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Effect of autologous bone marrow stem cells-scaffold transplantation on the ongoing pregnancy rate in intrauterine adhesion women:a randomized,controlled trial

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Science China(Life Sciences) 2024年第1期67卷 113-121页

作者： Hui Zhu Taishun Li Peizhen Xu Lijun Ding Xianghong Zhu Bin Wang Xiaoqiu Tang Juan Li Pengfeng Zhu Huiyan Wang Chenyan Dai Haixiang Sun Jianwu Dai Yali Hu Department of Obstetrics and Gynecology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Department of Biostatistics Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Department of Gynecology Changzhou Maternal and Child Health Care HospitalChangzhou Medical CenterNanjing Medical UniversityChangzhou 213004China Clinical Center for Stem Cell Research Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Department of Hematology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008China Institute of Genetics and Developmental Biology Chinese Academy of SciencesBeijing 100190China

Intrauterine adhesion is a major cause of female reproductive *** we and others uncontrolled pilot studies showed that treatment with autologous bone marrow stem cells made a few patients with severe intrauterine adhesion obtain live birth,no large sample randomized controlled studies on this therapeutic strategy in such patients have been reported so *** verify if the therapy of autologous bone marrow stem cells-scaffold is superior to traditional treatment in moderate to severe intrauterine adhesion patients in increasing their ongoing pregnancy rate,we conducted this randomized controlled clinical *** 195 participants with moderate to severe intrauterine adhesion were screened and 152 of them were randomly assigned in a 1:1 ratio to either group with autologous bone marrow stem cells-scaffold plus Foley balloon catheter or group with only Foley balloon catheter(control group)from February 2016 to January *** per-protocol analysis included 140 participants:72 in bone marrow stem cells-scaffold group and 68 in control *** ongoing pregnancy occurred in 45/72(62.5%)participants in the bone marrow stem cells-scaffold group which was significantly higher than that in the control group(28/68,41.2%)(RR=1.52,95%CI 1.08–2.12,P=0.012).The situation was similar in live birth rate(bone marrow stem cells-scaffold group 56.9%(41/72)*** group 38.2%(26/68),RR=1.49,95%CI 1.04–2.14,P=0.027).Compared with control group,participants in bone marrow stem cells-scaffold group showed more menstrual blood volume in the 3rd and 6th cycles and maximal endometrial thickness in the 6th cycle after hysteroscopic *** incidence of mild placenta accrete was increased in bone marrow stem cells-scaffold group and no severe adverse effects were *** conclusion,transplantation of bone marrow stem cells-scaffold into uterine cavities of the participants with moderate to severe intrauterine adhesion increased their ongoing pregnancy and

关键词： intrauterine adhesion Asherman’s syndrome uterine infertility autologous bone marrow stem cells transplantation endometrial regeneration ongoing pregnancy rate

The role of gut microbiota associated metabolites in digestive disorders

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Engineered Regeneration 2024年第2期5卷 228-246页

作者： Na Li Cheng Zhao Pingnan Zhang Songting Wu Xiaotan Dou Saifei Xu Xiaoqi Zhang Chunyan Peng Ying Xie Shuling Huang Lin Zhou Yonghua Shen Lei Wang Jinglin Wang Chenggong Yu Department of Gastroenterology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing210008China Division of Hepatobiliary and Transplantation Surgery Department of Gernal SurgeryNanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing210008China

The gut has been a focal point in the research of digestive system *** internal microbiota generates metabolites that function as signaling molecules and substrates,interacting with the intestinal wall and influ-encing host physiology and ***,the gut microbiota and metabolites owe highly diverse types and quantities,posing challenges for quantitative analysis,and monitoring frequent interactions between diges-tive tract metabolites and the intestinal wall remains a ***,research targeting gut microbiota metabolites has elucidated their relevance to digestive *** modulating metabolites such as short-chain fatty acids,bile acids,and lipopolysaccharides,it is possible to intervene in the progression of diseases such as inflammatory bowel disease and non-alcoholic fatty liver ***,research on gut microbiota is advancing,and more work is required to explore the interactions between host,microbes and underlying *** this review,we have revisited the generation of gut microbiota-related metabolites,their impact on diseases,and modes of interaction,emphasizing the significant role of metabolites in digestive system *** is believed that the linkage between gut microbiota and diseases in current research can be established through metabolites,providing a framework and foundation for research in the field of metabolomics and fundamental mechanisms.

关键词： Gut microbial metabolites Digestive disorders Inflammatory bowel disease(IBD) Non-alcoholic fatty liver disease(NAFLD)

Protective and Adverse Roles of DDX3X in Different Cell Types in Nonalcoholic Steatohepatitis Progression

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Research 2024年第3期6卷 561-574页

作者： Suzhen Yang Lin Zhou Tianming Zhao Hanlong Zhu Tingting Luo Kang Jiang Xiaoxiao Shi Chunyan Chen Han Zhang Si Zhao Xiaoping Zou Yuzheng Zhuge Fangyu Wang Lei Wang Mingzuo Jiang Bing Xu Department of Gastroenterology the Affiliated Drum Tower Hospital of Nanjing University Medical SchoolJiangsuNanjing210002China. Department of Gastroenterology and Hepatology the Affiliated Jinling Hospital of Nanjing University Medical SchoolJiangsuNanjing210002China school of Medicine Northwest UniversityShaanxiXi’an710069China. Department of Gastroenterology Nanjing Drum Tower HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeJiangsuNanjing210008China.

Persistent hepatic cellular metabolic stress and liver inflammatory stimuli are key signatures of nonalcoholic steatohepatitis(NASH).DDX3X is a vital molecule involved in cell fate decisions in both pro-survival stress granule(SG)and pro-death NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome assembly in response to stress ***,the role of DDX3X in NASH remains *** characterized the cell type-specific roles of DDX3X in *** liver tissues from NASH patients and normal control subjects were collected to assess DDX3X expression and *** steatohepatitis models were constructed by feeding macrophage-specific DDX3X knockout(DDX3^(XΔMφ)),hepatocyte-specific DDX3X knockout(DDX3X^(Δhep)),and wild-type control(DDX3X^(fl/fl))mice a high-fat and high-cholesterol(HFHC)diet,a methionine-and choline-deficient(MCD)diet,and a high-fat/high-iron/high-fructose/high-cholesterol,low-methionine,and choline-deficient(HFHIHFHC-MCD)*** study demonstrated that DDX3X was predominantly expressed in macrophages and hepatocytes in control liver tissues,and its expression was down-regulated in patients or mice with *** to DDX3X^(fl/fl) littermates,DDX3^(XΔMφ)mice showed improved liver histology in nutritional steatohepatitis *** of macrophage DDX3X inhibited NLRP3 inflammasome-mediated pyroptosis,causing anti-inflammatory M2 polarization and alleviating hepatocyte steatohepatitic ***3X^(Δhep) mice developed marked steatohepatitis in multiple nutritional steatohepatitis models compared to DDX3X^(fl/fl) ***3X-deleted hepatocytes showed impaired SG assembly,leading to increased sensitivity and intolerance to metabolic stimulation and resultant *** conclusion,DDX3X plays opposite roles in different cell types during the progression of NASH.A better understanding of the cell-specific differences in the crosstalk between SG formation and NLRP3 activation is crucial for developing pr

关键词： NLRP3 impaired inhibited

The diagnostic value of tenascin-C in acute aortic syndrome

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Journal of Geriatric Cardiology 2024年第3期21卷 359-368页

作者： Ming MA Wei CHEN Hai-Long CAO Jun PAN Qing ZHOU Xin-Long TANG Dong-Jin WANG Department of Thoracic and Cardiovascular Surgery Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityNanjingChina Department of Thoracic and Cardiovascular Surgery Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingChina Department of Thoracic surgery Kunshan Hospital of Traditional Chinese MedicineJiangsuChina

OBJECTIVES Misdiagnosis of acute aortic syndrome(AAS)significantly increases ***-C(TN-C)is an extracellular matrix glycoprotein related to cardiovascular *** elevation of TN-C in AAS and whether it can discriminate suddenonset of acute chest pain in Chinese remains *** We measured the plasma concentration of TN-C by ELISA in a cohort of 376 patients with chest or back *** to discriminate AAS from acute coronary syndrome(ACS)were compared and *** From October 2016 to September 2021,376 undiagnosed patients with chest or back pain were enrolled.166 of them were finally diagnosed as AAS,100 were ACS and 110 without cardiovascular diseases(NCV).TN-C was significantly elevated in AAS at 18.18 ng/mL(IQR:13.10–27.68)compared with 7.51 ng/mL(IQR:5.67–11.38)in ACS(P<0.001)and 3.68 ng/mL(IQR:2.50–5.29)in NCV(P<0.001).There was no significant difference in TN-C level among the subtypes of *** the 166 AAS patients,the peaked level of TN-C was at acute stage(P=0.012),then a slight of decrease was observed at subacute *** area under receiver operating characteristic curve for AAS patients versus NCV was 0.979(95%CI:0.964-0.994)for *** a cutoff level of 11.474 ng/mL,TN-C has a sensitivity of 76.0%,specificity of 85.5%,accuracy of 82.0%,positive predictive value(PPV)of 76.0%,negative predictive value(NPV)of 85.5%.Diagnostic performance of TN-C was superior to D-dimer and *** The concentration of serum TN-C in AAS patients was significantly higher than that in ACS patients and ***-C could be a new biomarker to distinguish AAS patients in the early stage after symptoms onset from other pain diseases.

关键词： acute cardiovascular elevated

Preoperative controlling nutritional status as an optimal prognostic nutritional index to predict the outcome for colorectal cancer

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 343-353页

作者： Li-Xiang Liu Hao Wang Bo Gao Ting-Ting Xu Qing-Gang Yuan Shi-Zhen Zhou Chao Ding Ji Miao Wen-Xian Guan Department of General Surgery Nanjing Drum Tower HospitalNanjing Drum Tower Hospital Clinical CollegeNanjing Medical UniversityNanjing 210008Jiangsu ProvinceChina Department of General Surgery Nanjing Drum Tower HospitalThe Affiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008Jiangsu ProvinceChina Department of Clinical Nutrition Nanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008Jiangsu ProvinceChina school of Chinese Materia Medica Nanjing University of Chinese MedicineNanjing 210008Jiangsu ProvinceChina Department of General Surgery Nanjing Drum Tower Clinical College of Xuzhou Medical UniversityNanjing 210008Jiangsu ProvinceChina

BACKGROUND The controlling nutritional status(CONUT)score effectively reflects a patient’s nutritional status,which is closely related to cancer *** study invest-igated the relationship between the CONUT score and prognosis after radical surgery for colorectal cancer,and compared the predictive ability of the CONUT score with other *** To analyze the predictive performance of the CONUT score for the survival rate of colorectal cancer patients who underwent potentially curative *** This retrospective analysis included 217 patients with newly diagnosed *** CONUT score was calculated based on the serum albumin level,total lymphocyte count,and total cholesterol *** cutoff value of the CONUT score for predicting prognosis was 4 according to the Youden Index by the receiver operating characteristic *** associations between the CONUT score and the prognosis were performed using Kaplan-Meier curves and Cox regression *** Using the cutoff value of the CONUT score,patients were stratified into CONUT low(n=189)and CONUT high groups(n=28).The CONUT high group had worse overall survival(OS)(P=0.013)and relapse-free survival(RFS)(P=0.015).The predictive performance of CONUT was superior to the modified Glasgow prognostic score,the prognostic nutritional index,and the neutrophil-to-lymphocyte ***,the predictive performances of CONUT+tumor node metastasis(TNM)stage for 3-year OS[area under the receiver operating characteristics curve(AUC)=0.803]and 3-year RFS(AUC=0.752)were no less than skeletal muscle mass index(SMI)+TNM *** CONUT score was negatively correlated with SMI(P<0.01).CONCLUSION As a nutritional indicator,the CONUT score could predict long-term outcomes after radical surgery for colorectal cancer,and its predictive ability was superior to other *** correlation between the CONUT score and skeletal muscle may be one of the factors that play a predictive role.

关键词： Controlling nutritional status Colorectal cancer Prognostic marker Sarcopenia Skeletal muscle

Transjugular intrahepatic portosystemic shunt:A promising therapy for recompensation in cirrhotic patients

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World Journal of Gastroenterology 2024年第16期30卷 2285-2286页

作者： Ya-Ni Jin Wei Zhang Department of Gastroenterology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing 210000Jiangsu ProvinceChina

This is a retrospective study focused on recompensation after transjugular intrahepatic portosystemic shunt(TIPS)*** authors confirmed TIPS could be a treatment for recompensation of patients with cirrhosis according to Baveno *** paper identified age and post-TIPS portal pressure gradient as independent predictors of recompensation in patients with decompensated cirrhosis after *** results need to be validated in a larger prospective cohort.

关键词： Cirrhosis recompensation Transjugular intrahepatic portosystemic shunt Portal pressure gradient Predictor factor Baveno VII

MFG-E8 Alleviates Cognitive Impairments Induced by Chronic Cerebral Hypoperfusion by Phagocytosing Myelin Debris and Promoting Remyelination

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Neuroscience Bulletin 2024年第4期40卷 483-499页

作者： Xiaohong Dong Zhi Zhang Xin Shu Zi Zhuang Pinyi Liu Renyuan Liu Shengnan Xia Xinyu Bao Yun Xu Yan Chen Department of Neurology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing210008China Department of Neurology Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjing210008China Department of Neurology Drum Tower Hospital of Nanjing Medical UniversityNanjing210008China Jiangsu Key Laboratory for Molecular Medicine Medical School of Nanjing UniversityNanjing210008China Jiangsu Provincial Key Discipline of Neurology Nanjing210008China

Chronic cerebral hypoperfusion is one of the pathophysiological mechanisms contributing to cognitive decline by causing white matter *** phagocytosing myelin debris in a timely manner can promote remyelination and contribute to the repair of white ***,milk fat globule-epidermal growth factor-factor 8(MFG-E8),a microglial phagocytosis-related protein,has not been well studied in hypoperfusion-related cognitive *** found that the expression of MFG-E8 was significantly decreased in the brain of mice after bilateral carotid artery stenosis(BCAS).MFG-E8 knockout mice demonstrated more severe BCAS-induced cognitive impairments in the behavioral *** addition,we discovered that the deletion of MFG-E8 aggravated white matter damage and the destruction of myelin microstructure through fluorescent staining and electron ***,MFG-E8 overexpression by AAV improved white matter injury and increased the number of mature oligodendrocytes after ***,in vitro and in vivo experiments showed that MFG-E8 could enhance the phagocytic function of microglia via theαVβ3/αVβ5/Rac1 pathway and IGF-1 production to promote the differentiation of oligodendrocyte progenitor cells into mature ***,we found that MFG-E8 was mainly derived from astrocytes,not *** findings suggest that MFG-E8 is a potential therapeutic target for cognitive impairments following cerebral hypoperfusion.

关键词： White matter injury Cognitive dysfunction MFG-E8 Remyelination Microglial phagocytosis

Phosphatidic acid-enabled MKL1 contributes to liver regeneration:Translational implication in liver failure

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Acta Pharmaceutica Sinica B 2024年第1期14卷 256-272页

作者： Jiawen Zhou Xinyue Sun Xuelian Chen Huimin Liu Xiulian Miao Yan Guo Zhiwen Fan Jie Li Yong Xu Zilong Li State Key Laboratory of Natural Medicines Department of PharmacologyChina Pharmaceutical UniversityNanjing 211198China Institute of Biomedical Research Liaocheng UniversityLiaocheng 252200China Department of Pathology Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical SchoolNanjing 210008China Department of Infectious Diseases Nanjing Drum Tower Hospital Affiliated with Nanjing University Medical SchoolNanjing 210008China Institute of Viruses and Infectious Diseases Nanjing UniversityNanjing 210008China

Liver regeneration following injury aids the restoration of liver mass and the recovery of liver *** the present study we investigated the contribution of megakaryocytic leukemia 1(MKL1),a transcriptional modulator,to liver *** report that both MKL1 expression and its nuclear translocation correlated with hepatocyte proliferation in cell and animal models of liver regeneration and in liver failure *** with MKL1 deletion exhibited defective regenerative response in the *** analysis revealed that MKL1 interacted with E2F1 to program pro-regenerative ***2 mediated phosphorylation primed MKL1 for its interaction with *** interest,phospholipase d2 promoted MKL1 nuclear accumulation and liver regeneration by catalyzing production of phosphatidic acid(PA).PA administration stimulated hepatocyte proliferation and enhanced survival in a MKL1-dependent manner in a pre-clinical model of liver ***,PA levels was detected to be positively correlated with expression of pro-regenerative genes and inversely correlated with liver injury in liver failure *** conclusion,our data reveal a novel mechanism whereby MKL1 contributes to liver *** for small-molecule compounds boosting MKL1 activity may be considered as a reasonable approach to treat acute liver failure.

关键词： Liver failure Liver regeneration Transcription regulation Transcription factor Hepatocytes Phosphatidic acid Phospholipase d2 Translational medicine

GM-CSF Promotes the Development of Dysfunctional Vascular Networks in Moyamoya Disease

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Neuroscience Bulletin 2024年第4期40卷 451-465页

作者： Huiqin Li Xiang Cao Xinya Gu Mengqi Dong Lili Huang Chenglu Mao Shengnan Xia Haiyan Yang Xinyu Bao Yongbo Yang Yun Xu Department of Neurology and Neurosurgery Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjing210008China Department of Neurology and Neurosurgery Nanjing Drum Tower HospitalState Key Laboratory of Pharmaceutical Biotechnology and Institute of Translational Medicine for Brain Critical DiseasesNanjing UniversityNanjing210008China Department of Neurology and Neurosurgery Nanjing Drum Tower Hospital Clinical College of Xuzhou Medical UniversityNanjing210008China Department of Neurology and Neurosurgery Nanjing Drum Tower Hospital Clinical College of Nanjing Medical UniversityNanjing210008China Jiangsu Key Laboratory for Molecular Medicine Medical School of Nanjing UniversityNanjing210008China Jiangsu Provincial Key Discipline of Neurology Nanjing210008China nanjing Neurology medical Center Nanjing210008China

Moyamoya disease(MMD)is a chronic occlusive cerebrovascular disease with the development of a network of abnormal *** inflammation is associated with the occurrence and development of ***,the mechanisms underlying the formation of the abnormal vascular network remain ***-eight patients with MMD,26 ischemic stroke patients,and 26 unrelated healthy volunteers were enrolled in this study The data showed that the levels of granulocyte-macrophage colony-stimulating factor(GM-CSF)were higher in MMD patients than in healthy controls(P<0.01),and GM-CSF was mainly from Th1 and Th17 cells in *** found that increased GM-CSF drove monocytes to secrete a series of cytokines associated with angiogenesis,inflammation,and *** summary,our findings demonstrate for the first time the important involvement of GM-CSF in MMD and that GM-CSF is an important factor in the formation of abnormal vascular networks in MMD.

关键词： Moyamoya disease Vascular endothelial cells GM-CSF VEGF