1.Near-infrared fluorescence imaging for intraoperative neuroimaging:current applications and future development
Wenping GAO ; Zhihua ZHANG ; Fei HAN ; Weiguo HAO
Chinese Journal of Tissue Engineering Research 2024;28(32):5225-5230
BACKGROUND:Existing neuroimaging techniques,including magnetic resonance imaging,computed tomography,and high-resolution ultrasound,lack the capability to provide real-time intraoperative positioning images to surgeons.However,the clinical implementation of near-infrared fluorescence imaging technology has made it possible to directly visualize surgical target areas,offering a novel solution for real-time nerve identification during surgery. OBJECTIVE:To provide a summary and overview of the research progress in near-infrared fluorescence imaging technology for intraoperative neuroimaging. METHODS:The first author used the computer to search for the documents published from January 2010 to July 2023 in WanFang,CNKI,and PubMed with the key words of"near-infrared fluorescence imaging,optical imaging,nerve imaging"in Chinese and English.A few classic old documents were also included.Initial screening was performed by reading the titles and abstracts;duplicate,low-quality,and irrelevant content documents were excluded.A total of 69 articles were finally included for review. RESULTS AND CONCLUSION:Near-infrared fluorescence imaging guided by indocyanine green has been clinically used to identify and locate tubular organs such as blood vessels,ureters,and bile ducts,as well as various tumors during surgery.This technique is currently considered a well-established imaging method in precision surgery.In the field of intraoperative neurofluorescence imaging,indocyanine green is currently the only near-infrared fluorescent dye used in clinical research.The ideal neuroimaging agent should possess certain characteristics,including easy administration in the perioperative period,logD between 0.5 and 3 at pH=7.4,molecular mass below 500 Da,excitation and emission wavelengths within the near-infrared window,long-term retention in nerve tissue,high signal-to-background ratio,and high safety.In the future,the development of near-infrared neurofluorescence imaging agents should focus on synthesizing complexes of indocyanine green and neural-specific targets.This technology not only enables intraoperative neurofluorescence imaging,but also holds promising prospects for in-situ monitoring of nerve regeneration and diagnosis of neurological diseases.
2.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.
3.Enhancement of anti-tumor effect of immune checkpoint inhibitor anti-PD-L1 by shenqifuzheng injection and the mechanism study
Zhihua ZHOU ; Jingwen CHANG ; Yuanyuan YAN ; Yanan QI ; Jingjing HAN ; Xinyi ZHU ; Chen YU ; Hongyan WU ; Fangtian FAN
Chinese Journal of Clinical Pharmacology and Therapeutics 2024;29(7):792-799
AIM:To investigate of the effect of Shenqifuzheng injection(SFI)combined with PD-L1 antibody on tumor immune microenvironment and its efficacy.METHODS:A subcutaneous transplanta-tion tumor model for B16F10-LUC melanoma was created.The expression of Ki67,CD31,CD8,CD16,CD163,FOXP3,LY6C,LY6G with labeling antibodies was used to detect CD8+T cells,Treg cells,NK cells,MDSCs cells,centrocytes,and granulocytes in the tumor tissues via immunohistochemistry.Flow cy-tometry was used to measure the ratios of CD11c+,IA/IE+,and CD80+cells in splenic tissue,as well as the ratios of CD8+T,CD4+T,and Treg cells in tumor tissue.Additionally,granulocyte count and NK cell expression were analyzed.RESULTS:The immuno-histochemistry results indicate that the drug admin-istration group effectively suppressed tumor angio-genesis and cell proliferation,while decreasing the expression level of immunosuppressive cytokines CD4+T cells,Treg cells,MDSCs and centroblasts.Ad-ditionally,CD8 and NK cell infiltration was promot-ed compared to the control group.The results of the flow analysis demonstrated a significant in-crease in the expression level of CD8+T cells within tumor tissues,as well as inhibition of CD4+T,Treg,and DC cell infiltration within the spleen in the drug administration group.Additionally,the tumor volume analysis indicated that the drug administra-tion group effectively inhibited tumor growth.The flow results illustrate that the group administering treatment exhibited significant increases in CD8+T cell expression levels in tumor tissue and DC cells in the spleen.Furthermore,the treatment effec-tively inhibited the infiltration of CD4+T and Treg cells.The results also indicate that the treatment significantly reduced tumor growth,with the tumor inhibition rate being better with PD-L1 antibody alone than with the SFI group.Additionally,combin-ing drugs resulted in superior results compared to the PD-L1 antibody group alone.CONCLUSION:SFI combined with a PD-L1 antibody can have synergis-tic anti-tumor effects,potentially enhancing DC cell infiltration and promoting T cell activation.Immu-nohistochemistry results indicate a positive impact on the tumor immune microenvironment.
4.Application of phase angle in evaluating nutritional status of peritoneal dialysis patients
Jialu ZHUO ; Ning YANG ; Zhihua QU ; Yuehua ZHANG ; Ting HAN
China Modern Doctor 2024;62(20):57-62
Objective To analyze the value of phase angle(PA)measured by bioelectrical impedance analysis in evaluating nutritional status of peritoneal dialysis(PD)patients.Methods Totally 271 patients admitted to the Department of Nephrology,Tenth People's Hospital Affiliated to Tongji University from April 2020 to December 2021 were selected.InBody S10(Korean Biospace)was used to detect PA at 50kHz,which was divided into normal PA group and low PA group.The differences of general data and laboratory indexes between the two groups were compared,and the relationship between PA and each index was analyzed by Pearson correlation analysis and multiple linear regression analysis.Results Among 271 PD patients,108(39.9%)were in the normal PA group and 163(60.1%)were in the low PA group.The proportion of diabetic nephropathy patients in low PA group was significantly higher than that in normal PA group.Pearson correlation analysis showed that PA was negatively correlated with age,glycated hemoglobin,neutrophil to lymphocyte ratio(NLR),percent body fat(PBF),edema index and visceral fat area(VFA).It was positively correlated with creatinine,prealbumin,albumin,predictive nutritional index(PNI),25-hydroxyvitamin D3[25(OH)D3],serum iron,fat free mass,skeletal muscle mass,arm muscle circumference(AMC),bone mineral content,VFA,basal metabolic rate and skeletal muscle mass index(SMI)(P<0.05).Multiple linear regression analysis showed that creatinine,NLR,AMC,SMI were independently correlated with PA.Conclusions Bioelectrical impedance analysis(BIA)is non-invasive and rapid to evaluate the nutritional status of patients.Early identification of patients'nutritional status and implementation of individualised nutritional interventions are important ways to improve the quality of life and survival of patients with renal failure.
5.Robotic urologic surgery using the KangDuo-Surgical Robot-01 system: A single-center prospective analysis.
Shengwei XIONG ; Shubo FAN ; Silu CHEN ; Xiang WANG ; Guanpeng HAN ; Zhihua LI ; Wei ZUO ; Zhenyu LI ; Kunlin YANG ; Zhongyuan ZHANG ; Cheng SHEN ; Liqun ZHOU ; Xuesong LI
Chinese Medical Journal 2023;136(24):2960-2966
BACKGROUND:
The KangDuo-Surgical Robot-01 (KD-SR-01) system is a new surgical robot recently developed in China. The aim of this study was to present our single-center experience and mid-term outcomes of urological procedures using the KD-SR-01 system.
METHODS:
From August 2020 to April 2023, consecutive urologic procedures were performed at Peking University First Hospital using the KD-SR-01 system. The clinical features, perioperative data, and follow-up outcomes were prospectively collected and analyzed.
RESULTS:
A total of 110 consecutive patients were recruited. Among these patients, 28 underwent partial nephrectomy (PN), 41 underwent urinary tract reconstruction (26 underwent pyeloplasty, 3 underwent ureteral reconstruction and 12 underwent ureterovesical reimplantation [UR]), and 41 underwent radical prostatectomy (RP). The median operative time for PN was 112.5 min, 157.0 min for pyeloplasty, 151.0 min for ureteral reconstruction, 142.5 min for UR, and 138.0 min for RP. The median intraoperative blood loss was 10 mL for PN, 10 mL for pyeloplasty, 30 mL for ureteral reconstruction, 20 mL for UR, and 50 mL for RP. All procedures were successfully completed without conversion, and there were no major complications in any patient. The median warm ischemia time of PN was 17.3 min, and positive surgical margin was not noted in any patient. The overall positive surgical margin rate of RP was 39% (16/41), and no biochemical recurrence was observed in any RP patient during the median follow-up of 11.0 months. The surgical success rates of pyeloplasty and UR were 96% (25/26) and 92% (11/12) during the median follow-up of 29.5 months and 11.5 months, respectively.
CONCLUSION
The KD-SR-01 system appears feasible, safe, and effective for most urological procedures, based on our single-center experience.
Male
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Humans
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Robotic Surgical Procedures/methods*
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Robotics
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Treatment Outcome
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Retrospective Studies
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Ureter/surgery*
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Urologic Surgical Procedures/methods*
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Laparoscopy/methods*
6.Association of normal weight obesity with carotid atherosclerosis and peripheral arterial stiffness
Hong GONG ; Tuo HAN ; Qian WANG ; Meng GUO ; Zhihua ZHOU ; Jieqiong ZHAO ; Lixia WANG ; Yiwen WANG ; Congxia WANG
Journal of Xi'an Jiaotong University(Medical Sciences) 2022;43(3):343-347
【Objective】 To investigate the association of normal weight obesity (NWO) with carotid atherosclerosis (CAS) and peripheral arterial stiffness (PAS) in persons received physical examination. 【Methods】 A total of 1 894 people with normal BMI (18.5-23.9 kg/m2) were consecutively enrolled for this study. All these people had completed body fat measurement, carotid artery ultrasound examination and peripheral arterial stiffness detection. Then they were divided into control group, CAS group, PAS group, and CAS + PAS group according to the test results mentioned above. Clinical data were compared between different groups to assess the baseline situation. Besides, Multivariate Logistic regression analysis was performed to determine independent risk factors for atherosclerosis. 【Results】 The proportion of NWO in CAS group, PAS group, and CAS + PAS group was significantly higher than that in normal group (P<0.05). Univariate analysis results showed that NWO was correlated with greater risks of both CAS and PAS (P<0.05). However, multiple factors analysis suggested that NWO was not associated with PAS, but with CAS (OR=1.286, 95% CI: 1.032-1.603, P<0.05). 【Conclusion】 NWO is closely related to the occurrence of CAS and may be an independent risk factor for CAS. Attention should be paid to the body fat mass of the NWO population. Early intervention is needed to prevent the occurrence of CAS in these people.
7.Gongji classification and treatment strategies for lateral clavicle fractures
Jianhong WU ; Jingming DONG ; Zhihua HAN ; Zhongguo FU ; Ming XIANG ; Weidong NI ; Lei ZHANG ; Xiaoming WU
Chinese Journal of Orthopaedics 2022;42(4):220-227
Objective:To establish a new classification of lateral clavicle fractures and to evaluate its clinical value.Methods:The data of 67 patients with lateral clavicle fractures admitted from January 2016 to December 2020 were included. Thirty-seven cases were from Shanghai First People's Hospital, including 22 males and 15 females, with an average age of 49.1 years (22-78 years). Thirty cases were from the Second Upper Limb Ward of Tianjin Hospital of Tianjin, including 20 males and 10 females, with an average age of 47.6 years (19-76 years). The ligament injury was determined by measuring the coracoclavicular space on Zanca view X-ray and the distance between the fracture fragment on the inferior surface of the 3D-CT and the distal end of the clavicle. All patients were classified according to the new classification (based on the measurement on Zanca view X-ray and 3D-CT reconstruction, the relationship between the fracture and the coracoclavicular ligament footprint, coracoclavicular ligament injury, the injury of the acromioclavicular joint and the stability of the fracture), conservative treatment is preferable for stable fractures, and surgical treatment for unstable fractures. Three experienced orthopaedic surgeons and three radiologists independently observed the imaging data of 67 patients with distal clavicle fractures, determined the fracture type according to the new classification, and randomly reclassified after 4 weeks interval. Finally, 15 cases were randomly selected for internal control (2 junior orthopedic physicians), and the ICC value was used to assess the reliability. Results:The lateral clavicle fractures were divided into 5 types according to the Gongji classification. Type 1: isolated conical tubercle avulsion fracture, and the fracture line is located medial to the coracoid process; Type 2: complete involvement of the trapezoid & conical ligament at the clavicle insertion, and the fracture line extends to the middle of the clavicle, mean while the acromioclavicular joint is intact; Type 3: fracture fragments on the inferior surface involving the trapezoidal/conical ligament, respectively; Type 4: rupture of the conical ligament, and avulsion fracture of the trapezoid ligament; Type 5: conical ligament intact, and avulsion fracture of clavicle insertion of the trapezoid ligament. There were 18 cases of type 1, 4 cases of type 2, 8 cases of type 3, 32 cases of type 4, and 5 cases of type 5. The inter-observer and intra-observer agreement of all included cases was good (inter-group: first ICC=0.764, second ICC=0.778; intra-group: shoulder specialist ICC=0.782, radiologist ICC=0.750, internal control ICC=0.793). Types 1 and 2 fractures were fixed with anatomical plate and coracoid anchor. Type 3 and 4 fractures were fixed with clavicle hook plate and coracoid anchor. And type 5 underwent conservative treatment. At the last follow-up, all patients had no obvious shoulder joint instability and pain, and no internal fixation failure or fixation breakage was found. Conclusion:The Gongji classification has moderate reliability between observers and intra-observers, and the Gongji distal clavicle fracture classification has a good significance for evaluating the stability of the fracture and guiding the selection of the treatment.
8.Application and clinical evaluation of ultrasound-guided biliary drainage tube replacement technology
Anhong ZHANG ; Ruixin ZHANG ; Jie MA ; Bo QIU ; Xin YI ; Zhihua LU ; Lijie ZHENG ; Hanguang DONG ; Tian HAN ; Li ZHANG ; Yuanhui JIANG ; Jun XU
Journal of Clinical Hepatology 2022;38(11):2542-2545
Objective To summarize the preliminary application results of ultrasound-guided biliary drainage tube replacement, present the corresponding technical points, and discuss the operation strategy and clinical application value. Methods The clinical data of 60 patients who underwent ultrasound-guided biliary drainage tube replacement in Qilu Hospital of Shandong University between August 2014 and August 2020 were retrospectively analyzed. The operation procedure, clinical applications, and postoperative complications were summarized and analyzed. Results Fifty-eight of the 60 patients (96.67%) were successfully replaced with drainage tubes along the original sinus. Among them, dilated sinus tracts of 47 patients were placed with coarse-grade drainage tubes, and dilated sinus tracts of the remaining 11 patients were placed with the original type of drainage tubes, with the mean operation time of 15.8(12.0-19.0) min under local anesthesia. In total, bile was drained from 28 patients receiving PTCD drainage, 23 patients receiving gallbladder drainage, and 9 patients receiving T-tube drainage. The post-operation evaluation revealed that the drainage situation has improved, with a 100% effective rate. No obvious abnormality was found in the postoperative follow-up visit. Conclusion The replacement of drainage tube under ultrasound guidance is simple, safe and feasible, and it provides further promotion in clinical practice with sufficient data support.
9.External apical root resorption in orthodontic tooth movement: the risk factors and clinical suggestions from experts' consensus.
Huang LI ; Xiuping WU ; Lan HUANG ; Xiaomei XU ; Na KANG ; Xianglong HAN ; Yu LI ; Ning ZHAO ; Lingyong JIANG ; Xianju XIE ; Jie GUO ; Zhihua LI ; Shuixue MO ; Chufeng LIU ; Jiangtian HU ; Jiejun SHI ; Meng CAO ; Wei HU ; Yang CAO ; Jinlin SONG ; Xuna TANG ; Ding BAI
West China Journal of Stomatology 2022;40(6):629-637
External apical root resorption is among the most common risks of orthodontic treatment, and it cannot be completely avoided and predicted. Risk factors causing orthodontic root resorption can generally be divided into patient- and treatment-related factors. Root resorption that occurs during orthodontic treatment is usually detected by radiographical examination. Mild or moderate root absorption usually does no obvious harm, but close attention is required. When severe root resorption occurs, it is generally recommended to suspend the treatment for 3 months for the cementum to be restored. To unify the risk factors of orthodontic root resorption and its clinical suggestions, we summarized the theoretical knowledge and clinical experience of more than 20 authoritative experts in orthodontics and related fields in China. After discussion and summarization, this consensus was made to provide reference for orthodontic clinical practice.
Humans
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Tooth Movement Techniques/adverse effects*
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Root Resorption/etiology*
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Consensus
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Dental Cementum
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Risk Factors
10.Analysis of the Marketing Approval of Pediatric Drugs in the United States and Its Enlightenment to Pedia tric Drug Use Guarantee in China
Yajun WANG ; Rong HAN ; Zhihua YUE ; Xinwen XU ; Zhigang ZHAO
China Pharmacy 2021;32(2):133-138
OBJECTIVE:To provide sugge stions for improving the variety of pediatric drugs and ensuring the safety of pediatric drug use in China. METHODS :The historical evolution of laws and regulations on the marketing approval of pediatric drugs in the United States and the implementation results of relevant policies were summarized. Combined with the current situation of the development of pediatric drugs in China ,some suggestions were put forward to ensure the accessibility and safety of pediatric drug use in China. RESULTS & CONCLUSIONS :Since 1994,the United States had issued a series of laws and regulations to encourage the development of pediatric drugs. At present ,the marketing approval of pediatric drugs were mainly based on the two laws of Best Pediatric Drug Act(BPCA)and Pediatric Research Equality Act (PREA). From 1998 to 2019,the amount of supplements of pediatric drug information in drug instructions of the United States showed a fluctuating growth. As of April 2020,854 kinds of drugs had been modified in pediatric instructions ,792 of which had been carried out post marketing pediatric clinical research ,and the problem of incomplete pediatric instructions had also been greatly improved. At present ,China’s policies on pediatric drugs mainly included encouraging R&D innovation ,giving priority to review and approval ,and strengthening R&D technical guidance. Although certain achievements had been made ,there were still some problems ,such as imperfect policies and regulations ,and great difficulties carrying out pediatric drug clinical trials. It is suggested that our country should draw lessons from the American regulations on pediatric drugs ,pediatric research and the catalogue of pediatric drugs ,and establish a system and catalogue of ped iatric drug use suitable for China ’s national conditions ,so as to improve the effectiveness ,safety and accessibilityof pediatric drugs.

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