LAMTOR1 inhibition of TRPML1-dependent lysosomal calcium release regulates dendritic lysosome trafficking and hippocampal neuronal function.

Lysosomes function not only as degradatory compartments but also as dynamic intracellular calcium ion stores. The transient receptor potential mucolipin 1 (TRPML1) channel mediates lysosomal Ca2+ release, thereby participating in multiple cellular functions. The pentameric Ragulator complex, which plays a critical role in the activation of mTORC1, is also involved in lysosomal trafficking and is anchored to lysosomes through its LAMTOR1 subunit. Here, we report that the Ragulator restricts lysosomal trafficking in dendrites of hippocampal neurons via LAMTOR1-mediated tonic inhibition of TRPML1 activity, independently of mTORC1. LAMTOR1 directly interacts with TRPML1 through its N-terminal domain. Eliminating this inhibition in hippocampal neurons by LAMTOR1 deletion or by disrupting LAMTOR1-TRPML1 binding increases TRPML1-mediated Ca2+ release and facilitates dendritic lysosomal trafficking powered by dynein. LAMTOR1 deletion in the hippocampal CA1 region of adult mice results in alterations in synaptic plasticity, and in impaired object-recognition memory and contextual fear conditioning, due to TRPML1 activation. Mechanistically, changes in synaptic plasticity are associated with increased GluA1 dephosphorylation by calcineurin and lysosomal degradation. Thus, LAMTOR1-mediated inhibition of TRPML1 is critical for regulating dendritic lysosomal motility, synaptic plasticity, and learning.

Identification and Analysis of the Mechanism of Stem Mechanical Strength Enhancement for Maize Inbred Lines QY1.

Enhancing stalk strength is a crucial strategy to reduce lodging. We identified a maize inbred line, QY1, with superior stalk mechanical strength. Comprehensive analyses of the microstructure, cell wall composition, and transcriptome of QY1 were performed to elucidate the underlying factors contributing to its increased strength. Notably, both the vascular bundle area and the thickness of the sclerenchyma cell walls in QY1 were significantly increased. Furthermore, analyses of cell wall components revealed a significant increase in cellulose content and a notable reduction in lignin content. RNA sequencing (RNA-seq) revealed changes in the expression of numerous genes involved in cell wall synthesis and modification, especially those encoding pectin methylesterase (PME). Variations in PME activity and the degree of methylesterification were noted. Additionally, glycolytic efficiency in QY1 was significantly enhanced. These findings indicate that QY1 could be a valuable resource for the development of maize varieties with enhanced stalk mechanical strength and for biofuel production.

Fine-tuning brassinosteroid biosynthesis via 3'UTR-dependent decay of CPD mRNA modulates wood formation in Populus.

Brassinosteroids (BRs) are plant hormones that regulate wood formation in trees. Currently, little is known about the post-transcriptional regulation of BR synthesis. Here, we show that during wood formation, fine-tuning BR synthesis requires 3'UTR-dependent decay of Populus CONSTITUTIVE PHOTOMORPHOGENIC DWARF 1 (PdCPD1). Overexpression of PdCPD1 or its 3' UTR fragment resulted in a significant increase of BR levels and inhibited secondary growth. In contrast, transgenic poplars repressing PdCPD1 3' UTR expression displayed moderate levels of BR and promoted wood formation. We show that the Populus GLYCINE-RICH RNA-BINDING PROTEIN 1 (PdGRP1) directly binds to a GU-rich element in 3' UTR of PdCPD1, leading to its mRNA decay. We thus provide a post-transcriptional mechanism underlying BRs synthesis during wood formation, which may be useful for genetic manipulation of wood biomass in trees.

Lack of UBE3A-Mediated Regulation of Synaptic SK2 Channels Contributes to Learning and Memory Impairment in the Female Mouse Model of Angelman Syndrome.

Angelman syndrome (AS) is a rare neurodevelopmental disorder characterized by severe developmental delay, motor impairment, language and cognition deficits, and often with increased seizure activity. AS is caused by deficiency of UBE3A, which is both an E3 ligase and a cofactor for transcriptional regulation. We previously showed that the small conductance potassium channel protein SK2 is a UBE3A substrate, and that increased synaptic SK2 levels contribute to impairments in synaptic plasticity and fear-conditioning memory, as inhibition of SK2 channels significantly improved both synaptic plasticity and fear memory in male AS mice. In the present study, we investigated UBE3a-mediated regulation of synaptic plasticity and fear-conditioning in female AS mice. Results from both western blot and immunofluorescence analyses showed that synaptic SK2 levels were significantly increased in hippocampus of female AS mice, as compared to wild-type (WT) littermates. Like in male AS mice, long-term potentiation (LTP) was significantly reduced while long-term depression (LTD) was enhanced at hippocampal CA3-CA1 synapses of female AS mice, as compared to female WT mice. Both alterations were significantly reduced by treatment with the SK2 inhibitor, apamin. The shunting effect of SK2 channels on NMDA receptor was significantly larger in female AS mice as compared to female WT mice. Female AS mice also showed impairment in both contextual and tone memory recall, and this impairment was significantly reduced by apamin treatment. Our results indicate that like male AS mice, female AS mice showed significant impairment in both synaptic plasticity and fear-conditioning memory due to increased levels of synaptic SK2 channels. Any therapeutic strategy to reduce SK2-mediated inhibition of NMDAR should be beneficial to both male and female patients.

Gendered health systems: evidence from low- and middle-income countries.

BACKGROUND: Gender is often neglected in health systems, yet health systems are not gender neutral. Within health systems research, gender analysis seeks to understand how gender power relations create inequities in access to resources, the distribution of labour and roles, social norms and values, and decision-making. This paper synthesises findings from nine studies focusing on four health systems domains, namely human resources, service delivery, governance and financing. It provides examples of how a gendered and/or intersectional gender approach can be applied by researchers in a range of low- and middle-income settings (Cambodia, Zimbabwe, Uganda, India, China, Nigeria and Tanzania) to issues across the health system and demonstrates that these types of analysis can uncover new and novel ways of viewing seemingly intractable problems. METHODS: The research used a combination of mixed, quantitative, qualitative and participatory methods, demonstrating the applicability of diverse research methods for gender and intersectional analysis. Within each study, the researchers adapted and applied a variety of gender and intersectional tools to assist with data collection and analysis, including different gender frameworks. Some researchers used participatory tools, such as photovoice and life histories, to prompt deeper and more personal reflections on gender norms from respondents, whereas others used conventional qualitative methods (in-depth interviews, focus group discussion). Findings from across the studies were reviewed and key themes were extracted and summarised. RESULTS: Five core themes that cut across the different projects were identified and are reported in this paper as follows: the intersection of gender with other social stratifiers; the importance of male involvement; the influence of gendered social norms on health system structures and processes; reliance on (often female) unpaid carers within the health system; and the role of gender within policy and practice. These themes indicate the relevance of and need for gender analysis within health systems research. CONCLUSION: The implications of the diverse examples of gender and health systems research highlighted indicate that policy-makers, health practitioners and others interested in enhancing health system research and delivery have solid grounds to advance their enquiry and that one-size-fits-all heath interventions that ignore gender and intersectionality dimensions require caution. It is essential that we build upon these insights in our efforts and commitment to move towards greater equity both locally and globally.

Identifying community healthcare supports for the elderly and the factors affecting their aging care model preference: evidence from three districts of Beijing.

BACKGROUND: The Chinese tradition of filial piety, which prioritized family-based care for the elderly, is transitioning and elders can no longer necessarily rely on their children. The purpose of this study was to identify community support for the elderly, and analyze the factors that affect which model of old-age care elderly people dwelling in communities prefer. METHODS: We used the database "Health and Social Support of Elderly Population in Community". Questionnaires were issued in 2013, covering 3 districts in Beijing. A group of 1036 people over 60 years in age were included in the study. The respondents' profile variables were organized in Andersen's Model and community healthcare resource factors were added. A multinomial logistic model was applied to analyze the factors associated with the desired aging care models. RESULTS: Cohabiting with children and relying on care from family was still the primary desired aging care model for seniors (78 %), followed by living in institutions (14.8 %) and living at home independently while relying on community resources (7.2 %). The regression result indicated that predisposing, enabling and community factors were significantly associated with the aging care model preference. Specifically, compared with those who preferred to cohabit with children, those having higher education, fewer available family and friend helpers, and shorter distance to healthcare center were more likely to prefer to live independently and rely on community support. And compared with choosing to live in institutions, those having fewer available family and friend helpers and those living alone were more likely to prefer to live independently and rely on community. Need factors (health and disability condition) were not significantly associated with desired aging care models, indicating that desired aging care models were passive choices resulted from the balancing of family and social caring resources. CONCLUSIONS: In Beijing, China, aging care arrangement preference is the result of balancing family care resources, economic and social status, and the accessibility of community resources. Community facilities and services supporting elderly were found to be insufficient. For China's future health system, efforts should be made to improve community capacity to provide integrated services to senior citizens.

Contextual fear memory impairment in Angelman syndrome model mice is associated with altered transcriptional responses.

Angelman syndrome (AS) is a rare neurogenetic disorder caused by UBE3A deficiency and characterized by severe developmental delay, cognitive impairment, and motor dysfunction. In the present study, we performed RNA-seq on hippocampal samples from both wildtype (WT) and AS male mice, with or without contextual fear memory recall. There were 281 recall-associated differentially expressed genes (DEGs) in WT mice and 268 DEGs in AS mice, with 129 shared by the two genotypes. Gene ontology analysis showed that extracellular matrix and stimulation-induced response genes were prominently enriched in recall-associated DEGs in WT mice, while nuclear acid metabolism and tissue development genes were highly enriched in those from AS mice. Further analyses showed that the 129 shared DEGs belonged to nuclear acid metabolism and tissue development genes. Unique recall DEGs in WT mice were enriched in biological processes critical for synaptic plasticity and learning and memory, including the extracellular matrix network clustered around fibronectin 1 and collagens. In contrast, AS-specific DEGs were not enriched in any known pathways. These results suggest that memory recall in AS mice, while altering the transcriptome, fails to recruit memory-associated transcriptional programs, which could be responsible for the memory impairment in AS mice.

The association between falls and depressive symptoms among older adults: evidence from the China Health and Retirement Longitudinal Study.

Background: Falls place a heavy burden on older adults and families, and there was little research on the relationship between falls and depressive symptoms among older adults in China. This study is designed to examine the association between falls and depressive symptoms in Chinese older adults. Methods: This study was based on 9,539 data sets from the China Health and Retirement Longitudinal Study (CHARLS) in 2018. The 10-item Center for Epidemiologic Studies-Depression Scale (CESD-10) was used to access depressive symptoms in older adults. A logistic regression model was used to calculate multivariate odds ratios (ORs) and 95% confidence intervals (CIs) for falls and depressive symptoms, adjusted for possible confounders. The Classification and regression tree (CART) demonstrates the prediction of the target variable values based on other variables. Results: In this study, 9,539 older people were selected: 60-69 years old accounted for 63.0%, 70-79 years old accounted for 29.7%, and 80 years old and above accounted for 7.3%. Male accounted for 49.7% and female for 50.3%. The rate of falls among older adults was 21.4%, and the rate of depressive symptoms was 33.9%. Adjusted ORs (OR = 1.37, 95% CI: 1.23, 1.53) showed a significant association between falls and depressive symptoms among older adults. Subgroup analysis revealed that this association was statistically significant across male (OR = 1.29, 95% CI: 1.23, 1.53) and female (OR = 1.42, 95% CI: 1.23, 1.64), 60-69 aged (OR = 1.38, 95% CI: 1.19, 1.60) and 70-79 aged (OR =1.42, 95% CI: 1.16, 1.74), rural (OR = 1.42, 95% CI: 1.25, 1.61), <15,000 CNY (OR = 1.35, 95% CI: 1.19, 1.54) and more than 25,000 CNY (OR = 1.42, 95% CI: 1.09, 1.85). Additionally, The CART model showed that the probability (73.0%) of falls was highest among older adults with depressive symptoms who self-rated poor health and female gender. Conclusions: This cross-sectional study demonstrated a significant association between falls and depressive symptoms in Chinese older adults. The findings provide some evidence and support for risk monitoring, screening for depressive symptoms, and early prevention in the high-risk older population.

UBE3A deficiency-induced autophagy is associated with activation of AMPK-ULK1 and p53 pathways.

Angelman Syndrome (AS) is a neurodevelopmental disorder caused by deficiency of the maternally expressed UBE3A gene. The UBE3A proteins functions both as an E3 ligase in the ubiquitin-proteasome system (UPS), and as a transcriptional co-activator for steroid hormone receptors. Here we investigated the effects of UBE3A deficiency on autophagy in the cerebellum of AS mice and in COS1 cells. Numbers and size of LC3- and LAMP2-immunopositive puncta were increased in cerebellar Purkinje cells of AS mice, as compared to wildtype mice. Western blot analysis showed an increase in the conversion of LC3I to LC3II in AS mice, as expected from increased autophagy. Levels of active AMPK and of one of its substrates, ULK1, a factor involved in autophagy initiation, were also increased. Colocalization of LC3 with LAMP2 was increased and p62 levels were decreased, indicating an increase in autophagy flux. UBE3A deficiency was also associated with reduced levels of phosphorylated p53 in the cytosol and increased levels in nuclei, which favors autophagy induction. UBE3A siRNA knockdown in COS-1 cells resulted in increased size and intensity of LC3-immunopositive puncta and increased the LC3 II/I ratio, as compared to control siRNA-treated cells, confirming the results found in the cerebellum of AS mice. These results indicate that UBE3A deficiency enhances autophagic activity through activation of the AMPK-ULK1 pathway and alterations in p53.

Deep learning-based facial image analysis in medical research: a systematic review protocol.

INTRODUCTION: Deep learning techniques are gaining momentum in medical research. Evidence shows that deep learning has advantages over humans in image identification and classification, such as facial image analysis in detecting people's medical conditions. While positive findings are available, little is known about the state-of-the-art of deep learning-based facial image analysis in the medical context. For the consideration of patients' welfare and the development of the practice, a timely understanding of the challenges and opportunities faced by research on deep-learning-based facial image analysis is needed. To address this gap, we aim to conduct a systematic review to identify the characteristics and effects of deep learning-based facial image analysis in medical research. Insights gained from this systematic review will provide a much-needed understanding of the characteristics, challenges, as well as opportunities in deep learning-based facial image analysis applied in the contexts of disease detection, diagnosis and prognosis. METHODS: Databases including PubMed, PsycINFO, CINAHL, IEEEXplore and Scopus will be searched for relevant studies published in English in September, 2021. Titles, abstracts and full-text articles will be screened to identify eligible articles. A manual search of the reference lists of the included articles will also be conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework was adopted to guide the systematic review process. Two reviewers will independently examine the citations and select studies for inclusion. Discrepancies will be resolved by group discussions till a consensus is reached. Data will be extracted based on the research objective and selection criteria adopted in this study. ETHICS AND DISSEMINATION: As the study is a protocol for a systematic review, ethical approval is not required. The study findings will be disseminated via peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42020196473.

With Great Hopes Come Great Expectations: Access and Adoption Issues Associated With COVID-19 Vaccines.

Although COVID-19 vaccines are becoming increasingly available, their ability to effectively control and contain the spread of the COVID-19 pandemic is highly contingent on an array of factors. This paper discusses how limitations to vaccine accessibility, issues associated with vaccine side effects, concerns regarding vaccine efficacy, along with the persistent prevalence of vaccine hesitancy among the public, including health care professionals, might impact the potential of COVID-19 vaccines to curb the pandemic. We draw insights from the literature to identify practical solutions that could boost people's adoption of COVID-19 vaccines and their accessibility. We conclude with a discussion on health experts' and government officials' moral and ethical responsibilities to the public, even in light of the urgency to adopt and endorse "the greatest amount of good for the greatest number" utilitarian philosophy in controlling and managing the spread of COVID-19.

Technology-based interventions for nursing home residents: a systematic review protocol.

INTRODUCTION: A growing number of technology-based interventions are used to support the health and quality of life of nursing home residents. The onset of COVID-19 and recommended social distancing policies that followed led to an increased interest in technology-based solutions to provide healthcare and promote health. Yet, there are no comprehensive resources on technology-based healthcare solutions that describe their efficacy for nursing home residents. This systematic review will identify technology-based interventions designed for nursing home residents and describe the characteristics and effects of these interventions concerning the distinctive traits of nursing home residents and nursing facilities. Additionally, this paper will present practical insights into the varying intervention approaches that can assist in the delivery of broad digital health solutions for nursing home residents amid and beyond the impact of COVID-19. METHODS AND ANALYSIS: Databases including the PubMed, PsycINFO, CINAHL and Scopus will be used to identify articles related to technology-based interventions for nursing home residents published between 1 January 2010 to 30 September 2021. Titles, abstracts and full-text papers will be reviewed against the eligibility criteria. The Cochrane Collaboration evaluation framework will be adopted to examine the risk of bias of the included study. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses procedures will be followed for the reporting process and implications for existing interventions and research evaluated by a multidisciplinary research team. ETHICS AND DISSEMINATION: As the study is a protocol for a systematic review, ethical approval is not required. The study findings will be disseminated via peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: CRD 42020191880.

PKA and Ube3a regulate SK2 channel trafficking to promote synaptic plasticity in hippocampus: Implications for Angelman Syndrome.

The ubiquitin ligase, Ube3a, plays important roles in brain development and functions, since its deficiency results in Angelman Syndrome (AS) while its over-expression increases the risk for autism. We previously showed that the lack of Ube3a-mediated ubiquitination of the Ca2+-activated small conductance potassium channel, SK2, contributes to impairment of synaptic plasticity and learning in AS mice. Synaptic SK2 levels are also regulated by protein kinase A (PKA), which phosphorylates SK2 in its C-terminal domain, facilitating its endocytosis. Here, we report that PKA activation restores theta burst stimulation (TBS)-induced long-term potentiation (LTP) in hippocampal slices from AS mice by enhancing SK2 internalization. While TBS-induced SK2 endocytosis is facilitated by PKA activation, SK2 recycling to synaptic membranes after TBS is inhibited by Ube3a. Molecular and cellular studies confirmed that phosphorylation of SK2 in the C-terminal domain increases its ubiquitination and endocytosis. Finally, PKA activation increases SK2 phosphorylation and ubiquitination in Ube3a-overexpressing mice. Our results indicate that, although both Ube3a-mediated ubiquitination and PKA-induced phosphorylation reduce synaptic SK2 levels, phosphorylation is mainly involved in TBS-induced endocytosis, while ubiquitination predominantly inhibits SK2 recycling. Understanding the complex interactions between PKA and Ube3a in the regulation of SK2 synaptic levels might provide new platforms for developing treatments for AS and various forms of autism.

Enhancement of synaptic plasticity and reversal of impairments in motor and cognitive functions in a mouse model of Angelman Syndrome by a small neurogenic molecule, NSI-189.

NSI-189 Phosphate, (4-benzylpiperazin-1-yl)-[2-(3-methyl-butylamino)pyridin-3-yl] methanone is a new chemical entity under development for the treatment of MDD, based upon preclinical data demonstrating stimulation of neurogenesis of human hippocampus-derived neural stem cells in vitro and in mouse hippocampus in vivo. Previous studies have examined the tolerability and efficacy of NSI-189 for treating major depressive disorder (MDD). NSI-189 has shown significant potential as a treatment for MDD, with concurrent improvement of a cognition scale in a small double-blind, placebo-controlled study. The current study evaluated its possible application for the treatment of Angelman Syndrome. Incubation of acute hippocampal slices from wild-type mice with NSI-189 resulted in a time- and dose-dependent increase in the magnitude of long-term potentiation (LTP) elicited by theta burst stimulation (TBS). The same protocol enhanced TBS-induced LTP in acute hippocampal slices from AS mice. A short treatment with daily injections of NSI-189 in AS mice reversed impairments in cognitive and motor functions, while it slightly enhanced performance of WT mice. The effects of NSI-189 on synaptic plasticity and cognitive functions were associated with activation of the TrkB and Akt pathways. These results suggest that NSI-189 could represent a potential treatment for AS patients.

Social participation and the onset of hypertension among the middle-aged and older population: Evidence from the China Health and Retirement Longitudinal Study.

AIM: While previous studies have examined the association between health-related behaviors and hypertension, comparatively little attention has been paid to the role of social participation (i.e. participating in community organizations). The aim of the present study was to investigate the longitudinal association between social participation and hypertension among the middle-aged and older population (aged ≥45 years) in China where the prevalence of hypertension has been increasing rapidly in the past few decades. METHODS: Data came from the China Health and Retirement Longitudinal Study waves 2011 and 2013. Information was obtained from 5483 participants on blood pressure, social participation and covariates. A sex-stratified Poisson regression model with a robust variance estimator was used to examine the associations. RESULTS: During the period between 2011 and 2013, 20.6% of men and 17.2% of women developed hypertension. A Poisson regression model showed that participating in community organizations once a week or more frequently was inversely associated with the onset of hypertension in women (incidence rate ratio 0.80, 95% confidence interval 0.67-0.95, P = 0.012). Among men, no such association was found. CONCLUSION: The present study suggests that promoting social participation might help mitigate the disease burden associated with hypertension in China, particularly among women. Geriatr Gerontol Int 2018; 18: 1093-1099.

UBE3A-mediated p18/LAMTOR1 ubiquitination and degradation regulate mTORC1 activity and synaptic plasticity.

Accumulating evidence indicates that the lysosomal Ragulator complex is essential for full activation of the mechanistic target of rapamycin complex 1 (mTORC1). Abnormal mTORC1 activation has been implicated in several developmental neurological disorders, including Angelman syndrome (AS), which is caused by maternal deficiency of the ubiquitin E3 ligase UBE3A. Here we report that Ube3a regulates mTORC1 signaling by targeting p18, a subunit of the Ragulator. Ube3a ubiquinates p18, resulting in its proteasomal degradation, and Ube3a deficiency in the hippocampus of AS mice induces increased lysosomal localization of p18 and other members of the Ragulator-Rag complex, and increased mTORC1 activity. p18 knockdown in hippocampal CA1 neurons of AS mice reduces elevated mTORC1 activity and improves dendritic spine maturation, long-term potentiation (LTP), as well as learning performance. Our results indicate that Ube3a-mediated regulation of p18 and subsequent mTORC1 signaling is critical for typical synaptic plasticity, dendritic spine development, and learning and memory.

Social support and care needs of the disabled elderly population: An empirical study based on survey data from Beijing, China.

In order to describe and examine differences in social support and care needs among disabled Chinese elderly, the current study used stratified sampling to survey local residents of Beijing age 60 or over in the districts of Xicheng, Chaoyang, and Tongzhou in 2016. Structured in-person interviews were conducted with a 7-domain questionnaire. Multiple logistic regressions were used to compare social support and care needs among functioning, partially disabled, and completely disabled elderly. All statistical analyses were performed using SPSS 19.0 with a significance level of 0.05 (two-sided). One thousand and eighty-three residents completed the survey. Based on Activities of Daily Living (ADL) scores, 736 (68.0%) respondents were functioning (ADL score = 14), 167 (15.4%) were partially disabled (14 < ADL score < 22), and 180 (16.6%) were fully disabled (ADL score ≥ 22). Most of the disabled had formal financial support, they received daily care at home, and they received modest emotional support. After controlling for confounding factors, fully disabled respondents were 2.35 times (p = 0.018) more likely to receive financial support and 3.65 times (p = 0.003) more likely to receive emotional support than functioning respondents. However, the fully functioning and partially disabled did not differ significantly in terms of financial or emotional support. Compared to fully functioning respondents, partially disabled respondents were 0.49 (p < 0.001) times less likely to be fully satisfied with their daily care while fully disabled respondents were 0.37 (p < 0.001) times less likely to be fully satisfied with that care. The current study provided a thorough depiction of the current status of social support and care needs of disabled Chinese elderly. More attention should be paid to social support for the partially disabled and daily care for both the partially and fully disabled.

Increasing seasonal influenza vaccination among high risk groups in China: Do community healthcare workers have a role to play?

BACKGROUND: Seasonal influenza vaccine uptake in China is low. This study aims to assess the role of community healthcare workers (HCWs) in increasing vaccination among high risk groups in China. METHODS: We analyzed data from four knowledge, attitude and practice (KAP) studies on seasonal influenza vaccination in China targeting guardians of young children, pregnant women, adults aged ≥60years, and HCWs from 2012 to 2014. RESULTS: Thirty-one percent of pregnant women and 78% adults aged ≥60years reported willingness to follow HCWs' recommendations for influenza vaccination. Guardians were more likely to vaccinate their children if they received HCWs' recommendations (35% vs. 17%, p<0.001). Community HCWs were more likely to recommend seasonal influenza vaccination than hospital HCWs (58% vs. 28%, p<0.001). CONCLUSION: Study results suggest the value of incorporating community HCWs' recommendation for seasonal influenza vaccination into existing primary public health programs to increase vaccination coverage among high risk groups in China.

Spontaneous regression of herniated lumbar discs: Report of one illustrative case and review of the literature.

Lumbar disc herniation (LDH) is a common disease that induces back pain and radicular pain. The most efficient method for the treatment of lumbar disc herniation is still controversial. Spontaneous regression of LDH has been recognized with the advancement of radiological diagnostic tools and can explain the reason of spontaneous relief of symptoms without treatment. The proposed hypotheses are; dehydration, retraction of the disc to the hernia in the annulus fibrosis, enzymatic catabolism and phagocytosis. In this study, the case of a patient with huge lumbar disc hernia regressing by itself has been presented and the potential mechanisms of disc regression have been discussed.

Effects of resveratrol on ARPE-19 cell proliferation and migration via regulating the expression of proliferating cell nuclear antigen, P21, P27 and p38MAPK/MMP-9.

AIM: To explore whether resveratrol (Res) can inhibit human retinal pigment epithelial cell (ARPE-19 cell) proliferation and migration, and to research the molecular mechanisms. METHODS: ARPE-19 cells were pretreated with various concentrations at 0, 50, 100, 150, 200 and 300 µmol/L of Res, and with 0 µmol/L Res as the control for 24, 48 and 72h. The cell proliferation, apoptosis and migration were measured with cell counting kit-8 (CCK-8), flow cytometry, and wound-healing and Transwell assays, respectively. The expression of proliferating cell nuclear antigen (PCNA), P21 and P27, as well as matrix metalloproteinase-9 (MMP-9) and p38 mitogen-activated protein kinases (p38MAPK) was identified by Western blot. RESULTS: Cell proliferation was effectively inhibited by Res (P<0.05). When pretreated with Res, cells arrested in S-phase increased remarkably (P<0.05), but the apoptosis ratios showed no significant difference between the treatment and control groups (P>0.05). Cell migration was suppressed by Res both in wound-healing assay and Transwell migration assay (P<0.05). Decreases of PCNA, MMP-9 and p38MAPK, as well as increases of P21 and P27 were detected by Western blot (P<0.05). CONCLUSION: Res can inhibit APRE-19 cell proliferation and migration in a concentration-dependent manner with up-regulation of the expression of P21 and P27, and down-regulation of PCNA, MMP-9 and p38MAPK.