RESUMEN
OBJECTIVE: This study aimed to distinguish tuberculous spondylodiscitis (TS) from pyogenic spondylodiscitis (PS) based on laboratory, magnetic resonance imaging (MRI) and computed tomography (CT) findings. Further, a novel diagnostic model for differential diagnosis was developed. METHODS: We obtained MRI, CT and laboratory data from TS and PS patients. Predictive models were built using binary logistic regression analysis. The receiver operating characteristic curve was analyzed. Both internal and external validation was performed. RESULTS: A total of 81 patients with PS (n = 46) or TS (n = 35) were enrolled. All patients had etiological evidence from the focal lesion. Disc signal or height preservation, skip lesion or multi segment (involved segments ≥ 3) involvement, paravertebral calcification, massive sequestra formation, subligamentous bone destruction, bone erosion with osteosclerotic margin, higher White Blood Cell Count (WBC) and positive result of tuberculosis infection T cell spot test (T-SPOT.TB) were more prevalent in the TS group. A diagnostic model was developed and included four predictors: WBC<7.265 * (10^9/L), skip lesion or involved segments ≥ 3, massive sequestra formation and subligamentous bone destruction. The model showed good sensitivity, specificity, and total accuracy (91.4%, 95.7%, and 93.8%, respectively); the area under the receiver operating characteristic curve (AUC) was 0.981, similar to the results of internal validation using bootstrap resampling (1000 replicates) and external validation set, indicating good clinical predictive ability. CONCLUSIONS: This study develop a good diagnostic model based on both CT and MRI, as well as laboratory findings, which may help clinicians distinguish between TS and PS.
RESUMEN
The aim of this study was to evaluate the influence factors of metagenomic next-generation sequencing (mNGS) negative results in the diagnosed patients with spinal infection. mNGS test was applied in a cohort of 114 patients with suspected spinal infection, among which 56 patients had a final diagnosis of spinal infection. mNGS achieved a sensitivity of 75.0% (95% CI, 61.6% to 85.6%) and a specificity of 84.5% (95% CI, 72.6% to 92.7%), using histopathology and culture results as reference. Diagnosed patients with a negative culture result had lower white blood cell account, percentage of neutrophilic granulocyte, C-reactive protein (all P<0.05) and relatively higher rate of prior antimicrobial treatment history (P=0.059). However, diagnosed patients with a negative mNGS result did not have such difference with mNGS-positive patients, suggesting that mNGS was not strictly limited by the above indicators, which presented the advantages of this technique from another point of view.
Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , Metagenómica , Sensibilidad y Especificidad , Humanos , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Masculino , Femenino , Metagenómica/métodos , Persona de Mediana Edad , Anciano , Adulto , Anciano de 80 o más Años , Adulto Joven , Enfermedades de la Columna Vertebral/microbiología , Enfermedades de la Columna Vertebral/diagnósticoRESUMEN
The bone matrix has distinct architecture and biochemistry which present a barrier to synthesizing bone-mimetic regenerative scaffolds. To mimic the natural structures and components of bone, biomimetic structural decellularized extracellular matrix (ECM)/regenerated silk fibroin (RSF) scaffolds incorporated with magnetic nanoparticles (MNP) are prepared using a facile synthetic methodology. The ECM/RSF/MNP scaffold is a hierarchically organized and interconnected porous structure with silk fibroin twined on the collagen nanofibers. The scaffold demonstrates saturation magnetization due to the presence of MNP, along with good cytocompatibility. Moreover, the ß-sheet crystalline domain of RSF and the chelated MNP could mimic the deposition of hydroxyapatite and enhance compressive modulus of the scaffold by ≈20%. The results indicate that an external static magnetic field (SMF) with a magnetic responsive scaffold effectively promotes cell migration, osteogenic differentiation, neogenesis of endotheliocytes in vitro, and new bone formation in a critical-size femur defect rat model. RNA sequencing reveals that the molecular mechanisms underlying this osteogenic effect involve calsequestrin-2-mediated Ca2+ release from the endoplasmic reticulum to activate Ca2+ /calmodulin/calmodulin-dependent kinase II signaling axis. Collectively, bionic magnetic scaffolds with SMF stimulation provide a potent strategy for bone regeneration through internal structural cues, biochemical composition, and external physical stimulation on intracellular Ca2+ homeostasis.
Asunto(s)
Fibroínas , Andamios del Tejido , Ratas , Animales , Andamios del Tejido/química , Fibroínas/química , Osteogénesis , Calcio , Biomimética , Calmodulina , Regeneración Ósea/fisiología , Fenómenos Magnéticos , Ingeniería de Tejidos/métodosRESUMEN
Spine surgeons should weigh the risks of anticoagulants against their benefits in preventing deep venous thrombosis (DVT), as they may increase the risk of bleeding. Spinal metastasis patients undergoing decompression with fixation are at a high risk for DVT, which may occur preoperatively. Therefore, anticoagulants should be administered preoperatively. This study aimed to evaluate the safety of the administration of anticoagulants in treating spinal metastasis patients with preoperative DVT. Therefore, we prospectively investigated the prevalence of DVT in these patients. Patients who were diagnosed with preoperative DVT were included in an anticoagulant group. Subcutaneous low-molecular-weight heparin (LMWH) was administered. Patients without DVT were included in a non-anticoagulant group. Data on patient information, clinical parameters, blood test results, and bleeding complications were also collected. Moreover, the safety of anticoagulants was analyzed. The prevalence of preoperative DVT was 8.0%. None of the patients developed pulmonary thromboembolism. Furthermore, no significant differences in blood loss, drainage volume, hemoglobin levels, number of transfusions, or preoperative trans-catheter arterial embolization were observed between the two groups. None of the patients developed major bleeding. However, two patients experienced wound hematoma and one experienced incisional bleeding in the non-anticoagulant group. Therefore, LMWH is safe for spinal metastasis patients. Future randomized controlled trials should be conducted to evaluate the validity of perioperative prophylactic anticoagulation therapy in these patients.
Asunto(s)
Neoplasias de la Columna Vertebral , Trombosis de la Vena , Humanos , Heparina de Bajo-Peso-Molecular/efectos adversos , Estudios Prospectivos , Neoplasias de la Columna Vertebral/complicaciones , Neoplasias de la Columna Vertebral/cirugía , Anticoagulantes/efectos adversos , Hemorragia/inducido químicamente , Trombosis de la Vena/epidemiología , Trombosis de la Vena/tratamiento farmacológico , Heparina/uso terapéuticoRESUMEN
Chondrocyte senescence is a decisive component of age-related osteoarthritis, however, the function of small noncoding RNAs (sncRNAs) in chondrocyte senescence remains underexplored. Human hip joint cartilage chondrocytes were cultivated up to passage 4 to induce senescence. RNA samples were extracted and then analyzed using small RNA sequencing and qPCR. ß-galactosidase staining was used to detect the effect of sncRNA on chondrocyte aging. Results of small RNA sequencing showed that 279 miRNAs, 136 snoRNAs, 30 snRNAs, 102 piRNAs, and 5 rasiRNAs were differentially expressed in senescent chondrocytes. The differential expression of 150 sncRNAs was further validated by qPCR. Transfection of sncRNAs and ß-galactosidase staining were also performed to further revealed that hsa-miR-135b-5p, SNORA80B-201, and RNU5E-1-201 have the function to restrain chondrocyte senescence, while has-piR-019102 has the function to promote chondrocyte senescence. Our data suggest that sncRNAs have therapeutic potential as novel epigenetic targets in age-related osteoarthritis.
Asunto(s)
MicroARNs , Osteoartritis , ARN Pequeño no Traducido , Humanos , Condrocitos/metabolismo , Osteoartritis/genética , MicroARNs/genética , MicroARNs/metabolismo , ARN Pequeño no Traducido/metabolismo , beta-Galactosidasa/genética , beta-Galactosidasa/metabolismo , Epigénesis Genética , Senescencia CelularRESUMEN
Oxidative stress can lead to nucleus pulposus cell (NPC) apoptosis, which is considered to be one of the main contributors to intervertebral disc degeneration (IVDD). Procyanidin B2 is a natural antioxidant that protects against oxidative stress. However, whether procyanidin B2 protects NPCs from oxidative stress remains unknown. In this study, we demonstrated that procyanidin B2 could reduce tert-butyl hydroperoxide-induced reactive oxygen species in rat NPCs and attenuate rat NPC apoptosis. Further experiments revealed that procyanidin B2 upregulated the expression of both nuclear factor erythroid 2-related factor 2 (Nrf2) and phosphorylation of protein kinase B (Akt). We then used silencing of Nrf2 and LY294002 to silence Nrf2 expression and block the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, respectively, and found that the protective roles of procyanidin B2 in NPCs were inhibited. Therefore, we demonstrated that procyanidin B2 alleviated rat NPC apoptosis induced by oxidative stress by upregulating Nrf2 via activation of the PI3K/Akt signaling pathway. This study provides a potential therapeutic approach for procyanidin B2 in IVDD, which might help in the development of new drugs for IVDD treatment.
Asunto(s)
Degeneración del Disco Intervertebral , Núcleo Pulposo , Ratas , Animales , Proteínas Proto-Oncogénicas c-akt/fisiología , Fosfatidilinositol 3-Quinasa/metabolismo , Fosfatidilinositol 3-Quinasa/uso terapéutico , Fosfatidilinositol 3-Quinasas , Núcleo Pulposo/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/uso terapéutico , Estrés Oxidativo , Degeneración del Disco Intervertebral/tratamiento farmacológico , Degeneración del Disco Intervertebral/metabolismo , ApoptosisRESUMEN
To provide a basis for promising exosome-based therapies against intervertebral disc degeneration (IDD), our present research aimed to identify a mechanism underlying the vesicle release from nucleus pulposus cells (NPCs). Scutellarin (SC) is a natural chemotherapeutic agent isolated from Erigeron breviscapus with a variety of biological activities. Here, we observed the significantly elevated autophagy levels in rat NPCs under the stimulation of SC, leading to a concomitant enhancement of intracellular vesicle release, which could be attributed to the inactivation of the phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/protein kinase B (Akt) pathway. To ensure that exosome release was driven by SC via the autophagic pathway, we implemented gain-of-function and loss-of-function studies by additionally using insulin-like growth factor-1 (IGF-1) and small-interfering RNA of autophagy-related gene 5 (ATG5), and the exosome secretion decreased in the case of attenuated autophagy. Evidently, the treatment with SC exerted the remarkable upregulation of Rab8a through the overexpression of ATG5. After the respective knockdown of ATG5 and Rab8a, the increased release of exosomes induced by SC was reversed, whereas the number of intracellular vesicles was restored. Overall, it can be concluded that SC contributes to the autophagy activation in NPCs by acting on the PI3K/PTEN/Akt pathway, which upregulates the expression of Rab8a and promotes the release of exosomes, inspiring novel therapeutic strategies in preventing IDD that might be fruitfully investigated.
Asunto(s)
Exosomas , Degeneración del Disco Intervertebral , Núcleo Pulposo , Animales , Apigenina , Apoptosis/genética , Autofagia/genética , Proteína 5 Relacionada con la Autofagia/metabolismo , Exosomas/metabolismo , Glucuronatos , Degeneración del Disco Intervertebral/tratamiento farmacológico , Degeneración del Disco Intervertebral/metabolismo , Núcleo Pulposo/metabolismo , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , RatasRESUMEN
OBJECTIVE: re is paucity in the literature on the epidemiological evidence of pulmonary thromboembolism (PE) and deep venous thrombosis (DVT) in spinal metastatic tumor patients. The aim of our study was to identify the incidence and risk factors for VTE in spinal metastasis patients treated with decompression with internal instruments. METHODS: We prospectively investigated the occurrence of VTE after decompression with internal fixations in 80 spinal metastasis patients. DVT was diagnosed by using a duplex ultrasonographical. PE was diagnosed by multidetector computed tomographic (CT) pulmonary angiography. Patient information and clinical parameters were collected. Risk factors were analyzed by comparing the difference between VTE and non-VTE cases. RESULTS: The incidence of developing a DVT was 6.3% (5/80). No patient suffered PE. In univariate analysis, the mean length of hospital stay after surgery until discharge for VTE group was longer than non-VTE group, ODI scores and AIS in VTE group were significantly worse than non-VTE group, D-dimer one-day postoperatively for VTE group was significantly higher than non-VTE group. In logistic regression, D-dimer at one-day postoperatively was the only risk factor. The areas under the ROC curves for the D-dimer (post) to distinguish between non-VTE and VTE was 0.971(P value=0.000). By means of the ROC analysis, the optimum thresholds of D-dimer(post) were determined to be 9.51â¯mg/L. The sensitivity and specificity for the optimum threshold were 100.0% and 92.0%. CONCLUSION: The prospective study of 80 patients with spinal metastasis who underwent decompression with internal fixation revealed an incidence of DVT of 6.3%, patients with increasingly D-dimer level at one-day postoperatively had a higher risk of DVT, and the optimum thresholds of D-dimer(post) were determined to be 9.51â¯mg/L.
Asunto(s)
Embolia Pulmonar , Neoplasias de la Columna Vertebral , Tromboembolia Venosa , Descompresión/efectos adversos , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Incidencia , Prevalencia , Estudios Prospectivos , Embolia Pulmonar/epidemiología , Factores de Riesgo , Neoplasias de la Columna Vertebral/complicaciones , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiologíaRESUMEN
Night shift workers with disordered rhythmic mechanical loading are more prone to intervertebral disc degeneration (IDD). Our results showed that circadian rhythm (CR) was dampened in degenerated and aged NP cells. Long-term environmental CR disruption promoted IDD in rats. Excessive mechanical strain disrupted the CR and inhibited the expression of core clock proteins. The inhibitory effect of mechanical loading on the expression of extracellular matrix genes could be reversed by BMAL1 overexpression in NP cells. The Rho/ROCK pathway was demonstrated to mediate the effect of mechanical stimulation on CR. Prolonged mechanical loading for 12 months affected intrinsic CR genes and induced IDD in a model of upright posture in a normal environment. Unexpectedly, mechanical loading further accelerated the IDD in an Light-Dark (LD) cycle-disrupted environment. These results indicated that intrinsic CR disruption might be a mechanism involved in overloading-induced IDD and a potential drug target for night shift workers.
Asunto(s)
Ritmo Circadiano , Susceptibilidad a Enfermedades , Degeneración del Disco Intervertebral/etiología , Degeneración del Disco Intervertebral/metabolismo , Estrés Mecánico , Factores de Edad , Animales , Biomarcadores , Supervivencia Celular , Senescencia Celular , Relojes Circadianos/genética , Ritmo Circadiano/genética , Modelos Animales de Enfermedad , Matriz Extracelular/metabolismo , Degeneración del Disco Intervertebral/diagnóstico por imagen , Degeneración del Disco Intervertebral/patología , Imagen por Resonancia Magnética , Masculino , Radiografía , Ratas , Resistencia a la TracciónRESUMEN
BACKGROUND: Exosomes may contain excess cellular components released by cells in response to harmful external stimuli to maintain cellular homeostasis. Inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), can induce cell apoptosis, alter cellular component expression levels, and stimulate exosome release. In this study, we examined whether exosomes released from nucleus pulposus cells (NPCs) under inflammatory conditions could induce normal NP cell apoptosis in rats and its underlining mechanism. METHODS: Exosomes were isolated from TNF-α-treated NPCs and used to treat normal NPCs. The effects were assessed by flow cytometry and western blot analysis. Anti-apoptotic insulin-like growth factor-1 (IGF-1) expression in NPCs was assessed by western blot analysis. Given the exosomal miRNAs might be the key factors of exosomes, bioinformatics approaches and quantitative real-time polymerase chain reaction (qRT-PCR) were used to identify IGF-1-regulating micro RNAs (miRNAs), including miR-16. Luciferase reporter assay assessed miR-16 regulation of IGF-1 and IGF-1 receptor (IGF-1R). NPCs were transfected with miR-16 mimic, and exosomes were applied to normal NPCs. NPCs were pretreated with 10 ng/mL TNF-α, transfected with miR-16 inhibitors, and the exosomes were isolated. Cell and exosome miR-16 levels were detected by qRT-PCR. Western blot analysis determined IGF-1, IGF-1R, and apoptotic marker levels in exosome-treated NPCs. RESULTS: Exosomes from TNF-α-treated NPCs induced apoptosis in normal NPCs and repressed IGF-1 expression. Exosomal miR-16 regulated IGF-1 and induced NPC apoptosis. The dual-luciferase reporter assay revealed that miR-16 binds the 3' untranslated regions (3'-UTRs) of IGF-1 and IGF-1R. Exosomal miR-16 repressed IGF-1 and the IGF-1R/phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway which therefore induced NPC apoptosis. Rescue experiments using miR-16 inhibitors further validated these findings. CONCLUSIONS: The inflammatory factor TNF-α stimulated exosome release from NPCs, which induced the apoptosis of normal NPCs through the actions of exosomal miR-16. Exosomal miR-16 directly repressed the anti-apoptotic IGF-1/IGF-1R pathway, increasing the apoptosis of NPCs.
RESUMEN
Although autophagy may be beneficial for maintaining the metabolic balance of the extracellular matrix (ECM) in the nucleus pulposus (NP) and its vitality under inflammation, the underlying mechanism still remains unclear. A previous study found that autophagy activation stimulated the release of exosomes in normal chondrocytes, which are located in a similar avascular environment and share many common features with those of nucleus pulposus cells (NPCs). This study explored the protective effect on matrix degradation in the NP by exosomes derived from autophagy-activated NPCs and exosomal microRNAs. NPCs-derived exosomes (NPCs-Exos) were isolated from culture medium of either normal NPCs or rapamycin-treated NPCs and quantified by nanoparticle tracking analysis. The effect of rapamycin-treated NPC-derived exosomes on NPCs were assessed by coculture with interleukin 1ß (IL-1ß)-stimulated NPCs. After examination of six major proteinases of the ECM, matrix metalloproteinase 13 (MMP-13) was chosen for further study. miR-27a, which targets MMP-13, was investigated through previous studies and bioinformatics tool. The levels of miR-27a were upregulated in both rapamycin-treated NPCs and their exosomes, compared to the control. When exosomal miR-27a was transferred into NPCs, it alleviated IL-1ß-induced degradation of the NPC ECM by targeting MMP-13. Autophagy activation may promote the release of NPCs-derived exosomes and thereby prevent the NPC matrix from degradation. Autophagy activation also alleviates intervertebral disc degeneration (IDD), at least partly via exosomal miR-27a, which restrains MMP-13 expression under IL-1ß stimulation. Our work elucidates a new mechanism for how autophagy may participate in preventing IDD, which may be a promising therapeutic strategy.
Asunto(s)
Degeneración del Disco Intervertebral , MicroARNs , Núcleo Pulposo , Autofagia , Células Cultivadas , Matriz Extracelular/metabolismo , Humanos , Degeneración del Disco Intervertebral/metabolismo , Metaloproteinasa 13 de la Matriz/metabolismo , MicroARNs/metabolismo , Núcleo Pulposo/metabolismo , Sirolimus/farmacologíaRESUMEN
Decorin (Dcn) is a member of the class I small leucine-rich proteoglycans, whose expression in the nucleus pulposus (NP) of intervertebral discs (IVDs) has been shown to increase with aging in humans and sheep. Dcn induces autophagy in endothelial cells; however, its precise role in NP and IVD degeneration during aging is not well understood. We addressed this question in the present study by treating rat nucleus pulposus cells (NPCs) with different concentrations of Dcn. The Western blot analysis and terminal deoxynucleotidyl transferase dUTP nick end labeling assay results showed that Dcn treatment induced autophagy and decreased apoptosis caused by interleukin (IL)-1ß application. This effect was dependent on the protein kinase B/mechanistic target of rapamycin (mTOR)/p70 S6 kinase signaling. Dcn treatment also decreased the expression of matrix metalloproteinase-3 and -13 and decreased the IL-1ß-induced attenuation of collagen type II and aggrecan levels. The role of Dcn in stimulating autophagy was further supported by the fact that the observed effects were abrogated by knocking down autophagy-related protein 7 with Atg7 small interfering RNA. Thus, Dcn protects NPCs in IVDs from IL-1ß-induced apoptosis and degeneration by promoting autophagy through mTOR signaling.
Asunto(s)
Degeneración del Disco Intervertebral , Núcleo Pulposo , Animales , Apoptosis , Autofagia/fisiología , Decorina , Células Endoteliales , Degeneración del Disco Intervertebral/metabolismo , Núcleo Pulposo/metabolismo , Ratas , Ovinos , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Our present study investigated whether exosome secretion of nucleus pulposus cells (NPCs) is regulated by autophagy. Different autophagic states of NPCs were induced by rapamycin (Rap), bafilomycin A1 (Baf) and other agents, and it was found that exosomes were secreted in an autophagy-dependent manner. Activation or inhibition of autophagy increased or decreased, respectively, the amount of exosomes that were released into the extracellular space. In addition, in order to confirm that Rap-promoted release of exosomes was mediated by autophagy rather than other pathways, we used autophagy associated gene 5 (ATG5) small-interfering RNA (siRNA) to silence the expression of ATG5 gene, which is indispensable for autophagy. The results showed that siRNA against ATG5 (siATG5) induced an accumulation of intraluminal vesicles (ILVs) in NPCs and a concomitant decrease in the amount of exosomes isolated from supernatant. Ras homolog gene (Rho) and Rho-associated coiled-coil forming protein kinase (ROCK) family molecules are capable of cytoskeletal remodeling and affecting vesicle transport. Therefore, we carried out targeted interventions and evaluated the effects of the RhoC/ROCK2 pathway on the secretion of exosomes within autophagic environment. Knockdown of RhoC and ROCK2 with corresponding siRNA significantly inhibited the secretion of exosomes originating from ILVs in NPCs, even when NPCs were subsequently treated with Rap. Taken together, our findings suggest that autophagy positively regulates expression levels of RhoC and ROCK2, and that the RhoC/ROCK2 pathway exerts a key function on NPCs-derived exosome secretion.
Asunto(s)
Autofagia/fisiología , Exosomas/metabolismo , Núcleo Pulposo/metabolismo , Proteína rhoC de Unión a GTP/genética , Animales , Secreciones Corporales/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Ratas Sprague-Dawley , Quinasas Asociadas a rho/metabolismo , Proteína rhoC de Unión a GTP/metabolismoRESUMEN
Objective To study the gene expression of cardiac mesenchymal cells in patients with type 2 diabetes mellitus (T2DM)based on a whole-genome high-throughput sequencing dataset,screen differentially expressed genes,analyze the genetics signature of cardiac mesenchymal cells in T2DM patients by bioinformatics analysis,and explore the environmental chemicals related to the key differentially expressed genes. Methods The dataset GSE106177 was obtained from Gene Expression Omnibus (GEO) database.The dataset was pre-processed and analyzed by Network Analyst,Cytoscape 3.7.1,String11.0,CTD,and HMDD for screening for differentially expressed genes,enrichment analysis,establishment of protein-protein interaction (PPI) networks,and screening for relevant environmental chemicals. Results The gene expression pattern of cardiac mesenchymal cells in T2DM patients was significantly different from that in the control group.There were 135 differentially expressed genes,of which 58 (42.96%) were up-regulated and 77 (57.04%) were down-regulated.The differentially expressed genes mainly participated in biological processes such as multicellular organism development,anatomical structure development,and system development and were mainly involved in hepatocellular carcinoma,Cushing's syndrome,and cholesterol metabolism.PPI network showed that UBC was the core protein node.The microRNA-Gene interaction network showed that seven microRNAs,represented by hsa-mir-8485,interacted with the differentially expressed genes.Key T2DM related genes such as UBC,DNER,and CNTN1 interacted with bisphenol A. Conclusions The gene expression profile of cardiac mesenchymal cells markedly changes in T2DM patients,during which UBC may play an important biological role.Bisphenol A exposure may also affect the development and normal function of cardiac cells in T2DM patients.
Asunto(s)
Diabetes Mellitus Tipo 2/metabolismo , Células Madre Mesenquimatosas/metabolismo , MicroARNs/genética , Miocardio/citología , Transcriptoma , Biología Computacional , Perfilación de la Expresión Génica , HumanosRESUMEN
BACKGROUND The incidence and prognostic factors of chondrosarcoma patients have been reported in early studies. However, the association between risk factors and the incidence or prognosis of chondrosarcoma patients with pulmonary metastasis remains unclear. Therefore, we assessed these risk factors among chondrosarcoma patients with pulmonary metastasis. MATERIAL AND METHODS From 1365 chondrosarcoma patients in the Surveillance, Epidemiology, and End Results (SEER) database, we collected the information of 69 patients with pulmonary metastasis at the initial diagnosis of chondrosarcoma from 2010 to 2016. We investigated the incidence, risk factors, and prognostic factors for pulmonary metastasis patients by using multivariate logistic regression and multivariate Cox regression analyses. RESULTS Data from a total of 69 (6.8%) chondrosarcoma patients with pulmonary metastasis at initial diagnosis were extracted. Patients with the following characteristics were positively associated with higher risk of pulmonary metastasis: dedifferentiated subtype, high grade of malignancy, extracompartmental tumor (Enneking B), presence of regional lymph nodes, local recurrence, large tumor size (larger than 15 cm), and being married. Older patients (older than 67 years), and patients with clear cell chondrosarcoma or large tumor size (larger than 15 cm) exhibited the worse prognosis and survival (overall and cancer-specific). Resection of the primary tumor tended to be correlated with a better prognosis. CONCLUSIONS The incidence of pulmonary metastasis in chondrosarcoma was approximately 6.8%, with poor prognosis. Identifying risk factors and their associations with the incidence and prognosis in chondrosarcoma patients with pulmonary metastasis could provide a reference for clinical surveillance and guide the design of personalized treatment plans.
Asunto(s)
Condrosarcoma/diagnóstico , Condrosarcoma/epidemiología , Neoplasias Pulmonares/epidemiología , Neoplasias Pulmonares/secundario , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Incidencia , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Modelos de Riesgos Proporcionales , Factores de Riesgo , Análisis de Supervivencia , Adulto JovenRESUMEN
HCC stem cells were reported as posttreatment residual tumor cells that play a pivotal role in tumor relapse. Fusing dendritic cells (DCs) with tumor cells represents an ideal approach to effectively activate the antitumor immunity in vivo. DC/HCC stem cell vaccine provides a potential strategy to generate polyclonal immune response to multiple tumor stem cell antigens including those yet to be unidentified. To assess the potential capacity of DC/HCC stem cell vaccines against HCC, CD90+HepG2 cells were sorted from the HCC cell line HepG2. DC and CD90+HepG2 and DC and HepG2 fused cells were induced by polyethylene glycol (PEG). The influence of fusion cells on proliferation and immunological function transformation of lymphocytes was assessed by FCM and ELISA assay, respectively. The cytotoxicity assay of specific fusion cell-induced CTLs against HepG2 was conducted by CytoTox 96 Non-Radioactive Cytotoxicity Assay kit in vitro. At last, the prevention of HCC formation in vivo was described in a mouse model. The results of FCM analysis showed that the proportion of CD90+HepG2 cells in the spheral CD90+HepG2 enriched by suspension sphere culture was ranging from 98.7% to 99.5%, and 57.1% CD90+HepG2/DC fused cells were successfully constructed. The fusion cells expressed a higher level of costimulatory molecules CD80, CD83, CD86, and MHC-I and MHC-II molecules HLA-ABC and HLA-DR than did immature DCs (P < 0.05). And the functional analysis of fusion cell-induced CTLs also illustrated that CD90+HepG2/DC fusion cells showed a greater capacity to activate proliferation of lymphocytes in vitro (P < 0.05). The CD90+HepG2/DC-activated CTLs had a specific killing ability against CD90+HepG2 cells in vivo. These results suggested that CD90+HepG2/DC fusion cells could efficiently stimulate T lymphocytes to generate specific CTLs targeting CD90+HepG2 cells. It might be a promising strategy of immunotherapy for HCC.
RESUMEN
OBJECTIVE: A retrospective study was designed to evaluate the effectiveness of CT-guided core needle biopsy in diagnosing spinal lesions through comparison with C-arm guidance. METHODS: From April 2013 to July 2017, a total of 188 patients, who suffered from spinal lesions or had malignant tumor history with a new spinal fracture, were included in this study. There were 96 men and 92 women, with an average of 57.1 years. A total of 238 core needle biopsies were performed. A total of 140 core needle biopsies were carried out under C-arm guidance in 102 patients (group 1); 98 core needle biopsies were carried out under CT guidance in 86 patients (group 2); 108 core needle biopsies were performed in thoracic vertebrae, 116 were in lumbar vertebrae, and 14 were in sacral vertebrae. Seventy-eight patients accepted surgical treatment after biopsies. For these patients, the histological pathologies of the biopsy and surgery were compared to evaluate the accuracy of the biopsy. For the other 110 patients who did not receive surgical treatment, the treatment response and the clinical course were used to evaluate the accuracy of the biopsy. The success rate, the diagnostic accuracy rate, the true positive/negative rate, and complications of the two groups were calculated and compared. RESULTS: There were no significant differences in sex, age, and lesion sites between the C-arm guidance group (group 1) and the CT guidance group (group 2). There were no complications in the two groups. Pathological diagnoses were established in 232 of 238 biopsies. They revealed that 52 were primary malignant tumors, 12 were benign tumors, 70 were metastatic tumors, 4 were tuberculosis, and 94 were classified as "other." The success rate of group 2 was higher than that of group 1, but it was not statistically significant (95.7% vs 100%; P = 0.098). According to the final diagnosis, the diagnostic accuracy rates were calculated and compared. There was no significant difference between the two groups (95.5% vs 96.9%; P = 0.835). The kappa coefficient was used to analyze the concordance between the histological pathologies of the biopsy and the final diagnosis in the two groups. The kappa values of the two group were 0.909 and 0.939, respectively. The results showed good consistency in both groups, but seemed better for group 2. CONCLUSION: CT-guided core needle biopsy is a relatively safe and effective procedure for diagnosing spinal lesions with a high diagnostic accuracy rate and few complications.
Asunto(s)
Biopsia con Aguja Gruesa/métodos , Enfermedades de la Columna Vertebral/diagnóstico por imagen , Enfermedades de la Columna Vertebral/patología , Adulto , Anciano , Anciano de 80 o más Años , Biopsia con Aguja Gruesa/efectos adversos , Diagnóstico Diferencial , Errores Diagnósticos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Radiografía Intervencional/métodos , Estudios Retrospectivos , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Neoplasias de la Columna Vertebral/patología , Neoplasias de la Columna Vertebral/secundario , Tomografía Computarizada por Rayos X/métodos , Adulto JovenRESUMEN
STUDY DESIGN: A prospective study. OBJECTIVE: The aim of this study was to evaluate the outcomes and efficacy of using a 10Fr elastic tube with a regular negative pressure ball to treat the operative pleural tear in the complicated single-stage posterior approach thoracic spine surgeries. SUMMARY OF BACKGROUND DATA: In some complicated single-stage posterior approach thoracic spine surgeries, such as total en bloc spondylectomy, pleural tear is quite inevitable. Traditional chest tube with a water-sealed bottle has many shortcomings, as pain, inconvenience, and other complications. In many thoracic surgeries, a smaller-caliber elastic tube has been used to avoid such complications and achieve quick recovery. However, there are concerns about the efficacy and safety of the smaller-caliber elastic tube. METHODS: A prospective trial was performed in 72 patients between April 2008 and March 2012. Pleural tear occurred in 19 patients, among whom 10 patients were inserted a 10Fr elastic tube with a regular negative pressure ball (Group I), and nine were inserted a 28Fr chest tube with a water-sealed bottle (Group II). Comparative evaluation of the clinical and radiographic data was carried out. RESULTS: The basic condition of two groups did not differ significantly. The oxygen saturation monitor, hospital length of stay, average volume, and failure rate of drainage between two groups were not statistically significant. The difference of the visual analog score was significant (1.10â±â0.35 vs. 3.89â±â0.59, Pâ<â0.001). CONCLUSION: Patients who received a 10Fr elastic tube with a regular negative pressure ball experienced less pain and a tendency of quicker recovery than those who received a 28Fr chest tube with a water-sealed bottle. The complication rate in Group I was not higher than Group II, indicating an equally good drainage efficacy. LEVEL OF EVIDENCE: 2.
Asunto(s)
Tubos Torácicos , Drenaje/instrumentación , Complicaciones Intraoperatorias/cirugía , Pleura/lesiones , Vértebras Torácicas/cirugía , Adulto , Anciano , Drenaje/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
Lung cancer invading the spine was previously considered unresectable and fatal and, consequently, there are few reports focusing on tumors located in the lower lung lobe and invading the spine. With the development of spinal instrumentation and surgical techniques, and wider acceptance of spondylectomy by surgeons, radical surgical resection has become feasible. Here, we present a case of a male patient with a left lower lung cancer invading thoracic vertebrae who underwent complete resection with sagittal en bloc hemivertebrectomy with video-assisted thoracoscopy. A 60-year-old man complained of left chest pain for 3 months. Chest computed tomography and thoracic vertebrae magnetic resonance image revealed that a tumor in the left lower lung lobe had invaded the seventh and eighth thoracic vertebrae and the eighth rib. As no lymph node or distant metastasis was detected by positron emission tomography-computed tomography, the patient was diagnosed with left lower lung cancer directly invading the seventh and eighth thoracic vertebrae and the eighth rib (T4N0M0, stage IIIA) instead of metastasizing to the thoracic vertebrae. An en bloc resection of the lung tumor and the involved vertebrae was performed by a thoracic surgeon and orthopaedic surgeon with video-assisted thoracoscopy. Six months after the operation, there was no evidence of local recurrence, and the patient had recovered well. En Bloc resection with video-assisted thoracoscopy for lung cancer invading thoracic vertebrae is a safe and feasible surgical method. This method can significantly improve the safety and convenience of this type of surgery.