Effect of Ca2+/calmodulin-dependent protein kinaseⅡinhibitor KN-93 on late sodium current in rabbits model of heart failure / 中国病理生理杂志

AIM:To investigate the change of late sodium current (INaL) and the effect of Ca2+/calmodulin-dependent protein kinaseⅡ (CaMKⅡ) inhibitor KN-93 on INaLin the cardiomyocytes after isoproterenol-induced heart fai-lure (HF) in rabbits. METHODS:The rabbit model of HF was induced by injecting isoproterenol (300 μg·kg-1· d-1) for 15 d. One month later, all rabbits received by echocardiography and HE staining to observe the morphological changes of myocardium for evaluating the HF model. The protein expression of NaV1.5, CaMKⅡδ and phosphorylated CaMKⅡδ was determined by Western blot. The ventricular myocytes were isolated from the rabbits of normal saline(NS) group and HF group by Langendorff perfusion, and the whole-cell patch-clamp technique was used to record INaL. RE-SULTS:Compared with NS group,the heart rate in HF group was increased (P<0.01), the ventricular cavity was en-larged (P<0.05),and the cardiac function was decreased(P<0.01). Compared with NS group,the cardiomyocytes in HF group arranged in disorder, vacuolar degeneration and myocardial interstitial edema were observed, and fibrous tissue increased. The protein levels of NaV1.5,CaMKⅡδ and phosphorylated CaMKⅡδ in HF group were higher than those in NS group(P<0.01). INaLin HF group significantly increased compared with NS group (P<0.01). After adding sea anemone toxin Ⅱ (ATXⅡ), the density of INaLin HF group and NS group was significantly increased, but that in HF group increased more obviously than that in NS group (P<0.01). After ATXⅡ had induced stable current, we added KN-93 into NS group and HF group,and we found that the ATXⅡ-increased INaLin NS group and HF group was signifi-cantly decreased(P<0.05).CONCLUSION:CaMKⅡinhibitor KN-93 inhibits the increase in INaLin HF rabbits,which may be related to the activity of CaMKⅡδ and the regulation of CaMKⅡ δ on INaL.

Simultaneous purification of shikimic acid and total flavonoids from pine needles of Cedrus deodara by macroporous adsorption resin / 中草药

Objective: To research the simultaneous purification process of shikimic acid and total flavonoids from pine needles of Cedrus deodara (Roxb.) G. Don. Methods: Taking the purity of shikimic acid and total flavonoids as the evaluation indicator, the purification effect of six macroporous resins were evaluated. Orthogonal design L9(34) and single factor experiments were employed to optimize the purification conditions by comprehensive scoring. The purification capacity of the best resin was investigated by the sample mass concentration, the volume flow of the sample, the ratio of the resin to the drug, the amount of water for washing, the concentration of ethanol, and the elution of ethanol. Results: XAD 7HP macrophous resin offered better purification effect of shikimic acid and total flavonoids from pine needles of C. deodara than other macrophous resins. The optimum purification condition was confirmed as follows: The concentration of shikimic acid in the sample was 11.59 mg/mL, and total flavonoids concentration was 6.9 mg/mL; The flow rate was 8 BV/h, and the sample volume was 2.0 mL/g; The shikimic acid was eluted with loading capacity and 4 BV of water; The total flavonoids was eluted with 4 BV of 70% ethanol successively. The purity of shikimic acid can be increased from 19.25% to 28.98%, and the purity of total flavonoids can be increased from 11.92% to 54.45%. Conclusion: The optimized purification process is stable, feasible and suitable for pilot enrichment of shikimic acid and total flavonoids from pine needles of C. deodara.

Anti-aging traditional Chinese medicine： potential mechanisms involving AMPK pathway and calorie restriction based on "medicine-food homology" theory / 中国中药杂志

There have been many reports about the anti-aging effect of traditional Chinese medicine (TCM), but the material basis and mechanism of action have not been clearly elucidated. AMP-activated protein kinase (AMPK) is the receptor of energy metabolism and its life extending effect has been confirmed in different experiments. Over expression or activation with metform in of AAK-2/AMPK has been shown to extend life expectancy in nematodes and Drosophila. The possible downstream pathways of AMPK against aging include TOR/S6k pathway, FOXOs pathway and CRTC pathway. One of the core concepts of traditional Chinese medicine is disease prevention, for which one of manifestations is to improve the body with the same source of medicine and food to achieve longevity. It is possible to activate AMPK to achieve the goal of health preservation and prolonging the life by some of the "medicine-food harmony" treatments. Our survey finds that in "medicine-food harmony" compound TCM, "invigorating the kidney deficiency and promoting blood circulation" class dominates and Salviae Miltiorrhizae Radix Rhizoma, Astragali Radix, Coptidis Rhizoma, Poria, Atractylodes Macrocephalae Rhizoma, Radix et Rhizoma Rhei, and Ginseng Radix et Rhizoma are used in high frequency. Network pharmacology analysis using ingenuity pathway analysis (IPA) software revealed that TCM-derived drugs interacting with AMPK target proteins included berberine, emodin, curcumin, resveratrol, alcohol, cordyceps, arctiin, suggesting in a certain extent the feasibility of "medicine -food homology" drugs to extend the lifespan through the AMPK pathway. Our study combines a comprehensive database query and an IPA network pharmacology analysis to identify Chinese medicine monomer and components that may activate AMPK pathway to delay aging and to discuss the potential of these medicine by improving energy metabolism to delay the aging process, based on the concept of traditional Chinese medicine "medicine-food homology".

Reduction of the amount of intestinal secretory IgA in fulminant hepatic failure

Intestinal barrier dysfunction plays an important role in spontaneous bacterial peritonitis. In the present study, changes in the intestinal barrier with regard to levels of secretory immunoglobulin A (SIgA) and its components were studied in fulminant hepatic failure (FHF). Immunohistochemistry and double immunofluorescent staining were used to detect intestinal IgA, the secretory component (SC) and SIgA in patients with FHF (20 patients) and in an animal model with FHF (120 mice). Real-time PCR was used to detect intestinal SC mRNA in the animal model with FHF. Intestinal SIgA, IgA, and SC staining in patients with FHF was significantly weaker than in the normal control group (30 patients). Intestinal IgA and SC staining was significantly weaker in the animal model with FHF than in the control groups (normal saline: 30 mice; lipopolysaccharide: 50 mice; D-galactosamine: 50 mice; FHF: 120 mice). SC mRNA of the animal model with FHF at 2, 6, and 9 h after injection was 0.4 ± 0.02, 0.3 ± 0.01, 0.09 ± 0.01, respectively. SC mRNA of the animal model with FHF was significantly decreased compared to the normal saline group (1.0 ± 0.02) and lipopolysaccharide group (0.89 ± 0.01). The decrease in intestinal SIgA and SC induced failure of the intestinal immunologic barrier and the attenuation of gut immunity in the presence of FHF.

Chemical constituents of flavonoids in pine needles of Cedrus deodara / 中草药

Objective: To study the chemical constituents of flavonoids in the pine needles of Cedrus deodara. Methods: Flavonoids were isolated and purified from ethyl acetate extract of the pine needles by chromatography on silica gel and Sephadex LH-20. Their structures were identified on the basis of spectroscopic analysis and chemical evidence. Results: Five flavonoids were isolated and identified as 3′,5′-dimethoxymyricetin-3-O-(6″-O-acetyl)- α-D-glucopyranoside (1), myricetin (2), 2R,3R-dihydromyricetin (3), quercetin (4), and 2R,3R-dihydroquercetin (5). Conclusion: Compound 1 is a new compound named as cedrusone A. Compounds 2-5 are isolated from the pine needles in the plants of Cedrus Trew for the first time.

Glomerular disease associated with Takayasu arteritis: 6 cases analysis and review of the literature / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the clinical features, renal histopathology and therapeutic response to glucocorticoid and immunosuppressive agents in patients with glomerular disease associated with Takayasu arteritis (TA).</p><p><b>METHODS</b>Patients with TA and renal biopsy-confirmed glomerular disease were investigated retrospectively. None of them had renal artery stenosis or occlusive changes.</p><p><b>RESULTS</b>Six patients with glomerulopathy, accounting for 3.75% of the 160 TA patients admitted to our hospital at the same period, were analyzed. All of them were females with a mean age of 35.5 +/- 10.0 years. Four cases presented with lower extremity edema. Laboratory tests showed that one was nephrotic syndrome, three were nephrotic range proteinuria, and two of them had mild renal dysfunction. The other two patients were asymptomatic microscopic hematuria and proteinuria. Renal pathology revealed mild immunoglobulin A nephropathy in two cases, mild mesangial proliferative glomerulonephritis (GN), membranoproliferative GN, minimal change disease, and fibrillary GN in one case respectively. Five cases received glucocorticoids and cyclophosphamide therapy. Proteinuria and microscopic hematuria disappeared in 2 to 4 weeks after the initiation of therapy in three cases. The patient with membranoproliferative GN also reached complete remission of proteinuria and recovered renal function 6 months after the treatment.</p><p><b>CONCLUSIONS</b>TA may induce glomerular disease as a part of its histological spectrum. Apart from ischemic glomerular disease, glomerular disease should be suspected when TA patients have microscopic hematuria or proteinuria, that may be therapeutically responsive to glucocorticoids and immunosuppressive agent in relative early phase.</p>

Brain-derived neurotrophic factor and neural stem cells transplantation in treatment of hypoxic-ischemic brain injury in rats / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the effects of brain-derived neurotrophic factor (BDNF) on survival, migration and differentiation of neural stem cells (NSCs) transplanted into the brain of newborn rats with hypoxic-ischemic brain damage and the recovery of nervous functions.</p><p><b>METHODS</b>The NSCs were separated from hippocampus of neonatal Wistar rats within 24 h after birth. Brdu, NSE and GFAP were used as markers of differentiation and proliferation of NSCs. The newborn rats were subjected to hypoxic-ischemic condition to induce brain damage. Seven days later, NSCs transplantation was performed for the animals. The rats were divided into normal control group, HIBD group, PBS group, NSCs transplantation group, BDNF group and BDNF + NSCs transplantation group randomly. At 4 weeks after transplantation the nervous function of rats was observed by Y-maze and nerve behavior test. After they were sacrificed, the rat brains were examined by immunocytochemistry for Brdu and by immunofluorescence for NSE/Brdu.</p><p><b>RESULTS</b>The hippocampus NSCs of newborn rat could be well cultured and they expressed nestin and they could differentiate into NSE, GFAP. Most of NSCs survived in cerebral ventricle 4 weeks after transplantation in brain through Brdu immunocytochemistry and they migrated into regions of brain extensively, especially to the injured side of cortex and hippocampus. The number of living NSCs in the injured side of cortex and hippocampus of BDNF + NSCs transplantation group increased evidently and the percentage of NSCs differentiated into NSE was higher than that in the NSCs transplantation group (P < 0.05). The nerve function recovery of the rats in BDNF and NSCs treated group was significantly better than that in the other groups (P < 0.05). The NSCs group had no prominent changes as compared with the model groups (P > 0.05).</p><p><b>CONCLUSIONS</b>NSCs can be isolated from newborn rats hippocampus and cultured in vivo. NSCs can survive, migrate and differentiate into neurons through cerebral ventricle. BDNF could significantly accelerate proliferation and differentiation of NSCs transplanted into the brain of rats with HIBD. The nervous function recovery was improved prominently by transplantation of NSCs with BDNF application, which may become a potentially effective method to treat HIBD.</p>

Risk factors of post-renal biopsy bleeding / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the risk factors of post-renal biopsy bleeding (PBB).</p><p><b>METHODS</b>We retrospectively analyzed the clinical data of 1 262 patients who received ultrasound-guided biopsy of native kidney at our hospital from January 2005 to December 2006.</p><p><b>RESULTS</b>The overall incidence of PBB was 30.3% (383/1,262), among which the incidence of hematoma was 29.4% (371/1,262) (the percentages of less and more than 5cm were 73.9% and 26.1%, respectively) while that of gross hematuria was only 1.3% (17/1,262). The incidences of minor, intermediate, and major bleeding complications were 21.4% (270/1,262), 8.4% (106/1,262), and 0.6% (7/1,262), respectively. In seven patients with major bleeding complications, six had renal disease secondary to rheumatic disease (lupus nephritis, n = 5; scleroderma crisis, n = 1), while the other one had IgA nephropathy (Lee's classification V). The risk of PBB was relatively higher in women and younger patients.</p><p><b>CONCLUSIONS</b>Patients with chronic connective tissue diseases are vulnerable to severe PBB complications. A close monitoring of these patients is necessary.</p>

Expression of cyclooxygenase-2 in a mouse macula densa cell lines and signal transduction of NF-kappaB and AP-1 / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the effect of low salt (LS) on the expression of cyclooxygenase-2 (COX-2) and the activity of nuclear factor kappa B (NF-kappaB) and activator protein-1 (AP-1) in the mouse macula densa derived (MMDD1) cell line.</p><p><b>METHODS</b>MMDD1 cells were transfected with luciferase reporter plasmid containing AP-1 or NF-kappaB. Luciferase reporter assay was used to evaluate the effect of normal salt (NS) and low salt (LS) on the activities of NF-kappaB and AP-1. The changes of COX-2 expression were examined by RT-PCR. The expression of p-p38 MAPK, p-p44/42, c-Jun, c-Fos, and COX-2 in MMDD1 cells were analyzed by Western blot.</p><p><b>RESULTS</b>The expressions of COX-2 mRNA and protein in MMDD1 cells were significantly increased by LS (P < 0.01). Phosphorylated p38 and p44/42 MAP kinase were significantly increased by treatment at 180 min (P < 0.01). The up-regulated COX-2 protein expression with LS were significantly reduced with SB 203580 (p38 inhibitors) and PD-98059 (p44/42 inhibitors) (P < 0.01). The expressions of c-Jun and c-Fos were increased by LS. The luciferase activities of AP-1 and NF-kappaB were stimulated in LS (P < 0.01), the up-regulated luciferase activities were attenuated by PDTC at 25 micromol/L (NF-kappaB inhibitor) and curcumin at 20 micromol/L (AP-1 inhibitor) (P < 0.01). LS altered COX-2 mRNA abundance and protein expression were decreased in treatment with PDTC at 25 micromol/L, curcumin at 20 micromol/L (P < 0.01).</p><p><b>CONCLUSION</b>LS can induce the expression of COX-2 in MMDD1 cells, which may be involved in the activation of p38 MAP kinase, p44/42 kinase, AP-1, and NF-kappaB pathways.</p>

Clinical analysis of proteinuria and glomerular lesions in Henoch-Schönlein purpura nephritis of adults / 中国医学科学院学报

<p><b>OBJECTIVE</b>To analyze the characteristics of proteinuria and glomerular lesions in Henoch-Schönlein purpura nephritis (HSPN) of adults.</p><p><b>METHODS</b>The pathologic results and clinical data of 103 HSPN patients were analyzed.</p><p><b>RESULTS</b>Patients with mild or moderate proteinuria accounted for 40.8% and 37.9%, respectively. Patients with nephropathic proteinuria accounted for about 21.4%. Severer proteinuria resulted in higher blood pressure and increased cholesterol, and albumin decreased gradually (P < 0.01); meanwhile, total glomerular lesion, tubulointerstitial lesion, and vascular lesion also became severer (P < 0.01).</p><p><b>CONCLUSION</b>Proteinuria may indirectly reflect the severity of glomerular lesions in HSPN of adults.</p>

Clinical observation on treatment of postpartum hemorrhage by xuesaitong soft capsule / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Xuesaitong (XST) soft capsule in treating postpartum hemorrhage.</p><p><b>METHODS</b>Sixty pregnant women were randomly divided into the treated group (A) and the control group (B), 30 cases in each, they were treated with XST and placebo respectively for 7 days to observe the changes of hemorrhagic conditions.</p><p><b>RESULTS</b>After delivery, the hemoglobin, RBC count, hematocrit and cardiac index were lower at 3rd day than those before delivery in both groups (P < 0.05 or P < 0.01), reticulocyte count lowered insignificantly as compared with that before delivery in group A but significantly in control group B; the bleeding time shortened significantly in group A (P < 0.05) but unchanged in group B; significant change of blood viscosity only found in group B (P < 0.05). The amount of bleeding 30 min, 1 hr, 2 hrs and 24 hrs after delivery in group A was all lower than that in group B respectively (P < 0.01 or P < 0.05). Involution of uterus in group A at 2nd, 4th and 7th day after delivery was all better than that in group B respectively (P < 0.05).</p><p><b>CONCLUSION</b>XST has definite effect in decreasing postpartum hemorrhage, it also shows effects in promoting involution of uterus, reducing lochia and accelerating recovery of parturients.</p>