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.Comparative study of retinal volume changes in ischemic and non-ischemic macular edema secondary to branch retinal vein occlusion treated with ranib-izumab
Zhen XING ; Shuna WANG ; Yan SUN ; Yupeng ZHANG ; Xiuming XING ; Kaili YANG ; Jun ZHAO
Recent Advances in Ophthalmology 2024;44(3):217-222
Objective To compare the clinical outcomes and retinal volume changes in patients with ischemic and non-ischemic macular edema secondary to branch retinal vein occlusion(BRVO-ME)using optical coherence tomography angiography(OCTA).Methods The clinical data of 34 ischemic BRVO-ME patients(34 eyes,ischemic group)and 21 non-ischemic BRVO-ME patients(21 eyes,non-ischemic group)were retrospectively analyzed.Patients in both groups re-ceived intravitreal injections of ranibizumab.The best corrected visual acuity(BCVA)and retinal volume of the macular ar-ea were assessed before,1 day,1 week,1 month,3 months and 6 months after the treatment.Results The BCVA(log-MAR)at 1 day after the treatment was 0.63±0.37 in the ischemic group and 0.44±0.22 in the non-ischemic group,and the difference was statistically significant(P=0.017).The retinal volumes of the outer retina,the full retina,and the Farafovea and Perifovea subdivisions of the full retina before the treatment were(6.42±1.90)mm3,(8.75±1.82)mm3,(3.20±0.87)mm3 and(5.10±0.89)mm3 in the ischemic group and(5.52±1.57)mm3,(7.83±1.56)mm3,(2.80± 0.71)mm3,and(4.66±0.77)mm3 in the non-ischemic group,respectively;1 day after treatment,they were(4.97± 1.18)mm3,(7.46±1.47)mm3,(2.62±0.60)mm3 and(4.53±0.80)mm3 in the ischemic group and(4.25±0.48)mm3,(6.58±0.56)mm3,(2.26±0.26)mm3 and(4.06±0.40)mm3 in the non-ischemic group,respectively;at 1 week after the treatment,they were(4.40±0.82)mm3,(6.90±0.85)mm3,(2.38±0.36)mm3 and(4.24±0.49)mm3 in the ischemic group and(4.04±0.35)mm3,(6.33±0.49)mm3,(2.15±0.19)mm3 and(3.95±0.35)mm3 in the non-ische-mic group,respectively,and the differences between the two groups were statistically significant(all P<0.05).The a-mount of retinal volume change from baseline in the outer retina and the full retina was(-2.48±2.38)mm3 and(-2.54±2.38)mm3 in the ischemic group,and(-1.31±1.58)mm3 and(-1.38±1.58)mm3 in the non-ischemic group at 1 month after treatment,respectively,and the differences between the two groups were statistically significant(both P<0.05).Conclusion Ranibizumab is effective in treating both ischemic and non-ischemic BRVO-ME.The short-term visu-al prognosis is better in the non-ischemic group than the ischemic group,and the retinal volume is higher in the ischemic group than the non-ischemic group.However,no significant difference is observed in the visual prognosis or retinal volume between the two groups after long-term treatment.
4.A novel nomogram-based model to predict the postoperative overall survival in patients with gastric and colorectal cancer
Siwen WANG ; Kangjing XU ; Xuejin GAO ; Tingting GAO ; Guangming SUN ; Yaqin XIAO ; Haoyang WANG ; Chenghao ZENG ; Deshuai SONG ; Yupeng ZHANG ; Lingli HUANG ; Bo LIAN ; Jianjiao CHEN ; Dong GUO ; Zhenyi JIA ; Yong WANG ; Fangyou GONG ; Junde ZHOU ; Zhigang XUE ; Zhida CHEN ; Gang LI ; Mengbin LI ; Wei ZHAO ; Yanbing ZHOU ; Huanlong QIN ; Xiaoting WU ; Kunhua WANG ; Qiang CHI ; Jianchun YU ; Yun TANG ; Guoli LI ; Li ZHANG ; Xinying WANG
Chinese Journal of Clinical Nutrition 2024;32(3):138-149
Objective:We aimed to develop a novel visualized model based on nomogram to predict postoperative overall survival.Methods:This was a multicenter, retrospective, observational cohort study, including participants with histologically confirmed gastric and colorectal cancer who underwent radical surgery from 11 medical centers in China from August 1, 2015 to June 30, 2018. Baseline characteristics, histopathological data and nutritional status, as assessed using Nutrition Risk Screening 2002 (NRS 2002) score and the scored Patient-Generated Subjective Global Assessment, were collected. The least absolute shrinkage and selection operator regression and Cox regression were used to identify variables to be included in the predictive model. Internal and external validations were performed.Results:There were 681 and 127 patients in the training and validation cohorts, respectively. A total of 188 deaths were observed over a median follow-up period of 59 (range: 58 to 60) months. Two independent predictors of NRS 2002 and Tumor-Node-Metastasis (TNM) stage were identified and incorporated into the prediction nomogram model together with the factor of age. The model's concordance index for 1-, 3- and 5-year overall survival was 0.696, 0.724, and 0.738 in the training cohort and 0.801, 0.812, and 0.793 in the validation cohort, respectively.Conclusions:In this study, a new nomogram prediction model based on NRS 2002 score was developed and validated for predicting the overall postoperative survival of patients with gastric colorectal cancer. This model has good differentiation, calibration and clinical practicability in predicting the long-term survival rate of patients with gastrointestinal cancer after radical surgery.
5.Effects of sinomenine on LPS-induced apoptosis and autophagy of lung epithelial cells in JNK/c-Jun signaling pathway
Li LI ; Yingying SUN ; Ying BAI ; Luowen HU ; Qingqing WEI ; Yupeng YAN ; Ji WANG
Chinese Journal of Immunology 2024;40(4):731-735
Objective:To explore the effect of sinomenine(SIN)on LPS-induced apoptosis and autophagy of lung epithelial cells through the JNK/c-Jun signaling pathway.Methods:MLE-12 lung epithelial cells were cultured,and the toxicity of SIN was detected by CCK-8.Apoptosis was detected by flow cytometry,the number of autophagosomes was detected by immunofluorescence,and the expression levels of apoptosis,autophagy and JNK/c-Jun signaling pathway-related proteins were detected by Western blot.Results:After LPS modeling,apoptosis rate and the number of autophagosomes were increased,the protein levels of Cleaved caspase-3,Bax,and Beclin-1,and LC3Ⅱ/LC3Ⅰ,p-JNK/JNK and p-c-Jun/c-Jun were increased(P<0.05);Bcl-2 and P62 protein levels were decreased(P<0.05).SIN treatment can significantly improve the effects of LPS on apoptosis and autophagy,as well as the regulation of the JNK/c-Jun signaling pathway(P<0.05).Treatment with the autophagy inhibitor 3-MA or the JNK agonist ANISO could partially reverse the protective effect of SIN on LPS-induced lung epithelial cells(P<0.05).Conclusion:SIN may increase autophagy and pro-tect lung epithelial cells damaged by LPS by regulating proteins related to the JNK/c-Jun signaling pathway.
6.The value of parathyroid autotransplantation in endoscopic radical operation for thyroid carcinoma
Qi ZHANG ; Tingbao CAO ; Yupeng ZHANG ; An SUN ; Runhong WANG ; Tongying YI ; Kunpeng QU
Chinese Journal of General Surgery 2024;39(8):598-603
Objective:To evaluate the effects of parathyroid autotransplantation on total central lymph node dissection and postoperative parathyroid functional recovery in endoscopic radical operation for thyroid carcinoma.Method:The data of 152 patients undergoing endoscopic radical operation for thyroid carcinoma are retrospectively analyzed. The incidence of postoperative hypoparathyroidism, serum PTH and Ca 2+ concentrations at different time points, and the number of lymph nodes cleared were counted. Results:The rate of temporary hypoparathyroidism in the experimental group was higher than that in the control group, and the incidence of permanent hypoparathyroidism was lower than that in the control group, with statistically significant differences ( χ2=6.243, P=0.029). Patient's PTH in the experimental group is significantly higher than that in the control group at 1 week, 1 , 3 , 6 and 12 months after operation, and the difference is statistically significant ( F=25.193, P<0.05); Ca 2+ concentration in experimental group is higher than that in control group at 1, 3, 6 and 12 months after operation, and the difference is statistically significant ( F=3.268, P=0.005); The average number of central zone lymph node dissection and positive lymph nodes per case in the experimental group was higher than that in the control group, and the difference was statistically significant ( t=2.000, P=0.047; t=2.014, P=0.046). Conclusion:In radical lumpectomy for thyroid cancer, parathyroid autotransplantation can effectively prevent permanent postoperative hypoparathyroidism while achieving a more complete lymph node dissection in the central region.
7.Association between serum uric acid concentration and radiographic axial spondylarthritis: a cross-sectional study of 202 patients.
Yupeng LAI ; Yanpeng ZHANG ; Zhihao LEI ; Yihong HUANG ; Tongxin NI ; Pin HE ; Xiaoling LI ; Chiduo XU ; Jun XIA ; Meiying WANG
Chinese Medical Journal 2023;136(9):1114-1116
8.Drug resistance and virulence characteristics of of Staphylococcus aureus isolated from skin sites of suppurative infections in Inner Mongolia
Jianlin SUN ; Yang ZHANG ; Yupeng ZHANG ; Xinxiang LYU ; Junrui WANG
Chinese Journal of Dermatology 2022;55(3):200-207
Objective:To analyze drug resistance, virulence and molecular epidemiological characteristics of Staphylococcus aureus ( S. aureus) isolated from skin sites of suppurative infections, and to provide an experimental basis for clinical anti-infective therapies. Methods:Swab samples from suppurative skin lesions and nasal secretions were collected from inpatients in Department of Dermatology, the Affiliated Hospital of Inner Mongolia Medical University from May 2020 to December 2020, and subjected to bacterial isolation and culture. Suspected S. aureus colonies were identified by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. Drug sensitivity test was conducted by using the broth microdilution method. Virulence genes of S. aureus were amplified by PCR, and real-time fluorescence-based quantitative PCR was performed to determine the relative expression of 4 virulence genes including tsst-1, pvl, hla and clfA in S. aureus strains from different sources. S. aureus strains were genotyped by multilocus sequence typing. Drug resistance rates and detection rates of virulence genes were compared by using chi-square test or Fisher′s exact test, and measurement data among groups were compared by using t test or Mann-Whitney U test. Results:A total of 85 strains of S. aureus were isolated from 210 inpatients, including 54 isolates from skin sites of suppurative infections (case group) and 31 isolates from the nasal cavity (control group) . Drug sensitivity test showed that 14 strains of methicillin-resistant S. aureus (MRSA) were identified among 85 strains of S. aureus. The resistance rate to penicillin was the highest (90.59%, 77/85) in the 85 S. aureus strains; the resistance rates to clindamycin and erythromycin were 60.00% (51/85) and 61.18% (52/85) respectively; no strains showed resistance to rifampicin, vancomycin or linezolid. PCR showed that the detection rate of the pvl gene was 33.33% (18/54) in the case group, which was significantly higher than that in the control group (12.90%, 4/31; χ2= 4.28, P= 0.038) . Real-time fluorescence-based quantitative PCR showed that the relative expression level of the clfA gene was significantly higher in the control group (3.87[2.30, 5.94]) than in the case group (1.63[0.95, 2.62], P= 0.007) . A total of 17 ST types were identified among the 85 strains of S. aureus, and the dominant types were ST398-methicillin-susceptible S. aureus (20/71) and ST22-MRSA (9/14) . The detection rate of the virulence gene pvl was significantly higher in the ST22-MRSA strain (14/14) than in the non-ST22 MRSA strains (0, P < 0.001) . Conclusions:S. aureus strains isolated from the skin sites of suppurative infections were highly resistant to penicillin, clindamycin and erythromycin, so these antibiotics should not be used as the first-choice empiric treatment. The occurrence of cutaneous S. aureus infections may be associated with the virulence gene pvl, and the nasal colonization of S. aureus may be associated with the clfA gene.
9.Serialized treatment system for microtia
Leren HE ; Haiyue JIANG ; Qinghua YANG ; Yanyong ZHAO ; Bo PAN ; Lin LIN ; Yupeng SONG ; Hengyun SUN ; Xiaobo YU ; Jiayu ZHOU
Chinese Journal of Plastic Surgery 2022;38(7):725-729
As for the treatment of microtia, the status quo is as follows. The ear reconstruction with autologous costal cartilage has been generally accepted as the therapeutic strategy for type Ⅲ/Ⅳ patients with only small ear lobe remaining or complete absence of auricle, and the outcomes are improved steadily with the advances in technology; but for type Ⅰ/Ⅱ patients with larger remnant ear, there is insufficient evidence to be able to support any specific treatment methods as the potential unified approach for surgeons to choose from. Non-surgical treatment with appliance wearing may play an auxiliary role in the treatment of microtia, which is worthy of further research. The authors proposed a serialized treatment system based on their clinical practice and literature review. It is expected to be helpful for the treatment of microtia.
10.Serialized treatment system for microtia
Leren HE ; Haiyue JIANG ; Qinghua YANG ; Yanyong ZHAO ; Bo PAN ; Lin LIN ; Yupeng SONG ; Hengyun SUN ; Xiaobo YU ; Jiayu ZHOU
Chinese Journal of Plastic Surgery 2022;38(7):725-729
As for the treatment of microtia, the status quo is as follows. The ear reconstruction with autologous costal cartilage has been generally accepted as the therapeutic strategy for type Ⅲ/Ⅳ patients with only small ear lobe remaining or complete absence of auricle, and the outcomes are improved steadily with the advances in technology; but for type Ⅰ/Ⅱ patients with larger remnant ear, there is insufficient evidence to be able to support any specific treatment methods as the potential unified approach for surgeons to choose from. Non-surgical treatment with appliance wearing may play an auxiliary role in the treatment of microtia, which is worthy of further research. The authors proposed a serialized treatment system based on their clinical practice and literature review. It is expected to be helpful for the treatment of microtia.

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