To improve the oral bioavailability of insulin, an insulin-loaded enteric polymer-lipid hybrid nanoparticles(INS-NPs L100)was prepared using methoxy PEG-poly(D, L-lactide)(PEG-PLA), phospholipid s75 and Eudragit L100; in vitro and in vivo behaviors of INS-NPs L100 were evaluated. Insulin-loaded polymer-lipid hybrid nanoparticles(INS-NPs)were prepared by W/O/W double emulsion solvent evaporation method. INS-NPs formulation was optimized by single factor experiment using encapsulation efficiency, particle size, and in vitro release behavior of the corresponding INS-NPs L100 as evaluation indexes. The morphology, in vitro drug release profile and hypoglycemic effect of the INS-NPs L100 using the optimal INS-NPs and Eudragit® L100(used as enteric polymer)were assessed. The results showed that the encapsulation efficiency of the optimal INS-NPs was(62. 18±4. 51)%. The average particle size, PDI and Zeta potential was(225. 2±94. 3)nm, 0. 191±0. 068, and -(14. 84±1. 26)mV, respectively. The cumulative drug release from the INS-NPs L100 was only 8. 01% at 2 h in pH 1. 0 HCl solution, exhibiting a slow drug release behavior; while the drug release from INS-NPs L100 was 67. 31% at 6 h in phosphate buffer of pH 6. 8. Mereorer, after oral administration of INS-NPs L100 with a dose of 38 IU/kg, the blood glucose concentration of healthy rats was reduced to 76% of the initial values at 3. 5 h, exhibiting a sustained hypoglycemic effect. In summary, the INS-NPs L100 prepared in this study could effectively decrease the release rate of insulin in gastric juice, improve the stability of protein in the gastrointestinal tract, and provide a new approach for the oral administration of peptides and protein drugs.

Objective To explore the relation between genetic polymorphisms and the expression in colonic tissues of solute-linked carrier family 26 member A3 (SLC26A3) and susceptibility of Crohn's disease (CD) in Han population of Zhejiang Province.Methods A total of 265 CD patients and 566 gender-and age-matched healthy individuals were enrolled.Alleles and genotypes of SLC26A3 (rs17154444,rs7810937,rs7785539,rs2108225,rs6951457) were examined by SNaPshot.The linkage disequilibrium (LD) and haplotype were also analyzed.Eight patients with colonic CD and eight genderand age-matched patients with benign colonic polyps (control group) were selected.The expression level of SLC26A3 protein in the colonic tissue was detected by immunohistochemistry.T test and rank-sum test were performed for statistical analysis.Unconditional Logistic regression analysis was used to analyze the distributions of SLC26A3 polymorphisms and their effects on the clinicopathological features of CD patients.Results The frequencies of mutant allele of rs2108225,rs7785539 and rs6951457 of the CD group were 53.77％ (285/530),4.72％ (25/530) and 2.83％ (15/530),and the frequencies of mutant genotype were 76.23 ％ (202/265),9.43 ％ (25/265) and 5.66 ％ (15/265),which were lower than those of the control group (60.95％,690/1 132;8.13％,92/1 132;6.10％,69/1 132;83.92％,475/566;15.37％,87/566 and 11.84％,67/566),and the differences were statistically significant (all P＜0.05).The frequencies of mutant allele of rs17154444 and rs7810937 of the CD group were 10.19％ (54/530) and 34.91 ％ (185/530),and the frequencies of mutant genotype were 18.49 ％ (49/265) and 56.23 ％ (149/ 265),compared with those of the control group (8.30％,94/1 132;30.92％,350/1 132;15.55％,88/566 and 51.77％,293/566),the differences were not statistically significant (all P＞0.05).The frequency of mutant allele G of rs2108225 in patients with ileal CD was 47.89 ％ (91/190),and the frequency of mutant genotypeAG+GG was 65.26％(62/95),which were both lower than those of colonic CD (61.62％,122/198 and 85.86％,85/99),and the differences were statistically significant (both P＜0.012 5).rs7810937,rs7785539 and rs2108225 were in a strong linkage disequilibrium.The frequencies of haplotypes AGG and ACA of the CD group were 53.96％ (286/530) and 4.34％ (23/530),which were lower than those of the control group (60.07％,680/1 132 and 7.51％,85/1 132),and the differences were statistically significant (52 =5.534,P=0.019;x2 =5.967,P=0.015).And the frequency of haplotype AGA of the CD group was 8.30％ (44/530),which was higher than that of the control group (1.15％,13/1 132),and the difference was statistically significant (x2 =7.793,P＜0.01).Furthermore,the expression level of SLC26A3 protein in colonic tissues of eight colonic CD patients was 0.19±0.07,which was lower than that of patients with benign colonic polyps (0.26 ±-0.03),and the difference was statistically significant (t=2.55,P=0.023).In addition,the expression levels of SLC26A3 protein in patients carrying genotype GG or AG of rs2108225 were 0.19±0.03 and 0.10±0.01,respectively,which were lower than that of patients carrying genotype AA (0.26± 0.02),and the differences were statistically significant (t=3.19,P=0.033;t=9.06,P=0.003).Conclusions The genetic polymorphismns and their haplotypes of SLC26A3 (rs7785539,rs2108225 and rs6951457) are associated with the susceptibility of CD,and SLC26A3 (rs2108225) polymorphism may affect the expression level of SLC26A3 protein in the colonic tissues.

Objective: To discuss the effect of self-efficacy on patients with coronary heart disease cured in general practice department based on Hospital-Community-Patient Integrated Nursing Mode. Methods: From January to April in 2018, 106 patients (51 males and 55 females) with coronary heart disease hospitalized in general practice of hospital were selected as subjects of study. Random number table method was used to divide the patients into control group and intervention group, 53 cases in each group. The intervention group adopted the hospital-community-patient integrated nursing model, while the control group adopted the traditional health education mode after discharge. Self-efficacy evaluation was conducted before intervention, 3 months after intervention and 6 months after intervention. Results: The total score of self-efficacy in the two groups was higher than that before intervention, but the increase in the intervention group was significantly better than that in the control group, the difference was statistically significant (F=34.681, P < 0.01). The total scores of self-efficacy in intervention group were(30.35±2.58), (33.59±2.68) points respectively 3 months and 6 months after intervention, which were higher than (28.95±2.42), (29.10±2.12) points in control group. The difference was significant (t = 3.702, 13.494, P < 0.01). Conclusion Hospital-community-patient integrated nursing model is superior to traditional health education model after discharge, which can significantly improve the self-efficacy of patients with coronary heart disease discharged from general practice department.

Objective:To explore the association of access blood flow measured by ultrasound dilution and color Doppler ultrasound with patency loss of arteriovenous fistula (AVF).Methods:This was a bidirectional cohort study. The adult patients who underwent maintenance hemodialysis (MHD) with AVF in Peking University First Hospital from January 1, 2018 to July 31, 2020 were enrolled. AVF blood flow was measured by ultrasonic dilution method (Qa), and color Doppler ultrasound in cephalic vein and brachial artery. Patients were divided into low Qa (<500 ml/min), normal Qa (500-1 500 ml/min) and high Qa (>1 500 ml/min) groups according to baseline AVF blood flow measured by ultrasonic dilution method. Qa was monitored every 3 months within the first year. The endpoint events of follow-up were defined as AVF patency loss or death. The deadline of the follow-up was July 31, 2022. Linear regression analysis was used to assess the change trend of Qa. Fine and Gray competitive risk model was used to evaluate the cumulative incidence of AVF patency loss. The Cox proportional hazards regression model was used to evaluate the association between access AVF blood flow and patency loss.Results:A total of 163 patients were enrolled, with age of (57.0±13.7) years old and 110 males (67.5%). The median follow-up time was 45(22, 53) months. Forty-four patients (27.0%) had AVF failure, and 29 patients (17.8%) died. The cumulative incidence rates of AVF patency loss in patients with low Qa, low blood flow of brachial artery and cephalic vein (<500 ml/min), and in those with a downward trend of Qa were higher than those in patients with normal or high blood flow, and in those with a upward trend of Qa (Gray′s test, all P<0.05). After adjusted for age, sex, age of fistula, diabetes and vascular stenosis, multivariable Cox regression analysis results showed that baseline Qa<500 ml/min ( HR=3.508, 95% CI 1.382-8.905, P=0.008), baseline brachial artery flow<500 ml/min ( HR=2.413, 95% CI 1.058-5.503, P=0.036) and a downward trend of Qa ( HR=2.498, 95% CI 1.241-5.027, P=0.010) were independently associated with AVF patency loss. Conclusions:Patients with low baseline value or downward trend of AVF blood flow are at significantly higher risk of patency loss. The brachial artery measurement of AVF blood flow is the preference location for color Doppler ultrasonic.