1.Pseudolaric Acid B-linked Double-network Hydrogel Alleviates Pruritus by Inhibiting The Growth of Staphylococcus aureus
Ye YOU ; Yan YANG ; Tong-Yu LI ; Cheng-Long CAI ; Ting WANG ; Chan ZHU ; Zong-Xiang TANG
Progress in Biochemistry and Biophysics 2026;53(6):1734-1745
ObjectiveThis study aimed to elucidate the mechanistic role of Staphylococcus aureus in the pathogenesis of atopic dermatitis (AD), a chronic inflammatory skin disorder characterized by pruritus and barrier dysfunction. A key focus was screening traditional Chinese medicine (TCM) active components with dual antibacterial and antipruritic efficacy, followed by systematic evaluation of their in vitro antibacterial activity. Additionally, a novel drug delivery system was constructed to enable localized efficient drug delivery, inhibiting S. aureus proliferation and alleviating its induced pruritus, thereby providing new strategies for targeted AD therapy. MethodsMale C57BL/6J mice aged 6-8 weeks (body weight 18-22 g) were used to establish an AD model via repeated oxazolone sensitization. On day 14, microbial samples were collected from the lesional area (1 cm²) using sterile cotton swabs, followed by vortex mixing, serial dilution, and plating on 5% sheep blood agar plates (incubated at 37°C for 24 h). Single colonies with complete transparent β-hemolytic zones were isolated and identified as vancomycin-intermediate S. aureus (VISA) via 16S rRNA sequencing. An S. aureus mono-infection animal model was then established by applying gauze saturated with bacterial suspension (McFarland turbidity 0.1) to the nape and back skin of mice. The pruritic phenotype and inflammatory cell infiltration induced by S. aureus were evaluated using comprehensive approaches including behavioral assays (e.g., scratching frequency recording), hematoxylin-eosin (HE) staining, and toluidine blue staining. The in vitro antibacterial efficacy of the TCM monomer pseudolaric acid B (PAB) and double network hydrogel (DN) was separately assessed by disk diffusion assay, while the minimum inhibitory concentration (MIC) of PAB was determined via broth dilution method. Further validation of the pharmacodynamic characteristics of the composite system (PAB@DN, composed of PAB and DN) was conducted through behavioral assays, HE staining, and dermatitis scoring, with its drug release profile evaluated by mass spectrometry analysis. Based on scratching behavioral analysis and dermatitis scoring, the optimal ratio and concentration of PAB@DN were optimized. ResultsThe S. aureus load in AD lesional tissues was significantly higher than in normal skin ((5.3±0.33)×10⁶ CFU vs. (3.6±0.26)×10⁷ CFU, P<0.001). In the S. aureus mono-infection group, mice exhibited a 6.7-fold increase in scratching frequency compared to the control group. HE staining revealed marked epidermal thickening ((10.4±2.39) μm vs. (85.6±1.95) μm, P<0.000 1), and toluidine blue staining showed a 23-fold increase in mast cell degranulation. Pseudolaric acid B exhibited a significant concentration-dependent inhibitory effect onS. aureus growth, with its in vitro antibacterial effect being 57% that of the antibiotic cefepime (inhibition zone diameter: PAB (1.885±0.036) cm vs. cefepime (3.636±0.005) cm, P<0.000 1) and a minimum inhibitory concentration (MIC) of 1 g/L. The carrier double network hydrogel (DN) itself lacked direct antibacterial activity (no significant difference in inhibition zone diameter compared to the control) but effectively ameliorated the dry symptoms of AD-like lesions. The PAB@DN composite system demonstrated a synergistic effect compared to individual components, resulting in a 50% reduction in scratching behavior, an 86% decrease in dermatitis score, and a 60% reduction in epidermal thickening. It also reduced the S. aureus load in mouse skin by approximately 34%, with the optimal effective formulation being PAB at 1 g/L loaded onto DN. ConclusionS. aureus colonization plays a critical driving role in the onset and progression of AD. Using an S. aureus infection model, this study confirmed that the pseudolaric acidB-hydrogel composite delivery system (PAB@DN) can effectively alleviate S. aureus-induced pruritus and skin damage, providing experimental evidence for microbiota-targeted therapy of AD.
2.Preparation of sustained-release microspheres of ginsenosides
Xiang-ying LIU ; Ru-nan HE ; Gao QIU ; Zong-hao LIN ; Yu-hai GUO ; Chu-qin YU
Chinese Traditional Patent Medicine 2025;47(4):1097-1104
AIM To prepare the sustained-release microspheres of ginsenosides.METHODS The sustained-release microspheres were prepared by SPG membrane emulsification technology with poly(lactic-co-glycolic acid)(PLGA)as a shell carrier.With PLGA concentration,feed rate and Span 60 concentration as influencing factors,comprehensive score for appearance,drug loading and encapsulation efficiency as an evaluation indice,the preparation process was optimized by response surface method.The morphology of sustained-release microspheres was observed,after which the particle size,drug loading and encapsulation efficiency were determined,and the in vitro drug release was investigated.RESULTS The optimal conditons were determined to be 45 s for agitation time of primary emulsion,74.68 mg/mL for PLGA concentration,11%for feed rate,and 4.18 mg/mL for Span 60 concentration,the comprehensive score was 74.98.The round sustained-release microspheres demonstrated the average particle size of 4.33 μm,drug loading of(8.24±0.13)%,and encapsulation efficiency of(74.94±1.17)%,respectively.At 336 h,ginsenosides Rg1,Rb1,Rb2 displayed the accumulative release rates of 84.12%,78.04%,65.88%,respectively.CONCLUSION This reasonable and feasible method can be used for the preparation of sustained-release microspheres of ginsenosides with good appearance and high drug loading,which can provide references for the preparation of other water-soluble drug microspheres and solution of microsphere collapse problem.
3.Effects of a ferroptosis inhibitor on the apoptosis of photoreceptor cells and the Notch pathway in rats with retinal photochemical damage
Wenwen LI ; Hansheng WANG ; Shimiao ZONG ; Xiaoping YU
Recent Advances in Ophthalmology 2025;45(6):429-434
Objective To investigate the effects of the ferroptosis inhibitor Ferrostatin-1 on the apoptosis of photore-ceptor cells and the Notch pathway in rats with retinal photochemical damage(RPD).Methods Male Sprague-Dawley(SD)rats were randomly divided into the Control group(normally fed rats,intraperitoneal injection of an equal volume of saline),RPD group(RPD model rats,intraperitoneal injection of an equal volume of saline),Ferrostatin-1 group(RPD model rats,intraperitoneal injection of 5 mg·kg-1 Ferrostatin-1),and Ferrostatin-1+JFC group[RPD model rats,intrap-eritoneal injection of 5 mg·kg-1 Ferrostatin-1 and 0.5 mg·kg-1 Jagged1/FC chimeric protein(JFC,a Notch pathway acti-vator)],with 15 rats in each group.The retinal histopathology of rats in each group was evaluated via hematoxylin-eosin(HE)staining.The apoptosis of photoreceptor cells was detected by the terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assay.The expression level of ferrous ions(Fe2+),lactate dehydrogenase(LDH),malondialde-hyde(MDA),glutathione(GSH),and reactive oxygen species(ROS)in retinal tissues was measured using corresponding kits.Western blot was performed to assess the protein expression of transferrin receptor protein 1(TfR1),divalent metal transporter 1(DMT1),nuclear factor erythroid 2-related factor 2(Nrf2),solute carrier family 7 member 11(SLC7A11),recombinant glutathione peroxidase 4(GPX4),cleaved Caspase-3,Notch,and hairy and enhancer of split 1(Hes1).Results The thickness of the outer nuclear layer(ONL)in the Control group,RPD group,Ferrostatin-1 group,and Fer-rostatin-1+JFC group was(35.24±1.76)μm,(16.83±1.14)μm,(27.56±1.39)μm,and(21.48±1.23)μm,respec-tively;the apoptosis rate of photoreceptor cells in the four groups was(1.32±0.07)%,(18.57±1.63)%,(9.61±1.04)%,and(15.43±1.38)%,respectively.Compared with the Ferrostatin-1 group,the Ferrostatin-1+JFC group exhib-ited an aggravated retinal damage level,reduced ONL thickness,and increased apoptosis rate,and the differences were statistically significant(all P<0.05).The expression level of Fe2+,MDA,LDH,and ROS and the relative protein expres-sion level of TfR1,DMT1,cleaved Caspase-3,Notch,and Hes1 in the RPD group were higher than those in the Control group;while the expression level of GSH and the relative protein expression level of Nrf2,SLC7A11,and GPX4 were lower than those in the Control group,and the differences were statistically significant(all P<0.05).Compared with the RPD group,the Ferrostatin-1 group displayed a decrease in the expression level of Fe2+,MDA,LDH,and ROS and the relative protein expression level of TfR1,DMT1,cleaved Caspase-3,Notch,and Hes1 but an increase in the expression level of GSH and the relative protein expression level of Nrf2,SLC7A11,and GPX4,and the differences were statistically significant(all P<0.05).The expression level of Fe2+,MDA,LDH,and ROS and the relative protein expression level of TfR1,DMT1,cleaved Caspase-3,Notch,and Hes1 in the Ferrostatin-1+JFC group were higher than those in the Ferrostatin-1 group;while the expression level of GSH and the relative protein expression level of Nrf2,SLC7A11,and GPX4 were lower than those in the Ferrostatin-1 group,and the differences were statistically significant(all P<0.05).Conclusion Fer-rostatin-1 may alleviate retinal oxidative stress and the apoptosis of photoreceptor cells in RPD rats by inhibiting the Notch pathway,thereby mitigating retinal damage.
4.Effects of a ferroptosis inhibitor on the apoptosis of photoreceptor cells and the Notch pathway in rats with retinal photochemical damage
Wenwen LI ; Hansheng WANG ; Shimiao ZONG ; Xiaoping YU
Recent Advances in Ophthalmology 2025;45(6):429-434
Objective To investigate the effects of the ferroptosis inhibitor Ferrostatin-1 on the apoptosis of photore-ceptor cells and the Notch pathway in rats with retinal photochemical damage(RPD).Methods Male Sprague-Dawley(SD)rats were randomly divided into the Control group(normally fed rats,intraperitoneal injection of an equal volume of saline),RPD group(RPD model rats,intraperitoneal injection of an equal volume of saline),Ferrostatin-1 group(RPD model rats,intraperitoneal injection of 5 mg·kg-1 Ferrostatin-1),and Ferrostatin-1+JFC group[RPD model rats,intrap-eritoneal injection of 5 mg·kg-1 Ferrostatin-1 and 0.5 mg·kg-1 Jagged1/FC chimeric protein(JFC,a Notch pathway acti-vator)],with 15 rats in each group.The retinal histopathology of rats in each group was evaluated via hematoxylin-eosin(HE)staining.The apoptosis of photoreceptor cells was detected by the terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)assay.The expression level of ferrous ions(Fe2+),lactate dehydrogenase(LDH),malondialde-hyde(MDA),glutathione(GSH),and reactive oxygen species(ROS)in retinal tissues was measured using corresponding kits.Western blot was performed to assess the protein expression of transferrin receptor protein 1(TfR1),divalent metal transporter 1(DMT1),nuclear factor erythroid 2-related factor 2(Nrf2),solute carrier family 7 member 11(SLC7A11),recombinant glutathione peroxidase 4(GPX4),cleaved Caspase-3,Notch,and hairy and enhancer of split 1(Hes1).Results The thickness of the outer nuclear layer(ONL)in the Control group,RPD group,Ferrostatin-1 group,and Fer-rostatin-1+JFC group was(35.24±1.76)μm,(16.83±1.14)μm,(27.56±1.39)μm,and(21.48±1.23)μm,respec-tively;the apoptosis rate of photoreceptor cells in the four groups was(1.32±0.07)%,(18.57±1.63)%,(9.61±1.04)%,and(15.43±1.38)%,respectively.Compared with the Ferrostatin-1 group,the Ferrostatin-1+JFC group exhib-ited an aggravated retinal damage level,reduced ONL thickness,and increased apoptosis rate,and the differences were statistically significant(all P<0.05).The expression level of Fe2+,MDA,LDH,and ROS and the relative protein expres-sion level of TfR1,DMT1,cleaved Caspase-3,Notch,and Hes1 in the RPD group were higher than those in the Control group;while the expression level of GSH and the relative protein expression level of Nrf2,SLC7A11,and GPX4 were lower than those in the Control group,and the differences were statistically significant(all P<0.05).Compared with the RPD group,the Ferrostatin-1 group displayed a decrease in the expression level of Fe2+,MDA,LDH,and ROS and the relative protein expression level of TfR1,DMT1,cleaved Caspase-3,Notch,and Hes1 but an increase in the expression level of GSH and the relative protein expression level of Nrf2,SLC7A11,and GPX4,and the differences were statistically significant(all P<0.05).The expression level of Fe2+,MDA,LDH,and ROS and the relative protein expression level of TfR1,DMT1,cleaved Caspase-3,Notch,and Hes1 in the Ferrostatin-1+JFC group were higher than those in the Ferrostatin-1 group;while the expression level of GSH and the relative protein expression level of Nrf2,SLC7A11,and GPX4 were lower than those in the Ferrostatin-1 group,and the differences were statistically significant(all P<0.05).Conclusion Fer-rostatin-1 may alleviate retinal oxidative stress and the apoptosis of photoreceptor cells in RPD rats by inhibiting the Notch pathway,thereby mitigating retinal damage.
5.Clinical effect of drug-coated balloon combined with drug eluting stent on coronary bifurcation le-sions
Zong-yu XU ; Xiao-ming WANG ; Zhou-tong LI ; Yi-wei CHEN ; Jin-quan JIANG
Chinese Journal of cardiovascular Rehabilitation Medicine 2025;34(4):487-492
Objective:To explore the therapeutic effect of drug-coated balloon(DCB)combined drug-eluting stent(DES)on coronary bifurcation lesions.Methods:A total of 108 patients with coronary bifurcation lesions admitted in Shanghai Ninth People's Hospital Huangpu Branch,Shanghai Jiaotong University School of Medicine between February 2021 and March 2023 were enrolled in this randomized controlled study.Patients were randomly divided into combined treatment group(n=54,DCB was implanted in the sub-branch,and DES was implanted in the main branch)and DES group(n=54,DES were implanted in both main branch and sub-branch).Clinical therapeutic effect,coronary angiography quantitative parameters before,instant and 9 months after operation and clinical out-comes during 1-year follow-up after operation were compared between two groups.Results:The total effective rate of combined treatment group was significantly higher than that of DES group(96.30%vs.87.04%,P=0.030).Compared to those in DES group,instant and 9 months after operation,patients in the combined treatment group had significant higher diameters of main branch vessel[(3.13±0.31)mm vs.(3.01±0.25)mm,(2.99±0.33)mm vs.(2.84±0.23)mm],sub-branch vessel[(2.51±0.26)mm vs.(2.42±0.13)mm,(2.44±0.24)mm vs.(2.29±0.36)mm],and significant lower main branch stenosis rate[(6.05±0.21)%vs.(6.24±0.31)%,(9.06±0.23)%vs.(10.12±0.12)%]and sub-branch stenosis rate[(7.38±0.42)%vs.(7.63±0.18)%,(8.07±0.39)%vs.(11.25±0.22)%](P<0.05 or<0.01).There were no significant difference in incidence of target lesion revascularization,cardiogenic death and major adverse cardiovascular events between two groups(P>0.05 all).Conclusion:Drug-eluting stent combined drug-coated balloon may promote vascular branch dilation of coro-nary artery lesions,increase the minimum lumen diameter of sub-branch vessels,and reduce the occurrence of ste-nosis in the treatment of coronary bifurcation lesion,which had similar effectiveness and safety with drug-eluting stent technique.
6.Clinical effect of drug-coated balloon combined with drug eluting stent on coronary bifurcation le-sions
Zong-yu XU ; Xiao-ming WANG ; Zhou-tong LI ; Yi-wei CHEN ; Jin-quan JIANG
Chinese Journal of cardiovascular Rehabilitation Medicine 2025;34(4):487-492
Objective:To explore the therapeutic effect of drug-coated balloon(DCB)combined drug-eluting stent(DES)on coronary bifurcation lesions.Methods:A total of 108 patients with coronary bifurcation lesions admitted in Shanghai Ninth People's Hospital Huangpu Branch,Shanghai Jiaotong University School of Medicine between February 2021 and March 2023 were enrolled in this randomized controlled study.Patients were randomly divided into combined treatment group(n=54,DCB was implanted in the sub-branch,and DES was implanted in the main branch)and DES group(n=54,DES were implanted in both main branch and sub-branch).Clinical therapeutic effect,coronary angiography quantitative parameters before,instant and 9 months after operation and clinical out-comes during 1-year follow-up after operation were compared between two groups.Results:The total effective rate of combined treatment group was significantly higher than that of DES group(96.30%vs.87.04%,P=0.030).Compared to those in DES group,instant and 9 months after operation,patients in the combined treatment group had significant higher diameters of main branch vessel[(3.13±0.31)mm vs.(3.01±0.25)mm,(2.99±0.33)mm vs.(2.84±0.23)mm],sub-branch vessel[(2.51±0.26)mm vs.(2.42±0.13)mm,(2.44±0.24)mm vs.(2.29±0.36)mm],and significant lower main branch stenosis rate[(6.05±0.21)%vs.(6.24±0.31)%,(9.06±0.23)%vs.(10.12±0.12)%]and sub-branch stenosis rate[(7.38±0.42)%vs.(7.63±0.18)%,(8.07±0.39)%vs.(11.25±0.22)%](P<0.05 or<0.01).There were no significant difference in incidence of target lesion revascularization,cardiogenic death and major adverse cardiovascular events between two groups(P>0.05 all).Conclusion:Drug-eluting stent combined drug-coated balloon may promote vascular branch dilation of coro-nary artery lesions,increase the minimum lumen diameter of sub-branch vessels,and reduce the occurrence of ste-nosis in the treatment of coronary bifurcation lesion,which had similar effectiveness and safety with drug-eluting stent technique.
7.RCM method-based study on preventive maintenance strategy of heating,ventilation and air-conditioning system in pharmacy intravenous admixture services
Liu-liu ZONG ; Yun-zhi YANG ; Jing ZHAO ; Yun MO ; Dong-hui LAO ; Jian-zhong ZHANG ; Xiao-yu LI ; Qian-zhou LYU
Chinese Medical Equipment Journal 2025;46(10):78-83
Objective To propose a preventive maintenance strategy of the heating,ventilation and air-conditioning(HVAC)system in pharmacy intravenous admixture services(PIVAS)based on the reliability centered maintenance(RCM)method so as to provide references for PIVAS equipment maintenance.Methods Firstly,a HVAC system RCM review team was formed,and the failure modes and impacts of important functional components of the equipment were analyzed to clarify the consequences of the failure of each functional component under the premise of ensuring the safety and integrity of the equipment and with the goal of minimizing the loss of maintenance downtime and the consumption of maintenance resources.Secondly,with a standardized logical decision-making procedure the preventive maintenance strategy was determined and implemented based on the consequences of functional failure.Finally,statistical analyses were carried out on such equipment indicators as performance parameter qualification rate,failure rate and maintenance cost before and after the RCM method-based strategy was executed,in order to evaluate the efficacy of the strategy.Results The RCM method-based preventive maintenance strategy had the performance qualification rate increased from 97.47%to 99.06%(χ2=24.139,P<0.01),the failure rate decreased from 0.24%to 0.03%(χ2=13.519,P<0.01)and the maintenance cost reduced by 11.5%,from RMB 134,200 to 118,700.Conclusion The RCM method-based preventive maintenance strategy provides reliable equipment for PIVAS and lowers the maintenance cost effectively,and references are given for the development of automated and intelligent equipment maintenance strategies for PIVAS.[Chinese Medical Equipment Journal,2025,46(10):78-83]
8.RCM method-based study on preventive maintenance strategy of heating,ventilation and air-conditioning system in pharmacy intravenous admixture services
Liu-liu ZONG ; Yun-zhi YANG ; Jing ZHAO ; Yun MO ; Dong-hui LAO ; Jian-zhong ZHANG ; Xiao-yu LI ; Qian-zhou LYU
Chinese Medical Equipment Journal 2025;46(10):78-83
Objective To propose a preventive maintenance strategy of the heating,ventilation and air-conditioning(HVAC)system in pharmacy intravenous admixture services(PIVAS)based on the reliability centered maintenance(RCM)method so as to provide references for PIVAS equipment maintenance.Methods Firstly,a HVAC system RCM review team was formed,and the failure modes and impacts of important functional components of the equipment were analyzed to clarify the consequences of the failure of each functional component under the premise of ensuring the safety and integrity of the equipment and with the goal of minimizing the loss of maintenance downtime and the consumption of maintenance resources.Secondly,with a standardized logical decision-making procedure the preventive maintenance strategy was determined and implemented based on the consequences of functional failure.Finally,statistical analyses were carried out on such equipment indicators as performance parameter qualification rate,failure rate and maintenance cost before and after the RCM method-based strategy was executed,in order to evaluate the efficacy of the strategy.Results The RCM method-based preventive maintenance strategy had the performance qualification rate increased from 97.47%to 99.06%(χ2=24.139,P<0.01),the failure rate decreased from 0.24%to 0.03%(χ2=13.519,P<0.01)and the maintenance cost reduced by 11.5%,from RMB 134,200 to 118,700.Conclusion The RCM method-based preventive maintenance strategy provides reliable equipment for PIVAS and lowers the maintenance cost effectively,and references are given for the development of automated and intelligent equipment maintenance strategies for PIVAS.[Chinese Medical Equipment Journal,2025,46(10):78-83]
9.In vitro fluorescent substrate assay for the activity of leucine aminopeptidase(LAP)in Echinococcus multilocularis
Jia-yu CHEN ; Yao DAI ; Shun-juan WANG ; Yang XIAO ; Xin-zong YAN ; Tong LIU ; Zhi-hao YUAN ; Kai-li SHI ; Run-le LI ; Feng TANG
Chinese Journal of Zoonoses 2025;41(1):23-31
This study was aimed at developing an in vitro fluorescent substrate assay for the activity of leucyl aminopeptid-ase(LAP)from Echinococcus multilocularis and comparing it with the chemical chromogenic substrate enzyme activity assay.Through the establishment of reaction conditions for the fluorescent substrate-based in vitro enzyme activity assay,we com-pared the differences between the fluorescent substrate L-Leucine-7-amido-4-methylocoumarin(Leu-AMC)and the chemical chromogenic substrate L-Leucine-4-nitroanilide(Leu-pNA)through molecular docking,inhibition rates,and precision measures.Molecular docking revealed that the fluorescent substrate Leu-AMC had higher affinity for the protein than the chemical chromogenic substrate Leu-pNA.Through analysis of the effects of varying reaction conditions on fluorescence intensi-ty,we optimized the fluorescent substrate enzyme activity assay to demonstrate favorable performance at a reaction temperature of 37℃,a pH of 9.0,a protein concentration of 800 nmol/L,and a reaction duration of 60 minutes.Leu-AMC exhibited significant and distinct responses at a 5 μmol/L substrate concentration,under varying substrate conditions.The fluo-rescent substrate assay demonstrated more significant intergroup differences than the chemical chromogenic substrate assay when various inhibitors were added.This study established a fluorescence-based enzyme activity assay for leucyl aminopeptidase from Echinococcus multilocularis by using Leu-AMC as the substrate;this method demonstrated a more significant intergroup difference and sensitivity than the chemical chromogenic substrate assay.
10.Progress of research on epidemiology and drug resistance mechanism of Elizabethkingia anopheles infection
Jie SUN ; Yulong ZONG ; Yongpeng SHANG ; Shanshan WANG ; Fangyou YU
Chinese Journal of Nosocomiology 2025;35(20):3188-3193
In recent years the detection rate of Elizabethkingia anopheles(EA)in China has shown an upward trend,making it one of the important pathogens causing hospital and community infections.EA accounts for 59.3%to 96.2%of the Elizabethkingia species,and can cause meningitis,pneumonia,bacteremia,etc.There are limited researches on its pathogenic mechanism,which mainly involves various virulence factors.EA is a mul-tidrug-resistant bacterium,with drug resistance mechanisms including biofilm formation,efflux pumps and carry-ing multiple resistance genes(such as GOB,BlaB).Currently,minocycline,piperacillin/tazobactam,trime-thoprim/sulfamethoxazole and rifampin are effective drugs for treating EA infections.Clinically,efforts are be-ing made to find the optimal antibacterial drug combination to achieve ideal therapeutic effects.This paper reviews the epidemiological characteristics,pathogenic mechanisms,drug resistance mechanisms and treatment options of EA,aiming to provide a reference for clinical prevention,control,diagnosis and treatment of EA infections.

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