BACKGROUND: Documents recorded that the correlation between micro emulsion Ciclosporin peak concentration (C_2) and area under curve was best with maximum individual difference. According to C_2, dose of Ciclosporin can be adjusted indMdually to decrease acute rejection and Ciclosporin toxicity, which has widely used in perioperative stage of renal transplanted recipients. However, some transplantation center still used tough concentration (C_0) to adjust the dose of Ciclosporin in stable stage of renal transplanted recipients. OBJECTIVE: To analyze the efficacy and safety of changing from monitoring C_0 to C_2 in stable stage recipients following renal transplantation. METHODS: Totally 65 patients with renal transplantation were enrolled in this study, including 31 males and 34 females, aged 20-57 (39.4±15.3) years. Within 3 months prior to this study, all patients did not suffered from rejection, and their serum creatinine and urea nitrogen were stable (creatinine ≤180 μmol/L). They were in stable stage after renal transplantation. Their period of transplantation and function of allograft were recorded. Their C_0 and C_2 of Ciclosporin were assayed. According to the target C_2 value 500-600 μg/L, the patients were prospectively and randomly divided into 3 groups. In the high C_2 group (n=17), the dose of Ciclosporin was decreased. In the target C_2 group (n=23), the dose of Ciclosporin was remained. In the low C_2 group (n=25), the dose of Ciclosporin was increased. All of the patients were followed-up for 12 months. The grafts function and the complications of heart, lung and brain were compared. RESULTS AND CONCLUSION: According to the target concentration of Ciclosporin C_2, the dose of Ciclosporin in the high C_2 group was decreased by 575.0 mg. The Creatinine and urea nitrogen of 88% patients were stable, while blood pressure, blood fat and blood uric acid decreased in parts of patients. In the target C_2 group, the levels of creatinine, urea nitrogen, Co and C_2 of patients were stable, no complications of heart, lung and brain occurred. According to the target concentration of Ciclosporin C_2, the dose of Ciclosporin in low C_2 group was increased by 755.0 mg. The creatinine and urea nitrogen of 84% patients were stable. All of the patients were no complications of heart, lung and brain. It is safe and effective to adjust Ciclospori dose under C_2 monitoring according to the target peak concentration (500-600 μg/L) in most stable stage recipients following renal transplantation.

Objective To investigate the clinical features of bilateral native pelvic and ureteral transitional cell carcinoma (TCC) in renal transplant patients. Methods A retrospective analysis was carried out on 16 patients with bilateral native pelvic and ureteral TCC after kidney transplantation.The mean time between transplantation and diagnosis of upper urinary TCC was 56. 2 ± 33. 0 months.Two patients were suffered from bilateral upper urinary TCC at the same time. The mean interval between 2 upper urinary tract operations of the remaining 14 cases was 8. 6 ± 6. 7 months. Hematuria and hydronephrosis of native kidneys were the main symptoms and targets in checkup. Intravesical chemotherapy was postoperatively given. Results All operations were performed successfully. All specimens obtained from the operations were pathologically diagnosed as TCC. The TCC location involved pure native pelvis (n = 4), pure native ureter (n = 9), and pelvis combined with ureter (n = 19). Pelvic TCC pathological grades included grade 1 in 8 cases, grade 2 in 11 cases, and grade 3 in 4 cases; Ureteral TCC grades included grade 1 in 6 cases, grade 2 in 10 cases, and grade 3 in 12 cases.Patients were followed up for 26. 8 ± 25. 1 months. One patient died of lung metastasis. (One case of lumbar soft tissue transfer was given local excision. The remaining patients had no recurrence and metastasis. Conclusion Renal transplant patients with hematuria and native renal hydronephrosis should be highly vigilant of the occurrence of upper urinary tract TCC. TCC after renal transplantation is invasive. Prophylactic contralateral nephroureterectomy should be performed on the recipients having TCC at the bladder and one side of native upper urinary tract.

Background: Hepatocyte nuclear factor 4α (HNF4α) plays an important role in the development of liver,and studies demonstrate that it is correlated with the pathogenesis of hepatocellular carcinoma (HCC).However,the regulatory effect of HNF4α on expression of vascular endothelial growth factor (VEGF) in human HCC cell lines and tube formation of human umbilical vein endothelial cell (HUVEC) is not yet clear.Aims: To investigate the effect of HNF4α on expression of VEGF in human HCC cell lines and tube formation of HUVEC.Methods: Lentiviral vector overexpressed HNF4α was constructed,and then transfected into HepG2 and SMMC-7721 cells (experimental group),cells transfected with lentiviral blank vector and cells without transfection were served as negative control group and blank control group,respectively.The mRNA and protein expressions of HNF4α,VEGF were detected by qRT-PCR and Western blotting,respectively.The conditioned media of HepG2 and SMMC-7721 cells were co-cultured with HUVEC,and number of HUVEC tube formation was measured.Results: HepG2 and SMMC-7721 cells with stable overexpression of HNF4α were successfully established.Compared with negative control group and blank control group,mRNA and protein expressions of VEGF in experimental group were significantly decreased (P＜0.05),and number of HUVEC tube formation was significantly decreased (P＜0.05).Conclusions: HNF4α can significantly inhibit the expression of VEGF in HepG2 and SMMC-7721 cells and tube formation of HUVEC.

Objective To unravel the relationship between Toll-like receptor 4 (TLR4) expression in platelets and the activation of platelet in thrombocytopenia (TCP) in case of sepsis. Method A total of 64 patients with sepsis were prospectively studied with control. Platelet count (PC), mean platelet volume (MPV),platelet distribution width (PDW),platelet TLR4 expression, platelet PAC-1 expression, sCD40L and TNF-α concentrations were compared between healthy control group (15 cases) and sepsis group on admission and 3 d,Sd,and 9 days after admission. The changes of MPV and PDW in TCP and non-TCP subgroups of sepsis before and after treatment were recorded. Prognostic index was analyzed. Results The PC was lower in sepsis group (P=0.006), and MPV and PDW were higher in sepsis group than those in healthy control group (P = 0.046, P =0.001). Platelet TLR4 and PAC-1 expressions, and sCD40L and TNF-α levels also increased more significantly in sepsis group (P ＜ 0.001). PAC-1 expression and TNF- level were higher in TCP group than those in non-TCP group before and after treatment (P = 0.023, P = 0.011). The sCD40L concentration and platelet TLR4 expression were significantly higher in treated TCP groups than in non-TCP group (P = 0.047, P = 0.001). Compared with non-TCP,the rate of bleeding was higher (P = 0.024) and the length of ICU stay was longer (P = 0.013).The APACHE Ⅱ score and the 28-day mortality were higher in TCP group (P ＜ 0.01, P = 0.048). Conclusions The elevation of platelet TLR4 expression in sepsis along with platelet activation is closely related to the incidence of thrombocytopenia. The occurrence of TCP is a poor prognosis sign of sepsis.

Objective To investigate the effects of cyclosporine on cell proliferation, apoptosis and angiogenesis of bladder cancer in rats induced with BBN.Methods Ten samples of SD rats bladder cancer induced with BBN and cyclosporine simultaneously and 10 samples of SD rats bladder cancer induced with BBN only as control were used to observe the effects of cyclosporine on cell proliferation, apoptosis and angiogenesis of bladder cancer in rats.Immunohistochemistry stain with PCNA, TUNEL and immunohistochemistry stain with CD31 were used to analyze cell proliferation,apoptosis and angiogenesis of bladder cancer in rats respectively. Results The differences of proliferation index (35.3±8.6)% and (28. 7±8.0)% respectively (P＜0.05), apoptotic index (2. 5±0.8)% and (4.3±1.3)% respectively (P＜0.05) and microvessel density 32.5±8.2 and 26.3±8.1 respectively (P＜0.05) between experimental group and control group were all significant.Conclusions Cyclosporine may stimulate the growth and development of bladder cancer through mechanisms of cell proliferation, apoptosis and angiogenesis.

OBJECTIVE: Panel reactive antibody (PRA) can induce acute rejection following kidney transplantation, however, it is poorly understood which PRA is more associated with rejection. Therefore, the aim of this study is to analyze the correlation between PRA and rejection by observing the change of PRA Ⅰ and PRA Ⅱ prior to and after the kidney transplantation. METHODS: Levels of PRA Ⅰ and PRA Ⅱ were observed in 100 patients received kidney transplantation at the Department of Urology, Beijing Chaoyang Hospital Affiliated to the Capital Medical University. During these 100 patients, 18 patients had PRA changes after operation. The relationship between PRA changes after kidney transplantation and acute rejection were analyzed. RESULTS: Totally 18 patients were included in the final analysis. Nine of them occurred acute rejection with obviously increased PRA Ⅱ (P=0.040), however, the PRA Ⅰ had no significant changes (P=0.707). The changes of PRA Ⅰ and PRA Ⅱ had no significance in the remaining 9 patients prior to and after kidney transplantation. The overall level of PRA increased in 7 patients, in 5 patients with increased PRA Ⅱ, 4 patients suffered acute rejection, 1 of which was renal allogreft failure; 2 cases with PRA Ⅰ increasing did not occur acute rejection. The overall level of PRA declined in 11 patients, including 5 patients with PRA Ⅱ decreased, 1 patient occurred acute rejection; 4 patients in 6 patients with PRA Ⅰ declined suffered acute rejection. CONCLUSIONS: The increased PRA Ⅱ after transplantation easily result in acute rejection, which has definite correlation to acute rejection, however, the PRA Ⅰ changes has no impact on acute rejection.

Objective To evaluate the effects of 131 adrenoceptor anfisense on blood pressure and?1 adrenoceptor mRNA and protein levels in 2 kidney 1 clip(2K1C)rats.Method 2KIC hypertensive rots were produced by clipping renal artery of SD rats.Liposome/AS-ODNs 2.0 were tested intravenously in rats with 2KIC hypertension.Animals were divided into 5 groups(n=18 in each group):?1-AS-ODN group,?1-IN-ODN group,2K1C group,Sham group and SD group.Blood pressure was measured by tail-cuff method,the levels of myocardial?adreneceptor mRNA and protein were tested by RT-PCR and binding assay.Results On the basis of the magnitude and duration of hypotension,?1-AS-ODN decreased blood pressure by 39 mmHg at the most for 4 weeks.Compared with the 2KIC group,?1-AS-ODN did not significantly change the levels of myocardial?1 adrenoceptor mRNA but significantly decreased the levels of myocardial?1 adrenoceptor protein at 2,7,30 days (P

OBJECTIVE To investigate the transgenerational effects of a hypothala mic-pituitary-ad-renal (HPA)axis -associated neuroendocrine metabolic progra mming alteration fro m F1 to adult second generation (F2)with prenatal ethanol ingestion.METHODS Pregnant Wistar rats were ad ministered with ethanol (4 mg·kg -1·d -1 )fro m gestational day 1 1 until delivery.F1 rats were fed a high-fat diet fro m postnatal week 4 (PW4)and were cross-mated in PW 16 -20.F2 rats were fed a standard diet fro m PW4 and rectal te mperature was measured in PW20,oral glucose tolerance test (OGTT)was con-ducted in PW21 ,blood sa mples and hypothala mus were collected in PW24 to investigate seru m lipids and HPA axis activity.RESULTS Co mparing to the F2 control group ,rectal te mperature in F2 ethanol group were higher (P<0.01 ),sugar tolerance in F2 male group was i mpaired (P<0.05),seru m corti-costerone and hypothala mus arginine vasopressin (AVP) mRNA were increased (P <0.05);seru m insulin were decreased (P<0.05)and male rats showed i mpaired glucose tolerance (P<0.05);seru m high-density lipoproteincholesterol (HDL-C)decrease (P <0.05)and total cholesterol (TCH)/HDL-C and low density lipoproteincholesterol (LDL-C)/HDL-C ratios were markedly increased (P <0.05,P <0.01 ).CONCLUSION Prenatal ethanol exposure induced metabolic syndro me has transgenerational effects,which may originate fro m the intrauterine progra mming of altered HPA axis-associated neuroen-docrine metabolis m.

AIM: To study the effect of focal adhesion kinase (FAK) phosphorylation on the adhesion and migration of smooth muscle cells (SMCs) stimulated by fibronectin (FN). METHODS: Cultured SMCs were stimulated by different concentrations of FN.FAK expression and phosphorylation were detected by immunoprecipitation and Western blot. To investigate the modulating effect of FAK on tyrosine phosphorylation and SMCs adhesion and migration, FAK antisense oligodeoxynucleotides (ODNs) were transfected into SMCs by actionic lipid method. RESULTS: FAK expression increased when SMCs adhesion and migration were induced by FN at different concentrations used in the experiment. However, FAK phosphorylation was only observed by FN stimulation at concentration of 20 mg/L. FAK antisense ODNs inhibited FAK phosphorylation magnificently. The migration rates of SMCs were reduced by 17.89%-27.67% when FN was used at concentration from 5 mg/L to 60 mg/L. The decreased migrating cell numbers were showed the same patterns. The apoptotic SMCs were 33.57% higher than that control ( P

Background and purpose:Although bortezomib has become one of the major therapeutic agents against newly diagnosed or relapsed multiple myeloma (MM), there are some patients who become resistant to bor-tezomib and then relapse, emerging as a major obstacle to long-term survival of MM patients. It has been found that elevation of intracellular cyclic adenosine monophosphate (cAMP) levels could induce cell cycle arrest and apoptosis in MM cells,which has become an interesting approach to MM therapy. This study aimed to investigate possible effects of forskolin combined with bortezomib on bortezomib-resistant myeloma cells and further explore its mechanisms. Methods:The bortezomib-resistant MM cell lines H929-R and primary cells from patients who do not respond to bortezomib were used asin vitro models. The inlfuences of bortezomib and/or forskolin on MM cells were evaluated through cellular morphology, changes of cell distribution and apoptotic rate. Meanwhile, lfow cytometry analysis was used to detect mitochondrial transmembrane potential (ΔΨm) and the expression levels of apoptosis regulators in these cells before and after the treatment were detected by Western blot.Results:Bortezomib (20 nmol/L) synergized with forskolin (50nmol/L) to induce apoptosis of H929-R cells and bortezomib-resistant primary cells. In addition, borte-zomib synergized with forskolin to induce collapse of mitochondrial transmembrane and facilitate the degradation of anti-apoptosis proteins including Bcl-2 and Mcl-1.Conclusion:Bortezomib could synergize with forskolin to induce apoptosis in bortezomib-resistant MM cells.