End-to-end bile duct anastomosis and percutaneous transhepatic cholangial drainage for iatrogenic bile duct injuries / 中华肝胆外科杂志

Objective:A novel bile duct end-to-end anastomosis and percutaneous transhepatic cholangial drainage (PTCD) were designed to treat iatrogenic bile duct injuries, and the clinical efficacy and technical advantage of this combined treatment were analyzed.Methods:Clinical data from 11 patients with iatrogenic bile duct injuries treated between February 2012 to July 2021 was retrospectively analyzed. There were 4 females and 7 males, with age of (47.5±15.3) years old. The types of bile duct injuries were: Bismuth type 1 ( n=7), Bismuth type Ⅱ ( n=1), Bismuth type Ⅲ type ( n=1), combined Bismuth type 1 and type 2 ( n=1), and Bismuth type Ⅳ ( n=1). Repair operations were performed at the time of the initial surgical procedures in 8 patients. The remaining 3 patients had their repair done 2 days, 9 days and 5 months, respectively, after the initial operations. All patients underwent successful bile duct end-to-end anastomosis and PTCD without use of T-tubes. Results:All biliary injuries were successfully repaired with no operative mortalities. Two patients who underwent end-to-end anastomosis of common hepatic duct developed anastomotic bile leakage. The amount of bile leakage was small and bile leakage resolved with conservative treatment in 1 patients 3 days after surgery, and was treated successfully by percutaneous peritoneal drainage for 2 weeks in the other patient. There were no other complications, including stricture formation or cholangitis which developed in other patients. All patients’ liver functions recovered well. The percutaneous biliary drainage tube was removed 6 months after operation in 1 patient. The remaining patients had their drainage tubes removed 3 months after operation. On follow-up, all patients had no history suggestive of cholangitis, jaundice and other symptoms. The liver functions were normal on laboratory examinations. No stricture or dilatation of intrahepatic bile ducts were detected on imaging examinations. The cure rate was 100% (11/11).Conclusion:Surgical repair of biliary tract injuries should aim to preserve sphincter of Oddi function and maintain normal physiological pathway of bile excretion. PTCD helped smooth recovery of an end-to-end anastomosis, lowered severity of physical disability of patients and minimized occurrence of medical disputes.

Downregulation of GNAI3 Promotes the Pathogenesis of Methionine/Choline-Deficient Diet-Induced Nonalcoholic Fatty Liver Disease

Background/Aims@#The pathogenesis of nonalcoholic fatty liver disease (NAFLD) has not be fully elucidated, and the lack of therapeutic strategies for NAFLD is an urgent health problem. Guanine nucleotide binding protein, alpha inhibiting activity polypeptide 3 (GNAI3) participates in several biological processes, but its relationship with lipid metabolism and NAFLD has not yet been reported. We aimed to determine the function of GNAI3 in the development of NAFLD. @*Methods@#Mice were fed a methionine and choline-deficient diet to induce NAFLD. An NAFLD model in HepG2 cells was induced by free fatty acid treatment. GNAI3 levels in HepG2 cells were downregulated by shRNA. Protein levels of related proteins were evaluated by Western blotting, and mRNA levels were determined by quantitative reverse transcription polymerase chain reaction. Hematoxylin and eosin and Oil Red O staining were used to observe histological changes in liver tissue. @*Results@#The dysregulated hepatic lipid metabolism in the NAFLD mouse model was enhanced by GNAI3 knockout, which also provoked worse liver damage. In the NAFLD model in HepG2 cells, the downregulation of GNAI3 promoted cellular lipid accumulation and enhanced the changes in lipid metabolic enzyme levels. @*Conclusions@#This study demonstrates that GNAI3 participates in the development of NAFLD in both cellular and mouse models. The data indicate that GNAI3 is a potential new target for the treatment of NAFLD in humans.

FOLFIRINOX as a first line therapy in locally advanced pancreatic cancer and borderline resectable pancreatic cancer: a Meta-analysis / 中华肝胆外科杂志

Objective To evaluate the efficacyof the first line chemotherapy FOLFIRINOX (5-Fu,Leucovorin calcium,Irinotecan,Oxaliplatin) as the treatment of pancreatic cancer.Methods Pertinent studies were identified from the PubMed,Cochrane Library and EMBASE.The outcomes were resection rate and radical (R0) resection rate were analyzed.Data were expressed as weighted pooled proportions with 95％ confidence intervals (95％ CI).Results There were thirteen studies with 408 patients with LAPC and BRPC included.After the treatment,42.0％ (95％ CI:28.0％ ～56.0％) tumorswere resected and 41.0％ (95％ CI:37.0％ ～45.0％) were underwentR0 resection,and median overall survival ranged from 15.5 to 34.5 months,median progression-free survival ranged from 10.0 to 17.8 months.Conclusion The meta-analysis shows that down-staging after first line FOLFIRINOX-based therapy is noticeable in patients with borderline resectable/unresectable PC,and the adverse events were in control.

Diagnosis and treatment of thrombosis of right hepatic artery after surgery for severe pancreatitis / 中华消化外科杂志

The treatment for severe pancreatitis includes surgical and non-surgical methods,and the key points of treatment include surgical timing,surgical method selection and the management of postoperative complications.Hepatic artery thrombosis after surgery for severe pancreatitis is rarely seen,and few experiences in the diagnosis and treatment for this disease have been summarized.A patient with the course of severe pancreatitis of 10 years and suffered from 3 different kinds of diseases including thrombosis of right hepatic artery was cured by open surgery for 2 times and intervention therapy in the Affiliated Hospital of Hainan Medical College in October 2011.The treatment experience was summarized based on the clinical data of this patient.

Treatment of primary hepatic neuroendocrine tumors / 中华普通外科杂志

Objective To explore the treatment of primary hepatic neuroendocrine tumors (PHNET).Methods The therapeutic treatments of 9 PHNET patients from January 2003 to January 2010 in 3 hospitals were retrospective analyzed and followed up.Results Diagnosis of PHNET was confirmed immunohistochemically and by excluding extrahepatic primary sites.The survival is significantly dependent on tumor resectability.One patient received only radiotherapy and one with only chemotherapy,one with radiofrequency ablation.Six patients received R0 resection,one received postoperative radiotherapy,one with TACE perioperatively and internal radiotherapy.Two patients were lost to follow up 3 patients died and 4 were alive.Intrahepatic recurrence was found in 1 patient and metastasis to bone in 2 patients.Survival time ranged from 11 days to 66 months.Conclusions PHNET is an extremely rare entity with difficulty in early diagnosis.Curative liver resection integrated with transarterial chemoembolization or radiotherapy is considered to be an effective modality.

Anatomical multiple hepatic segmentectomy by selective occlusion of hepatic inflow for the treatment of primary hepatic cancer / 中华消化外科杂志

Anatomic hepatic resection not only enables enough tumor-free resection margin,but also guarantee the maximal remnant of normal liver tissue.A 61-year-old male patient with hepatic cancer was admitted to the Affiliated Hospital of Hainan Medical College in February 2012.Multiple space-occupying lesions were found in segment Ⅵ,Ⅶ and Ⅷ by computed tomography (CT).The results of CT volumetry analysis showed that the left hemihepatic volume was lesser than the minimal limit of survival,so anatomic hepatic segmentectomy of Ⅵ,Ⅶ and Ⅷ with preservation of segment Ⅴ was designed to guarantee the maximal remaining of normal liver tissue.Glisson's pedicle transection was used twice to divide the right hemihepatic Glisson's pedicle,segment Ⅵ and Ⅶ Glisson's pedicle,respectivley,then the resection line was determined,and anatomical hepatic segmentectomy of Ⅵ,Ⅶ and Ⅷ was completed.With the procedures adopted,the hepatic ischemia reperfusion injury and hemodynamic instability were maximally reduced during operation.

Inhibitory effect of EGCG on proliferation and HIF-1α/VEGF expression in cell line HepG2 / 中国病理生理杂志

AIM: To study the molecular mechanism of EGCG on inhibiting the growth of hepatic carcinoma. METHODS: The proliferation of hepatic cell line HepG2 cultured with different doses of EGCG was studied by MTT and suspension/adherence methods. The effect of EGCG on the expression of HIF-1α/VEGF at mRNA and protein levels in vitro and in vivo was evaluated by RT-PCR and Western blotting, respectively. The inhibition of EGCG on the growth of tumor implanted into athymic nude mice was also observed. RESULTS: The proliferation of hepatic cell line HepG2 was inhibited by EGCG in a dose-dependent manner. The expression of HIF-1α/VEGF was suppressed markedly by EGCG at protein level. However, the inhibitory effect of EGCG on the mRNA expression was only observed on VEGF, not on HIF-1α. In the animal experiment, the implanted tumor growth was inhibited by 39.8%±5.1%. CONCLUSION: EGCG suppresses the hepatic carcinoma cell growth, and interrupts the HIF-1α/VEGF signaling pathway significantly, indicating a fundamental mechanism of EGCG for inhibiting tumor growth.

Intrathymic inoculation of liver specific antigen alleviates liver transplant rejection / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To study the effects of liver specific antigen (LSA) on liver allotransplantation rejection.</p><p><b>METHODS</b>Orthotopic liver transplantation was performed in this study. Group I: syngeneic control (Wistar-to-Wistar); Group II: acute rejection (SD-to-Wistar). Group III: thymic inoculation of SD rat LSA day 7 before transplantation. The observation of general condition and survival time, rejection grades and the NF-kappaB activity of splenocytes were used to analyze severity of acute rejection and immune state of animals in different groups.</p><p><b>RESULTS</b>The general condition of group I was fair post transplantation with no sign of rejection. All recipients of group II died within days 9 to 13 post transplantation with median survival time of 10.7 +/- 1.37 days. As for group III, 5 out of 6 recipients survived for a long period with remarkably better general condition than that of group II. Its rejection grades were significantly lower than group II (P<0.05). NF-kappaB activity was only detected in group I between days 5 and 7 after transplantation, whereas high activity of NF-kappaB was detected at all points in group II and low NF-kappaB activity was detected in group III which was significantly lower than that of group II (P<0.05).</p><p><b>CONCLUSIONS</b>LSA is an important transplantation antigen directly involved in the immunorejection of liver transplantation. Intrathymic inoculation of LSA can alleviate the rejection of liver allotransplantation, grafts survive for a period of time thereby, allowing a novel way to liver transplantation immunotolerance.</p>

4-1BB gene expression in peripheral blood mononuclear cells from orthotopic liver transplant recipients with graft acceptance / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the gene expression of 4-1BB in peripheral blood mononuclear cells (PBMCs) and the possible significance of the 4-1BB pathway after clinical orthotopic liver transplantation (OLT).</p><p><b>METHODS</b>4-1BB mRNA levels in PBMCs from 22 OLT patients were analyzed by RT-PCR. 4-1BB protein expressed on the surface of CD(4)(+) and CD(8)(+) T cells were detected by flow cytometry, and visualized with direct immunofluorescence and confocal fluorescence microscopy. Patients with primary liver cancer (PLC) and healthy volunteers served as controls. Six cases of recently performed liver transplantation were also observed in this study.</p><p><b>RESULTS</b>4-1BB mRNA was detected in PBMCs from both liver transplant patients with long-term graft acceptance (22 cases) and from transplant patients on day 1 to day 3 post-transplantation (6 cases), but was not found in PBMCs from transplant patients on day 7 to day 30 post-transplantation (6 cases). 4-1BB mRNA was also not found in samples from 8 of the healthy controls and 7 of the PLC patients, though very low expression was detected in the other 4 healthy volunteers and 6 PLC patients. Simultaneously, 4-1BB protein was expressed at nearly undetectable levels on CD(4)(+) and CD(8)(+) T cells from healthy controls, PLC patients, as well as OLT patients within the first month post-transplantation (6 cases). However, 4-1BB expression was found on the surface of CD(4)(+) and CD(8)(+) T cells from liver transplant patients with long-term graft acceptance. Direct immunofluorescent staining and confocal fluorescence microscopy clearly revealed evidence of 4-1BB protein on cell membranes of CD(4)(+) and CD(8)(+) T cells from liver transplant patients with long-term graft acceptance. Simultaneously, a significantly higher percentage of CD(3)(+) CD(25)(+) T cells were found in liver transplant patients with long-term graft acceptance group as compared with the healthy control group (P < 0.05). The expression of 4-1BB protein on T cells did not correlate with the survival time of OLT patients postoperation.</p><p><b>CONCLUSIONS</b>This study demonstrates that although patients remain in stable condition after liver transplantation under the treatment of immunosuppressants, activated T cells are present to some extent and 4-1BB protein may be involved in this process. Effector T-cells can exert permanent immunoresponses against grafts under these circumstances. Therefore, we conclude that a new immune response balance is established under the combination of both treatment with immunosuppressants and natural immune responses against alloantigens. Manipulation of the 4-1BB/4-1BBL pathway may provide a therapeutic technique for prolonging graft survival.</p>

Inhibitory effect of tea polyphenols on renal cell apoptosis in rat test subjects suffering from cyclosporine-induced chronic nephrotoxicity / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the inhibitory effect of tea polyphenols on renal cell apoptosis in rat test subjects suffering from cyclosporine A (CsA)-induced chronic nephrotoxicity.</p><p><b>METHODS</b>Four groups of rats with CsA-induced chronic nephrotoxicity were respectively treated with vehicle olive oil, tea polyphenols, CsA and tea polyphenols plus CsA. At the end of the 28th day of treatment, 24 hours urine and blood samples were obtained, and the animals were then sacrificed. The serum and urine samples were analysed for creatinine clearance, and kidney tissue was used for pathologic analysis of renal tubular injury and interstitial fibrosis. The TUNEL assay, apoptosis-related enzyme caspase-3 mRNA detected by RT-PCR, and its enzymatic activity were analysed for the possible detections of cell apoptosis.</p><p><b>RESULTS</b>CsA-treated rats displayed increased apoptosis of the tubular and interstitial cells, in comparison with vehicle-treated controls (18.3 +/- 4.6 vs 4.8 +/- 1.3 cells/mm(2), P < 0.05). In comparison with animals treated by CsA, animals treated with CsA plus tea polyphenols demonstrated significantly improved levels of creatinine clearance (0.12 +/- 0.03 vs 0.22 +/- 0.02 ml.min(-1).100 g(-1) body weight, P < 0.05), tubular injury (2.29 +/- 0.43 vs 1.42 +/- 0.26, P < 0.05), and interstitial fibrosis (2.83 +/- 0.20 vs 1.46 +/- 0.19, P < 0.05), and showed a statistically significant decrease in tubular and interstitial cell apoptosis (18.3 +/- 4.6 vs 7.7 +/- 2.1 cells/mm(2), P < 0.05). The expression of caspase-3 mRNA and caspase-3 activity was significantly higher in the CsA-treated group than that of the CsA plus tea polyphenols (TP)-treated group (P < 0.05).</p><p><b>CONCLUSION</b>These results suggested that tea polyphenols significantly inhibits apoptosis of the tubular and interstitial cells in rats with cyclosporine-induced chronic nephrotoxicity, and that tea polyphenols may be useful to prevent CsA-associated kidney toxicity.</p>

CsA downregulates IFN-gamma gene transcription after liver transplantation by inhibiting NF-kappa B activity / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the relationship between NF-kappa B activity and IFN-gamma gene expression, as well as the histopathological changes following liver transplants, both with and without cyclosporin A (CsA) treatment.</p><p><b>METHODS</b>Sixty male Wistar and Thirty male SD rats were subjected to orthotopic liver transplants. Fourty-five of the Wistar rats were used as recipients, and were divided into 3 groups: group I, syngeneic control (Wistar-to-Wistar); group II, acute rejection (SD-to-Wistar); and group III: acute rejection treated with cyclosporin A by intramuscular injection (SD-to-Wistar + CSA). After the liver transplants, electrophoretic gel mobility shift assay was used to analyze NF-kappa B activity in the splenocytes of recipient rats, and RT-PCR was used to measure IFN-gamma gene expression in grafted liver specimens. In addition, histopathological examinations were performed to assess the severity of acute liver rejection.</p><p><b>RESULTS</b>In group I, low levels of NF-kappa B activity were only detectable on day 5 and 7 post-transplant, and only weak IFN-gamma mRNA expression was observed at all time points. By contrast, both high NF-kappa B activity and high expression levels of IFN-gamma mRNA were detected at all time points in group II. In group III, NF-kappa B activity and IFN-gamma mRNA expression were significantly inhibited, as compared to group II (P < 0.05). A good correlation was found between NF-kappa B activity and IFN-gamma mRNA expression (r = 0.815). In addition, NF-kappa B activity and IFN-gamma mRNA expression mirrored histopathological changes in all three experimental groups.</p><p><b>CONCLUSIONS</b>Changes in IFN-gamma mRNA expression levels after liver transplantation are at least partially due to changes in levels of NF-kappa B activity. CsA appears to downregulate NF-kappa B activity, thus inhibiting IFN-gamma gene transcription. Blocking the NF-kappa B mediated transcription pathway may be of benefit in preventing liver transplant rejection.</p>

The effect of an antioxidant tea polyphenols on cell apoptosis in rat model of cyclosporine-induced chronic nephrotoxicity / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effect of tea polyphenols on cell apoptosis in rat model of cyclosporine-induced chronic nephrotoxicity.</p><p><b>METHODS</b>Four groups of animals in rat model of cyclosporine-induced chronic nephrotoxicity were respectively treated by olive oil (n = 6), tea polyphenols (TP, n = 6), cyclosporine A (CsA, n = 8) and TP plus CsA (n = 8). At the end of 28th day of treatment, all animals were sacrificed and blood was analyzed for blood serum creatinine and creatinine clearance, kidney tissue for pathologic analysis. The TUNEL assay, caspase-3 mRNA expression detected by reverse transcription-polymerase chain reaction (RT-PCR) and caspase-3 activity were used for the analysis of cell apoptosis.</p><p><b>RESULTS</b>CsA plus TP ameliorated the CsA-induced decrease of renal function and interstitial fibrosis. There was a significant increase in the number of apoptosis-positive cells in the CsA-vs-CsA plus TP-treated group at four weeks (18.9 +/- 3.3 vs. 7.7 +/- 1.4, P < 0.05). The expression of caspase-3 mRNA and caspase-3 activity of CsA-treated group was significantly higher than that of CsA plus TP-treated group (P < 0.05).</p><p><b>CONCLUSION</b>These results indicate that antioxidant tea polyphenols significantly inhibit apoptosis of tubular and interstitial cells in rat model of chronic cyclosporine-induced nephrotoxicity, and suggest that the decrease of cell apoptosis exerted by tea polyphenols may be one of mechanisms to protect renal function and tissue structure.</p>

Role of adenovirus mediated CTLA4-Ig gene in the immune cells infiltration and cell apoptosis in murine liver transplantation / 中国普通外科杂志

Objective To investigate the role of B7/CD28 costimulation pathway blockade with adenovirus-mediated CTLA4-Ig gene in macrophage and CD8~+T cell infiltration and cell apoptosis in murine liver transplantation. Methods Rat pairs were divided into three groups: SD-to-Wistar transplantation control group, CsA-treated group and CTLA4-Ig-treated group. IHC and TUNEL were used to analyze the expression of CTLA4-Ig gene in liver and immune cells infiltrate and cell apoptosis in liver grafts. Pathology was done on all harvested grafts. ResultsCTLA4-Ig gene expression was positive in the donor liver on day 7 after administering adenovirus-mediated CTLA4-Ig gene via vein, and remained positive until day 60 after liver transplantation. Infiltration of immune cells in CTLA4-Ig-treated group was less than that in rejection control group. the apoptotic index of rejection group on day 3,5,7 was significantly higher than those of CTLA4-Ig-treated. Conclusions CTLA4-Ig gene was constantly expressed in the donor liver after single intravenousely injection into rats using adenovirus as vector. Adenovirus-mediated CTLA4-Ig gene therapy can inhibit infiltration of immune cells and apoptosis in grafts, thus prolonging the survival of recipients.

Posthepatic manipulative bleeding alleviates lung injury induced by liver ischemia-reperfusion / 中国病理生理杂志

AIM:To determine the effects of posthepatic manipulative bleeding on the lung injury induced by hepatic ischemia-reperfusion (HIR)in rat model. METHODS:Rat 35 min total hepatic ischemia model was used in this study. We treated the experimental rats by posthepatic manipulative bleeding or IH-CV manipulative bleeding at 10 min after reperfusion. RESULTS:Two percent of body weight posthepatic manipulative bleeding with blood transfusion at 10 min after reperfusion significantly decreased circulating malondialdehyde(MDA). Tissue edema,myeloperoxidase(MPO) and MDA concentrations in lung were significantly decreased 6 h after treatments. The 7 d survival rate was remarkably improved in experimental group. CONCLUSION:Two percent of body weight posthepatic manipulative bleeding with blood transfusion at 10 min after reperfusion significantly protects the rats from lung injury induced by HIR.

Infusion of donor specific bone marrow alleviates acute rejection reaction in liver allotransplantation / 中国病理生理杂志

100 d),and the histological grade of rejection was significantly lower than that in group Ⅱ(P

Intrathymic inoculation of liver specific antigen protects hepatocytes from apoptosis after liver allotransplantation / 中国病理生理杂志

AIM: To study the effects of intrathymic inoculation of liver specific antigen (LSA) on hepatocyte apoptosis after liver allotransplantation. METHODS: Orthotopic liver transplantation was used in this study. Group Ⅰ: syngenic control (Wistar-to-Wistar); Group Ⅱ: acute rejection (SD-to-Wistar); Group Ⅲ: thymus inoculation of SD rat LSA day 7 before transplantation. The observation of general situation and survival time, hepatocyte apoptosis and LAT expression in liver transplants were used to analyze immune state of animals in different groups. RESULTS: The general situation of group Ⅰ was very well after transplantation. Recipients of groupⅡ lost body weight progressively and all died within day 9 to day 13 post transplantation. As for group Ⅲ, the general situation of recipients was remarkably better than that in group Ⅱ. The positive cells of apoptosis in group Ⅲ detected by TUNEL were not significantly different from that in group Ⅰ, but was significantly lower than that in group Ⅱ. LAT was detected at any time in group Ⅱ with peak expression at day 5 and day 7 post transplantation. In contrast, LAT was not detected in any other groups. CONCLUSION: Intrathymic inoculation of LSA protects hepatocytes from apoptosis after liver allotransplantation.

Role of 1,25-dihydroxyvitamin D3 in preventing allograft acute rejection in rat orthotopic liver transplantation / 中国普通外科杂志

Objective To study the role of 1,25-dihydroxyvitamin D3 in preventing allograft acute rejection in rat orthotopic liver transplantation. Method Rats receiving orthotopic liver transplantation were divided into groupⅠ: syngenic control (Wistar-to-Wistar); GroupⅡ:acute rejection (SD-to-Wistar). GroupⅢ: acute rejection treated with cyclosporine; GroupⅣ: acute rejection treated with 1,25-(OH)_ 2 D_ 3 . Liver function, rejection index and IFN-? mRNA, IL-10 mRNA expression level were monitored on d1,5,7,15,30 posttransplantation. Results Survival of recipients in group Ⅳ was significantly prolonged (vs group Ⅱ, P

Mechanism by which cyclosporine A downregulates transcription of interferon-? gene after orthotopic liver transplantation in rats / 中国普通外科杂志

ObjectiveTo investigate the mechanism by which cyclosporine A downregulates transcription of interferon-? gene after murine orthotopic liver transplantation.Methods Orthotopic murine liver transplantation model was employed and rats were divided into 3 groups. GroupⅠ: syngeneic control (Wistar-to-Wistar); GroupⅡ: acute rejection (SD-to-Wistar). GroupⅢ: acute rejection treated with cyclosporine A (SD-to-Wistar+CsA). EMSA was employed to analyze NFAT and NF-?B DNA-binding activity of splenocytes, RT-PCR was employed to analyze IFN-? mRNA transcription intragraft on 1,3,5,7,12 day posttransplant in each group, respectively. Histopathological examination was also performed for reference.Results In comparison to groupⅠ, NFAT and NF-?B DNA-binding activity of splenocytes in groupⅡincreased significantly( P

Role of NFAT in CsA downregulating IFN-? gene transcription after liver transplantation* / 中国病理生理杂志

AIM: To investigate the role of NFAT in cyclosporine A downregulating IFN-? gene transcription after liver transplantation. METHODS: Rat orthotopic liver transplantation model was employed and 3 groups of experiments were performed in this study. GroupⅠ: syngeneic control (Wistar-to-Wistar); GroupⅡ: acute rejection (SD-to-Wistar). GroupⅢ: acute rejection treated with cyclosporine A intramuscularly (SD-to-Wistar+CsA). EMSA and RT-PCR were used to analyze NFAT activity of splenocytes and IFN-? gene transcription intragraft of recipients with or without CsA treatment after liver transplantation. Histopathological assessment was also performed for reference. RESULTS: No noticeable rejection was detected in GroupⅠ while only low level of IFN-? mRNA transcription and faint NFAT activity were measured. In contrast, a marked rejection reaction was demonstrated from day3 postoperation in GroupⅡ. IFN-? mRNA transcription was significant and NFAT activity was intensive. In comparison to GroupⅡ, rejection grade in Group Ⅲ significantly decreased (P

Inhibitory effect of EGCG on proliferation and HIF-1?/VEGF expression in cell line HepG2 / 中国病理生理杂志

AIM:To study the molecular mechanism of EGCG on inhibiting the growth of hepatic carcinoma. METHODS: The proliferation of hepatic cell line HepG2 cultured with different doses of EGCG was studied by MTT and suspension/adherence methods. The effect of EGCG on the expression of HIF-1?/VEGF at mRNA and protein levels in vitro and in vivo was evaluated by RT-PCR and Western blotting,respectively. The inhibition of EGCG on the growth of tumor implanted into athymic nude mice was also observed. RESULTS: The proliferation of hepatic cell line HepG2 was inhibited by EGCG in a dose-dependent manner. The expression of HIF-1?/VEGF was suppressed markedly by EGCG at protein level. However,the inhibitory effect of EGCG on the mRNA expression was only observed on VEGF,not on HIF-1?. In the animal experiment,the implanted tumor growth was inhibited by 39.8%?5.1%. CONCLUSION: EGCG suppresses the hepatic carcinoma cell growth,and interrupts the HIF-1?/VEGF signaling pathway significantly,indicating a fundamental mechanism of EGCG for inhibiting tumor growth.