Effectiveness of a government-led, multiarm intervention on early childhood development and caregiver mental health: a study protocol for a factorial cluster-randomised trial in rural China.

INTRODUCTION: The high incidences of both the developmental delay among young children and the mental health problems of their caregivers are major threats to public health in low-income and middle-income countries. Parental training interventions during early childhood have been shown to benefit early development, yet evidence on strategies to promote caregiver mental health remains limited. In addition, evidence on the optimal design of scalable interventions that integrate early child development and maternal mental health components is scarce. METHODS AND ANALYSIS: We design a single-blind, factorial, cluster-randomised controlled, superiority trial that will be delivered and supervised by local agents of the All China Women's Federation (ACWF), the nationwide, government-sponsored social protection organisation that aims to safeguard the rights and interests of women and children. We randomise 125 villages in rural China into four arms: (1) a parenting stimulation arm; (2) a caregiver mental health arm; (3) a combined parenting stimulation and caregiver mental health arm and (4) a pure control arm. Caregivers and their children (aged 6-24 months at the time of baseline data collection) are selected and invited to participate in the 12-month-long study. The parenting stimulation intervention consists of weekly, one-on-one training sessions that follow a loose adaptation of the Reach Up and Learn curriculum. The caregiver mental health intervention is comprised of fortnightly group activities based on an adaptation of the Thinking Healthy curriculum from the WHO. Primary outcomes include measures of child development and caregiver mental health. Secondary outcomes include a comprehensive set of physical, psychological and behavioural outcomes. This protocol describes the design and evaluation plan for this programme. ETHICS AND DISSEMINATION: This study received approval from the Institutional Review Board of Stanford University (IRB Protocol #63680) and the Institutional Review Board of the Southwestern University of Finance and Economics in Chengdu, Sichuan, China. Informed oral consent will be obtained from all caregivers for their own and their child's participation in the study. The full protocol will be publicly available in an open-access format. The study findings will be published in economics, medical and public health journals, as well as Chinese or English policy briefs. TRIAL REGISTRATION NUMBER: AEA RCT Registry (AEARCTR-0010078) and ISRCTN registry (ISRCTN84864201).

Academic Performance and the Link with Depressive Symptoms among Rural Han and Minority Chinese Adolescents.

The objectives of this paper were to examine the risk of depression and depressive symptoms among Han and minority children and adolescents in rural China, the links between academic performance and depressive symptoms, and the prevalence of these links among specific subgroups. A total of 8392 4th, 5th, and 6th grade students at 105 sample rural schools in eight low-income counties and districts in a prefectural-level city in Southwestern China were randomly selected using a three-step sampling strategy. A total of 51% of the sample were female (SD = 0.50), and the age range was 7 to 19 years (mean = 11.35 years; SD = 1.05). Using the Patient Health Questionnaire 8-item depression scale, the prevalence of depressive symptoms in the sample was assessed, while data on students' academic performance (standardized math test) and demographic characteristics were also collected. Our results show that the rates of major depression were 19% for Han students, 18% for Tibetan students, and 22% for Yi students; the rates of severe depression were 2% for Han and Tibetan students, and 3% for Yi students. Yi students were at significantly higher risks for major and severe depression than Han students. We conducted multivariate regression and heterogeneous analyses. Academic performance was negatively and significantly correlated to depressive symptoms. Across the whole sample, students with lower math scores, minority students, boys, younger students, and students with migrant parents were most vulnerable to depressive symptoms. The heterogeneous analysis suggests that among poor-performing students, subgroups at higher risk for depression include boys, non-boarding students, and students whose mothers had graduated from high school or above. These findings indicate a need to improve mental health outcomes of rural Han and minority primary school students, targeting academic performance for possible intervention.

Repressor element-1 silencing transcription factor regulates glutamate receptors and immediate early genes to affect synaptic plasticity.

OBJECTIVE: This study aimed to investigate the regulatory effects of repressor element-1 silencing transcription factor (REST) on the glutamate receptors and immediate early genes (IEGs) in the SH-SY5Y cells. METHODS: The genes regulated by REST were screened by bioinformatics between AD patients and the control group. Then, SH-SY5Y cells were treated with 10 µM Aß or REST siRNA/cDNA, and the expressions of synaptic genes and IEGs were detected. Moreover, the protein expression of synaptophysin and PSD-95 was detected by Western blotting in the primary mouse hippocampal neurons. RESULTS: Firstly, 464 differentially expressed genes regulated by REST were identified between Alzheimer's disease (AD) patients and controls, and REST was closely related to the glutamatergic synapses and long-term potentiation. GRIA1, GRIN2A, GRIN1, and ARC showed significant variations with the changes of REST. Moreover, the loss of REST reduced the expression of synaptophysin and PSD-95, which was related to synaptic plasticity. CONCLUSION: REST maintains synaptic plasticity by affecting both glutamate receptors and IEGs, and the imbalance between neural excitation and inhibition mediated by REST compromises neural function, contributing to cognitive impairment.

Effects of Berberine on Circular RNA Expression Profiles in Human Gastric Cancer Cells.

BACKGROUND: Berberine has been demonstrated to have anticancer effects against gastric cancer (GC), but the mechanism of these actions is unclear. OBJECTIVES: To explore the impact of berberine on circular RNA (circRNA) expression profiles in GC and investigate the potential molecular mechanisms associated with circRNAs in GC. METHODS: AGS and HGC27 GC cells were treated with various concentrations of berberine. Cell viability was measured using a Cell Counting Kit-8 assay. Cell proliferation was measured using a cell colony formation assay. Cell apoptosis was measured using flow cytometry. The mitochondrial membrane potential (Δψm) was determined using a JC-1 probe. RNA-seq was performed to identify circRNA expression profiles in AGS cells after berberine treatment. Selected differentially expressed (DE) circRNAs were verified using RT-qPCR. Bioinformatics analysis was performed to predict target miRNAs and mRNAs and construct a circRNA-miRNA-mRNA network. Pathway and process enrichment analyses were performed to explore the potential biological roles of DE circRNAs. RESULTS: Berberine decreased GC cell viability, cell proliferation, and Δψm and induced cell apoptosis. Thirty-one DE circRNAs were identified in the berberine-treated group compared to the control group, among which circRNA2499, hsa_circ_0003423, and hsa_circ_0006702 were validated using RT-qPCR. Enrichment analyses, based on the host genes of these 31 DE circRNAs and putative target mRNAs in the circRNA-miRNA-mRNA network of the validated circRNAs, indicated that berberine exerts anti-GC effects in multiple pathways including the Notch, MAPK, and NF-κB signaling pathways via specific circRNAs. CONCLUSION: This study elucidated the expression profile of circRNAs in human GC cells after berberine treatment. Our results demonstrate that berberine has the potential to influence cancer-related pathways by regulating circRNA expression and their corresponding target genes in GC cells.

CD4+CD25+ Regulatory T Cells in Intracranial Thrombi Are Inversely Correlated with Hemorrhagic Transformation after Thrombectomy: A Clinical-Immunohistochemical Analysis of Acute Ischemic Stroke.

Mechanical thrombectomy is not only effective for managing patients with acute ischemic stroke (AIS), but it also enables a valuable histological analysis of thrombi. Previous studies indicated that regulatory T cells (Treg) adoptive transfer might alleviate the hemorrhagic transformation. However, whether Treg in intracranial thrombi correlates with hemorrhagic transformation after mechanical thrombectomy remains unclear. This study mainly analyzed the colocation of Treg markers in serial thrombus sections stained serially for CD4 and CD25 in groups of hemorrhagic or nonhemorrhagic transformation. Second, to investigate whether these immunohistochemical parameters could provide any additional information beyond hemorrhagic transformation, we compared the overlap between Treg markers among other groups, such as functional outcomes, stroke subtypes, and gender. Our results showed that the number of CD4+CD25+ Treg cells was lower in the hemorrhagic transformation thrombi than in the nonhemorrhagic group (p < 0.001) but there were no significant differences otherwise. The present finding of CD4+CD25+ Treg cell reductions in thrombi associated with hemorrhagic transformation provides the histological evidence supporting that thromboinflammation might involve in the pathological process of an acute stroke after mechanical thrombectomy.

Long-Term Safety and Efficacy of Antiplatelet Therapy in Patients With Cerebral Infarction With Thrombocytopenia.

This study aimed to investigate the long-term safety and benefits of antiplatelet therapy in patients with cerebral infarction with thrombocytopenia, as evidence regarding this was limited. This cohort trial assessed patients with acute cerebral infarction with thrombocytopenia treated in the Neurology Department of Shanghai Tenth People's Hospital from January 2016 to December 2018, and enrolled patients were followed up for 9 months. The patients were divided into non-antiplatelet and antiplatelet groups based on the actual intake of antiplatelet drugs. Primary endpoints included hemorrhagic events, recurrence of cerebral infarction, and activity of daily living (ADL) score changes. To balance baseline clinical data, propensity score matching was applied, and there were finally 65 matched patients, including 30 and 35 in the antiplatelet and non-antiplatelet groups, respectively. There were no differences in hemorrhagic and cerebral infarction recurrence rates between the 2 groups. ADL score change was higher in the antiplatelet group than in the non-antiplatelet group (10 vs 5, p = 0.039). In multivariate regression analysis, antiplatelet therapy significantly predicted a positive change in ADL scores [B = 8.381, 95% confidence interval (0.56-16.19)]. In patients with acute cerebral infarction with thrombocytopenia, antiplatelet therapy could the improve the quality of life in the chronic stage.

The Impact of Repeated Exposure to Items.

THEORY: When test developers have a limited number of test questions available or when the equating design requires some item overlap across forms, psychometricians worry that examinees who encounter previously seen questions on subsequent test forms may be able to inflate their test score due to their familiarity with the repeated test questions. HYPOTHESES: Prior exposure to test questions may lead to contamination and inflated scores. This research seeks to detect if examinees' scores were inflated due to prior exposure to test questions and, if so, whether those increases were significant. METHOD: The sample for this study consisted of candidates who took the American Board of Family Medicine's certification examination twice in a single year (n = 988). Examinees were randomly assigned one of two forms for their first attempt and received the other form for their repeat test. There were 99 questions in common across both forms. The Rasch model was used to estimate examinee ability. Performance changes on the common questions and unique questions were compared and repeated measures t tests were performed to establish whether score changes were likely to have occurred by chance. RESULTS: On average, the examinees increased their overall ability estimate by .187 logits on the repeat attempt. The repeated measures t tests indicate this difference was statistically significant, t(987) = -25.298, p < .001, α = .05. The mean difference between the examinees' ability estimate on common and unique items for their first attempt was not statistically significant, t(987) = .264, p = .792, α = .05; however, the mean difference between common and unique items on the second attempt (0.029 logits) was statistically significant, t(987) = 3.28, p = .001, α = .05. CONCLUSIONS: Some of the increase in the examinees' overall ability estimate may attributed to a general increase in the latent trait; however, there was a small but detectable increase that could be attributed to prior exposure to the questions. On average, about 15% of the repeated questions were changed from wrong to right, but about 11% of questions were changed from right to wrong, suggesting that examinees may occasionally be using prior exposure to their benefit but general guessing accounts for more of the changes. The impact of the mean difference between the common and unique item scores (0.029 logits) is trivial at the individual level; however, such a bias among the population of repeat testers could be problematic if a small subset of examinees were using a "remember-research-retest" strategy to obtain nontrivial score increases.