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.

AIM: To explore the factors affecting the whole-eye astigmatism after pterygium excision combined with autologous limbal stem cell transplantation.METHODS: A retrospective analysis was conducted on the medical records of 42 patients(42 eyes)with primary pterygium admitted in the ophthalmology department of Xijing Hospital from January 2023 to October 2023. They underwent pterygium excision combined with autologous limbal stem cell transplantation. The maximum invasion depth of pterygium into the cornea was measured with anterior segment optical coherence tomography(AS-OCT)before operation, the length of the pterygium invading cornea, the width of the limbus and the area of the invading cornea were measured during the operation, and three-dimensional values of corneal astigmatism of anterior segment, index of surface variance(ISV), index of vertical asymmetry(IVA), best corrected visual acuity(BCVA)and whole-eye astigmatism were collected before and at 1 mo after surgery. Patients with astigmatism ≤0.50 D or >0.50 D of the whole eye at 1 mo after surgery were assigned to group A and B, respectively. The differences of clinical data before and at 1 mo after surgery between the two groups, and the correlation between pre-operative clinical indicators and whole-eye astigmatism were analyzed. The decision tree algorithm was performed to explore the influencing factors of whole-eye astigmatism at 1 mo postoperatively.RESULTS: The maximum invasion depth of pterygium in the group A was significantly less than that in the group B [80.00(40.00, 180.00)μm vs 175.00(123.00, 190.00)μm, P=0.002]. Preoperative BCVA(LogMAR), whole-eye astigmatism, cornea astigmatism, ISV, IVA and maximum invasion depth of pterygium were positively correlated with whole-eye astigmatism at 1 mo after surgery(rs=0.317, P=0.041; rs=0.545, P<0.001; rs=0.448, P=0.003; rs=0.389, P=0.011; rs=0.382, P=0.013; rs=0.391, P=0.010). The decision tree algorithm screened out two influential factors: the maximum invasion depth of pterygium into the cornea and preoperative whole-eye astigmatism. The risk of whole-eye astigmatism >0.50 D at 1 mo after operation was higher with maximum invasion depth of pterygium into the cornea >95 μm than that with ≤95 μm. Among the patients with whole-eye astigmatism >2.63 D before operation, the probability of residual whole-eye astigmatism >0.50 D was 88.9%, and the predictive model AUC was 0.804.CONCLUSION: The whole-eye astigmatism after pterygium resection is mainly affected by the maximum invasion depth of pterygium into the cornea and preoperative whole-eye astigmatism. When the maximum invasion depth of pterygium into the corneal is >95 μm and the whole-eye stigmatism is >2.63 D before surgery, the patient should receive surgical treatment as soon as possible in order to obtain good clinical benefits.

Purpose To investigate the feasibility of multi-sequence MRI-based radiomics for predicting epidermal growth factor receptor(EGFR)mutation status in brain metastases from non-small cell lung cancer(NSCLC).Materials and Methods This retrospective study included 237 patients with NSCLC brain metastases from the Second Xiangya Hospital of Central South University(January 1,2017 to December 31,2023)who underwent EGFR genetic testing.All patients underwent pretreatment brain MRI including contrast-enhanced T1-weighted,T2-weighted FLAIR,and T2-weighted sequences,along with chest CT for primary lung lesions.EGFR mutations were identified in 120 patients.Using December 31,2021 as the cutoff date,patients were divided into training(n=146)and validation(n=91)cohorts.Senior radiologists delineated brain metastases on multi-sequence MRI and primary lesions on CT.A total of 851 radiomic features were extracted using PyRadiomics.Following feature selection,machine learning models were constructed using support vector machine algorithm and compared with least absolute shrinkage and selection operator-derived radiomic signatures.Five models were developed:three single-sequence MRI models,a multi-sequence MRI fusion model,and a CT model,with diagnostic performance evaluated by area under the receiver operating characteristic curve.Results The multi-sequence MRI fusion model demonstrated superior performance across all imaging types.The least absolute shrinkage and selection operator and support vector machine models achieved training set area under the curve of 0.854(95%CI 0.748-0.960)and 0.948(95%CI 0.923-0.973),respectively,and validation set area under the curve of 0.810(95%CI 0.751-0.869)and 0.951(95%CI 0.917-0.985),respectively.The optimal prediction model utilized support vector machine algorithm with multi-sequence MRI features.Conclusion Pretreatment multi-sequence MRI radiomics combined with machine learning accurately predicts EGFR mutation status in NSCLC patients with brain metastases.

Objective To observe the effect of pirfenidone on myocardial fibrosis in rats and inves-tigate its underlying mechanism.Methods Twenty-four SD rats were randomly divided into sham-operation group,model group,low-and high-dose pirfenidone groups,with 6 rats in each group.Rat model of myocardial fibrosis was established by injecting isoprenaline into the tail vein,while normal saline was given to the sham operation group.Pirfenidone of 150 and 300 mg/(kg·d)were infused gastrically to the rats of low-and high-dose pirfenidone groups after modeling.Mas-son staining was used to observe the severity of myocardial fibrosis,immunohistochemical assay was employed to detect the expression of Collagen-1,NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome,cysteinyl aspartate-specific protease-1(Caspase-1),and Western blotting was performed to detect the protein levels of Collogen-1 and atrial desmo-plakin D(gasdermin D,GSDMD).Results The model group showed obvious myocardial fibrosis,and elevated expression of Collogen-1,NLRP3,Caspase-1 and GSDMD when compared with the sham operation group(P＜0.05).Low-and high-dose pirfenidone treatment resulted in signifi-cantly reduced myocardial fibrosis and reduced expression of Collogen-1,NLRP3,Caspase-1 and GSDMD[(8.14±1.40)％,(6.56±0.75)％vs(22.15±2.57)％,P＜0.05;0.14±0.03 vs 0.33±0.05,0.42±0.13,P＜0.05;(10.34±1.40)％,(10.33±3.40)％vs(23.22±1.99)％,P＜0.05;(15.67±0.56)％,(17.33±0.78)％vs(22.87±1.92)％,P＜0.05;0.43±0.06,0.46±0.11 vs 0.65±0.03,P＜0.05].Conclusion Pirfenidone inhibits cardiomyocyte pyroptosis and attenuates myocar-dial fibrosis through the NLRP3/Caspase-1/GSDMD signaling axis.

Purpose To investigate the feasibility of multi-sequence MRI-based radiomics for predicting epidermal growth factor receptor(EGFR)mutation status in brain metastases from non-small cell lung cancer(NSCLC).Materials and Methods This retrospective study included 237 patients with NSCLC brain metastases from the Second Xiangya Hospital of Central South University(January 1,2017 to December 31,2023)who underwent EGFR genetic testing.All patients underwent pretreatment brain MRI including contrast-enhanced T1-weighted,T2-weighted FLAIR,and T2-weighted sequences,along with chest CT for primary lung lesions.EGFR mutations were identified in 120 patients.Using December 31,2021 as the cutoff date,patients were divided into training(n=146)and validation(n=91)cohorts.Senior radiologists delineated brain metastases on multi-sequence MRI and primary lesions on CT.A total of 851 radiomic features were extracted using PyRadiomics.Following feature selection,machine learning models were constructed using support vector machine algorithm and compared with least absolute shrinkage and selection operator-derived radiomic signatures.Five models were developed:three single-sequence MRI models,a multi-sequence MRI fusion model,and a CT model,with diagnostic performance evaluated by area under the receiver operating characteristic curve.Results The multi-sequence MRI fusion model demonstrated superior performance across all imaging types.The least absolute shrinkage and selection operator and support vector machine models achieved training set area under the curve of 0.854(95%CI 0.748-0.960)and 0.948(95%CI 0.923-0.973),respectively,and validation set area under the curve of 0.810(95%CI 0.751-0.869)and 0.951(95%CI 0.917-0.985),respectively.The optimal prediction model utilized support vector machine algorithm with multi-sequence MRI features.Conclusion Pretreatment multi-sequence MRI radiomics combined with machine learning accurately predicts EGFR mutation status in NSCLC patients with brain metastases.

Objective To observe the effect of pirfenidone on myocardial fibrosis in rats and inves-tigate its underlying mechanism.Methods Twenty-four SD rats were randomly divided into sham-operation group,model group,low-and high-dose pirfenidone groups,with 6 rats in each group.Rat model of myocardial fibrosis was established by injecting isoprenaline into the tail vein,while normal saline was given to the sham operation group.Pirfenidone of 150 and 300 mg/(kg·d)were infused gastrically to the rats of low-and high-dose pirfenidone groups after modeling.Mas-son staining was used to observe the severity of myocardial fibrosis,immunohistochemical assay was employed to detect the expression of Collagen-1,NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome,cysteinyl aspartate-specific protease-1(Caspase-1),and Western blotting was performed to detect the protein levels of Collogen-1 and atrial desmo-plakin D(gasdermin D,GSDMD).Results The model group showed obvious myocardial fibrosis,and elevated expression of Collogen-1,NLRP3,Caspase-1 and GSDMD when compared with the sham operation group(P＜0.05).Low-and high-dose pirfenidone treatment resulted in signifi-cantly reduced myocardial fibrosis and reduced expression of Collogen-1,NLRP3,Caspase-1 and GSDMD[(8.14±1.40)％,(6.56±0.75)％vs(22.15±2.57)％,P＜0.05;0.14±0.03 vs 0.33±0.05,0.42±0.13,P＜0.05;(10.34±1.40)％,(10.33±3.40)％vs(23.22±1.99)％,P＜0.05;(15.67±0.56)％,(17.33±0.78)％vs(22.87±1.92)％,P＜0.05;0.43±0.06,0.46±0.11 vs 0.65±0.03,P＜0.05].Conclusion Pirfenidone inhibits cardiomyocyte pyroptosis and attenuates myocar-dial fibrosis through the NLRP3/Caspase-1/GSDMD signaling axis.

Objective To study the role of microRNA(miR)-483-3p in reducing myocardial fibrosis in rats,and explore the relationship between its mechanism and autophagy.Methods A total of 24 male SD rats were randomly divided into sham operation group,model group,blank transfec-tion group and high expression group,with 6 rats in each group.The blank transfection group and the high-expression group were pretreated with a single injection of adeno-associated virus(AAV)-blank transfection and AAV-miR-483-3p(5×1011 vg)in the tail vein,respectively.In 14 d later,the sham group was injected with 2.5 ml/(kg·d)normal saline for 14 d,and rat model of myocardial fibrosis was established by 2 mg/ml isoproterenol[2.5 ml/(kg·d)]injection through tail vein for 14 consecutive days.Myocardial pathological damage,severity of myocardial fibrosis,and expression levels of collagen-Ⅰ,microtubule-associated protein light chain 3(LC3),autoph-agy-related protein 5(Atg5)and autophagy degradation substrate(P62)in cardiomyocytes were evaluated and measured.Results Compared with the sham operation group,the model group had obviously larger myocardial fibrosis area,higher positive expression of Collagen-Ⅰ,and increased protein levels of Atg5 and LC3-Ⅱ/LC3-Ⅰ,and decreased expression level of P62 protein(P＜0.05).The myocardial fibrosis area,positive expression of Collagen-Ⅰ,the expression levels of Atg5 and LC3-Ⅱ/LC3-Ⅰ protein[(13.64±1.51)％vs(27.47±1.55)％,(13.48±3.07)％vs(30.91±2.45)％,0.98±0.17 vs 1.24±0.28,0.66±0.05 vs 1.26±0.09,P＜0.05]were significant-ly decreased,and the expression level of P62 was notably increased(0.91±0.11 vs 0.74±0.06,P＜0.05)in the high expression group than the model group.Conclusion MiR-483-3p attenuates myocardial fibrosis in rats,and the mechanism may be related to the inhibition of cardiomyocyte autophagy.

AIM:To investigate the differences in clinical features and therapeutic effects of the tea tree oil wipes combined with deep massages of the meibomian glands for different age groups of patients with demodex blepharitis.METHODS:The clinical data of 146 patients(292 eyes)diagnosed with demodex blepharitis, hospitalized in Department of Ophthalmology, Xijing Hospital from January 2023 to October 2023, was collected in this retrospective study, and the patients were divided into group A(64 cases with 128 eyes)aged ≤45 years old and group B(82 cases with 164 eyes)aged >45 years old according to different ages. The differences in total numbers of binocular mites, Schirmer I tests, symptom and sign scores before, and at 1 and 3 mo after the treatment of the tea tree oil wipes combined with deep massages of the meibomian glands were analyzed between the two groups.RESULTS: Before the treatments, the total number of the mites in the group A [7(6, 8)] was lower than that in the group B [8(7, 9.25); P<0.05]. The dry eye score in the group A [6(6, 7)] was lower than that in the group B [11(10, 12); P<0.001], and the ocular surface irritation symptom score in the group A [10(9, 11)] was higher than that in the group B [6(6, 7); P<0.001]. Both groups experienced a decrease in mite counts and improvement in symptoms and signs scores at 1 mo after treatment, and there was still a degree of improvement in all clinical indicators, with patients in the group B showing a further reduction in mite counts [-1(-3, 0)] even after the treatment was continued for 3 mo.CONCLUSION:The total numbers of mites in patients of older than 45 years old were higher than those in patients of ages younger than 45, and older patients have more serious dry eyes, with less serious symptoms of ocular surface irritation. The treatment can effectively reduce the number of mites in patients of different ages with demodex blepharitis, but the outcomes of Schirmer I tests do not change after the treatment. Longer treatment duration provide sustained clinical benefits.

Guided by the principle of multimedia instruction, the author puts forward a new teaching mode, in which theoretical teaching and experimental teaching can be processed synchronously based on campus network, interactive teaching is dominative, students are the principal part, and integral optimization of theoretical teaching and experimental teaching can be realized.