Gfi1 controls the formation of effector CD8 T cells during chronic infection and cancer.

During chronic infections and tumor progression, CD8 T cells gradually lose their effector functions and become exhausted. These exhausted CD8 T cells are heterogeneous and comprised of different subsets, including self-renewing progenitors that give rise to Ly108 - CX3CR1 + effector-like cells. Generation of these effector-like cells is essential for the control of chronic infections and tumors, albeit limited. However, the precise cues and mechanisms directing the formation and maintenance of exhausted effector-like are incompletely understood. Using genetic mouse models challenged with LCMV Clone 13 or syngeneic tumors, we show that the expression of a transcriptional repressor, growth factor independent 1 (Gfi1) is dynamically regulated in exhausted CD8 T cells, which in turn regulates the formation of exhausted effector-like cells. Gfi1 deletion in T cells dysregulates the chromatin accessibility and transcriptomic programs associated with the differentiation of LCMV Clone 13-specific CD8 T cell exhaustion, preventing the formation of effector-like and terminally exhausted cells while maintaining progenitors and a newly identified Ly108 + CX3CR1 + state. These Ly108 + CX3CR1 + cells have a distinct chromatin profile and may represent an alternative target for therapeutic interventions to combat chronic infections and cancer. In sum, we show that Gfi1 is a critical regulator of the formation of exhausted effector-like cells.

HIF1α-glycolysis engages activation-induced cell death to drive IFN-γ induction in hypoxic T cells.

The role of HIF1α-glycolysis in regulating IFN-γ induction in hypoxic T cells is unknown. Given that hypoxia is a common feature in a wide array of pathophysiological contexts such as tumor and that IFN-γ is instrumental for protective immunity, it is of great significance to gain a clear idea on this. Combining pharmacological and genetic gain-of-function and loss-of-function approaches, we find that HIF1α-glycolysis controls IFN-γ induction in both human and mouse T cells activated under hypoxia. Specific deletion of HIF1α in T cells (HIF1α-/-) and glycolytic inhibition significantly abrogate IFN-γ induction. Conversely, HIF1α stabilization in T cells by hypoxia and VHL deletion (VHL-/-) promotes IFN-γ production. Mechanistically, reduced IFN-γ production in hypoxic HIF1α-/- T cells is due to attenuated activation-induced cell death but not proliferative defect. We further show that depletion of intracellular acetyl-CoA is a key metabolic underlying mechanism. Hypoxic HIF1α-/- T cells are less able to kill tumor cells, and HIF1α-/- tumor-bearing mice are not responsive to immune checkpoint blockade (ICB) therapy, indicating loss of HIF1α in T cells is a major mechanism of therapeutic resistance to ICBs. Importantly, acetate supplementation restores IFN-γ production in hypoxic HIF1α-/- T cells and re-sensitizes HIF1α-/- tumor-bearing mice to ICBs, providing an effective strategy to overcome ICB resistance. Taken together, our results highlight T cell HIF1α-anaerobic glycolysis as a principal mediator of IFN-γ induction and anti-tumor immunity. Considering that acetate supplementation (i.e., glycerol triacetate (GTA)) is approved to treat infants with Canavan disease, we envision a rapid translation of our findings, justifying further testing of GTA as a repurposed medicine for ICB resistance, a pressing unmet medical need.

Learning curve of junior surgeons in robot-assisted pedicle screw placement: a comparative cohort study.

OBJECTIVE: Robot-assisted technology has been gradually applied to pedicle screw placement in spinal surgery. This study was designed to detailedly evaluate the learning curve of junior surgeons in robot-assisted spine surgery. METHODS: From December 2020 to February 2022, 199 patients requiring surgical treatment with posterior pedicle screw fixation were prospectively recruited into the study. The patients were randomized to the robot-assisted group (the RA group) or the conventional freehand group (the CF group). Under the senior specialist's supervision, pedicle screws were placed by two junior fellows without prior experience. Cumulative summation (CUSUM) analysis was performed on the learning curve of pedicle screw placement for performing quantitative assessment based on the time of screw insertion. RESULTS: In total, 769 and 788 pedicle screws were placed in the RA and CF groups. Compared with the CF group, the learning duration in the RA group was shorter in the upper thoracic region (57 vs. 70 screws), but longer in the lower thoracic (62 vs. 58 screws) and the lumbosacral region (56 vs. 48 screws). The slope of learning curve was lower in the RA group than in the CF group. The screw accuracy in the RA group was superior to that in the CF group, especially in upper thoracic region (89.4% vs. 76.7%, P < 0.001). This disparity of accuracy became wider in deformity cases. In the upper thoracic region, the mean placement time was 5.34 ± 1.96 min in the RA group and 5.52 ± 2.43 min in the CF groups, while in the lower thoracic and lumbosacral regions, the CF group's mean placement times were statistically shorter. Three screw-related neural complications occurred in the CF group. CONCLUSION: Robot-assisted technique has its advantages in the upper thoracic region and deformity cases, which is easier and safer to insert pedicle screws. The robot-assisted technique allowed a short learning curve for junior surgeons and exhibited consistently excellent results even in the early application period.

PSD95 as a New Potential Therapeutic Target of Osteoarthritis: A Study of the Identification of Hub Genes through Self-Contrast Model.

Osteoarthritis (OA) is a worldwide joint disease. However, the precise mechanism causing OA remains unclear. Our primary aim was to identify vital biomarkers associated with the mechano-inflammatory aspect of OA, providing potential diagnostic and therapeutic targets for OA. Thirty OA patients who underwent total knee arthroplasty were recruited, and cartilage samples were obtained from both the lateral tibial plateau (LTP) and medial tibial plateau (MTP). GO and KEGG enrichment analyses were performed, and the protein-protein interaction (PPI) assessment was conducted for hub genes. The effect of PSD95 inhibition on cartilage degeneration was also conducted and analyzed. A total of 1247 upregulated and 244 downregulated DEGs were identified. Significant differences were observed between MTP and LTP in mechanical stress-related genes and activated sensory neurons based on a self-contrast model of human knee OA. Cluster analysis identified DLG4 as the hub gene. Cyclic loading stress increased PSD95 (encoded by DLG4) expression in LTP cartilage, and PSD95 inhibitors could alleviate OA progression. This study suggests that inhibiting PSD95 could be a potential therapeutic strategy for preventing articular cartilage degradation.

Suppression of microglial Ccl2 reduces neuropathic pain associated with chronic spinal compression.

Introduction: Chronic spinal compression is a common complication of spinal cord injury (SCI), which can lead to spinal stenosis or herniated discs. The ensuing neuropathic pain is often associated with the activation of microglia. In this investigation, our objective was to explore whether modifying the levels of chemokine (C-C motif) ligand 2 (Ccl2) in microglia could alleviate neuropathic pain resulting from chronic spinal compression. Methods: We used a public database to look for major altered gene associated in a SCI model established in rats. We then employed adeno-associated virus (AAV) vectors, expressing siRNA for the identified significantly altered gene under a microglia-specific TMEM119 promoter. We also tested the impact of this treatment in microglia in vivo on the severity of chronic spinal compression and associated pain using a ttw mouse model for progressive spinal compression. Results: We identified chemokine (C-C motif) ligand 2 (Ccl2) as the primary gene altered in microglia within a rat SCI model, utilizing a public database. Microglial Ccl2 levels were then found to be significantly elevated in disc specimens from SCI patients diagnosed with chronic spinal compression and strongly correlated with the Thompson classification of the degeneration level and pain score. Depletion of Ccl2 in microglia-specific TMEM119 promoter were developed to transfect mouse microglia in vitro, resulting in a proinflammatory to anti-inflammatory phenotypic adaption. In vivo depletion of Ccl2 in microglia mitigated the severity of chronic spinal compression and related pain in ttw mice, likely due to significant changes in pain-associated cytokines and factors. Conclusion: Disc microglia expressing high levels of Ccl2 may contribute to chronic spinal compression and SCI-associated pain. Therapeutically targeting Ccl2 in microglia could offer a potential avenue for treating chronic spinal compression and SCI-associated pain.

Percutaneous Curved Vertebroplasty Versus Unipedicular Approach Vertebroplasty for Acute Osteoporotic Vertebral Compression Fractures : A Randomized Controlled Trial.

STUDY DESIGN: Prospective randomized controlled trial. OBJECTIVE: To clarify whether percutaneous curved vertebroplasty (PCVP) is superior to conventional unipedicular approach vertebroplasty (UVP) in patients with acute osteoporotic vertebral compression fractures (OVCFs). SUMMARY OF BACKGROUND DATA: Unilateral curved vertebroplasty devices were designed and applied to provide better control of cement placement, which may be superior to traditional UVP for the treatment of acute OVCFs. MATERIALS AND METHODS: Patients with single-level OVCFs of <6 weeks duration and visual analog scale (VAS) of back pain 5 or more were randomly allocated to undergo PCVP or UVP and were followed up for 1 year. The primary outcome was overall VAS scores for back pain during 12 months of follow-up. The secondary outcomes were scores on the Oswestry disability index at each postprocedure clinic visit. Radiographic (cement distribution) and surgical data (operation time, fluoroscopy frequency, and cement volume) were assessed. Complications and adverse events were recorded. RESULTS: No statistical difference was found between the PCVP and UVP groups with respect to VAS and Oswestry disability index scores at any follow-up time point. Operative time, fluoroscopy frequency, and cement leakage were similar in both groups, while the PCVP techniques had a larger injection of polymethylmethacrylate (5.5 ± 1.4 vs . 4.2 ± 1.0 mL) and a greater dispersion pattern of cement ( P < 0.001). Post hoc observations found that the analgesic effect was positively correlated with the symmetry of bone cement distribution, but not with the surgical method. Two serious adverse events occurred in the vertebroplasty group: one stress ulcer and one allergic reaction. CONCLUSIONS: Although PCVP achieved more symmetrical cement distribution, which seemed to be associated with a greater analgesic effect, PCVP did not result in significantly greater pain relief than a UVP in the 12 months after treatment.

HiJAKing Immunotherapy-Resistant Melanoma for a Cure.

Immune checkpoint blockers (ICBs) have brought great promise to patients with advanced melanoma, a tumor type that was claimed largely incurable not long ago. However, therapeutic resistance to ICBs has limited their utility in the clinic. Here, we provide a commentary on recent research endeavors concerning ICB resistance in melanoma patients.

The CRL4DCAF6 E3 ligase ubiquitinates CtBP1/2 to induce apoptotic signalling and promote intervertebral disc degeneration.

Inflammation and apoptosis are two important pathological causes of intervertebral disc degeneration (IDD). The crosstalk between these two biological processes during IDD pathogenesis remains elusive. Herein, we discovered that chronic inflammation induced apoptosis through a cullin-RING E3 ligase (CRL)-dependent mechanism. Two cullin proteins, CUL4A and 4B, recruited DNA damage-binding protein 1 (DDB1), RING-box protein 1 (RBX1) and DDB1- and CUL4-associated factor 6 (DCAF6) to assemble a CRL4DCAF6 E3 ligase in intervertebral discs (IVDs) derived from IDD patients. The CRL4DCAF6 E3 ligase ubiquitinated and degraded C-terminal-binding protein 1 and 2 (CtBP1/2), two homologues of transcriptional corepressors. The degradation of CtBP1/2 disassociated from the p300-forkhead box O3a (FOXO3a) complex, inducing the expression of B-cell lymphoma 2 (Bcl2)-binding component 3 (BBC3) and causing BBC3-dependent apoptosis. TSC01131, a small molecule that specifically targets CUL4-DDB1 interaction, could inhibit the ubiquitination of CtBP1/2 in vitro and in vivo, thereby decreasing the BBC3 expression level and preventing apoptosis signalling. Using a mouse chronic inflammation model, we found that chronic inflammation could accelerate the IDD process through a conserved CRL4DCAF6-mediated mechanism. The administration of TSC01131 to mice could significantly improve the outcome of IDD. Collectively, our results revealed that inflammation-dependent CRL4DCAF6 E3 ligase triggered apoptosis through the removal of CtBP-mediated transrepression. The blockage of the CRL4DCAF6 E3 ligase by TSC01131 may represent a new therapeutic strategy for IDD treatment. KEY MESSAGES: CUL4A and CUL4B recruited DDB1, RBX1 and DCAF6 to assemble a CRL4DCAF6 E3 ligase in human IDD biopsies. The CRL4DCAF6 E3 ligase ubiquitinated and degraded CtBP1/2, causing BBC3-dependent apoptosis. A small molecule TSC01131 that specifically targets CUL4-DDB1 interaction could inhibit the ubiquitination of CtBP1/2, improving the outcome of IDD in a mouse model.

Is Complete Correction of Cervical Sagittal Malalignment Necessary During 4-Level Anterior Cervical Discectomy and Fusion Surgery in Patients With Kyphosis?

STUDY DESIGN: Retrospective analysis. OBJECTIVE: We investigated whether complete correction of cervical sagittal malalignment is necessary during 4-level anterior cervical discectomy and fusion (ACDF) in patients with kyphosis. METHODS: This retrospective study included 84 patients who underwent 4-level ACDF surgery at a university hospital between January 2010 and December 2015. Based on the degree of cervical lordosis correction, patients were categorized into the following groups: mild (0-10°), moderate (10-20°), and complete correction (>20°). The clinical outcomes, radiological parameters, and functional outcomes were analyzed. RESULTS: We observed no significant intergroup differences in the baseline characteristics. The cervical sagittal vertical axis (CSVA) correction loss at the final follow-up was lesser in the mild- and moderate- than in the complete-correction group. The spinocranial angle (SCA) and T1 slope (T1 S) were significantly higher in the moderate- and complete-correction groups than in the mild-correction group, 3 days postoperatively. The cervical proximal junctional kyphosis (CPJK), adjacent segment degeneration (ASD), and ASD following CPJK rates were higher in the complete-correction group. We observed no significant intergroup differences in postoperative complications; however, 5 patients showed internal fixation failure in the complete-correction group; 4 of these patients required reoperation. No significant intergroup difference was observed in the Japanese Orthopedic Association and neck disability index scores at any time point. CONCLUSIONS: A mild-to-moderate correction of cervical lordosis is superior to complete correction in patients with kyphosis who undergo 4-level ACDF because this approach is associated with lesser axial stress and CSVA correction loss.

Glucose-stimulated PGC-1α couples with CBP and Runx2 to mediate intervertebral disc degeneration through transactivation of ADAMTS4/5 in diet-induced obesity mice.

Emerging evidence suggests that type 2 diabetes mellitus (T2DM) is associated with the pathogenesis of intervertebral disc degeneration (IDD). However, it is still unclear how T2DM contributes to IDD. Herein, we observed the accumulation of blood glucose and degenerative lumbar discs in mice fed a high-fat diet. Detection of differentially expressed genes in degenerative lumbar discs revealed that ADAMTS4 (A Disintegrin and Metalloproteinase with Thrombospondin motifs) and ADAMTS5 genes were significantly increased. In vitro analyses demonstrated that Runt-Related Transcription Factor 2 (Runx2) recruited both PPARgamma Coactivator 1alpha (PGC-1α) and CREB-Binding Protein (CBP) to transactivate the expression of ADAMTS4/5. Glucose stimulation could dose-dependently induce the accumulation of PGC-1α and promoted the binding of the CBP-PGC-1α-Runx2 complex to the promoters of ADAMTS4/5. Depletion of CBP-PGC-1α-Runx2 complex members and treatment with either PGC-1α inhibitor SR-18292 or CBP inhibitor EML425 in vitro could dramatically inhibit the glucose-induced expression of ADAMTS4/5. Administration of SR-18292 and EML425 in diabetic mice could prevent the degeneration of lumbar discs. Collectively, our results revealed a molecular mechanism by which the hyperglycemia-dependent CBP-PGC-1α-Runx2 complex was required for the transactivation of ADAMTS4/5. The blockage of this complex in diabetic mice may help prevent IDD.

Minimally Invasive Full-endoscopic Posterior Cervical Foraminotomy and Discectomy: Introducing a Simple and Useful Localization Technique of the "V" Point.

OBJECTIVE: Conventional localization technique of V point for full-endoscopic posterior cervical foraminotomy and discectomy (FPCD) required repeated fluoroscopies, especially in patients with short and thick necks. To address this issue, the present study aimed to introduce a new localization technique of V point, and further evaluate its efficacy. METHODS: A K-wire was inserted and fixed at the pedicle eye under A/P fluoroscopy, then a working channel was established quickly along with it. Thirty-four patients who underwent minimally invasive FPCD assisted by the new technique were included in this study. The clinical and radiological data were collected and analyzed, including radiation dose, operative time, positioning time, visual analog scale (VAS) for neck and arm pain, neck disability index (NDI) scores, Cobb angle of operative level and range of motion of the cervical spine. RESULTS: All operations were performed successfully, and no iatrogenic nerve or vascular injury occurred. None of the patients needed to be transferred to open surgery or revision surgery. The mean radiation dose was found to be1.68 ± 0.36 mSv. The mean positioning time observed was 10.68 ± 5.42 min and the average operation time was 81.18 ± 10.87 min. The operation time significantly declined as the number of patients increased. A significant difference in operation time between the first (96.22 ± 10.36 min) and last quartile (75.00 ± 3.84 min) of cases was observed (t = 4.82, P < 0.001). The VAS scores for neck and arm pain, and NDI scores were significantly improved after surgery (PVAS-Neck <0.0001, PVAS-Arm <0.0001, PNDI <0.0001). Based on MacNab criteria, the excellent plus good rate was 91.17%. The Cobb angle of operative level and range of motion of the cervical spine were significantly improved postoperatively (t = 2.846, POA  = 0.015; t = 2.232, PROM-CA  = 0.026). CONCLUSION: The new image-assisted V point localization technique is simple and useful with little radiation exposure and short positioning time. FPCD assisted by the new technique could be a safe and effective alternative on properly selected patients.

Selective suppression of melanoma lacking IFN-γ pathway by JAK inhibition depends on T cells and host TNF signaling.

Therapeutic resistance to immune checkpoint blockers (ICBs) in melanoma patients is a pressing issue, of which tumor loss of IFN-γ signaling genes is a major underlying mechanism. However, strategies of overcoming this resistance mechanism have been largely elusive. Moreover, given the indispensable role of tumor-infiltrating T cells (TILs) in ICBs, little is known about how tumor-intrinsic loss of IFN-γ signaling (IFNγR1KO) impacts TILs. Here, we report that IFNγR1KO melanomas have reduced infiltration and function of TILs. IFNγR1KO melanomas harbor a network of constitutively active protein tyrosine kinases centered on activated JAK1/2. Mechanistically, JAK1/2 activation is mediated by augmented mTOR. Importantly, JAK1/2 inhibition with Ruxolitinib selectively suppresses the growth of IFNγR1KO but not scrambled control melanomas, depending on T cells and host TNF. Together, our results reveal an important role of tumor-intrinsic IFN-γ signaling in shaping TILs and manifest a targeted therapy to bypass ICB resistance of melanomas defective of IFN-γ signaling.

Roles of the Neuron-Restrictive Silencer Factor in the Pathophysiological Process of the Central Nervous System.

The neuron-restrictive silencer factor (NRSF), also known as repressor element 1 (RE-1) silencing transcription factor (REST) or X2 box repressor (XBR), is a zinc finger transcription factor that is widely expressed in neuronal and non-neuronal cells. It is a master regulator of the nervous system, and the function of NRSF is the basis of neuronal differentiation, diversity, plasticity, and survival. NRSF can bind to the neuron-restrictive silencer element (NRSE), recruit some co-repressors, and then inhibit transcription of NRSE downstream genes through epigenetic mechanisms. In neurogenesis, NRSF functions not only as a transcriptional silencer that can mediate the transcriptional inhibition of neuron-specific genes in non-neuronal cells and thus give neuron cells specificity, but also as a transcriptional activator to induce neuronal differentiation. Many studies have confirmed the association between NRSF and brain disorders, such as brain injury and neurodegenerative diseases. Overexpression, underexpression, or mutation may lead to neurological disorders. In tumorigenesis, NRSF functions as an oncogene in neuronal tumors, such as neuroblastomas, medulloblastomas, and pheochromocytomas, stimulating their proliferation, which results in poor prognosis. Additionally, NRSF-mediated selective targets gene repression plays an important role in the development and maintenance of neuropathic pain caused by nerve injury, cancer, and diabetes. At present, several compounds that target NRSF or its co-repressors, such as REST-VP16 and X5050, have been shown to be clinically effective against many brain diseases, such as seizures, implying that NRSF and its co-repressors may be potential and promising therapeutic targets for neural disorders. In the present review, we introduced the biological characteristics of NRSF; reviewed the progress to date in understanding the roles of NRSF in the pathophysiological processes of the nervous system, such as neurogenesis, brain disorders, neural tumorigenesis, and neuropathic pain; and suggested new therapeutic approaches to such brain diseases.

Comparison of Accuracy and Clinical Outcomes of Robot-Assisted Versus Fluoroscopy-Guided Pedicle Screw Placement in Posterior Cervical Surgery.

STUDY DESIGN: This was a prospective controlled study. OBJECTIVE: To compare the accuracy and clinical outcomes of robot-assisted (RA) and fluoroscopy-guided (FG) pedicle screw placement in posterior cervical surgery. METHODS: This study included 58 patients. The primary outcome measures were the 1-time success rate and the accuracy of pedicle screw placement according to the Gertzbein-Robbins scales. The secondary outcome measures, including the operative time, intraoperative blood loss, hospital stay, cumulative radiation time, radiation dose, intraoperative advent events, and postoperative complications, were recorded and analyzed. The Japanese Orthopedics Association (JOA) scores and Neck Disability Index (NDI) were used to assess the neurological function of patients before and at 3 and 6 months after surgery. RESULTS: The rate of grade A was significantly higher in the RA group than in the FG group (90.6% and 71.1%; P < .001). The clinically acceptable accuracy was 97.2% in the RA group and 90.7% in the FG group (P = .009). Moreover, the 1-time success rate was significantly higher in the RA group than in the FG group. The RA group had less radiation time (P < .001) and less radiation dose (P = .002) but longer operative time (P = .001). There were no significant differences in terms of intraoperative blood loss, hospital stay, intraoperative adverse events, postoperative complications, JOA scores, and NDI scores at each follow-up time point between the 2 groups. CONCLUSIONS: The RA technique achieved higher accuracy and 1-time success rate of pedicle screw placement in posterior cervical surgery while achieving comparable clinical outcomes.

Therapeutic Strategy of Percutaneous Transforaminal Endoscopic Decompression for Stenosis Associated With Adult Degenerative Scoliosis.

STUDY DESIGN: A retrospective study. OBJECTIVE: To investigate the effects of percutaneous transforaminal endoscopic decompression (PTED) for lumbar stenosis associated with adult degenerative scoliosis and to analyze the correlation between preoperative radiological parameters and postoperative surgical outcomes. METHODS: Two years of retrospective data was collected from 46 patients with lumbar stenosis associated with adult degenerative scoliosis who underwent PTED. The visual analog scale (VAS), Oswestry Disability Index, and modified MacNab criteria were used to evaluate the clinical outcomes. Multiple linear regression analysis was used to analyze the correlation between radiological parameters and surgical outcomes. RESULTS: The mean age of the 33 female and 13 male patients was 73.5 ± 8.1 years. The mean follow-up was 27.6 ± 3.5 months (range from 24 to 36). The average coronal Cobb angle was 24.5 ± 8.2°. There were better outcomes of the VAS for leg pain and Oswestry Disability Index after surgery. Based on the MacNab criteria, excellent or good outcomes were noted in 84.78% of patients. Multiple linear regression analysis showed that Cobb angle and lateral olisthy may be the predictors for low back pain. CONCLUSION: Transforaminal endoscopic surgery may be an effective and safe method for geriatric patients with lumbar stenosis associated with degenerative scoliosis. The predictive factors of clinical outcomes were severe Cobb angle and high degree lateral subluxation. Transforaminal endoscopic surgery may not be recommended for patients with Cobb angle larger than 30° combined with lateral subluxation.

Robot-assisted minimally invasive transforaminal lumbar interbody fusion versus open transforaminal lumbar interbody fusion: a retrospective matched-control analysis for clinical and quality-of-life outcomes.

Aim: To compare the screw accuracy and clinical outcomes between robot-assisted minimally invasive transforaminal lumbar interbody fusion (RA MIS-TLIF) and open TLIF in the treatment of one-level lumbar degenerative disease. Materials & methods: From May 2018 to December 2019, a consecutive series of patients undergoing robot-assisted minimally invasive one-level lumbar fusion procedures were retrospectively compared with matched controls who underwent one-level open TLIF procedures for clinical and quality-of-life outcomes. Results: A total of 52 patients underwent RA MIS-TLIF procedures (robot-assisted [RA] group) and 52 matched controls received freehand open TLIF procedures (open [OP] group). The RA group had more grade A screws with 96.2% one-time success rate of screw placement (p < 0.05). Besides, the RA group experienced less intraoperative blood loss and shorter length of hospital stay, while the OP group had shorter operative duration and cumulative radiation time (p < 0.001). What is more, the average VAS score for low back pain and ODI score in the RA group were lower than that in the OP group 1 month after operation (p < 0.05). Conclusion: The use of real-time, image-guided robot system may further expand the advantages of MIS-TLIF technique in terms of accuracy and safety.

Nuclear Pore Complex 62 Promotes Metastasis of Gastric Cancer by Regulating Wnt/ß-Catenin and TGF-ß Signaling Pathways.

Gastric cancer (GC) is the third leading cause of cancer-related deaths in the world. Tumor metastasis is considered one of the main factors for GC development. Nup62 is a member of the nuclear pore complex (NPC). It bridges the nuclear envelope, is important in nucleocytoplasmic exchange, and is associated with cancer. This study aimed to investigate the role of Nup62 in GC metastasis. The relationship between the expression level of Nup62 in GC and patient survival was evaluated using Kaplan-Meier analysis. Then Nup62 expression in GC tissues and matched normal gastric tissues was analyzed by immunohistochemistry and that in cell lines by Western blot analysis. Furthermore, clonogenic and Transwell migration assays were performed, and the expression of epithelial-mesenchymal transition (EMT) proteins was detected to determine the metastatic functional roles of Nup62 in GC. Compared with the adjacent normal tissues, Nup62 was found to be upregulated in GC tissues using software prediction and detecting clinical specimens and cell lines. Moreover, the downregulation of Nup62 suppressed colony formation and decreased the number of migrated cells. In contrast, Nup62 overexpression promoted colony formation and increased the number of migrated cells. Further functional studies showed that the abnormal expression of Nup62 influenced cell migration and EMT through wingless/ß-catenin (Wnt/ß-catenin) and transforming growth factor (TGF)-ß signaling pathways. In summary, the findings indicate that Nup62 regulates cell migration by interfering with Wnt/ß-catenin and TGF-ß signaling pathways in GC.

Clinical application of Myelopathy-hand Functional Evaluation System in evaluating the postoperative hand motor function for myelopathy patients.

OBJECTIVE: Recovery of hand motor function after surgical treatment in myelopathy patients is commonly observed. Accurate evaluation of postoperative hand function contributes to assessing the efficacy of surgical treatment. However, no objective and effective evaluation method has been widely accepted in clinical practice. Therefore, the study aimed to explore the value of Myelopathy-hand Functional Evaluation System (MFES) in assessing the postoperative hand function for myelopathy patients. MATERIAL AND METHOD: MFES mainly consist of a pair of wise-gloves and a computer with software. One hundred and thirty myelopathy patients were included and all of them received optimal surgery treatment. The Japanese Orthopaedic Association (JOA) scores were marked at preoperative and at 6 months after surgery. All patients were asked to perform the 10-s grip and release test, and the hand movements were simulated and converted into waveforms by MFES. The waveform parameters were measured and analyzed. RESULTS: The JOA scores and the number of grip-and-release (G-R) cycles significantly increased after surgery. Correspondingly, the waveforms of ulnar three fingers were significantly higher and narrower, along with the significantly declined average time per cycle in postoperative. The a/b ratio (Wave height/wave width) of five fingers were significantly higher in postoperative than that in preoperative. Based on the improvement rate of a/b, the excellent and good rate of surgical outcomes was 62.30 %, which was significantly higher than that (47.69 %) based on the improvement rate of JOA scores (P = 0.019). CONCLUSION: MFES is an effective assessment tool in evaluating the postoperative hand function for myelopathy patients.

MiR-874-3p plays a protective role in intervertebral disc degeneration by suppressing MMP2 and MMP3.

Intervertebral disc degeneration (IDD) is a spinal degenerative disease and one of the most important causes of musculoskeletal disability. Matrix metalloproteinase (MMP)-mediated extracellular matrix degradation is the core process of IDD. The regulators of MMPs in the intervertebral disc are still not fully known. In this study, using quantitative reverse transcription PCR, luciferase reporter assay, Western blotting, immunofluorescence, flow cytometry, and Cell Counting Kit-8 assay, we found that the miR-874-3p expression level was significantly decreased in IDD patients. MiR-874-3p could target and repress MMP2 and MMP3 expression in nucleus pulposus cells. These results could improve the understanding of IDD and provide a possible diagnostic marker and treatment candidate for IDD. The miR-874-3p/MMP2/MMP3 axis might also provide direction for future cancer and inflammation investigations.

Cervical Angina: A Literature Review on Its Diagnosis, Mechanism, and Management.

Cervical angina has been defined as chest pain that resembles true cardiac angina but originates from the disorders of the cervical spine. Thus, physicians and spine surgeons alike should raise awareness of this unusual condition for diagnosis and treatment. Particularly when neurologic signs and symptoms are present, there should be a strong suspicion for cervical angina in any patient with inadequately explained noncardiac chest pain. Cervical angina can be diagnosed according to negative cardiac workups, positive neurologic examination, and cervical radiographic findings (herniated disk, spinal cord compression, or foraminal encroachment). However, the mechanisms of pain production in cervical angina remain unclear. Previous studies attributed the pain to cervical nerve root compression, cervical sympathetic afferent fibers, referred pain, or lesions of the posterior horn of the spinal cord. Conservative treatments, which include neck collar fixation, head traction, and nonsteroidal anti-inflammatory drugs, have been determined to be successful in most patients with cervical angina. But when conservative treatment fails, anterior cervical surgery with complete decompression of the spinal cord and/or nerve root has been identified to effectively relieve cervical angina symptoms.