Tryptophan 2,3-dioxygnease 2 (TDO2) is specific for metabolizing tryptophan to kynurenine (KYN), which plays a critical role in mediating immune escape of cancer. Although accumulating evidence demonstrates that TDO2 overexpression is implicated in the development and progression of multiple cancers, its tumor-promoting role in esophageal squamous cell carcinoma (ESCC) remains unclear. Here, we observed that TDO2 was overexpressed in ESCC tissues and correlated significantly with lymph node metastasis, advanced clinical stage, and unfavorable prognosis. Functional experiments showed that TDO2 promoted tumor cell proliferation, migration, and colony formation, which could be prevented by inhibition of TDO2 and aryl hydrocarbon receptor (AHR). Further experimentation demonstrated that TDO2 could promote the tumor growth of KYSE150 tumor-bearing model, tumor burden of C57BL/6 mice with ESCC induced by 4-NQO, enhance the expression of phosphorylated AKT, with subsequent phosphorylation of GSK3

【Objective】 To study the application of electronic crossmatching(E-XM) based on Rh typing aimed at reducing the production of alloantibodies in blood recipients. 【Methods】 A total of 22 528 RhD positive patients, admitted to our hospital from Jan 1, 2018 to Mar 31, 2020, required the specific transfusion of leukocyte-depleted suspension red blood cells. Among which, 21 334 reached the priority level Ⅰ and Ⅱ by E-XM and were set as the control group, and 1 194 reached the priority level Ⅲ and were set as the experimental group. ABO and Rh (D, C, c, E and e antigens) blood group systems were serologically tested both in blood recipients and donors, and Rh phenotype database was established based on the blood transfusion management system. The incidence of irregular antibodies against the exposure of new antigens involved with RBC transfusions in the control group and the experimental group was compared. 【Results】 The proportion of antigen C and e was significantly higher than that of c and E. The frequency of DCCee and DCcEe were the highest, while that of Dccee and DCCEE were extremely low. 85.2% and 9.5% of the patients reached priority level Ⅰ and Ⅱ, respectively, and only 5.3% reached priority level Ⅲ. 6 patients(less than 0.001%) in the control group (n=21 334), developed Rh system alloantibodies after blood transfusion, and 24 patients(2.01%) in the experimental group (n=1194) developed Rh alloantibodies against the exposure of antigens after blood transfusion. There were significant differences between the experimental group and the control group (P<0.01). 【Conclusion】 The application of E-XM could minimize the incidence of Rh irregular antibodies after RBC transfusion in patients, which contributes to the safety in clinical blood transfusion.

PD-1 and CTLA-4 antibodies offer great hope for cancer immunotherapy. However, many patients are incapable of responding to PD-1 and CTLA-4 blockade and show low response rates due to insufficient immune activation. The combination of checkpoint blockers has been proposed to increase the response rates. Besides, antibody drugs have disadvantages such as inclined to cause immune-related adverse events and infiltration problems. In this study, we developed a cyclic peptide C25 by using Ph.D.-C7C phage display technology targeting LAG-3. As a result, C25 showed a relative high affinity with human LAG-3 protein and could effectively interfere the binding between LAG-3 and HLA-DR (MHC-II). Additionally, C25 could significantly stimulate CD8 T cell activation in human PBMCs. The results also demonstrated that C25 could inhibit tumor growth of CT26, B16 and B16-OVA bearing mice, and the infiltration of CD8 T cells was significantly increased while FOXP3 Tregs significantly decreased in the tumor site. Furthermore, the secretion of IFN- by CD8 T cells in spleen, draining lymph nodes and especially in the tumors was promoted. Simultaneously, we exploited T cells depletion models to study the anti-tumor mechanisms for C25 peptide, and the results combined with MTT assay confirmed that C25 exerted anti-tumor effects CD8 T cells but not direct killing. In conclusion, cyclic peptide C25 provides a rationale for targeting the immune checkpoint, by blockade of LAG-3/HLA-DR interaction in order to enhance anti-tumor immunity, and C25 may provide an alternative for cancer immunotherapy besides antibody drugs.

Objective To study the change patterns of bone microstructural parameters around the magnesium based- implants after implantation in rabbit femur at different implantation time points. Methods The threaded and non-threaded high-purity magnesium (HP Mg, 99.99 wt.%) screws, with a 2 mm diameter and a 7 mm length, were implanted into the femoral condyle of the rabbits. The control group was the drilled and healthy group. Micro-CT scanning and analysis were performed at 8th, 12th and 16th week after operation. The obtained microstructural parameters included bone mineral density (BMD), bone volume fraction (BV/TV), trabecular thickness (Tb.Th), trabecular number (Tb.N), trabecular separation (Tb.Sp). Results At 8th week, BMD and BV/TV in non-threaded magnesium screw group were significantly higher than those in healthy group, Tb.N was significantly higher than that in drilled and healthy group, and Tb.Sp was significantly lower than that in healthy group. At 12th week, BMD, BV/TV and Tb.N in threaded magnesium screw group were significantly higher than those in drilled and healthy group, Tb.Th was significantly higher than that in healthy group, and Tb.Sp was significantly lower than that in drilled and healthy group. At 16th week, BMD, BV/TV and Tb.N in non-threaded magnesium screw group were significantly higher than those in drilled and healthy group, and Tb.Sp was significantly lower than that in drilled and healthy group. Conclusions The magnesium based-implant promoted higher BMD, BV/TV, Tb.Th, Tb.N and lower Tb.Sp of surrounding implant, indicating that osseointegration and bone growth were in good condition. Magnesium based-implant could effectively promote the regeneration of bone. The results provide a theoretical basis for the orthopedic application of magnesium based-implants in clinic.

Objective To compare the in vivo degradation rates of two different kinds of high purity magnesium bone screws by animal experiments, so as to make some suggestions on structural design of high purity magnesium bone screws. Methods High purity magnesium bone screws with threads and without threads were implanted into femoral condyles of New Zealand rabbits separately. Twenty-four rabbits were randomly divided into 3 groups. They were euthanized at 8, 12 and 16 weeks after operation, respectively. The in vivo degradation rates of bone screws with two different shapes were compared through micro-CT scanning and Skyscan CT-analyser software, and the stress changes during the progress of bone screw degradation were analyzed. Results The initial surface area of threaded screws ［(31.70±0.06) mm2］ was significantly greater than that of the non-threaded ones ［(29.56±0.22) mm2］. After 8, 12 and 16 weeks, the volume loss ratios of the threaded screws were (26.01±3.44)%, (33.35±5.05)%, (36.84±6.99)%, respectively, and the volume loss ratios of the non-threaded screws were (22.53±4.78)%, (31.12±6.59)%, (43.22±9.31)%, respectively. At the same time point, there were no significant differences in the volume loss ratio between two kinds of screws. The relationship between the volume reduction and the implantation time was linear for non-threaded screws and gradually decreasing for threaded screws. Conclusions Under the low-bearing condition, different structural design for high purity magnesium screws has no obvious effect on their degradation rate in vivo.

Objective Because of statistical noise in Monte Carlo dose calculations,the effective point doses may not be accurately calculated.A user-defined sphere volume was adopted to substitute the effective point to take sphere sampling around the effective point,which minimize the random errors and improve the accuracy of statistical dose.Methods Direct dose measurements were performed at 0°and 90° using a 0.125 cm3 Semiflex ionization chamber (IC) 31010 isocentrically placed in the center of a homogeneous Cylindric sliced RW3 phantom (PTW,Germany).In the scanned CT phantom series,the sensitive volume length of the IC (6.5 mm) was delineated and the isocenter was defined as the simulated effective point.All beams were simulated in the treatment planning system (TPS) in accordance to the measured model.The grid spacing was calculated by 2 mm voxels and the relative standard deviation should be ≤ 0.5％.The statistical and measured doses were statistically compared among three IC models with different electron densities (ED;esophageal lumen ED =0.210 g/cm3 for model A,air ED =0.001 g/cm3 for model B and the default CT scanned ED for model C) at different sampling sphere radius (2.5,2.0,1.5 and 1.0 mm) to evaluate the effect of Monte Carlo.calculation uncertainty upon the dose accuracy.Results In the Monaco TPS,the statistical value was in the highest accordance with the measured value with an absolute average deviation of 0.49％ when the IC was set as esophageal lumen ED =0.210 g/cm3 and the sampling sphere radius was 1.5 mm.When the IC was set as air ED=0.001 g/cm3 and default CT scanned ED,and,the recommended statistical sampling sphere radius was 2.5 mm,the absolute average deviations were 0.61％ and 0.70％.Conclusion In the Monaco TPS,the calculation model with an ED of 0.210 g/cm3 and a sampling radius of 1.5 mm is recommended for the ionization chamber 31010 to substitute the effective point dose measurement to decrease the random stochastic errors of Monte Carlo.

Objective To study the effects of mechanical load on in vivo degradation performance of high-purity magnesium (HP Mg, 99.99 wt.%) quantitatively. Methods Cylindrical Mg specimens, with a 2 mm diameter and a 14 mm length, were mounted in polyetheretherketone (PEEK) rings to bear compressive stresses ［（6.2±0.6） MPa］, tensile stresses ［（4.6±0.1） MPa］ or no stress (as control). The specimens under different stress states were implanted subcutaneously in dorsal abdominal regions of SD rats for 4 weeks. The mass loss, residual volume and surface morphology of the specimens and staining of surrounding soft tissues were used to analyze the degradation rate of HP Mg. Results Specimens and rings were completely encapsulated by membranous tissues after implantation for 4 weeks. No significant differences in the degradation rates were noted between specimens bearing stress and the control. The corrosion layers of specimens under each stress state were uniform. Conclusions The compressive and tensile stresses (4-6 MPa) could not affect significantly HP Mg degradation performance in vivo. The research findings provide theoretical references for the design and clinical application of Mg-based degradable implants.

BACKGROUND: Inert biomaterials such as metal usually hold poor biocompatibility and weak bonding force, which is against the effect of dental or bone implants. Therefore, how to improve their biocompatibility has become the research hotspot.OBJECTIVE: To prepare collagen-coated titanium alloy (Ti6Al4V), and to assess its biocompatibility.METHODS: Ti6Al4V served as the matrix, the 3-amino propyl triethoxy silane (KH550) as the crosslinking agent, and the three-dimensional printed titanium alloy coated by collagen type Ⅰ and Ⅱ was prepared,respectively. The coated materials were co-cultured with mouse preosteoblasts MC-3T3-E1 to evaluate its biocompatibility. The effect of different kinds of collagen on the cell differentiation was compared by differential recognition of surface proteins.RESULTS AND CONCLUSION: When the N content on the titanium alloy surface (Φ10 cm) was 8.41%, the cladding quantity of collagen type Ⅰ and Ⅱ was 0.81 and 0.77 mg, respectively. Compared with the bare titanium alloy, the cell adhered well and distributed extensively on the coated titanium alloy,which showed strong viability and fast proliferation.The cells cultured on collagen type Ⅰ coated materials expressed the proteins associated with matrix synthesis, and those on collagen type Ⅱ coated materials expressed the proteins associated with mineralization. These results clarify that the collagen coating can improve the biocompatibility of titanium alloy, and different types of collagens act on different functional proteins.

Objective:To analyse the effects of mandibular swing approach in the treatment of the tumors in infratemporal fossa. Methods:11 patients with tumors in infratemporal fossa treated by the surgical operation with mandibular swing approach. The mandi-ble cut was at the front of foramina mentale in 5 cases, at the front of mandible angle in 4 cases and at the middle of chin in 2 cases re-spectively. Results:According to the nature, location, size and the relationship of the tumors with peripheral nerve and blood vessels, flexible selection of the position of mandibular cut could fully expose and completely remove the infratemporal fossa tumor. Conclusion:Surgical treatment of the tumors in infratemporal fossa by mandibular swing approach is safe and effective.