1.Targeting ER lipid raft-associated 1 reveals a coordinated cholesterol-dependent vulnerability in hepatocellular carcinoma
Yiming ZHANG ; Yushan HOU ; Xinxin WANG ; Kaikun XU ; Pei JIANG ; Siqi WANG ; Huimin KANG ; Hu ZHANG ; Jingzhuo JIN ; Xiaofen HUANG ; Zifeng LIU ; Songpeng YANG ; Jiaqi LIU ; Lingqiang ZHANG ; Fuchu HE ; Chunyan TIAN ; Aihua SUN
Clinical and Molecular Hepatology 2026;32(2):866-883
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.
2.Influencing factors for whole-eye astigmatism after pterygium excision combined with autologous limbal stem cell transplantation
Yanru HE ; Wanyue LI ; Jia LIU ; Yingwei WANG ; Zifeng ZHANG
International Eye Science 2025;25(2):286-291
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.
3.NEFA induces HIF-2α expression in dairy cow primary hepatocytes
Zifeng YANG ; Fanrong KONG ; Yan SUN ; Menglin LIU ; Jinxia LI ; Chenchen ZHAO ; Lin LEI ; Xinwei LI
Chinese Journal of Veterinary Science 2025;45(4):745-751
Ketosis is an energy metabolism disorder occurring frequently in periparturient dairy cows,primarily attributed to elevated non-esterified fatty acid(NEFA)levels resulting from nega-tive energy balance(NEB).Excessive NEFA will be incompletely oxidated into large amounts of ketone bodies or be re-esterified and deposit in the liver as a consequence of hepatic limited oxida-tive capacity,ultimately leading to ketosis and fatty liver.Hypoxic microenvironments are com-monly found during the progression of various liver diseases.Hypoxia inducible factor-2 alpha(HIF-2 alpha)has been identified as a crucial regulator of lipid metabolism.However,it is still un-clear the association between HIF-2α and disrupted lipid metabolism in the livers of in ketotic cows.This study aims to investigate the effect of high concentrations of NEFA on HIF-2α expres-sion and cellular oxygen homeostasis through bovine liver tissue and primary hepatocytes.In vivo,hepatic triglyceride(TAG)content was assessed to determine the extent of hepatic lipid accumula-tion,and HIF-2α protein and mRNA levels were analyzed by immunohistochemistry staining,Western blot and qRT-PCR assay in liver tissue samples from dairy cows;in vitro,bovine primary hepatocytes were treated with different concentrations of NEFA.Oil Red O staining and TAG con-tent assay were performed to determine hepatocellular steatosis extent,and immunofluorescence staining.Western blot,and qRT-PCR were performed to analyze HIF-2α expression,in addition,lu-minescent oxygen sensor[Ru(dpp)3]Cl2 was added to indicate intracellular oxygen levels.These results showed a significant increase in TAG content and elevated HIF-2α expression in the liver tissue of ketotic cows,and high concentrations of NEFA induced lipid accumulation,upregulation of HIF-2α expression,and intracellular hypoxia in bovine primary hepatocytes.These findings sug-gested that HIF-2α was significantly"activated"in the liver of ketotic cows and high concentration of NEFA-induced bovine primary hepatocytes,and that high concentrations of NEFA induced in-tracellular hypoxia in vitro.This study provides a potential molecular target for further investiga-tion of the mechanism underlying hepatic lipid metabolism disorders in ketotic cows.
4.A survey and analysis of the current status of radiotherapy in Hebei Province in 2024
Chenyang WANG ; Xinyi LI ; Yajing WU ; Zhiguo ZHOU ; Ming LIU ; Zhongchao HUO ; Xiaozhen WANG ; Hongyun SHI ; Weidong LIU ; Ji SONG ; Zifeng CHI ; Lixin DONG ; Yunchuan SUN ; Zhilin ZHANG ; Jun WANG
Chinese Journal of Radiation Oncology 2025;34(5):415-421
Objective:To investigate and analyze basic status of radiotherapy units in Hebei Province in 2024.Methods:Led by the Fourth Hospital of Hebei Medical University, the Radiation Oncology Branch of the Hebei Medical Association, and the Radiation Oncology Expert Committee of the Hebei Society of Clinical Oncology, a province-wide survey was conducted using structured questionnaires. The survey covered key aspects such as basic information of radiotherapy institutions, personnel allocation, equipment configuration, and implementation of radiotherapy techniques. Collected data were summarized and descriptively analyzed comparing with a 2013 survey of radiotherapy in Hebei Province.Results:All 158 radiotherapy institutions across Hebei Province participated in the survey. A total of 2273 radiotherapy professionals were reported, including 1317 radiation oncologists (57.94%), 332 medical physicists (14.61%), 71 radiotherapy engineers (3.12%), and 553 radiotherapy technologists (24.33%). The number of radiotherapy devices significantly increased from 121 in 2013 to 237 in 2024, including 68 domestic radiotherapy equipment. The current inventory includes 195 medical linear accelerators (2.61 units per million population), 2 cobalt-60 units, 27 afterloading machines, 9 tomotherapy (TOMO) systems, 3 CyberKnife units, and 1 proton therapy system. Three-dimensional conformal radiotherapy and stati intensity-modulated radiotherapy have been widely adopted across the province, while advanced techniques such as volumetric-modulated arc therapy, stereotactic body radiotherapy, and respiration-gated technology, and respiratory gating are gradually being implemented.Conclusions:In recent years, the configuration of radiotherapy personnel in Hebei Province has become more balanced, and the availability of precision radiotherapy equipment has significantly improved. There is a growing trend in the adoption of domestically manufactured radiotherapy equipment, marking substantial progress in the development of radiation oncology services in the region.
5.A survey and analysis of the current status of radiotherapy in Hebei Province in 2024
Chenyang WANG ; Xinyi LI ; Yajing WU ; Zhiguo ZHOU ; Ming LIU ; Zhongchao HUO ; Xiaozhen WANG ; Hongyun SHI ; Weidong LIU ; Ji SONG ; Zifeng CHI ; Lixin DONG ; Yunchuan SUN ; Zhilin ZHANG ; Jun WANG
Chinese Journal of Radiation Oncology 2025;34(5):415-421
Objective:To investigate and analyze basic status of radiotherapy units in Hebei Province in 2024.Methods:Led by the Fourth Hospital of Hebei Medical University, the Radiation Oncology Branch of the Hebei Medical Association, and the Radiation Oncology Expert Committee of the Hebei Society of Clinical Oncology, a province-wide survey was conducted using structured questionnaires. The survey covered key aspects such as basic information of radiotherapy institutions, personnel allocation, equipment configuration, and implementation of radiotherapy techniques. Collected data were summarized and descriptively analyzed comparing with a 2013 survey of radiotherapy in Hebei Province.Results:All 158 radiotherapy institutions across Hebei Province participated in the survey. A total of 2273 radiotherapy professionals were reported, including 1317 radiation oncologists (57.94%), 332 medical physicists (14.61%), 71 radiotherapy engineers (3.12%), and 553 radiotherapy technologists (24.33%). The number of radiotherapy devices significantly increased from 121 in 2013 to 237 in 2024, including 68 domestic radiotherapy equipment. The current inventory includes 195 medical linear accelerators (2.61 units per million population), 2 cobalt-60 units, 27 afterloading machines, 9 tomotherapy (TOMO) systems, 3 CyberKnife units, and 1 proton therapy system. Three-dimensional conformal radiotherapy and stati intensity-modulated radiotherapy have been widely adopted across the province, while advanced techniques such as volumetric-modulated arc therapy, stereotactic body radiotherapy, and respiration-gated technology, and respiratory gating are gradually being implemented.Conclusions:In recent years, the configuration of radiotherapy personnel in Hebei Province has become more balanced, and the availability of precision radiotherapy equipment has significantly improved. There is a growing trend in the adoption of domestically manufactured radiotherapy equipment, marking substantial progress in the development of radiation oncology services in the region.
6.NEFA induces HIF-2α expression in dairy cow primary hepatocytes
Zifeng YANG ; Fanrong KONG ; Yan SUN ; Menglin LIU ; Jinxia LI ; Chenchen ZHAO ; Lin LEI ; Xinwei LI
Chinese Journal of Veterinary Science 2025;45(4):745-751
Ketosis is an energy metabolism disorder occurring frequently in periparturient dairy cows,primarily attributed to elevated non-esterified fatty acid(NEFA)levels resulting from nega-tive energy balance(NEB).Excessive NEFA will be incompletely oxidated into large amounts of ketone bodies or be re-esterified and deposit in the liver as a consequence of hepatic limited oxida-tive capacity,ultimately leading to ketosis and fatty liver.Hypoxic microenvironments are com-monly found during the progression of various liver diseases.Hypoxia inducible factor-2 alpha(HIF-2 alpha)has been identified as a crucial regulator of lipid metabolism.However,it is still un-clear the association between HIF-2α and disrupted lipid metabolism in the livers of in ketotic cows.This study aims to investigate the effect of high concentrations of NEFA on HIF-2α expres-sion and cellular oxygen homeostasis through bovine liver tissue and primary hepatocytes.In vivo,hepatic triglyceride(TAG)content was assessed to determine the extent of hepatic lipid accumula-tion,and HIF-2α protein and mRNA levels were analyzed by immunohistochemistry staining,Western blot and qRT-PCR assay in liver tissue samples from dairy cows;in vitro,bovine primary hepatocytes were treated with different concentrations of NEFA.Oil Red O staining and TAG con-tent assay were performed to determine hepatocellular steatosis extent,and immunofluorescence staining.Western blot,and qRT-PCR were performed to analyze HIF-2α expression,in addition,lu-minescent oxygen sensor[Ru(dpp)3]Cl2 was added to indicate intracellular oxygen levels.These results showed a significant increase in TAG content and elevated HIF-2α expression in the liver tissue of ketotic cows,and high concentrations of NEFA induced lipid accumulation,upregulation of HIF-2α expression,and intracellular hypoxia in bovine primary hepatocytes.These findings sug-gested that HIF-2α was significantly"activated"in the liver of ketotic cows and high concentration of NEFA-induced bovine primary hepatocytes,and that high concentrations of NEFA induced in-tracellular hypoxia in vitro.This study provides a potential molecular target for further investiga-tion of the mechanism underlying hepatic lipid metabolism disorders in ketotic cows.
7.Application of Near-Infrared Autofluorescence Imaging Technology in Assisting Adrenal Gland Localization During Adrenal Tumor Resection:A Case Report and Literature Review
Chang CAI ; Xiao XIAO ; DianXin ZHOU ; YiLing LI ; Xiezhao LI ; Zifeng LUO ; Yifan LIU ; Song WANG
Journal of Endocrine Surgery 2025;25(3):101-108
The adrenal gland is a crucial endocrine organ, and adrenal tumors, mostly benign, often require surgical treatment. However, intraoperative localization of the adrenal gland is challenging due to its anatomical features. Laparoscopic surgery is widely used, but current laparoscopes lack real - time adrenal navigation. Near-infrared autofluorescence imaging (NIRAF) is a non-invasive technology that shows potential in adrenal localization, with limited reports globally and none in China. A 37-year-old female with a left adrenal nodule underwent retroperitoneoscopic left adrenal tumor resection. NIRAF technology, combined with laparoscopy, was used. The equipment had white light and near-infrared light modes.In the near-infrared light mode, the adrenal gland's autofluorescence was detected for intraoperative identification. Intraoperative NIRAF laparoscopy showed high-intensity fluorescence of the left adrenal tissue, clearly differentiating it from surrounding tissues.The surgery was completed within one hour without damage to surrounding organs. Postoperative monitoring of indicators such as blood pressure, aldosterone, adrenocorticotropic hormone, and white blood cell count was carried out. NIRAF technology has advantages in adrenal tumor resection, like improving surgical efficiency, reducing tissue manipulation, and lowering bleeding and infection risks. However, it has limitations such as weak light penetration and limited research. Further studies are needed to clarify its autofluorescence mechanism and evaluate its long-term effects.
8.Optimization of multi-campus management in large public hospitals:a case study of 5G-empowered multi-campus homogenization at a public hospital
Xiaohui HUANG ; Sulin ZHAO ; Linli ZHOU ; Kaiqi HUANG ; Zifeng LIU ; Liang PENG
Modern Hospital 2024;24(5):711-714,718
In recent years,the"One Hospital with Multiple Campuses"model has emerged in major public hospitals across China,providing intrinsic impetus and vitality for the expansion and balanced distribution of high-quality medical re-sources.This paper analyzed the current situation and challenges of the multiple campuses development in public hospitals within China,adopting a problem-oriented approach to explore optimized path to a unified management system.The aim was to establish a collaborative management model across campuses based predicated on the homogenization of systems,management,supervi-sion,professionals,and performance.Taking the Third Affiliated Hospital of Sun Yat-sen University as a case in this study,the paper reviewed and summarized management strategies and practical experience from the aspects of management model,resource allocation,information-orientation,homogenized management,and cultural development.Additionally,the article suggested to u-tilize 5G technology to empower homogenization across campuses.In this way,the hospital's overall operational efficiency can be improved,optimize resource allocation optimized,homogenized medical services ensured,and core competitiveness enhanced.These efforts will provide a reference for the high-quality development of multi-campus public hospitals.
9.Educational attainment increases the risk of developing allergic rhinitis and (or) eczema: a Mendelian randomization study based on genome-wide association studies in European patients
Rui ZHENG ; Zifeng LIU ; Zhuanggui CHEN ; Xuekun HUANG ; Peiying FENG ; Huijun QIU ; Yaxin LU ; Jingjing CHEN ; Yana ZHANG ; Jianrong ZHANG ; Qintai YANG
Chinese Journal of Preventive Medicine 2024;58(6):791-798
Objective:To determine the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema using Mendelian randomization (MR) analyses.Methods:This study was a secondary data analysis based on the summary data of genome-wide association studies (GWAS), which involved 293 723 participants (educational attainment) from the Social Science Genetics Association Consortium and 462 013 participants [allergic rhinitis and (or) eczema] from the UK Biobank. Genetic variants that were closely related to educational attainment were identified as instrumental variables. Two-sample MR analyses, including inverse-variance weighted (IVW), MR-Egger regression, weighted median method and weighted model-based estimation, were performed to investigate the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, in which the odds ratio ( OR) values were used as indicators. Results:A total of 70 single-nucleotide polymorphisms (SNPs) were chosen as instrumental variables. The MR-Egger regression results suggested that the genetic pleiotropy was unlikely to bias our results ( P=0.107). In the univariable MR analyses, IVW regression showed that the risk of allergic rhinitis and (or) eczema was OR=1.044 (95% CI: 1.020-1.069, P<0.001) and OR=1.170 (95% CI: 1.074-1.256, P<0.001), respectively, for the increase in the duration of education by one year or one standard deviation ( SD) (3.71 years). In the reverse MR analysis, IVW regression showed little evidence that allergic rhinitis and (or) eczema affected educational attainment ( OR=1.020, 95% CI: 0.927-1.023, P=0.683). The results of the weighted median method and weighted mode-based estimation were consistent with the results of IVW. Conclusion:This study suggests that there is a positive causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, which means that educational attainment can increase the occurrence of allergic rhinitis and (or) eczema.
10.Clinical features and impact factors in patients with open ocular trauma
Xiaxia* YANG ; Chunxia* MA ; Pengfei LIU ; Chaowei TIAN ; Manhong LI ; Dan HU ; Yusheng WANG ; Zifeng ZHANG
International Eye Science 2024;24(11):1846-1850
AIM:To summarize the clinical features and prognostic factors of patients with open ocular trauma in northwest China, and to explore the application of ocular trauma score(OTS)in open ocular trauma.METHODS:The clinical data of 91 patients(91 eyes)with open ocular trauma admitted to Xijing Hospital from June 2021 to June 2023 were retrospectively analyzed. The correlation analysis of visual acuity prognosis was carried out by age, treatment time, initial visual acuity, trauma zone and other factors, and the relationship between different OTS and prognostic visual acuity was discussed.RESULTS:Univariate analysis showed that age(0-20 years), treatment time(<24 h), initial visual acuity, trauma zone, trauma type(penetrating injury), anterior chamber hematoma, vitreous hematoma were correlated with prognostic visual acuity(all P<0.1); multivariate Logistic regression analysis showed that initial visual acuity and treatment time(<24 h)were risk factors(both P<0.05). There was a significant correlation between different OTS and prognostic visual acuity(rs=0.639,P<0.001).CONCLUSION:Patients with open ocular trauma should be diagnosed and treated as early as possible. The main factors influencing the visual prognosis are age, treatment time, initial visual acuity, trauma zone, trauma type, anterior chamber hematoma and vitreous hematoma. OTS has good application value in visual acuity evaluation of open ocular trauma prognosis.

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