1.National bloodstream infection bacterial resistance surveillance report 2023: Gram-positive bacteria
Chaoqun YING ; Jinru JI ; Zhiying LIU ; Qing YANG ; Haishen KONG ; Jiangqin SONG ; Hui DING ; Yanyan LI ; Yuanyuan DAI ; Haifeng MAO ; Pengpeng TIAN ; Lu WANG ; Yongyun LIU ; Yizheng ZHOU ; Jiliang WANG ; Yan JIN ; Donghong HUANG ; Hongyun XU ; Peng ZHANG ; Xinhua QIANG ; Hong HE ; Lin ZHENG ; Junmin CAO ; Zhou LIU ; Ying HUANG ; Yan GENG ; Haiquan KANG ; Dan LIU ; Guolin LIAO ; Lixia ZHANG ; Fenghong CHEN ; Yanhong LI ; Baohua ZHANG ; Haixin DONG ; Xiaoyan LI ; Donghua LIU ; Qiuying ZHANG ; Xuefei HU ; Liang GUO ; Sijin MAN ; Dijing SONG ; Rong XU ; Youdong YIN ; Kunpeng LIANG ; Aiyun LI ; Zhuo LI ; Hongxia HU ; Guoping LU ; Jinhua LIANG ; Qiang LIU ; Yinqiao DONG ; Jilu SHEN ; Shuyan HU ; Liang LUAN ; Jian LI ; Ling MENG ; Dengyan QIAO ; Xiusan XIA ; Bo QUAN ; Dahong WANG ; Chunhua HAN ; Xiaoping YAN ; Fei LI ; Shifu WANG ; Ping SHEN ; Yunbo CHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2025;18(2):118-132
Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System(BRICS)during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute(CLSI). Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus( n=1 544,35.2%),coagulase-negative Staphylococci( n=1 441,32.9%), Enterococcus faecium( n=574,13.1%), Enterococcus faecalis( n=385,8.8%),and α-hemolytic Streptococci( n=187,4.3%). The prevalence of methicillin-resistant Staphylococcus aureus(MRSA)and methicillin-resistant coagulase-negative Staphylococci(MRCNS)was 26.2%(405/1 544)and 69.8%(1 006/1 441),respectively. Notably,all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility(>97.0%)to cephalobiol,rifampicin,trimethoprim-sulfamethoxazole,linezolid,minocycline,tigecycline,and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium(resistance to vancomycin and teicoplanin:both 1.7%)compared to Enterococcus faecalis(both 0.3%). The detection rates of MRSA and MRCNS exhibited significant regional variations across the country( χ2=17.674 and 148.650,respectively,both P<0.001). No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA( χ2=14.111, P<0.001)and MRCNS( χ2=4.828, P=0.028)in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA( χ2=18.986, P<0.001)and MRCNS( χ2=4.477, P=0.034)in less developed regions(per capita GDP
2.National bloodstream infection bacterial resistance surveillance report (2023) : Gram-negative bacteria
Jinru JI ; Zhiying LIU ; Chaoqun YING ; Qing YANG ; Haishen KONG ; Jiangqin SONG ; Hui DING ; Yanyan LI ; Yuanyuan DAI ; Haifeng MAO ; Pengpeng TIAN ; Lu WANG ; Yongyun LIU ; Yizheng ZHOU ; Jiliang WANG ; Yan JIN ; Donghong HUANG ; Hongyun XU ; Peng ZHANG ; Xinhua QIANG ; Hong HE ; Lin ZHENG ; Junmin CAO ; Zhou LIU ; Ying HUANG ; Yan GENG ; Haiquan KANG ; Dan LIU ; Guolin LIAO ; Lixia ZHANG ; Fenghong CHEN ; Yanhong LI ; Baohua ZHANG ; Haixin DONG ; Xiaoyan LI ; Donghua LIU ; Qiuying ZHANG ; Xuefei HU ; Liang GUO ; Sijin MAN ; Dijing SONG ; Rong XU ; Youdong YIN ; Kunpeng LIANG ; Aiyun LI ; Zhuo LI ; Hongxia HU ; Guoping LU ; Jinhua LIANG ; Qiang LIU ; Yinqiao DONG ; Jilu SHEN ; Shuyan HU ; Liang LUAN ; Jian LI ; Ling MENG ; Dengyan QIAO ; Xiusan XIA ; Bo QUAN ; Dahong WANG ; Chunhua HAN ; Xiaoping YAN ; Fei LI ; Shifu WANG ; Ping SHEN ; Yunbo CHEN ; Yonghong XIAO
Chinese Journal of Clinical Infectious Diseases 2025;18(1):47-62
Objective:To report the results of bacterial resistant investigation collaborative system(BRICS)on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023,and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute(CLSI). WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period,11 492 strains of Gram-negative bacteria were collected from 60 hospitals,of which 10 098(87.9%)were Enterobacterales and 1 394(12.1%)were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli(50.0%), Klebsiella pneumoniae(26.1%), Pseudomonas aeruginosa(5.1%), Acinetobacter baumannii complex(5.0%)and Enterobacter cloacae complex(4.1%). The ESBL-producing rates in Escherichia coli, Klebsiella pneumoniae and Proteus mirablilis were 46.8%(2 685/5 741),18.3%(549/2 999)and 44.0%(77/175),respectively. The prevalence of carbapenem-resistant Escherichia coli(CREC)and carbapenem-resistant Klebsiella pneumoniae(CRKP)were 1.3%(76/5 741)and 15.0%(450/2 999);32.9%(25/76)and 78.0%(351/450)of CREC and CRKP were sensitive to ceftazidime/avibactam combination,respectively. 94.7%(72/76)and 90.2%(406/450)of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore,57.9%(44/76)and 79.1%(356/450)were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii(CRAB)complex was 64.6%(370/573),while more than 80.0% of CRAB complex was sensitive to tigecycline,eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa(CRPA)was 17.0%(99/581). There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China,with statistically significant differences in the prevalence of CREC,CRKP,CRPA and CRAB complex( χ2=10.6,28.6,10.8 and 19.3, P<0.05). The prevalence of ESBL-producing Escherichia coli, CREC,CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals( χ2=12.5,9.8,12.7 and 57.8,all P<0.01). Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China,and Escherichia coli is ranked in the top,while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend,CREC infecton maintains a low prevalence level,and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.
3.Efficacy and prognosis of preoperative treatment based on arterial infusion chemotherapy in patients with advanced gastric cancer: a real-world study
Xiaosong XIANG ; Feilong GUO ; Yu SU ; Long MA ; Donghong SHI ; Leilei LIU ; Guoli LI
Chinese Journal of Oncology 2025;47(2):183-192
Objective:To explore the efficacy and prognosis of preoperative treatment based on arterial infusion chemotherapy (PTAC) in patients with advanced gastric cancer.Methods:Clinical and follow-up data of 821 patients with advanced gastric cancer who received PTAC treatment at the General Hospital of the Eastern Theater Command of the People's Liberation Army from January 2001 to January 2021 were collected. According to the treatment regimen, patients were divided into the FLEEOX group (89 cases), the XEEOX group (196 cases), the SEEOX group (406 cases), and the SEEOX+PD-1 group (130 cases). The primary endpoint was the 3-year progression-free survival rate. Secondary endpoints included the 3-year overall survival rate, objective response rate, radical resection rate, major pathological response rate, and incidence of treatment associated adverse events.Results:After PTAC treatment, the objective response rate was 74.9% (615/821). A total of 671 patients underwent radical surgery, with a radical resection rate of 81.7% and an R0 resection rate of 70.2% (576/821). The pathological complete response rate was 16.7% (112/671), and the major pathological response rate was 32.2% (216/671). With an average follow-up of 27.7 months, the 3-year progression-free survival rate was 52.2%, and the 3-year overall survival rate was 55.8%. The 3-year progression-free survival rate of patients in the SEEOX+PD-1 group was 66.9%, the objective response rate was 83.8% (109/130), the major pathological response rate was 45.3% (53/117), and the radical resection rate was 90.0% (117/130), all of which were better than those in the XEEOX and SEEOX groups (all P<0.05). However, during the treatment period, three patients in the SEEOX+PD-1 group died from immune-related adverse events. Conclusion:PTAC treatment is an effective preoperative treatment method for advanced gastric cancer, and is expected to further improve the treatment effect when combined with immunotherapy such as PD-1 monoclonal antibodies.
4.Study on influencing factors of lung function injury in workers exposed to carbon industry in a city
Xiaochen SUN ; Hua SHAO ; Ning LI ; Peng HAN ; Tao WANG ; Fengjiang SONG ; Donghong SU ; Feng CUI
Chinese Journal of Industrial Hygiene and Occupational Diseases 2025;43(3):224-227
Objective:To investigate the influential factors of lung function injury in occupational exposure workers in carbon industry.Methods:In January 2024, a judgment sampling method was employed, with 230 occupational exposure workers in the carbon industry as the study subjects. They were divided into abnormal group and normal group according to whether there was lung function injury in occupational health examination. The basic information of workers in carbon industry was collected by questionnaire, their lung function was measured, urine and blood samples were collected after work, and 1-hydroxypyrene, 1-hydroxynaphthalene and 2-hydroxynaphthalene concentrations and the percentage of DNA in the comet tail and Olive tail distance in peripheral blood lymphocytes were determined. The differences in indicators of lung function, urine and blood samples between the two groups were compared by Mann-Whitney test and t-test. The influencing factors of lung function injury were analyzed by logistic regression. Results:The forced vital capacity (FVC) %[88% (86%, 92%) ], forced expiratory volume in the first second (FEV 1) %[92% (88%, 95%) ] and FEV 1.0/FVC%[96% (91%, 102%) ] of occupational exposure workers in the carbon industry in the normal lung function group ( n=118) were significantly higher than those in the abnormal lung function group [ n=112, 83% (80%, 87%), 84% (80%, 88%), 86% (79%, 91%) ], the differences were statistically significant ( P<0.05). 1-Hydroxypyrene[9.28 (2.96, 25.94) μg/g], 1-hydroxynaphthalene[2.48 (1.47, 4.37) μg/g], percentage of DNA in the comet tail [11.83% (5.30%, 21.45%) ] and Olive tail distance [2.30 (0.82, 4.77) μm] in the abnormal lung function workers was significantly higher than those in the normal group[2.57 (1.17, 9.34) μg/g, 1.70 (0.94, 2.89) μg/g, 6.75% (2.55%, 12.60%), 1.25 (0.43, 2.34) μm], and the differences were statistically significant ( P<0.05). Logistic regression analysis showed that sex, working age, job type, percentage of comet tail DNA in peripheral blood, Olive tail distance and 1-hydroxypyrene were all factors influencing lung function injury in occupational exposure workers in carbon industry ( P<0.05) . Conclusion:The percentage of DNA in the comet tail, Olive tail distance in peripheral blood lymphocytes and 1-hydroxypyrene may be markers of lung function injury in workers exposed to carbon industry. Working age and job type are occupational factors affecting lung function injury. Occupational protection should be strengthened and a reasonable operating system should be established to ensure the health of occupational workers.
5.Clinical distribution and drug resistance rates of Nocardia in a three-A hospital of Quanzhou from 2019 to 2024
Xihuan SUN ; Jiaming HUANG ; Peifen LI ; Yingying LIN ; Donghong HUANG
Chinese Journal of Nosocomiology 2025;35(17):2664-2668
OBJECTIVE To understand the distribution and drug susceptibility rates of clinical Nocardia isolates so as to provide bases for standardized clinical diagnosis and treatment.METHODS The characteristics of clinical dis-tribution of the Nocardia strains that were isolated from The Second Affiliated Hospital of Fujian Medical Univer-sity between Aug.2019 and Aug.2024 were retrospectively analyzed.The isolated strains were identified by means of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF MS),16S rRNA and rpoB gene sequencing were performed for the strains with low score,and the drug susceptibility testing was carried out by broth micro dilution method.RESULTS Totally 35 strains of Nocardia were isolated from clinical specimens in the five years,11 of which were Nocardia cyriacigeorgica,4 were Nocardia asiatica,3 were No-cardia farcinica,3 were Nocardia brasiliensis,3 were Nocardia sputorum,2 were Nocardia nova,2 were No-cardia otitidiscaviarum,2 were Nocardia beijingensis,2 were Nocardia concava,1 was Nocardia abscessus,1 was Nocardia pseudobrasiliensis,and 1 was Nocardia terpenica.Totally 85.71%of the strains were isolated from lower respiratory tract specimens including sputum,bronchoalveolar lavage fluid,bronchial brushing and lung puncture tissues,and 11.43%were isolated from skin and soft tissues.It was basically same in the male to female ratio for the patients with Nocardia infections,there were 18 cases of male and 17 cases of female.The elderly patients were dominant,and the patients aged more than 60 years old accounted for 51.43%.The strains were mainly isolated from respiratory medicine department and critical care medicine department.The drug sus-ceptibility rates of all the isolated strains to amikacin and linezolid were 100%,the drug susceptibility rates to sul-famethoxazole-trimethoprim were 97.14%,and the drug susceptibility rates to tobramycin,ceftriaxone and imi-penem were 80%,65.71%and 62.86%,respectively;the drug resistance rates to clarithromycin and ciprofloxa-cin were 65.71%and 62.86%,respectively.Among the major species of isolated Nocardia strains,the N.cyri-acigeorgica strains were all sensitive to sulfamethoxazole-trimethoprim,linezolid,tobramycin,amikacin,imipen-em and ceftriaxone,the strains were resistant to ciprofloxacin,and the drug resistance rate to clarithromycin reached up to 81.82%.CONCLUSIONS N.cyriacigeorgica is the predominant species of isolated Nocardia strains.The pulmonary infection is the major type of infection.There is little difference in the male to female ratio among the patients with Nocardia infection,and the elderly patients are dominant.Amikacin,linezolid and sulfame-thoxazole-trimethoprim are the most sensitive drugs,and the drug resistance rates of the stains to clarithromycin are high.
6.Development and application of an optimized focus-forming assay for quantitation of influenza A virus titer
Jia LI ; Qiaohong CHU ; Lingfang ZHANG ; Xuchang SHAN ; Tangqi WANG ; Ruiwen HAN ; Yujie JIANG ; Donghong WANG ; Baoying HUANG ; Yao DENG ; Wenjie TAN
Chinese Journal of Microbiology and Immunology 2025;45(1):45-52
Objective:To establish and optimize a novel method, focus forming assay (FFA), for quantitation of influenza A virus (FluA) and compare its application performance with traditional plague forming assay (PFA).Methods:The foci chromogenic effects of three peroxidase substrates in immunostaining were compared. The PFA and FFA methods were used to explore FluA incubation times and plaque morphology on 12-well plates, and to determine optimal incubation times and virus adsorption volumes for different FluA subtypes on 96-well plates. The correlation between FFA and PFA was evaluated, and the optimized FFA was applied to the in vitro antiviral efficacy analysis of Favipiravir and neutralization test against different subtypes of FluA. Results:TRUEBLUE substrate was identified as the optimal substrate for foci visualization. Compared with the PFA, the FFA showed improved sensitivity and reduced detection time in FluA titration, and good correlation was shown between the two methods′ results. By replacing the 96-well plate with the 12-well plate for FFA titration of different subtypes of FluA, the detection time was shortened, and the amount of serum samples used could be further reduced by optimizing the virus adsorption volume. The half-maximal effective concentration of favipiravir against influenza viruses assessed by the FFA and PFA methods showed no significant difference, and was consistent with the results obtained from quantitative PCR. Additionally, the focus reduction neutralization test and hemagglutination inhibition assays demonstrated strong correlation in determining antibody titers against FluA in serum neutralization assays.Conclusions:The improved FFA method developed here provides a more efficient experimental tool for FluA titration, antiviral drug screening and broad-spectrum vaccine evaluation.
7.The prognostic value of serum homocysteine, neutrophil to lymphocyte ratio and total imaging load score on cognition disorders in small cerebral vascular disease patients
Yunpeng SONG ; Donghong GUO ; Minxia LI
Chinese Journal of Postgraduates of Medicine 2025;48(12):1103-1107
Objective:To investigate the predictive value of serum homocysteine (Hcy), neutrophil to lymphocyte ratio (NLR) and total imaging load score on cognition disorders in patients with small cerebral vascular disease (CSVD).Methods:A total of 106 CSVD patients treated in Shanxi Hongdong County People's Hospital from June 2021 to June 2024 were retrospectively selected as the study objects. The Montreal Cognitive Assessment Scale (MoCA) was used to assess cognitive function. Among them, 43 patients with cognition disorders and 63 patients without cognition disorders were evaluated. Another 30 healthy subjects over 60 years old were selected as control group. General data and serum Hcy, NLR and other indicators of the three groups were compared, MRI examination was performed, and the total imaging load score was calculated. Logistic regression was used to analyze the risk factors of cognition disorders in CSVD patients, and receiver operating characteristic (ROC) curve was used to analyze the predictive value of Hcy, NLR and radiographic total load score for cognition disorders in CSVD patients.Results:The levels of Hcy, NLR and total imaging load scores in the CSVD group were higher than those in the CSVD group and the control group : (20.32 ± 3.24) μmol/L vs. (17.75 ± 2.81), (14.96 ± 3.84) μmol/L; 2.77 ± 0.75 vs. 2.27 ± 0.68, 1.93 ± 0.47; (1.28 ± 0.73) scores vs. (0.92 ± 0.55), (0.36 ± 0.21) scores, there were statistical differences ( P<0.05). The results of Logistic regression showed that Hcy, NLR and total load score were risk factors for cognition disorders ( P<0.05). The results of ROC curve showed that the area under the curve (AUC) of Hcy, NLR, total imaging load score combined prediction of cognition disorders was 0.798. Conclusions:Hcy, NLR and total imaging load score are risk factors for cognition disorders in CSVD, and have certain predictive value for cognition disorders.
8.Application of health belief model in blood pressure management in patients with moyamoya disease after cerebral vascular reconstruction surgery
Na LI ; Hongyan CHEN ; Xi REN ; Xinxin DONG ; Qinglin LIU ; Donghong ZHAO
Journal of Clinical Medicine in Practice 2025;29(12):120-124
Objective To explore the application effect of blood pressure management based on the health belief model in patients with moyamoya disease after cerebral vascular reconstruction sur-gery.Methods From February to July 2024,210 patients with moyamoya disease who underwent cerebral vascular reconstruction surgery in our hospital were selected as study subjects.They were randomly divided into control group and intervention group,with 105 cases in each group.The control group received routine nursing care,while the intervention group applied blood pressure management based on the health belief model on the basis of routine nursing care.The postoperative cerebral hy-perperfusion syndrome and blood pressure control status of the two groups were compared,and the Health Belief Scale and the Mishel Uncertainty in Illness Scale were used to evaluate the effects before and after intervention.Results A total of 203 patients completed the study,including 100 cases in the control group and 103 cases in the intervention group.There were statistically significant differ-ences in the incidence of cerebral hyperperfusion syndrome and the proportion of patients with blood pressure higher than baseline data between the two groups(P<0.05).After the intervention,there were statistically significant differences in the postoperative cerebral hyperperfusion syndrome status and blood pressure control status between the two groups(P<0.05).After intervention,there were statistically significant differences in the scores of susceptibility and health motivation dimensions as well as the total score in the Health Belief Scale between the intervention group and the control group(P<0.05).After the intervention,there were statistically significant differences in the scores of ambiguity and unpredictability dimensions as well as the total score in the Mishel Uncertainty in Ill-ness Scale between the intervention group and the control group(P<0.05).Conclusion Blood pressure management based on the health belief model can effectively control blood pressure,reduce the incidence of cerebral hyperperfusion,improve health beliefs,and reduce the sense of uncertainty about the disease.
9.Assessment of Left Atrial Function by 4D Auto Left Atrial Quantification Echocardiography for Differentiation of Pre-capillary and Post-capillary Pulmonary Hypertension
Cuiling LI ; Xinli LEI ; Fei XIAO ; Rui FAN ; Siying LIAO ; Donghong LIU ; Hong LIN ; Fengjuan YAO
Journal of Sun Yat-sen University(Medical Sciences) 2025;46(4):667-675
[Objective]To evaluate the utility of left atrial(LA)volume and strain measured by 4D auto left atrial quantification(4D auto LAQ)in differentiating pre-capillary from post-capillary pulmonary hypertension(PH),and to compare its discriminative performance with echocardiographic pulmonary to left atrial global strain ratio(ePLAGS).[Methods]A total of ninety-eight subjects with intermediate to high probability of PH were prospectively enrolled.Clinical history and laboratory data were collected.All patients underwent comprehensive transthoracic echocardiography,and LA volume and strain parameters were measured by dedicated commercial software for LA 4D analysis.[Results]Based on pulmonary arterial wedge pressure,patients were divided into pre-capillary PH group[n=39;mean age(53±24)years]and post-capillary PH group[n=59;mean age(57±18)years].Compared to the pre-capillary PH group,the post-capillary PH group showed significantly higher LAVImax,LAVImin and LAVIpreA but markedly lower LASr and LAScd.Multivariate logistic regression identified LAVImax[OR:1.40;95%CI:(1.052,1.872);P=0.021]and LAScd[OR:1.76;95%CI:(1.183,2.489);P=0.004]as independent predictors of post-capillary PH.ROC analysis demonstrated that LAVImax(AUC=0.82,P<0.001)and LAScd(AUC=0.78,P<0.001)had strong discriminating power for predicting post-capillary PH group,with optimal cutoff values of 35.69 mL/m2(sensitivity 86%,specificity 74%)and-9%(sensitivity 80%,specificity70%).[Conclusion]LAVImax and LAScd measured with 4D auto LAQ are robust parameters for distinguishing pre-capillary PH from post-capillary PH.
10.Construction of hyperuricemic mouse model with Uox gene knockout based on CRISPR/Cas9 system
Yiwei ZHANG ; Weihu LONG ; Donghong TANG ; Shengtao FAN ; Peng WANG ; Chenyun WANG ; Zheli LI ; Zhangqiong HUANG ; Yousong YE
Acta Laboratorium Animalis Scientia Sinica 2025;33(3):411-419
Objective To construct a uricase-deficient mouse model with stable inheritance using the CRISPR/Cas9 system,and evaluate its ability to simulate the disease characteristics of patients with hyperuricemia.Methods Double single guide RNAs(sgRNAs)were designed on both sides of exon 2~4 of the Uox gene.sgRNA and Cas9 mRNA for gene knockout were microinjected into the fertilized eggs of mice.After culture for 2~4 h,the embryos were transferred to surrogate mother mice to produce an F0 generation.Uox-knockout mice were identified by polymerase chain reaction and sequencing analysis.Positive mice were then mated with wild-type(WT)mice to produce an F1 generation,and heterozygous female and male F1 mice were then selected to obtain homozygous F2 mice.Serum and urine levels of uric acid,creatinine,and urea,and serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels were detected and compared between homozygous and wild-type mice.Pathological changes in kidney and liver tissues were observed by hematoxylin and eosin and Masson staining.Results Urine levels of serum uric acid(male:(4116.8±1928.1)μmol/L,P<0.001;female:(2998.0±547.7)μmol/L,P<0.01)and serum levels of uric acid(male:(478.4±114.6)μmol/L,P<0.001;female:(507.7±129.6)μmol/L,P<0.001),creatinine((91.8±55.6)μmol/L,P<0.001),urea((28.6±13.9)mmol/L,P<0.05),ALT((53.3±23.3)U/L,P<0.01),and AST((203.3±70.3)U/L,P<0.001)were significantly increased in Uox-/-mice compared with WT mice.Histopathological examination showed moderate hepatocyte degeneration in the liver,moderate-to-severe tubular cystic dilation,degeneration,and fibrosis in the kidney,glomerular hypertrophy and hyperplasia,small-vessel dilation and congestion,and infiltration of stromal monocytes and lymphocytes in Uox-/-mice.Conclusions We successfully established a homozygous uricase-deficient mouse strain using CRISPR/Cas9 technology,as a suitable animal model for research in the field of hyperuricemia.

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