[Research in evaluation and intervention of cardiovascular complications of patients with type 1 diabetes on demand].

Recently, great progress has been made in the treatment of type 1 diabetes mellitus (T1DM), however the disease still significantly shortens the life expectancy. Cardiovascular complication is the main cause of death in T1DM patients, and the morbidity is even higher than that of type 2 diabetes. The risk factors of cardiovascular complication in T1DM are different from those of type 2 diabetes. Besides hyperglycemia, dyslipidemia, hypertension, microvascular complications and unhealthy lifestyle, non-traditional risk factors also play very important roles in developing cardiovascular complication, such as hypoglycemia, blood glucose variability, insulin resistance, and autoimmune inflammation of heart. At present, there is a lack of risk assessment and prevention measures for cardiovascular complications in T1DM. It is necessary for more studies to explore whether sodium-dependent glucose transporters 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, which can improve cardiovascular and renal outcomes in type 2 diabetes mellitus, can be equally effective in T1DM.

Tannerella forsythia and coating color on the tongue dorsum, and fatty food liking associate with fat accumulation and insulin resistance in adult catch-up fat.

BACKGROUND/OBJECTIVES: We aimed to determine the alteration of Tannerella forsythia and coating color on the dorsal tongue, and fatty food liking in catch-up fat in adult (CUFA), as well as the probable associations between fat accumulation, insulin resistance (IR) and these changes. SUBJECTS/METHODS: T. forsythia on the tongue dorsum, fatty food liking, fat accumulation and insulin sensitivity were investigated in CUFA humans and rats, and tongue-coating color was observed in CUFA individuals. We further determined the changes of fatty food liking, fat accumulation and IR in T. forsythia-infected rodents by oral lavage. RESULTS: Increases in fat accumulation, IR, percentage of subjects with yellow tongue coating and that with T. forsythia detected were observed in CUFA individuals. Additionally, the fat ranking scores were significantly lower and the hedonic ratings of low-fat options of sampled food were lower, while the ratings of high-fat options were remarkably higher in CUFA subjects. Additionally, T. forsythia level elevated in CUFA rats, and fatty food liking, fat accumulation and IR increased in CUFA and T. forsythia-infected animals, with the increases in T. forsythia infection and fatty food liking preceding the occurrence of fat accumulation and IR. CONCLUSIONS: T. forsythia and yellow coating on the dorsal tongue and fatty food liking associate fat accumulation and IR in CUFA. Moreover, we tentatively put forward that T. forsythia, which is very important in yellow tongue-coating microbiota, and its consequent increases in fatty food liking, might be crucial in the development of fat accumulation and IR in CUFA.

Support vector machine-based nomogram predicts postoperative distant metastasis for patients with oesophageal squamous cell carcinoma.

BACKGROUND: We aim to develop effective models for predicting postoperative distant metastasis for oesophageal squamous cell carcinoma (OSCC) for the purpose of guiding tailored therapy. METHODS: We used data from two centres to establish training (n=319) and validation (n=164) cohorts. All patients underwent curative surgical treatment. The clinicopathological features and 23 immunomarkers detected by immunohistochemistry were involved for variable selection. We constructed eight support vector machine (SVM)-based nomograms (SVM1-SVM4 and SVM1'-SVM4'). The nomogram constructed with the training cohort was tested further with the validation cohort. RESULTS: The outcome of the SVM1 model in predicting postoperative distant metastasis was as follows: sensitivity, 44.7%; specificity, 90.9%; positive predictive value, 81.0%; negative predictive value, 65.6%; and overall accuracy, 69.5%. The corresponding outcome of the SVM2 model was as follows: 44.7%, 92.1%, 82.9%, 65.9%, and 70.1%, respectively. The corresponding outcome of the SVM3 model was as follows: 55.3%, 93.2%, 87.5%, 70.7%, and 75.6%, respectively. The SVM4 model was the most effective nomogram in prediction, and the corresponding outcome was as follows: 56.6%, 97.7%, 95.6%, 72.3%, and 78.7%, respectively.Similar results were observed in SVM1', SVM2', SVM3', and SVM4', respectively. CONCLUSION: The SVM-based models integrating clinicopathological features and molecular markers as variables are helpful in selecting the patients of OSCC with high risk of postoperative distant metastasis.

Methylation status of CpG sites in the MCP-1 promoter is correlated to serum MCP-1 in Type 2 diabetes.

AIM: Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine and plays an important role in atherosclerosis of Type 2 diabetes. The aim of this study was to investigate the methylation status of CpG sites in the MCP-1 promoter in Type 2 diabetic patients and its correlation to serum MCP- 1 level, and blood glucose level. METHODS: The 32 patients with Type 2 diabetes and 15 healthy controls were enrolled into the study. Bodymass index, blood pressure, blood lipid, blood glucose, glycosylated hemoglobin (HbA1c), and serum MCP-1 were measured. Genomic DNA was isolated fromthe peripheral blood mononuclear cells (PBMC). Methylation status of CpG sites in theMCP-1 promoter was determined using methylation specific polymerase chain reaction. RESULTS: The promoter region (2890-3050 bp) was predominantly methylated in PBMC from controls.Methylation of CpGmotifs were less methylated in the patients than in the controls (25% vs 80%; p<0.001), while the level of MCP-1 in serum was higher in patients with Type 2 diabetes (193.95±74.96 vs 88.46±55.10; p<0.001). MCP-1 promoter methylation was significantly correlated to serum MCP-1, HbA1c, fasting blood glucose, and triglyceride. CONCLUSION: These data suggest that hypomethylation of CpG sites in the MCP-1 promoter region may be affected by blood glucose and TG, which then increase the serum MCP-1 level and may play a role in the vascular complications of Type 2 diabetes.

Association of the +33371 A/G polymorphism in adiponectin receptor 2 gene with Type 2 diabetes in the Chinese population.

PURPOSE: The aim of this study was to investigate the association between the +33371 A/G polymorphism of adiponectin receptor 2 gene and the risk of Type 2 diabetes (T2DM) in the Chinese population. METHODS: A case-control study was performed among 594 unrelated Chinese people. All of them underwent a standardized assessment on phenotypic characterization including anthropometry, 75-g oral glucose tolerance test with insulin levels, fasting serum total cholesterol, and fasting serum triglyceride. The +33371 A/G polymorphism was detected by PCR-restriction fragment length polymorphism. RESULTS: The PCR products after digestion displayed 3 genotypes, including AA, AG, and GG. The frequencies of AA, AG, and GG genotypes in T2DM group (no.=261) and control group (no.=353) were 0.379, 0.414, 0.207 and 0.162, 0.541, 0.297, respectively. There was a significant difference in both genotypic and allelic frequencies distribution of +33371 A/G polymorphism between T2DM and control subjects (p<0.001). Subjects with AA+AG genotypes showed higher levels of fasting plasma glucose (p=0.024), fasting serum triglycerides (p=0.036), and body mass index (BMI) (p=0.013) than those with GG genotype in the T2DM group but not in the control group. Compared with GG genotype, AA (p<0.001) and AA+AG (p=0.002) genotype group had a significantly higher risk of T2DM, with odds ratio (OR) for 2.290 [95% confidence interval: 1.482-3.359] and 1.963 (1.183-2.997). Compared with AG+GG genotype group, the risk of T2DM in AA genotype increased slightly (p=0.007), with OR for 1.478 (1.025-2.036). CONCLUSION: The present findings suggest that +33371 A/G polymorphism is associated with increased risk of T2DM and multiple insulin resistance-related phenotypes (including fasting plasma glucose, fasting serum triglycerides, and BMI) in the Chinese population.

Effect of the novel triazinium zwitterion 1-methyl-3-phenyl-1,2,4-triazinium-5-olate on immunological responses and experimental brucellosis in mice.

The immunopharmacology of a novel triazinium zwitterion, designated JR-6, was studied in mice. Experiments show dose-response inhibition of antibody and delayed-type hypersensitivity (DTH) responses to sheep red blood cell antigens. Suppression of DTH was confirmed using trinitrochlorobenzene as a contact-sensitizing antigen. Using a model of experimental brucellosis in mice, it was found that JR-6 caused suppression of specific antibody and DTH reaction, as well as spleen weight, but a statistically significant increase in viable counts of Brucella abortus was not observed. Extensive short-term toxicology studies showed reduction in lymphocyte and neutrophil counts, and slow weight gain of treated mice. However, organ histology, liver function tests and biochemical profiles were normal.

Comparative immunopharmacology and toxicology of the bisbenzylisoquinoline alkaloids tetrandrine and berbamine.

Comparison of the bisbenzylisoquinolines tetrandrine and berbamine shows that both drugs are equipotent in terms of enhancement of antibody responses and suppression of delayed-type hypersensitivity (DTH) responses to sheep red blood cell antigens. Both compounds are also equally active when given to mice during the induction and expression phases of DTH. Using a model of experimental brucellosis in mice, it was found that both compounds did not affect antibody responses, while they caused equipotent suppression of DTH. By contrast, berbamine but not tetrandrine caused significant suppression of spleen weight. Also, berbamine caused a significantly greater enhancement of spleen colony counts of Brucella abortus than tetrandrine. Short-term toxicology studies showed no toxic effects at bioactive doses.