1.Yishen Tongluo Prescription Ameliorates Oxidative Stress Injury in Mouse Model of Diabetic Kidney Disease via Nrf2/HO-1/NQO1 Signaling Pathway
Yifei ZHANG ; Xuehui BAI ; Zijing CAO ; Zeyu ZHANG ; Jingyi TANG ; Junyu XI ; Shujiao ZHANG ; Shuaixing ZHANG ; Yiran XIE ; Yuqi WU ; Zhongjie LIU ; Weijing LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):41-51
ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease (DKD) via the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase 1 (NQO1) signaling pathway. MethodsSpecific pathogen-free (SPF) male C57BL/6 mice were assigned into a control group (n=10) and a modeling group (n=50). The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group, a semaglutide (40 μg·kg-1) group, and high-, medium-, and low-dose (18.2, 9.1, 4.55 g·kg-1, respectively) Yishen Tongluo prescription groups, with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured, and the kidney index (KI) was calculated. Serum levels of creatinine (SCr), blood urea nitrogen (BUN), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin, periodic acid-Schiff, periodic acid-silver methenamine, and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver fatty acid-binding protein (L-FABP), nitric oxide synthase (NOS), glutathione (GSH), total antioxidant capacity (T-AOC), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 (Keap1) and malondialdehyde (MDA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group, the DKD model group showed rises in blood glucose, 24-h urine protein, KI, SCr, BUN, and ALT levels, along with glomerular hypertrophy, renal tubular dilation, thickened basement membrane, mesangial expansion, and collagen deposition. Additionally, the model group showed elevated levels of β2-MG, NGAL, KIM-1, L-FABP, NOS, and 8-OHdG, lowered levels of GSH and T-AOC, up-regulated expression of MDA and Keap1, and down-regulated expression of Nrf2, HO-1, NQO1, and glutamate-cysteine ligase catalytic subunit (GCLC) (P<0.05). Compared with the model group, the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose, 24-h urine protein, KI, SCr, BUN, and ALT levels, along with alleviated pathological injuries in the renal tissue. In addition, the three groups showed lowered levels of β2-MG, NGAL, KIM-1, L-FABP, NOS, and 8-OHdG, elevated levels of GSH and T-AOC, down-regulated expression of MDA and Keap1, and up-regulated expression of Nrf2, HO-1, NQO1, and GCLC (P<0.05). ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway, mitigating oxidative stress, and reducing renal tubular injuries.
2.Three-Dimensional Foot Type Classification and Feature Extraction for Young Males Based on Multi-Fusion Algorithms
Xiaotian BAI ; Jingmin LIU ; Hongfeng HUO ; Pengfei WANG ; Mengyi WU ; Chong WANG ; Zeyu XING
Journal of Medical Biomechanics 2025;40(3):638-645
Objective To classify the foot types of young Chinese males,extract characteristic indicators of foot types,and construct a standard foot type database.Methods Foot type data from 1 483 healthy young male individuals were collected.Spectral clustering algorithm was utilized to categorize foot types,and a deep neural network(DNN)was employed for training the classification model.Layer-wise relevance propagation(LRP)and the correlation coefficient method were combined to extract foot type features,and the differences in various foot type characteristics were compared.Results Spectral clustering yielded 4 distinct foot type categories.Foot type 1 was characterized by a high-arched foot with a prominent big toe,inwardly rotated 5th toe,and a high heel with a wide foot;foot type 2 was characterized by a narrow foot with hallux valgus;foot type 3 was characterized by a low-arched foot with hallux valgus;foot type 4 was characterized by a high-arched foot with a prominent big toe.By integrating interpretable neural networks and the correlation coefficient method,nine indicators were extracted from 27 foot type indicators,including the heel to the sole length,hallux height,navicular bone height,lateral malleolus height,hallux valgus angle,5th toe angle,dorsal foot circumference,heel angle,and longitudinal arch angle.The classification model constructed with these extracted indicators achieved an overall discrimination accuracy rate of 93.67%.Conclusions Chinese young males can be classified into four typical foot types.By examining the rearfoot,midfoot,and forefoot regions,nine key foot morphology parameters,including length,height,circumference,and angle,can be extracted.These parameters provide both theoretical and empirical support for establishing normative data on foot morphology for Chinese young males and for advancing biomechanical researches on the foot and ankle.
3.In vitro osteogenic performance study of graphene oxide-coated titanium surfaces modified with dopamine or silane
Qinglin WU ; Yingzhen LAI ; Yanling HUANG ; Zeyu XIE ; Yanyin LIN
West China Journal of Stomatology 2025;43(3):336-345
Objective This study aimed to compare the osteogenic performance differences of titanium surface coat-ings modified by dopamine or silanized graphene oxide,and to provide a more suitable modification scheme for ti-tanium surface graphene oxide coatings.Methods Tita-nium was subjected to alkali-heat treatment and then modified with dopamine and silanization,respectively,followed by coating with graphene oxide.Control and ex-perimental groups were designed as follows:pure titanium(Ti)group;titanium after alkali-heat treatment(Ti-NaOH)group;titanium after alkali-heat treatment and silanization modification(Ti-APTES)group;titanium after alkali-heat treatment and dopamine modification(Ti-DOPA)group;titanium with silanization-modified surface decorated with gra-phene oxide(Ti-APTES/GO)group;titanium with dopamine-modified surface decorated with graphene oxide(Ti-DOPA/GO)group.The physical and chemical properties of the material surfaces were analyzed using scanning electron micros-copy(SEM),contact angle goniometer,X-ray photoelectron spectroscopy(XPS),and Raman spectrometer.The prolifera-tion and adhesion morphology of mouse embryonic osteoblast precursor cells MC3T3-E1 on the material surfaces were observed by cell viability detection and immunofluorescence staining followed by laser confocal microscopy.The effects on the osteogenic differentiation of MC3T3-E1 cells were studied by alkaline phosphatase(ALP)staining,alizarin red staining and quantification,and real-time quantitative polymerase chain reaction.Results After modification with gra-phene oxide coating,a thin-film-like structure was observed on the surface under SEM.The hydrophilicity of all experi-mental groups was improved,among which the Ti-DOPA/GO group had the best hydrophilicity.XPS and Raman spec-troscopy analysis showed that the modified materials exhibited typical D and G peaks,and XPS revealed the presence of a large number of oxygen-containing functional groups on the surface.CCK8 assay showed that all groups of materials had no cytotoxicity,and the proliferation level of the Ti-APTES/GO group was higher than that of the Ti-DOPA/GO group.Under the laser confocal microscope,the cells in the Ti-DOPA/GO and Ti-APTES/GO groups spread more fully.The Ti-DOPA/GO and Ti-APTES/GO groups had the deepest ALP staining,and the Ti-APTES/GO group had the most alizarin red-stained mineralized nodules and the highest quantitative result of alizarin red staining.In the Ti-DOPA/GO and Ti-APTES/GO groups,the expression of the early osteogenic-related gene RUNX2 reached a relatively high level,while in the expression of the late osteogenic-related genes OPN and OCN,the Ti-APTES/GO group performed better than the Ti-DOPA/GO group.Conclusion Ti-APTES/GO significantly outperformed Ti-DOPA/GO in promoting the adhesion,proliferation,and in vitro osteogenic differentiation of MC3T3-E1 cells.
4.Relationship Between Single-Leg Standing Posture Control and Ankle Plantar Flexor Muscle Stability under Visual and Proprioceptive Interference
Chong WANG ; Mengyi WU ; Pengfei WANG ; Zeyu XING ; Hongfeng HUO
Journal of Medical Biomechanics 2025;40(5):1193-1199
Objective To explore the correlation between single-leg standing posture control and ankle plantar flexor muscle stability,so as to provide a new theoretical basis for improving the ability of human posture control.Methods A total of 20 healthy male college students were randomly selected as the experimental subjects.The iBalance tester and training system was used to test the trajectory data of the center of pressure(COP)of the foot standing on one leg.The CON-TREX MJ multi-joint isokinetic test and training system was used to test the moment amplitude data during the contraction of ankle plantar flexor muscles.Univariate repeated measures variance analysis was used to analyze the standard deviation data of ankle plantar flexor moment amplitude between groups.The Pearson correlation coefficient was used to study the correlation.Results The greater the intensity of the muscle stabilization task performed by the ankle plantar flexor muscle,the greater the standard deviation of the moment amplitude.The C90 area was positively correlated with the coefficient of variation(CV)of the 10%maximum voluntary contraction(MVC)moment of ankleplantar flexor muscle(r=0.761,P<0.05)during single-leg standing without interference.The C90 area was positively correlated with the CV(r=0.632,P<0.05)of the 30%MVC moment of ankle plantar flexor muscle during single-leg standing.When the proprioception was interfered during single-leg standing,the C90 area was positively correlated with the CV(r=0.583,P<0.05)of the 20%MVC moment amplitude of ankleplantar flexor muscle.Conclusions With the increasing difficulty of muscle strength stabilization performed by the ankle plantar flexor muscles,muscle stability decreases.There is a positive correlation between ankle plantar flexor strength stability and single-leg standing posture control.Compared with the case without interference,under visual and proprioceptive interference,an additional information input is reduced or disturbed,and it is more difficult to maintain body balance,and the ankle plantar flexor muscle needs a higher muscle stability in the force mode to participate in the posture control of the human body during single-leg standing.
5.Mechanism of Yishen Tongluo Formula regulating the TLR4/MyD88/NF-κB signaling pathway to ameliorate pyroptosis in diabetic nephropathy mice
Yifei ZHANG ; Zijing CAO ; Zeyu ZHANG ; Xuehui BAI ; Jingyi TANG ; Junyu XI ; Jiayi WANG ; Yiran XIE ; Yuqi WU ; Xi GUO ; Zhongjie LIU ; Weijing LIU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):21-33
Objective:
To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway.
Methods:
Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue.
Results:
Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated.
Conclusion
Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.
6.Comparative Analysis of Oral and Gut Microbiota Composition in Children Aged 3-5 Years With Different Body Mass Indexes in Urumqi
Ting MA ; Zeyu WU ; Bingjie LIAN ; Jin ZHAO
Journal of Sichuan University (Medical Sciences) 2025;56(4):939-948
Objective To investigate the differences in oral and gut microbiota composition among children aged 3-5 years with varying body mass index(BMI)levels in Urumqi,and to provide a scientific basis for early microbiological warning and intervention strategies for childhood obesity.Methods A total of 40 children aged 3-5 years were enrolled.Based on their BMI percentiles,the participants were divided into 4 groups,including the underweight,normal weight,overweight,and obesity groups(n=10 per group).A total of 80 saliva and fecal samples were collected.Microbial community structures were analyzed using 16S rRNA gene sequencing,followed by bioinformatics and statistical analyses.Results Oral microbiota richness,as measured by Chao1 and observed-species indices,differed significantly among the four groups(P=0.004 7 and P=0.005 4,respectively),whereas no significant difference in gut microbiota diversity was observed(P>0.05).Beta diversity analysis revealed a distinct separation in oral microbiota between the normal-weight weight and other groups.At the genus level,obese children exhibited increased abundance in oral Leptotrichia,underweight children showed enrichment of gut Bacteroides,and overweight children showed increased abundance in gut Faecalibacterium and Blautia.Linear discriminant analysis effect size(LEfSe)analysis identified multiple biomarkers,including Prevotellaceae in the oral microbiota of normal-weight children,Catonella in the oral microbiota of obese children,and Clostridiales,Lachnospiraceae,and Hungatella in the gut microbiota of underweight children.Metabolic pathways related to lipopolysaccharide synthesis and amino acid metabolism were significantly upregulated in the microbiota of overweight and obese children.Conclusion Significant differences are observed in the oral and gut microbiota composition among children aged 3-5 years of different BMI levels in Urumqi.Oral microbiota show greater sensitivity to BMI changes.Specific genera,such as Catonella,Leptotrichia,and Prevotellaceae,may be involved in the development of obesity.The microbiota metabolic pathways in children with high BMI are characterized by the core features of inflammation activation and lipid metabolism dysregulation.
7.Relationship Between Single-Leg Standing Posture Control and Ankle Plantar Flexor Muscle Stability under Visual and Proprioceptive Interference
Chong WANG ; Mengyi WU ; Pengfei WANG ; Zeyu XING ; Hongfeng HUO
Journal of Medical Biomechanics 2025;40(5):1193-1199
Objective To explore the correlation between single-leg standing posture control and ankle plantar flexor muscle stability,so as to provide a new theoretical basis for improving the ability of human posture control.Methods A total of 20 healthy male college students were randomly selected as the experimental subjects.The iBalance tester and training system was used to test the trajectory data of the center of pressure(COP)of the foot standing on one leg.The CON-TREX MJ multi-joint isokinetic test and training system was used to test the moment amplitude data during the contraction of ankle plantar flexor muscles.Univariate repeated measures variance analysis was used to analyze the standard deviation data of ankle plantar flexor moment amplitude between groups.The Pearson correlation coefficient was used to study the correlation.Results The greater the intensity of the muscle stabilization task performed by the ankle plantar flexor muscle,the greater the standard deviation of the moment amplitude.The C90 area was positively correlated with the coefficient of variation(CV)of the 10%maximum voluntary contraction(MVC)moment of ankleplantar flexor muscle(r=0.761,P<0.05)during single-leg standing without interference.The C90 area was positively correlated with the CV(r=0.632,P<0.05)of the 30%MVC moment of ankle plantar flexor muscle during single-leg standing.When the proprioception was interfered during single-leg standing,the C90 area was positively correlated with the CV(r=0.583,P<0.05)of the 20%MVC moment amplitude of ankleplantar flexor muscle.Conclusions With the increasing difficulty of muscle strength stabilization performed by the ankle plantar flexor muscles,muscle stability decreases.There is a positive correlation between ankle plantar flexor strength stability and single-leg standing posture control.Compared with the case without interference,under visual and proprioceptive interference,an additional information input is reduced or disturbed,and it is more difficult to maintain body balance,and the ankle plantar flexor muscle needs a higher muscle stability in the force mode to participate in the posture control of the human body during single-leg standing.
8.Effect of dual tasks with different cognitive loads on prefrontal lobe activation and static posture control in young men
Mengyi WU ; Chong WANG ; Pengfei WANG ; Zeyu XING ; Hongfeng HUO
Chinese Journal of Rehabilitation Theory and Practice 2025;31(11):1322-1332
Objective To explore the effect of cognitive-motor dual tasks with different cognitive loads(none,simple and difficult)on activation of prefrontal cortex and static posture control in young man.Methods From June to July,2024,27 healthy male college students were recruited in Hebei Normal University.Static postural control parameters(C90 area),lower limb electromyography data(muscle energy proportion)and pre-frontal cortex hemodynamic signals of subjects under single task without cognitive load,dual-task with simple cognitive load,and dual-task with difficult cognitive load were collected using a balanced testing and training system,a wireless surface electromyography device,and functional near-infrared spectroscopy technology.Results The C90 areas of dual-tasks with simple and difficult cognitive load were smaller than that of the single task without cognitive load(P<0.05).The proportion of β band energy in the medial and lateral gastrocnemius mus-cles in the dual-task with simple cognitive load was greater than that in the single task without cognitive load(P<0.05),while the proportion of piper band energy in the lateral gastrocnemius muscle and tibialis anterior muscle was less(P<0.05).During dual-task with difficult cognitive load,the activation levels of bilateral ventro-lateral prefrontal cortex and right dorsolateral prefrontal cortex were higher than those in the single task without cognitive load(P<0.05).Conclusion Dual tasks with appopriate cognitive loads are effective on postural stability in young man.Simple cognitive load promote posture maintenance through optimizing the neuromuscular control of the lower limb muscle groups,while difficult cognitive load through activating the right prefrontal cortex involved in working memory and executive control,involving the neurocognitive compensatory.
9.Effect of dual tasks with different cognitive loads on prefrontal lobe activation and static posture control in young men
Mengyi WU ; Chong WANG ; Pengfei WANG ; Zeyu XING ; Hongfeng HUO
Chinese Journal of Rehabilitation Theory and Practice 2025;31(11):1322-1332
Objective To explore the effect of cognitive-motor dual tasks with different cognitive loads(none,simple and difficult)on activation of prefrontal cortex and static posture control in young man.Methods From June to July,2024,27 healthy male college students were recruited in Hebei Normal University.Static postural control parameters(C90 area),lower limb electromyography data(muscle energy proportion)and pre-frontal cortex hemodynamic signals of subjects under single task without cognitive load,dual-task with simple cognitive load,and dual-task with difficult cognitive load were collected using a balanced testing and training system,a wireless surface electromyography device,and functional near-infrared spectroscopy technology.Results The C90 areas of dual-tasks with simple and difficult cognitive load were smaller than that of the single task without cognitive load(P<0.05).The proportion of β band energy in the medial and lateral gastrocnemius mus-cles in the dual-task with simple cognitive load was greater than that in the single task without cognitive load(P<0.05),while the proportion of piper band energy in the lateral gastrocnemius muscle and tibialis anterior muscle was less(P<0.05).During dual-task with difficult cognitive load,the activation levels of bilateral ventro-lateral prefrontal cortex and right dorsolateral prefrontal cortex were higher than those in the single task without cognitive load(P<0.05).Conclusion Dual tasks with appopriate cognitive loads are effective on postural stability in young man.Simple cognitive load promote posture maintenance through optimizing the neuromuscular control of the lower limb muscle groups,while difficult cognitive load through activating the right prefrontal cortex involved in working memory and executive control,involving the neurocognitive compensatory.
10.Research and clinical application progress of foot lengthening surgery.
Zhiyu WANG ; Baozhou ZHANG ; Xuewen WANG ; Ban LU ; Zeyu ZHANG ; Yingdong ZHANG ; Sihe QIN ; Yong WU ; Hui DU
Chinese Journal of Reparative and Reconstructive Surgery 2025;39(8):937-941
OBJECTIVE:
To summarize the research and clinical application progress of foot lengthening surgery.
METHODS:
Relevant research literature on foot lengthening surgery in recent years at home and abroad was reviewed, and a summary was made from aspects such as the types of lengthening surgery, the types of foot diseases treated by clinical application, effectiveness, and complications.
RESULTS:
Bone defects and shortening deformities of the foot are relatively common clinically. As an innovative treatment method, foot lengthening surgery has gradually attracted attention, mainly including the Ilizarov technique and one-stage bone grafting lengthening surgery. The former promotes bone regeneration based on the tension-stress principle and is widely used in the treatment of calcaneal defects and congenital metatarsal brachymetatarsia, achieving good curative effects. However, there are also complications such as pin-tract infection, joint stiffness and contracture, non-union and delayed union of bone, re-fracture, and alignment deviation. The latter has a short treatment cycle, but the lengthening length is limited. Bone graft resorption and soft tissue complications are its main complications.
CONCLUSION
Foot lengthening surgery will develop towards the direction of personalization, intelligence, and precision. With the help of multi-center research, biological materials, and intelligent technologies, the effectiveness and safety will be further improved to better restore the function and appearance of the foot.
Humans
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Bone Transplantation/methods*
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Bone Lengthening/methods*
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Ilizarov Technique
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Osteogenesis, Distraction/methods*
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Foot Deformities/surgery*
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Postoperative Complications
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Treatment Outcome
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Foot/surgery*


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