Macrophage LMO7 deficiency facilitates inflammatory injury via metabolic-epigenetic reprogramming

Inflammatory bowel disease (IBD) is a formidable disease due to its complex pathogenesis. Macrophages, as a major immune cell population in IBD, are crucial for gut homeostasis. However, it is still unveiled how macrophages modulate IBD. Here, we found that LIM domain only 7 (LMO7) was downregulated in pro-inflammatory macrophages, and that LMO7 directly degraded 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) through K48-mediated ubiquitination in macrophages. As an enzyme that regulates glycolysis, PFKFB3 degradation led to the glycolytic process inhibition in macrophages, which in turn inhibited macrophage activation and ultimately attenuated murine colitis. Moreover, we demonstrated that PFKFB3 was required for histone demethylase Jumonji domain-containing protein 3 (JMJD3) expression, thereby inhibiting the protein level of trimethylation of histone H3 on lysine 27 (H3K27me3). Overall, our results indicated the LMO7/PFKFB3/JMJD3 axis is essential for modulating macrophage function and IBD pathogenesis. Targeting LMO7 or macrophage metabolism could potentially be an effective strategy for treating inflammatory diseases.

Teaching reform and practice of bioengineering comprehensive experiment based on virtual simulation technology / 生物工程学报

Bioengineering majors require students to acquire excellent abilities of thinking and analyzing complex problems and have high requirements for students' comprehensive practical skills. Because of the professional characteristics, it is necessary to develop students' abilities to solve complex problems via the teaching of a series of experiments. Therefore, it is particularly important to reform the traditional experiment teaching for students majoring in bioengineering to improve the teaching quality, which have great significance for the cultivation of comprehensive talents. In this study, with the advantages of geographical location and resources to cultivate application-oriented innovative talents, the course group of Comprehensive Experiment of Bioengineering has designed the course based on virtual simulation technology in Binzhou University. Taking the experiment of extraction and bioactivity analysis of Suaeda salsa (growing in the Yellow River Delta) polysaccharide in fermentation as a case, we studied the course design idea, experimental process, teaching method and result analysis, and have improved the teaching performance. This case analysis provides new ideas and content reference for the teaching reform of similar courses.

Predictive value of stimulated thyroglobulin for metastases from differentiated thyroid carcinoma be-fore the first 131Ⅰtreatment / 中华核医学与分子影像杂志

Objective To explore the relationship between the stimulated thyroglobulin ( sTg) and site, number and diameter of metastatic lesions in patients with differentiated thyroid carcinoma (DTC) before the first 131 I treatment, and to evaluate the predictive value of sTg for different metastatic sites. Methods A total of 567 DTC patients (179 males, 388 females; age: (45.3±12.3) years) who received the first 131Ⅰ treatment between January 2012 and June 2017 were included. Thyroglobulin antibody (TgAb), sTg and thyroid stimulating hormone ( TSH) were determined within 1 week before 131 I treatment. Metastases were detected by ultrasonography, CT or 18 F-fluorodeoxyglucose ( FDG ) PET/CT, 131 I whole-body scan, SPECT/CT imaging and pathology. sTg levels of patients with different metastatic sites and different metasta-sis numbers or lesion diameters were compared ( Kruskal-Wallis H test) . Spearman correlation analysis was performed on the number, diameter and sTg level of metastases. The receiver operating characteristic ( ROC) curve was used to explore the predictive value of sTg before the first 131 I treatment for DTC metasta-sis. Results The median values of sTg in the bone, lung, lymph node metastases groups and non-metasta-sis group were 500.00, 104.40, 27.45, 2.39μg/L, respectively, and there were significant differences, ex-cept for bone and lung metastases groups ( H range: -294.605 to 175.162, all P<0.05) . The sTg levels of lung metastasis group and lymph node metastasis group were both decreased by the order of metastasis num- bers (≥3, =2, =1;H range:-57.887 to 48.763, all P<0.05) . As to the diameter of metastases, the sTg levels of >2.0 cm, 1.1-2.0 cm, and≤1.0 cm subgroups in the lung metastasis group and lymph node me-tastasis group were also decreased in order ( H range: -69.935 to 61.043, all P<0.05) . Spearman correla-tion analysis showed that the number ( rs=0.568, 0.606) and diameter ( rs=0.806, 0.664) of the metasta-ses in the lung and lymph node metastases group were positively correlated with sTg (all P<0.05). Areas under ROC curves for sTg to predict bone, lung and lymph node metastasis were 0.935, 0.843 and 0.791 re-spectively. The threshold values were 197. 65, 23. 21 and 10. 96 μg/L respectively. The sensitivities and the specificities were 91.70％, 79.60％, 67.20％ and 97.20％, 80.80％, 82.70％ respectively. Conclusions Tg level before the first 131 I treatment has a certain predictive value for the metastasis, metastatic site and num-ber or diameter in DTC patients.

Effect of liraglutide on glucagon secretion in obese type 2 diabetic patients / 中华内科杂志

Objective To investigate the effect of liraglutide on glucagon release in obese type 2 diabetes (T2DM). Methods A multi-center, prospective, and self-comparison study was conducted in four hospitals in Qingdao. Twenty-four patients with T2DM were selected and treated with liraglutide for 12 weeks. Glucagon levels before and after treatment were detected before and 30 min, 60 min and 120 min after meals. Results After 12 weeks of treatment, the overall level of glucagon decreased, in which the differences in glucagon levels at 30 min [(220±79) ng/L vs. (203±77) ng/L, P<0.05] and 60 min [(248±119) ng/L vs. (203±82)ng/L, P<0.05] reached significance, respectively, comparing to those before treatment. The area under the curve of glucagon after treatment was significantly lower than that before treatment (438±190 vs. 389 ± 153, P<0.05). In contrast, after treatment, the overall level of C-peptide increased, especially the levels at 30 min [(1.53±1.02) nmol/L vs.(2.03±1.29) nmol/L ], 60 min [(1.93±1.19) nmol/L vs. (2.48±1.75) nmol/L] and 120 min [(2.36±1.47) nmol/L vs. (2.96±1.84) nmol/L], all P<0.05. The area under C-peptide curve increased significantly (3.6±2.2 vs. 4.6±2.9, P<0.05). Fasting plasma glucose, postprandial 2 h plasma glucose and glycosylated hemoglobin A1c were all lower than before, and the differences were statistically significant (P<0.05). Waist circumference and body mass index were significantly lower than before (P<0.05). The amount of insulin used for the treatment decreased by approximately 55.1% compared with that before liraglutide, and the difference was statistically significant (P<0.05). Conclusions Liraglutide inhibits glucagon secretion and lowers blood glucose. It can also reduce body weight, improve islet cell function and reduce insulin use in T2DM.

Effect of high fat diet on proteome in mice stomachs / 生物工程学报

To explore the effect of high fat diet on proteome in mice stomachs, we constructed a model in which the mice were fed with high fat diet as the high fat diet (HFD) group or normal diet as the control (CTRL) group for 110 days. The stomachs were collected and divided into three regions (forestomach (F), corpus (C) and antrum (A)) for protein extraction and mass spectrometry analysis. Of all 9 307 identified proteins in two groups, 4 066 proteins (HFD: 3 832, CTRL: 3 654) were strictly identified by at least one unique peptide and identified twice in three replicates. Using gene ontology (GO) and interaction network analysis we analyzed differentially expressed proteins (fold change≥2) in two groups or between regions. In the whole stomach tissues, proteins up-regulated in HFD group mainly were associated with protein stabilization and protein transport. Differentially expressed proteins between regions showed that forestomach was related to the biological process of keratinization and actin assembly, while corpus and antrum mainly performed digestive function. Compared with forestomach, the corpus and antrum were more affected by the diet. Though there was no significant effect on the basic digestive function of the stomach, proteins that were involved in protein transport and lipid metabolism-related biological processes were significantly highly expressed in HFD group.

Relationship between TSH and pregnancy outcomes during the first half of pregnancy in women / 中华内分泌代谢杂志

[Summary] A total of 352 pregnant women were selected in Affiliated Hospital of Qingdao University. Serum levels of TSH and FT4 were determined and pregnancy outcome were observed in all subjects. According to the standard of American Thyroid Association(ATA) published in 2011 and the Chinese Guideline of Gestation Thyroid Disease published in 2012, the subjects were grouped into control(0. 1≤TSH≤2. 5 mIU/ L), observation(2. 55. 17 mIU/ L)during first-trimester(T1)and control(0. 2≤TSH≤3. 0 mIU/ L), observation(3. 05. 22 mIU/ L) during second-trimester(T2). The results showed that the rupture of membranes, preterm labor, and total obstetrical adverse events in the observation group were significantly higher than those in control group during T1(all P<0. 05), no statistical significance between control group and treatment group. The rupture of membrances in the observation group was significantly higher compared with control group during T2 ( P < 0. 05), no significant difference in other adverse pregnancy outcomes between these two groups. Compared with control group during T1, the proportion of adverse pregnancy outcomes in observation group during T1 was significantly increased(P<0. 05). The elevated TSH is one of the risk factors for the increased incidence of adverse pregnancy outcomes at the first half of pregnancy, especially during T1. L-T4 treatment reduces the incidence of adverse pregnancy outcomes.

Efficacy and influential factors of post-resection 131 I therapy on metastases from differentiated thy- roid carcinoma / 中华核医学与分子影像杂志

Objective To investigate the efficacy and influential factors of post-resection 131 I thera-py in DTC patients with metastases can′t be removed by surgery. Methods A total of 112 DTC patients ( 41 males, 71 females, age range 8-80 years) with metastases from January 2012 to October 2016 in Affil-iated Hospital of Qingdao University were retrospectively analyzed. All patients underwent post-resection 131 I therapy, and the therapeutic effect was assessed. Univariate analysis (χ2 test, rank sum test) and the logis-tic regression analysis were performed to select the influential factors for treatment effect. The ROC curve a-nalysis of significant factors to predict the ineffectiveness of 131 I therapy was performed. Results Patients underwent single or repeated 131I therapy (1-9 times), and the effective rate was 75.89%(85/112). Univa-riate analysis showed that the tumor diameter, the location of metastasis, preablation sTg and sTg/TSH ratio were influential factors for 131 I therapy on metastases(χ2 values:7.187, 15.381;z values:-5.053,-5.187, all P<0.05) . Logistic regression analysis showed that the tumor diameter, preablation sTg were independent influential factors for 131 I therapy ( both P<0.05) . The areas under ROC curve for sTg, sTg/TSH ratio, and tumor diameter to predictive ineffectiveness were 0.824, 0.832, and 0.718, respectively. The cutoff values were 29.825μg/L, 0.298, 3.250 cm, respectively, the sensitivities were 92.60%, 96.30%, 40.70%, and the specificities were 62.40%, 55.30%, 91.80%. Conclusions The therapeutic effect of 131I therapy on metastases from DTC is significant. The longer tumor diameter, the distant metastasis, and the higher preab-lation sTg are negative influential factors for131 I therapy, which could be used to predict the therapeutic effect.

The change of miR-146a in carcinoma tissues and peripheral blood of patients with papillary thyroid carcinoma / 中华内分泌外科杂志

Objective To study the change of miR-146a in the development and progression of papillary thyroid carcinoma(PTC).Methods Real-time fluorescence quantitative polymerase chain reaction was used to detect the change of miR-146a in tumor tissues of 43 cases of PTC and 36 cases of nodular goiter,also in peripheral blood of 32 cases of PTC and 23 cases of nodular goiter.The correlation of miR-146a change and the clinicopathological parameters of patients with PTC was analyzed.Results ① The relative content of miR-146a in the 43 patients with PTC and 36 patients with nodular goiter was 0.0280 ± 0.0131 and 0.0212 ± 0.0111 respectively.The difference had statistical significance (P ＜ 0.05).miR-146a in PTC tissues was significantly correlated to clinicopathological parameters such as lymph node metastasis,tumor stage (P ＜ 0.05),and it was unrelated to age or tumor size(P ＞0.05).② The relative content of miR-146a in peripheral blood of 32 patients with PTC and 23 patients with nodular goiter was 0.0891 ±0.0419 and 0.0922 ±0.0456 respectively.The difference had no statistical significance(P ＞ 0.05).There was no significant correlation between miR-146a in peripheral blood of patients with PTC and age,tumor stage,lymph node metastasis,or tumor size of patients (P ＞ 0.05).Conclusions MiR-146a expression is upregulated in patients with PTC,and there is a significant correlation between miR-146a content and clinicopathological parameters such as lymph node metastasis,tumor stage,especially in advanced stage.It suggests that miR-146a may play a role in carcinogenesis and development of PTC.

The correlation between BRAF mutations, RET/PTC rearrangements and platelet-derived growth factor B expression in papillary thyroid carcinomas / 中华内科杂志

Objective To investigate the prevalence of BRAF T1799A mutation and RET/PTC rearrangement in Qingdao and detect the expression of platelet-derived growth factor B (PDGF-B) in order to investigate the correlation between gene mutation and PDGF-B.Methods Fresh tissue from 48 papillary thyroid carcinomas (PTC) patients was examined for BRAF mutation RET rearrangements (RET/PTC1 and RET/PTC3) by PCR,followed by direct-sequence analysis.The expression of PDGF was analyzed by immunohistochemistry.Results Among the 48 patients,14 (29.2％) were micro PTC; 18 (37.5％) had BRAF T1799A mutations and 23(47.9％) had RET/PTC rearrangement.There were 17 (35.4％) cases of RET/PTC1 and 6 (12.5％) of RET/PTC3,with no multiple rearrangements.Both BRAF T1799A mutation and RET/PTC rearrangement were present in 6 (12.5％) cases of non-micro PTC.The level of PDGF-B expression in BRAF T1799A positive was higher than that in the negative,and the level of PDGF-B expression in RET/PTC3 was higher than that in RET/PTC1 (P ＜ 0.05).The more advanced neoplasm stage was,the stranger PDGF-B expression was.Conclusions The incidence of BRAF T1799A mutation and RET/PTC rearrangement is higher in Qingdao.BRAF T1799A mutation and RET/PTC3 rearrangement in patients suggests a poorer prognosis than the negative one.The BRAF T1799A mutation and RET/PTC3 rearrangement may strengthen the expression of PDGF-B.Both variations suggest a poor prognosis.

Design of human multi-physiological information system / 医疗卫生装备

This paper introduces the structure, components, function and technical design of the multi -physiological information system, which can not only collect but also register and check parameters. The parameters acquired by the system include electrocardiogram, blood pressure, oxygen saturation and pulse.