ObjectiveTo investigate the protective effect of genistein （Gen） on etoposide-induced chondrocyte senescence and its underlying mechanism. MethodsThe C28/I2 cell line was treated with different concentrations of Gen and etoposide， and the cell viability was detected by the CCK-8 assay. The senescence model of C28/I2 chondrocytes was induced by etoposide， with Gen intervention. Senescence-associated β-galactosidase （SA-β-gal） staining was performed to detect the senescence-positive rate and staining characteristics of chondrocytes. The expressions of peroxiredoxin 6 （Prdx6）， cyclin-dependent kinaseto clarify the functional necessity of Prdx6. ResultsCompared with the etoposide group， the C28/I2 chondrocyte viability significantly increased （P<0.01）， the expression ofsenescence-associated proteins p21 and p16 decreased （P<0.01， P<0.05）， the expression of senescence-associated genes p21 and p16 reduced （both P<0.01）， the fluorescence intensity of senescence-associated proteins p21 and p16 was diminished （P<0.05， P<0.01）， and the proportion of SA-β-gal-positive cells decreased （P<0.01） in the Gen+etoposide group. Compared with the Control group， the expression of Prdx6 was downregulated in the etoposide group （P<0.05）. Compared with the etoposide group， the expression of Prdx6 was upregulated in the Gen+etoposide group （P<0.01）. Compared with the Control group， the GPx activity significantly decreased in the si-Prdx6 group （P<0.01）. Furthermore， compared with the si-Prdx6 group， the GPx activity increased in the si-Prdx6+Gen group （P<0.05）. Molecular docking results revealed that Gen formed hydrogen bond interactions with the active site of Prdx6. After Prdx6 knockdown， the expression of senescence-associated genes p21 and p16 and the fluorescence intensity of senescence-associated proteins p21 and p16 both increased in the Gen+etoposide+si-Prdx6 group （both P<0.01）. ConclusionGen can inhibit etoposide-induced senescence of C28/I2 chondrocytes by upregulating the expression of Prdx6. This study provides potential drug targets and experimental basis for the prevention and treatment of chondrocyte senescence-related diseases.

Background/Aims: Regorafenib is recommended by guidelines and trials as a sequential second-line therapy following progression on first-line sorafenib or lenvatinib in hepatocellular carcinoma (HCC). However, efficacy is limited, highlighting the urgent need to screen suitable patients and develop sensitization strategies. Methods: Acquired sorafenib- or lenvatinib-resistant (SR or LR) HCC cell lines and organoids were established. Genome-wide CRISPR library screen was performed in SR or LR cell strains to identify synthetic lethal targets of regorafenib. RNA-seq and FITC-regorafenib efflux assay were used to elucidate ERBB3-driven downstream signaling. Preclinical mouse models of cell line- and patient-derived xenografts and clinical cohorts of HCC patients were employed to validate the efficacy of ERBB3-guided patient stratification. Results: Screening with CRISPR library, we showed that inhibition of ERBB3 was synthetic lethal with regorafenib in SR or LR cell strains and organoids. Mechanistically, SR or LR triggered feedback activation of ERBB3 signaling and mediated regorafenib efflux via ERBB3-HIF1A-ABCB1 cascade pathway, limiting sensitivity to regorafenib. Moreover, ERBB3-low tumors following SR or LR exhibited significant sensitivity to regorafenib, suggesting its potential as a predictive biomarker to screen optimal candidates for sequential therapy. Seribantumab, an ERBB3-targeting monoclonal antibody, inhibited ERBB3-HIF1A-ABCB1 cascade, and its combination with regorafenib exerted marked synergistic anti-tumor effects on ERBB3-high tumors resistant to sorafenib or lenvatinib both in vitro and in vivo. Conclusions This study revealed that ERBB3 was a key resistance factor driving limited efficacy to sequential regorafenib, but also an effective therapeutic target whose inhibition enhanced regorafenib sensitivity after SR or LR.

Docynia delavayi (Franch.) Schneid. is an economic fruit plant with high medicinal and edible values. The TCP gene family plays a vital role in plant growth and development. To explore the function of the TCP gene family in the growth and development of D. delavayi. In this study, the TCP gene family (DdeTCP) members were identified from the D. delavayi genome and their expression levels at different stages of seed germination and fruit development were analyzed. The results showed that a total of 18 DdeTCP genes were identified from the D. delavayi genome, with uneven location on 11 chromosomes. The phylogenetic tree showed that the 18 DdeTCPs could be classified into class Ⅱ (3) and class Ⅱ (15), suggesting that functional differentiation occurred among the DdeTCP family members. DdeTCP11 highly homologous to AtTCP14 was highly expressed in the early stage of seed germination, which suggested that this gene played a key role in seed germination. In addition, DdeTCP16 in class Ⅱ had a high expression level during the fruit ripening stage, which indicated that it might be related to fruit ripening. The findings lay a foundation for probing into the roles of the DdeTCP gene family in the growth and development of D. delavayi.
Phylogeny ; Gene Expression Regulation, Plant ; Multigene Family ; Genome, Plant/genetics* ; Plant Proteins/genetics* ; Transcription Factors/genetics* ; Germination/genetics* ; Fruit/growth & development* ; Genes, Plant

Objective To analyze the influencing factors of malaria infection of labor service exported to overseas in Langfang City, in order to establish a visualization tool to assist clinicians in predicting the risk of malaria. Methods A total of 4 774 expatriate employees of the Nibei Pipeline Project of the Pipeline Bureau from October 2021 to August 2023 were taken as the subjects, and the gender, age, overseas residence area and Knowledge of malaria controlscores of the study subjects were investigated by questionnaire survey, and the possible risk factors of malaria were screened by logistic regression model. At the same time, the nomogram prediction model was established, and the subjects were divided into the training group and the validation group at a ratio of 2:1, and the area under the curve (ROC) and the decision curve were plotted to evaluate the prediction ability and practicability of the prediction model in this study. Results Among the 4 774 study subjects, 96 cases of malaria occurred, and the detection rate was 2.01%. Junior school （OR=1.723，95% CI:1.361-2.173）， and residence in rural areas（OR=2.091，95%CI:1.760 -3.100）were risk factors (OR>1), while protective measures（OR=0.826，95% CI : 0.781 - 0.901） and high malaria education scores （OR=0.872，95% CI : 0.621 - 0.899）were protective factors.The nomogram prediction model results showed that the area under the curve of the nomogram prediction model in the training group was 0.94 (95% CI : 0.85 - 1.00), while the validation group was 0.93 (95% CI : 0.80 - 1.00). The results of the decision curve showed that when the threshold probability of the population was 0-0.9, the nomogram model was used to predict the risk of malaria occurrence with the highest net income. Conclusion The nomogram prediction model (including gender, education, region, protection and malaria education score) established and validated in this study is of great value for clinicians to screen high-risk patients with malaria.

Objective To investigate the relationship between serum cyclophilin A(CypA),ischemia modi-fied albumin(IMA),galectin-3(Gal-3)levels and oxidative stress and cognitive impairment(CI)in patients with acute cerebral infarction(ACI)complicated with obstructive sleep apnea hypopnea syndrome(OSAHS).Methods A total of 168 patients with ACI complicated with OSAHS who were admitted to the hospital from December 2020 to October 2023 were selected,and the levels of serum CypA,IMA,Gal-3 and oxidative stress indexes[superoxide dismutase(SOD),malondialdehyde(MDA)]in patients with different severity(mild group,moderate group,severe group)were compared.The correlation between serum CypA,IMA,Gal-3 lev-els and oxidative stress indexes were analyzed by Pearson method.The incidence of CI in patients with ACI complicated with OSAHS were statistically analyzed,the levels of serum CypA,IMA and Gal-3 were com-pared between normal cognitive group and CI group,and the risk factors of CI in patients with ACI complicat-ed with OSAHS were analyzed by multivariate Logistic regression model.Results The levels of serum CypA,IMA,Gal-3 and MDA in mild group,moderate group and severe group increased in turn(P<0.05),and ser-um SOD level decreased in turn(P<0.05).Serum CypA,IMA and Gal-3 in ACI patients complicated with OSAHS were negatively correlated with SOD(P<0.05),and positively correlated with MDA(P<0.05).Of 168 ACI patients complicated with OSAHS,79 cases(47.02%)had CI and were included in the CI group.Compared with normal cognitive group,the serum levels of CypA,IMA and Gal-3 in CI group were signifi-cantly increased(P<0.05).Multivariate Logistic regression model analysis showed that apnea hypopnea in-dex(AHI)≥20 times/h,frontal and temporal lobe infarction,elevated CypA level,elevated IMA level,and el-evated Gal-3 level were risk factors for CI in ACI patients complicated with OSAHS(P<0.05).Conclusion The high expression of serum CypA,IMA and Gal-3 in patients with ACI complicated with OS-AHS is significantly correlated with oxidative stress and CI.The increase of serum CypA,IMA and Gal-3 lev-els indicates an increased risk of CI in patients with ACI complicated with OSAHS,and early detection of the three has good clinical value in evaluating the condition of patients with ACI complicated with OSAHS.

Objective To investigate the predictive value of neuregulin 4(Nrg4)combined withγ-aminobutyric acid(GABA)in cognitive dysfunction among patients with severe obstructive sleep apnea-hypopnea syndrome(OSAHS).Methods A total of 169 patients with severe OSAHS were se-lected as study subjects and divided into normal cognitive function group(n=89)and cognitive dys-function group(n=80)based on cognitive function assessment results.General information of the pa-tients was collected,and the levels of Nrg4 and GABA were detected by enzyme-linked immunosor-bent assay(ELISA).Receiver operating characteristic(ROC)curve analysis was used to evaluate the predictive value of Nrg4 and GABA for cognitive dysfunction in OSAHS patients.Results The proportions of patients with a history of hypertension and diabetes,as well as the levels of diastolic blood pressure,total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)were significantly higher in the cognitive dysfunction group than those in the normal cognitive function group(P＜0.05).The levels of Nrg4 and GABA were significantly lower in the cognitive dysfunction group than in the normal cognitive function group(P＜0.05).The Montreal Cognitive Assessment(MoCA)score in the cognitive dys-function group was significantly lower than that in the normal cognitive function group[(12.36±2.35)versus(28.25±1.02),P＜0.05].Multivariate Logistic regression analysis revealed that a history of hypertension and diabetes,diastolic blood pressure,TC,TG,HDL-C,and LDL-C were risk factors for cognitive dysfunction in patients with severe OSAHS(P＜0.05),while Nrg4,GABA,and MoCA scores were protective factors(P＜0.05).ROC curve analysis showed that combined de-tection of Nrg4 and GABA had a higher predictive value for cognitive dysfunction in patients with se-vere OSAHS compared with either marker alone(P＜0.05).Conclusion A history of hyperten-sion and diabetes,diastolic blood pressure,TC,TG,HDL-C,LDL-C,Nrg4,GABA,and MoCA scores are all factors influencing cognitive dysfunction in patients with severe OSAHS.Combined de-tection of Nrg4 and GABA can effectively predict cognitive dysfunction in these patients.

Objective : To explore the effects and mechanisms of Kobophenol A ( KPA) on lipopolysaccharide ( LPS) -induced M1 macrophage polarization，and to provide a theoretical basis for the treatment of inflammatory immune diseases and the development of new drugs． Methods: The M1 macrophage polarization model of RAW264. 7 was established by LPS induction，and the peroxiredoxin 6 ( Prdx6) knockdown model was constructed using the Prdx6 inhibitor MJ33 and Prdx6-siRNA．RAW264. 7 cells，a mouse macrophage cell line，were treated with various concentrations of KPA． Cell viability was assessed using the CCK-8 assay．The expression levels of Prdx6 and M1 macrophage polarization-related proteins，including inducible nitric oxide synthase ( iNOS) and cyclooxygenase-2 ( COX-2) ，were detected by Western blot and immunofluorescence staining．The expression levels of Prdx6 and M1 macrophage polarization-related genes iNOS，interleukin-6 ( IL-6) ，and tumor necrosis factor α ( TNF-α) ，were measured by RT-qPCR. Flow cytometry was employed to detect the expression of cluster of differentiation 86 ( CD86) ，a marker of M1 macrophages． Results: Compared with the LPS-induced M1 macrophage polarization model ， KPA significantly reversed the morphological changes of M1 macrophage polarization in RAW264. 7 macrophages and decreased the expression of M1 macrophage polarization-related proteins iNOS，COX- 2，CD86 and related genes iNOS，IL-6，TNF-α ( all P＜0. 05) ．In addition，LPS significantly downregulated the expression of Prdx6 in RAW264. 7 macrophages，while KPA upregulated the expression of Prdx6．Moreover，treatment with the Prdx6 inhibitor MJ33 significantly upregulated the expression of iNOS，a marker of M1 macrophage polarization，in RAW264. 7 macrophages，whereas treatment with KPA significantly downregulated the expression of iNOS ( all P＜0. 05) ． Conclusion KPA inhibits LPS-induced M1 polarization of RAW264. 7 macrophages by upregulating the expression of Prdx6．

Objective To evaluate the comprehensive value of methicillin-resistant Staphylococcus aureus(MRSA)treatment drugs in artificial joint infections from multiple perspectives and to solve the problem of MRSA infections in artificial joints.Methods Through literature research,relevant literature was retrieved and clinical studies meeting the requirements were selected and summarized.The Analytic Hierarchy Process(AHP)was applied to collect comprehensive clinical evaluation evidence and to conduct evaluations across different dimensions according to evaluation guidelines;the Delphi method combined with AHP was used for expert anonymous questionnaire evaluation,and the data was compared and analyzed.Results A clini-cal comprehensive evaluation index model for the treatment of artificial joint infections was successfully established,and the yaahp analysis software was used to score the comprehensive clinical evaluation evidence in various directions.Treatment drugs,vancomy-cin,daptomycin,and linezolid,at various levels were calculated through the software,and it was concluded that linezolid has the highest clinical comprehensive evaluation score.Conclusion Among the treatment drugs for MRSA infections in artificial joints,linezolid has a higher clinical comprehensive value and can provide a reference for the clinical treatment of MRSA infec-tions in artificial joints.

Objective:To explore the potential profile characteristics of family health in patients with chronic diseases, analyze the influencing factors of different family health categories, and further investigate the relationship between family health categories and the quality of life in patients with chronic diseases, providing a scientific basis for targeted intervention strategies.Methods:This study was a cross-sectional survey. The data for the study were obtained from the Chinese Residents' Psychology and Behavior Survey Research Database. A multistage sampling method was employed to select 1 808 patients with chronic diseases as survey respondents from July to September 2021. Data were collected using the General Information Questionnaire, the Family Health Scale, and the European 5-Dimensional 5-Level Health Scale(EQ-5D-5L). Potential profiles of family health in patients with chronic diseases were identified using latent profile analysis. Univariate analysis and multiple Logistic regression were used to examine influencing factors, and generalized linear regression was performed to analyze the impact of different family health categories on quality of life.Results:A total of 1 808 chronic disease patients were enrolled, comprising 986 males and 822 females, with a age of (55.23 ± 7.02) years. The scores of family health, EQ-5D-5L, EuroQol Visual Analogue Scale were 38(34, 43), 0.94(0.84, 1.00), and 78(63, 87) points. The family health of patients with chronic diseases were categorized into three potential profiles: the low family health group (418 cases accounting for 23.1%), the medium family health group (747 cases accounting for 41.3%), and the high family health group (643 cases accounting for 35.6%). Multivariate Logistic regression analysis showed that family type, marital status, nature of household, education level, number of siblings and type of health insurance were significant factors influencing family health categories ( OR values were 0.464-2.503, all P<0.05). The family health was an important factor influencing quality of life ( χ2 values were 4.05-100.68, all P<0.05). Conclusions:There is significant heterogeneity in the family health of patients with chronic diseases, which can be divided into three distinct categories. Patients with higher family health levels have better quality of life. Medical professionals should develop precise intervention programs tailored to the characteristics of each category to improve family health levels and enhance the quality of life of patients with chronic diseases.

BACKGROUND: For lung transplant recipients (LTRs), rehabilitation management after lung transplantation is a crucial link affecting the recovery of pulmonary function. This study systematically summarizes and generalizes the relevant evidences on postoperative pulmonary function rehabilitation management in LTRs, thereby providing a basis for formulating clinical strategies for postoperative pulmonary function rehabilitation management in this patient population. METHODS: Based on the "6S" evidence model, a systematic search was conducted in domestic and international databases and websites, including UpToDate, BMJ Best Practice, Cochrane Library, Web of Science, China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), Wanfang Database, Guidelines International Network (GIN), and China Yimai Tong Guidelines Network, from the establishment of each database to July 2025. Relevant evidences on postoperative pulmonary function rehabilitation management for LTRs were extracted, and two researchers independently conducted quality assessment, evidence extraction, and integration of the included literature. RESULTS: A total of 18 studies were included, consisting of 3 expert consensuses, 4 systematic reviews/evidence summaries, 4 randomized controlled trials (RCTs), 5 quasi-experimental studies, and 2 cohort studies. A total of 30 pieces of best evidence were summarized, covering 8 themes: rehabilitation assessment, early intervention, exercise training, nutritional management, medication management, respiratory function training, psychological support, and long-term follow-up. CONCLUSIONS Based on evidence-based principles, this study summarizes the best evidence for postoperative pulmonary function rehabilitation training in LTRs and proposes 30 clinically applicable recommendations, which provides a theoretical basis for the clinical implementation of pulmonary function rehabilitation management. Clinical medical and nursing staff should combine specific clinical scenarios and professional judgments to translate the evidence into practice, and provide scientific rehabilitation management and guidance for LTRs.
Humans ; Lung Transplantation/rehabilitation* ; Lung/surgery* ; Transplant Recipients