Objective To explore the effects of Tepp-46, a pyruvate kinase M2 (PKM2) agonist, on the skin fibrosis of patients with systemic scleroderma (SSc) and its therapeutic effect on the SSc mouse models. Methods Full-thickness skin tissues of SSc patients and healthy controls were taken, and the expression levels of PKM2 and α-smooth muscle actin (α-SMA) were detected using immunohistochemical staining. The skin primary fibroblasts were isolated from the tissues, and the PKM2 protein expression was detected using Western blotting. SSc fibroblasts were stimulated with Tepp-46 of different concentrations, and Western blotting was used to measure the expression of PKM2, collagen type Ⅰα1 (ColⅠα1) and α-SMA protein after the stimulation. The C57BL/6 mice were randomly divided into three groups: control group, bleomycin (BLM) group and Tepp-46 group. BLM was injected subcutaneously to establish the SSc mouse model, at the same time, Tepp-46 treatment initiated in the Tepp-46 group. At 21 d after modeling, the mice were executed and their skins were taken. HE staining and Masson staining were used to analyze morphological changes of the skin. The immunohistochemical staining was used to examine the expression of PKM2 and α-SMA protein in the mouse skin. Western blotting was used to analyze the expression of ColⅠα1 and PKM2 in the mouse skin. Results Compared with the healthy controls, α-SMA protein expression in the dermis of SSc patients was higher, and PKM2 protein expression in the epidermis and dermis of SSc patients increased (P＜0.000 1). PKM2 protein expression in primary fibroblasts of SSc skin was higher than that of healthy controls (P＜0.01); after Tepp-46 stimulation, the levels of ColⅠα1 and α-SMA in SSc fibroblasts decreased (P＜0.01), but PKM2 protein was not affected. In the mice, HE and Masson stainings showed that compared with BLM group, the pathological changes of skin were alleviated in the Tepp-46 group. The immunohistochemical staining results showed the levels of PKM2 and α-SMA in the skin of Tepp-46 group were lower than those of the BLM group (P＜0.000 1). Western blotting results showed the level of ColⅠα1 in the Tepp-46 group was lower than that in the BLM group (P＜0.001). Conclusions The expression of PKM2 protein in SSc skin tissue and primary fibroblasts is up-regulated, and PKM2 agonist Tepp-46 can inhibit SSc skin fibrosis.

Objective: To explore the molecular mechanism of Taoren-Honghua herb pair (THP) on syndrome of bloodstasis based on the network pharmacology. Methods: We collected THP's compounds from traditional Chinese Medicinedatabases and input them into Pharm Mapper to get their potential targets, and collected the known targets of compoundsby Scifinder. Then we did KEGG-pathway analysis by DAVID database. Finally draw and analyze the network byCytoscape by information above. Results: Seventeen compounds of THP acquired 74 known targets, which was associatedwith four modules: improving the hemodynamics, anticoagulation, anti-inflammation, regulating apoptosis andproliferation. We also got 317 potential targets through PharmMapper and got 128 signaling pathway through pathwayenrichment including 39 disease-related pathways, 25 endocrine-related pathways, 11 immune-related pathways and soon. Conclusion: The four modules of the known target are exactly related to the four characteristics of the syndrome ofblood stasis. The potential targets and the 128 signal pathways involve a variety of pathophysiological processes of thesyndrome of blood stasis. These reflect the molecular mechanism of THP intervention in the syndrome of blood stasis

Objective: To investigate the morphology and position changes of displaced disk with reduction after treatment by modified Twin-block. Methods : 19 patients were diagnosed as displaced disk with reduction and they were treated with modified Twin-block from July 2015 to June 2016. 28 temporomandibular joints (TMJ) of these patients were included in the analysis. The disk length, disk-condylar distance, and disk-condylar angle were measured with MRI before and after treatment. Paired t-test was used. Disk morphology before and after treatment was also documented and analyzed by Wilcoxon signed rank test. The statistical significance was set at P<0.01. Results : 28 TMJ disks were anteriorly displaced with reduction. 24 of them were repositioned while the other 4 were still anteriorly positioned after treatment. The disk length was increased significantly (P<0.01) while the disk-condylar distance and disk-condylar angle were decreased significantly after treatment (P<0.01). The disk morphology as hemiconvex (16) and bi planar (9) were the majority before treatment, while biconcave (16) and biplanar (10) were changed to the larger part after treatment. There was improvement on the disk deformation with a statistical significance (P<0.01). Larger disk-condylar distance, disk-condylar angle and severer deformation of disks were observed in the 4 disks without reposition. Conclusion Modified twin-block is an effective appliance for disk displacement with reduction by repositioning the disk and modifying the disk deformation. However the effect is not good for disks with severer deformation and displacement. Further studies with larger sample and stratified group are still needed.

Objective: To evaluate the potential dose influence to organs at risk (OARs) and targets of adaptive radiotherapy (ART) for non-small cell lung cancer (NSCLC). Methods:Twice positional CT images of 12 patients with locally advanced NSCLC were captured during radio-(n=3) or radio-chemotherapy (n=9) for ART simulation. The twice positional scanningplan was fused using MIM software. The variation of irradiation doses for the lung, heart, and spinal cord was evaluated, and the prescription doses for the targets were escalated. Results:Adaptive radiation enabled dose reduction by an average of 3.53%for lung V20 and by 2.55%for V30. The mean dose for the lung decreased by 2.11 Gy. The dose was reduced by an average of 4.17%for heart V30 and by 3.37%for V40. Meanwhile, the maximum dose for the spinal cord was reduced by 3.52 Gy on average. Lung sparing with ART enabled an iso-mean lung dose escalation of the Planning gross tumor target volume dose, which improved by an average of 1.25 Gy. Conclusion:The adap-tation of radiotherapy for continuous tumor shrinkage during the treatment course for NSCLC reduces doses to OARs, enables signifi-cant dose escalation, and has the potential to increase local control.