2,652 research outputs found

    Analyzing Gene Expression Profile in K562 Cells Exposed to Sodium Valproate Using Microarray Combined with the Connectivity Map Database

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    To explore the mechanism underlying antileukaemia effect of sodium valproate, the growth and survival of the K562 cell line were investigated. Global profiles of gene expression in K562 cells exposed to sodium valproate were assessed and validated. The differentially expressed genes identified were further used to query the connectivity map database to retrieve a ranked list of compounds that act on the same intracellular targets as sodium valproate. A significant increase in cell apoptosis and a change in gene expression profile were observed in valproate-exposed K562 cells. The significant enrichment analysis of gene ontology terms for the differentially expressed genes showed that these genes were involved in many important biological processes. Eight differentially expressed genes involved in apoptosis were verified by quantitative real-time PCR. The connectivity map analysis showed gene expression profile in K562 cells exposed to sodium valproate was most similar to that of HDACi and PI3K inhibitors, suggesting that sodium valproate might exert antileukaemic action by inhibiting HDAC as well as inhibiting PI3K pathway. In conclusion, our data might provide clues to elucidate the molecular and therapeutic potential of VPA in leukaemia treatment, and the connectivity map is a useful tool for exploring the molecular mechanism of drug action

    Nonparametric and semi-parametric panel data models: recent developments

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    ABSTRACT: In this paper, we provide an intensive review of the recent developments for semiparametric and fully nonparametric panel data models that are linearly separable in the innovation and the individual-specific term. We analyze these developments under two alternative model specifications: fixed and random effects panel data models. More precisely, in the random effects setting, we focus our attention in the analysis of some efficiency issues that have to do with the so-called working independence condition. This assumption is introduced when estimating the asymptotic variance-covariance matrix of nonparametric estimators. In the fixed effects setting, to cope with the so-called incidental parameters problem, we consider two different estimation approaches: profiling techniques and differencing methods. Furthermore, we are also interested in the endogeneity problem and how instrumental variables are used in this context. In Addition, for practitioners, we also show different ways of avoiding the so-called curse of dimensionality problem in pure nonparametric models. In this way, semiparametric and additive models appear as a solution when the number of explanatory variables is large

    The role of quality of care and attitude towards disability in the relationship between severity of disability and quality of life: findings from a cross-sectional survey among people with physical disability in China

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    Background: People with physical disability (PWPD) is the largest subgroup of people with disability (PWD) in China, but few studies have been conducted among this vulnerable population. The objective of this study was to investigate the level of quality of life (QoL), self-perceived quality of care and support (QOCS), severity of disability and personal attitude towards disability among people with physical disability in China, as well as to identify how QoL can be affected by severity of disability through QOCS and personal attitude towards disability among PWPD. Methods: A cross-sectional study was conducted among 1,853 PWPD in Guangzhou, China. Data were collected on participants’ QoL, QOCS, personal attitude towards disability and severity of disability. Structural equation modeling was used to examine the effects of the other variables on QoL. Results: Even with a mild disability (mean score:1.72), relatively low levels of QoL (mean score: 2.65- 3.22) and QOCS (mean score: 2.95 to 3.28), as well as unfavorable personal attitude towards disability (mean score: 2.75 to 3.36) were identified among PWPD. According to SEM, we found that the influence of severity of physical disability on QoL is not only exerted directly, but is also indirectly through QOCS and their personal attitudes towards disability, with QOCS playing a more important mediating role than PWPD’s attitudes towards their own disability. Conclusions: Unfavorable health status was identified among PWPD in China. Focusing on improvement of assistance and care services has the potential to substantially improve PWPD’s QoL. Further research should focus on understanding the needs and their current state of health care of PWPD in China thus being able to develop better interventions for them

    The controlling nutritional status score predicts postoperative mortality in patients with ruptured abdominal aortic aneurysm: a retrospective study

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    BackgroundRuptured abdominal aortic aneurysms (rAAAs) are challenging for vascular surgeons because they have a high mortality rate. In many diseases, nutritional status is closely associated with prognosis. The Controlling Nutritional Status (CONUT) screening tool score is a prognostic factor in some malignant and chronic diseases; however, the impact of nutritional status on rAAA has not yet been reported. In this study, we explored the relationship between the CONUT score and the postoperative prognosis of patients with rAAA.MethodsThis was a retrospective review of 39 patients with rAAA who underwent surgical treatment from March 2018 to September 2021 at one center. Patient characteristics, nutritional status (CONUT score), and postoperative status were recorded. The patients were divided into groups A and B based on the CONUT score. The baseline characteristics of the two groups were compared, and Cox proportional hazards and logistic regression analyses were used to determine independent predictors of mid-term mortality and complications, respectively.ResultsThe overall mid-term mortality rate was 28.21% (11/39). Compared with group A, group B had higher intraoperative (P = 0.047) and mid-term mortality (P = 0.033) rates. The univariate analysis showed that age [hazard ratio (HR), 1.098; 95% confidence interval (CI), 1.019–1.182; P = 0.014], CONUT score (HR, 1.316; 95% CI, 1.027–1.686; P = 0.03), and surgical procedure (HR, 0.127; 95% CI, 0.016–0.992; P = 0.049) were associated with mid-term mortality, whereas the multivariate analysis showed that the CONUT score (HR, 1.313; 95% CI, 1.009–1.710; P = 0.043) was an independent predictor of mid-term mortality. The multivariate logistic regression analysis did not reveal any associations with complications. The Kaplan–Meier curves showed that group B had a lower mid-term survival rate (log-rank P = 0.024).ConclusionMalnutrition is closely associated with the prognosis of patients with rAAA, and the CONUT score can be used to predict mid-term mortality

    Knowledge and attitudes of healthcare workers in Chinese intensive care units regarding 2009 H1N1 influenza pandemic

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    <p>Abstract</p> <p>Background</p> <p>To describe the knowledge and attitudes of critical care clinicians during the 2009 H1N1 influenza pandemic.</p> <p>Methods</p> <p>A survey conducted in 21 intensive care units in 17 provinces in China.</p> <p>Results</p> <p>Out of 733 questionnaires distributed, 695 were completed. Three hundred and fifty-six respondents (51.2%) reported their experience of caring for H1N1 patients. Despite the fact that 88.5% of all respondents ultimately finished an H1N1 training program, only 41.9% admitted that they had the knowledge of 2009 H1N1 influenza. A total of 572 respondents (82.3%) expressed willingness to care for H1N1 patients. Independent variables associated with increasing likelihood to care for patients in the logistic regression analysis were physicians or nurses rather than other professionals (odds ratio 4.056 and 3.235, p = 0.002 and 0.007, respectively), knowledge training prior to patient care (odds ratio 1.531, p = 0.044), and the confidence to know how to protect themselves and their patients (odds ratio 2.109, p = 0.001).</p> <p>Conclusion</p> <p>Critical care clinicians reported poor knowledge of H1N1 influenza, even though most finished a relevant knowledge training program. Implementation of appropriate education program might improve compliance to infection control measures, and willingness to work in a pandemic.</p

    Silymarin Targets β-Catenin Signaling in Blocking Migration/Invasion of Human Melanoma Cells

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    Metastatic melanoma is a leading cause of death from skin diseases, and is often associated with activation of Wnt/β-catenin signaling pathway. We have examined the inhibitory effect of silymarin, a plant flavanoid from Silybum marianum, on cell migration of metastasis-specific human melanoma cell lines (A375 and Hs294t) and assessed whether Wnt/β-catenin signaling is the target of silymarin. Using an in vitro invasion assay, we found that treatment of human melanoma cell lines with silymarin resulted in concentration-dependent inhibition of cell migration, which was associated with accumulation of cytosolic β-catenin, while reducing the nuclear accumulation of β-catenin (i.e., β-catenin inactivation) and reducing the levels of matrix metalloproteinase (MMP) -2 and MMP-9 which are the down-stream targets of β-catenin. Silymarin enhanced: (i) the levels of casein kinase 1α, glycogen synthase kinase-3β and phosphorylated-β-catenin on critical residues Ser45, Ser33/37 and Thr41, and (ii) the binding of β-transducin repeat-containing proteins (β-TrCP) with phospho forms of β-catenin in melanoma cells. These events play important roles in degradation or inactivation of β-catenin. To verify whether β-catenin is a potent molecular target of silymarin, the effect of silymarin was determined on β-catenin-activated (Mel 1241) and β-catenin-inactivated (Mel 1011) melanoma cells. Treatment of Mel 1241 cells with silymarin or FH535, an inhibitor of Wnt/β-catenin pathway, significantly inhibited cell migration of Mel 1241 cells, which was associated with the elevated levels of casein kinase 1α and glycogen synthase kinase-3β, and decreased accumulation of nuclear β-catenin and inhibition of MMP-2 and MMP-9 levels. However, this effect of silymarin and FH535 was not found in Mel 1011 melanoma cells. These results indicate for the first time that silymarin inhibits melanoma cell migration by targeting β-catenin signaling pathway

    The Effects of Puerarin on Rat Ventricular Myocytes and the Potential Mechanism

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    Puerarin, a known isoflavone, is commonly found as a Chinese herb medicine. It is widely used in China to treat cardiac diseases such as angina, cardiac infarction and arrhythmia. However, its cardioprotective mechanism remains unclear. In this study, puerarin significantly prolonged ventricular action potential duration (APD) with a dosage dependent manner in the micromolar range on isolated rat ventricular myocytes. However, submicromolar puerarin had no effect on resting membrane potential (RMP), action potential amplitude (APA) and maximal velocity of depolarization (Vmax) of action potential. Only above the concentration of 10 mM, puerarin exhibited more aggressive effect on action potential, and shifted RMP to the positive direction. Millimolar concentrations of puerarin significantly inhibited inward rectified K+ channels in a dosage dependent manner, and exhibited bigger effects upon Kir2.1 vs Kir2.3 in transfected HEK293 cells. As low as micromolar range concentrations of puerarin significantly inhibited Kv7.1 and IKs. These inhibitory effects may due to the direct inhibition of puerarin upon channels not via the PKA-dependent pathway. These results provided direct preclinical evidence that puerarin prolonged APD via its inhibitory effect upon Kv7.1 and IKs, contributing to a better understanding the mechanism of puerarin cardioprotection in the treatment of cardiovascular diseases

    Peer-based behavioral health program for drug users in China: a pilot study

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    <p>Abstract</p> <p>Background</p> <p>Many injection drug users (IDUs) in China have high risk sexual behaviors that contribute to the spread of HIV infection. Although many IDUs in China move through drug rehabilitation centers, this opportunity for sexual health education has largely been overlooked.</p> <p>Methods</p> <p>A convenience sample of 667 drug users from two rehabilitation centers in South China was recruited in the study. Two hundred and forty seven drug users from a single Guangdong Province rehabilitation center received the peer-based education intervention, while 420 drug users from another rehabilitation center received routine HIV/STI education and was used as the control. One hundred and eighty nine (22.1%) individuals refused to participate in the study. HIV/STI behavioral and knowledge domains were assessed at 3 months in rehabilitation centers after the intervention (first follow-up) and at 2-23 months in the community after release (second follow-up).</p> <p>Results</p> <p>Drug users who completed the intervention reported more frequent condom use with casual sex partners (60.0% vs. 12.5% condom use every time, p = 0.011) and less frequent injection (56.7% vs. 26.4% no injection per day, p = 0.008) at the second follow-up compared to those in the routine education group. Loss to follow up was substantial in both control and intervention groups, and was associated with living far from the detention center and having poor HIV knowledge at baseline.</p> <p>Conclusions</p> <p>This study shows that rehabilitation centers may be a useful location for providing behavioral HIV/STI prevention services and referral of individuals to community-based programs upon release. More research is needed on behalf of detained drug users in China who have complex social, medical, and legal needs.</p

    Peer-based behavioral health program for drug users in China: a pilot study

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    <p>Abstract</p> <p>Background</p> <p>Many injection drug users (IDUs) in China have high risk sexual behaviors that contribute to the spread of HIV infection. Although many IDUs in China move through drug rehabilitation centers, this opportunity for sexual health education has largely been overlooked.</p> <p>Methods</p> <p>A convenience sample of 667 drug users from two rehabilitation centers in South China was recruited in the study. Two hundred and forty seven drug users from a single Guangdong Province rehabilitation center received the peer-based education intervention, while 420 drug users from another rehabilitation center received routine HIV/STI education and was used as the control. One hundred and eighty nine (22.1%) individuals refused to participate in the study. HIV/STI behavioral and knowledge domains were assessed at 3 months in rehabilitation centers after the intervention (first follow-up) and at 2-23 months in the community after release (second follow-up).</p> <p>Results</p> <p>Drug users who completed the intervention reported more frequent condom use with casual sex partners (60.0% vs. 12.5% condom use every time, p = 0.011) and less frequent injection (56.7% vs. 26.4% no injection per day, p = 0.008) at the second follow-up compared to those in the routine education group. Loss to follow up was substantial in both control and intervention groups, and was associated with living far from the detention center and having poor HIV knowledge at baseline.</p> <p>Conclusions</p> <p>This study shows that rehabilitation centers may be a useful location for providing behavioral HIV/STI prevention services and referral of individuals to community-based programs upon release. More research is needed on behalf of detained drug users in China who have complex social, medical, and legal needs.</p

    Towards a global One Health index: a potential assessment tool for One Health performance

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    BACKGROUND: A One Health approach has been increasingly mainstreamed by the international community, as it provides for holistic thinking in recognizing the close links and inter-dependence of the health of humans, animals and the environment. However, the dearth of real-world evidence has hampered application of a One Health approach in shaping policies and practice. This study proposes the development of a potential evaluation tool for One Health performance, in order to contribute to the scientific measurement of One Health approach and the identification of gaps where One Health capacity building is most urgently needed. METHODS: We describe five steps towards a global One Health index (GOHI), including (i) framework formulation; (ii) indicator selection; (iii) database building; (iv) weight determination; and (v) GOHI scores calculation. A cell-like framework for GOHI is proposed, which comprises an external drivers index (EDI), an intrinsic drivers index (IDI) and a core drivers index (CDI). We construct the indicator scheme for GOHI based on this framework after multiple rounds of panel discussions with our expert advisory committee. A fuzzy analytical hierarchy process is adopted to determine the weights for each of the indicators. RESULTS: The weighted indicator scheme of GOHI comprises three first-level indicators, 13 second-level indicators, and 57 third-level indicators. According to the pilot analysis based on the data from more than 200 countries/territories the GOHI scores overall are far from ideal (the highest score of 65.0 out of a maximum score of 100), and we found considerable variations among different countries/territories (31.8–65.0). The results from the pilot analysis are consistent with the results from a literature review, which suggests that a GOHI as a potential tool for the assessment of One Health performance might be feasible. CONCLUSIONS: GOHI—subject to rigorous validation—would represent the world’s first evaluation tool that constructs the conceptual framework from a holistic perspective of One Health. Future application of GOHI might promote a common understanding of a strong One Health approach and provide reference for promoting effective measures to strengthen One Health capacity building. With further adaptations under various scenarios, GOHI, along with its technical protocols and databases, will be updated regularly to address current technical limitations, and capture new knowledge. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40249-022-00979-9
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