RESUMEN
BACKGROUND: Insular low-grade gliomas (LGGs) are surgically challenging due to their proximity to critical structures like the corticospinal tract (CST). PURPOSE: This study aims to determine if preoperative CST shape metrics correlate with postoperative motor complications in insular LGG patients. STUDY TYPE: Retrospective. POPULATION: 42 patients (mean age 40.26 ± 10.21 years, 25 male) with insular LGGs. FIELD STRENGTH/SEQUENCE: Imaging was performed using 3.0 Tesla MRI, incorporating T1-weighted magnetization-prepared rapid gradient-echo, T2-weighted space dark-fluid with spin echo (SE), and diffusional kurtosis imaging (DKI) with gradient echo sequences, all integrated with echo planar imaging. ASSESSMENT: Shape metrics of the CST, including span, irregularity, radius, and irregularity of end regions (RER and IER, respectively), were compared between the affected and healthy hemispheres. Total end region radius (TRER) was determined as the sum of RER 1 and RER 2. The relationships between shape metrics and postoperative short-term (4 weeks) and long-term (>8 weeks) motor disturbances assessing by British Medical Research Council grading system, was analyzed using multivariable regression models. STATISTICAL TESTING: Paired t-tests compared CST metrics between hemispheres. Logistic regression identified associations between these metrics and motor disturbances. The models were developed using all available data and there was no independent validation dataset. Significance was set at P < 0.05. RESULTS: Short-term motor disturbance risk was significantly related to TRER (OR = 199.57). Long-term risk significantly correlated with IER 1 (OR = 59.84), confirmed as a significant marker with an AUC of 0.78. Furthermore, the CST on the affected side significantly had the greater irregularity, larger TRER and RER 1, and smaller span compared to the healthy side. DATA CONCLUSION: Preoperative evaluation of TRER and IER 1 metrics in the CST may serve as a tool for assessing the risk of postoperative motor complications in insular LGG patients. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 2.
RESUMEN
OBJECTIVES: This study aims to explore the relationship between the methylation levels of the O-6-methylguanine-DNA methyltransferase (MGMT) promoter and the structural connectivity in insular gliomas across hemispheres. METHODS: We analyzed 32 left and 29 right insular glioma cases and 50 healthy controls, using differential tractography, correlational tractography, and graph theoretical analysis to investigate the correlation between structural connectivity and the methylation level. RESULTS: The differential tractography results revealed that in left insular glioma, the volume of affected inferior fronto-occipital fasciculus (IFOF, p = 0.019) significantly correlated with methylation levels. Correlational tractography results showed that the quantitative anisotropy (QA) value of peritumoral fiber tracts also exhibited a significant correlation with methylation levels (FDR < 0.05). On the other hand, in right insular glioma, anterior internal part of the reticular tract, IFOF, and thalamic radiation showed a significant correlation with methylation levels but at a different correlation direction from the left side (FDR < 0.05). The graph theoretical analysis showed that in the left insular gliomas, only the radius of graph was significantly lower in methylated MGMT group than unmethylated group (p = 0.047). No significant correlations between global properties and methylation levels were observed in insular gliomas on both sides. CONCLUSION: Our findings highlight a significant, hemisphere-specific correlation between MGMT promoter methylation and structural connectivity in insular gliomas. This study provides new insights into the genetic influence on glioma pathology, which could inform targeted therapeutic strategies.
Asunto(s)
Neoplasias Encefálicas , Glioma , Humanos , Metilación de ADN , Glioma/diagnóstico por imagen , Glioma/genética , Glioma/tratamiento farmacológico , Enzimas Reparadoras del ADN/genética , O(6)-Metilguanina-ADN Metiltransferasa/genética , Metilasas de Modificación del ADN/genética , Regiones Promotoras Genéticas , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patología , Proteínas Supresoras de Tumor/genéticaRESUMEN
Metastasis of colorectal cancer (CRC) is a leading cause of mortality among CRC patients. Elevated COX-2 and PD-L1 expression in colon cancer tissue has been linked to distant metastasis of tumor cells. Although COX-2 inhibitors and immune checkpoint inhibitors demonstrate improved anti-tumor efficacy, their toxicity and variable therapeutic effects in individual patients raise concerns. To address this challenge, it is vital to identify traditional Chinese medicine components that modulate COX-2 and PD-1/PD-L1: rosmarinic acid (RA) exerts striking inhibitory effect on COX-2, while ginsenoside Rg1 (GR) possesses the potential to suppress the binding of PD-1/PD-L1. In this study we investigated whether the combination of RA and GR could exert anti-metastatic effects against CRC. MC38 tumor xenograft mouse model with lung metastasis was established. The mice were administered RA (100 mg·kg-1·d-1, i.g.) alone or in combination with GR (100 mg·kg-1·d-1, i.p.). We showed that RA (50, 100, 150 µM) or a COX-2 inhibitor Celecoxib (1, 3, 9 µM) concentration-dependently inhibited the migration and invasion of MC38 cells in vitro. We further demonstrated that RA and Celecoxib inhibited the metastasis of MC38 tumors in vitro and in vivo via interfering with the COX-2-MYO10 signaling axis and inhibiting the generation of filopodia. In the MC38 tumor xenograft mice, RA administration significantly decreased the number of metastatic foci in the lungs detected by Micro CT scanning; RA in combination with GR that had inhibitory effect on the binding of PD-1 and PD-L1 further suppressed the lung metastasis of colon cancer. Compared to COX-2 inhibitors and immune checkpoint inhibitors, RA and GR displayed better safety profiles without disrupting the tissue structures of the liver, stomach and colon, offering insights into the lower toxic effects of clinical traditional Chinese medicine against tumors while retaining its efficacy.
Asunto(s)
Neoplasias del Colon , Neoplasias Pulmonares , Humanos , Animales , Ratones , Antígeno B7-H1/metabolismo , Ciclooxigenasa 2/metabolismo , Ácido Rosmarínico , Celecoxib/farmacología , Celecoxib/uso terapéutico , Inhibidores de la Ciclooxigenasa 2/farmacología , Inhibidores de la Ciclooxigenasa 2/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Receptor de Muerte Celular Programada 1/metabolismo , Línea Celular Tumoral , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/metabolismo , Neoplasias Pulmonares/tratamiento farmacológicoRESUMEN
This study aimed to explore the expression of long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) in patients with acute myocardial infarction (AMI) and its inflammatory regulation mechanism through miR-211/interleukin 10 (IL-10) axis.A total of 75 participants were enrolled in this study: 25 healthy people in the control group, 25 patients with stable angina pectoris (SAP) in the SAP group, and 25 patients with AMI in the AMI group. Real-time qPCR was used to detect mRNA expression levels of NEAT1, miR-211, and IL-10. The interaction between miR-211, NEAT1, and IL-10 was confirmed by dual-luciferase reporter assay, and protein expression was detected using western blot.High expression of NEAT1 in peripheral blood mononuclear cells (PBMCs) of patients with AMI was negatively related to serum creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), tumor necrosis factor-α (TNF-α), IL-6, and IL-1ß and was positively correlated with left ventricular ejection fraction (LVEF). In THP-1 cells, miR-211 was confirmed to target and inhibit IL-10 expression. NEAT1 knockdown and miR-211-mimic markedly decreased IL-10 protein levels, whereas anti-miR-211 markedly increased IL-10 protein levels. Importantly, miR-211 level was negatively related to NEAT1 and IL-10 levels, whereas IL-10 level was positively related to the level of NEAT1 expression in PBMCs of patients with AMI.LncRNA NEAT1 was highly expressed in PBMCs of patients with AMI, and NEAT1 suppressed inflammation via miR-211/IL-10 axis in PBMCs of patients with AMI.
Asunto(s)
Interleucina-10 , Leucocitos Mononucleares , MicroARNs , Infarto del Miocardio , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/sangre , MicroARNs/sangre , MicroARNs/genética , Interleucina-10/sangre , Interleucina-10/metabolismo , Infarto del Miocardio/sangre , Infarto del Miocardio/genética , Infarto del Miocardio/metabolismo , Leucocitos Mononucleares/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Anciano , Inflamación/genética , Inflamación/sangre , Inflamación/metabolismo , Estudios de Casos y ControlesRESUMEN
Interacting massive spin-1 fields have been widely used in cosmology and particle physics. We obtain a new condition on the validity of the classical limit of these theories related to the nontrivial constraints that exist for vector field components. A violation of this consistency condition causes a singularity in the time derivative of the auxiliary component and could impact, for example, the field's cosmic history and superradiance around black holes. We show that gauge-invariant interactions are generally safe from this problem, even though the mass term explicitly breaks the gauge symmetry. Such restrictions for interactions are expected to exist generically in many other nontrivially constrained systems.
RESUMEN
ABSTRACT: Bone morphogenetic protein 4 (BMP4) is a proinflammatory factor. The expression of BMP4 is reduced in the adipose and enhanced in the myocardium and vascular during obesity. It is possibly involved in the process of inflammatory response of the myocardium and vascular. Obesity, often regarded as a risk factor for cardiovascular diseases, is a kind of inflammatory response. This study aimed to investigate the relationship of BMP4 with obesity and cardiovascular disease. Ob/ob mice were used as the experimental group, and C57BL/6 mice were used as the control group. The two groups were further divided into 2 subgroups based on the mice carrying adenovirus-encoding shRNA for BMP4 or Lac Z genes. The messenger RNA and protein levels of BMP4, interleukin-1ß, and interleukin-9 were significantly higher in the myocardial tissue and aorta of ob/ob+ Lac Z shRNA than those in the other 3 groups, whereas the levels in the ob/ob+ BMP4 shRNA group were significantly decreased and comparable with those in the control groups. BMP4 is significantly upregulated in the myocardial tissue and aorta of obese mice, and this suggests that BMP4 is an risk factor involved in the local inflammatory response.
Asunto(s)
Inflamación , Obesidad , Animales , Proteína Morfogenética Ósea 4/genética , Proteína Morfogenética Ósea 4/metabolismo , Inflamación/genética , Inflamación/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Miocardio/metabolismo , Obesidad/genética , Obesidad/metabolismo , ARN Interferente PequeñoRESUMEN
Over the last decade, researchers have found abnormal expression of transient receptor potential (TRP) channels. In particular, members of the thermally sensitive subclass (thermo-TRPs) are involved in many disease processes. Moreover, they have a vital role in the occurrence and development of gastric cancer (GC). Accordingly, thermo-TRPs constitute a major pharmacological target, and the elucidation of the mechanisms underlying their response to physiological stimuli or drugs is key for notable advances in GC treatment. Therefore, this paper summarizes the existing literature about thermo-TRP protein expression changes that are linked to the incidence and progression of GC. The review also discusses the implication of such association to pathology and cell physiology and identifies potential thermo-TRP protein targets for diagnosis and treatment of GC.
Asunto(s)
Neoplasias Gástricas , Canales de Potencial de Receptor Transitorio , Humanos , Canales de Potencial de Receptor Transitorio/metabolismo , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genéticaRESUMEN
A fistula between the pulmonary artery (PA) and the left atrium (LA) is a rare congenital heart disease that usually presents with cyanosis, clubbing, and dyspnea, as well as the signs and symptoms of a right-to-left shunt. Herein, we report a 16-year-old girl with a fistula between the right PA and the LA. This type of fistula could lead to systemic desaturation. This patient also had an atrial septal defect of the secundum type and has been followed up without treatment. The clinical manifestations and treatment of fistulas located between the PA and LA are also reviewed in this report.
Asunto(s)
Fístula/diagnóstico por imagen , Atrios Cardíacos/anomalías , Defectos del Tabique Interatrial/diagnóstico por imagen , Arteria Pulmonar/anomalías , Adolescente , Cateterismo Cardíaco , Femenino , Fístula/congénito , HumanosRESUMEN
Double-chambered left ventricle (DCLV) is an extremely rare congenital heart disease. In this condition, the left ventricle is divided into two chambers by a septum or muscle fiber with abnormal proliferation. A symptomatic boy was diagnosed with DCLV at our hospital. The patient was admitted with the major complaint of 8 years of cardiac murmur, which was discovered through physical examination, and 5 years of palpitations and shortness of breath. He has been followed up without treatment.
Asunto(s)
Ecocardiografía/métodos , Cardiopatías Congénitas/diagnóstico por imagen , Ventrículos Cardíacos/anomalías , Ventrículos Cardíacos/diagnóstico por imagen , Niño , Diagnóstico Diferencial , Humanos , MasculinoRESUMEN
BACKGROUND: Primary cardiac tumors are rare, but few studies have examined the relationship between risk factors and the prognosis. The aim of this study was to provide a survival analysis and risk factors for mortality in patients with primary cardiac tumors. METHODS: We retrospectively enrolled 71 patients diagnosed with primary cardiac tumors from June 2006 to November 2017 in our hospital. Patients' population characteristics, treatment information, pathology, and follow-up data were obtained and analyzed. RESULTS: Of the 71 patients, 60 cases were benign, and 11 cases were malignant. Sex, age, New York Heart Association classification, the percentage of peripheral embolism, and surgery had no significant difference between benign and malignant groups (P >.05), but the percentage of arrhythmia, leg edema, and mortality rate was higher in the malignant tumor group than in the benign tumor group (P <.05). Compared with the benign tumor group, the percentage of biatrial lesions in the malignant tumor group was significantly higher (P <.05). Moreover, Independent risk factors included the treatment choice, pathology type, and number of tumor lesions (P <.05). CONCLUSION: Our study suggests that conservative therapy, malignant cardiac tumor, and biatrial tumor lesion are independent risk factors for poor prognosis.
Asunto(s)
Neoplasias Cardíacas/mortalidad , Neoplasias Cardíacas/cirugía , Adulto , China , Femenino , Neoplasias Cardíacas/patología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Tasa de SupervivenciaRESUMEN
To investigate the effects of the PI3K inhibitors on the differentiation of insulin-producing cells derived from human embryonic stem cells. Here, we report that human embryonic stem cells induced by phosphatidylinositol-3-kinase (PI3K) p110ß inhibitors could produce more mature islet-like cells. Findings were validated by immunofluorescence analysis, quantitative real-time PCR, insulin secretion in vitro and cell transplantation for the diabetic SCID mice. Immunofluorescence analysis revealed that unihormonal insulin-positive cells were predominant in cultures with rare polyhormonal cells. Real-time PCR data showed that islet-like cells expressed key markers of pancreatic endocrine hormones and mature pancreatic ß cells including MAFA. Furthermore, this study showed that the expression of most pancreatic endocrine hormones was similar between groups treated with the LY294002 (nonselective PI3K inhibitor) and TGX-221 (PI3K isoform selective inhibitors of class 1ß) derivatives. However, the level of insulin mRNA in TGX-221-treated cells was significantly higher than that in LY294002-treated cells. In addition, islet-like cells displayed glucose-stimulated insulin secretion in vitro. After transplantation, islet-like cells improved glycaemic control and ameliorated the survival outcome in diabetic mice. This study demonstrated an important role for PI3K p110ß in regulating the differentiation and maturation of islet-like cells derived from human embryonic stem cells.
Asunto(s)
Diferenciación Celular/efectos de los fármacos , Fosfatidilinositol 3-Quinasa Clase I/antagonistas & inhibidores , Células Madre Embrionarias Humanas/citología , Células Madre Embrionarias Humanas/efectos de los fármacos , Islotes Pancreáticos/citología , Islotes Pancreáticos/efectos de los fármacos , Inhibidores de Proteínas Quinasas/farmacología , Animales , Células Cultivadas , Cromonas/farmacología , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Células Madre Embrionarias Humanas/metabolismo , Humanos , Islotes Pancreáticos/metabolismo , Masculino , Ratones , Ratones SCID , Morfolinas/farmacología , Inhibidores de Proteínas Quinasas/química , Pirimidinonas/farmacología , Relación Estructura-ActividadRESUMEN
Objective To evaluate the feasibility and effectiveness of secundum atrial septal defect(ASD)occlusion with the septal occluder through right-chest small incision. Methods The clinical data of 140 secundum ASD patients (47 males and 93 females) aged 3-63 years who were treated in our center from August 2004 to July 2014 were retrospectively analyzed. The diameter of ASD was 6 to 36 mm. Under general anesthesia, all patients underwent intraoperative transtsophageal echocardiography (TEE), during which no associated cardiac deformity was found. All patients received ASD occlusion via a small incision (3-4 cm) at the right anterior chest. The occluders were released with the help of TEE. Results The atrial septal defect closure was successfully completed in 134 cases. Six cases received surgical closure of ASD after the failure of occlusion. The reasons of conversion included postoperative dislodgement of occlusion device (n=2, both were central type with large size) and technically unsuitable for occlusion (n=4, in whom residual shunt was found in 2 case, sieve pore type in 1 case, and intraoperative dislodgement in 1 case). All of these 6 patients were treated surgically under cardiopulmonary bypass. No dislocation of the device or atrial shunt was found within 3 to 48 months after the operation. Conclusion Occlusion via small chest incision of ASD under TEE guidance without cardiopulmonary bypass is a safe, minimally invasive, effective, and convenient treatment and worth clinical application.
Asunto(s)
Defectos del Tabique Interatrial/cirugía , Dispositivo Oclusor Septal , Adolescente , Adulto , Anestesia General , Puente Cardiopulmonar , Niño , Preescolar , Ecocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
Gliomas are the most common primary malignancy in the brain, accounting for 50-60%. Despite all the efforts of cytoreductive surgery in combination with intense chemoradiotherapy, glioma remains an incurable disease. Recent studies have shown that long noncoding RNAs (lncRNAs) are involved in the pathology of gliomas. LncRNAs are involved in many cellular processes, such as angiogenesis, invasion, cell proliferation, and apoptosis. In this review we focus on the dysregulation of lncRNAs in gliomas. We also address that epigenetic modification such as DNA methylation and microRNAs interact with lncRNAs in gliomas. In addition, the interaction of lncRNAs with signaling pathways in gliomas is discussed systematically, with particular emphasis on the interaction of lncRNAs with EZH2. Such approaches provide valuable insights into the potential future applications of lncRNAs in the treatment of gliomas.
Asunto(s)
Glioma/genética , Terapia Molecular Dirigida , Complejo Represivo Polycomb 2/genética , ARN Largo no Codificante/genética , Apoptosis/genética , Proliferación Celular/genética , Metilación de ADN/genética , Proteína Potenciadora del Homólogo Zeste 2 , Glioma/patología , Humanos , Invasividad Neoplásica/genética , Neovascularización Patológica/genética , Complejo Represivo Polycomb 2/biosíntesis , ARN Largo no Codificante/metabolismo , Transducción de SeñalRESUMEN
DNA methylation at the 5-position of cytosine (5mC) in the mammalian genome has emerged as a pivotal epigenetic event that plays important roles in development, aging and disease. The three members of the TET protein family, which convert 5mC to 5-hydroxymethylcytosine, has provided a potential mechanism resulting in DNA demethylation and maintaining cellular identity. Recent studies have shown that epigenetic modifications play a key role in the regulation of the molecular pathogenesis of gliomas. In this review we focus on demonstrating the TET proteins in DNA demethylation and transcriptional regulation of different target genes. In addition, we address the role of TET proteins in gliomas. This review will provide valuable insights into the potential targets of gliomas, and may open the possibility of novel therapeutic approaches to this fatal disease.
Asunto(s)
Neoplasias Encefálicas/metabolismo , Regulación Neoplásica de la Expresión Génica/fisiología , Glioma/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Metilación de ADN , Proteínas de Unión al ADN , Dioxigenasas , Humanos , Oxigenasas de Función MixtaRESUMEN
GPR137 are ubiquitously expressed in the central nervous system. However, the role o f GPR137 in human malignant glioma is still poorly known. In the present study, we firstly detected the expression of GPR137 in 29 human glioma tissue specimens by immunohistochemistry and in 5 malignant glioma cell lines by quantitative RT-PCR. The expression of GPR137 was much stronger in high-grade gliomas than in low-grade gliomas. Lentivirus-mediated small interfering RNAs (siRNAs) were employed to knock down GPR137 expression in glioma cells. Inhibition of GPR137 expression by RNAi significantly inhibited the proliferation and colony-forming capacity of U251, A172 and U373 cells. Moreover, flow cytometry analysis showed that knockdown of GPR137 led to the cell-cycle arrest at the S phase. Our results indicated that GPR137 is involved in the progression of human glioma, suggesting GPR137 as a potential oncogene of glioma cells.
Asunto(s)
Neoplasias Encefálicas/patología , Glioma/patología , Receptores Acoplados a Proteínas G/metabolismo , Western Blotting , Puntos de Control del Ciclo Celular/fisiología , Línea Celular Tumoral , Proliferación Celular/fisiología , Citometría de Flujo , Técnicas de Silenciamiento del Gen , Humanos , Inmunohistoquímica , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
BACKGROUND: Post-operative volume of subdural fluid is considered to correlate with recurrence in chronic subdural haematoma (CSDH). Information on the applications of computer-assisted volumetric analysis in patients with CSDHs is lacking. OBJECTIVE: To investigate the relationship between haematoma recurrence and longitudinal changes in subdural fluid volume using CT volumetric analysis. METHODS: Fifty-four patients harbouring 64 CSDHs were studied prospectively. The association between recurrence rate and CT findings were investigated. RESULTS: Eleven patients (20.4%) experienced post-operative recurrence. Higher pre-operative (over 120 ml) and/or pre-discharge subdural fluid volumes (over 22 ml) were significantly associated with recurrence; the probability of non-recurrence for values below these thresholds were 92.7% and 95.2%, respectively. CSDHs with larger pre-operative (over 15.1 mm) and/or residual (over 11.7 mm) widths also had significantly increased recurrence rates. Bilateral CSDHs were not found to be more likely to recur in this series. On receiver-operating characteristic curve, the areas under curve for the magnitude of changes in subdural fluid volume were greater than a single time-point measure of either width or volume of the subdural fluid cavity. CONCLUSIONS: Close imaging follow-up is important for CSDH patients for recurrence prediction. Using quantitative CT volumetric analysis, strong evidence was provided that changes in the residual fluid volume during the 'self-resolution' period can be used as significantly radiological predictors of recurrence.
Asunto(s)
Craniectomía Descompresiva , Hematoma Subdural Crónico/diagnóstico por imagen , Hematoma Subdural Crónico/patología , Tomografía Computarizada por Rayos X , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Hematoma Subdural Crónico/prevención & control , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Periodo Posoperatorio , Valor Predictivo de las Pruebas , Estudios Prospectivos , Recurrencia , Medición de Riesgo , Espacio Subdural/diagnóstico por imagen , Espacio Subdural/patologíaRESUMEN
BACKGROUND: Studies indicate that inflammation promotes progression of osteoarthritis. Cartilage damage is aggravated by the binding of toll-like receptors and endogenous ligands that release large amounts of cytokines and inflammation mediators. Calcitonin can inhibit degeneration of articular cartilage, by inhibiting activation of toll-like receptors and generation of endogenous ligands. To study the effect of calcitonin in the pathogenesis of osteoarthritis and the underlying molecular mechanism, we monitored levels of toll-like receptors during osteoarthritis progression, and after calcitonin injection. METHODS: Male Sprague-Dawley rats were randomly assigned to either a surgery-only or a calcitonin-treatment group (n = 35, each). To induce osteoarthritis, the anterior cruciate ligament and the medial meniscus were cut in the right knees of both groups. Rats in the calcitonin-treatment group received a subcutaneous injection of 15 IU/kg calcitonin once every other day, starting one day post-surgery, until euthanised. Signs of osteoarthritic changes were noted. The amount of collagen II was measured by antibody staining. The amounts of MMP1 and MMP3 in cartilage were measured by use of ELISA. RNA from operated and matched control knee cartilage was extracted to determine expression levels of Col2a1, ACAN, Tlr2, Tlr3, and Tlr4. RESULTS: Signs of osteoarthritis were less severe in rats treated with calcitonin. In the surgery-only group, Tlr2 levels increased early after surgery and then decreased substantially by the latter stages. Tlr3 levels gradually increased and correlated with the severity of osteoarthritis. Tlr4 levels were high but fluctuated over the experimental period. Calcitonin treatment was associated with lower Tlr3 and Tlr4 levels than in the surgery-only group whereas Tlr2 expression was initially lower but increased 28 days after administration of calcitonin. CONCLUSION: Calcitonin treatment may lessen the severity of osteoarthritis in the rat model, perhaps by inhibition of Tlr expression in cartilage.
Asunto(s)
Calcitonina/uso terapéutico , Osteoartritis de la Rodilla/tratamiento farmacológico , Receptores Toll-Like/metabolismo , Animales , Conservadores de la Densidad Ósea/uso terapéutico , Cartílago/metabolismo , Cartílago/patología , Modelos Animales de Enfermedad , Ensayo de Inmunoadsorción Enzimática , Regulación de la Expresión Génica , Inmunohistoquímica , Masculino , Osteoartritis de la Rodilla/diagnóstico , Osteoartritis de la Rodilla/genética , ARN/genética , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Índice de Severidad de la Enfermedad , Receptores Toll-Like/genéticaRESUMEN
In order to research the residual mechanical properties of concrete shield tunnel segments after exposure to high temperatures, two types of concrete segments were designed: a self-compacting concrete segment and a mixed fiber (steel fiber and polypropylene fiber) self-compacting concrete segment. The mechanical properties of seven blocks of concrete segments (five segments after high-temperature exposure and two segments at room temperature) were tested to analyze the influence of different loading sizes and fibers on the development of cracks after high temperature, failure mode, crack width, deformation, and so on in the concrete segments. The results showed that the damage model of the segment after exposure to high temperature and the segment at room temperature were crushed in the pressurized zone, but the high temperature had little effect on the concrete in the pressurized area. The size of the preload at high temperatures had little effect on the remaining load capacity, and the effect on the number of cracks was mainly concentrated on the internal arc surface of the segment. After high-temperature exposure, the number of cracks on the sides and inner arc surface of the segment increased, and the development of cracks was concentrated as several major cracks at high temperatures. When fibers were incorporated, the cracks in the segment became obvious, where the cracks at the loading point became denser and the interval distance became smaller.
RESUMEN
BACKGROUND: Gustilo III fractures have a high incidence and are difficult to treat. Patients often experience difficulty in wound healing. Negative pressure drainage technology can help shorten wound healing time and has positive value in improving patient prognosis. AIM: To explore the clinical value of the negative pressure sealing drainage technique in wound healing of Gustilo IIIB and IIIC open fractures. METHODS: Eighty patients with Gustilo IIIB and IIIC open fractures with skin and soft tissue injuries who were treated in the Second People's Hospital of Dalian from March 2019 to December 2021 were selected as the research subjects. They were divided into a study group (n = 40, healed with negative pressure closed drainage) and a control group (n = 40, healed with conventional dressing changes) according to the variation in the healing they received. The efficacy of the clinical interventions, the variations in the regression indicators (time to wound healing, time to fracture healing, time to hospitalization), and the conversion and healing of bacterial wounds were compared 1-3 mo after the intervention. RESULTS: The total effective rate of patients among the study group was 95.00% (38/40), which was notably higher than 75.00% (30/40) among the control group (P < 0.05). The wound healing time, fracture healing time, and hospital stay of the patients in the study group was shorter than the control group (P < 0.05). After the intervention, the negative bacterial culture at the wound site rate and wound healing rate of the patients among the study group increased compared to the control group (P < 0.05). CONCLUSION: Negative pressure sealing and drainage technology has a good therapeutic effect on patients with Gustilo IIIB and IIIC open fracture wounds with skin and soft tissue injury. It can notably enhance the wound healing rate and the negative rate of bacteria on the wound surface and help to speed up the recovery process of patients.
RESUMEN
Background: Rheumatoid arthritis (RA) is a systemic immune-related disease characterized by synovial inflammation and destruction of joint cartilage. The pathogenesis of RA remains unclear, and diagnostic markers with high sensitivity and specificity are needed urgently. This study aims to identify potential biomarkers in the synovium for diagnosing RA and to investigate their association with immune infiltration. Methods: We downloaded four datasets containing 51 RA and 36 healthy synovium samples from the Gene Expression Omnibus database. Differentially expressed genes were identified using R. Then, various enrichment analyses were conducted. Subsequently, weighted gene co-expression network analysis (WGCNA), random forest (RF), support vector machine-recursive feature elimination (SVM-RFE), and least absolute shrinkage and selection operator (LASSO) were used to identify the hub genes for RA diagnosis. Receiver operating characteristic curves and nomogram models were used to validate the specificity and sensitivity of hub genes. Additionally, we analyzed the infiltration levels of 28 immune cells in the expression profile and their relationship with the hub genes using single-sample gene set enrichment analysis. Results: Three hub genes, namely, ribonucleotide reductase regulatory subunit M2 (RRM2), DLG-associated protein 5 (DLGAP5), and kinesin family member 11 (KIF11), were identified through WGCNA, LASSO, SVM-RFE, and RF algorithms. These hub genes correlated strongly with T cells, natural killer cells, and macrophage cells as indicated by immune cell infiltration analysis. Conclusion: RRM2, DLGAP5, and KIF11 could serve as potential diagnostic indicators and treatment targets for RA. The infiltration of immune cells offers additional insights into the underlying mechanisms involved in the progression of RA.