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OBJECTIVES: This study aims to evaluate the safety and efficacy of BCMA-CD19 compound chimeric antigen receptor T cells (cCAR) to dual reset the humoral and B cell immune system in patients with systemic lupus erythematosus (SLE) with lupus nephritis (LN). METHODS: This is a single-arm open-label multicentre phase 1 study of BCMA and CD19-directed cCAR in patients suffering from SLE/LN with autoantibodies produced by B cells and plasma/long-lived plasma cells. In this clinical trial, we sequentially assigned biopsy-confirmed (classes III-V) LN patients to receive 3×106 cCAR cells/kg postcessation of all SLE medications and conditioning. The primary endpoint of safety and toxicity was assessed. Complete immune reset was indicated by B cell receptor (BCR) deep sequencing and flow cytometry analysis. Patient 11 (P11) had insufficient lymphocyte counts and was underdosed as compassionate use. RESULTS: P1 and P2 achieved symptom and medication-free remission (MFR) from SLE and complete remission from lymphoma. P3-P13 (excluding P11) received an initial dose of 3×106 cCAR cells /kg and were negative for all autoantibodies, including those derived from long-lived plasma cells, 3 months post-cCAR and the complement returned to normal levels. These patients achieved symptom and MFR with post-cCAR follow-up to 46 months. Complete recovery of B cells was seen in 2-6 months post-cCAR. Mean SLE Disease Activity Index 2000 reduced from 10.6 (baseline) to 2.7 (3 months), and renal function significantly improved in 10 LN patients ≤90 days post-cCAR. cCAR T therapy was well tolerant with mild cytokine-release syndrome. CONCLUSIONS: Data suggest that cCAR therapy was safe and effective in inducing MFR and depleting disease-causing autoantibodies in patients with SLE.
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Objective: The aim of this review is to provide guidance on the selection of approaches to the screening and assessment of enthesitis in patients with spondyloarthritis (SpA). Methods: Twenty-four questions regarding the approaches to the screening and assessment of enthesitis and the implementation details were devised, followed by a systemic literature review. The Grading of Recommendations Assessment, Development, and Evaluation methodology was employed in the development of this guideline, with modifications to evaluate non-interventional approaches under comprehensive consideration of costs, accessibility, and evidence strength. A consensus from the voting panel was required for the inclusion of the final recommendations and the strength of each recommendation. Results: Seventeen recommendations (including five strong recommendations) were included in this guideline. The voting panel expressed unequivocal support for the necessity of screening and assessment of enthesitis in patients with SpA. It was agreed unanimously that symptom evaluation and physical examination should serve as the initial steps to the recognition of enthesitis, whereas Maastricht Ankylosing Spondylitis Enthesitis Score is a reliable tool in both clinical trials and daily medical practice. Ultrasound examination is another reliable tool, with power Doppler ultrasound as an informative addition. Notwithstanding its high resolution, MRI is limited by the costs and relatively low accessibility, whereas radiographs had low sensitivity and therefore should be rendered obsolete in the assessment of enthesitis. PET/CT was strongly opposed in the detection of enthesitis. Conclusion: This guideline provides clinicians with information regarding the screening and assessment of enthesitis in patients with SpA. However, this guideline does not intend on dictating choices, and the ultimate decisions should be made in light of the actual circumstances of the facilities.
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Espondiloartritis , Espondilitis Anquilosante , Humanos , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones , Espondiloartritis/diagnóstico , Espondilitis Anquilosante/tratamiento farmacológicoRESUMEN
PURPOSE: To investigate miR-99a expression and its effect on proliferation of oral squamous cell carcinoma (OSCC). METHODS: miRNA microarrays associated with OSCC were identified in GEO database. The expression levels of miR-99a were detected in 63 OSCC tissues and adjacent normal tissues and cell lines. The relationship between clinicopathological parameters and miR-99a expression was analyzed by using ANOVA analysis. The ability of cell growth and clone formation were examined in SCC9 and SCC25 cells transfected with miR-99a mimics. The target genes of miR-99a were predicted by Targetscan software. There resulting data were analyzed using SPSS 19.0 software package. RESULTS: The differently expressed miRNAs were analyzed based on GSE103931 microarray. miR-99a was significantly downregulated in OSCC tissues and cell lines. miR-99a expression was significantly associated with T stage, pathological grading and patients' prognosis. miR-99a overexpression inhibited OSCC cell proliferation and clone formation, while miR-99a inhibition contributed to decreased proliferation and clone formation ability. In addition, miR-99a combined with mTOR gene's 3'UTR was negatively correlated with mTOR expression in OSCC tissues. CONCLUSIONS: miR-99a functions as a tumor suppressor in OSCC and inhibits OSCC cell proliferation by targeting mTOR.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , MicroARNs , Neoplasias de la Boca , Carcinoma de Células Escamosas/genética , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , MicroARNs/genética , Neoplasias de la Boca/genética , Carcinoma de Células Escamosas de Cabeza y Cuello , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Objective@#To evaluate the value of Kirschner wire internal fixation in the treatment of sagittal mandibular condylar fractures.@*.Methods @#From January 2019 to January 2020, 13 patients (19 sides) with mandibular condylar sagittal fracture treated by Kirschner wire internal fixation at the Stomatological Medical Center, Foshan Hospital of Traditional Chinese Medicine were retrospectively analyzed. After conventional surgical incision and exposure and reduction of the mandibular condyle, 2-4 Kirschner wires were used for fixation, and other maxillofacial fractures were treated simultaneously. The reduction accuracy and stability of the free mandibular condyle were evaluated by CBCT one week after the operation, and the occlusion relationship, opening degree and opening type were evaluated by clinical examination.@*Results@#All patients had good fracture alignment and no twisting, breaking or loosening of the Kirschner wire. The occlusion relationship, opening degree and opening shape recovered well after the operation.@*Conclusion@# Kirschner wire is effective in treating sagittal fractures of mandibular condyles.
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Objective @#To explore the effect of negative pressure sealing drainage on the treatment of maxillofacial-neck-mediastinal infection in multiple spaces.@*Methods@# Vacuum sealing drainage (VSD) was applied in five patients with maxillofacial-neck-mediastinal infection caused by odontogenic infection accompanied by diabetes or renal failure and other systemic diseases. After extensive debridement, a negative pressure drainage sponge was placed in the pus cavity and then the wound was closed. Continuous negative pressure drainage was continued after the operation. At the same time, multidisciplinary consultation was applied to control basic diseases and, strengthen anti-inflammatory responses, and nutrition and other systemic treatments were applied.@*Results@#Four patients underwent continuous negative pressure drainage and successful removal of the negative pressure sponge after inflammatory symptoms subsided. One patient′s inflammatory symptoms became more serious after the operation, and we performed another operation to change the placement of the negative pressure sponge. All 5 patients underwent VSD with negative pressure sponge replacement ranging from 1 to 3 times during treatment. After multidisciplinary consultation, they were all cured and discharged from the hospital.@*Conclusion@#For infection of the mediastinum, maxillofacial region and neck, local treatment and systemic treatment are emphasized, as well as the treatment of infected lesions and basic diseases. Negative pressure closure and drainage technology promotes the alleviation of inflammation, and multidisciplinary combined treatment is beneficial for the control of basic diseases.
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@#Osseointegration plays an important role in the functions and aesthetics of dental implant. This paper focus on the hormones closely related to the bone metabolism, including glucocorticoid, parathyroid hormone, calcitonin, melatonin, and oestrogen, and reviews the influence of hormones on the osseointegration.
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Objective @#To explore the effects of mouth floor approach intubation in the treatment of jaw fracture combined with skull base injury.@*Methods @#From Jan. 2014 to Oct. 2015, 7 cases of jaw fracture combined with skull base injury were selected from Medical center of Stomatology, Foshan Hospital of Traditional Chinese Medicine (FSTCM). All cases were treated with mouth floor approach intubation, because they were not suitable to be given the oral or nasal intubation anesthesia. @*Results @#All the patients healed well after operation, and there was no tube accident or other complications.@*Conclusions@# For patients of jaw fracture combined with skull base injury, the mouth floor approach intubation could be recommended as a supplementary choice for traditional intubation methods.