Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective To evaluate the role and potential mechanism of apolipoprotein E(APOE)in drug resistance of colon cancer by bioinformatic tools and cellular experiments.Methods After downloading the microarray dataset GSE196900 from the GEO database,the online tool GEO2R was used to identify genes that were expressed differently in the drug-resistant and control groups.The differently expressed genes were then examined for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment.The STRING database and Cytoscape software were used to build protein-protein interaction(PPI)networks and find hub genes.Hub genes'predictive significance in colon cancer was further assessed.Western blod and qRT-PCR were used to identify changes in APOE expression,whereas Transwell was used to identify changes in the colon cancer cells'capacity for invasion and migration.Results The analysis of GO and KEGG enrichment revealed that the differential genes derived from the GSE196900 dataset were primarily focused on receptor-ligand activity and cytokine-cytokine receptor interaction pathways.Using the CytoNCA plug-in in Cytoscape software,ten hub genes were obtained through PPI construction.Of these,the prognosis of the patients with colon cancer was negatively correlated with the expression of the APOE gene(P<0.05)and the overexpression of the APOE gene might significantly increase the migration and nvasivenessability of colon cancer cells(P<0.05).Conclusion The increased expression of APOE significantly promotes the migration and invasion ability of colon cancer cells,which may be one of the mechanisms by which APOE gene promotes tumor progression in the patients with colon cancer.

This paper reviews the concepts, status, influencing factors and interventions of home self-management of diabetic foot ulcers patients, with a view to providing reference for establishing and improving the home self-management model of diabetic foot ulcers patients suitable for China.

Triangle chronic disease stratified management model, as an effective chronic disease management model, can divide patients into different levels according to the stratified disease assessment criteria, enhance intervention effectiveness, improve management efficiency, and reduce costs by implementing targeted and personalized nursing measures. This article summarizes the overview of the Triangle chronic disease stratified management model, research progress at home and abroad, and the current application status in transitional care for chronic disease patients in order to provide a reference for medical staff to carry out transitional care for chronic disease patients.

Objective:To explore the therapeutic effect of cognitive behavioral therapy (CBT) combined with family intervention on obsessive-compulsive disorder (OCD).Method:A total of 28 patients with OCD who visited the outpatient department of Xiamen Xianyue Hospital from June 2021 to June 2022 were randomly divided into intervention group( n=13)and control group( n=15).Patients in the intervention group and the control group were both received routine drug treatment. On this basis, the patients in intervention group received the treatment of CBT combined with family intervention, while the patients in control group only received CBT treatment.The participants were evaluated at baseline, post-intervention, 1 month and 3 months after the intervention. The Yale-Brown obsessive compulsive scale (Y-BOCS) was used to evaluate the severity of symptoms, and the Sheehan disability scale (SDS) was used to assess their function impairment in patients.The family accommodation scale for OCD interviewer-rated (FAS-IR) was employed to assess family members' family accommodation behavior. Changes in scores on the Y-BOCS scale, SDS scale, and FAS-IR scale scores at each observation time point were used as outcome indicators. The t-test, χ2-test and repeated measure ANOVA were used for statistical analysis by SPSS 25.0 software. Results:(1)The interaction effect of Y-BOCS score between time and group before and after intervention was significant ( F=4.748, P<0.05). The results of the simple effects test showed that the Y-BOCS score of the intervention group at 1 month after the intervention(20.63±5.23)was lower than that of the baseline(27.23±5.12)and post-intervention(24.85±5.94)(both P<0.05). The Y-BOCS score of the intervention group at 3 months after the intervention (16.85±4.62)was lower than that of the baseline, post-intervention, and 1 month after the intervention (all P<0.05). The Y-BOCS score of the control group at 3 months after the intervention(20.93±7.51) was lower than that of the baseline(25.93±4.68)and post-intervention(25.53±6.57)(both P<0.05).(2)The interaction effect of SDS score between time and group before and after intervention was significant ( F=54.88, P<0.01). The results of the simple effects test showed that the SDS score of the intervention group at post-intervention was lower than that of the baseline( P<0.05).The SDS score at 1 month after the intervention was lower than that of the baseline and post-intervention (both P<0.05). The SDS score of the intervention group at 3 months after the intervention was lower than that of the baseline, post-intervention, and 1 month after the intervention (all P<0.05). At 3 months after the intervention, the SDS score of the intervention group was lower than that of the control group ( P<0.05).(3)The interaction effect of FAS-IR score between time and group before and after intervention was significant ( F=20.285, P<0.01). The results of the simple effects test showed that post-intervention, the FAS-IR score of the intervention group was lower than that of the baseline( P<0.05).The SDS score at 1 month after the intervention was lower than the baseline and post-intervention (both P<0.05). The FAS-IR score of the intervention group at 3 months after the intervention was lower than that of the baseline, post-intervention, and 1 month after the intervention (all P<0.05). At 3 months after the intervention, the FAS-IR score of the intervention group was lower than that of the control group ( P<0.05). Conclusion:The CBT combined with family intervention can improve the treatment outcome of OCD, patients' functional impairment, and reduce the occurrence of family accommodation behavior, which providing a basis for family intervention in OCD.

Objective: The purpose of this study was to investigate the different categories of males within two groups, namely a community male sample who engaged in online sexual activities (OSAs) and a subclinical male sample who were out of control in viewing pornography and had sought help. Additionally, the study aimed to determine the threshold for excessive OSAs in both samples. Methods: A total of 568 community adult males who engaged in OSAs and 567 adult males seeking help for pornography use were recruited online. A latent profile analysis (LPA) was used to identify potential profiles within the samples. Cut-point analyses were conducted to determine optimal cutoff scores for OSAs in each sample. Results: The LPA revealed two categories with different cutoff scores for OSAs within each sample. Excessive OSA can be a screening tool for detecting out-of-control behavior. More stringent criteria for identifying excessive OSAs can aid in distinguishing problematic pornography use (PPU) from impaired control in viewing sexually-explicit materials (SEMs). Two subcategories of loss of control emerged: high OSAs frequency impaired control and high viewing SEMs impaired control. Conclusion The threholds of excessive OSAs varies among community and sub-clinical male samples; this knowledge can assist in screening out individuals with impaired control and selecting individuals with PPU from the subclinical sample.

Objective: The purpose of this study was to investigate the different categories of males within two groups, namely a community male sample who engaged in online sexual activities (OSAs) and a subclinical male sample who were out of control in viewing pornography and had sought help. Additionally, the study aimed to determine the threshold for excessive OSAs in both samples. Methods: A total of 568 community adult males who engaged in OSAs and 567 adult males seeking help for pornography use were recruited online. A latent profile analysis (LPA) was used to identify potential profiles within the samples. Cut-point analyses were conducted to determine optimal cutoff scores for OSAs in each sample. Results: The LPA revealed two categories with different cutoff scores for OSAs within each sample. Excessive OSA can be a screening tool for detecting out-of-control behavior. More stringent criteria for identifying excessive OSAs can aid in distinguishing problematic pornography use (PPU) from impaired control in viewing sexually-explicit materials (SEMs). Two subcategories of loss of control emerged: high OSAs frequency impaired control and high viewing SEMs impaired control. Conclusion The threholds of excessive OSAs varies among community and sub-clinical male samples; this knowledge can assist in screening out individuals with impaired control and selecting individuals with PPU from the subclinical sample.

Objective: The purpose of this study was to investigate the different categories of males within two groups, namely a community male sample who engaged in online sexual activities (OSAs) and a subclinical male sample who were out of control in viewing pornography and had sought help. Additionally, the study aimed to determine the threshold for excessive OSAs in both samples. Methods: A total of 568 community adult males who engaged in OSAs and 567 adult males seeking help for pornography use were recruited online. A latent profile analysis (LPA) was used to identify potential profiles within the samples. Cut-point analyses were conducted to determine optimal cutoff scores for OSAs in each sample. Results: The LPA revealed two categories with different cutoff scores for OSAs within each sample. Excessive OSA can be a screening tool for detecting out-of-control behavior. More stringent criteria for identifying excessive OSAs can aid in distinguishing problematic pornography use (PPU) from impaired control in viewing sexually-explicit materials (SEMs). Two subcategories of loss of control emerged: high OSAs frequency impaired control and high viewing SEMs impaired control. Conclusion The threholds of excessive OSAs varies among community and sub-clinical male samples; this knowledge can assist in screening out individuals with impaired control and selecting individuals with PPU from the subclinical sample.

Bipolar affective disorder refers to a category of mood disorders characterized clinically by the presence of both manic or hypomanic episodes and depressive episodes.Lithium stands out as the primary pharmacological intervention for managing bipolar affective disorder.However,its therapeutic dosage closely approaches toxic levels.Toxic symptoms appear when the blood lithium concentration surpasses 1.4 mmol/L,typically giving rise to gastrointestinal and central nervous system reactions.Cardiac toxicity is rare but serious in cases of lithium poisoning.The study reports a case of a patient with bipolar affective disorder who reached a blood lithium concentration of 6.08 mmol/L after the patient took lithium carbonate sustained-release tablets beyond the prescribed dosage daily and concurrently using other mood stabilizers.This resulted in symptoms such as arrhythmia,shock,impaired consciousness,and coarse tremors.Following symptomatic supportive treatment,including blood dialysis,the patient's physical symptoms gradually improved.It is necessary for clinicians to strengthen the prevention and recognition of lithium poisoning.