Liver-adipose tissue crosstalk: A key player in the pathogenesis of glucolipid metabolic disease / 中国结合医学杂志

Glucolipid metabolic disease (GLMD), a complex of interrelated disorders in glucose and lipid metabolism, has become one of the leading chronic diseases causing public and clinical problem worldwide. As the metabolism of lipid and glucose is a highly coordinated process under both physiological and diseased conditions, the impairment in the signals corresponding to the metabolism of either lipid or glucose represents the common mechanism underlying the pathogenesis of GLMD. The liver and adipose tissue are the major metabolic organs responsible for energy utilization and storage, respectively. This review article aims to summarize the current advances in the investigation of the functional roles and the underling mechanisms of the interplay between the liver and adipose tissue in the modulation of GLMD development. Fibroblast growth factor 21 (FGF21) and adiponectin represent the two major hormones secreted from the liver and adipose tissues, respectively. FGF21 exerts pleiotropic effects on regulating glucose and lipid homeostasis majorly through inducing the expression and secretion of adiponectin. Therefore, FGF21-adiponectin axis functions as the key mediator for the crosstalk between the liver and adipose tissue to exert the beneficial effects on the maintenance of the homeostasis of energy consumption. The liver- and adipose tissue-derived factors with pleiotropic effects on regulating of lipid and glucose metabolism function as the key mediator for the crosstalk between these two highly active metabolic organs, thereby coordinating the initiation and development of GLMD.

Hypoadiponectinemia predicts impaired endothelium-independent vasodilation in newly diagnosed type 2 diabetic patients: an 8-year prospective study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic properties. The aim of this study was to investigate whether low adiponectin levels predict the impairment of endothelial function in newly diagnosed type 2 diabetic patients in an 8-year prospective study.</p><p><b>METHODS</b>In the prospective study, we enrolled 133 newly diagnosed type 2 diabetic patients without subclinical atherosclerosis and gave them intensive therapy; the mean treatment period was 8 years. Intensive treatment was a stepwise implementation of behavior modification and pharmacological therapy targeting hyperglycaemia, hypertension, dyslipidaemia and obesity. We measured baseline circulating adiponectin with an enzyme-linked immunosorbent assay, endothelium-dependent and -independent vasodilation by high-resolution vascular ultrasound. At year 8, 102 patients were reexamined for endothelium-dependent and -independent vasodilation.</p><p><b>RESULTS</b>Sex-adjusted adiponectin level was positively correlated with endothelium-independent vasodilation both at baseline (r = 0.150, P = 0.043) and at year 8 (r = 0.339, P = 0.001), whereas no association was found between adiponectin and endothelium-dependent vasodilation. In a stepwise multivariate linear regression model, adiponectin was an independent predictor for impaired endothelium-independent vasodilation at year 8 (P = 0.001).</p><p><b>CONCLUSIONS</b>Plasma adiponectin concentration was associated with endothelium-independent vasodilation and hypoadiponectinemia predicted the impairment of endothelium-independent vasodilation in newly diagnosed type 2 diabetic patients under multifactorial intervention. These data support the causative link of impairment of endothelium-independent vasodilation with hypoadiponectinemia.</p>

Alginate-barium sulfate microspheres via vascular interventional procedures in treatment of VX2 tumor-bearing rabbits / 第二军医大学学报

Objective: To study the therapeutic effect of alginate-barium sulfate microspheres via transcatheter hepatic arterial infusion in treatment of liver VX2 tumors in rabbits. Methods: A total of 24 rabbits were randomly divided into 3 groups, with 5 rabbits in group A (normal control group); 19 rabbits implanted with liver VX2 turnors were further divided into 2 groups, with 10 rabbits in group B (tumor control group) , and 9 in group C (therapy group). Rabbits in group C were catheterized with 3F microcatheter by Seldinger technique for interventional therapy. Spiral CT scanning was performed in group B and group C 14 days after implantation and 14 days after treatment. Liver function tests (TB, ALT, and AST) were performed before and 7 days after treatment. Five rabbits in group B and C were sacrificed to measure the tumor weight and volume; MVD and expression of CD34 and VEGF expression were examined by immunohistochemical technique. Survival periods of the animals were observed and animals were sacrificed 70 days after treatment. Results: Seven days after treatment, the ALT and AST in group B were significantly higher than those in group A and group C (P<0.01). Fourteen days after treatment, the average tumor weights in group C was significantly lower than that in group B ([2.434±0.992] g vs [4.696± 1.2461 g, P<0.01); and the tumor volume in group C was also significantly lower than that in group B ([2.126±0.929] cm3 vs [3.962±1.101] cm3, p< 0.01). Pathological examination showed large necrotic areas in the tumors in group C. CD34 stained necrotic area had no obvious microvessels. The angiogenesis was decreased greatly in the tumor tissues left. Weak VEGF expression was only found in the survived tumor cells. In contrast, group B had abundant cancer cells, large cancerous nests, abundant CD34 positive angiogenesis and strong cytoplasmic staining of VEGF. The survival of rabbits in group C was obviously longer than in group B. Conclusion: Treatment with alginate-barium sulfate microsphere via hepatic artery infusion is safe and feasible for treating liver VX2 tumor. Alginate-barium sulfate microspheres can obviously inhibit tumor growth and have less toxicity to the normal liver tissue.

Adenovirus-mediated overexpression of AMP-activated protein kinase induces LX2 cell apoptosis / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of adenovirus-mediated overexpression of AMP-activated protein kinase (AMPK) on apoptosis of hepatic stellate cell line LX2.</p><p><b>METHODS</b>After adenovirus infection of the LX2 cells, the exogenous gene expression was detected by Western blotting, and cell apoptosis evaluated by flow cytometry with PI staining. Agarose gel electrophoresis was performed to detect the DNA ladder, and the expressions of caspase-3, Bcl-2 and Bax are detected by Western blotting.</p><p><b>RESULT</b>With AMPK overexpression, apoptotic peak and DNA ladder of the infected cells appeared, and pro-caspase-3 was activated to transform into caspase-3 accompanied by up-regulated Bax expression, whereas Bcl-2 expression was hardly detectable by Western blotting.</p><p><b>CONCLUSION</b>Overexpression of AMPK mediated by the adenovirus can induce LX2 cell apoptosis, possible as a result of up-regulated Bax expression with low Bcl-2 expression.</p>

Antitumour effects on human colorectal carcinomas cells by stable silencing of phospholipase C-gamma 1 with lentivirus-delivered siRNA / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>In most colorectal carcinomas, the level of phospholipase C (PLC)-gamma 1 expression is greatly elevated. Increased expression of PLC-gamma 1 may play an important role in colon carcinogenesis, but the mechanism is not well known. The aim of this study was to evaluate the role of PLC-gamma 1 in colon carcinogenesis by using recombinant lentivirus that stably suppressed the PLC-gamma 1 expression in human colorectal carcinoma LoVo cells.</p><p><b>METHODS</b>Recombinant lentivirus producing PLC-gamma 1 siRNA were prepared. After LoVo cells were transduced by each lentivirus, stably transduced cells were selected by Blasticidin. The protein and mRNA expression of PLC-gamma 1 were examined by Western-blot and reverse transcription-polymerase chain reaction (RT-PCR) analysis, and the effects of the lentivirus on the cell adhesion, migration and apoptosis were analyzed.</p><p><b>RESULTS</b>Stable LoVo cell line deficient in PLC-gamma 1, was established. Notably, PLC-gamma 1 was silenced without affecting the levels of other subtypes of PLC so that the role of PLC-gamma 1 in colon carcinogenesis could be examined. Silencing of endogenous PLC-gamma 1 resulted in efficient inhibition of the adhesion and migration of LoVo cells in vitro and a great increase of 5-fluorouracil induced apoptosis (30%-40%) of LoVo cells.</p><p><b>CONCLUSIONS</b>PLC-gamma 1 may play an important role in metastasis and anti-apoptosis in human colorectal carcinomas.</p>

Emergent treatment of severe traumatic intracranial hematoma with minimally invasive technique / 中华急诊医学杂志

Objective To evaluate the value of minimally invasive technique in treatment of severe traumatic intracranial hematoma at emergency department.Method From January 1995 to December 2005,126 patients were treated by using the minimally invasive technique in Affiliated Chaoyang hospital once patients were diagnosedas severe traumatic cerebral hernia resulted from intracranial hematoma and also those whose clinical data were retrospectively analyzed.In the emergency department,the per-operative plan was done according to the CT imaging,including the sute of burr hole on the skull,the direction and depth of carmulation,and the drainage cannula was put into the hematoma cavity for external drainage under local anesthesia.Results The successful rate of puncture was 100%.The patients's dukated oyouk contracted immediately after drainage.There are 79/ 95 patients(83.1%)had single pupil dilated and 17/31(54.8%)patients had bilateral pupils dilated.The immediately clinical effective was 76.2%.According to Glasgow outcome scale,43 of 126 patients had good recovery,26 had moderate deficits and 18 had severe sequelae,16 patients were in vegetative state,18 died. Conclusions Clinical prospective study proves that minimally invasive technique can ameliorate the cerebral hernia,prolong the operative therapie window time.

Evaluation of transcatheter arterial chemoembolization in the prevention of postoperative recurrence in 1630 patients with hepatocellular carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate postoperative transcatheter arterial chemoembolization (TACE) in the prevention of postoperative recurrence of hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>In TACE group, 987 HCC patients without any evidence of recurrence at the first TACE were treated by prophylactic TACE postoperatively within one or two months. In the control group, 643 HCC patients were not treated by prophylactic TACE for comparison. The correlation between the first recurrence and prophylactic TACE was analyzed.</p><p><b>RESULTS</b>Recurrence rate in the TACE and control group was 22.2% (219/987) and 61.6% (396/643) within 6 months (P < 0.01); 78% (770/987) and 74.7% (480/643) within 12 months (P > 0.05); 88.6% (874/987) and 80.1% (515/643) within 18 months (P < 0.01), respectively.</p><p><b>CONCLUSION</b>Postoperative prophylactic TACE may be able to suppress the recurrence formation for HCC patients with or without definite residual lesion within 6 months.</p>

Adjustment of lipiodol dose according to tumor blood supply during the transcatheter arterial chemoembolization for large hepatic carcinoma by mulitdetector helical CT / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To work out an individualized lipiodol dose in transcatheter arterial chemoembolization (TACE) for large hepatic carcinoma (HCC) according to its blood supply evaluated by CT.</p><p><b>METHODS</b>One hundred patients with HCC (diameter more than 8 cm) were studied by triphasic 5-mm-thick-section scan of multidetector helical CT. Patterns of HCC blood supply were divided into sufficient blood supply, poor blood supply, mixed blood supply and arterial-venous shunt. The dose of ultra-fluid lipiodol was determined by diameter and blood supply type of HCC. The patients were divided two groups (50 cases each), with the lipiodol perfused according to the diameter and the blood supply of tumor in one group and the iodized oil perfused according to the actual tumor diameter in the other. The filling of lipiodol in HCC was observed and conformation rate was compared in the two groups. When the diameter of HCC was less than 10 cm, 10 - 20 ml and 5 - 10 ml lipiodol was injected in to the sufficient blood supply and the poor supply groups. When the diameter of HCC was more than 10 cm, 20 - 30 ml iodized oil was injected in the sufficient blood supply group. The lipiodol dose in the mixed blood supply group was determined by the diameter of sufficient blood supply area.</p><p><b>RESULTS</b>The conformation and effective rate were 82%, 84% in the first group and 36%, 46% in the second group (P < 0.01).</p><p><b>CONCLUSION</b>A relative individualized lipiodol dose may be determined according to the blood supply pattern and the tumor diameter by CT imaging.</p>