Cysteine protease inhibitor SN (CST1) is one of the members of type 2 Cystatin superfamily. It is widely expressed and distributed in mammals. It contains many types of CST proteins and is located on chromosome 20p11.2. Cystatin SN has a variety of biological functions and is involved in the occurrence and development of tumor genesis and metastasis, inflammation, cell cycle and aging.

Objective To evaluate the efficacy and safety of single bolus high dose (SD group) ATG-Fresenius induction therapy in kidney transplantation vs.multiple low dose (MD group) administration.Methods A multiple center,prospective,randomized and controlled clinical study was performed on 280 de novo renal transplant recipients from 19 centers.Patients were randomized into 2 groups as follows:SD group,a single high dose (7-9 mg/kg) of ATG-F infused as an induction agent before the vessel anastomoses;MD group,2 mg/kg of ATG-F daily administrated in postoperative 4 days.All the patients accepted maintenance immunosuppressive protocol including tacrolimus,mycophenolate and prednisone.Patients were assessed and data were collected at regular schedule clinic visits on the day 1,3,7,14,30,90,180,270 and 365.The primary end point of efficacy was therapeutic failure rate [the number of death,grafts loss and acute rejection (AR)].The event first occurred should be used in the classification of patients.The non-inferiority evaluation of the two treatment regimens was done based on treatment failure rate.The secondary end points of efficacy were the incidence of AR,delayed graft function (DGF),1-year survival rate of patients and grafts,and serum creatinine at each visiting point.The indicators for safety evaluation included hemotologic variation and incidence of adverse events.Results The therapeutic failure rate in SD group was non-inferior to the MD group (17.24％ vs.23.08％).AR was the major cause of therapeutic failure and there was similar incidence of AR between SD gronp and MD group (12.07％ vs.21.37％).There was no significant difference in the incidence of DGF between SD group and MD group (12.07％ vs.6.84％,P =0.1721).The 1-year patient's survival rate and 1-year graft survival rate in SD group and MD group showed no significant difference (96.55％ vs.98.29％,P =0.6714;94.83％ vs 98.29％,P =0.2750).The serum creatinine level showed no significant differences between two groups at each visit point.There was also no significant difference in total incidence of adverse events between the two groups.In addition,there was also no statistically significant difference in the incidence of concerned and drug-related adverse events between the two groups,including infection,hemotologic abnormality,liver or renal dysfunction,gastrointestinal disorder,etc.After ATG--F administration,peripheral blood lymphocytes in the SD and the MD group immediately decreased but nearly restored to the normal level on the postoperative day 30 and 90 respectively.No severe granulocytopenia,erythropenia or thrombocytopenia occurred in both two groups.Conclusion The efficacy and safety of single high dose of ATG-F induction are non-inferior to multiple low dose ATG-F induction,moreover,single high dose of ATG-F induction is administered more conveniently and economically.

Objective To evaluate the effect of conversion from mycophenolic acid (MPA) to mizoribine (MZR) in renal transplant recipients with gastrointestinal tract (GI) symptoms.Methods A total of 355 renal transplant recipients with GI symptoms caused by MPA administration were enrolled from April 2015 to March 2017 in 25 different renal transplant centers in China.The symptomatic improvement of GI before (baseline) and after conversion to MZR (1,2,4 weeks) was assessed by each item of GI symptoms indication.In addition,the efficacy and safety of the conversion therapy during 12 months were determined.Results Patients showed improvement in GI symptoms including diarrhea,abdominal pain,abdominal distention and stomachache after conversion to MZR 1,2,4 weeks (P＜0.05).In patients with different severity of diarrhea,conversion to MZR therapy significantly improved diarrhea (P＜0.05).During 12 months,no patient experienced clinical immune rejection.We did not observe any infections,leucopenia and other serious side effects.Conclusion MZR could markedly improve GI symptoms caused by MPA administration in renal transplant recipients.

Objective To study the expression of interleukin (IL-17A) in primary liver cancer (PHC) tissue and its clinical significance.Methods Reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry was performed respectively to detect the expression of IL-17A mRNA and CD34 in tumor tissues from 37 patients with PHC.Murine H22 cells cultured in vitro were exposed to IL-17A at different dosages (0.1,0.5,1.0,5.0,10,50,100,500,1000 ng/ml) and the cell proliferation was assayed by MTT.IL-17A was administered to the mice transplanted with H22 cancer cells via caudal vein and the tumor volume was measured by vernier caliper.Immunohistochemistry was used to detect the CD31 expression in H22 cancer tissues.Results IL-17A mRNA was detected in 26 of the 37 samples of primary liver cancer.The microvessel densities in IL-17A-positive samples and IL-17A-negative samples were 66.6 ± 2.5 and 26.7--2.5,respectively.The difference between two groups was significant (P＜0.01).The proliferation of H22 cells exposed to various dosages of IL-17A was not different (P＞0.05).The volume of murine tumor tissue in animals treated with IL-17A was (843.6± 90.9) mm3 and in untreated animals was (198.7±24.4) mm3 (P＜0.01).The microvessel density in treated group and control group was 71.9± 6.8 and 33.3 ± 2.9,respectively (P＜0.01).Conclusions The expression of IL-17A could be detected in a considerable proportion of primary liver cancers and correlated with angiogenesis.Exogenous IL-17A could not accelerate H22 cell proliferation in vitro but in vivo probably via enhancing angiogenesis.

Objective To investigate the impact of CD4+ CD25+ FOXP3+ regulatory T(Treg) cells on tumor recurrence in liver transplantation for hepatocellular carcinoma (HCC). Methods Im-munohistochemistry and flow cytometry were used for analysis of the frequency of Treg. Meanwhile,it was compared with that of non-cancer liver transplantation patients. Results The frequency of CD4+CD25+ FOXP3+ regulatory T cells in the blood of HCC liver transplantation was (10. 15 ±1. 00) % , which was significantly higher than that in the normal control group (3. 20±1. 18) %. Cir-culating CD4+ CD25+ FOXP3+ Treg frequency was increased significantly and correlated with the tumor recurrence in the HCC patients. An abundant accumulation of Treg concurrent with significant-ly reduced infiltration of CD8+T cells was found in tumor regions. Conclusion Increased CD4+ D25+FoxP3+ Treg may impair the effectors function of CD8+ T cells, promote the tumor recurrence and re-present a therapeutic target for HCC liver transplantation.