Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

Objective To establish a mouse model of H1N1 influenza wind-heat syndrome by combining climate intervention with influenza virus nasal drops.Methods Seventy-two BALB/c mice were divided randomly into nine groups:a Control group,wind-heat(FR)groups(FR-3Day,FR-5Day),and Model groups(1LD-3Day,2LD-3Day,3LD-3Day,1LD-5Day,2LD-5Day,2LD-5Day,3LD-5Day)(n=8 mice per group).Mice in the Control group were housed in a normal environment,while mice in the FR and Model groups were kept in wind-heat conditions for 7 d.Mice in the Model groups received nasal PR8 influenza virus infection on the 8th day,and mice in the Control and FR heat groups received equal amounts of physiological saline nasal drops.After virus challenge,each group was housed in a normal environment and samples were taken on days 3 and 5.The appearance of the mice was observed and recorded and the lung index,routine blood parameters,lung tissue pathology,serum interleukin(IL)-6 levels,and virus titers were detected in each group based on their behavioral status,stools,and body temperature.Results After 7 d of wind-heat intervention,mice in the FR groups showed no significant abnormalities in terms of appearance,stools,body temperature,routine blood parameters,or lung tissue pathology compared with the Control group.The appearance,lung index,red blood cell count,hemoglobin,hematocrit,pathological result,and body temperature in the Model groups worsened progressively with increasing time and toxin dosage,while the neutrophil percentage,lymphocyte percentage,virus titer,and serum IL-6 levels peaked on day 3 after viral attack,for the same viral dose,and then decreased slightly on day 5.Conclusions PR8 nasal drops and 7 d of wind-heat climate intervention can be used to establish a mouse model of influenza wind-heat syndrome.

Objective:To explore the relationship between irrational procrastination and compulsory citizenship behavior among clinical nurses,and to investigate the role of psychological entitlement in this relationship.Meth-ods:A sample of 413 clinical nurses from a tertiary hospital was selected for this study.The Irrational Procrastina-tion Scale(IPS),Compulsory Citizenship Behavior Scale(CCBS),and Psychological Entitlement Scale(PES)were used for evaluation.Results:The scores of IPS,CCBS and PES were positively correlated with each other(r=0.53,0.56,0.39,Ps＜0.01).Psychological entitlement partially mediated the relationship between compulsory citi-zenship behavior and irrational procrastination among clinical nurses,with an indirect effect of 0.17,accounting for 13.85％of the total effect.Conclusion:Psychological entitlement plays a partial mediating role in the relationship between compulsory citizenship behavior and irrational procrastination among clinical nurses.

Objective To develop an animal model that replicates the clinical phenotype of severe asthma.Methods Ovalbumin(OVA)combined with IL-33 or varying doses of lipopolysaccharides(LPS)was used to explore the construction of a severe asthma mouse model.Established model animals were assessed for lung function,number of inflammatory cells,and lung tissue pathology were assessed.Expression of key genes associated with severe asthma identified from the GEO database were validated in the new model.Results Compared with OVA alone,OVA combined with IL-33 or 5 μg LPS significantly increased airway resistance and the number of inflammatory cells in bronchoalveolar lavage fluid,and aggravated the pathological damage to lung tissues.The expression patterns of key genes in the newly constructed severe asthma models were consistent with those observed in clinical patients with severe asthma.Conclusions The modeling method of combining OVA with IL-33 or LPS(5 μg)can be used to construct experimentalanimal models of severe asthma.

Objective To develop an animal model that replicates the clinical phenotype of severe asthma.Methods Ovalbumin(OVA)combined with IL-33 or varying doses of lipopolysaccharides(LPS)was used to explore the construction of a severe asthma mouse model.Established model animals were assessed for lung function,number of inflammatory cells,and lung tissue pathology were assessed.Expression of key genes associated with severe asthma identified from the GEO database were validated in the new model.Results Compared with OVA alone,OVA combined with IL-33 or 5 μg LPS significantly increased airway resistance and the number of inflammatory cells in bronchoalveolar lavage fluid,and aggravated the pathological damage to lung tissues.The expression patterns of key genes in the newly constructed severe asthma models were consistent with those observed in clinical patients with severe asthma.Conclusions The modeling method of combining OVA with IL-33 or LPS(5 μg)can be used to construct experimentalanimal models of severe asthma.

Objective To explore the role of histone deacetylase 3(HDAC3)and the intestinal rhythm gene nuclear factor,inter-leukin 3 regulated(NFIL3)and visceral hypersensitivity in mice.Methods C57BL/6J mice were randomly divided into normal group(control group,CON group),sleep deprivation group(SD group),and HDAC3 inhibitor intervention group(SD+RGFP966group).The behaviors of mice were detected by open field test and elevated plus maze test,and visceral sensitivity was evaluated by colonic dila-tion test and pain threshold.The pathological changes of colon tissues in each group were evaluated by hematoxylin-eosin staining,and the expressions of inflammatory factors(IL-17,IL-6)and anti-inflammatory factors(IL-10)in serum were detected by enzyme-linked immunosorbent assay(ELISA).The mRNA expressions of junction proteins(ZO-1,Occludin),inflammatory factors(IL-1 β,IL-6)in colon tissues were determined by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).The protein ex-pressions of NFIL3,HDAC3 and inflammatory factors(TNF-α,IL-1 β)in colon tissues were detected by Western blotting.Results Compared with the CON group,mice in the SD group exhibited anxiety and depression-like behaviors and increased visceral sensitivity(P＜0.05).The hematoxylin-eosin results showed no obvious damage to the structure of colon tissues.The results of Western blot and RT-qPCR showed that the expressions of inflammatory factors in colonic tissue increased(P＜0.05),while the expressions of junction proteins decreased(P＜0.05).The results of Western blot showed that the protein expressions of HDAC3 and NFIL3 increased.Com-pared with the SD group,the anxiety and depression-like behaviors and visceral sensitivity of mice in the SD+RGFP966group were im-proved(P＜0.05),and the expressions of inflammatory factors decreased(P＜0.05),while the expressions of junction proteins in-creased(P＜0.05).The expression of NFIL3decreased after HDAC3 inhibition(P＜0.05).Conclusion HDAC3 inhibitor RGFP966 can improve the visceral hypersensitivity of mice by regulating the intestinal rhythm gene NFIL3.

Objective To explore the role of histone deacetylase 3(HDAC3)and the intestinal rhythm gene nuclear factor,inter-leukin 3 regulated(NFIL3)and visceral hypersensitivity in mice.Methods C57BL/6J mice were randomly divided into normal group(control group,CON group),sleep deprivation group(SD group),and HDAC3 inhibitor intervention group(SD+RGFP966group).The behaviors of mice were detected by open field test and elevated plus maze test,and visceral sensitivity was evaluated by colonic dila-tion test and pain threshold.The pathological changes of colon tissues in each group were evaluated by hematoxylin-eosin staining,and the expressions of inflammatory factors(IL-17,IL-6)and anti-inflammatory factors(IL-10)in serum were detected by enzyme-linked immunosorbent assay(ELISA).The mRNA expressions of junction proteins(ZO-1,Occludin),inflammatory factors(IL-1 β,IL-6)in colon tissues were determined by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).The protein ex-pressions of NFIL3,HDAC3 and inflammatory factors(TNF-α,IL-1 β)in colon tissues were detected by Western blotting.Results Compared with the CON group,mice in the SD group exhibited anxiety and depression-like behaviors and increased visceral sensitivity(P＜0.05).The hematoxylin-eosin results showed no obvious damage to the structure of colon tissues.The results of Western blot and RT-qPCR showed that the expressions of inflammatory factors in colonic tissue increased(P＜0.05),while the expressions of junction proteins decreased(P＜0.05).The results of Western blot showed that the protein expressions of HDAC3 and NFIL3 increased.Com-pared with the SD group,the anxiety and depression-like behaviors and visceral sensitivity of mice in the SD+RGFP966group were im-proved(P＜0.05),and the expressions of inflammatory factors decreased(P＜0.05),while the expressions of junction proteins in-creased(P＜0.05).The expression of NFIL3decreased after HDAC3 inhibition(P＜0.05).Conclusion HDAC3 inhibitor RGFP966 can improve the visceral hypersensitivity of mice by regulating the intestinal rhythm gene NFIL3.

Objective To establish a prediction model for futile recanalization after mechanical thrombectomy(MT)in acute anterior circulation large vessel occlusion(ACLVO)stroke patients based on multimodal imaging features,and to evaluate its predictive performance.Methods Retrospectively enrolled consecutive ACLVO patients who underwent MT with successful recanalization(modified thrombolysis in cerebral infarction[mTICI]grade≥2b)at the Department of Neurology of Fuyang People's Hospital between June 2023 and December 2024.Demographic and clinical data were collected,including age,gender,hypertension,diabetes mellitus,atrial fibrillation,smoking history,alcohol consumption history,National Institutes of Health stroke scale(NIHSS)score upon admission,intravenous thrombolysis,wake-up stroke,onset-to-puncture time(OPT),puncture-to-recanalization time(PRT),occlusion vessel(internal carotid artery,middle cerebral artery),treatment method(suction thrombectomy,stent thrombectomy,suction+stent thrombectomy).All patients underwent pre-procedural CT perfusion(CTP)+CT angiography(CTA)of the head and neck.Imaging parameters included hypoperfusion(defined as time to peak＞6 s)volume(HPV),core infarct(defined as cerebral blood flow＜30%)volume(CIV),mismatch ratio(MMR;HPV/CIV),and Tan collateral score(poor collaterals:0-1 score,good collaterals:2-3 score).Patients were followed up at 90 days post-procedure via outpatient clinic or re-admission.Patients with a modified Rankin scale(mRS)score≤2 were classified into the effective recanalization group,while those with mRS score≥3 were classified into the futile recanalization group.Imaging variables with statistically significant differences between the futile recanalization and effective recanalization groups were included in multivariate Logistic regression analysis to identify independent predictors of futile recanalization and construct a nomogram model.The predictive value of the model was assessed using the receiver operating characteristic(ROC)curve.Model calibration was evaluated using the Hosmer-Lemeshow test(goodness-of-fit defined as P＞0.50).Results(1)A total of 105 ACLVO patients with successful MT recanalization were included(65 males,40 females,mean age[66±11]years,ranged 31～87 years).There were 60 patients in the effective recanalization group and 45 in the futile recanalization group.Compared to the effective recanalization group,the futile recanalization group had significantly higher age([69±11]years vs.[63±11]years,P=0.012),higher proportion of diabetes mellitus(33.33%[15/45]vs.16.67%[10/60],P=0.047),higher pre-treatment NIHSS score([15.51±2.73]vs.[13.25±2.71],P＜0.01),longer OPT([516.40±192.48]min vs.[322.98±171.22]min,P＜0.01)and PRT([94.96±17.37]min vs.[87.58±15.99]min,P=0.026),larger CIV([74.00±12.76]ml vs.[24.28±14.72]ml,P＜0.01)and HPV([121.43±22.21]ml vs.[91.62±11.34]ml,P＜0.01),smaller MMR([1.65±0.15]vs.[9.42±1.91],P＜0.01),higher 90-day mRS score([3.60±0.54]score vs.[1.22±0.83]score,P＜0.01),and a significantly different distribution of Tan collateral scores(P＜0.01).(2)Multivariate Logistic regression analysis was performed with futile recanalization as the dependent variable,identified the following independent predictors of futile recanalization:HPV(OR,2.042,95%CI 1.296-3.218,P=0.002),CIV(OR,2.373,95%CI 1.315-4.280,P=0.004),MMR(OR,1.758,95%CI 1.135-2.721,P=0.011),and Tan collateral score(OR,5.166,95%CI 2.100-12.651,P＜0.01).(3)A nomogram prediction model for futile recanalization after MT in ACLVO stroke was constructed based on the four imaging parameters as aforementioned.ROC curve analysis demonstrated that the area under the curve for this model in predicting futile recanalization after MT was 0.846(95%CI 0.739-0.912),with a sensitivity of 0.844 and a specificity of 0.817.The calibration curve and the Hosmer-Lemeshow test indicated the goodness-of-fit was high(P=0.617),and the overall stability of the model was good.Conclusion The predictive model for futile recanalization after MT for acute ACLVO constructed base on HPV,CIV,MMR and Tan collateral score facilitates the identification patients with high-risk of futile recanalization.

Objective To establish a prediction model for futile recanalization after mechanical thrombectomy(MT)in acute anterior circulation large vessel occlusion(ACLVO)stroke patients based on multimodal imaging features,and to evaluate its predictive performance.Methods Retrospectively enrolled consecutive ACLVO patients who underwent MT with successful recanalization(modified thrombolysis in cerebral infarction[mTICI]grade≥2b)at the Department of Neurology of Fuyang People's Hospital between June 2023 and December 2024.Demographic and clinical data were collected,including age,gender,hypertension,diabetes mellitus,atrial fibrillation,smoking history,alcohol consumption history,National Institutes of Health stroke scale(NIHSS)score upon admission,intravenous thrombolysis,wake-up stroke,onset-to-puncture time(OPT),puncture-to-recanalization time(PRT),occlusion vessel(internal carotid artery,middle cerebral artery),treatment method(suction thrombectomy,stent thrombectomy,suction+stent thrombectomy).All patients underwent pre-procedural CT perfusion(CTP)+CT angiography(CTA)of the head and neck.Imaging parameters included hypoperfusion(defined as time to peak＞6 s)volume(HPV),core infarct(defined as cerebral blood flow＜30%)volume(CIV),mismatch ratio(MMR;HPV/CIV),and Tan collateral score(poor collaterals:0-1 score,good collaterals:2-3 score).Patients were followed up at 90 days post-procedure via outpatient clinic or re-admission.Patients with a modified Rankin scale(mRS)score≤2 were classified into the effective recanalization group,while those with mRS score≥3 were classified into the futile recanalization group.Imaging variables with statistically significant differences between the futile recanalization and effective recanalization groups were included in multivariate Logistic regression analysis to identify independent predictors of futile recanalization and construct a nomogram model.The predictive value of the model was assessed using the receiver operating characteristic(ROC)curve.Model calibration was evaluated using the Hosmer-Lemeshow test(goodness-of-fit defined as P＞0.50).Results(1)A total of 105 ACLVO patients with successful MT recanalization were included(65 males,40 females,mean age[66±11]years,ranged 31～87 years).There were 60 patients in the effective recanalization group and 45 in the futile recanalization group.Compared to the effective recanalization group,the futile recanalization group had significantly higher age([69±11]years vs.[63±11]years,P=0.012),higher proportion of diabetes mellitus(33.33%[15/45]vs.16.67%[10/60],P=0.047),higher pre-treatment NIHSS score([15.51±2.73]vs.[13.25±2.71],P＜0.01),longer OPT([516.40±192.48]min vs.[322.98±171.22]min,P＜0.01)and PRT([94.96±17.37]min vs.[87.58±15.99]min,P=0.026),larger CIV([74.00±12.76]ml vs.[24.28±14.72]ml,P＜0.01)and HPV([121.43±22.21]ml vs.[91.62±11.34]ml,P＜0.01),smaller MMR([1.65±0.15]vs.[9.42±1.91],P＜0.01),higher 90-day mRS score([3.60±0.54]score vs.[1.22±0.83]score,P＜0.01),and a significantly different distribution of Tan collateral scores(P＜0.01).(2)Multivariate Logistic regression analysis was performed with futile recanalization as the dependent variable,identified the following independent predictors of futile recanalization:HPV(OR,2.042,95%CI 1.296-3.218,P=0.002),CIV(OR,2.373,95%CI 1.315-4.280,P=0.004),MMR(OR,1.758,95%CI 1.135-2.721,P=0.011),and Tan collateral score(OR,5.166,95%CI 2.100-12.651,P＜0.01).(3)A nomogram prediction model for futile recanalization after MT in ACLVO stroke was constructed based on the four imaging parameters as aforementioned.ROC curve analysis demonstrated that the area under the curve for this model in predicting futile recanalization after MT was 0.846(95%CI 0.739-0.912),with a sensitivity of 0.844 and a specificity of 0.817.The calibration curve and the Hosmer-Lemeshow test indicated the goodness-of-fit was high(P=0.617),and the overall stability of the model was good.Conclusion The predictive model for futile recanalization after MT for acute ACLVO constructed base on HPV,CIV,MMR and Tan collateral score facilitates the identification patients with high-risk of futile recanalization.

Objective:This study aimed to summarize and analyze the preliminary application experience of a novel pressurized intraperitoneal aerosol chemotherapy (PIPAC) device in patients with peritoneal metastases of gastrointestinal malignancies.Methods:In this descriptive case series study, four patients with pathologically confirmed peritoneal metastatic gastrointestinal malignancies were enrolled, receiving PIPAC treatment at Guangdong Provincial People's Hospital from December 2024 to February 2025. The PIPAC treatment was performed five times on these patients . Key procedural steps included equipment preparation, operation platform construction, cytologic examination of ascites, Peritoneal Cancer Index (PCI) scoring, biopsy of peritoneal metastases, drug preparation, connection and testing of the PIPAC device, PIPAC treatment, and aerosol evacuation. Preoperative and postoperative clinical data were collected and analyzed to assess the safety and feasibility of PIPAC treatment.Results:3 males and 1 female patients were enrolled; median age was 57 (range, 36-70) years old; median body mass index was 22.5 (range, 18.0-24.6) kg/m2, and the preoperative Eastern Cooperative Oncology Group (ECOG) score was 1 for all cases. Four patients successfully completed the five PIPAC treatments without any intraoperative adverse events. The PIPAC treatment time ranged from 34 minutes to 36 minutes, with a median preoperative PCI score of 18 (range, 5-25). The average Peritoneal Regression Grading Score (PRGS) before the first and second PIPAC treatments were 2.1±0.8 and 1.7±0.6, respectively. The median Visual Analog Scale (VAS) scores for pain on postoperative days 1, 2, and 3 were 2 (range, 2-4), 1 (range, 0-2), and 1 (range, 0-2), respectively. All patients resumed the oral intake and ambulation on the first postoperative day, with a postoperative hospital stay of 3 days. No postoperative complications or perioperative death occurred.Conclusion:The preliminary study results indicate that the use of the novel PIPAC device for the treatment of peritoneal metastases of gastrointestinal malignant tumors is safe and feasible.