Different Safety Pattern of an Inactivated SARS-CoV-2 Vaccine (CoronaVac®) According to Age Group in a Pediatric Population from 3 to 17 Years Old, in an Open-Label Study in Chile.

During the COVID-19 pandemic, the importance of vaccinating children against SARS-CoV-2 was rapidly established. This study describes the safety of CoronaVac® in children and adolescents between 3- and 17-years-old in a multicenter study in Chile with two vaccine doses in a 4-week interval. For all participants, immediate adverse events (AEs), serious AEs (SAEs), and AEs of special interest (AESIs) were registered throughout the study. In the safety subgroup, AEs were recorded 28 days after each dose. COVID-19 surveillance was performed throughout the study. A total of 1139 individuals received the first and 1102 the second dose of CoronaVac®; 835 were in the safety subgroup. The first dose showed the highest number of AEs: up to 22.2% of participants reported any local and 17.1% systemic AE. AEs were more frequent in adolescents after the first dose, were transient, and mainly mild. Pain at the inoculation site was the most frequent AE for all ages. Fever was the most frequent systemic AE for 3-5 years old and headache in 6-17 years old. No SAEs or AESIs related to vaccination occurred. Most of the COVID-19 cases were mild and managed as outpatients. CoronaVac® was safe and well tolerated in children and adolescents, with different safety patterns according to age.

Iruplinalkib (WX­0593), a novel ALK/ROS1 inhibitor, overcomes crizotinib resistance in preclinical models for non-small cell lung cancer.

Despite remarkable initial responses of anaplastic lymphoma kinase (ALK) inhibitors in ALK-positive non-small cell lung cancer (NSCLC) patients, cancers eventually develop resistance within one to two years. This study aimed to compare the properties of iruplinalkib (WX­0593) with other ALK inhibitors and report the comprehensive characterization of iruplinalkib against the crizotinib resistance. The inhibitory effect of iruplinalkib on kinase activity was detected. A kinase screen was performed to evaluate the selectivity of iruplinalkib. The effect of iruplinalkib on related signal transduction pathways of ALK and c-ros oncogene 1 (ROS1) kinases was examined. The cellular and in vivo activities of ALK inhibitors were compared in engineered cancer-derived cell lines and in mice xenograft models, respectively. Human hepatocytes derived from three donors were used for evaluating hepatic enzyme inducing activity. HEK293 cell lines expressing transportors were used to invesigated the drug interaction potential mediated by several transporters. The results showed iruplinalkib potently inhibited the tyrosine autophosphorylation of wild-type ALK, ALKL1196M, ALKC1156Y and epidermal growth factor receptor (EGFR)L858R/T790M. The inhibitory effects of iruplinalkib in patient-derived xenograft and cell line-derived xenograft models were observed. Moreover, iruplinalkib showed robust antitumor effects in BALB/c nude mice xenograft models with ALK-/ROS1-positive tumors implanted subcutaneously, and the tumor suppressive effects in crizotinib-resistant model was significantly better than that of brigatinib. Iruplinalkib did not induce CYP1A2, CYP2B6 and CYP3A4 at therapeutic concentration, and was also a strong inhibitor of MATE1 and MATE2K transporters, as well as P-gp and BCRP. In conclusion, iruplinalkib, a highly active and selective ALK/ROS1 inhibitor, exhibited strong antitumor effects in vitro and in crizotinib-resistant models.

Association of adenosine triphosphate-related genes to major depression and suicidal behavior: Cognition as a potential mediator.

BACKGROUND: Soluble epoxide hydrolase (sEH, encoded by EPHX2) and P2X2 (a subtype of ATP receptors) may mediate the antidepressant-like effects of ATP. We sought to determine whether polymorphisms and mRNA expression of EPHX2 and P2X2 are associated with depression and suicidal behavior and how cognition may mediate such associations. METHOD: We examined 83 single nucleotide polymorphisms (SNPs) of EPHX2 and P2X2. Subjects were MDD suicide attempters (N = 143), MDD non-suicide attempters (N = 248), and healthy volunteers (HV, N = 110). Data on demographics, depression severity, and suicide attempts were collected. Participants completed a set of cognitive tasks. Polymorphisms were genotyped using MALDI-TOF MS within the MassARRAY system. The expression of mRNA was measured using real-time polymerase chain reaction (RT-PCR). RESULTS: Cognitive function was a significant mediator (p = 0.006) of the genetic effect on depression. Allele C of rs202059124 was associated with depression risk (OR = 11.57, 95%CI: 2.33-209.87, p = 0.0181). A significant relationship was found between P2X2 mRNA expression and depression (OR = 0.68, 95%CI: 0.49-0.94, p = 0.0199). One haploblock (rs9331942 and rs2279590) was associated with suicide attempts: subjects with haplotype GC (frequency = 19.8 %, p = 0.017) and AT (frequency = 35.2 %, p < 0.001) had a lower rate of suicide attempts. CONCLUSIONS: Our results confirmed that cognitive impairment plays a role in the effect of rs9331949 on depression. Moreover, we confirmed a relationship between P2X2, EPHX2, and MDD in humans and presented preliminary haplotype-based evidence that implicates EPHX2 in suicide. LIMITATIONS: The main limitation of this study is the limited sample size. More comprehensive and multi-domain cognition tasks and different assessment measures are required in further study.

Inactivated Vaccine-Induced SARS-CoV-2 Variant-Specific Immunity in Children.

Multiple vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been evaluated in clinical trials. However, trials addressing the immune response in the pediatric population are scarce. The inactivated vaccine CoronaVac has been shown to be safe and immunogenic in a phase 1/2 clinical trial in a pediatric cohort in China. Here, we report interim safety and immunogenicity results of a phase 3 clinical trial for CoronaVac in healthy children and adolescents in Chile. Participants 3 to 17 years old received two doses of CoronaVac in a 4-week interval until 31 December 2021. Local and systemic adverse reactions were registered for volunteers who received one or two doses of CoronaVac. Whole-blood samples were collected from a subgroup of 148 participants for humoral and cellular immunity analyses. The main adverse reaction reported after the first and second doses was pain at the injection site. Four weeks after the second dose, an increase in neutralizing antibody titer was observed in subjects relative to their baseline visit. Similar results were found for activation of specific CD4+ T cells. Neutralizing antibodies were identified against the Delta and Omicron variants. However, these titers were lower than those for the D614G strain. Importantly, comparable CD4+ T cell responses were detected against these variants of concern. Therefore, CoronaVac is safe and immunogenic in subjects 3 to 17 years old, inducing neutralizing antibody secretion and activating CD4+ T cells against SARS-CoV-2 and its variants. (This study has been registered at ClinicalTrials.gov under no. NCT04992260.) IMPORTANCE This work evaluated the immune response induced by two doses of CoronaVac separated by 4 weeks in healthy children and adolescents in Chile. To date, few studies have described the effects of CoronaVac in the pediatric population. Therefore, it is essential to generate knowledge regarding the protection of vaccines in this population. Along these lines, we reported the anti-S humoral response and cellular immune response to several SARS-CoV-2 proteins that have been published and recently studied. Here, we show that a vaccination schedule consisting of two doses separated by 4 weeks induces the secretion of neutralizing antibodies against SARS-CoV-2. Furthermore, CoronaVac induces the activation of CD4+ T cells upon stimulation with peptides from the proteome of SARS-CoV-2. These results indicate that, even though the neutralizing antibody response induced by vaccination decreases against the Delta and Omicron variants, the cellular response against these variants is comparable to the response against the ancestral strain D614G, even being significantly higher against Omicron.

Thematic trends and knowledge structure on cognitive behavior therapy for insomnia: A bibliometric and visualization analysis.

Objective: To find publications trend about cognitive behavior therapy for insomnia (CBTI) using bibliometric and visualization analysis. In this study, the authors sought to identify the publication trends of peer-reviewed articles about CBTI. Materials and methods: Analyses were focused on the past 18 years from 2004 to 2021. All searches were performed on the Web of Science Core Collection database. The search was repeated to include structural cognitive behavior therapy for insomnia. Quantitative analysis was assessed using the bibliometric tool. Visualization analysis was carried out using VOSviewer. Results: In the 736 articles reviewed, the number of publications has been increasing every year for the past 18 years. Behavioral sleep medicine and sleep were the most active journals published on CBTI. The United States and Canada had the highest scientific publications in the field. Morin CM and Espie CA were the most active authors. The study type mostly observed were randomized controlled trials, meta-analyses, and epidemiological. Publications on digital-based cognitive behavior therapy and accessibility to primary care settings represent the future trends of research on CBTI. Conclusion: Possible explanations for CBTI publication trends were discussed, including the emergence of the evidence-based therapy, feasibility, and scalability. Potential CBTI publications trends in the future and clinical implications were also discussed.

Can cognition help predict suicide risk in patients with major depressive disorder? A machine learning study.

BACKGROUND: Previous studies suggest that deficits in cognition may increase the risk of suicide. Our study aims to develop a machine learning (ML) algorithm-based suicide risk prediction model using cognition in patients with major depressive disorder (MDD). METHODS: Participants comprised 52 depressed suicide attempters (DSA) and 61 depressed non-suicide attempters (DNS), and 98 healthy controls (HC). All participants were required to complete a series of questionnaires, the Suicide Stroop Task (SST) and the Iowa Gambling Task (IGT). The performance in IGT was analyzed using repeated measures ANOVA. ML with extreme gradient boosting (XGBoost) classification algorithm and locally explanatory techniques assessed performance and relative importance of characteristics for predicting suicide attempts. Prediction performances were compared with the area under the curve (AUC), decision curve analysis (DCA), and net reclassification improvement (NRI). RESULTS: DSA and DNS preferred to select the card from disadvantageous decks (decks "A" + "B") under risky situation (p = 0.023) and showed a significantly poorer learning effect during the IGT (F = 2.331, p = 0.019) compared with HC. Performance of XGBoost model based on demographic and clinical characteristics was compared with that of the model created after adding cognition data (AUC, 0.779 vs. 0.819, p > 0.05). The net benefit of model was improved and cognition resulted in continuous reclassification improvement with NRI of 5.3%. Several clinical dimensions were significant predictors in the XGBoost classification algorithm. LIMITATIONS: A limited sample size and failure to include sufficient suicide risk factors in the predictive model. CONCLUSION: This study demonstrate that cognitive deficits may serve as an important risk factor to predict suicide attempts in patients with MDD. Combined with other demographic characteristics and attributes drawn from clinical questionnaires, cognitive function can improve the predictive effectiveness of the ML model. Additionally, explanatory ML models can help clinicians detect specific risk factors for each suicide attempter within MDD patients. These findings may be helpful for clinicians to detect those at high risk of suicide attempts quickly and accurately, and help them make proactive treatment decisions.

Six-month follow-up of a booster dose of CoronaVac in two single-centre phase 2 clinical trials.

Determining the duration of immunity induced by booster doses of CoronaVac is crucial for informing recommendations for booster regimens and adjusting immunization strategies. In two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials, immunogenicity and safety of four immunization regimens are assessed in adults aged 18 to 59 years and one immunization regimen in adults aged 60 years and older, respectively. Serious adverse events occurring within 6 months after booster doses are recorded as pre-specified secondary endpoints, geometric mean titres (GMTs) of neutralising antibodies one year after the 3-dose schedule immunization and 6 months after the booster doses are assessed as pre-specified exploratory endpoints, GMT fold-decreases in neutralization titres are assessed as post-hoc analyses. Neutralising antibody titres decline approximately 4-fold and 2.5-fold from day 28 to day 180 after third doses in adults aged 18-59 years of age and in adults aged 60 years and older, respectively. No safety concerns are identified during the follow-up period. There are increases in the magnitude and duration of humoral response with homologous booster doses of CoronaVac given 8 months after a primary two-dose immunization series, which could prolong protection and contribute to building our wall of population immunity. Trial number: NCT04352608 and NCT04383574.

Brain-wide projection reconstruction of single functionally defined neurons.

Reconstructing axonal projections of single neurons at the whole-brain level is currently a converging goal of the neuroscience community that is fundamental for understanding the logic of information flow in the brain. Thousands of single neurons from different brain regions have recently been morphologically reconstructed, but the corresponding physiological functional features of these reconstructed neurons are unclear. By combining two-photon Ca2+ imaging with targeted single-cell plasmid electroporation, we reconstruct the brain-wide morphologies of single neurons that are defined by a sound-evoked response map in the auditory cortices (AUDs) of awake mice. Long-range interhemispheric projections can be reliably labelled via co-injection with an adeno-associated virus, which enables enhanced expression of indicator protein in the targeted neurons. Here we show that this method avoids the randomness and ambiguity of conventional methods of neuronal morphological reconstruction, offering an avenue for developing a precise one-to-one map of neuronal projection patterns and physiological functional features.

Influence of the GABA Receptor Subunit Gene Polymorphism and Childhood Sexual Abuse on Processing Speed in Major Depression and Suicide Attempt.

Background: Suicide is moderately heritable and also more common in those who report childhood abuse. Previously, it was found that allele A of GABRG2 (GABA A receptor subunit gamma2) polymorphism rs211034 was protective in a suicide attempt (SA). Hence, it was proposed that rs211034 may interact with childhood trauma to influence cognitive deficits related to SA or depression risk. Genetic variants may predict the benefits of certain cognitive treatments. Methods: A total of 52 individuals who had attempted suicide, 59 individuals with major depressive disorder (MDD) or bipolar depression who had not previously attempted suicide, and 90 healthy volunteers were subjected to the modified Suicide Stroop task and were clinically assessed using the Childhood Trauma Questionnaire (CTQ) and Hamilton Depression Scale-24 items (HAMD-24). rs211034 was genotyped using Sanger sequencing. Results: After correcting for covariates, depressed participants displayed longer reaction times for all emotional conditions, including suicide-related words, compared with healthy controls. Depressed suicide attempters displayed longer reaction times for negative words than depressed non-attempters. Depressed non-attempters displayed higher interference scores for negative words compared with healthy controls. There was an interaction between rs211034 risk allele and the effects of reported childhood sexual abuse (CSA) on reaction time for all emotional words and suicide-related words. Carriers of the rs211034 risk allele A exhibited shorter reaction times, but the protective effects of this allele were eliminated in those exposed to reported CSA. Conclusion: Only limited results were found regarding effects of a past suicide attempt on response times to emotional and suicide-related words, but there was an overall effect of major depression on slower response time. Protective genetic effects of the rs211034 A allele on this slowing were eliminated in those with a history of sexual abuse during childhood. Further research is needed to better characterize the mechanisms underlying the effects of childhood trauma on these genetic effects.

Relationship between suicide rate and antidepressant prescription: An ecological study in the People's Republic of China.

OBJECTIVES: The objective of this study was to estimate the features of suicide rate and its association with antidepressant prescriptions during the past decade in China. METHODS: Official data on suicides were obtained and stratified by four age groups, gender, urban/rural areas, and regions (East, Central, and West). The annual antidepressant prescriptions were expressed in pills per 100 persons calculated as the volume of prescriptions divided by the total population. Negative binomial regression was carried out to examine the association between suicide and other variables. RESULTS: Suicide rates in each stratum typically decreased from 2008 to 2015, while annual antidepressant prescriptions were generally increased by the year. The suicide rate increased with age and was greater in adult males than in females; higher in the central area and greater in rural than in urban areas. Suicide rates are negatively associated with antidepressant prescriptions including selective serotonin reuptake inhibitors (Incidence rate ratio [IRR] 0.983, 95% confidence interval [CI] 0.983-0.983), serotonin-norepinephrine reuptake inhibitors (IRR 0.951, 95% CI 0.951-0.951), tricyclic antidepressant (IRR 0.925, 95% CI 0.925-0.925) and total antidepressants (IRR 0.990, 95% CI 0.990-0.990) during 2008-2012. CONCLUSION: Suicide varied among different studied stratum. Suicide rates are negatively associated with antidepressant prescriptions.

Double-Blind, Randomized, Placebo-Controlled Phase III Clinical Trial to Evaluate the Efficacy and Safety of treating Healthcare Professionals with the Adsorbed COVID-19 (Inactivated) Vaccine Manufactured by Sinovac - PROFISCOV: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: To evaluate the efficacy of two doses of the adsorbed vaccine COVID-19 (inactivated) produced by Sinovac in symptomatic individuals, with virological confirmation of COVID-19, two weeks after the completion of the two-dose vaccination regimen, aged 18 years or older who work as health professionals providing care to patients with possible or confirmed COVID-19. To describe the occurrence of adverse reactions associated with the administration of each of two doses of the adsorbed vaccine COVID-19 (inactivated) produced by Sinovac up to one week after vaccination in Adults (18-59 years of age) and Elderly (60 years of age or more). TRIAL DESIGN: This is a Phase III, randomized, multicenter, endpoint driven, double-blind, placebo-controlled clinical trial to assess the efficacy and safety of the adsorbed vaccine COVID-19 (inactivated) produced by Sinovac. The adsorbed vaccine COVID-19 (inactivated) produced by Sinovac (product under investigation) will be compared to placebo. Voluntary participants will be randomized to receive two intramuscular doses of the investigational product or the placebo, in a 1: 1 ratio, stratified by age group (18 to 59 years and 60 years or more) and will be monitored for one year by active surveillance of COVID-19. Two databases will be established according to the age groups: one for adults (18-59 years) and one for the elderly (60 years of age or older). The threshold to consider the vaccine efficacious will be to reach a protection level of at least 50%, as proposed by the World Health Organization and the FDA. Success in this criterion will be defined by sequential monitoring with adjustment of the lower limit of the 95% confidence interval above 30% for the primary efficacy endpoint. PARTICIPANTS: Healthy participants and / or participants with clinically controlled disease, of both genders, 18 years of age or older, working as health professionals performing care in units specialized in direct contact with people with possible or confirmed cases of COVID-19. Participation of pregnant women and those who are breastfeeding, as well as those intending to become pregnant within three months after vaccination will not be allowed. Participants will only be included after signing the voluntary Informed Consent Form and ensuring they undergo screening evaluation and conform to all the inclusion and exclusion criteria. All the clinical sites are located in Brazil. INTERVENTION AND COMPARATOR: Experimental intervention: The vaccine was manufactured by Sinovac Life Sciences (Beijing, China) and contains 3 µg/0.5 mL (equivalent to 600 SU per dose) of inactivated SARS-CoV-2 virus, and aluminium hydroxide as adjuvant. Control comparator: The placebo contains aluminium hydroxide in a 0.5 mL solution The schedule of both, experimental intervention and placebo is two 0.5 mL doses IM (deltoid) with a two week interval. MAIN OUTCOMES: The primary efficacy endpoint is the incidence of symptomatic cases of virologically confirmed COVID-19 two weeks after the second vaccination. The virological diagnosis will be confirmed by detection of SARS-CoV-2 nucleic acid in a clinical sample. The primary safety endpoint is the frequency of solicited and unsolicited local and systemic adverse reactions during the period of one week after vaccination according to age group in adult (18-59 years old) and elder (60 years of age or older) subjects. Adverse reactions are defined as adverse events that have a reasonable causal relationship to vaccination. RANDOMISATION: There will be two randomization lists, one for each age group, based on the investigational products to be administered, i.e., vaccine or placebo at a 1: 1 ratio. Each randomization list will be made to include up to 11,800 (18-59 year-old) adults, and 1,260 elderly (60 y-o and older) participants, the maximum number of participants needed per age group. An electronic central randomization system will be used to designate the investigational product that each participant must receive. BLINDING (MASKING): This trial is designed as a double-blind study to avoid introducing bias in the evaluation of efficacy, safety and immunogenicity. The clinical care team, the professionals responsible for the vaccination and the participants will not know which investigational product will be administered. Only pharmacists or nurses in the study who are responsible for the randomization, separation and blinding of the investigational product will have access to unblinded information. The sponsor's operational team will also remain blind. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The total number of participants needed to evaluate efficacy, 13,060 participants, satisfies the needed sample size calculated to evaluate safety. Therefore, the total number obtained for efficacy will be the number retained for the study. Up to 13,060 participants are expected to enter the study, with up to 11,800 participants aged 18 to 59 years and 1,260 elderly participants aged 60 and over. Half of the participants of each group will receive the experimental vaccine and half of them will receive the placebo. The recruitment of participants may be modified as recommended by the Data Safety Monitoring Committee at time of the interim unblinded analysis or blind assessment of the COVID-19 attack rate during the study. TRIAL STATUS: Protocol version 2.0 - 24-Aug-2020. Recruitment started on July 21st, 2020. The recruitment is expected to conclude in October 2020. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT0445659 . Registry on 2 July 2020 FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Neutralizing Antibody Responses to Severe Acute Respiratory Syndrome Coronavirus 2 in Coronavirus Disease 2019 Inpatients and Convalescent Patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a pandemic with no specific antiviral treatments or vaccines. There is an urgent need for exploring the neutralizing antibodies from patients with different clinical characteristics. METHODS: A total of 117 blood samples were collected from 70 COVID-19 inpatients and convalescent patients. Antibodies were determined with a modified cytopathogenic neutralization assay (NA) based on live severe acute respiratory syndrome coronavirus 2 and enzyme-linked immunosorbent assay (ELISA). The dynamics of neutralizing antibody levels at different time points with different clinical characteristics were analyzed. RESULTS: The seropositivity rate reached up to 100.0% within 20 days since onset, and remained 100.0% till days 41-53. The total geometric mean titer was 1:163.7 (95% confidence interval [CI], 128.5-208.6) by NA and 1:12 441.7 (95% CI, 9754.5-15 869.2) by ELISA. The antibody level by NA and ELISA peaked on days 31-40 since onset, and then decreased slightly. In multivariate generalized estimating equation analysis, patients aged 31-45, 46-60, and 61-84 years had a higher neutralizing antibody level than those aged 16-30 years (ß = 1.0470, P = .0125; ß = 1.0613, P = .0307; ß = 1.3713, P = .0020). Patients with a worse clinical classification had a higher neutralizing antibody titer (ß = 0.4639, P = .0227). CONCLUSIONS: The neutralizing antibodies were detected even at the early stage of disease, and a significant response was shown in convalescent patients.

Interactions of the GABRG2 polymorphisms and childhood trauma on suicide attempt and related traits in depressed patients.

BACKGROUND: Previously, we reported that the longest variant of the GABA A receptor γ2 subunit (GABRG2) was associated with suicidal behavior. The present study therefore aimed to determine whether polymorphisms near the alternatively spliced exon of GABRG2 are associated with suicide attempt (SA) and its related traits, and how these variants might interact with reported childhood trauma (CT) in their association with suicidal behavior. METHODS: We examined 5 single nucleotide polymorphisms (SNPs) of GABRG2. Subjects were suicide Attempters (N = 94), non-suicide attempters (N = 168) with MDD or Bipolar depression, and healthy volunteers (N = 100). Data on demographics, depression severity and suicide attempts were collected. Participants also completed a set of instruments assessing CT, and lifetime aggression and impulsivity.. GABRG2 polymorphisms were genotyped using Sanger sequencing. RESULTS: Allele A of rs211034 was a protective factor for SA (OR = 0.50 (0.32, 0.80), p = 0.003), and had an interaction effect with emotional neglect (OR = 0.89 (0.82, 0.97), p = 0.006) on depression. One haploblock (consisting of rs211035 and rs211034) was identified within these SNPs, and subjects with haplotype GA (frequency = 7.3%), had lower rate of SA (OR=0.26(0.10, 0.67), p = 0.006). Cognitive impulsivity (OR=1.38)1.24,1.55), p < 0.001), non-planning impulsivity (OR = 1.18 (1.10,1.25), p < 0.001), anger (OR = 1.13 (1.07,1.19), p < 0.001), impulsivity total score (OR = 1.10(1.06,1.15), p < 0.001), hostility (OR = 1.10 (1.04, 1.15), p < 0.001), aggression total score (OR = 1.05 (1.03,1.07), p < 0.001) were associated with depression, meanwhile, hopelessness (OR = 2.18 (1.56, 3.04), p < 0.001) and impulsivity total score (OR = 1.05 (1.02,1.08), p < 0.001) were associated with the risk of SA, adjusted by age and gender. There was no mediation effect in the relationship among CT, gene polymorphisms and SA or depression through increased impulsivity or aggression. LIMITATIONS: The main limitation of this study is its modest sample size. More genetic variants as well as epigenetic markers should be examined in future studies. CONCLUSIONS: These findings add to evidence for the involvement of GABRG2 and impulsivity and hopelessness in SA independent from their association with depression. More research is needed on possible mediators of the relationship between GABA-related gene and SA.

Socioeconomic status moderates the association between patient satisfaction with community health service and self-management behaviors in patients with type 2 diabetes: A cross-sectional survey in China.

The objective of this study was to examine the association between patient satisfaction with community health service (CHS) and self-management behaviors in patients with type 2 diabetes mellitus (T2DM).In all, 1691 patients with T2DM from 8 community health centers in 5 provinces in China participated in the present study. The dependent variables included 4 measures of self-management behaviors: regular self-monitoring of blood glucose (SMBG), prescribed medication adherence, recommended dietary changes, and regular exercise. The independent variable was patient satisfaction with CHS. Multivariable logistic regression models were performed to examine the association between patient satisfaction with CHS and self-management behaviors.The mean satisfaction score in the participants was 3.14 (out of a maximum of 5). After adjusting for covariates including demographic factors, health status, health knowledge, and socioeconomic status (SES), diabetic patients with high CHS satisfaction had better medication adherence (odds ratio [OR] 1.25, 95% confidence interval [CI] 1.02-1.55), increased exercise management (OR 1.19, 95% CI 1.06-1.35), and more SMBG (OR 1.16, 95% CI 1.03-1.32); all these associations varied across SES groups. The association between satisfaction and medication adherence was significant among participants younger than 65 years with lower education (OR 2.15, 95% CI 1.37-3.37), income (OR 1.62, 95% CI 1.13-2.32), and lower-status occupations (OR 1.69, 95% CI 1.16-2.47). Among participants younger than 65 years and had lower education attainment, the association between satisfaction and diet management was observed. There were positive associations between satisfaction and regular exercise among subgroups of participants younger than 65 years, except for lower education group. A significant association between satisfaction and SMBG among participants ≥65 years old, who also had lower SES and higher-status occupations, was also observed.The study findings suggested that T2DM patient satisfaction with CHS was moderate. High satisfaction with CHS indicated better medication adherence, exercise management, and SMBG, and these associations varied by SES.

The effectiveness of hypertension management in China: a community-based intervention study.

AIM: This study aimed to evaluate the effectiveness of hypertension management and analyse the factors associated with blood pressure reduction within China's primary healthcare system. BACKGROUND: Hypertension is one of the leading risk factors for global disease burden and is strongly associated with cardiovascular diseases. In China, hypertension is a serious public health problem, but few studies have evaluated the effectiveness of hypertension management in China's primary healthcare system. METHODS: The study sites were 24 primary healthcare institutions, selected using multistage stratified random sampling method. In each institution, hypertension patients aged at least 35 years who agreed to participate and had no disabilities or mental health problems were enrolled for hypertension management. Participants received comprehensive interventions in the primary healthcare system via a team. After a one-year intervention, data from 6575 hypertension patients were analysed to check the effectiveness of hypertension management and examined factors associated with hypertension control. FINDINGS: There was an overall mean reduction of 4.5 mmHg in systolic blood pressure (SBP) and 1.9 mmHg in diastolic blood pressure (DBP). The blood pressure reduction after one year was greater in rural patients than in urban patients, 6.6 mmHg versus 3.4 mmHg for SBP and 2.6 mmHg versus 1.6 mmHg for DBP, respectively. The hypertension control rate also increased more in rural areas (22.1%) than in urban areas (10.6%) after the one-year intervention. Age, body mass index, region and being in an urban area had a significant negative association with the reduction of SBP (P < 0.05). Education level and baseline SBP showed a significant positive association (P < 0.05). CONCLUSIONS: Community-based hypertension management by general practitioners was feasible and effective. The effectiveness of hypertension management in rural areas was greater than in urban areas. Intervention strategies should pay more attention to patients in rural areas and western China.

Effect of immunonutrition on colorectal cancer patients undergoing surgery: a meta-analysis.

PURPOSE: Immunonutrition has been used to prevent the complications after colorectal elective surgery. This systematic review aimed to analyze and assess the effect of immunonutrition on colorectal cancer patients who received elective surgery. METHODS: Three electronic databases (Medline, Embase, Cochrane) were used to search the latent studies which investigated the effects of enteral immunonutrition (EIN) compared with standard enteral nutrition (EN) or parenteral immunonutrition (PIN) compared with standard parenteral nutrition (PN) on colorectal cancer patients who are undergoing surgery until 21st of April, 2017. Meta-analysis was conducted to calculate odd risk (OR), mean difference (MD), or standard mean difference (SMD) with 95% confidence interval (CI), and heterogeneity was tested by Q test. RESULTS: Nine publications were included. The meta-analysis results presented that EIN improved the length of hospital stay (pooled MD, 2.53; 95% CI, 1.29-3.41), infectious complications (pooled OR, 0.33; 95% CI, 0.21-0.53) which contains the Surgical Site Infections (pooled OR, 0.25; 95% CI, 0.22-0.58) and Superficial/Deep incisional infections (pooled OR, 0.27; 95% CI, 0.12-0.64); meanwhile, PIN improved the length of hospital stay (pooled MD, 2.66; 95% CI, 0.62-4.76), IL-6 (pooled MD, - 6.09; 95% CI, - 10.11 to - 2.07), CD3 (pooled MD, 7.50; 95% CI, 3.57-11.43), CD4 (pooled MD, 5.47; 95% CI, 2.54-8.40), and CD4/CD8 (pooled MD, 0.50; 95% CI, 0.22-0.78); the level of CD8 was lower (pooled MD, - 4.32; 95% CI, - 7.09 to - 1.55) in PIN. CONCLUSION: Immunonutrition could be an effective approach to enhance the immune function of colorectal cancer patients undergoing elective surgery and to improve the clinical and laboratory outcomes.

Prevalence of Anemia and its Risk Factors among Children under 36 Months Old in China.

This study aims to evaluate the prevalence and sociodemographic factors of anemia in children <36 months old in China. In this study, data of 24 235 children were investigated from 32 primary health care (PHC) facilities in 11 province-level regions. Pearson χ2-test and logistic regression model were used to estimate potential risk factors associated with anemia. The overall prevalence of anemia was 24.4%, and 32.8% children from rural areas were anemic, but no statistically significant difference was observed between male and female. Predictors of anemia are different regions of China, cesarean delivery, premature birth and neonatal asphyxia. We also found that education level and income of children's parents are important determinants of childhood anemia. In additional, feeding practice would affect anemia among children aged 6-12 months. Our results could provide some insights for prevention and control of childhood anemia in PHC facilities.

An economic-research-based approach to calculate community health-staffing requirements in Xicheng District, Beijing.

BACKGROUND: A shortage of community health professionals has been a crucial issue hindering the development of CHS. Various methods have been established to calculate health workforce requirements. This study aimed to use an economic-research-based approach to calculate the number of community health professionals required to provide community health services in the Xicheng District of Beijing and then assess current staffing levels against this ideal. METHODS: Using questionnaires, we collected relevant data from 14 community health centers in the Xicheng District, including resident population, number of different health services provided, and service volumes. Through 36 interviews with family doctors, nurses, and public health workers, and six focus groups, we were able to calculate the person-time (equivalent value) required for each community health service. Field observations were conducted to verify the duration. RESULTS: In the 14 community health centers in Xicheng District, 1752 health workers were found in our four categories, serving a population of 1.278 million. Total demand for the community health service outstripped supply for doctors, nurses, and public health workers, but not other professionals. The method suggested that to properly serve the study population an additional 64 family doctors, 40 nurses, and 753 public health workers would be required. CONCLUSIONS: Our calculations indicate that significant numbers of new health professionals are required to deliver community health services. We established time standards in minutes (equivalent value) for each community health service activity, which could be applied elsewhere in China by government planners and civil society advocates.

Antibiotic misuse among children with diarrhea in China: results from a national survey.

BACKGROUND: Antibiotic resistance is one of the world's biggest public health issues, and the situation in China is particularly grave. The objective of this study is to investigate the antibiotics usage pattern among Chinese children and provide further insight in developing strategies for promoting public health education. METHODS: This is a cross-sectional study, in the study, participants are from 53,665 guardians of children aged 0-6 years, who were recruited with multistage stratified random cluster sampling in 2013/2014 from 46 community health centers in 14 provinces across China Mainland. Children's guardians completed surveys on their previous experience on using antibiotics in treating diarrhea of their children without a prescription from any pediatrician. Odds ratios (ORs) and 95% confidential intervals (CIs) for the association between antibiotic use and its predictors were estimated using multilevel logistic regression models, with antibiotic rational use group as a reference group. RESULTS: The prevalence of antibiotic misuse among children with diarrhea in the eastern, middle and western areas of China and associations between antibiotic misuse and its predictors were studied. The average rate of antibiotic misuse is 35.12%. Multilevel logistic regression revealed that living in urban areas (OR = 0.79 (0.76, 0.83)), female children (OR = 0.92 (0.88, 0.96)), guardians having higher education (OR = 0.60 (0.55, 0.66)), being raised by parents (OR = 0.90 (0.85, 0.94)), guardians having basic health knowledge (OR = 0.82 (0.79, 0.86)) are protective factors and children's age (1-3 years OR = 1.62 (1.54, 1.71)); 4-6 years OR = 1.90 (1.77, 2.03)) is a risk factor of antibiotic misuse among children aged 0-6 years with diarrhea in China. CONCLUSIONS: Our findings confirmed that there has been a high rate of antibiotic misuse without a prescription in children with diarrhea in China, which requires considerable attention. Suitable regulations and interventions are needed to solve this problem.

Magnetically separable and recyclable Fe3O4-polydopamine hybrid hollow microsphere for highly efficient peroxidase mimetic catalysts.

Magnetic Fe3O4-polydopamine (PDA) hybrid hollow microspheres, in which Fe3O4 nanoparticles were firmly incorporated in the cross-linked PDA shell, have been prepared through the formation of core/shell PS/Fe3O4-PDA composites based on template-induced covalent assembly method, followed by core removal in a tetrahydrofuran solution. The morphology, composition, thermal property and magnetic property of the magnetic hybrid hollow microspheres were characterized by SEM, TEM, FT-IR, XRD, TGA, and vibrating sample magnetometer, respectively. Results revealed that the magnetic hybrid hollow microspheres had about 380 nm of inner diameter and about 30 nm of shell thickness, and 13.6 emu g(-1) of magnetization saturation. More importantly, the Fe3O4-PDA hybrid hollow microspheres exhibited intrinsic peroxidase-like activity, as they could quickly catalyze the oxidation of typical substrates 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide. Compared with PDA/Fe3O4 composites where Fe3O4 nanoparticles were loaded on the surface of PDA microspheres, the stability of Fe3O4-PDA hybrid hollow microspheres was greatly improved. As-prepared magnetic hollow microspheres might open up a new application field in biodetection, biocatalysis, and environmental monitoring.