At present, most clinical thrombolytic drugs are plasminogen activators, which are highly dependent on the plasminogen level of the patient. Therefore, the efficacy of those drugs is restricted. Unlike the conventional thrombolytic plasminogen activator drugs, fibrinolytic drugs have direct fibrinolytic activity. Thus, fibrinolytic drugs can directly dissolve the thrombus, and its thromlysis efficacy is not restricted by the patients' plasminogen. This is a new type of thrombolytic drug with higher thrombolytic efficiency and safety, and has become one of the research hotspots at present. Although more and more agents that can be used as fibrinolytic drugs have been discovered, only a few of them can successfully be applied in clinical practice. The mainly underlying reason is the risk of bleeding. In this paper, based on the latest research progress of fibrinolytic drugs, the bleeding mechanisms and coping strategies of fibrinolytic drugs were systematically reviewed, five types of bleeding mechanisms of fibrinolytic drugs were summarized, and three types of coping strategies were proposed. We hope our work can provide theoretical basis for the development of safer and more efficient fibrinolytic drugs.

Animals ; Aorta ; drug effects ; physiology ; Blood Pressure ; drug effects ; Cadmium ; toxicity ; Female ; In Vitro Techniques ; Male ; Muscle, Smooth, Vascular ; drug effects ; physiology ; Rabbits ; Vasoconstriction ; drug effects

Human tissue kallikrein-binding protein (Kallistatin, KAL), a secretory protein that participates in the regulation of multiple signaling pathways by binding to the extracellular receptor, however, at present has not been reported about the intracellular activity, and whether it has the similar biological activity with extracellular activity. Here we constructed no signal peptide KAL (NSK) into the adeno-associated virus vector to explore the intracellular activity of KAL. Both the endothelial cell and lung cancer cells could express KAL, but not secreted after rAAV2-NSK transfection. The proliferation and migration of human umbilical vein endothelial cells (HUVECs) were inhibited, but the apoptosis rate was not affected. The proliferation rates, mobility and tubule formation of all the three tested lung cancer cells, such as NCI-H446, NCI-H460 and A549, were inhibited to different extents. This cellular study not only confirmed the intracellular activity, but also suggested it may serve as a kind of "balance factor" in multi-targeted controlling, which may provide a new train of thoughts to explain the regulatory contradiction in PI3K-Akt signaling pathways by KAL.
Apoptosis ; Cell Proliferation ; Dependovirus ; Genetic Vectors ; Human Umbilical Vein Endothelial Cells ; metabolism ; Humans ; Lung Neoplasms ; metabolism ; Serpins ; metabolism ; Signal Transduction ; Transfection

The purpose of the study was to observe the effect of rapamycin (RAPA) on the differentiation and maturation of rat bone marrow-derived dendritic cells (BMDCs) in vitro. BMDCs from Wistar rats were cultured with granulocyte-macrophage colony-stimulating factor plus interleukin-4 in the presence or absence of RAPA (20 ng/mL), and stimulated with lipopolysaccharide (LPS) for 24 h before cells and supernatants were collected. Surface phenotype of BMDCs was flow-cytometrically detected to determine the expression of maturation markers, MHC class II and CD86. Supernatants were analyzed for the production of IL-12 and IFN-gamma cytokines by using ELISA. BMDCs were co-cultured with T cells from Lewis rats and mixed lymphocyte reaction was assessed by MTT method. The morphology of BMDCs stimulated with LPS remained immature after RAPA pretreatment. RAPA significantly decreased the CD86 expression, impaired the IL-12 and IFN-gamma production of BMDCs stimulated with LPS, and inhibited the proliferation of allogeneic T cells. In conclusion, RAPA can inhibit the maturation of BMDCs stimulated with LPS in terms of the morphology, surface phenotype, cytokine production, and ability of BMDCs to stimulate the proliferation of allogeneic T cells in vitro.

Objective To analyze the cause of acute brain swelling,brain encephalocele in brain traumatic injury craniotomy,and the reason,diagnosis and treatment methods of progressive epidural hematoma.Methods The clinical data of 381 patients with brain traumatic injury craniotomy were retrospetively analyzed.Of 318 patients,27cases had progressive epidural hematoma during operation.Results 9 cases died because of functional failure of brain stem,the other 18 cases were all clinically cured.Conclusion If acute brain swelling and encephalocele occured during operation,the cause should be found quickly,especially when there was skull fracture or epidural hematoma on the contralateral brain,the head CT and operation should be taken immediately,and the bulging brain tissue should not be removed blindly,and the skull should not be forced to close,otherwise the prognosis maybe poor.

Adult ; Diagnosis, Differential ; Follow-Up Studies ; Humans ; Knee Joint ; Male ; Mucin-1 ; metabolism ; Neurilemmoma ; metabolism ; pathology ; surgery ; S100 Proteins ; metabolism ; Sarcoma, Synovial ; metabolism ; pathology ; Sweat Glands

BACKGROUND:Oversize stress of a dental implant and its surrounding tissue is the main factor to affect the
long-term use of dental implants. So, the reasonable and precise design of implant shape is one of the important methods of prolonging the life span of dental implants.
OBJECTIVE:To make the optimal analysis and design of the diameters of connector screw and central screw of the adjustable-angle dental implant invented in the earlier stage.
METHODS: The finite element analysis model of the edentulous mandible with adjustable-angle dental implant was established by software Pro/E 5.0, Mimics 10.0 and ANSYS Workbench 14.5. The maximum equivalent
stress of dental implant-edentulous mandibular model was analyzed.
RESULTS AND CONCLUSION:The maximum equivalent stress of dental implant-edentulous mandibular model

Objective:To evaluate the effects of dexamethasone on systemic lupus erythematosus complicated with cognitive dysfunction.Methods:Ten wild type mice and 20 MRL/lpr mice were applied for the research.MRL/lpr mice were randomly assigned to a MRL/lpr group and a MRL/lpr + dexamethasone (1.5 mg/kg) group.Interleukin-6 (IL-6),IL-1β,and tumor necrosis factor alpha (TNF-α) in serum and hippocampus were detected.The protein phosphorylation levels of phosphoinositide 3-kinase (P-PI3K),protein kinase B (P-Akt),NF-kappa-B inhibitor alpha (P-IκBa) and nuclear transcription factor kappa-B p65 (P-NF-κB p65) were detected by Western blot,the level of P-NF-κB p65 also was detected by immunohistochemistry.Results:Treatment with dexamethasone (1.5 mg/kg) alleviated the cognitive dysfunction and decreased the levels of IL-6,IL-1 β and TNF-α in serum and hippocampus,and reduced the levels of P-PI3K,P-Akt,P-IκBa and P-NF-κB p65 in hippocampus in MRL/lpr mice.Conclusion:Dexamethasone may play a protective role in the cognitive function by decreasing the levels of TNF-α and IL-1 β in the hippocampus of MRL/lpr lupus mice.

Objective:To construct an evaluation the index system of entrustable professional activities for resident training doctors in psychiatric department,and to provide reference for formulating training strategies and assessment standards.Entrustable professional activities refers to the ability of trainees to perform and complete spe-cific clinical tasks independently after they have been trusted.Methods:Through documental analysis and semi-structured interviews,the item database of entrustable professional activities for psychiatric resident training physi-cians was established.Delphi consultation was conducted among 63 experts in the field of psychiatry from 7 national resident training bases and 3 medical colleges in China.Indicators were comprehensively screened and sorted out,and indicators at all levels and their weights were determined by the analytic hierarchy process.Results:A hierarchi-cal evaluation index system of entrustable professional activities for psychiatric resident training doctors was con-structed,including 4 first-level indicators,17 second-level indicators and 68 third-level indicators.The weights of the first-level,second-level and third-level indicators were determined.Conclusion:The evaluation index system of en-trustable professional activities is comprehensive and systematic,which is suitable for clinical work and convenient for practical application.It could provide quantitative standards for the assessment of psychiatric residents and pro-mote the improvement of training quality.

OBJECTIVETo evaluate the effect of subgingival scaling/root planning (SRP) and occlusal adjustment on clinical and occlusal parameters in teeth with chronic periodontitis and secondary occlusal trauma.

METHODSEighteen patients with chronic periodontitis and occlusal trauma were included and randomly divided into group A and group B. On day 0, group A was treated by full-mouth subgingival scaling and root planning, and group B was treated by occlusal adjustment in occlusal trauma site. On day 28, group A was treated by occlusal adjustment in occlusal trauma site, and group B was treated by full-mouth subgingival scaling and root planning. Probing depth (PD), attachment loss (AL), bleeding index (BI) were evaluated on 0, 28 and 56 d, and the occlusal time (OT) and the percentage of occlusal force were evaluated on 0, 28 and 56 d in occlusal trauma site. The data was statistically analyzed.

RESULTSIn baseline, the PD[(4.42 ± 1.41) mm vs (4.36 ± 1.38) mm], AL [(2.75 ± 1.32) mm vs (2.63 ± 1.37) mm] and BI [(2.20 ± 0.81) vs (2.24 ± 0.89)] of the full-mouth showed no significant difference between the two groups (P > 0.05). There was no significant difference in PD [(5.21 ± 1.21) mm vs (5.08 ± 1.12) mm], AL [(4.94 ± 1.47) mm vs (4.89 ± 1.32) mm], BI [(2.61 ± 0.92) vs 2.50 ± 0.79)], OT [(1.29 ± 0.39) s vs (1.34 ± 0.35) s] and the percentage of occlusal force [(6.8 ± 2.1)% vs (7.4 ± 1.7)%] in occlusal trauma site between the two groups(P > 0.05). After SRP therapy, the PD,AL,BI and OT were significantly decreased (P < 0.05).The clinical parameters exhibited no significant difference after only occlusal adjustment(P > 0.05).On 56 d, the reduction in clinical parameters was not significantly different between the two groups(P > 0.05),however the reduction of OT and the change of the percentage of occlusal force in group A [(0.85 ± 0.41) s, (2.2 ± 2.2)%] were more significant than those in group B [(0.70 ± 0.38) s; (1.5 ± 1.6)%] (P < 0.05). After occlusal adjustment, the increase of OT in group A [(0.21 ± 0.11) s] was lower than that in group B [(0.67 ± 0.37) s]through the 28-day observation period (P < 0.05).

CONCLUSIONSOcclusal adjustment alone is inadequate for control and management of periodontitis.SRP therapy can eliminate the inflammation and decrease the OT of tooth with occlusal trauma.The combination of SRP and occlusal adjustment may achieve more stable results.

Adult ; Aged ; Bite Force ; Chronic Periodontitis ; physiopathology ; therapy ; Dental Occlusion, Traumatic ; physiopathology ; therapy ; Dental Scaling ; Female ; Humans ; Male ; Middle Aged ; Occlusal Adjustment ; Periodontal Attachment Loss ; therapy ; Periodontal Index ; Root Planing