[Molecular mechanism of geniposide in regulating GLUT2 glycosylation in pancreatic ß cells].

Type 2 diabetes mellitus( T2 DM) is a common chronic metabolic disease characterized by persistent hyperglycemia and insulin resistance. In pancreatic ß-cells,glucose-stimulated insulin secretion( GSIS) plays a pivotal role in maintaining the balance of blood glucose level. Previous studies have shown that geniposide,one of the active components of Gardenia jasminoides,could quickly regulate the absorption and metabolism of glucose,and affect glucose-stimulated insulin secretion in pancreatic ß cells,but the specific mechanism needs to be further explored. Emerging evidence indicated that glycosylation of glucose transporter( GLUT) has played a key role in sensing cell microenvironmental changes and regulating glucose homeostasis in eucaryotic cells. In this study,we studied the effects of geniposide on the key molecules of GLUT2 glycosylation in pancreatic ß cells. The results showed that geniposide could significantly up-regulate the mRNA and protein levels of Glc NAc T-Ⅳa glycosyltransferase( Gn T-Ⅳa) and galectin-9 but had no signi-ficant effect on the expression of clathrin,and geniposide could distinctively regulate the protein level of Gn T-Ⅳa in a short time( 1 h) under the conditions of low and medium glucose concentrations,but had no significant effect on the protein level of galectin-9. In addition,geniposide could also remarkably affect the protein level of glycosylated GLUT2 in a short-time treatment. The above results suggested that geniposide could quickly regulate the protein level of Gn T-Ⅳa,a key molecule of protein glycosylation in INS-1 rat pancreatic ßcells and affect the glycosylation of GLUT2. These findings suggested that the regulation of geniposide on glucose absorption,metabolism and glucose-stimulated insulin secretion might be associated with its efficacy in regulating GLUT2 glycosylation and affecting its distribution on the cell membrane and cytoplasm in pancreatic ß cells.

Prognostic significance of regional lymphadenectomy in T1b gallbladder cancer: Results from 24 hospitals in China.

BACKGROUND: Whether regional lymphadenectomy (RL) should be routinely performed in patients with T1b gallbladder cancer (GBC) remains a subject of debate. AIM: To investigate whether RL can improve the prognosis of patients with T1b GBC. METHODS: We studied a multicenter cohort of patients with T1b GBC who underwent surgery between 2008 and 2016 at 24 hospitals in 13 provinces in China. The log-rank test and Cox proportional hazards model were used to compare the overall survival (OS) of patients who underwent cholecystectomy (Ch) + RL and those who underwent Ch only. To investigate whether combined hepatectomy (Hep) improved OS in T1b patients, we studied patients who underwent Ch + RL to compare the OS of patients who underwent combined Hep and patients who did not. RESULTS: Of the 121 patients (aged 61.9 ± 10.1 years), 77 (63.6%) underwent Ch + RL, and 44 (36.4%) underwent Ch only. Seven (9.1%) patients in the Ch + RL group had lymph node metastasis. The 5-year OS rate was significantly higher in the Ch + RL group than in the Ch group (76.3% vs 56.8%, P = 0.036). Multivariate analysis showed that Ch + RL was significantly associated with improved OS (hazard ratio: 0.51; 95% confidence interval: 0.26-0.99). Among the 77 patients who underwent Ch + RL, no survival improvement was found in patients who underwent combined Hep (5-year OS rate: 79.5% for combined Hep and 76.1% for no Hep; P = 0.50). CONCLUSION: T1b GBC patients who underwent Ch + RL had a better prognosis than those who underwent Ch. Hep + Ch showed no improvement in prognosis in T1b GBC patients. Although recommended by both the National Comprehensive Cancer Network and Chinese Medical Association guidelines, RL was only performed in 63.6% of T1b GBC patients. Routine Ch + RL should be advised in T1b GBC.

Sorafenib extends the survival time of patients with multiple recurrences of hepatocellular carcinoma after liver transplantation.

AIM: to determine the efficacy and toxicities of sorafenib in the treatment of patients with multiple recurrences of hepatocellular carcinoma (HCC) after liver transplantation in a Chinese population. METHODS: twenty patients with multiple recurrences of HCC after liver transplantation were retrospectively studied. They received either transarterial chemoembolization (TACE) or TACE combined with sorafenib. RESULTS: the median survival times (MST) after multiple recurrences was 14 months (TACE+sorafenib group) and 6 months (TACE only group). The difference was significant in MST between the two groups (P=0.005). The TACE + sorafenib group had more stable disease (SD) patients than the TACE group. The most frequent adverse events of sorafenib were hand-foot skin reaction and diarrhea. In the univariate analysis, preoperative bilirubin and CHILD grade are found to be significantly associated with tumor-free survival time, the survival time after multiple recurrences and overall survival time. TACE+sorafenib group showed a better outcome than single TACE treatment group. In the multivariate COX regression modeling, the preoperative high CHILD grade was found to be a risk factor of tumor-free survival time. In addition, the preoperative high bilirubin grade was also found to be a risk factor of survival time after recurrence and overall survival time. Furthermore, survival time after recurrence and overall survival time were also associated with therapeutic schedule, which was indicated by the GROUP. CONCLUSION: Treatment with TACE and sorafenib is worthy of further study and may have more extensive application prospects.

[Effects of Radix salviae miltiorrhizae on reperfusion injury and hepatocyte apoptosis in donor liver after orthotopic liver transplantation in rats].

OBJECTIVE: To investigate the effect of Radix salviae miltiorrhizae as a cold reperfusion solution on donor liver ischemia-reperfusion injury and hepatocyte apoptosis in rat models of orthotopic liver transplantation. METHODS: Forty male SD rats were randomly divided into miltiorrhizae group, control group and sham operation group. For cold preservation of the graft, miltiorrhizae-containing Ringer's lactate solution was used as the reperfusion and preservation solution in the miltiorrhizae group, and only Ringer's lactate solution was used in the control group. All the grafts were preserved for 5 h before orthotopic transplantation. Six hours after graft reperfusion, the recipient rats were sacrificed, and the serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured, and the changes of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in the liver graft were observed. The hepatocyte apoptosis was detected using TUNEL, with the histopathological changes observed under light and electron microscopes. RESULTS: Serum ALT and AST levels were significantly lower in miltiorrhizae group than in the control group after graft reperfusion (P<0.01). Compared with the sham operation group, the apoptotic index and MDA levels in the graft was significantly decreased, while SOD and GSH-PX levels increased in miltiorrhizae group (P<0.01). Histopathological changes were obviously milder in miltiorrhizae group than in the sham operation group. CONCLUSION: Radix salviae miltiorrhizae can protect the hepatocytes from cold preservation and reperfusion-induced apoptosis and significantly alleviates ischemia-reperfusion injury in rat liver graft after orthotopic transplantation.

[Study on therapeutic mechanisms of Danshen injection in intrahepatic cholestasis of pregnancy].

OBJECTIVE: To study the therapeutic mechanisms of Danshen injection in intrahepatic cholestasis of pregnancy (ICP). METHOD: The experimental serum was collected from 6 patients with ICP before therapy when in hospital. Endothelial cells were isolated from human umbilical veins chosen among the 10 normal pregnancy according to Jaffe's method. Serum of 20% concentration of ICP and different concentration of Danshen injection were cocultured with human vascular endothelial cells (HUVECs) for 24 hours. MTT method was applied to measuring the vitality of HUVECs. The expression value of vascular endothelial growth factor (VEGF) of different groups was detected by immunocytochemistry and enzyme-linked immunosorbent assay (ELISA) respectively. RESULT: Compared with ICP group, the value of MTT and VEGF in the Danshen injection therapeutic groups were increased with the increase of concentration and moreover, 8 g x L(-1) of Danshen injection was the optical concentration. By immunocytochemistry, the expression of VEGF in HUVECs in the Danshen injection therapeutic groups was also enhanced with the increase of concentration. CONCLUSION: Danshen injection can protect HUVECs against the injury of ICP serum and promote the expression of VEGF. Danshen injection improves HUVECs by increasing the value of VEGF.