Immune evasion has made ovarian cancer notorious for its refractory features, making the development of immunotherapy highly appealing to ovarian cancer treatment. The immune-stimulating cytokine IL-12 exhibits excellent antitumor activities. However, IL-12 can induce IFN-γ release and subsequently upregulate PDL-1 expression on tumor cells. Therefore, the tumor-targeting folate-modified delivery system F-DPC is constructed for concurrent delivery of IL-12 encoding gene and small molecular PDL-1 inhibitor (iPDL-1) to reduce immune escape and boost anti-tumor immunity. The physicochemical characteristics, gene transfection efficiency of the F-DPC nanoparticles in ovarian cancer cells are analyzed. The immune-modulation effects of combination therapy on different immune cells are also studied. Results show that compared with non-folate-modified vector, folate-modified F-DPC can improve the targeting of ovarian cancer and enhance the transfection efficiency of pIL-12. The underlying anti-tumor mechanisms include the regulation of T cells proliferation and activation, NK activation, macrophage polarization and DC maturation. The F-DPC/pIL-12/iPDL-1 complexes have shown outstanding antitumor effects and low toxicity in peritoneal model of ovarian cancer in mice. Taken together, our work provides new insights into ovarian cancer immunotherapy. Novel F-DPC/pIL-12/iPDL-1 complexes are revealed to exert prominent anti-tumor effect by modulating tumor immune microenvironment and preventing immune escape and might be a promising treatment option for ovarian cancer treatment.

Objective:To design a novel electromagnetic ejection device for endoscopic suturing to achieve continuous deployment of suture nails.Methods:An electromagnetic ejection device and its accompanying suture nail structure were designed and a prototype was fabricated based on electromagnetic ejection principles. A finite element model of the electromagnetic ejection device was constructed to study the effects of armature-coil center distance and different driving voltages on suture nail ejection speed. An experimental platform for testing electromagnetic ejection velocity was constructed, and a high-speed camera was used to detect the ejection velocity. A platform for the suture embedding experiment was built to measure the effects of different voltages on the inserting speed of suture into the gastric wall tissue. A platform for a suture extraction force experiment was built to evaluate the extraction force of sutures embedded in tissues under different driving voltages.Results:A suture nail structure and electromagnetic ejection device were designed, and a prototype was fabricated. The ejection velocity increased and then decreased with the increase of the armature-coil center distance, and the maximum ejection velocity was 15.81 m/s at the center distance of 18 mm. At this distance, the voltage was linearly related to the ejection velocity, and the experimental values of the staple basically coincided with the simulated values. When the driving voltage was in the range of 150 to 180 V, the suture nails could successfully insert in the tissues, and the 180 V voltage group had a greater insertion depth. The extraction force of the suture nails at 120, 150, 180, and 210 V voltages were (0.49 ± 0.19), (1.14 ± 0.19), (1.23 ± 0.15), and (1.85 ± 0.31) N, respectively.Conclusions:A novel electromagnetic ejection device for endoscopic suturing is proposed that is capable of continuous firing of suture nails. This device provides a new long-distance driving method for intelligent, minimally invasive surgical instruments.

BACKGROUND:With the increasing number of tendon transplantation surgeries for tendon injuries,the demand for tendon tissue engineering scaffolds is increasing.Research has found that good pore size and porosity of implants contribute to tissue healing. OBJECTIVE:To review the types of materials currently published for tendon tissue engineering scaffolds and investigate the correlation between various tendon tissue engineering scaffold materials and pores. METHODS:Articles were retrieved on PubMed,Embase,and Web of Science databases,using keywords"tendon"or"ligament"and"tissue scaffold"as well as"porosity"or"permeability".A total of 84 articles meeting the criteria were included to summarize,discuss and anticipate future development directions. RESULTS AND CONCLUSION:The materials used in the research of tendon tissue engineering are mainly divided into two categories:natural tendon scaffold materials and artificial synthetic tendon scaffold materials.Natural scaffold materials include autologous tendons,allogeneic tendons,and xenogeneic tendons.Autogenous tendons and allogeneic tendons have been used in clinical practice for many years.During the preparation of allogeneic tendons and animal experiments,it was found that the process of acellular disinfection resulted in an increase in the pore size and porosity of both types of tendons,but the specific reasons and mechanisms have not been further studied.There are many types of artificial tendon scaffold materials currently being studied,among which artificial ligament products such as Leeds Keio and LARS(Ligament Advanced Reinforcement System)are still in use in some countries.Other materials have not been promoted in clinical practice due to immature technology and other issues.The pores and porosity of artificial tendon scaffold materials also show different trends due to their different materials and preparation techniques.

Objective: To examine the association between noise exposure in daily life and depressive symptoms, so as to provide the evidence for reducing the impact of noise in daily life on depressive symptoms. Methods: Based on the 2015 to 2020 database of National Health and Nutrition Examination Survey, demographic information and noise exposure in daily life were collected from people aged 18 years and over. Depressive symptoms were evaluated using the Patient Health Questionnaire-9. The relationship between noise exposure in daily life and depressive symptoms were analyzed using a multivariable logistic regression model. Results: A total of 3 216 individuals were enrolled, including 1 707 males (53.08%) and 1 509 females (46.92%). The mean age was (49.30±18.07) years. There were 491 individuals with noise exposure in daily life, accounting for 15.27%. There were 265 cases with depressive symptoms, accounting for 8.24%. There were 66 individuals exposed to noise in daily life in the group with depression symptoms (24.91%), and 425 individuals exposed to noise in daily life in the normal group (14.40%), with statistically significant difference in noise exposure in daily life between the two groups (P<0.05). Multivariable logistic regression analysis showed that after adjusting for gender, age, educational level, marital status, household income poverty ratio, sleep duration, alcohol consumption and hearing, individuals who had noise exposure in daily life (OR=1.743, 95%CI: 1.258-2.413) were more likely to have high risk of depressive symptoms. Conclusion Noise exposure in daily life was associated with an increased risk of depressive symptoms.

Objective To improve the efficiency and quality of end-to-end anastomosis,a novel degradable vascular anastomotic device was designed,and the relationship between pressure distances and biomechanical properties of the anastomotic stoma was explored.Methods The three-dimensional(3D)structure of the vascular anastomotic device was designed and the prototype was fabricated with extruded high-purity magnesium.The finite element model of the end-to-end vascular anastomosis was established to study the stress distributions of the anastomotic end face under different pressure distances(0.4,0.5,0.6,0.7,and 0.8 mm)and their change rules.In vitro experiments were conducted to verify the rationality of the finite element results as well as the feasibility and effectiveness of the vascular anastomotic device.Results When the pressure distance was 0.6 mm,the anastomotic tensile force,and burst pressure could reach(11.79±0.64)N and(39.32±2.99)kPa,respectively,meeting the clinical requirement for the strength of vascular anastomosis,and with the minimal mechanical damages to tissues.Conclusions The device designed in this study can be used for vascular anastomosis by adjusting the pressure distance,and it can improve operation efficiency,reduce mechanical damage to tissues,and further improve the quality of anastomosis.These results provide an essential reference for the design of degradable vascular anastomotic devices.

Objective Aiming at improving biomechanical strength of the anastomotic stoma as well as reducing tissue thermal damage, a novel radiofrequency (RF) tissue welding electrode was developed. Methods A novel electrode with a hollow structure on the surface ( the plum electrode) was designed and the ring electrode was used as control group to conduct the welding of intestinal tissues based on RF energy. Biomechanical properties of anastomotic stoma were studied by shear test and burst pressure test. The tissue thermal damage during welding was investigated by finite element electro-thermal-mechanical multi-field coupling simulation analysis and thermocouple probe, and the tissue microstructures were also studied. Results Under 120 W RF energy, 8 s welding duration and 20 kPa compression pressure, the anastomotic stoma had the optimal biomechanical properties. Compared with the ring electrode group, biomechanical strength of the anastomotic stoma in plum electrode group was higher, with the shear strength and burst pressure increasing from (9. 7±1. 47) N, (84. 0±5. 99) mmHg to (11. 1±1. 71) N, (89. 4±6. 60) mmHg, respectively. There was a significant reduction in tissue thermal damage, and intact and fully fused stomas could be formed in anastomotic area. Conclusions The proposed novel electrode could improve biomechanical strength of the anastomosis as well as reduce tissue hermal damage, thus achieve better fusion. The research result provide references for realizing the seamless connection of human lumen tissues

Objective: To investigate the value of combined stool syndecan-2 (SDC2) and tissue factor pathway inhibitor 2 ( TFPI2) gene methylation testing in the early screening of colorectal cancer． Methods : 106 patients with colorectal cancer (colorectal cancer group) ，75 patients with advanced adenoma ( advanced adenoma group) and 35 patients with non-advanced adenoma (non-advanced adenoma group) were selected as study subjects，and 153 patients with other gastrointestinal disorders and 182 patients with negative colonoscopy results during the same period were selected as the control group．The quantitative methylation-specific PCR(qMSP) method was used to detect SDC2 and TFPI2 gene methylation in the stool specimens of all subjects．The sensitivity and specificity of the combined SDC2 and TFPI2 gene methylation assay for the detection of colorectal cancer and adenoma were evaluated using colonoscopy and pathology results as the gold standard. Results : Among 106 patients with colorectal cancer， the sensitivity of combined methylation test was 93. 4% ; among 75 patients with advanced adenoma，the sensitivity of combined methylation test was 62. 7% ; among 35 patients with non-advanced adenoma，the sensitivity of combined methylation test was 34. 3% ; the specificity of the combined SDC2 and TFPI2 gene methylation test for colorectal cancer and adenoma screening was 94. 6%． Conclusion The combined SDC2 and TFPI2 gene methylation test has high sensitivity for colorectal cancer and its early lesions，and it also maintains high specificity.

Objective The ileum of porcine intestines with radiofrequency (RF) energy was fused through a novel linkage-type pressure controlled electrode, so as to verify feasibility and security of intestinal reconstruction in the RF energy tissue fusion technology. Methods Fresh porcine intestines were fixed on negative electrode in the order of ‘mucosa-serosa’, and then different compressive pressures （497，796，995，1 194，1 492 kPa）and RF energy were applied to the tissues through positive electrode of pressure cone to complete intestinal anastomosis. Biomechanical properties of the fused area were studied by tensile strength and bursting pressure test, and the thermal diffusion and tissue microstructure also studied. ResultsThe anastomotic tensile strength and bursting pressure could reach （8.73±1.11） N and （8.29±0.41） kPa, respectively, when the energy output power, pressure and welding time were 160 W, 995 kPa and 13 s, respectively, and an intact microstructure with little free collagen in the fused area could be observed. Conclusions The technology of RF energy-based tissue fusion could accomplish fast and stable intestinal tract reconstruction, showing great potential in clinical application. It is of great significance to shorten the operation time, simplify the operation process and improve the operation quality.

Objective To develop a new type of electric stapler, so as to solve the problems of insufficient rotation angle, inconvenient operation and difficulty in controlling the pressing strength of existing products. Methods An electric stapler was designed and manufactured. The motion trajectory curve of the prototype was measured by using the three-coordinate imaging instrument to build functional test platform of the prototype, and the goodness of fit was used to evaluate consistency between the theoretical curve and the measured curve. The small intestine tissues of fresh pig were anastomosed at different bending angles of the front end, and the forming rate of the anastomotic stoma was measured. Results The goodness of fit between the test curve and the theoretical curve for both turning motion and shooting motion was ideal, while the goodness of fit between the test curve and the theoretical curve for pressing motion was not ideal when the turning joint was bent at 0°-30°, and was ideal when it was bent at 45°-60°. In performance test, the deformity rate of the nail was smaller than 1.14%, indicating that the bending angle had no significant impacts on the anastomotic effect. Conclusions The kinematics curves of shooting motion and turning motion are consistent with the theoretical curves. The pressing motion curves fluctuate at different bending angles, which will not affect the anastomotic effect, and the effect of the electric stapler meets the clinical requirements.

Objective: To evaluate the effect of Annexin-A1 mimetic peptide Ac2-26 on activation of astrocytes in rats. Methods: The primarily cultured astrocytes from the cortex of fetal Sprague-Dawley rats after 4 passages were divined into 4 groups (n=24 each) using a random number table method: control group (C group), LPS group, LPS+ scramble peptide group (LPS+ Src group) and LPS+ Ac2-26 group.LPS was added to LPS group with the final concentration of 1 mg/ml.LPS at the final concentration of 1 mg/ml and scramble peptide at the final concentration of 3.3 mmol/L were added to LPS+ Src group.LPS at the final concentration of 1 mg/ml and Ac2-26 at the final concentration of 3.3 mmol/L were added to LPS+ Ac2-26 group.After 24-h incubation, the cell survival rate was measured by CCK-8 assay, the migration was determined by Transwell assay, the concentrations of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1a (MIP-1a) in the supernatant were measured (by enzyme-linked immunosorbent assay), and the expression of glial fibrillary acidic protein (GFAP), extracellular signal-regulated kinase (ERK), phosphorylated ERK (p-ERK), c-Jun N-terminal kinase (JNK), phosphorylated JNK (p-JNK), p38 mitogen-activated protein kinase (p38MAPK), and phosphorylated p38MAPK (p-p38MAPK) in astrocytes was detected by Western blot. Results: Compared with group C, the expression of GFAP was significantly up-regulated, and the cell mobility, concentrations of TNF-α, IL-1β, MCP-1 and MIP-1α in the supernatant, p-ERK/ERK ratio, p-JNK/JNK ratio and p-p38MAPK/p38MAPK ratio were increased (P<0.05), and no significant change was found in the cell survival rate in group LPS (P>0.05). Compared with group LPS, the expression of GFAP was significantly down-regulated, and the cell mobility, concentrations of TNF-α, IL-1β, MCP-1 and MIP-1α in the supernatant, p-JNK/JNK ratio and p-p38MAPK/p38MAPK ratio were decreased in group LPS+ Ac2-26 (P<0.05), and no significant change was found in the parameters mentioned above in group LPS+ Src (P>0.05). Conclusion Ac2-26 can inhibit activation of astrocytes and produces anti-inflammatory effect in rats.