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Identification and validation of novel prognostic fatty acid metabolic gene signatures in colon adenocarcinoma through systematic approaches

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Oncology Research 2024年第2期32卷 297-308页

作者： HENG ZHANG WENJING CHENG HAIBO ZHAO WEIDONG CHEN QIUJIE ZHANG qing-qing yu Department of Laboratory Shandong Daizhuang HospitalJining272051China Jining No.1 People’s Hospital Shandong First Medical UniversityJining272000China

Colorectal cancer(CRC)belongs to the class of significantly malignant tumors found in humans.Recently,dysregulated fatty acid metabolism(FAM)has been a topic of attention due to its modulation in cancer,specifically CRC.However,the regulatory FAM pathways in CRC require comprehensive elucidation.Methods:The clinical and gene expression data of 175 fatty acid metabolic genes(FAMGs)linked with colon adenocarcinoma(COAD)and normal cornerstone genes were gathered through The Cancer Genome Atlas(TCGA)-COAD corroborating with the Molecular Signature Database v7.2(MSigDB).Initially,crucial prognostic genes were selected by uni-and multi-variate Cox proportional regression analyses;then,depending upon these identified signature genes and clinical variables,a nomogram was generated.Lastly,to assess tumor immune characteristics,concomitant evaluation of tumor immune evasion/risk scoring were elucidated.Results:A 8-gene signature,including ACBD4,ACOX1,CD36,CPT2,ELOVL3,ELOVL6,ENO3,and SUCLG2,was generated,and depending upon this,CRC patients were categorized within high-risk(H-R)and low-risk(L-R)cohorts.Furthermore,risk and age-based nomograms indicated moderate discrimination and good calibration.The data confirmed that the 8-gene model efficiently predicted CRC patients’prognosis.Moreover,according to the conjoint analysis of tumor immune evasion and the risk scorings,the H-R cohort had an immunosuppressive tumor microenvironment,which caused a substandard prognosis.Conclusion:This investigation established a FAMGs-based prognostic model with substantially high predictive value,providing the possibility for improved individualized treatment for CRC individuals.

关键词： Fatty acid metabolism Colorectal cancer Gene signatures Machine learning

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Protein neddylation and its role in health and diseases

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1869-1904页

作者： Shizhen Zhang qing yu Zhijian Li Yongchao Zhao Yi Sun Department of Breast Surgery the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310029China Cancer Institute(Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education)the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310029China Institute of Translational Medicine Zhejiang University School of MedicineHangzhou 310029China Department of Thyroid Surgery Zhejiang Cancer HospitalInstitute of Basic Medicine and Cancer(IBMC)Chinese Academy of SciencesHangzhou 310022China Key Laboratory of Head&Neck Cancer Translational Research of Zhejiang Province Hangzhou 310022China Department of Hepatobiliary and Pancreatic Surgery Zhejiang University School of MedicineHangzhou 310029China Zhejiang Provincial Key Laboratory of Pancreatic Disease The First Affiliated HospitalZhejiang University School of MedicineHangzhou 310029China Zhejiang University Cancer Center Hangzhou 310029China Leading Innovative and Entrepreneur Team Introduction Program of Zhejiang Hangzhou 310024China Research Center for Life Science and Human Health Binjiang Institute of Zhejiang UniversityHangzhou 310053China

NEDD8(Neural precursor cell expressed developmentally downregulated protein 8)is an ubiquitin-like protein that is covalently attached to a lysine residue of a protein substrate through a process known as neddylation,catalyzed by the enzyme cascade,namely NEDD8 activating enzyme(E1),NEDD8 conjugating enzyme(E2),and NEDD8 ligase(E3).The substrates of neddylation are categorized into cullins and non-cullin proteins.Neddylation of cullins activates CRLs(cullin RING ligases),the largest family of E3 ligases,whereas neddylation of non-cullin substrates alters their stability and activity,as well as subcellular localization.Significantly,the neddylation pathway and/or many neddylation substrates are abnormally activated or over-expressed in various human diseases,such as metabolic disorders,liver dysfunction,neurodegenerative disorders,and cancers,among others.Thus,targeting neddylation becomes an attractive strategy for the treatment of these diseases.In this review,we first provide a general introduction on the neddylation cascade,its biochemical process and regulation,and the crystal structures of neddylation enzymes in complex with cullin substrates;then discuss how neddylation governs various key biological processes via the modification of cullins and non-cullin substrates.We further review the literature data on dysregulated neddylation in several human diseases,particularly cancer,followed by an outline of current efforts in the discovery of small molecule inhibitors of neddylation as a promising therapeutic approach.Finally,few perspectives were proposed for extensive future investigations.

关键词： NEDD8 attached attractive

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Factors and Their Impact on Treatment Effect of Acupuncture in Different Outcomes:A Meta-Regression of Acupuncture Randomized Controlled Trials

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Chinese Journal of Integrative Medicine 2024年第3期30卷 260-266页

作者： XIU Wen-cui GANG Wei-juan ZHOU Qi SHI Lan-jun HU Xiang-yu MING Tian-yu LUO Zhen ZHANG yu-qing JING Xiang-hong Institute of Acupuncture and Moxibustion China Academy of Chinese Medical SciencesBeijing100700China China Center for Evidence-Based Traditional Chinese Medicine China Academy of Chinese Medical SciencesBeijing100700China Department of Health Research Methods Evidenceand ImpactMcMaster UniversityHamiltonOntarioL8S 4L8Canada Center for Evidence-Based Integrative Medicine-Clarity Collaboration Guang’anmen HospitalChina Academy of Chinese Medical SciencesBeijing100053China

Background:The effects of acupuncture have varied in different randomized controlled trials(RCTs),and there are many factors that influence treatment effect of acupuncture in different outcomes,with conflicting results.Objective:To identify factors and their impact on the treatment effect of acupuncture in different outcomes.Methods:Acupuncture RCTs were searched from 7 databases including Medline(Pub Med),Embase,Cochrane Central Register of Controlled Trials,China National Knowledge Infrastructure,Wanfang Database,VIP Database,and China Biology Medicine disc between January 1st,2015 and December 31st,2019.Eligible studies must compare acupuncture to no acupuncture,sham acupuncture,or waiting lists,and report at least 1patient-important outcome.A multi-level meta-regression was conducted using a 3-level robust mixed model and univariate analyses were performed for all independent variables,even those excluded from the multivariable model due to collinearities.We used thresholds of 0.2 and 0.4 for the difference of standardized mean differences(SMDs),categorising them as small(0.4) effects.Results:The pain construct analysis involved 211 effect estimates from 153 studies and 14 independent variables.High-frequency acupuncture treatment sessions produced larger effects compared to low-frequency sessions [large magnitude,the difference of adjusted SMDs 0.46,95% confidence interval(CI) 0.07 to 0.84;P=0.02].The non-pain symptoms construct analysis comprised 323 effect estimates from 231 studies and 15 independent variables.Penetrating acupuncture showed moderately larger effects when compared to non-penetrating acupuncture(0.30,95% CI 0.06 to 0.53;P=0.01).The function construct analysis included 495 effect estimates from 274 studies and 14 independent variables.Penetrating acupuncture and the flexible acupuncture regimen showed moderately larger effects,compared to non-penetrating acupuncture and fixed regimen,respectively(0.40,95% CI 0 to 0.80;P=0.05;0.29,95% CI 0.06 to 0.53;P=0.01).

关键词： acupuncture randomized controlled trial patient-important outcome meta-regression

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Chemotherapy combined with bevacizumab for small cell lung cancer with brain metastases:A case report

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World Journal of Clinical Cases 2024年第2期12卷 405-411页

作者： Hong-yu Yang yu-qing Xia yu-Jia Hou Peng Xue Shi-Jie Zhu Dian-Rong Lu Department of Oncology Wangjing HospitalChina Academy of Chinese Medical SciencesBeijing 100102China Department of Oncology Tianjin University of Chinese MedicineTianjin 300000China Department of Electrothermal Acupuncture Wangjing HospitalChina Academy of Chinese Medical SciencesBeijing 100102China Department of Acupuncture and Moxibustion Sihui Hospital of Traditional Chinese MedicineBeijing 100102China

BACKGROUND Small cell lung cancer(SCLC)is a common and aggressive subtype of lung cancer.It is characterized by rapid growth and a high mortality rate.Approximately 10%of patients with SCLC present with brain metastases at the time of diagnosis,which is associated with a median survival of 5 mo.This study aimed to summarize the effect of bevacizumab on the progression-free survival(PFS)and overall survival of patients with brain metastasis of SCLC.CASE SUMMARY A 62-year-old man was referred to our hospital in February 2023 because of dizziness and numbness of the right lower extremity without headache or fever for more than four weeks.The patient was diagnosed with limited-stage SCLC.He received 8 cycles of chemotherapy combined with maintenance bevacizumab therapy and achieved a PFS of over 7 mo.CONCLUSION The combination of bevacizumab and irinotecan effectively alleviated brain metastasis in SCLC and prolonged PFS.

关键词： Small cell lung cancer Bevacizumab Brain metastasis Antineoplastic agents Target therapies Immunotherapy Radiotherapy Case report

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Heterochronous multiple primary prostate cancer and lymphoma:A case report

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World Journal of Clinical Cases 2024年第7期12卷 1333-1338页

作者： Jin-Long Liang yu-qing Bu Li-Li Peng Hong-Zhen Zhang Department of Oncology Hebei General HospitalShijiazhuang 050051Hebei ProvinceChina

BACKGROUND Multiple primary malignant tumors(MPMTs)are rare type of cancer,especially when solid tumors are the first and lymphoma is the second primary malignancy.We report a patient with heterochronous MPMTs consisting of prostate cancer and rectal diffuse large B-cell lymphoma(DLBCL).CASE SUMMARY We report a 77-year-old male patient diagnosed with prostate cancer who was treated with radiation therapy and one year of endocrine therapy with bicalutamide(50 mg per day)and an extended-release implant of goserelin(1/28 d).Seven years later,rectal DLBCL with lung metastases was found.CONCLUSION Although rare,the possibility of prostate cancer combined with a double primary cancer of DLBCL can provide a deeper understanding.

关键词： Multiple primary malignant tumors Radiation therapy Diffuse large B-cell lymphoma Prostate cancer Non-Hodgkin lymphoma Case report

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Effect of Sc on Al_(3)Fe phase and mechanical properties of as-cast AA5052 aluminum alloy

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China Foundry 2024年第3期21卷 257-264页

作者： Yang Li qing yu Feng-feng Chen Jia-wen He Hong-mei Yang Meng-nie Li Faculty of Materials Science and Engineering Kunming University of Science and TechnologyKunming 650093China

The AA5052 aluminum alloy is widely used in automobile and aerospace manufacturing,and with the development of light-weight alloys,it is required that these materials exhibit better mechanical properties.Previous studies have demonstrated that the addition of Sc to aluminum alloys can improve both the microstructure and properties of the alloys.In this study,the effect of Sc on the Fe-rich phase and properties of the AA5052 aluminum alloy was studied by adding 0%,0.05%,0.2%,and 0.3%Sc.The results show that with the increase of Sc,the coarse needle-like Fe-rich phase gradually transforms into Chinese-script and then nearly spherical particles,reduce the size of Fe-rich phase,and refine the grain with increase of high angle grain boundaries(HAGBs).These microstructure changes enhance the strength of the AA5052 alloy through Sc addition.The ductility of the alloy is obviously improved because the addition of a lower amount of Sc changes the morphology of Fe-rich phase from needle-like into a Chinese-script,and it is subsequently reduced as a result of significant increase in HAGBs with increasing Sc content.

关键词： AA5052 aluminum alloy Al3Fe phase mechanical properties grain boundary

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Chalcone derivatives as novel,potent and selective inhibitors against human Notum:Structure–activity relationships and biological evaluations

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Chinese Chemical Letters 2024年第3期35卷 321-325页

作者： Jin-Hui Shi Bei Zhao Li-Lin Song yu-qing Song Meng-Ru Sun Tian Tian Hong-yu Chen yun-qing Song Jian-Ming Sun Guang-Bo Ge Shanghai Frontiers Science Center of TCM Chemical Biology Institute of Interdisciplinary Integrative Medicine Research Shanghai University of Traditional Chinese MedicineShanghai 201203China Dalian Engineering Research Center for Carbohydrate Agricultural Preparations Liaoning Provincial Key Laboratory of CarbohydratesDalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine Shanghai 200137China

Human Notum(hNotum)inhibitors could be used for treating Wnt signalling-associated diseases including colorectal cancer.Herein,two series of chalcone derivatives were designed and synthesized aiming to find selective and potent hNotum inhibitors.Structure–activity relationship(SAR)studies showed that 2-methoxyl and 5-bromine substitutions on A-ring significantly enhanced anti-hNotum effect,while 4’-ethoxyl and 3’-alkyl substitutions on B-ring were beneficial for hNotum inhibition.Among all tested chalcones,B11 displayed the most potent anti-Notum effect(IC_(50)=3.6 nmol/L),good selectivity,excellent chemical stability and suitable metabolic stability.Further investigations showed that B11 acted as a competitive inhibitor of hNotum,while this agent(5μmol/L)significantly weaken the migration abilities of colorectal cancer cells.Collectively,this study deciphers the SARs of chalcones as hNotum inhibitors and reports a novel and potent hNotum inhibitor with the anti-migration effect on colorectal cancer cells,which offers a promising lead compound to develop novel anti-cancer agents.

关键词： Human notum(hNotum) Chalcone Computer-assisted drug discovery Structure–activity relationship(SAR) Anti-colorectal cancer agent

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Biomimetic microchannel network with functional endothelium formed by sacrificial electrospun fibers inside 3D gelatin methacryloyl(GelMA)hydrogel models

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2024年第1期25卷 79-96页

作者： Haoyu SUN Haiyang MA Li WANG Yang LIU Tian HOU Wenjie TANG qing yu Meiwen AN Meiling WEN Institute of Biomedical Engineering College of Biomedical EngineeringTaiyuan University of TechnologyTaiyuan030024China

Three-dimensional(3D)hydrogel models play a crucial role in tissue engineering for promoting tissue regeneration.A biomimetic microchannel network system in the 3D hydrogel model is necessary for optimal cellular function.This report describes the preparation of a biomimetic hydrogel scaffold with an internal microchannel network,using electrospinning techniques and the sacrificial template method for 3D cell culture.Microchannels and cavities were created within the gelatin methacryloyl(GelMA)hydrogel by sacrificing polyvinyl alcohol(PVA)electrospun fibers(>10µm),resulting in the creation of microvessel-like channels.Mechanical characterizations,swelling properties,and biodegradation analysis were conducted to investigate the feasibility of a biomimetic microchannel network hydrogel scaffold for 3D cell culture applications.Compared to pure GelMA hydrogel,the hydrogel with microchannels promoted cell proliferation,adhesion,and endothelial tube formation.Moreover,the results confirmed that the biomimetic microchannel network scaffold had a major impact on the distribution and arrangement of human umbilical vein endothelial cells(HUVECs)and can enable the formation of artificial microvasculature by the culture of HUVECs and cell media perfusion.

关键词： Biomimetic scaffold Photocrosslinking Microchannel network Tissue engineering Artificial microvascular

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Early adenocarcinoma mixed with a neuroendocrine carcinoma component arising in the gastroesophageal junction: A case report

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 563-570页

作者： yu-qing Cheng Geng-Fang Wang Xiao-Li Zhou Min Lin Xin-Wen Zhang Qin Huang Department of Pathology The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical UniversityChangzhou 213164Jiangsu ProvinceChina Gastroenterology Center The Affiliated Changzhou No.2 People’s Hospital of Nanjing Medical UniversityChangzhou 213164Jiangsu ProvinceChina Graduate School Dalian Medical UniversityDalian 116044Liaoning ProvinceChina Department of Pathology Beth Israel Deaconess Medical Center and Harvard Medical SchoolBostonMA 02215United States

BACKGROUND Early adenocarcinoma mixed with a neuroendocrine carcinoma(NEC)component arising in the gastroesophageal junctional(GEJ)region is rare and even rarer in young patients.Here,we report such a case in a 29-year-old Chinese man.CASE SUMMARY This patient presented to our hospital with a 3-mo history of dysphagia and regurgitation.Upper endoscopy revealed an elevated nodule in the distal esophagus 1.6 cm above the GEJ line,without Barrett’s esophagus or involvement of the gastric cardia.The nodule was completely resected by endoscopic submu-cosal dissection(ESD).Pathological examination confirmed diagnosis of intra-mucosal adenocarcinoma mixed with an NEC component,measuring 1.5 cm.Immunohistochemically,both adenocarcinoma and NEC components were positive for P53 with a Ki67 index of 90%;NEC was positive for synaptophysin and chromogranin.Next-generation sequencing of 196 genes demonstrated a novel germline mutation of the ERCC3 gene in the DNA repair pathway and a germline mutation of the RNF43 gene,a common gastric cancer driver gene,in addition to pathogenic somatic mutations in P53 and CHEK2 genes.The patient was alive without evidence of the disease 36 mo after ESD.CONCLUSION Early adenocarcinoma with an NEC component arising in the distal esophageal side of the GEJ region showed evidence of gastric origin.

关键词： Adenocarcinoma Neuroendocrine carcinoma Gastroesophageal junction Next generation sequencing Case report

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Activatable fluorescent probes for imaging and diagnosis of rheumatoid arthritis

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Military Medical Research 2024年第2期11卷 287-307页

作者： Pan Luo Fu-Qiang Gao Wei Sun Jun-You Li Cheng Wang qing-yu Zhang Zhi-Zhuo Li Peng Xu Department of Joint Surgery Honghui HospitalXi'an Jiaotong UniversityXi'an 710054China Department of Orthopedics China-Japan Friendship HospitalBeijing 100029China Department of Orthopaedic Surgery of the Perelman School of Medicine University of PennsylvaniaPhiladelphiaPA 19104USA School of Mechanical Engineering Sungkyunkwan UniversitySuwon 16419South Korea Department of Orthopaedic Surgery Peking University Third HospitalPeking UniversityBeijing 100191China Department of Orthopedics Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinan 250021China State Key Laboratory of Pharmaceutical Biotechnology Division of Sports Medicine and Adult Reconstructive SurgeryDepartment of Orthopedic SurgeryNanjing Drum Tower Hospitalthe Affiliated Hospital of Nanjing University Medical SchoolNanjing 210008China

Rheumatoid arthritis(RA)is a systemic autoimmune disease that is primarily manifested as synovitis and polyarticular opacity and typically leads to serious joint damage and irreversible disability,thus adversely affecting locomotion ability and life quality.Consequently,good prognosis heavily relies on the early diagnosis and effective therapeutic monitoring of RA.Activatable fluorescent probes play vital roles in the detection and imaging of biomarkers for disease diagnosis and in vivo imaging.Herein,we review the fluorescent probes developed for the detection and imaging of RA biomarkers,namely reactive oxygen/nitrogen species(hypochlorous acid,peroxynitrite,hydroxyl radical,nitroxyl),pH,and cysteine,and address the related challenges and prospects to inspire the design of novel fluorescent probes and the improvement of their performance in RA studies.

关键词： Rheumatoid arthritis Fluorescent probe Imaging Diagnosis Biomarker

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