TRIIODOTHYRONINE ACTIVATES GLYCEROL-3-PHOSPHATE ACYLTRANSFERASE 3 VIA AGGTCA-LIKE-DIRECT-REPEAT-4 TYPE THYROID HORMONE RESPONSE ELEMENT.

BACKGROUND: Thyroid hormone participates in lipid metabolism regulation. However, the effects on triacyleride or triacylglycerol metabolism are complex and not fully clarified yet. In this study, we try to identify novel thyroid hormone-targeting lipogenic metabolic genes and analyze their molecular regulative mechanism. METHOD: Thirty-five promoters of twenty-nine human lipogenic regulative enzyme genes were constructed into pXP1 luciferase reporter plasmid (PFK2/FBP2-luc) and transfected into HeGP2 cells, respectively. Gene expression induced by triiodothyronine (T3) was detected by luciferase assay. The T3-activated gene promoter was then analyzed by sequence analysis, deletion and mutation, and electrophoretic mobility shift assay (EMSA). RESULTS: After 10 nM T3 stimulation for 36 h, phosphogluconate dehydrogenase, malic enzyme, Glycerol-3-phosphate acyltransferase (GPAT) 3, and 1-acylglycerol-3-phosphate O-acyltransferase (AGPAT) 2 were significantly activated, respectively. A AGGTCA-like-direct-repeat-4 consensus thyroid hormone response element (DR4-TRE)-like sequence was found in the GPAT3 promoter, which was then verified to be necessary for T3-induced GPAT3 activation by gene deletion and mutation analysis. EMSA further identified that T3-thyroid receptor (TR) α-retinoid-X receptor (RXR) complex directly bound on the GPAT3 promoter. CONCLUSION: Triiodothyronine could activate the GPAT3 through DR4-TRE-like sequence binding to participate in lipogenic regulation. AGPAT2 may be another thyroid hormone target enzyme.

[Effect of preoperative serum alanine aminotransferase and asparagine aminotransferase ratio on prognosis of patients with gastric cancer].

Objective: To study the relationship of liver function index alanine aminotransferase and aspartate aminotransferase ratio (LSR) with clinicopathological factors in patients with gastric cancer and its clinical significance in predicting the survival of patients. Methods: A retrospective case-control study was used. Retrospective analysis was conducted on 891 patients with advanced gastric cancer who underwent gastric cancer surgery at the Gastrointestinal Surgery Department of Harbin Medical University Cancer Hospital from January 2007 to December 2010, having complete postoperative clinicopathological and follow-up data. Case inclusion criteria: (1) preoperative definite diagnosis of gastric cancer, residual gastric cancer and other gastric tumors were excluded; (2) no neoadjuvant therapy before surgery; (3) no other serious diseases such as acute coronary heart disease, cirrhosis, chronic renal failure, etc.; (4) radical gastrectomy was performed, palliative treatment or open laparotomy cases were excluded; (5) complete postoperative pathological data, complete follow-up information; (6) cause of death was associated with gastric cancer. Blood examination was performed during hospitalization. The best cut-off points of LSR, hemoglobin, lymph node metastasis rate, maximum diameter of tumors, alkaline phosphatase, glutamyl transpeptidase, total bilirubin and lactate dehydrogenase were obtained by using receiver operating characteristic curve(ROC). Patients were divided into two groups according to best LSR cut-off points. The relationship between LSR and clinicopathological factors was analyzed, and the overall survival rate of different LSR groups was compared. Relevant clinical factors and LSR were included in the univariate and multivariate survival analysis using the Cox method. Results: The best cut-off point of LSR in ROC curve was 1.43, and 682 cases in LSR<1.43 group, 209 cases in LSR≥1.43 group. The best cut-off points of hemoglobin, lymph node metastasis rate, maximum diameter of tumors, alkaline phosphatase, glutamyl transpeptidase, total bilirubin and lactate dehydrogenase were 130.2 g/L, 18.0%, 4.75 cm, 68.1 U/L, 16.55 U/L, 5.58 µmol/L and 135.8 U/L, respectively. Between patients with LSR<1.43 and LSR≥1.43, age (χ(2)=4.412, P=0.036), depth of tumor invasion (χ(2)=64.306, P<0.001), histological type (χ(2)=8.026, P=0.005), alkaline phosphatase (χ(2)=8.217, P=0.004), glutamyl transpeptidase (χ(2)=33.207, P<0.001), total bilirubin (χ(2)=14.012, P<0.001) and lactate dehydrogenase (χ(2)=63.630, P<0.001) were significantly different. The 1-, 3- and 5-year survival rates of LSR<1.43 group and LSR≥1.43 group were 70.8%, 31.3%, 25.0% and 64.9%, 24.4%, 11.3% respectively, whose difference was significant (χ(2)=10.140, P=0.001). Univariate analysis showed that age, hemoglobin, TNM stage, depth of invasion, lymph node metastasis rate, lymph node metastasis, histological type, maximum diameter of tumors, glutamyl transferase, total bilirubin and LSR were associated with overall survival of gastric cancer (all P<0.05). Multivariate analysis showed that tumor TNM stage (HR=1.605, 95%CI: 1.332 to 1.936, P<0.001), tumor invasion depth (HR=1.299, 95%CI: 1.168 to 1.445, P<0.001), lymph node metastasis rate (HR=2.400, 95%CI:1.873 to 3.076, P<0.001), lymph node metastasis (HR=1.263, 95%CI: 1.106 to 1.478, P=0.007), maximum tumor diameter (HR=1.375, 95%CI: 1.134 to 1.669, P=0.001), and LSR (HR=1.427, 95%CI: 1.190 to 1.711, P<0.001) were independent risk factors for the prognosis of patients with gastric cancer. Conclusions: LSR is an independent risk factor for the prognosis of gastric cancer patients, and the detection is simple and easy. It is a potential marker for the prognosis of gastric cancer. Therefore, in the preoperative comprehensive management stage, it should be possible to restore and improve the liver function in order to obtain a better prognosis of gastric cancer and prolong the survival time of patients.

[Relationship between body mass index and clinicopathological characteristics and prognosis of gastric cancer patients].

Objective: To investigate the relationship between body mass index (BMI) and clinicopathological characteristics and prognosis of gastric cancer patients. Methods: The clinical data of 788 patients with advanced gastric cancer were retrospectively analyzed. According to WHO weight standard, BMI<18.5 kg/m(2) was the low weight group, BMI 18.5~< 25.0 kg/m(2) was the normal weight group, BMI ≥ 25.0 kg/m(2) was the overweight group. The low weight group included 127 cases, the normal weight group included 540 cases and the overweight group included 121 cases. The relationship between different BMI groups and clinicopathological characteristics of patients was analyzed. Cox multivariate regression model was used to analyze the independent factor of the prognosis of patients. Results: The average BMI of 788 patients was 21.70 kg/m(2). The patients' BMI was significantly correlated with depth of invasion, maximum diameter of tumors, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) (all P<0.05). BMI was marginally correlated with gender, age, smoking, alcohol consumption, TNM stage, lymph node metastasis and histological type (all P>0.05). Furthermore, BMI was significantly correlated with prealbumin, prognostic nutritional index, total protein, albumin and hemoglobin levels (all P<0.05). BMI was also significantly correlated with intraoperative bleeding volume, operation time, number of lymph node resection, number of lymph node metastasis and lymph node metastatic ratio (all P<0.05). The median survival time of the entire group was 35.3 months. The median survival time of patients in low weight group, normal weight group, and overweight group was 21.0 months, 26.3 months, and 31.2 months, respectively, the differences were statistically significant (P<0.001). Cox multivariate analysis showed that TNM stage, depth of tumor invasion, lymph node metastasis, PLR and BMI were independent risk factors of the prognosis of patients with gastric cancer (all P<0.05). Conclusions: BMI is associated with the nutritional status, intraoperative blood loss, operative time, and lymph node metastatic ratio of patients with gastric cancer. BMI is an independent risk factor of the prognosis of patients with gastric cancer. The overall survival time of patients with low body weight is shorter than those of normal weight and overweight patients.

The surgical treatment of isolated left-sided hepatolithiasis: a 22-year experience.

BACKGROUND: Various therapeutic methods are used in isolated left hepatolithiasis (ILH), and long-term results are not as satisfactory as they should be. METHODS: A retrospective analysis of 128 patients with ILH who were treated in our center over the last 22 years was undertaken to address patient age, gender, preoperative evaluation, operative findings, treatment modalities, and postoperative courses. RESULTS: Sixty of the 128 patients were male and 68 were female, with a mean age of 42 years (range, 16-72 years). Among these patients, most (81%) had stones in both left external hepatic duct (LEHD) and left medial hepatic duct; in contrast 13 patients (10%) had stones only in the LEHD, and 7 patients (6%) had stones only in the left hepatic duct. Concomitant strictures were present in the left hepatic duct, left medial hepatic duct, and LEHD in 60%, 76%, and 82%, respectively, most of which were severe. When compared with left lateral segmentectomy, left hepatic lobectomy had a lower rate of residual stones (4% vs 22%; P < .01). Residual/recurrent stones and ductal strictures were the 2 most common causes that affected the long-term results. Before June 1996, left lateral segmentectomy was performed more frequently than left hepatic lobectomy (59% vs 12%; P < .01); after June 1996, left hepatic lobectomy was performed more frequently (77% vs 13%; P < .01). Although there were no differences in length of operation, intraoperative bleeding, and postoperative complications, residual stones were more common after left lateral segmentectomy. CONCLUSIONS: Left hepatic lobectomy appears to be the most effective treatment for selected patients with ILH, if other operative procedures cannot remove all the related lesions, which include stones, dilation, stricture, or potential cholangiocarcinoma.

Surgical treatment of biliary ductal stricture complicating localized left hepatolithiasis.

AIM: To summarize the experience in the clinical treatment of biliary duct strictures complicating localized left hepatolithiasis in the last two decades. METHODS: A retrospective analysis of 67 cases of biliary duct strictures complicating localized left hepatolithiasis treated in our center in the last two decades was made with regards to each patient's age, gender, results of various preoperative examinations, operative findings, treatment and postoperative courses. RESULTS: The incidence of left hepatic duct (LHD) stricture was 59.8% and that of a left external hepatic duct (LEHD) stricture was 84.0 % and 84.8% respectively, in which a severe degree dominated. Among the operative procedures used in the treatment of LHD strictures, plastic operation plus biliary enteric anastomosis ranks first in frequency (52.2%), with a re-stricture rate of 17.1%. Left lobectomy ranks third (19.4%) with no re-stricture. Simple plastic performance or dilation had a high occurrence rate of re-stricture and usually needed subsequent surgery. Most LEHD strictures were eradicated by lateral segmentectomy or lobectomy, whereas most LMHD strictures were just the opposite. The rate of preoperative diagnosis of LMHD by endoscopic retrograde cholangiography, percutaneous transhepatic cholangiography, computed tomography or intraoperative and postoperative trans-T-tube cholangiography was much lower than that of LEHD or extrahepatic duct. CONCLUSION: Too much attention paid to LEHD disorders in the treatment of localized left hepatolithiasis potentially results in negligence or omission in LMHD disorders. Malpractice treatments of LHD strictures are important factors affecting the long term results of localized left hepatolithiasis, for which left lobectomy is usually the therapy of choice.

Protective effect of vitamin E on age-related alterations of Kupffer cell energy metabolism.

AIM: To investigate the mechanism of age-related reduction of Kupffer cell (KC) phagocytic capacity and the protective management. METHODS: Using rhodamine 123 fluorescence density and rate of glucose utilization as parameters, we measured the mitochondrial energy metabolism status in vitro and the glucose utilization capacity of isolated rat liver Kupffer cells (KCs) from rats of various ages (6 mo, 12 mo, 18 mo and 24 mo) and the effect of vitamin E (VE) pretreatment (500 mg/kg/wk × 13 wk). RESULTS: The rate of KC glucose utilization and the rhodamine fluorescence density of KC mitochondria of 18 mo-old untreated rats (NVEG) were significantly lower than that of 6 mo-old NVEG by 19.3% (4.0 nmol·h ± 0.4 nmol·h(-1) 10.6 cells(-1) vs 5.7 nmol·h ± 0.6 nmol·h(-1) 10(6) cells(-1), P < 0.05) and 19.5% (80.5 ± 6.3 vs 100.0 ± 4.7, P < 0.01) respectively; Rate of KC glucose utilization and the rhodamine fluorescence density of KC mitochondria of 6 mo-old rats were also lower than the 24 mo-old NVEG by 35.1% (3.7 nmol·h ± 0.6 nmol·h(-1)10(6) cells(-1) vs 5.7 nmol·h ± 0.6 nmol·h(-1) 10(6) cells(-1), P < 0.01) and 32.1% (67.9 ± 7.4 vs 100.0 ± 4.7, P < 0.01) respectively. The two parameters of 18 mo-old VE pretreated rats (VEG) were significantly higher than those of 18 mo-old NVEG, and statistically comparable to those of 6 mo-old VEG. The two parameters of the 24 mo-old VEG were significantly higher in comparison with those of 24 mo-old NVEG, but still significantly lower than those of 6 mo-old VEG. CONCLUSION: Aging has a significantly negative effect on KC energy metabolism, which can be alleviated by VE pretreatment.

[Surgical treatment for hilar bile duct stricture].

474 patients suffering from hilar bile duct strictures were treated from 1975 to 1992. 74.7% of the patients had a history of biliary surgery for 1-5 times. Causes of strictures were of iatrogenic in 10.9%, of primary in 71.7%, and of suppurative in 7.1%. Site of strictures: LHD in 37.6%, LHD+RHD+CHD in 17.4%, RHD in 9.6%, CHD in 14.7%, and LHD+RHD in 11.5%. The inferior end of the CBD were of spasmodic or flaccid in 23.6% and 48.3%, respectively. Treatment included cholangioplasty in 56.5%, dilatation and stent in 15.2%, lobectomy and segmetectomy of involued liver in 48%, repairing in 11.4%, bilio-enterostomy in 60.7%, and portal vein decompression in 6.3%.

A model of reversible obstructive jaundice in the rat.

A model of reversible, extrahepatic biliary obstruction is described. Vessel loop blockade of the biliary tree results in obstructive jaundice while removal of the exteriorized vessel loop provides internal biliary drainage without subsequent laparotomy. This technique combined with a system for chronic venous infusion and arterial blood sampling in the unrestrained rat is ideal for long-term metabolic studies of obstructive jaundice. Male Fisher 344 rats (275-350 g) underwent either the combined procedure of total biliary tract blockade and vascular access or sham operation. Mean serum bilirubin was significantly elevated (12.7 +/- 8.9 mg/dl) in the experimental group and following relief of biliary obstruction significantly dropped below 1 mg/dl in all animals except one. Concomitant changes in alkaline phosphatase, glutamate oxaloacetate transaminase, and glutamate pyruvate transaminase were seen. Experimental and control rats initially lost weight following laparotomy; however, mean body weight stabilized by the 5th postoperative day and was similar in both groups on the 10th postoperative day. This combined procedure is a simple, effective and reproducible method of obstructive jaundice.