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.

Lung transplantation is a definitive treatment for end-stage lung disease and can significantly improve patient prognosis. However, postoperative complications such as infection, rejection, ischemia-reperfusion injury and chronic lung allograft dysfunction intertwine to form a complex pathological network, posing persistent challenges to long-term patient survival. In 2025, research teams worldwide have made systematic progress in the field of basic lung transplantation research. By integrating cutting-edge technologies including single-cell multi-omics, spatial transcriptomics and novel animal models, significant breakthroughs have been achieved in the evolutionary dynamics of drug-resistant infections, molecular mechanisms of immune regulation, programmed cell death, optimization of donor lung protection strategies and early warning of chronic lung allograft dysfunction. This article systematically reviews the representative advances in basic lung transplantation research worldwide in 2025, and deeply analyzes the implications of mechanistic breakthroughs for optimizing diagnosis and treatment strategies, aiming to anchor the direction for innovative breakthroughs and clinical translation in basic lung transplantation research.

ObjectiveTo explore the possible mechanisms of Wenyang Huazhuo Formula （温阳化浊方， WHF） in improving reproductive aging from the perspective of the ovarian mechanical microenvironment. MethodsThe experiment included five groups， 3-month group （20 female mice at 3 months of age）， 6-month group （20 female mice at 6 months of age）， 6-month + WHF group （20 female mice at 5 months of age treated with WHF）， 9-month group （20 female mice at 9 months of age）， and 9-month + WHF group （20 female mice at 8 months of age treated with WHF）. The 6-month + WHF group and 9-month + WHF group were orally administered WHF 41.2 g/（kg·d） once daily for 4 consecutive weeks. The other three groups received no intervention. Reproductive hormone levels were measured by ELISA. HE staining was used to count the numbers of various stages of follicles. Ovarian hyaluronic acid （HA） content and collagen fiber content were measured to evaluate the ovarian mechanical microenvironment. Superovulation was performed to observe the number of eggs obtained， as well as the number of offspring and birth weight to assess fertility. The in vitro fertilization and blastocyst culture of oocytes from female offspring in each group were observed to evaluate the effect of WHF on offspring reproductive potential. ResultsCompared with the 3-month group， the 6-month group and 9-month group showed significantly decreased serum levels of gonadotropin-releasing hormone （GnRH）， follicle-stimulating hormone （FSH）， and luteinizing hormone （LH）， decreased ovarian collagen content， and reduced numbers of primordial and secondary follicles. In contrast， the numbers of primary follicles， antral follicles， and atretic follicles increased. The levels of anti-Müllerian hormone （AMH）， ovarian HA content， and the fertilization rate， cleavage rate， and blastocyst formation rate of oocytes from offspring were significantly lower （P＜0.05）. Compared with the 6-month group， the 6-month + WHF group showed significantly reduced serum levels of GnRH， FSH， and LH， with a significant decrease in primary follicles， antral follicles， and atretic follicles as well as increase of AMH levels， ovarian HA content， number of primordial and secondary follicle， egg count， and offspring birth weight （P＜0.05）. Compared with the 9-month group， the 9-month + WHF group exhibited reduced GnRH， FSH， and collagen fiber content， as well as reduced number of primary follicles， antral follicles， and atretic follicles. However， AMH levels， ovarian HA content， number of primordial and secondary follicle， egg count， offspring numbers， birth weight， fertilization rate， cleavage rate， and blastocyst formation rate of oocytes from offspring all significantly increased （P＜0.05）. ConclusionWHF can significantly improve the ovarian reserve， fertility， and reproductive potential in offspring during reproductive mid-life and late-life stages. Its effect may be related to the remodeling of the mechanical microenvironment of aging ovaries. Moreover， the effect on the mechanical microenvironment remodeling of late-stage ovaries and the improvement of the offspring reproductive potential is more significant.

Objective To develop a Self-Report Scale of Symptoms for Post Intensive Care Syndrome-Family(PICS-F)and validate its reliability and validity,providing a scientific tool for healthcare professionals to comprehensively assess post intensive care syndrome-family.Methods Based on the symptom experience dimension of Symptom Management Theory,a preliminary version of the scale was developed through literature analysis,semi-structured interviews,expert consultations,and a pilot survey.A convenience sampling method was used to conduct the pre-trial version of the scale questionnaire survey on 442 family members of ICU patients at a tertiary A comprehensive hospital in Wuhan from June to September 2024.The test of the validity and reliability was conducted.Results The developed scale consists of 4 dimensions and 20 items.Exploratory factor analysis identified 4 factors,with a cumulative variance contribution rate of 70.921％.The content validity index at the scale level was 0.941,and the content validity indices for individual items ranged from 0.809 to 1.000.Confirmatory factor analysis indicated that the model fit indices were within acceptable ranges.The overall Cronbach's αcoefficient for the scale was 0.941,and the split-half reliability was 0.832.Conclusion The Self-Report Scale of Symptoms for PICS-F demonstrates good reliability and validity.It can comprehensively reflect the primary symptoms of PICS-F,and can serve as an effective measurement tool for clinicians to assess PICS-F in family members of ICU patients.

Decreased endometrial receptivity is a critical factor contributing to the decline in fertility among women of advanced age. With the increase of age, the endometrium exhibits diminished hormonal responsiveness, a phenomenon known as inflammaging, and an imbalance in immune cell populations. These changes impede the processes of endometrial epithelial-mesenchymal transition and decidualization, thereby negatively impacting embryo implantation and reducing overall fertility potential. Furthermore, adverse lifestyle choices, exposure to environmental factors, inflammatory conditions, and repeated interventions within the uterine cavity can result in pathological aging of the endometrium that does not align with its chronological age. This misalignment may be associated with the emergence of various reproductive disorders, even in younger women. This paper seeks to investigate the relationship between pathological aging of the endometrium and reproductive disorders, particularly in the context of embryo implantation, with the aim of providing new insights into the pathogenesis, clinical diagnosis, and treatment of reproductive disorders.

Mesenchymal stem cells (MSCs) are an effective therapeutic strategy to delay aging in dogs, they are prone to aging and have poor genetic stability when cultured for a long time in vitro. Therefore, it is of great significance to explore a method to improve the anti-aging ability of MSCs. Previous studies have shown that sirtuin 6 (SIRT6) plays an important role in anti-aging. This study constructed MSCs with overexpressed SIRT6 gene. Through Giemsa staining and senescence-associated β-galactosidase staining, it was found that SIRT6 significantly enhances the anti-aging capacity of MSCs. Transmission electron microscopy imaging and the detection of oxidative stress-related indicators revealed that SIRT6 improves the anti-aging capacity of MSCs by maintaining mitochondrial homeostasis and reducing oxidative stress levels. Transcriptome sequencing analysis revealed that SIRT6 mainly acted on phosphatidylinositol-3-kinase, mitogen-activated protein kinase and other aging and inflammation related pathways. In the establishment and verification of aging models in mice and dogs, it was found that the spatial memory ability of the model mice was significantly increased after intravenous transplantation of SIRT6 overexpression cells, the organ index was also significantly changed, and the anti-oxidative capacity of the dogs and mice blood was improved. The morphology of the spleens and livers in the SIRT6 overexpression cell treatment group could be effectively restored, and the expression levels of aging and inflammation-related proteins were significantly decreased. This study provides a new idea for the study of SIRT6-mediated anti-aging of MSCs.
Animals ; Dogs ; Mesenchymal Stem Cells/metabolism* ; Sirtuins/genetics* ; Aging/physiology* ; Mice ; Oxidative Stress ; Mesenchymal Stem Cell Transplantation

The amino acid sequences of the OmpA protein isolated from Escherichia coli QML2206-1(E.coli QML2206-1)in our laboratory were analyzed for homology with different strains of OmpA proteins using bioinformatics software,and the OmpA protein was analyzed for its physicochemical properties,transmembrane structure and signal peptide prediction,B-cell anti-genic epitope prediction,secondary and tertiary structure prediction.The OmpA gene fragment was ligated with pET-32a vector to construct a prokaryotic expression vector,which was purified by a nickel column affinity purification system after prokaryotic expression and optimization of ex-pression conditions in BL21(DE3).The purified recombinant protein was fully mixed with Freund's adjuvant to immunize mice,and the levels of mouse-specific IgG antibody and the expression levels of cytokines CD4,CD8 and IL-4 in mouse serum were detected by ELISA,and the immuno-protective effect was evaluated by mouse attack protection test.OmpA protein is a hydrophilic protein with no transmembrane structural domains and a secondary structure consisting mainly of irregular coils(47.98％)and α-helices(29.77％),with 12 antigenic epitopes that can bind to anti-bodies produced by B cells.The recombinant protein OmpA with a relative molecular mass of a-bout 55 kDa was successfully obtained by prokaryotic expression,and the highest expression was induced by IPTG concentration of 0.000 4 mmol/L for 6 h at 37 ℃.The serum-specific IgG anti-body potency of recombinant protein immunized mice was up to 1∶32 000;the expression levels of CD4,CD8 and IL-4 in the serum of immunized mice were elevated compared with those of the con-trol group.The survival rate of mice was 80％and 40％after attack with minimum lethal dose(MLD)and 2 times minimum lethal dose(2MLD),respectively.OmpA recombinant protein has good antigenicity and certain immunoprotective effects,and this study provides a technical basis for the next step in the development of a genetically engineered subunit vaccine against yak-appli-cable E.coli based on OmpA protein.

Objective:This study aims to investigate the differences in emotional status and cognitive function among patients with vestibular migraine (VM), Meniere′s disease (MD), and their comorbidity (VMMD), and to analyze key factors influencing cognitive function.Methods:This cross-sectional study included 96 outpatients (32 males, 64 females, aged 21-73 years) from the Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, between December 2022 and December 2023. The study population consisted of 31 VM patients (VM group), 36 MD patients (MD group), and 29 VMMD patients (VMMD group), along with 32 healthy controls (16 males, 16 females, aged 19-74 years). Cognitive function was assessed using the Montreal Cognitive Assessment (MoCA), while emotional status and somatization symptoms were evaluated through the Generalized Anxiety Disorder scale, Patient Health Questionnaire Depression scale, Symptom Checklist-90, and the Self-rating Somatization Symptom scale. Multiple linear regression analysis was conducted to explore the influence of different variables on cognitive function.Results:The total MoCA score in the VMMD group (26.0 [24.5, 28.0]) was significantly lower than that in the control group (28.0 [27.0, 29.0]) and the MD group (28.0 [26.0, 30.0]) ( P=0.006). VMMD patients exhibited significant impairments in specific cognitive domains, including visuospatial/executive function, delayed recall, and orientation ( P<0.05). Patients with VM, MD, and VMMD showed higher rates of anxiety, depression, and somatization symptoms compared to the control group ( P<0.05), with the VMMD group experiencing the most severe emotional distress. Multiple linear regression analysis identified education level and vestibular disease type as key factors affecting cognitive function, with a university-level education predicting higher MoCA scores ( P<0.001), while VMMD was associated with cognitive decline ( P<0.01). Conclusions:Patients with VM and MD, particularly those with comorbid VMMD, exhibit significant emotional distress. Cognitive impairments are present in VM and VMMD patients, affecting different cognitive domains. These factors should be comprehensively considered in clinical assessments to develop more effective treatment strategies.

Objective:To evaluate the sound localization ability of patients with different degrees of unilateral conductive hearing loss (UCHL) in quiet and noisy environments, and to explore the changes and characteristics of sound localization.Methods:This was a cross-sectional study. 41 patients with UCHL were hospitalized in Shandong Provincial ENT Hospital from January to April 2024, including 22 males and 19 females, aged 18-55 years old, with an average age of 36.9 years. According to the pure-tone average (PTA) of 500, 1000 and 2000 Hz in the suffered ear, subjects were divided into slight-mild UCHL group (20 numbers) and moderate-moderately severe UCHL group (21 numbers). 21 patients with normal hearing (NH) were enrolled as controls. All subjects were assessed through pure-tone audiometry, horizontal sound localization test (including azimuth identification test in quiet and noisy environments), Chinese edition short form of Spatial Hearing Questionnaire (C-SHQ12) and twelve-item version of Speech, Spatial, and Qualities of Hearing Scale (SSQ12). SPSS, version 26.0, was used for statistical analysis.Results:There were significant differences in the root-mean-square errors (RMSE) of the sound localization azimuth identification test in quiet and noisy environments among the NH group, slight-mild UCHL group, and moderate-moderately severe UCHL group (Quiet: F=29.109, P<0.001; Noisy: F=24.351, P<0.001). This presented statistically marked difference in the RMSEs between the two listening environments in the slight-mild UCHL group ( t=-4.911, P<0.001). There was a statistical difference in the RMSEs between the normal and affected sides of the subjects in the slight-mild UCHL group in the quiet environment ( t=-2.055, P<0.05), but not in the noisy environment. For moderate-moderately severe UCHL subjects, there were no differences in the RMSEs between the quiet and noisy environments ( P>0.05). What’s more，no significant differences were found between normal side and affected side in both environments ( P>0.05). The RMSEs of UCHL patients in quiet and noisy environments were positively correlated with PTA of air-conduction in the suffered ears (Quiet: r=0.681, P<0.001; Noisy: r=0.346, P<0.05). RMSEs in quiet and noisy environments were negatively correlated with the average localization scores in C-SHQ12 (Quiet: r=-0.576, P<0.001, Noisy: r=-0.613, P<0.001) and in SSQ12 (Quiet: r=-0.634, P<0.001, Noisy: r=-0.663, P<0.001). Conclusions:The sound localization ability of UCHL subjects decreased compared with those with normal hearing, and the RMSE gradually increased with the worse of air conduction hearing threshold. The localization ability of UCHL subjects was further reduced in the noisy environment compared with that in the quiet environment. The slight-mild UCHL subjects had better localization performance in the normal ears while worse in the suffered ears, however, when they were in noisy environment or their hearing loss deteriorated, the localization advantage of the normal ears was no longer obvious, and both sides of the subjects presented poor localization performance.

With the continuous advancement of modern medical technology,wearable patch ultrasound technology is emerging as a crucial tool for real-time and dynamic monitoring of visual information within the human body.This technology seamlessly integrates the precision of ultrasound with the convenience of wearable devices,enabling continuous and dynamic monitoring of internal physiological parameters,and providing a more accurate and efficient method for medical diagnosis and health monitoring.Wearable patch ultrasound can obtain the image information of human body in real time,including the structure and functional status of the heart,blood vessels,muscles,and bones,facilitating early disease detection and diagnosis.This review summarizes the major clinical application scenarios and frontier research advances of wearable patch ultrasound and discusses the opportunities and challenges in the future.