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Background: Professional commitment of nursing students is closely related to the stability of the nursing team. Personality traits and metacognition may be related to professional commitment. We investigate the association between Big Five personality, metacognition, and professional commitment among nursing students, and further explore whether Big Five personality modifies the association between metacognition and professional commitment. Methods: From December 2023 to January 2024, a cross-sectional study was conducted among 3631 nursing students from 17 universities in China through the online platform Sojump.com by cluster sampling method and using the general information questionnaire, BFI-44 (Big Five Inventory 44) scale, metacognition scale and professional commitment scale to investigate their demographic data, personality traits, level of metacognition and level of professional commitment. Latent profile analysis was employed to identify optimal categories of personality traits. Multivariate logistic regression was used to analyze the association between the personality traits and professional commitment, as well as metacognition and professional commitment in all participants and participants with different personality traits subgroups, adjusting for potential covariates. Furthermore, the potential mediating role of metacognition between personality traits and professional commitment was also investigated. Results: Three distinct personality traits were identified: sensitive-negative personality (65.2%), ordinary personality (26.6%), and open-positive personality (8.2%). Compared with nursing students with sensitive-negative personality, nursing students with ordinary personality and open-positive personality were associated with professional commitment, respectively [OR (95% CI): 7.01 (5.99–8.20), 21.09 (15.43–28.83)]. The p value for trend of personality and professional commitment was < 0.001. Metacognition was associated with professional commitment [OR (95% CI): 5.95 (5.20–6.81); p < 0.001]. Personality traits could modify the association between metacognition and professional commitment (pinteraction = 0.009). The mediating role of metacognition between Big Five personality and professional commitment has also been verified. Conclusions: Personality traits and metacognition of nursing students need to be paid attention to, and interventions based on metacognition may help nursing students with different personality traits to improve their professional commitment level. [ABSTRACT FROM AUTHOR]

Background: Prealbumin is a symbol of protein nutrition and is involved in anti-inflammatory and neuron regeneration, but its association with the prognosis of ischemic stroke remains unclear. We aimed to prospectively explore the associations between serum prealbumin levels and adverse clinical outcomes after ischemic stroke in a large-scale cohort study. Methods: We measured serum prealbumin levels among 6609 ischemic stroke patients admitted at Minhang hospital. The primary outcome was composite of death and major disability (modified Rankin Scale [mRS] score ≥ 3) at 3 months after stroke onset, and secondary outcomes included death and the ordered 7-level categorical score of mRS. Results: During 3 months of follow-up, a total of 2118 patients developed the primary outcome. After multivariable adjustment, high prealbumin levels were associated with a decreased risk of primary outcome (odds ratio, 0.71; 95% CI, 0.59– 0.85; Ptrend< 0.0001) when 2 extreme quartiles were compared. Each unit increase of log-transformed prealbumin was associated with a 42% (95% CI, 28-53%) decreased risk of primary outcome. There was a better shift in the distribution of mRS score at 3 months with higher quartiles of serum prealbumin in ischemic stroke patients (Ptrend< 0.0001). Multivariable-adjusted spline regression model showed a linear relationship between prealbumin and the risk of primary outcome (P for linearity = 0.0036). Conclusion: High serum prealbumin level was independently associated with decreased risks of adverse clinical outcomes among ischemic stroke patients. Our findings suggested that prealbumin may be a valuable prognostic biomarker and indicated the importance of keeping nourished in the daily life. [ABSTRACT FROM AUTHOR]

Background: Impaired cardiac function was suggested to be implicated in the functional recovery after ischemic stroke, but the prognostic value of cardiac biomarkers among ischemic stroke patients remains unclear. We aimed to prospectively explore the associations of serum lactate dehydrogenase (LDH), plasma N-terminal pro-brain natriuretic peptide (NT-proBNP), and plasma high-sensitivity cardiac troponin T (hs-cTnT) with adverse clinical outcomes after ischemic stroke in a large-scale cohort study. Methods: We measured serum LDH, plasma NT-proBNP, and plasma hs-cTnT levels at baseline among 5056 ischemic stroke patients from the Minhang Stroke Cohort study. All patients were followed up at 3 months after ischemic stroke onset. The primary outcome was composite outcome of death and major disability (modified Rankin Scale [mRS] score ≥ 3) at 3 months after stroke onset, and secondary outcomes included death and ordered 7-level categorical score of the mRS. Results: During 3 months of follow-up, 1584 patients developed the primary outcome. Baseline serum LDH, plasma NT-proBNP, and plasma hs-cTnT were positively associated with the risk of adverse outcomes after ischemic stroke. The multivariable-adjusted odds ratios of primary outcome for the highest versus lowest quartile of LDH, NT-proBNP, and hs-cTnT were 1.37 (95% CI 1.13–1.66; Ptrend = 0.001), 2.51 (95% CI, 2.00–3.16; Ptrend < 0.001), and 2.24 (95% CI 1.77–2.83; Ptrend < 0.001), respectively. Each SD increase of log-transformed cardiac biomarker score was associated with a 49% (95% CI 37–62%; P < 0.001) increased risk of primary outcome. Multivariable-adjusted spline regression analyses showed linear relationships between cardiac biomarkers and the risk of primary outcome (all P for linearity < 0.001). Moreover, adding LDH, NT-proBNP, hs-cTnT, or cardiac biomarker score to conventional risk factors significantly improved the risk reclassification of primary outcome after ischemic stroke (all P < 0.05). Conclusion: High LDH, NT-proBNP, hs-cTnT, and cardiac biomarker score were independently associated with increased risks of adverse clinical outcomes among ischemic stroke patients, suggesting that cardiac biomarkers might be potential prognostic biomarkers for ischemic stroke. [ABSTRACT FROM AUTHOR]

Rheumatoid factor (RF), an established diagnostic biomarker for rheumatoid arthritis (RA), is associated with cardiovascular diseases, but its impact on clinical outcomes of ischemic stroke remains unclear. We aimed to investigate the observational associations between serum RF and prognosis of ischemic stroke, and further examined the genetic associations of RA and its therapeutic strategy, interleukin-6 (IL-6) inhibitor, with prognosis of ischemic stroke. We measured serum RF levels in 3474 Chinese ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke. The primary outcome was the composite outcome of death or major disability (modified Rankin Scale score ≥3) at 3 months after stroke onset. Mendelian randomization (MR) analyses were performed to examine the associations of genetically predicted RA and IL-6 inhibition with prognosis of ischemic stroke. During 3 months of follow-up, 866 patients (25.43%) experienced death or major disability. After multivariate adjustment, RF-positive was significantly associated with a high risk of primary outcome (OR, 1.47; 95% CI, 1.08–2.00; P =0.016) compared with RF-negative. The two-sample MR analyses suggested that genetically predicted RA was associated with an increased risk of primary outcome (OR, 1.09; 95% CI, 1.01–1.18; P=0.021), while genetically predicted IL-6 inhibition was associated with a decreased risk of primary outcome (OR, 0.88; 95% CI, 0.77–0.99; P=0.041). We found that positive RF was associated with increased risks of adverse outcomes after atherosclerotic ischemic stroke, and genetically predicted RA and IL-6 inhibition increased and decreased the risks of adverse outcomes after ischemic stroke, respectively. [ABSTRACT FROM AUTHOR]

Background: Computer gaming has recently been suggested to be associated with benefits for cognition, but its impact on incident dementia remains uncertain. We aimed to investigate the observational associations of playing computer games with incident dementia, cognitive functions, and brain structural measures, and further explore the genetic associations between computer gaming and dementia. Methods: We included 471,346 White British participants without dementia at baseline based on the UK Biobank, and followed them until November 2022. We estimated the risk of dementia using Cox proportional hazard models, and assessed the changes of cognitive functions and brain structural measures using logistic regression models and linear regression models. Mendelian randomization (MR) analyses were performed to examine the association between genetically determined computer gaming and dementia. Results: High frequency of playing computer games was associated with decreased risk of incident dementia (HR, 0.81 [95% CI: 0.69, 0.94]). Individuals with high frequency of playing computer games had better performance in prospective memory (OR, 1.46 [1.26, 1.70]), reaction time (beta, -0.195 [-0.243, -0.147]), fluid intelligence (0.334 [0.286, 0.382]), numeric memory (0.107 [0.047, 0.166]), incorrect pairs matching (-0.253 [-0.302, -0.203]), and high volume of gray matter in hippocampus (0.078 [0.023, 0.134]). Genetically determined high frequency of playing computer games was associated with a low risk of dementia (OR, 0.37 [0.15, 0.91]). Conclusions: Computer gaming was associated with a decreased risk of dementia, favorable cognitive function, and better brain structure, suggesting that computer gaming could modulate cognitive function and may be a promising target for dementia prevention. [ABSTRACT FROM AUTHOR]

Background: Social anxiety among postoperative breast cancer patients is a prevalent concern, with its intensity fluctuating throughout the course of treatment. The study aims to describe the trajectory of social anxiety in postoperative breast cancer patients, explore the influencing factors, and provide theoretical support for the construction of future intervention programs. Methods: This study was conducted from June 2022 to January 2023, encompassing 213 breast cancer patients from three first-class hospitals in China. Data collection occurred at four distinct time points. A growth mixture model was employed to identify latent categories representing the trajectories of social anxiety changes among patients. A multiple regression analysis was utilized to explore predictive factors associated with different latent trajectory categories. Results: The trajectory of social anxiety changes in postoperative breast cancer patients includes five potential categories: maintaining mild social anxiety group, changing from mild to moderate social anxiety group, maintaining moderate social anxiety group, changing from moderate to severe social anxiety group, and maintaining severe social anxiety group. Cluster analysis results indicated three types: positive, negative, and low. Logistic regression analysis revealed that younger age, spouses concerned about postoperative appearance, chemotherapy with taxol-based drugs, opting for modified radical surgery or radical mastectomy surgical approaches, and breast cancer patients with negative rumination were factors that influenced patients' social anxiety (P < 0.05). Conclusion: The trajectory of social anxiety in postoperative breast cancer patients comprises five potential categories. In clinical practice, it is essential to strengthen the management of high-risk populations susceptible to experiencing social anxiety emotions, including younger age, spouses concerned about postoperative appearance, chemotherapy with taxol-based drugs, opting for modified radical surgery or radical mastectomy surgical approaches, and breast cancer patients with negative rumination. [ABSTRACT FROM AUTHOR]

Mononuclear phagocytes (MPs) are vital components of host immune defenses against cancer. However, tumor‐infiltrating MPs often present tolerogenic and pro‐tumorigenic phenotypes via metabolic switching triggered by excessive lipid accumulation in solid tumors. Inspired by viral infection‐mediated MP modulation, here enveloped immunometabolic nanoparticles (immeNPs) are designed to co‐deliver a viral RNA analog and a fatty acid oxidation regulator for synergistic reshaping of intratumoral MPs. These immeNPs are camouflaged with cancer cell membranes for tumor homing and opsonized with anti‐CD163 antibodies for specific MP recognition and uptake. It is found that internalized immeNPs coordinate lipid metabolic reprogramming with innate immune stimulation, inducing M2‐to‐M1 macrophage repolarization and tolerogenic‐to‐immunogenic dendritic cell differentiation for cytotoxic T cell infiltration. The authors further demonstrate that the use of immeNPs confers susceptibility to anti‐PD‐1 therapy in immune checkpoint blockade‐resistant breast and ovarian tumors, and thereby provide a promising strategy to expand the potential of conventional immunotherapy. [ABSTRACT FROM AUTHOR]

Background: The homeostatic chemokines CCL19 and CCL21 are involved in carotid plaque vulnerability and post‐ischemic neuroinflammatory responses. This study aimed to examine the prognostic values of CCL19 and CCL21 in ischemic stroke. Methods: Plasma CCL19 and CCL21 were measured in 4483 ischemic stroke patients from two independent cohorts of CATIS (China Antihypertensive Trial in Acute Ischemic Stroke) and IIPAIS (Infectious Factors, Inflammatory Markers, and Prognosis of Acute Ischemic Stroke), and participants were followed up at 3 months after stroke. The primary outcome was the composite outcome of death or major disability. The associations of CCL19 and CCL21 levels with the primary outcome were examined. Results: In CATIS, multivariable‐adjusted odds ratios of the primary outcome in the highest quartiles of CCL19 and CCL21 compared with the lowest quartiles were 2.06 and 2.62, respectively. In IIPAIS, odds ratios of the primary outcome in the highest quartiles of CCL19 and CCL21 were 2.81 and 2.78 compared with the lowest quartiles, respectively. In the pooled analysis of the two cohorts, odds ratios of the primary outcome associated with the highest quartiles of CCL19 and CCL21 were 2.24 and 2.66, respectively. Similar findings were observed in the analysis with major disability, death, and the composite outcome of death or cardiovascular events as the secondary study outcomes. Adding CCL19 and CCL21 to conventional risk factors significantly improved risk reclassification and discrimination for adverse outcomes. Conclusions: Both CCL19 and CCL21 levels were independently associated with adverse outcomes within 3 months after ischemic stroke and should be further investigated for risk stratification and potential therapeutic targets of ischemic stroke. [ABSTRACT FROM AUTHOR]

Purpose: To explore the correlation between financial toxicity, social support, and social functioning in post-chemotherapy breast cancer patients, as well as any possible interaction of financial toxicity and social support on social functioning. Methods: Post-chemotherapy breast cancer patients admitted to the thyroid and breast surgery departments of three first-class general hospitals in East China from December 2020 to January 2022 were recruited by convenience sampling for a cross-sectional survey. The survey instruments included the general information form, the comprehensive scores for financial toxicity based on the patient-reported outcome measures (COST-PROM), the social roles and activity participation subscale from the patient-reported outcomes measurement system-breast-chemotherapy (PROMS-B-C) (score range: 8–40), and the social support subscale from PROMS-B-C (score range: 16–80). Results: The results showed that low social functioning (low score) in post-chemotherapy breast cancer patients was positively correlated with high financial toxicity (low score) as well as poor economic resources (low score) and poor psychosocial responses (low score) (P<0.01) and negatively correlated with low economic expenditures (low score) (P<0.01); high social functioning (high score) was positively correlated with high social support (high score) (P<0.01). The interaction analysis results showed an additive interaction between financial toxicity and social support in social functioning. Conclusion: There was an additive interaction of financial toxicity and social support in the social functioning of post-chemotherapy breast cancer patients. Those patients with high financial toxicity and low social support are the most likely to benefit from relevant intervention measures compared to other breast cancer populations. [ABSTRACT FROM AUTHOR]

Purpose: This study was designed to investigate the effectiveness and safety of massage therapy in cancer-related fatigue (CRF) and to provide a reference for the future management of CRF. Methods: Eight databases (PubMed, Embase, Cochrane Library, CINAHL, Sinomed, Chinese Scientific Journal database (VIP), Wanfang, and China National Knowledge Infrastructure (CNKI)) were systematically reviewed from inception to May 2022 for randomized controlled trials. Two reviewers critically and independently assessed the risk of bias using Cochrane Collaboration criteria and extracted correlated data using the designed form. The meta-analysis was performed using RevMan 5.3 to calculate the pooled effect sizes and 95% confidence intervals (CIs). Sensitivity analysis was performed to find the source of the heterogeneity. Publication bias was assessed via funnel plot analysis and the Egger test. Result: A total of 11 qualified studies that included 789 patients (massage therapy group: 389; control group: 400) were included in the meta-analysis. Massage therapy had a marked effect on fatigue in cancer patients [standardized mean difference (SMD) = − 1.69, 95% CI (− 2.46, − 0.93), P < 0.01], especially in breast cancer [SMD = − 1.62, 95% CI (− 2.18, − 1.05), P < 0.01]. Reflexology [SMD = − 2.71, 95% CI (− 4.65, − 0.77), P < 0.01] and Chinese massage [SMD = − 1.14, 95% CI (− 1.95, − 0.33), P < 0.01] can have a more significant effect on fatigue. Massage time is 20 to 40 min [SMD = − 2.39, 95% CI (− 4.13, − 0.66), P < 0.01], twice a week [SMD = − 3.46, 95% CI (− 5.47, − 1.45), P < 0.01] for 3–5 weeks [SMD = − 2.36, 95% CI (− 3.53, − 1.19), P < 0.01], which is more effective in relieving fatigue in cancer patients. Five studies described the occurrence of adverse events and only two studies had adverse events. Conclusion: Massage therapy can be effective in relieving fatigue in cancer patients. Current evidence suggests that reflexology is the most effective approach to relieve fatigue, particularly in the breast cancer patients. The optimal intervention frequency and cycle for massage therapy is twice a week for 3–5 weeks, and the optimal duration is 20–40 min. [ABSTRACT FROM AUTHOR]

Background: Experimental studies suggested that intercellular adhesion molecule 4 (ICAM-4) might be implicated in ischemic stroke, but the population-based evidence on the relationship between ICAM-4 and ischemic stroke were limited. Herein, we performed a two-sample Mendelian randomization (MR) analysis to investigate the associations of genetically determined plasma ICAM-4 with the risks of ischemic stroke and its subtypes. Methods: A total of 11 single-nucleotide polymorphisms associated with ICAM-4 were selected as instrumental variables based on the genome-wide association studies (GWAS) with 3,301 European individuals. Summary-level data about ischemic stroke and its subtypes were obtained from the Multi-ancestry GWAS launched by the International Stroke Genetics Consortium. We used the inverse-variance weighted method followed by a series of sensitivity analyses to evaluate the associations of genetically determined ICAM-4 with the risks of ischemic stroke and its subtypes. Results: Genetically determined higher ICAM-4 levels were significantly associated with increased risks of ischemic stroke (in the IVW method fitted to multiplicative random effects model: odds ratio [OR] per standard deviation [SD] increase, 1.04; 95% confidence interval [CI], 1.01–1.07; P = 0.006; in the IVW analysis with fixed effects model: OR per SD increase, 1.04; 95% CI, 1.01–1.07; P = 0.003) and cardioembolic stroke (in multiplicative random effects model: OR per SD increase, 1.08; 95% CI, 1.02–1.14; P = 0.004; in fixed effects model: OR per SD increase, 1.08; 95% CI, 1.03–1.13; P = 0.003). There was no association of ICAM-4 with the risks of large artery stroke and small vessel stroke. MR-Egger regression showed no directional pleiotropy for all associations, and the sensitivity analyses with different MR methods further confirmed these findings. Conclusions: We found positive associations of genetically determined plasma ICAM-4 with the risks of ischemic stroke and cardioembolic stroke. Future studies are needed to explore the detailed mechanism and investigate the targeting effect of ICAM-4 on ischemic stroke. [ABSTRACT FROM AUTHOR]

Background and Hypothesis To identify promising drug targets for psychiatric disorders, we applied Mendelian randomization (MR) design to systematically screen blood metabolome for potential mediators of psychiatric disorders and further predict target-mediated side effects. Study Design We selected 92 unique blood metabolites from 3 metabolome genome-wide association studies (GWASs) with totally 147 827 participants. Summary statistics for bipolar disorder (BIP), attention deficit hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), major depressive disorder (MDD), schizophrenia (SCZ), panic disorder (PD), autistic spectrum disorder (ASD), and anorexia nervosa (AN) originated from the Psychiatric Genomics Consortium, involving 1 143 340 participants. Mendelian randomization (MR) analyses were conducted to estimate associations of blood metabolites with psychiatric disorders. Phenome-wide MR analysis was further performed to predict side effects mediated by metabolite-targeted interventions. Results Eight metabolites were identified associated with psychiatric disorders, including five established mediators: N -acetylornithine (BIP: OR, 0.72 [95% CI, 0.66–0.79]; SCZ: OR, 0.74 [0.64–0.84]), glycine (BIP: OR, 0.62 [0.50–0.77]), docosahexaenoic acid (MDD: OR, 0.96 [0.94–0.97]), 3-Hydroxybutyrate (MDD: OR, 1.14 [1.08–1.21]), butyrylcarnitine (SCZ: OR, 1.22 [1.12–1.32]); and three novel mediators: 1-arachidonoylglycerophosphocholine (1-arachidonoyl-GPC)(BIP: OR, 0.31 [0.23–0.41]), glycoproteins (BIP: OR, 0.94 [0.92–0.97]), sphingomyelins (AN: OR, 1.12 [1.06–1.19]). Phenome-wide MR analysis showed that all identified metabolites except for N -acetylornithine and 3-Hydroxybutyrate had additional effects on nonpsychiatric diseases, while glycine, 3-Hydroxybutyrate, N -acetylornithine, and butyrylcarnitine had no adverse side effects. Conclusions This MR study identified five established and three novel mediators for psychiatric disorders. N -acetylornithine, glycine, 3-Hydroxybutyrate, and butyrylcarnitine might be promising targets against psychiatric disorders with no predicted adverse side effects. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common cancer among women with limited treatment options. To identify promising drug targets for breast cancer, we conducted a systematical Mendelian randomization (MR) study to screen blood metabolome for potential causal mediators of breast cancer and further predict target-mediated side effects. Methods: We selected 112 unique blood metabolites from 3 large-scale European ancestry-based genome-wide association studies (GWASs) with a total of 147,827 participants. Breast cancer data were obtained from a GWAS in the Breast Cancer Association Consortium (BCAC), involving 122,977 cases and 105,974 controls of European ancestry. We conducted MR analyses to systematically assess the associations of blood metabolites with breast cancer, and a phenome-wide MR analysis was further applied to ascertain the potential on-target side effects of metabolite interventions. Results: Two blood metabolites were identified as the potential causal mediators for breast cancer, including high-density lipoprotein cholesterol (HDL-C) (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.06–1.12; P = 9.67 × 10−10) and acetate (OR, 1.24; 95% CI, 1.13–1.37; P = 1.35 × 10−5). In the phenome-wide MR analysis, lowering HDL-C might have deleterious effects on the risk of the circulatory system and foreign body injury, while lowering acetate had deleterious effects on mental disorders disease. Conclusions: The present systematic MR analysis revealed that HDL-C and acetate may be the causal mediators in the risk of developing breast cancer. Side-effect profiles were characterized to help inform drug target prioritization for breast cancer prevention. HDL-C and acetate might be promising drug targets for preventing breast cancer, but they should be applied under weighting advantages and disadvantages. [ABSTRACT FROM AUTHOR]

Objective: Alzheimer's disease (AD) is the most common degenerative neurological disorder with limited therapeutic options. Therefore, it is particularly important to explore the potential biomarkers implicated in the occurrence and progression of AD prior to clinical testing.Methods: We selected 119 unique blood metabolites from 3 metabolome genome-wide association studies (GWASs) with 147,827 European participants. Summary data about AD were obtained from a GWAS meta-analysis with 63,926 European individuals from the International Genomics of Alzheimer's Project. MR analyses were performed to assess the associations of blood metabolites with AD, and a phenome-wide MR analysis was further applied to ascertain the potential on-target side effects of metabolite interventions.Results: Four metabolites were identified as causal mediators for AD, including epiandrosterone sulfate (odds ratio [OR] per SD increase: 0.60; 95% confidence interval [CI]: 0.51-0.71; p = 6.14 × 10-9 ), 5alpha-androstan-3beta-17beta-diol disulfate (OR per SD increase: 0.69; 95% CI: 0.57-0.84; p = 1.98 × 10-4 ), sphingomyelin (OR per SD increase: 2.53; 95% CI: 1.78-3.59; p = 2.10 × 10-7 ), and glutamine (OR per SD increase: 0.83; 95% CI: 0.77-0.89; p = 2.09 × 10-6 ). Phenome-wide MR analysis showed that epiandrosterone sulfate, 5alpha-androstan-3beta-17beta-diol disulfate and sphingomyelin mediated the risk of multiple diseases, and glutamine had beneficial effects on the risk of 4 diseases.Interpretation: Genetically predicted increased epiandrosterone sulfate, 5alpha-androstan-3beta-17beta-diol disulfate, and glutamine might be associated with a decreased risk of AD, while sphingomyelin was associated with an increased risk. Side-effect profiles were characterized to help inform drug target prioritization, and glutamine might be a promising target for the prevention and treatment of AD with no predicted detrimental side effects. ANN NEUROL 2022;92:756-767. [ABSTRACT FROM AUTHOR]

Objectives: Synthetic oligodeoxynucleotides (ODNs) that contain unmethylated cytosine–phosphate–guanine (CpG) motifs serve as immune adjuvants in disease treatment. However, the poor cell permeability and safety concerns limit their medical applications, and biocompatible strategies for efficient delivery of functional CpG ODNs are highly desirable. Materials and Methods: Self‐assembled, cell membrane‐coated CpG nanoparticles (NP) are prepared, and their physicochemical properties are characterized. The uncoated and membrane‐coated CpG NP are compared for their biocompatibility, cellular uptake kinetics, endocytic pathways, subcellular localization, and immunostimulatory activities in macrophages and microglia. Results: Macrophage‐ or microglia‐derived cell membrane camouflaging alters the endocytic pathways of CpG NP, promotes their targeted delivery to the cells with homologous membrane, ensures their endosomal localization, and enhances their immunomodulatory effects. Conclusions: We design a type of biomimetic NP consisting of self‐assembled CpG NP core and cell membrane shell, and demonstrate its advantages in the modulation of peripheral and central immune cells. Our study provides a new strategy for the application of CpG ODNs. [ABSTRACT FROM AUTHOR]

Background: Preclinical and epidemiological studies indicate a potential chemopreventive role of low-density lipoprotein cholesterol (LDL-C) -lowering drugs in the risks of breast cancer and prostate cancer, but the causality remains unclear. We aimed to evaluate the association of genetically proxied inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, Niemann-Pick C1-Like 1 (NPC1L1), and proprotein convertase subtilisin/kexin type 9 (PCSK9) with risks of breast cancer and prostate cancer using a two-sample Mendelian randomization (MR) method.Methods: Single-nucleotide polymorphisms (SNPs) in HMGCR, NPC1L1, and PCSK9 associated with LDL-C in a genome-wide association study (GWAS) meta-analysis from the Global Lipids Genetics Consortium (GLGC; up to 188,577 European individuals) were used to proxy inhibition of HMG-CoA reductase, NPC1L1, and PCSK9. Summary statistics with outcomes were obtained from a GWAS meta-analysis of the Breast Cancer Association Consortium (BCAC; 228,951 European females) and a Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL; 140,254 European males) consortium. SNPs were combined into multiallelic models and MR estimates representing lifelong inhibition of targets were generated using the inverse-variance weighted method.Results: Genetically proxied inhibition of HMG-CoA reductase (OR: 0.84; 95% CI 0.74-0.95; P = 0.005) and NPC1L1 (OR: 0.72; 95% CI 0.58-0.90; P = 0.005) equivalent to a 1-mmol/L (38.7 mg/dL) reduction in LDL-C was associated with reduced breast cancer risk. There were no significant associations of genetically proxied inhibition of PCSK9 with breast cancer. In contrast, genetically proxied inhibition of PCSK9 (OR: 0.81; 95% CI 0.73-0.90; P < 0.001) but not HMG-CoA reductase and NPC1L1 was negatively associated with prostate cancer. In the secondary analysis, genetically proxied inhibition of HMG-CoA reductase (OR: 0.82; 95% CI 0.71-0.95; P = 0.008) and NPC1L1 (OR: 0.66; 95% CI 0.50-0.86; P = 0.002) was associated with estrogen receptor-positive breast cancer, whereas there was no association of HMG-CoA reductase and NPC1L1 with estrogen receptor-negative breast cancer.Conclusions: Genetically proxied inhibition of HMG-CoA reductase and NPC1L1 was significantly associated with lower odds of breast cancer, while genetically proxied inhibition of PCSK9 was associated with reduced risk of prostate cancer. Further randomized controlled trials are needed to confirm the respective roles of these LDL-C-lowering drugs in breast cancer and prostate cancer. [ABSTRACT FROM AUTHOR]

: Various tools are currently available to quantify the risks of adverse clinical outcomes after an ischemic stroke. This study aimed to validate and compare prognostic scales among Chinese patients with ischemic stroke. : We compared three stroke prognostic scales (Stroke Prognostication using Age and the National Institutes of Health Stroke Scale-100 [SPAN-100], Totaled Health Risks in Vascular Events [THRIVE], and Acute Stroke Registry and Analysis of Lausanne [ASTRAL]) in 3870 Chinese patients with ischemic stroke from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The 2-year primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3). : Among all the scales, the ASTRAL score had the best accuracy for predicting 2-year prognosis in Chinese patients with ischemic stroke. The C-statistic of the ASTRAL score for the 2-year primary outcome was 0.79 (95% confidence interval [CI]: 0.78–0.80), and the Hosmer–Lemeshow goodness-of-fit test showed that the ASTRAL score fitted Chinese patients with ischemic stroke well (χ2 = 9.83, P = 0.277). The incidences of the primary outcome in the <5%, 5%–9.9%, 10%–19.9%, and ≥20% risk groups based on the ASTRAL scores were 3.93%, 7.55%, 14.29%, and 41.81%, respectively (odds ratio: 1.23; 95% CI: 1.21–1.26; P < 0.001). : The ASTRAL score had higher efficacy than the SPAN-100 and THRIVE scores in predicting 2-year adverse outcomes among Chinese patients with ischemic stroke, suggesting that it could be a valuable risk assessment tool for the 2-year prognosis of such patients. [ABSTRACT FROM AUTHOR]

Background and purpose: Elevated serum matrix metalloproteinase‐8 (MMP‐8) concentrations are associated with high risk of vascular disease, but the causality remains unclear. A two‐sample Mendelian randomization (MR) study was performed to examine the causal effect of serum MMP‐8 concentrations on the risk of ischaemic stroke, ischaemic stroke subtypes and coronary artery disease. Methods: Ten independent single‐nucleotide polymorphisms related to serum MMP‐8 concentrations were identified as instrumental variables from a genome‐wide association study of 6049 European subjects. Genetic association estimates for ischaemic stroke were obtained from the Multiancestry Genome‐wide Association Study of Stroke consortium with 446,696 European individuals. The inverse‐variance weighted method was applied to assess the causal associations of serum MMP‐8 with ischaemic stroke and its subtypes in the main analysis. Results: No significant causal association was observed for MMP‐8 levels with total ischaemic stroke, large artery stroke or cardioembolic stroke. Genetically determined 1 – unit higher log‐transformed serum MMP‐8 concentration was associated with an increased risk of small vessel stroke (odds ratio 1.25; 95% confidence interval 1.12–1.39; p < 0.001). In secondary analysis, a similar adverse impact was reported for MMP‐8 on coronary artery disease (odds ratio 1.05; 95% confidence interval 1.01–1.10; p = 0.017). Sensitivity analyses further confirmed the relationship between serum MMP‐8 level and small vessel stroke and coronary artery disease. Mendelian randomization Egger regression showed no evidence of pleiotropic bias. Conclusions: High serum MMP‐8 concentrations were causally associated with increased risks of small vessel stroke and coronary artery disease. The mechanism underlying the effect of serum MMP‐8 on the vascular system requires further investigation. [ABSTRACT FROM AUTHOR]

Objectives: Organic Selenium (Se) compounds such as L‐Se‐methylselenocysteine (L‐SeMC/SeMC) have been employed as a class of anti‐oxidant to protect normal tissues and organs from chemotherapy‐induced systemic toxicity. However, their comprehensive effects on cancer cell proliferation and tumour progression remain elusive. Materials and Methods: CCK‐8 assays were conducted to determine the viabilities of cancer cells after exposure to SeMC, chemotherapeutics or combined treatment. Intracellular reactive oxygen species (ROS) levels and lipid peroxidation levels were assessed via fluorescence staining. The efficacy of free drugs or drug‐loaded hydrogel against tumour growth was evaluated in a xenograft mouse model. Results: Among tested cancer cells and normal cells, the A549 lung adenocarcinoma cells showed higher sensitivity to SeMC exposure. In addition, combined treatments with several types of chemotherapeutics induced synergistic lethality. SeMC promoted lipid peroxidation in A549 cells and thereby increased ROS generation. Significantly, the in vivo efficacy of combination therapy was largely potentiated by hydrogel‐mediate drug delivery. Conclusions: Our study reveals the selectivity of SeMC in the inhibition of cancer cell proliferation and develops an efficient strategy for local combination therapy. [ABSTRACT FROM AUTHOR]

Background and purpose: To evaluate the association between plasma fibroblast growth factor 21 (FGF‐21) and clinical outcomes in patients with acute ischemic stroke. Methods: A total of 3412 acute ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke with plasma FGF‐21 measurements were included in this analysis. The primary outcome was a combination of death or major disability (modified Rankin Scale score ≥3) within 1 year after stroke. Results: During the 1‐year of follow‐up, 745 (21.83%) patients experienced the primary outcome; 550 had a major disability and 195 died. After multivariate adjustment, higher plasma FGF‐21 was significantly associated with increased risk of the primary outcome (odds ratio = 1.52, 95% confidence interval = 1.11–1.29). Each 1‐SD increase of log‐transformed FGF‐21 (0.67 pg/ml) was associated with 19%, 3%, and 33% increased risk of the primary outcome, major disability, and death, respectively. The addition of FGF‐21 to the conventional risk factors significantly improved prediction of the primary outcome in ischemic stroke patients (net reclassification index = 10.8%, p = 0.011; integrated discrimination improvement = 0.3%, p = 0.038). Conclusions: Higher plasma FGF‐21 was associated with poor prognosis in acute ischemic stroke patients, suggesting that FGF‐21 may be a prognostic marker for ischemic stroke. [ABSTRACT FROM AUTHOR]

Aims: Angiopoietin‐like protein 4 (ANGPTL‐4) had been reported to be associated with the risk of ischemic stroke, but its prognostic value remained unclear. The aim of this study was to investigate the association between plasma ANGPTL‐4 concentrations and prognosis of ischemic stroke. Methods: Baseline plasma ANGPTL‐4 concentrations were measured in 3379 acute ischemic stroke patients. The primary outcome was a combination of death or major disability (modified Rankin Scale score, ≥3) at 3 months after ischemic stroke. Results: At 3 months after ischemic stroke, 850 (26.16%) participants experienced major disability or died (750 major disabilities and 100 deaths). After adjusting for important covariates, odds ratios for the highest tertile of plasma ANGPTL‐4 concentrations were 1.59 (1.22–2.06) for primary outcome, 1.53 (1.18–1.97) for major disability, and 2.03 (1.03–4.00) for death when compared with the lowest tertile of plasma ANGPTL‐4 concentrations. For 1‐SD increase in log‐ANGPTL‐4 concentrations (0.44 ng/mL), the adjusted odds ratios were 1.24 (1.11–1.38), 1.14 (1.03–1.27), and 1.72 (1.32–2.23), respectively. Adding ANGPTL‐4 to a model containing conventional risk factors improved risk prediction for composite outcome of death and major disability. Conclusion: Higher plasma ANGPTL‐4 concentration was associated with poor prognosis in acute ischemic stroke patients, suggesting that ANGPTL‐4 might be a prognostic marker for ischemic stroke. [ABSTRACT FROM AUTHOR]

Recommended as a medical emergency, infectious keratitis with an acute and rapid disease progression can lead to serious damage of vision and even blindness. Herein, we present a kind of theranostic agents, which are made of vancomycin (Van)-modified fluorescent silicon nanoparticles (SiNPs-Van), enabling rapid and non-invasive diagnosis and treatment of Gram-positive bacteria-induced keratitis in a simultaneous manner. Typically, the resultant SiNPs-Van nanoagents have an ability of imaging bacteria in a short time both in vitro (5 min) and in vivo (10 min), making them an efficacious diagnostic agent for the detection of bacterial keratitis. In addition, the SiNPs-Van feature distinct antimicrobial activity, with superior activity of 92.5% at a concentration of 0.5 µg/mL against Staphylococcus aureus (S. aureus); comparatively, the antimicrobial rate of free vancomycin is 23.3% at the same concentration. We further explore the SiNPs-Van agents as eye drops for therapy of S. aureus-induced bacterial keratitis on rat model. Represented by slit-lamp scores, the keratitis severity of SiNPs-Van-treated corneas is 3.4, which is 59.6% and 77.3% slighter than vancomycin- (8.2 score) and PBS-treated corneas (15.0 score), respectively. The infected corneas recover to normal (1 score) after 7-d of SiNPs-Van treatment. Above results suggest that the SiNPs-Van could serve as a new kind of high-quality nanotheranostic agents, especially suitable for simultaneous diagnosis and therapy of Gram-positive bacteria keratitis. [ABSTRACT FROM AUTHOR]

The prognostic value of uric acid in ischemic stroke remains controversial, and it is unclear whether renal function status modifies the prognostic value of uric acid in ischemic stroke patients. A total of 3284 acute ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS) with creatinine and uric acid measurements were included in this analysis. The primary outcome was a composite of death and major disability (modified Rankin Scale score ≥3) at 1 year after stroke. The prognostic value of uric acid in ischemic stroke was appreciably modified by patients' renal function status (p for interaction <0.05). After multivariate adjustment, higher uric acid level was significantly associated with a better prognosis in patients with normal renal function (odds ratio, 0.61; 95% confidence interval, 0.45–0.83), but not in those with abnormal renal function (odds ratio, 0.87; 95% confidence interval, 0.48–1.55), when two extreme quartiles were compared. Linear association between uric acid and primary outcome was observed among patients with normal renal function (p for linearity = 0.023). The present study suggests that high serum uric acid concentration is associated with better prognosis in ischemic stroke patients with normal renal function, but not in those with abnormal renal function. The establishment of causality between increased uric acid levels and better stroke prognosis needs more suitably designed randomized clinical trials. [ABSTRACT FROM AUTHOR]

The effect of plasma endostatin on cognitive impairment after ischemic stroke remains unclear. We conducted this study to explore the association between plasma endostatin in the acute phase of ischemic stroke and post-stroke cognitive impairment (PSCI). Baseline plasma endostatin levels were measured, and cognitive function status was assessed by Montreal cognitive assessment at 3 months among 613 ischemic stroke patients. PSCI was defined as Montreal cognitive assessment score less than 26. The association of endostatin with PSCI was analyzed by logistic regression model. The receiver operating characteristic curve was applied to explore the optimal cutoff value of plasma endostatin levels in predicting PSCI. In a multivariable-adjusted model, the odds ratio for the highest vs lowest quartile of endostatin was 2.01 (95% CI, 1.15–3.53) for PSCI. Restricted cubic spline regression model showed a linear dose-response association between endostatin and PSCI (p for linearity = 0.01). The optimal cut point of endostatin was 84.22 ng/mL; higher endostatin levels (≥ 84.22 ng/mL) were associated with increased risk of 2.17-fold for PSCI (adjusted odds ratio, 2.17; 95% CI, 1.44–3.26; p = 0.0002). Furthermore, adding endostatin to a model containing conventional factors led to significant reclassification for PSCI (net reclassification improvement, 0.20; p = 0.025; integrated discrimination improvement, 0.016; p = 0.002). Our findings showed that elevated plasma endostatin levels were associated with cognitive impairment at 3 months after acute ischemic stroke, independently of established conventional risk factors, suggesting that endostatin may be an important biomarker of cognitive impairment after ischemic stroke. [ABSTRACT FROM AUTHOR]

Background: Dickkopf-3 (Dkk-3) is implicated in the progression of atherosclerosis. This study aimed to investigate the association between serum Dkk-3 and the prognosis of ischemic stroke.Methods: We measured serum Dkk-3 levels in 3344 ischemic stroke patients from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). The primary outcome was a combination of death and vascular events within 3 months after ischemic stroke.Results: During 3 months of follow-up, the cumulative incidence rates of primary outcome among ischemic stroke patients in five quintiles of serum Dkk-3 (from low to high) were 4.49%, 3.74%, 2.54%, 5.23%, and 6.73%, respectively (log-rank p = 0.004). Multivariable Cox proportional hazards regression analyses showed that compared with the third quintile of serum Dkk-3, the adjusted hazard ratios (95% confidence intervals) associated with the first and fifth quintile were 3.49 (1.46-8.34) and 4.23 (1.86-9.64) for primary outcome, 3.47 (1.06-11.36) and 5.30 (1.81-15.51) for death, and 2.66 (1.01-7.01) and 3.35 (1.33-8.40) for vascular events, respectively. Multivariable-adjusted Cox proportional hazards regression model with restricted cubic splines showed a U-shaped association between serum Dkk-3 and the risk of primary outcome (p for nonlinearity = 0.030). Moreover, adding serum Dkk-3 to conventional risk factors could improve the predictive power for primary outcome (net reclassification improvement 28.44%, p < 0.001; integrated discrimination improvement 0.48%, p = 0.001).Conclusions: Both low and high serum Dkk-3 levels are associated with increased risks of death and vascular events within 3 months after ischemic stroke, indicating that serum Dkk-3 may have a special effect on the prognosis of ischemic stroke. We also found that serum Dkk-3 might be a prognostic biomarker for ischemic stroke. Further studies are needed to replicate our findings and to determine the optimal levels of serum Dkk-3. [ABSTRACT FROM AUTHOR]

Water-dispersed silicon nanoparticles (SiNPs) are facilely prepared in an aqueous phase via microwave-assisted synthesis. The whole synthetic procedure is accomplished in a one-pot microwave reaction, without the requirement of additional surface modification. Remarkably, the resultant SiNPs feature ultrahigh fluorescence (photoluminescent quantum yield (PLQY): ∼90%), robust pH- and photo-stability, and favourable biocompatibility. [ABSTRACT FROM AUTHOR]

Fluorescent silicon (Si) nanoparticles (SiNPs) hold great promise for innumerable biological and biomedical applications owing to their unique optical properties and negligible toxicity. In this article, we present a new traditional Chinese medicine (TCM) molecule-assisted chemical synthetic strategy, suitable for the production of multifunctional small-sized (diameter: ~ 3.7 nm) SiNPs in a facile and rapid (~ 10 min) manner. Of particular significance, the resultant SiNPs simultaneously exhibited robust and stable fluorescence (photoluminescence quantum yield (PLQY): ~ 15%), as well as intrinsic anti-cancer efficacy with excellent selectivity toward cancer cells. Taking advantage of these unique merits, we further employed these novel fluorescent anti-cancer SiNPs (AC-SiNPs) for the fluorescence tracking and treatment of tumors, demonstrating long-term (~ 18 days) inhibition of tumor growth in tumor-bearing mice. Consequently, we believe this new TCM-assisted chemical synthetic method is highly attractive for designing silicon nanostructures featuring multiple functionalities, and we suggest these AC-SiNPs as novel promising tools for providing visual evidence of TCM-based cancer treatment. [ABSTRACT FROM AUTHOR]

Combination therapies for cancer have been promising strategies to reverse multidrug resistance, improve treatment efficiency, and minimize side effects. Herein, a new type of multifunctional silicon nanowire (MFSiNW)-based system, i.e., iron oxide nanoparticle and gold nanoparticle decorated silicon nanowires (IONPs@AuNPs@SiNWs), is prepared through a facile synthetic strategy. The resultant nanohybrids could load therapeutic drug molecules (e.g., doxorubicin, DOX) with high drug loading capacity (2000 mg g−1), and be simultaneously responsive to pH/NIR (near-infrared) light/magnetism, thus enabling high-efficacy synergistic treatment of drug-resistant cancer cells. The current work provides the pioneering demonstration of silicon nanomaterial-based combinational cancer treatment with high therapeutic efficiency. [ABSTRACT FROM AUTHOR]