FXR agonist GW4064 ameliorates tacrolimus-induced abnormalities in glucose metabolism / 中国临床药理学与治疗学

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.

Clinical retrospective analysis in delayed graft function morbidity of kidney transplantation recipients and gender factors in both donors and recipients / 中华器官移植杂志

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 .

Mild hypothermia pretreatment attenuates liver L02 cells hypoxic-ischemia reperfusion injury through inhibiting JNK activation / 中华器官移植杂志

Objective To investigate the protective effects and the possible mechanisms of mild hypothermia against liver L02 cells hypoxic-ischernia reperfusion injury by using mild hypothermia pretreatment.Methods L02 cells were randomly divided into three groups:normal control group (N group),hypoxic-ischemia reperfusion group (control group) and hypoxic-ischemia reperfusion with mild hypothermia pretreatment group (experimental group).Before hypoxic-ischemia reperfusion,cells in experimental group were pretreated with mild hypothermia for 6 h,while the other groups were given the normal culture.Thereafter,the hypoxic-ischemia reperfusion models of L02 cells were performed by a tri-gas incubator to hypoxic-ischemia culture for 12 h,followed by reperfusion with normal conditions for 4 hours.Cells in N group were cultured in normal conditions.The temperature of experimental groups was set to 32 C.The samples were collected,and the cell injury,the cell vitality,the cell apoptosis and the expression of JNK in different groups were detected.Results Compared to N group,the levels of alanine aminotransferase (ALT),aspartate transaminase (AST) and lactic dehydrogenase (LDH) were significantly increased,the cell vitality was significantly decreased,the cell apoptosis and the expression of p-JNK were significantly increased in control and experimental groups (P ＜ 0.05).Compared to control group,all these changes were significantly ameliorated in experimental group.The levels of ALT,AST and LDH in control group were (30.0 ± 4.6),(26.3 ± 3.8) and (1129.0 ± 134.3) U/L,and those in the experimental group were (21.0 ± 2.7),(18.7 ± 2.1)and (898.3 ± 79.2),respectively.The cell vitality in control group and experimental group was (64.33 ± 2.32)％ and (78.17± 3.01)％ respectively.The cell apoptosis in control group and experimental group was (32.4 ± 2.3) ％ and (18.8 ± 1.4) ％ respectively.The expression of p-JNK in experimental group was significantly decreased.All these differences were statistically significant (P＜0.05).Conclusion Mild hypothermia pretreatment could significantly attenuate liver L02 cells hypoxicischemia reperfusion injury probably by inhibiting JNK activation.

Mild hypothermia pretreatment attenuates liver L02 cells hypoxic-ischemia reperfusion injury through inhibiting JNK activation / 中华器官移植杂志

Objective To investigate the protective effects and the possible mechanisms of mild hypothermia against liver L02 cells hypoxic-ischernia reperfusion injury by using mild hypothermia pretreatment.Methods L02 cells were randomly divided into three groups:normal control group (N group),hypoxic-ischemia reperfusion group (control group) and hypoxic-ischemia reperfusion with mild hypothermia pretreatment group (experimental group).Before hypoxic-ischemia reperfusion,cells in experimental group were pretreated with mild hypothermia for 6 h,while the other groups were given the normal culture.Thereafter,the hypoxic-ischemia reperfusion models of L02 cells were performed by a tri-gas incubator to hypoxic-ischemia culture for 12 h,followed by reperfusion with normal conditions for 4 hours.Cells in N group were cultured in normal conditions.The temperature of experimental groups was set to 32 C.The samples were collected,and the cell injury,the cell vitality,the cell apoptosis and the expression of JNK in different groups were detected.Results Compared to N group,the levels of alanine aminotransferase (ALT),aspartate transaminase (AST) and lactic dehydrogenase (LDH) were significantly increased,the cell vitality was significantly decreased,the cell apoptosis and the expression of p-JNK were significantly increased in control and experimental groups (P ＜ 0.05).Compared to control group,all these changes were significantly ameliorated in experimental group.The levels of ALT,AST and LDH in control group were (30.0 ± 4.6),(26.3 ± 3.8) and (1129.0 ± 134.3) U/L,and those in the experimental group were (21.0 ± 2.7),(18.7 ± 2.1)and (898.3 ± 79.2),respectively.The cell vitality in control group and experimental group was (64.33 ± 2.32)％ and (78.17± 3.01)％ respectively.The cell apoptosis in control group and experimental group was (32.4 ± 2.3) ％ and (18.8 ± 1.4) ％ respectively.The expression of p-JNK in experimental group was significantly decreased.All these differences were statistically significant (P＜0.05).Conclusion Mild hypothermia pretreatment could significantly attenuate liver L02 cells hypoxicischemia reperfusion injury probably by inhibiting JNK activation.

Meta-analysis of the risk factors of urinary tract infection after renal transplantation / 中华器官移植杂志

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.

Research advance of preoperative assessment in patients with auto liver transplantation / 中华肝胆外科杂志

Auto liver transplantation (ALT) is a treatment option for patients with liver space-occupying lesion that could not be removed by conventional surgery and severe liver trauma,which also helps alleviate the shortage of donor liver.But many problems like the preoperative assessment,the tolerance of patients to surgery and anesthesia,delayed postoperative recovery of the liver function,primary non-function,liver failure and hepatic encephalopathy and even death still need to be addressed.Thus,it is particularly important to evaluate the operative indication,completely and accurately assess the preoperative liver function and liver function reserve,and reduce the perioperative mortality and complication in order to improve the prognosis of ALT.Combined with literalure and the experience in our center,this paper summarized the research advance of preoperative assessment in patients with ALT.

Moderate hypothermia reduces hepatic ischemia-reperfusion injury / 中华肝胆外科杂志

Objective To explore the effect of moderate hypothermia (MH) in liver ischemiareperfusion (IR) injury.Methods Male BALB/c mice (8 weeks old,n =15) were randomly divided into three groups:IR group:five mice subjected to 70％ hepatic IR (hepatic vascular triad above the bifurcation occlusion for 35 min before 24 h reperfusion) in normal temperature condition (37 ±0.5 ℃);MH + IR group:five mice were treated with MH (32 ±0.5 ℃) for 2 h before 70％ hepatic IR was performed;sham group:the other five mice were subjected to laparotomy and liver manipulations without vascular occlusion.AST and ALT in plasma were detected in all mice,and the morphological changes,cell apoptosis and the cold-inducible RNA-binding protein (CIRP) expression after MH in liver tissues were detected.Results Compared with IR group,the ALT and AST levels in MH + IR group were significantly decreased.In IR group,the liver morphology deteriorated with more severe hydropic degeneration and more cell apoptosis.In MH + IR group,the expression of CIRP began to increase after MH preconditioning.Conclusion MH preconditioning could protect against the liver ischemia-reperfusion injury.

Isolation and identification of pathogenic bacterium which caused hemorrhagic diarrhea in newborn swine / 中国人兽共患病学报

The Escherichia coli (E.coli) strain from intestinal tract of died newborn swine was isolated and cultured.Preliminary identification of the isolated strain was conducted by conventional biochemical tests,and the molecular biology detections of toxicity gene and typing gene were completed by multi-PCR.Stable toxin and heat-labile enterotoxin genes of E.coli were detected from the isolated strain.By amplifying and sequencing bacterial 16s rDNA and fliC gene,the isolated strain was identified as H10 by Blast analysis.The homology of strain H10 was 99% with bacterial 16s rDNA gene and 98% with fliC gene.

IL-18 augments protective immunity of Sj23 plasmid DNA vaccine against Schistosoma japonicum in mice / 中国兽医学报

Two recombinant plasmids pVAX/Sj23 and pVAX/mIL-18 containing Schistosoma japonicum 23 000 membrane protein (Sj23) and murine IL-18 were evaluated for their ability to induce immune responses and to protect against S. japonicum challenge in mice. All animals vaccinated with pVAX/Sj23 alone or plus pVAX/mIL-18 developed specific anti-SWAP (soluble worm antigen preparation) ELISA antibody and splenocyte proliferation response,and co-injection of pVAX/mIL-18 significantly increased the production of IFN-γ and IL-2 compared with pVAX/Sj23 alone, indicating that IL-18 enhances the Th1-dominant immune response. The challenge experiment showed that worm reduction rates in pVAX/Sj23 group compared with control group (pVAX1) was 26.5% and in the pVAX/Sj23 plus pVAX/mIL-18 group was 41.9% ,and the hepatic egg reduction rates were 42.7 and 49.6%,respectively. These results indicated that co-injection of an IL-18 plasmid with Sj23 DNA vaccine efficiently improves the protective effect against S. japonicum infection.

Toxic effect of oral ricin on the mouse intestinal tract and immune organs / 中国兽医学报

The experiment aimed to study the toxic effect of oral ricin on gastrointestinal tract and immune organs of mice with the dose of 1/5 LD50.In early days of intoxication,there was an obviously decrease in daffy weight and relative weight of thymus and spleen,fllowing the excretion of toxin,they had a trend of recovering to the normal state.Also,results of pathological section,scanning electron microscope and transmission electron microscope showed that ricin would induce a series of pathological reaction in intestines,meanwhile,the splenocytes displayed significant symptom of apoptosis and necrosis.