1.Total Flavonoids from Cuscutae Semen Inhibit Depression in CUMS Mice via UCP2/TXNIP/NLRP3 Signaling Pathway
Andong SONG ; Guohua LI ; Bo YUAN ; Menghui JIA ; Zhantao LI ; Xiaoli WANG ; Long WANG ; Huiling FU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):109-119
ObjectiveTo investigate the antidepressant effects and mechanisms of total flavonoids from Cuscutae Semen (TFCC) in the mouse model of chronic unpredictable mild stress (CUMS). MethodsFifty male 4-week-old ICR mice were randomized into five groups (n=10 per group): blank control, model, Cuscutae Semen decoction (10.2 g·kg-1·d-1), paroxetine (2.6 mg·kg-1·d-1), and TFCC (173.2 mg·kg-1·d-1). The other groups except the blank control group underwent chronic unpredictable mild stress (CUMS) for 4 weeks. Behavioral assessments were conducted post-modeling. Then, the model group received distilled water (10 mL·kg-1·d-1), while treatment groups were administrated with respective agents via oral gavage (10 mL·kg-1) for 4 weeks. Depression-like behaviors were evaluated by the sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST). Hippocampal neuronal morphology was observed via hematoxylin-eosin staining, and apoptosis in the brain tissue was assessed via terminal- deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). Enzyme-linked immunosorbent assay (ELISA) was employed to measure the hippocampal levels of inflammatory cytokines [interleukin (IL)-1β, IL-6, and TNF-α)] and neurotransmitters [5-hydroxytryptamine (5-HT), dopamine (DA), and brain-derived neurotrophic factor (BDNF)], while the reactive oxygen species (ROS) levels were quantified via the DCFH-DA probe. Real-time PCR was performed to measure the mRNA levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated Speck-like protein containing a CARD (ASC), cysteinyl aspartate-specific proteinase-1 (Caspase-1), IL-1β, and inducible nitric oxide synthase (iNOS). Western blot was employed to evaluate the protein levels of NLRP3, ASC, Caspase-1, uncoupling protein 2 (UCP2), and thioredoxin-interacting protein (TXNIP). ResultsCompared with the blank control group, the model group exhibited weight loss (P<0.01), reduced sucrose preference (P<0.01), prolonged immobility time in FST and TST (P<0.01), neuron disarrangement with nuclear pyknosis in hippocampal CA3 region, increased apoptosis in the brain tissue, elevated levels of IL-1β, IL-6, and TNF-α (P<0.01), declined levels of 5-HT, DA, and BDNF (P<0.01), increased ROS accumulation (P<0.01), upregulated mRNA levels of NLRP3, ASC, Caspase-1, IL-1β, and iNOS (P<0.01), down-regulated protein level of UCP2 (P<0.01), and up-regulated protein levels of NLRP3, ASC, Caspase-1, and TXNIP (P<0.01). Compared with the model group, the interventions restored sucrose preference (P<0.01), shortened immobility time (P<0.01), repaired hippocampal neuronal structure, reduced apoptosis, lowered the levels of inflammatory cytokines (P<0.01), restored the levels of neurotransmitters (P<0.01), alleviated ROS accumulation (P<0.01), downregulated the mRNA levels of NLRP3, ASC, Caspase-1, IL-1β, and iNOS (P<0.01), upregulated the protein level of UCP2 (P<0.01), and reduced the protein levels of NLRP3, ASC, Caspase-1, and TXNIP (P<0.01). Moreover, TFCC outperformed Cuscutae Semen decoction in ameliorating depressive behaviors. TFCC excelled in neuronal repair, neurotransmitter regulation, anti-inflammatory effects, and modulation of the UCP2/TXNIP/NLRP3 pathway (P<0.05). ConclusionTFCC modulates the hippocampal UCP2/TXNIP/NLRP3 pathway to inhibit inflammasome activation, reduce oxidative stress, restore neurotransmitters, thus suppressing neuronal apoptosis and promoting the rearrangement and morphology recovery of hippocampal cells. It outperforms Cuscutae Semen decoction in the antidepressant efficacy.
2.Total Flavonoids from Cuscutae Semen Inhibit Depression in CUMS Mice via UCP2/TXNIP/NLRP3 Signaling Pathway
Andong SONG ; Guohua LI ; Bo YUAN ; Menghui JIA ; Zhantao LI ; Xiaoli WANG ; Long WANG ; Huiling FU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):109-119
ObjectiveTo investigate the antidepressant effects and mechanisms of total flavonoids from Cuscutae Semen (TFCC) in the mouse model of chronic unpredictable mild stress (CUMS). MethodsFifty male 4-week-old ICR mice were randomized into five groups (n=10 per group): blank control, model, Cuscutae Semen decoction (10.2 g·kg-1·d-1), paroxetine (2.6 mg·kg-1·d-1), and TFCC (173.2 mg·kg-1·d-1). The other groups except the blank control group underwent chronic unpredictable mild stress (CUMS) for 4 weeks. Behavioral assessments were conducted post-modeling. Then, the model group received distilled water (10 mL·kg-1·d-1), while treatment groups were administrated with respective agents via oral gavage (10 mL·kg-1) for 4 weeks. Depression-like behaviors were evaluated by the sucrose preference test (SPT), forced swimming test (FST), and tail suspension test (TST). Hippocampal neuronal morphology was observed via hematoxylin-eosin staining, and apoptosis in the brain tissue was assessed via terminal- deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL). Enzyme-linked immunosorbent assay (ELISA) was employed to measure the hippocampal levels of inflammatory cytokines [interleukin (IL)-1β, IL-6, and TNF-α)] and neurotransmitters [5-hydroxytryptamine (5-HT), dopamine (DA), and brain-derived neurotrophic factor (BDNF)], while the reactive oxygen species (ROS) levels were quantified via the DCFH-DA probe. Real-time PCR was performed to measure the mRNA levels of NOD-like receptor protein 3 (NLRP3), apoptosis-associated Speck-like protein containing a CARD (ASC), cysteinyl aspartate-specific proteinase-1 (Caspase-1), IL-1β, and inducible nitric oxide synthase (iNOS). Western blot was employed to evaluate the protein levels of NLRP3, ASC, Caspase-1, uncoupling protein 2 (UCP2), and thioredoxin-interacting protein (TXNIP). ResultsCompared with the blank control group, the model group exhibited weight loss (P<0.01), reduced sucrose preference (P<0.01), prolonged immobility time in FST and TST (P<0.01), neuron disarrangement with nuclear pyknosis in hippocampal CA3 region, increased apoptosis in the brain tissue, elevated levels of IL-1β, IL-6, and TNF-α (P<0.01), declined levels of 5-HT, DA, and BDNF (P<0.01), increased ROS accumulation (P<0.01), upregulated mRNA levels of NLRP3, ASC, Caspase-1, IL-1β, and iNOS (P<0.01), down-regulated protein level of UCP2 (P<0.01), and up-regulated protein levels of NLRP3, ASC, Caspase-1, and TXNIP (P<0.01). Compared with the model group, the interventions restored sucrose preference (P<0.01), shortened immobility time (P<0.01), repaired hippocampal neuronal structure, reduced apoptosis, lowered the levels of inflammatory cytokines (P<0.01), restored the levels of neurotransmitters (P<0.01), alleviated ROS accumulation (P<0.01), downregulated the mRNA levels of NLRP3, ASC, Caspase-1, IL-1β, and iNOS (P<0.01), upregulated the protein level of UCP2 (P<0.01), and reduced the protein levels of NLRP3, ASC, Caspase-1, and TXNIP (P<0.01). Moreover, TFCC outperformed Cuscutae Semen decoction in ameliorating depressive behaviors. TFCC excelled in neuronal repair, neurotransmitter regulation, anti-inflammatory effects, and modulation of the UCP2/TXNIP/NLRP3 pathway (P<0.05). ConclusionTFCC modulates the hippocampal UCP2/TXNIP/NLRP3 pathway to inhibit inflammasome activation, reduce oxidative stress, restore neurotransmitters, thus suppressing neuronal apoptosis and promoting the rearrangement and morphology recovery of hippocampal cells. It outperforms Cuscutae Semen decoction in the antidepressant efficacy.
3.Prevalence and factors related to overweight, obesity and hypertension comorbidities among primary and secondary school students in Ningxia
WEI Rong, LI Yuan, MA Ning, WANG Xiaoli, JIN Yanan,MA Fang,YANG Yi,CHEN Yaogeng
Chinese Journal of School Health 2024;45(12):1807-1810
Objective:
To explore the prevalence and related factors of overweight, obesity and hypertension comorbidities among children and adolescents in Ningxia, so as to provide a scientific basis for effective early health intervention in children and adolescents.
Methods:
From September 2021 to June 2022, a total of 4 577 students aged 9-16 were selected from Jinfeng District of Yinchuan City, Shapotou District of Zhongwei City, Yanchi County of Wuzhong City and Pingluo County of Shizuishan City in Ningxia by multi stage cluster random sampling method for questionnaire survey and physical measurement. The influencing factors of overweight, obesity and hypertension comorbidities in children and adolescents were investigated by Chi square test and multivariate unconditioned Logistic regression analysis with weighted complex sampling design.
Results:
The prevalence of overweight and obesity among primary and secondary school students in Ningxia was 22.87%, the prevalence of hypertension was 1.30%, and the comorbity rate of overweight, obesity and hypertension was 1.07%. Multivariate Logistic regression analysis showed that students aged 13-16 ( OR =15.66,95% CI =3.84-63.96, P <0.05) were more likely to suffer from overweight, obesity and hypertension than students aged 9-12. The students of insufficient sleep duration ( OR =5.47, 95% CI =1.73-17.33, P <0.05) had higher levels of overweight, obesity and hypertension comorbidities than those of adequate sleep duration. Students who had breakfast 1 to 7 times a week ( OR =0.08, 95% CI =0.02-0.37) had lower incidence than those who had breakfast once a week ( P <0.05).
Conclusions
Age, sleep time and breakfast frequency are all related factors of overweight, obesity and hypertension co morbidity among primary and secondary school students in Ningxia. Close attention should be paid to students aged 9-12 years with insufficient sleep time and fasting in the morning, and carry out scientific education and prevention and control interventions should be carried out.
5.The Multicenter Cross-sectional Study on the Distribution Characteristics of Traditional Chinese Medicine Syndrome Elements in Type 2 Diabetes Macroangiopathy
Yulin LENG ; Hong GAO ; Xiaoxu FU ; Gang XU ; Hongyan XIE ; Xingwei ZHUO ; Xiaoqin ZHOU ; Yi YANG ; Xiaoli YUAN ; Zhibiao WANG ; Chunguang XIE
Journal of Traditional Chinese Medicine 2024;65(17):1794-1801
ObjectiveTo explore the distribution characteristics of traditional Chinese medicine (TCM) syndrome elements of macroangiopathy in patients with type 2 diabetes mellitus (T2DM) and the key elements of occurrence, development and progression of disease. MethodsA multicenter cross-sectional study was conducted to enroll 445 T2DM patients from five hospitals, and according to the presence or absence of macroangiopathy, the patients were divided into a T2DM group (120 cases) and a diabetic macroangiopathy (DM) group (325 cases). Patients in DM group were divided into grade Ⅰ, Ⅱ, Ⅲ and Ⅳ according to the peripheral vascular color Doppler ultrasound results and the vascular anomalies classification standard. The general data including gender, age, duration of T2DM and body mass index (BMI) were collected, and the data of four examinations were obtained for syndrome differentiation. According to the diagnostic criteria of TCM syndrome elements, the patients can be divided into 9 patterns including qi deficiency, blood deficiency, yin deficiency, yang deficiency, qi stagnation, blood stasis, excess heat, and excess cold. The general data and distribution of TCM syndrome elements were compared between the two groups. The distribution of TCM syndrome elements in different vascular anomalies grades in the DM group was analyzed. Logistic regression analysis was used to explore the influence of various TCM syndrome elements on the occurrence of macroangiopathy in T2DM. ResultsThere was no significant difference in gender and BMI between groups (P>0.05). The age and duration of diabetes in the DM group were older and longer than those in the T2DM group (P<0.01). With the increase of age and prolonged course of disease, the severity of diabetic macroangiopathy increases gradually (P<0.05 or P<0.01). There was no significant difference in BMI and course of disease among the different TCM syndrome elements (P>0.05). The average age of patients with blood stasis syndrome was the oldest (P<0.05). There was significant difference in gender distribution between the excess heat syndrome and yin deficiency syndrome (P<0.05). A total of 240 TCM syndrome elements were extracted from the T2DM group, while 731 TCM syndrome elements extracted from the DM group. The top two high-frequency syndrome elements in the two groups were qi deficiency and yin deficiency, with a frequency of larger than 50%. The distribution of phlegm-damp syndrome and blood-stasis syndrome were significantly higher in the DM group than in the T2DM group (P<0.01). There were significant differences in the distribution of qi deficiency syndrome, yin deficiency syndrome, phlegm-damp syndrome, blood stasis syndrome, and excess heat syndrome among different grades of vascular anomalies (P<0.01); qi deficiency and yin deficiency were both high-frequency TCM syndrome elements in patients at grades 0 to Ⅲ; phlegm-damp syndrome increased in frequency with the progression of the disease from grades 0 to Ⅳ, and the frequency of blood stasis syndrome showed an overall upward trend. The frequency of phlegm-dampness syndrome increased from grades 0 to Ⅳ with the progression of the disease, and the frequency of blood stasis syndrome showed an overall upward trend. Logistic regression analysis showed that phlegm-damp syndrome and blood stasis syndrome were important TCM syndrome elements related to the vascular anomalies degree of macrovascular disease in T2DM (P<0.05 or P<0.01). ConclusionQi deficiency and yin deficiency are the basic TCM syndrome elements throughout the whole process of T2DM and diabetic macrovascular disease. Phlegm-damp and blood stasis are related to the degree of vascular anomalies in diabetic macrovascular disease and are the key TCM syndrome elements in the progression of macroangiopathy in T2DM.
6.Clinical efficacy of adjunctive perampanel in focal epilepsy patients≥12 years old
Xiaoli SHI ; Lixia LI ; Yanting LU ; Lang SHEN ; Xiangru LU ; Jinou ZHENG ; Yuan WU ; Lu YU
Chinese Journal of Neuromedicine 2024;23(1):48-54
Objective:To evaluate the clinical efficacy, tolerability and safety of adjunctive perampanel in focal epilepsy patients≥12 years old.Methods:One hundred and nineteen focal epilepsy patients≥12 years old accepted adjunctive perampanel in Department of Neurology, First Affiliated Hospital of Guangxi Medical University from July 2020 to December 2022 were chosen. At 1-3 months, 4-6 months, 7-9 months and 10-12 months after adjunctive perampanel, seizure frequency changes every 28 d, medication retention rate and adverse reactions were recorded to evaluate the clinical efficacy (a reduction in seizure frequency≥50% from baseline was defined as overall valid treatment), tolerability and safety of adjunctive perampanel. According to efficacy results after adjunctive perampanel of 4-6 months (short-term) and 10-12 months (long-term), these patients were divided into valid group and invalid group; and the influencing factors for short-term and long-term efficacy were analyzed.Results:At 1-3, 4-6, 7-9, 10-12 months after adjunctive perampanel, reduction in seizure frequency every 28 d was 66.7% (24.3%, 97.2%), 77.5% (48.6%, 100%), 94.6% (50%, 100%), 100% (70.9%, 100%), enjoying overall valid rate of 60.2% (59/98), 75.0% (7/76), 78.9% (45/57), 86.5% (32/37). The retention rate at 3, 6, 9 and 12 months after adjunctive perampanel was 85.2% (98/115), 67.9% (76/112), 54.3% (57/105), 41.1% (37/90). Adverse reactions were reported in 33 patents (27.7%), mainly with dizziness and secondly with mental symptoms. After short-term and long-term adjunctive perampanel, no significant difference was noted in gender, initial age of adjunctive perampanel, course of disease, etiology, EEG results, imaging results, number and type of combined anti-seizure drugs, or maximum dose of pirampanel between the valid group and invalid group ( P>0.05). Conclusion:Perampanel has good efficacy, tolerability and safety in adolescents and adults≥12 years old with focal epilepsy; no clear influencing factors for pirampanel valid treatment is found so far.
7.Investigation and analysis of the current status of transjugular intrahepatic portosystemic shunt treatment for portal hypertension in China
Haozhuo GUO ; Meng NIU ; Haibo SHAO ; Xinwei HAN ; Jianbo ZHAO ; Junhui SUN ; Zhuting FANG ; Bin XIONG ; Xiaoli ZHU ; Weixin REN ; Min YUAN ; Shiping YU ; Weifu LYU ; Xueqiang ZHANG ; Chunqing ZHANG ; Lei LI ; Xuefeng LUO ; Yusheng SONG ; Yilong MA ; Tong DANG ; Hua XIANG ; Yun JIN ; Hui XUE ; Guiyun JIN ; Xiao LI ; Jiarui LI ; Shi ZHOU ; Changlu YU ; Song HE ; Lei YU ; Hongmei ZU ; Jun MA ; Yanming LEI ; Ke XU ; Xiaolong QI
Chinese Journal of Radiology 2024;58(4):437-443
Objective:To investigate the current situation of the use of transjugular intrahepatic portosystemic shunt (TIPS) for portal hypertension, which should aid the development of TIPS in China.Methods:The China Portal Hypertension Alliance (CHESS) initiated this study that comprehensively investigated the basic situation of TIPS for portal hypertension in China through network research. The survey included the following: the number of surgical cases, main indications, the development of Early-TIPS, TIPS for portal vein cavernous transformation, collateral circulation embolization, intraoperative portal pressure gradient measurement, commonly used stent types, conventional anticoagulation and time, postoperative follow-up, obstacles, and the application of domestic instruments.Results:According to the survey, a total of 13 527 TIPS operations were carried out in 545 hospitals participating in the survey in 2021, and 94.1% of the hospital had the habit of routine follow-up after TIPS. Most hospitals believed that the main indications of TIPS were the control of acute bleeding (42.6%) and the prevention of rebleeding (40.7%). 48.1% of the teams carried out early or priority TIPS, 53.0% of the teams carried out TIPS for the cavernous transformation of the portal vein, and 81.0% chose routine embolization of collateral circulation during operation. Most of them used coils and biological glue as embolic materials, and 78.5% of the team routinely performed intraoperative portal pressure gradient measurements. In selecting TIPS stents, 57.1% of the hospitals woulel choose Viator-specific stents, 57.2% woulel choose conventional anticoagulation after TIPS, and the duration of anticoagulation was between 3-6 months (55.4%). The limitation of TIPS surgery was mainly due to cost (72.3%) and insufficient understanding of doctors in related departments (77.4%). Most teams accepted the domestic instruments used in TIPS (92.7%).Conclusions:This survey shows that TIPS treatment is an essential part of treating portal hypertension in China. The total number of TIPS cases is far from that of patients with portal hypertension. In the future, it is still necessary to popularize TIPS technology and further standardize surgical indications, routine operations, and instrument application.
8.Analysis of a child with developmental disorder and epilepsy due to a homozygous variant of SLC25A12 gene
Shitao WEI ; Xiaoli HUANG ; Luoxiao QIN ; Mo QIN ; Yilan ZHOU ; Bin YU ; Dejian YUAN ; Rongsong YI ; Yang TIAN
Chinese Journal of Medical Genetics 2024;41(7):830-834
Objective:To explore the genetic basis for a child featuring global developmental delay and epilepsy.Methods:A child who had presented at Guangzhou Women and Children′s Medical Center Liuzhou Hospital on February 19, 2023 was selected as the study subject. Clinical data of the child was collected. The child was subjected to whole exome sequencing, and candidate variant was validated by Sanger sequencing and bioinformatic analysis.Results:The child, an 8-month-old girl, had manifested with global developmental delay, epilepsy, and hyperlactacidemia. Cranial MRI revealed diverse hypomyelinating leukodystrophies. Electroencephalogram showed slow background activities. Genetic testing revealed that she has harbored a homozygous variant of the SLC25A12 gene, namely c. 115T>G (p.Phe39Val), for which both of her parents were heterozygous carriers. Based on the guidelines from the American College of Medical Genetics and Genomics, the variant was predicted to be of uncertain significance (PM2_Supporting+ PM3_Supporting+ PP3_Moderate+ PP4_Moderate). I-Mutant v3.0 software predicted that the variant may affect the stability of protein product. Conclusion:The homozygous c. 115T>G (p.Phe39Val) variant of the SLC25A12 gene probably underlay the pathogenesis of the disease in this child.
9.Identification of anti-Jra antibodies by serology and mass spectrometry
Zhifa LING ; Xiaoli ZENG ; Xuewen YUAN ; Wei SHEN
Chinese Journal of Blood Transfusion 2024;37(7):827-830
Objective To report the antibody specific identification process of a pregnant woman who had no history of blood transfusion but presented high-frequency anti-Jra antibodies.Methods Antibody screening and identification were performed by saline and indirect Coomb's technique(microcolumn gel card,PEG).ABO,Rh and other blood group anti-gens were identified by saline.Further antibody identification tests were performed by the reaction between cells treated with various enzymes and patient plasma.Jra antigen was identified by human anti-Jraantibody.JR blood type genotyping was per-formed by MALDI-TOF mass spectrometry detection system.Antibody titer in serum was tested.Results The patient′s blood type was O with RhD(+)and CcDEe.The plasma reacted negatively with antibody screening and identification cells by saline,but positively by indirect globulin test.The self-control was negative.The patient′s Jraantigen was negative in sero-logical tests and mass spectrometry blood type genotyping.Mass spectrometry revealed a homozygous nonsense mutation(c.376C>T)in exon4.The anti-Jra antibody titer was1∶2.Conclusion The patient developed high-frequency anti-Jraantibod-ies during pregnancy.
10.Development and validation of a nutrition-related genetic-clinical-radiological nomogram associated with behavioral and psychological symptoms in Alzheimer’s disease
Jiwei JIANG ; Yaou LIU ; Anxin WANG ; Zhizheng ZHUO ; Hanping SHI ; Xiaoli ZHANG ; Wenyi LI ; Mengfan SUN ; Shirui JIANG ; Yanli WANG ; Xinying ZOU ; Yuan ZHANG ; Ziyan JIA ; Jun XU
Chinese Medical Journal 2024;137(18):2202-2212
Background::Few evidence is available in the early prediction models of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer’s disease (AD). This study aimed to develop and validate a novel genetic-clinical-radiological nomogram for evaluating BPSD in patients with AD and explore its underlying nutritional mechanism.Methods::This retrospective study included 165 patients with AD from the Chinese Imaging, Biomarkers, and Lifestyle (CIBL) cohort between June 1, 2021, and March 31, 2022. Data on demographics, neuropsychological assessments, single-nucleotide polymorphisms of AD risk genes, and regional brain volumes were collected. A multivariate logistic regression model identified BPSD-associated factors, for subsequently constructing a diagnostic nomogram. This nomogram was internally validated through 1000-bootstrap resampling and externally validated using a time-series split based on the CIBL cohort data between June 1, 2022, and February 1, 2023. Area under receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to assess the discrimination, calibration, and clinical applicability of the nomogram.Results::Factors independently associated with BPSD were: CETP rs1800775 (odds ratio [OR] = 4.137, 95% confidence interval [CI]: 1.276-13.415, P = 0.018), decreased Mini Nutritional Assessment score (OR = 0.187, 95% CI: 0.086-0.405, P <0.001), increased caregiver burden inventory score (OR = 8.993, 95% CI: 3.830-21.119, P <0.001), and decreased brain stem volume (OR = 0.006, 95% CI: 0.001-0.191, P = 0.004). These variables were incorporated into the nomogram. The area under the ROC curve was 0.925 (95% CI: 0.884-0.967, P <0.001) in the internal validation and 0.791 (95% CI: 0.686-0.895, P <0.001) in the external validation. The calibration plots showed favorable consistency between the prediction of nomogram and actual observations, and the DCA showed that the model was clinically useful in both validations. Conclusion::A novel nomogram was established and validated based on lipid metabolism-related genes, nutritional status, and brain stem volumes, which may allow patients with AD to benefit from early triage and more intensive monitoring of BPSD.Registration::Chictr.org.cn, ChiCTR2100049131.


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