Research on mechanism of sildenafil protecting renal fibrosis in mice through AKT/GSK-3β signaling pathway / 医学研究生学报

ObjectiveRenal fibrosis is the basic pathological process of chronic kidney disease. To explore the protective effect of sildenafil (Sil) on renal fibrosis in mice, and provide experimental evidence for the clinical application of sildenafil in the treatment of renal fibrosis.Methods90 Kunming mice were randomly divided into three groups. Sham operation group (n=30), the mice only had ureteral separation, no ligation and ureteral clipping, which was subcutaneously injected with 0.9% NaCl solution in dose of 1 mL/(10 g·d); UUO model group (n=30), the UUO model was prepared by separating and ligating ureters in mice, and those were given subcutaneous injection with 0.9% NaCl solution in 1 mL/(10 g·d); UUO+Sil medicated group (n=30), mice were subcutaneously injected with sildena in 12 mg/(kg·d) at the same time every day for 14 days from the 1st day of UUO model. On the 3rd, 7th and 14th day, 10 mice whoes blood from eyeball was collected to determine serum creatinine and urea nitrogen were randomly selected from each group. HE and Masson staining were performed on the left kidney tissue to observe the pathological changes of the kidney tissue. The levels of Akt and GSK-3β protein and its phosphorylation in renal tissue were determined by western blot.ResultsAfter 3 days in UUO model, the contents of serum creatinine (63.10±2.90mol/L ) and urea nitrogen (12.87±0.40mmol/L) in the UUO group were significantly higher than those in the sham group [(26.00±3.70) mol/L, (8.07±0.60) mmol/L] (P<0.05). The contents of serum creatinine and urea nitrogen [(64.39±2.50) mol/L, (13.59±0.30) mmol/L] on the 7th day were higher than those in the sham group [(29.18±3.50) mol/L, (9.14±0.50) mmol/L] (P<0.05). The contents of serum creatinine and urea nitrogen [(64.39±2.50) mol/L, (15.03±0.50) mmol/L] on the 14th day were also significantly higher than those in the sham group [(29.74±2.50) mol/L, (9.90±0.20) mmol/L] (P<0.05). Compared with UUO group, the creatinine of mice on the 3rd, 7th and 14th day in the medicated group was lower (P<0.05). Compared with UUO group , urea nitrogen on the 3rd, 7th and 14th day in the medicated group was decreased (P<0.05). Compared with the sham operation group, the expression levels of p-AKT /Akt and p-GSK-3β/GSK-3β in the UUO group were significantly decreased (P<0.05), while the protein expression levels of p-AKT /Akt and p-GSK-3β/GSK-3β in the medicated group were significantly increased compared with the UUO group (P<0.05). On the 7th day in UUO model, there were many changes included atrophic renal tubular epithelial cells, dilated lumen, widened interstitium and more infiltrated inflammatory cells. On the 14th day in UUO, the above changes were more obvious, interstitial fibroblast hyperplasia and interstitial fibrosis, and the above pathological changes were reduced in the medicated group compared with the UUO model group. The collagen fibers in the UUO model group increased gradually with time. On the 14th day in UUO, the collagen fibers in the interstitium increased significantly, the tubular epithelium was damaged, and the red staining cells became lighter. These findings were less severe in the medicated group than in the UUO model group.ConclusionSildenafil can alleviate renal damage caused by renal fibrosis. Sildenafil inhibited renal fibrosis in UUO model, and its mechanism may be related to up-regulation of Akt/GSK3β pathway.

Research on mechanism of sildenafil protecting renal fibrosis in mice through AKT/GSK-3β signaling pathway / 医学研究生学报

ObjectiveRenal fibrosis is the basic pathological process of chronic kidney disease. To explore the protective effect of sildenafil (Sil) on renal fibrosis in mice, and provide experimental evidence for the clinical application of sildenafil in the treatment of renal fibrosis.Methods90 Kunming mice were randomly divided into three groups. Sham operation group (n=30), the mice only had ureteral separation, no ligation and ureteral clipping, which was subcutaneously injected with 0.9% NaCl solution in dose of 1 mL/(10 g·d); UUO model group (n=30), the UUO model was prepared by separating and ligating ureters in mice, and those were given subcutaneous injection with 0.9% NaCl solution in 1 mL/(10 g·d); UUO+Sil medicated group (n=30), mice were subcutaneously injected with sildena in 12 mg/(kg·d) at the same time every day for 14 days from the 1st day of UUO model. On the 3rd, 7th and 14th day, 10 mice whoes blood from eyeball was collected to determine serum creatinine and urea nitrogen were randomly selected from each group. HE and Masson staining were performed on the left kidney tissue to observe the pathological changes of the kidney tissue. The levels of Akt and GSK-3β protein and its phosphorylation in renal tissue were determined by western blot.ResultsAfter 3 days in UUO model, the contents of serum creatinine (63.10±2.90mol/L ) and urea nitrogen (12.87±0.40mmol/L) in the UUO group were significantly higher than those in the sham group [(26.00±3.70) mol/L, (8.07±0.60) mmol/L] (P<0.05). The contents of serum creatinine and urea nitrogen [(64.39±2.50) mol/L, (13.59±0.30) mmol/L] on the 7th day were higher than those in the sham group [(29.18±3.50) mol/L, (9.14±0.50) mmol/L] (P<0.05). The contents of serum creatinine and urea nitrogen [(64.39±2.50) mol/L, (15.03±0.50) mmol/L] on the 14th day were also significantly higher than those in the sham group [(29.74±2.50) mol/L, (9.90±0.20) mmol/L] (P<0.05). Compared with UUO group, the creatinine of mice on the 3rd, 7th and 14th day in the medicated group was lower (P<0.05). Compared with UUO group , urea nitrogen on the 3rd, 7th and 14th day in the medicated group was decreased (P<0.05). Compared with the sham operation group, the expression levels of p-AKT /Akt and p-GSK-3β/GSK-3β in the UUO group were significantly decreased (P<0.05), while the protein expression levels of p-AKT /Akt and p-GSK-3β/GSK-3β in the medicated group were significantly increased compared with the UUO group (P<0.05). On the 7th day in UUO model, there were many changes included atrophic renal tubular epithelial cells, dilated lumen, widened interstitium and more infiltrated inflammatory cells. On the 14th day in UUO, the above changes were more obvious, interstitial fibroblast hyperplasia and interstitial fibrosis, and the above pathological changes were reduced in the medicated group compared with the UUO model group. The collagen fibers in the UUO model group increased gradually with time. On the 14th day in UUO, the collagen fibers in the interstitium increased significantly, the tubular epithelium was damaged, and the red staining cells became lighter. These findings were less severe in the medicated group than in the UUO model group.ConclusionSildenafil can alleviate renal damage caused by renal fibrosis. Sildenafil inhibited renal fibrosis in UUO model, and its mechanism may be related to up-regulation of Akt/GSK3β pathway.

Analysis of prognostic factors of non-small cell lung cancer in patients under 40 years of age / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the prognostic factors for non-small cell lung cancer(NSCLC)in patients under 40 years of age.</p><p><b>METHODS</b>The clinicopathological data of 148 young patients with NSCLC were retrospectively analyzed. Kaplan-Meier and Cox regression analyses were used to analyze the relationship between prognostic factors and survival time.</p><p><b>RESULTS</b>The patients were followed-up for 6 - 148 months, and the follow-up rate was 100%. In the whole group, 122 patients died and 26 cases were surviving. The 1-, 3- and 5-year survival rates were 54.7%, 10.4% and 5.6%, respectively. The median survival time (MST) was 14.7 months. Kaplan-Meier analysis showed that Karnofsky performance status (KPS), clinical stage, treatment modality and serum CEA were related with prognosis (P < 0.05). Multivariate analysis indicated that KPS, clinical stage, treatment modality and serum CEA were independent prognostic factors (P < 0.05).</p><p><b>CONCLUSIONS</b>KPS, CEA, clinical stage and treatment modalities are independent prognostic factors in young NSCLC patients.</p>

Purification and properties of isoflavone-glucosidase / 生物工程学报

A high activity isoflavone-glucosidase, which hydrolysis glycosides, was obtainde using liquid fermentation from Absidia sp. R strain. The isoflavone-glucosidase was purified 11 folds with yielding rate of 10.9% after ammonium sulfate precipitation and DEAE-Cellocuse (DE-52) ion exchange chromatography. SDS-PAGE results showed that the molecular weight is 53kD. And the optimum temperature, the optimum pH, Km and pI of the enzyme are 50 deegrees C, 5.0, 1.3 x 10(-2) mol/L and 3.2, respectively. The isoflavone-glucosidase is also rather stable under 60 degrees C and in pH range from 5.0 to 7.0. The enzyme can be activated by Co2+ and Ca2+, and be inhibited by Ag+ and Cu2+.

Protective Effects of Prostaglandin E_1 on Newborn Rats with Hypoxic-ischemic Brain Damage / 实用儿科临床杂志

Objective To study the effect of exogenous prostaglandin E 1 (PGE 1) on the superoxide dismutase(SOD) and nitric oxide(NO) levels in brain tissue of neonatal rats with hypoxic-ischemic brain damage(HIBD).Methods Sixty 7-day old newborn Wistar rats to establish HIBD models,intraperitoneally and subcutaneous injected PGE 1 and TMP,then the rats were killed after hypo- xia and ischemia for 48 hours.Take cerebral cortex of arteria carotis ligation side and made them into homogenate to detect SOD and NO levels in brain tissue.Results SOD level in HIBD group was lower,and NO level was higher than those of normal group(P

Fermentative technology of Soybean Isofiavone Glucoside Hydrolase-Producing Strain / 微生物学通报

A high active soybean isoflavone glucoside hydrolase-producing mould strain was isolated from spirit qu. Its optimal hydrolase-producing conditions were as follows: 2.5% wheat bran as carbon source, 1% NaNO3 as nitrogen source, initial pH7. 0, culture medium volume 40mL/250mL, inoculating quantity 8% , culture temperature 30℃, revolutions 160r/min and culture time 84h. The enzyme activity reached 82 U/mL. Cu2+ can inhibit Absidia sp. R strain from producing the hydrolase, the influence of other metal ions was not remarkable on it.

Effects of Azithromycin on Hyperoxia Induced Lung Injury in Neonatal Rats / 实用儿科临床杂志

Objective To investigate the effects of azithromycin on hyperoxia induced lung injury in neonatal rats.Methods Ninety 2-day-old neonatal rats were randomly divided into 3 groups (30 cases in each group):air control group,hyperoxia model group,azithromycin treated group.The rats in air control group were exposed to indoor air,and the rats in hyperoxia model group and azithromycin group were exposed to 900 mL?L-1 O2 for 14 days.From 2-days-after birth,rats in treated group received intraperitoneal injection of azithromycin (200 mg?kg-1)per day,rats in air control group and hyperoxia model group received intraperitoneal injection of normal saline.Ten rats in each group were executed and their lung tissues were taken out and were observed under a optical microscope on the 3rd,7th,14th days from the start.The expression of interferon gamma(IFN-?),connective tissue growth factor(CTGF) and matrix metalloproteinase-9 (MMP-9) in the lung tissues were detected by immunohistochemistry.Results There was no expression of IFN-? positive cells in air control group,but the expressional intensity level was gradually enhanced as the time of inhaling hyperoxia prolonged in hyperoxia model group,it reached the peak on the 7th day,and then obviously declined on the 14th day,but still higher than that of air control group.The expressional intensity level of IFN-? in azithromycin treated group was lower than that of hyperoxia model group in each time segment,there were significant differences among them(Pa

Study on Epidemiology of Kawasaki Disease in Jilin Province from 1999 to 2008 / 实用儿科临床杂志

Objective To investigate the epidemiological characteristics and clinical prognosis of Kawasaki disease(KD) in Jilin pro-vince for recent 10 years.Methods The survey forms unified of standard KD epidemiology were used and sent to the province′s 32 hospitals above the county and city level with pediatric in-patients,in order to conduct a survey on the KD children during 10 years period from Jan.1,1999 to Dec.31,2008.SPSS 15.0 software was used to analyze the data.Results There were 93.75% of the survey forms came back.Five hundred and seventy-seven KD cases were reported from the 32 hospitals of 8 districts.The incidence of KD was of an increasing trend.It was 18 cases in 1999,while it was up to 122 cases in 2008.Male patients were 382 cases(66.2%),female patients were 195 cases(33.8%).The ratio of male and female was 1.96 to 1.The age of patients varied from 58 days to 14 years,those under 5 years of age accounted of 88.73%.Fourteen(2.4%) cases were found to have the sequelae of coronary artery disease.The ratio of male and female was 3.671.The younger the age,the higher the incidence of cardiac sequelae.The mainest cardiac sequelae was coronary artery ectasia.The time of visiting was(7.58?4.63) days after the onset.The KD children from 4 minority peoples including 50 cases accounted for 8.7%.The disease occurred all over the year,and had obvious season peak.Coronary artery lesions accounted for 63.26%.There was no death during acute pe-riod.The recurrence rate was 0.5%.Conclusions The incidence of KD in Jilin is in an increasing trend.The age and gender distribution are not exactly the same to pre-vious reports.There are two seasonal peaks including summer and winter,which is different to previous reports of domestic,United State,Japan.