1.Cross-sectional survey of healthcare-associated infection in 5 736 medical institutions across China in 2024
Cui ZENG ; Wuqiang GAO ; Fu QIAO ; Hui ZHAO ; Xu FANG ; Linping LI ; Xiuwen CHEN ; Jiansen CHEN ; Dan LI ; Yuan ZHOU ; Lingli YU ; Qinglan MENG ; Xia MOU ; Lijuan XIONG ; Weiguang LI ; Ding LIU ; Jiaqing XIAO ; Limei OU ; Baozhen LI ; Jun YIN ; Haojun ZHANG ; Qiang FU ; Qun LU ; Biao WU ; Ya-wei XING ; Shumei SUN ; Shuncai WANG ; Longmin DU ; Jingping ZHANG ; Wen-ying HE ; Gui CHENG ; Nan REN ; Xun HUANG ; Anhua WU
Chinese Journal of Infection Control 2025;24(11):1572-1583
Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27%.The number of HAI episodes was 38 032,and case prevalence rate was 1.38%.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66%to 2.35%.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65%.The most common infection site was the lower respiratory tract(44.66%),followed by the urinary tract(12.94%),surgical site(9.32%),upper respiratory tract(7.02%),and bloodstream infection(5.78%).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02%),department of neurosurgery(5.51%),and department(group)of hematology(5.34%).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10%)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76%),Pseudomonas aeruginosa(13.33%),Escherichia coli(12.79%),Acinetobacter baumannii(9.23%),and Staphylococcus aureus(7.88%).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71%.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18%.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46%.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.
2.An investigation into how fixation and permeabilization affect antigens'mean fluorescence values and percentage of positive cells obtained through flow cytometry
Xianing GUO ; Yuxin LIU ; Song YU ; Rong LI ; Ye YANG ; Jiaqing LI ; Meng CAO ; Jing LUAN
Chinese Journal of Immunology 2025;41(8):1997-2002
Objective:Conventional myeloid cell staining methodologies were employed to stain splenocytes and peripheral blood cells by fixation and permeabilization and non-fixation and permeabilization methods,respectively,and effects of staining were compared following flow cytometry detection.Methods:Peripheral blood and spleen of three 8-week-old C57 male mice were divided into fixation and permeabilization group and non-fixation and permeabilization group for staining,and flow cytometry was used to detect mean fluorescence intensity(MFI)of each fluorescent antibody and proportion of positive cells.Results:In mouse peripheral blood samples,MFI of 7-AAD-PerCP-Cyanine5.5 and CD147-PE were lower in fixation and permeabilization group than non-fixation and permeabilization group,MFI of F4/80-FITC,MHC Class Ⅱ(I-A/I-E)-APC-R700,Ly-6c-APC-Cy7,CD206-BV421,CD45-BV510,CD11b-BV605,CD11c-BV650 and CD86-BV786 were higher than non-fixation and permeabilization group.Proportions of each immune cell in fixation and permeabilization group and non-fixation and permeabilization group were highly similar.In mouse spleen samples,MFI of antibodies in fixation and permeabilization group were higher than those in non-fixation and permeabilization group,with exception of CD147-PE,which had a lower MFI than non-fixation and permeabilization group;proportions of dendritic cells and Mon/Ly-6clow cells were lower than non-fixation and permeabilization group,whereas proportions of rest myeloid subpopula-tions were higher than non-fixation and permeabilization group.Conclusion:Fixation and permeabilization in peripheral blood cells can improve antibody MFI,but it has little effect on proportion of positive cells.Fixation and permeabilization can enhance antibody MFI in splenocytes,while effect on proportion of each positive cell is more significant.It is advised that when designing staining strate-gies,researchers attempt to choose alternative cell surface antigens for assay or optimize protocols through required pre-experiments in order to acquire stable and dependable results.
3.Cross-sectional survey of healthcare-associated infection in 5 736 medical institutions across China in 2024
Cui ZENG ; Wuqiang GAO ; Fu QIAO ; Hui ZHAO ; Xu FANG ; Linping LI ; Xiuwen CHEN ; Jiansen CHEN ; Dan LI ; Yuan ZHOU ; Lingli YU ; Qinglan MENG ; Xia MOU ; Lijuan XIONG ; Weiguang LI ; Ding LIU ; Jiaqing XIAO ; Limei OU ; Baozhen LI ; Jun YIN ; Haojun ZHANG ; Qiang FU ; Qun LU ; Biao WU ; Ya-wei XING ; Shumei SUN ; Shuncai WANG ; Longmin DU ; Jingping ZHANG ; Wen-ying HE ; Gui CHENG ; Nan REN ; Xun HUANG ; Anhua WU
Chinese Journal of Infection Control 2025;24(11):1572-1583
Objective To understand the current situation of healthcare-associated infection(HAI)in China,pro-vide data support and decision-making basis for formulating scientific and effective strategies for HAI prevention and control.Methods A nationwide cross-sectional survey on HAI was conducted among various types and levels of medical institutions in China according to a unified protocol of bedside surveys and case investigations.Results In 2024,a total of 5 736 medical institutions and 2 751 765 patients were surveyed.Among them,34 889 HAI cases were identified,with a prevalence rate of 1.27%.The number of HAI episodes was 38 032,and case prevalence rate was 1.38%.The prevalence rate of HAI in medical institutions in different regions of China ranged from 0.66%to 2.35%.Among medical institutions of different scales,those with a bed capacity of ≥900 had the high-est incidence of HAI,reaching 1.65%.The most common infection site was the lower respiratory tract(44.66%),followed by the urinary tract(12.94%),surgical site(9.32%),upper respiratory tract(7.02%),and bloodstream infection(5.78%).The top 3 departments with the highest HAI rates were the general intensive care unit(10.02%),department of neurosurgery(5.51%),and department(group)of hematology(5.34%).A total of 23 238 strains of HAI pathogens were detected,with 10 714 strains(46.10%)from lower respiratory tract speci-mens.The top 5 detected strains were Klebsiella pneumoniae(14.76%),Pseudomonas aeruginosa(13.33%),Escherichia coli(12.79%),Acinetobacter baumannii(9.23%),and Staphylococcus aureus(7.88%).231 944 pa-tients underwent class Ⅰ incision surgery were monitored,with 1 647 cases experienced surgical site infection,and the prevalence rate of surgical site infection was 0.71%.The number of patients who should undergo pathogen de-tection(patients receiving therapeutic and therapeutic combined prophylactic antimicrobial agents)was 715 179,while the actual number was 480 492,with a pathogen detection rate of 67.18%.425 225 patients received patho-genic detection before treatment,with a detection rate of 59.46%.Conclusion The overall HAI prevalence in Chi-na is lower,showing disparities among medical institutions of different regions and scales.Therefore,precise imple-mentation of measures is necessary for HAI prevention and control,with a focus on high-risk institutions and high-risk departments,key areas,and critical procedures.All levels of medical institutions should continuously reduce the incidence of HAI by strengthening monitoring,standardizing the use of antimicrobial agents,and reinforcing basic HAI prevention and control measures.
4.An investigation into how fixation and permeabilization affect antigens'mean fluorescence values and percentage of positive cells obtained through flow cytometry
Xianing GUO ; Yuxin LIU ; Song YU ; Rong LI ; Ye YANG ; Jiaqing LI ; Meng CAO ; Jing LUAN
Chinese Journal of Immunology 2025;41(8):1997-2002
Objective:Conventional myeloid cell staining methodologies were employed to stain splenocytes and peripheral blood cells by fixation and permeabilization and non-fixation and permeabilization methods,respectively,and effects of staining were compared following flow cytometry detection.Methods:Peripheral blood and spleen of three 8-week-old C57 male mice were divided into fixation and permeabilization group and non-fixation and permeabilization group for staining,and flow cytometry was used to detect mean fluorescence intensity(MFI)of each fluorescent antibody and proportion of positive cells.Results:In mouse peripheral blood samples,MFI of 7-AAD-PerCP-Cyanine5.5 and CD147-PE were lower in fixation and permeabilization group than non-fixation and permeabilization group,MFI of F4/80-FITC,MHC Class Ⅱ(I-A/I-E)-APC-R700,Ly-6c-APC-Cy7,CD206-BV421,CD45-BV510,CD11b-BV605,CD11c-BV650 and CD86-BV786 were higher than non-fixation and permeabilization group.Proportions of each immune cell in fixation and permeabilization group and non-fixation and permeabilization group were highly similar.In mouse spleen samples,MFI of antibodies in fixation and permeabilization group were higher than those in non-fixation and permeabilization group,with exception of CD147-PE,which had a lower MFI than non-fixation and permeabilization group;proportions of dendritic cells and Mon/Ly-6clow cells were lower than non-fixation and permeabilization group,whereas proportions of rest myeloid subpopula-tions were higher than non-fixation and permeabilization group.Conclusion:Fixation and permeabilization in peripheral blood cells can improve antibody MFI,but it has little effect on proportion of positive cells.Fixation and permeabilization can enhance antibody MFI in splenocytes,while effect on proportion of each positive cell is more significant.It is advised that when designing staining strate-gies,researchers attempt to choose alternative cell surface antigens for assay or optimize protocols through required pre-experiments in order to acquire stable and dependable results.
5.Progress in animal models of hemophilic arthritis
Kun LIN ; Xianshun HE ; Jiaqing TIAN ; Shun LU ; Mincong HE ; Tianye LIN ; Xiaoming HE ; Shuai FAN ; Hongguang YANG ; Tianqi YU ; Daguang ZHANG ; Wei HE ; Qiushi WEI
Acta Laboratorium Animalis Scientia Sinica 2024;32(4):523-529
Hemophilic arthritis(HA),caused by recurrent bleeding,can seriously affect patient quality of life and consumes extensive social and medical resources.There is thus a need to establish an animal model of HA for research;however,this is limited by ethical requirements.Here we review the recent literature and summarize research progress into animal models of HA at home and abroad,from the aspects of species selection,modeling method,histopathology,and imaging evaluation method.Species selection includes rodents such as mice,New Zealand rabbits,beagles,miniature pigs,and crab-eating macaques.Modeling method comprise gene knockout trauma models,gene knockout spontaneous models,and injection models.Among these,the gene knockout spontaneous model closely mimics the pathological process of spontaneous bleeding and concurrent arthritis in human HA,making it more relevant to human HA.However,due to high modeling costs,phenotypic instability,and low survival rates,this model is not the preferred choice for animal experimental studies.In contrast,gene knockout trauma models exhibit characteristics such as short modeling time,strong stability,and high success rates,thus being widely utilized in animal experimental research.Evaluation of HA models involves various imaging method including MRI,micro-CT,MSKUS/PD,in addition to various gross scoring method.By reviewing the progress of HA model research,more experimental evidence is provided for investigating the pathogenesis and validating the efficacy of HA treatments,thereby compensating for the lack of clinical data,particularly in the field of traditional Chinese medicine therapy.
6.Relationship between the lowest hemoglobin value during hospitalization and the prognosis in patients with extensive burns
Fangqing ZUO ; Jiaqing SU ; Yang LI ; Lijuan ZHANG ; Yingying LAN ; Yu CHEN ; Yali GONG ; Yajie CHEN ; Junda LI ; Yizhi PENG ; Gaoxing LUO ; Zhiqiang YUAN
Chinese Journal of Burns 2024;40(6):543-550
Objective:To investigate the relationship between the lowest hemoglobin value during hospitalization and the prognosis in patients with extensive burns, in order to explore the hemoglobin warning threshold for blood transfusion in patients with extensive burns.Methods:The research was a retrospective observational study. From October 2012 to October 2022, 288 patients with extensive burns who met the inclusion criteria were admitted to the First Affiliated Hospital of Army Medical University (the Third Military Medical University), including 243 males and 45 females, aged 18 to 65 years. These patients were assigned to the death group ( n=54) and the survival group ( n=234) based on their final prognosis. The clinical data including gender, age, body mass index, total burn area, full-thickness burn area, time of first operation after injury, preoperative prothrombin time (PT) and activated partial thromboplastin time (APTT) and hemoglobin level of the first surgery, complication of inhalation injury, number of surgeries, total surgical area, total surgical time, total length of hospital stay, and highest procalcitonin value, lowest platelet count and hemoglobin values, and occurrence of sepsis during hospitalization were compared between the two groups of patients. According to the lowest hemoglobin value during hospitalization, the patients were assigned to <65 g/L group, ≥65 g/L and <75 g/L group, ≥75 g/L and <85 g/L group, and ≥85 g/L group. The total length of hospital stay, mortality and incidence of sepsis during hospitalization, and mortality within 90 days after injury were compared among the four groups of patients. The relationship between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns was analyzed using a restricted cubic spline model before and after adjusting covariates. A logistic regression model was adopted to analyze the relationship between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns after adjusting covariates, with the lowest hemoglobin value during hospitalization as a continuous variable and a categorical variable, separately. Results:Compared with those in survival group, the total burn area, full-thickness burn area, and total surgical area of patients in death group were significantly increased, the preoperative APTT of the first surgery was significantly prolonged, the number of surgeries was significantly reduced, the total length of hospital stay was significantly shortened, the highest procalcitonin value during hospitalization was significantly increased, the lowest platelet count and hemoglobin values during hospitalization were significantly decreased, and the incidence proportion of sepsis during hospitalization was significantly increased (with Z values of -6.72, -5.40, -2.15, -2.99, -2.21, -7.84, -6.23, -7.03, and -3.43, respectively, χ2=161.95, P values all <0.05). There were no statistically significant differences in the other clinical data of patients between the two groups ( P>0.05). There were statistically significant differences in mortality and incidence of sepsis during hospitalization, and mortality within 90 days after injury of patients among the four groups divided according to the lowest hemoglobin value during hospitalization (with χ2 values of 12.12, 15.93, and 10.62, respectively, P<0.05). There was no statistically significant difference in the total length of hospital stay of patients among the four groups ( P>0.05). The restricted cubic spline model analysis revealed an approximately linear relationship between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns before and after adjusting covariates (with χ2 values of 0.81 and 0.75, respectively, P>0.05). After adjusting covariates, the logistic regression model analysis showed that the mortality risk of patients with extensive burns increased with decreasing hemoglobin when the lowest hemoglobin value during hospitalization was analyzed as a continuous variable (with odds ratio of 0.96, with 95% confidence interval of 0.92 to 0.99, P<0.05). When using the median value of 75.5 g/L as the cut-off value for categorizing the lowest hemoglobin value during hospitalization, there was no statistically significant difference in the mortality risk between patients with hemoglobin <75.5 g/L and those with hemoglobin ≥75.5 g/L ( P>0.05). When the patients were divided into four groups based on the lowest hemoglobin value during hospitalization as above, using ≥85 g/L group as a reference, only patients in <65 g/L group had a significantly increased mortality risk (with odds ratio of 5.37, with 95% confidence interval of 1.57 to 18.29, P<0.05). Conclusions:There is an approximately linear correlation between the lowest hemoglobin value during hospitalization and the mortality risk of patients with extensive burns. When the hemoglobin level drops to 65 g/L or lower, the mortality risk of patients increases significantly, suggesting that a hemoglobin level of 65 g/L could serve as a warning threshold for blood transfusion in patients with extensive burns.
7.Issues in centralized procurement with volume of medical consumables in public hospitals
Lihua WU ; Jiaqing MIAO ; Siwei DU ; Jiawen TAN ; Zhilun YANG ; Donglan YU ; Qingtang ZHU
Modern Hospital 2024;24(5):757-761
Objective In the context of expanding in size and improving the quality of medical consumables,the"one product,one policy"approach has brought challenges to the management of consumables in public hospitals.This study investi-gated the potential management problems in the process of centralized procurement with volume of medical consumables in a pub-lic tertiary hospital in Guangdong Province,and accordingly worked out the corresponding management countermeasures and then assessed their implementation effects.Methods The fishbone diagrams was applied to systematically analyze the potential prob-lems in the implementation process of centralized procurement with volume of medical consumables.Targeted measures were worked out from May to July 2023 in the hospital.The time series data of centralized procurement of coronary stents,pacemak-ers,tubular/end-to-end anastomoses,and spinal products from December 2022 to December 2023 were analyzed.Changes in the monthly implementation rate and contract completion volume pre-and post-intervention were measured to evaluate the effectiveness of the intervention.Results The fishbone diagrams analysis revealed that the primary factors impeding procurement implementa-tion were internal system flaws,personnel management inadequacy,supply issues,and an absence of an information system.Post-intervention,the monthly implementation rate(t=-4.19,P<0.05)and contract completion(t=-2.38,P<0.05)significantly improved.Conclusion The implementation of intervention management for centralized procurement with volume of medical consumables can effectively promote the related implementation effect in the department.In the context of centralized pro-curement,clinical and health management personnel need to bolster their professionalism to ensure the procurement management efficiency and quality.It is crucial to deepen policy understanding and implementation,enhance production and distribution process supervision and disciplinary mechanisms,ensure multi-departmental coordination for supply security,and improve hospi-tal information systems and procurement platforms.
8.Cost control and structural optimization of medical consumables in a public hospital:a case study on the management of drug-loaded embolic microspheres in transcatheter Hepatic Artery Embolization
Jiawen TAN ; Zhilun YANG ; Jiaqing MIAO ; Xiaohui LV ; Lihua WU ; Donglan YU
Modern Hospital 2024;24(11):1694-1698,1701
Effective cost control and structure optimization of medical consumables in public hospitals can facilitate a shift from extensive cost control to scientific and refine management.On the premise of ensuring medical quality,reducing the burden of patients'diagnosis and treatment and meeting the actual needs of hospital management,this approach aims to realize valuable healthcare outcomes.This study was conducted in a tertiary hospital,which balanced both the medical and economic val-ue of medical consumables.Using an integrated approach to specialty capacity building and disease structure optimization,the hospital restructured the use of medical consumables in Transcatheter Arterial Embolization(TAE)procedures.It developed standardized pathways and usage protocols tailored to specific diseases and surgical requirements.A targeted consumable usage policy framework was introduced,comprising"one department,one policy;one surgery type,one policy;and one consumable,one policy."This included initiatives such as validating the use of drug-loaded embolic microspheres,conducting multi-depart-mental review meetings,strictly regulating indications for these microspheres,limiting personnel involvement,and negotiating re-duced pricing on imported microspheres.Following implementation,the average case-mix index(CMI)for discharged patients undergoing TAE increased from 2.23 to 2.34(P<0.001),while the average per-case cost of consumables decreased from 19 600 to 15 600(P<0.001).These measures offer valuable decision-making and operational reference for hospitals nation-wide,supporting efficient,quality-focused consumables management.
9.Changes in the subfoveal choroidal thickness of children and adolescents with different refractive states
Jinling ZHANG ; Yujie LIAO ; Xiaoyan YU ; Qi YANG ; Jiaqing KANG ; Jiawen LU ; Chen CHEN ; Haohao ZHU
Recent Advances in Ophthalmology 2024;44(11):883-886
Objective To observe the changes in the subfoveal choroidal thickness(SFCT)of children and adoles-cents with different refractive states using optical coherence tomography angiography.Methods A total of 171 children and adolescents were followed.They were divided into the lower primary school group(6-8 years old),upper primary school group(9-11 years old),and junior high school group(12-14 years old)according to their age at the time of en-rollment.Dioptric examinations(including best corrected visual acuity,diopter,intraocular pressure,corneal curvature,axial length and SFCT)were performed,data collection was conducted twice in half a year(initial examination and review after half a year),and the eyeball parameters and changes in eyeball parameters after half a year among all groups were compared.Results The axial length and SFCT of subjects had significant differences among all groups(both P<0.05).In children and adolescents,the axial length gradually lengthened and SFCT gradually thickened with age,while intraocular pressure and corneal curvature were not associated with age(both P>0.05).In the initial examination and review after half a year,there was no significant difference in intraocular pressure,corneal curvature and SFCT of subjects with differ-ent refractive states in all groups(all P>0.05),while the axial length of myopic subjects was greater than that of non-my-opic subjects in all groups(all P<0.05).In the review after half a year,the SFCT of non-myopic subjects in the lower pri-mary school group and upper primary school group was significantly thickened(P<0.001,P=0.003),while there was no significant difference in SFCT of myopic subjects in all groups compared with the value half a year ago(all P>0.05).The axial length of all subjects showed a positive correlation with the SFCT in the initial examination and review after half a year(r=0.354,0.228,P<0.05).Conclusion Myopia affects the increase in SFCT in children and adolescents.
10.The clinical value of MHR in chronic heart failure with dilated cardiomyopathy
Jiaqing Yu ; Min Han ; Bing Zhu ; Yitong Ma
Acta Universitatis Medicinalis Anhui 2022;57(12):1997-2001,2006
Objective :
To explore the clinical value of monocyte count and high-density lipoprotein cholesterol ratio (MHR) in the diagnosis and treatment of chronic heart failure in patients with dilated cardiomyopathy ( DCM) .
Methods :
A total of hosphospitalized 300 patients with chronic heart failure in DCM was selected and divided into NYHA Ⅱ , NYHA Ⅲ and NYHA Ⅳ group ( 100 patients) ,according to the cardiac function classification of New York Heart Association (NYHA) .In the same period,100 patients with organic heart disease and chronic heart failure were selected as the control group.The level of MHR , the relationship between MHR and N-terminal precur- sor B-type natriuretic peptide ( NT-pro BNP) ,and the relationship between MHR and echocardiographic indexes related to cardiac remodeling and cardiac function were observed and analyzed in DCM patients with chronic heart failure .
Results :
The MHR of DCM patients with chronic heart failure was significantly higher than that of the con- trol group (P<0. 001) ,and there were differences among different grades of heart failure in the case group (P < 0. 05) .After controlling the influence of gender,it was found that MHR was positively correlated with left atrial di- ameter (LAD) ,left ventricular end-diastolic diameter (LVEDD) ,left ventricular end-systolic diameter (LVESD) and NT-pro BNP.It was negatively correlated with LVEF.Correlation analysis showed that MHR was positively cor- related with left atrial diameter (LAD) ,left ventricular end-diastolic diameter (LVEDD) ,left ventricular end-sys- tolic diameter (LVESD) and NT-pro BNP (P<0. 05) ,and negatively correlated with LVEF (P<0. 05) .The di- agnostic value of MHR combined with NT-pro BNP ( AUC = 0. 983 ) was higher than that of NT-pro BNP alone (AUC = 0. 974) (P<0. 05) .These results suggested that MHR might be associated with cardiac remodeling and cardiac function in DCM.The higher the MHR , the more pronounced the cardiac remodeling of DCM,and the more severe the heart failure.The combination of MHR and NT-pro BNP might further improve the diagnostic efficacy of NT-pro BNP in chronic heart failure in DCM.
Conclusion
Clinically,MHR can be used as an evaluation index of the presence of chronic heart failure and the severity of HF in DCM patients.The combined measurement of MHR and NT-pro BNP may be more conducive to improve the sensitivity and specificity of the clinical diagnosis of DCM chronic HF,so as to identify and accurately implement the standardized treatment of DCM chronic HF earlier.


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