Search

Objectives: To investigate the protective effect of different atorvastatin doses on contrast-induced acute kidney injury and the related mechanism. Methods: Healthy male Sprague–Dawley (SD) rats were randomly divided into the blank control group, experimental control group and different-dose atorvastatin groups. A rat model of contrast-induced acute kidney injury was established. We detected changes in serum creatinine (Scr) and blood urea nitrogen (BUN) before and after model establishment, observed and scored renal tubular injury, analyzed rat renal cell apoptosis, and measure the expression of signal pathway proteins and downstream inflammatory factors. Results: After contrast agent injection, the Scr and BUN levels of the experimental control group were significantly increased, the different doses applied in the atorvastatin group significantly reduced the Scr and BUN levels (p

Full-time clinician educators are becoming more predominant in China, yet their effect is unknown.The purpose of this study was to compare the teaching quality of full-time (FT) faculty with that of part-time (PT) faculty in one Chinese medical school.In 3 consecutive years, 881 3rd year medical students were enrolled and randomly distributed into two groups, being taught by either a FT faculty member or a PT faculty member. Their teaching quality was evaluated with student performance on a written exam, the standardized patient exam, and student satisfaction.The students in the FT group always scored better on the written exam (1st year = 79.82 ± 9.2 vs. 81.26 ± 8.2, p.188; 2nd year = 73.10 ± 9.8 vs. 76.51 ± 7.9, p = .001; 3rd year = 75.15 ± 9.0 vs. 79.51 ± 8.7, p.0001). In the standardized patient exam, the students from FT groups always showed better performance in history taking and physical examination. Students continually gave higher evaluations to FT faculty in questionnaires (1st year = 76.8 ± 6.5 vs. 84.3 ± 2.2; 2nd year = 78.6 ± 3.9 vs. 89.7 ± 4.2; 3rd year = 75.8 ± 3.9 vs. 88.5 ± 3.5, all ps.001).The teaching quality of FT faculty in clinical-skills training is better than PT faculty in this study.

Background and Purpose: The exact mechanism of protease-activated receptors (PARs) on pacemaker activity of interstitial cells of Cajal (ICCs) has not been reported. We investigated the effects on pacemaker activity by the activation of PARs and its signal mechanisms in colonic ICCs. Methods: The whole-cell patch-clamp technique, RT-PCR and Ca2+ imaging were used in cultured ICCs from mouse colon. Results: PAR-1 and PAR-2 were expressed in Ano-1 positive ICCs. TFLLR-NH2 (a PAR-1 agonist) and trypsin (a PAR-2 agonist) depolarized the membrane and increased the pacemaker potential frequency. U-73122 (a phospholipase C (PLC) inhibitor) and thapsigargin (a Ca2+ ATPase inhibitor) suppressed the TFLLR-NH2- and trypsin-induced effects on pacemaker potential. TFLLR-NH2 and trypsin also increased intracellular Ca2+ ([Ca2+]i) intensity with increasing of Ca2+ oscillations. Genistein (a tyrosine kinase inhibitor), SP600125 (a JNK inhibitor), CsCl, ZD7288, clonidine (hyperpolarization-activated cyclic nucleotide (HCN) channel blockers), SQ-22536 and dideoxyadenosine (adenylate cyclase inhibitors) suppressed the increased pacemaker potential frequency without effects on depolarization of the membrane induced by TFLLR-NH2 and trypsin. Conclusion: These results suggest that activation of PAR-1 and PAR-2 modulates the pacemaker activity of colonic ICCs through the PLC-dependent [Ca2+]i release pathway. The increased pacemaker potential frequency by PAR-1 and PAR-2 was also dependent on tyrosine kinase, JNK, and HCN activation.

Astragalus mongholicus (AM) derived from the dry root of Astragalus membranaceus Bge. var. mongolicus (Bge.) Hsiao is a widely used traditional Chinese medicine. The present study investigated the potential role of AM on renal fibrosis on a rat model of unilateral ureteral obstruction (UUO). We divided 48 Sprague-Dawley rats randomly into 4 groups: sham-operated group (Sham), untreated UUO group, AM-treated (10 g/(kg x d)) UUO group, and losartan-treated (20 mg/(kg x d)) UUO group as positive control. Haematoxylineosin (HE) and Masson staining were used to study the dynamic histological changes of the kidneys 7 and 14 d after operation. The expressions of fibronectin (FN), type I collagen (colI), hepatocyte growth factor (HGF), transforming growth factor-beta1 (TGF-beta1), and alpha-smooth muscle actin (alpha-SMA) were analyzed by real-time polymerase chain reaction (PCR), immunohistochemistry staining, and Western blot. Results show that, similar to losartan, AM alleviated the renal damage and decreased the deposition of FN and colI from UUO by reducing the expressions of TGF-beta1 and alpha-SMA (P0.05), whereas HGF increased greatly with AM treatment (P0.05). Our findings reveal that AM could retard the progression of renal fibrosis. The renoprotective effect of AM might be related to inhibition of myofibroblast activation, inducing of HGF and reducing of TGF-beta1 expression.

To investigate the possible protective effect and mechanism of ginsenoside Rb1 against oxidative damage and renal interstitial fibrosis on rats with unilateral ureteral obstruction (UUO).In total, 80 male rats were randomly divided into 4 groups, 20 in each group: the sham operated group (SOR), UUO group, UUO with ginsenoside Rb1 treatment group (treated with intraperitoneal injection of 50 mg/ kg daily) and UUO with Losartan treatment group (as the positive control, treated with 20 mg/kg by gastrogavage per day). The rats were randomly sacrificed on day 3, 7 and 14 after surgery, respectively. The histopathologic changes of renal interstitial tissues were observed with Masson staining. The mRNA of transforming growth factor beta 1 (TGF-beta 1), collagen I and fibronectin were reversed transcribed and quantified by Real-time PCR. Enzyme-linked immunosorbent assay was used to quantitatively detect TGF-beta 1 and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. P47phox protein expression was assessed by immunohistochemistry and Western blot analysis.In the UUO model, the obstructed kidney showed typical features of progressive renal tubulointerstitial fibrosis, and the levels of TGF-beta1, collagen I and fibronectin increased (P0.05). As compared with the UUO group, ginsennoside Rb1 significantly inhibited the interstitial fibrosis including tubular injury and collagen deposition, and decreased the levels of TGF-beta1 (P0.05). Ginsenoside Rb1 also inhibited the heme oxygenase (HO-1) and 8-OHdG, two markers of oxidative stress (P0.05). Moreover, ginsenoside Rb1 suppressed the expression of p47phox, a subunit of nicotinamide adeninedinucleotide phosphate (NADPH) oxidase (P0.05).Ginsenoside Rb1 can obviously inhibit renal interstitial fibrosis in rats with UUO, its mechanism possibly via against the oxidative damage and suppressing TGF-beta1 expression.

To evaluate the efficacy and safety of compound Decumbent Corydalis Rhizome (DCR) in treating patients with knee osteoarthritis (OA). Totally 79 patients with knee osteoarthritis were selected from out-patient and inpatient departments of West China Hospital and randomly divided into the test group and the control group. The test group (n = 41) was given Compound DCR with the dosage of 1.8 g · d(-1), while the control group (n = 38) was administered with diclofenac sodium with the dosage of 75 mg · d(-1). After 12 weeks of treatment, the total efficacy rates based on patients/physicians evaluation for experimental and control groups were 68.29%, 63.41% and 71.05%, 63.16%, respectively, without significant difference between the two groups. Both of the two groups showed significant improvements in the main efficacy indexes (pain on walking 20 m) and minor indexes (tenderness on palpation, Western Ontario and McMaster Universities OA index (WOMAC) and Short-Form Health Survey (SF-36 ), but without significant difference in efficacy between them. The incidence of related adverse events was 24.39% in the test group and 47.37% in the control group, respectively, with significant differences between the two groups (P0.05). In the controlled study, compound DCR is as efficient as diclofenac sodium but more tolerable, with a good clinical application prospect.

To investigate the role of endogenous hydrogen sulfide (H2S) in erectile dysfunction (ED) induced by androgen deficiency.We randomly divided 30 eight-week-old healthy male SD rats into six groups: 2-week control (A), 4-week control (B), 2-week castration (C), 4-week castration (D), 2-week castration + androgen replacement (E), and 4-week castration + androgen replacement (F), those in groups E and F subcutaneously injected with testosterone propionate (TP) at the physiological dose of 3 mg/kg per day after castration, while those in the other groups with isodose oil instead. At 2 and 4 weeks after operation, we determined the level of serum testosterone (T) , intracavernous pressure (ICP) , mean carotid arterial pressure (MAP) of the rats, measured the concentration of H2S in the plasma and corpus cavernosum tissue, and detected the expressions of cystathionine-P3-synthase (CBS) and cystathionine-gamma-lyase (CSE) by immunohistochemistry and Western blot.The serum T level was significantly lower in group C ([0.63 +/- 0.15] nmol/L) than in A ( [ 16.55 +/- 4.17] nmol/L) and E ( [ 18.99 +/- 4.62] nmol/L) (P0.05), as well as in group D ([0.70 +/-0.22] nmol/L) than in B ([15.44 +/-5.18] nmol/L) and F ([20.99 +/-6.41] nmol/L) (P0. 05) , and so were ICP/MAP after 5 and 7 V electrical stimulation of the pelvic ganglia (P0. 05) , H2 S concentration (P0.05), and the expressions of CBS and CSE (P0.05). The expressions of CBS and CSE proteins were also significantly decreased in group C as compared with D (P0.05).The reduced expressions of CBS and CSE may inhibit the H2 S signaling pathway, which might be one of the mechanisms underlying androgen deficiency-induced ED in rats.

To analyze the expression of Gaq in peripheral blood T lymphocytes of the patients with polymyositis (PM) and its correlation with disease activity evaluated by the clinical markers [manual muscle test (MMT),myositis disease activity assessment (MDAA),creatine phosphokinase (CK), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP)].Blood samples were obtained from 30 patients with first onset PM and 30 healthy volunteers. Peripheral blood mononuclear cells (PBMCs) from these patients were collected and CD3+ T cells from PBMCs were sorted out with magnetic beans. The mRNA and protein expression levels of Galphaq in T cells were measured by RT-PCR and Western blot. Student's unpaired 2-tailed t-test was applied to identify Galphaq expression difference between PM patients and healthy controls. Pearson's correlation between Galphaq mRNA expression of PM and clinical evaluation markers MMT, MDAA, CK, ESR or CRP was determined.Compared to health control, PM patients had significantly lower expression levels of Galphaq protein and mRNA in peripheral blood CD3+ T cells (P0. 001). Negative correlation was found between Galphaq mRNA level and MMT (r= -0. 704, P0. 001), MDAA (r= -0. 793, P0. 001) or CK (r= -0. 670, P0. 001), and no correlation was found between Galphaq mRNA level and ESR or CRP.Galphaq expression in T cells of PM is lower than that in normal control and has negative correlation with PM disease activity.

To study predominant risk factors for survival in idiopathic inflammatory myopathies (JIM).The clinical data of 163 cases of IIM were reviewed, who received the diagnosis and treatments in West China Hospital from January 1997 to December 2010. Kaplan-Meier survival curve was used for the survival analysis of these patients with IIM. Univariate and multivariate analysis of risk factors for survival in the patients with IIM were carried out by Log-rank test, univariate Cox regression analysis and Cox regression model respectively.There were 21 death occured among 163 patients with IIM, and the estimated 3, 5, 10-year survival rate was 93%, 89%, 80% respectively. The mortality of the patients with dermatomyositis (DM) or amyophathic dermatomyositis(ADM) increased significantly when compared with polymyositis (PM, P=0. 033, P= 0. 06). The mortality of IIM patients complicated with tumor or cadiovascular involvement was much higher than that of those patients without any complications (P0. 001, P=0. 015). Tumor and cadiovascular involvement were two independent risk factors for the survival of IIM individuals.DM and ADM have much unfavorable prognosis than PM. Tumor and cadiovascular involvement are two major risk factors for the survival of IIM patients.

To identify risk factors associated with cardiac involvement (CI) in patients with dermatomyositis/polymyositis (DM/PM).Medical records of 129 DM/PM patients were reviewed retrospectively. The risk factors associated with CI in those patients were screened through Xt tests or independent tests before a multivariate logistic regression analysis was performed. ROC curves were constructed to determine diagnostic values of the identified risk factors.CI occurred in 59 (45. 74%) of DM/PM patients, with 41 (69. 49%) showing electrocardiographic (ECG) abnormality; 25 (42. 37%) showing ultrasonic cardiogram (UCG) abnormality; 8 (13. 56%) being diagnosed with heart failure, and 2 (3. 39%) being diagnosed with myocardial infarction. Eight (13.56%) of the patients with CI died. CI was more likely to occur in patients with an older age, having interstitial lung disease, antinuclear antibody (ANA) positive, and anti-Jo-1 antibody positive (P0.05). The logistic regression analysis revealed that interstitial lung disease (beta=1. 554), aspartic aminotransferase/creatine kinases (AST/CK) ratio (beta=1.189), positive ANA (beta= 1. 172) and age (beta=0.042) were risk factors associated with CI (P0. 05). Notable areas under ROC curve (0. 642) was found for AST/CK in determining CI in DM/PM patients (P0. 05), albeit with low accuracy. A cut-off of AST/CK ratio at 0. 312 was identified as a reference point for determining CI in patients with DM/PM.Cardiac involvement is the most common complication of DM/PM, although the majority are subclinical. ECG and UCG are common tools for diagnosing cardiac involvement. Interstitial lung disease, AST/CK ratio, positive ANA and age are predictors of CI in DM/PM patients.

To investigate the clinical characteristics, pathogen constitution and their tolerance to antibiotics in idiopathic inflammatory myopathies (IIM) patients complicated with pneumonia and the associated risk factors.The clinical data and pathogen test results of 93 IIM patients with pneumonia and 52 IIM patients without pneumonia (control group) were retrieved and compared.Age of onset and interstitial lung disease were identified as risk factors associated with IIM complicated with pneumonia. Gram negative bacteria were the most common pathogen. Klebsiella pneumoniae was the most common bacteria and Candida albicans was the most common fungus causing infections in the IIM patients, which were relatively sensitive to the third- and fourth-generation of antibiotics such as cephalosporin, fluoroquinolones and aminoglycoside.Older patients with interstitial lung disease are prone to having pneumonia, especially those caused by gram negative bacteria and other atypical pathogens. Timely and reasonable anti-infection treatment is essential.

To compare the clinical values of four different criteria for diagnosing idiopathic inflammatory myopathy (IIM).The four different criteria published in 1975, 1995, 1997 and 2004 were applied to 94 IIM patients and 98 patients with other myopathies in West China Hospital.The sensitivity of the four criteria for diagnosing IIM was 56. 4% (1975), 87. 2% (1995), 61.7 % (1997), and 52. 1% (2004) respectively. The specificity of the four criteria for diagnosing IIM was 78. 6% (1975), 20. 4% (1995), 78. 6% (1997), and 90. 8% (2004) respectively. The Youden index was 35.0% (1975), 7.6% (1995), 40. 3% (1997), and 42.9% (2004), with an odd product of 4. 74 (1975), 1. 75 (1995), 5. 91 (1997) and 10. 77 (2004) respectively. The Kappa value of the four criteria was 0. 351 (1975, P0.05), 0. 075 (1995, P0. 05), 0. 404 (1997, P0.05 ) and 0. 433 (2004, P0.05), and their area under the ROC curve was 0. 675 (1975, P=0. 00), 0. 538 (1995, P=0.36),0. 701 (1997, P=0.00) and 0. 715 (2004, P=0.00) respectively.The 2004 criteria have a better value in diagnosing IIM.

The objective of the study was to investigate the effectiveness and efficacy of the randomized, parallel, and controlled trial of Traditional Chinese Medicine, general acteoside of Rehmanniae leaves, compared with piperazine ferulate in the treatment of primary chronic glomerulonephritis. Rehmanniae leaves and piperazine ferulate can reduce proteinuria and erythrocyturia effectively in the treatment of primary chronic glomerulonephritis. A total of 400 patients diagnosed with primary chronic glomerulonephritis were recruited from outpatient clinics and were randomly assigned to the treatment group (general acteoside of Rehmanniae leaves, two 200mg tablets, bid) or the control group (piperazine ferulate, four 50-mg tablets, bid ). The primary outcomewas 24-h urinary protein. Secondary outcome measures included estimated glomerular filtration rate (eGFR), erythrocyturia, and electrolytes. After 8 weeks of treatment, the treatment group and the control group showed amean reduction in 24-h proteinuria of 34.81% and 37.66%. The 95% CI of difference of the mean reduction in 24-h proteinuria between the two groups was [-11.50%, 5.80%]. No significant differences were found between the two groups in the erythrocyturia reduction. Neither group showed obvious changes between baseline and 8 weeks in eGFR or electrolytes. Adverse events occurred at a similarly low rate in the treatment group (1.5%) and control group (2.5%, P = 0.7238). Both general acteoside of Rehmanniae leaves and piperazine ferulate can reduce proteinuria and erythrocyturia effectively in the treatment of primary chronic glomerulonephritis.Key Words: Chronic glomerulonephritis; General acteoside of Rehmanniae leaves; Piperazine ferulate; Randomized controlled trials

Interstitial lung disease (ILD) is a common and severe complication of idiopathic inflammatory myopathies (IIM). The aim of our study was to identify risk factors for ILD by evaluating both clinical and biochemical features in IIM patients with or without ILD. From January 2008 to December 2011, medical records of 134 IIM patients in our rheumatology unit were reviewed. The patients were divided into ILD group (83 patients) and non-ILD group (51 patients). The clinical features and laboratory findings were compared. The univariable analyses indicated that arthritis/arthralgia (54.2% versus 17.6%,P<0.05), Mechanic’s hand (16.9% versus 2.0%,P<0.05), Raynaud’s phenomenon (36.1% versus 2.0%,P<0.05), heliotrope rash (44.6% versus 19.6%,P<0.05), fever (43.4% versus 21.6%,P<0.05), elevated ESR (60.2% versus 35.3%,P<0.05), elevated CRP (55.4% versus 31.4%,P<0.05), or anti-Jo-1 antibody (20.5% versus 5.9%,P<0.05) were risk factors for developing ILD in IIM. Multivariable unconditional logistic regression analysis that showed arthritis/arthralgia (OR 7.1, 95% CI 2.8–18.1), Raynaud’s phenomenon (OR 29.1, 95% CI 3.6–233.7), and amyopathic dermatomyositis (ADM) (OR 20.2, 95% CI 2.4–171.2) were the independent risk factors for developing ILD in IIM.

Objective. To analyze serum interleukin-6 (IL-6) expression level and its clinical significance in patients with dermatomyositis.Methods. Blood samples from 23 adult patients with dermatomyositis (DM), 22 with systemic lupus erythematosus (SLE), 22 with rheumatoid arthritis (RA), 16 with Sjögren's syndrome (SS), and 20 healthy controls were collected. The IL-6 concentration was detected by chemiluminescence immunoassay. Correlations between IL-6 expression levels and clinical features or laboratory findings in patients with DM were investigated.Results. IL-6 expression level of DM patients was significantly higher than that of normal controls, significantly lower than that of RA patients, and slightly lower than that of SLE or SS patients with no significant differences. The incidence of fever was significantly higher in the IL-6 elevated group. Serum ferritin (SF) and C-reactive protein (CRP) were positively correlated with IL-6.Conclusions. IL-6 plays a less important role in DM than in RA. IL-6 monoclonal antibodies may have poor effect in patients with DM.

This study aims to assess the efficacy and safety of Rehmannia glutinosa acteosides used in combination with the angiotensin receptor blocker irbesartan to treat primary chronic glomerulonephritis. A total of 479 patients diagnosed with primary chronic glomerulonephritis were recruited from outpatient clinics and were randomly assigned to the treatment group (Rehmannia glutinosa acteosides, two 200-mg capsules, bid; and irbesartan, one 150-mg tablet, qd) or the control group (irbesartan, one 150-mg tablet, qd). The primary outcome was 24-h urinary protein. Secondary outcome measures included blood pressure, estimated glomerular filtration rate, erythrocyturia, serum alanine aminotransferase, aspartate transaminase and electrolytes. After 8 weeks of treatment, the treatment group showed a mean reduction in 24-h proteinuria of 36.42% compared to baseline, which was significantly higher than the mean reduction from baseline of 27.97% in the control group (P = 0.0278).Adverse drug reactions occurred at a similarly low rate in the treatment group (0.4%) and control group (1.2%, P = 0.3724). In the treatment of chronic glomerulonephritis, the combination of Rehmannia glutinosa acteosides and irbesartan can reduce proteinuria more effectively than irbesartan alone.

Interstitial cells of Cajal (ICC) are the pacemaker cells that generate the rhythmic oscillation responsible for the production of slow waves in gastrointestinal smooth muscle. Spingolipids are known to present in digestive system and are responsible for multiple important physiological and pathological processes. In this study, we are interested in the action of sphingosine 1-phosphate (S1P) on ICC. S1P depolarized the membrane and increased tonic inward pacemaker currents. FTY720 phosphate (FTY720P, an S1P(1,3,4,5) agonist) and SEW 2871 (an S1P(1) agonist) had no effects on pacemaker activity. Suramin (an S1P(3) antagonist) did not block the S1P-induced action on pacemaker currents. However, JTE-013 (an S1P(2) antagonist) blocked the S1P-induced action. RT-PCR revealed the presence of the S1P(2) in ICC. Calphostin C (a protein kinase C inhibitor), NS-398 (a cyclooxygenase-2 inhibitor), PD 98059 (a p42/44 inhibitor), or SB 203580 (a p38 inhibitor) had no effects on S1P-induced action. However, c-jun NH(2)-terminal kinase (JNK) inhibitor II suppressed S1P-induced action. External Ca(2+)-free solution or thapsigargin (a Ca(2+)-ATPase inhibitor of endoplasmic reticulum) suppressed action of S1P on ICC. In recording of intracellular Ca(2+) ([Ca(2+)](i)) concentration using fluo-4/AM S1P increased intensity of spontaneous [Ca(2+)](i) oscillations in ICC. These results suggest that S1P can modulate pacemaker activity of ICC through S1P(2) via regulation of external and internal Ca(2+) and mitogenactivated protein kinase activation.

To investigate if a-keto/amino acid supplemented low protein diet can slow down the progression of diabetic nephrophathy in comparison with non-supplemented diabetes diet.A prospective, randomized, controlled clinical study was conducted. Twenty three cases of type 2 diabetic nephropathy in IV stage were randomly divided into alpha-keto/amino acid supplemented diet group (trial group) and conventional diabetes diet group (control group), The treatment duration was 52 weeks. 24 h urine protein was measured at 0, 12, 20, 36 and 52 weeks. Before and after the 52 weeks treatment, all the patients received the measurement of glomerular filtration rate (GFR), blood glucose, blood lipids, inflammatory markers, as well as nutritional status.After the treatment for 20, 36, 52 weeks, mean 24 h urine protein decreased significantly in trial groups (P0.05), and 24 h urine protein in trial group were significantly decreased (P0.05) compared with control group in 20 weeks after treatment. Either in trial group or in control group, GFR remained relatively stable during the observation period. Nutrition status, inflammatory markers, and serum calcium, phosphorus levels between the two groups were no significantly difference. The adverse events experienced by the patients in trial group were similar and consistent with the patients underlying renal diseases.Alpha-keto/amino acid can reduce proteinuria more effectively, while improve renal function and nutritional status in diabetic nephropathy patients with well-toleration.

Investigate the effects of compound Radix Notoginseng on renal interstitial fibrosis and kidney-targeting treatment.100 healthy Sprague-Dawley rats were randomly divided into 5 groups: Unilateral ureteral obstruction (UUO) group, sham-operation (SOR) group, Radix Notoginseng (RN) group, compound Radix Notoginseng (CRN) group and Losartan (ARB) group. After operation, RN, CRN and ARB groups were intragastric administrated with RN (3 mL/d), CRN (3 mL/d) and ARB [20 mg/(kg x d)] respectively. Each group randomly included 18 rats for statistical analysis. The histological changes of renal interstitial tissues were observed by HE, Masson and PAS staining. Total kidney collagen content was determined by measuring the amount of hydroxyproline. The mRNA of alpha-SMA, collagen I and fibronectin were reverse transcribed and quantified by real-time PCR. The expression of alpha-SMA protein was assessed by immunohistochemistry and Western blot analysis.In UUO model, the obstructed kidney showed typical features of renal tubulointerstitial fibrosis, such as severe tubular loss, dilation, atrophy, infiltration of inflammatory cells, interstitial matrix deposition (P0.05). Partial correlation assay showed that the expression of alpha-SMA was related to the renal tubular injury (r = 0.55; P0.05). Administration of RN, CRN and ARB improved tubulointerstitial damage and collagen matrix accumulation induced by UUO in different degree. The expression of the alpha-SMA at mRNA and protein levels were significantly increased in the UUO group (P0.05), which was also suppressed by treatment with RN, CRN and ARB in different degree. Moreover, more effective role in preventing fibrosis was observed in CRN group than when compared with that of RN group.RN and CRN can inhibit UUO-induced renal interstitial fibrosis in rats, and CRN treatment is more effective than RN in reducing interstitial fibrosis.

Neurotensin, a tridecapeptide localized in the gut to discrete enteroendocrine cells of the small bowel mucosa, is a hormone that plays an important role in gastrointestinal secretion, growth, and motility. Neurotensin has inhibitory and excitatory effects on peristaltic activity and produces contractile and relaxant responses in intestinal smooth muscle. Our objective in this study is to investigate the effects of neurotensin in small intestinal interstitial cells of Cajal (ICC) and elucidate the mechanism. To determine the electrophysiological effects of neurotensin on ICC, whole-cell patch clamp recordings were performed in cultured ICC from the small intestine. Exposure to neurotensin depolarized the membrane of pacemaker cells and produced tonic inward pacemaker currents. Only neurotensin receptor1 was identified when RT-PCR and immunocytochemistry were performed with mRNA isolated from small intestinal ICC and c-Kit positive cells. Neurotensin-induced tonic inward pacemaker currents were blocked by external Na+- free solution and in the presence of flufenamic acid, an inhibitor of non-selective cation channels. Furthermore, neurotensin-induced action is blocked either by treatment with U73122, a phospholipase C inhibitor, or thapsigargin, a Ca2+-ATPase inhibitor in ICC. We found that neurotensin increased spontaneous intracellular Ca2+ oscillations as seen with fluo4/AM recording. These results suggest that neurotensin modulates pacemaker currents via the activation of non-selective cation channels by intracellular Ca2+-release through neurotensin receptor1.

This study sought to assess the effect of Ginsenoside Rg1 on streptozocin-induced diabetic nephropathy in rats and to unveil the underlying mechanism. Diabetic nephropathy (DN) was induced by intraperitoneal injection of streptozocin (STZ). Eight weeks after drug administration, the rats from each group were sacrificed. Serum creatine (Scr) and 24 hours urine protein, cross reaction protein (CRP) and tumor necrosis factor-alpha (TNF-alpha) were measured at the end of the study. The histological changes of renal interstitial tissues were observed by periodic acid-Schiff staining (PAS). Immunohistochemical method was used to examine the expression levels of ectodermal dysplasia (ED-1). The mRNA of transforming growth factor-beta1 (TGF-beta1) was measured by real-time PCR (RT-PCR), and the protein expression of TGF-beta1 was surveyed by Enzyme-Linked Immunosorbent Assay (ELISA). The renal pathological changes in DN rats given ginsenoside Rg1 treatment were ameliorated, and the expression levels of 24 h urine protein, serum creatinine, CRP, TNF-alpha, ED-1 and TGF-beta1 were significantly lower than those in the diabetic nephropathy group (P0.05). So, we reach a conclusion that, in the experiment, Ginsenoside Rg1 obviously reduced TGF-beta1 expression and the already-mentioned inflammatory reaction factors in the renal tissues and improved the renal pathological changes in DN rats.

To observe the clinical efficacy and safety of Corydalis composite (CDC) combined with methotrexate (MTX) in treating rheumatoid arthritis (RA).Seventy-six RA patients were randomly assigned to 2 groups, 37 in the treated group received the combined therapy, and the 39 received MTX treatment alone, all were treated for 12 weeks. Efficacy of treatment was evaluated adopting the standard of American College of Rheumatology (ACR), taking ACR20 as the chief criterion; ACR50, ACR70 as well as the clinical indexes and items in Health Account Questionnaire (HAQ) as the auxiliary criteria, including joint swelling index, joint tenderness index, holding power, morning stiffness time, resting pain, erythrocyte sedimentation rate (ESR), C-reactive protein. And the adverse reaction was recorded at the same time.After being treated for 4, 8 and 12 weeks, the ACR20 response rate reached 35.14%, 59.46% and 70.27% respectively in patients of the treated group, while that in the control group was 17.95%, 35.90% and 46.15% respectively, significant difference between groups was shown in the outcome of week 8 and 12 (P0.05). ACR50 and ACR70 improving rate at all the time points of observation were increased in the treated group, with the ACR50 improving rate at week 12 higher than that in the control group (43.24% vs. 20.51%, P0.05). As compared with the control group, the improvements in all the auxiliary criteria were more significant in the treated group (P0.05). The incidence of adverse reaction was less in the treated group than in the control group (32.43% vs. 56.41%, P0.05), particularly in term of the damage on liver (0 vs. 10.26%, P0.05).CDC combined with MTX is more effective than MTX alone in treating active RA with less adverse reaction.

To investigate the effects of Ginsenoside Rgl on proteinuria and the expression of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) in rats with diabetic nephropathy (DN).The DN rat model was established by injection of streptozotocin (STZ, 65 mg/kg) in abdominal cavity. Forty Sprague-Dawley male rats were randomly divided into 4 groups: normal group, DN group, Ginsenoside Rgl treatment group and Irbesartan treatment group. The blood glucose was monitored routinely. Twenty-four hours urine protein and serum creatine were measured the day before the rats were killed when the eight weeks of treatments had been completed. The renal pathological and podocyte changes were evaluated. Immunohistochemistry and enzyme-linked immunosorbent assay (ELISA) were performed to examine the protein expression levels of MCP-1 and TNF-alpha, respectively. The mRNA of TNF-alpha and MCP-1 were reverse transcribed and quantified by real-time PCR.The DN rats had increased volume of renal glomerulus, thickened basement membrane, and increased mesenterium mass, as well as some inflammatory cells in renal glomerulus. The number of potocyte decreased significantly in the DN group compared with the normal group (P0.01). Compared with the DN group, the basement membrane became thinning and the number of podocyte increased in the two treatment groups (P0.05). The rats in the DN group and the two treatment groups had significantly higher levels of twenty-four hour urine protein, serum creatine, serum glucose, serum MCP-1 and TNF-alpha than the normal rats (P0.05). The rats in the treatment groups had lower levels of twenty-four hours urine protein and serum creatine than the rats in the DN group (P0.05). But the serum glucose had little changes (P0.05). There was no difference between the two treatment groups. Immunohistochemisty, ELISA and real-time PCR results indicated that the expression levels of MCP-1 and TNF-alpha in the rats in the DN group and the two treatment groups were significantly higher than those in the normal group (P0.05). The rats in the treatment groups had lower levels of expression of MCP-1 and TNF-alpha than those in the DN group (P0.05). The correlation analysis indicated that the levels of MCP-1 and TNF-alpha were positively related to twenty-four hours urine protein (r=0.7802, 0.6963), glomerular sclerosis index (r=0.8296, 0.7413) and thickness of podocyte membrane (r=0.7678, 0.6701, P0.05).Ginsenoside Rgl reduces the expression of MCP-1 and TNF-alpha, repairs the pathological lesions of podocyte and nephron, and reduces the twenty-four hour urine protein rats with diabetic nephropathy.

To study the effect of Astragalus mongholicus (AM) on the expression of transforming growth factor-beta1 (TGF-beta1) in SD rats with unilateral ureteral occlusion (UUO) and to elucidate the mechanisms underlying the renoprotective effects of AM.Fifty-four Sprague-Dawley rats were randomly divided into 4 groups: sham-operation group, the UUO group and AM treatment group. After administration of AM (10 g kg(-1) d(-1)) for 3, 7 and 14 days, the dynamic histological changes of renal interstitial tissues were observed and renal damage including tubular impairment and interstitial fibrosis were quantified on HE and Masson stained tissue sections. The expression of TGF-beta1 and alpha-smooth muscle actin (alpha-SMA) was measured by immunohistochemistry staining sections. The mRNA of TGF-beta1 and alpha-SMA were reverse transcribed and quantified by real-time PCR. The expression of TGF-beta1 protein were assessed by Western blot.Renal damage was exacerbated and the expression of alpha-SMA and TGF-beta1 were all significantly increased in UUO group compared with those of sham-operation group (P0.05) at each time point. Tubular impairment and interstitial fibrosis were alleviated, and up-regulations of expressions of TGF-beta1 and alpha-SMA were significantly suppressed by AM treatment (P0.05).AM can ameliorate renal interstitial fibrosis induced by UUO in vivo. The mechanisms of its antifibrotic effects might be related with the down-regulation of TGF-beta1 expression and suppression of tubular epithelial myofibroblast transdifferentiation in the progress of renal interstitial fibrosis.

To study the effect of Astragalus mongholicus (AM) on the expression of hepatocyte growth factor (HGF) in SD rats with unilateral ureteral obstruction (UUO) and to elucidate the mechanisms underlying the renoprotective effects of AM.Fifty four Sprague-Dawley rats were randomly divided into 3 groups: sham-operation group (SOR), UUO group (UUO) and UUO + AM group (AM). After administration of AM[10 g/ (kg x d)] for 3, 7 and 14 days,the histological changes of renal interstitial tissues were observed dynamically, and renal damage including tubular impairment and interstitial fibrosis were quantified on HE and Masson stained tissue sections. The protein expression of HGF and alpha-smooth muscle actin (alpha-SMA) was measured by immunohistochemistry. The mRNA expression of HGF and alpha-SMA were determined by real-time PCR. The expression of HGF and its receptor (C-met) were assessed by Western blot.Renal damage was exacerbated and the expression of alpha-SMA was significantly increased in UUO group compared with those of SOR group (P0.05) at each time point. HGF and C-met expression peaked at the 7th day after UUO and then decreased greatly. After AM intervention, tubular impairment and interstitial fibrosis were alleviated, up-regulations of alpha-SMA expressions was significantly suppressed, whileas the expression of HGF and C-met were significantly increased when compared with UUO group (P0. 05) at each time point.AM can ameliorate renal interstitial fibrosis induced by UUO in rats. The mechanisms of its antifibrotic effects may be related with the up-regulation of HGF and C-met expression, and the suppression of tubulo-epithelial mesenchymal transdifferentiation in renal intersitial progress.

To study the effect of Astrangalus mongholicus (AM) on the expression of Connective Tissue Growth Factor (CTGF) in SD rats with Unilateral Ureteral Obstruction (UUO) and elucidate the mechanism underlying the renorotective effects of AM.36 Sprague-Dawley rats were randomly divided into 3 groups: sham-operation group (Sham), UUO group (UUO) and UUO + AM group (AM). After administration of AM (10 g/kg x d) for 7 and 14 days, the dynamic histological changes of renal interstitial tissues were observed and renal damage including tubular impairment and interstitial fibrosis were quantified on HE and Masson stained tissue sections. The expressions of CTGF and alpha-smooth muscle actin (alpha-SMA) were measured by immunohistochemistry staining sections. The mRNA of CTGF and alpha-SMA were reversely transcribed and quantified to real-time PCR. The expression of CTGF protein was assessed by Western blot.Renal damage was exacerbated and the expressions of alpha-SMA and CTGF significantly increased in UUO group compared with those of Sham group (P0.05) at each time point. Tubular impairment and interstitial fibrosis were alleviated, and up-regulations of expressions of CTGF and alpha-SMA were significantly depressed by AM treatment (P0.05).AM can ameliorate renal interstitial fibrosis induced by UUO in rats. The mechanism of its antifibrotic effects may be related to the down-regulation of CTGF expression, following suppression of tubulo-epithelial mesenchymal transdifferentation in renal intersitial progress.

To study the effect of Astragalus mongholicus (AM) on renal interstitial fibrosis caused by unilateral ureteral obstruction (UUO) in rats in order to elucidate the mechanisms underlying the renoprotective effects of AM.54 Sprague-Dawley rats were randomly divided into 3 groups: sham-operation group (Sham), the UUO group(UUO) and UUO + AM group (AM). The rats were treated at the doses of 10 g/(kg X d) AM for 3, 7 and 14 days, the dynamic histological changes of renal interstitial tissues were observed and renal damage including tubular impairment and interstitial fibrosis were quantified on HE and Masson stained tissue sections. The expressions of transforming growth factor-beta1 (TGF-beta1) and hepatocyte growth factor (HGF) were measured by immunohistochemistry staining sections. The mRNA of HGF and TGF-beta1 were reverse transcribed and quantified by real-time PCR. The expressions of HGF and TGF-beta1 protein were assessed by Western blot.Renal damages were exacerbated and the expressions of TGF-beta1 were significantly increased in UUO group in comparison with those of Sham group (P0.05) at each time point. HGF expression increased initially and peaked at the day of 7 after UUO and then decreased greatly. The tubular impairment and interstitial fibrosis were alleviated, up-regulations of expressions of TGF-beta1 were significantly suppressed, while expressions of HGF were significantly increased in UUO + AM group in comparison with UUO group (P0.05).AM could ameliorate renal interstitial fibrosis induced by UUO in rats. The mechanisms of antifibrotic effects of AM may be associated with up-regulation of HGF expression and down-regulation of TGF-beta1 expression in renal intersitial progress.

Total saponins of Panax notoginseng (PNS) have been shown to ameliorate renal interstitial fibrosis. Ginsenoside Rg1, a panaxatriol saponin, is one of the major active molecules from PNS. The present study was undertaken to investigate the effect of ginsenoside Rg1 on renal fibrosis in rats with unilateral ureteral obstruction (UUO). The rats were randomly divided into 3 groups: sham-operation (n=15), UUO (n=15) and UUO with ginsenoside Rg1 treatment (n=15, 50 mg per kg body weight, intraperitoneally (i.p.) injected). The rats were sacrificed on Days 7 and 14 after the surgery. Histological examination demonstrated that ginsenoside Rg1 significantly inhibited interstitial fibrosis including tubular injury as well as collagen deposition. alpha-smooth muscle actin (alpha-SMA) and E-cadherin are two markers of tubular epithelial-myofibroblast transition (TEMT). Interestingly, ginsenoside Rg1 notably decreased alpha-SMA expression and simultaneously enhanced E-cadherin expression. The messenger RNA (mRNA) of transforming growth factor-beta1 (TGF-beta1), a key mediator to regulate TEMT, in the obstructed kidney increased dramatically, but was found to decrease significantly after administration of ginsenoside Rg1. Further study showed that ginsenoside Rg1 considerably decreased the levels of both active TGF-beta1 and phosphorylated Smad2 (pSmad2). Moreover, ginsenoside Rg1 substantially suppressed the expression of thrombospondin-1 (TSP-1), a cytokine which can promote the transcription of TGF-beta1 mRNA and the activation of latent TGF-beta1. These results suggest that ginsenoside Rg1 inhibits renal interstitial fibrosis in rats with UUO. The mechanism might be partly related to the blocking of TEMT via suppressing the expression of TSP-1.

To study the effect of ginsenoside Rg1 on the renal interstitial fibrosis caused by unilateral ureteral obstruction (UUO) of rats.80 healthy Sprague-Dawley rats were randomly divided into 4 groups: the UUO group (UUO), sham-operation group (SOR), ginsenoside Rg1 group (Rg1) and losartan group (ARB). From the first day after initial UUO, ARB group was intragastrically administrated with losartan 20 mg/(kg x d). UUO, Rg1 and SOR groups were intragastrically administrated with identical volume of normal saline. Rg1 group was intraperitoneally injected with ginsenoside Rg1 50 mg/(kg x d). UUO, ARB and SOR groups were intraperitoneally injected with identical volume of normal saline. At day 3, 7, 14 after UUO, 6 rats selected randomly from each group were killed. The dynamic histological changes of renal interstitial tissues were observed by HE, Masson and PAS staining. The mRNA of transforming growth factor-beta1 (TGF-beta1) was quantified by real-time PCR. The protein levels of TGF-beta1 expression were assessed by Western blot and immunohistochemical method respectively.In UUO kidneys, the interstitial fibrosis including tubular atrophy, loss and dilation, inflammatory cell infiltration and interstitial matrix deposition was prominent. However, these morphological changes were notably reduced in Rg1 and ARB groups, and there was no significant difference between the two groups (P0.05). TGF-beta1 mRNA and protein expression were increased dramatically for UUO group at postoperative day 7 and 14 (P0.05). TGF-beta1 expression in Rg1 and ARB groups were significantly lower than that in UUO group (P0.05).Ginsenoside Rg1 can evidently inhibit UUO-induced renal interstitial fibrosis in rat, which may be related to the down regulation of TGF-beta1 expression.

To evaluate and analyze relationships between states of inflammation, oxidative stress and complicatedly cardiovascular diseases in patients with maintenance hemodialysis (MHD).The analytical method for xanthine oxidase was used to measure the serum superoxide dismutase (SOD), spectrophotometry was used to measure the serum MDA, GSHPx. The immune turbidimetry was used to measure the serum levels of C-reactive protein (CRP) in patients with chronic renal failure.Compared with normal control group, the uremia groups had lower serum GSHPx, SOD and ALB levels, but higher CRP and MDA levels (P0.01). The MHD patients exhibited more serious disturbance of inflammation and oxidative stress which were aggravated as MHD time extended. CRP and MDA were significantly increased but GSHPx,SOD and ALB decreased in patients with cardiovascular events compared with the patients without them (P0.01). The results of Pearson correlation analysis showed: CRP was correlated with MDA positively (r = 0.740, P0.01), while with GSHPx, SOD, ALB negatively (r = -0.684, -0.688, -0.924, P0.01). ALB was correlated with GSHPx, SOD positively (r = 0.744, 0.728, P0.01), while with MDA negatively (r = -0 779, P0.01). The results of Logistic regression analysis showed that CRP contributed to the predictability of incidence of CVD (regression coefficient b = -1.054, Wald chi-square = 5.251, OR = 0.348, P0.05).MHD patients are in the states of inflammation and oxidative stress which are aggravated with the prolonging of hemodialysis time. Inflammation and oxidative stress may be the risk factors for occurrence of cardiovascular events.

AIM: To investigate lipopolysaccharide (LPS) related signal transduction in interstitial cells of Cajal (ICCs) from mouse small intestine. METHODS: For this study, primary culture of ICCs was prepared from the small intestine of the mouse. LPS was treated to the cells prior to measurement of the membrane currents by using whole-cell patch clamp technique. Immunocytochemistry was used to examine the expression of the proteins in ICCs. RESULTS: LPS suppressed the pacemaker currents of ICCs and this could be blocked by AH6809, a prostaglandin E2-EP2 receptor antagonist or NG-Nitro-L-arginine Methyl Ester, an inhibitor of nitric oxide (NO) synthase. Toll-like receptor 4, inducible NO synthase or cyclooxygenase-2 immunoreactivity by specific antibodies was detected on ICCs. Catalase (antioxidant agent) had no action on LPS-induced action in ICCs. LPS actions were blocked by nuclear factor κB (NF-κB) inhibitor, actinomycin D (a gene transcription inhibitor), PD 98059 (a p42/44 mitogen-activated protein kinases inhibitor) or SB 203580 [a p38 mitogen-activated protein kinases (MAPK) inhibitor]. SB 203580 also blocked the prostaglandin E2-induced action on pacemaker currents in ICCs but not NO. CONCLUSION: LPS inhibit the pacemaker currents in ICCs via prostaglandin E2- and NO-dependent mechanism through toll-like receptor 4 and suggest that MAPK and NF-κB are implicated in these actions.