Chun-ting Lu

Antigen-extracted xenogeneic cancellous bone graft with recombinant human bone morphogenetic protein-2 enhances bone regeneration in repair of mandibular defect in rabbits

The effects of a large‐piece of xenogeneic bone that was separated from healthy pigs as a scaffold for the repair of a mandibular defect was investigated, and the applicability of antigen‐extracted xenogeneic cancellous bone (AXCB) soaked with recombinant human bone morphogenetic protein‐2 (rhBMP‐2) in bone defect repair was assessed. Mandibular defects were created in 48 New Zealand rabbits, and the animals were randomly divided into four groups, in which the mandibular defects were grafted with AXCB, AXCB soaked with rhBMP‐2, and autograft bone, or left blank. An equal number of animals from each group were classified into three time points (4, 8, and 12 weeks) after surgery for gross pathological observation, hematoxylin and eosin (H and E) staining, radiographic examination, and bone density measurement. H and E staining revealed that the area percentage of bone regeneration in the group of the AXCB/rhBMP‐2 graft was 27.72 ± 4.68, 53.90 ± 21.92, and 77.35 ± 9.83 at 4 weeks, 8 weeks, and 12 weeks, respectively. These results were better than those of the autogenous bone graft, suggesting that the group of the AXCB/rhBMP‐2 graft achieved a good osteogenic effect. With regard to the AXCB graft without rhBMP‐2, the area percentage of bone regeneration was only 14.03 ± 5.02, 28.49 ± 11.35, and 53.90 ± 21.92. Therefore, the osteogenic effect of the AXCB/rhBMP‐2 graft was demonstrated to have the best effect. In the group of the AXCB/rhBMP‐2 graft, the area percentage of bone regeneration increased, and the implanted materials were gradually degraded and replaced by autogenous bone regeneration over time. We conclude that the AXCB graft soaked with rhBMP‐2 showed good osteogenic effect in the repair of bone defects and good biocompatibility. AXCB serves as a good carrier of rhBMP‐2, which promotes bone formation.

Blood glucose and insulin and correlation of SLC25A13 mutations with biochemical changes in NICCD patients

Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is a hereditary metabolic disease arising from biallelic mutations of SLC25A13. This study aimed to explore the characteristics of fasting blood glucose (FBG), fasting insulin (FINS) and C-peptide (C-P) levels in NICCD infants, analyze their SLC25A13 genetic mutations and further discuss the correlation between SLC25A13 genetic mutations and biochemical changes. Seventy-two cases of infants with cholestasis disease were gathered. Among them, 36 cases with NICCD diagnosis were case group. Meanwhile, 36 cases with unknown etiology but excluded NICCD were control group. FBG, FINS, C-P, ALT, AST, GGT, ALP, TG, HDL-C, LDL-C and Non-HDL-C were collected from all subjects, and DNA was extracted from venous blood for SLC25A13 mutations detection. The incidence of hypoglycemia was 3% in NICCD group. There were no significant statistical difference of FBG, FINS and C-P between NICCD and INC groups (P > 0.05). ALT, LDL-C and Non-HDL-C levels in NICCD group were lower than the INC group, while SLC25A13 mutations were associated with the level of GGT (P < 0.05). Ten different SLC25A13 genetic mutations were detected, among which, 851del4, IVS16ins3kb, IVS6+5 G > A and 1638ins23 mutations made up 82% of all mutations. The incidence of hypoglycemia may be higher in small gestational age infants with NICCD. Low LDL-C may be one of the characteristics of dyslipidemia in NICCD infants. There was a correlation between SLC25A13 gene mutations distribution and the GGT level, but the meaning of this finding remains to be further in-depth study. Impact statement This study aims to compare FBG, FINS, C-P, other biochemical and clinical manifestations between NICCD and non-NICCD infants, and discuss differential diagnosis of NICCD and INC beyond the genetic analysis. And investigate the correlation between SLC25A13 genetic mutations and biochemical changes. This work presented that incidence of hypoglycemia may be higher in small gestational age infants with NICCD. Low LDL-C may be one of the characteristics of dyslipidemia in NICCD infants. There was a correlation between SLC25A13 gene mutations distribution and the GGT level.

An Effective Teaching Method to Enhance History-Taking Skills for Chinese Medical Students

History taking is an extremely important skill for medical students to master. In China, medical students usually have opportunities to practise this skill on real patients after they have learned diagnostics and basic relevant theoretical knowledge. Today, however, several factors, such as increased enrolment of medical students and the need to ensure patient safety in avoiding stressful doctor-patient relationships may increase both the difficulty and the importance for medical students to develop this skill. In view of these situations, the aim of this study was to introduce one specific teaching method, i.e., role-play activity, in order to help medical students cultivate and practise history-taking and related skills. 52 third-year medical students were divided into two groups. Students in observation group received role-play activity training before interviewing with real patients. Students in control group were taught by traditional methods without the new method intervention. The teaching effects of role-play activities were evaluated via medical records, tests of history taking and theoretical exams, and questionnaire for the observation group. The scores of seven medical case records for each student in the observation group were analysed and were found to be higher than those in the control group. These results showed no significant differences between the two groups in the first and second interview records with real patients in the hospital, but statistically significant differences were found from the third time. The scores on history-taking tests with a standardized patient (SP) were higher in the observation group than in the control group. No significant difference was found between the two groups in their theory exam scores. Results indicated that role-play activity is an effective method for medical students to improve their history-taking skills.

The National Clinical Skills Competition Promotes the Construction of a Comprehensive Training Program for Chinese Medical Students.

To explore an efficient training program based on an analysis in organizing seven sessions for the National Clinical Skills Competition in China. Each year, 6-12 excellent medical students of our university are selected as an observation team. Comparisons of the teaching characteristics were performed in this study. An optimal curriculum implementation, specific clinical teaching scenarios and evaluation methods were gradually obtained and improved. Teaching effects were satisfactory. Among seven sessions, the eighth session was the best. Curriculum construction and training team building are formed synchronously through this National Clinical Skills Competition. Clinical skills training should be designed and evaluated effectively in order to increase the comprehensive capacities of medical students.

Ectopic osteogenesis effect of antigen-extracted xenogeneic cancellous bone graft with chitosan/rhBMP-2/bFGF sequential sustained-release nanocapsules:

To explore the ectopic osteogenesis effect of sequential sustained release application of recombinant human bone morphogenic protein-2 (rhBMP-2) and basic fibroblast growth factor (bFGF). Antigen-extracted xenogeneic cancellous bone coupled with growth factor-loaded chitosan nanocapsules were implanted in rats in intramuscular site in accordance with the following experimental pattern: group A: simultaneous burst release of rhBMP-2 and bFGF; group B: simultaneous sustained release of rhBMP-2 and bFGF; group C: preferential burst release of rhBMP-2, then sustained release of bFGF; group D: preferential burst release of bFGF, then sustained release of rhBMP-2; group E: sustained release of rhBMP-2 alone; group F: sustained release of bFGF alone, blank control group G: antigen-extracted xenogeneic cancellous bone graft only; negative control group H: not filled with anything. Specimens were obtained after executing the animals at 2 and 4 weeks for general observation and weighing, calcium content detection, micro-CT scanning and bone parameter measurement analysis, H&E staining, ALP staining and CD34 staining. The materials weight of A-2, B-2, C-2, A-4, B-4, C-4, D-4 and E-4 were significantly higher than that of preoperative materials (P < 0.05). The concentration of calcium of group B-4 was the highest (414.7 ± 12.03 mg/dl). Micro-CT scanning and bone parameter measurement analysis showed that the values of bone mineral density and trabecular thickness of group A, B, D, E at 4 weeks were both higher than the ones at 2 weeks (P < 0.05), and both the bone mineral density (367.52 ± 11.64 mg/cc) and the trabecular thickness (126.17 ± 11.36 μm) of group B-4 were the highest. H&E staining showed that a large region of calcified cartilage and haemopoietic tissues were newly formed, especially in group B-4. ALP staining and CD34 staining showed the most positive expression region in group B-4. Therefore, we conclude that simultaneous sustained release of rhBMP-2 and bFGF is the ideal way to release drug, and has better inducement of antigen-extracted xenogeneic cancellous bone graft.

Cultivation of periodontal tissue cell sheet by a new way for cell sheet engineering

We incorporate the idea by Akashi et al. which utilize disulfide bonds in forming the porous hydrogel. We further develop a system using γ-PGA as scaffold and disulfide bonds cleavage as the critical point of cell sheet detach system. Cytotoxicity tests showed good biocompatibility of the matrix PVDF membranes. Finally, the cell sheet detachment was successfully performed by adding cysteine after DPSC (Dental Pulp Stem Cell) or PDLSC (Periodontal Ligament Stem Cell) cultured for one week.

Activation of FAK promotes ERK-mediated osteogenesis for tensile force-subjected periodontal ligament cell

The exact mechanism of translate mechanical signals of the focal adhesion kinase (FAK) into osteoblast differentiation power. PDL cells and MG63 cells were under-100 kPa for different periods. The tension force of focal adhesion kinase (FAK) phosphorylation increases rapidly and upregulation of osteogenic protein expression in periodontal ligament cells, but not in MG63 cells with FAK antisense oligonucleotides decreased ALP and Osteocalcin (OC) secretion in cells transfected with PDL. These findings suggest that the tension of the activation of the FAK pathway in periodontal ligament cells, and regulate immune cytokines and regulation of bone morphogenetic protein.

Hepatic cirrhosis in a citrin-deficient infant

A 10-month-old female infant was referred to our hospital due to prolonged jaundice over 9 months and fever of 4 days. Physical examination revealed enlargement of the liver and spleen, as well as ascites. Liver ultrasound indicated multiple firm nodules. Laboratory tests showed hyperbilirubinemia, hypoglycemia, hypoalbuminemia and coagulopathy. Increased citrulline and methionine were detected by MS-MS analysis of serum amino acids, while large quantity of 4-hydroxyphenylpyruvic and 4-hydroxyphenyllactic acid were detected by GC-MS analysis of urine sample. The diagnosis was hepatic cirrhosis, and Citrin Deficiency was suspected to be the initial etiology. The diagnosis was confirmed by High-frequency mutation screening and direct sequencing of SLC25A13 gene that revealed a compound heterozygote of IVS16ins3kb and c.495delA mutation. This study provided additional clinical evidence to challenge the traditionally-assumed benign prognosis of patients with Neonatal Intrahepatic Cholestatic Caused by Citrin Deficiency (NICCD).