Molecular mechanism of geniposide in regulating GLUT2 glycosylation in pancreatic β cells / 中国中药杂志

Type 2 diabetes mellitus( T2 DM) is a common chronic metabolic disease characterized by persistent hyperglycemia and insulin resistance. In pancreatic β-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 β 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 β 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 βcells 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 β cells.

Demand analysis of Internet hospital service based on KANO Model / 医学研究生学报

ObjectiveAs a new mode and format of health care service, Internet hospital has created a convenient and efficient medical treatment channel for patients and promoted more access to high-quality medical resources. In order to better identify patients′ service demands of Internet hospitals and thus meet people′s diversified health needs, refined classification management of service demands of Internet hospitals is implemented by KANO model, so as to promote the improvement of service quality of Internet hospitals and enhance patient satisfaction as well.MethodsBased on the analysis ideas of KANO model, 300 patients were randomly selected from the social pharmacy of an Internet hospital for questionnaire survey and service demand survey.ResultsIn the KANO requirement attribute classification of Internet hospital service items, there were 6 items belonging to charm attribute, 10 items belonging to expectation attribute and 5 items belonging to necessity attribute. Service items corresponding to expected attributes and necessary attributes account for more than 70% of Internet hospital services.ConclusionThe application of KANO model to the service demand survey of Internet hospitals can effectively improve the service management level of Internet hospitals, and the continuous improvement of service quality of Internet hospitals requires regular monitoring of service demand changes.

Emphasis on the significance of "short hepatic portal vein" anatomy in perihepatic portal surgery / 中国实用外科杂志

Perihilar area is a clinically specific anatomical area centered on the confluence of the main portal vein with the left and right branches and bounded by the "H-shaped transverse sulcus" of the liver. Its anatomical structure is complex, involving the liver, gallbladder, regional lymph nodes and luminal systems such as portal vein, hepatic artery, bile duct and inferior vena cava. It is a difficult area in hepatobiliary surgery. Therefore, a reasonable surgical approach is of great importance. The anatomical approach strategy of "Glisson intrathecal dissociation" can clearly show the anatomical structure of various luminal systems in the perihilar area, reduce the risk of surgical error injury, and contribute to the rational individualized surgical plan decision and implementation. The short hepatic portal vein is a small branch of the main, right and left branches of the portal vein and their confluence, which distributes and travels in the transverse sulcus of the liver. The anatomical characteristics of the short hepatic portal vein should not be ignored in the implementation of "Glisson intrathecal dissociation" in the perihilar area.

Role of radical resection in patients with gallbladder carcinoma and jaundice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Gallbladder carcinoma (GBC) is a commonly-seen malignancy of the biliary tract characterized by difficult early diagnosis, rapid growth, early metastasis, and poor prognosis. Nearly half of GBC patients also have jaundice, which is a mark of the advanced stage of GBC. The role of radical resection in patients of gallbladder carcinoma with jaundice is still a matter of uncertainty, which we attempted to clarify in this study.</p><p><b>METHODS</b>Totally, 251 GBC patients who received treatment at the Eastern Hepatobiliary Surgery Hospital (EHBH) from December 2002 to January 2010 were recruited into this study. We divided them into group A (jaundice group, n=117) and group B (non-jaundice group, n=134). Clinical records and follow-up data were collected and retrospectively analyzed in both groups.</p><p><b>RESULTS</b>Compared with group A, patients in group B had a longer median survival time ((6.0±0.5) months vs. (15.0±2.6) months, P<0.01). Even in patients with stage III or stage IV GBC, the median survival time in patients without jaundice (n=111), was still longer than that in patients with jaundice (n=116) (P<0.01). The radical resection rate was lower in group A patients than in group B patients with stage III or stage IV GBC; 31.9% vs. 63.1%. However, the median survival time of patients undergoing radical resection did not show a statistical difference between jaundice patients and non-jaundice patients; (12.0±4.3) months vs. (18.0±3.0) months (P>0.05).</p><p><b>CONCLUSIONS</b>GBC with jaundice usually implies advanced stage disease and a poor prognosis for the patients. However, our findings indicate that as long as the patient's condition allows, radical resection is still feasible for GBC patients with jaundice, and may achieve a prognosis close to those GBC patients without jaundice.</p>

Hepatic blood inflow occlusion with/without hemihepatic artery control versus the Pringle maneuver in resection of hepatocellular carcinoma: a retrospective comparative analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The Pringle maneuver, which has been the standard for hepatic resection surgery for a long time, has the major flaw of ischemic damage in the liver. The aim of this research was to evaluate hepatic blood inflow occlusion with/without hemihepatic artery control vs. the Pringle maneuver in hepatocellular carcinoma (HCC) resection.</p><p><b>METHODS</b>Two hundred and eighty-one cases of resection of HCC with hepatic blood inflow occlusion (with/without hemihepatic artery control) and the Pringle maneuver from January 2006 to December 2008 in our hospital were analyzed and compared retrospectively; among them 107 were in group I (Pringle maneuver), 98 in group II (hepatic blood inflow occlusion), and 76 in group III (hepatic blood inflow occlusion without hemihepatic artery control). The operation time, intraoperative blood loss, postoperative liver function and complications were used as the endpoints for evaluation.</p><p><b>RESULTS</b>The operative duration and intraoperative blood loss of three groups showed no significant difference; alanine aminotransferase, total bilirubin and incidence of postoperative complications were significantly lower in groups II and III postoperation than those in group I.</p><p><b>CONCLUSION</b>Hepatic blood inflow occlusion without hemihepatic artery control is safe, convenient and feasible for resection of HCC, especially for cases involving underlying diseases such as cirrhosis.</p>

Establishment and characterization of a human gallbladder carcinoma cell line EH-GB1 originated from a metastatic tumor / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To establish a human gallbladder carcinoma cell line derived from a metastatic gallbladder carcinoma and identify its biological characteristics.</p><p><b>METHODS</b>Tissue samples were separated from the surgical specimen obtained from a patient with metastatic carcinoma and single-cell suspension was prepared. Then the cells were cultured in DMEM medium supplemented with 15% fetal bovine serum. The morphology of tumor cells was observed under an electron microscope. The cell growth curve was plotted. The tumorigenicity of the cell line was studied by subcutaneous inoculation in SCID mice. The cells were infected by lentiviral vector carrying fluorescent report genes (lenti-GFP and lenti-Red2) separately for expressions of GFP and Red2, respectively.</p><p><b>RESULTS</b>A novel metastatic gallbladder carcinoma cell line was successfully established and named "EH-GB1". It could be passaged for over 20 generations with typical malignant epithelial morphology and a stable growth cycle of 24 h. Tumors were formed in all of the 10 SCID mice inoculated with EH-GB1 cells subcutaneously, and the tumor cells were tumor marker CA19-9-positive. Continuous expressions of fluorescent report genes were observed in EH-GB1 cells infected by lenti-GFP and lenti-Red2.</p><p><b>CONCLUSION</b>EH-GB1 cells might be the first stable cell line of human gallbladder carcinoma established from a metastatic focus of gallbladder carcinoma. This cell line with continuous expressions of GFP and Red2 might be a novel and perfect experimental model for clinical and basic research on gallbladder carcinoma.</p>

Hepatocyte apoptosis and expression of apoptosis-regulating genes during cold preservation and reperfusion injury in rat donor liver / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the apoptosis of hepatocytes and the expression of apoptosis-regulating genes during the donor liver ischemia and reperfusion injury in rat orthotopic liver transplantation (OLT).</p><p><b>METHODS</b>Seventy-two male SD rats were randomly divided into sham operation group and transplantation group. Using Ringer's lactate solution as the perfusing and preserving solution, the grafts were preserved for 4 h before orthotopic transplantation. At 1, 6 and 24 h after the reperfusion, the recipients were sacrificed, and the serum ALT and AST levels were measured; the changes of hepatocyte apoptosis was detected by TUNEL assay, and the protein expressions of the apoptosis-regulating genes were measured by flow cytometry.</p><p><b>RESULTS</b>Serum ALT and AST levels were significantly higher in transplantation group than in the control group after reperfusion. In comparison with the control group, the rats in the transplantation group showed significantly increased apoptosis index in the livers, lowered Bcl-2 levels and increased FasL levels after the transplantation, especially at 6 h after liver reperfusion (P<0.01).</p><p><b>CONCLUSION</b>The donor liver ischemia and reperfusion injury can promote hepatocyte apoptosis, which may be related with the high expression of Bcl-2 gene and low expression of FasL after reperfusion injury in rats with orthotopic liver transplantation.</p>

Effects of Radix salviae miltiorrhizae on reperfusion injury and hepatocyte apoptosis in donor liver after orthotopic liver transplantation in rats / 南方医科大学学报

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Study on therapeutic mechanisms of Danshen injection in intrahepatic cholestasis of pregnancy / 中国中药杂志

<p><b>OBJECTIVE</b>To study the therapeutic mechanisms of Danshen injection in intrahepatic cholestasis of pregnancy (ICP).</p><p><b>METHOD</b>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.</p><p><b>RESULT</b>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.</p><p><b>CONCLUSION</b>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.</p>

Effects of subanesthetic dose of ketamine on perioperative serum cytokines in orthotopic liver transplantation / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effects of ketamine on perioperative serum cytokine levels in patients undergoing orthotopic liver transplantation (OLT).</p><p><b>METHODS</b>Twenty patients undergoing OLT were randomly divided into ketamine group (n=10) and control group (n=10). Patients in ketamine group were given intravenous bolus injection of ketamine at 0.25 mg/kg followed by ketamine infusion at 0.5 mg.kg(-1).h(-1) until the end of operation except in the anhepatic phase, whereas the control group received saline of the same amount. Arterial blood samples were obtained at the start of surgery (T(1)), 5 min before the anhepatic phase (T(2)), 5 min before recirculation (T(3)), 15 and 60 min after recirculation (T(4), T(5)), and 0, 4 and 24 h after operation (T(6), T(7), T(8)). Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and IL-10 were measured by ELISA.</p><p><b>RESULTS</b>Serum TNF-alpha, IL-6 and IL-10 levels increased significantly during anhepatic phase as compared with the baseline level (T(1)) (P<0.05), and the changes were especially obvious in IL-6 and IL-10. The levels of the cytokines kept rising after recirculation and reached the peak level at T(5)(P<0.05), followed then by rapid decline and still maintaining higher levels than the preoperative ones 24 h after operation. The levels of TNF-alpha in ketamine group between T(2) and T(7) were significantly lower than that in the control group, and the IL-6 level between T(2) and T(5) were also significantly lower in ketamine group. Serum IL-10 level did not show any significant difference between the two groups.</p><p><b>CONCLUSION</b>Ischemia and reperfusion injury of the liver and surgical stress induce pro- and anti-inflammatory cytokine responses during liver transplantation, in which event IL-6 and IL-10 are more sensitive than TNF-alpha. Ketamine can inhibit the production of TNF-alpha and IL-6 but not IL-10.</p>

Analysis of the relation between surgery and prognosis of hilar cholangiocarcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To explore the prognosis factors of hilar cholangiocarcinoma, and investigate the relation between operative procedure and prognosis of it.</p><p><b>METHODS</b>A retrospective cohort study was investigated in 198 patients with hilar cholangiocarcinoma, who were treated in our hospital from December 1997 to December 2002. There were 117 males and 81 females. The age ranged from 27 to 81 years old with a mean of 56. Jaundice (94.5%), pruritus (56.6%) and abdominal pain (33.8%) were the main present symptoms. According to Bismuth-Corlette classification, there were 14 type I cases, 19 type II cases, 12 type IIIa cases, 15 type IIIb cases, 112 type IV cases and 26 unclassifiable cases. One hundred and forty four cases received open operative treatment, and the others only were treated with endoscopic approach (including ERBD or EMBE 21 cases, ENBD 31 cases) or percutaneous transhepatic cholangiodrainage (2 cases). Tumor resection was performed on 120 cases with a resection rate of 83.3%, included radical resection 59 cases (41.0%). Twenty-four cases underwent paunched biliary exploration and drainage.</p><p><b>RESULTS</b>The Cox's regression model analysis showed that occupation, preoperative maximum total serum bilirubin level, operative procedure and postoperative adjuvant radiation affected postoperative survival significantly, but gender, age, choledocholithiasis, hepatitis, preoperative serum CA19-9 level, Bismuth-Corlette type, histopathologic grading and postoperative chemotherapy were not significant prognostic factors. The postoperative survival of biliary drainage group, palliative resection group and radical resection group, which statistically differed pairwise. Between ERBD or EMBE group and palliative resection group, there was no statistical difference. So was between ERBD or EMBE group and biliary drainage group, or between ENBD group and biliary drainage group. The survival differed statistically between ERBD or EMBE group and ENBD group.</p><p><b>CONCLUSIONS</b>Operative procedure was the most important prognosic factor of hilar cholangiocarcinoma, radical resection still was the primary measure to cure and long term survival. For irresectable hilar cholangiocarcinoma, the effect of ERBD or EMBE could not be considered to be worse than that of open operative treatment.</p>

Partial hepatectomy with skeletonization of the hepatoduodenal ligament for hilar cholangiocarcinoma / 中华外科杂志

<p><b>OBJECTIVE</b>To sum up author's experience and to define the role of partial hepatectomy with skeletonization resection in the treatment of hilar cholangiocarcinoma.</p><p><b>METHODS</b>Between January 1999 and December 2001, 67 patients underwent exploration in our hospital. The clinical records of these patients were reviewed.</p><p><b>RESULTS</b>Sixty-five (97%) patients underwent surgical resection. Forty-nine patients (73%) had curative resection [22 skeletonization resection (SR), and the other 27 undergone SR combined with partial hepatectomy]. According to the Bismuth-Corlett classification, tumors were classified into four types. SR was performed in type I (5 cases) and type II (17 cases). Right lobectomy with right caudate lobectomy was performed in type IIIa (6 cases), left lobectomy with left caudate lobectomy in type IIIb (15 cases). Right lobectomy with whole caudate lobectomy (3 cases), left lobectomy with whole caudate lobectomy (9 cases), and quadrate lobectomy (2 cases) were undertaken in type IV. We successfully did SR and left lobectomy with whole caudate lobectomy in 2 patients (3%) who had suffered palliative biliary cancer resection and cholangiojejunostomy before. Eight patients (12%) had local resection of the tumor with Roux-en-Y hepaticojejunostomy reconstruction and intrahepatic bile ducts support. Two patients (3%) had palliative biliary drainage. Combined portal vein resection was performed in 13 (20%) patients and hepatic artery resection in 27 (40.3%). Twenty-four (35.8%) patients had no postoperative complications, and 20 (30.2%) patients developed major complications. Of the 20 patients with major complications 14 recovered; the remaining 6 patients died of liver-renal failure with other organ failure or of heart attack, intraabdominal bleeding, and gastrointestinal bleeding in 7, 12, 14, 42, 57, or 89 days after surgery. Thirty days operative mortality was 4.5%. The median survival of patients with curative resection was 16 months (ranging from 1 to 41 months), while the median survival with palliative operation was 7 months (ranging from 1 to 16 months).</p><p><b>CONCLUSIONS</b>Partial hepatectomy with skeletonization resection for hilar cholangiocarcinoma can be performed with acceptable morbidity and mortality. For curative treatment of hilar cholangiocarcinoma, Caudate lobectomy is always recommended in Bismuth type III/IV.</p>

Prognostic analysis of patients suffering from distal bile duct cancer / 中华外科杂志

<p><b>OBJECTIVE</b>To study prognostic factors after surgical procedure for distal bile duct cancer.</p><p><b>METHODS</b>A retrospective clinical analysis was made in 173 cases of distal bile duct cancer, admitted to our hospital from February 1996 to December 2002. Fourteen clinicopathologic factors that could possibly influence survival were selected. A multivariate analysis of these individuals was performed using the Cox Proportional Hazards Model.</p><p><b>RESULTS</b>There were 99 males and 74 females. The age ranged from 27 to 74 years old with a mean of 55.5. Radical resection was performed on 152 cases with radical resection rate of 87.9%. 29 cases died of liver metastasis with a rate of 46.8% in total death cases. The statistical analysis showed that surgical procedure, lymph node metastasis and pathological differentiation grade affected postoperative survival significantly, but transfusion, invasion of pancreas, postoperative radiotherapy and chemotherapy, ERCP, diameter of tumour, serum level of CA-19-9, preoperative total serum bilirubin level (TBIL), ratio of albumin to globulin (A/G), sex and age are not significant factors influencing postoperative survival.</p><p><b>CONCLUSIONS</b>Radical resection is only curative treatment modality. Aggressive treatment and prevention on postoperative liver metastasis is a important strategy to improve the survival for distal bile duct cancer.</p>

Surgical treatment of hepatocellular carcinoma with tumor thrombus in the inferior vena cava / 中华外科杂志

<p><b>OBJECTIVE</b>To clarify the proper surgical procedure of treating hepatocellular carcinoma (HCC) with a tumor thrombus in the inferior vena cava (IVC).</p><p><b>METHODS</b>Four patients with HCC with a tumor thrombus in the IVC underwent hepatectomy and thrombectomy. Following hepatectomy, tumor thrombus was removed by incising the wall of the IVC in 3 patients and from the hepatic vein in one patient. The 3 patients underwent thrombectomy under either hepatic vascular exclusion (HVE) or Satinsky's vascular clamping.</p><p><b>RESULTS</b>All the operations were successful without operative death and major complications. The postoperative course was uneventful in 3 patients and pleural effusion occurred in one patient who needed thoracentesis. Follow-up showed 3 patients died after 30, 10 and 14 months, respectively, and one patient is alive for 7 months.</p><p><b>CONCLUSIONS</b>HCC with tumor thrombus in the IVC is operable and the proper procedure is hepatectomy plus thrombectomy.</p>