Effects of Social Support on Medication Adherence Among Patients with Schizophrenia: Serial Multiple Mediation Model.

Purpose: This study aims to explore the serial mediating effect of stigma and depression on the association between social support and medication adherence. Patients and Methods: A cross-sectional survey was undertaken in the Changning District of Shanghai using a five-part questionnaire from August to December 2023. A convenient sampling method was employed, and 35 patients with schizophrenia were invited from each of the 9 streets in Changning District to participate in the survey, resulting in a total of 305 valid questionnaires collected. The questionnaire measured social support, stigma, depression, medication adherence, and demographic characteristics. Data analysis involved descriptive statistics, independent samples t-tests, ANOVA, Pearson correlation analysis, and the bootstrap method. Results: There was a direct and significantly positive association between social support and medication adherence (ß = 0.69, p < 0.001). Moreover, increased levels of stigma (ß = - 0.45, p = 0.013) and depression (ß = - 0.09, p = 0.017) were both associated with a decline in medication adherence. Bootstrapping analysis revealed that the association between social support and medication adherence operated indirectly through stigma (ß = 0.11, 95% CI: 0.03, 0.18). Additionally, social support was indirectly associated with medication adherence through depression (ß = 0.15, 95% CI: 0.04, 0.30). Further analysis indicated that social support had an indirect association with medication adherence through both stigma and depression (ß = 0.04, 95% CI: 0.01, 0.07). Conclusion: Stigma and depression serially mediate the association between social support and medication adherence among patients with schizophrenia. This serial multiple mediation model underscores the importance of integrating social support interventions with psychological interventions aimed at reducing stigma and depression, thereby effectively enhancing medication adherence in patients with schizophrenia.

Face-to-face Assembly Strategy of Au Nanocubes: Induced Generation of Broad Hotspot Regions for SERS-Fluorescence Dual-Signal Detection of Intracellular miRNAs.

While designing anisotropic noble metal nanoparticles (NPs) can enhance the signal intensity of Raman dyes, more sensitive surface-enhanced Raman scattering (SERS) probes can be designed by oriented self-assembly of noble metal nanomaterials into dimers or higher-order nanoclusters. In this study, we engineered a self-assembly strategy in living cells for real-time fluorescence and SERS dual-channel detection of intracellular microRNAs (miRNAs), using Mg2+-dependent 8-17E DNAzyme sequences as the driving motors, gold nanocubes (AuNCs) as the driver components, and three-branched double-stranded DNA as the linking tool. The assembly selects adenine in DNA as a reporter molecule, simplifying the labeling process of Raman reporter molecules and reducing the synthesis process. In addition, adenine is stably distributed between the faces of AuNCs and the wide hotspot region gives good reproducibility of the adenine SERS signal. In this strategy, the SERS channel was consistently stable and more sensitive compared to the fluorescence channel. Among them, the detection limit of the SERS channel was 2.1 pM and the coefficient of variation was 1.26% in the in vitro liquid phase and 1.49% in MCF-7 cells. The strategy successfully achieved accurate tracking and quantification of miRNA-21 in cancer cells, showing good reproducibility in complex samples as well as cells. The reported strategy provides ideas for exploring intracellular specific triggering of nanoparticles for precise control of self-assembly.

Comparing surgical and endoscopic resection approaches for colorectal neuroendocrine tumors within the diameter range of 10-20mm: an inverse probability weighting analysis based on the SEER database.

Background: Currently, the primary treatment modalities for colorectal neuroendocrine tumors (CRNET) with a diameter between 10mm and 20mm are surgical resection (SR) and endoscopic resection (ER). However, it remains unclear which surgical approach yields the greatest survival benefit for patients. Methods: This study included data from patients diagnosed with CRNET with tumor diameters ranging from 10mm to 20mm between the years 2004 and 2019, obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Patients were categorized into ER and SR groups based on the respective surgical approaches. Inverse probability weighting (IPTW) was employed to mitigate selection bias. Kaplan-Meier analysis and log-rank tests were utilized to estimate overall survival (OS) and cancer-specific survival (CSS). Cox regression analysis (univariate and multivariate) was performed to evaluate potential factors influencing survival. Results: A total of 292 CRNET patients were included in this study (ER group: 108 individuals, SR group: 184 individuals). Prior to IPTW adjustment, Kaplan-Meier analysis and Cox proportional hazard regression analysis demonstrated that the OS and CSS of the SR group were inferior to those of the ER group. However, after IPTW adjustment, no statistically significant differences in prognosis were observed between the two groups. Subgroup analyses revealed that patients with muscular invasion, positive lymph nodes, or distant metastasis derived greater survival benefits from SR. Significant differences in OS and CSS between the two groups were also observed across different age groups. Conclusion: For patients with mucosal-limited lesions and without local lymph node or distant metastasis, ER is the preferred surgical approach. However, for patients with muscular invasion or positive lymph nodes/distant metastasis, SR offers a better prognosis. The choice of surgical approach should be based on the specific clinical characteristics of patients within different subgroups.

An ultrasound-based nomogram for predicting axillary node pathologic complete response after neoadjuvant chemotherapy in breast cancer: Modeling and external validation.

INTRODUCTION: The staging and treatment of axillary nodes in breast cancer have become a focus of research. For breast cancer patients with fine-needle aspiration-or core needle biopsy-confirmed positive nodes, axillary lymph node dissection (ALND) after neoadjuvant chemotherapy (NAC) is still a standard treatment. However, some patients achieve an axillary pathologic complete response (pCR) after NAC. In this study, the authors sought to construct a model to predict axillary pCR in patients with positive axillary lymph nodes (cN+) breast cancer. METHODS: Data from patients with pathologically proven cN+ breast cancer treated with NAC followed by ALND between January 2010 and April 2019 at the Peking University Cancer Hospital were reviewed. Axillary lymph node status was assessed using ultrasonography before and after NAC. The patient cohort was assigned to the construction and internal validation cohorts according to admission time. A nomogram was constructed based on the significant factors associated with axillary pCR. The predictive performance of the model was externally validated using data from Peking University First Hospital. RESULTS: This study included 953 and 267 patients from Peking University Cancer Hospital and Peking University First Hospital, respectively. In the construction cohort, 39.7% (238 of 600) of patients achieved axillary pCR after NAC. The result of multivariate logistic regression analysis showed that tumor grade, clinical nodal response, NAC regimen, tumor pCR, lymphovascular invasion, and tumor biologic subtype were significant independent predictors of ypN0 (p < 0.05). The areas under the receiver operating characteristic curves for the construction, validation, and independent testing cohorts were 0.87 (95% confidence interval [CI], 0.84-0.90), 0.83 (95% CI, 0.79-0.87), and 0.84 (0.79-0.89), respectively. CONCLUSIONS: A nomogram was constructed to predict the pCR of axillary lymph nodes after NAC for breast cancer. Validation of both the internal and external cohorts achieved good predictive performance, indicating that the model has preliminary clinical application prospects.

Synovial sarcoma of the viscera (lung and jejunum): a case report.

We report the case of a woman nearing 70 years old who was admitted to the hospital with a complaint of "epigastric distension for 1 month". Her main signs and symptoms were progressive abdominal distension and occasional abdominal pain. Computed tomography suggested an abdominal mass. She had a surgical history of synovial sarcoma (SS) of the lungs. After admission, she was diagnosed with jejunal SS following a puncture biopsy and laparoscopic surgery. This disease usually occurs in the soft tissues of the limbs, and it is extremely rare for SS to originate in the jejunum. The morphologic heterogeneity of SS overlaps with other tumors and makes the diagnosis particularly difficult. Imaging studies usually lack specificity; however, measuring multiple immunohistochemical markers can greatly assist in the diagnosis and differential diagnosis of SS. This case not only enriches our understanding of SS and describes a rare site of origin, but also emphasizes the importance and challenges of achieving an accurate diagnosis. Immunohistochemical and molecular biological testing have important roles in the definitive diagnosis, highlighting the need for precise and innovative diagnostic and therapeutic approaches in SS.

Identification and clinical validation of the role of anoikis-related genes in diabetic foot.

This study aims to investigate the role of anoikis-related genes in diabetic foot (DF) by utilizing bioinformatics analysis to identify key genes associated with anoikis in DF. We selected the GEO datasets GSE7014, GSE80178 and GSE68183 for the extraction and analysis of differentially expressed anoikis-related genes (DE-ARGs). GO analysis and KEGG analysis indicated that DE-ARGs in DF were primarily enriched in apoptosis, positive regulation of MAPK cascade, anoikis, focal adhesion and the PI3K-Akt signalling pathway. Based on the LASSO and SVM-RFE algorithms, we identified six characteristic genes. ROC curve analysis revealed that these six characteristic genes had an area under the curve (AUC) greater than 0.7, indicating good diagnostic efficacy. Expression analysis in the validation set revealed downregulation of CALR in DF, consistent with the training set results. GSEA results demonstrated that CALR was mainly enriched in blood vessel morphogenesis, endothelial cell migration, ECM-receptor interaction and focal adhesion. The HPA database revealed that CALR was moderately enriched in endothelial cells, and CALR was found to interact with 63 protein-coding genes. Functional analysis with DAVID suggested that CALR and associated genes were enriched in the phagosome component. CALR shows promise as a potential marker for the development and treatment of DF.

Prognostic implications of T stage in different pathological types of colorectal cancer: an observational study using SEER population-based data.

OBJECTIVES: Colorectal cancer (CRC) encompasses a spectrum of pathological types, each exhibiting distinct biological behaviours that challenge the conventional T-staging system's predictive efficiency. Thus, this study aims to explore the prognostic significance of the T stage across various CRC pathological types, seeking to unravel insights that could enhance prognostic assessment in this complex disease. STUDY DESIGN: We performed a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database for primary CRC cases from 2010 to 2017. SETTING: The SEER database, comprising data from various US regional and state cancer registries, identified 39 321 patients with CRC. Our analysis focused on the three most common CRC pathological types: adenocarcinoma (AC), mucinous adenocarcinoma (MC) and signet ring cell carcinoma (SR). PRIMARY OUTCOME MEASURES: The study used Cox regression models to evaluate how different pathological characteristics impact mortality risk in patients with CRC. Time-dependent receiver operating characteristic curves were also applied to assess the prognostic accuracy of various tumour node metastasis (TNM)/non-mucinous (NM) stages. RESULTS: We observed significant associations between T stage and mortality risk for patients with AC and MC. Notably, in comparison to those at T1 stage, patients with AC in the T4 stage demonstrated a 2.01-fold increase in mortality risk (HR=2.01, 95% CI: 1.89 to 2.15), while patients with MC at T4 stage showed a 1.42-fold increase (HR=1.42, 95% CI: 1.03 to 1.97). However, within the SR group, T stages did not independently impact survival, showing no significant distinction (HR=1.07, 95% CI: 0.59 to 1.95). Intriguingly, the traditional TNM staging systems demonstrated limited discriminatory power in predicting prognosis for patients with SR when compared with the more innovative NM staging systems. CONCLUSIONS: This study uncovers important insights about the prognostic significance of the T stage in different types of CRC, highlighting the need for personalised assessments based on specific histological subtypes.

The effect of perceived social support and health literacy on parental COVID-19 vaccine hesitation in preschool children: a cross-sectional study.

Children are generally susceptible to COVID-19, and infection with COVID-19 may cause serious harm to children. COVID-19 vaccination is an effective way to prevent infection at present, and many factors affect children's COVID-19 vaccination. This study aimed to explore the effects of perceived social support and health literacy on hesitancy towards first and second vaccine dose. This cross-sectional study was conducted in the Minhang District of Shanghai, China, in October 2022. A total of 1150 parents of preschool children from 10 kindergartens participated. The survey encompassed four sections, capturing data on sociodemographic attributes, health literacy, perceived social support, and parental COVID-19 vaccine hesitancy. Health literacy was measured using a self-designed questionnaire consisting of four dimensions. Perceived social support was assessed using the MSPSS questionnaire. Hierarchical multiple logistic regression was used to examine the relationship between the independent variables and parental hesitancy towards the first and second doses of COVID-19 vaccine. Parental hesitancy rate for the first dose of the COVID-19 vaccine was 69.6%, and for the second dose, it was 33.1%. The final integrated model showed that parental hesitancy towards the first and the second dose of COVID-19 vaccine was associated with parental educational level, allergy in children, information decision-making and information comprehension ability, perceived social support from family and friends. Health literacy and perceived social support are influence factors for parental hesitancy towards COVID-19 vaccine for preschool children. The findings will provide insights for future intervention studies on COVID-19 vaccine hesitancy and inform the development of vaccination policies.

Roles of AFAP1-AS1 in Gynecology and Urogenital System.

BACKGROUND: Human disease onset and progression are strongly associated with aberrant long noncoding RNA (lncRNA) expression, highlighting the functional regulatory role of lncRNA. Actin filament-associated protein 1-antisense RNA 1 (AFAP1-AS1), a member of lncRNAs, is located on the antisense strand of Actin filament-associated protein 1 (AFAP1). METHODS: We conducted a comprehensive review of AFAP1-AS1's functions in gynecology and urogenital systems using the "PubMed" database. RESULTS: Our analysis reveals that AFAP1-AS1 is overexpressed and engages in the initiation and process of gynecological and urogenital diseases. The regulatory mechanisms employed by AFAP1-AS1 involve four major strategies: gene-level effects, competition for microRNA (miRNA) repression, protein binding, participation in signaling networks that influence cellular processes such as proliferative phenotype, migration, invasiveness, epithelial-mesenchymal transition (EMT), cycle regulation, drug resistance, and more. Furthermore, AFAP1-AS1 is implicated in guiding clinicopathological characteristics. CONCLUSION: AFAP1-AS1 holds promise as a potent diagnostics and treatment option for gynecological and genitourinary systems in the future.

IRF4 induces M1 macrophage polarization and aggravates ulcerative colitis progression by the Bcl6-dependent STAT3 pathway.

Ulcerative colitis (UC) is an idiopathic chronic intestinal inflammation. An increasing body of evidence shows that macrophages play an important role in the pathogenesis of UC. Interferon regulatory factor 4 (IRF4) is crucial for the development of autoimmune diseases via regulating immune cells. This research was designed to explore the function of IRF4 in UC and its association with macrophage polarization. The in vitro model of UC was established by stimulating colonic epithelial cells with tumor necrosis factor α (TNF-α). A mouse model of UC was constructed by injecting C57BL/6 mice with dextran sulfate sodium salt. Flow cytometry was used to assess percentage of CD11b+ CD86+ and CD11b+ CD206+ cells in bone marrow macrophages. Occult blood tests were used to detect hematochezia. Hematoxylin and eosin staining assay was used to assess colon pathological changes. Enzyme-linked immunosorbent assay (ELISA) was used to detect concentrations of inflammatory cytokines. The interaction of IRF4 and B-cell lymphoma 6 (Bcl6) was confirmed using GST pull-down and coimmunoprecipitation assays. Our findings revealed that IRF4 promoted cell apoptosis and stimulated M1 macrophage polarization in vitro. Furthermore, IRF4 aggravated symptoms of the mouse model of UC and aggravated M1 macrophage polarization in vivo. IRF4 negatively regulated Bcl6 expression. Downregulation of Bcl6 promoted apoptosis and M1 macrophage polarization in the presence of IRF4 in vitro and in vivo. Moreover, Bcl6 positively mediated the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. In conclusion, IRF4 aggravated UC progression through promoting M1 macrophage polarization via Bcl6/JAK2/STAT3 pathway. These findings suggested that IRF4 might be a good target to competitively inhibit or to treat with UC.

CYP1B1-AS1 Delays the Malignant Progression of Colorectal Cancer by Binding with NOP58.

BACKGROUND: Colorectal cancer (CRC) is a prevalent type of gastrointestinal cancer, and its poor prognosis is mainly attributed to the occurrence of invasion and metastasis. CYP1B1-AS1, as non-coding RNA, plays an important role in tumorigenesis and progression. However, the mechanism by which CYP1B1-AS1 acts in CRC is not yet understood. AIMS: The objective of this study was to investigate how CYP1B1-AS1 contributes to the development of CRC, and provide a base for CRC diagnosis and treatment. METHODS: RT-qPCR was used to detect the expression level of CYP1B1-AS1 in CRC and adjacent tissues. CCK-8, Edu, scratch healing, and transwell experiments were used to detect the changes of proliferation, migration, and invasion ability of CRC cells after overexpression or knockdown of CYP1B1-AS1 respectively. The RNA binding protein NOP58 combined with CYP1B1-AS1 was verified by RIP and RNA Pull-down experiments. Functional recovery experiments validated the interaction between CYP1B1-AS1 and NOP58 in CRC cells. The changes of EMT-related proteins were detected by Western blot, and the half-life of transcription factor SNAIL mRNA were detected by RT-qPCR after overexpression or knockdown of NOP58. RESULTS: CYP1B1-AS1 was found to be significantly downregulated in CRC compared to adjacent noncancerous tissues. Experiments conducted in vitro and in vivo confirmed that upregulation of CYP1B1-AS1 significantly inhibited the proliferation, migration, and invasion of CRC cells. In addition, CYP1B1-AS1 can directly bind to NOP58 and negatively regulate NOP58. The effect of overexpression CYP1B1-AS1 was reversed by NOP58 overexpression. NOP58 regulates the EMT process of CRC cells by affecting the stability of EMT-related transcription factor SNAIL mRNA, and then affects the progress of CRC. CONCLUSION: This research proves that CYP1B1-AS1 can inhibit the occurrence of EMT in CRC by binding with NOP58, thus delaying the progress of CRC. This finding indicates that CYP1B1-AS1 may be a novel biomarker to improve the diagnosis and treatment of CRC.

Fully Endoscopic Microvascular Decompression for Trigeminal Neuralgia Caused by Vertebrobasilar Artery: A Case Series Review: 2-Dimensional Operative Video.

BACKGROUND AND OBJECTIVE: Microvascular decompression (MVD) is the most definitive and preferred surgical treatment for trigeminal neuralgia (TN). Treatment of TN caused by the vertebrobasilar artery (VBA) has been reported to be challenging and less satisfactory in complications and recurrence. Endoscopy has been implemented to provide a comprehensive view of neurovascular conflicts and minimize brain tissue stretch injury while exploring the trigeminal nerve. However, there are few retrospective studies on the treatment of TN caused by VBA by fully endoscopic microvascular decompression (E-MVD). This article aimed to illustrate the safety and efficacy of E-MVD for TN caused by the VBA. METHODS: Clinical data for 26 patients with TN caused by the VBA who underwent E-MVD from 2019 to 2022 were retrospectively analyzed. The characteristics of vertebrobasilar-associated TN were summarized. The safety and efficacy of E-MVD for vertebrobasilar-associated TN were estimated based on the analysis of intraoperative manipulation, postoperative symptom relief, and complications. RESULTS: Intraoperatively, the vertebrobasilar artery was regarded as a direct offending vessel in all 26 patients with TN, the vertebral artery in 18 (69.23%) and the basilar artery in 10 (38.46%). In addition to the vertebrobasilar artery, other vessels involved included the superior cerebellar artery in 12 patients, anterior inferior cerebellar artery in 9, posterior inferior cerebellar artery in 1, and veins in 4. All patients underwent E-MVD, and TN was entirely resolved in 26 (100%) patients immediately postoperatively. During the follow-up period of 12-45 months, no recurrence or serious complications were found. There were no serious postoperative complications, such as cerebellar swelling, intracranial hemorrhage, or death. CONCLUSION: E-MVD for vertebrobasilar-associated TN is effective and safe.

Fully neuroendoscopic resection of cerebellopontine angle tumors through a retrosigmoid approach: a retrospective single-center study.

The objective of this study is to preliminarily investigate the surgical safety, efficacy, techniques, and clinical value of fully neuroendoscopic surgery for the resection of cerebellopontine angle (CPA) tumors via a retrosigmoid approach. The clinical data of 47 cerebellopontine angle area (CPA) tumors that were treated by full neuroendoscopic surgery from June 2014 to June 2023 were retrospectively analyzed. The efficacy and advantages of the surgical techniques were evaluated based on indicators such as duration of the surgery, neuroendoscopic techniques, intraoperative integrity of nerves and blood vessels, extent of tumor resection, outcomes or postoperative symptoms, and incidence of complications. The 47 cases of cerebellopontine angle tumors include 34 cases of epidermoid cysts, 7 cases of vestibular schwannomas, and 6 cases of meningiomas. All patients underwent fully neuroendoscopic surgery. Twenty tumors were removed using the one-surgeon two-hands technique, and 27 tumors were removed using the two-surgeons four-hands technique. The anatomical integrity of the affected cranial nerves was preserved in all 47 cases. None of the patients suffered a postoperative hemorrhage, cerebrospinal fluid leak, and aseptic or septic meningitis, or died. The rate of total tumor resection was 72.3% (34/47), and the symptom improvement rate was 89.4% (42/47). All patients were followed up for 2 to 12 months, and none died nor showed any signs of tumor recurrence. By analyzing 47 fully neuroendoscopic resections of CPA tumors using the posterior sigmoid sinus approach in our center, we believe that such method allows complete, safe, and effective resection of CPA tumors and is thereby worthy of clinical promotion.

New animal model of chronic gout reproduces pathological features of the disease in humans.

OBJECTIVES: Gout, as the most prevalent form of inflammatory arthritis, necessitates the use of animal models to investigate the molecular mechanisms involved in its development. Therefore, our objective was to develop a novel chronic mouse model of gout that more closely mimics the progression of gout in humans. METHODS: A novel chronic mouse model of gout was established by a simple method, which does not require high technical proficiency, predominantly involves daily intraperitoneal injections of potassium oxonate for approximately 4 months, combined with a high fat-diet and injections of acetic acid into the hind paws to facilitate the formation of monosodium urate (MSU). Arthritis scores and paw oedema were assessed, behavioural tests were conducted, and histopathological and imaging evaluations of the arthritic paw joints were performed. RESULTS: After 4 months of induction, mice in the model group exhibited noticeable increases in arthritis severity, joint and cartilage damage, as well as bone erosion. Gomori's methenamine silver stain revealed the presence of MSU crystal deposition or tophi in the paw joints or ankle joints of up to 37.9% of the model mice (11 out of 29 mice). Moreover, treatment with benzbromarone effectively prevented the further development of gout or tophi formation in model mice. CONCLUSIONS: Our model more accurately replicates the pathological features of gouty arthritis compared with gout induced by MSU crystal injections. Therefore, it is particularly suitable for further investigations into the pathogenesis of gout and also serves as a valuable platform for screening potential antigout agents.

Endovascular treatment of multiple intracranial aneurysms.

Multiple intracranial aneurysms are difficult to treat. In order to investigate the effect and safety of endovascular treatment for multiple intracranial aneurysms, 54 consecutive patients with 116 multiple intracranial aneurysms treated with endovascular embolization were retrospectively enrolled. Angiography was performed immediately after embolization and at each follow-up. All clinical data were analyzed. Of the 116 aneurysms, 56 (48.3%) were embolized with coiling alone, 19 (16.4%) with stent-assisted coiling, 31 (26.7%) with stenting alone, and 10 (8.6%) with flow diverters plus coiling. After embolization, 31 (27.6%) aneurysms with stenting alone had no apparent change in size, and in the remaining 84 aneurysms, complete occlusion was achieved in 50 aneurysms (59.5%), near-complete occlusion in 26 (31.0%), and incomplete occlusion in 8 (9.5%). Thrombus formation at the aneurysm neck occurred in 3 patients (5.6%), coil protrusion in 2 (3.7%), and intraprocedural rupture in 1 (1.9%), resulting in a total complication rate of 11.1%. Follow-up angiography was performed in 44 (81.5%) patients 6 to 90 months (mean 49) later. Among 50 completely occluded aneurysms, 38 (76%) aneurysms remained completely occluded, and 4 (8%) aneurysms recurred. Among 26 aneurysms with initial near-complete occlusion, 12 (46.2%) aneurysms with neck remnant had progressive thrombosis to complete occlusion, 2 (7.7%) had no change compared with immediate occlusion, and 5 (19.2%) regrew. In conclusion, endovascular embolization with intracranial stenting and coiling is safe and effective and may play an increasingly important role in the management of multiple intracranial aneurysms.

[Eriodictyol improves cognitive function in 5×FAD mice of Alzheimer's disease by inhibiting the microglia NLRP3 inflammasome signaling pathway].

Objective To investigate the therapeutic effects of eriodictyol on transgenic mice with five familial Alzheimer's disease (5×FAD) and the modulation of NOD-like receptor-pyrin domain containing 3 (NLRP3) inflammasome in microglia. Methods The 8-month-old 5×FAD mice were randomly divided into AD model group and eriodictyol-treated AD group. Same-aged wild-type C57BL/6J mice were randomly divided into wild-type (WT) control group and eriodictyol-treated WT group. Morris water maze and Y-maze experiments were performed to assess the cognitive function of each group of mice. Immunofluorescence histochemical staining was performed to detect the expression of NLRP3, caspase-1 and interleukin 18 (IL-18) in mouse brain tissue, and Western blot was performed to detect the protein levels of NLRP3, apoptosis-associated speckle-like protein containing a CARD (ASC), caspase-1, IL-18, IL-1ß and ion calcium-binding adaptor molecule 1 (Iba-1) in mouse brain tissue. Results Compared with the WT group and the eriodictyol-treated WT group, cognitive function was significantly impaired in the AD group mice, and the expression of NLRP3, caspase-1, IL-18, ASC, IL-1ß and Iba1 were increased in microglia of mouse brain tissue. After eriodictyol treatment, learning memory and cognitive function were improved, and the expression of NLRP3, ASC, caspase-1, IL-1ß, IL-18 and Iba1 were all down-regulated in the eriodictyol-treated AD group mice compared with the AD group mice. Conclusion Eriodictyol may improve cognitive function in animal models of AD by inhibiting the activation of the NLRP3 signaling pathway in microglia.

Parents' intention to vaccinate their preschool children against COVID-19: Combining the health belief model and the theory of planned behavior.

The vaccination rate of COVID-19 in preschool children is low, and parents' intention to vaccinate their children is also low due to multiple factors. This study aimed to establish an integrated model based on the Health Belief Model (HBM)and Theory of Planned Behavior (TPB), to explore the factors influencing parents' intention to vaccinate their preschool children with the first and second doses of COVID-19 vaccines. A total of 1264 parents of preschool children from 10 kindergartens participated in this study. Hierarchical multiple logistic regression was used to analyze the intention separately. For the integrated model with the first dose of vaccine of COVID-19, introducing the HBM variable in model 1 explained 33.98% of the variance (F = 398.71, p < .001), then upon adding the TPB variable in model 2, the explanation of variance increased to 41.93% (F = 491.94, p < .001) and parents' intention were associated with their perceived barriers, cues to action, and subjective norms. For the integrated model with the second dose of vaccine of COVID-19, introducing the HBM variable in Model 1 explained 23.76% of the variance (F = 68.82, p < .001), then upon adding the TPB variable in model 2, the explanation of variance increased to 26.67% (F = 77.24, p < .001), and parents' intention was associated with cues to action and subjective norms. The combination of the two theories improves the explanatory power of parents' intention to vaccinate their preschool children against COVID-19, and provides a basis for the development of effective interventions for vaccination of COVID-19 for preschool children.

Greater hemodynamic stresses initiate aneurysms on major cerebral arterial bifurcations.

Objective: To retrospectively investigate the hemodynamic stresses in initiating aneurysm formation on major cerebral arterial bifurcations with computational fluid dynamics (CFD) analysis. Methods: The cerebral 3D angiographic data of major cerebral arterial bifurcations of the internal carotid, middle cerebral, anterior cerebral, and basilar arteries in 80 patients harboring bifurcation aneurysms and 80 control subjects with no aneurysms were retrospectively collected for the CFD analysis of hemodynamic stresses associated with aneurysm formation. Results: Bifurcation angles at major bifurcations in all patients were significantly positively (P < 0.001) correlated with the age. At the center of direct flow impingement (CDFI) on the bifurcation wall, total pressure was the highest but dropped rapidly toward the branches. Wall shear stress, dynamic pressure, strain rate, and vorticity were lowest at the CDFI but they increased quickly toward the branches. The bifurcation angle was significantly (P < 0.001) enlarged in patients with bifurcation aneurysms than those without them, for all major arterial bifurcations. Most aneurysms leaned toward the smaller arterial branch or the arterial branch that formed a smaller angle with the parent artery, where the hemodynamic stresses increased significantly (P < 0.05), compared with those on the contralateral arterial branch forming a larger angle with the parent artery. Following the aneurysm development, all the hemodynamic stresses on the aneurysm dome decreased significantly (P < 0.001) compared with those at the initiation site on the bifurcation wall after virtual aneurysm removal. With the decrease of bifurcation angles, all the hemodynamic stresses decreased. Conclusion: The formation of intracranial aneurysms on major intracranial arterial bifurcations is significantly associated with locally abnormally augmented hemodynamic stresses, which must be reduced.

The effect of anxiety, depression, and structural social capital on life satisfaction among people with hearing disabilities: a cross-sectional study in Shanghai, China.

Background: Life satisfaction (LS) serves as a crucial indicator of social wellbeing and plays a significant role in formulating strategies aimed at enhancing health outcomes among the hearing-disabled population. This study aimed to examine the effect of anxiety, depression, and structural social capital on life satisfaction among people with hearing disabilities in Shanghai, China. Methods: A cross-sectional study was conducted in Shanghai, China. As of March 2022, 337 people with hearing disabilities were recruited from the Shanghai Disabled Persons' Federation. An online survey was conducted using a four-part questionnaire to collect data including demographic characteristics, the Hospital Anxiety and Depression Scale (HADS), the Social Capital Scale (SCS), and a single-item question to measure life satisfaction. One-sample t-tests, Pearson's correlation analysis, and hierarchical multiple regression analysis were performed. Results: Anxiety (ß = - 0.153) and depression (ß = - 0.242) were significant factors influencing life satisfaction among people with hearing disabilities. Structural social capital also played an influential role in life satisfaction, and people with hearing disabilities who lack social networks (ß = 0.125) and social support (ß = 0.121) reported significantly lower levels of life satisfaction. However, no significant relationship was found in this study between LS and other components of structural social capital, such as social participation. Conclusion: This study shows that paying attention to mental health is critical for people with hearing disabilities to achieve social wellbeing and promote LS improvement. At the same time, the government and society also need to focus on the structural social capital, provide various social service programs, enhance social support, and expand social networks, improving LS for people with hearing disabilities.

Inhibition of extracellular vesicle-derived miR-146a-5p decreases progression of melanoma brain metastasis via Notch pathway dysregulation in astrocytes.

Melanoma has the highest propensity of all cancers to metastasize to the brain with a large percentage of late-stage patients developing metastases in the central nervous system (CNS). It is well known that metastasis establishment, cell survival, and progression are affected by tumour-host cell interactions where changes in the host cellular compartments likely play an important role. In this context, miRNAs transferred by tumour derived extracellular vesicles (EVs) have previously been shown to create a favourable tumour microenvironment. Here, we show that miR-146a-5p is highly expressed in human melanoma brain metastasis (MBM) EVs, both in MBM cell lines as well as in biopsies, thereby modulating the brain metastatic niche. Mechanistically, miR-146a-5p was transferred to astrocytes via EV delivery and inhibited NUMB in the Notch signalling pathway. This resulted in activation of tumour-promoting cytokines (IL-6, IL-8, MCP-1 and CXCL1). Brain metastases were significantly reduced following miR-146a-5p knockdown. Corroborating these findings, miR-146a-5p inhibition led to a reduction of IL-6, IL-8, MCP-1 and CXCL1 in astrocytes. Following molecular docking analysis, deserpidine was identified as a functional miR-146a-5p inhibitor, both in vitro and in vivo. Our results highlight the pro-metastatic function of miR-146a-5p in EVs and identifies deserpidine for targeted adjuvant treatment.