Liyong Zhu

High-intensity focused ultrasound treatment for patients with unresectable pancreatic cancer

BACKGROUND High-intensity focused ultrasound (HIFU) is a non-invasive method of solid tissue ablation therapy. However, only a few studies have reported the effect of HIFU for unresectable pancreatic cancer. This study aimed to evaluate the clinical benefits, survival time and complications associated with the use of HIFU ablation in patients with unresectable pancreatic cancer. METHODS Twenty-five patients with unresectable pancreatic cancer were enrolled in our study. All patients received HIFU therapy for tumors at least once. The therapeutic effects of HIFU was evaluated in terms of Karnofsky performance status (KPS) scores, pain relief, serum CA19-9, and imaging by B-US and CT before and after the therapy. We also recorded median overall survival time and complications caused by the treatment. RESULTS In the 25 patients, KPS scores were above 60, and increased KPS was observed in 23 patients after treatment. Pain relief occurred in 23 patients. Serum CA19-9 levels were significantly reduced one month after HIFU treatment and became negative in 5 patients. B-US revealed enhanced tumor echogenicity in 13 patients and decreased tumor blood supply in 9. Tumor necrosis was confirmed by CT in 8 patients one month after HIFU treatment. The median overall survival time was 10 months, and the 1-year survival rate was 42%. No severe complications were observed after HIFU treatment. CONCLUSION HIFU can effectively relieve pain, increase KPS, decrease tumor growth and prolong the survival time of patients with unresectable pancreatic cancer.

Can low BMI Chinese patients with type 2 diabetes benefit from laparoscopic Roux-en-Y gastric bypass surgery? ☆

BACKGROUND The efficacy of laparoscopic Roux-en-Y gastric bypass (LRYGB) in type 2 diabetes mellitus (T2D) is closely associated with the preoperative body mass index (BMI) of the patient. There is a lack of long-term and large sampling evidence on the efficacy of LRYGB in T2D patients with low BMI in China. OBJECTIVES This retrospective study aimed to evaluate the efficacy of surgical treatment in a Chinese population with T2D (especially patients with BMI<27.5 kg/m2). SETTING University-affiliated hospital, China METHODS: Seventy-eight patients with T2D were included in the study and evaluated before and after LRYGB surgery. No patients were lost to follow-up at any time points. RESULTS Thirty-eight T2D patients with BMI≥27.5 kg/m2 in group 1 (high BMI group) had significant improvements in waist circumference, blood glucose levels, homeostasis model assessment-insulin resistance index, and C-peptide levels after LRYGB (P<.05). Forty T2D patients with BMI<27.5 kg/m2 in group 2 (low BMI group, including 19 T2D patients with BMI<25 kg/m2) had significant improvements in waist circumference and waist-to-hip ratio after LRYGB (P< .05). CONCLUSIONS LRYGB surgery may be beneficial in T2D patients with BMI<27.5 kg/m2 in China.

The role of foregut exclusion in the deterioration of glucose and lipid metabolism induced by a high-fat diet

AIM The small intestine may be involved in the improvement of glucose and lipid metabolism after bariatric surgery; however, the role of the foregut in metabolic changes remains unclear. This study used normal rats fed a high-fat diet (HFD) after bariatric surgery to determine the role of the foregut in glucose and lipid metabolism. METHODS Duodenum-jejunum bypass (DJB), gastrojejunostomy (GJ) and sham-operations were performed on Sprague-Dawley (SD) rats. Oral glucose tolerance, insulin sensitivity, β-cell function, lipid profile, glucose-stimulated glucose-dependent insulinotropic polypeptide (GIP) levels and glucagon-like peptide-1 (GLP-1) levels were measured. The rats were observed for 24 weeks post-surgery. RESULTS Food intake and body weight were similar between the groups during the study period (P>0.05). The DJB group exhibited better glucose and lipid metabolism than the other groups (P<0.05). Compared with the GJ group, the DJB group demonstrated superior oral glucose tolerance, insulin sensitivity and lipid profiles (P<0.05); β-cell function in the two groups was similar (P>0.05). The GIP levels were decreased in the DJB group and increased in the GJ group (P<0.05), and the GLP-1 levels were increased in the DJB and GJ groups (P>0.05). CONCLUSIONS We found that foregut exclusion can prevent disordered glucose and lipid metabolism. Additionally, decreased GIP secretion was associated with improvements in glucose tolerance and insulin sensitivity, particularly related to lipid metabolism. Increased GLP-1 benefited β-cell function; however, it could not reverse the disordered glucose and lipid metabolism induced by a HFD.

The role of visceral adipose tissue on improvement in insulin sensitivity following Roux-en-Y gastric bypass: a study in Chinese diabetic patients with mild and central obesity

Abstract Background Most Chinese patients with type 2 diabetes mellitus (T2DM) have mild obesity and central obesity. Central obesity is combined with insulin resistance. The aim of this study was to assess the effect of abdominal adipose tissue on insulin-sensitivity improvement after Roux-en-Y gastric bypass (RYGB) in Chinese diabetic patients with mild and central obesity. Methods Seventeen T2DM patients with a mean body mass index of 30.3 kg/m2 were scheduled for laparoscopic RYGB. A hyperinsulinemic-euglycemic clamp and dual-energy X-ray absorptiometry were performed prior to surgery and 3 months after RYGB. The primary end points were the correlations between insulin sensitivity and abdominal adipose tissue, including visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), before and 3 months after RYGB. Results Indices of peripheral insulin sensitivity, including glucose-disposal rate (M value) and glucose infusion rate, were significantly increased after RYGB. Body-fat mass, VAT and SAT were significantly reduced after RYGB. The pre-operative M value was significantly correlated with VAT mass (r = –0.57, P = 0.02), but not correlated with SAT mass. M value changes after RYGB were highly correlated with changes in VAT mass (r = –0.59, P = 0.01), percentage of VAT mass (r = –0.66, P < 0.01), VAT area (r = –0.56, P = 0.02) and percentage of VAT area (r = –0.57, P = 0.02). Conclusions A significant correlation was observed between increased peripheral insulin sensitivity and decreased VAT following RYGB in Chinese patients with mild and central obesity. VAT and SAT were significantly decreased with improved insulin sensitivity after RYGB. VAT mass may be considered as an indication for gastric bypass during patient selection.

Farnesoid X Receptor (FXR) Interacts with Camp Response Element Binding Protein (CREB) to Modulate Glucagon-Like Peptide-1 (7–36) Amide (GLP-1) Secretion by Intestinal L Cell

BACKGROUND/AIMS Type II diabetes is a complex, chronic, and progressive disease. Glucagon-like peptide-1 (7-6) amide (GLP-1) is a gut hormone released from the L cells which stimulates insulin secretion, and promotes insulin gene expression and β-cell growth and differentiation. Elevated levels of hormone secreted by L cells are an important reason for diabetes improvement. GLP-1 secretion has been reported to be regulated by farnesoid X receptor (FXR), a transcriptional sensor for bile acids which also acts on glucose metabolism. Herein, we attempted to evaluate the effect of FXR on GLP-1 secretion in mouse enteroendocrine L cell lines, STC-1 and GLUTag, and to investigate the underlying mechanism. METHODS ELISA and Western blot assays were employed to examine the levels of GLP-1 and FXR, and the effect of FXR on GLP-1 secretion; online database, including BioGRID and KEGG were used to identify the potential interactions between FXR and proteins and involved pathways; GST pull-down and Co-Immunoprecipitation (Co-IP) assays were performed to validate FXR-CREB interaction; Luciferase reporter gene assays were used for CREB transcriptional activity determination. RESULTS FXR inversely regulated GLP-1 secretion in the mouse enteroendocrine L cell lines, GLUTag and STC-1. A total of 24 nonredundant human proteins were shown to be related to FXR by BioGRID; KEGG pathway analysis showed that FXR was related to glucagon signaling pathway, particularly with the transcriptional activators CREB, PGC1α, Sirt1 and CBP. CREB could positively regulate GLP-1 secretion in GLUTag and STC-1 cells. FXR combined with CREB to inhibit its transcriptional activity, thus inhibiting proprotein convertase subtilisin/ kexin type 1 (PCSK1) protein level and GLP-1 secretion. CONCLUSION In the present study, we demonstrated a negative regulation of GLP-1 secretion by FXR in L cell lines, GLUTag and STC-1; FXR exerts its function in L cells through interacting with CREB, a crucial transcriptional regulator of cAMP-CREB signaling pathway, to inhibit its transcriptional activity. Targeting FXR to rescue GLP-1 secretion may be a promising strategy for type II diabetes.

Correlation analysis between eGFRcys and SXscore in patients with diabetes.

The aim of the present study was to explore the association between the cystatin C-based estimated glomerular filtration rate (eGFRcys) and the SYNTAX score (SXscore) in patients with diabetes. To the best of our knowledge, this correlation has not been reported previously. The eGFRcys and SXscore from 612 consecutive patients with diabetes were retrospectively included in this study. The patients were angiographically diagnosed with coronary artery disease (CAD) between July 2010 and March 2012 at the Department of Endocrinology. The SXscore was calculated using a previously described SXscore algorithm. Pearson correlations were used to analyze the correlation between eGFRcys and SXscore. Patients with renal dysfunction were older, more often female and more likely to have a history of hypertension when compared with those with normal renal function. The eGFRcys values were significantly lower and the cystatin C levels were significantly higher in the highest SXscore group than those in other groups (P<0.001). Correlation analysis indicated that eGFRcys was negatively correlated with the SXscore (r=−0.7918, P<0.001). In addition, a significantly positive correlation was identified between levels of cystatin C and the SXscore (r=0.8891, P<0.001). In conclusion, eGFRcys is an independent predictor of SXscore in patients with diabetes. The eGFRcys-estimating method may be considered important in the assessment of the SXscore in patients with diabetes.