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 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.

Background/Aims: This study aimed to explore the effect of gut microbiota-regulated Kupffer cells (KCs) on colorectal cancer (CRC) liver metastasis. Methods: A series of in vivo and in vitro researches were showed to demonstrate the gut microbiota and its possible mechanism in CRC liver metastasis. Results: Fewer liver metastases were identified in the ampicillin-streptomycin-colistin and colistin groups. Increased proportions of Parabacteroides goldsteinii, Bacteroides vulgatus, Bacteroides thetaiotaomicron, and Bacteroides uniforms were observed in the colistin group. The significant expansion of KCs was identified in the ampicillin-streptomycin-colistin and colistin groups. B.vulgatus levels were positively correlated with KC levels. More liver metastases were observed in the vancomycin group. An increased abundance of Parabacteroides distasonis and Proteus mirabilis and an obvious reduction of KCs were noted in the vancomycin group. P. mirabilis levels were negatively related to KC levels. The number of liver metastatic nodules was increased in the P. mirabilis group and decreased in the B. vulgatus group. The number of KCs decreased in the P. mirabilis group and increased in the B. vulgatus group. In vitro, as P. mirabilis or B. vulgatus doses increased, there was an opposite effect on KC proliferation in dose- and time-dependent manners. P. mirabilis induced CT26 cell migration by controlling KC proliferation, whereas B. vulgatus prevented this migration. Conclusions An increased abundance of P. mirabilis and decreased amount of B. vulgatus play key roles in CRC liver metastasis, which might be related to KC reductions in the liver.

Objective:To assess the predictive values of bioelectrical impedance analysis(BIA)-measured body fat indices to abnormal lipid profiles, and to preliminary propose optimal cut-off values of body fat in children and adolescents.Methods:Children and adolescents, aged 6-16 years, were selected from 30 schools (8 primary schools, 21 middle schools and one 12-year education school) in Dongcheng, Tongzhou, Fangshan and Miyun districts of Beijing by adopting a stratified cluster sampling method from November 2017 to January 2018.Questionnaire survey, body mass index(BMI), body fat mass index (FMI), fat mass percentage (FMP) and four lipid profiles were conducted.Results:A total of 14 309 participants, aged (11.0±3.3) years, were enrolled in the analysis, with 49.9% boys.In boys and girls, the percentile values ( P60- P95) fitted by FMI and FMP with K-median-coefficient of variation(LMS) method were taken as the cutting points, and P75 values were selected as the cut-off points of excessive body fat for their better sensitivity, specificity, predictive value and area under curve (AUC) for identification of abnormal lipid profiles.Boys with FMI above P75 accounted for 28% of the total population, and controlling boys with FMI below P75 could prevent dyslipidemia of 8%-57%.FMI in girl population occupied about 26% of the above, and controlling FMI in girl population below this cut-off point may prevent dyslipidemia from 8%-42%.FMP observed similar results to FMI.Assessed by FMI or FMP with P75 cut-off values, adiposity performed better than BMI for recognizing abnormal lipid profiles in boys (AUC: 52.4%-69.6% vs.50.2%-67.1%, P<0.05) rather than in girls ( P>0.05). In addition, when FMI or FMP beyond P90, the specificity of each abnormal lipid profiles was around 90%. Conclusions:The recommend cut-off points for body fat may be to assess children′s adiposity, and can be applied in preventive activities.

Although immune checkpoint inhibitors (ICIs) have great breakthrough in cancer treatment in recent years, most patients have not benefited from it on account of immune microenvironment. Studies have shown that tryptophan metabolism is not only involved in the formation of tumor immunosuppressive microenvironment but also plays an important role in the therapeutic application of ICIs. At present, inhibiting the kynurenine pathway of tryptophan metabolism is now in various stages of clinical trials, while the other two metabolic pathways, 5-HT and the indole pathway, also have aroused wide concern. This article reviews the latest developments in this field.

Objective:To investigate the relationships between hyperuricemia and the incidence risk for cardiometabolic abnormity in children.Methods:Data were obtained from School-based Cardiovascular and Bone Health Promotion Program. In 2017, a total of 15 391 children aged 6-16 years in Beijing were selected through stratified cluster sampling at baseline survey. Follow-up investigation was conducted in 2019. Logistic regression model was used to analyze the relationships of uric acid quartiles and change in uric acid levels with incidence risks for cardiometabolic abnormity (hypertension, hyperglycemia and dyslipidemia).Results:A total of 8 807 children (4 376 boys, 4 431 girls) were included in the analysis, the average age of the children was (11.1±3.3) years at baseline survey. The adjusted odds ratios ( ORs) and 95% confidence intervals ( CIs) of incidence risk for hypertension in the third and fourth quartiles of the UA were 1.39 (1.11-1.75) and 1.56 (1.19-1.81), respectively. The ORs and 95% CIs of risk for high LDL-C in the second, third and fourth quartiles were 1.88 (1.16-3.05),1.98 (1.23-3.17) and 2.25 (1.42-3.57). The uric acid level increased by one standard deviation, the risk increased by 17% for hypertension and 27% for high LDL-C. The uric acid level increased by 10 μmol/L, the risk increased by 2.1% for hypertension and 2.9% for high LDL-C. The gender-stratified analysis showed that the similar results. The ORs and 95% CIs were 1.32 (1.09-1.60) and 1.50 (1.05-2.16) for hypertension, 1.90 (1.38-2.60) and 2.96 (1.58-5.52) for high TC, 1.78 (1.26-2.51) and 2.84 (1.60-5.03) for high LDL-C in the groups of newly diagnosed hyperuricemia and persistent hyperuricemia. Conclusions:Higher uric acid level was associated with increased incidence risks for hypertension, abnormal TC and LDL-C. Maintaining optimal uric acid level by children might contribute to the early prevention of cardiovascular diseases.

Objective:To analyze the influence of obesity status on the development of cardiometabolic disorders in school-age children.Methods:Information about children's body weight, body height and cardiovascular risk factors were collected in baseline survey in 2017 and follow-up survey in 2019. The school-age children were divided into four groups based on their baseline and follow-up obesity status, i.e. sustained non-obesity group, restored obesity group, newly classified obesity group, and persistent obesity group. Analysis of covariance was used to compare the difference of change in levels of cardiometabolic factors among the four groups. The multivariate logistic regression model was used to analyze the relationship between obesity status and the incidence risk of cardiometabolic disorders.Results:The present study included 11 379 school-age children (boys accounting for 49.6%). During the 2 years, the incidence of obesity was 3.2% (95% CI: 2.9%-3.5%) with the restoration ratio of obesity of 4.4% (95% CI: 4.0%-4.8%). Compared with the sustained non-obesity group, increases in SBP, DBP, TG, LDL-C and non-HDL-C were much higher in newly classified obesity group and persistent obesity group, but lower in restored obesity groups except for DBP (all P<0.05). In addition, the incidence risk of hypertension, high glucose, dyslipidemia and cardiometabolic disorders (≥2 risks) were much higher in newly classified and persistent obese children than in sustained non-obese children. No difference was found in incidence risks of most cardiovascular disorders between restored obese children and sustained non-obese children, except for hypertension and cardiometabolic risks. Conclusion:Both newly classified obesity and persistent obesity increased the incidence risks for multi cardiovascular disorders, while these risks could be reduced when non-obese status restore.

Objective:To investigate the incidence and risk factors of pediatric fracture in school-age children and adolescents in Beijing.Methods:A total of 12 056 students with complete fracture data of 2017 baseline survey and 2019 follow-up survey of School-based Cardiovascular and Bone Health (SCVBH) Promotion Program in Beijing were selected as study subjects. Logistic regression model was used to analyze associations of fracture incidence with age, BMI, fracture history and lifestyle.Results:The 2-year accumulative incidence rate of pediatric fracture was 3.1% (95% CI: 2.8%-3.4%) in school-age children and adolescents in Beijing, which was much higher in boys (4.1%) than in girls (2.1%) and increased with age in boys but decreased with age in girls. Fractures mainly occurred at upper-limb (69.0%), no gender and age specific significant in fracture sites were observed. Fracture history was the risk factor for fracture incidence in both boys and girls (boys: RR=1.81, 95% CI: 1.18-2.64; girls: RR=3.11, 95% CI: 1.74-5.13). In addition, higher duration and frequency of moderate to vigorous physical activities (≥120 min/day) and frequent consumption of sugar sweetened beverage (≥1 time/week) were also found to increase fracture risk in boys. Conclusion:The incidence of pediatric fracture was associated with gender, age, fracture history and lifestyle habits in school-age children and adolescents in Beijing. Targeted strategies are needed to prevent childhood fracture.

Objective:To investigate the association between vitamin D nutritional status and the body muscle mass in children.Methods:Data were obtained from School-based Cardiovascular and Bone Health Promotion Program. In 2017, a total of 15 391 children aged 6-16 years in Beijing were selected through stratified cluster sampling in baseline survey. A follow-up investigation was conducted in 2019. The questionnaire survey and the detection of serum 25-hydroxyvitamin D [25(OH)D] level were conducted. The bioelectrical impedance analysis (BIA) apparatus was used to measure body muscle mass, and muscle mass index (MMI) was calculated. Multivariable linear models were used to analyze the association of vitamin D nutritional status with the baseline and follow-up MMI measures.Results:A total of 10 890 children aged (11.5±3.3) years(boys accounting for 49.6%) were included in the analysis. The average 25(OH)D level was (35.4±12.0) nmol/L, with an adequacy ratio of 11.1%. After multivariate linear regression adjustment for age, sex, body fat mass, smoking status, alcohol use status, dairy supplement, calcium supplement, physical activity, and pubertal development, no statistically significant association between vitamin D nutritional status and baseline MMI level was observed ( P>0.05). For the follow-up MMI, the Z-score increased by 0.008 ( P=0.058) for per 10 nmol/L increase in 25(OH)D, which were 0.002 ( P=0.815) and 0.037 ( P=0.031) higher in children with insufficient and adequate vitamin D than those with vitamin D deficiency, respectively ( P for trend =0.089). Subgroup analysis showed that in the normal BMI group, for per 10 nmol/L increase in 25 (OH) D, the MMI at baseline survey and MMI Z-score at follow-up of children with adequate vitamin D and increased by 0.019 and 0.014, respectively (both P<0.05). Conclusions:Vitamin D nutritional status was related to muscle mass in children, and children with adequate vitamin D tended to obtain higher MMI. Children and adolescents are encouraged to maintain sufficient vitamin D levels, strengthen nutrition and exercise to promote body health.

Objective:To investigate the relationships between vitamin D nutritional status and the calcaneal bone mineral density (BMD) in children.Methods:Data were obtained from School-based Cardiovascular and Bone Health Promotion Program. In 2017, a total of 15 391 children aged 6-16 years in Beijing selected through stratified cluster sampling were included in the baseline survey. A follow-up investigation was conducted in 2019. The questionnaire survey, detection of serum 25-hydroxyvitamin D [25(OH)D] level and ultrasound measurement of calcaneal BMD were conducted. Multivariable linear and logistic regression models were used to analyze the relationships between baseline vitamin D nutritional status and the follow-up calcaneal BMD.Results:A total of 10 914 children aged (11.5±3.3) years (boys accounting for 49.6%) were included in the analysis. The average 25(OH)D level was (35.4±12.0) nmol/L, and the deficiency rate was 36.1%. After the adjustment for age, gender, body mass index, smoking status, alcohol use status, dairy products intake, vitamin D supplement, calcium supplement, physical activity, pubertal development, and baseline calcaneal BMD Z-score, for per 10 nmol/L increase in 25(OH)D, the follow-up calcaneal BMD Z-score increased by 0.01( P=0.041), and the OR(95% CI) of decreased calcaneal BMD Z-score after 2 years was 0.96 (0.93-1.00)( P=0.030). Compared with vitamin D adequacy, the follow-up calcaneal BMD Z-score of children with vitamin D insufficiency and deficiency decreased by 0.03( P=0.307) and 0.06 ( P=0.046), and the risk of decreased calcaneal BMD Z-score after 2 years increased by 15%( P=0.037) and 21%( P=0.006), respectively ( P for trend<0.05). Conclusions:Vitamin D nutritional status was closely related to calcaneal BMD, and children with adequate vitamin D nutritional status tended to obtain higher BMD. Children and adolescents are encouraged to maintain sufficient vitamin D levels, strengthen nutrition and exercise to promote bone health.