1.Mechanism of Qishen Yiqi Dropping Pills in regulating gut microbiota and ROS/TXNIP/NLRP3 signaling pathway to improve chronic heart failure in rats
Lifei LYU ; Tingting ZHU ; Fan DING ; Yingdong LU ; Xiangning CUI
Journal of Beijing University of Traditional Chinese Medicine 2025;48(3):354-369
Objective:
This study explored the regulatory effects of QiShen Yiqi Dropping Pills (QSYQ) on chronic heart failure (CHF) in rats and their related mechanisms based on the gut microbiota and reactive oxygen species (ROS)/thioredoxin interacting protein (TXNIP)/NOD-like receptor protein 3 (NLRP3) signaling pathway.
Methods:
Sixty-five SPF-grade male SD rats were used to establish a CHF model through subcutaneous multiple injections of isoproterenol (ISO) combined with exhaustion and food control methods. The modeled rats were randomly divided into model, captopril (5.30 mg/kg), and QSYQ low-, medium-, and high-dose groups (0.08, 0.16, and 0.32 g/kg, respectively), with 11 rats per group, plus a blank group of seven rats. The medication groups were given corresponding drugs by gavage, whereas the blank and model groups were administered an equivalent volume of purified water continuously for four weeks. Rat heart function was assessed via transthoracic echocardiography, and myocardial tissue pathology changes were observed through hematoxylin and eosin staining. Serum levels of brain natriuretic peptide (BNP), lipopolysaccharide (LPS), interleukin-18 (IL-18), and interleukin-1β (IL-1β) were measured using an enzyme-linked immunosorbent assay. Automated biochemical analyzers were used to determine creatine kinase (CK), lactate dehydrogenase (LDH), and MB isoenzyme of creatine kinase (CK-MB) content. Myocardial ROS levels were examined using flow cytometry; myocardial TXNIP and NLRP3 expression were detected using immunohistochemistry. Real-time qPCR and Western blotting were used to examine myocardial mRNA and protein expression of TXNIP, NLRP3, apoptosis-related spot-like protein (ASC), caspase-1, and IL-1β, as well as myocardial thioredoxin (Trx) and colonic tight junction proteins (zonula occludens-1, ZO-1), occludin, and claudin-5. Differences in the gut microbiota of the blank, model, and QSYQ high-dose groups were determined using high-throughput 16S rDNA sequencing.
Results:
Compared to the blank group, the model group exhibited significantly reduced left ventricular ejection fraction (LVEF) and left ventricular fraction shortening (LVFS) (P<0.01); increased serum BNP, LPS, IL-18, and IL-1β (P<0.01) levels; increased CK, LDH, and CK-MB (P<0.01) contents; visible myocardial tissue fibrous edema, wavy appearance, cytoplasmic loosening, round vacuolar degeneration, local tissue fibrous dissolution replaced by proliferative connective tissue, accompanied by inflammatory cell infiltration; significantly increased myocardial ROS levels (P<0.01); and significantly increased myocardial TXNIP and NLRP3 expression (P<0.01). TXNIP, NLRP3, ASC, caspase-1, and IL-1β mRNA and protein expression were significantly increased (P<0.05, P<0.01, respectively), whereas Trx, ZO-1, occludin, and claudin-5 expression was significantly decreased (P<0.01). Compared to the model group, the QSYQ high-dose group showed the most significant changes (P<0.05, P<0.01), with significant increases in LVEF and LVFS (P<0.01); significant decreases in serum BNP, LPS, IL-18, and IL-1β levels (P<0.01); significant reductions in CK, LDH, and CK-MB content (P<0.01); improved myocardial tissue damage; significantly decreased myocardial ROS levels (P<0.01); and significantly reduced myocardial TXNIP and NLRP3 expression (P<0.01). TXNIP, NLRP3, ASC, caspase-1, and IL-1β mRNA and protein expression were significantly decreased (P<0.05, P<0.01), whereas Trx, ZO-1, occludin, and claudin-5 expression was significantly increased (P<0.01). 16S rDNA sequencing results confirmed that the gut microbiota of rats changed after modeling and drug intervention, with significant differences in both α- and β-diversity. Compared to the blank group, at the family level, the abundance of Oscillospiraceae decreased (P<0.05), whereas the abundance of Lactobacillaceae increased. At the species level, the abundance of Segatella copri and Treponema succinifaciens increased, whereas the abundance of Kineothrix alysoides (P<0.05), Ruminococcus callidus, and Prevotellamassilia timonensis decreased. Compared to the model group, at the family level, the abundance of Oscillospiraceae increased (P<0.05) in the QSYQ high-dose group, whereas the abundance of Lactobacillaceae decreased. At the species level, the abundance of Segatella copri and Treponema succinifaciens decreased, whereas the abundance of Kineothrix alysoides increased (P<0.05).
Conclusion
QSYQ can regulate the relative abundance of symbiotic bacteria Kineothrix alysoides in the intestines, reduce serum LPS levels, inhibit the ROS/TXNIP/NLRP3 signaling pathway, and improve inflammatory responses, thereby exerting therapeutic effects on CHF.
2.Distribution of Traditional Chinese Medicine Syndrome Elements in Different Risk Populations of Heart Failure Complicated with Type 2 Diabetes: A Retrospective Study Based on Nomogram Model and Factor Analysis
Tingting LI ; Zhipeng YAN ; Yajie FAN ; Wenxiu LI ; Wenyu SHANG ; Yongchun LIANG ; Yiming ZUO ; Yuxin KANG ; Boyu ZHU ; Junping ZHANG
Journal of Traditional Chinese Medicine 2025;66(11):1140-1146
ObjectiveTo analyze the distribution characteristics of traditional Chinese medicine (TCM) syndrome elements in different risk populations of heart failure complicated with type 2 diabetes. MethodsClinical data of 675 type 2 diabetes patients were retrospectively collected. Lasso-multivariate Logistic regression was used to construct a clinical prediction nomogram model. Based on this, 441 non-heart failure patients were divided into a low-risk group (325 cases) and a high-risk group (116 cases) according to the median risk score of heart failure complicated with type 2 diabetes. TCM diagnostic information (four diagnostic methods) was collected for both groups, and factor analysis was applied to summarize the distribution of TCM syndrome elements in different risk populations. ResultsLasso-multivariate Logistic regression analysis identified age, disease duration, coronary heart disease, old myocardial infarction, arrhythmia, absolute neutrophil count, activated partial thromboplastin time, and α-hydroxybutyrate dehydrogenase as independent risk factors for heart failure complicated with type 2 diabetes. These were used as final predictive factors to construct the nomogram model. Model validation results showed that the area under the curve (AUC) of the receiver operating characteristic (ROC) curve for the modeling group and validation group were 0.934 and 0.935, respectively. The Hosmer-Lemeshow test (modeling group P = 0.996, validation group P = 0.121) indicated good model discrimination. Decision curve analysis showed that the curves for All and None crossed in the upper right corner, indicating high clinical utility. The low-risk and high-risk groups each obtained 14 common factors. Preliminary analysis revealed that the main disease elements in the low-risk group were qi deficiency (175 cases, 53.85%), dampness (118 cases, 36.31%), and heat (118 cases, 36.31%), with the primary locations in the spleen (125 cases, 38.46%) and lungs (99 cases, 30.46%). In the high-risk group, the main disease elements were yang deficiency (73 cases, 62.93%), blood stasis (68 cases, 58.62%), and heat (49 cases, 42.24%), with the primary locations in the kidney (84 cases, 72.41%) and heart (70 cases, 60.34%). ConclusionThe overall disease characteristics in different risk populations of type 2 diabetes patients with heart failure are a combination of deficiency and excess, with deficiency being predominant. Deficiency and heat are present throughout. The low-risk population mainly shows qi deficiency with dampness and heat, related to the spleen and lungs. The high-risk population shows yang deficiency with blood stasis and heat, related to the kidneys and heart.
3.Effect of Qigui Didang Decoction in Improving Metabolic Memory of Diabetic Nephropathy Through Sirt1/p53/NF-κB p65 Pathway
Tingting HU ; Lifei FAN ; Yuqin GUO ; Min LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(18):20-29
ObjectiveTo explore the effect and mechanism of Qigui Didang decoction, formulated based on the principle of Tonifying Deficiency and Unblocking Collaterals, on improving metabolic memory of db/db mice with diabetic nephropathy (DN) through silent information regulator 1 signal regulator 1 (Sirt1)/p53/nuclear factor kappa-B (NF-κB) p65 pathway. MethodsFifteen db/db mice were randomly divided into model group (10 mL·kg-1·d-1), resveratrol group (20 mg·kg-1·d-1), and Qigui Didang decoction group (3.34 g·kg-1·d-1) Another five db/m mice were selected as the normal group (10 mL·kg-1·d-1). After the intervention, the kidney weight of each group was measured, and the kidney index (KI) was calculated. Fasting blood glucose (FBG), creatinine (CRE), β2-microglobulin (β2-MG), blood urea nitrogen (BUN), and cystatin C (CysC) were measured. Renal pathology was observed by hematoxylin-eosin (HE) staining and Masson staining. The mRNA and protein expression levels of Sirt1, NF-κB, tumor suppressor gene p53, interleukin-1β (IL-1β), and cysteine aspartate protease-3 (Caspase-3) were detected using real-time quantitative polymerase chain reaction (Real-time PCR) and Western blot. ResultsCompared with the normal group, the model group showed disordered renal structure, obvious renal damage, and markedly elevated levels of renal function indexes (CRE, β2-MG, BUN, and CysC) (P<0.01). The KI and blood glucose were significantly increased (P<0.01), while Sirt1 expression was markedly decreased (P<0.01). Expression levels of NF-κB p65, p53, IL-1β, and Caspase-3 were increased significantly (P<0.05). Compared with those in the model group, DN mice treated with Qigui Didang decoction exhibited significantly decreased FBG, improved renal function, and markedly decreased KI (P<0.01), along with reduced CRE, β2-MG, BUN, and CysC levels (P<0.05). Protein expression of Sirt1 was significantly upregulated (P<0.05), while that of NF-κB p65, p53, IL-1β, and Caspase-3 was markedly decreased (P<0.05). The mRNA expression levels of NF-κB p65, p53, IL-1β, and Caspase-3 were significantly decreased (P<0.05). The staining results indicate improved renal fibrosis, significantly decreased fiber deposition (P<0.05), and less inflammatory infiltration in the Qigui Didang decoction group. ConclusionThe findings suggest that Qigui Didang decoction can alleviate the metabolic memory effect of DN, thereby inhibiting renal cell apoptosis and inflammatory response in mice, and improving renal function. The mechanism of action is closely related to the Sirt1/p53/NF-κB p65 signaling pathway.
4.Survey on human T-lymphotropic virus infection among blood donors in Hunan province
Binbin ZOU ; Qing HU ; Ni SUN ; Xiangmei KANG ; Tingting HU ; Fei FAN ; Feixue ZHAO
Chinese Journal of Blood Transfusion 2025;38(8):1077-1082
Objective: To investigate the prevalence of human T-lymphotropic virus (HTLV) infection among blood donors in Hunan Province from 2022 to 2024. Methods: A total of 1 830 342 blood donors from 14 prefecture-level blood centers in Hunan Province over the past three years were screened for anti-HTLV-Ⅰ/Ⅱ using enzyme-linked immunosorbent assay (ELISA). Initially reactive samples were further tested with Line Immunoassay (LIA
)/MP-Western blot and RT-PCR nucleic acid test for confirmation. Blood donors confirmed positive for HTLV were tracked and followed up. Results: From 2022 to 2024, the initial ELISA reactive rate for anti-HTLV-I/II among blood donors in Hunan Province was 1.36 per 10 000 (249/1 830 342). The confirmed positive rate was 0.20 per 10 000 (37/1 830 342), accounting for 14.86% of the initially reactive donors. The follow-up success rate for confirmed HTLV-positive blood donors was only 18.92%, while that for HTLV-indeterminate donors was 54.17%. Conclusion: The confirmed HTLV infection rates in Yueyang, Loudi, Shaoyang, Yiyang, and Zhuzhou cities were higher than the provincial (0.20 per 10 000). Chenzhou, Yongzhou, Zhangjiajie, and Xiangxi were identified as low prevalence areas, with an infection rate of 0. The overall follow-up success rate was low, indicating significant difficulties and bottlenecks in follow-up work. The comprehensive screening for HTLV and follow-up studies in Hunan provide valuable data to further improve blood safety testing strategies and risk warning mechanisms.
5.Xujiang Xie's bloodletting therapy combined with Qingyan Lige decoction for acute pharyngitis with lung-stomach heat accumulation: a randomized controlled trial.
Xinhua FAN ; Minfang YUAN ; Guohua LI ; Tingting KANG ; Peiling LI ; Qiang XIE
Chinese Acupuncture & Moxibustion 2025;45(11):1565-1570
OBJECTIVE:
To observe the clinical efficacy of Xujiang Xie's bloodletting therapy combined with Qingyan Lige decoction on acute pharyngitis with lung-stomach heat accumulation.
METHODS:
A total of 88 patients with acute pharyngitis of lung-stomach heat accumulation were randomly divided into an observation group (44 cases, 4 cases dropped out) and a control group (44 cases, 4 cases dropped out). The control group was treated with oral Qingyan Lige decoction, 150 mL each time, twice a day for 6 continuous days. On the basis of the treatment in the control group, Xujiang Xie's bloodletting therapy was applied at bilateral Shaoshang (LU11), Shangyang (LI1), and Erjian (EX-HN6) in the observation group, 0.1-0.5 mL of bloodletting per site, once every other day for 3 times in total. The TCM symptom and sign score, complete blood count (white blood cell [WBC] count, neutrophilic granulocyte percentage [NE%]), inflammation indexes (serum levels of C-reactive protein[CRP], interleukin[IL]-1β, IL-6, tumor necrosis factor [TNF]-α) and immune indexes (??, ??, ??) of the two groups were observed before treatment and after 6 days of treatment, and the clinical efficacy was evaluated.
RESULTS:
After 6 days of treatment, the sore throat scores, redness and swelling scores of pharyngeal mucosa and uvula, pharyngeal dry and burning scores, hyperemia scores of posterior pharyngeal lymphoid follicles, chill and fever scores, total scores of TCM symptom and sign, WBC count, NE%, CRP, IL-1β, IL-6, TNF-α and ?? in both groups were decreased compared with those before treatment (P<0.05), the above indexes in the observation group were lower than those in the control group (P<0.01, P<0.05, P<0.001). After 6 days of treatment, the levels of ?? and ?? in both groups were increased compared with those before treatment (P<0.05), and the above indexes in the observation group were higher than those in the control group (P<0.001). The total effective rate of the observation group was 95.0% (38/40), which was higher than 90.0% (36/40) in the control group (P<0.001).
CONCLUSION
Xujiang Xie's bloodletting therapy combined with Qingyan Lige decoction could improve the symptoms in patients with acute pharyngitis of lung-stomach heat accumulation, inhibit inflammatory response and improve immune function.
Humans
;
Drugs, Chinese Herbal/administration & dosage*
;
Male
;
Female
;
Pharyngitis/drug therapy*
;
Adult
;
Middle Aged
;
Bloodletting
;
Young Adult
;
Lung/drug effects*
;
Combined Modality Therapy
;
Interleukin-6
;
Adolescent
;
Tumor Necrosis Factor-alpha
;
Acute Disease/therapy*
;
Treatment Outcome
7.Gynostemma pentaphyllum ethanol extract ameliorates motor dysfunction in a Parkinson's disease mouse model through inhibiting neuronal apoptosis.
Tingting ZHAO ; Lanqiao HE ; Sen YAN ; Pengyu FAN ; Chong ZHANG ; Linghui ZENG
Journal of Zhejiang University. Medical sciences 2025;54(1):49-57
OBJECTIVES:
To investigate the protective effects and underlying mechanisms of Gynostemma pentaphyllum (GP)ethanol extract on motor dysfunction in a mouse model of Parkinson's disease (PD).
METHODS:
Eighty C57BL/6 male mice were randomly divided into five groups: control group, model group, levodopa group (positive control group), low-dose GP group, and high-dose GP group, with 16 mice per group. The PD model was induced by injection of 6-hydroxydopamine into the substantia nigra pars reticulata of the mice. Two weeks after 6-hydroxydopamine, positive control group received intraperitoneal injection of levodopa 10 mg·kg-1·d-1, while low-dose GP and high-dose GP groups received GP extract 100 or 200 mg·kg-1·d-1 orally for three weeks. After a 3-week-treatment, the effects of GP on motor dysfunction in 6-hydroxydopamine-induced PD were assessed using open field and CatWalk gait tests, while the effects on muscle strength were evaluated by forelimb grip strength. Immunofluorescence staining was used to detect the number of tyrosine hydroxylase (TH) positive neurons. The levels of dopamine and serotonin in the midbrain were determined by enzyme-linked immunosorbent assay. In addition, Western blotting was performed to detect the expression of mitogen-activated protein kinase (MAPK) family proteins such as p-extracellular signal-regulated kinase (ERK)1/2, p-p38 and p-c-Jun N-terminal kinase (JNK)1/2, and mitochondrial apoptosis pathway proteins such as B-cell lymphoma (Bcl)-2, Bcl-2 associated X protein (Bax), and cleaved-cysteine aspartic acid specific protease (caspase)-3.
RESULTS:
Behavioral experiments showed that GP significantly improved the spontaneous activity and motor coordination of PD mice (P<0.05). The forelimb grip strength was also increased by GP treatment (P<0.05), compared to the PD model group. In addition, compared with the model group, the number of TH-positive neurons in substantia nigra pars reticulata region, the levels of dopamine and serotonin in midbrain and the expression of p-ERK1/2 were significantly increased by GP treatment (all P<0.05), whereas the expression of p-p38 and p-JNK1/2, the ratio of Bax/Bcl-2 and cleaved-caspase-3/caspase-3 were significantly decreased (all P<0.05).
CONCLUSIONS
The results indicate that GP might increase dopamine and serotonin levels in the midbrain and promote the survival of dopaminergic neurons in substantia nigra pars reticulata by regulating the expression of phosphorylation of MAPK family proteins and the expression of mitochondrial apoptosis-related proteins, thereby ameliorating motor deficits in PD mice.
Animals
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Mice
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Male
;
Gynostemma/chemistry*
;
Mice, Inbred C57BL
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Apoptosis/drug effects*
;
Plant Extracts/therapeutic use*
;
Parkinson Disease/metabolism*
;
Disease Models, Animal
;
Neurons/pathology*
8.Exploration and Practice of Performance Evaluation System for Large Medical Equipment Based on Internet of Things Technology.
Chang SU ; Caixian ZHENG ; Linling ZHANG ; Yunming SHEN ; Kai FAN ; Tingting DONG ; Hangyan ZHAO ; Xiaofeng WANG ; Dawei QIAO ; Kun ZHENG
Chinese Journal of Medical Instrumentation 2025;49(2):191-196
Medical equipment, as an important indicator of smart hospital evaluation, plays a vital role in hospital operations. To ensure the safe and efficient operation of medical equipment, a reasonable performance evaluation system is indispensable. This study introduces a platform based on Internet of Things (IoT) technology that connects medical devices and collects data, achieving standardized and structured data processing, and supporting online operational supervision. Through the Delphi method, a performance evaluation system for large medical equipment is constructed, including 4 primary indicators and 22 secondary indicators. DICOM data acquisition devices are used to achieve functions such as efficiency analysis, benefit analysis, usage evaluation, and decision-making support for medical equipment. The study is still in its early stages, and in the future, it is expected to integrate more types of equipment, achieve rational resource allocation, and significantly impact decision-making for the development of public hospitals.
Internet of Things
;
Delphi Technique
9.Protective effect of Bufei Yishen Formula against cigarette smoke extract-induced human bronchial epithelial cell damage and its mechanism.
Zhengyuan FAN ; Zihan SHEN ; Ya LI ; Tingting SHEN ; Gaofeng LI ; Suyun LI
Journal of Southern Medical University 2025;45(7):1372-1379
OBJECTIVES:
To evaluate the protective effect of Bufei Yishen Formula (BYF) against cigarette smoke extract (CSE)-induced injuries in human bronchial epithelial BEAS-2B cells and explore the underlying mechanism.
METHODS:
BEAS-2B cells exposed to CSE were treated with normal rat serum, BYF-medicated rat serum at low or high doses, pyrrolidine dithiocarbamate (PDTC, a NF-κB inhibitor), PDTC combined with high-dose BYF-medicated serum, or S-carbomethyloysteine (S-CMC, as the positive control). CCK-8 assay was used to determine the optimal concentration and treatment time of CSE, BYF-medicated serum and S-CMC. The treated cells were examined for inflammatory factor levels in the supernatant and cellular expressions of MUC5AC and MUC5B using ELISA, cell ultrastructural changes with transmission electron microscopy, and cell apoptosis rate using flow cytometry. The expression levels of TLR4/NF‑κB pathway-associated mRNAs and proteins were determined by qRT-PCR and Western blotting.
RESULTS:
CSE exposure significantly increased secretions of IL-1β, IL-6 and TNF-α, mRNA and protein expressions of MUC5AC and MUC5B, and early and total apoptosis rates in BEAS-2B cells, where the presence of apoptotic bodies was detected. CSE also significantly enhanced the mRNA and protein expressions of TLR4, I-κB, and NF-κB and reduced mRNA and protein expressions of AQP5. Treatments of the CSE-exposed cells with BYF-medicated serum, PDTC and S-CMC all significantly lowered inflammatory factor levels, MUC5AC and MUC5B expressions, and early and total cell apoptosis rates, and partly reversed the changes in cellular ultrastructure and mRNA and protein expressions of the TLR4/NF-κB pathway, and the effects were the most conspicuous following the combined treatment with high-dose BYF-medicated serum and PDTC.
CONCLUSIONS
BYF can inhibit cell apoptosis, inflammation and mucus hypersecretion in CSE-induced BEAS-2B cells by inhibiting the TLR4/NF-κB signaling pathway.
Humans
;
Epithelial Cells/cytology*
;
Drugs, Chinese Herbal/pharmacology*
;
NF-kappa B/metabolism*
;
Bronchi/cytology*
;
Smoke/adverse effects*
;
Apoptosis/drug effects*
;
Mucin 5AC/metabolism*
;
Cell Line
;
Toll-Like Receptor 4/metabolism*
;
Mucin-5B/metabolism*
;
Signal Transduction/drug effects*
;
Nicotiana
;
Rats
;
Thiocarbamates/pharmacology*
;
Animals
10.Association between unhealthy lifestyles and diabetic dyslipidemia in occupational population and network analysis
Chunlan MA ; Bin YU ; Yunzhe FAN ; Tingting YE ; Changwei CAI ; Bo YANG ; Honglian ZENG ; Peng JIA ; Shujuan YANG
Chinese Journal of Epidemiology 2024;45(3):425-431
Objective:To understand the influence of unhealthy lifestyle on diabetic dyslipidemia and the key influencing factors in occupational population and provided scientific evidence for the prevention of diabetic dyslipidemia.Methods:Based on baseline data and follow-up data of Southwest Occupational Population Cohort from China Railway Chengdu Group Co., Ltd. during 2021. Diabetic dyslipidemia was defined as diabetes plus one or more forms of dyslipidemia, and unhealthy lifestyle factors included smoking, alcohol consumption, unhealthy dietary patterns, low physical activity, and abnormal BMI. Multivariate logistic regression model was used to analyze the relationship between unhealthy lifestyle scores and diabetic dyslipidemia, network analysis was used to find and explore the key lifestyles influencing glycolipid metabolism.Results:A total of 25 631 subjects were included. People with unhealthy lifestyle score 2 and 3 were 1.93 (95% CI: 1.31-2.86) times and 2.37 (95% CI: 1.60-3.50) times more likely to have diabetes with ≥1 forms of dyslipidemia than those with scores of 0; People with unhealthy lifestyle score 1, 2 and 3 were 1.98 (95% CI: 1.08-3.61) times, 2.87 (95% CI: 1.60-5.14) times and 3.95 (95% CI: 2.22-7.06) times more likely to have diabetes with ≥2 forms of dyslipidemia than those with score 0. Network analysis found that abnormal BMI and HDL-C were the "bridge nodes" that link unhealthy lifestyles with diabetic dyslipidemia. Conclusion:The higher the score of unhealthy lifestyle, the higher the risk for diabetic dyslipidemia, abnormal BMI and HDL-C are key factors influencing the association between unhealthy lifestyle and diabetic dyslipidemia.


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