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 explore the differences in the clinical laboratory test indexes between the patients with two different TCM syndrome types of eczema(dampness-heat infiltration type and non-dampness-heat infiltration type)and observe the distribution and drug resistance rate of pathogens isolated from the skin lesions so as to pro-vide bases for syndrome differentiation and reasonable use of antibiotics.METHODS A total of 180 patients with eczema who were positive for bacterial culture of skin secretions and were treated in Beijing Hospital of Traditional Chinese Medicine from Jan.2021 to Dec.2023 were enrolled in the study and were divided into the dampness-heat infiltration group with 134 cases and the non-dampness-heat infiltration group with 46 cases.The data of clini-cal laboratory test indexes were collected from the two groups of patients,the secretion specimens were sampled from the skin lesion sites,the isolated pathogens were identified by VITEK 2 Compact automatic microorganism analysis system,and the drug susceptibility testing was performed.RESULTS The direct bilirubin level of the dampness-heat infiltration group was(3.99±1.62)umol/L,higher than(3.46±1.12)umol/L of the non-damp-ness-heat infiltration group(P＜0.05),but both were in the normal range;there were no significant differences in other test indexes between the two groups.Totally 180 strains of pathogens were isolated from the 180 patients with eczema,156(86.67％)of which were gram-positive bacteria;Staphylococcus aureus(98 strains),Staphy-lococcus epidermidis(29 strains)and Staphylococcus haemolyticus(15 strains)were the predominant species of the gram-positive bacteria.The gram-negative bacteria accounted for 12.22％(22 strains).The drug resistance rate of the S.aureus strains to penicillin was up to 82.65％,and the isolation rate of methicillin-resistant Staphy-lococcus aureus(MRSA)was 12.24％(12/98);the drug resistance rates of the S.epidermidis strains to penicil-lin and erythromycin were 75.86％,and the drug resistance rate of the S.haemolyticus strains to erythromycin was 100.00％.CONCLUSIONS The gram-positive bacteria(dominated by the S.aureus)are dominant among the pathogens isolated from the skin lesion specimens of the eczema patients and are highly resistant to penicillin and erythromycin.The isolation rate of MRSA is relatuvely low.There is limited clinical significant difference in the direct bilirubin between the two groups.It is necessary to further explore more reliable indexes for syndrome dif-ferentiation.

Objective:To observe the effects of moxibustion at Shenshu(BL23)and Zusanli(ST36)on Toll-like receptor 4(TLR4)-myeloid differentiation factor 88(Myd88)signaling pathway-mediated inflammatory factors in the synovial tissue of ankle joints of rats with rheumatoid arthritis(RA),and to explore the molecular and biological mechanisms underlying the anti-inflammatory and analgesic effects.Methods:A total of 24 male Sprague-Dawley(SD)rats were randomly divided into a normal group,a model group,and a moxibustion group,with 8 rats in each group.The RA model was established with exposure to wind,cold,and damp environmental factors,along with Freund's complete adjuvant.After three days of modeling,mild moxibustion was applied to bilateral Shenshu(BL23)and Zusanli(ST36)in the moxibustion group using moxa sticks of 0.9 cm in diameter for 30 min each time,once a day for 14 d.Structural changes in the synovial tissue and cells were then observed using hematoxylin-eosin staining and transmission electron microscopy,while immunohistochemistry analysis was used to detect tumor necrosis factor(TNF)-α,interleukin(IL)-17,IL-1β,and IL-6 levels.Moreover,the protein expression levels of Myd88,TLR4,and transient potential receptor vanilloid type 1(TRPV1)in the synovial tissue were detected using Western blotting,while their mRNA expression levels were detected using reverse transcription-polymerase chain reaction.Finally,the levels of IL-1β,IL-2,IL-6,IL-17A,and TNF-α in rat serum were detected using enzyme-linked immunosorbent assay.Results:Compared to the normal group,the model group exhibited notable pathological synovial tissue damage,along with significantly higher IL-1β,IL-6,and TNF-α levels(P<0.01)and a slightly higher IL-17 content(P>0.05).Furthermore,the Myd88,TLR4,and TRPV1 protein and mRNA expression levels and serum IL-1β,IL-2,IL-6,IL-17A,and TNF-α levels were all significantly higher in the model group than in the normal group(P<0.01).Compared to the model group,the moxibustion group exhibited a lower degree of synovial tissue pathological damage,along with significantly lower IL-1β,IL-6,and TNF-α levels(P<0.05 or P<0.01)and a lower IL-17 content without statistical significance(P>0.05).Moreover,the Myd88,TLR4,and TRPV1 protein and mRNA expression levels,and serum IL-1β,IL-2,IL-6,IL-17A,and TNF-α levels were all significantly lower in the moxibustion group than in the model group(P<0.01 or P<0.05).Conclusion:Mild moxibustion at Shenshu(BL23)and Zusanli(ST36)can effectively inhibit TLR4-MyD88 signaling pathway-mediated inflammatory factor expression in the synovial tissue of ankle joints of RA rats.Furthermore,the effect of moxibustion on synovial tissue inflammation in RA rats may be attributed to TRPV1 channel activation.

OBJECTIVE To explore the differences in the clinical laboratory test indexes between the patients with two different TCM syndrome types of eczema(dampness-heat infiltration type and non-dampness-heat infiltration type)and observe the distribution and drug resistance rate of pathogens isolated from the skin lesions so as to pro-vide bases for syndrome differentiation and reasonable use of antibiotics.METHODS A total of 180 patients with eczema who were positive for bacterial culture of skin secretions and were treated in Beijing Hospital of Traditional Chinese Medicine from Jan.2021 to Dec.2023 were enrolled in the study and were divided into the dampness-heat infiltration group with 134 cases and the non-dampness-heat infiltration group with 46 cases.The data of clini-cal laboratory test indexes were collected from the two groups of patients,the secretion specimens were sampled from the skin lesion sites,the isolated pathogens were identified by VITEK 2 Compact automatic microorganism analysis system,and the drug susceptibility testing was performed.RESULTS The direct bilirubin level of the dampness-heat infiltration group was(3.99±1.62)umol/L,higher than(3.46±1.12)umol/L of the non-damp-ness-heat infiltration group(P＜0.05),but both were in the normal range;there were no significant differences in other test indexes between the two groups.Totally 180 strains of pathogens were isolated from the 180 patients with eczema,156(86.67％)of which were gram-positive bacteria;Staphylococcus aureus(98 strains),Staphy-lococcus epidermidis(29 strains)and Staphylococcus haemolyticus(15 strains)were the predominant species of the gram-positive bacteria.The gram-negative bacteria accounted for 12.22％(22 strains).The drug resistance rate of the S.aureus strains to penicillin was up to 82.65％,and the isolation rate of methicillin-resistant Staphy-lococcus aureus(MRSA)was 12.24％(12/98);the drug resistance rates of the S.epidermidis strains to penicil-lin and erythromycin were 75.86％,and the drug resistance rate of the S.haemolyticus strains to erythromycin was 100.00％.CONCLUSIONS The gram-positive bacteria(dominated by the S.aureus)are dominant among the pathogens isolated from the skin lesion specimens of the eczema patients and are highly resistant to penicillin and erythromycin.The isolation rate of MRSA is relatuvely low.There is limited clinical significant difference in the direct bilirubin between the two groups.It is necessary to further explore more reliable indexes for syndrome dif-ferentiation.

Objective To explore the potential categories of exercise perception in elderly hip arthroplasty(HA)patients,analyze the prediction factors of different categories,and provide references for clinical nursing.Methods A convenience sampling method was used to select elderly HA patients treated in 6 orthopedic wards of 2 tertiary A hospitals in Guilin from October 2024 to February 2025.The general data questionnaire,Exercise Benefits and Barriers Perception Scale for Hip/Knee Throplasty Patients,Tampa Scale of Kinesiophobia,the 5-Factor Modified Frailty Index,and Self-Efficacy for Rehabilitation Outcome Scale were used for investigation.Latent profile analysis was used to identify the potential categories of exercise perception of elderly HA patients,and decision tree model was used to explore the core predictive factors of different profile.Results 222 valid questionnaires were collected,with an effective response rate of 96.52％.A total of 222 elderly HA patients were divided into 3 profiles:high benefit-low barrier group(19.82％),low benefit-high barrier group(22.07％),and mild barrier group(58.11％).Frailty,kinesophobia,rehabilitation self-efficacy,residence,educational level and daily exercise were significant predictors of latent profiles(P＜0.05),and the frailty was located in the root node of the decision tree model.Conclusion The level of exercise perception in elderly HA patients needs to be improved,and shows population heterogeneity.Medical staff should prioritize interventions for low benefit-high barrier and mild-barrier groups,implementing targeted strategies based on profile characteristics and predictive factors to improve their exercise perception.

Objective To develop a risk management system for complications associated with peripheral venous indwelling needles and to evaluate its application effect in order to reduce the risk of related complications.Methods We designed a comprehensive risk management system for peripheral intravenous indwelling needle complications,integrating specialized evidence-based guidelines with clinical practice insights,including 5 modules:intelligent assessment and decision support,intelligent inspection reminders,educational modules,collaborative case management procedures,and a knowledge base.Patients admitted to the neurology and internal classification metabolism departments of a tertiary hospital in Jilin Province were conveniently selected as the research subjects.Patients were assigned to a control group(from May to July 2022,before the implementation of the system)and an experimental group(from September to December 2022,after the implementation of the system).The incidence of complications,duration of indwelling needle,compliance rate of core indicators for nursing quality and number of nursing consultations were compared between the groups.Additionally,a self-administered questionnaire was used to assess clinical nurses'evaluations of the system.Results A total of 189 patients were included in the experimental group and 177 patients in the control group.The incidence of complications associated with peripheral intravenous indwelling needles was lower than that in the control group.The duration of indwelling peripheral intravenous needles was longer than that in the control group.The quality compliance rate of peripheral venous indwelling needle care in the experimental group was higher than that in the control group,and the number of consultation cases in the experimental group was higher than that in the control group.Comparisons between the 2 groups showed statistically significant differences for all indicators(P＜0.05).The nurses'recognition rates for the system's user-friendliness,professional guidance,and patient benefit were 77.78％,81.74％,and 82.13％,respectively.Conclusion The application of a peripheral vein indwelling needle complication risk management system can reduce the incidence of complications,prolong the duration of indwelling,and improve nursing quality.Nurses have a high recognition of this system.

Objective:To explore differences in the efficacy and safety of ruxolitinib in patients with myelofibrosis by age and to identify prognostic factors by analyzing clinical features and characteristics of chromosomes and gene mutations.Methods:This study retrospectively analyzed 188 patients with myelofibrosis who received ruxolitinib in the Department of Hematology, Qilu Hospital, Shandong University from January 1, 2017, to July 1, 2024. According to age at diagnosis, the patients were divided into the middle-aged group (≤55 years), young elderly group (56-65 years), and elderly group (>65 years). Clinical features, the characteristics of chromosomes and gene mutations, and the efficacy and safety of ruxolitinib treatment were compared across the three age groups. Independent factors influencing overall survival were identified through Cox proportional risk regression analysis.Results:Before treatment, the elderly group had more underlying comorbidities, a heavier symptom burden, higher leukocyte count, higher proportion and frequency of JAK2 mutations, and lower proportion of CALR mutations. The incidence of nondriver gene mutations was significantly higher in the young elderly group. After ruxolitinib treatment, the degree of reduction in spleen size did not differ significantly among the three groups. The length of the palpable spleen below the left costal margin reduced by more than 50% from baseline in 50.9% (27/53) of the patients in the middle-aged group, 43.5% (27/62) in the young elderly group, and 45.5% (20/44) in the elderly group ( P=0.720). No significant difference was observed among the three groups in the degree of reduction in Myeloproliferative Neoplasm Symptom Assessment Form (10-item version) score ( P=0.153), with a reduction in total symptom score by more than 50% achieved by 54.0% (27/50), 60.3% (41/68), and 66.7% (34/51) of the patients from the three groups, respectively ( P=0.429). The most common hematological adverse events were anemia and thrombocytopenia, while the most common nonhematological adverse events were electrolyte disturbance, elevated transaminase activity, and pulmonary infection. Multivariate analysis indicated that in ruxolitinib-treated patients with myelofibrosis, poor overall survival was independently predicted by increased age, reduced hemoglobin, percentage of bone marrow blasts ≥ 1%, absence of JAK2 mutations, chromosomal abnormalities, ≥2 high-molecular-risk mutations, and TP53 mutations. Conclusions:Patients with myelofibrosis stratified by age exhibited heterogeneous clinical features and gene mutation profiles but similar efficacy of ruxolitinib treatment and occurrence of adverse events.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

Carbapenem-resistant Enterobacteriaceae(CRE), one of the most urgent pathogens threatening human health worldwide, has posed a great challenge to clinical treatment. However, the imbalance between the lag in antibiotic research and development and the increase of CRE resistance has led to a "death threat" for patients infected with CRE, and it is urgent to explore new mechanisms of CRE resistance, which is closely related to the role of resistance genes, carbapenemases and efflux pumps. In addition, penicillin-binding protein, biofilms and iron carriers are expected to provide new research ideas to understand the drug resistance mechanism. The aim of this review is to summarize the mechanisms of CRE resistance and to provide new ideas for its treatment.

Objective:To analyze the relationship between clinicopathological features and germline mismatch repair (MMR) gene variants in endometrial cancer patients and to evaluate the clinical utility of germline multi-gene panel testing.Methods:This single-center, retrospective case series study included 100 endometrial cancer patients treated in Zhongshan Hospital, Fudan University between July 2022 and February 2024. We collected clinicopathological data and tumor molecular testing results. 61 cancer susceptibility genes were tested using next-generation sequencing, and the associations between the detection rate of germline variants and the clinicopathological characteristics in endometrial cancer patients were explored.Results:Among 100 patients, 28% (28/100) were found to have pathogenic variants in cancer susceptibility genes, of which 20 patients carried germline MMR gene variants and the remaining 8 patients carried variants in other cancer susceptibility genes. Of the 20 patients diagnosed with Lynch syndrome, only 40% (8/20) met the Chinese family history criteria for Lynch syndrome. Among 53 patients with intact MMR protein expression, 1 patient was identified with a germline MMR gene variant. In the 14 Lynch syndrome patients with confirmed microsatellite status, 5/14 of those showed low microsatellite instability or microsatellite stability. Germline multi-gene panel testing in all endometrial cancer patients additionally identified 1 Lynch syndrome patient and 8 patients with non-Lynch hereditary cancers.Conclusion:Current clinical screening criteria may miss some endometrial cancer patients with Lynch syndrome. Compared with traditional screening pattern, germline multi-gene panel testing not only improves the detection rate of Lynch syndrome in endometrial cancer patients but also identifies other hereditary cancer predispositions.