Objective To investigate the relationship between the resting heart rate (RHR) and target organ damage (TOD) in elderly patients with metabolic syndrome(MS). Methods 264 elderly patients with MS were divided into four groups according to the level of RHR: RHR1 group, RHR<65 beats/minute (bpm) (46 cases) ;RHR2 group, 65≤RHR<75 bpm (77 cases);RHR3 group, 75 bpm≤RHR<85 bpm (89 cases);RHR4 group, RHR≥85 bpm (52 cases).Electrocardiography, echocardiography, carotid uhrasonography, crcatinine clearance rate (Ccr) and quantitative assay of 24 hours' albuminuria were performed. Results (1) Compared with RHR1, RHR2 and RHR3 groups, RHR4 group showed higher levels of carotid intima-medial thickness (IMT), carotid arterial diameter (CAD), left ventricular mass index (LVMI) and albuminuria(P< 0.05 or P<0.01), and lower levels of left ventricular ejection fraction (LVEF) and Ccr (all P< 0.01). (2) The IMT, CAD, LVMI and albuminuria were positively correlated with RHR (r=0.33, 0.23, 0.61, 0.58, respectively, all P<0.01). However, the LVEF and Ccr were negatively correlated with RHR (r=-0.59, -0.51, all P<0.01). (3) Logistic multivariate analysis showed that RHR and pulse pressure (PP) had effects on myocardial hypertrophy, coronary heart disease, heart failure, cerebral stroke and renal dysfunction(P<0.05 or P<0.01). Except heart failure, PP played a more important role than RHR. Coneinsions RHR may be an independent risk factors for TOD in elderly patients with MS,and RHR regulation is important for the development of MS in the elderly.

Objective To analyze the expression and regulation of components of intrarenal renin-angiotensin system (RAS) and the correlation between intrarenal angiotensin Ⅱ (Ang Ⅱ) expression and clinicopathological injury index in primary IgA nephropathy patients. Methods Expressions of intrarenal RAS components were assessed by immunohistochemistry staining (IHCS). Correlation among intrarenal RAS components and of intrarenal Ang Ⅱ expression with blood pressure, estimated glomerular filtration rate (eGFR), 24-h urinary protein and Katafuchi score in 36 primary IgA nephropathy patients were examined. Results There were positive correlations between positive IHCS area of intrarenal renin and Ang Ⅱ (r=0.43, P＜0.01), angiotensiongen and Ang Ⅱ (r=0.34, P＜0.05). There was negative correlation between positive IHCS area of intrarenal Ang Ⅱ and eGFR (r=-0.61, P＜0.01). There was positive correlation between positive IHCS area of intrarenal Ang Ⅱ and pathological chronicity index (ρ=0.39, P＜0.05), index of interstitial cell infiltration (ρ =0.52, P ＜0.05). Conclusion Expression of intrarenal Ang Ⅱ is positively correlated with expression of intrarenal renin and angiotensinogen, and plays an important role in kidney fibrosis in primary IgA nephropathy.

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.

In the present study, the fluoro-gold(FG) and horseradish peroxidase(HRP) combined tracing method was used to investigate the localization of parasympathetic preganglionic neurons and ascending projection neurons in lumbosacral spinal cord of the rat. FG was injected into the lateral parabrachial nucleus(PBL) or into Barrington's nucleus on one side, and HRP was applied to the contralateral pelvic nerve. The retrogradely FG-labeled neurons were found in bilateral "visceral field" at segments L_5-S_2, and the majority of them were concentrated in the intermediolateral nucleus (IML), and the dorsal commissural nucleus (DCN). In addition to these areas, some labeled neurons were also observed in bilateral lamina I and lateral spinal nucleus (LSN). The parasympathetic preganglionic neurons labeled with HRP were seen in the IML at segments L_6-S_1, occasionally appeared in the intercalated nucleus. In the IML area, HRP-labeled parasympathetic preganglionic neurons were located in its ventral part, however, the localization of FG-labeled neurons projected to the PBL and Barrington's nucleus were mainly found in the dorsal and dorsomedial part of the IML, and a few FG-labeled cells were scattered among HRP-labeled cells. Based on the present and other investigations, the nomenclature, organization and function of the IML and the composition of the LSN were discussed.

A total of 40 patients with COPD (excluding those with correlated/relevant diseases)were measured for inflammation parameters of erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP) after hospital admission and some coagulation/fibrinolysis parameters including D-dimer,thrombinantithrombin (TAT),prothrombin fragment 1 + 2,(tissue plasminogen activator) tPA,plasminogen activator inhibitor 1 (PAI-1),von Willebrand factor (von WF),endothelin receptor A,thromboxane B2,P-selectin and pulmonary arterial pressure (PAP) by ultrasonic cardiography after the settling of the symptons of acute period.All patients were then divided into 2 groups according to PAP [＜ 40 mm Hg (1 mmHg=0.133 kPa) (n=24),＞40 mm Hg (n=16)].The values of CRP and ESRin the group with PAP ＞ 40 mm Hg were significantly higher than those in another group (P =0.044 and P =0.002respectively) while tPA was lower (P =0.04).A moderate positive correlation existed between tPA and TXB2 (r =0.547).Moreover,a highly positive correlation was found between TXB2 and PAl-1 (r =0.929).The results indicated that the COPD patients with pulmonary arterial hypertension (PAH) tend to have a higher level of inflammation,and their fibrinolysis becomes impaired leading to a prothrombotic state.

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 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.