BACKGROUND: The transcription factor POU2F1 regulates the expression levels of microRNAs in neoplasia. However, the miR-29b1/a cluster modulated by POU2F1 in gastric cancer (GC) remains unknown. METHODS: Gene expression in GC cells was evaluated using reverse-transcription polymerase chain reaction (PCR), western blotting, immunohistochemistry, and RNA in situ hybridization. Co-immunoprecipitation was performed to evaluate protein interactions. Transwell migration and invasion assays were performed to investigate the biological behavior of GC cells. MiR-29b1/a cluster promoter analysis and luciferase activity assay for the 3'-UTR study were performed in GC cells. In vivo tumor metastasis was evaluated in nude mice. RESULTS: POU2F1 is overexpressed in GC cell lines and binds to the miR-29b1/a cluster promoter. POU2F1 is upregulated, whereas mature miR-29b-3p and miR-29a-3p are downregulated in GC tissues. POU2F1 promotes GC metastasis by inhibiting miR-29b-3p or miR-29a-3p expression in vitro and in vivo . Furthermore, PIK3R1 and/or PIK3R3 are direct targets of miR-29b-3p and/or miR-29a-3p , and the ectopic expression of PIK3R1 or PIK3R3 reverses the suppressive effect of mature miR-29b-3p and/or miR-29a-3p on GC cell metastasis and invasion. Additionally, the interaction of PIK3R1 with PIK3R3 promotes migration and invasion, and miR-29b-3p , miR-29a-3p , PIK3R1 , and PIK3R3 regulate migration and invasion via the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in GC cells. In addition, POU2F1 , PIK3R1 , and PIK3R3 expression levels negatively correlated with miR-29b-3p and miR-29a-3p expression levels in GC tissue samples. CONCLUSIONS The POU2F1 - miR-29b-3p / miR-29a-3p-PIK3R1 / PIK3R1 signaling axis regulates tumor progression and may be a promising therapeutic target for GC.
MicroRNAs/metabolism* ; Humans ; Stomach Neoplasms/pathology* ; Cell Line, Tumor ; Cell Movement/physiology* ; Phosphatidylinositol 3-Kinases/metabolism* ; Animals ; Mice ; Octamer Transcription Factor-1/metabolism* ; Mice, Nude ; Class Ia Phosphatidylinositol 3-Kinase/metabolism* ; Neoplasm Invasiveness ; Gene Expression Regulation, Neoplastic/genetics* ; Male ; Immunohistochemistry ; Female

Alzheimer's disease (AD) is a neurodegenerative disease with clinical hallmarks of progressive cognitive impairment. Synergistic effects of the Aβ-Tau cascade reaction are tightly implicated in AD pathology, and microglial NLRP3 inflammasome activation drives neuronal tauopathy. However, the underlying mechanism of how Aβ mediates NLRP3 inflammasome remains unclear. Herein, we determined that oligomeric Aβ (o-Aβ) bound to microglial Kv2.1 and promoted Kv2.1-dependent potassium efflux to activate NLRP3 inflammasome resulting in neuronal tauopathy by using Kv2.1 inhibitor drofenine (Dfe) as a probe. The underlying mechanism has been intensively investigated by assays with Kv2.1 knockdown in vitro (si-Kv2.1) and in vivo (AAV-ePHP-si-Kv2.1). Dfe deprived o-Aβ of its capability to promote microglial NLRP3 inflammasome activation and neuronal Tau hyperphosphorylation by inhibiting the Kv2.1/JNK/NF-κB pathway while improving the cognitive impairment of 5×FAD-AD model mice. Our results have highly addressed that the Kv2.1 channel is required for o-Aβ-driven microglial NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Dfe as a Kv2.1 inhibitor shows potential in the treatment of AD.

Dendritic cells (DCs) serve as the primary antigen-presenting cells in autoimmune diseases, like rheumatoid arthritis (RA), and exhibit distinct signaling profiles due to antigenic diversity. Type II collagen (CII) has been recognized as an RA-specific antigen; however, little is known about CII-stimulated DCs, limiting the development of RA-specific therapeutic interventions. In this study, we show that CII-stimulated DCs display a preferential gene expression profile associated with migration, offering a new perspective for targeting DC migration in RA treatment. Then, saikosaponin D (SSD) was identified as a compound capable of blocking CII-induced DC migration and effectively ameliorating arthritis. Optineurin (OPTN) is further revealed as a potential SSD target, with Optn deletion impairing CII-pulsed DC migration without affecting maturation. Function analyses uncover that OPTN prevents the proteasomal transport and ubiquitin-dependent degradation of C-C chemokine receptor 7 (CCR7), a pivotal chemokine receptor in DC migration. Optn-deficient DCs exhibit reduced CCR7 expression, leading to slower migration in CII-surrounded environment, thus alleviating arthritis progression. Our findings underscore the significance of antigen-specific DC activation in RA and suggest OPTN is a crucial regulator of CII-specific DC migration. OPTN emerges as a promising drug target for RA, potentially offering significant value for the therapeutic management of RA.

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

OBJECTIVES: To explore the mechanism by which Pulsatilla saponin D (PSD) inhibits invasion and metastasis of triple-negative breast cancer (TNBC). METHODS: The public databases were used to identify the potential targets of PSD and the invasion and metastasis targets of TNBC to obtain the intersection targets between PSD and TNBC. The "PSD-target-disease" interaction network was constructed and protein-protein interaction (PPI) analysis was performed to obtain the core targets, which were analyzed for KEGG pathway and GO functional enrichment. Molecular docking study of the core targets and PSD was performed, and the therapeutic effect and mechanism of PSD were verified using Transwell assay and Western blotting in cultured TNBC cells. RESULTS: Network pharmacology analysis identified a total of 285 potential PSD targets and 26 drug-disease intersection core targets. GO analysis yielded 175 entries related to the binding of biomolecules (protein, DNA and RNA), enzyme activities, and regulation of gene transcription. KEGG analysis yielded 46 entries involving pathways in cancer, chemical carcinogenesis-receptor activation, microRNAs in cancer, chemical carcinogenesis-reactive oxygen species, PD-L1 expression and PD-1 checkpoint pathway in cancer. Molecular docking showed high binding affinities of PSD to MTOR, HDAC2, ABL1, CDK1, TLR4, TERT, PIK3R1, NFE2L2 and PTPN1. In cultured TNBC cells, treatment with PSD significantly inhibited cell invasion and migration and lowered the expressions of MMP2, MMP9, N-cadherin and the core proteins p-mTOR, ABL1, TERT, PTPN1, HDAC2, PIK3R1, CDK1, TLR4 as well as NFE2L2 expressionin the cell nuclei. CONCLUSIONS The inhibitory effects of PSD on TNBC invasion and metastasis are mediated by multiple targets and pathways.
Humans ; Triple Negative Breast Neoplasms/metabolism* ; Saponins/pharmacology* ; Pulsatilla/chemistry* ; Female ; Molecular Docking Simulation ; Cell Line, Tumor ; Neoplasm Invasiveness ; Protein Interaction Maps ; Neoplasm Metastasis ; Signal Transduction/drug effects* ; Cell Movement/drug effects*

This article introduces a high-magnification electronic endoscope system that utilizes a continuous zoom optical design,enabling high-magnification imaging at the cellular level.By selecting an appropriate initial retrofocus structure,the optimized modulation transfer function(MTF)curve of the zoom objective lens approaches the diffraction limit.Additionally,the tip and operation parts of the system incorporate modular gas-tight sealing and multiple layers of protective structure.The design employs efficient sealing materials and precise packaging techniques to ensure the system's sealing performance.The experimental results indicate that,under conventional imaging,the resolution is equivalent to 39.37 μm in object space,and the field of view angle is larger than 140 degrees.At magnified imaging,the resolution is equivalent to 2.78 μm in object space,and the observed actual field of view is greater than 800 μm×700 μm.When used with a 26-inch display monitor,the high-magnification electronic endoscope can achieve 500×optical magnification,allowing for the observation of features at the cellular level.Currently,this product has successfully achieved mass production and has undergone multiple animal trials,demonstrating its wide range of potential applications and significant clinical value.

Objective:To understand the real experience of caregivers of children with craniopharyngioma-associated hypothalamic obesity (CP-HO) based on the chronic disease trajectory model, so as to provide a reference for formulating corresponding disease management plans.Methods:From May 2023 to July 2023, semi-structured interviews were conducted with 17 caregivers of children with CP-HO who were admitted to the Department of Neurosurgery, Nanfang Hospital, Southern Medical University through purposive sampling. The interview data were analyzed by Colaizzi 7-step analysis method.Results:The 17 caregivers of children with CP-HO were 24 to 46 years old, including 3 males and 14 females. A total of 3 themes were extracted. Prodromal phase of weight: lack of disease cognition and weakening of self-concept; during the period of weight increase, the demand burden became prominent and the life pattern changed; weight stability: pressure, hope, and insight into the value of life.Conclusions:For promoting a good disease response of caregivers and improving the weight management effect of children and the quality of family life, medical staff should pay attention to and understand the disease care experience of children with CP-HO, and provide comprehensive and systematic solution strategies.

Objective:To explore the latent profiles of intellectual humility in primary colorectal cancer (CRC) postoperative patients and analyze the correlation between their intellectual humility and self-management.Methods:A total of 250 patients with primary CRC who underwent radical tumor surgery in anorectal department of Qinghai Provincial Hospital of Traditional Chinese Medicine from October 2021 to June 2023 were selected to accept a cross-sectional survey through convenient sampling method. They were surveyed by basic information questionnaire, comprehensive intellectual humility scale and cancer patient self-management assessment scale.Results:Finally, 243 valid questionnaires were obtained, it contained 125 males and 118 females with age 32- 68 (52.45 ± 10.24) years old. The score of primary CRC postoperative patients′intellectual humility was (67.59 ± 13.26) points, it could be divided into low-level intellectual humility type with 30 cases(12.34%), confident intellectual humility type with 36 cases (14.82%), mid-level intellectual humility type with 93 cases (38.27%), and high-level intellectual humility type with 84 cases (34.57%). Disordered multi-classes Logistic regression analysis showed that gender(female, OR=2.465), education level (high school or vocational school, OR=0.012) and diagnosis time(1-3 months, OR=15.289) were significant influencing factors to primary CRC postoperative patients from confident intellectual humility type (all P<0.05), gender (female, OR=5.354) and education level (high school or vocational school education, OR=0.012) were significant influencing factors to primary CRC postoperativepatients from mid-level intellectual humility type (both P<0.05), gender (female, OR=11.253), age (<45 years old, OR=7.532), education level (high school or vocational school, OR=0.017) and diagnosis time (<1 month, OR=0.054) were significant influencing factors to primary CRC postoperative patients from high-level intellectual humility type (all P<0.05). The score of primary CRC postoperative patients′self-management was (142.03 ± 19.83) points. There were statistically significant differences among scores of self-management, daily life management, symptom management and other six dimensions in patients from different categories of intellectual humility ( F values were 25.42-490.55, all P<0.05). There were positive correlation between the CRC patients′inteilectual humility and postoperatice self-managemeat ( r values were 0.373 - 0.749, all P<0.05). Conclusions:Primary CRC patients have a moderate level of knowledge humility and postoperative self-management. Their knowledge humility can be divided into low knowledge humility type, confident knowledge humility type, medium knowledge humility type, and high knowledge humility type. Knowledge humility can enhance postoperative self-management, and targeted interventions should be carried out for CRC patients with different types of knowledge humility to provide them with better cancer care and enhance their self-management level.

There are many kinds of zirconia repair materials that have been introduced at home and abroad.Mechanical and aesthetic properties are the important factors for selecting zirconia materials.The process of diagnosis and treatment by dentists and the production by the workers in laboratory affect the final repair effects.To achieve accurate and efficient simulation of dental repair and treatment,effective cooperation between dentists and technicians is required.In this paper,the factors affecting mechanical and aes-thetic properties in the process of material selection,tooth wearing,restoration design and fabrication,concerning zirconia veneer,sin-gle-crown,fixed bridge and edentulous jaw implant fixed repair were discussed and summarized.The common failure reasons were ana-lyzed in order to improve the communication efficiency between dentists and technicians in the process of zirconia repair system and to a-chieve better repair effects.

To improve the evaluation indicators of medical quality in TCM hospitals; To realize objective, fair, and accurate evaluation of the quality of TCM. Based on relevant literature on medical quality in traditional Chinese medicine hospitals research and thematic group discussions, 21 evaluation indicators for TCM characteristics were formed. A questionnaire survey was conducted among 40 experts, and 37 were effectively collected, with a positive coefficient of 92.50%. After two rounds of expert consultation, the evaluation indicators were determined to be: the intensity of outpatient use of TCM decoction pieces (utilization rate of TCM decoction pieces, prescription number of TCM decoction pieces, dosage of TCM decoction pieces, and service price of TCM decoction pieces), the intensity of the use of TCM technology (proportion of TCM technology, number of TCM projects, cost of TCM technology, and course of treatment). Case studies were conducted on relevant data from 10 departments using the operational decision support system (BI) platform of Yueyang Integrated Traditional Chinese and Western Medicine Hospital affiliated with Shanghai University of Traditional Chinese Medicine to verify the rationality of indicators. The 10 departments were analyzed and evaluated, and the results obtained were basically consistent with the actual medical quality situation of the hospital. The indicators used in this study can reflect the actual medical quality situation, and have a certain degree of scientificity, feasibility, and applicability, providing reference for improving the medical quality evaluation indicators of TCM hospitals.