1.Advances in diffuse optical technology lenses for myopia control
Kun HE ; Bingxin PAN ; Suyun YANG ; Zhiyang HE ; Mengting ZHENG ; Meiling SHU ; Pengfei JIANG ; Shan XU ; Pengfei TIAN
International Eye Science 2025;25(9):1476-1483
Recent years have witnessed significant advancements in myopia control research through the application of diffuse optical technology(DOT)spectacle lenses. Myopia has emerged as a global public health challenge, affecting nearly half of the world's population, with childhood and adolescent myopia rates continuing to rise. DOT lenses represent an innovative myopia control intervention based on retinal contrast signal theory. These lenses incorporate micro-light scattering dots distributed across the lens surface to reduce retinal imaging contrast and modulate the influence of visual input on axial elongation, thereby slowing myopia progression. The core mechanism operates through refractive index differences between the lens substrate(1.53)and scattering dots(1.50), which generate optical scattering effects. This design maintains clear vision through a central 5 mm optical zone while effectively reducing contrast signal intensity in the peripheral retina. Large-scale randomized controlled trials, including the CYPRESS study, have demonstrated significant myopia control efficacy in children aged 6-10 years: 12-month follow-up data revealed a 74% reduction in myopia progression and a 50% reduction in axial elongation, with sustained safety and visual quality maintained over 4-year long-term follow-up. However, several aspects of DOT technology remain contentious and require further clinical validation, including its applicability across different age groups, optimal scattering dot density configurations, combined application effects with other myopia control methods, and long-term visual adaptation during extended use. This review systematically examines the theoretical foundations, design characteristics, clinical application progress, and future development directions of DOT technology, providing scientific evidence for clinical myopia prevention and control strategy formulation.
2.Photoaffinity probe-enabled discovery of sennoside A reductase in Bifidobacterium pseudocatenulatum.
Yang XU ; Shujing LV ; Xiang LI ; Chuanjia ZHAI ; Yulian SHI ; Xuejiao LI ; Zhiyang FENG ; Gan LUO ; Ying WANG ; Xiaoyan GAO
Journal of Pharmaceutical Analysis 2025;15(1):101108-101108
Sennoside A (SA), a typical prodrug, exerts its laxative effect only after its transformation into rheinanthrone catalyzed by gut microbial hydrolases and reductases. Hydrolases have been identified, but reductases remain unknown. By linking a photoreactive group to the SA scaffold, we synthesized a photoaffinity probe to covalently label SA reductases and identified SA reductases using activity-based protein profiling (ABPP). From lysates of an active strain, Bifidobacterium pseudocatenulatum (B. pseudocatenulatum), 397 proteins were enriched and subsequently identified using mass spectrometry (MS). Among these proteins, chromate reductase/nicotinamide adenine dinucleotide (NADH) phosphate (NADPH)-dependent flavin mononucleotide (FMN) reductase/oxygen-insensitive NADPH nitroreductase (nfrA) was identified as a potent SA reductase through further bioinformatic analysis and The Universal Protein Resource (UniProt) database screening. We also determined that recombinant nfrA could reduce SA. Our study contributes to further illuminating mechanisms of SA transformation to rheinanthrone and simultaneously offers an effective method to identify gut bacterial reductases.
3.Clinical Study on Shenshi Jiangzhuo Formula in Treating Non-Alcoholic Fatty Liver Disease with Phlegm Blended with Stasis Syndrome
Ziqi LIN ; Zheng XU ; Zhiyang HUANG ; Zheng WEN ; Fanwei WU
Journal of Guangzhou University of Traditional Chinese Medicine 2025;42(10):2451-2457
Objective To evaluate the clinical efficacy of Shenshi Jiangzhuo Formula(composed of Poria,Atractylodis Rhizoma,Magnoliae Officinalis Cortex,Pinelliae Rhizoma Praeparatum,Aurantii Fructus Immaturus,Arecae Semen,Talcum,Tetrapanacis Medulla,Notoginseng Radix et Rhizoma,Paeoniae Radix Rubra,Rubiae Radix et Rhizoma,Broussonetiae Fructus,etc.)in treating non-alcoholic fatty liver disease(NAFLD)with phlegm blended with stasis syndrome.Methods A total of 76 NAFLD patients with phlegm blended with stasis syndrome from the Seventh School of Clinical Medicine,Guangzhou University of Chinese Medicine(Shenzhen Bao'an Traditional Chinese Medicine Hospital)were enrolled between February 2024 and December 2024.The patients were randomly assigned(via random number table)to either the trial group(n=38,treated with Silibinin Meglumine Tablets plus Shenshi Jiangzhuo Formula)or the control group(n=38,treated with Silibinin Meglumine Tablets alone)for 8 weeks.The changes in liver controlled attenuation parameter(CAP),liver function markers[alanine aminotransferase(ALT),aspartate aminotransferase(AST),gamma-glutamyl transferase(GGT)],lipid profiles[triglycerides(TG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C)],and traditional Chinese medicine(TCM)syndrome scores were observed before and after treatment.Clinical efficacy and safety were evaluated.Results(1)One case dropped out from each group during the study and 37 cases in each group were included for final statistics.(2)After 8 weeks of treatment,the overall response rate in the trial group was 94.59%(35/37),compared with 62.16%(23/37)in the control group.Intergroup comparison revealed that the trial group demonstrated significantly superior overall therapeutic efficacy(by rank-sum test)and overall response rate(by chi-square test)compared with the control group(P<0.01).(3)Both groups showed improved CAP values after treatment,and the trial group demonstrated significantly greater improvement compared to the control group(P<0.01).(4)Post-treatment improvements in alanine aminotransferase(ALT),aspartate aminotransferase(AST),and gamma-glutamyl transferase(GGT)were improved in both groups(P<0.01),with the trial group showing significantly superior improvements(P<0.05 or P<0.01).(5)Triglycerides(TG),total cholesterol(TC),and low-density lipoprotein cholesterol(LDL-C)were improved in both groups after treatment,and the trial group exhibited significantly better outcomes(P<0.01).(6)Both groups presented reduced TCM syndrome scores after treatment,and the trial group showed greater reduction(P<0.01).(7)No significant adverse recations were observed in both groups,showing high safety.Conclusion Integrative therapy with Shenshi Jiangzhuo Formula exerts certain effects in improving CAP values,liver function,lipid metabolism,and TCM symptoms in NAFLD patients with phlegm blended with stasis syndrome,demonstrating robust clinical value.
4.Application of 3D printing technology in the adjuvant treatment of complex Stanford type B aortic dissection and abdominal aortic aneurysm
Guo XU ; Wei XIONG ; Shanglin BAI ; Xu WU ; Qi XIONG ; Liangxin ZHAO ; Zhiyang XIONG
Journal of Interventional Radiology 2025;34(9):943-949
Objective To discuss the application of 3D printing technology in the adjuvant treatment of complex Stanford type B aortic dissection(SBAD)and abdominal aortic aneurysm.Methods The clinical data of 64 patients with complex SBAD and 64 patients with abdominal aortic aneurysm,who were admitted to the Mianyang No.404 Hospital of China from January 2022 to January 2024,were retrospectively analyzed.Of the 64 patients with complex SBAD,33 received preoperative 3D printing adjuvant treatment(observation group Ⅰ)and 31 received preoperative routine examination(control group Ⅰ).Of the 64 patients with abdominal aortic aneurysm,32 received preoperative 3D printing adjuvant treatment(observation group Ⅱ)and 32 received preoperative routine examination(control group Ⅱ).The changes in left-right diameter(LR)and anterior-posterior diameter(AP)of anatomical structure in observation group Ⅰ and observation group Ⅱ were analyzed.The perioperative situations were compared between observation group Ⅰ and control group Ⅰ,as well as between observation groupⅡ and control group Ⅱ.Results In patients with complex SBAD,LR of descending aorta diaphragm in S2(STL model)was significantly higher than that in S1(CTA image)and S3(plastic model,P<0.05),and AP of descending aorta diaphragm in S2 was higher than that in S3(P<0.05).LR of brachiocephalic trunk in S3 was significantly lower than that in S1 and S2(P<0.05),AP of brachiocephalic trunk in S3 stage was significantly higher than that in S1 and S2(P<0.05),and AP of brachiocephalic trunk in S2 was higher than that in S1(P<0.05).LR of left common carotid artery in S3 was significantly higher than that in S1 and S2(P<0.05),LR of left common carotid artery in S2 was higher than that in S1(P<0.05),and AP of left common carotid artery in S3 was lower than that in S1(P<0.05).LR and AP of left subclavian artery in S3 were significantly higher than those in S1 and S2(P<0.05).In patients with abdominal aortic aneurysm,LR and AP of tumor neck in S3 were significantly higher than those in S1(P<0.05),and AP of aneurysm neck in S3 was significantly higher than that in S2(P<0.05).LR and AP of aneurysm in S3 and S2 were significantly higher than those in S1(P<0.05),and LR and AP of aneurysm in S3 were significantly higher than those in S2(P<0.05).LR of abdominal aortic bifurcation in S3 and S2 was significantly higher than that in S1(P<0.05),LR of abdominal aortic bifurcation in S3 was significantly higher than that in S2(P<0.05),and AP of abdominal aortic bifurcation in S3 was significantly lower than that in S1(P<0.05).AP of left common iliac artery in S3 was significantly lower than that in S1(P<0.05).In the observation group Ⅰ,the operation time,endovascular operation time and length of hospital stay were significantly shorter than those in the control group Ⅰ(P<0.05),and the intraoperative blood loss and used dosage of contrast agent were lower than those in the control group Ⅰ(P<0.05).In observation group Ⅱ,the operation time,endovascular operation time and length of hospital stay were significantly shorter than those in the control group Ⅱ(P<0.05),and the intraoperative blood loss and used dosage of contrast agent were lower than those in the control group Ⅱ(P<0.05).In patients with complex SBAD or abdominal aortic aneurysm,there was no internal leakage or stent displacement at 6 months after surgery.Conclusion Adjuvant treatment with 3D printing technology is helpful for improving anatomical structure measurement of lesion sites in patients with complex SBAD and abdominal aortic aneurysm.Preoperative 3D plastic model preview surgery is helpful for shortening the operation time and length of hospital stay and reducing the used dosage of contrast agent without affecting surgical treatment effect.
5.Inhibitory effects of Ginkgo biloba extract on renal inflammation in diabetic nephropathy model mice and its mechanism
Jing CHEN ; Xiaoyi YANG ; Jing CHEN ; Xin SHAN ; Jie WANG ; Huiqin XU ; Zhiyang LYU
China Pharmacy 2024;35(2):186-191
OBJECTIVE To investigate the inhibitory effects of Ginkgo biloba extract (GBE) on renal inflammation in diabetic nephropathy (DN) model mice, and its potential mechanism. METHODS KK/Ay mice were fed with high fat and high sugar to induce DN model. They were divided into model group, positive control group [metformin 200 mg/(kg·d)], GBE low-dose and high-dose groups [100, 200 mg/(kg·d)], with 6 mice in each group. Six C57BL/6J mice were fed with a regular diet as the control group. Administration groups were given relevant liquid intragastrically, control group and model group were given constant volume of normal saline intragastrically, once a day, for 8 consecutive weeks. The body weight, fasting blood glucose, 24-hour food intake, 24-hour urine output, monocyte chemoattractant protein-1 (MCP-1), interleukin-12 (IL-12), IL-10, advanced glycation end products (AGEs), blood urea nitrogen (BUN) and serum creatinine (Scr) of mice were measured, and the ratio of bilateral kidneys to body weight was also calculated. The pathological injury and fibrotic changes of the renal cortex were observed, and the expressions of macrophage polarization marker proteins [type M1: inducible nitric oxide synthase (iNOS); type M2: arginase-1 (Arg-1)] and AGEs-the receptor of advanced glycation end products (RAGE)/Ras homolog gene pharm_chenjing@163.com family member A (RhoA)/Rho-associated coiled-coil forming protein kinase (ROCK) signaling pathway-related proteins were determined in renal cortex. RESULTS Compared with the model group, the symptoms such as renal cortical hyperplasia, vacuoles, infiltration of inflammatory cells, and renal cortical fibrosis had been improved in GBE low-dose and high-dose groups; body weight, serum level of IL-10, the expression of Arg-1 in the renal cortex were significantly higher than model group (P< 0.01); fasting blood glucose, 24-hour food intake, 24-hour urine output, serum levels of MCP-1, IL-12, BUN, Scr and AGEs, the ratio of bilateral kidneys to body weight, renal injury score, the proportion of renal interstitial fibrosis, the protein expressions of iNOS, RAGE, RhoA and ROCK1 (except for GBE low-dose group) in renal cortex were significantly lower than model group (P<0.01). CONCLUSIONS GBE could improve kidney damage and alleviate inflammatory response in DN model mice, the mechanism of which may be related to inhibiting the AGEs-RAGE/RhoA/ROCK signaling pathway and regulating macrophage polarization.
6.Surgical strategy for lumbar degenerative diseases with segment instability between upper instrument vertebra and adjacent upper vertebra
Xi LI ; Lei LIU ; Zhe ZHANG ; Yuzhu XU ; Peiyang WANG ; Xiaolong LI ; Guozhen LIU ; Lele ZHANG ; Zhiyang XIE ; Yuao TAO ; Pan FAN ; Yuntao WANG
Chinese Journal of Orthopaedics 2024;44(10):658-668
Objective:To summarize long-term clinical follow-up results of segment instability between the upper instrumented vertebra (UIV) and the adjacent upper vertebra (UIV+1) and to establish the optimal timing for surgery for UIV+1.Methods:A retrospective analysis was conducted on 265 patients with lumbar degenerative diseases who underwent transforaminal lumbar interbody fusion (TLIF) surgery at the Department of Spinal Surgery, Zhongda Hospital, from January 2014 to December 2018. The cohort included 119 male and 146 female patients, with an average age of 64.93 years (range: 32-86 years). Preoperative dynamic imaging measured sagittal angulation (SA) and sagittal translation (ST) of the UIV+1/UIV segment. Patients with SA>10° or ST>2 mm were categorized into the unstable group, further divided into the unstable non-fusion group and the unstable fusion group based on whether UIV+1 expansion fusion was performed. The remaining patients were classified into the stable group. Imaging indicators, Visual Analogue Scale (VAS) scores, Oswestry disability index (ODI) scores, and Japanese Orthopaedic Association (JOA) scores were compared among the groups, with JOA improvement rates calculated to assess clinical efficacy. Pearson correlation coefficient analysis was employed to examine correlations between preoperative imaging indicators and final follow-up JOA improvement rates. Receiver Operating Characteristic (ROC) curves and the maximum Youden index were utilized to determine thresholds for preoperative SA and ST.Results:The follow-up duration for all patients was 73.53±12.92 months (range: 61-108 months). The stable group (124 cases) included 61 males and 63 females, aged 64.31±9.83 years (range: 44-82 years). The unstable non-fusion group (59 cases) included 22 males and 37 females, aged 65.76±11.01 years (range: 32-86 years). The unstable fusion group (82 cases) included 36 males and 46 females, aged 65.26±8.68 years (range: 47-80 years). At the last follow-up, the unstable non-fusion group exhibited ΔSA 0.90°±1.97° and ΔST 0.77±1.27 mm, both significantly higher than the stable group's ΔSA 0.25°±1.57° and ΔST 0.34±0.34 mm ( t=3.564, P<0.001; t=2.311, P=0.022). Clinical improvements were lower in the unstable non-fusion group compared to the other two groups: VAS (2.28±0.83), ODI (5.91%±3.46%), JOA (24.11±1.78), with a JOA improvement rate of 60%. The stable group showed VAS (1.51±0.69), ODI (3.71%±1.75%), JOA (27.33±1.91), with a JOA improvement rate of 83%. The unstable fusion group had VAS (1.46±0.83), ODI (3.46%±1.81%), JOA (26.48±1.66), with a JOA improvement rate of 78%. These differences were statistically significant ( F=32.117, P<0.001; F=24.827, P<0.001; F=92.658, P<0.001; F=93.341, P<0.001). The JOA improvement rate was negatively correlated with preoperative SA ( r=-0.363, P<0.001) to a low extent, and with preoperative ST ( r=-0.596, P<0.001) to a moderate extent. ROC curve analysis determined the preoperative SA threshold as 11.5° and the preoperative ST threshold as 1.85 mm. Conclusion:Pre-existing instability of the responsible segment UIV and UIV+1 (SA>10° or ST>2 mm) may worsen during long-term follow-up after TLIF. When preoperative SA exceeds 11.5° and ST exceeds 1.85 mm between UIV and UIV+1, performing an extended fusion involving UIV+1 can ensure surgical efficacy over long-term follow-up.
7.The clinical value of matrix metalloproteinase-3 combined with anti-mutant citrulline vimentin antibody and rheumatoid factor in the diagnosis of rheumatoid arthritis
Nan ZHANG ; Man LI ; Ting XIA ; Zhiye XU ; Zhiyang LI
Journal of Chinese Physician 2024;26(11):1681-1686
Objective:To investigate the diagnostic value of serum matrix metalloproteinase 3 (MMP-3) combined with anti-mutant citrulline vimentin antibody (anti-MCV) and rheumatoid factor (RF) in rheumatoid arthritis (RA).Methods:A retrospective study was conducted to select 78 patients diagnosed with RA, 30 with Sjogren′s syndrome (SS), 25 with connective tissue disease (CTD), and 38 with antiphospholipid syndrome (APS) from the Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University from August 2022 to April 2024. In the same period, 50 healthy controls were selected from the physical examination center of our hospital. Fasting peripheral blood RF, anti-streptolysin O (ASO), C-reactive protein (CRP), erythrocyte deposition rate (ESR), interleukin-6 (IL-6), procalcitonin (PCT), anti-keratin antibody (AKA), anti-MCV, MMP-3, anti-cyclic citrullinated peptide (anti-CCP) level. Fasting peripheral blood MMP-3 levels in SS, CTD, APS patients and healthy control group were compared, Spearman correlation analysis was used to evaluate the correlation between MMP-3 levels and various indicators, and logistic regression analysis was used to screen the related influencing factors of RA occurrence. The diagnostic value of serum MMP-3, anti-MCV, RF and combined detection for RA was evaluated by receiver operating characteristic (ROC) curve.Results:There were statistically significant differences in RF, CRP, ESR, IL6, AKA, antiMCV, MMP-3 and anti-CCP between RA group and healthy control group (all P<0.001), while there were no statistically significant differences in PCT and ASO between the RA group and the healthy control group (all P>0.05). Serum MMP-3 level in the RA group was significantly higher than that in SS, CTD, APS and healthy control group, and the difference was statistically significant (all P<0.05). MMP-3 was positively correlated with anti-CCP, CRP, ESR, anti-MCV, RF and AKA ( r=0.403, 0.532, 0.530, 0.431, 0.427, 0.391, all P<0.05). Multivariate logistic regression analysis showed that MMP-3 ( OR=1.082, P=0.02), anti-MCV ( OR=1.015, P=0.049) and RF ( OR=1.046, P=0.036) were independent risk factors for RA. ROC curve showed that when the cut-off value of MMP-3 was 53.10 ng/ml, the area under the curve for diagnosing RA was 0.889, the sensitivity was 74.5%, and the specificity was 96.0%. The area under ROC curve of MMP-3 combined with anti-MCV and RF for the diagnosis of RA was 0.975, the sensitivity was 88.2%, and the specificity was 99.7%. Conclusions:MMP-3 has a certain value in the differential diagnosis of RA, and MMP-3 combined with anti-MCV and RF is of great significance in the auxiliary diagnosis of RA.
8.Study on the assessment of application value of CT equipment from multi-dimension based on real world data
Zhiyang XU ; Yuzhi YANG ; Jian CHEN ; Chundong QIU
China Medical Equipment 2024;21(8):13-17
Objective:To assess the values of computed tomography(CT)equipment in whole life cycle and operation status from multi-dimension based on real world data,and to quantify the performance,operation status,and benefit analysis of medical equipment,so as to assist to grasp the operation status of CT equipment for hospital.Methods:Depended on the viewpoint of real-world data,economic benefits,metrology and performance data of 5 pieces of CT equipment,which included type A,type B,type C,type D and type E,used in hospitals in the last 4 years were collected.Type A,type B and type C were all imported CT equipment,and type A and type B were the same model.Both type D and type E were domestic CT equipment.The analytic hierarchy process(AHP)was used to assign the weights of each data,and form effectively multi-dimensional evaluation system.Results:The value of consistency ratio(CR)of the hierarchical weight allocation matrix was 0.042 that was less than 0.1,which met the requirement of consistency test.The scores of the comprehensive values the 5 pieces of CT equipment of type A,type B,type C,type D and type E were respectively 68.10,30.35,39.50,60.99 and 39.76.There was a significant difference between the two pieces of imported CT equipment of type A and type B of the same model in different use environments.The score of type D of domestic CT equipment was higher than those of the type B and type C of imported CT equipment,respectively.Conclusion:Under suitable use environments,domestic CT equipment can replace imported equipment.The AHP method can be used in the assessment of CT equipment value.
9.Risk factors of hepatocellular carcinoma to TACE refractoriness
Zhiyang PAN ; Wei XU ; Maoheng ZU ; Hao XU ; Yong WANG ; Yan LI ; Zhongkai WANG ; Xiaoyang XU
Chinese Journal of Hepatobiliary Surgery 2023;29(1):34-37
Objective:To study the risk factors of patients with hepatocellular carcinoma (HCC) to transcatheter arterial chemoembolization(TACE) refractoriness.Methods:The clinical data of 106 HCC patients who underwent TACE at the Affiliated Hospital of Xuzhou Medical University from January 2020 to December 2021 were retrospectively studied. There were 90 males and 16 females, with the age of (59.9±9.3) years. These patients were divided into the TACE-refractory group ( n=47) and the control group ( n=59) based on whether TACE refratoriness occurred after surgery. Serum alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist-II (PIVIKA-II), maximum diameter of tumor, number of tumor and tumor vascularization patterns between the two groups were compared. Multivariate logistic regression analysis was performed to analyse the risk factors of TACE refractoriness in patients with HCC after TACE. Results:The proportion of patients with AFP >400 μg/L, PIVIKA-II >40 AU/L, number of tumor and tumor vascularization patterns Ⅲ+ Ⅳ (uneven enhancement) were significantly higher in the TACE-refractory group than the control group (all P<0.05). The maximum diameter of tumor for patients in the TACE-refractory group was significantly larger than that in the control group ( Z=-2.41, P=0.016). Multivariate logistic regression analysis showed that patients with serum AFP >400 μg/L( OR=2.707, 95% CI: 1.008-7.271), multiple tumors ( OR=6.069, 95% CI: 2.115-17.415) and tumor vascularization patterns Ⅲ+ Ⅳ (uneven enhancement)( OR=7.813, 95% CI: 2.246-27.176) before the first TACE were at increased risks of TACE refractoriness (all P<0.05). Conclusion:Preoperative AFP >400 μg/L, multiple tumors and tumor vascularization patterns Ⅲ+ Ⅳ were independent risk factors for TACE refractoriness in patients with HCC.
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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