OBJECTIVE To evaluate the cost-effectiveness of anlotinib combined with penpulimab versus sorafenib as first- line treatment for unresectable hepatocellular carcinoma （uHCC） from the perspective of China’s healthcare system. METHODS Based on data from the APOLLO study， a partitioned survival model was established with a 21-day model cycle to simulate patient survival status over 10 years under anlotinib combined with penpulimab regimen or sorafenib monotherapy. Quality-adjusted life year （QALY） was used as the core evaluation parameter to assess the incremental cost-effectiveness ratio （ICER） of different treatment regimens. Using 3 times China’s per capita gross domestic product （GDP） in 2024 （287 247 yuan/QALY） as the willingness-to-pay （WTP） threshold， cost-utility analysis was performed to evaluate the cost-effectiveness of the treatment regimens. Sensitivity analysis was conducted to validate the robustness of the baseline analysis conclusion. Scenario analysis was performed to consider the impact of anlotinib and penpulimab assistance programs on the results； the price reduction of penpulimab to ensure the cost-effectiveness of the combination regimen was examined under varying WTP thresholds （specifically， 1， 2， and 3 times China’s per capita GDP in 2024）. RESULTS The baseline analysis revealed that the ICER of anlotinib combined with penpulimab regimen relative to the sorafenib regimen was 338 611.20 yuan/QALY， which exceeded the WTP threshold set in this study. Univariate sensitivity analysis indicated that the utility value of progression free survival and penpulimab price significantly influenced the baseline analysis results. Probabilistic sensitivity analysis validated the robustness of the baseline results. The results of scenario analysis indicated that when considering the assistance programs for anlotinib and penpulimab， the obtained ICER values were all below the WTP threshold set at 3 times China’s per capita GDP in 2024. When the price of penpulimab was reduced by 58%， 35%， and 13%， the ICER values were below the WTP threshold， which was 1， 2 and 3 times the per capita GDP of China in 2024， respectively. CONCLUSIONS From the perspective of China’s healthcare system， anlotinib combined with penpulimab regimen for first-line treatment of uHCC lacks cost-effectiveness compared to sorafenib regimen. However， this conclusion would be reversed if the anlotinib and penpulimab assistance programs are taken into account or if the price of penpulimab is reduced by more than 13% and above.

Objective To investigate the current status of family resilience of children with cancer and analyze its influencing factors,to provide a basis for medical staff to formulate intervention plans.Methods Using a convenient sampling method,children with cancer who were hospitalized in 2 tertiary hospitals in Henan Province from January to April 2024 were selected for the survey.A general information questionnaire,family resilience assessment scale,quality of life family version,ZBI caregiver burden interview,and social support rating scale were used to understand the current status of family resilience of children with cancer and to explore the related influencing factors by univariate analysis and multiple stepwise linear regression analysis.Results A total of 280 questionnaires were distributed and 265 valid questionnaires were recovered,with a valid questionnaire recovery rate of 94.64％.The total score of family resilience for primary caregivers of children with cancer was(185.63±30.66).The multiple stepwise linear regression analysis results showed that the children's self-care ability,caregiver's work status,family care burden,and social support level were the influencing factors for family resilience of children with cancer(P＜0.05),and the explanatory variance was 51.3％.Conclusion The family resilience of children with cancer is at a medium level.The worse the children's self-care ability and the heavier the family care burden,the worse the family resilience;the caregiver's work status and good social support are helpful for the family resilience of children with cancer.Healthcare workers should develop intervention programs to address these factors to enhance the family resilience of children with cancer.

Background and Aims:Obstructive jaundice(OJ)caused by common bile duct stones(CBDS)is a major risk factor for acute cholangitis(AC).Early identification of high-risk patients is essential for improving prognosis.Soluble CD163(sCD163)and milk fat globule epidermal growth factor 8(MFG-E8)are associated with inflammatory diseases,but their predictive value for AC in CBDS-related OJ remains unclear.This study aimed to evaluate the predictive significance of serum sCD163 and MFG-E8 levels for AC in patients with CBDS-OJ.Methods:A total of 142 patients with CBDS-OJ admitted from January 2022 to June 2024 were included as the observation group,and 145 healthy individuals undergoing physical examination served as controls.Serum sCD163 and MFG-E8 levels were measured using ELISA.Based on the occurrence of AC within 24 hours after admission,patients with CBDS-OJ were divided into an AC group(n=48)and a non-AC group(n=94).Clinical variables and serological indicators were compared between groups.Multivariate logistic regression was used to identify independent factors associated with AC.Receiver operating characteristic(ROC)curves were generated to assess the predictive performance of sCD163,MFG-E8,and their combination.Results:Compared with the control group,patients with CBDS-OJ showed significantly elevated serum sCD163 levels and decreased MFG-E8 levels(both P<0.05).Within the observation group,the AC group had higher AST,ALT and sCD163 levels and lower MFG-E8 levels than the non-AC group(all P<0.05).Logistic regression identified elevated sCD163 as an independent risk factor(OR=3.478,P<0.001)and reduced MFG-E8 as a protective factor(OR=0.526,P=0.020)for AC.ROC analysis showed AUC values of 0.759 for sCD163,0.787 for MFG-E8,and 0.920 for their combined detection,with the combined model outperforming either marker alone(P<0.001).Conclusion:Serum sCD163 elevation and MFG-E8 reduction are closely associated with the development of AC in patients with CBDS-OJ.Combined detection of sCD163 and MFG-E8 provides superior predictive value and may serve as a useful tool for early risk stratification in clinical practice.

Objective:To explore the experiences of post-traumatic growth in patients with failed assisted reproductive technology (ART), providing a basis for individualized nursing interventions.Methods:This study was a qualitative study. From November to December 2023, purposive sampling was used to select ART failed patients at Reproductive Medicine Center of Affiliated Hospital of Nantong University as participants. Data was collected through semi-structured in-depth interviews, and Colaizzi 7-step analysis method was used to summarize and analyze the data and extract themes.Results:A total of 15 ART failed patients were included, their age was (31.8±3.6) years, years of infertility was (4.7±1.7) years. After analysis, a total of four themes and nine sub-themes were extracted, namely negative emotional experiences in the early stages of trauma (anxiety and depression, psychological stress) ; diversified support systems (family support, social support) ; positive coping styles (positive binary coping between spouses, individual coping) ; post-traumatic growth experiences (mobilizing one's own positive strength, strengthening altruistic awareness, and re-planning the future) .Conclusions:Infertility patients exhibit negative emotions after experiencing ART failure, but also experience post-traumatic growth. Medical and nursing staff should provide targeted guidance based on the psychological state of ART failed patients at different stages to improve their mental health.

Objective:To explore the relationship between mindfulness, optimism, and subjective well-being in post-lung transplantation patients, so as to provide a basis for nursing staff to improve patients' subjective well-being.Methods:This study was a cross-sectional survey. Convenience sampling was used to select 205 post-lung transplantation patients admitted to the First Affiliated Hospital of Guangzhou Medical University from October 2022 to November 2023 for the study. General Information Questionnaire, World Health Organization-Five Well-Being Scale, Mindful Attention Awareness Scale (MAAS) and Life Orientation Test-R (LOT-R) were used to investigate the study participants. Pearson correlation was used to analyze the correlation between subjective well-being and mindfulness and optimism in patients after lung transplantation. AMOS 24.0 software was used to construct a mediating model to analyze the path relationship between mindfulness, optimism and subjective well-being.Results:A total of 205 questionnaires were distributed and 202 valid questionnaires were recovered, with an effective recovery rate of 98.54% (202/205). In 202 patients after lung transplantation, the WHO-5 Well-Being Scale total score, MAAS total score, and LOT-R score were (16.31±4.73), (56.75±9.44), and (18.49±3.85), respectively. Lung transplantation patients' subjective well-being was positively correlated with mindfulness and optimism ( r=0.570, 0.600, both P<0.01). Optimism partially mediated the relationship between mindfulness and subjective well-being, with an effect value of 0.290 and an effect proportion of 52.35% (0.290/0.554) . Conclusions:Mindfulness and optimism are both positively correlated with subjective well-being in post-lung transplantation patients, and mindfulness could also influence subjective well-being through the mediating effect of optimism. Healthcare professionals should fully explore and cultivate positive psychological resources, such as mindfulness, in lung transplant patients, by increasing optimism as the target of intervention, which in turn improves patients' subjective well-being.

Diabetic retinopathy, a prevalent and vision-threatening microvascular complication of diabetes mellitus, is the leading cause of blindness among middle-aged and elderly individuals. Natural diterpenoids isolated from Siegesbeckia pubescens demonstrate potent anti-inflammatory properties. This study aimed to identify novel bioactive diterpenoids from S. pubescens and investigate their effects on oxidative stress and inflammatory responses in diabetic retinopathy, both in vitro and in vivo. Three new ent-pimarane-type diterpenoids (1-3) and six known compounds (4-9) were isolated from the aerial parts of S. pubescens. Their structures were elucidated through spectroscopic data interpretation, and absolute configurations were determined by comparing calculated and experimental electronic circular dichroism (ECD) spectra. Among these compounds, 14β,16-epoxy-ent-3β,15α,19-trihydroxypimar-7-ene (5) exhibited the most potent protective effect against high glucose and interleukin-1β (IL-1β)-stimulated human retinal endothelial cells. Mechanistically, compound 5 promoted endothelial cell survival while ameliorating oxidative stress and inflammatory response in diabetic retinopathy, both in vivo and in vitro. These findings not only suggest that diterpenoids such as compound 5 are important anti-inflammatory constituents in S. pubescens, but also indicate that compound 5 may serve as a lead compound for preventing or treating vascular complications associated with diabetic retinopathy.
Diabetic Retinopathy/metabolism* ; Humans ; Oxidative Stress/drug effects* ; Animals ; Diterpenes, Kaurane/administration & dosage* ; Asteraceae/chemistry* ; Male ; Endothelial Cells/drug effects* ; Abietanes/administration & dosage* ; Molecular Structure ; Mice ; Anti-Inflammatory Agents/chemistry* ; Plant Extracts/chemistry* ; Mice, Inbred C57BL

Background and Aims:Obstructive jaundice(OJ)caused by common bile duct stones(CBDS)is a major risk factor for acute cholangitis(AC).Early identification of high-risk patients is essential for improving prognosis.Soluble CD163(sCD163)and milk fat globule epidermal growth factor 8(MFG-E8)are associated with inflammatory diseases,but their predictive value for AC in CBDS-related OJ remains unclear.This study aimed to evaluate the predictive significance of serum sCD163 and MFG-E8 levels for AC in patients with CBDS-OJ.Methods:A total of 142 patients with CBDS-OJ admitted from January 2022 to June 2024 were included as the observation group,and 145 healthy individuals undergoing physical examination served as controls.Serum sCD163 and MFG-E8 levels were measured using ELISA.Based on the occurrence of AC within 24 hours after admission,patients with CBDS-OJ were divided into an AC group(n=48)and a non-AC group(n=94).Clinical variables and serological indicators were compared between groups.Multivariate logistic regression was used to identify independent factors associated with AC.Receiver operating characteristic(ROC)curves were generated to assess the predictive performance of sCD163,MFG-E8,and their combination.Results:Compared with the control group,patients with CBDS-OJ showed significantly elevated serum sCD163 levels and decreased MFG-E8 levels(both P<0.05).Within the observation group,the AC group had higher AST,ALT and sCD163 levels and lower MFG-E8 levels than the non-AC group(all P<0.05).Logistic regression identified elevated sCD163 as an independent risk factor(OR=3.478,P<0.001)and reduced MFG-E8 as a protective factor(OR=0.526,P=0.020)for AC.ROC analysis showed AUC values of 0.759 for sCD163,0.787 for MFG-E8,and 0.920 for their combined detection,with the combined model outperforming either marker alone(P<0.001).Conclusion:Serum sCD163 elevation and MFG-E8 reduction are closely associated with the development of AC in patients with CBDS-OJ.Combined detection of sCD163 and MFG-E8 provides superior predictive value and may serve as a useful tool for early risk stratification in clinical practice.

Objective: To screen and identify the key active molecules, signaling pathways, and therapeutic targets of Shuxuening (SXN) injection for treating liver cirrhosis (LC) and to evaluate its therapeutic potential using a mouse model. Methods: Target genes of SXN and LC were retrieved from public databases, and enrichment analysis was performed. A protein–protein interaction (PPI) network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), and hub genes were identified using Molecular Complex Detection (MCODE). LC was induced in rats and mice via intraperitoneal injections of diethylnitrosamine and carbon tetrachloride (CCl4) for 12 weeks. Starting at week 7, SXN was administered intraperitoneally to the mice in the treatment group. Serum and liver tissues of the mice were collected for the detection of indicators, pathological staining, and expression analysis of hub targets using quantitative real-time polymerase chain reaction (qRT-PCR). Results: We identified 368 overlapping genes (OLGs) between SXN and LC targets. These OLGs were subsequently used to build a PPI network and to screen for hub genes. Enrichment analysis showed that these genes were associated with cancer-related pathways, including phosphoinositide-3-kinase/Akt and mitogen-activated protein kinase signaling and various cellular processes, such as responses to chemicals and metabolic regulation. In vivo experiments demonstrated that SXN treatment significantly improved liver function and pathology in CCl4-induced LC mice by reducing inflammation and collagen deposition. Furthermore, qRT-PCR demonstrated that SXN regulated the expression of MAPK8, AR and CASP3 in the livers of LC mice. Conclusion This study highlighted the therapeutic effects of SXN in alleviating LC using both bioinformatics and experimental methods. The observed effect was associated with modulation of hub gene expression, particularly MAPK8, and CASP3.

Objective:To analyze the breast cancer-related parameters and the ultrasonic features of positive axillary lymph nodes,to discuss the risk factors for axillary lymphnode metastatic burden,and to provide basis for preoperative evaluation of breast cancer patients.Methods:The ultrasonic and clinicopathological data of 574 breast cancer patients with axillary lymph node metastasis confirmed by surgery and pathology were retrospectively analyzed.According to the status of axillary lymphnode metastasis,the patients were divided into low nodal burden(LNB)group(n=283)and high nodal burden(HNB)group(n=291).The affected side,tumor quadrant,distance to skin,maximum diameter,internal echogenicity,shape,margin,calcification,blood supply,posterior echo,lymphnode long diameter,lymphnode short diameter,lymphnode aspect ratio,number of suspicious metastases,intranodal blood supply,lymphnode hilum morphology,age,pathological type,histological grade,molecular subtype,and the expressions of estrogen receptor(ER),progesterone receptor(PR),Ki-67,human epidermal growth factor receptor 2(HER2),and P53 were compared between two groups.Logistic regression was used to analyze the risk factors for axillary lymph node metastatic burden in the breast cancer patients;receiver operating characteristic(ROC)curve and area under the curve(AUC)were used to evaluate the predictive value.Results:The univariate analysis results showed that there were statistically significant differences in tumor quadrant,distance to skin,molecular subtype,HER2 positive expression,lymphnode long diameter,lymph node short diameter,lymph node aspect ratio,number of suspicious metastases,and lymphnode hilum morphology between two groups(P<0.05).The multivariate Logistic regression analysis results showed that tumor located in the upper outer quadrant(OR=0.648,P=0.021),distance to skin<5 mm(OR=0.283,P=0.016),Luminal A(OR=1.564,P=0.044),lymphnode long diameter≥20 mm(OR=2.050,P<0.01),lymphnode short diameter≥8.6 mm(OR=2.430,P<0.01),lymph node aspect ratio<2(OR=1.585,P<0.01),and indistinct lymphnode hilum structure(OR=2.092,P<0.01)were the independent risk factors for axillary lymphnode metastatic burden.The ROC curve analysis results showed that compared with the ultrasonic features of positive axillary lymph nodes,the AUC of the combination of breast cancer-related parameters and ultrasonic features of positive axillary lymphnodes was larger(Z=2.72,P=0.006 5),and it had higher predictive value for axillary lymphnode metastatic burden.Conclusion:The tumor quadrant,distance to skin,molecular subtype,lymphnode long diameter,lymph node short diameter,lymphnode aspect ratio,and lymphnode hilum structure are the independent risk factors for axillary lymphnode metastatic burden,and they have certain predictive value for axillary lymphnode metastatic burden.

Increasing evidence showed that histone deacetylase 6(HDAC6)dysfunction is directly associated with the onset and progression of various diseases,especially cancers,making the development of HDAC6-targeted anti-tumor agents a research hotspot.In this study,artificial intelligence(AI)technology and molecular simulation strategies were fully integrated to construct an efficient and precise drug screening pipeline,which combined Voting strategy based on compound-protein interaction(CPI)prediction models,cascade molecular docking,and molecular dynamic(MD)simulations.The biological potential of the screened compounds was further evaluated through enzymatic and cellular activity assays.Among the identified compounds,Cmpd.18 exhibited more potent HDAC6 enzyme inhibitory activity(IC50=5.41 nM)than that of tubastatin A(TubA)(IC50=15.11 nM),along with a favorable subtype selectivity profile(selectivity index ≈ 117.23 for HDAC1),which was further verified by the Western blot analysis.Additionally,Cmpd.18 induced G2/M phase arrest and promoted apoptosis in HCT-116 cells,exerting desirable antiproliferative activity(IC50=2.59 μM).Furthermore,based on long-term MD simulation trajectory,the key residues facilitating Cmpd.18's binding were identified by decomposition free energy analysis,thereby elucidating its binding mechanism.Moreover,the representative conformation analysis also indicated that Cmpd.18 could stably bind to the active pocket in an effective conformation,thus demonstrating the potential for in-depth research of the 2-(2-phenoxyethyl)pyridazin-3(2H)-one scaffold.