Search

The regulatory guidelines for the research and development of paediatric drugs are still evolving in China. The formulation of the guidelines started from learning and borrowing existing experience, and gradually changed to the exploration and improvement of local guidelines, which was not only in line with international standards but also had breakthroughs, innovations and Chinese characteristics. In this paper, the current setting of paediatric drug research and development in China and corresponding technical guidelines have been introduced from regulatory perspectives, and the accessibility of further improvement in regulatory strategies has also been discussed.

To investigate the expression of costimulatory molecule Tim3 and its subsets on NK cells in patients with acute myeloid leukemia.30 patients with acute myeloid leukemia treated in our hospital from August 2016 to August 2018 were randomly selected as the AML group, and 30 healthy persons in our hospital during the same period were randomly selected as the control group. The expression levels of CD56The expression levels of CD56The expression of costimulatory molecule Tim3 in NK cells and its subsets of patients with acute myeloid leukemia is down-regulated.共刺激分子Tim3在急性髓系白血病患者NK细胞及其亚群上的表达分析.分析共刺激分子Tim3在急性髓系白血病（AML）患者NK细胞及其亚群上的表达.回顾性研究2016年8月至2018年8月本院收治的30例急性髓系白血病患者（AML组），另选取同期本院健康体检人员30例作为对照组，统计分析2组人员的外周血CD56AML组患者的外周血CD56共刺激分子Tim3在AML患者NK细胞及其亚群上的表达下调.

Based on the first-principles calculations, the stable structures of FexM1-x (M = Y, La) binary alloy have been determined according to the formation enthalpy, and the calculated binding energy of hydrides as a function of chemical potential show that the YFe2H4.5 is stable. The thermodynamic stabilities of target alloys and hydrides at various temperatures have further been confirmed using the quasi harmonic approximation in lattice vibration theory. The nudged elastic band method (NEB) is used to investigate the diffusion of hydrogen atoms at different interstitials. The charge density distribution of YFe2 and YFe2H5 has been analyzed to demonstrate the structural stability and the dehydrogenation process. The elastic modulus of YFe2, YFe2H5, LaFe2 and LaFe2H5 will decrease as the temperature increases, with a weaker anisotropy in the Y–Fe system than that in the La–Fe system.

Protein-protein interactions (PPIs) as drug targets have been gaining growing interest, though developing drug-like small molecule PPI inhibitors remains challenging. Peptide PPI inhibitors, which can provide informative data on the PPI interface, are good starting points to develop small molecule modulators. Computational methods combining molecular dynamics simulations and binding energy calculations could give both the structural and the energetic perspective of peptide PPI inhibitors. Herein, we set up a computational workflow to investigate Keap1-Nrf2 peptide PPI inhibitors and predict the activity of novel sequences. Furthermore, we applied this method to investigate p62 peptides as PPI inhibitors of Keap1-Nrf2 and explored the activity change induced by the phosphorylation of serine. Our results showed that because of the unfavorable solvation effects, the binding affinity of the phosphorylated p62 peptide is lower than the Nrf2 ETGE peptide. Our research results not only provide a useful method to investigate the Keap1-Nrf2 peptide inhibitors, but also give a good example to show how to incorporate computational methods into the study of peptide PPI inhibitors. Besides, applying this method to p62 peptides provides a detailed explanation for the expression of cytoprotective Nrf2 targets induced by p62 phosphorylation, which may benefit the further study of the crosstalk between the Keap1-Nrf2 pathway and p62-mediated selective autophagy.

Combining experimental XRD phase analysis and melting-annealing temperature with the high-through first-principles calculation, the structural stability, mechanical strength and electronic properties of V-Fe-Zr and Sc-Fe-Y quasi-binary alloys have been systematically investigated. The calculation of formation enthalpy and the free energy show that VxFe2(1-x)Zr alloy has a completely ordered solid solution at low temperature, while ScxY1-xFe2 alloy needs to be annealed at a high temperature up to 700 °C to reach disordered fusion state. The bond energy model can accurately predict the total energy and bulk modulus of the target alloy structure at each substitution concentration, whose numerical differences per atom between the calculated results and predicted ones by bond energy model (BEM) are less than 1 meV and 0.2 GPa, respectively. The elastic modulus obtained by fitting within Birch-Murnaghan equation and calculating from elastic constants has good consistency.

Activation of Nrf2 by directly inhibiting the Keap1–Nrf2 Protein–Protein Interaction (PPI) has gained research interest with regard to developing novel agents for treating inflammatory related diseases. In this study, computational methods were used to guide the rational activity improvement of peptide Keap1–Nrf2 inhibitors and to explore the Keap1 binding cavity. Terminal hydrophobic residues and Tyr residue replacements were introduced into the novel peptides. The experimental values of these peptides further confirmed the potential binding sites explored by the MD simulation. Finally, the most promising, peptide 5 with an intracyclic conformation showed a Kd value of 2.8 nM when binding to Keap1 and an IC50 value of 9.4 nM in the Keap1–Nrf2 PPI fluorescence polarization assay. It proved that the active conformation locking strategy is quite useful in Keap1–Nrf2 PPI inhibitor design. It also provided a useful probe to investigate the Keap1–Nrf2 PPI system.

Ulcerative colitis (UC) is a chronic relapsing-remitting form of inflammatory bowel disease (IBD) that increases the risk of colorectal cancer, the third most common malignancy in humans. Oxidative stress is a risk factor for the development of UC. The Keap1-Nrf2-ARE pathway is one of the most important defensive mechanisms against oxidative and/or electrophilic stresses. In this study, we identified CPUY192018 as a potent small-molecule inhibitor of the Keap1-Nrf2 PPI, investigated the cyto-protective effects of CPUY192018 on the NCM460 colonic cells and evaluated whether treatment with the inhibitor of the Keap1-Nrf2 PPI exerts protection on an established experimental model of UC induced by dextran sodium sulfate (DSS). Our study clearly demonstrated that CPUY192018 had a cytoprotective effect against DSS in both NCM460 cells and mouse colon via the activation of Nrf2 signaling. These results suggested that activation of Nrf2 by directly inhibiting the Keap1-Nrf2 PPI may be beneficial as a treatment for UC.

To evaluate the usefulness of custom-made key-key attachment in restoration of maxillofacial defect.Using key-key attachment, facial prostheses and intraoral prostheses were combined to restore dentition, maxilla and right facial defects in a female patient.Good retention of maxillofacial prostheses and intraoral prostheses were obtained. The appearance of the patient was remarkably improved. The function of mastication was improved.Good result can be obtained by using custom-made key-key attachment in restoration of complex maxillofacial defect. Supported by Shanghai Leading Academic Discipline Project(Grant No.T0202).

Prosthetic rehabilitation with stud structure to sectional complete denture for a patient with microstomia was done and the treatment result was evaluated.A sectional impression tray technique was used. And a custom-made palatal hinge mechanism with stud structure on the left and right side of the upper complete denture along the middle line were also designed and fabricated. Half metal abutment was fabricated on the left and right side of the denture on the position of the upper central incisor, and a PFM was made according to the metal abutment. After the sectional upper complete denture was inserted, the PFM was set to connect the sectional denture as a whole and provide stability.The sectional upper complete denture was successfully and easily inserted and provided adequate function in the patient's mouth.Application of stud structure to sectional upper complete denture for patient with microstomia is feasible.

To evaluate the long-term clinical results of porcelain fused to metal prostheses.Since January 1995, 920 porcelain fused to metal prostheses were fabricated. The long-term outcome were evaluated according to the condition of the prosthese, abutment and the periodontal tissue in the respects of successful rate and causes of failure.74 patients were found to be during the follow up period, including 36 anterior crowns (46 units), 18 posterior crowns (22 units), 12 percentage of anterior bridges and 8 posterior bridges. The overall failure rate was 8.04%, 4.84% for crown, 8.77% for bridge. The failed prostheses was 5.39%.Porcelain fused to metal prostheses is an ideal method for restoration. The standard process both for the clinician and the technician must be obeyed to improve the success rate.

To evaluate the masticatory efficiency and phonetics in patients with cleft lip and palate before and after double dentition denture treatment, and determine the results of the treatment.6 patients who had cleft lip and palate with defect smaller than 1 cm x 1 cm or submucous cleft palate were selected to undergo double dentition denture treatment. Two kinds of base design were used. One was with artificial teeth and buccal base only. The other was with artificial teeth and base on both the buccal and palatal sides. Masticatory efficiency and phonetics effect were tested before and immediately after treatment and 1 month after treatment. The data were analyzed using SPSS11.0 software package for paired t test.There was statistically significant difference in masticatory efficiency, before and immediately after treatment and 1 month after treatment (P0.01). As for phonetics , there was statistically significant difference on F2 and F3 before and immediately after treatment as well as 1 month after treatment (P0.05). While there were no statistically significant difference both on masticatory efficiency and phonetics between the two kinds of design.Both the two kinds of treatment can improve the masticatory efficiency and phonetics effectively. It is not necessary to use the palatal base when the defect is smaller than 1 cm x 1 cm or submucous cleft palate present.

Evaluation of the outcomes in 15 patients with unilateral maxillary defect before and after maxillofacial obturator prosthesis.15 patients with unilateral maxillary defect were included in this study, who received obturator prosthesis for maxillary rehabilitation. The pronunciation of the examined phonetics such as /a/, /o/, /e/, /i/, /u/ were transferred into CSL4400 before and after treatment. The mean value of the first, second, third formant were measured. Paired t test of SPSS11.0 was used for statistical analysis.There was statistically significant difference on F2 and F3 before and after treatment (P0.05). After treatment the value of F3 was increased significantly.The soft palate was reconstructed after obturator treatment. The space between the nasal and oral cavity was sealed,through which a similar normal oral cavity was obtained. Except F1, F2 and F3 of all the vowels changed after treatment. Maxillofacial prosthesis can improve the speech function of patients with unilateral maxillary defect effectively.

To evaluate the application of precise attachment in restoration of complicated maxillofacial defect.A framework with bar-clip and stud attachment was designed and fabricated. Maxillofacial prosthesis with this framework was applied to treat a patient with defects of nose, entire upper lip and the corresponding maxillofacial areas. The retention force was tested with Universal Testing Device.After treatment, the patient got a better appearance, normal function of mastication and clear pronunciation. The dislodgement test showed the retention force was 40N.Application of precise attachment in complicated maxillofacial defects can get satisfactory result.

To evaluate the clinic results of maxillofacial prosthetic treatment for unilateral maxillary defect.Masticatory efficiency was tested before and after maxillofacial prosthetic treatment for unilateral maxillary defect.There was significant difference between one week, one month, three months after treatment and before treatment(F = 0.635, P = 0.002). Masticatory efficiency was increased by 59.98% after one month.Maxillofacial prosthetic treatment can significantly increase the masticatory efficiency of unilateral maxillary defect. It remains stable one month later.