Objective To evaluate the efficacy and safety of recombinant human brain natriuretic peptide (rh-BNP) combined with levosimendan on acute myocardial infarction complicated by heart failure.Methods Patients who suffered from anterior wall acute myocardial infarction (AMI) with heart failure (KillipⅡ ～ Ⅲ) within 12 to 24 hours after the onset of chest pain were randomized into two groups: the control group (n=30, receiving dobutamine and/or cedilanid) and the experimental group (n=30, receiving rh-BNP combined with levosimendan).The hemodynamics, parameters of laboratory tests and adverse events were observed before and after treatment.Results The experimental group showed that the respiratory rate (RR), heart rate (HR), systolic blood pressure (SBP), arterial blood gas oxygen saturation (SaO2), cardiac index (CI), extravascular lung water index (EVLWI) were significantly different between 2 h and sequential time points after treatment and pre-treatment (allP＜0.05).The control group showed that RR, HR, SaO2, CI, EVLWI were significantly different between 6 h and sequential time points after treatment and pre-treatment (P＜0.05 for all).There were significant differences in RR, HR, SBP, SaO2, CI, EVLWI at 2 h and 6 h after treatment between the two groups (P＜0.05 for all).Parameters of RR, HR, CI, EVLWI at 72 h after treatment had differences between the experimental group and controls.Patients in the experimental group presented larger urine volume, lower level of plasma NT-pro BNP, higher left ventricular ejection fraction (LVEF) and shorter length of stay in CCU as compared with patients in the control group (P＜0.05 for all).In adverse events monitoring in hepatic parameters, electrolyte level and coagulation function before and after treatment, there was no significant difference between the two groups.Conclusions Compared with the conventional treatment, the combination therapy with rh-BNP and levosimendon can improve the hemodynamics, increase the urine volume, decrease the level of plasma NT-proBNP and elevate LVEF significantly, so as to improve the clinical symptoms and shorten the hospital stay in patients with acute myocardial infarction complicated by heart failure.

Objective To investigate the role of vitamin D in the synthesis and degradation of aggrecan in rat articular chondrocytes at cellular level. Methods Rat articular chondrocytes were stimulated by IL-1α, IL-1β and TNF-α, respectively. Normal and inflammatory chondrocytes were treated with different doses of vitamin D, respectively. CCK8, Flow cytometry, real time-PCR and western blot analysis were used to examine the proliferation activity and apoptosis level of chondrocytes, and the expression of aggrecan, ADAMTS-4 and ADAMTS-5 at both mRNA and protein levels. Results IL-1α,IL-1β and TNF-α significantly decreased the proliferation activity and increased the apoptosis level of the chondrocytes. Furthermore, IL-1α, IL-1β and TNF-α significantly decreased the expression of aggrecan, and increased the expressions of ADAMTS-4 and ADAMTS-5 at both mRNA and protein levels in the chondrocytes. 1α,25 (OH)2D3supplementation significantly increased the proliferation activity and decreased the apoptosis level of chondrocytes stimulated by IL-1α, IL-1β and TNF-α in a dose-dependent manner, but not affected the normal chondrocytes. Meanwhile, 1α,25(OH)2D3also significantly increased the expression of aggrecan, and decreased the expressions of ADAMTS-4 and ADAMTS-5 at both mRNA and protein levels in the chondrocytes under inflammatory conditions. Conclusions Vitamin D may promote the anabolism of aggrecan and inhibit aggrecanase activity in chondrocytes under inflammatory conditions, which may impact overall protection for articular cartilage.

Objective To study fluid flow within alveolar bone under orthodontic and occlusal loading, so as to provide references for understanding the regulatory mechanism of bone remodeling during orthodontics. Methods An animal model for orthodontic tooth movement on rats was first constructed. The finite element model of tooth-periodontal ligament-alveolar bone was established based on micro-CT images and the strain field in alveolar bone under orthodontic or constant occlusal loading was analyzed. Then finite element model of alveolar bone was constructed from the bone near the cervical margin or apical root of mesial root. The fluid flow in this model under orthodontic and cyclic occlusal loading was further predicted by using fluid-solid coupling numerical simulation. Results The fluid velocity within alveolar bone cavity mainly distributed at 0-10 μm/s, and the fluid shear stress (FSS) was mainly distributed at 0-10 Pa. FSS on the surface of alveolar bone near the apical root was higher than that close to the cervical margin. Conclusions FSS at different levels could be produced at different location within alveolar bone cavity under orthodontic and cyclic occlusal loading, which might further activate biological response of bone cells on the surface of trabeculae and finally regulate the remodeling of alveolar bone and orthodontic movement of tooth. The results provide theoretical guidance for the clinical treatment of orthodontics.

Fluid shear stress (FSS) caused by interstitial fluid flow within trabecular bone cavities under mechanical loading is the key factor of stimulating biological response of bone cells. Therefore, to investigate the FSS distribution within cancellous bone is important for understanding the transduction process of mechanical forces within alveolar bone and the regulatory mechanism at cell level during tooth development and orthodontics. In the present study, the orthodontic tooth movement experiment on rats was first performed. Finite element model of tooth-periodontal ligament-alveolar bone based on micro computed tomography (micro-CT) images was established and the strain field in alveolar bone was analyzed. An ideal model was constructed mimicking the porous structure of actual rat alveolar bone. Fluid flow in bone was predicted by using fluid-solid coupling numerical simulation. Dynamic occlusal loading with orthodontic tension loading or compression loading was applied on the ideal model. The results showed that FSS on the surface of the trabeculae along occlusal direction was higher than that along perpendicular to occlusal direction, and orthodontic force has little effect on FSS within alveolar bone. This study suggests that the orientation of occlusal loading can be changed clinically by adjusting the shape of occlusal surface, then FSS with different level could be produced on trabecular surface, which further activates the biological response of bone cells and finally regulates the remodeling of alveolar bone.

The important function of the endplate is to transmit stress and supply nutrition. Endplate degeneration might induce or promote degeneration of the intervertebral disc, causing a series of spine diseases that seriously impair people’s health and life quality. Endplate chondrocytes can respond to mechanical stimulation, which is an important factor affecting endplate degeneration. Inappropriate mechanical stimulation will accelerate endplate degeneration. This review summarized the effects of mechanical stimulation on vertebral endplate chondrocyte apoptosis, synthesis inhibition, calcification, and extracellular matrix degradation. The endplate degeneration induced by mechanical stimulation is regulated by a complex network of signal pathways composed of various signal transduction factors. The signal pathways involved in this review included NF-κB, Wnt, Hedgehog, MAPK, RhoA/Rock-1, AKT/mTOR, TGF-β signaling pathway and miRNA related signals. The interconnection of these pathways was highlighted and summarized. Multiple signaling pathways work together to regulate endplate chondrocyte metabolism, which ultimately leads to the endplate degeneration. This review might shed light on early diagnosis and precise treatment of cartilage endplate degeneration.