Practice and exploration of formative assessment in diagnostics teaching / 中华医学教育探索杂志

Objective:To explore the method of building the formative assessment (FA) system in diagnostics teaching and investigate its implementation effect.Methods:We planned and formulated the formative assessment system in diagnostics teaching of undergraduate curriculum. The correlation between the scores of the formative assessment and final exam were analyzed. A questionnaire survey on students' attitudes towards FA and an interview on teachers' perspectives were conducted. SPSS 17.0 was used for statistical analysis. Linear correlation analysis was used to compare the final exam scores with formative assessment scores, and Wilcoxon rank sum test was used to compare the scores of questionnaire items.Results:The scores of FA were significantly positive related to the scores of final exam ( r = 0.559, P < 0.001). The questionnaire analysis showed that students significantly valued the formative assessment superior to the summative assessment ( Z = -8.632, P<0.001). It was generally approved of the promotion of FA in students' self-direct learning and self-supervision and the advances in acquirement of knowledge and skills. Conclusion:It is feasible of carrying FA in diagnostics teaching which could provide better learning outcome and might have an extensive prospect of application.

Influence of Hip Joint Flexion Angle on the Submerged Dolphin Kick Stroke Based on Numerical Simulation of Multi-Body Motion / 医用生物力学

Objective To explore characteristics of flow field around the athletes, change of net flow force, and influences of hip flexion angles at the end of extension kick on the submerged dolphin kick stroke. Methods The body shape data of a swimmer were obtained by three-dimensional (3D) scanning, and the data were reversely reconstructed to obtain the swimmer model. The joints of the swimmer model were separated, and each segment of the athlete was divided into independent rigid body, and simulation of the submerged dolphin kick stroke was realized by controlling movement of each independent rigid body. The computational fluid dynamics (CFD) software package ANSYS Fluent was used as the solver for calculation and solution. Results The vortex structures were shed off from the surface of the swimmer’s body in the area with a large velocity gradient in flow field, and the shedding of vortex structures was different at the stage of extension kick and flexion kick. Propulsion was mainly generated during extension kick phase. At the end of extension kick, the drag decreased as the hip flexion angle increased from 20° to 30°. Conclusions To some extent, increasing flexion angle of the hip joint at the end of extension kick will reduce the drag force and increase the swimming speed in process of the submerged dolphin kick stroke.

Application of bilingual mixed grouping in ward round teaching for overseas students in cardiology department / 中华医学教育探索杂志

Due to the problems of language barriers and cultural differences existing in the current clinical practice teaching activities of overseas students, this study proposes to divide the oversea students and Chinese students into bilingual mixed groups in the ward rounds teaching. Through the selection of typical cases and the application of flipped classroom, the Chinese and English versions of learning materials related to disease are provided to the interns for learning in advance, and the oversea students and Chinese students are requested to complete the history and auxiliary examination data collection in Chinese and English in cooperation, and then the teacher leads the group to carry out ward rounds teaching, including bedside English history report, physical examination, case analysis, discussion and summary, so as to improve the participation enthusiasm of overseas students and also improve the teaching effects.

The application of team-based learning in gastroenterological clinical teaching / 中华医学教育探索杂志

Objective To compare the learning outcomes of team-based learning (TBL) and traditional pedagogy in gastroenterological clinical teaching.Methods Sixty students on eight-year program of clinical medicine were randomly divided into TBL group and tradition group.The two groups adopted TBL and traditional pedagogy respectively in gastroenterological clinical teaching.The scores for Individual Readiness Assurance Test-baseline (IRAT-baseline),Group Readiness Assurance Test (GRAT) and Individual Terminal Test (ITT) in TBL group were compared.The scores for IRAT-baseline,ITT and clinical practice in TBL group were contrasted with those in tradition group.Besides,students in TBL group were investigated by questionnaire after the experiment.Results Compared with tradition group,TBL group spent more time on self-study before clinical teaching [(85.70 ± 11.43) vs.(35.00 ± 9.47),P=0.000].In addition,the form of self-study was more diversified in TBL group than that in tradition group.Students in TBL group achieved higher scores in IRAT-baseline [(17.78 ±5.07) vs.(12.57±4.26),P=0.000],ITT [(23.66 ±5.36) vs.(18.52 ± 4.54),P=0.000] and clinical practice test [(16.53 ± 5.10) vs.(12.24 ± 4.59),P=0.001] when contrasted to tradition group.TBL group gained higher scores in GRAT than those in IRAT-baseline [(27.82 ± 3.12) vs.(17.78 ± 5.07),P=0.000].After the teaching intervention,the scores for ITT were higher than those for IRAT-baseline in both TBL group and tradition group [(23.66 ± 5.36) vs.(17.78 ± 5.07),P=0.000;(18.52 ± 4.54) vs.(12.57 ± 4.26),P=0.000].However,there was no statistical difference in the growth of scores from IRAT-baseline to ITT between TBL group and tradition group [(5.69 ± 2.76) vs.(5.36 ± 2.00),P=0.754].The result of the questionnaire showed that a majority of students in TBL group (＞70％) approved of "I was actively involved in TBL" "TBL is helpful for self-study I've benefited from teacher's explanation in TBL" "I have benefited from group discussion in TBL" and "TBL is more attractive than the traditional pedagogy".Nevertheless,more than half of students in TBL group also indicated "Knowledge learned in TBL is more fragmented than that in traditional pedagogy" and "TBL increased my course load".Conclusions TBL contributes to improving abilities of autonomous learning,clinical thinking,teamwork,communication and knowledge application.This teaching mode could arouse students' learning interests and enhance clinical teaching outcomes.TBL is worth popularizing in gastroenterological clinical teaching.

Controlled clinical study on compound Decumbent Corydalis Rhizome and diclofenac in treatment of knee osteoarthritis / 中国中药杂志

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 (P < 0.05). In the controlled study, compound DCR is as efficient as diclofenac sodium but more tolerable, with a good clinical application prospect.

Endogenous hydrogen sulfide and androgen deficiency-induced erectile dysfunction in rats / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the role of endogenous hydrogen sulfide (H2S) in erectile dysfunction (ED) induced by androgen deficiency.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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) (P <0.05), 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) (P <0. 05) , and so were ICP/MAP after 5 and 7 V electrical stimulation of the pelvic ganglia (P <0. 05) , H2 S concentration (P <0.05), and the expressions of CBS and CSE (P <0.05). The expressions of CBS and CSE proteins were also significantly decreased in group C as compared with D (P <0.05).</p><p><b>CONCLUSION</b>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.</p>

Interplay of Hydrogen Sulfide and Nitric Oxide on the Pacemaker Activity of Interstitial Cells of Cajal from Mouse Small Intestine / 전남의대학술지

We studied whether nitric oxide (NO) and hydrogen sulfide (H2S) have an interaction on the pacemaker activities of interstitial cells of Cajal (ICC) from the mouse small intestine. The actions of NO and H2S on pacemaker activities were investigated by using the whole-cell patch-clamp technique and intracellular Ca2+ analysis at 30degrees C in cultured mouse ICC. Exogenously applied (+/-)-S-nitroso-N-acetylpenicillamine (SNAP), an NO donor, or sodium hydrogen sulfide (NaHS), a donor of H2S, showed no influence on pacemaker activity (potentials and currents) in ICC at low concentrations (10 microM SNAP and 100 microM NaHS), but SNAP or NaHS completely inhibited pacemaker amplitude and pacemaker frequency with increases in the resting currents in the outward direction at high concentrations (SNAP 100 microM and NaHS 1 mM). Co-treatment with 10 microM SNAP plus 100 microM NaHS also inhibited pacemaker amplitude and pacemaker frequency with increases in the resting currents in the outward direction. ODQ, a guanylate cyclase inhibitor, or glibenclamide, an ATP-sensitive K+ channel inhibitor, blocked the SNAP+NaHS-induced inhibition of pacemaker currents in ICC. Also, we found that SNAP+NaHS inhibited the spontaneous intracellular Ca2+ ([Ca2+]i) oscillations in cultured ICC. In conclusion, this study describes the enhanced inhibitory effects of NO plus H2S on ICC in the mouse small intestine. NO+H2S inhibited the pacemaker activity of ICC by modulating intracellular Ca2+. These results may be evidence of a physiological interaction of NO and H2S in ICC for modulating gastrointestinal motility.

Interplay of Hydrogen Sulfide and Nitric Oxide on the Pacemaker Activity of Interstitial Cells of Cajal from Mouse Small Intestine / 전남의대학술지

We studied whether nitric oxide (NO) and hydrogen sulfide (H2S) have an interaction on the pacemaker activities of interstitial cells of Cajal (ICC) from the mouse small intestine. The actions of NO and H2S on pacemaker activities were investigated by using the whole-cell patch-clamp technique and intracellular Ca2+ analysis at 30degrees C in cultured mouse ICC. Exogenously applied (+/-)-S-nitroso-N-acetylpenicillamine (SNAP), an NO donor, or sodium hydrogen sulfide (NaHS), a donor of H2S, showed no influence on pacemaker activity (potentials and currents) in ICC at low concentrations (10 microM SNAP and 100 microM NaHS), but SNAP or NaHS completely inhibited pacemaker amplitude and pacemaker frequency with increases in the resting currents in the outward direction at high concentrations (SNAP 100 microM and NaHS 1 mM). Co-treatment with 10 microM SNAP plus 100 microM NaHS also inhibited pacemaker amplitude and pacemaker frequency with increases in the resting currents in the outward direction. ODQ, a guanylate cyclase inhibitor, or glibenclamide, an ATP-sensitive K+ channel inhibitor, blocked the SNAP+NaHS-induced inhibition of pacemaker currents in ICC. Also, we found that SNAP+NaHS inhibited the spontaneous intracellular Ca2+ ([Ca2+]i) oscillations in cultured ICC. In conclusion, this study describes the enhanced inhibitory effects of NO plus H2S on ICC in the mouse small intestine. NO+H2S inhibited the pacemaker activity of ICC by modulating intracellular Ca2+. These results may be evidence of a physiological interaction of NO and H2S in ICC for modulating gastrointestinal motility.

5-Hydroxytryptamine Generates Tonic Inward Currents on Pacemaker Activity of Interstitial Cells of Cajal from Mouse Small Intestine

In this study we determined whether or not 5-hydroxytryptamine (5-HT) has an effect on the pacemaker activities of interstitial cells of Cajal (ICC) from the mouse small intestine. The actions of 5-HT on pacemaker activities were investigated using a whole-cell patch-clamp technique, intracellular Ca2+ ([Ca2+]i) analysis, and RT-PCR in ICC. Exogenously-treated 5-HT showed tonic inward currents on pacemaker currents in ICC under the voltage-clamp mode in a dose-dependent manner. Based on RT-PCR results, we found the existence of 5-HT2B, 3, 4, and 7 receptors in ICC. However, SDZ 205557 (a 5-HT4 receptor antagonist), SB 269970 (a 5-HT7 receptor antagonist), 3-tropanylindole - 3 - carboxylate methiodide (3-TCM; a 5-HT3 antagonist) blocked the 5-HT-induced action on pacemaker activity, but not SB 204741 (a 5-HT2B receptor antagonist). Based on [Ca2+]i analysis, we found that 5-HT increased the intensity of [Ca2+]i. The treatment of PD 98059 or JNK II inhibitor blocked the 5-HT-induced action on pacemaker activity of ICC, but not SB 203580. In summary, these results suggest that 5-HT can modulate pacemaker activity through 5-HT3, 4, and 7 receptors via [Ca2+]i mobilization and regulation of mitogen-activated protein kinases.

Capsaicin Inhibits the Spontaneous Pacemaker Activity in Interstitial Cells of Cajal From the Small Intestine of Mouse

BACKGROUND/AIMS: Capsaicin (8-methyl-N-vanillyl-6-ninenamide), a compound found in hot peppers, has been reported to have different physiological actions on different cell types. Not much work has been done about the effect of capsaicin on the function of interstitial cells of Cajal (ICC). In the present study, we examined the action of external application of capsaicin on pacemaker activity in the cultured ICC from the small intestine of mouse. METHODS: We investigated the effect of capsaicin on pacemaker currents in cultured ICC from the small intestine of mouse using a whole cell patch-clamp technique and Ca2+-imaging analysis. RESULTS: When capsaicin was applied externally to the pacemaker generating ICC, it completely inhibited the pacemaker potential under current-clamp mode (I = 0) and the pacemaker current under voltage-clamp mode at a -70 mV of holding potentials. The effect of capsaicin on pacemaker activity in ICC was shown dose dependently. The effect of capsaicin was not through the transient receptor potential of the vanilloid type 1 (TRPV1) channel as capsazepine did not block the effect of capsaicin. L-NAME, an inhibitor of nitric oxide synthase, also did not block the capsaicin-induced effects. When the action of capsaicin was examined in the intracellular calcium oscillation, it completely abolished the calcium oscillation. CONCLUSIONS: These results prove that the capsaicin has the inhibitory effects on the ICC which is carried out neither through TRPV channel nor the nitric oxide production. Intracellular Ca2+ was also an important target for actions of capsaicin on ICC.

Effects of ginsenoside Rg1 on streptozocin-induced diabetic nephropathy in rats / 生物医学工程学杂志

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 (P < 0.05). 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.

Clinical efficacy of Corydalis composite combined with methotrexate in treating rheumatoid arthritis / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the clinical efficacy and safety of Corydalis composite (CDC) combined with methotrexate (MTX) in treating rheumatoid arthritis (RA).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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 (P < 0.05). 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%, P < 0.05). As compared with the control group, the improvements in all the auxiliary criteria were more significant in the treated group (P < 0.05). The incidence of adverse reaction was less in the treated group than in the control group (32.43% vs. 56.41%, P < 0.05), particularly in term of the damage on liver (0 vs. 10.26%, P < 0.05).</p><p><b>CONCLUSION</b>CDC combined with MTX is more effective than MTX alone in treating active RA with less adverse reaction.</p>

Effect of Astragalus mongholicus on expression of transforming growth factor- beta1 in SD rats with unilateral ureteral occlusion / 中国中药杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHOD</b>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.</p><p><b>RESULT</b>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 (P<0.05) 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 (P<0.05).</p><p><b>CONCLUSION</b>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.</p>

Ginsenoside Rb1, a panoxadiol saponin against oxidative damage and renal interstitial fibrosis in rats with unilateral ureteral obstruction / 中国结合医学杂志

<p><b>OBJECTIVE</b>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).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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 (P<0.05). 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 (P<0.05). Ginsenoside Rb1 also inhibited the heme oxygenase (HO-1) and 8-OHdG, two markers of oxidative stress (P<0.05). Moreover, ginsenoside Rb1 suppressed the expression of p47phox, a subunit of nicotinamide adeninedinucleotide phosphate (NADPH) oxidase (P<0.05).</p><p><b>CONCLUSION</b>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.</p>

Influence of ginsenoside Rg1, a panaxatriol saponin from Panax notoginseng, on renal fibrosis in rats with unilateral ureteral obstruction / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

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.

Effect of sodium ferulate on transdifferentiation and extracellular matrix of rat renal tubular epithelial cells induced by transforming growth factor beta 1 / 中国组织工程研究

BACKGROUND: Renal tubulointerstitial fibrosis is mainly featured as the accumulation of extracellular matrix (ECM) in renal interstitium. The tubular epithelial-myofibroblast transdifferentiation (TEMT) is important to the pathogenesy of renal tubulointerstitial fibrosis. OBJECTIVE: To examine the effects of sodium ferulate (SF) on TEMT, and ECM main components such as collagen Ⅰ, collagen Ⅲ and fibronectin, in rat renal tubular epithelial cellsinduced by transforming growth factor-beta 1 (TGF- β1)- DESIGN: Randomized and controlled experimental study based on cells. SETTING: Department of Kidney in West China Hospital of Sichuan University. MATERIALS: Rat renal tubular epithelial cells (NRK-52E) originated from American Type Culture Collection (ATCC), were offered by the laboratory of Department of Nephrology in Australian Monash Medical Center. Cell strain used in this study was cultured at the 36th passage. SF white crystal with water solubility and more than 98.0% purify, was from Chengdu Hengda Pharmaceutical Co., Ltd. Different concentrations of SF (125,250, 500μreel/L) were designed in this study. Rabbit anti-rat α-smooth muscle actin (α -SMA) was produced by Wuhan Boster Company. Enzyme-linked immunosorbent assay (ELISA) kit was the produced of Shanghai Senxiong Science and Technology Co.,Ltd. Human recombinant TGF- β1 was produced by R&D Company. DNA Engine OpticonTM real-time fluorescence quantitative polymerase chain reaction apparatus was the product of MJ Research Company. METHODS: Rat renal tubular epithelial cells (NRK-52E) cultured in vitro were divided into five groups. Control group was added with serum-contained DMEM; TGF-β1-induced group was added with TGF-β1 at final concentration of 5 ng/L; SF at different concentrations groups were added with 125, 250, 500 μ mol/L SF and TGF- β1 at final concentration of 5 ng/L,respectively. MAIN OUTCOME MEASURES: The contrast phase microscope, real-time fluorescence quantitative polymerase chain reaction and ELISA method were used to detect TEMT of NRK52E cells induced by TGF-β1 and levels of collagen Ⅰ, collagen Ⅲ and fibronectin in the supernatant. RESULTS: Morphology of NRK52E cells: Compared with control group, TGF-β1 could induce the transdifferentiation of NRK52E cells, showing fibroblast-like in morphology after 3 days, which were previously the typical road stone-like epithelial cells. In three different concentration SF groups, the morphologic transformation stimulated by TGF-β1 could be partly ameliorated in a dose-dependent manner. Expression of α-SMA mRNA: Compared with control group, 5 ng/L TGF- β1 enhanced expression of α-SMA at 6 hours, and reached a peak at 72 hours; SF depressed the expression in a dose-dependent manner at 72 hours (P < 0.05). Changes of ECM: After induced by 5 ng/L TGF- β1 for 72 hours, the levels of collagen Ⅰ, collagen Ⅲ and fibronectin in the supernatant increased significantly (P < 0.05), whereas SF decreased these levels in a dose-dependent manner (P < 0.05). CONCLUSION: TGF- β1 induces the TEMT, and promotes the secretion of collagen Ⅰ, collagen Ⅲ and fibronectin. SF can inhibit TGF- β1-induced TEMT In a dose-dependent manner.

Expression of connective tissue growth factor following Sodium Ferulate in rats with unilateral ureteral obstruction / 中国组织工程研究

BACKGROUND: Connective tissue growth factor (CTGF) is a kind of factor that can mediate downstream action of transforming growth factor-β 1 (TGF- β 1). The upregulation of connective tissue growth factor expression plays an important role in pathological changes of renal interstitial fibrosis.OBJECTIVE: To explore the effect of Sodium Ferulate on the expression of CTGF mRNA and protein in rats with unilateral ureteral obstruction (UUO) and pathological changes of renal interstitial fibrosis, and to compare with Losartan.DESIGN: Randomized and controlled animal trial.SETTING: Department of Nephrology, West China Hospital of Sichuan University, and College of Public Health, Sichuan University.MATERIALS: Twenty-four healthy adult male SD rats were selected from the Experimental Animal Center of Sichuan University. Sodium Ferulate was provided by Sichuan Hengda Pharmacy Co, Ltd (No. 050302); rabbit anti-rat CTGF by Santa Cruz; Western blotting by BioRAD, USA; DNA Engine OpticonTM real-time fluorescent quantitation PCR device by MJ Research, USA.METHODS: The experiment was performed at Research Laboratory of Clinical Medicine (grade BSL-1), College of Public Health, Sichuan University from May to December 2006. Twenty-four healthy rats were randomly divided into 4 groups (n=6): UUO model group, Sodium Ferulate group, Losartan group, and sham-operation group. According to the previous protocol, UUO models were established in UUO model group, Sodium Ferulate group, and Losartan group, and the other rats were subjected to sham operation. From the first day after UUO, Sodium Ferulate group was intragastrically (i.g.)administrated with 150 mg/kg/d Sodium Ferulate; Losartan group was administrated ig. with 20 mg/kg/d. Losartan; UUO and sham operation groups were administrated i.g. with matching normal saline. All rats were executed 14 days after UUO to harvest partial renal tissues. All experimental procedure was accorded with animal ethical standards.MAIN OUTCOME MEASURES: The mRNA and protein expressions of CTGF were quantified by real-time PCR and Western blot. The pathological changes of renal interstitial tissues were observed by hematoxylin/eosin (HE) and Masson staining.RESULTS: Twenty-four rats were included in final analysis. Fourteen days after UUO, CTGF mRNA and protein expressions in UUO model group were significantly increased compared with sham operation group, but the expressions in Sodium Ferulate group were significantly lower than model group (P < 0.05). Compared with Losartan treated group, there was no significant difference (P > 0.05). HE and Masson staining showed inflammatory cell infiltration and tubular and interstitial changes as well as collagen deposition in renal interstitial tissues on day 14 after UUO. Sodium Ferulate obviously improved the renal pathological changes in UUO rats (P < 0.05), and the effect was similar to Losartan (P > 0.05).CONCLUSION: Sodium Ferulate inhibits UUO-induced renal interstitial fibrosis. This action, similar to the effect of Losartan, might be due to downregulation of CTGF expression.

(-)-Epigallocatechin Gallate Inhibits the Pacemaker Activity of Interstitial Cells of Cajal of Mouse Small Intestine

The effects of (-)-epigallocatechin gallate (EGCG) on pacemaker activities of cultured interstitial cells of Cajal (ICC) from murine small intestine were investigated using whole-cell patch-clamp technique at 30degrees C and Ca2+ image analysis. ICC generated spontaneous pacemaker currents at a holding potential of -70 mV. The treatment of ICC with EGCG resulted in a dose-dependent decrease in the frequency and amplitude of pacemaker currents. SQ-22536, an adenylate cyclase inhibitor, and ODQ, a guanylate cyclase inhibitor, did not inhibit the effects of EGCG. EGCG-induced effects on pacemaker currents were not inhibited by glibenclamide, an ATP-sensitive K+ channel blocker and TEA, a Ca2+-activated K+ channel blocker. Also, we found that EGCG inhibited the spontaneous [Ca2+]i oscillations in cultured ICC. In conclusion, EGCG inhibited the pacemaker activity of ICC and reduced [Ca2+]i oscillations by cAMP-, cGMP-, ATP-sensitive K+channel-independent manner.

Ameliorative effects of 99Tc-methylene diphosphonate on the articular gall symptoms in patients with rheumatoid arthritis / 中国组织工程研究

BACKGROUND: It is always the key issue of rheumatoid arthritis(RA) to treat articular gall. A kind of medicine with favorable therapeutic effects and safety is urgently needed in the clinics. 99Tc-methylene diphosphonate 99(Tc-MDP) receives generalized attentions on its therapeutic effects and safety since its application into RA therapy.OBJECTIVE: To explore the characters of 99Tc-MDP in the amelioration of articular dysfunction in RA patients.DESIGN: A before-and-after controlled study by employing patients as subjects.SETTING: Department of rheumatism and immunology of an affiliated hospital of a university.PARTICIPANTS: Totally 67 patients with RA at active phase including 11males and 56 females aged between 29 and 71 years old with the course of disease between 9 and 78 months and admitted by the Department of Rheumatism of Huaxi Hospital Affiliated to Sichuan University were in accordance with the RA diagnostic criteria established by American Rheumatism Association(ARA) in 1987. Serious heart,liver or kidney dysfunction,active gastrointestinal pathological changes, hematology and endocrinology diseases,allergic complexion,and women during pregnancy or breast-feeding period were eliminated.METHODS: Clinical indicators including articular edema index, articular pain,grip,morning stiffness duration,rest pain,erythrocyte sedimentation rate (ESR) and C reactive protein(CRP) were compared before and after therapy in 67 cases received 99Tc-MDP treatment. Integrated evaluation was performed after the completion of therapy. Effective meant 30% of improvement in symptoms and physical signs,and reduction in ESR and CRP. Side effects were observed and recorded simultaneously. Data were statistically analyzed.RESULTS: After 99Tc-MDP treatment,RA condition significantly improved,as well as each clinical indicator including articular edema index,articular pain index,morning stiffness duration,rest pain,ESR and CRP(P<0.05) . The total clinical effective rate of this medicine was 81% and the incidence of side effects was small and mild.CONCLUSION: 99Tc-MDP can ameliorate the articular dysfunction of RApatients,which is a safe medicine with strong effect.

Clinical application in the therapy of rheumatoid arthritis with Technetium ~(99m)Tc methylenediphosphona-te injection / 中华风湿病学杂志

Objective To investigate the efficacy and safety of Technetium 99m Tc methylenediphos-phonate injection (Yunke) and various combination therapy on rheumatoid arthritis.Methods All 137 patients enrolled in trial group.Among them 67 patients received Technetium 99m Tc methylenediphosphonate alone,42 patients received combination therapy with methotrexate and mobik and 28 patients received calcium orally meanwhile.Clinical manifestations and lab markers were observed carefully.Results The conditions of 67 patients receiving Technetium 99m Tc methylenediphosphonate alone were improved,42 patients received combination therapy had better effect and 28 patients in middle and old-age taking calcium orally simultaneously showed superiority in remission of rest pain and descent of ESR.Conclusion Technetium 99m Tc methylenediphosphonate is an effective and safe drug in the treatment of rheumatoid arthritis.Results is suggest calcium be taken in the same time.