Aim To study the therapeutic effect of al-licin on senna-induced diarrhea in mice and to explore the underlying mechanism.Methods Forty-eight C57BL/6J mice were randomly divided into six groups:control,model,loperamide positive control group(2 mg·kg-1),allicin low-dose group(6 mg·kg-1),allicin medium-dose group(12 mg·kg-1)and allicin high-dose group(18 mg·kg-1).Except for the con-trol group,the diarrhea model was induced in the other groups by intragastric administration of senna leaf ex-tract.After drug administration,several diarrhea indi-ces were measured:the rate of loose stools,diarrhea index,accumulated frequency of loose stools at differ-ent time points within 5 hours,and small intestine pro-pelling rate.Serum levels of TNF-α and IL-6 were de-tected by ELISA.Serum NO content was determined u-sing the Griess method.The activities of SOD and CAT,as well as MDA content in the ileum and colon,were measured.The pathological changes and the ex-pression of mRNA related to intestinal barrier proteins in the ileum and colon were evaluated using HE stai-ning and RT-qPCR.Results Allicin improved diar-rhea symptoms in mice induced by senna leaf.It re-duced the rate of loose stools,diarrhea index,cumula-tive number of loose stools in five hours,and the intes-tinal propulsion rate.Allicin also protected the intesti-nal mucosa,decreased serum TNF-α and IL-6 levels,and lowered MDA content in the intestines.It in-creased serum NO levels and enhanced SOD and CAT activities in the intestines.Additionally,allicin upreg-ulated the mRNA expression of AQP1,AQP4,and ZO-1 in intestinal tissues.Conclusions Allicin has a significant therapeutic effect on senna-induced diarrhea in mice.The underlying molecular mechanisms may involve anti-inflammatory and antioxidant effects,in-creased NO content,and upregulation of mRNA ex-pression of aquaporins and tight-junction proteins.

Objective:To investigate the effect of uridine diphosphate ceramide galactosyltransferase 8(UGT8)on colorectal cancer(CRC)cell growth and migration,elucidate an underlying mechanism,and assess the potential regulatory role of SRY-box transcription factor 9(SOX9)on UGT8.Methods:UGT8 and SOX9 mRNA expression levels in CRC tissues,and correlation between their expression levels,were analyzed using GEPIA2,UALCAN,and TIMER 2.0 online databases.UGT8 and SOX9 protein expression in CRC and adjacent tissues was detec-ted using immunohistochemistry,and relationships between their expression and clinicopathological characteristics were analyzed.Impact of UGT8 knockdown on CRC cell proliferation was assessed using a CCK-8 assay,and cell migration was evaluated using Transwell and wound healing assays.Western blot was performed to detect expression of epithelial-mesenchymal transition(EMT)markers(E-cadherin and ZEB1).RT-qPCR and Western blot were used to measure UGT8 mRNA and protein expression levels after SOX9 knockdown.The JASPAR online database was used to assess SOX9 potential for binding to the UGT8 promoter.Results:Bioinformatics analyses revealed significantly higher mRNA expression levels of both UGT8 and SOX9 in CRC tissues than in normal tissues.Positive correlation was observed between expres-sion levels.Immunohistochemistry results showed that tumor UGT8 and SOX9 protein levels were significantly higher than those in adjacent tissues.UGT8 protein level was found to correlates with N stage,and SOX9 protein level correlated with T stage.A positive correlation was observed between UGT8 and SOX9 expression levels.Following UGT8 knockdown,cell proliferation capacity was attenuated and cell migra-tion ability was reduced.E-cadherin expression concurrently increased and ZEB1 expression decreased.RT-qPCR and Western blot results showed that SOX9 knockdown significantly reduced UGT8 mRNA and protein levels.The JASPER website predicts that SOX9 will bind to the UGT8 promoter.Conclusions:UGT8 and SOX9 are highly expressed in CRC tissues,and their expression levels correlate with clinicopatholo-gical features.UGT8 and SOX9 expression levels display significant positive correlation.Mechanistically,UGT8 promotes CRC cell prolifera-tion and migration by facilitating epithelial-mesenchymal transition(EMT).SOX9 enhances UGT8 mRNA and protein expression and may bind to the UGT8 promoter region.

Objective:To construct an indicator system for a nursing science and technology innovation curriculum guided by innovation competence, in order to provide a reference for cultivating innovation ability in nursing students.Methods:The overall research period was from March to December 2024. A nursing innovation curriculum indicator framework was initially developed through literature analysis and brainstorming. From October to December 2024, 19 experts from nine hospitals or universities across five provinces and cities were selected via purposive sampling to participate in two rounds of Delphi consultation. Revisions were made based on expert feedback.Results:Both rounds of expert consultation achieved a 100% response rate. The authority coefficient of the experts was 0.92. The final indicator system included four curriculum elements: course content, course objectives, teaching methods, and assessment, encompassing 14 first-level indicators and 40 second-level indicators.Conclusions:The innovation-oriented indicator system for nursing science and technology education demonstrates good scientific validity and reliability. It offers a foundational framework for advancing innovation-focused nursing education and curriculum design.

Aim To study the therapeutic effect of al-licin on senna-induced diarrhea in mice and to explore the underlying mechanism.Methods Forty-eight C57BL/6J mice were randomly divided into six groups:control,model,loperamide positive control group(2 mg·kg-1),allicin low-dose group(6 mg·kg-1),allicin medium-dose group(12 mg·kg-1)and allicin high-dose group(18 mg·kg-1).Except for the con-trol group,the diarrhea model was induced in the other groups by intragastric administration of senna leaf ex-tract.After drug administration,several diarrhea indi-ces were measured:the rate of loose stools,diarrhea index,accumulated frequency of loose stools at differ-ent time points within 5 hours,and small intestine pro-pelling rate.Serum levels of TNF-α and IL-6 were de-tected by ELISA.Serum NO content was determined u-sing the Griess method.The activities of SOD and CAT,as well as MDA content in the ileum and colon,were measured.The pathological changes and the ex-pression of mRNA related to intestinal barrier proteins in the ileum and colon were evaluated using HE stai-ning and RT-qPCR.Results Allicin improved diar-rhea symptoms in mice induced by senna leaf.It re-duced the rate of loose stools,diarrhea index,cumula-tive number of loose stools in five hours,and the intes-tinal propulsion rate.Allicin also protected the intesti-nal mucosa,decreased serum TNF-α and IL-6 levels,and lowered MDA content in the intestines.It in-creased serum NO levels and enhanced SOD and CAT activities in the intestines.Additionally,allicin upreg-ulated the mRNA expression of AQP1,AQP4,and ZO-1 in intestinal tissues.Conclusions Allicin has a significant therapeutic effect on senna-induced diarrhea in mice.The underlying molecular mechanisms may involve anti-inflammatory and antioxidant effects,in-creased NO content,and upregulation of mRNA ex-pression of aquaporins and tight-junction proteins.

miR-101-3p is an evolutionarily conserved non-coding RNA that has shown aberrant expression and regulatory functios in various cardiovascular diseases(CVDs)in recent years.It participates in key pathological processes including post-infarction myocardial remodeling,myocardial fibrosis in heart failure and the development of atherosclerosis by modulating pathways such as apoptosis,autophagy and metabolism.In addition,it exhibits immunoregulatory potential in myocardium injury related to systemic diseases.This review summarizes the recent advances in understanding the role of miR-101-3p in CVDs,focusing on its expression dynamics and regulatory mechanisms in different disease models.It further elaborates on the biological effects of miR-101-3p in cardiovascular pathology and explores its potential as a diagnostic biomarker and therapeutic target.miR-101-3p is expected to provide novel insights for early detection and targeted intervention of cardiovascular diseases.

miR-101-3p is an evolutionarily conserved non-coding RNA that has shown aberrant expression and regulatory functios in various cardiovascular diseases(CVDs)in recent years.It participates in key pathological processes including post-infarction myocardial remodeling,myocardial fibrosis in heart failure and the development of atherosclerosis by modulating pathways such as apoptosis,autophagy and metabolism.In addition,it exhibits immunoregulatory potential in myocardium injury related to systemic diseases.This review summarizes the recent advances in understanding the role of miR-101-3p in CVDs,focusing on its expression dynamics and regulatory mechanisms in different disease models.It further elaborates on the biological effects of miR-101-3p in cardiovascular pathology and explores its potential as a diagnostic biomarker and therapeutic target.miR-101-3p is expected to provide novel insights for early detection and targeted intervention of cardiovascular diseases.

Objective:To investigate the effects of two anastomosis methods on perioperative and pathological outcomes during totally laparoscopic right hemicolectomy (TLRH).Methods:In a national multicenter snapshot study, 1,854 patients who underwent laparoscopic right hemicolectomy were enrolled from 52 tertiary hospitals across China. The post-hoc analysis based on this study compared the data of 303 patients who underwent TLRH. Patients were divided into the antiperistaltic group (33 cases) and the isoperistaltic group (270 cases) according to type of anastomosis. Due to the significant difference in sample size between the two groups, propensity score matching (PSM) was performed to eliminate the influence of baseline characteristic discrepancies. The matching was based on the following known confounding factors: age, gender, body mass index (BMI), history of abdominal surgery, and history of diabetes, with a caliper value of 0.2. Perioperative and pathological outcomes were compared between the two groups.Results:After PSM, 33 patients were included in the antiperistaltic group and 65 patients in the isoperistaltic group. There were no statistically significant differences in baseline data between the two groups (all P>0.05). No significant differences were observed between the two groups in terms of operation time, blood loss, time to first defecation, time to first oral intake, or the incidence and grading of complications either (all P>0.05). However, length of postoperative hospital stay in the isoperistaltic group was significantly shorter than that in the antiperistaltic group, however (7.0 [6.0, 9.0] days vs. 8.0 [7.0, 10.5] days, P=0.049). In terms of pathological outcomes, there were also no statistically significant differences between the two groups in the number of harvested lymph nodes or the number of positive lymph nodes (all P>0.05). Conclusions:The two digestive tract reconstruction modalities, antiperistaltic and isoperistaltic anastomosis, have comparable perioperative safety and efficacy in TLRH. The isoperistaltic group had better outcomes in terms of postoperative hospital stay.

BACKGROUND: PANoptosis has the features of pyroptosis, apoptosis, and necroptosis. Numerous studies have confirmed the diverse roles of various types of cell death in acute liver failure (ALF), but limited attention has been given to the crosstalk among them. In this study, we aimed to explore the role of PANoptosis in ALF and uncover new targets for its prevention or treatment. METHODS: Three ALF-related datasets (GSE14668, GSE62029, and GSE74000) were downloaded from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). Hub genes were identified through intersecting DEGs, genes obtained from weighted gene co-expression network analysis (WGCNA), and genes related to PANoptosis. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein‍‒‍protein interaction (PPI) analyses and gene set enrichment analysis (GSEA) were performed to determine functional roles. Verification was performed using an ALF mouse model. RESULTS: Our results showed that expression of seven hub genes (B-cell lymphoma-2-modifying factor (BMF), B-cell lymphoma-2-interacting protein 3-like (BNIP3L), Caspase-1 (CASP1), receptor-interacting protein kinase 3 (RIPK3), uveal autoantigen with coiled-coil domains and ankyrin repeats protein (UACA), uncoordinated-5 homolog B receptor (UNC5B), and Z-DNA-binding protein 1 (ZBP1)) was up-regulated in liver samples of patients. However, in the ALF mouse model, the expression of BNIP3L, RIPK3, phosphorylated RIPK3 (P-RIPK3), UACA, and cleaved caspase-1 was up-regulated, while the expression of CASP1 and UNC5B was down-regulated. The expression of ZBP1 and BMF increased only during the development of ALF, and there was no significant change in the end stage. Immunofluorescence of mouse liver tissue showed that macrophages expressed all seven markers. Western blot results showed that pyroptosis, apoptosis, and necroptosis were always involved in lipopolysaccharide (LPS)/ d-galactosamine (d-gal)‍-induced ALF mice. The ALF cell model showed that bone marrow-derived macrophages (BMDMs) form PANoptosomes after LPS stimulation. CONCLUSIONS: Our results suggest that PANoptosis of macrophages promotes the development of ALF. The seven new ALF biomarkers identified and validated in this study may contribute to further investigation of diagnostic markers or novel therapeutic targets of ALF.
Animals ; Liver Failure, Acute/genetics* ; Computational Biology ; Mice ; Pyroptosis/genetics* ; Humans ; Protein Interaction Maps ; Apoptosis/genetics* ; Necroptosis/genetics* ; Gene Regulatory Networks ; Gene Ontology ; Gene Expression Profiling ; Disease Models, Animal

HDAC7, a member of class IIa HDACs, plays a pivotal regulatory role in tumor, immune, fibrosis, and angiogenesis, rendering it a potential therapeutic target. Nevertheless, due to the high similarity in the enzyme active sites of class IIa HDACs, inhibitors encounter challenges in discerning differences among them. Furthermore, the substitution of key residue in the active pocket of class IIa HDACs renders them pseudo-enzymes, leading to a limited impact of enzymatic inhibitors on their function. In this study, proteolysis targeting chimera (PROTAC) technology was employed to develop HDAC7 drugs. We developed an exceedingly selective HDAC7 PROTAC degrader B14 which showcased superior inhibitory effects on cell proliferation compared to TMP269 in various diffuse large B cell lymphoma (DLBCL) and acute myeloid leukemia (AML) cells. Subsequent investigations unveiled that B14 disrupts BCL6 forming a transcriptional inhibition complex by degrading HDAC7, thereby exerting proliferative inhibition in DLBCL. Our study broadened the understanding of the non-enzymatic functions of HDAC7 and underscored the importance of HDAC7 in the treatment of hematologic malignancies, particularly in DLBCL and AML.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome