The role of leptin in ischemic stroke and its subtypes: A Mendelian randomization study.

BACKGROUND AND AIMS: Observational studies have suggested a relationship between leptin and risk of stroke. However, evidence for the association remains inconsistent, and whether the association reflects a causal relationship remains to be established. To clarify this relationship, we adopted a two-sample Mendelian randomization (MR) analysis to investigate whether leptin plays a causal role in the risk of stroke and its subtypes. METHODS AND RESULTS: Five independent single-nucleotide polymorphisms (SNPs) associated with the leptin level from genome-wide association studies (GWASs) of European individuals were selected. We performed an MR analysis using the inverse-variance-weighted (IVW) as primary method to examine the causal effects of leptin on ischemic stroke (IS). Moreover, MR-Egger intercept and Cochran's Q statistic were also performed to detect the pleiotropy or heterogeneity of our MR results. Genetically predicted circulating leptin level was not associated with ischemic stroke [odds ratio (OR): 1.48, 95% confidence interval (CI): 0.78-2.8, P = 0.22], large artery stroke (OR: 1.44, 95% CI: 0.39-5.25, P = 0.57), cardioembolic stroke (OR:1.33, 95% CI: 0.55-3.22, P = 0.52), and small vessel stroke (OR: 1.48, 95% CI: 0.39-5.63, P = 0.56) using the IVW method. Likewise, there is no convincing evidence for the associations between leptin levels and cardiovascular diseases (CVD) risk factors. CONCLUSIONS: This study did not provide evidence that leptin levels are associated with increased risk of stroke and its subtypes.

Sleep structure assessed by objective measurement in patients with mild cognitive impairment: A meta-analysis.

OBJECTIVES: A meta-analysis was used to explore the characteristic changes in objective sleep structure of patients with mild cognitive impairment (MCI) compared with cognitively healthy older adults. MATERIALS AND METHODS: PubMed, EMBAS, Cochrane Library, Scopus, and Web of Science were searched until November 2023. A literature quality evaluation was performed according to the Newcastle-Ottawa Scale, and a meta-analysis was performed by RevMan 5.3 software. RESULTS: Fifteen studies with 771 participants were finally included. Compared with normal control groups, patients with MCI had a decreased total sleep time by 34.44 min, reduction in sleep efficiency by 7.96 %, increased waking after sleep onset by 19.61 min, and increased sleep latency by 6.97 min. Ten included studies showed that the patients with MCI had increased N1 sleep by 2.72 % and decreased N3 sleep by 0.78 %; however, there was no significant difference between the MCI and control groups in percentage of N2 sleep. Moreover, Twelve included studies reported the MCI groups had shorter REM sleep of 2.69 %. CONCLUSION: Our results provide evidence of abnormal sleep architecture in patients with MCI. As a "plastic state," abnormal sleep architecture may be a promising therapeutic target for slowing cognitive decline and dementia prevention.

A network analysis of anxiety and depression symptoms in Chinese disabled elderly.

BACKGROUND: Mental health is an essential dimension of healthy aging. The number and severity of disabled elderly in China show an increasing tendency year by year. Due to their impaired ability of daily activities, reduced social participation and reduced self-care ability, they are more prone to depression and anxiety. METHOD: We included 2131 individuals aged 65 and older from the Chinese Longitudinal Healthy Longevity Survey (CLHLS 2017-2018). We used the 10-item Center for Epidemiologic Studies Depression Scale (CESD-10) and the Generalized Anxiety Disorder scale-7 (GAD-7) to assess depression and anxiety, respectively. The structure of depressive and anxiety symptoms was characterized using "Expected Influence" and "Bridge Expected Influence" as centrality indices in the symptom network. Network stability was tested using a case-dropping bootstrap procedure. Finally, a Network Comparison Test (NCT) was conducted to examine whether network characteristics differed by gender. RESULTS: Network analysis revealed that nodes CESD3 (Felt sadness), GAD2 (Uncontrollable worry), and GAD4 (Trouble relaxing) were the primary symptoms of the anxiety-depression network. Anxiety and depression were united by the symptoms of CESD9 (Could not get going), GAD1 (Nervousness or anxiety), CESD10 (Sleep quality), and GAD4 (Trouble relaxing). Additionally, Gender did not significantly affect the network structure. CONCLUSION: Central symptoms (e.g., felt sadness, uncontrollable worry and trouble relaxing) and key bridge symptoms (e.g., could not get going, nervousness and anxiety) in the depressive and anxiety symptoms network may be used as potential targets for intervention among disabled elderly who is at risk for or suffer from depressive and anxiety symptoms.

Development and psychometric appraisal of Head Nurse Research Leadership Scale.

AIM: To develop a Head Nurse Research Leadership Scale and evaluate its reliability and validity. DESIGN: A psychometric instrument validation study was conducted in two phases. METHODS: The item tool was generated based on a literature review, semi-structured interview and brainstorming. Twenty experts validated the content of the initial version for two rounds. Thirty-nine clinical nurses conducted the HNRLS-v3 to test the readability of the items in pilot study I. Items were screened based on the critical ratio, correlation coefficient analysis, Cronbach's α coefficient and factor analysis using the data collected from 265 nurses in pilot study II. A cross-sectional survey was conducted in six hospitals to evaluate the reliability and validity between 4 January 2022 and 15 January 2022. Three hundred and sixteen nurses participated in this survey, and 60 completed the questionnaire to validate the test-retest reliability between 1 February and 6 February. RESULTS: A 15-item Head Nurse Research Leadership Scale based on 5 dimensions was developed, and the content validity was satisfied. The 15 items accounted for 77.9% of the variance. Confirmatory factor analysis showed acceptable convergent validity and discriminant validity. The Cronbach's α coefficient, split-half reliability and test-retest reliability of the scale were 0.966, 0.9633 and 0.927, respectively.

Nursing adherence, barriers and facilitators to conduct post-stroke dysphagia screening and assessment: A study based on theoretical domain framework.

BACKGROUND: There are an increasing number of evidence-based recommendations for managing dysphagia in post-stroke patients. However, it is unclear whether nurses adopt these recommendations in their daily nursing practices. AIMS: This study aimed to explore nurses' adherence, barriers, facilitators and views on dysphagia screening and assessment of post-stroke dysphagia. METHODS: In this study, multiple methods were adopted. In Phase 1, a general information questionnaire and a knowledge-attitude-practice and barriers/facilitators questionnaire for dysphagia screening and assessment were distributed in 55 hospitals online. In Phase 2, semi-structured interviews were conducted to explore nurses' views on barriers. Descriptive and one-way variance analyses were used to analyse the quantitative data, while content analysis was used to analyse the qualitative data. This study adheres to STROBE and COREQ guidelines. RESULTS: Nine hundred and forty-two completed questionnaires were collected. Only 36.52% of the nurses screened for swallow function in patients as a guideline. The biggest barrier was 'memory, attention and decision process', with an average score of 3.22 (.74). The different stages of implementation had various types and degrees of barriers (p < .001). Five themes were extracted after interviews, namely 'Inadequate environment and resource support', 'Increased workload', 'Professional value perception', 'Organisational culture', and 'Poor knowledge and skill'. CONCLUSIONS: Nurses' practice of dysphagia screening and assessment of patients with dysphagia after stroke were inadequate, and the barriers originated from patients, leadership and the nurses themselves. RELEVANCE TO CLINICAL PRACTICE: This research extracted five barriers of guidance adherence for post-stroke dysphagia screening and assessment and identified the different kinds and degrees of barriers in five implementation stages, providing a basis for nursing managers to break through the bottleneck of guideline implementation. PATIENT OR PUBLIC CONTRIBUTION: The nurses recruited in this study completed validated questionnaires in the survey and suggestive answers in interviews.

Validation of Fitbit Charge 4 for assessing sleep in Chinese patients with chronic insomnia: A comparison against polysomnography and actigraphy.

Our research aims to assess the performance of a new generation of consumer activity trackers (Fitbit Charge 4TM: FBC) to measure sleep variables and sleep stage classifications in patients with chronic insomnia, compared to polysomnography (PSG) and a widely used actigraph (Actiwatch Spectrum Pro: AWS). We recruited 37 participants, all diagnosed with chronic insomnia disorder, for one night of sleep monitoring in a sleep laboratory using PSG, AWS, and FBC. Epoch-by-epoch analysis along with Bland-Altman plots was used to evaluate FBC and AWS against PSG for sleep-wake detection and sleep variables: total sleep time (TST), sleep efficiency (SE), waking after sleep onset (WASO), and sleep onset latency (SOL). FBC sleep stage classification of light sleep (LS), deep sleep (DS), and rapid eye movement (REM) was also compared to that of PSG. When compared with PSG, FBC notably underestimated DS (-41.4, p < 0.0001) and SE (-4.9%, p = 0.0016), while remarkably overestimating LS (37.7, p = 0.0012). However, the TST, WASO, and SOL assessed by FBC presented no significant difference from that assessed by PSG. Compared with PSG, AWS and FBC showed great accuracy (86.9% vs. 86.5%) and sensitivity (detecting sleep; 92.6% vs. 89.9%), but comparatively poor specificity (detecting wake; 35.7% vs. 62.2%). Both devices showed better accuracy in assessing sleep than wakefulness, with the same sensitivity but statistically different specificity. FBC supplied equivalent parameters estimation as AWS in detecting sleep variables except for SE. This research shows that FBC cannot replace PSG thoroughly in the quantification of sleep variables and classification of sleep stages in Chinese patients with chronic insomnia; however, the user-friendly and low-cost wearables do show some comparable functions. Whether FBC can serve as a substitute for actigraphy and PSG in patients with chronic insomnia needs further investigation.

Resampling-based cost loss attention network for explainable imbalanced diabetic retinopathy grading.

Diabetic retinopathy (DR) is currently considered to be one of the most common diseases that cause blindness. However, DR grading methods are still challenged by the presence of imbalanced class distributions, small lesions, low accuracy of small sample classes and poor explainability. To address these issues, a resampling-based cost loss attention network for explainable imbalanced diabetic retinopathy grading is proposed. First, the progressively-balanced resampling strategy is put forward to create a balanced training data by mixing the two sets of samples obtained from instance-based sampling and class-based sampling. Subsequently, a neuron and normalized channel-spatial attention module (Neu-NCSAM) is designed to learn the global features with 3-D weights and a weight sparsity penalty is applied to the attention module to suppress irrelevant channels or pixels, thereby capturing detailed small lesion information. Thereafter, a weighted loss function of the Cost-Sensitive (CS) regularization and Gaussian label smoothing loss, called cost loss, is proposed to intelligently penalize the incorrect predictions and thus to improve the grading accuracy of small sample classes. Finally, the Gradient-weighted Class Activation Mapping (Grad-CAM) is performed to acquire the localization map of the questionable lesions in order to visually interpret and understand the effect of our model. Comprehensive experiments are carried out on two public datasets, and the subjective and objective results demonstrate that the proposed network outperforms the state-of-the-art methods and achieves the best DR grading results with 83.46%, 60.44%, 65.18%, 63.69% and 92.26% for Kappa, BACC, MCC, F1 and mAUC, respectively.

Influence of peers' actual appraisals on moral self-representations of Chinese adolescents.

Adolescence is a vital period of developing a moral self. As individuals enter adolescence, peers become increasingly important to them. This study aimed to explore the influence of peers' actual appraisals on moral self-representations. Based on Looking Glass Self Hypothesis, peers' reflected appraisals usually have a mediating effect on peers' actual appraisals and self-appraisals. This study used the Chinese Moral Trait Words Rating Scale to investigate 160 dyads of Chinese adolescents (12-14 years old). The participants filled in the Self-Appraisals Questionnaire, Peers' Reflected Appraisals Questionnaire, and Peers' Actual Appraisals Questionnaire, respectively. The results showed that: (a) peers' actual appraisals indirectly affected self-appraisals through peers' reflected appraisals in the process of forming the moral self of early Chinese adolescents; (b) Chinese adolescents had a certain accuracy in peers' actual appraisals, but often underestimated their peers' actual appraisals of them. This study was conducive to understanding the influence of peers on forming adolescents' moral self in the context of collectivistic culture.

A prospective interventional study of recombinant human interleukin-11 mouthwash in chemotherapy-induced oral mucositis.

BACKGROUND: This prospective interventional study aimed to evaluate and analyse the efficacy of rhIL-11 mouthwash compared to Kangfuxin fluid in treatment and blank control in prevention of oral mucositis (OM) in patients receiving chemotherapy. MATERIALS AND METHODS: In total, 50 patients in the treatment group and 62 patients in the prevention group were included. Subsequently, each group was divided into an experimental group and a control group. In the treatment group, the experimental patients received recombinant human interleukin-11 (rhIL-11) mouthwash, whereas the control group received Kangfuxin fluid. In the prevention group, experimental patients still received rhIL-11 mouthwash based on routine oral care, whereas the control group only received routine oral care. Meanwhile, we observed and recorded the efficacy in the treatment group, and the occurrence and grades of OM in the prevention group. RESULTS: Through statistical analysis, the results showed that on the seventh day of treatment, the experimental group showed more improvement compared to the control group, and it was statistically significant (p = 0.032). The average healing time in the experimental group (3.59 ± 1.927 days) was shorter than that in the control group (4.96 ± 2.421 days; p = 0.031). In the prevention group, we observed the incidence of oral mucositis. No significant differences were found in the occurrence and grades of OM in the experimental and control groups (p = 0.175). CONCLUSION: Our preliminary results indicate that rhIL-11 mouthwash may be a superior option to treat OM, especially in severe cases, compared to Kangfuxin fluid. However, there is no advantage in prevention.

Exploring Psychoneurological Symptom Clusters in Acute Stroke Patients: A Latent Class Analysis.

Purpose: To identify latent classes of acute stroke patients with distinct experiences with the symptom clusters of depression, anxiety, fatigue, sleep disturbance, and pain symptoms and assess, if the selected variables determine a symptom-cluster experience in acute stroke patients. Participants and Methods: A sample of 690 participants were collected from July 2020 to December 2020 in a cross-sectional descriptive study. Latent class analysis was conducted to distinguish different clusters of acute stroke participants who experienced five patient-reported symptoms. Furthermore, multinomial logistic regression was selected to verify the influencing indicators of each subgroup, with selected socio-demographic variables, clinical characteristics, self-efficacy, and perceived social support as independent variables and the different latent classes as the dependent variable. Results: Three latent classes, named "all high symptom," "high psychological disorder," and "all low symptom," were identified, accounting for 9.6%, 26.3%, and 64.1% of symptom clusters, respectively. Patients in the "all high symptom" and "high psychological disorder" classes reported significantly lower quality of life (F=40.21, p <0.05). Female gender, younger age, higher National Institutes of Health Stroke Scale scores, and lower self-efficacy and perceived social support were risk factors associated with the "high psychological disorder" class. Younger patients with lower self-efficacy and perceived social support were more likely to be in the "all high symptom" class. Conclusion: This study identified latent classes of acute stroke patients that can be used in predicting symptom-cluster experiences following a stroke. Also, the ability to characterize subgroups of patients with distinct symptom experiences helps identify high-risk patients. Focusing on symptom clusters in clinical practice can inspire us to create effective targeted interventions for subgroups of stroke patients suffering from the same symptom cluster.

Upregulated WTAP expression in colorectal cancer correlates with tumor site and differentiation.

Few reports exist regarding the expression and function of Wilms' tumor 1-associated protein (WTAP) in colorectal cancer (CRC), and the evidence is controversial. Our analysis explored the expression of WTAP in CRC tissue, and analyzed its clinical and prognostic significance. WTAP expression was significantly higher in CRC tissue than in colorectal adenoma and normal colorectal tissue. WTAP was highest in left colon tumor samples and negatively associated with tumor differentiation, as well as depth of tumor invasion. In multiple logistic regression analysis, independent predictors of WTAP expression in CRC included tumor in the left colon (odds ratio = 2.634; 95% confidence interval: 1.129-6.142; P = 0.025) and poorly differentiated tissue (0.072; 0.014-0.367; P = 0.002). No clear relationship was observed between CRC patient prognosis and WTAP expression. We suggest that WTAP expression is upregulated in CRC, highly expressed in left colon cancer and negatively correlated with tumor differentiation.

Can Goal-Based Health Management Improve the Health Knowledge, Health Belief and Health Behavior in People at High Risk of Stroke? A Non-Randomized Controlled Trial.

PURPOSE: To examine the effectiveness of goal-based health management on health knowledge, health belief and health behavior in people at high risk of stroke. PATIENTS AND METHODS: This is a two-armed and non-randomized controlled trial from May 31, 2020 to December 31, 2020. Participants were arranged to receive regular health care (n=126) or goal-based health management (n=126). The generalized estimation equation was used to analyze the changes in the participants' health knowledge, health belief and health behavior at baseline (T0), 1-month (T1), 3-month (T3), and 6-month (T6). RESULTS: A total of 243 participants completed the 6-month study, of which 123 were in the control group and 120 were in the intervention group. After receiving goal-based health management, participants' health behavior (ß=27.154, p<0.001), health knowledge (ß=10.504, p<0.001) and health belief (ß=49.057, p<0.001) scores increased significantly. CONCLUSION: Goal-based health management can effectively improve the health knowledge, health belief and health behavior of people at high risk of stroke. We recommend that nurses can provide goal-based health management for people at high risk of stroke with support from hospitals and family members of people at high risk of stroke.

Flavonoids with Potential Anti-Amyloidogenic Effects as Therapeutic Drugs for Treating Alzheimer's Disease.

Alzheimer's disease (AD) is a central neurodegenerative disease generally among the elderly; it accounts for approximately 50-75%of total cases of dementia patients and poses a serious threat to physical and mental health. Currently available treatments for AD mainly relieves its symptoms, and effective therapy is urgently needed. Deposition of amyloid-ß protein in the brain is an early and invariant neuropathological feature of AD. Currently the main efforts in developing anti-AD drugs focus on anti-amyloidogenic therapeutics that prevent amyloid-ß production or aggregation and decrease the occurrence of neurotoxic events. The results of an increasing number of studies suggest that natural extracts and phytochemicals have a positive impact on brain aging. Flavonoids belong to the broad group of polyphenols and recent data indicate a favorable effect of flavonoids on brain aging. In this review, we collect relevant discoveries from 1999 to 2021, discuss 75 flavonoids that effectively influence AD pathogenesis, and summarize their functional mechanisms in detail. The data we have reviewed show that, these flavonoids belong to various subclasses, including flavone, flavanone, biflavone, etc. Our results provide a reference for further study of the effects of flavonoids on AD and the progress of anti-AD therapy.

p-STAT3 expression in breast cancer correlates negatively with tumor size and HER2 status.

ABSTRACT: Although some studies have reported the expression and clinical significance of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in breast cancer tissues, it is still controversial whether p-STAT3 play a role in promoting or suppressing cancer. Here, we used immunohistochemistry analysis to explore expression of p-STAT3 in 407 cases of breast cancer, and analyzed the relationship between p-STAT3 expression and the clinicopathological characteristics and prognosis of breast cancer patients. Positive p-STAT3 expression was seen in 112 cases (27.5%) of breast cancer. p-STAT3 expression was negatively correlated with tumor size, tumor stage and human epidermal growth factor receptor 2 (HER2) status, and the positive rate of p-STAT3 was lowest in HER2-enriched subtype breast cancer (15.3%), while other subtypes were luminal B (23.0%), luminal A (30.2%), and triple-negative breast cancer (TNBC) (37.5%). Logistic regression model multivariate analysis showed that the independent correlation factor of p-STAT3 expression in breast cancer was tumor size (OR = 0.187, 95% CI = 0.042-0.839, P = .029) and HER2 status (OR = 0.392, 95% CI = 0.216-0.710, P = .002). In this study, no clear relationship was observed between patients' prognosis and expression of p-STAT3. Therefore, we suggest that p-STAT3 expression in breast cancer is negatively correlated with tumor size and HER2 status, but appears to have no effect on survival.

Downregulated METTL14 Expression Correlates with Breast Cancer Tumor Grade and Molecular Classification.

It is unclear whether the methyltransferase-like 14 (METTL14) protein promotes or suppresses cancer growth. We examined the association between METTL14 expression, cancer progression, and patient prognosis in a total of 398 breast cancer tissue specimens. Significantly fewer cancer tissue specimens compared with normal breast tissue expressed high levels of METTL14 (52.8% vs. 75.0%). METTL14 expression was negatively associated with tumor grade and positively associated with patient age, estrogen, and progesterone receptor status. High METTL14 expression was more common in luminal A and luminal B tissue (75.9% and 60.8%, respectively), compared with human epidermal growth factor receptor 2- (HER2-) enriched and triple-negative breast cancer (TNBC) samples (38.2% and 18.6%, respectively). In multiple logistic regression analysis, independent predictors of METTL14 expression in breast cancer included higher tumor grade (odds ratio (OR) = 0.494, 95% confidence interval (CI): 0.289-0.844; P = 0.010), TNBC subtype (OR = 0.109, 95% CI: 0.054-0.222; P < 0.001), and HER2-enriched subtype (OR = 0.298, 95% CI: 0.156-0.567; P < 0.001). No clear relationship was observed between patient prognosis and METTL14 expression. It appears that downregulated METTL14 expression in breast cancer is associated with tumor grade and molecular classification.

Impact of WNT1-inducible signaling pathway protein-1 (WISP-1) genetic polymorphisms and clinical aspects of breast cancer.

Breast cancer is the most common diagnosed malignancy in women. This study genotyped blood samples from 236 Han Chinese women with breast cancer and 128 healthy controls for single nucleotide polymorphisms (SNPs) rs2977537, rs2929970, rs2929973, rs2977530, and rs62514004, to determine whether these WNT1-inducible signaling pathway protein 1 (WISP-1) genetic polymorphisms increase the risk of developing breast cancer. Compared with wild-type (AA) carriers, those carrying the WISP1 rs62514004 AG or AG + GG genetic variants had a greater risk of developing breast cancer. In an evaluation of the association between clinicopathological aspects and the WISP1 SNP rs62514004 in the breast cancer cohort, patients with the GG genotype were less likely than those with the AA genotype to develop stage III/IV disease. Patients carrying the WISP1 rs2929973 GG + TT variant were almost twice as likely as those carrying the GT genotype to have estrogen receptor (ER)- and progesterone receptor (PR)-positive tumors, while those with the WISP1 rs62514004 AG + GG genetic variants were around twice as likely as those with the AA genotype to have HER2-positive tumors. This study details risk associations between WISP1 SNPs and breast cancer susceptibility in women of Han Chinese ethnicity.