Objective:To explore diagnostic value of dynamic electrocardiogram (DCG) combined esophageal electro‐physiological examination (EEE) for sick sinus syndrome (SSS) .Methods :A total of 74 cases suspecting SSS ,who presented 24h mean heart rate <55 beats/min in DCG ,were selected .After DCG examination ,all subjects received EEE . Diagnostic value of single and combined examinations wereexplored .Results:Compared withthe SSS positive rate of single DCG and single EEE(87.8% ,86.5% ) ,theSSS positive rate ofDCG combined EEE(97.3% ) was sig‐nificantly rose ,P<0.05 both .Conclusion:Dynamic electrocardiogram combined esophageal electrophysiological ex‐amination can evaluate sinus node function from different angles ,which can significantlyincrease SSS diagnose rat .

Objective To analyze the correlation of urinary angiotensinogen (AGT) with clinical index of kidney injury and intrarenal renin-angiotensin system (RAS) activity in chronic kidney disease (CKD) patients. Methods Urinary or plasma renin activity, AGT, angiotensin Ⅱ (Ang Ⅱ ), aldosterone were measured by RIA or ELISA in 129 CKD patients. Expression of intrarenal renin, AGT, Ang Ⅱ and angiotensinⅡ receptor was examined by immunohistochemistry staining (IHCS) in 73 CKD patients undergoing renal biopsy. Correlation of urinary AGT with other indexes was performed. Results Average urinary AGT in 129 CKD patients was (159.08 ± 125.18) μg/g Cr, Scr was (113.20± 105.05)μmol/L, and urinary AGT was positively correlated with Scr (r=0.51, P<0.01). Average estimated glomerular filtration rate (eGFR) was (58.52±27.15) ml·min-1·(1.73 m2)-1, which was negatively correlated with urinary AGT (r=-0.55, P<0.01). Average urinary protein was (2.03±2.65) g/24 h, which was positively correlated with urinary AGT (r=0.30, P<0.01). Average urinary Ang Ⅱ was (164.71 ±139.25) ng/g Cr, which was positively correlated with urinary AGT (r=0.20, P<0.05). Average urinary type Ⅳ collagen was (447.60± 800.66) μg/g Cr, which was positively correlated with urinary AGT (r=0.47, P<0.01). Average urinary soduim was (162.17±81.61) mmol/24 h, which was negatively correlated with urinary AGT (r=-0.20, P<0.05). Multiple regression analysis indicated that low eGFR (P<0.01), high Scr (P< 0.01), high urinary protein (P<0.05), high urinary Ang Ⅱ (P<0.05) and high urinary type Ⅲ collagen (P<0.01) were significantly correlated with high urinary AGT. In renal tissues of CKD patients, there was positive correlation of urinary AGT with positive IHCS area of AGT (r=0.45, P< 0.01), Ang Ⅱ (r=0.52, P<0.01) and angiotensin Ⅱ type 1 receptor (r =0.28, P <0.05). Conclusions Urinary AGT level may indicate the kidney injury severity, especially in chronic kidney injury, and may be used as a non-invasive marker of intrarenal Ang Ⅱ activity in CKD patients.

Objective To synthesize Wye-125132,an inhibitor of mTOR,and to establish a synthetic route for industrial production.Methods Barbituric acid was used as the raw material to synthesize the intermediate 2, 4, 6-trichrolo-pyrimidine-5-carbaldehyde 2 via Vilsmeier-Haack and chlorination reaction, while intermediate 5 was prepared via 3-step reaction from 1,4-dioxaspiro-[4,5]decan-8-one.The condensation of 2 and 5 was followed by substitution reaction to obtain the key intermediate 7.The side chain 9 was prepared by 3-step reaction from bromine aniline.Then the title product 1 was obtained with the reaction of Suzuki cross-coupling of 7 and 9.The structures of intermediate and target compounds were confirmed by MS and 1 H-NMR.Results and Conclusion Compared with the method reported in the literature,this new synthesis method possesses some advantages, such as ready availablity of raw materials, simple operation, mild reaction conditions and easy disposal of products.The total yield is 13.2%,and the purity of the target compound is 99.77%.

Objective To study the effects of experiment-related factors on hematological parameters in SD rats, analyze the data difference and causes, understand the effects of anesthetics and stress responses on the physiological aspects of animals, and to provide a reference for the standardization of animal welfare and compound toxicity testing methods.Methods According to gender (A), fasting time (B), anesthesia (C) and blood collection mode (D), SPF SD rats were divided into 24 groups.Blood samples were collected from each group.Then, red blood cell count, hemoglobin levels, white blood cell count and classification indicators were measured.Results The primary and secondary order of the factors affecting the white blood cell count was D > C > A > B, and the levels of white blood cell count of each factor were male rats > female rats, and venous blood > arterial blood, chloral hydrate > pentobarbital sodium > no anesthesia.The primary and secondary order of the factors affecting the white blood cell classification was C > D=A=B, and factors affecting the levels of white blood cell classification were chloral hydrate > pentobarbital sodium > no anesthesia.The primary and secondary order of the effects of the factors on the red blood cell count and hemoglobin level was C > D=A=B, and the levels of red blood cell count and hemoglobin level were pentobarbital sodium > chloral hydrate> no anesthesia.There was no significant difference in the blood indexes between the different fasting time groups.Conclusions There is no effect of fasting on hematological parameters, but there are differences in the blood parameters between arteries and veins.The effect of chloral hydrate anesthesia on the count and classification of white blood cells is greater than that of pentobarbital sodium.The effect of chloral hydrate anesthesia on the red blood cell count and hemoglobin level is greater than that of pentobarbital sodium.The two kinds of anesthesia methods have their own advantages and disadvantages.

Objective To investigate the roles of microRNA-382 (miR-382) in the pathogenesis of renal tubulointerstitial fibrosis (TIF).Methods Human kidney epithelial cells (HK2)transfected with miR-382 inhibitor (antagomiR-382) were used to examine the effect of miR-382 abundance on cell polarity,as well as to test the complementary relationship between miR-382 and its predicted target gene heat shock protein 60 (HSPD1),which was further verified by 3'-untranslated region luciferase assay and site-directed mutagenesis.The role of miR-382 played in the development of renal interstitial fibrosis and redox regulation was examined in a mouse unilateral ureteral obstruction (UUO) model.Locked nucleic acid (LAN)-modified anti-miR-382 was intravenous delivered via tail vein 30 min prior to UUO,and repeated the dosage 24 h after the surgery.For clinical verification,renal biopsy specimens from 12 IgA nephropathy (IgAN) patients were collected,6 patients with moderate to severe TIF and 6 patients without TIF.The relative abundance of miR-382 and HSPD1 protein was analyzed by using in situ hybridization and immunohistochemistry.Results HSPD1 was confirmed to be a new,direct target gene of miR-382 by in vitro 3'-untranslated region luciferase assay and sitedirected mutagenesis.The development of epithelial transition in HK2 cells was accompanied with upregulation of miR-382 [(6.54±0.96) vs (1.12±0.26),P ＜ 0.05].Blocking the expression of miR-382 could reversed the progression of epithelial transition partially.In UUO mice the abundance of miR-382 was up-regulated [(6.89 ± 2.47) vs (1.00±0.42),P ＜ 0.01] while HSPD1 and Trx were downregulated compared with the sham group.Down-regulation of miR-382 was associated with significant decrease in TIF,but increase in HSPD1 and thioredoxin protein compared with UUO group [HSPD1:(0.34±0.10) vs (0.14±0.05);Trx:(0.79±0.18) vs (0.36±0.16);all P ＜ 0.05].The expression of miR-382 was up-regulated and HSPD1 was significantly down-regulated in IgAN patients with TIF.Conclusions miR-382 play an important role in renal tubulointerstitial fibrosis in human and mice.HSPD1 is one of the target genes of miR-382.The down-regulation of HSPD1 and the decrease ability of anti-oxidative stress may be the important mechanism of miR-382 involved in renal tubulointerstitial fibrosis.

Objective To investigate the situation of prevalence,treatment and control of hypertension in patients with chronic kidney disease(CKD)by CROSS-sectional study. Methods Nine hundred out-patients with CKD in our department from November 2006 to March 2007 were enrolled in the study,including 480 male and 420 female.Among 900 CKD cases,354 patients underwent maintenance dialysis,including 228 on hemodialysis and 126 on peritoneal dialysis.Results The prevalence of hypertension in CKD patients was 80.2%(nude 83.5%vs female 76.4%,P<0.01).The prevalence of hypertension in patients on dialysis was significantly higher than that in non-dialysis patients(90.1%vs 73.8%,P<0.01),but there was no significant difference between hemodialysis and peritoneal dialysis cases.Antihypertensive treatment rate was 92.4%in CKD patients with hypertension.and was significantly higher in patients on dialysis than that in non-dialysis patients(95.6%vs 89.8%.P<0.01).The control rate according to current recommendations for CKD patients (BP<130/80 mm Hg) was very low. Control of both SBP and DBP was only achieved in 20.4% of non- dialysis patients. The control rate of hypertension (BP< 125/75 mm Hg) in patients with proteinuria >1 g/24 h was 8.4%. The proportion of dialysis patients with BP<140/90 mm Hg was significantly lower than that of non-dialysis patients (45.2% vs 55.5%, P<0.01). The percentage of hemodialysis patients with BP < 140/90 mm Hg was significantly higher than that of peritoneal dialysis patients (49.8% vs 36.5%, P<0.05). The prevalence of hypertension was associated with the decrease of renal function and the increase of age. The prevalence of hypertension in diabetic nephropathy was higher than that in primary glomerular diseases. Patients received 1, 2, 3 and 4 or more kinds of antihypertensive drugs accounted for 37.2%, 37.5%, 19.3% and 5.9% respectively. The combination of calcium channel blocker (CCB) and renin-angiotensin-aldosterone system (RAAS) inhibitors was more frequently used in CKD patients. The CCB was the most frequently prescribed drug (74.1% ), followed by angiotensin Ⅱ receptor blockers (ARB) (48.4%), angiotensin-converting enzyme inhibitors (ACEI) (25.6%) and alpha, beta-blockers (24.7%). Conclusions The prevalence of hypertension in CKD patients is quite high, which is associated with the progression of renal function, increase of age, the type of underlying kidney disease, obesity and diabetes mellitus. The control of hypertension is unsatisfied in CKD patients, especially in dialysis patients and those with overt proteinuria.

ObjectiveTo compare the efficacy and safety of intermittent patient-initiated single-dose antibiotic prophylaxis and continuous antibiotic prophylaxis for the prevention of recurrent urinary tract infection (UTI) in postmenopausal women. MethodsA randomized controlled clinical trial was conducted for the prevention of recurrent urinary tract infection. Single dose of antibiotic was given every night in continuous antibiotic prophylaxis group and every time after exposure to conditions predisposed to UTI in intermittent antibiotic prophylaxis group. The duration of prevention was 12 months in both groups. ResultsThe effective rates of intermittent antibiotic prophylaxis and continuous antibiotic prophylaxis were 71.0% and 81.8% respectively (P＞0.05). The incidence of gastrointestinal adverse reaction in intermittent antibiotic prophylaxis group was significantly lower than that in continuous antibiotic prophylaxis group (7.7% vs 28.6%,P＜0.05). ConclusionsCompared with continuous antibiotic prophylaxis, intermittent patient-initiated single-dose antibiotic prophylaxis is a better prophylaxis with less gastrointestinal adverse reactions for the prevention of recurrent urinary tract infection in postmenopausal women.

Objective To observe the efficacy of the treatment of mycophenolate mofetil (MMF) combined with prednisone on steroid-resistant idiopathic membranoproliferative glomerulonephrifis (IMPGN) patients with moderate to severe proteinufia. Methods Thirteen cases were diagnosed as IMPGN by renal biopsy after excluding secondary factors. Among 13 patients, 9 had severe proteinuria and another 4 had moderate proteinuria, 9 with hypertension and 11 with decreased renal function. Before MMF therapy, all of the cases were resistant to the treatment of glucocorticoid (prednisone 1 mg·kg-1·d-1) for 8 weeks or more. The dose of MMF was 1.5 g/d. Patients were followed up every month for blood pressure, urinary protein excretion, liver and kidney function, complete blood count, and adverse effects. Results At the initiation, the 24 h urinary protein excretion was (4.1±1.4) g, Scr (131.0±44.9) μmol/L, and estimated glomerular filtration rate (eGFR) (63.3±26.8) ml·min-1·(1.73 m2)-1. After prednisene therapy for at least 2 months, the 24 h urinary protein excretion (4.2±1.5) g, Ser (133.2±52.8)μmol/L and eGYR (63.3±27.1) ml·min-1·(1.73 m2)-1did not change significantly. After 3 months of the addition of MMF, 24 h urinary protein excretion declined slightly [(3.8±1.2) g, P>0.05]. After 6 months, 24 h urinary protein excretion declined significantly [(2.5±0.9) g, P<0.05], with decrease in Set and eGFR[(97.2±27.3) μmol/L and (81.3±24.2) ml·min-1·(1.73 m2)-1, P<0.05)]. At the end of 1 year, 24 h urinary protein excretion was only (1.5±0.6) g(P<0.01 ), Ser and eGFR were (95.9±22.5)μmol/L and (81.2±23.8) ml·min-1·(1.73 m2)-1(P<0.01). All the patients experienced a partial remission of proteinuria (urinary protein excretion decreased by 50% or more). Adverse event including stomach upset was found in 1 patient. Conclusion MMF combined with glucosteroids can effectively decrease proteinuria and improve renal function without obvious side effect in steroid-resistant IMPGN.

Objective To explore the effect of hypoxia inducible factor-1α silencing by siRNA on proliferation, apoptosis and necrosis of human renal proximal epithelial cell ( HK-2 )under hypoxia. Methods CoCl2 was used to mimic hypoxia, and siRNA technique was used to silence HIF-1α. HK-2 cells were divided into five groups, including normal culture group,hypoxia culture group, transfection reagent group, negative control group and HIF-1α siRNA group.MTT assay was used to detect the growth inhibition ratio of cells. TUNEL and caspase-3 quantity was used to detect apoptosis. LDH activity in supernatant was detected to evaluate cell necrosis.Real-time PCR and Western blotting were used to detect mRNA and protein of HIF-1α, HIF-2α,glucose transporter 1(Glut-1) and vascular endothelial growth factor (VEGF). Results (1) The transfection efficiency of siRNA was 95%-100%. Under normoxia, the efficiency of siRNA silencing HIF-1α gene reached to 70%, while under hypoxia, it was 97%. (2) The growth inhibition ratio of cells in HIF-1α siRNA group was significantly higher than that of other groups including hypoxia culture group, transfection reagent group and negative control group (all P＜0.05). No significant difference was found in apoptotic ratio of the other four groups except normal culture group (P＞0.05). The LDH level in HIF-1α siRNA group was significantly higher than that of hypoxia culture group, transfection reagent group and negative control group (P＜0.05). (3) The expression of HIF1α, Glut-1, VEGF mRNA and protein in HIF-1α siRNA group was significantly lower than that of hypoxia culture group, transfection reagent group and negative control group (P＜0.05). No significant difference was observed on the level of HIF-2α mRNA and protein in the other four groups except normal culture group (P＞0.05). Conclusion HIF-1α gene silencing can inhibit the mRNA and protein expression of Glut-1 and VEGF, and can aggravate growth inhibition and necrosis of HK-2 cells under hypoxia.

Objective To compare the efficacy of different therapies for idiopathic membranous nephropathy (IMN) patients, and to discuss their rationality. Methods The clinicopathological data and therapies of 76 patients with IMN in our hospital was retrospectively analyzed and reviewed, and the efficacy was followed up.According to the different therapies, 76 patients were divided into 4 groups, including symptomatic treatment group, glucocorticoid-alone group, immunosuppressant-alone group, and glucocorticoid in combination with immunosuppressant group (combination group). Comparison and analysis of the efficacy of the different therapies were made. Results (1) The incidence of nephrotic syndrome and 24-hour proteinuria of patients in symptomatic treatment group were significantly lower than those in glucocorticoid-alone group and combination group. (2) The remission rates of 4 groups were 56.3%,73.7%,66.7% and 78.9%, respectively. In general, no statistical differences were observed in the remission rates of patients among the symptomatic treatment group, glucocorticoid-alone group and combination group. The 2-year and 5-year renal survival rates were 89.2% and 79.3%, respectively. (3) Patients in glucocorticoid-alone group and combination group were divided into low-risk, moderate-risk and high-risk patients. No difference in remission rate was observed between the two therapies for low-risk and moderate-risk patients.But for high-risk patients,the remission rate in combination group was significantly higher than that in glucocorticoid-alone group.(4) Patients in glucocorticoid-alone group and combination group were divided into remission subgroup and non-remission subgroup. It showed that only estimated glomerular filtration rate (eGFR) between these two subgroups had statistical difference, and eGFR in non-remission subgroup was lower than that in the remission subgroup. Conclusions For high-risk patients,treatment with glucocorticoid combined with immunosuppressant may improve the remission rate of proteinuria significantly.Glomerular filtration rate before treatments is an important prognostic factor.