1.Effect of sodium-glucose cotransporter 2 inhibitor empagliflozin in alleviating uremic cardiomyopathy and related mechanism
Shi CHENG ; Yeqing XIE ; Wei LU ; Jiarui XU ; Yong YU ; Ruizhen CHEN ; Bo SHEN ; Xiaoqiang DING
Chinese Journal of Clinical Medicine 2025;32(2):248-258
		                        		
		                        			
		                        			Objective To investigate the effect of sodium-glucose cotransporter 2 inhibitor (empagliflozin, EMPA) on myocardial remodeling in a mouse uremic cardiomyopathy (UCM) model induced by 5/6 nephrectomy, through the phosphatidylinositol 3 kinase (PI3K)/protein kinase B (PKB/AKT)/p65 signaling pathway. Methods The animals were divided into three groups: Sham group (n=6), UCM group (n=8), and UCM+EMPA group (n=8). A UCM model was established in C57BL/6N mice using the 5/6 nephrectomy. Starting from 5 weeks post-surgery, EMPA or a placebo was administered. After 16 weeks, blood pressure, serum creatinine, blood urea nitrogen, 24-hour urine glucose and urine sodium were measured. Cardiac structure and function were assessed by echocardiography. Hematoxylin-eosin (HE) staining and Masson trichrome staining were used to observe pathological changes in the heart and kidneys. Wheat germ agglutinin (WGA) staining was used to evaluate myocardial hypertrophy. The real-time quantitative PCR (RT-qPCR) was used to detect the expression levels of myocardial hypertrophy- and fibrosis-related mRNAs. Western blotting was used to detect the expression levels of PI3K, AKT and p65 in myocardial tissues. Results After 16 weeks, UCM group exhibited significantly higher blood pressure, serum creatinine, blood urea nitrogen than sham group (P<0.01); UCM+EMPA group exhibited lower blood pressure, serum creatinine, blood urea nitrogen, and higher 24 h urine sodium and glucose than UCM group (P<0.05). Echocardiographic results showed ventricular remodeling in the UCM group, evidenced by left ventricular wall thickening, left ventricular enlargement, increased left ventricular mass, and decreased systolic function (P<0.05); ventricular remodeling was alleviated (P<0.05), though there was no significant improvement in systolic function in UCM+EMPA group. HE and Masson stainings revealed myocardial degeneration, necrosis, and interstitial fibrosis in UCM group (P<0.01); the myocardial pathology improved with reduced collagen deposition in UCM+EMPA group (P<0.01). WGA staining confirmed myocardial hypertrophy in UCM group (P<0.01), while myocardial hypertrophy was alleviated in UCM+EMPA group (P<0.01). RT-qPCR results showed myocardial hypertrophy- and fibrosis-related genes (NPPA, NPPB, MYH7, COL1A1, COL3A1, TGF-β1) were upregulated in UCM group (P<0.05), but downregulated in UCM+EMPA group. Western blotting showed PI3K, p-AKT/AKT ratio, and p-p65/p65 ratio were increased in UCM group, but decreased in UCM+EMPA group (P<0.05). Conclusion EMPA can improve myocardial hypertrophy and fibrosis in the UCM mouse model, and it may play the role through inhibiting the PI3K/AKT/p65 signaling pathway.
		                        		
		                        		
		                        		
		                        	
2.Integrated Transcriptomic Landscape and Deep Learning Based Survival Prediction in Uterine Sarcomas
Yaolin SONG ; Guangqi LI ; Zhenqi ZHANG ; Yinbo LIU ; Huiqing JIA ; Chao ZHANG ; Jigang WANG ; Yanjiao HU ; Fengyun HAO ; Xianglan LIU ; Yunxia XIE ; Ding MA ; Ganghua LI ; Zaixian TAI ; Xiaoming XING
Cancer Research and Treatment 2025;57(1):250-266
		                        		
		                        			 Purpose:
		                        			The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). 
		                        		
		                        			Materials and Methods:
		                        			Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. 
		                        		
		                        			Results:
		                        			A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. 
		                        		
		                        			Conclusion
		                        			USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients. 
		                        		
		                        		
		                        		
		                        	
3.Integrated Transcriptomic Landscape and Deep Learning Based Survival Prediction in Uterine Sarcomas
Yaolin SONG ; Guangqi LI ; Zhenqi ZHANG ; Yinbo LIU ; Huiqing JIA ; Chao ZHANG ; Jigang WANG ; Yanjiao HU ; Fengyun HAO ; Xianglan LIU ; Yunxia XIE ; Ding MA ; Ganghua LI ; Zaixian TAI ; Xiaoming XING
Cancer Research and Treatment 2025;57(1):250-266
		                        		
		                        			 Purpose:
		                        			The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). 
		                        		
		                        			Materials and Methods:
		                        			Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. 
		                        		
		                        			Results:
		                        			A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. 
		                        		
		                        			Conclusion
		                        			USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients. 
		                        		
		                        		
		                        		
		                        	
4.Pathogen spectrum of diarrheal disease surveillance in Fengxian District, Shanghai, 2013‒2023
Meihua LIU ; Yuan ZHUANG ; Xiaohong XIE ; Hongwei ZHAO ; Yuan SHI ; Lijuan DING ; Yi HU ; Lixin TAO
Shanghai Journal of Preventive Medicine 2025;37(4):336-341
		                        		
		                        			
		                        			ObjectiveTo investigate the pathogenic spectrum and epidemiological characteristics of diarrheal disease in Fengxian District of Shanghai, and to provide scientific basis for the prevention and control of diarrheal diseases. MethodsBasic information of the initial adult cases visited diarrheal disease surveillance sentinel hospital in Fengxian District, Shanghai, was collected from August 2013 to 2023, and fecal samples were collected at 1∶5 sampling intervals to isolate and identify 5 kinds of diarrheagenic Escherichia coli (DEC), Salmonella (SAL), Vibrio parahaemolyticus, Campylobacter, Vibrio cholerae, Shigella and Yersinia enterocolitica (YE). Simultaneously, nucleic acid detection was performed for 3 kinds of rotavirus, 2 kinds of norovirus, intestinal adenovirus, astrovirus and sapovirus. ResultsA total of 1 861 cases of newly diagnosed diarrheal disease were reported, with the peak in July to August. Additionally, 704 surveillance samples were detected, with a total positive detection rate of 50.57%. The detection rates of bacterial, viral and mixed infection were 25.14%, 21.02% and 4.40%, respectively. Among the pathogens detected, DEC accounted for the highest (17.61%, 124/704), followed by norovirus (16.48%, 116/704), rotavirus (6.39%, 45/704), SAL (5.97%, 42/704) and Campylobacter (3.84%, 27/704). DEC detected were mainly enteroaggregative Escherichia coli and enterotoxigenic Escherichia coli, with no detection of Vibrio cholerae, Shigella and YE. The highest total pathogen detection rate was observed from June to September, and the detection peaks of norovirus were from March to June and from October to December, whereas that of DEC was from June to October. The detection rate of rotavirus peaked from January to February, but which was not detected between 2020‒2023. The SAL positive rate peak was in September, whereas that of Campylobacter was from July to September. ConclusionThe main pathogens detected in Fengxian District from 2013‒2019 are DEC, norovirus, rotavirus, SAL and Campylobacter. Different pathogens have different detection peaks, with bacteria predominating in summer and viruses in winter and spring. Prevention and control measures should be carried out according to the epidemiological characteristics of different seasons. 
		                        		
		                        		
		                        		
		                        	
5.Integrated Transcriptomic Landscape and Deep Learning Based Survival Prediction in Uterine Sarcomas
Yaolin SONG ; Guangqi LI ; Zhenqi ZHANG ; Yinbo LIU ; Huiqing JIA ; Chao ZHANG ; Jigang WANG ; Yanjiao HU ; Fengyun HAO ; Xianglan LIU ; Yunxia XIE ; Ding MA ; Ganghua LI ; Zaixian TAI ; Xiaoming XING
Cancer Research and Treatment 2025;57(1):250-266
		                        		
		                        			 Purpose:
		                        			The genomic characteristics of uterine sarcomas have not been fully elucidated. This study aimed to explore the genomic landscape of the uterine sarcomas (USs). 
		                        		
		                        			Materials and Methods:
		                        			Comprehensive genomic analysis through RNA-sequencing was conducted. Gene fusion, differentially expressed genes (DEGs), signaling pathway enrichment, immune cell infiltration, and prognosis were analyzed. A deep learning model was constructed to predict the survival of US patients. 
		                        		
		                        			Results:
		                        			A total of 71 US samples were examined, including 47 endometrial stromal sarcomas (ESS), 18 uterine leiomyosarcomas (uLMS), three adenosarcomas, two carcinosarcomas, and one uterine tumor resembling an ovarian sex-cord tumor. ESS (including high-grade ESS [HGESS] and low-grade ESS [LGESS]) and uLMS showed distinct gene fusion signatures; a novel gene fusion site, MRPS18A–PDC-AS1 could be a potential diagnostic marker for the pathology differential diagnosis of uLMS and ESS; 797 and 477 uterine sarcoma DEGs (uDEGs) were identified in the ESS vs. uLMS and HGESS vs. LGESS groups, respectively. The uDEGs were enriched in multiple pathways. Fifteen genes including LAMB4 were confirmed with prognostic value in USs; immune infiltration analysis revealed the prognositic value of myeloid dendritic cells, plasmacytoid dendritic cells, natural killer cells, macrophage M1, monocytes and hematopoietic stem cells in USs; the deep learning model named Max-Mean Non-Local multi-instance learning (MMN-MIL) showed satisfactory performance in predicting the survival of US patients, with the area under the receiver operating curve curve reached 0.909 and accuracy achieved 0.804. 
		                        		
		                        			Conclusion
		                        			USs harbored distinct gene fusion characteristics and gene expression features between HGESS, LGESS, and uLMS. The MMN-MIL model could effectively predict the survival of US patients. 
		                        		
		                        		
		                        		
		                        	
6.Evaluation index system of cervical cancer prevention and control literacy based on Delphi method
ZHOU Xuan ; WU Miaomiao ; HE Yiqing ; SU Fang ; DING Jinxia ; XIE Lunfang
Journal of Preventive Medicine 2025;37(4):413-416,420
		                        		
		                        			Objective:
		                        			To construct an evaluation index system of cervical cancer prevention and control literacy, so as to provide an assessment tool for cervical cancer prevention and control literacy.
		                        		
		                        			Methods:
		                        			The preliminary framework for cervical cancer prevention and control literacy was designed based on literature review. Twenty-one experts with both theoretical and practical experience in cervical cancer prevention and control were invited to participate in two rounds of Delphi consultation. The weights of indicators were determined by the percentage weighting method and product method, and the response rate, authority level, opinion concentration degree, and coordination degree of experts were evaluated.
		                        		
		                        			Results:
		                        			Twenty-one experts participated in the consultation, including 3 males and 18 females. There were 11 experts with a doctor's degree, 7 with a master's degree and 3 with a bachelor's degree. All of them had senior professional titles and had more than 10 years of working experience. The recovery rates of the two rounds of consultations were 100.00% and 95.24%, the authority coefficients were 0.963 and 0.948, and Kendall's coefficients of concordance were 0.175 and 0.148 (both P<0.05), respectively. The final cervical cancer prevention and control literacy evaluation index system included 3 primary indicators (basic knowledge and concepts: 0.334; healthy lifestyle and behaviors: 0.338; basic skills: 0.328), 12 secondary indicators, with "capability to accurately acquire, comprehend, evaluate and apply health information" having the highest weight (0.166), and 51 tertiary indicators, with "HPV vaccination" (0.086), "consulting on relevant issues" (0.082), and "expressing personal perspectives" (0.080) having relatively higher weights.
		                        		
		                        			Conclusion
		                        			The evaluation index system of cervical cancer prevention and control literacy serves as a valid assessment tool for women of appropriate age, providing the reference for developing targeted health education to enhance cervical cancer prevention and control literacy.
		                        		
		                        		
		                        		
		                        	
8.Mechanism of Yishen Tongluo Prescription in Inhibiting Endoplasmic Reticulum Stress and Improving Apoptosis of Renal Tubular Epithelial Cells Based on PERK/ATF4/CHOP
Xuan SU ; Liang ZHAO ; Mengmeng WANG ; Jing DING ; Zhenqiang ZHANG ; Xiaowei ZHANG ; Jiangyan XU ; Zhishen XIE
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(2):26-36
		                        		
		                        			
		                        			ObjectiveTo investigate the effect of Yishen Tongluo prescription (YSTLP) on apoptosis of renal tubular epithelial cells and explore the mechanism based on endoplasmic reticulum stress pathway of protein kinase R-like endoplasmic reticulum kinase (PERK)/activating transcription factor 4 (ATF4)/transcription factor C/EBP homologous protein (CHOP). MethodThe db/db mice were randomly divided into model group, valsartan group (10 mg·kg-1), and low, middle, high-dose YSTLP groups (1, 2.5, 5 g·kg-1). Samples were collected after eight weeks of drug intervention. In addition, db/m mice in the same litter served as the control group. Human renal tubular epithelial cells (HK-2) were cultured in vitro and divided into the control group, advanced glycated end-product (AGE) group, and AGE + low, middle, and high-dose YSTLP groups (100, 200, 400 mg·L-1). TdT-mediated dUTP nick end labeling (TUNEL) staining was used to detect the apoptosis rate of HK-2 cells. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay was conducted to detect the viability of HK-2 cells. Calcium fluorescence probe staining and luciferase reporter gene method were adopted to detect the luciferase activity of folded protein response element (UPRE) and endoplasmic reticulum stress. Immunohistochemical (IHC) analysis was carried out to measure the protein expressions of phosphorylated PKR (p-PERK), CHOP, and ATF4. Real-time polymerase chain reaction (Real-time PCR) was used to measure the mRNA expression levels of CHOP and X-box binding protein 1 (XBP1) in mouse kidney and HK-2 cells. Western blot was used to detect the protein expression level of p-PERK, PERK, CHOP, ATF4, B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), and cleaved Caspase-3 in mouse kidney and HK-2 cells. ResultIn the cellular assay, HK-2 cell viability was significantly reduced, and the apoptosis rate was elevated in the AGE group compared with the control group (P<0.01). The mRNA and protein expression levels of apoptosis-related factor Bcl-2 were significantly reduced (P<0.01), and those of Bax were significantly increased (P<0.01). The protein expression level of cleaved Caspase-3 was significantly increased (P<0.01). Compared with the AGE group, YSTLP administration treatment resulted in elevated cell viability and reduced apoptosis rate (P<0.01). The mRNA and protein expression levels of Bcl-2 were significantly elevated in a time- and dose-dependent manner (P<0.01), and those of Bax were significantly reduced in a time- and dose-dependent manner. The protein expression level of cleaved Caspase-3 was significantly reduced in a time- and dose-dependent manner (P<0.01). The intracellular Ca2+ imbalance and UPRE luciferase fluorescence intensity were increased in the AGE group compared with the control group (P<0.01). The mRNA levels of endoplasmic reticulum stress-related factors CHOP and XBP1 were significantly increased (P<0.01), and the protein expression levels of p-PERK, CHOP, and ATF4 were significantly increased (P<0.05). Compared with the AGE group, YSTLP effectively improved intracellular Ca2+ imbalance in HK-2 cells and decreased UPRE luciferase fluorescence intensity in a dose-dependent manner (P<0.01). It reduced the mRNA levels of endoplasmic reticulum stress-related factors CHOP and XBP1 (P<0.01) and the protein expression levels of intracellular p-PERK, CHOP, and ATF4 in a dose- and time-dependent manner (P<0.01). In animal experiments, the protein expression level of Bcl-2 was significantly reduced(P<0.01), and that of cleaved Caspase-3 and Bax was significantly increased in the model group compared with the control group (P<0.05). The protein expression level of Bcl-2 was dose-dependently elevated, and that of cleaved Caspase-3 and Bax was dose-dependently decreased in the YSTLP groups compared with the model group (P<0.01). Compared with the control group, the mRNA expression levels of CHOP and XBP1 were significantly elevated in the model group (P<0.05, P<0.01), and the protein expression levels of p-PERK, CHOP, and ATF4 were significantly increased (P<0.05). Compared with the model group, YSTLP significantly decreased the mRNA expression levels of CHOP and XBP1 (P<0.01) and the protein expression levels of p-PERK, CHOP, and ATF4 (P<0.01). ConclusionYSTLP can effectively inhibit endoplasmic reticulum stress and improve apoptosis of renal tubular epithelial cells, and its mechanism may be related to the regulation of the PERK/AFT4/CHOP pathway. 
		                        		
		                        		
		                        		
		                        	
9.Application value of venous excess ultrasound score (VExUS Score) in patients with sepsis complicated acute kidney injury
Wei DA ; Tiantian ZHU ; Xiaobo WANG ; Peipei LIANG ; Xiaodong XIE ; Rui CHEN ; Ran LI ; Zhenxing DING ; Hong ZHANG
Chinese Journal of Emergency Medicine 2024;33(3):312-316
		                        		
		                        			
		                        			Objective:To evaluate the effect of venous excess ultrasound score (VExUS Score) in the acute kidney injury(AKI) in Patients with sepsis, so as to reduce the risk of disease and improve the prognosis of patients.Methods:This experiment was a single-center prospective cohort study. Include septic patients with AKI who were admitted to the Department of Emergency Intensive Care Unit of the First Affiliated Hospital of Anhui Medical University from February 2022 to February 2023, Those with inadequate window, inferior vena cava (IVC) thrombus, age<18 years and known case of cirrhosis with portal hypertension were excluded from the study. Patients underwent ultrasound examination with serial determination till AKI resolved or patient is initiated on dialysis.Results:Totally 86 patients were enrolled for the study. The mean age was (60.43±15.48) with 50 (58.1%) males. Mean sequential organ failure assessment (SOFA) score was (6.23±1.87). 38 patients (44.2%) were in AKI stage 1, while 24 patients (27.9%) were in AKI stage 2 and stage 3 each. 52 patients (60.5%) had VExUS grade Ⅲ. Resolution of AKI injury showed significant correlation with improvement in VExUS grade ( p value 0.003). Similarly, there was significant association between changes in VExUS grade and fluid balance ( p value 0.005). There was no correlation between central venous pressure (CVP), left ventricular function, and right ventricular function with change in VExUS grade. Conclusions:The study shows a significant correlation between the VExUS Score and AKI staging, With improvement in kidney function, there is decline in the VExUS grade as well. Moreover VExUS Score might reliably demonstrate venous congestion and aid in the clinical decision to perform fluid removal.
		                        		
		                        		
		                        		
		                        	
10.Effect Evaluation of Multidisciplinary Collaborative Diagnosis and Treatment Model for Children with Brain Injury
Xiongwu YU ; Yunli ZHOU ; Zhiyong DING ; Chaohong WANG ; Zeyi XIE ; Hongna LU ; Hua JIN
Journal of Kunming Medical University 2024;45(1):156-162
		                        		
		                        			
		                        			Objective To summarize the experience of multi-disciplinary team(MDT)in the pediatric department of Qujing Maternal and Child Health Hospital,and to evaluate the effectiveness of MDT on neonatal brain injury.Methods The clinical data of children with brain injury and treated in the pediatrics department of Qujing Maternal and Child Health Hospital from November 2019 to April 2023 were collected.The children with brain injury and treated from October 2019 to June 2020 were regarded as the non-MDT group,and the children with brain injury and treated from July 2020 to April 2023 were regarded as the MDT group for comparative analysis.Chi-square test/t-test was used to compare and analyze the clinical data of the two groups.Results Among the 890 cases of pediatric brain injury,there were 519 males and 371 females.The median and quartiles of the age distribution for the two groups were as follows:MDT group 2.00(0.82,5.00)years and non-MDT group 1.00(1.00,4.00)years.Craniocerebral injury was the main type of brain injury in both groups,in addition,among children with craniocerebral injury and intracranial hemorrhage,the cure rate of MDT group was higher than that of non-MDT group,and the difference was statistically significant(P<0.05).Among the 405 children in MDT group,154(38.0%)underwent the surgery,while among the 485 children in non-MDT group,121(24.9%)underwent the surgery.The difference was statistically significant(P<0.05).23.2% of children in MDT group were in critical condition during the hospitalization,which was significantly lower than that in non-MDT group(30.5%),and the difference was statistically significant(P<0.05).The unhealed rate of MDT group(2.0%)was also significantly lower than that of non-MDT group(5.6%),the cure rate of MDT group(40.5%)was significantly higher than that of non-MDT group(34.4%),and there was a statistically significant difference(P<0.05).The expense of treatment,medicine and sanitary materials in MDT group were lower than those in non-MDT group,and the differences were statistically significant(P<0.05).The multivariate Logistic regression model analysis of the cure rate of children with brain injury showed that the MDT model could effectively improve the cure rate of children with brain injury(RR = 1.513,95% CI = 1.134-2.020).The results of multiple linear regression model analysis showed that there was no statistical difference in the effect of MDT on the actual hospitalization days of children(P>0.05).Conclusion Using MDT model to diagnose and treat children with brain injury is helpful to improve the cure rate,reduce the risk of children's disease aggravation,and achieve the significant therapeutic effects in children with brain injury.MDT model is worth popularizing and applying in children with brain injury.
		                        		
		                        		
		                        		
		                        	
            

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