Mechanism of Qizhenziyin mixture in the treatment of hypogonadism based on network pharmacology analysis and molecular docking / 药学实践杂志

Objective To investigate the mechanism of Qizhenziyin mixture in the treatment of hypogonadism by using the network pharmacology approach. Methods The active components of Qizhenziyin mixture were obtained by searching TCMSP ，TCMID and HIT databases.The related targets of candidate compounds were obtained by searching STITCH databases. The potential targets of Qizhenziyin mixture in the treatment of hypogonadism were obtained by mapping the disease genes of hypogonadism with Genecards and DisGeNet databases. The protein interaction platform database (STRING) was used to construct the interaction relationship between action targets. The target protein interaction （PPI） network was constructed by introducing Cytoscape software. The mechanism of Qizhenziyin mixture in the treatment of hypogonadism was explained through the enrichment analysis of GO, KEGG and molecular docking technology. Results A total of 148 drug-disease chemical compounds, 96 drug-disease intersection targets, 1085 disease targets were obtained；the components for treating diseases are: quercetin，kaempferol, luteolin, etc; enrichment analysis of GO revealed 1792 biological processes （BP）, 31 cellular components (CC) and 79 molecular functions (MF)；the results of KEGG pathway enrichment analysis indicated such as FOXO signaling pathway, prostate cancer, AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, etc.The results of molecular docking showed that kaempferol and LEP had the best and stable binding energy. Conclusion The active components of Qizhenziyin mixture may play a role of the treatment of hypogonadism by improving insulin resistance and the expression of testosterone synthetase of Leydig cells.

Anti-pseudo-allergic components in licorice extract inhibit mast cell degranulation and calcium influx / 中国天然药物

Pseudo-allergic reactions (PARs) widely occur upon application of drugs or functional foods. Anti-pseudo-allergic ingredients from natural products have attracted much attention. This study aimed to investigate anti-pseudo-allergic compounds in licorice. The anti-pseudo-allergic effect of licorice extract was evaluated in rat basophilic leukemia 2H3 (RBL-2H3) cells. Anti-pseudo-allergic compounds were screened by using RBL-2H3 cell extraction and the effects of target components were verified further in RBL-2H3 cells, mouse peritoneal mast cells (MPMCs) and mice. Molecular docking and human MRGPRX2-expressing HEK293T cells (MRGPRX2-HEK293T cells) extraction were performed to determine the potential ligands of MAS-related G protein-coupled receptor-X2 (MRGPRX2), a pivotal target for PARs. Glycyrrhizic acid (GA) and licorice chalcone A (LA) were screened and shown to inhibit Compound48/80-induced degranulation and calcium influx in RBL-2H3 cells. GA and LA also inhibited degranulation in MPMCs and increase of histamine and TNF-α in mice. LA could bind to MRGPRX2, as determined by molecular docking and MRGPRX2-HEK293T cell extraction. Our study provides a strong rationale for using GA and LA as novel treatment options for PARs. LA is a potential ligand of MRGPRX2.

Survey of Rehabilitation Nursing Management of Neurogenic Bladder and Clinical Application of Intermittent Catheterization in Guangdong, China / 中国康复理论与实践

Objective:To investigate the knowledgement and clinical application of neurogenic bladder and intermittent catheterization among nurses in Guangdong. Methods:From December, 2020 to January, 2021, 241 nurses in Guangdong were investigated with a questionnaire designed by ourselves. Results:The score was low in understanding the neurogenic bladder rehabilitation nursing management and intermittent catheterization through self-assessment. The awareness was deficient in the complication and risk management of neurogenic bladder. Although there were a lot of patients with dysuria in clinical practice, 67.2% of nurses still used indwelling catheter, and only 24.1% used intermittent catheterization. Only 9.9% nurses thought that patients with dysuria were treated positively by doctors. Most of nurses would like to participate in the training and nursing alliance in neurogenic bladder rehabilitation nursing management and intermittent catheterization, and manage patients with neurogenic bladder after discharge. Conclusion:The knowledge of guidelines related with neurogenic bladder and intermittent catheterization among nurses is insufficient, and is not applied in clinical practice. More work should be done to improve the knowledge and standardization of management of neurogenic bladder.

Value of high resolution magnetic resonance imaging for preoperative evaluation of Denonvilliers fascia in patients with rectal cancer / 中华胃肠外科杂志

Objective: Total mesorectal excision (TME) is the gold standard for surgical treatment of mid-low rectal cancer, but the postoperative incidence of urination and sexual dysfunction is relatively high. Preserving the Denonvilliers fascia (DF) during TME can reduce the postoperative incidence of urination and sexual dysfunction. In this study, high resolution magnetic resonance imaging (MRI) was used to observe the imaging performance and display of DF, so as to determine the value of this technique in preoperative evaluation of the preservation of DF. Methods: A descriptive cohort study was carried out. Clinical data of patients with rectal cancer who underwent TME and received preoperative high-resolution MRI at department of Gastrointestinal Surgery, the Third Affiliated Hospital of Sun Yat-sen University from August 2015 to June 2017 were retrospectively analyzed. The characteristics of DF were examined, and the shortest distance (d) between the anterior edge of tumor and DF was measured on high-resolution MRI. The distance d was compared between patients with stage T1-T2 and those with stage T3. Receiver operating characteristic (ROC) analysis was used to determine the predictive value of d for stage T1-T2 disease. Results: Thirty-two patients were enrolled in the study, including 27 males and 5 females with mean age of (62.9±8.9) years. DF was visualized in 96.9% (31/32) of cases on the T2WI sequence. The mean distance d in patients with stage T1-T2 disease (n=23) was (6.73±2.65) mm, and in those with stage T3 disease (n=9) was (1.30±1.15) mm (t=5.893, P<0.001). A cutoff of d >3 mm yielded specificity and positive predictive value for diagnosing stage T1-T2 disease of both 100%, sensitivity of 95.7% and negative predictive value of 90%. The optimum threshold of d was >3.05 mm, and Youden index was 0.957. Conclusions: High-resolution MRI can show the DF and accurately evaluate the relationship of DF with tumor in rectal cancer patients. Analysis on d value can provide an objective basis for the safe preservation of DF.

Effects of short-chain acyl-CoA dehydrogenase on hypertensive vascular remodeling / 中国病理生理杂志

AIM:To investigate the changes of short-chain acyl-CoA dehydrogenase(SCAD)in hypertensive vascular remodeling and to explore the relationship between SCAD and vascular remodeling in hypertension.METHODS:The spontaneously hypertensive rats(SHR;24 weeks old)and Wistar rats(24 weeks old)were used as experimental con-trol groups.The SHR and Wistar rats of 16 weeks old were trained by swimming as experimental groups.The systolic pres-sure was measured periodically.The thickness of vascular wall and the diameter of the vascular lumen were measured.The contents of ROS and ATP,the enzyme activity of SCAD, and the expression of SCAD at mRNA and protein levels in the aorta were determined.The free fatty acid in the serum and aorta was also measured.RESULTS:Compared with Wistar group,the diameter of vascular lumen decreased in SHR group.The thickness of vascular wall,the ratio of vascular wall and the diameter of vascular lumen,and the blood pressure in SHR group were increased significantly(P<0.05).Com-pared with SHR group,the diameter of vascular lumen increased in SHR +swim group.The thickness of vascular wall,the ratio of vascular wall and the diameter of vascular lumen,and the blood pressure in SHR +swim group were decreased sig-nificantly.Compared with control group, the expression of SCAD at mRNA and protein levels, the enzyme activity of SCAD,and the content of ATP were decreased in SHR group.However,the free fatty acid in the serum and aorta,and the content of ROS in the aorta were increased in SHR group.The expression of SCAD at mRNA and protein levels,the en-zyme activity of SCAD,the content of ATP were increased in Wistar +swim group and SHR +swim group.However, the free fatty acid in serum and aorta,and the content of ROS in the aorta were decreased in Wistar +swim group and SHR+swim group.CONCLUSION: Decrease in SCAD expression may be associated with hypertensive vascular remodeling. Swimming training can reverse hypertensive vascular remodeling by increasing the expression of SCAD in the aorta.

A study on Accompany Care Work Effects on Mental Anxiety and Depression of Empty-nest Elderly after Hip Replacement / 昆明医科大学学报

Objective To learn the effects on improving mental anxiety and depression in empty-nest elderly with hip replacement by accompany care work, and the factors influencing psychological anxiety and depression after hip replacement in empty-nest eldly. Then to explore comprehensive nursing strategies for hip arthroplasty in empty-nest eldly. Methods We investigated empty-nest elderly with hip arthroplasty by using homemade questionnaire, SAS and SDS scale between november 2015 and october 2017. Different nursing methods were used to treat empty-nesters in different groups, and the influencing factors of anxiety and depression were analyzed.Results It is not statistically significant in demographic characteristics (χ2＜3.84, P＞0.05) and anxiety (t = 1.2037, P=0.2308) and depression (t =1.0094, P=0.3142) at the time of entering the hospital, etc. Patients anxiety is statistically significant at time of discharge (t =-5.0159, P≤0.001) and one month after discharge (t =-9.5160, P ＜ 0.001), Patients depression is statistically significant at time of discharge (t =-2.9271, P = 0.0039) and one month after discharge (t =-8.2383, P＜0.001).The factors causing anxiety is nursing mode, number of chronic diseases and postoperative complications. The factors causing depression are economic income, nursing mode, and number of chronic diseases.Conclusion Accompany care work can improve the problems of anxiety and depression in an empty-nest eldly man after hip replacement. It is related to anxiety in nursing patterns, chronic diseases, postoperative complications.Meanhiwle while depression is related to economic income, nursing patterns, and types of chronic diseases, etc.

Characteristics, Management, and Outcomes of Acute Heart Failure in the Emergency Department: A Multicenter Registry Study with 1-year Follow-up in a Chinese Cohort in Beijing / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The emergency department (ED) has a pivotal influence on the management of acute heart failure (AHF), but data concerning current ED management are scarce. This Beijing AHF Registry Study investigated the characteristics, ED management, and short- and long-term clinical outcomes of AHF.</p><p><b>METHODS</b>This prospective, multicenter, observational study consecutively enrolled 3335 AHF patients who visited 14 EDs in Beijing from January 1, 2011, to September 23, 2012. Baseline data on characteristics and management were collected in the EDs. Follow-up data on death and readmissions were collected until November 31, 2013, with a response rate of 92.80%. The data were reported as median (interquartile range) for the continuous variables, or as number (percentage) for the categorical variables.</p><p><b>RESULTS</b>The median age of the enrolled patients was 71 (58-79) years, and 46.84% were women. In patients with AHF, coronary heart disease (43.27%) was the most common etiology, and myocardium ischemia (30.22%) was the main precipitant. Most of the patients in the ED received intravenous treatments, including diuretics (79.28%) and vasodilators (74.90%). Fewer patients in the ED received neurohormonal antagonists, and 25.94%, 31.12%, and 33.73% of patients received angiotensin converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, and spironolactone, respectively. The proportions of patients who were admitted, discharged, left against medical advice, and died were 55.53%, 33.58%, 7.08%, and 3.81%, respectively. All-cause mortalities at 30 days and 1 year were 15.30% and 32.27%, respectively.</p><p><b>CONCLUSIONS</b>Substantial details on characteristics and ED management of AHF were investigated. The clinical outcomes of AHF patients were dismal. Thus, further investigations of ED-based therapeutic approaches for AHF are needed.</p>

Short-term rosuvastatin treatment for the prevention of contrast-induced acute kidney injury in patients receiving moderate or high volumes of contrast media: a sub-analysis of the TRACK-D study / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Current randomized trials have demonstrated the effects of short-term rosuvastatin therapy in preventing contrast-induced acute kidney injury (CIAKI). However, the consistency of these effects on patients administered different volumes of contrast media is unknown.</p><p><b>METHODS</b>In the TRACK-D trial, 2998 patients with type 2 diabetes and concomitant chronic kidney disease (CKD) who underwent coronary/peripheral arterial angiography with or without percutaneous intervention were randomized to short-term (2 days before and 3 days after procedure) rosuvastatin therapy or standard-of-care. This prespecified analysis compared the effects of rosuvastatin versus standard therapy in patients exposed to (moderate contrast volume [MCV], 200-300 ml, n = 712) or (high contrast volume [HCV], ≥ 300 ml, n = 220). The primary outcome was the incidence of CIAKI. The secondary outcome was a composite of death, dialysis/hemofiltration or worsened heart failure at 30 days.</p><p><b>RESULTS</b>Rosuvastatin treatment was associated with a significant reduction in CIAKI compared with the controls (2.1% vs. 4.4%, P = 0.050) in the overall cohort and in patients with MCV (1.7% vs. 4.5%, P = 0.029), whereas no benefit was observed in patients with HCV (3.4% vs. 3.9%, P = 0.834). The incidence of secondary outcomes was significantly lower in the rosuvastatin group compared with control group (2.7% vs. 5.3%, P = 0.049) in the overall cohort, but it was similar between the patients with MCV (2.0% vs. 4.2%, P = 0.081) or HCV (5.1% vs. 8.8%, P = 0.273).</p><p><b>CONCLUSIONS</b>Periprocedural short-term rosuvastatin treatment is effective in reducing CIAKI and adverse clinical events for patients with diabetes and CKD after their exposure to a moderate volume of contrast medium.</p>

Takotsubo cardiomyopathy in a 90-year-old Chinese man / 中华医学杂志(英文版)

A 90-year-old Chinese man was transferred to the Emergency Department of the Affiliated Shantou Hospital of Sun Yat-sen University for treatment of an acute myocardial infarction. He suffered chest pain with three days of cough, dyspnea and fever. A diagnosis of Takotsubo cardiomyopathy was made in normal coronary arteries from urgent coronary angiography and characteristic apical dyskinesis and basal hyper contractility in left ventriculography. The patient died from severe multi-organ failure on the second day of hospitalization.

Clinical value of plasma N-terminal pro-brain natriuretic peptide in diagnosis of diastolic heart dysfunction / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the clinical value of plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) detection in the diagnosis of diastolic heart dysfunction.</p><p><b>METHODS</b>Ninety patients with diastolic heart dysfunction and left ventricular ejection fraction (LVEF)>or=45% were divided into 3 groups according to the findings by conventional echocardiography and/or tissue Doppler imaging, namely impaired relaxation pattern group (n=58), pseudonormal pattern group (n=22) and restrictive filling pattern group (n=10). Ten patients with normal heart function served as the control group. Plasma NT-proBNP level was determined in all the subjects and its correlation to diastolic heart dysfunction was analyzed.</p><p><b>RESULTS</b>Compared with the control group, all the 3 case groups had significantly higher plasma NT-proBNP level (P<0.01). Plasma NT-proBNP level increased gradually with the severity of diastolic dysfunction. Spearman rank correlation analysis indicated that lg(NT-proBNP) was positively correlated to the severity of diastolic dysfunction. Simple linear regression showed that 52.7% of the total variation of lg(NT-proBNP) was correlated to the severity of the condition. The ROC curve demonstrated a sensitivity of 80%, specificity of 90%, positive predictive value of 84.2% and the negative predictive value of 87.1% for NT-proBNP level of 133 ng/L in predicting diastolic heart dysfunction regardless of the clinical manifestations, and the sensitivity was 81.7% and specificity was 75% for NT-proBNP level at 280.25 ng/L in predicting symptomatic diastolic heart dysfunction; the sensitivity was 81.2% and the specificity was 92.6% for NT-proBNP at 655 ng/L in predicting moderate to severe diastolic heart dysfunction.</p><p><b>CONCLUSION</b>Plasma NT-proBNP level increases gradually with the severity of diastolic dysfunction and has a high clinical value in severity rating and assisting the diagnosis of diastolic dysfunction.</p>

Apelin protects against cardiomyocyte apoptosis induced by glucose deprivation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Apoptosis is a major cause of ischemic heart dysfunction. Apelin, the endogenous ligand for the G-protein-coupled APJ receptor, has been reported to exert cardioprotective effects during myocardial injury. The aim of this study was to investigate the effects of apelin on apoptosis of rat cardiomyocytes induced by glucose deprivation (GD) and study the related signaling pathway.</p><p><b>METHODS</b>Apelin and APJ mRNA expression were determined by RT-PCR in neonatal rat cardiomyocytes during different durations of GD. Cardiomyocyte apoptosis was detected by annexin V-FITC/propidium iodide (PI) staining after GD for 12 hours with or without apelin-13 (10 and 100 nmol/L) pretreatment. Protein levels of Akt and the mammalian target of rapamycin (mTOR) as well as cell apoptosis were detected in the presence or absence of LY294002 (a phosphatidylinositol 3-kinases (PI3K) inhibitor) or rapamycin (a mTOR inhibitor).</p><p><b>RESULTS</b>Apelin mRNA expression was up-regulated when cardiomyocytes were exposed to GD for 6, 12, 18, and 24 hours compared with the base level (P > 0.05, P < 0.01, P < 0.01, P < 0.01). However, when cardiomyocytes were exposed to GD for up to 36 hours, apelin mRNA expression was 17% lower than the base level (P < 0.05). APJ mRNA expression paralleled that of apelin. Apelin-13 pretreatment at 100 nmol/L significantly inhibited GD-induced cardiomyocyte apoptosis (P < 0.05) and increased Akt and mTOR phosphorylation (P < 0.01, P < 0.01). At the same time apelin-13 (100 nmol/L) up-regulated Bcl-2 protein expression and down-regulated Bax and cleaved caspase-3 expression (P < 0.01, P < 0.05, P < 0.05). The anti-apoptotic effect of apelin-13 was blocked by LY294002 (P < 0.01) but not by rapamycin.</p><p><b>CONCLUSIONS</b>The endogenous apelin-APJ system is compensatorily up-regulated and ultimately down-regulated following sustained myocardial ischemia. Apelin protects against ischemic cardiomyocyte apoptosis via activation of the PI3K/Akt pathway.</p>

Relationship between nuclear factor kappa B signal transduction way and the sensitivity of tongue carcinoma cell to Pingyangmycin chemotherapy / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To examine the relationship between NF-kappaB signal transduction way and the sensitivity of Tca8113 carcinoma cell to Pingyangmycin chemotherapy.</p><p><b>METHODS</b>2 mg/L antisense p65 oligodeoxynucle-otides (5'-GAACAGTTCGTCCATGGCCG-3') was transfected into Tca8113 cells through Lepofectin vectin, then the cells were treated with 8 mg/L Pingyangmycin. After 3 h and 6 h, the expression of p65 in nucleus was studied with immunohistochemical methods and Western blot analyses. After 48 h, the inhibitory rate of cell growth was detected with MTT assay.</p><p><b>RESULTS</b>The NF-kappaB/p65 signal transduction way in Tca8113 cells was activated after treated with Pingyangmycin. But the transfection of antisense p65 oligodeoxynucle-otides inhibited the activation of the signal transduction, the p65 expression in nucleus was decreased significantly (P < 0.05) at 6 h, and the inhibitory rate of cell growth was increased significantly (P < 0.05) at 48 h.</p><p><b>CONCLUSION</b>The results suggested the chemotherapeutic sensitivity of Tca8113 carcinoma cell to Pingyangmycin was improved by the inhibition of NF-kappaB/p65 signal transduction.</p>

Total thyroidectomy with a modified Miccoli's approach for treatment of Graves' disease--feasibility and its applying techniques / 浙江大学学报·医学版

<p><b>OBJECTIVE</b>To assess the feasibility and relevant applying techniques of total thyroidectomy for Graves' disease with a modified Miccoli's approach.</p><p><b>METHODS</b>Forty-two patients with Graves' disease consecutively received the radical operation from June 2002 to December 2004.The modification includes: (1) Incision extending according to the degree of lobe enlargement (3-6 cm, average 4 cm); (2) A space maintain-regulating device was used to change dimensionally the volume of working space (mainly height) when specific manipulation needed; (3) A volume-reducing resection step was performed for the gland with degree III hyperplasia by cutting off the middle-inferior part of the lobe prior to endoscopic lobectomy. The approach was designed to mainly use ultrasonically-activated scalpels, with suction-dissector or others as supplementary instruments. During the operations, a method of "sequenced dissect-coagulate-cut" was employed to directly divide all branches of thyroid vessels without ligation or application of hemoclips.</p><p><b>RESULTS</b>All procedures were completed successfully. None of them were converted to open surgery due to uncontrolled bleeding or severe postoperative hematoma. No severe complications occurred, except 2 cases who suffered from temporary hoarseness.</p><p><b>CONCLUSION</b>Total thyroidectomy for Graves' disease can be safely performed with the modified Miccoli's approach by using ultrasonic scalpel and the space maintain-regulating device. Application of these adaptive reforms can obviously reduce the difficulties in manipulation, and thus, make the usage of this minimally invasive design also clinically possible for even radical treatment of the gland.</p>

The experimental study on pathological changes of pulmonary tissues in portal hypertensive rabbits with schistosomal cirrhosis / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the pathologic features of the pulmonary tissue in portal hypertensive rabbits with schistosomal cirrhosis, and to study the role of endothelin-1 (ET-1) and nitric oxide (NO) in pathogenesis of portal hypertensive pulmonary vasculopathy.</p><p><b>METHODS</b>The experimental group included 10 rabbits infected percutaneously with cercariae of Schistosomiasis Japonica. The control group included 10 normal rabbits. HE stain, Masson trichrome stain and transmission electron microscopy were applied to detect the pathologic features of the pulmonary tissue. The expression and distribution of endothelin-1 (ET-1) and nitric oxide synthase (NOS) in the lung tissues were analyzed by immunohistochemistry.</p><p><b>RESULTS</b>After 120 d, the pathological morphology alteration of the pulmonary tissue was observed in the rabbits in experimental group. Both of ET-1 and NOS-containing cells were more abundant in distribution and expression in the lung tissue of experimental group than those of the control group. There was significant difference between the two groups in the parameter of area, lightness and gray level of ET-1 and NOS (P < 0.01).</p><p><b>CONCLUSIONS</b>Pulmonary pathologic changes occur in the portal hypertensive rabbits with schistosomal cirrhosis. ET-1 and NOS-containing cells are more abundant in pulmonary vessel of portal hypertension, then followed by dilation of intrapulmonary vessel. It is deduced that ET-1 and NO might play an important role in the pathogenesis of portal hypertensive pulmonary vasculopathy.</p>

High expression of p65 transcription factor and its significance in tongue carcinoma / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To examine the correlation between p65 expression and the metastasis and prognosis in tongue carcinoma.</p><p><b>METHODS</b>The immunohistochemical expression of p65 was examined in 50 cases of tongue carcinoma, and the clinical and histopathologic records were retrospectively analyzed.</p><p><b>RESULTS</b>Overexpression of p65 in cytoplasma and nucleus was found in 64% cases of tongue carcinoma. There was significant difference of p65 expression among different TNM stages, and the higher expression rate of p65 was found in higher stages. Overexpression of p65 was also related to lymph node metastasis. Significantly greater increase in expression levels of p65 was found in the metastatic cases (n = 22) compared to the nonmetastatic cases (n = 10). However, there was no significant difference of p65 expression among different histopathologic grading. The 5-year survival rate of p65 positive and negative group was 59.3% and 88.9% respectively, and there was significant difference in Kaplan-Meier survival curve (chi2 = 5.6, P < 0.05).</p><p><b>CONCLUSION</b>The results suggest that the expression of p65 was important to predict the metastasis and prognosis in tongue carcinoma.</p>

Cyclosporin A inhibits the adhesion of neutrophil with ECV-304 induced by hypoxia/reoxygenation via ROS-Cyclophilin A-ERK1/2 pathway / 生理学报

To investigate the inhibition of cyclosporin A (CsA) on neutrophil adhesion to human umbilical vein endothelial cells (HUVECs, ECV-304) induced by hypoxia/reoxygenation and further explore its mechanism, a 1 h hypoxia/4 h reoxygenation model was reproduced using ECV-304. The adhesion rate of neutrophils to ECV-304 was determined by measuring the activity of endogenous hexosaminidase. The expression of endothelial cell adhesion molecules of E-selectin and ICAM-1 was measured by flow cytometry. The expression of cyclophilin A (CyPA) and the activation of ERK1/2 was compared among experimental groups by Western blot. The content of reactive oxygen species (ROS) was measured by Fenton reaction. After being stimulated with 1 h hypoxia/4 h reoxygenation, ECV-304 showed an enhanced neutrophil adhensiveness in association with an increased surface expression of E-selectin and ICAM-1. In parallel, the content of ROS was also increased. These effects were significantly suppressed by the addition of CsA. Most importantly, the expression of CyPA was significantly increased following 1 h hypoxia/4 h reoxygenation, which was accompanied with an increased activation of ERK1/2. Treatment with CyPA inhibitor CsA and CyPA antisense oligonucleotides significantly inhibited the activation of ERK1/2 and decreased the adhesion of neutrophils to ECV-304. The specific ERK1/2 inhibitor PD98059 caused an inhibition of neutrophil adhesion to hypoxia/reoxygenation-stimulated ECV-304. Our data confirm that CsA inhibits neutrophil adhesion to hypoxia/reoxygenation stimulated ECV-304 by a mechanism involving inhibition of the signal transduction of ROS, CyPA and ERK1/2.

MUTATION BREEDING OF HIGH COLISTIN PRODUCTION STRAINS / 微生物学通报

A colistin producing strain Paenibacillus polymyxa AS1.541 was treated by N-methyl-N-nitro-N-nitrosoguanidine(NTG) for increasing yields of the antibiotic colistin.High-yield strains were obtained by selection of deregulated mutant which grow on media containing colistin,a self second metabolite,and ethionine,an analogue of methionine.Some of these mutants have higher yield of colistin than that of the parent strain.