1. FXR agonist GW4064 ameliorates tacrolimus-induced abnormalities in glucose metabolism
Hao LI ; Ling LI ; Zhiping XIA ; Qifa YE ; Guizhu PENG ; Qifa YE
Chinese Journal of Clinical Pharmacology and Therapeutics 2022;27(4):466-472
AIM: To investigate the expression of glucose metabolism genes associated with tacrolimus-induced post-transplant diabetes in the mouse kidney and the mechanisms involved in the regulation of glucose metabolism by farnesylate X (FXR) receptor activator. METHODS: The gene expression levels of FXR, small heterodimeric partner-1 (SHP-1), phosphoenolpyruvate carboxykinase (PEPCK), and glucose transporter protein-2 (GLUT2) were measured after 72 h in HK-2 cell lines treated with tacrolimus and tacrolimus+FXR agonist (GW4064) and control groups, respectively. C57BL/6J male mice were gavaged with tacrolimus and tacrolimus+FXR agonist for 12 weeks, respectively, and the control group was given saline to observe the changes in body weight and blood glucose; after the animals were treated, the gene expression levels of FXR, SHP-1, PEPCK, and GLUT2 were detected, respectively. RESULTS: In cellular experiments, the expression of FXR, SHP-1 and GLUT2 genes was decreased in the tacrolimus-treated group (P< 0.05) and the expression of the PEPCK gene was significantly upregulated compared with the control group (P< 0.05). In animal experiments, compared with the control group, the blood glucose values were significantly increased in the tacrolimus-treated group and significantly decreased in the tacrolimus+FXR agonist combination intervention group (P< 0.05), and the expression of FXR, SHP-1 and GLUT2 genes were upregulated (P< 0.05) and the expression of PEPCK genes was significantly decreased in the mice kidney (P< 0.05).CONCLUSION: FXR agonists can improve tacrolimus-induced abnormal glucose metabolism after transplantation. Therefore, FXR may be a potential new target for the prevention and treatment of post-transplant diabetes.
2.Effect and potential molecular mechanism of FOXA2 on cell proliferation, migration and invasion of hepatocellular carcinoma
Zhongshan LU ; Xiaoyan HU ; Wei WANG ; Qifa YE ; Guizhu PENG
Chinese Journal of Hepatobiliary Surgery 2021;27(9):694-698
Objective:To investigate the effect of forkhead box protein A2(FOXA2) on cell proliferation, migration and invasion of hepatocellular carcinoma and the potential molecular mechanism.Methods:From January 2019 to December 2020, 10 cases of hepatocellular carcinoma patients from Zhongnan Hospital of Wuhan University were collected for study, including 7 males and 3 females, with an average age of 53 years. FOXA2 expression was detected in human liver cancer cell line, and the highest expression of FOXA2 was found in HepG2 cells transfected with FOXA2 overexpression plasmid. Immunohistochemistry and qRT-PCR were used to detect the expression of FOXA2. Western blot was used to detect the expression of FOXA2, hypoxia-inducible factor-1 α (HIF-1α), vascular endothelial growth factor A (VEGFA), B-cell lymphofactor-2 (Bcl-2), matrix metalloproteinase (MMP) 7, and glucose transporter (GLUT) 1. EdU assay was used to study cell proliferation, and Transwell chamber assay was used to study cell migration and invasion.Results:The relative expression of FOXA2 in liver cancer tissues were lower than those in adjacent tissues both at mRNA and protein levels, with statistical significance (both P<0.05). FOXA2 overexpression group showed lower cell proliferation rate (30.0±3.2)%, migration rate (10.6±1.1), and invasion rate (12.8±0.8) comparing with negative control group (67.0±3.6)%, (81.0±5.4), (74.8±4.5). The difference was statistically significant (all P<0.05). Expression of HIF-1α and its downstream targets VEGFA, MMP7, GLUT1 and Bcl-2 was decreased after over-expression of FOXA2 in HepG2 cells. Conclusion:FOXA2 inhibits proliferation, migration, and invasion in hepatocellular carcinoma by regulating HIF-1α signaling pathway, suggesting that FOXA2 is a potential target for the treatment of hepatocellular carcinoma.
3.Clinical retrospective analysis in delayed graft function morbidity of kidney transplantation recipients and gender factors in both donors and recipients
Dawei ZHOU ; Juntao LIANG ; Yanfeng WANG ; Guizhu PENG ; Shaojun YE ; Zhiping XIA ; Xiaoyan HU ; Qifa YE
Chinese Journal of Organ Transplantation 2019;40(7):414-418
Objective To explore the effects of donor/recipients' gender on delayed graft function (DGF) .Methods A retrospective analysis was performed for clinical data of donors (n=174) and recipients (n=265) during renal transplantation between May 1 ,2012 and December 31 ,2017 . Types of China donation after citizen's death ,age ,last creatinine level ,height ,weight ,body mass index (BMI) and protopathy of donors were collected .And pre-dialysis method ,dialysis time ,HLA mismatch ,post-creatine at Day 7 ,whether dialysis after transplantation ,height ,weight and BMI of recipients were analyzed .The data were checked by t and chi square tests and P<0 .05 was deemed as statistically significant .Results Donor gender had no correlation with DGF occurrence rate ( P=0 .689) while DGF occurrence rate among female recipients was evidently lower than that among males (P=0 .036);Female recipients selected peritoneal dialysis therapy more than male recipients (P=0 .023);Cerebral hemorrhage female donors were more than male donors (P= 0 .034);BMI (P<0 .001) and postoperative creatinine (P= 0 .001) among female recipients were evidently lower than that among males .Conclusions DGF occurrence rate is significantly lower among female receptors than that among males after kidney transplantation .
4. Advances in intervention measures for hepatic ischemia-reperfusion injury
Zhongshan LU ; Wei WANG ; Zibiao ZHONG ; Qifa YE ; Guizhu PENG
Chinese Journal of Hepatobiliary Surgery 2019;25(11):871-874
Hepatic ischemia-reperfusion injury is an inevitable clinical phenomenon during the liver transplantation. The mechanism of hepatic ischemia-reperfusion injury is complex, with reactive oxygen species, inflammatory factors, calcium overload, neutrophils and Kupffer cells involved. If injury continues to getting worsen, liver cells will undergo necrosis, apoptosis, and autophagy. Interventions for hepatic ischemia-reperfusion injury mainly include ischemic preconditioning, drug pretreatment, chemical pretreatment, mild hypothermia pretreatment, and machine perfusion and gene-targeted therapy in recent years. With the indepth research of injury mechanism, new intervention methods continue to emerge, which will bring new ideas for clinical prevention and treatment of liver ischemia-reperfusion injury.
5.Clinical values of preemptive therapy versus universal prophylaxis in the prevention of cytomegalovirus infection post kidney transplantation: a systematic review and Meta-analysis
Lei WANG ; Guizhu PENG ; Qifa YE
Chinese Journal of Urology 2018;39(4):294-299
Objective To evaluate the clinical efficacy of preemptive therapy versus universal prophylaxis in prevention of cytomegalovirus (CMV) infection post kidney transplantation.Methods Databases including the PubMed,EMbase,sinoMed,Web of Knowledge,the Cochrane Central Register of Controlled Trails (CENTRAL) and other databases were searched up to December 2016 for controlled clinical studies which involved preemptive therapy and universal prophylaxis.Odds ratio (OR) and mean difference (MD) with 95% confidence interval (CI) was performed using Review Manager 5.3 software to synthesize the results.Results 11 studies with a total of 2 560 patients were included in this Metaanalysis.Results showed that universal prophylaxis was superior to preemptive therapy in the total CMV infection and CMV disease(OR =3.38,95% CI 2.13-5.36,P <0.001;OR =1.69,95% CI 1.14-2.48,P =0.008),otherwise it was on the contrary in the late onset CMV infection and CMV disease (OR =0.07,95% CI0.02 ~0.19,P < 0.001;OR =0.08,95% CI 0.01-0.60,P =0.01).However,there was no significance in the short outcomes between the two groups including 1-year recipient and graft survival and renal function.In addition,preemptive therapy was superior to universal prophylaxis in the adverse events (OR =0.33,95 % CI 0.15-0.72,P =0.006).Conclusions There was no significant difference between the two prophylaxis in the prevention of CMV infection,but preemptive therapy was superior to universal prophylaxis in the prevention of anti-virus adverse effects.
6.Comparison of gender differences in the rat model of fluorosis
Yang LIU ; Lunying HAN ; Chuan HE ; Fengtao PENG ; Guizhu LI ; Feiqing WANG
Chinese Journal of Comparative Medicine 2018;28(1):33-37
Objective To construct the male and female rat model of fluorosis and to explore the gender difference in fluorosis. Methods A total of 48 clean-grade SD rats with the body weight of about 150 g (male∶female=1∶1) were equally divided into the control group and fluorosis model group. Rats in the fluorosis model group were fed with fluorine-containing (100 mg/kg) feedstuff. The general condition, changes in body weight and dental fluorosis of the rats were observed every three days. A batch of female and male rats were sacrificed by femoral artery bleeding on the 70th and 110th day of experiment, respectively, when all rats showed dental fluorosis. The levels of urinary fluoride and bone fluoride of the rats were measured by a fluoride ion-selective electrode. Results All the male and female rats in the control group did not show dental fluorosis during the entire experiment. The female and male rats in the fluorosis group showed dental fluorosis visible to naked eye began approximately on the 60th and 80th day, respectively, indicating that the appearance of dental fluorosis of the male rats was about 20 days later than the female rats. After 30 days or so, the male and female rats went into a rapid growth period, and there were significant differences between the body weights of the male and female rats (P< 0. 01). The body weight of the male and female rats in the fluorosis group was higher than that of the control group on the 110th day. With the progression of fluorosis, the levels of urinary fluoride and bone fluoride of the rats were gradually increased, and finally significantly higher than those of the control group (P< 0. 01). There was a positive correlation between the levels of urinary and bone fluoride and the time of fluorosis. The levels of urinary and bone fluoride of the male rats were significantly higher than those of the female rats (P< 0. 01), indicating that they are affected by gender. Conclusions The body weight of the rat model of fluorosis, the starting time when dental fluorosis occurs and the levels of urinary and bone fluorine are all different between male and female rats.
7.Comparison of three types of china donation after citizen's death in clinical efficacy and complications after liver transplantation: a report of 422 cases
Qifa YE ; Qianchao HU ; Yingzi MING ; Yanfeng WANG ; Ke CHEN ; Shaojun YE ; Guizhu PENG ; Zibiao ZHONG ; Yi ZHANG ; Zhiliang WANG ; Yujun ZHAO ; Jing SI
Chinese Journal of Organ Transplantation 2017;38(7):408-413
Objective To compare three different types of donor livers (C-Ⅰ,C-Ⅱ,C-Ⅲ) in clinical efficacy,complications and survival rate of liver transplantation.Methods Using the retrospective descriptive study method,the clinical data of 422 patients undergoing liver transplantation,including 124 cases of C-Ⅰ,81 cases of C-Ⅱ and 81 cases of C-Ⅲ in recent 6 years (from June 2010 to June 2016) were analyzed.The same surgical method was performed with piggyback liver transplantation.Observation indicators contained (1) recipient postoperative liver function;(2) the postoperative complications;(3) the recipient survival rate.SPSS 19.0 statistical software was used for analysis.Results (1) The curative effect was evaluated by the changes of ALT and TBIL among three groups of recipients postoperatively.As compared with C-Ⅰ transplantation group and CⅢ transplantation group,the level of ALT in C-Ⅱ transplantation group was significantly increased (P <0.05),the clinical efficacy was poorer.(2) The incidence of PNF was 3.23% in C-Ⅰ group,9.88% in C-Ⅱ group and 9.88% in C-Ⅲ group (P<0.05).The incidence of acute rejection was respectively 9.68% in C-Ⅰ group,38.27% in C-Ⅱ group and 38.27% in C-Ⅲ group (P<0.001).The incidence of SIRS was respectively 5.65% in C-Ⅰ group,39.50% in C-Ⅱ group and 39.50% in C-Ⅲ group (P< 0.001).There were significant differences in the incidence of other complications among the three groups.(3) There were 14 deaths within 3 months,accounting for 17.28%,and the survival rate was 82.72% in C-Ⅱ group,the 1-,3-,and 5-year survival rate was 76.55%,74.18% and 76.55% respectively in C-Ⅰ group,and that was 88.02%,85.72% and 81.11% respectively in C-Ⅲ group.Conclusion Since June 2015,C-Ⅰ donors grow up more quickly on year-on-year basis than C-Ⅱ.Simultaneously,the sort-term and long-term clinical efficacy is better in C-Ⅰ transplantation group than in C-Ⅱ transplantation group.How to repair the three types of Chinese standard donor organs and optimize the quality is still a hot point to ensure the healthy development of organ transplantation in China,which needs further investigation.
8.Study of 66 liver transplantations from donation after brain death
Qifa YE ; Qiuyan ZHANG ; Yanfeng WANG ; Shaojun YE ; Guizhu PENG ; Yingzi MING ; Xiaoli FAN ; Zibiao ZHONG
Chinese Journal of Organ Transplantation 2017;38(1):24-29
Objective To sum up the experiences in liver transplantations from donation after brain death (DBD),and compare the clinical effect,complications and influential factors with international situation.Methods The retrospective descriptive study was adopted.All the data of 66 DBD liver donors and the matched recipients from authors' affiliations during June 2010 and June 2013 were collected.Original articles,meta-analysis and data reports with high academic influence were read and data were analyzed with SPSS 22.0.Results The incidence of serious complications,vascular complications and biliary complications during the first year among 66 recipients was 21.2%,10.6%,and 6.1%,respectively.Compared to international situation,graft 1-,3-,and 5-year survival rate was similar (P>0.05) (83%,80% and 73% respectively),similar to that of recipients.There was no statistically significant difference in primary nonfunction and vascular complications between our center and other centers.As for biliary complications,morbidity was lower in our center (P<0.05).The 3-and 5-year survival rate of recipients was also similar (P>0.05),though the 1-year survival rate was slightly lower (P< 0.05).Conclusion These findings provide evidence that patient's prognosis under DBD liver transplantation in our center is acceptable,and long-term survival rate has reached international level.Still,1-year survival rate of recipients is unsatisfactory.In order to achieve a good clinical efficacy,we need to find out disadvantages during donor maintenance,recipient selection,surgical procedure and postoperative management.
9.Research progress on the application of human hepatitis B immunoglobulin in preventing hepatitis B recurrence after liver transplantation
Lei WANG ; Lin FAN ; Guizhu PENG ; Qifa YE
Chinese Journal of Hepatobiliary Surgery 2017;23(7):494-498
Patients who suffer from HBV-related endstage liver disease are the majority of liver transplantation (LT) recipients,and hence HBV recurrence post-LT is the key for the treatment success.HBIG was no longer solely used in clinical practice because of high cost and unavoidable drug-resistance.Nowadays,the standard prophylaxis regimen is the combination of low-dose HBIG and nucleoside analogues (NAs).Recently,the necessity of HBIG usage has been often questioned,and the novel prophylaxis of HBIG-withdrawn and HBIG-free regimen have been carried out in several transplant centers with encouraging results.In this review,we summarized the application of HBIG in the prophylaxis of HBV recurrence,and then evaluated the prospect of the prophylaxis of HBIG-withdrawn and HBIG-free regimen.
10.Meta-analysis of the risk factors of urinary tract infection after renal transplantation
Mingxia LI ; Guizhu PENG ; Xianpeng ZENG ; Yanfeng WANG ; Ling LI ; Zhiping XIA ; Qifa YE
Chinese Journal of Organ Transplantation 2016;37(3):159-164
Objective To determine the risk factors of urinary tract infection (UTI) after renal transplantation,so as to provide a theoretical basis of reducing the rate of postoperative UTI effectively.Method Such databases as CNKI,VIP,Wanfang,Pubmed,Embase,Ovid,and EBSCO were searched from January 1995 to December 2015 for collecting the studies about UTI after renal transplantation.The search keywords were renal transplantation,kidney transplantation,urinary tract infection and risk factors.Meta-analysis was performed by using the RevMan 5.2 software.Result Fifteen studies were identified,including 1 236 patients in UTI group and 2 729 patients in the control group (non UTI group).The two groups had no significant differences in recipient age,diabetes mellitus history,peritoneal dialysis,cytomegaovirus infection,acute rejection,usage of MMF,usage of Tacrolimus,usage of CsA and retransplantation.The incidence of UTI after renal transplantation was significantly higher in female patients than male patients (OR:2.69;95% CI:1.92-3.77;P<0.000 01).The incidence of UTI of cadaveric renal transplantation was higher than living donor renal transplantation (OR:1.51;95% CI:1.71-1.95;P=0.002).Using D-J tube for urinary reconstruction significantly increased the incidence of UTI (OR:1.51;95 % CI:1.07-2.13;P =0.02).Patients in the UTI group had a significantly longer preoperative dialysis time (WMD:1.48;95% CI:0.22-2.74;P =0.02).Conclusion The female recipients,cadaveric renal transplantation,using D-J tube and prolonged preoperative dialysis time were factors affecting the risk of UTI.UTI after renal transplantation had no relationship with recipient age,diabetes mellitus history,peritoneal dialysis,cytomegaovirus infection,acute rejection,usage of MMF,Tacrolimus and CsA,and retransplantation.

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