1.Cardiomyocyte pyroptosis inhibited by dental pulp-derived mesenchymal stem cells via the miR-19a-3p/IRF-8/MAPK pathway in ischemia-reperfusion.
Yi LI ; Xiang WANG ; Sixian WENG ; Chenxi XIA ; Xuyang MENG ; Chenguang YANG ; Ying GUO ; Zuowei PEI ; Haiyang GAO ; Fang WANG
Chinese Medical Journal 2025;138(18):2336-2346
BACKGROUND:
The protective effect of mesenchymal stem cells (MSCs) on cardiac ischemia-reperfusion (I/R) injury has been widely reported. Dental pulp-derived mesenchymal stem cells (DP-MSCs) have therapeutic effects on various diseases, including diabetes and cirrhosis. This study aimed to determine the therapeutic effects of DP-MSCs on I/R injury and elucidate the underlying mechanism.
METHODS:
Myocardial I/R injury model mice were treated with DP-MSCs or a miR-19a-3p mimic. The infarct volume, fibrotic area, pyroptosis, inflammation level, and cardiac function were measured. Cardiomyocytes exposed to hypoxia-reoxygenation were transfected with the miR-19a-3p mimic, miR-19a-3p inhibitor, or negative control. Pyroptosis and protein expression in the interferon regulatory factor 8/mitogen-activated protein kinase (IRF-8/MAPK) pathway were measured.
RESULTS:
DP-MSCs protected cardiac function in cardiac I/R-injured mice and inhibited cardiomyocyte pyroptosis. The upregulation of miR-19a-3p protected cardiac function, inhibited cardiomyocyte pyroptosis, and inhibited IRF-8/MAPK signaling in cardiac I/R-injured mice. DP-MSCs inhibited cardiomyocyte pyroptosis and the IRF-8/MAPK signaling by upregulating the miR-19a-3p levels in cardiomyocytes injured by I/R.
CONCLUSION
DP-MSCs protected cardiac function by inhibiting cardiomyocyte pyroptosis through miR-19a-3p under I/R conditions.
Animals
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MicroRNAs/metabolism*
;
Pyroptosis/genetics*
;
Mesenchymal Stem Cells/metabolism*
;
Myocytes, Cardiac/cytology*
;
Mice
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Male
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Mice, Inbred C57BL
;
Dental Pulp/cytology*
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Myocardial Reperfusion Injury/therapy*
;
MAP Kinase Signaling System/physiology*
2.Analysis of the clinical efficacy of percutaneous transluminal angioplasty in treating dysfunction of autogenous arteriovenous fistula
Jingcun SU ; Haiyang WANG ; Junbo LI ; Huawen XIA
Journal of Practical Radiology 2025;41(4):656-659
Objective To investigate the efficacy of percutaneous transluminal angioplasty(PTA)in the treatment of dysfunction of autogenous arteriovenous fistula(AVF),and to analyze the factors influencing 12-month patency.Methods The data from maintenance hemodialysis patients who underwent PTA for AVF stenosis were collected.The technical success rate,clinical success rate,complications,and short-to medium-term AVF patency were evaluated.Univariate analysis and binary logistic regression were used to identify predictors of 12-month post-procedural patency.Results A total of 70 patients were included in this study.The technical and clinical success rates were 94.29%and 95.71%,respectively.The 3-,6-,and 12-month post-procedural patency rates of AVF were 97.1%,75.7%,and 61.4%,respectively.Independent protective factors for 12-month AVF patency included age<60 years[odds ratio(OR)=0.277,95%confidence interval(CI)0.097-0.792]and statin use(OR=0.299,95%CI 0.101-0.887).Independent risk factors included diabetes mellitus(OR=5.167,95%CI 1.824-14.64),AVF usage≥1 year(OR=2.885,95%CI 1.061-7.840),and non-use of aspirin(OR=2.782,95%CI 1.016-7.615).Conclusion PTA is a safe and effective treatment for AVF stenosis,though long-term patency rates require further improvement.
3.Early PCSK9 Inhibitor Therapy Following Percutaneous Coronary Intervention (PERFECT): A Pilot Randomized Controlled Trial
Jiachun XIA ; Zhengguang XIAO ; Luyao WU ; Haiyang YU ; Yanan PANG ; Shan HU ; Lei HOU
Cardiology Discovery 2025;05(1):62-68
Objective::This study aimed to assess the impact of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor treatment immediately after percutaneous coronary intervention (PCI) on the myocardial salvage index (MSI) in patients with anterior ST-segment elevation myocardial infarction (STEMI) 5-10 d after the procedure.Methods::The early PCSK9 inhibitor thERapy Following pErcutaneous Coronary inTervention (PERFECT) trial is a prospective randomized controlled trial. From January 2021 to December 2023, 32 patients with anterior STEMI from Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and Shanghai Tenth People’s Hospital were enrolled in the PERFECT trial. Patients were randomly assigned in a 1∶1 ratio to the PCSK9 inhibitor group ( n = 16) or the control group ( n = 16), and their baseline data were collected. Patients in the PCSK9 inhibitor group (ie, alirocumab group) received a subcutaneous injection of PCSK9 inhibitor (alirocumab, 75 mg) immediately after PCI based on conventional treatment. In the control group, patients received only conventional treatment. The primary endpoint was the MSI measured by cardiovascular magnetic resonance 5-10 d after PCI. The secondary endpoints included the left ventricular ejection fraction measured by cardiovascular magnetic resonance 5-10 d after PCI and the time to peak of creatine kinase isoenzyme-MB and high-sensitivity cardiac troponin T. Safety endpoints included any clinical adverse events that occurred during the 6-month follow-up period. Results::Baseline data during admission showed no intergroup significance. No significant difference in MSI (55.54% ± 14.80% vs. 44.72% ± 15.42%, P = 0.056) and left ventricular ejection fraction (51.24% ± 8.91% vs. 44.99% ± 8.84%, P = 0.060) was observed. Additional, there was no significant difference in the time to peak of creatine kinase isoenzyme-MB ((12.97 ± 5.67) h vs. (14.31 ± 7.04) h, P = 0.557) and high-sensitivity cardiac troponin T ((21.03 ± 12.46) h vs. (21.44 ± 9.99) h, P = 0.920) between the 2 groups. During the 6-month follow-up period, only 1 patient in the PCSK9 inhibitor group developed cerebral hemorrhage 6 months after PCI. Conclusions::Early treatment with alirocumab did not exhibit a significant increase in MSI at 5-10 d in patients with anterior STEMI. Larger trials are necessary to evaluate the impact of early administration of PCSK9 inhibitors after myocardial infarction.
4.Early PCSK9 Inhibitor Therapy Following Percutaneous Coronary Intervention (PERFECT): A Pilot Randomized Controlled Trial
Jiachun XIA ; Zhengguang XIAO ; Luyao WU ; Haiyang YU ; Yanan PANG ; Shan HU ; Lei HOU
Cardiology Discovery 2025;05(1):62-68
Objective::This study aimed to assess the impact of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor treatment immediately after percutaneous coronary intervention (PCI) on the myocardial salvage index (MSI) in patients with anterior ST-segment elevation myocardial infarction (STEMI) 5-10 d after the procedure.Methods::The early PCSK9 inhibitor thERapy Following pErcutaneous Coronary inTervention (PERFECT) trial is a prospective randomized controlled trial. From January 2021 to December 2023, 32 patients with anterior STEMI from Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and Shanghai Tenth People’s Hospital were enrolled in the PERFECT trial. Patients were randomly assigned in a 1∶1 ratio to the PCSK9 inhibitor group ( n = 16) or the control group ( n = 16), and their baseline data were collected. Patients in the PCSK9 inhibitor group (ie, alirocumab group) received a subcutaneous injection of PCSK9 inhibitor (alirocumab, 75 mg) immediately after PCI based on conventional treatment. In the control group, patients received only conventional treatment. The primary endpoint was the MSI measured by cardiovascular magnetic resonance 5-10 d after PCI. The secondary endpoints included the left ventricular ejection fraction measured by cardiovascular magnetic resonance 5-10 d after PCI and the time to peak of creatine kinase isoenzyme-MB and high-sensitivity cardiac troponin T. Safety endpoints included any clinical adverse events that occurred during the 6-month follow-up period. Results::Baseline data during admission showed no intergroup significance. No significant difference in MSI (55.54% ± 14.80% vs. 44.72% ± 15.42%, P = 0.056) and left ventricular ejection fraction (51.24% ± 8.91% vs. 44.99% ± 8.84%, P = 0.060) was observed. Additional, there was no significant difference in the time to peak of creatine kinase isoenzyme-MB ((12.97 ± 5.67) h vs. (14.31 ± 7.04) h, P = 0.557) and high-sensitivity cardiac troponin T ((21.03 ± 12.46) h vs. (21.44 ± 9.99) h, P = 0.920) between the 2 groups. During the 6-month follow-up period, only 1 patient in the PCSK9 inhibitor group developed cerebral hemorrhage 6 months after PCI. Conclusions::Early treatment with alirocumab did not exhibit a significant increase in MSI at 5-10 d in patients with anterior STEMI. Larger trials are necessary to evaluate the impact of early administration of PCSK9 inhibitors after myocardial infarction.
5.Analysis of the clinical efficacy of percutaneous transluminal angioplasty in treating dysfunction of autogenous arteriovenous fistula
Jingcun SU ; Haiyang WANG ; Junbo LI ; Huawen XIA
Journal of Practical Radiology 2025;41(4):656-659
Objective To investigate the efficacy of percutaneous transluminal angioplasty(PTA)in the treatment of dysfunction of autogenous arteriovenous fistula(AVF),and to analyze the factors influencing 12-month patency.Methods The data from maintenance hemodialysis patients who underwent PTA for AVF stenosis were collected.The technical success rate,clinical success rate,complications,and short-to medium-term AVF patency were evaluated.Univariate analysis and binary logistic regression were used to identify predictors of 12-month post-procedural patency.Results A total of 70 patients were included in this study.The technical and clinical success rates were 94.29%and 95.71%,respectively.The 3-,6-,and 12-month post-procedural patency rates of AVF were 97.1%,75.7%,and 61.4%,respectively.Independent protective factors for 12-month AVF patency included age<60 years[odds ratio(OR)=0.277,95%confidence interval(CI)0.097-0.792]and statin use(OR=0.299,95%CI 0.101-0.887).Independent risk factors included diabetes mellitus(OR=5.167,95%CI 1.824-14.64),AVF usage≥1 year(OR=2.885,95%CI 1.061-7.840),and non-use of aspirin(OR=2.782,95%CI 1.016-7.615).Conclusion PTA is a safe and effective treatment for AVF stenosis,though long-term patency rates require further improvement.
6.Single-dose AAV-based vaccine induces a high level of neutralizing antibodies against SARS-CoV-2 in rhesus macaques.
Dali TONG ; Mei ZHANG ; Yunru YANG ; Han XIA ; Haiyang TONG ; Huajun ZHANG ; Weihong ZENG ; Muziying LIU ; Yan WU ; Huan MA ; Xue HU ; Weiyong LIU ; Yuan CAI ; Yanfeng YAO ; Yichuan YAO ; Kunpeng LIU ; Shifang SHAN ; Yajuan LI ; Ge GAO ; Weiwei GUO ; Yun PENG ; Shaohong CHEN ; Juhong RAO ; Jiaxuan ZHAO ; Juan MIN ; Qingjun ZHU ; Yanmin ZHENG ; Lianxin LIU ; Chao SHAN ; Kai ZHONG ; Zilong QIU ; Tengchuan JIN ; Sandra CHIU ; Zhiming YUAN ; Tian XUE
Protein & Cell 2023;14(1):69-73
7.Analysis on clinical characteristics of tenofovir disoproxil fumarate-related Fanconi syndrome in patients with HIV infection/AIDS
Hengli LIU ; Xia LI ; Xinping YANG ; Cuixian YANG ; Mi ZHANG ; Huiqin LI ; Shuangmei ZHANG ; Xingqian WU ; Yuwei LI ; Haiyang WANG
Adverse Drug Reactions Journal 2023;25(1):21-27
Objective:To explore the clinical characteristics of tenofovir disoproxil fumarate (TDF)-related Fanconi syndrome (FS) in patients with HIV infection/AIDS (HIV/AIDS).Methods:The medical records of patients with HIV/AIDS who were hospitalized in Yunnan Provincial Hospital of Infectious Diseases from December 2017 to February 2021, treated with antiretroviral therapy (ART) containing TDF, and diagnosed as FS were collected by searching hospital information system. Information such as gender, age, body weight, body mass index (BMI), ART treatment regimen and period, time of FS diagnosis, main clinical characteristics, results of laboratory test at admission and discharge, dual energy X-ray bone mineral density (BMD) test results, and interventions and outcomes were retrospectively analyzed.Results:A total of 16 HIV/AIDS patients were diagnosed with TDF-related FS in the setting period, including 6 patients with complete FS and 10 with incomplete FS. FS were accompanied with chronic hepatitis C, hypertension, liver cancer, or depression in 7 patients. Sixteen patients received ART containing TDF for a minimum of 20 months and a maximum of 168 months with an average time of 68 months. The initial symptoms of FS were bone pain, fatigue, nausea, anorexia, polydipsia, polyuria, weight loss, etc. The time from initial symptoms to diagnosis of FS was 2 weeks at least, 24 weeks at most, with an average time of 7 weeks. Laboratory test results were as follows: all 16 patients had positive urine glucose under normoglycemic conditions and 14 patients had positive urine protein; 11, 11, 4, and 4 patients had low urine phosphorus, hypocalciuria, hypokalemia, and hyponatruria, respectively; 13, 12, 8, and 7 patients had hypophosphatemia, hypokalemia, hypocalcemia, and hyponatremia, respectively; 11 patients had serum creatinine increase; 10 patients had serum uric acid decrease; 1 patient had serum uric acid increase. Dual energy X-ray BMD detection was performed in 15 patients, of which 2, 2, and 11 patients had normal, reduced, and osteoporotic BMD, respectively. After diagnosis of TDF-related FS, 16 patients stopped using TDF immediately. After replacement of ART protocol without TDF and symptomatic treatment for an average time of 29 days, the above symptoms were alleviated, and some laboratory test indicators returned to the reference value range. The prognosis was good.Conclusions:TDF-related FS mostly occurs within 68 months of drug use. The clinical symptoms of FS are nonspecific. Laboratory tests show that urine glucose is positive under normal blood glucose. Most of the patients have low blood phosphorus, low urine phosphorus, hypocalciuria, and osteoporosis. The prognosis is better after discontinuing TDF, replacing therapy with ART regimen without TDF, and giving symptomatic treatments.
8.Analysis on clinical characteristics of tenofovir disoproxil fumarate-related Fanconi syndrome in patients with HIV infection/AIDS
Hengli LIU ; Xia LI ; Xinping YANG ; Cuixian YANG ; Mi ZHANG ; Huiqin LI ; Shuangmei ZHANG ; Xingqian WU ; Yuwei LI ; Haiyang WANG
Adverse Drug Reactions Journal 2023;25(1):21-27
Objective:To explore the clinical characteristics of tenofovir disoproxil fumarate (TDF)-related Fanconi syndrome (FS) in patients with HIV infection/AIDS (HIV/AIDS).Methods:The medical records of patients with HIV/AIDS who were hospitalized in Yunnan Provincial Hospital of Infectious Diseases from December 2017 to February 2021, treated with antiretroviral therapy (ART) containing TDF, and diagnosed as FS were collected by searching hospital information system. Information such as gender, age, body weight, body mass index (BMI), ART treatment regimen and period, time of FS diagnosis, main clinical characteristics, results of laboratory test at admission and discharge, dual energy X-ray bone mineral density (BMD) test results, and interventions and outcomes were retrospectively analyzed.Results:A total of 16 HIV/AIDS patients were diagnosed with TDF-related FS in the setting period, including 6 patients with complete FS and 10 with incomplete FS. FS were accompanied with chronic hepatitis C, hypertension, liver cancer, or depression in 7 patients. Sixteen patients received ART containing TDF for a minimum of 20 months and a maximum of 168 months with an average time of 68 months. The initial symptoms of FS were bone pain, fatigue, nausea, anorexia, polydipsia, polyuria, weight loss, etc. The time from initial symptoms to diagnosis of FS was 2 weeks at least, 24 weeks at most, with an average time of 7 weeks. Laboratory test results were as follows: all 16 patients had positive urine glucose under normoglycemic conditions and 14 patients had positive urine protein; 11, 11, 4, and 4 patients had low urine phosphorus, hypocalciuria, hypokalemia, and hyponatruria, respectively; 13, 12, 8, and 7 patients had hypophosphatemia, hypokalemia, hypocalcemia, and hyponatremia, respectively; 11 patients had serum creatinine increase; 10 patients had serum uric acid decrease; 1 patient had serum uric acid increase. Dual energy X-ray BMD detection was performed in 15 patients, of which 2, 2, and 11 patients had normal, reduced, and osteoporotic BMD, respectively. After diagnosis of TDF-related FS, 16 patients stopped using TDF immediately. After replacement of ART protocol without TDF and symptomatic treatment for an average time of 29 days, the above symptoms were alleviated, and some laboratory test indicators returned to the reference value range. The prognosis was good.Conclusions:TDF-related FS mostly occurs within 68 months of drug use. The clinical symptoms of FS are nonspecific. Laboratory tests show that urine glucose is positive under normal blood glucose. Most of the patients have low blood phosphorus, low urine phosphorus, hypocalciuria, and osteoporosis. The prognosis is better after discontinuing TDF, replacing therapy with ART regimen without TDF, and giving symptomatic treatments.
9.Analysis of clinical effect and complication prevention and treatment of autogenous arteriovenous fistulas stenosis by intravenous intervention therapy
Jingcun SU ; Huawen XIA ; Haiyang WANG ; Junbo LI ; Aihong SHEN
Clinical Medicine of China 2020;36(5):431-434
Objective:To explore the clinical effect and safety of interventional treatment of autogenous arteriovenous fistula(AVF) stenosis.Methods:From July 2017 to September 2018, 96 patients with arteriovenous fistula stenosis and occlusion admitted to Handan First Hospital, Hebei Province were retrospectively analyzed.All of them were dialysis patients with chronic renal failure.All patients underwent percutaneous balloon angioplasty via the cephalic vein.The success rate of technique, clinical success rate, perioperative complications and follow-up were observed.Results:(1) Technical success rate and clinical success rate: 90 patients were treated with percutaneous transluminal angioplasty (PTA) via the cephalic vein, the other 3 patients were treated with interventional therapy via the brachial artery, and 3 patients underwent reconstruction of internal fistula.The technical success rate was 93.8% (90/96), and the clinical success rate was 89.6% (86/96). (2) Perioperative complications: thrombosis in 4 cases, vasospasm in 3 cases.There were no serious complications such as vascular rupture, aneurysm, vascular dissection, and no perioperative death.(3) The first stage patency rate was 100% (90/90), 74.4% (67/90), 62.2% (56/90) and 46.7% (42/90) in 3, 6, 12 and 18 months after operation.Conclusion:Venipuncture can be used as the first choice for AVF stenosis interventional therapy because of its advantages of small trauma, no serious complications, no need of long-term compression at the puncture point, immediate dialysis, and avoidance of local hematoma and other complications caused by artery puncture.
10.Analysis of clinical effect of interventional treatment of arteriovenous fistula stenosis through arteriovenous approach
Jingcun SU ; Huawen XIA ; Aihong SHEN ; Haiyang WANG ; Junbo LI
Clinical Medicine of China 2020;36(6):524-528
Objective:To compare the clinical effect and perioperative complications of the treatment of autogenous arteriovenous fistula stenosis by arterial and venous approach.Methods:The clinical data of 120 patients with AVF stenosis and occlusion who were treated with interventional therapy and met the inclusion criteria were collected and analyzed by retrospective case-control study.from September 2017 to August 2018, 60 patients with internal fistula stenosis were treated by transarterial approach (arterial approach group), and from September 2018 to may 2019, 60 patients were treated with a new surgical scheme(venous approach group). The operation success rate, perioperative complications and patency rate of 3, 6, 12 months after operation were compared between the two groups.Results:(1) The technical success rate was 96.7% (58/60) and the clinical success rate was 91.7% (55/60) in the arterial approach group, and 95.0%(57/60) and 93.3%(56/60) in the venous approach group.There was no significant difference in the technical success rate and clinical success rate between the two groups ( P=0.718 and 1.000, respectively) (2) Perioperative complications: in the arterial approach group, 3 patients had hematoma at the puncture point, 2 pseudoaneurysms and 5 thrombosis.There were 3 patients with thrombosis in the venous access group, and the difference in the incidence of complications between the two groups was statistically significant (χ 2=4.227, P=0.036). (3)The primary patency rates at 3, 6 and 12 months after operation were 95.0%(57/60), 75.0%(45/60) and 60.0%(36/60) in the arterial approach group, and 96.7%(58/60), 71.7%(43/60) and 61.7%(37/60) in the venous access group, respectively.There was no statistically significant difference between the two groups ( P=0.718, 0.749, 0.885). Conclusion:The interventional treatment for autogenous arteriovenous fistula stenosis through artery and vein approach can achieve good effect.There were many complications during the perioperative period, It is suggested that venous approach is preferred.

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