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基因组结构变异研究的前瞻性及临床应用

Science Bulletin 2024年第6期69卷 705-708页

作者：陈仲中 Richard H.Finnell 雷云平王红艳 Obstetrics and Gynecology Hospital State Key Laboratory of Genetic EngineeringInstitute of Reproduction and DevelopmentFudan UniversityShanghai 200011China Shanghai Children’s Hospital School of MedicineShanghai Jiao Tong UniversityShanghai 200062China Center for Precision Environmental Health Department of Molecular and Cellular BiologyBaylor College of MedicineHouston 77030USA Departments of Molecular and Human Genetics and medicine Baylor College of MedicineOne Baylor PlazaHouston 77030USA Shanghai Key Laboratory of Metabolic Remodelling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Children’s Hospital of Fudan University Shanghai 201102China

The challenges and breakthroughs in human genetics can largely depend on the depth of exploring the missing heritability[1]and understanding of genetic variants,which enabled scientists to better elucidate the underlying causes of diseases and apply this knowledge in clinical settings.Human genomes differ from one individual to another in the form of single nucleotide variants(SNVs),small insertions and deletions(indels)(<50 base pairs(bp)),and structural variants(SVs)[2].

关键词： diseases breakthrough insertion

Value of glucose transport protein 1 expression in detecting lymph node metastasis in patients with colorectal cancer

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World Journal of Clinical Cases 2024年第5期12卷 931-941页

作者： Hongsik Kim Song-Yi Choi Tae-Young Heo Kyeong-Rok Kim Jisun Lee Min Young Yoo Taek-Gu Lee Joung-Ho Han Department of Internal medicine Chungbuk National University HospitalCheongju 28644South Korea Department of Pathology Chungnam National University College of MedicineDaejeon 35015South Korea Information and Statistics Chungbuk National UniversityCheongju 28644South Korea Department of Radiology College of MedicineChungbuk National UniversityChungbuk National University HospitalCheongju-si 28644South Korea Department of Nuclear medicine School of MedicineInha UniversityIncheon 22332South Korea Department of Surgery Chungbuk National UniversityCollege of MedicineCheongju-si 28644South Korea Department of Internal Medicen Chungbuk National UniversityCollege of medicineCheongju-si 28644South Korea

BACKGROUND There are limited data on the use of glucose transport protein 1(GLUT-1)expre-ssion as a biomarker for predicting lymph node metastasis in patients with colorectal cancer.GLUT-1 and GLUT-3,hexokinase(HK)-II,and hypoxia-induced factor(HIF)-1 expressions may be useful biomarkers for detecting primary tumors and lymph node metastasis when combined with fluorodeoxyglucose(FDG)uptake on positron emission tomography/computed tomography(PET/CT).AIM To evaluate GLUT-1,GLUT-3,HK-II,and HIF-1 expressions as biomarkers for detecting primary tumors and lymph node metastasis with 18F-FDG-PET/CT.METHODS This retrospective study included 169 patients with colorectal cancer who underwent colectomy and preoperative 18F-FDG-PET/CT at Chungbuk National University Hospital between January 2009 and May 2012.Two tissue cores from the central and peripheral areas of the tumors were obtained and were examined by a dedicated pathologist,and the expressions of GLUT-1,GLUT-3,HK-II,and HIF-1 were determined using immunohisto-chemical staining.We analyzed the correlations among their expressions,various clinicopathological factors,and the maximum standardized uptake value(SUVmax)of PET/CT.RESULTS GLUT-1 was found at the center or periphery of the tumors in 109(64.5%)of the 169 patients.GLUT-1 positivity was significantly correlated with the SUVmax of the primary tumor and lymph nodes,regardless of the biopsy site(tumor center,P<0.001 and P=0.012;tumor periphery,P=0.030 and P=0.010,respectively).GLUT-1 positivity and negativity were associated with higher and lower sensitivities of PET/CT,respectively,for the detection of lymph node metastasis,regardless of the biopsy site.GLUT3,HK-II,and HIF-1 expressions were not significantly correlated with the SUVmax of the primary tumor and lymph nodes.CONCLUSION GLUT-1 expression was significantly correlated with the SUVmax of 18F-FDG-PET/CT for primary tumors and lymph nodes.Clinicians should consider GLUT-1 expression in preoperative endoscopic biopsy in interpreting PET/CT findings.

关键词： 18F-FDG-PET-CT Biomarker Colorectal neoplasms Glucose transporter type 1 Lymph node

Exposure to ephedrine attenuates Th1/Th2 imbalance underlying OVA-induced asthma through airway epithelial cell-derived exo-somal lnc-TRPM2-AS

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Chinese Journal of Natural medicines 2024年第6期22卷 530-540页

作者： HU Yan WANG Mengqing XIE Jing JIAO Luojia DING Yi LUO Yinhe Department of Pediatrics The First Hospital of Hunan University of Chinese MedicineChangsha 410007China Hunan University of Chinese medicine Changsha 410208China Department of Rehabilitation Medical CollegeChangsha Civil Affairs Vocational and Technical CollegeChangsha 410004Hunan ProvinceChina Teaching and Research Office of Chinese and Western Combination Hunan University of Chinese MedicineChangsha 410208China

Although various anti-inflammatory medications,such as ephedrine,are employed to manage cough-variant asthma,their underlying mechanisms are yet to be fully understood.Recent studies suggest that exosomes derived from airway epithelial cells(AECs)contain components like messenger RNAs(mRNAs),micro-RNAs(miRNAs),and long noncoding RNA(lncRNA),which play roles in the occurrence and progression of airway inflammation.This study investigates the influence of AEC-derived exosomes on the efficacy of ephedrine in treating cough-variant asthma.We established a mouse model of asthma and measured airway resist-ance and serum inflammatory cell levels.Real-time polymerase chain reaction(RT-qPCR),Western blotting,and enzyme-linked im-munosorbent assay(ELISA)analyses were used to assess gene and protein expression levels.Exosomes were isolated and character-ized.RNA immunoprecipitation(RIP)and RNA pull-down assays were conducted to examine the interaction between hnRNPA2B1 and lnc-TRPM2-AS1.In the ovalbumin(OVA)-challenged mouse model,ephedrine treatment reduced inflammatory responses,air-way resistance,and Th1/Th2 cell imbalance.Exosomes from OVA-treated AECs showed elevated levels of lnc-TRPM2-AS1,which were diminished following ephedrine treatment.The exosomal lnc-TRPM2-AS1 mediated the Th1/Th2 imbalance in CD4^(+)T cells,with its packaging into exosomes being facilitated by hnRNPA2B1.This study unveils a novel mechanism by which ephedrine ameli-orates OVA-induced CD4^(+)T cell imbalance by suppressing AEC-derived exosomal lnc-TRPM2-AS1.These findings could provide a theoretical framework for using ephedrine in asthma treatment.

关键词： Asthma Ephedrine Exosomal lnc-TRPM2-AS1 Th1/Th2 imbalance HnRNPA2B1 Airway epithelial cells

Prenatal and postnatal factors associated with sudden infant death syndrome:an umbrella review of meta-analyses

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World Journal of Pediatrics 2024年第5期20卷 451-460页

作者： Tae Hyeon Kim Hyeri Lee Selin Woo Hayeon Lee Jaeyu Park Gullume Fond Laurent Boyer Jong Woo Hahn Jiseung Kang Dong Keon Yon Department of medicine Kyung Hee University College of MedicineSeoulSouth Korea Center for Digital Health Medical Science Research InstituteKyung Hee University College of MedicineSeoulSouth Korea Department of Regulatory Science Kyung Hee UniversitySeoulSouth Korea Department of Biomedical Engineering Kyung Hee UniversityYonginSouth Korea CEReSS-Health Service Research and Quality of Life Center Assistance Publique des Hôpitaux de MarseilleAix-Marseille UniversityMarseilleFrance Department of Pediatrics Seoul National University College of MedicineSeoulSouth Korea Department of Pediatrics Seoul National University Bundang HospitalSeongnamSouth Korea Department of Anesthesia Critical Care and Pain MedicineMassachusetts General Hospital14913th StreetRoom 4140CharlestownBostonMAUSA Division of Sleep medicine Harvard Medical SchoolBostonMAUSA Department of Pediatrics Kyung Hee University Medical CenterKyung Hee University College of Medicine23 Kyungheedae-roDongdaemun-guSeoul02447South Korea Department of Precision medicine Kyung Hee University College of MedicineSeoulSouth Korea

Background Comprehensive quantitative evidence on the risk and protective factors for sudden infant death syndrome(SIDS)effects is lacking.We investigated the risk and protective factors related to SIDS.Methods We conducted an umbrella review of meta-analyses of observational and interventional studies assessing SIDS-related factors.PubMed/MEDLINE,Embase,EBSCO,and Google Scholar were searched from inception until January 18,2023.Data extraction,quality assessment,and certainty of evidence were assessed by using A Measurement Tool Assessment Systematic Reviews 2 following PRISMA guidelines.According to observational evidence,credibility was graded and classified by class and quality of evidence(CE;convincing,highly suggestive,suggestive,weak,or not significant).Our study protocol was registered with PROSPERO(CRD42023458696).The risk and protective factors related to SIDS are presented as equivalent odds ratios(eORs).Results We identified eight original meta-analyses,including 152 original articles,covering 12 unique risk and protective factors for SIDS across 21 countries/regions and five continents.Several risk factors,including prenatal drug exposure[eOR=7.84(95%CI=4.81–12.79),CE=highly suggestive],prenatal opioid exposure[9.55(95%CI=4.87–18.72),CE=suggestive],prenatal methadone exposure[9.52(95%CI=3.34–27.10),CE=weak],prenatal cocaine exposure[4.38(95%CI=1.95–9.86),CE=weak],prenatal maternal smoking[2.25(95%CI=1.95–2.60),CE=highly suggestive],postnatal maternal smoking[1.97(95%CI=1.75–2.22),CE=weak],bed sharing[2.89(95%CI=1.81–4.60),CE=weak],and infants found with heads covered by bedclothes after last sleep[11.01(95%CI=5.40–22.45),CE=suggestive],were identified.On the other hand,three protective factors,namely,breastfeeding[0.57(95%CI=0.39–0.83),CE=non-significant],supine sleeping position[0.48(95%CI=0.37–0.63),CE=suggestive],and pacifier use[0.44(95%CI=0.30–0.65),CE=weak],were also identified.Conclusions Based on the evidence,we propose several risk and protective factors for SIDS.This study suggests the need

关键词： Infant Protective factor Risk factor Sudden infant death syndrome Umbrella review

New insights into ATR inhibition in muscle invasive bladder cancer:The role of apolipoprotein B mRNA editing catalytic subunit 3B

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Oncology Research 2024年第6期32卷 1021-1030页

作者： HYUNHO KIM UIJU CHO SOOK HEE HONG HYUNG SOON PARK IN-HO KIM HO JUNG AN BYOUNG YONG SHIM JIN HYOUNG KANG Division of Medical Oncology Department of Internal MedicineSt.Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSuwonKorea Department of Pathology St.Vincent’s HospitalCollege of MedicineThe Catholic University of KoreaSuwonKorea Division of Medical Oncology Department of Internal MedicineSeoul St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoulKorea

Background:Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC),an endogenous mutator,induces DNA damage and activates the ataxia telangiectasia and Rad3-related(ATR)-checkpoint kinase 1(Chk1)pathway.Although cisplatin-based therapy is the mainstay for muscle-invasive bladder cancer(MIBC),it has a poor survival rate.Therefore,this study aimed to evaluate the efficacy of an ATR inhibitor combined with cisplatin in the treatment of APOBEC catalytic subunit 3B(APOBEC3B)expressing MIBC.Methods:Immunohistochemical staining was performed to analyze an association between APOBEC3B and ATR in patients with MIBC.The APOBEC3B expression in MIBC cell lines was assessed using real-time polymerase chain reaction and western blot analysis.Western blot analysis was performed to confirm differences in phosphorylated Chk1(pChk1)expression according to the APOBEC3B expression.Cell viability and apoptosis analyses were performed to examine the anti-tumor activity of ATR inhibitors combined with cisplatin.Results:There was a significant association between APOBEC3B and ATR expression in the tumor tissues obtained from patients with MIBC.Cells with higher APOBEC3B expression showed higher pChk1 expression than cells expressing low APOBEC3B levels.Combination treatment of ATR inhibitor and cisplatin inhibited cell growth in MIBC cells with a higher APOBEC3B expression.Compared to cisplatin single treatment,combination treatment induced more apoptotic cell death in the cells with higher APOBEC3B expression.Conclusion:Our study shows that APOBEC3B’s higher expression status can enhance the sensitivity of MIBC to cisplatin upon ATR inhibition.This result provides new insight into appropriate patient selection for the effective application of ATR inhibitors in MIBC.

关键词： Apolipoprotein B mRNA editing catalytic polypeptide(APOBEC) Ataxia telangiectasia and Rad3-related(ATR) Bladder cancer DNA damage response DNA replication stress

A medium chain fatty acid, 6-hydroxyhexanoic acid (6-HHA), protects against obesity and insulin resistance

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1892-1894页

作者： Sara C.Sebag Meihua Hao Qingwen Qian Chawin Upara Qiong Ding Min Zhu Jeffrey A.Banas Huojun Cao Liu Hong Ling Yang Department of Anatomy and Cell Biology University of Iowa Carver College of MedicineIowa CityIA 52242USA Fraternal Order of Eagles Diabetes Research Center University of Iowa Carver College of MedicineIowa CityIA 52242USA Pappajohn Biomedical Institute University of Iowa Carver College of MedicineIowa CityIA 52242USA Iowa Institute for Oral Health Research University of Iowa College of DentistryIowa CityIA 52242USA

To the Editor,Obesity,one of the most serious health concerns worldwide,exacerbates periodontitis pathogenesis and reduces the effectiveness of treatments1.Conversely,periodontitis-associated inflammation disrupts systemic lipid and glucose homeostasis,the major risk factors for developing obesity-associated pathologies1.Accumulated studies have demonstrated that certain supplemental dietary lipids such as dietary polyunsaturated fatty acids,have beneficial outcomes for diabetic and obese patients.In addition to dietary lipid supply,the oral and gut microbiota produce fatty acids(FAs)which provide the host with essential nutrients and aid in defense against pathogens.Hydroxyhexanoic medium chain FAs(MCFAs;6–12 carbons)are bacterial-derived lipids shown to have anti-inflammatory and insulin sensitization effects in diverse cell types such as hepatocytes2.However,whether and to what extent oral microbiota-produced MCFAs may ameliorate obesity-associated metabolic dysfunction are largely unknown.

关键词： obesity dietary lipids

Etanercept-synthesizing adipose-derived stem cell secretome:A promising therapeutic option for inflammatory bowel disease

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World Journal of Gastrointestinal Surgery 2024年第3期16卷 882-892页

作者： Say-June Kim Ok-Hee Kim Ha-Eun Hong Ji Hyeon Ju Do Sang Lee Department of Surgery Seoul St.Mary’s HospitalCollege of Medicinethe Catholic University of KoreaSeoul 06591South Korea Catholic Central Laboratory of Surgery Institute of Biomedical IndustryCollege of Medicinethe Catholic University of KoreaSeoul 06591South Korea Division of Rheumatology Department of Internal MedicineSeoul St.Mary’s HospitalCollege of MedicineThe Catholic University of KoreaSeoul 06591South Korea

BACKGROUND Inflammatory bowel disease(IBD)is a chronic inflammatory condition of the gastrointestinal tract,with tumor necrosis factor(TNF)-αplaying a key role in its pathogenesis.Etanercept,a decoy receptor for TNF,is used to treat inflammatory conditions.The secretome derived from adipose-derived stem cells(ASCs)has anti-inflammatory effects,making it a promising therapeutic option for IBD.AIM To investigate the anti-inflammatory effects of the secretome obtained from ASCs synthesizing etanercept on colon cells and in a dextran sulfate sodium(DSS)-induced IBD mouse model.METHODS ASCs were transfected with etanercept-encoding mini-circle plasmids to create etanercept-producing cells.The secretory material from these cells was then tested for anti-inflammatory effects both in vitro and in a DSS-induced IBD mouse model.RESULTS This study revealed promising results indicating that the group treated with the secretome derived from etanercept-synthesizing ASCs[Etanercept-Secretome(Et-Sec)group]had significantly lower expression levels of inflammatory mediators,such as interleukin-6,Monocyte Chemoattractant Protein-1,and TNF-α,when compared to the control secretome(Ct-Sec).Moreover,the Et-Sec group exhibited a marked therapeutic effect in terms of preserving the architecture of intestinal tissue compared to the Ct-Sec.CONCLUSION These results suggest that the secretome derived from ASCs that synthesize etanercept has potential as a therapeutic agent for the treatment of IBD,potentially enhancing treatment efficacy by merging the anti-inflam-matory qualities of the ASC secretome with etanercept's targeted approach to better address the multifaceted pathophysiology of IBD.

关键词： Adipose-derived stem cells Etanercept Inflammatory bowel disease Secretome Tumor necrosis factor-α

Clinical diagnostic advances in intestinal anastomotic techniques:Hand suturing,stapling,and compression devices

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World Journal of Gastrointestinal Surgery 2024年第5期16卷 1231-1234页

作者： Ah Young Lee Joo Young Cho Division of Gastroenterology Department of Internal MedicineCha Gangnam Medical CenterCha University College of MedicineSeoul 06135South Korea

The development of intestinal anastomosis techniques,including hand suturing,stapling,and compression anastomoses,has been a significant advancement in surgical practice.These methods aim to prevent leakage and minimize tissue fibrosis,which can lead to stricture formation.The healing process involves various phases:hemostasis and inflammation,proliferation,and remodeling.Mechanical staplers and sutures can cause inflammation and fibrosis due to the release of profibrotic chemokines.Compression anastomosis devices,including those made of nickel-titanium alloy,offer a minimally invasive option for various surgical challenges and have shown safety and efficacy.However,despite advancements,anastomotic techniques are evaluated based on leakage risk,with complications being a primary concern.Newer devices like Magnamosis use magnetic rings for compression anastomosis,demonstrating greater strength and patency compared to stapling.Magnetic technology is also being explored for other medical treatments.While there are promising results,particularly in animal models,the realworld application in humans is limited,and further research is needed to assess their safety and practicality.

关键词： Anastomoses Diagnostic advances,Anastomotic techniques Technique Intestine

Fu-Zheng-Yi-Liu Formula inhibits the stem cells and metastasis of prostate cancer via tumor-associated macrophages/C-C motif chemokine ligand 5 pathway in tumor microenvironment

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Chinese Journal of Natural medicines 2024年第6期22卷 501-514页

作者： CHEN Chiwei HUANG Renlun WANG Neng ZHENG Yifeng ZHOU Jianfu YANG Bowen WANG Xuan ZHANG Juping PAN Bo CHEN Zhiqiang WANG Shengqi WANG Zhiyu XIANG Songtao The Research Center of Integrative Cancer medicine Discipline of Integrated Chinese and Western Medicinethe Second Clinical College of Guangzhou University of Chinese MedicineGuangzhou 510000China The First Clinical college of Guangzhou University of Chinese medicine Guangzhou 510000China Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese medicine Syndrome Guangdong Provincial Academy of Chinese Medical SciencesGuangdong Provincial Hospital of Chinese MedicineGuangzhou 510000China Guangdong-Hong Kong-Macao Joint Lab on Chinese medicine and Immune Disease Research Guangzhou University of Chinese MedicineGuangzhou 510000China The Research Center for Integrative medicine School of Basic Medical SciencesGuangzhou University of Chinese MedicineGuangzhou 510000China State Key Laboratory of Dampness Syndrome of Chinese medicine The Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510000China

Prostate cancer(PCa)is the second most common malignancy among men globally.The Fu-Zheng-Yi-Liu(FZYL)Formula has been widely utilized in the treatment of PCa.This study investigates whether the FZYL Formula can inhibit PCa by tar-geting the TAMs/CCL5 pathway.We conducted in vitro co-cultures and in vivo co-injections of PCa cells and TAMs to mimic their in-teraction.Results showed that the FZYL Formula significantly reduced the proliferation,colony formation,subpopulations of PCSCs,and sphere-formation efficacy of PCa cells,even in the presence of TAM co-culture.Additionally,the Formula markedly decreased the migration,invasion,and epithelial-mesenchymal transition(EMT)of PCa cells induced by TAMs.The FZYL Formula also reversed M2 phenotype polarization in TAMs and dose-dependently reduced their CCL5 expression and secretion,with minimal cytotoxicity observed.Mechanistic studies confirmed that the TAMs/CCL5 axis is a critical target of the FZYL Formula,as the addition of exogen-ous CCL5 partially reversed the formula’s inhibitory effects on PCSCs self-renewal in the co-culture system.Importantly,the Formula also significantly inhibited the growth of PCa xenografts,bone metastasis,and PCSCs activity in vivo by targeting the TAMs/CCL5 pathway.Overall,this study not only elucidates the immunomodulatory mechanism of the FZYL Formula in PCa therapy but also highlights the TAMs/CCL5 axis as a promising therapeutic target.

关键词： Traditional Chinese medicine Tumor-associated macrophages Prostate cancer stem cells CCL5 Tumor microenvironment