1.Role of prohibitin 2 in mitophagy pathway against atherosclerosis in rats undergoing endurance training
Mingxiao SONG ; Junshunzi CHEN ; Ningwei WANG ; Huan CAI ; Hong FENG
Chinese Journal of Tissue Engineering Research 2025;29(11):2294-2300
BACKGROUND:Exercises can reduce blood lipids and slow down the development of atherosclerosis.Atherosclerosis begins with mitochondrial dysfunction,and prohibitin 2 is involved in mitophagy by endurance training. OBJECTIVE:To explore the role of endurance training in the intervention of prohibitin 2 protein in the mitophagy autophagy pathway in atherosclerosis. METHODS:A total of 40 Wistar rats were randomly divided into control group,exercise group,atherosclerosis group and atherosclerosis combined with exercise group,with 10 rats in each group.A rat model of atherosclerosis was constructed by combining a high-fat diet(9 weeks)with vitamin D injections(weeks 1,3,and 6)in the latter two groups,while the two exercise groups were subjected to progressing intensity endurance training for 9 weeks.After the intervention,lipid and pathological detections were conducted to observe the modeling and interventional effects.Mitochondrial membrane potential and mitophagy proteins were detected by microplate reader and western blot.Immunofluorescence staining was used to observe the co-localization of mitophagy proteins in aortic tissue. RESULTS AND CONCLUSION:Lipid and pathological sections showed that compared with the atherosclerosis group,the serum low-density lipoprotein cholesterol and total cholesterol levels and aortic lipid deposition area were significantly reduced in the atherosclerosis combined with exercise group(P<0.001).The results of mitochondrial membrane potential showed that the significant decrease in mitochondrial membrane potential of the aorta in the atherosclerosis combined with exercise group was reversed(P<0.01).The results of western blot assay showed that compared with the control group,the mitochondrial protein expression of prohibitin 2,LC3Ⅱ/Ⅰ,PINK1 and Parkin was significantly increased(P<0.05),and the protein expression of PARL and PGAM5 decreased(P<0.05).Compared with the atherosclerosis group,the protein expression of PINK1 and Parkin in the mitchondria of rats in the atherosclerosis combined with exercise group was significantly decreased(P<0.05),and the protein expressions of prohibitin 2,LC3Ⅱ/Ⅰ,PARL and PGAM5 were significantly increased(P<0.05).Immunofluorescence results showed that compared with the control group,the co-localization of LC3 and PINK1 with TOMM20 was significantly increased in the atherosclerosis group(P<0.05),while compared with the atherosclerosis group,the co-localization of LC3 and PINK1 with TOMM20 was significantly increased in the atherosclerosis combined with exercise group(P<0.05).Co-localization of LC3 and PARL with prohibitin 2 was significantly increased in the atherosclerosis group compared with the control group(P<0.01),co-localization of LC3 with prohibitin 2 was significantly increased in the atherosclerosis combined with exercise group compared with the atherosclerosis group(P<0.01),and co-localization of PARL protein with prohibitin 2 was significantly decreased in the atherosclerosis combined with exercise group compared with the atherosclerosis group(P<0.01).To conclude,endurance training can induce the expression of prohibitin 2 in the inner mitochondrial membrane and promote the binding of prohibitin 2 to the mitophagy junction protein to complete mitophagy,restore mitochondrial function,and slow down the occurrence of atherosclerosis.
2.Research progress in technologies for on-site monitoring and evaluation of fatigue during military operations
Mingxiao SONG ; Lijun FAN ; Xuewei CHEN ; Libin MA ; Jiangbei CAO ; Jing WANG
Military Medical Sciences 2024;48(2):143-147
The accumulation of fatigue during military operations may lead to decreased operational efficiency and non-combat attrition,which can impact combat effectiveness.On-site monitoring and evaluation of fatigue during military operations,as an important means to keep track of military operations and bring about quick changes in training,underlie the combat effectiveness of military personnel.Focusing on the on-site monitoring and evaluation methods of fatigue during military operations,this paper reviews the determinants of such fatigue as well as on-site monitoring and comprehensive evaluation methods so as to provide reference for accurate and efficient evaluation of fatigue during military operations and for early warning of such fatigue.
3.Predictive value of triglyceride-glucose index and its derivatives for lean metabolic associated fatty liver disease
Xu DONG ; Yu GE ; Chaoqun WANG ; Mingxiao XU ; Yi CHEN ; Lin CHEN
Academic Journal of Naval Medical University 2024;45(8):973-980
Objective To explore the correlations between triglyceride glucose index(TyG)and its derivatives TyG-body mass index(BMI)and TyG-alanine transaminase(ALT)with the risk of lean metabolic associated fatty liver disease(MAFLD).Methods A total of 207 patients diagnosed with lean MAFLD and 100 lean healthy controls who received annual health examination in Health Management Center of our hospital from Jul.to Dec.2023 were enrolled.Plasma lipids,blood glucose,liver function,TyG,TyG-BMI and TyG-ALT were compared between the 2 groups.The influencing factors of lean MAFLD were analyzed by univariate and multivariate logistic regression models.All subjects were divided into 4 subgroups(Q1-Q4)according to the quartile of TyG and its derivatives,and the prevalence of lean MAFLD in each subgroup was observed.The receiver operating characteristic(ROC)curves of TyG,TyG-BMI and TyG-ALT for lean MAFLD were plotted to evaluate the prediction efficiency.Results Of the 8 764 health examination cases included,2 350(26.8%)had MAFLD,of which 207 were lean MAFLD(8.8%,207/2 350).Compared with the lean healthy controls,the patients in the lean MAFLD group were older,with more male and high BMI,and their fasting blood glucose,total cholesterol,triglyceride,low density lipoprotein-cholesterol,ALT,aspartate transaminase,γ-glutamyl transpeptidase,alkaline phosphatase,total bilirubin,TyG,TyG-BMI and TyG-ALT were significantly increased,while high density lipoprotein-cholesterol was significantly decreased(all P<0.01).Logistic regression analysis showed that age,male,and elevated ALT level were independent risk factors for lean MAFLD.The prevalence of lean MAFLD in the Q4 subgroup of TyG was significantly higher than that in the Q1 and Q2 subgroups(34.3%[71/207]vs 10.6%[22/207]and 24.2%[50/207],both P<0.05).The prevalence rates of lean MAFLD in the Q4 subgroup of TyG-BMI and the Q4 subgroup of TyG-ALT were significantly higher than those in the corresponding Q1,Q2,and Q3 subgroups(35.3%[73/207]vs 8.2%[17/207],24.6%[51/207],and 31.9%[66/207];33.8%[70/207]vs 14.0%[29/207],23.2%[48/207],and 29.0%[60/207];all P<0.05).The area under curve(AUC)of TyG-BMI in predicting lean MAFLD was 0.869 0(95%confidence interval[CI]0.825 5-0.912 6,P<0.001),which was higher than that of TyG(AUC=0.818 8[95%CI 0.768 0-0.869 6,P<0.001])and TyG-ALT(AUC=0.772 5[95%CI 0.718 7-0.826 2,P<0.001]).Conclusion TyG,TyG-BMI,and TyG-ALT are associated with lean MAFLD,and have predictive value for lean MAFLD.TyG and its derivatives are easy to calculate and cheap,and can be used for preliminary clinical assessment of lean MAFLD.
4.Efficacy and safety of neoadjuvant short-course radiotherapy combined with consolidation chemotherapy for locally advanced rectal cancer
Yifei LI ; Mingxiao CHEN ; Jia LI
Cancer Research and Clinic 2024;36(10):752-756
Objective:To investigate the short-term and long-term efficacy and adverse reactions of neoadjuvant short-course radiotherapy combined with consolidation chemotherapy for locally advanced rectal cancer.Methods:A retrospective cohort study was conducted. One hundred and fifty patients with stage Ⅱ-Ⅲ rectal cancer who underwent total rectal mesentery resection in Shanxi Province Cancer Hospital from August 2015 to August 2018 were selected and divided into the short-course radiotherapy combined with consolidation chemotherapy group (study group) and the long-course synchronous radiotherapy and chemotherapy group (control group) according to the mode of neoadjuvant radiochemotherapy, with 71 and 79 cases in each group respectively. The two groups were compared in terms of recent efficacy and occurrence of adverse reactions. Kaplan-Meier method was used for survival analysis.Results:There were no statistically significant differences in the baseline clinicopathological characteristics of patients between the two groups (all P > 0.05). The proportion of patients with descending T stage [71.8% (51/71) vs. 55.7% (44/79)], descending clinical stage [66.2% (47/71) vs. 49.4% (39/79)] and the rate of pathological complete remission [21.1% (15/71) vs. 8.9% (7/79)] in the study group were higher than those in the control group, and the differences were statistically significant (all P < 0.05). The distant metastasis-free survival (DMFS) of the study group was better than that of the control group (3-year DMFS rate: 80.3% vs. 68.4%), and the difference was statistically significant ( χ2 = 4.19, P = 0.041); the differences between the study group and the control group in terms of disease-free survival (DFS) (3-year DFS rate: 80.3% vs. 78.5%) and overall survival (OS) (5-year OS rate: 91.5% vs. 83.4%) were not statistically significant (both P > 0.05). The differences in the incidences of nausea and vomiting, diarrhoea, bone marrow suppression and malaise between the two groups were not statistically significant (all P > 0.05). Conclusions:Neoadjuvant short-course radiotherapy combined with consolidation chemotherapy for locally advanced rectal cancer is safe and effective.
5.Factors influencing the occurrence of parastomal hernia after preventive ileostomy for colorectal cancer
Yuanyuan XING ; Ying GAO ; Dongfeng CHEN ; Mingxiao GUO
Journal of Chinese Physician 2023;25(7):993-997
Objective:To explore the risk factors related to the formation of parastomal hernia (PSH) in patients with colorectal cancer after preventive ileostomy, provide Evidence-based medicine basis for prevention and treatment, and reduce the incidence of incision hernia (SSIH) at the stoma.Methods:The clinical data of 214 patients who underwent laparoscopic radical resection of colorectal cancer combined with preventive loop ileostomy in the General Surgery Department of the Linyi People′s Hospital from January 2019 to May 2021 were retrospectively analyzed. The incidence of PSH was statistically analyzed, and the risk factors of PSH were analyzed by binary logistic regression.Results:There were 177 cases of PSH in 214 patients, with an incidence rate of 82.71%. There were 5 cases of SSIH (2.34%). The results of single factor analysis showed that there were significant differences in body mass index (BMI), postoperative diversion time and the proportion of stoma through rectus abdominis muscle between the PSH group and the non PSH group (all P<0.05); The results of binary logistic regression analysis showed that BMI, postoperative diversion time, rectus abdominis muscle stoma, incision infection and liquefaction were important influencing factors for the formation of PSH after preventive loop ileostomy for colorectal cancer (all P<0.05). Conclusions:BMI, postoperative diversion time, rectus abdominis muscle stoma, incision infection and liquefaction are important influencing factors for the formation of PSH after preventive ileostomy. Intervention measures can be targeted to reduce the incidence of SSIH by reducing the risk of PSH.
6.A single-center retrospective study of percutaneous drainage clinical characteristics of grade B and C postoperative pancreatic fistula and determination of the optimal intervention time
Yunpeng GE ; Chen LI ; Yuan LIU ; Jian CHEN ; Mingxiao WU ; Jinghai SONG ; Jingyong XU
Chinese Journal of Surgery 2023;61(10):901-906
Objective:To classified the fluid location of of grade B and C postoperative pancreatic fistula (POPF) and propose processing flow.Methods:Data from 232 patients who underwent pancreatic surgery from January 2018 to December 2022 at Department of General Surgery & Hepato-billo-pancreatic,Beijing Hospital were collected retrospectively. Forty-six patients who suffered from grade B and C POPF underwent ultrasound-guided drainage. There were 32 males and 14 females, with an age of (60.2±13.7)years (range:18 to 85 years). The imaging data of postoperative CT were collected and the the fluid location was classified. Then analyzed the drainage status when patents were diagnosed as POPF. Machine learning was performed and a random forest model was applied to construct the relationship between intervention time and mortality. The optimal intervention time was calculated. The patients were then divided into early and late intervention groups and clinical data and outcomes were compared using the t test,Mann-Whitney U test, χ2 test or Fisher′s exact test between the two groups. Results:Based on the results of the random forest model, the optimal puncture time was within 5.38 days after the diagnosis of POPF. Based on the optimal time, 21 patients were subsumed into early intervention group and 25 patients were subsumed into late intervention group. The location of fluid collection was classified into four types: peripancreatic (32.7%,15/46), extra-pancreatic and epigastric (41.3%,19/46), extra-pancreatic and hypogastic (13.0%,6/46) and diffused (13.0%,6/46). The status of the drainage included normal in 10 patients (21.8%), displaced drain in 18 patients (39.1%) and drain removed or blocked in 18 patients (39.1%). The perioperative mortality rate was 19.0% (4/21) in the early intervention group and 8.0%(2/25) in the late. The late intervention group had significantly higher rates of positive drainage fluid cultures (88.0%(22/25) vs. 42.9%(10/21), χ2=10.584, P=0.001), secondary surgery (24.0%(6/25) vs. 0(0/21), P=0.025), and readmission within 90 days(32.0%(8/25) vs. 4.8%(1/21), χ2=5.381, P=0.020) than the early group, and a significantly longer postoperative hospital stay( M(IQR))(24(20)days vs. 39(53)days, Z=3.023, P=0.003). Conclusions:The location of the POPF fluid collection is classified into four types. Early radiological evaluation can detect abdominal effusion promptly,and early puncture and drainage will be beneficial in improving outcomes in these patents.
7.A single-center retrospective study of percutaneous drainage clinical characteristics of grade B and C postoperative pancreatic fistula and determination of the optimal intervention time
Yunpeng GE ; Chen LI ; Yuan LIU ; Jian CHEN ; Mingxiao WU ; Jinghai SONG ; Jingyong XU
Chinese Journal of Surgery 2023;61(10):901-906
Objective:To classified the fluid location of of grade B and C postoperative pancreatic fistula (POPF) and propose processing flow.Methods:Data from 232 patients who underwent pancreatic surgery from January 2018 to December 2022 at Department of General Surgery & Hepato-billo-pancreatic,Beijing Hospital were collected retrospectively. Forty-six patients who suffered from grade B and C POPF underwent ultrasound-guided drainage. There were 32 males and 14 females, with an age of (60.2±13.7)years (range:18 to 85 years). The imaging data of postoperative CT were collected and the the fluid location was classified. Then analyzed the drainage status when patents were diagnosed as POPF. Machine learning was performed and a random forest model was applied to construct the relationship between intervention time and mortality. The optimal intervention time was calculated. The patients were then divided into early and late intervention groups and clinical data and outcomes were compared using the t test,Mann-Whitney U test, χ2 test or Fisher′s exact test between the two groups. Results:Based on the results of the random forest model, the optimal puncture time was within 5.38 days after the diagnosis of POPF. Based on the optimal time, 21 patients were subsumed into early intervention group and 25 patients were subsumed into late intervention group. The location of fluid collection was classified into four types: peripancreatic (32.7%,15/46), extra-pancreatic and epigastric (41.3%,19/46), extra-pancreatic and hypogastic (13.0%,6/46) and diffused (13.0%,6/46). The status of the drainage included normal in 10 patients (21.8%), displaced drain in 18 patients (39.1%) and drain removed or blocked in 18 patients (39.1%). The perioperative mortality rate was 19.0% (4/21) in the early intervention group and 8.0%(2/25) in the late. The late intervention group had significantly higher rates of positive drainage fluid cultures (88.0%(22/25) vs. 42.9%(10/21), χ2=10.584, P=0.001), secondary surgery (24.0%(6/25) vs. 0(0/21), P=0.025), and readmission within 90 days(32.0%(8/25) vs. 4.8%(1/21), χ2=5.381, P=0.020) than the early group, and a significantly longer postoperative hospital stay( M(IQR))(24(20)days vs. 39(53)days, Z=3.023, P=0.003). Conclusions:The location of the POPF fluid collection is classified into four types. Early radiological evaluation can detect abdominal effusion promptly,and early puncture and drainage will be beneficial in improving outcomes in these patents.
8.Mechanism of Moringa Folium in Treatment of Constipation Based on UPLC-Q-TOF-MS and GC-MS and Network Pharmacology
Mingxiao ZHANG ; Hua LI ; Na CHEN ; Junjie XIANG ; Lujie LIN ; Zhiyong LI ; Bin YANG
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(22):182-188
Objective and MethodChemical components in four varieties of Moringa Folium (MF); traditional Indian YD, modified species of Indian species PKM1, modified species of PKM1 species PKM2, and red river No.1 variety HH) were qualitatively analyzed by ultra-high performance liquid chromatography quadrupole time of flight mass spectrometry(UPLC-Q-TOF-MS) and gas chromatography mass spectrometry(GC-MS), and potential mechanism and material basis of MF in the treatment of constipation were revealed based on network pharmacology. ResultData of accurate relative molecular mass and fragment ions in primary and secondary mass spectra in both positive and negative ion modes were acquired by UPLC-Q-TOF-MS, and then 20 nonvolatile components were identified from the four varieties by comparison with references and consulting literature reports. Nineteen volatile components were identified by comparing mass spectrometry information and that in NIST (version 1.7) based on GC-MS, and 674 chemical component targets were predicted using SwissTargetPrediction and SEA after integration and duplicate elimination. A total of 1 086 constipation-related targets were predicted using GeneCards. With Venny, 88 intersection targets were obtained by mapping chemical component targets and disease targets and venny diagram was drawn. STRING and Cytoscape were used to plot protein-protein interaction(PPI) network diagram. Gene ontology(GO) function analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway analysis were completed through Metascape, which indicated that MF treated constipation mainly via thyroid hormone signaling pathway, advanced glycation end products/receptor for advanced glycation end products(AGE/RAGE) signaling pathway, and cancer signaling pathway. Additionally, the "component-target-pathway" map was plotted by Cytoscape, which predicted that the key components of MF in the treatment of constipation were adenosine, astragalin, geranylacetone, 2-methyloctan-3-one, palmitic acid and oleamide. Also, we inferred that the core targets might be prostaglandin-endoperoxide synthase 2(PTGS2), tumor necrosis factor(TNF), mitogen-activated protein kinase 1(MAPK1), alpha 2A adrenergic receptor(ADRA2A), and interleukin (IL)-6, which distributed in multiple tissues such as colon, small intestine, and rectum. ConclusionThis study clarified the volatile and non-volatile divisions in four varieties of MF comprehensively, and explained that MF treated constipation by reducing inflammatory state and promoting intestinal movement and secretion of intestinal fluid, which provided reference for further quality evaluation and clinical research of MF.
9.Changes of serum progastrin-releasing peptide and neuron specific enolase levels in the concurrent chemoradiotherapy of small cell lung cancer and their significances
Zhetao MI ; Mingxiao CHEN ; Baoguo TIAN
Cancer Research and Clinic 2021;33(1):38-41
Objective:To observe the changes of serum progastrin-releasing peptide (Pro-GRP) and neuron specific enolase (NSE) levels in patients with small cell lung cancer (SCLC) in the concurrent chemoradiotherapy and their significances.Methods:The data of 80 patients with SCLC who were admitted to Shanxi Provincial Cancer Hospital from June 2018 to December 2019 were retrospectively analyzed, and the patients were divided into the concurrent chemoradiotherapy group (26 cases) and chemotherapy alone group (54 cases). Enzyme-linked immunosorbent assay (ELISA) and electrochemiluminescence method were used to detect serum Pro-GRP and NSE levels before and after treatment; and the association of Pro-GRP and NSE levels with patients' condition, treatment method, treatment stage and treatment efficacy was analyzed.Results:Among 80 patients with SCLC, Pro-GRP level of patients with limited-stage [127.43 pg/ml (17.61- 1 547.30 pg/ml)] was lower than that of patients with extensive-stage [547.87 pg/ml (20.20-2 111.00 pg/ml)], and the difference was statistically significant ( U = 312.65, P < 0.01). NSE level of patients with limited-stage [25.02 μg/L (4.72-64.64 μg/L)] was also lower than that of patients with extensive-stage [88.08 μg/L (5.52-104.64 μg/L)], and the difference was statistically significant ( U = 203.14, P < 0.01). The levels of Pro-GRP and NSE in the concurrent chemoradiotherapy group and the chemotherapy alone group were decreased after 2 and 4 cycles of chemotherapy compared with those before treatment, and the differences were statistically significant (all P < 0.01); the decrease range in the concurrent chemoradiotherapy group was more than that in the chemotherapy alone group, but the differences between the two groups were not statistically significant (all P > 0.05). The objective response rate in the concurrent chemoradiotherapy group was 96.15% (25/26), which was higher than that in the chemotherapy alone group [70.37% (38/54)], and the difference was statistically significant ( χ2 = 6.972, P = 0.008). Conclusions:The serum levels of Pro-GRP and NSE for patients with SCLC in the concurrent chemoradiotherapy can reflect the changes of the condition of SCLC patients. Concurrent chemoradiotherapy is more effective compared with the chemotherapy alone in the treatment of SCLC.
10.Comparison of single infusion of anti-BCMA versus combined infusion of anti-CD19 chimeric antigen receptor T cells for immune reconstruction in relapsed/refractory multiple myeloma
Jiao GE ; Tingting ZHAO ; Chongyang WAN ; Jieyun XIA ; Siyi GUO ; Mingxiao YU ; Juan CHEN ; Ying WANG ; Kailin XU ; Zhenyu LI
Chinese Journal of Hematology 2021;42(9):733-738
Objective:We observed and compared the differences in immune reconstruction between single-infusion anti-B-cell maturation antigen (BCMA) , chimeric antigen receptor T cells (CAR-T) , and combined infusion of anti-CD19 CAR-T cells in the treatment of recurrent/refractory multiple myeloma (RRMM) .Methods:Sixty-one patients with RRMM who underwent CAR-T cell therapy in our hospital from June 2017 to December 2020 were selected. Among them, 26 patients received anti-BCMA target, and 35 patients received anti-BCMA combined with anti-CD19 target. Using flow cytometry, we determined T cell subsets (CD3 +, CD4 +, CD8 +, CD4 +/CD8 +) , B cells (CD19 +) , and NK cells (CD16 + CD56 +) at different time points before and after CAR-T treatment, and detected immunoglobulin IgG, IgA and IgM levels by immunoturbidimetry. We compared the reconstruction rules of lymphocyte subsets and immunoglobulins in the two groups. Results:CD8 + T lymphocytes recovered most rapidly after the infusion of CAR-T cells, returning to pre-infusion levels at 3 months and 1 month after infusion, respectively[BCMA: 695 (357, 1264) /μl vs 424 (280, 646) /μl; BCMA+CD19: 546 (279, 1672) /μl vs 314 (214, 466) /μl]. NK cells returned to normal levels at 3 months after infusion in both groups[BCMA: 171 (120, 244) /μl, BCMA+CD19: 153 (101, 218) /μl (Normal reference range 150-1100/μl) ]; however, the NK cells were not maintained at stable levels in the BCMA CAR-T cells group. The recovery of CD4 + T lymphocytes in both groups was slow and remained persistently low within 12 months after infusion, and no recovery was observed in most patients. The reversal of the ratio of CD4 +/CD8 + lasted for more than a year. The levels of CD19 + B cells in both groups returned to baseline 3 months after infusion[BCMA: 62 (10, 72) /μl vs 57 (24, 78) /μl; BCMA+CD19: 40 (4, 94) /μl vs 29 (14, 46) /μl]. IgG returned to the pre-infusion level 12 months after infusion in the group with anti-BCMA cells alone, but not in the group with combined infusion of CD19 CAR T cells[7.82 (6.03, 9.64) g/L vs 6.92 (4.62, 12.76) g/L]. IgA returned to pre-infusion levels at 9 and 12 months after infusion, respectively[BCMA: 0.46 (0.07, 0.51) g/L vs 0.22 (0.12, 4.01) g/L; BCMA+CD19: 0.46 (0.22, 0.98) g/L vs 0.27 (0.10, 0.53) g/L]. IgM in both groups returned to pre-infusion levels 6 months after infusion[BCMA: 0.43 (0.06, 0.60) g/L vs 0.20 (0.13, 0.37) g/L; BCMA+CD19: 0.53 (0.10, 0.80) g/L vs 0.16 (0.11, 0.28) g/L]. There was no significant difference in the indexes of lymphocyte subpopulation reconstruction and immunoglobulin recovery between the two groups at each time point. Conclusion:This study showed that in patients with RRMM treated with CAR-T cells, the appropriate target antigen can be selected without considering the difference of immune reconstruction between anti-BCMA CAR-T and combined anti-CD19 CAR-T therapy.

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