Ferroptosis has been shown to mediate the development of fibrosis. Polyphyllin VII (PP7), a bioactive component of Paris polyphylla, exhibits potent anti-inflammatory activity and can significantly alleviate liver fibrosis. In this study, treatment with PP7 significantly inhibited the proliferation and activation of hepatic stellate cells (HSCs), which could be suppressed by a ferroptosis inhibitor. In addition, it promoted HSC ferroptosis by suppressing glutathione (GSH) peroxidase 4 (GPX4) and enhanced the expression of CX3C chemokine ligand 1 (CX3CL1). Depletion of CX3CL1 attenuated the effects of PP7 on the activation and ferroptosis of HSCs and the expression of GPX4. Notably, CX3CL1 directly interacted with GPX4, triggering HSC ferroptosis. The transcription factor hypermethylated in cancer 1 (Hic1), which binds to the Cx3cl1 promoter, increased the expression of CX3CL1. Its absence resulted in downregulation of CX3CL1, suppressing the GPX4-dependent ferroptosis of PP7-treated HSCs and promoting their activation. HIC1 was found to directly interact with PP7 at the GLY164 site. Co-culture experiments showed that PP7-induced HSC ferroptosis attenuated macrophage recruitment by regulating inflammation-related genes. HSC-specific inhibition of HIC1 counteracted PP7-induced collagen depletion and HSC ferroptosis in vivo. These findings suggest that PP7 induces HSC ferroptosis through the HIC1/CX3CL1/GPX4 axis.

Pristimerin, which is one of the compounds present in Celastraceae and Hippocrateaceae, has antitumor effects. However, its mechanism of action in esophageal squamous cell carcinoma (ESCC) remains unclear. This study aims to investigate the efficacy and mechanism of pristimerin on ESCC in vitro and in vivo. The inhibitory effect of pristimerin on cell growth was assessed using trypan blue exclusion and colony formation assays. Cell apoptosis was evaluated by flow cytometry. Gene and protein expressions were analyzed through quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry. RNA sequencing (RNA-Seq) was employed to identify significantly differentially expressed genes (DEGs). Cell transfection and RNA interference assays were utilized to examine the role of key proteins in pristimerin?s effect. Xenograft models were established to evaluate the antitumor efficiency of pristimerin in vivo. Pristimerin inhibited cell growth and induced apoptosis in ESCC cells. Upregulation of Noxa was crucial for pristimerin-induced apoptosis. Pristimerin activated the Forkhead box O3a (FoxO3a) signaling pathway and triggered FoxO3a recruitment to the Noxa promoter, leading to Noxa transcription. Blocking FoxO3a reversed pristimerin-induced Noxa upregulation and cell apoptosis. Pristimerin treatment suppressed xenograft tumors in nude mice, but these effects were largely negated in Noxa-KO tumors. Furthermore, the chemosensitization effects of pristimerin in vitro and in vivo were mediated by Noxa. This study demonstrates that pristimerin exerts an antitumor effect on ESCC by inducing AKT/FoxO3a-mediated Noxa upregulation. These findings suggest that pristimerin may serve as a potent anticancer agent for ESCC treatment.
Forkhead Box Protein O3/genetics* ; Humans ; Apoptosis/drug effects* ; Esophageal Squamous Cell Carcinoma/physiopathology* ; Esophageal Neoplasms/physiopathology* ; Pentacyclic Triterpenes ; Animals ; Cell Line, Tumor ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Mice ; Signal Transduction/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Triterpenes/pharmacology* ; Xenograft Model Antitumor Assays ; Mice, Inbred BALB C ; Male ; Gene Expression Regulation, Neoplastic/drug effects*

Objective To explore the feasibility of quantitative EEG parameters for prognostic prediction of patients with severe aneurysmal subarachnoid hemorrhage(SaSAH)90 d after the onset of the disease.Methods Patients with SaSAH admitted to the Neurosurgical Intensive Care Unit(NSICU)of Henan Provincial People's Hospital from September 2022 to September 2023 were prospectively consecutively enrolled,and baseline data were collected,including age,gender,medical history(hypertension,diabetes mellitus,coronary artery disease,and stroke),history of smoking,history of drinking,location of aneurysm(anterior circulation,posterior circulation),surgical modality(craniotomy,interventional surgery,hybrid surgery),Hunt-Hess classification,Glasgow coma scale(GCS)score,acute physiology and chronic health status scoring system Ⅱ(APACHE Ⅱ)score,subarachnoid hemorrhage early brain edema score(SEBES),first randomized blood glucose level after admission to NSICU,lactate level,and duration of NSICU stay.Quantitative EEG monitoring was performed in all patients within 48 h after admission to the NSICU,and amplitude-integrated electroencephalogram(aEEG)upper and lower boundaries,95％spectral edge frequency(SEF95),α change,(δ+θ)to(α+β)power ratio(DTABR),brain symmetry index(BSI),and spectral entropy were collected.Based on modified Rankin scale(mRS)scores 90 d after onset,patients were categorized into good prognosis(mRS score 2 points)and poor prognosis(mRS score 3-6 points)groups.Spearman rank correlation was used to analyze the correlation between quantitative EEG parameters and mRS scores in SaSAH patients.Multifactorial Logistic regression analysis was used to screen for correlates of poor prognosis,and receiver operating characteristic(ROC)curves were plotted to evaluate the efficacy of each index in predicting patients'poor prognosis.Results(1)A total of 72 patients with SaSAH were included,with 47 in the poor prognosis group and 25 in the good prognosis group,and the poor prognosis rate at 90 d after the onset was 65.3％.There was no statistically significant difference between the two groups in terms of gender,age,hypertension,diabetes mellitus,coronary artery disease,history of stroke,history of smoking,history of drinking,location of aneurysm,surgical modality,lactate level,and length of hospitalization in the NSICU(all P＞0.05);the differences between the Hunt-Hess grading,SEBES,and random blood glucose were statistically significant upon comparison(all P＜0.05).Compared with the good prognosis group,the changes of aEEG upper and lower boundary,SEF95,α change and spectral entropy were lower in the poor prognosis group,but DTABR and BSI were higher(all P＜0.05).(2)Spearman rank correlation analysis showed that the upper border of aEEG(r=-0.41,P＜0.01),lower border of aEEG(r=-0.54,P＜0.01),SEF95(r=-0.46,P＜0.01),α change(r=-0.53,P＜0.01)and spectral entropy(r=-0.39,P＜0.01)were negatively correlated with the mRS scores of SaSAH patients,and DTABR(r=0.52,P＜0.01)and BSI(r=0.33,P＜0.01)were positively correlated with poor prognosis of SaSAH patients.(3)The results of multifactorial Logistic regression analysis showed that Hunt-Hess grading(level Ⅳ vs.Ⅲ:OR,1.203,95％CI 1.005-1.441,P=0.044;level V vs.Ⅲ:OR,1.661,95％CI 1.109-2.487,P=0.014),SEBES(OR,1.647,95％CI 1.050-2.586;P=0.030),aEEG lower border(OR,0.687,95％CI 0.496-0.953l;P=0.024),SEF95(OR,0.436,95％CI0.202-0.937;P=0.034),α change(OR,0.368,95％CI0.189-0.717;P=0.003),DTABR(OR,1.324,95％CI 1.064-1.649;P=0.012),and BSI(OR,1.513,95％CI 1.026-2.231;P=0.036)were influencing factors of poor prognosis in SaSAH patients.ROC curve analysis showed that all of the above seven indicators had a certain predictive value for poor prognosis in SaSAH patients,among which the area under the curve of DTABR was the highest as 0.862(95％CI 0.761-0.932),with sensitivity 85.11％and specificity 80.00％.Conclusion Quantitative EEG parameters aEEG lower border,SEF95,α change,DTABR,and BSI may have certain predictive value for the short-term prognosis of SaSAH patients,which needs to be further confirmed in future multi-center large-sample studies.

Objective To construct Raji-Luc lymphoma cells with CD19 knockout using CRISPR/Cas9 technology and preliminarily validate their immune escape ability.Methods PB-CRISPR-CD19 small guide RNA(sgRNA)plasmids was constructed,the optimal sgRNA sequence was screened,and Raji-Luc cells with pCAG-PBase,PB-CD19 sgRNA,and PB-CRISPR-Cas9 were co-transfected.Stable knockout monoclonal cell lines were screened by flow sorting and limit dilution method and the knockout effect was verified through gene sequence testing.The expression of luciferase on the surface of the cell line was detected by microplate reader,CD19 CAR-T and CD38 CAR-T previously constructed in the laboratory were used as effector cells,and the immune escape ability of Raji-Luc CD19 KO cell line was verified by universal luciferase chemiluminescence method.Results The transfection efficiency of Raji-Luc CD19 KO cells prepared by electro transfection was high,and the knockout efficiency of the two monoclonal cells was more than 99%.There was no significant difference in luciferase expression compared to the original Raji-Luc cells,and CD19 CAR-T cells could not be activated to the kill them.Conclusion Successfully constructed Raji-Luc CD19 KO lymphoma cell line.

Objective The scope of related research on ethical conflicts in the interprofessional collaboration in nursing was reviewed,so as to summarize the obstacles and coping strategies that lead to ethical conflicts in interprofessional collaboration and provide references for promoting nurse engagement in interprofessional collaboration.Methods Based on the methodological framework of the scope review,we systematically searched domestic and foreign databases including the Cochrane Library,CINAHL,Embase,PubMed,Web of Science,CNKI,VIP,Wanfang and SinoMed.The time limit for database retrieval was from the establishment of each database to March 2023.The selected studies were summarized and analyzed.Results Totally 13 articles published between 1991 and 2022 were included.The obstacle factors that lead to ethical conflicts in nurse engagement of interprofessional collaboration can be divided into 3 categories,including personal factors(insufficient professional knowledge,differences in professional values),interprofessional factors(imbalanced power between professions,lack of respect and collaboration between cooperators)and environmental factors(insufficient resources and staffing,high-intensity workload,and high-pressure work environment).At the same time,in view of these 3 aspects,it puts forward some countermeasures,such as enhancing professional knowledge,strengthening interprofessional education,improving understanding and cooperation among medical workers in different wards,providing medical practitioners with a team-based,ethical work environment that facilitates interprofessional collaborations and open dialogues.Conclusion It is of great significance for nurses to get involved in interprofessional collaborations,in order to ensure high-quality nursing services.Further studies are needed for the development of education and the core competency framework construction for interprofessional collaborations in nursing.More attention should be paid to develop the organizational atmosphere at the same time,so as to continuously improve nurse'capabilities in interprofessional collaborations.

Objective Based on the Integrated Theory of Health Behavior Change(ITHBC),the influencing factors of home medication safety were explored in patients with chronic heart failure(CHF).Methods This qualitative de-scription,involving a semi-structured in-depth interview of 22 CHF patients based on purposive sampling,was con-ducted from December 2022 to May 2023,at 3 hospitals in Changsha,Hunan.NVivo 11.0 software was used to or-ganize and code data,and content analysis was performed to analyze data.Results Totally 9 generic categories be-longing to 4 categories were extracted.These were knowledge(knowledge of disease and knowledge of medication safety),attitude and belief(attitude towards diseases and medication belief),self-regulation(participation in medica-tion safety self-management and growing through experience),and social facilitation(hospital consultation services,family support and objective situation interference).Conclusion Knowledge,belief,self-regulation and social facili-tation were interrelated to influence medication safety behavior of patients with CHF at home.Medical workers,family members and society should work together to provide medication safety information,create a supportive envi-ronment,focus on improving patients'awareness and ability of self-regulation,strengthen their belief in taking medi-cation,and ultimately ensure the home medication safety for CHF patients.

Objective To understand the current status of nurses'health promotion lifestyle in tertiary comprehensive hospitals,explore the category characteristics of nurses'health promotion lifestyle,and analyze the influencing factors under different categories.Methods From March to April 2023,a multi-stage sampling method was used to select 1326 nurses from 10 tertiary comprehensive hospitals in Hunan Province as the research subjects.A cross-sectional survey was conducted by General Information Questionnaire,Health Promotion Lifestyle Profile Scale,Self-Rated Abilities for Health Practices Scale,Health Behavior Self-Efficacy Assessment Scale,and Nursing Work Environment Scale.Latent profile analysis(LPA)of nurses'health promotion lifestyle was conducted,and the influencing factors of different profiles were explored through univariate analysis and logistic regression analysis.Results A total of 1220 nurses were included,and the score of Health Promotion Lifestyle Profile Scale was(62.61±18.67)points.Nurses'health promotion lifestyle in tertiary comprehensive hospitals can be divided into 3 profiles,namely survival type(25.41％),vitality type(21.97％)and normal type(52.62％).The results of logistic regression analysis showed that coping strategies for stress,non-occupational physical activity,perceived health status,health behavior self-efficacy,and nursing work environment are the influencing factors of nurses'health promotion lifestyle in tertiary comprehensive hospitals(P＜0.05).Conclusion Nurses'health promotion lifestyle in tertiary comprehensive hospitals exhibit significant heterogeneity.It is recommended that nursing managers carry out individualized interventions based on the characteristics of nurses in different categories.Health behavior self-efficacy can be used as the core of intervention to improve nurses'health promotion lifestyles.

Objective To investigate the relationship and potential pathways between metal(loid)exposure and the risk of polycystic ovary syndrome(PCOS)in women of childbearing age. Methods This case-control study included 200 patients with PCOS(cases)and 896 non-PCOS controls with the age of 25-37 years.The concentrations of 29 metal(loid)s in the follicular fluid(FF)and clinical indicators in the serum were measured in all participants.Logistic regression analysis and mediation analysis were conducted to evaluate the associations between metal(loid)exposure and PCOS risk and investigate the possible roles of clinical indicators,respectively. Results Logistic regression analysis revealed an association between high copper levels in FF and increased PCOS risk(highest vs.lowest quartile:adjusted odds ratio=2.94,95%confidence interval:1.83-4.72).A high luteinizing hormone/follicle-stimulating hormone ratio and elevated levels of testosterone and anti-Müllerian hormone(AMH)were strongly associated with increased PCOS risk induced by high copper exposure.The mediation analysis indicated a mediating effect of AMH in the association between copper exposure and PCOS risk. Conclusion Copper may affect PCOS risk through the hypothalamic-pituitary-ovarian axis,mediated by AMH.Copper exposure and internal AMH levels are important indicators for early warning of PCOS development.

Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma(ESCC).Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients.GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog,and TIMER online tool was used to analyze the correlations among TβR1,MMP-2,and MMP-9 in esophageal cancer.Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated.Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age,gender,or tumor differentiation.The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time.Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway,and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated.In cultured ESCC cells,Nanog knockdown significantly decreased the expression of TβR1,p-Smad2/3,MMP-2,and MMP-9 and strongly inhibited cell migration.Conclusion The high expressions of Nanog,MMP-2,and MMP-9,which are positively correlated,are closely related with invasion depth,lymph node metastasis,and prognosis of ESCC.Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway,and its high expression promotes migration of ESCC cells.

Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma(ESCC).Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients.GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog,and TIMER online tool was used to analyze the correlations among TβR1,MMP-2,and MMP-9 in esophageal cancer.Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated.Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age,gender,or tumor differentiation.The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time.Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway,and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated.In cultured ESCC cells,Nanog knockdown significantly decreased the expression of TβR1,p-Smad2/3,MMP-2,and MMP-9 and strongly inhibited cell migration.Conclusion The high expressions of Nanog,MMP-2,and MMP-9,which are positively correlated,are closely related with invasion depth,lymph node metastasis,and prognosis of ESCC.Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway,and its high expression promotes migration of ESCC cells.