ObjectiveTo investigate the anti-Alzheimer's disease （AD） effect of Dipsacus asper（DA） in the Caenorhabditis elegans model， and decipher the underlying mechanism via the peroxisome proliferator-activated receptor α （PPARα）/transcription factor EB （TFEB） pathway. MethodsFirst， transgenic AD C. elegans individuals were assigned into the blank control， model， positive control （WY14643， 20 µmol·L^-1）， and low-， medium-， and high-dose （100， 200， and 400 mg·L^-1， respectively） DA groups. The amyloid β-42 （Aβ₄₂） formation in the muscle cells， the paralysis time， and the deposition of amyloid β-protein （Aβ） in the head were detected. The lysosomal autophagy in the BV2 cell model was examined by Rluc-LC3wt/G120A. The expression levels of lysosomal autophagy-related proteins LC3Ⅱ， LC3I， LAMP2， and TFEB were detected by Western blot. Real-time quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of autophagy-related genes beclin1 and Atg5 and lysosome-related genes LAMP2 and CLN2 downstream of PPARα/TFEB. A reporter gene assay was used to detect the transcriptional activities of PPARα and TFEB. Immunofluorescence was used to detect the fluorescence intensity of PPARα， and the active components of the ethanol extract of DA were identified by UPLC-MS. RCSB PDB， Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP）， and Autodock were used to analyze the binding between the active components and PPARα-ligand-binding domain （LBD）. ResultsCompared with the model group， the positive control group and 200 and 400 mg·L^-1 DA groups showed prolonged paralysis time （P<0.05）， and all the treatment groups showed decreased Aβ deposition in the head （P<0.01）. DA within the concentration range of 50-500 mg·L^-1 did not affect the viability of BV2 cells. In addition， DA enhanced the autophagy flux （P<0.05）， up-regulated the mRNA levels of beclin1， Atg5， LAMP2， and CLN2 （P<0.05， P<0.01）， promoted the nuclear translocation of TFEB （P<0.05）， increased LAMP2 expression and autophagy flux （P<0.05， P<0.01）， and enhanced the transcriptional activities of PPARα and TFEB （P<0.01）. The positive control group and 200 and 400 mg·L^-1 DA groups showed enhanced fluorescence intensity of PPARα in the BV2 nucleus （P<0.01）. UPLC-MS detected nine known compounds of DA， from which 8 active components of DA were screened out. The docking results suggested that a variety of components in DA could bind to PPARα-LBD and form stable hydrogen bonds. ConclusionDA may reduce the pathological changes in AD by regulating the PPARα-TFEB pathway.

Objective: To analyze the space time characteristics of poor vision among primary and secondary school students in Chengdu, in order to provide the reference for formulating myopia prevention and control policies for students. Methods: The data relating to poor vision among primary and secondary school students in Chengdu from 2021 to 2023 were sourced from the Sichuan Students Physical Health Big Data Center. The districts and counties of Chengdu were divided into three circles, including the main urban area, suburban districts and counties, and suburban districts and counties. The Chi square test was used for inter group comparison, and the Cochran-Armitage test was used to analyze the trend of changes. Global and local Moran s I were used to analyze spatial clustering. Results: The detection rates of poor vision among primary and secondary school students in Chengdu from 2021 to 2023 were 62.47%, 61.61% and 60.78%, respectively, showing a decreasing trend ( Z=-32.01, P <0.01). For each year, the higher detection rate of poor vision among students was detected in the higher level of education, and differences were statistically significant ( χ 2=161 549.47, 173 471.87, 233 459.09, P <0.01). The rate of poor vision among primary and secondary school students gradually decreased from the central districts and counties of Chengdu to the surrounding districts and counties for each year, and the differences were statistically significant ( χ 2=299.20, 776.22, 633.16, P <0.01). The spatial autocorrelation analysis showed that the first circle of Chengdu City was mainly characterized by high-high agglomeration ( P <0.01), with the rate of poor vision among primary school students in Wuhou District in 2023 exhibiting a low-high anomaly. The third circle was mainly characterized by low-low aggregation ( P <0.01), while the spatial clusterings of the second circle was not significant ( P >0.05). Conclusions The myopia prevention and control work in Chengdu has achieved preliminary results. It should continue to consolidate existing achievements and implement targeted myopia prevention and control measures based on regional characteristics.

Objective: To explore the association between sleep quality and dry eye symptoms in adolescents,so as to provide the evidence for reducing the prevalence of dry eye symptoms. Methods: The study population was adolescents aged 12-24 years from the Psychology and Behavior Investigation of Chinese Residents (PBICR) survey, which was conducted from 20 June to 31 August 2022. A stratified random sampling and quota sampling method was used to select 6 456 adolescents within mainland China. The Ocular Surface Disease Index (OSDI) and Brief version of the Pittsburgh Sleep Quality Index (B-PSQI) were used to assess dry eye symptoms and sleep quality. Multiple Logistic regression model was used to explore the relationship between sleep quality and dry eye symptoms in adolescents. The influence of gender on the association was explored by using interaction terms. Results: A total of 2 815 adolescents reported having dry eye symptoms, with a prevalence of 43.6%. Logistic regression analysis results showed an increased risk of exacerbation of dry eye symptoms in adolescents with poor sleep quality. The OR (95% CI ) for mild, moderate, and severe dry eye symptoms groups were 1.39(1.16-1.67), 1.52(1.28-1.81), and 2.35(2.02-2.72), respectively, compared with the ocularly normal group ( P <0.05). There was a significant interaction between sleep quality and gender on dry eye symptoms in adolescents ( P <0.01). Conclusions Sleep quality is associated with dry eye symptoms in adolescents, and those with poor sleep quality have a higher risk of dry eye symptoms. The effect of sleep quality on dry eye symptoms is greater in boys.

BackgroundPrevious studies have identified a close relationship among psychological neglect and abuse， negative affect， different stages of adolescence， and suicidal ideation. However， the mechanisms underlying the impact of psychological abuse and neglect on suicidal ideation among left-behind adolescents remain unclear， and this field of research is still in its relative infancy. ObjectiveTo explore the relationship between psychological neglect/abuse and suicidal ideation among left-behind adolescents， as well as the mediating role of negative affect and the moderating effect of different stages of adolescence， so as to provide insights for preventing and intervening suicidal ideation in this population. MethodsFrom November 2021 to May 2022， a cluster random sampling technique was utilized to select 2 309 left-behind adolescents in western China. Assessments were conducted using the Child Psychological Abuse and Neglect Scale （CPANS）， the Positive and Negative Suicide Ideation （PANSI） and the Positive and Negative Affect Schedule for Children （PANAS-C）. Spearman correlation coefficients were calculated across all samples， and Process 4.1 was employed to test the mediating role of negative affect and the moderating role of different stages of adolescence in the pathway linking psychological abuse/neglect to suicidal ideation. ResultsA total of 2 119 left-behind adolescents （mean age： 14.94±1.20 years） completed the study， with males comprising 51.34% （1 088/2 119） and females 48.66% （1 031/2 119）.Among left-behind adolescents， scores on CPANS psychological neglect subscale showed positive correlations with both psychological abuse subscale scores and PANAS-C negative affect subscale scores （r=0.446， 0.496， P<0.01）. Additionally， CPANS psychological neglect and psychological abuse subscale scores were also positively correlated with PANSI scores （r=0.487， 0.508， P<0.01）. Furthermore， PANAS-C negative affect subscale scores demonstrated a positive correlation with PANSI scores （r=0.499， P<0.01）. Negative affect partially mediated the relationship between psychological abuse/psychological neglect and suicidal ideation， with effect sizes of 0.166 （95% CI： 0.141~0.191） and 0.131 （95% CI： 0.112~0.152）. Different stages of adolescence moderated the latter part （negative emotion → suicidal ideation） of the indirect mediation path from psychological neglect to suicidal ideation through negative affect （β=-0.066， P<0.01）. ConclusionBoth psychological neglect and psychological abuse may influence suicidal ideation among left-behind adolescents via negative affect. Moreover， different stages of adolescence may moderate the indirect path from psychological neglect to suicide ideation through negative affect.

ObjectiveTraditional Chinese medicine (TCM) constitutes a valuable cultural heritage and an important source of antitumor compounds. Poria (Poria cocos (Schw.) Wolf), the dried sclerotium of a polyporaceae fungus, was first documented in Shennong’s Classic of Materia Medica and has been used therapeutically and dietarily in China for millennia. Traditionally recognized for its diuretic, spleen-tonifying, and sedative properties, modern pharmacological studies confirm that Poria exhibits antioxidant, anti-inflammatory, antibacterial, and antitumor activities. Pachymic acid (PA; a triterpenoid with the chemical structure 3β-acetyloxy-16α-hydroxy-lanosta-8,24(31)-dien-21-oic acid), isolated from Poria, is a principal bioactive constituent. Emerging evidence indicates PA exerts antitumor effects through multiple mechanisms, though these remain incompletely characterized. Neuroblastoma (NB), a highly malignant pediatric extracranial solid tumor accounting for 15% of childhood cancer deaths, urgently requires safer therapeutics due to the limitations of current treatments. Although PA shows multi-mechanistic antitumor potential, its efficacy against NB remains uncharacterized. This study systematically investigated the potential molecular targets and mechanisms underlying the anti-NB effects of PA by integrating network pharmacology-based target prediction with experimental validation of multi-target interactions through molecular docking, dynamic simulations, and in vitro assays, aimed to establish a novel perspective on PA’s antitumor activity and explore its potential clinical implications for NB treatment by integrating computational predictions with biological assays. MethodsThis study employed network pharmacology to identify potential targets of PA in NB, followed by validation using molecular docking, molecular dynamics (MD) simulations, MM/PBSA free energy analysis, RT-qPCR and Western blot experiments. Network pharmacology analysis included target screening via TCMSP, GeneCards, DisGeNET, SwissTargetPrediction, SuperPred, and PharmMapper. Subsequently, potential targets were predicted by intersecting the results from these databases via Venn analysis. Following target prediction, topological analysis was performed to identify key targets using Cytoscape software. Molecular docking was conducted using AutoDock Vina, with the binding pocket defined based on crystal structures. MD simulations were performed for 100 ns using GROMACS, and RMSD, RMSF, SASA, and hydrogen bonding dynamics were analyzed. MM/PBSA calculations were carried out to estimate the binding free energy of each protein-ligand complex. In vitro validation included RT-qPCR and Western blot, with GAPDH used as an internal control. ResultsThe CCK-8 assay demonstrated a concentration-dependent inhibitory effect of PA on NB cell viability. GO analysis suggested that the anti-NB activity of PA might involve cellular response to chemical stress, vesicle lumen, and protein tyrosine kinase activity. KEGG pathway enrichment analysis suggested that the anti-NB activity of PA might involve the PI3K/AKT, MAPK, and Ras signaling pathways. Molecular docking and MD simulations revealed stable binding interactions between PA and the core target proteins AKT1, EGFR, SRC, and HSP90AA1. RT-qPCR and Western blot analyses further confirmed that PA treatment significantly decreased the mRNA and protein expression of AKT1, EGFR, and SRC while increasing the HSP90AA1 mRNA and protein levels. ConclusionIt was suggested that PA may exert its anti-NB effects by inhibiting AKT1, EGFR, and SRC expression, potentially modulating the PI3K/AKT signaling pathway. These findings provide crucial evidence supporting PA’s development as a therapeutic candidate for NB.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

OBJECTIVE To provide a reference for improving the relevant standard operating procedures （SOP） and biological sample management in drug clinical trials. METHODS According to Good Clinical Practice， Data On-site Verification Points of Drugs Clinical Trials， Human Genetic Resources Management Regulations Implementation Rules， Qualification Examination Rules of Drug Clinical Trials Institution， based on the experience of managing clinical trials programs， the irregularities in biological samples management were analyzed by using statistical quality control tables and protocol deviation （PD） reported by sponsors， in the context of the quality control of drug clinical trials projects managed by the author from July 2016 to May 2023. The precautions in various aspects of sample management were put forward. RESULTS & CONCLUSIONS A total of 101 biospecimen- related irregularities were found in the 60 drug clinical trials projects. Biological sample collection， preservation， and handling were the aspects with the highest incidence of irregular operations in biological sample management， accounting for 37.62%， 25.74%， and 21.78%， respectively. Regulating the management of biospecimens requires multiple efforts. The institutional office and the ethics committee carefully reviewed the consistency of the protocols， informed consent， and genetic office application involving biospecimen collection and handling when the project was initiated. Institutional office quality controllers should pay attention to the attendance and training of authorized personnel at project initiation. The principal investigator， research nurse， collector， handler， transporter， relevant personnel of the central laboratory， and institutional office quality controller have their roles during the project implementation phase. On this basis， all parties involved in the management of biological samples should do a good job of effective communication， find problems and report them in time， and conduct special studies on key aspects.

The aim is to evaluate the effect of therapeutic communication on cervical cancer patients’ preoperative anxiety and hope level. The convenience sampling method was used to select the inpatients who will receive radical surgery for cervical cancer in the department of obstetrics and gynecology of the Second Affiliated Hospital of Xi’an Jiaotong University from November 2016 to November 2019 as the research object. 50 patients were grouped by the random number table method: 25 patients were in the intervention group, and 25 patients were in the control group. Patients in the intervention group were given therapeutic communication on the basis of routine nursing, and patients in the control group were given routine nursing. Both groups were investigated with the Self-Rating Anxiety Scale (SAS) and Herth Hope Index (HHI) on the first day of admission and the day before surgery. Before the intervention, there was no statistically significant difference between the two groups (P>0.05) . After the intervention, the anxiety level of the intervention group was lower than that of the control group (P<0.05), and the hope level was higher than that of the control group (P<0.05). It can be seen that therapeutic communication can alleviate preoperative anxiety of cervical cancer patients, improve their hope level, promote patient recovery, and ease tense medical relationship.

ObjectiveTo investigate the mechanism of salvianolic acid F （Sal F） in repairing the high glucose-induced injury in human kidney-2 （HK-2） cells via the B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax）/cysteinyl aspartate-specific proteinase 3 （Caspase-3）/gasdermin-E （GSDME） pathway. MethodThe cell counting kit-8 （CCK-8） was used to measure the relative viability of HK-2 cells exposed to high glucose and different concentrations （2.5， 5， 10， 20 μmol·L^-1） of Sal F and the relative viability of HK-2 cells treated with Sal F for different time periods. The levels of lactate dehydrogenase （LDH） and interleukin-1β （IL-1β） in the supernatant of the cell culture were measured by the LDH assay kit and enzyme-linked immunosorbent assay （ELISA） kit， respectively. Flow cytometry combined with Annexin V-FITC/propidium iodide （PI） and Hoechst 33342/PI staining was employed to reveal the proportion of PI-positive HK-2 cells exposed to high glucose. Western blotting was employed to determine the protein levels of Bax， Bcl-2， cytochrome C， cysteinyl aspartate-specific proteinase （Caspase）-9， Caspase-3， and GSDME in the HK-2 cells exposed to high glucose and treated with Sal F. The 2，7-dichlorodihydrofluorescein diacetate fluorescence probe （DCFH-DA） and mitochondrial membrane potential assay kit （JC-1） were used to determine the production of reactive oxygen species （ROS） and the mitochondrial membrane potential in the HK-2 cells exposed to high glucose and treated with Sal F. ResultCompared with the blank group， the model group showed decreased cell viability （P<0.01）， elevated levels LDH and IL-1β， increased proportion of PI-positive cells （P<0.01）， up-regulated protein levels of Bax， cytochrome C， Caspase-9， Caspase-3， and GSDME （P<0.01）， down-regulated protein level of Bcl-2 （P<0.01）， decreased mitochondrial membrane potential， and excessive ROS accumulation. Compared with the model group， Sal F repaired the high glucose-induced injury in HK-2 cells （P<0.05）， lowered the levels of LDH and IL-1β （P<0.05， P<0.01）， and decreased the proportion of PI-positive cells （P<0.01）. In addition， Sal F down-regulated the protein levels of Bax， cytochrome C， Caspase-9， Caspase-3， and GSDME and up-regulated the protein level of Bcl-2 （P<0.05， P<0.01）， increased the mitochondrial membrane potential， and decreased the accumulation of ROS in HK-2 cells. ConclusionSal F can reduce the production of ROS， restore the balance of mitochondrial membrane potential， and inhibit pyroptosis via the Bax/Caspase-3/GSDME signaling pathway to repair the high glucose-induced injury in HK-2 cells.

Objective To study the risk factors of two-stage citrate anticoagulation in intermittent he-modialysis(IHD)and to establish an unplanned offline prediction model.Methods A retrospective analysis was conducted to include 34 patients and 118 times of treatment with two-stage citrate anticoagulation for IHD in the hospital from January 2019 to February 2023.According to whether the treatment did not reach the treatment time due to the coagulation of the extracorporeal circulation pipeline,118 treatments were divid-ed into the planned units(n=111)and the unplanned units(n=7).Univariate and multivariate logistic re-gression analysis were used to analyze the risk factors of unplanned weaning,and a risk prediction model was established.The receiver operating characteristic(ROC)curve was used to analyze the predictive value of the regression model.Results Univariate analysis showed that there were statistically significant differences in hematocrit(HCT),platelet count(PLT),activated partial thromboplastin time(APTT),and treatment mode between the planned and unplanned units(P<0.05).Multivariate logistic regression analysis showed that HCT and APTT were independent influencing factors for unplanned weaning(P<0.05).The HCT level was represented by A,the APTT level was represented by B,and the prediction model was:Logit(P)=1.304+ 0.206×A-0.378×B.The area under the ROC curve(AUC)of the prediction model was 0.912(95%CI:0.825-0.995,P<0.001),the maximum Youden index was 0.782,the cut off value was 0.113,the sensitivity was 85.7%,and the specificity was 92.5%.Conclusion The prediction model established by multivariate logistic regression analy-sis can make a preliminary judgment on whether coagulation occurs in two-stage IHD treatment.