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
;
MicroRNAs/metabolism*
;
Pyroptosis/genetics*
;
Mesenchymal Stem Cells/metabolism*
;
Myocytes, Cardiac/cytology*
;
Mice
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Male
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Mice, Inbred C57BL
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Dental Pulp/cytology*
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Myocardial Reperfusion Injury/therapy*
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MAP Kinase Signaling System/physiology*
2.Outcome Impact of Quantitative Flow Ratio-guided Revascularization in Elderly Patients With Coronary Artery Disease Undergoing Valve Surgery
Fang ZHANG ; Wei GAO ; Wenshuo WANG ; Jinying ZHOU ; Jingpu WANG ; Qiyu ZHANG ; Rende XU ; Chunsheng WANG ; Chenguang LI ; Junbo GE
Chinese Circulation Journal 2025;40(9):878-884
Objectives:This study aimed to investigate the impact of quantitative flow ratio(QFR)-guided revascularization on outcome of elderly patients with coronary artery disease(CAD)undergoing valve surgery.Methods:We retrospectively analyzed 750 consecutive patients with angiographically confirmed CAD(≥50%stenosis)who underwent valve surgery at Zhongshan Hospital,Fudan University,between January 2016 and December 2021.According to the patients'ages,they were divided into the younger group(age<70 years old,n=532)and the elderly group(age≥70 years old,n=218).Revascularization strategies were evaluated using anatomical(angiography-based)and functional(QFR-based)criteria.Anatomical complete revascularization(CR)was defined as bypass grafting for all lesions with≥70%diameter stenosis in major coronary arteries or≥50%stenosis in the left main coronary artery.Functional CR referred bypass grafting for all lesions with QFR≤0.80.Incomplete revascularization(ICR)was defined as failure to meet CR criteria.According to the anatomical and functional definitions,the younger group and the elderly group were further divided into the incomplete revascularization subgroup and the complete revascularization subgroup respectively.Major adverse cardiovascular events(MACE),including death,myocardial infarction,repeat revascularization,and stroke,were assessed as the composite endpoint.Results:Over a follow-up of(3.7±1.8)years,the overall MACE rate was 13.3%.The younger group exhibited significantly lower MACE rates than the elderly group(10.7%vs.19.7%,P=0.001).In the younger group,anatomical ICR did not increase MACE risk(HR=1.46,95%CI:0.81-2.62,P=0.164),whereas functional ICR significantly increased MACE risk(HR=2.27,95%CI:1.24-4.15,P=0.001).In the elderly group,neither anatomical ICR(HR=1.22,95%CI:0.62-2.41,P=0.540)nor functional ICR(HR=1.52,95%CI:0.78-2.96,P=0.172)was associated with increased MACE risk.Conclusions:In patients undergoing valve surgery with CAD,functional ICR correlated with adverse outcomes in the younger group,whereas neither anatomical nor functional ICR significantly affected prognosis in elderly patients.These findings suggest that a moderately conservative revascularization strategy may be more appropriate for elderly populations.
3.Outcome Impact of Quantitative Flow Ratio-guided Revascularization in Elderly Patients With Coronary Artery Disease Undergoing Valve Surgery
Fang ZHANG ; Wei GAO ; Wenshuo WANG ; Jinying ZHOU ; Jingpu WANG ; Qiyu ZHANG ; Rende XU ; Chunsheng WANG ; Chenguang LI ; Junbo GE
Chinese Circulation Journal 2025;40(9):878-884
Objectives:This study aimed to investigate the impact of quantitative flow ratio(QFR)-guided revascularization on outcome of elderly patients with coronary artery disease(CAD)undergoing valve surgery.Methods:We retrospectively analyzed 750 consecutive patients with angiographically confirmed CAD(≥50%stenosis)who underwent valve surgery at Zhongshan Hospital,Fudan University,between January 2016 and December 2021.According to the patients'ages,they were divided into the younger group(age<70 years old,n=532)and the elderly group(age≥70 years old,n=218).Revascularization strategies were evaluated using anatomical(angiography-based)and functional(QFR-based)criteria.Anatomical complete revascularization(CR)was defined as bypass grafting for all lesions with≥70%diameter stenosis in major coronary arteries or≥50%stenosis in the left main coronary artery.Functional CR referred bypass grafting for all lesions with QFR≤0.80.Incomplete revascularization(ICR)was defined as failure to meet CR criteria.According to the anatomical and functional definitions,the younger group and the elderly group were further divided into the incomplete revascularization subgroup and the complete revascularization subgroup respectively.Major adverse cardiovascular events(MACE),including death,myocardial infarction,repeat revascularization,and stroke,were assessed as the composite endpoint.Results:Over a follow-up of(3.7±1.8)years,the overall MACE rate was 13.3%.The younger group exhibited significantly lower MACE rates than the elderly group(10.7%vs.19.7%,P=0.001).In the younger group,anatomical ICR did not increase MACE risk(HR=1.46,95%CI:0.81-2.62,P=0.164),whereas functional ICR significantly increased MACE risk(HR=2.27,95%CI:1.24-4.15,P=0.001).In the elderly group,neither anatomical ICR(HR=1.22,95%CI:0.62-2.41,P=0.540)nor functional ICR(HR=1.52,95%CI:0.78-2.96,P=0.172)was associated with increased MACE risk.Conclusions:In patients undergoing valve surgery with CAD,functional ICR correlated with adverse outcomes in the younger group,whereas neither anatomical nor functional ICR significantly affected prognosis in elderly patients.These findings suggest that a moderately conservative revascularization strategy may be more appropriate for elderly populations.
4.Health risk assessment of eight chemicals in urban drinking water in Inner Mongolia Autonomous Region in 2021
Wenyu ZHANG ; Sheng GAO ; Chenguang ZHANG ; Xinrui JIA ; Huan LI ; Xuanzhi YUE ; Duoduo WU ; Yaochun FAN ; Yuhan QIN
Journal of Environmental and Occupational Medicine 2023;40(11):1283-1289
Background The safety of drinking water is closely related to people's health. In recent years, relevant studies have identified some health related problems with drinking water in Inner Mongolia Autonomous Region. The complex and diverse natural environment embraced by the vast jurisdiction of the region may lead to uneven drinking water quality across the region. Objective To evaluate eight chemicals including arsenic, cadmium, chromium (hexavalent), lead, mercury, fluoride, trichloromethane, and carbon tetrachloride in urban drinking water in Inner Mongolia Autonomous Region in 2021, and to provide reference for optimizing urban water supply system and ideas for further developing strategies to promote population health. Methods A total of 1228 monitoring sites were set up in urban areas of Inner Mongolia, and water samples were collected once in dry season (May) and once in wet season (August−September). Eight chemicals of interest in drinking water were detected according to the Standard examination methods for drinking water, and assessed for health risks using the health risk assessment model recommended by the United States Environmental Protection Agency (USEPA) and following the Technical guide for environmental health risk assessment of chemical exposure. Mann-Whitney U test was used to compare the concentrations of eight chemicals in urban drinking water by water seasons and water sample types. Results In 2021, a total of 2381 samples of urban drinking water were tested in the Inner Mongolia Autonomous Region, including 1195 samples in wet season and 1186 samples in dry season; 389 samples of finished water and 1992 samples of tap water. The positive rates of arsenic and fluoride were 26.25% and 96.77%, respectively. The positive rates of cadmium, chromium (hexavalent), lead, mercury, trichloromethane, and carbon tetrachloride were 6.22%, 16.63%, 6.09%, 16.67%, 18.98%, and 8.36%, respectively. The exceeding standard rate of fluoride was 4.87%. Trichloromethane and carbon tetrachloride were qualified in all samples. There were statistical differences in the concentrations of arsenic, cadmium, chromium (hexavalent), lead, and carbon tetrachloride in urban drinking water between water seasons (Z=−3.847, P<0.05; Z=2.464, P=0.014; Z=−3.129, P=0.002; Z=4.341, P<0.05; Z=4.342, P<0.05). Only fluoride concentration was found statistically different among different water sample types (Z=−2.287, P=0.022). The non-carcinogenic risks of ingestion and dermal exposure to each chemical in drinking water by water seasons and water sample types were all less than 1, but the P95 total non-carcinogenic risks of oral exposure were greater than 1. The P95 carcinogenic risks of oral exposure to some chemicals in drinking water by water seasons and water sample types were>10−4, which suggested carcinogenic risks, while the carcinogenic risks of dermal explore to chemicals were all less than 10−6. Conclusion In 2021, urban drinking water in Inner Mongolia Autonomous Region is generally safe, but arsenic, cadmium, chromium (hexavalent), lead, mercury, and fluoride still exceed the national limits, posing certain health risks.
6.Risk factors for neuropathic pain after a spinal cord injury: A retrospective study
Mulan XU ; Xiaolong SUN ; Xiangbo WU ; Miaoqiao SUN ; Hong WANG ; Yani ZHANG ; Mi GAO ; Xu HU ; Hui CAO ; Wei SUN ; Chenguang ZHAO ; Hua YUAN
Chinese Journal of Physical Medicine and Rehabilitation 2022;44(3):199-203
Objective:To examine the risk factors for neuropathic pain (NP) after a spinal cord injury (SCI).Methods:A total of 115 patients with a SCI were analyzed retrospectively. They were divided into an NP group of 53 and a non-NP group of 62 according to the occurrence of NP. Gender, age, length of stay, occupation, level of education, cause of injury, spinal fracture, degree of SCI, the injury′s plane and complications at admission (diabetes, hypertension, anemia, venous thrombosis, pressure sores, urinary tract infection or hypoproteinemia) were recorded. T-tests and chi-squared tests were used to compare those factors between the two groups, and multivariate logistic regressions were evaluated to identify the risk factors for NP.Results:Twenty-three of the 53 cases of NP (43%) had developed within 1 month of the SCI. Thirty-seven (75%) experienced pain below the plane of the SCI. The main features reported were squeezing (34%) and numbness (26%). The multivariate logistic regression showed that the occurrence of NP was most strongly related to gender (women being particularly at risk) and venous thrombosis at admission.Conclusions:Women are at particular risk of feeling NP after an SCI, and venous thrombosis is an independent risk factor. NP should be diagnosed and treated quickly to reduce the negative impact on patients′ life quality.
7. Tangshen formula improves cholesterol uptake and efflux of macrophages induced by high lipid via activating PGC-1α/LXR/ABCA1 pathway
Ke XU ; Junwei GAO ; Chenguang WU ; Feng TIAN ; Lifan WANG ; Peng LIU ; Zhengri SHEN ; Hui JIA ; Ping LI
Chinese Journal of Clinical Pharmacology and Therapeutics 2021;26(9):978-985
AIM: To observe the effects of Tangshen formula (TSF) treatment on lipid efflux and uptake in sodium palmitate (PA) induced RAW264.7 macrophages. METHODS: After 200 μmol/L PA induced RAW264.7 macrophages, TSF and PGC-1α-siRNA were given to intervene respectively. The lipid content in the cells was detected by ELISA kit; intracellular lipid droplet deposition was detected by BODIPY 493/503 and Filipin staining. Western blot and Real-time PCR were used to detect the expression of PGC-1α, LXR, ABCA1 and CD36. RESULTS: TSF diminished the levels of TC, TG and intracellular lipid droplet deposition in PA-induced RAW264.7 macrophages. Western blot and Real-time PCR analysis showed that TSF could up-regulate the expression of PGC-1α, LXR, ABCA1 and down-regulate the expression of CD36. Furthermore, silencing PCG-1α by SiRNA significantly suppressed the effects of upregulating the expression of PGC-1α, LXR and ABCA1, and downregulating the CD36 expression with TSF treatment. CONCLUSION: TSF may extenuate intracellular lipid droplet deposition in macrophages by upregulating cholesterol efflux through activating the PGC-1α/LXR/ABCA1 pathway and inhibiting lipid uptake through down-regulateing the expression of CD36.
8.MRI Diagnosis of Fetal Intracranial Hemorrhage
Lixia ZHOU ; Chenguang KOU ; Jingying BO ; Duo GAO ; Caiying LI ; Zuojun GENG
Chinese Journal of Medical Imaging 2018;26(4):252-257
Purpose To investigate the diagnostic value of prenatal MRI in fetal intracranial hemorrhage (FICH). Materials and Methods The imaging and clinical data of 41 cases of FICH accepting MRI diagnosis were retrospectively analyzed. The hemorrhage location, signal characteristics and the associated intracranial abnormalities were observed. The pregnancy outcomes and clinical data after birth were followed up. The correlation between periventricular hemorrhage/intraventricular hemorrhage (PVH/IVH) classification and clinical outcomes was analyzed by combining prenatal risk factors. Results Forty-one cases of FICH were evaluated. There were 23 cases of multifocal cerebral hemorrhage and 18 cases of single focal hemorrhage. According to the bleeding site, the 41 cases were classified into PVH/IVH (33 cases), cerebral hemispheres near cortex hemorrhage (3 cases), cerebellar hemorrhage (2 cases), subdural hemorrhage (2 cases) and subarachnoid hemorrhage (1 case). Most of the FICH cases were in subacute period (36/41) and a few were in chronic period or forming encephalomalacia (5/41). The associated changes included ventriculomegaly, vascular malformation, agenesis of corpus callosum, agenesis of vermis, etc. Follow-up results showed that there were 25 cases of labor induction (autopsy after labor induction was performed in 3 cases), 16 cases were followed-up after birth. Among the 16 newborn, there was 1 case of PVH/IVH grade II fetus showing left ear hearing loss after birth, 1 case of grade II fetus showed dyskinesia within one year after birth, and 1 case of grade IV fetus showed unilateral limb movement disorder. The other 13 cases had no obvious neurological sequelae. Spearman correlation test of ranked data indicated that PVH/IVH classification was moderately correlated with birth outcome (r=0.689, P<0.05). Conclusion Prenatal MRI can evaluate the type and severity of fetal intracranial hemorrhage, and provide references for clinical diagnosis and treatment.
9.Podophyllotoxin derivative LN-13 induced multidrug resistant cell K562/A02 apoptosis and its molecular mechanism
Chenguang GAO ; Cai ZHANG ; Anni ZHAO ; Nan LI ; Hong CHEN ; Bo CAO
Chinese Pharmacological Bulletin 2017;33(1):100-104
Aim To study the mechanism of action of the new derivative of podophyllotoxin(LN-13)in indu-cing the apoptosis of K562/A02 cells.Methods The MTT method was taken to detect the inhibition of LN-13 and VP-16 on K562/A02 proliferation and inhibi-tion rate and IC50 values were obtained 48 hours later. The K562/A02 cell morphological change induced by LN-13 were observed through Hochest33342 and PI staining after 48 hours later.Flow cytometry was taken to detect the apoptosis of K562/A02 cells induced by LN-13.The reverse transcription-polymerase chain re-action was taken to detect the Bcl-2,Bax,caspase-3 and mdr-1 mRNA expression.The expression of P-gp was detected by Western blot.Results The growth of K562 /A02 cells was obviously inhibited by LN-13 when IC50 value was 3.32 μmol · L-1 .LN-13 could obviously induced cell apoptosis observed by Ho-chest33342 and PI staining.Flow cytometry detection showed that LN-13(2,4,8 μmol·L-1 )could induce cell apoptosis and apoptosis ratio reached 15.0%, 48.0%,68.96%,respectively.The reverse transcrip-tion-polymerase chain reaction showed that LN-13 in-creased the Bax and Caspase-3 mRNA expression,and meanwhile the expression of mdr-1 mRNA decreased. Western blot showed that P-gp expression was de-creased as the LN-13 dose increased.The data were significantly different from those of control group.Con-clusion Podophyllotoxin derivative LN-13 can induce the apoptosis of K562 /A02 cells,which may be close-ly-related to regulating P-gp expression and apoptosis related gene mRNA expression.
10.Advances in the research of hemodynamics of the pathogenesis of intracranial aneurysms
Dan ZHANG ; Caiying LI ; Bulang GAO ; Fangying JIA ; Chenguang KOU ; Cen WANG
Journal of Interventional Radiology 2017;26(4):378-382
Hemodynamics is a discipline that studies the effects of blood flow,blood flow volume and other factors on the arterial wall.Intracranial aneurysm is the main cause of death due to non-traumatic subarachnoid hemonhage,which has brought a heavy burden on society.Therefore,it is very important to make an intensive study of the pathogenesis of aneurysm.With the development of medical imaging technology and fluid mechanics software in recent years,it becomes possible to make the precise and scientific studies of the hemodynamics of intracranial aneurysms.In this paper,the hemodynamic factors inducing the formation of intracranial aneurysm that are proposed by medical experts at home and abroad are reviewed,and the hemodynamic mechanism is discussed.

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