1.Effect and mechanism of Prunus mume against hepatic fibrosis
Feng HAO ; Ji LI ; Jing DU ; Yuchen OUYANG ; Yichun CUI ; Shuang WEI
China Pharmacy 2025;36(2):172-178
OBJECTIVE To explore the effect and mechanism of Prunus mume against hepatic fibrosis (HF). METHODS Male SD rats were randomly divided into normal control group (n=10) and modeling group (n=50). The modeling group established HF model using carbon tetrachloride. The modeled rats were randomly divided into model group (normal saline), positive control group [colchicine, 0.09 mg/(kg·d)], and P. mume low-dose, medium-dose and high-dose groups [1.35, 2.70, 5.40 g/(kg·d)], with 9 rats in each group. They were given the corresponding drug/normal saline intragastrically, once a day, for 8 consecutive weeks. After the last medication, the liver index was calculated, while liver function indexes, liver fiber indexes, oxidative stress indicators and inflammatory factors of rats were measured. HE staining was used to observe the pathological changes in liver tissue of rats; Masson staining was used to observe the degree of HF in liver tissue of rats; transmission electron microscopy was used to observe the ultrastructure of liver tissue in rats; TUNEL staining was used to detect liver cell apoptosis in each group of rats. Western blot method was used to detect the protein expressions of transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) in liver tissue of rats. RESULTS Compared with normal control group, the levels of alanine transaminase, alkaline phosphatase, aspartate transaminase, total bilirubin, malondialdehyde, procollagen type Ⅲ protein, Ⅳ-type pre collagenase, laminin, hyaluronic acid, interleukin-6, tumor necrosis factor-α, as well as the protein expressions of TGF-β1 and PDGF in model group were increased significantly, while the levels of superoxide dismutase and glutathione peroxidase were significantly reduced (P<0.01); the HE, Masson staining and transmission electron microscopy observation results showed obvious HF characteristics in rats of model group. Compared with model group, varying degrees of improvement in above indexes were observed in P. mume groups, and the above 2021BSZR011) indicators of rats in P. mume medium-dose and high-dose groups were reversed significantly (P<0.05 or P<0.01). CONCLUSIONS P. mume has an anti-HF effect, which may be achieved through mechanisms such as antioxidation, anti-inflammation, reduction of collagen production, inhibition of PDGF protein expression, and regulation of TGF- β1 signaling pathway.
2.Effect and mechanism of Prunus mume against hepatic fibrosis
Feng HAO ; Ji LI ; Jing DU ; Yuchen OUYANG ; Yichun CUI ; Shuang WEI
China Pharmacy 2025;36(2):172-178
OBJECTIVE To explore the effect and mechanism of Prunus mume against hepatic fibrosis (HF). METHODS Male SD rats were randomly divided into normal control group (n=10) and modeling group (n=50). The modeling group established HF model using carbon tetrachloride. The modeled rats were randomly divided into model group (normal saline), positive control group [colchicine, 0.09 mg/(kg·d)], and P. mume low-dose, medium-dose and high-dose groups [1.35, 2.70, 5.40 g/(kg·d)], with 9 rats in each group. They were given the corresponding drug/normal saline intragastrically, once a day, for 8 consecutive weeks. After the last medication, the liver index was calculated, while liver function indexes, liver fiber indexes, oxidative stress indicators and inflammatory factors of rats were measured. HE staining was used to observe the pathological changes in liver tissue of rats; Masson staining was used to observe the degree of HF in liver tissue of rats; transmission electron microscopy was used to observe the ultrastructure of liver tissue in rats; TUNEL staining was used to detect liver cell apoptosis in each group of rats. Western blot method was used to detect the protein expressions of transforming growth factor-β1 (TGF-β1) and platelet-derived growth factor (PDGF) in liver tissue of rats. RESULTS Compared with normal control group, the levels of alanine transaminase, alkaline phosphatase, aspartate transaminase, total bilirubin, malondialdehyde, procollagen type Ⅲ protein, Ⅳ-type pre collagenase, laminin, hyaluronic acid, interleukin-6, tumor necrosis factor-α, as well as the protein expressions of TGF-β1 and PDGF in model group were increased significantly, while the levels of superoxide dismutase and glutathione peroxidase were significantly reduced (P<0.01); the HE, Masson staining and transmission electron microscopy observation results showed obvious HF characteristics in rats of model group. Compared with model group, varying degrees of improvement in above indexes were observed in P. mume groups, and the above 2021BSZR011) indicators of rats in P. mume medium-dose and high-dose groups were reversed significantly (P<0.05 or P<0.01). CONCLUSIONS P. mume has an anti-HF effect, which may be achieved through mechanisms such as antioxidation, anti-inflammation, reduction of collagen production, inhibition of PDGF protein expression, and regulation of TGF- β1 signaling pathway.
3.Efficacy and Safety Analysis of Drug-coated Balloon in the Treatment of De Novo Coronary Chronic Total Occlusion Lesions
Rong LIU ; Shubin QIAO ; Jingang CUI ; Hao GUAN ; Haobo XU ; Jing LIU ; Changdong GUAN
Chinese Circulation Journal 2024;39(2):123-126
Objectives:To evaluate the efficacy and safety of drug-coated balloon in the treatment of de novo coronary chronic occlusive lesions. Methods:Consecutive patients with de novo coronary chronic occlusive lesions treated with drug-coated balloons only were included in this study.The general information,medical history,and surgical information of the patients were recorded,and major adverse cardiovascular events(MACE,including cardiac death,myocardial infarction,and target vessel revascularization)were recorded by telephone or outpatient follow-up. Results:A total of 160 patients were included.There were 26 ostial lesions(16.3%),42 bifurcated lesions(26.3%),117 diffuse lesions(73.1%),and 87 calcified lesions(54.4%).The reference vessel diameter was(2.3±0.4)mm.During hospitalization,there were no acute myocardial infarction,cardiac death,target lesion revascularization,or acute coronary thrombosis.Cardiac death occurred in 1 case and target vessel revascularization occurred in 6 cases during follow-up.The MACE rate is 4.4%. Conclusions:Drug balloon therapy for de novo coronary chronic occlusive lesions is safe and effective,and the prognosis is satisfactory.
4.Comparative analysis of domestic Octoparms and imported Celect inferior vena cava filter in interventional treatment of venous thromboembolism
Jinchang XIAO ; Qianxin HUANG ; Jing YANG ; Mingming JIANG ; Ning WEI ; Hongtao LIU ; Yanfeng CUI ; Yuming GU ; Maoheng ZU ; Hao XU ; Qingqiao ZHANG
Journal of Practical Radiology 2024;40(3):456-459,463
Objective To compare and analyze the application value of domestic Octoparms and imported Celect inferior vena cava filter(IVCF)in the interventional treatment of venous thromboembolism(VTE).Methods Forty patients with VTE were randomly divided into Octoparms group(experimental group)and Celect group(control group)according to the double-blinded method of the central random system.All the patients underwent filter placement,catheter-directed thrombolysis and filter retrieval.The primary end point was the success of filter placement and retrieval,and the secondary end point included indwelling complications such as the occurrence of pulmonary embolism(PE)and filter tilt and migration.Results Forty patients were enrolled in this study,22 patients and 18 patients were divided into the experimental group and the control group,respectively.Among them,11 cases were identified with right lower extremity deep vein thrombosis,29 cases with left lower extremity deep vein thrombosis,17 cases with PE,and 6 cases with inferior vena cava thrombosis.The success rate of IVCF placement was 100%in all participants.Immediately after filter place-ment,the angle of filter tilt was(3.8±2.3)° in the experimental group and(4.9±2.8)° in the control group(t=1.44,P=0.16).Filter retrieval was successful in 21 cases(21/22,95.5%)of the experimental group and 17 cases(17/18,95.5%)of the control group.There was no significant difference between the two groups(t=0.14,P=0.89).The mean indwelling time of filter was(8.0±2.1)days in the experimental group and(9.7±3.1)days in the control group(t=0.73,P=0.47).The angle of filter tilt was(5.3±3.4)° in the experimental group and(5.7±7.7)° in the control group(t=0.19,P=0.85).There was no significant difference for filter placement and retrieval between the two groups(t=0.48 and 2.00,P=0.06 and 0.64,respectively).There were no complications of filter migration,strut penetration or new PE in both groups.Conclusion The application value of domestic Octoparms and impor-ted Celect IVCF is similar in interventional treatment of VTE.
5.Pathway analysis of the impact of family environment and community services on the care needs of disabled elderly people
Huanhuan DENG ; Xijun HAO ; Huiying CUI ; Xiaohua TIAN ; Jing LI ; Chaozheng LI ; Quanrong GUO
Chinese Journal of Practical Nursing 2024;40(10):752-758
Objective:To understand the current situation of care needs for disabled elderly people, analyze the impact of the family environment and community services on the care needs and care pathways of older people with disabilities and to formulate effective interventions.Methods:A cross-sectional survey was conducted from August 2022 to March 2023 in five tertiary-level hospitals in Tangshan city. The survey included 332 elderly people who were disabled before hospitalization and their primary caregivers, who were selected using a convenience sampling method. The survey investigated their general information, degree of disability, family members′ support, children′s filial piety and old age ethical level, family relationships, and the care needs of the elderly people who were disabled. SPSS 22.0 was used for one-way and correlation analyses as well as multiple linear regression analyses, and AMOS 22.0 was used for the development of structural equations for path analysis.Results:Among 332 disabled elderly individuals, there were 166 males and 166 females each. The care needs score for elderly people with disabilities was 101.54 ± 16.38. The care needs of this population can be influenced by several factors, including the level of disability, number of chronic conditions, presence of chronic pain, filial piety and old age ethical level of caregivers, family relationships, and the availability of care services in the community or village. These factors had direct effects of 0.468, 0.155, -0.083, -0.350, -0.094, and 0.104, respectively.Chronic diseases and chronic pain indirectly affected the demand for care through the degree of incapacity (with respective indirect effect values of 0.065 and 0.049). Additionally, the demand for care was indirectly influenced by the level of filial piety and ethics of the caregiver through the degree of incapacity and the family relationships (an indirect effect value of -0.162).Conclusions:The care needs of the disabled elderly are high, and the personal physiology, family environment and community support of the disabled elderly will directly or indirectly affect their care needs. Therefore, many factors should be considered comprehensively considered to improve the quality of care of the disabled elderly.
6.Antimicrobial resistance analysis and genomic characteristics of enteropathogenic Escherichia coli derived from ducks
Jun-Lin LI ; Jia-Meng HU ; Luo WANG ; Jia-Rui LI ; Hao-Tian LIU ; Jing XIA ; Min CUI ; Li-Kou ZOU ; Xin-Feng HAN
Chinese Journal of Zoonoses 2024;40(8):701-707
Enteropathogenic Escherichia coli(EPEC),a zoonotic foodborne pathogen,can induce severe and prolonged di-arrhea,thus substantially affecting global public health safety.To understand the pathogenicity of EPEC and its potential risk to human health,this study investigated the antimicrobial resistance and genome-wide characteristics of EPEC originating from ducks.After identification of EPEC with the plate method and PCR,antimicrobial susceptibility of the isolates was examined with the microbroth dilution method.In addition,analyses of serotype,sequence type(ST),and plasmid incompatibility groups were conducted with whole-genome sequencing(WGS)and bioinformatic methods.Ten EPEC isolates were identified,including serotypes O71∶H40 and O3∶H21.All EPEC strains exhibited multiple drug resistance.The highest proportion of resistance(100%)was observed to ciprofloxacin,streptomycin,tetracycline,and polymyxin B.In contrast,the isolates showed susceptibility to cefoxitin,amikacin,and imipenem.Furthermore,all strains carried the tetracycline resistance gene tet(A)and extended-spectrum β-lactamase(ESBL)resistance genes,including blaOXA-10,blaTEM-1A,and blaTEM-1B.Various virulence genes,associated primarily with the secretory system,were de-tected in the isolates.However,no bf p genes or per ARC genes were identified,thus indicating that the EPEC isolates were atypical EPEC(aEPEC).The results demonstrated the presence of multiple antimicrobial resistance,multiple resistance and viru-lence genes,and various plasmid incompatibility groups,thus in-dicating potential pathogenicity to humans.Strengthened monitoring of duck-derived EPEC is crucial to effectively control the spread of the pathogen and safeguard public health.
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.Yinlai Decoction Protects Microstructure of Colon and Regulates Serum Level of D-Lactic Acid in Pneumonia Mice Fed with High-Calorie and High-Protein Diet.
Yun-Hui WANG ; He YU ; Tie-Gang LIU ; Teck Chuan KONG ; Zi-An ZHENG ; Yu-Xiang WAN ; Chen BAI ; Yu HAO ; Ying-Qiu MAO ; Jun WU ; Jing-Nan XU ; Li-Jun CUI ; Yu-Han WANG ; Yan-Ran SHAN ; Ying-Jun SHAO ; Xiao-Hong GU
Chinese journal of integrative medicine 2023;29(8):714-720
OBJECTIVE:
To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD).
METHODS:
Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice.
RESULTS:
The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05).
CONCLUSIONS
YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.
Mice
;
Male
;
Animals
;
Lactic Acid/pharmacology*
;
Intestinal Mucosa
;
Colon/pathology*
;
Dexamethasone/pharmacology*
;
Diet, High-Protein
;
Pneumonia/pathology*
9.Mechanisms of PiT2-loop7 Missense Mutations Induced Pi Dyshomeostasis.
Hao SUN ; Xuan XU ; Junyu LUO ; Tingbin MA ; Jiaming CUI ; Mugen LIU ; Bo XIONG ; Shujia ZHU ; Jing-Yu LIU
Neuroscience Bulletin 2023;39(1):57-68
PiT2 is an inorganic phosphate (Pi) transporter whose mutations are linked to primary familial brain calcification (PFBC). PiT2 mainly consists of two ProDom (PD) domains and a large intracellular loop region (loop7). The PD domains are crucial for the Pi transport, but the role of PiT2-loop7 remains unclear. In PFBC patients, mutations in PiT2-loop7 are mainly nonsense or frameshift mutations that probably cause PFBC due to C-PD1131 deletion. To date, six missense mutations have been identified in PiT2-loop7; however, the mechanisms by which these mutations cause PFBC are poorly understood. Here, we found that the p.T390A and p.S434W mutations in PiT2-loop7 decreased the Pi transport activity and cell surface levels of PiT2. Furthermore, we showed that these two mutations attenuated its membrane localization by affecting adenosine monophosphate-activated protein kinase (AMPK)- or protein kinase B (AKT)-mediated PiT2 phosphorylation. In contrast, the p.S121C and p.S601W mutations in the PD domains did not affect PiT2 phosphorylation but rather impaired its substrate-binding abilities. These results suggested that missense mutations in PiT2-loop7 can cause Pi dyshomeostasis by affecting the phosphorylation-regulated cell-surface localization of PiT2. This study helps understand the pathogenesis of PFBC caused by PiT2-loop7 missense mutations and indicates that increasing the phosphorylation levels of PiT2-loop7 could be a promising strategy for developing PFBC therapies.
Humans
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Cell Membrane
;
Mutation, Missense
;
Phosphates/metabolism*
;
Sodium-Phosphate Cotransporter Proteins, Type III/genetics*
10.Investigation on the cognition and training status of basic life support among county medical staff in Linfen, Shanxi Province
Li MA ; Jing WU ; Kang ZHENG ; Lanfang DU ; Qingbian MA ; Ruifang LEI ; Xiaoling CUI ; Xinmei HAO
Chinese Journal of Emergency Medicine 2023;32(1):126-130
Objective:To understand the cognition and training status of basic life support among medical staff in Linfen, Shanxi Province, and to provide reference for the development of targeted training strategies and programs.Methods:A questionnaire survey was conducted among medical staff in 12 county hospitals in Linfen, Shanxi Province by convenience sampling method. The survey included the general characteristics of departments and medical staff, previous basic life support training assessment and cognitive status.Results:A total of 839 medical staff were included, 756 (90.1%) completed the survey, 183 (24.2%) were doctors and 573 (75.8%) were nurses. Most personnel lacked awareness of environmental safety, emergency response system start-up, adequate compression, airway management, and electrical defibrillation.Conclusions:The cognitive status of basic life support of medical staff in Linfen county is not optimistic. It is necessary to construct an applicable precision training course and retraining assessment system to improve the cognitive level and practical operation ability.

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