1.Prodrug-based combinational nanomedicine remodels lipid metabolism for reinforced ferroptosis and immune activation.
Ling LIN ; Zaixiang FANG ; Guohao LIU ; Yiwei LIU ; Zhiqian LI ; Dayi PAN ; Yunkun LI ; Hemi KANG ; Xiaoding SHEN ; Jingyao ZHANG ; Qiyong GONG ; Kui LUO ; Jing JING
Acta Pharmaceutica Sinica B 2025;15(5):2746-2763
Ferroptosis is a form of programmed cell death characterized by overwhelmed lipid oxidation, and it has emerged as a promising strategy for cancer therapy. Enhanced ferroptosis could overcome the limitations of conventional therapeutic modalities, particularly in difficult-to-treat tumors. In this study, we developed a dual-modality therapy in nanomedicine by combining paclitaxel (PTX) chemotherapy and pyropheophorbide-a (Ppa) phototherapy. Heparin (HP) was grafted with poly(N-(2'-hydroxy) propyl methacrylamide) (pHPMA) using reversible addition-fragmentation chain transfer polymerization to form HP-pHPMA (HH), which was utilized to deliver Ppa and PTX, yielding HP-pHPMA-Ppa (HH-Ppa) and HP-pHPMA-PTX (HH-PTX), respectively. The prodrug-based combinational nanomedicine (HH-PP) was formed by co-assembly of HH-PTX and HH-Ppa. It was found that HH-PP treatment significantly disrupted lipid metabolism in triple-negative breast cancer (TNBC) cells, induced extensive lipid oxidation, and promoted ferroptosis. In vivo, HH-PP intervention achieved a tumor growth inhibition rate of 86.63% and activated adaptive immunity with an elevated CD8+ cytotoxic T cell infiltration level. This combinational nanomedicine offers a promising platform for co-delivery of multiple therapeutic agents. It exerts a promising anti-tumor effect via enhanced ferroptosis and ferroptosis-induced immune activation by disrupting lipid metabolism in TNBC cancer cells.
2.Case of tooth autotransplantation with robotic surgery assistance.
Yunkun LIU ; Jia SONG ; Xiaoyu CHEN ; Chuyang ZHANG ; Shang CHEN ; Jian ZHANG ; Zhiyu GU
West China Journal of Stomatology 2025;43(6):881-887
Tooth autotransplantation is a restoration technology that grafts the patient's own teeth to the missing tooth area, usually by using the third molar to replace a nonnormally functioning molar for the purpose of "turning waste into treasure". Robotic surgical assistance has been widely used in the fields of breast cancer, liver cancer, and orthopedics; however, its application in the dental field, particularly in tooth autotransplantation, remains relatively rare. This paper reports a case of tooth autotransplantation with the assistance of a domestic autonomous oral surgery robot, providing a reference for the application of robotic surgery assistance in tooth autotransplantation.
Humans
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Molar, Third/transplantation*
;
Robotic Surgical Procedures/methods*
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Transplantation, Autologous
3.Clinical Study on Feisu Granules for the Treatment of Acute Exacerbation of COPD with Syndrome of Phlegm-heat and Blood Stasis of Lung
Yunkun CHEN ; Qin LI ; Enyao WEI ; Feng ZHANG ; Jie WANG ; Xiuhua LI ; Huang LIU
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(4):170-174
Objective To observe the clinical efficacy of Feisu Granules,and its effects on quality of life,coagulation and immune function in acute exacerbation of chronic obstructive pulmonary disease(AECOPD)with syndrome of phlegm-heat and blood stasis of lung.Methods Totally 120 AECOPD patients were divided into observation group and control group according to random number table method,with 60 cases in each group.The control group was given conventional Western medicine treatment,and the observation group received Feisu Granules treatment on the basis of the control group,one bag each time,three times a day,orally.The treatment for both groups lasted for 7 d.The clinical efficacy of both groups were observed.TCM symptom scores,St.George's respiratory questionnaire(SGRQ)score,coagulation function indexes(fibrinogen,D-dimer),and immune function indexes(CD4+,CD8+,CD4+/CD8+)of both groups were compared.The side effects were observed.Results The total effective rate in the observation group(93.10%)was significantly higher than that of the control group(79.66%),with statistical significance(P<0.05).Compared with before treatment,TCM symptom scores,scores of cough,wheezing,venous congestion,and SGRQ score decreased in both groups after treatment(P<0.05);after treatment,the observation group had lower above scores than the control group(P<0.05).Compared with before treatment,both groups showed a decrease in plasma fibrinogen and D-dimer levels after treatment(P<0.05);after treatment,the observation group showed lower levels of plasma fibrinogen and D-dimer compared with the control group(P<0.05).Compared with before treatment,the peripheral blood CD4+ and CD4+/CD8+ levels in both groups significantly increased after treatment,while CD8+ levels significantly decreased(P<0.05);after treatment,the peripheral blood CD4+ and CD4+/CD8+ in the observation group were higher than those in the control group,while CD8+ was lower than those in the control group(P<0.05).Neither group had any drug-related side effects.Conclusion On the basis of conventional Western medicine,the combination of Feisu Granules in the treatment of AECOPD with syndrome of phlegm-heat and blood stasis of lung can significantly improve clinical efficacy,improve patient quality of life,facilitate coagulation function recovery,and enhance cellular immune function.
4.Knockdown of PGC1α suppresses dysplastic oral keratinocytes proliferation through reprogramming energy metabolism.
Yunkun LIU ; Nengwen HUANG ; Xianghe QIAO ; Zhiyu GU ; Yongzhi WU ; Jinjin LI ; Chengzhou WU ; Bo LI ; Longjiang LI
International Journal of Oral Science 2023;15(1):37-37
Oral potentially malignant disorders (OPMDs) are precursors of oral squamous cell carcinoma (OSCC). Deregulated cellular energy metabolism is a critical hallmark of cancer cells. Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC1α) plays vital role in mitochondrial energy metabolism. However, the molecular mechanism of PGC1α on OPMDs progression is less unclear. Therefore, we investigated the effects of knockdown PGC1α on human dysplastic oral keratinocytes (DOKs) comprehensively, including cell proliferation, cell cycle, apoptosis, xenograft tumor, mitochondrial DNA (mtDNA), mitochondrial electron transport chain complexes (ETC), reactive oxygen species (ROS), oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and glucose uptake. We found that knockdown PGC1α significantly inhibited the proliferation of DOKs in vitro and tumor growth in vivo, induced S-phase arrest, and suppressed PI3K/Akt signaling pathway without affecting cell apoptosis. Mechanistically, downregulated of PGC1α decreased mtDNA, ETC, and OCR, while enhancing ROS, glucose uptake, ECAR, and glycolysis by regulating lactate dehydrogenase A (LDHA). Moreover, SR18292 (an inhibitor of PGC1α) induced oxidative phosphorylation dysfunction of DOKs and declined DOK xenograft tumor progression. Thus, our work suggests that PGC1α plays a crucial role in cell proliferation by reprograming energy metabolism and interfering with energy metabolism, acting as a potential therapeutic target for OPMDs.
Humans
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Carcinoma, Squamous Cell/metabolism*
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Cell Proliferation
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DNA, Mitochondrial
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Energy Metabolism
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Glucose
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Mouth Neoplasms/metabolism*
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Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism*
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Phosphatidylinositol 3-Kinases
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Reactive Oxygen Species
5.Research progress on oral microbiota application in forensic medicine
Zhiyu GU ; Yunkun LIU ; Yijie CHEN ; Jiashuang LI ; Yingqian DUAN ; Xueqin SUN ; Yang LI
Chinese Journal of Forensic Medicine 2023;38(6):687-691
Forensic science is looking for clues at a crime scene in order to reconstruct the crime scene.Classic clues include DNA and fingerprints.Forensic microbiology is a branch of forensic medicine that uses microbes as clues,providing us information about lifestyle,circadian rhythms,geographic locations,postmortem intervals,cancers,and oral or systemic diseases.Oral cavity,as the place with the second largest number of microorganisms,can provide researchers with microbial information of each ecological niche,and assist in the prediction,diagnosis and monitoring of oral or systemic diseases.This paper reviews the composition of oral microbiome,the application in oral diseases,systemic diseases and forensic medicine,with the aim of providing some references for the development of forensic microbiology based on oral microbiome.
6.Analysis of short-term efficacy of perioperative fecal microbiota transplantation combined with nutritional support in patients with radiation-induced enteritis complicated by intestinal obstruction
Jiaqu CUI ; Hongliang TIAN ; Xujie WANG ; Le WANG ; Yunkun LIU ; Chen YE ; Liangfu DING ; Ning LI ; Qiyi CHEN
Chinese Journal of Gastrointestinal Surgery 2023;26(10):955-962
Objective:To explore the short-term efficacy of perioperative fecal microbiota transplantation combined with nutritional support in patients with radiation-induced enteritis complicated by intestinal obstruction.Methods:The cohort of this prospective cohort study comprised 45 patients (nine men and 36 women) with radiation-induced enteritis complicated by intestinal obstruction admitted to Shanghai Tenth People's Hospital Affiliated to Tongji University from January 2022 to October 2022. The median age was 53 (42–65) years. Thirty-five of the patients had gynecological tumors and 10 colorectal malignancies. The patients were randomly allocated to a fecal microbiota transplantation group of 20 patients who underwent fecal microbiota transplantation starting 2 weeks before surgery for 6 days, in addition to receiving conventional perioperative treatment, and a conventional treatment group of 25 patients who only received nutritional support during the perioperative period. There were no significant differences in baseline characteristics (sex, age, preoperative nutritional indices, and surgical procedure) between the two groups (all P>0.05). Postoperative recovery (time to passing flatus or a bowel movement, length of stay) and complications were compared between the two groups. Postoperative complications within 30 days after surgery classified in accordance with the international Clavien–Dindo classification of surgical complications (I–V) were statistically analyzed. Improvement in gastrointestinal symptoms, namely abdominal pain, distension, diarrhea, and rectal bleeding) and gastrointestinal quality of life scores (which include 36 problems rated 0–144 points related to physical, psychological, social activities and family life; the lower the score, the more severe the symptoms) were compared between the two groups. Nutritional recovery was assessed by body mass, body mass index, total protein, albumin, prealbumin, and hemoglobin. Results:Compared with the conventional treatment group, the postoperative hospital stay was shorter in the fecal microbiota transplantation group (8.0±4.3 days vs. 11.2±5.4 days, t=2.157, P=0.037) and the time to passage of flatus or having a bowel movement was earlier (2.2±3.2 days vs. 3.9±2.3 days, t=2.072, P=0.044). There were 26 postoperative complications in the fecal microbiota transplantation group and 59 in the conventional treatment group. There were 20 and 36 Grade I to II complications and no and three Grade III to V complications in the transplantation and conventional treatment group, respectively. The overall grade of complication did not differ significantly between the two groups ( P=0.544). However, the incidence of postoperative intestinal inflammatory obstruction was lower in the fecal microbiota transplantation than the conventional treatment group (10.0% [2/20] vs. 40.0% [10/25], P=0.040). One patient in the conventional treatment group died. This patient had complete intestinal obstruction complicated by severe malnutrition preoperatively, and an intestinal fistula complicated by abdominal infection postoperatively, and died despite active treatment. Nineteen and 23 patients in the transplantation and conventional treatment group, respectively, attended for follow-up 1 month after surgery; 19 and 21, respectively, attended for follow-up 3 months after surgery, and 17 and 20, respectively, attended for follow-up 6 months after surgery. There were no significant differences between the two groups in abdominal pain or rectal bleeding 1, 3, or 6 months after surgery (all P>0.05). One month after surgery, the incidence of abdominal distension and diarrhea was lower in the fecal microbiota transplantation than in the conventional treatment group (3/19 vs. 48.0% [11/23], P=0.048; 3/19 vs. 52.2% [12/23], P=0.023). However, at the 3 and 6 month follow-ups the incidence of abdominal distension and diarrhea had gradually decreased in both groups and the differences between the groups were not statistically significant ( P>0.05 for all). Scores for gastrointestinal quality of life improved significantly in both treatment groups compared with preoperative values ( F=71.250, P<0.001; F=79.130, P<0.001, respectively). Scores for gastrointestinal quality of life were higher in the fecal microbiota transplantation than the conventional treatment group at all follow-up time points ( P<0.05). One-way ANOVA showed that body mass, body mass index, and total protein, albumin and hemoglobin concentrations improved in both groups compared with preoperative values (all P<0.05). Prealbumin concentration improved significantly in the transplantation ( F=5.514, P=0.002), but not in the conventional, group ( F=1.535, P=0.211). The improvements in body mass, body mass index, total protein, and albumin were better in the fecal microbiota transplantation than conventional treatment group at 3 and 6 months of follow-up (all P<0.05). Conclusion:Perioperative fecal microbiota transplantation combined with nutritional support is effective in improving early postoperative nutritional status and quality of life in patients with radiation-induced enteritis complicated by intestinal obstruction.
7.Analysis of short-term efficacy of perioperative fecal microbiota transplantation combined with nutritional support in patients with radiation-induced enteritis complicated by intestinal obstruction
Jiaqu CUI ; Hongliang TIAN ; Xujie WANG ; Le WANG ; Yunkun LIU ; Chen YE ; Liangfu DING ; Ning LI ; Qiyi CHEN
Chinese Journal of Gastrointestinal Surgery 2023;26(10):955-962
Objective:To explore the short-term efficacy of perioperative fecal microbiota transplantation combined with nutritional support in patients with radiation-induced enteritis complicated by intestinal obstruction.Methods:The cohort of this prospective cohort study comprised 45 patients (nine men and 36 women) with radiation-induced enteritis complicated by intestinal obstruction admitted to Shanghai Tenth People's Hospital Affiliated to Tongji University from January 2022 to October 2022. The median age was 53 (42–65) years. Thirty-five of the patients had gynecological tumors and 10 colorectal malignancies. The patients were randomly allocated to a fecal microbiota transplantation group of 20 patients who underwent fecal microbiota transplantation starting 2 weeks before surgery for 6 days, in addition to receiving conventional perioperative treatment, and a conventional treatment group of 25 patients who only received nutritional support during the perioperative period. There were no significant differences in baseline characteristics (sex, age, preoperative nutritional indices, and surgical procedure) between the two groups (all P>0.05). Postoperative recovery (time to passing flatus or a bowel movement, length of stay) and complications were compared between the two groups. Postoperative complications within 30 days after surgery classified in accordance with the international Clavien–Dindo classification of surgical complications (I–V) were statistically analyzed. Improvement in gastrointestinal symptoms, namely abdominal pain, distension, diarrhea, and rectal bleeding) and gastrointestinal quality of life scores (which include 36 problems rated 0–144 points related to physical, psychological, social activities and family life; the lower the score, the more severe the symptoms) were compared between the two groups. Nutritional recovery was assessed by body mass, body mass index, total protein, albumin, prealbumin, and hemoglobin. Results:Compared with the conventional treatment group, the postoperative hospital stay was shorter in the fecal microbiota transplantation group (8.0±4.3 days vs. 11.2±5.4 days, t=2.157, P=0.037) and the time to passage of flatus or having a bowel movement was earlier (2.2±3.2 days vs. 3.9±2.3 days, t=2.072, P=0.044). There were 26 postoperative complications in the fecal microbiota transplantation group and 59 in the conventional treatment group. There were 20 and 36 Grade I to II complications and no and three Grade III to V complications in the transplantation and conventional treatment group, respectively. The overall grade of complication did not differ significantly between the two groups ( P=0.544). However, the incidence of postoperative intestinal inflammatory obstruction was lower in the fecal microbiota transplantation than the conventional treatment group (10.0% [2/20] vs. 40.0% [10/25], P=0.040). One patient in the conventional treatment group died. This patient had complete intestinal obstruction complicated by severe malnutrition preoperatively, and an intestinal fistula complicated by abdominal infection postoperatively, and died despite active treatment. Nineteen and 23 patients in the transplantation and conventional treatment group, respectively, attended for follow-up 1 month after surgery; 19 and 21, respectively, attended for follow-up 3 months after surgery, and 17 and 20, respectively, attended for follow-up 6 months after surgery. There were no significant differences between the two groups in abdominal pain or rectal bleeding 1, 3, or 6 months after surgery (all P>0.05). One month after surgery, the incidence of abdominal distension and diarrhea was lower in the fecal microbiota transplantation than in the conventional treatment group (3/19 vs. 48.0% [11/23], P=0.048; 3/19 vs. 52.2% [12/23], P=0.023). However, at the 3 and 6 month follow-ups the incidence of abdominal distension and diarrhea had gradually decreased in both groups and the differences between the groups were not statistically significant ( P>0.05 for all). Scores for gastrointestinal quality of life improved significantly in both treatment groups compared with preoperative values ( F=71.250, P<0.001; F=79.130, P<0.001, respectively). Scores for gastrointestinal quality of life were higher in the fecal microbiota transplantation than the conventional treatment group at all follow-up time points ( P<0.05). One-way ANOVA showed that body mass, body mass index, and total protein, albumin and hemoglobin concentrations improved in both groups compared with preoperative values (all P<0.05). Prealbumin concentration improved significantly in the transplantation ( F=5.514, P=0.002), but not in the conventional, group ( F=1.535, P=0.211). The improvements in body mass, body mass index, total protein, and albumin were better in the fecal microbiota transplantation than conventional treatment group at 3 and 6 months of follow-up (all P<0.05). Conclusion:Perioperative fecal microbiota transplantation combined with nutritional support is effective in improving early postoperative nutritional status and quality of life in patients with radiation-induced enteritis complicated by intestinal obstruction.
8.Biomechanical Study on Personalized Titanium Alloy Short Femoral Prosthesis
Hongwei LIU ; Wen ZHANG ; Junfeng JIANG ; Yiping WENG ; Nanwei XU ; Yunkun ZHANG ; Caimei WANG
Journal of Medical Biomechanics 2021;36(3):E359-E364
Objective To evaluate biomechanical properties of the personalized titanium alloy short femoral prosthesis by finite element analysis. Methods Based on the validated femoral finite element model, the base of the femoral neck was simulated, and by inserting different short femoral prostheses, four total hip replacement (THR) models, namely, the SMF stem model (Model A), BE1 stem model (Model B), MINI stem model (Model C) and personalized stem model (Model D) were established, respectively. The same loads and constraints were applied to four groups of models, and the von Mises stress distribution and deformation were calculated and analyzed, so as to compare mechanical stability of each model. Results The deformation of all THR models was smaller than that of the femur model under physiological state. The deformation of Model B was close to that of Model C, and the deformation of Model A was close to that of Model D. The peak stress of Model C was higher than that of the other 3 models, reaching 9555 MPa. The overall stress trend was Model C > Model B > Model D> Model A > Model under physiological state. Conclusions The peak stress, stress distribution of personalized short femoral stem were similar to that of SMF stem, with reasonable stress distribution, small stress shielding of the proximal femur, minimum overall deformation and shear stress of the prosthesis, and its effectiveness and stability could meet the requirements of human biomechanics, which could provide references for joint surgeons and prosthesis researchers.
9.Effect of Yang-Xue Qing-Nao Granules on Protein Expression of BDNF and bFGF in CA1 Area of Hippocampus among Vascular Dementia Rats
Jinxia ZHANG ; Yunkun SAN ; Jing LI ; Yuanyuan MA ; Bin LIU
World Science and Technology-Modernization of Traditional Chinese Medicine 2015;(11):2246-2251
This study was aimed to observe the effect of Yang-Xue Qing-Nao(YXQN) granules on the expression of brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF) in CA1area of hippocampus among vascular dementia (VD) rats.A total of 72 SD rats were randomly divided into the sham operation group,VD model group (model group) and YXQN treatment group (treatment group).The VD rat model was prepared by modified Pulsineli's four-vessel occlusion.The learning and memory abilities of rats were detected by the Morris water maze.The protein expressions of BDNF and bFGF were detected by the immunohistochemical analysis.The results showed that compared with the sham operation group,there was obvious learning and memory disorders in the model group with increased protein expressions of BDNF and bFGF in CA1 area of hippocampus at difference time points (P<0.01).Compared with the model group,the learning and memory abilities of rats in the treatment group were significantly improved; and the protein expressions of BDNF and bFGF in CA1 area of hippocampus were significantly increased at difference time points (P<0.01).The expression was the highest on the 4th week.It was concluded that YXQN granules can improve the learning and memory abilities of VD rats.Its mechanism may be related to the upregulation of protein expression of BDNF and bFGF.
10.Effect of Yangxue Qingnao Granule on Ultrastructures and Expression of p38 Mitogen Activated Protein Kinases in CA1 Area of Hippocampus of Vascular Dementia Rats
Yunkun SAN ; Jinxia ZHANG ; Bin LIU ; Ying LIU ; Shiying LI
Chinese Journal of Rehabilitation Theory and Practice 2015;(11):1245-1250
Objective To observe the effect of Yangxue Qingnao Granule on the ultrastructures and expression of p38 mitogen activated protein kinases (p38MAPK) in CA1 area of hippocampus in vascular dementia rats. Methods 180 Sprague-Dawley rats were randomly di-vided into sham group, vascular dementia model group (model group) and Yangxue Qingnao Granule treatment group (treatment group). The vascular dementia was modeled with modified Pulsineli's four-vessel occlusion. The ultrastructure of CA1 area was observed with trans-mission electron microscope, while the expression of p38MAPK in CA1 area was detected with immunohistochemstry and Western blotting 1, 2, 4 and 8 weeks after modeling. Results In the model group, pyknosis, nuclear dissolution, heterochromatin margination and mitochon-dria swelling were found in most of the neurons in CA1. In the treatment group, the distribution of chromatin was well-proportioned, and mi-tochondrion and other organelle were normal. In the model group, the expression of p38MAPK increased at each time point compared with the sham group (P<0.01), and peaked 4 weeks after modeling, and decreased in the treatment group compared with the model group (P<0.01). Conclusion Yangxue Qingnao Granule can improve the ultrastructure of neuronal in CA1 area of hippocampus of vascular dementia rats, which may relate with the inhibition of the expression of p38MAPK.


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