1.Increased risk of osteoporotic pathological fractures associated with sterol esters:evidence from IEU-GWAS and FinnGen databases
Zengjie GAO ; Xiang PU ; Lailai LI ; Yihui CHAI ; Hua HUANG ; Yu QIN
Chinese Journal of Tissue Engineering Research 2026;30(5):1302-1310
BACKGROUND:Although previous studies have reported associations between lipids and the risk of osteoporotic pathological fractures,the specific causal relationships between lipid level and osteoporotic pathological fractures remain unclear.OBJECTIVE:To elucidate the causal relationship between lipids and osteoporotic pathological fractures using a two-sample bidirectional Mendelian randomization analysis.METHODS:The data for 178 lipid metabolites were obtained from the IEU-GWAS database(developed by the MRC Integrative Epidemiology Unit at the University of Bristol,UK,which provides extensive summary data from genome-wide association studies),while osteoporotic pathological fracture data(from 173 619 European participants)were acquired from the FinnGen database(constructed by the Finnish national gene research program,focusing on investigating relationships between genomics and health/disease in the Finnish population).Osteoporotic pathological fracture data were used as the outcome variable,with lipids serving as exposures,for the bidirectional Mendelian randomization study to evaluate the causal effects of different lipids on osteoporotic pathological fractures.The UK Biobank database was employed as a validation set by switching the outcome variable to verify the findings horizontally.RESULTS AND CONCLUSION:(1)The inverse variance weighted analysis indicated that each unit increase in sterol ester(27∶1/20∶2)levels was associated with a 25.55%increase in the risk of osteoporotic pathological fractures(odds ratio=1.256,95%confidence interval:1.001-1.575,P=0.049),suggesting a significant positive correlation between elevated sterol ester levels and increased fracture risk.Reverse Mendelian randomization analysis revealed a significant negative association between osteoporotic pathological fractures and three types of phosphatidylcholine.Horizontal validation yielded consistent results,confirming sterol ester as a risk factor for osteoporotic pathological fractures.(2)The results indicate that sterol ester is a risk factor for osteoporotic pathological fractures,while phosphatidylcholine serves as a protective factor.These findings strengthen the evidence supporting the effect of lipids on the risk of osteoporotic pathological fractures.Although the GWAS data used in this study were derived from European populations,given the broad commonality of human genetics,the results provide valuable reference significance for improving osteoporosis in Chinese populations through lipid regulation.
2.Influencing factors of significant corneal astigmatism in pterygium patients during the perioperative period
Shiru CHAI ; Xiaofen ZHENG ; Hua YU ; Zhen LI ; Yuguo KANG
International Eye Science 2026;26(4):683-686
AIM: To explore the factors associated with significant corneal astigmatism during the perioperative period in patients with pterygium. METHODS: Patients with primary pterygium presenting at Shanxi Eye Hospital between February and June 2025 were enrolled. All patients underwent medical history collection. Pre- and postoperative data were obtained using Pentacam, anterior segment photography, Image J software, and anterior segment optical coherence tomography(AS-OCT). All patients underwent pterygium excision combined with autologous bulbar conjunctival flap transplantation under local infiltration anesthesia. RESULTS: A total of 76 patients(76 eyes)with pterygium were finally enrolled(30 males, 46 females)with a mean age of 62.2±8.2 y. The mean length of corneal invasion by pterygium was 3.61±0.89 mm, the mean depth of invasion into the anterior corneal surface was 0.15±0.09 mm, and the median area of corneal invasion was 10.25(6.90, 18.75)mm2. The median preoperative corneal astigmatism was 1.50(0.70, 5.45)D. Median astigmatism was 0.8(0.40, 1.28)D at 2 wk postoperatively and 0.60(0.30, 1.15)D at 1 mo postoperatively. Patient age showed a positive correlation with preoperative astigmatism, and with residual astigmatism at 2 wk and 1 mo postoperatively(all P<0.05). The length of corneal invasion was positively correlated with preoperative astigmatism and residual astigmatism at both postoperative timepoints(P<0.01). The depth of invasion showed no significant linear correlation with astigmatism at any stage(P=0.250, 0.761, 0.686). The area of corneal invasion was positively correlated with astigmatism at all stages(P<0.01). Patients were grouped based on significant astigmatism(≥1.0 D)and non-significant astigmatism(<1.0 D), after adjusting for other variables, age(P=0.031)and the area of corneal invasion(P=0.004)were identified as risk factors for significant astigmatism. Pterygium invasion length was not significant factors(P>0.05). Receiver operating characteristic(ROC)analysis showed the highest area under the curve(AUC)for the invasion area(AUC=0.915). CONCLUSION: Significant preoperative corneal astigmatism in pterygium patients is correlated with patient age, the length of corneal invasion, and the area of invasion. The area of pterygium invasion into the cornea is the strongest predictor of significant preoperative corneal astigmatism.
3.Increased risk of osteoporotic pathological fractures associated with sterol esters:evidence from IEU-GWAS and FinnGen databases
Zengjie GAO ; Xiang PU ; Lailai LI ; Yihui CHAI ; Hua HUANG ; Yu QIN
Chinese Journal of Tissue Engineering Research 2026;30(5):1302-1310
BACKGROUND:Although previous studies have reported associations between lipids and the risk of osteoporotic pathological fractures,the specific causal relationships between lipid level and osteoporotic pathological fractures remain unclear.OBJECTIVE:To elucidate the causal relationship between lipids and osteoporotic pathological fractures using a two-sample bidirectional Mendelian randomization analysis.METHODS:The data for 178 lipid metabolites were obtained from the IEU-GWAS database(developed by the MRC Integrative Epidemiology Unit at the University of Bristol,UK,which provides extensive summary data from genome-wide association studies),while osteoporotic pathological fracture data(from 173 619 European participants)were acquired from the FinnGen database(constructed by the Finnish national gene research program,focusing on investigating relationships between genomics and health/disease in the Finnish population).Osteoporotic pathological fracture data were used as the outcome variable,with lipids serving as exposures,for the bidirectional Mendelian randomization study to evaluate the causal effects of different lipids on osteoporotic pathological fractures.The UK Biobank database was employed as a validation set by switching the outcome variable to verify the findings horizontally.RESULTS AND CONCLUSION:(1)The inverse variance weighted analysis indicated that each unit increase in sterol ester(27∶1/20∶2)levels was associated with a 25.55%increase in the risk of osteoporotic pathological fractures(odds ratio=1.256,95%confidence interval:1.001-1.575,P=0.049),suggesting a significant positive correlation between elevated sterol ester levels and increased fracture risk.Reverse Mendelian randomization analysis revealed a significant negative association between osteoporotic pathological fractures and three types of phosphatidylcholine.Horizontal validation yielded consistent results,confirming sterol ester as a risk factor for osteoporotic pathological fractures.(2)The results indicate that sterol ester is a risk factor for osteoporotic pathological fractures,while phosphatidylcholine serves as a protective factor.These findings strengthen the evidence supporting the effect of lipids on the risk of osteoporotic pathological fractures.Although the GWAS data used in this study were derived from European populations,given the broad commonality of human genetics,the results provide valuable reference significance for improving osteoporosis in Chinese populations through lipid regulation.
4.Research progress on changes in retinal and choroidal structure and blood flow density after SMILE and FS-LASIK surgery
International Eye Science 2026;26(7):1198-1202
Femtosecond laser small-incision lenticule extraction(SMILE)and femtosecond laser-assisted in situ keratomileusis(FS-LASIK)are the mainstream corneal refractive surgeries at present. With the emergence of optical coherence tomography angiography(OCTA), an automatic and precise analytical technique, it has been widely applied in the evaluation of retinal and choroidal diseases, and has emerged as a novel tool for exploring the impacts of corneal refractive surgery on posterior ocular segment microcirculation. This article systematically reviews the characteristics of fundus microcirculation changes after SMILE and FS-LASIK surgeries, compares the differences in microcirculatory alterations between the two procedures, analyzes the limitations of existing studies, and discusses future research directions. It provides a theoretical basis for evaluating the safety of refractive surgery and selecting individualized surgical approaches.
5.The role of bile acid dynamics in inflammatory bowel disease and metabolic dysfunction-associated steatotic liver disease
Si-Rui Yu ; Run Sun ; Mei-Ya Shi ; Mei Yang ; Kun Chen ; Qiong Pan ; Ling Zhao ; Ming-Yue Wu ; Jin Chai
Liver Research 2026;10(1):35-50
The prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is higher among individuals with inflammatory bowel disease (IBD) than in the general population. Emerging evidence indicates that the development of MASLD in patients with IBD may occur independently of traditional metabolic risk factors, suggesting a unique pathophysiological mechanism distinct from conventional MASLD pathways. Bile acids (BAs), which act as critical signaling molecules in enterohepatic circulation, play an essential role in maintaining gastrointestinal homeostasis through bidirectional gut–liver axis communication. These molecules are increasingly recognized as pivotal regulators in the progression of both MASLD and IBD. While previous studies have characterized the dynamics of BA in blood or fecal samples under both conditions, a comprehensive understanding of their metabolic profiles and the associated interactions within the gut–liver axis is still lacking. This review synthesizes current evidence from studies employing BA metabolomics to investigate IBD and MASLD. By focusing on BA signatures, we summarize conserved alterations between these two conditions and their potential mechanisms of disease progression. Our review advances understanding of BA-mediated pathways in IBD and MASLD, providing a foundation for assessing their roles in contributing to the pathogenesis of MASLD in patients with IBD.
6.Consistency analysis of macular microvascular parameters measured by three OCTA devices in patients with long-term hydroxychloroquine administration
Hong JIANG ; Xinyue YU ; Yajing HAO ; Lijing CHAI
International Eye Science 2026;26(9):1616-1622
AIM:To compare the consistency of macular microvascular parameters measured by three devices: frequency-domain optical coherence tomography angiography(FD-OCTA)with split-spectrum amplitude-decorrelation angiography(SSADA), FD-OCTA with optical microangiography(OMAG), and swept-source OCTA(SS-OCTA), in patients with long-term hydroxychloroquine(HCQ)administration for rheumatoid arthritis(RA).METHODS:This prospective study enrolled patients treated with HCQ for 5 y due to RA who visited the Department of Ophthalmology of the hospital from January 2022 to November 2025. All subjects underwent a 6 mm×6 mm macular scan with three OCTA devices in random order, with a 5-minute interval between examinations by different devices. Images of the superficial capillary plexus(SCP)and deep capillary plexus(DCP)were acquired. The following microvascular parameters were compared: foveal superficial capillary plexus vessel density(F-SCP VD), parafoveal superficial capillary plexus vessel density(PF-SCP VD), foveal deep capillary plexus vessel density(F-DCP VD), parafoveal deep capillary plexus vessel density(PF-DCP VD), and the area of the foveal avascular zone(FAZ).RESULTS:A total of 34 female patients(68 eyes)treated with HCQ for 5 y due to RA were enrolled in this study, aged 38-58 y with a mean age of 49.3±5.05 y. Statistically significant differences were found in F-SCP VD, PF-SCP VD, F-DCP VD, PF-DCP VD, and FAZ area among measurements obtained by SS-OCTA, SSADA-based FD-OCTA, and OMAG-based FD-OCTA(all P<0.05). No statistically significant differences in all above parameters were observed between SSADA-based FD-OCTA and OMAG-based FD-OCTA(all P>0.05). FAZ areas measured by the three devices were highly positively correlated(|r|≥0.8, P<0.01). The F-SCP VD, PF-SCP VD, F-DCP VD, and PF-DCP VD values obtained by SSADA-based FD-OCTA and OMAG-based FD-OCTA were all highly positively correlated(|r|≥0.8, P<0.01). The PF-SCP VD and PF-DCP VD values measured by SS-OCTA versus SSADA-based FD-OCTA and OMAG-based FD-OCTA showed moderate positive correlations(0.5≤|r|<0.8, P<0.01). The F-SCP VD and F-DCP VD values measured by SS-OCTA versus SSADA-based FD-OCTA and OMAG-based FD-OCTA exhibited low positive correlations(0.3≤|r|<0.5, P<0.05). Bland-Altman plots demonstrated good agreement between SSADA-based FD-OCTA and OMAG-based FD-OCTA for the measurements of F-SCP VD, PF-SCP VD, F-DCP VD and PF-DCP VD. By contrast, poor agreement was observed when comparing SS-OCTA with SSADA-based FD-OCTA or OMAG-based FD-OCTA for measurements of F-SCP VD, PF-SCP VD, F-DCP VD and PF-DCP VD.Satisfactory agreement was found among the three OCTA devices for FAZ area measurements.CONCLUSION:SSADA-based FD-OCTA and OMAG-based FD-OCTA show favorable correlation and agreement in measuring macular vessel density of patients receiving HCQ, which allows cautious interchangeable use during clinical follow-up. The vessel density parameters measured by SS-OCTA were markedly different from those obtained by SSADA-based FD-OCTA and OMAG-based FD-OCTA; therefore, these devices cannot be directly interchanged.FAZ area measurements exhibit favorable inter-device agreement among the three systems, and interchangeability should be considered in the context of clinical practice.
7.Study Protocol of Expanded Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro-EXP)
Jae Hoon MOON ; Eun Kyung LEE ; Wonjae CHA ; Young Jun CHAI ; Sun Wook CHO ; June Young CHOI ; Sung Yong CHOI ; A Jung CHU ; Eun-Jae CHUNG ; Yul HWANGBO ; Woo-Jin JEONG ; Yuh-Seog JUNG ; Kyungsik KIM ; Min Joo KIM ; Su-jin KIM ; Woochul KIM ; Yoo Hyung KIM ; Chang Yoon LEE ; Ji Ye LEE ; Kyu Eun LEE ; Young Ki LEE ; Hunjong LIM ; Do Joon PARK ; Sue K. PARK ; Chang Hwan RYU ; Junsun RYU ; Jungirl SEOK ; Young Shin SONG ; Ka Hee YI ; Hyeong Won YU ; Eleanor WHITE ; Katerina MASTROCOSTAS ; Roderick J. CLIFTON-BLIGH ; Anthony GLOVER ; Matti L. GILD ; Ji-hoon KIM ; Young Joo PARK
Endocrinology and Metabolism 2025;40(2):236-246
Background:
Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making.
Methods:
This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes.
Conclusion
This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.
8.Establishment and evaluation of an animal model of heart failure with preserved ejection fraction integrating disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis
Xiaoqi WEI ; Xinyi FAN ; Feng JIANG ; Wangjing CHAI ; Jinling XIAO ; Fanghe LI ; Kuo GAO ; Xue YU ; Wei WANG ; Shuzhen GUO
Journal of Beijing University of Traditional Chinese Medicine 2025;48(4):501-515
Objective:
This study aimed to construct an animal model of heart failure with preserved ejection fraction (HFpEF) that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis and to evaluate it comprehensively.
Methods:
The HFpEF mouse model was constructed using a combination of Nω-nitro-L-arginine methyl ester (L-NAME) and a high-fat diet. According to the random number table method, SPF-grade male C57BL/6J mice were randomly assigned to the control, L-NAME, high-fat diet, and model groups, 10 in each group. Comprehensive observations and data collection on macroscopic signs (e.g., fur condition, mental state, stool and urine, oral and nasal condition, paw and body condition, etc.) and cardiac function were performed after 10 and 16 weeks of model induction. Additionally, the syndrome evolution was elucidated based on diagnostic criteria for clinical syndromes of heart failure. Furthermore, pathological and molecular biological examinations of myocardial tissue were performed to assess the stability and reliability of the model.
Results:
Mice in the model group showed typical characteristics of syndrome of qi deficiency and blood stasis, as well as syndrome of internal heat accumulation, including lethargy, slow response, dull paw color and oral/nasal color, exercise intolerance, abnormal platelet activation, dry feces, and dark yellow urine. The time window for these syndromes was between 10 and 16 weeks post-modeling. Cardiac function assessments revealed severe diastolic dysfunction, concentric myocardial hypertrophy, and myocardial fibrosis in the model group. Pathological examinations showed a significantly increased collagen deposition in the myocardial interstitium, enlarged cross-sectional area of cardiomyocytes, and sparse coronary microvasculature in the model group. Molecular biological analyses indicated marked activation of the inducible nitric oxide synthase/nuclear factor kappa-light-chain-enhancer of activated B cells/NOD-like receptor family pyrin domain containing 3 inflammatory pathway and significantly elevated inflammation levels in the myocardial tissue of the model group. Although mice in the L-NAME and high-fat diet groups also showed certain manifestations of qi deficiency syndrome, the substantial cardiac damage was relatively limited compared to the control group.
Conclusion
This study has constructed an animal model of HFpEF that integrates disease and syndrome based on the "deficiency-blood stasis-toxin" pathogenesis. The macroscopic and microscopic characteristics of this model are consistent with the manifestations of syndrome of qi deficiency and blood stasis, toxin syndrome, and syndrome of internal heat accumulation. Moreover, it can stably simulate the HFpEF state and reflect phenotypic changes in human disease. This model provides a suitable experimental platform to explore the pathogenesis of HFpEF, evaluate the effectiveness of traditional Chinese medicine (TCM) treatment regimens, and promote in-depth research on TCM syndromes of heart failure.
9.The mechanism of Laggerae Herba in improving chronic heart failure by inhibiting ferroptosis through the Nrf2/SLC7A11/GPX4 signaling pathway
Jinling XIAO ; Kai HUANG ; Xiaoqi WEI ; Xinyi FAN ; Wangjing CHAI ; Jing HAN ; Kuo GAO ; Xue YU ; Fanghe LI ; Shuzhen GUO
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):343-353
Objective:
To investigate the role and mechanism of the heat-clearing and detoxifying drug Laggerae Herba in regulating the nuclear factor-erythroid 2-related factor-2(Nrf2)/solute carrier family 7 member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) signaling pathway to inhibit ferroptosis and improve chronic heart failure induced by transverse aortic arch constriction in mice.
Methods:
Twenty-four male ICR mice were divided into the sham (n=6) and transverse aortic arch constriction groups (n=18) according to the random number table method. The transverse aortic arch constriction group underwent transverse aortic constriction surgery to establish models. After modeling, the transverse aortic arch constriction group was further divided into the model, captopril, and Laggerae Herba groups according to the random number table method, with six mice per group. The captopril (15 mg/kg) and Laggerae Herba groups (1.95 g/kg) received the corresponding drugs by gavage, whereas the sham operation and model groups were administered the same volume of ultrapure water by gavage once a day for four consecutive weeks. After treatment, the cardiac function indexes of mice in each group were detected using ultrasound. The heart mass and tibia length were measured to calculate the ratio of heart weight to tibia length. Hematoxylin and eosin staining were used to observe the pathological changes in myocardial tissue. Masson staining was used to observe the degree of myocardial fibrosis. Wheat germ agglutinin staining was used to observe the degree of myocardial cell hypertrophy. Prussian blue staining was used to observe the iron deposition in myocardial tissue. An enzyme-linked immunosorbent assay was used to detect the amino-terminal pro-brain natriuretic peptide (NT-proBNP) and glutathione (GSH) contents in mice serum. Colorimetry was used to detect the malondialdehyde (MDA) content in mice serum. Western blotting was used to detect the Nrf2, GPX4, SLC7A11, and ferritin heavy chain 1 (FTH1) protein expressions in mice cardiac tissue.
Results:
Compared with the sham group, in the model group, the ejection fraction (EF) and fractional shortening (FS) of mice decreased, the left ventricular end-systolic volume (LVESV) and left ventricular end-systolic diameter (LVESD) increased, the left ventricular anterior wall end-systolic thickness (LVAWs) and left ventricular posterior wall end-systolic thickness (LVPWs) decreased, the ratio of heart weight to tibia length increased, the myocardial tissue morphology changed, myocardial fibrosis increased, the cross-sectional area of myocardial cells increased, iron deposition appeared in myocardial tissue, the serum NT-proBNP and MDA levels increased, the GSH level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue decreased (P<0.05). Compared with the model group, in the captopril and Laggerae Herba groups, the EF, FS, and LVAWs increased, the LVESV and LVESD decreased, the ratio of heart weight to tibia length decreased, the myocardial cells were arranged neatly, the degree of myocardial fibrosis decreased, the cross-sectional area of myocardial cells decreased, the serum NT-proBNP level decreased, and the GSH level increased. Compared with the model group, the LVPWs increased, the iron deposition in myocardial tissue decreased, the serum MDA level decreased, and Nrf2, GPX4, SLC7A11, and FTH1 protein expressions in cardiac tissue increased (P<0.05) in the Laggerae Herba group.
Conclusion
Laggerae Herba improves the cardiac function of mice with chronic heart failure caused by transverse aortic arch constriction, reduces the pathological remodeling of the heart, and reduces fibrosis. Its mechanism may be related to Nrf2/SLC7A11/GPX4 pathway-mediated ferroptosis.
10.Plasma and hepatic free fatty acid, tricarboxylic acid cycle, and ketone bodies metabolic profiles in progressive Gao-Binge model
Anqin LI ; Luxin PANG ; Yuanyuan CHAI ; Qinwei YU ; Zhenzhou JIANG ; Luyong WANG
Journal of China Pharmaceutical University 2025;56(2):196-206
To investigate the correlation between hepatic lipid accumulation and the metabolic profiles of free fatty acids(FFAs), tricarboxylic acid (TCA) cycle, and ketone body in alcoholic fatty liver disease (AFLD), a chronic plus acute alcohol feeding model (Gao-Binge model) was employed using C57BL/6N mice to simulate different stages of AFLD. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to measure the levels of FFAs, TCA cycle intermediates, and ketone bodies in mouse liver tissue and plasma, followed by Pearson correlation analysis. The study revealed that both acute and chronic models showed significant increases in total FFAs, saturated FFAs and short-chain FFAs, as well as β-hydroxybutyric acid(HDBT) in plasma and liver, indicating FFA metabolic profile disturbances in the Gao-Binge model. Moreover, in both models, acetic acid (AA), 2-Methylbutyric acid (2-meBA), and HDBT displayed strong positive correlations with hepatic injury markers in plasma and liver samples (for instance, in the acute model plasma data, r = 0.834, 0.699, 0.818, P<0.05), while pyruvic acid (PRA) showed a strong negative correlation (r = −0.66, P<0.05). These findings suggest that FFAs, TCA cycle, and ketone body metabolism are disrupted in the alcoholic liver disease in mice model, and metabolites such as AA, 2-meBA, HDBT and PRA may serve as potential biomarkers for AFLD, which would be helpful in the diagnosis and treatment of this disease.


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