1.Establishment of high-throughput liquid chromatography tandem mass spectrometry method for determination of 53 per- and polyfluoroalkyl substances in serum
Zheng WANG ; Boya ZHANG ; Jiming ZHANG ; Chao FENG ; Yuanjie LIN ; Chunhua WU ; Dasheng LU ; Zhijun ZHOU
Journal of Environmental and Occupational Medicine 2024;41(4):375-383
Background Per- and polyfluoroalkyl substances (PFAS) are a class of persistent organic pollutants that possess potential toxicity to the human body. The production and utilization of diverse emerging PFAS have resulted in widespread human exposure. Therefore, it is imperative to establish a quantitative methodology encompassing a wide range of PFAS for a comprehensive assessment of human exposure to these compounds. Objective To establish a high-throughput quantitative method for the simultaneous determination of 53 PFAS in human serum based on ultra-high-performance liquid chromatography-Q Exactive high resolution mass spectrometry (UPLC-Q Exactive HRMS). Methods The extraction recoveries of hydrophilic-lipophilic balance (HLB) column, weak anionexchange (WAX) column, and 96-well WAX μElution plate were compared to select the SPE column with the highest recovery. The retention time and peak shape of the target compounds were compared between ACQUITY UPLC BEH C18 column and Accucore aQ column, and the more cost-effective column was chosen. The effects of adding different levels of ammonium formate (0, 2, 5 and 10 mmol·L−1) in mobile phase on peak shape and target response were compared to determine the optimal buffer salt concentration. The optimal spray voltage was obtained by comparing −2 kV and −4 kV. The proposed method was validated from the aspects of selectivity, standard curve, limits of detection, precision, accuracy, and matrix effect. The method was applied to 142 umbilical serum samples. Results The best recovery rate (64%-118%) was achieved by using 96-well WAX μElution plate. The optimal separation and peak shape were obtained by utilizing Accucore aQ column with H2O-methanol (containing 5 mmol·L−1 ammonium formate) as the mobile phase. Less in-source collision and better target response were observed when the spray voltage was set to −2 kV. All target analytes had a good linearity, with R2 > 0.99. The limits of detection ranged from 0.01 to 0.50 μg·L−1, and the recovery ranged from 69% to 127% with the precision less than 26%. A total of 31 PFAS were detected in the 142 actual samples, among which 14 PFAS had a detection frequency over 50%. Perfluorooctanoic acid showed the highest median concentration of 4.16 μg·L−1, followed by 6:2 chlorinated polyfluorinated ether sulfonate and perfluorooctane sulfonates (3.50 μg·L−1 and 1.59 μg·L−1, respectively). Conclusion In this study, we establish a UPLC-Q Excative HRMS method for simutanious determination of 53 PFAS concentrations in serum. This method has the advantages of wide coverage of PFAS, good selectivity, and easy operation, and is suitable for biological detection with a large sample size.
2.Relationship between serum MBL,HRG,IL-23/IL-17 inflammatory axis and cerebral vasospasm and prognosis in patients with aneurysmal subarachnoid hemorrhage after interventional embolization
Chen SHEN ; Wei SHI ; Yuanjie ZHANG ; Zhirong YANG ; Huayi CHENG
International Journal of Laboratory Medicine 2024;45(2):134-140
Objective To investigate the relationship between serum mannan binding lectin(MBL),histi-dine rich glycoprotein(HRG),interleukin(IL)-23/IL-17 inflammatory axis and cerebral vasospasm(CVS)and prognosis in patients with aneurysmal subarachnoid hemorrhage(aSAH)after interventional emboliza-tion.Methods A total of 195 patients with aSAH who underwent interventional embolization treatment in the hospital from March 2019 to February 2022 were selected and were divided into no CVS group(126 cases),mild CVS group(18 cases),moderate CVS group(39 cases),and severe CVS group(12 cases)according to the occurrence and severity of CVS detected by digital subtraction angiography at the 4th postoperative day.The levels of serum MBL,HRG,IL-23 and IL-17 among the four groups before and 3 d after surgery were compared.The patients were followed up for 6 months and divided into good prognosis group(137 cases)and poor prognosis group(58 cases)according to their prognosis.Factors influencing poor prognosis in aSAH pa-tients were analyzed by multivariate Logistic regression model.The predictive value of serum MBL,HRG,IL-23,IL-17 levels and their combined application models for poor prognosis in patients with aSAH was analyzed by receiver operating characteristic(ROC)curve.Results The incidence rate of CVS after interventional em-bolization was 35.38%in 195 patients with aSAH.3 d after surgery,the serum levels of MBL,IL-23 and IL-17 in the mild,moderate,and severe CVS groups were higher than those in the no CVS group,those in the severe CVS group were higher than those in the moderate CVS group,those in the moderate CVS group were higher than those in the mild CVS group(P<0.05).The serum HRG levels in the mild,moderate,and severe CVS groups were lower than those in the non CVS group,those in the severe CVS group were lower than those in the moderate CVS group,those in the moderate CVS group were lower than those in the mild CVS group(P<0.05).3 d after surgery,the levels of serum MBL,IL-23 and IL-17 in the four groups were higher than that before surgery,while the levels of serum HRG were lower than that before surgery(P<0.05).The pro-portions of patients with aneurysm diameter≥6 mm,number of aneurysms>1,surgery time>24 h,Hunt-Hess grade Ⅲ/Ⅳ and postoperative CVS,and serum levels of MBL,IL-23,and IL-17 on the 3rd day after sur-gery in the good prognosis group were lower than those in the poor prognosis group,and serum HRG levels at 3 d after surgery in the good prognosis group were higher than that in the poor prognosis group(P<0.05).Multivariate Logistic regression analysis showed that aneurysm diameter≥6 mm,Hunt-Hess grade Ⅲ/Ⅳ and postoperative CVS,elevated serum levels of MBL,IL-23,and IL-17 and decreased HRG level at 3 d after sur-gery were independent risk factors for poor prognosis in aSAH patients(P<0.05).ROC results showed that serum levels of MBL,HRG,IL-23,and IL-17 at 3 d after surgery had certain predictive power for poor progno-sis in patients with aSAH.The predictive model with the combined application of four indicators had relatively high efficiency(the area under the curve was 0.853).Conclusion Elevated levels of MBL,IL-23,IL-17,and decreased HRG levels in aSAH patients after interventional embolization could increase the risk of CVS and are associated with poor prognosis in aSAH patients after interventional embolization.The above indicators have a certain predictive power for poor prognosis in aSAH patients.
3.The predictive value of serum sTWEAK,Netrin-1 combined with APACHE Ⅱ score for poor prognosis in patients with severe craniocerebral injury after surgery
Chen SHEN ; Wei SHI ; Yuanjie ZHANG ; Zhirong YANG ; Huayi CHENG
International Journal of Laboratory Medicine 2024;45(4):404-409,415
Objective To investigate the predictive value of serum soluble tumor necrosis factor-like weak inducer of apoptosis(sTWEAK)and Netrin-1 combined with acute physiology and chronic health evaluationⅡ(APACHE Ⅱ)score for poor prognosis in patients with severe craniocerebral injury after surgery.Methods Totally 120 patients with severe craniocerebral injury admitted to a hospital from June 2020 to June 2022 were divided into good prognosis group and poor prognosis group according to the prognosis 30 days af-ter surgery.The serum levels of sTWEAK,Netrin-1 and APACHE Ⅱ score were compared between the two groups.Univariate and multivariate Logistic regression were used to analyze the influencing factors of poor prognosis in patients with severe craniocerebral injury,and the prediction model of serum sTWEAK,Netrin-1 and APACHE Ⅱ score combined was constructed.The predictive value of serum sTWEAK,Netrin-1 level and APACHE Ⅱ score in patients with severe craniocerebral injury after surgery was analyzed by receiver operat-ing characteristic(ROC)curve.Results The duration of intensive care unit stay in the poor prognosis group was longer than that in the good prognosis group,and the albumin level,Glasgow Coma scale and serum Ne-trin-1 level at admission were lower than those in the good prognosis group.The proportion of multiple brain contusion and laceration,the proportion of mechanical ventilation,APACHE Ⅱ score at admission and the lev-els of serum sTWEAK,blood creatinine and blood urea nitrogen were higher than those in the group with good prognosis,and the differences were statistically significant(P<0.05).Multivariate Logistic regression analysis showed that multiple brain contusion and laceration,decreased Netrin-1 level,increased APACHE Ⅱscore and increased sTWEAK level at admission were risk factors for poor prognosis in patients with severe craniocerebral injury(P<0.05).ROC curve analysis showed that the area under the curve and 95%CI of ser-um sTWEAK,Netrin-1 and APACHE Ⅱ scores were 0.742(0.552-0.925),0.731(0.488-0.963),0.714(0.502-0.911)and 0.882(0.795-0.947)respectively when the three indexes were used alone and in com-bination.Conclusion Serum sTWEAK and Netrin-1 combined with APACHE Ⅱ score have good predictive value for the poor prognosis of patients with severe craniocerebral injury after surgery,and can provide refer-ence for the formulation of clinical treatment.
4.Construction and operation of the multi-level medical security system of the West China Women and Children Alliance
Jia LIU ; Tianyu JIANG ; Hanmin LIU ; Ying SHAN ; Shihao ZHANG ; Lianrui XIANG ; Yuanjie LIU
Chinese Journal of Hospital Administration 2024;40(1):12-16
Medical mutual aid is an important component of multi-level medical security system. West China Second University Hospital of Sichuan University led the establishment of the pediatric specialty alliance " West China Women and Children Alliance". Based on customized and inclusive mutual insurance product " Family Doctor Mutual Aid Plan", the alliance implemented key links such as mutual aid product forms, patient risk protection, institutional financing and hematopoiesis, and distribution of benefits to all parties, explored innovative mutual aid funding, payment, and incentive mechanisms, forming a closed-loop pediatric tiered diagnosis and treatment service system with the Mutual Aid Plan as the core. This system operated continuously under the " Four-in-One" framework, stimulating the integration of medical insurance and service supply systems while enhancing the synergistic effect between mutual insurance and social security. It has formed a distinctive health-centered multi-level medical security system within the alliance, and could provide reference for the construction and exploration of hierarchical diagnosis and treatment system.
5.Stability of Mandelonitrile in Commonly Used Solvents and Its Determination in Jian’er Qingjie Mixture
Yuanjie ZHANG ; Lan ZHOU ; Wenmei HAO ; Lyu HUANG ; Zheyuan LI
Chinese Journal of Modern Applied Pharmacy 2024;41(1):48-53
OBJECTIVE
To establish an HPLC method for investigating the stability of mandelonitrile in commonly used solvents and quantitation determination of mandelonitrile in Jian’er Qingjie mixture.
METHODS
The assay was performed on an Agilent TC-C18(250 mm×4.6 mm, 5 μm) column with a mobile phase consisting of acetonitrile-0.1% phosphoric acid(23∶27) pumped at a flow rate of 1.0 mL·min–1. The column temperature was 30 ℃ and the detection wavelength was set at 207 nm. The stability of the mandelonitrile solution prepared with solvents such as methanol, 95% ethanol, acetonitrile, water, phosphoric acid solution with pH 2.0−6.0, and acetonitrile solution containing 1.0% glacial acetic acid was investigated using the peak reduction rate as the indicator.
RESULTS
Mandelonitrile was labile in methanol, 95% ethanol or water and relatively stable in acetonitrile. The standard solutions of mandelonitrile prepared with phosphoric acid solutions at pH 2.0−3.5 or acetonitrile containing 1.0% glacial acetic acid were stable in 12 h. The linear range of mandelonitrile was 1.033−294.987 µg·mL–1(r=0.999 9) and the average recovery was 97.4% with RSD of 0.6%(n=9). The content range of mandelonitrile in 16 batches of Jian’er Qingjie mixture produced by 5 manufactures was 3.854−154.578 µg·mL–1.
CONCLUSION
The established method is simple and accurate. It can be used for the quality control of Jian’er Qingjie mixture. For almond aromatic water and its preparations, the influence of solvent on stability of mandelonitrile should be noticed.
6.Effect of combination of partial body weight support and functional electrical stimulation on lower limb motor function after stroke
Xingxiu XIONG ; Zhenghui ZHANG ; Chunyan DENG ; Yunbo LI ; Zhenpeng CHEN ; Yuanjie LI ; Jing SONG
Chinese Journal of Rehabilitation Theory and Practice 2024;30(5):554-559
Objective To observe the effect of combination of partial body weight support and functional electrical stimulation on lower limb motor function for stroke patients. Methods From January,2023 to February,2024,60 stroke patients from Rehabilitation Hospital of Chancheng District People's Hospital in Foshan City were randomly divided into control group(n=30)and observation group(n=30).The control group received routine rehabilitation,while the observation group received a combination of ce-lestial orbit system and functional electrical stimulation in addition,for three weeks.They were assessed with Balance assessment and training system,Berg Balance Scale(BBS),Fugl-Meyer Assessment-Lower Extremities(FMA-LE)and Holden Functional Ambulation Category(FAC)before and after treatment. Results X-axis trajectory length,average speed of swaying,total wobble trajectory,Y-axis trajectory length,trajectory length per unit area,BBS score,FMA-LE score and FAC score improved in both groups after treatment(|t|>4.809,P<0.001);and all the indexes improved more in the observation group than in the control group(|t|>2.268,P<0.05),except X-axis trajectory length and average speed of swaying. Conclusion Supplement of the combination of partial body weight support and functional electrical stimulation is more effective on lower limb motor function,balance and walking for stroke patients.
7.Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients (version 2024)
Yao LU ; Yang LI ; Leiying ZHANG ; Hao TANG ; Huidan JING ; Yaoli WANG ; Xiangzhi JIA ; Li BA ; Maohong BIAN ; Dan CAI ; Hui CAI ; Xiaohong CAI ; Zhanshan ZHA ; Bingyu CHEN ; Daqing CHEN ; Feng CHEN ; Guoan CHEN ; Haiming CHEN ; Jing CHEN ; Min CHEN ; Qing CHEN ; Shu CHEN ; Xi CHEN ; Jinfeng CHENG ; Xiaoling CHU ; Hongwang CUI ; Xin CUI ; Zhen DA ; Ying DAI ; Surong DENG ; Weiqun DONG ; Weimin FAN ; Ke FENG ; Danhui FU ; Yongshui FU ; Qi FU ; Xuemei FU ; Jia GAN ; Xinyu GAN ; Wei GAO ; Huaizheng GONG ; Rong GUI ; Geng GUO ; Ning HAN ; Yiwen HAO ; Wubing HE ; Qiang HONG ; Ruiqin HOU ; Wei HOU ; Jie HU ; Peiyang HU ; Xi HU ; Xiaoyu HU ; Guangbin HUANG ; Jie HUANG ; Xiangyan HUANG ; Yuanshuai HUANG ; Shouyong HUN ; Xuebing JIANG ; Ping JIN ; Dong LAI ; Aiping LE ; Hongmei LI ; Bijuan LI ; Cuiying LI ; Daihong LI ; Haihong LI ; He LI ; Hui LI ; Jianping LI ; Ning LI ; Xiying LI ; Xiangmin LI ; Xiaofei LI ; Xiaojuan LI ; Zhiqiang LI ; Zhongjun LI ; Zunyan LI ; Huaqin LIANG ; Xiaohua LIANG ; Dongfa LIAO ; Qun LIAO ; Yan LIAO ; Jiajin LIN ; Chunxia LIU ; Fenghua LIU ; Peixian LIU ; Tiemei LIU ; Xiaoxin LIU ; Zhiwei LIU ; Zhongdi LIU ; Hua LU ; Jianfeng LUAN ; Jianjun LUO ; Qun LUO ; Dingfeng LYU ; Qi LYU ; Xianping LYU ; Aijun MA ; Liqiang MA ; Shuxuan MA ; Xainjun MA ; Xiaogang MA ; Xiaoli MA ; Guoqing MAO ; Shijie MU ; Shaolin NIE ; Shujuan OUYANG ; Xilin OUYANG ; Chunqiu PAN ; Jian PAN ; Xiaohua PAN ; Lei PENG ; Tao PENG ; Baohua QIAN ; Shu QIAO ; Li QIN ; Ying REN ; Zhaoqi REN ; Ruiming RONG ; Changshan SU ; Mingwei SUN ; Wenwu SUN ; Zhenwei SUN ; Haiping TANG ; Xiaofeng TANG ; Changjiu TANG ; Cuihua TAO ; Zhibin TIAN ; Juan WANG ; Baoyan WANG ; Chunyan WANG ; Gefei WANG ; Haiyan WANG ; Hongjie WANG ; Peng WANG ; Pengli WANG ; Qiushi WANG ; Xiaoning WANG ; Xinhua WANG ; Xuefeng WANG ; Yong WANG ; Yongjun WANG ; Yuanjie WANG ; Zhihua WANG ; Shaojun WEI ; Yaming WEI ; Jianbo WEN ; Jun WEN ; Jiang WU ; Jufeng WU ; Aijun XIA ; Fei XIA ; Rong XIA ; Jue XIE ; Yanchao XING ; Yan XIONG ; Feng XU ; Yongzhu XU ; Yongan XU ; Yonghe YAN ; Beizhan YAN ; Jiang YANG ; Jiangcun YANG ; Jun YANG ; Xinwen YANG ; Yongyi YANG ; Chunyan YAO ; Mingliang YE ; Changlin YIN ; Ming YIN ; Wen YIN ; Lianling YU ; Shuhong YU ; Zebo YU ; Yigang YU ; Anyong YU ; Hong YUAN ; Yi YUAN ; Chan ZHANG ; Jinjun ZHANG ; Jun ZHANG ; Kai ZHANG ; Leibing ZHANG ; Quan ZHANG ; Rongjiang ZHANG ; Sanming ZHANG ; Shengji ZHANG ; Shuo ZHANG ; Wei ZHANG ; Weidong ZHANG ; Xi ZHANG ; Xingwen ZHANG ; Guixi ZHANG ; Xiaojun ZHANG ; Guoqing ZHAO ; Jianpeng ZHAO ; Shuming ZHAO ; Beibei ZHENG ; Shangen ZHENG ; Huayou ZHOU ; Jicheng ZHOU ; Lihong ZHOU ; Mou ZHOU ; Xiaoyu ZHOU ; Xuelian ZHOU ; Yuan ZHOU ; Zheng ZHOU ; Zuhuang ZHOU ; Haiyan ZHU ; Peiyuan ZHU ; Changju ZHU ; Lili ZHU ; Zhengguo WANG ; Jianxin JIANG ; Deqing WANG ; Jiongcai LAN ; Quanli WANG ; Yang YU ; Lianyang ZHANG ; Aiqing WEN
Chinese Journal of Trauma 2024;40(10):865-881
Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.
8.Isolation,identification,gene sequence analysis and pathogenicity of H3N2 subtype swine influenza virus
Chaoyang CHEN ; Yingxue ZHANG ; Congcong XU ; Yuanjie SHI ; Long CAO ; Xijun YAN ; Lijie TANG
Chinese Journal of Veterinary Science 2024;44(9):1841-1847
The nasal swab samples of swine influenza(SI)suspected pigs were collected and tested for H3 subtype swine influenza virus(SIV)positive by RT-qPCR.The positive samples were inoc-ulated into SPF chicken embryos for virus isolation.The full genome sequencing and sequence anal-ysis of the isolated H3N2 subtype SIV were conducted,and its pathogenicity was studied.The re-sults showed that a strain of SIV was successfully isolated and identified as H3N2 subtype by RT-PCR,named A/Swine/Yunnan/KM/06/2023(H3N2).The BLSAT results showed that the eight segments of SIV H3N2 KM had the highest homology with eight different strains of swine influ-enza or human influenza viruses,reaching 95.41%-97.49%.The HA and NA segments were de-rived from H3N2 subtype SIV,the NP segment was derived from H1N1 subtype human influenza virus,the M segment was derived from H1N2 subtype SIV,and all other segments were derived from H1N1 subtype SIV.The key receptor sites(190D,223V,226I,228S)of HA protein remained unchanged.The pathogenicity experiment results showed that infected piglets exhibited symptoms such as fever,sneezing,runny nose,the virus could be detoxified to the outside through the nasal cavity,and the lungs had different degrees of lesion.Immunohistochemistry(IHC)showed that the virus could replicate in the lungs.In conclusion,a strain of H3N2 subtype SIV was successfully iso-lated,and the genetic evolution,molecular characteristics and pathogenicity of the virus were stud-ied.It revealed that H3N2 subtype SIV is constantly evolving and had pathogenicity to piglets,pro-viding a reference for monitoring and preventing SIV epidemics in China,and provided a candidate strain for SI vaccine development.
9.Jianpi Yangzheng Xiaozheng Decoction Affect Proliferation and Stemness of Gastric Cancer HGC-27 Cells by Inhibiting Aerobic Glycolysis
Heyun TAO ; Yuanjie LIU ; Jiepin LI ; Shuhong ZENG ; Ying ZHANG ; Shenlin LIU ; Xi ZOU
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(11):82-88
ObjectiveTo observe the effect of Jianpi Yangzheng Xiaozheng decoction (JYXD) on the proliferation and stemness of the human gastric cancer (GC) cell line HGC-27 by inhibiting aerobic glycolysis, and explore the underlying mechanism. MethodMethyl thiazolyl tetrazolium (MTT) assay was employed to determine the survival rate and chemotherapy sensitivity of HGC-27 cells treated with JYXD (0.25, 0.5, 1, 2, 4, 8, 16, 32 g·L-1). Colony formation assay was employed to detect the effect of JYXD (2, 4, 8 g·L-1) on the colony formation of the cells. The aerobic glycolysis level of HGC-27 cells after treatment with JYXD was measured by glucose assay kit and lactic acid assay kit. The proportion of stem cell subsets in HGC-27 cells was detected by flow cytometry. Western blot was employed to determine the expression of glycolysis-associated proteins such as lactate dehydrogenase (LDH), hexokinase 2 (HK2), glucose transporter 1 (GLUT1), and pyruvate kinase isozyme M2 (PKM2), and the expression of stemness-associated proteins such as octamer-binding transcription factor 4 (OCT4), SRY-box transcription factor 2 (SOX2), and Nanog. ResultJYXD (0.5, 1, 2, 4, 8, 16, 32 g·L-1) inhibited the activity of HGC-27 cells (P<0.05, P<0.01), with the inhibitory concentration 50(IC50) of 4.83 g·L-1, and it improved the sensitivity of HGC-27 cells to cisplatin chemotherapy. Compared with the control group, JYXD (2, 4, 8 g·L-1) reduced the colony formation number of HGC-27 cells (P<0.01) in a concentration-dependent manner. Flow cytometry showed that compared with that in the control group, the proportion of CD44+CD24+ALDH+ population in the cells treated with JYXD (2, 4, 8 g·L-1) decreased (P<0.05). In addition, JYXD (2, 4, 8 g·L-1) inhibited the glucose uptake and lactic acid production of HGC-27 cells. Western blot showed that compared with the control group, JYXD (2, 4, 8 g·L-1) down-regulated the expression levels of SOX2, Nanog, OCT4, PKM2, LDH, GLUT1, and HK2 (P<0.05, P<0.01) in a concentration-dependent manner. ConclusionJYXD may inhibit the proliferation and reduce the stemness of HGC-27 cells by regulating the aerobic glycolysis.
10.Ultrasmall iron-quercetin metal natural product nanocomplex with antioxidant and macrophage regulation in rheumatoid arthritis.
Zhihui HAN ; Xiang GAO ; Yuanjie WANG ; Shuning CHENG ; Xiaoyan ZHONG ; Yong XU ; Xiaozhong ZHOU ; Zengli ZHANG ; Zhuang LIU ; Liang CHENG
Acta Pharmaceutica Sinica B 2023;13(4):1726-1739
Oxidative stress, due to the disruption of the balance between reactive oxygen species (ROS) generation and the antioxidant defense system, plays an important role in the pathogenesis of rheumatoid arthritis (RA). Excessive ROS leads to the loss of biological molecules and cellular functions, release of many inflammatory mediators, stimulate the polarization of macrophages, and aggravate the inflammatory response, thus promoting osteoclasts and bone damage. Therefore, foreign antioxidants would effectively treat RA. Herein, ultrasmall iron-quercetin natural coordination nanoparticles (Fe-Qur NCNs) with excellent anti-inflammatory and antioxidant properties were constructed to effectively treat RA. Fe-Qur NCNs obtained by simple mixing retain the inherent ability to remove ROS of quercetin and have a better water-solubility and biocompatibility. In vitro experiments showed that Fe-Qur NCNs could effectively remove excess ROS, avoid cell apoptosis, and inhibit the polarization of inflammatory macrophages by reducing the activation of the nuclear factor-κ-gene binding (NF-κB) pathways. In vivo experiments showed that the swollen joints of mice with rheumatoid arthritis treated with Fe-Qur NCNs significantly improved, with Fe-Qur NCNs largely reducing inflammatory cell infiltration, increasing anti-inflammatory macrophage phenotypes, and thus inhibiting osteoclasts, which led to bone erosion. This study demonstrated that the new metal-natural coordination nanoparticles could be an effective therapeutic agent for the prevention of RA and other diseases associated with oxidative stress.


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