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Bone-targeting engineered small extracellular vesicles carrying anti-miR-6359-CGGGAGC prevent valproic acid-induced bone loss

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Signal Transduction and Targeted Therapy 2024年第2期9卷 751-765页

作者： Xudong Xie Peng Cheng Liangcong Hu Wu Zhou Detai Zhang Samuel Knoedler Guodong Liu Yuan Xiong Hang Xue Yiqiang Hu Barbara Kern Doha Obed Adriana CPanayi Lang Chen Chenchen Yan Ze Lin Guandong Dai Bobin Mi Yingze Zhang Guohui Liu Department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430022China Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration Wuhan 430022China Department of Clinical Laboratory Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022P.R.China Division of Plastic surgery Brigham and Women’s HospitalHarvard Medical SchoolBostonMA 02152USA Department of Plastic surgery and Hand surgery Klinikum Rechts der IsarTechnical University of MunichMunichGermany Medical Center of Trauma and War Injuries Daping HospitalArmy Medical UniversityChonqing 400042China Department of Plastic surgery Campus CharitéMitte|Campus Virchow-KlinikumCharité-Universitätsmedizin Berlincorporate member of Freie Universität BerlinHumboldt-Universität zu Berlin and Berlin Institute of HealthBerlinGermany Berlin Institute of Health Charité-Universitätsmedizin BerlinBerlinGermany Department of Plastic AestheticHand and Reconstructive SurgeryHannover Medical SchoolHannoverGermany Department of Hand Plastic and Reconstructive SurgeryMicrosurgeryBurn CenterBG Trauma Center LudwigshafenUniversity of HeidelbergLudwig-Guttmann-Strasse 1367071 Ludwigshafen/RhineGermany Pingshan District People’s Hospital of Shenzhen Pingshan General Hospital of Southern Medical UniversityShenzhenGuangdong 518118China Department of Orthopaedic surgery The Third Hospital of Hebei Medical UniversityNO.139 Ziqiang RoadShijiazhuang 050051China

The clinical role and underlying mechanisms of valproic acid(VPA)on bone homeostasis remain ***,we confirmed that VPA treatment was associated with decreased bone mass and bone mineral density(BMD)in both patients and *** effect was attributed to VPA-induced elevation in osteoclast formation and *** RNA-sequencing,we observed a significant rise in precursor miR-6359 expression in VPA-treated osteoclast precursors in vitro,and further,a marked upregulation of mature miR-6359(miR-6359)in vivo was demonstrated using quantitative real-time PCR(qRT-PCR)and miR-6359 fluorescent in situ hybridization(miR-6359-FISH).Specifically,the miR-6359 was predominantly increased in osteoclast precursors and macrophages but not in neutrophils,T lymphocytes,monocytes and bone marrow-derived mesenchymal stem cells(BMSCs)following VPA stimulation,which influenced osteoclast differentiation and bone-resorptive ***,VPA-induced miR-6359 enrichment in osteoclast precursors enhanced reactive oxygen species(ROS)production by silencing the SIRT3 protein expression,followed by activation of the MAPK signaling pathway,which enhanced osteoclast formation and activity,thereby accelerating bone ***,there are no medications that can effectively treat VPA-induced bone ***,we constructed engineered small extracellular vesicles(E-sEVs)targeting osteoclast precursors in bone and naturally carrying anti-miR-6359 by introducing of EXOmotif(CGGGAGC)in the 3’-end of the anti-miR-6359 *** confirmed that the E-sEVs exhibited decent bone/osteoclast precursor targeting and exerted protective therapeutic effects on VPA-induced bone loss,but not on ovariectomy(OVX)and glucocorticoid-induced osteoporotic models,deepening our understanding of the underlying mechanism and treatment strategies for VPA-induced bone loss.

关键词： miR protective stimulation

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Plexin domain-containing 1 may be a biomarker of poor prognosis in hepatocellular carcinoma patients,may mediate immune evasion

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2091-2112页

作者： Ming-Yue Tang Xue Shen Run-Sheng Yuan Hui-Yuan Li Xin-Wei Li Yi-Ming Jing Yue Zhang Hong-Hong Shen Zi-Shu Wang Lei Zhou Yun-Chuan Yang He-Xin Wen Fang Su Department of Medical Oncology The First Affiliated Hospital of Bengbu Medical CollegeBengbu 233000Anhui ProvinceChina Otolaryngology and Head and Neck surgery The First Affiliated Hospital of Bengbu Medical CollegeBengbu 233000Anhui ProvinceChina Department of Neurology The First Affiliated Hospital of Bengbu Medical CollegeBengbu 233000Anhui ProvinceChina Department of Hepatobiliary surgery The First Affiliated Hospital of Bengbu Medical CollegeBengbu 233000Anhui ProvinceChina Department of Gastrointestinal surgery The First Affiliated Hospital of Bengbu Medical CollegeBengbu 233000Anhui ProvinceChina

BACKGROUND For the first time,we investigated the oncological role of plexin domain-containing 1(PLXDC1),also known as tumor endothelial marker 7(TEM7),in hepatocellular carcinoma(HCC).AIM To investigate the oncological profile of PLXDC1 in *** Based on The Cancer Genome Atlas database,we analyzed the expression of PLXDC1 in *** immunohistochemistry,quantitative real-time polymerase chain reaction(qRT-PCR),and Western blotting,we validated our *** prognostic value of PLXDC1 in HCC was analyzed by assessing its correlation with clinicopathological features,such as patient survival,methylation level,tumor immune microenvironment features,and immune cell surface checkpoint ***,to assess the immune evasion potential of PLXDC1 in HCC,we used the tumor immune dysfunction and exclusion(TIDE)website and immunohistochemical staining *** Based on immunohistochemistry,qRT-PCR,and Western blot assays,overexpression of PLXDC1 in HCC was associated with poor *** and multivariate Cox analyses indicated that PLXDC1 might be an independent prognostic *** HCC patients with high methylation levels,the prognosis was worse than in patients with low methylation *** enrichment analysis of HCC tissues indicated that genes upregulated in the high-PLXDC1 subgroup were enriched in mesenchymal and immune activation signaling,and TIDE assessment showed that the risk of immune evasion was significantly higher in the high-PLXDC1 subgroup compared to the low-PLXDC1 *** high-risk group had a significantly lower immune evasion rate as well as a poor prognosis,and PLXDC1-related risk scores were also associated with a poor *** As a result of this study analyzing PLXDC1 from multiple biological perspectives,it was revealed that it is a biomarker of poor prognosis for HCC patients,and that it plays a role in determining immune evasion status.

关键词： Plexin domain-containing 1 Biomarker Immune evasion Prognosis Immunotherapy Hepatocellular carcinoma

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Asymptomatic low-grade appendiceal mucinous neoplasm:A case report

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World Journal of Clinical Cases 2024年第2期12卷 361-366页

作者： Min-Quan Yao Yu-Peng Jiang Yuan-Yu Wang Yi-Ping Mou Jin-Xing Fan Department of Gastrointestinal surgery Tongxiang First People’s HospitalJiaxing 314500Zhejiang ProvinceChina Department of General surgery Zhejiang Provincial People’s HospitalHangzhou 310014Zhejiang ProvinceChina Endoscopy Center Tongxiang First People’s HospitalJiaxing 314500Zhejiang ProvinceChina

BACKGROUND Low-grade appendiceal neoplasms(LAMN)are characterized by low incidence and atypical clinical presentations,often leading to misdiagnosis as acute or chronic appendicitis before *** primary diagnostic tool for LAMN is abdominal computed tomography(CT)*** resection remains the cornerstone of LAMN management,necessitating en bloc tumor excision to minimize the risk of iatrogenic ***,known for its minimal invasiveness,reduced postoperative discomfort,and expedited recovery,is a safe and reliable approach for LAMN *** the possibility of pseudomyxoma peritonei development,appendectomy and partial appendectomy generally result in negative tumor margins and favorable outcomes,which can be attributed to the disease’s slow growth and lower *** SUMMARY A 71-year-old male patient was admitted to our hospital with a pelvic spaceoccupying lesion detected 1 mo *** examination showed a soft abdomen without tenderness or rebound and no palpable *** shifting dullness was noted,and digital rectal examination revealed no palpable *** revealed a raised,smooth-surfaced mass measuring 3.0 cm in the *** contrast-enhanced CT showed a markedly thickened and dilated appendix with visible cystic *** surgery was performed and revealed a significantly dilated appendix,leading to laparoscopic resection of the appendix and part of the ***-surgical pathologic analysis confirmed *** patient received symptomatic and supportive post-operative care and was discharged on postoperative day 4 without complications such as abdominal bleeding,intestinal obstruction,or incision *** tumor recurrence was observed during a 7-mo follow-up *** LAMN is a rare disease that lacks specific clinical *** CT plays a crucial role in diagnosing LAMN,and laparoscopic surgery is a safe and effective diagnostic and therapeutic approach.

关键词： Low-grade appendiceal mucinous neoplasm Pseudomyxoma peritonei Computed tomography Laparoscopy appendectomy Case report

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Longitudinal gut fungal alterations and potential fungal biomarkers for the progression of primary liver disease

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Science China(Life Sciences) 2024年第6期67卷 1183-1198页

作者： Shiman Jiang Lvwan Xu Yanfei Chen Zheyue Shu Longxian Lv Yuxi Zhao Kefan Bi Sisi Yang Qiangqiang Wang Lanjuan Li State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious DiseasesNational Medical Center for Infectious DiseasesCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Division of Hepatobiliary and Pancreatic surgery Department of SurgeryThe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China

Liver disease,a major health concern worldwide,is a serious and progressive ***,we not only established a mouse model of DEN+CCl4-induced primary liver disease but also collected clinical human samples to investigate longitudinal alterations in the gut *** liver disease advanced,gut integrity was disrupted,and the mycobiota was disturbed in the mouse *** metabolites associated with hepatocellular carcinoma(HCC)differed from those associated with the cirrhotic phase as follows:levels of stercobilin and aflatoxin B1 dialcohol were reduced,while levels of triterpenoids,bafilomycin A1,and DHEA were increased in the HCC *** abundance of the phylum Chytridiomycota increased as the chronic liver disease progressed and was then replaced by the phylum Ascomycota in *** on the results from clinical human samples,the genus Candida(Ascomycota)(in humans)and the genus Kazachstania(Ascomycota)(in mice)occupied a dominant position in the HCC group,while other fungi were *** increased abundance of *** and depletion of *** may be hallmarks of the progression of liver cirrhosis to early ***,the administration of *** and *** in the LC-HCC progression could accelerate or retard the progression of ***,gut fungi have the potential to serve as a noninvasive clinical biomarker and even a treatment method.

关键词： gut mycobiome liver disease longitudinal studies hepatocarcinogenesis fungal biomarker

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Efficacy and safety of clarithromycin for patients with sepsis or septic shock:a systematic review and meta-analysis

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Emergency and Critical Care Medicine 2024年第2期4卷 90-96页

作者： Pengyue Zhao Renqi Yao Jiaqi Yang Wei Wen Yongming Yao Xiaohui Du Department of General surgery First Medical Center of the Chinese PLA General HospitalBeijingChina Translational Medicine Research Center Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General HospitalBeijingChina Department of Burn surgery the First Affiliated Hospital of Naval Medical UniversityShanghaiChina Department of General surgery Hainan Hospital of Chinese PLA General HospitalSanyaHainanChina

Background:Clarithromycin exerts an immunomodulatory role in several human ***,whether this effect improves the prognosis in patients with sepsis remains controversial,and higher levels of clinical evidence are urgently *** the best of our knowledge,no meta-analysis to date has reported the clinical efficacy and safety of clarithromycin in ***:A comprehensive literature search of PubMed,EMBASE,and the Cochrane Library was conducted up to December 31,*** randomized controlled trials comparing the clinical efficacy and safety of clarithromycin with controls among patients with sepsis or septic shock were *** were pooled by applying a fixed-effects model and a relative risk(RR)estimate with 95%confidence intervals(CIs)using Review Manager(version 5.3;Cochrane Collaboration,Copenhagen,Denmark).Results:Three randomized controlled trials involving a total of 910 patients were *** pooled results confirmed that clarithromycin had no beneficial effect on progression to multiple organ dysfunction syndrome(RR:1.51;95%CI:1.02-2.25;P=0.04;I^(2)=0%),28-day mortality(RR:1.09;95%CI:0.87-1.36;P=0.46;I^(2)=0%),and 90-day mortality(RR:0.86;95%CI:0.71-1.03;P=0.10;I^(2)=81%)in patients with sepsis or septic ***,there was no difference in other serious adverse events between patients who received clarithromycin and those in the control group(RR:1.02;95%CI:0.87-1.19;P=0.83;I^(2)=18%).Conclusion:Our meta-analysis did not reveal an improvement to short-term outcomes in patients with sepsis treated with ***,administration of clarithromycin did not increase the risk of adverse events.

关键词： Clarithromycin Meta-analysis Outcomes Sepsis Septic shock

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Long-term olfactory loss post-COVID-19:Pathobiology and potential therapeutic strategies

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World Journal of Otorhinolaryngology-Head and Neck surgery 2024年第2期10卷 148-155页

作者： Sarah Kim John B.Finlay Tiffany Ko Bradley J.Goldstein Department of Head and Neck surgery&Communication Sciences Duke UniversityDurhamNorth CarolinaUSA Medical Scientist Training program Duke UniversityDurhamNorth CarolinaUSA Department of Neurobiology Duke UniversityDurhamNorth CarolinaUSA

An acute loss of smell emerged as a striking symptom present in roughly half of the people infected with the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)virus in the early phases of the COVID-19 *** most COVID-19 patients,olfaction recovers over the course of a few ***,a lasting partial or complete loss of smell,often associated with distorted olfactory perceptions termed parosmia,has emerged as a widespread problem impacting at least 5%-10%of those who experience anosmia due to *** inability to offer effective therapies to this hyposmic or anosmic population,comprising millions of patients,highlights an enormous unmet need for the medical ***,we summarize the current understanding of the pathobiology causing acute olfactory loss due to SARS-CoV-2 infection,focusing on how the virus interacts with the peripheral olfactory system,a major site of viral *** also explore the problem of long-COVID olfactory dysfunction,which may accompany other persistent systemic disorders collectively termed postacute sequelae of ***,we discuss an emerging model focused on unresolved immune cell activity driving ongoing ***,we review current and future therapeutic approaches aimed at restoring olfactory function.

关键词： hyposmia inflammation long-COVID parosmia

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中国胃癌肝转移患者临床诊疗特征及预后分析:全国多中心队列研究(RECORD研究)

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Science Bulletin 2024年第3期69卷 303-307页

作者：高云鹤郗洪庆商亮唐兆庆卫勃乔治唐云王鑫鑫周静汪学非黄昌明陆俊李国新余江梁延锐季加孚李子禹薛侃梁寒柯彬臧潞何子锐谢少华黄华徐泽宽田艳涛熊建平李佶阳崔秋霞李力卢婷婷宋奇嬴刘诗贺孙益红李乐平陈凛 RECORD研究协作组 Section of Gastric surgery Senior Department of General SurgeryThe First Medical CenterChinese PLA General HospitalBeijing 100853China Section of Abdominal Trauma surgery Senior Department of General SurgeryThe First Medical CenterChinese PLA General HospitalBeijing 100853China Institute of General surgery The First Medical CenterChinese PLA General HospitalBeijing 100853China Department of Gastrointestinal surgery Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021China Department of General surgery Fudan University Zhongshan HospitalShanghai 200032China Department of General surgery Fujian Medical University Union HospitalFuzhou 350001China Department of General surgery Nanfang Hospital Affiliated to Southern Medical UniversityGuangzhou 510515China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education) Gastrointestinal Cancer CenterPeking University Cancer Hospital&InstituteBeijing 100142China Department of Gastric Cancer surgery Tianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of General surgery Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Institute of Population Medicine and School of Public Health Fujian Medical UniversityFuzhou 350122China Department of Gastric surgery Fudan University Shanghai Cancer CenterShanghai 200032China Department of General surgery Jiangsu Province HospitalNanjing Medical UniversityNanjing 210029China Department of Pancreatic and Gastric surgery National Cancer CenterNational Clinical Research Center for CancerCancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100029China

Despite surgical improvements and pharmacological advances,management of late-stage gastric cancer patients,especially those with hepatic metastasis remains challenging[1–3].Although nationwide registry data from SEER(Surveillance,Epidemiology,and End Results)[4]and the Nordic database[5]in Western countries have provided epidemiological information for patients with gastric cancer liver metastasis(GCLM),little is known about the detailed clinical characteristics.

关键词：胃癌肝转移 metastasis cancer

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TGF-βsignaling in health,disease,and therapeutics

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1466-1505页

作者： Ziqin Deng Tao Fan Chu Xiao He Tian Yujia Zheng Chunxiang Li Jie He Department of Thoracic surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China

ransforming growth factor(TGF)-βis a multifunctional cytokine expressed by almost every tissue and cell *** signal transduction of TGF-βcan stimulate diverse cellular responses and is particularly critical to embryonic development,wound healing,tissue homeostasis,and immune homeostasis in *** dysfunction of TGF-βcan play key roles in many diseases,and numerous targeted therapies have been developed to rectify its pathogenic *** the past decades,a large number of studies on TGF-βsignaling have been carried out,covering a broad spectrum of topics in health,disease,and ***,a comprehensive overview of TGF-βsignaling is required for a general picture of the studies in this *** this review,we retrace the research history of TGF-βand introduce the molecular mechanisms regarding its biosynthesis,activation,and signal *** also provide deep insights into the functions of TGF-βsignaling in physiological conditions as well as in pathological ***-β-targeting therapies which have brought fresh hope to the treatment of relevant diseases are *** the summary of previous knowledge and recent updates,this review aims to provide a systematic understanding of TGF-βsignaling and to attract more attention and interest to this research area.

关键词： homeostasis healing wound

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Genetic landscape and clinical significance of cuproptosis-related genes in liver hepatocellular carcinoma

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Genes & Diseases 2024年第2期11卷 516-519页

作者： Dingtao Hu Yichuan Wang Xu Shen Tiantian Mao Xijun Liang Tengjiao Wang Weifeng Shen Yugang Zhuang Jin Ding Clinical Cancer Institute Center for Translational MedicineNaval Medical UniversityShanghai 200433China Department of Emergency Shanghai Tenth People's HospitalTongji UniversitySchool of MedicineShanghai 200072China Bioinformatics Analysis Laboratory Center for Translational MedicineNaval Medical UniversityShanghai 200433China The Department of Hepatic surgery Eastern Hepatobiliary Surgery HospitalNaval Medical UniversityShanghai 200433China

Recently,Peter et al reported a novel form of cell death(cuproptosis)that was different from other known death mechanisms.1 They found that accumulation of copper ions could induce destabilization of Fe-S cluster proteins and aggregation of mitochondrial lipoylated proteins,ultimately resulting in cuproptosis.1 of note,ten genes were identified as cuproptosis-related genes(CRGs)in copper ion-induced cell death,including PDHB,PDHA1,DLAT,DLD,LIPT1,LIAS,FDX1,CDKN2A,GLS,and MTF1.1 Since dysregulation of copper metabolism is involved in many cancers,cuproptosis and CRGs may play vital roles in cancer development and treatment.1.2 Herein,our pancancer analysis revealed the coordinated upregulation of 9 of 10 CRGs in human liver hepatocellular carcinoma(LIHC)across 33 solid tumors(Fig.S1A;Fig.1A),suggesting the distinct role of CRGs in *** then explored the genetic landscape,biological function,and clinical significance of CRGs in LIHC,and validated our bioinformatic findings by in vitro experiments and clinical *** detailed methods were described in the supplementary material.

关键词： clinical metabolism hepatocellular

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Carotid versus axillary artery cannulation for descending aorta remodeling in type A acute aortic dissection

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World Journal of Cardiology 2024年第10期16卷 564-573页

作者： Qin Jiang Tao Yu Ke-Li Huang Ke Liu Xi Li Sheng-Shou Hu Department of Cardiac surgery Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610072Sichuan ProvinceChina Cardiac surgery Center Sichuan Academy of Medical Sciences&Sichuan Provincial People’s HospitalChengdu 610072Sichuan ProvinceChina

BACKGROUND Arterial cannulation sites for the surgical repair of type A aortic dissection(AAD)have evolved from right axillary artery(AA)cannulation to bilateral carotid artery(CA)based of femoral artery(FA)*** descending aorta remodeling is closely linked to the false lumen area ratio(FLAR),defined as false lumen area/aortic area,as well as to the incidence of renal replacement therapy(RRT).AIM To investigate the effect of the updated arterial cannulation strategy on descending aortic *** A total of 443 AAD patients who received FA combined cannulation between March 2015 and March 2023 were included in the *** these,209 received right AA cannulation and 234 received bilateral CA *** primary outcome was the change in FLAR,as calculated from computed tomography angiography in three segments of the descending aorta:Thoracic(S1),upper abdominal(S2),and lower abdominal(S3).Secondary outcomes were the incidence of RRT and the serum inflammation response,as observed by the levels of high sensitivity C reaction protein(hs-CRP)and Interleukin-6(IL-6).RESULTS The postoperative/preoperative ratio of FLAR in S2 and S3 was higher in the AA group compared to the CA group(S2:0.80±0.08 vs 0.75±0.07,P<0.001;S3:0.57±0.12 vs 0.50±0.12,P<0.001,respectively).The AA group also had a significantly higher incidence of RRT(19.1%vs 8.5%,P=0.001;odds ratio:2.533,95%CI:1.427-4.493)and higher levels of inflammation cytokines 24 h after the procedure[hr-CRP:117±17 vs 104±15 mg/L;IL-6:129(103,166)vs 83(69,101)pg/mL;both P<0.001]compared to the CA *** The CA cannulation strategy was associated with better abdominal aorta remodeling after AAD repair compared to AA cannulation,as observed by a greater change in FLAR and lower incidence of RRT.

关键词： Acute type A aortic dissection Bilateral carotid arterial cannulation Descending aortic remodeling False lumen area ratio Prognosis

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