Objective To explore the expression changes of HSP90αin cardiac muscles and survival rates in rats by using the different fluids to resuscitate the severs hemorrhagic shocked rats ,and provide reference for the clinical treatment of hemorrhagic shock with different resuscitation fluids .Methods Uncontrolled hemorrhagic shock rats model was established ,using lactic acid salinger liquid ,poly peptide injection gelatin ,hypertonic sodium chloride dextran for fluid resuscitation respectively ,and then checked the HSP90αexpression changes and survival rates in rats .Results the expressions of HSP90αin myocardial tissue and the mortality in rats were different after using different resuscitation fluids in severe hemorrhagic shock rats ,difference was statistically significant(P<0 .05) .Conclusion the expression of HSP90α in cardiac muscles of rats could be induced by severe hemorrhagic shock ,the HSP90αexpressed differently and regularly after using different resuscitating fluids ,it implied that the HSP90α played an important role in the hemorrhagic rats cardiac as a regulating fator .

To explore novel non-opioid analgesic agents, 16 compounds were synthesized and their structures were confirmed by 1H NMR and HR-MS. YX0611-1 was treated as the leading compound. The results of mice writhing model and hot plate model showed that compounds 2, 7, 8, 9, 11 and 15 had obvious analgesic activities in vivo. The test of affinity to mu, delta, kappa receptor displayed that active compounds didn't act on opioid receptor. The results of preliminary toxicity and pharmacokinetic tests showed that compound 7 had better safety and pharmacokinetic properties than that of YX0611-1, and it deserved further development.

Objective:To explore the blocking effect of temporary epiphysiodesis technique with "8"-plate in the treatment of leg length discrepancy (LLD) in children.Methods:From January 2013 to July 2020, 49 children (27 males and 22 females) with leg length discrepancy treated with "8"-plate in Pediatric Orthopedics Department of Beijing Jishuitan hospital were analyzed retrospectively. The average age at the time of surgery was 8.8±2.6 years (ranging from 3.8 to 13.1 years). The length difference between femur and tibia was measured before operation on full-length X-ray films of lower limbs, and the "8"-plate was placed on both medial and lateral sides of the distal femur and/or the proximal tibia. During the follow-up, the shape of epiphyseal plate and internal fixation change were evaluated on X-ray films of the knee joint, and the length difference before and after the operation was compared to evaluate the blocking effect. The blocking rate was compared according to the following conditions: the blocking position (femur, tibia), classification of LLD (constant or increasing), screw diameter (3.5 mm or 4.5 mm) and the age at operation (≥8 or <8 years).Results:49 patients were successfully operated. The follow-up time was 39.6±18.5 months (range 16-91 months) with the fixing time of 24.3±11.8 months (range 7-66 months). A total of 76 independent data of single bone were obtained. The correction range was 8.6±6.4 mm (range -8-37 mm). The correction rate was 0.35±0.31 mm/month. The correction rate of 52 femurs was 0.41±0.32 mm/month, which was significant higher than that of 24 tibias with 0.20±0.14mm/month ( t=5.323, P=0.008). The correction rate of the constant group with 0.54±0.32 mm/month was obviously better than the increasing group with 0.26±0.21 mm/month ( t=7.362, P=0.001). The average correction rate of 4.5 mm diameter screw group was 0.46±0.23 mm/month, which was significantly better than that of 3.5 mm diameter screw group with 0.26±0.24 mm/month ( t=3.467, P=0.022). The correction rate in the group of <8 years old was 0.32±0.25 mm/month, which was not significantly different from that in the group of ≥8 years old with 0.37±0.31 mm/month ( t=1.026, P=0.548). Conclusion:The blocking effect of "8" -plate temporary epiphysiodesis technique in the treatment of leg length discrepancy was related to the LLD classification and blocking position. Distal femoral block was better than proximal tibia block. Block effect of patients with constant unequal distance between lower limbs was better than that of patients with increased distance. 4.5 mm diameter screw was better than 3.5mm. Because the blocking effect was slow, early treatment and a firm stick to indications was of great importance.

Anoctamin 1 (ANO1) is a kind of calcium-activated chloride channel involved in nerve depolarization. ANO1 inhibitors display significant analgesic activity by the local peripheral and intrathecal administration. In this study, several thiophenecarboxylic acid and benzoic acid derivatives were identified as novel ANO1 inhibitors through the shape-based virtual screening, among which the 4-arylthiophene-3-carboxylic acid analogues with the best ANO1 inhibitory activity were designed, synthesized and compound

Dopamine D₃ receptor (D₃R) is implicated in multiple psychotic symptoms. Increasing the D₃R selectivity over dopamine D₂ receptor (D₂R) would facilitate the antipsychotic treatments. Herein, novel carbazole and tetrahydro-carboline derivatives were reported as D₃R selective ligands. Through a structure-based virtual screen, ZLG-25 (D₃R K_i = 685 nmol/L; D₂R K_i > 10,000 nmol/L) was identified as a novel D₃R selective bitopic ligand with a carbazole scaffold. Scaffolds hopping led to the discovery of novel D₃R-selective analogs with tetrahydro-β-carboline or tetrahydro-γ-carboline core. Further functional studies showed that most derivatives acted as hD₃R-selective antagonists. Several lead compounds could dose-dependently inhibit the MK-801-induced hyperactivity. Additional investigation revealed that 23j and 36b could decrease the apomorphine-induced climbing without cataleptic reaction. Furthermore, 36b demonstrated unusual antidepressant-like activity in the forced swimming tests and the tail suspension tests, and alleviated the MK-801-induced disruption of novel object recognition in mice. Additionally, preliminary studies confirmed the favorable PK/PD profiles, no weight gain and limited serum prolactin levels in mice. These results revealed that 36b provided potential opportunities to new antipsychotic drugs with the multiple antipsychotic-like properties.