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

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

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Semaphorin 3C (Sema3C) reshapes stromal microenvironment to promote hepatocellular carcinoma progression

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3429-3448页

作者： Hao Peng Meng Yang Kun Feng Qingpeng Lv Yewei Zhang medical School Southeast UniversityNanjing 210009China Department of Ultrasound State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalChinese Academy of MedicalSciencesPeking Union Medical CollegeBeijing 100730China Hepatopancreatobiliary Center The Second Affiliated Hospital of Nanjing Medical UniversityNanjing 210009China

More than 90% of hepatocellular carcinoma(HCC)cases develop in the presence of fibrosis or cirrhosis,making the tumor microenvironment(TME)of HCC distinctive due to the intricate interplay between cancer-associated fibroblasts(CAFs)and cancer stem cells(CSCs),which collectively regulate HCC ***,the mechanisms through which CSCs orchestrate the dynamics of the tumor stroma during HCC development remain *** study unveils a significant upregulation of Sema3C in fibrotic liver,HCC tissues,peripheral blood of HCC patients,as well as sorafenib-resistant tissues and cells,with its overexpression correlating with the acquisition of stemness properties in *** further identify NRP1 and ITGB1 as pivotal functional receptors of Sema3C,activating downstream AKT/Gli1/c-Myc signaling pathways to bolster HCC self-renewal and tumor ***,HCCcells-derived Sema3Cfacilitated extracellular matrix(ECM)contraction and collagen deposition in vivo,while also promoting the proliferation and activation of hepatic stellate cells(HSCs).Mechanistically,Sema3C interacted with NRP1 and ITGB1 in HSCs,activating downstream NF-kB signaling,thereby stimulating the release of IL-6 and upregulating HMGCR expression,consequently enhancing cholesterol synthesis in ***,CAF-secreted TGF-β1 activates AP1 signaling to augment Sema3C expression in HCC cells,establishing a positive feedback loop that accelerates HCC ***,blockade of Sema3C effectively inhibits tumor growth and sensitizes HCC cells to sorafenib in *** sum,our findings spotlight Sema3C as a novel biomarker facilitating the crosstalk between CsCs and stroma during hepatocarcinogenesis,thereby offering a promising avenue for enhancing treatment efficacy and overcoming drug resistance in HCC.

关键词： Sema hepatocellular thereby

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Recommendations for articles and reviews in colorectal cancerrelated research at the year-end of 2023

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World Journal of Gastroenterology 2024年第30期30卷 3548-3553页

作者： Wen-Yu Luan Hao Lin Yan-Dong Miao Department of cancer Center The Yantai Affiliated Hospital of Binzhou Medical UniversityThe Second Medical College of Binzhou Medical UniversityYantai 264100Shandong ProvinceChina

As peer reviewers of the World Journal of Gastroenterology,our weekly routine involves immersing ourselves in the newly published issue,particularly focusing on the realm of colorectal cancer(CRC)*** diligently sift through various contributions,ranging from comprehensive reviews to original articles and other scholarly *** meticulous examination,we discern the most notable papers,delving into each with careful scrutiny to distill their merits and ***,this undertaking demands considerable time and ***,it stands as an indispensable pursuit,affording us a profound comprehension of the latest breakthroughs in CRC ***,these meticulously curated selections furnish readers with invaluable resources,serving as enduring references for the nuanced exploration of this dynamic field.

关键词： Colorectal cancer Molecular mechanism Genetic marker Application of new technologies Diagnosis Treatment

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Liposomalα-cyperone targeting bone resorption surfaces suppresses osteoclast differentiation and osteoporosis progression via the PI3K/Akt axis

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Nano Research 2024年第4期17卷 2949-2959页

作者： Lin Yang Xueying An Wang Gong Wenshu Wu Bin Liu Xiaoyan Shao Yansi Xian Rui Peng Baosheng Guo Qing Jiang Division of Sports Medicine and Adult Reconstructive Surgery Department of Orthopedic SurgeryNanjing Drum Tower Hospital Clinical College of Nanjing Medical University321 Zhongshan RoadNanjing 210008China Branch of National Clinical Research Center for Orthopedics Sports Medicine and RehabilitationNanjing 210008China State Key Laboratory of Pharmaceutical Biotechnology Medical SchoolNanjing University&Division of Sports Medicine and Adult Reconstructive SurgeryDepartment of Orthopedic SurgeryNanjing Drum Tower HospitalThe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China

Osteoporosis is a metabolic dysregulation of bone that occurs mainly in postmenopausal women,and the hyperfunction of osteoclasts is the primary contributor to postmenopausal ***,the development of effective therapeutic drugs and precise delivery systems remains a challenge in the field of anti-absorption ***,we reported theα-cyperone(α-CYP)for anti-osteoporosis and developed a liposome-based nano-drug delivery system ofα-CYP,that specifically targets the bone resorption ***,we found that theα-CYP,one of the major sesquiterpenes of Cyperus rotundus L.,attenuated the progression of osteoporosis in ovariectomized(OVX)mice and down-regulated the expression of phosphorylated proteins of phosphoinositide 3-kinase(PI3K)and protein kinase B(Akt),causing down-regulation of osteoclast-related genes/proteins and curbing osteoclast ***,α-CYP reversed the activation of osteoclastic differentiation and enhanced osteoporosis-related proteins expression caused by PI3K/Akt agonist(YS-49).More importantly,we adopted the osteoclastic resorption surface targeting peptide Asp8 and constructed the liposome(lipαC@Asp8)to deliverα-CYP to osteoclasts and confirmed its anti-osteoporosis effect and enhanced osteoclast inhibition by blocking PI3K/Akt *** conclusion,this study demonstrated thatα-CYP inhibits osteoclast differentiation and osteoporosis development by silencing PI3K/Akt pathway,and the liposome targeting delivery systems loaded withα-CYP might provide a novel and effective strategy to treat osteoporosis.

关键词： osteoporosis α-cyperone osteoclast phosphoinositide 3-kinase/protein kinase B(PI3K/Akt) liposome

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Risk factors associated with intraoperative persistent hypotension in pancreaticoduodenectomy

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World Journal of Gastrointestinal Surgery 2024年第6期16卷 1582-1591页

作者： Xing-Jun Wang Xi-Chen Xuan Zhao-Chu Sun Shi Shen Fan Yu Na-Na Li Xue-Chun Chu Hui Yin You-Li Hu Department of Anesthesia and Perioperative Medicine The First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029Jiangsu ProvinceChina

BACKGROUND Intraoperative persistent hypotension(IPH)during pancreaticoduodenectomy(PD)is linked to adverse postoperative outcomes,yet its risk factors remain *** To clarify the risk factors associated with IPH during PD,ensuring patient safety in the perioperative *** A retrospective analysis of patient records from January 2018 to December 2022 at the First affiliated hospital of nanjing medical university identified factors associated with IPH in *** factors included age,gender,body mass index,American Society of Anesthesiologists classification,comorbidities,medication history,operation duration,fluid balance,blood loss,urine output,and blood gas *** was defined as sustained mean arterial pressure30 min despite additional deoxyepinephrine and fluid *** Among 1596 PD patients,661(41.42%)experienced *** logistic regression identified key risk factors:increased age[odds ratio(OR):1.20 per decade,95%confidence interval(CI):1.08-1.33](P<0.001),longer surgery duration(OR:1.15 per additional hour,95%CI:1.05-1.26)(P<0.01),and greater blood loss(OR:1.18 per 250-mL increment,95%CI:1.06-1.32)(P<0.01).A novel finding was the association of arterial blood Ca^(2+)<1.05 mmol/L with IPH(OR:2.03,95%CI:1.65-2.50)(P<0.001).CONCLUSION IPH during PD is independently associated with older age,prolonged surgery,increased blood loss,and lower plasma Ca^(2+).

关键词： Risk factors Pancreaticoduodenectomy Perioperative period Intraoperative persistent hypotension Retrospective cohort study

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LSM6 promotes cell proliferation and migration regulated by HMGB1 in laryngeal squamous cell carcinoma

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Engineered Regeneration 2024年第2期5卷 247-254页

作者： Dengbin Ma Jiayi Li Hui Li Yao Tang Xia Gao Hong Chen Xiaoyun Qian Xiaohui Shen Department of Otolaryngology Head and Neck Surgery Research Institute of OtolaryngologyNanjing Drum Tower HospitalJiangsu Provincial Key Medical DisciplineAffiliated Hospital of medical SchoolNanjing UniversityNanjing210008China Department of Otorhinolaryngology Minda Hospital of Hubei Minzu UniversityEnshi445000China nanjing Drum Tower hospital Clinical College of nanjing medical university 321 Zhongshan RoadNanjing210008China

Elevated levels of high mobility group protein B1(HMGB1)play a significant role in the pathogenesis of many diseases,but is particularly important for the formation of malignant ***,the function of HMGB1 and the underlying mechanism of laryngeal squamous cell carcinoma(LSCC)remain incompletely understood,causing *** we found immunohistochemistry from 97 LSCC tissues showed HMGB1 was upreg-ulated,which was associated with poor ***1 knockdown could significantly inhibit wound closure and colony *** full-genome gene expression microarray was performed to investigate the *** knockdown of HMGB1 by siRNA,among the expressed differential genes,10 genes were ran-domly selected for ***,shRNA lentivirus targeting these genes were constructed to explore their role in LSCC by cell proliferation ***6 downregulation was dramatically promoted by HMGB1 knockdown,resulting in higher expression in LSCC ***,downregulation of LSM6 could significantly suppress cell proliferation,migration and colony *** study indicated that HMGB1 promoted LSCC cell malig-nant phenotypes through regulation of *** anticipate that HMGB1-LSM6 could be a putative therapeutic target for LSCC.

关键词： HMGB1 LSM6 Laryngeal squamous cell carcinoma Cell proliferation Migration

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Establishment and evaluation of an improved rat model of open abdomen

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Animal Models and Experimental Medicine 2024年第4期7卷 562-569页

作者： Ye Liu Sicheng Li Jinjian Huang Ze Li Kang Chen Guiwen Qu Xiuwen Wu Jianan Ren School of Medicine Southeast UniversityNanjingChina Research Institute of General Surgery Affiliated Jinling HospitalMedical School of Nanjing UniversityNanjingChina

Introduction:This study aimed to establish an animal model of open abdomen(OA)through temporary abdominal closure via different ***:Adult male Sprague-Dawley rats were randomly divided into three groups:group A(OA with polypropylene mesh alone);group B(OA with polypro-pylene mesh combined with a patch);and group C(OA with polypropylene mesh and a sutured patch).Vital signs,pathophysiological changes,and survival rates were closely monitored in the rats for 7 days after *** X-rays and histopathological examinations were performed to assess abdominal organ changes and wound ***:The results showed no significant difference in mortality rates among the three groups(p>0.05).However,rats in group B exhibited superior overall condi-tion,cleaner wounds,and a higher rate of wound healing compared to the other groups(p<0.05).Abdominal X-rays indicated that varying degrees of distal intestinal obstruction in all *** examinations revealed fibrous hyperpla-sia,inflammatory cell infiltration,neovascularization,and collagen deposition in all *** B demonstrated enhanced granulation tissue generation,neovasculari-zation,and collagen deposition compared to the other groups(p<0.05).Conclusions:Polypropylene mesh combined with patches is the most suitable method for establishing an animal model of *** model successfully replicated the patho-logical and physiological changes in postoperative patients with OA,specifically the progress of abdominal skin wound *** provides a practical and reliable animal model for OA research.

关键词： animal models open abdomen patch polypropylene mesh

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Association between glucose-lowering drugs and circulating insulin antibodies induced by insulin therapy in patients with type 2 diabetes

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World Journal of Diabetes 2024年第7期15卷 1489-1498页

作者： Peng Zhang Qing Jiang Bo Ding Reng-Na Yan Yun Hu Jian-Hua Ma Department of Endocrinology Nanjing First HospitalNanjing Medical UniversityNanjing 210000Jiangsu ProvinceChina Department of Endocrinology The Affiliated Wuxi People's Hospital of Nanjing Medical UniversityWuxi Medical CenterWuxi 214000Jiangsu ProvinceChina

BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin *** To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabetes mellitus(T2DM).METHODS This cross-sectional,retrospective study included 1863 patients with T2DM who were receiving exogenous insulin *** patients received stable antidiabetic therapy in the last 3 months and IA levels were measured using an iodine-125 *** A total of 1863 patients were *** were 902(48.4%)patients who had positive IAs(IA level>5%),with a mean IA level of 11.06%(10.39%-11.72%).IA levels were positively correlated with high fasting blood glucose(odds ratio=1.069,P<0.001).The proportion of positive IAs was lowest in patients using glargine only(31.9%)and highest in patients using human insulin only(70.3%),P<*** IA levels in patients using sulfonylureas/glinides(8.3%),metformin(9.6%),and dipeptidyl peptidase-4 inhibitors(8.2%)were all lower than in patients without these drugs(all P<0.05).CONCLUSION Nearly half of patients on insulin therapy have positive IA antibodies,and IA antibody levels are associated with blood glucose *** glargine and a combination of oral glucose-lowering drugs were correlated with lower IA levels.

关键词： Insulin antibodies Insulin therapy Glucose-lowering drugs Glargine Type 2 diabetes

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Sintilimab(anti-PD-1 antibody)plus chidamide(histone deacetylase inhibitor)in relapsed or refractory extranodal natural killer T-cell lymphoma(SCENT):a phase Ⅰb/Ⅱ study

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2765-2773页

作者： Yan Gao Haixia He Xueping Li Liling Zhang Wei Xu Ru Feng Wenyu Li Yin Xiao Xinxiu Liu Yu Chen Xiaoxiao Wang Bing Bai Huijing Wu Qingqing Cai Zhiming Li Jibin Li Suxia Lin Yanxia He Liqin Ping Cheng Huang Jiaying Mao Xiujin Chen Baitian Zhao Huiqiang Huang State Key Laboratory of Oncology in South China&Collaborative Innovation Center of cancer Medicine Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhouChina Department of medical Oncology Sun Yat-sen University Cancer CenterGuangzhouChina Department of Radiation Oncology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouChina Department of Hematology Sun Yat-sen University Cancer CenterGuangzhouChina cancer Center Union Hospital affiliated to Tongji Medical College of Huazhong University of Science and TechnologyWuhanChina Department of Hematology The First Affiliated Hospital of Nanjing Medical UniversityJiangsu Province HospitalNanjingChina Department of Hematology Nanfang HospitalSouthern Medical UniversityGuangzhouChina Department of Lymphoma Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhouChina Department of pathology Guangdong General HospitalGuangdong Academy of Medical SciencesGuangzhouChina Department of medical Oncology Hubei Cancer CenterWuhanChina Department of Clinical Research Sun Yat-sen University Cancer CenterGuanzhouChina Department of Pathology Sun Yat-sen University Cancer CenterGuangzhouChina

Anti-PD-1 antibodies are a favorable treatment for relapsed or refractory extranodal natural killer T cell lymphoma(RR-ENKTL),however,the complete response(CR)rate and the duration of response(DOR)need to be *** phase 1b/2 study investigated the safety and efficacy of sintilimab,a fully human anti-PD-1 antibody,plus chidamide,an oral subtype-selective histone deacetylase inhibitor in 38 patients with *** objective response rate(ORR)of combination treatment was 80%.Patients received escalating doses of chidamide,administered concomitantly with fixed-dose sintilimab in 21-days cycles up to 12 *** dose-limiting events were observed,RP2D of chidamide was 30 mg twice a ***-nine patients were enrolled in phase *** the intention-to-treat population(n=37),overall response rate was 59.5% with a complete remission rate of 48.6%.The median DOR,progression-free survival(PFS),and overall survival(OS)were 25.3,23.2,and 32.9 months,*** most common grade 3 or higher treatment-emergent adverse events(AEs)were neutropenia(28.9%)and thrombocytopenia(10.5%),immune-related AEs were reported in 18(47.3%)*** biomarker assessment suggested that a combination of dynamic plasma ctDNA and EBV-DNA played a vital prognostic ***3 mutation shows an unfavorable *** outcome of anticipate ORR was not achieved,sintilimab plus chidamide was shown to have a manageable safety profile and yielded encouraging CR rate and DOR in RR-ENKTL for the first *** is a promising therapeutic option for this population.

关键词： killer lymphoma doses

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How mesenchymal stem cells transform into adipocytes:Overview of the current understanding of adipogenic differentiation

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World Journal of Stem Cells 2024年第3期16卷 245-256页

作者： Shan-Shan Liu Xiang Fang Xin Wen Ji-Shan Liu Miribangvl Alip Tian Sun Yuan-Yuan Wang Hong-Wei Chen Department of Reumatology and Immunology Nanjing Drum Tower HospitalThe Affiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008Jiangsu ProvinceChina Department of Emergency Nanjing Drum Tower HospitalThe Affiliated Hospital of Medical SchoolNanjing UniversityNanjing 210008Jiangsu ProvinceChina Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education School of Biological Science and Medical EngineeringBeihang UniversityBeijing 100191China Anhui Key Laboratory of Infection and Immunity Bengbu Medical CollegeBengbu 233000Anhui ProvinceChina

Mesenchymal stem cells(MSCs)are stem/progenitor cells capable of self-renewal and differentiation into osteoblasts,chondrocytes and *** transformation of multipotent MSCs to adipocytes mainly involves two subsequent steps from MSCs to preadipocytes and further preadipocytes into adipocytes,in which the process MSCs are precisely controlled to commit to the adipogenic lineage and then mature into *** studies have shown that the master transcription factors C/enhancer-binding protein alpha and peroxisome proliferation activator receptor gamma play vital roles in ***,the mechanism underlying the adipogenic differentiation of MSCs is not fully ***,the current knowledge of adipogenic differentiation in MSCs is reviewed,focusing on signaling pathways,noncoding RNAs and epigenetic effects on DNA methylation and acetylation during MSC ***,the relationship between maladipogenic differentiation and diseases is briefly *** hope that this review can broaden and deepen our understanding of how MSCs turn into adipocytes.

关键词： Mesenchymal stem cell Adipogenic differentiation Signaling pathway Noncoding RNA Epigenetic regulation

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