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Transglutaminase 2 serves as a pathogenic hub gene of KRAS mutant colon cancer based on integrated analysis

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 2074-2090页

作者： Wei-Bin Peng yu-ping Li Yong Zeng Kai Chen First People’s Hospital of Foshan Foshan 528000Guangdong ProvinceChina Department of Radiation Oncology Cancer Hospital of Shantou University Medical CollegeShantou 515031Guangdong ProvinceChina

BACKGROUND Colon cancer is acknowledged as one of the most common malignancies worldwide,ranking third in United States regarding incidence and mortality.Notably,approximately 40%of colon cancer cases harbor oncogenic KRAS mutations,resulting in the continuous activation of epidermal growth factor receptor signaling.AIM To investigate the key pathogenic genes in KRAS mutant colon cancer holds considerable importance.METHODS Weighted gene co-expression network analysis,in combination with additional bioinformatics analysis,were conducted to screen the key factors driving the progression of KRAS mutant colon cancer.Meanwhile,various in vitro experiments were also conducted to explore the biological function of transglutaminase 2(TGM2).RESULTS Integrated analysis demonstrated that TGM2 acted as an independent prognostic factor for progression-free survival.Immunohistochemical analysis on tissue microarrays revealed that TGM2 was associated with an elevated probability of perineural invasion in patients with KRAS mutant colon cancer.Additionally,biological roles of the key gene TGM2 was also assessed,suggesting that the downregulation of TGM2 attenuated the proliferation,invasion,and migration of the KRAS mutant colon cancer cell line.CONCLUSION This study underscores the potential significance of TGM2 in the progression of KRAS mutant colon cancer.This insight not only offers a theoretical foundation for therapeutic approaches but also highlights the need for additional clinical trials and fundamental research to support our preliminary findings.

关键词： Colon cancer KRAS mutation Transglutaminase 2 Weighted gene co-expression network analysis

Serum proteins differentially expressed in gestational diabetes mellitus assessed using isobaric tag for relative and absolute quantitation proteomics

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World Journal of Clinical Cases 2024年第8期12卷 1395-1405页

作者： Wei-Li Cao Cui-ping yu Ling-Li Zhang Department of Women’s Health Care Maternal and Child Health Hospital of Hubei ProvinceWuhan 430070Hubei ProvinceChina Obstetrical Department The First People’s Hospital of Jiangxia District Wuhan City(Union Jiangnan Hospital Huazhong University of Science and Technology)Wuhan 430200Hubei ProvinceC Department of Gynecology Maternal and Child Health Hospital of Hubei ProvinceWuhan 430070Hubei ProvinceChina

BACKGROUND As a well-known fact to the public,gestational diabetes mellitus(GDM)could bring serious risks for both pregnant women and infants.During this important investigation into the linkage between GDM patients and their altered expression in the serum,proteomics techniques were deployed to detect the differentially expressed proteins(DEPs)of in the serum of GDM patients to further explore its pathogenesis,and find out possible biomarkers to forecast GDM occurrence.METHODS Subjects were divided into GDM and normal control groups according to the IADPSG diagnostic criteria.Serum samples were randomly selected from four cases in each group at 24-28 wk of gestation,and the blood samples were identified by applying iTRAQ technology combined with liquid chromatography-tandem mass spectrometry.Key proteins and signaling pathways associated with GDM were identified by bioinformatics analysis,and the expression of key proteins in serum from 12 wk to 16 wk of gestation was further verified using enzyme-linked immunosorbent assay (ELISA).RESULTS Forty-seven proteins were significantly differentially expressed by analyzing the serum samples between the GDMgravidas as well as the healthy ones. Among them, 31 proteins were found to be upregulated notably and the rest16 proteins were downregulated remarkably. Bioinformatic data report revealed abnormal expression of proteinsassociated with lipid metabolism, coagulation cascade activation, complement system and inflammatory responsein the GDM group. ELISA results showed that the contents of RBP4, as well as ANGPTL8, increased in the serumof GDM gravidas compared with the healthy ones, and this change was found to initiate from 12 wk to 16 wk ofgestation.CONCLUSION GDM symptoms may involve abnormalities in lipid metabolism, coagulation cascade activation, complementsystem and inflammatory response. RBP4 and ANGPTL8 are expected to be early predictors of GDM.

关键词： Gestational diabetes mellitus Liquid chromatography-tandem mass spectrometry Isobaric tag for relative and absolute quantitation Proteomics Biomarker

Chemical Composition, Pharmacological Effects and Clinical Applications of Cinobufacini

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Chinese Journal of Integrative Medicine 2024年第4期30卷 366-378页

作者： ZUO Qian XU Ding-qiao yuE Shi-jun FU Rui-jia TANG yu-ping Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility Shaanxi University of Chinese MedicineXi'an(712046)China

Chinese medicine cinobufacini is an extract from the dried skin of Bufo bufo gargarizans Cantor,with active ingredients of bufadienolides and indole alkaloids.With further research and clinical applications,it is found that cinobufacini alone or in combination with other therapeutic methods can play an anti-tumor role by controlling proliferation of tumor cells,promoting apoptosis,inhibiting formation of tumor neovascularization,reversing multidrug resistance,and regulating immune response;it also has the functions of relieving cancer pain and regulating immune function.In this paper,the chemical composition,pharmacological effects,clinical applications,and adverse reactions of cinobufacini are summarized.However,the extraction of monomer components of cinobufacini,the relationship between different mechanisms,and the causes of adverse reactions need to be further studied.Also,high-quality clinical studies should be conducted.

关键词： cinobufacini chemical composition Chinese medicine pharmacological effect clinical application adverse effect

Novel variants in DNAH6 cause male infertility associated with multiple morphological abnormalities of the sperm flagella(MMAF)and ICSI outcomes

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Asian Journal of Andrology 2024年第1期26卷 91-98页

作者： Zhong-Mei Shao yu-Tong Zhu Meng Gu Sen-Chao Guo Hui yu Kuo-Kuo Li Dong-Dong Tang yu-ping Xu Ming-Rong Lv Reproductive Medicine Center Department of Obstetrics and Gynecologythe First Affiliated Hospital of Anhui Medical UniversityHefei 230022China Department of Obstetrics and Gynecology Fuyang Hospital of Anhui Medical UniversityFuyang 236112China NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract(Anhui Medical University) Hefei 230032China Key Laboratory of Population Health Across Life Cycle(Anhui Medical University) Ministry of Education of the People'sRepublicof ChinaHefei 230032China

Variations in the dynein axonemal heavy chain gene,dynein axonemal heavy chain 6(DNAH6),lead to multiple morphological abnormalities of the flagella.Recent studies have reported that these deficiencies may result in sperm head deformation.However,whether DNAH6 is also involved in human acrosome biogenesis remains unknown.The purpose of this study was to investigate DNAH6 gene variants and their potential functions in the formation of defective sperm heads and flagella.Whole-exome sequencing was performed on a cohort of 375 patients with asthenoteratozoospermia from the First Affiliated Hospital of Anhui Medical University(Hefei,China).Hematoxylin and eosin staining,scanning electron microscopy,and transmission electron microscopy were performed to analyze the sperm morphology and ultrastructure.Immunofluorescence staining and Western blot analysis were conducted to examine the effects of genetic variants.We identified three novel deleterious variants in DNAH6 among three unrelated families.The absence of inner dynein arms and radial spokes was observed in the sperm of patients with DNAH6 variants.Additionally,deficiencies in the acrosome,abnormal chromatin compaction,and vacuole-containing sperm heads were observed in these patients with DNAH6 variants.The decreased levels of the component proteins in these defective structures were further confirmed in sperm from patients with DNAH6 variants using Western blot.After intracytoplasmic sperm injection(ICSl)treatment,the partner of one patient with a DNAH6 variant achieved successful pregnancy.Overall,novel variants in DNAH6 genes that contribute to defects in the sperm head and flagella were identified,and the findings indicated Icsl as an effective clinical treatment for such patients.

关键词： asthenoteratospermia DNAH6 intracytoplasmic sperm injection male infertility

C-reactive protein to albumin ratio predict responses to programmed cell death-1 inhibitors in hepatocellular carcinoma patients

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 61-78页

作者： Bai-Bei Li Lei-Jie Chen Shi-Liu Lu Biao Lei Gui-Lin yu Shui-ping yu Department of Hepatobiliary Surgery The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor(Guangxi Medical University) Ministry of EducationNanning 530021Guangxi Zhuang Autonomous RegionChina Guangxi Key Laboratory of Immunology and Metabolism for Liver Diseases Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina Department of Gastroenterology The Second Xiangya Hospital of Central South UniversityNanning 410011Guangxi Zhuang Autonomous RegionChina Department of Emergency The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina

BACKGROUND Over the years,programmed cell death-1(PD-1)inhibitors have been routinely used for hepatocellular carcinoma(HCC)treatment and yielded improved survival outcomes.Nonetheless,significant heterogeneity surrounds the outcomes of most studies.Therefore,it is critical to search for biomarkers that predict the efficacy of PD-1 inhibitors in patients with HCC.AIM To investigate the role of the C-reactive protein to albumin ratio(CAR)in evaluating the efficacy of PD-1 inhibitors for HCC.METHODS The clinical data of 160 patients with HCC treated with PD-1 inhibitors from January 2018 to November 2022 at the First Affiliated Hospital of Guangxi Medical University were retrospectively analyzed.RESULTS The optimal cut-off value for CAR based on progression-free survival(PFS)was determined to be 1.20 using x-tile software.Cox proportional risk model was used to determine the factors affecting prognosis.Eastern Cooperative Oncology Group performance status[hazard ratio(HR)=1.754,95%confidence interval(95%CI)=1.045-2.944,P=0.033],CAR(HR=2.118,95%CI=1.057-4.243,P=0.034)and tumor number(HR=2.932,95%CI=1.246-6.897,P=0.014)were independent prognostic factors for overall survival.CAR(HR=2.730,95%CI=1.502-4.961,P=0.001),tumor number(HR=1.584,95%CI=1.003-2.500,P=0.048)and neutrophil to lymphocyte ratio(HR=1.120,95%CI=1.022-1.228,P=0.015)were independent prognostic factors for PFS.Two nomograms were constructed based on independent prognostic factors.The C-index index and calibration plots confirmed that the nomogram is a reliable risk prediction tool.The ROC curve and decision curve analysis confirmed that the nomogram has a good predictive effect as well as a net clinical benefit.CONCLUSION Overall,we reveal that the CAR is a potential predictor of short-and long-term prognosis in patients with HCC treated with PD-1 inhibitors.If further verified,CAR-based nomogram may increase the number of markers that predict individualized prognosis.

关键词： C-reactive protein to albumin ratio Hepatocellular carcinoma Programmed cell death-1 inhibitors Prognosis Nomogram

Identification of differentially expressed mRNAs as novel predictive biomarkers for gastric cancer diagnosis and prognosis

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1947-1964页

作者： Jian-Wei Zhou Yi-Bing Zhang Zhi-Yang Huang yu-ping yuan Jie Jin Department of Gastroenterology Wenzhou Central HospitalDingli Clinical College of Wenzhou Medical UniversityThe Second Affiliated Hospital of Shanghai UniversityWenzhou 325000Zhejiang ProvinceChina

BACKGROUND Gastric cancer(GC)has a high mortality rate worldwide.Despite significant progress in GC diagnosis and treatment,the prognosis for affected patients still remains unfavorable.AIM To identify important candidate genes related to the development of GC and iden-tify potential pathogenic mechanisms through comprehensive bioinformatics analysis.METHODS The Gene Expression Omnibus database was used to obtain the GSE183136 dataset,which includes a total of 135 GC samples.The limma package in R software was employed to identify differentially expressed genes(DEGs).Thereafter,enrichment analyses of Gene Ontology(GO)terms and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways were performed for the gene modules using the clusterProfile package in R software.The protein-protein interaction(PPI)networks of target genes were constructed using STRING and visualized by Cytoscape software.The common hub genes that emerged in the cohort of DEGs that was retrieved from the GEPIA database were then screened using a Venn Diagram.The expression levels of these overlapping genes in stomach adenocarcinoma samples and non-tumor samples and their association with prognosis in GC patients were also obtained from the GEPIA database and Kaplan-Meier curves.Moreover,real-time quantitative polymerase chain reaction(RT-qPCR)and western blotting were performed to determine the mRNA and protein levels of glutamic-pyruvic transaminase(GPT)in GC and normal immortalized cell lines.In addition,cell viability,cell cycle distribution,migration and invasion were evaluated by cell counting kit-8,flow cytometry and transwell assays.Furthermore,we also conducted a retrospective analysis on 70 GC patients diagnosed and surgically treated in Wenzhou Central Hospital,Dingli Clinical College of Wenzhou Medical University,The Second Affiliated Hospital of Shanghai University between January 2017 to December 2020.The tumor and adjacent normal samples were collected from the patients to determine the potential association between the expression lev

关键词： Gastric cancer Differentially expressed genes Bioinformatics Hub genes Prognosis

Graphdiyne oxide substrate-enhanced peroxidase-mimicking performance of Ru nanoparticles with physiological pH preference

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Nano Research 2024年第3期17卷 1123-1131页

作者： Cong Xu Wenjie Ma Haozhi Wang Leihou Shao Weiqi Li ping yu Lanqun Mao Beijing National Laboratory for Molecular Science Key Laboratory of Analytical Chemistry for Living BiosystemsInstitute of ChemistryChinese Academy of SciencesBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China State Key Laboratory of Marine Resource Utilization in South China Sea School of Materials Science and EngineeringHainan UniversityHaikou 570228China College of Chemistry Beijing Normal UniversityBeijing 100875China

Modulating electronic structure of metal nanoparticles via metal–support interaction has attracted intense interest in the field of catalytic science.However,the roles of supporting substrates in regulating catalytic properties of nanozymes remain elusive.In this study,we find that the use of graphdiyne oxide(GDYO)as the substrate for self-terminating growth of Ru nanoparticles(Ru@GDYO)endows the peroxidase-like activity of Ru nanoparticles with intrinsic physiological pH preference and natural horseradish peroxidase(HRP)comparable performance.Ru nanoparticles electrolessly deposited onto GDYO possess a partially oxidized electronic structure owing to limited charge transfer between Ru and GDYO,contributing to the intrinsic physiological pH preference of the peroxidase-mimicking nanozyme.More importantly,the substrate GDYO plays an influential factor in enhancing catalytic activity,that is,the activity of Ru@GDYO is much higher than that of Ru nanoparticles deposited on other carbon substrates including graphene oxides and graphdiyne.To demonstrate the application of Ru@GDYO nanozyme in neutral solutions,we employ Ru@GDYO with nicotinamide adenine dinucleotide(NAD+)-dependent dehydrogenases in physiological conditions to realize a sustainable cascade reaction by means of forming continuous NAD^(+)/dihydronicotiamide adenine dinucleotide(NADH)recycling.Our finding represents a promising perspective on designing high-performance peroxidase-mimicking nanozymes with broader applicability,raising fundamental understanding of structure–activity relationship,and investigating new applications of nanozymes in biological systems.

关键词： nanozyme graphdiyne reactive oxygen species electroless deposition metal–support interaction

Micropulse transscleral laser therapy for secondary angle-closure glaucoma in nanophthalmos: a case report

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1381-1384页

作者： ping yu Bai-yu Hu yu He Lin Jing Han-Ying Fan Jing Shu Liu-Zhi Zeng Chengdu First People’s Hospital Chengdu 610095Sichuan ProvinceChina Eye School of Chengdu University of TCM Chengdu 610075Sichuan ProvinceChina

Dear Editor,The choice of surgical intervention for nanophthalmos patients with secondary angle-closure glaucoma poses a challenging decision for ophthalmologists.Because nanophthalmos patients who have undergone filtration surgery or other intraocular procedures are more susceptible to severe complications,including choroidal effusion,malignant glaucoma,and explosive choroidal hemorrhage,all of which can lead to vision loss[1].This dilemma is particularly pronounced in patients with shorter axial lengths.Micropulse transscleral laser therapy(M-TLT),also known as micropulse transscleral cyclophotocoagulation(MP-TSCPC),is a nonincisional laser therapy surgery for glaucoma[2].In 2015,Golan and Kurtz[3]were the first to report four patients with secondary angle-closure glaucoma in nanophthalmos with axial lengths ranging between 17 and 19 mm(mean 18 mm)who were successfully treated with M-TLT,and choroidal detachment was observed in all patients(recovery spontaneously in two patients and recovery after systemic steroid treatment in the other two),of which two had a slight decrease in visual acuity.

关键词： glaucoma surgery closure

Age-specific differences in the association between prediabetes and cardiovascular diseases in China:A national cross-sectional study

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World Journal of Diabetes 2024年第2期15卷 240-250页

作者： Shuo Xie Li-ping yu Fei Chen Yao Wang Rui-Fen Deng Xue-Lian Zhang Bo Zhang Department of Endocrinology Chinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100730China Department of Endocrinology China-Japan Friendship HospitalBeijing 100029China

BACKGROUND Cardiovascular disease(CVD)is a leading cause of morbidity and mortality worldwide,the global burden of which is rising.It is still unclear the extent to which prediabetes contributes to the risk of CVD in various age brackets among adults.To develop a focused screening plan and treatment for Chinese adults with prediabetes,it is crucial to identify variations in the connection between prediabetes and the risk of CVD based on age.AIM To examine the clinical features of prediabetes and identify risk factors for CVD in different age groups in China.METHODS The cross-sectional study involved a total of 46239 participants from June 2007 through May 2008.A thorough evaluation was conducted.Individuals with prediabetes were categorized into two groups based on age.Chinese atherosclerotic CVD risk prediction model was employed to evaluate the risk of developing CVD over 10 years.Random forest was established in both age groups.SHapley Additive exPlanation method prioritized the importance of features from the perspective of assessment contribution.RESULTS In total,6948 people were diagnosed with prediabetes in this study.In prediabetes,prevalences of CVD were 5(0.29%)in the younger group and 148(2.85%)in the older group.Overall,11.11%of the younger group and 29.59% of the older group were intermediate/high-risk of CVD for prediabetes without CVD based on the Prediction for ASCVD Risk in China equation in ten years.In the younger age group,the 10-year risk of CVD was found to be more closely linked to family history of CVD rather than lifestyle,whereas in the older age group,resident status was more closely linked.CONCLUSION The susceptibility to CVD is age-specific in newly diagnosed prediabetes.It is necessary to develop targeted approaches for the prevention and management of CVD in adults across various age brackets.

关键词： Age Cardiovascular diseases Prediabetes Risk factors Differences