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The Waveflex semi-rigid-dynamic-internal-fixation system shows good short-term effects in the treatment of lumbar degenerative diseases, but there are few long-term follow-up studies, especially for recovery of sagittal balance. Fifty patients with lumbar degenerative diseases treated from January 2016 to October 2017 were retrospectively analysed: 25 patients treated with Waveflex semi-rigid-dynamic-internal-fixation system (Waveflex group) and 25 patients treated with double-segment PLIF (PLIF group). Clinical efficacy was evaluated by Visual Analogue Scale (VAS) and Oswestry Disability Index (ODI). Imaging data before surgery and at 3 months, 1 year, and 5 years postoperatively was used for imaging indicator assessment. Local disc degeneration of the cephalic adjacent segment (including disc height index (DHI), intervertebral foramen height (IFH), and range of motion (ROM)) and overall spinal motor function (including lumbar lordosis (LL), pelvic incidence (PI), sacral slope (SS), pelvic tilt (PT), and |PI-LL|) were analysed. Regarding clinical efficacy, comparison of VAS and ODI scores between the Waveflex and PLIF groups showed no significant preoperative or postoperative differences. The comparison of the objective imaging indicators showed no significant differences in the DHI, IFH, LL, |PI-LL|, and SS values between the Waveflex and PLIF groups preoperatively and 3 months postoperatively (P > 0.05). These values were significantly different at 1 and 5 years postoperatively (P < 0.05), and the Waveflex group showed better ROM values than those of the PLIF group (P < 0.05). PI values were not significantly different between the groups, but PT showed a significant improvement in the Waveflex group 5 years postoperatively (P < 0.05). The Waveflex semi-rigid dynamic fixation system can effectively reduce the probability of intervertebral disc degeneration in upper adjacent segments. Simultaneously, patients in the Waveflex group showed postoperative improvements in LL, spinal sagittal imbalance, and quality of life.
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Degeneración del Disco Intervertebral , Vértebras Lumbares , Humanos , Masculino , Femenino , Degeneración del Disco Intervertebral/cirugía , Degeneración del Disco Intervertebral/diagnóstico por imagen , Persona de Mediana Edad , Estudios Retrospectivos , Vértebras Lumbares/cirugía , Vértebras Lumbares/diagnóstico por imagen , Resultado del Tratamiento , Adulto , Rango del Movimiento Articular , Fusión Vertebral/métodos , Anciano , Fijadores Internos , Lordosis/diagnóstico por imagen , Lordosis/cirugíaRESUMEN
The self-assembled metal-organic cages (MOCs) have been evolved as a paradigm of enzyme-mimic catalysts since they are able to synergize multifunctionalities inherent in metal and organic components and constitute microenvironments characteristic of enzymatic spatial confinement and versatile host-guest interactions, thus facilitating unconventional organic transformations via unique driving-forces such as weak noncovalent binding and electron/energy transfer. Recently, MOC-based photoreactors emerged as a burgeoning platform of supramolecular photocatalysis, displaying anomalous reactivities and selectivities distinct from bulk solution. This perspective recaps two decades journey of the photoinduced radical reactions by using photoactive metal-organic cages (PMOCs) as artificial reactors, outlining how the cage-confined photocatalysis was evolved from stoichiometric photoreactions to photocatalytic turnover, from high-energy UV-irradiation to sustainable visible-light photoactivation, and from simple radical reactions to multi-level chemo- and stereoselectivities. We will focus on PMOCs that merge structural and functional biomimicry into a single-cage to behave as multi-role photoreactors, emphasizing their potentials in tackling current challenges in organic transformations through single-electron transfer (SET) or energy transfer (EnT) pathways in a simple, green while feasible manner.
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STUDY DESIGN: Multicenter retrospective observational study. OBJECTIVE: This study aimed to distinguish tuberculous spondylitis (TS) from pyogenic spondylitis (PS) using magnetic resonance imaging (MRI). Further, a novel diagnostic model for differential diagnosis was developed. SUMMARY OF BACKGROUND DATA: TS and PS are the two most common spinal infections. Distinguishing between these types clinically is challenging. Delayed diagnosis can lead to deficits or kyphosis. Currently, there is a lack of radiology-based diagnostic models for TS and PS. METHODS: We obtained radiologic images from MRI imaging of patients with TS and PS and applied the least absolute shrinkage and selection operator regression to select the optimal features for a predictive model. Predictive models were built using multiple logistic regression analysis. Clinical utility was determined using decision curve analysis, and internal validation was performed using bootstrap resampling. RESULTS: A total of 201 patients with TS (n=105) or PS (n=96) were enrolled. We identified significant differences in MRI features between both groups. We found that noncontiguous multivertebral and single-vertebral body involvement were common in TS and PS, respectively. Vertebral bone lesions were more severe in the TS group than in the PS group (Z=-4.553, P <0.001). The patients in the TS group were also more prone to vertebral intraosseous, epidural, and paraspinal abscesses ( P <0.001). A total of 8 predictors were included in the diagnostic model. Analysis of the calibration curve and area under the receiver operating characteristic curve suggested that the model was well-calibrated with high prediction accuracy. CONCLUSIONS: This is the largest study comparing MRI features in TS and PS and the first to develop an MRI-based nomogram, which may help clinicians distinguish between TS and PS.
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Espondilitis , Tuberculosis de la Columna Vertebral , Humanos , Tuberculosis de la Columna Vertebral/diagnóstico , Espondilitis/diagnóstico por imagen , Columna Vertebral/patología , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodosRESUMEN
BACKGROUND: Postmenopausal women face a heightened risk of developing new vertebral compression fractures (NVCFs) following percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCFs). This study aimed to develop and validate a visual nomogram model capable of accurately predicting NVCF occurrence post-PKP to optimize treatment strategies and minimize occurrence. METHODS: This retrospective study included postmenopausal women diagnosed with OVCF who underwent PKP at the Affiliated Hospital of Shandong University of Traditional Chinese Medicine between January 2016 and January 2021. Patient data, including basic information, surgical details, imaging records, and laboratory findings, were collected. The patients were categorized into two groups based on NVCF occurrence within 2 years post-PKP: the NVCF group and the non-NVCF group. Following the utilization of least absolute shrinkage and selection operator (LASSO) regression for feature selection, a nomogram was constructed. Model differentiation, calibration, and clinical applicability were evaluated using receiver operating characteristic (ROC), calibration, and decision (DCA) curve analyses. RESULTS: In total, 357 patients were included in the study. LASSO regression analysis indicated that cement leakage, poor cement diffusion, and endplate fracture were independent predictors of NVCF. The nomogram demonstrated excellent predictive accuracy and clinical applicability. CONCLUSIONS: This study used LASSO regression to identify three independent predictors of NVCF and developed a predictive model that could effectively predict NVCF occurrence in postmenopausal women. This simple prediction model can support medical decision-making and is feasible for clinical practice.
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Fracturas por Compresión , Cifoplastia , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Humanos , Femenino , Cifoplastia/efectos adversos , Cifoplastia/métodos , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/etiología , Fracturas de la Columna Vertebral/cirugía , Fracturas por Compresión/diagnóstico por imagen , Fracturas por Compresión/etiología , Fracturas por Compresión/cirugía , Estudios Retrospectivos , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas Osteoporóticas/etiología , Fracturas Osteoporóticas/cirugía , Posmenopausia , Nomogramas , Resultado del Tratamiento , Cementos para Huesos/uso terapéuticoRESUMEN
The present study used network pharmacology and molecular docking to predict the active ingredients and mechanisms of action of Astragalus radix (AR) to promote osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs), and cell experiments were conducted for verification. First, network pharmacology was used to predict the effective components, targets, and mechanisms of action of AR to promote osteogenic differentiation. The effective components and corresponding target proteins of AR, and the target proteins of osteogenic differentiation were collected through the database. The intersection targets of the two were used for the construction and analysis of a protein-protein interaction (PPI) network. Gene Oncology (GO) and Kyoto Encyclopedia of Genes, and Genomes (KEGG) enrichment analyses were conducted. Next, molecular docking technology was carried out to verify the interaction between the active ingredient and the target protein, and to select the appropriate effective active ingredient. Finally, the results of network pharmacology analysis were verified by in vitro experiments. A total of 95 potential targets were retrieved by searching the intersection of AR and osteogenic differentiation targets. PPI network analysis indicated that RAC-α-serine-threonine-protein kinase (Akt1) was considered to be the most reliable target for AR to regulate osteogenic differentiation. GO enrichment analysis included 21 biological processes, 21 cellular components and 100 molecular functions. KEGG enrichment analysis indicated that the class I phosphatidylinositol-3 kinase (PI3K)-serine-threonine kinase (Akt) signaling pathway may play an important role in promoting osteogenic differentiation. The results of molecular docking showed that quercetin's performance was improved compared with that of kaempferol. In vitro experiments showed that quercetin promoted the expression of osteogenic marker proteins (including collagen I, Runt-related transcription factor 2 and osteopontin) in BMSCs and activated the PI3K/Akt signaling pathway. AR acted on Akt1 targets through its main active component quercetin, and promoted the osteogenic differentiation of BM-MSCs by activating the PI3K/Akt signaling pathway.
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Medicamentos Herbarios Chinos , Proteínas Proto-Oncogénicas c-akt , Diferenciación Celular , Medicamentos Herbarios Chinos/farmacología , Simulación del Acoplamiento Molecular , Farmacología en Red , Osteogénesis , Fosfatidilinositol 3-Quinasas , Quercetina , Células Madre Mesenquimatosas/químicaRESUMEN
Background: The pathogenesis of ankylosing spondylitis (AS) is still not clear, and immune-related genes have not been systematically explored in AS. The purpose of this paper was to identify the potential early biomarkers most related to immunity in AS and develop a predictive disease risk model with bioinformatic methods and the Gene Expression Omnibus database (GEO) to improve diagnostic and therapeutic efficiency. Methods: To identify differentially expressed genes and create a gene coexpression network between AS and healthy samples, we downloaded the AS-related datasets GSE25101 and GSE73754 from the GEO database and employed weighted gene coexpression network analysis (WGCNA). We used the GSVA, GSEABase, limma, ggpubr, and reshape2 packages to score immune data and investigated the links between immune cells and immunological functions by using single-sample gene set enrichment analysis (ssGSEA). The value of the core gene set and constructed model for early AS diagnosis was investigated by using receiver operating characteristic (ROC) curve analysis. Results: Biological function and immune score analyses identified central genes related to immunity, key immune cells, key related pathways, gene modules, and the coexpression network in AS. Granulysin (GNLY), Granulysin (GZMK), CX3CR1, IL2RB, dysferlin (DYSF), and S100A12 may participate in AS development through NK cells, CD8+ T cells, Th1 cells, and other immune cells and represent potential biomarkers for the early diagnosis of AS occurrence and progression. Furthermore, the T cell coinhibitory pathway may be involved in AS pathogenesis. Conclusion: The AS disease risk model constructed based on immune-related genes can guide clinical diagnosis and treatment and may help in the development of personalized immunotherapy.
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Linfocitos T CD8-positivos , Espondilitis Anquilosante , Humanos , Espondilitis Anquilosante/genética , Biomarcadores , Biología Computacional , Bases de Datos FactualesRESUMEN
Objective: Recent studies have suggested that high levels of ß2-microglobulin are linked to cognitive deterioration; however, it is unclear how this connects to spinal cord injury (SCI). This study sought to determine whether there was any association between cognitive decline and serum ß2-microglobulin levels in patients with SCI. Methods: A total of 96 patients with SCI and 56 healthy volunteers were enrolled as study participants. At the time of enrollment, specific baseline data including age, gender, triglycerides (TG), low-density lipoprotein (LDL), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting blood glucose (FBG), smoking, and alcohol use were recorded. Each participant was assessed by a qualified physician using the Montreal cognitive assessment (MoCA) scale. Serum ß2-microglobulin levels were measured using an enzyme-linked immunosorbent assay (ELISA) reagent for ß2-microglobulin. Results: A total of 152 participants were enrolled, with 56 in the control group and 96 in the SCI group. There were no significant baseline data differences between the two groups (p > 0.05). The control group had a MoCA score of 27.4 ± 1.1 and the SCI group had a score of 24.3 ± 1.5, with the difference being significant (p < 0.05). The serum ELISA results revealed that the levels of ß2-microglobulin in the SCI group were considerably higher (p < 0.05) than those in the control group (2.08 ± 0.17 g/mL compared to 1.57 ± 0.11 g/mL). The serum ß2-microglobulin level was used to categorize the patients with SCI into four groups. As serum ß2-microglobulin levels increased, the MoCA score reduced (p < 0.05). After adjustment of baseline data, further regression analysis showed that serum ß2-microglobulin level remained an independent risk factor for post-SCI cognitive impairment. Conclusions: Patients with SCI had higher serum levels of ß2-microglobulin, which may be a biomarker for cognitive decline following SCI.
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Disfunción Cognitiva , Traumatismos de la Médula Espinal , Humanos , Microglobulina beta-2/análisis , Biomarcadores , Presión Sanguínea , Disfunción Cognitiva/diagnóstico , Traumatismos de la Médula Espinal/complicacionesRESUMEN
To study the mechanism of 25 ingredient decoction for setting a fracture (TDSF) in fracture treatment using network pharmacology. The TCMSP, BATMAN-TCM, HERB, and Uniprot protein databases were used to identify the active ingredients and targets of TDSF. Fracture-related targets were collected from the gene cards and the online mendelian inheritance in man databases. The acquisition of common genes of active compounds of TDSF and disease fractures was carried out using the Venny software. The Cytoscape 3.7.1 software and String database were used to construct a network diagram of drug-active ingredient-target-disease and the main core targets were obtained by protein interaction analysis. The Metascape platform was used to perform gene oncology functional and Kyoto encyclopedia of genes and genomes pathway enrichment analyses for common drug-disease targets. A total of 311 active ingredients and 348 targets were associated with TDSF, with 5197 targets related to fractures and 224 common targets between the 2 keywords. Key targets included serine/threonine protein kinase 1, tumor necrosis factor, interleukin 6, tumor protein 53, and vascular endothelial growth factor. Important roles of the following pathway were identified: cancer, lipid, and atherosclerosis; AGE-RAGE signaling pathway in diabetic complications; chemical carcinogenesis - receptor activation; PI3K -Akt signaling pathway; platinum drug resistance; cAMP signaling pathway; transcriptional mis regulation in cancer; serotonergic synapse; and malaria. TDSF mainly treats fractures by acting on multiple targets, such as serine/threonine protein kinase 1, tumor necrosis factor, interleukin 6, tumor protein 53, and vascular endothelial growth factor, and regulating the PI3K/AKT and cAMP signaling pathways.
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Medicamentos Herbarios Chinos , Farmacología en Red , Humanos , Interleucina-6 , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Factor A de Crecimiento Endotelial Vascular , Quinasas Ciclina-Dependientes , Factor de Necrosis Tumoral alfa , Bases de Datos Genéticas , Treonina , Serina , Medicina Tradicional ChinaRESUMEN
Objective: To explore the influence and potential factors of the bone cement dispersion state on residual pain after vertebral augmentation. Methods: The cases included in this retrospective cohort study were patients treated with vertebral augmentation (VA) for osteoporotic vertebral compression fractures (OVCFs) between July 2018 and June 2021. According to the type of cement diffusion distribution, the patients were divided into a sufficient diffusion group (Group A) and an insufficient diffusion group (Group B). The differences in the baseline data, visual analog scale (VAS), Oswestry disability index score (ODI), injured vertebral height (IVH), and local kyphosis angle (LKA) between the two groups were analyzed. Assessments were performed preoperatively on the 2nd day postoperation and at the last follow-up. The imaging data of injured vertebrae were accurately reconstructed by a GE AW4.7 workstation, and the differences in the vertebral body volume, bone cement volume, and bone cement volume ratio were compared between the groups. Result: After screening, 36 patients were included. (1) The postoperative VAS and ODI scores of the two groups were significantly improved compared with the preoperative scores. (2) On the 2nd day postoperation and the last follow-up, the VAS and ODI scores of Group A were significantly different from those of Group B, and Group A outperformed Group B. (3) The IVH and LKA of the two groups were improved after the operation, and no significant difference was found between the groups. (4) Significant differences were found in the bone cement volume and bone cement volume ratio between the groups, and Group A was larger than Group B. Conclusions: Sufficient bone cement diffusion can reduce residual pain after vertebral augmentation.
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Fracturas por Compresión , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Vertebroplastia , Humanos , Cementos para Huesos/uso terapéutico , Fracturas por Compresión/diagnóstico por imagen , Fracturas por Compresión/cirugía , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas Osteoporóticas/cirugía , Columna Vertebral , DolorRESUMEN
OBJECTIVE: New vertebral compression fracture (NVCF) occurring after bone cement injection in middle-aged and elderly patients with vertebral compression fracture is very common. Preoperative baseline characteristics and surgical treatment parameters have been widely studied as a risk factor, but the importance of the patients' laboratory indicators has not been thoroughly explored. We aimed to explore the relationship between laboratory indicators and NVCF, and attempt to construct a clinical prediction model of NVCF together with other risk factors. METHODS: Retrospective analysis was performed for 200 patients who underwent bone cement injection (percutaneous kyphoplasty or vertebroplasty) for vertebral compression fractures between January 2019 and January 2020. We consulted the relevant literature and collated the factors affecting the occurrence of NVCF. Feature selection of patients with NVCF was optimized using the least absolute shrinkage and selection operator regression model, which was used to conduct multivariable logistic regression analysis, to create a predictive model incorporating the selected features. The discrimination, calibration, and clinical feasibility of the predictive model were assessed using the concordance index (C-index), calibration plots, and decision curve analysis. Internal validation was performed using Bootstrap resampling verification. RESULTS: Time from injury to surgery exceeding 7 days, low osteocalcin levels, elevated homocysteine levels, osteoporosis, mode of operation (percutaneous vertebroplasty), lack of postoperative anti-osteoporosis treatment, and poor diffusion of bone cement were independent risk factors for NVCF in middle-aged and elderly patients with vertebral compression fracture after bone cement injection. The C-index of the nomogram constructed using these seven factors was 0.895, indicating good discriminatory ability. The calibration plot showed that the model was well calibrated. Bootstrap resampling verification yielded a significant C-index of 0.866. Decision curve analysis demonstrated that the greatest clinical net benefit for predicting NVCF after bone cement injection could be achieved with a threshold of 1%-91%. CONCLUSION: This nomogram can effectively predict NVCF incidence after bone cement injection in middle-aged and elderly patients with vertebral compression fracture, thus aiding clinical decision-making and postoperative management, promoting effective postoperative rehabilitation, and improving the quality of life.
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Fracturas por Compresión , Cifoplastia , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Vertebroplastia , Anciano , Persona de Mediana Edad , Humanos , Fracturas por Compresión/cirugía , Fracturas de la Columna Vertebral/cirugía , Fracturas de la Columna Vertebral/etiología , Cementos para Huesos/efectos adversos , Fracturas Osteoporóticas/cirugía , Fracturas Osteoporóticas/etiología , Estudios Retrospectivos , Modelos Estadísticos , Nomogramas , Calidad de Vida , Resultado del Tratamiento , Pronóstico , Vertebroplastia/efectos adversos , Cifoplastia/efectos adversosRESUMEN
Intervertebral disc degeneration (IDD) is the leading cause of lower back pain, which is one of the primary factors that lead to disability and pose a serious economic burden. The key pathological processes involved are extracellular matrix degradation, autophagy, apoptosis, and inflammation of nucleus pulposus cells. Non-coding RNAs (ncRNAs), including microRNAs, long ncRNAs and circular RNAs, are key regulators of the aforementioned processes. ncRNAs are differentially expressed in tissues of the intervertebral disc between healthy individuals and patients and participate in the pathological progression of IDD via a complex pattern of gene regulation. However, the regulatory mechanisms of ncRNAs in IDD remain unclear. The present review summarizes the latest insights into the regulatory role of ncRNAs in IDD and sheds light on potentially novel therapeutic strategies for IDD that may be implemented in the future.
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ETHNOPHARMACOLOGICAL RELEVANCE: Heidihuang Wan (HDHW) is a classic Chinese herbal formula, which was first recorded in the "Suwen Bingji Qiyi Baoming Collection" written by Liu Wansu during the Jin Dynasty (1115-1234 AD). It is commonly used clinically for the treatment of kidney diseases and its curative effect is stable. Previous animal experiments have confirmed that HDHW can effectively improve renal fibrosis. However, the underlying pharmacological mechanism remains unclear. AIMS OF THIS STUDY: Renal tubular epithelial cell (RTEC) apoptosis is one of the main pathological features of renal fibrosis. This study aimed to observe the effect and underlying mechanism of HDHW on the apoptosis of RTECs to further explore the pathological mechanism of HDHW against renal fibrosis. MATERIALS AND METHODS: We examined the HDHW composition in rat serum. In vitro, we first screened out the optimal intervention concentration of HDHW on RTECs using the MTT assay. Hypoxia/reoxygenation was then used to induce apoptosis of RTECs (H/R-RTECs), which were divided into H/R-RTEC, astragaloside IV (positive control), HDHW, and RTECs groups. After 48 h of drug intervention, apoptosis of RTECs was detected using flow cytometry and protein expression was detected by western blotting. The 5/6 nephrectomy rat model was constructed and divided into the normal control, 5/6 nephrectomy, HDHW, and astragaloside IV groups. After 8 weeks of treatment, TUNEL staining was used to detect cell apoptosis, and western blotting was used to detect protein expression. RESULTS: HDHW downregulated the expression of pro-apoptotic proteins Bax and Caspase3, up-regulated the expression of anti-apoptotic protein Bcl-2, activated the PI3K/Akt/mTOR signaling pathway, and reversed the early apoptosis of RTECs, thereby resisting the apoptosis of RTECs. CONCLUSION: HDHW inhibits apoptosis of RTECs by modulating the PI3K/Akt/mTOR signaling pathway. This study provides experimental evidence for the anti-fibrotic effect of HDHW on the kidneys and partially elucidates its pharmacological mechanism of action.
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Enfermedades Renales , Proteínas Proto-Oncogénicas c-akt , Ratas , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Apoptosis , Células Epiteliales , Proteínas Reguladoras de la Apoptosis/metabolismo , Enfermedades Renales/patología , FibrosisRESUMEN
PURPOSE: In this study, a large diameter visible trephine was designed and used in percutaneous endoscopic lumbar interbody fusion to increase endoscopic bone decompression efficiency. Large diameter visible trephine-related technical notes and preliminary clinical experience are described. METHODS: A large diameter visible trephine was designed with normal diameter visible trephine as template. A total of 38 patients with lumbar degenerative diseases who underwent single-level percutaneous endoscopic lumbar interbody fusion with large or normal diameter visible trephine were included into a retrospective study. Operation time, bone decompression time, blood loss, intraoperative fluoroscopy, bone decompression fluoroscopy, and dura or nerve injury cases were recorded and analyzed statistically. Visual Analog Scale (VAS) scores and Oswestry Disability Index (ODI) were used to analyze the clinical outcomes of the 2 groups. RESULTS: The baseline data of the 2 groups were statistically similar. There was no significant difference in postoperative VAS and ODI scores between the 2 groups. Operation time and bone decompression time of large diameter visible trephine group were significantly shorter than that of normal diameter visible trephine group (P < 0.05). Intraoperative fluoroscopy times and bone decompression fluoroscopy times of large diameter visible trephine group were significantly more than that of normal diameter visible trephine group (P < 0.05). Blood loss of the 2 groups were not statistically different. There were no dura or nerve injury cases in the 2 groups. CONCLUSIONS: For percutaneous endoscopic lumbar interbody fusion, the large diameter visible trephine is a safe and efficient endoscopic bone decompression tool under fluoroscopic guidance.
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Fusión Vertebral , Humanos , Resultado del Tratamiento , Estudios Retrospectivos , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/cirugía , Endoscopía , Procedimientos Quirúrgicos Mínimamente InvasivosRESUMEN
Astragaloside IV (AS IV) and tanshinone (TS IIA) are the main natural components of Salvia miltiorrhiza and Radix Astragali, respectively. The amalgam of TS IIA and AS IV has potential therapeutic value in many inflammation-related diseases. However, the aftereffect of TS IIA and AS IV for lumbar disc herniation is not clear. Although the function of miR-223 in the inflammation-related JAK/STAT pathway is unknown, it is particularly expressed in human degenerative nucleus pulposus cells. This study has investigated the efficacy of the combined application of TS IIA and AS IV in the treatment of intervertebral disc nucleus pulposus cells (NP cells) injured by lipopolysaccharide (LPS). After miR-223 inhibitor imitated NP cells, the state of the JAK family and STAT family was recognized by Western blotting (Western blot, WB) and reverse transcriptase quantitative polymerase chain reaction (qPCR). The shRNA lentivirus interference vector targeting the STAT family was constructed, and the NP cell line stably interfering with the STAT gene was established after transfection. The expression of TNF-α, IL-6, MMP-9, MMP-3, caspase-1, and caspase-3 was detected by lipopolysaccharide (WTNP cells), control virus NP cells, STAT downregulation NP cells, enzyme-linked immunosorbent assay (ELISA), Western blot, and qPCR, respectively. The cell survival rate was detected by flow cytometry and TUNEL staining reverse transcriptase-polymerase chain reaction (qPCR). NP cells were treated with TS IIA and AS IV which had been made into different concentrations, and then, the expression of miR-223, p-STAT1, and p-JAK families was detected by WB Western blotting and qPCR. MiR-223 selectively acts on JAK2/STAT1 pathway, increases the expression of TNF-α, IL-6, MMP-9, MMP-3, caspase3-1, and caspase-3, and induces apoptosis, which can be eliminated by silencing STAT1. TS IIA combined with AS IV could inhibit the expression of miR-223, p-STAT1, and p-JAK2 in NP cells, and they showed a dose-dependent tendency to p-STAT1 and p-JAK2. This study shows that miR-223 promotes the inflammatory response and induces cell injury of NP cells by acting on the JAK2/STAT1 pathway, and the combination of TS IIA and AS IV may protect NP cells by downregulating miR-223 and inhibiting the expression of JAK2 and STAT1.
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Abietanos/farmacología , Janus Quinasa 2/metabolismo , Núcleo Pulposo/efectos de los fármacos , Factor de Transcripción STAT1/metabolismo , Saponinas/farmacología , Triterpenos/farmacología , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Células Cultivadas , Regulación hacia Abajo/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Degeneración del Disco Intervertebral/patología , Janus Quinasa 2/genética , MicroARNs/metabolismo , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patología , Factor de Transcripción STAT1/genética , Transducción de Señal/efectos de los fármacosRESUMEN
We have developed a protocol for electrochemical decarboxylative C3 alkylation of a wide range of quinoxalin-2(1H)-ones under metal- and additive-free conditions. N-Hydroxyphthalimide esters derived from chain, cyclic, primary, secondary, and tertiary carboxylic acids with a broad scope proved to be suitable substrates. This operationally simple protocol performed in an undivided cell under constant-current conditions is suitable for late-stage functionalization of quinoxalin-2(1H)-ones. The reactions can even be carried out with a 3 V battery as a power source, which demonstrates that organic electrosynthesis can be accomplished without the need for specialized equipment.
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On the basis of the scaffolds widely used in drug design, a series of novel spirooxindole derivatives containing hydantoin, thiohydantoin, urea, and thiourea moieties have been designed, synthesized, characterized, and first evaluated for their biological activities. The diastereoselectivity mechanism is proposed, and the systematic conformational analysis is performed. The bioassay results show that the target compounds possess moderate to good antiviral activities against tobacco mosaic virus (TMV), among which compound 22 shows the highest antiviral activity in vitro as well as inactivation, curative, and protection activities in vivo (45 ± 1, 47 ± 3, 50 ± 1, and 51 ± 1%, 500 mg/L, respectively), higher than ribavirin (38 ± 1, 36 ± 1, 38 ± 1, and 36 ± 1%, 500 mg/L, respectively). Thus, compound 22 is a promising candidate for anti-TMV development. Most of these compounds show broad-spectrum fungicidal activities against 14 kinds of phytopathogenic fungi and selective fungicidal activities against Physalospora piricola, Sclerotinia sclerotiorum, and Rhizoctonia cerealis. Additionally, some of these compounds exhibit insecticidal activity against Culex pipiens pallens, Mythimna separata, Helicoverpa armigera, and Pyrausta nubilalis. Compound 17 exhibits the highest larvicidal activity (LC50 was 0.32 mg/L) against C. pipiens pallens.
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Antivirales/síntesis química , Antivirales/farmacología , Fungicidas Industriales/síntesis química , Fungicidas Industriales/farmacología , Insecticidas/síntesis química , Insecticidas/farmacología , Animales , Antivirales/química , Culex/efectos de los fármacos , Diseño de Fármacos , Hongos/efectos de los fármacos , Fungicidas Industriales/química , Hidantoínas/química , Insecticidas/química , Estructura Molecular , Mariposas Nocturnas/efectos de los fármacos , Relación Estructura-Actividad , Tiohidantoínas/química , Tiourea/química , Virus del Mosaico del Tabaco/efectos de los fármacos , Urea/químicaRESUMEN
BACKGROUND: As one of the endoplasmic reticulum proteins, calreticulin (CRT) plays a significant role in the body, and it has been used by many researchers as a target for anti-tumor therapy. OBJECTIVE: The main purpose of the present study was to study expression of CRT of human osteosarcoma, and analyze the distinctions between normal and tumor tissues, pre- and post-chemotherapy patients, and metastatic and non-metastatic tumors in respect to this expression. METHODS: Immunofluorescent staining was used in order to investigate expression of CRT in diverse tissues. The whole RNA and proteins were extracted from the crushed tissues and used in the reverse transcription polymerase chain reaction (RT-PCR) and western blotting analysis. RESULTS: The present study detected expression of CRT in patients with osteosarcoma and revealed a higher expression level in normal tissues surrounding tumors compared with tumor tissues, in the non-metastasis group compared with the metastasis group, and in the chemotherapy group compared with the non-chemotherapy group. CONCLUSIONS: These results could indicate a brand-new biological marker which may be applied to estimate the features and prognosis of osteosarcoma.
Asunto(s)
Biomarcadores de Tumor/genética , Calreticulina/genética , Osteosarcoma/genética , Pronóstico , Adolescente , Adulto , Niño , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Osteosarcoma/patologíaAsunto(s)
Neoplasias Óseas , Predisposición Genética a la Enfermedad , Osteosarcoma , Proteínas Proto-Oncogénicas c-mdm2 , Animales , Humanos , Neoplasias Óseas/genética , Osteosarcoma/genética , Proteínas Proto-Oncogénicas c-mdm2/genética , Revisiones Sistemáticas como Asunto , Metaanálisis como AsuntoRESUMEN
This study evaluated the accuracy of T1-weighted magnetic resonance imaging (MRI) in determining the osteotomy plane in 21 patients with osteosarcoma undergoing limb-salvage surgery. Twelve cases involved the distal femur and nine cases involved the proximal tibia. Mean patient age was 16.3 years (range, 12-24 years). None of the patients presented with evidence of metastasis. After being placed on neoadjuvant chemotherapy, all patients were treated with en bloc resection and a custom prosthesis. Intramedullary extension was measured on preoperative MRI and radiographs, and also on postoperative specimen by gross and histopathological evaluation. The osteotomy plane was confirmed at 30 mm distal from the primary tumor based on T1-weighted MRI. Mean intramedullary extension measured on MRI, radiographs, and gross examination were 107.4+/-34.5, 78.6+/-25.6, and 92.6+/-20.5 mm, respectively; actual mean extension was 104.3+/-32.8 mm. There were no significant differences between the actual extension and the extension measured on MRI according to statistical analysis. Intramedullary extension was measured accurately on MRI, which also confirmed the surgical margins. These findings indicate using 30 mm distal from the primary tumor as the osteotomy plane based on T1-weighted MRI is safe.