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.Epigenetic mechanism of Diwu Yanggan Capsule in improving liver regeneration microenvironment in a rat model of liver cancer
Minggang WANG ; Jiamei DONG ; Zhihua YE ; Xiang GAO ; Qi CHEN ; Xiaoqiao YU ; Hanmin LI
Journal of Clinical Hepatology 2026;42(2):362-371
ObjectiveTo investigate the epigenetic mechanism of Diwu Yanggan Capsule in improving liver regeneration microenvironment in a rat model of liver cancer by regulating DNA methylation, and to provide a basis for scientific clinical medication. MethodsA total of 48 specific pathogen-free Sprague-Dawley rats were divided into normal group, model group, and Diwu Yanggan Capsule group using a random number table, with 16 rats in each group. The Solt-Farber two-step method was used to establish a rat model of liver cancer. The rats in the Diwu Yanggan Capsule group were given Diwu Yanggan Capsule at a dose of 750 mg/kg/d by gavage, and those in the normal group and the model group were given an equal volume of normal saline by gavage. Liver tissue samples were collected from each group of rats after 16 weeks of continuous intervention; DNA methylation chips were used to analyze the change in DNA methylation in liver tissue, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for data analysis. In addition, the MeDIP-PCR technique was used to detect the changes in candidate differentially methylated genes such as YWHAB, ADCK2, ERLIN2, SEMA3B, and TPH2 in the liver tissue of rats, and Western blot and RT-qPCR were used to verify the expression of key methylated genes. The independent-samples t test was used for comparison of continuous data between two groups, and a one-way analysis of variance was used for comparison between multiple groups, while the least significant difference t-test was used for further comparison between two groups. ResultsThe DNA methylation chip analysis showed that compared with the normal group, the model group had significant methylation changes in the promoter region of 2 422 genes in liver tissue of rats. The GO functional enrichment analysis and the KEGG pathway enrichment analysis showed that these differentially methylated genes were significantly enriched in metabolic pathways such as steroid hormone biosynthesis and drug metabolism-cytochrome P450. Compared with the model group, the Diwu Yanggan Capsule group had significant reversal of promoter methylation in 1 650 genes, and the KEGG enrichment analysis showed that these genes were mainly involved in the pathways closely associated with cell proliferation, apoptosis, and microenvironment regulation, such as the calcium ion signaling pathway, the cAMP signaling pathway, and the extracellular factor signaling pathway. Compared with the model group, the Diwu Yanggan Capsule group had a significant increase in the promoter methylation level of the ADCK2 gene (P<0.05) and significant reductions in the promoter methylation levels of the ERLIN2 and TPH2 genes (all P<0.05). Compared with the model group, the Diwu Yanggan Capsule group had significant reductions in the mRNA expression levels and the protein expression levels of the ADCK2 (all P<0.05). ConclusionAbnormal DNA methylation in liver tissue participates in the development and progression of liver cancer. The effect of Diwu Yanggan Capsule on DNA methylation level is an important epigenetic mechanism for its effect in the prevention and treatment of liver cancer.
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 of traditional Chinese medicine–Western medicine integration in the diagnosis and treatment of moyamoya vasculopathy
Zhi LI ; Yang GAO ; Yijin XIANG ; Zhang SHI ; Zhigang YANG
Chinese Journal of Clinical Medicine 2026;33(4):703-711
Moyamoya vasculopathy (MMV) refers to a chronic cerebrovascular disease characterized by progressive stenosis or occlusion of the arteries around the circle of Willis, accompanied by the formation of collateral vessels. In traditional Chinese medicine (TCM), MMV falls into the categories of “stroke”, “vertigo”, and “headache”, among others. Its core etiology is related to congenital insufficiency and acquired malnourishment, with wind, fire, phlegm, deficiency, and stasis as the key pathogenic factors. Current Western medical diagnosis and treatment of MMV remain suboptimal, and TCM pattern differentiation has yet to be standardized. The most common clinical patterns are liver yang hyperactivity (associated with hemorrhagic symptoms) and qi deficiency with blood stasis (associated with ischemic symptoms). Treatment modalities include acupuncture, Chinese herbal formulas, and TCM–Western medicine integrated therapy. Clinical trial results have confirmed that integrated therapy offers certain benefits for MMV; however, there is a lack of relevant diagnostic and treatment guidelines as well as in-depth mechanistic studies. This article reviews the progress in TCM and Western medicine for the diagnosis and treatment of MMV and proposes a trinity diagnostic and therapeutic approach integrating “disease differentiation–pattern differentiation–staging”, which provides a reference for TCM–Western medicine integration management.
5.Evaluation of the scientific validity and applicability of the Dietary Guidelines for Americans, 2025‒2030 and its implications for China
Yuxian CHEN ; Yaqi LI ; Xiang GAO
Shanghai Journal of Preventive Medicine 2026;38(7):493-499
Dietary guidelines are nutritional policy tools formulated according to the global consensus on nutrition science and national conditions. Based on five core consensuses, namely dietary patterns, food group recommendations, full life cycle coverage, policy attributes, and sustainable diets, this paper reviews the scientific validity and applicability of the Dietary Guidelines for Americans, 2025-2030. With “Eat Real Food” as its core concept, this guideline has adjusted its food recommendations, population-specific guidance, and policy implementation pathways. However, some of its scientific evidence such as protein and fat recommendations is controversial, and the feasibility of its implementation is fraught with challenges. Rationally reflecting on the practical experience from the U.S., we suggest the revision of the Dietary Guidelines for Chinese Residents should optimize the dietary guidance system based on national conditions, and promote the policy transformation and practical application.
6.Anti-frostbite effect of miglitol on cold-exposed mice through UCP1-mediated thermogenic activation
Xiang LI ; Hongyuan LU ; Mingyu ZHANG ; Huan GAO ; Dong YAO ; Zihua XU
Journal of Pharmaceutical Practice and Service 2025;43(1):1-5
Objective To investigate the effect and mechanism of miglitol on regulating the energy metabolism of brown adipocytes by activating UCP1 and preventing cold injury in mice after cold exposure. Methods Primary brown adipocytes were induced into mature adipocytes, the effect of miglitol on the viability of brown adipocytes was investigated by MTT method, the lipid droplet consumption level of cells after drug administration was investigated by Oil Red O staining technology, and the level of UCP1, a key protein of thermogenesis in brown adipocytes, was detected by Western blotting. The activity of anti-frostbite was investigated in cold exposure at 4 ℃ and −20 ℃. KM mice, which were randomly divided into control group, cold exposure group, miglitol group and all-trans retinoic acid group, and after 7 days of repeated administration, the body surface temperature of mice was detected by infrared thermal imaging system, the anal temperature change was detected by anal thermometer, and the expression levels of UCP1 and PGC1-α in adipose tissue were detected by immunoblotting. Results Compared with the control group, the lipid droplet consumption and UCP1 expression levels in brown adipocytes in the miglitol group were significantly increased. The levels of body surface temperature and rectal temperature increased significantly after cold exposure, and the levels of UCP1 and PGC1α in the brown adipose tissue of mice increased significantly, which indicated that the miglitol could activate the critical proteins UCP1 and PGC1α of the thermogenesis pathway, increase the thermogenesis of mice after cold exposure, and thus improve the effect of cold injury for toe swelling. Conclusion Miglitol could play a role in improving cold injury and body temperature in mice by increasing the level of UCP1 and PGC1α, which are key targets of the thermogenesis pathway to promote the thermogenesis of brown fat.
7.The Ferroptosis-inducing Compounds in Triple Negative Breast Cancer
Xin-Die WANG ; Da-Li FENG ; Xiang CUI ; Su ZHOU ; Peng-Fei ZHANG ; Zhi-Qiang GAO ; Li-Li ZOU ; Jun WANG
Progress in Biochemistry and Biophysics 2025;52(4):804-819
Ferroptosis, a programmed cell death modality discovered and defined in the last decade, is primarily induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System Xc--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.
8.Investigation and analysis of iodine level in drinking water and iodine nutrition status of key populations in Guizhou Province in 2023
Demei ZHOU ; Hongbing YE ; Yang LI ; Hong XIANG ; Xuan LI ; Li YANG ; Jing GAO ; Chaozhong LEI
Chinese Journal of Endemiology 2025;44(9):719-725
Objective:To investigate the distribution of iodine in drinking water in external environment and the iodine nutrition status of key population in Guizhou Province, and to provide a basis for further precise implementation of prevention and control strategy of "adapting to local conditions, providing classified guidance, and scientifically supplementing iodine".Methods:From April to September 2023, a survey on the iodine level of residents' drinking water was conducted in administrative villages (neighborhood committees, hereafter referred to as administrative village) in 88 counties (districts) of 9 cities (prefectures) in Guizhou Province. At the same time, one township (town) was selected from each of the five districts of east, west, south, north and center of each county (district). From each township (town), 40 non-boarding students aged 8 - 10 years old from one primary school and 20 pregnant women were selected. Household edible salt sample and once random urine sample were collected for detection of salt iodine and urinary iodine levels.Results:The survey covered 16 492 administrative villages in 1 481 townships (towns), 88 counties (districts), 9 cities (prefectures) throughout the province. A total of 51 531 samples of residents' drinking water were collected, with a median water iodine level of 1.50 μg/L and a range of 0.01 - 98.70 μg/L. Among them, there were 16 284, 208, and 0 administrative villages with median water iodine levels < 10, 10 - < 40, and 40 - 100 μg/L, respectively, accounting for 98.74%, 1.26%, and 0, respectively. A total of 26 491 samples of household edible salt were collected from children and pregnant women, with a median salt iodine levels of 27.6 mg/kg. The coverage rate of iodized salt was 99.6% (26 395/26 491), and the qualified iodized salt consumption rate was 97.0% (25 708/26 491). And 17 657 urine samples from children and 8 834 urine samples from pregnant women were collected, with median urinary iodine levels of 222.1 and 164.4 μg/L, respectively. There were statistically significant differences in urinary iodine levels among children of different genders and ages ( Z = - 6.08, H = 19.17, P < 0.001). The results of correlation analysis showed that there was no correlation between urinary iodine of children and pregnant women and water iodine ( r = 0.01 0.02, P > 0.05), while urinary iodine of pregnant women was positively correlated with salt iodine ( r = 0.02, P = 0.041). Conclusions:The external environment of Guizhou Province is generally deficient in iodine. Under the universal salt iodization policy, children have sufficient iodine nutrition, and pregnant women have an appropriate level of iodine nutrition. Comprehensive prevention and control measures, mainly based on universal salt iodization, should be continuously carried out to eliminate the harm of iodine deficiency.
9.Electroacupuncture Modulates Alveolar Macrophage Polarization via the Vagus Nerve to Alleviate Pulmonary Inflammation in a Mouse Model of Chronic Obstructive Pulmonary Disease
Na LIU ; Linfeng WANG ; Yifan LI ; Shuwen XU ; Xinfang ZHANG ; Shuiying XIANG ; Heren GAO ; Zibing LIU
Journal of Nanjing University of Traditional Chinese Medicine 2025;41(10):1356-1364
OBJECTIVE To investigate the anti-inflammatory effect of electroacupuncture in mice with chronic obstructive pul-monary disease(COPD)and its underlying mechanisms.METHODS Forty C57BL/6 mice were randomly divided into normal group,model group,electroacupuncture(EA)group,vagotomy group,and vagotomy+EA group,with 8 mice in each group.Except for the normal group,all groups were exposed to cigarette smoke for 12 weeks to establish a COPD model.After model establishment,the vagotomy group and the vagotomy+EA group underwent left cervical vagotomy before EA.EA treatment was performed at the Feishu(BL13)and Zusanli(ST36)acupoints once daily for 20 minutes for a total of 14 days.After EA,the pulmonary ventilation function of the mice was detected by a pulmonary function analysis system;lung tissue pathology was observed by HE staining;the levels of inter-leukin(IL)-6,tumor necrosis factor-α(TNF-α),IL-10,and transforming growth factor-β(TGF-β)in lung tissue were detected by ELISA;the expression of CD86 and CD206 proteins in lung tissue was detected by Western blot;the distribution of F4/80+CD86+(M1 type)and F4/80+CD206+(M2 type)cells in lung tissue was determined by flow cytometry;the expression of CD86 and CD206 in lung tissue was observed by immunofluorescence.RESULTS Compared with the normal group,the model group showed significantly decreased lung function(P<0.01),obvious lung pathological damage,increased M1 proportion,IL-6,TNF-α,CD86 content and expression(P<0.05,P<0.01),and decreased M2 proportion,IL-10,TGF-β,CD206 content and expression(P<0.01).Compared with the model group,the EA group showed varying degrees of improvement in lung function and pathology;the M1 proportion,IL-6,TNF-α,and CD86 were reduced(P<0.05,P<0.01),while the M2 proportion,IL-10,TGF-β,and CD206 were increased(P<0.05,P<0.01).The vagotomy group showed worsened lung function and pathology,increased IL-6,TNF-α,and CD86 content and expression(P<0.05,P<0.01),and decreased IL-10,TGF-β,and CD206 content and expression(P<0.05,P<0.01).Compared with the EA group,the vagotomy+EA group showed increased M1 proportion,IL-6,TNF-α,and CD86 content and expression(P<0.01),and decreased M2 proportion,IL-10,TGF-β,and CD206 content and expression(P<0.05,P<0.01).CONCLUSION EA at Feishu(BL13)and Zusanli(ST36)acupoints can improve lung function and pulmonary inflammation in COPD mice,promoting the polarization of alveolar macrophages from M1 to M2,which is mediated by the vagus nerve.
10.Application and discussion of a typical teaching case library based on CBL in teaching of thyroid diseases
Zhuyao LI ; Rui YU ; Wansheng GAO ; Xiang LI
Modern Hospital 2025;25(4):630-633
Objective The purpose of this study is to explore the application effect of the typical teaching case library in thyroid disease teaching based on the case teaching method(CBL).Methods The standardized training students of resident physicians who rotated in our department from January 2022 to December 2024 were randomly divided into an experimental group and a control group.The experimental group students were taught using a typical teaching case library based on the CBL course,while the control group students were taught using traditional teaching methods.A total of 102 people were included in this study.We conduct a comprehensive assessment of teaching effectiveness through three methods:theoretical exams,practical skills as-sessments,and questionnaire surveys.Results The results indicate that the experimental group students were significantly higher than the control group in terms of theoretical exams,practical skills,and teaching satisfaction(P<0.05).Conclusion The typi-cal teaching case library based on CBL has a good application effect in thyroid disease teaching,which can improve students'learn-ing interest,clinical thinking ability,and practical operation level.It is worth promoting and applying in medical education.

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