1.Expression and clinical significance of SIRT1 in hepatocellular carcinoma
Zhengyun ZHANG ; Zunqiang ZHOU ; Jiao GUAN ; Hao LI ; Guangwen ZHOU
Chinese Journal of Hepatobiliary Surgery 2014;20(11):790-794
Objective To investigate the clinical significance of silent mating-type information regulation 2 homologue 1 (SIRT1) in hepatocellular carcinoma (HCC).Method We analyzed p53 mutation by gene sequencing and activation of SIRT1 and AMP-actived protein kinase (AMPK) using western-blot in 252 patients with hepatitis B virus-positive HCC.Results A higher proportion of tissues with mutant p53 were demonstrated to harbor activated SIRT1 (64.8% vs 31.8% ; P < 0.01).Activated SIRT1 predicted a longer relapse-free survival.On multivariate analysis,activated SIRT1 remained significant (OR:0.339,CI:0.160-0.720,P =0.005).Analysis of 252 paired specimens revealed a significant correlation between activated SIRT1 and activated AMPK in HCC tissues harboring mutant p53 (P =0.007).Conclusion SIRT1 exerted anti-carcinogenic effects through the AMPK pathway in HCC in the context of mutant p53.
2.Surgical strategy for gastric cancer patients complicating portal hypertension
Yin ZHU ; Zhengyun ZHANG ; Zunqiang ZHOU ; Jun YANG ; Guangwen ZHOU
Chinese Journal of General Surgery 2016;31(2):89-92
Objective To evaluate the outcome of surgical approaches in patients of gastric cancer with portal hypertension.Methods The clinical data of 80 patients with portal hypertension undergoing curative surgery for gastric cancer or simultaneous surgery for portal hypertension were retrospectively analyzed.Results The radical gastrectomy alone had no tremendous impact on postoperative liver function.But simultaneous surgery for portal hypertension affected patients' liver function dramatically (P =0.018).For those who underwent surgery for portal hypertension simultaneously,the incidence of complications in Child B patients was much higher than that in Child A patients (P =0.018).However,the incidence of complications did not differ between Child A and B patients who underwent radical gastrectomy alone.In addition,patients undergoing simultaneous surgery for portal hypertension had more severe complications than those who underwent radical gastrectomy only (P =0.042).Age > 50 (P =0.012),tumor stage (P =0.015),and simultaneous surgery for portal hypertension (P =0.007) were the independent risk factors for postoperative liver dysfunction.The survival time of patients undergoing simultaneous surgery for portal hypertension was significantly shorter than that of patients undergoing radical gastrectomy only (in Child A patients,P =0.009,in Child B patients,P =0.000).Conclusions Individualized surgical approaches for the treatment of gastric cancer with portal hypertension should be decided by preoperative liver function.Simultaneous management of portal hypertension was not recommended.
3.Clinical efficacy of complex splenectomy in 235 patients
Jiao GUAN ; Zunqiang ZHOU ; Danian TONG ; Zhengyun ZHANG ; Guangwen ZHOU
Chinese Journal of Digestive Surgery 2016;15(7):680-683
Objective To explore the clinical efficacy and safety of complex splenectomy.Methods The retrospective cohort study was adopted.The clinical data of 235 patients including 135 from Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine,67 from Shanghai Jiaotong University Affiliated First People's Hospital,26 from Shanghai Jiaotong University Affiliated Sixth People's Hospital,7 from 85 Hospital of PLA who underwent complex splenectomy from January 2005 to December 2015 were collected.All the patients received total splenectomy after splenic artery ligation.The observation indexes included:(1) surgical situations,(2) major complications including intraperitoneal hemorrhage,pulmonary complication,left subphrenic abscess and peritoneal effusion,(3) follow-up situations:portal vein (PV) complications (splenic venous thrombophlebitis,thrombosis of splenic vein and main portal vein thrombosis),survival of patients.The follow-up using outpatient examination and telephone interview was performed up to March 2016,and patients received regularly ultrasound reexamination,computed tomography (CT) rescan,routine blood retest and coagulation function.Measurement data with normal distribution were presented as-x ± s,and count data were analyzed using the chisquare test.Results (1) Surgical situations:of 235 patients,200 patients underwent secondary spleen pedicle severance and 35 patients underwent non-secondary spleen pedicle severance.Volume of intraoperative blood loss and duration of splenic resection were (268 ± 103) mL and (82 ± 29) minutes.(2) Major complications:of 31 patients with postoperative complications,intraperitoneal hemorrhage was detected in 12 patients,pulmonary complication in 17 patients,left subphrenic abscess in 3 patients and massive peritoneal effusion in 21 patients.Some patients were combined with multiple symptoms.The patients with above complications were cured after reoperations and non-operative treatments.(3) Follow-up situations:PV complications:splenic venous thrombophlebitis was detected in 16 patients,thrombosis of splenic vein in 17 patients,thrombosis of splenic vein combined with main portal vein thrombosis in 7 patients,and they were improved after the treatments of antiinflammation,anti-coagulation and thrombolysis.The thrombi rate after splenectomy was 32.4% (12/37) in patients with schistosoma-related cirrhosis and 8.1% (12/149) in patients with HBV-related cirrhosis,with a statistically significant difference (x2 =10.9,P < 0.05).Survival of patients:of 235 patients,228 were followed up for (7.9 ± 4.2) years,with good survival.Conclusion Complex splenectomy is safe and effective,and the key procedure determining the safety of complex splenectomy includes careful preoperative evaluation,delicate surgical technique,proper splenic pedicle severance and peritoneal wounds.
4.Surveillance on endemic situation of schistosomiasis in national surveillance sites of Chongqing City in 2006
Chengguo WU ; Xingjian LUO ; Xin ZHOU ; Bangzhong XIAO ; Zhengyun SI
Chinese Journal of Schistosomiasis Control 1989;0(01):-
Objective To understand the correlative factors of impacting schistosomiasis prevalence so as to provide the scientific evidence for drawing up the control project in Three Gorges Reservoir areas.Methods The report system of schistosomiasis was set up,and the cases were investigated.The population were screened by indirect haemagglutination test(IHA),and the serum-positive people were examined with Kato-Katz technique.The livestock and plants imported from the schistosomiasis endemic areas were investigated.Results Eighty-eight floating people returning from schistosomiasis endemic areas and 107 floating persons from endemic areas were investigated,and the serum positive rates were 1.14% and 1.87%,respectively.No schistosome eggs were found in stool examinations.There was no livestock and plant imported from schistosomiasis endemic areas.The production of local inhabitants depended on mainly cattle,and the river water contact was popular.Conclusions There are infection resources of schistosomiasis imported from endemic areas,which has a potential risk of schistosomiasis prevalence.
5.SIRT1 differently regulates oncogenesis by diverse p53 types in hepatocellular carcinoma
Jiao GUAN ; Zhengyun ZHANG ; Zunqiang ZHOU ; Hao LI ; Shuyun WANG ; Guangwen ZHOU
Chinese Journal of General Surgery 2014;29(5):378-381
Objective To understand how SIRT1 differently regulates oncogenesis in hepatocellular carcinoma (HCC) with wild type and mutant type p53.Methods HCC cell line PLC5 cells (249 site mutated p53),and HepG2 cells (wild type p53) were infected with lentivirus containing shSIRT1.Western blotting was used for signaling pathway detection.Cell growth and proliferation assay,colony formation assay and tumor xenograft assay were performed to test the tumor growth ability of HepG2 cells,HepG2-shSIRT1 cells,PLC5 cells and PLC5-shSIRT1 cells respectively.Results SIRT1 silencing resulted in significant inhibition of cell proliferation in HepG2 cells but stimulating cell proliferation in PLC5 cells (t =3.595,P <0.01).Acetylation of p53 was found in HepG2 (HepG2-shSIRT1) and p21 was up-regulated,however,in PLC5 (PLC5-shSIRT1) cells,acetylation of p53 was found but p21 was not induced despite of p53 activation.Silence of SIRT1 resulted in no change of AMPK function in HepG2 cells but a lower activity of AMPK in PLC5 cells (t =4.268,P < 0.01).Conclusions In HCC cell lines the function following SIRT1 activation is largely determined by p53 mutant status.
6.Mechanism of immunotolerence induced by bone mesenchymal stem cell co-transplanted with islets through regulating Tfh in NOD mice
Jiao GUAN ; Zhengyun ZHANG ; Zunqiang ZHOU ; Hao LI ; Danian TONG ; Guangwen ZHOU
Chinese Journal of Hepatobiliary Surgery 2015;21(4):262-265
Objective To study the regulation mechanism of bone mesenchymal stem cell (MSC)combined co-translation of islets in differentiation of Follicular Helper T cell (Tfh),and its roll on immunotolerence induction in non-obese diabetic (NOD) mice transplantation model.Methods The NOD mice were divided into 4 groups:Group A with islet transplantation alone;Group B with MSC co-transplantation with islets (MSC:0.5 × 106);Group C with MSC co-transplantation with islets (MSC:2 × 106);Group D with MSC co-transplantation with islets (MSC:3 × 106).ELISA was used to test the expression level of diabetes autoantibody GAD65Ab and IAA.Tfh cell count was detected by FACS.Results The survival time of transplantation groups was much longer in MSCs co-transplantation group than islet-alone group;the level of GAD65Ab,IAA and Tfh cell count were much lower in MSCs co-transplantation group than islet-alone group.Conclusion MSC may protect the islet transplants by regulating the Tfh cell differentiation.
7.Protective effect of cobalt protoporphyrin-induced the strong expression of heme oxygenase-1 on islet xenotransplant
Zhengyun ZHANG ; Xi CHEN ; Chang SU ; Weiqiong GU ; Hongwei LI ; Guangwen ZHOU
Chinese Journal of Organ Transplantation 2008;29(6):343-345
Objective To analyze the dose-effect relationship between cobalt protoporphyrin (CoPP) and heme oxygenase-1 (HO-1) expression in islets and to investigate the protective effect of strongly expression of HO-1 in islet xenotransplantation. Methods Donor islets isolated and purified from SD rats were randomly divided into 5 groups and incubated with different doses of CoPP for 24 h.Group A: 0 mmol/L; Group B: 5 mmol/L; Group C: 25 mmol/L; Group D: 50 mmol/L; Group E:75 mmol/L. The expression of HO-1 mRNA and protein in islets was detected by RT-PCR and Western blot respectively. Glucose of low and high concentrations was added to islets in vitro to test insulin-releasing function. The optimal dose of CoPP which could induce the strongest HO-1 expression was chosen according to the results. Recipients were randomly divided into 2 groups. Control group received untreated xeno-islets, and the experimental group received islets incubated with optimal CoPP close in vitro. Glycemia and rejection were observed after transplantation daily. Results The expression of HO-1 mRNA and protein in xeno-islets of group D was significantly higher than in other groups (P<0.05). After stimulation of glucose, the insulin concentration in group D was significantly higher than in other groups (P<0.05). The optimal dose of CoPP which could induce the strongest HO-1 expression was 50 mmol/L. The time for normoglyeemia in experimental group was (14.63±1.19) days, significantly longer than that in control group (9.88±2.17)days (P<0.01). Conclusion The strongest expression of HO-1 induced by CoPP in vitro promotes the glucose-stimulated insulin secretion of islets and prolonged the survival of xeno-islet grafts by protecting them from rejection.
8.CoPP induces Ho-1 upregulation in rat islet cells
Chang SU ; Zhengyun ZHANG ; Xi CHEN ; Weiqiong GU ; Mingjun ZHANG ; Qiang ZHANG ; Guangwen ZHOU ; Hongwei LI
Chinese Journal of General Surgery 2008;23(5):372-375
Objective To investigate the effects of peritoneal injection of cobaltic protoporphyrin Ⅸ chloride(CoPP)to induce heme oxygenase-1(Ho-1)upregulation in rat islet cells.Mthods Forty rats were divided into 5 groups by management 24 h before islets isolation:group A received inlzaporitoneal injection with 2.5 ms/ks CoPP,group B with 5 ms/ks CoPP,group C with 7.5 ms/kg CoPP,and group D with 10 mg/kg CoPP.In control group NS was used instead.A modified Goth approach was used for islet isolation.the yield and purity of the islets were assessed.The expression of Ho-1 mRNA and protein were detected by real time-PCR and Western blotting respectively.Islet function was tested by glucose stimulation test.Result Severe damage was found in tlle rats in group C and D.There was no difference in islet yield and purity for group A、B、C and control(P>0.05).Group B had the highest Ho-1 mRNA and protein expression among the 4 groups.Though there was no difference in insulin secretion by low glucose challenge for group A、B and control's islets(P>0.05),when challenged by hish level of glucose,significant deviation was observed.The imulin secretion level was(172.37±16.4)、(187.68±19.93)and(91.25±Conclusion Peritoneal iajection of 5 mg/kg CoPP can significantly enhance the expression of Ho-1 mRNA and protein in tat islet safely and enhance the function of islet when challenged by hish concentration of glucose.
9.The hepatic stellate cells protection for homotransplanted islet cells
Xi CHEN ; Yao WEI ; Qiang ZHANG ; Chang SU ; Zhengyun ZHANG ; Mingjun ZHANG ; Guangwen ZHOU
Chinese Journal of General Surgery 2010;25(5):401-404
Objective To analyze the protection supplied by HSCs in vivo after islet cells homotransplantation. Method Diabetic mice were randomly divided into three groups as diabetic group,islet-transplant group and co-transplant group. 300 islets alone or mixed with HSCs were transplanted under the capsule of the kidney of the diabetic recipients respectively. Blood glucose and the length of normal blood glucose level were recorded and we collected the blood and tissue of islet graft 7 days after transplantation in each group. Blood concentration of TGF-β, TNF-α, IL-1β and IFN-γ were detected by ELISA. The infiltration of lymphocytes was observed by HE staining and immunohistochemieal examination.Result Co-transplant group had a prolonged islet allograft survival for (23.75 ± 8. 96) days, compared with the islet alone of (11.9 ± 6. 92) days. Blood concentration of TGF-β in co-transplant group was (2292.31 ± 5.87) pg/ml, significantly higher than those in simple transplant group (1246.55 ±38.91) pg/ml(P <0.05), there was no differentence in the two groups for TNF-α,IL-1β and IFN-γ.Conclusion HSCs may prolong the islet graft survival by expressing higher level of TGF-β and form a capsule around the graft.
10.Clinical comparative analysis of surgical resection of the pregnancy by hysterotomy and hysterectomy for cesarean scar pregnancy
Zhengyun CHEN ; Li ZHAO ; Asiyan NUSILATI ; Da ZHAO ; Mi ZHOU ; Xinmei ZHANG
Chinese Journal of Obstetrics and Gynecology 2017;52(2):98-102
Objective To assess the indication and safety of surgical resection of the pregnancy by hysterotomy (SRPH) and hysterectomy for cesarean scar pregnancy (CSP). Methods A retrospective study of women with CSP was conducted at the Women′s Hospital, School of Medicine, Zhejiang University, from Jan. 2003 to Mar. 2016. The women underwent SRPH (SRPH group, n=35) and hysterectomy (Hysterectomy group, n=14) were included. The gestational age (GA), size of gestational mass(GM), level of serum β-hCG, previous treatments and clinical outcomes were analyzed. Results The median GA, the mean size of GM, median serum β-hCG level, median amount of blood loss, rate ot blood transfusion, rate of persistent CSP, and rate of motal status in SRPH group versus Hysterectomy group were 66 versus 84 days, (65 ± 22) versus (92±36) mm, 23755 versus 802 U/L, 400 versus 650 ml, 11%(4/35) versus 13/14, 49%(17/35) versus 12/14, 20% (7/35) versus 14/14, respectively (all P<0.05). In SRPH group, median amount of blood loss was 500 ml in patients with GA≥10 weeks versus 300 ml in patients with GA<10 weeks (P<0.05). Serious complication occurred in 7 patients: severe pelvic inflammation in 1 patient and hematomas in the uterine isthmus in 1 patient in SRPH group; severe pelvic inflammation in 2 patients and hemorrhagic shock and DIC in 3 patients in Hysterectomy group. No blaader damage occurred. Conclusions SRPH is effective and safe for patients with CSP with GA of 9-10 weeks, a diameter of 60-90 mm and stable hemodynamics. Hysterectomy is an alternative to SRPH for patiens in motal status with advanced GA more than 12 weeks.