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Mitochondrial transplantation confers protection against the effects of ischemic stroke by repressing microglial pyroptosis and promoting neurogenesis

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Neural Regeneration Research 2024年第6期19卷 1325-1335页

作者： Li Sun Zhaoyan Zhao Jing Guo Yuan Qin Qian Yu Xiaolong Shi Fei Guo Haiqin Zhang Xude Sun Changjun Gao Qian Yang department of Experimental Surgery The Second Affiliated Hospital of Air Force Medical University department of Anesthesiology The Second Affiliated Hospital of Air Force Medical University

Transferring healthy and functional mitochondria to the lateral ventricles confers neuroprotection in a rat model of ischemia-reperfusion injury. Autologous mitochondrial transplantation is also beneficial in pediatric patients with cardiac ischemia-reperfusion injury. Thus, transplantation of functional exogenous mitochondria may be a promising therapeutic approach for ischemic disease. To explore the neuroprotective effect of mitochondria transplantation and determine the underlying mechanism in ischemic stroke, in this study we established a photo-thrombosis-induced mouse model of focal ischemia and administered freshly isolated mitochondria via the tail vein or to the injury site(in situ). Animal behavior tests, immunofluorescence staining, 2,3,5-triphenyltetrazolium chloride(TTC) staining, mRNA-seq, and western blotting were used to assess mouse anxiety and memory, cortical infarct area, pyroptosis, and neurogenesis, respectively. Using bioinformatics analysis, western blotting, co-immunoprecipitation, and mass spectroscopy, we identified S100 calcium binding protein A9(S100A9) as a potential regulator of mitochondrial function and determined its possible interacting proteins. Interactions between exogenous and endogenous mitochondria, as well as the effect of exogenous mitochondria on recipient microglia, were assessed in vitro. Our data showed that:(1) mitochondrial transplantation markedly reduced mortality and improved emotional and cognitive function, as well as reducing infarct area, inhibiting pyroptosis, and promoting cortical neurogenesis;(2) microglial expression of S100A9 was markedly increased by ischemic injury and regulated mitochondrial function;(3) in vitro, exogenous mitochondria enhanced mitochondrial function, reduced redox stress, and regulated microglial polarization and pyroptosis by fusing with endogenous mitochondria; and(4) S100A9 promoted internalization of exogenous mitochondria by the microglia, thereby amplifying their pro-prolifera

关键词： ischemic stroke microglia mitochondria transplantation neurogenesis pyroptosis

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Dapagliflozin in heart failure and type 2 diabetes:Efficacy,cardiac and renal effects,safety

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World Journal of Diabetes 2024年第7期15卷 1518-1530页

作者： Pei-Ling Yu You Yu Shuang Li Bai-Chen Mu Ming-Hua Nan Min Pang The second department of cardiology The Second Affiliated Hospital of Liaoning Hospital of Traditional Chinese MedicineShenyang 110034Liaoning ProvinceChina department of Outpatient The Second Affiliated Hospital of Liaoning University of Traditional Chinese MedicineShenyang 110034Liaoning ProvinceChina

BACKGROUND Heart failure(HF),especially HF with reduced ejection fraction(HFrEF),presents complex challenges,particularly in the aging population where it often coexists with type 2 diabetes mellitus(T2DM).AIM To analyze the effect of dapagliflozin treatment on cardiac,renal function,and safety in patients with HFrEF combined with *** Patients with T2DM complicated with HFrEF who underwent treatment in our hospital from February 2018 to March 2023 were retrospectively analyzed as the subjects of this *** propensity score matching method was used,and a total of 102 eligible samples were *** clinical efficacy of the two groups was evaluated at the end of the treatment,comparing the results of blood glucose,insulin,cardiac function,markers of myocardial injury,renal function indexes,and 6-min walk test(6MWT)before and after the *** compared the occurrence of adverse effects on the treatment process of the two groups of *** incidence of adverse outcomes in patients within six months of treatment was *** The overall clinical efficacy rate of patients in the study group was significantly higher than that of patients in the control group(P=0.013).After treatment,the pancreatic beta-cell function index,left ventricular ejection fraction,and glomerular filtration rate of patients in the study group were significantly higher than control group(P<0.001),while their fasting plasma glucose,2-h postprandial glucose,glycosylated hemoglobin,insulin resistance index,left ventricular end-systolic diameter,left ventricular end-diastolic diameter,cardiac troponin I,creatine kinase-MB,N-terminal pro b-type natriuretic peptide,serum creatinine,and blood urea nitrogen were significantly lower than those of the control *** treatment,patients in the study group had a significantly higher 6MWT than those in the control group(P<0.001).Hypoglycemic reaction(P=0.647),urinary tract infection(P=0.558),gastrointestinal adverse effect(P=0.

关键词： Heart failure Type 2 diabetes mellitus Heart failure with preserved ejection fraction Myocardial infarction markers Cardiac function

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Serum metabolic profiling implicates mTOR activation and insulin resistance in the development of pulmonary hypertension in a rat model of pressure overload-induced heart failure

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Genes & Diseases 2024年第5期11卷 109-112页

作者： Qi Zhou Chao Tang Xinke Xu Junhao Hu Shengsen Yao Bo Dong Xiaojing Wu department of cardiology of the Fifth affiliated hospital of Southern Medical University GuangzhouGuangdong 510999China Cardiovascular department of Shenzhen University General hospital ShenzhenGuangdong 518055China Cardiovascular department of Chongqing Medical University second affiliated hospital Chongqing 400010China

Pulmonary hypertension(PH)due to left heart failure(HF)accounts for approximately half of PH cases *** has been demonstrated that PH is a frequent complication of HF but is difficult to recognize in its early stage because it is characterized by nonspecific symptoms including shortness of breath and decreased tolerance of ***,nearly all multicentric clinical trials targeting pulmonary circulation in PH-HF have reported negative results.1 Thus,there are no effective methods for diagnosing early PH,and the current treatment of PH-HF is insufficient.

关键词： hypertension Serum resistance

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Hydroxysafflor yellow A induced ferroptosis of Osteosarcoma cancer cells by HIF-1α/HK2 and SLC7A11 pathway

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Oncology Research 2024年第5期32卷 899-910页

作者： YIWEN ZHU LIU YANG YING YU YING XIONG PING XIAO XIAO FU XIN LUO department of Rehabilitation Medicine The Second Affiliated Hospital of Nanchang UniversityNanchang330006China department of General Practice The Second Affiliated Hospital of Nanchang UniversityNanchang330006China

Osteosarcoma is a very serious primary bone cancer with a high death rate and a dismal *** there is no permanent therapy for this condition,it is necessary to develop a ***,this investigation was carried out to assess the impacts and biological functions of hydroxysafflor yellow A(HYSA)in osteosarcoma cell lines(MG63).In this investigational study,MG63 cells were *** experiments,quantitative polymerase chain reaction(qPCR),immunofluorescent staining,extracellular acidification rate(ECAR),oxygen consumption rate(OCR),glucose consumption,lactate production,and ATP levels,proliferation assay,5-Ethynyl-2′-deoxyuridine(EDU)staining,and Western blot were *** MG63 cells,HYSA lowered cell proliferation and metastasis rates,suppressed EDU cell number,and enhanced caspase-3/9 activity *** reduced the Warburg effect and induced ferroptosis(FPT)in MG63 *** ferroptosis diminished HYSA’s anti-cancer activities in MG63 *** stimulation of the HIF-1α/SLC7A11 pathway decreased HYSA’s anti-cancer activities in MG63 ***-1αis one target spot for HYSA in a model of osteosarcoma cancer(OC).HYSA altered HIF-1α’s thermophoretic activity;following binding with HYSA,HIF-1α’s melting point increased from~55°C to~60°*** significantly enhanced the thermal stability of exogenous WT HIF-1αwhile not affecting Mut HIF-1α,suggesting that ARG-311,GLY-312,GLN-347,and GLN-387 may be involved in the interaction between HIF-1αand ***,our study revealed that HYSA induced FPT and reduced the Warburg effect of OC through mitochondrial damage by HIF-1α/HK2/SLC7A11 *** is a possible therapeutic option for OC or other cancers.

关键词： Hydroxysafflor yellow A Osteosarcoma HIF-1α FPT

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Conquer coronary artery perforation with magic hands

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Journal of Geriatric cardiology 2024年第4期21卷 379-386页

作者： Yi-Lun ZOU Jian-Qiang LI Ding-Yu WANG Yong-Tai GONG Li SHENG Yue LI department of cardiology the First Affiliated Hospital of Harbin Medical UniversityHarbinChina

Coronary artery perforation(CAP) poses a significant challenge for interventional cardiologists. Management of CAP depends on the location and severity of the perforation. The conventional method for addressing the perforation of large vessels involves the placement of a covered stent, while the perforation of distal and collateral vessels is typically managed using coils, autologous skin, subcutaneous fat, microspheres, gelatin sponge, thrombin or other substances. However, the above techniques have certain limitations and are not applicable in all scenarios. Our team has developed a range of innovative strategies for effectively managing CAP. This article provides an insightful review of the various tips and tricks for the treatment of CAP.

关键词： coronary sponge perforation

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Effect of negative remodeling of the side branch ostium on the efficacy of a two-stent strategy for distal left main bifurcation lesions:an intravascular ultrasound study

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Journal of Geriatric cardiology 2024年第5期21卷 506-522页

作者： Yi XU Tian XU Jia-Cong NONG Xiao-Han KONG Meng-Yao ZHAO Zhi-Jing GAO Yi-Fei WANG Wei YOU Pei-Na MENG Yu-He ZHOU Xiang-Qi WU Zhi-Ming WU Mei-En ZHAN Yan-Qing WANG De-Feng PAN Fei YE department of cardiology Nanjing First HospitalNanjing Hospital Affiliated to Nanjing Medical UniversityNanjing Medical UniversityNanjingChina department of cardiology Clinical Medicine School of Nanjing UniversityNanjingChina department of cardiology Tianchang People’s HospitalTianchangChina department of cardiology the Affiliated Hospital of Xuzhou Medical UniversityXuzhouChina

OBJECTIVES To investigate whether negative remodeling(NR) detected by intravascular ultrasound(IVUS) of the side branch ostium(SBO) would affect in-stent neointimal hyperplasia(NIH) at the one-year follow-up and the clinical outcome of target lesion failure(TLF) at the long-term follow-up for patients with left main bifurcation(LMb) lesions treated with a two-stent *** A total of 328 patients with de novo true complex LMb lesions who underwent a 2-stent strategy of percutaneous coronary intervention(PCI) treatment guided by IVUS were enrolled in this study. We divided the study into two phases. Of all the patients, 48 patients who had complete IVUS detection pre-and post-PCI and at the 1-year follow-up were enrolled in phase Ⅰ analysis, which aimed to analyze the correlation between NR and in-stent NIH at SBO at the 1-year follow-up. If the correlation was confirmed, the cutoff value of the remodeling index(RI) for predicting NIH ≥ 50% was analyzed next. The phase Ⅱ analysis focused on the incidence of TLF as the primary endpoint at the 1-to 5-year follow-up for all 328 patients by grouping based on the cutoff value of *** In phase I: according to the results of a binary logistic regression analysis and receiver operating characteristic(ROC) analysis, the RI cutoff value predicting percent NIH ≥ 50% was 0.85 based on the ROC curve analysis, with a sensitivity of 85.7%, a specificity of 88.3%, and an AUC of 0.893(0.778, 1.000), P = 0.002. In phase Ⅱ: the TLR rate(35.8% vs. 5.3%, P < 0.0001)was significantly higher in the several NR(s NR, defined as RI ≤ 0.85) group than in the non-s NR *** The NR of LCx O is associated with more in-stent NIH post-PCI for distal LMb lesions with a 2-stent strategy,and NR with RI ≤ 0.85 is linked to percent NIH area ≥ 50% at the 1-year follow-up and more TLF at the 5-year follow-up.

关键词： lesions remodeling intravascular

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Metadherin promotes stem cell phenotypes and correlated with immune infiltration in hepatocellular carcinoma

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World Journal of Gastroenterology 2024年第8期30卷 901-918页

作者： Yi-Ying Wang Mei-Mei Shen Jian Gao department of Gastroenterology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China department of Gastroenterology and Hepatology The Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of *** To explore the role of MTDH on stemness and immune infiltration in *** MTDH expression in HCC tissues was detected using TCGA and GEO *** was used to analyze the tissue *** was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell *** invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing ***,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free *** expression was determined by western blotting and quantitative reverse transcri-ption *** cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like *** effects of MTDH inhibition on tumor growth were evaluated in *** correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB *** HCC tissues expressed higher levels of MTDH than normal liver *** MTDH expression was associated with a poor *** cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these *** inhibition suppressed HCC progression and CD133 expression in *** was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T *** was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 a

关键词： Metadherin Hepatocellular carcinoma Cancer stem cells Immune infiltration

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Cardiac Piezo1 Exacerbates Lethal Ventricular Arrhythmogenesis by Linking Mechanical Stress with Ca^(2+) Handling After Myocardial Infarction

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Research 2024年第1期2023卷 583-594页

作者： Sheng-an Su Yuhao Zhang Wudi Li Yutao Xi Yunrui Lu Jian Shen Yuankun Ma Yaping Wang Yimin Shen Lan Xie Hong Ma Yao Xie Meixiang Xiang department of cardiology Cardiovascular Key Laboratory of Zhejiang ProvinceThe Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China department of Endocrinology The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Texas Heart Institute HoustonTX 77030USA

Ventricular arrhythmogenesis is a key cause of sudden cardiac death following myocardial infarction(MI).Accumulating data show that ischemia,sympathetic activation,and inflammation contribute to ***,the role and mechanisms of abnormal mechanical stress in ventricular arrhythmia following MI remain *** aimed to examine the impact of increased mechanical stress and identify the role of the key sensor Piezo1 in ventricular arrhythmogenesis in *** with increased ventricular pressure,Piezo1,as a newly recognized mechano-sensitive cation channel,was the most up-regulated mechanosensor in the myocardium of patients with advanced heart ***1 was mainly located at the intercalated discs and T-tubules of cardiomyocytes,which are responsible for intracellular calcium homeostasis and intercellular communication.

关键词： ventricular homeostasis Ventricular

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Macroscopic on-site magnifier-based evaluation to estimate visible tissue core cut-off lengths using EUS-FNA with 22-gauge needles

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Chinese Medical Journal 2024年第4期137卷 493-495页

作者： Jialiang Huang Guilian Cheng Wei Wu Liming Xu Longjiang Xu Duanmin Hu department of Gastroenterology Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215004China department of Pathology Second Affiliated Hospital of Soochow UniversitySuzhouJiangsu 215004China

To the Editor:Endoscopic ultrasound-guided fine needle aspiration(EUS-FNA)has replaced other high-risk invasive methods and has become the primary method of tissue collection around the gastrointestinal tract.^([1])To further improve the effectiveness and safety of EUS-FNA,pathologists may perform rapid on-site cytology evaluation(ROSE),but this process requires the presence of *** on-site evaluation(MOSE)has gained attention as it resolve the shortage of pathologist resources.^([2])Endoscopists can inspect the tissue core in real time and assess the adequacy of the punctured *** this study,we conducted a single-center and single-arm exploratory study to explore the value of MOSE in assessing specimen quality during magnifier-based EUS-FNA and to confirm the cut-off length of visible tissue core(VTC)for EUS-FNA to help endosonographers independently predict the adequacy of punctured *** VTC was defined as a white or incarnadine tissue core obtained from focal lesions with a relatively complete histological structure.

关键词： EUS needle visible

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Subclinical impairment of left ventricular myocardium function in type 2 diabetes mellitus patients with or without hypertension

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World Journal of Diabetes 2024年第6期15卷 1272-1279页

作者： Zeng-Guang Chen Guang-An Li Jun Huang Li Fan department of cardiology The Affiliated Changzhou Second People’s Hospital with Nanjing Medical UniversityChangzhou 213000Jiangsu ProvinceChina department of Echocardiography The Affiliated Changzhou Second People’s Hospital with Nanjing Medical UniversityChangzhou 213000Jiangsu ProvinceChina

BACKGROUND Cardiovascular disease has been the leading cause of morbidity and mortality for type 2 diabetes mellitus(T2DM)patients over the last *** To determine whether layer-specific global longitudinal strain(GLS)combined with peak strain dispersion(PSD)can be used to assess left ventricle(LV)myocardium systolic dysfunction in T2DM patients or without hypertension(HP).METHODS We enrolled 97 T2DM patients,70 T2DM+HP patients and 101 healthy ***-specific GLS and PSD were calculated by EchoPAC software in apical three-,four-and two-chamber *** of the epimyocardial,middle-layer and endomyocardial(GLSepi,GLSmid,and GLSendo)were measured and *** operating characteristic analysis was performed to detect LV myocardium systolic dysfunction in T2DM *** There were significant differences in GLSepi,GLSmid,GLSendo,and PSD between healthy subjects,T2DM patients and T2DM patients with HP(PT2DM patients>T2DM with HP patients in the absolute values of GLSepi,GLSmid and GLSendo(P<0.001),while PSD was ranked healthy subjects

关键词： Type 2 diabetes mellitus Hypertension Speckle tracking echocardiography Global longitudinal strain Peak strain dispersion

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