Current models of somatosensory perception emphasize transmission from primary sensory neurons to the spinal cord and on to the brain. Mental influence on perception is largely assumed to occur locally within the brain. Here we investigate whether sensory inflow through the spinal cord undergoes direct top-down control by the cortex. Although the corticospinal tract (CST) is traditionally viewed as a primary motor pathway, a subset of corticospinal neurons (CSNs) originating in the primary and secondary somatosensory cortex directly innervate the spinal dorsal horn via CST axons. Either reduction in somatosensory CSN activity or transection of the CST in mice selectively impairs behavioural responses to light touch without altering responses to noxious stimuli. Moreover, such CSN manipulation greatly attenuates tactile allodynia in a model of peripheral neuropathic pain. Tactile stimulation activates somatosensory CSNs, and their corticospinal projections facilitate light-touch-evoked activity of cholecystokinin interneurons in the deep dorsal horn. This touch-driven feed-forward spinal-cortical-spinal sensitization loop is important for the recruitment of spinal nociceptive neurons under tactile allodynia. These results reveal direct cortical modulation of normal and pathological tactile sensory processing in the spinal cord and open up opportunities for new treatments for neuropathic pain.
BackgroundPrevious studies have shown that differences in marital status contribute to different prognoses for certain cancers, but the relationship between marital status and the prognosis of chondrosarcoma has not been reported previously.Material/MethodsIn this study, we selected 4502 eligible cases through the Surveillance, Epidemiology, and End Results (SEER) database from 1977 to 2014 to analyze the impact of marital status on chondrosarcoma cancer-specific survival (CSS) by Kaplan-Meier method and Cox regression model.ResultsThe sex, age, histotype, pathological grade, tumor location, tumor size, SEER stage, socioeconomic status, marital status, and treatment were identified as independent prognostic factors for chondrosarcoma CSS. Widowed patients presented the worst CSS compared with their married, divorced, and single counterparts (P<0.001). Subgroup analyses showed widowed patients also had a significantly higher risk of cancer-specific mortality compared with married patients in localized stage (HR: 1.971, 95% CI: 1.298–2.994, P=0.001), regional stage (HR: 1.535, 95% CI: 1.094–2.154, P=0.013), low pathological grade (HR: 1.866, 95% CI: 1.332–2.613, P<0.001), and high pathological grade (HR: 1.662, 95% CI: 1.139–2.426, P=0.008).ConclusionsMarital status was first identified as an independent prognostic factor for chondrosarcoma CSS, and widowhood was always associated with a high risk of cancer-specific mortality. It is necessary to provide timely psychological treatment for widowed patients in clinical practice, which can improve the survival of chondrosarcoma patients.
Background:Infections caused by strains with multi-drug resistance are difficult to treat with standard antibiotics. Garlic is a powerful remedy to protect against infections of many bacteria, fungi and viruses. However, little is known about the potentials of fresh garlic extract (FGE) to improve the sensitivity of multi-drug resistant strains to antibiotics.Objectives:In this study, we used the disk diffusion method to investigate the antimicrobial activities of FGE and the combination of antibiotics with FGE, on methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa and Candida albicans, to evaluate the interactions between antibiotics and FGE.Materials and Methods:Clinical isolates were isolated from clinical specimens obtained from the inpatients at the First Affiliated Hospital of Xi’an Jiaotong University Health Science Center. The isolates consisted of MRSA, (n = 30), C. albicans (n = 30) and P. aeruginosa (n = 30). Quality control for CLSI (Clinical and Laboratory Standards Institute) disk diffusion was performed using S. aureus ATCC®25923, C. albicans ATCC®90028 and P. aeruginosa ATCC®27853. The 93 microorganisms were divided into four groups in a factorial design: control (deionized water), FGE, antibiotics without FGE, and antibiotics with FGE. Next, antibacterial activity was evaluated by measuring the diameter of inhibition zones according to performance standards for antimicrobial susceptibility testing of the Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS).Results:Fresh garlic extract displayed evident inhibition properties against C. albicans and MRSA, yet weak inhibition properties against P. aeruginosa. Additionally, FGE showed the potential to improve the effect of antibiotics on antibiotic resistant pathogens. The synergism of fluconazole and itraconazole with FGE on C. albicans yielded larger sized inhibition zones compared with fluconazole and itraconazole without FGE (P < 0.01). The factorial analysis represents intense positive interaction effects (P < 0.01). The synergism of cefotaxime and ceftriaxone with FGE on P. aeruginosa yielded larger sized inhibition zones than cefotaxime and ceftriaxone without FGE (P < 0.01). The factorial analysis represents intense positive interaction effects (P < 0.01).Conclusions:The results suggest that FGE can improve the antibiotic sensitivity of these pathogens to some antibiotics.
Osteosarcoma (OS) is the major type of primary bone tumor and is associated with a poor prognosis due to chemotherapy resistance. Accumulating evidence indicates that microRNAs (miRNAs/miRs) may influence the tumor progression of OS and cell sensitivity to chemotherapy. In the present study, a total of 7 patients with OS and 7 healthy volunteers were recruited. Reverse transcription-quantitative polymerase chain reaction and ELISA were performed to determine the expression of miRNAs and mRNAs in the serum of participants. Furthermore, the biological function of miR-22 and S100A11 was examined in MG-63 cells using Cell Counting Kit-8 assays, Transwell migration assays and western blot analysis to determine the effects on cell proliferation, migration and protein expression, respectively, while MG-63 cell sensitivity to cisplatin was assessed by measuring cell viability following cisplatin treatment and calculating the half maximal inhibitory concentration (IC50). Additionally, the association between miR-22 and S100 calcium-binding protein A11 (S100A11) was validated using a luciferase reporter assay. The results demonstrated that miR-22 expression was significantly reduced in patients with OS and the MG-63 OS cell line, compared with healthy volunteers and the normal osteoblast hFOB 1.19 cell line, respectively, while the expression of S100A11 was negatively associated with miR-22 levels in the MG-63 cell line. Furthermore, overexpression of miR-22 inhibited the proliferation and migratory ability of MG-63 cells, and increased the sensitivity of MG-63 cells to cisplatin treatment; however, overexpression of S100A11 partially attenuated the alterations in proliferation, migratory ability and chemosensitivity that were induced by miR-22 overexpression. In addition, it was confirmed that S100A11 is a direct target gene of miR-22 in MG-63 cells. In conclusion, to the best of our knowledge, the present study is the first to demonstrate that miR-22 may be a promising therapeutic target and may have potential as part of a combination treatment alongside chemotherapeutic agents for OS.
Background Anterior cervical plate and cage fixation system (ACPC) used in anterior cervical corpectomy and fusion (ACCF) is reported to incur excess complications. This study aimed to introduce integrated fixation cage (IFC) into ACCF to eliminate the anterior cervical plate (ACP)-related complications. Material/Methods One validated intact and 3 ACCF-simulated C3–C7 cervical spine models were developed. In ACCF models, C5 was corpectomied and fixed by IFC or ACPC. For each model, 1.0 Nm moments of flexion, extension, lateral bending, and torsion were imposed on the C3 vertebra. The range of motion (ROM) of each segment and the stress distribution on screw-vertebra interface, bone graft, and cage-endplate were recorded and analyzed. Results ROMs of C3–C7 were not different in any motion condition between IFC and ACPC models. The maximal von Mises stress on screw-vertebra interface of the IFC model was lower than that of the ACPC models in flexion, extension, and lateral bending, but higher in rotation. The maximal von Mises stress on bone graft of the IFC model was higher compared with the ACPC models, except in flexion. The IFC model showed a higher maximal von Mises stress on cage-endplate interface in all motion planes. Conclusions Based on finite element analysis, IFC provided identical C3–C7 construct stability as ACPC. Compared with ACPC, IFC showed better biomechanical performance on screw-vertebra interface and bone graft, but worse biomechanical performance on cage-endplate interface.
Background: The establishment of precise and personalized prediction systems for chondroblastic osteosarcoma patients is important for guiding the treatment. Methods: The univariate logrank test and multivariate Cox regression analysis were performed to identify independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS). Nomograms were constructed to estimate the OS and CSS based on these factors. Internal and external validation was performed. The predictive power of the nomograms was determined by C-index and calibration plots. Results: A total of 401 chondroblastic osteosarcoma cases were identified. Univariate and multivariate analysis revealed that age at diagnosis, histological grade, tumor size, Surveillance, Epidemiology, and End Results stage, and surgical resection were independent prognostic factors for OS and CSS. The five factors were incorporated to construct the nomograms for estimating the 3-and 5-year OS and CSS. The C-index values for the internal validation of the OS and CSS nomogram were 0.732 and 0.746, respectively, and for the external validation were 0.780 and 0.808, respectively. The calibration curves revealed that the predicted OS and CSS could well match the actual survival rate. Conclusions: The nomograms for predicting 3-and 5-year OS and CSS were constructed and were proved to be accurate and reliable by the internal and external validation.
BackgroundThe goal of this study was to determine the prognostic factors exclusive for high-grade chondrosarcoma and whether adjuvant radiotherapy could achieve better overall survival (OS) or cancer-specific survival (CSS) for patients with high-grade chondrosarcoma.Material/MethodsSurveillance, Epidemiology, and End Results (SEER) cancer registry database was utilized to extract the chondrosarcoma cases diagnosed between 1973 and 2014. Among these cases, the histological grades of poorly differentiated (grade 3) and undifferentiated (grade 4) were categorized as high-grade and included in this study. Chondrosarcoma OS and CSS were the primary outcomes in the present study. The log-rank test was performed for univariate analysis, and the Cox regression model was conducted for multivariate analysis.ResultsA total of 743 patients with high-grade chondrosarcoma were identified in this study (430 cases were poorly differentiated tumors, and 313 cases were undifferentiated tumors). Age at diagnosis, pathological grade, histo-type, SEER stage, tumor size and surgical resection were identified as independent predictors in both OS and CSS analysis of high-grade chondrosarcoma. When stratified by histological grade, surgical resection remained the effective treatment. Strikingly, radiotherapy was determined as an independent protective factor in both OS and CSS analysis of undifferentiated (grade 4) dedifferentiated chondrosarcoma, and adjuvant radiotherapy combined surgical resection could improve both the OS and CSS of patients with undifferentiated myxoid and dedifferentiated chondrosarcoma compared with other treatment regimens.ConclusionsOur study first demonstrated that adjuvant radiotherapy combined surgery could improve the survival of patients with undifferentiated myxoid and dedifferentiated chondrosarcoma. These results encourage the application of adjuvant radiotherapy for patients with high-grade chondrosarcoma and maximize the patients’ outcome.
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