Objective To evaluate the feasibility of apply Ion Proton semiconductor sequencing platform in non-invasive prenatal genetic diagnosis .Methods Totally 1 000 pregnant women with a singleton pregnancy of 12-32 weeks gestation were selected from the Third affiliated Hospital of Zhengzhou University from Jan to Dec 2013.Using noninvasive prenatal genetic diagnosis based on Ion Proton semiconductor sequencing platform to study their cffDNA .In parallel, 72 pregnant women received invasive prenatal diagnosis by traditional chromosomal analysis with amniocentesis chorionic villus sampling .Results It′s shown that 18 out of 1 000 (1.8%) pregnant women underwent the noninvasive prenatal genetic testing had a high risk for aneuploid chromosomes , including 7 cases of 21-trisomy, 4 cases of 18-trisomy, 2 cases of 13-trisomy, 4 cases of sex chromosomal abnormality , and 1 case of 15-trisomy.It demonstrated that the rate and accuracy of fetal 21-trisomy, 13-trisomy and 18-trisomy by non-invasive prenatal genetic testing were both 100%without misdiagnosis , the rate of detection for sex chromosomal abnormality was 2/2 with a false positive rate of 1/3.However, the 15-trisomy predicted by the non-invasive prenatal diagnosis in a woman was finally proved to be a false positive .Based on the results by karyotyping (55/55) as well as follow-ups (493/493), the specificity of the non-invasive prenatal diagnosis for detection of 21-trisomy, 18-trisomy and 13-trisomy was 100%.One Ion PITM chip could detect 12 to 15 samples in 1.5 h and the whole process of noninvasive detection could be completed in 1 to 1.5 days.Conclusions The non-invasive prenatal diagnosis by Ion Proton semiconductor sequencing platform could provide fast and accurate detection of fetal aneuploidy .The benchtop high-throughput sequencing platform has laid the foundation for the independent application in clinical settings for fetal aneuploidy detection .

Objective:To prepare dual-targeted lipid ultrasound microbubbles loaded with ANM33 (HA-PANBs) and evaluate its feasibility in targeting foam cells by stages and achieving precise intracellular drug release in vitro. Methods:The dual-targeteded lipid ultrasound microbubbles were designed with nanobubbles (NBs) as the microbubble core, hyaluronic acid (HA) as the first-stage targeting ligand for damaged endothelial cells, aptamer PM1 as the second-stage targeting moiety for foam cells, and ANM33 as the therapeutic factor. Simultaneously with the characterization of the lipid bubbles, the stability and in vitro contrast-enhanced ultrasound imaging capability were detected. Then a co-culture model of damaged human umbilical vein endothelial cells (HUVEC) and macrophages (RAW264.7, MΦ) was established, combined with flow cytometry, oil red O staining and small animal in vivo imaging to evaluate the ability of HA-PANBs in targeting foam cells precisely and releasing ANM33. Results:The HA-PANBs exhibited regular morphology and good structural stability, with a particle size of (1 357.53±140.20)nm and a surface potential of (-5.61±0.73)mV. HA, PM1 and ANM33 were effectively connected. In the damaged HUVEC/MΦ co-culture system, the HA-PANBs group demonstrated the best targeting effect on foam cells, with an effective uptake of (80.65±2.12)%, which was 56.74% higher than that of the NBs group. Oil red O staining revealed that the cholesterol efflux capacity of foam cells in the HA-PANBs group was significantly better than that in the NBs group, the results were statistically different [(629.80±21.99) a.u.vs (1 071.00±55.49)a.u., P<0.05]. Conclusions:The dual-targeted lipid ultrasound microbubbles (HA-PANBs) can precisely target foam cells and significantly enhance their cholesterol efflux, providing a new strategy for the early non-invasive diagnosis and treatment of atherosclerosis.

Objective:To investigate the expression levels of serum KLK5, IL-17 and IL-18 in patients with rosacea and their clinical significance.Methods:A prospective study included 65 patients with rosacea from the Department of Dermatology, Sichuan Provincial People＇s Hospital, from May to October 2022. There were 8 males and 57 females with an average age of (30.9±9.8) years, including 47 cases of erythematotelangiectatic type and 18 cases of papulopustular type. Twenty healthy individuals from the same hospital＇s physical examination during the same period were included as control group, consisting of 3 males and 17 females with an average age of (33.8±10.0) years. Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of serum KLK5, IL-17, and IL-18. Investigator＇s global assessment (IGA) score was used to assess the severity of papules and pustules, and clinical erythema assessment (CEA) score was used to assess the severity of persistent erythema. The expression levels of serum KLK5, IL-17, and IL-18 were compared between the two groups, and the correlation between the severity of the disease and the expression levels of KLK5, IL-17, and IL-18 was analyzed. Additionally, the expression levels of KLK5, IL-17, and IL-18 in different subtypes of rosacea were compared.Results:The expression levels of serum KLK5, IL-17, and IL-18 in the rosacea group were (3134.01±448.82), (154.78±37.64), (236.24±38.81) pg/ml, respectively, all of which were higher than those in the healthy control group (2421.54±340.07), (95.36±24.94), (181.61±23.88) pg/ml, with statistically significant differences (all P<0.05). The levels of serum KLK5, IL-17, and IL-18 in patients with rosacea were positively correlated with IGA scores ( r=0.534, 0.767, 0.417) and CEA scores ( r=0.852, 0.459, 0.309) (all P<0.05). There were no statistically significant differences in the expression levels of serum KLK5, IL-17, and IL-18 between the erythematotelangiectatic and papulopustular subtypes of rosacea (all P>0.05). Conclusions:The expression levels of serum KLK5, IL-17 and IL-18 in patients with rosacea are higher than those in the healthy control group and are positively correlated with the severity of rosacea.