1.DNAzyme targeting RIP3 suppresses NLRP3-mediated necroinflammation for the treatment of inflammatory diseases.
Jiaxin JIA ; Hugang ZHANG ; Guangxu FANG ; Yang LI ; Kai WEN ; Hanyu LIU ; Haobo HAN ; Quanshun LI
Acta Pharmaceutica Sinica B 2025;15(11):5908-5932
Necroptosis, a form of programmed cell death, initiates a series of biological responses and further culminates in necroinflammatory processes, consequently limiting the efficacy of cytokine antagonists in treating inflammatory diseases. To address this issue, DNAzyme R3-Dz specifically targeting receptor-interacting protein kinase 3 (RIP3) mRNA, a necrosome component, has been successfully developed and studied to elucidate the mechanism in cleaving its target mRNA. Then a polyamidoamine (PAMAM) derivative was constructed through the modification of nucleobase analog (termed AP) to achieve the R3-Dz delivery to macrophages. The AP/R3-Dz nanoparticles effectively downregulated the RIP3 expression, leading to subsequent decrease in the levels of reactive oxygen species (ROS) and damage-associated molecular patterns (DAMPs), ultimately inhibiting the necroinflammatory processes mediated by the NOD-like receptor family pyrin domain-containing 3 (NLRP3). Finally, AP/R3-Dz nanoparticles and their combination with the NLRP3 inhibitor MCC950 suppressed the necrotic phenotype and ameliorated the disease progression in diverse models, including gouty arthritis, autoimmune hepatitis and rheumatoid arthritis. In summary, the AP/R3-Dz nanoparticles in combination with MCC950 have been demonstrated to achieve the intervention in necroptosis and inflammation by dual disruption of the intricate feedback loop of necroinflammation and thus have promising potential in the treatment of inflammatory diseases.
2.Epidemiological characteristics of febrile seizure among children under 6 years old in Ningbo City from 2015 to 2021
Guangxu LIU ; Liang ZHANG ; Houyu ZHAO ; Siwei DENG ; Junting YANG ; Ning LI ; Rui MA ; Yan HE ; Guozhang XU ; Zhike LIU ; Siyan ZHAN
Journal of Peking University(Health Sciences) 2025;57(3):584-591
Objective:To describe the epidemiological characteristics and changes of febrile seizure(FS)among children under 6 years old in Ningbo City,Zhejiang Province from 2015 to 2021.Methods:Based on the Ningbo Regional Health Information Platform,a dynamic cohort was established using vacci-nation registration information,and the cases of FS were identified by the diagnostic results of Chinese terms or International Classification of Diseases 10th revision(ICD-10)R56.0 code in the electronic medical records.The first visit of FS during the observation period was defined as a new case,and a re-currence case was defined as the case with a visit interval of more than 7 days.The 95%confidence in-terval(CI)of FS incidence density was calculated by the Poisson distribution.Results:From January 2015 to June 2020,there were 1.3 million children under 6 years old in Ningbo,with male accounting for 52.87%.The median follow-up time was 2.83(1.55-4.00)years.During the follow-up period,12 776 new onset cases had FS,with more males than females,with an overall incidence density of 4.34(95%CI:4.27-4.40)/1 000 person-years and a recurrence rate of 21.63%.There was a higher inci-dence density in children who were male,born in Ningbo and of non-mobility.The incidence density of FS was higher in urban areas than in rural and rural-urban fringe areas,and the incidence density was different among districts and counties.The peak density was found in children aged 18-23 months[8.42(95%CI:8.11-8.74)/1 000 person-years].From 2015 to 2019,the incidence density in-creased with calendar year(Ptrend<0.001),and the highest was 5.62(95%CI:5.43-5.81)/1 000 person-years.The incidence density of FS decreased significantly during the period between 2020 and 2021.The incidence density was higher in winter.Conclusion:From 2015 to 2019,the overall inci-dence density of FS in children under 6 years old in Ningbo City presented an increasing trend.More at-tention should be paid to the health education,the improvement of the health maintenance model,the en-hancement of the cognition of FS,the identification and treatment of FS among high-risk population and regions so as to prevent its recurrence and reduce the disease burden during the corona virus disease 2019(COVID-19)epide-mic.
3.Effect of high-frequency repetitive transcranial magnetic stimulation on upper limb function of stroke patients based on motor sequence learning
Wanting SUN ; Ailipinai YASEN ; Xiang GONG ; Yue XIAO ; Zhaodan GAN ; Mingjie LIU ; Lanting ZENG ; Shuyue MA ; Jun LU ; Guangxu XU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(7):812-821
Objective To investigate the effects of high-frequency repetitive transcranial magnetic stimulation(HF-rTMS)applied to the supplementary motor area(SMA)or primary motor cortex(M1)on upper limb function in stroke patients in terms of motor sequence learning.Methods From April,2024 to February,2025,60 inpatients were recruited from the First Affiliated Hospital with Nan-jing Medical University.They were randomly assigned into the control group,SMA group and M1 group,with 20 patients in each group.All the groups received medication and conventional rehabilitation.On this basis,SMA group underwent HF-rTMS on the affected side's SMA,while M1 group received HF-rTMS on the affected side's M1 for two weeks.All the groups were measured with motor evoked potentials(MEP),the serial reaction time(RT)task,Fugl-Meyer Assessment-Upper Extremities(FMA-UE)and modified Barthel Index(MBI)before and after intervention.Results The SMA and M1 groups dropped one case respectively.MEP elicitation rate of the affected side's increased in SMA and M1 groups(P<0.05),and it was better than that in the control group(χ2>4.792,P<0.05).The intra-group effects of RTsequential sequence,FMA-UE and MBI scores were significant(|F|>81.546,P<0.05).The inter-group effects of RTrandom sequence,RTsequential sequence,?RT,and MBI scores were significant(F>3.228,P<0.05).The in-teractive effects of RTrandom sequence,RTsequential sequence,?RT,FMA-UE and MBI scores were significant(|F|>3.520,P>0.05).After intervention,RTsequential sequence,?RT,FMA-UE and MBI scores improved(P<0.05).RTrandom sequence was lower in SMA group than in the control group(P<0.017),RTsequential sequence,?RT,FMA-UE and MBI scores im-proved more in SMA and M1 groups than in the control group(P<0.05),but no significant difference was found between the SMA group and the M1 group(P>0.05).Conclusion HF-rTMS applied to the affected SMA or M1 can activate motor sequence learning and promote the recov-ery of upper limb function in stroke patients.
4.Structure, content and data standardization of rehabilitation medical records
Yaru YANG ; Zhuoying QIU ; Di CHEN ; Zhongyan WANG ; Meng ZHANG ; Shiyong WU ; Yaoguang ZHANG ; Xiaoxie LIU ; Yanyan YANG ; Bin ZENG ; Mouwang ZHOU ; Yuxiao XIE ; Guangxu XU ; Jiejiao ZHENG ; Mingsheng ZHANG ; Xiangming YE ; Jian YANG ; Na AN ; Yuanjun DONG ; Xiaojia XIN ; Xiangxia REN ; Ye LIU ; Yifan TIAN
Chinese Journal of Rehabilitation Theory and Practice 2025;31(1):21-32
ObjectiveTo elucidate the critical role of rehabilitation medical records (including electronic records) in rehabilitation medicine's clinical practice and management, comprehensively analyzed the structure, core content and data standards of rehabilitation medical records, to develop a standardized medical record data architecture and core dataset suitable for rehabilitation medicine and to explore the application of rehabilitation data in performance evaluation and payment. MethodsBased on the regulatory documents Basic Specifications for Medical Record Writing and Basic Specifications for Electronic Medical Records (Trial) issued by National Health Commission of China, and referencing the World Health Organization (WHO) Family of International Classifications (WHO-FICs) classifications, International Classification of Diseases (ICD-10/ICD-11), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Interventions (ICHI Beta-3), this study constructed the data architecture, core content and data standards for rehabilitation medical records. Furthermore, it explored the application of rehabilitation record summary sheets (home page) data in rehabilitation medical statistics and payment methods, including Diagnosis-related Groups (DRG), Diagnosis-Intervention Packet (DIP) and Case Mix Index. ResultsThis study proposed a systematic standard framework for rehabilitation medical records, covering key components such as patient demographics, rehabilitation diagnosis, functional assessment, rehabilitation treatment prescriptions, progress evaluations and discharge summaries. The research analyzed the systematic application methods and data standards of ICD-10/ICD-11, ICF and ICHI Beta-3 in the fields of medical record terminology, coding and assessment. Constructing a standardized data structure and data standards for rehabilitation medical records can significantly improve the quality of data reporting based on the medical record summary sheet, thereby enhancing the quality control of rehabilitation services, effectively supporting the optimization of rehabilitation medical insurance payment mechanisms, and contributing to the establishment of rehabilitation medical performance evaluation and payment based on DRG and DIP. ConclusionStructured rehabilitation records and data standardization are crucial tools for quality control in rehabilitation. Systematically applying the three reference classifications of the WHO-FICs, and aligning with national medical record and electronic health record specifications, facilitate the development of a standardized rehabilitation record architecture and core dataset. Standardizing rehabilitation care pathways based on the ICF methodology, and developing ICF- and ICD-11-based rehabilitation assessment tools, auxiliary diagnostic and therapeutic systems, and supporting terminology and coding systems, can effectively enhance the quality of rehabilitation records and enable interoperability and sharing of rehabilitation data with other medical data, ultimately improving the quality and safety of rehabilitation services.
5.Standardization of electronic medical records data in rehabilitation
Yifan TIAN ; Fang XUN ; Haiyan YE ; Ye LIU ; Yingxin ZHANG ; Yaru YANG ; Zhongyan WANG ; Meng ZHANG ; Xiaoxie LIU ; Yanyan YANG ; Bin ZENG ; Mouwang ZHOU ; Yuxiao XIE ; Guangxu XU ; Jiejiao ZHENG ; Mingsheng ZHANG ; Xiangming YE ; Fubiao HUANG ; Qiuchen HUANG ; Yiji WANG ; Di CHEN ; Zhuoying QIU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(1):33-44
ObjectiveTo explore the data standard system of electronic medical records in the field of rehabilitation, focusing on the terminology and coding standards, data structure, and key content categories of rehabilitation electronic medical records. MethodsBased on the Administrative Norms for the Application of Electronic Medical Records issued by the National Health Commission of China, the electronic medical record standard architecture issued by the International Organization for Standardization and Health Level Seven (HL7), the framework of the World Health Organization Family of International Classifications (WHO-FICs), Basic Architecture and Data Standards of Electronic Medical Records, Basic Data Set of Electronic Medical Records, and Specifications for Sharing Documents of Electronic Medical Records, the study constructed and organized the data structure, content, and data standards of rehabilitation electronic medical records. ResultsThe data structure of rehabilitation electronic medical records should strictly follow the structure of electronic medical records, including four levels (clinical document, document section, data set and data element) and four major content areas (basic information, diagnostic information, intervention information and cost information). Rehabilitation electronic medical records further integrated information related to rehabilitation needs and characteristics, emphasizing rehabilitation treatment, into clinical information. By fully applying the WHO-FICs reference classifications, rehabilitation electronic medical records could establish a standardized framework, diagnostic criteria, functional description tools, coding tools and terminology index tools for the coding, indexing, functional description, and analysis and interpretation of diseases and health problems. The study elaborated on the data structure and content categories of rehabilitation electronic medical records in four major categories, refined the granularity of reporting rehabilitation content in electronic medical records, and provided detailed data reporting guidance for rehabilitation electronic medical records. ConclusionThe standardization of rehabilitation electronic medical records is significant for improving the quality of rehabilitation medical services and promoting the rehabilitation process of patients. The development of rehabilitation electronic medical records must be based on the national and international standards. Under the general electronic medical records data structure and standards, a rehabilitation electronic medical records data system should be constructed which incorporates core data such as disease diagnosis, functional description and assessment, and rehabilitation interventions. The standardized rehabilitation electronic medical records scheme constructed in this study can support the improvement of standardization of rehabilitation electronic medical records data information.
6.Standardization of outpatient medical record in rehabilitation setting
Ye LIU ; Qing QIN ; Haiyan YE ; Yifan TIAN ; Yingxin ZHANG ; Yaru YANG ; Zhongyan WANG ; Meng ZHANG ; Xiaoxie LIU ; Yanyan YANG ; Bin ZENG ; Mouwang ZHOU ; Yuxiao XIE ; Guangxu XU ; Jiejiao ZHENG ; Mingsheng ZHANG ; Xiangming YE ; Fubiao HUANG ; Qiuchen HUANG ; Yiji WANG ; Di CHEN ; Zhuoying QIU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(1):45-54
ObjectiveTo analyze the data structure and standards of rehabilitation outpatient medical records, to provide data support for improving the quality of rehabilitation outpatient care and developing medical insurance payment policies. MethodsBased on the normative documents issued by the National Health Commission, Basic Standards for Medical Record Writing and Standards for Electronic Medical Record Sharing Documents, in accordance with the Quality Management Regulations for Outpatient (Emergency) Diagnosis and Treatment Information Pages (Trial), reference to the framework of the World Health Organization Family of International Classifications (WHO-FICs), the data framework and content of rehabilitation outpatient medical records were determined, and the data standards were discussed. ResultsThis study constructed a data framework for rehabilitation outpatient medical records, including four main components: patient basic information, visit process information, diagnosis and treatment information, and cost information. Three major reference classifications of WHO-FICs, International Classification of Diseases, International Classification of Functioning, Disability and Health, and International Classification of Health Interventions,were used to establish diagnostic standards and standardized terminology, as well as coding disease diagnosis, functional description, functional assessment, and rehabilitation interventions, to improve the quality of data reporting, and level of quality control in rehabilitation. ConclusionThe structuring and standardization of rehabilitation outpatient medical records are the foundation for sharing of rehabilitation data. The using of the three major classifications of WHO-FICs is valuable for the terminology and coding of disease diagnosis, functional description and assessment, and intervention in rehabilitation outpatient medical records, which is significant for sharing and interconnectivity of rehabilitation outpatient data, as well as for optimizing the quality and safety of rehabilitation medical services.
7.Structure, content and data standardization of inpatient rehabilitation medical record summary sheet
Haiyan YE ; Qing QIN ; Ye LIU ; Yifan TIAN ; Yingxin ZHANG ; Yaru YANG ; Zhongyan WANG ; Meng ZHANG ; Xiaoxie LIU ; Yanyan YANG ; Bin ZENG ; Mouwang ZHOU ; Yuxiao XIE ; Guangxu XU ; Jiejiao ZHENG ; Mingsheng ZHANG ; Xiangming YE ; Fubiao HUANG ; Qiuchen HUANG ; Yiji WANG ; Di CHEN ; Zhuoying QIU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(1):55-66
ObjectiveTo explore the standardization of inpatient rehabilitation medical record summary sheet, encompassing its structure, content and data standards, to enhance the standardization level of inpatient rehabilitation medical record summary sheet, improve data reporting quality, and provide accurate data support for medical insurance payment, hospital performance evaluation, and rehabilitation discipline evaluation. MethodsBased on the relevant specifications of the National Health Commission's Basic Norms for Medical Record Writing, Specifications for Sharing Documents of Electronic Medical Records, and Quality Management and Control Indicators for Inpatient Medical Record Summary Sheet (2016 Edition), this study analyzed the structure and content of the inpatient rehabilitation medical record summary sheet. The study systematically applied the three major reference classifications of the World Health Organization Family of International Classifications, International Classification of Diseases (ICD-10/ICD-11, ICD-9-CM-3), International Classification of Functioning, Disability and Health (ICF), and International Classification of Health Interventions (ICHI Beta-3), for disease diagnosis, functional description and assessment, and rehabilitation intervention, forming a standardized terminology system and coding methods. ResultsThe inpatient rehabilitation medical record summary sheet covered four major sections: inpatient information, hospitalization information, diagnosis and treatment information, and cost information. ICD-10/ICD-11 were the standards and coding tools for admission and discharge diagnoses in the inpatient rehabilitation medical record summary sheet. The three functional assessment tools recommended by ICD-11, the 36-item version of World Health Organization Disability Assessment Schedule 2.0, Brief Model Disability Survey and Generic Functioning domains, as well as ICF, were used for rehabilitation functioning assessment and the coding of outcomes. ICHI Beta-3 and ICD-9-CM-3 were used for coding surgical procedures and operations in the medical record summary sheet, and also for coding rehabilitation intervention items. ConclusionThe inpatient rehabilitation medical record summary sheet is a summary of the relevant content of the rehabilitation medical record and a tool for reporting inpatient rehabilitation data. It needs to be refined and optimized according to the characteristics of rehabilitation, with necessary data supplemented. The application of ICD-11/ICD-10, ICF and ICHI Beta-3/ICD-9-CM-3 classification standards would comprehensively promote the accuracy of inpatient diagnosis of diseases and functions. Based on ICD-11 and ICF, relevant functional assessment result data would be added, and ICHI Beta-3/ICD-9-CM-3 should be used to code rehabilitation interventions. Improving the quality of rehabilitation medical records and inpatient rehabilitation medical record summary sheet is an important part of rehabilitation quality control, and also lays an evidence-based data foundation for the analysis and application of inpatient rehabilitation medical record summary sheet.
8.Effects of ovarian torsional reduction in young rats on ovary tissue structure and reproductive function on torsional side in adult stage
Zhongyan ZHANG ; Hong MA ; Kaixin LI ; Peng ZHAO ; Guangxu ZHOU ; Bin LIU ; Guangyou LANG
Chongqing Medicine 2025;54(1):31-36
Objective To conduct the reductive reservation for torsional ovary in different states(.un-necrotic ovary,suspected necrotic torsional ovary and torsional necrotic ovary)after the ovarian torsion in pre-maturity SD rat,and to investigate its effect on the ovarian reproductive function in maturity stage.Methods A total of 32 SD rats with 3 weeks old were selected and randomly divided into 4 groups,8 cases in each group.The animal model of ovarian torsion was made by using the Turner method,which was similar to the animal model of testicular torsion,and either group was selected to undergo the sham operation as the con-trol group(CG group).The non-necrotic torsional ovary detorsion group(NNTOD group),suspected necrotic torsional ovary detorsion group(SNTOD group)and necrotic torsional ovary detorsion group(NTOD group)were established respectively.When the animals were fed to sexual maturity at 8 weeks of age,the experimen-tal animals were sacrificed by vertebral dislocation method,and the ovary tissues on the torsional side were cut for HE staining and transmission electron microscopy to examine the changes of ovarian histomorphology and mitochondrial structure.Ovarian cell apoptosis was detected by Tunel assay.ELISA method was used to de-tect the follicle-stimulating hormone(FSH),luteinizing hormone(LH)and anti-mullerian duct hormone(AMH)levels in centrifugal blood.Results The ovarian structure in the CG group and NNTOD group was clear,the ovarian follicles at different levels were developed well;the electron microscopy showed normal mi-tochondria.The ovarian partial structure in the SNTOD group was disorganized,the number of follicles at all levels of growth was decreased;electron microscopic examination showed a little damage of mitochondria.In the NTOD group,the arrangement of ovarian structure was obviously disordered,the number of growing folli-cles at all levels was significantly reduced;the electron microscopy showed that most of the mitochondria were obviously swollen and severely damaged.Compared with the CG group,the apoptosis rate in the SNTOD group and NTOD group was significantly increased(P<0.05).There was no statistically significant differ-ence between CG group and NNTOD group(P>0.05).Compared with the NTOD group,the apoptosis rate in the SNTOD group was decreased(P<0.05).Compared with the CG group,the levels of LH and FSH in the SNTOD and NTOD groups were increased,and the AMH level was decreased(P<0.05).The LH and FSH levels in the SNTOD group were lower than those in the NTOD group,the AMH level was higher than that in the NTOD group(P<0.05).Conclusion After reduction of the torsional suspected necrotic ovary in the prematurity rat,the ovarian reproductive function in the torsional side during sexual maturity period is slightly injured;while after reduction of torsional necrotic ovary restoration,its reproductive function is appar-ently damaged.
9.Effect of high-frequency repetitive transcranial magnetic stimulation on upper limb function of stroke patients based on motor sequence learning
Wanting SUN ; Ailipinai YASEN ; Xiang GONG ; Yue XIAO ; Zhaodan GAN ; Mingjie LIU ; Lanting ZENG ; Shuyue MA ; Jun LU ; Guangxu XU
Chinese Journal of Rehabilitation Theory and Practice 2025;31(7):812-821
Objective To investigate the effects of high-frequency repetitive transcranial magnetic stimulation(HF-rTMS)applied to the supplementary motor area(SMA)or primary motor cortex(M1)on upper limb function in stroke patients in terms of motor sequence learning.Methods From April,2024 to February,2025,60 inpatients were recruited from the First Affiliated Hospital with Nan-jing Medical University.They were randomly assigned into the control group,SMA group and M1 group,with 20 patients in each group.All the groups received medication and conventional rehabilitation.On this basis,SMA group underwent HF-rTMS on the affected side's SMA,while M1 group received HF-rTMS on the affected side's M1 for two weeks.All the groups were measured with motor evoked potentials(MEP),the serial reaction time(RT)task,Fugl-Meyer Assessment-Upper Extremities(FMA-UE)and modified Barthel Index(MBI)before and after intervention.Results The SMA and M1 groups dropped one case respectively.MEP elicitation rate of the affected side's increased in SMA and M1 groups(P<0.05),and it was better than that in the control group(χ2>4.792,P<0.05).The intra-group effects of RTsequential sequence,FMA-UE and MBI scores were significant(|F|>81.546,P<0.05).The inter-group effects of RTrandom sequence,RTsequential sequence,?RT,and MBI scores were significant(F>3.228,P<0.05).The in-teractive effects of RTrandom sequence,RTsequential sequence,?RT,FMA-UE and MBI scores were significant(|F|>3.520,P>0.05).After intervention,RTsequential sequence,?RT,FMA-UE and MBI scores improved(P<0.05).RTrandom sequence was lower in SMA group than in the control group(P<0.017),RTsequential sequence,?RT,FMA-UE and MBI scores im-proved more in SMA and M1 groups than in the control group(P<0.05),but no significant difference was found between the SMA group and the M1 group(P>0.05).Conclusion HF-rTMS applied to the affected SMA or M1 can activate motor sequence learning and promote the recov-ery of upper limb function in stroke patients.
10.Epidemiological characteristics of febrile seizure among children under 6 years old in Ningbo City from 2015 to 2021
Guangxu LIU ; Liang ZHANG ; Houyu ZHAO ; Siwei DENG ; Junting YANG ; Ning LI ; Rui MA ; Yan HE ; Guozhang XU ; Zhike LIU ; Siyan ZHAN
Journal of Peking University(Health Sciences) 2025;57(3):584-591
Objective:To describe the epidemiological characteristics and changes of febrile seizure(FS)among children under 6 years old in Ningbo City,Zhejiang Province from 2015 to 2021.Methods:Based on the Ningbo Regional Health Information Platform,a dynamic cohort was established using vacci-nation registration information,and the cases of FS were identified by the diagnostic results of Chinese terms or International Classification of Diseases 10th revision(ICD-10)R56.0 code in the electronic medical records.The first visit of FS during the observation period was defined as a new case,and a re-currence case was defined as the case with a visit interval of more than 7 days.The 95%confidence in-terval(CI)of FS incidence density was calculated by the Poisson distribution.Results:From January 2015 to June 2020,there were 1.3 million children under 6 years old in Ningbo,with male accounting for 52.87%.The median follow-up time was 2.83(1.55-4.00)years.During the follow-up period,12 776 new onset cases had FS,with more males than females,with an overall incidence density of 4.34(95%CI:4.27-4.40)/1 000 person-years and a recurrence rate of 21.63%.There was a higher inci-dence density in children who were male,born in Ningbo and of non-mobility.The incidence density of FS was higher in urban areas than in rural and rural-urban fringe areas,and the incidence density was different among districts and counties.The peak density was found in children aged 18-23 months[8.42(95%CI:8.11-8.74)/1 000 person-years].From 2015 to 2019,the incidence density in-creased with calendar year(Ptrend<0.001),and the highest was 5.62(95%CI:5.43-5.81)/1 000 person-years.The incidence density of FS decreased significantly during the period between 2020 and 2021.The incidence density was higher in winter.Conclusion:From 2015 to 2019,the overall inci-dence density of FS in children under 6 years old in Ningbo City presented an increasing trend.More at-tention should be paid to the health education,the improvement of the health maintenance model,the en-hancement of the cognition of FS,the identification and treatment of FS among high-risk population and regions so as to prevent its recurrence and reduce the disease burden during the corona virus disease 2019(COVID-19)epide-mic.

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