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Predictive model using four ferroptosis-related genes accurately predicts gastric cancer prognosis

World Journal of Gastrointestinal Oncology 2024年第5期16卷 2018-2037页

作者： Li Wang Wei-hua gong Department of Emergency The Second Affiliated Hospital of Zhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina Department of Surgery The Second Affiliated Hospital Zhejiang University School of MedicineHangzhou 310052Zhejiang ProvinceChina

BACKGROUND Gastric cancer(GC)is a common malignancy of the digestive system.According to global 2018 cancer data,GC has the fifth-highest incidence and the thirdhighest fatality rate among malignant tumors.More than 60%of GC are linked to infection with Helicobacter pylori(H.pylori),a gram-negative,active,microaerophilic,and helical bacterium.This parasite induces GC by producing toxic factors,such as cytotoxin-related gene A,vacuolar cytotoxin A,and outer membrane proteins.Ferroptosis,or iron-dependent programmed cell death,has been linked to GC,although there has been little research on the link between H.pylori infection-related GC and ferroptosis.AIM To identify coregulated differentially expressed genes among ferroptosis-related genes(FRGs)in GC patients and develop a ferroptosis-related prognostic model with discrimination ability.METHODS Gene expression profiles of GC patients and those with H.pylori-associated GC were obtained from The Cancer Genome Atlas and Gene Expression Omnibus(GEO)databases.The FRGs were acquired from the FerrDb database.A ferroptosis-related gene prognostic index(FRGPI)was created using least absolute shrinkage and selection operator–Cox regression.The predictive ability of the FRGPI was validated in the GEO cohort.Finally,we verified the expression of the hub genes and the activity of the ferroptosis inducer FIN56 in GC cell lines and tissues.RESULTS Four hub genes were identified(NOX4,MTCH1,GABARAPL2,and SLC2A3)and shown to accurately predict GC and H.pylori-associated GC.The FRGPI based on the hub genes could independently predict GC patient survival;GC patients in the high-risk group had considerably worse overall survival than did those in the low-risk group.The FRGPI was a significant predictor of GC prognosis and was strongly correlated with disease progression.Moreover,the gene expression levels of common immune checkpoint proteins dramatically increased in the highrisk subgroup of the FRGPI cohort.The hub genes were also confirmed to be highly overexpressed in GC cell line

关键词： Ferroptosis Gastric cancer Helicobacter pylori infection Immune checkpoint protein Prognostic model Ferroptosis-related gene prognostic index

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Treatment of multisystem inflammatory syndrome in children

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World Journal of Pediatrics 2024年第4期20卷 325-339页

作者： Tong Tong Yi-hua Jin Min Wang Fang-Qi gong Department of Cardiology Children's HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthNo.3333 Binsheng RoadHangzhou 310052China

Background Multisystem inflammatory syndrome in children(MIS-C),a relatively uncommon but severe pediatric complication,is associated with coronavirus disease 2019(COVID-19).A variety of treatment approaches,including intravenous immunoglobulins(IVIGs),glucocorticoids(GCs)and biologic agents,such as anakinra and infliximab,have been described for the management of COVID-19-related MIS-C.Anticoagulant therapy is also important.However,a well-developed treatment system has not been established,and many issues remain controversial.Several recently published articles related to the treatment of MIS-C have been released.Hence,in this review,we identified relevant articles published recently and summarized the treatment of MIS-C more comprehensively and systematically.Data sources We reviewed the literature on the treatment of MIS-C through 20 September 2023.The PubMed/Medline,Web of Science,EMBASE,and Cochrane Library databases were searched with the combination of the terms"multisystem inflammatory syndrome","MIS-C","PIMS-TS","therapy","treatment","drug","IVIG","GCs","intravenous immunoglobulin","corticosteroids","biological agent",and"aspirin".Results The severity of MIS-C varies,and different treatment schemes should be used according to the specific condition.Ongoing research and data collection are vital to better understand the pathophysiology and optimal management of MIS-C.Conclusions MIS-Cis a disease involving multiple systems and has great heterogeneity.With the accumulation of additional experience,we have garnered fresh insights into its treatment strategies.However,there remains a critical need for greater standardization in treatment protocols,alongside the pressing necessity for more robust and meticulously conducted studies to deepen our understanding of these protocols.

关键词： Coronavirus disease 2019-Corticosteroids Intravenous immunoglobulin Multisystem inflammatory syndrome in children-Treatment

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Design methodology of a mini-missile considering flight performance and guidance precision

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Journal of Systems Engineering and Electronics 2024年第1期35卷 195-210页

作者： ZHANG Licong gong Chunlin SU hua ANDREA Da Ronch Shaanxi Aerospace Flight Vehicle Design Key Laboratory School of AstronauticsNorthwestern Polytechnical UniversityXi’an 710072China Faculty of Engineering and Physical Sciences University of SouthamptonSouthampton SO171BJUnited Kingdom

The design of mini-missiles(MMs)presents several novel challenges.The stringent mission requirement to reach a target with a certain precision imposes a high guidance precision.The miniaturization of the size of MMs makes the design of the guidance,navigation,and control(GNC)have a larger-thanbefore impact on the main-body design(shape,motor,and layout design)and its design objective,i.e.,flight performance.Pursuing a trade-off between flight performance and guidance precision,all the relevant interactions have to be accounted for in the design of the main body and the GNC system.Herein,a multi-objective and multidisciplinary design optimization(MDO)is proposed.Disciplines pertinent to motor,aerodynamics,layout,trajectory,flight dynamics,control,and guidance are included in the proposed MDO framework.The optimization problem seeks to maximize the range and minimize the guidance error.The problem is solved by using the nondominated sorting genetic algorithm II.An optimum design that balances a longer range with a smaller guidance error is obtained.Finally,lessons learned about the design of the MM and insights into the trade-off between flight performance and guidance precision are given by comparing the optimum design to a design provided by the traditional approach.

关键词： mini-missiles(MMs) guidance navigation and control(GNC)system multi-objective optimization multidisciplinary design optimization(MDO) flight performance guidance precision

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Safflower Yellow Inhibits Progression of Hepatocellular Carcinoma by Modulating Immunological Tolerance via FAK Pathway

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Chinese Journal of Integrative Medicine 2024年第4期30卷 339-347页

作者： JI hua-feng YANG Zi-qiang HAN Jun-jun LI He-fang JIN Zhao-qing CHEN Wei-qing CHEN Fei-hua gong Mou-chun Department of General Surgery First People's Hospital of Hangzhou Lin'an DistrictHangzhou(311300)China

Objective To explore the anti-tumor effect of safflower yellow(SY)against hepatocellular carcinoma(HCC)and the underlying potential mechanism.Methods An in vitro model was established by mixing Luc-Hepa1-6 cells and CD3^(+)CD8^(+)T cells,followed by adding programmed cell death protein 1(PD-1)antibody(Anti-mPD-1)with or without SY.The apoptosis was detected by flow cytometry and the level of inflammatory cytokines was determined by enzyme-linked immunosorbent assay.The protein levels of programmed cell death 1 ligand 1(PD-L1),chemokine ligand(CCL5),C-X-C motif chemokine ligand 10(CXCL10)were measured by Western blot.An in situ animal model was established in mice followed by treatment with anti-mPD-1 with or without SY.Bioluminescence imaging was monitored with an AniView 100 imaging system.To establish the FAK-overexpressed Luc-Hepa1-6 cells,cells were transfected with adenovirus containing pcDNA3.1-FAK for 48 h.Results The fluorescence intensity,apoptotic rate,release of inflammatory cytokines,and CCL5/CXCL10 secretion were dramatically facilitated by anti-mPD-1(P<0.01),accompanied by an inactivation of PD-1/PD-L1 axis,which were extremely further enhanced by SY(P<0.05 or P<0.01).Increased fluorescence intensity,elevated percentage of CD3+CD8+T cells,facilitated release of inflammatory cytokines,inactivated PD-1/PD-L1 axis,and increased CCL5/CXCL10 secretion were observed in Anti-mPD-1 treated mice(P<0.01),which were markedly enhanced by SY(P<0.05 or P<0.01).Furthermore,the enhanced effects of SY on inhibiting tumor cell growth,facilitating apoptosis and inflammatory cytokine releasing,suppressing the PD-1/PD-L1 axis,and inducing the CCL5/CXCL10 secretion in Anti-mPD-1 treated mixture of Luc-Hepa1-6 cells and CD3+CD8+T cells were abolished by FAK overexpression(P<0.01).Conclusion SY inhibited the progression of HCC by mediating immunological tolerance through inhibiting FAK.

关键词： hepatocellular carcinoma safflower yellow Chinese medicine tumor microenvironment programmed cell death protein 1 focal adhesion kinase

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Cobalt-based heterogeneous catalysts for photocatalytic carbon dioxide reduction

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Tungsten 2024年第2期6卷 410-421页

作者： Hong Yuan Jian-hua Mei Yun-Nan gong Di-Chang Zhong Tong-Bu Lu MOE International Joint Laboratory of Materials Microstructure Institute for New Energy Materials and Low Carbon TechnologiesSchool of Materials Science and EngineeringTianjin University of TechnologyTianjin 300384China

Solar light-driven CO_(2)reduction to high value-added chemicals has considered as an outstanding way to solve energy crisis and climate warming.Recently,various photocatalysts have been developed to achieve this reaction.Among them,cobaltbased heterogeneous catalysts have attracted great interest because of their promising performance,product selectivity and stability.Herein,we systematically summarize the research progress of various cobalt-based heterogeneous catalysts for the photoreduction of CO_(2),such as single-atom cobalt,and cobalt-based oxides,nitrides,sulfi des,phosphides,metal-organic frameworks and covalent-organic frameworks.Meanwhile,the advantages and structure-activity relationship of these catalysts in photocatalytic CO_(2)reduction reaction are discussed.Finally,the challenges and prospects for constructing cobaltbased heterogeneous catalysts with high effi ciency are highlighted.

关键词： Cobalt Heterogeneous catalysts CO_(2)reduction Photocatalysis

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HSP110 aggravates ischemia-reperfusion injury after liver transplantation by promoting NF-κB pathway

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 344-352页

作者： Qing-Zhi Hu Zhen-Rui Cao Wei-Xiong Zheng Min-Jie Zhao Jun-hua gong Cong Chen Zhong-Jun Wu Rui Tao Department of Hepatobiliary Surgery Bishan Hospital of Chongqing Medical UniversityChongqing 402760China Department of Cardiothoracic Surgery the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China c Department of Hepatobiliary Surgery the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Hepatobiliary Surgery the Second Affiliated Hospital of Chongqing Medical UniversityChongqing 400010China

Background:Ischemia-reperfusion injury(IRI)poses a significant challenge to liver transplantation(LT).The underlying mechanism primarily involves overactivation of the immune system.Heat shock protein 110(HSP110)functions as a molecular chaperone that helps stabilize protein structures.Methods:An IRI model was established by performing LT on Sprague-Dawley rats,and HSP110 was silenced using siRNA.Hematoxylin-eosin staining,TUNEL,immunohistochemistry,ELISA and liver enzyme analysis were performed to assess IRI following LT.Western blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular changes.Results:Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT(P<0.05).However,when rats were injected with siRNAHSP110,IRI subsequent to LT was notably reduced(P<0.05).Additionally,the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced(P<0.05).Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-κB pathway in the liver(P<0.05).Conclusions:HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer cells.Targeting HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI.

关键词： Ischemia-reperfusion injury Liver transplantation Inflammation HSP110 Heat shock proteins NF-κB

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Low RBC counts predict high on-treatment platelet reactivity in patients undergoing percutaneous coronary intervention and treated with clopidogrel

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The Journal of Biomedical Research 2024年第1期38卷 87-91页

作者： Qian Gu Qin Wang Rui hua Wenhao Zhang Jianzhen Teng Jiazheng Ma Zhou Dong Xiaoxuan gong Chunjian Li Department of Cardiology the First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China

Dear Editor,Cardiovascular disease is the leading cause of deaths worldwide,with coronary artery disease(CAD)accounting for approximately 50%of its mortality.Dual antiplatelet therapy,including aspirin and a P2Y12 inhibitor,is the most important treatment for CAD patients undergoing percutaneous coronary intervention(PCI)to prevent recurrent ischemic events and cardiac death.Clopidogrel is one of the commonly used P2Y12 inhibitors.However,up to 30%of patients treated with a standard dose of clopidogrel present with high on-treatment platelet reactivity(HOPR),which is associated with the increased ischemic risks[1].The causes of HOPR are multifactorial and complex.

关键词： coronary patients mortality

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Non-Cooperative Game of Coordinated Scheduling of Parallel Machine Production and Transportation in Shared Manufacturing

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Computers, Materials & Continua 2023年第7期76卷 239-258页

作者： Peng Liu Ke Xu hua gong School of Management Shenyang University of TechnologyShenyang110870China School of Science Shenyang Ligong UniversityShenyang110159China

Given the challenges of manufacturing resource sharing and competition in the modern manufacturing industry,the coordinated scheduling problem of parallel machine production and transportation is investigated.The problem takes into account the coordination of production and transportation before production as well as the disparities in machine spatial position and performance.A non-cooperative game model is established,considering the competition and self-interest behavior of jobs from different customers for machine resources.The job from different customers is mapped to the players in the game model,the corresponding optional processing machine and location are mapped to the strategy set,and the makespan of the job is mapped to the payoff.Then the solution of the scheduling model is transformed into the Nash equilibrium of the non-cooperative game model.A Nash equilibrium solution algorithm based on the genetic algorithm(NEGA)is designed,and the effective solution of approximate Nash equilibrium for the game model is realized.The fitness function,single-point crossover operator,and mutation operator are derived from the non-cooperative game model’s characteristics and the definition of Nash equilibrium.Rules are also designed to avoid the generation of invalid offspring chromosomes.The effectiveness of the proposed algorithm is demonstrated through numerical experiments of various sizes.Compared with other algorithms such as heuristic algorithms(FCFS,SPT,and LPT),the simulated annealing algorithm(SA),and the particle swarm optimization algorithm(PSO),experimental results show that the proposed NE-GA algorithm has obvious performance advantages.

关键词： Non-cooperative game shared manufacturing parallel machine coordinated production and transportation genetic algorithm

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Defects in phospholipase C zeta cause polyspermy and low fertilization after conventional IVF:not just ICSI failure

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Asian Journal of Andrology 2024年第2期26卷 175-182页

作者： Jian-Fang Che Hui-Xia Wu Si-Cong Zeng Yue-Ren Wu Jing Dai De-hua Cheng Fei gong Guang-Xiu Lu Ge Lin Can Dai School of Medicine Hunan Normal UniversityChangsha 410013China Reproductive and Genetic Hospital of CITIC-Xiangya Changsha 410008China Clinical Research Center for Reproduction and Genetics in Hunan Province Changsha 410078China National Engineering and Research Center of Human Stem Cell Changsha 410205China

Phospholipase C zeta(PLC)is a key sperm-borne oocyte-activating factor that triggers Ca^(2+)oscillations and the subsequent block to polyspermy following gamete fusion.Mutations in PLCZ1,the gene encoding PLCζ,cause male infertility and intracytoplasmic sperm injection(ICSI)fertilization failure;and PLCζ expression and localization patterns are significantly correlated with ICSI fertilization rate(FR).However,in conventional in vitro fertilization(cIVF),whether and how sperm PLCζ affects fertilization remain unclear.Herein,we identified one previously reported and two novel PLCZ1 mutations associated with polyspermy in vitro that are characterized by excessive sperm-zona binding and a delay in pronuclei(PN)formation.Immunofluorescence staining and oocyte activation testing revealed that virtually all spermatozoa from patients lacked functional PLCζ and were thus unable to evoke Ca^(2+) oscillations.ICSI with an artificial oocyte activation treatment successfully rescued the polyspermic phenotype and resulted in a live birth.Furthermore,we analyzed PLCζ in an additional 58 males after cIVF treatment in the Reproductive and Genetic Hospital of CiTiC-Xiangya(Changsha,China)between February 2019 and January 2022.We found that the proportion of spermatozoa that expressed PLCζ was positively correlated with both 2PN rate and total FR.The optimal cutoff value below which males were likely to experience low FR(total FR≤30%)after clVF was 56.7%for the proportion of spermatozoa expressing PLC5.Our study expands the mutation and the phenotypic spectrum of PLCZ1 and further suggests that PLCζ constitutes a promising biomarker for identifying low FRs cases in cIVF due to sperm-related oocyte activation deficiency and that sperm PLCζ analysis may benefit the widermale population and not onlymen with IcsI failure.

关键词： conventional IVF gene variants PLCζ polyspermy

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Deleted in liver cancer 1 suppresses the growth of prostate cancer cells through inhibiting Rho-associated protein kinase pathway

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Asian Journal of Urology 2023年第1期10卷 50-57页

作者： hua gong Kang Chen Lan Zhou Yongchao Jin Weihua Chen Department of Urology Zhoupu HospitalMedicine and Health SciencesShanghai UniversityShanghaiChina Department of Urology Shanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina

Objective:Deleted in liver cancer 1(DLC1)is a GTPase-activating protein that is reported as a suppressor in certain human cancers.However,the detailed biological function of DLC1 is still unclear in human prostate cancer(PCa).In the present study,we aimed to explore the function of DLC1 in PCa cells.Methods:Silencing and overexpression of DLC1 were induced in an androgen-sensitive PCa cell line(LNCaP)using RNA interference and lentiviral vector transduction.The Cell Counting Kit-8 assay was performed to determine cell proliferation.The cell cycle was examined by performing a propidium iodide staining assay.Results:Our results indicated that DLC1 overexpression markedly suppressed the proliferation and cell cycle progression of LNCaP cells.Moreover,DLC1 expression was negatively correlated with Rho-associated protein kinase(ROCK)expression in LNCaP cells.Importantly,this study showed that the ROCK inhibitor Y27632 restored the function of DLC1 in LNCaP cells and reduced the tumorigenicity of LNCaP cells in vivo.Conclusion:Our results indicated that DLC1 overexpression markedly suppressed the proliferation and cell cycle progression of PCa cells and negatively correlated with ROCK expression in PCa cells and tissue.

关键词： Cell cycle Deleted in liver cancer 1 Proliferation Prostate cancer Rho-associated protein kinase

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