ABSTRACT
Objective@#To investigate the diagnosis, treatment and prognosis of nonodontogenic periapical lesions and to provide a reference for clinical diagnosis and treatment.@*Methods@# A case of a patient with right upper molar pulp with apical penetration and local occlusion admitted to the West China Stomatological Hospital of Sichuan University was retrospectively analyzed, and the curative effect of microapical surgery and pith preservation was also analyzed.@*Results @#The imaging features of tooth 16 showed periradicular radiolucency combined with local radiopaque lesions around the distal buccal apical area. Endodontic microsurgery was performed under local anesthesia. Soft tissue coverage was observed in the distal buccal apical area during the surgery, and no radiopaque tissue was detected. The distal buccal root apex was cut by 3 mm, and mineral trioxide aggregate was used for root-end backfilling. The postoperative pathological results revealed fibrous connective tissue. One-week recall X-ray examination showed tight root-end backfilling and no periradicular radiolucency; an electrical test of pulp vitality showed positive results. The four-year follow-up showed that there was no discoloration in tooth 16 and no significant difference in thermal and electrical tests of pulp vitality compared with control teeth. Combining the clinical manifestations, imaging features, surgical exploration results and pathological reports, the case was most likely to be cemental hypoplasia. Through the literature review, the treatment and healthy pulp preservation of such cases by endodontic microsurgery under the premise of preserving teeth has not been reported.@*Conclusion@#For maxillary posterior teeth with periapical lesions but healthy pulp, accurate estimation of pulp status, endodontic microsurgical exploration and application of bioactive materials can achieve vital pulp preservation while removing the lesions.
ABSTRACT
@#Cardiac rehabilitation can safely and effectively improve the quality of patient's life and reduce readmission rate and mortality after cardiac surgery. Early cardiac rehabilitation after cardiac surgery is an indispensable part of cardiac rehabilitation. It can speed up the recovery of patient's exercise endurance, prevention of postoperative complications, shorten the time of returning to the family, increase the confidence of sustained rehabilitation, and lay foundation and set rehabilitation targets for the later stage of cardiac rehabilitation. This paper reviews the development history of early cardiac rehabilitation after cardiac surgery, and summarizes the current status, problems and outlook of rehabilitation management in China.
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OBJECTIVE To discover a small- molecule activator of ULK1 for Parkinson disease treatment and exploreits potential mechanisms. METHODS Candidate ULK1 activator was found by using structure-based design and high-through put screening, then modified by chemical synthesis and screened by kinase and autophgic activities.The amino acid residues that key to the activation site of the best candidate ULK1 activator (BL-918) were determined by site-directed mutagenesis, as well as in vitro kinase assay, ADP- Glo kinase assay and surface plasmon resonance (SPR) analysis. The mechanisms of BL- 918 induced cytoprotective autophagy were investigated by electron microscopy, fluorescence microscopy, Western blotting, co-immunoprecipitation assay, siRNA and GFP-LC3 plasmid transfections. The therapeutic effect of BL- 918 was determined by MPTP- mouse model, including behavioral tests, the levels of dopamine and its derivatives, as well as immunofluorescence and Western blotting. The toxicity of BL-918 was assessed by blood sample analysis and hematoxylin-eosin staining. RESULTS We discovered a small molecule (BL-918) as a potent activator of ULK1 by structure-based drug design. Subsequently, some key amino acid residues (Arg18, Lys50, Asn86 and Tyr89) were found to be crucial to the binding pocket between ULK1 and BL- 918, by site- directed mutagenesis. Moreover, we found that BL- 918 could induce autophagy via the ULK complex in neuroblastoma SH-SY5Y cells. Intriguingly, this activator displayed a cytoprotective effect on MPP +-treated SH-SY5Y cells, as well as protected against MPTP-induced motor dysfunction and loss of dopaminergic neurons by targeting ULK1- modulated autophagy in mouse models of PD. CONCLUSION We discovered a novel ULK1 activator (BL-918) that potently activated ULK1. This activator could induce cytoprotective autophagy via the ULK1 complex in SH- SY5Y cells, and also exerted its neuroprotective effects by targeting ULK1- modulated autophagy in a MPTP- induced PD mouse model, which may serve as a candidate drug for future PD therapy.
ABSTRACT
BACKGROUND: Human amnion mesenchymal cells (hAMCs), isolated from the amniotic membrane of human placenta, are a unique population of mesenchymal stem cells. Recent studies demonstrated that hAMCs could inhibit the activities and functions of several immune cells. However, their effect on inflammatory macrophages is largely unknown. This study investigated the effect of hAMCs on expression of inflammatory cytokines and mitogen-activated protein kinases (MAPKs)/NF-kB pathway in human THP-1 macrophages induced by lipopolysaccharide (LPS). RESULTS: The levels of TNF-α and IL-1ß secreted by LPS- stimulated THP-1 cells were increased significantly compared with those in the control group. After co-culture with different numbers of hAMCs, the levels of TNF-α and IL-1ß in LPS-stimulated THP-1 cells were significantly reduced compared with the LPS group. The mRNA expression of TNF-α and IL-1ß were also markedly inhibited. Moreover, treating LPS-stimulated THP-1 cells with hAMCs supernatants could also suppress TNF-α and IL-1ß production in THP-1 cells. Important signaling pathways involved in the production of TNF-α and IL-1ß were affected by hAMCs co-culture: hAMCs remarkably suppressed NF-kB activation and down-regulated the phosphorylation of ERK and JNK in LPS- stimulated THP-1 cells. CONCLUSIONS: Human amnion mesenchymal cells inhibited the production of TNF-α and IL-1ß secreted by LPS-stimulated THP-1 cells, partly through the suppression of NF-kB activation and ERK and JNK phosphorylation.