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.

Objectives:To summarize the characteristics of Fabry′s disease with cardiac involvement.Methods:This was a single-center, cross-sectional, retrospective study. Patients with Fabry disease who were admitted to Zhongda Hospital Affiliated to Southeast University from January 2022 to March 2023 were included. Clinical data, laboratory results, electrocardiogram, echocardiography and cardiac magnetic resonance findings of enrolled patients were collected. Clinical presentations and imaging features of patients with Fabry′s disease with cardiac involvement were summarized and analyzed.Results:A total of 17 patients from 8 families were included, with 9 males and diagnosis age of (44.35±13.72) years. Cardiac involvement and other organ involvement were presented in all patients and the heart was the most vulnerable organ (17/17). 24 h electrocardiogram showed frequent sinus arrhythmia in 3 patients. Echocardiography showed reduced left ventricular ejection fraction in 1 patient, myocardial hypertrophy in 13 patients, and left ventricular wall thickness ≥13 mm in 10 patients. Mitral regurgitation was observed in 11 patients and tricuspid regurgitation in 12 patients. Two patients underwent two-dimensional speckle tracking echocardiography, both revealing reduced regional longitudinal strain of the left ventricle, primarily in the basal segments. Cardiac magnetic resonance showed reduced left ventricular ejection fraction in 2 patients, myocardial hypertrophy in 16 patients, and left ventricular wall thickness≥13 mm in 14 patients. T1 value was reduced in 16 patients, with late gadolinium enhancement observed in 9 patients and “pseudo-normalization” of T1 values in 1 patient. The most susceptible target organ besides the heart was the kidneys (14/17), followed by the central nervous system (9/17). Additional findings inclucling cutaneous angiokeratoma in 4 patients, peripheral neuropathy with burning pain and hypohidrosis or hyperhidrosis in 6 patients, and corneal vortex opacities in 2 patients.Conclusion:The main manifestations of cardiac involvement in Fabry′s disease are decreased cardiac function, left ventricular hypertrophy and myocardial fibrosis. Advanced imaging techniques such as two-dimensional speckle tracking, T1 Mapping, and late gadolinium enhancement are useful in detecting myocardial pathological changes of Fabry′s disease.

Objective To systematically analyze the influencing factors of chronic liver disease patients' perception of symptoms based on the Andersen model,and to provide methodological reference for the study in the prevention and treatment of chronic diseases.Methods Based on the predisposing factors,enabling factors,demand factors,health behaviors,and health outcomes of the Andersen model,an influencing factor model was constructed.A community cluster convenience sample survey method was used to conduct a questionnaire star survey on chronic liver disease patients in multiple communities in Liwan,Guangzhou from November 2018 to March 2020.Univariate Mann-Whitney U test,Kruskal-Wallis H test,Spearman correlation analysis,and multivariate generalized linear hierarchical model analysis were performed.Results A total of 494 valid questionnaires were collected,and the median score for the patients' perception of the symptoms was 32(26,42)points.For the predisposing factors:age,education level,overtime status,and formal medical treatment;for the enabling factors:income and expenditure situation,personal history of hyperlipidemia;for the demand factors:cognition of medical and nursing integration,regular reexamination;and for the health behaviors:daily water intake,use of digital devices,and exercise and health care were all influencing factors(P＜0.05).Comparing the hierarchical models,health behaviors had the highest impact on the perception of the symptoms in chronic liver disease patients,followed by enabling factors,and demand factors had the lowest impact.Conclusion Medical staff should focus on the health behaviors of chronic liver disease patients with different predisposing factors,optimize the enabling factors,strengthen the guidance and intervention of demand factors,and provide comprehensive and personalized medical care plans.

ObjectiveTo investigate the mechanism by which Huanglian Jiedutang （HLJDT） inhibits pyroptosis and neuroinflammation in Alzheimer's disease （AD） mice via the NOD-like receptor protein 3 （NLRP3）/cysteinyl aspartate-specific protease-1 （Caspase）-1/gasdermin D （GSDMD） pathway. MethodsThirty APP/PS1 double transgenic mice were randomly and evenly divided into the model group （model group）， the positive control group （Donepezil group， 0.65 mg·kg^-1）， and the HLJDT treatment group （HLJDT group， 5.2 g·kg^-1）. Ten C57BL/6 mice were assigned to the blank control group （control group）. The Morris water maze and novel object recognition tests were used to evaluate learning and memory abilities. Nissl staining was employed to observe the morphology， quantity， and distribution of neurons in the hippocampal region. Golgi staining was used to examine the morphology and density of neuronal dendritic spines in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was performed to detect the mRNA expression of neuroinflammation-related factors and genes in the NLRP3/Caspase-1/GSDMD pyroptosis pathway in the hippocampus. Western blot was used to detect the expression of postsynaptic density protein 95 （PSD95）， amyloid precursor protein （APP）， inflammatory factors including nuclear factor-κB （NF-κB）， phosphorylated NF-κB （p-NF-κB）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， as well as pyroptosis pathway-related proteins including NLRP3， Caspase-1， GSDMD， and GSDMD-N. ResultsCompared with the control group， the model group exhibited significantly decreased learning and memory abilities （P<0.01）， reduced numbers of neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region （P<0.01）， and significantly increased hippocampal mRNA expression levels of NLRP3， Caspase-1， GSDMD， NF-κB， TNF-α， IL-1β， and IL-18 （P<0.01）. Protein levels of PSD95 were markedly decreased， while the expression levels of NLRP3， Caspase-1， GSDMD， p-NF-κB/NF-κB， TNF-α， IL-1β， and APP were significantly elevated （P<0.01）. Compared with the model group， both the Donepezil and HLJDT groups showed significantly improved learning and memory abilities （P<0.05， P<0.01）， increased numbers of hippocampal neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region （P<0.01）， and significantly decreased hippocampal mRNA expression levels of NLRP3， Caspase-1， GSDMD， NF-κB， TNF-α， IL-1β， and IL-18 （P<0.05， P<0.01）. Protein levels of NLRP3， Caspase-1， GSDMD， p-NF-κB/NF-κB， TNF-α， IL-1β， and APP were significantly downregulated， while PSD95 expression was significantly upregulated （P<0.05， P<0.01）. There was no statistically significant difference in GSDMD-N levels in the Donepezil group， while GSDMD-N expression was significantly decreased in the HLJDT group （P<0.05）. ConclusionThis study confirms that HLJDT can improve learning and memory abilities in APP/PS1 double transgenic mice， and attenuate neuronal loss and synaptic damage， possibly through inhibition of pyroptosis via the NLRP3/Caspase-1/GSDMD pathway.

ObjectiveTo investigate the mechanism by which Huanglian Jiedutang （HLJDT） inhibits pyroptosis and neuroinflammation in Alzheimer's disease （AD） mice via the NOD-like receptor protein 3 （NLRP3）/cysteinyl aspartate-specific protease-1 （Caspase）-1/gasdermin D （GSDMD） pathway. MethodsThirty APP/PS1 double transgenic mice were randomly and evenly divided into the model group （model group）， the positive control group （Donepezil group， 0.65 mg·kg^-1）， and the HLJDT treatment group （HLJDT group， 5.2 g·kg^-1）. Ten C57BL/6 mice were assigned to the blank control group （control group）. The Morris water maze and novel object recognition tests were used to evaluate learning and memory abilities. Nissl staining was employed to observe the morphology， quantity， and distribution of neurons in the hippocampal region. Golgi staining was used to examine the morphology and density of neuronal dendritic spines in the hippocampus. Real-time quantitative polymerase chain reaction （Real-time PCR） was performed to detect the mRNA expression of neuroinflammation-related factors and genes in the NLRP3/Caspase-1/GSDMD pyroptosis pathway in the hippocampus. Western blot was used to detect the expression of postsynaptic density protein 95 （PSD95）， amyloid precursor protein （APP）， inflammatory factors including nuclear factor-κB （NF-κB）， phosphorylated NF-κB （p-NF-κB）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， as well as pyroptosis pathway-related proteins including NLRP3， Caspase-1， GSDMD， and GSDMD-N. ResultsCompared with the control group， the model group exhibited significantly decreased learning and memory abilities （P<0.01）， reduced numbers of neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region （P<0.01）， and significantly increased hippocampal mRNA expression levels of NLRP3， Caspase-1， GSDMD， NF-κB， TNF-α， IL-1β， and IL-18 （P<0.01）. Protein levels of PSD95 were markedly decreased， while the expression levels of NLRP3， Caspase-1， GSDMD， p-NF-κB/NF-κB， TNF-α， IL-1β， and APP were significantly elevated （P<0.01）. Compared with the model group， both the Donepezil and HLJDT groups showed significantly improved learning and memory abilities （P<0.05， P<0.01）， increased numbers of hippocampal neurons in the hippocampal CA3 region and dendritic spines in the hippocampal CA1 region （P<0.01）， and significantly decreased hippocampal mRNA expression levels of NLRP3， Caspase-1， GSDMD， NF-κB， TNF-α， IL-1β， and IL-18 （P<0.05， P<0.01）. Protein levels of NLRP3， Caspase-1， GSDMD， p-NF-κB/NF-κB， TNF-α， IL-1β， and APP were significantly downregulated， while PSD95 expression was significantly upregulated （P<0.05， P<0.01）. There was no statistically significant difference in GSDMD-N levels in the Donepezil group， while GSDMD-N expression was significantly decreased in the HLJDT group （P<0.05）. ConclusionThis study confirms that HLJDT can improve learning and memory abilities in APP/PS1 double transgenic mice， and attenuate neuronal loss and synaptic damage， possibly through inhibition of pyroptosis via the NLRP3/Caspase-1/GSDMD pathway.

Objective:To explore the molecular mechanism of TCM compound Shengxue Tongbian Granules in improving intestinal injury in septic rats through bioinformatics and experimental validation methods.Methods:The GSE131761 gene set was processed by bioinformatics to screen differential genes, then weighted gene co-expression network analysis (WGCNA) was applied to screen modular genes. The intersection of modular genes and differential genes was taken, and finally, the least absolute shrinkage and selection operator (LASSO) technique was applied to further obtain the key targets of sepsis, which was validated by experiments. Totally 72 SD rats were divided into sham-operation group, model group, dexamethasone group (0.15 mg/kg), Shengxue Tongbian Granules low- (0.3 g/kg), medium- (0.6 g/kg), and high-dosage (1.2 g/kg) groups, with 12 rats in each group. Corresponding drug interventions were administered to each treatment group before and 12 hours after modeling. The sham-operation group and the model group were gavaged daily with equal amounts of saline. Samples were collected after 24 hours. HE staining was used to detect the pathological morphology of intestinal tissues in each group of rats; ELISA was used to detect the levels of TNF-α, diamine oxidase (DAO), IL-6, IL-10, and myeloperoxidase (MPO) in rat serum. Immunohistochemistry was used to detect the protein expressions of MPO and neutrophil elastase (NE/LANE) in intestinal tissue, and Western blot was used to detect the protein expression of peptidyl arginine deaminase (PAD4) in intestinal tissue.Results:Seven final key genes related to sepsis were selected, namely ANXA3, CYP1B1, FCAR, LILRA5, PADI4, NOV, and S100A12. Experimental results showed that drug administration alleviated intestinal injury; compared with the model group, the levels of TNF-α, IL-6, MPO, and DAO decreased in the Shengxue Tongbian Granules high-dosage group ( P<0.05), the levels of ELANE and MPO were reduced in Shengxue Tongbian Granules low-, medium-, and high-dosage groups ( P<0.05), and PAD4 expression was reduced in the Shengxue Tongbian Granules high-dosage group ( P<0.05). Conclusion:Shengxue Tongbian Granules can improve the intestinal injury of septic rats, and the mechanism may be related to the inhibition of PAD4-mediated formation of NETs and the improvement of inflammatory response.

Objective To systematically analyze the influencing factors of chronic liver disease patients' perception of symptoms based on the Andersen model,and to provide methodological reference for the study in the prevention and treatment of chronic diseases.Methods Based on the predisposing factors,enabling factors,demand factors,health behaviors,and health outcomes of the Andersen model,an influencing factor model was constructed.A community cluster convenience sample survey method was used to conduct a questionnaire star survey on chronic liver disease patients in multiple communities in Liwan,Guangzhou from November 2018 to March 2020.Univariate Mann-Whitney U test,Kruskal-Wallis H test,Spearman correlation analysis,and multivariate generalized linear hierarchical model analysis were performed.Results A total of 494 valid questionnaires were collected,and the median score for the patients' perception of the symptoms was 32(26,42)points.For the predisposing factors:age,education level,overtime status,and formal medical treatment;for the enabling factors:income and expenditure situation,personal history of hyperlipidemia;for the demand factors:cognition of medical and nursing integration,regular reexamination;and for the health behaviors:daily water intake,use of digital devices,and exercise and health care were all influencing factors(P＜0.05).Comparing the hierarchical models,health behaviors had the highest impact on the perception of the symptoms in chronic liver disease patients,followed by enabling factors,and demand factors had the lowest impact.Conclusion Medical staff should focus on the health behaviors of chronic liver disease patients with different predisposing factors,optimize the enabling factors,strengthen the guidance and intervention of demand factors,and provide comprehensive and personalized medical care plans.

Objectives:To summarize the characteristics of Fabry′s disease with cardiac involvement.Methods:This was a single-center, cross-sectional, retrospective study. Patients with Fabry disease who were admitted to Zhongda Hospital Affiliated to Southeast University from January 2022 to March 2023 were included. Clinical data, laboratory results, electrocardiogram, echocardiography and cardiac magnetic resonance findings of enrolled patients were collected. Clinical presentations and imaging features of patients with Fabry′s disease with cardiac involvement were summarized and analyzed.Results:A total of 17 patients from 8 families were included, with 9 males and diagnosis age of (44.35±13.72) years. Cardiac involvement and other organ involvement were presented in all patients and the heart was the most vulnerable organ (17/17). 24 h electrocardiogram showed frequent sinus arrhythmia in 3 patients. Echocardiography showed reduced left ventricular ejection fraction in 1 patient, myocardial hypertrophy in 13 patients, and left ventricular wall thickness ≥13 mm in 10 patients. Mitral regurgitation was observed in 11 patients and tricuspid regurgitation in 12 patients. Two patients underwent two-dimensional speckle tracking echocardiography, both revealing reduced regional longitudinal strain of the left ventricle, primarily in the basal segments. Cardiac magnetic resonance showed reduced left ventricular ejection fraction in 2 patients, myocardial hypertrophy in 16 patients, and left ventricular wall thickness≥13 mm in 14 patients. T1 value was reduced in 16 patients, with late gadolinium enhancement observed in 9 patients and “pseudo-normalization” of T1 values in 1 patient. The most susceptible target organ besides the heart was the kidneys (14/17), followed by the central nervous system (9/17). Additional findings inclucling cutaneous angiokeratoma in 4 patients, peripheral neuropathy with burning pain and hypohidrosis or hyperhidrosis in 6 patients, and corneal vortex opacities in 2 patients.Conclusion:The main manifestations of cardiac involvement in Fabry′s disease are decreased cardiac function, left ventricular hypertrophy and myocardial fibrosis. Advanced imaging techniques such as two-dimensional speckle tracking, T1 Mapping, and late gadolinium enhancement are useful in detecting myocardial pathological changes of Fabry′s disease.

Objective To investigate the relationship between serum solute carrier family 7 member 11(SLC7A11)and Janus kinase 2(JAK2)levels and the severity and prognosis of acute non-variceal upper gas-trointestinal bleeding(ANVUGIB).Methods A total of 108 patients with ANVUGIB who were treated in the hospital from April 2019 to April 2023 were selected and divided into severe group(31 cases),moderate group(44 cases)and mild group(33 cases)according to the severity of ANVUGIB.The patients were divided into poor prognosis group(41 cases)and good prognosis group(67 cases)according to their prognosis.An-other 50 healthy volunteers who underwent physical examination in the hospital during the same period were selected as the control group.Serum SLC7A11 and JAK2 levels were detected by enzyme-linked immunosor-bent assay.Spearman correlation analysis was used to analyze the correlation between serum SLC7A11 and JAK2 levels and Framingham risk score(FRS)and Glasweg-Blatchford bleeding score(GBS).Multivariate Logistic regression was used to analyze the influencing factors of poor prognosis in patients with ANVUGIB.Receiver operating characteristic(ROC)curve was used to analyze the predictive value of serum SLC7A11 and JAK2 for poor prognosis in patients with ANVUGIB.Results The serum SLC7A11 level was significantly lower and the serum JAK2 level was significantly higher in the three groups of ANVUGIB patients than in the control group(all P＜0.05).As the severity of the disease increased,the serum SLC7A11 level gradually de-creased,and the serum JAK2 level,FRS and GBS scores gradually increased(all P＜0.05).In ANVUGIB pa-tients,serum SLC7A11 level was negatively correlated with FRS and GBS scores,and serum JAK2 level was positively correlated with FRS and GBS scores(all P＜0.05).Compared with the good prognosis group,the poor prognosis group had significantly higher proportion of patients with bleeding volume＞400 mL,red blood cell distribution width,FRS score,GBS score,and JAK2 level,and significantly lower levels of hemoglo-bin and SLC7A11(P＜0.05).Bleeding volume＞400 mL and elevated JAK2 level were risk factors for poor prognosis in ANVUGIB patients,while elevated SLC7A11 level was a protective factor(all P＜0.05).The ar-ea under the curve of combined SLC7A11 and JAK2 in predicting poor prognosis of ANVUGIB patients was better than that of each index alone(Zcombination-SLC7A11=3.086,Zcombination JAK2=2.330,P=0.020,0.030).Conclu-sion The decrease of SLC7A11 level and increase of JAK2 level in patients with ANVUGIB can effectively e-valuate the severity and prognosis of patients,and the combination of the two can predict the prognosis of pa-tients with ANVUGIB.

With the maturation of proteomics technologies in recent years, proteomics has made significant achievements in early detection of major diseases, disease classification, drug target discovery, and other fields. To explore the important role of proteomics, especially proteomics-based cutting-edge lifeomics technologies, in promoting the development of precision laboratory medicine and to discuss the opportunities and challenges faced during the clinical translation of innovative outcomes, the National Center for Protein Sciences-Beijing invited renowned experts and scholars in laboratory medicine, lifeomics, and precision medicine. The discussions revolved around the collaborative development of laboratory medicine and lifeomics, the future trends of new technologies in clinical laboratory testing, the innovation and development of lifeomics in laboratory medicine, the translational application of proteomics technologies in laboratory medicine, and the opportunities and challenges in the industrialization of proteomics achievements. All participants agreed that proteomics provides new directions and opportunities for precision diagnosis and treatment of diseases. However, close collaboration between academia, hospitals and industry is required. Additionally, challenges such as clinical applicability of equipment, standardization of detection methods and data, cost and quality control, talent cultivation, and the industrialization pathway need to be addressed.