A comparison of current guidelines for the management of intrahepatic cholangiocarcinoma worldwide / 中华外科杂志

Intrahepatic cholangiocarcinoma (ICC) is the second most common human liver malignancy and its incidence rate has been gradually increasing worldwide over the past decades. Surgical resection (R0 resection) is the preferred potentially curative treatment for ICC patients. However, due to its conceal clinical features and high invasiveness, most patients have lost the opportunity for surgical resection at the time of diagnosis. In recent years, with the rapid development of targeted therapy and immunotherapy, which is represented by immune checkpoint inhibitors, clinicians are expected to provide more effective treatment options for patients with mid-stage or advanced ICC. At present, there are still controversial opinions on different guidelines regarding preoperative biliary drainage, the extent of hepatectomy, the definition of R0 resection, the width of the resection margin, lymph node dissection, postoperative recurrence, adjuvant therapy, etc. In this review, 12 guidelines or expert consensus published worldwide from 2012 to 2022 (including 4 Chinese guidelines, 4 European guidelines, 2 American guidelines and 2 Japanese guidelines) were retrieved. Focusing on sorting and comparing the current views on clinical management of ICC in different guidelines, this review aims to provide reference information for ICC clinical management and decision-making.

Sal B attenuates rat hepatocytes injury induced by hypoxia/reoxygenation via modulation of SIRT1/NF-κB/p53 pathway / 中国药理学通报

Aim To investigate the effect of salvianolic acid B(Sal B) on the attenuation of rat hepatocyte in-jury induced by hypoxia/reoxygenation(H/R) and its possible molecular mechanism. Methods Rat hepato-cytes BRL-3A were cultured in vitro. H/R injury mod-el was established and then BRL-3A cells were pretrea-ted with Sal B. The viability of cells was measured by CCK-8 assay;the expression of ALT and AST was de-tected by microplate assay; the levels of TNF-α and IL-1β were determined by ELISA; the apoptosis was detected by flow cytometry;the protein and mRNA lev-els of SIRT1, NF-κB p65, p53, Bax and Bcl-2 were measured by Western blot and qPCR. Results H/R intervention decreased the viability and increased the apoptosis of cells;the production of ALT, AST, TNF-α and IL-1β was elevated;the protein and mRNA lev-els of SIRT1, Bcl-2 were reduced, but the levels of NF-κB p65, p53 and Bax increased. After pretreated with Sal B, the viability of cells increased while the apoptosis decreased; the expression of ALT, AST, TNF-α and IL-1β was inhibited;moreover,the protein and mRNA levels of SIRT1,Bcl-2 were enhanced,and the levels of NF-κB p65, p53 and Bax decreased sig-nificantly. Conclusion Sal B may attenuate rat hepa-tocyte injury induced by H/R via the SIRT1/NF-κB/p53 pathway.

Effects of co-expression plasmid of human tPA and VEGF165 on the proliferation of vascular cells and fibrinolysis activity / 中南大学学报(医学版)

OBJECTIVE@#To observe the expression of the co-expression plasmid of tissue-plasminogen activator (tPA) and vascular endothelia growth factor165 (VEGF165) in vascular smooth muscle cells (VSMC) and to study the effect of expressing products on the proliferation of VEC and VSMC and fibrinolysis activity.@*METHODS@#The co-expression plasmid of tPA and VEGF165 (pBudCE4.1/tPA-VEGF165) was transfected into VSMC with the lipofection. The expression of tPA and VEGF165 at mRNA level was detected by RT-PCR and the protein level expression was detected by enzyme linked immunosorbent assay (ELISA). The fibrinolysis activity of culture medium of VSMC transfected tPA and VEGF165 genes was detected by fibrin plate technique. The VEC and VSMC were cultured with culture medium of VSMC transfected tPA and VEGF165 genes. And the proliferation of VEC and VSMC was evaluated with monoterazolium (MTT) and flow cytometry (FCM).@*RESULTS@#The expression of tPA and VEGF165 at mRNA and protein levels in the transfected VSMC was demonstrated by RT-PCR and ELISA, respectively. The VSMC culture medium of transfected genes possessed evidently fibrinolysis activity. The expression products of tPA and VEGF165 in the VSMC had an evident effect on the VEC proliferation. But it had not an effect on the VSMC proliferation.@*CONCLUSION@#The eukaryotic co-expression plasmid of tPA and VEGF165 can be expressed in transfected VSMCs. The expression products have an obvious biological activity. The present study lay the foundation for future making use of tPA and VEGF165 to prevent and treat vascular stenosis in transplanted heart.

Effects of platelet derived growth factor antisense oligodeoxynucleotides and tissue-type plasminogen activator gene transfection on inhibition of intimal proliferation / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To observe the effects of co-transfection of platelet derived growth factor antisense oligodeoxynucleotides (PDGF-AODN) and tissue-type plasminogen activator (tPA) gene on inhibition of intimal proliferation of auto-transplantion artery.</p><p><b>METHODS</b>One hundred male New Zealand rabbits were randomly divided into four groups (25 in each): Group A (control group), Group B (PDGF-AODN transfection group), Group C (tPA gene transfection group) and Group D (PDGF-AODN and tPA co-transfection group). The left and right external iliac arteries were transplanted reciprocally. The transplanted arteries were respectively soaked in PDGF-AODN, pBudCE4.1/tPA and PDGF-AODN plus pBudCE4.1/tPA solution about 15 minute before transplantation. The rabbits were sacrificed at 3d, 1w, 2w, 4w and 8w after operation. The specimens were harvested for pathologic examination, electron microscopy, chromogenic substrate test, 3H-TdR incorporation test and immunohistochemical staining.</p><p><b>RESULT</b>The scan electron microscopy showed that there were a few thrombocytes on vas-wall of Group C and D without thrombus, whereas there were abundant thrombocytes and thrombus forming on vas-wall of Group A and B. The intimal area, stenosis ratio of transplanted artery, 3H-TdR incorporation,the number of PDGF positive cell in Group D were significantly less than those in Group A (P<0.01),Group B and Group C (both P<0.05). The activity of tPA gene products in transplanted vas-wall of Group D was significantly higher than that of Group A (P<0.01).</p><p><b>CONCLUSION</b>Local co-transfection of PDGF-AODN and tPA gene can effectively inhibit the proliferation of vascular smooth muscle cells, hyperplasia of intima and restenosis of transplanted artery.</p>

Protective effect of ecdysterone on PC12 cells cytotoxicity induced by beta-amyloid25-35 / 中国结合医学杂志

<p><b>OBJECTIVE</b>To examine the protective effect of ecdysterone (ECR) against beta-amyloid peptide fragment(25-35) (Abeta(25-35))-induced PC12 cells cytotoxicity, and to further explore its mechanism.</p><p><b>METHODS</b>Experimental PC12 cells were divided into the Abeta group (treated by Abeta(25-35) 100 micromol/L), the blank group (untreated), the positive control group (treated by Vit E 100 micromol/L after induction) and the ECR treated groups (treated by ECR with different concentrations of 1, 50 and 100 micromol/L). The damaged and survival condition of PC12 cells in various groups was monitored by lactate dehydrogenase (LDH) release and MTT assay. The content of malondialdehyde (MDA) was measured by fluorometric assay to indicate the lipid peroxidation. And the antioxidant enzymes activities in PC12 cells, including superoxide dismutases (SOD), catalase (CAT) and glutathione peroxidase (GSH-Px), were detected respectively.</p><p><b>RESULTS</b>After PC12 cells were treated with Abeta(25-35) (100 micromol/L) for 24 hrs, they revealed a great decrease in MTT absorbance and activity of antioxidant enzymes, including SOD, CAT and GSH-Px as well as a significant increase of LDH activity and MDA content in PC12 cells (P < 0.01). When the cells was pretreated with 1-100 micromol/L ECR for 24 hrs before Abeta(25-35) treatment, the above-mentioned cytotoxic effect of Abeta(25-35) could be significantly attenuated dose-dependently, for ECR 50 micromol/L, P < 0.05 and for ECR 100 micromol/L, P < 0.01. Moreover, ECR also showed significant inhibition on the Abeta(25-35) induced decrease of SOD and GSH-Px activity, but not on that of CAT.</p><p><b>CONCLUSION</b>ECR could protect PC12 cells from cytotoxicity of Abeta(25-35), and the protective mechanism might be related to the increase of SOD and GSH-Px activities and the decrease of MDA resulting from the ECR-pretreatment.</p>

To study the effects of local co-transfection vascular endothelial growth factor165 and tissue-type plasminogen activator genes on inhibiting intimal hyperplasia after operation injury artery in rabbits / 中华外科杂志

<p><b>OBJECTIVE</b>To observe the effects of local co-transfection vascular endothelial growth factor165 (VEGF165) and tissue-type plasminogen activator genes on inhibiting intimal hyperplasia and restenosis in rabbits artery after operation injury and possible mechanisms.</p><p><b>METHODS</b>Micrology operation injury was used to establish the model of intimal injury of right external iliac artery in rabbits. To select 120 male New Zealand rabbits and were randomly divided into 3 groups (n = 40, in each group): Group A (physiological brine control group), Group B (pBudCE4.1 group), Group C (pBudCE4.1/VEGF165-tPA group). The vas-wall of micrology operation injury were infused respectively physiological brine, pBudCE4.1 and pBudCE4.1/VEGF165-tPA transfection solution by micro-injector. Each group were divided into 5 subgroups (n = 8, in each subgroup) randomly according to the sacrifice times (2 d, 1 week, 2 week, 4 week and 8 week after operation). The injured vascular specimen were harvested for pathology test, electric microscopy study, reverse transcription-PCR examining and immunochemistry detecting.</p><p><b>RESULTS</b>The intimal area and narrow ratio of vases in Group C at every time point after operation were significantly lessened than that in Group A and Group B (P < 0.01). The narrow ratio of vases in Group C at 8 week after operation were decreased respectively by 57.9% and 59.0% than that in Group A and B. The expression of VEGF165 mRNA in Group C were increased significantly than that in Group A and B at every time point after operation (P < 0.01), the expression reached the peak at 1 week and continued to 4 week after operation. Immunohistochemical identified that tPA positive cell in Group C were significantly increased than that in Group A and B (P < 0.01) at every time point after operation.</p><p><b>CONCLUSION</b>Local co-transfection VEGF165 and tPA genes could restrain intimal hyperplasia and restenosis of vas, which lay a foundation for future multi-gene therapy of vascular intimal hyperplasia.</p>

The study on platelet-derived growth factor and proliferating cell nuclear antigen antisense oligodeoxynucleotides together inhibiting the stenosis of transplanted vascular / 中华外科杂志

<p><b>OBJECTIVE</b>To study the effect of platelet-derived growth factor (PDGF) and proliferating cell nuclear antigen (PCNA) antisense oligodeoxynucleotides (AODN) together on inhibiting the proliferation of the stenosis of transplanted vascular.</p><p><b>METHODS</b>The left and right external iliac arteries (length 1.0 cm) of rabbits were transplanted reciprocally. The transplanted vascular were respectively soaked in liposomes, PDGF-AODN, PCNA-AODN and PDGF-AODN adding PCNA-AODN solution about 20 minute, the vascular anastomotic were sutured by 8/0 suture of soaked in AODN solution. Four weeks later, the specimens were harvested for microscopy. The pathological morphology of transplanted vascular were observed under microscope (HE). The intimal thickness and area, stenosis ratio(%) of transplanted vascular were calculate and analysed statistically among group by computer system. The number of positive cells of PDGF's mRNA in transplanted vascular wall were counted with in situ hybridization histo-cytochemistry and the number of positive cells of PCNA's protein in transplanted vascular wall were counted by S-P immunochemistry.</p><p><b>RESULTS</b>The intimal thickness and area, stenosis ratio of transplanted vascular, the number of PDGF and PCNA positive cell in PDGF-AODN adding PCNA-AODN group were significantly lower than those in other group (P < 0.01), and that were lower evidently than PDGF-AODN group and PCNA-AODN group.</p><p><b>CONCLUSION</b>PDGF and PCNA antisense oligodeoxynucleotides together could significantly inhibit the proliferation of vascular smooth muscle cell and stenosis of transplanted vascular.</p>