Intervertebral disc degeneration (IVDD) is a primary cause of low back pain, with its molecular mechanisms remaining incompletely understood. Ubiquitin-conjugating enzymes (E2 enzymes) play critical roles in protein degradation and maintenance of cellular homeostasis, yet their expression profiles and functional significance in IVDD remain largely unexplored. Using Gene Expression Omnibus (GEO) datasets (GSE70362 and GSE23130), we performed differential expression analysis, intersected with ubiquitination-related genes, and applied weighted gene co-expression network analysis (WGCNA) to identify key E2 enzymes in IVDD. Single-cell RNA sequencing (GSE251686) characterized UBE2Q2 expression in intervertebral disc cell subpopulations. qRT-PCR, Western blot, immunohistochemistry, and immunofluorescence validated UBE2Q2 expression in human degenerated nucleus pulposus (NP) tissues and in vitro rat NP cell degeneration models. Bioinformatics analyses showed significant UBE2Q2 upregulation in IVDD, with WGCNA identifying it as a hub gene closely associated with degeneration. Consistently, single-cell data confirmed predominant UBE2Q2 expression in NP cells, with markedly higher levels in IVDD (p < 0.05). Moreover, experimental validation consistently demonstrated elevated UBE2Q2 mRNA and protein in degenerated human NP tissues and rat models, with stronger immunohistochemical and immunofluorescent signals in degenerated samples (p < 0.05). This study represents the first identification of UBE2Q2 as a potential biomarker and a new molecular target for IVDD, thereby providing a foundation for future functional and mechanistic investigations.
ObjectiveRevision surgery for the removal of a migrated interbody fusion cage is challenging due to scar tissue formation in the surgical area. This study introduces a unilateral biportal endoscopic (UBE) technique for the removal of a migrated fusion cage and reports the patient's clinical outcomes.MethodsA unilateral lumbar interbody fusion (ULIF) was performed via a trans-facet approach to extract the posterior lumbar interbody cage, thereby bypassing scar tissue from prior surgeries.ResultsThe patient's clinical symptoms improved significantly postoperatively, with no complications such as nerve injury or cerebrospinal fluid leakage. At the six-month postoperative follow-up, the patient's lumbar and leg VAS scores showed significant improvement, with no obvious signs of cage loosening observed.ConclusionUBE revision surgery may represent a safe and effective alternative for the removal of migrated posterior lumbar interbody cages.
BACKGROUND CONTEXT:The paraspinal muscles play a critical role in maintaining lumbar spine stability, and different muscles may have varying impacts on lumbar disc degeneration (LDD). However, studies exploring these relationships remain relatively limited. PURPOSE:This study aimed to investigate the relationship between various paravertebral muscles and LDD and to develop and validate a predictive model for LDD using machine learning (ML). STUDY DESIGN:Retrospective cohort study. PATIENT SAMPLE:A retrospective analysis was performed on hospitalized patients who underwent computed tomography (CT) and magnetic resonance imaging (MRI) examinations for chronic low back pain from February 2018 to January 2023. OUTCOME MEASURES:The primary outcome measures included model performance metrics such as receiver operating characteristic (ROC) curves, accuracy, sensitivity, specificity, F1 score, positive predictive value (PPV), negative predictive value (NPV), and calibration curves. Clinical decision-making benefits were assessed using decision curve analysis (DCA). Secondary outcome measures focused on model interpretability, evaluated through SHapley Additive exPlanations (SHAP), which identified key predictors and quantified their contributions to LDD prediction. METHODS:This study enrolled 518 patients as the internal cohort, who were randomly assigned to a training set (70%) and a test set (30%). The Synthetic Minority Oversampling Technique (SMOTE) was applied to mitigate class imbalance in the training set. Model parameters were optimized using grid search and 10-fold cross-validation to develop four machine learning models: Extreme Gradient Boosting (XGBoost), Random Forest (RF), Logistic Regression (LR), and Decision Tree (DT). External validation was performed using data from 343 patients from different tertiary medical centers. Paraspinal muscle parameters on lumbar spine CT and MRI images were measured using ImageJ, and LDD was evaluated based on the Pfirrmann grading system. Spearman correlation analysis and logistic regression were performed to assess factors associated with LDD. Model performance was evaluated using metrics such as ROC curves, accuracy, sensitivity, F1 score, PPV, NPV, calibration curves, and DCA. The SHAP method was employed to interpret the ML models. RESULTS:This study included a total of 861 patients for analysis. In the external validation cohort, the XGBoost model demonstrated the best performance, achieving an AUC of 0.880 (95% CI: 0.826-0.935). Its accuracy (0.819), specificity (0.841), and positive predictive value (PPV=0.958) outperformed other models. Notably, it also exhibited superior sensitivity (0.814) and F1-score (0.880). SHAP analysis further revealed that age, the psoas muscle index (PMI), and the functional cross-sectional area (fCSA) of the multifidus muscle were critical predictors of LDD. CONCLUSION:In this study, an LDD prediction model was developed using paravertebral muscle quantitative data and ML algorithms, with SHAP analysis incorporated to enhance model interpretability. The XGBoost model demonstrated the best predictive performance and holds potential to guide early clinical prevention and treatment.
OBJECTIVE:Sarcopenia, as a condition of muscle mass loss and functional decline typically diagnosed in elderly individuals, severely affects human physical activity, metabolic homeostasis, and quality of life. Gui Qi Zhuang Jin Decoction (GQZJD), an approved hospital-based prescription with years of clinical application, has been demonstrated to have a notable therapeutic effect on sarcopenia. However, its potential mechanism of action in the treatment of sarcopenia remains uncertain. METHODS:Ultra-performance liquid chromatography paired with Q Exactive™ HF-X mass spectrometry (UPLC-QE-MS) was used to identify the ingredients of GQZJD. Subsequently, GQZJD observed the basic growth and muscles of the sarcopenia mouse, while the behavioral indicators were also tested. Muscle histopathology and serum oxidative stress biochemicals were also detected, and mitochondrial function and energy metabolism-related indicators in the gastrocnemius muscle were examined. Then, a metabolomics strategy was applied to predict possible pathways involving mitochondria by which GQZJD could improve sarcopenia. Finally, quantitative real-time polymerase chain reaction and western blot analyses were carried out to validate the effects of GQZJD on sarcopenia-induced mitochondrial dysfunction, together with uncovering the associated mechanisms. RESULTS:Twenty-seven ingredients absorbed into the blood (IAIBs) of GQZJD were identified using UPLC-QE-MS, which were regarded as the main active ingredients behind its sarcopenia treatment effects. GQZJD administration increased the body weight, gastrocnemius muscle mass, and autonomic activity, mitigated muscle tissue morphology and pathology; and alleviated the oxidative stress levels in sarcopenia mice. Treatment with GQZJD also decreased the mitochondrial reactive oxygen species level and serum lipid peroxide Malonaldehyde concentration. and increased the mitochondrial membrane potential, adenosine triphosphate level, 8‑hydroxy-2-deoxyguanosine content, mitochondrial DNA copy number, and the mitochondrial fission factor dynamin-related protein 1. Non-targeted metabolomics suggested that the sarcopenia therapeutic effect of GQZJD on sarcopenia may occur through the glycerophospholipid metabolism, choline metabolism in cancer, phenylalanine metabolism and tyrosine metabolism pathways, implying an association with AMP-activated protein kinase (AMPK) and related signals. Further, the molecular docking results hinted that AMPK performed well in terms of binding energy with the 27 IAIBs of GQZJD (average binding energy, -7.5 kcal/mol). Finally, we determined that GQZJD significantly activated the key targets of the AMPK/peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)/nuclear factor erythroid 2-related factor 2 (Nrf2) axis.. CONCLUSIONS:Our results demonstrated that GQZJD ameliorated d-galactose-induced sarcopenia by promoting the animal behaviours, facilitating mitochondrial function and restoring mitochondrial energy metabolism. with its effects mediated by the AMPK/PGC-1α/Nrf2 axis. Over all, GQZJD represents a promising therapeutic candidate that ameliorated sarcopenia in aging mice.
OBJECTIVE:We aimed to preliminarily explore the efficacy and safety of unilateral biportal endoscopy for the treatment of epidural cement leaks. We report a patient who underwent epidural cement leakage removal and achieved endoscopic spinal decompression. METHODS:A 67-year-old female patient underwent biportal endoscopic paraspinal decompression following percutaneous vertebroplasty for an osteoporotic fracture that resulted in neurologic impairment due to epidural cement leakage. A transforaminal biportal endoscopic surgery was performed to remove the leaked cement, and the left L1 and bilateral L2 nerves were decompressed. RESULTS:The patient's postoperative clinical course was uneventful. CONCLUSIONS:A paraspinal approach that avoids a posterior approach reduces the need to remove stabilizing facet bone, is truly minimally invasive and does not involve an instrumented fusion, maybe a helpful addition in the minimally invasive spine surgeon's armamentarium.
OBJECTIVE:To investigate the clinical efficacy of posterior unilateral biportal endoscopic(UBE) cervical discectomy for cervical radiculopathy under general anesthesia. METHODS:A retrospective analysis of 35 patients with cervical disc herniation uderwent posterior UBE cervical discectomy under general anesthesia from March 2021 to March 2023 was performed, including 17 males and 18 females, with an average age of (56.00±7.79) years old ranging from 42 to 69 years old. The non-operative treatment time was 6 to 27 weeks with an average of(16.03±4.56) weeks. MRI showed lateral cervical disc herniation in 19 cases and foraminal cervical disc herniation in 8 cases. The pathological segments distribution was as follows L4,5 in 5 cases, C5,6 in 12 cases C6,7 in 18 cases. CT/MRI was performed 1 to 3 d after surgery to evaluate the decompression, and the visual analogue scale(VAS), the Japanese Orthopedic Association(JOA) score, the stability of cervical spine surgery segment and the change of intervertebral height were recorded. RESULTS:All 35 patients successfully completed the operation, and the operation time was (55.88±5.02) min, the hospital stay after surgery (3.53±0.74) d. All 35 patients were followed up from 12 to 24 months with an average of (14.53±2.32) months. The VAS of preoperative, postoperative 1 day and 12 months were (7.000±0.875), (2.540±0.611), (2.143±0.772), respectively, the VAS at each time point before and after surgery were statistically significant(P<0.05). The JOA scores of preoperative, postoperative 1 day and 12 months were (11.660±0.533), (16.430±0.655), (16.540±0.611), respectively. The intervertebral height of the lesion segment at preoperative and 12 months was (6.206±0.493) mm and (6.147±0.497) mmm, respectively, and the difference was not statistically significant(P>0.05). None of the patients had cervical spine segment instability before or after surgery. According to the modified Macnab criteria, the clinical efficacy was evaluated at 12 months after operation, 32 cases were excellent, 2 cases were good, and 1 case was good. CONCLUSION:UBE cervical discectomy is a minimally invasive, safe and effective surgical method for the treatment of single-segment cervical disc herniation, which may be an alternative to the treatment of cervical foraminal herniation, but due to the small sample size and short follow-up time, its long-term efficacy needs to be further observed.
OBJECTIVE: To evaluate the preliminary outcomes and clinical efficacy of a novel posterior biportal endoscopic technique in the treatment of central cervical disc herniation (CCDH). METHODS: A total of 11 patients with symptomatic CCDH who met the inclusion criteria underwent posterior biportal endoscopic discectomy between December 2021 and May 2023. The surgical procedure involved flavectomy, foraminotomy, pediculoplasty, and discectomy using 30 degrees and 45 degrees arthroscopes and specialized minimally invasive tools. Functional outcomes were assessed using the Japanese Orthopedic Association scoring system, Neck Disability Index, and visual analog scale for axial neck pain. Clinical efficacy was evaluated at the final follow-up using the modified Macnab criteria. RESULTS: All 11 patients successfully underwent posterior biportal endoscopic discectomy with a mean operative time of 82.7 +/- 10.1 minutes and mean estimated blood loss of 31.8 +/- 9.8 ml. The mean hospital stay was 5.2 +/- 1.1 days, and the mean follow-up period was 13.8 +/- 2.4 months. Significant improvements were observed in Neck Disability Index, Japanese Orthopedic Association, and visual analog scale scores. Clinical efficacy was rated as excellent in 3 patients, good in 6 patients, and fair in 2 patients according to the modified Macnab criteria. No cases of cervical instability or kyphosis were observed during postoperative follow-up. CONCLUSIONS: The novel posterior biportal endoscopic technique demonstrated significant clinical efficacy and safety in treating CCDH, with marked improvements in clinical outcomes, rapid postoperative recovery, and a low incidence of complications.
BackgroundOsteoarthritis (OA) is a degenerative joint disease characterized by the breakdown of joint cartilage and underlying bone. Macrophages are a type of white blood cell that plays a critical role in the immune system and can be found in various tissues, including joints. Research on the relationship between OA and macrophages is essential to understand the mechanisms underlying the development and progression of OA.ObjectiveThis study was performed to analyze the functions of the IRF1-GCN5-SETD2-SMARCC1 axis in osteoarthritis (OA) development.MethodsA single-cell RNA sequencing (scRNA-seq) dataset, was subjected to a comprehensive analysis aiming to identify potential regulators implicated in the progression of osteoarthritis (OA). In order to investigate the role of IRF1 and SMARCC1, knockdown experiments were conducted in both OA-induced rats and interleukin (IL)-1β-stimulated chondrocytes, followed by the assessment of OA-like symptoms, secretion of inflammatory cytokines, and polarization of macrophages. Furthermore, the study delved into the identification of aberrant epigenetic modifications and functional enzymes responsible for the regulation of SMARCC1 by IRF1. To evaluate the clinical significance of the factors under scrutiny, a cohort comprising 13 patients diagnosed with OA and 7 fracture patients without OA was included in the analysis.ResultsIRF1 was found to exert regulatory control over the expression of SMARCC1, thus playing a significant role in the development of osteoarthritis (OA). The knockdown of either IRF1 or SMARCC1 disrupted the pro-inflammatory effects induced by IL-1β in chondrocytes, leading to a mitigation of OA-like symptoms, including inflammatory infiltration, cartilage degradation, and tissue injury, in rat models. Additionally, this intervention resulted in a reduction in the predominance of M1 macrophages both in vitro and in vivo. Significant epigenetic modifications, such as abundant H3K27ac and H3K4me3 marks, were observed near the SMARCC1 promoter and 10 kb upstream region. These modifications were attributed to the recruitment of GCN5 and SETD2, which are functional enzymes responsible for these modifications. Remarkably, the overexpression of either GCN5 or SETD2 restored SMARCC1 expression in rat cartilages or chondrocytes, consequently exacerbating the OA-like symptoms.ConclusionThis research postulates that the transcriptional activity of SMARCC1 can be influenced by IRF1 through the recruitment of GCN5 and SETD2, consequently regulating the H3K27ac and H3K4me3 modifications in close proximity to the SMARCC1 promoter and 10 kb upstream region. These modifications, in turn, facilitate the M1 skewing of macrophages and contribute to the progression of osteoarthritis (OA).The Translational Potential of this ArticleThe study demonstrated that the regulation of SMARCC1 by IRF1 plays a crucial role in the development of OA. Knocking down either IRF1 or SMARCC1 disrupted the pro-inflammatory effects induced by IL-1β in chondrocytes, leading to a mitigation of OA-like symptoms in rat models. These symptoms included inflammatory infiltration, cartilage degradation, and tissue injury. These findings suggest that targeting the IRF1-SMARCC1 regulatory axis, as well as the associated epigenetic modifications, could potentially be a novel approach in the development of OA therapies, offering new opportunities for disease management and improved patient outcomes.
Objective Unilateral biportal endoscopy (UBE)is a minimally invasive spine surgery with reduced traumatization of the posterior lumbar ligament and muscular structures. This study reports contralateral translaminar approach with UBE for highly down-migrated lumbar disc herniation (LDH). Methods Data of 32 patients with highly down-migrated LDH treated using UBE at our center from January 2020 to July 2022 were retrospectively analyzed. The operation time and perioperative complications were recorded, and the visual analog scale (VAS) of pain was recorded to evaluate the degree of lower back and extremity pain. The Oswestry disability index (ODI) was used to evaluate lumbar spine function. The modified MacNab score was used to evaluate clinical efficacy. Results All patients successfully underwent the operation, with a time range from 47 to 65 min and an average operation time of 56.09 ± 5.11 min. Overall, 17 and 15 were males and females, respectively, with ages ranging from 34 to 72 years and an average age of 56 ± 7.89 years. The postoperative follow-up period was 12–18 months, with an average of 14.9 ± 2.3 months. The postoperative lower back VAS pain score and ODI were statistically significant compared with preoperatively ( P < 0.05). At the final follow-up, according to the modified Macnab criteria, 90.6% of cases were classified as good or excellent. Conclusion UBE treatment of highly down-migrated LDH through the contralateral translaminar approach is safe and efficient. Therefore, this approach can be an efficient alternative for patients with highly downward-migrating LDH.
Abstract The prevalence of thyroid dysfunction diseases (TDFDs) and osteoporosis (OP) is high. Previous studies have indicated a potential association between TDFDs and OP, yet the causal direction remains unclear. This study aimed to investigate the potential causal relationship between TDFDs and the risk of developing OP and related fractures. We obtained pooled data from genome-wide association studies (GWASs) conducted on TDFDs and OP in European populations and identified single-nucleotide polymorphisms (SNPs) with genome-wide significance levels associated with exposure to TDFDs as instrumental variables. Inverse variance weighted (IVW) was employed as the primary method for Mendelian randomization (MR) analysis, supplemented by MR‒Egger, weighted median, simple mode and weighted mode methods. Sensitivity analyses were conducted to evaluate the robustness of the findings. The IVW method demonstrated an increased risk of OP in patients with TDFDs, including hyperthyroidism and hypothyroidism (TDFDs: OR = 1.11; 95% CI 1.09, 1.13; hypothyroidism: OR = 1.14; 95% CI 1.10, 1.17; hyperthyroidism: OR = 1.09; 95% CI 1.06, 1.12). These findings were supported by supplementary analysis, which revealed a positive correlation between TDFDs and the risk of OP. Multiple sensitivity analyses confirmed the absence of horizontal pleiotropy in the study, thus indicating the robustness of our results. The causal relationship between TDFDs and increased risk of OP implies the need for early bone mineral density (BMD) screening and proactive prevention and treatment strategies for individuals with TDFDs.
OBJECTIVE:To assess the feasibility and imaging outcomes of unilateral biportal endoscopic technique in the treatment of lumbar foraminal stenosis through contralateral approach.METHODS:The clinical data of 33 patients with lumbar foraminal stenosis treated with unilateral biportal endoscopic technique from January 2021 to July 2022 were retrospectively analyzed. There were 17 males and 16 females;age ranging from 34 to 72 years old with an average of (56.00±7.89) years old;operation time and perioperative complications were recorded;visual analogue scale (VAS) of pain was recorded, to evaluate the degree of low back pain and lower extremity pain, and Oswestry disability index (ODI) to evaluate the lumbar spine function. At the latest follow-up, the modified Macnab score was used to evaluate the clinical efficacy.RESULTS:All patients successfully completed the operation. The operation time ranged from 47 to 65 minutes, with an average of (56.10±5.19) minutes. The postoperative follow-up ranged from 12 to 18 months, with an average of (14.9±2.3) months. The VAS of low back and lower extermity pain before operation were (7.273±1.442) and (7.697±1.447) scores, ODI was (69.182±9.740)%. Postoperative lumbocrural pain VAS were (3.394±0.966) and (2.818±0.727) scores, ODI was (17.30±4.78) %. At the latest follow-up, VAS of back and lower extermity pain was (2.788±0.650) and (2.394±0.704) scores, ODI was (14.33±350)%. There were significant differences in VAS of low back and lower extremity pain and ODI before and after operation(P<0.05). At the latest follow-up, according to the modified Macnab criteria, 24 patients got excellent result, 5 as good, 2 as fair, and 2 as poor.CONCLUSION:Unilateral biportal endoscopic treatment of lumbar foraminal stenosis through the contralateral approach is a safe and efficient method, with few complications, quick postoperative recovery, and satisfactory clinical outcomes. During the follow-up period, no iatrogenic lumbar instability was observed.
In individuals afflicted with hemophilia, characterized by a deficiency of coagulation factor VIII (FVIII), the occurrence of spontaneous recurrent intra-articular hemorrhage precipitates the emergence of hemophilic arthropathy (HA). Although clotting factor replacement therapy reduces joint bleeding clinically, clotting factors need to be injected frequently due to the rapid diffusion of the drug. Hence, a novel drug delivery approach may be developed to improve the drug therapy. Platelet-derived extracellular vesicles (PEVs) are known to possess anti-inflammatory and hemostatic properties and could be used as a potential HA therapy. In this study, we constructed a PEV-LS@FVIII nanotherapeutic system by combining thioketal (TK), liposomes (LS), and FVIII to form the LS@FVIII complexes, and then hybridizing PEV with LS@FVIII. Our results demonstrated that PEV-LS@FVIII could efficiently facilitate FVIII delivery and specifically target the injured knee joint. Both in vitro and in vivo studies showed a reduction in the M1 phenotype of macrophages and an enhancement of the M2 phenotype, compared to FVIII free control. Furthermore, PEV-LS@FVIII appeared to alleviate HA-induced cartilage damage. In conclusion, our findings demonstrate that PEV-LS@FVIII could delay the progression of HA by targeting bleeding joints, modulating macrophage polarization to suppress inflammation, and mitigating cartilage damage.
Abstract Background Spindle cell sarcoma (SCS) is rare in clinical practice. The purpose of this study was to establish the nomograms to predict the OS and CSS prognosis of patients with SCS based on the Surveillance, Epidemiology, and End Results (SEER) database. Methods The data of patients with SCS were extracted from the SEER database between 2004 and 2020, and randomly allocated to the training cohort and validation cohort. Univariate and multivariate Cox regression analysis are used to screen for independent risk factors both in overall survival (OS) and cancer-specific survival (CSS). Nomograms for OS and CSS were established for patients with SCS based on the results of multivariate cox analysis. Then we validated the nomograms by Concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Finally, the Kaplan-Meier curve and log-rank test were performed to compare between the patients with SCS in three different levels and different treatment groups. Results A total 1369 patients with SCS were included and randomly divided into the training cohort (n = 961, 70%) and validation cohort (n = 408, 30%). Age, M, tumor size, tumor location, surgery and radiation were independent prognostic factors for OS, while Age, N, M, tumor size, tumor location and surgery for CSS by Cox regression analysis. The nomogram models were established based on the result of the Multiple Cox analysis both in OS and CSS. The C-index of the OS model was 0.79 and 0.77 in the training and validation group, while 0.80 and 0.78 for CSS. The 3/5-year AUCs were 0.817 and 0.824 for the training group and 0.798 and 0.792 for the validation group for OS, while 0.829 and 0.831 in the training group, 0.814 and 0.791 in the validation group for CSS. calibration curves showed high consistencies between the observed survival and the predicted survival both in OS and CSS. In addition, DCA analyzed the clinical practicality of OS and CSS nomogram models have good net benefit. Conclusion The two nomograms we have established are expected to accurately predicting personalized prognosis of SCS patients, which may beneficial for clinical decision-making.
OBJECTIVE:Low back pain (LBP) is a worldwide health issue primarily attributed to intervertebral disc degeneration (IVDD). Qiangjin Zhuang Qufeng mixture (QJZG), an approved hospital-based formula with years of clinical application, has demonstrated notable therapeutic effects in the treatment of LBP. Nevertheless, the underlying mechanism by which it alleviates LBP remains uncertain.METHODS:The bioactive constituents of QJZG were initially identified using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS). Subsequently, network pharmacology was employed to explore the core components and targets. In vivo and in vitro experiments were then conducted to validate the specific mechanism of action of QJZG based on the identified targets and pathways. Following that, ultra-high-performance liquid chromatography/mass spectrometry combined with 16S rRNA gene sequencing of blood and faecal samples was utilized to assess the impact of gut microbiota on faecal and serum metabolites subsequent to QJZG administration in intervertebral disc degeneration (IVDD) rats.RESULTS:The principal constituents of QJZG were identified using UPLC-Q-TOF-MS/MS, revealing a substantial enrichment of flavonoids and triterpenes. Network pharmacology analysis indicated the potential inhibitory effects of QJZG on the NLRP3 inflammasome and downstream inflammatory factors. Furthermore, investigations demonstrated that intervertebral disc degeneration may be attributed to pyroptotic cell death within the nucleus pulposus. In vitro experiments were performed utilizing LPS to induce the inflammatory response in nucleus pulposus cells (NPC), and it was observed that QJZG-containing serum significantly suppressed key pyroptosis-related genes and downstream inflammatory factors. Additionally, in vivo experiments substantiated the capacity of QJZG to preserve disc height and ameliorate the progression of disc degeneration. Concurrently, oral pharmacotherapy in animal studies prominently involved the effects of Enterobacteriaceae and Clostridium, closely intertwined with lipid metabolism.CONCLUSIONS:QJZG exhibited a delaying effect on IVDD by preserving the equilibrium between extracellular matrix (ECM) synthesis and degradation in NPCs. This effect was achieved through the suppression of NLRP3 inflammasome expression and the prevention of pyroptosis in NPCs.
To construct an injectable fibrin glue system loaded with kaempferol (FG@F) to improve the bioavailability of kaempferol and observe its efficacy in the treatment of intervertebral disc degeneration (IVDD). Kaempferol-loaded fibrin glue was first synthesized in advance. Subsequently, the materials were characterized by various experimental methods. Then, nucleus pulposus cells (NPCs) were stimulated with lipopolysaccharide (LPS) to establish a degenerative cell model, and the corresponding intervention treatment was conducted to observe the effect in vitro. Finally, the tail disc of rats was punctured to establish a model of IVDD, and the therapeutic effect of the material in vivo was observed after intervertebral disc injection. The FG@F system has good injectability, sustained release and biocompatibility. This treatment reduced the inflammatory response associated with IVDD and regulated matrix synthesis and degradation. Animal experimental results showed that the FG@F system can effectively improve needle puncture-induced IVDD in rats. The FG@F system has better efficacy than kaempferol or FG alone due to its slow release and mechanical properties. The drug delivery and biotherapy platform based on this functional system might also serve as an alternative therapy for IVDD.
Spindle cell sarcoma (SCS) is rare in clinical practice. The objective of this study was to establish nomograms to predict the OS and CSS prognosis of patients with SCS based on the Surveillance, Epidemiology, and End Results (SEER) database. The data of patients with SCS between 2004 and 2020 were extracted from the SEER database and randomly allocated to a training cohort and a validation cohort. Univariate and multivariate Cox regression analyses were used to screen for independent risk factors for both overall survival (OS) and cancer-specific survival (CSS). Nomograms for OS and CSS were established for patients with SCS based on the results of multivariate Cox analysis. Then, we validated the nomograms by the concordance index (C-index), receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Finally, Kaplan‒Meier curves and log-rank tests were applied to compare patients with SCS at three different levels and in different treatment groups. A total of 1369 patients with SCS were included and randomly allocated to a training cohort (n = 1008, 70%) and a validation cohort (n = 430, 30%). Age, stage, grade, tumour location, surgery, radiation and diagnosis year were found to be independent prognostic factors for OS by Cox regression analysis, while age, stage, grade, tumour location and surgery were found to be independent prognostic factors for CSS. The nomogram models were established based on the results of multivariate Cox analysis for both OS and CSS. The C-indices of the OS model were 0.76 and 0.77 in the training and validation groups, respectively, while they were 0.76 and 0.78 for CSS, respectively. For OS, the 3- and 5-year AUCs were 0.801 and 0.798, respectively, in the training cohort and 0.827 and 0.799, respectively, in the validation cohort; for CSS, they were 0.809 and 0.786, respectively, in the training cohort and 0.831 and 0.801, respectively, in the validation cohort. Calibration curves revealed high consistency in both OS and CSS between the observed survival and the predicted survival. In addition, DCA was used to analyse the clinical practicality of the OS and CSS nomogram models and revealed that they had good net benefits. Surgery remains the main treatment method for SCS patients. The two nomograms we established are expected to accurately predict the personalized prognosis of SCS patients and may be useful for clinical decision-making.
Objective: The purpose of this study was to compare the clinical and radiological outcomes of unilateral biportal endoscopic (UBE) and percutaneous posterior endoscopic cervical discectomy (PE) keyhole surgeries. Methods: Patients diagnosed with cervical spondylotic radiculopathy (CSR) treated by UBE or PE keyhole surgery from May 2017 to April 2020 were retrospectively analyzed. The length of incision, fluoroscopic time, postoperative hospital stay, and total cost were compared. The clinical efficacy was assessed using a visual analog scale (VAS), neck disability index (NDI), and modified MacNab criteria. Moreover, the C2-7 Cobb’s angle, range of motion (ROM), intervertebral height, vertebral horizontal displacement, and angular displacement of the surgical segment were measured. Results: A total of 154 patients were enrolled, including 89 patients in the UBE group and 65 patients in the PE group, with a follow-up period of 24–32 months. Compared with PE surgery, UBE surgery required shorter fluoroscopic times (6.76 ± 1.09 vs. 8.31 ± 1.10 s) and operation times (77.48 ± 17.37 vs. 84.92 ± 21.97 min) but led to higher total hospitalization costs and longer incisions. No significant differences were observed in the postoperative hospital stay, bleeding volume, VAS score, NDI score, effective rate, or complication rate between the UBE and PE groups. Both the C2-7 Cobb’s angle and ROM increased significantly after surgery, with no significant differences between groups. There were no significant differences between intervertebral height, vertebral horizontal displacement, and angular displacement of the surgical segment at different times. Conclusions: Both UBE and PE surgeries in the treatment of CSR were effective and similar after 24 months. The fluoroscopic and operation times of UBE were shorter than those of PE.
Objective: The objective of this study was to introduce a surgical technique for the percutaneous decompression of cervical stenosis (CS) using a unilateral biportal endoscopic approach and characterize its early clinical and radiographic results. Materials and Methods: Nineteen consecutive patients with CS who needed surgical intervention were recruited. All enrolled patients underwent unilateral biportal endoscopic laminectomy (UBEL). All patients were followed postoperatively for >1 year. The preoperative and final follow-up evaluations included the Japanese Orthopedic Association (JOA) score for neurological assessment, visual analogue scale (VAS) for axial pain and C2–C7 Cobb angle for cervical sagittal alignment. The postoperative complications were analyzed. Results: Thirteen males and six females were included in the analysis. The mean follow-up period was 16.3 ± 2.6 months. The mean operative time was 82.6 ± 18.4 min. Postoperative MRI and CT revealed ideal neural decompression of the treated segments in all patients. Preoperative VAS and JOA scores improved significantly after the surgery, and cervical lordosis was preserved on the postoperative images. Conclusions: UBEL was an effective surgical method for CS, which may also minimize iatrogenic damage to the posterior tension band (PTB) and help to maximize the preservation of the cervical lordosis.
To construct an injectable, sustained-release fibrin gel containing rhein to solve the problem of low bioavailability of rhein, and observe its efficacy in the treatment of intervertebral disc degeneration. The fibrin gel containing rhein was first synthesized in advance. Subsequently, the materials were characterized by various experimental methods. Secondly, the degenerative cell model was constructed by stimulating nucleus pulposus cells with lipopolysaccharide (LPS), and the corresponding intervention treatment was carried out to observe the effect in vitro. Finally, the rat tail intervertebral disc was acupunctured by needles to establish the intervertebral disc degeneration model, and the effect of the material was observed through intradiscal injection. The fibrin glue containing rhein (rhein@FG) showed good injectability, sustained release and biocompatibility. Rhein@FG can improve the LPS-induced inflammatory microenvironment, regulate ECM metabolic disorders of nucleus pulposus cells and aggregation of the NLRP3 inflammasome in vitro, and inhibit cell pyroptosis. Furthermore, in vivo experiments, rhein@FG effectively prevented needle puncture-induced intervertebral disc degeneration in rats. Rhein@FG has better efficacy than rhein or FG alone due to its slow release and mechanical properties, which can be used as a potential replacement therapy for intervertebral disc degeneration.