Erythropoietin-derived peptide ARA290 mediates brain tissue protection through the ß-common receptor in mice with cerebral ischemic stroke.

AIM: To explore the neuroprotective effects of ARA290 and the role of ß-common receptor (ßCR) in a mouse model of middle cerebral artery occlusion (MCAO). METHODS: This study included male C57BL/6J mice that underwent MCAO and reperfusion. The neuroprotective effect of ARA290 on MCAO-induced brain injury was investigated using neurological function tests (Longa and modified neurological severity score). Cerebral infarction was examined by 2, 3, 5-triphenyl tetrazolium chloride staining, neuronal apoptosis was assessed by immunofluorescence staining, blood parameters were measured using a flow cytometry-based automated hematology analyzer, liquid chromatography with tandem mass spectrometry was used to identify the serum metabolomics signature, inflammatory cytokines and liver index were detected by commercially available kits, and the protein levels of the erythropoietin (EPO) receptor and ßCR were measured by western blot. RESULTS: ARA290 exerted a qualitatively similar neuroprotective effect after MCAO as EPO. ARA290 significantly reduced neuronal apoptosis and the level of inflammatory cytokines in the brain tissue. However, ARA290's neuroprotective effect was significantly suppressed following the injection of siRNA against ßCR. CONCLUSION: ARA290 provided a neuroprotective effect via ßCR in cerebral ischemic mice without causing erythropoiesis. This study provides novel insights into the role of ARA290 in ischemic stroke intervention.

[Two new prenylated 2-arylbenzofurans from roots of Artocarpus heterophyllus and their anti-respiratory burst activities].

Two prenylated 2-arylbenzofurans were isolated from roots of Artocarpus heterophyllus, with a combination of various chromatographic approaches, including ODS, MCI, Sephadex LH-20, and semipreparative high performance liquid chromatography(HPLC). They were identified as 5-[6-hydroxy-4-methoxy-5,7-bis(3-methylbut-2-enyl)benzofuran-2-yl]-1,3-benzenediol(1) and 5-[2H,9H-2,2,9,9-tetramethyl-furo[2,3-f]pyrano[2,3-h][1]benzopyran-6-yl]-1,3-benzenediol(2) with spectroscopic methods, such as HR-ESI-MS, IR, 1D NMR, and 2D NMR, and named artoheterins B(1) and C(2), respectively. The anti-respiratory burst activities of the two compounds were evaluated with rat polymorphonuclear neutrophils(PMNs) stimulated by phorbol 12-myristate 13-acetate(PMA). The results showed that 1 and 2 exhibited significant inhibitory effect on respiratory burst of PMNs with IC_(50) values of 0.27 and 1.53 µmol·L~(-1), respectively.

[Value of three-dimensional speckle-tracking imaging in evaluating left ventricular systolic function and its correlation with peripheral arterial elasticity in children with simple obesity: a prospective study]. / ä¸‰ç»´æ–‘ç‚¹è¿½è¸ªæˆåƒæŠ€æœ¯å¯¹å•çº¯æ€§è‚¥èƒ–å„¿ç«¥å·¦å¿ƒå®¤æ”¶ç¼©åŠŸèƒ½çš„è¯„ä»·åŠå ¶ä¸Žå¤–å‘¨åŠ¨è„‰å¼¹æ€§ç›¸å ³æ€§çš„å‰çž»æ€§ç ”ç©¶.

OBJECTIVES: To study the application of three-dimensional speckle-tracking imaging in evaluating left ventricular systolic function and its correlation with peripheral arterial elasticity in children with simple obesity. METHODS: Random sampling combined with convenience sampling was used to obtain research samples, and then the samples were divided into an obesity group (23 cases), an overweight group (21 cases), and a normal group (24 cases). Three-dimensional speckle-tracking imaging was used to measure the global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS) of the left ventricle. An automatic arteriosclerosis tester was used to measure ankle-brachial index (ABI) and brachial-ankle pulse wave velocity (baPWV). These parameters were compared among the three groups. The correlation of three-dimensional speckle-tracking parameters with ABI and baPWV was evaluated. RESULTS: There were no significant differences in GLS, GRS, and GCS between the obesity and normal groups (P>0.05). The overweight group had a significantly higher GLS than the normal group [(-24±7) vs (-19±12), P<0.05]. The obesity and overweight groups had a significantly lower ABI than the normal group [(1.00±0.09)/(1.09±0.13) vs (2.25±0.13), P<0.05). The obesity group had a significantly higher baPWV than the normal group [(978±109) vs (905±22), P<0.05]. In the children with obesity, GLS was positively correlated with baPWV (r=0.516, P<0.05) , but not correlated with ABI (P>0.05), and GCS and GRS had no significant correlation with ABI or baPWV (P>0.05). CONCLUSIONS: There are varying degrees of changes in left ventricular systolic function and peripheral arterial elasticity in children with simple obesity, and there is a certain correlation between them.

Erythropoietin promotes the differentiation of fetal neural stem cells into glial cells via the erythropoietin receptor-ß common receptor/Syne-1/H3K9me3 pathway.

AIMS: To investigate the effect of erythropoietin (EPO) on the differentiation of neural stem cells (NSCs)/neural progenitors (NPs) in the treatment of hypoxic-ischemic injury and its potential mechanisms. METHODS: Fetal NSCs/NPs were treated with EPO after oxygen and glucose deprivation/reoxygenation (OGD/R). Cell viability, proliferation, and differentiation of NSCs/NPs were detected by CellTiter-Glo, Edu assay, flow cytometry, and quantitative real-time PCR (qPCR). Immunofluorescence staining, co-immunoprecipitation (Co-IP), and western blotting were used to test the existence of EPO receptor/ß common receptor (EPOR/ßCR) heterodimer on NSCs/NPs and the possible pathway. RESULTS: EPO treatment at different time points increased cell viability without affecting proliferation. EPO treatment immediately after OGD/R promoted oligodendrocyte and astrocyte differentiation, while decreasing neuronal differentiation of NSCs/NPs. EPOR/ßCR heterodimer existed on the cell surface of the fetal cortical NSCs/NPs, EPO treatment significantly increased the mRNA expression of ßCR and elevated the correlation between EPOR and ßCR levels. In addition, mass spectrometry analysis identified Syne-1 as a downstream signaling molecule of the EPOR/ßCR heterodimer. Immunofluorescence staining and western blotting indicated that the ßCR/Syne-1/H3K9me3 pathway was possibly involved in the differentiation of fetal neural stem cells into the glial cell effect of EPO. CONCLUSION: EPO treatment immediately after OGD/R could not facilitate fetal NSCs/NPs neurogenesis but promoted the formation of the EPOR/ßCR heterodimer on fetal NSCs/NPs, which mediates its function in glial differentiation.

Predicting Metabolic Syndrome Using Anthropometric Indices among Chinese Adolescents with Different Nutritional Status: A Multicenter Cross-sectional Study.

OBJECTIVE: To evaluate the predictive performance of anthropometric indices for metabolic syndrome (MetS) among Chinese adolescents with different nutritional status. METHODS: We recruited 9,513 adolescents aged 10-18 years from seven provinces in China during September 2014. Anthropometric indices and blood pressure were measured at recruitment, and blood samples were collected for determining fasting plasma glucose and lipid profile. Receiver operating characteristic (ROC) analyses were used to assess the predictive performance of anthropometric indices, including body mass index (BMI) percentile, waist circumference percentile, waist-height ratio, and waist-hip ratio. RESULTS: Overall, the four anthropometric indices showed good accuracy for predicting MetS with areas under ROC curves (AUCs) ranging from 0.86 to 0.94; similar AUCs ranging from 0.73 to 0.99 were observed for participants with normal weight. The performance of all four indices was poor in overweight and obese participants, with AUCs ranging from 0.66 to 0.77 and from 0.60 to 0.67, respectively. Waist circumference showed relatively better performance in all the subgroup analyses. CONCLUSIONS: We suggest using anthropometric indices with the cutoff values presented here for predicting MetS in the overall and normal-weight adolescent population, but not in the overweight and obese adolescent population where more specific screening tests are required.

[Effect of toothpaste containing emulsifier 30 and sodium lauryl sulfate surfactant on the integrity of oral epithelium].

PURPOSE: To investigate the effect of toothpaste containing emulsifier 30 and sodium lauryl sulfate surfactant on the integrity of oral epithelium. METHODS: Sixty individuals equally divided into 2 groups by random number table methods. Group A received toothpaste containing emulsifier 30, while group B received fluoride toothpaste containing sodium lauryl sulfate (SLS) surfactant. The exfoliation of oral soft tissue was evaluated before, 30 minutes and 4 days after the test. The fluoride concentration in plaque and saliva was compared between the two groups. The data were processed with SPSS 22.0 software package. RESULTS: The scores of oral soft tissue exfoliation at 30 min and 4 d after the test were increased significantly (P<0.05). The scores of subgingival, supragingival, oral apex and oral soft tissue exfoliation of group A at 30 min after using the paste were significantly lower than those 4 days after using the paste(P<0.05), while no significant change was observed in the score of oral soft tissue exfoliation at the dorsal tongue(P>0.05). The total scores of subgingival, supragingival, dorsal tongue, ventral tongue and oral soft tissue exfoliation in group B 30 min after using the paste were significantly higher than those at 4 d after use, and the score of oral soft tissue exfoliation at oral apex was significantly lower than that at 4 d after use (P<0.05).The total scores of subgingival, supragingival, dorsal tongue, ventral tongue and oral soft tissue exfoliation in group B at 30 min after using the paste were significantly higher than those of group A, while the score of oral soft tissue exfoliation at oral apex was significantly lower than that of group A(P<0.05).The total scores of subgingival, supragingival, ventral tongue and oral soft tissue exfoliation in group B at 4 d after using the paste were significantly higher than those of group A(P<0.05). The scores of oral soft tissue exfoliation at oral apex and dorsal tongue at 4 d after use had no significant difference between the two groups (P>0.05). The fluoride concentration in plaque and saliva was increased significantly in both groups after test(P<0.05). CONCLUSIONS: Both fluoride toothpaste containing emulsifier 30 and SLS surfactant cause a certain degree of oral soft tissue exfoliation. In comparison, fluoride toothpaste containing emulsifier 30 has less oral soft tissue damage; moreover, the two fluoride toothpastes can effectively inhibit acid production of plaque bacteria and prevent occurrence of caries.

Long-term exposure to ambient air pollution and metabolic syndrome in children and adolescents: A national cross-sectional study in China.

BACKGROUND: The prevalence of metabolic syndrome (MetS) rapidly increased over the past decades. However, little evidence exists about the effects of long-term exposure to ambient air pollution on MetS in children and adolescents. OBJECTIVE: This study aims to assess the association between long-term ambient air pollution and the prevalence of MetS in a large population of Chinese children and adolescents. METHODS: In 2013, a total of 9,897 children and adolescents aged 10 to 18 years were recruited from seven provinces/municipalities in China. MetS was defined based on the recommendation by the International Diabetes Federation (IDF). Satellite based spatio-temporal models were used to estimate exposure to ambient air pollution (including particles with diameters ≤1.0 µm (PM1), ≤2.5 µm (PM2.5), and ≤10 µm (PM10), and nitrogen dioxide (NO2)). Individual exposure was calculated according to 94 schools addresses. After adjustment for a range of covariates, generalized linear mixed-effects models were utilized to evaluate the associations between air pollutants and the prevalence of MetS and its components. In addition, several stratified analyses were examined according to sex, weight status, outdoor physical activity time, and sugar-sweetened beverages (SSBs) intake. RESULTS: The prevalence of MetS was 2.8%. The odds ratio of MetS associated with a 10 µg/m3 increase in PM1, PM2.5, PM10 and NO2 was 1.20 (95%CI: 0.99, 1.46), 1.31 (95%CI: 1.05, 1.64), 1.32 (95%CI: 1.08, 1.62), and 1.33 (95%CI: 1.03, 1.72), respectively. Regarding the MetS components, we observed associations between all pollutants and abdominal obesity. In addition, long-term PM1 and NO2 exposures were associated with the prevalence of elevated fasting blood glucose. Stratified analyses detected that the associations between air pollutants and the prevalence of MetS were stronger in boys (Pinteraction < 0.05). CONCLUSIONS: We found that long-term exposure to PM2.5, PM10, and NO2 were positively associated with the prevalence of MetS in children and adolescents. Our findings may have certain public health implications for some comprehensive strategy of environment improvement and lifestyles changes in order to reduce the burden of non-communicable disease.

Greenness surrounding schools and adiposity in children and adolescents: Findings from a national population-based study in China.

BACKGROUND: Previous studies have indicated that exposure to green space may benefit human health. However, the available evidence concerning the effects of greenness, especially school-based greenness, on pediatric obesity is scarce. OBJECTIVE: To explore the association between school-based greenness and adiposity in children and adolescents in China. METHOD: We conducted a nationwide cross-sectional study of 56,620 children and adolescents (aged 6-18 years) in seven provinces/municipalities across China. School-based greenness was assessed using satellite-derived Normalized Difference Vegetation Index (NDVI) and Soil Adjusted Vegetation Index (SAVI) within 100-, 500-, and 1000-m circular buffers around each school's address. Generalized linear mixed regression models were used to estimate associations of greenness with BMI z-scores (zBMI), waist circumference, and prevalent overweight/obesity. We also explored the potential mediating role of ambient air pollution and physical activity in the greenness-adiposity associations. RESULT: In the adjusted model, an IQR increase in NDVI-1000m was associated with lower zBMI (ß: -0.11, 95% confidence interval[CI]: -0.13,-0.09) and waist circumference (ß: -0.64, 95%CI: -0.78,-0.50). Consistently, an IQR increase in NDVI-100m, NDVI-500m, NDVI-1000m was associated with 7-20% lower odds of overweight/obesity in the adjusted models. Air pollutants mediated 6.5-29.1% of the association between greenness and zBMI. No significant mediation effect was observed for physical activity. CONCLUSION: Higher school-based greenness levels were associated with lower zBMI, waist circumference, and lower odds of overweight and obesity in children and adolescents. Ambient air pollutants may partially mediate the greenness-adiposity associations.

The Chinese herb Fructus Broussonetiae aids learning and memory in chronic cerebral hypoperfusion by reducing proinflammatory microglia activation in rats.

The neuroprotective role of Fructus Broussonetiae in a model of chronic cerebral hypoperfusion with cognitive decline was focused on neural plasticity and microglia/macrophage polarization. Chronic cerebral hypoperfusion was induced by bilateral common carotid artery ligation. Fructus Broussonetiae shortened escape latency and added the number of platform crossings of rats, up-regulated the expression of synaptophysin in the gray matter and increased myelin basic protein expression in the white matter. Further mechanistic experiments were conducted to examine microglia activation and M1/M2 polarization. It was shown that Fructus Broussonetiae reduced the activation of microglia revealed by decreased expression of ionized calcium-binding adapter molecule-1, inhibited M1 polarization of microglia and improved microglial M2 polarization shown by down-regulated the expression of inducible nitric oxide synthase and Fc fragment of IgG receptor IIIa and up-regulated the expression of arginase-1. In conclusion, the Chinese herb Fructus Broussonetiae can improve cognitive function following chronic cerebral hypoperfusion by down-regulating the activation of microglia, inhibiting microglial M1 polarization, and improving neural plasticity.

Huoluo Yinao decoction mitigates cognitive impairments after chronic cerebral hypoperfusion in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Huoluo Yinao decoction (HLYND) has been used to ameliorate cognitive impairment induced by chronic cerebral hypoperfusion in clinical for years. However, the exact mechanisms remain unknown. AIM OF THE STUDY: To investigate the effects and mechanisms underlying HLYND-mediated improvement in cognitive deficits associated with chronic cerebral hypoperfusion. MATERIALS AND METHODS: Thirty-six Sprague-Dawley rats were randomly allocated to three groups: sham, model, and HLYND. Daily administration of HLYND or volume-matched vehicle by gavage was initiated 1 day after bilateral carotid artery stenosis (BCAS) and continued for 42 days. The Morris water maze (MWM) test was used to assess cognitive functions from days 36-42. Via western blot and immunofluorescent staining, restoration of neuronal plasticity and remyelination of white matter were evaluated by analyzing the expression profiles of MAP-2, synaptophysin and MBP. In addition, macrophage/microglial activation was assessed by quantifying changes in Iba1, and macrophage/microglial polarization was assessed by changes in iNOS and CD16 (M1 markers), as well as Arg1 and CD206 (M2 markers). RESULTS: In the MWM test, BCAS rats showed significantly extended escape latency and reduced platform crossing times, while those in the HLYND group had shortened escape latency and increased frequency of platform crossing. In addition, rats in the model group showed decreased levels and abnormal morphological changes of MAP-2, synaptophysin and MBP, whereas HLYND administration reversed these effects. As expected, Iba1 levels were elevated in both the model and HLYND groups but rats in the model group showed increased levels of the M1 markers, iNOS and CD16, and a correspondent decrease in the M2 marker, Arg1. In contrast, in the HLYND group, iNOS and CD16 levels were suppressed, while Arg1 levels were elevated. CONCLUSIONS: Our findings demonstrate that HLYND mitigates cognitive impairment after chronic cerebral hypoperfusion in rats through mechanisms involving increased neuronal plasticity and white matter remyelination, with a subtile modulation of macrophage/microglial polarization toward the M2 phenotype.

MEPO promotes neurogenesis and angiogenesis but suppresses gliogenesis in mice with acute ischemic stroke.

Previously study has proved the non-erythropoietic mutant erythropoietin (MEPO) exerted neuroprotective effects against ischemic cerebral injury, with an efficacy similar to that of wild-type EPO. This study investigates its effects on neurogenesis, angiogenesis, and gliogenesis in cerebral ischemic mice. Male C57BL/6 mice were subjected to middle cerebral artery occlusion (MCAO) and reperfusion. EPO (5000 U/kg), MEPO (5000 U/kg) or equal volume of normal saline was injected intraperitoneally. Neurological function was evaluated by Rota-rod test, Neurological severity scores (NSS) and Adhesive removal test. After ischemia and reperfusion (I/R), the survival rate, brain tissue loss, neurogenesis, angiogenesis and gliogenesis were detected by Nissl staining, Immunofluorescence and Western blot, respectively. The results shown that MEPO significantly increased survival rate, reduced brain tissue loss, and improved neurological function after MCAO (P < 0.05). Furthermore, MEPO obviously enhanced the proliferation of neuronal precursors (DCX) and promoted its differentiation into mature neurons (NeuN) (P < 0.05). In addition, compared to normal saline treatment mice, MEPO increased the number of BrdU-positive cells in the cerebral vasculature (P < 0.05). Whereas, MEPO treatment also reduced the numbers of newly generated astrocytes (GFAP) and microglia (Iba1) (P < 0.05). Among all the tests in this study, there was no significant difference between EPO group and MEPO group. Taken together, MEPO promoted the regeneration of neurons and blood vessels in peripheral area of infarction, and suppressed the gliogenesis, thus promoting neurogenesis, improving neurological function and survival rate. Our findings suggest that the MEPO may be a therapeutic drug for ischemic stroke intervention.

Unique MicroRNAs Signature of Lymphocyte of Yang and Yin Syndromes in Acute Ischemic Stroke Patients.

OBJECTIVE: To identify the differentially expressed microRNAs (miRNAs) profiles of yang and yin syndromes in patients with acute ischemic stroke, and to provide the molecular basis of the classification of these two syndrome types in acute ischemic stroke patients. METHODS: A microarray assay was performed to assess the expression pattern of miRNAs in the lymphocyte of acute ischemic stroke patients. Target genes for the deregulated miRNAs were predicated using the online bioinformatic algorithms and functional annotation via Kyoto encyclopedia of genes and genomes pathway analysis for miRNAs predicted targets was carried out. Based on the predicted target genes of differentially expressed miRNAs, the miRNA-gene-network and miRNA-pathway-network were constructed. RESULTS: Yang score based on tongue texture, urine, dejecta, and appearance, etc. showed that clinical symptoms were distinct between yang and yin syndromes. There were significantly higher total leukocyte number and lower total protein level in patients with yang syndrome compared with those in patients with yin syndrome (P<0.05). Comprehensive miRNA analysis identified 36 unique down-regulated miRNAs in yang syndrome group, and 20 unique down-regulated and 2 unique up-regulated miRNAs in yin syndrome group. The key regulatory miRNAs, gene, and pathways in the yang syndrome were hsa-miR-93-5p and -320b, enabled homolog, the metabolic pathways and mitogen-activated protein kinase signaling pathways, respectively, while those in the yin syndrome were hsa-miR-424-5p and -106b-5p, CNOT4, hepatitis B and pathways in cancer, respectively. CONCLUSION: These results offered insight into the molecular basis underlying the different pathogenesis of yang or yin syndrome, providing clues for the individualized therapeutic strategies of acute ischemic stroke.

Assessment of treatment outcomes in patients with advanced hilar cholangiocarcinoma (stages III-IV): Clinical significance of interventional therapy.

The clinical significance of palliative interventional therapy in the management of patients with advanced hilar cholangiocarcinoma (HCCA; stages III-IV) has yet to be studied. The present work was aimed to compare the clinical outcomes of the patients treated with surgery or interventional therapy.A total of 90 patients with advanced HCCA, who admitted Fuyang First People's Hospital from May 2015 to February 2016, were enrolled. Forty-five of them were assigned to the experimental group receiving biliary drainage as the interventional therapy, and the remaining 45 patients were designated as the conventional group receiving radical/palliative surgery. Before and after the treatment total bilirubin from blood was measured. The length of treatment and medical cost were also examined. All patients were followed up for at least 1 year after the treatment.For both the experimental and conventional groups, the serum bilirubin levels after treatment were significantly lower than those before treatment (P < .05); however, no significant differences between groups were seen. There were no significant differences between experimental and conventional groups in the incidence of postoperative complications and survival outcomes. Of note, the length of treatment of the experimental group was substantially shorter than that of the conventional group (P < .05). The medical expense of the experimental group was only about one-third of that of the conventional group (P < .05).Although the interventional therapy does not improve patients' survivals and reduce the incidence of complications, it significantly shortens the treatment length, reducing substantially the medical expense. This finding provides new insights into the treatment strategy for patients with advanced HCCA.

[Effect of anti-androgen and progesterone on development of regrowth antlers in 6 year old sika deer].

To investigate the effects of anti-androgen drugs and melengestrol acetate (MGA) on development of regrowth antlers in 6 year old sika deer, twenty healthysika deerwith similar body weight and antler weightwere randomly divided into five groups by using single factor test design: flutamide (n=4), bicalutamide (n=4), progesterone acetate (CPA, n=4), melengestrol acetate (MGA, n=4), control(n=4). All deer were fed with same diets and were housed outside together in an opened fence of 15 m×30 m with free access to water and feed. Treatment groups were injected subcutaneously sustained-release agents of the four drugs respectively when two-branched antlers were harvested. The control group had no special treatment. In the experiment period of 60 d, blood sampleswere collected for 4 times for each deer. The concentration of testosterone in plasma was tested and analyzed to compare the changes between different groups. Development of regrowth antlers was observed. At the end of the experiment, regrowth antlers were weighted and analyzed. The resultsshowed that the weights of regrowth antlers in treatment groups were significantly greater than those from control group and the weight gain (as compared with the control group) was 100.50%, 64.46%, 87.16% and 117.46% respectively in flutamide group, bicalutamide group, progesterone acetate group and melengestrol acetate group. For plasma testosterone concentration, it was not significantly different in the early stage (in the first 35 d), but at the end of the experimen, it was significantly higher than that of earlier stage (P<0.01) in various groups. Testosterone concentration of flutamide treated group was significantly lower than that of the other groups (P<0.01), while the level inbicalutamide and MGA treated groups was significantly higher than that in other groups (P<0.01). The results showed that both anti-androgen drugs and MGA treatment promoted the development of regrowth antlers and increased the weight of regrowth antlers, where the effect was most significant by MGA treatment. From the morphological observation of the antlers, it was found that anti-androgen and MGA treatments prolonged the growth period of regrowth antlers through delaying the ossification of antlers. However, plasma testosterone concentration was not affected by the treatments.

[Quality evaluation of musk based on the biological potency of its anti-thrombin activty].

This study attempts to establish a method for the anti-thrombin activty bioassay of musk, explore the impact of species and producing areas on the anti-thrombin activty of musk, and provide scientific basis for its biological quality evaluation. Anti-thrombin activty of musk was analyzed by thrombin titration, and the influence factors such as musk solution concentration, fibrinogen concentration, thrombin concentration and titration interval were optimized to evaluate the effect of different species and producing areas on anti-thrombin activty of musk. As a result, there was a good linear relationship between musk solution concentration and thrombin consumption volume within the range of 0.01-0.02 g·mL⁻¹ (r=0.991 4) under the experimental condition as follows: fibrinogen concentration was 0.5%, the thrombin concentration was 10 U·mL⁻¹ï¼› titration time interval was once every minute, and each titration volume was 2 µL. The average anti-thrombin activty potency of Moschus berezovskii from different producing areas was (105.0±10.4) U·g⁻¹, (102.4±5.5) U·g⁻¹ for M. sifanicus from different producing areas, (97.7±6.6) U·g⁻¹ for M. moschiferus from Anhui province, and (58.6±6.4) U·g⁻¹ for artificial musk. The results indicated that this anti-thrombin activty bioassay method could be applied to evaluate the anti-thrombin activty of musk quickly, conveniently, sensitively and exactly. It was also suggested that different species and producing areas had effects on the anti-thrombin activty of musk, so it is necessary to pay attention to species and producing areas in the process of musk domestication; meanwhile, the artificial musk and natural musk also showed great differences in anti-thrombin activty, suggesting that ratio in artificial musk prescription needs to be further optimized.

[Research progress on identification and quality control of Cervi Cornu Pantotrichum].

Cervi Cornu Pantotrichum, as a traditional Chinese medicine, has great potential for development. However, the identification and quality control system is not perfect, leading to the market chaos and chronic slow growth in deep processing of Cervi Cornu Pantotrichum. This paper gives an overview of present situation in identification and quality control system of the Cervi Cornu Pantotrichum, and analyzes present problems. Based on these results, the feasibility study scheme in identification and quality control system for Cervi Cornu Pantotrichum would be then put forward, providing ideas to establish its comprehensive evaluation system.

RRS1 silencing suppresses colorectal cancer cell proliferation and tumorigenesis by inhibiting G2/M progression and angiogenesis.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. Ribosome biogenesis regulatory protein homolog (RRS1) is an essential factor involved in ribosome biogenesis, while its role in CRC remains largely unclear. Here, we found that RRS1 expression was significantly higher in CRC tissues compared with adjacent normal tissues. RRS1 High expression also predicted poor overall survival of CRC patients. Knockdown of RRS1 induced the G2/M cell cycle arrest, apoptosis and suppressed the proliferation of RKO and HCT-116 CRC cells. Furthermore, angiogenesis was also reduced in CRC cells after RRS1 knockdown. In addition, suppression of RRS1 blunted the tumor formation of CRC cells in nude mice. At the molecular level, silencing of RRS1 decreased the expression of M-phase inducer phosphatase 3 (CDC25C), Cyclin-dependent kinase 1 (CDK1), antigen KI-67 (KI67) and increased the protein level of cyclin-dependent kinase inhibitor 1 (CDKN1A) and tumor suppressor p53 (p53). Taken together, our findings provide evidence that RRS1 may promote the development of colon cancer. Therefore, targeting RRS1 may be a promising therapeutic strategy for CRC patients.

Upregulation of RASAL2 promotes proliferation and metastasis, and is targeted by miR-203 in hepatocellular carcinoma.

RAS protein activator like 2 (RASAL2) has been reported to be dysregulated in various types of cancer. It has previously been demonstrated that RASAL2 is hypomethylated in hepatocellular carcinoma (HCC). However, the expression pattern of RASAL2 and its potential role in HCC remain to be elucidated. The present study demonstrated that the expression of RASAL2 was upregulated in HCC tissues, compared with in normal liver tissues, by using immunohistochemistry. In addition, Cell Counting Kit-8 assay and invasion assay revealed that knockdown of RASAL2 inhibited the growth and invasion of HCC cells. Western blotting results indicated that the inhibition of RASAL2 reduced the levels of phosphorylated-AKT. Notably, RASAL2 was observed to be a direct target of miR-203 in HCC in luciferase activity assays. Furthermore, overexpression of miR-203 exhibited a similar effect to RASAL2 knockdown in HCC cells. These results indicated that RASAL2 serves a tumor oncogenic role in HCC and may be considered a potential target in HCC.

Prognostic Value of Red Blood Cell Distribution Width on Bleeding Events in Nonvalvular Atrial Fibrillation Patients Taking Dabigatran (110 mg b.i.d.) after Catheter Ablation.

OBJECTIVES: Recent research has indicated that red blood cell distribution width (RDW) is associated with the prognosis of cardiovascular diseases such as chronic heart failure and coronary heart disease. We aimed to study the predictive value of RDW for bleeding events in patients with nonvalvular atrial fibrillation (NVAF) during the administration of 110 mg of dabigatran twice a day after catheter ablation. METHODS: One hundred and seventy-two NVAF patients who were hospitalized and received catheter ablation in Jiangsu Provincial People's Hospital from January 2014 to January 2015 were enrolled (110 mg of dabigatran was administered orally to outpatients preoperatively twice a day for 3 weeks). The enrolled patients were divided into the high RDW (>12.8%) group (n = 85) and the low RDW (≤12.8%) group (n = 87) according to the median RDW. The activated partial thromboplastin time (APTT) at dabigatran trough concentration was also detected. Patients were followed up for 3 months to observe the occurrence of bleeding events, and the predictive value of RDW as well as APTT for bleeding events was assessed from receiver-operating characteristic (ROC) analyses. RESULTS: In all patients, preoperatively, no bleeding events were observed and the APTT did not exceed twice the normal upper limit. Thirteen cases of bleeding events, all minor bleeding, occurred after a 3-month follow-up: 3 of gingival bleeding, 3 of urinary tract bleeding, 3 conjunctival hemorrhages and 4 subcutaneous hemorrhages. The incidence of bleeding events in the low RDW group was lower than in the high RDW group (3.4 vs. 11.8%, p = 0.039). The areas under the ROC curve for RDW and APTT to predict the occurrence of bleeding events were 0.737 (cutoff point 13.25%; p < 0.05) and 0.558 (p > 0.05), respectively. CONCLUSION: RDW was associated with the occurrence of bleeding events in NVAF patients on dabigatran (110 mg twice a day) after ablation, while also being an independent predictor of bleeding events. RDW had superior predictive value for bleeding events over APTT when APTT did not exceed twice the normal upper limit.

Effect of dietary choline levels on growth performance, lipid deposition and metabolism in juvenile yellow catfish Pelteobagrus fulvidraco.

The present experiment was conducted to determine the effect and mechanism of dietary choline levels on growth performance and lipid deposition of yellow catfish Pelteobagrus fulvidraco. Dietary choline was included at three levels of 239.2 (control (without extra choline addition), 1156.4 and 2273.6mg choline per kg diet, respectively) and fed to yellow catfish (mean initial weight: 3.45±0.02g mean±standard errors of mean (SEM)) for 8weeks. Fish fed the diet containing 1156.4mgkg-1 choline showed the higher weight gain (WG), specific growth rate (SGR) and feed intake (FI), but the lower feed conversion rate (FCR), than those in control and highest choline group. Hepatosomatic index (HSI) and hepatic lipid content declined with increasing dietary choline levels. Muscle lipid content was the lowest for fish fed adequate choline diets and showed no significant difference between other two groups. Choline contents in liver and muscle increased with increasing dietary choline levels. Dietary choline levels significantly influenced mRNA levels of genes involved in lipid homeostasis in muscle and liver, such as CTP:phosphocholine cytidylyltransferase a (CCTa), phosphatidylethanolamine N-methyl-transferase (PEMT), microsomal triglyceride transfer protein (MTP), apolipoprotein b (APOBb), apolipoprotein E (ApoE) and lipoprotein lipase (LPL), and effects of dietary choline levels on lipid deposition and metabolism were tissue-specific. Different responses of these genes at the mRNA levels partially explained the profiles of lipid deposition in liver and muscle for fish fed different choline diets. To our knowledge, this is the first to explore the effect of dietary choline level on mRNA expression of these genes, which provides new insights into choline nutrition in fish.