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Objective:To prepare the resiquimod-loaded lipid microbubbles R848-MBs, evaluate their enhanced ultrasound imaging and high intensity focused ultrasound (HIFU) ablation effects, and explore their ability to improve tumor immune microenvironment synergize with HIFU.Methods:R848-MBs were prepared by the thin film hydration-mechanical shock method; The basic characteristics and safety of R848-MBs were detected, the HIFU controlled-release characteristics were verified in vitro and the drug metabolism and biological distribution were investigated in vivo. The ability of enhancing ultrasound imaging was observed in vitro and in vivo. To investigate the enhanced HIFU ablation effect of R848-MBs, six EMT6 tumor-bearing mice were randomly divided into HIFU group and R848-MBs+ HIFU group, three mice in each group, the changes in contrast average sound intensity before and after ablation in mouse tumor areas and the change of ultrasound image gray value in tumor area were evaluated, the tumor were resected to observe the coagulative necresis by TTC staining and HE staining. Forty-five tumor-bearing mice were randomly divided into control group, Free R848 group, HIFU group, Blank-MBs+ HIFU group and R848-MBs+ HIFU group, nine mice in each group. On the third day after treatment, 3 mice in each group were randomly selected and killed, to evaluate the ability of R848-MBs to improve tumor immune microenvironment synergize with HIFU. The expression level of CRT on the surface of tumor cells were detected by immunofluorescence staining, the proportion of mature DC in lymph nodes, spleen, and CD8 + T cells in spleen were detected by flow cytometry. The treatment effectiveness of each group( n=6) were evaluated by measuring tumor volume, observing and drawing survival curves. Results:The R848-MBs lipid microbubbles with good safety were successfully prepared, with a concentration of 2.58×10 9/ml, as spherical bubbles under optical microscope and laser confocal microscopy, in a particle size of (1.72±0.11)μm, at a surface potential of (-10.16±0.73)mV. The cumulative drug release was up to 83.44% after HIFU (90 W, 3 s) in vitro. The concentration of R848 in plasma decreased rapidly, and the drug concentration in tumor tissue of the R848-MBs+ HIFU group was higher than that of the R848 group 24 hours after treatment ( P<0.01). The ultrasound imaging of R848-MBs was significantly enhanced in contrast mode in vitro and in vivo; R848-MBs can significantly enhance the HIFU ablation effect, the contrast average sound intensity change in the tumor area before and after ablation in the R848MBs+ HIFU group was greater than that in the R848 group ( P<0.05), and the immediate ultrasound grayscale value change in the HIFU+ R848-MBs group was 46.34±3.21, which was significantly greater than that in the HIFU group (10.67±1.53), with statistical significance ( P<0.000 1). Coagulation necrosis was observed in tumor HE staining and TTC staining. The results of treatment efficacy in vivo showed that R848-MBs+ HIFU group had the strongest therapeutic effect, and R848-MBs combined with HIFU treatment could significantly prolong the survival period of mice compared with intravenous injection of free R848 ( P<0.01). Immunofluorescence staining and flow cytometry results showed an increase in the expression level of CRT on the surface of tumor tissue in the R848-MBs combined with HIFU group, and the percentage of mature DC in tumor draining lymph nodes (58.53±1.04)% were significantly higher than those in the HIFU group (37.56±2.13)% ( P<0.001), and the percentage of mature DC in the spleen (70.65±1.91)% were significantly higher than those in the HIFU group (36.46±3.89)% ( P<0.001), the percentage of CD8 + T cells in the spleen (27.46±3.04)% was significantly higher than that in the HIFU group (18.69±0.29)% ( P<0.01). Conclusions:The HIFU controlled-release lipid microbubbles R848-MBs can not only enhance the efficiency of HIFU ablation, but also improve the tumor immune microenvironment.
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Objective:To investigate the effect of HLA-Cw*0602 and LCE3B_LCE3C-del allele interaction on the risk of psoriasis vulgaris in a population of Mongolian nationality in Inner Mongolia. Methods:A total of 365 Mongolian patients with psoriasis vulgaris who received treatment in The Affiliated Hospital of Inner Mongolia Medical University from January 2006 to December 2015 (case group) and 284 healthy subjects who concurrently received physical examination in the same hospital (control group) were included in this study. After sex and age matching, and quality control, the correlations between HLA-Cw*0602 and LCE3B_LCE3C-del allele and psoriasis vulgaris in a population of Mongolian nationality were analyzed using SPSS 20.0 software. The interaction between HLA-Cw*0602 and LCE3B_LCE3C-del alleles (adjusting for potential confounders including age and sex) was analyzed using logistic regression. Results:Logistic regression interaction item Int of dominant inheritance mode HLA-Cw*0602 allele and recessive inheritance mode LCE3C_LCE3B-del allele revealed OR = 2.38, P = 0.033, and interaction index S = 1.21, indicating that there was a synergistic effect between the two alleles. Conclusion:The co-existence of HLA-Cw*0602 and LCE3B_LCE3C-del may increase the risk of psoriasis vulgaris in a population of Mongolian nationality in Inner Mongolia.
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Objective To study the influence of mobile management software education to the young and middle-aged type 2 diabetes patients′ knowledge and behavior. Methods 130 cases of diabetes patients was selected in 2015.10 to 2016.04 which came from the endocrine ward of the center hospital of Dalian ,68 males and 62 females.63 cases were divided into experimental group and 67 cases in control group, according to the random number table method. The control group was given the regular out-of- hospital management mode, and the experimental group was managed by the diabetes mobile management software. Six months after the intervention, the effects of two groups on blood glucose, metabolic index, diabetes knowledge, self-management efficacy and self-management behavior were observed. Results There was no significant difference in fasting blood glucose, postprandial 2 h bloodglucose and glycosylated hemoglobin between the two groups before the intervention (P > 0.05).After intervention for three months, the date in control group respectively (8.81 ± 2.02) mmol/L, (12.44 ± 2.53) mmol/L, (8.41±1.40)%. experimental group respectively (7.91±2.29) mmol/L, (10.65±2.87) mmol/L, (7.83± 1.25)%. The difference was statistically significant (t=2.320, 3.691, 2.416, P < 0.05 or 0.01). After intervention for six months, these numbers in control group were (7.96±1.79)mmol/L,(10.61±2.12) mmol/L,(7.85±1.24)%. The experimental group were (7.00±2.00) mmol/L, (8.93±2.16) mmol/L, (7.20±1.25)%. The difference was statistically significant(t=2.805, 4.368, 2.914, P < 0.01).Compared the related knowledge scores (Good, general, poor) before intervention ,the difference was not statistically significant (P>0.05).After 3 months of intervention, the cases in control group was 5, 57 ,1 respectively, the experimental group were 15,46,0 respectively. After 6 months intervention, the control group was 40, 32, 0. The experimental group were 48, 14, 0. After 3 months and 6 months intervention. There was significant difference between the two groups, (Z=2.637, 2.055, P<0.01 or 0.05). scores of diabetes mellitus (high level, medium level, low level)in the two groups was no significant difference (P > 0.05), before the intervention. After 3 months intervention ,cases in control group were 49,131respectively, the experimental group were 54,5,0 , after 6 months intervention ,control group were 59,4,0 ,respectively , the experimental group were 61,0,0. After 3 months and 6 months intervention, there was significant difference between the two groups (Z=2.103, 1.992,P<0.05). Diabetes self- management effectiveness score(good, moderate, poor) was compared in two groups. There was no significant difference between the two groups before and after 3 months intervention (P>0.05). After 6 months of intervention, cases in the control group was 9,54,0,respectively, the experimental group were 43, 18, 0, the difference was statistically significant (Z = 6.315, P < 0.01). Conclusions The education model of diabetes mobile management software can help to improve the standard rate of glucose and other metabolic indexes, at the same time also improve the level of knowledge and behavior of middle-aged and young patients with type 2 diabetes, but it′s long-term effect needs further study.
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Objective To study the influence of mobile management software education to the young and middle-aged type 2 diabetes patients′ knowledge and behavior. Methods 130 cases of diabetes patients was selected in 2015.10 to 2016.04 which came from the endocrine ward of the center hospital of Dalian ,68 males and 62 females.63 cases were divided into experimental group and 67 cases in control group, according to the random number table method. The control group was given the regular out-of- hospital management mode, and the experimental group was managed by the diabetes mobile management software. Six months after the intervention, the effects of two groups on blood glucose, metabolic index, diabetes knowledge, self-management efficacy and self-management behavior were observed. Results There was no significant difference in fasting blood glucose, postprandial 2 h bloodglucose and glycosylated hemoglobin between the two groups before the intervention (P > 0.05).After intervention for three months, the date in control group respectively (8.81 ± 2.02) mmol/L, (12.44 ± 2.53) mmol/L, (8.41±1.40)%. experimental group respectively (7.91±2.29) mmol/L, (10.65±2.87) mmol/L, (7.83± 1.25)%. The difference was statistically significant (t=2.320, 3.691, 2.416, P < 0.05 or 0.01). After intervention for six months, these numbers in control group were (7.96±1.79)mmol/L,(10.61±2.12) mmol/L,(7.85±1.24)%. The experimental group were (7.00±2.00) mmol/L, (8.93±2.16) mmol/L, (7.20±1.25)%. The difference was statistically significant(t=2.805, 4.368, 2.914, P < 0.01).Compared the related knowledge scores (Good, general, poor) before intervention ,the difference was not statistically significant (P>0.05).After 3 months of intervention, the cases in control group was 5, 57 ,1 respectively, the experimental group were 15,46,0 respectively. After 6 months intervention, the control group was 40, 32, 0. The experimental group were 48, 14, 0. After 3 months and 6 months intervention. There was significant difference between the two groups, (Z=2.637, 2.055, P<0.01 or 0.05). scores of diabetes mellitus (high level, medium level, low level)in the two groups was no significant difference (P > 0.05), before the intervention. After 3 months intervention ,cases in control group were 49,131respectively, the experimental group were 54,5,0 , after 6 months intervention ,control group were 59,4,0 ,respectively , the experimental group were 61,0,0. After 3 months and 6 months intervention, there was significant difference between the two groups (Z=2.103, 1.992,P<0.05). Diabetes self- management effectiveness score(good, moderate, poor) was compared in two groups. There was no significant difference between the two groups before and after 3 months intervention (P>0.05). After 6 months of intervention, cases in the control group was 9,54,0,respectively, the experimental group were 43, 18, 0, the difference was statistically significant (Z = 6.315, P < 0.01). Conclusions The education model of diabetes mobile management software can help to improve the standard rate of glucose and other metabolic indexes, at the same time also improve the level of knowledge and behavior of middle-aged and young patients with type 2 diabetes, but it′s long-term effect needs further study.
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Objective To investigate the antitumor activity of the procaspase-3 activator SM-1 in BGC-823 cells in vivo and in vitro and the mechanisms.Methods The inhibitory effects of SM-1 on proliferation of BGC-823 cells were evaluated using MTT method, the cell apoptosis rate was detected by flow cytometry, and the expression of caspase-3 protein and procaspase-3 mRNA was detected by Western blotting and RT-PCR, respectively.SM-1 Antitumor activity was evaluated using the xenograft of BGC-823 cells in nude mice.Results SM-1 effectively inhibited the proliferation in vitro and in-duced apoptosis of BGC-823 cells in a dose-dependent manner.After treatment with SM-1 for 48 h, the protein expression levels of caspase-3 and mRNA expression levels of procaspase-3 were increased.SM-1 significantly inhibited growth of BGC-823 xenograft tumor at the 300 mg/kg dose and the inhibition rate was 56.3%(P<0.05).Conclusion SM-1 can significantly inhibit the tumor growth of BGC-823 cells in vivo and in vitro.The mechanism is possibly related to the activation of procaspase-3 and induced apoptosis of tumor cells.
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An ultrasensitive immunoassay was developed based on As3+ and Hg2+ labeled SiO2 @ Au nanoparticles signal tags and hydride generation-atomic fluorescence spectrometry (HG-AFS) for the detection of carcinoembryonic antigen(CEA) and carbohydrate antigen 19-9 (CA 19-9) respectively. Firstly, amino SiO2@ Au NPs were synthesized for selective absorption of As3+ and Hg2+ ions respectively. Subsequently,the secondary antibody (Ab2) of CEA and CA 19-9 was respectively labeled on As3+ or Hg2+-SiO2 @ Au NPs to prepare the corresponding signal tags for CEA and CA 19-9. Based on the sandwich immunoassay scheme, the tags, two antigen and corresponding first antibodies were bio-conjugated on the bottom of 96-well plate at room temperature to form the immunocomplex. After it was dissolved in alkali solution, As3+ and Hg2+ ions were released in solution and detected by HG-AFS, which concentration was proportional with logarithms of CEA and CA 19-9. The reaction conditions were optimized and the tags were characterized. This assay was based on determination of the concentration of As3+ and Hg2+ for quantization of the corresponding CEA and CA 19-9 antigen. The assay showed a wide linear range from 0. 001 to 100. 0 μg / L for CEA and 0. 01-80 U/ mL for CA 19-9, and a lower detection limit of 0. 5 ng / L and 0. 005 U/ mL respectively. This proposed method was used in real serums samples, the results were consistence with that by ELISA. The immunoassay showed three orders of magnitude of sensitivity lower than that of ELISA, which provides a promising simultaneous immunoassay for the early diagnosis of cancer .