Alzheimer's disease (AD) is a common neurodegenerative disorder among the elderly, and BuChE has emerged as a potential therapeutic target. In this study, we reported the development of compound 8e, a selective reversible BuChE inhibitor (eqBuChE IC₅₀ = 0.049 μmol/L, huBuChE IC₅₀ = 0.066 μmol/L), identified through extensive virtual screening and lead optimization. Compound 8e demonstrated favorable blood-brain barrier permeability, good drug-likeness property and pronounced neuroprotective efficacy. Additionally, 8e exhibited significant therapeutic effects in zebrafish AD models and scopolamine-induced cognitive impairments in mice. Further, 8e significantly improved cognitive function in APP/PS1 transgenic mice. Proteomics analysis demonstrated that 8e markedly elevated the expression levels of very low-density lipoprotein receptor (VLDLR), offering valuable insights into its potential modulation of the Reelin-mediated signaling pathway. Thus, compound 8e emerges as a novel and potent BuChE inhibitor for the treatment of AD, with significant implications for further exploration into its mechanisms of action and therapeutic applications.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Objective: To explore the relationship between the parent-child relationship perceived by parents and students of junior high school and students internalization problems, so as to provide a pathway for the prevention and control of students internalization problems. Methods: In June 2023, a convenience cluster sampling method and a matching method between students and their fathers/mothers were used to select 965 pairs of students and their fathers (or mothers) from three junior high schools in Guizhou Province, and the Middle School Student s Parent-Child Relationship Questionnaire (parent and student edition) and the Strengths and Difficulties Questionnaire (student edition) were used to measure the perception of parent-child relationship by parents and students and the internalization problems of students. The response surface analysis method was used to analyze the relationships between parents and students perceptions of parent-child relationship and students internalization problems. Results: The comparison of standardized scores revealed that 58.44% of parents and junior high school students had different perceptions of parent-child relationship. After controlling for students gender, students grade, and parents education level, the results showed that when the parent-child relationship perceived by parents and students was congruent, the students internalization problems increased with the decrease of parent-child relationship level ( a 1=-0.43, 95%CI=-0.62 to -0.25, P <0.05). When the parent-child relationship perceived by parents and students was incongruent, and the parent-child relationship perceived by parents was higher than that of students, students internalization problems were more ( a 3=-0.36, 95%CI=-0.51 to -0.19, P <0.05). Conclusions Students internalization problems are closely related to perceptions of parent-child relationship. Improving the quality of the parent-child relationship and paying attention to the differences in perception of the parent-child relationship are helpful for evaluating and intervening in the internalization problems of junior high school students.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.

Objective:To develop an imaging-assisted diagnostic tool for schizophrenia based on multimodal magnetic resonance imaging and artificial intelligence techniques.Methods:Three independent datasets were utilized. For each subject, four brain structural metrics including grey matter volume (GMV), white matter volume (WMV), cortical thickness (CT) and deformation-based morphometry (DBM) indicators were extracted from the structural magnetic resonance imaging (sMRI) data, and three brain functional metrics including amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo) and functional connectivity (FC) were extracted from the functional magnetic resonance imaging (fMRI) data. To distinguish patients with schizophrenia and healthy controls, single-metric classification models and multi-metrics-fusion classification models were trained and tested using a within-dataset and a between-dataset cross-validation strategy.Results:The results of within-dataset cross-validation showed that the highest accuracy of the single-metric classifications for schizophrenia diagnosis was 86.18% (FC), while the multi-metric-fusion classifications could reach an accuracy of 90.21%. The results of between-datasets cross-validation showed that the highest accuracy of the single-metric classifications for schizophrenia diagnosis was 69.02% (ReHo), while the multi-metric-fusion classifications could reach an accuracy of 71.25%.Conclusion:The functional metrics generally outperforms the structural metrics for the classification between patients with schizophrenia and heathy controls. Additionally, fusion of multi-modal brain imaging metrics can improve the classification performance. Specifically, the fusion of CT, DBM, WMV, FC and ReHo demonstrates the highest classification accuracy, which is a potential tool for imaging-assisted diagnosis of schizophrenia.

Objective:To explore the current status and influencing factors of self-management in colorectal cancer patients with stoma.Methods:From June to September 2022, a total of 390 colorectal cancer patients with stoma at a Class Ⅲ Grade A hospital in Tianjin were selected as study subjects using convenience sampling method, and were investigated by General Information Questionnaire, Enterostomy Self-Management Questionnaire, Connor-Davidson Resilience Scale, and Acceptance of Disability Scale. Pearson correlation analysis was used to investigate the correlation between self-management, psychological resilience and stoma acceptance of colorectal cancer patients with stoma. Multiple linear regression analysis was used to explore the influencing factors of self-management in colorectal cancer patients with stoma. A total of 390 questionnaires were distributed in this study, and 386 valid questionnaires were collected, with an effective response rate of 98.97% (386/390) .Results:The self-management, psychological resilience and stoma acceptance score of colorectal cancer patients with stoma was (99.07±12.40), (69.43±9.76), (82.00±10.56). Pearson correlation analysis results showed that the score of self-management in colorectal cancer patients with stoma was positively correlated with psychological resilience and stoma acceptance scores ( r=0.640, 0.727; P<0.01). The results of multiple linear regression showed that age, time after enterostomy, tumor node metastasis (TNM) staging, postoperative radiation and chemotherapy, psychological resilience, and stoma acceptance were the influencing factors of self-management in colorectal cancer patients with stoma ( P<0.05) . Conclusions:The self-management of colorectal cancer patients with stoma is at a moderate level and needs to be improved. Medical and nursing staff should take targeted intervention measures to improve patients' self-management and quality of life.

Objective:To search, evaluate and summarize the best evidences related to induction of labor by oxytocin infusion in pregnant women with full-term pregnancy, and to provide reference for clinical practice in order to reduce the complications during labor, such as the proportion of instrument delivery, prolonged labor duration, uterine rupture, postpartum hemorrhage, etc. Standardize the management process of induction of labor with oxytocin, improve the satisfaction of pregnant women to participate in the decision of induction of labor, and improve the outcome of the newborn.Methods:Take the evidence-based nursing method, in view of the full-term pregnancy pregnant women oxytocin drip induced labor evidence-based labor management problems, nearly 10 years related literature retrieval from January 1st 2011 to April 9th, 2021, the Australian JBI evidence-based health care center of literature quality evaluation criteria and evidence classification system, all kinds of research evaluation and classification of retrieval.Results:Early detection to 340 articles, and eventually into 9 articles, including 1 clinical decision, 6 guides, 2 pieces of system evaluation. Totally 45 pieces evidences related to induction of labor by oxytocin infusion in pregnant women with full-term pregnancy were sumarized, including induced labor time, oxytocin side effects, induced labor before evaluation, induced labor of guardianship, infusion solution, such as health education, and other seven aspects.Conclusions:The present study summarized 45 pieces of best evidence on the management of labor induced by oxytocin infusion during term pregnancy, which provided some evidence-based basis for midwives, obstetric nurses and managers. Through the application of the best evidence, it is beneficial to improve the outcome of pregnant women in the neonatal perinatal period, standardize the process of inducing labor with oxytocin, and improve the quality of obstetric care.

Objective: To evaluate the performance of baseline clinical characteristics and pretherapeutic histogram parameters derived from T2 mapping of the extraocular muscles (EOMs) in the prediction of treatment response to intravenous glucocorticoid (IVGC) therapy for active and moderate-to-severe thyroid-associated ophthalmopathy (TAO) and to investigate the effect of fat-suppression (FS) in T2 mapping in this prediction. Materials and Methods: A total of 79 patients clinically diagnosed with active, moderate-to-severe TAO (47 female, 32 male;mean age ± standard deviation, 46.1 ± 10 years), including 43 patients with a total of 86 orbits in the responsive group and 36 patients with a total of 72 orbits in the unresponsive group, were enrolled. Baseline clinical characteristics and pretherapeutic histogram parameters derived from T2 mapping with FS (i.e., FS T2 mapping) or without FS (i.e., conventional T2 mapping) of EOMs were compared between the two groups. Independent predictors of treatment response to IVGC were identified using multivariable analysis. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the predictive performance of the prediction models. Differences between the models were examined using the DeLong test. Results: Compared to the unresponsive group, the responsive group had a shorter disease duration, lower kurtosis (FSkurtosis), lower standard deviation, larger 75th, 90th, and 95th (FS-95th) T2 relaxation times in FS mapping and lower kurtosis in conventional T2 mapping. Multivariable analysis revealed that disease duration, FS-95th percentile, and FS-kurtosis were independent predictors of treatment response. The combined model, integrating all identified predictors, had an optimized area under the ROC curve of 0.797, 88.4% sensitivity, and 62.5% specificity, which were significantly superior to those of the imaging model (p = 0.013). Conclusion An integrated combination of disease duration, FS-95th percentile, and FS-kurtosis was a potential predictor of treatment response to IVGC in patients with active and moderate-to-severe TAO. FS T2 mapping was superior to conventional T2 mapping in terms of prediction.

Objective:To improve the recruitment management process of public hospitals and enhance the quality of recruitment.Methods:Through the introduction of the people capability maturity model(P-CMM), the recruitment practice system of a tertiary hospital was evaluated. The evaluation scoring was expressed as the average score±standard deviation( ± s), and the scorer′s reliability index was expressed as Kendall coefficient. Results:According to the P-CMM recruitment practice standards, a total of 16 level-1 indicators and 35 level-2 indicators were set up. Among them, there were 7 standard projects and 9 gap projects, with reasons for the gaps analyzed.Conclusions:It is necessary to enhance the strategic vision of the recruitment process, systematically implement hospital post management, build a recruitment platform based on multi-party participation, and scientifically analyze the recruitment process to further improve the recruitment quality of public hospitals.

Objective To explore the effect of posterior column stability and decompression on the treatment of lumbar burst fracture with nerve injury and its effect on vertebral body and neurological function.Methods Fifty-two cases patients of lumbar burst fracture with nerve injury from February 2005 to July 2014 in Affiliated Hospital of Youjiang Medical College For Nationalities were selected as the research objects and divided into retention group(28 cases) and non-retention group(24 cases) according to the choice of operation method.The surgical clinical efficacy,the changes of the vertebral body and nerve function were compared between two groups.Results At 3 months,6 months and 12 months after operation,the fusion rate,sagittal diameter and the height of the injured vertebral body,pre-vertebral body,and intervertebral space were all significantly increased,while the Cobb angle,the pressure area and the sagittal displacement rate were markedly decreased(F of inner grouP=10.492,8.858,7.432,16.311,19.491,10.329,21.587;P<0.05),and the improvement range of Cobb angle,intervertebral space,the pressure area and sagittal displacement rate of retention group were significant better than non-retention group.There was no significant difference on the fusion rate,the volume of bleeding,the incidence of postoperative complications,Denis pain score,the height of injured vertebral body,pre-vertebral body,and sagittal displacement between the two groups(P>0.05).After operation,the ASIA grade gradually improved,neurological function of the retention group recovered at 6 months after surgery,while non-retention group presented this effect at 12 months after surgery,moreover,at 12 months after operation,the proportion of E grade in retention group was 64.29%,higher than that of non-retention group(45.83%,F=12.758,P<0.001).The levels of neuron-specific enolase(NSE),S100B protein and myelin basic protein(MBP) in retention group were significantly lower than those of the non-retention group at 3 months after surgery(P<0.05).The improvement of S100B and MBP in the reservation group at 6 months after surgery were better than those of non-retention group,while at 12 months after surgery,only the improvement of MBP in retention group showed the better effects than non-retention group.Conclusion Posterior column stability and decompression show a high clinical efficacy on the treatment of lumbar burst fracture with nerve injury and it can significantly improve the vertebral body and neurological function.