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.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.
3.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.
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
;
Carcinoma, Squamous Cell/metabolism*
;
Cell Proliferation
;
DNA, Mitochondrial
;
Energy Metabolism
;
Glucose
;
Mouth Neoplasms/metabolism*
;
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism*
;
Phosphatidylinositol 3-Kinases
;
Reactive Oxygen Species
5.Medication rule and mechanism of traditional Chinese medicine in treating metabolism-associated fatty liver disease based on bioinformatics technology
ZHANG Yunkun ; YAO Rong ; LI Lin ; LI Wenli ; LI Changqing ; PAN Yu ; LI Shunxiang
Digital Chinese Medicine 2023;6(3):257-271
[Objective[ To analyze the main syndrome types, medication rules, and core prescription
characteristics of traditional Chinese medicine (TCM) in the treatment of metabolism-associated fatty liver disease (MAFLD), and to predict the anti-MAFLD mechanism of core formula, so as to provide references for the clinical application of TCM and the development of new drugs.
[Methods] Literature research on TCM in treating MAFLD was retrieved from China National
Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP),
and Wanfang Database since the establishment of the database to July 2022. Excel 2019 and
Chinese Medicine Inheritance Computing Platform (V3.0) were used for frequency analysis,
association rule analysis, and cluster analysis of effective prescriptions. The key components,
targets, and action pathways of anti-MAFLD core formulas were predicted by network pharmacology. Finally, the interactions between the obtained core components and their core targets were verified reversely by molecular docking technology.
[Results] A total of 218 articles were screened and selected, including 352 prescriptions, involving 270 traditional Chinese herbs. The drugs were used a total of 3 901 times, and a total of 10 915 cases were collected, among which the prevalence rate was higher in males. The main types of TCM syndrome included intermingled phlegm and blood stasis syndrome, liver depression and spleen deficiency syndrome, and damp-heat in liver and gallbladder syndrome, among which Shanzha (Crataegi Fructus), Danshen (Salviae Miltiorrhizae Radix et Rhizoma), Fuling (Poria), Zexie (Alismatis Rhizoma), Chaihu (Bupleuri Radix), and Baizhu (Atractylodis Macrocephalae Rhizoma) were the most frequently used. The properties of Chinese medicine primarily encompassed thermal characteristics, with a predominant emphasis on cold and warm; the flavors of herbs were predominantly characterized by bitterness and sweetness, while the majority exhibited tropism towards the spleen and liver meridians. The drugs were primarily classified based on their efficacy in tonifying deficiencies, promoting diuresis and moistening, enhancing blood circulation and removing blood stasisheat-clearing, etc. The association rules were employed to derive a set of 20 core drug pairs,
while cluster analysis was utilized to identify three distinct groups of core drug combinations.
Network pharmacological showed that the main components of the core formula “Shanzha
(Crataegi Fructus) - Danshen (Salviae Miltiorrhizae Radix et Rhizoma) - Zexie (Alismatis Rhizoma) - Chaihu (Bupleuri Radix) - Fuling (Poria)” in the treatment of MAFLD were quercetin, apigenin, puerarin, luteolin, ursolic acid, kaempferol, tanshinone IIA, emodin, paeonol, etc., which involved RAC-alpha serine/threonine-protein kinase 1 (AKT1), cellular tumor antigen p53 (TP53), interleukin (IL)-6, IL-1β, signal transducer and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR), peroxisome proliferative activated receptor gamma (PPARG), and other key targets. The molecular docking results showed that the core components had good binding to lipid and atherosclerosis, and phosphatidylinositol 3 kinase (PI3K)/AKT signaling pathway-associated proteins.
[Conclusion] The main principles of TCM for the treatment of MAFLD involve soothing the liver and strengthening the spleen, eliminating phlegm and dampness, clearing heat and dampness, as well as promoting blood circulation and removing blood stasis. The core formula may exert anti-MAFLD effects mediated through multiple components, targets, and signaling pathways. This study establishes a theoretical foundation for the clinical application of TCM in the treatment of MAFLD, and serves as a reference for further exploration of new drugs against MAFLD.
6.Surgical management of Dandy-Walker syndrome in infants and the literature review
Xiaoqiang WANG ; Jiru LI ; Yunkun WANG ; Hao XIA ; Lili XING ; Weiping WANG
Clinical Medicine of China 2023;39(2):118-121
Dandy-Walker syndrome is one of the posterior fossa malformations, which is easily confused with arachnoid cyst or cerebellar dysplasia in clinical practice, leading to misdiagnosis. Dandy-Walker syndrome is easy to be combined with hydrocephalus, resulting in increased intracranial pressure, increased head circumference, growth retardation, spastic hemiplegia and other manifestations, and can also be accompanied by other nervous system malformations. On February 27, 2021, a child with Dandy-Walker syndrome with growth retardation as the primary manifestation was admitted to Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine. After multiple surgical treatment, the child's hydrocephalus was significantly improved. Through the analysis of the clinical data of the child's operation and the treatment of complications, it is helpful to improve the clinicians' understanding of the surgical treatment of the disease.
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.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.
9.The effect of anxiety on attentional orienting of heroin addicts
Jingyi WANG ; Jingwei BIAN ; Lixia SHENG ; Yunxia JIA ; Yunkun MO ; Junfa LI ; Yanlin LUO
Chinese Journal of Nervous and Mental Diseases 2016;42(10):586-590
Objective To investigate the effect of state anxiety and trait anxiety on attentional orienting of heroin addicts. Methods State anxiety and trait anxiety was measured by State-Trait Anxiety Inventory (STAI). Forty heroin ad?dicts (36 males and 4 females) and 40 healthy controls (36 males and 4 females) participated in cue-target task. Atten?tional orienting and reorienting were measured in valid cue trials and invalid cue trails. Results Heroin addicts had sig?nificantly greater state anxiety [(42.65 ± 6.58) vs. (36.60 ± 8.91)] and trait anxiety [(44.43 ± 7.67) vs. (37.00 ± 8.63)] values than controls (P<0.05). The state anxiety was significantly correlated with orientation RT difference (r=-0.259, P=0.020) and disengaging/reorientation RT difference (r=0.333, P=0.003) in heroin addicts. Trait anxiety was also significantly cor?related with orientation RT difference (r=-0.248, P=0.026) and disengaging/reorientation RT difference (r=0.356, P=0.001) in heroin addicts. Conclusion Heroin addicts have significantly greater anxiety than healthy controls. Both their state anxiety and trait anxiety are associated with attentional orienting and disengaging/reorienting.
10.Study on numerical distance effect in amblyopic children aged from 6 to 13
Min CUI ; Na AN ; Tao FU ; Qing SU ; Yunkun MO ; Junfa LI
Chinese Journal of Behavioral Medicine and Brain Science 2016;25(12):1133-1137
Objective To investigate numerical distance effect of numerical processing in amblyopic children aged from 6 to 13. Methods 46 amblyopic children and 43 control children with normal sight were divided into 3 groups respectively:7Y group (6~8 years old),9Y group (9~10 years old) and 12Y group (11~13 years old). The numerical comparison task (judging the magnitude of number) was used in this study and error rate( ER) and reaction times ( RTs) were recorded. Results ( 1) RTs of judging the num-ber 4 (7Y group (995±100)ms,9Y group (964±141)ms,12Y group (701±125)ms) were significant lon-ger(P<0.05) than RTs of judging the number 1((882±140)ms,(790±119)ms,(550±41)ms) in 3 control groups;RTs of judging the number 6((968±116)ms,(918±126)ms,(712±125)ms) were significant lon-ger(P<0.05) than RTs of judging the number 9((862±121)ms,(774±151)ms,(625±141)ms). (2) In the 12Y group of amblyopic children:RTs of judging the number 4((942±107)ms) were significant longer (P<0.05) than RTs for judging the number 1((847±136)ms). (3) No developmental significant difference was found neither within the control children nor within amblyopic children using the RTs D-values which gained by the RTs of far distant numbers ( 1/2/8/9 ) minus close distant numbers ( 3/4/6/7 ) . Conclu-sion Only 12Y group of amblyopic children show numerical distance effect in subitizing(>5).The develop-ment of numerical processing in amblyopic children is slower than that in children with normal sight.

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