1.Inhibitory effect of pterostilbene on high glucose-mediated endothelial-to-mesenchymal transition in human retinal microvascular endothelial cells
Xiaolan* WANG ; Hanyi* YANG ; Yimeng ZHANG ; Sida LIU ; Chengming CHEN ; Tingke XIE ; Yixuan CHEN ; Jiayi NING ; Jing HAN
International Eye Science 2025;25(3):359-364
AIM: To investigate the potential inhibitory effect of pterostilbene on the endothelial-to-mesenchymal transition(EndMT)induced by high glucose conditions in human retinal microvascular endothelial cells(HRMECs).METHODS: The optimal concentration of pterostilbene for treating HRMECs was determined using the CCK-8 assay, with 12.5 and 25 μmol/L concentrations selected for subsequent experiments. Four experimental groups were established: control group, high glucose group, high glucose combined with 12.5 μmol/L pterostilbene treatment group, and high glucose combined with 25 μmol/L pterostilbene treatment group. The expression levels of HDAC7 and EndMT-associated markers were detected via Western blot analysis. Cell migration ability was assessed using Transwell migration assays and scratch wound healing tests, while vasculogenic capability was evaluated through tube formation assays.RESULTS: The CCK-8 assay revealed that pterostilbene at a concentration of 22.07 μmol/L inhibited 50% of cell viability in HRMECs. Western blot analysis demonstrated that compared with the control group, the expression levels of HDAC7, ZEB1, Vimentin, and Snail were significantly upregulated in HRMECs cultured in high glucose(all P<0.01), while the expressions of VE-cadherin and CD31 were significantly reduced(all P<0.01). Compared to the high glucose group, the treatment with 12.5 and 25 μmol/L pterostilbene significantly reduced the expression of HDAC7, ZEB1, Vimentin, and Snail under high glucose conditions(all P<0.01). Notably, 25 μmol/L pterostilbene enhanced the expression of VE-cadherin and CD31(all P<0.01). Scratch wound healing tests revealed that HRMECs treated with high glucose exhibited a significantly increased cell migration rate compared to the control group(P<0.05), while the application of 25 μmol/L pterostilbene significantly suppressed HRMECs migration under high glucose conditions(P<0.01). Transwell migration assays demonstrated that the cell migration rate in the high glucose group was significantly higher than that in the control group(P<0.01), with cell migration rate markedly reduced following treatment with both of 12.5 and 25 μmol/L pterostilbene(all P<0.01). The tube formation assay revealed that the ability of HRMECs to form tubular structures was significantly enhanced under high glucose conditions(P<0.01), and both 12.5 and 25 μmol/L of pterostilbene effectively inhibited this effect(all P<0.01).CONCLUSION: Pterostilbene can inhibit HDAC7 expression, suppress EndMT-mediated migration of HRMECs, and impair tube formation under high-glucose conditions.
2.Inhibitory effect of pterostilbene on high glucose-mediated endothelial-to-mesenchymal transition in human retinal microvascular endothelial cells
Xiaolan* WANG ; Hanyi* YANG ; Yimeng ZHANG ; Sida LIU ; Chengming CHEN ; Tingke XIE ; Yixuan CHEN ; Jiayi NING ; Jing HAN
International Eye Science 2025;25(3):359-364
AIM: To investigate the potential inhibitory effect of pterostilbene on the endothelial-to-mesenchymal transition(EndMT)induced by high glucose conditions in human retinal microvascular endothelial cells(HRMECs).METHODS: The optimal concentration of pterostilbene for treating HRMECs was determined using the CCK-8 assay, with 12.5 and 25 μmol/L concentrations selected for subsequent experiments. Four experimental groups were established: control group, high glucose group, high glucose combined with 12.5 μmol/L pterostilbene treatment group, and high glucose combined with 25 μmol/L pterostilbene treatment group. The expression levels of HDAC7 and EndMT-associated markers were detected via Western blot analysis. Cell migration ability was assessed using Transwell migration assays and scratch wound healing tests, while vasculogenic capability was evaluated through tube formation assays.RESULTS: The CCK-8 assay revealed that pterostilbene at a concentration of 22.07 μmol/L inhibited 50% of cell viability in HRMECs. Western blot analysis demonstrated that compared with the control group, the expression levels of HDAC7, ZEB1, Vimentin, and Snail were significantly upregulated in HRMECs cultured in high glucose(all P<0.01), while the expressions of VE-cadherin and CD31 were significantly reduced(all P<0.01). Compared to the high glucose group, the treatment with 12.5 and 25 μmol/L pterostilbene significantly reduced the expression of HDAC7, ZEB1, Vimentin, and Snail under high glucose conditions(all P<0.01). Notably, 25 μmol/L pterostilbene enhanced the expression of VE-cadherin and CD31(all P<0.01). Scratch wound healing tests revealed that HRMECs treated with high glucose exhibited a significantly increased cell migration rate compared to the control group(P<0.05), while the application of 25 μmol/L pterostilbene significantly suppressed HRMECs migration under high glucose conditions(P<0.01). Transwell migration assays demonstrated that the cell migration rate in the high glucose group was significantly higher than that in the control group(P<0.01), with cell migration rate markedly reduced following treatment with both of 12.5 and 25 μmol/L pterostilbene(all P<0.01). The tube formation assay revealed that the ability of HRMECs to form tubular structures was significantly enhanced under high glucose conditions(P<0.01), and both 12.5 and 25 μmol/L of pterostilbene effectively inhibited this effect(all P<0.01).CONCLUSION: Pterostilbene can inhibit HDAC7 expression, suppress EndMT-mediated migration of HRMECs, and impair tube formation under high-glucose conditions.
3.Effect Analysis of Different Interventions to Improve Neuroinflammation in The Treatment of Alzheimer’s Disease
Jiang-Hui SHAN ; Chao-Yang CHU ; Shi-Yu CHEN ; Zhi-Cheng LIN ; Yu-Yu ZHOU ; Tian-Yuan FANG ; Chu-Xia ZHANG ; Biao XIAO ; Kai XIE ; Qing-Juan WANG ; Zhi-Tao LIU ; Li-Ping LI
Progress in Biochemistry and Biophysics 2025;52(2):310-333
Alzheimer’s disease (AD) is a central neurodegenerative disease characterized by progressive cognitive decline and memory impairment in clinical. Currently, there are no effective treatments for AD. In recent years, a variety of therapeutic approaches from different perspectives have been explored to treat AD. Although the drug therapies targeted at the clearance of amyloid β-protein (Aβ) had made a breakthrough in clinical trials, there were associated with adverse events. Neuroinflammation plays a crucial role in the onset and progression of AD. Continuous neuroinflammatory was considered to be the third major pathological feature of AD, which could promote the formation of extracellular amyloid plaques and intracellular neurofibrillary tangles. At the same time, these toxic substances could accelerate the development of neuroinflammation, form a vicious cycle, and exacerbate disease progression. Reducing neuroinflammation could break the feedback loop pattern between neuroinflammation, Aβ plaque deposition and Tau tangles, which might be an effective therapeutic strategy for treating AD. Traditional Chinese herbs such as Polygonum multiflorum and Curcuma were utilized in the treatment of AD due to their ability to mitigate neuroinflammation. Non-steroidal anti-inflammatory drugs such as ibuprofen and indomethacin had been shown to reduce the level of inflammasomes in the body, and taking these drugs was associated with a low incidence of AD. Biosynthetic nanomaterials loaded with oxytocin were demonstrated to have the capability to anti-inflammatory and penetrate the blood-brain barrier effectively, and they played an anti-inflammatory role via sustained-releasing oxytocin in the brain. Transplantation of mesenchymal stem cells could reduce neuroinflammation and inhibit the activation of microglia. The secretion of mesenchymal stem cells could not only improve neuroinflammation, but also exert a multi-target comprehensive therapeutic effect, making it potentially more suitable for the treatment of AD. Enhancing the level of TREM2 in microglial cells using gene editing technologies, or application of TREM2 antibodies such as Ab-T1, hT2AB could improve microglial cell function and reduce the level of neuroinflammation, which might be a potential treatment for AD. Probiotic therapy, fecal flora transplantation, antibiotic therapy, and dietary intervention could reshape the composition of the gut microbiota and alleviate neuroinflammation through the gut-brain axis. However, the drugs of sodium oligomannose remain controversial. Both exercise intervention and electromagnetic intervention had the potential to attenuate neuroinflammation, thereby delaying AD process. This article focuses on the role of drug therapy, gene therapy, stem cell therapy, gut microbiota therapy, exercise intervention, and brain stimulation in improving neuroinflammation in recent years, aiming to provide a novel insight for the treatment of AD by intervening neuroinflammation in the future.
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.Traditional Chinese Medicine Intervention in Diarrhea-predominant Irritable Bowel Syndrome Based on Gut-brain Axis: A Review
Jinchan PENG ; Jinxiu WEI ; Zhu LIU ; Lijian LIU ; Liqun LI ; Chengning YANG ; Guangwen CHEN ; Jianfeng LI ; Sheng XIE
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(8):311-319
Diarrhea-predominant irritable bowel syndrome (IBS-D) is a common digestive system disease with high prevalence and recurrence rates for years, high treatment costs, and serious impacts on patients' quality of life and economic burden. Therefore, it is important to explore new and safe treatment methods. The pathogenesis of IBS-D is complex, in which the gut-brain axis is a key factor. The gut-brain axis, a bidirectional signaling pathway connecting the gastrointestinal tract and the central nervous system, regulates gastrointestinal motility, secretion, and immune responses, playing a key role in the occurrence and development of IBS-D. Up to now, antidiarrheal agents, probiotics, and neurotransmitter modulators are the main methods for the clinical treatment of IBS-D. Although they can partially curb the progression of this disease, the therapeutic effects remain to be improved. Studies have confirmed that traditional Chinese medicine (TCM) has significant advantages in the treatment of IBS-D since it can regulate the gut-brain axis via multiple pathways and targets to improve the gastrointestinal motility and strengthen immune defenses. However, there is a lack of systematic reviews on the regulation of the gut-brain axis by TCM in the treatment of IBS-D. Based on the review of IBS-D-related articles published in recent years, this paper systematically summarized the relationship between the gut-brain axis and IBS-D and the role of TCM in the treatment, providing new ideas for the treatment of IBS-D.
9.Sequential Administration of Dihuang Baoyuan Granules and Fuling Yunhua Granules for Teating Type 2 Diabetes Mellitus in Mice
Huiyi XIE ; Junran CHEN ; Boning HUANG ; Xinrong YANG ; Fangle LIU ; Yuying ZHENG ; Haiyu ZHAO ; Tianbao HU ; Baoqin LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):155-163
ObjectiveTo investigate the therapeutic effect of sequential administration of Dihuang Baoyuan granules (DHBY, the prescription for consolidating body resistance) and Fuling Yunhua granules (FLYH, the prescription for treating symptoms) on spontaneous type 2 diabetes mellitus (T2DM) in mice. MethodsAccording to the fasting blood glucose (FBG) level, 12-week-old db/db mice were randomized into six groups: model, DHBY (18.02 g·kg-1), FLYH (14.80 g·kg-1), sequential administration 1 (SEQ-1, DHBY 18.02 g·kg-1+FLYH 14.80 g·kg-1), sequential administration 2 (SEQ-2, FLYH 14.80 g·kg-1+DHBY 18.02 g·kg-1), and dapagliflozin (Dapa, 1.3 mg·kg-1). The m/m mice in the same litter were selected as the normal group. The mice were administrated with corresponding drugs by gavage for 8 consecutive weeks. During the 8 weeks of drug administration and 2 weeks after withdrawal, the retinal thickness, FBG, hemoglobin A1c (HbA1c), and insulin were determined, and histopathological changes of the pancreas, liver, kidney, and retina were observed by hematoxylin-eosin (HE) staining. ResultsCompared with the model group, SEQ-1 for 4 weeks lowered the FBG level (P<0.05), raised the insulin level, decreased the triglyceride (TG) level (P<0.05), increased the number of optic ganglion cells and diminished vacuolar degeneration of pancreatic islet and liver. SEQ-2 lowered FBG and HbA1c levels (P<0.05), rose the insulin level, increased the retinal thickness and the number of optic ganglion cells (P<0.05), and alleviated vacuolar degeneration of pancreatic islet and liver. Two weeks after drug withdrawal, Dapa tended to increase FBG and HbA1c compared with those at the time of drug withdrawal. However, the levels of FBG and HbA1c in the SEQ-2 group remained decreasing (P<0.05). ConclusionSEQ-1 and SEQ-2 can lower the blood glucose level and ameliorate diabetic retinopathy, and SEQ-2 outperformed DHBY and FLYH in lowering the blood glucose level. Moreover, SEQ-2 can maintain the blood glucose-lowering effect after drug withdrawal.
10.Sequential Administration of Dihuang Baoyuan Granules and Fuling Yunhua Granules for Teating Type 2 Diabetes Mellitus in Mice
Huiyi XIE ; Junran CHEN ; Boning HUANG ; Xinrong YANG ; Fangle LIU ; Yuying ZHENG ; Haiyu ZHAO ; Tianbao HU ; Baoqin LIN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(11):155-163
ObjectiveTo investigate the therapeutic effect of sequential administration of Dihuang Baoyuan granules (DHBY, the prescription for consolidating body resistance) and Fuling Yunhua granules (FLYH, the prescription for treating symptoms) on spontaneous type 2 diabetes mellitus (T2DM) in mice. MethodsAccording to the fasting blood glucose (FBG) level, 12-week-old db/db mice were randomized into six groups: model, DHBY (18.02 g·kg-1), FLYH (14.80 g·kg-1), sequential administration 1 (SEQ-1, DHBY 18.02 g·kg-1+FLYH 14.80 g·kg-1), sequential administration 2 (SEQ-2, FLYH 14.80 g·kg-1+DHBY 18.02 g·kg-1), and dapagliflozin (Dapa, 1.3 mg·kg-1). The m/m mice in the same litter were selected as the normal group. The mice were administrated with corresponding drugs by gavage for 8 consecutive weeks. During the 8 weeks of drug administration and 2 weeks after withdrawal, the retinal thickness, FBG, hemoglobin A1c (HbA1c), and insulin were determined, and histopathological changes of the pancreas, liver, kidney, and retina were observed by hematoxylin-eosin (HE) staining. ResultsCompared with the model group, SEQ-1 for 4 weeks lowered the FBG level (P<0.05), raised the insulin level, decreased the triglyceride (TG) level (P<0.05), increased the number of optic ganglion cells and diminished vacuolar degeneration of pancreatic islet and liver. SEQ-2 lowered FBG and HbA1c levels (P<0.05), rose the insulin level, increased the retinal thickness and the number of optic ganglion cells (P<0.05), and alleviated vacuolar degeneration of pancreatic islet and liver. Two weeks after drug withdrawal, Dapa tended to increase FBG and HbA1c compared with those at the time of drug withdrawal. However, the levels of FBG and HbA1c in the SEQ-2 group remained decreasing (P<0.05). ConclusionSEQ-1 and SEQ-2 can lower the blood glucose level and ameliorate diabetic retinopathy, and SEQ-2 outperformed DHBY and FLYH in lowering the blood glucose level. Moreover, SEQ-2 can maintain the blood glucose-lowering effect after drug withdrawal.

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