1.Research on Building a Performance Evaluation Index System for the Specialty Cooperation Alliance in Hospital-Community
Yuying WANG ; Fei ZHANG ; Dongbao ZHAO ; Yi FAN ; Quancheng XU ; Lijin CHEN ; Yixiang HUANG
Chinese Hospital Management 2025;45(5):59-62
Objective To construct the performance evaluation index system of specialist cooperation alliance in hos-pital-community in order to scientifically evaluate the effect of the construction of the specialist cooperation alliance.Methods By searching literature related to the construction of specialized league,sort out national and local policy documents,and the"structure-process-result"model was adopted to initially construct the index system.The ex-pert letter consultation form of the indicator system was formed through the discussion of the special group,two rounds of Delphi expert consultation were carried out to determine the evaluation indicator system,and the weight coefficient of each indicator was determined by the simultaneous application of analytic hierarchy process.Results The effective recovery rates of the two rounds of questionnaire were 84.62%and 100.00%,respectively.The positive de-gree of experts was high,and the average authority degree of experts was 0.864.The importance,operability,sen-sitivity Kendall's W coefficient and x2 test value of all indexes were P<0.05.Finally,an evaluation index system covering 9 first-level indicators and 25 second-level indicators was established.Conclusion The constructed perfor-mance evaluation index is scientific and reliable.The practical application shows that it can be used as a tool to evalu-ate the effect of integrated,continuous and collaborative health service delivery in hospital-community.
2.Application of SPARK learning model combined with five-step questioning method in standardized training of residents in the department of thyroid and breast surgery
Yixiang HUANG ; Gang WANG ; Yanni HUANG ; Lei CHEN
Chinese Journal of Medical Education Research 2025;24(10):1350-1356
Objective:To combine the SPARK learning model with five-step questioning method, construct a new teaching regimen, and evaluate its effectiveness in the resident training in the department of thyroid and breast surgery, and to provide theoretical basis and practical reference for optimizing the training model of specialist physicians.Methods:A total of 104 clinicians in the department of thyroid and breast surgery who participated in standardized training from December 2022 to December 2024 were selected as research subjects. Based on the time of teaching reform (January 2024), 52 clinicians who participated in standardized training from December 2022 to December 2023 were included in the control group; they received the routine teaching method mainly based on the linear teaching process of "theory teaching, clinical demonstration, skill training, and case discussion", which emphasized knowledge transmission and skill imitation. The 52 clinicians who participated in standardized training from January to December 2024 were assigned to the experimental group; they received SPARK learning model combined with the five-step question teaching method. Teaching evaluation included assessment of basic theory, clinical skills, and clinical thinking as well as satisfaction with teaching. The t test and chi-square test were performed using SPSS 26.0. Results:The basic theory assessment and clinical skill assessment scores were significantly higher in the experimental group than in the control group. The scores of all thinking ability dimensions were significantly higher in the experimental group than in the control group [diagnostic decision-making: (21.85±1.15) vs. (18.35±3.42); treatment plan: (24.62±1.52) vs. (20.28±4.13); complication management: (14.82±0.73) vs. (12.17±2.53); evidence-based medicine application: (15.18±0.92) vs. (12.48±2.85); multidisciplinary collaboration: (14.95±0.83) vs. (12.73±3.08); and cost benefit analysis: (8.25±0.42) vs. (6.82±1.53)]. The satisfaction scores were significantly higher in the experimental group than in the control group.Conclusions:Through the organic combination of systematic knowledge construction and critical thinking training, the teaching method integrating SPARK learning model and five-step questioning method can significantly enhance the specialized core competence of residents in the department of thyroid and breast surgery and their decision-making ability to cope with complex clinical scenarios.
3.Astragali Radix Polysaccharide Inhibits Proliferation and Migration of Gastric Cancer Cells by Targeting ID1 and Akt
Peizheng SHI ; Shanshan XIAO ; Xinjiang ZHANG ; Yixiang NIE ; Xianchao WANG ; Jing HUANG ; Jie MEI ; Huaquan LAN ; Tuanyun JI ; Tianyi ZHANG ; Xiaoyong WEI ; Qiaohong YANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(15):96-105
ObjectiveTo explore the regulatory effects and mechanisms of Astragali Radix polysaccharide (APS) on inhibitor of differentiation1 (ID1) and protein kinase B (Akt) in gastric cancer. MethodsImmunohistochemical staining was used to detect the expression of ID1 and Akt in 61 gastric cancer tissue samples and 20 adjacent normal gastric tissue samples. Immunofluorescence was used to detect the localization of ID1 and Akt. The effects of APS at the concentrations of 0.625, 1.25, 2.5, 5, 10, 20 mg·L-1 on the proliferation of gastric cancer MGC-803 cells were examined by the cell counting kit-8(CCK-8) method and the colony formation assay. The target information of APS was retrieved from the Traditional Chinese Medicine Systems Pharmacology and Analysis Platform and Swiss Target Prediction. Keywords such as gastric cancer, gastric tumor, and stomach cancer were searched against GeneCards, UniProt, DisGeNET, and Online Mendelian Inheritance in Man (OMIM) for the screening of gastric cancer-related targets. The online tool jvenn was used to create the Venn diagram to identify the common targets, and STRING and Cytoscape were used to construct the protein-protein interaction network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted via R 4.2.2 to predict the potential roles of APS in the development of gastric cancer. The cell scratch assay was employed to assess the effect of APS on the migration of MGC-803 cells. The protein and mRNA levels of ID1 and Akt in the cells treated with APS were determined by Western blot and Real-time PCR, respectively. ResultsCompared with the adjacent normal gastric tissue, the gastric adenocarcinoma tissue showed increased positive expression of ID1 (χ2 =81.00, P<0.01). Immunofluorescence detection showed that ID1 and Akt were mainly located in the cytoplasm of gastric adenocarcinoma cells. Bioinformatics analysis identified 14 common genes shared between APS and gastric cancer. The average degree of protein-protein interaction network nodes was 14.29. GO and KEGG pathway enrichment results showed that ID1 and Akt were significantly enriched in the Rap1 and phosphatidylinositol-3-kinase (PI3K) /Akt signaling pathways. Cell experiments demonstrated that 5-fluorouracil (0.1 mg·L-1) and APS (10, 20 mg·L-1) groups showed decreased cell proliferation, migration, and colony formation. Compared with the control group, 10, 20 mg·L-1 APS inhibited the proliferation of MGC-803 cells (P<0.01), with 10 mg·L-1 APS demonstrating stronger inhibitory effect. In addition, APS at 10, 20 mg·L-1 inhibited the migration (P<0.01) and colony formation (P<0.05, P<0.01) of MGC-803 cells. Compared with the control group, APS at 10, 20 mg·L-1 down-regulated the protein levels of ID1 (P<0.01) and Akt (P<0.05) and the mRNA levels of ID1 (P<0.05, P<0.01) and Akt (P<0.05, P<0.01) in MGC-803 cells. ConclusionID1 and Akt are highly expressed in the gastric adenocarcinoma tissue, which may be related to the development of gastric cancer. APS can down-regulate the protein and mRNA levels of ID1 and Akt to exert anti-tumor effects, which is expected to provide new therapeutic targets for gastric cancer treatment.
4.Analysis of 41 cases of myocardial infarction in children with coronary artery lesion after Kawasaki disease
Aiting LYU ; Lan YE ; Chen CHU ; Lan HE ; Quming ZHAO ; Lu ZHAO ; Feng WANG ; Yixiang LIN ; Shuna SUN ; Guoying HUANG ; Fang LIU
Chinese Journal of Pediatrics 2025;63(2):157-162
Objective:To analyze the clinical characteristics,diagnosis and treatment of pediatric myocardial infarction (MI) patients with coronary artery lesions (CAL) after Kawasaki disease (KD).Methods:Clinical data including baseline characteristics, KD and CAL information, clinical symptoms at MI onset, electrocardiogram (ECG) and imaging findings, MI treatment, and clinical outcomes of 41 MI patients with CAL after KD admitted to the Children′s Hospital of Fudan University from January 2017 to August 2024 were analyzed retrospectively.Results:(1) Demographic characteristics: a total of 41 patients were included (36 males and 5 females). The age at MI was 4.6 (2.3, 5.7) years, and time from KD onset to MI was 397 (50, 1 095) d. (2) Treatment of acute KD: only 15 patients (37%) received standard initial treatment within 10 days of KD onset with intravenous immunoglobulin 2 g/kg. The other 26 cases (63%) received non-standard treatment or no treatment. (3) Treatment of CAL before MI: the time from KD onset to CAL was 14 (10, 116) d, with CAL not identified before MI onset in 15 patients. Among the 26 cases diagnosed with CAL prior to MI, 9 cases received only single or dual antiplatelet drug, of which 7 cases received oral dipyridamole. The remaining 16 cases received antiplatelet drug combined with warfarin, but only 1 case achieved the target international standardized ratio of 1.5-2.5. Out of all 41 cases, only 1 case (2%) received standard antithrombotic treatment before MI onset. (4) Clinical symptoms of MI: at MI onset, 32 patients presented with different clinical symptoms, with typical MI symptoms such as chest tightness, chest pain, precordial discomfort in 18 cases, and cardiopulmonary arrest accompanied by syncope or convulsions in 10 cases. Other non-specific symptoms included abdominal pain, nausea, vomiting and pallor. Nine patients were asymptomatic and were found to have silent MI on follow-up. (5) ECG and imaging findings: ECG showed ST-T changes in 33 cases, and abnormal Q waves, and arrhythmias in the remaining patients; echocardiography indicated coronary artery aneurysm with thrombosis in 27 cases, reduced left ventricular ejection fraction in 18 cases, abnormal wall motion in 15 cases, and ventricular aneurysm in 3 cases. Thirty-seven patients underwent coronary angiography and (or) multi-slice spiral CT angiography, with 39 occluded vessels and 3 severe stenosis (≥75%), all of which were caused by giant aneurism with thrombus formation. (6) Treatment of MI: of the 32 patients with acute MI, 9 patients received successful cardiopulmonary resuscitation, 7 patients received intravenous thrombolysis, and 1 patient underwent percutaneous coronary balloon angioplasty. All of these patients received dual antiplatelet drugs and low-molecular-weight heparin at therapeutic doses following MI treatment. Sixteen patients received coronary artery bypass graft (CABG) treatment, all of which were successful. (7) Outcomes: the follow-up time was 994 (215, 1 832) d. Thirty-one patients showed improvement, 5 patients experienced disease progression or no change, 1 patient died, and 4 patients were lost to follow-up.Conclusions:MI in children with CAL after KD often occurs within 1 year after the onset of KD. MI can present with atypical clinical symptoms in children. CABG is the main treatment option in children severe CAL after KD who developed MI.
5.Application of SPARK learning model combined with five-step questioning method in standardized training of residents in the department of thyroid and breast surgery
Yixiang HUANG ; Gang WANG ; Yanni HUANG ; Lei CHEN
Chinese Journal of Medical Education Research 2025;24(10):1350-1356
Objective:To combine the SPARK learning model with five-step questioning method, construct a new teaching regimen, and evaluate its effectiveness in the resident training in the department of thyroid and breast surgery, and to provide theoretical basis and practical reference for optimizing the training model of specialist physicians.Methods:A total of 104 clinicians in the department of thyroid and breast surgery who participated in standardized training from December 2022 to December 2024 were selected as research subjects. Based on the time of teaching reform (January 2024), 52 clinicians who participated in standardized training from December 2022 to December 2023 were included in the control group; they received the routine teaching method mainly based on the linear teaching process of "theory teaching, clinical demonstration, skill training, and case discussion", which emphasized knowledge transmission and skill imitation. The 52 clinicians who participated in standardized training from January to December 2024 were assigned to the experimental group; they received SPARK learning model combined with the five-step question teaching method. Teaching evaluation included assessment of basic theory, clinical skills, and clinical thinking as well as satisfaction with teaching. The t test and chi-square test were performed using SPSS 26.0. Results:The basic theory assessment and clinical skill assessment scores were significantly higher in the experimental group than in the control group. The scores of all thinking ability dimensions were significantly higher in the experimental group than in the control group [diagnostic decision-making: (21.85±1.15) vs. (18.35±3.42); treatment plan: (24.62±1.52) vs. (20.28±4.13); complication management: (14.82±0.73) vs. (12.17±2.53); evidence-based medicine application: (15.18±0.92) vs. (12.48±2.85); multidisciplinary collaboration: (14.95±0.83) vs. (12.73±3.08); and cost benefit analysis: (8.25±0.42) vs. (6.82±1.53)]. The satisfaction scores were significantly higher in the experimental group than in the control group.Conclusions:Through the organic combination of systematic knowledge construction and critical thinking training, the teaching method integrating SPARK learning model and five-step questioning method can significantly enhance the specialized core competence of residents in the department of thyroid and breast surgery and their decision-making ability to cope with complex clinical scenarios.
6.Research on Building a Performance Evaluation Index System for the Specialty Cooperation Alliance in Hospital-Community
Yuying WANG ; Fei ZHANG ; Dongbao ZHAO ; Yi FAN ; Quancheng XU ; Lijin CHEN ; Yixiang HUANG
Chinese Hospital Management 2025;45(5):59-62
Objective To construct the performance evaluation index system of specialist cooperation alliance in hos-pital-community in order to scientifically evaluate the effect of the construction of the specialist cooperation alliance.Methods By searching literature related to the construction of specialized league,sort out national and local policy documents,and the"structure-process-result"model was adopted to initially construct the index system.The ex-pert letter consultation form of the indicator system was formed through the discussion of the special group,two rounds of Delphi expert consultation were carried out to determine the evaluation indicator system,and the weight coefficient of each indicator was determined by the simultaneous application of analytic hierarchy process.Results The effective recovery rates of the two rounds of questionnaire were 84.62%and 100.00%,respectively.The positive de-gree of experts was high,and the average authority degree of experts was 0.864.The importance,operability,sen-sitivity Kendall's W coefficient and x2 test value of all indexes were P<0.05.Finally,an evaluation index system covering 9 first-level indicators and 25 second-level indicators was established.Conclusion The constructed perfor-mance evaluation index is scientific and reliable.The practical application shows that it can be used as a tool to evalu-ate the effect of integrated,continuous and collaborative health service delivery in hospital-community.
7.Analysis of 41 cases of myocardial infarction in children with coronary artery lesion after Kawasaki disease
Aiting LYU ; Lan YE ; Chen CHU ; Lan HE ; Quming ZHAO ; Lu ZHAO ; Feng WANG ; Yixiang LIN ; Shuna SUN ; Guoying HUANG ; Fang LIU
Chinese Journal of Pediatrics 2025;63(2):157-162
Objective:To analyze the clinical characteristics,diagnosis and treatment of pediatric myocardial infarction (MI) patients with coronary artery lesions (CAL) after Kawasaki disease (KD).Methods:Clinical data including baseline characteristics, KD and CAL information, clinical symptoms at MI onset, electrocardiogram (ECG) and imaging findings, MI treatment, and clinical outcomes of 41 MI patients with CAL after KD admitted to the Children′s Hospital of Fudan University from January 2017 to August 2024 were analyzed retrospectively.Results:(1) Demographic characteristics: a total of 41 patients were included (36 males and 5 females). The age at MI was 4.6 (2.3, 5.7) years, and time from KD onset to MI was 397 (50, 1 095) d. (2) Treatment of acute KD: only 15 patients (37%) received standard initial treatment within 10 days of KD onset with intravenous immunoglobulin 2 g/kg. The other 26 cases (63%) received non-standard treatment or no treatment. (3) Treatment of CAL before MI: the time from KD onset to CAL was 14 (10, 116) d, with CAL not identified before MI onset in 15 patients. Among the 26 cases diagnosed with CAL prior to MI, 9 cases received only single or dual antiplatelet drug, of which 7 cases received oral dipyridamole. The remaining 16 cases received antiplatelet drug combined with warfarin, but only 1 case achieved the target international standardized ratio of 1.5-2.5. Out of all 41 cases, only 1 case (2%) received standard antithrombotic treatment before MI onset. (4) Clinical symptoms of MI: at MI onset, 32 patients presented with different clinical symptoms, with typical MI symptoms such as chest tightness, chest pain, precordial discomfort in 18 cases, and cardiopulmonary arrest accompanied by syncope or convulsions in 10 cases. Other non-specific symptoms included abdominal pain, nausea, vomiting and pallor. Nine patients were asymptomatic and were found to have silent MI on follow-up. (5) ECG and imaging findings: ECG showed ST-T changes in 33 cases, and abnormal Q waves, and arrhythmias in the remaining patients; echocardiography indicated coronary artery aneurysm with thrombosis in 27 cases, reduced left ventricular ejection fraction in 18 cases, abnormal wall motion in 15 cases, and ventricular aneurysm in 3 cases. Thirty-seven patients underwent coronary angiography and (or) multi-slice spiral CT angiography, with 39 occluded vessels and 3 severe stenosis (≥75%), all of which were caused by giant aneurism with thrombus formation. (6) Treatment of MI: of the 32 patients with acute MI, 9 patients received successful cardiopulmonary resuscitation, 7 patients received intravenous thrombolysis, and 1 patient underwent percutaneous coronary balloon angioplasty. All of these patients received dual antiplatelet drugs and low-molecular-weight heparin at therapeutic doses following MI treatment. Sixteen patients received coronary artery bypass graft (CABG) treatment, all of which were successful. (7) Outcomes: the follow-up time was 994 (215, 1 832) d. Thirty-one patients showed improvement, 5 patients experienced disease progression or no change, 1 patient died, and 4 patients were lost to follow-up.Conclusions:MI in children with CAL after KD often occurs within 1 year after the onset of KD. MI can present with atypical clinical symptoms in children. CABG is the main treatment option in children severe CAL after KD who developed MI.
8.Relationship between clopidogrel resistance and genetic variability in Kawasaki disease children with coronary artery lesions
Yinyin CAO ; Qiyang PAN ; Jian LI ; Xiaofang ZHONG ; Xuecun LIANG ; Lan HE ; Chen CHU ; Quming ZHAO ; Lu ZHAO ; Feng WANG ; Shuna SUN ; Yixiang LIN ; Guoying HUANG ; Fang LIU
Chinese Journal of Pediatrics 2024;62(10):981-988
Objective:To analyze the distribution of clopidogrel metabolism-related gene variability in Kawasaki disease (KD) children with coronary artery lesions (CAL) across different age groups and the impact of genetic variability on the efficacy of clopidogrel antiplatelet therapy.Methods:A retrospective cohort study was conducted. Clinical data were collected from 46 KD children with CAL who were hospitalized in the Cardiovascular Center of Children′s Hospital of Fudan University between January 2021 and August 2022 and were treated with clopidogrel, including gender, age, body mass index, course of KD, CAL severity grade, and baseline platelet count. According to their age, the children were divided into ≥2-year-old group and <2-year-old group. Their platelet responsiveness was assessed by adenosine diphosphate-induced platelet inhibition rate (ADPi) calculated via thromboelastography, and children were categorized into high on-treatment platelet reactivity (HTPR) and normal on-treatment platelet reactivity (NTPR) groups. Genotypes of CYP2C19, PON1 and ABCB1 were detected. The t test, one-way analysis of variance and Chi-square test were used for intergroup comparison. Results:Among the 46 KD children with CAL, 34 were male and 12 were female; 37 were ≥2-year-old and 9 were <2-year-old; 25 cases were in the HTPR group and 21 cases were in the NTPR group, with 19 HTPR and 18 NTPR in the ≥2-year-old group, and 6 HTPR and 3 NTPR in the <2-year-old group. Genetic analysis showed that 92 alleles among the 46 children, with frequencies of CYP2C19*1, CYP2C19*2, CYP2C19*3, CYP2C19*17, PON1 192Q, PON1 192R, ABCB1 3435C, ABCB1 3435T at 59% (54/92), 32% (29/92), 9% (8/92), 1% (1/92), 36% (36/92), 64% (59/92), 63% (58/92) and 37% (34/92), respectively. Analysis of the impact of genotype on ADPi revealed that in children aged ≥2 years, those with CYP2C19*1/*3 genotype had significantly lower ADPi than those with CYP2C19*1/*1 genotype ((34±15)% vs. (61±29)%, t=2.18, P=0.036). There were also no significant difference in ADPi among children with PON1 192Q homozygous, PON1 192R heterozygote and PON1 192R homozygous genotypes ((40±22)% vs. (52±33)% vs. (65±27)%, F=2.17, P=0.130), or among those with ABCB1 3435C homozygous, ABCB1 3435T heterozygote and ABCB1 3435T homozygous genotypes ((55±34)% vs. (60±27)% vs. (49±24)%, F=0.33, P=0.719). In <2-year-old group, there were no significant differences in ADPi across CYP2C19*1/*1, CYP2C19*1/*2 and CYP2C19*2*2 genotypes ((40±20)% vs. (53±37)% vs. (34±16)%, F=0.37, P>0.05). There were no significant differences in ADPi across CYP2C19*1/*1 and CYP2C19*1/*3 genotypes ((44±27)% vs. (42±20)%, t=0.08, P>0.05). There were no significant differences in ADPi across PON1 192Q homozygous, PON1 192R heterozygote and PON1 192R homozygous genotypes (45% vs. (55±27)% vs. (24±5)%, F=1.83, P>0.05). There were no significant differences in ADPi across ABCB1 3435C homozygous, ABCB1 3435T heterozygote and ABCB1 3435T homozygous genotypes ((36±16)% vs. (50±35)% vs. 45%, F=0.29, P>0.05). The risk analysis of HTPR in different genotypes revealed that in children aged ≥2 years, carrying at least 1 or 2 loss-of-function alleles of CYP2C19 was a risk factor for HTPR ( OR=4.69, 10.00, 95% CI 1.11-19.83, 0.84-119.32, P=0.033, 0.046, respectively), and PON1 192R homozygosity and carrying at least one PON1 192R allele were protective factors against HTPR ( OR=0.08, 0.13, 95% CI 0.01-0.86, 0.01-1.19, P=0.019, 0.043, respectively). Conclusion:KD children aged ≥2 years carrying CYP2C19 loss-of-function alleles and PON1 192Q are more likely to develop HTPR.
9.Analysis of the Spatio-temporal Characteristics and Influencing Factors of Local Hospitalization Propor-tion of Guangdong Province
Shengliang CHEN ; Sihui JIN ; Dongbao ZHAO ; Kangmei KONG ; Renjia SHU ; Qiumao CAI ; Yixiang HUANG
Chinese Hospital Management 2024;44(1):23-27
Objective To analyze the spatio-temporal characteristics and influencing factors of local hospitalization proportion in 57 counties of Guangdong Province.Methods Using local hospitalization proportion and related indicators in 57 counties of Guangdong Province from 2016 to 2019,temporal trend analysis and spatial autocorrelation analy-sis were used to analyze the spatiotemporal characteristics.Bayesian spatio-temporal model was used to explore in-fluencing factors of local hospitalization proportion.Results The local hospitalization proportion in Guangdong Province rose from 79.8%in 2016 to 84.1%in 2019,showing an increasing trend and the overall characteristics of"high in the west and low in the east".The global and local spatial autocorrelation results show that there is a spatial correla-tion in the local hospitalization proportion within the counties of Guangdong Province,and spatial aggregation has formed in some areas.There is a"high"aggregation in western Guangdong,and a"low"aggregation in eastern Guangdong Province.The Bayesian spatio-temporal model shows that the number of people with a bachelor's de-gree or above per 1 000 population and the CMI of county hospitals had an effect on the local hospitalization propor-tion(P<0.05).Conclusion Guangdong Province can improve the medical service capacity of county hospitals sub-stantially and introduce or train high-quality talents through multiple measures,and continue to improve the local hospitalization proportion.
10.Structural repurposing of SGLT2 inhibitor empagliflozin for strengthening anti-heart failure activity with lower glycosuria.
Yixiang XU ; Chao ZHANG ; Kai JIANG ; Xinchun YANG ; Feng CHEN ; Zhiyang CHENG ; Jinlong ZHAO ; Jiaxing CHENG ; Xiaokang LI ; Xin CHEN ; Luoyifan ZHOU ; Hao DUAN ; Yunyuan HUANG ; Yaozu XIANG ; Jian LI
Acta Pharmaceutica Sinica B 2023;13(4):1671-1685
Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been reapproved for heart failure (HF) therapy in patients with and without diabetes. However, the initial glucose-lowering indication of SGLT2i has impeded their uses in cardiovascular clinical practice. A challenge of SGLT2i then becomes how to separate their anti-HF activity from glucose-lowering side-effect. To address this issue, we conducted structural repurposing of EMPA, a representative SGLT2 inhibitor, to strengthen anti-HF activity and reduce the SGLT2-inhibitory activity according to structural basis of inhibition of SGLT2. Compared to EMPA, the optimal derivative JX01, which was produced by methylation of C2-OH of the glucose ring, exhibited weaker SGLT2-inhibitory activity (IC50 > 100 nmol/L), and lower glycosuria and glucose-lowering side-effect, better NHE1-inhibitory activity and cardioprotective effect in HF mice. Furthermore, JX01 showed good safety profiles in respect of single-dose/repeat-dose toxicity and hERG activity, and good pharmacokinetic properties in both mouse and rat species. Collectively, the present study provided a paradigm of drug repurposing to discover novel anti-HF drugs, and indirectly demonstrated that SGLT2-independent molecular mechanisms play an important role in cardioprotective effects of SGLT2 inhibitors.

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