Brain Delivery of Protein Therapeutics by Cell Matrix-Inspired Biomimetic Nanocarrier.

Protein therapeutics are anticipated to offer significant treatment options for central nervous system (CNS) diseases. However, the majority of proteins are unable to traverse the blood-brain barrier (BBB) and reach their CNS target sites. Inspired by the natural environment of active proteins, the cell matrix components hyaluronic acid (HA) and protamine (PRTM) are used to self-assemble with proteins to form a protein-loaded biomimetic core and then incorporated into ApoE3-reconstituted high-density lipoprotein (rHDL) to form a protein-loaded biomimetic nanocarrier (Protein-HA-PRTM-rHDL). This cell matrix-inspired biomimetic nanocarrier facilitates the penetration of protein therapeutics across the BBB and enables their access to intracellular target sites. Specifically, CAT-HA-PRTM-rHDL facilitates rapid intracellular delivery and release of catalase (CAT) via macropinocytosis-activated membrane fusion, resulting in improved spatial learning and memory in traumatic brain injury (TBI) model mice (significantly reduces the latency of TBI mice and doubles the number of crossing platforms), and enhances motor function and prolongs survival in amyotrophic lateral sclerosis (ALS) model mice (extended the median survival of ALS mice by more than 10 days). Collectively, this cell matrix-inspired nanoplatform enables the efficient CNS delivery of protein therapeutics and provides a novel approach for the treatment of CNS diseases.

Self-Disassembling and Oxygen-Generating Porphyrin-Lipoprotein Nanoparticle for Targeted Glioblastoma Resection and Enhanced Photodynamic Therapy.

The dismal prognosis for glioblastoma multiform (GBM) patients is primarily attributed to the highly invasive tumor residual that remained after surgical intervention. The development of precise intraoperative imaging and postoperative residual removal techniques will facilitate the gross total elimination of GBM. Here, a self-disassembling porphyrin lipoprotein-coated calcium peroxide nanoparticles (PLCNP) is developed to target GBM via macropinocytosis, allowing for fluorescence-guided surgery of GBM and improving photodynamic treatment (PDT) of GBM residual by alleviating hypoxia. By reducing self-quenching and enhancing lysosome escape efficiency, the incorporation of calcium peroxide (CaO2) cores in PLCNP amplifies the fluorescence intensity of porphyrin-lipid. Furthermore, the CaO2 core has diminished tumor hypoxia and improves the PDT efficacy of PLCNP, enabling low-dose PDT and reversing tumor progression induced by hypoxia aggravation following PDT. Taken together, this self-disassembling and oxygen-generating porphyrin-lipoprotein nanoparticle may serve as a promising all-in-one nanotheranostic platform for guiding precise GBM excision and empowering post-operative PDT, providing a clinically applicable strategy to combat GBM in a safe and effective manner.

Regulatory focus as a mediator in the relationship between nurses' organizational silence and professional identity.

AIMS: This work aims to analyse the current state of the professional identity of Chinese nurses; examine the relationship amongst regulatory focus, organizational silence and professional identity and determine how regulatory focus affects the relationship between professional identity and organizational silence. DESIGN: This study conducted a cross-sectional survey. METHODS: From June to August 2023, 420 nurses from six hospitals in Hunan Province, China, were selected through convenience sampling and surveyed by using a general information questionnaire, the regulatory focus scale, the organizational silence scale and the professional identity scale. The relationship amongst the regulatory focus, organizational silence and professional identity of nurses was examined by utilizing SPSS 25.0 and the mediating role of regulatory focus between organizational silence and nurses' professional identity was examined by applying AMOS 24.0. RESULTS: Nurses had a moderate level of professional identity. Professional identity was positively correlated with regulatory focus and negatively correlated with organizational silence. Regulatory focus was negatively correlated with organizational silence. Mediation effect studies revealed that organizational silence and professional identity were partially mediated by regulatory focus. CONCLUSION: In accordance with research showing that nurses' organizational silence can indirectly affect professional identity via regulatory focus, clinical nursing managers should concentrate on the interaction amongst these three variables to strengthen professional identity. IMPACT: The results of this study serve as a reminder to nurses to select a preventive or promotive focus based on their career objectives and to effectively express their views to enhance their professional identity. This also reminds nursing managers assess nurse-led regulatory focus, identify their underlying qualities and understand their professional aspirations and career orientation, create a good atmosphere for advice and encourage nurses to express their views, so as to improve nurses 'professional identity. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Intracerebral fate of organic and inorganic nanoparticles is dependent on microglial extracellular vesicle function.

Nanoparticles (NPs) represent an important advance for delivering diagnostic and therapeutic agents across the blood-brain barrier. However, NP clearance is critical for safety and therapeutic applicability. Here we report on a study of the clearance of model organic and inorganic NPs from the brain. We find that microglial extracellular vesicles (EVs) play a crucial role in the clearance of inorganic and organic NPs from the brain. Inorganic NPs, unlike organic NPs, perturb the biogenesis of microglial EVs through the inhibition of ERK1/2 signalling. This increases the accumulation of inorganic NPs in microglia, hindering their elimination via the paravascular route. We also demonstrate that stimulating the release of microglial EVs by an ERK1/2 activator increased the paravascular glymphatic pathway-mediated brain clearance of inorganic NPs. These findings highlight the modulatory role of microglial EVs on the distinct patterns of the clearance of organic and inorganic NPs from the brain and provide a strategy for modulating the intracerebral fate of NPs.

Novel use of structural equation modelling to examine diet and metabolic traits associated with microvascular endothelial dysfunction in middle-aged Chinese males: a cross-sectional study.

BACKGROUND: The present study aims to use structural equation modelling (SEM) with multiple regression pathways to examine direct and indirect links from diet and metabolic traits to microvascular endothelial dysfunction (ED) among middle-aged Chinese males. METHODS: The study was conducted in middle-aged Chinese males, who underwent a health check-up between 2018 and 2019. Data on lifestyle behaviour factors (physical activity, diet pattern, sleep quality and diet data underwent factor analysis in advance) and metabolic risk factors referring to metabolic traits were introduced into the SEM to examine inter-relationship among these factors and their association with ED, as evaluated by the reactive hyperaemia index (RHI). RESULTS: Both exploratory factor analysis and confirmatory factor analysis identified two major dietary patterns: 'prudent pattern' and 'western pattern'. The univariate test suggested that only triglycerides (TGs) and prudent dietary pattern were directly associated with RHI. Furthermore, prudent dietary pattern had an indirect association with RHI via TG (prudent diet→TG: ß=-0.15, p<0.05; TG→RHI: ß=-0.17, p<0.001). As to confirming the hypothesised association between variables apart, physical activity frequency was correlated to the decrease in TG (ß=-0.29, p<0.001), but had no direct correlation to RHI. CONCLUSION: The network of direct and indirect associations among diet pattern and cardiometabolic risk factors with RHI measured ED among middle-aged males. The most significant modifiable factors identified were TG and prudent diet pattern, which needs to be targeted as preventive strategies for early microvascular impairment.

Analysis of the incidence of falls and related factors in elderly patients based on comprehensive geriatric assessment.

Objective: To investigate the incidence of falls in elderly aged 65 years and above among outpatients and inpatients, and to analyze its related factors and identify prevention strategies. Methods: A retrospective analysis was conducted on 451 patients aged 65 years and above who received comprehensive geriatric assessment in outpatients and inpatients from the Department of Geriatrics in the Second Xiangya Hospital from March 2021 to March 2022. According to whether there had been at least one fall in the past year, the patients were divided into a fall group and a non-fall group. Data were collected from the We-Chat applet of comprehensive geriatric assessment. A t test and chi-square test were performed to compare the difference between the two groups. Logistic regression analysis was then conducted to identify factors associated with falls. Results: (1) The incidence of falls among the outpatient and inpatient was 28.8%. (2) The rate of light, moderate, and heavy dependence on daily living ability and decreased mobile balance ability were higher in the fall group than those in the non-fall group. The average calf circumference in the fall group was significantly lower than that in the non-fall group. (3) The prevalence of diabetes and eye diseases in the fall group was significantly higher than that in the non-fall group. (4) The percentage of insomnia and suspicious insomnia cases in the fall group was higher than that in the non-fall group. The mean scores for dysphagia, frailty, and incontinence were higher and the mean malnutrition score was lower in the fall group than in the non-fall group. (5) Multiple logistic regression analysis showed that frailty, insomnia, and malnutrition were independent influencing factors of fall (OR = 1.955, 1.652, 10.719, P = 0.044, 0.041, 0.025, respectively). Conclusions: The incidence of falls among outpatients and inpatients aged 65 years and above is high. Frailty, insomnia, and malnutrition are the main factors influencing falls in these patients.

Nano-Brake Halts Mitochondrial Dysfunction Cascade to Alleviate Neuropathology and Rescue Alzheimer's Cognitive Deficits.

Mitochondrial dysfunction has been recognized as the key pathogenesis of most neurodegenerative diseases including Alzheimer's disease (AD). The dysregulation of mitochondrial calcium ion (Ca2+ ) homeostasis and the mitochondrial permeability transition pore (mPTP), is a critical upstream signaling pathway that contributes to the mitochondrial dysfunction cascade in AD pathogenesis. Herein, a "two-hit braking" therapeutic strategy to synergistically halt mitochondrial Ca2+ overload and mPTP opening to put the mitochondrial dysfunction cascade on a brake is proposed. To achieve this goal, magnesium ion (Mg2+ ), a natural Ca2+ antagonist, and siRNA to the central mPTP regulator cyclophilin D (CypD), are co-encapsulated into the designed nano-brake; A matrix metalloproteinase 9 (MMP9) activatable cell-penetrating peptide (MAP) is anchored on the surface of nano-brake to overcome the blood-brain barrier (BBB) and realize targeted delivery to the mitochondrial dysfunction cells of the brain. Nano-brake treatment efficiently halts the mitochondrial dysfunction cascade in the cerebrovascular endothelial cells, neurons, and microglia and powerfully alleviates AD neuropathology and rescues cognitive deficits. These findings collectively demonstrate the potential of advanced design of nanotherapeutics to halt the key upstream signaling pathways of mitochondrial dysfunction to provide a powerful strategy for AD modifying therapy.

Comparative study on retinal microvasculature changes between acute and chronic central serous chorioretinopathy. / æ€¥æ€§ä¸Žæ ¢æ€§ä¸­å¿ƒæ€§æµ†æ¶²æ€§è„‰ç»œè†œè§†ç½‘è†œç— å˜è§†ç½‘è†œå¾®è¡€ç®¡æ”¹å˜çš„å¯¹æ¯”ç ”ç©¶.

OBJECTIVES: Central serous chorioretinopathy (CSC) is generally a common fundus disease in young and middle-aged Asian men. Acute and chronic CSC can lead to different degrees of injury to the retinal blood flow. This study aims to observe and compare the blood flow density in different retinal capillary layers in patients with acute and chronic CSC using optical coherence tomography angiography (OCTA) technology. METHODS: Twelve patients with acute CSC and 8 patients with chronic CSC including 12 eyes with acute CSC (acute CSC eye group), 11 eyes with chronic CSC (chronic CSC eye group), and 17 normal eyes (normal eye group) were enrolled in this study. All patients underwent 3 mm×3 mm, 6 mm×6 mm macular OCTA scanning. The retinal microvascu-lature was divided into superficial vascular complexes (SVC), intermediate capillary plexuses (ICP), and deep capillary plexuses (DCP) using the projection resolved-OCTA algorithm. Inner retina includes SVC, ICP, and DCP. The vessel density in each retinal layer and the inner retina were calculated and compared. RESULTS: Macular OCTA scanning of 3 mm×3 mm showed that there was no significant difference in blood flow density of SVC and ICP among the 3 groups (both P>0.05); blood flow density of DCP and inner retina in the chronic CSC eye group was significantly lower than that in the acute CSC eye group and the normal eye group (all P<0.05); there was no significant difference in retinal blood flow density of different layer between the acute CSC eye group and the normal eye group (all P>0.05). Macular OCTA scanning of 6 mm×6 mm showed that inner retinal blood flow density of the chronic CSC eye group was significantly lower than that of the acute CSC eye group and the normal eye group (both P<0.05); there was no significant difference in blood flow density of SVC among the 3 groups (P>0.05). CONCLUSIONS: The vessel density of DCP and inner retina in the eyes with chronic CSC are significantly reduced, which may result in impaired visual function. Therefore, we recommend that patients with acute CSC should be properly treated to avoid progressing into chronic CSC.

The effect of drug loading and multiple administration on the protein corona formation and brain delivery property of PEG-PLA nanoparticles.

The presence of protein corona on the surface of nanoparticles modulates their physiological interactions such as cellular association and targeting property. It has been shown that α-mangostin (αM)-loaded poly(ethylene glycol)-poly(l-lactide) (PEG-PLA) nanoparticles (NP-αM) specifically increased low density lipoprotein receptor (LDLR) expression in microglia and improved clearance of amyloid beta (Aß) after multiple administration. However, how do the nanoparticles cross the blood‒brain barrier and access microglia remain unknown. Here, we studied the brain delivery property of PEG-PLA nanoparticles under different conditions, finding that the nanoparticles exhibited higher brain transport efficiency and microglia uptake efficiency after αM loading and multiple administration. To reveal the mechanism, we performed proteomic analysis to characterize the composition of protein corona formed under various conditions, finding that both drug loading and multiple dosing affect the composition of protein corona and subsequently influence the cellular uptake of nanoparticles in b.End3 and BV-2 cells. Complement proteins, immunoglobulins, RAB5A and CD36 were found to be enriched in the corona and associated with the process of nanoparticles uptake. Collectively, we bring a mechanistic understanding about the modulator role of protein corona on targeted drug delivery, and provide theoretical basis for engineering brain or microglia-specific targeted delivery system.

Quantitative Evaluation of Retinal Microvascular Abnormalities in Patients With Type 2 Diabetes Mellitus Without Clinical Sign of Diabetic Retinopathy.

Purpose: To evaluate microvascular abnormalities in the macula and peripapillary area in diabetic patients without clinical signs of diabetic retinopathy (DR) and compare them with healthy control eyes, using optical coherence tomography angiography (OCTA). Methods: A prospective study was performed of 49 eyes from 49 diabetic patients without clinical signs of DR and a control group of 52 eyes from 52 healthy normal individuals. The 3 × 3 mm macular scans and 4.5 × 4.5 mm optic disc scans were obtained with the OCTA RTVue-XR Avanti system. Angiograms from the superficial capillary plexus, the deep capillary plexus of the macula scans, and radial peripapillary capillary plexus of the optic disc scans were analyzed with MATLAB. Multivariate binary logistic regression and the least absolute shrinkage and selection operator (LASSO) regression were used to select ideal parameters that distinguish diabetic eyes without DR from normal eyes. A receiver operating characteristic (ROC) curve was generated, and sensitivity and specificity were calculated. Results: Our final model identified FD-300 (foveal vessel density in a 300-µm-wide region around foveal avascular zone) as the only parameter selected by both the LASSO regression and the final multivariate logistic regression model that significantly differentiates diabetic eyes without clinical signs of DR from healthy normal eyes. The area under the ROC curve of FD-300 was 0.685, and sensitivity and specificity were 65.3% and 71.2%, respectively. Conclusions: Quantitative evaluation of retinal microvascular abnormalities using OCTA identified FD-300 as a useful biomarker versus the other macular and peripapillary OCTA metrics in the early detection of preclinical diabetic retinal abnormalities. Translational Relevance: OCTA may be useful in detecting early retinal microvascular abnormalities in diabetic patients before the clinical findings of DR become visible.

Physician awareness and attitudes regarding early warning score systems in mainland China: a cross-sectional study.

INTRODUCTION: The purpose of this study was to assess the application of the early warning score system (EWS-S) and gauge physician awareness, perceptions of necessity and attitudes regarding these tools based on previously experienced unnoticed clinical deterioration (CDET). METHODS: A cross-sectional survey was carried out via an online questionnaire at a large 3,500-bed Class 3A general hospital in China. A total of 299 physicians of adult general wards were asked to answer a translated questionnaire that was localised from the original version. Demographic profiles of patients were included as well as three other sections assessing awareness of CDET/EWS-S and gauging attitudes towards and perceptions of the necessity of EWS-S at our hospital. RESULTS: A high level of physician awareness of the CDET problem was observed. Most physicians knew about the existence of a systematic assessment tool for clinical application. Physicians with previous experience in reanimation, unplanned transfer to intensive care unit (UTICU) and/or death tended to consider EWS-S necessary in attentive and well-trained staff (p < 0.05). Physicians who had previous experience with UTICU were more likely to recommend implementing EWS-S in their wards compared with those without such experience (p < 0.05). CONCLUSION: Most physicians have positive attitudes towards EWS-S. However, their awareness should be further heightened. Physicians who had previous experience with CDET/UTICU were more likely to employ EWS-S in their clinical practices. To better facilitate the implementation of EWS-S in Chinese hospitals, existing facilities, policy supports, standardised managements and the development of information systems should be strengthened.

Phenotypic Spectrum of Idiopathic Hypogonadotropic Hypogonadism Patients With CHD7 Variants From a Large Chinese Cohort.

PURPOSE: Idiopathic hypogonadotropic hypogonadism (IHH) and CHARGE (C, coloboma; H, heart abnormalities; A, choanal atresia, R, retardation of growth and/or development; G, gonadal defects; E, ear deformities and deafness) syndrome are 2 distinct developmental disorders sharing features of hypogonadism and/or impaired olfaction. CHD7 variants contribute to >60% CHARGE syndrome and ~10% IHH patients. A variety of extended CHARGE-like features are frequently reported in CHARGE patients harboring CHD7 variants. In this study, we aimed to systematically analyze the diagnostic CHARGE features and the extended CHARGE-like features in patients with IHH with CHD7 variants. METHODS: Rare sequencing variants (RSVs) in CHD7 were identified through exome sequencing in 177 IHH probands. Detailed phenotyping was performed in the IHH patients harboring CHD7 variants and their available family members. RESULTS: CHD7 RSVs were identified in 10.2% (18/177) of the IHH probands. Two diagnostic CHARGE features, hearing loss and ear deformities, were significantly enriched in patients with CHD7 variants. Furthermore, CHD7 variants were significantly associated with a panel of extended CHARGE-like phenotypes, including mild ocular defects, dyspepsia/gastroesophageal reflux disease and skeletal defects. We also developed a predictive model for prioritizing CHD7 genetic testing in IHH patients. CONCLUSION: CHD7 variants rarely cause isolated IHH. Surveillance of symptoms in CHARGE syndrome-affected organs will facilitate the proper treatment for these patients. Certain clinical features can be useful for prioritizing CHD7 genetic screening.

An App-Based Intervention for Caregivers to Prevent Unintentional Injury Among Preschoolers: Cluster Randomized Controlled Trial.

BACKGROUND: App-based interventions have the potential to reduce child injury in countries with limited prevention resources, but their effectiveness has not been rigorously examined. OBJECTIVE: This study aimed to assess the effectiveness of an app-based intervention for caregivers of preschoolers to prevent unintentional injury among Chinese preschoolers. METHODS: A 6-month cluster randomized controlled trial was conducted from December 2017 to June 2018. Recruitment was conducted through preschools, which were randomly allocated to either the control group (ie, app-based parenting education excluding unintentional injury prevention) or the intervention group (ie, app-based parenting education including unintentional injury prevention). A total of 2920 caregivers of preschoolers aged 3-6 years from 20 preschools in Changsha, China, were recruited offline through the schools. The primary outcome was unintentional injury incidences among preschoolers in the past 3 months; this measure was assessed through an online caregiver-report at the baseline visit and at 3-month and 6-month follow-up visits. Secondary outcome measures included caregivers' self-reported attitudes and behaviors concerning child supervision during the last week. Generalized estimating equations (GEEs) were used to assess the effectiveness of the app-based intervention on responses at 3 and 6 months after adjusting for sociodemographic variables, baseline level of the outcome variable, and engagement with interventions in the assigned group. All analyses were intention-to-treat. A per-protocol sensitivity analysis was also conducted. RESULTS: In total, 1980 of the 2920 caregivers completed the study. The mean age of participants was 32.0 years (SD 5.5) and 68.99% (1366/1980) of them were female. During the 6-month follow-up visit, unintentional injury incidence did not change significantly in either group: incidence in the intervention group went from 8.76% (94/1073) to 8.11% (87/1073), P=.59; incidence in the control group went from 9.4% (85/907) to 7.5% (69/907), P=.15. The changes did not differ between the groups (odds ratio [OR] 1.14, 95% CI 0.80-1.62). Changes in the average score in attitude concerning unintentional injury prevention were also similar between the groups (B .05, 95% CI -0.03 to 0.13). Changes in unintentional injury prevention behaviors were greater in the intervention group than in the control group after the intervention (B .87, 95% CI 0.33-1.42). Analyses of individual injury prevention behaviors showed that the intervention reduced three risky behaviors: unsafe feeding of children (OR 0.73, 95% CI 0.60-0.89); incorrectly placing children in cars (OR 0.73, 95% CI 0.57-0.93); and allowing children to ride bicycles, electric bicycles, or motorcycles unsupervised (OR 0.80, 95% CI 0.64-0.99). The intervention also improved scores on three safety-focused behaviors: testing water temperature before giving children a bath (OR 1.26, 95% CI 1.05-1.52); properly storing sharp objects (OR 1.24, 95% CI 1.01-1.52); and safely storing medicines, detergents, and pesticides (OR 1.24, 95% CI 1.02-1.51). CONCLUSIONS: The app-based intervention did not reduce unintentional injury incidence among preschoolers but significantly improved caregivers' safety behaviors. This app-based intervention approach to improve caregiver behaviors surrounding child injury risk offers promise to be modified and ultimately disseminated broadly. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IOR-17010438; http://www.chictr.org.cn/showproj.aspx?proj=17376 (Archived by WebCite at http://www.webcitation.org/75jt17X84). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1186/s12889-018-5790-1.

Factors Associated With Dyskinesia in Parkinson's Disease in Mainland China.

Background and Objectives: Studies examining the risk factors for dyskinesia in Parkinson's disease (PD) have been inconsistent, and racial differences exist. Since there have been no systematic studies of the characteristics of dyskinesia in the Mainland Chinese population, we sought to elucidate the risk factors for dyskinesia. Methods: A total of 1974 PD patients from Mainland China were systematically investigated by univariable and multivariable analyses. PD patients with and without dyskinesia were stratified into 4 groups according to levodopa equivalent daily dose (LEDD) and analyzed by a Cox proportional hazards model. A longitudinal study of 87 patients with dyskinesia was classified into 3 groups according to the duration from onset of PD to the initiation of levodopa, and comparisons among groups were analyzed by the Mann-Whitney test. Results: Early age of onset, long disease duration, being female, high LEDD, low UPDRS III scores (ON-state) and high Hoehn-Yahr stage (ON-state) were predictors of dyskinesia. Dyskinesia was levodopa dosage-dependent, and the incidence increased remarkably when LEDD exceeded 300 mg/d (p < 0.05). The emergence of dyskinesia had no association with the initiation time of levodopa, and if the latter was more than 4 years, the duration of time on chronic levodopa free of motor complications was significantly shortened. Conclusions: We found risk factors for the prediction of dyskinesia. Our data shows that physicians should be cautious if the LEDD exceeds 300 mg/d. The development of dyskinesia was not correlated with the time of levodopa initiation.

Needs Analysis for a Parenting App to Prevent Unintentional Injury in Newborn Babies and Toddlers: Focus Group and Survey Study Among Chinese Caregivers.

BACKGROUND: With the growing popularity of mobile health technology, app-based interventions delivered by smartphone have become an increasingly important strategy toward injury prevention. OBJECTIVE: This study aimed to develop a framework supporting the design of an app-based intervention to prevent unintentional injury, targeted for caregivers of Chinese children aged 0 to 6 years. METHODS: A theory-based mixed-method study, including focus groups and Web-based quantitative survey, was performed. Adult caregivers who care for children aged 0 to 6 years and own a smartphone were recruited into 2 sequential stages of research. First, focus groups were conducted among the caregivers at community health care centers and preschools from December 2015 to March 2016. Focus groups (8-10 participants per group) explored awareness, experiences, and opinions of caregivers toward using an app to prevent unintentional injury among children. Second, based on the focus groups findings, a Web-based quantitative survey was designed and distributed to caregivers in November 2016; it collected information on specific needs for the app-based intervention. Thematic analysis and quantitative descriptive analyses were performed. RESULTS: In total, 12 focus groups were completed, involving 108 caregivers. Most participants expressed a strong desire to learn knowledge and skills about unintentional child injury prevention and held positive attitudes toward app-based interventions. Participants expressed multiple preferences concerning the app-based intervention, including their contents, functions, interactive styles, installation and registration logistics, and privacy protection and information security. Following the focus groups, 1505 caregivers completed a WeChat-based quantitative survey, which generated roughly similar results to those of focus groups and added numerical metrics concerning participants' preferences on what to learn, when to learn it, and how to learn it. A detailed framework was established involving 5 components: (1) content design, (2) functional design, (3) interactive style, (4) installation and registration logistics, and (5) privacy protection and information security, and 15 specific requirements. CONCLUSIONS: We developed a framework that can be used as a guide to design app-based interventions for parents and caregivers, specifically for unintentional injury prevention of children aged 0 to 6 years.

Correlates of Depressive Symptoms Among Older Adults With Physical Functional Limitations: A Cross-Sectional Study in China.

The current study sought to determine the prevalence and correlates of depressive symptoms among older adults with physical functional limitations in China. A total of 2,410 older adults (age ≥60 years) were enrolled. Depressive symptoms and physical function were assessed with the Patient Health Questionnaire-9 (PHQ-9) and Barthel Index of Activities of Daily Living, respectively. Univariate logistic regression and stepwise multiple logistic regression analyses were performed. The mean score for depressive symptoms was 5.45 (SD = 5.49), with a prevalence of 27% (95% confidence interval [25.2, 28.8]). Risk factors for depressive symptoms included female gender, rural residence, being a farmer before age 60, history of chronic disease, self-reported poor health status, complete dependence, stressful life events over the past 3 months, insufficient emotional and material support, and low social participation over the past 1 month and feeling depressed about it. However, individuals older than 80 with high educational levels and hobbies showed a relatively low prevalence of depressive symptoms compared to their counterparts. This study confirms the necessity to screen for depressive symptoms in older adults, particularly those with physical functional limitations. The information can be used to identify and reduce related risk factors of depressive symptoms for vulnerable older adults. [Res Gerontol Nurs. 2019; 12(3):133-146.].

Effectiveness of an app-based intervention for unintentional injury among caregivers of preschoolers: protocol for a cluster randomized controlled trial.

BACKGROUND: Each year, over 15,000 preschoolers die from unintentional injuries in China. Many interventions proven to work in other nations have not been implemented nationwide in China. The rapid popularity of smartphones offers an opportunity to overcome this limitation and disseminate evidence-based interventions to the large population of China. This study aims to assess the effectiveness of an app-based intervention for caregivers of preschoolers to prevent unintentional injury among young Chinese children. METHOD: A single-blinded, 6-month, parallel-group cluster randomized controlled trial with 1:1 allocation ratio will be conducted in Changsha, China. In total, 2626 caregivers of preschoolers ages 3-6 years old who own a smartphone will be recruited from 20 preschools. Clusters will be randomized at the preschool level and allocated to either the control group (routine education plus app-based parenting education excluding unintentional injury prevention) or the intervention group (routine education plus app-based parenting education including unintentional injury prevention). The app-based injury prevention program was developed based on the Theory of Planned Behavior, the Haddon Matrix, the Mobile Learning framework, and a needs assessment. Data collection will be conducted at baseline, 3-month, and 6-month follow-up via app-based survey plus printed questionnaire survey. The primary outcome measure is unintentional injury incidence among preschoolers in the past 3 months. Secondary outcome measures include economic losses due to unintentional injury in the past 3 months, the Incremental Cost-Effectiveness Ratios (ICERs), and parent's attitudes and behaviors concerning supervision to prevent preschooler unintentional injury in the past week. An intention-to-treat approach will be used to evaluate outcome measures. Chi-square tests will examine differences for outcome measures between groups at each time point and generalized estimation equations (GEE) will test the overall effectiveness of the app-based intervention. Missing outcome data will be imputed using the Expectation Maximization algorithm (EM). DISCUSSION: This trial will examine evidence concerning the effectiveness of an innovative app-based intervention for caregivers of Chinese preschoolers. If effective, the app-based intervention could offer an effective population-based intervention option to cost-effectively promote unintentional injury prevention in countries and regions where injury control is under-supported. TRIAL REGISTRATION: ChiCTR-IOR-17010438 . Registered 15 January 2017.

Which type of congenital malformations is significantly increased in singleton pregnancies following after in vitro fertilization/intracytoplasmic sperm injection: a systematic review and meta-analysis.

It is inconclusive nowadays for which type of congenital malformations(CMs) is increased in singleton pregnancies following after in vitro fertilization(IVF)/intracytoplasmic sperm injection(ICSI) compared with those after spontaneous conception; furthermore, a complete overview is missing. We conducted a meta-analysis of cohort studies to assess the risk of specific CMs associated with IVF/ICSI singleton pregnancies. Unrestricted searches were conducted, with an end date parameter of 1 June 2017, of PubMed, Embase, Google Scholar, Cochrane Libraries, and Chinese databases. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup and sensitivity analyses were performed to explore potential heterogeneity moderators when significant heterogeneity was observed. Sixteen cohort studies with a total of 129,648 IVF/ICSI and 5,491,949 spontaneously conceived singleton births fulfilled the inclusion criteria. The IVF/ICSI singleton pregnancies had a significantly increased risk of cleft lip and/or palate (OR = 1.34 [95% CI: 1.07-1.69]; I2 = 0%), eye, ear, face and neck (odd ratios [OR] = 1.20 [95% CI: 1.04-1.39]; I2 = 15%), chromosomal (OR = 1.23 [95% CI: 1.07-1.40]; I2 = 32%), respiratory (OR = 1.28 [95% CI: 1.01-1.64]; I2 = 37%), digestive (OR = 1.46 [95% CI: 1.29-1.65]; I2 = 0%), musculoskeletal (OR = 1.47 [95% CI: 1.25-1.72]; I2 = 64%), urogenital (OR = 1.43 [95% CI: 1.18-1.72]; I2 = 62%), and circulatory (OR = 1.39 [95% CI: 1.23-1.58]; I2 = 46%) system malformations. Relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded consistent results. No evidence of publication bias was observed. In conclusion, the IVF/ICSI singleton pregnancies are associated with higher risks for most specific CMs. Clinicians should provide appropriate information to counseling IVF/ICSI patients.

The contribution of GIGYF2 to Parkinson's disease: a meta-analysis.

The contribution of the gene of GIGYF2, Grb10-Interacting GYF Protein 2, to Parkinson's disease (PD) is still ambiguous. To explore the contribution of GIGYF2 to PD at the genetic level, we analyzed the relationship between all reported GIGYF2 variants (including mutations and polymorphisms) and PD through a meta-analysis. Databases including Medline, Embase, etc., were searched to find relevant studies. All eligible publications have to meet the strict inclusion and exclusion criteria listed. Two authors independently selected trials, assessed the article's quality and extracted data. Odds ratios (ORs) and relative risks with 95 % confidence intervals (CIs) were used to evaluate the strength of associations. All analyses were carried out by using the Review Manager software package v.5.2. More than 100 variants of GIGYF2 were reported either or both in patients and controls in 10 included publications. The 10 publications totally included 5466 patients and 6517 controls. We conducted meta-analyses for the following variants: N56S, N457T, Del LPQQQQQQ 1209-1216, Del Q 1210 (rs10555297), rs12328151, rs2289912, rs2305138, rs3816334, A572A and H1171R. The ORs for N56S were 2.86 (95 % CI 1.10, 7.41) for PD and 4.75 (95 % CI 1.35, 16.68) for FPD. And the OR for N457T in FPD was 4.53 (95 % CI 1.04, 19.66). On the other hand, other variants involved in meta-analyses were not related to PD. This research results suggest that the N56S and N457T of GIGYF2 are risk factors for PD in Caucasians, but not in Asians.

[Knowledge, attitude and behavior on blood lipid among people participated in health examination in Changsha and the influential factors].

OBJECTIVE: To evaluate the knowledge, attitude and behavior on blood lipid among people in Changsha and to provide evidences for prevention and control of blood lipid abnormality. METHODS: A total of 400 cases were randomly selected on the questionnaire of the knowledge, attitude and behavior on blood lipid in ordinary adults who participate in health examination in Xiangya Hospital. Blood lipid related physical examination was conducted at the same time. The health examination participants were divided into several groups according to their sex, age, degree of education, marriage and family income. The influential factors for knowledge, attitude and behavior were analyzed. RESULTS: The knowledge score of blood lipid for health examination participants was 18.33±8.67 (total score 37), the attitude score was 6.63±2.45 (total score 9) and the behavior score was 8.32±2.65 (total score 16). The scores of female was higher than that of male in the terms of knowledge and behavior (both P< 0.05); the scores in the 40-49 age group were lower than those in the other age groups (all P< 0.05); the scores in the junior high school group were lower than those in the other education groups (all P< 0.05); the scores in the family group with less than 2 000 yuan income were lower than those in other family groups with different income (all P< 0.05). The multiple stepwise regression analysis showed that: 1) the knowledge on blood lipid score was influenced by ages and education background (both P< 0.05); 2) while the attitude of blood lipid was influenced by four factors such as education background, systemic blood pressure, blood sugar and triglyceride(all P< 0.05); 3) the behavior on blood lipid was influenced by five factors such education background, triglyceride, systemic blood pressure, blood sugar and ages (all P< 0.05). CONCLUSION: The knowledge, attitude and behavior on blood lipid among health examination participants were mostly influenced by education background, gender and ages. Thus, clinical medical staff should prevent the blood lipid abnormality through the health education and improve the knowledge in normal people. The group of 40-49 age male should be thought as the primary intervention subjects. The knowledge, attitude and behavior on blood lipid among the general population is also related to individual's blood pressure, blood sugar and triglyceride. So the clinical medical staff should also improve the knowledge of blood lipid, blood pressure and blood sugar in general population for improving their attitude and unhealthy habits. In addition, the active control of blood sugar and blood pressure can enhance the overall health status of the general population.