1.Bioinformatics Reveals Mechanism of Schisandrin B in Inhibiting Ferroptosis to Ameliorate Methionine and Choline Deficiency-induced Fatty Liver Disease in Mice
Zhifeng ZHU ; Wenting LI ; Yongjun CAO ; Yuanyuan LIN ; Yifei LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):74-83
ObjectiveNonalcoholic fatty liver disease (NAFLD) is a metabolic stress liver injury. Ferroptosis is involved in the occurrence and development of NAFLD. Exploring the efficacy and mechanism of schisandrin B in treating NAFLD facilitates the development of strategies for the prevention and treatment of NAFLD. MethodsThe molecular structure of schisandrin B was obtained by searching against PubChem, and the related targets were predicted by SwissTargetPrediction. The active ingredients and their targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and the high-throughput experiment- and reference-guide database of traditional Chinese medicine (HERB). GeneCards and FerrDb were searched for the targets of NAFLD and ferroptosis. The common targets were taken as the core targets, and the protein-protein interaction network of the core targets was established. DAVID was used for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Finally, molecular docking was performed between schisandrin B and core targets, and the binding energy was calculated. C57BL/6 mice were fed with a methionine and choline-deficiency (MCD) diet for the modeling of NAFLD. Mice were randomized into normal, model, positive drug (essentiale), and low- and high-dose schisandrin B groups. The body mass and liver index of mice were measured after drug administration. The levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum and those of total cholesterol (TC), triglyceride (TG), malondialdehyde (MDA), glutathione (GSH), and Fe2+ in the liver homogenate were measured by biochemical assay kits. The pathological changes of the liver tissue were observed by hematoxylin-eosin (HE) and red oil O staining. Enzyme-linked immunosorbent assay was employed to determine the levels of interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α, and 4-hydroxynonenal (4-HNE) in the serum. Western blotting and real-time PCR were employed to determine the protein and mRNA levels, respectively, of solute carrier family 7 member 11 (SLC7A11), solute carrier family 3 member 2 (SLC3A2), glutathione peroxidase 4 (GPX4), transferrin, and ferritin heavy chain (FTH) in the liver tissue. ResultsA total of 2 370, 2 547, and 1 451 targets of schisandrin B, NAFLD, and ferroptosis were obtained, in which 90 common targets were shared by the three. Enrichment analyses predicted 505 GO terms and 92 KEGG pathways. Molecular docking suggested that schizandrin B had strong binding affinity with the key targets of ferropstosis (SLC7A11 and SLC3A2). Animal experiments showed that schizandrin B significantly decreased the liver index, lowered the levels of ALT, AST, TC, TG, IL-6, IL-1β, and TNF-α, alleviated hepatocyte ballooning and inflammatory cell infiltration, and reduced lipid accumulation in the liver of NAFLD mice. In addition, schisandrin B significantly lowered the levels of MDA, 4-HNE, and Fe2+, elevated the level of GSH, up-regulated the protein and mRNA levels of SLC7A11, SLC3A2, and GPX4, and down-regulated the protein and mRNA levels of transferrin in the liver tissue. ConclusionSchisandrin B can alleviate NAFLD by inhibiting ferroptosis in hepatocytes.
2.The characteristics and mechanism of dynamic changes of different components in microenvironment in regulating the progression of liver fibrosis
Huilan ZHAO ; Zongxu LIU ; Shumin LI ; Zhifeng WANG ; Minghui LIU ; Qian SHENG ; Kunbin KE ; Xinan SHI
Journal of Clinical Hepatology 2025;41(4):755-760
The liver has diverse functions such as metabolism, detoxification, and immune defense, and the maintenance of hepatic microenvironment homeostasis is crucial for overall bodily health. The hepatic microenvironment consists of the components such as parenchymal cells, non-parenchymal cells, and non-cellular components. Chronic inflammatory responses induced by various etiological factors may promote the formation and progression of liver fibrosis. During the dynamic progression of liver fibrosis, from the early to advanced stages, various components within the hepatic microenvironment undergo a series of changes, which can promote the malignant progression of liver fibrosis. An in-depth exploration of the mechanisms underlying such changes in each component of the liver fibrosis microenvironment is of great significance for understanding the pathogenesis of liver fibrosis and discovering potential treatment strategies.
3.Research progress on epigenetic changes induced by ionizing radiation
WANG Suyi ; SONG Li ; LIU Zhifeng ; JIANG Rongyue ; SONG Yue ; XIA Lu ; YANG Fan
Journal of Preventive Medicine 2025;37(4):361-364
Ionizing radiation (IR) is a genotoxic agent that can play an important role in the occurrence and development of various diseases by inducing epigenetic changes. Studies have shown that the basic mechanisms of IR-induced epigenetic changes include abnormal DNA methylation, increased oxidative stress levels, changes in histone modifications, and regulation by microRNAs. These can lead to health hazards such as malignant tumors, genetic effects, nervous system damage, circulatory system diseases, and radiation-induced cataracts. This article collected relevant literatures regarding epigenetic changes induced by IR from 2005 to 2024, and reviewed the basic mechanisms of IR-induced epigenetic changes and the associated disease risks, providing the reference for radiation protection in occupational exposure and radiotherapy.
4.Thirteen serum biochemical indexes and five whole blood coagulation indices in a point-of-care testing analyzer: ideal protocol for evaluating pulmonary and critical care medicine.
Mingtao LIU ; Li LIU ; Jiaxi CHEN ; Zhifeng HUANG ; Huiqing ZHU ; Shengxuan LIN ; Weitian QI ; Zhangkai J CHENG ; Ning LI ; Baoqing SUN
Journal of Zhejiang University. Science. B 2025;26(2):158-171
The accurate and timely detection of biochemical coagulation indicators is pivotal in pulmonary and critical care medicine. Despite their reliability, traditional laboratories often lag in terms of rapid diagnosis. Point-of-care testing (POCT) has emerged as a promising alternative, which is awaiting rigorous validation. We assessed 226 samples from patients at the First Affiliated Hospital of Guangzhou Medical University using a Beckman Coulter AU5821 and a PUSHKANG POCT Biochemistry Analyzer MS100. Furthermore, 350 samples were evaluated with a Stago coagulation analyzer STAR MAX and a PUSHKANG POCT Coagulation Analyzer MC100. Metrics included thirteen biochemical indexes, such as albumin, and five coagulation indices, such as prothrombin time. Comparisons were drawn against the PUSHKANG POCT analyzer. Bland-Altman plots (MS100: 0.8206‒0.9995; MC100: 0.8318‒0.9911) evinced significant consistency between methodologies. Spearman correlation pinpointed a potent linear association between conventional devices and the PUSHKANG POCT analyzer, further underscored by a robust correlation coefficient (MS100: 0.713‒0.949; MC100: 0.593‒0.950). The PUSHKANG POCT was validated as a dependable tool for serum and whole blood biochemical and coagulation diagnostics. This emphasizes its prospective clinical efficacy, offering clinicians a swift diagnostic tool and heralding a new era of enhanced patient care outcomes.
Humans
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Point-of-Care Testing
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Critical Care
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Blood Coagulation Tests/methods*
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Male
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Blood Coagulation
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Female
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Middle Aged
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Reproducibility of Results
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Prothrombin Time
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Aged
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Adult
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Point-of-Care Systems
5.Mechanistic insights into “Three Methods and Three Acupoints” Tuina therapy for improving spinal microcirculation and motor function in sciatic nerve injury model rats
Hanyu Zhang ; Yingqi Zhang ; Hourong Wang ; Jiayue Liu ; Jiawei Sun ; Jinping Chen ; Zhifeng Liu ; Tianyuan Yu ; Jian Shu
Journal of Traditional Chinese Medical Sciences 2025;2025(1):125-134
Objective:
To investigate the effects of “Three Methods and Three Acupoints” (TMTP) Tuina therapy on spinal microcirculation in sciatic nerve injury (SNI).
Methods:
Thirty-six Sprague–Dawley rats were randomly assigned to four groups: normal, sham operation, model, and TMTP Tuina. Successful model induction was confirmed by observable hind limb lameness. After 20 sessions, hind limb grip strength and motor nerve conduction velocity (MNCV) were measured at baseline and following the 10th and 20th intervention. CD31 and α-SMA in the ventral horn of SNI model rats were detected using immunofluorescence. Motor neurons in the ventral horn were detected by Nissl staining. PTEN levels in the ventral horn were measured by ELISA, and PI3K, Akt, BDNF, VEGF, and HIF-1α expression was determined by RT-PCR. Spinal cord microcirculation was evaluated by western blotting analysis of the levels of Akt, p-Akt, BDNF, and VEGF.
Results:
Hind limb grip strength and MNCV significantly improved in the TMTP Tuina group compared to the model group (both P < .001). Morphology of ventral horn motor neurons in the TMTP Tuina group improved compared to the model group, with increased expressions of α-SMA (P = .002) and CD31 (P = .006). Western blot analysis indicated increased expression of VEGF (P = .005), p-Akt (P < .001), and BDNF (P = .008) in the ventral horn following Tuina treatment. RT-PCR analysis revealed increased expression of PI3K, Akt, BDNF, VEGF and HIF-1α (all P < .05). In contrast, expression of PTEN decreased compared to the model group (P < .001).
Conclusion
TMTP Tuina therapy may restore motor function in rats, enhance ventral horn motor neuron morphology, and promote angiogenesis and vascular smooth muscle proliferation. The mechanism may involve the activation of the PI3K/Akt signaling pathway.
6.A study on quantification assessment of segmental volume after thigh liposuction with three-dimensional scanning technology
Yifei LI ; Zhifeng LI ; Yunpeng GU ; Yicheng LIU ; Qianwen LYU ; Jingjing SUN ; Yue QI ; Guie MA
Chinese Journal of Plastic Surgery 2024;40(6):597-604
Objective:To investigate the quantification assessment of segmental volume after thigh liposuction utilizing three-dimensional(3D) scanning technology.Methods:This retrospective study was performed with the analysis of 3D scanning images of patients who had undergone bilateral thigh liposuction in Body Contouring & Fat Grafting Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences from January 2018 to September 2022. Preoperative and postoperative 3D scanning were performed to build visual 3D models of bilateral thighs. From top to the bottom, bilateral thighs were segmented into seven sections with a space of 5 cm in acquired 3D model. Certain measurements and calculation of preoperative and postoperative volume and volume change rate of the overall thigh and each segment were conducted, to validate the efficiency of liposuction (EOL). Additionally, EOL of each thigh segment was computed and the symmetry of bilateral thighs was analyzed before and after surgery. The volume differences were computed using the paired Wilcoxon rank-sum test, and intraclass correlation coefficient (ICC) was exerted to assess the symmetry of bilateral thighs before and after surgery.Results:A total of 36 female patients were included in the study, with an age range of 18 to 49 years and a mean age of (28.6±7.6) years. Follow-up duration ranged from 23 to 1 133 days postoperatively, with a mean follow-up period of 274.7 days. The results of 3D scanning measurements indicated significant changes ( P<0.01) in both the overall volume of the thigh and the volumes of each segment before and after surgery. The highest volume change rate and EOL were observed in the uppermost segment, and the volumetric change rate and EOL exhibited a descending trend across the segments of the thigh from the uppermost to the lowermost segments. The ICC of the volume of each segment consistently surpassed 0.950 whether preoperatively or postoperatively, indicating a high level of symmetry between the bilateral thighs, and the ICC of overall volume showed a notable increase from 0.992 preoperatively to 0.997 postoperatively. Conclusion:3D scanning technology can be exerted to quantify the volume changes before and after thigh liposuction. This study provided quantitative and objective evidence to confirm the efficacy of thigh liposuction procedure, elucidating that the most significant liposuction effects observed in the uppermost segment of the thigh. Moreover, postoperative assessments reveal a further enhancement in bilateral thigh symmetry.
7.A study on quantification assessment of segmental volume after thigh liposuction with three-dimensional scanning technology
Yifei LI ; Zhifeng LI ; Yunpeng GU ; Yicheng LIU ; Qianwen LYU ; Jingjing SUN ; Yue QI ; Guie MA
Chinese Journal of Plastic Surgery 2024;40(6):597-604
Objective:To investigate the quantification assessment of segmental volume after thigh liposuction utilizing three-dimensional(3D) scanning technology.Methods:This retrospective study was performed with the analysis of 3D scanning images of patients who had undergone bilateral thigh liposuction in Body Contouring & Fat Grafting Center, Plastic Surgery Hospital, Chinese Academy of Medical Sciences from January 2018 to September 2022. Preoperative and postoperative 3D scanning were performed to build visual 3D models of bilateral thighs. From top to the bottom, bilateral thighs were segmented into seven sections with a space of 5 cm in acquired 3D model. Certain measurements and calculation of preoperative and postoperative volume and volume change rate of the overall thigh and each segment were conducted, to validate the efficiency of liposuction (EOL). Additionally, EOL of each thigh segment was computed and the symmetry of bilateral thighs was analyzed before and after surgery. The volume differences were computed using the paired Wilcoxon rank-sum test, and intraclass correlation coefficient (ICC) was exerted to assess the symmetry of bilateral thighs before and after surgery.Results:A total of 36 female patients were included in the study, with an age range of 18 to 49 years and a mean age of (28.6±7.6) years. Follow-up duration ranged from 23 to 1 133 days postoperatively, with a mean follow-up period of 274.7 days. The results of 3D scanning measurements indicated significant changes ( P<0.01) in both the overall volume of the thigh and the volumes of each segment before and after surgery. The highest volume change rate and EOL were observed in the uppermost segment, and the volumetric change rate and EOL exhibited a descending trend across the segments of the thigh from the uppermost to the lowermost segments. The ICC of the volume of each segment consistently surpassed 0.950 whether preoperatively or postoperatively, indicating a high level of symmetry between the bilateral thighs, and the ICC of overall volume showed a notable increase from 0.992 preoperatively to 0.997 postoperatively. Conclusion:3D scanning technology can be exerted to quantify the volume changes before and after thigh liposuction. This study provided quantitative and objective evidence to confirm the efficacy of thigh liposuction procedure, elucidating that the most significant liposuction effects observed in the uppermost segment of the thigh. Moreover, postoperative assessments reveal a further enhancement in bilateral thigh symmetry.
8.Modification with IL-21 and CCL19 enhances killing efficiency and tumor infiltration of NKP30 CAR-T cells in lung cancer
Zhifeng ZHOU ; Shuoyan LIU ; Jieyu LI ; Mingqiu CHEN ; Hui LIN ; Yujie CHEN ; Weijie CHEN ; Junpeng LIN ; Hang ZHOU ; Qinfeng ZHENG
Journal of Southern Medical University 2024;44(10):1926-1936
Objective To investigate whether modification with IL-21 and CCL19 enhances killing and tumor-infiltrating efficiency of NKP30 CAR-T cells in lung cancer.Methods The modified IL-21-CCL19 NKP30 CAR-T cells expressing IL-21 and CCL19 fusion gene was constructed based on NKP30 CAR-T cells and stimulated with CD3CD28 antibodies and IL-2.The immunophenotype and migration of the cells in the presence of IL-21 were investigated using flow cytometry and migration experiments.Lactate dehydrogenase(LDH)release and sphere formation assays were used to assess the killing and infiltration capabilities of CAR-T cells,and the secretion levels of IFN-γ,IL-21 and CCL19 were determined with enzyme-linked immunospot assay(ELISPOT)and ELISA.A zebrafish model bearing HCG-27 cell xenograft was established by microinjection of the tumor cells into the yolk sac followed 24 h later by injection of the immune cells at the same site,and the fluorescence signals were captured using a fluorescent microscopy.Results The NKP30 ligand B7H6,which was almost undetectable in normal tissues and blood cells,was highly expressed(over 90%)in lung cancer cells.Compared with NKP30 CAR-T cells and conventional T cells,IL-21-CCL19 NKP30 CAR-T cells exhibited stronger proliferative and migration capabilities with the formation of central memory T cells.The reduced expressions of CTLA4 and PD1 in the constructed cells resulted in enhanced killing efficiency against lung cancer cells accompanied by significantly increased production of IFN-γ,IL-21 and CCL19.In the zebrafish models,CAR-T cells exhibited stronger cytotoxicity and proliferative abilities than typical T cells,but these differences were not statistically significant between the two CAR-T cells.Conclusion Modification of NKP30 CAR-T cells with IL-21 and CCL19 facilitates their access into solid tumors for more effective tumor cell killing while producing a large number of memory T cells.
9.Monitoring results of SARS-CoV-2 in urban sewage in Chongqing city in 2023
Gaomin LIU ; Jiqin ZHENG ; Yao CHEN ; Wenge TANG ; Zhifeng LI ; Shujun NIE
Chinese Journal of Experimental and Clinical Virology 2024;38(3):294-298
Objective:To offset the shortage of traditional large-scale population surveillance and provide early-warning signals in the early stage of the outbreak of COVID-19, people in Chongqing had carried out severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) monitoring since 2023.Methods:After COVID-19 was managed with measures against Class B infectious diseases, we selected five sewage treatment plants with automatic sample collection facilities in four districts of the main city. Two samples of sewage from each sewage treatment plant were collected every week. Then SARS-CoV-2 from these samples was concentrated by aluminum hydroxide adsorption-precipitation, detected and analyzed by multiple real-time fluorescent RT-PCR.Results:From January 16 to December 31 of 2023, a total of 496 sewage samples were monitored, of which 285 samples were positive by SARS-CoV-2 nucleic acid assay, with a total detection rate of 57.46%. The detection rate of SARS-CoV-2 in weeks 3-5, 18-21 and 40-47 was 100.00%. The daily mean nucleic acid concentration of SARS-CoV-2 in sewage peaked in the 18th week, and then began to decline, entering a low level and fluctuated in epidemic period. The variable trend of daily mean concentration of SARS-CoV-2 nucleic acid was basically consistent with daily number of SARS-CoV-2 infected patients or SARS-CoV-2 positive rate in fever clinic counted by infectious disease monitoring system.Conclusions:The detection rate of SARS-CoV-2 in sewage of Chongqing is relatively high, especially in April to May, and sewage monitoring can indirectly reflect the status of COVID-19 infection.
10.Modification with IL-21 and CCL19 enhances killing efficiency and tumor infiltration of NKP30 CAR-T cells in lung cancer
Zhifeng ZHOU ; Shuoyan LIU ; Jieyu LI ; Mingqiu CHEN ; Hui LIN ; Yujie CHEN ; Weijie CHEN ; Junpeng LIN ; Hang ZHOU ; Qinfeng ZHENG
Journal of Southern Medical University 2024;44(10):1926-1936
Objective To investigate whether modification with IL-21 and CCL19 enhances killing and tumor-infiltrating efficiency of NKP30 CAR-T cells in lung cancer.Methods The modified IL-21-CCL19 NKP30 CAR-T cells expressing IL-21 and CCL19 fusion gene was constructed based on NKP30 CAR-T cells and stimulated with CD3CD28 antibodies and IL-2.The immunophenotype and migration of the cells in the presence of IL-21 were investigated using flow cytometry and migration experiments.Lactate dehydrogenase(LDH)release and sphere formation assays were used to assess the killing and infiltration capabilities of CAR-T cells,and the secretion levels of IFN-γ,IL-21 and CCL19 were determined with enzyme-linked immunospot assay(ELISPOT)and ELISA.A zebrafish model bearing HCG-27 cell xenograft was established by microinjection of the tumor cells into the yolk sac followed 24 h later by injection of the immune cells at the same site,and the fluorescence signals were captured using a fluorescent microscopy.Results The NKP30 ligand B7H6,which was almost undetectable in normal tissues and blood cells,was highly expressed(over 90%)in lung cancer cells.Compared with NKP30 CAR-T cells and conventional T cells,IL-21-CCL19 NKP30 CAR-T cells exhibited stronger proliferative and migration capabilities with the formation of central memory T cells.The reduced expressions of CTLA4 and PD1 in the constructed cells resulted in enhanced killing efficiency against lung cancer cells accompanied by significantly increased production of IFN-γ,IL-21 and CCL19.In the zebrafish models,CAR-T cells exhibited stronger cytotoxicity and proliferative abilities than typical T cells,but these differences were not statistically significant between the two CAR-T cells.Conclusion Modification of NKP30 CAR-T cells with IL-21 and CCL19 facilitates their access into solid tumors for more effective tumor cell killing while producing a large number of memory T cells.


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