Alzheimer's disease(AD)is a multifactorial degenerative disorder of the central nervous system that mainly manifests as cognitive dysfunction and loss of speech.In recent years,the zebrafish has attracted extensive attention because of its high homology with humans in terms of brain structure and function,nerve conduction,and pathogenic genes of AD.This article reviews the advantages of the zebrafish as an animal model of AD,covering topics in the pathogenesis of AD and the evaluation and screening of drugs for treatment of AD.The overall goal is to provide new insights into the pathogenesis of AD and development of novel drugs.

Detailed characterizations of genomic alterations have not identified subtype-specific vulnerabilities in adult gliomas. Mapping gliomas into developmental programs may uncover new vulnerabilities that are not strictly related to genomic alterations. After identifying conserved gene modules co-expressed with EGFR or PDGFRA (EM or PM), we recently proposed an EM/PM classification scheme for adult gliomas in a histological subtype- and grade-independent manner. By using cohorts of bulk samples, paired primary and recurrent samples, multi-region samples from the same glioma, single-cell RNA-seq samples, and clinical samples, we here demonstrate the temporal and spatial stability of the EM and PM subtypes. The EM and PM subtypes, which progress in a subtype-specific mode, are robustly maintained in paired longitudinal samples. Elevated activities of cell proliferation, genomic instability and microenvironment, rather than subtype switching, mark recurrent gliomas. Within individual gliomas, the EM/PM subtype was preserved across regions and single cells. Malignant cells in the EM and PM gliomas were correlated to neural stem cell and oligodendrocyte progenitor cell compartment, respectively. Thus, while genetic makeup may change during progression and/or within different tumor areas, adult gliomas evolve within a neurodevelopmental framework of the EM and PM molecular subtypes. The dysregulated developmental pathways embedded in these molecular subtypes may contain subtype-specific vulnerabilities.
Humans ; Brain Neoplasms/pathology* ; Neoplasm Recurrence, Local/metabolism* ; Glioma/pathology* ; Neural Stem Cells/pathology* ; Oligodendrocyte Precursor Cells/pathology* ; Tumor Microenvironment

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Objective:To explore the relationship between emotional trauma and depressive symptoms.Methods:In November 2021, a total of 1 650 university students were assessed using scales including childhood trauma questionnaire (CTQ), distress tolerance scale (DTS), rumination response scale (RRS) and the depression anxiety stress scale (DASS). SPSS 20.0 and AMOS 25.0 software were used to analyze the data with Spearman correlation analysis, Mann-Whitney U test and mediation analysis. Results:The differences of DTS, RRS and DASS were significant between high and low trauma group(all P<0.01). Emotional trauma (16.70(6.09)) was negatively correlated with distress tolerance(10.95(2.15)) ( r=-0.26, P<0.01), and positively correlated with rumination(39.51(10.74)) and depression(4.93(5.76)) ( r=0.31, 0.38, both P<0.01). The testing of mediating effect indicated that emotional trauma had direct effect ( β=0.20, P<0.001) and indirect effect on depression through distress tolerance and rumination. Conclusion:Emotional trauma, distress tolerance and rumination are important factors influencing depression, and it could provide guidance for undergraduate psychological intervention of depression.

Objective : To construct a cell-free DNA ( cfDNA) methylation model for early screening in male pa- tients with gastric cancer by using novel cfDNA methylation detection technology． Methods : Methylation informa- tion of the whole genome of gastric cancer patients were detected by cell-free methylated DNA immunoprecipitation and highthroughput sequencing ( cfMeDIP-seq ) technology and locate gastrogenic cfDNA． Then bioinformation methods were used to extract specific methylation labels which could distinguish GC patients and establish diagnosis model by random forest algorithm. Related validation clinical researches were also conducted. Results : 63 most sig- nificant DMR were selected to construct the cfDNA methylation model based on GC samples and normal control samples，the goal sensitivity was above 85 percent while the goal specificity was above 95% ．The sensitivity and specificity of the validation set were 98. 7% and 99. 0% while the area under curve(AUC) was 0. 999． Conclusion The cfDNA methylation model constructed in this study has good performance in predicting GC.

OBJECTIVE：To explore th e applicatio n of team situatio nal simulation education and teaching mode in clinical pharmacy teaching. METHODS ：A total of 60 clinical pharmacy interns were selected as the research objects ，and course disease was type 2 diabetes mellitus. Thirty interns were randomly selected as control group ，using traditional teaching mode ；other 30 interns were selected as trial group ，which carried out team situational simulation education and teaching mode. The teaching effects were evaluated by using the satisfaction of interns to the two modes ，the comprehensive score of graduation examination and the self-evaluation of learning effect. RESULTS ：Compared with traditional teaching mode ，team situational simulation education and teaching mode was conducive to stimulate the learning interest of interns ，improve their interpersonal communication ability ， cultivate teamwork spirit ，improve the awareness of humanistic care ，and cultivate the professional attitude of clinical pharmacists （P＜0.05）. Compared with control group ，the comprehensive score of trial group was dominantly increased （P＜0.001），and the scores of professional quality ，humanistic care and communication skills in the trial group were significantly higher than control group（P＜0.01）. In terms of self-evaluation of learning effect ，except for the pathogenesis of type 2 diabetes and the commonly used treatment regimens ，the self-evaluation scores of the other items in trial group were significantly higher than control group （P＜0.05 or P＜0.01）. CONCLUSIONS ：Team situational simulation education and teaching mode is superior to traditional teaching mode for clinical pharmacy teaching.

Objective: To explore the relationship among self-regulatory focus and depression, anxiety symptoms and suicidal risks of medical college students. Methods: A total of 2 251 freshmen were recruited from a medical university by convenienee sampling methood. A cross-sectional questionnaire survey using Regulatory Focus Questionnaire (RFQ), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), Beck Hopelessness Scale (BHS), Psychache Scale (PAS), and Suicide Behaviors Questionnaire-Revised (SBQ-R) was conducted. Results: The prevalence rate of freshmen’s depression symptoms was as high as 20.4%, the prevalence rate of anxiety symptoms was 11.2%, and the risk of suicide increased by 5.85 times among students with depression-anxiety comorbid symptoms. Girls reported higher prevention focused scores than boys, as well as higher anxiety symptoms and suicidal risks(t=4.84,2.18,5.57,P<0.05). College students with a prevention focused self-regulation style had significantly higher scores on depression, anxiety symptoms and suicidal risks than those with a promotion focused regulatory style, the effect sizes of the differences were moderate or large (Cohen’s d>0.50). Conclusion Self-regulatory focus plays an important role in emotional health. The pursuit of promotion goals is beneficial to mental health, while the pursuit of prevention goals is more likely to be associated with depression, anxiety symptoms and a higher risk of suicide.

OBJECTIVE：To study spectrum-effect relationship of 11 different solvent extracts from Trollius chinensis against hypoxia/reoxygenation injury of cardiomyocyte . METHODS ：HPLC-MS/MS method was used to establish the fingerprints of 11 different solvent extracts from T. chinensis ，the compounds corresponding to the common peaks were identified by comparing with the substance control and literature information. MTT assay was used to detect the effects of 11 different solvent extracts from T. chinensis on the survival rate of rat myocardial H 9c2 cells injured by hypoxia/reoxygenation. The MDA content ，ROS level in cells and LDH content in the supernatant were detected by ELISA. GRA and PLS method were used to analyze the spectrum-effect relationship between the compounds corresponding to common peak and anti-hypoxia/reoxygenation injury of cardiomyocyte （drug effect）. RESULTS ：There were 22 common peaks in 11 different solvent extracts from T. chinensis ，and 22 compounds were identified. Compared with hypoxia/reoxygenation injury group ，survival rate of hypoxia/reoxygenation injury+S 1-S6，S9 and S 10 groups were increased significantly ，while MDA content ，ROS level and LDH content were decreased significantly （P＜0.05）； ROS level and LDH content of hypoxia/reoxygenation injury+S 8 group w ere decreased significantly （P＜0.05）. The r of GRA analysis of 22 compounds with drug effects were all higher than 0.8. Except for peaks 1，2，7，13，14 and 21，r of PLS analysis of rest peaks with drug effects were higher than 0 发。电话：0431-86058683。E-mial：nml2000@163.com （being positive correlation ）. Top 9 common peaks in the list of contribution rate were peak 6＞11＞4＞5＞8＞9＞12＞10＞15. CONCLUSIONS ：Orientin（peak 6），vitexin（peak 11）， orientin-2″-O-β-L-galacto- pyranosl （peak 4），orientin-2″-O-β-D-Pyrine xylosides （peak 5），quercetin-3-O-glucopyranoside（peak 8），vitexin-2″-O-β-L-galactoside（peak 9），hyperoside（peak 12），vitexin-2″-O-β-D-pyrine xylosides （peak 10），2″-O-（2″′- methylbutyry-loxy）-orientin（peak 15）may be the main components of anti-hypoxia/reoxygenation injury of cardiomyocytes.

Objective:To evaluate the heterogeneity in pediatric ETV6-RUNX1 acute lymphoblastic leukemia (ALL) by gene expression profile and to study clinical characteristics in different clusters.Methods:An improved advanced fragment analysis (iAFA) technique was developed to detect 57 marker genes in 264 pediatric ALL patients treated in Beijing Children’s Hospital from August 2016 to June 2019. The 56 ALL patients with ETV6-RUNX1 positive were evaluated by clinical characteristics in gene expression profile, immunophenotype and early response of chemotherapy in different clusters.Results:The 56 ETV6-RUNX1-positive patients were clustered into 2 groups of E/R-1 (45, 80.4%) and E/R-2 (11, 19.6%) . Spearman coefficient was 0.788 and 0.901 in E/R-2 and E/R-1, respectively. The median of initial platelet counts was 104 (27-644) and 50 (8-390) ( P<0.01) in E/R-2 and E/R-1, respectively. The median of proportion of initial bone marrow immature cells was 0.830 (0.270-0.975) and 0.935 (0.445-0.990) ( P<0.05) in E/R-2 and E/R-1, respectively. The most specific immunophenotype at initial diagnosis, CD22 +CD34 +CD20 -CD117 -CD56 -, mainly gathered in E/R-2 ( P<0.001) . Patients negative of minimal residual disease detected by flow cytometry (MRD-FCM) at day 33 were 5 (55.6%) and 32 (88.9%) in E/R-2 and E/R-1, respectively. There was no significant difference in the original analysis ( P=0.064) but difference in sensitivity analysis ( P=0.035) . Nevertheless, patients negative of MRD detected by polymerase chain reaction (MRD-PCR) at day 33 were 7 (77.8%) and 36 (100%) in E/R-2 and E/R-1, respectively, with significant difference ( P=0.047) . Conclusion:Gene expression profile shows heterogeneous in ETV6-RUNX1 ALL, and the E/R-2 profile indicates that these patients may have a less tendency to thrombocytopenia at the initial diagnosis but have poorer response to induction chemotherapy and may influence further outcome.

Objective: To investigate the value of combination of A²DS² score, procalcitonin (PCT) and C-reactive protein (CRP) predicting stroke-associated pneumonia (SAP) in patients with acute ischemic stroke. Methods: Patients with acute ischemic stroke admitted to the Department of Neurology, Suqian People's Hospital of Nanjing Drum Tower Hospital Group from March 2015 to March 2019 were enrolled retrospectively. Multivariate logistic regression analysis was used to determine the independent correlation of A²DS² scores as well as PCT and CRP levels with SAP. Receiver operating characteristic (ROC) curves were used to assess the individual and combined predictive values of A²DS² scores, PCT and CRP levels for SAP. Results: A total of 332 patients with acute ischemic stroke were enrolled, and 58 of them developed SAP (17.5%). After adjusting for age, smoking, and hyperlipidemia, the A²DS² score (odds ratio [OR] 1.613, 95% confidence interval [CI] 1.092-2.389), PCT (OR 8.047, 95% CI 3.012-16.138) and CRP (OR 1.409, 95% CI 1.064-2.672) were the independent predictors of SAP occurrence. ROC curve analysis showed that the area under the curve of A²DS² score, PCT and CRP alone, and the combination of the three for predicting SAP were 0.811, 0.825, 0.804 and 0.910, respectively. When the three are jointly used to predict SAP, the area under the curve is significantly higher than the individual prediction (all P<0.001). Conclusions The combination of A²DS² score, PCT and CRP can improve the ability to predict SAP.