The Interaction of GLUT1 and FOXM1 Leads to a Poor Prognosis in Colorectal Cancer.

BACKGROUND: Colorectal Cancer (CRC) is one of the most common fatal diseases with high morbidity. Alteration of glucose metabolism is one of the hallmarks in the development of CRC. Glucose Transporter 1 (GLUT1) is a key rate-limiting protein in hyperactive glucose metabolism and up-regulated in CRC, however, the underlying mechanism of the altered metabolism in CRC is still unknown. METHODS: In this study, immunohistochemical staining was used to evaluate the expression of GLUT1 and FOXM1 in 135 paired CRC and adjacent normal tissues. The association between the expression of GLUT1/FOXM1 and clinicopathological factors was determined and the correlation between GLUT1 and FOXM1 in CRC was investigated. RESULTS: Our results revealed that regardless of tumor location, GLUT1 and FOXM1 were overexpressed in CRC tissues, especially in patients with positive lymph node metastasis and TNM stage III-IV. Furthermore, GLUT1 showed a significantly strong link with FOXM1 in CRC tissue. CONCLUSION: Overexpression of GLUT1 and FOXM1 may play critical roles in CRC leading to a poor prognosis.

A Randomized Controlled Trial to Compare the Effect of Peanuts and Almonds on the Cardio-Metabolic and Inflammatory Parameters in Patients with Type 2 Diabetes Mellitus.

A low carbohydrate diet (LCD), with some staple food being replaced with nuts, has been shown to reduce weight, improve blood glucose, and regulate blood lipid in patients with type 2 diabetes mellitus (T2DM). These nuts include tree nuts and ground nuts. Tree nut consumption is associated with improved cardio-vascular and inflammatory parameters. However, the consumption of tree nuts is difficult to promote in patients with diabetes because of their high cost. As the main ground nut, peanuts contain a large number of beneficial nutrients, are widely planted, and are affordable for most patients. However, whether peanuts and tree nuts in combination with LCD have similar benefits in patients with T2DM remains unknown; although almonds are the most consumed and studied tree nut. This study sought to compare the effect of peanuts and almonds, incorporated into a LCD, on cardio-metabolic and inflammatory measures in patients with T2DM. Of the 32 T2DM patients that were recruited, 17 were randomly allocated to the Peanut group (n = 17) and 15 to the Almond group (n = 15) in a parallel design. The patients consumed a LCD with part of the starchy staple food being replaced with peanuts (Peanut group) or almonds (Almond group). The follow-up duration was three months. The indicators for glycemic control, other cardio-metabolic, and inflammatory parameters were collected and compared between the two groups. Twenty-five patients completed the study. There were no significant differences in the self-reported dietary compliance between the two groups. Compared with the baseline, the fasting blood glucose (FBG) and postprandial 2-h blood glucose (PPG) decreased in both the Peanut and Almond groups (p < 0.05). After the intervention, no statistically significant differences were found between the Peanut group and the Almond group with respect to the FBG and PPG levels. A decrease in the glycated hemoglobin A1c (HbA1c) level from the baseline in the Almond group was found (p < 0.05). However, no significant difference was found between the two groups with respect to the HbA1c level at the third month. The peanut and almond consumption did not increase the body mass index (BMI) and had no effect on the blood lipid profile or interleukin-6 (IL-6).In conclusion, incorporated into a LCD, almonds and peanuts have a similar effect on improving fasting and postprandial blood glucose among patients with T2DM. However, more studies are required to fully establish the effect of almond on the improvement of HbA1c.

The elevated NLR, PLR and PLT may predict the prognosis of patients with colorectal cancer: a systematic review and meta-analysis.

Recently, several studies have reported that inflammatory response and elevated platelet counts may be associated with the poor prognosis of colorectal cancer. This meta-analysis was designed to analyze and evaluate the prognostic role of elevated preoperative or pretreatment neutrophils-to-lymphocytes ratio, platelet-to-lymphocytes ratio or platelet counts in patients with colorectal cancer. We searched PubMed, EMBASE, Cochrane Library and Web of Science to April, 2016. A total of 23 studies (N = 11762 participants) were included for this meta-analysis. Elevated neutrophils-to-lymphocytes ratio have a close relationship with the poor Overall Survival of colorectal cancer with the pooled HR being 1.92 [95% CI 1.57-2.34; P < 0.00001]. This meta-analysis indicated that elevated neutrophils-to-lymphocytes ratio, platelet-to-lymphocytes ratio or platelet counts may be a cost-effective and noninvasive serum biomarker for poor prognosis for patients with colorectal cancer.

Thyroid nodule sizes influence the diagnostic performance of TIRADS and ultrasound patterns of 2015 ATA guidelines: a multicenter retrospective study.

To evaluate the impact of thyroid nodule sizes on the diagnostic performance of thyroid imaging reporting and data system (TIRADS) and ultrasound patterns of 2015 American Thyroid Association (ATA) guidelines. Total 734 patients with 962 thyroid nodules were recruited in this retrospective study. All nodules were divided into three groups according to the maximal diameter (d < 10 mm, d = 10-20 mm and d > 20 mm). The ultrasound images were categorized based on TIRADS and ATA ultrasound patterns, respectively. A total of 931 (96.8%) and 906 (94.2%) patterns met the criteria for TIRADS and ATA ultrasound patterns. The AUC (0.849) and sensitivity (85.3%) of TIRADS were highest in d = 10-20 mm group. However, ATA had highest AUC (0.839) and specificity (89.8%) in d > 20 mm group. ATA ultrasound patterns had higher specificity (P = 0.04), while TI-RADS had higher sensitivity (P = 0.02). In nodules d > 20 mm, the specificity of ATA patterns was higher than TIRADS (P = 0.003). Our results indicated that nodule sizes may influence the diagnostic performance of TIRADS and ATA ultrasound patterns. The ATA patterns may yield higher specificity than TIRADS, especially in nodules larger than 20 mm.

Study on female sexual dysfunction in type 2 diabetic Chinese women.

OBJECTIVE: To investigate the female sexual dysfunction (FSD) in type 2 diabetes patients, by comparing the sexual function between type 2 diabetic women and non-diabetic women with Female Sexual Function Index (FSFI). METHODS: 115 type 2 diabetic women and 107 age-matched non-diabetes women were enrolled with similar backgrounds. Their sexual functions were evaluated with FSFI. Metabolic parameters such as body mass index, blood lipid profile, hemoglobin A1C, plasma glucose were also collected. RESULTS: Total score of FSFI of the type 2 diabetic women were significantly lower than that of the non-diabetic controls (18.27±8.96 vs. 23.02±5.78, P=0.000). Scores of the FSFI domains (desire, arousal, lubrication, orgasm, satisfaction, pain) of the type 2 diabetic group were also lower than those of the control group. According to the FSD criterion (FSFI<25) available in China, the percentage of FSD in the type 2 diabetic group was significantly higher than that of the control group (79.2%vs. 55.0%, P<0.001). These trends seemed more prominent in pre-menopause subgroups. The logistic regression analysis indicated that age and diabetes were independent risk factors of FSD. Body Mass Index (BMI) also had influence in the diabetes group. CONCLUSION: Findings from this study showed that there are more FDS in Chinese type 2 diabetic women than in their non-diabetic counterparts, especially in pre-menopause participants.

Precise microdeletion detection of Prader-Willi Syndrome with array comparative genome hybridization.

OBJECTIVE: Prader-Willi Sydrome (PWS) is a human disorder related to genomic imprinting defect on 15q11-13. It is characterized by a series of classic features such as hypotonia, hyperphagia, obesity, osteoporosis, typical facial and body dysmorphosis, hypogonadism, mental and behaviour disorders. Our study was designed to precisely detect the microdeletions, which accounts for 65%-70% of the PWS. METHODS: Physical and laboratory examinations were firstly performed to diagnose PWS clinically, and to discover novel clinical features. Then the patient was screened with bisulfite-specific sequencing and precisely delineated through high-density array CGH. RESULTS: With the bisulfite-specific sequencing, the detected CpG island in the PWS critical region was found homozygously hypermethylated. Then with array CGH, a 2.22 Mb type II microdeletion was detected, covering a region from MKRN3, MAGEL2, NDN, PWRN2, PWRN1, C12orf2, SNURF-SNRPN, C/D snoRNAs, to distal of UBE3A. CONCLUSIONS: Array CGH, after the fast screening of Bisulfite-specific sequencing, is a feasible and precise method to detect microdeletions in PWS patients. A novel feature of metacarpophalangeal joint rigidity was also presented, which is the first time reported in PWS.

Intracellular retention of human melanocortin-4 receptor: a molecular mechanism underlying early-onset obesity in F261S pedigree of Chinese.

OBJECTIVE: To investigate how F261S mutation identified from Chinese obese patients affects the function of melanocortin 4 receptor (MC4R) and to analyze the obesity-related phenotypes in subjects carrying the F261S mutation. METHODS: F261S mutant of MC4R was generated by site-directed mutagenesis. Plasmids encoding wild-type or F261S mutant of MC4R were transfected into HEK293 and COS-7 cells to examine their functional characteristics. Signaling properties of F261S MC4R were assessed by measuring intracellular cAMP levels in response to alpha-MSH stimulation. Cell surface expression of F261S MC4R was compared with that of wild-type MC4R. Clinical examinations were performed in subjects carrying F261S mutation and in non-mutated controls. RESULTS: The alpha-MSH-stimulated reporter gene activity was significantly reduced in cells expressing F261S MC4R, with a maximal response equal to 57% of wild-type MC4R. The F261S mutation also led to a significant change in the Es50 value compared with the wild-type receptor (P<0.01). Immunofluorescent assay revealed a marked reduction in plasma membrane localization of the MC4R in cells expressing the F261S mutant receptor. The resting metabolic rate and fat composition of the mutant carriers were not significantly different from those of the non-mutated obese controls. CONCLUSIONS: The decreased response to alpha-MSH due to the intracellular retention of MC4R may cause early-onset obesity in the F261S pedigree of Chinese.

Association of KCNJ11 and ABCC8 genetic polymorphisms with response to repaglinide in Chinese diabetic patients.

AIM: The aim of this study was to investigate the association of KCNJ11 E23K and ABCC8 exon16-3T/C with the therapeutic effect of repaglinide in patients with type 2 diabetes. METHODS: A total of 100 Chinese patients with newly diagnosed type 2 diabetes were treated with repaglinide for 24 weeks. Arginine stimulation tests were performed to evaluate beta cell function. Gene variations were detected with PCR-restriction fragment length polymorphism. Responders were defined by a greater than 25% decrease in fasting plasma glucose or a greater than 20% decrease in hemoglobin A1c (HbA1c) values (or both) after the 24 week repaglinide treatment. RESULTS: Both baseline HbA1c and the decrease of HbA1c were significantly higher in patients with E/K and K/K genotypes of the KCNJ11 E23K variant when compared with E/E homozygotes (P=0.0103 and 0.0221, respectively). The decrease in 2 h postprandial plasma glucose (2hPG) was significantly greater in E/K heterozygotes than E/E homozygotes (P=0.0367). There was a significant difference in the response rate to repaglinide treatment between the E and K alleles (68% vs 82%, P=0.0324). The changes in fasting insulin and the homeostasis model assessment of insulin resistance were significantly greater in patients with ABCC8 exon16-3 C/C versus the T/C and T/T genotypes (P=0.0372 and 0.0274, respectively). CONCLUSION: The KCNJ11 E23K variant was associated with the therapeutic effect of repaglinide. In addition, The C/C homozygotes of the ABCC8 exon16-3T/C variant responded better to repaglinide in insulin sensitivity than the T/C and T/T genotypes.

[A novel mutation of WFS1 gene in Chinese patients with Wolfram syndrome].

OBJECTIVE: Wolfram syndrome is an autosomal recessive disorder characterized by early-onset diabetes mellitus, diabetes insipidus, optic atrophy and deafness. The aim of this study was to scan the WFS1 gene mutations in a Chinese Wolfram syndrome pedigree. METHODS: Eight exons and flanking introns of WFS1 gene were screened using PCR-DNA direct sequencing. Effects of the mutation on the structure and function of the WFS1 gene product, Wolframin, were evaluated by bioinformatics. RESULTS: A novel mutation, F417del, in the WFS1 gene was identified. The patient was homozygous of this mutation and the consanguineous parents were heterozygous. The mutation causes the lose of a non-polar amino acid, which was located in the transmembrane domain of the protein product. Bioinformatics predicted that the mutation altered the secondary structure of the transmembrane domain and decreased the hydrophobicity of F417del protein. CONCLUSIONS: This study identified a novel mutation of WFS1 gene and represented the first cause of molecular characterization of Chinese Wolfram syndrome patients.

Resting energy expenditure and its relationship with patterns of obesity and visceral fat area in Chinese adults.

OBJECTIVE: To investigate the relationship between resting energy expenditure (REE) and patterns of obesity/regional fat parameters in Chinese adults. METHODS: Body mass index (BMI), fat mass (FM), fat-free mass (FFM) were assessed in 109 Chinese adults (52 men and 57 women), and their abdominal visceral adipose tissue area (VA) and subcutaneous fat area (SA) were measured using magnetic resonance imaging (MRI) measurements. REE was measured with indirect calorimetry and compared with normal and obese subjects. Multivariate analysis was used to study the factors related to REE. RESULTS: The resting energy expenditure per kilogram of body weight (REE/kg) was closely related with the area of abdominal visceral fat measured with MRI. REE/kg was significantly lower in overweight/obesity subjects than in normal-weighted subjects, and significantly lower in subjects with abdominal obesity (VA > or = 100 cm2) than in subjects with non-abdominal obesity (VA < 100 cm2, BMI > or = 25 kg/m2). In the stepwise regression analysis of REE/kg on regional fat parameters, VA in men and women and SA in women were independent factors reversely related to REE/kg. CONCLUSION: REE/kg is associated with the visceral fat area and more prominent in men. REE/kg can be used as an index in the pathophysiology of intra-abdominal obesity.

[Cloning and functional analysis of melanocortin 4 receptor mutation gene F261S].

OBJECTIVE: To evaluate the function change of the melanocortin 4 receptor (MC4R) protein with mutation of F261S. METHODS: Human embryonic cells of the HEK293 line were cultured. Wild-type genomic DNA and F261S mutation human melanocortin 4 receptor genes from the genomic DNA of aproband of homozygotic F612 mutation were amplified and cloned into a topo-TA eukaryotic expression plasmid vector. After the wild-type and F261S mutated proteins were expressed in HEK293 cells, alpha-MSH (10(-11) approximately 10(-5) mmol/L) was added, then the intracellular cAMP was detected with dual luciferase reporter assay system. RESULTS: When the concentration of alpha-MSH added was 10(-9) approximately 10(-8) mmol/L, the intracellular alpha-MSH concentration of the cells transfected with wild-type MC4R gene was significantly higher than that of the cells transfected with F261S mutation gene (P < 0.05). When the concentration of alpha-MSH added went to 10(-7) approximately 10(-5) mmol/L, the differences became even more significant (all P < 0.01). CONCLUSION: The novel MC4R mutation F261S undermines the signal transduction. It may be the possible reason leading to monogenic mutation obesity in Chinese.