1.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.
2.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.
3.Metabolomics Reveals Immune System Domage of Dictamnine
Xiaocan GAI ; Jiaxin RUAN ; Sujie LIU ; Chen WANG ; Xiaofan WANG ; Jiahe YAN ; Yu WANG ; Fang LU ; Shumin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(20):57-65
ObjectiveTo explore the mechanism of the immunotoxicity induced by dictamnine (DIC) in rats and the recovery effect after drug withdrawal by ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry, thereby providing a theoretical basis for elucidating the toxic mechanism of DIC. MethodsSD rats were randomized into blank (normal saline), DIC (10 mg·kg-1), and DIC withdrawal (recovery period) groups (n=8). The rats were continuously treated for 7 days, once a day, and the body weight and organ weight were recorded. The levels of interleukin-1 (IL-1), IL-6, and tumor necrosis factor-α (TNF-α) in the serum and immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM) in the spleen were determined by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to observe the pathological changes in the spleen. ultra performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was employed to screen the potential biomarkers of immune inflammation caused by DIC, and pathway enrichment analysis and correlation analysis were performed. The mRNA levels of IL-1β, TNF-α, lysophosphatidylcholine acyltransferase 2 (LPCAT2), and farnesoid X receptor (FXR) in the serum were determined by Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR). ResultsCompared with the blank group, the DIC group showed elevated levels of IL-1β, IL-6, and TNF-α in the serum (P<0.01), and the DIC withdrawal group showcased lowered levels of IL-1β, IL-6, and TNF-α in the serum (P<0.01). The levels of IgA, IgG, and IgM in the spleen of rats in the DIC group were decreased (P<0.01), while those in the DIC withdrawal group were recovered (P<0.05, P<0.01). Untargeted metabolomics of the serum and spleen screened out 14 common differential metabolites and 14 common metabolic pathways. The Spearman correlation analysis between differential metabolites and inflammatory factors identified PC (32∶0), LysoPC (20∶4/0∶0), LysoPC (P-18∶0/0∶0), taurochenodeoxycholic acid, taurocholic acid, LysoPC [20∶5(5Z,8Z,11Z,14Z,17Z)/0∶0], chenodeoxycholic acid, arachidonic acid, LysoPC (18∶0/0∶0), LysoPC (15∶0/0∶0), LysoPC (16∶0/0∶0), and LysoPC (17∶0/0∶0) as the biomarkers of immunotoxicity induced by DIC in SD rats. In the process of immunotoxicity caused by DIC, lipid metabolism disorders such as glycerophospholipid metabolism, primary bile acid metabolism, and arachidonic acid metabolism were enriched, which was consistent with the DIC-induced inflammatory factors and pathological characteristics of the spleen. Compared with the blank group, the DIC group exhibited up-regulated mRNA levels of IL-1β, TNF-α, LPCAT2, and FXR (P<0.01), and the up-regulation was decreased in the withdrawal group (P<0.01). ConclusionDIC can lead to immune and inflammatory disorders. DIC withdrawal can regulate the expression of biomarkers related to serum and spleen metabolites, regulate the inflammatory metabolic pathway, reduce the inflammation level, and alleviate the metabolic disorders, thus attenuating the potential toxicity induced by DIC.
4.Application of cognitive interview in the compilation of Family Resilience Scale for Schizophrenic Patients
Jiaxin REN ; Yu WANG ; Mengnan QIN ; Yuqiu ZHOU
Chinese Journal of Modern Nursing 2024;30(29):3945-3950
Objective:To assess the understanding level of Family Resilience Scale for Schizophrenic Patients among respondents using cognitive interviews and revise the items accordingly.Methods:Using the purposive sampling method, two cognitive interviews were conducted on schizophrenia patients admitted to Chifeng An Ding Hospital from April to June 2023. A Question Appraisal System (QAS-99) was used to encode the interview data to find the problems existing in the scale structure, and at the same time, the scale items were revised based on expert opinions.Results:The first round of cognitive interviews showed ten questions, mainly focusing on "clarification"questions. The results of the second round of cognitive interviews showed that all respondents could correctly understand the scale items revised by the first round of lognitive interviews, and no further revision was required. The final Family Resilience Scale for Schizophrenic Patients included 24 items.Conclusions:Cognitive interviews can help to find and solve the differences in the understanding of items between researchers and interviewees in the compilation of the Family Resilience Scale for Schizophrenic Patients so as to improve the accuracy and reliability of the scale.
5.Comparison and optimization of special staining methods for observation of myocardial fibrosis
Yaheng WANG ; Jiaxin MA ; Yu LEI ; Lianfeng ZHANG ; Dan LYU
Acta Laboratorium Animalis Scientia Sinica 2024;32(3):347-354
Objective The existing dyeing methods of myocardial fibrosis were optimized to make up for the problems of missing and misreading of collagen fibers in the quantitative analysis of the current common dyeing methods of myocardial fibers,and to provide a reference for the semi-quantitative and diagnosis of myocardial fibrosis.Methods Paraffin sections of cardiac tissue were prepared using a transgenic mouse model of cardiomyopathy with a specific laboratory-constructed cTnTR141W gene mutation.Four staining method were performed for comparative observations:Masson's trichrome(Masson)staining,picrosirius red(PSR)staining,van Gieson(VG)staining,and Sirius red/fast green(SR/FG)staining.Image J 2.1.0 software was used to quantitatively compare the areas of collagen fibers.SR/FG was optimized from three aspects:dye concentration,staining time,and acid solution prestaining,and the quantitative analysis of collagen fibers was then verified.Results The collagen fiber distribution was observed by the four staining method,among which SR/FG was notable.It involved prestaining with a 0.1%Sirius red-picric acid acidic solution for 5 min,adjusting the concentration of the dye solution to 0.1%Sirius red-picric acid and 0.04%fast green mixture,and incubating the sections in the mixed staining solution for 1 h.This method exhibited the lowest incidence of missed readings and loss in determining the proportion of collagen fibers.Conclusions Compared with other traditional collagen fiber staining method,the optimized SR/FG technique described in this paper produces bright coloring of collagen fibers and myocardial tissue,obvious color contrast,and high stability,convenience,and speed.It is suitable for subsequent quantitative analysis and determination of the collagen fiber proportion.
6.A qualitative study of perception of risk of relapse in patients with schizophrenia
Hong YU ; Yuqiu ZHOU ; Yujing SUN ; Guohua LI ; Dongyu HOU ; Mengnan QIN ; Jiaxin REN ; Weimiao ZHANG
Chinese Mental Health Journal 2024;38(5):388-393
Objective:To elucidate the primary elements pertaining to the perception of relapse risk and to in-vestigate the characteristics and alterations of perception of the risk of recurrence in patients with schizophrenia.Methods:By using the method of phenomenological study,semi-structured in-depth interviews were conducted among schizophrenic patients with first onset,first recurrence and multiple recurrences.Twenty-three 23 outpatient and inpatient cases that met the criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)were included,and all patients had PANSS scores below 60.The interview data were collated and analyzed according to Colaizzi analysis.Results:The perception of recurrence risk in patients with schizophrenia en-compassed 4 major themes and 11 sub-themes,namely susceptibility(limited overall understanding,transition from optimism to objectivity),detection of early warning symptoms(dynamic escalation,assistance from family mem-bers in identification),understanding risk factors(lack of understanding,the relationship between psychosocial fac-tors and relapse,dynamic understanding of medication-relapse relationship),and apprehension of the consequences of recurrence(care burden and financial constraints,impaired social functioning and maladjustment,impact on pub-lic safety,personal health risks).Conclusion:The content of risk perception of recurrence in patients with schizo-phrenia is relatively substantial.The overall level of risk perception of recurrence in patients with schizophrenia is low.
7.The role of TFEB activated by aerobic exercise on insulin resistance in skeletal muscle of high fat diet mice
Ping WANG ; Jiaxin LI ; Xiaolong CHEN ; Xin YU ; Xiaopeng JIN ; Minghua ZHU
Chinese Journal of Sports Medicine 2024;43(3):193-204
Objective To explore the role of transcription factor EB(TFEB)induced by aerobic exer-cise in improving insulin resistance(IR)of skeletal muscles in high-fat diet mice.Method Eighteen male SPF C57BL/6 mice aged 6 weeks were randomly divided into a common diet group(CON),a high-fat diet group(HFD),and a high-fat diet exercise group(HFDE),each of 6.Both high-fat groups were on high-fat diet for 12 weeks.Then the HFDE group underwent daily 60-minute tread-mill exercise with the slope of 0°,at a speed of 12 m/min,5 times per week for 12 weeks.Finally,the glucose tolerance and insulin sensitivity were detected using the intraperitoneal injection glucose tol-erance test(IPGTT)and intraperitoneal injection insulin tolerance test(IPITT).The fasting blood glu-cose and insulin contents were measured by biochemical method,and the IR level was calculated by using the homeostatic model assessment of insulin resistance(HOMA-IR).Moreover,Western blotting was employed to detect the expression of phosphorylated transcription factor EB(pTFEB)and TFEB in skeletal muscle,glucose transporter 4(GLUT4)in cytoplasm and membrane,phosphorylated insulin re-ceptor substrates1(pIRS1),phosphorylated protein kinase B(pAKT),phosphoinositide 3-kinase(PI3K),and phosphorylated akt substrate of 160 kD(pTBC1D4)in skeletal muscle.The correlation of pTFEB and TFEB to insulin signaling pathway-related proteins was analyzed.Results(1)Compared with the CON group,there was a significant increase in the average body weight,IPGTT,blood glucose at each time point of IPGTT,area under curve(AUC),serum insulin,HOMA-IR,protein expressions of pTFEB,total-TFEB and GLUT4 in cytoplasm of the HFD group(P<0.01),but a significant decrease in the average protein expressions of pIRS1,pAKT,PI3K,pTBC1D4 and GLUT4 in cell membrane of skeletal muscles(P<0.01).However,no significant differences were found between the two groups in the average expression of pTFEB and T-TFEB proteins.(2)Compared to the HFD group,a signifi-cant increase was found in the average body weight,blood glucose at each time point of IPGTT,blood glucose of IPITT at 0 min,30 min and 60 min and AUC,serum insulin,HOMA-IR,expres-sions of pTFEB,T-TFEB and GLUT4 in cytoplasm of HFDE group(P<0.05 or P<0.01),with a signifi-cant decrease in the average protein expressions of pIRS1,pAKT,PI3K,pTBC1D4 and GLUT4 in cell membrane and T-TFEB in nucleus(P<0.01).(3)TFEB was negatively correlated with the expres-sion of pIRS1,PI3K,pAKT,and pTBC1D4 proteins(r=-0.8642,r=-0.7789,r=-0.8946,r=-0.8040)but positively correlated with cytoplasmic GLUT4(r=0.8532,P<0.01).Moreover,TFEB in the nucleus was of positive correlation with GLUT4 in the cell membrane(r=0.7744,P<0.01).Conclusions High-fat diet can decrease the expression of insulin signaling pathway related proteins in skeletal mus-cles of mice and weaken their insulin action,leading to the disorder of glucose and lipid metabolism.However,aerobic exercise can significantly increase the expression of such proteins to promote insulin function and sensitivity,and relieve disorders in glucose and lipid metabolism.This effect may be achieved through the promotion of skeletal muscle TFEB nuclear translocation,which activates IRS1/PI3K/AKT/TBC1D4/GLUT4 signaling pathway and facilitates GLUT4 membrane translocation,ultimately enhancing glucose uptake in skeletal muscle cells.The authors speculate that the TFEB-mediated insu-lin signaling pathway may be an important molecular pathway for aerobic exercise to improve insulin re-sistance.
8.Research progress of pachychoroid spectrum disorders
Xianhui ZHOU ; Jiaxin PENG ; Wenqian DENG ; Juan YU
Chinese Journal of Ocular Fundus Diseases 2024;40(10):803-807
The pachychoroid spectrum disorders (PSD) refers to a group of clinical disorders characterized by common features of pathological choroidal thickening and potential pathogenic mechanisms. The pathological mechanism of PSD is very complex, and the theory of venous overload provides valuable research directions. The multimodal imaging technology represented by optical coherence tomography angiography has continuously evolved to provide clear and three-dimensional images of the fundus, making it easier to diagnose and monitor PSD at an early stage. There is no unified consensus on how to develop a treatment plan for PSD, and current research has shown that feasible treatments include drug therapy, laser photocoagulation therapy, and photodynamic therapy. However, the evidence of effectiveness and safety provided by these studies is still not sufficient. Surgery and integrative Chinese and Western medicine may provide new prospects for the treatment of PSD. In the future, it is necessary to further develop reasonable research programs, expand the sample size, strengthen follow-up observation, and provide more safe and effective treatment programs for patients.
9.The effectiveness of internet-based decision aids in colorectal cancer screening:A systematic review
Qian LIAO ; Yufeng YU ; Ting YAO ; Jiaxin LI ; Wei ZHOU
China Modern Doctor 2024;62(16):51-56
Objective To evaluate the effectiveness of internet-based decision aids(DA)in colorectal cancer screening.Methods Randomized controlled trials of efficacy of internet-based DA in colorectal cancer screening were searched by computer from CNKI,Wanfang Data,VIP,CBM,PubMed,the Cochrane Library,Embase and Web of Science.The retrieval period was from the establishment of the database to June 2023.Descriptive analysis was used to analyze the main contents and summarize their clinical application effects.Results A total of 12 literatures were included,including 6038 subjects,of which 3089 were in experimental group and 2949 were in control group.The results showed that the contents of internet-based DA mainly included basic information support,benefits and risks of colorectal cancer screening,and clarification of patients'personal values.It could help patients enhance screening willingness,improve informed decision-making ability,reduce decision-making conflicts,and promote the positive role of patients in decision-making.Patients have higher satisfaction with internet-based DA.Conclusion Internet-based DA has shown positive results in the application of colorectal cancer screening,and has unique advantages over the traditional paper version of the manual,but it still has certain limitations.In the future,we can learn from the relevant theoretical achievements of foreign decision-making assistance,research and develop a more comprehensive DA for colorectal cancer screening combined with China's national conditions.
10.Applications and Prospect of Diagnostic Radionuclide
Jiaxin DING ; Zhuoling RAN ; Yuxian ZHANG ; Ran ZHANG ; Lin YU ; Liping YANG ; Yuanqing NING ; Xu GAO ; Minghui AN ; Jing XIE ; Dong CHAI ; Jian GONG
Herald of Medicine 2024;43(10):1609-1614
Nuclear medicine plays an indispensable role in the diagnosis,treatment,and prognosis of a wide range of diseases.Nuclear medicine using radionuclides for diagnosis has the advantages of accuracy,speed,high sensitivity and high resolution.Currently,several radionuclides play pivotal roles in disease diagnosis.This article primarily examines the clinical application and research of diagnostic radionuclides,including 18 F,89 Zr,68 Ga,99m Tc,131 I,123 I,and 11 C.The objective is to offer valuable insights for disease diagnosis and staging of diseases.

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