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Objective:To establish donor liver quality related risk factors for the loss of function of transplanted liver.Methods:The data of donors and recipients of liver transplantation at the Organ Donation and Transplantation Center of the First Affiliated Hospital of Sun Yat-sen University from Nov 2011 to Dec 2018 were analyzed retrospectively. Propensity score matching (PSM) was performed to evaluate and screen the data of donors and recipients, in order to balance the covariates.Results:Of the organ donation, there were 70 males and 20 females , aging (40.6±16.3) years. Of the liver transplantation recipients, there were 70 males and 20 females , aging (41.8±20.3) years. Liver dysfunction after transplantation was significantly correlated with the following variables: the donor's CPR time( t=0.429, P=0.000), 15-minute retention rate of indocyanine green ( χ2=67.151, P=0.000), liver function grading ( χ2=54.154, P=0.000), bullae fatty liver grading ( χ2=8.120, P=0.017), vesicular fatty liver grading ( χ2=16.000, P=0.001), ICU stay time ( χ2=14.900, P=0.001)and serum creatinine level ( χ2=44.685, P=0.000). The donor scoring system was established in our studying. For the 90 organ donation cases, the donated liver quality were classified into four levels,which were of good correspondence to the prognosis of the recipients. Conclusion:This donor scoring system and grading standards established by analyzing the high-risk factors of liver dysfunction after transplantation helps evaluate the quality of donor liver in China.
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Objective To study the expression of MREll-RAD50-NBS1 complex in normal gallbladder tissues,simple cholecystitis,calculous cholecystitis and gallbladder carcinoma.Methods The expression of MRN complex in different gallbladder lesion tissues were detected by immunohistochemistry.Western blot,Methyl thiazolyl tetrazolium(MTT) assay and flow cytometry were used to detect the influence of apoptosis and proliferation induced by NBS1.Results The differences between the expression of MRE11,RAD50 and different gallbladder lesion tissues were not statistically significant (respectively x2 =2.724,1.697,all P ＞ 0.05).The expression of NBS1 in GBC tissues [15.3％ (9/59)] was prominently lower than that in the normal gallbladder tissues [84.7％ (50/59)],simple cholecystitis [87.8％ (36/41)],calculous cholecystitis [61.2％ (30/49)] (x2 =87.388,P ＜ 0.01).The Western blot results reveal that NBS1 can mediate apoptosis by up-regulate Bax and down-regulate Bcl-2.The MTT assay results showed that the relative absorbance of treatment and control group after 24,48,72 h were[(1.120 ± 0.006)vs.(1.350±0.009),(1.600±0.004)vs.(1.99±0.01),(1.83±0.01)vs.(2.260±0.003)(F=7.659,P ＜0.01).The apoptosis rate in treatment group(17.23％ ± 0.56％)was higher than that in the control group (4.13％ ± 0.67％) (t =9.133,P ＜ 0.01).Conclusion NBS1 is closely related to gallbladder carcinoma.NBS1 can inhibit the proliferation and promote apoptosis of GBC-SD cells.
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Objective To study the expressions of Nodal in normal gallbladder,and gallbladders with cholelithiasis,cholecystitis and carcinoma;and to study the impact of inhibiting or promoting Nodal expressions in gallbladder carcinoma on the Smad2/4 pathway and epithelial-mesenchymal transition.Methods Immunohistochemistry was used to detect the expressions and distributions of Nodal protein in 30 normal gallbladders,96 simple cholecystitis/calculous cholecystitis specimens and 42 gallbladder carcinoma specimens.The mRNA and protein expressions of Nodal in normal and malignant gallbladdcr mucosal epithelium cells and breast cancer cells were detected by RT-PCR,western blotting and wound healing tests.The impact of activating agents and inhibitors on the expression levels of Nodal and its signaling pathway Smad2/4 and EMT-related proteins were analyzed.Results Immunohistochemistry showed that the positive rates of Nodal in the gallbladder cancer group was significantly higher than that in the gallbladder stone group and the normal gallbladder group.The results were 83.3％ (35/42),44.8％ (43/96),6.7％ (2/30) respectively (P＜ 0.01).RT-PCR and Western blotting showed the expressions of Nodal in gallbladder carcinoma cells were higher than normal gallbladder cells (P＜0.05).After using rhNodal to up regulate the Nodal expression,the Smad2 protein phosphorylation was promoted and the EMT associated proteins were up-regulated.After using the inhibitor SB431542 to suppress the Nodal expression,the Smad2 protein phosphorylation decreased and the EMT associated proteins were down-regulated.Conclusions The expression of Nodal was closely related to cell proliferation and metastasis in gallbladder carcinoma.Tumor progression was promoted via the smad2/4 pathway through epithelial-mesenchymal transition.
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Objective To investigate the expressions of Yes-associated protein-1 (YAP1) in gallbladder mucosal epithelium of normal persons,in patients with simple/calculous cholecystitis,and in patients with gallbladder carcinoma;and to study the mechanism of YAP1 in gallbladder carcinoma development.Methods Immunohistochemistry was used to detect the expression and distribution of YAP1 protein in 50 persons with normal gallbladder,101 patients with simple cholecystitis/calculous cholecystitis and 100 patients with gallbladder carcinoma.RT-PCR and western-blot were used to detect the mRNA and protein levels of YAP1 in normal and malignant gallbladder mucosal epithelium cells.siRNA was used to shut down the expression of YAP1 in SGC996 cells.MTT was used to test cell vitality.Flow cytometry was used to measure cell cycle.Results Immunohistochemistry revealed the expression rates of YAP1 in the gallbladder carcinoma group,the cholecystitis/gallstone group and the control group to be 87.0％ (87/100),56.4％ (57/101) and 5.0％ (1/20),respectively (P ＜ 0.01).The YAP1 protein levels were higher in gallbladder carcinoma tissues and cells when compared to normal tissues and cells.RT-PCR showed the mRNA levels of gallbladder carcinoma cells to be 12.5 ± 1.2 times of normal gallbladder mucosal epithelial cells (P ＜ 0.05).After using siRNA to shut down the YAP1 expression,EMT associated proteins were down-regulated,cell vitality was decreased,and cell cycle was arrested in the S-phase.Conclusions YAP1 is closely related to cell proliferation and metastasis of gallbladder carcinoma.It may promote tumor progression through epithelial-mesenchymal transition.transition;Tumor progress
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Objective To analyze the incidence of BK virus (BKV) infection after kidney transplantation in our center and to evaluate the efficacy and safety of conversion treatment with Mizoribine (MZR) on BKV infection after kidney transplantation.Methods The information of recipients who received BK virus screening in hospital or outpatient during 2015-02 to 2016-12 in our center was retrospectively analyzed.The recipients positive for BKV were divided into experiment group (given conversion treatment with MZR) and control group (not given MZR conversion) according to the inclusion criteria.The negative rate of BKV,AR,hyperuricemia and the function of renal allograft during the conversion treatment with MZR were observed.Results 182 recipients accepted BKV screening during 2015-02 to 2016-12 and 68 cases were positive.The positive rate of BKV was 38.5 ％.The positive rate of peripheral blood specimens and midstream urine specimens was 7.1％ and 36.8％ respectively.Twelve recipients were positive for BKV in both peripheral blood specimens and midstream urine specimens.There were 27 recipients in experiment group and 36 cases in control group.Fourteen recipients positive for BKV became negative after MZR conversion in experiment group and the negative rate was up to 51.9％.The mean time of negative rate was 3.2 ± 2.7 (1-10) months after MZR conversion.During the conversion treatment with MZR,AR occurred in 1 case and was reversed by the impact therapy with Thymoglobulin in experiment group.The value of serum uric acid was maintained stable before and after MZR conversion under the action of uric-acidlowering drug.The renal function was kept stable in both experiment group and control group after renal transplantation.No deaths and renal allograft failure cases occurred in both groups during the research period.The 2-year survival rate for patients and kidneys was both 100％.Conclusion The incidence of BKV infection after kidney transplantation was high and the treatment scheme of MZR conversion was safe and effective.
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Myeloid derived suppressor cell (MDSC) is a kind of myogenic stem cells that are induced by tumor-derived cytokines.MDSCs not only have their own immunosuppressive effects,but also can mediate the immunosuppressive effects of T lymphocytes through different mechanisms.Recent studies have shown that MDSCs involved in tumor immune escape,immune tolerance as well as other pathological processes,and played an important role in promoting the generation and development of tumors.The advances of the generation,immunosuppressive effects of MDSCs and their relation with digestive system tumors were summarized in this paper,which would provide evidences for the clinical use of MDSCs in treating digestive system tumors.
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Objective To evaluate the value of urinary normal and modified nucleosides in the diagnosis of primary gallbladder carcinoma.Methods Between March 2011 to September 2012,28 patients with primary carcinoma of the gallbladder (PCG) were included in this study.Spontaneous urine samples were collected and 10 kinds of urinary nucleosides in the sample were determined by reversed-phase high performance liquid chromatography method.Another 62 patients with benign gallbladder disease and 70 healthy volunteers were enrolled as controls.Routine clinical tumor markers,including serum CA19-9 and CA125 levels of the PCG patients were also evaluated.Results 10 kinds of nucleoside had a good linear correlation (r＞0.99),and the recovery rate was between 87.4％ ～121.5％ range,and the accuracy rate was between 87.7％ ～121.3％,and the RSD of precision was between 1.5％～10.5％ range.In addition to adenosine and cytidine,the mean levels of the rest of the urinary nucleosides in the PCG group were much higher than those of the controls (P＜0.01).Based on principal component analysis,89.3％ of the PCG patients were correctly identified,which was much higher than those detected by CA19-9 (60.7％) and CA125 (67.9％) (P＜0.01).Conclusion Urinary nucleosides may become additional tumor markers which when combined with other clinical methods may help in the screening and early diagnosis of primary gallbladder cancer.
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Gastrointestinal cancer is the most prevalent cancer among malignant tumors,with a upward trend in incidence.Since there is absence of specific clinical manifestation as well as low diagnostic rate,patients diagnosed with cancer of digestive tract are mostly in intermediate or advanced stages.Therefore,they lose the best chance of surgery and have a poor prognosis. Metabonomics,a kind of high sensitivity research technology,shows great potential in the exploration of occurrence and development of malignant tumor.The aim of this study was to review the progress of application in gastrointestinal cancer by metabonomics.
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End stage liver disease is a serious threat to human health.Existing conventional therapies are far from ideal,and orthotopic liver transplantation is limited by the lack of donor liver.A new therapy,transplantation of hepatic stem cell,is a promising approach.Hepatic oval cells are hepatic stem/progenitor cells(HSC/HPC)during hepatic regeneration,and they are being referred to as hepatic precursor cells.It got its name because of its oval nucleus,high nuclear/cytoplasmic ratio and other morphological features.Research has shown increasingly importance in the knowledge of hepatic oval cells.There are many signaling pathways in hepatic oval cells activation and proliferation.As a branch of the Wnt signaling pathway,Wnt/β-catenin signaling pathway has a significant effect on hepatic oval cells activation and proliferation.However,the exact mechanisms of this process have not been completely elucidated.This review describes the role of Wnt/β-catenin signaling pathway in hepatic oval cell activation and proliferation.
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Objective To investigate the expressions of indoleamine 2,3-dioxygenase (IDO) and transcription factor forkhead box P3(FOXP3)in gallbladder adenocarcinoma; and to evaluate the relationship between the expressions of IDO and FOXP3 protein,and clinicopathology and lymph node metastasis of gallbladder carcinoma.Methods The expressions of IDO and FOXP3 in 51 cases of primary gallbladder cancer,90 cases of chronic cholecystitis,and 20 cases of normal gallbladder tissues were studied by immunohistochemical staining. Results The positive expression rates of IDO and FOXP3 in gallbladder carcinoma were 72.5％ (37/51) and 60.8％ (31/51),in normal gallbladder mucosa were 5％ (1/20) and 20.0％ (4/20),in cholecystitis and gallstone were 11.1％ (10/90) and 32.2％ (29/90),respectively.There were significant differences among the three groups in IDO and FOXP3 expressions (P＜0.01).The positive expression rates of IDO and FOXP3 were 7.1％ and 14.3％ for simple hyperplasia,17.7％ and 35.3％ for atypical hyperplasia,40％ and 35％ for gallbladder carcinoma (stages Ⅰ-Ⅲ),and 77.4％ and 64.5％ for gallbladder carcinoma (stages Ⅳ-Ⅴ ).There were significant differences among the four groups in IDO and FOXP3 expressions (P＜0.01).There were significant differences among the Nevin stage groups,lymph node metastasis group and gallbladder stone in IDO and FOXP3 expressions.However,there were no significant differences among the sex groups and the age groups in IDO and FOXP3 expressions (P＞0.05).In gallbladder carcinoma,the expression of IDO had a positive correlation with FOXP3 expression in lymphocyte (γ=0.406,P=0.003).Conclusion In gallbladder cancer,a high-expression of IDO and an expression of FOXP3 in lymphocyte are closely related with immune tolerance of gallbladder carcinoma.The results provide a reference for clinical use of immunotherapy in gallbladder cancer.
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Objective Epithelial mesenchymal transition (EMT) has a role in the proliferation and metastasis of various types of cells.This study investigates the hepatic oval cell's mechanism of EMT induced by histone deacetylase inhibition and the resulting cell motility increase from EMT.Methods Hepatic oval cell stem cell markers and marker changes were detected by flow cytometry,and after histone deacetylase inhibition induced EMT,the morphological changes were recorded.Western blot and quantitative real-time polymerase chain reaction detected the expression of E-cadherin,vimentin and Snail.Furthermore,confocal microscopy analysis recognized the nuclear translocation of Snail.Results Flow cytometry revealed no changes in the stem cell properties of hepatic oval cells in the cell culture process.Oval cell EMT,induced by HDACi,was observed through morphological changes,a reduction of the epithelial cell marker E cadherin,and an increase of the mesenchymal cell marker Vimentin.HDACi can promote the expression and nuclear translocation of Snail,which is the key hepatic oval cell transcription factor for both EMT and enhanced motility.Therefore,Snail RNA interference can suppress HDACi induced EMT in hepatic oval cells.Conclusions In conclusion,histone deacetylase inhibition induces hepatic oval cell epithelial-mesenchymal transition by Snail.
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Objective To investigate the mechanism on JAK/STAT1 signal pathway in SAHA down-regulation of indoleamine 2,3-dioxygenase (IDO) in gallbladder carcinoma cells.MethodsWe treated gallbladder carcinoma SGC-996 cells with IFN-γ and SAHA.Western blotting was used to detect the expression of IDO,signal transducer and activator of transcription 1 (STAT1) phosphorylation and interferon regulatory factor genes-1 (IRF-1).Confocal microscopy analysis was used to detect STAT1 translocation.Transient transfections and reporter genes assay was used in detecting the activation of γ-activated sites (GAS) and interferon stimulated response elements (ISRE).ResultsIDO expressed in SGC-996 cells in dose- and time-dependent manners when stimulated with IFN-γ.SAHA down-regulated the expression of IDO induced by IFN-γ in a dose-dependent manner.SAHA blocked the expression of IRF-1 induced by IFN-γ.SAHA inhibited the IFN-γ-induced STAT1 phosphorylation and nuclear translocation.SAHA down-regulated IFN-γ-induced activation of GAS and ISRE.ConclusionsSAHA may down-regulate IDO expression through inhibiting the activation of members in JAK/STAT1 signal pathway.This may provide a new immunotherapeutic strategy to break tumor immune tolerance in gallbladder carcinoma.
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Objective This retrospective study was to explore the efficacy and determine the risk factors of survival for recurrent hepatocellular carcinoma ( HCC) treated by repeat hepatectomy. Methods From January 1995 till December 2010, 60 patients with recurrent HCCs, were treated by repeat hepatectomy.The significance of seventeen clinical or pathological variables in the risk factors of overall survival were assessed. Results The overall survival 1,3, and 5-year survival rates were 76. 3% , 40.7% and 25. 0% (from repeat hepatectomy), and 95. 0% , 62. 6% and 43. 3% ( from initial hepatectomy) , respectively.Univariate analysis indicated that tumor size at initial hepatectomy, recurrence interval from initial hepatectomy, serum albumin(ALB) level, resection margin, diameter of largest recurrence tumor and rumor vascular invasion were significant prognostic factors(P <0. 05, Kaplan-Meier Log-rank test). Multivariate analysis showed recurrence interval from initial hepatectomy, resection margin, diameter of largest recurrence tumor and rumor vascular invasion were significant prognostic factors(P<0.05, Cox proportional hazards model).Conclusion Repeat hepatectomy is effective for recurrent HCC. Recurrence interval from initial hepatectomy, resection margin, diameter of largest recurrence tumor and rumor vascular invasion were significant prognostic factors.
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Indoleamine 2,3-dioxygenase(IDO)is the rate-limiting enzyme in the catabolism of trypto-phan along the kynurenine pathway.Over expression of IDO is one of the reasons which are responsible for immune tolerance of tumor.IDO also affects the effects of the vaccine of the dendritic cell in the tumor therapy.Lipopolysaccharide(LPS),cytokines and so on can regulate the expression of IDO via different regulating mechanisms.IDO participates in the local immune tolerance of tumor by three kinds of mechanisms.Further research on this immunological regulatory mechanism will be significant for tumor immunotherapy.
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Primary carcinoma of the gallbladder (PCG)is the common malignant tumor in the biliary system.Because there is no specific clinical manifestation, patients diagnosed with PCG are mostlyin intermediate or advanced stages.Therefore, they lose the chance of radical resection of gallbladder carcinoma and have a poor prognosis.Radiotherapy and chemotherapy are not effective palliative measures.Immunotherapy has become an alternative strategy besides operation, chemotherapy and radiotherapy.Treatment with DCs vaccines, as a new method of immunotherapy, has become more and more important.Here we review treatment with DCs vaccines in primary carcinoma of gallbladder.
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Objective Shh and Ptch have been known to play critical roles in the hedgehog pathway and the hedgehog pathway activation occurs in the gastrointestinal cancers. This study was to detect the expression of Shh and Ptch in gallbladder carcinoma, and explore their correlation to gallbladder carcinoma. Methods The expression of Shh and Patch protein in 41 specimens of primary gallbladder carcinoma, 20 specimens of normal gallbladder and 21 specimens of adenoma tissue were assessed by immunohistochemistry.Results The positive expression rate of Shh and Ptch in gallbladder carcinoma was 75.6% (31/41) and 78.0% (32/40) respectively, in normal gallbladder mucous was 5% ( 1/20 ) and 5% ( 1/20 ) respectively,in gallbladder adenoma was 4.7% ( 1/21 ) and 9.6% (2/21) respectively, and there was significant differenee between the three groups in Shh and Patch expression values(P ＜0.001 ). However, there was no significant difference between age group, histological grade group, histologic type group, Nevin stage group,lymph node or distal organ metastasis group, and gallstone presence group in Shh and Ptch expression value (P ＞ 0.05, respectively). The expression of Shh was positively correlated to Ptch (r = 0.72, P ＜ 0.01 ).Conclusion These data support our hypothesis that Hh signaling is dysregulated in human gallbladder carcinognesis.
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Objective To study the expression of chemokine stromal cell-derived factor-1 and its receptor CXCR4 in gallbladder carcinoma and evaluate the relationship between the expression of SDF-1 and CXCR4 protein and the clinicopathology,and lymph node metastasis of gallbladder carcinoma.Methods The expression of SDF-1 and CXCR4 protein in 41 cases of gallbladder adenoma carcinoma was examined by immunohistochemical technique(SP),and the relation of SDF-1/CXCR4 biology axis to clinicopathological parameter was also analyzed.Results The positive expression rate of SDF-1 and CXCR4 in gallbladder carcinoma was 68.3%(28/41)and 51.2%(21/41)respectively,in normal gallbladder mucous was 5%(1/20)and 5%(1/20)respectively,in cholecystitis and gallstone was 6.7%(6/90)and 5.6%(5/90)respectively,and there is significantly different among the three groups in SDF-1 and CXCR4 expression values(P＜0.001,P＜0.001,respectively).There is significant difference among histological grade group,Nevin stage group,histological differentiation,lymph node or distal organ metastasis group in SDF-1 and CXCR4 expression value(P＜0.05,respectively).However,there is no significant difference among sex group,age group,tumor size group,and gallstone presence group in SDF-1 and CXCR4 expression value(P＞0.05,respectively).The expression of SDF-1 was positively correlated to CXCR4(r=0.68,P＜0.01).Conclusion Up-regulated SDF-1 and CXCR4 is associated with the carcinogenesis and metastasis of gallbladder carcinoma.
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Objective To analyze the CT staging and evaluate its role in assessing the resectability of the gallbladder carcinoma.Methods The CT scans of 47 patients who had pathologically confirmed gallbladder carcinoma were retrospectively reviewed and the CT stages of gallbladder carcinoma were used to evaluate the resectability.Results Before operation,three patients were in stage Ⅰ(6.4%,3/47),14stageⅡ(29.8%,14/47),10 stageⅢ(21.7%,3/47),20 stage Ⅳ(42.6%,20/47),however,after operation,three patients were in stage Ⅰ(6.4%,3/47),14 stageⅡ(29.8%,14/47),8 stage Ⅲ(17.0%%,8/47),22 stage Ⅳ(42.6%,20/47).The accurate rate of CT staging confirmed by operation was 91.5%(43/47).The treatment procedures of gallbladder carcinomas included radical operation,palliative excision and exploratory laparotomy.For 47 patients with gallbladder carcinomas,radical operation was performed in 30 cases(3 stage Ⅰ,14 stageⅡ,7 stage Ⅲ,6 stage Ⅳ),palliative excision 15 cases(1 stage Ⅲ,14 stage Ⅳ),exploratory laporatory 2 eases(2 stage Ⅳ).Conclusion The staging of gallbladder carcinoma with CT may provide definite value in evaluating respectability of gallbladder carcinoma.
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0.05). The positive expression rate of p21 and p53 in gallbladder carcinoma was 62.5%(25/40) and 65.0%(26/40) respectively. The expression values of p21 and p53 in chronic cholecystitis was 2.5%(1/40) and 5.0%(2/40) respectively, which was significantly different from that of gallbladder carcinoma ( P
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ObjectiveTo evaluate the changes of Ag-NORs in patients with gallbladder carcinoma.MethodsAg-NORs in the peripheral blood lymphocytes,bile lymphocytes and the mucosa of gallbladder were detected by a cell image analysis of KL-2 in 20 normal volunteers,90 cholecystitis cases, and 20 gallbladder carcinomas. ResultsAg-NORs in peripheral blood lymphocytes (PBL) and bile lymphocytes (BL) in cholecystitis were lower than that in normal group(P