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PURPOSE: Introducing a suture repair technology, endoscopic double line suture repair technique, for iatrogenic dural injury during Percutaneous Endoscopic Lumbar Discectomy (PELD) surgery. METHODS: A patient with dural injury and cauda equina herniation during PELD surgery was treated with endoscopic double line suture repair technique. RESULTS: A patient with dural injury and cauda equina nerve herniation during PELD surgery was successfully treated using double-line suture technique. After the repair, no obvious cerebrospinal fluid leakage and cauda equina nerve re-herniation was seen. During the postoperative observation period, the wound healed well and there were no complications related to cerebrospinal leakage. During the follow-up period (1 year), the patient reported significant symptom relief and no complications. CONCLUSION: This novel dural repair technology is safe and effective and can be used to treat dural injuries during PELD surgery.
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Osteosarcoma is a primary solid bone malignancy, and surgery + chemotherapy is the most commonly used treatment. However, chemotherapeutic drugs can cause a range of side effects. Casticin, a polymethoxyflavonoid, has anti-tumor therapeutic effects. This study is aim to investigate the anti-osteosarcoma activity of casticin and explore the mechanism. Crystal violet staining, MTT assay, colony formation assay, wound healing assay, transwell assay, hoechst 33,258 staining, and flow cytometry analysis were used to investigate the effects of casticin on proliferation, migration, invasion, and apoptosis of osteosarcoma cells in vitro. The intracellular Fe2+, ROS, MDA, GSH/GSSG content changes were detected using the corresponding assay kits. The mRNA sequencing + bioinformatics analysis and western blot were used to detect the possible mechanism. We found that casticin caused G2/M phase cell cycle arrest in human osteosarcoma cells, inhibited the migration and invasion, and induced cell apoptosis and ferroptosis. Mechanistic studies showed the ferroptosis pathway was enriched stronger than apoptosis. Casticin up-regulated the expression of HMOX1, LC3 and NCOA4, meanwhile it activated MAPK signaling pathways. Animal experiments proved that casticin also inhibited the growth and metastasis of osteosarcoma cell xenograft tumor in vivo. In conclusion, casticin can induce ferroptosis in osteosarcoma cells through Fe2+ overload and ROS production mediated by HMOX1 and LC3-NCOA4. This provides a new strategy for osteosarcoma treatment.
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Ferroptosis , Hemo-Oxigenasa 1 , Osteosarcoma , Especies Reactivas de Oxígeno , Animales , Humanos , Masculino , Ratones , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Línea Celular Tumoral , Ferroptosis/efectos de los fármacos , Ferroptosis/fisiología , Flavonoides/farmacología , Hemo-Oxigenasa 1/metabolismo , Hemo-Oxigenasa 1/genética , Hierro/metabolismo , Ratones Endogámicos BALB C , Ratones Desnudos , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/metabolismo , Osteosarcoma/patología , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Bladder cancer (BC) is the most common malignant tumor in urinary system. Although chemotherapy is one of the most important adjuvant treatments for BC, drug resistance, non-specific toxicity and severe side effects are the major obstacles to BC chemotherapy. Natural products have always been a leading resource of antitumor drug discovery, with the advantages of excellent effectiveness, low toxicity, multi-targeting potency and easy availability. In this study, we evaluated the potential anti-tumor effect of securinine (SEC), a natural alkaloid from Securinega suffruticosa, on BC cells in vitro and in vivo, and delineated the underlying mechanism. We found that SEC inhibited the proliferation, migration and invasion, induced the apoptosis of BC cells in vitro, and retarded the xenograft tumor growth of BC cell in vivo. Notably, SEC had a promising safety profile because it presented no or low toxicity on normal cells and mice. Mechanistically, SEC inactivated Wnt/ß-catenin signaling pathway while activated p38 and JNK signaling pathway. Moreover, ß-catenin overexpression, the p38 inhibitor SB203580 and the JNK inhibitor SP600125 both mitigated the inhibitory effect of SEC on BC cells. Furthermore, we demonstrated a synergistic inhibitory effect of SEC and gemcitabine (GEM) on BC cells in vitro and in vivo. Taken together, our findings suggest that SEC may exert anti-BC cell effect at least through the activation of p38 and JNK signaling pathways, and the inhibition of Wnt/ß-catenin signaling pathway. More meaningfully, the findings indicate that GEM-induced BC cell killing can be enhanced by combining with SEC.
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Antineoplásicos , Azepinas , Compuestos Heterocíclicos de Anillo en Puente , Lactonas , Piperidinas , Neoplasias de la Vejiga Urinaria , Humanos , Animales , Ratones , Vía de Señalización Wnt , Sistema de Señalización de MAP Quinasas , Proliferación Celular , Antineoplásicos/farmacología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Línea Celular Tumoral , beta Catenina/metabolismo , Movimiento Celular , ApoptosisRESUMEN
Subcellular mitochondria serve as sensors for energy metabolism and redox balance, and the dynamic regulation of functional and dysfunctional mitochondria plays a crucial role in determining cells' fate. Selective removal of dysfunctional mitochondria at the subcellular level can provide chondrocytes with energy to prevent degeneration, thereby treating osteoarthritis. Herein, to achieve an ideal subcellular therapy, cartilage affinity peptide (WYRGRL)-decorated liposomes loaded with mitophagy activator (urolithin A) were integrated into hyaluronic acid methacrylate hydrogel microspheres through microfluidic technology, named HM@WY-Lip/UA, that could efficiently target chondrocytes and selectively remove subcellular dysfunctional mitochondria. As a result, this system demonstrated an advantage in mitochondria function restoration, reactive oxygen species scavenging, cell survival rescue, and chondrocyte homeostasis maintenance through increasing mitophagy. In a rat post-traumatic osteoarthritis model, the intra-articular injection of HM@WY-Lip/UA ameliorated cartilage matrix degradation, osteophyte formation, and subchondral bone sclerosis at 8 weeks. Overall, this study indicated that HM@WY-Lip/UA provided a protective effect on cartilage degeneration in an efficacious and clinically relevant manner, and a mitochondrial-oriented strategy has great potential in the subcellular therapy of osteoarthritis.
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Objective: The purpose of this study was to investigate the association between serum polyunsaturated fatty acids (PUFAs) and bone mineral density (BMD). Methods: We performed a cross-sectional study based on data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. The weighted multiple linear regression model was utilized to determine the association between serum PUFAs and BMD. Further smoothed curve fitting and threshold effect analysis were conducted. Finally, we performed a subgroup analysis. Results: In total, 1979 participants aged 20-59 years were enrolled. After adjusting for all covariates, we found that serum docosapentaenoic acid (DPA) was positively associated with head BMD (ß = 0.0015, 95% Cl: 0.0004, 0.0026, P = 0.008296) and lumbar spine BMD (ß = 0.0005, 95% Cl: 0.0000, 0.0010, P = 0.036093), and serum eicosadienoic acid (EDA) was negatively associated with thoracic spine BMD (ß = -0.0008, 95% Cl: -0.0016, -0.0000, P = 0.045355). Smoothed curve fitting revealed a nonlinear positive association between serum DPA and lumbar spine BMD. Threshold effect analysis indicated that the threshold of serum DPA was 81.4 µmol/L. Subgroup analysis revealed a positive correlation between serum DPA and head BMD in the subgroup aged 50-59 years (ß = 0.0025, 95% Cl: 0.0002, 0.0049, P = 0.035249) and females (ß = 0.0026, 95% Cl: 0.0008, 0.0044, P = 0.005005). There was a positive relationship between serum DPA and lumbar spine BMD in females (ß = 0.0008, 95% Cl: 0.0001, 0.0015, P = 0.017900) and a negative association between serum EDA and thoracic spine BMD in the subgroup aged 30-39 years (ß = -0.0016, 95% Cl: -0.0031, -0.0001, P = 0.041331), males (ß = -0.0012, 95% Cl: -0.0023, -0.0001, P = 0.039364) and other races (ß = -0.0021, 95% Cl: -0.0037, -0.0006, P = 0.008059). Conclusion: This study demonstrated a linear positive relationship between serum DPA and head BMD, a nonlinear positive association between serum DPA and lumbar spine BMD, and a linear negative correlation between serum EDA and thoracic spine BMD in US adults.
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Densidad Ósea , Ácidos Grasos Insaturados , Masculino , Femenino , Humanos , Adulto , Encuestas Nutricionales , Absorciometría de Fotón , Estudios Transversales , Vértebras Lumbares/diagnóstico por imagenRESUMEN
Objectives: A new method was introduced using a smartphone's integrated inclinometer for rapid measurement of sagittal cervical parameters. The present study aims to compare the validity and reliability of the proposed method.Methods: We retrospectively reviewed 120 patients with cervical spondylosis treated at our hospital. The C0-2 Cobb angle, C2-7 Cobb angle, T1-slope (T1S), and neck tilt (NT) were selected as representative sagittal angles for this study. Two methods, the smartphone's integrated inclinometer and picture archiving and communication system (PACS), were used to measure these four representative angles. Validity, reliability, and measurement times were recorded and compared.Results: The representative parameters (C0-2 Cobb angle, C2-7 Cobb angle, T1S, and NT), the ICC was 0.957 (0.939-0.970), 0.971 (0.958-0.979), 0.974 (0.963-0.982) and 0.949 (0.927-0.964) for validity respectively. For the aforementioned representative parameters, the ICC values were 0.972 (0.960-0.980), 0.979 (0.969-0.985), 0.972 (0.959-0.980), 0.942 (0.917-0.959) for intraobserver reliability respectively. For the representative parameters mentioned above, the ICC values were 0.947 (0.926-0.963), 0.964 (0.949-0.975), 0.956 (0.938-0.969), 0.916 (0.881-0.940) for interobserver reliability respectively. For the validity of the representative parameters mentioned above, the Bland-Altman plot displayed a mean difference of 0.2, 0.1, 0.1, and 0.4°with a 95% CI of 4.3, 4.5, 3.4, and 4.1°, respectively. The measurement by smartphone's integrated inclinometer (46.31 ± 3.99 s) was significantly quicker than that by PACS (69.48 ± 3.25 s) according to independent-samples T test (p < 0.001).Conclusion: This novel smartphone measurement based on the integrated inclinometer is accurate and reliable for measuring cervical sagittal parameters rapidly and conveniently.
Sagittal parameters of the cervical spine have been widely applied in many types of spinal disorders for disease diagnosis, assessment, classification, treatment choice, and follow-up, so accurate, rapid, and convenient measurement of cervical sagittal parameters is important.Traditional measurement of sagittal parameters of the cervical spine have their own disadvantages.This novel smartphone measurement based on the integrated inclinometer is accurate and reliable for measuring cervical sagittal parameters rapidly and conveniently.
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Vértebras Cervicales , Teléfono Inteligente , Humanos , Reproducibilidad de los Resultados , Estudios Retrospectivos , CuelloRESUMEN
Ewing sarcoma (ES) is the second most common malignant bone tumor in children and has a poor prognosis due to early metastasis and easy recurrence. Necroptosis is a newly discovered cell death method, and its critical role in tumor immunity and therapy has attracted widespread attention. Thus, the emergence of necroptosis may provide bright prospects for the treatment of ES and deserves our further study. Here, based on the random forest algorithm, we identified 6 key necroptosis-related genes (NRGs) and used them to construct an NRG signature with excellent predictive performance. Subsequent analysis showed that NRGs were closely associated with ES tumor immunity, and the signature was also good at predicting immunotherapy and chemotherapy response. Next, a comprehensive analysis of key genes showed that RIPK1, JAK1, and CHMP7 were potential therapeutic targets. The Cancer Dependency Map (DepMap) results showed that CHMP7 is associated with ES cell growth, and the Gene Set Cancer Analysis (GSCALite) results revealed that the JAK1 mutation frequency was the highest. The expression of 3 genes was all negatively correlated with methylation and positively with copy number variation (CNV). Finally, an accurate nomogram was constructed with this signature and clinical traits. In short, this study constructed an accurate prognostic signature and identified 3 novel therapeutic targets against ES.
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A substantial amount of evidence suggests a close relationship between osteoporosis (OP) and Type 2 Diabetes Mellitus (T2DM), but the mechanisms involved remain unknown. Therefore, we conducted this study with the aim of screening for hub genes common to both diseases and conducting a preliminary exploration of common regulatory mechanisms. In the present study, we first screened genes significantly associated with OP and T2DM by the univariate logistic regression algorithm. And then, based on cross-analysis and random forest algorithm, we obtained three hub genes (ACAA2, GATAD2A, and VPS35) and validated the critical roles and predictive performance of the three genes in both diseases by differential expression analysis, receiver operating characteristic (ROC) curves, and genome wide association study (GWAS) analysis. Finally, based on gene set enrichment analysis (GSEA) and the construction of the miRNA-mRNA regulatory network, we conducted a preliminary exploration of the co-regulatory mechanisms of three hub genes in two diseases. In conclusion, this study provides promising biomarkers for predicting and treating both diseases and offers novel directions for exploring the common regulatory mechanisms of both diseases.
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Diabetes Mellitus Tipo 2 , MicroARNs , Osteoporosis , Humanos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/genética , Estudio de Asociación del Genoma Completo , Aprendizaje Automático , Osteoporosis/genética , MicroARNs/genética , Perfilación de la Expresión Génica , Biología ComputacionalRESUMEN
BACKGROUND: Osteosarcoma is a highly invasive and early metastatic tumor. At present, the toxic and side effects of chemotherapy affect the quality of life of cancer patients to varying degrees. Genipin is an extract of the natural medicine gardenia with various pharmacological activities. OBJECTIVE: The purpose of this study was to investigate the effect of Genipin on osteosarcoma and its potential mechanism of action. METHODS: Crystal violet staining, MTT assay and colony formation assay were used to detect the effect of genipin on the proliferation of osteosarcoma. The effects of vitexin on migration and invasion of osteosarcoma were detected by scratch healing assay and transwell assay. Hoechst staining and flow cytometry were used to detect the effect of genipin on apoptosis of osteosarcoma cells. The expression of related proteins was detected by Western blot. An orthotopic tumorigenic animal model was used to verify the effect of genipin on osteosarcoma in vivo. RESULTS: The results of crystal violet staining, MTT method and colony formation method proved that genipin significantly inhibited the proliferation of osteosarcoma cells. The results of the scratch healing assay and transwell assay showed that gen significantly inhibited the migration and invasion of osteosarcoma cells. The results of Hoechst staining and flow cytometry showed that genipin significantly promoted the apoptosis of osteosarcoma cells. The results of animal experiments show that genipin has the same anti-tumor effect in vivo. Genipin may inhibit the growth of osteosarcoma through PI3K/AKT signaling. CONCLUSION: Genipin can inhibit the growth of human osteosarcoma cells, and its mechanism may be related to the regulation of PI3K/AKT signaling pathway.
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Neoplasias Óseas , Iridoides , Osteosarcoma , Animales , Humanos , Apoptosis , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Óseas/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Osteosarcoma/tratamiento farmacológico , Osteosarcoma/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Calidad de Vida , Transducción de Señal , Iridoides/farmacologíaRESUMEN
[This corrects the article DOI: 10.1016/j.gendis.2020.07.014.].
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Osteosarcoma (OS) is a highly aggressive malignant bone tumor that mainly occurs in adolescents. At present, chemotherapy is the most commonly used method in clinical practice to treat OS. However, due to drug resistance, toxicity and long-term side effects, chemotherapy can't always provide sufficient benefits for OS patients, especially those with metastasis and recurrence. Natural products have long been an excellent source of anti-tumor drug development. In the current study, we evaluated the anti-OS activity of Echinatin (Ecn), a natural active component from the roots and rhizomes of licorice, and explored the possible mechanism. We found that Ecn inhibited the proliferation of human OS cells and blocked cell cycle at S phase. In addition, Ecn suppressed the migration and invasion, while induced the apoptosis of human OS cells. However, Ecn had less cytotoxicity against normal cells. Moreover, Ecn inhibited the xenograft tumor growth of OS cells in vivo. Mechanistically, Ecn inactivated Wnt/ß-catenin signaling pathway while activated p38 signaling pathway. ß-catenin over-expression and the p38 inhibitor SB203580 both attenuated the inhibitory effect of Ecn on OS cells. Notably, we demonstrated that Ecn exhibited synergistic inhibitory effect with cisplatin (DDP) on OS cells in vitro and in vivo. Therefore, our results suggest that Ecn may exert anti-OS effects at least partly through regulating Wnt/ß-catenin and p38 signaling pathways. Most meaningfully, the results obtained suggest a potential strategy to improve the DDP-induced tumor-killing effect on OS cells by combining with Ecn.
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Neoplasias Óseas , Osteosarcoma , Adolescente , Humanos , beta Catenina/metabolismo , Proliferación Celular , Osteosarcoma/metabolismo , Vía de Señalización Wnt , Apoptosis , Neoplasias Óseas/metabolismo , Línea Celular Tumoral , Movimiento CelularRESUMEN
Osteosarcoma (OS) is a primary malignant tumor of bone. Chemotherapy is one of the crucial approaches to prevent its metastasis and improve prognosis. Despite continuous improvements in the clinical treatment of OS, tumor resistance and metastasis remain dominant clinical challenges. Macropinocytosis, a form of non-selective nutrient endocytosis, has received increasing attention as a novel target for cancer therapy, yet its role in OS cells remains obscure. Benzethonium chloride (BZN) is an FDA-approved antiseptic and bactericide with broad-spectrum anticancer effects. Here, we described that BZN suppressed the proliferation, migration, and invasion of OS cells in vitro and in vivo, but simultaneously promoted the massive accumulation of cytoplasmic vacuoles as well. Mechanistically, BZN repressed the ERK1/2 signaling pathway, and the ERK1/2 activator partially neutralized the inhibitory effect of BZN on OS cells. Subsequently, we demonstrated that vacuoles originated from macropinocytosis and indicated that OS cells might employ macropinocytosis as a compensatory survival mechanism in response to BZN. Remarkably, macropinocytosis inhibitors enhanced the anti-OS effect of BZN in vitro and in vivo. In conclusion, our results suggest that BZN may inhibit OS cells by repressing the ERK1/2 signaling pathway and propose a potential strategy to enhance the BZN-induced inhibitory effect by suppressing macropinocytosis.
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Background: The periosteum plays a crucial role in the development and injury healing process of bone. The purpose of this study was to construct a biomimetic periosteum with a double cell sheet for bone tissue regeneration. Methods: In vitro, the human amniotic mesenchymal stem cells (hAMSCs) sheet was first fabricated by adding 50 âµg/ml ascorbic acid to the cell sheet induction medium. Characterization of the hAMSCs sheet was tested by general observation, microscopic observation, live/dead staining, scanning electron microscopy (SEM) and hematoxylin and eosin (HE) staining. Afterwards, the osteogenic cell sheet and vascular cell sheet were constructed and evaluated by general observation, alkaline phosphatase (ALP) staining, Alizarin Red S staining, SEM, live/dead staining and CD31 immunofluorescent staining for characterization. Then, we prepared the double cell sheet. In vivo, rat calvarial defect model was introduced to verify the regeneration of bone defects treated by different methods. Calvarial defects (diameter: 4 âmm) were created of Sprague-Dawley rats. The rats were randomly divided into 4 groups: the control group, the osteogenic cell sheet group, the vascular cell sheet group and the double cell sheet group. Macroscopic, micro-CT and histological evaluations of the regenerated bone were performed to assess the treatment results at 8 weeks and 12 weeks after surgery. Results: In vitro, hAMSCs sheet was successfully prepared. The hAMSCs sheet consisted of a large number of live hAMSCs and abundant extracellular matrix (ECM) that secreted by hAMSCs, as evidenced by macroscopic/microscopic observation, live/dead staining, SEM and HE staining. Besides, the osteogenic cell sheet and the vascular cell sheet were successfully prepared, which were verified by general observation, ALP staining, Alizarin Red S staining, SEM and CD31 immunofluorescent staining. In vivo, the macroscopic observation and micro-CT results both demonstrated that the double cell sheet group had better effect on bone regeneration than other groups. In addition, histological assessments indicated that large amounts of new bone had formed in the calvarial defects and more mature collagen in the double cell sheet group. Conclusion: The double cell sheet could promote to repair calvarial defects of rats and accelerate bone regeneration. The translational potential of this article: We successfully constructed a biomimetic cell-sheet-engineered periosteum with a double cell sheet by a simple, low-cost and effective method. This biomimetic periosteum may be a promising therapeutic strategy for the treatment of bone defects, which may be used in clinic in the future.
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INTRODUCTION: This study used systematic review and meta-analysis to evaluate the association between Helicobacter pylori infection and osteoporosis. MATERIALS AND METHODS: PubMed, Ovid and Web of Science were searched to include observational studies published in English comparing bone mineral density changes between Helicobacter pylori-positive and -negative participants. The quality of the included literature was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). R software was used for meta-analysis, and odds ratio (OR) and 95% confidence interval (CI) were calculated to evaluate the relationship between Helicobacter pylori infection and osteoporosis. RESULTS: Twenty-two studies involving 24,176 participants were included in the study. Our meta-analysis showed that Helicobacter pylori infection was significantly associated with the risk of osteoporosis (OR: 1.12, 95%CI: 1.03, 1.22). Participants infected with the CagA-positive Helicobacter pylori strain were more likely to develop osteoporosis (OR = 1.42, 95%CI: 1.09; 1.85). CONCLUSION: Infection with Helicobacter pylori, particularly the CagA-positive strain, has been associated with an increased risk of osteoporosis. The bone health of Helicobacter pylori-positive patients deserves more attention.
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Infecciones por Helicobacter , Helicobacter pylori , Osteoporosis , Humanos , Infecciones por Helicobacter/complicaciones , Osteoporosis/complicaciones , Densidad Ósea , Oportunidad RelativaRESUMEN
STUDY DESIGN: Retrospective Cohort Study. OBJECTIVES: To explore whether classification of the increased signal intensity (ISI) on magnetic resonance imaging (MRI) correlates with clinical presentations and outcomes in symptomatic thoracic ossification of ligamentum flavum (T-OLF) patients. METHODS: All patients with symptomatic T-OLF who underwent laminectomy at four institutions were reviewed. The ISI on preoperative T2-weighted MRI was divided into 3 groups, Grade 0, none; Grade 1, light (obscure); and Grade 2, intense (bright). Neurological function before surgery and at follow-up was evaluated by the revised Japanese Orthopedic Association (JOA) score. Patients' demographics, clinical manifestations, and surgical outcomes were compared. RESULTS: A total of 94 patients were involved. Preoperative MRI showed 32 patients in Grade 0, 39 patients in Grade 1, and 23 patients in Grade 2. Low extremities numbness, weakness, and clinical signs were less frequent in Grade 0 patients. The grade of ISI was correlated with the duration of symptoms and cord compression. Grade 0 patients had a better preoperative JOA score than those with ISI changes, while Grade 2 patients showed worse neurological recovery, longer duration of operation, more intraoperative blood loss, and a higher incidence of perioperative complications. CONCLUSION: The classification of ISI is an effective parameter for preoperatively assessing cord compression, clinical severity, and surgical outcomes in T-OLF patients. Grade 0 patients have relatively mild neurological impairment but are more likely to be misdiagnosed. Grade 2 indicates the worst clinical impairment and neurological recovery, and implies a risky and challenging surgery.
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Bone morphogenetic protein 9 (BMP9), also named as growth differentiation factor 2 (GDF-2), is the strongest cytokine that promotes osteogenic differentiation in the BMP family, and has broad clinical application value. Nevertheless, the mechanism of BMP9 promotes osteogenic differentiation remain unclear. TAZ, a transcriptional co-activator, has great effects on cell proliferation, differentiation, and stem cell self-renewal. In this research, we investigated the effects of TAZ in BMP9-induced osteogenic differentiation of mesenchymal stem cell line C3H10T1/2 (MSCs) and murine multi-lineage cell lines C2C12 and MEFs (MMCs) and explored its possible mechanisms. This study has found that BMP9 induces the expression of TAZ and promotes its nuclear translocation. Meanwhile, our study found that Ad-TAZ and TM-25659, a TAZ agonist, can enhance the osteogenic differentiation of MSCs and MMCs induced by BMP9. Conversely, Ad-si-TAZ and verteporfin, an inhibitor of TAZ, have the contradictory effect. Likewise, the promotion of TAZ to the BMP9-induced ectopic bone formation in vivo was confirmed by the subcutaneous transplantation of MSCs in nude mice. Furthermore, we have detected that TAZ might increase the levels of the phosphorylation of Smad1/5/8, p38, ERK1/2, and JNK induced by BMP9. Additionally, we also found that TAZ increased the total protein level of ß-catenin induced by BMP9. In summary, our results strongly indicated that TAZ will promote the osteogenic differentiation in MSCs and MMCs induced by BMP9 through multiple signal pathways.
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Background: With the arrival of the era of the aging population, the amount of joint arthroplasty surgery keeps rising, and the articles related to the application of tranexamic acid (TXA) in joint arthroplasty (we called the application of tranexamic acid in joint arthroplasty as TIA in this study) also show a blowout growth. Therefore, we conducted a bibliometric analysis of TIA-related publications to identify the main research trends and hot spots in this field in the last 20 years. Methods: In this study, publications in the field of TIA from January 1, 2002 to December 31, 2021 were searched in the Web of Science Core Collection (WoSCC). A total of 1,013 publications were evaluated for specific characteristics with Microsoft Excel software, CiteSpace, VOSviewer, and Online Analysis Platform of Literature Metrology (http://bibliometric.com/). Results: A total of 1,013 TIA-related articles were included in this study, and the number of articles in this field has increased yearly over the past 20 years. The USA and China dominated in the field of TIA. The Sichuan University published the most TIA-related articles among all the institutions. Of all the authors, Professor Pei was the most productive author with 64 articles. The lack of international cooperation was a significant problem in this field during the past 20 years. Furthermore, the results of the co-citation analysis and citation bursts analysis revealed that the safety and effectiveness of TIA and the optimal use strategy were the main trends and hotspots for the current and future. Conclusion: This bibliometric study reviewed the evolution trend of TIA research, and identified the countries, institutions, authors and journals that have made significant contributions to this field in the past 20 years, as well as the limitations and deficiencies in this field. In addition, this study revealed that the effectiveness and safety of TIA and the optimal use strategy was the current or future research trend and hotspot in this field.