1.Clinical Research on Guizhi Fulingwan in Treatment of Ovarian Cancer: A Review
Muxin GUAN ; Jiaxing FENG ; Mengyi ZHU ; Yu WANG ; Xiaoke WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):296-303
Ovarian cancer (OC) is a common gynecological malignant tumor in clinical practice. In the early stage,it is often asymptomatic,while in the late stage,it mainly presents with non-specific symptoms such as abdominal distension,poor appetite,and dull abdominal pain. Some patients may also have cachexia such as weight loss and anemia. Early diagnosis is difficult,and the mortality rate ranks first among gynecological malignant tumors,making OC a major challenge in clinical treatment. The classic Chinese medicine formula Guizhi Fulingwan comes from the Jingui Yaolue and has the effects of promoting blood circulation,removing blood stasis,and reducing abdominal lumps. In recent years,it has been widely used to treat OC with good results. This article summarized the clinical application of Guizhi Fulingwan in the treatment of OC from two aspects:The analysis of its basic prescriptions and clinical research. In terms of basic prescriptions,the formula has the ability to promote blood circulation,remove blood stasis,and reduce abdominal lumps. It can exert therapeutic effects considering both water and blood aspects and reduce abdominal lumps, with characteristics of simultaneous Yang warming and heat clearing and parallel supplementation and elimination. Through the methods of "circulation" and "supplementation", it strengthens the body,dispels evil,and eliminates underlying symptoms. In clinical studies,Guizhi Fulingwan can be applied to various stages of patients with OC,which not only promotes the recovery of the body after OC surgery but also can be combined with chemotherapy and immunotherapy to synergistically treat advanced OC and enhance treatment efficacy. In addition,the formula can also alleviate various adverse reactions caused by chemotherapy,with high safety,improve patients' quality of life,prolong survival,and optimize tumor control effects. Based on the above analysis,this article elaborated on the current clinical research status of Guizhi Fulingwan combined with Western medicine in the treatment of OC and proposed suggestions and improvements to address the shortcomings in current clinical research,so as to provide reference for the clinical application of this formula in the treatment of OC and the construction of a combined traditional Chinese and Western medicine treatment model.
2.Clinical Research on Guizhi Fulingwan in Treatment of Ovarian Cancer: A Review
Muxin GUAN ; Jiaxing FENG ; Mengyi ZHU ; Yu WANG ; Xiaoke WU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):296-303
Ovarian cancer (OC) is a common gynecological malignant tumor in clinical practice. In the early stage,it is often asymptomatic,while in the late stage,it mainly presents with non-specific symptoms such as abdominal distension,poor appetite,and dull abdominal pain. Some patients may also have cachexia such as weight loss and anemia. Early diagnosis is difficult,and the mortality rate ranks first among gynecological malignant tumors,making OC a major challenge in clinical treatment. The classic Chinese medicine formula Guizhi Fulingwan comes from the Jingui Yaolue and has the effects of promoting blood circulation,removing blood stasis,and reducing abdominal lumps. In recent years,it has been widely used to treat OC with good results. This article summarized the clinical application of Guizhi Fulingwan in the treatment of OC from two aspects:The analysis of its basic prescriptions and clinical research. In terms of basic prescriptions,the formula has the ability to promote blood circulation,remove blood stasis,and reduce abdominal lumps. It can exert therapeutic effects considering both water and blood aspects and reduce abdominal lumps, with characteristics of simultaneous Yang warming and heat clearing and parallel supplementation and elimination. Through the methods of "circulation" and "supplementation", it strengthens the body,dispels evil,and eliminates underlying symptoms. In clinical studies,Guizhi Fulingwan can be applied to various stages of patients with OC,which not only promotes the recovery of the body after OC surgery but also can be combined with chemotherapy and immunotherapy to synergistically treat advanced OC and enhance treatment efficacy. In addition,the formula can also alleviate various adverse reactions caused by chemotherapy,with high safety,improve patients' quality of life,prolong survival,and optimize tumor control effects. Based on the above analysis,this article elaborated on the current clinical research status of Guizhi Fulingwan combined with Western medicine in the treatment of OC and proposed suggestions and improvements to address the shortcomings in current clinical research,so as to provide reference for the clinical application of this formula in the treatment of OC and the construction of a combined traditional Chinese and Western medicine treatment model.
3.Diagnostic value of hs-CRP and PCT combined with IL-6 in children with severe hand-foot-mouth disease
Lijun LUO ; Chenggao XU ; Fei SUN ; Xiaohui GAO ; Shunfeng MAO ; Xiaoping LU ; Junjie FENG
China Modern Doctor 2024;62(5):16-19
Objective To investigate the diagnostic value and clinical significance of hypersensitive C-reactive protein(hs-CRP),procalcitonin(PCT)combined with interleukin-6(IL-6)in children with severe hand-foot-mouth disease.Methods A total of 62 children hospitalized in our hospital from January 2022 to December 2022 were collected as research objects.According to the severity of infection,they were divided into observation group(severe infection group)with 29 cases and control group(mild infection group)with 33 cases.The differences of general data,total leukocyte count,neutrophil count,lymphocyte count,platelet count,hs-CRP,PCT,IL-6 and creatine kinase isoenzyme(CK-MB)between the two groups and their clinical applications were analyzed and compared.Results The total white blood cell count,neutrophil count,lymphocyte count,hs-CRP,PCT and IL-6 in the observation group were higher than those in the control group,and the difference has statistically significant.Receiver operator characteristic(ROC)curve analysis of hs-CRP predicted the sensitivity and specificity of severe infection of hand-foot-mouth disease were 79.3%and 93.9%(95%CI:0.852-10.985,P<0.05);The sensitivity and specificity of PCT were 93.1%and 84.8%(95%CI:0.907-1,P<0.05);The sensitivity and specificity of IL-6 were 96.6%and 87.9%(95%CI:0.945-1,P<0.05).Conclusions In hand-foot-mouth classification,PCT and IL-6 are highly sensitive.Although hs-CRP is less sensitive than the former,its specificity is higher than the former.Therefore,the combination of hs-CRP,PCT and IL-6 has higher value for hand-foot-mouth classification.
4.FGF21 regulates liver cell lipid metabolism through the SOCS3/JAK/STAT pathway
Fangfang SHEN ; Feng ZHU ; Ke XU ; Yiqun TENG
China Modern Doctor 2024;62(9):12-16
Objective By knocking down the expression of fibroblast growth factors 21(FGF21)in adipose liver cells,to observe lipid metabolism and to explore the molecular mechanism of FGF21 regulating lipid metabolism in liver cells.Methods By interfering with lentivirus transfection through FGF21,the expression of FGF21 was reduced in HepG2 cells.HepG2 cells were transfected with an empty vector as a control,and were respectively referred to as interference group and control group.Both groups were stimulated with palmitic acid oleic acid to construct non-alcoholic fatty liver disease(NAFLD)cell model.The expression of FGF21 was interfered by lentivirus vector,oil red O staining and spectrophotometric value were measured to observe the lipid deposition in cells.Use Western blot method to detect the changes of suppressor of cytokine signaling 3(SOCS3),JAK2,and STAT3 proteins in fatty liver cells.Results Oil red O staining and absorbance values showed that compared with control group,interference group significantly reduced the lipid droplet content in liver cells;Western blot results showed that the expression levels of suppressor of cytokine signaling 3(SOCS3),Janus kinase 2(JAK2),signal transducer and activator of transcription 3(STAT3),and STAT3 protein were significantly increased in interference group of liver cells.Conclusion In the fatty liver cell model,knocking down FGF21 can improve lipid deposition through liver cells.The mechanism may be through increasing the SOCS3/JAK/STAT pathway,but the specific mechanism of action needs further in-depth research in the future.
5.Clinical diagnosis and treatment analysis of 38 cases of primary parapharyngeal space tumors
Jiaxing LIAO ; Huajun FENG ; Jiangxue LIAO ; Qixu LIANG ; Gang QIN
Chinese Archives of Otolaryngology-Head and Neck Surgery 2024;31(4):205-209
OBJECTIVE To explore the clinical features and surgical treatment methods of primary parapharyngeal space tumors.METHODS The clinical data of 38 patients with primary parapharyngeal space tumors who were treated in the Affiliated Hospital of Southwest Medical University from June 2005 to April 2023 were retrospectively analyzed,and their clinical manifestations,imaging data,surgical methods,postoperative complications,postoperative pathological types and prognosis were analyzed.RESULTS The clinical manifestations of 38 patients were mainly pharyngeal discomfort and pharyngeal distension.CT and MRI can determine the size,location,and relationship of the tumor to surrounding tissue.The surgical methods included transcervical approach in 17 cases,transoral approach in 15 cases,transcervical-transparotid approach in 4 cases,and transcervical-transmandibular approach in 2 cases.Postoperative pathology diagnosed 28 cases(73.7%)of benign tumors and 10 cases(26.3%)of malignant tumors.After the postoperative follow-up of 2 months-17 years,there was no recurrence of benign tumor patients,and patients with malignant tumors survived well after comprehensive treatment with surgery and radiotherapy and chemotherapy.CONCLUSION Most patients with primary parapharyngeal space tumors have no specific clinical symptoms,and the types of pathologies are diverse.Choosing the appropriate surgical approach to remove the tumor is key to treatment.Neurologic deficits are the most important postoperative complication.Patients with benign tumors have good long-term effects after surgery,and patients with malignant tumors have better efficacy in the combination of surgery and chemoradiotherapy.
6.Visual analysis of research hotspots and trends in renal cell carcinoma targeted therapy based on VOSviewer software
Yayun WU ; Guizhi LI ; Sanli FENG ; Mingjin SHE ; Jiaxing MA
Journal of Clinical Medicine in Practice 2024;28(18):27-33
Objective To conduct a visual analysis of the current status, hotspots, and frontiers of research on renal cell carcinoma targeted therapy using VOSviewer software. Methods Literature related to renal cell carcinoma targeted therapy published between January 1, 2006 and December 31, 2023, from the Web of Science (WOS) Core Collection database were retrieved. Eligible articles were screened and subjected to bibliometric and visual analysis using VOSviewer software. Results A total of 1, 009 articles were selected, with an overall increasing trend in annual publication volume. The top three countries in terms of publication output were the United States, China, and Italy, while the top three institutions were Harvard University, The University of Texas, and France Uni-cancer Institute. The analysis of the core author collaboration network revealed close collaboration among researchers in the United States and the United Kingdom, whereas collaboration between China and foreign countries was limited, resulting in a relatively loose collaboration network. Through co-occurrence clustering analysis of high-frequency author keywords, nine clusters were generated, with hotspots focusing on targeted and immune combination therapy, efficacy, prognosis, drug resistance, targets, and biomarkers. Conclusion Remarkable progress has been made in renal cell carcinoma targeted therapy research over the past decade; however, drug resistance and adverse reactions to targeted therapies remain challenges in clinical treatment. Research related to targeted drug resistance mechanisms, novel targeted drugs, and effective predictive biomarkers has significantly increased. Grasping the developmental trends in this fieldis crucial, and VOSviewer's visual analysis can offer an intuitive representation of the current status, hotspots, and frontiers, thereby providing researchers with a valuable reference.
7.Clinical efficacy of analysis of modified biliary-intestinal anastomosis by pancreaticoduodenec-tomy and influencing factors of postoperative biliary leakage
Jingrui YANG ; Rui XIAO ; Lu WANG ; Jiaxing WANG ; Shaojie LIU ; Xiaodong ZHANG ; Zefeng WANG ; Xuemin FENG ; Junhua JIN ; Jianjun REN
Chinese Journal of Digestive Surgery 2023;22(5):642-649
Objective:To investigate the clinical efficacy of modified biliary-intestinal anasto-mosis by pancreaticoduodenectomy and influencing factors of postoperative biliary leakage.Methods:The propensity score matching and retrospective cohort study was conducted. The clinicopatholo-gical data of 165 patients with benign and malignant diseases around the ampullary who underwent pancreaticoduodenectomy in the Affiliated Hospital of Inner Mongolia Medical University from June 2014 to October 2020 were collected. There were 92 males and 73 females, aged (59±10)years. Of the 165 patients, 44 patients undergoing modified biliary-intestinal anastomosis within pancreatico-duodenectomy were divided into the modified group, and 121 patients undergoing traditional biliary-intestinal anastomosis within pancreaticoduodenectomy were divided into the traditional group. Observation indicators: (1) propensity score matching and comparison of general data of patients between the two groups after matching; (2) intraoperative and postoperative situations; (3) analysis of influencing factors of biliary leakage after pancreaticoduodenectomy. Propensity score matching was done by the 1:1 nearest neighbor matching method, with the caliper setting as 0.05. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Univariate analysis was conducted using the corresponding statistical methods based on data type. All indicators in univariate analysis were included in multivariate analysis. Multivariate analysis was conducted using the Logistic regression model. Results:(1) Propensity score matching and comparison of general data of patients between the two groups after matching. Of the 165 patients, 72 cases were successfully matched, including 36 cases in the modified group and 36 cases in the traditional group, respectively. The elimination of jaundice, preoperative reduction of jaundice and hypertension confounding bias ensured comparability between the two groups after propensity score matching. (2) Intraoperative and postoperative situations. All patients in the two groups underwent surgery successfully. The operation time, postoperative pathological type (lower bile duct cancer, pancreatic head cancer, pancreatic cystic tumor, chronic pancreatitis, duodenal cancer), time of no drainage fluid in the drainage tube around biliary-intestinal anastomosis were 371(270,545)minutes, 6, 12, 1, 2, 15, (12±7)days in patients of the modified group, versus 314(182,483) minutes, 13, 14, 1, 4, 4, (16±8)days in patients of the traditional group, showing significant differences in the above indicators between the two groups ( Z=-3.54, χ2=10.01, t=-2.34, P<0.05). Cases with postoperative grade A biliary leakage was 0 in patients of the modified group, versus 6 in patients of the traditional group, showing a significant difference between the two groups ( P<0.05). Cases with postoperative grade B biliary leakage, cases with postoperative grade B pancreatic fistula, cases with postoperative bleeding, cases with abdominal infection, cases with incision infection, cases with delayed gastric emptying, cases undergoing unplanned readmission were 1, 0, 1, 4, 1, 5, 1 in patients of the modified group, versus 0, 1, 2, 5, 2, 5, 2 in patients of the traditional group, showing no significant difference in the above indicators between the two groups ( P>0.05). Cases with postoperative grade A pancreatic fistula, cases with overall complications, cases with Clavien-Dindo grade Ⅰ-Ⅱ complications, cases with Clavien-Dindo grade Ⅲ-Ⅳ complications were 6, 12, 6, 6 in patients of the modified group, versus 7, 14, 8, 6 in patients of the traditional group, showing no significant difference in the above indicators between the two groups ( χ2=0.09, 0.24, 0.36, 0.00, P>0.05). None of patient in the two groups had postoperative grade C biliary leakage and postoperative grade C pancreatic fistula. (3) Analysis of influencing factors of biliary leakage after pancreaticoduodenectomy. Results of multivariate analysis showed that preoperative reduction of jaundice and traditional biliary-intestinal anastomosis were independent risk factors for biliary leakage after pancreaticoduodenectomy ( odds ratio=11.37, 12.27, 95% confidence interval as 1.76-73.35, 1.14-131.23, P<0.05). Conclusions:Compared with traditional biliary-intestinal anastomosis, modified biliary-intestinal anastomosis within pancreaticoduodenectomy is safe and feasible. Preoperative reduction of jaundice and traditional biliary-intestinal anastomosis are independent risk factors for biliary leakage after pancreaticoduodenectomy.
8.Analysis of the causes and clinical results of vertebral fracture during oblique lateral lumbar interbody fusion.
Zhong-You ZENG ; Xing ZHAO ; Yu ZHANG ; Ping-Quan CHEN ; Wei YU ; Yong-Xing SONG ; Shun-Wu FAN ; Fei PEI ; Shi-Yang FAN ; Guo-Hao SONG ; Hai-Feng WANG
China Journal of Orthopaedics and Traumatology 2023;36(5):406-413
OBJECTIVE:
To analyze the causes of vertebral fracture during oblique lateral interbody fusion in the treatment of lumbar spondylopathy, summarize the clinical results, and propose preventive measures.
METHODS:
Retrospective analysis was made on the data of 8 cases of lumbar spondylopathy and vertebral fracture treated by oblique lateral interbody fusion in three medical centers from October 2014 to December 2018. All were female, aged from 50 to 81 years with an average of 66.4 years. Disease types included 1 case of lumbar degenerative disease, 3 cases of lumbar spinal stenosis, 2 cases of lumbar degenerative spondylolisthesis and 2 cases of lumbar degenerative scoliosis. Preoperative dual energy X-ray bone mineral density test showed that 2 cases had T-value >-1 SD, 2 cases had T-value -1 to -2.5 SD, and 4 cases had T-value <-2.5 SD. Single segment fusion was in 5 cases, two segment fusion in 1 case and three segment fusion in 2 cases. Four cases were treated with OLIF Stand-alone and 4 cases were treated with OLIF combined with posterior pedicle screw fixation. Postoperative imaging examination showed vertebral fracture, and all of them were single vertebral fracture. There were 2 cases of right lower edge fracture of upper vertebral body at fusion segment, 6 cases of lower vertebral body fracture at fusion segment, and 6 cases with endplate injury and fusion cage partially embedded in vertebral body. Three cases of OLIF Stand-alone were treated with pedicle screw fixation via posterior intermuscular approach, while one case of OLIF Stand-alone and four cases of OLIF combined with posterior pedicle screw fixation were not treated specially.
RESULTS:
The 5 cases of initial operation and 3 cases of reoperation did not show wound skin necrosis or wound infection. The follow-up time was from 12 to 48 months with an average of 22.8 months. Visual analogue scale (VAS) of low back pain was preoperative decreased from 4 to 8 points (averagely 6.3 points) and postoperative 1 to 3 points (averagely 1.7 points) at the final follow-up. Oswestry disability index (ODI) was preoperative 39.7% to 52.4% (averagely 40.2%), and postoperative 7.9% to 11.2% (averagely 9.5%) at the final follow-up. During the follow-up, there was no loosening or fracture of the pedicle screw system, and no lateral displacement of the fusion cage;however, the fusion cage at the vertebral fracture segment had obvious subsidence. The intervertebral space height of vertebral fracture segment was preoperaive 6.7 to 9.2 mm (averagely 8.1 mm), and postoperative 10.5 to 12.8 mm (averagely 11.2 mm). The improvement rate after operation was 37.98% compared to preoperative. The intervertebral space height at final follow-up was 8.4 to 10.9 mm (averagely 9.3 mm), and the loss rate was 16.71% compared with that after operation. At the final follow-up, interbody fusion was achieved in all cases except for one that could not be identified.
CONCLUSION
The incidence of vertebral fracture during oblique lateral interbody fusion in the treatment of lumbar spondylopathy is lower, and there are many reasons for fracture, including preoperative bone loss or osteoporosis, endplate injury, irregular shape of endplate, excessive selection of fusion cage, and osteophyte hyperplasia at the affected segment. As long as vertebral fracture is found in time and handled properly, the prognosis is well. However, it still needs to strengthen prevention.
Humans
;
Female
;
Male
;
Spinal Fractures/surgery*
;
Retrospective Studies
;
Treatment Outcome
;
Lumbar Vertebrae/surgery*
;
Spondylolisthesis/surgery*
;
Scoliosis
;
Spinal Fusion/methods*
9.Treatment of stage Ⅱ-Ⅲ Kümmell disease with robot-assisted bone cement-augmented pedicle screw fixation.
Jian-Qiao ZHANG ; Xiao ZHOU ; Hui-Gen LU ; Bao CHEN ; Ye-Feng YU ; Xu-Qi HU ; Min-Jie HU ; Xue-Kang PAN
China Journal of Orthopaedics and Traumatology 2023;36(5):465-472
OBJECTIVE:
To evaluate the early clinical efficacy of robot-assisted percutaneous short-segment bone cement-augmented pedicle screw fixation in the treatment of stageⅡ-Ⅲ Kümmell disease.
METHODS:
The clinical data of 20 patients with stageⅡ-Ⅲ Kümmell's disease who underwent robot-assisted percutaneous bone cement-augmented pedicle screw fixation between June 2017 and January 2021 were retrospectively analyzed. There were 4 males and 16 females, aged from 60 to 81 years old with an average age of (69.1±8.3) years. There were 9 cases of stageⅡand 11 cases of stage Ⅲ, all of which were single vertebral lesions, including 3 cases of T11, 5 cases of T12, 8 cases of L1, 3 cases of L2, and 1 case of L3. These patients did not exhibit symptoms of spinal cord injury. The operation time, intraoperative blood loss, and complications were recorded. The position of pedicle screws and the filling and leakage of bone cement in gaps were observed using postoperative CT 2D reconstruction. The data of the visual analogue scale (VAS), Oswestry disability index (ODI), kyphosis Cobb angle, wedge angle of the diseased vertebra, and anterior and posterior vertebral height on lateral radiographs were statistically analyzed preoperatively, 1 week postoperatively, and at the final follow-up.
RESULTS:
Twenty patients were followed up for 10 to 26 months, with an average follow-up of (16.0±5.1) months. All operations were successfully completed. The surgical duration ranged from 98 to 160 minutes, with an average of (122±24) minutes. The intraoperative blood loss ranged from 25 to 95 ml, with an average of (45±20) ml. There were no intraoperative vascular nerve injuries. A total of 120 screws were inserted in this group, including 111 screws at grade A and 9 screws at grade B according to the Gertzbein and Robbins scales. Postoperative CT indicated that the bone cement was well-filled in the diseased vertebra, and cement leakage occurred in 4 cases. Preoperative VAS and ODI were (6.05±0.18) points and (71.10±5.37)%, respectively, (2.05±0.14) points and (18.57±2.77)% at 1 week after operation, and (1.35±0.11) points and (15.71±2.12) % at final follow-up. There were significant differences between postoperative 1 week and preoperative, and between final follow-up and postoperative 1 week(P<0.01). Anterior and posterior vertebral height, kyphosis Cobb angle, and wedge angle of the diseased vertebra were(45.07±1.06)%, (82.02±2.11)%, (19.49±0.77) °, and (17.56±0.94) ° preoperatively, respectively, (77.00±0.99)%, (83.04±2.02)%, (7.34±0.56) °, and (6.15±0.52) ° at 1 week postoperatively, and (75.13±0.86)%, (82.39±0.45)%, (8.38±0.63) °, and (7.09±0.59) ° at the final follow-up.
CONCLUSION
Robot-assisted percutaneous short-segment bone cement-augmented pedicle screw fixation demonstrates satisfactory short-term efficacy in treating stageⅡ-Ⅲ Kümmell's disease as an effective minimally invasive alternative. However, longer operation times and strict patient selection criteria are necessary, and long-term follow-up is required to determine its lasting effectiveness.
Male
;
Female
;
Humans
;
Middle Aged
;
Aged
;
Aged, 80 and over
;
Pedicle Screws
;
Bone Cements
;
Robotics
;
Blood Loss, Surgical
;
Retrospective Studies
;
Spinal Fractures/surgery*
;
Lumbar Vertebrae/injuries*
;
Treatment Outcome
;
Kyphosis
;
Thoracic Vertebrae/injuries*
;
Fracture Fixation, Internal
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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