Oxidative stress-induced EGR1 upregulation promotes NR4A3-mediated nucleus pulposus cells apoptosis in intervertebral disc degeneration.

This study aimed to reveal the specific role of early growth response protein 1 (EGR1) and nuclear receptor 4A3 (NR4A3) in nucleus pulposus cells (NPCs) and the related molecular mechanism and to identify a new strategy for treating intervertebral disc degeneration (IVDD). Bioinformatics analysis was used to explore and predict IVDD-related differentially expressed genes, and chromatin immunoprecipitation sequencing (ChIP-seq) revealed NR4A3 as the EGR1 target gene. An in vitro NPC model induced by tributyl hydrogen peroxide (TBHP) and a rat model induced by fibrous ring acupuncture were established. Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemical staining, immunofluorescence staining, and flow cytometry were used to detect the effects of EGR1 and NR4A3 knockdown and overexpression on NPC apoptosis and the expression of extracellular matrix (ECM) anabolism-related proteins. Interactions between EGR1 and NR4A3 were analyzed via ChIP-qPCR and dual luciferase assays. EGR1 and NR4A3 expression levels were significantly higher in severely degenerated discs (SDD) than in mildly degenerated discs (MDD), indicating that these genes are important risk factors in IVDD progression. ChIP-seq and RNA-seq revealed NR4A3 as a direct downstream target of EGR1, and this finding was verified by ChIP-qPCR and dual luciferase reporter experiments. Remarkably, the rescue experiments showed that EGR1 promotes TBHP-induced NPC apoptosis and impairs ECM anabolism, dependent on elevated NR4A3 expression. In summary, the EGR1-NR4A3 axis mediates the progression of NPC apoptosis and ECM impairment and is a potential therapeutic target in IVDD.

CircCOX6A1 suppresses osteogenic differentiation and aggravates osteoporosis via miR-512-3p/DYRK2 axis.

BACKGROUND: Osteoporosis (OP), characterized by compromised bone integrity and increased fracture risk, poses a significant health challenge. Circular RNAs (circRNAs) have emerged as crucial regulators in various pathophysiological processes, prompting investigation into their role in osteoporosis. This study aimed to elucidate the involvement of circCOX6A1 in OP progression and understand its underlying molecular mechanisms. The primary objective was to explore the impact of circCOX6A1 on bone marrow-derived mesenchymal stem cells (BMSCs) and its potential interactions with miR-512-3p and DYRK2. METHODS: GSE161361 microarray analysis was employed to assess circCOX6A1 expression in OP patients. We utilized in vitro and in vivo models, including BMSC cultures, osteogenic differentiation assays, and an OVX-induced mouse model of OP. Molecular techniques such as quantitative RT-PCR, western blotting, and functional assays like alizarin red staining (ARS) were employed to evaluate circCOX6A1 effects on BMSC proliferation, apoptosis, and osteogenic differentiation. The interaction between circCOX6A1, miR-512-3p, and DYRK2 was investigated through dual luciferase reporter assays, RNA immunoprecipitation, and RNA pull-down assays. RESULTS: CircCOX6A1 was found to be upregulated in osteoporosis patients, and its expression inversely correlated with osteogenic differentiation of BMSCs. CircCOX6A1 knockdown enhanced osteogenic differentiation, as evidenced by increased mineralized nodule formation and upregulation of osteogenic markers. In vivo, circCOX6A1 knockdown ameliorated osteoporosis progression in OVX mice. Mechanistically, circCOX6A1 acted as a sponge for miR-512-3p, subsequently regulating DYRK2 expression. CONCLUSION: This study provides compelling evidence for the role of circCOX6A1 in osteoporosis pathogenesis. CircCOX6A1 negatively regulates BMSC osteogenic differentiation through the miR-512-3p/DYRK2 axis, suggesting its potential as a therapeutic target for mitigating OP progression.

Bioinformatics analysis and validation of mesenchymal stem cells related gene MT1G in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is a primary malignant bone tumor arising from mesenchymal cells. The standard clinical treatment for OS involves extensive tumor resection combined with neoadjuvant chemotherapy or radiotherapy. OS's invasiveness, lung metastasis, and drug resistance contribute to a low cure rate and poor prognosis with this treatment. Metallothionein 1G (MT1G), observed in various cancers, may serve as a potential therapeutic target for OS. METHODS: OS samples in GSE33382 and TARGET datasets were selected as the test cohorts. As the external validation cohort, 13 OS tissues and 13 adjacent cancerous tissues from The Second Affiliated Hospital of Nanchang University were collected. Patients with OS were divided into high and low MT1G mRNA-expression groups; differentially expressed genes (DEGs) were identified as MT1G-related genes. The biological function of MT1G was annotated using Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO) and gene set enrichment analysis (GSEA). Gene expression correlation analysis and competing endogenous RNA (ceRNA) regulatory network construction were used to determine potential biological regulatory relationships of DEGs. Survival analysis assessed the prognostic value of MT1G. RESULTS: MT1G expression increased in OS samples and presented higher in metastatic OS compared with non-metastatic OS. Functional analyses indicated that MT1G was mainly associated with spliceosome. A ceRNA network with DEGs was constructed. MT1G is an effective biomarker predicting survival and correlated with increased recurrence rates and poorer survival. CONCLUSIONS: This research identified MT1G as a potential biomarker for OS prognosis, highlighting its potential as a therapy target.

Homocysteine modulates CXCL10/CXCR3 axis activity to induce endothelial dysfunction.

Elevated homocysteine (Hcy) levels have been linked to the development of cardiovascular diseases, notably endothelial dysfunction, a critical precursor to atherosclerosis. In this extensive investigation, we explore the intricate pathways through which Hcy influences endothelial dysfunction, with particular attention to the CXCL10/CXCR3 axis. Employing a dual approach encompassing both in vitro and in vivo models, we scrutinize the repercussions of Hcy exposure on endothelial functionality. Our results reveal that Hcy significantly impairs crucial endothelial processes, including cell migration, proliferation, and tube formation. Concomitantly, Hcy upregulates the expression of adhesion molecules, exacerbating endothelial dysfunction. In a murine hyperhomocysteinemia (HHcy) model, we observed a parallel increase in plasma Hcy levels and adverse vascular effects. Moreover, our study unraveled a pivotal role of the CXCL10/CXCR3 axis in Hcy-induced endothelial dysfunction. Hcy exposure led to the upregulation of CXCL10 and CXCR3, both in vitro and in HHcy mice. Importantly, the blockade of this axis, achieved through specific antibodies or NBI-74330, mitigated the detrimental effects of Hcy on endothelial function. In conclusion, our findings illuminated the central role of the CXCL10/CXCR3 axis in mediating Hcy-induced endothelial dysfunction, providing valuable insights for potential therapeutic strategies in managing HHcy-related cardiovascular diseases.

Modified Percutaneous Endoscopic Interlaminar Discectomy through the Near-spinous Process Approach for L4/5 Disc Herniation: A Retrospective Clinical Study.

OBJECTIVE: Compared with traditional open surgery, percutaneous endoscopic lumbar discectomy (PELD) has the advantages of less trauma, faster recovery, and less postoperative pain, so it has been widely used in the field of spinal surgery. However, it still has the defect of intraoperative fluoroscopy occurrences, complications, and even the risk of damage to the spinal cord and nerve. This study aims to compare the clinical efficacy of modified percutaneous endoscopic interlaminar discectomy (MPEID) with percutaneous endoscopic transforaminal discectomy (PETD) in treating L4/5 lumbar disc herniation (LDH) and to evaluate the effectiveness and safety of MPEID. METHODS: Thirty-four L4/5 LDH patients treated at the Second Affiliated Hospital of Nanchang University from June 2020 to June 2021 were studied retrospectively. Seventeen underwent MPEID and seventeen PETD. Variables analyzed included demographics, operative duration, intraoperative fluoroscopy occurrences, and surgical outcomes. Effectiveness was evaluated using the visual analogue scale (VAS), Oswestry disability index (ODI), and modified MacNab criteria. Lumbar Magnetic Resonance Imaging (MRI) was used to assess radiological outcomes. A paired t-test was performed to compare intragroup pre- and postoperative clinical data, VAS, and ODI scores. RESULTS: The average operative time in PETD group was 91.65 ± 14.04 min, and the average operative time in MPEID group was 65.41 ± 12.61 min (p < 0.001). In PETD group, the fluoroscopy occurrences averaged 9.71 ± 1.05 times, with fluoroscopy occurrences averaging 6.47 ± 1.00 times (p < 0.001) in MPEID group. At 12 months follow-up, the clinical effect showed significant improvement in both two groups. The MPEID group showed a decrease in average VAS-back score from 5.41 ± 2.18 to 1.76 ± 1.09 (p < 0.001) and VAS-leg score from 6.53 ± 1.66 to 0.82 ± 0.64 (p < 0.001). The ODI scores decreased from 51.35 ± 10.65 to 11.71 ± 2.91 (p < 0.001). In the PETD group, the VAS-back score decreased from 4.94 ± 1.98 to 2.06 ± 1.25 (p < 0.001), VAS-leg score from 7.12 ± 1.73 to 1.12 ± 0.60 (p < 0.001), and ODI scores from 48.00 ± 11.62 to 12.24 ± 2.56 (p < 0.001). According to the modified MacNab criteria, MPEID had 15 excellent and two good results; PETD had 12 excellent and 5 good (p = 0.23). No nerve root injuries, dural tears, or significant complications were reported. CONCLUSION: MPEID and PETD effectively treat L4/5 LDH, with MPEID showing shorter operative times and fewer fluoroscopies. Furthermore, the MPEID group can provide excellent clinical efficacy as the PETD group in the short term.

PMAIP1, a novel diagnostic and potential therapeutic biomarker in osteoporosis.

BACKGROUND: Osteoporosis is a common endocrine metabolic bone disease, which may lead to severe consequences. However, the unknown molecular mechanism of osteoporosis, the observable side effects of present treatments and the inability to fundamentally improve bone metabolism seriously restrict the impact of prevention and treatment. The study aims to identify potential biomarkers from osteoclast progenitors, specifically peripheral blood monocytes on predicting the osteoporotic phenotype. METHODS: Datasets were obtained from Gene Expression Omnibus (GEO). Based on the differentially expressed genes (DEGs) and GSEA results, GO and KEGG analyses were performed using the DAVID database and Metascape database. PPI network, TF network, drug-gene interaction network, and ceRNA network were established to determine the hub genes. Its osteogenesis, migration, and proliferation abilities in bone marrow mesenchymal stem cells (BMSCs) were validated through RT-qPCR, WB, ALP staining, VK staining, wound healing assay, transwell assay, and CCK-8 assay. RESULTS: A total of 63 significant DEGs were screened. Functional and pathway enrichment analysis discovered that the functions of the significant DEGs (SDEGs) are mainly related to immunity and metal ions. A comprehensive evaluation of all the network analyses, PMAIP1 was defined as osteoporosis's core gene. This conclusion was further confirmed in clinical cohort data. A series of experiments demonstrated that the PMAIP1 gene can promote the osteogenesis, migration and proliferation of BMSC cells. CONCLUSIONS: All of these outcomes showed a new theoretical basis for further research in the treatment of osteoporosis, and PMAIP1 was identified as a potential biomarker for osteoporosis diagnosis and treatment.

Evaluation of Safety and Efficacy of Preoperative Coronal MRI-Guided Minimally Invasive Surgery for Cervical Spondylotic Radiculopathy.

BACKGROUND Key-hole surgery is a minimally invasive technique that has shown promise in various surgical procedures. This study aimed to assess the clinical effectiveness of preoperative coronal MRI-assisted key-hole surgery for the treatment of patients with cervical spondylotic radiculopathy (CSR). MATERIAL AND METHODS A total of 30 patients diagnosed with CSR and undergoing key-hole surgery with CMRI assistance were included in the study. Various parameters, including surgical segments, incision length, disease duration, operative time, intraoperative fluoroscopy times, intraoperative blood loss, complications, and length of hospitalization, were recorded. Precise measurements of Cobb angles and intervertebral space height were taken before and after the surgical procedure. Surgical outcomes were evaluated using modified Macnab criteria, visual analogue scale (VAS), Japanese Orthopaedic Association Scores (JOA), and neck disability index (NDI). RESULTS The average duration of disease was 6.47±3.29 months, with an average incision length of 1.94±0.15 cm and operative time of 57.83±4.34 minutes. The average intraoperative blood loss was 33.70±9.28 ml, with an average of 3.50±0.73 intraoperative fluoroscopies. The average duration of hospitalization was 4.10±1.27 days. Preoperative and postoperative measurements showed no statistically significant difference in C2-C7 Cobb angles and intervertebral space height. However, there were significant improvements in postoperative VAS, NDI, and JOA scores compared to preoperative scores. The surgical effectiveness rate was 100%, with a high rate of good and excellent outcomes. CONCLUSIONS The findings of this study suggest that preoperative CMRI-assisted key-hole surgery for single-segment CSR is a safe and effective treatment option with low complication rates. The clinical benefits include high security and good outcomes. Further research and larger studies are warranted to validate these findings.

Risk Factors and Causes of Reoperation in Lumbar Disc Herniation Patients after Percutaneous Endoscopic Lumbar Discectomy: A Retrospective Case Series with a Minimum 2-Year Follow-Up.

BACKGROUND Percutaneous endoscopic lumbar discectomy (PELD) has gained popularity as a minimally invasive surgery for treating lumbar disc herniation. However, there is limited research focusing on the reoperation rate and its associated factors. This study aims to investigate the rate of reoperation and identify the causes and risk factors for reoperation after PELD. MATERIAL AND METHODS We conducted a retrospective analysis of patients who underwent PELD (interlaminar and transforaminal approaches) at our hospital from November 2016 to May 2020. A matched case-control design was employed to identify relevant risk factors for reoperation, with a matching ratio of 1:3. Clinical characteristics and radiological parameters were compared, and univariate analysis was performed using independent samples t-test and chi-squared test. RESULTS Among the 435 patients included in the study, the reoperation rate for those with a minimum 2-year follow-up was 6.2% (27/435). The causes of reoperation and their respective rates were as follows: recurrence of lumbar disc herniation (3.2%, 14/435), incomplete decompression (1.8%, 8/435), persistent low back pain (0.7%, 3/435), and postoperative infection (0.5%, 2/435). Univariate analysis revealed that age (P=0.015), Pfirrmann grade IV-V (P=0.017), and lack of active straight leg raise exercises (P=0.026) were significantly associated with reoperation. Multiple logistic regression analysis indicated that age (P=0.001), Pfirrmann grade IV-V (P=0.033), and lack of active straight leg raise exercises postoperatively (P=0.003) were independent risk factors for reoperation after PELD. CONCLUSIONS The primary cause of reoperation in lumbar disc herniation patients after PELD was recurrence of the herniation. Additionally, severe disc degeneration, older age, and lack of active straight leg raise exercises were identified as significant risk factors associated with an increased reoperation rate.

Case report: Traumatic lumbosacral spondyloptosis with locked L5 inferior articular process.

Background: Traumatic lumbosacral spondyloptosis is a very rare spinal disease caused by high-energy trauma. We report a case of traumatic lumbosacral spondyloptosis with locked L5 inferior articular process. Case presentation: A 33-year-old man presented with multisite pain for 6 h following waist trauma and was admitted to the hospital. He suffered multiple injuries from severe impact on the waist after driving an out of control forklift truck. Preoperative imaging examinations revealed that the patient was diagnosed with traumatic lumbosacral spondyloptosis and the L5 inferior articular process was locked into the anterior margin of the S1 vertebra. A posterior instrumentation, decompression of the cauda equina, and interbody fusion procedure was performed. The patient received hyperbaric oxygen and rehabilitation treatment 10 days after the surgery. At the 6-month postoperative follow-up, the muscle strength of the lower limbs was improved, the patient had no numbness of both lower limbs, and the urinary retention symptom was significantly improved. The American Spinal Injury Association grade improved from grade C preoperatively to grade D postoperatively. As far as we know, there have been no relevant reports on traumatic lumbosacral spondyloptosis with locked L5 inferior articular process yet. Conclusion: We believe that the hyperflexion and shear forces were the potential causes of this injury. In addition, the preoperative imaging examinations should be evaluated carefully. If the inferior articular process of L5 were locked, we suggest removing the bilateral inferior articular processes first and then perform reduction.

Accuracy of Coronal Magnetic Resonance Imaging Diagnosis of Multi-Segmental Lumbar Disc Herniation: A Single-Center Retrospective Analysis.

BACKGROUND Multi-segment herniation of lumbar intervertebral discs is a complex lumbar spine disease, and it is difficult to identify the responsible segment using only magnetic resonance imaging (MRI). The present study screened 47 patients with multi-segment lumbar disc herniation (MSLDH) to evaluate coronal magnetic resonance imaging (CMRI) of three-dimensional fast-field echo with water-selective excitation to identify the responsible segment of multi-segment lumbar disc herniation (MSLDH) and to assess the accuracy and utility of CMRI. MATERIAL AND METHODS This retrospective study included 44 patients with low back pain or lower-extremity symptoms from January 2019 to December 2021. The imaging (including CMRI) and clinical data of the patients were analyzed by 3 independent, blinded experts. The Kappa statistical method was used to characterize the reader-to-reader reliability to qualitatively evaluate the data. RESULTS CMRI showed high diagnostic performance, with 90.2% sensitivity, 94.9% positive predictive value (PPV), 80% negative predictive value (NPV), and 83.4% accuracy, and there were significant differences in hospital length of stay (P=0.013) and surgical bleeding (P=0.006) (P<0.01) between single-segment and multi-segment patients. CONCLUSIONS CMRI is highly accurate in revealing the shape, signal, and position of the intraspinal and extraspinal lumbosacral plexus, and reducing surgical segments can help improve postoperative outcomes for patients.

Analysis and verification of the circRNA regulatory network RNO_CIRCpedia_ 4214/RNO-miR-667-5p/Msr1 axis as a potential ceRNA promoting macrophage M2-like polarization in spinal cord injury.

BACKGROUND: CircRNAs are involved in the pathogenesis of several central nervous system diseases. However, their functions and mechanisms in spinal cord injury (SCI) are still unclear. Therefore, the purpose of this study was to evaluate circRNA and mRNA expression profiles in the pathological setting of SCI and to predict the potential function of circRNA through bioinformatics. METHODS: A microarray-based approach was used for the simultaneous measurement of circRNAs and mRNAs, together with qPCR, fluorescence in situ hybridization, western immunoblotting, and dual-luciferase reporter assays to investigate the associated regulatory mechanisms in a rat SCI model. RESULTS: SCI was found to be associated with the differential expression of 414 and 5337 circRNAs and mRNAs, respectively. Pathway enrichment analyses were used to predict the primary function of these circRNAs and mRNAs. GSEA analysis showed that differentially expressed mRNAs were primarily associated with inflammatory immune response activity. Further screening of these inflammation-associated genes was used to construct and analyze a competing endogenous RNA network. RNO_CIRCpedia_4214 was knocked down in vitro, resulting in reduced expression of Msr1, while the expression of RNO-miR-667-5p and Arg1 was increased. Dual-luciferase assays demonstrated that RNO_CIRCpedia_4214 bound to RNO-miR-667-5p. The RNO_CIRCpedia_4214/RNO-miR-667-5p/Msr1 axis may be a potential ceRNA that promotes macrophage M2-like polarization in SCI. CONCLUSION: Overall, these results highlighted the critical role that circRNAs may play in the pathophysiology of SCI and the discovery of a potential ceRNA mechanism based on novel circRNAs that regulates macrophage polarization, providing new targets for the treatment of SCI.

Does Percutaneous Endoscopic Lumbar Discectomy for Adolescent Posterior Ring Apophysis Fracture Accompanied with Lumbar Disc Herniation Have Better Outcome Than Lumbar Disc Herniation Alone?

Objective: This study aims to compare the efficacy of percutaneous endoscopic lumbar discectomy (PELD) in treating adolescent posterior ring apophysis fracture (APRAF) accompanied by lumbar disc herniation (LDH) and lumbar disc herniation alone. Methods: Herein we present a case series of adolescent patients who underwent PELD surgery from June 2017 to September 2021. All patients were divided into two distinct groups (ie Group A and B), based on their preoperative Computed tomography (CT) scans. Group A included patients with PRAF (type III) accompanied by LDH. Group B patients had LDH alone. The general clinical characteristics, clinical outcomes, and complications in patients from the two groups were assessed and compared. Results: Compared to before surgery, the back and leg visual analog scores (VAS) and Oswestry Disability Index (ODI) were markedly improved in both groups' patients at all follow-ups. Notably, no significant differences were observed in the back and leg VAS scores, and ODI values between the two groups at different time points after surgery. The mean intraoperative blood loss was significantly lower in Group B, relative to Group A. The mean operation time was significantly shorter in Group B, compared to Group A. There was no statistically significant difference in complication and recurrence rates between the two groups. Conclusion: APRAF (type III) accompanied by LDH and LDH alone can obtain roughly equal surgical effects through PELD surgery and turns out to be a safe and effective surgical approach.

Unilateral Biportal Endoscopic Discectomy versus Percutaneous Endoscopic Lumbar Discectomy for Lumbar Disc Herniation: A Systematic Review and Meta-analysis.

BACKGROUND: Unilateral biportal endoscopic discectomy (UBED) is a novel and minimally invasive surgery for lumbar disc herniation (LDH). However, efficacy and safety of UBED compared to the conventional percutaneous endoscopic lumbar discectomy (PELD) remains to be determined. A meta-analysis was performed in this study to compare between UBED and PELD for LDH. METHODS: Relevant cohort studies were found by searching Medline, Web of Science, Embase, Wanfang, and CNKI from database inception to October 13, 2022. Results were pooled using a random-effects model incorporating heterogeneity. RESULTS: In this meta-analysis, 12 studies involving 1175 patients with LDH were included. Pooled results showed that compared with PELD, UBED was associated with a longer surgery time (mean difference [MD] 17.62 min, P < 0.001) and hospital stay (MD 1.40 day, P = 0.04). However, UBED and PELD showed comparative efficacies in improving the Visual Analogue Scale of leg and back, and Oswestry Disability Index, scores. The incidence of perioperative complications was not significantly different between the 2 procedures (risk ratio [RR] 1.62, P = 0.25), while UBED was associated with a lower LDH recurrence during follow-up (RR 0.29, P = 0.03). CONCLUSIONS: Although UBED is associated with longer surgery time and hospital stay, it shows similar efficacy to PELD in relieving pain and improving functional ability in patients with LDH. In addition, limited evidence suggests that UBED may be associated with a lower LDH recurrence as compared to PELD, while the incidence of perioperative complications is not different. These findings support UBED as a treatment for patients with LDH.

Percutaneous endoscopic interlaminar discectomy for posterior ring apophyseal fracture accompanied with lumbar disc herniation in a 12-year pediatric diver: a case report.

BACKGROUND: Posterior ring apophysis fracture (PRAF), accompanied with lumbar disc herniation (LDH), is a rare occurrence. Owing to its rarity, there is no consensus on the treatment strategy for this condition. Differences mainly encompass the type of decompression method, the need for additional spinal fusion, the need for apophysis fragments or/and disc materials removal, and long-term efficacy, particularly, compared to LDH alone. Hence, the aim of this study was to describe a rare instance of PRAF with LDH in a 12-year-old professional diver, who was successfully treated with percutaneous endoscopic interlaminar discectomy (PEID), and to initiate a discussion involving several meaningful and related factors.

The application of antidepressant drugs in cancer treatment.

Antidepressants refer to psychotropic drugs which are used to treat mental illness with prominent emotional depression symptoms. It was reported that antidepressants had associated with anti-carcinogenic function which was associated with various signaling pathways and changing of microenvironment. Its mechanism includes cell apoptosis, antiproliferative effects, mitochondria-mediated oxidative stress, DNA damaging, changing of immune response and inflammatory conditions, and acting by inhibiting multidrug resistance of cancer cells. Accumulated studies showed that antidepressants influenced the metabolic pathway of tumor cells. This review summarized recent developments with the impacts and mechanisms of 10 kinds of antidepressants in carcinostasis. Antidepressants are also used in combination therapy with typical anti-tumor drugs which shows a synergic effect in anti-tumor. By contrast, the promotion roles of antidepressants in increasing cancer recurrence risk, mortality, and morbidity are also included. Further clinical experiments and mechanism analyses needed to be achieved. A full understanding of the underlying mechanisms of antidepressants-mediated anticarcinogenic effects may provide new clues for cancer prevention and clinical treatment.

Risk Factors Involved in the Early and Medium-Term Poor Outcomes of Percutaneous Endoscopic Transforaminal Discectomy: A Single-Center Experience.

Objective: To investigate the risk factors involved in the early and medium-term poor outcomes of percutaneous endoscopic transforaminal discectomy (PETD) treatment of lumbar disc herniation (LDH) at the L4-5 level. Methods: Between January 2015 and May 2020, we recruited 148 LDH patients at the L4-5 level who underwent PETD surgery. The patients were divided into Groups A and B, according to the surgical outcomes. Good and excellent outcomes were categorized into Group A, and generally good and poor outcomes were categorized into Group B. Clinical parameters (age, gender, symptom duration, hospital stay, operation time, blood loss, straight-leg raising (SLR), visual analog scale (VAS), Oswestry Disability Index (ODI) score and modified MacNab criteria) and radiologic parameters (foraminal height (FH), intervertebral height index (IHI), intervertebral angle (IVA), sagittal range of motion (sROM), and lumbar lordosis (LL)) were collected and analyzed using univariate and multiple logistic regression analyses. Results: At the 6-month follow-up post operation, univariate analysis revealed that the symptom duration, SLR, IHI, and sROM were strongly associated with poor outcomes. However, multiple logistic regression analysis demonstrated that prolonged symptom duration, large SLR angel, and large sROM were independent risk factors for poor outcomes. At the 2-year follow-up post operation, univariate analysis suggested that advanced age, prolonged symptom duration, large preoperative VAS score, small FH, small IHI, and large sROM were potential risk factors for poor outcomes. However, multiple logistic regression analysis demonstrated that prolonged symptom duration, small IHI, and large sROM were independent risk factors for poor outcomes. Conclusion: Our study demonstrated that prolonged symptom duration, large SLR angel, and large sROM were independent risk factors for poor outcomes immediately following PETD at the L4-5 level. However, prolonged symptom duration, small IHI, and large sROM were independent risk factors for poor outcomes at medium-term post PETD at the L4-5 level.

Percutaneous Endoscopic Interlaminar Discectomy via Laminoplasty Technique for L5 -S1 Lumbar Disc Herniation with a Narrow Interlaminar Window.

OBJECTIVE: To improve the treatment effect of patients with L5 S1 lumber disc herniation (LDH) with a narrow interlaminar window, we proposed an alternative approach to percutaneous endoscopic interlaminar discectomy (PEID) via the laminoplasty technique. METHODS: Fifteen L5 S1 LDH patients (7 men and 8 women; age range, 22 to 56 years; median age, 34 years; 9 left, 6 right) were enrolled in the present study retrospectively. The interlaminar windows of all patients were narrow (the transverse diameter of the L5 S1 interlaminar window is equal to or less than that of L4-5 ). Percutaneous laminoplasty and endoscopic interlaminar discectomy surgery were undergone by all patients from July 2018 to July 2019. All operations were completed under local anesthesia. The target laminoplasty area was the safety zone, use of which avoids both transverse and exit nerve roots. Under fluoroscopic guidance or clear endoscopic visualization, the trephines were used to enlarge the interlaminar window, which allowed the working cannula to enter the spinal canal but avoid nerve roots and the dural sac. The preoperative/postoperative visual analogue scale (VAS) scores and Oswestry disability index (ODI) were statistically analyzed. The modified MacNab criterion was used to assess the clinical effects. The radiological outcomes were evaluated by MRI and CT. SPSS 19.0 software was used for the statistical evaluation. RESULTS: The operative time ranged from 70 to 120 min, with a median time of 92 min, and the fluoroscopy times ranged from 8 to 12, with a median of 9.7 times. The body mass index (BMI) of patients ranged from 18.10 to 26.06, with a median of 22.04. All patients were followed up in the outpatient department for at least 12 months after surgery. At the last follow up, the average VAS-Back score of the study patients was reduced from 5.33 ± 2.09 to 2.00 ± 1.20 (P < 0.001) and the average VAS-Leg score was reduced from 7.53 ± 1.69 to 1.47 ± 0.92 (P < 0.001). The average ODI scores improved from 47.87 ± 11.41 to 12.93 ± 3.24 (P < 0.01). According to the modified MacNab criteria, 11 cases achieved excellent results and 4 cases achieved good results. All of the operations were successful. There wertr no nerve root injuries, dural tears, or other complications. CONCLUSION: The laminoplasty approach for PEID provides a safe and useful alternative for the treatment of L5-S1 LDH patients with a narrow interlaminar window.

Meta-analysis of the operative treatment of lumbar disc herniation via transforaminal percutaneous endoscopic discectomy versus interlaminar percutaneous endoscopic discectomy in randomized trials.

BACKGROUNDS: Transforaminal percutaneous endoscopic discectomy (TF-PELD) and interlaminar percutaneous endoscopic discectomy (IL-PELD) are the most common alternative treatments of lumbar disc herniation. The aim of this study was to compare the operation time duration and X-ray exposure as well as outcomes of TF-PELD and IL-PELD as indicated by the published clinical evidences within randomized trials. METHODS: We included randomized, controlled studies reporting operation duration and X-ray exposure as well as clinical outcome evaluations, comparing TF-PELD to IL-PELD with a minimum of 10 patients per group. The included data measures were operation duration, X-ray exposure and postoperation evaluations. Data were synthesized and analyzed using ReviewManager version 5.3. Publication bias was evaluated via funnel plot. The Cochran Q test and the degree of inconsistency (I2) were used to assess heterogeneity. Lowly biased and heterogenous dichotomous data were calculated by odds ratio and continuous data were calculated by mean difference (MD) with 95% confidence intervals (CI). RESULTS: Thirteen studies published from January 1970 to March 2018, with a total of 770 lumbar disc herniation patients, including 361 cases of TF-PELD and 409 cases of IL-PELD, were finally included. Meta-analysis of data extracted from these studies revealed that the postoperation outcomes of both surgery methods did not differ significantly, but the surgery duration was significantly shorter in the IL-PELD group than in the TF-PELD group (MD 21.69; 95% CI 12.94-30.27; P = .00001), and the fluoroscopy times demanded in the IL-PELD group was significantly fewer than those in the TF-PELD group (MD 7.57; 95% CI 6.22-8.93; P = .00001). CONCLUSION: The main finding of the study is that IL-PELD approach can decrease radiation exposure as their demanded duration of operation and fluoroscopy times were significantly shorter and fewer in the IL-PELD group, which they achieve similar outcomes comparing to TF-PELD. The study is limited at a lack of samples with lumbar disc herniation levels out of L5/S1. The findings implicate selection of IL-PELD approach over TF-PELD at applicable circumstances for lower lumbar disc herniation. Physicians should consider this data when choosing between TF-PELD and IL-PELD.

The bone marrow-derived mesenchymal stem cells (BMSCs) alleviate diabetic peripheral neuropathy induced by STZ via activating GSK-3ß/ß-catenin signaling pathway.

BACKGROUND: Diabetic peripheral neuropathy, a common complication of diabetic mellitus, has brought a threaten on patients' health. The bone marrow-derived mesenchymal stem cells (BMSCs) were reported to play an important role in diverse diseases. Nevertheless, the specific function of BMSCs in diabetic peripheral neuropathy remained uncharacterized. METHODS: A wide range of experiments including RT-qPCR, western blot, H&E staining, oxidative stress assessment, measurement of thermal sensitivity, ELISA, urine protein and CCK-8 assays were implemented to explore the function and mechanism of BMSCs in vivo and vitro. RESULTS: The experimental results displayed that BMSCs improve STZ-induced diabetes symptoms in rats by decreasing blood glucose and urinary protein. Functionally, BMSCs ameliorate oxidative stress, painful diabetic neuropathy, neurotrophic status and angiogenesis in STZ-induced rats. Moreover, BMSCs participate in the regulation of sciatic neuro morphology in diabetic neuropathy rat model. In mechanism, BMSCs alleviate diabetic peripheral neuropathy via activating GSK-3ß/ß-catenin signaling pathway in rats and improve Schwann's cells viability by activating GSK-3ß/ß-catenin signaling pathway under high glucose. CONCLUSIONS: We verified that BMSCs alleviate diabetic peripheral neuropathy of rats induced by STZ via activating GSK-3ß/ß-catenin signaling pathway, which implied a novel biomarker for diabetic peripheral neuropathy treatment.