1.Three-dimensional Electrical Impedance Tomography for Monitoring Gastric Hemorrhage
Zi-Han ZHAO ; Bo SUN ; Jing-Shi HUANG ; Zhi-Wei LI ; Yang WU ; Nan LI ; Jia-Feng YAO ; Tong ZHAO
Progress in Biochemistry and Biophysics 2026;53(4):1062-1075
ObjectiveGastric hemorrhage is one of the most common and life-threatening emergencies of the upper digestive tract. Early identification and continuous monitoring are essential for reducing rebleeding rates and mortality, particularly within the critical early hours after onset. Although endoscopy and radiological imaging can accurately localize bleeding sites, these approaches are invasive, resource-intensive, and unsuitable for continuous bedside monitoring. Electrical impedance tomography (EIT), as a noninvasive and radiation-free functional imaging technique, offers real-time visualization of conductivity distribution and has the potential for detecting intragastric bleeding based on the electrical contrast between blood and surrounding gastric tissues. In this study, a three-dimensional gastric EIT (3D-gEIT) framework is proposed to achieve noninvasive, real-time, and dynamic monitoring of gastric hemorrhage, with emphasis on spatial localization and quantitative volume assessment. MethodsA three-dimensional upper-abdominal simulation model incorporating the stomach, gastric wall, gastric contents, and surrounding tissues was established. Three electrode configurations, namely the dual layer ring, the four layer staggered ring, and the opposed dual plane array, were designed and systematically compared to evaluate their influence on depth sensitivity and spatial resolution. Based on the Tikhonov-Noser hybrid regularization scheme, a region-clustering constraint was introduced to develop the TK-Noser-RCC algorithm. This approach aggregates spatially adjacent elements with similar conductivity variations, thereby enhancing structural continuity and suppressing isolated noise artifacts. To validate the proposed framework, an upper-abdominal physical phantom was constructed using agar to simulate background tissue conductivity. Hemispherical high-conductivity inclusions with volumes ranging from 10 ml to 50 ml were attached to the inner gastric wall to mimic localized bleeding under different gastric filling states. Boundary voltages were acquired under a 120 kHz excitation current and reconstructed using the TK-Noser-RCC algorithm. Furthermore, an in vivo animal experiment was performed using a porcine model with adult-scale abdominal dimensions. A total of 100 ml of autologous blood was injected incrementally into the stomach to simulate progressive gastric hemorrhage, and time-difference EIT reconstruction was conducted at each injection stage to assess the dynamic system response under physiological conditions. ResultsSimulation results demonstrated that the opposed dual-plane electrode array achieved superior depth sensitivity distribution and spatial resolution. For a 40 ml hemorrhage model, the average ICC and SSIM improved by 55.9% and 38.8% compared with the dual-layer ring configuration, and by 64.0% and 39.5% compared with the four-layer staggered configuration. The proposed region-clustering constraint significantly enhanced reconstruction stability. Under added Gaussian noise of 40 dB and 30 dB, ICC values remained approximately 0.85, indicating effective artifact suppression and preservation of boundary integrity. In physical phantom experiments, reconstructed hemorrhage volumes increased approximately linearly with the preset hemispherical volumes, and the reconstructed high-conductivity regions closely matched the actual bleeding locations. Both empty-stomach and full-stomach conditions were evaluated, demonstrating that the opposed dual-plane configuration maintained stable imaging performance across varying gastric contents. In the animal experiment, reconstructed low-impedance regions expanded progressively with increasing injected blood volume. The spatial localization of the hemorrhage remained stable throughout the procedure, and no significant artifacts were observed. Quantitative analysis showed that reconstructed volume and average conductivity variation exhibited an approximately linear growth trend with injected blood volume, confirming the sensitivity of the system to dynamic intragastric conductivity changes. ConclusionThe proposed 3D-gEIT framework enables quantitative reconstruction of gastric hemorrhage volume and spatial distribution with improved depth sensitivity, structural continuity, and noise robustness compared with conventional EIT approaches. By integrating optimized electrode configuration and a region-clustering-constrained reconstruction algorithm, the system provides stable dynamic monitoring under both controlled phantom conditions and in vivo physiological environments. This method offers a noninvasive, real-time, and low-cost imaging strategy for early diagnosis, postoperative monitoring, and bedside surveillance of gastric bleeding.
2.Olfactory Receptors Expressed in The Intestine and Their Functions
Pei-Wen YANG ; Meng-Meng YUAN ; Ying ZHOU ; Peng LI ; Gui-Hong QI ; Ying YANG ; Zhong-Yi MAO ; Meng-Sha ZHOU ; Xiao-Shuang MAO ; Jian-Ping XIE ; Yi-Nan YANG ; Shi-Hao SUN
Progress in Biochemistry and Biophysics 2026;53(3):534-549
Olfactory receptors (ORs) form the largest superfamily of G protein-coupled receptors (GPCRs). Traditionally recognized for their role in the nasal olfactory epithelium, where they mediate the sense of smell, accumulating evidence has firmly established their ectopic expression in non-olfactory tissues, including the intestine, lungs, and kidneys. The intestine, as the primary site for nutrient digestion and absorption, harbors a highly complex chemical environment. To adapt to this environment, the gut employs a sophisticated network of “chemosensors” to monitor luminal contents and maintain homeostasis. Among these sensors, intestinal ORs have emerged as crucial functional components, serving as a molecular bridge that connects environmental chemical signals—such as food-derived odorants—to specific physiological responses. This discovery has significantly deepened our understanding of how dietary flavors and compounds influence intestinal physiology at the molecular level. This review systematically summarizes the expression profiles, ligand classification, and biological functions of ORs within the gastrointestinal tract. Studies indicate that intestinal ORs exhibit distinct spatial distribution patterns across different gut segments and display cell-type specificity, particularly within enterocytes and enteroendocrine cells. These receptors function as versatile sensors capable of recognizing a wide variety of ligands, including exogenous dietary components, gut microbiota metabolites such as short-chain fatty acids, and endogenous small molecules like azelaic acid. Upon activation by specific ligands, intestinal ORs trigger intracellular signaling cascades, primarily involving the AC-cAMP-PKA pathway or calcium influx channels. A major focus of this review is to elucidate the molecular mechanisms by which these receptors regulate the secretion of gut hormones. Activation of specific ORs in enteroendocrine cells has been shown to stimulate the release of hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and serotonin (5-HT), thereby modulating systemic energy metabolism, glucose homeostasis, and gastrointestinal motility. Furthermore, the review addresses the critical roles of ORs in immune regulation and pathology. Evidence suggests that specific ORs contribute to the maintenance of intestinal immune homeostasis and may offer protection against inflammation. Beyond their involvement in inflammatory responses, ORs such as Olfr78 have been shown to regulate the differentiation and function of intestinal endocrine cells. Similarly, Olfr544 has been demonstrated to alleviate intestinal inflammation by remodeling the gut microbiome and metabolome. These findings collectively suggest that specific ORs hold promise as therapeutic targets for mitigating intestinal inflammation and maintaining gut homeostasis. Additionally, the review explores the emerging role of ORs in cancer. Although OR expression is often downregulated in tumor tissues compared to normal mucosa, activation of specific ORs by certain ligands can inhibit tumor cell proliferation and migration and induce apoptosis via pathways such as MEK/ERK and p38 MAPK. Conversely, other receptors, such as OR7C1, may serve as biomarkers for cancer-initiating cells. In conclusion, intestinal ORs represent a vital component of the gut’s sensory network. The review also discusses the translational potential of these findings. By elucidating the precise pairing relationships between dietary components and specific ORs, novel therapeutic strategies could be developed. Intestinal ORs may thus emerge as promising targets for nutritional and pharmacological interventions in metabolic diseases, inflammatory bowel diseases, and malignancies.
3.Phenotypic distribution and population genetic frequency analysis of ABO and Rh blood group antigens among voluntary blood donors in Yantai
Hewei SONG ; Xiaojun ZHANG ; Qun XU ; Xiangzhong LIU ; Nan GUO ; Di SUN
Chinese Journal of Blood Transfusion 2026;39(1):69-75
Objective: To investigate the distribution characteristics of ABO and Rh blood group antigen phenotypes among blood donors in the Yantai, Shandong. Methods: Blood samples from 310 180 voluntary blood donors in Yantai collected from January 2019 to December 2023 were tested for ABO and Rh blood group antigens using standard serological methods. RhD-negative samples were further typed for C, c, E, and e antigens. Population genetic analysis of blood groups was performed: allele frequencies were inferred from ABO phenotypes, and Rh allele/haplotype frequencies were estimated based on the proportion of RhD-negative donors and CcEe antigen typing, followed by Hardy-Weinberg equilibrium testing. Results: The phenotypic distribution frequency of ABO blood groups was B(32.72%)>O(28.93%)>A(27.65%)>AB(10.70%). The inferred allele frequencies were r(53.74%)>q(24.78%)>p(21.48%), consistent with Hardy-Weinberg equilibrium (P>0.05). A total of 1 872 Rh-negative donors (0.603%) were identified. The most common Rh phenotypes were ccdee (59.56%) and Ccdee (30.18%). The distribution of Rh antigen phenotypes deviated significantly from Hardy-Weinberg equilibrium (χ
=37.15, P<0.001), with the cde haplotype showing the highest frequency. There was no statistically significant difference in ABO blood group distribution between RhD-positive and RhD-negative donors (P>0.05). Conclusion: The ABO blood group distribution among voluntary blood donors in Yantai is generally stable and consistent with population genetic equilibrium, whereas the Rh antigen phenotype distribution deviates from equilibrium, indicating potential underlying genetic structural differences.
4.Modified Morrow procedure for the treatment of hypertrophic obstructive cardiomyopathy: A single-center retrospective study in 318 patients
Jie LI ; Fan WENG ; Nan CHEN ; Yongxin SUN ; Changfa GUO ; Chunsheng WANG ; Yi LIN ; Wenjun DING
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2026;33(03):431-437
Objective To summarize the clinical efficacy of modified Morrow surgery in the treatment of hypertrophic obstructive cardiomyopathy. Methods A retrospective analysis was conducted on the clinical data of patients with hypertrophic obstructive cardiomyopathy treated with modified Morrow surgery at Zhongshan Hospital Affiliated to Fudan University from 2020 to 2023. Results A total of 318 patients were enrolled, including 156 males and 162 females, with an average age of (55.6±13.1) years. Preoperative echocardiography showed a mean interventricular septal thickness of (18.1±3.8) mm, peak left ventricular outflow tract pressure difference of (86.4±24.9) mm Hg. The surgery time was (162.3±51.0) min, extracorporeal circulation time was (80.9±31.0) min, and aortic occlusion time was (44.8±20.8) min. After the surgery, transesophageal echocardiography showed that the interventricular septal thickness was (11.0±1.8) mm and left ventricular outflow tract peak pressure difference was (9.4±5.1) mm Hg. The incidence rate of postoperative complete left bundle branch block was 45.3%, Ⅲ° atrioventricular block was 3.8%, and postoperative newly developed atrial fibrillation was 3.1%. The postoperative hospital stay was (6.6±4.9) days, and one perioperative death occurred, with a mortality rate of 0.3%. The follow-up time was (10.3±9.4) months, during which the transthoracic echocardiography revealed a ventricular septal thickness of (12.9±2.9) mm and a peak left ventricular outflow tract pressure difference of (13.9±10.0) mm Hg. Conclusion The modified Morrow procedure for the treatment of hypertrophic obstructive cardiomyopathy is safe and effective, with good results in the short and medium term.
5.Effect and Mechanism of Liangyi Paste on Hepatic Lipid Deposition in Naturally Aged Mice with High-fat Diet via Cuproptosis/Oxidative Stress Pathway
Meiling ZHANG ; Yuanguang DONG ; Xiaofei SUN ; Jiaxin WANG ; Yu LIU ; Jingxuan ZHU ; Qun WANG ; Nan SONG ; Guoyuan SUI ; Lianqun JIA
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):91-99
ObjectiveTaking the cuproptosis/oxidative stress pathway as the entry point, this study investigated the effect and mechanism of Liangyi Paste on hepatic lipid deposition in naturally aged mice fed with a high-fat diet. MethodsAfter adaptive feeding, 80 ten-week-old male C57BL/6 mice were used. Thirty of them were randomly divided into three groups (10 mice per group): The 12-month-old control group (12MCON), the 15-month-old control group (15MCON), and the 15-month-old group with a high-fat diet (15MHFD). The 12MCON and 15MCON groups were continuously fed a standard diet, while the 15MHFD group started receiving a high-fat diet at 12 months of age. Tissue samples were collected at the corresponding time points for each group. The remaining 50 mice were randomly divided into five groups (10 mice per group): the 20-month-old control group (20MCON), the model group, and the low-, medium-, and high-dose Liangyi Paste groups (2.91 , 5.82 , 11.64 g·kg-1·d-1, respectively). The 20MCON group was continuously fed a standard diet, while the other groups started receiving a high-fat diet at 15 months of age. At 18 months of age, the Liangyi Paste groups were administered the corresponding doses of Liangyi Paste by gavage, while the 20MCON and model groups were given an equal volume of saline by gavage. After 8 weeks of continuous gavage (when the mice reached 20 months of age), tissue samples were collected. Hepatic TG levels were measured using assay kits; liver histology and lipid deposition were observed via hematoxylin-eosin (HE) and oil red O staining; reactive oxygen species (ROS) were detected by enzyme-linked immunosorbent assay (ELISA); Cu2+, superoxide dismutase (SOD), and malondialdehyde (MDA) levels were measured by colorimetry; mRNA and protein expression of genes related to cuproptosis and oxidative stress pathways were analyzed by Real-time polymerase chain reaction(Real-time PCR) and Wes automated protein expression system. ResultsCompared with 12MCON, the 15MCON group showed significantly increased hepatic TG, Cu2+, ROS, and MDA levels (P<0.01), decreased SOD (P<0.01), hepatocyte swelling, and disordered arrangement. The mRNA and protein levels of ferredoxin 1 (FDX1), dihydrolipoamide S-acetyltransferase (DLAT), heat shock protein 70 (HSP70), dihydrolipoamide dehydrogenase (DLD), pyruvate dehydrogenase E1 subunit-β (PDHB), nuclear factor erythroid 2-related factor 2 (Nrf2), and peroxisome proliferator-activated receptor γ (PPARγ) were significantly elevated (P<0.05, P<0.01). Compared with 15MCON group, the 15MHFD and 20MCON groups exhibited further increases in TG, Cu2+, ROS, and MDA (P<0.01), reduced SOD (P<0.01), and aggravated hepatocyte swelling and disorder. There were increased lipid droplets with mild vacuolization in the 15MHFD group, and no significant lipid deposition was observed in the 20MCON group. FDX1, DLAT, HSP70, DLD, PDHB, Nrf2, and PPARγ mRNA and protein levels were significantly increased (P<0.05, P<0.01). Compared with 20MCON group, the model group demonstrated markedly elevated TG, Cu2+, ROS, and MDA (P<0.01), reduced SOD (P<0.01), severe hepatic steatosis, and upregulated expression of FDX1, DLAT, HSP70, DLD, PDHB, Nrf2, and PPARγ mRNA and proteins (P<0.05, P<0.01). All abnormalities were significantly reversed after Liangyi Paste treatment. ConclusionLiangyi paste can ameliorate hepatic lipid deposition in naturally aged mice with a high-fat diet by modulating the cuproptosis/oxidative stress pathway.
6.Effects of Guilu Erxian Glue on gut microbiota in rats with knee osteoarthritis:machine learning and 16S rDNA analysis
Fucheng GU ; Meixin YANG ; Weixin WU ; Weijun CAI ; Yangyi QIN ; Mingyi SUN ; Jian SUN ; Qiudong GENG ; Nan LI
Chinese Journal of Tissue Engineering Research 2026;30(4):1058-1072
BACKGROUND:The Guilu Erxian Glue consists of Testudinis Plastrum,Cornu Cervi,Lycii Fructus,and Ginseng Radix.In earlier clinical observations,it is discovered that using Guilu Erxian Glue to treat patients with liver-kidney deficiency type knee osteoarthritis effectively alleviated knee pain,increased the range of motion,and improved walking ability.However,the exact mechanism by which oral administration of Guilu Erxian Glue can produce local therapeutic effects on the knee joint is still unclear.OBJECTIVE:To investigate the effects of Guilu Erxian Glue on gut microbiota in rats with knee osteoarthritis and to evaluate its mechanism using 16S rDNA sequencing and machine learning analysis.METHODS:Totally 18 female SD rats were randomly divided into three groups:blank group,model group,and Guilu Erxian Glue group,with 6 rats in each group.A knee osteoarthritis model was prepared using the destabilization of the medial meniscus surgical method.After successful modeling,the Guilu Erxian Glue group was given a decoction of Guilu Erxian Glue by gavage,while the blank and model groups were given an equal amount of distilled water.After 28 days of continuous intervention,high performance liquid chromatography was used to detect the active ingredients of Guilu Erxian Glue.MRI imaging was used to observe the condition of rat knee articular cartilage.Fecal samples were collected;DNA was extracted using a kit,amplified and purified by PCR,and an Illumina sequencing library was constructed.The Illumina MiSeq platform was used for high-throughput sequencing to generate raw sequence data.After obtaining the raw data,QIIME2 software was used to process the data.Linear Discriminant Analysis Effect Size analysis and random forest algorithm were used to screen for differential species in microbial data.KEGG and MetaCyc functional pathway analyses were used to explore the association between key microbial communities and experimental groups.Linear discriminant analysis effect values and random forest algorithm were used to screen for differential species.Association networks were used to analyze the interactions between microbial communities,and machine learning methods were used to analyze the composition and changes of gut microbiota.RESULTS AND CONCLUSION:(1)LC-MS component identification was conducted on the traditional Chinese medicine formula of Guilu Erxian Glue,and a total of 7 effective ingredients were identified.(2)MRI imaging showed that synovitis scope of high-density shadows in rats of the Guilu Erxian Glue group was reduced,and the degeneration of medial femoral condyle cartilage was less than that in the model group.(3)16S rDNA sequencing showed that the model group rats exhibited significant microbial imbalance,with a significant decrease in the abundance of Firmicutes and Bacteroidetes at the phylum level,while the proportion of Proteobacteria increased significantly(P<0.05).The gut microbiota structure of rats in the Guilu Erxian Glue group was significantly improved,and the proportion of Firmicutes and Bacteroidetes increased,restoring a more diverse microbiota composition,approaching that of the blank group(P<0.05).(4)KEGG and MetaCyc functional pathway analysis showed that the Guilu Erxian Glue group significantly activated multiple metabolic pathways,including amino acid metabolism,lipid metabolism,and biotin synthesis pathways(P<0.05).(5)The results indicate that Guilu Erxian Glue contains seven active ingredients,and the changes in gut microbiota of knee osteoarthritis rats were analyzed using 16S rDNA sequencing.Guilu Erxian Glue can significantly improve the imbalance of gut microbiota,restore the abundance of beneficial bacteria,and have a significant impact on the composition of gut microbiota,providing scientific basis for the efficacy and mechanism of Guilu Erxian Glue.
7.Effects of Guilu Erxian Glue on gut microbiota in rats with knee osteoarthritis:machine learning and 16S rDNA analysis
Fucheng GU ; Meixin YANG ; Weixin WU ; Weijun CAI ; Yangyi QIN ; Mingyi SUN ; Jian SUN ; Qiudong GENG ; Nan LI
Chinese Journal of Tissue Engineering Research 2026;30(4):1058-1072
BACKGROUND:The Guilu Erxian Glue consists of Testudinis Plastrum,Cornu Cervi,Lycii Fructus,and Ginseng Radix.In earlier clinical observations,it is discovered that using Guilu Erxian Glue to treat patients with liver-kidney deficiency type knee osteoarthritis effectively alleviated knee pain,increased the range of motion,and improved walking ability.However,the exact mechanism by which oral administration of Guilu Erxian Glue can produce local therapeutic effects on the knee joint is still unclear.OBJECTIVE:To investigate the effects of Guilu Erxian Glue on gut microbiota in rats with knee osteoarthritis and to evaluate its mechanism using 16S rDNA sequencing and machine learning analysis.METHODS:Totally 18 female SD rats were randomly divided into three groups:blank group,model group,and Guilu Erxian Glue group,with 6 rats in each group.A knee osteoarthritis model was prepared using the destabilization of the medial meniscus surgical method.After successful modeling,the Guilu Erxian Glue group was given a decoction of Guilu Erxian Glue by gavage,while the blank and model groups were given an equal amount of distilled water.After 28 days of continuous intervention,high performance liquid chromatography was used to detect the active ingredients of Guilu Erxian Glue.MRI imaging was used to observe the condition of rat knee articular cartilage.Fecal samples were collected;DNA was extracted using a kit,amplified and purified by PCR,and an Illumina sequencing library was constructed.The Illumina MiSeq platform was used for high-throughput sequencing to generate raw sequence data.After obtaining the raw data,QIIME2 software was used to process the data.Linear Discriminant Analysis Effect Size analysis and random forest algorithm were used to screen for differential species in microbial data.KEGG and MetaCyc functional pathway analyses were used to explore the association between key microbial communities and experimental groups.Linear discriminant analysis effect values and random forest algorithm were used to screen for differential species.Association networks were used to analyze the interactions between microbial communities,and machine learning methods were used to analyze the composition and changes of gut microbiota.RESULTS AND CONCLUSION:(1)LC-MS component identification was conducted on the traditional Chinese medicine formula of Guilu Erxian Glue,and a total of 7 effective ingredients were identified.(2)MRI imaging showed that synovitis scope of high-density shadows in rats of the Guilu Erxian Glue group was reduced,and the degeneration of medial femoral condyle cartilage was less than that in the model group.(3)16S rDNA sequencing showed that the model group rats exhibited significant microbial imbalance,with a significant decrease in the abundance of Firmicutes and Bacteroidetes at the phylum level,while the proportion of Proteobacteria increased significantly(P<0.05).The gut microbiota structure of rats in the Guilu Erxian Glue group was significantly improved,and the proportion of Firmicutes and Bacteroidetes increased,restoring a more diverse microbiota composition,approaching that of the blank group(P<0.05).(4)KEGG and MetaCyc functional pathway analysis showed that the Guilu Erxian Glue group significantly activated multiple metabolic pathways,including amino acid metabolism,lipid metabolism,and biotin synthesis pathways(P<0.05).(5)The results indicate that Guilu Erxian Glue contains seven active ingredients,and the changes in gut microbiota of knee osteoarthritis rats were analyzed using 16S rDNA sequencing.Guilu Erxian Glue can significantly improve the imbalance of gut microbiota,restore the abundance of beneficial bacteria,and have a significant impact on the composition of gut microbiota,providing scientific basis for the efficacy and mechanism of Guilu Erxian Glue.
8.Effect of Gypenosides on MAFLD Mice and Its Molecular Mechanism Based on Classical/Non-classical Ferroptosis Pathways
Yu LIU ; Yupeng PEI ; Jiaxin WANG ; Jingxuan ZHU ; Xiaofei SUN ; Qun WANG ; Peng CUI ; Nan SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):99-107
ObjectiveTo explore the effect of gypenosides (GPs) on liver lipid deposition in metabolism-associated fatty liver disease (MAFLD) mice and its mechanism based on classical/non-classical ferroptosis. MethodsEight male C57BL/6 mice in a blank group and 32 male apolipoprotein E gene knockout (ApoE-/-) mice were randomly divided into a model group, a low-dose GPs (GPs-L) group, a high-dose GPs (GPs-H) group, and a simvastatin (SV) group. Starting from the second week, mice in the blank group were given a maintenance diet, and the other four groups were fed a high-fat diet daily. After eight weeks of feeding, mice in the GPs-L and GPs-H groups were given GPs of 1.487 mg·kg-1·d-1 and 2.973 mg·kg-1·d-1, respectively, and mice in the SV group were given simvastatin of 2.275 mg·kg-1·d-1. Mice in the blank group and the model group were given saline of equal volume by gavage for four weeks. The content of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the serum of mice in each group was detected by an automatic biochemical analyzer. The level of non-esterified fatty acid (NEFA) and TG in the mouse liver was measured by the kit. The change in liver tissue structure and lipid deposition was observed by hematoxylin-eosin (HE) and oil red O staining. The levels of coenzyme Q10 (CoQ10), glutathione (GSH), malondialdehyde (MDA), and Fe2+ in serum, as well as nicotinamide adenine dinucleotide phosphate [NAD(P)H] in the liver were detected by enzyme-linked immunosorbent assay (ELISA). The expression of ferroptosis suppressor protein 1 (FSP1) in the liver of mice was observed by the immunohistochemical (IHC) method, and the expression of genes and proteins related to classical and non-classical ferroptosis pathways was analyzed by real-time polymerase chain reaction (Real-time PCR) and Wes automated protein expression analysis system. ResultsCompared with those in the blank group, the levels of TC, TG, LDL-C, ALT, and AST in serum and TG and NEFA in the liver in the model group were significantly increased, and the level of HDL-C in serum was significantly decreased (P<0.01). The liver tissue structure changed, and there were fat vacuoles of different sizes and a large number of red lipid droplets, with obvious lipid deposition. The level of CoQ10 and GSH in serum and NADH in the liver were significantly decreased, while the level of MDA and Fe2+ in serum was significantly increased (P<0.01). The mRNA and protein expressions of cystine/glutamate transporter (xCT/SLC7A11), glutathione peroxidase (GPX4), p62, nuclear factor E2-related factor 2 (Nrf2), and FSP1 were significantly decreased, and the mRNA and protein expressions of tumor antigen (p53), spermidine/spermine N1-acetyltransferase 1 (SAT1), arachidonate 15-lipoxygenase (ALOX15), and Kelch-like epichlorohydrin-associated protein-1 (Keap1) were significantly increased (P<0.01). Compared with those in the model group, the level of TC, TG, LDL-C, ALT, and AST in serum and TG and NEFA in the liver of mice in the GPs-L, GPs-H, and SV groups were decreased, while the level of HDL-C in serum was significantly increased (P<0.05, P<0.01). The liver tissue structure and lipid deposition were improved. The levels of CoQ10 and GSH in serum and NADH in the liver were significantly increased, while the levels of MDA and Fe2+ in serum were significantly decreased (P<0.05, P<0.01). The mRNA and protein expressions of xCT, GPX4, p62, Nrf2, and FSP1 were significantly increased, while the mRNA and protein expressions of p53, SAT1, ALOX15, and Keap1 were significantly decreased (P<0.05, P<0.01). ConclusionGPs can interfere with liver lipid deposition in MAFLD mice through classical/non-classical ferroptosis pathways.
9.Effect of Gypenosides on MAFLD Mice and Its Molecular Mechanism Based on Classical/Non-classical Ferroptosis Pathways
Yu LIU ; Yupeng PEI ; Jiaxin WANG ; Jingxuan ZHU ; Xiaofei SUN ; Qun WANG ; Peng CUI ; Nan SONG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(17):99-107
ObjectiveTo explore the effect of gypenosides (GPs) on liver lipid deposition in metabolism-associated fatty liver disease (MAFLD) mice and its mechanism based on classical/non-classical ferroptosis. MethodsEight male C57BL/6 mice in a blank group and 32 male apolipoprotein E gene knockout (ApoE-/-) mice were randomly divided into a model group, a low-dose GPs (GPs-L) group, a high-dose GPs (GPs-H) group, and a simvastatin (SV) group. Starting from the second week, mice in the blank group were given a maintenance diet, and the other four groups were fed a high-fat diet daily. After eight weeks of feeding, mice in the GPs-L and GPs-H groups were given GPs of 1.487 mg·kg-1·d-1 and 2.973 mg·kg-1·d-1, respectively, and mice in the SV group were given simvastatin of 2.275 mg·kg-1·d-1. Mice in the blank group and the model group were given saline of equal volume by gavage for four weeks. The content of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in the serum of mice in each group was detected by an automatic biochemical analyzer. The level of non-esterified fatty acid (NEFA) and TG in the mouse liver was measured by the kit. The change in liver tissue structure and lipid deposition was observed by hematoxylin-eosin (HE) and oil red O staining. The levels of coenzyme Q10 (CoQ10), glutathione (GSH), malondialdehyde (MDA), and Fe2+ in serum, as well as nicotinamide adenine dinucleotide phosphate [NAD(P)H] in the liver were detected by enzyme-linked immunosorbent assay (ELISA). The expression of ferroptosis suppressor protein 1 (FSP1) in the liver of mice was observed by the immunohistochemical (IHC) method, and the expression of genes and proteins related to classical and non-classical ferroptosis pathways was analyzed by real-time polymerase chain reaction (Real-time PCR) and Wes automated protein expression analysis system. ResultsCompared with those in the blank group, the levels of TC, TG, LDL-C, ALT, and AST in serum and TG and NEFA in the liver in the model group were significantly increased, and the level of HDL-C in serum was significantly decreased (P<0.01). The liver tissue structure changed, and there were fat vacuoles of different sizes and a large number of red lipid droplets, with obvious lipid deposition. The level of CoQ10 and GSH in serum and NADH in the liver were significantly decreased, while the level of MDA and Fe2+ in serum was significantly increased (P<0.01). The mRNA and protein expressions of cystine/glutamate transporter (xCT/SLC7A11), glutathione peroxidase (GPX4), p62, nuclear factor E2-related factor 2 (Nrf2), and FSP1 were significantly decreased, and the mRNA and protein expressions of tumor antigen (p53), spermidine/spermine N1-acetyltransferase 1 (SAT1), arachidonate 15-lipoxygenase (ALOX15), and Kelch-like epichlorohydrin-associated protein-1 (Keap1) were significantly increased (P<0.01). Compared with those in the model group, the level of TC, TG, LDL-C, ALT, and AST in serum and TG and NEFA in the liver of mice in the GPs-L, GPs-H, and SV groups were decreased, while the level of HDL-C in serum was significantly increased (P<0.05, P<0.01). The liver tissue structure and lipid deposition were improved. The levels of CoQ10 and GSH in serum and NADH in the liver were significantly increased, while the levels of MDA and Fe2+ in serum were significantly decreased (P<0.05, P<0.01). The mRNA and protein expressions of xCT, GPX4, p62, Nrf2, and FSP1 were significantly increased, while the mRNA and protein expressions of p53, SAT1, ALOX15, and Keap1 were significantly decreased (P<0.05, P<0.01). ConclusionGPs can interfere with liver lipid deposition in MAFLD mice through classical/non-classical ferroptosis pathways.
10.Experience in the Application of Jiao (角) Medicine in Treating Diabetes Mellitus from the Perspective of Qi, Blood and Fluids
Jinhao HU ; Guiyan SUN ; He GAO ; Yufeng YANG ; Nan HU ; Yan SHI
Journal of Traditional Chinese Medicine 2025;66(16):1727-1730
This paper summarizes the clinical experience in applying jiao (角) medicine to treat diabetes mellitus from the perspective of qi, blood, and fluids. It is believed that impaired spleen transportation and transformation is the key pathomechanism of diabetes, leading to metabolic disturbances in qi, blood, and fluids, and resulting in a sequential pathological progression of "qi → thick fluids → thin fluids → blood". At the qi level, the disease is mainly characterized by spleen qi deficiency and stagnation, and is commonly treated with Hongshen (Panax Ginseng), Huangqi (Astragalus Mongholicus), and Baizhu (Atractylodes Macrocephala) to tonify the spleen and regulate qi. At the thick fluids level, the condition manifests as abdominal distension, internal heat, and turbid pathogens, requiring Zexie (Alisma Orientale), Huanglian (Coptis Chinensis), and Dahuang (Rheum Palmatum) to clear the spleen and drain turbidity. At the thin fluids level, with qi and yin deficiency and predominant yin damage, Gegen (Pueraria Lobata), Wuweizi (Schisandra Chinensis), and Maidong (Ophiopogon Japonicus) are used to nourish yin and generate fluids. At the blood level, where vascular damage is predominant, Shuizhifen (Whitmania Pigra Powder), Danshen (Salvia Miltiorrhiza), and Sanqifen (Panax Notoginseng Powder) are applied to activate blood circulation, resolve stasis, and unblock the channels. Clinicians may flexibly select appropriate jiao medicine based on the specific pathological layer affected in each patient.

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