1.Human umbilical cord mesenchymal stem cell-derived exosomes attenuate renal ischemia-reperfusion injury by up-regulating ATF3 to inhibit the TLR4/NF-κB pathway
Xingyu* WAN ; Yujia LIU ; Ruiyan WANG ; Hao WANG ; Yi ZHAO ; Lu GUO ; Zhihua YANG ; Xinghua LÜ
Organ Transplantation 2026;17(2):275-286
Objective To investigate the protective effect and underlying mechanism of human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Exo) on renal ischemia-reperfusion injury (IRI). Methods hucMSC-Exos were isolated and characterized. A mouse renal IRI model was established and the animals were divided into Sham, IRI, IRI+hucMSC-Exo, IRI+hucMSC-Exo+JY-2 and Sham+JY-2 groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) were measured. Hematoxylin-eosin (HE) staining was used to evaluate renal histopathology. Enzyme-linked immune absorbent assay was performed to determine serum interleukin (IL)-1β and IL-18 levels. Western blotting was used to detect the expression of activating transcription factor 3 (ATF3), Toll-like receptor 4 (TLR4), nuclear factor (NF)-κB, NOD-like receptor protein 3 (NLRP3), cysteineyl aspartate specific proteinase (Caspase)-1 p20 and Gasdermin D(GSDMD). Real-time fluorescent quantitative polymerase chain reaction was employed to measure ATF3, TLR4 and NF-κB messenger RNA (mRNA). Immunohistochemistry was conducted to examine NLRP3, Caspase-1 p20 and GSDMD. An in vitro hypoxia/reoxygenation (H/R) model was established in HK-2 cells and divided into Control, H/R, H/R+hucMSC-Exo, H/R+hucMSC-Exo+JY-2 and Control+JY-2 groups. Western blotting was used to detect the expression of ATF3, TLR4 and NF-κB. Real-time fluorescent quantitative polymerase chain reaction was used to measure NLRP3, GSDMD and Caspase-1 mRNA. Results HucMSC-Exos were successfully isolated and identified. Compared with the Sham group, the IRI group exhibited elevated Scr and BUN, higher tubular injury scores, increased protein expression levels of ATF3, TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD, and raised mRNA expression levels of ATF3, TLR4, NF-κB. Compared with the IRI group, the IRI+hucMSC-Exo group showed decreased Scr and BUN, lower tubular injury scores, up-regulated ATF3 protein and mRNA, down-regulated TLR4, NF-κB p65, NLRP3, Caspase-1 p20 and GSDMD protein, and declined TLR4 and NF-κB mRNA. Compared with the IRI+hucMSC-Exo group, the IRI+hucMSC-Exo+JY-2 group exhibited increased Scr and BUN levels, elevated renal tubular injury scores, decreased ATF3 protein expression levels, elevated protein expression levels of TLR4, NF-κB p65, NLRP3, Caspase-1 p20, and GSDMD, decreased ATF3 mRNA expression levels, and elevated mRNA expression levels of TLR4 and NF-κB. (all P < 0.05). Compared with the Control group, the expression levels of ATF3, TLR4 and NF-κB p65 proteins were increased in the H/R group, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased. Compared with the H/R group, the expression level of ATF3 protein was increased, the expression levels of TLR4 and NF-κB p65 proteins were decreased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were decreased in the H/R+hucMSC-Exo group. Compared with the H/R+hucMSC-Exo group, the expression level of ATF3 protein was decreased, the expression levels of TLR4 and NF-κB p65 proteins were increased, and the expression levels of NLRP3, Caspase-1 and GSDMD mRNA were increased in the H/R+hucMSC-Exo+JY-2 group (all P < 0.05). Conclusions HucMSC-Exos alleviate renal IRI by up-regulating ATF3, thereby negatively regulating the TLR4/NF-κB signaling pathway and subsequently inhibiting pyroptosis.
2.Consensus on informed consent for orthodontic treatment
Yang CAO ; Bing FANG ; Zuolin JIN ; Hong HE ; Yuxing BAI ; Lin WANG ; Haiping LU ; Zhihe ZHAO ; Tianmin XU ; Weiran LI ; Min HU ; Jinlin SONG ; Jun WANG ; Fang JIN ; Ding BAI ; Xianglong HAN ; Yuehua LIU ; Bin YAN ; Jie GUO ; Jiejun SHI ; Yongming LI ; Zhihua LI ; Xiuping WU ; Jiangtian HU ; Linyu XU ; Lin LIU ; Yi LIU ; Yanqin LU ; Wensheng MA ; Shuixue MO ; Liling REN ; Shuxia CUI ; Yongjie FAN ; Jianguang XU ; Lulu XU ; Zhijun ZHENG ; Peijun WANG ; Rui ZOU ; Chufeng LIU ; Lunguo XIA ; Li HU ; Weicai WANG ; Liping WU ; Xiaoxing KOU ; Jiali TAN ; Yuanbo LIU ; Bowen MENG ; Yuantao HAO ; Lili CHEN
Chinese Journal of Stomatology 2025;60(12):1327-1336
This consensus was developed by the Orthodontic Society of the Chinese Stomatological Association to provide a systematic, scientific, and practical guideline for informed consent in orthodontic care. Orthodontic treatment is typically lengthy, highly individualized, and involves multiple factors such as growth and development, occlusal function, and facial esthetics. Rapid technological advances and diverse risk profiles make the traditional reliance on orthodontist experience or institutional templates insufficient to ensure patients′ full understanding and autonomous decision-making. To address this, the expert panel conducted extensive reviews of domestic and international guidelines, analyzed representative dispute cases, and performed multicenter patient-clinician surveys. Using a multi-round Delphi method, the group established a standardized informed consent framework covering the initial consultation, treatment, and retention phases. The consensus emphasizes that informed consent is not only a fundamental legal and ethical requirement but also a key step in building trust, improving patient compliance, and enhancing treatment satisfaction. Orthodontists should clearly and comprehensively explain treatment plans, potential risks, uncertainties, and associated costs, while respecting the autonomy of patients or guardians, and maintain continuous communication and dynamic evaluation throughout the treatment process. The release of this consensus provides unified and authoritative guidance for clinical orthodontics, helping to standardize informed consent, enhance its transparency, safeguard patient rights, reduce medical risks, and promote high-quality, sustainable development of orthodontic practice.
3.Digital design and manufacturing method of double constrained split guide for orthodontic miniscrew implantation.
Xin DU ; Aonan WEN ; Zixiang GAO ; Zhihua LI ; Sheng ZHANG ; Yong WANG ; Yijiao ZHAO
West China Journal of Stomatology 2025;43(4):603-612
This study explored a novel digital design and fabrication method for a double constrained split orthodontic miniscrew guide to improve the accuracy and safety of clinical miniscrew implantation and reduce related complications. A patient requiring miniscrew implantation was selected, and data were acquired using cone beam computed tomography (CBCT) and intraoral optical scanning. For the construction of a double constrained split guide including a screw-hole guide and an insertion rod guide, different types of software such as Mimics 24.0, Geomagic wrap 2021, and Materialise magics 21.0 were utilized for 3D reconstruction, model integration, and guide design. The guide was then fabricated via laser metal 3D printing. Model and intraoral try-in results demonstrated that the guide fitted well and was stable. Postoperative CBCT verified that the final miniscrew implantation site was consistent with the preoperative design, and no related complications occurred. This double constrained split orthodontic miniscrew guide provides a precise and safe digital solution for clinical miniscrew implantation.
Humans
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Bone Screws
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Cone-Beam Computed Tomography
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Printing, Three-Dimensional
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Orthodontic Anchorage Procedures/instrumentation*
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Imaging, Three-Dimensional
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Computer-Aided Design
4.Surgical techniques and clinical outcomes of upper urinary tract reconstruction for stone-related ureteral strictures
Xiaoteng YU ; Yixuan HUANG ; Xinfei LI ; Changfu CHEN ; Fangzhou ZHAO ; Honggang YING ; Zihao TAO ; Yiming ZHANG ; Liqing XU ; Zhihua LI ; Kunlin YANG ; Liqun ZHOU ; Xuesong LI ; Zheng ZHAO
Journal of Peking University(Health Sciences) 2025;57(4):670-675
Objective:To summarize the surgical strategies and to evaluate the clinical outcomes of up-per urinary tract reconstruction in patients with stone-related ureteral strictures.Methods:This retro-spective study included 71 patients diagnosed with ureteral strictures secondary to urinary stones who un-derwent upper urinary tract reconstructive surgery at Peking University First Hospital between March 2014 and November 2023.Patient data were collected,including demographic characteristics,clinical presen-tation,laboratory results,imaging findings,surgical procedures,and follow-up outcomes.Ureteral stric-tures were classified according to anatomical location into upper,middle,lower,or multiple segments.Surgical procedures were carried out depending on the stricture characteristics.Surgical success was de-fined as resolution or improvement of clinical symptoms,radiographic improvement or stabilization of hy-dronephrosis,and maintenance of normal and stable renal function.Results:Among the 71 patients,36(50.7%)had strictures in the upper ureter,9(12.7%)in the middle ureter,15(21.1%)in the lower ureter,and 11(15.5%)had multifocal ureteral strictures.The median stricture length was 5.0 cm(interquartile range:3.0-15.0 cm).Surgical approach selection was individualized based on the location and extent of the stricture.For upper ureteral strictures,the most frequently employed techniques were oral mucosal graft ureteroplasty(13/36,36.1%)and appendiceal flap ureteroplasty(8/36,22.2%).Other options included ureteroureterostomy and ileal ureter replacement for longer or more complex strictures.In middle ureteral strictures,treatment was stratified by length:balloon dilation(1/9,11.1%)and ureteroureterostomy(1/9,11.1%)were applied in shorter strictures,while oral mucosal graft ureteroplasty(3/9,33.3%)and ileal ureter replacement(4/9,44.4%)were reserved for longer segments.For lower ureteral strictures,ureteral reimplantation into the bladder was the most common approach(10/15,66.7%),often combined with a psoas hitch or Boari flap when necessary.All the patients with multiple segmental strictures underwent ileal ureter replacement due to the extensive nature of the disease.The median follow-up period was 14.2 months(range:6.1-107.1 months).During follow-up,69 of 71 patients(97.2%)achieved surgical success.Conclusion:Stone-related ure-teral strictures present with considerable heterogeneity in terms of anatomical location,length,and com-plexity.Careful preoperative evaluation and individualized surgical planning are critical to successful re-construction.With appropriate selection of surgical methods,favorable long-term clinical outcomes can be achieved in the majority of patients.
5.Construction and in vitro performance testing of a multi-modified hemerythrin-based nano-oxygen carrier
Zhihua HUANG ; Huimin ZHAO ; Chunyuan SU ; Kang YANG
Chinese Journal of Tissue Engineering Research 2025;29(22):4740-4747
BACKGROUND:Molecular stability and biocompatibility of hemerythrin surpass those of human and mammalian hemoglobin,making it a potential candidate for a safer and more effective erythrocyte substitute after modification.OBJECTIVE:To prepare multi-modified hemerythrin nanoparticles,characterize them,and test their performance in vitro.METHODS:The hemerythrin of Sipunculus sphenodontus was separated and purified by tangential flow ultrafiltration.The intramolecular cross-linking was completed by genipin.The nanoparticles were encapsulated by dopamine,and passivated by polyethylene glycol to obtain multi-modified hemerythrin nanoparticles.The physicochemical properties of the nanoparticles were characterized.Hemerythrin nanoparticles,hemerythrin,and hemoglobin oxygen carrier HBOC-201 with different mass concentrations(0,0.25,0.5,1.0,and 2.0 mg/mL)were incubated with macrophages for 6 and 24 hours,and with endothelial cells for 24 hours.The cell survival rate was detected by CCK-8 assay.The levels of nitric oxide and vascular cell adhesion factor 1 in the culture medium of endothelial cells were detected by ELISA.RESULTS AND CONCLUSION:(1)Under electron microscopy,hemerythrin nanoparticles were ellipsoidal,with a dense outer membrane and a relatively uniform internal texture.The particle size was(150.12±1.67)nm;the dispersion index was 0.21±0.03;the Zeta potential was(-24.54±2.61)mV;the half-saturated oxygen partial pressure was(0.97±0.15)kPa,and the Hill coefficient was 1.49±0.16.(2)After incubation for 6 hours,within the mass concentration range of≤1.0 mg/mL,the survival rates of macrophages in the hemerythrin nanoparticle group,the hemerythrin group,and the HBOC-201 group were all above 85%.At a mass concentration of 2.0 mg/mL,only the survival rate of macrophages in the hemerythrin nanoparticle group was above 80%.After incubation for 24 hours,the survival rates of macrophages in the three groups were all lower than 80%,among which the survival rate of macrophages in the hemerythrin nanoparticle group was higher than that in the hemerythrin group and the HBOC-201 group(P<0.05).(3)With the increase of drug concentration,the survival rate of vascular endothelial cells in the three groups decreased.At 1.0 mg/mL or 2.0 mg/mL mass concentration,the survival rate of cells in the hemerythrin nanoparticle group was higher than that in the hemerythrin group and HBOC-201 group(P<0.05).At the same mass concentration,the nitric oxide level in the hemerythrin nanoparticle group was higher than that in the hemerythrin group and HBOC-201 group(P<0.05).In the range of 0.25-2.0 mg/mL mass concentration,the vascular cell adhesion factor 1 level in the hemerythrin nanoparticle group was lower than that in the hemerythrin group and HBOC-201 group(P<0.05).(4)The results showed that the hemerythrin nanoparticles modified with intramolecular cross-linking and polydopamine/polyethylene glycol had good oxygen-carrying activity in vitro,better anti-phagocytic performance,and less cytotoxicity.
6.Clinical efficacy of minimally invasive coronary artery bypass grafting via left intercostal small incision for multivessel coronary artery disease: A retrospective cohort study
Zeyuan ZHAO ; Zhihua WANG ; Sheng WANG ; Xianjie CHEN ; Zhao LI ; Guoqing LU ; Zhenchang QI ; Zhaoyun CHENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(10):1455-1461
Objective To investigate the early clinical efficacy of minimally invasive cardiac surgery coronary artery bypass grafting (MICS CABG) via left intercostal small incision for multivessel coronary artery disease. Methods The patients who received off-pump CABG in the Central China Fuwai Hospital of Zhengzhou University from June 2021 to June 2023 were enrolled. Patients were divided into two groups according to the operative technique used, including a traditional midline sternotomy group and a left intercostal small incision group. The clinical data of the two groups were compared. Results A total of 143 patients were enrolled, including 70 patients in the traditional midline sternotomy group and 73 patients in the left intercostal small incision group. The age of the patients in the left intercostal small incision group and the traditional midline sternotomy group was (63.8±8.0) years and (63.0±7.8) years, respectively; the proportions of males were 69.9% and 74.3%, respectively. The differences were not statistically significant (all P>0.05). All patients in the two groups successfully completed the operation, and no patients in the left intercostal small incision group were converted to thoracotomy. The patients in the left intercostal small incision group showed less postoperative drainage within postoperative 24 hours [(239.4±177.7) mL vs. (338.0±151.9) mL, P<0.001], lower perioperative blood transfusion rate [32.9% (24/73) vs. 51.4% (36/70), P=0.028], higher postoperative myoglobin level within postoperative 24 hours [366.1 (247.9, 513.0) ng/mL vs. 220.8 (147.2, 314.9) ng/mL, P<0.001], shorter intensive care unit stay [45.5 (31.5, 67.5) h vs. 68.0 (46.0, 78.5) h, P=0.001] and postoperative hospital stay [(10.8±4.0) d vs. (13.1±5.3) d, P=0.028] compared to the traditional midline sternotomy group. There was no significant difference in the incidence of major adverse cardiac and cerebrovascular event between the two groups [2.7% (2/73) vs. 2.9% (2/70), P=1.000]. Conclusion Compared to the full median sternotomy, MICS CABG leads to a good clinical result with smaller trauma, faster overall recovery, and less perioperative blood transfusion.
7.Complete transcatheter versus surgical aortic valve replacement for aortic valve stenosis with coronary artery disease: A propensity score matching study
Zhihua WANG ; Zeyuan ZHAO ; Junlong HU ; Yaojue SONG ; Chenyi CUI ; Jiahui LI ; Jianchao LI ; Zhaoyun CHENG
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(12):1708-1715
Objective To compare and analyze the early- to mid-term outcomes of transcatheter aortic valve replacement (TAVR) combined with percutaneous coronary intervention (PCI) versus surgical aortic valve replacement (SAVR) combined with coronary artery bypass grafting (CABG) for the treatment of significant aortic stenosis (AS) and coronary artery disease (CAD). Methods The data of patients with significant AS and CAD who underwent surgical treatment at Central China Fuwai Hospital of Zhengzhou University from January 2018 to July 2023 were collected. These patients were divided into a TAVR+PCI group and a SAVR+CABG group according to the operation method. Propensity score matching (PSM) was used to select patients with close clinical baseline characteristics, and the early- to mid-term outcomes of the two groups were compared. Results A total of 272 patients were enrolled, including 208 males and 64 females, with a mean age of (64.16±8.24) years. There were 47 patients in the TAVR+PCI group and 225 patients in the SAVR+CABG group. After 1 : 1 PSM, 32 pairs were selected. There was no statistical difference in baseline data between the two groups (P>0.05). Compared with the SAVR+CABG group, the TAVR+PCI group had significantly shorter operative time, mechanical ventilation time, ICU stay, postoperative hospital stay, and less intraoperative bleeding, and significantly lower postoperative transfusion and complete revascularization rates (P<0.05). The differences in the rates of postoperative in-hospital death, myocardial infarction, stroke, or other complications between the two groups were not statistically significant (P>0.05), and the differences in the rates of moderate-to-severe perivalvular leakage, death, or readmission in the mid-term follow-up were not statistically significant (P>0.05). Conclusion In patients with significant AS and CAD, the early- and mid-term rates of death and complications are similar between those treated with TAVR+PCI and SAVR+CABG, and TAVR+PCI is a safe alternative to SAVR+CABG.
8.The relationship between SII,RDW and 25(OH)D levels and frailty index in elderly patients with type 2 diabetes mellitus
Zhihua ZHOU ; Qian WANG ; Nan YANG ; Xiaoying WANG ; Hong GONG ; Meng GUO ; Jieqiong ZHAO
International Journal of Laboratory Medicine 2025;46(13):1626-1630
Objective To explore the relationship between systemic immune-inflammation index(SII),red blood cell distribution width(RDW),25-hydroxy-vitamin-D[25(OH)D]levels and frailty index in elderly pa-tients with type 2 diabetes mellitus(T2DM).Methods A total of 197 elderly patients with T2DM admitted to the hospital from March 2023 to March 2024 were collected as the research subjects.The patients were divided into the frailty group(106 cases)and the non-frailty group(91 cases)according to the scores of the clinical frailty scale.The clinical data and the levels of SII,RDW and 25(OH)D of the two groups were compared.Pearson correlation analysis was used to analyze the correlations between the levels of SII,RDW and 25(OH)D and the frailty index of elderly patients with T2DM.Logistic regression was used to analyze the influencing factors of frailty in elderly patients with T2DM.Results Compared with the non-frailty group,the proportion of women,the history of falls within 1 year,and the age of the frailty group increased,while the body mass in-dex and the proportion of men decreased,and the differences were statistically significant(P<0.05).The SII and RDW levels in the non-frailty group were lower than those in the frailty group,and the 25(OH)D level was higher than that in the frailty group,and the differences were statistically significant(P<0.05).Pearson correlation analysis showed that SII and RDW levels were positively correlated with frailty index,and 25(OH)D level was negatively correlated with frailty index in elderly T2DM patients(P<0.05).Logistic regression analysis showed that female,age ≥ 74.25 years old,SII≥ 938.36,RDW≥ 15.19%,and 25(OH)D≥48.42 nmol/L were independent risk factors for frailty in elderly T2DM patients(P<0.05).Conclusion The levels of SII,RDW and 25(OH)D in elderly patients with T2DM are related to the frailty index.
9.Research progress on postoperative quality of life in adult patients with ureteropelvic junction obstruction
Zhihua LI ; Man ZHANG ; Xiang WANG ; Han ZHAO ; Qiang ZHANG ; Xinfei LI ; Kunlin YANG ; Xuesong LI
International Journal of Surgery 2025;52(10):657-661
Ureteropelvic junction obstruction, as a common urological disorder, not only affects the renal function of patients, but also seriously reduces their quality of life. Pyeloplasty, as the first-line therapy for ureteral stricture at present, is a key approach to eliminating hydronephrosis and improving renal function. The quality of life of postoperative patients, as an important criterion for measuring the therapeutic effect, has also attracted increasing attention. Therefore, this article reviews the evaluation tools, research status and influencing factors of the postoperative quality of life of ureteropelvic junction obstruction patients, aiming to provide a reference for the formulation of relevant nursing intervention measures in clinical practice.
10.Role of RhoE gene expression changes in myocardial fibrosis in diabetic cardiomyopathy
Kaijia SHI ; Xinglin ZHU ; Yangyang ZHAO ; Jinxuan CHAI ; Zhihua SHEN ; Junli GUO ; Wei JIE
Chinese Journal of Cardiology 2025;53(3):293-300
Objective:To explore the role and mechanism of Ras homolog gene family member E (RhoE) gene in myocardial fibrosis in diabetic cardiomyopathy.Methods:Wild-type SD rats were intraperitoneally injected with streptozotocin solution (STZ, 70 mg/kg) and an equal volume of sodium citrate solution to establish the type 1 diabetes mellitus (T1DM) group ( n=15) and the T1DM control group ( n=15), respectively. db/db spontaneous type 2 diabetes mellitus (T2DM) mice and wild-type C57BL/6J mice were conventionally housed for 8 weeks to establish the T2DM group ( n=5) and the T2DM control group ( n=5), respectively. Heterozygote SD rats with systemic knockout of the RhoE gene were intraperitoneally injected with STZ solution (70 mg/kg) and an equal volume of sodium citrate solution to establish the RhoE knockout T1DM group ( n=5) and the RhoE knockout control group ( n=5), respectively. Wild-type SD rats were injected with RhoE-overexpressing adeno-associated virus 9 through tail vein and intraperitoneally injected with STZ solution (70 mg/kg) to establish the RhoE overexpression T1DM group ( n=5), while wild-type SD rats injected with negative control virus through tail vein and intraperitoneally injected with an equal volume of sodium citrate solution served as the RhoE overexpression control group ( n=5). After successful modeling, all animals in each group were conventionally housed for an additional 6 or 8 weeks, which marked the experimental endpoint. At the experimental endpoint, echocardiography was performed to assess cardiac function of animals in each group, and left ventricular ejection fraction (LVEF) and the ratio of early to late diastolic transmitral flow velocity (E/A ratio) were analysed. Masson staining was used to detect collagen fiber deposition in myocardial tissue of animals in each group. Western blot analysis was conducted to detect the expression levels of RhoE gene, type Ⅰ collagen, type Ⅲ collagen, Smad2/3, and phosphorylated Smad2/3 protein in myocardial tissue of rats. Enzyme-linked immunosorbent assay was used to measure the levels of transforming growth factor-β1 (TGF-β1) in serum of rats. Results:Compared with their respective control groups, the expression of RhoE in the heart tissues of mice in the T2DM group and rats in the T1DM group was significantly downregulated, and the deposition of collagen fibers was more significant ( P<0.05), and LVEF and E/A ratio were lower (all P<0.05). Compared with the T1DM group, the phosphorylation level of Smad2/3、the levels of type Ⅰ collagen and type Ⅲ collagen in myocardial tissue and the level of TGF-β1 in serum were higher in the RhoE knockout T1DM group (all P<0.05). Additionally, rats in the RhoE overexpression T1DM group had higher LVEF and E/A ratios (both P<0.05) and less collagen fiber deposition ( P<0.05) compared with the T1DM group. Conclusions:Myocardial fibrosis induced by diabetes mellitus activates TGF-β1/Smads signaling pathway by inhibiting RhoE gene expression. Myocardial targeting overexpression of the RhoE mediated by adeno-associated virus 9 can alleviate myocardial fibrosis and improve cardiac function in rats with diabetic cardiomyopathy.

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