AIM:To observe the effect of micronised fenofibrate(lipanthyl)on lipotoxicity and insulin sensitivity(IS)in spontaneously hypertensive rats(SHR)with high-fat diet.METHODS:Twenty-seven SHR were randomly divided into three groups:normal chow group(n=9),high-fat diet group(n=9)and micronised fenofibrate treatment group(n=9).Micronised fenofibrate 100 mg?kg-1?d-1 was given orally to SHR,which diet on high-fat diet for three months.Intramuscular lipids were observed and lipids accumulation index(LAI)was calculated.Nonesterified fatty acid,glucose and insulin were determined in all rats.RESULTS:(1)Compared to SHR in normal chow diet group,body weight and the level of serum TG and TC increased significantly and the level of HDL-C decreased significantly in SHR fed with high-fat diet(P

AIM:To investigate the effect of activation of retinoid X receptor (RXR) on transforming growth factor β1 (TGF-β1) induced collagen synthesis under hypoxic environment in rat cardiac fibroblasts (CFs) and underlying molecular mechanisms .METHODS: CFs were cultured using myocardial tissue with dry method .Hypoxic environment was established for CFs by continuous nitrogen supplement .Type I and type III collagens in supernatants were detected by ELISA.Nuclear and cytoplasmic extractions were prepared using NE-PER nuclear and cytoplasmic extraction reagents .The protein levels of Smad2 and p-Smad2 were determined by Western blot and immunocytochemical staining .RESULTS:Un-der hypoxic condition , TGF-β1 (0.01~10 μg/L) increased the synthesis of type I and type III collagens in a dose-de-pendent manner in the CFs .At the concentration of 5μg/L, the synthesis of collagen I and III was significantly increased as compared with control group (P<0.01).RXR agonist 9-cis-retinoic acid (9-cis-RA;10 -9 ~10 -6 mol/L) decreased TGF-β1 (5μg/L)-induced synthesis of type I and III collagens in a dose-dependent manner in the CFs under hypoxic con-dition.The synthesis of type I and type III collagens was significantly inhibited by 9-cis-RA (P<0.01).Smad2 inhibitor ( 20 nmol/L) showed similar inhibitory effect on the synthesis of type I and III collagens induced by TGF -β1 under hypoxic condition.Compared with TGF-β1 intervention group, the cytoplasmic level of p-Smad2 in the CFs was significantly in-creased in TGF-β1+9-cis-RA group, but the nuclear p-Smad2 level was significantly decreased (P<0.05).CONCLU-SION:Retinoid X receptor agonist 9-cis-RA inhibits TGF-β1-induced synthesis of type I and type III collagens in the CFs by repressing p-Smad2 nuclear translocation under hypoxic condition .

Granulocyte colony-stimulating factor (G-CSF) has been demonstrated to have neuroprotective effects in rat model with focal cerebral ischemia through anti-apoptotic pathways and by promoting proliferation of neural stem cells. In the present study, we examined the neuroprotective effect of G-CSF in an acute focal cerebral ischemia rat model with lipid metabolism disorder. Eighty male SD rats were randomly divided into normal diet control group (NC group) and high-fat diet group (HFD group) (n = 40 in each). In HFD group, rats were fed on high fat diet to induce atherosclerosis. After 29 days, 4 rats from each group were sacrificed to evaluate the effects of different diets, and the middle cerebral artery occlusion (MCAO) was performed in the rest of the rats. MCAO rats received either G-CSF (50 μg·kg(-1)·mL(-1)) or phosphate buffered saline (PBS) injection through the external jugular vein for 5 days, which was followed by 5-bromo-deoxy uridine (BrdU, i.p., 50 mg/kg) injection for another 7 days. To evaluate the effects of G-CSF treatment on neurological function, the modified neurological severity score (mNSS) was calculated. The vascular distribution, ischemic cells proliferation, cell apoptosis and the expression of vascular endothelial growth factor (VEGF) were measured to determine the effects of G-CSF treatment. Our results showed that G-CSF-treated rats had a lower mNSS than PBS-treated rats in both NC group and HFD group. G-CSF injection promoted endothelial cell proliferation and vascular regeneration, and inhibited cell apoptosis. The serum and tissue levels of VEGF were significantly increased after G-CSF treatment. It is concluded that G-CSF exerts its neuroprotective effect in focal cerebral ischemia rats with hyperlipidemia by enhancing angiogenesis, promoting cells proliferation, decreasing cell apoptosis, and increasing local VEGF expression.

Objective To evaluate the relevant causes of neurologic complications following liver transplantation.Methods 155 adult patients (131 males, 24 females) who received liver transplantation for the first time at Tongji Hospital between January 2005 and September 2009 were identified.Case notes were reviewed and demographic data, details of the liver disease, neurologic complications, MELD score and discharge information were recorded.Results Neurologic complications occurred following 36 transplants (23.2 %), The complications included mental symptoms in 15 cases (41.7 %), disorder of consciousness and action in 9 cases (25 %), and coma in 12 cases (33.3 %).Twelve percent patients with liver cancer experienced a neurologic complication, which was lower than for other transplant indications, like acute and chronic hepatic failure because of HBV infection (33.3 %, P＜0.01), inborn/metabolic disease (40 %, P＜0.05), and HCV Infection (25 %, P = 0.36).Patients who experienced a neurologic problem had significantly higher MELD score (for non-cancer patients:22.93 ± 8.21; for cancer patients:17 ± 5.4) than the other Patients (for non-cancer patients:18.33 + 8.47, P＜0.05; for cancer patients:13 ±3.4, P＜0.01).The rate of infection (36.1 %) and mortality (30.5 %) were significantly higher in patients with neurologic complications (P＜0.01).The levels of ALT, TBil, ALB, PT and the concentrations of serum sodium and chlorine had no impact on neurologic complications.Conclusion Neurologic complications are common in liver transplant recipients.These complications are related to primary disease and liver function before the operation, and increase the rate of infection and mortality.

AIM:To explore the effects of atorvastatin (Atorv) on atherosclerosis in streptozotocin (STZ)-in-duced diabetic apolipoprotein E knockout ( ApoE-/-) mice with fat-rich diet and the possible mechanism .METHODS:C57 mice served as control.ApoE-/-mice (n=34) fed with high-fat diet were randomly divided into ApoE-/-group, STZ-ApoE-/-group and STZ-ApoE-/-+Atorv group.Intraperitoneal injection of streptozotocin was performed to create di-abetic animal model .Blood glucose was determined by glucose oxidase method .Blood lipid levels were detected by enzymic method or selective homogeneous method .The plaque area in the thoracic aorta was measured by HE staining .The protein level of nicotinamide-adenine dinucleotide phosphate ( NADPH) oxidase subunit gp91phox in the thoracic aorta was deter-mined by Western blotting .The levels of reactive oxygen species ( ROS) in blood and thoracic aorta homogenates were de-tected by Fenton reaction and Griess reagent .Human umbilical vein endothelial cells ( HUVECs ) were isolated from healthy umbilical cords by collagenase I and cultured .ROS production was detected by flow cytometry .NADPH oxidase ac-tivity was measured using lucigenin assay .Effects of retinoid X receptor α( RXRα) on inhibition of oxidative stress by ator-vastatin were evaluated by RNA interference and plasmid transfection .RESULTS: (1) Compared with C57 group, the plaque areas of the thoracic aorta in ApoE-/-group were increased .No difference of the fasting glucose between the 2 groups was observed.The levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), thoracic aorta gp91phox protein and ROS in blood and thoracic aorta homogenates were higher in ApoE-/-group than those in C57 group.(2) Compared with ApoE-/-group, the plaque areas of the thoracic aorta in STZ-ApoE-/-group were further enlarged [(314.13 ±35.72) μm2 vs (215.88 ±34.19) μm2, P<0.05].The levels of blood glucose, TG, TC and LDL-C, thoracic aorta gp91phox protein and ROS in blood and thoracic aorta homogenates were higher in STZ-ApoE-/-group than those in ApoE-/-group (P<0.05).(3) Compared with STZ-ApoE-/-group, the plaque areas of the thoracic aorta in STZ-ApoE-/-+Atorv group were reduced [(217.47 ±24.56) μm2 vs (314.13 ±35.72) μm2, P<0.05].The levels of blood glucose , LDL-C, TC, HDL-C and TG showed no significant difference between the 2 groups.Thoracic aorta gp91phox protein level and ROS production in blood and thoracic aorta homogenates were lower in STZ -ApoE-/-+Atorv group than those in STZ-ApoE-/-group (P<0.05).(4) High glucose-induced increases in NADPH oxidase activity and gp91phox expression were significantly inhibited by atorvastatin (10-6 mol/L) in HUVECs.The inhibitory effects of atorvasta-tin on high glucose-induced ROS production and NADPH oxidase activation were largely impaired when the cells were trans -fected with RXRαsiRNA.However , the effect of atorvastatin was significantly strengthened when RXRαwas over-expressed in the HUVECs transfected with RXRαplasmid.CONCLUSION: Atorvastatin inhibits atherogenesis by depressing high glucose-induced oxidative stress in diabetic ApoE-/-mice with fat-rich diet.The anti-oxidative stress effect of atorvastatin is mediated by RXRα.

ObjectiveTo observe the clinical efficacy of acupuncture at cranial sutures (cranial acupuncture) plus rehabilitation training in treating cerebral infarction.MethodSixty patients with cerebral infarction were randomized into an acupuncture-rehabilitation group (cranial acupuncture plus rehabilitation training) and a rehabilitation group (dryrehabilitation training), 30 cases in each group, to respectively receive cranial acupuncture plus rehabilitation training and dry rehabilitation training. The Fugl-Meyer Assessment (FMA) and Barthel Index (BI) were adopted to respectively evaluate the motor function of limbs and activities of daily living (ADL); the content of hypersensitive C-reactive protein (hs-CRP) was also observed before and after treatment for the evaluation of therapeutic efficacy.ResultThe acupuncture-rehabilitation group wassuperior to the rehabilitation group in improving the motor function and ADL, and down-regulating the hs-CRP content (P<0.05).ConclusionCranial acupuncture plus rehabilitation training is the optimal protocol in treating cerebral infarction, and it canproduce a more significant efficacy than dry rehabilitation training.

Objective To evaluate the role of native ureter for the management of renal transplantation urological complications retrospectively.Method Twenty-six renal transplant recipients (18 males and 8 females) experienced the following urological complications:upper ureter injury,urinary leaks and moderate or severe ureteric obstructions secondary to ureterovesical anastomotic stricture.These complications have been managed with minimally invasive endourologic techniques or percutaneous nephrostomy as the first-line intervention.While endourologic treatment did not succeed,and the recipients have been treated with intraperitoneal open surgical correction.Urinary continuity was established by pyeloureterostomy or ureteroureterostomy using recipient native ureter.A pigtail ureteral stent was placed with the tip positioned in the pelvis of the graft and native bladder and removed after 4 to 6 weeks.Result The recipients were managed successfully during a follow-up period of 6 months to 6 years without occurrence of urological complications.One case underwent graft loss due to chronic rejection 5 years later postoperation,and the rest developed stable renal function with baseline serum creatinine.Conclusion Excellent outcomes have been achieved by the use of recipient native ureter for the management of urological transplant complications.This simple and efficient procedure should be considered as the superior choice for the recipients who experienced urological complications while less invasive endourologic techniques failed.

Objective:To investigate the changes of cyclooxygenase-2 (COX-2) expression in the spinal cord dorsal horn atfer intrathecal a speciifc p38MAPK inhibitor-SB203580 on neuropathic pain in rats induced by chronic constrictive injury (CCI) to the sciatic nerve. Methods:Twenty-four male SD rats atfer intrathecal catheter placement were randomly divided into 4 groups:a sham group with sham surgery, the neuropathic pain model of a NS group, a DMSO group and an SB group were established by CCI to sciatic nerve. NS or DMSO or SB203580 was injected IT NS or 2%DMSO or SB203580 twice a day for 5 consecutive days starting at 6th day when the model of chronic constrictive injury was established. Mechanical stimuli were measured before the surgery and on 1st, 3rd, 5th, 7th, 9th, and 11th day atfer the surgery. hTen all rats were sacriifced and the lumbar segment of spinal cord was removed to determine the COX-2 expression in the dorsal horn by immunocytochemistry. Results:Day 1 to 11 after the surgery, the threshold to mechanical on the surgery side was signiifcantly lower in the NS group and the DMSO group than in the sham group. Day 7 to 11 atfer the sugery, the threshold to mechanical on the surgery side was signiifcantly lower in the SB group than in the NS group and the DMSO group. hTe expression of spinal COX-2 was higher in the NS group and the DMSO group than in the sham group, but lower in the SB group than in NS group and the DMSO group. Conclusion:Intrathecal administration of SB203580 has signiifcant analgesic effect in the CCI rat model. Expression of COX-2 is signiifcantly reduced when p38MAPK is inhibited by intrathecal SB203580, and p38MAPK stimulation is essential for COX-2 expression.

Objective To analyze the curative effect of simultaneous liver and kidney transplantation (SLKT) for patients with end-stage liver and kidney diseases and liver cirrhosis patients with hepatorenal syndrome.Methods All SLKTs (n=21) performed at our center from January 1999 to December 2010 were reviewed and SLKT outcomes were compared with those of kidney transplantation (KT) (n=609) and liver transplantation (LT) (n=133) performed during the same period.Results There were 3 deaths due to infection 2 weeks, 6 months and 5 years respectively after operation. One patient died due to multiple organ dysfunction syndrome 2 weeks after operation. One patient was dead 5 years after operation because of rejection. MELD level between SLKT and LT had no significant difference, but serum creatinine in SLKT group was significantly higher than in LT group (516.0±329.9 vs 111.4±138.1 mmol/L, P<0.01). The 1-year acute kidney rejection rate and rate of delayed graft function (DGF) of the kidney had no significant difference between SLKT group (0 vs 9.5 %) and KT group (6 % vs 17.3 %). There was no significant difference in one-, 3- and 5-year patient survival rate between SLKT group (87.7 %, 67.8 % and 67.8 %) and LT group (84.2 %, 73.5 % and 69.4 %).Conclusion SLKT is a safe and effective treatment for end-stage liver and kidney diseases.

Objective To report the modified technique and the short-term results of simultaneous pancreaticoduodenum-kidney transplantation (SPK) with the enteric drainage (ED) of exocrine secretions. Method Between June 2000 and Jan 2006, thirty-five patients with diabetes and uremia underwent SPK. The pancreas graft is placed intraperitoneally with its exocrine secretions drained into the proximal jejunum without Roux-en-Y procedure. The mean cold ischemic times of kidney was 6. 92?2. 17 hours and that of pancreas, 9. 65?2. 02 hours. Quadruple immunosuppressive therapy with antilymphocyte globulin or antiCD25 monoclonal antibody ( Zenapax ) , tacrolimus, mycophenolate mofetil and steroids was adopted. Results Postoperative patient and graft survival rates were 97. 3%. All patients achieved insulin-free euglycemia at 8.3?4.5 days postoperatively. Preoperative patient's mean fasting insulin and C-peptide values were 7.45?7. 35 mU/L and 5. 68?4. 66 mU/L. After operation, patients had fasting insulin and C-peptide values of 11. 9?5.70 mU/L and 5. 57?4. 90 mU/L, respectively, which peaked to an insulin level of 57. 9?46.6 mU/L and a C-peptide level of 11.75?6.99 mU/L with stimulation. The pancreas grafts also functioned well as evidenced also by normal serum amylase values of 92. 10?12. 24 U/L on 10th postoperative day. There were five cases of delayed renal graft function. All other patients achieved immediate renal graft function. No graft losses occurred due to leakage or intra-abdominal infection. The most commn surgical complications were wound infection (n - 11) , enteric anastomostic hemorrage ( n = 5) , and peri-renal hemorrage (n =2). Conclusions SPK is a effective treatment option for patients with diabetes mellitus and uremia. Enteric exocrine drainage by direct side-to-side anastomosis (without Roux-en-Y loop) seems to be a simple and reliable technique.