GSK2795039 prevents RIP1-RIP3-MLKL-mediated cardiomyocyte necroptosis in doxorubicin-induced heart failure through inhibition of NADPH oxidase-derived oxidative stress.

Doxorubicin (DOX), which is widely used for the treatment of cancer, induces cardiomyopathy associated with NADPH oxidase-derived reactive oxygen species. GSK2795039 is a novel small molecular NADPH oxidase 2 (Nox2) inhibitor. In this study, we investigated whether GSK2795039 prevents receptor-interacting protein kinase 1 (RIP1)-RIP3-mixed lineage kinase domain-like protein (MLKL)-mediated cardiomyocyte necroptosis in DOX-induced heart failure through NADPH oxidase inhibition. Eight-week old mice were randomly divided into 4 groups: control, GSK2795039, DOX and DOX plus GSK2795039. H9C2 cardiomyocytes were treated with DOX and GSK2795039. In DOX-treated mice, the survival rate was reduced, left ventricular (LV) end-systolic dimension was increased and LV fractional shortening was decreased, and these alterations were attenuated by the GSK2795039 treatment. GSK2795039 inhibited not only myocardial NADPH oxidase subunit gp91phox (Nox2) protein, but also p22phox, p47phox and p67phox proteins and prevented oxidative stress 8-hydroxy-2'-deoxyguanosine levels in DOX-treated mice. RIP3 protein and phosphorylated RIP1 (p-RIP1), p-RIP3 and p-MLKL proteins, reflective of their respective kinase activities, markers of necroptosis, were markedly increased in DOX-treated mice, and the increases were prevented by GSK2795039. GSK2795039 prevented the increases in serum lactate dehydrogenase and myocardial fibrosis in DOX-treated mice. Similarly, in DOX-treated cardiomyocytes, GSK2795039 improved cell viability, attenuated apoptosis and necrosis and prevented the increases in p-RIP1, p-RIP3 and p-MLKL expression. In conclusion, GSK2795039 prevents RIP1-RIP3-MLKL-mediated cardiomyocyte necroptosis through inhibition of NADPH oxidase-derived oxidative stress, leading to the improvement of myocardial remodeling and function in DOX-induced heart failure. These findings suggest that GSK2795039 may have implications for the treatment of DOX-induced cardiomyopathy.

Reduced circulating Tregs and positive pANCA were robustly associated with the occurrence of antiphospholipid syndrome in patients with systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a typical chronic immune disorder with clinical heterogeneity. The systemic abnormal immune response not only challenges the diagnosis and treatment of the disease itself but also the secondary antiphospholipid syndrome (APS), characterized by recurrent arterial or venous thrombosis, recurrent spontaneous abortion, or stillbirth. Clinical interest has primarily focused on primary APS's pathological and clinical features. However, differences in clinical features and laboratory indicators between SLE with or without APS are still lacking, especially differences between circulating lymphocytes, which are critical in the pathogenesis of SLE and its complications. METHODS: In this retrospective study, we collected and analyzed clinical characteristics, general laboratory indicators, immunological indicators, and circulating lymphocyte subsets of SLE with or without APS. RESULTS: Systemic lupus erythematosus with APS (SLE-APS) had elevated SLEDAI scores, hospitalization costs and time, and frequencies of central nervous system symptoms and spontaneous abortion compared with those without APS. SLE-APS had higher positive anti-Cardiolipin antibodies, anti-ß2 Glycoprotein 1 antibodies, and perinuclear antineutrophil cytoplasmic antibody (pANCA) than none-APS patients. Compared with healthy controls (HCs), the circulating lymphocyte subsets were altered to some extent in all patients, especially in patients with SLE-APS. Reduced Tregs and positive pANCA were independent risk factors for SLE secondary APS. CONCLUSION: The present study revealed a robust association between APS secondary to SLE and reduced Tregs and positive pANCA, which provides essential information regarding the diagnosis and therapeutic possibilities of APS secondary to SLE.

Microbe community composition differences of hand skin on similar lifestyle volunteers: a small-scale study.

AIMS: Human skin is the first barrier against pathogens and environmental hazards and the highest contact frequency occurs with the hands. Environmental and personal metabolic factors may affect skin microbes. This study was conducted to clarify the diversity in the skin microbial community that was mainly due to individual skin metabolites rather than lifestyle and environmental factors. METHODS AND RESULTS: Skin microbiota samples were collected from 11 volunteers who met similar lifestyle inclusion criteria. The V3-V4 region of the 16S rRNA gene was amplified. After library construction and sequencing, we compared the composition and diversity of the hand skin microbiota in different sexes and BMI groups with bioinformation analysis. The whole sequence data were annotated as 42 phyla, 538 families, and 1215 genera. Four dominant phyla accounted for 97% of the total including Actinobacteriota (50.18%), Firmicutes (23.85%), Proteobacteria (21.64%) and Bacteroidota (2.05%). The genera that were detected in all subjects with high relative abundance were Cutibacterium, Staphylococcus, Corynebacterium, Streptococcus, Lawsonella, Enhydrobacter, Escherichia-Shigella, Asaia and Micrococcus. CONCLUSIONS: The diversity and richness of the microbiota of male hand skin in our study was higher than that of females. Interestingly, Cutibacterium, Staphylococcus, and Corynebacterium might serve as important skin microbiota to distinguish sexes.

Serum Sphingosine-1-phosphate level and peritonitis in peritoneal dialysis patients.

BACKGROUND: Given the important role of Sphingosine-1-phosphate (S1P) in maintaining the hemostasis in intestinal barrier function and regulation of inflammation and immune, we hypothesize that S1P might be a biomarker to predict peritonitis in peritoneal dialysis (PD) patients. METHODS: In this case-control study, 78 stable, continuous ambulatory peritoneal dialysis patients were enrolled and followed for the episode of PD associated peritonitis. Patients were divided into two groups by whether or not they had peritonitis during follow-up: non-peritonitis (n = 65) and peritonitis (n = 13) group. S1P was analyzed by enzyme-linked immunosorbent assay. Logistic regression analysis was used to assess factors associated with peritonitis. The variables identified by univariable regression models (p < 0.1) were further selected into the multivariable logistic regression model to determine whether they could independently affect peritonitis. RESULTS: Patients with peritonitis had a lower level of S1P than that of patients without peritonitis (1.3 ng/mL IQ 0.8, 3.6 ng/mL vs. 2.8 ng/mL IQ 1.5, 5.4 ng/mL, p = 0.018). The peritonitis group had lower serum albumin, lower blood leukocyte, lower hemoglobin and lower platelet count as compared to the non-peritonitis group. Logistic regression analysis showed that S1P (OR = 0.381, 95% CI = 0.171-0.848, p = 0.018), blood leukocyte count (OR = 0.438, 95% CI = 0.207-0.925, p = 0.030), and serum albumin (OR = 0.732, 95% CI = 0.556-0.962, p = 0.025) were independent factors associated with peritonitis in the present PD population. CONCLUSION: Our study showed that S1P was an independent determinant of subsequent peritonitis in PD patients. S1P might serve as a biomarker to predict peritonitis in PD patients.

NADPH oxidase 2 inhibitor GSK2795039 prevents doxorubicin-induced cardiac atrophy by attenuating cardiac sympathetic nerve terminal abnormalities and myocyte autophagy.

Doxorubicin is widely used for the treatment of human cancer, but its clinical use is limited by a cumulative dose-dependent cardiotoxicity. However, the mechanism of doxorubicin-induced cardiac atrophy and failure remains to be fully understood. In this study, we tested whether the specific NADPH oxidase 2 (Nox2) inhibitor GSK2795039 attenuates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy, leading to the amelioration of cardiac atrophy and dysfunction in chronic doxorubicin-induced cardiomyopathy. Mice were randomized to receive saline, doxorubicin (2.5 mg/kg, every other day, 6 times) or doxorubicin plus GSK2795039 (2.5 mg/kg, twice a day, 9 weeks). Left ventricular (LV) total wall thickness and LV ejection fraction were decreased in doxorubicin-treated mice compared with saline-treated mice and the decreases were prevented by the treatment of the specific Nox2 inhibitor GSK2795039. The ratio of total heart weight to tibia length and myocyte cross-sectional area were decreased in doxorubicin-treated mice, and the decreases were attenuated by the GSK2795039 treatment. In doxorubicin-treated mice, myocardial Nox2 and 4-hydroxynonenal levels were increased, myocardial expression of GAP43, tyrosine hydroxylase and norepinephrine transporter, markers of sympathetic nerve terminals, was decreased, and these changes were prevented by the GSK2795039 treatment. The ratio of LC3 II/I, a marker of autophagy, and Atg5, Atg12 and Atg12-Atg5 conjugate proteins were increased in doxorubicin-treated mice, and the increases were attenuated by the GSK2795039 treatment. These findings suggest that inhibition of Nox2 by GSK2795039 attenuates cardiac sympathetic nerve terminal abnormalities and myocyte autophagy, thereby ameliorating cardiac atrophy and dysfunction after chronic doxorubicin treatment.

Morbidity and risk factors for surgical site infection following cesarean section in Guangdong Province, China.

AIM: To estimate the incidence of and identify the risk factors for a surgical site infection after a cesarean section. METHOD: A survey of women who underwent a cesarean section was conducted in eight hospitals in Guangdong Province, China. The rate of surgical site infection was estimated and a nested case control study was then carried out to identify the risk factors. RESULTS: Among 13 798 women surveyed, 96 (0.7%) developed a surgical site infection after a cesarean section. Multivariate logistic regression analysis identified six factors independently associated with an increased risk of surgical site infection, which included obesity, premature rupture of membranes, lower preoperative hemoglobin, prolonged surgery, lack of prophylactic antibiotics and excessive anal examinations performed during hospitalization. CONCLUSION: Surgical site infection occurs in approximately 0.7% of cesarean section cases in the general obstetric population in China. Obesity, premature rupture of membranes, lower preoperative hemoglobin, prolonged surgery, lack of prophylactic antibiotics and excessive anal examinations during hospitalization are considered to be independent risk factors.

[Factors influencing the quality of life of elderly living in a pre-fabricated housing complex in the Sichuan earthquake area].

BACKGROUND: The 2008 Sichuan Earthquake caused great damage to the environment and property. In the aftermath, many citizens were relocated to live in newly constructed prefabricated (prefab) communities. PURPOSE: This paper explored the current quality of life (QOL) of elderly residents living in prefabricated communities in areas damaged by the Sichuan earthquake and identified factors of influence on QOL values. The ultimate objective was to provide evidence-based guidance for heath improvement measures. METHODS: The authors used the short form WHOQOL-BREF to assess the quality of life of 191 elderly residents of prefabricated communities in the Sichuan Province 2008 earthquake zone. A Student's t-test, variance analysis, and stepwise multivariate regression methods were used to test the impact of various factors on QOL. RESULTS: Results indicate the self-assessed QOL of participants as good, although scores in the physical (average 56.2) and psychological (average 45.7) domains were significantly lower than the norm in China. Marital status, capital loss in the earthquake, number of children, level of perceived stress, income, interest, and family harmony each correlated with at least one of the short form WHOQOL-BREF domains in t-test and one-way analyses. After excluding for factor interaction effects using multivariate regression, we found interest, family harmony, monthly income and stress to be significant predictors of physical domain QOL, explaining 13.8% of total variance. Family harmony and interest explained 15.3% of total variance for psychological domain QOL; stress, marital status, family harmony, capital loss in the earthquake, number of children and interest explained 19.5% of total variance for social domain QOL; and stress, family harmony and interest explained 16.5% of total variance for environmental domain QOL. Family harmony and interest were significant factors across all domains, while others influenced a smaller proportion. CONCLUSIONS: Quality of life for elderly living in prefab communities should be improved. The authors hope study findings will increase awareness among healthcare providers regarding the quality of life of this vulnerable population. Study results suggest that key steps to promoting QOL in this population include improving family harmony, helping to cultivate well-rounded interests, alleviating economic stresses, providing necessary medical and psychological counseling services, and affording more social support.

Circulating Th2 cell reduction and Th1/Th2 imbalance are correlated with primary Sjogren's syndrome-associated interstitial lung disease.

OBJECTIVE: Primary Sjogren's syndrome (pSS) is a heterogeneous chronic autoimmune disorder characterized by lymphocyte infiltration of the exocrine glands and the involvement and dysfunction of multiple organs and tissues. Interstitial lung disease (ILD) is the most common type of respiratory system damage. This study ascertained the factors related to ILD in patients with pSS (pSS-ILD), such as altered levels of circulating lymphocyte subtypes. METHODS: Eighty healthy controls and 142 patients diagnosed with pSS were included. The pSS patients were classified into groups with pSS-ILD or pSS without ILD (pSS-non-ILD). Baseline clinical and laboratory data were collected for all subjects, including the levels of lymphocytes measured by modified flow cytometry. RESULTS: The pSS-ILD patients were older, had higher ESSDAI scores, had higher positivity rates for anti-SSB and anti-Ro52 antibodies, and had more frequent symptoms of respiratory system involvement than pSS-non-ILD patients. pSS-ILD patients had the lowest Th2 cell counts among the three groups. Although the absolute numbers of Treg and NK cells were lower in pSS patients with and without ILD than in the healthy controls, there was no significant difference between the two pSS groups. The Th1/Th2 ratio was significantly higher in patients with ILD than in patients without ILD. Further analysis showed that older age (OR=1.084), lower Th2 count (OR=0.947), higher Th1/Th2 ratio (OR=1.021), and positivity for anti-SSB (OR=3.620) and anti-Ro52 (OR=5.184) antibodies were associated with the occurrence of ILD in patients with pSS. CONCLUSION: Decreased circulating Th2 cells and an elevated Th1/Th2 ratio may be the immunological mechanism underlying the development of ILD in pSS patients.

Berberine and Ginsenoside Rb1 Ameliorate Depression-Like Behavior in Diabetic Rats.

Rhizoma coptidis (Huang-lian) and Asian ginseng have been widely used in the treatment of diabetes and other concurrent diseases with apparent effects. This study investigated the effects of the active ingredients of R. coptidis and ginseng, berberine and ginsenoside Rb1, on depression-like behavior in a rat diabetes model. The animal model was established via a high-fat diet and intraperitoneal injection of streptozotocin, while the animal's depression-like behavior was induced via chronic unpredictable mild stress. These experimental rats were divided into four groups: control, depression-like behavior (DLB), metformin plus fluoxetine hydrochloride (M+FH), and berberine plus ginsenoside Rb1 (B+GRb1) groups. Glucose metabolism and insulin resistance were evaluated by oral glucose test and glucose clamp study. Depression-like behavior was evaluated via behavioral analyses, including forced swim, sucrose preference, elevated plus maze, and open-field tests. HE and Nissl staining, plasma cortisol expression of adrenocorticotropic hormone, and brain-derived neurotrophic factor (BDNF) levels were assayed to explore the mechanisms of action. Compared with the control, rats in the DLB group had a significant increase in the levels of blood glucose and depression-like behavior. The B+GRb1 group significantly improved glucose metabolism and insulin resistance, reduced depression-like behavior, downregulated levels of plasma cortisol and adrenocorticotropic hormone under stress, and upregulated BDNF protein expression compared to the DLB rats. HE and Nissl staining data revealed that B+GRb1 protected neurons from pathological and morphological changes. Thus, berberine and ginsenoside Rb1 not only improved glucose metabolism in diabetic rats but also ameliorated their depression-like behavior under chronic unpredictable stress. Mechanistically, studied data with plasma hormonal levels and brain neuronal pathological/morphological changes supported the observed effects. The combination of berberine and ginsenoside Rb1 may have a clinical value in the management of diabetic patients with depression.

Strategies and criteria targeting the reform and development for the teaching resource of nursing undergraduate: A multi-center cross-sectional study.

ABSTRACT: Teaching resource of nursing students play an important role in improving clinical performance, while there is a little know and dearth of the access and development criteria or guidance of teaching resources for nursing undergraduates.To develop the admission and development criteria of education resources for nursing undergraduates, and to explore and determine its composition and connotation.A cross-sectional survey has been used.A total of 22 Chinese nursing schools and affiliated teaching bases (hospitals and community health centers).A total of 20 nursing experts were consulted to develop the questionnaire of admission and development criteria of teaching resource for nursing undergraduates in China, and then 285 valid experts from 22 Chinese nursing schools and affiliated teaching bases (hospitals and community health centers) conducted the questionnaire survey to evaluate experts' consensus rate and view on the composition and connotation of the developed criteria.There were 6 domains and 43 items included in the admission and development criteria of teaching resource for nursing undergraduates, which domains included educational budget and allocation of resources, infrastructure, clinical teaching bases, books and information services, educational experts, and educational exchanges. The experts' consensus rate was more than 90.2%.The standard is helpful to guide the future admission and development of teaching resource for nursing undergraduates, and favor the education quality improvement of nursing undergraduates.

Effects of Berberine on Diabetes and Cognitive Impairment in an Animal Model: The Mechanisms of Action.

Diabetes is a group of metabolic disorders with an increased risk of developing cognitive impairment and dementia. The hippocampus in the forebrain contains an abundance of insulin receptors related to cognitive function and plays an important role in the pathophysiology of neurodegenerative disorders. Berberine from traditional Chinese medicine has been used to treat diabetes and diabetic cognitive impairment, although its related mechanisms are largely unknown. In this study, a STZ diabetes rat model feeding with a high-fat diet was used to test the effects of berberine compared with metformin. Oral glucose tolerance and hyperinsulinemic-euglycemic clamp were used for glucose metabolism and insulin resistance. The Morris water maze was used to observe the compound effects on cognitive impairment. Serum and hippocampal [Formula: see text]-amyloid peptide (A[Formula: see text], Tau and phosphorylated Tau protein deposition in the hippocampi were measured. The TUNEL assay was used to detect the neuronal apoptosis, supported by histomorphological changes and transmissional electron microscopy (TEM) image. Our data showed that the diabetic rats had a significantly cognitive impairment. In addition to improving glucose metabolism and reducing insulin resistance, berberine significantly improved the cognitive function in the rat. Berberine also effectively decreased the expression of hippocampal tau protein, phosphorylated Tau, and increased insulin receptor antibodies. Moreover, berberine downregulated the abnormal phosphorylation of A[Formula: see text] and Tau protein and improved hippocampal insulin signaling. The TUNEL assay confirmed that berberine reduced hippocampal neuronal apoptosis supported by TEM. Thus, berberine significantly improved the cognitive function in diabetic rats by changing the peripheral and central insulin resistance. The reduction of neuronal injury, A[Formula: see text] deposition, abnormal phosphorylation of Tau protein, and neuronal apoptosis in the hippocampus were observed as the related mechanisms of action.

Study on quantitative diagnosis model of TCM syndromes of post-stroke depression based on combination of disease and syndrome.

BACKGROUND: Post-stroke depression (PSD) is one of the most common stroke complications with high morbidity. Researchers have done much clinical research on Traditional Chinese Medicine (TCM) treatment, but very little research on diagnosis. Based on the thought of combination of disease and syndrome, this study will establish a unified and objective quantitative diagnosis model of TCM syndromes of PSD, so as to improve the clinical diagnosis and treatment of PSD. OBJECTIVE: First: To establish a unified and objective quantitative diagnosis model of TCM syndromes in PSD under different disease courses, and identify the corresponding main, secondary, and concurrent symptoms, which are based on the weighting factor of each TCM symptom. Second: To find out the relationship between different stages of PSD and TCM syndromes. Clarify the main syndrome types of PSD under different stages of disease. Reveal the evolution and progression mechanism of TCM syndromes of PSD. METHODS AND ANALYSIS: This is a retrospective study of PSD TCM diagnosis. Three hundred patients who were hospitalized in the First Teaching Hospital of Tianjin University of TCM with complete cases from January 2014 to January 2019 are planned to be recruited. The study will mainly collect the diagnostic information from the cases, find the related indicators of TCM and Western medicine in PSD, and clarify the relationship between different disease stages and TCM syndromes. Finally, the PSD TCM syndrome quantitative diagnosis model will be established based on the operation principle of Back Propagation (BP) artificial neural network. CONCLUSION: To collect sufficient medical records and establish models to speed up the process of TCM diagnosis.

Compartmentalization and delivery via asymmetric copolymer monolayers with swollen or inverse swollen micelles.

We investigate the equilibrium properties and the underlying dynamics of emulsions formed in asymmetric A-B copolymers in matrices of immiscible B and C molecular fluids using coarse-grained molecular dynamics simulations. The emulsions are generated by introducing net attractions among the A units of the copolymers and the C molecules. They coexist with an absorbed copolymer monolayer. We determine the interfacial properties as the emulsions are forming. In general, highly asymmetric copolymers self-assemble within the B-matrix phase into swollen micelles; the cores of which are composed of C-component material. Less asymmetric copolymers, however, after initially budding and eventually fissioning from the interfacial copolymer monolayer, generate emulsified "inverse swollen micelles" within the C-matrix phase. These stable inverse (crew-cut) swollen micelles, which form under the inward bending of the saturated or oversaturated interfaces toward the longer B-block due to the attraction between the A and C units, can encapsulate large amounts of B-matrix component in their cores. This monolayer collapse mechanism can be exploited to generate nanoreactors or containers that enhance the delivery of molecular components into immiscible molecular fluid environments.

Increases in tumor markers are associated with primary Sjögren's syndrome-associated interstitial lung disease.

AIMS: Interstitial lung disease (ILD) is the most common type of pulmonary involvement of extraglandular complication in patients with primary Sjögren's syndrome (pSS), but the diagnosis of pSS-associated ILD (pSS-ILD) is still challenging. This study aimed to investigate the levels of serum tumor markers in pSS patients with or without ILD (pSS-non-ILD) and explore its diagnostic value for pSS-ILD. METHODS: A total of 168 pSS-ILD patients and age- and sex-matched 538 pSS-non-ILD were recruited. The levels of peripheral tumor markers, including carbohydrate antigen (CA)153, CA125, CA19-9, carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), ß-human chorionic gonadotropin, alpha fetoprotein, CA724, and complexed prostate specific antigen, the clinical manifestations, and general laboratory indicators were measured and collected. RESULTS: Compared with pSS-non-ILD, pSS-ILD patients had higher levels of disease activity indicators, such as EULAR Sjögren's syndrome disease activity index, ESR, and CRP, and elevated serum levels of tumor markers: NSE, CEA, CA125, and CA153. The serum levels of CA153 [odds ratio (OR) = 4.521, 95% confidence interval (CI) = [1.871, 10.928)] and CEA [OR = 2.879, 95% CI = (1.305, 6.353)] were significantly correlated with the onset of SS-ILD. CA153 was the only tumor marker with area under receiver operating characteristic curve (AUC) over 0.7 [AUC = 0.743, 95% CI = (0.70, 0.79)]. CONCLUSION: Tumor markers increased in serum of pSS-ILD patients. Higher CA153 levels are significantly correlated to the increased risk of ILD in patients with pSS and may be directly involved in the pathogenesis of pSS-ILD. Serum CA153 had the best diagnostic value in those tumor markers for pSS-ILD without malignancy.

Correlation between self-perceived burden and self-management behavior in elderly stroke survivors: A longitudinal observational study.

The aim of this study was to assess the levels of self-perceived burden (SPB) and self-management behavior in elderly stroke survivors during the first 3 months after acute stroke, and to explore the correlation between them.A total of 203 consecutive hospitalized elderly patients diagnosed with stroke were recruited. Self-perceived Burden Scale and Stroke Self-management Scale in 1 month (T1) and 3 months (T2) post-stroke were assessed and compared.The score of SPB in elderly stroke survivors was 28.96 ±â€Š5.50 and 27.25 ±â€Š6.17 at T1 and T2, respectively. Stroke self-management scale scored 165.93 ±â€Š9.82 at T1 and 167.29 ±â€Š10.60 at T2. In the first 3 months post-stroke, the physical burden was dominant (T1 14.73 ±â€Š3.07, T2 14.40 ±â€Š3.13), and the behavior of stroke symptoms and signs monitoring (T1 27.58 ±â€Š6.56, T2 28.64 ±â€Š6.43) and rehabilitation exercise management (T1 21.40 ±â€Š3.28, T2 20.74 ±â€Š3.15) was the worst. SPB was negatively correlated with self-management behavior (T1 r = -.202, T2 r = -.511).Elderly stroke survivors experienced a medium level of SPB and self-management behavior in the first 3 months post-stroke. There is a positive relationship between reduced SPB and improved self-management behavior. Addressing the characteristics and correlations as well as development of targeted interventions for SPB decreasing is beneficial to improving self-management behavior for elderly survivors.

miR-181a promotes porcine granulosa cell apoptosis by targeting TGFBR1 via the activin signaling pathway.

Activin/Smad3 signaling plays a pivotal role in follicle development and atresia. However, the precise mechanisms underlying this process are not yet fully understood. Herein, we identified miR-181a as a central component of activin/Smad3-mediated follicle atresia. miR-181a was strikingly upregulated in porcine atretic follicles, which induced the apoptosis of porcine granulosa cells (GCs) in vitro. Furthermore, the transforming growth factor-ß type 1 receptor (TGFBR1) was confirmed as a direct target of miR-181a by bioinformatics analysis and luciferase assays. Transfection with an miR-181a agomir repressed the TGFBR1 mRNA and protein levels. In addition, TGFBR1 overexpression repressed GC apoptosis, whereas TGFBR1 inhibition promoted GC apoptosis. miR-181a overexpression downregulated the phosphorylation of Smad3 and blocked the activation of TGF-ß signaling. Moreover, activin A downregulated miR-181a expression and upregulated the TGFBR1 and p-Smad3 protein levels. Collectively, these data suggest that miR-181a regulates porcine GC apoptosis by targeting TGFBR1 via the activin signaling pathway.

Long-term baicalin administration ameliorates metabolic disorders and hepatic steatosis in rats given a high-fat diet.

AIM: Baicalin, one of the major flavonoids in Scutellaria baicalensis, possesses antioxidant and anti-inflammatory properties. However, the effects of baicalin on metabolic disorders and hepatic steatosis have not been investigated. METHODS: Body weight was examined in high-fat diet (HFD)-fed rats with or without baicalin treatment. At the end of the experiment, serum biochemical parameters, liver histology and lipid profile were analyzed to assess whether the animals were suffering from metabolic disorders or hepatic steatosis. In the liver, the phosphorylation of AMP activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) and the gene expression of some enzymes involved in lipogenesis were examined. The effects of baicalin on the phosphorylation of AMPK and lipid accumulation induced by high glucose in human hepatoma HepG2 cells were also examined. RESULTS: Baicalin (80 mg/kg) administered ip for 16 weeks suppressed body weight gain in HFD-fed rats. Weight reduction was accompanied by the reduction of visceral fat mass. Baicalin significantly decreased the elevated serum cholesterol, free fatty acid and insulin concentrations caused by the HFD. Baicalin also suppressed systemic inflammation by reducing the serum level of tumor necrosis factor alpha. Baicalin reduced hepatic lipid accumulation, enhanced the phosphorylation of AMPK and ACC and down-regulated genes involved in lipogenesis, including fatty acid synthase and its upstream regulator SREBP-1c. In HepG2 cells, baicalin (5 and 10 micromol/L) increased the phosphorylation of AMPK and decreased lipid accumulation following the addition of high glucose. CONCLUSION: Our study suggests that baicalin might have beneficial effects on the development of hepatic steatosis and obesity-related disorders by targeting the hepatic AMPK.

Three-dimensional reconstruction of the uterine vascular supply through vascular casting and thin slice computed tomography scanning.

It was the objective of this study to construct a model of the uterine vascular supply through vascular casting and thin slice computed tomography scanning. This will provide a teaching aide for the understanding of uterine artery embolization (UAE) procedures, as well as normal uterine and ovarian arterial anatomy. Using 20% chlorinated poly vinyl chloride, we infused and cast a set of a normal uterus, vagina and bilateral adnexa through the uterine artery and ovarian artery. After thin slice CT scanning, we obtained the three-dimensional (3D) reconstruction by maximum intensity projection (MIP) and surface-shaded display (SSD), and then observed its figure and characteristics. A model of the uterine vascular supply can be successfully reconstructed by vascular casting and thin slice CT scanning. The 3D reconstruction offers a clear view of the course of the uterine artery and its blood supply distribution. It has two major branches: The intramuscular uterine branch and the cervicovaginal branch (1). Blood supply is generally unilateral, with communicating branches between the two sides and possible anastomoses between the arterial blood supply of the uterus and the ovaries. The major blood supply of the cervix comes from the cervicovaginal branch of the uterine artery, while the vaginal arterial supply derives directly from the internal iliac artery. The CT technique allows real-time 360 degrees rotation and changes in model for in-depth study of the vascular network and its adjacent tissues. It is possible to construct an in vitro uterine arterial network by vascular casting and CT scanning, which can provide unique insight into the female genitourinary system arterial network. Based on this, we can create reconstructions as well as models for different diseases such as leiomyomata, adenomyosis, and endometrial cancer. These models will provide morphological evidence to the interventional therapy and UAE teaching in Obstetrics and Gynecology.

[A study on the psychological state of nurse-students of a university in affected areas of Wenchuan earthquake].

BACKGROUND: The 8.0-magnitude earthquake that struck Wenchuan County in Sichuan was the most destructive earthquake to hit China since the People's Republic of China was founded in 1949. It caused great environmental harm and property damage, and brought considerable psychological stress and emotional problems to many in the population. PURPOSE: This study was designed to investigate the psychological state of nursing students studying at a university located within the Wenchuan earthquake zone. METHODS: Nurses were recruited using a striated cluster sampling approach. The study was conducted using a self-designed questionnaire, Self-Rating Depression Scale (SDS), Self-Rating Anxiety Scale (SAS), Social Support Rating Scale (SSRS) and Coping Style Questionnaire. RESULTS: Most (68.8%) participants lacked sufficient knowledge regarding the earthquake, and the social support condition of college nursing students was lower than the population average (p < .001). However, degree of anxiety and depression was higher than the population average (p < .001). SSRS scores and its three dimensions were positively correlated with SAS scores and negatively correlated with SDS scores (p < .001). Participants most often employed basic problem solving approaches to deal with psychological conflicts arising from their earthquake experience. No significant difference between nursing students in different class years in terms of study variables was identified. CONCLUSION: Nursing students in areas affected by the Wenchuan earthquake suffer from anxiety and depression disorders. Adequate social support represents an important intervention needed to maintain and enhance their mental health.

Potential urine biomarkers for gestational hypertension and preeclampsia.

Differential proteomic technology was used to identify urine proteomic profile of gestational hypertension and preeclampsia. Urine samples were collected from 10 patients with gestational hypertension, 10 patients with mild preeclampsia, 10 patients with severe preeclampsia and 10 normal pregnancies and analyzed by 2­D difference gel electrophoresis, then matrix assisted laser desorption ionization mass spectrometry was used to identify differential proteins. Subsequently, ELISA was used to verify the content variation of the identified proteins in 200 urine samples. In total, 30 differential proteins were identified. For prostaglandin­H2 D­isomerase (L­PGDS), perlecan and other 15 proteins, the contents in patients with gestational hypertension were higher than that of normal pregnancies, but lower in mild and severe preeclampsia. By contrast, serum albumin and α­1­antitrypsin was lower in samples from patients with gestational hypertension and higher in patients with mild and severe preeclampsia compared with normal pregnancies. ELISA verified that the urinary concentration of L­PGDS and perlecan were significantly lower in patients with preeclampsia than in normal pregnancies (P<0.05). Urine proteomics is a useful tool to identify potential biomarkers to distinguish between different types of hypertensive disorders in pregnancy. L­PGDS and perlecan could potentially be used as markers to reflect the state of renal function, and may participate in the genesis and development of renal injury during preeclampsia.