. The multi-head self-attention and temporal convolutional network is built in parallel, in which the dilated causal convolutions module can cover the input time series by increasing the expansion factor and convolutional kernel to capture the location information implied between the sequences and enhance the model's access to location information. Experiments on four public datasets demonstrate that the proposed model has a higher performance for the recognition of Mandarin with an accent, and the sentence error rate is reduced by 2.1% compared to the Conformer, with only 4.9% character error rate.

An Experimental Study on the Optimal Timing for the Repair of Incomplete Facial Paralysis by Hypoglossal-facial 'Side'-to-side Neurorrhaphy in Rats.

OBJECTIVE: To investigate the optimal timing for the repair of persistent incomplete facial paralysis by hypoglossal-facial 'side'-to-side neurorrhaphy in rats. METHODS: A total of 30 adult rats with crushed and bulldog-clamped facial nerve injury were randomly divided into 5 groups (n = 6 each) that were subjected to injury without nerve repair or with immediate repair, 2-week-delayed repair, 4-week-delayed repair, or 8-week-delayed repair. Three months later, the effects of repair in each rat were evaluated by facial symmetry assessment, electrophysiological examination, retrograde labeling, and axon regeneration measurement. RESULTS: At 3 months after injury, the alpha angle significantly increased in the group of rats with 4-week-delayed repair compared with the other four groups. Upon stimulation of the facial nerve or Pre degenerated nerve, the muscle action potentials MAPs were recorded in the whisker pad muscle, and the MAP amplitude and area under the curve in the 4-week-delayed repair group were significantly augmented at 3 months post-injury. Similarly, the number of retrograde-labeled motor neurons in the facial and hypoglossal nuclei was quantified to be significantly greater in the 4-week-delayed repair group than in the other groups, and a large number of regenerated axons was also observed. CONCLUSION: The results of this study demonstrated that hemiHN-FN neurorrhaphy performed 4 weeks after facial nerve injury was most effective in terms of the functional recovery of axonal regeneration and activation of facial muscles.

Comparison of thoracolumbar versus non-thoracolumbar osteoporotic vertebral compression fractures in risk factors, vertebral compression degree and pre-hospital back pain.

BACKGROUND: Thoracolumbar spine is at high risk of osteoporotic vertebral compression fractures (OVCF). This study aimed to identify the differences in risk factors, vertebral compression degree and back pain characteristics of thoracolumbar OVCF (TL-OVCF) and non-thoracolumbar OVCF (nTL-OVCF). METHODS: OVCF patients hospitalized in a spine center between June 2016 and October 2020 were retrospectively studied. Demographics, comorbidity, spine trauma, bone mineral density, duration of pre-hospital back pain, extent of vertebral marrow edema, and degree of vertebral compression of patients with nTL-OVCF were summarized and compared to those with TL-OVCF. RESULTS: A total of 944 patients with acute single-segment OVCF were included. There were 708 (75.0%) TL-OVCF located in T11-L2 and 236 (25.0%) nTL-OVCF in lower lumbar (L3-L5) and middle thoracic (T5-T10) spine. The female-male ratio was 4.1 in nTL-OVCF and differed not significantly from TL-OVCF. The middle thoracic OVCF were older and had higher comorbidity of coronary heart disease (21.3%) and cerebral infarction (36.3%) than TL-OVCF (12.1% and 20.6%). In nTL-OVCF the ratio of apparent spine trauma (44.9%) and pre-hospital back pain ≤ 1 week (47.5%) was lower than in TL-OVCF (66.9% and 62.6%). The T-score value of lumbar spine was - 2.99 ± 1.11, - 3.24 ± 1.14, - 3.05 ± 1.40 in < 70, 70-80, > 80 years old TL-OVCF and differed not significantly from nTL-OVCF. The lower lumbar OVCF had more cranial type of vertebral marrow edema (21.8%) and fewer concurrent lumbodorsal fasciitis (30.8%) than TL-OVCF (16.8% and 43.4%). In TL-OVCF the anterior-posterior vertebral height ratio was lower with back pain for > 4 weeks than for ≤ 1, 1-2, and 2-4 weeks. In nTL-OVCF the degree of vertebral compression differed not significantly with pre-hospital back pain for ≤ 1, 1-2, 2-4, and > 4 weeks. CONCLUSIONS: Thoracolumbar spine has 2-folds higher risk of OVCF than non-thoracolumbar spine. Non-thoracolumbar OVCF are not associated with female gender, apparent spine trauma or poor bone mineral density, but tend to maintain the degree of vertebral compression and cause longer duration of pre-hospital back pain.

Comparison of acute single versus multiple osteoporotic vertebral compression fractures in radiographic characteristic and bone fragility.

BACKGROUND: Osteoporotic vertebral compression fractures (OVCF) are common in aged population with bone fragility. This study aimed to identify the radiographic and bone fragility characteristic of acute single and multiple OVCF. METHODS: OVCF patients hospitalized in a spine center between June 2016 and October 2020 were retrospectively studied. Demographics, comorbidity, bone mineral density, spine trauma, duration of pre-hospital back pain, anatomical location and distribution pattern of OVCF, extent of vertebral marrow edema, and degree of vertebral compression of patients with multi-segment vertebral fractures (MSVF) were summarized and compared to those with single segment vertebral fractures (SSVF). RESULTS: A total of 1182 patients with 1530 acute fractured vertebrae were included. There were 944 SSVF (79.9%) and 238 MSVF (20.1%) simultaneously involving two (MSVF-2) or three and more vertebra (MSVF-3/m). The Female-Male ratio was 4.4 and differed not significantly between SSVF and MSVF. Females in SSVF were younger than males while MSVF-2 tended to occur in older females. L1, T12, and L2 were the three most frequently fractured vertebra and MSVF involved more vertebra in thoracic and lumbar spine. 31.1% in MSVF-2 and 83.1% in MSVF-3/m had at least two vertebral fractures in adjacent. The fractured thoracolumbar vertebra in MSVF was less compressed than that in SSVF. Apparent spine trauma was reported by 61.4% of SSVF, 44.1% of MSVF-2, and 36.3% of MSVF-3/m, while early hospitalization with pre-hospital back pain ≤ 1 week was 58.9% in SSVF, 45.3% in MSVF-2, and 25.9% in MSVF-3/m. Only females aged 70-80 years old in MSVF-3/m showed lower baseline bone mineral density than in MSVF-2 and SSVF. MSVF were not associated with increased comorbidity of hypertension, diabetes, coronary heart disease, cerebral infarction, and chronic pulmonary disease. CONCLUSIONS: 20% of acute OVCF can involve multiple vertebra without significant spine trauma or lower baseline bone mineral density. Multiple OVCF tend to occur in adjacent vertebra with less thoracolumbar vertebral compression but longer duration of pre-hospital back pain.

[Preliminary experiences in minimally invasive transforaminal lumbar interbody fusion].

OBJECTIVE: To explore clinical application of minimally invasive transforaminal lumbar interbody fusion (TLIF) for the management of lumbar disorders and discuss its indications, surgical techniques and clinical effectiveness. METHODS: From Jan 2005 to Dec 2006, 31 selected patients (22 males and 9 females, aged from 41 to 63 years) with degenerative lumbar diseases were treated with minimally invasive TLIF assisted by METRx X-Tube micro-endoscopy system. The index diagnosis was lumbar disc herniation with Lumbar spinal stenosis in 7, lumbar disc herniation with segmental instability in 16, grade 1 to 2 of lumbar spondylolisthesis in 8. The surgical methods was performed with bilateral or unilateral pedicle screws insertion and a single rectangle cage posterolateral placement. The operating time, blood loss, blood transfusion, drainage, visual analogue scale (VAS), preoperative and postoperative JOA scores were observed as well as radiographic evaluation. The results were compared with standard TLIF group respectively. RESULTS: A total of 116 pedicle screws and 31 cages were implanted of which 4 patients were treated with unilateral pedicle screws fixation. Four pedicle screws were found misplaced in CT scans after surgery. The average operating time was 199 min, blood loss 359 ml, volume of transfusion 32 ml drainage 81 ml, and VAS was 2.37 about 72 hours after surgery, which had statistic difference compared with control group. There was no statistic difference on postoperative improvement rate and JOA scores in two groups. CONCLUSIONS: Minimally invasive TLIF minimizes paraspinal muscle trauma and blood loss, shortens the operating and recovery time. A good long-term outcome can be gained compared with standard procedures.

Action of Schwann cells implanted in cerebral hemorrhage lesion.

OBJECTIVE: To investigate whether there is neogenesis of myelin sheath and neuron after transplantation of Schwann cells into cerebral hemorrhage lesion. METHODS: Schwann cells were expanded, labeled with BrdU in vitro and transplanted into rat cerebral hemorrhage with blood extracted from femoral artery and then injected into the basal nuclei. Double immunohistochemistry staining and electron microscopy were used to detect the expression of BrdU/MBP and BrdU/GAP-43 and remyelination. RESULTS: BrdU/MBP double positive cells could be seen at 1 week up to 16 weeks after transplantation of Schwann cells. Thin remyelination was observed under electron microscope. GAP-43 positive cells appeared after 12 weeks and were found more in Hippocamp. CONCLUSIONS: Grafted Schwann cells participate in remyelination and promoter nerve restore in rat cerebral hemorrhage.

Induction of functional recovery by co-transplantation of neural stem cells and Schwann cells in a rat spinal cord contusion injury model.

OBJECTIVE: To study the transplantation efficacy of neural stem cells (NSCs) and Schwann cells (SC) in a rat model of spinal cord contusion injury. METHODS: Multipotent neural stem cells (NSCs) and Schwann cells were harvested from the spinal cords of embryonic rats at 16 days post coitus and sciatic nerves of newborn rats, respectively. The differential characteristics of NSCs in vitro induced by either serum-based culture or co-culture with SC were analyzed by immunofluorescence. NSCs and SCs were co-transplanted into adult rats having undergone spinal cord contusion at T9 level. The animals were weekly monitored using the Basso-Beattie-Bresnahan locomotor rating system to evaluate functional recovery from contusion-induced spinal cord injury. Migration and differentiation of transplanted NSCs were studied in tissue sections using immunohistochemical staining. RESULTS: Embryonic spinal cord-derived NSCs differentiated into a large number of oligodendrocytes in serum-based culture upon the withdrawal of mitogens. In cocultures with SCs, NSCs differentiated into neuron more readily. Rats with spinal cord contusion injury which had undergone transplantation of NSCs and SCs into the intraspinal cavity demonstrated a moderate improvement in motor functions. CONCLUSIONS: SC may contribute to neuronal differentiation of NSCs in vitro and in vivo. Transplantation of NSCs and SCs into the affected area may be a feasible approach to promoting motor recovery in patients after spinal cord injury.

Biomechanical evaluation of vertebroplasty using calcium sulfate cement for thoracolumbar burst fractures.

OBJECTIVE: To evaluate the biomechanical performance of vertebroplasty using calcium sulfate cement for thoracolumbar burst fractures. METHODS: Sixteen bovine thoracolumbar spines (T11-L1) were divided into 4 groups (A,B,C and D). After burst-fracture model was created, 12 vertebral bodies in Groups A, B and C were augmented with calcium sulfate cement (CSC), calcium phosphate cement (CPC) and polymethylmethacrylate (PMMA) bone cement, respectively. Each anterior vertebral body height was measured with a caliper at 4 time points: intact conditions (HInt), post-fracture (HFr), post-reduction (HRe) and post-vertebroplasty (HVP). The filling volume of 3 different bone cements was also measured. Each vertebral body was compressed at 0.5 mm/s using a hinged plating system on a materials testing machine to 50% of the post-vertebroplasty height to determine strength and stiffness. Difference was checked using t test or One-way ANOVA. RESULTS: The average strike energy was 66.2 J. Vertebroplasty with different cements could sustain vertebral height. The average filling volume of bone cement in 3 groups was 4.35 ml (CSC), 3.72 ml (CPC) and 3.95 ml (PMMA), respectively, and there was no statistically significant difference among them (P larger than 0.05). Vertebroplasty with PMMA completely restored strength (116%) and stiffness (105%). CSC or CPC partly recovered vertebral strength and stiffness. However, greater strength restoration was got with CSC (1659 N) as compared with CPC (1011N, P less than 0.01). Regarding stiffness, differences between CSC (140 N/mm+/-40 N/mm)and the other two bone cements (CPC:148 N/mm+/-33 N/mm, PMMA:236 N/mm+/-97 N/mm) were not significant (P larger than 0.05). CONCLUSIONS: For a burst-fracture of calf spine, use of CSC for vertebroplasty yields similar vertebral stiffness as compared with PMMA or CPC. Although augmentation with CSC partly obtains the normal strength, this treatment still can be applied in thoracolumbar burst fractures with other instrumental devices in light of its bioactivation.

Protective effect of isoflurane and sevoflurane on ischemic neurons and expression of Bcl-2 and ICE genes in rat brain.

OBJECTIVE: To study the protective effect of volatile anesthetics, isoflurane and sevoflurane, on ischemic neurons after cerebral ischemia-reperfusion in rats and its possible molecular mechanism. METHODS: Rat cerebral ischemia-reperfusion model was developed by occlusion of the middle cerebral artery (MCA) and bilateral common carotid arteries (CCAs) 1 h after reperfusion. Using flow cytometry (FCM) and Northern blot hybridization, we calculated the number of apoptotic bodies and detected the expression of bcl-2 mRNA and interleukin-1beta converting enzyme (ICE) mRNA. RESULTS: The apoptotic bodies in hippocampus analyzed by FCM peaked at appeared 24 h after reperfusion, and decreased about 54% and 40%, respectively, after treatment with isoflurane and sevoflurane, as compared with ischemic group. There was no significant difference in the expression of bcl-2 mRNA and ICE mRNA between the inhaled anesthetic groups and ischemic group in hippocampus 24 h after MCA/CCAs occlusion. CONCLUSION: Isoflurane and sevoflurane partially inhibit apoptosis but have no significant effect on the expression of bcl-2 and ICE genes.

Outcomes of Microendoscopic Discectomy and Percutaneous Transforaminal Endoscopic Discectomy for the Treatment of Lumbar Disc Herniation: A Comparative Retrospective Study.

STUDY DESIGN: Retrospective, case control evaluation of 86 patients who underwent microendoscopic discectomy (MED) and percutaneous transforaminal endoscopic discectomy (PTED) for the treatment of lumbar disc herniation (LDH). PURPOSE: To evaluate the safety and the outcomes of MED and PTED for the treatment of LDH. OVERVIEW OF LITERATURE: MED and PTED are minimally invasive surgical techniques for lower back pain. Studies to date have shown that MED and PTED are safe and effective treatment modalities for LDH. METHODS: A retrospective study was performed in patients with LDH treated with MED (n=50) and transforaminal endoscopic discectomy (PTED; n=36) in our hospital. All patients were followed-up with self-evaluation questionnaires, Oswestry disability index (ODI), medical outcomes study 36-item short form health survey and MacNab criteria. All the patients in both groups were followed up to 12 months after the operation. RESULTS: ODI questionnaire responses were not statistically different between the MED and PTED groups (53.00 vs. 48.72) before treatment. Average scores and minimal disability after 5 days to 12 months of follow-up were 4.96 in the MED group and 3.61 in the PTED group. According to MacNab criteria, 92.0% of the MED group and 94.4% of the PTED group had excellent or good results with no significant difference. CONCLUSIONS: There was no significant difference between MED and PTED outcomes. Further large-scale, randomized studies with long-term follow-up are needed.