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Piezo1 channel exaggerates ferroptosis of nucleus pulposus cells by mediating mechanical stress-induced iron influx

Bone Research 2024年第2期12卷 334-348页

作者： Ziqian Xiang Pengfei Zhang Chunwang Jia Rongkun Xu Dingren Cao Zhaoning Xu Tingting Lu Jingwei Liu Xiaoxiong Wang Cheng Qiu Wenyang Fu Weiwei Li Lei Cheng Qiang Yang Shiqing Feng Lianlei Wang Yunpeng Zhao Xinyu Liu Department of Orthopaedics Qilu Hospital of Shandong UniversityJinan 250012China university of Health and Rehabilitation Sciences Qingdao 226000China Xiangya School of Medicine Central South UniversityChangsha 410013China School of Nursing and Rehabilitation Shandong UniversityJinan 250012China Department of Pediatrics Cangzhou Central HospitalCangzhou 061011China Department of Pediatric Surgery Qilu Hospital of Shandong UniversityJinan 250012China Department of Pathology Qilu Hospital of Shandong UniversityJinan 250012China Department of Spine Surgery Tianjin HospitalTianjin UniversityTianjin 30021China The Second hospital of shandong university Cheeloo College of MedicineShandong UniversityJinan 250012China

To date,several molecules have been found to facilitate iron influx,while the types of iron influx channels remain to be ***,Piezo1 channel was identified as a key iron transporter in response to mechanical ***1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells(NPCs).Importantly,Piezo1-induced iron influx was independent of the transferrin receptor(TFRC),a well-recognized iron ***,pharmacological inactivation of Piezo1 profoundly reduced iron accumulation,alleviated mitochondrial ROS,and suppressed ferroptotic alterations in stimulation of mechanical ***,conditional knockout of Piezo1(Col2a1-CreERT Piezo1^(flox/flox))attenuated the mechanical injury-induced intervertebral disc degeneration(IVDD).Notably,the protective effect of Piezo1 deficiency in IVDD was dampened in Piezo1/Gpx4 conditional double knockout(cDKO)mice(Col2a1-CreERT Piezo1^(flox/flox)/Gpx4^(flox/flox)).These findings suggest that Piezo1 is a potential determinant of iron influx,indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.

关键词： stress overload channel

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Association between Gene Polymorphisms and SNP-SNP Interactions of the Matrix Metalloproteinase 2 Signaling Pathway and the Risk of Vascular Senescence

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Biomedical and Environmental Sciences 2024年第2期37卷 146-156页

作者： LIAO Zhen Yu YANG Shuo HU Song LIU Jia MAO Yong Jun SUN Shu Qin Department of Geriatrics the Affiliated Hospital of Qingdao UniversityQingdao 266000ShandongChina Department of Critical Care Medicine the Affiliated Hospital of Qingdao UniversityQingdao 266000ShandongChina

Objective This study aimed to explore the association of single nucleotide polymorphisms(SNP)in the matrix metalloproteinase 2(MMP-2)signaling pathway and the risk of vascular senescence(VS).Methods In this cross-sectional study,between May and November 2022,peripheral venous blood of151 VS patients(case group)and 233 volunteers(control group)were *** SNPs were identified in five genes encoding the components of the MMP-2 signaling pathway,assessed through carotid-femoral pulse wave velocity(cf PWV),and analyzed using multivariate logistic *** multigene influence on the risk of VS was assessed using multifactor dimensionality reduction(MDR)and generalized multifactor dimensionality regression(GMDR)*** Within the multivariate logistic regression models,four SNPs were screened to have significant associations with VS:chemokine(C-C motif)ligand 2(CCL2)rs4586,MMP2 rs14070,MMP2rs7201,and MMP2 *** of the T/C genotype of MMP2 rs14070 had a 2.17-fold increased risk of developing VS compared with those of the C/C genotype,and those of the T/T genotype had a19.375-fold increased ***2 rs4586 and MMP-2 rs14070 exhibited the most significant *** CCL2 rs4586,MMP-2 rs14070,MMP-2 rs7201,and MMP-2 rs1053605 polymorphisms were significantly associated with the risk of VS.

关键词： Vascular senescence Pulse wave velocity(PWV) Single nucleotide polymorphism(SNP) Matrix metalloproteinase 2(MMP-2) Extracellular matrix(ECM) Structural degradation Multifactor dimensionality reduction(MDR)

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Macrophage exosomes modified by miR-365-2-5p promoted osteoblast osteogenic differentiation by targeting OLFML1

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Regenerative Biomaterials 2024年第3期3卷 134-147页

作者： Caiyao Hou Yujue Zhang Zhaoyong Lv Yurun Luan Jun Li Chunxiu Meng Kun Liu Xin Luo Liyu Chen Fengzhen Liu Department of Materials Science and Engineering Liaocheng UniversityLiaocheng 252000China Liaocheng People's hospital Liaocheng Hospital Affliated Shandong First Medical UniversityLiaocheng 252000China The Second hospital Cheeloo College of MedicineShandong UniversityJinan 250023China

In the bone immune microenvironment,immune cells can regulate osteoblasts through a complex communication *** play a central role in mediating immune osteogenesis,exosomes derived from them have osteogenic regulation and can be used as cariers in bone tissue ***,there are problems with exosomal therapy alone,such as poor targeting,and the content of loaded molecules cannot reach the therapeutic *** this study,macrophage-derived exosomes modified with miR-365-2-5p were developed to accelerate bone ***3T3-E1 cells were incubated with the culture supermatants of Mo,M1 and M2 macrophages,and it was found that the culture medium of M2 macrophages had the most significant effects in contributing to ***-throughput sequencing identified that miR-365-2-5p was significantly expressed in exosomes derived from M2 *** incubated MC3T3-E1 with exosomes overexpressing or kmocking down miR-365-2-5p to examine the biological function of exosome miR-365-2-5p on MC3T3-E1 *** findings suggested that miR-365-2-5p secreted by exosomes increased the osteogenesis of ***,miR-365-2-5p had a direct influence over osteogenesis for *** analysis combined with dual luciferase detection indicated that miR-365-2-5p binded to the 3'-UTR of *** summary,exosomes secreted by M2 macrophages targeted OLFML1 through miR-365-2-5p to facilitate osteogenesis.

关键词： macrophage exosomes osteogenesis osteoimmunology

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Atherosis-associated lnc_000048 activates PKR to enhance STAT1-mediated polarization of THP-1 macrophages to M1 phenotype

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Neural Regeneration Research 2024年第11期19卷 2488-2498页

作者： Yuanyuan Ding Yu Sun Hongyan Wang Hongqin Zhao Ruihua Yin Meng Zhang Xudong Pan Xiaoyan Zhu Department of Neurology The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina Qingdao Cadre Health Care Service Center The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina Department of Critical Care Medicine The Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina

Our previous study has demonstrated that lnc_000048 is upregulated in large-artery atherosclerotic stroke and promotes atherosclerosis in ApoE^(-/-)***,little is known about the role of lnc_000048 in classically activated macrophage(M1)*** this study,we established THP-1-derived testing state macrophages(M0),M1 macrophages,and alternately activated macrophages(M2).Real-time fluorescence quantitative PCR was used to verify the expression of marker genes and the expression of lnc_000048 in *** cytometry was used to detect phenotypic proteins(CD11b,CD38,CD80).We generated cell lines with lentivirus-mediated upregulation or downregulation of lnc_*** cytometry,western blot,and real-time fluorescence quantitative PCR results showed that down-regulation of lnc_000048 reduced M1 macrophage polarization and the inflammation response,while over-expression of lnc_000048 led to the opposite *** blot results indicated that lnc_000048 enhanced the activation of the STAT1 pathway and mediated the M1 macrophage ***,catRAPID prediction,RNA-pull down,and mass spectrometry were used to identify and screen the protein kinase RNA-activated(PKR),then catRAPID and RPIseq were used to predict the binding ability of lnc_000048 to ***(IF)-RNA fluorescence in situ hybridization(FISH)double labeling was performed to verify the subcellular colocalization of lnc_000048 and PKR in the cytoplasm of M1 *** speculate that lnc_000048 may form stem-loop structure-specific binding and activate PKR by inducing its phosphorylation,leading to activation of STAT1 phosphorylation and thereby enhancing STAT1 pathway-mediated polarization of THP-1 macrophages to M1 and inflammatory factor *** together,these results reveal that the lnc_000048/PKR/STAT1 axis plays a crucial role in the polarization of M1 macrophages and may be a novel therapeutic target for atherosclerosis alleviation in stroke.

关键词： atherosclerosis inflammation lnc_000048 lncRNA macrophage polarization protein kinase RNA-activated(PKR) STAT1

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Knee osteoarthritis:A review of animal models and intervention of traditional Chinese medicine

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Animal Models and Experimental Medicine 2024年第2期7卷 114-126页

作者： Xuyu Song Ying Liu Siyi Chen Lei Zhang Huijie Zhang Xianhui Shen Hang Du Rong Sun Orthopaedic trauma surgery The Second Hospital of Shandong UniversityJinanShandongChina Academy of Traditional Chinese Medicine Tianjin University of Traditional Chinese MedicineTianjinChina Department of Traditional Chinese Medicine The Second Hospital of Shandong UniversityJinanShandongChina College of pharmacy Shandong University of Traditional Chinese MedicineJinanShandongChina The Second Clinical College of shandong university Shandong UniversityJinanShandongChina Advanced Medical Research Institute Shandong UniversityJinanShandongChina The Second hospital of shandong university JinanShandongChina

Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging *** pathophysiology of KOA remains poorly understood,as it involves complex mechanisms that result in the same ***,researchers are interested in studying KOA and require appropriate animal models for basic *** herbal compounds,which consist of multiple herbs with diverse pharmacological properties,possess characteristics such as multicomponent,multipathway,and multitarget *** potential benefits in the treatment of KOA continue to attract ***:This study aims to provide a comprehensive overview of the advantages,limitations,and specific considerations in selecting different species and methods for KOA animal *** will help researchers make informed decisions when choosing an animal ***:Online academic databases(e.g.,PubMed,Google Scholar,Web of Science,and CNKI)were searched using the search terms“knee osteoarthritis,”“animal models,”“traditional Chinese medicine,”and their combinations,primarily including KOA studies published from 2010 to ***:Based on literature retrieval,this review provides a comprehensive overview of the methods of establishing KOA animal models;introduces the current status of advantages and disadvantages of various animal models,including mice,rats,rabbits,dogs,and sheep/goats;and presents the current status of methods used to establish KOA animal ***:This study provides a review of the animal models used in recent KOA research,discusses the common modeling methods,and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.

关键词： animal models knee osteoarthritis system review traditional Chinese medicine

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Effects of high-dose glucose-insulin-potassium on acute coronary syndrome patients receiving reperfusion therapy:a meta-analysis

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World Journal of Emergency Medicine 2024年第3期15卷 181-189页

作者： Zeyu Yang Huiruo Liu Dazhou Lu Shengchuan Cao Feng Xu Chuanbao Li Department of Emergency Medicine Qilu Hospital of Shandong UniversityJinan 250012China shandong Provincial Clinical Research Center for Emergency and Critical Care Medicine Institute of Emergency and Critical Care Medicine of Shandong UniversityChest Pain CenterQilu Hospital of Shandong UniversityJinan 250012China Key Laboratory of Emergency and Critical Care Medicine of shandong Province Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong ProvinceShandong Provincial Engineering Laboratory for Emergency and Critical Care MedicineQilu Hospital of Shandong UniversityJinan 250012China shandong Key Laboratory:Magnetic Field-free Medicine&Functional Imaging(MF) Qilu Hospital of Shandong UniversityJinan 250012China National Medical Products Administration(NMPA)Key Laboratory for Clinical Research and Evaluation of Innovative Drug Qilu Hospital of Shandong UniversityJinan 250012China

BACKGROUND:This meta-analysis aimed to assess the efficacy of high-dose glucose-insulinpotassium(GIK) therapy on clinical outcomes in acute coronary syndrome(ACS) patients receiving reperfusion ***:We searched the PubMed,Web of Science,MEDLINE,Embase,and Cochrane Library databases from inception to April 26,2022,for randomized controlled trials(RCTs) that compared high-dose GIK and placebos in ACS patients receiving reperfusion *** primary endpoint was major adverse cardiovascular events(MACEs).RESULTS:Eleven RCTs with 884 patients were ultimately *** with placebos,high-dose GIK markedly reduced MACEs(risk ratio [RR] 0.57,95% confidence interval [95% CI]:0.35 to 0.94,P=0.03) and the risk of heart failure(RR 0.48,95% CI:0.25 to 0.95,P=0.04) and improved the left ventricular ejection fraction(LVEF)(mean difference [MD] 2.12,95% CI:0.40 to 3.92,P=0.02) at 6 ***,no difference was observed in all-cause mortality at 30 d or 1 ***,high-dose GIK was significantly associated with increased incidences of phlebitis(RR 4.78,95% CI:1.36 to 16.76,P=0.01),hyperglycemia(RR 9.06,95% CI:1.74 to 47.29,P=0.009) and hypoglycemia(RR 6.50,95% CI:1.28 to 33.01,P=0.02) but not reinfarction,hyperkalemia or secondary *** terms of oxidative stress-lowering function,high-dose GIK markedly reduced superoxide dismutase(SOD) activity but not glutathione peroxidase(GSH-Px) or catalase(CAT) ***:Patients with ACS receiving reperfusion therapy exhibited a reduction in MACEs and good oxidative stress-lowering eflcacy in response to high-dose ***,with a higher incidence of complications such as phlebitis,hyperglycemia,and ***,there were no observed survival benefits associated with high-dose *** trials with long-term follow-up are still needed.

关键词： Acute coronary syndrome High-dose Glucose-insulin-potassium treatment Reperfusion therapy Meta-analysis

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Efficacy and safety of carrimycin in ten patients with severe pneumonia following solid organ transplantation

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World Journal of Clinical Cases 2024年第15期12卷 2542-2550页

作者： Xian-Quan Cui Lu-Wei Zhang Peng Zhao Jing-Jing Feng Department of Organ Transplantation Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina Department of Blood Purification Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina

BACKGROUND The number of patients undergoing solid organ transplantation has increased ***,infections in solid organ transplant recipients can have a severe effect on patient survival owing to the continued use of *** is a novel macrolide antibiotic produced by genetically engineered streptomyces spiramyceticus harboring a 4’’-O-isovaleryltransferase gene(ist)from streptomyces *** has good antibacterial and antiviral ***,no relevant studies have been conducted on the efficacy and safety of carrimycin in patients with severe pneumonia(SP)after solid organ *** To explore the efficacy and safety of carrimycin in patients with SP after solid organ transplantation to provide a medication reference for clinical *** In March 2022,ten patients with SP following solid-organ transplantation were treated at our hospital between January 2021 and March *** the condition was critical and difficult to control with other drugs,carrimycin was *** ten patients'clinical features and treatment protocols were retrospectively analyzed,and the efficacy and safety of carrimycin for treating SP following solid organ transplantation were *** All ten patients were included in the *** etiological agent detection,there were three cases of fungal pneumonia,two cases of bacterial pneumonia,two cases of Pneumocystis pneumonia,and three cases of mixed *** treatment with carrimycin,the disease in seven patients significantly improved,the course of the disease was significantly shortened,fever was quickly controlled,chest computed tomography was significantly improved,and oxygenation was significantly ***,the patients were discharged after *** patient died of acute respiratory distress syndrome,and two patients discontinued *** Carrimycin is a safe and effective treatment modality for SP following soli

关键词： Carrimycin Organ transplantation Severe pneumonia Immunosuppressant Infection Antiviral drugs

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KAT7/HMGN1 signaling epigenetically induces tyrosine phosphorylation-regulated kinase 1A expression to ameliorate insulin resistance in Alzheimer’s disease

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World Journal of Psychiatry 2024年第3期14卷 445-455页

作者： Qun-Shan Lu Lin Ma Wen-Jing Jiang Xing-Bang Wang Mei Lu Department of Geriatric Medicine Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina Key Laboratory of Cardiovascular Proteomics of shandong Province Qilu Hospital of Shandong UniversityJinan 250012Shandong ProvinceChina

BACKGROUND Epidemiological studies have revealed a correlation between Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2D).Insulin resistance in the brain is a common feature in patients with T2D and ***7 is a histone acetyltransferase that participates in the modulation of various *** To determine the effects of KAT7 on insulin patients with *** APPswe/PS1-dE9 double-transgenic and db/db mice were used to mimic AD and diabetes,*** in vitro model of AD was established by Aβ*** resistance was induced by chronic stimulation with high insulin *** expression of microtubule-associated protein 2(MAP2)was assessed using *** protein levels of MAP2,Aβ,dual-specificity tyrosine phosphorylation-regulated kinase-1A(DYRK1A),IRS-1,p-AKT,total AKT,p-GSK3β,total GSK3β,DYRK1A,and KAT7 were measured via western *** of reactive oxygen species(ROS),malondialdehyde(MDA),and SOD activity was measured to determine cellular oxidative *** cytometry and CCK-8 assay were performed to evaluate neuronal cell death and proliferation,*** RNA levels of KAT7 and DYRK1A were examined using quantitative PCR.A chromatin immunoprecipitation assay was conducted to detect H3K14ac in *** KAT7 expression was suppressed in the AD *** of KAT7 decreased Aβaccumulation and MAP2 expression in AD ***7 overexpression decreased ROS and MDA levels,elevated SOD activity in brain tissues and neurons,and simultaneously suppressed neuronal ***7 upregulated levels of p-AKT and p-GSK3βto alleviate insulin resistance,along with elevated expression of ***7 depletion suppressed DYRK1A expression and impaired H3K14ac of ***1 overexpression recovered DYRK1A levels and reversed insulin resistance caused by KAT7 *** We determined that KAT7 overexpression recovered insulin sensitivity in AD by recruiting HMGN1 to enhance DYRK1A acetylati

关键词： Alzheimer's disease Diabetes Insulin resistance KAT7 Dual-specificity tyrosine phosphorylation-regulated kinase-1A HMGN1

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Establishment and Validation of a Four-stress Granule-related Gene Signature in Hepatocellular Carcinoma

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Journal of Clinical and Translational Hepatology 2024年第1期12卷 1-14页

作者： Mengzhu Li Xiude Fan Jiajun Zhao Dawei Wang Department of Endocrinology Shandong Provincial HospitalShandong UniversityJinanShandongChina Key Laboratory of Endocrine Glucose&Lipids Metabolism and Brain Aging Ministry of EducationDepartment of EndocrinologyShandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandongChina shandong Key Laboratory of Endocrinology and Lipid Metabolism JinanShandongChina shandong Institute of Endocrine and Metabolic Diseases JinanShandongChina

Background and Aims:Stress granules(SGs)as membrane-less cytoplasmic foci formed in response to unfavorable external stimuli could promote cancer cells to adapt to hostile *** carcinoma(HCC)is prone to be highly aggressive once diagnosed,which markedly reduces patient survival ***,it is crucial to develop valid diagnostic markers to prognosticate HCC patient prognosis,which promotes individualized precision therapeutics in *** the pro-tumorigenic activity of SGs,it is of great potential value to construct a prognostic tool for HCC based on the expression profiles of SG-related genes(SGGs).Methods:Bioinformatic analysis was employed to establish an SGG-based prognostic *** blotting and realtime polymerase chain reaction assays were used to assess the expression patterns of the related ***-of-function experiments were performed to analyze the effect of the SGGs on SG formation and cell ***:A four-SGG signature(KPNA2,MEX3A,WDR62,and SFN)targeting HCC was established and validated to exhibit a robust performance in predicting HCC ***,all four genes were further found to be highly expressed in human HCC *** important,we demonstrated that individually knocking down the four SGGs significantly reduced HCC cell proliferation and metastasis by compromising the SG formation ***:We developed an SGG-based predictive signature that can be used as an independent prognostic tool for *** strong predictive power of this signature was further elucidated by the carcinogenic activity of KPNA2,MEX3A,WDR62,and SFN in HCC cells by regulating SG formation.

关键词： Hepatocellular carcinoma Stress granules Prognostic factor G3BP1

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Potential impact of specific therapy on pregnant women with pulmonary arterial hypertension without cardiac shunt:a descriptive study in northern China

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Emergency and Critical Care Medicine 2024年第2期4卷 60-66页

作者： Weida Lu Min Li Fuqing Ji Hua Feng Guo Li Qiushang Ji Hongyu Zhang Xiaopei Cui Department of Geriatric Medicine&shandong Key Laboratory Cardiovascular Proteomics Qilu Hospital of Shandong UniversityJinanShandongChina Intensive Care Unit of Cardiac Surgery Shandong Provincial Qianfoshan Hospitalthe First Hospital Affiliated with Shandong First Medical UniversityAffiliated Hospital of Shandong UniversityJinanShandongChina Department of Cardiology Linyi Central HospitalLinyiShandongChina Department of Gastroenterology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandongChina Department of Pulmonary and Critical Care Medicine the Affiliated Hospital of Qingdao UniversityQingdaoShandongChina Department of Cardiology Qilu Hospital of Shandong UniversityJinanShandongChina

Background:Pregnancy in women with pulmonary arterial hypertension(PAH)is a fatal condition,despite the effectiveness of PAH-specific *** coverage status and effect of specific therapies in pregnant patients with PAH without cardiac shunts in China remain *** investigate this issue,we conducted a multicenter retrospective study in northern ***:The study included 85 patients who were admitted to 4 clinical centers in shandong Province between October 2010 and August *** endpoint events included(1)maternal death and/or(2)major adverse cardiac events,both occurring during pregnancy or within 6 weeks ***:Although the overall mortality rate was encouraging(11.8%),the number of patients receiving PAH-specific therapies was extremely low(28.2%).Moreover,only 15.3%of patients received adequate duration of PAH-specific therapy(≥4 weeks)before delivery,and this subgroup showed the lowest major adverse cardiac events rate(7.7%)compared with that in the untreated(19.7%)and short-time treated groups(<4 weeks;54.5%).Conclusion:Pregnant patients with PAH without cardiac shunts face significantly increased mortality ***-term PAH-specific therapy does not guarantee favorable maternal *** screening,early identification,and timely intervention are expected to improve maternal outcomes in pregnant women with PAH.

关键词： Major adverse cardiac events Maternal mortality Pregnancy outcome Pulmonary arterial hypertension Specific therapy

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