Regulation of Osteosarcoma Cell Proliferation, Migration, and Invasion by miR-143 and miR-199a Through COX-2 Targeting.

Objective: To investigate the biological role of miR-143 and miR-199a in mediating the progression of osteosarcoma (OS) by targeting cyclooxygenase (COX-2). Introduction: COX-2 plays a crucial role in the development and progression of OS. However, the specific regulatory mechanisms of COX-2 in OS are still not well understood. Methods: The expression levels of COX-2, miR-143 and miR-199a in OS tissues were detected using immunohistochemistry, qPCR, or western blot assays. The targeting relationship between miRNAs and COX-2 was determined. The effect of miRNA and COX-2 on OS cells was evaluated in vitro and in vivo. Results: COX-2 expression was upregulated while miR-143 and miR-199a were downregulated in OS tissues. miR-143 and miR-199a suppressed the proliferation, migration, and invasion of OS cells. The dual-luciferase reporter gene assay showed that COX-2 was a direct target of miR-143 and miR-199a. Genetic knockdown of COX-2 significantly suppressed cell proliferation, induced apoptosis, and inhibited migration and invasion of OS cells. The expression levels of COX-2 and PGE2 were decreased after the overexpression of miR-143 and miR-199a. Additionally, COX-2 silencing inhibited the tumorigenesis of OS and the synthesis of PGE2 in vivo. Conclusions: miR-143 and miR-199a/COX-2 axis modulates the proliferation, invasion, and migration in osteosarcoma.

Effects of Body Weight and Waist Circumference on Balance Function in Overweight and Obese Adults / 中山大学学报(医学科学版)

ObjectiveTo explore the effects of body weight and waist circumference on static and dynamic balance function in overweight and obese adults. MethodsParticipants （n=103） were selected by cluster random sampling from the Hypoglycemic Weight Loss Clinic of the Endocrinology Department of the Third Affiliated Hospital of Sun Yat-sen University. All participants were assessed for basic data collection， biochemical test， body weight， waist circumference and height measurement， static balance function assessed by balance error scoring system （BESS） and dynamic balance function assessed by functional reach test （FRT）. The BESS score and FRT distance of all participants were compared among groups according to different BMI grades and WC grades. Multivariate linear regression was used to analyze the influencing factors of participants' dynamic and static balance functions. Results① With the increase of BMI grading， the BESS score showed an upward trend， and the difference between groups was statistically significant （P = 0.004）. The BESS score of normal WC patients was lower than that of central obesity patients （P < 0.001）， which indicated that compared with normal BMI， overweight and obese people had poor dynamic and static balance ability； ② With the BMI grading， the FRT distance increased， showing a downward trend （P < 0.001）. The FRT distance in normal WC patients was significantly higher than that in central obesity patients （P < 0.001）， which indicated that the static and dynamic balance ability of central obesity patients was worse than that of normal WC patients； ③ In BMI overweight group， the FRT distance decreased significantly with the increase of WC （P = 0.02）. The results showed that under the condition of no difference in BMI， Compared with normal WC， the dynamic and static balance ability of central obese patients was worse； ④ The influence of BESS score on BMI（B=4.12，P =0.027， 95% CI=0.48-7.75）and WC（B = 3.47，P = 0.046， 95% CI = 0.07 - 6.88）was significant. The influence of FRT distance on BMI（B = -5.68，P = 0.001， 95% CI = -8.95 - 2.41）and WC（B = -4.71，P = 0.003， 95% CI = -7.83 to -1.61）was significant， which indicated that the static and dynamic balance ability of obese people was worse with the increase of BMI， and the ability of dynamic and static balance of central obesity was worse than that of normal WC. ConclusionWaist circumference is an independent factor affecting the dynamic and static balance function of overweight and obese people. Under similar BMI， the dynamic balance function of central obese people is worse than that of people with normal waist circumference， leading to higher risk of falling.

Identification of TH Variants in Chinese Dopa-Responsive Dystonia Patients and Long-Term Outcomes.

Background: Dopa-responsive dystonia (DRD) is a movement disorder that is highly clinically and genetically heterogeneous. Our study summarizes clinical characteristics and long-term outcomes in patients with dopa-responsive dystonia with the aim of obtaining further knowledge on this disorder. Methods: Patients who met DRD genetic diagnostic criteria through whole-exome sequencing and took levodopa for over 3 years were included in our study. Detailed information was collected on these patients, including family history, age at onset, age and dosage at starting levodopa, current medication and dosage, levodopa duration, diurnal fluctuation, and other clinical features. The Burke-Fahn-Marsden Dystonia Rating Scale-Motor (BFMDRS-M) score was used to evaluate patients' dystonia and variation after levodopa. According to the long-term outcomes, patients were further graded as good (dystonia improved by more than 50% after levodopa, and no further motor symptoms appeared) and poor (dystonia improved by <50% after levodopa, or new motor symptoms appeared). Results: A total of 20 DRD patients were included (11 with GCH1 variants, 9 with TH variants). During long-term levodopa treatment, three patients with TH variants (3/20, 15%) developed motor symptoms, including body jerks and paroxysmal symptoms, and responded well to increasing levodopa doses. The patient with homozygous mutation c.1481C>T/p. Thr494Met harbored more serious symptoms and poor response to levodopa and showed decreased cardiac uptake in MIBG. Conclusions: Most DRD patients showed satisfactory treatment outcomes after long-term levodopa, whereas few patients with TH variants presented motor symptoms, which is considered to be related to dopamine insufficiency. For patients with motor symptoms after long-term levodopa, increasing the dose slowly might be helpful to relieve symptoms.

Effect of Decomposed Zuoguiwan Recipes in Improving BMD of Ovariectomized Rats by Regulating OPG/RANKL Pathway Mediated by β2AR / 中国实验方剂学杂志

Objective:To investigate the mechanism of decomposed Zuoguiwan（ZGW） recipes in treating ovariectomized osteoporosis rats. Method:Forty Sprague-Dawley female rats were equally and randomly divided into Sham-operated group, ovariectomized model group, positive group, and low and high-dose ZGW groups. After 12 weeks of administration by gavage, the bone mineral density (BMD) of rats' distal femur was measured by micro-CT, the morphology of bone tissue were observed by hematoxylin-eosin staining (HE), β-cross-linked c-telopeptide of type Ι collagen (β-CTX) and bone-specific alkaline phosphatase (BALP) in serum were detected by enzyme-linked immunosorbent assay (ELISA), and the mRNA and protein expressions of β2AR, OPG and RANKL were evaluated by Western blot analysis and real-time quantitative polymerase chain reaction （PCR）. Result:Compared with Sham-operated group, BMD of rats in ovariectomized model group was decreased (P<0.01), morphology of bone tissue was destroyed, serum BALP was reduced, while β-CTX was boosted (P<0.01)，mRNA and protein expressions of OPG in tibia were reduced, while RANKL were increased, and mRNA and protein expressions of β2AR in the hypothalamus were decreased (P<0.05, P<0.01). Compared with ovariectomized model group, BMDs of rats in low and high-dose ZGW groups were increased (P<0.01), morphology of bone tissue was repaired, serum BALP and mRNA and protein expressions of OPG in tibia were up-regulated (P<0.05, P<0.01), whereas serum β-CTX and mRNA and protein expressions of β2AR in the hypothalamus and RANKL in tibia were down-regulated (P<0.05, P<0.01). Conclusion:Yang-nourishing components in decomposed Zuoguiwan recipes can improve BMD of ovariectomized rats by regulating OPG/RANKL pathway mediated by β2AR. "Seeking Yin in Yang" is a crucial mechanism of Zuoguiwan in treating ovariectomized osteoporosis in rats.

Effect of Zuoguiwan in Improving BMD and Trabecular Bone Microarchitecture in Ovariectomy-induced Osteoporosis Rats by Regulating RANKL/OPG Pathway Mediated by β2AR / 中国实验方剂学杂志

Objective: To investigate the mechanism of Zuoguiwan in treating ovariectomy-induced osteoporosis rats by receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) signaling pathway mediated by β2-adrenergic receptor (β2AR). Method: Forty Sprague-Dawley female rats were randomly divided into Sham-operated group (Sham) and four ovariectomized (OVX) subgroups. Rats in Sham and OVX groups were treated with 17β-estradiol (50 μg·kg-1·d-1), and low and high-dose ZGW (2.3,4.6 g·kg-1 lyophilized powder) for 3 months, respectively. Enzyme-linked immunosorbent assay (ELISA) was used to measure the serum markers of bone turnover. Micro-CT was used to evaluate and measure trabecular bone microarchitecture and bone mineral density (BMD) of the right distal femur. Western blot analysis and Real-time PCR were used to measure mRNA and protein expressions of β2AR, OPG and RANKL. Result: After 12 weeks of treatment with Zuoguiwan, the level of serum β-cross-linked c-telopeptide of type Ι collagen (β-CTX) (PPPβ2AR in the hypothalamus (PPConclusion: The mechanism of Zuoguiwan in alleviating BMD and trabecular bone microarchitecture in ovariectomy-induced osteoporosis rats might be related to the regulation of RANKL/OPG Pathway mediated by β2AR.

Results of bacterial resistance surveillance in a Guangdong hospital during 2015-2017 / 中国感染与化疗杂志

Objective To investigate the susceptibility profile of clinical isolates in the First Affiliated Hospital of Guangzhou Medical University during 2015-2017. Methods Susceptibility test was carried out using Kirby-Bauer method or automated systems. Results were analyzed according to CLSI 2017 breakpoints. Results A total of 17 645 clinical isolates were isolated from January 2015 to December 2017, including 3 091(17.5％)gram positive and 14 554(82.5％)gram negative bacteria. Methicillinresistant S. aureus(MRSA)and coagulase-negative Staphylococcus(MRCNS)accounted for 50.7％ and 77.9％, respectively. No staphylococcal isolates were found resistant to vancomycin, teicoplanin or linezolid. E. faecalis strains showed much lower resistance rate to most drugs tested than E. faecium. Nine(0.8％)E. faecalis isolates were found resistant to vancomycin. A total of 227 strains of the non-meningitis S. pneumoniae were tested, 44.1％ of which were isolated from adults and 55.9％ from children. Most of the S. pneumoniae isolated from adults and children were susceptible to penicillin(88.0％ and 81.1％, respectively). E. coli showed the highest proportion in three years. ESBLs were produced in 53.3％ of E. coli and 28.5％ of Klebsiella spp. A total of 255 strains of carbapenem-resistant Enterobacteriaceae(3.7％), 665 strains of carbapenem-resistant Pseudomonas aeruginosa(26.2％)and 900 strains of carbapenem-resistant Acinetobacter baumannii(57.5％)were identified. The annual change of prevalence was insignificant. A total of 141 strains of extensively-drug resistant Pseudomonas aeruginosa(5.6％)and 458 strains of extensively-drug resistant A. baumannii(29.3％)were identified, showing decreasing prevalence from 2015 to 2017. Conclusions The bacterial resistance in this hospital is relatively stable in the past three years, but it is still necessary to strengthen hospital infection control and management, and maintain good practice in surveillance of bacterial resistance.

Targeted gene capture sequencing in diagnosis of dystonia patients.

BACKGROUND: Dystonia is a movement disorder with high clinical and genetic heterogeneity. Molecular diagnosis is important for an accurate diagnosis of dystonia. Targeted gene capture sequencing has been an effective method for screening multiple candidate genes simultaneously. This method, however, has been rarely reported to be used with dystonia patients. OBJECTIVES AND METHODS: To assess the effectiveness of the targeted gene capture sequencing in dystonia, we performed custom target gene capture followed by next-generation sequencing in dystonia patients from China. Sanger sequencing was utilized to substantiate the findings. The effects of identified variants were classified according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines. RESULTS: A total of 65 patients (34 female and 31 male) were recruited in this study. The mean age at onset was 22.7 ±â€¯13.3 years ranging from 2 to 59 years. According to ACMG standards and guidelines, of 65 patients, 12 were identified with pathogenic variants (12/65, 18.5%) in gene TOR1A, PANK2 or ATP1A3, and another four were identified with likely-pathogenic variants (4/65, 6.2%) in gene PRRT2, GCH1 or THAP1. In total, 24.6% of patients in this cohort were detected to have a genetic cause of dystonia. Another four patients (4/65, 6.2%) were identified with variants which were considered to be VUS (Variants of Uncertain Significance) in gene SGCE, TH, ANO3 and ATP1A3 respectively. The most common detected gene was TOR1A, known to be causative for DYT1 (8/65, 12.3%). CONCLUSIONS: The study demonstrates that targeted gene capture sequencing is an effective tool for identifying the genetic cause of heterogeneous dystonia patients.

Policy and political advocacy: Comparison study of nursing faculty to determine current practices, perceptions, and barriers to teaching health policy.

PURPOSE: To better understand policy/advocacy concepts and methodology utilized in all levels of nursing educational programs and develop clarity concerning structure of policy content and integration across all levels of education. DESIGN AND METHODS: Cross-sectional analysis of data obtained from a survey sent to 19,043 nursing faculty in the United States; 598 total responses; 514 complete responses. Quantitative data points were analyzed using SPSS and qualitative data was grouped and analyzed by theme. FINDINGS: Barriers and perceptions of student engagement and student learning outcomes along with institutional and faculty development barriers were explored in baccalaureate, masters, and doctoral level nursing programs. Thirty-six percent of respondents reported having experience in development and implementation of policy, ranging from local to international spheres and 21% reported active involvement in current state and federal policy development. Seventy percent of respondents have advocated for the nursing profession through professional organizations while 44% report current activity in legislative advocacy. CONCLUSIONS: The value of nursing policy education, advocacy, and analysis must be valued in higher education.

A model of tailoring effects: A randomized controlled trial examining the mechanisms of tailoring in a web-based STD screening intervention.

OBJECTIVE: This study explores the mechanisms of tailoring within the context of RU@Risk a brief Web-based intervention designed to promote sexually transmitted disease (STD) testing among young adults. This is one of a few studies to empirically examine theorized message processing mechanisms of tailoring and persuasion outcomes in a single model. METHOD: Sexually active college students (N = 1065) completed a pretest, were randomly assigned to explore a tailored or nontailored website, completed a posttest, and were offered the opportunity to order a free at-home STD test kit. As intervention effects were hypothesized to work via increases in perceived risk, change in perceived risk from pretest to posttest by condition was examined. Hypothesized mechanisms of tailoring (perceived personal relevance, attention, and elaboration) were examined using structural equation modeling (SEM). All analyses controlled for demographic variables and sexual history. RESULTS: As predicted, perceived risk of STDs increased from pretest to posttest, but only in the tailored condition. Results revealed that exposure to the tailored (vs. nontailored) website increased perceived personal relevance, attention to, and elaboration of the message. These effects in turn were associated with greater perceived risk of STDs and intentions to get tested. Additionally, participants in the tailored condition were more likely to order a test kit. CONCLUSIONS: Findings provide insight into the mechanisms of tailoring with important implications for optimizing message design. (PsycINFO Database Record

Political advocacy and practice barriers: a survey of Florida APRNs.

PURPOSE: This study examined factors aligned with advocacy among advanced practice registered nurses (APRNs) by examining the relationships among demographics, years of RN and APRN experience, education levels, affiliations with professional organizations, perceptions of barriers to practice, political activism, and willingness to speak to the media. DATA SOURCES: This was a secondary analysis of online survey data (N = 884) from APRNs in Florida. All APRNs with an e-mail address with the state nursing board or a Florida Coalition of Advanced Practice Nurses' membership organization received an e-mail requesting their participation to the survey. CONCLUSIONS: Having a high educational level and involvement in a professional organization are each individually statistically associated with perceiving practice barriers, engaging in political activism, and willingness to speak with media. Emerging nurse leaders need an understanding of policy issues, an appreciation of the potential of the profession, and enhanced advocacy skills. IMPLICATIONS FOR PRACTICE: To address the nation's health needs, APRNs need to recognize practice barriers, develop advocacy skills, and take action for policy changes to enhance the legal authority to practice to full extent of APRNs' education and training.

Characteristics of nurses who use social media.

Social media are changing the ways people communicate and influencing their approaches to meeting their healthcare needs. The Institute of Medicine recommends utilization of information technologies to improve the delivery of patient-centered care. Little is known about how nurses have adopted the use of social media, however. The researchers conducted an online survey to provide a preliminary review of the characteristics of nurses who do and do not use social media. Also, nurses' preferences for using six different types of social media were analyzed and reported. Nurses from 43 states participated in this study, and the sample represented mostly advanced practice nurses who utilized the Internet regularly and confidently. About 94% of the participants indicated that they use social media, whereas fewer than 1% of the participants reported that they do not know how to use social media. Among those who use social media, social networking sites (90.33%) and podcasts (76.24%) were the most popular, followed by social question and asking sites (37.86%), blogs (31.85%), Twitter (19.06%), and SlideShare (9.92%). Social media can be a powerful tool to reach an intended audience quickly and globally. More research is needed to understand how nurses utilize social media to improve the delivery of patient-centered care.

A quality improvement project to increase influenza vaccination in healthcare personnel at a university health center.

PURPOSE: The purpose of this quality improvement project was to increase the healthcare personnel (HCP) influenza vaccine uptake at a university student health center. DATA SOURCES: A descriptive design was used. A preintervention survey identified facilitators and barriers to HCP's uptake of influenza vaccine. Based on the results of this survey, four interventions were implemented. The postintervention survey was administered to assess for intervention effectiveness. CONCLUSIONS: The most common facilitators for influenza vaccination uptake on the preintervention survey were as follows: (a) protect self/family, (b) free vaccine, (c) recommended by experts, and (d) convenient vaccination process. The most common barrier was concern about vaccine side effects. Postintervention, the vaccination uptake increased from 71% in 2008-2009 to 77% in 2009-2010. Free vaccine and convenient vaccination process were rated as the most effective interventions. Education and the declination form used for the project were rated less favorably. IMPLICATIONS FOR PRACTICE: Factors influencing vaccine uptake may be different across practice settings. It is important to identify facilitators and barriers that are unique to health centers to better plan and implement interventions to improve vaccination rates. Furthermore, at a time when resources are limited, it is critical to identify the most effective strategies to maximize outcomes.

Research advances in corneal newborn lymphatic vessel and corneal transplantation rejection / 国际眼科杂志(Guoji Yanke Zazhi)

Corneal newborn lymphatic vessels construct the afferent arc of corneal immunological reaction, which play important role in immune response. The corneal transplantation rejection rate rises due to the emergence of new lymphatic vessel which breaks the immunologic mechanism. With the founding of specific marker of lymphatic endothelial cells and research advancing of growth factor of lymphatic vessels, the mechanism, therapy and prevention of corneal immunological rejection reaction of corneal lymphatic vessel have been studied intensively. The graft survival rate has been greatly improved through inhibiting newborn lymphatic vessel.

Subcellular distribution of THAP1 and alterations in the microstructure of brain white matter in DYT6 dystonia.

BACKGROUND: Mutations in the THAP1 gene have recently been identified as the cause of DYT6 primary dystonia. However, the changes in THAP1 gene function and in the microstructure of brain white matter have not been well-characterized. METHODS: Four different mutations of THAP1 expression (clones F22fs71X, C54F, F25fs53X, and L180S) were transfected into HEK-293T cells. The subcellular distribution of THAP1 in each clone was identified using immunofluorescence microscopy and Western blot. Six patients who harbored these THAP1 mutations underwent diffusion tensor magnetic resonance imaging (DTI) of the brain. The fractional anisotropy (FA) and mean diffusivity (MD) were measured in twenty-four regions of interest (ROI). RESULTS: In two truncated mutations (F22fs71X and F25fs53X), the subcellular distribution of THAP1 were both in the cytoplasm and nucleus. However, the subcellular distribution was detected almost in the nucleus in two missense mutations (C54F and L180S). In the DTI maps, the average values of fractional anisotropy (FA), a measure of axonal integrity and coherence, was reduced (p < 0.005) in the subgyral white matter of the sensorimotor cortex of the DYT1 carriers, comparing with controls. CONCLUSIONS: Truncated THAP1 mutations (F22fs71X and F25fs53X) can alter the subcellular distributions, while some missense mutation (C54F and L180S) can not. The axonal integrity and coherence in the region of sensorimotor area of the brain was damaged in DYT6 dystonia.

THAP1/DYT6 sequence variants in non-DYT1 early-onset primary dystonia in China and their effects on RNA expression.

Mutations in the THAP1 gene were recently identified as the cause of DYT6 primary dystonia. More than 40 mutations in this gene have been described in different populations. However, no previous report has identified sequence variations that affect the transcript process of the THAP1 gene. In addition, the mutation frequency in Chinese early-onset primary dystonia has not been well characterized. One hundred and two unrelated patients with non-DYT1 early-onset primary dystonia (age at onset <26 years), family members of participants with mutations, and 200 neurologically normal controls were screened for THAP1 gene mutations. The effects of the identified mutations on RNA expression were analyzed using semi-quantitative real-time PCR. Seven sequence variants (c.63_66del TTTC, c.161G>T, c.224A>T, c.267G>A, c.339T>C, c.449A>C, and c.539T>C) were identified in this group of patients (6.9%). In this cohort, 15 subjects (seven unrelated patients and eight family members) were detected to have THAP1 sequence variants. Among these 15 subjects, 11 were manifested (penetrance of DYT6 was 73.3%) and seven presented with craniocervical involvement (63.6%). However, one patient manifested paroxysmal headshake, and one presented with essential hand tremor. Semi-quantitative real-time PCR indicated that a novel silent mutation (c.267G>A) decreased the expression of THAP1 in human lymphocytes. Our findings indicated that THAP1 sequence variants are not common in non-DYT1 early-onset primary dystonia in China and that the clinical manifestation may vary. One silent mutation (c.267G>A) was shown to affect THAP1 expression.