It is proposed that the disease mechanism evolution of systemic lupus erythematosus can be summarized into four stages： initial invasion and latency， the pathogenesis remains concealing； latent toxin accumulation， the disease gradually becomes apparent； active toxin begins damaging， the disease manifests aggressively； damage resulting to deficiency， the disease course prolonged. Based on the stages of latent toxin evolution， the syndrome differentiation and treatment of systemic lupus erythematosus can be summarized as follows： during the initial latent stage， characterized by latent dampness and heat stagnation， modified Sanren Decoction （三仁汤） should be used； in the toxin outbreak stage， marked by intense heat toxin， modified Xijiao Dihuang Decoction （犀角地黄汤） combined with modified Qingwen Baidu Decoction （清瘟败毒饮） should be used； during the toxin damage stage， which presents as latent toxin damaging zang-fu organs， modified Qinghao Biejia Decoction （青蒿鳖甲汤） should be used； in the healthy qi deficiency stage， characterized by deficiencies of qi， blood， yin， and yang， modified Xieli Shiquan Ointment （燮理十全膏） should be used.

Cimicifugae Rhizoma (Sheng ma) is a Ranunculaceae herb belonging to a composite family and well known in China. has been widely used in traditional Chinese medicine. Thecontains three varieties ((Turcz.),L. andKom.) which have been used clinically as "Sheng-ma". However, the chemical constituents of three components of "Sheng-ma" have never been documented. In this study, a rapid method for the analysis of the main components of "Sheng-ma" was developed using ultra-high performance liquid chromatography with quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF-MS). The present study reveals the major common and distinct chemical constituents of,andand also reports principal component and statistical analyses of these results. The components were identified by comparing the retention time, accurate mass, mass spectrometric fragmentation characteristic ions and matching empirical molecular formula with that of the published compounds. A total of 32 common components and 8 markers for different "Sheng-ma" components were identified. These findings provide an important basis for the further study and clinical utilities of the three "Sheng-ma" varieties.

Objective To investigate the inhibitory effect and associated mechanism of rapamycin on proliferation and extracellular matrix (ECM) secretion in myofibroblasts stimulated by connective tissue growth factor (CTGF). Methods Primary cultivated myofibroblasts were divided into 6 groups: control, CTGF (100 μg/L), rapamycin 20 μg/L+CTGF 100 μg/L, rapamycin 40 μg/L +CTGF 100 μg/L, rapamycin 20 μg/L, and rapamycin 40 μg/L alone. 5'-bromodeoxyuridine (BrdU) incorporation assay was used to detect the myofibroblast proliferation.Western blot was used to analysis the secretory FN protein in the supernatant medium of cultured myofibroblasts and the ERK1/2 phosphorylation in myofibroblasts. Results CTGF (100 μg/L)incubation significantly increased the number of Brdu positive myofibroblasts(P<0.01) and the level of FN protein secretory (P<0.05) in cell supernatant medium compared with control group,respectively. The number of Brdu positive myofibroblasts markedly decreased by 62% and 70% (P <0.05) in rapamycin 20 μg/L+CTGF 100 μg/L and rapamycin 40 μg/L+CTGF 100 μg/L groups, respectively. The FN protein levels in supernatant were decreased by 15% and 44% compared with CTGF 100 μg/L group, respectively; but the difference of FN protein levels was significant only in rapamycin 40 μg/L group (P<0.05). CTGF could activate ERK1/2 at 10 minutes; but as myofibroblasts were pretreated with rapamycin 40 μg/L for 30 min, it abolished CTGF-induced ERK1/2 phosphoralation. PD98059, the specific inhibitor of ERK1/2, could block the effect of CTGF-induced proliferation (7%±5% vs 85%±7%, P<0.01) and FN secretion (1.0±0.1 vs 1.6±0.3, P<0.05). Conclusions Rapamycin partially suppresses the proliferation and ECM secretion of myofibroblasts induced by CTGF. Its effect may be through inhibiting CTGF-induced activation of ERKI/2 signaling pathway.

Objective To assay the expression chinse of ED1 positive cell in focal segmental glomemlosclerosis in rats,we investigated the relationship between the infiltration of mononuclear phagocytes and the progression of glomendar sclerosis.Methods We used 12 Wistar ratswhichwere dividedintotwo groups.1est group and coutrol group.Themodel offocal segmental glomerursclerosiswas ulade by in jecting PAN 9 mg/100g body weights.The rats ofcontrol group were injected 3ml 0.9％80diuln chloride.The proteinuria,serum creatinine,fipi&and protein of the rats were examined.The rata were killed at the 20th week.All the kidneys were kept and nlade into pathologic slEun-pie.1mmunohistochemical method was applied to detect the protein expression of FIN and the EDI positive cell in renal tissue of all the rats,and the number of Edl positive cell W88 counted.The results were analyzed by SPSS.Results The proteinuria of the mts in FSGS model group was significantly increased,the serum lipid ofthem was also increased.The pathology changes of the rat renal in model group showed that a part of giomemli appeared focal segmental sclerosis or all glomerular sclerosis,and the extracelhlar matrix accumulated.In the renal of model rats,the amount of EDI positive cells was significantly higher than that in normal rats(P

BACKGROUND: Angiotensin Ⅱ has been found to induce atrial electrical remodeling, which can be blocked or inhibited by allicin.OBJECTIVE: To study the effects of allicin on angiotensin Ⅱ-induced calcium channel current and intracellular free calcium concentration in human atrial myocytes.DESIGN: A randomized controlled study based on human atrial myocytes freshly isolated.SETTING: Cardiology department of a military medical university of Chinese PLA.METHODS: This study was carried out from June 2003 to June 2004 in the Laboratory of Cardiology Department, Xijing Hospital, the Fourth Military Medical University of Chinese PLA. Ten patients with congenital heart disease who underwent extracorporeal circulation surgery were included in the study. Among them, there were 6 males and 4 females with the average age of 15 ± 6 years. Tissue samples were taken from their right auricle and sent to the lab, where the atrial myocytes were freshly isolated. There were four co-administration of angiotensin Ⅱ (0. 1 μmol/L)and allicin(50 μmol/L).The conventional whole-cell configuration of the patch-clamp technique was used to detect membrane electric current of Ca2 + in L type. Confocal microscope was used with Fluo-3/AM as calcium indicator to detect changes of intracellular free calcium concentration immediately and 15 minutes after drug intervention, respectively.MAIN OUTCOME MEASURES: The peak density of electric current of Ca2 + in L type and alteration of fluoresence intensity of intracellular free calcium concentration.electric current of Ca2 + in L type in human atrial myocytes was significantly increased by angiotensin Ⅱ of 0. 1 μmol/L[( - 12. 77 ± 1. 61) vs ( -5.78affect electric current of Ca2+ in L type in human atrial myocytes group, the peak density of electric current of Ca2 + in L type was significantly lower than that in angiotensin Ⅱ group[ ( - 8.75 ± 0.97) pA/pF, P ＜ 0. 05 ].in angiotensin Ⅱ group was significantly higher than that in control and allicin groups[(2 610.1±112.6, (299.2±27.3)%; 653.9±42.5, 0;simultaneously with angiotensin Ⅱ, the alteration of intracellular fluoresence intensity was much lower than that in angiotensin Ⅱ group[ ( 1284.9 ± 85.2,(96.5±8.4)%;P ＜0.05].CONCLUSION: Allicin antagonizes angiotensin Ⅱ-induced increase in the peak density of electric current of Ca2+ in L type and intracellular calcium overload, which may relieve atrial electrical remodeling.

Objective: To investigate whether hypoxia can affect the expression and secretion of connective tissue growth factor(CTGF) and fibronectin(FN) in primary cultured rat renal cortical myofibroblasts . Methods: The primary cultured rat renal cortical myofibroblasts were subjected to hypoxic (1%O_2) or normoxic (21% O_2) conditions for a variety of times. The protein levels of HIF - 1?, CTGF and FN protein were analyzed by Western blotting in both the whole cell lysates and supernatant culture medium 6 h,12 h and 24 h after incubation, respectively. RT-PCR was carried out to measure the levels of FN mRNA at different time points (2 h,3 h,6 h and 12 h). The activity of gelatinase MMP-2 and MMP-9 in the supernatant from the cultured cell medium was assayed by gelatin zymography. Results: The expression of HIF - 1?was induced at h6 in cells under hypoxia incubation. The levels of cellular CTGF protein were increased in hypoxia treated myofibroblasts at h6 (175%?52%),significantly elevated at h12 (347%?67%,P

Objective: To address the significance of urinary podocytes in the diagnosis of human focal segmental glomerulosclerosis(FSGS). Methods: Twelve patients with FSGS and 20 patients with minimal change disease (MCD) were diagnosed by routine renal biopsy, and 8 healthy persons as controls. Morning urinary sediments was collected and centrifuged onto glass slides. Urinary podocytes were identified by immunofluorescent staining of podocyte specific protein Podocalyxin(PCX). The state of podocytes in glomeruli was observed using immunofluorescence. Results: Urinary podocytes were found in 8 out of 12 FSGS patients(66.67%), whereas none of 20 patients with MCD and control had podocytes in their urine. FSGS patients with positives urinary podocytes had prominent manifestation of nephropathy syndrome, whereas no nephrotic syndrome in patients with negative urinary podocytes. Focal absence of the expression of PCX, a marker protein of podocytes in glomeruli was found in FSGS patients, and the locations of absence were consistent with the lesions of focal sclerosis in glomeruli. In contrast, PCX was expressed integrally in MCD patients. Conclusion: Appearances of podocytes in urine of patients with nephropathy may be used as one of the reliable, convenient and unharmful accessorial methods for distinguished diagnosis of FSGS and MCD.

Objective:To observe the expression of connective tissue growth factor(CTGF) and its receptor-low density lipoprotein receptor-related protein (LRP), and the relevant signaling pathway for the regulation by long-term high glucose exposure in cultured podocytes. Methods:The effects of high glucose on the expression of CTGF and its receptor LRP were analyzed by western blotting. The activation of mitogen activated protein kinase ( MAPKS )signaling pathway by high glucose was also examined. Results: Basal levels of CTGF were observed in cultured mouse podocytes, the levels of CTGF protein were increased by high glucose medium groups on the 2nd day, reached the peak on the 4th day(P0.05).The levels of CTGF expression in normal glucose and mannitol glucose groups did not change markly. High glucose medium induced phosphorylation of ERK_ 1/2 at as early as minute 30, reached the peak at hour 6; maintained the activity at hours 12 and 24, and declined to the basal level at hour 48. However, phosphorylation of ERK_ 1/2 was not detected in normal glucose and mannitol glucose groups. Blockade of phosphorylation of ERK_ 1/2 with PD98059, a specific ERK_ 1/2 activation inhibitior, did decrease the high glucose-triggered expression of CTGF protein in 4 days. High glucose had no effect on the expression of LRP protein at each time point. Conclusion: Acute high glucose (2-4 days)stimulated the expression of CTGF protein via ERK_ 1/2-dependent signaling pathway in cultured podocytes, while cultured in high glucose for 6-8 days, the podocytes did not increase its CTGF level. Long-term high glucose had no effect on the expression of LRP in podocytes.

Objective:To investigate the anti-fibrotic effect of sirolimus(rapamycin)at the cell level.Methods:The primary cultured rat renal cortical myofibroblasts were divided into two groups,control group and sirolimus 40 mg/L group at each time point.The protein levels of ?-SMA,Col-Ⅰ,fibronectin(FN)were analyzed by Western blot in both the whole cell lysates and supernatant culture media 12 h,24 h and 48 h after incubation,respectively.Real-time quantitative PCR was carried out to measure the levels of procollagen-ⅠmRNA 1 h,2 h,4 h,and 6 h after cell incubation.The activities of gelatinase MMP-2 and MMP-9 in the supernatant from the cultured cell media were assayed by gelatin zymography.Results:(1)Sirolimus had no effect on the expression of ?-SMA of myofibroblasts at differnet time points.(2)The expression of Col-Ⅰin the whole cell lysates both reduced at the end of 24 h and 48 h in sirolimus group significantly [(0.58?0.05)and(0.63?0.18),P

Objective: To investigate peroxisome proliferator activated receptor ? (PPAR ?) expressions in patients with actively proliferating glomerulonephritis such as type Ⅳ lupus nephritis (LN) and cellular crescentic glomerulonephritis (RPGN). Methods: All patients were divided into 4 groups as follows: RPGN (17 cases); LN type Ⅳ (15 cases); mild mesangial proliferative IgA nephropathy (IgAN, 7 cases) and minimal change disease (MCD, 10 cases). Clinical parameters, immunohisto chemistry stain and in situ hybridization of renal biopsy specimens were performed. Results: Clinically, proteinuria and hematouria were increased and Ccr were decreased in LN and RPGN patients, and increased ESR and decreased complement C3 were found in group LN. Active index of renal specimens were significantly higher in LN and RPGN groups than in IgAN and MCD groups. Renal specimens of MCD patients showed no positive PPAR ? staining in all sections; little immunoreactivity was detected in sections of glomerular, tubular and interstitial cells from IgAN patients. Glomerular positive staining of PPAR ? in renal sections in LN and RPGN patients[(3.3?1.8) and (2.8?1.2) cells per section of glomerulus, respectively] were significantly increased compared with that in IgAN patients [(0.7?0.5) cells per section of glomerulus]. Similarly, tubular positive staining of PPAR ? in LN and RPGN patients (27.38? 12.46, 23.36?10.55) were also elevated compared with that in IgAN and MCD patients(6.51?3.49, 1.72?0.31). The relevance assay results showed positive relationship between active index and glomerular or tubular PPAR ? immunohisto chemistry staining cell numbers (0.478, P